bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic neurodevelopmental clustering and dyslexia
Authors: Ciulkinyte Austeja , Mountford Hayley S , Fontanillas Pierre ,   23andMe Research Team, Bates Timothy C , Martin Nicholas G , Fisher Simon E , Luciano Michelle 
Published: October 2023

AbstractDyslexia is a learning difficulty with neurodevelopmental origins, manifesting as reduced accuracy and speed in reading and spelling despite adequate education. Dyslexia is substantially heritable and frequently co-occurs with other neurodevelopmental conditions, particularly attention deficit-hyperactivity disorder (ADHD). The purpose of this paper was to elucidate how genetic factors predisposing to dyslexia correlate with risk for other neurodevelopmental and psychiatric traits. A large-scale genome-wide association study (GWAS) of dyslexia diagnosis self-report (51,800 cases and ∼1.1 million controls), together with GWAS of ADHD, autism, Tourette syndrome, anxiety, depression, schizophrenia, bipolar, obsessive compulsive disorder, anorexia, were analysed using Genomic Structural Equation Modelling (GenomicSEM) to construct a genomic structural model. The final model consisted of five correlated latent genomic factors described as F1) internalising disorders, F2) psychotic disorders, F3) compulsive disorders, F4) neurodevelopmental conditions, and F5) attention and learning difficulties, which includes ADHD and dyslexia. This latent factor was moderately correlated with internalising disorders (.40) and, to a lesser extent, with neurodevelopmental conditions (.25) and psychotic disorders (.17), and negatively with compulsive disorders (-.16). Unlike ADHD, most of the genomic variance in dyslexia was unique, suggesting a more peripheral relation to psychiatric traits. We further investigated genetic variants underlying both dyslexia and ADHD. This implicated 49 loci (40 of which were not reported in GWAS of the individual traits) mapping to 174 genes (121 not found in GWAS of individual traits). Our study has discovered novel pleiotropic variants and confirms via GenomicSEM the heightened genetic relation between dyslexia and ADHD versus other psychiatric traits. In future, analyses including additional co-occurring traits such as dyscalculia and dyspraxia, for which there are currently no large-scale GWAS, will allow a more clear definition of the attention and learning difficulties genomic factor, yielding further insights into factor structure and pleiotropic effects.
GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets
Authors: Dand Nick , Stuart Philip E , Bowes John , Ellinghaus David , Nititham Joanne , Saklatvala Jake R , Teder-Laving Maris , Thomas Laurent F , Traks Tanel , Uebe Steffen , Assmann Gunter , Baudry David , Behrens Frank , Billi Allison C , Brown Matthew A , Burkhardt Harald , Capon Francesca , Chung Raymond , Curtis Charles J , Duckworth Michael , Ellinghaus Eva , FitzGerald Oliver , Gerdes Sascha , Griffiths Christopher E M , Gulliver Susanne , Helliwell Philip , Ho Pauline , Hoffmann Per , Holmen Oddgeir L , Huang Zhi-ming , Hveem Kristian , Jadon Deepak , Köhm Michaela , Kraus Cornelia , Lamacchia Céline , Lee Sang Hyuck , Ma Feiyang , Mahil Satveer K , McHugh Neil , McManus Ross , Modalsli Ellen H , Nissen Michael J , Nöthen Markus , Oji Vinzenz , Oksenberg Jorge R , Patrick Matthew T , Perez-White Bethany E , Ramming Andreas , Rech Jürgen , Rosen Cheryl , Sarkar Mrinal K , Schett Georg , Schmidt Börge , Tejasvi Trilokraj , Traupe Heiko , Voorhees John J , Wacker Eike Matthias , Warren Richard B , Wasikowski Rachael , Weidinger Stephan , Wen Xiaoquan , Zhang Zhaolin ,   BSTOP study group,   Estonian Biobank research team, Barton Anne , Chandran Vinod , Esko Tõnu , Foerster John , Franke Andre , Gladman Dafna D , Gudjonsson Johann E , Gulliver Wayne , Hüffmeier Ulrike , Kingo Külli , Kõks Sulev , Liao Wilson , Løset Mari , Mägi Reedik , Nair Rajan P , Rahman Proton , Reis André , Smith Catherine H , Meglio Paola Di , Barker Jonathan N , Tsoi Lam C , Simpson Michael A , Elder James T 
Published: October 2023

AbstractPsoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci. To move towards a saturation map of psoriasis susceptibility we meta-analysed 18 GWAS comprising 36,466 cases and 458,078 controls and identified 109 distinct psoriasis susceptibility loci, including 45 that have not been previously reported. These include susceptibility variants at loci in which the therapeutic targets IL17RA and AHR are encoded, and deleterious coding variants supporting potential new drug targets (including inSTAP2,CPVLandPOU2F3). We conducted a transcriptome-wide association study to identify regulatory effects of psoriasis susceptibility variants and cross-referenced these against single cell expression profiles in psoriasis-affected skin, highlighting roles for the transcriptional regulation of haematopoietic cell development and epigenetic modulation of interferon signalling in psoriasis pathobiology.
Use of Probiotics in the Prevention of Clostridioides difficile Infections during Antibiotic Exposure: A Systematic Review and Meta-Analysis
Authors: Dabrowski Veronica 
Published: October 2023

AbstractClostridioides difficileinfections are a growing concern in the hospital setting. Current prevention methods include infection control strategies, antibiotic stewardship, and proper hand hygiene. However, the occurrence ofC. difficilestill manages to cause nosocomial outbreaks especially in vulnerable populations. Probiotics have been historically questioned for their use in the prevention of antibiotic-associated diarrhea and more specifically,C. difficileinfections.This meta-analysis pools 10 randomized controlled trials for the prevention ofClostridioides difficileinfections (CDI) from reviewing the Cochrane Central Register of Controlled Trials (CENTRAL).A prioriinclusion criteria remained as follows: RCTs, blinded/open trials, all populations, articles, or conference abstracts. Exclusion criteria excluded publications published outside 2013-2023*, non-English language trials, pre-clinical trials/protocols, case reports/series/systematic reviews, duplicates, probiotics not specified in methods, non-RCTs, incomplete/no outcomes reported, no confirmation ofClostridioides difficileinfection. Probiotic strains tested in these trials mainly includedLactobacillus spp. and Bifidobacterium spp. Some studies showed significant benefits while others did not find significant improvement in the prevention ofC. difficileinfections.The meta-analysis suggests that probiotics may have a positive effect in preventing CDI during antibiotic treatment. The study results had large levels of statistical heterogeneity which indicates an argument for further large-scale research to provide more definitive evidence on the efficacy of probiotics in CDI prevention.
Development and validation of a nomogram for predicting overall survival of patients with ischemic cardiomyopathy and heart failure: a post-hoc analysis of the Surgical Treatments for Ischemic Heart Failure (STICH) trail
Authors: Guo Pengju , He Chang , Li Junlei , Jiang Youxu , Wang Feng , Wang Jiaxiang , Lin Bin , Feng Deguang 
Published: October 2023

AbstractPurposeTo establish a nomogram for predicting the overall survival (OS) of patients with ischemic cardiomyopathy and heart failure based on the Surgical Treatment for Ischemic Heart Failure (STICH) trail.MethodsPatients who had valid key variables in the hypothesis 1 were included and randomly divided into the training and validation groups (7:3 ratio). Using Cox proportional hazards model, predictors for the OS in training group were identified and integrated to establish a nomogram for predicting 1-year, 3-year, 5-year, and ten-year survival probability. The nomogram performance was evaluated using Harrell’s concordance index (C-index), time-dependent receiver operating characteristic curve, decision curve analysis, and Kaplan-Meier survival analysis.Results940 of 1212 patients who had valid key variables were included. Seven predictors, including treatment type, gender, estimated glomerular filtration rate, Charlson co-morbidity index, 6-minute walk, end-systolic volume index and mitral regurgitation class were identified to establish the nomogram. The C-indices of the nomogram were 0.641 (95% CI: 0.627-0.655) and 0.649 (95% CI: 0.627-0.671) for training and validation groups, respectively. The calibration curves revealed consistency between predicted and observed survival. The area under 1-year, 3-year, 5-year, and ten-year OS receiver operating characteristic curves were 0.634, 0.616, 0.630 and 0.638 in the training group, respectively. Decision curve analysis showed effective net benefits of the model in clinical decision-making. Divided by the cutoff values of prognostic indices, low-risk patients showed better OS than those with high risk in training and validation groups (both p < 0.0001).ConclusionThe current nomogram can effectively predict the OS of patients with ischemic cardiomyopathy and heart failure, provide information about multidisciplinary therapeutic that may prolong the survival time, and serve as a perfect tool in conjunction with the STS and EuroSCORE II risk models in clinical decision making.
Characteristic variables of acute ischemic stroke categorized according to body mass index classifications
Authors: Senda Joe , Amakusa Yoshinobu , Hirunagi Tomoki , Ida Ruido , Muro Hidenori , Otani Takahito , Nakagawa-Senda Hiroko , Naito Takehiro , Kato Takenori , Hasegawa Toshinori , Kawaguchi Katsuhiro , Katsuno Masahisa 
Published: October 2023

