bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sixteen prescribed Chinese herbal medicines provide time-dependent cardiorenal and survival benefits in patients with overall and advanced diabetic kidney disease: a real-world study in Taiwan
Authors: Chen Hsiao-Tien , Tung Chien-Hsueh , Yu Ben-Hui , Chen Yi-Chun 
Published: August 2024

BackgroundA causal connection between oxidative stress and inflammation in diabetes, along with its associated renal and cardiovascular complications, has been established. Sixteen prescribed potentially renoprotective Chinese herbal medicines for diabetic kidney disease (PRCHMDKD), which are scientific Chinese medicine (botanical drug) and categorized into five classes (clearing heat, nourishing yin, dampness dispelling, tonifying qi, and harmonizing formulas), exhibit shared antioxidative properties and target multiple oxidative stress pathways. However, the time-response, cumulative effects, and safety (hyperkalemia risk) of these sixteen PRCHMDKD on cardiorenal and survival outcomes in patients with overall and advanced DKD remain unresolved.MethodsThis retrospective cohort study analyzed national health insurance claims data in 2000–2017. Four statistical methods, including Cox proportional hazards models, complementary restricted mean survival time (RMST), propensity score matching, and competing risk analysis for end-stage renal disease (ESRD), were employed to investigate this relationship. The study included 43,480 PRCHMDKD users and an equal number of matched nonusers within the overall DKD patient population. For advanced DKD patients, the cohort comprised 1,422 PRCHMDKD users and an equivalent number of matched nonusers.ResultsPRCHMDKD use in overall and advanced, respectively, DKD patients was associated with time-dependent reductions in adjusted hazard ratios for ESRD (0.66; 95% CI, 0.61–0.70 vs. 0.81; 0.65–0.99), all-cause mortality (0.48; 0.47–0.49 vs. 0.59; 0.50–0.70), and cardiovascular mortality (0.50; 0.48–0.53 vs. 0.61; 0.45–0.82). Significant differences in RMST were observed in overall and advanced, respectively, DKD patients, favoring PRCHMDKD use: 0.31 years (95% CI, 0.24–0.38) vs. 0.61 years (0.13–1.10) for ESRD, 2.71 years (2.60–2.82) vs. 1.50 years (1.03–1.98) for all-cause mortality, and 1.18 years (1.09–1.28) vs. 0.59 years (0.22–0.95) for cardiovascular mortality. Additionally, hyperkalemia risk did not increase. These findings remained consistent despite multiple sensitivity analyses. Notably, the cumulative effects of utilizing at least four or five classes and multiple botanical drugs from the sixteen PRCHMDKD provided enhanced renoprotection for patients with both overall and advanced DKD. This suggests that there is involvement of multiple targets within the oxidative stress pathways associated with DKD.ConclusionThis real-world study suggests that using these sixteen PRCHMDKD provides time-dependent cardiorenal and survival benefits while ensuring safety for DKD patients.
Comparative analysis of adverse event risks in breast cancer patients receiving pembrolizumab combined with paclitaxel versus paclitaxel monotherapy: insights from the FAERS database
Authors: Li Yilun , Yang Xiaolu , Ma Li 
Published: August 2024

ObjectiveThis study aimed to evaluate the risk of adverse events (AEs) in breast cancer patients treated with pembrolizumab combined with paclitaxel versus those receiving pembrolizumab or paclitaxel monotherapy, using the FDA Adverse Event Reporting System (FAERS) database.MethodsData were extracted from the FAERS database for breast cancer patients treated with pembrolizumab combined with paclitaxel or with pembrolizumab or paclitaxel monotherapy from Q1 2016 to Q2 2023. Disproportionation analysis was performed by calculating the reporting odds ratio (ROR) with corresponding 95% confidence interval (95% CI), the information component (IC), and the lower bound of the information component 95% confidence interval (IC025) to identify potential safety signals.ResultsNo significant difference in AEs was observed between the combined treatment group and the pembrolizumab monotherapy group. However, the combined treatment group exhibited a substantial increase in AE risk compared to the paclitaxel monotherapy group. The most significant increases in AE risk were adrenal insufficiency (ROR = 189.94, 95% CI 25.41–1419.7, IC = 3.37, IC025 = 1.59), hypophysitis (ROR = 99.46, 95% CI 12.72–777.4, IC = 3.31, IC025 = 1.44), and myocarditis (ROR = 69.5, 95% CI 8.55–565.23, IC = 3.25, IC025 = 1.33). The time-to-event for combined treatment was 35 (34–70) days, for pembrolizumab was 43 (35–90) days, and for paclitaxel was 42 (37–76) days. The combination therapy group demonstrated significantly shorter intervals to the onset of adrenal insufficiency (p = 0.008), myocarditis (p &lt; 0.001), and immune-related enterocolitis (p = 0.009).ConclusionAnalysis of the FAERS database indicates that combination therapy significantly elevates the risk of adrenal insufficiency, myocarditis, hypophysitis, and immune-related enterocolitis compared to paclitaxel monotherapy. These findings provide critical insights for clinicians in predicting and managing potential AEs associated with this treatment regimen.
E-learning pills on immunotherapy in urothelial carcinoma: The E-PIMUC program for continuing medical education
Authors: Romero-Clarà Olga , Madrid Clara , Pardo Juan Carlos , Ruiz de Porras Vicenç , Etxaniz Olatz , Moreno-Alonso Deborah , Font Albert 
Published: August 2024

