Recent Stanford Publications in PubMed
- Ambulatory care after acute kidney injury: an opportunity to improve patient outcomes.Silver SA, Goldstein SL, Harel Z, Harvey A, Rompies EJ, Adhikari NK, Acedillo R, Jain AK, Richardson R, Chan CT, Chertow GM, Bell CM, Wald RCan J Kidney Health Dis
- Bioinformatics analyses of differentially expressed genes associated with bisphosphonate-related osteonecrosis of the jaw in patients with multiple myeloma.Sun J, Wen X, Jin F, Li Y, Hu J, Sun YOnco Targets Ther
- Compliance with clinical pathways for inpatient care in Chinese public hospitals.He XY, Bundorf MK, Gu JJ, Zhou P, Xue DBMC Health Serv Res
- Effect of antepartum meconium staining on perinatal and neonatal outcomes among pregnancies with gastroschisis.Girsen AI, Wallenstein MB, Davis AS, Hintz SR, Desai AK, Mansour T, Merritt TA, Druzin ML, Oshiro BT, Blumenfeld YJJ Matern Fetal Neonatal Med
- Prevalence of Posttraumatic Stress Disorder in Vietnam-Era Women Veterans: The Health of Vietnam-Era Women's Study (HealthVIEWS).Magruder K, Serpi T, Kimerling R, Kilbourne AM, Collins JF, Cypel Y, Frayne SM, Furey J, Huang GD, Gleason T, Reinhard MJ, Spiro A, Kang HJAMA Psychiatry
- Geometrical versus Random β-TCP Scaffolds: Exploring the Effects on Schwann Cell Growth and Behavior.Sweet L, Kang Y, Czisch C, Witek L, Shi Y, Smay J, Plant GW, Yang YPLoS One
- Association of Skin Cancer and Indoor Tanning in Sexual Minority Men and Women.Mansh M, Katz KA, Linos E, Chren MM, Arron SJAMA Dermatol
- An LSC epigenetic signature is largely mutation independent and implicates the HOXA cluster in AML pathogenesis.Jung N, Dai B, Gentles AJ, Majeti R, Feinberg APNat Commun
- The Cutaneous, Net Clinical, and Health Economic Benefits of Advanced Pneumatic Compression Devices in Patients With Lymphedema.Karaca-Mandic P, Hirsch AT, Rockson SG, Ridner SHJAMA Dermatol
- Control of REM sleep by ventral medulla GABAergic neurons.Weber F, Chung S, Beier KT, Xu M, Luo L, Dan YNature
- Freezing of Gait and its Associations in the Early and Advanced Clinical Motor Stages of Parkinson's Disease: A Cross-Sectional Study.Hall JM, Shine JM, O'Callaghan C, Walton CC, Gilat M, Naismith SL, Lewis SJJ Parkinsons Dis
- Air Pollution, Neighbourhood Socioeconomic Factors, and Neural Tube Defects in the San Joaquin Valley of California.Padula AM, Yang W, Carmichael SL, Tager IB, Lurmann F, Hammond SK, Shaw GMPaediatr Perinat Epidemiol
- Frequency of Surgery Cancellations Associated With Myocardial Infarction or Death 6 Months After Coronary Stent Placement.Graham LA, Hollis RH, Richman JS, Hawn MTJAMA Surg
- Calcineurin mediates homeostatic synaptic plasticity by regulating retinoic acid synthesis.Arendt KL, Zhang Z, Ganesan S, Hintze M, Shin MM, Tang Y, Cho A, Graef IA, Chen LProc Natl Acad Sci U S A
- The EARN-Health Trial: protocol for a randomised controlled trial to identify health effects of a financial savings programme among low-income US adults.Basu S, Hamad R, White JS, Modrek S, Rehkopf DH, Cullen MRBMJ Open
- Patient-physician mistrust and violence against physicians in Guangdong Province, China: a qualitative study.Tucker JD, Cheng Y, Wong B, Gong N, Nie JB, Zhu W, McLaughlin MM, Xie R, Deng Y, Huang M, Wong WC, Lan P, Liu H, Miao W, Kleinman A, Patient-Physician Trust Project TeamBMJ Open
- Cell type-specific translational repression of Cyclin B during meiosis in males.Baker CC, Gim BS, Fuller MTDevelopment
- Response to Letter to the Editor re: 'Movement-based subgrouping in low back pain: synergy and divergence in approaches'.Karayannis NV, Jull GA, Hodges PWPhysiotherapy
- Translating the Genome in Time and Space: Specialized Ribosomes, RNA Regulons, and RNA-Binding Proteins.Shi Z, Barna MAnnu Rev Cell Dev Biol
- Glial Fibrillary Acidic Protein-Expressing Glia in the Mouse Lung.Suarez-Mier GB, Buckwalter MSASN Neuro
- The History of Patenting Genetic Material.Sherkow JS, Greely HTAnnu Rev Genet
- Microglial Malfunction: The Third Rail in the Development of Alzheimer's Disease.Mhatre SD, Tsai CA, Rubin AJ, James ML, Andreasson KITrends Neurosci
- Differential Rates of Inadvertent Intravascular Injection during Lumbar Transforaminal Epidural Injections Using Blunt-Tip, Pencil-Point, and Catheter-Extension Needles.Smuck M, Paulus S, Patel A, Demirjian R, Ith MA, Kennedy DJPain Med
- Familial risk of non-Hodgkin lymphoma by sex, relationship, age at diagnosis and histology: A joint study from five Nordic countries.Fallah M, Kharazmi E, Pukkala E, Tretli S, Olsen JH, Tryggvadottir L, Sundquist K, Hemminki KLeukemia
- Metal-to-insulator switching in quantum anomalous Hall states.Kou X, Pan L, Wang J, Fan Y, Choi ES, Lee WL, Nie T, Murata K, Shao Q, Zhang SC, Wang KLNat Commun
- MRI and CT of Low-Grade Fibromyxoid Sarcoma in Children: A Report From Children's Oncology Group Study ARST0332.Sargar K, Kao SC, Spunt SL, Hawkins DS, Parham DM, Coffin C, McCarville MBAJR Am J Roentgenol
- Emergency manual implementation: can brief simulation-based or staff trainings increase familiarity and planned clinical use?Goldhaber-Fiebert SN, Lei V, Nandagopal K, Bereknyei SJt Comm J Qual Patient Saf
- Development and evaluation of an electronic health record-based best-practice discharge checklist for hospital patients.Garg T, Lee JY, Evans KH, Chen J, Shieh LJt Comm J Qual Patient Saf
- The role of the dermatologist in detecting elder abuse and neglect.Danesh MJ, Chang ALJ Am Acad Dermatol
- Creativity is linked to ambition across the bipolar spectrum.Johnson SL, Murray G, Hou S, Staudenmaier PJ, Freeman MA, Michalak EE, CREST.BDJ Affect Disord
- An exploratory study of responses to low-dose lithium in African Americans and Hispanics.Gonzalez Arnold J, Salcedo S, Ketter TA, Calabrese JR, Rabideau DJ, Nierenberg AA, Bazan M, Leon AC, Friedman ES, Iosifescu D, Sylvia LG, Ostacher M, Thase M, Reilly-Harrington NA, Bowden CLJ Affect Disord
- Measuring electric fields and noncovalent interactions using the vibrational stark effect.Fried SD, Boxer SGAcc Chem Res
- Active and latent tuberculosis in Brazilian correctional facilities: a cross-sectional study.Carbone Ada S, Paião DS, Sgarbi RV, Lemos EF, Cazanti RF, Ota MM, Junior AL, Bampi JV, Elias VP, Simionatto S, Motta-Castro AR, Pompílio MA, de Oliveira SM, Ko AI, Andrews JR, Croda JBMC Infect Dis
- Visual manifestations in giant cell arteritis: trend over 5 decades in a population-based cohort.Singh AG, Kermani TA, Crowson CS, Weyand CM, Matteson EL, Warrington KJJ Rheumatol
- Assaying the epigenome in limited numbers of cells.Greenleaf WJMethods
- Glial cell development and function in zebrafish.Lyons DA, Talbot WSCold Spring Harb Perspect Biol
- Studying epithelial morphogenesis in Dictyostelium.Dickinson DJ, Nelson WJ, Weis WIMethods Mol Biol
- Prevalence and characterization of pruritus in epidermolysis bullosa.Danial C, Adeduntan R, Gorell ES, Lucky AW, Paller AS, Bruckner A, Pope E, Morel KD, Levy ML, Li S, Gilmore ES, Lane ATPediatr Dermatol
- Allee effects and species co-existence in an environment where resource abundance varies.M'Gonigle LK, Greenspoon PBJ Theor Biol
- Toxoplasma gondii influences aversive behaviors of female rats in an estrus cycle dependent manner.Golcu D, Gebre RZ, Sapolsky RMPhysiol Behav
- MIDER: network inference with mutual information distance and entropy reduction.Villaverde AF, Ross J, Morán F, Banga JRPLoS One
- JMJD5 regulates cell cycle and pluripotency in human embryonic stem cells.Zhu H, Hu S, Baker JStem Cells
- Phase 1/2 study of ocaratuzumab, an Fc-engineered humanized anti-CD20 monoclonal antibody, in low-affinity FcγRIIIa patients with previously treated follicular lymphoma.Ganjoo KN, de Vos S, Pohlman BL, Flinn IW, Forero-Torres A, Enas NH, Cronier DM, Dang NH, Foon KA, Carpenter SP, Slapak CA, Link BK, Smith MR, Mapara MY, Wooldridge JELeuk Lymphoma
Ambulatory care after acute kidney injury: an opportunity to improve patient outcomes.
