bluuebunny/crossref_metadata_2025_split huggingface dataset:
Somatic mutational landscape reveals mutational signatures and significantly mutated genes of cancer immunotherapeutic outcome and sex disparities
Authors: Li Yuting , Wang Qinghua , Gao Xiaopan , Zheng Jinyang , Zhang Wenjing , Ren Yanfeng , Shen Wei , Su Wei , Lu Ping 
Published: November 2024

BackgroundCurrently developed molecular markers can predict the effectiveness of cancer immunotherapy and screen beneficiaries to some extent, but they are not stable enough. Therefore, there is an urgent need for discovering novel biomarkers. At the same time, sex factor plays a vital role in the response to immunotherapy, so it is particularly important to identify sex-related molecular indicators.MethodsWe integrated a pan-cancer cohort consisting of 2348 cancer patients who received immune checkpoint inhibitors and targeted sequencing. Using somatic mutation profiles, we identified mutational signatures, molecular subtypes, and frequently mutated genes, and analyzed their relationships with immunotherapeutic outcomes. We also explored sex disparities of determined biomarkers in response to treatments.ResultsWe found that male patients exhibited better immunotherapy outcomes and higher tumor mutational burden. A total of seven mutational signatures were identified, among which signatures 1 and 3 were associated with worse immunotherapy outcomes, while signatures 2 and 6 correlated with better outcomes. Gender-based analysis revealed that mutational signature 1 continued to show a worse immunotherapy outcome in female patients, whereas signature 6 demonstrated a better outcome in male patients. Based on mutational activities, we identified four potential molecular subtypes with gender differences and relevance to treatment outcomes. PI3K-AKT, RAS signaling pathways, and 68 significantly mutated genes were identified to be associated with immunotherapy outcomes, with nine genes (i.e., ATM, ATRX, DOT1L, EP300, EPHB1, NOTCH1, PBRM1, RBM10, and SETD2) exhibiting gender differences. Finally, we discovered co-mutated gene pairs and TP53 p.R282W mutations related to treatment outcomes, highlighting their gender-specific differences.ConclusionThis study identified several molecular biomarkers related to cancer immunotherapy outcomes in terms of mutational signatures, molecular subtypes, and mutated genes, and explored their gender-relatedness in order to provide clues and basis for clinical treatment efficacy evaluation and patient selection.
Efficacy and safety analysis of neoadjuvant chemotherapy combined with immunotherapy in patients with muscle-invasive bladder cancer
Authors: Yu Yanhang , Zhang Chuanao , Chen Hao , Zhang Jianglei , Ouyang Jun , Zhang Zhiyu 
Published: November 2024

IntroductionThis study examined the efficacy and safety of neoadjuvant chemotherapy combined with immunotherapy in patients with muscle-invasive bladder cancer (MIBC).MethodsThis retrospective cohort study included patients diagnosed with MIBC at the First Affiliated Hospital of Soochow University between January 1, 2020, and December 31, 2023, assigned to either chemotherapy (gemcitabine with cisplatin) or combination (chemotherapy plus toripalimab or tislelizumab) groups based on the neoadjuvant treatment regimen. Key metrics, including pathological downstaging rate (PDR), pathological complete response rate (PCRR), and incidence and severity of adverse events (AEs), were compared between groups.ResultsThis study included 53 patients (mean age: 67.21 years). In the combination group, 14 patients (51.85%) achieved pathological complete remission (ypT0), and seven (25.93%) achieved partial remission (ypT1), resulting in a PDR and PCRR of 77.78 and 51.85%, respectively. In the chemotherapy group, six patients (23.08%) achieved complete remission, and five (19.23%) achieved partial remission, resulting in a PDR and PCRR of 42.31 and 23.08%, respectively. Differences between groups were statistically significant (p &lt; 0.05). There were no significant differences in pathological downstaging or complete remission rates among subgroups in the combination group (p &gt; 0.05). No serious allergic reactions or fatal AEs were detected in either group, with no grade 4 AEs. Grade 3 AE rates were 22.22 and 20.83% in the combination and chemotherapy groups, respectively, although non-significant (p &gt; 0.05).ConclusionNeoadjuvant chemotherapy combined with immunotherapy had enhanced efficacy and manageable safety in patients with MIBC, suggesting its potential for integration into clinical practice.
Behavioral response of Aedes aegypti (Diptera: Culicidae) to essential oils of Cymbopogon nardus (L.) Eucalyptus camaldulensis (Dehnh) and their blend in Y-maze olfactometer
Authors: Wangrawa Dimitri Wendgida , Chandrasegaran Karthikeyan , Upshur Forde , Borovsky Dov , Sharakhov Igor V. , Vinauger Clement , Badolo Athanase , Sanon Antoine , Lahondère Chloé 
Published: November 2024

