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  • Article
    Vogt M, Schulz B, Wagdi A, Lebert J, van Belle GJ, Christoph J, Bruegmann T, Patejdl R.
    Theranostics. 2021;11(11):5569-5584.
    Rationale: Antral peristalsis is responsible for gastric emptying. Its failure is called gastroparesis and often caused by dysfunction of enteric neurons and interstitial cells of Cajal (ICC). Current treatment options, including gastric electrical stimulation, are non-satisfying and may improve symptoms but commonly fail to restore gastric emptying. Herein, we explore direct optogenetic stimulation of smooth muscle cells (SMC) via the light-gated non-selective cation channel Channelrhodopsin2 (ChR2) to control gastric motor function. Methods: We used a transgenic mouse model expressing ChR2 in fusion with eYFP under the control of the chicken-β-actin promoter. We performed patch clamp experiments to quantify light-induced currents in isolated SMC, Ca2+ imaging and isometric force measurements of antral smooth muscle strips as well as pressure recordings of intact stomachs to evaluate contractile responses. Light-induced propulsion of gastric contents from the isolated stomach preparation was quantified in video recordings. We furthermore tested optogenetic stimulation in a gastroparesis model induced by neuronal- and ICC-specific damage through methylene blue photo-toxicity. Results: In the stomachs, eYFP signals were restricted to SMC in which blue light (460 nm) induced inward currents typical for ChR2. These depolarizing currents led to contractions in antral smooth muscle strips that were stronger than those triggered by supramaximal electrical field stimulation and comparable to those evoked by global depolarization with high K+ concentration. In the intact stomach, panoramic illumination efficiently increased intragastric pressure achieving 239±46% (n=6) of the pressure induced by electrical field stimulation and triggered gastric transport. Within the gastroparesis model, electric field stimulation completely failed but light still efficiently generated pressure waves. Conclusions: We demonstrate direct optogenetic stimulation of SMC to control gastric contractility. This completely new approach could allow for the restoration of motility in gastroparesis in the future.
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  • Article
    Chung YW, Hwang HY.
    Sensors (Basel). 2010;10(6):5569-89.
    In sensor network, energy conservation is one of the most critical issues since sensor nodes should perform a sensing task for a long time (e.g., lasting a few years) but the battery of them cannot be replaced in most practical situations. For this purpose, numerous energy conservation schemes have been proposed and duty cycling scheme is considered the most suitable power conservation technique, where sensor nodes alternate between states having different levels of power consumption. In order to analyze the energy consumption of energy conservation scheme based on duty cycling, it is essential to obtain the probability of each state. In this paper, we analytically derive steady state probability of sensor node states, i.e., sleep, listen, and active states, based on traffic characteristics and timer values, i.e., sleep timer, listen timer, and active timer. The effect of traffic characteristics and timer values on the steady state probability and energy consumption is analyzed in detail. Our work can provide sensor network operators guideline for selecting appropriate timer values for efficient energy conservation. The analytical methodology developed in this paper can be extended to other energy conservation schemes based on duty cycling with different sensor node states, without much difficulty.
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  • Article
    Leanza L, Zoratti M, Gulbins E, Szabo I.
    Oncogene. 2014 Dec 04;33(49):5569-81.
    Mitochondria, the key bioenergetic intracellular organelles, harbor a number of proteins with proven or hypothetical ion channel functions. Growing evidence points to the important contribution of these channels to the regulation of mitochondrial function, such as ion homeostasis imbalances profoundly affecting energy transducing processes, reactive oxygen species production and mitochondrial integrity. Given the central role of mitochondria in apoptosis, their ion channels with the potential to compromise mitochondrial function have become promising targets for the treatment of malignancies. Importantly, in vivo evidence demonstrates the involvement of the proton-transporting uncoupling protein, a mitochondrial potassium channel, the outer membrane located porin and the permeability transition pore in tumor progression/control. In this review, we focus on mitochondrial channels that have been assigned a definite role in cell death regulation and possess clear oncological relevance. Overall, based on in vivo and in vitro genetic and pharmacological evidence, mitochondrial ion channels are emerging as promising targets for cancer treatment.
