bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prebiotic diet changes neural correlates of food decision-making in overweight adults: a randomized controlled within-subject cross-over trial
Authors: Medawar Evelyn , Beyer Frauke , Thieleking Ronja , Haange Sven-Bastiaan , Rolle-Kampczyk Ulrike , Reinicke Madlen , Chakaroun Rima , von Bergen Martin , Stumvoll Michael , Villringer Arno , Witte A. Veronica 
Published: June 2023

AbstractObjectiveAnimal studies suggest that prebiotic, plant-derived nutrients could improve homeostatic and hedonic brain functions through improvements in microbiome-gut-brain communication. However, little is known if these results are applicable to humans. Therefore, we tested the effects of high-dosed prebiotic fiber on reward-related food decision-making in a randomized controlled within-subject cross-over study and assayed potential microbial and metabolic markers.Design59 overweight young adults (19 females, 18-42 years, body mass index 25-30 kg/m2) underwent functional task MRI before and after 14 days of supplementary intake of 30 g/d of inulin (prebiotics) and equicaloric placebo, respectively. Short chain fatty acids (SCFA), gastrointestinal hormones, glucose/lipid and inflammatory markers were assayed in fasting blood. Gut microbiota and SCFA were measured in stool.ResultsCompared to placebo, participants showed decreased brain activation towards high-caloric wanted food stimuli in the ventral tegmental area and right orbitofrontal cortex after prebiotics (pre-registered, pFWE < 0.05). While fasting blood levels remained largely unchanged, 16S-rRNA sequencing showed significant shifts in the microbiome towards increased occurrence of, among others, SCFA-producingBifidobacteriacea, and changes in >90 predicted functional signaling pathways after prebiotic intake. Changes in brain activation correlated with changes inActinobacteriamicrobial abundance and associated activity linked with SCFA production, such as ABC transporter metabolism.ConclusionsIn this proof-of-concept study, a prebiotic intervention attenuated reward-related brain activation during food-decision making, paralleled by shifts in gut microbiota indicative of higher SCFA production.
A review of behavioural rating scales for the assessment of Attention Deficit/Hyperactivity Disorder among adults in research
Authors: Grandjean Marius , Hochman Shachar , Mukherjee Raja , Cohen Kadosh Roi 
Published: June 2023

AbstractObjectiveThis review aims to provide researchers with a contemporary and comprehensive understanding of the current state of behavioural rating scales used in evaluating adult ADHD for research purposes. The objective is to offer guidance that enables researchers to make informed decisions when selecting the most suitable scale for their studies. Moreover, our intention was to map and compare these scales, with a specific focus on detecting feigned or invalid symptom presentation—an aspect notably overlooked in prior reviews.MethodWe reviewed the most recent literature on behavioural rating scales for adult ADHD assessment. We evaluated the scales and compared them based on their psychometric properties and the range of symptoms that they assessed.ResultsThe Conners’ Adult ADHD Rating Scales (CAARS), Mind Excessively Wandering Scale (MEWS), and Wender Utah Rating Scale (WURS) have emerged as the most accurate measures for assessing adult ADHD. Moreover, there is an increasing emphasis on the development of assessment tools, either integrated within existing scales or as independent measures, to evaluate feigning or invalid symptom presentation. In that regard, stand-alone measures have demonstrated greater effectiveness compared to embedded measures, with the ADHD Symptom Infrequency Scale (ASIS) being identified as the most accurate scale for the detection of feigning.ConclusionBased on this review, we provide recommendations for the behavioural rating scales with the most accurate measurement of relevant variables in research-related settings.
A non-enzymatic test for SARS-CoV-2 RNA using DNA nanoswitches
Authors: Vilcapoma Javier , Aliyeva Asmer , Hayden Andrew , Chandrasekaran Arun Richard , Zhou Lifeng , Abraham Punnoose Jibin , Yang Darren , Hansen Clinton , Shiu Simon Chi-Chin , Russell Alexis , George Kirsten St. , Wong Wesley P. , Halvorsen Ken 
Published: June 2023

