bluuebunny/crossref_metadata_2025_split huggingface dataset:
Re-examining the meningitis belt: associations between environmental factors and epidemic meningitis risk across Africa
Authors: Cliff Molly , Jahn Sally , Fouda Andre Bita , Latt Anderson , Lingani Clement , Trotter Caroline 
Published: February 2025

AbstractIn 2002 Molesworth et al created a logistic regression model to investigate the spatial distribution of meningitis epidemics in Africa and determine geographical risk. We aim to understand if the meningitis belt geography and environmental risk factors have changed in the last 20 years by updating this analysis. Epidemic bacterial meningitis data from 2003-2022 were provided by WHO-AFRO. Districts (ADMN2) across Africa were coded as 1 if they had experienced a meningitis outbreak and 0 if they hadn’t. Environmental data were obtained from open sources. To preserve seasonal climate variation, monthly means of wind speed, rainfall, dust, and humidity were processed into climatic profiles using k-means clustering. Logistic regression was carried out with meningitis epidemic history as the dependent variable and k-means clusters of rainfall, dust, humidity, and windspeed, alongside average land-cover type as the independent variables. A sensitivity analysis was conducted excluding the Democratic Republic of Congo (DRC), due to limited laboratory confirmation of suspected cases. Rainfall, dust, and humidity demonstrated the strongest statistical association with meningitis outbreaks and were included in our final model. With a probability cutoff value of >0.4, our model had a specificity and sensitivity of 81.0% and 84.3% respectively in identifying districts having experienced a meningitis epidemic. With an extended dry season, the Sahelian region had the highest risk of meningitis outbreaks (probability >0.8). The inclusion/exclusion of the DRC had a significant impact on our model. Whilst Republic of the Congo, Gabon, Liberia, and Angola had a moderate risk of meningitis (probability >0.4) within our full model, no countries surrounding the meningitis belt were at risk for outbreaks within the sensitivity analysis. Although our research may suggest a south-westerly expansion of the meningitis belt this is difficult to verify. Surveillance of suspected meningitis cases should be accompanied by laboratory confirmation to improve outbreak definition.
CD4 T cell counts are inversely correlated with anti-cluster A antibodies in antiretroviral therapy-treated PLWH
Authors: Benlarbi Mehdi , Richard Jonathan , Clemente Tommaso , Bourassa Catherine , Tolbert William D. , Gottumukkala Suneetha , Peet Marc-Messier , Medjahed Halima , Pazgier Marzena , Maldarelli Frank , Castagna Antonella , Durand Madeleine , Finzi Andrés 
Published: February 2025

SummaryWhile antiretroviral therapy efficiently suppresses viral replication, inflammation and immune dysfunction persist in some people living with HIV-1 (PLWH). Soluble gp120 (sgp120) has been detected in PLWH plasma and its presence is linked to immune dysfunction. It was reported that sgp120 binding to CD4 on uninfected bystander CD4+T cells sensitizes them to antibody-dependent cellular-cytotoxicity (ADCC) mediated by non-neutralizing antibodies present in PLWH plasma. Using three independent PLWH cohorts, we observed that non-neutralizing anti-cluster A antibodies are negatively associated with CD4+T cell counts. Anti-CD4BS antibodies blocked the coating of uninfected bystander cells by sgp120, thereby preventing their elimination by ADCC. Supporting a protective role of anti-CD4BS antibodies, PLWH having these antibodies didn’t show a negative association between CD4 T cell counts and anti-cluster A. Our results reveal that anti-cluster A antibodies are associated with immune dysfunction in PLWH and anti-CD4BS antibodies might have a beneficial impact in these individuals.
Graft-versus-host disease prophylaxis shapes T cell biology and immune reconstitution after hematopoietic cell transplant
Authors: Siegel Steven J. , DeWolf Susan , Schmalz Joseph , Saber Wael , Dong Jiayi , Martens Michael J. , Logan Brent , Albanese Alexandre , Iovino Lorenzo , Chen Edward , Kaminski James , Neuberg Donna , Hebert Kyle , Keskula Paula , Zavistaski Jillian , Steinberg Lea , Schichter Isabella , Cagnin Lorenzo , Hernandez Vanessa , Warren Makya , Applegate Kristy , Bar Merav , Chhabra Saurabh , Choi Sung Won , Clark William , Das Suman , Jenq Robert , Jones Richard J. , Levine John E. , Murthy Hemant , Rashidi Armin , Riches Marcie , Sandhu Karamjeet , Sung Anthony D. , Larkin Karilyn , Al Malki Monzr M. , Gooptu Mahasweta , Elmariah Hany , Alousi Amin , Runaas Lyndsey , Shaffer Brian , Rezvani Andrew , Jurdi Najla El , Loren Alison W. , Scheffey Danielle , Sanders Catherine , Hamadani Mehdi , Dudakov Jarrod , Bien Stephanie , Robins Harlan , Horowitz Mary , Bolaños-Meade Javier , Holtan Shernan , Bhatt Ami S. , Perales Miguel-Angel , Kean Leslie S. 
Published: February 2025

