bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coupling of metabolomics and exome sequencing reveals graded effects of rare damaging heterozygous variants on gene function and resulting traits and diseases
Authors: Scherer Nora , Fässler Daniel , Borisov Oleg , Cheng Yurong , Schlosser Pascal , Wuttke Matthias , Patil Suraj , Meiselbach Heike , Telkämper Fabian , Berger Urs , Grünert Sarah , Sekula Peggy , Schultheiss Ulla T. , Li Yong , Köttgen Michael , Oefner Peter J. , Knauf Felix , Eckardt Kai-Uwe , Thiele Ines , Schmidts Miriam , Hertel Johannes , Köttgen Anna 
Published: October 2023

AbstractGenetic studies of the metabolome can uncover enzymatic and transport processes shaping human metabolism. Using WES-based rare variant aggregation testing to detect genes associated with levels of 1,294 plasma and 1,396 urine metabolites, we discovered 235 gene-metabolite associations, many previously unreported. Validation through genetic and new computational approaches (in silicogene knockouts in whole-body models of human metabolism) provided orthogonal evidence that population-based studies of rare, damaging variants in the heterozygous state permit inferences usually obtained from inborn errors of metabolism. Allelic series of functional variants in transporters responsible for transcellular sulfate reabsorption (SLC13A1, SLC26A1) exhibited graded effects on plasma sulfate and human height, and pinpointed alleles that strongly increased risk for dozens of musculoskeletal traits and diseases in the population. We present a powerful approach to identify new players in incompletely characterized human metabolic reactions, and to reveal metabolic readouts of disease risk to inform disease prevention and treatment.
Computational discovery of co-expressed antigens as dual targeting candidates for cancer therapy through bulk, single-cell, and spatial transcriptomics
Authors: Chekalin Evgenii , Paithankar Shreya , Shankar Rama , Xing Jing , Xu Wenfeng , Chen Bin 
Published: October 2023

AbstractMotivationBispecific antibodies (bsAbs) that bind to two distinct surface antigens on cancer cells are emerging as an appealing therapeutic strategy in cancer immunotherapy. However, considering the vast number of surface proteins, experimental identification of potential antigen pairs that are selectively expressed in cancer cells and not in normal cells is both costly and time-consuming. Recent studies have utilized large bulk RNA-seq databases to propose bispecific targets for various cancers. But, co-expressed pairs derived from bulk RNA-seq do not necessarily indicate true co-expression of both markers in the same cell. Single-cell RNA-seq (scRNA-seq) can circumvent this issue but the issues in dropouts and low-coverage of transcripts impede the large-scale characterization of co-expressed pairs.ResultsWe present a computational pipeline for bsAbs identification which combines the advantages of bulk and scRNA-seq while minimizing the issues associated with using these approaches separately. We select Hepatocellular Carcinoma (HCC) as a case study to demonstrate the utility of the approach. First, using the bulk RNA-seq samples in the OCTAD database, we identified target pairs that most distinctly differentiate tumors cases from healthy controls. Next, we confirmed our findings on the scRNA-seq database comprising 39,361 healthy cells from vital organs and 18,000 malignant cells from HCC. The top pair was GPC3∼MUC13, where both genes are co-expressed on the surface of over 30% of malignant HCCs and have very low expression in other cells. Finally, we leveraged the emerging spatial transcriptomic to validate the co-expressed pairin situ.Availability and ImplementationA standalone R package for bsAbs identification in bulk data is available via GitHub (https://github.com/Lionir/bsAbsFinder).
What is the relationship between raising the minimum legal sales age of tobacco above 20 and cigarette smoking? A systematic review
Authors: Davies Nathan , Bogdanovica Ilze , McGill Shaun , Murray Rachael L 
Published: October 2023

