bluuebunny/crossref_metadata_2025_split huggingface dataset:
Symptomatic MERS-CoV infection reduces the risk of future COVID-19 disease; a retrospective cohort study
Authors: El-Saed Aiman , Othman Fatmah , Baffoe-Bonnie Henry , Almulhem Rawabi , Matalqah Muayed , Alshammari Latifah , Alshamrani Majid M. 
Published: November 2023

Abstract
Background
The general human immune responses similarity against different coronaviruses may reflect some degree of cross-immunity, whereby exposure to one coronavirus may confer partial immunity to another. The aim was to determine whether previous MERS-CoV infection was associated with a lower risk of subsequent COVID-19 disease and its related outcomes.

Methods
We conducted a retrospective cohort study among all patients screened for MERS-CoV at a tertiary care hospital in Saudi Arabia between 2012 and early 2020. Both MERS-CoV positive and negative patients were followed up from early 2020 to September 2021 for developing COVID-19 infection confirmed by RT-PCR testing.

Results
A total of 397 participants followed for an average 15 months during COVID-19 pandemic (4.9 years from MERS-CoV infection). Of the 397 participants, 93 (23.4%) were positive for MERS-CoV at baseline; 61 (65.6%) of the positive cases were symptomatic. Out of 397, 48 (12.1%) participants developed COVID-19 by the end of the follow-up period. Cox regression analysis adjusted for age, gender, and major comorbidity showed a marginally significant lower risk of COVID-19 disease (hazard ratio = 0.533, p = 0.085) and hospital admission (hazard ratio = 0.411, p = 0.061) in patients with positive MERS-CoV. Additionally, the risk of COVID-19 disease was further reduced and became significant in patients with symptomatic MERS-CoV infection (hazard ratio = 0.324, p = 0.034) and hospital admission (hazard ratio = 0.317, p = 0.042).

Conclusions
The current findings may indicate a partial cross-immunity, where patients with symptomatic MERS-CoV have a lower risk of future COVID-19 infection and related hospitalization. The present results may need further examination nationally using immunity markers.
A deep-learning approach for segmentation of liver tumors in magnetic resonance imaging using UNet++
Authors: Wang Jing , Peng Yanyang , Jing Shi , Han Lujun , Li Tian , Luo Junpeng 
Published: November 2023

Abstract
Objective
Radiomic and deep learning studies based on magnetic resonance imaging (MRI) of liver tumor are gradually increasing. Manual segmentation of normal hepatic tissue and tumor exhibits limitations.

Methods
105 patients diagnosed with hepatocellular carcinoma were retrospectively studied between Jan 2015 and Dec 2020. The patients were divided into three sets: training (n = 83), validation (n = 11), and internal testing (n = 11). Additionally, 9 cases were included from the Cancer Imaging Archive as the external test set. Using the arterial phase and T2WI sequences, expert radiologists manually delineated all images. Using deep learning, liver tumors and liver segments were automatically segmented. A preliminary liver segmentation was performed using the UNet + + network, and the segmented liver mask was re-input as the input end into the UNet + + network to segment liver tumors. The false positivity rate was reduced using a threshold value in the liver tumor segmentation. To evaluate the segmentation results, we calculated the Dice similarity coefficient (DSC), average false positivity rate (AFPR), and delineation time.

Results
The average DSC of the liver in the validation and internal testing sets was 0.91 and 0.92, respectively. In the validation set, manual and automatic delineation took 182.9 and 2.2 s, respectively. On an average, manual and automatic delineation took 169.8 and 1.7 s, respectively. The average DSC of liver tumors was 0.612 and 0.687 in the validation and internal testing sets, respectively. The average time for manual and automatic delineation and AFPR in the internal testing set were 47.4 s, 2.9 s, and 1.4, respectively, and those in the external test set were 29.5 s, 4.2 s, and 1.6, respectively.

