bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence, clusters, and burden of complex tuberculosis multimorbidity in low- and middle-income countries: a systematic review and meta-analysis
Authors: Jarde Alexander , Ma Ruimin , Todowede Olamide O. , Latif Abdul , Yaqoob Aashifa , Afaq Saima , Ferdous Tarana , Tomeny Ewan M , Rosu Laura , Mrema Lucy Elauteri , Rakhshanda Shagoofa , Fazid Sheraz , Rahman Farah Naz , Egere Uzochukwu , Elsony Asma , Elsey Helen , Siddiqi Kamran , Stubbs Brendon , Siddiqi Najma 
Published: September 2022

AbstractObjectivesThe co-occurrence of tuberculosis (TB) and multiple chronic communicable and non-communicable diseases is a growing concern in low- and middle-income countries (LMICs). Understanding this ‘complex TB multimorbidity’ (cTBMM) can contribute to improved patient care. We aimed to synthesise the prevalence of clusters of cTBMM and their impact on patient outcomes.DesignSystematic review and meta-analysis.SettingLMICs.PapersWe searched major databases from inception to 01/10/2020 to identify observational studies reporting primary (prevalence or risk) or secondary (related to disease burden) outcome data for people in LMICs with cTBMM. Titles, abstracts and full text screening, data extraction, and quality assessment were done in duplicate by independent reviewers, and random-effects meta-analyses were performed.Primary and secondary outcome measuresPrevalence or risk of cTBMM (primary); any measure of burden of disease (secondary).ResultsFrom 21,884 search results, 82 studies representing 773,828 TB patients were included, reporting data on 78 different clusters of cTBMM. In TB patients, the most prevalent co-occurring conditions where depression and anxiety (15.3%, 95% confidence interval [CI] 10.7%-20.5%, 3 studies, 1,473 participants, I2=64%), HIV and anxiety (15.2%, 95%CI 11.3%-19.7%, 4 studies, 1,413 participants, I2=77%), and HIV and post-traumatic stress disorder (14.8%, 95%CI 13.9%-15.8%, 2 studies, 5,400 participants). Sparse evidence indicated lower treatment success and higher risks of death in people with cTBMM.ConclusionsAlthough limited by high heterogeneity, this first systematic review and meta-analysis on cTBMM highlights that multiple conditions co-occurring in TB patients are common and that mental disorders often cluster together or with HIV. Further research assessing the burden of cTBMM and identifying effective health systems responses is required.RegistrationProspero CRD42020214021.Strengths and limitations of this studyTo our knowledge, this is the first systematic review summarising the prevalence of the different clusters of complex TB multimorbidity (cTBMM) in LMICs.While our focus was on cTBMM in LMICs overall, subgroup analyses by type of TB, country, and socio-economic group allow for a more nuanced assessment on cTBMM.We used a broad definition for the term ‘chronic condition’ to be as inclusive as possible, but which could lead to heterogeneity in the definition of some clusters of cTBMM.
Infliximab for Treatment of Adults Hospitalized with Moderate or Severe Covid-19
Authors: O’Halloran Jane A. , Kedar Eyal , Anstrom Kevin J. , McCarthy Matthew W. , Ko Emily R. , Nunez Patricia Segura , Boucher Cynthia , Smith P. Brian , Panettieri Reynold A. , de Tai Sabina Mendivil Tuchia , Maillo Martin , Khan Akram , Mena Lora Alfredo J. , Salathe Matthias , Capo Gerardo , Gonzalez Daniel Rodríguez , Patterson Thomas F , Palma Christopher , Ariza Horacio , Lima Maria Patelli , Lachiewicz Anne M. , Blamoun John , Nannini Esteban C. , Sprinz Eduardo , Mykietiuk Analia , Alicic Radica , Rauseo Adriana M. , Wolfe Cameron R. , Witting Britta , Benjamin Daniel K. , McNulty Steven E. , Zakroysky Pearl , Halabi Susan , Butler Sandra , Atkinson Jane , Adam Stacey J. , Melsheimer Richard , Chang Soju , LaVange Lisa , Proschan Michael , Bozzette Samuel A. , Powderly William G. ,   ACTIV-1 IM study group members
Published: September 2022

