bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strong early impact of letrozole on ovulation induction outperforms clomiphene citrate in polycystic ovary syndrome: a systematic review with meta-analysis
Authors: Vajna Rita Zsuzsanna , Géczi András Mihály , Meznerics Fanni Adél , Ács Nándor , Hegyi Péter , Feig Emma Zoé , Fehérvári Péter , Kiss-Dala Szilvia , Várbíró Szabolcs , Hetthessy Judit Réka , Sára Levente 
Published: September 2023

AbstractBackgroundPolycystic ovary syndrome is one of the most frequent endocrinological problems causing infertility in women worldwide. The main problem in these women is hyperandrogenism and/or chronic oligo/anovulation, which leads to infertility. In this systematic review and meta-analysis, we aimed to investigate the efficacy of a relatively new drug for ovulation induction, letrozole, by comparing it to the first line of treatment for ovulation induction, clomiphene citrate.MethodsA literary search was conducted in three databases and included randomized clinical trials comparing letrozole and clomiphene citrate for ovulation induction for women with polycystic ovary syndrome. The diagnosis of polycystic ovary syndrome was determined according to the Rotterdam criteria. We pooled data using a random-effects model.ResultsOur search provided a total of 1,994 articles, of which we included 25 studies. In the letrozole group, endometrial thickness was significantly higher (Mean Difference=1.70, Confidence Interval: 0.55-2.86; Heterogeinity: I2=97%, p-value=0.008); odds for ovulation (Odds Ratio=1.8, Confidence Interval: 1.21-2.69; Heterogeinity: I2=51%, p-value=0.010) and pregnancy (Odds Ratio=1.96, Confidence Interval: 1.37-2.81; Heterogeinity: I2=32%, p- value=0.002) were significantly higher; the resistance index of subendometrial arteries was significantly lower (Mean Difference=-0.15, Confidence Interval: -0.27- -0.04; Heterogeneity: I2=92%, p-value=0.030).ConclusionWomen with polycystic ovary syndrome treated with letrozole for ovulation induction had higher ovulation and pregnancy rates, their endometrium became thicker, the resistance index of subendometrial arteries was lower. The lower resistance index of the subendometrial arteries can improve intrauterine circulation, which may provide better circumstances for embryo implantation and development.
Deep learning to extract the meteorological by-catch of wildlife cameras
Authors: Alison Jamie , Payne Stephanie , Alexander Jake M. , Bjorkman Anne D. , Clark Vincent Ralph , Gwate Onalenna , Huntsaar Maria , Iseli Evelin , Lenoir Jonathan , Mann Hjalte Mads Rosenstand , Steenhuisen Sandy-Lynn , Høye Toke Thomas 
Published: September 2023

AbstractMicroclimate – proximal climatic variation at scales of meters and minutes – can exacerbate or mitigate the impacts of climate change on biodiversity. However, most microclimate studies are temperature-centric, and do not consider meteorological factors such as sunshine, hail and snow. Meanwhile, remote cameras have become a primary tool to monitor wild plants and animals, even at micro-scales, with deep learning tools to rapidly convert images into ecological data. However, deep learning applications for wildlife imagery have focused exclusively on living subjects. Here, we identify an overlooked opportunity to extract latent, yet ecologically relevant, meteorological information.We produce an annotated image dataset of micrometeorological conditions across 49 wildlife cameras in South Africa’s Maloti-Drakensberg and the Swiss Alps. We train ensemble deep learning models to classify conditions as overcast, sunshine, hail or snow. Our best model achieves 91.7% accuracy on test cameras not seen during training. Furthermore, we show how effective accuracy is raised to 96% by disregarding 14.1% of classifications where ensemble member models did not reach a consensus. Unlike previous studies we test model performance in remote and novel locations, distinguishing overcast and sunny conditions in Svalbard, Norway with 79.3% accuracy (93.9% consensus accuracy).Our model rapidly classifies sunshine, snow and hail in almost 2 million unlabeled images. Resulting micrometeorological data illustrated common seasonal patterns of summer hailstorms and autumn snowfalls across mountains in the northern and southern hemispheres. However, daily patterns of sunshine and shade diverged between sites, impacting daily temperature cycles. Crucially, we leverage micrometeorological data to demonstrate that (1) experimental warming using open-top chambers shortens early snow events in autumn, and (2) image-derived sunshine marginally outperforms sensor-derived temperature when predicting bumblebee foraging. These methods generate novel micrometeorological variables in synchrony with biological recordings, enabling new insights from an increasingly global network of wildlife cameras.
PanEffect: A pan-genome visualization tool for variant effects in maize
Authors: Andorf Carson M , Haley Olivia C , Hayford Rita K , Portwood John L , Sen Shatabdi , Cannon Ethalinda K , Gardiner Jack M , Woodhouse Margaret R 
Published: September 2023