Can J Kidney Health Dis. 2015;2:36
Authors: Silver SA, Goldstein SL, Harel Z, Harvey A, Rompies EJ, Adhikari NK, Acedillo R, Jain AK, Richardson R, Chan CT, Chertow GM, Bell CM, Wald R
PURPOSE OF REVIEW: Acute kidney injury (AKI) is an increasingly common problem among hospitalized patients. Patients who survive an AKI-associated hospitalization are at higher risk of de novo and worsening chronic kidney disease, end-stage kidney disease, cardiovascular disease, and death. For hospitalized patients with dialysis-requiring AKI, outpatient follow-up with a nephrologist within 90 days of hospital discharge has been associated with enhanced survival. However, most patients who survive an AKI episode do not receive any follow-up nephrology care. This narrative review describes the experience of two new clinical programs to care for AKI patients after hospital discharge: the Acute Kidney Injury Follow-up Clinic for adults (St. Michael's Hospital and University Health Network, Toronto, Canada) and the AKI Survivor Clinic for children (Cincinnati Children's Hospital, USA).
SOURCES OF INFORMATION: MEDLINE, PubMed, ISI Web of Science.
FINDINGS: These two ambulatory clinics have been in existence for close to two (adult) and four (pediatric) years, and were developed separately and independently in different populations and health systems. The components of both clinics are described, including the target population, referral process, medical interventions, patient education activities, and follow-up schedule. Common elements include targeting patients with KDIGO stage 2 or 3 AKI, regular audits of the inpatient nephrology census to track eligible patients, medication reconciliation, and education on the long-term consequences of AKI.
LIMITATIONS: Despite the theoretical benefits of post-AKI follow-up and the clinic components described, there is no high quality evidence to prove that the interventions implemented in these clinics will reduce morbidity or mortality. Therefore, we also present a plan to evaluate the adult AKI Follow-up Clinic in order to determine if it can improve clinical outcomes compared to patients with AKI who do not receive follow-up care.
IMPLICATIONS: Follow-up of AKI survivors is low, and this review describes two different clinics that care for patients who survive an AKI episode. We believe that sharing the experiences of the AKI Follow-up Clinic and AKI Survivor Clinic provide physicians with a feasible framework to implement their own clinics, which may help AKI patients receive outpatient care commensurate with their high risk status.
PMID: 26445676 [PubMed - as supplied by publisher]
Bioinformatics analyses of differentially expressed genes associated with bisphosphonate-related osteonecrosis of the jaw in patients with multiple myeloma.
Onco Targets Ther. 2015;8:2681-2688
Authors: Sun J, Wen X, Jin F, Li Y, Hu J, Sun Y
PURPOSE: This study aimed to explore the molecular mechanisms associated with bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) in patients with multiple myeloma (MM).
METHODS: The gene expression profile GSE7116 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) from eleven patients with ONJ resulting from MM treated with BPs (ONJBPs) and ten MM patients without ONJ treated with BPs (MMBPs) were analyzed. Gene ontology (GO) and pathway enrichment analyses of DEGs were performed, followed by functional annotation and protein-protein interaction network construction. Finally, sub-network modules were constructed and analyzed.
RESULTS: A total of 166 up- and 473 down-regulated DEGs were identified. The up-regulated DEGs were enriched in pathways related to cancer, and the down-regulated DEGs were enriched in pathways related to the immune system. Moreover, the GO terms enriched by the up-regulated DEGs were associated with misfolded proteins, and the down-regulated DEGs were associated with immune responses. After functional annotation, 16 transcription factors were identified, including X-box binding protein 1 (XBP1). In protein-protein interaction network analysis, tumor necrosis factor (TNF) and interleukin 1, beta (IL1B) had higher connectivity degrees. Among the constructed sub-network modules, module 1 was the best one, and DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5) was a hub gene. The DEGs in module 1 were mainly enriched in GO terms related to RNA splicing.
CONCLUSION: DEGs of ONJ were mainly enriched in pathways related to the immune system and RNA splicing. DEGs such as TNF, ILB1, DDX5, and XBP1 may be the potential targets of ONJ treatment.
PMID: 26445550 [PubMed - as supplied by publisher]
Compliance with clinical pathways for inpatient care in Chinese public hospitals.
BMC Health Serv Res. 2015;15(1):459
Authors: He XY, Bundorf MK, Gu JJ, Zhou P, Xue D
BACKGROUND: The National Health and Family Planning Commission of China has issued more than 400 clinical pathways to improve the effectiveness and efficiency of medical care delivered by public hospitals in China. The aim of our study is to determine whether patient care is compliant with national clinical pathways in public general hospitals of Pudong New Area in Shanghai.
METHODS: We identified the clinical pathways established by the National Health and Family Planning Commission of China for 5 common conditions (community-acquired pneumonia, acute myocardial infarction (AMI), heart failure, cesarean section, type-2 diabetes). We randomly selected patients with each condition admitted to one of 7 public general hospitals in Pudong New Area in China in January, 2013. We identified key process indicators (KPIs) for each pathway and, based on chart review for each patient, determined whether the patient's care was compliant for each indicator. We calculated the proportion of care which was compliant with clinical pathways for each indicator, the average proportion of indicators that were met for each patient, and the proportion of patients whose care was compliant for all measures. For selected indicators, we compared compliance rates among hospitals in our study with those from other countries.
RESULTS: Average compliance rates across the KPIs for each condition ranged from 61 % for AMI to 89 % for pneumonia. The percent of patient receiving fully compliant care ranged from 0 for AMI and heart failure to 39 % for pneumonia. Compared to the compliance rate for process indicators in the hospitals of other countries, some rates in the hospitals that we audited were higher, but some were lower.
CONCLUSIONS: Few patients received care that complied with all the pathways for each condition. The reasons for low compliance with national clinical pathways and how to improve clinical quality in public hospitals of China need to be further explored.
PMID: 26445427 [PubMed - as supplied by publisher]
Effect of antepartum meconium staining on perinatal and neonatal outcomes among pregnancies with gastroschisis.
J Matern Fetal Neonatal Med. 2015 Oct 7;:1-5
Authors: Girsen AI, Wallenstein MB, Davis AS, Hintz SR, Desai AK, Mansour T, Merritt TA, Druzin ML, Oshiro BT, Blumenfeld YJ
OBJECTIVE: To investigate the association between meconium staining and perinatal and neonatal outcomes in pregnancies with gastroschisis.
METHODS: Retrospective analysis of infants with prenatally diagnosed gastroschisis born in two academic medical centers between 2008 and 2013. Neonatal outcomes of deliveries with and without meconium staining were compared. Primary outcome was defined as any of the following: neonatal sepsis, prolonged mechanical ventilation, bowel atresia or death. Secondary outcomes were preterm delivery, preterm-premature rupture of membranes (PPROM) and prolonged hospital length of stay.
RESULTS: One hundred and eight infants with gastroschisis were included of which 56 (52%) had meconium staining at delivery. Infants with meconium staining had a lower gestational age at delivery (36.3 (±1.4) versus 37.0 (±1.2) weeks, p = 0.007), and a higher rate of PPROM (25% versus 8%, p = 0.03) than infants without meconium. Meconium staining was not significantly associated with the primary composite outcome or with any of its components. After adjustments, meconium staining remained significantly associated with preterm delivery at <36 weeks [odds ratio OR = 4.0, 95% confidence intervals (CI): 1.5-11.4] and PPROM (OR = 3.8, 95%CI: 1.2-14.5).
CONCLUSIONS: Among infants with gastroschisis, meconium staining was associated with prematurity and PPROM. No significant increase in other adverse neonatal outcomes was seen among infants with meconium staining, suggesting a limited prognostic value of this finding.
PMID: 26445130 [PubMed - as supplied by publisher]
Prevalence of Posttraumatic Stress Disorder in Vietnam-Era Women Veterans: The Health of Vietnam-Era Women's Study (HealthVIEWS).
JAMA Psychiatry. 2015 Oct 7;:1-8
Authors: Magruder K, Serpi T, Kimerling R, Kilbourne AM, Collins JF, Cypel Y, Frayne SM, Furey J, Huang GD, Gleason T, Reinhard MJ, Spiro A, Kang H
Importance: Many Vietnam-era women veterans served in or near war zones and may have experienced stressful or traumatic events during their service. Although posttraumatic stress disorder (PTSD) is well studied among men who served in Vietnam, no major epidemiologic investigation of PTSD among women has been performed.
Objectives: To assess (1) the onset and prevalence of lifetime and current PTSD for women who served during the Vietnam era, stratified by wartime location (Vietnam, near Vietnam, or the United States), and (2) the extent to which wartime location was associated with PTSD, with adjustment for demographics, service characteristics, and wartime exposures.
Design, Setting, and Participants: Survey of 8742 women who were active-duty military personnel in the US Armed Forces at any time from July 4, 1965, through March 28, 1973, and alive as of survey receipt as part of Department of Veterans Affairs Cooperative Study 579, HealthVIEWS. Data were obtained from mailed and telephone surveys from May 16, 2011, through August 5, 2012, and analyzed from June 26, 2013, through July 30, 2015.
Main Outcomes and Measures: Lifetime and current PTSD as measured by the PTSD module of the Composite International Diagnostic Interview, version 3.0; onset of PTSD; and wartime experiences as measured by the Women's Wartime Exposure Scale-Revised.
Results: Among the 4219 women (48.3%) who completed the survey and a telephone interview, the weighted prevalence (95% CI) of lifetime PTSD was 20.1% (18.3%-21.8%), 11.5% (9.1%-13.9%), and 14.1% (12.4%-15.8%) for the Vietnam, near-Vietnam, and US cohorts, respectively. The weighted prevalence (95% CI) of current PTSD was 15.9% (14.3%-17.5%), 8.1% (6.0%-10.2%), and 9.1% (7.7%-10.5%) for the 3 cohorts, respectively. Few cases of PTSD among the Vietnam or near-Vietnam cohorts were attributable to premilitary onset (weighted prevalence, 2.9% [95% CI, 2.2%-3.7%] and 2.9% [95% CI, 1.7%-4.2%], respectively). Unadjusted models for lifetime and current PTSD indicated that women who served in Vietnam were more likely to meet PTSD criteria than women who mainly served in the United States (odds ratio [OR] for lifetime PTSD, 1.53 [95% CI, 1.28-1.83]; OR for current PTSD, 1.89 [95% CI, 1.53-2.33]). When we adjusted for wartime exposures, serving in Vietnam or near Vietnam did not increase the odds of having current PTSD (adjusted ORs, 1.05 [95% CI, 0.75-1.46] and 0.77 [95% CI, 0.52-1.14], respectively).
