bluuebunny/crossref_metadata_2025_split huggingface dataset:
EBV antibody and gastric cancer risk: a population-based nested case-control study in southern China
Authors: Du Yun , Yu Xia , Chang Ellen T. , Yin Li , Lian Shifeng , Wu Biaohua , Li Fugui , Liang Zhiheng , Zeng Yumei , Chu Bing , Wei Kuangrong , Zhan Jiyun , Liang Xuejun , Ye Weimin , Ji Mingfang 
Published: June 2023

Abstract
Background
We aim to clarify the controversial associations between EBV-related antibodies and gastric cancer risk.

Methods
We analysed the associations between serological Epstein-Barr nuclear antigen 1 immunoglobulin A (EBNA1-IgA) and viral capsid antigen immunoglobulin A (VCA-IgA) by enzyme-linked immunosorbent assay and the risk of gastric cancer in a nested case-control study originated from a population-based nasopharyngeal carcinoma (NPC) screening cohort in Zhongshan, a city of southern China, including 18 gastric cancer cases and 444 controls. Conditional logistic regression was used to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs).

Results
All the sera of cases were sampled before diagnosis and the median time interval was 3.04 (range: 0.04, 7.59) years. Both increased relative optical density (rOD) values of EBNA1-IgA and VCA-IgA were associated with higher risks of gastric cancer with age adjusted ORs of 1.99 (95%CI: 1.07, 3.70) and 2.64 (95%CI: 1.33, 5.23), respectively. Each participant was further classified as high or medium/low risk based on a combination of two anti-EBV antibody levels. Participants in the high-risk group had substantially higher odds of developing gastric cancer than that in the medium/low risk group with an age adjusted OR of 6.53 (95%CI: 1.69, 25.26).

Conclusions
Our research reveals positive associations between EBNA1-IgA and VCA-IgA and gastric cancer risk in southern China. We thus postulate that EBNA1-IgA and VCA-IgA might appear to be potential biomarkers for gastric cancer. More research to further validate the results among diverse populations and investigate its underlying biological mechanism is needed.
An observational cohort study of interstitial lung abnormalities (ILAs) in a large Japanese health screening population (Kumamoto ILA study in Japan: KILA-J)
Authors: Ichikado Kazuya , Ichiyasu Hidenori , Iyonaga Kazuhiro , Kawamura Kodai , Higashi Noritaka , Johkoh Takeshi , Fujimoto Kiminori , Morinaga Jun , Yoshida Minoru , Mitsuzaki Katsuhiko , Suga Moritaka , Tanabe Naoya , Handa Tomohiro , Hirai Toyohiro , Sakagami Takuro 
Published: June 2023

Abstract
Background
Interstitial lung abnormalities (ILAs) are subtle or mild parenchymal abnormalities observed in more than 5% of the lungs on computed tomography (CT) scans in patients in whom interstitial lung disease was not previously clinically suspected and is considered. ILA is considered to be partly undeveloped stages of idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF). This study aims to clarify the frequency of subsequent IPF or PPF diagnosis, the natural course from the preclinical status of the diseases, and the course after commencing treatment.

Methods
This is an ongoing, prospective, multicentre observational cohort study of patients with ILA referred from general health screening facilities with more than 70,000 annual attendances. Up to 500 participants will be enrolled annually over 3 years, with 5-year assessments every six months. Treatment intervention including anti-fibrotic agents will be introduced in disease progression cases. The primary outcome is the frequency of subsequent IPF or PPF diagnoses. Additionally, secondary and further endpoints are associated with the efficacy of early therapeutic interventions in cases involving disease progression, including quantitative assessment by artificial intelligence.

Discussion
This is the first prospective, multicentre, observational study to clarify (i) the aetiological data of patients with ILA from the largest general health check-up population, (ii) the natural course of IPF or PPF from the asymptomatic stage, and (iii) the effects and outcomes of early therapeutic intervention including anti-fibrotic agents for progressive cases of ILA. The results of this study could significantly impact the clinical practice and treatment strategy for progressive fibrosing interstitial lung diseases.

Trial registration number
UMIN000045149.
A predictive scoring system for postoperative delirium in the elderly patients with intertrochanteric fracture
Authors: Hu Yunjiu , Yang Mingming 
Published: June 2023

Abstract
Objective
To establish a scoring system to predict the postoperative delirium in elderly patients with intertrochanteric fracture.

