bluuebunny/crossref_metadata_2025 huggingface dataset:
School and student characteristics related to primary and secondary school students’ social–emotional functioning
Authors: de Bruijn Anne G. M. , Ehren Melanie C. M. , Meeter Martijn , Kortekaas-Rijlaarsdam Anne Fleur
Published: February 2025

Introduction

A healthy social–emotional functioning is vital for students’ general development and wellbeing. The school environment is a major determinant of social–emotional functioning, yet little is known about school-level and student-level characteristics related to healthy social–emotional functioning. In this study, we examined school-level characteristics (school size, school disadvantage score, urbanization level, and school denomination) and student-level characteristics (grade, secondary school track, participation in a COVID-19-related catch-up program, and measurement moment - during or after COVID-19) as predictors of students’ motivation for school, academic self-concept, social acceptance, and school wellbeing.

Methods

In school year 2020–2021, just after the first Covid-19 outbreak, 3,764 parents of primary school students from 242 Dutch primary schools and 2,545 secondary school students from 62 secondary schools filled out online questionnaires, before and after a Covid-19 related catch-up program was implemented at their school. Reliable and validated questionnaires were used to assess students’ motivation (Intrinsic Motivation Inventory), academic self-concept (Harter Self Perception Profile for Children; Self-Description Questionnaire-II), school wellbeing (Dutch School Questionnaire) and social acceptance (PRIMA Social Acceptance Questionnaire). School characteristics were derived from online databases. Student participation in a catch-up program and measurement moment (before or after the program) were taken into account. Data was analyzed via multilevel General Linear Mixed Models, separately for primary and secondary education.

Results

Of the school-level factors, only school disadvantage score was a significant predictor, specifically for primary school students’ motivation. Of the student-level characteristics, grade and catch-up participation were significant predictors of lower motivation, academic self-concept and school-wellbeing in primary school. In secondary school, students in higher grades had significantly lower motivation and school wellbeing; participants in catch-up program had a significantly lower academic self-concept; and perceived social-acceptance and school wellbeing were significantly lower just after COVID-19.

Conclusion

School-level characteristics only played a minor role in explaining differences in students’ social–emotional functioning. In both primary and secondary education, students in higher grades and participating in catch-up programs scored lower on their social–emotional functioning. Schools should be aware of students in higher grades being at risk for more problems in their social–emotional functioning.
Calculating maternal polygenic risk scores from prenatal screening by cell-free DNA data
Authors: Corey Victoria , Chavez Mauro , Qasim Layla , Dincer Tevfik U. , Henry Angela , Bagayan Salome , Treadup Sasha , Mehan Mike , de Feo Eileen , Kim Sung
Published: February 2025

Polygenic Risk Scores (PRS) have enabled quantification of genetic risk for many common and complex traits. Here we developed a novel method to estimate maternal PRS using low-coverage whole genome sequencing data from prenatal screening by cell-free DNA data intended to screen for fetal chromosomal aneuploidies. A prospective study was conducted where 455 consented patients that performed prenatal screening by cell-free DNA as part of their standard of care were randomly selected. Cell-free DNA and genomic DNA were isolated from the plasma and buffy coat of the blood drawn from pregnant women, respectively. Cell-free DNA was sequenced at ∼0.25x coverage while genomic DNA was sequenced at ∼15x coverage. The sequence data was used to impute genotypes which were then used to calculate PRS for paired comparisons. There was a high correlation (average = ∼0.9 across different PRS panels and panel sizes) between PRS from prenatal screening by cfDNA data and PRS from genome sequence data of the buffy coat. This proof-of-concept study illustrates that maternal PRS can be calculated using low-coverage prenatal screening by cfDNA sequence data with high accuracy.
Deciphering the role of CNIH4 in pan-cancer landscapes and its significance in breast cancer progression
Authors: Xu Yao , Lai Zengzhen , Li Chaolin
Published: February 2025

Background

The escalating global cancer burden necessitates the development of biomarkers with enhanced specificity and sensitivity for early diagnosis and therapeutic efficacy monitoring. The CNIH4 gene, an emerging biomarker, is increasingly recognized for its role in the malignant progression across various cancers.

Methods

We conducted a comprehensive multi-omics analysis of CNIH4, including pan-cancer expression profiles, epigenetic alterations, immune microenvironment characteristics, and therapeutic response patterns. Our focus was on clinical features, molecular underpinnings, and drug sensitivity in breast cancer (BRCA) associated with CNIH4. In vitro studies were also performed to assess the effects of CNIH4 knockdown on cell proliferation and cell cycle in the MDA-MB-231 cell line.

Results

CNIH4 upregulation was observed in multiple cancers, significantly correlating with genomic instability. High CNIH4 expression levels were linked to poor prognosis across cancers and associated with key cancer-related pathways, particularly those in cell cycle regulation and DNA repair. Correlation analyses suggest a role for CNIH4 in the tumor immune microenvironment, as evidenced by its association with immune subtypes, immune-related genes, and immune cell infiltration. Single-cell and spatial transcriptome analyses confirmed that CNIH4 expression in BRCA predicts tumor malignancy. Drug sensitivity analysis revealed a significant correlation between CNIH4 and responsiveness to various kinase inhibitors and chemotherapeutic agents. In vitro experiments demonstrated that CNIH4 knockdown significantly impacts the proliferation and cell cycle of MDA-MB-231 cells.