AbstractThe emergence of a highly contagious novel coronavirus in 2019 led to an unprecedented need for large scale diagnostic testing. The associated challenges including reagent shortages, cost, deployment delays, and turnaround time have all highlighted the need for an alternative suite of low-cost tests. Here, we demonstrate a diagnostic test for SARS-CoV-2 RNA that provides direct detection of viral RNA and eliminates the need for costly enzymes. We employ DNA nanoswitches that respond to segments of the viral RNA by a change in shape that is readable by gel electrophoresis. A new multi-targeting approach samples 120 different viral regions to improve the limit of detection and provide robust detection of viral variants. We apply our approach to a cohort of clinical samples, positively identifying a subset of samples with high viral loads. Since our method directly detects multiple regions of viral RNA without amplification, it eliminates the risk of amplicon contamination and renders the method less susceptible to false positives. This new tool can benefit the COVID-19 pandemic and future emerging outbreaks, providing a third option between amplification-based RNA detection and protein antigen detection. Ultimately, we believe this tool can be adapted both for low-resource onsite testing as well as for monitoring viral loads in recovering patients.
Role of endogenous adenine in kidney failure and mortality with diabetes
Authors: Sharma Kumar , Zhang Guanshi , Hansen Jens , Bjornstad Petter , Lee Hak Joo , Menon Rajasree , Hejazi Leila , Liu Jian-Jun , Franzone Anthony , Looker Helen C. , Choi Byeong Yeob , Fernandez Roman , Venkatachalam Manjeri A. , Kugathasan Luxcia , Sridhar Vikas S. , Natarajan Loki , Zhang Jing , Sharma Varun , Kwan Brian , Waikar Sushrut , Himmelfarb Jonathan , Tuttle Katherine , Kestenbaum Bryan , Fuhrer Tobias , Feldman Harold , de Boer Ian H. , Tucci Fabio C. , Sedor John , Heerspink Hiddo Lambers , Schaub Jennifer , Otto Edgar , Hodgin Jeffrey B. , Kretzler Matthias , Anderton Christopher , Alexandrov Theodore , Cherney David , Lim Su Chi , Nelson Robert G. , Gelfond Jonathan , Iyengar Ravi ,   the Kidney Precision Medicine Project
Published: June 2023

AbstractDiabetic kidney disease (DKD) can lead to end-stage kidney disease (ESKD) and mortality, however, few mechanistic biomarkers are available for high risk patients, especially those without macroalbuminuria. Urine from participants with diabetes from Chronic Renal Insufficiency Cohort (CRIC), Singapore Study of Macro-Angiopathy and Reactivity in Type 2 Diabetes (SMART2D), and the Pima Indian Study determined if urine adenine/creatinine ratio (UAdCR) could be a mechanistic biomarker for ESKD. ESKD and mortality were associated with the highest UAdCR tertile in CRIC (HR 1.57, 1.18, 2.10) and SMART2D (HR 1.77, 1.00, 3.12). ESKD was associated with the highest UAdCR tertile in patients without macroalbuminuria in CRIC (HR 2.36, 1.26, 4.39), SMART2D (HR 2.39, 1.08, 5.29), and Pima Indian study (HR 4.57, CI 1.37-13.34). Empagliflozin lowered UAdCR in non-macroalbuminuric participants. Spatial metabolomics localized adenine to kidney pathology and transcriptomics identified ribonucleoprotein biogenesis as a top pathway in proximal tubules of patients without macroalbuminuria, implicating mammalian target of rapamycin (mTOR). Adenine stimulated matrix in tubular cells via mTOR and stimulated mTOR in mouse kidneys. A specific inhibitor of adenine production was found to reduce kidney hypertrophy and kidney injury in diabetic mice. We propose that endogenous adenine may be a causative factor in DKD.
No evidence for differential saccadic adaptation in children and adults with an Autism Spectrum diagnosis
Authors: Tarrit Katy , Freedman Edward G. , Francisco Ana Alves , Horsthuis Douwe J. , Molholm Sophie , Foxe John J. 
Published: June 2023

