bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dirichlet process mixture models to impute missing predictor data in counterfactual prediction models: an application to predict optimal type 2 diabetes therapy
Authors: Cardoso Pedro , Dennis John M. , Bowden Jack , Shields Beverley M. , McKinley Trevelyan J. ,   the MASTERMIND Consortium
Published: January 2024

Abstract
Background
The handling of missing data is a challenge for inference and regression modelling. A particular challenge is dealing with missing predictor information, particularly when trying to build and make predictions from models for use in clinical practice.

Methods
We utilise a flexible Bayesian approach for handling missing predictor information in regression models. This provides practitioners with full posterior predictive distributions for both the missing predictor information (conditional on the observed predictors) and the outcome-of-interest. We apply this approach to a previously proposed counterfactual treatment selection model for type 2 diabetes second-line therapies. Our approach combines a regression model and a Dirichlet process mixture model (DPMM), where the former defines the treatment selection model, and the latter provides a flexible way to model the joint distribution of the predictors.

Results
We show that DPMMs can model complex relationships between predictor variables and can provide powerful means of fitting models to incomplete data (under missing-completely-at-random and missing-at-random assumptions). This framework ensures that the posterior distribution for the parameters and the conditional average treatment effect estimates automatically reflect the additional uncertainties associated with missing data due to the hierarchical model structure. We also demonstrate that in the presence of multiple missing predictors, the DPMM model can be used to explore which variable(s), if collected, could provide the most additional information about the likely outcome.

Conclusions
When developing clinical prediction models, DPMMs offer a flexible way to model complex covariate structures and handle missing predictor information. DPMM-based counterfactual prediction models can also provide additional information to support clinical decision-making, including allowing predictions with appropriate uncertainty to be made for individuals with incomplete predictor data.
The impact of night shift stress and sleep disturbance on nurses quality of life: case in Palestine Red Crescent and Al-Ahli Hospital
Authors: AL-hrinat Jebril , Al-Ansi Abdullah M. , Hendi Aseel , Adwan Ghadeer , Hazaimeh Manar 
Published: January 2024

Abstract
Background
Nurses play a vital role in providing round-the-clock care to patients, but the challenges associated with working night shifts can have significant implications for their well-being and quality of life.

Methods
This cross-sectional study aimed to investigate the impact of night shift stress and sleep disturbance on the quality of life among nurses working in Palestine Red Crescent Society and Al-Ahli Hospital. Convenience sampling was used to recruit 189 full-time registered nurses with at least one year of job experience. The participants completed a questionnaire assessing night shift stress, sleep disturbance, and quality of life. Descriptive statistics, correlation analysis, and path analysis were conducted to analyze the data.

Results
The results reveal that quality of life has positive and low relationship with both night shift stress and sleep disturbances. Results also reveal that night shift stress had a direct negative impact on the quality of life of nurses. Sleep disturbance was found to mediate the relationship between night shift stress and quality of life, indicating that higher levels of night shift stress were associated with increased sleep disturbance, which, in turn, led to poorer quality of life outcomes.

Conclusion
These findings highlight the importance of addressing night shift stress and sleep disturbance among nurses to enhance their well-being and improve the quality of care provided to patients. In conclusion, this study contributes to the existing literature by demonstrating the detrimental effects of night shift stress and sleep disturbance on the quality of life of nurses. It emphasizes the importance of implementing interventions and creating supportive work environments that address the unique challenges faced by nurses working night shifts.
Comparing microbiotas of foals and their mares’ milk in the first two weeks after birth
Authors: Mienaltowski Michael J. , Callahan Mitchell , De La Torre Ubaldo , Maga Elizabeth A. 
Published: January 2024

Abstract
Background
The mare-foal relationship is essential for the well-being and growth of a foal. Mare’s milk provides a foal with nutrients, protective immunity, and microbes. Within the first two weeks of life, there is a risk for a foal to suffer from diarrhea, particularly “foal heat diarrhea” which happens at about the time of a mare’s estrus cycle but is more likely due to transitions in the microbiota in the foal’s gastrointestinal (GI) tract. We hypothesized that this GI microbiota transition could be caused by changes in lysozyme and microbial populations in the mare’s milk. To test this hypothesis, fifteen mare-foal pairs were followed in the first 15 days post-foaling. Every other day milk was collected from mares and rectal swabs were collected from foals. Lysozyme activity in the mare’s milk was measured using a fluorescence assay. Microbial DNA was isolated from the milk and swabs and the V4 domain of 16 S rRNA genes were PCR amplified and sequenced using Illumina MiSeq technology. Microbial populations were analyzed using DADA2 and phyloseq within R.

