bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of differentially methylated regions associated with both liver fibrosis and hepatocellular carcinoma
Authors: Kurokawa Suguru , Kobori Takuro , Yoneda Masato , Ogawa Yuji , Honda Yasushi , Kessoku Takaomi , Imajo Kento , Saito Satoru , Nakajima Atsushi , Hotta Kikuko 
Published: February 2024

Abstract
Background
Liver fibrosis is a major risk factor for hepatocellular carcinoma (HCC). We have previously reported that differentially methylated regions (DMRs) are correlated with the fibrosis stages of metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, the methylation levels of those DMRs in liver fibrosis and subsequent HCC were examined.

Methods
The methylation levels of DMRs were investigated using alcoholic cirrhosis and HCC (GSE60753). The data of hepatitis C virus-infected cirrhosis and HCC (GSE60753), and two datasets (GSE56588 and GSE89852) were used for replication analyses. The transcriptional analyses were performed using GSE114564, GSE94660, and GSE142530.

Results
Hypomethylated DMR and increased transcriptional level of zinc finger and BTB domain containing 38 (ZBTB38) were observed in HCC. Hypermethylated DMRs, and increased transcriptional levels of forkhead box K1 (FOXK1) and zinc finger CCCH-type containing 3 (ZC3H3) were observed in HCC. The methylation levels of DMR of kazrin, periplakin interacting protein (KAZN) and its expression levels were gradually decreased as cirrhosis progressed to HCC.

Conclusions
Changes in the methylation and transcriptional levels of ZBTB38, ZC3H3, FOXK1, and KAZN are important for the development of fibrosis and HCC; and are therefore potential therapeutic targets and diagnostic tools for cirrhosis and HCC.
Combined effects of vitamin D deficiency and systemic inflammation on all-cause mortality and cause-specific mortality in older adults
Authors: Zhang Chi , Cui Ju , Li Shaojie , Shen Ji , Luo Xuanmei , Yao Yao , Shi Hong 
Published: February 2024

Abstract
Background
Vitamin D deficiency and systemic inflammation share common pathological mechanisms in muscle loss, cardio-pulmonary function decline, and abnormal metabolism, which are linked to chronic conditions, senescence, and early mortality. However, their combined effect on mortality in older adults has not been well established. This study longitudinal aimed to explore the independent and combined associations of serum 25-hydroxyvitamin D [25(OH)D] and high sensitivity C-reactive protein (hs-CRP) with mortality risk in Chinese community-based older people.

Methods
3072 older adults (86.07 ± 11.87 years, 54.52% female) from the Chinese Longitudinal Healthy Longevity Survey (2012–2018) were enrolled. Baseline 25(OH)D and hs-CRP levels were collected, and survival information was recorded in the 2014 and 2018 follow-up waves. Cox proportional hazard regressions were conducted to explore the associations between 25(OH)D, hs-CRP, and mortality. Demographic characteristics, health behaviors, and chronic disease biomarkers were adjusted.

Results
During 10,622.3 person-years of follow-up (median: 3.51 years), 1321 older adults died, including 448 deaths due to cardiovascular disease (CVD). Increased mortality risk was associated with lower 25(OH)D and higher hs-CRP quantiles, even after adjusting for each other and multiple covariates (all P-trend < 0.05). In combined analyses, the highest all-cause mortality (HR: 2.18, 95% CI: 1.73 ~ 2.56), CVD mortality (HR: 2.30, 95% CI: 1.64 ~ 3.21), and non-CVD mortality (HR: 2.19, 95% CI: 1.79 ~ 2.49) were obtained in participants with both 25(OH)D deficiency (< 50 nmol/L) and high hs-CRP (≥ 3.0 mg/L), respectively. We observed significant additive interactions of 25(OH)D and hs-CRP on all-cause mortality and non-CVD mortality (RERIS>0).

