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- ArticleZheng Q.MethodsX. 2023;10:101997.Urban flooding disasters caused by frequent heavy rainfall threaten the safety of residents and socioeconomic development. Thus, risk evaluation of urban inundation is a vital component of sustainable urban development. Analytical hierarchical process (AHP) and decision-making trial and evaluation laboratory (DEMATEL) are common methods applied to flood risk evaluation. The former focuses on the relationship among different layers, while the latter reflects the relationship of factors in one layer. Moreover, the ambiguity in the decision-making process can be reduced by the uncertainty system. Therefore, the proposed method integrates grey theory and utilises the characteristics of DEMATEL to establish the AHP comparison matrix, particularly when the scores given by experts' questionnaires are scattered. The method was applied to the risk assessment of urban inundation in Zhengzhou and verified by its flooding disaster sites that occurred during the 20 July storm in 2021 [1].•Developed approach merges grey theory, DEMATEL, and AHP methods;•Application of G-DEMATEL-AHP method in risk assessment of urban inundation;•The proposed method can increase the reliability of risk assessment results.
- ArticlePane M, Berti B, Capasso A, Coratti G, Varone A, D'Amico A, Messina S, Masson R, Sansone VA, ... Show More Donati MA, Agosto C, Bruno C, Ricci F, Pini A, Gagliardi D, Filosto M, Corti S, Leone D, Palermo C, Onesimo R, De Sanctis R, Ricci M, Bitetti I, Sframeli M, Dosi C, Albamonte E, Ticci C, Brolatti N, Bertini E, Finkel R, Mercuri E, ITASMAc group.EClinicalMedicine. 2023 May;59:101997.Background: Efficacy and safety of onasemnogene abeparvovec (OA) for Spinal Muscular Atrophy infants under 7 months and <8.5 kg has been reported in clinical trials. This study examines efficacy and safety predictors in a wide age (22 days-72 months) and weight (3.2-17 kg) range, also including patients previously treated with other drugs.
Methods: 46 patients were treated for 12 months between January 2020 and March 2022. Safety profile was also available for another 21 patients with at least 6 month follow-up after OA infusion. 19/67 were treatment naïve when treated with OA. Motor function was measured with the CHOP-INTEND.
Findings: CHOP-INTEND changes varied among age groups. Baseline score and age at OA treatment best predicted changes. A mixed model post-hoc analysis showed that in patients treated before the age of 24 months the CHOP-INTEND changes were already significant 3 months after OA while in those treated after the age of 24 months the difference was only significant 12 months after OA. Adverse events occurred in 51/67. The risk for elevated transaminases serum levels was higher in older patients. This was also true for weight and for pre-treatment with nusinersen when analysed individually. A binomial negative regression analysis showed that only age at OA treatment had a significant effect on the risk of elevated transaminases.
Interpretation: Our paper describes OA 12-month follow-up showing efficacy across various age and weight groups not targeted by clinical trials. The study identifies prognostic factors for safety and efficacy in treatment selection.
Funding: None. - ArticleFu CHY, Fan Y, Davatzikos C.Neuroimage Clin. 2019;24:101997.It has been 10 years since machine learning was first applied to neuroimaging data in psychiatric disorders to identify diagnostic and prognostic markers at the level of the individual. Proof of concept findings in major depression have since been extended in international samples and are beginning to include hundreds of samples from multisite data. Neuroimaging provides the unique capability to detect an acute depressive state in major depression, while we would not expect perfect classification with current diagnostic criteria which are based solely on clinical features. We review developments and the potential impact of heterogeneity, as well as homogeneity, on classification for diagnosis and prediction of clinical outcome. It is likely that there are distinct biotypes which comprise the disorder and which predict clinical outcome. Neuroimaging-based biotypes could aid in identifying the illness in individuals who are unable to recognise their illness and perhaps to identify the treatment resistant form early in the course of the illness. We propose that heterogeneous symptom profiles can arise from a limited number of neural biotypes and that apparently heterogeneous clinical outcomes include a common baseline predictor and common mechanism of treatment. Baseline predictors of clinical outcome reflect factors which indicate the general likelihood of response as well as those which are selective for a particular form of treatment. Irrespective of the mechanism, the capacity for response will moderate the outcome, which includes inherent models of interpersonal relationships that could be associated with genetic risk load and represented by patterns of functional and structural neural correlates as a predictive biomarker. We propose that methods which directly address heterogeneity are essential and that a synergistic combination could bring together data-driven inductive and symptom-based deductive approaches. Through this iterative process, major depression can develop from being syndrome characterized by a collection of symptoms to a disease with an identifiable pathophysiology.