Results
Mare’s milk lysozyme activity peaked for samples at Day 1 and levels dropped to 72.5% of Day 1 activity by Day 15; however, microbial populations in the mare’s milk did not vary significantly over the two weeks. Furthermore, levels of microbial diversity found in foal rectal swabs were initially similar to microbial diversity seen in mare’s milk; however, over the first fifteen days, diversity increased for the foal rectal swab microbiota and swab microbial populations differed from milk microbes. A transition occurred shifting from microbes from the phylum Proteobacteria early in rectal swabs to those primarily from the phyla Firmicutes and Bacteroidota after the first few days post-foaling. These phyla contained several families and genera of microbes that promote utilization of milk components in healthy gut transition. Microbial abundance levels correlated more with days post-parturition than with lysozyme activity and mare’s milk microbial populations.

Conclusions
The findings suggest that much of the microbial populations responsible for the transition of the foal’s gut comes from sources outside of mare’s milk species and levels of lysozyme activity.
A novel prognostic signature and therapy guidance for hepatocellular carcinoma based on STEAP family
Authors: Fu Dongxue , Zhang Xian , Zhou Yi , Hu Shanshan 
Published: January 2024

Abstract
Background
The six-transmembrane epithelial antigen of prostate (STEAP) family members are known to be involved in various tumor-related biological processes and showed its huge potential role in tumor immunotherapy.

Methods
Biological differences were investigated through Gene set enrichment analysis (GSEA) and tumor microenvironment analysis by CIBERSORT. Tumor mutation burden (TMB), immunotherapy response and chemotherapeutic drugs sensitivity were estimated in R.

Results
We established a prognostic signature with the formula: risk score = STEAP1 × 0.3994 + STEAP4 × (− 0.7596), which had a favorable concordance with the prediction. The high-risk group were enriched in cell cycle and RNA and protein synthesis related pathways, while the low-risk group were enriched in complement and metabolic related pathways. And the risk score was significantly correlated with immune cell infiltration. Most notably, the patients in the low-risk group were characterized with increased TMB and decreased tumor immune dysfunction and exclusion (TIDE) score, indicating that these patients showed better immune checkpoint blockade response. Meanwhile, we found the patients with high-risk were more sensitive to some drugs related to cell cycle and apoptosis.

Conclusions
The novel signature based on STEAPs may be effective indicators for predicting prognosis, and provides corresponding clinical treatment recommendations for HCC patients based on this classification.
Immune checkpoint inhibitors in gastrointestinal malignancies: an Umbrella review
Authors: Noori Maryam , Jafari-Raddani Farideh , Davoodi-Moghaddam Zeinab , Delshad Mahda , Safiri Saeid , Bashash Davood 
Published: January 2024

AbstractIn the Modern era, immune checkpoint inhibitors (ICIs) have been the cornerstone of success in the treatment of several malignancies. Despite remarkable therapeutic advances, complex matrix together with significant molecular and immunological differences have led to conflicting outcomes of ICI therapy in gastrointestinal (GI) cancers. As far we are aware, to date, there has been no study to confirm the robustness of existing data, and this study is the first umbrella review to provide a more comprehensive picture about ICIs’ efficacy and safety in GI malignancies. Systematic search on PubMed, Scopus, Web of Science, EMBASE, and Cochrane library identified 14 meta-analyses. The pooled analysis revealed that ICIs application, especially programmed death-1 (PD-1) inhibitors such as Camrelizumab and Sintilimab, could partially improve response rates in patients with GI cancers compared to conventional therapies. However, different GI cancer types did not experience the same efficacy; it seems that hepatocellular carcinoma (HCC) and esophageal cancer (EC) patients are likely better candidates for ICI therapy than GC and CRC patients. Furthermore, application of ICIs in a combined-modal strategy are perceived opportunity in GI cancers. We also assessed the correlation of PD-L1 expression as well as microsatellite status with the extent of the response to ICIs; overall, high expression of PD-L1 in GI cancers is associated with better response to ICIs, however, additional studies are required to precisely elaborate ICI responses with respect to microsatellite status in different GI tumors. Despite encouraging ICI efficacy in some GI cancers, a greater number of serious and fatal adverse events have been observed; further highlighting the fact that ICI therapy in GI cancers is not without cost, and further studies are required to utmost optimization of this approach in GI cancers.
A serum panel of three microRNAs may serve as possible biomarkers for kidney renal clear cell carcinoma
Authors: Wen Zhenyu , Li Yingqi , Zhao Zhengping , Li Rongkang , Li Xinji , Lu Chong , Sun Chen , Chen Wenkang , Ge Zhenjian , Ni Liangchao , Lai Yongqing 
Published: January 2024