ABSTRACTBackgroundAltered patterns of eye-movements during scene exploration, and atypical gaze preferences in social settings, have long been noted as features of the Autism phenotype. While these are typically attributed to differences in social engagement and interests (e.g., preferences for inanimate objects over face stimuli), there are also reports of differential saccade measures to non-social stimuli, raising the possibility that fundamental differences in visuo-sensorimotor processing may be at play. Here, we tested the plasticity of the eye-movement system using a classic saccade-adaptation paradigm to assess whether individuals with ASD make typical adjustments to their eye-movements in response to experimentally introduced errors. Saccade adaptation can be measured in infants as young as 10 months, raising the possibility that such measures could be useful as early neuromarkers of ASD risk.MethodsSaccade amplitudes were measured while children and adults with ASD (N=41) and age-matched typically developing (TD) individuals (N=68) made rapid eye-movements to peripherally presented targets. During adaptation trials, the target was relocated from 20-degrees to 15-degrees from fixation once a saccade to the original target location was initiated, a manipulation that leads to systematic reduction in saccade amplitudes in typical observers.ResultsNeither children nor adults with ASD showed any differences relative to TD peers in their abilities to appropriately adapt saccades in the face of persistently introduced errors.ConclusionsOf the three studies to date of saccade adaptation in ASD, none have shown frank deficits in saccade adaptation. Unlike prior studies, we found no evidence for a slower adaptation rate during the early adaptation phase, and no of evidence greater variance of saccade amplitudes in ASD. In post-hoc analysis, there was evidence for larger primary saccades to non-adapted targets, a finding requiring replication in future work.
Potential role of fructose on human colon DNA methylation in racial disparities observed for colorectal cancer risk
Authors: Devall Matthew A. , Eaton Stephen , Hu Gaizun , Sun Xiangqing , Jakum Ethan , Venkatesh Samyukta , Powell Steven M. , Yoshida Cynthia , Weisenberger Daniel J. , Cooper Gregory S. , Willis Joseph , Ebrahim Seham , Zoellner Jamie , Casey Graham , Li Li 
Published: June 2023

AbstractBackground and aimsAn increasing body of observational studies has linked fructose intake to colorectal cancer (CRC). African Americans (AAs) are significantly more likely than European Americans to consume greater quantities of fructose and to develop right-side colon cancer. Yet, a mechanistic link between these two associations remains poorly defined. We aimed to identify differentially methylated regions (DMRs) associated with dietary fructose consumption measures obtained from food frequency questionnaires in a cohort of normal colon biopsies derived from AA men and women (n=79)MethodsDNA methylation data from this study was obtained using the Illumina Infinium MethylationEPIC kit and is housed under accession GSE151732. DMR analysis was carried out usingDMRcatein right and matched left colon, separately. Secondary analysis of CRC tumors was carried out using data derived from TCGA-COAD, GSE101764 and GSE193535. Differential expression analysis was carried out on CRC tumors from TCGA-COAD usingDESeq2.ResultsWe identified 4,263 right-side fructose-DMRs. In contrast, only 24 DMRs survived multiple testing corrections (FDR<0.05) in matched, left colon. To identify targets by which dietary fructose drives CRC risk, we overlaid these findings with data from three CRC tumor datasets. Remarkably, almost 50% of right-side fructose-DMRs overlapped regions associated with CRC in at least one of three datasets.TNXBandCDX2ranked among the most significant fructose risk DMRs in right and left colon respectively that also displayed altered gene expression in CRC tumors.ConclusionsOur mechanistic data support the notion that fructose has a greater CRC-related effect in right than left AA colon, alluding to a potential role for fructose in contributing to racial disparities in CRC.
An Early Adverse Drug Event Detection Approach with False Discovery Rate Control
Authors: Shi Yi , Peng Xueqiao , Liu Ruoqi , Sun Anna , Yang Yuedi , Zhang Ping , Zhang Pengyue 
Published: June 2023