ABSTRACTObjectivesTo determine whether raising the minimum legal sales age of tobacco (MLSA) to 20 or above is associated with reduced prevalence of smoking compared to an MLSA set at 18 or below through systematic review.Data sourcesFollowing a pre-registered protocol on PROSPERO (ref: CRD42022347604), six databases of peer-reviewed journals were searched from January 2015 to September 2023. Backwards and forwards reference searching was conducted.Study selectionStudies that assessed the association between MLSAs of 20 and above with cigarette smoking or cigarette sales for children and young people aged 11-20. Assessments on e-cigarettes were excluded.Data extractionPairs of reviewers independently extracted study data and used ROBINS-I to assess risk of bias.Data synthesisNarrative methods were used to synthesise findings. 19 studies were reviewed, from which 26 effect estimates were extracted. All studies evaluated Tobacco 21 laws in the United States. Just under half of estimates found a statistically significant association with reduced current cigarette smoking or sales, just over half found no statistically significant association, and one estimate found an association with increased cigarette smoking. The positive association appeared to be stronger for older age groups, those from a Hispanic/Latinx background and those with lower education. The degree of study bias was variable.ConclusionsThere is evidence that raising the MLSA for tobacco to 21 reduces cigarette sales and current cigarette smoking amongst those aged 11-20 and has potential to reduce health inequalities. Further research beyond the United States would support generalisability to other settings.
The comparison of handpiece anti-surge system and main body in cataract surgery
Authors: Kim Hyo Won , Kim Inkee , Kim Hyun Seung , Kim Eun Chul 
Published: October 2023

AbstractBackground/aimsTo compare the efficacy of the Centrion handpiece anti-surge system (Active Sentry®) and main body according to the grade of nucleosclerosis.Methods600 eyes of 415 patients who underwent cataract surgery was retrospectively enrolled. Intraoperative parameters included phacoemulsification time (seconds), cumulative dissipated energy (CDE), and balanced salt solution (BSS) use (ml). Clinical measurements were made preoperatively and at one day, one month, two, and three months postoperatively, including the best corrected visual acuity (BCVA), and the corneal endothelial cell (CEC) count in the handpiece group (N=300) and main body group (N=300). Within the anti-surge group, the number of anti-surge system activated was collected.ResultsAnti-surge (times), phacoemulsification time, CDE, and BSS use significantly increased with increasing nucleosclerosis grades and in zonule weakness, poor mydriasis, and pseudoexfoliation syndrome in handpiece group, respectively (p < 0.05). Phacoemulsification time, CDE, and BSS use of handpiece group were significantly lower than those of main body group (p < 0.05). Phacoemulsification time, CDE, and CEC loss of handpiece group were significantly lower than those of main body group in nucleosclerosis grade 5 and 6 (p < 0.05). BSS uses of handpiece group were significantly lower than those of main body group in all nucleosclerosis grade (p < 0.05).ConclusionBecause of the fast-reacting anti-surge, Intraoperative parameters were saved in handpiece anti-surge system rather than in main body. Therefore, the anti-surge system in the Centrion handpiece helps the surgeon perform safer cataract surgery in higher nucleosclerosis grade, zonule weakness, poor mydriasis, and pseudoexfoliation syndrome.SynopsisAnti-surge system in the Centrion handpiece helps the surgeon perform safer cataract surgery in higher nucleosclerosis grade, zonule weakness, poor mydriasis, and pseudoexfoliation syndrome.WHAT IS ALREADY KNOWN ON THIS TOPICActive Sentry handpiece was reported to be as safe and efficacious as the Ozil handpiece, with the benefit of operating at lower intraocular pressure levelsWHAT THIS STUDY ADDSAnti-surge system in the Centrion handpiece helps the surgeon perform safer cataract surgery in higher nucleosclerosis grade, zonule weakness, poor mydriasis, and pseudoexfoliation syndrome.HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYWith anti-surge system in the Centrion handpiece, phacoemulsification can be performed effectively and safely in patients with complicated cataract.
Perioperative Enteral Fasting Duration Scores In Double Digits: A Seven-Year Long Cross-Sectional Retrospect By A Single Institution Among Its Patients Undergoing Extracapsular Cataract Extraction With Intraocular Lens Implantation
Authors: Gupta Deepak 
Published: October 2023