AbstractSuccessful hematopoietic cell transplant requires immunosuppression to prevent graft-versus-host disease (GVHD), a lethal, T-cell-mediated post-transplant complication. The phase 3 BMT CTN 1703 trial demonstrated superior GVHD-free/relapse-free survival for post-transplant cyclophosphamide (PT-Cy)-based GVHD prophylaxis versus tacrolimus/methotrexate (Tac/MTX), but did not improve overall survival. To compare T-cell biology between GVHD prophylaxis regimens, 324 patients were co-enrolled onto BMT CTN 1801 (NCT03959241). We quantified T-cell immune reconstitution using multi-modal analysis, including T-cell receptor (TCR) sequencing of 2,359 longitudinal samples (180,432,350 T-cells). Compared to Tac/MTX, PT-Cy was associated with an early, substantial reduction in TCR diversity that was sustained for 2 years. PT-Cy led to a T-cell reconstitution bottleneck, including reduced thymic output and virus-associated TCRs. Decreased D+14 TCR diversity predicted prevention of chronic GVHD, but also correlated with increased moderate-to-severe infections. This study reveals how distinct immunosuppression strategies have significant effects on the global immune repertoire, underpinning post-transplant clinical outcomes.
Gaps in integration of sexual and reproductive health and rights into climate change research in sub-Saharan Africa: A scoping review
Authors: Amadi Jacinter A. , Odwe George , Onyango Francis O. , Kangwana Beth 
Published: February 2025

AbstractSub-Saharan Africa is faced with triple challenges of high vulnerability to climate change (CC) impacts, high levels of inequality and poor sexual and reproductive health and rights (SRHR) outcomes. Climate change can worsen SRHR situation for high-risk groups such as women, children, adolescent girls and people living with HIV. This scoping review takes stock of the state of research on the intersection between CC and SRHR in SSA with a view of identifying gaps and opportunities for effective evidence generation and integration in climate actions. The review followed Arksey and O’Malley framework. Data charting was conducted using Population, Exposure, Comparator, Outcome tool in Covidence. Thirty-seven (37) studies were reviewed, 57% were quantitative while 41% and 2% used qualitative and mixed methods respectively. SRHR components investigated include maternal newborn and child health at 43% (n=16), HIV at 19% (n=7), gender-based violence at 11% (n=4), and fertility intentions and outcomes at 11% (n=4). SRHR elements that are under-researched in the context of CC include access to and uptake of contraceptives, post abortion care, harmful practices (child marriages and female genital mutilation), menstrual health, pregnancy losses, bodily autonomy, and (in)fertility. Drought, floods, heat stress and rainfall seasonality have received fair attention in research, yet impacts of climate hazards like tropical cyclones, wildfires and salt-water intrusion are missing in research. There is inadequate research at the intersection of CC and SRHR hindering progress towards climate resilience and attainment of good health and well-being for all. Effective and equitable integration requires that SRHR issues be recognized, and deliberate investments (research, policies, programs, interventions and financing) put in place to address the critical SRHR gaps and climate vulnerabilities to enhance resilience.
Age-Dependent Sex Disparities in Sjogren’s Disease Prevalence Align with Natural Hormone Fluctuations
Authors: Diggins Eliza C. , Weller Melodie L. 
Published: February 2025

