bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of GVHD prophylaxis on CMV reactivation and disease after HLA-matched peripheral blood stem cell transplantation
Authors: Ueda Oshima Masumi , Xie Hu , Zamora Danniel , Flowers Mary E. , Hill Geoffrey R. , Mielcarek Marco B. , Sandmaier Brenda M. , Gooley Ted A. , Boeckh Michael J. 
Published: January 2023

Abstract
The kinetics of early and late cytomegalovirus (CMV) reactivation after hematopoietic cell transplantation using various methods of graft-versus-host-disease (GVHD) prophylaxis are poorly defined. We retrospectively compared CMV reactivation and disease among 780 seropositive patients given HLA-matched peripheral blood stem cell (PBSC) grafts and calcineurin inhibitor plus posttransplantation cyclophosphamide (PTCy; n = 44), mycophenolate mofetil (MMF; n = 414), or methotrexate (MTX; n = 322). Transplantation occurred between 2007 and 2018; CMV monitoring/management followed uniform standard practice. Hazards of CMV reactivation at various thresholds were compared. Spline curves were fit over average daily viral load and areas under the curve (AUC) within 1 year were calculated. PTCy and MMF were associated with an increased risk of early (day ≤100) CMV reactivation ≥250 IU/mL after multivariate adjustment. The viral load AUC at 1 year was highest with MMF (mean difference = 0.125 units vs MTX group) and similar between PTCy and MTX (mean difference = 0.016 units vs MTX group). CMV disease risk was similar across groups. There was no interaction between GVHD prophylaxis and CMV reactivation on chronic GVHD risk. Despite PTCy-associated increased risk of early CMV reactivation, the CMV disease risk by 1 year was low in HLA-matched PBSC transplant recipients. In contrast, MMF was associated with higher overall CMV viral burden in the 1 year posttransplant. Although different mechanisms of immunosuppressive agents may affect CMV reactivation risk, effective prevention of GVHD may reduce corticosteroid exposure and mitigate infection risk over time.
SN38-loaded nanomedicine mediates chemo-radiotherapy against CD44-expressing cancer growth
Authors: Yang Shu-Jyuan , Pai Jui-An , Yao Cheng-Jung , Huang Chung-Huan , Chen Jenny Ling‑Yu , Wang Chung-Hao , Chen Ke-Cheng , Shieh Ming-Jium 
Published: January 2023

Abstract
Background
Chemo-radiotherapy is the combined chemotherapy and radiotherapy on tumor treatment to obtain the local radiosensitization and local cytotoxicity of the tumor and to control the microscopic metastatic disease.

Methods
In this study, 7-ethyl-10-hydroxycamptothecin (SN38) molecules could be successfully loaded into human serum albumin (HSA)–hyaluronic acid (HA) nanoparticles (SH/HA NPs) by the hydrophobic side groups of amino acid in HSA.

Results
HSA could be used to increase the biocompatibility and residence time of the nanoparticles in the blood, whereas HA could improve the benefits and overall treatment effect on CD44-expressing colorectal cancer (CRC), and reduce drug side effects. In addition to its role as a chemotherapeutic agent, SN38 could be used as a radiosensitizer, able to arrest the cell cycle, and allowing cells to stay in the G2/M stage, to improve the sensitivity of tumor cells to radiation. In vivo results demonstrated that SH/HA NPs could accumulate in the tumor and produce significant tumor suppression, with no adverse effects observed when combined with γ-ray irradiation. This SH/HA NPs-medicated chemo-radiotherapy could induce an anti-tumor immune response to inhibit the growth of distal tumors, and produce an abscopal effect.

Conclusions
Therefore, this SN38-loaded and HA-incorporated nanoparticle combined with radiotherapy may be a promising therapeutic artifice for CRC in the future.
Evaluation of automatic discrimination between benign and malignant prostate tissue in the era of high precision digital pathology
Authors: Zhdanovich Yauheniya , Ackermann Jörg , Wild Peter J. , Köllermann Jens , Bankov Katrin , Döring Claudia , Flinner Nadine , Reis Henning , Wenzel Mike , Höh Benedikt , Mandel Philipp , Vogl Thomas J. , Harter Patrick , Filipski Katharina , Koch Ina , Bernatz Simon 
Published: January 2023

Abstract
Background
Prostate cancer is a major health concern in aging men. Paralleling an aging society, prostate cancer prevalence increases emphasizing the need for efficient diagnostic algorithms.

