bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new variant in theZCCHC8gene: diverse clinical phenotypes and expression in the lung
Authors: Groen Karlijn , van der Vis Joanne J. , van Batenburg Aernoud A. , Kazemier Karin M. , de Bruijn Marjolein J.W. , Stadhouders Ralph , Arp Pascal , Verkerk Annemieke J.M.H. , Schoemaker Angela E. , de Bie Charlotte I. , Massink Maarten P.G. , van Beek Frouke T. , Grutters Jan C. , Vergouw Leonie J.M. , van Moorsel Coline H.M. 
Published: November 2023

IntroductionPulmonary fibrosis is a severe disease which can be familial. A genetic cause can only be found in ∼40% of families. Searching for shared novel genetic variants may aid the discovery of new genetic causes of disease.MethodsWhole-exome sequencing was performed in 152 unrelated patients with a suspected genetic cause of pulmonary fibrosis from the St Antonius interstitial lung disease biobank. Variants of interest were selected by filtering for novel, potentially deleterious variants that were present in at least three unrelated pulmonary fibrosis patients.ResultsThe novel c.586G>A p.(E196K) variant in theZCCHC8gene was observed in three unrelated patients: two familial patients and one sporadic patient, who was later genealogically linked to one of the families. The variant was identified in nine additional relatives with pulmonary fibrosis and other telomere-related phenotypes, such as pulmonary arterial venous malformations, emphysema, myelodysplastic syndrome, acute myeloid leukaemia and dyskeratosis congenita. One family showed incomplete segregation, with absence of the variant in one pulmonary fibrosis patient who carried aPARNvariant. The majority ofZCCHC8variant carriers showed short telomeres in blood. ZCCHC8 protein was located in different lung cell types, including alveolar type 2 (AT2) pneumocytes, the culprit cells in pulmonary fibrosis. AT2 cells showed telomere shortening and increased DNA damage, which was comparable to patients with sporadic pulmonary fibrosis and those with pulmonary fibrosis carrying a telomere-related gene variant, respectively.DiscussionTheZCCHC8c.586G>A variant confirms the involvement of ZCCHC8 in pulmonary fibrosis and short-telomere syndromes and underlines the importance of including theZCCHC8gene in diagnostic gene panels for these diseases.
Melatonin or its analogs as premedication to prevent emergence agitation in children: a systematic review and meta-analysis
Authors: Zhang Dongni , Jia Xiaotong , Lin Duomao , Ma Jun 
Published: November 2023

Abstract
Background
Emergence agitation (EA) is a prevalent complication in children following general anesthesia. Several studies have assessed the relationship between melatonin or its analogs and the incidence of pediatric EA, yielding conflicting results. This meta-analysis aims to assess the effects of premedication with melatonin or its analogs on preventing EA in children after general anesthesia.

Methods
PubMed, EMBASE, the Cochrane Library, ProQuest Dissertations & Theses Global, Web of Science, CNKI, Wanfang Data, clinicaltrials.gov, and WHO International Clinical Trials Registry Platform were searched until 25 November 2022. We included randomized controlled trials that assessed EA in patients less than 18 years old who underwent general anesthesia. We excluded studies that did not use a specific evaluation to assess EA.

Results
Nine studies (951 participants) were included in this systematic review. Melatonin significantly reduced the incidence of EA compared with placebos (risk ratio 0.40, 95% CI 0.26 to 0.61, P < 0.01) and midazolam (risk ratio 0.48, 95% CI 0.32 to 0.73, P < 0.01). Dexmedetomidine remarkably decreased the incidence of EA compared with melatonin (risk ratio 2.04, 95% CI 1.11 to 3.73, P = 0.02).

Conclusions
Melatonin premedication significantly decreases the incidence of EA compared with placebos and midazolam. Dexmedetomidine premedication has a stronger effect than melatonin in preventing EA. Nevertheless, further studies are warranted to reinforce and validate the conclusion on the efficacy of melatonin premedication in mitigating EA in pediatric patients.
Long-term psychological outcomes following stroke: the OX-CHRONIC study
Authors: Kusec Andrea , Milosevich Elise , Williams Owen A. , Chiu Evangeline G. , Watson Pippa , Carrick Chloe , Drozdowska Bogna A. , Dillon Avril , Jennings Trevor , Anderson Bloo , Dawes Helen , Thomas Shirley , Kuppuswamy Annapoorna , Pendlebury Sarah T. , Quinn Terence J. , Demeyere Nele 
Published: November 2023

Abstract
Background
Stroke survivors rate longer-term (> 2 years) psychological recovery as their top priority, but data on how frequently psychological consequences occur is lacking. Prevalence of cognitive impairment, depression/anxiety, fatigue, apathy and related psychological outcomes, and whether rates are stable in long-term stroke, is unknown.

