bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factor analysis and nomogram construction of postoperative complications for patients with locally advanced gastric cancer who received neoadjuvant immunotherapy and chemotherapy
Authors: Cui Hao , Zhang Sijin , Sun Linde , Yuan Zhen , Xu Qixuan , Gao Jingwang , Chen Lin , Cui Jianxin , Wei Bo 
Published: July 2024

IntroductionThe combination of neoadjuvant immunotherapy and chemotherapy (NICT) has become a common treatment regimen for locally advanced gastric cancer (LAGC). However, the safety and efficacy of radical gastrectomy following NICT (NICT-G) remain controversial. This study aimed to analyze the risk factors influencing postoperative complications (POCs) after NICT-G. Additionally, it aimed to construct a nomogram to provide a clinical reference for predicting POCs.MethodsThis study included 177 patients who received NICT-G at the Chinese PLA General Hospital First Medical Center from January 2020 to January 2024. Univariable and multivariable logistic regression models were used to evaluate the risk factors influencing POCs, and a nomogram model was constructed. To evaluate the discrimination and accuracy of the nomogram model, the area under the receiver operating characteristic curve (AUC) and the calibration curve were measured.ResultsIn 177 patients who received NICT-G, the pathological complete response and major pathological response rates were 15.8% and 45.2%, respectively, whereas the rates of the overall and severe treatment-related adverse events were 71.8% and 15.8%, respectively. In addition, 43 (24.3%) patients developed overall POCs (Clavien–Dindo classification ≥ II). Univariable and multivariable logistic analyses showed that age ≥70 years, greater estimated blood loss, platelet/lymphocyte ratio (PLR) ≤196, neutrophil/lymphocyte ratio (NLR) &gt;1.33, non-R0 resection, and body mass index (BMI) &lt; 18.5 kg/m2 were independent risk factors for overall POCs (p &lt; 0.05). The nomogram model developed using the abovementioned variables showed that the AUC (95% confidence interval [CI]) was 0.808 (95% CI): 0.731–0.885 in predicting the POC risk. The calibration curves showed that the prediction curve of the nomogram was a good fit for the actual POCs (Hosmer–Lemeshow test: χ2 = 5.76, P = 0.451).ConclusionThe independent risk factors for overall POCs in the NICT-G were age ≥ 70 years, greater estimated blood loss, PLR ≤ 196, NLR &gt; 1.33, non-R0 resection, and BMI &lt; 18.5 kg/m2. The nomogram model developed based on the abovementioned indicators showed better accuracy in predicting the POC risk.
Effect of the health and wellness Kneipp concept on health promotion and reduction of sick days for kindergarten children: a cluster randomized controlled trial protocol
Authors: Gerganova Marinela , Schepanski Steven , Bogdanski Martin , Kandil Farid I. , Tekath Angela , Jeitler Michael , Stritter Wiebke , Blakeslee Sarah B. , Seifert Georg 
Published: July 2024

BackgroundThe holistic health and wellness Kneipp concept, has a long tradition in Europe with demonstrated health benefits. Based on the five elements of the Kneipp concept, kindergartens in and around Germany are used to certify “Kneipp Kindergartens” that practice regular Kneipp applications and activities: cold water applications, exercise, nutrition, herbs and mind-body interventions. Little is known about the potential health benefits for children, however. This study protocol describes our study design and intervention of the Kita Kneipp Study to investigate the effect of the Kneipp concept on kindergarten children aged 2–6 years.Methods and designThe Kita Kneipp Study, registered with the German Clinical Trial Register (DRKS-ID: DRKS00029275), is a confirmatory, mixed-method, two-armed, waitlist, clinical, cluster randomized controlled trial (RCT). Kindergartens in Berlin, Germany that would like to implement the Kneipp concept into their facility will be recruited and randomized to the intervention or control group. Changes in the number of kindergarten sick days will be the primary outcome measure. Kindergarten attendance and reason for absence including illness will be collected on a weekly basis at two time points for 6 weeks from the parents and kindergarten directors: baseline and 1 year after baseline. Secondary outcomes will measure cold symptoms through the Common Cold Questionnaire (CCQ) and National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE) Scales describing gastroenterological-based symptoms Kindergarten educator sick days will be aggregately reported for the same time period. Kneipp concept activities will be recorded on a weekly basis over the one-year intervention period. To understand the experience of Kneipp concept implementation and possible changes in the kindergarten, expert interviews will be conducted with intervention kindergarten educators and focused ethnographies will be planned to observe and analyze the intervention activities.DiscussionThis mixed method study design has potential to help identify if the Kneipp concept can be used for salutogenic purposes among young children and provide insights and experience of the implementation and practicing a holistic health and wellness concept in a kindergarten setting.
Age-specific disparity in insomnia among COVID-19 patients in Fangcang shelter hospitals: a population-based study in Shanghai, China
Authors: Shi Ruizi , Wang Yihui , Chen Ying , Yang Zhitao , Jing Feng , Shang Hanbing , Chen Erzhen , Zhou Ying 
Published: July 2024

