bluuebunny/crossref_metadata_2025_split huggingface dataset:
A data-driven machine learning algorithm to predict the effectiveness of inulin intervention against type II diabetes
Authors: Yang Shuheng , Weiskirchen Ralf , Zheng Wenjing , Hu Xiangxu , Zou Aibiao , Liu Zhiguo , Wang Hualin 
Published: January 2025

IntroductionThe incidence of type 2 diabetes mellitus (T2DM) has increased in recent years. Alongside traditional pharmacological treatments, nutritional therapy has emerged as a crucial aspect of T2DM management. Inulin, a fructan-type soluble fiber that promotes the growth of probiotic species like Bifidobacterium and Lactobacillus, is commonly used in nutritional interventions for T2DM. However, it remains unclear which type of T2DM patients are suitable for inulin intervention. The aim of this study was to predict the effectiveness of inulin treatment for T2DM using a machine learning model.MethodsOriginal data were obtained from a previous study. After screening T2DM patients, feature election was conducted using LASSO regression, and a machine learning model was developed using XGBoost. The model’s performance was evaluated based on accuracy, specificity, positive predictive value, negative predictive value and further analyzed using receiver operating curves, calibration curves, and decision curves.ResultsOut of the 758 T2DM patients included, 477 had their glycated hemoglobin (HbA1c) levels reduced to less than 6.5% after inulin intervention, resulting in an incidence rate of 62.93%. LASSO regression identified six key factors in patients prior to inulin treatment. The SHAP values for interpretation ranked the characteristic variables in descending order of importance: HbA1c, difference between fasting and 2 h-postprandial glucose levels, fasting blood glucose, high-density lipoprotein, age, and body mass index. The XGBoost prediction model demonstrated a training set accuracy of 0.819, specificity of 0.913, positive predictive value of 0.818, and negative predictive value of 0.820. The testing set showed an accuracy of 0.709, specificity of 0.909, positive predictive value of 0.705, and negative predictive value of 0.710.ConclusionThe XGBoost-SHAP framework for predicting the impact of inulin intervention in T2DM treatment proves to be effective. It allows for the comparison of prediction effect based on different features of an individual, assessment of prediction abilities for different individuals given their features, and establishes a connection between machine learning and nutritional intervention in T2DM treatment. This offers valuable insights for researchers in this field.
An intraoperative nomogram for predicting secondary margin positivity in breast conserving surgery utilizing frozen section analysis
Authors: Li Cheng , Jiang Yan , Wu Xumiao , Luo Yong , Li Qi 
Published: January 2025

BackgroundBreast conserving surgery (BCS) is a standard treatment for breast cancer. Intraoperative frozen section analysis (FSA) is widely used for margin assessment in BCS. In addition, FSA-assisted excisional biopsy is still commonly practiced in many developing countries. The aim of this study is to develop a predictive model applicable to BCS with FSA-assisted excisional biopsy and margin assessment, with a focus on predicting the risk of secondary margin positivity in re-excision procedures following positive initial margins. This may reduce surgical complications and healthcare costs associated with multiple re-excisions and FSAs for recurrent positive margins.MethodsPatients were selected, divided into training and testing sets, and their data were collected. The Least Absolute Shrinkage and Selection Operator (LASSO) was used to identify significant variables from the training set for model building. Model performance was evaluated using Receiver Operating Characteristic (ROC) curves, calibration curves, and Decision Curve Analyses (DCAs). An optimal threshold identified by the Youden index was validated using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).ResultsThe study included 348 patients (256 in the training set, 92 in the testing set). No significant statistical differences were found between the sets. LASSO identified six variables to construct the model and corresponding nomogram. The model showed good discrimination (mean area under the curve (AUC) values of 0.79 in the training set and 0.83 in the testing set), calibration (Hosmer-Lemeshow test results (p-values 0.214 in the training set, 0.167 in testing set)) and clinical utility. The optimal threshold was set at 97 points in the nomogram, yielding a sensitivity of 0.66 (0.54-0.77), specificity of 0.80 (0.74-0.85), PPV of 0.56 (0.47-0.64) and NPV of 0.86 (0.82-0. 90) for the training set, and a sensitivity of 0.65 (0.46-0.84), specificity of 0.88 (0.79-0.95), PPV of 0.68 (0.53-0.85) and NPV of 0.87 (0.81-0.93) for the testing set, demonstrating the model’s effectiveness in both sets.ConclusionsThis study successfully developed a novel predictive model for secondary margin positivity applicable to BCS with FSA-assisted excisional biopsy and margin assessment. It demonstrates good discriminative ability, calibration, and clinical utility.
Investigating resistance to 5-Azacytidine and Venetoclax in PDX models of MDS/AML
Authors: Bašová Petra , Minařík Lubomír , Magalhaes-Novais Silvia Carina , Balounová Jana , Zemanová Zuzana , Aghová Tatiana , Špaček Martin , Jonášová Anna , Pimková Kristýna Gloc , Procházka Jan , Sedláček Radislav , Stopka Tomáš 
Published: January 2025