Materials and methods
We retrospectively reviewed 159 elderly patients with a diagnosis of intertrochanteric fracture and underwent closed reduction and intramedullary nail fixation, and then divided them into two groups including the delirium group (23 cases) or non-delirium group (136 cases) in our hospital from January 2017 to December 2019. The following clinical characteristics were recorded and analyzed: age, gender, fracture classification, body mass index (BMI), history of diabetes mellitus, history of stroke, preoperative albumin, preoperative hemoglobin (Hb), preoperative arterial partial pressure of oxygen (PaO2), time between admission and surgery, lower limb thrombosis, American Society of Anesthesiologists (ASA) grade, operative time, operative blood loss, and intraoperative blood transfusion. The prevalence of these clinical characteristics in delirium group was evaluated, and the scoring system was established using logistic regression analysis. The performance of the scoring system was also prospectively validated.

Results
The predictive scoring system was based on five clinical characteristics confirmed as significant predictors of postoperative delirium, namely, age > 75 years, history of stroke, preoperative Hb ≤ 100 g/L, preoperative PaO2 ≤ 60 mmHg, and time between admission to surgery > 3 days. Delirium group showed a significant higher score than non-delirium (6.26 vs. 2.29, P < 0.001), and the optimal cut-off value for the scoring system was 4 points. The sensitivity and specificity of the scoring system for predicting postoperative delirium were 82.61% and 81.62% in derivation set, respectively, and 72.71% and 75.00% in validation set.

Conclusion
The predictive scoring system confirmed with achieve satisfactory sensitivity and specificity in predicting postoperative delirium in the elderly with intertrochanteric fracture. The risk of postoperative delirium in patients with the score of 5 to 11 is high, while the score of 0 to 4 is low.
Comparison of the cox regression to machine learning in predicting the survival of anaplastic thyroid carcinoma
Authors: Xu Lizhen , Cai Liangchun , Zhu Zheng , Chen Gang 
Published: June 2023

Summary
Background
To compare the ability of the Cox regression and machine learning algorithms to predict the survival of patients with Anaplastic thyroid carcinoma (ATC).

Methods
Patients diagnosed with ATC were extracted from the Surveillance, Epidemiology, and End Results database. The outcomes were overall survival (OS) and cancer-specific survival (CSS), divided into: (1) binary data: survival or not at 6 months and 1 year; (2): time-to-event data. The Cox regression method and machine learnings were used to construct models. Model performance was evaluated using the concordance index (C-index), brier score and calibration curves. The SHapley Additive exPlanations (SHAP) method was deployed to interpret the results of machine learning models.

Results
For binary outcomes, the Logistic algorithm performed best in the prediction of 6-month OS, 12-month OS, 6-month CSS, and 12-month CSS (C-index = 0.790, 0.811, 0.775, 0.768). For time-event outcomes, traditional Cox regression exhibited good performances (OS: C-index = 0.713; CSS: C-index = 0.712). The DeepSurv algorithm performed the best in the training set (OS: C-index = 0.945; CSS: C-index = 0.834) but performs poorly in the verification set (OS: C-index = 0.658; CSS: C-index = 0.676). The brier score and calibration curve showed favorable consistency between the predicted and actual survival. The SHAP values was deployed to explain the best machine learning prediction model.

Conclusions
Cox regression and machine learning models combined with the SHAP method can predict the prognosis of ATC patients in clinical practice. However, due to the small sample size and lack of external validation, our findings should be interpreted with caution.
Operationalizing risk-appropriate perinatal care in a rural US State: directions for policy and practice
Authors: Holman Carly , Glover Annie , Fertaly Kaitlin , Nelson Megan 
Published: June 2023

Abstract
Background

Risk-appropriate care improves outcomes by ensuring birthing people and infants receive care at a facility prepared to meet their needs. Perinatal regionalization has particular importance in rural areas where pregnant people might not live in a community with a birthing facility or specialty care. Limited research focuses on operationalizing risk-appropriate care in rural and remote settings. Through the implementation of the Centers for Disease Control and Prevention (CDC) Levels of Care Assessment Tool (LOCATe), this study assessed the system of risk-appropriate perinatal care in Montana.