Conclusion

Our study highlights CNIH4 as a promising pan-cancer biomarker with significant implications for tumor progression and a critical role in cell cycle regulation in BRCA.
Correlation and clinical significance of GSTP1 hypermethylation in hepatocellular carcinoma: a systematic review and meta-analysis
Authors: Li Pengfei , He Lei , Zhang Chunxia , Huang Xinyao , Sun Rong , Zhang Yan , Wang Yan
Published: February 2025

Background

Hepatocellular carcinoma (HCC) is one of the most prevalent and fatal cancers globally, with poor prognosis due to late-stage diagnosis and limited early detection methods. GSTP1 gene hypermethylation has been implicated in various cancers, including HCC, as a potential biomarker for diagnosis, prognosis, and therapeutic strategies. This systematic review and meta-analysis aimed to assess the association between GSTP1 hypermethylation and HCC, and its clinical significance.

Methods

A comprehensive literature search was conducted across PubMed, Embase, Web of Science, and the Cochrane Library to identify studies examining GSTP1 hypermethylation in HCC. Studies included in the meta-analysis were observational (case-control, cohort) or experimental studies (clinical trials) that reported on the correlation between GSTP1 hypermethylation and clinical outcomes in HCC patients. Pooled odds ratios (ORs) and weighted mean differences (WMDs) were calculated using random or fixed-effects models based on heterogeneity.

Results

A total of 10 case-control studies were included, comprising 1,133 participants. The analysis revealed a significant association between GSTP1 hypermethylation and the presence of HCC (OR = 6.64, 95% CI: 2.17–20.38). GSTP1 hypermethylation was more frequently observed in liver cancer tissue compared to liver tissue from patients with other diseases (P < 0.00001). Additionally, a significant correlation between GSTP1 hypermethylation and poor clinical outcomes, such as advanced tumor stage, recurrence, and reduced overall survival, was observed (OR = 2.56, 95% CI: 1.80–3.64). Subgroup analyses based on study design, sample type, and detection method showed no significant heterogeneity in most comparisons.

Conclusion

GSTP1 hypermethylation is significantly associated with the presence of HCC and poorer clinical outcomes, making it a promising biomarker for early diagnosis and prognosis. These findings highlight the potential for GSTP1 methylation as a diagnostic and prognostic tool in HCC management. Further large-scale, multicenter studies are required to standardize detection methods and evaluate the therapeutic potential of epigenetic reactivation of GSTP1 in HCC patients.
Short-term fasting before living kidney donation has an immune-modulatory effect
Authors: Oudmaijer Christiaan A. J. , Komninos Daphne S. J. , Ozinga Rutger A. , Smit Kimberly , Rozendaal Nina E. M. , Hoeijmakers Jan H. J. , Vermeij Wilbert P. , Aerts Joachim G. J. V. , IJzermans Jan N. M. , Willemsen Marcella
Published: February 2025

Background

Short-Term Fasting (STF) is an intervention reducing the intake of calories, without causing undernutrition or micronutrient-related malnutrition. It aims to systemically improve resilience against acute stress. Several (pre-)clinical studies have suggested protective effects of STF, marking the systemic effects STF can induce in respect to surgery and ischemia-reperfusion injury. In addition, STF also affects the number of circulating immune cells. We aim to determine the effect of STF on the abundance and phenotype of different immune cell populations.

Methods

Thirty participants were randomly selected from the FAST clinical trial, including living kidney donors, randomized to an STF-diet or control arm. In an observational cohort sub-study we prospectively included 30 patients who donated blood samples repeatedly during study runtime. Using flow cytometry analyses, immune cell phenotyping was performed on peripheral blood mononuclear cells. Three panels were designed to investigate the presence and activation status of peripheral T cells, B cells, dendritic cells (DCs) and myeloid cells.

Results

Eight participants were excluded due to sample constraints. Baseline characteristics showed no significant differences, except for fasting duration. Weight changes were minimal and non-significant across different time intervals, with slight trends toward long-term weight loss pre-surgery. Glucose, insulin, and β-hydroxybutyrate levels differed significantly between groups, reflecting adherence to the fasting diet. Flow cytometry and RNA sequencing analysis revealed no baseline differences between groups, with high variability within each group. STF changes the levels and phenotype of immune cells, reducing the abundance and activation of T cells, including regulatory T cells, increased presence of (naïve) B cells, and elevation of type 1 conventional DCs (cDC1s). In addition, a decrease in central memory T cells was observed.

Discussion

In this study, we observed significant changes due to fasting in B cells, T cells, and DCs, specifically toward less specialized lymphocytes, suggesting an arrest in B and T cell development. Further research should focus on the clinical implications of changes in immune cells and significance of these observed immunological changes.

Conclusion

STF results in reduced numbers and activation status of T cells and Tregs, increased presence of (naïve) B cells, and elevation of cDC1s.
Modeling human natural killer cell development and drug response in a microfluidic bone marrow model
Authors: Koenig Leopold , Ben-Eliezer Inbal , Tao Thi Phuong , Winter Annika , Grossman Moran
Published: February 2025

Introduction

The human bone marrow is a complex organ that is critical for self-renewal and differentiation of hematopoietic progenitor cells into various lineages of blood cells. Perturbations of the hematopoietic system have been reported to cause numerous diseases. Yet, understanding the fundamental biology of the human bone marrow in health and disease and during the preclinical stages of drug development is challenging due to the complexity of studying or manipulating the human bone marrow. Human cell-based microfluidic bone marrow models are promising research tools to explore multi-lineage differentiation of human stem and progenitor cells over long periods of time.