ABSTRACTBackgroundImmune dysregulation contributes to poorer outcomes in severe Covid-19. Immunomodulators targeting various pathways have improved outcomes. We investigated whether infliximab provides benefit over standard of care.MethodsWe conducted a master protocol investigating immunomodulators for potential benefit in treatment of participants hospitalized with Covid-19 pneumonia. We report results for infliximab (single dose infusion) versus shared placebo both with standard of care. Primary outcome was time to recovery by day 29 (28 days after randomization). Key secondary endpoints included 14-day clinical status and 28-day mortality.ResultsA total of 1033 participants received study drug (517 infliximab, 516 placebo). Mean age was 54.8 years, 60.3% were male, 48.6% Hispanic or Latino, and 14% Black. No statistically significant difference in the primary endpoint was seen with infliximab compared with placebo (recovery rate ratio 1.13, 95% CI 0.99–1.29; p=0.063). Median (IQR) time to recovery was 8 days (7, 9) for infliximab and 9 days (8, 10) for placebo. Participants assigned to infliximab were more likely to have an improved clinical status at day 14 (OR 1.32, 95% CI 1.05–1.66). Twenty-eight-day mortality was 10.1% with infliximab versus 14.5% with placebo, with 41% lower odds of dying in those receiving infliximab (OR 0.59, 95% CI 0.39–0.90). No differences in risk of serious adverse events including secondary infections.ConclusionsInfliximab did not demonstrate statistically significant improvement in time to recovery. It was associated with improved 14-day clinical status and substantial reduction in 28- day mortality compared with standard of care.Trial registrationClinicalTrials.gov (NCT04593940).
Identification of Causal Pathways among Gut Microbiota, Food Intake and Telomere Length: A Mendelian Randomization Study
Authors: Hou Lei , Yu Yuanyuan , Jin Chuandi , Zhang Lei , Ge Yilei , Liu Xinhui , Wu Sijia , Qian Fengtong , Wu Yutong , Yu Yifan , Luo Qingxin , He Yina , Feng Yue , Wei Yun , Li Hongkai , Xue Fuzhong 
Published: September 2022

AbstractBackgroundDietary habit plays an important role in the composition and function of gut microbiota which possibly manipulates host eating behavior. Gut microflora and nutritional imbalance are associated with telomere length (TL). However, the causality among them remains unclear.MethodsFirstly, we calculate the significance threshold based on genetic correlations. Then we perform bi-directional Mendelian Randomization (MR) analyses among 82 food intakes (FIs) (UK Biobank, N=455,146), 95 gut microbial traits (Flemish Gut Flora Project, N=2,223) and TL (genome-wide meta-analysis from 15 cohorts, N=37,684) using summary-level data from large genome-wide association studies. Fixed-effect inverse variance weighting is the main analysis method and the other eight two-sample MR methods and three sensitivity analyses are performed. Finally, GO enrichment analyses are used to investigate the bio-function.ResultsSeveral bi-directional causal relationships among gut microbiota, FIs and TL are obtained by two-sample MR. Overall, we find suggestive evidence of three main causal pathways among them. Drinking more glasses of water per day is able to affect the habit of eating dried fruit through the host gut microbiota (Barnesiella). The change of one gut microbiota taxon (Collinsella) in the host causally influences another gut microbiota taxon (Lactonccus) through the diet habits (intake of oil-based spread). Additionally, the TL alters the habits of drinking ground coffee and further affects the gut microbiota (Acidaminococcaceae). GO enrichment analysis further confirmed the MR results.ConclusionTL has an impact on diet habits and gut microbiota and there are bi-directional relationships between diet habits and gut microbiota.
A Haptoglobin (HP) Structural Variant Alters the Effect of APOE Alleles on Alzheimer’s Disease
Authors: Bai Haimeng , Naj Adam C. , Benchek Penelope , Dumitrescu Logan , Hohman Timothy , Hamilton-Nelson Kara , Kallianpur Asha R. , Griswold Anthony J. , Vardarajan Badri , Martin Eden R. , Beecham Gary W. , Below Jennifer E. , Schellenberg Gerard , Mayeux Richard , Farrer Lindsay , Pericak-Vance Margaret A. , Haines Jonathan L. , Bush William S. ,   Alzheimer’s Disease Genetics Consortium
Published: September 2022