- ArticleSemeere A, Byakwaga H, Laker-Oketta M, Freeman E, Busakhala N, Wenger M, Kasozi C, Ssemakadde M, Bwana M, Kanyesigye M, Kadama-Makanga P, Rotich E, Kisuya J, Sang E, Maurer T, Wools-Kaloustian K, Kambugu A, Martin J.Cancer Epidemiol. 2021 10;74:101997.BACKGROUND: Rapid case ascertainment (RCA) refers to the expeditious and detailed examination of patients with a potentially rapidly fatal disease shortly after diagnosis. RCA is frequently performed in resource-rich settings to facilitate cancer research. Despite its utility, RCA is rarely implemented in resource-limited settings and has not been performed for malignancies. One cancer and context that would benefit from RCA in a resource-limited setting is HIV-related Kaposi sarcoma (KS) in sub-Saharan Africa.
METHODS: To determine the feasibility of RCA for KS, we searched for all potential newly diagnosed KS among HIV-infected adults attending three community-based facilities in Uganda and Kenya. Searching involved querying of electronic medical records, pathology record review, and notification by clinicians. Upon identification, a team verified eligibility and attempted to locate patients to perform RCA, which included epidemiologic, clinical and laboratory measurements.
RESULTS: We identified 593 patients with suspected new KS. Of the 593, 171 were ineligible, mainly because biopsy failed to confirm KS (65%) or KS was not new (30%). Among the 422 remaining, RCA was performed within 1 month for 56% of patients and within 3 months for 65% (95% confidence interval: 59 to 70%). Reasons for not performing RCA included intervening death (47%), inability to contact (44%), refusal/unsuitable to consent (8.3%), and patient re-location (0.7%).
CONCLUSIONS: We found that RCA - an important tool for cancer research in resource-rich settings - is feasible for the investigation of community-representative KS in East Africa. Feasibility of RCA for KS suggests feasibility for other cancers in Africa. - ArticleMüller N, Khobta A.Redox Biol. 2021 07;43:101997.The oxidation-induced DNA modification 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) was recently implicated in the activation and repression of gene transcription. We aimed at a systematic characterisation of the impacts of 8-oxodG on the activity of a GC box placed upstream from the RNA polymerase II core promoter. With the help of reporters carrying single synthetic 8-oxodG residues at four conserved G:C base pairs (underlined) within the 5'-TGGGCGGAGC-3' GC box sequence, we identified two modes of interference of 8-oxodG with the promoter activity. Firstly, 8-oxodG in the purine-rich (but not in the pyrimidine-rich) strand caused direct impairment of transcriptional activation. In addition, and independently of the first mechanism, 8-oxodG initiated a decline of the gene expression, which was mediated by the specific DNA glycosylase OGG1. For the different 8-oxodG positions, the magnitude of this effect reflected the excision preferences of OGG1. Thus, 8-oxodG seeded in the pyrimidine-rich strand was excised with the highest efficiency and caused the most pronounced decrease of the promoter activity. Conversely, 8-oxodG in the symmetric position within the same CpG dinucleotide, was poorly excised and induced no decline of the gene expression. Of note, abasic lesions caused gene silencing in both positions. By contrast, an uncleavable apurinic lesion in the pyrimidine-rich strand enhanced the GC box activity, suggesting that the AP endonuclease step provides a switch between the active versus repressed promoter states during base excision repair.
