bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-derived Extracellular Vesicles-mediated Oxidative Stress Transfer Activates Glycometabolic Reprogramming of CAFs
Authors: Jiang Erhui , Li Xiang , Dou Xinyu , Xu Yuming , Shao Zhe , Shang Zhengjun 
Published: December 2024

Abstract

Background
Stressed by the adverse conditions of the tumor microenvironment (TME), hyperproliferation of tumor cells is accompanied by high production of reactive oxygen species (ROS). Tumor-derived extracellular vesicles (TEVs) exert a variety of biological functions in the interaction between the tumor cells and cancer-associated fibroblasts (CAFs). However, the intercellular transmission of ROS and its role in tumor-stroma communication remain unclear.
Method
The human gingival fibroblasts (HGFs), paracancerous normal fibroblasts (PNFs) and CAFs were isolated from the healthy gingival tissues of volunteers and six patients with OSCC. HGFs were treated with CAL27/SCC25 TEVs. In vitro, we assessed the level of autophagy and glycometabolism in PNFs/CAFs and HGFs/TEVs-treated HGFs by immunofluorescence and Western blot. Blockage or activation of autophagy was employed to investigate its effects on glycometabolism. Flow cytometry was used to detect whether TEVs play a crucial role in inducing fibroblast autophagy and glycolysis through ROS transfer. In vivo, xenograft models were established to validated the effect of TEVs.
Results
CAFs exhibited higher level in autophagy compared with PNFs. Treatment with autophagy inhibitors diminished autophagy-dependent glycometabolic reprogramming induced by TEVs, whereas activation of autophagy enhanced glycolysis in CAFs. Furthermore, ROS transferred by TEVs was confirmed to drive glycometabolic reprogramming through both autophagy-dependent mechanisms and the HIF-1α/PFKFB3 axis. In vivo, TEVs consistently promoted autophagy and glycometabolic reprogramming.
Conclusion
TEVs-induced intercellular transmission of ROS and the regulatory role of ROS-mediated autophagy in the glycometabolic reprogramming of CAFs, providing a novel rationale for the oxidative stress transfer model in tumor-stroma crosstalk.
A Heart Failure Classification Model from Radial Artery Pulse Wave Using LSTM Neural Networks
Authors: Lyu Yi , Huang Wen-Yue , Wu Hai-Mei , Hong Jing , Wang Yi-Qin , Yan Hai-Xia , Xu Jin 
Published: December 2024

Abstract

Background The pressing global health issue of heart failure (HF) demands innovative approaches for early detection. Non-invasive, rapid, and cost-effective deep learning (DL)-based techniques offer a promising avenue for addressing this challenge.
Methods A total of 462 participants were categorized into three groups: healthy, coronary artery disease (CAD), and heart failure (HF). Raw radial artery pulse wave data were collected from each participant, followed by preprocessing steps including denoising, normalization, and balancing. Subsequently, four deep learning (DL) algorithms were applied to the processed data: Long Short-Term Memory (LSTM), Convolutional Neural Network (CNN), Gated Recurrent Unit (GRU), and Bidirectional Long Short-Term Memory (Bi-LSTM).
Results LSTM achieved the highest classification performance, with an accuracy of 0.8587, precision of 0.87448, recall of 0.82164, F1-score of 0.83773, specificity of 0.92369, and AUC of 0.93365. Given its superior performance across all metrics, LSTM emerges as the preferred DL model for this study.
Conclusion By employing LSTM to analyze radial artery pulse wave, we can accurately distinguish between healthy individuals, patients with CAD, and those with HF. This simple, non-invasive, and cost-effective method presents a potential strategy for early detection of HF.
Global, regional, and national burdens of pancreatitis in children and adolescents aged 0–24 years from 1992 to 2021: a trend analysisbased on the Global Burden of Disease Study 2021
Authors: Deng Ying-han , Qiu Huabin , Huang Kangming , Huang Yanbin , Lian Fuming , Chen Yun , Chen Hongbin 
Published: December 2024