AbstractBackgroundHaptoglobin (HP) is an antioxidant of apolipoprotein E (APOE), and previous reports have shown HP binds with APOE and amyloid-β (Aβ) to aid its clearance. A common structural variant of the HP gene distinguishes it into two alleles: HP1 and HP2.MethodsHP genotypes were imputed in 29 cohorts from the Alzheimer’s Disease (AD) Genetics Consortium (N=22,651). Associations between the HP polymorphism and AD risk and age of onset through APOE interactions were investigated using regression models.ResultsThe HP polymorphism significantly impacts AD risk and age at onset in European-descent individuals (and in meta-analysis with African Americans) by modifying both the protective effect of APOEε2 and the detrimental effect of APOEε4, especially for APOEε4 carriers.DiscussionThe effect modification of APOE by HP suggests adjustment and/or stratification by HP genotype is warranted when APOE risk is considered. Our findings also provided directions for further investigations on potential mechanisms behind this association.
Grazers affect the composition of dissolved storage glycans and thereby bacterioplankton composition during a biphasic North Sea spring algae bloom
Authors: Sidhu Chandni , Kirstein Inga V. , Meunier Cédric L. , Rick Johannes , Wiltshire Karen H. , Steinke Nicola , Vidal-Melgosa Silvia , Hehemann Jan-Hendrik , Huettel Bruno , Schweder Thomas , Fuchs Bernhard M. , Amann Rudolf I. , Teeling Hanno 
Published: September 2022

AbstractBlooms of marine microalgae play a pivotal role in global carbon cycling. Such blooms entail successive blooms of specialized clades of planktonic bacteria that remineralize algal biomass. We investigated the bacterioplankton response to a bloom in the German Bight in spring 2020. Metagenome sequencing at 30 time-points allowed reconstruction of 251 metagenome-assembled genomes (MAGs), 245 representing as yet uncultured species, while corresponding metatranscriptome sequencing highlighted 50 particularly active MAGs. Together with algae, copepod, protist and bacteria diversity and abundance data in combination with physico-chemical data and antibody-based saccharide measurements, we demonstrate (i) how dissolved primary photoassimilated algal and secondary bacterial storage glycans shape the bacterioplankton community composition, and (ii) how grazing on higher trophic levels determines the release of these abundant glycans. We thus elucidate principles governing how bacterioplankton clades respond to algal blooms and collectively remineralize gigatons of carbon annually on a global scale.
SIMBSIG: Similarity search and clustering for biobank-scale data
Authors: Adamer Michael F. , Roellin Eljas , Bourguignon Lucie , Borgwardt Karsten 
Published: September 2022

AbstractSummaryIn many modern bioinformatics applications, such as statistical genetics, or single-cell analysis, one frequently encounters datasets which are orders of magnitude too large for conventional in-memory analysis. To tackle this challenge, we introduce SIMBSIG, a highly scalable Python package which provides a scikit-learn-like interface for out-of-core, GPU-enabled similarity searches, principal component analysis, and clustering. Due to the PyTorch backend it is highly modular and particularly tailored to many data types with a particular focus on biobank data analysis.AvailabilitySIMBSIG is freely available from PyPI and its source code and documentation can be found on GitHub (https://github.com/BorgwardtLab/simbsig) under a BSD-3 license.Contactmichael.adamer@bsse.ethz.ch
An optimized workflow to generate and characterize iPSC-derived motor neuron (MN) spheroids
Authors: Castellanos-Montiel Maria Jose , Chaineau Mathilde , Franco-Flores Anna Kristyna , Haghi Ghazal , Carrillo-Valenzuela Dulce , Reintsch Wolfgang E. , Chen Carol X-Q , Durcan Thomas M. 
Published: September 2022

AbstractMotor neuron diseases (MNDs) are characterized by the progressive degeneration of motor neurons (MNs) from the cortex, brainstem and/or the spinal cord. In an effort to understand the underlying causes of this selective degeneration, a multitude ofin vitromodels based on induced pluripotent stem cell (iPSC)-derived MNs have been developed. Moreover, different groups have started to use advanced 3D structures, composed of MNs and other cell types to increase the physiological relevance of suchin vitromodels. For instance, spheroids are simple 3D models that have the potential to be generated in large numbers that can be used across different assays. In this study, we generated MN spheroids and developed a workflow to analyze them. We confirmed the expression of different MN markers as the MN spheroids differentiate, at both the transcript and protein level, as well as their capacity to display functional activity in the form of action potentials (APs) and bursts. We also identified the presence of other cell types, namely interneurons and oligodendrocytes, which share the same neural progenitor pool with MNs. In summary, we successfully developed a MN 3D model, and we optimized a workflow that can be applied to their characterization and analysis. In the future, we will apply this model and workflow to the study of MNDs by generating MN spheroids from patient-derived iPSC lines, aiming to contribute to the development of more advance and physiologicalin vitrodisease models.
A novel sperm-derived seminal fluid protein inCaenorhabditisnematodes
Authors: Kasimatis Katja R. , Rehaluk Christine , Rowe Locke , Cutter Asher D. 
Published: September 2022

