bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide epistasis analysis reveals significant epistatic signals associated with Parkinson’s disease risk
Authors: Cisterna-Garcia Alejandro , Bustos Bernabe I , Bandres-Ciga Sara , Leal Thiago P , Sarihan Elif I , Jok Christie , Krainc Dimitri , Mata Ignacio F , Lubbe Steven J , Botia Juan A 
Published: December 2024

Abstract
Genome-wide association studies (GWAS) have increased our understanding of Parkinson’s disease (PD) genetics by identifying common disease-associated variants. However, much of the heritability remains unaccounted for and we hypothesized that this could be partly explained by epistasis, the statistical interaction between two or more genetic variants.
Here, we developed a genome-wide non-exhaustive epistasis screening pipeline called Variant-variant interaction through variable thresholds (VARI3) and applied it to diverse PD GWAS cohorts.
We used 14 cohorts of European ancestry (14,671 cases and 17,667 controls) as a discovery stage, identifying 14 significant candidate variant-variant interactions. We then used four independent cohorts (13,377 cases and 413,789 controls) as replication stage, successfully replicating three epistasis signals located nearby SNCA and within MAPT and WNT3. Admixture analysis showed that the epistatic effect on PD of those variants at these loci was observed in both European ancestry and Native American ancestry individuals. We assessed the functional impact of the epistasis signals across a range of functional/-omics datasets identifying significant single-variant eQTLs across brain tissues, epistasis eQTL signals in whole-blood, PD-relevant pathways and ontologies, and chromatin interactions between the regions of the interacting SNPs.
In conclusion, we identified and replicated novel epistatic signals associated with PD risk across multiple diverse genetic ancestry cohorts, highlighting their enrichment in pathways relevant to Parkinson’s disease.
Evaluating multiple sclerosis severity loci 30 years after a clinically isolated syndrome
Authors: Sahi Nitin , Haider Lukas , Chung Karen , Prados Carrasco Ferran , Kanber Baris , Samson Rebecca , Thompson Alan J , Trip S Anand , Brownlee Wallace , Ciccarelli Olga , Barkhof Frederik , Tur Carmen , Houlden Henry , Chard Declan 
Published: December 2024

Abstract
The first genome-wide significant multiple sclerosis severity locus, rs10191329, has been pathologically linked to cortical lesion load and brain atrophy. However, observational cohorts such as MSBase have not replicated associations with disability outcomes, instead finding other loci. We evaluated rs10191329 and MSBase loci in a unique cohort of 53 people followed for 30 years after a clinically isolated syndrome, with deep clinical phenotyping and MRI measures of inflammation and neurodegeneration. After 30 years, 26 had developed relapsing-remitting multiple sclerosis, 15 secondary progressive multiple sclerosis and 12 remained diagnosed with a clinically isolated syndrome. Genetic associations with disease severity (age-related multiple sclerosis severity score and Expanded Disability Status Scale), disease course and brain MRI features (white matter lesions, cortical lesions and grey matter fraction) were investigated using regression models and survival analyses. rs10191329 was not associated with multiple sclerosis severity, secondary progressive multiple sclerosis diagnosis or brain MRI features at 30 years. Similarly, MSBase loci were not associated with 30-year disease severity, although rs73091975 was significantly associated with lower 14-year age-related multiple sclerosis severity score in those developing multiple sclerosis. Given that effect sizes for both rs10191329 and rs73091975 were greatest between 14 and 20 years, these findings suggest genetic effects on multiple sclerosis severity may interact non-linearly with disease duration.
Shared decision-making in central centrifugal cicatricial alopecia
Authors: Swain Elizabeth , Haughton Renee , Palmer Victoria , Obeime Ivie , McMichael Amy 
Published: December 2024

