bluuebunny/crossref_metadata_2025_split huggingface dataset:
Demographic and professional risk factors of COVID-19 infections among physicians in low- and middle-income settings; findings from a representative survey in two Brazilian states
Authors: Russo Giuliano , Cassenote Alex , de Oliveira Bruno Luciano Carneiro Alves , Scheffer Mario 
Published: May 2022

AbstractIntroductionHealth workers (HWs) are a key resource for health systems worldwide, and have been affected heavily by the COVID-19 pandemic. Evidence is consolidating on incidence and associated drivers of infections, predominantly in high-income settings. It is however still unclear what the risk factors may be for specific health professions, particularly in low- and middle-income countries (LMICs).MethodsWe conducted a cross-sectional survey in a representative sample of 1,183 medical doctors registered with Brazil’s Federal Council of Medicine in one developed (São Paulo) and one disadvantaged state (Maranhão). Between February-June 2021, we administered a telephone questionnaire to collect data on physicians’ demographics, deployment to services, vaccination status, and self-reported COVID-19 infections. We performed descriptive, univariate, and multilevel clustered analysis to explore the association between physicians’ infection rates, and their sociodemographic and employment characteristics. A generalized linear mixed model with a binomial distribution was used to estimate the adjusted odds ratio.ResultsWe found that 35.8% of physicians in our sample were infected with COVID-19 in the first year of the pandemic. The infection rate in Maranhão (49.2%) [95% CI 45.0-53.4] was almost twice that in São Paulo (24.1%) [95% CI 20.8-27.5]. Being a physician in Maranhão [95% CI 2.08-3.57], younger than 50 years [95% CI 1.41-2.89], and having worked in a COVID-19 ward [95% CI 1.28-2.27], were positively associated with the probability of infections. Conversely, working with diagnostic services [95% CI 0.53-0.96], in administrative functions [95% CI 0.42-0.80], or in teaching and research [95% CI 0.48-0.91] was negatively associated.ConclusionsBased on data from Brazil, COVID-19 infections in LMICs may be more likely in those health systems with lower physician-to-patient ratios, and younger doctors working in COVID-19 wards may be infected more frequently. Such findings may be used to identify policies to mitigate COVID-19 effects on HWs in LMICs.
The Role of Mitochondrial genome abundance in Alzheimer’s Disease
Authors: Harerimana Nadia V. , Paliwali Devashi , Romero-Molina Carmen , Bennett David A. , Pa Judy , Goate Alison , Swerdlow Russell H. , Andrews Shea J. 
Published: May 2022

ABSTRACTMitochondrial dysfunction is an early and prominent feature of Alzheimer’s disease (AD), with impaired energy metabolism preceding the onset of clinical symptoms. Here we propose an update to the mitochondrial dysfunction hypothesis of AD based on recent results examining the role of mitochondrial genome abundance in AD. In a large post-mortem study, we show that lower brain mitochondrial genome abundance is associated with a greater odds of AD neuropathological change and worse cognitive performance. We hypothesize that lower mitochondrial genome abundance impairs mitochondrial function by reducing mitochondrial bioenergetics, thereby impacting neuronal and glial cell function. However, it remains to be determined if mitochondrial dysfunction causes, mediates, or is a by-product of AD pathogenesis. Additional support for this hypothesis will be generated by linking peripheral blood mitochondrial genome abundance to AD and establishing clinical trials of compounds that upregulate total mitochondrial genome abundance or boost mitochondrial mass.RESEARCH IN CONTEXTSystematic ReviewThe authors used PubMed to review the literature on mitochondrial genomics in Alzheimer’s disease (AD) using the following search term:mitochondria* AND (“copy number” OR heteroplasmy OR haplogroup*) AND“Alzheimer’s disease”. The accumulated evidence suggested that increased mitochondrial genome abundance is neuroprotective, but found conflicting evidence for the association of mitochondrial heteroplasmy or specific haplogroups with AD.InterpretationWe found that higher mtDNA abundance was robustly associated with reduced AD neuropathology burden and higher neurocognitive performance. Given these findings, we propose an updated hypothesis for mitochondrial dysfunction in AD: that mitochondrial genome abundance is a relevant mechanism in AD pathogenesis. We postulate that baseline mtDNA abundance itself contributes to baseline mitochondrial function and lifetime risk, and that propensity and sensitivity to mtDNA depletion further modulate risk, histopathology, and clinical decline.Future directionsUsing statistical genetics approaches, examining the association of peripheral mtDNA abundance with AD, and upregulating mtDNA abundance, would further strengthen the evidence of a causal role for mtDNA abundance and mitochondrial dysfunction in AD pathogenesis
Bacterial contamination of Healthcare workers’ mobile phones in Africa: a systematic review and meta-analysis
Authors: Zenbaba Demisu , Sahiledengle Biniyam , Beressa Girma , Desta Fikreab , Teferu Zinash , Nugusu Fikadu , Atlaw Daniel , Shiferaw Zerihun , Mamo Ayele , Negash Wogane , Negash Getahun , Mama Mohammedaman , Nigussie Eshetu , Chattu Vijay Kumar 
Published: May 2022