Conclusions
Low 25(OH)D and high hs-CRP, both independently and jointly, increase mortality risk in Chinese community-dwelling older adults. Thus, priority should be given to early detection and appropriate intervention in older individuals with combined vitamin D deficiency and systemic inflammation. Molecular mechanisms of related adverse health effect are worthy of further investigation.
Empyema necessitans caused by methicillin-resistant Staphylococcus aureus: a case report and literature review
Authors: Nakamura Tomoaki , Ishikawa Kazuhiro , Murata Naoki , Sato Kuniko , Kitamura Atsushi , Mori Nobuyoshi , Jinta Torahiko 
Published: February 2024

Abstract
Background
Empyema necessitans (EN) is a rare condition characterized by pleural infection with pus spreading into adjacent soft tissues. Although Mycobacterium tuberculosis and Actinomyces israelii are common causative agents, methicillin-resistant Staphylococcus aureus (MRSA) is relatively rare, but it is associated with high mortality in empyema cases. We aimed to report a unique case of EN caused by MRSA and present a literature review to better understand this rare condition.

Case presentation
A 69-year-old man with a history of right ureteral stone presented with fever and left anterior thoracic pain. A physical examination revealed redness and swelling in the left thoracic region. Imaging studies confirmed EN with fluid accumulation around the sternocostal joint of the left first rib. MRSA was identified from blood and pleural fluid cultures. The patient received antimicrobial therapy, and a chest tube was inserted for drainage. Despite initial improvement, vertebral osteomyelitis was diagnosed on day 17. The antimicrobials were subsequently terminated after 6 weeks, but vertebral osteomyelitis recurred, and treatment was resumed and completed on day 215.

Conclusion
EN caused by MRSA is rare, and the literature review revealed 14 cases from human sources. Positive blood cultures were observed in 40% of cases, and metastatic infections were present in 30% of cases. Osteomyelitis was the most common type of metastatic lesion. All the patients underwent drainage. Patients with MRSA-associated EN frequently develop disseminated lesions and should therefore be carefully examined. Moreover, appropriate treatment with antibiotics and drainage is necessary for a good prognosis. Although the prognosis appeared to be favorable in our review, publication bias and treatment challenges for metastatic infections should be considered.
Should non-invasive prenatal testing be recommended for patients who achieve pregnancy with PGT?
Authors: Liang Yunhao , Li Meiyi , Fei Jia , Chen Zhiheng 
Published: February 2024

Abstract
Objective
To determine whether non-invasive prenatal testing is an alternative testing option to preimplantation genetic testing (PGT) in pregnant patients.

Methods
This was a retrospective study of the clinical outcomes of patients who underwent PGT and invasive or non-invasive pregnancy testing after euploid blastocyst transfer at our IVF centre between January 2017 and December 2022.

Results
In total, 321 patients were enrolled in this study, 138 (43.0%) received invasive pregnancy testing, and 183 (57.0%) patients underwent non-invasive testing. The mean age of the patients in Group 2 was higher than that of the patients in Group 1 (35.64 ± 4.74 vs. 31.04 ± 4.15 years, P < 0.001). The basal LH and AMH levels were higher in Group 1 than in Group 2 (4.30 ± 2.68 vs. 3.40 ± 1.88, P = 0.003; 5.55 ± 11.22 vs. 4.09 ± 3.55, P = 0.012), but the clinical outcomes were not significantly different. Furthermore, the clinical outcomes of patients undergoing invasive testing were similar to those of patients undergoing non-invasive testing with the same PGT indication.

Conclusion
Our results suggest that non-invasive pregnancy testing is a suitable alternative option for detecting the foetal chromosomal status in a PGT cycle. However, the usefulness of non-invasive testing in PGT-M patients is still limited.
The diagnostic potential of miR-196a-1 in colorectal cancer
Authors: Mehrjoei Bayan , Haghnazari Lida , Bashiri Homayoon , Rezvani Nayebali 
Published: February 2024

Abstract
Background
Colorectal cancer (CRC) is a common malignancy worldwide. MicroRNAs (miRNAs) are important epigenetic alterations that notably impact various physiological and pathological processes by acting as negative regulators of gene expression. Furthermore, they have a vital function in different types of cancers, including CRC. In this research, we evaluated, for the very first time, the expression levels of miR-196a-1 in the tissue and plasma of patients with CRC and also homeobox D8 (HOXD8) as the target gene.