Abstract
Central centrifugal cicatricial alopecia (CCCA) is a primary lymphocytic scarring alopecia, which predominantly occurs in middle-aged Black women. The benefits and use of shared decision-making (SDM) models in patients with CCCA have yet to be studied. We conducted a cross-sectional survey to investigate the role of SDM in the management of CCCA. SDM processes were evaluated using the nine-item Shared Decision-Making Questionnaire (SDM-Q-9), the Decisional Regret Scale (DRS) and the Control Preferences Scale (CPS). Between June and August 2023, members of the Scarring Alopecia Foundation were emailed and invited to participate; n = 87/1192 members responded. The CPS responses suggested that most patients (48%, n = 41/87) preferred to share responsibility with their doctor for treatment decisions. The SDM-Q-9 (scored 0–45) and DRS (scored 0–100) demonstrated mean (SD) scores of 27.5 (11.5) and 38.4 (19.4), with higher and lower scores, respectively, demonstrating greater patient satisfaction with SDM. SDM is useful for patients involved in complex decision-making when several medically reasonable treatment alternatives are available. Patients with CCCA may benefit from this model, and investment in resources such as patient decision aids and SDM training for dermatologists will aid integration into clinical practice. Together, the CPS, DRS and SDM-Q-9 results suggested that patients with CCCA preferred to be involved in their treatment management decisions, regardless of their sociodemographic characteristics.
Identification and characterization of human KALRN mRNA and Kalirin protein isoforms
Authors: Mould Arne W , Wright David J , Bornemann Klaus D , Hengerer Bastian , Pinnock Rob , Drydale Edward , Bancroft James , Hall Nicola A L , von Delft Annette , Brennan Paul E , Harrison Paul J , Haerty Wilfried , Tunbridge Elizabeth M 
Published: December 2024

Abstract
Kalirin is a multidomain protein with important roles in neurite outgrowth, and synaptic spine formation and remodeling. Genetic and pathophysiological links with various neuropsychiatric disorders associated with synaptic dysfunction and cognitive impairment have sparked interest in its potential as a pharmacological target. Multiple Kalirin proteoforms are detected in the adult human brain, yet we know little about the diversity of the transcripts that encode them or their tissue profiles. Here, we characterized full-length KALRN transcripts expressed in the adult human frontal lobe and hippocampus using rapid amplification of complementary DNA (cDNA) ends and nanopore long-read sequencing. For comparison with non-neural tissue, we also analyzed KALRN transcripts in the aorta. Multiple novel isoforms were identified and were largely similar between the two brain regions analyzed. Alternative splicing in the brain results in preferential inclusion of exon 37, which encodes 32 amino acids upstream of the second guanine nucleotide exchange factor (GEF) domain. Structural modeling predicts that a subset of these amino acids forms a conserved alpha helix. Although deletion of these amino acids had little effect on GEF activity, it did alter Kalirin-induced neurite outgrowth suggesting that this brain-enriched splicing event may be important for neural function. These data indicate that alternative splicing is potentially important for regulating Kalirin actions in the human brain.
Difference in spin structure of magnetic metal-organic frameworks between cluster model and periodic system
Authors: Amamizu Naoka , Tada Kohei , Kishi Ryohei , Kosaka Wataru , Miyasaka Hitoshi , Kitagawa Yasutaka 
Published: December 2024

Abstract
We compare the calculated spin structures of magnetic metal-organic frameworks consisting of paddlewheel-type diruthenium complexes and tetracyano-p-quinodimethane derivatives using density functional theory calculations with Gaussian basis sets and DFT + U/plane-wave calculations under periodic conditions. The calculated results indicate that the asymmetricity of the spin density inside the [Ru2] unit disappears in the periodic systems. In addition, based on the partial spin density analysis, the electron conductivity would be switchable by changing the spin states of the metal-organic frameworks.
Influenza Vaccine Effectiveness Against Hospitalizations and Emergency Department or Urgent Care Encounters for Children, Adolescents, and Adults During the 2023–2024 Season, United States
Authors: Tenforde Mark W , Reeves Emily L , Weber Zachary A , Tartof Sara Y , Klein Nicola P , Dascomb Kristin , DeSilva Malini B , Yang Duck-Hye , Grannis Shaun J , Irving Stephanie A , Ong Toan C , Link-Gelles Ruth , Salas S Bianca , Sy Lina S , Lewin Bruno , Contreras Richard , Zerbo Ousseny , Fireman Bruce , Hansen John , Timbol Julius , Sheffield Tamara , Bride Daniel , Arndorfer Julie , VanOtterloo Josh , McEvoy Charlene E , Akinsete Omobosola O , Essien Inih J , Dixon Brian E , Rogerson Colin , Fadel William F , Duszynski Thomas , Naleway Allison L , Barron Michelle A , Rao Suchitra , Mayer David , Chavez Catia , Ball Sarah W , Payne Amanda B , Ray Caitlin , Dickerson Monica , Neelam Varsha , Adams Katherine , Flannery Brendan , DeCuir Jennifer , Garg Shikha 
Published: December 2024

Abstract

Background
The 2023–2024 influenza season had predominant influenza A(H1N1)pdm09 virus activity, but A(H3N2) and B viruses cocirculated. Seasonal influenza vaccine strains were well-matched to these viruses.

