bluuebunny/crossref_metadata_2025_split huggingface dataset:
CoT: a transformer-based method for inferring tumor clonal copy number substructure from scDNA-seq data
Authors: Liu Furui , Shi Fangyuan , Du Fang , Cao Xiangmei , Yu Zhenhua 
Published: April 2024

Abstract
Single-cell DNA sequencing (scDNA-seq) has been an effective means to unscramble intra-tumor heterogeneity, while joint inference of tumor clones and their respective copy number profiles remains a challenging task due to the noisy nature of scDNA-seq data. We introduce a new bioinformatics method called CoT for deciphering clonal copy number substructure. The backbone of CoT is a Copy number Transformer autoencoder that leverages multi-head attention mechanism to explore correlations between different genomic regions, and thus capture global features to create latent embeddings for the cells. CoT makes it convenient to first infer cell subpopulations based on the learned embeddings, and then estimate single-cell copy numbers through joint analysis of read counts data for the cells belonging to the same cluster. This exploitation of clonal substructure information in copy number analysis helps to alleviate the effect of read counts non-uniformity, and yield robust estimations of the tumor copy numbers. Performance evaluation on synthetic and real datasets showcases that CoT outperforms the state of the arts, and is highly useful for deciphering clonal copy number substructure.
Bayesian joint modeling of multivariate longitudinal and survival outcomes using Gaussian copulas
Authors: Cho Seoyoon , Psioda Matthew A , Ibrahim Joseph G 
Published: April 2024

Abstract
There is an increasing interest in the use of joint models for the analysis of longitudinal and survival data. While random effects models have been extensively studied, these models can be hard to implement and the fixed effect regression parameters must be interpreted conditional on the random effects. Copulas provide a useful alternative framework for joint modeling. One advantage of using copulas is that practitioners can directly specify marginal models for the outcomes of interest. We develop a joint model using a Gaussian copula to characterize the association between multivariate longitudinal and survival outcomes. Rather than using an unstructured correlation matrix in the copula model to characterize dependence structure as is common, we propose a novel decomposition that allows practitioners to impose structure (e.g., auto-regressive) which provides efficiency gains in small to moderate sample sizes and reduces computational complexity. We develop a Markov chain Monte Carlo model fitting procedure for estimation. We illustrate the method’s value using a simulation study and present a real data analysis of longitudinal quality of life and disease-free survival data from an International Breast Cancer Study Group trial.
Reduced cardiac 123I-MIBG uptake is a robust biomarker of Lewy body disease in isolated rapid eye movement sleep behaviour disorder
Authors: Miyamoto Tomoyuki , Miyamoto Masayuki 
Published: April 2024