Methods

Human hematopoietic stem and progenitor cells were cultured with mesenchymal stromal cells on a zirconium oxide ceramic scaffold in a microfluidic device recapitulating the human bone marrow. NK cell differentiation was induced by the application of a lymphoid cultivation medium containing IL-15. The kinetics of differentiation into mature NK cells was traced by flow cytometry over a period of up to seven weeks, and functionality was measured by stimulation with phorbol myristate acetate (PMA) and ionomycin. The effect of an anti-IL-15 monoclonal antibody (TEV-53408) on different NK cell subtypes was tested at different time points.

Results

Our data shows that within 28 days of culture, differentiation into all developmental stages of NK cells was accomplished in this system. Alongside with the NK cells, myeloid cells developed in the system including granulocytes, monocytes and dendritic cells. The differentiated NK cells could be activated after stimulation with PMA and ionomycin indicating the functionality of the cells. Treatment with an anti-IL-15 antibody induced a reduction in proliferation of late-stage NK cells as shown by EdU staining. This led to significantly dose dependent reduction in the number of circulating stage 4 - 6 NK cells in the system after one week of treatment. This effect was partially reversible after a two-week treatment-free period.

Discussion

In summary, the presented model enables investigation of human NK cell development in the bone marrow and provides a basis to study related diseases and drug response effects in a microenvironment that is designed mimic human physiology.
Programmed cell death markers in COVID-19 survivors with and without sepsis
Authors: Mallarpu Chandra Shekar , Chelluri Srinivasa Ikswaja , Katragadda Tapaswi Krishna , Singarapu Maneendra , Chelluri Lakshmi Kiran , Madiraju Charitha
Published: February 2025

Introduction

Sepsis remains a leading cause of mortality, especially in COVID-19 patients, due to delayed diagnosis and limited therapeutic options. While the mechanisms of programmed cell death (PCD) in COVID-19 and sepsis are complex, understanding the molecular markers involved in these processes may aid in assessing disease severity. This study aimed to investigate the roles of PCD markers, inflammatory cytokines, and MHC molecules in distinguishing disease severity in COVID-19 patients with and without sepsis.

Methods

The study involved adult patients (≥18 years) who survived COVID-19, grouped into four cohorts: COVID-19 with sepsis (C19wSepsis), COVID-19 without sepsis (C19NoSepsis), sepsis alone, and healthy controls. Serum and peripheral blood mononuclear cells (PBMCs) from each cohort were analyzed using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. PCD markers (caspase-3, caspase-1, MLKL, LC3B, p62/SQSTM1), inflammatory cytokines (IL-1-beta, IFN-gamma), and MHC molecules (MHC I-A, MHC II-DRB1) were assessed. Statistical analyses were performed to evaluate differences in marker levels between and within cohorts.

Results

The analysis identified two distinct molecular signatures associated with disease severity. The first signature, characterized by elevated levels of secreted markers of PCD, IL-1-beta, IFN-gamma, MHC I-A and MHC II-DRB1, was common to the C19wSepsis and C19NoSepsis cohorts. The second signature, which was more prominent in the cellular markers of PCD (caspase-1, caspase-3, MLKL, p62/SQSTM1), was uniquely associated with the C19wSepsis cohort.

Conclusion

These findings provide insight into the molecular signatures distinguishing immune responses in COVID-19-related sepsis and may serve as valuable biomarkers for assessing disease severity, while guiding therapeutic interventions in critical care settings.
Impact of hyperhydration on fluid overload and hematopoietic cell transplant after post-transplant cyclophosphamide-based graft-versus-host-disease prophylaxis
Authors: Samuels Diana T. , Yao Janny M. , Samara Yazeed , Yang Dongyun , Mokhtari Sally , Tiemann Katrin , Otoukesh Salman , Arslan Shukaib , Pourhassan Hoda , Wu Stephanie , Blackmon Amanda , Agrawal Vaibhav , Amanam Idoroenyi , Ali Haris , Salhotra Amandeep , Aldoss Ibrahim , Ball Brian , Koller Paul , Aribi Ahmed , Sandhu Karamjeet , Pullarkat Vinod , Artz Andrew , Smith Eileen , Stewart Forrest , Becker Pamela , Stein Anthony , Marcucci Guido , Forman Stephen J. , Nakamura Ryotaro , Al Malki Monzr M.
Published: February 2025

Introduction

Hemorrhagic cystitis (HC) is an early complication after hematopoietic cell transplant (HCT) with post-transplant cyclophosphamide (PTCy). Hyperhydration can reduce HC, but may lead to fluid overload (FO), which has been associated with higher non-relapse mortality (NRM) after HCT.

Methods

The objectives of this study were to grade FO between days 3 and 8 based on weight gain, diuretic therapy, and FO-related organ dysfunction and analyze the impact of FO on non-relapse mortality (NRM) and subsequently on overall survival (OS) of patients undergoing HCT with PTCy-based GvHD prophylaxis.

