bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leveraging new methods for comprehensive characterization of mitochondrial DNA in esophageal squamous cell carcinoma
Authors: Zhuang Xuehan , Ye Rui , Zhou Yong , Cheng Matthew Yibo , Cui Heyang , Wang Longlong , Zhang Shuangping , Wang Shubin , Cui Yongping , Zhang Weimin 
Published: April 2024

Abstract
Background
Mitochondria play essential roles in tumorigenesis; however, little is known about the contribution of mitochondrial DNA (mtDNA) to esophageal squamous cell carcinoma (ESCC). Whole-genome sequencing (WGS) is by far the most efficient technology to fully characterize the molecular features of mtDNA; however, due to the high redundancy and heterogeneity of mtDNA in regular WGS data, methods for mtDNA analysis are far from satisfactory.

Methods
Here, we developed a likelihood-based method dMTLV to identify low-heteroplasmic mtDNA variants. In addition, we described fNUMT, which can simultaneously detect non-reference nuclear sequences of mitochondrial origin (non-ref NUMTs) and their derived artifacts. Using these new methods, we explored the contribution of mtDNA to ESCC utilizing the multi-omics data of 663 paired tumor-normal samples.

Results
dMTLV outperformed the existing methods in sensitivity without sacrificing specificity. The verification using Nanopore long-read sequencing data showed that fNUMT has superior specificity and more accurate breakpoint identification than the current methods.
Leveraging the new method, we identified a significant association between the ESCC overall survival and the ratio of mtDNA copy number of paired tumor-normal samples, which could be potentially explained by the differential expression of genes enriched in pathways related to metabolism, DNA damage repair, and cell cycle checkpoint. Additionally, we observed that the expression of CBWD1 was downregulated by the non-ref NUMTs inserted into its intron region, which might provide precursor conditions for the tumor cells to adapt to a hypoxic environment. Moreover, we identified a strong positive relationship between the number of mtDNA truncating mutations and the contribution of signatures linked to tumorigenesis and treatment response.

Conclusions
Our new frameworks promote the characterization of mtDNA features, which enables the elucidation of the landscapes and roles of mtDNA in ESCC essential for extending the current understanding of ESCC etiology. dMTLV and fNUMT are freely available from https://github.com/sunnyzxh/dMTLV and https://github.com/sunnyzxh/fNUMT, respectively.
Race-specific coregulatory and transcriptomic profiles associated with DNA methylation and androgen receptor in prostate cancer
Authors: Ramakrishnan Swathi , Cortes-Gomez Eduardo , Athans Sarah R. , Attwood Kristopher M. , Rosario Spencer R. , Kim Se Jin , Mager Donald E. , Isenhart Emily G. , Hu Qiang , Wang Jianmin , Woloszynska Anna 
Published: April 2024

AbstractBackgroundProstate cancer is a significant health concern, particularly among African American (AA) men who exhibit higher incidence and mortality compared to European American (EA) men. Understanding the molecular mechanisms underlying these disparities is imperative for enhancing clinical management and achieving better outcomes.MethodsEmploying a multi-omics approach, we analyzed prostate cancer in both AA and EA men. Using Illumina methylation arrays and RNA sequencing, we investigated DNA methylation and gene expression in tumor and non-tumor prostate tissues. Additionally, Boolean analysis was utilized to unravel complex networks contributing to racial disparities in prostate cancer.ResultsWhen comparing tumor and adjacent non-tumor prostate tissues, we found that DNA hypermethylated regions are enriched for PRC2/H3K27me3 pathways and EZH2/SUZ12 cofactors. Olfactory/ribosomal pathways and distinct cofactors, including CTCF and KMT2A, were enriched in DNA hypomethylated regions in prostate tumors from AA men. We identified race-specific inverse associations of DNA methylation with expression of several androgen receptor (AR) associated genes, including theGATAfamily of transcription factors andTRIM63. This suggests that race-specific dysregulation of the AR signaling pathway exists in prostate cancer. To investigate the effect of AR inhibition on race-specific gene expression changes, we generated in-silico patient-specific prostate cancer Boolean networks. Our simulations revealed prolonged AR inhibition causes significant dysregulation of TGF-β, IDH1, and cell cycle pathways specifically in AA prostate cancer. We further quantified global gene expression changes, which revealed differential expression of genes related to microtubules, immune function, and TMPRSS2-fusion pathways, specifically in prostate tumors of AA men. Enrichment of these pathways significantly correlated with an altered risk of disease progression in a race-specific manner.ConclusionsOur study reveals unique signaling networks underlying prostate cancer biology in AA and EA men, offering potential insights for clinical management strategies tailored to specific racial groups. Targeting AR and associated pathways could be particularly beneficial in addressing the disparities observed in prostate cancer outcomes in the context of AA and EA men. Further investigation into these identified pathways may lead to the development of personalized therapeutic approaches to improve outcomes for prostate cancer patients across different racial backgrounds.
A comparison of various insulin resistance indices and the possibility of hypertension in military adults: CHIEF study
Authors: Huang Wei-Che , Tsai Kun-Zhe , Yang Kai-Ti , Chen Han-Hsing , Kwon Younghoon , Lin Gen-Min 
Published: April 2024