Conclusion
UNet + + can automatically segment normal hepatic tissue and liver tumors based on MR images. It provides a methodological basis for the automated segmentation of liver tumors, improves the delineation efficiency, and meets the requirement of extraction set analysis of further radiomics and deep learning.
COVID-19 contact tracing at work in Belgium - how tracers tweak guidelines for the better
Authors: Kieltyka Jerome , Ghattas Jinane , Ruppol Sandrine , Nicaise Pablo , Raymenants Joren , Speybroeck Niko 
Published: November 2023

AbstractBackgroundWhen conducting COVID-19 contact tracing, pre-defined criteria allow differentiating high-risk contacts (HRC) from low-risk contacts (LRC). Our study aimed to evaluate whether contact tracers in Belgium followed these criteria in practice and whether their deviations improved the infection risk assessment.MethodWe conducted a retrospective cohort study in Belgium, through an anonymous online survey, sent to 111,763 workers by email. First, we evaluated the concordance between the guideline-based classification of HRC or LRC and the tracer’s classification. We computed positive and negative agreements between both. Second, we used a multivariate Poisson regression to calculate the risk ratio (RR) of testing positive depending on the risk classification by the contact tracer and by the guideline-based risk classification.ResultsFor our first research question, we included 1105 participants. The positive agreement between the guideline-based classification in HRC or LRC and the tracer’s classification was 0.53 (95% CI 0.49–0.57) and the negative agreement 0.70 (95% CI: 0.67–0.72). The type of contact tracer (occupational doctors, internal tracer, general practitioner, other) did not significantly influence the results. For the second research question, we included 589 participants. The RR of testing positive after an HRC compared to an LRC was 3.10 (95% CI: 2.71–3.56) when classified by the contact tracer and 2.24 (95% CI: 1.94–2.60) when classified by the guideline-based criteria.ConclusionOur study indicates that contact tracers did not apply pre-defined criteria for classifying high and low risk contacts. Risk stratification by contact tracers predicts who is at risk of infection better than guidelines only. This result indicates that a knowledgeable tracer can target testing better than a general guideline, asking for a debate on how to adapt the guidelines.
Psychosocial work environment and mental health among the global workforce of seafarers in the wake of the COVID-19 pandemic
Authors: Hayes-Mejia Rebecca , Stafström Martin 
Published: November 2023

Abstract
Background
The aim of this study was to investigate the impact of the COVID-19 pandemic on the mental health outcomes of international seafarers, who played a crucial role in maintaining global trade during the pandemic. The study examined how changes in psychosocial work environment and policies affected mental health outcomes among seafarers.

Methods
We analyzed a survey including answers from 17,861 seafarers, serving on 44 different international commercial vessels with 154 different nationalities. Stress, anxiety, and depression were applied as outcome measures in this study. Three sets of independent variables were included; work-related consequences of the COVID-19 pandemic, general psychosocial work environment onboard, and socioeconomic variables. First, we applied binary linear regression, followed by a multivariate linear regression analysis.

Results
The study found that changes in safety consciousness and clear communication from employers were associated with better mental health outcomes among seafarers. Eroded policies related to crew changes had a significant negative effect on mental wellbeing due to delays caused by national quarantine guidelines and travel restrictions. The results also showed a discrepancy in mental health outcomes between those onboard and those onshore, with stress being present in both groups.

Conclusions
The findings suggest that crisis management within shipping companies played an important role in mitigating adverse mental health outcomes during the pandemic. Clear communication from employers and emphasizing safety issues onboard were effective strategies for promoting better mental wellbeing among seafarers. However, delays in crew changes had a significant negative impact on mental health outcomes, highlighting the need for global cooperation and overarching agreements to protect international seafarers during times of crises.
Application value of triglyceride-glucose index and triglyceride-glucose body mass index in evaluating the degree of hepatic steatosis in non-alcoholic fatty liver disease
Authors: Wang Mengyuan , Chang Mingxing , Shen Peipu , Wei Wei , Li Huayao , Shen Guifang 
Published: November 2023

Abstract
Background
The elevation of TyG is considered an important factor in promoting the progression of non-alcoholic fatty liver disease (NAFLD), but its impact on the degree of liver steatosis remains unclear. This study aims to explore the relationship between TyG and TyG-related indices, such as triglyceride glucose-body mass index (TyG-BMI), with the degree of liver fat accumulation.

Methods
From January 2021 to March 2022, 1171 participants underwent health check-ups, and all underwent FibroScan transient elastography. The analysis focused on identifying the factors that contribute to the onset of NAFLD and the degree of hepatic steatosis.

Results
The predictive value of TyG-BMI (OR = 1.039, 95% CI 1.031–1.046) in triggering NAFLD development was greater than that of TyG alone. The areas under the curve for TyG-BMI and TyG were calculated at 0.808 and 0.720, respectively. TyG-BMI (OR = 1.034, P < 0.001) was identified as a main independent factor affecting hepatic steatosis severity. With each incremental increase in TyG-BMI, the likelihood of experiencing an increase in the extent of hepatic steatosis was 1.034 times higher than that of the preceding unit.

