bluuebunny/crossref_metadata_2025_split huggingface dataset:
GWAS of cataract in Puerto Ricans identifies a novel large-effect variant in ITGA6
Authors: Shi Jingchunzi , O’Connell Jared , Hicks Barry , Wang Wei , Bryc Katarzyna , Brady Jennifer J. , Vacic Vladimir , Freyman Will , Abul-Husn Noura S. , Auton Adam ,   23andMe Research Team, Shringarpure Suyash 
Published: July 2023

AbstractCataract is a common cause of vision loss and affects millions of people worldwide. Genome-wide association studies (GWAS) and family studies of cataract have demonstrated a role for genetics in cataract susceptibility. However, most of these studies have been conducted in populations of European or Asian descent, leaving the genetic etiology of cataract among Hispanic/Latino (HL) populations unclear. Here we perform the first GWAS of cataract in a Puerto Rican population of research participants derived from the customer base of 23andMe, Inc. In our analysis with 3,060 self-reported cases and 41,890 controls, we found a novel association of large effect size with a rare coding variant in the ITGA6 gene (rs200560853, p-value=2.9×10−12, OR=12.7, 95% CI=[6.5, 24.7]). ITGA6 is part of the integrin alpha chain in the laminin receptor subfamily, and likely contributes to eye lens homeostasis, transparency, and cell survival. We found that this coding variant is associated with a 13.7 year earlier disease onset on average, as well as a 4.3-fold higher rate of cataract events in the Puerto Rican population. The variant has a minor allele frequency (MAF) of 0.089% in Puerto Rico and is extremely rare elsewhere in the world. Population genetic analyses showed that the variant is only found in individuals with ancestry from the Americas and countries bordering the Mediterranean Sea, suggesting a North African origin. Our discovery identifies a novel genetic risk factor for cataract in Puerto Ricans and highlights the importance of including underrepresented populations in genomics research to improve our understanding of disease in all populations.
Wagers for work: Decomposing the costs of cognitive effort
Authors: Master Sarah L. , Curtis Clayton E. , Dayan Peter 
Published: July 2023

AbstractSome aspects of cognition are more taxing than others. Accordingly, many people will avoid cognitively demanding tasks in favor of simpler alternatives. Which components of these tasks are costly, and how much, remains unknown. Here, we use a novel task design in which subjects request wages for completing cognitive tasks and a computational modeling procedure that decomposes their wages into the costs driving them. Using working memory as a test case, our approach revealed that gating new information into memory and protecting against interference are costly. Critically, other factors, like memory load, appeared less costly. Other key factors which may drive effort costs, such as error avoidance, had minimal influence on wage requests. Our approach is sensitive to individual differences, and could be used in psychiatric populations to understand the true underlying nature of apparent cognitive deficits.Author SummaryAnyone who has tried to mentally calculate how much to tip at a restaurant knows that cognitive effort can feel aversive. Doing math in your head, like most high-level cognitive abilities, depends critically on working memory (WM). We know that WM is sometimes effortful to use, but we don’t know which aspects of WM use drive these effort costs. To address this question, we had participants request wages in exchange for performing various tasks that differed in their specific WM demands. Using computational models of their wage demands, we demonstrated that some aspects of WM are costly, such as bringing new information into memory and preventing interference. Other factors, like the amount of information in memory and attempts to avoid mistakes, were less costly. Our approach identified which specific subcomponents of WM are aversive. Future research could use these methods to test theories about how motivational problems might be masquerading as cognitive deficits in psychiatric populations.
Autologous iPSC- and MSC-derived Chondrocyte Implants for Cartilage Repair in a Miniature Pig Model
Authors: Lee Ming-Song , Sivapatham Athillesh , Leiferman Ellen M. , Jiao Hongli , Lu Yan , Nemke Brett W. , Leiferman Matthew , Markel Mark D. , Li Wan-Ju 
Published: July 2023