Abstract
Background
Insulin resistance is associated with the development of hypertension, whereas there were rare studies comparing various non-insulin based insulin resistance (NI-IR) indices for the possibility of hypertension among young and middle-aged adults.

Methods
This cross-sectional study included a total of 4,080 military personnel, aged 18–50 years, without antihypertensive medications therapy in 2014. All subjects received annual health examinations for blood pressure (BP) measurements. Stage I isolated diastolic hypertension (IDH) and isolated systolic hypertension (ISH) and combined hypertension were respectively defined as systolic BP (SBP) < 130 mmHg/diastolic BP (DBP) 80–89 mmHg, SBP 130–139 mmHg/DBP < 80 mmHg, and SBP 130–139 mmHg/DBP 80–89 mmHg. The cut-off values of stage II hypertension for SBP and DBP were 140–159 mmHg and 90–99 mmHg, respectively. Four NI-IR indices included the serum triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio, TyG index, Metabolic Score for IR (METS-IR) and ZJU index which were defined according to their specific formula. Multiple logistic regression analysis with adjustments for age, sex, anthropometrics, substance use, kidney function, serum uric acid, atherogenic cholesterols and physical activity was performed to determine the associations.

Results
There were 1,024 subjects with hypertension (25.1%) in which 739 were stage I hypertension, and 285 were stage II hypertension. For total hypertension, there were an association with TyG and METS-IR indices [odds ratios (ORs) and 95% confidence intervals: 1.432 (1.215–1.688) and 1.553 (1.040–2.321), respectively]. For hypertension subtypes, TyG index was positively associated with overall, stage I, and stage II ISH [ORs: 1.447 (1.149–1.823), 1.317 (1.029–1.687), and 2.011 (1.351–2.994), respectively], while TG/HDL-C, METS-IR and ZJU indices were merely associated with stage II ISH [ORs: 1.053 (1.006–1.103), 3.001 (1.171–7.696) and 1.009 (1.000-1.017), respectively]. In addition, TyG and METS-IR indices were positively associated with stage II IDH [ORs: 1.813 (1.207–2.721) and 2.85 (1.080–7.520), respectively], and TyG index was also associated with combined hypertension [OR: 1.425 (1.007–1.833)].

Conclusion
Among young and middle-aged adults, insulin resistance assessed by the four NI-IR indices was positively associated with stage II ISH, while only TyG index had a significant association for both stage II IDH and combined hypertension.
Brain 18 F-FDG PET reveals cortico-subcortical hypermetabolic dysfunction in juvenile neuropsychiatric systemic lupus erythematosus
Authors: Rodrigo Sebastian , Costi Stefania , Ellul Pierre , Aubart Melodie , Boddaert Nathalie , Auvin Stephane , Elmaleh Monique , Ntorkou Alexandra , Bader-Meunier Brigitte , Lebon Vincent , Melki Isabelle , Chiron Catherine 
Published: April 2024

Abstract
Background
In juvenile systemic lupus erythematosus (j-SLE) with neuropsychiatric (NP) symptoms, there is a lack of diagnostic biomarkers. Thus, we study whether PET-FDG may identify any metabolic dysfunction in j-NPSLE.

