bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association study and genomic risk prediction of age-related macular degeneration in Israel
Authors: Grunin Michelle , Triffon Daria , Beykin Gala , Rahmani Elior , Schweiger Regev , Tiosano Liran , Khateb Samer , Hagbi-Levi Shira , Rinsky Batya , Munitz Refael , Winkler Thomas W , Heid Iris M , Halperin Eran , Carmi Shai , Chowers Itay 
Published: September 2023

AbstractPurposeThe risk of developing age-related macular degeneration(AMD) is influenced by genetic background. In 2016, International AMD Genomics Consortium(IAMDGC) identified 52 risk variants in 34 loci, and a polygenic risk score(PRS) based on these variants was associated with AMD. The Israeli population has a unique genetic composition: Ashkenazi Jewish(AJ), Jewish non-Ashkenazi, and Arab sub-populations. We aimed to perform a genome-wide association study(GWAS) for AMD in Israel, and to evaluate PRSs for AMD.MethodsFor our discovery set, we recruited 403 AMD patients and 256 controls at Hadassah Medical Center. We genotyped all individuals via custom exome chip. We imputed non-typed variants using cosmopolitan and AJ reference panels. We recruited additional 155 cases and 69 controls for validation. To evaluate predictive power of PRSs for AMD, we used IAMDGC summary statistics excluding our study and developed PRSs via either clumping/thresholding or LDpred2.ResultsIn our discovery set, 31/34 loci previously reported by the IAMDGC were AMD associated with P<0.05. Of those, all effects were directionally consistent with the IAMDGC and 11 loci had a p-value under Bonferroni-corrected threshold(0.05/34=0.0015). At a threshold of 5x10-5, we discovered four suggestive associations inFAM189A1,IGDCC4,C7orf50, andCNTNAP4. However, only theFAM189A1variant was AMD associated in the replication cohort after Bonferroni-correction. A prediction model including LDpred2-based PRS and other covariates had an AUC of 0.82(95%CI:0.79-0.85) and performed better than a covariates-only model(P=5.1x10-9).ConclusionsPreviously reported AMD-associated loci were nominally associated with AMD in Israel. A PRS developed based on a large international study is predictive in Israeli populations.
Exploring the diversity of participants with dementia taking part in research: a mixed methods study
Authors: Bajwa Rupinder Kaur , Howe Louise , Agbonmwandolor Joy O. , Cowley Alison , Adams Emma J. , Goldberg Sarah , Harwood Rowan H. 
Published: September 2023

AbstractIntroductionDementia is becoming increasingly prevalent in the UK. Older adults from black and south Asian communities have a higher risk for dementia due to an increased prevalence of dementia specific risk factors such as hypertension, diabetes, and heart disease. Deprivation has also been linked to an increased risk of dementia. Ethnic minority and lower socioeconomic groups are underrepresented in dementia research. The aim of this study was to explore factors influencing diversity in dementia and rehabilitation research within the context of the Promoting Activity, Independence, and Stability in Early Dementia (PrAISED) randomised controlled trial (RCT).MethodsWe conducted an exploratory sequential mixed methods study to explore disparities in socioeconomic and ethnic diversity between the PrAISED RCT population and recruitment pathways used in one study site (Nottinghamshire) and compared these with regional and national data. We aimed to collate and summarise data available on ethnicity and deprivation for recruitment/referral pathways (Nottinghamshire site) and the PrAISED cohort (all sites). Additionally, we interviewed healthcare professionals (n=2), researchers (n=2) and members of black and south Asian communities (n=4) to explore barriers to participating in research for people with dementia.ResultsUnder 2% of the overall PrAISED RCT sample (across all sites) were from a non-white ethnic minority background and a third of participants lived in areas with the least deprivation. Referrals to memory assessment services in Nottinghamshire included people from diverse socioeconomic backgrounds, with 7.3% being from non-white ethnic minority communities. Through interviews, several barriers to healthcare, research and rehabilitation were identified. Healthcare barriers included lack of awareness of dementia, mistrust, stigma, fear, and lack of culturally appropriate services. Research barriers included recruitment routes, awareness of research, language, and recruiter beliefs. Barriers to rehabilitation research included a lack of use of culturally appropriate language, more culturally specific barriers, and lack of representation.ConclusionParticipants recruited to the PrAISED RCT were mainly white and socioeconomically privileged. Data recording and access around ethnicity is still inconsistent, making it difficult to ascertain at which point services and research become inaccessible for people from underserved communities. Future research needs to work with these communities to develop innovative solutions to overcome the barriers identified in this study and to put recommendations made into practice.
Designing a Library of Lived Experience for Mental Health: integrated realist synthesis and experience-based co-design study
Authors: Marshall Paul , Lobban Fiona , Barbrook John , Collins Grace , Foster Sheena , Glossop Zoe , Inkster Clare , Jebb Paul , Johnston Rose , Khan Hameed , Lodge Christopher , Machin Karen , Michalak Erin E. , Powell Sarah , Russell Samantha , Rycroft-Malone Jo , Slade Mike , Whittaker Lesley , Jones Steven 
Published: September 2023