AbstractInduced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) have greater potential for generating chondrocytes without hypertrophic and fibrotic phenotypes compared to bone marrow-derived mesenchymal stem/stromal cells (BMSCs). However, there is a lack of research demonstrating the use of autologous iMSCs for repairing articular chondral lesions in large animal models. In this study, we aimed to evaluate the effectiveness of autologous miniature pig (minipig) iMSC-chondrocyte (iMSC-Ch)-laden implants in comparison to autologous BMSC-chondrocyte (BMSC-Ch)-laden implants for cartilage repair in porcine femoral condyles. iMSCs and BMSCs were seeded into fibrin glue/nanofiber constructs and cultured with chondrogenic induction media for 7 days before implantation. To assess the regenerative capacity of the cells, 19 skeletally mature Yucatan minipigs were randomly divided into microfracture control, acellular scaffold, iMSC, and BMSC subgroups. A cylindrical defect measuring 7 mm in diameter and 0.6 mm in depth was created on the articular cartilage surface without violating the subchondral bone. The defects were then left untreated or treated with acellular or cellular implants. Both cellular implant-treated groups exhibited enhanced joint repair compared to the microfracture and acellular control groups. Immunofluorescence analysis yielded significant findings, showing that cartilage treated with iMSC-Ch implants exhibited higher expression of COL2A1 and minimal to no expression of COL1A1 and COL10A1, in contrast to the BMSC-Ch-treated group. This indicates that the iMSC-Ch implants generated more hyaline cartilage-like tissue compared to the BMSC-Ch implants. These results contribute to filling the knowledge gap regarding the potential of autologous iPSC derivatives for cartilage repair in translational animal models.
Parallel EEG assessment of different sound predictability levels in tinnitus
Authors: Brinkmann Pia , Devos Jana V. P. , van der Eerden Jelle H. M. , Smit Jasper V. , Janssen Marcus L. F. , Kotz Sonja A. , Schwartze Michael 
Published: July 2023

AbstractObjectiveTinnitus denotes perception of a non-environmental sound and might result from aberrant auditory prediction. Successful prediction of formal (e.g. type) and temporal sound characteristics facilitates the filtering of irrelevant information (“sensory gating”, SG). Here, we explored if and how parallel manipulations of formal and temporal predictability affect sensory gating in persons with and without tinnitus.MethodsAge-, education- and sex-matched persons with and without tinnitus (N = 52) participated and listened to paired-tone “oddball” sequences, varying in formal (standard vs. deviant pitch) and temporal predictability (isochronous vs. random timing). EEG was recorded from 128 channels and data were analyzed by means of temporal spatial principal component analysis (tsPCA).ResultsSG was observed in P50- and N100-like activity (amplitude suppression for the 2ndtone in the pair) in both timing conditions and groups. Correspondingly, deviants elicited overall larger amplitudes than standards. However, only in persons without tinnitus N100-like activity in response to deviants was enhanced with isochronous relative to random timing.ConclusionsPersons with tinnitus do not benefit similarly as persons without tinnitus from temporally predictable context in deviance processing.SignificanceThe current results indicate altered temporal sensitivity and selective attention allocation in persons with tinnitus.Highlights-Persons with tinnitus display altered auditory predictions affecting the processing of unexpected auditory input-Position predictions did not differ between persons with tinnitus and without-Temporal predictability facilitated deviance processing for P50-like activity in persons with tinnitus and without
Dynamic local mRNA distribution and translation influence the postnatal molecular maturation of perivascular astrocytic processes
Authors: Avila-Gutierrez Katia , Slaoui Leila , Alvear Rodrigo , Kozlowski Esther , Oudart Marc , Augustin Emma , Mailly Philippe , Monnet Héloïse , Mignon Virginie , Saubaméa Bruno , Boulay Anne-Cécile , Cohen-Salmon Martine 
Published: July 2023