Methods
A total of 19 18FDG-PET exams were consecutively performed using PET-MRI system in 11 non-sedated patients presenting with j-NPSLE (11-18y) for less than 18 months (m) and without any significant lesion at MRI. Psychiatric symptoms were scored from 0 (none) to 3 (severe) at PET time. PET images were visually analyzed and voxel-based analyses of cerebral glucose metabolism were performed using statistical parametric mapping (spm) with an age-matched control group, at threshold set > 50 voxels using both p < 0.001 uncorrected (unc.) and p < 0.05 corrected family wise error (FWE).

Results
Patients exhibited mainly psychiatric symptoms, with diffuse inflammatory j-NPSLE. First PET (n = 11) was performed at a mean of 15y of age, second/third PET (n = 7/n = 1) 6 to 19 m later. PET individual analysis detected focal bilateral anomalies in 13/19 exams visually but 19/19 using spm (unc.), mostly hypermetabolic areas (18/19). A total of 15% of hypermetabolic areas identified by spm had been missed visually. PET group analysis (n = 19) did not identify any hypometabolic area, but a large bilateral cortico-subcortical hypermetabolic pattern including, by statistical decreasing order (unc.), thalamus, subthalamic brainstem, cerebellum (vermis and cortex), basal ganglia, visual, temporal and frontal cortices. Mostly the subcortical hypermetabolism survived to FWE analysis, being most intense and extensive (51% of total volume) in thalamus and subthalamus brainstem. Hypermetabolism was strictly subcortical in the most severe NP subgroup (n = 8, scores 2–3) whereas it also extended to cerebral cortex, mostly visual, in the less severe subgroup (n = 11, scores 0–1), but difference was not significant. Longitudinal visual analysis was inconclusive due to clinical heterogeneity.

Conclusions
j-NPSLE patients showed a robust bilateral cortico-subcortical hypermetabolic network, focused subcortically, particularly in thalamus, proportionally to psychiatric features severity. Further studies with larger, but homogeneous, cohorts are needed to determine the sensitivity and specificity of this dysfunctional pattern as a potential biomarker in diffuse inflammatory j-NPSLE with normal brain MRI.
Arab male physicians’ perceptions about their own smoking behaviors: a qualitative study
Authors: Obeid Samira , Idilbi Nasra , Agbarya Abed , Admi Hanna 
Published: April 2024

Abstract
Background
Smoking remains the leading preventable cause of disease, disability, and death worldwide. Although physicians have high levels of health literacy with awareness of the consequences of smoking and their essential role in smoking cessation of patients, some physicians continue to smoke. Rates of smoking among Arab male physicians are high. This study aimed to gain insights into Arab male physician’s perceptions of their own smoking behaviors and their professional role in health promotion.

Methods
Using purposive sampling, we recruited 25 Arab male physicians working in hospital and community clinic settings who currently smoke. Semi-structured, hour-long, interviews were held during January—June 2022. We then performed a thematic analysis of the interview data.

Results
The analysis revealed three categories, two sub-categories, and 15 emerging themes. The category ‘Antecedents: prior to becoming a physician’ revealed the themes: smoking experience during adolescence; social and ethnic culture; stress during medical studies; and on & off periods of quitting smoking. The category ‘Physicians’ perception of smoking’ was sorted into two sub-categories: (1) Personal aspects, including the themes ‘relaxation from stress’, ‘self-compensation’, ‘addiction’, and ‘enjoyable experience’, and (2) Professional aspects, including the themes ‘lack of knowledge about cessation’, ‘inadequate workplace support’, ‘motivation to consult patients’, and ‘awareness of their role as primary care physicians’. The category’Impacts’ revealed the themes ‘personal health and well-being’, ‘professional competence’, and ‘professional image in public’.

Conclusions
This study provides an in-depth understanding of the personal, socio-cultural, and professional aspects of the phenomenon of Arab male smoking physicians from their perspective. Based on this information, we recommend developing programs that support and empower all physicians to cope better with their personal and professional stress as well as instituting programs that will provide all physicians with specific knowledge and skills related to smoking cessation. These programs should improve the ability of physicians to serve as positive role models for their patients for preventing and ceasing smoking, thus enhancing the image of the medical profession and, most importantly, improving the health of the public.
The discrete analogue of high-order differential operator and its application to finding coefficients of optimal quadrature formulas
Authors: Shadimetov K. M. , Davronov J. R. 
Published: April 2024

