bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between tamoxifen and incidence of osteoporosis in Korean patients with ductal carcinoma in situ
Authors: Kim Dooreh , Oh Jooyoung , Lee Hye Sun , Jeon Soyoung , Park Woo-Chan , Yoon Chang Ik 
Published: January 2024

IntroductionThe partial estrogen-agonist action of tamoxifen on bone receptors has beneficial effects on bone mineral density. However, in premenopausal women, the use of tamoxifen causes systemic estrogen depletion, which has detrimental effects on bone health. We aim to investigate the association between tamoxifen and osteoporosis in the real world using data from a longitudinal nationwide cohort of Korean patients.MethodsData were collected from the National Health Insurance claims database in South Korea. Osteoporosis was defined by diagnostic codes accompanying prescription data for osteoporosis. The cumulative incidence was analyzed by Kaplan–Meier survival curves and the risk factors were analyzed using a multivariable Cox proportional hazard regression model.ResultsBetween 2009 and 2015, of the 4,654 women with ductal carcinoma in situ (DCIS) without prior osteoporosis, 2,970 were prescribed tamoxifen and 1,684 were not. A total of 356 DCIS survivors were later diagnosed with osteoporosis during a median follow-up period of 84 months. In the overall population, tamoxifen was associated with a low risk of osteoporosis, before and after propensity matching adjusted for age, operation type, and comorbidities (before matching, hazard ratio [HR]=0.69, 95% confidence interval [CI]=0.559–0.851, p&lt;0.001; after matching, HR=0.664, 95% CI=0.513–0.858, p=0.002). In the subgroup analysis, findings were consistent in postmenopausal women but were not evident in the younger age group.ConclusionIn a nationwide cohort study, a low risk of osteoporosis was associated with the use of tamoxifen. The protective effect of tamoxifen was more profound in older women and was not related to the incidence of osteoporosis in younger women.
Axillary management in patients with clinical node-negative early breast cancer and positive sentinel lymph node: a systematic review and meta-analysis
Authors: Li Changzai , Zhang Pan , Lv Jie , Dong Wei , Hu Baoshan , Zhang Jinji , Zhu Hongcheng 
Published: January 2024

BackgroundThe omission of axillary lymph node dissection (ALND) or axillary radiation (AxRT) remains controversial in patients with clinical node-negative early breast cancer and a positive sentinel lymph node.MethodsWe conducted a comprehensive review by searching PubMed, Embase, Web of Science, and Cochrane databases (up to November 2023). Our primary outcomes were overall survival (OS), disease-free survival (DFS), locoregional recurrence (LRR), and axillary recurrence (AR).ResultsWe included 26 studies encompassing 145,548 women with clinical node-negative early breast cancer and positive sentinel lymph node. Pooled data revealed no significant differences between ALND and sentinel lymph node biopsy (SLNB) alone in terms of OS (hazard ratio [HR]0.99, 95% confidence interval [CI] 0.91-1.08, p=0.84), DFS (HR 1.04, 95% CI 0.90-1.19, p=0.61), LRR (HR 0.76, 95% CI 0.45-1.20, p=0.31), and AR (HR 1.01, 95% CI 0.99-1.03, p=0.35). Similarly, no significant differences were observed between AxRT and SLNB alone for OS (HR 0.57, 95% CI 0.32-1.02, p=0.06) and DFS (HR 0.52, 95% CI 0.26-1.05, p=0.07). When comparing AxRT and ALND, a trend towards higher OS was observed the AxRT group (HR 0.08, 95% CI 0.67-1.15), but the difference did not reach statistical significance (p=0.35, I2 = 0%). Additionally, no significant differences significance observed for DFS or AR (p=0.13 and p=0.73, respectively) between the AxRT and ALND groups.ConclusionOur findings suggest that survival and recurrence rates are not inferior in patients with clinical node-negative early breast cancer and a positive sentinel lymph node who receive SLNB alone compared to those undergoing ALND or AxRT.
Management and outcomes of brain metastases from pancreatic adenocarcinoma: a pooled analysis and literature review
Authors: Gouton Etienne , Gilabert Marine , Launay Simon , Loir Elika , Tyran Marguerite , Rochigneux Philippe , Turrini Olivier , Garnier Jonathan , Mitry Emmanuel , Chanez Brice 
Published: January 2024