BackgroundFangcang shelter hospitals are quarantine facilities offering primary medical treatment for mild and asymptomatic SARS-CoV-2 cases. Little is known about the age-specific prevalence of insomnia among patients in Fangcang shelter hospitals, particularly in older age groups.MethodsThis cross-sectional study was conducted in the three largest Fangcang shelter hospitals during the lockdown period, from March to May 2022, in Shanghai. The patients’ demographic and medical information was recorded. Insomnia was defined according to the prescriptions for zolpidem and estazolam. The overall and age-specific prevalence and the risk factors of insomnia were investigated through regression models.ResultsA total of 2,39,448 patients were included in this study (59.09% of the patients were male, the median age was 42, and 73.41% of the patients were asymptomatic), with the prevalence of insomnia being 3.1%. The prevalence of insomnia varied across different age groups (&lt;18 years: 0.23%, 18–64 years: 2.64%, and ≥65 years: 10.36%). SARS-CoV-2 vaccine, regardless of the number of doses, was significantly associated with a decreased risk of insomnia for the group aged ≥65 years. Three doses of the vaccine reduced the risk of insomnia for patients aged 18–64 years. An extra day in the hospital significantly increased the risk of insomnia by approximately 10% for all age groups. Mild symptoms were significantly associated with a higher risk of insomnia among patients aged &lt;65 years old, while being male and residing in the surrounding area were negatively associated with insomnia for all adults.ConclusionThis study observed that older patients were a high-risk population for developing insomnia in Fangcang shelter hospitals. SARS-CoV-2 vaccination might decrease the risk of insomnia in adults, especially the older adult, which indicates the benefits of vaccination for reducing insomnia among infected patients.
The impact of inhalation versus total intravenous anesthesia on the immune status in patients undergoing breast cancer surgery: a double-blind randomized clinical trial (TeMP)
Authors: Kadantseva Kristina , Subbotin Valery , Akchulpanov Roman , Berikashvili Levan , Yadgarov Mikhail , Zhukova Lyudmila , Kvetenadze Guram , Svitich Oxana , Kukina Polina , Kuznetsov Ivan , Shemetova Mariya , Smirnova Anastasiya , Polyakov Petr , Shebankov Andrey , Likhvantsev Valery 
Published: July 2024