AbstractBackgroundMobile phones are potential reservoirs for pathogens and sources of healthcare-associated illnesses. More microbes can be found on a mobile phone than on a man’s lavatory seat, the sole of a shoe, or a door handle. When examining patients, frequent handling of mobile phones can spread bacteria and provide a suitable breeding environment for numerous microorganisms. Nevertheless, evidence of bacterial contamination of mobile phones among healthcare workers in Africa was not conclusive. Thus, this meta-analysis and systematic review was conducted to estimate the pooled prevalence of bacterial contamination of mobile phones used by healthcare workers and the most frequent bacterial isolates in Africa.MethodsWe systematically retrieved relevant studies using PubMed/MEDLINE, Scopus, POPLINE, HINARI, Science Direct, Cochrane Library databases, and Google Scholar from 2009 to 2021 publication year. We included observational studies that reported the prevalence of bacterial contamination of mobile phones among healthcare workers. Two independent authors assessed the quality of the studies. The DerSimonian-random Laird’s effect model was used to calculate effect estimates for the pooled prevalence of bacterial contamination in mobile phones, as well as a 95% confidence interval (CI).ResultsAmong 3882 retrieved studies, 23 eligible articles with a total sample size of 2,623 study participants were included in the meta-analysis. The pooled prevalence of mobile phones bacterial contamination among healthcare workers was 83.9% (95% CI: 80.6, 87.2%; I2= 98%, p-value < 0.001). The most dominant type of bacteria isolated in this review wascoagulase-negative staphylococci(CONS) which accounted for 44.5% of the pooled contamination rate of mobile phones used by healthcare workers, followed byStaphylococcus aureus(32.3%), andEscherichia coli(8.4%).ConclusionThe review indicated that the contamination with a different bacterial isolate of mobile phones used by health care workers was high. The most dominant bacterial isolates wereCoagulase-negative staphylococci, Staphylococcus aureus, andEscherichia coli. Hence, these findings would have implications for policymakers and resource allocation for preventive measures initiatives.
Pilot study to evaluate hypercoagulation and inflammation using rotational thromboelastometry and calprotectin in COVID-19 patients
Authors: Stanford S.N. , Roy A. , Rea C. , Harris Ben , Ashton A. , Mangles S. , Everington T. , Taher R. , Burns D. , Arbuthnot E. , Cecil T. 
Published: May 2022

AbstractIntroductionAbnormal coagulation and inflammation are hallmarks of SARs-COV-19. Stratifying affected patients on admission to hospital may help identify those who are risk of developing severe disease early on. ROTEM is a point of care test that can be used to measure abnormal coagulation and calprotectin is a measure of inflammation.AimAssess if ROTEM can measure hypercoagulability on admission and identify those who will develop severe disease early on. Assess if calprotectin can measure inflammation and if there is a correlation with ROTEM and calprotectin.MethodsCOVID-19 patients were recruited on admission and ROTEM testing was undertaken daily for a period of 7 days. Additionally inflammatory marker calprotectin was also tested.Results33 patients were recruited to the study out of which 13 were admitted to ITU and 20 were treated on the ward. ROTEM detected a hypercoagulable state on admission but did not stratify between those admitted to a ward or escalated to ITU. Calprotectin levels were raised but there was no statistical difference (p=0.73) between groups. Significant correlations were observed between FIBA5 (p<0.00), FIBCFT (p<0.00), FIBMCF (p<0.00) and INMCF (p<0.00) and calprotectin.ConclusionCOVID19 patients were hypercoagulable in admission. The correlations between ROTEM and calprotectin underline the interactions between inflammation and coagulation.
The cost-effectiveness of small-quantity lipid-based nutrient supplements for prevention of child death and malnutrition and promotion of healthy development: modeling results for Uganda
Authors: Adams Katherine P , Vosti Stephen A , Arnold Charles D , Engle-Stone Reina , Prado Elizabeth L , Stewart Christine P , Wessells K Ryan , Dewey Kathryn G 
Published: May 2022