Results

Two hundred seventy-five patients who received PTCy at City of Hope from 2009 to 2018 were included. A majority, 270 (98%) patients were diagnosed with early FO from day 3-8 post HCT, of whom 248 (92%) experienced mild to moderate (grade 1-2) FO, and 22 (8%) experienced severe (grade 3-4) FO. Day 100 NRM was significantly higher in patients with grade 3-4 FO compared to patients with grade 0-1 (59.1 vs 1.7%, CI: 0.006-0.053p<0.001) and grade 2 (59.1 vs 8.8%, CI: 0.043-0.178, p<0.001) FO. At 2 years, OS and DFS were significantly lower in patients who experienced grade 3-4 FO compared to patients who had grade 0-1 FO (31.8% vs 68.2%, CI: 0.616-0.755, p<0.001) and grade 2 FO (31.8% vs 62.5%; CI: 0.527-0.741, p<0.001). Additionally, each 5% weight gain from baseline was associated with higher NRM (HR=1.91, 95%CI: 1.64-2.23, p<0.001).

Conclusion

Almost all patients undergoing hyperhydration for PTCy-induced HC will present with FO. Grade 3-4 FO is uncommon and associated with poor clinical outcomes. Weight gain could be used as an early and possibly modifiable indicator of FO.
Insights into the diversity and conservation of the chB6 alloantigen
Authors: Funk Phillip E.
Published: February 2025

The bursa of Fabricius has been a durable model of B lymphocyte development. Yet there are unique aspects of B- lymphocyte development in the bursa that remain to be elucidated, and these may reveal important functional differences in the avian system and distinct evolutionary mechanisms from the canonical murine and human models of B- lymphocyte development. Our laboratory has been interested in the function of the chB6 alloantigen. ChB6 has three defined alleles and is present on B lymphocytes in chicken from their earliest development at ED 12. ChB6 continues to be expressed through B- lymphocyte ontogeny as well as on a subset of macrophages. We have shown that chB6 ligation by antibody leads to rapid apoptosis. Transfection of cDNA- encoding chB6 replicates this in mammalians cells, suggesting a common signaling pathway, but there remain no clear mammalian homologues. Structurally, the extracellular domain of chB6 is similar to mammalian SLAM (signaling lymphocyte activation molecules) proteins and chB6 partitions into lipid rafts in close proximity to the B- cell receptor. The lack of homology within the intracellular domain remains puzzling. Utilizing genomic resources, we have found a number of similar molecules in both birds and reptiles; however, they show greater conservation in the intracellular domain, including an SH3 motif that we have shown to be critical in inducing apoptosis.
Does the digital economy reduce shipping-related pollution? Evidence from coastal port cities in China
Authors: Ding Xingong , Song Jiaqi , Zhu Nian , Ji Xina
Published: February 2025

Air pollution caused by shipping-related activities has adversely affected public health and environmental quality in port cities. However, applying digital technologies offers new pathways to mitigate such pollution. Based on panel data from 52 coastal port cities in China from 2016 to 2020, this study employs a two-way fixed effects model to analyze the impact of the digital economy on shipping-related PM2.5 pollution. Additionally, a panel threshold model is used to examine the threshold effect of port size in the relationship between the digital economy and shipping-related pollution. Heterogeneity analysis is further conducted from two dimensions—vessel types and PM2.5 components—to explore the variations in the digital economy’s emission reduction effects. The results show that the development of the digital economy significantly reduces shipping-related PM2.5 pollution levels, and this emission reduction effect strengthens as port size expands. Furthermore, there are significant differences in the emission reduction effects across different vessel types and PM2.5 components. These findings contribute to understanding the mechanisms through which the digital economy mitigates shipping-related pollution and provide a scientific basis and policy support for promoting the green development of port cities and the shipping industry.
The role of Apolipoprotein E4 on cognitive impairment in Parkinson’s disease and Parkinsonisms
Authors: Rosal Angenelle Eve , Martin Sarah L. , Strafella Antonio P.
Published: February 2025

Cognitive impairment is a prevalent non-motor symptom of Parkinson’s disease (PD), increasing the risk of dementia as the disease progresses. Despite its clinical significance, the etiology of cognitive impairment in PD remains unclear. Apolipoprotein E4 (APOE4), a well-known genetic risk factor of Alzheimer’s disease, has been studied for its potential role in PD-related cognitive impairment. However, findings have been conflicting and thus inconclusive, highlighting a need to critically evaluate the current research. Several studies using neuroimaging modalities have explored the brains of individuals with PD and atypical parkinsonian disorders who have APOE4. Some of these studies have identified distinct neuropathological changes that have been previously reported to be associated with cognitive impairments in those with Parkinsonisms. Here, we review the role of APOE4 on cognitive impairment in PD and atypical Parkinsonisms using neuroimaging evidence. We will examine how APOE4 may contribute to pathological changes within the brain and its association with cognitive impairment.
Serum HDL-C levels in children with epilepsy: a single-center retrospective study
Authors: Guo Hong-Li , Dong Na , Hu Ya-Hui , Qiu Jin-Chun , Jiang Zhen-Zhou , Liu Qian-Qi , Lu Xiao-Peng , Chen Feng
Published: February 2025

Purpose

This study aims to compare the difference in serum high-density lipoprotein cholesterol (HDL-C) levels between children with epilepsy and healthy children and to assess its potential influencing factors.

Methods

For comparison, we retrospectively collected data on 1,002 children with epilepsy who visited the Department of Neurology at the Children’s Hospital of Nanjing Medical University. Additionally, we included 127 healthy children who underwent routine health examinations at our hospital’s Health Examination Center. This study also incorporated 98 recently diagnosed epilepsy patients who had not yet received treatment with anti-seizure medications (ASMs) as a source of baseline data. Demographic information and laboratory test results were retrieved from the hospital information system. The Kolmogorov–Smirnov test, the Mann–Whitney test, the Fisher’s exact test, odds ratios (OR), Spearman or Pearson correlation coefficients, and post-hoc analysis were used to conduct statistical analysis.