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  • Article
    Li Y, Wang H, Zhang H, Liu P, Wang Y, Fang W, Yang H, Li Y, Zhao H.
    Chem Commun (Camb). 2014 May 30;50(42):5569-71.
    Hydrothermally synthesised single crystal NiS nanosheets with an exposed (0001) surface exhibited a light conversion efficiency of 8.62% as an electrocatalyst for dye-sensitised solar cells (DSSCs), significantly higher than that of Pt-based DSSCs (7.36%). The theoretical calculations revealed the exposed (0001) surface with superior catalytic activity owing to the existence of sulfur vacancies.
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  • Article
    Keane KN, Hinchliffe PM, Namdar N, Conceicao JL, Newsholme P, Yovich JL.
    Drug Des Devel Ther. 2015;9:5569-78.
    Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in the circulation and has potent multifunctional activity. Epidemiological evidence suggests that levels of serum DHEA decrease with advancing age, and this has been associated with onset or progression of various age-related ailments, including cognitive decline and dementia, cardiovascular disease, and obesity. Consequently, these findings have sparked intense research interest in DHEA supplementation as an "antiaging" therapy. Currently, DHEA is being used by 25% of in vitro fertilization (IVF) clinicians as an adjuvant in assisted reproductive programs, yet the therapeutic benefit of DHEA is unclear. Here, we examined the use of novel DHEA-containing oral troches in patients undertaking IVF and investigated the impact of these troches on their serum androgen profile. This retrospective study determined the androgen profile of 31 IVF patients before (baseline) and after DHEA supplementation (with DHEA). Baseline serum measurements of testosterone (total and free), DHEA sulfate (DHEAS), sex hormone-binding globulin (SHBG), and androstenedione were made before and after supplementation. Each patient received DHEA troches containing 25 mg of micronized DHEA, and troches were administered sublingually twice daily for a period of no greater than 4 months. Adjuvant treatment with DHEA boosted the serum concentration of a number of androgen-related analytes, including total and free testosterone, androstenedione, and DHEAS, while serum SHBG remained unchanged. Supplementation also significantly increased the free-androgen index in IVF patients. Interestingly, the increase in serum analyte concentration following DHEA supplementation was found to be dependent on body mass index (BMI), but not individual age. Patients with the lowest BMI (<20.0 kg/m(2)) tended to have lower testosterone and DHEAS, but higher SHBG and androstenedione levels in comparison with other BMI groups postsupplementation. However, patients in the highest BMI group (>30.0 kg/m(2)) tended to have lower androgen responses following DHEA supplementation, but these were not statistically different from the corresponding baseline level. This method of DHEA administration results in a similar enhancement of testosterone, DHEAS, and androstenedione levels in comparison with other methods of administration. Furthermore, we showed that BMI significantly influences DHEA uptake and metabolism, and that BMI should be carefully considered during dosage calculation to ensure a significant and robust androgen-profile boost.
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  • Article
    Diamanti-Kandarakis E, Spritzer PM, Sir-Petermann T, Motta AB.
    Curr Pharm Des. 2012;18(34):5569-76.
    The heterogeneity of Polycystic Ovary Syndrome (PCOS) emphasizes the need for a consensual review of the data concerning its diagnosis and treatment and for determination of the relationship between the development of PCOS and the ethnic origin, the social status and the lifespan. Insulin resistance is an important characteristic in women with PCOS that aggravates features of PCOS. This review is focused in the diagnosis and treatment of insulin resistance and the risk factors for PCOS during childhood, adolescence and postmenopause. The role of endocrine disruptors and/or their interaction with PCOS have also been analyzed.
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  • Article
    Allen SA, Carias AM, Anderson MR, Okocha EA, Benning L, McRaven MD, Kelley ZL, Lurain J, Veazey RS, Hope TJ.
    J Virol. 2015 May;89(10):5569-80.
