bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of HLA-related genotype-guided prescribing in Singapore
Authors: Chua Hui Min , Limenta Michael , Ng Carol Yee Leng , Lo Elaine Ah gi 
Published: October 2024

Abstract

Purpose
To describe the implementation of human leukocyte antigen (HLA)–related genotype-guided prescribing in Singapore.

Summary
Various HLA alleles have been implicated in drug hypersensitivity syndromes (DHS). These include HLA-B*15:02, which has been associated with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis, HLA-B*58:01, which has been associated with increased risk of severe cutaneous adverse reactions with allopurinol use, and HLA-B*57:01, which has been associated with increased risk of hypersensitivity reactions with abacavir use. Integrating pharmacogenomics into patient care through genotype-guided prescribing potentially optimizes use of these drugs by reducing DHS-related and healthcare costs. We describe the prevalence of HLA-related DHS in Singapore, the cost-effectiveness of genotype-guided prescribing, and local policies and guidelines, as well as the impact of genotype-guided prescribing where available.

Conclusion
HLA-related genotype-guided prescribing has the potential to reduce the incidence of DHS and decrease healthcare costs, as seen in the success with carbamazepine. However, not all genotype-guided prescribing is cost-effective when implemented across the population, as was evident from local studies for allopurinol and abacavir. The cost-effectiveness of such measures may change over time with new data (eg, allele frequencies, test costs, drug prices, genotyping approach) and should be evaluated periodically and locally. Implementation of preemptive pharmacogenomics panel testing as part of routine clinical care may shift the threshold for cost-effectiveness and brings promise of further optimization of pharmacotherapy through precision medicine.
Predicting functional outcome in ischemic stroke patients using genetic, environmental, and clinical factors: a machine learning analysis of population-based prospective cohort study
Authors: Chen Siding , Xu Zhe , Yin Jinfeng , Gu Hongqiu , Shi Yanfeng , Guo Cang , Meng Xia , Li Hao , Huang Xinying , Jiang Yong , Wang Yongjun 
Published: October 2024

Abstract
Ischemic stroke (IS) is a leading cause of adult disability that can severely compromise the quality of life for patients. Accurately predicting the IS functional outcome is crucial for precise risk stratification and effective therapeutic interventions. We developed a predictive model integrating genetic, environmental, and clinical factors using data from 7819 IS patients in the Third China National Stroke Registry. Employing an 80:20 split, we randomly divided the dataset into development and internal validation cohorts. The discrimination and calibration performance of models were evaluated using the area under the receiver operating characteristic curves (AUC) for discrimination and Brier score with calibration curve in the internal validation cohort. We conducted genome-wide association studies (GWAS) in the development cohort, identifying rs11109607 (ANKS1B) as the most significant variant associated with IS functional outcome. We employed principal component analysis to reduce dimensionality on the top 100 significant variants identified by the GWAS, incorporating them as genetic factors in the predictive model. We employed a machine learning algorithm capable of identifying nonlinear relationships to establish predictive models for IS patient functional outcome. The optimal model was the XGBoost model, which outperformed the logistic regression model (AUC 0.818 versus 0.756, P &lt; .05) and significantly improved reclassification efficiency. Our study innovatively incorporated genetic, environmental, and clinical factors for predicting the IS functional outcome in East Asian populations, thereby offering novel insights into IS functional outcome.
MSlocPRED: deep transfer learning-based identification of multi-label mRNA subcellular localization
Authors: Zuo Yun , Zhang Bangyi , He Wenying , Bi Yue , Liu Xiangrong , Zeng Xiangxiang , Deng Zhaohong 
Published: October 2024

