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Abstract This study aims to consolidate the available knowledge on gender diversity and its impact on the dual performance (social and financial) of Microfinance Institutions (MFIs). We specifically focus on MFIs due to their distinctive nature compared to other industries, being traditionally women-centered and having a substantial representation of women employees across all levels of the corporate hierarchy. To conduct this comprehensive analysis, we employed a systematic review approach, meticulously selecting 24 relevant papers from the Scopus and Web of Science databases. Our findings revealed that research on gender diversity in MFIs primarily focuses on the board level. However, existing studies present conflicting results, suggesting that the impact of gender diversity on MFI performance is nuanced and complex. This complexity stems largely from the varying roles women play within the organizational structure. Furthermore, our analysis highlights the influence of additional factors, such as the database used, the study's context, and its geographical location, on the reported outcomes. Notably, research on gender diversity at the managerial and loan officer levels remains scarce, presenting a significant gap in the current body of knowledge. To further illuminate this field, this study identifies the most influential papers on the topic of gender diversity in microfinance. Additionally, we provide a co-authorship network analysis, visualizing the connections between existing research. This analysis provides valuable insights and inspiration for future research endeavors in this critical area.

Abstract In the last decade, clinical studies have investigated the clinical relevance of circulating cell-free-DNA (ccfDNA) as a diagnostic and prognosis tool in various diseases including cancers. However, limited knowledge on ccfDNA biology restrains its full development in the clinical practice. To improve our understanding, we evaluated the impact of the circadian rhythm on ccfDNA release in healthy subjects over a 24-h period. 10 healthy female subjects underwent blood sampling at 8am and 20 healthy male subjects underwent serial blood sampling (8:00 AM, 9:00 AM, 12:00 PM, 4:00 PM, 8:00 PM, 12:00 AM, 4 AM (+ 1 Day) and 8 AM (+ 1 Day)). We performed digital droplet-based PCR (ddPCR) assays to target 2 DNA fragments (69 & 243 bp) located in the KRAS gene to determine the ccfDNA concentration and fragmentation profile. As control, half of the samples were re-analyzed by capillary miniaturized electrophoresis (BIAbooster system). Overall, we did not detect any influence of the circadian rhythm on ccfDNA release. Instead, we observed a decrease in the ccfDNA concentration after meal ingestion, suggesting either a post-prandial effect or a technical detection bias due to a higher plasma load in lipids and triglycerides. We also noticed a potential effect of gender, weight and creatinine levels on ccfDNA concentration.

Background. Metabolic dysfunction-associated steatohepatitis (MASH) has become the leading cause of chronic liver disease, but there has been no approved pharmacotherapy to date. Methods. We used a network analysis approach to delineate protein-protein interactions that contribute to the transition from steatosis to MASH, in order to identify and target this transition as a potential pharmacotherapeutic strategy. Acyl-CoA thioesterase 1 (ACOT1) was identified as a critical node in the protein-protein interaction (PPI) network of the transition from steatosis to MASH in patient samples. ACOT1 overexpression and silencing effects were tested in vivo on C57BL/6 mice exposed to high-fat diet (HFD) and inoculated with an adenoviral system to modulate ACOT1 expression. Transcriptomic and untargeted lipidomic profiles were performed on the mouse livers. Results. ACOT1 expression was 3-fold higher in MASH as compared to steatosis. In patient samples, ACOT1 was significantly correlated with the severity of MASH as reflected by the nonalcoholic fatty liver disease score. Experimental validation showed that downregulation of ACOT1 resulted in decreased lipid accumulation and prevention of MASH in vivo. Conversely, upregulation of ACOT1 via an adenoviral vector resulted in development of MASH, whereas control mice only developed steatosis. Lipidomic analysis revealed glycerophospholipids to be especially abundant in MASH accelerated by ACOT1 upregulation. Conclusion. These results suggest that ACOT1 contributes to the transition from steatosis to MASH through modulation of glycerophospholipid accumulation and its potential as a novel therapeutic target in MASH. This trial is registered with NCT02148471.