BackgroundBrain metastases (BM) are rare in pancreatic ductal adenocarcinoma (PDAC) and little data exists concerning these patients and their outcomes.AimWe aimed to analyze the management, practices, and outcomes of patients presenting BM from PDAC both in our institution and in all cases reported in the literature.MethodsWe conducted a retrospective, monocentric analysis using a data mining tool (ConSoRe) to identify all patients diagnosed with PDAC and BM in our comprehensive cancer center (Paoli-Calmettes Institute), from July 1997 to June 2022 (cohort 1). Simultaneously, we reviewed and pooled the case reports and case series of patients with PDAC and BM in the literature (cohort 2). The clinical characteristics of patients in each cohort were described and survival analyses were performed using the Kaplan-Meier method.ResultsIn cohort 1, 19 patients (0.3%) with PDAC and BM were identified with a median age of 69 years (range: 39-81). Most patients had metastatic disease (74%), including 21% with BM, at diagnosis. Lung metastases were present in 58% of patients. 68% of patients had neurological symptoms and 68% were treated by focal treatment (surgery: 21%, radiotherapy: 42%, Gamma Knife radiosurgery: 5%). In cohort 2, among the 61 PDAC patients with BM described in the literature, 59% had metastatic disease, including 13% with BM at diagnosis. Lung metastases were present in 36% of patient and BM treatments included: surgery (36%), radiotherapy (36%), radiosurgery (3%), or no local treatment (25%). After the pancreatic cancer diagnosis, the median time to develop BM was 7.8 months (range: 0.0-73.9) in cohort 1 and 17.0 months (range: 0.0-64.0) in cohort 2. Median overall survival (OS) in patients of cohort 1 and cohort 2 was 2.9 months (95% CI [1.7,4.0]) and 12.5 months (95% CI [7.5,17.5]), respectively.ConclusionBM are very uncommon in PDAC and seem to occur more often in younger patients with lung metastases and more indolent disease. BM are associated with poor prognosis and neurosurgery offers the best outcomes and should be considered when feasible.
Acupuncture in musculoskeletal pain: analysis of changes in pain perception using the NRS (Numeric Rating Scale)
Authors: Fracchia Lorenzo , Olivero Alda Maria , Rustichelli Riccardo , Pedrali Tiziana 
Published: January 2024

ObjectivesThis study is based on data collected at the Acupuncture clinic of the Local Health Authority (ASL) in Turin from 2008 to 2022 and aims at evaluating the effectiveness of acupuncture in the treatment of musculoskeletal pain using the Numeric Rating Scale (NRS) which analyzes changes in pain perceived by patients in different body regions.MethodsThe database consists of data provided by patients during the initial visit and the last session. Only patients who provided data at the beginning and end of treatment were included. The data were processed using JASP 0.17.2.1 software. The sample consisted of 932 patients with musculoskeletal conditions, excluding 254 subjects with internal medical conditions, who were treated during the same period. The selected population includes individuals aged 23–94, comprising 242 men and 690 women. Patients followed a therapeutic protocol based on the initial diagnosis and underwent an initial cycle of six weekly sessions, with the possibility of four additional sessions if needed. Acupuncture was performed by experienced medical personnel following Traditional Chinese Medicine guideline.ResultsThe average NRS values were 7.49 at the beginning and 4.27 at the end, with a 43% reduction in pain. The data were analyzed using the Wilcoxon test, confirming statistical significance (p &lt; 0.001). They were then divided by body region, showing a reduction in pain ranging from 40% to 55%. Statistical analysis among different conditions was performed using the Kruskal–Wallis test, with further comparisons using the Dunn test.DiscussionThe study demonstrates that acupuncture is effective in reducing musculoskeletal suffering, with a significant decrease in pain perceived by patients. The results suggest that acupuncture can be a valid treatment for a wide range of conditions, with pain reduction ranging from 40% to 55% and greater effectiveness for elbow-related conditions. However, it is important to note that sample size may influence the results, and further research is needed to confirm and expand these findings, especially for less-represented conditions by the sample.
An analysis of Pompe newborn screening data: a new prevalence at birth, insight and discussion
Authors: Colburn Ryan , Lapidus David 
Published: January 2024