AbstractUnderstanding the effects of genetic variants is crucial for accurately predicting traits and phenotypic outcomes. Recent advances have utilized protein language models to score all possible missense variant effects at the proteome level for a single genome, but a reliable tool is needed to explore these effects at the pan-genome level. To address this gap, we introduce a new tool called PanEffect. We implemented PanEffect at MaizeGDB to enable a comprehensive examination of the potential effects of coding variants across 51 maize genomes. The tool allows users to visualize over 550 million possible amino acid substitutions in the B73 maize reference genome and also to observe the effects of the 2.3 million natural variations in the maize pan-genome. Each variant effect score, calculated from the Evolutionary Scale Modeling (ESM) protein language model, shows the log-likelihood ratio difference between B73 and all variants in the pan-genome. These scores are shown using heatmaps spanning benign outcomes to strong phenotypic consequences. Additionally, PanEffect displays secondary structures and functional domains along with the variant effects, offering additional functional and structural context. Using PanEffect, researchers now have a platform to explore protein variants and identify genetic targets for crop enhancement.Availability and implementation: The PanEffect code is freely available on GitHub (https://github.com/Maize-Genetics-and-Genomics-Database/PanEffect). A maize implementation of PanEffect and underlying datasets are available at MaizeGDB (https://www.maizegdb.org/effect/maize/).
Generative Diffusion Models for Antibody Design, Docking, and Optimization
Authors: Peng Zhangzhi , Han Chenchen , Wang Xiaohan , Li Dapeng , Yuan Fajie 
Published: September 2023

AbstractIn recent years, optimizing antibody binding affinity for biomedical applications has become increasingly important. However, traditional wet-experiment-based approaches are time-consuming and inefficient. To address this issue, we propose a diffusion model-based antibody optimization pipeline to improve binding affinity. Our approach involves two key models: AbDesign for designing antibody sequences and structures, and AbDock, a paratope-epitope docking model, used for screening designed CDRs. On an independent test set, our AbDesign demonstrates the exceptional performance of an RMSD of 2.56Å in structure design and an amino acid recovery of 36.47% in sequence design. In a paratope-epitope docking test set, our AbDock achieves a state-of-the-art performance of DockQ 0.44, irms 2.71Å, fnat 0.40, and Lrms 6.29Å. The effectiveness of the optimization pipeline is further experimentally validated by optimizing a flaviviruse antibody 1G5.3, resulting in a broad-spectrum antibody that demonstrates improved binding to 6 out of the nine tested flaviviruses. This research offers a general-purpose methodology to enhance antibody functionality without training on data from specific antigens.
TheMUC19gene in Denisovans, Neanderthals, and Modern Humans: An Evolutionary History of Recurrent Introgression and Natural Selection
Authors: Villanea Fernando A. , Peede David , Kaufman Eli J. , Añorve-Garibay Valeria , Chevy Elizabeth T. , Villa-Islas Viridiana , Witt Kelsey E. , Zeloni Roberta , Marnetto Davide , Moorjani Priya , Jay Flora , Valdmanis Paul N. , Ávila-Arcos María C. , Huerta-Sánchez Emilia 
Published: September 2023