AbstractSjogren’s Disease (SjD), like many autoimmune diseases, shows a strong female-to-male sex bias, raising the possibility of a hormone-mediated mechanism. However, specific hormonal drivers and the underlying mechanisms remain unclear. In this study, we analyze a electronic health record dataset containing >100,000 SjD patients, allowing for a comprehensive statistical investigation into sex bias and serum hormone levels associated with SjD susceptibility. Focusing on testosterone, estradiol, and sex hormone-binding globulin (SHBG), our analysis reveals an age-dependent trend in SjD’s sex bias, with a substantially reduced female bias observed in pediatric cases. This finding, alongside statistical modeling, suggests that testosterone or estradiol may influence the sex disparity in SjD prevalence, with distinct effects at different life stages. Specifically, we observe a higher percentage of male SjD patients in early childhood (30.06%, [CI: 26.16-34.11]), declining sharply in late pubescence into adulthood (9.85% [CI: 9.51–10.16]), followed by a secondary steady increase in male prevalence among older adults (13.50% [CI: 13.25-13.76]). Our models indicate that these shifts in sex bias align with typical age-related hormonal changes rather than abnormal levels, suggesting that natural hormone fluctuations may play a significant role in modulating disease susceptibility. This research not only refines our understanding of SjD but also underscores the importance of hormone-level monitoring in future SjD studies and potential therapeutic strategies. Advanced studies are required to further clarify whether testosterone or estradiol is the primary mediator of these trends, promising new insights into hormone-linked pathways and autoimmune disease pathogenesis.
Physicians’ Knowledge and Experiences of Counseling on Complementary, Alternative, and Integrative Medicine in Cancer Care: A Qualitative Systematic Review
Authors: Ng Jeremy Y. , Shah Aimun Qadeer , Narr Lana Abu , Qian Alyssa , Cramer Holger 
Published: February 2025

AbstractBackgroundDespite the increasing use of complementary, alternative, and integrative medicine (CAIM) use among cancer patients, there remains ambiguity surrounding physicians’ understanding and counseling practices in this area. The objective of this qualitative systematic review was to identify the knowledge and experiences of physicians who counsel patients on CAIM in the context of cancer.MethodsMEDLINE, EMBASE, and AMED were systematically searched from inception to May 27, 2023. Reference lists of relevant review articles were also hand- searched. Eligible articles contained qualitative data focused on physicians’ perceived knowledge and experience pertaining to CAIM counseling for cancer care. Relevant findings were extracted and analyzed using a narrative synthesis approach to identify key themes and subthemes.ResultsThirty-five articles were included (30 from database searching and 5 from hand-searching reference lists). Four main themes were identified: lack of knowledge and formal training on CAIM; distrust and concern about CAIM safety and/or efficacy; accepting CAIM as an important part of cancer care; and the communication dynamics between patients and physicians.ConclusionsThis study highlights that physicians recognize CAIM as an important component of person-centered and holistic cancer care; however, they have concerns about the safety and/or efficacy of these therapies. Accordingly, there is a need for improved education for physicians on the safety and effectiveness of CAIMs, to better equip them to effectively counsel patients in this area. Future research exploring the perspectives of medical trainees and other healthcare providers on CAIM for cancer is also warranted.
The Critical Role of the 2’-OH group in Phase Separation and Percolation Transitions of RNA
Authors: Wadsworth Gable M. , Aierken Dilimulati , Thurston George M. , Joseph Jerelle A. , Banerjee Priya R. 
Published: February 2025

AbstractMg2+ion-dependent RNA liquid–liquid phase separation with lower critical solution temperatures is driven by the phosphate backbone and modulated by the solvation property of nucleobases. Here, we report a key role of the 2’-OH group of ribose sugar in RNA condensation in the presence of divalent cations. We show that 2’-deoxyribose inhibits nucleic acid phase separation and suppresses the intra-condensate networking transition, known as percolation, that underlies the condensate dynamical arrest. All-atom simulations reveal increased solvation and compaction of single-stranded DNA compared to RNA, suggesting an unintuitive role of chain flexibility in modulating heat-induced nucleic acid phase separation and percolation transitions. Further, 2’-O-methylation (2’-O-Me) of RNA, a common sugar modification, lowers the driving force of RNA phase transitions. These results highlight the diverse physicochemical parameters governing nucleic acid phase behavior and suggest how sugar modifications may have evolved to robustly tune the formation and dynamical arrest of RNA condensates.
TNF signaling maintains local restriction of bacterial founder populations in intestinal and systemic sites during oralYersiniainfection
Authors: Peterson Stefan T. , Dailey Katherine G. , Hullahalli Karthik , Sorobetea Daniel , Matsuda Rina , Sewell Jaydeen , Yost Winslow , O’Neill Rosemary , Bobba Suhas , Apenes Nicolai , Sherman Matthew E. , Balazs George I. , Assenmacher Charles-Antoine , Cox Arin , Lanza Matthew , Shin Sunny , Waldor Matthew K. , Brodsky Igor E. 
Published: February 2025