AbstractBACKGROUNNDWe investigated the characteristic variables of acute ischemic stroke categorized according to body mass index (BMI).METHODSFrom a registry of 1676 consecutive acute ischemic stroke cases, 965 cases (622 men and 434 women; mean age 71.53 ± 12.42 years) were selected based on eligibility criteria. These participants were divided into four cohorts according to BMI classifications: BMI < 18 (underweight), 18.5 ≤ BMI < 25 (normal weight), 25 ≤ BMI < 30 (overweight), and BMI ≥ 30 (obese). To avoid bias, propensity score analyses were performed; the confounding variables of sex and age were adjusted.RESULTSThe underweight cohort (n = 82) had an older, largely female population. The overweight (n = 212) and obese cohorts (n = 48) had younger populations. The analyses revealed no significant differences in neurological outcomes among the four cohorts. Furthermore, higher risks of hyperlipidemia, dyslipidemia, and diabetes mellitus were associated with the higher BMI cohorts in participants with acute ischemic stroke. Findings revealed higher rates of usage of antidiabetic and antidyslipidemic medications in the overweight cohort (p = 0.007, p = 0.003; respectively) and raised values of triglycerides, low-density lipoprotein cholesterol, and glycated hemoglobin in the obese cohort (p = 0.044, p = 0.019, p < 0.001; respectively) than in the normal weight cohort. By contrast, the lower BMI cohort (underweight) did not have hyperlipidemia.CONCLUSIONSThe importance of focusing on the management of dyslipidemia, hyperlipidemia, and hyperglycemia for acute ischemic stroke in patients who are overweight or obese has been highlighted.
The molecular basis of Abelson kinase regulation by its αI-helix
Authors: Paladini Johannes , Maier Annalena , Habazettl Judith Maria , Hertel Ines , Sonti Rajesh , Grzesiek Stephan 
Published: October 2023

AbstractAbelson tyrosine kinase (Abl) is regulated by the arrangement of its regulatory core, consisting sequentially of the SH3, SH2 and kinase (KD) domains, where an assembled or disassembled core corresponds to low or high kinase activity, respectively. It was recently established that binding of type II ATP site inhibitors, such as imatinib, generates a force from the KD N-lobe onto the SH3 domain and in consequence disassembles the core. Here, we demonstrate that the C-terminal αI-helix exerts an additional force towards the SH2 domain, which correlates both with kinase activity and type II inhibitor-induced disassembly. The αI- helix mutation E528K, which is responsible for the ABL1 malformation syndrome, strongly activates Abl by breaking a salt bridge with the KD C-lobe and thereby increasing the force onto the SH2 domain. In contrast, the allosteric inhibitor asciminib strongly reduces Abl’s activity by fixating the αI-helix and reducing the force onto the SH2 domain. These observations are explained by a simple mechanical model of Abl activation involving forces from the KD N-lobe and the αI-helix onto the KD/SH2SH3 interface.
How long is long? Word length effects in reading correspond to minimal graphemic units: An MEG study in Bangla
Authors: Moitra Swarnendu , Chacón Dustin A. , Stockall Linnaea 
Published: October 2023