BackgroundNon-alcoholic steatohepatitis (NASH) has become a leading indication for liver transplantation. However, it often recurs in the graft and can also arise de novo in individuals transplanted for other indications. Post-transplant NASH (PT-NASH) is more aggressive and leads to accelerated fibrosis. The mechanistic basis of PT-NASH has not yet been defined and no specific therapeutic strategies are currently available.MethodsHere, we profiled the transcriptomes of livers with PT-NASH from liver transplant recipients to identify dysregulated genes, pathways, and molecular interaction networks.ResultsTranscriptomic changes in the PI3K-Akt pathway were observed in association with metabolic alterations in PT-NASH. Other significant changes in gene expression were associated with DNA replication, cell cycle, extracellular matrix organization, and wound healing. A systematic comparison with non-transplant NASH (NT-NASH) liver transcriptomes indicated an increased activation of wound healing and angiogenesis pathways in the post-transplant condition.ConclusionBeyond altered lipid metabolism, dysregulation of wound healing and tissue repair mechanisms may contribute to the accelerated development of fibrosis associated with PT-NASH. This presents an attractive therapeutic avenue to explore for PT-NASH to optimize the benefit and survival of the graft.

Abstract SARS‐CoV‐2 infection hijacks signaling pathways and induces protein–protein interactions between human and viral proteins. Human genetic variation may impact SARS‐CoV‐2 infection and COVID‐19 pathology; however, the genetic variation in these signaling networks remains uncharacterized. Here, we studied human missense single nucleotide variants (SNVs) altering phosphorylation sites modulated by SARS‐CoV‐2 infection, using machine learning to identify amino acid substitutions altering kinase‐bound sequence motifs. We found 2,033 infrequent phosphorylation‐associated SNVs (pSNVs) that are enriched in sequence motif alterations, potentially reflecting the evolution of signaling networks regulating host defenses. Proteins with pSNVs are involved in viral life cycle and host responses, including RNA splicing, interferon response (TRIM28), and glucose homeostasis (TBC1D4) with potential associations with COVID‐19 comorbidities. pSNVs disrupt CDK and MAPK substrate motifs and replace these with motifs of Tank Binding Kinase 1 (TBK1) involved in innate immune responses, indicating consistent rewiring of signaling networks. Several pSNVs associate with severe COVID‐19 and hospitalization (STARD13, ARFGEF2). Our analysis highlights potential genetic factors contributing to inter‐individual variation of SARS‐CoV‐2 infection and COVID‐19 and suggests leads for mechanistic and translational studies.

We use a database composed of 2,545 Microfinance Institutions (MFIs) worldwide for the period 2008–18 to explore the effect of a larger share of women's workforce on both staff wages and overall monetary compensation within MFIs. MFIs are different from other industries, as they are traditionally women‐centered, i.e. they have a significant share of women employees at every level of the corporate hierarchy and mostly serve women clients. Applying both traditional estimation methodology and techniques aimed at accounting for possible endogeneity among the main variables, we find that a higher proportion of women on staff significantly increases the average expense per worker (which also includes the incentive components of remuneration) while the effects are considerably smoothed (or not significant) on the base salary. This leads us to conclude that, unlike what is seen in other sectors of the economy, MFIs do not pay women less. Yet, significant positive effects of women in the workforce, especially on average overall monetary compensation, suggest that women are likely to exploit their superior skills and/or gender affinity advantages with customers of the same gender to enhance MFIs' efficiency and profitability, thereby achieving higher incentive compensation, mostly in the form of bonuses and other benefits. [ABSTRACT FROM AUTHOR]