Conclusions and Relevance: The prevalence of PTSD for the Vietnam cohort was higher than previously documented. Vietnam service significantly increased the odds of PTSD relative to US service; this effect appears to be associated with wartime exposures, especially sexual discrimination or harassment and job performance pressures. Results suggest long-lasting mental health effects of Vietnam-era service among women veterans.
PMID: 26445103 [PubMed - as supplied by publisher]
Geometrical versus Random β-TCP Scaffolds: Exploring the Effects on Schwann Cell Growth and Behavior.
PLoS One. 2015;10(10):e0139820
Authors: Sweet L, Kang Y, Czisch C, Witek L, Shi Y, Smay J, Plant GW, Yang Y
Numerous studies have demonstrated that Schwann cells (SCs) play a role in nerve regeneration; however, their role in innervating a bioceramic scaffold for potential application in bone regeneration is still unknown. Here we report the cell growth and functional behavior of SCs on β-tricalcium phosphate (β-TCP) scaffolds arranged in 3D printed-lattice (P-β-TCP) and randomly-porous, template-casted (N-β-TCP) structures. Our results indicate that SCs proliferated well and expressed the phenotypic markers p75LNGFR and the S100-β subunit of SCs as well as displayed growth morphology on both scaffolds, but SCs showed spindle-shaped morphology with a significant degree of SCs alignment on the P-β-TCP scaffolds, seen to a lesser degree in the N-β-TCP scaffold. The gene expressions of nerve growth factor (β-ngf), neutrophin-3 (nt-3), platelet-derived growth factor (pdgf-bb), and vascular endothelial growth factor (vegf-a) were higher at day 7 than at day 14. While no significant differences in protein secretion were measured between these last two time points, the scaffolds promoted the protein secretion at day 3 compared to that on the cell culture plates. These results together imply that the β-TCP scaffolds can support SC cell growth and that the 3D-printed scaffold appeared to significantly promote the alignment of SCs along the struts. Further studies are needed to investigate the early and late stage relationship between gene expression and protein secretion of SCs on the scaffolds with refined characteristics, thus better exploring the potential of SCs to support vascularization and innervation in synthetic bone grafts.
PMID: 26444999 [PubMed - as supplied by publisher]
Association of Skin Cancer and Indoor Tanning in Sexual Minority Men and Women.
JAMA Dermatol. 2015 Oct 7;:1-9
Authors: Mansh M, Katz KA, Linos E, Chren MM, Arron S
Importance: Skin cancer, the most common cancer in the United States, is highly associated with outdoor and indoor tanning behaviors. Although indoor tanning has been suggested to be more common among sexual minority (self-reported as homosexual, gay, or bisexual) men compared with heterosexual men, whether rates of skin cancer vary by sexual orientation is unknown.
Objective: To investigate whether skin cancer prevalence and indoor tanning behaviors vary by sexual orientation in the general population.
Design, Setting, and Participants: We performed a cross-sectional study using data from the 2001, 2003, 2005, and 2009 California Health Interview Surveys (CHISs) and the 2013 National Health Interview Survey (NHIS) of population-based samples of the California and US noninstitutionalized civilian population. Participants included 192 575 men and women 18 years or older who identified as heterosexual or a sexual minority.
Main Outcomes and Measures: Self-reported lifetime history of skin cancer and 12-month history of indoor tanning.
Results: The study included 78 487 heterosexual men, 3083 sexual minority men, 107 976 heterosexual women, and 3029 sexual minority women. Sexual minority men were more likely than heterosexual men to report having skin cancer (2001-2005 CHISs: adjusted odds ratio [aOR], 1.56; 95% CI, 1.18-2.06, P < .001; 2013 NHIS: aOR, 2.13; 95% CI, 1.14-3.96, P = .02) and having tanned indoors (2009 CHIS: aOR, 5.80; 95% CI, 2.90-11.60, P < .001; 2013 NHIS: aOR, 3.16; 95% CI, 1.77-5.64, P < .001). Sexual minority women were less likely than heterosexual women to report having had nonmelanoma skin cancer (2001-2005 CHIS: aOR, 0.56; 95% CI, 0.37-0.86, P = .008) and having tanned indoors (2009 CHIS: aOR, 0.43; 95% CI, 0.20-0.92, P = .03; 2013 NHIS: aOR, 0.46; 95% CI, 0.26-0.81, P = .007).
Conclusions and Relevance: Sexual minority men indoor tan more frequently and report higher rates of skin cancer than heterosexual men. Primary and secondary prevention efforts targeted at sexual minority men might reduce risk factors for, and consequences of, skin cancer.
PMID: 26444580 [PubMed - as supplied by publisher]
An LSC epigenetic signature is largely mutation independent and implicates the HOXA cluster in AML pathogenesis.
Nat Commun. 2015;6:8489
Authors: Jung N, Dai B, Gentles AJ, Majeti R, Feinberg AP
Acute myeloid leukaemia (AML) is characterized by subpopulations of leukaemia stem cells (LSCs) that are defined by their ability to engraft in immunodeficient mice. Here we show an LSC DNA methylation signature, derived from xenografts and integration with gene expression that is comprised of 71 genes and identifies a key role for the HOXA cluster. Most of the genes are epigenetically regulated independently of underlying mutations, although several are downstream targets of epigenetic modifier genes mutated in AML. The LSC epigenetic signature is associated with poor prognosis independent of known risk factors such as age and cytogenetics. Analysis of early haematopoietic progenitors from normal individuals reveals two distinct clusters of AML LSC resembling either lymphoid-primed multipotent progenitors or granulocyte/macrophage progenitors. These results provide evidence for DNA methylation variation between AML LSCs and their blast progeny, and identify epigenetically distinct subgroups of AML likely reflecting the cell of origin.
PMID: 26444494 [PubMed - as supplied by publisher]
The Cutaneous, Net Clinical, and Health Economic Benefits of Advanced Pneumatic Compression Devices in Patients With Lymphedema.
JAMA Dermatol. 2015 Oct 7;:1-7
Authors: Karaca-Mandic P, Hirsch AT, Rockson SG, Ridner SH
Importance: The prevalence and clinical burden of lymphedema is known to be increasing. Nevertheless, evidence-based comparative effectiveness data regarding lymphedema therapeutic interventions have been poor.
Objective: To examine the impact of an advanced pneumatic compression device (APCD) on cutaneous and other clinical outcomes and health economic costs in a representative privately insured population of lymphedema patients.
Design, Setting, and Participants: Retrospective analysis of a deidentified private insurance database from 2007 through 2013, and multivariate regression analysis comparing outcomes for the 12 months before and after APCD purchase, adjusting for baseline patient characteristics. Patients with lymphedema who received an APCD who were commercially insured and Medicare managed care enrollees from a large, national US managed care health insurer. The study population was evaluated as cancer-related and non-cancer-related lymphedema cohorts.
Intervention: Receipt of an APCD.
Main Outcomes and Measures: Rates of cellulitis, use of lymphedema-related manual therapy, outpatient hospital visits, and inpatient hospitalizations. Lymphedema-related direct costs were measured for home health care, hospital outpatient care, office visits, emergency department use, and inpatient care.
Results: The study sample included 718 patients (374 in the cancer cohort and 344 in the noncancer cohort). In both cohorts, use of an APCD was associated with similar reductions in adjusted rates of cellulitis episodes (from 21.1% to 4.5% in the cancer cohort and 28.8% to 7.3% in the noncancer cohort; P < .001 for both), lymphedema-related manual therapy (from 35.6% to 24.9%in the cancer cohort and 32.3% to 21.2% in the noncancer cohort; P < .001 for both), and outpatient visits (from 58.6% to 41.4% in the cancer cohort and 52.6% to 31.4% in the noncancer cohort; P < .001 for both). Among the cancer cohort, total lymphedema-related costs per patient, excluding medical equipment costs, were reduced by 37% (from $2597 to $1642, P = .002). The corresponding decline in costs for the noncancer cohort was 36% (from $2937 to $1883, P = .007).
Conclusions and Relevance: The study found an association between significant reductions in episodes of cellulitis (cancer vs noncancer cohorts) and outpatient care and costs of APCD acquisition within a 1-year time frame in patients with both cancer-related and non-cancer-related lymphedema.
PMID: 26444458 [PubMed - as supplied by publisher]
Control of REM sleep by ventral medulla GABAergic neurons.
Nature. 2015 Oct 7;
Authors: Weber F, Chung S, Beier KT, Xu M, Luo L, Dan Y
Rapid eye movement (REM) sleep is a distinct brain state characterized by activated electroencephalogram and complete skeletal muscle paralysis, and is associated with vivid dreams. Transection studies by Jouvet first demonstrated that the brainstem is both necessary and sufficient for REM sleep generation, and the neural circuits in the pons have since been studied extensively. The medulla also contains neurons that are active during REM sleep, but whether they play a causal role in REM sleep generation remains unclear. Here we show that a GABAergic (γ-aminobutyric-acid-releasing) pathway originating from the ventral medulla powerfully promotes REM sleep in mice. Optogenetic activation of ventral medulla GABAergic neurons rapidly and reliably initiated REM sleep episodes and prolonged their durations, whereas inactivating these neurons had the opposite effects. Optrode recordings from channelrhodopsin-2-tagged ventral medulla GABAergic neurons showed that they were most active during REM sleep (REMmax), and during wakefulness they were preferentially active during eating and grooming. Furthermore, dual retrograde tracing showed that the rostral projections to the pons and midbrain and caudal projections to the spinal cord originate from separate ventral medulla neuron populations. Activating the rostral GABAergic projections was sufficient for both the induction and maintenance of REM sleep, which are probably mediated in part by inhibition of REM-suppressing GABAergic neurons in the ventrolateral periaqueductal grey. These results identify a key component of the pontomedullary network controlling REM sleep. The capability to induce REM sleep on command may offer a powerful tool for investigating its functions.