AbstractAstrocytes (the main glial cells in the brain) are highly ramified and send out perivascular processes (PvAPs) that entirely sheathe the brain’s blood vessels. PvAPs are equipped with an enriched molecular repertoire that sustains astrocytic regulatory functions at the vascular interface. In the mouse, PvAP development starts after birth and is essentially complete by postnatal day (P) 15. Progressive molecular maturation also occurs over this period, with the acquisition of proteins enriched in PvAPs. The mechanisms controlling the development and molecular maturation of PvAPs have not been extensively characterized. We reported previously that mRNAs are distributed unequally in mature PvAPs and are locally translated. Since dynamic mRNA distribution and local translation influence the cell’s polarity, we hypothesized that they might sustain the postnatal maturation of PvAPs. Here, we used a combination of molecular biology and imaging approaches to demonstrate that the development of PvAPs is accompanied by the transport of mRNA and polysomal mRNA into PvAPs, the development of a rough endoplasmic reticulum (RER) network and Golgi cisternae, and local translation. By focusing on genes and proteins that are selectively or specifically expressed in astrocytes, we characterized the developmental profile of mRNAs, polysomal mRNAs and proteins in PvAPs from P5 to P60. Furthermore, we found that distribution of mRNAs in PvAPs is perturbed in a mouse model of megalencephalic leukoencephalopathy with subcortical cysts. Lastly, we found that some polysomal mRNAs polarized progressively towards the PvAPs. Our results indicate that dynamic mRNA distribution and local translation influence the postnatal maturation of PvAPs.Summary statementLocal translation operates during the postnatal development of perivascular astrocyte processes and might contribute to their molecular maturation.
Rastermap: a discovery method for neural population recordings
Authors: Stringer Carsen , Zhong Lin , Syeda Atika , Du Fengtong , Kesa Maria , Pachitariu Marius 
Published: July 2023

AbstractNeurophysiology has long progressed through exploratory experiments and chance discoveries. Anecdotes abound of researchers setting up experiments while listening to spikes in real time and observing a pattern of consistent firing when certain stimuli or behaviors happened. With the advent of large-scale recordings, such close observation of data has become harder because high-dimensional spaces are impenetrable to our pattern-finding intuitions. To help ourselves find patterns in neural data, our lab has been openly developing a visualization framework known as “Rastermap” over the past five years. Rastermap takes advantage of a new global optimization algorithm for sorting neural responses along a one-dimensional manifold. Displayed as a raster plot, the sorted neurons show a variety of activity patterns, which can be more easily identified and interpreted. We first benchmark Rastermap on realistic simulations with multiplexed cognitive variables. Then we demonstrate it on recordings of tens of thousands of neurons from mouse visual and sensorimotor cortex during spontaneous, stimulus-evoked and task-evoked epochs, as well as on whole-brain zebrafish recordings, widefield calcium imaging data, population recordings from rat hippocampus and artificial neural networks. Finally, we illustrate high-dimensional scenarios where Rastermap and similar algorithms cannot be used effectively.
Systematic assessment of long-read RNA-seq methods for transcript identification and quantification
Authors: Pardo-Palacios Francisco J. , Wang Dingjie , Reese Fairlie , Diekhans Mark , Carbonell-Sala Sílvia , Williams Brian , Loveland Jane E. , De María Maite , Adams Matthew S. , Balderrama-Gutierrez Gabriela , Behera Amit K. , Gonzalez Jose M. , Hunt Toby , Lagarde Julien , Liang Cindy E. , Li Haoran , Meade Marcus Jerryd , Amador David A. Moraga , Prjibelski Andrey D. , Birol Inanc , Bostan Hamed , Brooks Ashley M. , Çelik Muhammed Hasan , Chen Ying , Du Mei R.M. , Felton Colette , Göke Jonathan , Hafezqorani Saber , Herwig Ralf , Kawaji Hideya , Lee Joseph , Li Jian-Liang , Lienhard Matthias , Mikheenko Alla , Mulligan Dennis , Nip Ka Ming , Pertea Mihaela , Ritchie Matthew E. , Sim Andre D. , Tang Alison D. , Wan Yuk Kei , Wang Changqing , Wong Brandon Y. , Yang Chen , Barnes If , Berry Andrew , Capella Salvador , Dhillon Namrita , Fernandez-Gonzalez Jose M. , Ferrández-Peral Luis , Garcia-Reyero Natàlia , Goetz Stefan , Hernández-Ferrer Carles , Kondratova Liudmyla , Liu Tianyuan , Martinez-Martin Alessandra , Menor Carlos , Mestre-Tomás Jorge , Mudge Jonathan M. , Panayotova Nedka G. , Paniagua Alejandro , Repchevsky Dmitry , Rouchka Eric , Saint-John Brandon , Sapena Enrique , Sheynkman Leon , Smith Melissa Laird , Suner Marie-Marthe , Takahashi Hazuki , Youngworth Ingrid Ashley , Carninci Piero , Denslow Nancy D. , Guigó Roderic , Hunter Margaret E. , Tilgner Hagen U. , Wold Barbara J. , Vollmers Christopher , Frankish Adam , Au Kin Fai , Sheynkman Gloria M. , Mortazavi Ali , Conesa Ana , Brooks Angela N. 
Published: July 2023