Abstract
Subcellular localization of messenger ribonucleic acid (mRNA) is a universal mechanism for precise and efficient control of the translation process. Although many computational methods have been constructed by researchers for predicting mRNA subcellular localization, very few of these computational methods have been designed to predict subcellular localization with multiple localization annotations, and their generalization performance could be improved.
In this study, the prediction model MSlocPRED was constructed to identify multi-label mRNA subcellular localization. First, the preprocessed Dataset 1 and Dataset 2 are transformed into the form of images. The proposed MDNDO–SMDU resampling technique is then used to balance the number of samples in each category in the training dataset. Finally, deep transfer learning was used to construct the predictive model MSlocPRED to identify subcellular localization for 16 classes (Dataset 1) and 18 classes (Dataset 2). The results of comparative tests of different resampling techniques show that the resampling technique proposed in this study is more effective in preprocessing for subcellular localization. The prediction results of the datasets constructed by intercepting different NC end (Both the 5' and 3' untranslated regions that flank the protein-coding sequence and influence mRNA function without encoding proteins themselves.) lengths show that for Dataset 1 and Dataset 2, the prediction performance is best when the NC end is intercepted by 35 nucleotides, respectively. The results of both independent testing and five-fold cross-validation comparisons with established prediction tools show that MSlocPRED is significantly better than established tools for identifying multi-label mRNA subcellular localization. Additionally, to understand how the MSlocPRED model works during the prediction process, SHapley Additive exPlanations was used to explain it. The predictive model and associated datasets are available on the following github: https://github.com/ZBYnb1/MSlocPRED/tree/main.
Deep coupled registration and segmentation of multimodal whole-brain images
Authors: Han Tingting , Wu Jun , Sheng Pengpeng , Li Yuanyuan , Tao ZaiYang , Qu Lei 
Published: October 2024

Abstract

Motivation
Recent brain mapping efforts are producing large-scale whole-brain images using different imaging modalities. Accurate alignment and delineation of anatomical structures in these images are essential for numerous studies. These requirements are typically modeled as two distinct tasks: registration and segmentation. However, prevailing methods, fail to fully explore and utilize the inherent correlation and complementarity between the two tasks. Furthermore, variations in brain anatomy, brightness, and texture pose another formidable challenge in designing multi-modal similarity metrics. A high-throughput approach capable of overcoming the bottleneck of multi-modal similarity metric design, while effective leveraging the highly correlated and complementary nature of two tasks is highly desirable.

Results
We introduce a deep learning framework for joint registration and segmentation of multi-modal brain images. Under this framework, registration and segmentation tasks are deeply coupled and collaborated at two hierarchical layers. In the inner layer, we establish a strong feature-level coupling between the two tasks by learning a unified common latent feature representation. In the outer layer, we introduce a mutually supervised dual-branch network to decouple latent features and facilitate task-level collaboration between registration and segmentation. Since the latent features we designed are also modality-independent, the bottleneck of designing multi-modal similarity metric is essentially addressed. Another merit offered by this framework is the interpretability of latent features, which allows intuitive manipulation of feature learning, thereby further enhancing network training efficiency and the performance of both tasks. Extensive experiments conducted on both multi-modal and mono-modal datasets of mouse and human brains demonstrate the superiority of our method.

Availability and implementation
The code is available at https://github.com/tingtingup/DCRS.
Auditory and vestibular function in mitochondrial patients harbouring the m.3243A&gt;G variant
Authors: Stefanetti Renae J , Newman Jane , Blain Alasdair P , Chisari Donella , Gorman Gráinne S , Rance Gary 
Published: October 2024

Abstract
Hearing impairment is a frequent clinical feature in patients with mitochondrial disease harbouring the pathogenic variant, m.3243A&gt;G. However, auditory neural dysfunction, its perceptual consequences and implications for patient management are not established. Similarly, the association with vestibular impairment has not yet been explored. This case–control study investigated in 12 adults with genetically confirmed m.3243A&gt;G adults [9 females; 45.5 ± 16.3 years (range 18–66); 47.1 ± 21.5 hearing level, dB] compared with 12 age, sex and hearing level-matched controls with sensory (cochlear level) hearing loss [9 females; 46.6 ± 11.8 years (range 23–59); 47.7 ± 25.4 hearing level, dB]. Participants underwent a battery of electroacoustic, electrophysiologic and perceptual tests, which included pure tone audiometry, otoacoustic emissions, auditory brainstem responses, auditory temporal processing measures, monaural/binaural speech perception, balance and vestibular testing and self-reported questionnaires (dizziness and hearing disability). Our findings showed evidence of auditory neural abnormality and perceptual deficits greater than expected for cochlear pathology. Compared with matched controls with sensory hearing loss, adults with mitochondrial disease harbouring m.3243A&gt;G had abnormal electrophysiologic responses from the VIII nerve and auditory brainstem (P = 0.005), an impaired capacity to encode rapidly occurring acoustic signal changes (P = 0.005), a reduced ability to localize sound sources (P = 0.028) and impaired speech perception in background noise (P = 0.008). Additionally, vestibular dysfunction (P = 0.011), greater perceived dizziness (P = 0.001) and reduced stance time (balance, P = 0.009) were also seen in participants with m.3243A&gt;G mitochondrial disease when compared with matched counterparts. This pilot study revealed that auditory evaluation including evoked potential responses from the auditory nerve/brainstem and speech perception in noise tests should form an important part of the management for individuals with m.3243A&gt;G-related mitochondrial disease. Those presenting with hearing impairment and symptoms concerning balance and dizziness should undergo vestibular testing and appropriate management.
Relevance of the basophil activation test in a cohort of 240 patients with chronic spontaneous urticaria
Authors: Pesqué David , Andrades Evelyn , Torres-Bosó Paloma , Soto Dulce , Gimeno Ramon , Pujol Ramon M , Yélamos José , Giménez-Arnau Ana M 
Published: October 2024