AbstractObjectiveRecent meta-analyses demonstrate that small-quantity lipid-based nutrient supplements (SQ-LNS) for young children significantly reduce child mortality, stunting, wasting, anemia and adverse developmental outcomes. Cost considerations should inform policy decisions. We developed a modeling framework to estimate the cost and cost-effectiveness of SQ-LNS and apply the framework in the context of rural Uganda.DesignWe adapted costs from a costing study of micronutrient powder (MNP) in Uganda, and based effectiveness estimates on recent meta-analyses and Uganda-specific estimates of baseline mortality and the prevalence of stunting, wasting, anemia, and developmental disability.SettingRural Uganda.ParticipantsNot applicable.ResultsProviding SQ-LNS daily to all children in rural Uganda (>1 million) for 12 months (from 6-18 months of age) via the existing Village Health Team system would cost ∼$52 per child (2020 US dollars), or ∼$58.7 million annually. Annually, SQ-LNS could avert an average of >242,000 disability adjusted life years (DALYs) as a result of preventing 3,689 deaths, >160,000 cases of moderate or severe anemia, and ∼6,000 cases of developmental disability. The estimated cost per DALY averted is $242, which is considered “very cost effective” relative to the Uganda per capita GDP of $822.ConclusionsIn this context, SQ-LNS may be more cost-effective than other options such as MNP or the provision of complementary food, although the total cost for a program including all age-eligible children would be high. Strategies to reduce costs, such as targeting to the most vulnerable populations and the elimination of taxes on SQ-LNS, may enhance financial feasibility.
The Glycan-Specificity of the Pineapple Lectin AcmJRL and its Carbohydrate-Dependent Binding of the SARS-CoV-2 Spike Protein
Authors: Meiers Joscha , Dastbaz Jan , Adam Sebastian , Rasheed Sari , Kirsch Susanne H. , Meiser Peter , Gross Peter , Müller Rolf , Titz Alexander 
Published: May 2022

AbstractThe current SARS-CoV-2 pandemic has become one of the most challenging global health threats, with over 530 million reported infections by May 2022. In addition to vaccines, research and development have also been directed towards novel drugs. Since the highly glycosylated spike protein of SARS-CoV-2 is essential for infection, it constitutes a prime target for antiviral agents. The pineapple-derived jacalin-related lectin (AcmJRL) is present in the medication bromelain in significant quantities and has previously been described to bind mannosides. Here, we elucidated its ligand specificity by glycan array analysis, quantified the interaction with carbohydrates and validated high-mannose glycans as preferred ligands. Because the SARS-CoV-2 spike protein was previously reported to carry a high proportion of high-mannose N-glycans, we tested the binding of AcmJRL to recombinantly produced spike protein. We could demonstrate that AcmJRL binds the spike protein with a low micromolar KDin a carbohydrate-dependent fashion, suggesting its use as a potential SARS-CoV-2 neutralising agent.
Tumor-intrinsic PRC2 inactivation drives a context-dependent immune-desert tumor microenvironment and confers resistance to immunotherapy
Authors: Yan Juan , Chen Yuedan , Patel Amish J. , Warda Sarah , Nixon Briana G. , Wong Elissa W.P. , Miranda-Román Miguel A. , Lee Cindy J. , Yang Ning , Wang Yi , Sher Jessica , Giff Emily , Tang Fanying , Khurana Ekta , Singer Sam , Liu Yang , Galbo Phillip M. , Maag Jesper L. , Koche Richard P. , Zheng Deyou , Deng Liang , Antonescu Cristina R. , Li Ming , Chen Yu , Chi Ping 
Published: May 2022

