bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using machine learning to develop preoperative model for lymph node metastasis in patients with bladder urothelial carcinoma
Authors: Ji Junjie , Zhang Tianwei , Zhu Ling , Yao Yu , Mei Jingchang , Sun Lijiang , Zhang Guiming 
Published: June 2024

Abstract
Background
Lymph node metastasis (LNM) is associated with worse prognosis in bladder urothelial carcinoma (BUC) patients. This study aimed to develop and validate machine learning (ML) models to preoperatively predict LNM in BUC patients treated with radical cystectomy (RC).

Methods
We retrospectively collected demographic, pathological, imaging, and laboratory information of BUC patients who underwent RC and bilateral lymphadenectomy in our institution. Patients were randomly categorized into training set and testing set. Five ML algorithms were utilized to establish prediction models. The performance of each model was assessed by the area under the receiver operating characteristic curve (AUC) and accuracy. Finally, we calculated the corresponding variable coefficients based on the optimal model to reveal the contribution of each variable to LNM.

Results
A total of 524 and 131 BUC patients were finally enrolled into training set and testing set, respectively. We identified that the support vector machine (SVM) model had the best prediction ability with an AUC of 0.934 (95% confidence interval [CI]: 0.903–0.964) and accuracy of 0.916 in the training set, and an AUC of 0.855 (95%CI: 0.777–0.933) and accuracy of 0.809 in the testing set. The SVM model contained 14 predictors, and positive lymph node in imaging contributed the most to the prediction of LNM in BUC patients.

Conclusions
We developed and validated the ML models to preoperatively predict LNM in BUC patients treated with RC, and identified that the SVM model with 14 variables had the best performance and high levels of clinical applicability.
Air pollutants, seasonal influenza, and acute otitis media in children: a population-based analysis using 22-year hospitalization data
Authors: Li Conglu , Jiang Xiaoting , Wei Yuchen , Wang Yawen , Lao Xiangqian , Yue Qianying , Chong Ka Chun 
Published: June 2024

Abstract
Background
Acute otitis media (AOM) is a prevalent childhood acute illness, with 13.6 million pediatric office visits annually, often stemming from upper respiratory tract infections (URI) and affected by environmental factors like air pollution and cold seasons.

Methods
Herein, we made use of territory-wide hospitalization data to investigate the relationships between meteorological factors, air pollutants, influenza infection, and AOM for children observed from 1998 to 2019 in Hong Kong. Quasi-Poisson generalized additive model, combined with a distributed-lag non-linear model, was employed to examine the relationship between weekly AOM admissions in children and weekly influenza-like illness-positive (ILI +) rates, as well as air pollutants (i.e., oxidant gases, sulfur dioxide, and fine particulate matter), while accounting for meteorological variations.

Results
There were 21,224 hospital admissions due to AOM for children aged ≤ 15 years throughout a 22-year period. The cumulative adjusted relative risks (ARR) of AOM were 1.15 (95% CI, 1.04–1.28) and 1.07 (95% CI, 0.97–1.18) at the 95th percentile concentration of oxidant gases (65.9 ppm) and fine particulate matter (62.2 μg/m3) respectively, with reference set to their medians of concentration. The ARRs exhibited a monotone increasing trend for all-type and type-specific ILI + rates. Setting the reference to zero, the cumulative ARRs of AOM rose to 1.42 (95% CI, 1.29–1.56) at the 95th percentile of ILI + Total rate, and to 1.07 (95% CI, 1.01–1.14), 1.19 (95% CI, 1.11–1.27), and 1.22 (95% CI, 1.13–1.32) for ILI + A/H1N1, A/H3N2, and B, respectively.

Conclusions
Our findings suggested that policy on air pollution control and influenza vaccination for children need to be implemented, which might have significant implications for preventing AOM in children.
Effectiveness of home treatment in children and adolescents with psychiatric disorders—systematic review and meta-analysis
Authors: Graf Daniel , Sigrist Christine , Boege Isabel , Cavelti Marialuisa , Koenig Julian , Kaess Michael 
Published: June 2024

Abstract
Background
Home treatment in child and adolescent psychiatry offers an alternative to conventional inpatient treatment by involving the patient’s family, school, and peers more directly in therapy. Although several reviews have summarised existing home treatment programmes, evidence of their effectiveness remains limited and data synthesis is lacking.