Conclusions
The TyG-BMI showed higher accuracy in predicting NAFLD than did the TyG, and was more closely linked to the severity of hepatic steatosis. Therefore, it can be included as a parameter in health management centers and should be widely used to screen and evaluate patients with NAFLD.
Probing milk extracellular vesicles for intestinal delivery of RNA therapies
Authors: Zhang Yunyue , Belaid Mona , Luo Xiang , Daci Armond , Limani Rinë , Mantaj Julia , Zilbauer Matthias , Nayak Komal , Vllasaliu Driton 
Published: November 2023

Abstract
Background
Oral delivery remains unattainable for nucleic acid therapies. Many nanoparticle-based drug delivery systems have been investigated for this, but most suffer from poor gut stability, poor mucus diffusion and/or inefficient epithelial uptake. Extracellular vesicles from bovine milk (mEVs) possess desirable characteristics for oral delivery of nucleic acid therapies since they both survive digestion and traverse the intestinal mucosa.

Results
Using novel tools, we comprehensively examine the intestinal delivery of mEVs, probing whether they could be used as, or inform the design of, nanoparticles for oral nucleic acid therapies. We show that mEVs efficiently translocate across the Caco-2 intestinal model, which is not compromised by treatment with simulated intestinal fluids. For the first time, we also demonstrate transport of mEVs in novel 3D ‘apical-out’ and monolayer-based human intestinal epithelial organoids (IEOs). Importantly, mEVs loaded with small interfering RNA (siRNA) induced (glyceraldehyde 3-phosphate dehydrogenase, GAPDH) gene silencing in macrophages. Using inflammatory bowel disease (IBD) as an example application, we show that administration of anti-tumour necrosis factor alpha (TNFα) siRNA-loaded mEVs reduced inflammation in a IBD rat model.

Conclusions
Together, this work demonstrates that mEVs could either act as natural and safe systems for oral delivery or nucleic acid therapies, or inform the design of synthetic systems for such application.

Graphical Abstract
Arterial thrombosis triggered by methotrexate-induced hyperhomocysteinemia in a systemic lupus erythematosus patient with antiphospholipid antibodies
Authors: Schiavi Chiara , Marri Luca , Negrini Simone 
Published: November 2023

AbstractSystemic lupus erythematosus (SLE) patients have an increased risk of cardiovascular disease and thrombotic events, and the presence of antiphospholipid antibodies further raises the risk of these complications. Here we report a case of a patient with SLE and triple positivity for antiphospholipid antibodies who developed a popliteal artery thrombosis in the context of a severe hyperhomocysteinemia after the introduction of methotrexate (MTX) treatment. MTX is one of the most prescribed medications for a wide spectrum of autoimmune diseases, including SLE. On the other hand, by interfering with folate metabolism, it may induce hyperhomocysteinemia, which, in turn, may increase the risk of vascular complications. Current recommendations suggest screening and, when possible, treating classical and disease-related cardiovascular risk factors in all lupus patients. Based on what observed in our case, we suggest a follow-up of homocysteine levels after the introduction of drugs capable of inducing hyperhomocysteinemia, such as MTX, in SLE patients at high cardiovascular risk.
BRD4/nuclear PD-L1/RelB circuit is involved in the stemness of breast cancer cells
Authors: Kim Su-Lim , Choi Hack Sun , Lee Dong-Sun 
Published: November 2023

Abstract
Background
Breast cancer (BC) is the most common cancer diagnosed in women worldwide. BC stem cells (BCSCs) have been known to be involved in the carcinogenesis of the breast and contribute to therapeutic resistance. The programmed death-ligand 1 (PD-L1) expression of BC correlated with a poor prognosis. Immunotherapies that target PD-L1 have great potential and have been successful when applied to cancer treatment. However, whether PD-L1 regulates BCSC formation is unknown.

Methods
BCSCs were enriched by serum-free suspension culture. The properties of BCSCs were examined by mammosphere formation assay, CD44+/Cd24−, aldehyde dehydrogenase (ALDH) assay, CSC marker analysis, and mammosphere growth assay. To elucidate the functions of bromodomain-containing protein 4 (BRD4), nuclear PD-L1, and RelB proteins in the stemness of BCSCs, mammosphere formation was examined using BRD4 inhibitor and degrader, PD-L1 degrader, and RelB inhibitor. The antitumor function of 3',4',7,8-tetrahydroxyflavone (THF), a specific BRD4 inhibitor, was studied through in vivo tumor model and mouse studies, and the protein levels of c-Myc, PD-L1, and RelB were examined in tumor model under THF treatment.