- ArticleParr AC, Calabro F, Larsen B, Tervo-Clemmens B, Elliot S, Foran W, Olafsson V, Luna B.Prog Neurobiol. 2021 06;201:101997.Characterizing developmental changes in frontostriatal circuitry is critical to understanding adolescent development and can clarify neurobiological mechanisms underlying increased reward sensitivity and risk-taking and the emergence of psychopathology during this period. However, the role of striatal neurobiology in the development of frontostriatal circuitry through human adolescence remains largely unknown. We examined background connectivity during a reward-guided decision-making task ("reward-state"), in addition to resting-state, and assessed the association between age-related changes in frontostriatal connectivity and age-related changes in reward learning and risk-taking through adolescence. Further, we examined the contribution of dopaminergic processes to changes in frontostriatal circuitry and decision-making using MR-based assessments of striatal tissue-iron as a correlate of dopamine-related neurobiology. Connectivity between the nucleus accumbens (NAcc) and ventral anterior cingulate, subgenual cingulate, and orbitofrontal cortices decreased through adolescence into adulthood, and decreases in reward-state connectivity were associated with improvements reward-guided decision-making as well as with decreases in risk-taking. Finally, NAcc tissue-iron mediated age-related changes and was associated with variability in connectivity, and developmental increases in NAcc R2' corresponded with developmental decreases in connectivity. Our results provide evidence that dopamine-related striatal properties contribute to the specialization of frontostriatal circuitry, potentially underlying changes in risk-taking and reward sensitivity into adulthood.
- ArticleLong M, Peltekis A, González-Fernández C, Hégaret H, Bailleul B.Harmful Algae. 2021 03;103:101997.Allelopathy is an efficient strategy by which some microalgae can outcompete other species. Allelochemicals from the toxic dinoflagellate Alexandrium minutum have deleterious effects on diatoms, inhibiting metabolism and photosynthesis and therefore give a competitive advantage to the dinoflagellate. The precise mechanisms of allelochemical interactions and the molecular target of allelochemicals remain however unknown. To understand the mechanisms, the short-term effects of A. minutum allelochemicals on the physiology of the diatom Chaetoceros muelleri were investigated. The effects of a culture filtrate were measured on the diatom cytoplasmic membrane integrity (polarity and permeability) using flow-cytometry and on the photosynthetic performance using fluorescence and absorption spectroscopy. Within 10 min, the unknown allelochemicals induced a depolarization of the cytoplasmic membranes and an impairment of photosynthesis through the inhibition of the plastoquinone-mediated electron transfer between photosystem II and cytochrome b6f. At longer time of exposure, the cytoplasmic membranes were permeable and the integrity of photosystems I, II and cytochrome b6f was compromised. Our demonstration of the essential role of membranes in this allelochemical interaction provides new insights for the elucidation of the nature of the allelochemicals. The relationship between cytoplasmic membranes and the inhibition of the photosynthetic electron transfer remains however unclear and warrants further investigation.
- ArticleRusso C, Patanè M, Vicario N, Di Bella V, Cosentini I, Barresi V, Gulino R, Pellitteri R, Russo A, Stanzani S.Neuropeptides. 2020 Feb;79:101997.Olfactory Ensheathing Cells (OECs) are glial cells able to secrete different neurotrophic growth factors and thus promote axonal growth, also acting as a mechanical support. In the olfactory system, during development, they drive the non-myelinated axons of the Olfactory Receptor Neurons (ORNs) towards the Olfactory Bulb (OB). Ghrelin (Ghre), a gut-brain peptide hormone, and its receptor (GHS-R 1a) are expressed in different parts of the central nervous system. In the last few years, this peptide has stimulated particular interest as results show it to be a neuroprotective factor with antioxidant, anti-inflammatory and anti-apoptotic properties. Our previous studies showed that OB mitral cells express Ghre, thus being able to play an important role in regulating food behavior in response to odors. In this study, we investigated the presence of Ghre and GHS-R 1a in primary mouse OECs. The expression of both Ghre and its receptor was assessed by an immunocytochemical technique, Western Blot and Polymerase Chain Reaction (PCR) analysis. Our results demonstrated that OECs are able to express both Ghre and GHS-R 1a and that these proteins are detectable after extensive passages in vitro; in addition, PCR analysis further confirmed these data. Therefore, we can hypothesize that Ghre and GHS-R 1a interact with a reinforcement function, in the peripheral olfactory circuit, providing a neurotrophic support to the synaptic interaction between ORNs and mitral cells.
