bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Single-cell and Spatial RNA-seq Database for Alzheimer’s Disease (ssREAD)
Authors: Wang Cankun , Acosta Diana , McNutt Megan , Bian Jiang , Ma Anjun , Fu Hongjun , Ma Qin 
Published: September 2023

AbstractAlzheimer’s Disease (AD) pathology has been increasingly explored through single-cell and single-nucleus RNA-sequencing (scRNA-seq & snRNA-seq) and spatial transcriptomics (ST). However, the surge in data demands a comprehensive, user-friendly repository. Addressing this, we introduce a single-cell and spatial RNA-seq database for Alzheimer’s disease (ssREAD). It offers a broader spectrum of AD-related datasets, an optimized analytical pipeline, and improved usability. The database encompasses 1,053 samples (277 integrated datasets) from 67 AD-related scRNA-seq & snRNA-seq studies, totaling 7,332,202 cells. Additionally, it archives 381 ST datasets from 18 human and mouse brain studies. Each dataset is annotated with details such as species, gender, brain region, disease/control status, age, and AD Braak stages. ssREAD also provides an analysis suite for cell clustering, identification of differentially expressed and spatially variable genes, cell-type-specific marker genes and regulons, and spot deconvolution for integrative analysis. ssREAD is freely available athttps://bmblx.bmi.osumc.edu/ssread/.
Improved Super-Resolution Ribosome Profiling Revealed Prevalent Translation of Upstream ORFs and Small ORFs in Arabidopsis
Authors: Wu Hsin-Yen Larry , Ai Qiaoyun , Teixeira Rita Teresa , Song Gaoyuan , Montes Christian , Elmore J. Mitch , Walley Justin W. , Hsu Polly Yingshan 
Published: September 2023

ABSTRACTA crucial step in functional genomics is identifying actively translated open reading frames (ORFs) that link biological functions. The challenge lies in identifying short ORFs, as they are greatly impacted by data quality and depth. Here, we improved the coverage of super-resolution Ribo-seq in Arabidopsis, revealing uncharacterized translation events in nucleus-, chloroplast-, and mitochondria-encoded genes. We identified 7,751 unconventional translation events, including 6,996 upstream ORFs (uORFs) and 209 downstream ORFs on annotated protein-coding genes, as well as 546 ncORFs on presumed non-coding RNAs. Proteomics data confirmed the production of stable proteins from some of the unannotated translation events. We present evidence of active translation on primary transcripts of tasiRNAs (TAS1-4) and microRNAs (pri-miR163, pri-miR169), and periodic ribosome stalling supporting co-translational decay. Additionally, we developed a method for identifying extremely short uORFs, including 370 minimum uORF (AUG-stop), and 2,984 tiny uORFs (2-10 aa), as well as 681 uORFs that overlap with each other. Remarkably, these short uORFs exhibit strong translational repression as longer uORFs. We also systematically discovered 594 uORFs regulated by alternative splicing, suggesting widespread isoform-specific translational control. Finally, these prevalent uORFs are associated with numerous important pathways. In summary, our improved Arabidopsis translational landscape provides valuable resources to study gene expression regulation.
Comparison of the microbiome and mycobiome in tissues of the tropical carnivorous epiphytic herbUtricularia jamesoniana
Authors: Naranjo-Aguilar Valeria , Mora-Castro Rebeca , Morera-Huertas Jessica , Acuña-Castillo Rafael H. , Rojas-Jimenez Keilor 
Published: September 2023

AbstractUtricularia jamesoniana, a small epiphytic plant found in wet tropical forests, stands out for its carnivorous habit, intricate trap system, and small but beautiful and complex flowers. This species remains relatively understudied despite its wide geographical distribution and curious adaptations. In this study, we employed 16S rRNA and ITS sequencing to compare the prokaryotic and fungal communities within leaves and traps ofU. jamesoniana. The analysis of amplicon sequence variants (ASVs) unveiled notable differences in community composition depending on the plant tissue and type of microorganism. Prokaryotic communities predominantly comprised Proteobacteria and Actinobacteriota, featuring genera such asAcidocella, Bradyrhizobium, Ferritrophicum, andFerrovum. Fungal communities were dominated by Ascomycota and Basidiomycota, encompassing representatives of Dothideomycetes, Sordariomycetes, Eurotiomycetes, and Agaricomycetes, as well as ASVs related to Mycosphaerellaceae,Colletotrichum, Aspergillus, andThanatephorus. We determined that the prokaryotic diversity has higher in the bladders with respect to the leaves. Fungal communities, in turn, were more diverse in leaves than in bladders. This study sheds light on the microbial communities associated with this carnivorous epiphyte and provides valuable insights into the intricate relationships between the plant and its microbial inhabitants across different tissues.
Effects of a high cholesterol diet onDrosophilachill tolerance are highly context-dependent
Authors: Allen Mitchell C. , Ritchie Marshall W. , El-Saadi Mahmoud I. , MacMillan Heath A. 
Published: September 2023