PMID: 26444238 [PubMed - as supplied by publisher]
Freezing of Gait and its Associations in the Early and Advanced Clinical Motor Stages of Parkinson's Disease: A Cross-Sectional Study.
J Parkinsons Dis. 2015 Oct 1;
Authors: Hall JM, Shine JM, O'Callaghan C, Walton CC, Gilat M, Naismith SL, Lewis SJ
BACKGROUND: Freezing of gait is a common disabling symptom of Parkinson's disease (PD) with limited treatment options. The pathophysiological mechanisms of freezing behaviour are still contentious.
OBJECTIVE: To investigate the prevalence of freezing of gait and its associations with increasing disease severity to gain a better understanding of the underlying pathophysiology.
METHODS: This exploratory study included 389 idiopathic PD patients, divided into four groups; early and advanced PD with freezing of gait, and early and advanced PD without freezing of gait. Motor, cognitive and affective symptoms, REM sleep behaviour disorder and autonomic function were assessed.
RESULTS: Regardless of disease stage, patients with freezing of gait had more severe motor symptoms and a predominant non-tremor phenotype. In the early stages, freezers had a selective impairment in executive function and had more marked REM sleep behaviour disorder. Autonomic disturbances were not associated with freezing of gait across early or advanced disease stages.
CONCLUSION: These findings support the notion that impairments across the frontostriatal pathways are intricately linked to the pathophysiology underlying freezing of gait across all stages of PD. Features of REM sleep behaviour disorder suggest a contribution to freezing from brainstem pathology but this does not extend to more general autonomic dysfunction.
PMID: 26444088 [PubMed - as supplied by publisher]
Air Pollution, Neighbourhood Socioeconomic Factors, and Neural Tube Defects in the San Joaquin Valley of California.
Paediatr Perinat Epidemiol. 2015 Nov;29(6):536-545
Authors: Padula AM, Yang W, Carmichael SL, Tager IB, Lurmann F, Hammond SK, Shaw GM
BACKGROUND: Environmental pollutants and neighbourhood socioeconomic factors have been associated with neural tube defects, but the potential impact of interaction between ambient air pollution and neighbourhood socioeconomic factors on the risks of neural tube defects is not well understood.
METHODS: We used data from the California Center of the National Birth Defects Study and the Children's Health and Air Pollution Study to investigate whether associations between air pollutant exposure in early gestation and neural tube defects were modified by neighbourhood socioeconomic factors in the San Joaquin Valley of California, 1997-2006. There were 5 pollutant exposures, 3 outcomes, and 9 neighbourhood socioeconomic factors included for a total of 135 investigated associations. Estimates were adjusted for maternal race-ethnicity, education, and multivitamin use.
RESULTS: We present below odds ratios (ORs) that exclude 1 and a chi-square test of homogeneity P-value of <0.05. We observed increased odds of spina bifida comparing the highest to lowest quartile of particulate matter <10 μm (PM10 ) among those living in a neighbourhood with: (i) median household income of less than $30 000 per year [OR 5.1, 95% confidence interval (CI) 1.7, 15.3]; (ii) more than 20% living below the federal poverty level (OR 2.6, 95% CI 1.1, 6.0); and (iii) more than 30% with less than or equal to a high school education (OR 3.2, 95% CI 1.4, 7.4). The ORs were not statistically significant among those higher socioeconomic status (SES) neighbourhoods.
CONCLUSIONS: Our results demonstrate effect modification by neighbourhood socioeconomic factors in the association of particulate matter and neural tube defects in California.
PMID: 26443985 [PubMed - as supplied by publisher]
Frequency of Surgery Cancellations Associated With Myocardial Infarction or Death 6 Months After Coronary Stent Placement.
JAMA Surg. 2015 Oct 7;:1-3
Authors: Graham LA, Hollis RH, Richman JS, Hawn MT
PMID: 26443936 [PubMed - as supplied by publisher]
Calcineurin mediates homeostatic synaptic plasticity by regulating retinoic acid synthesis.
Proc Natl Acad Sci U S A. 2015 Oct 6;
Authors: Arendt KL, Zhang Z, Ganesan S, Hintze M, Shin MM, Tang Y, Cho A, Graef IA, Chen L
Homeostatic synaptic plasticity is a form of non-Hebbian plasticity that maintains stability of the network and fidelity for information processing in response to prolonged perturbation of network and synaptic activity. Prolonged blockade of synaptic activity decreases resting Ca(2+) levels in neurons, thereby inducing retinoic acid (RA) synthesis and RA-dependent homeostatic synaptic plasticity; however, the signal transduction pathway that links reduced Ca(2+)-levels to RA synthesis remains unknown. Here we identify the Ca(2+)-dependent protein phosphatase calcineurin (CaN) as a key regulator for RA synthesis and homeostatic synaptic plasticity. Prolonged inhibition of CaN activity promotes RA synthesis in neurons, and leads to increased excitatory and decreased inhibitory synaptic transmission. These effects of CaN inhibitors on synaptic transmission are blocked by pharmacological inhibitors of RA synthesis or acute genetic deletion of the RA receptor RARα. Thus, CaN, acting upstream of RA, plays a critical role in gating RA signaling pathway in response to synaptic activity. Moreover, activity blockade-induced homeostatic synaptic plasticity is absent in CaN knockout neurons, demonstrating the essential role of CaN in RA-dependent homeostatic synaptic plasticity. Interestingly, in GluA1 S831A and S845A knockin mice, CaN inhibitor- and RA-induced regulation of synaptic transmission is intact, suggesting that phosphorylation of GluA1 C-terminal serine residues S831 and S845 is not required for CaN inhibitor- or RA-induced homeostatic synaptic plasticity. Thus, our study uncovers an unforeseen role of CaN in postsynaptic signaling, and defines CaN as the Ca(2+)-sensing signaling molecule that mediates RA-dependent homeostatic synaptic plasticity.
PMID: 26443861 [PubMed - as supplied by publisher]
The EARN-Health Trial: protocol for a randomised controlled trial to identify health effects of a financial savings programme among low-income US adults.
BMJ Open. 2015;5(10):e009366
Authors: Basu S, Hamad R, White JS, Modrek S, Rehkopf DH, Cullen MR
INTRODUCTION: A theory within the social epidemiology field is that financial stress related to having inadequate financial savings may contribute to psychological stress, poor mental health and poor health-related behaviours among low-income US adults. Our objective is to test whether an intervention that encourages financial savings among low-income US adults improves health behaviours and mental health.
METHODS AND ANALYSIS: A parallel group two-arm controlled superiority trial will be performed in which 700 participants will be randomised to the intervention or a wait list. The intervention arm will be provided an online Individual Development Account (IDA) for 6 months, during which participants receive a $5 incentive (£3.2, €4.5) for every month they save $20 in their account (£12.8, €18), and an additional $5 if they save $20 for two consecutive months. Both groups will be provided links to standard online financial counselling materials. Online surveys in months 0 (prior to randomisation), 6 and 12 (6 months postintervention) will assess self-reported health behaviours and mental health among participants in both arms. The surveys items were tested previously in the US Centers for Disease Control and Prevention national health interviews and related health studies, including self-reported overall health, health-related quality of life, alcohol and tobacco use, depression symptoms, financial stress, optimism and locus of control, and spending and savings behaviours. Trial data will be analysed on an intent-to-treat basis.
ETHICS AND DISSEMINATION: This protocol was approved by the Institutional Review Board of Stanford University (Protocol ID: 30641). The findings of the trial will be disseminated through peer-reviewed publication.
TRIAL REGISTRATION NUMBER: Identifier NCT02185612; Pre-results.
PMID: 26443663 [PubMed - in process]
Patient-physician mistrust and violence against physicians in Guangdong Province, China: a qualitative study.
BMJ Open. 2015;5(10):e008221
Authors: Tucker JD, Cheng Y, Wong B, Gong N, Nie JB, Zhu W, McLaughlin MM, Xie R, Deng Y, Huang M, Wong WC, Lan P, Liu H, Miao W, Kleinman A, Patient-Physician Trust Project Team
OBJECTIVE: To better understand the origins, manifestations and current policy responses to patient-physician mistrust in China.
DESIGN: Qualitative study using in-depth interviews focused on personal experiences of patient-physician mistrust and trust.
SETTING: Guangdong Province, China.
PARTICIPANTS: One hundred and sixty patients, patient family members, physicians, nurses and hospital administrators at seven hospitals varying in type, geography and stages of achieving goals of health reform. These interviews included purposive selection of individuals who had experienced both trustful and mistrustful patient-physician relationships.
RESULTS: One of the most prominent forces driving patient-physician mistrust was a patient perception of injustice within the medical sphere, related to profit mongering, knowledge imbalances and physician conflicts of interest. Individual physicians, departments and hospitals were explicitly incentivised to generate revenue without evaluation of caregiving. Physicians did not receive training in negotiating medical disputes or humanistic principles that underpin caregiving. Patient-physician mistrust precipitated medical disputes leading to the following outcomes: non-resolution with patient resentment towards physicians; violent resolution such as physical and verbal attacks against physicians; and non-violent resolution such as hospital-mediated dispute resolution. Policy responses to violence included increased hospital security forces, which inadvertently fuelled mistrust. Instead of encouraging communication that facilitated resolution, medical disputes sometimes ignited a vicious cycle leading to mob violence. However, patient-physician interactions at one hospital that has implemented a primary care model embodying health reform goals showed improved patient-physician trust.