Abstract

Background
The basophil activation test (BAT) is considered to be the best biomarker to predict autoimmune chronic spontaneous urticaria (aiCSU). To date, few studies have investigated the utility of BAT in real-world clinical practice, the role of aiCSU biomarkers in relation to omalizumab therapy and the degree of association between different aiCSU tests.

Objectives
To analyse the clinical and laboratory features of a prospective cohort with chronic spontaneous urticaria (CSU) according to their BAT status, as well as to study omalizumab efficacy according to aiCSU biomarkers.

Methods
A prospective study was conducted from 2010 to 2024 in patients with CSU. BAT alongside other laboratory tests were performed, and clinical and therapeutic features were prospectively collected. Data obtained were compared according to BAT status (positive vs. negative). Furthermore, omalizumab drug survival was typified according to aiCSU biomarkers.

Results
In total, 240 patients were included in the study. Patients who were BAT positive presented more frequently with low IgE levels, higher occurrence of IgG antithyroid peroxidase (anti-TPO) positivity, autologous serum skin test (ASST) positivity, basopenia and eosinopenia. Multivariate logistic regression revealed that ASST [odds ratio (OR) 7.69, 95% confidence interval (CI) 2.81–21.0] and anti-TPO (OR 2.63, 95% CI 1.05–6.61) were associated with BAT positivity. All aiCSU biomarkers (BAT, ASST, combined ASST/BAT positivity and low IgE/anti-TPO+) were associated with significantly shorter omalizumab survival because of treatment failure. In the cohort, both low IgE/anti-TPO+ and ASST were associated with BAT positivity.

Conclusions
The use of BAT in clinical practice delineates a subgroup of patients with specific clinical, laboratory and therapeutic features, including increased omalizumab failure.
Triggerable peroxidase-tagged primer enables naked eye monitoring of PCR amplification
Authors: Munakata Hironao , Sohma Yuri , Ishida Kotaro , Morita Eiji , Sato Shin-ichi , Hagihara Masaki 
Published: October 2024

Abstract
The guanine quadruplex structure, formed within guanine-rich sequences, demonstrates peroxidase-like activity when bound to a hemin-like small molecule. This property has been used for nucleic acid detection. We present a method using a guanine quadruplex-based triggerable peroxidase-tagged primer, where an unpaired adenine base in synthesized strands activates the peroxidase activity of the guanine quadruplex–hemin complex. This approach enables sensitive, visual detection of target DNA through naked-eye observation, eliminating the need for PCR product purification.
A test method for assessing chronic oral toxicity of a pesticide to solitary nesting orchard bees, Osmia spp. (Hymenoptera: Megachilidae)
Authors: Cabrera Ana R , Zuber Joshua , Hamaekers Niklas , Olmstead Allen , Jensen Pamela , Karunanithi Prema , Schmehl Daniel R , Exeler Nina 
Published: October 2024