AbstractBackgroundPerioperative fasting period can be very variable which must be quantified at institutional level so that the institutions can re-formulate their local policies while adapting to updated national and international guidelines.ObjectiveThe purpose of this retrospective study was to ascertain the total duration of perioperative fasting among patients who underwent extracapsular cataract extraction with intraocular lens implantation at the institution during 2016-2022 (a seven-year period).MethodsA query was run by information technology team in the institutional electronic medical records to extract lists of de-identified patients who underwent extracapsular cataract extraction with intraocular lens implantation at the institution during 2016-2022 wherein total perioperative fasting time was calculated from Last Food Intake to In Phase I Time (for solids) and Last Fluid Intake to In Phase I Time (for liquids).ResultsData of 6722 patients was analyzed wherein patients had 4-48 hours of nothing by mouth in terms of fluid perioperatively and 10-48 hours nothing by mouth in terms of food perioperatively. Perioperative fasting durations were in double digits across all age and sex based groups whether it was the mean duration with its confidence limits or median duration with its lower and upper quartiles.ConclusionRather than remaining in single digits, perioperative enteral fasting durations were very commonly in double digits at the institution among its patients undergoing extracapsular cataract extraction with intraocular lens implantation.
Cohort profile: working age adults accessing secondary mental health services in South London (UK) and benefits – a data linkage of electronic mental health records and benefits data
Authors: Phillips Ava , Leal Ray , Jewell Amelia , Madan Ira , Downs Johnny , Broadbent Matthew , Hotopf Matthew , Dorrington Sarah , Fear Nicola T. , Stevelink Sharon A.M. 
Published: October 2023

AbstractThis study describes a cohort of working age adults from a novel data linkage. The data linkage is comprised of routine electronic mental health records from The South London and Maudsley (SLaM) NHS Foundation Trust and benefits records from The Department for Work and Pensions (DWP). The data linkage spans 15 years, with SLaM data covering the period 2007-2019 and DWP data covering the period 2005-2020. The linkage was established to investigate the interrelationships between benefit receipt and mental health (including mental health service utilisation) in patients accessing secondary mental health services in South London, UK. Clinical data from SLaM includes information on sociodemographics, diagnoses, assessments, treatments, interventions, and service interaction. Benefits data from DWP provides information on benefit types received, spell dates and entitlement amounts, work capability assessments and work programme access.This cohort included all working age adults (aged 18-65 years) referred to/receiving treatment from SLaM services between January 2007 and June 2019. We report the sociodemographics and psychiatric diagnoses of n=150,348 working age adults, as well as the types of benefits received. We showed that 78.3% of working age adults received a benefit relating to unemployment or work-related income, sickness or disability, or a housing benefit, and that 68.0% of this group had a recorded primary psychiatric diagnosis. The most commonly received diagnoses were alcohol related disorders and substance related disorders (17.2%), followed by mood (affective) disorders (16.5%). We also observed that nearly 70% of claimants who had received more than one benefit were residing in the two most deprived areas across the South London boroughs covered by SLaM.
Patient’s Satisfaction with Eye Care Services from tertiary Eye hospital in Nepal
Authors: Shah Ranjan , Mishra Sailesh Kumar , Sharma Prakriti 
Published: October 2023

AbstractPurposeThis study was conducted to assess the level of patient satisfaction with the eye care services received from different tertiary eye hospitals, running under Nepal Nepal Netra Jyoti (NNJS) Sangh, of Madhesh Province, Nepal over a 3-month period (October-December) 2017.MethodsA Cross-sectional based study with client exit interviews were done, using pretested Likert scale tool in sample of 1190 (P=0.5, and 95% CI) consenting patients after receiving the ophthalmic care enrolled in the mentioned tertiary eye hospitals of Madhesh Province. Data on Behavior of the service provider, Services and facilities provided by the hospital was analyzed with the level of patient’s satisfaction. A Pearson’s chi-square test was used to examine the relationship between overall satisfaction and the dependent variables.ResultsOnly 3.8 % of patients reported visiting the hospital more than four times. The main reasons for choosing their respective hospital was the ‘quality of services’ delivered through modern equipment at affordable costs (53 %) followed by easy access to hospital (39%). The average waiting time was 58 min, with a range of 5-240 min. Level of education (P<0.05), Socioeconomic status (P<0.05), Waiting time (P<0.05), Hospital operating hours (P<0.05), Cleanliness (P<0.05) and Cost of Service (P<0.05) were significantly associated with the overall satisfaction with the services. Behavior of the service providers did not play a statistically significant role in overall satisfaction.ConclusionPatient satisfaction is a highly desirable outcome of clinical care and may even be an element of health status itself. Our data showed that a significant proportion (95%) of patients were satisfied, or highly satisfied overall (across all parametric measures), and that personal experience, beliefs and background may play a confounding factor in satisfaction. As a result, it can be safely concluded that perceived quality and performance in the hospitals are exceptional.
Ghost interactions: revealing missing protein-ligand interactions using AlphaFold predictions
Authors: Escobedo Nahuel , Saldaño Tadeo , Donagh Juan Mac , Sawicki Luciana Rodriguez , Palopoli Nicolas , Alberti Sebastian Fernandez , Fornasari Maria Silvina , Parisi Gustavo 
Published: October 2023

