bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overcome the Limitation of Phenome-Wide Association Studies (PheWAS): Extension of PheWAS to Efficient and Robust Large-Scale ICD Codes Analysis
Authors: Lin Ya−Chen , Zhang Siwei , Vessels Tess , Bastarache Lisa , Bejan Cosmin Adrian , Hsie Ryan S , Philips Elizabeth J , Ruderfer Doug M , Pulley Jill M. , Edwards Todd L , Wells Quinn S , Warner Jeremy L , Denny Joshua C , Roden Dan M , Kang Hakmook , Xu Yaomin 
Published: April 2024

ABSTRACTThe Phenome-wide association studies (PheWAS) have become widely used for efficient, high-throughput evaluation of relationship between a genetic factor and a large number of disease phenotypes, typically extracted from a DNA biobank linked with electronic medical records (EMR). Phecodes, billing code-derived disease case-control status, are usually used as outcome variables in PheWAS and logistic regression has been the standard choice of analysis method. Since the clinical diagnoses in EMR are often inaccurate with errors which can lead to biases in the odds ratio estimates, much effort has been put to accurately define the cases and controls to ensure an accurate analysis. Specifically in order to correctly classify controls in the population, an exclusion criteria list for each Phecode was manually compiled to obtain unbiased odds ratios. However, the accuracy of the list cannot be guaranteed without extensive data curation process. The costly curation process limits the efficiency of large-scale analyses that take full advantage of all structured phenotypic information available in EMR. Here, we proposed to estimate relative risks (RR) instead. We first demonstrated the desired nature of RR that overcomes the inaccuracy in the controls via theoretical formula. With simulation and real data application, we further confirmed that RR is unbiased without compiling exclusion criteria lists. With RR as estimates, we are able to efficiently extend PheWAS to a larger-scale, phenome construction agnostic analysis of phenotypes, using ICD 9/10 codes, which preserve much more disease-related clinical information than Phecodes.
Enhancing Prosthetic Vision by Upgrade of a Subretinal Photovoltaic Implant in situ
Authors: Bhuckory Mohajeet B. , Monkongpitukkul Nicharee , Shin Andrew , Goldstein Anna Kochnev , Jensen Nathan , Shah Sarthak V , Pham-Howard Davis , Butt Emma , Dalal Roopa , Galambos Ludwig , Mathieson Keith , Kamins Theodore , Palanker Daniel 
Published: April 2024

AbstractIn patients with atrophic age-related macular degeneration, subretinal photovoltaic implant (PRIMA) provided visual acuity up to 20/440, matching its 100μm pixels size. Next-generation implants with smaller pixels should significantly improve the acuity. This study in rats evaluates removal of a subretinal implant, replacement with a newer device, and the resulting grating acuity in-vivo. Six weeks after the initial implantation with planar and 3-dimensional devices, the retina was re-detached, and the devices were successfully removed. Histology demonstrated a preserved inner nuclear layer. Re-implantation of new devices into the same location demonstrated retinal re-attachment to a new implant. New devices with 22μm pixels increased the grating acuity from the 100μm capability of PRIMA implants to 28μm, reaching the limit of natural resolution in rats. Reimplanted devices exhibited the same stimulation threshold as for the first implantation of the same implants in a control group. This study demonstrates the feasibility of safely upgrading the subretinal photovoltaic implants to improve prosthetic visual acuity.
Molecular fingerprints of cell size sensing and mating type differentiation in pennate diatoms
Authors: Belišová Darja , Bilcke Gust , Audoor Sien , D’hondt Sofie , De Veylder Lieven , Vandepoele Klaas , Vyverman Wim 
Published: April 2024

