bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of immune-related adverse events on the outcome of advanced gastric cancer patients with immune checkpoint inhibitor treatment
Authors: Zhang Tianhang , Lv Haitao , Li Jiasong , Zhang Shasha , Zhang Jingjing , Wang Siqi , Wang Yingnan , Guo Zhanjun 
Published: December 2024

BackgroundThe occurrence of immune-related adverse events (irAEs) seemed to be associated with better outcomes in advanced gastric cancer (AGC) patients. However, research focusing on the impact of the single-organ irAE (uni-irAE) or multi-organ irAEs (multi-irAEs) on the AGC outcome is relatively limited. In this study, we investigated individually the impact of the different irAEs on AGC survival as well as the co-occurrence patterns of multi-irAEs.MethodsThe uni-irAE, multi-irAEs, and non-irAE were identified based on National Comprehensive Cancer Network (NCCN) guidelines. ICI efficacy for the disease control rate (DCR) and the objective response rate (ORR) was assessed based on the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. The association for the irAEs with progression-free survival (PFS) or overall survival (OS) was analyzed using the Kaplan–Meier method and Cox regression model. We also performed pairwise correlation analysis to identify co-occurrence patterns of multi-organ irAEs.ResultsA total of 288 patients including 175 non-irAE, 73 uni-irAE, and 40 multi-irAE patients were evaluated for their association with AGC outcome. The irAEs patients displayed higher DCR (78.8% vs. 67.4%, p=0.037) when compared with those of non-irAE patients, and both uni-irAE patients (82.2% vs. 67.4%, p=0.019) and multi-irAE patients (72.5% vs. 67.4%, p=0.534) showed higher DCR than that of non-irAE patients. The multivariate analyses revealed that multi-irAEs was an independent risk factor for PFS (hazard ratio [HR] of 0.63, 95% confidence interval [CI] 0.41~0.96, p=0.031) and OS (HR 0.47, 95% CI 0.29~0.76, p=0.002), whereas the survival association for uni-irAE was not obtained. The analysis of the co-occurrence patterns for multi-irAEs revealed that the thyroid, adrenal gland, heart, skin, and lung irAEs exhibited a high risk of co-occurrence of multi-irAEs. The multivariate Cox regression analysis for organ-specific irAEs revealed that patients experiencing thyroid, adrenal gland, and skin irAEs had favorable survival outcomes compared with those without these irAEs.ConclusionMulti-irAEs and some organ-specific irAEs can be used as predictive indicators for ICI treatment efficacy in AGC patients. The thyroid, adrenal gland, heart, skin, and lung irAEs are often accompanied by multi-irAE occurrence.
Ionizing radiation improves skin bacterial dysbiosis in cutaneous T-cell lymphoma
Authors: Chrisman Lauren P. , Pang Yanzhen , Hooper Madeline J. , Rajeev-Kumar Greeshma , Nguyen William Q. , Green Stefan J. , Seed Patrick C. , Liang Hua , Mittal Bharat B. , Hasan Yasmin , Guitart Joan , Weichselbaum Ralph R. , Burns Michael B. , Zhou Xiaolong A. 
Published: December 2024

IntroductionCutaneous T-cell lymphoma (CTCL) is closely associated with the host microbiome. While recent evidence suggests that shifts in specific bacterial taxa are associated with response to UV-B, a form of non-ionizing radiation, the impact of ionizing radiation (IR) has not been investigated.Methods16S rRNA and tuf gene amplicon sequencing were performed on DNA extracted from swabs of lesional/non-lesional skin of 12 CTCL patients before/after TSEBT or local IR and from 25 matched healthy controls (HC). Microbial diversity and taxonomic profiles were analyzed.ResultsRadiation exposure increased CTCL skin α-diversity to levels approximating HC. TSEBT appeared to carry the greatest effect compared to local IR. Both α and β-diversity differed significantly post versus pre-IR for TSEBT, but not for local IR. IR was associated with decreases in known pathogenic bacteria such as Streptococcus and S. aureus and increases in healthy commensal bacteria such as Anaerococcus, Bifidobacterium and commensal staphylococci including S. pettenkoferi. Substantially more taxa shifts were seen with TSEBT versus local IR.DiscussionIR not only eliminates CTCL lesions via induction of apoptosis, but also facilitates skin barrier restoration and recolonization of bacterial taxa associated with a healthy skin microbiome. Local IR does not have as strong an effect on the skin microbiome as TSEBT. As skin microbiota act as immunomodulators with local and potentially systemic influence, TSEBT may also improve CTCL lesions via global effects on the skin microbiome. Future larger-scale studies are required to fully elucidate the relationship between cutaneous microbes and IR treatment in CTCL.
Comparative efficacy of Vector Guard® to Olyset® Plus insecticide-treated nets against strongly pyrethroid-resistant Anopheles arabiensis in experimental huts in Tanzania
Authors: Machange Jane Johnson , Mbuba Emmanuel , Irish Seth R. , Swai Johnson Kyeba , Ntabaliba Watson , Makungwa Noely Otto , Ngonyani Safina , Mpelepele Ahmadi Bakari , Kibondo Ummi Abdul , Odufuwa Olukayode G. , Moore Sarah Jane 
Published: December 2024