ABSTRACTObjectiveLiving Library ‘Readers’ can learn about experiences of others through conversations with living ‘Books’. This study sought to generate a realist programme theory and a theory-informed implementation guide for a Library of Lived Experience for Mental Health (LoLEM).DesignIntegrated realist synthesis and experience-based co-design.SettingTen online workshops with participants based in the North of England.ParticipantsThirty-one participants with a combination of personal experience of using mental health services, caring for someone with mental health difficulties, and/or working in mental health support roles.ResultsDatabase searches identified 30 published and grey literature evidence sources which were integrated with data from 10 online co-design workshops. The analysis generated a programme theory comprising five context-mechanism-outcome (CMO) configurations. For Readers, direct conversations humanise others’ experiences (CMO 2) and provide the opportunity to flexibly explore new ways of living (CMO 3). Through participation in a Living Library, Books may experience personal empowerment (CMO 4), while the process of self-authoring and co-editing their story (CMO 5) can contribute to personal development. This programme theory informed the co-design of an implementation guide highlighting the importance of tailoring event design and participant support to the contexts in which LoLEM events are held.ConclusionsThe LoLEM has appeal across stakeholder groups and can be applied flexibly in a range of mental health-related settings. Implementation and evaluation are required to better understand the positive and negative impacts on Books and Readers.RegistrationPROSPERO CRD42022312789Strengths and limitations of this studyThis study used a novel, iterative, and creative approach to integrating theory development and intervention co-design.The programme theory provides a conceptual basis for further evaluation of a LoLEM, including outcomes for those participating in events as ‘Books’ and ‘Readers’.This study informed detailed, co-designed implementation guidance for use by LoLEM organisers.However, the LoLEM is yet to be delivered as a sustained programme of events, so long-term impacts require further investigation.
Fast clinical trial identification using fuzzy-search elastic searches: retrospective validation with high-quality Cochrane benchmark
Authors: Otte Willem M , van IJzendoorn David G P , Habets Philippe C , Vinkers Christiaan H 
Published: September 2023

AbstractThe synthesis of treatment effects relies on systematic reviews of intervention trials. This process is often laborious due to the need for precise search queries and manual study identification. Recent advancements in database architecture and natural language processing (NLP) offer a potential solution by enabling faster, more flexible searches and automated extraction of information from unstructured texts.Our study assesses the effectiveness of NLP-based literature searches within a novel database structure in comparison to the Cochrane Database of Systematic Reviews. We created a user-friendly elastic search database containing 36 million PubMed-indexed entries. We developed reliable filters for identifying randomized clinical trials and clinical intervention studies, as well as extracting relevant subtext related to population and intervention.Our results indicate a high precision of 0.74, recall of 0.81, and F1-score of 0.77 for population subtext, and a precision of 0.70, recall of 0.71, and an F1-score of 0.70 for intervention subtext. Our approach efficiently identified included studies in 90% of systematic reviews, missing no more than two trials compared to Cochrane. Furthermore, it produced fewer total hits than a comparable PubMed keyword search, demonstrating the potential of the new database structure to enhance the efficiency and effectiveness of aggregating clinical evidence.
Quantity of SARS-CoV-2 RNA copies exhaled per minute during natural breathing over the course of COVID-19 infection
Authors: Lane Gregory , Zhou Guangyu , Hultquist Judd F. , Simons Lacy M. , Redondo Ramon Lorenzo- , Ozer Egon A. , McCarthy Danielle M. , Ison Michael G. , Achenbach Chad J. , Wang Xinkun , Wai Ching Man , Wyatt Eugene , Aalsburg Alan , Yang Qiaohan , Noto Torben , Alisoltani Arghavan , Ysselstein Daniel , Awatramani Rajeshwar , Murphy Robert , Theron Grant , Zelano Christina 
Published: September 2023