SummaryA unique cell size sensing mechanism is at the heart of the life cycle of diatoms. During population growth, cell size decreases until a Sexual Size Threshold (SST) is reached, below which cells become sexually competent. In most pennate diatoms, the two mating types undergo biochemical and behavioral differentiation below the SST, although the molecular pathways underlying their size-dependent maturation remain unknown.Here, we developed a method to shorten the generation time ofCylindrotheca closteriumthrough single-cell microsurgery, enabling the transcriptomic comparison of genetically identical large and undifferentiated cells with small, sexually competent cells for six different genotypes.We identified 21 genes upregulated in small cells regardless of their mating type, revealing how cells undergo specific transcriptional reprogramming when passing the SST. Furthermore, we revealed a size-regulated gene cluster with three mating type-specific genes susceptible to sex-inducing pheromones. In addition, comparative transcriptomics confirmed the shared mating type specificity of Mating-type Related Minus 2 homologs in three pennate diatoms, suggesting them to be part of a conserved partner-recognition mechanism.This study sheds light on how diatoms acquire sexual competence in a strictly size-dependent manner, revealing a complex machinery underlying size-dependent maturation, mating behavior, and heterothally in pennate diatoms.
Homeostats – the hidden rulers of ion homeostasis in plants
Authors: Dreyer Ingo , Hernández-Rojas Naomí , Bolua-Hernández Yasnaya , de los Angeles Tapia-Castillo Valentina , Astola-Mariscal Sadith Zobeida , Díaz-Pico Erbio , Mérida-Quesada Franko , Vergara-Valladares Fernando , Arrey-Salas Oscar , Rubio-Meléndez María Eugenia , Riedelsberger Janin , Michard Erwan 
Published: April 2024

AbstractIon homeostasis is a crucial process in plants that is closely linked to the efficiency of nutrient uptake, stress tolerance and overall plant growth and development. Nevertheless, our understanding of the fundamental processes of ion homeostasis is still incomplete and highly fragmented. Especially at the mechanistic level, we are still in the process of dissecting physiological systems to analyze the different parts in isolation. However, modeling approaches have shown that it is not individual transporters but rather transporter networks (homeostats) that control membrane transport and associated homeostatic processes in plant cells. To facilitate access to such theoretical approaches, the modeling of the potassium homeostat is explained here in detail to serve as a blueprint for other homeostats. Based on a few, elementary knowledge about the thermodynamics of the different transport processes, it is possible to draw fundamental conclusions about the properties and physiology of the transporter network.
Systems Neuroscience Computing in Python (SyNCoPy): A Python Package for Large-scale Analysis of Electrophysiological Data
Authors: Mönke Gregor , Schäfer Tim , Parto-Dezfouli Mohsen , Kajal Diljit Singh , Fürtinger Stefan , Schmiedt Joscha Tapani , Fries Pascal 
Published: April 2024

AbstractWe introduce an open-source Python package for the analysis of large-scale electrophysiological data called SyNCoPy, for Systems Neuroscience Computing in Python. The package includes signal processing analyses across time (e.g. time-lock analysis), frequency (e.g. power spectrum), and connectivity (e.g. coherence) domains. It enables user-friendly data analysis on both laptop-based and high-performance computing systems. SyNCoPy is designed to facilitate trial-parallel workflows (parallel processing of trials) making it an ideal tool for large-scale analysis of electrophysiological data. Based on parallel processing of trials, the software can support very large-scale datasets via innovative out-of-core computation techniques. It also provides seamless interoperability with other standard software packages through a range of file format importers and exporters and open file formats. The naming of the user functions closely follows the well-established FieldTrip framework, which is an open-source Matlab toolbox for advanced analysis of electrophysiological data.
EcoHIV Infection Modulates the Effects of Cocaine Exposure Pattern and Abstinence on Cocaine Seeking and Neuroimmune Protein Expression in Male Mice
Authors: Namba Mark D. , Xie Qiaowei , Park Kyewon , Jackson Joshua G. , Barker Jacqueline M. 
Published: April 2024