AbstractWe study the gene MUC19, for which modern humans carry a Denisovan-like haplotype. MUC19 is a mucin, a glycoprotein that forms gels with various biological functions. We find the diagnostic variants for the Denisovan-like MUC19 haplotype at high frequencies in admixed Latin American individuals among global populations, and at highest frequency in 23 ancient Indigenous American individuals, all predating population admixture with Europeans and Africans. We find that the Denisovan-like MUC19 haplotype carries a higher copy number of a 30 base-pair variable number tandem repeat, and that copy numbers of this repeat are exceedingly high in American populations and are under positive selection. This study provides the first example of positive selection acting on archaic alleles at coding sites and VNTRs. Finally, we find that some Neanderthals carry the Denisovan-like MUC19 haplotype, and that it was likely introgressed into human populations through Neanderthal introgression rather than Denisovan introgression.One-Sentence SummaryModern humans and Neanderthals carry a Denisovan variant of theMUC19gene, which is under positive selection in populations of Indigenous American ancestry.
Maresin-1 promotes neuroprotection and prevents disease progression in experimental models of multiple sclerosis through metabolic reprogramming and shaping innate and adaptive disease-associated cell types
Authors: Zahoor Insha , Nematullah Mohammad , Ahmed Mohammad Ejaz , Fatma Mena , Mir Sajad , Ayasolla Kamesh , Cerghet Mirela , Palaniyandi Suresh , Ceci Veronica , Carrera Giulia , Buttari Fabio , Centonze Diego , Mao-Draayer Yang , Rattan Ramandeep , Chiurchiù Valerio , Giri Shailendra 
Published: September 2023

AbstractMultiple sclerosis (MS) is one of the most common inflammatory neurodegenerative diseases in young adults and causes neurological abnormalities and disability. We studied the effect of maresin 1 (MaR1) on the progression of disease in a relapsing-remitting form of experimental allergic encephalomyelitis (RR-EAE). Treatment with MaR1 in RR-EAE accelerated inflammation resolution, protected against neurological deficits, and delayed disease progression by decreasing immune cell infiltration (CD4+IL17+ and CD4+IFNγ+) into the CNS. Furthermore, the administration of MaR1 increased the production of IL-10, predominantly in macrophages and CD4+ cells. However, neutralizing IL-10 with an anti-IL-10 antibody abolished the protective effect of MaR1 on RR-EAE, suggesting that IL-10 plays a role in mediating the protective effect of MaR1 on EAE. Metabolism is rapidly becoming recognized as an important factor influencing the effector function of many immune cells. Using cutting-edge metabolic assays, our study revealed that compared with vehicle treatment, MaR1 treatment effectively restored the metabolic dysregulation observed in CD4+ cells, macrophages, and microglia in the treated group. Furthermore, MaR1 treatment reversed defective efferocytosis in EAE mice, which was potentially facilitated by the induction of metabolic alterations in macrophages and microglia. MaR1 treatment also protected myelin in the EAE group and regulated the metabolism of O4+ oligodendrocytes by restoring metabolic dysregulation through improved mitochondrial function and decreased glycolysis. Overall, in a preclinical MS animal model, MaR1 treatment produced anti-inflammatory and neuroprotective effects. It also triggered metabolic reprogramming in disease-associated cell types, accelerated efferocytosis, and preserved myelination. These data support that MaR1 has potential as a novel treatment agent for MS and other autoimmune diseases.Abstract FigureHighlightsMaR1 expedited inflammation resolution and prevented neurological impairments in RR-EAE.IL-10 plays a role in mediating the protective effect of MaR1 on EAE.MaR1 repaired CD4, macrophage, and microglia metabolic abnormalities.MaR1 therapy restored efferocytosis in EAE.MaR1 preserved myelin and improved O4+ oligodendrocyte metabolism.
Host-pathogen-vector continuum in a changing landscape: Drivers ofBartonellaprevalence and evidence of historic spillover in a multi-host community
Authors: Ansil B.R. , Viswanathan Ashwin , Ramachandran Vivek , Yeshwanth H.M. , Sanyal Avirup , Ramakrishnan Uma 
Published: September 2023