Results

Healthy children exhibited significantly higher serum levels of HDL-C compared to children with epilepsy and the baseline values. Notably, a higher percentage of children with epilepsy exhibited a low HDL-C levels (<1.0 mmol/L) compared to healthy children, showing an increased risk of dyslipidemia (OR, 2.773; 95% CI, 0.9879–7.457). The type of ASMs had a notable effect on serum HDL-C levels, particularly with hepatic enzyme-inducing ASMs like oxcarbazepine, which significantly raised the serum HDL-C levels. The serum HDL-C levels were also associated with factors such as age, epilepsy history, and brain magnetic resonance imaging findings. Additionally, there was a weak negative association between serum vitamin D levels and serum HDL-C levels (R = -0.37, p = 0.0014). Moreover, children who received vitamin D supplementation demonstrated a higher level of HDL-C than those without such supplementation.

Conclusion

Serum HDL-C levels are notably lower in children with epilepsy than in healthy children. Treatment with ASMs can partially increase the serum HDL-C levels, potentially approaching those found in healthy children. Therefore, the decrease in serum HDL-C levels in children with epilepsy irrespective of receiving ASMs treatment should warrant ongoing attention.
Impacts of sarcopenia on adverse events and prognosis in Chinese patients with esophageal cancer undergoing chemoradiotherapy
Authors: Qu Jiaoyue , Liu Yang , Yuan Yin , Yu Zhao , Ding Jianming , He Zelai , Wang Gengming
Published: February 2025

Background

Sarcopenia is a common indicator of systemic nutritional status in patients with cancer progression. This study investigated the impacts of sarcopenia on adverse effects and prognosis of sarcopenia on patients with esophageal cancer receiving chemoradiotherapy.

Methods

The clinical data of 158 patients with initially diagnosed esophageal cancer who received chemoradiotherapy were collected, and nutritional indexes and inflammatory markers were calculated. The cross-sectional areas of the skeletal muscle, subcutaneous fat and visceral fat were calculated using computed tomography (CT) images of the midpoint of the third lumbar (L3) vertebra. The incidence of adverse events, response evaluation, 1-year and 3-year overall survival (OS) and progression-free survival (PFS) were compared between sarcopenia group and non-sarcopenia groups.

Results

This study included 158 patients, 103 (71.5%) in the sarcopenia group and 45 (28.5%) in the non-sarcopenia group. The last follow-up date was January 31, 2024. The median follow-up time was 36 months for all patients. The chi-square test revealed no significant difference in the incidence of serious adverse events between the two groups. The complete response rates (CR) of patients in the sarcopenia and non-sarcopenia groups 1 month after chemoradiotherapy were 2.7 and 13.3%, respectively, p = 0.017, and the difference was statistically significant. Moreover, the objective response rates (ORR) were 38.9 and 60.0%, respectively (χ2 = 5.770, p = 0.016). The median survival time for all patients was 36 months [95% Confidence Interval CI 24–48]. Univariate analysis (Cox proportional risk model) showed that sarcopenia, KPS score, albumin level, T stage, and N stage were correlated with patients’ OS. Multivariate analysis showed that sarcopenia (Hazard Ratio HR 2.84, 95%CI [1.45–5.57], p = 0.002), KPS score, albumin level and N stage were independent prognostic factors for OS.

Conclusion

Sarcopenia reduced OS in patients with EC treated with chemoradiotherapy. It can be used as an independent indicator to predict the OS of such patients, which may help in developing optimal treatment strategies.
Reversal of chemotherapy resistance in gastric cancer with traditional Chinese medicine as sensitizer: potential mechanism of action
Authors: Zhou Chencong , Wu Kaihan , Gu Meng , Yang Yushang , Tu Jiatao , Huang Xuan
Published: February 2025

Gastric cancer (GC) remains one of the most common types of cancer, ranking fifth among cancer-related deaths worldwide. Chemotherapy is an effective treatment for advanced GC. However, the development of chemotherapy resistance, which involves the malfunction of several signaling pathways and is the consequence of numerous variables interacting, seriously affects patient treatment and leads to poor clinical outcomes. Therefore, in order to treat GC, it is imperative to find novel medications that will increase chemotherapy sensitivity and reverse chemotherapy resistance. Traditional Chinese medicine (TCM) has been extensively researched as an adjuvant medication in recent years. It has been shown to have anticancer benefits and to be crucial in enhancing chemotherapy sensitivity and reducing chemotherapy resistance. Given this, the mechanism of treatment resistance in GC is summed up in this work. The theoretical foundation for TCM as a sensitizer in adjuvant treatment of GC is established by introducing the primary signal pathways and possible targets implicated in improving chemotherapy sensitivity and reversing chemotherapy resistance of GC by TCM and active ingredients.
Real-world treatment and retreatment patterns and outcomes in patients with advanced or metastatic non-small cell lung cancer following nivolumab monotherapy in second line or later in France: an I-O Optimise analysis
Authors: Justeau Grégoire , Chouaid Christos , Debieuvre Didier , Audigier-Valette Clarisse , Quantin Xavier , Léna Hervé , Bosquet Lise , Girard Nicolas , Schoemaker Minouk J. , Mella Marta , Pinto Correia Bárbara , Rault Caroline , Daumont Melinda J. , Penrod John R. , Lee Adam , Pérol Maurice
Published: February 2025

Introduction

This study describes treatment and retreatment patterns and outcomes in patients in France following nivolumab as a second-line or later (2L+) treatment in locally advanced or metastatic non-small cell lung cancer (LAM NSCLC).