Abstract
Cardiac 123I-MIBG scintigraphy is used to assess the function of postganglionic presynaptic cardiac sympathetic nerve endings. 123I-MIBG cardiac uptake is markedly reduced in patients with isolated rapid eye movement sleep behaviour disorder, similar to Parkinson’s disease and dementia with Lewy bodies. As a result, it can be used as an early biomarker of isolated rapid eye movement sleep behaviour disorder. Most patients with isolated rapid eye movement sleep behaviour disorder develop synucleinopathies: Parkinson’s disease, dementia with Lewy bodies or multiple system atrophy. We aimed to investigate whether cardiac postganglionic denervation is present in patients with isolated rapid eye movement sleep behaviour disorder, as well as its possible usefulness as a marker for Lewy body disease status. This retrospective cohort study examined 306 patients (236 men and 70 women; mean age: 68.2 years; age range: 43–87 years) with polysomnography-confirmed isolated rapid eye movement sleep behaviour disorder who were followed for 1–3 months and underwent 123I-MIBG scintigraphy. We retrospectively analysed data from 306 patients with polysomnography-confirmed isolated rapid eye movement sleep behaviour disorder, and their longitudinal outcomes were documented at two centres. Among isolated rapid eye movement sleep behaviour disorder patients, reduced 123I-MIBG uptake was observed in the early and delayed images in 84.4 and 93.4% of patients, respectively, whereas 88.6% of the patients had a high washout rate. This large Japanese two-cohort study (n = 306) found that 91 patients (29.7%) developed an overt synucleinopathy (51 Parkinson’s disease, 35 dementia with Lewy bodies, 4 multiple system atrophy, and 1 cerebellar ataxia) during a mean follow-up duration of 4.72 ± 3.94 years, with a conversion risk of 14.5% at 3 years, 25.4% at 5 years, 41.4% at 8 years and 52.5% at 10 years. On the other hand, among patients with heart-to-mediastinum ratio &lt; 2.2 in the delayed images (n = 286), 85 (29.7%) developed Parkinson’s disease or dementia with Lewy bodies during a mean follow-up duration of 4.71 ± 3.94 years, with a conversion risk of 14.5% at 3 years, 25.6% at 5 years, 42.0% at 8 years and 51.0% at 10 years. Among the 33 patients who underwent repeat 123I-MIBG scintigraphy, there was a progressive decline in uptake over the next 4.2 years, with patients exhibiting reduced uptake progressing to Parkinson’s disease or dementia with Lewy bodies. In contrast, patients without decreased 123I-MIBG uptake progressed to multiple system atrophy. Reduced cardiac 123I-MIBG uptake was detected in over 90% of isolated rapid eye movement sleep behaviour disorder patients, with progression to Parkinson’s disease or dementia with Lewy bodies, rather than multiple system atrophy, over time. Reduced 123I-MIBG uptake is a robust maker for Lewy body disease among isolated rapid eye movement sleep behaviour disorder patients.
Magnetoencephalography-derived oscillatory microstate patterns across lifespan: the Cambridge centre for ageing and neuroscience cohort
Authors: Huang Yujing , Cao Chenglong , Dai Shenyi , Deng Hu , Su Li , Zheng Ju-Sheng 
Published: April 2024

Abstract
The aging brain represents the primary risk factor for many neurodegenerative disorders. Whole-brain oscillations may contribute novel early biomarkers of aging. Here, we investigated the dynamic oscillatory neural activities across lifespan (from 18 to 88 years) using resting Magnetoencephalography (MEG) in a large cohort of 624 individuals. Our aim was to examine the patterns of oscillation microstates during the aging process. By using a machine-learning algorithm, we identify four typical clusters of microstate patterns across different age groups and different frequency bands: left-to-right topographic MS1, right-to-left topographic MS2, anterior-posterior MS3 and fronto-central MS4. We observed a decreased alpha duration and an increased alpha occurrence for sensory-related microstate patterns (MS1 & MS2). Accordingly, theta and beta changes from MS1 & MS2 may be related to motor decline that increased with age. Furthermore, voluntary ‘top-down’ saliency/attention networks may be reflected by the increased MS3 & MS4 alpha occurrence and complementary beta activities. The findings of this study advance our knowledge of how the aging brain shows dysfunctions in neural state transitions. By leveraging the identified microstate patterns, this study provides new insights into predicting healthy aging and the potential neuropsychiatric cognitive decline.
The finance and growth nexus revisited: a truly Schumpeterian perspective
Authors: Bofinger Peter , Geißendörfer Lisa , Haas Thomas , Mayer Fabian 
Published: April 2024

Abstract
The nexus between the financial system and economic development is an issue that is as important for economic theory as it is for economic policy. This article provides a theoretical and empirical analysis of the standard literature that uses Joseph A. Schumpeter as an academic patron. The starting point of our study is the theoretical finding that Schumpeter is misinterpreted in the finance and growth literature. We show that this leads to puzzling empirical results and difficulties in explaining even fundamental relationships. After a critical analysis of the literature, we provide our own empirical analysis using a panel of 43 countries to explore the relationships between finance and growth variables based on a truly Schumpeterian and thus monetary growth model. Our empirical analysis shows that (i) dynamic credit variables are better at describing the finance and growth nexus than static credit variables, (ii) as saving is not a prerequisite for credit, we do not find a statistically significant relationship between household saving and gross domestic product (GDP) growth, and (iii) in line with the empirical literature, we find a bi-directional relationship between credit and GDP growth.
Pregnancy in patients with the Fontan operation
Authors: Montanaro Claudia , Boyle Siobhan , Wander Gurleen , Johnson Mark R , Roos-Hesselink Jolien W , Patel Roshni , Rafiq Isma , Silversides Candice K , Gatzoulis Michael A 
Published: April 2024