    UNLABELLED: The majority of human immunodeficiency virus type 1 (HIV-1) transmission events occur in women when semen harboring infectious virus is deposited onto the mucosal barriers of the vaginal, ectocervical, and endocervical epithelia. Seminal factors such as semen-derived enhancer of virus infection (SEVI) fibrils were previously shown to greatly enhance the infectivity of HIV-1 in cell culture systems. However, when SEVI is intravaginally applied to living animals, there is no effect on vaginal transmission. To define how SEVI might function in the context of sexual transmission, we applied HIV-1 and SEVI to intact human and rhesus macaque reproductive tract tissues to determine how it influences virus interactions with these barriers. We show that SEVI binds HIV-1 and sequesters most virions to the luminal surface of the stratified squamous epithelium, significantly reducing the number of virions that penetrated the tissue. In the simple columnar epithelium, SEVI was no longer fibrillar in structure and was detached from virions but allowed significantly deeper epithelial virus penetration. These observations reveal that the action of SEVI in intact tissues is very different in the anatomical context of sexual transmission and begin to explain the lack of stimulation of infection observed in the highly relevant mucosal transmission model.
    IMPORTANCE: The most common mode of HIV-1 transmission in women occurs via genital exposure to the semen of HIV-infected men. A productive infection requires the virus to penetrate female reproductive tract epithelial barriers to infect underlying target cells. Certain factors identified within semen, termed semen-derived enhancers of virus infection (SEVI), have been shown to significantly enhance HIV-1 infectivity in cell culture. However, when applied to the genital tracts of living female macaques, SEVI did not enhance virus transmission. Here we show that SEVI functions very differently in the context of intact mucosal tissues. SEVI decreases HIV-1 penetration of squamous epithelial barriers in humans and macaques. At the mucus-coated columnar epithelial barrier, the HIV-1/SEVI interaction is disrupted. These observations suggest that SEVI may not play a significant stimulatory role in the efficiency of male-to-female sexual transmission of HIV.
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  • Article
    Zhang X, Wang JY, Ni J, Zhang LY, Chen ZN.
    Inorg Chem. 2012 May 21;51(10):5569-79.
    Planar platinum(II) complex Pt(Me(3)SiC≡CbpyC≡CSiMe(3))(C≡CC(6)H(4)CF(3)-4)(2) (6) with 5,5'-bis(trimethylsilylethynyl)-2,2'-bipyridine and 4-trifluoromethylphenylacetylide exhibits remarkable luminescence vapochromic and mechanochromic properties and a thermo-triggered luminescence change. Solid-state 6 is selectively sensitive to vapors of oxygen-containing volatile compounds such as tetrahydrofuran (THF), dioxane, and tetrahydropyrane (THP) with phosphorescence vapochromic response red shifts from 561 and 608 nm to 698 nm (THF), 689 nm (dioxane), and 715 nm (THP), respectively. Upon being mechanically ground, desolvated 6, 6·CH(2)Cl(2), and 6·(1)/(2)CH(2)ClCH(2)Cl exhibit significant mechanoluminescence red shifts from 561 and 608 nm to 730 nm, while vapochromic crystalline species 6·THF, 6·dioxane, or 6·THP affords a mechanoluminescence blue shift from 698 nm (THF), 689 nm (dioxane), or 715 nm (THP) to 645 nm, respectively. When the compounds are heated, a thermo-triggered luminescence change occurs, in which bright yellow luminescence at 561 and 608 nm turns to red luminescence at 667 nm with a drastic red shift. The multi-stimulus-responsive luminescence switches have been monitored by the changes in emission spectra and X-ray diffraction patterns. Both X-ray crystallographic and density functional theory studies suggest that the variation in the intermolecular Pt-Pt interaction is the key factor in inducing an intriguing luminescence switch.
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  • Article
    Green D, Eyre H, Singh A, Taylor JT, Chu J, Jeys L, Sumathi V, Coonar A, Rassl D, Babur M, Forster D, Alzabin S, Ponthan F, McMahon A, Bigger B, Reekie T, Kassiou M, Williams K, Dalmay T, Fraser WD, Finegan KG.
    Oncogene. 2020 08;39(33):5553-5569.