IntroductionThe resistance of malaria vectors to pyrethroids has compromised the efficacy of pyrethroid insecticide-treated nets (ITNs). In response, ITNs with pyrethroids and piperonyl butoxide (PBO) synergists were developed to overcome metabolic pyrethroid resistance mechanisms. One such net is Vector Guard®. To demonstrate its potential efficacy for public health use, a comparative efficacy study was conducted to evaluate Vector Guard® relative to Olyset® Plus (a pyrethroid–PBO ITN proven to reduce malaria transmission more effectively than pyrethroid ITNs) and Royal® Sentry 2.0 (a pyrethroid-only ITN included to demonstrate the added benefit of PBO) in experimental huts in Tanzania.MethodsAn experimental hut trial using two blocks of a 7 × 7 Latin square design was conducted over seven rounds (49 experimental nights). Treatments were rotated at the end of each round, and volunteers were rotated nightly within one block. Both unwashed and 20× washed nets of each type were evaluated, alongside an untreated net used as a negative control. The primary endpoint was the proportion of Anopheles arabiensis that died within 24 h, and the secondary endpoint was the proportion of blood feeding. Data were analyzed using binomial logistic regression with fixed effects using a 7% non-inferiority margin.ResultsThe pooled results showed that Vector Guard® was non-inferior and was superior to Olyset® Plus, with higher mortality for Vector Guard® [28% vs. 18%; odds ratio (OR) = 1.93, 95%CI = 1.81–2.06]. Both pyrethroid–PBO nets were superior to Royal Sentry® 2.0 (p &lt; 0.001) in terms of mosquito mortality. For the secondary blood feeding endpoint, Vector Guard® was also found to be non-inferior to Olyset® Plus (0.6% vs. 0.2%; OR = 2.37, 95%CI = 1.77–3.17). Vector Guard® showed similar efficacy to Royal Sentry® 2.0 in reducing the proportion of mosquito blood feeding (0.6% vs. 0.6%; OR = 0.85, 95%CI = 0.68–1.07, p = 0.161).ConclusionVector Guard® demonstrated superior mosquito mortality compared with both Olyset® Plus and Royal Sentry® 2.0, indicating that Vector Guard® is another promising pyrethroid–PBO ITN for the control of resistant malaria vectors. The addition of Vector Guard® to the class of pyrethroid–PBO ITNs will enable malaria control programs to select cost-effective ITNs, improving access to effective protection from malaria transmitted by resistant vectors.
Electrotherapy as treatment for chemotherapy-induced peripheral neuropathy — a randomized controlled trial
Authors: Sassmann Robert , Gampenrieder Simon Peter , Rieder Florian , Johansson Tim , Rinnerthaler Gabriel , Castagnaviz Vanessa , Lampl Kathrin , Herfert Jürgen , Kienberger Yvonne Theres , Flamm Maria , Schaffler-Schaden Dagmar , Greil Richard 
Published: December 2024

BackgroundElectrotherapy has been investigated in chronic pain and diabetic peripheral neuropathy, however prospective trials in patients with chemotherapy-induced peripheral neuropathy (CIPN) are scarce.MethodsFifty-one patients with CIPN ≥ grade 1 subsequent to receiving platinum- and/or taxane-based chemotherapy types were randomized to 8 weeks of high tone external muscle stimulation (HTEMS) or transcutaneous electrical nerve stimulation (TENS). The primary outcome were changes in the EORTC-QLQ-CIPN20 questionnaire. Secondary outcomes included clinical examinations, a classification of CIPN according to CTCAE v 4 and the EORTC-QLQ-C30 questionnaire. A control group (n = 17) receiving no intervention was recruited retrospectively.ResultsThe EORTC-QLQ-CIPN20 sensory and motor scales improved in both intervention groups (TENS: −12.3pts and − 8.2pts; HTEMS: −14.7pts and − 8.2pts) with no significant changes in the control group −3.3pts; −2.8pts. The changes in the sensory scale differed significantly between the HTEMS and the control group. In the EORTC-QLQ-C30 questionnaire, there was a significant improvement for physical functioning in the HTEMS group only (+7.9pts) with no between group differences. CIPN classification according to CTCAE v4 improved significantly in both intervention groups.ConclusionHome-based electrotherapy with HTEMS or TENS were successful in improving CIPN-related sensory impairment and could therefore provide a powerful treatment for this side-effect of chemotherapy.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03978585
Mapping the research landscape of microRNAs in pain: a comprehensive bibliometric analysis
Authors: Wang Huaiming , Li Qin , Zou Jiang , Shu Jinjun , Zhang Aimin , Zhang Hongwei , Zhao Qi , Liu Shunxin , Chen Chan , Chen Guo 
Published: December 2024