Abstract

Background:Younger onset of pancreatitis poses a significant public health challenge, this study aims to analyze the global burden of pancreatitis in young populations based on Global Burden of Disease 2021.
Methods:This study uses Incidence and Disability-adjusted life-years (DALYs) to assess the pancreatitis burden. Using Joinpoint modeling to assess the trend of the burden. Using Age-Period-Cohort (APC) modeling to assess age annual percentage changes as well as period and cohort relative risks. Using Norpred modeling to predict the burden through 2040.
Results:Globally, the incidence of pancreatitis among younger individuals is 9.16/100,000(95%UI 5.74 to 13.85) in 2021, AAPC 0.13 (95%CI 0.12-0.14); the DALYs is 6.36/100,000(95%UI 5.21-7.97) in 2021, AAPC -0.93 [95%CI (-1.01 to -0.85)]. Global incidence rates of pancreatitis have risen notably since 1999, and the overall burden of DALYs has declined over the 30 years. In the APC model, different age group experienced different risks. According to the Norpred predictive model, by 2040, the global incidence of pancreatitis among younger individuals is projected to reach 313,567 cases, with an rate of 9.07/100,000.
Conclusion:Globally, the incidence of pancreatitis in younger individuals has risen over the past three decades. Urgent policy interventions are needed to address healthcare inequities to alleviate this burden.
Dose-dependent effects of curcumin on 22Rv1 prostate cancer cell line
Authors: Tossetta Giovanni , Fantone Sonia , Busilacchi Elena Marinelli , Marzioni Daniela , Mazzucchelli Roberta 
Published: December 2024

Abstract

Background
Prostate cancer (PCa) is the second most frequent cancer type in male population over 66 years. Curcumin is a polyphenolic natural compound extract from the rhizomes of Curcuma longa Linn (Zingiberaceae family) which showed important anticancer effects by inhibiting cell proliferation and inducing apoptosis in several cancer types. Recently, some studies reported that the oral curcumin lowered PSA levels, but it did not modify the clinical outcomes in patients with prostate cancer who received intermittent androgen deprivation (IAD). Other studies reported that high concentrations of curcumin were toxic for patients.
Methods and results
In this study we showed that low doses of curcumin can induce senescence-like effects in 22rv1 cell line while higher concentrations have cytotoxic effects. Five,15 and 30 µM curcumin blocked cell cycle in G2/M phase but only 15 and 30 µM curcumin induced cell death. In addition, an increased expression of p21, a known senescence marker, was detected in 22Rv1cells treated with curcumin in every experimental condition.
Conclusion
In the context of personalized approach in PCa care, we suggest that the appropriate concentration of curcumin used in combination with radiotherapy or with androgen deprivation therapy (ADT) could take into consideration.
Ultra-Hypermutation Driven by POLE Mutation in Metastatic Colorectal Cancer: A Case for Immunotherapy Without dMMR
Authors: Li Xiaozhuang , Tang Chuanyun , Zhang Hongli , Zhou Zhiyong , Ma Junpeng , Yuan Xin , Zhong Ziwei , Chen Jing , Peng Huiyun , Zhang Chengsheng 
Published: December 2024

Abstract

Colorectal cancer (CRC) is among the leading causes of cancer-related mortality globally. Metastatic colorectal cancer (mCRC) with ultra-hypermutation is uncommon and its underlying pathogenesis remains incompletely characterized. Additionally, the response to immunotherapy in ultra-hypermutated mCRC is not well defined. Here we report a unique case of a 33-year-old Chinese woman with right-sided colon adenocarcinoma harboring somatic mutations in the POLE (p.A465V), MSH6 (p.G237*), and MSH2 (p.T934M) genes. Despite the presence of MSH6 and MSH2 mutations, immunohistochemistry (IHC) did not show mismatch repair deficiency (dMMR). Genomic analysis revealed high microsatellite instability (MSI-H) and an markedly elevated tumor mutational burden (TMB) of 275.25 Mut/Mb. The patient was initially treated with a combination of nivolumab, capecitabine, and oxaliplatin. Following a favorable response observed through CT and MRI scans after the first treatment cycle, the patient has commenced a second cycle of therapy. To our knowledge, this is the first reported case of ultra-hypermutated mCRC with rare mutations in POLE (p.A465V), MSH6 (p.G237*), and MSH2 (p.T934M) without dMMR, evaluating the efficacy of immune checkpoint inhibitors in this setting.
Physical Activity, Sedentary Behavior and Risk of Inflammatory Bowel Disease
Authors: Xia Siqin , Zhang Jie , Zhang Zixing , Wang Xiang , Ye Dongqing , Fang Xinyu 
Published: December 2024