IntroductionProgressing myelodysplastic syndrome (MDS) into acute myeloid leukemia (AML) is an indication for hypomethylating therapy (HMA, 5-Azacytidine (AZA)) and a BCL2 inhibitor (Venetoclax, VEN) for intensive chemotherapy ineligible patients. Mouse models that engraft primary AML samples may further advance VEN + AZA resistance research.MethodsWe generated a set of transplantable murine PDX models from MDS/AML patients who developed resistance to VEN + AZA and compared the differences in hematopoiesis of the PDX models with primary bone marrow samples at the genetic level. PDX were created in NSGS mice via intraosseal injection of luciferase-encoding Lentivirus-infected MDS/AML primary cells from patient bone marrow. We validated the resistance of PDX-leukemia to VEN and AZA and further tested candidate agents that inhibit the growth of VEN/AZA-resistant AML.Results and discussionTransplantable PDX models for MDS/AML arise with 31 % frequency. The lower frequency of transplantable PDX models is not related to peritransplant lethality of the graft, but rather to the loss of the ability of short-term proliferation of leukemic progenitors after 10 weeks of engraftment. There exist subtle genetic and cytological changes between primary and PDX-AML samples however, the PDX models retain therapy resistance observed in patients. Based on in vitro testing and in vivo validation in PDX models, Panobinostat and Dinaciclib are very promising candidate agents that overcome dual VEN + AZA resistance.
Incorporating genotype information in a precise prediction model for platinum sensitivity in epithelial ovarian cancer
Authors: Du Nai-Yi , Li Yan , Zheng Hui , Liu Ya-Kun , Liu Lu-Sha , Xie Jianbang , Kang Shan 
Published: January 2025

ObjectiveDevelop a predicting model that can help stratify patients with epithelial ovarian cancer (EOC) before platinum-based chemotherapy.Methods148 patients with pathologically confirmed EOC and with a minimum 5-year follow-up were retrospectively enrolled. Patients were classified into platinum-sensitive and platinum-resistant groups according to treatment responses. The correlation between clinical factors and drug sensitivity was evaluated using statistical tests. Approximately 700,000 single-nucleotide polymorphism (SNP) sites were assessed for association with drug sensitivity via the Genome-wide Association Study (GWAS). LASSO regression and manual selection were employed to reduce the number of variables. A predicting model based on optimized variables was constructed. The predictive ability of the model was assessed using the Kaplan-Meier curve.ResultsNo statistically significant association was found between clinical factors and drug sensitivity. Sixteen SNPs were preserved after the optimization. A predicting model for drug sensitivity was constructed based on those sixteen SNPs. Coefficients of the synergistic effect for each SNP were determined, and an algorithm of the Drug Sensitivity Index (DSI) was built. The DSI score can successfully distinguish the drug-sensitive or drug-resistant patients with sensitivity, specificity, positive predictive value, and accuracy of 94.7%, 83.3%, 90.8%, and 90.5%, respectively. In both the training set and validating samples, the Kaplan-Meier curve showed that the median PFS and mean OS were significantly differentiated between the predicted sensitive and resistant patients (p-value&lt;0.001).ConclusionsA mathematical model incorporating genotype information could help predict the drug sensitivity of platinum-based chemotherapy before the treatment in EOC patients. A personal chemotherapy could be achieved based on the model.
Prognostic value of the pretreatment Naples prognostic score in patients with colorectal cancer: a systematic review and meta-analysis
Authors: Liu Hui , Zhu Dailiang , Jiang Dequan , Pang Huayang , Yang Xiaolian 
Published: January 2025