AbstractChill susceptible insects are thought to be injured through different mechanisms depending on the duration and severity of chilling. While chronic chilling causes “indirect” injury through disruption of metabolic and ion homeostasis, acute chilling is suspected to cause “direct” injury, in part through phase transitions of cell membrane lipids. Dietary supplementation of cholesterol can reduce acute chilling injury inDrosophila melanogaster, but the generality of this effect and the mechanisms underlying it remain unclear. To better understand how and why cholesterol has this effect, we assessed how a high cholesterol diet and thermal acclimation independently and interactively impact several measures of chill tolerance in both male and female flies. Cholesterol supplementation positively affected tolerance to acute chilling in warm-acclimated flies (as reported previously). Conversely, feeding on the high-cholesterol diet negatively affected tolerance to chronic chilling in both cold and warm acclimated flies, as well as tolerance to acute chilling in cold acclimated flies. Cholesterol had no effect on the ability of flies to remain active in the cold or recover movement after a cold stress. Our findings support the idea that dietary cholesterol reduces mechanical injury to membranes caused by direct chilling injury, and that acute and chronic chilling are associated with distinct mechanisms of injury. Feeding on a high-cholesterol diet may interfere with mechanisms involved in cold acclimation, leaving cholesterol augmented flies more susceptible to chilling injury under some conditions.HighlightsCholesterol improves cold shock tolerance of warm-acclimated fliesCold acclimation and chronic cold instead lead to negative effects of cholesterol on chill toleranceCholesterol did not affect the ability of flies to remain active in the coldBoth sexes were similarly affected by a high cholesterol diet
Effectiveness of SGLT2 inhibitor therapy in treatment of Heart failure: A Meta-Analysis
Authors: Albalushi Sarvinoz , Zarif Azmaeen , Karaduman Suheyla , Tran Khoa , Talpeka Alesia 
Published: September 2023

AbstractAimWe conducted a meta-analysis on the effectiveness of sodium-glucose co-transporter 2 (SGLT2) inhibitors in heart failure (HF) patients with preserved (HFpEF) and reduced (HFrEF) ejection fraction.MethodsA comprehensive search of several databases for placebo-controlled randomised controlled trials of SGLT2 inhibitors from inception to September 30 2022, limited to English language and excluding animal studies, was conducted. The databases included Medline, Scopus, Cochrane Central, and ClinicalTrials.gov. Randomised controlled studies were chosen if they included HF patients and reported at least one of the predetermined outcomes. Hazard ratios (HRs) or risk ratios were pooled together with the appropriate 95% confidence intervals using a random-effect model. Fourteen trials met the inclusion criteria, with 42 409 HF patients participating (N = 21 678 in the SGLT2 inhibitor arms and N = 20 731 in the placebo arms).ResultsSGLT2 inhibitors significantly reduced the composite of HF hospitalisation or cardiovascular death [HR: 0.75 (0.71–0.79);P< 0.001;I2= 0%], total hospitalisations for heart failure [HR: 0.70 (0.66– 0.75);P< 0.001;I2= 0%], and reduced the occurrence of cardiovascular death [HR: 0.86 (0.81–0.92);P< 0.001;I2= 43%]. Sub-group analysis was conducted based on HF status at baseline, EF, diabetes status at baseline, and sex. SGLT2 inhibitors significantly reduced the composite heart failure hospitalisation and cardiovascular death for all the subgroups except for patients with HFpEF at baseline [HR: 0.87 (0.74– 1.03);P= 0.11;I2= 60%] and no diabetes status at baseline [HR: 0.92 (0.73–1.16);P= 0.50;I2= 78%].ConclusionsIn patients with HF, SGLT2 inhibitors may significantly improve clinical outcomes, including all-cause and cardiovascular mortality. In this meta-analysis, SGLT2 inhibitors did not show a reduction in composite heart failure in patients with heart failure with preserved ejection fraction at baseline.
Myosin-binding protein C forms C-links and stabilizes OFF states of myosin
Authors: Hessel Anthony L. , Engels Nichlas M. , Kuehn Michel , Nissen Devin , Sadler Rachel L. , Ma Weikang , Irving Thomas C. , Linke Wolfgang A. , Harris Samantha P. 
Published: September 2023