    Metastasis is the leading cause of cancer-related death. This multistage process involves contribution from both tumour cells and the tumour stroma to release metastatic cells into the circulation. Circulating tumour cells (CTCs) survive circulatory cytotoxicity, extravasate and colonise secondary sites effecting metastatic outcome. Reprogramming the transcriptomic landscape is a metastatic hallmark, but detecting underlying master regulators that drive pathological gene expression is a key challenge, especially in childhood cancer. Here we used whole tumour plus single-cell RNA-sequencing in primary bone cancer and CTCs to perform weighted gene co-expression network analysis to systematically detect coordinated changes in metastatic transcript expression. This approach with comparisons applied to data collected from cell line models, clinical samples and xenograft mouse models revealed mitogen-activated protein kinase 7/matrix metallopeptidase 9 (MAPK7/MMP9) signalling as a driver for primary bone cancer metastasis. RNA interference knockdown of MAPK7 reduces proliferation, colony formation, migration, tumour growth, macrophage residency/polarisation and lung metastasis. Parallel to these observations were reduction of activated interleukins IL1B, IL6, IL8 plus mesenchymal markers VIM and VEGF in response to MAPK7 loss. Our results implicate a newly discovered, multidimensional MAPK7/MMP9 signalling hub in primary bone cancer metastasis that is clinically actionable.
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  • Article
    Wesener T.
    PeerJ. 2018;6:e5569.
    The pill millipede species Glomeris aurita Koch, 1847 remained of relative unknown origin and appearance until its recent rediscovery in samples from the Bergamasque Alps, northern Italy. In order to provide an integrative redescription and accurate identification of the high-altitude microendemic G. aurita, COI barcode sequences from three individuals coming from two different localities were obtained. These sequences are compared with those of the syntopic endemic G. oblongoguttata Verhoeff, 1894, the widespread black morph of G. romana Verhoeff, 1900, as well as several widespread species including G. marginata Villers, 1789, G. connexa Koch, 1847, and G. klugii Brandt, 1833, which have rare colour morphs that exhibit some similarity to G. aurita. To rule-out any identity confusion of G. aurita with other high-altitude or little-known Italian Glomeris, specimens of G. transalpina Koch, 1836, G. oropensis Verhoeff, 1934, and G. primordialis Verhoeff, 1932 were also added to the dataset. Altogether, 24 sequences were compared. Morphologically, the specimens of G. aurita were studied utilizing scanning electron microscopy as well as non-invasive micro-CT technology. The distribution of both Bergamasque endemics, G. aurita and G. oblongoguttata, could be mapped and compared utilizing samples from the Museo civico di Scienze Naturali di Bergamo, as well as photographic evidence from an Italian naturalist forum. G. aurita has a very short active period and is the first known pill millipede species restricted to mountain tops and cold places, possibly representing a Nunatak survivor.
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  • Article
    Duan P, Zhu X, Liu M.
    Chem Commun (Camb). 2011 May 21;47(19):5569-71.
    Three isomeric pyridine-containing L-glutamic lipids formed organogels in DMSO and self-assembled into different nanostructures of nanofiber, nanotwist and nanotube depending on the substituent position in the pyridine ring.
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  • Article
    Bankar SK, Mathew J, Ramasastry SS.
    Chem Commun (Camb). 2016 Apr 25;52(32):5569-72.
    An unusual and facile approach for the synthesis of 2-benzofuranyl-3-hydroxyacetones from 6-acetoxy-β-pyrones and phenols is presented. The synthetic sequence involves a cascade transacetalisation, Fries-type O → C rearrangement followed by Michael addition and ring-opening aromatisation. The versatility of this method was further demonstrated via the synthesis of 4,4a-dihydropyrano[3,2-b]benzofuran-3-ones, furo[3,2-c]coumarins, and spiro[benzofuran-2,2'-furan]-4'-ones. The unexpected cascade event would also provide new possible considerations in the β-pyrone-involved organic synthesis.
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  • Article
    Dolka I, Czopowicz M, Stopka D, Wojtkowska A, Kaszak I, Sapierzyński R.
    Sci Rep. 2024 03 06;14(1):5569.