AbstractAdverse drug event (ADE) is a significant challenge in clinical practice. Many ADEs have not been identified timely after the approval of the corresponding drugs. Despite the use of drug similarity network demonstrates early success on improving ADE detection, false discovery rate (FDR) control remains unclear in its application. Additionally, performance of early ADE detection has not been explicitly investigated under the time-to-event framework. In this manuscript, we propose to use the drug similarity based posterior probability of null hypothesis for early ADE detection. The proposed approach is also able to control FDR for monitoring a large number of ADEs of multiple drugs. The proposed approach outperforms existing approaches on mining labeled ADEs in the US FDA’s Adverse Event Reporting System (FAERS) data, especially in the first few years after the drug initial reporting time. Additionally, the proposed approach is able to identify more labeled ADEs and has significantly lower time to ADE detection. In simulation study, the proposed approach demonstrates proper FDR control, as well as has better true positive rate and an excellent true negative rate. In our exemplified FAERS analysis, the proposed approach detects new ADE signals and identifies ADE signals in a timelier fashion than existing approach. In conclusion, the proposed approach is able to both reduce the time and improve the FDR control for ADE detection.
Population-level effectiveness of pre-exposure prophylaxis for HIV prevention among men who have sex with men in Montréal: a modelling study of surveillance and survey data
Authors: Doyle Carla M , Milwid Rachael M , Cox Joseph , Xia Yiqing , Lambert Gilles , Tremblay Cécile , Otis Joanne , Boily Marie-Claude , Baril Jean-Guy , Thomas Réjean , Blais Alexandre Dumont , Trottier Benoit , Grace Daniel , Moore David M. , Mishra Sharmistha , Maheu-Giroux Mathieu 
Published: June 2023

AbstractBackgroundHIV pre-exposure prophylaxis (PrEP) has been recommended and partly subsidized in Québec since 2013. We aimed to evaluate the population-level impact of PrEP on HIV transmission among men who have sex with men (MSM) in Montréal over 2013-2021.MethodsWe used an agent-based mathematical model of sexual HIV transmission to estimate the fraction of HIV acquisitions averted by PrEP compared to a counterfactual scenario without PrEP. The model was calibrated to local MSM survey and cohort data and accounted for COVID-19 pandemic impacts on sexual activity, prevention, and care. To assess potential optimization strategies, we modelled hypothetical scenarios prioritizing PrEP to MSM with high sexual activity or aged ≤45 years, increasing coverage to levels achieved in Vancouver (where PrEP is free-of-charge), and improving retention.ResultsOver 2013-2021, the estimated annual HIV incidence decreased from 0.4 (90% credible interval [CrI]: 0.3-0.6) to 0.2 (90%CrI: 0.1-0.2) per 100 person-years. PrEP coverage in HIV-negative MSM remained low until 2015 (<1%). Afterward, coverage increased to a maximum of 10% (15% of those eligible for PrEP) and the cumulative fraction of HIV acquisitions averted over 2015-2021 was 20% (90%CrI: 11%-30%). The hypothetical scenarios modelled showed that PrEP could have averted up to 63% (90%CrI: 54%-70%) of acquisitions if coverage reached 10% in 2015 and 30% in 2019, like in Vancouver.InterpretationPrEP reduced population-level HIV transmission among Montréal MSM. However, our study suggests missed prevention opportunities and provides support for public policies that provide PrEP free-of-cost to MSM at high risk of HIV acquisition.
Cytosponge procedures produce fewer respiratory aerosols and droplets than oesophagogastro-duodenoscopies
Authors: Gordon George S.D. , Warburton Samantha , Parkes Sian , Kerridge Abigail , Parra-Blanco Adolfo , Ortiz-Fernandez-Sordo Jacobo , Fitzgerald Rebecca C. 
Published: June 2023

AbstractBackground and AimsOesophagogastro duodenoscopies (OGD) are aerosol generating procedures (AGP) that may spread respiratory pathogens. We aim to investigate production of airborne aerosols and droplets during Cytosponge procedures, which are being evaluated in large-scale research studies and NHS implementation pilots to reduce endoscopy backlogs.Design and MethodsWe measured 18 Cytosponge and 37 OGD procedures using a particle counter (diameters 0.3μm-25μm) taking measurements 10cm from the mouth. Two particle count analyses were performed: whole procedure and event-based.ResultsDirect comparison with duration-standardised OGD procedures shows Cytosponge procedures produce 2.16x reduction (p<0.001) for aerosols and no significant change for droplets (p=0.332). Event-based analysis shows particle production is driven by throat spray (aerosols:138.1x reference, droplets:16.2x), which is optional, and removal of Cytosponge (aerosols:14.6x, droplets:62.6x). Cytosponge coughing produces less aerosols than OGD (2.82x,p<0.05).ConclusionsCytosponge procedures produce significantly less aerosols and droplets than OGD procedures and thus reduce two potential transmission routes for respiratory viruses.
Enhancing Kidney Failure Analysis: Web Application Development for Longitudinal Trajectory Clustering
Authors: Gu Yuan , Gong Yishu , Wang Mingyue , Jiang Song , Li Chen , Yuan Zheng 
Published: June 2023