Methods
N = 105 long-term stroke survivors (M [SD] age = 72.92 [13.01]; M [SD] acute NIH Stroke Severity Score = 7.39 [6.25]; 59.0% Male; M [SD] years post-stroke = 4.57 [2.12]) were recruited (potential N = 208). Participants completed 3 remote assessments, including a comprehensive set of standardized cognitive neuropsychological tests comprising domains of memory, attention, language, and executive function, and questionnaires on emotional distress, fatigue, apathy and other psychological outcomes. Ninety participants were re-assessed one year later. Stability of outcomes was assessed by Cohen’s d effect size estimates and percent Minimal Clinically Important Difference changes between time points.

Results
On the Montreal Cognitive Assessment 65.3% scored < 26. On the Oxford Cognitive Screen 45.9% had at least one cognitive impairment. Attention (27.1%) and executive function (40%) were most frequently impaired. 23.5% and 22.5% had elevated depression/anxiety respectively. Fatigue (51.4%) and apathy (40.5%) rates remained high, comparable to estimates in the first-year post-stroke. Attention (d = -0.12; 85.8% stable) and depression (d = 0.09, 77.1% stable) were the most stable outcomes. Following alpha-adjustments, only perceptuomotor abilities (d = 0.69; 40.4% decline) and fatigue (d = -0.33; 45.3% decline) worsened over one year. Cognitive impairment, depression/anxiety, fatigue and apathy all correlated with worse quality of life.

Conclusion
Nearly half of participants > 2 years post-event exhibited psychological difficulties including domains of cognition, mood, and fatigue, which impact long-term quality of life. Stroke is a chronic condition with highly prevalent psychological needs, which require monitoring and intervention development.
Efficacy and safety of PD-1 inhibitors in recurrent or metastatic nasopharyngeal carcinoma patients after failure of platinum-containing regimens: a systematic review and meta-analysis
Authors: Luo Jian , Xiao Wanying , Hua Fengyang , Cao Yanqing , Wang Dongxia , Wang Xicheng 
Published: November 2023

Abstract
Objective
There is a lack of standard salvage treatment options for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) that has failed platinum-containing regimens. Breakthroughs in immunotherapy have opened up new options for these patients. However, the efficacy and safety of immunotherapy have not been clarified. This study aimed to summarize and assess the efficacy and safety of PD-1 inhibitors in patients with RM-NPC who failed platinum-containing chemotherapy.

Methods
Up to August 25, 2022, clinical trials of PD-1 inhibitors in RM-NPC patients who failed platinum-containing regimens were searched in the PubMed, Embase, Cochrane, and Web of Science databases. Retrieval subject terms included “nasopharyngeal carcinoma”, “metastatic”, “recurrence”, “PD-1”, and “PD-L1”. The clinical trials eligible for inclusion were systematically reviewed and meta-analyzed.

Results
A total of 9 studies including 842 patients with RM-NPC were included in this meta-analysis. The results showed that PD-1 inhibitors had promising efficacy in patients with RM-NPC who failed platinum-containing regimens: objective response rate (ORR) was 24% (95% confidence interval [CI] 21–26%), disease control rate (DCR) was 52% (95% CI 45–58%), 1-year progression-free survival (PFS) rate was 25% (95% CI 18–32%), and 1-year overall survival (OS) rate was 53% (95% CI 37–68%). In terms of treatment-related adverse events (AEs), the incidence of grade ≥ 3 treatment-related AEs was 19% (95% CI 13–24%). In addition, we found that PD-1 inhibitors were more effective in patients with PD-L1 positive than in patients with PD-L1 negative nasopharyngeal carcinoma who had failed platinum-containing regimens (ORR 31% (95%CI 26–35%) vs. 21% (95% CI 17–25%)).