Abstract

Background: Evidence linking physical activity (PA) and sedentary behavior (SB) to the development of inflammatory bowel disease (IBD) is inconsistent, and their joint associations with disease remain to be determined.
Objective: This study aimed to examine the separate and joint association of PA and SB with IBD risk.
Methods: The research contained 355,021 people with no IBD at baseline in the UK biobank. Information on PA (measured using the International Physical Activity Questionnaire) and SB (sum of computer using, television watching, and driving behavior) were collected. Using Cox proportional hazard models to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for IBD, Crohn’s disease (CD) and ulcerative colitis (UC) risks, while restricted cubic splines (RCS) assessing nonlinear relationships.
Results: During 13.6 years of follow-up, 2,242 incident IBD cases (664 CD and 1,481 UC) were recorded. Compared to the low level of PA, IBD risk was found to be lower for moderate and high PA, with HRs of 0.80 (95% CI: 0.72-0.89, p<0.001) and 0.87 (95% CI: 0.78-0.98, p=0.02), respectively. We also found a nonlinear correlation of PA with IBD risk (p<0.05 for nonlinearity), with a moderate level of PA (~2000 MET min/wk) offering the lowest risk. Besides, each additional hour of SB per day increased IBD risk (HR: 1.03; 95% CI: 1.01-1.05; p<0.001). The risk reduction from moderate and high levels of PA attenuated the adverse effects of long SB (≥6 hours/day), decreasing the risk by 18% and 27%, respectively. The results of PA and SB together on IBD risk showed that participants with low PA and long SB have the highest IBD risk.
Conclusions: The results revealed that promoting PA and reducing SB are beneficial for attenuating the risk of IBD. Individuals combining high PA with lowest SB time are at the lowest probability of developing IBD.
Clinical Utility of a Risk Scoring System for Individualized Treatment of Cesarean Scar Pregnancy
Authors: Sun Haiying , Wang Juan , Zhou Ting , Wang Shixuan , Liu Ronghua 
Published: December 2024

Abstract

Background Cesarean scar pregnancy (CSP) is a condition closely associated with previous cesarean section scars, and improper diagnosis or treatment may result in massive hemorrhage and life-threatening risks. Currently, there is a lack of standardized treatment guidelines or consensus for CSP, leading to a chaotic array of treatment methods. The objective of this study is to formulate a novel CSP scorecard model to aid in the selection of treatment plans for CSP.
Methods A cohort comprising 1,248 patients diagnosed with CSP was examined over a period from January 2013 to January 2023. Univariate and multivariate logistic regression analyses were employed to identify high-risk factors predictive of CSP risk, which served as the foundation for constructing a nomogram. The predictive efficacy of the nomogram was assessed through the application of receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA) curves.
ResultsSix risk factors—gestational age, gestational sac (GS) area, residual myometrial thickness, the relationship between the GS and scar, preoperative hemoglobin levels, and preoperative HCG—were evaluated as predictor variables in the nomogram. The nomogram demonstrated excellent discriminative ability, as evidenced by an area under the receiver operating characteristic (ROC) curve (AUC) of 0.84. Furthermore, the calibration curves and decision curve analysis indicated that the nomogram exhibited strong consistency and substantial clinical utility.
Conclusion This newly developed risk scoring system offers an effective tool for clinicians to tailor individualized CSP treatment plans.
A 7-year retrospective study：Comparison of the efficacy between rotational osteotomy at the base of femoral neck and vascularized iliac bone flap transfer in the treatment of osteonecrosis of the femoral head
Authors: Xia Tianwei , Sun Jiahao , Wang Lu , Zheng Shanbin , Liu Jinzhu , Chen Zhiyuan , Li Muzhe , Guo Yang , Shen Jirong , Ma Yong 
Published: December 2024