Methods
Retrospectively, 106 prostate tissue samples from 48 patients (mean age, $$66\pm 6.6$$

66
±
6.6

years) were included in the study. Patients suffered from prostate cancer (n = 38) or benign prostatic hyperplasia (n = 10) and were treated with radical prostatectomy or Holmium laser enucleation of the prostate, respectively. We constructed tissue microarrays (TMAs) comprising representative malignant (n = 38) and benign (n = 68) tissue cores. TMAs were processed to histological slides, stained, digitized and assessed for the applicability of machine learning strategies and open–source tools in diagnosis of prostate cancer. We applied the software QuPath to extract features for shape, stain intensity, and texture of TMA cores for three stainings, H&E, ERG, and PIN-4. Three machine learning algorithms, neural network (NN), support vector machines (SVM), and random forest (RF), were trained and cross-validated with 100 Monte Carlo random splits into 70% training set and 30% test set. We determined AUC values for single color channels, with and without optimization of hyperparameters by exhaustive grid search. We applied recursive feature elimination to feature sets of multiple color transforms.

Results
Mean AUC was above 0.80. PIN-4 stainings yielded higher AUC than H&E and ERG. For PIN-4 with the color transform saturation, NN, RF, and SVM revealed AUC of $$0.93\pm 0.04$$

0.93
±
0.04

, $$0.91\pm 0.06$$

0.91
±
0.06

, and $$0.92\pm 0.05$$

0.92
±
0.05

, respectively. Optimization of hyperparameters improved the AUC only slightly by 0.01. For H&E, feature selection resulted in no increase of AUC but to an increase of 0.02–0.06 for ERG and PIN-4.

Conclusions
Automated pipelines may be able to discriminate with high accuracy between malignant and benign tissue. We found PIN-4 staining best suited for classification. Further bioinformatic analysis of larger data sets would be crucial to evaluate the reliability of automated classification methods for clinical practice and to evaluate potential discrimination of aggressiveness of cancer to pave the way to automatic precision medicine.
Uncovering novel MHC alleles from RNA-Seq data: expanding the spectrum of MHC class I alleles in sheep
Authors: Buitkamp Johannes 
Published: January 2023

Abstract
Background
Major histocompatibility complex (MHC) class I glycoproteins present selected peptides or antigens to CD8 + T cells that control the cytotoxic immune response. The MHC class I genes are among the most polymorphic loci in the vertebrate genome, with more than twenty thousand alleles known in humans. In sheep, only a very small number of alleles have been described to date, making the development of genotyping systems or functional studies difficult. A cost-effective way to identify new alleles could be to use already available RNA-Seq data from sheep. Current strategies for aligning RNA-Seq reads against annotated genome sequences or transcriptomes fail to detect the majority of class I alleles. Here, I combine the alignment of RNA-Seq reads against a specific reference database with de novo assembly to identify alleles. The method allows the comprehensive discovery of novel MHC class I alleles from RNA-Seq data (DinoMfRS).

Results
Using DinoMfRS, virtually all expressed MHC class I alleles could be determined. From 18 animals 75 MHC class I alleles were identified, of which 69 were novel. In addition, it was shown that DinoMfRS can be used to improve the annotation of MHC genes in the sheep genome sequence.

Conclusions
DinoMfRS allows for the first time the annotation of unknown, more divergent MHC alleles from RNA-Seq data. Successful application to RNA-Seq data from 16 animals has approximately doubled the number of known alleles in sheep. By using existing data, alleles can now be determined very inexpensively for populations that have not been well studied. In addition, MHC expression studies or evolutionary studies, for example, can be greatly improved in this way, and the method should be applicable to a broader spectrum of other multigene families or highly polymorphic genes.
European Cohorts of patients and schools to Advance Response to Epidemics (EuCARE): a cluster randomised interventional and observational study protocol to investigate the relationship between schools and SARS-CoV-2 infection
Authors: Raimondi Sara , Gandini Sara , Rubio Quintanares Gibran Horemheb , Abecasis Ana , Lopalco Pier Luigi , D’Ecclesiis Oriana , Chiocca Susanna , Tomezzoli Elisa , Cutica Ilaria , Mazzoni Davide , Amparo Nuno , Pingarilho Marta , Carmagnola Daniela , Dellavia Claudia , Zuccotti Gianvincenzo , Ronchini Chiara , Bellerba Federica , Dewald Felix , Kaiser Rolf , Incardona Francesca ,   The Eucare WP4
Published: January 2023