Conclusion
PD-1 inhibitors may provide a survival benefit for patients with RM-NPC who have failed platinum-containing regimens and have the advantage of a good safety profile, making them a promising treatment option.
Discharge to home from a palliative care unit: impact on survival and factors associated with home death after the discharge: a cohort study
Authors: Murakami Nozomu , Kajiura Shinya , Tanabe Kouichi , Tsukada Kenichiro , Shibata Kazuhiko , Minabe Yoshio , Morita Tatsuya , Hayashi Ryuji 
Published: November 2023

Abstract
Background
Staying at home during the dying process is important for many patients; and palliative care units (PCUs) can help facilitate home death. This study compared patient survival between those who were discharged to home from a palliative care unit and those who were not, and aimed to identify the factors associated with home death after the discharge.

Methods
This retrospective cohort study used a database of patients admitted to a palliative care unit at Kouseiren Takaoka Hospital in Japan. All consecutive patients admitted to the hospital’s PCU between October 2016 and March 2020 were enrolled. Patient survival and factors potentially associated with survival and place of death were obtained. A total of 443 patients with cancer were analyzed, and 167 patients were discharged to home and 276 were not.

Results
Propensity score matching analyses revealed that median survival time was significantly longer in patients who were discharged to home than those who were not (57 vs. 27 days, P < 0.001). Multiple logistic regression analysis identified that worse Palliative Prognostic Index (odds ratio [OR] = 1.21, 95% confidence interval [CI] = 1.03–1.44, p = 0.025) and family members’ desire for home death (OR = 6.30, 95% CI = 2.32–17.1, p < 0.001) were significantly associated with home death after their discharge.

Conclusions
Discharge to home from palliative care units might have some positive impacts on patient survival.
Use of machine learning to assess factors affecting progression, retention, and graduation in first-year health professions students in Qatar: a longitudinal study
Authors: Hammoudi Halat Dalal , Abdel-Salam Abdel-Salam G. , Bensaid Ahmed , Soltani Abderrezzaq , Alsarraj Lama , Dalli Roua , Malki Ahmed 
Published: November 2023

Abstract
Background
Across higher education, student retention, progression, and graduation are considered essential elements of students’ academic success. However, there is scarce literature analyzing these attributes across health professions education. The current study aims to explore rates of student retention, progression, and graduation across five colleges of the Health Cluster at Qatar University, and identify predictive factors.

Methods
Secondary longitudinal data for students enrolled at the Health Cluster between 2015 and 2021 were subject to descriptive statistics to obtain retention, progression and graduation rates. The importance of student demographic and academic variables in predicting retention, progression, or graduation was determined by a predictive model using XGBoost, after preparation and feature engineering. A predictive model was constructed, in which weak decision tree models were combined to capture the relationships between the initial predictors and student outcomes. A feature importance score for each predictor was estimated; features that had higher scores were indicative of higher influence on student retention, progression, or graduation.

Results
A total of 88% of the studied cohorts were female Qatari students. The rates of retention and progression across the studied period showed variable distribution, and the majority of students graduated from health colleges within a timeframe of 4–7 years. The first academic year performance, followed by high school GPA, were factors that respectively ranked first and second in importance in predicting retention, progression, and graduation of health majors students. The health college ranked third in importance affecting retention and graduation and fifth regarding progression. The remaining factors including nationality, gender, and whether students were enrolled in a common first year experience for all colleges, had lower predictive importance.

Conclusions
Student retention, progression, and graduation at Qatar University Health Cluster is complex and multifactorial. First year performance and secondary education before college are important in predicting progress in health majors after the first year of university study. Efforts to increase retention, progression, and graduation rates should include academic advising, student support, engagement and communication. Machine learning-based predictive algorithms remain a useful tool that can be precisely leveraged to identify key variables affecting health professions students’ performance.
Attributing practice variation by its sources: the case of varicose veins treatments in the Netherlands
Authors: Schippa Luca , Gaspar Katalin , van der Hijden Eric , Koolman Xander 
Published: November 2023

Abstract
Background
Unwarranted practice variation refers to regional differences in treatments that are not driven by patients’ medical needs or preferences. Although it is the subject of numerous studies, most research focuses on variation at the end stage of treatment, i.e. the stage of the treating specialist, disregarding variation stemming from other sources (e.g. patient preferences, general practitioner referral patterns). In the present paper, we introduce a method that allows us to measure regional variation at different stages of the patient journey leading up to treatment.