BackgroundThe high incidence and mortality rates of urothelial carcinoma mean it remains a significant global health concern. Its prevalence is notably pronounced in industrialized countries, with Spain registering one of the highest incidences in Europe. Treatment options are available for various stages of bladder cancer. Moreover, the management landscape for this disease has been significantly transformed by the rapid advances in immunotherapy. Healthcare professionals who diagnose, treat, and follow up with bladder cancer patients need comprehensive training to incorporate these advances into their clinical practice. To bridge these knowledge gaps, we set up the E-PIMUC program to educate healthcare professionals on bladder cancer management and specifically immunotherapy.MethodsE-PIMUC used an innovative microlearning methodology comprising bitesize learning pills that support efficient acquisition of specialized expertise. We used a mixed methods, quantitative and qualitative approach to assess the success of the E-PIMUC program. Data collection encompassed pre-post testing, participation metrics, satisfaction surveys, and self-perceived performance assessments.ResultsA total of 751 healthcare professionals enrolled in the program. Of these, 81.0% actively engaged with the content and 33.2% passed all tests and were awarded the course certificate and professional credits. The course received satisfaction ratings of 94.3% to 95.1% and significantly improved the declarative knowledge of participants who had a range of professional profiles (p &lt; 0.001). Participants reported increased confidence in applying immunotherapy principles in their practice (average improvement of 1.4 points). Open-ended responses also underscored participants’ perceived benefits, including expanded knowledge and enhanced patient interaction skills.ConclusionThe E-PIMUC program provided effective, comprehensive, cutting-edge training on bladder cancer management, particularly on the use of immunotherapy in this area of oncology. The high participation rates, positive satisfaction scores, substantial knowledge enhancement, and improved self-perceived performance, are all testament to the program’s success. E-PIMUC was endorsed by regulatory bodies as a trusted educational resource in urothelial carcinoma management. What is more, complementary initiatives brought together patients and medical experts to foster a holistic, patient-centered approach to the complexities of bladder cancer care.
Tenofovir versus entecavir on the prognosis of hepatitis B virus-related hepatocellular carcinoma: a reconstructed individual patient data meta-analysis
Authors: Peng Jian-Xin , Wang Ling-Zhi , Wang Qiu-Ting , Li Hui-Long , Lin Li-Jun , He Jun-Ming 
Published: August 2024