Abstract
Improved survival rates for patients with a Fontan circulation has allowed more women with this complex cardiac physiology to contemplate pregnancy. However, pregnancy in women with a Fontan circulation is associated with a high risk of adverse maternal and foetal outcomes, high rates of miscarriage, and preterm delivery. Factors associated with a successful pregnancy outcome are younger age, normal body weight, absence of significant functional limitation, no Fontan-related complications, and well-functioning single ventricle physiology. Appropriate care with timely preconception counselling and regular, frequent clinical reviews by a multidisciplinary team based at a tertiary centre improves the chance of a successful pregnancy. Empowerment of patients with education on their specific congenital cardiac condition and its projected trajectory helps them make informed choices regarding their health, reproductive choices, and assists them to achieve their life goals.
Effect of prolonged cooking at low temperatures on the eating quality of Tibetan pork: meat quality, water distribution, and microstructure
Authors: Liu Junmei , Li Xiefei , Jing Rong , Huang Xun , Geng Fang , Luo Zhang , Shang Peng , Liu Zhendong , Huang Qun 
Published: April 2024

Abstract

Objectives
Tibetan pork inhabit plateau regions and engage in extensive exercise. Their meat is firm and less palatable, but appropriate cooking conditions can improve the flavor of the meat. This study aimed to explore the impact of cooking temperature and time on the cooking loss rate, moisture content, tenderness, and color of Tibetan pork to elucidate their effects on the eating quality of this meat.

Materials and Methods
Physicochemical properties such as cooking losses and tenderness were evaluated, and protein structure was analyzed using Fourier-transform infrared and fluorescence spectroscopy.

Results
The results indicated a negative correlation between temperature and moisture content, which decreased from 72% to 65% as the temperature increased. Meanwhile, the oxidation of myofibrillar proteins substantially increased with cooking temperature and time, resulting in a gradual augmentation of the cooking loss and shear force of the pork. The migration of bound water and the release of free water from the pork were faster after treatment at 80 °C compared with 50 °C. The results of infrared spectroscopy suggested that prolonged cooking led to the conversion of the α-helix into the β-sheet in the secondary structure of myofibrillar proteins. The microstructures observed through scanning electron microscopy exhibited a gradual degradation of connective tissues in the muscles at high temperatures, and the fiber structure of the muscles became more condensed and granular, blurring the textural appearance of the muscles.

Conclusion
These results indicated that prolonged cooking time at a low temperature (steaming for 6 h at 50 °C) was conducive to the optimal tenderness of Tibetan pork. This study provides a theoretical basis for improving the meat quality of Tibetan pork products and developing more rational processing methods.
Advancements in pharmacological treatment of NAFLD/MASLD: a focus on metabolic and liver-targeted interventions
Authors: Ciardullo Stefano , Muraca Emanuele , Vergani Michela , Invernizzi Pietro , Perseghin Gianluca 
Published: April 2024