Methods
We conducted a meta-analysis on the effectiveness of home treatment compared with inpatient treatment in child and adolescent psychiatry, based on a systematic search of four databases (PubMed, CINAHL, PsychINFO, Embase). Primary outcomes were psychosocial functioning and psychopathology. Additional outcomes included treatment satisfaction, duration, costs, and readmission rates. Group differences were expressed as standardised mean differences (SMD) in change scores. We used three-level random-effects meta-analysis and meta-regression and conducted both superiority and non-inferiority testing.

Results
We included 30 studies from 13 non-overlapping samples, providing data from 1795 individuals (mean age: 11.95 ± 2.33 years; 42.5% female). We found no significant differences between home and inpatient treatment for postline psychosocial functioning (SMD = 0.05 [− 0.18; 0.30], p = 0.68, I2 = 98.0%) and psychopathology (SMD = 0.10 [− 0.17; 0.37], p = 0.44, I2 = 98.3%). Similar results were observed from follow-up data and non-inferiority testing. Meta-regression showed better outcomes for patient groups with higher levels of psychopathology at baseline and favoured home treatment over inpatient treatment when only randomised controlled trials were considered.

Conclusions
This meta-analysis found no evidence that home treatment is less effective than conventional inpatient treatment, highlighting its potential as an effective alternative in child and adolescent psychiatry. The generalisability of these findings is reduced by limitations in the existing literature, and further research is needed to better understand which patients benefit most from home treatment.

Trial registration
Registered at PROSPERO (CRD42020177558), July 5, 2020.
DUSP5 regulated by YTHDF1-mediated m6A modification promotes epithelial-mesenchymal transition and EGFR-TKI resistance via the TGF-β/Smad signaling pathway in lung adenocarcinoma
Authors: Fan Weina , Xing Ying , Yan Shi , Liu Wei , Ning Jinfeng , Tian Fanglin , Wang Xin , Zhan Yuning , Luo Lixin , Cao Mengru , Huang Jian , Cai Li 
Published: June 2024

Abstract
Background
Lung adenocarcinoma (LUAD) patients have a dismal survival rate because of cancer metastasis and drug resistance. The study aims to identify the genes that concurrently modulate EMT, metastasis and EGFR-TKI resistance, and to investigate the underlying regulatory mechanisms.

Methods
Cox regression and Kaplan–Meier analyses were applied to identify prognostic oncogenes in LUAD. Gene set enrichment analysis (GSEA) was used to indicate the biological functions of the gene. Wound-healing and Transwell assays were used to detect migratory and invasive ability. EGFR-TKI sensitivity was evaluated by assessing the proliferation, clonogenic survival and metastatic capability of cancer cells with treatment with gefitinib. Methylated RNA immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP) analyses established the level of m6A modification present on the target gene and the protein’s capability to interact with RNA, respectively. Single-sample gene set enrichment (ssGSEA) algorithm used to investigate levels of immune cell infiltration.

Results
Our study identified dual-specificity phosphatase 5 (DUSP5) as a novel and powerful predictor of adverse outcomes for LUAD by using public datasets. Functional enrichment analysis found that DUSP5 was positively enriched in EMT and transforming growth factor-beta (TGF-β) signaling pathway, a prevailing pathway involved in the induction of EMT. As expected, DUSP5 knockdown suppressed EMT via inhibiting the canonical TGF-β/Smad signaling pathway in in vitro experiments. Consistently, knockdown of DUSP5 was first found to inhibit migratory ability and invasiveness of LUAD cells in in vitro and prevent lung metastasis in in vivo. DUSP5 knockdown re-sensitized gefitinib-resistant LUAD cells to gefitinib, accompanying reversion of EMT progress. In LUAD tissue samples, we found 14 cytosine-phosphate-guanine (CpG) sites of DUSP5 that were negatively associated with DUSP5 gene expression. Importantly, 5′Azacytidine (AZA), an FDA-approved DNA methyltransferase inhibitor, restored DUSP5 expression. Moreover, RIP experiments confirmed that YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), a m6A reader protein, could bind DUSP5 mRNA. YTHDF1 promoted DUSP5 expression and the malignant phenotype of LUAD cells. In addition, the DUSP5-derived genomic model revealed the two clusters with distinguishable immune features and tumor mutational burden (TMB).

Conclusions
Briefly, our study discovered DUSP5 which was regulated by epigenetic modification, might be a potential therapeutic target, especially in LUAD patients with acquired EGFR-TKI resistance.