AbstractSmall mammals and their ectoparasites present a unique system to investigate the eco-epidemiology of multi-host vector-borne pathogens and identify specific bacterial spillover determinants. We applied ecological and evolutionary analyses in a rainforest-human-use mosaic to investigateBartonella spp.across small mammal and ectoparasite communities. We observed substantial overlap among small mammal communities in different habitat types, predominantly driven by habitat generalists. Most ectoparasites were generalists, infecting multiple hosts. We observed highBartonellaprevalence at both study sites –a forest-plantation mosaic (47.4%) and a protected area (28.8%). Seven of the ten ectoparasite species sampled were also positive forBartonella, following prevalence trends in their hosts. A generalised linear model revealed an independent association between aggregated ectoparasite load in hosts andBartonellaprevalence, implicating ectoparasites in transmission.Bartonellalineages from small mammals were host-specific, while ectoparasites carriedBartonellaassociated with other small mammal hosts, indicating the potential for cross-species transmission. Phylogenetic ancestral trait reconstruction ofBartonellahaplotypes suggest historic spillover events in the small mammal community, validating the potential for contemporary spillover events. These results highlight the necessity to disentangle the complex relationship between hosts, ectoparasites, and pathogens to understand the zoonotic implications of undetected spillover events in such multi-host communities.
Oxytocin, but not vasopressin, decreases willingness to harm others by promoting moral emotions of guilt and shame
Authors: Zheng Xiaoxiao , Wang Jiayuan , Yang Xi , Xu Lei , Becker Benjamin , Sahakian Barbara J. , Robbins Trevor W. , Kendrick Keith M. 
Published: September 2023

AbstractProsocial and moral behaviors have overlapping neural systems but whether they involve similar neurochemical systems is unclear. In the current pre-registered randomized placebo controlled trial on 180 adult male and female subjects we investigated effects of intranasal administration of two prosocial neuropeptides, oxytocin or vasopressin, on moral emotion ratings for situations involving accidental or intentional harm to others and in judgments of moral dilemmas where harm is inflicted for a greater good. Oxytocin, but not vasopressin, enhanced feelings of guilt and shame only for intentional harm and reduced endorsement of choices where direct intentional harm to others could achieve a greater good. Effects of oxytocin on guilt and shame were partially mediated by trait empathy. Overall, findings demonstrate for the first time that oxytocin, but not vasopressin, promotes unwillingness to deliberately harm others irrespective of the consequences. This may reflect stronger associations between oxytocin and empathy and vasopressin with aggression.
A gut meta-interactome map reveals modulation of human immunity by microbiome effectors
Authors: Young Veronika , Dohai Bushra , Hitch Thomas C. A. , Hyden Patrick , Weller Benjamin , van Heusden Niels S. , Saha Deeya , Macgregor Jaime Fernandez , Maseko Sibusiso B. , Lin Chung-Wen , Boujeant Mégane , Choteau Sébastien A. , Ober Franziska , Schwehn Patrick , Rothballer Simin , Altmann Melina , Altmann Stefan , Strobel Alexandra , Rothballer Michael , Tofaute Marie , Heinig Matthias , Clavel Thomas , Twizere Jean-Claude , Vincentelli Renaud , Boes Marianne , Krappmann Daniel , Falter Claudia , Rattei Thomas , Brun Christine , Zanzoni Andreas , Falter-Braun Pascal 
Published: September 2023

SUMMARYThe molecular mechanisms by which the gut microbiome influences human health remain largely unknown. Pseudomonadota is the third most abundant phylum in normal gut microbiomes. Several pathogens in this phylum can inject so-called virulence effector proteins into host cells. We report the identification of intact type 3 secretion systems (T3SS) in 5 - 20% of commensal Pseudomonadota in normal human gut microbiomes. To understand their functions, we experimentally generated a high-quality protein-protein meta-interactome map consisting of 1,263 interactions between 289 bacterial effectors and 430 human proteins. Effector targets are enriched for metabolic and immune functions and for genetic variation of microbiome-influenced traits including autoimmune diseases. We demonstrate that effectors modulate NF-κB signaling, cytokine secretion, and adhesion molecule expression. Finally, effectors are enriched in metagenomes of Crohn’s disease, but not ulcerative colitis patients pointing toward complex contributions to the etiology of inflammatory bowel diseases. Our results suggest that effector-host protein interactions are an important regulatory layer by which the microbiome impacts human health.
Uncertainty-aware single-cell annotation with a hierarchical reject option
Authors: Theunissen Lauren , Mortier Thomas , Saeys Yvan , Waegeman Willem 
Published: September 2023