AbstractThis paper presents a magnetoencephalography (MEG) study on reading in Bangla, an east Indo-Aryan language predominantly written in an abugida script. The study aims to uncover how visual stimuli are processed and mapped onto abstract linguistic representations in the brain. Specifically, we investigate the neural responses that correspond to word length in Bangla, a language with a unique orthography that introduces multiple ways to measure word length. Our results show that MEG signals localised in the anterior left fusiform gyrus, at around 130ms, are highly correlated with word length when measured in terms of the number of minimal graphemic units in the word rather than independent graphemic units (akśar) or phonemes. Our findings suggest that minimal graphemic units could serve as a suitable metric for measuring word length in non-alphabetic orthographies such as Bangla.
Early delta cortical tracking to non-verbal auditory stimuli predicts reading skills: A one-year longitudinal study
Authors: Zugarramurdi Camila , Fernández Lucía , Lallier Marie , Valle-Lisboa Juan Carlos , Carreiras Manuel 
Published: October 2023

AbstractThe precision of cortical tracking of auditory rhythmic stimuli in low frequency ranges coding for prosodic (delta) and syllabic (theta) amplitude modulations in the speech signal has been proposed to contribute to the development of phonological processing and reading acquisition. The present study investigates the role of low frequency cortical tracking of non-verbal auditory stimuli in reading acquisition through a longitudinal design from before the onset of formal reading instruction until one year afterwards. At time one, 40 prereading children performed a passive listening task of amplitude modulated white noise presented in the delta (2 Hz) and theta (4 Hz) frequency bands, while their neural activity was recorded via EEG. At time two, at the end of first grade, children’s reading skills were assessed. Results show significant cortical tracking in prereading children at both frequencies, with larger responses for theta than for delta rate non-verbal auditory stimuli. Importantly, only pre-reding cortical tracking measures for delta rate stimuli predicted reading acquisition one year later. These findings underscore the role of early neural synchronization to delta rate rhythmic auditory stimuli to reading acquisition and support the potential important role of early prosodic processing for the development of future reading skills.
Introduction of Dicistrovirus IRESs into UAS/SV40-polyA constructs results in premature polyadenylation and strong overexpression of the upstream ORF inDrosophilaanimals
Authors: Lidsky Peter V. , Dmitriev Sergey E. , Andino Raul 
Published: October 2023

AbstractTo evaluate the properties of insect virus internal ribosomal entry sites (IRESs) for protein expression inDrosophila, we have introduced Cricket Paralysis virus (CrPV) and Drosophila C virus (DCV) IRESs into UAS/SV40-polyA vector. We found that introduction of IRESs induce premature polyadenylation, resulting in both truncation of the mRNA, and an increase in mRNA levels of approximately 40-fold. The increase in mRNA levels was accompanied by increased resistance to nonsense-mediated mRNA decay (NMD)-mediated degradation. Our results suggest that premature polyadenylation increases mRNA stability in the SV40 polyadenylation site-containing constructs, suggesting a novel method for robust overexpression of transgenes inDrosophila.
A novelin vivosystem to study coral biomineralization in the starlet sea anemone (Nematostella vectensis)
Authors: Foster Brent , Hugosson Fredrik , Scucchia Federica , Enjolras Camille , Babonis Leslie , Hoaen Will , Martindale Mark Q. 
Published: October 2023

AbstractCoral reefs are important for maintaining healthy marine ecosystems and are declining rapidly due to increasing environmental stresses. Coral conservation efforts require a mechanistic understanding of how these stresses may disrupt biomineralization, but progress in this area has been slow primarily because corals are not easily amenable to laboratory research. Some cellular characteristics of biomineralization are well characterized, such as the role of carbonic anhydrases, the polarized secretion of ions, and the secretion of “intrinsically disordered proteins” (IDPs) into extracellular microenvironments. We highlight how the starlet sea anemone (Nematostella vectensis) can serve as a tractable model to interrogate the cellular mechanisms of coral biomineralization. We have developed transgenic constructs using genes involved in biomineralization from several animal phyla that can be injected intoNematostellazygotes. These constructs are designed so translated proteins may be purified using TEV protease or Histidine tags to study their physicochemical properties. Using a fluorescent tag, we confirm ectopic expression of the coral biomineralizing protein SpCARP1 in liveNematostellaembryos and adults and demonstrate via calcein staining that calcium ions co-localize with SpCARP1 in carbonate and calcium enriched seawater. Our findings suggest that SpCARP1 can induce the formation of amorphous calcium carbonate precursors inN. vectensis, consistent with its suspected role in the early stages of coral biomineralization. These results lay a fundamental groundwork for establishingN. vectensisas a novelin vivosystem to explore the evolutionary and cellular mechanisms of biomineralization, improve coral conservation efforts, and even develop novel biomaterials.Graphical Abstract
HIV-HBV Co-infections in Central India: Prevalence, Clearance Rates, and Long-term Outcomes from a Decade of Experience at a Tertiary Care Center
Authors: Kunkal Uppal Rashmi , Mishra Nitu , Tiwari Jyoti , Saad Talha , Vyas Ashish Kumar , Rai Amardeep , Rawat Sumit K 
Published: October 2023