ABSTRACTSARS-CoV-2 is spread through exhaled breath of infected individuals. A fundamental question in understanding transmission of SARS-CoV-2 is how much virus an individual is exhaling into the environment while they breathe, over the course of their infection. Research on viral load dynamics during COVID-19 infection has focused on internal swab specimens, which provide a measure of viral loads inside the respiratory tract, but not on breath. Therefore, the dynamics of viral shedding on exhaled breath over the course of infection are poorly understood. Here, we collected exhaled breath specimens from COVID-19 patients and used RTq-PCR to show that numbers of exhaled SARS-CoV-2 RNA copies during COVID-19 infection do not decrease significantly until day 8 from symptom-onset. COVID-19-positive participants exhaled an average of 80 SARS-CoV-2 viral RNA copies per minute during the first 8 days of infection, with significant variability both between and within individuals, including spikes over 800 copies a minute in some patients. After day 8, there was a steep drop to levels nearing the limit of detection, persisting for up to 20 days. We further found that levels of exhaled viral RNA increased with self-rated symptom-severity, though individual variation was high. Levels of exhaled viral RNA did not differ across age, sex, time of day, vaccination status or viral variant. Our data provide a fine-grained, direct measure of the number of SARS-CoV-2 viral copies exhaled per minute during natural breathing—including 312 breath specimens collected multiple times daily over the course of infection—in order to fill an important gap in our understanding of the time course of exhaled viral loads in COVID-19.
Standardisation of cell-free DNA measurements: An International Study on Comparability of Low Concentration DNA Measurements using cancer variants
Authors: Burke Daniel , Devonshire Alison S. , Pinheiro Leonardo B. , Jones Gerwyn M. , Griffiths Kate R. , Fernandez Gonzalez Ana , Forbes-Smith Michael , McLaughlin Jacob , Emslie Kerry R. , Weidner Christopher , Mankertz Joachim , Leguizamon John E. , Medeiros Marcelo Neves de , Flatschart Roberto Becht , Saraiva Antonio M. , Beltrao Paulo Jose Iwakami , Divieto Carla , Revel Laura , Bae Young-Kyung , Dong Lianhua , Niu Chunyan , Wang Xia , Temisak Sasithon , Shibayama Sachie , Yalcinkaya Burhanettin , Akgoz Muslum , Macdonald Rainer , Plauth Annabell , Huggett Jim 
Published: September 2023

ABSTRACTFor the impact of genomic testing from liquid biopsies to be maximized, mechanisms to ensure reproducible and comparable test performance will be required. This can be established and maintained through reference measurement procedures and materials with property values that are internationally comparable through traceability to a common standard. To achieve this objective, an interlaboratory study was organised to explore digital PCR (dPCR) for standardisation of cell-free DNA (cfDNA) quantification.Blinded samples of wild-type/variant mixtures of two DNA sequences (BRAFp.V600E single nucleotide variant orEGFRexon 19 deletion) were provided to 12 laboratories. Laboratories independently designed and applied dPCR assays to determine absolute and relative quantities, with no guidance provided to harmonise the approach.The mean and coefficient of variation (CV) of copy number concentrations for variant sequences were 18 copies/μL (CV 7.2%) (BRAFvariant sample) and 9 copies/μL (CV 25%) (EGFRvariant sample) while the mean variant allele frequencies (vAF) were 8.0% (CV 5.3%) and 0.080% (CV 29%) respectively.This study demonstrated that dPCR was capable of exceptional technical accuracy for variant copy number concentration and vAF, even when different assays and platforms were used. This implies that dPCR offers a unique analytical methodology that can be deployed globally in supporting comparability for cfDNA testing based on the existing framework of the International System of units of measurement.
MAFB drives differentiation by permitting WT1 binding to podocyte specific promoters
Authors: Massa Filippo M. , Jian-Motamedi Fariba , Šerys Marijus , Tison Amelie , Loubat Agnès , Lacas-Gervais Sandra , Martin Luc , Belahbib Hassiba , Sarrazin Sandrine , Sieweke Michael H. , Schedl Andreas 
Published: September 2023