AbstractContraction force in muscle is produced by the interaction of myosin motors in the thick filaments and actin in the thin filaments and is fine-tuned by other proteins such as myosin-binding protein C (MyBP-C). One form of control is through the regulation of myosin heads between an ON and OFF state in passive sarcomeres, which leads to their ability or inability to interact with the thin filaments during contraction, respectively. MyBP-C is a flexible and long protein that is tightly bound to the thick filament at its C-terminal end but may be loosely bound at its middle- and N-terminal end (MyBP-CC1C7). Under considerable debate is whether the MyBP-CC1C7domains directly regulate myosin head ON/OFF states, and/or link thin filaments (“C-links”). Here, we used a combination of mechanics and small-angle X-ray diffraction to study the immediate and selective removal of the MyBP-CC1C7domains of fast MyBP-C in permeabilized skeletal muscle. After cleavage, the thin filaments were significantly shorter, a result consistent with direct interactions of MyBP-C with thin filaments thus confirming C-links. Ca2+sensitivity was reduced at shorter sarcomere lengths, and crossbridge kinetics were increased across sarcomere lengths at submaximal activation levels, demonstrating a role in crossbridge kinetics. Structural signatures of the thick filaments suggest that cleavage also shifted myosin heads towards the ON state – a marker that typically indicates increased Ca2+sensitivity but that may account for increased crossbridge kinetics at submaximal Ca2+and/or a change in the force transmission pathway. Taken together, we conclude that MyBP-CC1C7domains play an important role in contractile performance which helps explain why mutations in these domains often lead to debilitating diseases.
Complete Chloroplast Genome of a Montane PlantSpathoglottis aureaLindl.: Comparative Analyses and Phylogenetic Relationships among members of Tribe Collabieae
Authors: Talkah Nurul Shakina Mohd , Jasim Jasim Haider Mahmod , Nordin Farah Alia , Othman Ahmad Sofiman 
Published: September 2023

AbstractThe yellow–floweredSpathoglottis aurea(tribe Collabieae; family Orchidaceae) is native to the mountainous areas of Peninsular Malaysia. The species is well known as an ornamental plant and for its role in artificial hybrid breeding. There is an interesting evolutionary relationship betweenS. aureaand the geographically isolatedS. microchilinafrom Borneo that has encouraged further study of theS. aureapopulations, but the genomic resource forS. aureahas not yet been reported. The present study reports the first work to characterize a chloroplast genome among theSpathoglottisgenus. The complete chloroplast (cp) genome ofS. aureawas assembled from a sequence generated by the Illumina platform and analysed in comparison with other Collabieae species available in the GenBank database. The cp genome ofS. aureais 157,957 base pairs (bp) in length with guanine-cytosine (GC) content of 37.3%. The genome possessed a typical quadripartite chloroplast genome structure with large single-copy (LSC) (86,888 bp), small single-copy (SSC) (18,125 bp) and inverted repeat (IR) (26,472 bp) sequences. A total of 134 genes were annotated, with 88 protein coding genes (PCGs), 38 transfer RNA (tRNA) genes and eight ribosomal RNA (rRNA) genes. Overall, 80 simple sequence repeats (SSR) or microsatellites were identified. Comparative analysis with other Collabieae species revealed high conservation in the cp genome arrangements with minimal difference in genome lengths. However, several mutational hotspots were also detected, with high potential to be developed as genetic markers for phylogenetic analysis. Characterization of theS. aureacp genome revealed its conserved nature without gene loss or rearrangements when compared to other species of the Collabieae tribe. Phylogenetic analysis of Collabieae species also revealed thatS. aureahas a distant evolutionary relationship to other members of the Collabieae species, despite the presence of problematic genera such asPhaiusandCephalantheropsis.
Genetics of Congenitally Corrected Transposition of the Great Arteries: next generation sequencing shows a mutation load effect for 156 genes involved in cardiac patterning
Authors: Benadjaoud Yasmine , Benko Sabina , Hanin Fabienne Jabot , Audain Enrique , Deleuze Jean François , Boland Anne , Bole Christine , Bras Marc , Bajolle Fanny , Derouk Morgan , Gordon Christopher T. , Hitz Marc Phillip , Bonnet Damien , Lyonnet Stanislas 
Published: September 2023