    This is a comprehensive retrospective study to characterize female dogs with canine mammary tumors (CMTs) using a dataset retrieved from the archives of the Division of Animal Pathology, Institute of Veterinary Medicine in Warsaw, and to identify prognostic factors. Clinical and histopathological data of 1447 dogs with CMTs were included. Malignant tumours were found in 83.3% (n = 1206), benign tumours in 11.7% (n = 169), and non-neoplastic lesions in 5.0% (n = 72) of dogs. Dogs most often had grade II carcinomas (38.2%, 215/562) of a single histological subtype (88.5%, 1281/1447), mostly simple carcinoma (35.3%, 510/1447). Dogs with a median age of 10 years significantly often had larger (≥ 3 cm) and malignant CMTs, whereas intact females had smaller tumours (median size 2.0 cm). However, the threshold value for the age of the dog in the differentiation of malignant and non-neoplastic/benign masses could not be determined. Most females were hormonally active (76.4%, 372/487). Hormonally active dogs significantly more often had multiple tumours. Multiple tumours were significantly smaller (median 2.5 cm) than single ones. Among pedigree dogs, small-breed dogs were mostly recorded (43%, 428/1006). Twelve breeds had an increased risk of CMTs, regardless of tumour behaviour, compared with the theoretical distribution of pedigree dogs in Poland. Four breeds were often affected only by malignant and other four breeds only by non-neoplastic/benign CMT. Large-breed dogs were significantly younger and affected by larger CMT (median 4 cm) compared with small- and medium-breed dogs. Ninety dogs with a malignant CMT and complete records were included in the full analysis of CMT-specific survival (CMT-SS) with a median follow-up time of 20.0 months. We showed that the timing of ovariohysterectomy in relation to mastectomy was significantly associated with grade, CMT-SS, and CMT-related death. We indicated the low diagnostic accuracy of palpation of regional lymph nodes (RLN) in the prediction of their metastatic involvement. By multivariable analysis, dogs with neoplastic emboli, tumour ulceration, and simple or complex carcinoma had a significantly higher risk of local recurrence. Tumour size > 3 cm was as a strong independent predictor of lung metastases. Compared with dogs with an easily separated localized tumour, dogs with a multiple/diffuse malignant CMT pattern had a fivefold higher risk of death. The risk of death was significantly higher in the presence of neoplastic emboli (~ fivefold) and tumour ulceration (~ fourfold). Furthermore, the presence of neoplastic emboli and large tumour size were independent predictors of CMT-related death.
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  • Article
    Miwa S, Takeuchi A, Shirai T, Yamamoto N, Hayashi K, Nishida H, Kimura H, Igarashi K, Tsuchiya H.
    Anticancer Res. 2014 Oct;34(10):5569-77.
    BACKGROUND: Tumor-bearing frozen autografts have been used for reconstruction of bone defects after resection of bone tumors. In the present study, outcomes and complications of reconstruction using frozen autografts were assessed to determine indications for this procedure in patients with metastatic bone lesions.
    PATIENTS AND METHODS: Twenty-two patients were treated with reconstruction using frozen autografts. The surgical technique involved excision of the bone lesion, curettage, freezing in liquid nitrogen, thawing and reconstruction.
    RESULTS: Limb function was evaluated in 11 patients; wa found excellent in 10 patients and good in 1 patient. Five-year overall survival and disease-free survival rates were 46.7% and 26.3%, respectively. Five-year fracture-free survival and recurrence-free survival rates were 79.9% and 100%, respectively. Complications were observed in 6 patients and included fractures (4), deep infection (1) and osteoarthritis (1).
    CONCLUSION: Reconstruction using frozen autografts is a beneficial treatment option in patients with long expected survival or complete cure of the primary cancer.
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  • Article
    Lee S, Axelsen TV, Jessen N, Pedersen SF, Vahl P, Boedtkjer E.
    Oncogene. 2018 10;37(41):5569-5584.