Abstract
Background
Contradictory results were reported on the role of school closure/reopening on the overall SARS-CoV-2 transmission rate, as well as on which kind and level of mitigation measures implemented in schools may be effective in limiting its diffusion. Some recent studies were reassuring, showing that opening did not increase the community spread, although teachers and families are worried about the high class density. On the other hand, distance learning was associated with a negative impact on learning, sociability and psychological health, especially in vulnerable children. As it becomes clear that the SARS-CoV-2 pandemic will last for a long time, there is a high need for studies and solutions to support safe schools opening based on scientific evidence of harms and benefits. The Lolli-Methode (LM) is a strategy for epidemiological surveillance and early intervention aiming at SARS-CoV-2 outbreaks’ reduction in schools, relying on polymerase chain reaction analysis of saliva samples.

Methods
In this cluster randomised trial protocol, we aim to determine whether the LM is useful to support schools opening and to reduce clusters and attack rates in schools, compared with the standard of care (SoC) surveillance by public health departments. This multicenter study will enrol 440 classes (around 8800 students, teachers and other personnel) from two countries, cluster randomised to LM or SoC. The samples from the pools will be collected and tested using PCR-based techniques. Test results will be combined with questionnaires filled in by children, parents, schoolteachers, and principals, concerning ongoing mitigation measures, their perceived psychological impact and other health and socio-economic information. An ancillary observational study will be carried out to study the prevalence of SARS-CoV-2 in schools, frequencies and size of clusters and attack rates, to compare the effectiveness of the different preventive measures adopted and to evaluate psychological issues in students and teachers in relation to the pandemic’s containment measures.

Discussion

By the end of this study, we will have defined and characterised the applicability of the LM for SARS-CoV-2 surveillance, as well as the impact of pandemic preventive measures on children and teachers.
Trial registration International Standard Randomised Controlled Trial Number: NCT05396040, 27.05.2022.
Identification of a prognostic six-immune-gene signature and a nomogram model for uveal melanoma
Authors: Yang Binghua , Fan Yuxia , Liang Renlong , Wu Yi , Gu Aiping 
Published: January 2023

Abstract
Background
To identify an immune-related prognostic signature and find potential therapeutic targets for uveal melanoma.

Methods
The RNA-sequencing data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The prognostic six-immune-gene signature was constructed through least absolute shrinkage and selection operator and multi-variate Cox regression analyses. Functional enrichment analysis and single sample GSEA were carried out. In addition, a nomogram model established by integrating clinical variables and this signature risk score was also constructed and evaluated.

Results
We obtained 130 prognostic immune genes, and six of them were selected to construct a prognostic signature in the TCGA uveal melanoma dataset. Patients were classified into high-risk and low-risk groups according to a median risk score of this signature. High-risk group patients had poorer overall survival in comparison to the patients in the low-risk group (p < 0.001). These findings were further validated in two external GEO datasets. A nomogram model proved to be a good classifier for uveal melanoma by combining this signature. Both functional enrichment analysis and single sample GSEA analysis verified that this signature was truly correlated with immune system. In addition, in vitro cell experiments results demonstrated the consistent trend of our computational findings.

Conclusion
Our newly identified six-immune-gene signature and a nomogram model could be used as meaningful prognostic biomarkers, which might provide uveal melanoma patients with individualized clinical prognosis prediction and potential novel treatment targets.
Risky sexual behavior and self-rated mental health among young adults in Skåne, Sweden – a cross-sectional study
Authors: Karle Anna , Agardh Anette , Larsson Markus , Arunda Malachi Ochieng 
Published: January 2023

Abstract
Background
Risky sexual behavior is a public health challenge that significantly affects young people’s health and well-being in Sweden and throughout the world. Moreover, poor mental health, anxiety and depression among adolescents and young adults have increased in recent years. However, although hypothesized, the associations between general mental health and risky sexual behavior among young adults are less established. Thus, this study aimed to examine the association between self-rated mental health and risky sexual behavior among young adults in southern Sweden.