- ArticlePickett L, Liddy R, Davis N, Foran P, Singh J, Quinlan M.Urol Case Rep. 2022 May;42:101997.Testicular germ cell regression is a rare, generally metastatic phenomenon which describes the spontaneous, complete, or partial regression of a testicular germ cell tumour. As a result, studies have focused on defining specific histopathological criteria to establish if the resected testis is the primary source of the germ cell tumour. There are few publications which describe its presentation in the absence of distant metastases with elevated tumour markers and suspicious findings on testicular ultrasound. We present the clinical presentation and radiological features of a non-metastatic regressed testicular germ cell tumour following scrotal trauma in a post pubertal male.
- ArticleTripathi M, Gauthier K, Sandireddy R, Zhou J, Guptta P, Sakthivel S, Teo WW, Naing YT, Arul K, Tikno K, Park SH, Wu Y, Wang L, Bay BH, Sun L, Giguere V, Chow PKH, Ghosh S, McDonnell DP, Yen PM, Singh BK.Mol Metab. 2024 Sep;87:101997.OBJECTIVE: Currently, little is known about the mechanism(s) regulating global and specific protein translation during metabolic dysfunction-associated steatohepatitis (MASH; previously known as non-alcoholic steatohepatitis, NASH).
METHODS: Unbiased label-free quantitative proteome, puromycin-labelling and polysome profiling were used to understand protein translation activity in vitro and in vivo.
RESULTS: We observed a global decrease in protein translation during lipotoxicity in human primary hepatocytes, mouse hepatic AML12 cells, and livers from a dietary mouse model of MASH. Interestingly, proteomic analysis showed that Rplp1, which regulates ribosome and translation pathways, was one of the most downregulated proteins. Moreover, decreased Esrra expression and binding to the Rplp1 promoter, diminished Rplp1 gene expression during lipotoxicity. This, in turn, reduced global protein translation and Esrra/Rplp1-dependent translation of lysosome (Lamp2, Ctsd) and autophagy (sqstm1, Map1lc3b) proteins. Of note, Esrra did not increase its binding to these gene promoters or their gene transcription, confirming its regulation of their translation during lipotoxicity. Notably, hepatic Esrra-Rplp1-dependent translation of lysosomal and autophagy proteins also was impaired in MASH patients and liver-specific Esrra knockout mice. Remarkably, alternate day fasting induced Esrra-Rplp1-dependent expression of lysosomal proteins, restored autophagy, and reduced lipotoxicity, inflammation, and fibrosis in hepatic cell culture and in vivo models of MASH.
CONCLUSIONS: Esrra regulation of Rplp1-mediated translation of lysosome/autolysosome proteins was downregulated during MASH. Alternate day fasting activated this novel pathway and improved MASH, suggesting that Esrra and Rplp1 may serve as therapeutic targets for MASH. Our findings also provided the first example of a nuclear hormone receptor, Esrra, to not only regulate transcription but also protein translation, via induction of Rplp1. - ArticleLuo X, Deng H, Xie F, Wang L, Liang J, Zhu X, Li T, Tang X, Liang W, Xiang Z, He J.Transl Oncol. 2024 Sep;47:101997.The liver is the most common organ for the formation of colorectal cancer metastasis. Non-invasive prognostication of colorectal cancer liver metastasis (CRLM) may better inform clinicians for decision-making. Contrast-enhanced computed tomography images of 180 CRLM cases were included in the final analyses. Radiomics features, including shape, first-order, wavelet, and texture, were extracted with Pyradiomics, followed by feature engineering by penalized Cox regression. Radiomics signatures were constructed for disease-free survival (DFS) by both elastic net (EN) and random survival forest (RSF) algorithms. The prognostic potential of the radiomics signatures was demonstrated by Kaplan-Meier curves and multivariate Cox regression. 11 radiomics features were selected for prognostic modelling for the EN algorithm, with 835 features for the RSF algorithm. Survival heatmap indicates a negative correlation between EN or RSF risk scores and DFS. Radiomics signature by EN algorithm successfully separates DFS of high-risk and low-risk cases in the training dataset (log-rank test: p < 0.01, hazard ratio: 1.45 (1.07-1.96), p < 0.01) and test dataset (hazard ratio: 1.89 (1.17-3.04), p < 0.05). RSF algorithm shows a better prognostic implication potential for DFS in the training dataset (log-rank test: p < 0.001, hazard ratio: 2.54 (1.80-3.61), p < 0.0001) and test dataset (log-rank test: p < 0.05, hazard ratio: 1.84 (1.15-2.96), p < 0.05). Radiomics features have the potential for the prediction of DFS in CRLM cases.