AbstractCocaine use disorders (CUDs) and human immunodeficiency virus (HIV) remain persistent public health dilemmas throughout the world. One major hurdle for treating CUD is the increase in cocaine craving and seeking behavior that occurs over a protracted period of abstinence, an effect known as the incubation of craving. Little is known about how HIV may modulate this process. Thus, we sought to examine the impact of chronic HIV infection on the incubation of cocaine craving and associated changes in the central and peripheral immune systems. Here, mice were inoculated with EcoHIV, which is a chimeric HIV-1 construct that produces chronic HIV infection in mice. EcoHIV- and sham- infected mice were conditioned with cocaine daily or intermittently in a conditioned place preference (CPP) paradigm, followed by 1 or 21 days of forced abstinence prior to assessing preference for the cocaine-paired chamber. Under both conditioning regimens, sham mice exhibited incubation of cocaine CPP after 21 days of abstinence. EcoHIV- infected mice conditioned daily with cocaine showed enhanced cocaine seeking at both abstinence timepoints, whereas infected mice conditioned intermittently showed a reversal of the incubation effect, with higher cocaine seeking after 1 day of abstinence compared to 21 days. Analysis of corticolimbic CX3CL1-CX3CR1 and glutamate receptor expression revealed alterations in medial prefrontal cortex (mPFC) CX3CL1 and nucleus accumbens (NAc) GluN2A receptors that correlated with cocaine seeking following daily cocaine exposure. Moreover, examination of peripheral immune markers showed that the effect of abstinence and EcoHIV infection on these measures depended on the cocaine exposure regimen. Altogether, these results highlight the importance of cocaine abstinence and exposure pattern as critical variables that modulate HIV-associated neuroimmune outcomes and relapse vulnerability.
A Status-Neutral Approach to HIV – Is Targeted Testing Still Relevant South of Sahara?
Authors: Mugauri Hamufare , Mugurungi Owen , Chirenda Joconiah , Takarinda Kudakwashe , Mangwiro Prosper , Tshimanga Mufuta 
Published: April 2024

AbstractIntroductionIn 2022, UNAIDS replaced the 90% Global HIV targets with six Comprehensive 95% targets that include linkage to comprehensive HIV prevention services, the thrust of the status-neutral approach to HIV testing. Zimbabwe has been implementing both targeted testing and the status-neutral concept. In this paper, we analyse the role of status-neutral concepts in targeted testing, for effective case identification and linkage to prevention and treatment services.MethodsWe conducted a cross-sectional study on 36 multi-stage sampled sites across 4/10 provinces of Zimbabwe. Screened and non-screened patients were tested and analysed for positivity ratios and linkage to post-test services. Data were extracted using Epicollect5 and imported into EpiData software and Stata for cleaning and analysis. Data were summarized as proportions, odds ratios and adjusted odds ratios at 5% significance level.ResultsOf 23,058 HIV tests done, females constituted 55% (n=12,698), whilst 63.5% (n=14,650) were retests and positivity of 7.5% obtained. Screened patients contributed 75.1% to the overall positivity (1,296/1,727), from 66% (n=15,289) of the total tests conducted. The 45–49-year category was 3.6 times more likely to test positive (a95%CI:2.67,4.90). Males were 3.09 times more likely to test positive in adjusted analysis (a95%CI: 2.74, 3.49), from an 8% (n=912) positivity ratio. First tests were 65% more likely to test HIV positive (a95%CI: 1.43, 1.91) whilst screened patients were 3.89 times more likely to link to HIV prevention services (a95%CI: 3.05, 4.97), against 25.5% (n=1,871) linkage among patients not screenedConclusionTargeted and status-neutral testing are related and complimentary concepts which, when simultaneously applied, potentiates case identification through prioritizing high-risk individuals for testing, as well as arresting ongoing transmission of HIV through effective linkage to HIV prevention and treatment. This approach facilitates economic usage of limited resources, in generalized epidemics.
What role do community-level factors play in HIV self-testing uptake, linkage to services and HIV-related outcomes? A mixed methods study of community-led HIV self-testing programmes in rural Zimbabwe
Authors: Tumushime Mary K , Ruhode Nancy , Neuman Melissa , Watadzaushe Constancia , Mutseta Miriam , Taegtmeyer Miriam , Johnson Cheryl C. , Hatzold Karin , Corbett Elizabeth L. , Cowan Frances M. , Sibanda Euphemia L. 
Published: April 2024