Background: Hepatitis B, often leading to Hepatocellular carcinoma (HCC), poses a major global health challenge. While Tenofovir (TDF) and Entecavir (ETV) are potent treatments, their comparative effectiveness in improving recurrence-free survival (RFS) and overall survival (OS) rates in HBV-related HCC is not well-established.Methods: We conducted an individual patient data meta-analysis using survival data from randomized trials and high-quality propensity score-matched studies to compare the impact of Tenofovir (TDF) and Entecavir (ETV) on RFS and OS in HBV-related HCC patients. Data from six databases and gray literature up to 30 August 2023, were analyzed, utilizing Kaplan-Meier curves, stratified Cox models, and shared frailty models for survival rate assessment and to address between-study heterogeneity. The study employed restricted mean survival time analysis to evaluate differences in RFS and OS between TDF-treated and ETV-treated patients. Additionally, landmark analyses compared early (&lt;2 years) and late (≥2 years) tumor recurrence in these cohorts.Results: This study incorporated seven research articles, covering 4,602 patients with HBV-related HCC (2,082 on TDF and 2,520 on ETV). Within the overall cohort, TDF recipients demonstrated significantly higher RFS (p = 0.042) and OS (p &lt; 0.001) than those on ETV. The stratified Cox model revealed significantly improved OS for the TDF group compared to the ETV group (hazard ratio, 0.756; 95% confidence interval, 0.639–0.896; p = 0.001), a result corroborated by the shared frailty model. Over a follow-up period of 1–8 years, no significant difference was noted in the mean time to death between the TDF and ETV groups. The rates of early recurrence did not significantly differ between the groups (p = 0.735). However, TDF treatment was significantly associated with a reduced risk of late recurrence compared to ETV (p &lt; 0.001). In the HCC resection subgroup, the disparities in OS, early, and late recurrence rates between the two treatments paralleled those seen in the overall cohort.Conclusion: Compared to ETV, TDF may enhance OS and reduce late tumor recurrence risk in HBV-related HCC patients receiving curative treatment. However, there was no statistically significant distinction in the timing of tumor recurrence and mortality between patients administered TDF and those prescribed ETV.Systematic Review Registration:http://www.crd.york.ac.uk/prospero/.
Therapeutic potential of arginine deprivation therapy for gliomas: a systematic review of the existing literature
Authors: Yuxiao Chen , Jiachen Wang , Yanjie Lan , Shenglan Li , Yuji Wang , Wenbin Li 
Published: August 2024

BackgroundArginine deprivation therapy (ADT) hinders glioma cells’ access to nutrients by reducing peripheral blood arginine, showing great efficacy in various studies, which suggests it as a potentially promising treatment for glioma. The aim of this systematic review was to explore the mechanism of ADT for gliomas, the therapeutic effect based on existing research, and possible combination therapies.MethodsWe performed a systematic literature review of PubMed, ScienceDirect and Web of Science databases according to PRISMA guidelines, searching for articles on the efficacy of ADT in glioma.ResultsWe identified 17 studies among 786 search results, among which ADT therapy mainly based on Arginine free condition, Arginine Deiminase and Arginase, including three completed clinical trials. ADT therapy has shown promising results in vivo and in vitro, with its safety confirmed in clinical trials. In the early phase of treatment, glioblastoma (GBM) cells develop protective mechanisms of stress and autophagy, which eventually evolve into caspase dependent apoptosis or senescence, respectively. The immunosuppressive microenvironment is also altered by arginine depletion, such as the transformation of microglia into a pro-inflammatory phenotype and the activation of T-cells. Thus, ADT therapy demonstrates glioma-killing effect in the presence of a combination of mechanisms. In combination with various conventional therapies and investigational drugs such as radiotherapy, temozolomide (TMZ), cyclin-dependent kinase inhibitors (CDK) inhibitors and autophagy inducers, ADT therapy has been shown to be more effective. However, the phenomenon of drug resistance due to re-expression of ASS1 rather than stem cell remains to be investigated.ConclusionDespite the paucity of studies in the literature, the available data demonstrate the therapeutic potential of arginine deprivation therapy for glioma and encourage further research, especially the exploration of its combination therapies and the extrapolation of what we know about the effects and mechanisms of ADT from other tumors to glioma.
Combination of transcriptomic and proteomic approaches helps unravel the mechanisms of luteolin in inducing liver cancer cell death via targeting AKT1 and SRC
Authors: Ma Junxia , Mo Jinggang , Feng Yifu , Wang Liezhi , Jiang Hao , Li Junmin , Jin Chong 
Published: August 2024