This study includes over 11.6M newborns screened (NBS) for Pompe Disease (PD) from 29 distinct universal screening programs across 8 countries and 4 continents. The birth prevalence of PD is 1:18,711, with no evidence of difference across populations of European, Latin American, or Asian ancestry, though differences may exist for PD subtypes. This study also compares these results, based on direct detection of disease and analyzed using a binomial method along with power analysis, with other methods for estimating the ‘frequency’ of rare genetic diseases (such as utilizing Hardy-Weinberg equilibrium on allele frequency and confidence interval analysis). This comparison demonstrates the implications of sample size and frames a discussion on its influence on the reliability of results when extrapolating to a population beyond the study dataset.ObjectivesPrimary: Establish a new figure for prevalence at birth for Pompe disease by collecting and analyzing the largest relevant dataset to date and using that result to project population prevalence at birth in a novel way. Secondary: Compare these results to previous analyses to offer a framework for evaluating ‘frequency’ data that can be applied to other rare, genetic diseases, along with methods to assess quality of estimates.
Neuroprotective effects and possible mechanisms of berberine in animal models of Alzheimer’s disease: a systematic review and meta-analysis
Authors: Dan Lijuan , Hao Yanwei , Li Jiaxin , Wang Tianyuan , Zhao Weiwei , Wang Hui , Qiao Liyan , Xie Peijun 
Published: January 2024

Background: Recently, multiple preclinical studies have reported the beneficial effect of berberine in the treatment of Alzheimer’s disease (AD). Nevertheless, the neuroprotective effects and possible mechanisms of berberine against AD are not universally recognized. This study aimed to conduct a systematic review and meta-analysis by integrating relevant animal studies to assess the neuroprotective effects and potential mechanisms of berberine on AD.Methods: We systematically searched PubMed, Embase, Scopus and Web of Science databases that reported the effects of berberine on AD models up to 1 February 2023. The escape latency, times of crossing platform, time spent in the target quadrant and pro-oligomerized amyloid beta 42 (Aβ1-42) were included as primary outcomes. The secondary outcomes were the Tau-ps 204, Tau-ps 404, β-site of APP cleaving enzyme (BACE1), amyloid precursor protein (APP), acetylcholine esterase (AChE), tumor necrosis factor ⍺ (TNF-α), interleukin 1β (IL-1β), IL-6, nitric oxide (NO), glial fibrillary acidic protein (GFAP), malonaldehyde (MDA), glutathione S-transferase (GST), glutathione (GSH), glutathione peroxidase (GPx), Beclin-1 and neuronal apoptosis cells. This meta-analysis was conducted using RevMan 5.4 and STATA 15.1. The SYRCLE’s risk of bias tool was used to assess the methodological quality.Results: Twenty-two studies and 453 animals were included in the analysis. The overall results showed that berberine significantly shortened the escape latency (p &lt; 0.00001), increased times of crossing platform (p &lt; 0.00001) and time spent in the target quadrant (p &lt; 0.00001), decreased Aβ1-42 deposition (p &lt; 0.00001), Tau-ps 202 (p &lt; 0.00001) and Tau-ps 404 (p = 0.002), and improved BACE1, APP, AChE, Beclin-1, neuronal apoptosis cells, oxidative stress and inflammation levels.Conclusion: Berberine may be a promising drug for the treatment of AD based on preclinical evidence (especially when the dose was 5–260 mg/kg). The potential mechanisms for these protective effects may be closely related to anti-neuroinflammation, anti-oxidative stress, modulation of autophagy, inhibition of neuronal apoptosis and protection of cholinergic system. However, these results may be limited by the quality of existing research. Larger and methodologically more rigorous preclinical research are needed to provide more convincing evidence.
Efficacies and ADME properties of redox active methylene blue and phenoxazine analogues for use in new antimalarial triple drug combinations with amino-artemisinins
Authors: Watson Daniel J. , Laing Lizahn , Petzer Jacobus P. , Wong Ho Ning , Parkinson Christopher J. , Wiesner Lubbe , Haynes Richard K. 
Published: January 2024