ABSTRACTCommunity-led interventions, where communities plan and lead implementation, are increasingly adopted in public health. We explore what factors may be associated with successful community-led distribution of HIV self-test (HIVST) kits to guide future service delivery.Twenty rural communities were supported to implement month-long HIVST kit distribution programmes from January-September/2019. Participant observation was conducted to document distribution models. Three months post-intervention, a population-based survey measured: self-reported new HIV diagnosis; self-reported HIVST uptake; self-reported linkage to post-test services; and viral load. The survey included questions for a composite measure of ‗community cohesion‘. Communities were grouped into low/medium/high based on community cohesion scores. We used mixed effect logistic regression to assess how outcomes differed by community cohesion. In total, 27,812 kits were distributed by 348 distributors. Two kit distribution models were implemented: door-to-door distribution only or distribution at venues/events within communities. Of 5,683 participants surveyed, 1,831 (32.2%) received kits and 1,229 (67.1%) reported using it; overall HIVST uptake was 1,229/5,683 (21.6%). Self-reported new HIV diagnosis increased with community cohesion, from 32/1,770 (1.8%) in the lowest cohesion group to 40/1,871 (2.1%) in the medium group, adjusted odds ratio (aOR) 2.94 (1.41-6.12, p=0.004) and 66/2,042 (3.2%) in the highest cohesion group, aOR 7.20 (2.31-22.50, p=0.001). Other outcomes did not differ by extent of cohesion.HIVST kit distribution in high-cohesion communities was associated with seven times higher odds of identifying people with new HIV diagnoses, suggesting more cohesive communities may better identify those most at risk of undiagnosed HIV. Communities can learn from and adopt these participatory community-led approaches to intervention planning and implementation, which may foster cohesion and benefit public health programmes.
Improving 10-year cardiovascular risk prediction in patients with type 2 diabetes with metabolomics
Authors: Xie Ruijie , Seum Teresa , Sha Sha , Trares Kira , Holleczek Bernd , Brenner Hermann , Schöttker Ben 
Published: April 2024

AbstractBackground and AimsTo evaluate the potential of improved prediction of the 10-year risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes by adding metabolomic biomarkers to the SCORE2-Diabetes model.MethodsData from 10,257 and 1,039 patients with type 2 diabetes from the UK Biobank (UKB) and the German ESTHER cohort, respectively, were used for model derivation, internal and external validation. A total of 249 metabolites were measured with nuclear magnetic resonance (NMR) spectroscopy. LASSO regression with bootstrapping was used to identify metabolites in sex-specific analyses and the predictive performance of metabolites added to the SCORE2-Diabetes model was primarily evaluated with Harrell’s C-index.ResultsSeven metabolomic biomarkers were selected by LASSO regression for enhanced MACE risk prediction (three for both sexes, three male- and one female-specific metabolite(s)). Especially albumin and the omega-3-fatty-acids-to-total-fatty-acids-percentage among males and lactate among females improved the C-index. In internal validation with 30% of the UKB, adding the selected metabolites to the SCORE2-Diabetes model increased the C-index statistically significantly (P=0.034) from 0.660 to 0.680 in the total sample. In external validation with ESTHER, the C-index increase was higher (+0.041) and remained statistically significant (P=0.015).ConclusionsIncorporating seven metabolomic biomarkers in the SCORE2-Diabetes model enhanced its ability to predict MACE in patients with type 2 diabetes. Given the latest cost reduction and standardization efforts, NMR metabolomics has the potential for translation into the clinical routine.
Fiberscopic Pattern Removal for Optimal Coverage in 3D Bladder Reconstructions of Fiberscope Cystoscopy Videos
Authors: Eimen Rachel , Krzyzanowska Halina , Scarpato Kristen R. , Bowden Audrey K. 
Published: April 2024