Abstract
Background
Although non-invasive radiological techniques are widely applied in kidney renal clear cell carcinoma (KIRC) diagnosis, more than 50% of KIRCs are detected incidentally during the diagnostic procedures to identify renal cell carcinoma (RCC). Thus, sensitive and accurate KIRC diagnostic methods are required. Therefore, in this study, we aimed to identify KIRC-associated microRNAs (miRNAs).

Methods
This three-phase study included 224 participants (112 each of patients with KIRC and healthy controls (NCs)). RT-qPCR was used to evaluate miRNA expression in KIRC and NC samples. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to predict the usefulness of serum miRNAs in KIRC diagnosis. In addition, we performed survival and bioinformatics analyses.

Results
We found that miR-1-3p, miR-129-5p, miR-146b-5p, miR-187-3p, and miR-200a-3p were significantly differentially expressed in patients with KIRC. A panel consisting of three miRNAs (miR-1-3p, miR-129-5p, and miR-146b-5p) had an AUC of 0.895, ranging from 0.848 to 0.942. In addition, using the GEPIA database, we found that the miRNAs were associated with CREB5. According to the survival analysis, miR-146b-5p overexpression was indicative of a poorer prognosis in patients with KIRC.

Conclusions
The identified three-miRNA panel could serve as a non-invasive indicator for KIRC and CREB5 as a potential target gene for KIRC treatment.
Lipid changes during endocrine therapy in early-stage breast cancer patients: A real-world study
Authors: Li Yuechong , Deng Zixi , Wang Yingjiao , Shen Songjie 
Published: January 2024

Abstract
Background
Endocrine drugs may affect lipid metabolism in breast cancer (BC) patients. This study explores lipid changes in early-stage BC patients taking different endocrine drugs.

Methods
The changing trend of blood lipid during endocrine therapy in 2756 BC patients from January 2013 to December 2021 was retrospectively analyzed. The changes in four lipid parameters were assessed by the Generalized Linear Mixed Model, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C). These parameters were quantified at baseline and at 6, 12, 18, 24, 36, 48, 60, and 72 months after endocrine therapy initiation. Furthermore, a subgroup analysis according to menopausal status or medication types was conducted.

Results
A total of 1201 patients taking aromatase inhibitors (AIs), including anastrozole (ANA), letrozole (LET), or exemestane (EXE), and 1555 patients taking toremifene (TOR) were enrolled. TC and TG levels showed a significantly elevated trend during 5 years of treatment (P < 0.05). HDL-C levels increased from baseline in the TOR group (P < 0.05). Compared with the postmenopausal AI group, the increasing trends of TC, TG, and LDL-C in the premenopausal AI group were more evident with the extension of time (β = 0.105, 0.027, 0.086, respectively). Within 3 years, TC, TG, and LDL-C levels in the ANA and LET groups were significantly higher than baseline (P < 0.05). Moreover, the levels of TG in the EXE group were significantly lower than that in the ANA or LET group (P < 0.05), but this significant difference disappeared after 3 years.