Methods
Primary data was collected from Montana birthing facilities that participated in the CDC LOCATe version 9.2 (collected July 2021 – October 2021). Secondary data included 2021 Montana birth records. All birthing facilities in Montana received an invitation to complete LOCATe. LOCATe collects information on facility staffing, service delivery, drills, and facility-level statistics. We added additional questions on transport.

Results
Nearly all (96%) birthing facilities in Montana completed LOCATe (N = 25). The CDC applied its LOCATe algorithm to assign each facility with a level of care that aligns directly with guidelines published by the American Academy of Pediatrics (AAP) and the American College of Obstetricians and Gynecologists (ACOG), and Society for Maternal-Fetal Medicine (SMFM). LOCATe-assessed levels for neonatal care ranged from Level I to Level III. Most (68%) facilities LOCATe-assessed at Level I or lower for maternal care. Close to half (40%) self-reported a higher-level of maternal care than their LOCATe-assessed level, indicating that many facilities believe they have greater capacity than outlined in their LOCATe-assessed level. The most common ACOG/SMFM requirements contributing to the maternal care discrepancies were the lack of obstetric ultrasound services and a physician anesthesiologist.

Conclusions
The Montana LOCATe results can drive broader conversations on the staffing and service requirements necessary to provide high-quality obstetric care in low-volume rural hospitals. Montana hospitals often rely on Certified Registered Nurse Anesthetists (CRNA) for anesthesia services and telemedicine to access specialty providers. Integrating a rural health perspective into the national guidelines could enhance the utility of LOCATe to support state strategies to improve the provision of risk-appropriate care.
Applying a data-driven population segmentation approach in German claims data
Authors: Pioch Carolina , Henschke Cornelia , Lantzsch Hendrikje , Busse Reinhard , Vogt Verena 
Published: June 2023

Abstract
Background
Segmenting the population into homogenous groups according to their healthcare needs may help to understand the population’s demand for healthcare services and thus support health systems to properly allocate healthcare resources and plan interventions. It may also help to reduce the fragmented provision of healthcare services. The aim of this study was to apply a data-driven utilisation-based cluster analysis to segment a defined population in the south of Germany.

Methods
Based on claims data of one big German health insurance a two-stage clustering approach was applied to group the population into segments. A hierarchical method (Ward's linkage) was performed to determine the optimal number of clusters, followed by a k-means cluster analysis using age and healthcare utilisation data in 2019. The resulting segments were described in terms of their morbidity, costs and demographic characteristics.

Results
The 126,046 patients were divided into six distinct population segments. Healthcare utilisation, morbidity and demographic characteristics differed significantly across the segments. The segment “High overall care use” comprised the smallest share of patients (2.03%) but accounted for 24.04% of total cost. The overall utilisation of services was higher than the population average. In contrast, the segment “Low overall care use” included 42.89% of the study population, accounting for 9.94% of total cost. Utilisation of services by patients in this segment was lower than population average.

Conclusion
Population segmentation offers the opportunity to identify patient groups with similar healthcare utilisation patterns, patient demographics and morbidity. Thereby, healthcare services could be tailored for groups of patients with similar healthcare needs.
Genome-wide DNA methylation profiling of CD4+ T lymphocytes identifies differentially methylated loci associated with adult primary refractory immune thrombocytopenia
Authors: Du Hanzhi , Tang Qinghua , Yang Jian , Yan Bin , Yang Lihong , Wang Mengchang 
Published: June 2023

Abstract
Background
DNA methylation played a crucial role in the pathogenesis of immune thrombocytopenia (ITP). However, genome-wide DNA methylation analysis has not been applied thus far. The present study aimed to provide the first DNA methylation profiling for ITP.

Methods
Peripheral blood CD4+ T lymphocytes samples were collected from 4 primary refractory ITP cases and 4 age-matched healthy controls, and DNA methylome profiling was performed using Infinium MethylationEPIC BeadChip. Differentially methylated CpG sites were further validated in another independent cohort of 10 ITP patients and 10 healthy controls using qRT-PCR.