Results
BRD4 was upregulated in breast CSCs and regulates the stemness of BCs. The downregulation of BRD4 using BRD4 PROTAC, ARV-825, and BRD4 inhibitor, (+)-JQ1, inhibits mammosphere formation and reduces the levels of breast CSC markers (CD44+/CD24− and ALDH1), stem cell marker genes, and mammosphere growth. BRD4 inhibitor (JQ1) and degrader (ARV825) downregulate membrane and nuclear fractions of PD-L1 through the inhibition of PD-L1 transcript levels. The knockdown of PD-L1 inhibits mammosphere formation. Verteporfin, a PD-L1 degrader, inhibits the transcripts and protein levels of PD-L1 and downregulates the transcript and protein levels of RelB. Calcitriol, a RelB inhibitor, and the knockdown of RelB using si-RelB regulate mammosphere formation through interleukin-6 (IL-6) expression. THF is a natural product and a potent selective BRD4 inhibitor, inhibits mammosphere formation, and reduces the levels of CD44+/CD24− and mammosphere growth by downregulating c-Myc, PD-L1, and RelB. 3',4',7,8-THF shows tumoricidal activity and increased levels of CD3+CD4+ and CD3+CD8+ T-cells in the tumor and tumor-draining lymph nodes (TDLNs) in the murine tumor model using 4T1 and MC38 cells.

Conclusions
The results show the first evidence of the essential role of the BRD4/nuclear PD-L1/RelB axis in breast CSC formation. The nuclear PD-L1 regulates RelB, and the RelB/p65 complex induces IL6 and breast CSC formation. Targeting nuclear PD-L1 represents a potential and novel tool for immunotherapies of intractable BC.
Anaplastic thyroid cancer cells reduce CD71 levels to increase iron overload tolerance
Authors: D’Aprile Simona , Denaro Simona , Pavone Anna Maria , Giallongo Sebastiano , Giallongo Cesarina , Distefano Alfio , Salvatorelli Lucia , Torrisi Filippo , Giuffrida Raffaella , Forte Stefano , Tibullo Daniele , Li Volti Giovanni , Magro Gaetano , Vicario Nunzio , Parenti Rosalba 
Published: November 2023

Abstract
Background
Follicular thyroid cancer (FTC) is a prevalent form of differentiated thyroid cancer, whereas anaplastic thyroid cancer (ATC) represents a rare, fast-growing, undifferentiated, and highly aggressive tumor, posing significant challenges for eradication. Ferroptosis, an iron-dependent cell death mechanism driven by the excessive production of reactive oxygen species and subsequent lipid peroxidation, emerges as a promising therapeutic strategy for cancer. It has been observed that many cancer cells exhibit sensitivity to ferroptosis, while some other histotypes appear to be resistant, by counteracting the metabolic changes and oxidative stress induced by iron overload.

Methods
Here we used human biopsies and in vitro approaches to analyse the effects of iron-dependent cell death. We assessed cell proliferation and viability through MTT turnover, clonogenic assays, and cytofluorimetric-assisted analysis. Lipid peroxidation assay and western blot were used to analyse molecular mechanisms underlying ferroptosis modulation. Two distinct thyroid cancer cell lines, FTC-133 (follicular) and 8505C (anaplastic), were utilized. These cell lines were exposed to ferroptosis inducers, Erastin and RSL3, while simulating an iron overload condition using ferric ammonium citrate.

Results
Our evidence suggests that FTC-133 cell line, exposed to iron overload, reduced their viability and showed increased ferroptosis. In contrast, the 8505C cell line seems to better tolerate ferroptosis, responding by modulating CD71, which is involved in iron internalization and seems to have a role in resistance to iron overload and consequently in maintaining cell viability.