BackgroundThe prognostic significance of the Naples prognostic score (NPS) in colorectal cancer remains uncertain. This study aims to investigate the correlation between the pretreatment NPS and long-term oncological outcomes in patients with colorectal cancer.MethodsA comprehensive literature search of electronic databases, including PubMed, Embase, and Web of Science, was conducted up to July 1st, 2024. The primary outcomes assessed were survival outcomes. Subgroup analysis and sensitivity analysis were performed during the pooled analysis.ResultsEight studies including 2571 patients were included. The pooled results indicated that patients in the high NPS group exhibited significantly worse overall survival (HR= 2.08 95%CI: 1.74-2.48; P&lt;0.01; I2 = 0%) and disease-free survival (HR=2.03; 95%CI: 1.49-2.77; P&lt;0.01; I2 = 30%). Notably, the prognostic significance of NPS on both overall survival and disease-free survival was consistent across different geographical regions, tumor stages, and primary treatments examined in this study. Furthermore, sensitivity analyses confirmed the robustness of these combined results.ConclusionThe pretreatment NPS could serve as a valuable biomarker for predicting long-term oncological outcomes in patients diagnosed with colorectal cancer.
Development of novel nomograms for predicting prostate cancer in biopsy-naive patients with PSA < 10 ng/ml and PI-RADS ≤ 3 lesions
Authors: Chai Jia-gui , Li Yu-hang , Ke Chang-xing 
Published: January 2025

PurposeTo develop novel nomograms for predicting prostate cancer (PCa) and clinically significant prostate cancer (csPCa) in patients with prostate-specific antigen (PSA) &lt; 10 ng/ml and PI-RADS v2.1 score ≤ 3.MethodsWe retrospectively collected data from 327 men with PSA &lt; 10 ng/ml and PI-RADS score ≤ 3 from June 2020 to June 2024 in our hospital. Clinical data were compared among the PI-RADS scores 1-3 population, PI-RADS scores 1-2 population, and PI-RADS score 3 population. Logistic regression analyses were conducted to identify independent risk factors for PCa or csPCa, and nomograms were subsequently developed. The nomograms were evaluated via receiver operating curves (ROC), calibration curves, and decision curve analysis (DCA). Internal validation was conducted using bootstrap methods.ResultsAmong the 327 patients, 224 (68.50%) were diagnosed with benign, 65 (19.87%) with csPCa, and 38 (11.62%) with clinically insignificant prostate cancer (cisPCa). Prostate-specific antigen density (PSAD), lesion volume (LV), lesion location, and apparent diffusion coefficient (ADC) were found to be independent risk factors for PCa and csPCa in PI-RADS scores 1-3 population. PSAD and lesion location were independent risk factors for PCa in the PI-RADS scores 1-2 population, while PSAD, lesion location and ADC were independent risk factors for PCa in the PI-RADS score 3 population. Four nomograms were established based on these variables. For the population with PI-RADS scores 1-3, the area under the ROC (AUC) for predicting PCa and csPCa was 0.78 and 0.79, respectively. For patients with PI-RADS scores 1-2, the AUC for predicting PCa was 0.75. For patients with PI-RADS score 3, the AUC for predicting PCa was 0.78. The calibration curves revealed good concordance between the predicted probability and the actual probability. DCA demonstrated the net benefit of nomograms. Internal validation revealed strong discrimination of the nomograms.ConclusionWe developed novel nomograms with acceptable discriminability for predicting PCa and csPCa in patients with PSA &lt; 10 ng/ml and PI-RADS score ≤ 3. These models can assist urologists in determining the necessity of prostate biopsy.
BRAF inhibitor monotherapy in BRAFV600E-mutated pediatric low-grade glioma: a single center’s experience
Authors: McThenia S. S. , Reddy K. M. , Damaraju E. , Castellino E. , He Z. , Beer R. , Chien F. , Castellino R. C. , Goldman-Yassen A. E. , Fangusaro J. R. , MacDonald T. 
Published: January 2025