Conclusions
AIs significantly influenced lipid profiles more than TOR. AIs had a greater effect on blood lipids in premenopausal patients. Steroidal AIs (EXE) may affect lipid levels less than nonsteroidal AIs (ANA and LET).
Recent trends in preparation and biomedical applications of iron oxide nanoparticles
Authors: Meng Yu Qing , Shi Ya Nan , Zhu Yong Ping , Liu Yan Qing , Gu Li Wei , Liu Dan Dan , Ma Ang , Xia Fei , Guo Qiu Yan , Xu Cheng Chao , Zhang Jun Zhe , Qiu Chong , Wang Ji Gang 
Published: January 2024

AbstractThe iron oxide nanoparticles (IONPs), possessing both magnetic behavior and semiconductor property, have been extensively used in multifunctional biomedical fields due to their biocompatible, biodegradable and low toxicity, such as anticancer, antibacterial, cell labelling activities. Nevertheless, there are few IONPs in clinical use at present. Some IONPs approved for clinical use have been withdrawn due to insufficient understanding of its biomedical applications. Therefore, a systematic summary of IONPs’ preparation and biomedical applications is crucial for the next step of entering clinical practice from experimental stage. This review summarized the existing research in the past decade on the biological interaction of IONPs with animal/cells models, and their clinical applications in human. This review aims to provide cutting-edge knowledge involved with IONPs’ biological effects in vivo and in vitro, and improve their smarter design and application in biomedical research and clinic trials.
Graphical Abstract
Comparison of medical students' considerations in choosing a specialty: 2020 vs. 2009/10
Authors: Schroeder Hanna , Shacham Alon , Amar Shimon , Weissman Charles , Schroeder Josh E. 
Published: January 2024

Abstract
Background
Workforce shortage in healthcare and particularly in physicians poses a threat to healthcare delivery and its quality. In comparison to other OECD countries, Israel currently has a small number of medical graduates relative to its number of physicians, naturally emphasizing the importance of ensuring that this population chooses to remain in medicine. Understanding what is most important to medical students can help improve working conditions in residency. Such information is particularly needed to facilitate policy planning that will encourage the next generation of physicians to specialize in medical fields that are experiencing shortages. We hypothesized that between 2009/2010 and 2020, there were significant changes in medical students' preferences regarding their considerations for choosing a medical specialty.

Methods
We compared cross-sectional data from questionnaire-based surveys of 5th year medical students performed in 2009–2010 and 2020 at two Israeli universities.

Results
Of the 335 medical students who responded (237 and 98 in 2009/2010 and 2020, respectively) those in 2020 were 2.26 less likely vs. those in 2009/2010, to choose a residency for its high-paying potential (P < 0.05), and had significantly more interest in residencies with greater teaching opportunity (98.8% vs 82.9%, P < 0.05), increased responsibility and chances to make clinical decisions on their own (67.9% vs 51.6%, P < 0.05). Criteria important to both the 2009/2010 and 2020 students were choosing a bedside specialty (70.2%vs 67.9%, NS), and an interesting and challenging specialty (95.2%v s 91.3%, NS).

Conclusions
These results partially supported our hypothesis that medical students' preferences have changed over the years, though there are fundamental factors that apparently reflect medical students’ nature that do not change over time.
Central 5-HTergic hyperactivity induces myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-like pathophysiology
Authors: Lee Jin-Seok , Kang Ji-Yun , Park Samuel-Young , Hwang Seung-Ju , Bae Sung-Jin , Son Chang-Gue 
Published: January 2024

Abstract
Objectives
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a significant medical challenge, with no indisputable pathophysiological mechanism identified to date.

Methods
Based on clinical clues, we hypothesized that 5-hydroxytryptamine (5-HT) hyperactivation is implicated in the pathogenic causes of ME/CFS and the associated symptoms. We experimentally evaluated this hypothesis in a series of mouse models.

Results
High-dose selective serotonin reuptake inhibitor (SSRI) treatment induced intra- and extracellular serotonin spillover in the dorsal raphe nuclei of mice. This condition resulted in severe fatigue (rota-rod, fatigue rotating wheel and home-cage activity tests) and ME/CFS-associated symptoms (nest building, plantar and open field test), along with dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis response to exercise challenge. These ME/CFS-like features induced by excess serotonin were additionally verified using both a 5-HT synthesis inhibitor and viral vector for Htr1a (5-HT1A receptor) gene knockdown.