Conclusions
The differential tolerance to ferroptosis observed in our study may hold clinical implications, particularly in addressing the unmet therapeutic needs associated with ATC treatment, where resistance to ferroptosis appears more pronounced compared to FTC.
Comparative analysis of soil organic matter fractions, lability, stability ratios, and carbon management index in various land use types within bharatpur catchment, Chitwan District, Nepal
Authors: Murindangabo Yves Theoneste , Kopecký Marek , Hoang Trong Nghia , Bernas Jaroslav , Parajuli Tulsi , Dhakal Suman , Konvalina Petr , UFITIKIREZI Jean de Dieu Marcel , Kaneza Gisele , Khanal Babu Ram , Dhakal Shiva Chandra , Shrestha Arjun Kumar 
Published: November 2023

Abstract
Background
Land use and land cover changes have a significant impact on the dynamics of soil organic matter (SOM) and its fractions, as well as on overall soil health. This study conducted in Bharatpur Catchment, Chitwan District, Nepal, aimed to assess and quantify variations in total soil organic matter (TSOMC), labile organic matter fraction (CL), stable organic matter fraction (CS), stability ratio (SR), and carbon management index (CMI) across seven land use types: pastureland, forestland, fruit orchards, small-scale conventional agricultural land, large-scale conventional agricultural land, large-scale alternative fallow and conventional agricultural land, and organic farming agricultural land. The study also explored the potential use of the Carbon Management Index (CMI) and stability ratio (SR) as indicators of soil degradation or improvement in response to land use changes.

Results
The findings revealed significant differences in mean values of TSOMC, CL, and CS among the different land use types. Forestland and organic farming exhibited significantly higher TSOMC (3.24%, 3.12%) compared to fruit orchard lands (2.62%), small scale conventional farming (2.22%), alternative fallow and conventional farming (2.06%), large scale conventional farming (1.84%) and pastureland (1.20%). Organic farming and Forestland also had significantly higher CL (1.85%, 1.84%) and CS (1.27%, 1.39%) compared to all other land use types. Forest and organic farming lands showed higher CMI values, while pastures and forests exhibited higher SR values compared to the rest of the land use types.

Conclusions
This study highlights the influence of various land use types on soil organic matter pools and demonstrates the potential of CMI and SR as indicators for assessing soil degradation or improvement in response to land use and land cover changes.
Bone marrow from periacetabular osteotomies as a novel source for human mesenchymal stromal cells
Authors: Handke Maximilian , Rakow Anastasia , Singer Debora , Miebach Lea , Schulze Frank , Bekeschus Sander , Schoon Janosch , Wassilew Georgi I. 
Published: November 2023

Abstract
Background
Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are used in regenerative medicine and related research involving immunomodulatory, anti-inflammatory, anti-fibrotic and regenerative functions. Isolation of BM-MSCs from samples obtained during total hip arthroplasty (THA) is routinely possible. Advanced age and comorbidities of the majority of patients undergoing THA limit their applicability. Our study aimed to evaluate the potential of bone marrow obtained during periacetabular osteotomy (PAO) as a novel source of BM-MSCs from young donors by analyzing cell yield and cell characteristics.

Methods
Bone samples were obtained from the anterior Os ilium or superior Os pubis during PAO and from the femoral cavity during primary THA. Isolation of bone marrow-derived mononuclear cells (BM-MNCs) was performed by density gradient centrifugation. The samples from PAO and THA patients were compared in terms of BM-MSC yield, colony formation and the proportion of BM-MSCs within the BM-MNC population using flow cytometry analysis. The cells were characterized based on the expression of BM-MSC-specific surface markers. The functionality of the cells was compared by quantifying post-thaw viability, metabolic activity, proliferation capacity, senescence-associated beta galactosidase (SA-β-gal) expression, trilineage differentiation potential and major secretome proteins.

Results
Isolation of BM-MNCs was possible in a reliable and reproducible manner when using bone from PAO containing more than 0.24 g bone marrow. PAO patients were younger than patients of the THA group. Bone obtained during PAO contained less bone marrow and led to a lower BM-MSC number after the first cell culture passage compared to BM-MSCs obtained during THA. BM-MSCs from PAO samples are characterized by a higher proliferation capacity. This results in a higher yield in cell culture passage two, when normalized to the sample weight. BM-MSCs from PAO patients showed increased secretion of TGF-β1, TIMP2, and VEGF upon osteogenic differentiation. BM-MSCs from PAO and THA patients revealed similar results regarding the onset of SA-β-gal expression and trilineage differentiation capacity.

Conclusions
We suggest that bone obtained during PAO is a promising novel source for BM-MSCs from young donors. Limited absolute cell yield due to low sample weight must be considered in early cell culture passages and might be critical for the range of clinical applications possible for BM-MSCs from this source. The higher proliferation capacity and increased growth factor secretion of BM-MSCs from young donors may be beneficial for future regenerative cell therapies, in vitro models, and tissue engineering.