Methods
Using healthcare encounters data from health systems in 8 US states, we evaluated influenza vaccine effectiveness (VE) against influenza-associated medical encounters from October 2023 to April 2024. Using a test-negative design, we compared the odds of vaccination between patients with an acute respiratory illness who tested positive (cases) versus negative (controls) for influenza by molecular assay, adjusting for confounders. VE was stratified by age group, influenza type (overall, influenza A, influenza B), and care setting (hospitalization, emergency department or urgent care [ED/UC] encounter).

Results
Overall, 74 000 encounters in children and adolescents aged 6 months–17 years (3479 hospitalizations, 70 521 ED/UC encounters) and 267 606 in adults aged ≥18 years (66 828 hospitalizations, 200 778 ED/UC encounters) were included. Across care settings, among children and adolescents, 15% (2758/17 833) of cases versus 32% (18 240/56 167) of controls had received vaccination. Among adults, 25% (11 632/46 614) of cases versus 44% (97 811/220 992) of controls across care settings had received vaccination. VE was 58% (95% confidence interval [95% CI], 44–69) against hospitalization and 58% (95% CI, 56–60) against ED/UC encounters for children and adolescents, and 39% (95% CI, 35–43) against hospitalization and 47% (95% CI, 46–49) against ED/UC encounters for adults. Across age groups, VE was higher against influenza B than influenza A.

Conclusions
Influenza vaccines provided protection against influenza-associated illness across health care settings and age groups during the 2023–2024 influenza season.
Efficacy and safety of dapagliflozin in patients with CKD: real-world experience in 93 Italian renal clinics
Authors: Minutolo Roberto , Borrelli Silvio , Ambrosini Andrea , Amoroso Luigi , Aucella Filippo , Batini Valentina , Battaglia Yuri , Bregoli Laura , Cantaluppi Vincenzo , Cianciolo Giuseppe , Conti Paolo , Fabbrini Paolo , Giammarresi Carlo , Imbalzano Egidio , La Rosa Sandra , Marengo Marita , Montinaro Vincenzo , Musone Dario , Napoli Marcello , Nappi Felice , Pluvio Corrado , Santoro Domenico , Scarpioni Roberto , Sopranzi Franco , Tullio Tiziana , De Nicola Luca 
Published: December 2024

ABSTRACT

Background
Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are recommended for reducing the renal and cardiovascular risk in patients with chronic kidney disease (CKD) based on the positive results reported by clinical trials. However, real-world data on the efficacy and the safety of these drugs in CKD population followed in nephrology setting are lacking.

Methods
We report the effects of dapagliflozin in CKD patients by using data collected during a learning program in which 105 nephrologists added dapagliflozin (10 mg/day) to consecutive patients referred to their renal clinics. Efficacy endpoints were the albuminuria change and the determinants of an albuminuria decline ≥30%. Adverse events were also collected.

Results
A total of 1724 patients with CKD (age 67.4 ± 13.2 years, 72.8% males, diabetes 59.9%, eGFR 43.5 ± 17.4 ml/min/1.73 m2, severe albuminuria 70.1%) received dapagliflozin for 4 ± 1 months. Dapagliflozin significantly reduced body weight (−1.3 kg), eGFR (−0.27 ml/min/month), and blood pressure (−3.6/−1.7 mmHg). Albuminuria declined by 25.1% (95%CI 23.0–27.2) from 500 mg/day [IQR 225–1425] to 320 mg/day [IQR 100–900]. Albuminuria reduction was ≥30% in 48.3% of patients, 0–29% in 37.6% while it increased in 14.1% of patients. At logistic regression analysis, older age, female sex, use of mineralocorticoid receptor antagonist, higher eGFR, and higher albuminuria were all significant predictors of albuminuria decline ≥30%. We collected 46 side effects leading to drug discontinuation in 36 patients (2%), with acute kidney injury and urinary tract infection being the most frequent adverse events.

Conclusions
We provide evidence of the anti-proteinuric efficacy of short-term dapagliflozin in the presence of good safety profile in patients with CKD followed in nephrology.
Multilevel Factors and Sleep in Adults With Inflammatory Bowel Disease: A Qualitative Study
Authors: Winders Samantha , Yoo Linda , Heitkemper Margaret , Kamp Kendra 
Published: December 2024

Abstract

Background
This study aimed to describe the patient-reported factors that impact sleep among individuals with inflammatory bowel disease (IBD), aligning with the Social Ecological Model of Sleep. This addresses the gap in IBD sleep research, which predominantly focuses on individual-level factors and their impact on sleep.