AbstractAutomatic cell type annotation methods assign cell type labels to new datasets by extracting relationships from a reference RNA-seq dataset. However, due to the limited resolution of gene expression features, there is always uncertainty present in the label assignment. To enhance the reliability and robustness of annotation, most machine learning methods address this uncertainty by providing a full reject option, i.e. when the predicted confidence score of a cell type label falls below a user-defined threshold, no label is assigned and no prediction is made. As a better alternative, some methods deploy hierarchical models and consider a so-called partial rejection by returning internal nodes of the hierarchy as label assignment. However, because a detailed experimental analysis of various rejection approaches is missing in the literature, there is no consensus on best practices, superiority of certain methods, and potential drawbacks associated with rejection. We evaluate three annotation approaches (1) full rejection (2) partial rejection and (3) no rejection for both flat and hierarchical probabilistic classifiers. Our findings indicate that hierarchical classifiers are superior when rejection is applied, with partial rejection being the preferred rejection approach, as it preserves a significant amount of label information. For optimal rejection implementation, the rejection threshold should be determined through careful examination of a method’s rejection behavior. Without rejection, flat and hierarchical annotation perform equally well, as long as the cell type hierarchy accurately captures transcriptomic relationships.
White matter tract microstructure, macrostructure, and associated cortical gray matter morphology across the lifespan
Authors: Schilling Kurt G , Chad Jordan A. , Chamberland Maxime , Nozais Victor , Rheault Francois , Archer Derek , Li Muwei , Gao Yurui , Cai Leon , Del’Acqua Flavio , Newton Allen , Moyer Daniel , Gore John C. , Lebel Catherine , Landman Bennett A 
Published: September 2023

AbstractCharacterizing how, when and where the human brain changes across the lifespan is fundamental to our understanding of developmental processes of childhood and adolescence, degenerative processes of aging, and divergence from normal patterns in disease and disorders. We aimed to provide detailed descriptions of white matter pathways across the lifespan by thoroughly characterizing white mattermicrostructure, white mattermacrostructure, and morphology of thecortexassociated with white matter pathways. We analyzed 4 large, high-quality, publicly-available datasets comprising 2789 total imaging sessions, and participants ranging from 0 to 100 years old, using advanced tractography and diffusion modeling. We first find that all microstructural, macrostructural, and cortical features of white matter bundles show unique lifespan trajectories, with rates and timing of development and degradation that vary across pathways – describing differences between types of pathways and locations in the brain, and developmental milestones of maturation of each feature. Second, we show cross-sectional relationships between different features that may help elucidate biological changes occurring during different stages of the lifespan. Third, we show unique trajectories of age-associations across features. Finally, we find that age associations during development are strongly related to those during aging. Overall, this study reports normative data for several features of white matter pathways of the human brain that will be useful for studying normal and abnormal white matter development and degeneration.
BioXTAS RAW 2: new developments for a free open-source program for small angle scattering data reduction and analysis
Authors: Hopkins Jesse B. 
Published: September 2023

AbstractBioXTAS RAW is a free, open-source program for reduction, analysis and modelling of biological small angle scattering data. Here, the new developments in RAW version 2 are described. These include: improved data reduction using pyFAI; updated automated Guinier fitting andDmaxfinding algorithms; automated series (e.g. SEC-SAXS) buffer and sample region finding algorithms; linear and integral baseline correction for series; deconvolution of series data using REGALS; creation of electron density reconstructions via DENSS; a comparison window showing residuals, ratios, and statistical comparisons between profiles; and generation of PDF reports with summary plots and tables for all analysis. In addition, there is now a RAW API, which can be used without the GUI, providing full access to all of the functionality found in the GUI. In addition to these new capabilities, RAW has undergone significant technical updates, such as adding Python 3 compatibility, and has entirely new documentation available both online and in the program.