CONCLUSIONS: The blind pursuit of financial profits at a systems level has eroded patient-physician trust in China. Restructuring incentives, reforming medical education and promoting caregiving are pathways towards restoring trust. Assessing and valuing the quality of caregiving is essential for transitioning away from entrenched profit-focused models. Moral, in addition to regulatory and legal, responses are urgently needed to restore trust.
PMID: 26443652 [PubMed - in process]
Cell type-specific translational repression of Cyclin B during meiosis in males.
Development. 2015 Oct 1;142(19):3394-402
Authors: Baker CC, Gim BS, Fuller MT
The unique cell cycle dynamics of meiosis are controlled by layers of regulation imposed on core mitotic cell cycle machinery components by the program of germ cell development. Although the mechanisms that regulate Cdk1/Cyclin B activity in meiosis in oocytes have been well studied, little is known about the trans-acting factors responsible for developmental control of these factors in male gametogenesis. During meiotic prophase in Drosophila males, transcript for the core cell cycle protein Cyclin B1 (CycB) is expressed in spermatocytes, but the protein does not accumulate in spermatocytes until just before the meiotic divisions. Here, we show that two interacting proteins, Rbp4 and Fest, expressed at the onset of spermatocyte differentiation under control of the developmental program of male gametogenesis, function to direct cell type- and stage-specific repression of translation of the core G2/M cell cycle component cycB during the specialized cell cycle of male meiosis. Binding of Fest to Rbp4 requires a 31-amino acid region within Rbp4. Rbp4 and Fest are required for translational repression of cycB in immature spermatocytes, with Rbp4 binding sequences in a cell type-specific shortened form of the cycB 3' UTR. Finally, we show that Fest is required for proper execution of meiosis I.
PMID: 26443637 [PubMed - in process]
Response to Letter to the Editor re: 'Movement-based subgrouping in low back pain: synergy and divergence in approaches'.
Physiotherapy. 2015 Aug 13;
Authors: Karayannis NV, Jull GA, Hodges PW
PMID: 26443556 [PubMed - as supplied by publisher]
Translating the Genome in Time and Space: Specialized Ribosomes, RNA Regulons, and RNA-Binding Proteins.
Annu Rev Cell Dev Biol. 2015 Oct 5;
Authors: Shi Z, Barna M
A central question in cell and developmental biology is how the information encoded in the genome is differentially interpreted to generate a diverse array of cell types. A growing body of research on posttranscriptional gene regulation is revealing that both global protein synthesis rates and the translation of specific mRNAs are highly specialized in different cell types. How this exquisite translational regulation is achieved is the focus of this review. Two levels of regulation are discussed: the translation machinery and cis-acting elements within mRNAs. Recent evidence shows that the ribosome itself directs how the genome is translated in time and space and reveals surprising functional specificity in individual components of the core translation machinery. We are also just beginning to appreciate the rich regulatory information embedded in the untranslated regions of mRNAs, which direct the selective translation of transcripts. These hidden RNA regulons may interface with a myriad of RNA-binding proteins and specialized translation machinery to provide an additional layer of regulation to how transcripts are spatiotemporally expressed. Understanding this largely unexplored world of translational codes hardwired in the core translation machinery is an exciting new research frontier fundamental to our understanding of gene regulation, organismal development, and evolution. Expected final online publication date for the Annual Review of Cell and Developmental Biology Volume 31 is November 7, 2015. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
PMID: 26443190 [PubMed - as supplied by publisher]
Glial Fibrillary Acidic Protein-Expressing Glia in the Mouse Lung.
ASN Neuro. 2015 Jul;7(5)
Authors: Suarez-Mier GB, Buckwalter MS
Autonomic nerves regulate important functions in visceral organs, including the lung. The postganglionic portion of these nerves is ensheathed by glial cells known as non-myelinating Schwann cells. In the brain, glia play important functional roles in neurotransmission, neuroinflammation, and maintenance of the blood brain barrier. Similarly, enteric glia are now known to have analogous roles in gastrointestinal neurotransmission, inflammatory response, and barrier formation. In contrast to this, very little is known about the function of glia in other visceral organs. Like the gut, the lung forms a barrier between airborne pathogens and the bloodstream, and autonomic lung innervation is known to affect pulmonary inflammation and lung function. Lung glia are described as non-myelinating Schwann cells but their function is not known, and indeed no transgenic tools have been validated to study them in vivo. The primary goal of this research was, therefore, to investigate the relationship between non-myelinating Schwann cells and pulmonary nerves in the airways and vasculature and to validate existing transgenic mouse tools that would be useful for studying their function. We focused on the glial fibrillary acidic protein promoter, which is a cognate marker of astrocytes that is expressed by enteric glia and non-myelinating Schwann cells. We describe the morphology of non-myelinating Schwann cells in the lung and verify that they express glial fibrillary acidic protein and S100, a classic glial marker. Furthermore, we characterize the relationship of non-myelinating Schwann cells to pulmonary nerves. Finally, we report tools for studying their function, including a commercially available transgenic mouse line.
PMID: 26442852 [PubMed - in process]
The History of Patenting Genetic Material.
Annu Rev Genet. 2015 Oct 6;
Authors: Sherkow JS, Greely HT
The US Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics, Inc. declared, for the first time, that isolated human genes cannot be patented. Many have wondered how genes were ever the subjects of patents. The answer lies in a nuanced understanding of both legal and scientific history. Since the early twentieth century, "products of nature" were not eligible to be patented unless they were "isolated and purified" from their surrounding environment. As molecular biology advanced, and the capability to isolate genes both physically and by sequence came to fruition, researchers (and patent offices) began to apply patent-law logic to genes themselves. These patents, along with other biological patents, generated substantial social and political criticism. Myriad Genetics, a company with patents on BRCA1 and BRCA2, two genes critical to assessing early-onset breast and ovarian cancer risk, and with a particularly controversial business approach, became the antagonist in an ultimately successful campaign to overturn gene patents in court. Despite Myriad's defeat, some questions concerning the rights to monopolize genetic information remain. The history leading to that defeat may be relevant to these future issues. Expected final online publication date for the Annual Review of Genetics Volume 49 is November 23, 2015. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
PMID: 26442843 [PubMed - as supplied by publisher]
Microglial Malfunction: The Third Rail in the Development of Alzheimer's Disease.
Trends Neurosci. 2015 Oct;38(10):621-36
Authors: Mhatre SD, Tsai CA, Rubin AJ, James ML, Andreasson KI
Studies of Alzheimer's disease (AD) have predominantly focused on two major pathologies: amyloid-β (Aβ) and hyperphosphorylated tau. These misfolded proteins can accumulate asymptomatically in distinct regions over decades. However, significant Aβ accumulation can be seen in individuals who do not develop dementia, and tau pathology limited to the transentorhinal cortex, which can appear early in adulthood, is usually clinically silent. Thus, an interaction between these pathologies appears to be necessary to initiate and propel disease forward to widespread circuits. Recent multidisciplinary findings strongly suggest that the third factor required for disease progression is an aberrant microglial immune response. This response may initially be beneficial; however, a maladaptive microglial response eventually develops, fueling a feed-forward spread of tau and Aβ pathology.
PMID: 26442696 [PubMed - in process]
Differential Rates of Inadvertent Intravascular Injection during Lumbar Transforaminal Epidural Injections Using Blunt-Tip, Pencil-Point, and Catheter-Extension Needles.
Pain Med. 2015 Oct 7;
Authors: Smuck M, Paulus S, Patel A, Demirjian R, Ith MA, Kennedy DJ
OBJECTIVE: To quantify the incidence of inadvertent vascular penetration during lumbosacral transforaminal epidural injections using blunt-tip, pencil-point, and catheter-extension needles.
STUDY DESIGN/SETTING: This is a prospective, observational, consecutive cohort study.
SUBJECTS: Two hundred consecutive patients undergoing lumbosacral transforaminal epidural injections at an academic outpatient spine center.
METHODS: Four hundred seventy-five fluoroscopically guided lumbosacral transforaminal epidural injections were performed on consecutively consenting patients by one interventional spine physician, using three different needle types. The presence or absence of vascular uptake was determined during contrast injection under live fluoroscopy.
RESULTS: Vascular uptake of contrast was observed in 58 of the total 475 injections, for an overall incidence of 12.2%. By needle type, the incidence of inadvertent vascular uptake was 16.6% (26/157) in the pencil-point group, 15.6% (24/154) in the blunt-tip group, and 4.9% (8/164) in the catheter-extension group. The difference in rates is statistically significant between the catheter-extension needle group and both the pencil-point group (P = 0.0009) and blunt-tip group (P = 0.0024). A secondary analysis was performed to quantify the incidence of functional pitfalls between needle groups, with a significantly lower incidence in the pencil-point group compared to both the catheter-extension (P = 0.0148) and blunt-tip needle (P = 0.0288) groups.
CONCLUSIONS: Blunt-tip and pencil-point needles have comparable risk of inadvertent vascular injection during lumbosacral transforaminal injections. Catheter-extension needles demonstrated a reduce incidence of vascular uptake, but also result in a significantly higher rate of functional pitfalls that limits their usefulness in routine practice.
PMID: 26442619 [PubMed - as supplied by publisher]
Familial risk of non-Hodgkin lymphoma by sex, relationship, age at diagnosis and histology: A joint study from five Nordic countries.