ABSTRACTNematode sperm contain subcellular vesicles known as membranous organelles (MOs) that fuse with the cell membrane upon sperm activation to release their soluble contents into the extracellular space. The second most abundant proteins in the MOs belong to the conserved Nematode-Specific Peptide family, group F (NSPF) gene family. We hypothesize that these proteins contribute to seminal fluid and are part of post-insemination reproductive tract dynamics. We characterized the anatomical region where the NSPF proteins likely function during fertilization using whole-worm immunostaining of a His-taggednspf-1transgene. We confirmed that NSPF proteins are transferred to females during mating. NSPF proteins localize to the uterus lumen when transferred to mated females and in unmated adult hermaphrodites. These results suggest that the uterine localization of the NSPF proteins is likely a functional property of both male-derived sperm and self-sperm and not incidental to the point of transfer during mating. In males, we found that NSPF presence and abundance was correlated with reproductive maturity. We then used experimental evolution to compete the wildtype allele against a deletion allele in 10 replicate obligate-outcrossing populations. We calculated a mean selective disadvantage of 0.1% for the deletion allele, which indicated that the NSPF genes are beneficial to male fitness. This conclusion was reinforced by qualitative trends from lower powered single-generation fertility assays. Together we demonstrate that nematodes use a novel mechanism for generating seminal fluid proteins and show that the highly abundant NSPF proteins likely have a beneficial impact on fitness.
Diversification is correlated with temperature in white and sulfur butterflies
Authors: Carvalho Ana Paula S. , Owens Hannah L. , Laurent Ryan A. St , Earl Chandra , Dexter Kelly M. , Messcher Rebeccah L. , Willmott Keith R. , Aduse-Poku Kwaku , Collins Steve C. , Homziak Nicholas T. , Hoshizaki Sugihiko , Hsu Yu-Feng , Kizhakke Athulya G. , Kunte Krushnamegh , Martins Dino J. , Mega Nicolás O. , Morinaka Sadaharu , Peggie Djunijanti , Romanowski Helena P. , Sáfián Szabolcs , Vila Roger , Wang Houshuai , Braby Michael F. , Espeland Marianne , Breinholt Jesse W. , Pierce Naomi E. , Kawahara Akito Y. , Lohman David J. 
Published: September 2022

AbstractTemperature is thought to be a key variable explaining global patterns of species richness. However, to investigate this relationship carefully, it is necessary to study clades with broad geographic ranges that are comprised of species inhabiting diverse biomes with well- characterized species ranges. In the present study, we investigate the link between temperature and diversification in the butterfly family Pieridae (sulfurs and whites) by combining Next Generation sequences and published molecular data with fine-grained distribution information. After building the most comprehensive phylogeny of the group, with almost 600 species and all higher taxa (subfamilies, tribes and subtribes), we found strong support for the following relationships within the family: Dismorphiinae + (Coliadinae + (Pseudopontiinae + Pierinae)). With a curated distribution dataset of over 800,000 occurrences, we conducted multiple comparative phylogenetic analyses that provided strong evidence that species in environments with more stable daily temperatures or with cooler maximum temperatures in the warm seasons have higher diversification rates. We also found a positive correlation between speciation and extinction with paleotemperature: as global temperature decreased through geological time, so did diversification rates. Although many studies demonstrate higher diversity in the tropics, we have been able to identify specific climate variables associated with changes in diversification, while also inferring the most robust and well sampled phylogenomic framework for Pieridae to date.
Luminal epithelial cells integrate variable responses to aging into stereotypical changes that underlie breast cancer susceptibility
Authors: Sayaman Rosalyn W. , Miyano Masaru , Senapati Parijat , Zirbes Arrianna , Shalabi Sundus , Todhunter Michael E. , Seewaldt Victoria , Neuhausen Susan L. , Stampfer Martha R. , Schones Dustin E. , LaBarge Mark A. 
Published: September 2022