Efforts to develop new artemisinin triple combination therapies effective against artemisinin-tolerant strains of Plasmodium falciparum based on rational combinations comprising artemisone or other amino-artemisinins, a redox active drug and a third drug with a different mode of action have now been extended to evaluation of three potential redox partners. These are the diethyl analogue AD01 of methylene blue (MB), the benzo [α]phenoxazine PhX6, and the thiosemicarbazone DpNEt. IC50 values in vitro against CQ-sensitive and resistant P. falciparum strains ranged from 11.9 nM for AD01–41.8 nM for PhX6. PhX6 possessed the most favourable pharmacokinetic (PK) profile: intrinsic clearance rate CLint was 21.47 ± 1.76 mL/min/kg, bioavailability was 60% and half-life was 7.96 h. AD01 presented weaker, but manageable pharmacokinetic properties with a rapid CLint of 74.41 ± 6.68 mL/min/kg leading to a half-life of 2.51 ± 0.07 h and bioavailability of 15%. DpNEt exhibited a half-life of 1.12 h and bioavailability of 8%, data which discourage its further examination, despite a low CLint of 10.20 mL/min/kg and a high Cmax of 6.32 µM. Efficacies of AD01 and PhX6 were enhanced synergistically when each was paired with artemisone against asexual blood stages of P. falciparum NF54 in vitro. The favourable pharmacokinetics of PhX6 indicate this is the best partner among the compounds examined thus far for artemisone. Future work will focus on extending the drug combination studies to artemiside in vitro, and conducting efficacy studies in vivo for artemisone with each of PhX6 and the related benzo[α]phenoxazine SSJ-183.
Mechanism of Wuzhuyu decoction on alcohol-induced gastric ulcers using integrated network analysis and metabolomics
Authors: Wang Xin , Chen Lisheng , Chang Lei , He Yong , He Tingting , Wang Ruilin , Wei Shizhang , Jing Manyi , Zhou Xuelin , Li Haotian , Zhao Yanling 
Published: January 2024

Background: Gastric ulcers (GUs) are prevalent digestive disorders worldwide. Wuzhuyu Decoction (WZYT) is a traditional Chinese medicine that has been employed for centuries to alleviate digestive ailments like indigestion and vomiting. This study aims to explore the potential effects and underlying mechanisms of WZYT on alcohol induced gastric ulcer treatment.Methods: We employed macroscopic assessment to evaluate the gastric ulcer index (UI), while the enzyme-linked immunosorbent assay (ELISA) was utilized for detecting biochemical indicators. Pathological tissue analysis involved hematoxylin-eosin (H&amp;E) staining and Periodic Acid-Schiff (PAS) staining to assess gastric tissue damage. Additionally, the integration of network analysis and metabolomics facilitated the prediction of potential targets. Validation was conducted using Western blotting.Results: The research revealed that WZYT treatment significantly reduced the gastric ulcer index (UI) and regulation of alcohol-induced biochemical indicators levels. Additionally, improvements were observed in pathological tissue. Network analysis results indicated that 62 compounds contained in WZYT modulate alcohol-induced gastric ulcers by regulating 183 genes. The serum metabolomics indicated significant changes in the content of 19 metabolites after WZYT treatment. Two pivotal targets, heme oxygenase 1 (HMOX1) and albumin (ALB), are believed to assume a significant role in the treatment of gastric ulcers by the construction of “compounds-target-metabolite” networks. Western blot analysis confirmed that WZYT has the capacity to elevate the expression of HMOX1 and ALB targets.Conclusion: The integration of network analysis and metabolomics provides a scientific basis to propel the clinical use of WZYT for GUs. Our study provides a theoretical basis for the use of Wuzhuyu decoction in the treatment of gastric ulcers.
Vitamin D3 promotes gastric cancer cell autophagy by mediating p53/AMPK/mTOR signaling
Authors: Wang Yanan , He Qingmin , Rong Kang , Zhu Mingyang , Zhao Xiaoxiao , Zheng Pengyuan , Mi Yang 
Published: January 2024