Results
The DNA methylome profiling identified a total of 260 differentially methylated CpG sites mapping to 72 hypermethylated and 64 hypomethylated genes. These genes were mainly enriched in the actin nucleation of the Arp2/3 complex, vesicle transport, histone H3-K36 demethylation, Th1 and Th2 cell differentiation, and Notch signaling pathway according to the GO and KEGG databases. The mRNA expression of CASP9, C1orf109, and AMD1 were significantly different.

Conclusions
Given the altered DNA methylation profiling of ITP, our study provides new insights into its genetic mechanism and suggests candidate biomarkers for the diagnosis and treatment of ITP.
Protein length distribution is remarkably uniform across the tree of life
Authors: Nevers Yannis , Glover Natasha M. , Dessimoz Christophe , Lecompte Odile 
Published: June 2023

Abstract
Background
In every living species, the function of a protein depends on its organization of structural domains, and the length of a protein is a direct reflection of this. Because every species evolved under different evolutionary pressures, the protein length distribution, much like other genomic features, is expected to vary across species but has so far been scarcely studied.

Results
Here we evaluate this diversity by comparing protein length distribution across 2326 species (1688 bacteria, 153 archaea, and 485 eukaryotes). We find that proteins tend to be on average slightly longer in eukaryotes than in bacteria or archaea, but that the variation of length distribution across species is low, especially compared to the variation of other genomic features (genome size, number of proteins, gene length, GC content, isoelectric points of proteins). Moreover, most cases of atypical protein length distribution appear to be due to artifactual gene annotation, suggesting the actual variation of protein length distribution across species is even smaller.

Conclusions
These results open the way for developing a genome annotation quality metric based on protein length distribution to complement conventional quality measures. Overall, our findings show that protein length distribution between living species is more uniform than previously thought. Furthermore, we also provide evidence for a universal selection on protein length, yet its mechanism and fitness effect remain intriguing open questions.
Fermentation quality and bacterial community of delayed filling stylo silage in response to inoculating lactic acid bacteria strains and inoculating time
Authors: Tian Jing , Huang Liying , Tian Rong , Wu Juanyan , Tang Ruxue , Zhang Jianguo 
Published: June 2023

Abstract
Background
Filling silos generally takes much time in practice, which may negatively affect silage fermentation and feed intake. To clarify the effects of inoculating time, lactic acid bacteria (LAB) strains and filling time on the silage fermentation and microbes of stylo (Stylosanthes guianensis) and its silage, ensiling was quickly performed (quickly filling, QF) with or without LAB (Lactobacillus plantarum SXC48, Lb. plantarum CCZZ1 and Enterococcus faecalis XC124), and was performed after stylo inoculated with or without LAB was placed for 1 day (delayed filling, DF1) and 2 days (DF2).

Results
Delayed filling significantly increased pH, buffering capacity, microbial counts and lactic acid, acetic acid and NH3–N contents of stylo prior to ensiling. Inoculating Lb. plantarum SXC48 and CCZZ1 improved the fermentation quality of QF silage, indicated by more lactic acid, as well as lower pH and butyric acid content. Inoculating time significantly affected the pH and lactic acid content of silages. For the DF2 silages, inoculating SXC48 at filling was better than at chopping, while inoculating CCZZ1 had good fermentation quality, regardless of inoculating time. The results of 16S rRNA sequencing indicated that delayed filling enhanced the bacterial diversity of materials and silage, and inoculating significantly changed the composition of silage microbes. Kosakonia, Pseudomonas and Pantoea jointly dominated the fresh material, while Pantoea and Lelliottia jointly dominated the DF2 material. For the QF silages, inoculating SXC48 and CCZZ1 increased the relative abundance of Lactobacillus from 16.4% in the control silage to 76.5% and 82.0%, respectively. Pantoea and Lelliottia jointly dominated the DF silages. Inoculating SXC48 and CCZZ1 also increased the relative abundance of Lactobacillus in the DF stylo silages.

Conclusions
Under the present research conditions, delayed filling increased the lactic acid content and reduced the acetic acid, propionic acid and NH3–N contents of stylo silage, however, increased the bacterial diversity and relative abundance of undesirable bacteria, such as Pantoea and Lelliottia. The inoculating effectiveness varied with the LAB strains and inoculating time. Inoculating strian SXC48 at filling was better than at chopping, while inoculating strian CCZZ1 at both chopping and filling obtained the similar benefit.