AbstractIn the present narrative review, we have summarized evidence on the pharmacological treatment of non-alcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD). We start by reviewing the epidemiology of the condition and its close association with obesity and type 2 diabetes. We then discuss how randomized–controlled trials are performed following guidance from regulatory agencies, including differences and similarities between requirements of the US Food and Drug Administration and the European Medicine Agency. Difficulties and hurdles related to limitations of liver biopsy, a large number of screening failures in recruiting patients, as well as unpredictable response rates in the placebo group are evaluated. Finally, we recapitulate the strategies employed for potential drug treatments of this orphan condition. The first is to repurpose drugs that originally targeted T2DM and/or obesity, such as pioglitazone, glucagon-like peptide 1 receptor agonists (liraglutide and semaglutide), multi-agonists (tirzepatide and retatrutide), and sodium-glucose transporter 2 inhibitors. The second is to develop drugs specifically targeting NAFLD/MASLD. Among those, we focused on resmetirom, fibroblast growth factor 21 analogs, and lanifibranor, as they are currently in Phase 3 of their clinical trial development. While many failures have characterized the field of pharmacological treatment of NAFLD/MASLD in the past, it is likely that approval of the first treatments is near. As occurs in many chronic conditions, combination therapy might lead to better outcomes. In the case of non-alcoholic steatohepatitis, we speculate that drugs treating underlying metabolic co-morbidities might play a bigger role in the earlier stages of disease, while liver-targeting molecules will become vital in patients with more advanced disease in terms of inflammation and fibrosis.
Examining the Social Networks Types and Their Effects on Caregiving Experience of Family Caregivers for Individuals With Dementia: A Mixed-Methods Study
Authors: Wang Jun , Liu Weichu , Li Xuelian , Ma Yingzhuo , Zhao Qinghua , Lü Yang , Xiao Mingzhao 
Published: April 2024

Abstract

Background and Objectives
Social networks are crucial to personal health, particularly among caregivers of individuals with dementia; however, different types of social networks among caregivers of those with dementia and how these differences are associated with caregiver burden and positive appraisal, remain underexamined. This study aims to depict dementia caregivers’ social network types, related factors, and impact on caregiving experiences.

Research Design and Methods
A questionnaire-based survey was conducted with a total of 237 family caregivers of individuals with dementia nested additional semistructured interviews conducted with 14 caregivers in Chongqing, China. A quantitative study was designed to collect data on personal and situational information, social networks, caregiver burden, and positive aspects of caregiving. Qualitative data were collected via semistructured interviews. Latent class analysis and multivariate regression analyses were applied to quantitative data, and inductive content analysis to qualitative data.

Results
The 3 social network types—family-limited (n = 39, 16.46%), family-dominant (n = 99, 41.77%), and diverse network (n = 99, 41.77%)—differed in age and sex of caregivers and individuals with dementia, stage of dementia, and caregiving intensity. Caregivers in family-dominant networks had a lower caregiver burden (β= −0.299, p = .003) and greater positive aspects of caregiving (β= 0.228, p = .021) than those in family-limited networks. Three themes—accessibility, reciprocity, and reliance—emerged as facilitators and barriers when asking for support. Caregivers frequently cited the perception of economic, practical, and emotional support, yet reported a lack of adequate formal support from healthcare providers.

Discussion and Implication
Family caregivers of individuals with dementia have different social network types that vary considerably among sociocultural contexts and perceive various types of support from social networks. Solid family networks and diverse social networks are contributors to long-term dementia care.
Evaluating the Efficacy of Time for Living and Caring: An Online Intervention to Support Dementia Caregivers’ Use of Respite
Authors: Iacob Eli , Caserta Michael , Donaldson Gary , Sparks Catharine , Terrill Alexandra , Thompson Amber , Wong Bob , Utz Rebecca L 
Published: April 2024

Abstract

Background and Objectives
Respite, defined as time away from caregiving, is the most requested type of caregiver support. Time for Living and Caring (TLC) is a virtual coaching “app” that helps caregivers schedule and plan their respite time-use. The objectives of this analysis are: (1) to assess the efficacy of the TLC intervention on respite time-use and on caregiver well-being and (2) to identify the key features of the intervention that serve as the likely mechanism of action.

Research Design and Methods
A sample of dementia caregivers (n = 163, 79% female, 84% White, 6% Hispanic, average age 62) were randomized into one of two intervention delivery methods. Intervention efficacy was evaluated using pre/post-comparisons of respite time-use and an additive “dosing” model that estimated unique parameters associated with the exposure to each specific intervention component.