BackgroundPediatric low-grade gliomas (pLGGs) have an overall survival of over 90%; however, patients harboring a BRAFV600E alteration may have worse outcomes, particularly when treated with classic chemotherapy. Combined BRAF/MEK inhibition following incomplete resection demonstrated improved outcome in BRAFV600E altered pLGG compared to combined carboplatin/vincristine chemotherapy and is now considered the standard FDA-approved treatment for this group of tumors. The aim herein was to investigate the efficacy and tolerability of single agent BRAF inhibitor treatment in BRAFV600E altered pLGG.MethodsA single institution retrospective chart review analysis was performed on patients, 0 to 21 years of age, with newly diagnosed and/or progressive BRAFV600E mutated pLGGs (WHO Grade 1 or 2) at Children’s Healthcare of Atlanta treated off-study with BRAF inhibitor monotherapy between 2013-2023. 2-year progression free survival (PFS) and objective tumor response was evaluated. All toxicities possibly associated with BRAF inhibition therapy were evaluated and described according to Common Terminology Criteria for Adverse Events version 5 (CTCAEv5). MRI brain imaging data at baseline and best response was evaluated to identify patterns that may predict response to BRAF inhibition monotherapy.ResultsFifteen patients diagnosed with BRAFV600E mutated pLGG, treated with monotherapy BRAF inhibition, were identified. Median age of diagnosis: 3.8 years (0.2 –18.1). Histologic diagnosis: pilocytic astrocytoma (PA) (N=4); ganglioglioma (GGL) (N=3); GGL, atypical (N=3); pleomorphic xanthroastrocytoma (PXA) (N=2); low-grade neuroepithelial tumor (N=1); infiltrating glioma (N=1); and LGG (NOS) (N=1). Tumor locations included: hypothalamus/optic chiasm (N=6); brainstem (N=4); third ventricle/thalamus (N=2); parietal/temporal lobe (N=2); and spinal cord (N=1). Mean duration of BRAF inhibitor monotherapy: 38.41 months (range 3.9-83.7). Median follow-up: 32.6 months (16 - 78.1). Two-year PFS for patients on BRAFi monotherapy for at least 10 months: 90% (95% CI: 73.2%-100%). Objective Response (OR) for 15 evaluable patients on BRAF inhibitor (BRAFi) therapy: 73% (0/15 CR + 6/15 PR + 5/15 MR) with Overall Response Rate (ORR=CR+PR): 40%. Overall, patients tolerated treatment well with Grade 1 rash being the most common toxicity. Two of 15 patients (13%) discontinued therapy due to toxicities, and 2 other patients switched within drug class from vemurafenib to dabrafenib due to toxicities.DiscussionIn this small cohort of incompletely resected BRAFV600E mutated pLGGs, BRAFi monotherapy was effective and well tolerated with an ORR comparable to published prospective outcomes of dual MEK/BRAF inhibitor therapy. This promising monotherapy treatment should be considered when choosing treatment for incompletely resected BRAFV600E-altered pLGGs.
Survival benefits of adjuvant chemotherapy after conversion surgery in patients with advanced pancreatic cancer
Authors: Lee Yoon Suk , Lee Jang Won , Kim Hak Jun , Chun Jung Won , Lee Jong-Chan , Jang Dong Kee , Hwang Jin-Hyeok , Kim Young Ae , Woo Sang Myung 
Published: January 2025

BackgroundOncologic outcomes of conversion surgery for advanced pancreatic cancer (PC) have scarcely been reported. Therefore, this study aimed to investigate the outcomes of conversion surgery with preoperative treatment of FOLFIRINOX or gemcitabine with nab-paclitaxel (GnP) for patients with advanced PC including locally advanced or metastatic PC.MethodsUsing the National Health Insurance database between 2005 and 2020, we identified patients who underwent conversion surgery after chemotherapy with FOLFIRINOX or GnP for advanced PC. The patients were categorized based on preoperative treatment. Survival outcomes were evaluated based on the date of cancer diagnosis and conversion surgery.ResultsAmong 69,183 patients with advanced PC, 476 underwent conversion surgery; 430 with FOLFIRINOX and 46 with GnP. The median duration from diagnosis to conversion surgery was 6.4 months. Overall survival (OS) was 31.2 months after cancer diagnosis and 23.5 months after conversion surgery. Adjuvant chemotherapy was a significant factor for OS, with hazard ratios (HRs) of 0.23 [95% CI 0.12–0.44, P &lt; 0.01] from cancer diagnosis and 0.20 [95% CI 0.10–0.37, P &lt; 0.01] from conversion surgery. No significant differences were noted between FOLFIRINOX and GnP. However, maintaining the same regimens as preoperative chemotherapy was a significant factor, with HRs of 0.67 [95% CI 0.47–0.95, P = 0.02] from cancer diagnosis and 0.69 [95% CI 0.49–0.98, P = 0.04] from conversion surgery.ConclusionsThe incorporation of adjuvant chemotherapy with the same preoperative regimen could be an effective strategy for patients with advanced PC who would undergo conversion surgery.
Efficacy and safety of nivolumab plus ipilimumab in gastrointestinal cancers: a systematic review and meta-analysis
Authors: Dai Bowen , Jiang Jiaping , Yu Xiaoyu , Zhan Haihua , Hu Zhengchuan 
Published: January 2025