AbstractImmune checkpoint blockade (ICB) has demonstrated clinical success in “inflamed” tumors with significant T-cell infiltrates, but tumors with an immune-desert tumor microenvironment (TME) fail to benefit. The tumor cell-intrinsic molecular mechanisms of the immune-desert phenotype remain poorly understood. Here, we demonstrate that inactivation of the Polycomb-repressive complex 2 (PRC2) core components, EED or SUZ12, a prevalent genetic event in malignant peripheral nerve sheath tumor (MPNST) and sporadically in other cancer types, drives a context-dependent immune-desert TME. PRC2 inactivation reprograms the chromatin landscape that leads to a cell-autonomous shift from primed baseline signaling-dependent cellular responses (e.g., interferon γ) to PRC2-regulated development and cellular differentiation transcriptional programs. Further, PRC2 inactivation reprograms the TME, leads to diminished tumor immune infiltrates and immune evasion through reduced chemokine production and impaired antigen presentation and T-cell priming, and confers ICB primary resistance through blunted T-cell recruitment in vivo. We demonstrate that strategies that enhancing innate immunity via intratumoral delivery of inactivated modified vaccinia virus Ankara (MVA) leads to increased tumor immune infiltrates and sensitizes PRC2-loss tumors to ICB. Our results provide novel molecular mechanisms of context-dependent dysfunctional epigenetic reprogramming that underline the immune-desert phenotype in MPNST and other cancers with PRC2 inactivation. Importantly, our findings highlight genetic-inactivation of PRC2 as a novel context-dependent ICB therapeutic resistance biomarker in cancer, and caution that therapeutic strategies that non-selectively target PRC2 in the host may lead to undesirable context-dependent immune evasion and ICB resistance in tumors. Our studies also point to intratumoral delivery of immunogenic therapeutic viruses as an initial strategy to modulate the immune-desert TME and capitalize on the clinical benefit of ICB.
Exploring Xylem Anatomical Adaptations Associated with Crassulacean Acid Metabolism and Hydraulic Capacitance in Clusia Leaves: Lessons for CAM Bioengineering
Authors: Leverett Alistair , Ferguson Kate , Winter Klaus , Borland Anne M. 
Published: May 2022

Abstract•Background and AimsMany succulent species are characterised by the presence of crassulacean acid metabolism (CAM) and/or elevated bulk hydraulic capacitance (CFT). Both CAM and elevated CFT substantially reduce the rate at which water moves through transpiring leaves. However, little is known about how these physiological adaptations are coordinated with leaf vascular architecture and xylem anatomy.•MethodsThe genus Clusia contains species spanning the entire C3-CAM continuum, and also is known to have > 5-fold interspecific variation in CFT. We used this highly diverse genus to explore how interspecific variation in vein density and xylem vessel dimensions are coordinated with CAM and CFT.•Key ResultsWe found that constitutive CAM phenotypes were associated with lower vein length per leaf area (VLA) and vein termini density (VTD), compared to C3 or facultative CAM species. However, when vein densities were standardised by leaf depth, this value was higher in CAM than C3 species, which is likely an adaptation to overcome apoplastic hydraulic resistance in deep chlorenchyma tissue. In contrast, CFT did not correlate with any xylem anatomical trait measured, suggesting CAM has a greater impact on leaf hydraulic physiology than CFT.•ConclusionsOur findings strongly suggest that CAM photosynthesis is coordinated with leaf vein densities. The link between CAM and vascular anatomy will be important to consider when attempting to bioengineer CAM into C3 crops.
PAF1 and FACT cooperate with MLL-AF4 to drive enhancer activity in leukemia
Authors: Crump Nicholas T. , Smith Alastair , Godfrey Laura , Jackson Nicole , Rice Siobhan , Kim Jaehoon , Basrur Venkatesha , Fermin Damian , Elenitoba-Johnson Kojo , Roeder Robert G. , Allis C. David , Roberts Irene , Roy Anindita , Milne Thomas A. 
Published: May 2022

SummaryAberrant enhancer activation has been identified as a key mechanism driving oncogene expression in many cancers. Here we use TOPmentation (Transcription factor-OPtimized ChIPmentation) to probe enhancer usage in primary MLL-rearranged acute lymphoblastic leukemia. We find that MLL-AF4, commonly held to promote transcription by binding to gene promoters, is also present at many active enhancers, where it assembles a complex of transcriptional co-activators normally found in the gene body. This includes DOT1L, ENL, PAF1, and a newly identified interaction with the histone chaperone FACT. By chemical degradation, we demonstrate that PAF1 and FACT are required for enhancer activity, including maintaining histone H3K27 acetylation, enhancer RNA transcription and enhancer-promoter interactions. This work identifies novel roles for PAF1 and FACT in enhancer function, and reveals an enhancer-targeting mechanism by which MLL-AF4 upregulates transcription, recruiting transcription machinery through a network of multivalent interactions to control enhancer activity and gene expression in acute leukemias.
New Vista into Origins of Viruses from a Prototypic ssDNA Phage
Authors: Kejzar Nejc , Laanto Elina , Rissanen Ilona , Abrishami Vahid , Selvaraj Muniyandi , Moineau Sylvain , Ravantti Janne , Sundberg Lotta-Riina , Huiskonen Juha T. 
Published: May 2022