AbstractEnteroinvasive bacterial pathogens are responsible for an enormous worldwide disease burden that critically affects the young and immunocompromised.Yersinia pseudotuberculosisis a Gram-negative enteric pathogen, closely related to the plague agentY. pestis,that colonizes intestinal tissues, induces the formation of pyogranulomas along the intestinal tract, and disseminates to systemic organs following oral infection of experimental rodents. Prior studies proposed that systemic tissues were colonized by a pool of intestinal replicating bacteria distinct from populations within Peyer’s patches and mesenteric lymph nodes. Whether bacteria within intestinal pyogranulomas serve as the source for systemic dissemination, and the relationship between bacterial populations within different tissue sites is poorly defined. Moreover, the factors that regulateYersiniacolonization and dissemination are not well understood. Here, we demonstrate, using Sequence Tag-based Analysis of Microbial Populations in R (STAMPR), that remarkably small founder populations independently colonize intestinal and systemic tissues. Notably, intestinal pyogranulomas contain clonal populations of bacteria that are restricted and do not spread to other tissues. However, populations ofYersiniaare shared among systemic organs and the blood, suggesting that systemic dissemination occurs via hematogenous spread. Finally, we demonstrate that TNF signaling is a key contributor to the bottlenecks limiting both tissue colonization and lymphatic dissemination of intestinal bacterial populations. Altogether, this study reveals previously undescribed aspects of infection dynamics of enteric bacterial pathogens.ImportanceBacterial escape from the intestine can lead to severe disease, including sepsis, organ damage, and death. However, the intestinal bacterial population dynamics governing the colonization of mucosal and systemic tissues and the intestinal sites that seed systemic spread are not clear.Yersinia pseudotuberculosisis a rodent and human intestinal pathogen closely related to the plague agent and provides a natural rodent-adapted model to study systemic bacterial dissemination. Our findings define the infection dynamics of entericYersiniaand the impact of the innate immune system onYersiniacolonization of the intestine and systemic organs.
Mapping the genetic landscape of iron metabolism uncovers the SETD2 methyltransferase as a modulator of iron flux
Authors: Martinelli Anthony W. , Wu Chun-Pei , Vornbäumen Tristan , Wit Niek , Sia Jia J. , Speak Anneliese O. , Nathan James A. 
Published: February 2025

AbstractCellular iron levels must be tightly regulated to ensure sufficient iron for essential enzymatic functions whilst avoiding the harmful generation of toxic species. Here, to better understand how iron levels are controlled, we carry out genome-wide mutagenesis screens in human cells. Alongside mapping known components of iron-sensing, we determine the relative contributions of iron uptake, iron recycling, ferritin breakdown, and mitochondrial flux in controlling the labile iron pool. We also identify SETD2, a histone methyltransferase, as a chromatin modifying enzyme that controls intracellular iron availability through ferritin breakdown. Functionally, we show that SETD2 inhibition or cancer-associated SETD2 mutations render cells iron deficient, thereby driving resistance to ferroptosis, and potentially explaining how some tumours evade anti-tumoural immunity.
Inhibitory and disinhibitory VIP IN-mediated circuits in neocortex
Authors: Dellal Shlomo , Zurita Hector , Valero Manuel , Abad-Perez Pablo , Kruglikov Ilya , Meng John , Prönneke Alvar , Hanson Jessica L. , Mir Ema , On-garo Marina , Wang Xiao-Jing , Buzsáki György , Machold Robert , Rudy Bernardo 
Published: February 2025