Graphical Abstract
The modern-day “Rest Cure”: “The yellow Wallpaper” and underrepresentation in clinical research
Authors: Villar Camille Francesca 
Published: June 2024

AbstractGothic literature—a genre brimming with madness, supernaturalism, and psychological terror—offers innumerable case studies potentially representing how psychiatric patients perceive their treatment from healthcare professionals. Charlotte Perkins Gilman’s famous 1892 short story “The Yellow Wallpaper” offers a poignant example of this through its fictional narrator, a diarist many interpret to be suffering from postpartum depression. The fiction here does not stray far from reality: Gilman orchestrated her diarist’s experience to mirror her own, as both real author and fictional character suffocated from a melancholy only made worse by their physicians’ insistence on following the “Rest Cure.” While this instruction to cease all work and activity was a prevalent depression treatment at the time, Gilman, through “The Yellow Wallpaper,” reveals how the intervention ultimately harmed more than helped because it overlooked her—and, by extension, her fictional diarist’s— unique needs and identities. Today, while the ineffective Rest Cure no longer exists, applying observations from “The Yellow Wallpaper” to clinical research calls attention to underrepresentation in treatment development, a costly problem that could be mitigated by mindful incorporation of intersectionality theory into study designs.
Visualization of the existence of growth hormone secretagogue receptor in the rat nucleus accumbens
Authors: Lee Seohyeon , Cai Wen Ting , Yoon Hyung Shin , Kim Jeong-Hoon 
Published: June 2024

AbstractThe potential role of the ghrelin receptor, also known as the growth hormone secretagogue receptor (GHSR), within the nucleus accumbens (NAcc) in regulating drug addiction and feeding has been documented; however, the pattern of its expression in this site remains elusive. In this study, we characterized the expression patterns of GHSR1a and 1b, two subtypes of GHSRs, within the NAcc of the rat brain by immunohistochemistry. We visually detected GHSR signals, for the first time, at the protein level in the NAcc in which they were mostly expressed in neurons including both medium spiny neurons (MSNs) and non-MSNs. Furthermore, GHSR1a was found expressed as localized near the cellular membrane or some in the cytoplasm, whereas GHSR1b expressed solely throughout the large cytoplasmic area. The existence and subcellular expression pattern of GHSRs in the NAcc identified in this study will contribute to improving our understanding about the role of GHSR-mediated neurosignaling in feeding and drug addiction.
Leaf: an ultrafast filter for population-scale long-read SV detection
Authors: Pan Chenxu , Reinert Knut 
Published: June 2024

AbstractAdvances in sequencing technology have facilitated population-scale long-read structural variant (SV) detection. Arguably, one of the main challenges in population-scale analysis is developing effective computational pipelines. Here, we present a new filter-based pipeline for population-scale long-read SV detection. It better captures SV signals at an early stage than conventional assembly-based or alignment-based pipelines. Assessments in this work suggest that the filter-based pipeline helps better resolve intra-read rearrangements. Moreover, it is also more computationally efficient than conventional pipelines and thus may facilitate population-scale long-read applications.
Facilitators, barriers and support needs to GLA:D exercise adherence – a mixed method study
Authors: Matile Franziska , Nast Irina , Niedermann Karin 
Published: June 2024

Abstract
Background
Knee and hip osteoarthritis (OA) are among the most common musculoskeletal joint diseases worldwide. International guidelines recommend exercise and education as first-line interventions for their management. The Good Life with osteoArthritis Denmark (GLA:D) programme aims to achieve self-management using group exercise and education sessions. It also encourages participants to stay physically active and perform GLA:D exercises (GE) twice weekly after programme end. This study investigated the participants’ self-reported level of physical activity (PA) and self-reported adherence to the GE between five and 17 months after completion of the GLA:D programme and also explored the barriers, facilitators and support needs to achieve long-term adherence to GE.

Methods
A mixed method study using an exploratory sequential design was performed. A qualitative phase, involving semi-structured interviews and a focus group, led to the development of a questionnaire on participants’ level of PA, as well as ratings of the barriers, facilitators and support needs for the achievement of long-term adherence to GE. In a second quantitative phase, the survey was conducted online with former GLA:D participants from Switzerland. Descriptive statistical analysis and a group comparison between adherent and non-adherent participants to the GE were performed using Fisher’s exact test, odds ratio, and confidence interval.