Background and objectivesMicroRNAs (miRNAs) have demonstrated significant potential in pain medicine research, including mechanisms, diagnosis, and therapy. However, no relative bibliometric analysis has been performed to summarize the progress in this area quantitatively.MethodsLiterature was retrieved from the Web of Science Core Collection online database. A total of 1,295 papers were retrieved between January 1, 2000 and September 21, 2023 and underwent visualization and analysis using R software [Library [bibliometrix] and biblioshiny packages], VOSviewer (version 1.6.18), CiteSpace software (version 6.2.R4), and the bibliometrics website (http://bibliometric.com).ResultsPublications in this field have increased annually since 2000, demonstrating growing research interest. China emerged as the most productive country, followed by the United States and Germany. Keyword analysis identified “expression,” “neuropathic pain,” and “microRNAs” as the most relevant keywords. Extensive collaboration among countries and institutions was also observed.ConclusionThe bibliometric analysis revealed a rapid growth of publications related to miRNAs and pain in the past 2 decades. Keywords analysis indicates that “expression,” “neuropathic pain,” and “microRNA” are the most frequently used words in this research field. However, more robust and globally recognized basic studies and clinical trials from prestigious journals are required.
The global, regional, and national alcohol-related colorectal cancer burden and forecasted trends: results from the global burden of disease study 2021
Authors: Yao Jinfeng , Chen Guo 
Published: December 2024

BackgroundThe mortality of colorectal cancer (CRC) is increasing year by year and poses a significant global health burden. Many studies have demonstrated that alcohol consumption is an important risk factor for CRC and is closely associated with malignant metastasis in CRC patients, which in turn leads to a poor prognosis.MethodsThis study aimed to quantify the global, regional, and national burden of alcohol-related CRC between 1990 and 2021. First, numbers and age-standardized rates of deaths and disability-adjusted life years (DALYs) for alcohol-related CRC in 2021 were analyzed at different levels. Temporal trends in the burden of disease from 1990 to 2021 were analyzed through linear regression models. Finally, both Age-Period-Cohort (APC) models and Bayesian Age-Period-Cohort (BAPC) models were utilized to project the future burden of the disease for 2022–2046.ResultsThe global burden of disease for alcohol-related CRC is higher in 2021 compared to 1990. Male and older age groups are at high risk. Disease burden varies very much between Sociodemographic Index (SDI) regions, Global Burden of Disease (GBD) regions and countries. From 1990 to 2021, the number of cases increased, but the Age-Standardized Rate (ASR) decreased. The trends in disease burden predicted by the two models for 2022–2046 were not consistent.ConclusionThis study describes the burden of disease in alcohol-related CRC and emphasizes that alcohol is a non-negligible risk factor for CRC. In order to mitigate harm, we need to strengthen disease surveillance, early prevention, timely detection, and improved treatment measures, with different approaches and responses for different regions.
Dosimetric investigation of couch rotation angles in non-coplanar VMAT plans for lung cancer SBRT
Authors: Ye Weiqiang , Wang Housheng , Wei Zhenzhen , Zhang Wei , Yu Chaojun , Zhang Dawei , Su Shida , Qin Wen , Hu Kai , Li Bo 
Published: December 2024