    Metabolic acid production challenges cellular pH homeostasis in solid cancer tissue, and mechanisms of net acid extrusion represent promising new targets for breast cancer therapy. Here, we used genetically engineered mice to investigate the contribution of the Na+,HCO3--cotransporter NBCn1 (Slc4a7) to intracellular acid-base regulation in ErbB2-induced breast cancer tissue and the consequences of NBCn1 knockout for breast tumor development and growth. We demonstrate an approximately 2-fold increase of NBCn1 protein abundance in ErbB2-induced breast cancer tissue compared to normal breast tissue despite a 4-fold decrease in the NBCn1 mRNA level. In congruence, we show that NBCn1 facilitates net acid extrusion and elevates steady-state intracellular pH in breast cancer tissue. Disruption of NBCn1 expression delayed ErbB2-induced breast carcinogenesis from a median tumor-free survival of 9.5 months in wild-type mice to 12 months in NBCn1-knockout mice and decelerated the tumor growth rate by approximately 1/3. Glycolytic metabolism-evaluated based on the interstitial concentrations of lactate and glucose measured in microdialysates-was increased in breast cancer tissue compared to normal breast tissue, but was unaffected by NBCn1 knockout. Disruption of NBCn1 expression inhibited cell proliferation-evaluated by staining for the proliferative marker Ki67-particularly in central tumor areas with predicted increase in acid loading from glycolytic metabolism. In conclusion, NBCn1 regulates intracellular pH in ErbB2-induced breast cancer tissue by providing a pathway for cellular uptake of HCO3-, which can neutralize metabolic acidic waste products. Disrupting NBCn1 expression delays ErbB2-induced breast cancer development, inhibits cancer cell proliferation, and decelerates tumor growth.
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  • Article
    Sánchez-Rodríguez J, Raufaste C, Argentina M.
    Nat Commun. 2023 09 09;14(1):5569.
    Undulatory swimming is the predominant form of locomotion in aquatic vertebrates. A myriad of animals of different species and sizes oscillate their bodies to propel themselves in aquatic environments with swimming speed scaling as the product of the animal length by the oscillation frequency. Although frequency tuning is the primary means by which a swimmer selects its speed, there is no consensus on the mechanisms involved. In this article, we propose scaling laws for undulatory swimmers that relate oscillation frequency to length by taking into account both the biological characteristics of the muscles and the interaction of the moving swimmer with its environment. Results are supported by an extensive literature review including approximately 1200 individuals of different species, sizes and swimming environments. We highlight a crossover in size around 0.5-1 m. Below this value, the frequency can be tuned between 2-20 Hz due to biological constraints and the interplay between slow and fast muscles. Above this value, the fluid-swimmer interaction must be taken into account and the frequency is inversely proportional to the length of the animal. This approach predicts a maximum swimming speed around 5-10 m.s-1 for large swimmers, consistent with the threshold to prevent bubble cavitation.
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  • Article
    Leigh J, Qureshi D, Sucha E, Mahdavi R, Kushnir I, Lavallée LT, Bosse D, Webber C, Tanuseputro P, Ong M.
    Cancer Med. 2023 03;12(5):5569-5579.
    INTRODUCTION: Life-prolonging therapies (LPTs) are rapidly evolving for the treatment of advanced prostate cancer, although factors associated with real-world uptake are not well characterized.
    METHODS: In this cohort of prostate-cancer decedents, we analyzed factors associated with LPT access. Population-level databases from Ontario, Canada identified patients 65 years or older with prostate cancer receiving androgen deprivation therapy and who died of prostate cancer between 2013 and 2017. Univariate and multivariable analyses assessed the association between baseline characteristics and receipt of LPT in the 2 years prior to death.
    RESULTS: Of 3575 patients who died of prostate cancer, 40.4% (n = 1443) received LPT, which comprised abiraterone (66.3%), docetaxel (50.3%), enzalutamide (17.2%), radium-223 (10.0%), and/or cabazitaxel (3.5%). Use of LPT increased by year of death (2013: 22.7%, 2014: 31.8%, 2015: 41.8%, 2016: 49.1%, and 2017: 57.9%, p < 0.0001), driven by uptake of all agents except docetaxel. Adjusted odds of use were higher for patients seen at Regional Cancer Centers (OR: 1.8, 95% CI: 1.5-2.1) and who received prior prostate-directed therapy (OR: 1.3, 95% CI: 1.0-1.5), but lower with advanced age (≥85: OR: 0.54, 95% CI:0.39-0.75), increased chronic conditions (≥6: OR: 0.62, 95% CI: 0.43-0.92), and long-term care residency (OR: 0.38, 95% CI: 0.17-0.89). Income, stage at presentation, and distance to the cancer center were not associated with LPT uptake.