Abstract

Objective: To compare the clinical efficacy of rotational osteotomy at the base of femoral neck and iliac bone flap transfer with ascending branch of lateral femoral circumflex artery(vascularized iliac bone flap transfer) in the treatment of ARCO III stage, CJFH-L type osteonecrosis of femoral head.
Methods: We compared 25 cases (Group A), in which 25 hips underwent rotational osteotomy at the base of femoral neck and 25 cases (Group B) , in which 25 hips underwent vascularized iliac bone flap transfer in our hospital from September 2017 to March 2024.The operative time and hospitalization time were compared, the collapse and repair of femoral head and the healing of osteotomy were evaluated, and the reasons of failure were analyzed.
Results: All operations were conducted successfully in both groups. The follow-up time was 36.2 ± 21.62 months. The operation time in Group A was (215.20 ± 56.80) minutes, which was longer than that in Group B (190.21 ± 54.40) minutes (P <0.05) . There was no significant difference in the hospitalization time between the two groups. There was no significant difference in Harris scores between Group A and group B before operation (P<0.05). However, there was significant difference in Harris scores after 3 months, 6 months and at the last follow-up (P <0.05) . In Group A and Group B, there were significant differences 3 months after operation, 6 months after operation and at the last follow-up (P <0.05) . The excellent and good rate of Group A was 36% (9 hips) , the good rate of Group B was 44% (11 hips) . During the longest 7-year follow-up period, 6 hips in Group A and 4 hips in Group B underwent arthroplasty. In addition, one hip in group A underwent total hip exclusion because of infection. DCE-MRI showed that abnormal hyperperfusion of the repaired area was alleviated, and the blood supply of the necrotic area was restored.
Conclusion: Both rotational osteotomy of the base of the femoral neck under surgical dislocation and vascularized iliac bone flap transfer can obtain satisfactory short-term results in the treatment of CJFH-L type，ARCO III stage osteonecrosis of the femoral head. Rotational osteotomy at the base of femoral neck under surgical dislocation can be chosen to delay the collapse process for CJFH-L2 type、ARCOⅢB stage ONFH. Vascularized iliac bone flap transfer has the advantage of short operation time. It is easier and suitable for CJFH-L1 type、ARCOⅢA stage ONFH.
Efficacy and safety of nivolumab plus cabozantinib in octogenarian patients with advanced renal cell carcinoma
Authors: Nemoto Yuki , Endo Takanori , Segawa Hogara , Nakamura Kazutaka , Nishimura Koichi , Horiuchi Toshihide , Toki Daisuke , Kobayashi Hirohito , Takagi Toshio , Kondo Tsunenori 
Published: December 2024

Abstract

Purpose
To clarify the efficacy and safety profile of nivolumab plus cabozantinib combination therapy in advanced renal cell carcinoma patients older than 80 years.
Methods
We retrospectively evaluated 42 patients with advanced renal cell carcinoma treated with nivolumab plus cabozantinib as the first-line therapy at our institution. The patients were categorized according to age as those aged ≥ 80 years and those aged < 80 years. Efficacy was analysed by comparing the progression-free survival, overall survival, objective response rate, and disease control rate between the two groups. Safety was assessed by comparing the incidence of adverse events.
Results
Ten patients (31%) were classified as age ≥ 80 group. No significant differences were observed in the progression-free survival (p = 0.682), the overall survival (p = 0.627), objective response rate (p = 0.195), and disease control rate (p = 0.070) between the two groups. There was no significant difference in the incidence of all grades of adverse events(p = 1.000), but there was a trend toward a higher incidence of grade 3 or higher adverse events in the group of patients aged < 80 years (p = 0.066).
Conclusions
The efficacy and safety of nivolumab plus cabozantinib combination therapy were comparable between the patients aged ≥ 80 years and those aged < 80 years. Thus, chronological age alone is not a contraindication for nivolumab plus cabozantinib combination therapy for advanced renal cell carcinoma.
Sampling frequency matters: mapping of the healthy infants' gut microbiome during the first year of life
Authors: Micenková Lenka , Smetanová Soňa , Marciniak Jacek , Brodíková Kristýna , Kleknerová Dominika Polaštík , Lakotová Barbora , Zwinsová Barbora , Thon Vojtěch , Vídeňská Petra , Budinská Eva 
Published: December 2024

Abstract

Background
Previous studies described the impact of various early life events on the developing gut environment of infants. Nevertheless, a comprehensive understanding of the time frame of the response of the healthy microbiome to specific factors, such as vaccination, introduction of solid foods etc., and the duration of these changes is currently lacking. Hence, determining the optimal sampling frequency to effectively monitor the complex development of the gut microbiome remains a challenge.
Methods
To address these gaps, we monitored the plasticity of the gut microbiome using 16S rRNA gene sequencing almost on a daily basis in one infant (infant A) and weekly in twelve other infants (B-M) during their first year of life. We associated these changes with external factors and monitored their length.
Results
With respect to the first occurrence and dynamics of changes in the abundance of bacterial genera in all infants, three dominant groups of bacteria emerged, comprising "Early-life colonizers", "Re-appearing colonizers" and "Later-colonizers". Supporting the hypothesis that weekly sampling may not capture microbiota changes accurately, we found that a range of individual samples analyzed within a week varied by over 1 Shannon index, with coefficients of variation exceeding 10% in 19 weeks. While alpha diversity indicators showed decreased variability with age, beta diversity variability remained high at the end of the first year. In particular, the introduction of solid food and probiotics led to gradual but significant changes in bacterial composition, with the duration and extent of the changes varying between infants.
Conclusions
In our unique study, for the first time, we described in detail the mode of bacterial stages and colonizers in infants during the first year of life, finding that a similar colonization motif was observed regardless of sampling frequency. We showed that sparse weekly sampling hindered a comprehensive understanding of how key factors - such as the maternal microbiome, probiotics, diet, vaccinations, and unforeseen variables - affect the child's microbiome over time and in response to specific events early in life. Analysis of weekly variability in alpha and beta diversity suggests that such rare sampling may not be sufficient in terms of the outcomes of interest.
Prenatal Exome Sequencing of Fetuses with Central Nervous System Anomalies Based on Prenatal Ultrasound and Magnetic Resonance Imaging Diagnosis — A Retrospective Cohort Study and System Review
Authors: Yao Miss Jia , Wang Yan , Li Gang , Zhang Zhitao , Lv Yuan , Chen Lizhu 
Published: December 2024