AbstractThe Long-read RNA-Seq Genome Annotation Assessment Project (LRGASP) Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. The consortium generated over 427 million long-read sequences from cDNA and direct RNA datasets, encompassing human, mouse, and manatee species, using different protocols and sequencing platforms. These data were utilized by developers to address challenges in transcript isoform detection and quantification, as well asde novotranscript isoform identification. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. When aiming to detect rare and novel transcripts or when using reference-free approaches, incorporating additional orthogonal data and replicate samples are advised. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis.
Management of splenic injury in children and young adults: a survey of surgeons investigating factors responsible for variations in care using the Theoretical Domains Framework
Authors: Adams Susan E , Holland Andrew JA , Brown Julie 
Published: July 2023

STRUCTURED ABSTRACTObjective: To identify differences in practice and behavioural drivers in adult and paediatric surgeons related to the management of splenic injury in children and young people.Background: Despite the existence of guidelines, there are variations in the care of children with splenic injuries. There are no specific guidelines for the care of young adults, who may be managed according to either paediatric or adult practices. The drivers of variation in trauma management between adult and paediatric surgeons have not been examined through an implementation science lens.Methods: The COM-B model of behaviour and theoretical domains framework were used to construct a survey which was delivered to a cross-section of adult general surgeons and paediatric surgeons working in public hospitals throughout NSW, Australia. The capability, opportunity, and motivation for management decisions were analysed. Outcome variables were compared between the practitioner groups. Statistical significance was set at p < 0.05.Results: Eighty (26.4%) responses met the inclusion criteria. Significant differences between adult and paediatric surgeons were identified in terms of: capability (surgeon training and experience); opportunity (hospital, personnel, and resources); and motivation (comfort with splenic injury care at different ages). In managing splenic injury, pediatric surgeons tended to follow pediatric guidelines while adult surgeons followed adult guidelines, making some adjustments for age. All agreed guidelines had the potential to improve care.Conclusions: This study identified several behavioural drivers for observed variations in the care of splenic injury in children and young adults. The results indicate that contextually relevant guidelines for managing splenic injury in children and young people across any setting may be needed to reduce disparities in care. These should be underpinned by interventions designed to further address the drivers of surgeon behaviour to optimise uptake. Furthermore, splenic injury care is a clinical indicator of the quality of trauma care more broadly. Addressing variation in its care has the potential to translate to other trauma system improvements.HIGHLIGHTSUnwarranted variations in splenic injury management have been reported.This is the first examination of surgeon behaviour in the provision of trauma care through an implementation science lens.Differences in the capability, opportunity, and motivation of surgeons in providing evidence-based care to children and young adults with splenic injury were found.Contextually relevant guidelines, underpinned by supporting interventions addressing these behavioural drivers, are needed to reduce disparities in care.
The Eye-image Features of Patients with Coronary Heart Disease Assed: A prospective, observational study of traditional Chinese medicine combined with modern medicine
Authors: Gao Zhanqun , Zhang Dirui , Weng Ziqian , Liu Minghao , Gao Yubo , Hao Wei , Zhao Chen , Zeng Ming , Feng Xue , Wang Shengfang , Yi Boling , Xie Chunqi , Qin Yuhan , He Luping , Xu Yishuo , Jia Haibo , Fang Chao , Zhang Zhi , Hu Sining , Yu Bo 
Published: July 2023