Results
Eleven former GLA:D participants attended the interviews and focus group, and former GLA:D participants (30% response rate) participated in the survey. Of these, 84% (n = 285) reported to reach the recommended level of PA and 53% (n = 178) GE adherence. The top barrier to GE adherence was no/little self-discipline to perform GE (40%, n = 112) and the top facilitator was GE are easy to perform (93%, n = 300). The top 3 items regarding support needs to enhance GE adherence were a shortened version (max. 30 min) of the GE home programme (75%, n = 255), monthly continuation of small GE groups under GLA:D physiotherapists’ supervision (65%, n = 221), and monitoring with regular testing of individual progress (65%, n = 221).

Conclusions
The top barriers and facilitators should be considered by those responsible for the GLA:D programme and may need to be specifically addressed during and after the programme. The development of a shortened version of the GLA:D programme, a post-GLA:D group, and monitoring with regular testing seem crucial for enhancing GE adherence.

Clinical Trial Registration
not applicable.
A comprehensive analysis of m6A/m7G/m5C/m1A-related gene expression and immune infiltration in liver ischemia–reperfusion injury by integrating bioinformatics and machine learning algorithms
Authors: Meng Zhanzhi , Li Xinglong , Lu Shounan , Hua Yongliang , Yin Bing , Qian Baolin , Li Zhongyu , Zhou Yongzhi , Sergeeva Irina , Fu Yao , Ma Yong 
Published: June 2024

AbstractBackgroundLiver ischemia–reperfusion injury (LIRI) is closely associated with immune infiltration, which commonly occurs after liver surgery, especially liver transplantation. Therefore, it is crucial to identify the genes responsible for LIRI and develop effective therapeutic strategies that target immune response. Methylation modifications in mRNA play various crucial roles in different diseases. This study aimed to identify potential methylation-related markers in patients with LIRI and evaluate the corresponding immune infiltration.MethodsTwo Gene Expression Omnibus datasets containing human liver transplantation data (GSE12720 and GSE151648) were downloaded for integrated analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted to investigate the functional enrichment of differentially expressed genes (DEGs). Differentially expressed methylation-related genes (DEMRGs) were identified by overlapping DEG sets and 65 genes related toN6-methyladenosine (m6A), 7-methylguanine (m7G), 5-methylcytosine (m5C), andN1-methyladenosine (m1A). To evaluate the relationship between DEMRGs, a protein–protein interaction (PPI) network was utilized. The core DEMRGs were screened using three machine learning algorithms: least absolute shrinkage and selection operator, random forest, and support vector machine-recursive feature elimination. After verifying the diagnostic efficacy using the receiver operating characteristic curve, we validated the expression of the core DEMRGs in clinical samples and performed relative cell biology experiments. Additionally, the immune status of LIRI was comprehensively assessed using the single sample gene set enrichment analysis algorithm. The upstream microRNA and transcription factors of the core DEMRGs were also predicted.ResultsIn total, 2165 upregulated and 3191 downregulated DEGs were identified, mainly enriched in LIRI-related pathways. The intersection of DEGs and methylation-related genes yielded 28 DEMRGs, showing high interaction in the PPI network. Additionally, the core DEMRGsYTHDC1,METTL3,WTAP, andNUDT3demonstrated satisfactory diagnostic efficacy and significant differential expression and corresponding function based on cell biology experiments. Furthermore, immune infiltration analyses indicated that several immune cells correlated with all core DEMRGs in the LIRI process to varying extents.ConclusionsWe identified core DEMRGs (YTHDC1,METTL3,WTAP, andNUDT3) associated with immune infiltration in LIRI through bioinformatics and validated them experimentally. This study may provide potential methylation-related gene targets for LIRI immunotherapy.
Prebiotic galactooligosaccharide improves piglet growth performance and intestinal health associated with alterations of the hindgut microbiota during the peri-weaning period
Authors: Boston Timothy E. , Wang Feng , Lin Xi , Kim Sung Woo , Fellner Vivek , Scott Mark F. , Ziegler Amanda L. , Van Landeghem Laurianne , Blikslager Anthony T. , Odle Jack 
Published: June 2024