IntroductionLuteolin, a natural compound commonly used in traditional Chinese medicine, shows clinical potential as an anti–liver cancer agent. The mechanisms underlying the anti–liver cancer effect of luteolin are limited versus those reported for other cancers. Accordingly, this study was conducted to bridge the existing knowledge gap.MethodsTranscriptomic and proteomic analyses of the response of the hepatocellular carcinoma cell line HuH-7 to luteolin were conducted, and a possible pathway was elucidated using confocal laser scanning microscopy (CLSM), flow cytometry, western blotting, qRT-PCR and bio-layer interferometry assay to systematically explore the possible mechanisms underlying the inhibition of the proliferation of liver cancer cells by luteolin.Results and DiscussionResults showed that luteolin significantly inhibited HuH-7 cell proliferation. Transcriptomic and proteomic analyses collectively revealed that luteolin could promote cell cycle arrest and apoptosis in HuH-7 cells through transcription factors p53, nuclear factor kappa B (NF-κB), FOXO, ATF2, and TCF/LEF via AKT1, as well as the KEAP-NRF and SRC-STAT3 pathways. Furthermore, AKT1 and SRC were identified as the 2 targets of luteolin. Nuclear translocation of transcription factors p53 and NF-κB were affected by luteolin administration. Additionally, AKT1 activity affected normal metabolism in HuH-7 cells and resulted in the accumulation of reactive oxygen species, which activated MOMP and further promoted apoptosis. Our results systematically elucidate the mechanism of luteolin in inhibiting the proliferation of liver cancer cells, mainly through cell cycle arrest and apoptosis via targeting AKT1 and SRC.
In elderly individuals, the effectiveness of sensorimotor training on postural control and muscular strength is comparable to resistance-endurance training
Authors: Varjan Mikuláš , Žiška Böhmerová Ľubica , Oreská Ľudmila , Schickhofer Peter , Hamar Dušan 
Published: August 2024

While classical resistance exercise is an effective way to improve strength and control postural sway, it may not be suitable for some elderly individuals with specific health disorders (e.g., aneurysms). Therefore, there is a need to explore alternative modalities. The study aimed to evaluate the effects of sensorimotor training on muscle strength and postural control in the female elderly population and subsequently compare these effects with a traditional combined resistance-endurance training program. A total of 34 healthy, active elderly women aged from 65 to 75 years, (average age 72.7 ± 4.4 years, height 161.6 ± 5.1 cm, and weight 66.9 ± 8.4 kg) were randomly assigned to three groups undergoing different 10-week interventions: the resistance-endurance training (RET, n = 11), the sensorimotor training (SMT, n = 12) and the control group (COG, n = 11). Prior to and after the interventions all participants underwent tests of maximal voluntary contraction of the dominant and non-dominant leg; postural sway tests with open and closed eyes; novel visual feedback balance test; 10-meter maximal walking speed (10 mMWS) and stair climb test. A T-test and repeated measures ANOVA were used, followed by the Bonferroni post hoc test, to compare the pre and post-measurements and assess differences in gains between groups. Results showed a significant main effect of time on strength (p &lt; 0.001). In addition, significant differences in time × group interaction on strength (p &lt; 0.01), postural control (p &lt; 01), and ascendant and descended vertical speed (p &lt; 0.001) were observed. Besides, the RET group improved significantly the maximal voluntary contraction of both dominant (16.3%, p ≤ 0.01) and non-dominant leg (10.9%, p ≤ 0.05). SMT group improved maximal voluntary contraction of both dominant (16.6%, p ≤ 0.001) and non-dominant leg (12.7%, p ≤ 0.01). In addition, they also improved mean velocity of the centre of pressure (COP) in postural sway test with eyes open (24.2%, p ≤ 0.05) as well as eyes closed (29.2%, p ≤ 0.05), mean distance of COP in novel visual feedback balance test (37.5%, p ≤ 0.001), ascendant and descended vertical velocity (13.6%, p ≤ 0.001 and 17.8%, p ≤ 0.001, respectively). Results show not only resistance training but sensorimotor intervention boosts strength too. This intervention also enhances postural control and functional abilities for both ascending and descending movements.
Human umbilical cord-derived mesenchymal stem cells alleviate valproate-induced immune stress and social deficiency in rats
Authors: Sun Shixiong , Luo Shilin , Chen Jie , Zhang Ou , Wu Qiongying , Zeng Nianju , Bi Jinlian , Zheng Chunbing , Yan Tenglong , Li Zhiyuan , Chen Jindong , Zhang Yilei , Lang Bing 
Published: August 2024