This study aimed to report cancer incidence and mortality in a Brazilian human immunodeficiency virus (HIV) cohort of 31?years duration and compare cancer deaths with deaths due to noncancer causes. We also investigated risk factors for the development of acquired immunodeficiency syndrome (AIDS)-defining and non-AIDS-defining cancers. We searched for any information related to the diagnosis of cancer in a period ranging from 1989 to 2020. We also collected data on sociodemographic and clinical information and risk factors. Statistical analysis included parametric and nonparametric tests and the building of survival curves. We used the statistical software GraphPad software (version 9) and STATA software (version 14) for the elaboration of statistics. Fifty-five new cases of cancer occurred in a total of 677 HIV patients included in our cohort over 31?years, an incidence of 8.12%. The most important risk factors associated with cancer were smoking (p = 0.03), infection with oncoviruses like human papillomavirus (p < 0.001), and hepatitis C (p = 0.04). Eleven patients (1.6%) died from cancer. The most frequent diagnoses of fatal cancer were liver cancer and lymphoma (three cases each). The mean follow-up time of patients dying from cancer was 14?years; patients dying from noncancer causes were 24 (3.55%), and their mean follow-up time was 11?years. We had low overall mortality in our cohort of HIV patients (5.2%), mostly due to noncancer causes, which may be due to the fact that most of our patients begin follow-up asymptomatic. Cancer deaths were 31.4% of all deaths; half of those cancers were AIDS-defining.

Background. Metabolic dysfunction‐associated steatohepatitis (MASH) has become the leading cause of chronic liver disease, but there has been no approved pharmacotherapy to date. Methods. We used a network analysis approach to delineate protein‐protein interactions that contribute to the transition from steatosis to MASH, in order to identify and target this transition as a potential pharmacotherapeutic strategy. Acyl‐CoA thioesterase 1 (ACOT1) was identified as a critical node in the protein‐protein interaction (PPI) network of the transition from steatosis to MASH in patient samples. ACOT1 overexpression and silencing effects were tested in vivo on C57BL/6 mice exposed to high‐fat diet (HFD) and inoculated with an adenoviral system to modulate ACOT1 expression. Transcriptomic and untargeted lipidomic profiles were performed on the mouse livers. Results. ACOT1 expression was 3‐fold higher in MASH as compared to steatosis. In patient samples, ACOT1 was significantly correlated with the severity of MASH as reflected by the nonalcoholic fatty liver disease score. Experimental validation showed that downregulation of ACOT1 resulted in decreased lipid accumulation and prevention of MASH in vivo. Conversely, upregulation of ACOT1 via an adenoviral vector resulted in development of MASH, whereas control mice only developed steatosis. Lipidomic analysis revealed glycerophospholipids to be especially abundant in MASH accelerated by ACOT1 upregulation. Conclusion. These results suggest that ACOT1 contributes to the transition from steatosis to MASH through modulation of glycerophospholipid accumulation and its potential as a novel therapeutic target in MASH. This trial is registered with NCT02148471. [ABSTRACT FROM AUTHOR]

Considering the importance of promoting gender equality, Microfinance Institutions (MFIs) have emerged to reduce the gender gap by supplying credit opportunities to women. However, the microfinance literature has largely focused on the role of women in the client base while devoting less attention to their representation in the organizational structure of MFIs. This study aims to fill this gap. Using ANOVA and random effects models, our purpose is to investigate which types of MFIs more intensively promote gender equality within their workforce, at any of the organizational ladders. We analyze data from 1222 MFIs across 102 developing countries from 2010 to 2018. Empirical evidence reveals that the presence of females in both the workforce and the client base is significantly lower in commercially motivated MFIs (e.g., banks and other for‐profit institutions) compared to non‐government organizations (NGOs), and —to a lesser extent— credit unions, cooperatives and rural banks. Our results suggest that the microfinance sector would benefit from a stronger emphasis on NGO‐driven initiatives to promote female representation in terms of both employment opportunities and access to credit. [ABSTRACT FROM AUTHOR]

Abstract We think that thalassemia is not necessarily a cause of aggravation of the clinical course in COVID‐19; however, certain key factors must be considered, such as the anemic condition, the likely pathogenic role of the virus on hemoglobin, and the hypercoagulable state to prevent any complications.