AbstractTwo of the most infamous viruses, the Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) have similar transmission routes. Consequently, some individuals might get co-infected with both viruses resulting in increased deaths and prolonged disease. Even among healthy (Non-immunocompromised) persons, chances of getting persistent HBV infection are 5-10%, however among persons harboring HIV, HBV the persistence rates might escalate up to 15 %. Such increased suffering might occur despite the longevity provided by starting highly active anti-retroviral therapy (HAART), which is the current standard treatment.Our pioneering study, in our region aims to assess the prevalence of HIV-HBV co-infection, clearance rates of HBV, demographic characteristics of affected individuals, and long-term outcomes. By shedding light on these aspects, we hope to gain valuable insights into the impact of such co-infections and pave the way for better management and care of individuals facing this dual challenge.We studied 1808 persons enrolled for HIV treatment from amongst 170,019 persons screened. Higher co-infection of HIV-HBV was observed in males as compared to females, with the age group of 31-40 years being most affected. The most common route of infection, was heterosexual contact accounting for 86% of cases, accounting for majority co-infections. Over the years, we noticed a decline in the number of HIV-HBV co-infected cases, with the nadir occurring in 2015. Seroprevalence of co-infections was 2.37%, but despite this observed low sero-prevalence HBV clearance was relatively poor among the co-infected, as only 4 (9.3%) able to clear the infection after initiation of HAART. Our study highlights that chances of HBV clearance among the co-infected are worse than that observed among otherwise heathy populations thus also highlighting the urgent need for universal HBV vaccination in all HIV-affected persons, underscoring the importance of providing special attention to them.
Glaucoma medication adherence and associated factors among adult glaucoma patients in Ethiopia: A systematic review and meta-analysis
Authors: Abore Kibruyisfaw Weldeab , Fole Estifanos Bekele , Abebe Mahlet Tesfaye , Tekle Natnael Fikadu , Tilahun Robel Bayou , Chinkey Fraol Daba , Abera Michael Teklehaimanot 
Published: October 2023

AbstractBackgroundGlaucoma medications are one important pillar of glaucoma management to control intraocular pressure. If left uncontrolled, intraocular pressure causes progressive visual loss and blindness. Thus, adherence to glaucoma medication is vital to prevent optic nerve damage and its consequences. This study was conducted to systematically summarize the magnitude of glaucoma medication adherence and the associated factors among adults with glaucoma in Ethiopia.MethodsDatabase Searches to identify research articles was conducted on PubMed, EMBASE, Cochrane, AJOL, SCOPUS, and Google scholar without restriction on the date of publication. Data extraction was done using a data extraction Excel sheet. Analysis was performed using STATA version 16. Heterogeneity was assessed using I2statistics. Pooled prevalence and pooled odds ratio with a 95% confidence interval using a random effect model were computed.ResultWe included 6 studies with a total of 2101 participants for the meta-analysis. The magnitude of adherence to glaucoma medication was found to be 49.46% (95% CI [41.27-57.66]). Urban residence (OR=1.89, 95% CI; 1.29-2.49), normal visual acuity (OR=2.82, 95% CI; 0.85-4.80, P=0.01), and payment means for medication (OR=0.22, 95% CI; 0.09-0.34) were found to be statistically significant predictors of adherence.ConclusionThe magnitude of glaucoma medication adherence is lower than expected. Place of residence, visual acuity, and payment means had statistically significant associations with glaucoma medication adherence. Tailored health education on medication adherence and subsidization of glaucoma medication is recommended.