AbstractEffects from aging in single cells are unpredictable, whereas aging phenotypes at the organ- and tissue-levels tend to appear as stereotypical changes. The mammary epithelium is a bilayer of two major phenotypically and functionally distinct cell lineages, the luminal epithelial and myoepithelial cells. Mammary epithelia exhibit substantial stereotypical changes with age that merits attention because they are putative breast cancer-cells-of-origin. We hypothesize that effects from aging that impinge upon maintenance of lineage fidelity increases susceptibility to cancer initiation. We identified two models of age-dependent changes in gene expression, directional changes and increased variance, which contributed to genome-wide loss of lineage fidelity. Age-dependent variant responses were common to both lineages, whereas directional changes were almost exclusively detected in luminal epithelia and implicated downregulation of chromatin and genome organizers such asSATB1. Epithelial expression of gap junction proteinGJB6increased with age, and modulation ofGJB6expression in heterochronous co-cultures revealed that it provided a communication conduit from myoepithelial cells that drove directional change in luminal cells. Age-dependent luminal transcriptomes comprised a prominent signal detectable in bulk tissue during aging and transition into cancers. A machine learning classifier based on luminal-specific aging distinguished normal from cancer tissue and was predictive of breast cancer subtype. We speculate that luminal epithelia are the ultimate site of integration of the variant responses to aging in their surrounding tissue and that their emergent aging phenotype both endows cells with the ability to become cancer-cells-of-origin and embodies a biosensor that presages cancer susceptibility.
Parvalbumin Neurons and Cortical Coding of Dynamic Stimuli: A Network Model
Authors: Nocon Jian Carlo , Boyd Isaac Paul , Gritton Howard , Han Xue , Sen Kamal 
Published: September 2022

AbstractCortical circuits feature both excitatory and inhibitory cells that underlie the encoding of dynamic sensory stimuli, e.g., speech, music, odors, and natural scenes. While previous studies have shown that inhibition plays an important role in shaping the neural code, how excitatory and inhibitory cells coordinate to enhance encoding of temporally dynamic stimuli is not fully understood. Recent experimental recordings in mouse auditory cortex have shown that optogenetic suppression of parvalbumin neurons results in a decrease of neural discriminability of dynamic stimuli. Here, we present a multilayer model of a cortical circuit that mechanistically explains these results. The model is based on parvalbumin neurons which respond to both stimulus onsets and offsets, as observed experimentally, and incorporates characteristic shortterm synaptic plasticity profiles of excitatory and parvalbumin neurons. We reveal that by tuning the relative strengths of onset and offset inputs to parvalbumin neurons, the model generates different regimes of coding dominated by rapid firing rate modulations or spike timing. Moreover, the model replicates the experimentally observed reduction in neural discrimination performance during optogenetic suppression of parvalbumin neurons. These results suggest that distinct onset and offset inputs to parvalbumin neurons enhance cortical discriminability of dynamic stimuli by encoding distinct temporal features, enhancing temporal coding, and reducing cortical noise.New & NoteworthyHere we propose a model for the mechanisms that underlie neuron responses in the auditory cortex. This study focuses on single channel tuning of simple interactions between neurons. Using physiologically relevant parameters that underly parvalbumin and excitatory neurons, in the proposed artificial network, we show that we can recreate observed results in live studies.
Natural variation in host defense strategies impacts both host and pathogen fitness
Authors: Pfenning-Butterworth Alaina C. , Vetter Rachel E. , Hite Jessica L. 
Published: September 2022

SummaryAnimals ranging from mosquitoes to humans often vary their feeding behavior when infected or merely exposed to pathogens. For example, some individuals drastically reduce their food intake (‘illness-mediated anorexia’) while others increase food intake (‘hyperphagia’). While these so-called ‘sickness behaviors’ are well documented, their functional consequences remain poorly resolved.Here, we examine links between natural genetic variation in susceptibility to infection, feeding behaviors, multiple traits of the host, and within-host pathogen production. Using a zooplankton host (Daphnia dentifera) and a fungal pathogen (Metschnikowia bicuspidata) as a case study, we show that genotypic and dose-dependent variation in feeding behaviors are associated with both resistance and tolerance mechanisms.In one genotype, immune-mediated anorexia was associated with increased tolerance to infection; unlike other genotypes, these individuals did not upregulate phenoloxidase activity, but lived longer, had the highest overall fecundity, and produced higher pathogen loads, despite their reduced growth rates and resultant smaller body sizes. In these hosts, peak parasite load remained unchanged, suggesting a tolerance mechanism that offset fecundity costs.In other genotypes, feeding behaviors followed either a flat or hump-shaped pattern with pathogen dose, exhibiting hyperphagia at intermediate doses and anorexia at higher doses. In these cases, anorexia functioned primarily in resistance.Our results suggest that infection-mediated changes in host feeding behavior — which are traditionally interpreted as immunopathology — may in fact serve as crucial components of host defense strategies. Moreover, these phenomena vary across host genotypes, and were associated with apparent trade-offs with another melanization component of immune defense. Together, these results underscore that while resistance and tolerance are typically viewed as alternative and fixed defense strategies, the immense genetic diversity for immune defense may result in more of a plastic spectrum spanning a gradient from resistance to tolerance.