Methods
A series of logit regressions estimating the probability of (1) initial visit with the physician and (2) treatment correcting for patient needs and patient preferences. Calculating the coefficient of variation (CVU) at each stage of the patient journey.

Results
Our findings show large regional variations in the probability of receiving an initial visit, The CVU, or the measure of dispersion, in the regional probability of an initial visit with a specialist was significantly larger (0.87–0.96) than at the point of treatment both conditional (0.14–0.25) and unconditional on an initial visit (0.65–0.74), suggesting that practice variation was present before the patient reached the specialist.

Conclusions
We present a new approach to attribute practice variation to different stages in the patient journey. We demonstrate our method using the clinically-relevant segment of varicose veins treatments. Our findings demonstrate that irrespective of the gatekeeping role of general practitioners (GPs), a large share of practice variation in the treatment of varicose veins is attributable to regional variation in primary care referrals. Contrary to expectation, specialists’ decisions meaningfully diminish rather than increase the amount of regional variation.
The contribution of Coriandrum sativum in enhancing Oreochromis niloticus rearing at sub-optimal temperatures: effect on growth, health status, survival rate, and resistance to Aeromons Veronii
Authors: Said Ahmed Abdou , Reda Rasha M. , Metwally Mohamed M. M. , El-Hady Heba M. Abd 
Published: November 2023

AbstractThis study (60 days) was conducted to investigate the ability of diet enriched with Coriandrum sativum powder or its extract to protect Oreochromis niloticus health and survivability at suboptimal temperature (21 ℃). One hundred and twenty (33.14 ± 0.5 g) were divided into four groups; each group has three replicates.. The first control group fed on a basal diet. Second and third groups fed on diet enriched with 30 mg/kg coriander seed powder (CP) and coriander seed ethanolic extract (CE), respectively. The fourth group (OT) fed on diet enriched with 500 mg oxytetracycline/kg diet. The results revealed that CE exhibited a considerable improvement in hematological parameters, hepatic-renal functions, antioxidant status, and immunological markers as well as remarkably increased resistance against Aeromonas veronii. It could be concluded that feeding tilapia CE enriched diet at 30 mg/kg is a recommended strategy to enhance tilapia health and resistance to A. veronii infection reared at 21 ℃.
Progranulin and GPNMB: interactions in endo-lysosome function and inflammation in neurodegenerative disease
Authors: Gillett Drew A. , Wallings Rebecca L. , Uriarte Huarte Oihane , Tansey Malú Gámez 
Published: November 2023

Abstract
Background
Alterations in progranulin (PGRN) expression are associated with multiple neurodegenerative diseases (NDs), including frontotemporal dementia (FTD), Alzheimer’s disease (AD), Parkinson’s disease (PD), and lysosomal storage disorders (LSDs). Recently, the loss of PGRN was shown to result in endo-lysosomal system dysfunction and an age-dependent increase in the expression of another protein associated with NDs, glycoprotein non-metastatic B (GPNMB).

Main body
It is unclear what role GPNMB plays in the context of PGRN insufficiency and how they interact and contribute to the development or progression of NDs. This review focuses on the interplay between these two critical proteins within the context of endo-lysosomal health, immune function, and inflammation in their contribution to NDs.

Short conclusion
PGRN and GPNMB are interrelated proteins that regulate disease-relevant processes and may have value as therapeutic targets to delay disease progression or extend therapeutic windows.
Alfalfa vein mottling virus, a novel potyvirid infecting Medicago sativa L.
Authors: Nemchinov Lev G. , Postnikova Olga A. , Wintermantel William M. , Palumbo John C. , Grinstead Sam 
Published: November 2023

Abstract
Background
We have recently identified a novel virus detected in alfalfa seed material. The virus was tentatively named alfalfa-associated potyvirus 1, as its genomic fragments bore similarities with potyvirids. In this study, we continued investigating this novel species, expanding information on its genomic features and biological characteristics.

Methods
This research used a wide range of methodology to achieve end results: high throughput sequencing, bioinformatics tools, reverse transcription-polymerase chain reactions, differential diagnostics using indicator plants, virus purification, transmission electron microscopy, and others.