- ArticleZhou Z, Shin JY, Gurudu SR, Gotway MB, Liang J.Med Image Anal. 2021 07;71:101997.The splendid success of convolutional neural networks (CNNs) in computer vision is largely attributable to the availability of massive annotated datasets, such as ImageNet and Places. However, in medical imaging, it is challenging to create such large annotated datasets, as annotating medical images is not only tedious, laborious, and time consuming, but it also demands costly, specialty-oriented skills, which are not easily accessible. To dramatically reduce annotation cost, this paper presents a novel method to naturally integrate active learning and transfer learning (fine-tuning) into a single framework, which starts directly with a pre-trained CNN to seek "worthy" samples for annotation and gradually enhances the (fine-tuned) CNN via continual fine-tuning. We have evaluated our method using three distinct medical imaging applications, demonstrating that it can reduce annotation efforts by at least half compared with random selection.
- ArticleNarayan AJ, Lieberman AF, Masten AS.Clin Psychol Rev. 2021 04;85:101997.In recent years, research and practice on adverse childhood experiences (ACEs) have shifted from delineating effects of ACEs on adulthood health problems to preventing ACEs in children. Nonetheless, little attention has focused on how parents' own childhood experiences, adverse or positive, may influence the transmission of ACEs across generations. Children's risk for ACEs and potential for resilience may be linked to the early child-rearing experiences of their parents carried forward into parenting practices. Additionally, parents with multiple ACEs may have PTSD symptoms, an under-recognized mediator of risk in the intergenerational transmission of ACEs. Guided by developmental psychopathology and attachment theory with an emphasis on risk and resilience, we argue that a more comprehensive understanding of parents' childhood experiences is needed to inform prevention of ACEs in their children. Part I of this review applies risk and resilience concepts to pathways of intergenerational ACEs, highlighting parental PTSD symptoms as a key mediator, and promotive or protective processes that buffer children against intergenerational risk. Part II examines empirical findings indicating that parents' positive childhood experiences counteract intergenerational ACEs. Part III recommends clinically-sensitive screening of ACEs and positive childhood experiences in parents and children. Part IV addresses tertiary prevention strategies that mitigate intergenerational ACEs and promote positive parent-child relationships.
- ArticleTamplin J, Thompson Z.Arts Psychother. 2023 Feb;82:101997.The COVID-19 pandemic significantly impacted the operation of choirs around the world due to the high-risk nature of group singing for disease transmission. These risks are even greater for people living with health conditions. This paper presents the results of an international, cross-sectional survey that asked health-focused choir facilitators if and how they adapted their choir to due to COVID-19 restrictions and the high-risk of transmission during group singing. Participants were recruited through searches of choir and music therapy networks, social media, and snowballing sampling methods. The anonymous online survey consisted of 17 multiple choice and 7 short answer questions. Data was analysed using descriptive statistics and thematic analysis. Sixty-five surveys were commenced (50 completed). Many respondents (63 %) took their choirs online, and neurological conditions were the most common populations served. Format and methods of online choirs are described, as are benefits and challenges of online choirs. Several respondents indicated they would continue online post-COVID-19 restrictions. Online choirs were seen as feasible and beneficial, despite challenges. Recommendations regarding facilitator skills, technology set up, accessibility and session structure for online facilitation of health-focused choirs are provided.