AbstractBackgroundWeaning stress reduces growth performance and health of young pigs due in part to an abrupt change in diets from highly digestible milk to fibrous plant-based feedstuffs. This study investigated whether dietary galactooligosaccharide (GOS), supplemented both pre- and post-weaning, could improve growth performance and intestinal health via alterations in the hindgut microbial community.MethodsUsing a 3 × 2 factorial design, during farrowing 288 piglets from 24 litters received either no creep feed (FC), creep without GOS (FG–) or creep with 5% GOS (FG+) followed by a phase 1 nursery diet without (NG–) or with 3.8% GOS (NG+). Pigs were sampled pre- (D22) and post-weaning (D31) to assess intestinal measures.ResultsCreep fed pigs grew 19% faster than controls (P < 0.01) prior to weaning, and by the end of the nursery phase (D58), pigs fed GOS pre-farrowing (FG+) were 1.85 kg heavier than controls (P < 0.05). Furthermore, pigs fed GOS in phase 1 of the nursery grew 34% faster (P < 0.04), with greater feed intake and efficiency. Cecal microbial communities clustered distinctly in pre- vs. post-weaned pigs, based on principal coordinate analysis (P < 0.01). No effects of GOS were detected pre-weaning, but gruel creep feeding increased Chao1 α-diversity and altered several genera in the cecal microbiota (P < 0.05). Post-weaning, GOS supplementation increased some genera such asFusicatenibacterandCollinsella,whereas others decreased such asCampylobacterandFrisingicoccus(P < 0.05). Changes were accompanied by higher molar proportions of butyrate in the cecum of GOS-fed pigs (P < 0.05).ConclusionsGruel creep feeding effectively improves suckling pig growth regardless of GOS treatment. When supplemented post-weaning, prebiotic GOS improves piglet growth performance associated with changes in hindgut microbial composition.
Hematological profiles and mortality risk in critically ill and drug-resistant tuberculosis patients: insights from a longitudinal study
Authors: Ali Asmaa , Wu Liang , Moazen Eman M. , Elsawy Sawsan Bakr , Salama Khadiga S. M. , Ullah Kalim , Elfeky Seham Ezzat Fathy , Alharbi Sami H. , Saleh Mai M. 
Published: June 2024

Abstract
Background
While tuberculosis (TB) remains a significant global health threat, data on mortality in critically ill TB patients and those with drug-resistant TB (DR-TB) is limited. This study explores hematological profiles of critically ill TB patients and those with DR-TB, investigating associations with in-hospital and short-term mortality.

Methods
A longitudinal study of 269 patients with confirmed TB evaluated baseline blood cell counts and indices from medical records. We calculated in-hospital mortality and short-term prognosis, followed by analysis to identify predictors of mortality using hematological parameters.

Results
One-third of TB patients were critically ill (35.32%) and required intensive care unit (ICU) admission, while 14.5% had DR-TB, more common in females and smokers. Critically ill patients were older and tended to be non-smokers. DR-TB patients exhibited elevated lymphocyte and monocyte counts but lower neutrophil count and blood indices. Critically ill DS-TB patients had lower hemoglobin (Hb) and platelet (PLT) but higher total leucocytes count (TLC) and mean platelet volume (MPV). In-hospital mortality rate was 29.37%, significantly higher in critically ill DS-TB patients (74.74%). In-hospital mortality was 14-fold higher in critically ill DS-TB patients, 11-fold higher in stable DR-TB patients, and 6-fold higher in patients with comorbidities. Decreased Hb, monocyte level, and neutrophil to lymphocyte ratio (NLR) were significantly associated with in-hospital mortality. Predictors of short-term mortality included critical illness and comorbidities. However, the effect of DR-TB on short-term mortality disappeared. Decreasing Hb and TLC, especially neutrophils were significantly linked to short-term mortality. The utility of Hb in discriminating in-hospital and short-term mortality was very good, with AUC values of 78% and 79%, respectively. Cutoff values of less than 10 mg/dL and 9.75 mg/dL showed sensitivity ranging from 71 to 80% and specificity ranging from 75 to 80%, respectively.

Conclusion
This study provides valuable insights into patients with DR-TB and DS-TB with critically illness. We observed elevated lymphocyte and monocyte counts in DR-TB patients, as well as significant alterations in blood indices in critically ill patients. Importantly, the in-hospital mortality was notably higher in critically ill DS-TB patients, highlighting the importance of early recognition and aggressive management in this subgroup. Specifically, certain blood parameters such as hemoglobin, monocytes, neutrophils, and the NLR were associated with an increased risk of both in-hospital and short-term mortality. Furthermore, our findings underscore the prognostic significance of hematological parameters, particularly in resource-limited settings.