Graphical Abstract
Associations between common mental disorders and menopause: cross-sectional analysis of the 2014 Adult Psychiatric Morbidity Survey
Authors: Adji Amira , Rhead Rebecca , McManus Sally , Shoham Natalie 
Published: June 2023

Summary
We investigated whether women who participated in a household survey in England were more likely to screen positive for possible generalised anxiety disorder and depression during and after menopause. We used logistic regression in secondary cross-sectional analyses of 1413 participants from the 2014 Adult Psychiatric Morbidity Survey data, adjusting for potential confounders (including age, deprivation score and chronic disease).
We found that participants who were post-menopausal were more likely to screen positive for possible depression compared with participants who were pre-menopausal (3.9% v. 1.7%; adjusted odds ratio 3.91, 95% CI 1.23–12.46), but there was no association with perimenopause. We found no evidence of an association between menopausal stage and possible generalised anxiety disorder or symptom score. Clinicians should be aware of the association between menopause and depression, to best support women. Future research could focus on to what extent associations are driven by somatic features, and how this might be modified.
Association of tertiary lymphoid structures with outcomes from PD-1 inhibition in advanced malignant pleural mesothelioma.
Authors: Homicsko Krisztian , Zygoura Giota , Tissot Stephanie , Popat Sanjay , Curioni-Fontecedro Alessandra , Dellaporta Tereza , O'Brien Mary , Pope Anthony , Shah Riyaz N.H. , Kammler Rosita , Finn Stephen P. , Coukos George , Peters Solange , Stahel Rolf A. 
Published: June 2023

e20545 Background: Predictive biomarkers of benefit form immunotherapy in malignant mesothelioma patients remain poorly defined. The 9-15 PROMISE-MESO study (NCT02991482) of the European Thoracic Oncology Platform (ETOP) evaluated second-line pembrolizumab against chemotherapy. Pembrolizumab led to an increased response rate compared to chemotherapy, which did not translate to survival benefits. We evaluated if the presence of tertiary lymphoid structures (TLSs) with different compositions or LRRC15+ immune suppressive fibroblasts could predict the clinical benefit from pembrolizumab. Methods: We performed multiplex immune histochemistry analysis on tumor tissues. 144 patients were included in the clinical trial, from whom, 112 had available tumor tissue for analysis: 55 patients in the chemotherapy arm, and 57 patients in the immune therapy arm. We performed the following panel: calretinin or WT1 (mesothelioma cells), CD20, CD23, CD11c, LRRC15, aSMA, and DAPI. We used the Akoya Vectra Polaris platform for analysis. The IFQuant analytical pipeline developed at the Swiss Institute for Bioinformatics (SIB) was used for analyses. Results: We defined three categories of TLSs: general CD20+ TLSs independent of other markers. CD20/CD23 double-positive as mature TLSs (mTLS), and TLSs with dendritic cells (CD11c+, cTLS). Immune suppressive CAFs were defined as LRRC15+ cells/mm2. CD20+ TLSs were identified in 84% of patients' stroma, with a median of 21 TLSs/tumor tissue and 2 TLSs/mm2. mTLSs were rare, only detected in 10 of the 112 patients (9%). cTLSs with dendritic cells were more frequent and present in 45% of all patients (50/112), and roughly half of the TLS+ patients (53%) had CD11c+ cells detected in TLSs. LRRC15+ cancer-associated fibroblasts (CAFs) were detected in 85% of patients, with a median density of 61 cells/mm2. LRRC15- tumors also contained TLSs but had significantly fewer than LRRC15+ tumors (p = 0.0079). We did not find any significant association between the responses or PFS with TLS, mTLS, and LRRC15+ CAFs. We found inverse association between cTLS levels and response to immune therapy (p = 0.037) but not for PFS. Conclusions: Our data shows that advanced malignant mesotheliomas frequently harbor TLSs, but these TLSs are mostly not activated/mature. The absence of antigen-presenting cells in TLSs, like CD11c dendritic cells, is unexpectedly associated with increased response to pembrolizumab. The high prevalence of immune suppressive LRRC15+ CAFs might explain the low response rate to pembrolizumab and could be linked to the absence of maturation of TLSs. Clinical trial information: EudraCT number: 2016-002062-31 .