BackgroundAedes aegypti vectors several important arboviruses including dengue and yellow fever. This vector mosquito is controlled mainly by using synthetic insecticides and repellents. Overusing these insecticides causes mosquito resistance, harms the environment, and affects human health. This report reevaluates the repellent activities of Cymbopogon nardus, Eucalyptus camaldulensis essential oils (EOs), and their mixtures against laboratory-reared adult Ae. aegypti.MethodsThe chemical composition of C. nardus, E. camaldulensis EOs, and their 1:1 combination was identified by gas chromatography-mass spectrometry (GC-MS). We evaluated the repellent activities of these oils against Ae. aegypti using a Y-maze olfactometer. The preference index (PI) was evaluated and compared with the binary data obtained from the olfactometer assay with samples that did not contain EOs (control) using an Exact Binomial test (α= 0.05)ResultsSeveral monoterpenes and sesquiterpene compounds were found in EOs and their mixture. The EOs of E. camaldulensis and the mixture of the two oils showed a repellent activity of 50%, whereas C. nardus was less active and attracted mosquitoes at 1 ppm.ConclusionWe show that EOs from C. nardus and E. camaldulensis contain compounds that repel Ae. aegypti. Future studies will identify specific compounds with the highest repellent activities and use them to formulate in the future a potent repellent against Ae. aegypti for human protection.
The archaeal and bacterial community structure in composted cow manures is defined by the original populations: a shotgun metagenomic approach
Authors: Romero-Yahuitl Vanessa , Zarco-González Karla Estephanía , Toriz-Nava Ana Lilia , Hernández Mauricio , Velázquez-Fernández Jesús Bernardino , Navarro-Noya Yendi E. , Luna-Guido Marco , Dendooven Luc 
Published: November 2024

IntroductionOrganic wastes are composted to increase their plant nutritional value, but little is known about how this might alter the bacterial and archaeal community structure and their genes.MethodsCow manure was collected from three local small-scale farmers and composted under controlled conditions, while the bacterial and archaeal communities were determined using shotgun metagenomics at the onset and after 74 days of composting.ResultsThe bacterial, archaeal, methanogen, methanotrophs, methylotroph, and nitrifying community structures and their genes were affected by composting for 74 days, but the original composition of these communities determined the changes. Most of these archaeal and bacterial groups showed considerable variation after composting and between the cow manures. However, the differences in the relative abundance of their genes were much smaller compared to those of the archaeal or bacterial groups.DiscussionIt was found that composting of different cow manures did not result in similar bacterial or archaeal communities, and the changes that were found after 74 days were defined by the original populations. However, more research is necessary to determine if other composting conditions will give the same results.
Fecal microbiota transplantation alleviates cognitive impairment by improving gut microbiome composition and barrier function in male rats of traumatic brain injury following gas explosion
Authors: Dong Xinwen , Su Yaguang , Luo Zheng , Li Cuiying , Gao Jie , Han Xiaofeng , Yao Sanqiao , Wu Weidong , Tian Linqiang , Bai Yichun , Wang Guizhi , Ren Wenjie 
Published: November 2024