Leukemia. 2015 Oct 7;
Authors: Fallah M, Kharazmi E, Pukkala E, Tretli S, Olsen JH, Tryggvadottir L, Sundquist K, Hemminki K
We aimed to estimate stratified absolute (cumulative) and relative (standardized incidence ratios; SIRs) risks of non-Hodgkin lymphoma (NHL) in relatives of NHL patients. A cohort of 169 830 first-degree relatives of 45 406 NHL patients who were diagnosed between1955 and 2010 in five European countries was followed for cancer incidence. The lifetime (0-79 year) cumulative risk of NHL in siblings of a patient with NHL was 1.6%, which represents a 1.6-fold increased risk (SIR=1.6, 95% CI=1.2-1.9) over the general population risk. NHL risk among parent-offspring pairs was increased up to 1.4-fold (95% CI=1.3-1.5; lifetime risk 1.4%). The lifetime risk was higher when NHL was diagnosed in a sister (2.5% in her brothers and 1.9% in her sisters) or a father (1.7% in his son). When there were >=2 NHL patients diagnosed in a family, the lifetime NHL risk for relatives was 2.1%. Depending on sex and age at diagnosis, twins had a 3.1-12.9% lifetime risk of NHL. Family history of most of histological subtypes of NHL increased the risk of concordant and some discordant subtypes. Familial risk did not significantly change by age at diagnosis of NHL in relatives. Familial risk of NHL was not limited to early onset cases.Leukemia accepted article preview online, 07 October 2015. doi:10.1038/leu.2015.272.
PMID: 26442613 [PubMed - as supplied by publisher]
Metal-to-insulator switching in quantum anomalous Hall states.
Nat Commun. 2015;6:8474
Authors: Kou X, Pan L, Wang J, Fan Y, Choi ES, Lee WL, Nie T, Murata K, Shao Q, Zhang SC, Wang KL
After decades of searching for the dissipationless transport in the absence of any external magnetic field, quantum anomalous Hall effect (QAHE) was recently achieved in magnetic topological insulator films. However, the universal phase diagram of QAHE and its relation with quantum Hall effect (QHE) remain to be investigated. Here, we report the experimental observation of the giant longitudinal resistance peak and zero Hall conductance plateau at the coercive field in the six quintuple-layer (Cr0.12Bi0.26Sb0.62)2Te3 film, and demonstrate the metal-to-insulator switching between two opposite QAHE plateau states up to 0.3 K. Moreover, the universal QAHE phase diagram is confirmed through the angle-dependent measurements. Our results address that the quantum phase transitions in both QAHE and QHE regimes are in the same universality class, yet the microscopic details are different. In addition, the realization of the QAHE insulating state unveils new ways to explore quantum phase-related physics and applications.
PMID: 26442609 [PubMed - in process]
MRI and CT of Low-Grade Fibromyxoid Sarcoma in Children: A Report From Children's Oncology Group Study ARST0332.
AJR Am J Roentgenol. 2015 Aug;205(2):414-20
Authors: Sargar K, Kao SC, Spunt SL, Hawkins DS, Parham DM, Coffin C, McCarville MB
OBJECTIVE: The purpose of this article is to determine the MRI and CT features of low-grade fibromyxoid sarcoma in children.
MATERIALS AND METHODS: We retrospectively analyzed images of 11 pediatric patients with low-grade fibromyxoid sarcoma from a phase 3 clinical trial of nonrhabdomyosarcoma soft-tissue sarcoma (Children's Oncology Group Protocol ARST0332). MRI and CT were performed in 10 and four patients, respectively. Location, size, margin, and composition on imaging were correlated with pathologic findings.
RESULTS: Tumors were located in the extremities in nine patients, and one tumor each was located in the tongue and lung. Tumors were deep in seven patients and superficial in four patients. All tumors were well defined, solitary, and nonmetastatic at presentation. Tumors were complex solid-cystic in eight patients and completely solid in three patients. On T1-weighted images, all tumors had at least some areas hypointense to muscles, and six had a split-fat sign. On STIR or T2-weighted images, eight tumors had areas hypointense to adjacent muscle, and eight tumors had fluid signal intensity. On contrast-enhanced MRI studies, eight tumors had thick enhancing internal septations, and three had peripheral nodular gyriform enhancement. When we correlated imaging to pathologic findings, areas with hypointense signal intensity on both T1- and T2-weighted images were likely related to fibrous component; areas with fluid signal intensity on T2-weighted images were likely related to myxoid component. On CT, all four tumors were hypodense to muscle, and one tumor showed punctate calcific foci.
CONCLUSION: Low-grade fibromyxoid sarcoma is hypodense to muscle on CT. MRI may identify both fibrous and myxoid components of this rare pediatric soft-tissue sarcoma.
PMID: 26204295 [PubMed - indexed for MEDLINE]
Emergency manual implementation: can brief simulation-based or staff trainings increase familiarity and planned clinical use?
Jt Comm J Qual Patient Saf. 2015 May;41(5):212-20
Authors: Goldhaber-Fiebert SN, Lei V, Nandagopal K, Bereknyei S
BACKGROUND: Emergency manuals (EMs)-context-relevant sets of cognitive aids such as crisis checklists-are useful tools to enhance perioperative patient care. Studies in high-hazard industries demonstrate that humans, regardless of expertise, do not optimally retrieve or deploy key knowledge under stress. EM use has been shown in both health care simulation studies and other industries to help expert teams effectively manage critical events. However, clinical adoption and use are still nascent in health care. Recognizing that training with, access to, and cultural acceptance of EMs can be vital elements for successful implementation, this study assessed the impact of a brief in situ operating room (OR) staff training program on familiarity with EMs and intention to use them during critical events.
METHODS: Nine 50-minute training sessions were held with OR staff as part of a broader perioperative EM implementation. Participants primarily included OR nurses and surgical technologists. The simulation-based in situ trainings included why and how to use EMs, familiarization with format, simulated scenarios of critical events, and debriefings. A retrospective pre-post survey was conducted to determine participants' levels of EM familiarity and intentions to use EMs clinically.
RESULTS: The 126 trained OR staff self-reported increases in awareness of the EM (p < .01), familiarity with EM (p < .01), willingness to use for educational review (p < .01), and intention to use during critical events (p < .01). Participants rated the sessions highly and expressed interest in more opportunities to practice using EMs.
CONCLUSIONS: Implementing institutions should not only provide EMs in accessible places in ORs but also incorporate training mechanisms to increase clinicians' familiarity, cultural acceptance, and planned clinical use.
PMID: 25977248 [PubMed - indexed for MEDLINE]
Development and evaluation of an electronic health record-based best-practice discharge checklist for hospital patients.
Jt Comm J Qual Patient Saf. 2015 Mar;41(3):126-31
Authors: Garg T, Lee JY, Evans KH, Chen J, Shieh L
BACKGROUND: Checklists may help reduce discharge errors; however, current paper checklists have limited functionality. In 2013 a best-practice discharge checklist using the electronic health record (EHR) was developed and evaluated at Stanford University Medical Center (Stanford, California) in a cluster randomized trial to evaluate its usage, user satisfaction, and impact on physicians' work flow.
METHODS: The study was divided into four phases.
RESULTS: In Phase I, on the survey (N = 76), most of the participants (54.0%) reported using memory to remember discharge tasks. On a 0-100 scale, perception of checklists as being useful was strong (mean, 66.4; standard deviation [SD], 21.2), as was interest in EHR checklists (64.5, 26.6). In Phase II, the checklist consisted of 15 tasks categorized by admission, hospitalization, and discharge-planning. In Phase III, the checklist was implemented as an EHR "smart-phrase" allowing for automatic insertion. In Phase IV, in a trial with 60 participating physicians, 23 EHR checklist users reported higher usage than 12 paper users (28.5 versus 7.67, p = .019), as well as higher checklist integration with work flow (22.6 versus 1.67, p = .014), usefulness of checklist (33.7 versus. 8.92, p = .041), discharge confidence (30.8 versus 5.00, p = .029), and discharge efficiency (25.5 versus 6.67, p = .056). Increasing EHR checklist use was correlated with usefulness ( r = .85, p < .001), confidence (r = .81, p < .001), and efficiency (r = .87, p < .001).
CONCLUSIONS: The EHR checklist reminded physicians to complete discharge tasks, improved confidence, and increased process efficiency. This is the first study to show that medicine residents use "memory" as the most common method for remembering discharge tasks. These data reinforce the need for a formalized tool, such as a checklist, that residents can rely on to complete important discharge tasks.
PMID: 25977128 [PubMed - indexed for MEDLINE]
The role of the dermatologist in detecting elder abuse and neglect.
J Am Acad Dermatol. 2015 Aug;73(2):285-93
Authors: Danesh MJ, Chang AL
The National Research Council of the National Academies defines elder mistreatment as: (1) intentional actions that cause harm or create serious risk of harm (whether or not harm is intended) to a vulnerable elder by a caregiver or other person who stands in a trust relationship to the elder; or (2) failure by a caregiver to satisfy the elder's basic needs or to protect the elder from harm. Estimates of the prevalence of elder abuse have ranged from 2.2% to 18.4%. Dermatologists are uniquely positioned to identify and manage suspected cases of elder abuse given their expertise in distinguishing skin lesions of abuse from organic medical disease and their patient populations with strong elderly representation. This article discusses aspects of both the screening and management of elder abuse with particular relevance to dermatologists. Like physicians across medical specialties, dermatologists must be familiar with those aspects of elder abuse in screening, diagnosis, management, and reporting that are unique to their field and to those aspects that are applicable to all health care providers.
PMID: 25956658 [PubMed - indexed for MEDLINE]
Creativity is linked to ambition across the bipolar spectrum.
J Affect Disord. 2015 Jun 1;178:160-4
Authors: Johnson SL, Murray G, Hou S, Staudenmaier PJ, Freeman MA, Michalak EE, CREST.BD
OBJECTIVE: Beyond evidence for an association, little is known about the mechanism linking creativity bipolar spectrum conditions. Theory suggests that ambition, which is heightened in bipolar disorder (BD) and associated with creativity in the general population, might be an important variable. The overarching aim of this project was to evaluate whether ambition is related to creativity among those with bipolar spectrum conditions.