Materials and methods
This study included a collection of 220 plasma and tissue samples from 55 patients diagnosed with CRC, as well as 55 healthy individuals matched by age and sex. Total RNA was extracted from plasma and tissue samples, and then polyadenylation and cDNA synthesis were performed. The expression levels of miR-196a-1 and HOXD8 as target gene was evaluated by quantitative RT-PCR (qRT-PCR) assay. We compared the diagnostic value of plasma miR-196a-1 with that of the circulating tumor markers CA19-9 and CEA using a Receiver Operating Characteristics (ROC) analysis. The association of miR-196a-1 with clinicopathological characteristics was assessed in tissue and plasma samples from patients with CRC.

Results
Our data demonstrated that the expression levels of miR-196a-1 in the tissue and plasma samples of CRC patients were 11.426- and 11.655-fold higher, respectively than those in adjacent normal tissue and plasma samples from normal subjects (p < 0.001). Through ROC curve analysis, it was identified that the sensitivity and specificity of miR-196a-1 for tissue samples, with an AUC of 0.925, were 89% and 98%, respectively. In addition, the sensitivity and specificity for plasma samples with an AUC of 0.801 were 70% and 98%, respectively. These findings reveal that miR-196a-1 is a useful biomarker for discriminating cases from controls. Furthermore, the expression of HOXD8 was not significantly altered in tumor tissue samples compared to adjacent normal tissues (P > 0.05).

Conclusions
These results show that miR-196a-1 has an oncogenic impact and plays a significant role in CRC development. The results also indicate that miR-196a-1 could serve as a novel noninvasive biomarker for the detection of CRC.
Psychological pathway to emotional exhaustion among nurses and midwives who provide perinatal bereavement care in China: a path analysis
Authors: Qian Jialu , Wu Gaoyan , Jevitt Cecilia , Sun Shiwen , Wang Man , Sun Xiangyu , Yu Xiaoyan 
Published: February 2024

Abstract
Background
A lack of confidence in perinatal bereavement care (PBC) and the psychological trauma experienced by nurses and midwives during bereavement care leads to their strong need for sufficient organisational support. The current study intended to test a hypothesised model of the specific impact paths among organisational support, confidence in PBC, secondary traumatic stress, and emotional exhaustion among nurses and midwives.

Methods
A descriptive, cross-sectional survey was conducted in sixteen maternity hospitals in Zhejiang Province, China, from August to October 2021. The sample (n = 779) consisted of obstetric nurses and midwives. A path analysis was used to test the relationships among study variables and assess model fit.

Results
Organisational support directly and positively predicted confidence in PBC and demonstrated a direct, negative, and significant association with secondary traumatic stress and emotional exhaustion. Confidence in PBC had a positive direct effect on secondary traumatic stress and a positive indirect effect on emotional exhaustion via secondary traumatic stress. Secondary traumatic stress exhibited a significant, direct effect on emotional exhaustion.

Conclusions
This study shows that nurses' and midwives' confidence in PBC and mental health were leadingly influenced by organisational support in perinatal bereavement practice. It is worth noting that higher confidence in PBC may lead to more serious psychological trauma symptoms in nurses and midwives. Secondary traumatic stress plays an essential role in contributing to emotional exhaustion. The findings suggest that support from organisations and self-care interventions were required to improve confidence in PBC and reduce negative psychological outcomes among those providing PBC. The development of objective measures for assessing competence in PBC and organizational support are essential.
An experimental game to assess hunter’s participation in zoonotic diseases surveillance
Authors: Pouliquen Aude , Mapeyi Gilles Aurélien Boupana , Vanthomme Hadrien , Olive Marie-Marie , Maganga Gaël Darren , Cornelis Daniel , Lebel Sébastien , Peyre Marisa , Delabouglise Alexis 
Published: February 2024

Abstract
Background
Strengthening the surveillance of zoonotic diseases emergence in the wild meat value chains is a critical component of the prevention of future health crises. Community hunters could act as first-line observers in zoonotic pathogens surveillance systems in wildlife, by reporting early signs of the possible presence of a disease in the game animals they observe and manipulate on a regular basis.