- ArticleGe N, Liu M, Krawczyk J, McInerney V, Ward D, Shen S, O'Brien T, Prendiville T.Stem Cell Res. 2020 12;49:101997.Long QT syndrome (LQTS), an inherited cardiac ion channelopathy, is associated with ventricular arrhythmias and risk of sudden death. LQTS sub-type 2 (LQT2) is caused by pathogenic variants in KCNH2 encoding the α-subunit of Kv11.1, thus affecting the rapid component of delayed rectifier K+ current (IKr) channel during the action potential. In this study, non-integrational Sendai reprogramming method was used to generate an induced-pluripotent-stem-cell (iPSC) line carrying the KCNH2 c.2464G>A (p.Val822Met) pathogenic variant from a LQT2 patient. This patient-specific iPSC line NUIGi003-A harbouring the c.2464G>A variant expressed pluripotency markers and demonstrated the differentiation potential to all three germ layers.
- ArticleKondo T, Takahashi M, Yamasaki G, Sugimoto M, Kuse A, Morichika M, Nakagawa K, Sakurada M, Asano M, Ueno Y.Leg Med (Tokyo). 2022 Feb;54:101997.von Willebrand factor (VWF) plays a crucial role in hemostasis and thrombosis. VWF is involved in platelet attachment to the subendothelium, serving as a carrier protein for coagulation factor VIII. In this study, myocardial tissues from deceased patients with ischemic heart disease and a mouse model of acute myocardial infarction were subjected to immunohistochemistry to determine VWF expression. We examined 28 neutral formalin-fixed, paraffin-embedded myocardial tissue samples obtained from the autopsies of patients who were diagnosed with ischemic heart disease within 48 h postmortem. Most myocardial cells were negative for VWF, although some cells showed nonspecific positivity. Elevated VWF expression was observed around myocardial cells undergoing remodeling, suggesting that endothelial proliferation occurred at these sites. In contrast, completely fibrotic myocardial foci did not show upregulated VWF expression. Positivity in fibrin deposition and hemorrhagic sites was observed. The same VWF expression characteristics as those observed in the human samples were observed in the mouse model. VWF immunostaining as an endothelial marker may be a useful supplementation to conventional staining techniques that are currently used in the diagnosis of ischemic heart disease in terms of examining the timing of myocardial remodeling in detail and highlighting the remodeling process.
- ArticleSamadi Takaldani AH, Javanshir N, Mansour A, Salmani A, Negaresh M.Respir Med Case Rep. 2024;48:101997.Hemoptysis is a common clinical symptom in emergency patients. It is characterized by the discharge of bloody sputum, which originates from the lower respiratory tract. In the majority of cases, this event is self-limiting, and only in less than 5% of cases, it is massive. Mitral valve stenosis is an uncommon cause of hemoptysis, with a prevalence of 4.2%. In rare cases of this condition, massive and sudden hemoptysis occurs, which is called pulmonary apoplexy. Here, a 35-year-old woman with a history of mitral valve stenosis is introduced who was referred to the hospital with a complaint of massive hemoptysis and sudden shortness of breath. According to the history of mitral valve stenosis, the patient was diagnosed with pulmonary apoplexy. After treatment, both the imaging findings and the patient's symptoms resolved within a short period of time. Even though pulmonary apoplexy is often severe, it can still respond well to conservative treatments and may indicate a need for immediate attention to the stenosis of the mitral valve.
- ArticleGarcia-Ortega DY, Ortega Jiménez JA, Melendez-Fernandez AP, Álvarez-Cano A, Caro-Sanchez CHS, Vargas-Lara AK, Luna-Ortiz K.Surg Oncol. 2023 Dec;51:101997.BACKGROUND: The treatment of choice for retroperitoneal soft tissue sarcomas (RPS) is surgical resection; the outcomes with more radical surgeries, notably compartmental resection, remains a subject of debate. Arguments against it, include the complexity of the technique and high morbidity.