METHOD: Across two studies, we examined correlations between a validated self-report measure of ambition, the WASSUP, and creativity. In Study One, 22 individuals diagnosed with BD who self-identified as highly creative completed the WASSUP and a measure of lifetime creative accomplishment. In Study Two, 221 undergraduates completed the WASSUP, a measure of mania risk (the Hypomanic Personality Scale, HPS) and a measure designed to assess creativity in business projects and tasks.
RESULTS: In Study One, WASSUP scores were significantly elevated compared to normative levels in BD, and WASSUP scores were correlated with lifetime creative accomplishment within the artistic sample. In Study Two, mania risk was related to greater ambition and creativity, and ambition was also directly related to greater creativity.
LIMITATIONS: Both studies were limited by the reliance on self-reported ambition.
CONCLUSION: Ambition could be one important component of creative success across the bipolar spectrum.
PMID: 25837549 [PubMed - indexed for MEDLINE]
An exploratory study of responses to low-dose lithium in African Americans and Hispanics.
J Affect Disord. 2015 Jun 1;178:224-8
Authors: Gonzalez Arnold J, Salcedo S, Ketter TA, Calabrese JR, Rabideau DJ, Nierenberg AA, Bazan M, Leon AC, Friedman ES, Iosifescu D, Sylvia LG, Ostacher M, Thase M, Reilly-Harrington NA, Bowden CL
OBJECTIVES: Few prospective studies examine the impact of ethnicity or race on outcomes with lithium for bipolar disorder. This exploratory study examines differences in lithium response and treatment outcomes in Hispanics, African Americans, and non-Hispanic whites with bipolar disorder in the Lithium Treatment Moderate Dose Use Study (LiTMUS).
METHODS: LiTMUS was a six-site randomized controlled trial of low-dose lithium added to optimized treatment (OPT; personalized, evidence-based pharmacotherapy) vs. OPT alone in outpatients with bipolar disorder. Of 283 participants, 47 African Americans, 39 Hispanics, and 175 non-Hispanic whites were examined. We predicted minority groups would have more negative medication attitudes and higher attrition rates, but better clinical outcomes.
RESULTS: African Americans in the lithium group improved more on depression and life functioning compared to whites over the 6 month study. African Americans in the OPT only group had marginal improvement on depression symptoms. For Hispanics, satisfaction with life did not significantly improve in the OPT only group, in contrast to whites and African Americans who improved over time on all measures. Attitudes toward medications did not differ across ethnic/racial groups.
CONCLUSIONS: African Americans show some greater improvements with lithium than non-Hispanic whites, and Hispanics showed more consistent improvements in the lithium group. The impact of low-dose lithium should be studied in a larger sample as there may be particular benefit for African Americans and Hispanics. Given that the control group (regardless of ethnicity/race) had significant improvements, optimized treatment may be beneficial for any ethnic group.
PMID: 25827507 [PubMed - indexed for MEDLINE]
Measuring electric fields and noncovalent interactions using the vibrational stark effect.
Acc Chem Res. 2015 Apr 21;48(4):998-1006
Authors: Fried SD, Boxer SG
Over the past decade, we have developed a spectroscopic approach to measure electric fields inside matter with high spatial (<1 Å) and field (<1 MV/cm) resolution. The approach hinges on exploiting a physical phenomenon known as the vibrational Stark effect (VSE), which ultimately provides a direct mapping between observed vibrational frequencies and electric fields. Therefore, the frequency of a vibrational probe encodes information about the local electric field in the vicinity around the probe. The VSE method has enabled us to understand in great detail the underlying physical nature of several important biomolecular phenomena, such as drug-receptor selectivity in tyrosine kinases, catalysis by the enzyme ketosteroid isomerase, and unidirectional electron transfer in the photosynthetic reaction center. Beyond these specific examples, the VSE has provided a conceptual foundation for how to model intermolecular (noncovalent) interactions in a quantitative, consistent, and general manner. The starting point for research in this area is to choose (or design) a vibrational probe to interrogate the particular system of interest. Vibrational probes are sometimes intrinsic to the system in question, but we have also devised ways to build them into the system (extrinsic probes), often with minimal perturbation. With modern instruments, vibrational frequencies can increasingly be recorded with very high spatial, temporal, and frequency resolution, affording electric field maps correspondingly resolved in space, time, and field magnitude. In this Account, we set out to explain the VSE in broad strokes to make its relevance accessible to chemists of all specialties. Our intention is not to provide an encyclopedic review of published work but rather to motivate the underlying framework of the methodology and to describe how we make and interpret the measurements. Using certain vibrational probes, benchmarked against computer models, it is possible to use the VSE to measure absolute electric fields in arbitrary environments. The VSE approach provides an organizing framework for thinking generally about intermolecular interactions in a quantitative way and may serve as a useful conceptual tool for molecular design.
PMID: 25799082 [PubMed - indexed for MEDLINE]
Active and latent tuberculosis in Brazilian correctional facilities: a cross-sectional study.
BMC Infect Dis. 2015;15:24
Authors: Carbone Ada S, Paião DS, Sgarbi RV, Lemos EF, Cazanti RF, Ota MM, Junior AL, Bampi JV, Elias VP, Simionatto S, Motta-Castro AR, Pompílio MA, de Oliveira SM, Ko AI, Andrews JR, Croda J
BACKGROUND: Tuberculosis (TB) rates among prisoners are more than 20 times that of the general population in Brazil, yet there are limited data available to facilitate the development of effective interventions in this high-transmission setting. We aimed to assess risk factors for TB infection and evaluate the yield of mass screening for active disease among inmates.
METHODS: We administered a questionnaire and tuberculin skin test (TST) to a population-based sample of inmates from 12 prisons in Central-West Brazil and collected sera for HIV testing and two sputum samples for smear microscopy and culture from participants reporting a cough of any duration. Hierarchical Poisson regression models were used to evaluate factors associated with latent tuberculosis infection (LTBI).
RESULTS: We recruited 3,380 inmates, of which 2,861 (84.6%) were males from 8 prisons, and 519 (15.4%) were females from 4 prisons. Among the 1,020 (30%) subjects who reported a cough, we obtained sputum from 691 (68%) and identified 31 cases of active TB for a point prevalence of 917 (95% CI, 623-1302) per 100,000 prisoners. Evaluation of the two sputum smear samples failed to identify 74% of the TB cases, and 29% of the cases reported less than 2 weeks of symptoms. Obtaining a second culture identified an additional 7 (24%) cases. The prevalences of LTBI were 22.5% and 11.7% for male and female prisoners, respectively and duration of incarceration (in years) was associated with LTBI in male and female in the multivariable model (1.04, 95% CI, 1.01-1.07 and 1.34, 95% CI, 1.06-1.70, respectively). The prevalence of LTBI is 8.6% among newly incarcerated inmates, among whom LTBI prevalence significantly increased by 5% with each year of incarceration.
CONCLUSIONS: Although the overall LTBI prevalence among inmates in Central-West Brazil is low, tuberculosis incidence is high (>1,800/100,00), likely due to the high force of infection among a largely susceptible inmate population. Efforts to reduce transmission in prisons may require mass screening for active TB, utilizing sputum culture in case-detection protocols.
PMID: 25608746 [PubMed - indexed for MEDLINE]
Visual manifestations in giant cell arteritis: trend over 5 decades in a population-based cohort.
J Rheumatol. 2015 Feb;42(2):309-15
Authors: Singh AG, Kermani TA, Crowson CS, Weyand CM, Matteson EL, Warrington KJ
OBJECTIVE: To evaluate clinical characteristics, treatment, and outcomes of patients with visual changes from giant cell arteritis (GCA) and to examine trends over the last 5 decades.
METHODS: We reviewed the medical records of a population-based cohort of patients with GCA diagnosed between 1950 and 2004. The clinical, ophthalmological, and laboratory features of patients with visual manifestations attributable to GCA were compared to patients without visual complications. Trends over time were examined using logistic regression modeling adjusted for age and sex.
RESULTS: In a cohort of 204 cases of GCA (mean age 76.0 ± 8.2 yrs, 80% female), visual changes from GCA were observed in 47 patients (23%), and 4.4% suffered complete vision loss. A higher proportion of patients with visual manifestations reported jaw claudication than did patients without visual changes (55% vs 38%, p = 0.04). Over a period of 55 years, we observed a significant decline in the incidence of visual symptoms due to GCA. There was a lower incidence of ischemic optic neuropathy in the 1980-2004 cohort vs 1950-1979 (6% vs 15%, p = 0.03). Patients diagnosed in later decades were more likely to recover from visual symptoms (HR 1.34, 95% CI 1.06-1.71). Chances of recovery were poor in patients with anterior ischemic optic neuropathy or complete vision loss.
CONCLUSION: Incidence of visual symptoms has declined over the past 5 decades, and chances of recovery from visual symptoms have improved. However, complete loss of vision is essentially irreversible. Jaw claudication is associated with higher likelihood of development of visual symptoms.
PMID: 25512481 [PubMed - indexed for MEDLINE]
Assaying the epigenome in limited numbers of cells.
Methods. 2015 Jan 15;72:51-6
Authors: Greenleaf WJ
Spectacular advances in the throughput of DNA sequencing have allowed genome-wide analysis of epigenetic features such as methylation, nucleosome position and post-translational modification, chromatin accessibility and connectivity, and transcription factor binding. However, for rare or precious biological samples, input requirements of many of these methods limit their application. In this review we discuss recent advances for low-input genome-wide analysis of chromatin immunoprecipitation, methylation, DNA accessibility, and chromatin conformation.
PMID: 25461774 [PubMed - indexed for MEDLINE]
Glial cell development and function in zebrafish.