AbstractCongenital heart disease (CHD) is a major public health issue. It is considered as a major cause of infant mortality today.We focused on a complex and rare CHD, the congenitally corrected transposition of the great arteries (CCTGA).The aim of this study was to identify the genes that control the alignment of cardiac chambers that are abnormal in CCTGA to further understand the mechanism of this CHD.We analyzed a cohort of 43 CCTGA cases (41 sporadic cases and 2 familial cases) of isolated CCTGA by next generation sequencing analysis (whole-genome sequencing and whole-exome sequencing).Under the hypothesis of Mendelian model includingde novogenomic alterations, no major gene effect involved in the disease could be identified.Under the hypothesis of a complex model of inheritance, we highlighted a group of 156 cardiac mutated genes in our patients, in which we found a significant enrichment of rare variants in patients compared to controls in a replication cohort. The highly heterogeneous combinations of susceptibility rare variants, mostly inherited from the healthy mother and father respectively, are correlated with the CCTGA phenotype, any given deleterious variant combination within the CCTGA gene set being specific to the affected individual.Taken together, the cases could be explained by a mutation load of segregated alleles at loci mostly involved in heart tubelooping, outflow tract morphogenesis and establishment of left-right asymmetry. Our data suggest that CHD are not Mendelian traits, but rather of polygenic origin. In the majority of cases, both parents harbour a set of susceptibility alleles for the CHD that are inherited by the offspring in a combination that confers the risk of CCTGA.
Multimodal mental health assessment with remote interviews using facial, vocal, linguistic, and cardiovascular patterns
Authors: Jiang Zifan , Seyedi Salman , Griner Emily , Abbasi Ahmed , Bahrami Rad Ali , Kwon Hyeokhyen , Cotes Robert O. , Clifford Gari D. 
Published: September 2023

AbstractObjectiveThe current clinical practice of psychiatric evaluation suffers from subjectivity and bias, and requires highly skilled professionals that are often unavailable or unaffordable. Objective digital biomarkers have shown the potential to address these issues. In this work, we investigated whether behavioral and physiological signals, extracted from remote interviews, provided complimentary information for assessing psychiatric disorders.MethodsTime series of multimodal features were derived from four conceptual modes: facial expression, vocal expression, linguistic expression, and cardiovascular modulation. The features were extracted from simultaneously recorded audio and video of remote interviews using task-specific and foundation models. Averages, standard deviations, and hidden Markov model-derived statistics of these features were computed from 73 subjects. Four binary classification tasks were defined: detecting 1) any clinically-diagnosed psychiatric disorder, 2) major depressive disorder, 3) self-rated depression, and 4) self-rated anxiety. Each modality was evaluated individually and in combination.ResultsStatistically significant feature differences were found between controls and subjects with mental health conditions. Correlations were found between features and self-rated depression and anxiety scores. Visual heart rate dynamics achieved the best unimodal performance with areas under the receiver-operator curve (AUROCs) of 0.68-0.75 (depending on the classification task). Combining multiple modalities achieved AUROCs of 0.72-0.82. Features from task-specific models outperformed features from foundation models.ConclusionMultimodal features extracted from remote interviews revealed informative characteristics of clinically diagnosed and self-rated mental health status.SignificanceThe proposed multimodal approach has the potential to facilitate objective, remote, and low-cost assessment for low-burden automated mental health services.
Finding Long-COVID: Temporal Topic Modeling of Electronic Health Records from the N3C and RECOVER Programs
Authors: O’Neil Shawn T. , Madlock-Brown Charisse , Wilkins Kenneth J. , McGrath Brenda M. , Davis Hannah E. , Assaf Gina S. , Wei Hannah , Zareie Parya , French Evan T. , Loomba Johanna , McMurry Julie A. , Zhou Andrea , Chute Christopher G. , Moffitt Richard A. , Pfaff Emily R , Yoo Yun Jae , Leese Peter , Chew Robert F. , Lieberman Michael , Haendel Melissa A. 
Published: September 2023

AbstractPost-Acute Sequelae of SARS-CoV-2 infection (PASC), also known as Long-COVID, encompasses a variety of complex and varied outcomes following COVID-19 infection that are still poorly understood. We clustered over 600 million condition diagnoses from 14 million patients available through the National COVID Cohort Collaborative (N3C), generating hundreds of highly detailed clinical phenotypes. Assessing patient clinical trajectories using these clusters allowed us to identify individual conditions and phenotypes strongly increased after acute infection. We found many conditions increased in COVID-19 patients compared to controls, and using a novel method to associate patients with clusters over time, we additionally found phenotypes specific to patient sex, age, wave of infection, and PASC diagnosis status. While many of these results reflect known PASC symptoms, the resolution provided by this unprecedented data scale suggests avenues for improved diagnostics and mechanistic understanding of this multifaceted disease.
Single-cell analysis of psoriasis resolution reveals an inflammatory fibroblast state targeted by IL-23 blockade
Authors: Francis Luc , McCluskey Daniel , Ganier Clarisse , Jiang Treasa , Du-Harpur Xinyi , Gabriel Jeyrroy , Dhami Pawan , Kamra Yogesh , Visvanathan Sudha , Barker Jonathan N. , Smith Catherine H. , Capon Francesca , Mahil Satveer K. 
Published: September 2023