Materials and methods

This analysis included adults with tumor, node, metastasis stage IIIB–IV NSCLC (as defined in the 7th or 8th edition American Joint Committee on Cancer/Union for International Cancer Control) treated with nivolumab monotherapy in 2L+ using data from the retrospective Epidemiological-Strategy and Medical Economics Lung Cancer database. The inclusion period was from January 1, 2015, to September 30, 2020, with a follow-up until September 30, 2021. Analyses were stratified according to the duration of index nivolumab treatment and tumor programmed death ligand 1 expression levels.

Results

In total, the study included 4,001 patients (68% male; mean age [standard deviation] at index date, 63.6 [9.7] years) with a median follow-up of 34.3 months. The median nivolumab duration was 2.5 months (interquartile range, 1.4–6.3). The median overall survival (OS) from nivolumab initiation was 10.2 months (95% confidence interval [CI], 9.6–10.8). The median real-world progression-free survival and time to treatment discontinuation or death (95% CI) were 2.2 (2.1–2.3) and 2.7 (2.5–2.8) months, respectively. In total, 2,985 (74.6%) patients discontinued index nivolumab treatment: 226 (7.6% of discontinuers) received a further immune checkpoint inhibitor (ICI; 12.3% of discontinuers receiving further systemic treatment), and 1,604 (53.7%) received chemotherapy and/or targeted therapy. The proportion of ICI-retreated patients was the highest among those with the longest index treatment duration (15.8% among discontinuers receiving ≥26 weeks’ index nivolumab). The median OS from retreatment was longer in the resumption (ICI restart without another therapy for ≥6 weeks) compared with the rechallenge (ICI restart following non-ICI therapy) patient subgroup.

Conclusion

Few patients with LAM NSCLC in France received ICI retreatment following index nivolumab discontinuation, but the proportion increased with a longer duration of index nivolumab.
Research progress on artificial intelligence technology-assisted diagnosis of thyroid diseases
Authors: Yang Lina , Wang XinYuan , Zhang Shixia , Cao Kun , Yang Jianjun
Published: February 2025

With the rapid development of the “Internet + Medical” model, artificial intelligence technology has been widely used in the analysis of medical images. Among them, the technology of using deep learning algorithms to identify features of ultrasound and pathological images and realize intelligent diagnosis of diseases has entered the clinical verification stage. This study is based on the application research of artificial intelligence technology in medical diagnosis and reviews the early screening and diagnosis of thyroid diseases. The cure rate of thyroid disease is high in the early stage, but once it deteriorates into thyroid cancer, the risk of death and treatment costs of the patient increase. At present, the early diagnosis of the disease still depends on the examination equipment and the clinical experience of doctors, and there is a certain misdiagnosis rate. Based on the above background, it is particularly important to explore a technology that can achieve objective screening of thyroid lesions in the early stages. This paper provides a comprehensive review of recent research on the early diagnosis of thyroid diseases using artificial intelligence technology. It integrates the findings of multiple studies and that traditional machine learning algorithms are widely used as research objects. The convolutional neural network model has a high recognition accuracy for thyroid nodules and thyroid pathological cell lesions. U-Net network model can significantly improve the recognition accuracy of thyroid nodule ultrasound images when used as a segmentation algorithm. This article focuses on reviewing the intelligent recognition technology of thyroid ultrasound images and pathological sections, hoping to provide researchers with research ideas and help clinicians achieve intelligent early screening of thyroid cancer.
Perioperative inflammatory index differences between pulmonary squamous cell carcinoma and adenocarcinoma and their prognostic implications
Authors: Liu Yi , Cui Songping , Wang Jing , Hu Bin , Chen Shuo
Published: February 2025

Background

Perioperative inflammatory indices reflect systemic inflammatory responses and have been linked to cancer progression and prognosis. This study aims to explore the differences in perioperative inflammatory indices between lung squamous cell carcinoma (LSCC) and adenocarcinoma (LUAD) and their association with long-term outcomes.

Methods

This study included 287 lung cancer patients who underwent curative resection between June 2016 and December 2017, comprising 61 cases of LSCC and 226 cases of LUAD. Perioperative baseline information and inflammatory cell counts were collected. Patients were followed up for a median duration of 76 months, during which disease-free survival (DFS) and overall survival (OS) were recorded. Cox regression analysis was used to evaluate the prognostic significance of inflammatory factor levels.

Results

Significant differences were observed in white blood cell count and systemic inflammation response index (SIRI) between LSCC and LUAD (P < 0.05). Regression analysis identified age (OR=2.096, P=0.004), postoperative day 1 D-dimer level (OR=1.550, P<0.001), and Platelet-to-lymphocyte ratio (PLR) (OR=1.901, P=0.031) as independent risk factors for perioperative venous thromboembolism (VTE). Furthermore, open surgical approach (HR=2.437, P=0.016), tumor type (LSCC; HR=2.437, P=0.016), and PLR (HR=1.534, P=0.019) were independent risk factors for DFS.