Results
In this study, we obtained a complete genome sequence of the virus and classified it as a tentative species in the new genus, most closely related to the members of the genus Ipomovirus in the family Potyviridae. This assumption is based on the genome sequence and structure, phylogenetic relationships, and transmission electron microscopy investigations. We also demonstrated its mechanical transmission to the indicator plant Nicotiana benthamiana and to the natural host Medicago sativa, both of which developed characteristic symptoms therefore suggesting a pathogenic nature of the disease.

Conclusions
Consistent with symptomatology, the virus was renamed to alfalfa vein mottling virus. A name Alvemovirus was proposed for the new genus in the family Potyviridae, of which alfalfa vein mottling virus is a tentative member.
HLA-DR genetic polymorphisms and hepatitis B virus mutations affect the risk of hepatocellular carcinoma in Han Chinese population
Authors: Zhao Yubao , Chen Kun , Yang Hui , Zhang Feng , Ding Lu , Liu Yan , Zhang Le , Zhang Yuchen , Wang Huiliang , Deng Yang 
Published: November 2023

Abstract
Background
Human leucocyte antigen (HLA)-DR plays a crucial role in the immune response against hepatitis B virus (HBV). We aimed to investigate the associations of HLA-DR single nucleotide polymorphisms (SNPs) with the generation of hepatocellular carcinoma (HCC)-related HBV mutations. The effects of HLA-DR SNPs and their interactions with HBV mutations on HCC risks were also determined.

Methods
Five HLA-DR SNPs (rs3135363, rs9268644, rs35445101, rs24755213, and rs984778) were genotyped in 792 healthy controls, 586 chronic hepatitis B (CHB) patients, 536 liver cirrhosis (LC) patients, and 1500 HCC patients using quantitative PCR. Sanger sequencing was used to identify the HBV mutations. Logistic regression model was performed to evaluate the association of HLA-DR SNPs with HCC risk and the frequencies of HCC-related HBV mutations.

Results
The variant genotypes at rs3135363, rs9268644, rs35445101, rs24755213, and rs984778 were associated with decreased HCC risks. In genotype C HBV-infected subjects, variant genotypes of these SNPs were associated with decreased frequencies of HCC-related HBV mutations such as C1653T, T1674C/G, G1719T, T1753A/C, A1762T/G1764A, A1846T, G1896A, G1899A, and preS deletion. AG genotype at rs3135363, CA genotype at rs9268644, and AG genotype at rs24755213 reduced the generation of T1753A/C and G1896A in genotype B HBV-infected subjects, respectively. In addition, the interactions of rs3135363, rs9268644, rs24755213 with C1653T, T1753A/C, A1846T, and G1896A decreased the risks of HCC.

Conclusions
HLA-DR genetic polymorphisms might predispose the host to immunoselection of HCC-related HBV mutations and affect the HCC risks possibly through interacting with HBV mutations.
Adipose-derived exosomal miR-421 targets CBX7 and promotes metastatic potential in ovarian cancer cells
Authors: Zhang Yi , Tedja Roslyn , Millman Michael , Wong Terrence , Fox Alexandra , Chehade Hussein , Gershater Meyer , Adzibolosu Nicholas , Gogoi Radhika , Anderson Matthew , Rutherford Thomas , Zhang Zhenggang , Chopp Michael , Mor Gil , Alvero Ayesha B. 
Published: November 2023

Abstract
Background
Chromobox protein homolog 7 (CBX7), a member of the Polycomb repressor complex, is a potent epigenetic regulator and gene silencer. Our group has previously reported that CBX7 functions as a tumor suppressor in ovarian cancer cells and its loss accelerated formation of carcinomatosis and drove tumor progression in an ovarian cancer mouse model. The goal of this study is to identify specific signaling pathways in the ovarian tumor microenvironment that down-regulate CBX7. Given that adipocytes are an integral component of the peritoneal cavity and the ovarian tumor microenvironment, we hypothesize that the adipose microenvironment is an important regulator of CBX7 expression.

Results
Using conditioned media from human omental explants, we found that adipose-derived exosomes mediate CBX7 downregulation and enhance migratory potential of human ovarian cancer cells. Further, we identified adipose-derived exosomal miR-421 as a novel regulator of CBX7 expression and the main effector that downregulates CBX7.

Conclusion
In this study, we identified miR-421 as a specific signaling pathway in the ovarian tumor microenvironment that can downregulate CBX7 to induce epigenetic change in OC cells, which can drive disease progression. These findings suggest that targeting exosomal miR-421 may curtail ovarian cancer progression.