Cold Spring Harb Perspect Biol. 2015 Feb;7(2):a020586
Authors: Lyons DA, Talbot WS
The zebrafish is a premier vertebrate model system that offers many experimental advantages for in vivo imaging and genetic studies. This review provides an overview of glial cell types in the central and peripheral nervous system of zebrafish. We highlight some recent work that exploited the strengths of the zebrafish system to increase the understanding of the role of Gpr126 in Schwann cell myelination and illuminate the mechanisms controlling oligodendrocyte development and myelination. We also summarize similarities and differences between zebrafish radial glia and mammalian astrocytes and consider the possibility that their distinct characteristics may represent extremes in a continuum of cell identity. Finally, we focus on the emergence of zebrafish as a model for elucidating the development and function of microglia. These recent studies have highlighted the power of the zebrafish system for analyzing important aspects of glial development and function.
PMID: 25395296 [PubMed - indexed for MEDLINE]
Studying epithelial morphogenesis in Dictyostelium.
Methods Mol Biol. 2015;1189:267-81
Authors: Dickinson DJ, Nelson WJ, Weis WI
The discovery of polarized epithelial tissue in the social amoeba Dictyostelium discoideum establishes this classical model organism as a novel system for the study of epithelial polarity and morphogenesis. D. discoideum grows as single cells and is easily maintained in cell culture. Starvation of the cells triggers a multicellular developmental process that culminates with the formation of a fruiting body, whose normal morphogenesis is dependent on a polarized epithelium located at the apex of the developing structure. Here, we discuss techniques for genetic manipulation and imaging of multicellular D. discoideum, with a focus on methods that have facilitated the study of the epithelial tissue in this organism.
PMID: 25245700 [PubMed - indexed for MEDLINE]
Prevalence and characterization of pruritus in epidermolysis bullosa.
Pediatr Dermatol. 2015 Jan-Feb;32(1):53-9
Authors: Danial C, Adeduntan R, Gorell ES, Lucky AW, Paller AS, Bruckner A, Pope E, Morel KD, Levy ML, Li S, Gilmore ES, Lane AT
Qualitative data suggest that pruritus is a burdensome symptom in patients with epidermolysis bullosa (EB), but the prevalence of pruritus in children and adults with EB and factors that contribute to pruritus are unknown. The objective of the current study was to quantitatively identify and to characterize pruritus that EB patients experience using a comprehensive online questionnaire. A questionnaire was developed to evaluate pruritus in all ages and all types of EB. Questions that characterize pruritus were included and factors that aggravate symptoms were investigated. Patients from seven North American EB centers were invited to participate. One hundred forty-six of 216 questionnaires were completed (response rate 68%; 73 male, 73 female; median age 20.0 years). Using a 5-point Likert scale (1 = never, 2 = rarely, 3 = sometimes, 4 = often, 5 = always), itchiness was the most bothersome EB complication (mean 3.3). The average daily frequency of pruritus increased with self-reported EB severity. Pruritus was most frequent at bedtime (mean 3.8) and interfered with sleep. Factors that aggravated pruritus included healing wounds, dry skin, infected wounds, stress, heat, dryness, and humidity. Pruritus is common in individuals with EB and can be bothersome. Future studies will need to investigate the most effective treatments given to individuals with EB for pruritus.
PMID: 25236506 [PubMed - indexed for MEDLINE]
Allee effects and species co-existence in an environment where resource abundance varies.
J Theor Biol. 2014 Nov 21;361:61-8
Authors: M'Gonigle LK, Greenspoon PB
Explaining patterns of diversity has long been a central focus in ecology. One of the most challenging problems has been to understand how species occupying similar ecological niches can co-exist because, with limited resources, demographic stochasticity is expected to lead to the eventual extinction of all but one of them. The Allee effect has been widely studied for its impact on the extinction risk of rare species. Its potential role in promoting co-existence has received less attention. Here, we present a model in which two species compete for a single resource across a continuous landscape. We show that Allee effects can promote their co-existence when a simple condition is met: resources are distributed unevenly across space. Furthermore, the Allee effect can stabilize co-existence despite the reduction in population density and consequent increase in demographic stochasticity that it causes. The Allee effect might, therefore, be an important force maintaining diverse communities.
PMID: 25066786 [PubMed - indexed for MEDLINE]
Toxoplasma gondii influences aversive behaviors of female rats in an estrus cycle dependent manner.
Physiol Behav. 2014 Aug;135:98-103
Authors: Golcu D, Gebre RZ, Sapolsky RM
The protozoan Toxoplasma gondii (T. gondii) manipulates the behavior of its rodent intermediate host to facilitate its passage to its feline definitive host. This is accomplished by a reduction of the aversive response that rodents show towards cat odors, which likely increases the predation risk. Females on average show similar changes as males. However, behaviors that relate to aversion and attraction are usually strongly influenced by the estrus cycle. In this study, we replicated behavioral effects of T. gondii in female rats, as well as expanded it to two novel behavioral paradigms. We also characterized the role of the estrus cycle in the behavioral effects of T. gondii on female rats. Uninfected females preferred to spend more time in proximity to rabbit rather than bobcat urine, and in a dark chamber rather than a lit chamber. Infected females lost both of these preferences, and also spent more time investigating social novelty (foreign bedding in their environment). Taken together, these data suggest that infection makes females less risk averse and more exploratory. Furthermore, this effect was influenced by the estrus cycle. Uninfected rats preferred rabbit urine to bobcat urine throughout the cycle except at estrus and metestrus. In contrast, infected rats lost this preference at every stage of the cycle except estrus. Commensurate with the possibility that this was a hormone-dependent effect, infected rats had elevated levels of circulating progesterone, a known anxiolytic.
PMID: 24907696 [PubMed - indexed for MEDLINE]
MIDER: network inference with mutual information distance and entropy reduction.
PLoS One. 2014;9(5):e96732
Authors: Villaverde AF, Ross J, Morán F, Banga JR
The prediction of links among variables from a given dataset is a task referred to as network inference or reverse engineering. It is an open problem in bioinformatics and systems biology, as well as in other areas of science. Information theory, which uses concepts such as mutual information, provides a rigorous framework for addressing it. While a number of information-theoretic methods are already available, most of them focus on a particular type of problem, introducing assumptions that limit their generality. Furthermore, many of these methods lack a publicly available implementation. Here we present MIDER, a method for inferring network structures with information theoretic concepts. It consists of two steps: first, it provides a representation of the network in which the distance among nodes indicates their statistical closeness. Second, it refines the prediction of the existing links to distinguish between direct and indirect interactions and to assign directionality. The method accepts as input time-series data related to some quantitative features of the network nodes (such as e.g. concentrations, if the nodes are chemical species). It takes into account time delays between variables, and allows choosing among several definitions and normalizations of mutual information. It is general purpose: it may be applied to any type of network, cellular or otherwise. A Matlab implementation including source code and data is freely available (http://www.iim.csic.es/~gingproc/mider.html). The performance of MIDER has been evaluated on seven different benchmark problems that cover the main types of cellular networks, including metabolic, gene regulatory, and signaling. Comparisons with state of the art information-theoretic methods have demonstrated the competitive performance of MIDER, as well as its versatility. Its use does not demand any a priori knowledge from the user; the default settings and the adaptive nature of the method provide good results for a wide range of problems without requiring tuning.
PMID: 24806471 [PubMed - indexed for MEDLINE]
JMJD5 regulates cell cycle and pluripotency in human embryonic stem cells.
Stem Cells. 2014 Aug;32(8):2098-110
Authors: Zhu H, Hu S, Baker J
In mammalian embryos, embryonic stem cells (ESCs) and induced pluripotent cells, a shortened G1 phase is correlated with the pluripotent state. To molecularly define this phase, we compared transcripts from the shortened G1 of human ESCs (hESCs) with those from the longer G1 of derived endoderm. We identified JMJD5, a JmjC (Jumonji C) domain containing protein that, when depleted in hESCs, causes the accumulation of cells in G1 phase, loss of pluripotency, and subsequent differentiation into multiple lineages, most prominently ectoderm and trophectoderm. Furthermore, we demonstrate that the JMJD5 phenotype is caused by the upregulation of CDKN1A (p21), as depleting both JMJD5 and CDKN1A (p21) in hESCs restores the rapid G1 phase and rescues the pluripotent state. Overall, we provide genetic and biochemical evidence that the JMJD5/CDKN1A (p21) axis is essential to maintaining the short G1 phase which is critical for pluripotency in hESCs.
PMID: 24740926 [PubMed - indexed for MEDLINE]
Phase 1/2 study of ocaratuzumab, an Fc-engineered humanized anti-CD20 monoclonal antibody, in low-affinity FcγRIIIa patients with previously treated follicular lymphoma.
Leuk Lymphoma. 2015 Jan;56(1):42-8
Authors: Ganjoo KN, de Vos S, Pohlman BL, Flinn IW, Forero-Torres A, Enas NH, Cronier DM, Dang NH, Foon KA, Carpenter SP, Slapak CA, Link BK, Smith MR, Mapara MY, Wooldridge JE
This phase 2 study assessed the safety and efficacy of ocaratuzumab, a humanized anti-CD20 monoclonal antibody. Fifty patients with previously treated follicular lymphoma (FL) and a low-affinity genotype of FcγRIIIa received ocaratuzumab 375 mg/m(2) weekly for 4 weeks. Grade 3/4/5 adverse events (AEs) were reported in 11/1/1 patients, respectively. Serious AEs were reported by 11/50 patients, and three discontinued due to AEs. One patient died from aspiration pneumonia due to possibly drug-related nausea and vomiting. Investigator-assessed response rate was 30% (15/50), including four complete responses (CR), three CR unconfirmed (CRu) and eight partial responses (PR). Investigator-assessed median Progression-free survivial (PFS) was 38.3 weeks. Ocaratuzumab's pharmacokinetic profile was similar to that reported for rituximab. Lymphocyte subset analysis showed significant, selective reduction of B-cells during and after ocaratuzumab treatment. Ocaratuzumab at this dose and schedule is active and well tolerated in patients with previously treated FL with low affinity FcγRIIIa genotypes. ClinTrials registry number: NCT00354926.
PMID: 24717109 [PubMed - indexed for MEDLINE]
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