Conclusion

Inflammatory index is key predictors of perioperative VTE and DFS in lung cancer, emphasizing their critical role in prognosis.
A novel nomogram based on complement C3 to predict the overall survival of early-stage hepatocellular carcinoma patients with microvascular invasion-positive undergoing curative resection
Authors: Xia Guoyi , Yu Zeyan , Lu Shaolong , Wang Xiaobo , Zhao Yuanquan , Chen Jie
Published: February 2025

Purpose

This investigation aimed to create a new nomogram based on complement C3 to forecast 1-, 3-, and 5-year overall survival (OS) rates in patients with early-stage hepatocellular carcinoma (HCC) exhibiting microvascular invasion (MVI) post-curative surgery.

Methods

This study encompassed 1234 patients treated with resection at the Affiliated Cancer Hospital of Guangxi Medical University. The cohort for primary included 865 patients from December 2015 to December 2019, while the validation cohort comprised 369 patients. Follow-ups were conducted regularly until December 2024. Variables predicting survival were identified using Cox regression analyses, and based on these, a nomogram was constructed. This nomogram’s accuracy was assessed via time-dependent ROC curves, calibration curves and KM curve analyses.

Results

Investigations identified complement C3, PT, the presence of cirrhosis, tumor capsule, and MVI-M2 as distinct predictors of survival in HCC patients. Based on these findings, a predictive nomogram was constructed and validated, aimed at estimating the 1-, 3-, and 5-year OS. The efficacy of the nomogram was validated through analyses with ROC curves, calibration curves, each demonstrating positive outcomes. Additionally, KM curve analysis effectively separated the patient populations into two prognostic risk categories within both the primary and validation cohorts.

Conclusion

In conclusion, a new nomogram has been developed and corroborated through multivariate Cox regression analysis, aimed at estimating overall survival for patients in early stages of microvascular invasion following surgical resection. This tool has proven to be more effective in forecasting survival outcomes for such patients post-curative surgery.
A numerical study of design and off-design operations of SHM1 airfoil
Authors: Sengupta Aditi , Guha Abhijeet
Published: February 2025

Natural laminar flow airfoils are essential technologies designed to reduce drag and significantly enhance aerodynamic performance. A notable example is the SHM1 airfoil, created to meet the requirements of the small-business jet by Honda R&D. This airfoil has undergone extensive testing across various operational conditions, including low-speed wind tunnel tests and flight tests across a range of Reynolds numbers and free-stream Mach numbers. Additionally, investigations into drag-divergence behavior have been conducted using a transonic wind tunnel, with subsequent studies focusing on transonic shock boundary layer interactions through both experimental and numerical approaches. This study employs a series of numerical simulations to analyze the flow physics and aerodynamic performance across different free-stream Mach numbers in the subsonic and transonic regimes. The analysis offers a comprehensive overview of the aerodynamic performance by making use of instantaneous and time-averaged load and pressure distributions, highlighting the different flow structures (trailing edge vortices, Kutta waves, shock waves - both normal and oblique) and associated time scales in the unsteady flow field and how these impact the performance and extent of separated flow on the SHM1 airfoil. This is achieved by examining computed instantaneous numerical Schlieren for various design conditions (such as low speed, climb, and cruise) and off-design scenarios (including transonic shock emergence, drag-divergence, and shock-induced separation). The dominant time scales, the time-averaged load distributions and boundary layer parameters are compared to provide a comprehensive overview of the SHM1’s aerodynamics, establishing benchmark results for optimization of various flow separation and shock control techniques.
Caregiver determinants and capacity for participation in constraint-induced movement therapy
Authors: Moore Hunter G. , Ayala Amy , Aravamuthan Bhooma R. , Smith Alyssa E. , Ramey Sharon L. , Hoyt Catherine R.
Published: February 2025

Aim

Hemiplegic cerebral palsy affects 1 in every 1,100 children, making it the most common pediatric motor disability. Constraint-Induced Movement Therapy (CIMT) is an evidence-based intervention that significantly improves upper extremity function when implemented with high fidelity. Despite its effectiveness, CIMT's intensive nature—requiring daily therapy for up to twenty days—limits its availability. This study examined caregivers’ perspectives on implementing and adapting home-based CIMT to identify practical solutions for improving intervention accessibility.

Method

Caregivers of a child who has a diagnosis associated with upper extremity motor impairment consistent with cerebral palsy were recruited from the Cerebral Palsy Center at the St. Louis Children's Hospital. Caregivers completed a semi-structured interview to share their CIMT experiences, as well as their ideas and opinions related to modified versions of CIMT. All interviews were coded and analyzed for themes using descriptive analysis.

Results

Twelve interviews were conducted and revealed that caregivers would be interested in CIMT with an at-home model. Those who had experience with CIMT stated they found meaningful results from their participation in CIMT. Caregivers communicated potential challenges such as their child remaining engaged in at-home therapy, caregiver confidence in implementing the therapy, and the time required for implementing caregiver-led, home-based CIMT.

Interpretation

Study findings identified that caregivers see value in a modified, at-home CIMT program. Developing a modified version of CIMT is needed to increase access to this beneficial intervention.
The clinical value of α-hydroxybutyrate dehydrogenase, cardiac troponin I, and B-type natriuretic peptide in perioperative diagnosis of heart failure in children with congenital heart disease
Authors: Yin Jun , Wang Qingsong , Xu Shuqiong , Wang Junru , Huang Shihua , Shen Junhong , Yuan Tao , Luo Tongyong , Wang Xianmin
Published: February 2025

Objective

This study evaluates the clinical value of α-Hydroxybutyrate Dehydrogenase (α-HBDH), Cardiac Troponin I (cTnI), and B-Type Natriuretic Peptide (BNP) in the perioperative diagnosis of heart failure in children with congenital heart disease (CHD).