BackgroundDysbiosis of gut microbiota (GM) is intricately linked with cognitive impairment and the incidence of traumatic brain injury (TBI) in both animal models and human subjects. However, there is limited understanding of the impact and mechanisms of fecal microbiota transplantation (FMT) on brain and gut barrier function in the treatment of TBI induced by gas explosion (GE).MethodsWe have employed FMT technology to establish models of gut microbiota dysbiosis in male rats, and subsequently conducted non-targeted metabolomics and microbiota diversity analysis to explore the bacteria with potential functional roles.ResultsHematoxylin–eosin and transmission electron microscopy revealed that GE induced significant pathological damage and inflammation responses, as well as varying degrees of mitochondrial impairment in neuronal cells in the brains of rats, which was associated with cognitive decline. Furthermore, GE markedly elevated the levels of regulatory T cell (Tregs)-related factors interleukin-10, programmed death 1, and fork head box protein P3 in the brains of rats. Similar changes in these indicators were also observed in the colon; however, these alterations were reversed upon transfer of normal flora into the GE-exposed rats. Combined microbiome and metabolome analysis indicated up-regulation of Clostridium_T and Allobaculum, along with activation of fatty acid biosynthesis after FMT. Correlation network analysis indirectly suggested a causal relationship between FMT and alleviation of GE-induced TBI. FMT improved intestinal structure and up-regulated expression of tight junction proteins Claudin-1, Occludin, and ZO-1, potentially contributing to its protective effects on both brain and gut.ConclusionTransplantation of gut microbiota from healthy rats significantly enhanced cognitive function in male rats with traumatic brain injury caused by a gas explosion, through the modulation of gut microbiome composition and the improvement of both gut and brain barrier integrity via the gut-brain axis. These findings may offer a scientific foundation for potential clinical interventions targeting gas explosion-induced TBI using FMT.
“Living with” CACNA1A-related hemiplegic migraine, a disease concept model
Authors: Schaare Donna , Allison Kendra , Skorge Kara , Fox Pangkong , Lusk Laina , Sarasua Sara M. , Helbig Ingo , Boccuto Luigi 
Published: November 2024

IntroductionCACNA1A-related Hemiplegic Migraine (HM) is a rare neurological disorder distinguished by paroxysmal episodes of hemiparesis/hemiplegia with and without headache. Clinical features have been widely characterized, yet the impacts of the paroxysmal events on the patient and caregiver have not been thoroughly explored. Disease concept models are formal frameworks used to describe the lived experiences of patients and their families, offering a source for surrogate endpoints for clinical trials.MethodsWe completed 13 semi-structured interviews with caregivers of 12 individuals diagnosed with CACNA1A-related HM. We methodically coded themes, grouping concepts into three domains. We measured the occurrence of concepts throughout all interviews and subgroups stratified by age categories.ResultsOver 11 h of interviews yielded 2,018 references to 27 distinct concepts. Established symptoms such as seizures (87 references; including status epilepticus 27 references), hemiparesis/hemiplegia (24 references), and unconsciousness (17 references) were referenced, as well as previously underreported symptoms such as apneic episodes (32 references), lost ability to eat (13 references), and vascular access challenges (10 references). The symptom impacts were largely medical (294 references), followed by health (101 references), emotional (36 references), daily living (28 references), and social (26 references). Caregiver impacts were the most referenced domain (995 references), with the pivotal effects seen in caregiver requirements (355 references), emotional (245 references), HM treatments (179 references), daily living (148 references), and health support (135 references).DiscussionCACNA1A-related HM is a complex disorder defined by serious paroxysmal events that affects a broad range of social and clinical domains. We systematically classified symptoms and impacts from HM episodes, creating a disease concept model to help develop surrogate endpoints for future clinical trials, and identified two opportunities to improve patient management, including a written emergency protocol and a transition plan for adolescents approaching adulthood.
VCAN in the extracellular matrix drives glioma recurrence by enhancing cell proliferation and migration
Authors: Wei Ruolun , Xie Haoyun , Zhou Yukun , Chen Xuhao , Zhang Liwei , Bui Brandon , Liu Xianzhi 
Published: November 2024