BackgroundBreast cancer (BC) mortality primarily stems from metastases rather than the primary tumor itself. Perioperative stress, encompassing both surgical and anesthetic factors, profoundly impacts the immune system, leading to alterations in neuroendocrine pathways and immune functions, potentially facilitating tumor progression and metastasis. Understanding the immunomodulatory effects of different anesthesia techniques is crucial for optimizing perioperative care in patients with BC. The neutrophil-to-lymphocyte ratio (NLR) serves as one of the key indicators of perioperative immune response.ObjectiveTo compare the effects of inhalation anesthesia (IA) and total intravenous anesthesia (TIVA) on perioperative immune response in BC surgery patients.MethodsIn this randomized, double-blind clinical trial, BC surgery patients were randomized to receive either TIVA with propofol or IA with sevoflurane. The primary endpoint was NLR assessment. Secondary immune parameters measured included natural killer cells, various T cell subsets, B cells, the immuno-regulatory index [T-helpers (CD3+CD4+)/cytotoxic T-cells (CD3+CD8+)], matrix metallopeptidases (MMP-9), complement components, and immunoglobulins, preoperatively and at 1 and 24 hours postoperatively.ResultsThe study included 98 patients (IA: 48, TIVA: 50). The baseline characteristics exhibited remarkable similarity across the groups. No significant difference in absolute NLR values was found between IA and TIVA groups at any time point (1 hour: p = 0.519, 24 hours: p = 0.333). Decreased IgA and IgM levels post-surgery suggested potential negative impacts of IA on humoral immunity compared to TIVA. CRP levels increased more by 24 hours (p = 0.044) in IA compared to TIVA. No significant differences were observed in natural killer cells, T cell subsets, B cells, MMP-9 levels or complement components between groups. Significant differences in the immuno-regulatory index between the TIVA and IA groups at one hour postoperatively (p = 0.033) were not maintained at 24 hours.ConclusionWhile there were no notable differences in NLR among the types of anesthesia, the observed disparities in immunoglobulin content and C-reactive protein levels between groups suggest that we cannot dismiss the potential immunosuppressive effects of inhalational anesthesia in breast cancer surgeries. Further investigation needed to clarify the impact of various anesthesia methods on immune function and their implications for long-term cancer outcomes.
Inflammatory markers as prognostic markers in patients with head and neck squamous cell carcinoma treated with immune checkpoint inhibitors: a systematic review and meta-analysis
Authors: Wang Quan , Yin Xiangzhi , Wang Shengxia , Lu Haijun 
Published: July 2024

BackgroundVarious inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein-to-albumin ratio (CAR), have been linked to the effectiveness of immunotherapy in multiple types of malignancies. We investigated how these inflammatory markers affect the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) receiving immunotherapy.MethodsThe databases PubMed, Embase, and Cochrane were systematically searched up until March 26, 2024, to identify relevant literature. Hazard ratios (HR) and corresponding 95% confidence intervals (CI) were extracted from the eligible studies. Data analysis was conducted using Review Manager and STATA 17.0 software to assess the impact of each indicator on prognosis. Subgroup analysis was performed to explore potential sources of heterogeneity in the data.ResultsThe analysis included sixteen studies with 1316 patients. A higher baseline NLR was significantly associated with poorer overall survival (OS) (pooled HR: 1.55, 95%CI: 1.14-2.11, P=0.006) and progression-free survival (PFS) (pooled HR: 1.59, 95% CI: 1.21-2.10, P&lt;0.05). Furthermore, a high NLR after immunotherapy was strongly correlated with poor OS (pooled HR: 5.43, 95% CI: 3.63-8.12, P&lt;0.01). Additionally, higher baseline C-reactive CAR was significantly associated with worse OS (pooled HR: 2.58, 95% CI: 1.96-3.40, P&lt;0.01).ConclusionThe inflammatory markers NLR and CAR serve as effective prognostic biomarkers for immunotherapy in patients with HNSCC. However, the practical application of clinical detection requires further validation through large-scale prospective studies to confirm these findings and explore the underlying mechanisms.
Laparoscopic pyeloplasty in neonates and infants is safe and efficient
Authors: Langreen S. , Ludwikowski B. , Dingemann J. , Ure B. M. , Hofmann A. D. , Kuebler J. F. 
Published: July 2024