Abstract
Orchard bees of the genus Osmia Panzer are important pollinators of fruit trees in various regions of the world, with some species commercially available in the United States and Europe. In addition to their pollination services, Osmia lignaria, Osmia cornifrons, Osmia bicornis, and Osmia cornuta have been identified as potential model species for solitary bees in pesticide risk assessment and have been used for the development of new methods to test acute lethal effects via contact and oral routes of exposure. Our goal was to expand the available methodology to characterize the toxicity of pesticides for these solitary bees through a chronic oral test for adult bees. Chronic oral toxicity of pesticides to orchard bees has been reported, but methods differ among research groups. In our study, O. lignaria, O. cornifrons, O. bicornis, and O. cornuta female bees had access to sucrose solution ad libitum in separate, species-specific 10-day tests. Mean body mass, mean daily consumption, and survival differed among the studied bee species. The dose–response test design was validated with dimethoate, a reference toxic compound, and chronic toxicity endpoints were estimated for the 4 Osmia species. The median lethal daily doses normalized by weight for O. lignaria, O. bicornis, O. cornuta, and O. cornifrons were within the same order of magnitude at 0.23, 0.26, 0.49, and 0.61 µg dimethoate/g bee/day, respectively. The methodology described here was aligned as much as possible with the available honey bee and bumble bee standard methods to facilitate the comparison of chronic toxicity profiles among bee species.
Sex differences in the relationship between body composition and cardiac structure and function
Authors: Hartman Heidi S , Kim Eunyoung , Carbone Salvatore , Miles Caleb H , Reilly Muredach P 
Published: October 2024

Abstract

Aims
The purpose of this study was to characterize sex differences in the relationship between body composition and cardiac structure and function. In secondary analyses, we explored pathophysiologic mediators of these relationships.

Methods and results
In a cross-sectional analysis of 25 063 UK Biobank participants (54% female, median age 55 years), the sex-specific associations of visceral adipose tissue volume (VAT), appendicular lean mass (ALM), and muscle fat infiltration (MFI) with cardiac magnetic resonance (CMR) measures of cardiac structure and function were assessed using linear regression models. Using causal mediation analysis, 10 biomarkers were explored as mediators of the relationship between adipose depots and cardiac parameters. VAT was associated with increased left ventricular mass (LVM; βwomen = 0.54, βmen = 0.00, Pint = 0.01) and wall thickness (βwomen = 0.12, βmen = 0.08, Pint &lt; 0.001) in women only. A similar sex-specific pattern was observed for MFI effects on LVM (βwomen = 0.44, βmen = 0.03, Pint &lt; 0.001). ALM was associated with increased LVM and LV volumes in both women and men. In mediation analyses, insulin resistance as measured by triglycerides/high-density lipoprotein ratio was a potential partial mediator of VAT effects on chamber dimensions.

Conclusion
In the largest and most rigorous analyses of body composition and cardiac parameters to date, we demonstrated that VAT is associated with increased LVM and wall thickness in women but not in men. MFI association with cardiac parameters was similar to VAT, significant in women but not in men.
The association between non-alcoholic liver fatty disease and coronary artery calcification: a two-sample Mendelian randomization study
Authors: He Liaoming , Tiemuerniyazi Xieraili , Yang Ziang , Huang Shengkang , Chen Lianxin , Nan Yifeng , Song Yangwu , Feng Wei 
Published: October 2024

Abstract

Aims
Although prior observational studies have suggested that patients with non-alcoholic fatty liver disease (NAFLD) may have a higher risk of coronary artery calcification (CAC), these findings remain controversial. This study aimed to explore the causal association between NAFLD and CAC at genetic level by two-sample Mendelian randomization (MR) analysis.

Methods and results
Utilizing summary-level data from multiple large-scale genome-wide association studies in European populations, a two-sample MR analysis was initially conducted to explore the potential causal association between NAFLD and CAC. The results of the MR analysis were pooled through random-effect meta-analysis. The inverse variance weighting method served as the primary approach for MR analysis. Additionally, the weighted median, MR-Egger, and MR-pleiotropy residual sum and outlier methods were applied for sensitivity analysis. Summary-level data on liver fatty content was utilized for validation analysis, while summary-level data on cirrhosis served as positive control, further ensuring the validity and robustness of our findings. Reverse MR analysis was performed to assess the association between CAC and NAFLD, employing instrument variables derived from CAC. The MR analysis indicated that genetically predicted NAFLD had no effects on the risk of CAC [Beta: 0.01, 95% confidence interval (CI): −0.02 to 0.03, P = 0.74]. Likewise, the reverse MR analysis found no significant genetic association between CAC and NAFLD (odds ratio: 1.00, 95% CI: 0.96–1.06, P = 0.88). Validation analysis yielded consistent results, showing no significant association between fatty liver content and CAC.