IntroductionGliomas are the most prevalent primary malignant intracranial tumors, characterized by high rates of therapy resistance, recurrence, and mortality. A major factor contributing to the poor prognosis of gliomas is their ability to diffusely infiltrate surrounding and even distant brain tissues, rendering complete total resection almost impossible and leading to frequent recurrences. The extracellular matrix (ECM) plays a key role in the tumor microenvironment and may significantly influence glioma progression, recurrence, and therapeutic response.MethodsIn this study, we first identified the ECM and the Versican (VCAN), a key ECM protein, as critical contributors to glioma recurrence through a comprehensive analysis of transcriptomic data comparing recurrent and primary gliomas. Using single-cell sequencing, we revealed heterogeneous distribution patterns and extensive intercellular communication among ECM components. External sequencing and immunohistochemical (IHC) staining further validated that VCAN is significantly upregulated in recurrent gliomas and is associated with poor patient outcomes.ResultsFunctional assays conducted in glioma cell lines overexpressing VCAN demonstrated that VCAN promotes cell proliferation and migration via the PI3K/Akt/AP-1 signaling pathway. Furthermore, inhibiting the PI3K/Akt pathway effectively blocked VCAN-mediated glioma progression.ConclusionThese findings provide valuable insights into the mechanisms underlying glioma recurrence and suggest that targeting both VCAN and the PI3K/Akt pathway could represent a promising therapeutic strategy for managing recurrent gliomas.
Waist-to-hip ratio and nonalcoholic fatty liver disease: a clinical observational and Mendelian randomization analysis
Authors: Xie Weining , Hong Yan , Chen Xinrong , Wang Shujuan , Zhang Fan , Chi Xiaoling 
Published: November 2024

BackgroundObesity often coincides with non-alcoholic fatty liver disease (NAFLD), yet a significant portion of NAFLD patients exhibit normal body mass index (BMI) but have abdominal obesity. Recognizing this discrepancy, we aimed to delve deeper into this phenomenon through observational studies coupled with two-sample Mendelian randomization (MR) analysis, with waist-to-hip ratio (WHR) serving as the indicator for abdominal obesity. Our objective was to ascertain whether WHR correlates with an increased risk of NAFLD development.MethodsThis study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 to examine the association between WHR and NAFLD through weighted multivariate logistic regression models. On this basis, subgroup analyses were performed to further explore the correlation between WHR and NAFLD. Subsequently, a two-sample MR analysis was conducted using genome-wide association studies (GWAS) data to investigate the potential causal relationship between WHR and NAFLD. Sensitivity analyses were also employed to ensure the robustness of our findings.ResultsA total of 3,732 eligible participants were included in the analysis. Weighted multivariable-adjusted logistic regression models revealed a positive association between WHR and the risk of NAFLD (Q2vsQ1: OR = 1.94 [95% CI: 1.55–2.44]; Q3vsQ1: OR = 2.08 [95% CI: 1.51–2.85]; Q4vsQ1: OR = 3.70 [95% CI: 2.13–6.43], p &lt; 0.05). The results of the subgroup analysis suggested that there was an interaction in the correlation between WHR and NAFLD in normal weight, overweight, and obese populations (p &lt; 0.05). The RCS curves indicated that there was a nonlinear relationship between WHR and NAFLD in populations with BMI in the normal versus obese categories. Furthermore, MR analysis provided additional support for the causal relationship between WHR and NAFLD. Using inverse variance weighting (IVW), the MR analysis yielded an OR of 2.062 (95% CI: 1.680–2.531, p&lt;0.05). Consistent results were obtained with the other four MR methods, all supporting the same direction of causality. Sensitivity analyses were performed to assess the robustness of the findings (p &gt; 0.5), further reinforcing the reliability of the observed associations.ConclusionWHR elevation heightens the susceptibility to NAFLD.
The impact of tumor burden score on prognosis in patients after radical resection of hepatocellular carcinoma: a single-center retrospective study
Authors: Huang Junzhang , Zhou Ying , Wei Suosu , Tang Yuntian , Zhang Qiuhuan , Tang Yi , Huang Wei , Mo Chongde , Dong Xiaofeng , Yang Jianrong 
Published: November 2024

PurposeThis study examines the relationship between tumor burden score (TBS) and survival and recurrence following radical resection of hepatocellular carcinoma through a cohort study conducted in the Guangxi population of China.MethodsThis cohort study eventually recruited 576 HCC patients undergoing radical resection of HCC in the People’s Hospital of Guangxi Zhuang Autonomous Region during 2013–2022. After determining the best threshold TBS, all cases were grouped to evaluate the relationship between TBS versus overall survival (OS) and cumulative recurrence. Using X-Tile software, the best threshold TBS to judge patient prognostic outcome following radical resection of HCC was 10.77.ResultsKaplan–Meier curve analysis revealed that patients with high TBS showed considerably decreased OS relative to the control group, accompanied by an increased recurrence rate. According to multivariate Cox proportional regression, the patients with high TBS were associated with poorer OS (HR = 2.56, 95% CI 1.64–3.99, P &lt; 0.001) and recurrence-free survival (RFS) (HR = 1.55, 95% CI 1.02–2.35, P &lt; 0.001).ConclusionIn patients undergoing radical resection for HCC, higher TBS was significantly related to shorter OS and RFS.
Contribution of fracture healing in paediatric DMP zone fracture patients using the pry lever technique
Authors: Zhang Jingyuan , Cao Hong 
Published: November 2024