Methods
An experimental game was developed and implemented in a forested area of Gabon, in central Africa. Our objective was to improve our understanding of community hunters' decision-making when finding signs of zoonotic diseases in game animals: would they report or dissimulate these findings to a health agency? 88 hunters, divided into 9 groups of 5 to 13 participants, participated in the game, which was run over 21 rounds. In each round the players participated in a simulated hunting trip during which they had a chance of capturing a wild animal displaying clinical signs of a zoonotic disease. When signs were visible, players had to decide whether to sell/consume the animal or to report it. The last option implied a lowered revenue from the hunt but an increased probability of early detection of zoonotic diseases with benefits for the entire group of hunters.

Results
The results showed that false alerts—i.e. a suspect case not caused by a zoonotic disease—led to a decrease in the number of reports in the next round (Odds Ratio [OR]: 0.46, 95% Confidence Interval [CI]: 0.36–0.8, p < 0.01). Hunters who had an agricultural activity in addition to hunting reported suspect cases more often than others (OR: 2.05, 95% CI: 1.09–3.88, p < 0.03). The number of suspect case reports increased with the rank of the game round (Incremental OR: 1.11, CI: 1.06–1.17, p < 0.01) suggesting an increase in participants’ inclination to report throughout the game.

Conclusion
Using experimental games presents an added value for improving the understanding of people’s decisions to participate in health surveillance systems.
Perceptions of barriers to and facilitators of exercise rehabilitation in adults with lung transplantation: a qualitative study in China
Authors: Yang Hui , Liu Saisai , Chen Jingru , Qiao Yaxin , Wang Chengcheng , Zhang Wenping , Wei Li , Chen Ruiyun 
Published: February 2024

Abstract
Background
Exercise is crucial for pulmonary rehabilitation and improving the prognosis of lung transplantation (LTx) patients. However, many LTx patients in China have low exercise tolerance and compliance, and the reasons behind these challenges have not been fully elucidated. Therefore, this qualitative research aims to identify the barriers to and facilitators of exercise rehabilitation in LTx patients.

Methods
From January to July 2023, 15 stable LTx patients were recruited and participated in in-depth, semi-structured, face-to-face interviews at Henan Provincial People’s Hospital. The interview transcripts were analyzed using the COM-B model and the Theoretical Domains Framework (TDF).

Results
Six general themes including 19 barriers and 14 facilitators for the exercise rehabilitation of LTx patients were identified based on the COM-B model and TDF. The barriers to exercise included physical limitations, insufficient exercise endurance, lack of knowledge, and lack of motivation. The facilitators of exercise included motivation, self-efficacy, perceived significance of exercise rehabilitation, and social support.

Conclusion
The study offers detailed insight into the development and implementation of exercise rehabilitation intervention strategies for LTx patients. By combining COM-B model and TDF, the study provides strong evidence that active behavior change strategies are required for LTx patients to promote their participation in exercise rehabilitation. Professional support, pulmonary rehabilitation training, behavior change technology, and digital health tools are essential for strengthening the evidence system for reporting exercise efficacy and effectiveness.
Gender influences resident physicians’ perception of an employee-to-employee recognition program: a mixed methods study
Authors: Tischendorf Jessica S. , Krecko Laura K. , Filipiak Rachel , Osman Fauzia , Zelenski Amy B. 
Published: February 2024

Abstract
Background
Burnout is prevalent in medical training. While some institutions have implemented employee-to-employee recognition programs to promote wellness, it is not known how such programs are perceived by resident physicians, or if the experience differs among residents of different genders.

Methods
We used convergent mixed methods to characterize how residents in internal medicine (IM), pediatrics, and general surgery programs experience our employee-to-employee recognition ("Hi-5″) program. We collected Hi-5s received by residents in these programs from January 1, 2021–December 31, 2021 and coded them for recipient discipline, sex, and PGY level and sender discipline and professional role. We conducted virtual focus groups with residents in each training program.

Main measures and approach
We compared Hi-5 receipt between male and female residents; overall and from individual professions. We submitted focus group transcripts to content analysis with codes generated iteratively and emergent themes identified through consensus coding.

Results
Over a 12-month period, residents received 382 Hi-5s. There was no significant difference in receipt of Hi-5s by male and female residents.
Five IM, 3 surgery, and 12 pediatric residents participated in focus groups. Residents felt Hi-5s were useful for interprofessional feedback and to mitigate burnout. Residents who identified as women shared concerns about differing expectations of professional behavior and communication based on gender, a fear of backlash when behavior does not align with gender stereotypes, and professional misidentification.