BackgroundThis study aimed to investigate the effect of couch rotation angles on non-coplanar volumetric modulated arc therapy (ncVMAT) plan for stereotactic body radiotherapy (SBRT) in lung cancer patients and to evaluate the feasibility of clinically applying ncVMAT for SBRT.MethodsTwenty-four lung cancer patients with a single lesion eligible for SBRT were enrolled in the study. Seven dual partial-arc VMAT plans with varying couch angles were designed for every patient. These plans utilized two partial arcs, with the same first arc set at a fixed 0° couch angle in all plans. The second arc’s couch angle varies at 15° intervals, ranging from 0° to 90°. The plans are designated as C0, NC15, NC30, NC45, NC60, NC75, and NC90, respectively. Plan evaluation included assessment of the maximum dose (Dmax), the mean dose (Dmean), homogeneity index (HI), conformity index (CI), and the ratio of the 50% isodose volume to the planning target volume (R50%). Dosimetric parameters for organs at risk such as the ipsilateral lung, contralateral lung, bilateral lungs, esophagus, trachea, chest wall, heart, and spinal cord were analyzed. Additionally, plan complexity-related metrics included modulation degree (MD), delivery time (DT), and monitor unit (MU) were assessed.ResultsAs the couch rotation angle increased, parameters such as Dmax, Dmean, HI, CI, R50%, V20Gy, V25.75Gy and V30Gy of the ipsilateral lung and bilateral lungs, V10Gy of the contralateral lung and Dmean of the chest wall varied, while MD, MU, and DT increased. Compared to C0, the Dmax, Dmean, and HI of the planning target volume (PTV) decreased from 6728.35 ± 209.56cGy, 5743.04 ± 93.45cGy, and 0.281 ± 0.032 to 6500.48 ± 225.26cGy, 5654.81 ± 109.23cGy, and 0.245 ± 0.031, respectively, when the couch was rotated to 90°. The CI increased from 0.859 ± 0.031 to 0.876 ± 0.024. Decreases in R50% were 1.4%, 4.9%, 9%, 13.5%, 16.8%, and 18.4% for NC15, NC30, NC45, NC60, NC75, and NC90, respectively.ConclusionsIn the treatment of lung cancer using SBRT, ncVMAT plans demonstrate superior dose distribution and deliver lower doses to certain OARs compared to cVMAT plans. This advantage becomes more pronounced with increasing couch rotation angles. Our study offers theoretical support for the preferential use of ncVMAT plans in lung cancer SBRT and provides empirical evidence to guide the selection of optimal couch rotation angles.
Carthamus tinctorius L. protects cerebral ischemia/reperfusion injury via arachidonic acid/p53-mediated apoptosis axis
Authors: Chen Junren , Wu Liujun , Xie Xiaofang , Peng Cheng 
Published: December 2024

IntroductionStroke is a debilitating disease and the second leading cause of death worldwide, of which ischemic stroke is the dominant type. Carthamus tinctorius L., also known as safflower, has been used to treat cerebrovascular diseases, especially ischemic stroke in many Asian countries. However, the underlying mechanisms of safflower in preventing ischemic stroke remains elusive. This study aims to elucidate the potential of safflower as a drug candidate for the prevention of ischemic stroke and to delineate its protective effects and potential mechanisms in a rat model of cerebral ischemia-reperfusion injury (CI/RI).MethodsThe aqueous extract of safflower (AESF) was verified using HPLC-UV, HPLC-MS, and TLC. The inhibitory effect of AESF on platelet aggregation was detected in vitro and in zebrafish and mice. A CI/RI model in rats was established by middle cerebral artery occlusion and reperfusion to study the protective effect of AESF on ischemic stroke. 2,3,5-triphenyltetrazolium chloride, hematoxylin and eosin, and Nissl’s staining were employed to evaluate the pathological changes of brain tissue. In addition, metabolomics, ELISA, and Western blot were used to uncover the molecular alteration induced by AESF.ResultsAESF significantly inhibited platelet aggregation in vitro, reduced the thrombogenesis in zebrafish, and prolonged clotting time in mice. In addition, AESF alleviated neurological dysfunction, cerebral oedema, cerebral infarct size, cerebral histopathological damage induced by ischemia-reperfusion, improved neuronal survival, increased serum levels of SOD and CAT, and decreased levels of iNOS and NO. Metabolomics revealed that AESF attenuated the metabolic disturbances in brain caused by I/R injury via regulating 38 metabolites particularly related to the arachidonic acid (AA) metabolism. Moreover, AESF elevated the serum levels of 6-keto-PGF1α, a pivotal metabolite of AA, downregulated the protein expression of p53, Bax, cleaved caspase-9, cleaved caspase-3, and cleaved caspase-8, and upregulated that of Bcl-2.ConclusionAESF mitigated CI/RI through preventing platelet aggregation, alleviating oxidative stress, and suppressing apoptosis partially via modulating AA metabolism/p53-mediated apoptosis axis.
Emodin induced hepatic steatosis in BALb/c mice by modulating the gut microbiota composition and fatty acid metabolism
Authors: Xia Xinhua , He Xueling , Huang Jinzhou , Hou Xuyang , Lin Chen , Liu Yaxiong , Liu Mei 
Published: December 2024