AbstractThe discrete analog of the differential operator plays a significant role in constructing interpolation, quadrature, and cubature formulas. In this work, we consider a discrete analog $D_{m}(h\beta )$

D
m

(
h
β
)
of the differential operator $\frac{d^{2m}}{dx^{2m}}+1$

d

2
m

d

x

2
m

+
1
designed specifically for even natural numbers m. The operator’s effectiveness in constructing an optimal quadrature formula in the $L_{2}^{(2,0)}(0,1)$

L
2

(
2
,
0
)

(
0
,
1
)
space is demonstrated. The errors of the optimal quadrature formula in the $W_{2}^{(2,1)}(0,1)$

W
2

(
2
,
1
)

(
0
,
1
)
space and in the $L_{2}^{(2,0)}(0,1)$

L
2

(
2
,
0
)

(
0
,
1
)
space are compared numerically. The numerical results indicate that the optimal quadrature formula constructed in this work has a smaller error than the one constructed in the $W_{2}^{(2,1)}(0,1)$

W
2

(
2
,
1
)

(
0
,
1
)
space.
Cost of start-up activities to implement a community-level opioid overdose reduction intervention in the HEALing Communities Study
Authors: Montoya Iván D. , Watson Colleen , Aldridge Arnie , Ryan Danielle , Murphy Sean M. , Amuchi Brenda , McCollister Kathryn E. , Schackman Bruce R. , Bush Joshua L. , Speer Drew , Harlow Kristin , Orme Stephen , Zarkin Gary A. , Castry Mathieu , Seiber Eric E. , Barocas Joshua A. , Linas Benjamin P. , Starbird Laura E. 
Published: April 2024

Abstract
Background
Communities That HEAL (CTH) is a novel, data-driven community-engaged intervention designed to reduce opioid overdose deaths by increasing community engagement, adoption of an integrated set of evidence-based practices, and delivering a communications campaign across healthcare, behavioral-health, criminal-legal, and other community-based settings. The implementation of such a complex initiative requires up-front investments of time and other expenditures (i.e., start-up costs). Despite the importance of these start-up costs in investment decisions to stakeholders, they are typically excluded from cost-effectiveness analyses. The objective of this study is to report a detailed analysis of CTH start-up costs pre-intervention implementation and to describe the relevance of these data for stakeholders to determine implementation feasibility.

Methods
This study is guided by the community perspective, reflecting the investments that a real-world community would need to incur to implement the CTH intervention. We adopted an activity-based costing approach, in which resources related to hiring, training, purchasing, and community dashboard creation were identified through macro- and micro-costing techniques from 34 communities with high rates of fatal opioid overdoses, across four states—Kentucky, Massachusetts, New York, and Ohio. Resources were identified and assigned a unit cost using administrative and semi-structured-interview data. All cost estimates were reported in 2019 dollars.

Results
State-level average and median start-up cost (representing 8–10 communities per state) were $268,657 and $175,683, respectively. Hiring and training represented 40%, equipment and infrastructure costs represented 24%, and dashboard creation represented 36% of the total average start-up cost. Comparatively, hiring and training represented 49%, purchasing costs represented 18%, and dashboard creation represented 34% of the total median start-up cost.

Conclusion
We identified three distinct CTH hiring models that affected start-up costs: hospital-academic (Massachusetts), university-academic (Kentucky and Ohio), and community-leveraged (New York). Hiring, training, and purchasing start-up costs were lowest in New York due to existing local infrastructure. Community-based implementation similar to the New York model may have lower start-up costs due to leveraging of existing infrastructure, relationships, and support from local health departments.
Triglyceride-glucose-waist circumference index predicts the incidence of cardiovascular disease in Korean populations: competing risk analysis of an 18-year prospective study
Authors: Ahn Sung Ho , Lee Hye Sun , Lee Jun-Hyuk 
Published: April 2024

Abstract
Background
The triglyceride and glucose-waist circumference (TyG-WC) index demonstrated a strong association with insulin resistance, especially in Asian population. However, evidence on the association between TyG-WC index and the occurrence of cardiovascular disease (CVD) is limited. This study aimed to verify association between the TyG-WC index and the occurrence of CVD by considering all-cause mortality as a competing risk.