AbstractKidney failure is a critical health condition with significant impact on patient well-being and healthcare systems worldwide. Analyzing the longitudinal trajectory of kidney function is crucial for understanding disease progression, predicting outcomes, and personalizing treatment strategies. This paper proposes a novel approach utilizing latent longitudinal trajectory clustering techniques by incorporating survival information to analyze kidney failure and explore patterns within patient populations. Besides, we also developed a web application to provide visualize and intuitive way to explore the relationship between estimated glomerular filtration rate (EGFR) progression and survival outcomes, helping researchers and clinicians gain valuable insights. By identifying distinct subgroups, this analysis can aid in early detection, risk stratification, and treatment optimization. The proposed methodology holds promise for improving patient care and outcomes in the field of nephrology.
Pangenome graphs improve the analysis of rare genetic diseases
Authors: Groza Cristian , Schwendinger-Schreck Carl , Cheung Warren A. , Farrow Emily G. , Thiffault Isabelle , Lake Juniper , Rizzo William B. , Evrony Gilad , Curran Tom , Bourque Guillaume , Pastinen Tomi 
Published: June 2023

AbstractRare DNA alterations that cause heritable diseases are only partially resolvable by clinical next-generation sequencing due to the difficulty of detecting structural variation (SV) in all genomic contexts. Long-read, high fidelity genome sequencing (HiFi-GS) detects SVs against reference genomes with increased sensitivity and also enables the assembly of personal and graph genomes. We leveraged standard reference genomes, publicly available human haploid assemblies (n=94), together with a large collection of HiFi-GS data from a rare disease program (Genomic Answers for Kids, GA4K, n=574 assemblies). These data allowed us to build a deep population graph genome distinguishing very rare SVs from recurrent polymorphisms. Using graphs to discover SVs, we obtained a higher level of reproducibility than that obtained by the standard reference approach. We observed over 200,000 SV alleles unique to the rare disease GA4K cohort, including nearly 1,000 rare variants that impact coding sequence. With improved specificity for rare SVs, we isolate 30 candidate SVs in phenotypically prioritized genes, including known disease SVs. We isolate novel diagnostic SV inKMT2Ein a patient demonstrating use of personal assemblies coupled with pangenome graphs as a new handle for rare disease genomics.
Prefrontal Cortex Astroglia Modulate Anhedonia-like Behavior
Authors: Codeluppi S.A. , Xu M. , Bansal Y. , Lepack A.E. , Duric V. , Chow M. , Muir J. , Bagot R.C. , Licznerski P. , Wilber S.L. , Sanacora G. , Sibille E. , Duman R.S. , Pittenger C. , Banasr M. 
Published: June 2023

AbstractReductions of astroglia expressing glial fibrillary acidic protein (GFAP) are consistently found in the prefrontal cortex (PFC) of patients with depression and in rodent chronic stress models. Here, we examine the consequences of PFC GFAP+ cell depletion and cell activity enhancement on depressive-like behaviors in rodents. Using viral expression of diphtheria toxin receptor in PFC GFAP+ cells, which allows experimental depletion of these cells following diphtheria toxin administration, we demonstrated that PFC GFAP+ cell depletion induced anhedonia-like behavior within 2 days and lasting up to 8 days, but no anxiety-like deficits. Conversely, activating PFC GFAP+ cell activity for 3 weeks using designer receptor exclusively activated by designer drugs (DREADDs) reversed chronic restraint stress-induced anhedonia-like deficits, but not anxiety-like deficits. Our results highlight a critical role of cortical astroglia in the development of anhedonia and further support the idea of targeting astroglia for the treatment of depression.