IntroductionThe aim of this study is to examine the physiological effects of emodin on intestinal microorganisms and the liver in the BALb/c mice.Method and ResultsFollowing an 8-week administration of emodin at doses of 25, 50, and 100 mg/kg/day,pathological analyses revealed that emodin significantly reduced the colon length, induced colonic crypt inflammation,diminished the colonic mucus layer,and decreased the fluorescence intensity of colonic tight junction proteins ZO-1 and Occludin. Concurrently, 16S rDNA gene sequencing corroborated that emodin altered the diversity and composition of the intestinal microbiota by increasing the Firmicutes to Bacteroides ratio. Simultaneously, the non-targeted metabolomics analyses exhibited significant alternations in both short chain fatty acids and free fatty acids between the emodin-treated and the normal groups, indicating emodin-induced disturbance in intestinal metabolic disorder. Furthermore, emodin exhibited a significant elevation in LPS levels in colon, serum and liver as well an marked increase in the levels of TC, TG, AST, and ALT in serum. Additionally, histological examination employing by HE and oil-red O staining furtherly verified that the administration of varying doses emodin induced hepatic inflammation and lipid accumulation. Whereas qRT-PCR and Western blot analyses demonstrated that the administering of varying doses of emodin upregulated the mRNA levels of TNF-α, IL-1β, IL-6, and IL-18 as well as the expression of TLR4, Myd88, and P-65. Following the combined administration of probiotics, the high-dose emodin did not significantly influence ALT and AST levels in mice. However, the faeces of the high-dose emodin transplanted in mice and induced a significant increase in AST levels and in the relative abundance of Firmicutes and Proteobacteria.DiscussionThese findings further corroborate that emodin induces liver injury via the intestinal dysfunction. These findings suggested that emodin may disrupt intestinal microbiota and resulted in significant alternations in endogenous metabolites in mice, thereby facilitating the entry of LPS and FFAs into the liver, potentially leading to hepatic injury.
Effects of exercise on bone mass and bone metabolism in adolescents: a systematic review and meta-analysis
Authors: Zhang Wenhua , Wang Xiaoqiang , Liu Yurong , He Qiang , Ding Qixin , Mei Jingqi , Li Xun 
Published: December 2024

ObjectiveMeta-analysis was used to evaluate the effects of an exercise intervention on bone mineral content (BMC), bone mineral density (BMD), and bone metabolism in adolescents.MethodsA systematic search of PubMed, Embase, Cochrane Library, and Web of Science for RCTs on “exercise, adolescents, BMD, bone metabolism” up to 10 September 2024. Included RCTs focused on effects of exercise on BMC, BMD, and bone metabolism in 10–19 years old, with physical activity as exercise group and daily living/primal exercise as control group. Outcome metrics included lumbar spine, femoral neck, whole body BMC and BMD, bone alkaline phosphatase (BALP), procollagen type 1N-terminal propeptide (PINP), osteocalcin (OC), and type I collagen carboxy-terminal peptide (CTX). Exclusion criteria included duplicates, non-RCTs, non-adolescent studies, and non-compliance with indicators. Meta-analyses were performed using RevMan 5.4, and quality assessed by Cochrane’s tool. Effect sizes were estimated using standardized mean differences (SMDs) and 95% confidence intervals (CIs), and heterogeneity was assessed using the I2 statistic to determine fixed or random effects models.ResultsFifteen articles with a total of 723 subjects were included. The meta-analysis showed that, compared to the control group, (i) exercise was effective in increasing adolescents’ overall BMC (SMD = 0.16, 95% CI: 0.06–0.27, p = 0.003) and BMD (SMD = 0.26, 95% CI: 0.13–0.40, p = 0.0001). (ii) Subgroup analyses showed that exercise significantly increased adolescents’ lumbar spine BMC (SMD = 0.17, 95% CI: 0.01–0.34, p = 0.04), femoral neck BMC (SMD = 0.23, 95% CI: 0.05–0.42, p = 0.01), lumbar spine BMD (SMD = 0.34, 95% CI: 0.12–0.56, p = 0.003) and femoral neck BMD (SMD = 0.31, 95% CI: 0.09–0.53, p = 0.007), whereas there was no statistically significant effect on whole body BMC and BMD (p &gt; 0.05). (iii) Exercise increased BALP, and decreased PINP, OC and CTX in adolescents. but none of the differences between the exercise groups and the control group were significant (p &gt; 0.05).ConclusionExercise is effective in improving overall BMC and BMD in adolescents and elevating BMC and BMD of the lumbar spine and femoral neck. Due to the limitation of the number and quality of the included studies, the above conclusions are yet to be validated by more high-quality empirical studies.Systematic Review Registrationhttps://www.crd.york.ac.uk/, identifier CRD42024593399