AbstractViruses play a central role in all ecological niches; the origin of viruses, however, remains an open question. While phylogenetic analysis of distantly related viruses is hampered by a lack of detectable sequence similarity, structural biology can reveal conserved capsid protein structures that facilitate the study of distant evolutionary relationships. Here, we characterize the lipid-containing ssDNA temperate bacteriophage ΦCjT23, which is infecting Flavobacterium sp. (Bacteroidetes). We further detected ΦCjT23-like sequences in the genome of strains belonging to several Flavobacterium species. The virion structure determined by cryogenic electron microscopy revealed similarities to members of the viral kingdom Bamfordvirae that currently consists solely of dsDNA viruses. Common to these viruses, infecting hosts from all domains of life, is a major capsid protein composed of two upright β-sandwiches. The minimalistic structure of ΦCjT23 suggests that this phage serves as a model for the last common ancestor between ssDNA and dsDNA viruses in the Bamfordvirae. Both ΦCjT23 and the related phage FLiP infect Flavobacterium species found in several environments, suggesting that these types of viruses have a global distribution and shared evolutionary origin. Detailed comparisons to related, more complex viruses not only expand our knowledge about this group of viruses but also provide a rare glimpse into early virus evolution.
Bacterial capsular polysaccharides with antibiofilm activity share common biophysical and electrokinetic properties
Authors: Bayard-Bernal Joaquín , Thiebaud Jérôme , Brossaud Marina , Beaussart Audrey , Caillet Celine , Waldvogel Yves , Travier Laetitia , Létoffé Sylvie , Fontaine Thierry , Rokbi Bachra , Talaga Philippe , Beloin Christophe , Mistretta Noelle , Duval Jérôme F.L. , Ghigo Jean-Marc 
Published: May 2022

AbstractBacterial biofilms are surface-attached communities that are difficult to eradicate due to a high tolerance to antimicrobial agents. The use of non-biocidal surface-active compounds to prevent the initial adhesion and aggregation of bacterial pathogens is a promising alternative to antibiotic treatments and several antibiofilm compounds have been identified, including some capsular polysaccharides released by various bacteria. However, the lack of chemical and mechanistic understanding of the activity of these high-molecular-weight polymers limits their use for control of biofilm formation. Here, we screened a collection of 32 purified capsular polysaccharides and identified seven new compounds with non-biocidal activity against biofilms formed by Escherichia coli and/or Staphylococcus aureus. We analyzed the polysaccharide mobility under applied electric field conditions and showed that active and inactive polysaccharide polymers display distinct electrokinetic properties and that all active macromolecules shared high intrinsic viscosity features. Based on these characteristics, we identified two additional antibiofilm capsular polysaccharides with high density of electrostatic charges and their permeability to fluid flow. Our study therefore provides insights into key biophysical properties discriminating active from inactive polysaccharides. This characterization of a specific electrokinetic signature for polysaccharides displaying antibiofilm activity opens new perspectives to identify or engineer non-biocidal surface-active macromolecules to control biofilm formation in medical and industrial settings.Significance statementSome bacteria produce non-biocidal capsular polysaccharides that reduce the adhesion of bacterial pathogens to surfaces. Due to a lack of molecular and structural definition, the basis of their antiadhesion activity is unknown, thus hindering their prophylactic use for biofilm control. Here, we identified nine new active compounds and compared their composition, structure and biophysical properties with other inactive capsular polysaccharides. Despite the absence of specific molecular motif, we demonstrate that all active polysaccharides share common electrokinetic properties that distinguish them from inactive polymers. This characterization of the biophysical properties of antibiofilm bacterial polysaccharide provides key insights to engineer non-biocidal and bio-inspired surface-active compounds to control bacterial adhesion in medical and industrial settings.