Methods
Population-based, cross-sectional survey data from 2968 participants aged 18–30 years old residing in southern Sweden was used (response rate 42%). The survey included questions on sexual behavior, alcohol habits, sociodemographic background, and mental health. Logistic regression was used to examine the associations between mental health, depression, anxiety, and risky sexual behavior, stratified by sex (gender). Indicators for risky sexual behavior included not using a condom, non-condom use with casual partner, and multiple (≥2) sexual partners during the last year.

Results
Generally, male participants rated their depression and anxiety levels considerably lower than their female counterparts. Poor mental health, high depression, and high anxiety scores (levels) were significantly associated with having multiple sexual partners among among female participants; adjusted odds ratios (aOR) was 1.3 (95% CI 1.01 to 1.71). However, findings among males were not statistically significant. Furthermore, overall results indicated that higher depression and anxiety scores were associated with 1.4 and 1.6 higher odds, respectively, of not using condom with a casual partner in the most recent sexual encounter. Similarly, higher anxiety scores were associated with non-condom use in the latest sexual encounter, aOR 1.4 (1.1–1.7), but no significant gender-specific associations were found.

Conclusion
The associations found between poor mental health factors and multiple sex partners among females warrant consideration in future public health interventions. Further research to increase the understanding of the causal mechanisms that link mental health factors and risky sexual behavior, especially multiple sex partners, among young adult females is needed to support evidence-based interventions.
Perceived COVID-19 susceptibility and preventive behaviors: moderating effects of social support in Italy and South Korea
Authors: An Soontae , Schulz Peter J. , Kang Hannah 
Published: January 2023

Abstract
Background
The COVID-19 pandemic hit Italy much harder than South Korea. As a way of explaining the different impact in the two countries, this study examines the moderating role of social support on the relationship between perceived susceptibility and preventive behaviors in the two countries.

Methods
Surveys were conducted in South Korea (n = 1396) and Italy (n = 487) of participants aged 50 to 89 years.

Results
South Koreans felt higher levels of perceived social support than their Italian counterparts. As would be expected, greater perceived susceptibility was associated with increased preventive behavior. Furthermore, a significant three-way interaction effect was found for perceived susceptibility, social support, and country. For Italians, a person who feels him/herself highly susceptible will increase preventive behaviors, if there is a lot of social support. On the other hand, for South Koreans, those with a low level of susceptibility perform more preventive measures than people with a high level of susceptibility if there is a lot of social support.

Conclusions
This study provides insights into how cognitive factors, such as susceptibility and severity, as well as social and environmental factors can be taken into account, and the public be told the real risk and given behavioral guidelines when a pandemic is approaching. Given the critical role of social support as a coping mechanism in crisis situations, societies should mull over ways to increase emotional and instrumental support.
Effect of EDDY and manual dynamic activation techniques on postoperative pain in non-surgical retreatment: a randomized controlled trial
Authors: İnce-Yusufoğlu Selen , Keskin Neslihan Büşra , Uslu Gülşah , Helvacioglu-Yigit Dilek 
Published: January 2023