Conclusion
Our two-sample MR analysis did not support that there is a causal association between NAFLD and CAC at genetic level. The association between NAFLD and CAC reported in some previous observational studies may rely on NAFLD complicated with metabolic disorders, rather than being directly linked to the hepatic steatosis.
The epistatic relationship of Drosophila melanogaster CtIP and Rif1 in homology-directed repair of DNA double-strand breaks
Authors: Thomas Makenzie S , Pillai Gautham S , Butler Margaret A , Fernandez Joel , LaRocque Jeannine R 
Published: October 2024

Abstract
Double-strand breaks (DSBs) are genotoxic DNA lesions that pose significant threats to genomic stability, necessitating precise and efficient repair mechanisms to prevent cell death or mutations. DSBs are repaired through nonhomologous end-joining (NHEJ) or homology-directed repair (HDR), which includes homologous recombination (HR) and single-strand annealing (SSA). CtIP and Rif1 are conserved proteins implicated in DSB repair pathway choice, possibly through redundant roles in promoting DNA end-resection required for HDR. Although the roles of these proteins have been well-established in other organisms, the role of Rif1 and its potential redundancies with CtIP in Drosophila melanogaster remain elusive. To examine the roles of DmCtIP and DmRif1 in DSB repair, this study employed the direct repeat of white (DR-white) assay, tracking across indels by decomposition (TIDE) analysis, and P{wIw_2 kb 3′} assay to track repair outcomes in HR, NHEJ, and SSA, respectively. These experiments were performed in DmCtIPΔ/Δ single mutants, DmRif1Δ/Δ single mutants, and DmRif1Δ/Δ; DmCtIPΔ/Δ double mutants. This work demonstrates significant defects in both HR and SSA repair in DmCtIPΔ/Δ and DmRif1Δ/Δ single mutants. However, experiments in DmRif1Δ/Δ; DmCtIPΔ/Δ double mutants reveal that DmCtIP is epistatic to DmRif1 in promoting HDR. Overall, this study concludes that DmRif1 and DmCtIP do not perform their activities in a redundant pathway, but rather DmCtIP is the main driver in promoting HR and SSA, most likely through its role in end resection.
Caregiving Trajectories and Unmet Care Needs in Later Life
Authors: Freedman Vicki A , Cornman Jennifer C , Wolff Jennifer L 
Published: October 2024

Abstract

BACKGROUND AND OBJECTIVES
The evolution of care networks accompanying older adults’ changing care needs–and implications for unmet care needs–are not well described.

RESEARCH DESIGN AND METHODS
Using group-based trajectory models, we identify 4 incident care need patterns (“care need trajectory groups”) for 1,038 older adults in the 2012-2018 National Health and Aging Trends Study and 5 caregiving patterns (“caregiving trajectory groups”) and a transient group among their 4,106 caregivers. We model associations between care need/caregiving trajectory groups and the rate of (approximating the proportion of rounds with) unmet care needs. We illustrate how predicted rates vary by care need trajectory groups and by network composition for networks with 2 caregivers.

RESULTS
The percentage of rounds with unmet care needs varies from 13% among older adults with few, stable needs to 62% among those with many, stable needs (p&lt;.01). In models, care need trajectory group is strongly associated with the rate of unmet care needs; among those with steep increasing care needs, network composition is also predictive. For older adults with steep increasing care needs, when one caregiver provides high, variable and another medium, stable care hours, the predicted rate of unmet care needs is low (0.16) and similar to those with few, stable care needs (0.12).

DISCUSSION AND IMPLICATIONS
Findings highlight the complexity and heterogeneity of older adults’ care needs and caregiving patterns over time. For those with rapidly increasing needs, identifying and assessing the evolving care network may be a fruitful direction for forestalling unmet care needs.