AbstractBiologics targeting the IL-23/IL-17 axis have transformed the treatment of psoriasis. However, the early mechanisms of action of these drugs remain poorly understood. Here, we performed longitudinal single-cell RNA-sequencing in affected individuals receiving IL-23 inhibitor therapy. By profiling skin at baseline, day 3 and day 14 of treatment, we demonstrated that IL-23 blockade causes marked gene expression shifts, with fibroblast and myeloid populations displaying the most extensive changes at day 3. We also identified a transientWNT5A+/IL24+fibroblast state, which was only detectable in lesional skin.In-silicoandin-vitrostudies indicated that signals stemming from theseWNT5A+/IL24+fibroblasts upregulated multiple inflammatory genes in keratinocytes. Importantly, the abundance ofWNT5A+/IL24+fibroblasts was significantly reduced after treatment. This observation was validatedin-silico, by deconvolution of multiple transcriptomic datasets, and experimentally, by RNAin-situhybridization. These findings demonstrate that the evolution of inflammatory fibroblast states is a key feature of resolving psoriasis skin.
Spatial and temporal pattern of structure-function coupling of human brain connectome with development
Authors: Feng Guozheng , Wang Yiwen , Huang Weijie , Chen Haojie , Cheng Jian , Shu Ni 
Published: September 2023

AbstractBrain structural circuitry shapes a richly patterned functional synchronization, supporting for complex cognitive and behavioural abilities. However, how coupling of structural connectome (SC) and functional connectome (FC) develops and its relationships with cognitive functions and transcriptomic architecture remain unclear. We used multimodal magnetic resonance imaging data from 439 participants aged 5.7 to 21.9 years to predict functional connectivity by incorporating intracortical and extracortical structural connectivity, characterizing SC-FC coupling. Our findings revealed that SC-FC coupling was strongest in the visual and somatomotor networks, consistent with evolutionary expansion, myelin content, and functional principal gradient. As development progressed, SC-FC coupling exhibited heterogeneous alterations dominated by an increase in cortical regions, broadly distributed across the somatomotor, frontoparietal, dorsal attention, and default mode networks. Moreover, we discovered that SC-FC coupling significantly predicted individual variability in general intelligence, mainly influencing frontoparietal and default mode networks. Finally, our results demonstrated that the heterogeneous development of SC-FC coupling is positively associated with genes in oligodendrocyte-related pathways and negatively associated with astrocyte-related genes. This study offers insight into the maturational principles of SC-FC coupling in typical development.
Syntaxin 17 recruitment to mature autophagosomes is temporally regulated by PI4P accumulation
Authors: Shinoda Saori , Sakai Yuji , Matsui Takahide , Uematsu Masaaki , Koyama-Honda Ikuko , Sakamaki Jun-ichi , Yamamoto Hayashi , Mizushima Noboru 
Published: September 2023

AbstractDuring macroautophagy, cytoplasmic constituents are engulfed by autophagosomes. Lysosomes fuse with closed autophagosomes but not with unclosed intermediate structures. This is achieved in part by the late recruitment of the autophagosomal SNARE syntaxin 17 (STX17) to mature autophagosomes. However, how STX17 recognizes autophagosome maturation is not known. Here, we show that this temporally regulated recruitment of STX17 depends on the positively charged C-terminal region of STX17. Consistent with this finding, mature autophagosomes are more negatively charged compared with unclosed intermediate structures. This electrostatic maturation of autophagosomes is likely driven by the accumulation of phosphatidylinositol 4-phosphate (PI4P) in the autophagosomal membrane. Accordingly, dephosphorylation of autophagosomal PI4P prevents the association of STX17 to autophagosomes. Furthermore, molecular dynamics simulations support PI4P-dependent membrane insertion of the transmembrane helices of STX17. Based on these findings, we propose a model in which STX17 recruitment to mature autophagosomes is temporally regulated by a PI4P-driven change in the surface charge of autophagosomes.