Objetivo: Identificar as estruturas das farmácias hospitalares e a atuação do farmacêutico hospitalar no Estado de São Paulo. Métodos: Trata-se de um estudo transversal, desenvolvido pelo Grupo Técnico de Trabalho de Farmácia Hospitalar do CRF-SP por encaminhamento de e-mails para os Farmacêuticos do Estado de São Paulo e divulgação no Portal do CRF-SP no período de outubro de 2018 a fevereiro de 2019, o instrumento de coleta foi um questionário no formato Google Docs contendo 55 questões abordando os aspectos caracterização geral do hospital, farmácia hospitalar e do farmacêutico. Os dados qualitativos foram tabulados em planilha Excel e analisados por frequência absoluta e relativa sendo apresentados em formas de tabelas. Foi utilizado os testes estatísticos não paramétricos com o valor de p< 0.05 e o intervalo de confiança de 95% pelo sistema JAMOVI (versão 1.6.23). Resultados: Participaram da pesquisa 434 farmacêuticos representando 4,8% com atividade laboral na área hospitalar. Observa-se que administração da área hospitalar está mais relacionada ao serviço privado na administração própria 173 (45,9%) (p< 0,001), o segmento com o hospital de especialidades 246 (65,3%) (p< 0,001), especialidades com oncologia 40 (14,9%) (p= 1,000), contribuindo com decisões estratégicas, táticas e operacionais, aprimorando as estruturas técnicas e o fortalecimento do serviço de saúde e as atividades dos farmacêuticos relacionados a orientação de alta com 148 (48,5%) (p< 0,001), intervenção nas prescrições 236 (77,4%) (p< 0,001), visita multidisciplinar 229 (75,1%) (p< 0,001), conciliação medicamentosa 220 (72,1%). Conclusão: Observamos o desafio e a necessidade de aprimorar o estreitamento da comunicação entre os profissionais e a entidade, e às novas tecnologias poderão aproximar e estimular uma dinâmica produtiva da categoria.

"Sim Sala Bim!" —Silvan, https://en.wikipedia.org/wiki/Silvan%5f(illusionist) Betweenness centrality is a popular centrality measure with applications in several domains and whose exact computation is impractical for modern-sized networks. We present SILVAN, a novel, efficient algorithm to compute, with high probability, accurate estimates of the betweenness centrality of all nodes of a graph and a high-quality approximation of the top-k betweenness centralities. SILVAN follows a progressive sampling approach and builds on novel bounds based on Monte Carlo Empirical Rademacher Averages, a powerful and flexible tool from statistical learning theory. SILVAN relies on a novel estimation scheme providing non-uniform bounds on the deviation of the estimates of the betweenness centrality of all the nodes from their true values and a refined characterisation of the number of samples required to obtain a high-quality approximation. Our extensive experimental evaluation shows that SILVAN extracts high-quality approximations while outperforming, in terms of number of samples and accuracy, the state-of-the-art approximation algorithm with comparable quality guarantees. [ABSTRACT FROM AUTHOR]

Background: Cellular-cell free-DNA (ccfDNA) is being explored as a diagnostic and prognostic tool for various diseases including cancer. Beyond the evaluation of the ccfDNA mutational status, its fragmentation has been investigated as a potential cancer biomarker in several studies. However, probably due to a lack of standardized procedures dedicated to preanalytical and analytical processing of plasma samples, contradictory results have been published.Methods: ddPCR assays allowing the detection of KRAS wild-type and mutated sequences (KRAS p.G12V, pG12D, and pG13D) were designed to target different fragments sizes. Once validated on fragmented and non-fragmented DNA extracted from cancer cell lines, these assays were used to investigate the influence of the extraction methods on the non-mutated and mutated ccfDNA integrity reflected by the DNA integrity index (DII). The DII was then analyzed in two prospective cohorts of metastatic colorectal cancer patients (RASANC study n = 34; PLACOL study n = 12) and healthy subjects (n = 49).Results and Discussion: Our results demonstrate that ccfDNA is highly fragmented in mCRC patients compared with healthy individuals. These results strongly suggest that the characterization of ccfDNA integrity hold great promise toward the development of a universal biomarker for the follow-up of mCRC patients. Furthermore, they support the importance of standardization of sample handling and processing in such analysis.