AbstractProtein–ligand interactions represent an essential step in understanding molecular recognition, an intense field of research for many scientific areas. Structural biology has played a central role in unveiling protein-ligand interactions, but current techniques are still not able to reliably describe the interactions of ligands with highly flexible regions. In this work we explored the capacity of AlphaFold2 (AF2) to estimate the presence of interactions between ligands and residues belonging to disordered regions, which we called “ghost interactions” as they are missing in the crystallographic derived structures. We found that AF2 models are good predictors of regions associated with order-disorder transitions. Additionally, we found that AF2 predicts residues making ghost interactions with ligands, which are mostly buried and show a differential evolutionary conservation. Our findings could fuel current areas of research that consider intrinsically disordered proteins as potentially valuable targets for drug development, given their biological relevance and associated diseases.
Physical activity in adult users of inpatient mental health services: a scoping review
Authors: Tew Garry A. , Peckham Emily , Ker Suzy , Smith Jo , Hodgson Philip , Machaczek Katarzyna K. , Faires Matthew 
Published: October 2023

AbstractPeople with severe mental illness engage in considerably less physical activity than those without. They also experience premature mortality of around 10–25 years. A large proportion of these premature deaths are attributed to modifiable behaviours, including physical activity. The inpatient environment provides an opportunity to support people to become more physically active; however, there is limited evidence on which interventions are most successful and what contextual factors affect their delivery. A scoping review was conducted to help understand the extent and type of evidence in this area and identify research gaps. We included studies of physical activity in adult inpatient mental health services published in peer-reviewed journals. Reviews, meta-analyses, and papers focusing on eating disorder populations were excluded. We searched the MEDLINE, CINAHL, PsycINFO, ASSIA and Web of Science databases for relevant studies published in English. We extracted data on study design, participant characteristics, intervention and control conditions, key findings, and research recommendations. We used a descriptive analytical approach and results are presented in tables and figures. Of 27,286 unique records screened, 210 reports from 182 studies were included. Sixty-one studies reported on correlates of physical activity, and 139 studies reported on physical activity interventions. Most intervention studies used a single-group, pre-post design (40%) and included fewer than 100 participants (86%). Ninety percent of interventions delivered physical activity directly to participants, and 50% included group-based sessions. The duration, type, frequency and intensity of sessions varied. Mental health was the most commonly reported outcome (64%), whereas physical activity was rarely an outcome (13%). Overall, there is a modest but growing body of research on physical activity in adult users of inpatient mental health services. More high-quality trials are needed to advance the field, and future research should target neglected intervention types, outcomes, populations and settings.
Derivation and validation of a non-invasive optoacoustic imaging biomarker for patients with intermittent claudication
Authors: Caranovic Milenko , Kempf Julius , Li Yi , Regensburger Adrian P. , Günther Josefine S. , Träger Anna P. , Lang Werner , Meyer Alexander , Wagner Alexandra L. , Woelfle Joachim , Raming Roman , Paulus Lars-Philip , Buehler Adrian , Uter Wolfgang , Uder Michael , Behrendt Christian-Alexander , Neurath Markus F. , Waldner Maximilian J. , Knieling Ferdinand , Rother Ulrich 
Published: October 2023