Methods

A retrospective analysis was performed on data from 107 children with CHD who underwent surgery between March 2022 and March 2023. Patients were categorized based on the European Society of Cardiology (ESC) cardiac function grading into three groups (Grades I–III) and further into heart failure (HF) and non-HF groups. Preoperative and postoperative levels of α-HBDH, cTnI, and BNP were compared across cardiac function grades and HF status. The diagnostic value of these biomarkers was assessed using receiver operating characteristic (ROC) curve analysis.

Results

Preoperative levels of α-HBDH, cTnI, and BNP were significantly higher in the HF group than in the non-HF group (all P < 0.05). These markers also increased with cardiac function severity, being highest in Grade III. Postoperatively, α-HBDH, CKMB, and BNP remained elevated in severe cases, correlating with worsening function (all P < 0.05). The ROC analysis showed that among the preoperative cardiac biomarkers in children with CHD, whether assessed individually or in combination, the combined detection of cTnI and BNP exhibited the highest diagnostic value for perioperative heart failure, with an AUC of 0.883.

Conclusion

In children with CHD, preoperative levels of α-HBDH, cTnI, and BNP during the perioperative period are closely correlated with cardiac function, significantly increasing with the severity of cardiac dysfunction. These biomarkers have important clinical value for diagnosing heart failure, with the combined detection of cTnI and BNP demonstrating the highest diagnostic efficacy.
Case Report: White–Sutton syndrome and cannabidiol, an update on a reported patient with a successful response to off--label therapy
Authors: Perilli Lorenzo , Carbone Samanta , Minerva Michele , Rossi Margherita Maria , Curcio Maria Rosaria , Lotti Federica , Grosso Salvatore
Published: February 2025

White–Sutton syndrome (WSS), associated with POGZ gene mutations, is a rare genetic disorder characterized by a spectrum of phenotypic features, including intellectual disabilities, developmental delays, and epilepsy. A case report described a female patient diagnosed with WSS who experienced seizures resistant to conventional antiseizure medications. Despite various therapeutic attempts, including valproate, topiramate, levetiracetam, clobazam, rufinamide, and vigabatrin, the patient's seizures persisted. After initiating an off-label treatment with cannabidiol (CBD), the patient achieved complete remission from seizures. Following significant clinical improvement, CBD therapy was discontinued by the parents against medical advice, leading to seizure recurrence. Upon reinstatement of CBD, the patient once again experienced successful seizure control. This report emphasizes the need for further investigation into the off-label use of CBD, as an adjunctive therapy in pediatric individuals with drug-resistant epilepsy associated with WSS. Although CBD shows promise in other epileptic syndromes, this case highlights its potential effectiveness in this specific condition. This manuscript aims to contribute to the understanding of WSS and advocate for further research into novel treatments, particularly the role of CBD in managing epilepsy within this complex clinical context.
Perioperative comparison of whether the liver was lifted out of the abdominal cavity in Kasai surgery
Authors: Xu Ke , Gao Juan , Chen Xiaoyi , Fang Yifan , Wu Dianming , Lin Yu
Published: February 2025

Objective

To compare the perioperative effect of whether the liver is lifted out of the abdominal cavity during Kasai surgery in patients with biliary atresia type III.

Methods

We retrospectively analyzed 29 males and 33 females aged 2.2 ± 0.6 months who underwent kasai surgery from June 2019 to December 2022 at Fujian Provincial Children's Hospital. Among the 62 children with the liver not lifted out of the abdominal cavity into the experimental group (n = 31), and those with the liver lifted out of the abdominal cavity into the control group (n = 31). We compared the operation time, surgical incision length, intraoperative blood pressure and body temperature fluctuations, average daily peritoneal drainage, postoperative length of hospital stay, postoperative complications, postoperative total bilirubin level, and autologous liver survival rate between the two groups.

Results

The length of the surgical incision in the control group (7.5 ± 1.2 cm) was longer than that in the experimental group (6.7 ± 1.1 cm), and the difference was statistically significant (t = 2.88, P = 0.005). The fluctuations in blood pressure in the control group (before and after the liver was lifted out of the abdominal cavity) (24.3 ± 7.7 mmHg) were greater than that in the experimental group (before and after hooking to expose the hilar area) (20.2 ± 6.0 mmHg), which was a statistically significant difference (t = 2.32, P = 0.023). The temperature fluctuations in the control group (before and after the liver was lifted out of the abdominal cavity) (0.3 ± 0.1°C) was greater than that in the experimental group (before and after the liver was lifted out of the abdominal cavity) (0.1 ± 0.1°C), showing a statistically significant difference (t = 8.19, P = 0.000). The average daily abdominal drainage in the control group was 71.3 ± 33.5 ml, which was greater than that in the experimental group (49.2 ± 49.6 ml), and the difference was statistically significant (t = 2.06, P = 0.044). The number of days of postoperative hospital stay in the control group (18.2 ± 4.8 days) was significantly more than that in the experimental group (15.8 ± 3.8 days), with a statistically significant difference (t = 2.18, P = 0.033).

Conclusion

In children with biliary atresia type III, the liver is not lifted out of the abdominal cavity during Kasai surgery increases the safety of surgery and reduces the length of hospital stay.