IntroductionDismembered laparoscopic pyeloplasty (LP) is a well-accepted treatment modality for ureteropelvic junction obstruction (UPJO) in children. However, its efficacy and safety in infants, particularly neonates, remain uncertain. To address this significant knowledge gap, we aimed to compare outcomes between a cohort of neonates and infants undergoing LP vs. open pyeloplasty (OP) at less than 6 months and 6 weeks of age.Material and methodsWe conducted a retrospective analysis of data from patients who underwent primary pyeloplasty at our institution between 2000 and 2022. Only patients aged 6 months or less at the time of surgery were included, excluding redo-procedures or conversions. Ethical approval was obtained, and data were assessed for redo-pyeloplasty and postoperative complications, classified according to the Clavien–Madadi classification. A standard postoperative assessment was performed 6 weeks postoperatively. This included an isotope scan and a routine ultrasound up to the year 2020.ResultsA total of 91 eligible patients were identified, of which 49 underwent LP and 42 underwent OP. Patients receiving LP had a median age of 11.4 (1–25.4) weeks, compared to 13.8 (0.5–25.9) weeks for those receiving OP (p &gt; 0.31). Both groups in our main cohort had an age range of 0–6 months at the time of surgery. Nineteen patients were younger than 6 weeks at the time of surgery. The mean operating time was longer for LP (161 ± 43 min) than that for OP (109 ± 32 min, p &lt; 0.001). However, the mean operating time was not longer in the patient group receiving LP at ≤6 weeks (145 ± 21.6) compared to that in our main cohort receiving LP. There was no significant difference in the length of stay between the groups. Four patients after LP required emergency nephrostomy compared to one patient after OP. The rate of revision pyeloplasty in our main cohort aged 0–6 months at surgery was 8% in the patient group receiving LP and 14% in the patient group receiving OP (not significant). Three revisions after LP were due to persistent UPJO, and one was due to stent migration. Only one patient requiring revision pyeloplasty was less than 6 weeks old.ConclusionTo our knowledge, this is one of the largest collectives of laparoscopic pyeloplasty performed in infants, and it is the youngest cohort published to date. Based on our experience, LP in neonates and infants under 6 months appears to be as effective as open surgery.
A novel probiotic formula, BLLL, ameliorates chronic stress-induced depression-like behaviors in mice by reducing neuroinflammation and increasing neurotrophic factors
Authors: Ye Minxiu , Ji Feng , Huang Chao , Li Fu , Zhang Changliang , Zhang Yu , Wang Runxin , Ma Kai , Lu Xu , Wang Hui 
Published: July 2024

Introduction: Probiotics have been recognized for their various biological activities, including antioxidant and anti-inflammatory properties. This study investigates the therapeutic effect of a novel probiotic formula, BLLL, consisting of Bifidobacterium breve, Lactobacillus plantarum, Lactobacillus paracasei, and Lactobacillus helveticus, on chronic stress-induced depression-like behaviors in mice.Methods: The BLLL formula or phosphate-buffered saline (PBS) was given orally at a dose of 2, 4, or 8 × 1010 CFU/kg once daily for 10 days in mice treated with chronic unpredictable stress (CUS) treated or vehicle. Depression-like behaviors were assessed using the sucrose preference test (SPT), the forced swimming test (FST), and the tail suspension test (TST). The mRNA and/or protein expression of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), IL-4, IL-10, and chitinase-3-like protein 3 (CHI3L1, also known as Ym-1), as well as the concentration of nitrite, malondialdehyde (MDA), glutathione (GSH), and brain-derived neurotrophic factor (BDNF) in the hippocampus and medial prefrontal cortex were examined.Results: The BLLL formula treatment at a dose of 8 × 1010 CFU/kg, but not at a dose of 2 or 4 × 1010 CFU/kg, improved CUS-induced depression-like behaviors in mice, as shown by the decrease in immobility time in the TST and FST and the increase in sucrose intake in the SPT. Further analysis revealed that BLLL treatment suppressed the CUS-induced increase in IL-1β, IL-6, and TNF-α mRNA and protein levels, as well as the CUS-induced decrease in IL-4, IL-10, and Ym-1 mRNA and/or protein levels in the hippocampus and medial prefrontal cortex. In addition, treatment with the BLLL formula countered the CUS-induced increase in nitrite and MDA levels and the CUS-induced decrease in GSH content and BDNF concentration in the hippocampus and medial prefrontal cortex.Conclusion: These results demonstrate that the novel probiotic formula BLLL ameliorates chronic stress-induced depression-like behavior in mice by suppressing neuroinflammation and oxido-nitrosative stress in the brain.
Integrating Mendelian randomization and single-cell RNA sequencing to identify therapeutic targets of baicalin for type 2 diabetes mellitus
Authors: Liang Ying-Chao , Li Ling , Liang Jia-Lin , Liu De-Liang , Chu Shu-Fang , Li Hui-Lin 
Published: July 2024