Conclusions
Our findings support the involvement of 5-HTergic hyperactivity in the pathophysiology of ME/CFS. This ME/CFS-mimicking animal model would be useful for understanding ME/CFS biology and its therapeutic approaches.
Single-cell transcriptome sequencing reveals aberrantly activated inter-tumor cell signaling pathways in the development of clear cell renal cell carcinoma
Authors: Zhang Junfeng , Liu Fuzhong , Guo Wenjia , Bi Xing , Yuan Shuai , Shayiti Fuerhaiti , Pan Ting , Li Kailing , Chen Peng 
Published: January 2024

Abstract
Background
Aberrant intracellular or intercellular signaling pathways are important mechanisms that contribute to the development and progression of cancer. However, the intercellular communication associated with the development of ccRCC is currently unknown. The purpose of this study was to examine the aberrant tumor cell-to-cell communication signals during the development of ccRCC.

Methods
We conducted an analysis on the scRNA-seq data of 6 ccRCC and 6 normal kidney tissues. This analysis included sub clustering, CNV analysis, single-cell trajectory analysis, cell–cell communication analysis, and transcription factor analysis. Moreover, we performed validation tests on clinical samples using multiplex immunofluorescence.

Results
This study identified eleven aberrantly activated intercellular signaling pathways in tumor clusters from ccRCC samples. Among these, two of the majors signaling molecules, MIF and SPP1, were mainly secreted by a subpopulation of cancer stem cells. This subpopulation demonstrated high expression levels of the cancer stem cell markers POU5F1 and CD44 (POU5F1hiCD44hiE.T), with the transcription factor POU5F1 regulating the expression of SPP1. Further research demonstrated that SPP1 binds to integrin receptors on the surface of target cells and promotes ccRCC development and progression by activating potential signaling mechanisms such as ILK and JAK/STAT.

Conclusion
Aberrantly activated tumor intercellular signaling pathways promote the development and progression of ccRCC. The cancer stem cell subpopulation (POU5F1hiCD44hiE.T) promotes malignant transformation and the development of a malignant phenotype by releasing aberrant signaling molecules and interacting with other tumor cells.
Bone marrow graft versus peripheral blood graft in haploidentical hematopoietic stem cells transplantation: a retrospective analysis in1344 patients of SFGM-TC registry
Authors: Lacan Claire , Lambert Jérôme , Forcade Edouard , Robin Marie , Chevallier Patrice , Loron Sandrine , Bulabois Claude-Éric , Orvain Corentin , Ceballos Patrice , Daguindau Etienne , Charbonnier Amandine , Chalandon Yves , Bernard Marc , Simand Célestine , Rubio Marie-Thérèse , Turlure Pascal , Maertens Johan , Huynh Anne , Loschi Michael , Bay Jacques-Olivier , Guillerm Gaëlle , Alani Mustafa , Castilla-Llorente Cristina , Poiré Xavier , Chantepie Sylvain , Maillard Natacha , Beguin Yves , Marçais Ambroise , Cornillon Jérôme , Malfuson Jean-Valère , Maury Sébastien , Meuleman Nathalie , Villate Alban , Bekadja Mohammed-Amine , Walter-Petrich Anouk , Jacque Nathalie , Srour Micha , Devillier Raynier , Nguyen Stéphanie 
Published: January 2024

AbstractThe use of peripheral blood (PB) or bone marrow (BM) stem cells graft in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remains controversial. Moreover, the value of adding anti-thymoglobulin (ATG) to PTCy is unknown. A total of 1344 adult patients received an unmanipulated haploidentical transplant at 37 centers from 2012 to 2019 for hematologic malignancy. We compared the outcomes of patients according to the type of graft, using a propensity score analysis. In total population, grade II–IV and III–IV acute GVHD (aGVHD) were lower with BM than with PB. Grade III–IV aGVHD was lower with BM than with PB + ATG. All outcomes were similar in PB and PB + ATG groups. Then, in total population, adding ATG does not benefit the procedure. In acute leukemia, myelodysplastic syndrome and myeloproliferative syndrome (AL-MDS-MPS) subgroup receiving non-myeloablative conditioning, risk of relapse was twice greater with BM than with PB (51 vs. 22%, respectively). Conversely, risk of aGVHD was greater with PB (38% for aGVHD II–IV; 16% for aGVHD III–IV) than with BM (28% for aGVHD II–IV; 8% for aGVHD III–IV). In this subgroup with intensified conditioning regimen, risk of relapse became similar with PB and BM but risk of aGVHD III–IV remained higher with PB than with BM graft (HR = 2.0; range [1.17–3.43], p = 0.012).