Methods
Adults (ages 18-65) with IBD were recruited online through ResearchMatch in June 2023. Participants filled out survey questions on their demographic characteristics, health history, sleep, and IBD-related symptoms. Content analysis was conducted on 2 open-ended questions about factors that impacted their sleep.

Results
This analysis included 163 adults with IBD (M = 39 years of age, 76.7% White, 91.4% non-Hispanic or Latino, 66.9% female, and 83.4% active IBD) who answered open-ended questions with comments about their sleep. Most participants indicated an individual-level factor impacted their sleep quality (85.3%, n = 139), categorized into 5 subthemes: Mental health, health, behavior and choices, physiology, and attitudes. Additionally, participants (43.6%, n = 71) mentioned social-level factors divided into 7 subthemes: Family, work, home, neighborhood, social network, and school. A smaller group of participants (17.2%, n = 28) mentioned societal-level factors designated into 4 subthemes: Natural environment and geography, technology, 24/7 society, and economics.

Conclusions
This study highlights the need for tailored sleep interventions for those with IBD that consider not only disease activity but also mental health, family, work, and the natural environment. IBD clinics should prioritize sleep health using an interdisciplinary approach to holistically address the unique needs of those with IBD.
Diffusion-weighted imaging of the head and neck: comparison between integrated slice-specific dynamic shimming and simultaneous multi-slice readout-segmented echo-planar sequences
Authors: Su Tong , Zhu Xiaoli , Chen Yu , Xu Zhentan , Chen Xingming , Zhang Tao , Zhu Jinxia , Liu Wei , Wang Xiaoye , Zhang Zhuhua , Feng Feng , Jin Zhengyu 
Published: December 2024

Abstract

Objectives
To compare integrated slice-specific dynamic shimming (iShim) and simultaneous multi-slice (SMS) readout-segmented echo-planar imaging (RESOLVE) for diffusion-weighted imaging (DWI) of malignant head and neck tumours.

Methods
In this prospective study, 45 patients with malignant head and neck lesions underwent iShim- and SMS-RESOLVE imaging with two b-values (0, 800 s/mm2) at 3 T. Subjective image quality scores (lesion distortion, signal loss, fat saturation, and artefacts), quantitative lesion distortion, quantitative image quality [signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and SNR efficiency], ADC values, and total acquisition times of iShim- and SMS-RESOLVE imaging were evaluated and compared.

Results
iShim-RESOLVE (3 mins 7 s) had longer acquisition times than SMS-RESOLVE (2 min 1 s). iShim-RESOLVE images had much better overall image quality, geometric distortion, fat saturation, and signal loss than SMS-RESOLVE (P &lt; .05). The quantitative tumour distortion in iShim-RESOLVE images was significantly smaller than those of SMS-RESOLVE, measured either with b = 0 s/mm2 or b = 800 s/mm2 (P &lt; .05). Using the iShim technique, the SNR, CNR of high b-value images, and SNR efficiency were significantly higher than those of SMS-RESOLVE (P &lt; .001). The ADC measurements with excellent agreement of iShim-RESOLVE images were higher than those of SMS-RESOLVE.

Conclusions
iShim-RESOLVE can decrease lesion distortion and improve overall image quality compared with SMS-RESOLVE in head and neck region.

Advances in knowledge
iShim-RESOLVE DWI may serve as a promising technique for reducing distortion and assessing head and neck lesions in clinical practice.
Detection of periodontal bone loss and periodontitis from 2D dental radiographs via machine learning and deep learning: systematic review employing APPRAISE-AI and meta-analysis
Authors: Khubrani Yahia H , Thomas David , Slator Paddy J , White Richard D , Farnell Damian J J 
Published: December 2024

Abstract

Objectives
Periodontitis is a serious periodontal infection that damages the soft tissues and bone around teeth and is linked to systemic conditions. Accurate diagnosis and staging, complemented by radiographic evaluation, are vital. This systematic review (PROSPERO ID: CRD42023480552) explores artificial intelligence (AI) applications in assessing alveolar bone loss and periodontitis on dental panoramic and periapical radiographs

Methods
Five databases (Medline, Embase, Scopus, Web of Science, and Cochrane’s Library) were searched from January 1990 to January 2024. Keywords related to “artificial intelligence”, “Periodontal bone loss/Periodontitis”, and “Dental radiographs” were used. Risk of bias and quality assessment of included papers were performed according to the APPRAISE-AI Tool for Quantitative Evaluation of AI Studies for Clinical Decision Support. Meta analysis was carried out via the “metaprop” command in R V3.6.1.