Objective: Vitamin D3 has the general properties of a lipid-soluble vitamin, but is also an active steroid hormone that can regulate the proliferation, apoptosis and differentiation of many tumor cells, and exerts anticancer activity against numerous malignancies. However, the mechanism underlying the effects of vitamin D3 on tumors is not fully understood. Here, we used network pharmacology and in vitro experimental approaches to explore the mechanism of vitamin D3 activity in the context of gastric cancer.Methods: The Targetnet, SuperPred, SwissTargetPrediction, and PharmMapper databases were screened for potential drug-related targets, while we used data from the PharmGKB, Drugbank, OMIM, DisGeNET, CTD, and GeneCards databases to identify potential targets associated with gastric cancer. Disease-drug crossover genes were obtained by constructing Venn diagrams. Gene ontology and Kyoto Encyclopedia of Genomes (KEGG) enrichment analyses of crossover genes were conducted and STRING was used to generate protein interaction networks and identify core targets. CCK-8 experiments were performed and apoptosis detected to assess the effect of vitamin D3 on gastric cancer cells. Western blotting was applied to detect p53/AMPK/mTOR signaling, as well as autophagy-, cell cycle-, and apoptosis-related proteins.Results: A total of 485 targets of vitamin D3 activity were obtained and 1200 gastric cancer disease-related targets discovered. Further, 60 potential targets for vitamin D3 in gastric cancer treatment were identified. KEGG analysis indicated that potential targets were mainly involved in the cell cycle, HIF-1 signaling, and the AMPK pathway, among other pathways. These findings were validated using cellular experiments, which demonstrated that the viability of AGS and SGC-7901 cells was impeded by vitamin D3. Further, vitamin D3 promoted apoptosis and inhibited the cell cycle in those cell lines, as well as activating the p53/AMPK/mTOR pathway, which promotes autophagy and inhibits tumor development.Conclusion: Our network pharmacological analyses provide preliminarily data supporting a role for vitamin D3 in promoting autophagy and apoptosis in gastric cancer cells, and in activating the p53/AMPK/mTOR pathway, which inhibits gastric cancer cell proliferation. Our findings demonstrate the molecular mechanism underlying the effect of vitamin D3 in cure of gastric cancer.
Turkey hen sperm storage tubule transcriptome response to artificial insemination and the presence of semen
Authors: Brady Kristen , Krasnec Katina , Hanlon Charlene , Long Julie A. 
Published: January 2024

Introduction: Sperm storage within the uterovaginal junction (UVJ) of avian species occurs in specialized structures termed sperm storage tubules (SSTs) and allows for prolonged storage of semen, though the molecular mechanisms involved in semen preservation are not well understood. Little work has been done examining how function of the SSTs is impacted by insemination and by semen present in the SSTs.Methods: Transcriptome analysis was performed on isolated SSTs from turkey hens receiving no insemination (control), sham-insemination, or semen-insemination at three timepoints (D1, D30, and D90 post-insemination). Bioinformatic and functional annotation analyses were performed using CLC Genomics Workbench, Database for Annotation, Visualization, and Integrated Discovery (DAVID), and Ingenuity Pathway Analysis (IPA). Pairwise comparisons and k-medoids cluster analysis were utilized to decipher differential expression profiles in the treatment groups.Results: The SST transcriptome of the semen inseminated group exhibited the greatest differences within the group, with differences detectable for up to 90 days post insemination, while control and sham-inseminated groups were more similar. In the semen-inseminated samples, upregulation of pathways relating to classical and non-classical reproductive signaling, cytoskeletal remodeling, physiological parameters of the local UVJ environment, and cellular metabolism was observed. In the sham-inseminated samples, upregulation of immune pathways and non-reproductive endocrine hormones was observed.Discussion: This work provides insights into the molecular level changes of the SST in response to insemination as well as to the presence of semen. Results from this study may have direct implications on fertility rates as well as potential strategies for avian semen cryopreservation protocols.