Deciphering the functional impact of genetic variation is required to understand phenotypic diversity and the molecular mechanisms of inherited disease and cancer. While millions of genetic variants are now mapped in genome sequencing projects, distinguishing functional variants remains a major challenge. Protein-coding variation can be interpreted using post-translational modification (PTM) sites that are core components of cellular signaling networks controlling molecular processes and pathways. ActiveDriverDB is an interactive proteo-genomics database that uses more than 260,000 experimentally detected PTM sites to predict the functional impact of genetic variation in disease, cancer and the human population. Using machine learning tools, we prioritize proteins and pathways with enriched PTM-specific amino acid substitutions that potentially rewire signaling networks via induced or disrupted short linear motifs of kinase binding. We then map these effects to site-specific protein interaction networks and drug targets. In the 2021 update, we increased the PTM datasets by nearly 50%, included glycosylation, sumoylation and succinylation as new types of PTMs, and updated the workflows to interpret inherited disease mutations. We added a recent phosphoproteomics dataset reflecting the cellular response to SARS-CoV-2 to predict the impact of human genetic variation on COVID-19 infection and disease course. Overall, we estimate that 16-21% of known amino acid substitutions affect PTM sites among pathogenic disease mutations, somatic mutations in cancer genomes and germline variants in the human population. These data underline the potential of interpreting genetic variation through the lens of PTMs and signaling networks. The open-source database is freely available at www.ActiveDriverDB.org.

A instabilidade de vertentes está presente sobretudo em regiões montanhosas e serranas com declives elevados, mas o crescimento urbano desordenado em áreas suscetíveis, somado à falta de ordenamento do uso do solo, tem aumentado a ocorrência de desastres relacionados com estes processos também em espaços urbanos. O estudo climático se faz necessário para acompanhamento e prevenção dos movimentos em massa, já que eles são, quase sempre, deflagrados por eventos de precipitação extrema e/ou de longa duração. Um banco de dados é uma ferramenta importante para a contribuição destes estudos e para a gestão de riscos.

We examine the contribution of trade to the rise of modern agriculture, taking into account interactions between trade, input requirements, and technology adoption. We develop and estimate a new multicountry general equilibrium model that incorporates producers' choices of which crops to produce and with which technologies at the level of grid cells covering the earth's surface. We find that trade cost reductions in agricultural inputs and the international transmission of productivity growth in the agricultural input sector since the 1980s induced large shifts from traditional, labor-intensive technologies to modern, input-intensive ones, with important global and distributional implications for productivity and welfare. [ABSTRACT FROM AUTHOR]

This article supports the view that, while judges suppress dissent when dissenting is too costly, the cost of dissenting depends on the political dimension of the issue broached. It contends that judges who disagree may nevertheless try to safeguard integrity and legitimacy in political disputes by presenting a public impression of unity. We muster evidence from the United Kingdom, specifically, votes from the Judicial Committee of the Privy Council (JCPC) between 1998 and 2011. We demonstrate through statistical analysis that judges are likelier to suppress dissent in devolution cases, which are characterized to be more political in character, than in Commonwealth appeals, which are more mundane in nature. We find that, while consensus on domestic issues reflects the absence of disagreement across judicial ideologies, judges have stronger conflicting positions on issues concerning devolution, but tend to suppress their propensity to dissent. This finding confirms that the JCPC wants to appear cohesive to give an image of greater authority on decisions of predominantly political content. [ABSTRACT FROM AUTHOR]

Sepsis is an especially common affliction in the elderly and despite its increased prevalence and mortality in older people, the immune response of the elderly during septic shock appears similar to that of younger patients. In the original study we conducted a global gene expression analysis of circulating neutrophils from elderly and young septic patients, as well as from age-matched healthy controls, to better understand how elder individuals respond to severe infectious insult (Pellegrina et al., 2015). Here we provide additional details pertaining processing and statistical analysis of the microarray data. Raw and normalized datasets linked to this project have been deposited in the Gene Expression Omnibus (GEO) database under accession number GSE67652.