IntroductionGastrointestinal (GI) cancers represent a significant global health burden, and the need for more effective treatment options is exceptionally pressing. The present meta-analysis aimed to explore the efficacy and safety of the combination of nivolumab and ipilimumab in treating GI cancers.MethodsA systematic search of four databases (PubMed, Embase, Web of Science, and Cochrane Library) was conducted for articles on the treatment of GI cancers with nivolumab combined with ipilimumab, published from 2014 up to 30 August 2024. The inclusion criteria were designed according to the principles of Participants, Intervention, Control, Outcomes, and Study (PICOS). The control group was chemotherapy or nivolumab monotherapy or nivolumab in combination with other drugs. We extracted data from 10 randomized controlled trials and utilized a random effects model to assess the objective response rate (ORR), median progression-free survival (mPFS), median overall survival (mOS), median duration of response (mDOR), and treatment-related adverse events (TRAEs). The data analysis was conducted using Review Manager version 5.4 and Stata version 12.0.ResultsOverall, the combination of nivolumab and ipilimumab demonstrated superior outcomes, including a higher ORR (OR = 1.69, P = 0.01), prolonged mOS (MD = 1.74, P = 0.04) and extended mDOR (MD = 5.64, P &lt; 0.00001) compared to the control group. Subgroup analysis demonstrated that the ORR (OR = 1.75, P = 0.02) and mOS (MD = 5.02, P = 0.003) were significantly improved in patients with esophageal cancer. Notably, the ORR in patients with biliary cancer was significantly lower (OR = 0.11, P = 0.04). Additionally, the ORR was significantly higher in the NIVO1 + IPI3group (OR = 2.82, P = 0.01) and NIVO3 + IPI1 group (OR = 1.62, P = 0.01). Regarding safety, there was no statistically significant difference between the combination regimen and the control group in terms of any grade (OR = 0.72, P = 0.26) or grade 3-4 TRAEs (OR = 1.36, P = 0.14).ConclusionsNivolumab in combination with ipilimumab demonstrated significant efficacy in GI cancers (especially esophageal cancer) without causing more adverse reactions. However, its efficacy in biliary cancer still needs to be further proven.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024590994.
Pharmacists’ perceptions of the new pharmaceutical vaccination service in Romania: a comprehensive first two-years evaluation
Authors: Buicu Corneliu-Florin , Naidin Mihaela-Simona , Chereches Marius Calin , Dimulescu Marina-Daniela , Turcu-Stiolica Adina 
Published: January 2025

IntroductionPharmacy-based vaccination services are now available in 56 countries, including Romania, that started administering the flu-vaccines in the community pharmacies from 2022. Assessing how pharmacists managed this new pharmaceutical service in Romania is the subject of this study.MethodsA cross-sectional study was conducted among all the pharmacies from Romania that were authorized to provide this service (442 pharmacies, from which 53 were in rural areas). An online survey was created using Google Forms and included 28 items, with 24 closed-ended questions and 4 open-ended questions. The questionnaire covered six sections: General information, Patient perspective, Authorization and training within the pharmacy, Administration of flu vaccine services, Pharmacy logistics, and Staff satisfaction. Descriptive statistics and chi-squared tests were applied.ResultsIn total, 180 pharmacists participated (response rate was 41%), and the respondents were the pharmacists who administered flu vaccines in these pharmacies. Among the respondents, 92.8% were from urban community pharmacies, and most of them were from Bucharest (26.1%) and East Romania. 88% of respondents considered that this new service will significantly impact the future increase in vaccine coverage rates in Romania. Regarding patients’ perception of this pharmaceutical service (provided by pharmacists), the vaccination service was evaluated very positively by 63% patients and positively by 18% patients, with statistically different perceptions between the types of the pharmacies (p &lt; 0.01). A very positive vaccination evaluation was observed more often among national chain pharmacies (73.1%) rather than among local chain pharmacies (35.9%) or independent pharmacies (36.4%). Regarding logistical barriers, 39% of pharmacies reported no issues with vaccine supply. Moreover, 97% of pharmacies had adequate protective materials to safely administer vaccines. In terms of overall satisfaction, 23% of pharmacists reported being very satisfied, while 39% indicated they were satisfied with the new pharmaceutical service they were providing. The majority (82%) felt that their salaries should be increased related to the vaccination service. Additionally, there is a need for improvements in the pharmacy schedule and the advance scheduling of vaccinations.ConclusionThis study was developed to assist future health policies through expansion of advanced pharmaceutical services, and adding other vaccines to community pharmacy portfolios.