BackgroundAlternative and complementary therapies play an imperative role in the clinical management of Type 2 diabetes mellitus (T2DM), and exploring and utilizing natural products from a genetic perspective may yield novel insights into the mechanisms and interventions of the disorder.MethodsTo identify the therapeutic target of baicalin for T2DM, we conducted a Mendelian randomization study. Druggable targets of baicalin were obtained by integrating multiple databases, and target-associated cis-expression quantitative trait loci (cis-eQTL) originated from the eQTLGen consortium. Summary statistics for T2DM were derived from two independent genome-wide association studies available through the DIAGRAM Consortium (74,124 cases vs. 824,006 controls) and the FinnGen R9 repository (9,978 cases vs. 12,348 controls). Network construction and enrichment analysis were applied to the therapeutic targets of baicalin. Colocalization analysis was utilized to assess the potential for the therapeutic targets and T2DM to share causative genetic variations. Molecular docking was performed to validate the potency of baicalin. Single-cell RNA sequencing was employed to seek evidence of therapeutic targets’ involvement in islet function.ResultsEight baicalin-related targets proved to be significant in the discovery and validation cohorts. Genetic evidence indicated the expression of ANPEP, BECN1, HNF1A, and ST6GAL1 increased the risk of T2DM, and the expression of PGF, RXRA, SREBF1, and USP7 decreased the risk of T2DM. In particular, SREBF1 has significant interaction properties with other therapeutic targets and is supported by strong colocalization. Baicalin had favorable combination activity with eight therapeutic targets. The expression patterns of the therapeutic targets were characterized in cellular clusters of pancreatic tissues that exhibited a pseudo-temporal dependence on islet cell formation and development.ConclusionThis study identified eight potential targets of baicalin for treating T2DM from a genetic perspective, contributing an innovative analytical framework for the development of natural products. We have offered fresh insights into the connections between therapeutic targets and islet cells. Further, fundamental experiments and clinical research are warranted to delve deeper into the molecular mechanisms of T2DM.
Glycerophosphoinositol modulates FGA and NOTCH3 in exercise-induced muscle adaptation and colon cancer progression
Authors: Luo Hongbiao , Luo Wei , Ding Ning , Zhu Huimin , Lai Jiahui , Tang Qingzhu , He Yongheng 
Published: July 2024

ObjectivesFibroleukin (FGA) and NOTCH3 are vital in both exercise-induced muscle adaptation and colon adenocarcinoma (COAD) progression. This study aims to elucidate the roles of FGA and NOTCH3 in phenotypic variations of striated muscle induced by exercise and in COAD development. Additionally, it seeks to evaluate the prognostic significance of these proteins.MethodsGene Set Variation Analysis (GSVA) and protein-protein interaction (PPI) network analysis were employed to identify differentially expressed genes (DEGs). Molecular docking studies were conducted to assess the binding affinities of 39 compounds to the NOTCH3 protein. In vitro assays, including mobileular viability, gene expression, and apoptosis assays, were performed to evaluate the effects of glycerophosphoinositol on FGA and NOTCH3 expression. Additionally, copy number variation (CNV), methylation status, and survival analyses were conducted across multiple cancers types.ResultsThe NOTCH signaling pathway was consistently upregulated in exercise-induced muscle samples. High NOTCH3 expression was associated with poor prognosis in COAD, extracellular matrix organization, immune infiltration, and activation of the PI3K-Akt pathway. Molecular docking identified gamma-Glu-Trp, gamma-Glutamyltyrosine, and 17-Deoxycortisol as strong binders to NOTCH3. Glycerophosphoinositol treatment modulated FGA and NOTCH3 expression, influencing cell proliferation and apoptosis. CNV and methylation analyses revealed specific changes in FGA and NOTCH3 across 20 cancers types. Survival analyses showed strong associations between FGA/NOTCH3 expression and survival metrics, with negative correlations for FGA and positive correlations for NOTCH3.ConclusionFGA and NOTCH3 play significant roles in exercise-induced muscle adaptation and colon cancer progression. The expression profiles and interactions of these proteins provide promising prognostic markers and therapeutic targets. These findings offer valuable insights into the post-translational modifications (PTMs) in human cancer, highlighting novel pharmacological and therapeutic opportunities.