AbstractBackgroundMultispectral optoacoustic tomography (MSOT), a molecular sensitive ultrasound, offers a non-invasive diagnostic approach to image the deep-tissue biomarkers.ObjectivesThe authors aimed to investigate the diagnostic accuracy of MSOT to distinguish between healthy volunteers (HV) and patients with intermittent claudication (IC) by assessing hemoglobin-related biomarkers in calf muscle tissue.MethodsIn this monocentric, cross-sectional diagnostic trial using derivation (DC) and validation cohorts (VC) yll subjects underwent standardized PAD diagnostics. This included pulse palpation, ankle brachial index (ABI), duplex sonography, 6-minute walk test (6MWT), and assessment of health-related quality of life (VASCUQOL-6). The vascular occlusion profile in IC patients was confirmed by angiography (aggregated TransAtlantic Inter-Society Consensus classification, aTASC). MSOT imaging of calf muscle was performed before and after standardized heel raise provocation.ParticipantsOf 123 screened individuals, 102 completed the study. MSOT-derived oxygenation (msO2) after the exercise differentiated IC and HV with an area under curve the receiver operator characteristics curve (AUROC) in DC by 0.99 (95%CI 0.97;1.00, p<0.001, sensitivity: 100%, specificity: 95.8%) and in the VC by 0.95 (95%CI 0.95;1.00, p<0.001, sensitivity: 96.2%, specificity: 96.0%). mSO2positively correlated with the ABI post-exercise (R=0.83, 95%CI 0.75;0.88, P<0.001), the absolute walking distance in the 6MWT (R=0.77, 95%CI 0.68;0.84, P<0.001), the VASCUQOL-6 (R=0.79, 95%CI 0.70;0.85, P<0.001) and negatively with aTASC classification (R=-0.80, 95%CI -0.86;-0.72, P<0.001).ConclusionsPost-exercise MSOT-derived saturation in the calf muscle was validated as a new and promising diagnostic biomarker to distinguish between HV and IC patients yielding high sensitivity and specificity. (NCT05373927)
Health journal coverage of climate change and health: a bibliometric study
Authors: Muhia Joy , Rethlefsen Melissa L. , Rossington Ben , Wedmore Florence , Pattnaik Anandita , Smith Richard , Schroter Sara 
Published: October 2023

ABSTRACTObjectivesTo find what proportion of a broad set of health journals have published on climate change and health, how many articles they have published, and when they first published on the subject.DesignBibliometric study.Setting and particbipantsWe conducted electronic searches in Ovid MEDLINE ALL for articles about climate change and human health published from 1860 to 31 December 2022 in 330 health journals. There were no limits by language or publication type. Results were independently screened by two raters for article eligibility.ResultsAfter screening there were 2932 eligible articles published across 253 of the 330 journals between 1947 and 2022; most (2795/2932; 95%) were published in English. A few journals published articles in the early 90s, but there has been a rapid increase since about 2006. We were unable to categorise the types of publication but estimate that fewer than half are research papers. While articles were published in journals in 39 countries, two-thirds (1929/2932; 66%) were published in a journal published in the UK or the US. Almost a quarter (77/330; 23%) of the journals published no eligible articles, and almost three-quarters (241/330; 73%) published five articles or fewer. The publication of joint editorials in over 200 journals in 2021 and 2022 boosted the number of journals publishing something on climate change and health. A third of the (112/330; 34%) journals in our sample published at least one of the joint editorials, and almost a third of those (32/112; 29%) were publishing on climate change and health for the first time.ConclusionsHealth journals are rapidly increasing the amount they publish on climate change and health, but despite climate change being the major threat to global health many journals had until recently published little or nothing. A joint editorial published in multiple journals increased coverage, and for many journals it was the first thing they published on climate change and health.Strengths and limitations of this studyWe looked at coverage of climate change at both the article and journal level from 1860 to 2022; previous bibliometric studies have analysed results only at the article level and in restricted time periodsTwo independent raters screened the title and abstract (where available) of every article identified by the MEDLINE search to assess eligibilityJournals not currently indexed in MEDLINE had to be excluded as hand searching was not feasible for such a large sample of journalsIt’s important to be cautious in generalising to all health journals from our sampleOur study included analysis of an intervention (publication of the joint editorials in multiple journals) to increase coverage on climate change and health in health journals.