AbstractBACKGROUNDCoronary heart disease (CHD) significantly impacts human health. Traditional Chinese medicine (TCM) suggests a possible correlation between eye-image and CHD, but this relationship has not been fully explored in Western medicine.PURPOSEWe aim to investigate the potential causal relationship between eye-image features and CHD, as examined by coronary angiography (CAG).METHODSThe study selected patients hospitalized in the Department of Cardiology from November 15, 2021, to February 27, 2022. The selected patients were divided into two groups based on their CAG findings: the CHD group (at least one coronary lesion stenosis≥ 50%) and the control group (lesion stenosis<50%)RESURTSThe final analysis included 342 patients out of a total of 426 participants, of these, 165 patients (48.2%) were diagnosed with CHD. The study found that certain characteristics in the left region 5(L5) and right region ( R5) were associated with CHD, including L5 pink dark speckle (OR: 4.143, 95%CI: 1.135-15.124,P=0.031), L5 vascular tortuosity (OR: 0.234, 95%CI: 0.077-0.71,P=0.010) R5 dark red blood vessels (known as Xue mai in TCM) (OR: 1.683, 95%CI: 1.035-2.738,P=0.036), and R5 yellowish mounds (OR: 2.083, 95%CI: 1.221-3.554,P= 0.007). Multivariate regression analyses showed that L5 vascular tortuosity had a negative correlation with CHD.CONCLUSIONOur study revealed that four types of eye-image features, namely pink dark speckle, vascular tortuosity, dark red blood vessels, and yellowish mounds are associated with CHD. Among these features, vascular tortuosity showed a negative correlation with CHD, which could potentially aid in the diagnosis of the disease.
Ribosomal Protein SA (RPSA) is required for localized translation and sarcomere maintenance in mice
Authors: Haddad Rami , Sadeh Omer , Ziv Tamar , Erlich Itai , Haimovich-Caspi Lilac , Shemesh Ariel , van der Velden Jolanda , Kehat Izhak 
Published: July 2023

AbstractCardiomyocyte sarcomeres contain localized ribosomes, but the factors responsible for their localization and the significance of localized translation are unknown. Using proximity labeling, we identified Ribosomal Protein SA (RPSA) as a Z-line protein. In cultured cardiomyocytes, the loss of RPSA led to impaired local protein translation and reduced sarcomere integrity. By employing CAS9 expressing mice along with adeno-associated viruses expressing CRE recombinase and single-guide RNAs targetingRpsa, we knocked outRpsain vivo and observed mis-localization of ribosomes and diminished local translation. These genetic mosaic mice withRpsaknockout in a subset of cardiomyocytes developed dilated cardiomyopathy, featuring atrophy of RPSA-deficient cardiomyocytes, compensatory hypertrophy of unaffected cardiomyocytes, left ventricular dilation, and impaired contractile function. We demonstrate that RPSA C-terminal domain is sufficient for localization to the Z-lines and that if the microtubule network is disrupted RPSA loses its sarcomeric localization. These findings highlight RPSA as a ribosomal factor essential for ribosome localization to the Z-line, facilitating local translation and sarcomere maintenance.
A distributed brain response predicting the facial expression of acute nociceptive pain
Authors: Picard Marie-Eve , Kunz Miriam , Chen Jen-I , Coll Michel-Pierre , Vachon-Presseau Étienne , Wager Tor D. , Rainville Pierre 
Published: July 2023

AbstractPain is a private experience observable through various verbal and non-verbal behavioural manifestations, each of which may relate to different pain-related functions. Despite the importance of understanding the cerebral mechanisms underlying those manifestations, there is currently limited knowledge on the neural correlates of the facial expression of pain. In this functional magnetic resonance imaging (fMRI) study, noxious heat stimulation was applied in healthy volunteers and we tested if previously published brain signatures of pain were sensitive to pain expression. We then applied a multivariate pattern analysis to the fMRI data to predict the facial expression of pain. Results revealed the inability of previously developed pain neurosignatures to predict the facial expression of pain. We thus propose a Facial Expression of Pain Signature (FEPS) conveying distinctive information about the brain response to nociceptive stimulations with minimal or no overlap with other pain-relevant brain signatures associated with nociception, pain ratings, thermal pain aversiveness, or pain valuation. The FEPS may provide a distinctive functional characterization of the distributed cerebral response to nociceptive pain associated with the socio-communicative role of non-verbal pain expression. This underscores the complexity of pain phenomenology by reinforcing the view that neurosignatures conceived as biomarkers must be interpreted in relation to the specific pain manifestation(s) predicted and their underlying function(s). Future studies should explore other pain-relevant manifestations and assess the specificity of the FEPS against simulated pain expressions and other types of aversive or emotional states.