Methods
The study included 7482 participants divided into four groups based on the TyG-WC index quartiles. Kaplan–Meier curves illustrated cumulative incidence rates of CVD and all-cause mortality during the follow-up period. Log-rank tests determined group differences. The Cox proportional hazard spline curve demonstrates the dose-dependent relationship between the TyG-WC index and incident CVD. Modified Cox regression (Fine and Gray) estimated hazard ratios (HRs) with 95% CIs for incident CVD, treating death as a competing risk. Death event after incident CVD was excluded from the death count.

Results
During the median 15.94 year of follow-up period, a total of 691 (9.24%) new-onset CVD cases and 562 (7.51%) all-cause mortality cases were confirmed. Cox proportional hazard spline curves suggested that TyG-WC index exhibited a dose-dependent positive correlation with incident CVD. The cumulative incidence rate of CVD was significantly higher in the groups with higher TyG-WC index quartiles in Kaplan–Meier curves. The adjusted HR (95% CI) for incident CVD in Q2–Q4, compared with Q1, was 1.47 (1.12–1.93), 1.91 (1.44–2.54) and 2.24 (1.63–3.07), respectively. There was no significant association between TyG-WC index and all-cause mortality. Specifically, angina and stroke were significantly associated with the TyG-WC index, in contrast to myocardial infarction and peripheral artery disease.

Conclusions
The TyG-WC index was positively associated with incident CVD even considering all-cause mortality as a competing risk. Therefore, TyG-WC index may be a valuable marker for predicting the occurrence of CVD.
Dietary fasting and time-restricted eating in Huntington’s disease: therapeutic potential and underlying mechanisms
Authors: Wells Russell G. , Neilson Lee E. , McHill Andrew W. , Hiller Amie L. 
Published: April 2024

AbstractHuntington's disease (HD) is a devastating neurodegenerative disorder caused by aggregation of the mutant huntingtin (mHTT) protein, resulting from a CAG repeat expansion in the huntingtin gene HTT. HD is characterized by a variety of debilitating symptoms including involuntary movements, cognitive impairment, and psychiatric disturbances. Despite considerable efforts, effective disease-modifying treatments for HD remain elusive, necessitating exploration of novel therapeutic approaches, including lifestyle modifications that could delay symptom onset and disease progression. Recent studies suggest that time-restricted eating (TRE), a form of intermittent fasting involving daily caloric intake within a limited time window, may hold promise in the treatment of neurodegenerative diseases, including HD. TRE has been shown to improve mitochondrial function, upregulate autophagy, reduce oxidative stress, regulate the sleep–wake cycle, and enhance cognitive function. In this review, we explore the potential therapeutic role of TRE in HD, focusing on its underlying physiological mechanisms. We discuss how TRE might enhance the clearance of mHTT, recover striatal brain-derived neurotrophic factor levels, improve mitochondrial function and stress-response pathways, and synchronize circadian rhythm activity. Understanding these mechanisms is critical for the development of targeted lifestyle interventions to mitigate HD pathology and improve patient outcomes. While the potential benefits of TRE in HD animal models are encouraging, future comprehensive clinical trials will be necessary to evaluate its safety, feasibility, and efficacy in persons with HD.
Detecting oracle bone inscriptions via pseudo-category labels
Authors: Fu Xinran , Zhou Rixin , Yang Xi , Li Chuntao 
Published: April 2024

Abstract
Oracle bone inscriptions (OBIs) are the earliest Chinese characters and reserve abundant historical information. OBIs are detected by locating their positions in digital images. This has been a foundational task in modern archeological studies. Due to the development of deep neural networks(DNNs) in computer vision, detecting OBIs can be implemented by a more concise method instead of designing complicated hand-crafted features. However, existing models cannot perform well when noise areas are similar to some inscriptions. In this work, we present a simple but effective pseudo-label-based architecture for OBIs detection. Different from previous approaches, our method performs OBIs detection with the employment of information from multilabel annotations rather than single location information. We append a plug-and-play module that predicts the pseudo-label of an inscription after the backbone network for learning the particular structure prior to each inscription and brings this information to the backbone network by means of feature fusion. We make remarkable improvements on different backbone networks when using the proposed method on an OBIs detection dataset. The quantitative and qualitative results show that the proposed model can detect OBIs well and is an effective tool for assisting in the discovery and recognition of ancient writing.