AbstractPurposeIn the current clinical standard of care, cystoscopic video is not routinely saved because it is cumbersome to review. Instead, clinicians rely on brief procedure notes and still frames to manage bladder pathology. Preserving discarded data via 3D reconstructions, which are convenient to review, has the potential to improve patient care. However, many clinical videos are collected by fiberscopes, which are lower cost but induce a pattern on frames that inhibits 3D reconstruction. The aim of this study is to remove the honeycomb-like pattern present in fiberscope-based cystoscopy videos to improve the quality of 3D bladder reconstructions.ApproachThis study introduces a novel algorithm that applies a notch filtering mask in the Fourier domain to remove the honeycomb-like pattern from clinical cystoscopy videos collected by fiberscope as a preprocessing step to 3D reconstruction. We produce 3D reconstructions with the video before and after removing the pattern, which we compare with a novel metric termed the area of reconstruction coverage (ARC), defined as the surface area (in pixels) of the reconstructed bladder. All statistical analyses use paired t-tests.ResultsPreprocessing using our method for pattern removal enabled reconstruction for all (n = 5) cystoscopy videos included in the study and produced a statistically significant increase in bladder coverage (p = 0.018).ConclusionsThis algorithm for pattern removal increases bladder coverage in 3D reconstructions and automates mask generation and application, which could aid implementation in time-starved clinical environments. The creation and use of 3D reconstructions can improve documentation of cystoscopic findings for future surgical navigation, thus improving patient treatment and outcomes.
Associations Between Exercise Capacity and Psychological Functioning in Children and Adolescents with Fontan Circulation
Authors: Seivert Nicholas P. , Dodds Kathryn M. , O’Malley Shannon , Goldberg David J. , Paridon Stephen , McBride Michael , Rychik Jack 
Published: April 2024

AbstractBackgroundPediatric patients with Fontan circulation (FC) often have diminished exercise capacity. They are also at risk for psychological problems, including anxiety, depression, and inattention. The current study examines associations between exercise capacity and psychological functioning in a clinical sample of pediatric patients with FC.MethodsA multidisciplinary team evaluated participants in a dedicated clinic for pediatric patients with FC. Patients completed cardiopulmonary exercise testing (CPET); metrics selected for analyses included peak oxygen consumption (VO2), maximum achieved heart rate (HR), oxygen saturation at peak exercise, ventilatory anaerobic threshold, work rate, respiratory exchange ratio, and HR recovery at 1-, 3-, and 8-minutes after exercise. Parent and child were administered a standardized questionnaire to measure depression, anxiety, and inattention symptoms. Patients who completed CPET with adequate effort and a psychological measure were eligible for inclusion. Clinical data were extracted from medical records and analyzed using Pearson correlations.ResultsClinical sample (n = 51) was 55% male with a mean age of 13.6 years (SD=2.5). A majority had hypoplastic left heart syndrome (51%). There was a significant negative correlation between parent-report of inattention and peak VO2 (R= -.307, 95% CI -.549/-.018,P= 0.038). Self-report of anxiety was positively correlated with HR recovery at 3 (R= .438, 95% CI .155/.655,P= 0.004) and 8 (R= .432, 95% CI .147/.651,P= 0.004) minutes post exercise. Depression was positively correlated with HR recovery at 3 minutes for parent report (R= .294, 95% CI .004/.538,P= 0.047) and 8 minutes for self-report (R= .410, 95% CI .122/.635,P= 0.007).ConclusionsInattention, depression, and anxiety symptoms were correlated with some CPET metrics in our clinical sample of pediatric patients with FC. Greater inattention symptoms were associated with lower peak VO2. Those with greater depression and anxiety symptoms showed a more rapid decline from max HR to recovery period.What is KnownMany patients with Fontan circulation (FC) have some degree of diminished exercise capacity.The risk for mental health problems in pediatric patients with FC is very high, with an estimated lifetime prevalence of 65%.What the Study AddsThere may be a link between mental health symptoms and exercise capacity metrics obtained during CPET for children and adolescents with FC.Our study found that greater inattention symptoms were linked to lower observed peak VO2 during CPET.Participants with higher levels of depression and anxiety symptoms exhibited a more dramatic decline in HR after exercise, contrary to findings in other cardiac patient samples that report an attenuated HR response for those with depression and anxiety.