AbstractPodocytes are highly specialized cells, but their chromatin status and the precise molecular events leading to their differentiation remain poorly defined. Here we used ChIP-Seq analysis for H3K4me3, H3K4me1 and H3K27me3 to establish the histone methylation map in adult mouse podocytes. Our data demonstrate open chromatin across podocyte specific genes and reveals that genes expressed in the mesoderm lineage become actively repressed upon podocyte differentiation. To better understand the transcriptional control of podocyte differentiation, we studied the role of transcription factor MAFB. ChIP-Seq experiments and functional analysis in conditional knockout mice identified a set of direct MAFB targets includingNphs1,Nphs2, VegfaandTcf21. Loss ofMafBled to the deposition of extracellular matrix, progressive foot process effacement, and kidney disease. ChIP experiments in knockout animals revealed that during development MAFB is essential for H3K4me3 methylation and the recruitment of WT1 to the promoters of the podocyte specific genesNphs1andNphs2. Taken together our data reveal the crucial function of MAFB by permitting chromatin accessibility at podocyte-specific genes during development and maintaining terminal differentiation in adults.
PUFFFIN: A novel, ultra-bright, customisable, single-plasmid system for labelling cell neighbourhoods
Authors: Lebek Tamina , Malaguti Mattias , Elfick Alistair , Lowell Sally 
Published: September 2023

AbstractCell communication orchestrates development, homeostasis, and disease. Understanding these processes depends on effective methods to study how cells influence their neighbours. Here, we present Positive Ultra-bright Fluorescent Fusion For Identifying Neighbours (PUFFFIN), a novel cell neighbour-labelling system based upon secretion and uptake of a positively supercharged fluorescent protein s36GFP. To achieve sensitive labelling, we amplified the fluorescent signal by fusing s36GFP to the ultra-bright protein mNeonGreen. Secretor cells transfer s36GFP-mNeonGreen to neighbours while retaining a nuclear mCherry, making it straightforward to unambiguously identify, isolate, and profile neighbours of secretor cells. Transfer of the s36GFP-mNeonGreen fusion occurs within minutes, enabling even relatively transient interactions to be captured or tracked over time with live-imaging or flow cytometry. To enhance flexibility of use, we incorporated HaloTag technology to facilitate colour-of-choice labelling. To further increase the range of applications, we engineered a customisable single-plasmid construct composed of interchangeable components with option to incorporate any additional transgene. This allows users to manipulate the properties of a cell, while at the same time applying a fluorescent label to the surrounding cells. PUFFFIN offers a simple, sensitive, customisable approach to profile non-cell-autonomous responses to natural or induced changes in cell identity or behaviour in mammalian cells.Graphical abstract
Overnight fasting facilitates safety learning by changing the neurophysiological response to relief from threat omission
Authors: Papalini Silvia , Beckers Tom , Van Oudenhove Lukas , Vervliet Bram 
Published: September 2023