Abstract

Background
Assessing the incremental yield of prenatal exome sequencing (ES) over chromosomal microarray analysis (CMA) in the diagnosis of central nervous system (CNS) anomalies based on prenatal ultrasound and magnetic resonance imaging (MRI) diagnoses.
Methods
In this retrospective cohort study, we collected the ES results of fetuses diagnosed with CNS anomalies through prenatal ultrasound and MRI between 2019 and 2023, who also had negative CMA results. We performed subgroup analyses to assess detection rates for different phenotypes in order to identify associated genes and variants. A meta-analysis combining our study with relevant research was performed to further explore the association between phenotype and ES.
Results
In the cohort study of 219 cases, ES identified pathogenic/likely pathogenic single nucleotide variations in 36 cases (16%). The highest detection rate was observed in cases with multisystem malformations (25%, 14/55), followed by multiple CNS anomalies (15%, 2/13) and isolated CNS anomaly (13%, 20/151). The most commonly identified isolated CNS anomaly was agenesis of the corpus callosum (31%, 5/16). Neural tube defects with urogenital anomalies were strongly linked to positive ES results (57%, 4/7). The meta-analysis of 989 cases from 22 studies showed a pooled ES diagnostic yield of 27% [(95% (CI), 21–34%)]. The highest detection rates were in cases of corpus callosum anomalies with facial abnormalities (75%, 8/11) and neural tube defects with urogenital malformations (80%, 12/15). The detection rate for three or more types of complex central nervous system (CNS) abnormalities was 43% (95% confidence interval, 31%-58%), which was significantly higher than that for only two abnormalities, which was 10% [(95% (CI), 4%-18%). No significant difference in diagnostic yield was found between cases identified by prenatal MRI combined with ultrasound [27% (95% confidence interval, 20–36%)] and those identified by ultrasound alone [25% (95% confidence interval, 17–35%)].
Conclusions
ES provided a significantly higher diagnostic yield than CMA for fetuses with CNS abnormalities. Additionally, diagnostic rates for variants varied across different phenotypic abnormalities.
Construction of high protein-producing mutant yeast strains via point and structural mutageneses and their use for carotenoid production
Authors: Yamada Ryosuke , Inoue Yoshifumi , Karitani Yukino , Sakaguchi Rumi , Matsumoto Takuya , Ogino Hiroyasu 
Published: December 2024

Abstract

Yeast Saccharomyces cerevisiae is a safe microorganism with established industrial-scale culture techniques, making it a useful host for protein and chemical production through metabolic engineering. Therefore, S. cerevisiae platform strains with high protein production are needed. In this study, we aimed to develop mutant S. cerevisiae strains with high protein production using techniques to introduce point and structural mutations. Point and structural mutations were introduced into the YPH499/pEUPGGFP strain, which expresses green fluorescent protein (GFP) in S. cerevisiae YPH499, and mutant strains were selected based on their fluorescence intensity. Consequently, YPH499/pEUPGGFP/Mu10G39, with a GFP fluorescence intensity 2.5-fold higher than that of the parent strain, was successfully obtained. Then, GFP expression plasmid was removed from the mutant and a carotenoid-producing plasmid was introduced to construct YPH499Mu10G39/pEU20Beta3. YPH499Mu10G39/pEU20Beta3 produced 6.74 mg/g-dry cell carotenoids after 72 h of culture, which was 2.9-fold higher than that produced by the parent strain. Transcriptome analysis suggested that YPH499Mu10G39 exhibited improved energy production, amino acid precursor supply, ribosome function, and stress tolerance, which may have contributed to its high protein production. In conclusion, by introducing point and structural mutations, we successfully developed the platform strain, YPH499Mu10G39, which is useful for the high production of various proteins. In the future, various proteins and useful chemicals can be produced through metabolic engineering using YPH499Mu10G39 as a platform strain.