Results
Both immediate and delayed-attention groups reported increased respite time. They also improved in their ability to plan and perceive benefit from their respite time-use over the 16-week intervention period. At 8 weeks, the immediate group did not change in anxiety, whereas the delayed group worsened (p &lt; .001). At 16 weeks, the groups were similar in their anxiety levels. By the 20-week follow-up period, when neither group had access to TLC, both experienced an increase in anxiety.

Discussion and Implications
TLC is a promising intervention that may support caregivers’ well-being, by helping them schedule and plan their respite to maximize its benefit. The provision of weekly coaching seems to be the intervention component (mechanism) associated with caregiver outcomes.

Clinical Trial Registration
NCT03689179
Barriers to smoking interventions in community healthcare settings: a scoping review
Authors: Coleman Cheryn , Ferguson Stuart G , Nash Rosie 
Published: April 2024

AbstractSmoking is one of the major causes of preventable death and is considered the greatest threat to global public health. While the prevalence of smoking has decreased, population growth has led to an increase in the absolute number of smokers. There are many proven smoking cessation interventions available to support smokers in their quit attempts. Most people who smoke, however, underutilize the treatments available to them. This scoping review aimed to identify the current barriers experienced by all stakeholders (smokers, service providers and policymakers) to existing evidence-based smoking cessation interventions in community healthcare settings. Five electronic databases (CINAHL, Ovid MEDLINE, PsycINFO, Scopus and Web of Science) were searched for relevant literature. A total of 40 eligible articles from different countries published between 2015 and 2022 were included in the review and content analysis carried out to identify the key barriers to smoking cessation interventions. Seven key themes were found to be common to all stakeholders: (i) literacy, (ii) competing demands and priorities, (iii) time, (iv) access to product, (v) access to service, (vi) workforce and (vii) motivation/readiness. These themes were mapped to the Capability, Opportunity, Motivation-Behaviour (COM-B) model. This study presents the effect the barriers within these themes have on current smoking cessation services and highlights priorities for future interventions.
Cytotoxic stress caused by azalamellarin D (AzaD) interferes with cellular protein translation by targeting the nutrient-sensing kinase mTOR
Authors: Meerod Tirawit , Sangsuwan Rapeepat , Klumthong Kanawut , Chantrathonkul Bunkuea , Phutubtim Nadgrita , Govitrapong Piyarat , Ruchirawat Somsak , Ploypradith Poonsakdi , Sopha Pattarawut 
Published: April 2024

Abstract
Analogs of pyrrole alkaloid lamellarins exhibit anticancer activity by modulating multiple cellular events. Lethal doses of several lamellarins were found to enhance autophagy flux in HeLa cells, suggesting that lamellarins may modulate protein homeostasis through the interference of proteins or kinases controlling energy and nutrient metabolism. To further delineate molecular mechanisms and their targets, our results herein show that azalamellarin D (AzaD) cytotoxicity could cause translational attenuation, as indicated by a change in eIF2α phosphorylation. Intriguingly, acute AzaD treatment promoted the phosphorylation of GCN2, a kinase that transduces the integrated stress response (ISR), and prolonged exposure to AzaD could increase the levels of the phosphorylated forms of eIF2α and the other ISR kinase protein kinase R (PKR). However, the effects of AzaD on ISR signalling were marginally abrogated in cells with genetic deletion of GCN2 and PKR, and evaluation of protein target engagement by cellular thermal shift assay (CETSA) revealed no significant interaction between AzaD and ISR kinases. Further investigation revealed that acute AzaD treatment negatively affected mechanistic target of rapamycin (mTOR) phosphorylation and signalling. The analyses by CETSA and computational modelling indicated that mTOR may be a possible protein target for AzaD. These findings indicate the potential for developing lamellarins as novel agents for cancer treatment.