    CONCLUSION: In this cohort of prostate cancer-decedents, real-world uptake of novel prostate cancer therapies occurred at substantially higher rates for patients receiving care at Regional Cancer Centers, reinforcing the potential benefits for treatment access for patients referred to specialist centers.
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  • Article
    Portmann R, Beyerle U, Davin E, Fischer EM, De Hertog S, Schemm S.
    Nat Commun. 2022 10 04;13(1):5569.
    Forests can store large amounts of carbon and provide essential ecosystem services. Massive tree planting is thus sometimes portrayed as a panacea to mitigate climate change and related impacts. Recent controversies about the potential benefits and drawbacks of forestation have centered on the carbon storage potential of forests and the local or global thermodynamic impacts. Here we discuss how global-scale forestation and deforestation change the Earth's energy balance, thereby affect the global atmospheric circulation and even have profound effects on the ocean circulation. We perform multicentury coupled climate model simulations in which preindustrial vegetation cover is either completely forested or deforested and carbon dioxide mixing ratio is kept constant. We show that global-scale forestation leads to a weakening and poleward shift of the Northern mid-latitude circulation, slows-down the Atlantic meridional overturning circulation, and affects the strength of the Hadley cell, whereas deforestation leads to reversed changes. Consequently, both land surface changes substantially affect regional precipitation, temperature, clouds, and surface wind patterns across the globe. The design process of large-scale forestation projects thus needs to take into account global circulation adjustments and their influence on remote climate.
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  • Article
    Fischer MM, Herzel H, Blüthgen N.
    Sci Rep. 2022 04 02;12(1):5569.
    The intestinal epithelium is one of the fastest renewing tissues in mammals. It shows a hierarchical organisation, where intestinal stem cells at the base of crypts give rise to rapidly dividing transit amplifying cells that in turn renew the pool of short-lived differentiated cells. Upon injury and stem-cell loss, cells can also de-differentiate. Tissue homeostasis requires a tightly regulated balance of differentiation and stem cell proliferation, and failure can lead to tissue extinction or to unbounded growth and cancerous lesions. Here, we present a two-compartment mathematical model of intestinal epithelium population dynamics that includes a known feedback inhibition of stem cell differentiation by differentiated cells. The model shows that feedback regulation stabilises the number of differentiated cells as these become invariant to changes in their apoptosis rate. Stability of the system is largely independent of feedback strength and shape, but specific thresholds exist which if bypassed cause unbounded growth. When dedifferentiation is added to the model, we find that the system can recover faster after certain external perturbations. However, dedifferentiation makes the system more prone to losing homeostasis. Taken together, our mathematical model shows how a feedback-controlled hierarchical tissue can maintain homeostasis and can be robust to many external perturbations.
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  • Article
    Dey NEY, Amponsah B.
    Heliyon. 2020 Nov;6(11):e05569.
    BACKGROUND: While parenting a child with special needs is burdensome, some parents do overcome through protective resources. Social support has been widely linked to this unique ability to overcome the challenges of raising a child with special needs. In spite of this, there is still paucity of research about the influence of the sources of perceived social support on this ability, known as resilience.
    AIM: This study examined three sources of perceived social support-family, friends and significant other-on the resilience of Ghanaian parents raising children with special needs while adjusting for covariates (parental gender, marital status and educational level).
    METHODS: One hundred and seven (107) biological parents were recruited from special schools and parents support groups in Accra, Ghana. They completed paper-and-pencil or online questionnaires on resilience and perceived social support.
    RESULTS: Output from hierarchical multiple regression after adjusting for covariates showed that only support from significant others predicted resilience. Additionally, being married was positively and holding a higher education was inversely associated with resilience.
    CONCLUSION AND IMPLICATION: These findings indicate the importance of support from significant others in the resiliency of parents but underscore the need to fully integrate and emphasize support from the other sources in resilience enhancing interventions.
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