MATERIALS AND METHODS: A retrospective analysis of cases treated in a single center from January 2010 to December 2019 is presented. Two time periods were evaluated: 2010-2015 and 2016-2019, corresponding to before and after the implementation of routine compartmentectomy. We evaluated the short- and long-term outcomes of compartmental resection compared to limited surgeries through a multivariate analysis of prognostic factors.
RESULTS: A total of 176 cases were included, of which 102 met the inclusion criteria. The sex distribution was similar. The average age was 52.9 years, and the average tumor size was 24.5 cm. The most frequent histology was liposarcoma (65.7%), followed by leiomyosarcoma (12.7%), and malignant peripheral nerve sheath tumor (8.8%). The median follow-up period was 40 months. We found a lower local recurrence in the group treated in the recent period (compartmentectomy) 42.3% vs 20% p = 0.007. The median overall survival (OS) was 38.7 months, and there was no difference in distant recurrence between the two time periods. Postoperative morbidity was higher in the recent period (25% vs 10% p 0.041), with no difference in 30-day mortality.
CONCLUSIONS: The implementation of extensive surgery, specifically compartmentectomy, for retroperitoneal sarcomas has been linked to reduced local recurrence. We recommend considering this surgical approach for RPS in alignment with current expert consensus guidelines, as highlighted by the updated TARPSWG consensus. - ArticleAzuma N, Omachi S, Hanazawa W, Morimoto A, Sanjoba C, Matsumoto Y, Fujii W, Goto Y.Parasitol Int. 2020 Feb;74:101997.B-cell activating factor (BAFF) is known as a cytokine responsible for survival and activation of B cells. However, involvement of the molecule in IgG antibody production during infection remains elusive. In this study, dependency of antibody production in Leishmania infection on BAFF was examined by using BAFF-knockout (BAFF-KO) mice. When BAFF-KO mice were infected with L. major, there was no significant difference in lesion development or parasite burden from those in infected wildtype mice. In contrast, levels of IgG antibodies to Leishmania crude antigen were lower in BAFF-KO mice, suggesting that antibody production during L. major infection is BAFF-dependent. ELISA using defined leishmanial antigens demonstrated that the influence of BAFF on antibody production during L. major varies depending on antigens; IgG production to tandem repeat proteins were more affected by BAFF than non-repeat antigens. On the contrary, all of the defined antigens tested were strongly affected by BAFF for IgG antibody production during L. donovani infection. These results suggest degree of BAFF contribution to antibody production during infection is variable depending on the type of infection and even on the type of antigen in a given infection. These results may explain contradictory roles of BAFF in antibody production in previous works.
- ArticleWang Y, Zhang W, Ye H, Xiao Y.Sleep Med Rev. 2024 Dec;78:101997.There remains an unmet need for a targeted treatment to address residual excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA) after primary treatment. This network meta-analysis evaluated the efficacy and safety of wake-promoting agents (WPAs), namely solriamfetol, pitolisant, modafinil, and armodafinil, for treating residual EDS in patients with OSA. We conducted a comprehensive search which ultimately included 18 studies in the final analysis. All 4 WPAs demonstrated significant therapeutic benefits for the Epworth sleepiness scale (ESS) and maintenance of wakefulness test (MWT). Based on the surface under the cumulative ranking curve (SUCRA) score, solriamfetol, pitolisant, modafinil and armodafinil were ranked from highest to lowest for the ESS. A similar ranking was observed for MWT, where pitolisant was not included in the analysis. The subgroup analysis also evaluated the efficacy of WPAs in the primary treatment adherent and nonadherent subgroups. Regarding adverse reactions, solriamfetol demonstrated the lowest risk of all-cause discontinuation, whereas pitolisant exhibited minimal risks of adverse events leading to treatment discontinuation and treatment-emergent adverse events. Our analysis comprehensively compared the effects and adverse reactions of different WPAs in treating residual EDS in treated patients with OSA. This has significant implications for the practical clinical use of WPAs and future research.