IntroductionAutism spectrum disorders (ASD) are a set of heterogeneous neurodevelopmental disorders characterized by impaired social interactions and stereotypic behaviors. Current clinical care is palliative at the most and there remains huge unmet medical need to fully address the core symptoms of ASD. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are emerging as a promising candidate for ASD treatment, but the precise mechanism remains controversial.MethodsIn vitro studies we performed the transwell migration assay to explore the interaction between hUC-MSCs and the primary-cultured cortical neurons. Then we determined the therapeutic effects of intravenous administration of hUC-MSCs in rats challenged with valproic acid (VPA) during gestation, a well-defined rat model of autism.ResultsOur studies showed that hUC-MSCs promoted the growth of primary-cultured cortical neurons. Furthermore, our results demonstrated that hUC-MSCs significantly alleviated microglial activation in the brain, especially in the anterior cingulate cortex, and effectively improved the sociability of the VPA-exposed rats.DiscussionThese results offer valuable insights for clinical translation and further research on the mechanisms of hUC-MSCs in psychiatric disorders characterized by microglial activation, particularly in cases of autism, shall be warranted.
Comparison among anorexia nervosa adolescents with or without previous overweight, obese, and healthy adolescents
Authors: Amianto Federico , Sertori Francesca , Davico Chiara , Marcotulli Daniele , Vitiello Benedetto 
Published: August 2024

BackgroundAnorexia nervosa (AN) and obesity (OB) are relevant concerns in adolescence. Despite their contrasting phenotypes, they share common pathogenic origins and may be present in the same individual at different times. We explored the psychopathology and attachment features of adolescents with AN who did (AN-ow) or did not (AN-nw) have previous overweight, compared with OB adolescents and healthy control (HC) adolescents.MethodIn total, 148 female adolescents referred to an outpatient clinic for an eating disorder (66 for AN and 42 for OB) and 40 HCs were assessed using self-administered instruments that measured parenting, attachment, eating, and general psychopathology. Group differences were tested by analysis of covariance, and correlations between variables were examined.ResultsAN-ow, AN-nw, and OB adolescents had greater interpersonal distrust and avoidance of relationships, compared with HC adolescents. AN-nw and AN-ow adolescents displayed a higher need for approval and a drive to thinness and interpersonal distrust, compared with HC adolescents. AN-ow adolescents displayed lower paternal care and higher ineffectiveness, asceticism, social insecurity, and depression, compared with HC adolescents. Compared with AN-nw adolescents, AN-ow adolescents felt more ineffective and more ascetic. The dynamics linking the psychopathological features clearly distinguished the four groups.ConclusionsAN-ow is a well-identified subtype of AN, with specific features that differ from AN-nw; some of these features are shared with OB. A therapeutic approach tailored to AN-ow adolescents should consider these features.
Translating research evidence into youth behavioral health policy and action: using a community-engaged storyboard approach
Authors: Parnes McKenna F. , Mehari Merih , Sedlar Georganna R. , Trevino Cindy , Porter Rachel , Walker Sarah C. 
Published: August 2024

IntroductionThere is nationwide shortage of child and adolescent behavioral health providers. Lack of diversity in the mental health care profession compounds workforce capacity issues, contributing to greater disparities in treatment access and engagement for youth from historically disenfranchised communities. Strategies are needed to foster cross-sector alignment to inform policy which can improve mental health care access and reduce disparities. This current case study details a specific research-practice-policy partnership strategy, storyboarding, as a method to engage community partners in Washington State to deliberate on information drawn from research on non-specialist models of child and adolescent mental health care to support the behavioral workforce expansion.MethodResearch evidence from a scoping literature review on non-specialist models of child and adolescent mental health care was shared via storyboards with community partners to inform policy efforts around the behavioral health workforce expansion. In Phase 1, community members with lived experience and clinical expertise contributed to the storyboard design process. In Phase 2, a broader community partner group shared their perspectives on the models of care presented in the storyboards via Qualtrics survey with open-ended questions. Listening sessions were also held with non-English speaking refugee and immigrant communities to elicit feedback on whether these models of care would meet their needs. Qualitative data was coded to explore emerging themes using a rapid deductive approach.ResultsCommunity partners shared mixed responses to models of care presented from the research literature. Immigrant and refugee communities explicitly stated these existing models would not fit their context. Regarding partnership strategy success, the smaller community partner group was engaged in the storyboard design process. The broader community interacted with and provided detailed responses to the models of care presented in the storyboards. Success was also reflected in community partners’ continued participation in the next stage of the project.DiscussionFindings demonstrate how storyboarding can be effectively used to translate research evidence into accessible information to promote community partner engagement and capture community voice in policy processes. More work is needed exploring how such methods can be used to increase the use of research evidence in policy and practice spaces.