AbstractBackgroundDuring non-surgical retreatment process, the products such as dentin debris, root canal fillings, irrigation solutions, microorganisms and remaining pulp tissues can extrude to the apical area and can cause the postoperative pain and flare-up. Thus, the aim of this study was to evaluatethe effect of EDDY and manual dynamic activation (MDA) techniques on postoperative pain (PP) associated with retreatment.MethodsNinety patients scheduled for retreatment were treated at a single visit. Non-vital mandibular premolar teeth diagnosed with asymptomatic apical periodontitis were included in this study. The patients were divided into two groups (n = 45) on the basis of the need for additional irrigation activation procedures (EDDY and MDA). The patients’ post-treatment pain levels were asked to rate the intensity of their pain on a 10-point numerical rating scale (NRS) at the 12th, 24th, 48th, and 72nd h and 7 days.The data were analyzed using the chi-square and Wilcoxon signed-rank test was used for within-group comparisons and Mann Whitney U test was used to compare the groups by time period.ResultsThe difference in postoperative pain intensity between two groups was statistically significant at 12, 24, 48, and 72 h (p < 0.05). There was no significant difference at 7 days. Moreover, no statistically significant difference was found between the two groups in terms of gender and analgesic medication intake (p > 0.05). Pain intensity after the treatment was lesser in the MDA groupthanin the EDDY group at 12, 24, 48, and 72 h.ConclusionThis study could lead us to conclude that the two activation systems can be used during endodontic retreatment with no difference at PP 7 days later. However, a comparison of the groups indicated that the EDDY resulted in significantly more PP at 12, 24, 48, and 72 h.Trial registration ClinicalTrials.gov Identifier: NCT04726670.
Association between history of childbirth and chronic, functionally significant back pain in later life
Authors: Zhang Michelle , Cooley Corinne , Ziadni Maisa S. , Mackey Ian , Flood Pamela 
Published: January 2023

Abstract
Background
Back pain is more prevalent among women than men. The association with sex could be related to pregnancy and childbirth, unique female conditions. This association has not been thoroughly evaluated.

Methods
Using a retrospective cohort design, we evaluated the relationship between history of childbirth on the prevalence and severity of functionally consequential back pain in 1069 women from a tertiary care pain management clinic. Interactions among preexisting, acute peripartum, and subsequent back pain were evaluated as secondary outcomes among the parous women using logistic and linear regression as appropriate.

Results
The women who had given birth had a higher risk for functionally significant back pain compared to women who had not given birth (85% vs 77%, p < 0.001, Risk Ratio 1.11 [1.04-1.17]). The association was preserved after correction for age, weight, and race. Back pain was also more slightly severe (Numerical Rating Score for Pain 7[5-8] vs 6[5-7] out of 10, p = 0.002). Women who recalled severe, acute postpartum back pain had a higher prevalence of current debilitating back pain (89% vs 75%, Risk Ratio 1.19 (1.08-1.31), p = 0.001). Twenty-eight percent of acute postpartum back pain never resolved and 40% reported incomplete resolution.

Conclusions
A history of pregnancy and childbirth is a risk factor for chronic functionally significant back pain in women. Severe acute postpartum back pain is a risk factor for future disability suggesting that the peripartum period may provide an important opportunity for intervention. Early recognition and management may mitigate future disability.

Trial registration
The study was registered with clinicaltrials.gov as “Association Between Chronic Headache and Back Pain with Childbirth” (NCT04091321) on 16/09/2019 before it was initiated.
Promoting physician-patient language concordance in undergraduate medical education: a peer assisted learning approach
Authors: Ismaiel Sawsan , AlGhafari Dana , Ibrahim Halah 
Published: January 2023

AbstractBackgroundVerbal communication plays an important role in the patient-physician relationship. Research shows that language concordance, when a healthcare professional communicates fluently in the patient’s preferred language, contributes to patient satisfaction and improves healthcare outcomes. Yet, many medical schools worldwide, including most institutions in the Arab world, use English as the language of instruction. As a result, students lack confidence and feel unprepared to communicate effectively with the local population. This manuscript describes the development, implementation and early perceptions of an Arabic language program for medical students in the United Arab Emirates.MethodsIn 2020, the learning communities at Khalifa University College of Medicine and Health Sciences launched a pilot program implementing a Peer Assisted Learning (PAL) framework to teach Arabic medical terminology and language to both native and non-native Arabic speaking medical students. A web-based survey was administered to the first two cohorts of students to assess satisfaction with the classes and the program’s impact on students’ communication skills during clinical encounters.ResultsEarly perceptions of the program were very positive, with 43/48 students (89.6%) reporting that they used the information during home visits and clinical rotations, and 42 students (87.5%) admitting that the classes made them feel more comfortable in communicating with the Arabic speaking local patient population.ConclusionThis paper explores a new educational approach to address the challenge of language barriers in healthcare. A feasible, low cost program using peer assisted learning can improve students’ comfort in communicating with patients in the local language.