AbstractExcessive avoidance and slow extinction of fear are hallmarks of anxiety disorders. We have previously found that overnight fasting diminishes excessive avoidance and speeds up fear extinction by decreasing subjective relief during threat omissions. Since relief tracks the reward prediction error signal that governs safety learning, we hypothesized that these effects of fasting might be linked to a decreased activation in brain regions related to reward prediction error processing. Hence, we replicated our previous study in a 3T-MRI scanner. Overnight fasting increased effective avoidance and sped up fear extinction learning. During extinction, the fasting group showed lower activations in the ventromedial prefrontal cortex and nucleus accumbens in response to threat omissions signaled by a safe cue. Nucleus accumbens activations were modulated by relief in the control group. This study provides support for overnight fasting as an adjunct to treatments for anxiety, but the effects should be investigated in anxious patients.
Using methyl bromide for interspecies cell-cell signaling and as a reporter in a model soil consortium
Authors: Kim Jiwoo , Lu Li Chieh , Gao Xiaodong , Hofmockel Kirsten S. , Masiello Caroline A. , Silberg Jonathan J. 
Published: September 2023

AbstractSoil microbial communities with reduced complexity are emerging as model systems for studying consortia-scale phenotypes. To establish synthetic biology tools for studying these communities in hard-to-image environmental materials, we evaluated whether a single member of a model soil consortium (MSC) can be programmed to report on gene expression without requiring matrix disruption. For these studies, we targeted a five member MSC that includesDyadobacter fermentans,Ensifer adhaerens,Rhodococcussp003130705, Streptomycessp001905665, andVariovorax beijingensis. By coupling the expression of a methyl halide transferase to a constitutive promoter, we show thatVariovorax beijingensiscan be programmed to synthesize methyl halides that accumulate in the soil headspace at levels that are ≥24-fold higher than all other MSC members across a range of environmentally-relevant hydration conditions. We find that methyl halide production can report on a MSC promoter that is activated by changes in water potential, and we demonstrate that a synthetic gas signal can be read out directly using gas chromatography and indirectly using a soil-derivedMethylorubrumthat is programmed to produce a visual output in response to methyl halides. These tools will be useful for future studies that investigate how MSC respond to dynamic hydration conditions, such as drought and flood events induced by climate change, which can alter soil water potential and induce the release of stored carbon.
A study of genetic variants associated with skin traits in the Vietnamese population
Authors: Hoang Tham Hong , Vu Duc Minh , Vu Giang Minh , Nguyen Thien Khac , Do Nguyet Minh , Duong Vinh Chi , Pham Thang Luong , Tran Mai Hoang , Nguyen Ly Thi Khanh , Han Han Thi Tuong , Can Thuy Thu , Pham Thai Hong , Pham Tho Duc , Nguyen Thanh Hong , Do Huy Phuoc , Vo Nam S. , Nguyen Xuan-Hung 
Published: September 2023

AbstractBackgroundMost skin-related traits have been studied from Caucasian genetic background. A comprehensive study on skin-associated genetic effects on under-represented populations like Vietnam is needed to fill the gaps in the field.ObjectivesTo develop a computational pipeline to predict the effect of genetic factors on skin traits using public data (GWAS catalogs and whole genome sequencing (WGS) data of 1000 genomes project-1KGP) and in-house Vietnamese data (WGS and genotyping by SNP array). By using this information we may have a better understanding of the susceptibility of Vietnamese people.MethodsVietnamese cohorts of whole genome sequencing (WGS) of 1008 healthy individuals for the reference and 96 genotyping samples (which do not have any skin cutaneous issues) by Infinium Asian Screening Array-24 v1.0 BeadChip were employed to predict skin-associated genetic variants of 25 skin-related and micronutrients requirement traits in population analysis and correlation analysis. Simultaneously, we compared the landscape of cutaneous issues of Vietnamese people with other populations by assessing their genetic profiles.ResultsThe skin-related genetic profile of Vietnamese cohorts is similar at most with East Asian (JPT: Fst=0.036, CHB: Fst=0.031, CHS: Fst=0.027, CDX: Fst=0.025) in the population study. In addition, we identified pairs of skin traits being at high risk of frequent co-occurrence (such as skin aging and wrinkles (r = 0.45, p =1.50e-5) or collagen degradation and moisturizing (r = 0.35, p = 1.1e-3).ConclusionThis is the first investigation in Vietnam to explore genetic variants of facial skin. These findings could improve inadequate skin-related genetic diversity in the currently published database.