Results
Thirty articles were included in the review, where 10 papers were eligible for meta-analysis. Based on quality scores from the APPRAISE-AI critical appraisal tool of the 30 papers, 1 (3.3%) were of very low quality (score &lt; 40), 3 (10.0%) were of low quality (40 ≤ score &lt; 50), 19 (63.3%) were of intermediate quality (50 ≤ score &lt; 60), and 7 (23.3%) were of high quality (60 ≤ score &lt; 80). No papers were of very high quality (score ≥ 80). Meta-analysis indicated that model performance was generally good, eg, sensitivity 87% (95% CI, 80%-93%), specificity 76% (95% CI, 69%-81%), and accuracy 84% (95% CI, 75%-91%).

Conclusion
Deep learning shows much promise in evaluating periodontal bone levels, although there was some variation in performance. AI studies can lack transparency and reporting standards could be improved. Our systematic review critically assesses the application of deep learning models in detecting alveolar bone loss on dental radiographs using the APPRAISE-AI tool, highlighting their efficacy and identifying areas for improvement, thus advancing the practice of clinical radiology.
Healthcare deservingness: how risk factors and income shape responsibility attribution for health outcomes and healthcare costs
Authors: Baute Sharon , Bellani Luna 
Published: December 2024

Abstract
Amidst the global surge in healthcare expenditures, there is a growing political and academic debate about individual versus collective responsibility for health and healthcare costs. This study explores the causal effects of health risks and income cues on citizens’ attribution of responsibility for health outcomes and healthcare costs. An original vignette experiment was conducted among the German population. Those in need of medical treatment who have been exposed to environmental, institutional, or biological health risks are held less responsible for their health outcomes than those exhibiting behavioural health risks. However, the impact of health risks appears to be somewhat weaker in determining who should bear the costs for the medical treatment. Furthermore, higher-income groups are more likely to be blamed for their health outcomes and are considered less deserving of society’s help in paying for medical treatment. These findings enhance our understanding of how the criteria of control and economic need shape public attribution of responsibility in the health(care) domain.
Genome-wide screen overexpressing mycobacteriophage Amelie genes identifies multiple inhibitors of mycobacterial growth
Authors: Tafoya Chelsea , Ching Brandon , Garcia Elva , Lee Alyssa , Acevedo Melissa , Bass Kelsey , Chau Elizabeth , Lin Heidi , Mamora Kaitlyn , Reeves Michael , Vaca Madyllyne , van Iderstein William , Velasco Luis , Williams Vivianna , Yonemoto Grant , Yonemoto Tyler , Heller Danielle M , Diaz Arturo 
Published: December 2024

Abstract
The genome sequences of thousands of bacteriophages have been determined and functions for many of the encoded genes have been assigned based on homology to characterized sequences. However, functions have not been assigned to more than two-thirds of the identified phage genes as they have no recognizable sequence features. Recent genome-wide overexpression screens have begun to identify bacteriophage genes that encode proteins that reduce or inhibit bacterial growth. This study describes the construction of a plasmid-based overexpression library of 76 genes encoded by Cluster K1 mycobacteriophage Amelie, which is genetically similar to cluster K phages Waterfoul and Hammy recently described in similar screens and closely related to phages that infect clinically important mycobacteria. Twenty-six out of the 76 genes evaluated in our screen, encompassing 34% of the genome, reduced growth of the host Mycobacterium smegmatis to various degrees. More than one-third of these 26 toxic genes have no known function, and 10 of the 26 genes almost completely abolished host growth upon overexpression. Notably, while several of the toxic genes identified in Amelie shared homologs with other Cluster K phages recently screened, this study uncovered 7 previously unknown gene families that exhibit cytotoxic properties, thereby broadening the repertoire of known phage-encoded growth inhibitors. This work, carried out under the HHMI-supported SEA-GENES project (Science Education Alliance Gene-function Exploration by a Network of Emerging Scientists), underscores the importance of comprehensive overexpression screens in elucidating genome-wide patterns of phage gene function and novel interactions between phages and their hosts.