BackgroundThis study describes the efficacy of applying the prying lever technique to distal radial metaphyseal symphysis diaphysis joining region (DMP) fractures in children, and reports that the technique has an ameliorative effect on the phenomenon of delayed healing and non-union that occurs after surgery for fractures in the DMP region.MethodsThe medical records of 72 children with fractures in the DMP region, treated between December 2017 and December 2023, were retrospectively analyzed. The patients were randomly assigned to either the cut-and-displace group (n = 36) or the pry-and-lever group (n = 36). Both groups were monitored for time to fracture healing, incidence of delayed or non-union, radiologic outcomes, complications, and functional assessments using the EQ-5D, DASH, and VAS scales.ResultsThe follow-up period ranged from 3 to 5 years, with a mean of 26.5 months. After 6 months of follow-up, the incidence of delayed/non-union of fractures was 2.7% and 16.6% in the study and control groups, respectively, and the incidence of delayed healing was significant (P &lt; 0.05) in both groups. Additional manipulations or complications caused by delayed healing or non-union were also significantly less in the study group than in the control group. The EQ-5D scale was used to compare the level of surgical satisfaction between the two groups, and the study group had a higher level of satisfaction. Carpal function was significantly improved in both groups compared to the preoperative period, scored using the DASH scale (P &gt; 0.05). Postoperative pain level was scored using VAS (P &lt; 0.05).ConclusionThe prying lever technique has the advantages of low impact on periosteal blood supply, simple operation, and fast recovery, which makes it a worthwhile attempt of minimally invasive reduction of fractures in the DMP region in children.
Sex bias in prospective follow-up observational studies with drugs carried out in a southern region of Europe
Authors: Santomà Àlex , Jambrina Anna Maria , Perisé Adela , Armelles Mercè , Perisé Lluisa , Pareja Clara , Rams Neus , Rabanal Manel 
Published: November 2024

IntroductionThe impact of sex bias in medical research is a matter of significant relevance and importance especially in the modern age. Despite notable improvements in sex equity across various societal fields, disparities in sex representation persist within clinical and pharmacological research. The objective of this article is to investigate the sex bias within Prospective Follow-up Observational Studies with Drugs authorized by the Advisory Commission on Post-Authorization Studies with Medicines in Catalonia, a southern European region.MethodsA retrospective study that analyses data from final reports of Prospective Follow-up Observational Studies with Drugs authorized by the Advisory Commission on Post-Authorization Studies with Medicines in Catalonia from 2015 to 2021. Disease categories and specific diseases, obtained from the Global Data Exchange, were evaluated for sex bias, comparing female participation to female prevalence.ResultsThere were 1,06,399 participants, including 43,778 female participants (42.5%). A significant underrepresentation of females was observed across various disease categories. Notably, in 12 out of 19 categories (63.2%), a pronounced female underrepresentation (sex bias ≤ 0.05) was evident, particularly in the categories of HIV/AIDS and sexually transmitted infections (sex bias = −0.5659). Furthermore, 11 categories (57.9%) also demonstrated significant female underrepresentation, with the same notable categories, HIV/AIDS and sexually transmitted infections (sex bias = −0.4439). When examining specific diseases, significant female underrepresentation was observed in 13 out of 29 diseases (46.4%), especially in HIV (sex bias = −0.4781). The overall findings indicate that the degree of sex bias was notably less favorable for females in numerous disease categories and specific conditions.ConclusionOur study has demonstrated a significant sex bias within observational studies, mirroring patterns observed in clinical trials. Importantly, our findings highlight a pervasive underrepresentation of women across various disease categories and specific conditions. Despite efforts to promote both sexes inclusivity, our results emphasize the persistent challenges in achieving balanced sex representation in study populations. Furthermore, the absence of categorization of diseases based on male and female prevalence poses a significant challenge in accessing pertinent data, particularly concerning the sex distribution of specific diseases.