Conclusions
The “Hi-5” program is valuable for interprofessional feedback and promotion of well-being but is experienced differently by men and women residents. This limitation of employee-to-employee recognition should be considered when designing equitable programming to promote well-being and recognition.
Optimizing the medical equipment investment in primary care centres in rural China: evidence from a panel threshold model
Authors: Xu Wanchun , Pan Zijing , Zhang Liang , Lu Shan 
Published: February 2024

Abstract
Background
The previous “one-size-fits-all” practice in resource allocation can no longer adapt to the spatial variation in population and health needs. This study aimed to investigate the spatially heterogeneous effect of medical equipment investment in the township health centres in rural China to optimize the investment strategies.

Methods
Based on the national-scale stratified multistage cluster sampling, 319 township health centres from six provinces were included in the study. The retrospective data from 2013 to 2017 were collected for each sampled township health centres and the corresponding township community. The panel threshold regression model was applied to estimate the nonlinear effect of medical equipment increment on the service utilization due to the township communities’ urbanization degree. The influence of township community remoteness on the effects of equipment increment was investigated through subgroup analysis.

Results
Among the township health centres in the neighbouring towns of the county seat (travel time to the county seat < 1 h), the significant effect of medical equipment increment was only found in the township health centres of the towns with high urbanization degrees (the proportion of the residents living in the built-up area > 69.89%), of which the effect size was 774.81 (95% CI 495.63, 1053.98, p < 0.05). Among the township health centres in the remote towns (travel time ≥ 1 h), the effect of medical equipment increment in the township health centres of the low urbanized towns (urban ≤ 5.99%, β = 1052.54, p < 0.01) was around four times the size of that of the counterparts (urban > 5.99%, β = 237.00, p < 0.01).

Conclusion
This study demonstrated the spatially heterogeneous effect of medical equipment investment in the primary care centres in rural China. The priority of the equipment investment was suggested to be given to the township health centres in the remote towns with a low urbanization degree and those in the highly-urbanized neighbouring towns of the county seats.
Substantial health and economic burden of COVID-19 during the year after acute illness among US adults at high risk of severe COVID-19
Authors: Scott Amie , Ansari Wajeeha , Khan Farid , Chambers Richard , Benigno Michael , Di Fusco Manuela , McGrath Leah , Malhotra Deepa , Draica Florin , Nguyen Jennifer , Atkinson Joanna , Atwell Jessica E. 
Published: February 2024

Abstract
Background
Post-COVID conditions encompass a range of long-term symptoms after SARS-CoV-2 infection. The potential clinical and economic burden in the United States is unclear. We evaluated diagnoses, medications, healthcare use, and medical costs before and after acute COVID-19 illness in US patients at high risk of severe COVID-19.

Methods
Eligible adults were diagnosed with COVID-19 from April 1 to May 31, 2020, had ≥ 1 condition placing them at risk of severe COVID-19, and were enrolled in Optum’s de-identified Clinformatics® Data Mart Database for ≥ 12 months before and ≥ 13 months after COVID-19 diagnosis. Percentages of diagnoses, medications, resource use, and costs were calculated during baseline (12 months preceding diagnosis) and the post-acute phase (12 months after the 30-day acute phase of COVID-19). Data were stratified by age and COVID-19 severity.

Results
The cohort included 19,558 patients (aged 18–64 y, n = 9381; aged ≥ 65 y, n = 10,177). Compared with baseline, patients during the post-acute phase had increased percentages of blood disorders (16.3%), nervous system disorders (11.1%), and mental and behavioral disorders (7.7%), along with increases in related prescriptions. Overall, there were substantial increases in inpatient and outpatient healthcare utilization, along with a 23.0% increase in medical costs. Changes were greatest among older patients and those admitted to the intensive care unit for acute COVID-19 but were also observed in younger patients and those who did not require COVID-19 hospitalization.

Conclusions
There is a significant clinical and economic burden of post-COVID conditions among US individuals at high risk for severe COVID-19.