AbstractCortical GABAergic interneurons (INs) are comprised of distinct types that provide tailored inhibition to pyramidal cells (PCs) and other INs, thereby enabling precise control of cortical circuit activity. INs expressing the neuropeptide vasoactive-intestinal peptide (VIP) have attracted attention recently following the discovery that they predominantly function by inhibiting dendritic-targeting somatostatin (SST) expressing INs, thereby disinhibiting PCs. This VIP-SST disinhibitory circuit motif is observed throughout the neocortex from mice to humans, and serves as a key mechanism for top-down (feedback) and context-dependent information processing. Thus, VIP IN-mediated disinhibition has been found to play an important role in sensory processing, control of executive functions, attention, sensorimotor integration and other cortico-cortical and thalamocortical feedback interactions. Furthermore, VIP INs have been implicated in mediating the effects of reinforcement signals, both reward and aversive, via their responsiveness to neuromodulators such as acetylcholine (ACh), and in facilitating synaptic plasticity and learning. While it is evident from transcriptomic analyses that VIP INs are a molecularly heterogeneous group, the physiological significance of this diversity is unclear at present. Here, we have characterized the functional diversity of VIP INs in the primary somatosensory cortex by leveraging intersectional genetic approaches to study distinct VIP IN subtypes. We found that VIP INs can be divided into four different populations: a group that expresses the Ca2+-binding protein calretinin (CR), two distinct groups that express the neuropeptide cholecystokinin (CCK), and a group that does not express either CR or CCK (non-CCK non-CR; or nCCK nCR). VIP neurons in each group exhibit different laminar distributions, axonal and dendritic arbors, intrinsic electrophysiological properties, and efferent connectivity, VIP/CR INs target almost exclusively SST INs, VIP/nCCK nCR INs also mainly target SST INs but also have connections to parvalbumin (PV) expressing INs. These two groups have essentially no connectivity to pyramidal cells (PCs). On the other hand, the two types of VIP/CCK INs target PCs, but differ in the degree to which synaptic release from each type is modulated by endocannabinoids. We also found that long-range inputs differentially recruit distinct VIP IN groups. Intriguingly, we find that distinct VIP IN populations target distinct SST INs subtypes in turn, indicating the presence of specialized VIP-SST disinhibitory subcircuits. Activation of distinct VIP IN subpopulationsin vivoresults in differential effects on the cortical network, thus providing evidence for modularity in VIP IN-mediated actions during cortical information processing.
Nuclear speckle proteins form intrinsic andMALAT1-dependent microphases
Authors: Shinn Min Kyung , Tomares Dylan T. , Liu Vicky , Pant Avnika , Qiu Yuanxin , Song You Jin , Ayala Yuna , Strout Gregory W. , Ruff Kiersten M. , Lew Matthew D. , Prasanth Kannanganattu V. , Pappu Rohit V. 
Published: February 2025

SummaryNuclear speckles are enriched in serine / arginine rich splicing factors (SRSFs), such as SRSF1. Splicing factors and proteins such as TDP-43 concentrate into distinct speckle territories to enable pre-mRNA processing. We have discovered that SRSFs and TDP-43 are block copolymers and the protein-specific interplay of inter-block repulsions and attractions drives spontaneous microphase separation. This gives rise to size-limited, ordered assemblies, that are 30 – 45 nm in diameter. Depending on the protein, each microphase comprises several tens to hundreds of molecules. The sub-micron scale territories observed in cells are shown to be clusters of microphases. The regulatory lncRNAMALAT1binds preferentially to SRSF1 microphases to enhance microphase separation and alter microphase structures. Microphase separation enables the concentration of finite numbers of splicing factors into assemblies with distinct nanoscale structures that can be modulated byMALAT1. Our findings provide a structural framework for the functional organization of splicing factors.
Risk-reward trade-off in motility endurance generates dichotomy in search strategies among copiotrophic marine bacteria
Authors: Keegstra Johannes M. , Landry Zachary C. , Zweifel Sophie T. , Roller Benjamin R.K. , Martínez-Pérez Clara , Clerc Estelle E. , Ackermann Martin , Stocker Roman 
Published: February 2025

AbstractCoptiotrophic marine bacteria contribute significantly to carbon storage in the ocean by remineralizing organic carbon present in nutrient-rich hotspots amidst oligotrophic waters. Motility is both highly beneficial and costly in such environments, presenting copiotrophs with a risk–reward trade-off in search behavior. Here we studied the motility endurance of 26 marine isolates using video microscopy and cell tracking over two days of carbon starvation. We found that this cost-benefit trade-off results in a distinct dichotomy among marine bacteria: risk-averse copiotrophs ceased motility within hours (‘limostatic’), whereas risk-prone copiotrophs converted 10% of their biomass per day into energy to retain motility for the two days of observation (‘limokinetic’). We identified a genomic component of this dichotomy, sufficiently robust to predict the response of additional species with 83% accuracy and the prevalence of both strategies in the ocean. This dichotomy can facilitate the incorporation of the bacterial contribution in ocean carbon cycle models.