bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of anti-cancer therapies on lymphocyte subpopulations of lung cancer patients
Authors: Gessner Philipp , Tessema Belay , Scholz Markus , Sack Ulrich , Boldt Andreas , Kühnapfel Andreas , Gessner Christian 
Published: August 2023

IntroductionThere are limited data on the influence of different anti-cancer therapies on lymphocyte subpopulations and their relationships to survival of non-small cell lung cancer (NSCLC) patients. This study aimed to assess the effect of immunotherapy, chemotherapy, immunochemotherapy, adjuvant chemotherapy after surgery, and antibodies against Vascular Endothelial Growth Factors (VEGF) on B cell, T cell, and NK cell subpopulations, and the survival time of NSCLC patients.MethodsA total of 32 consecutive NSCLC patients were recruited at Pulmonology Clinic, Leipzig from January 2018 to March 2020 and enrolled in this study. Immunophenotyping was done using a FACS Canto II flow cytometer (BD Biosciences) before the administration of the planned therapy and during therapy with up to 7 observational windows for each patient targeting 130 immunologic parameters.ResultsAbsolute transitional B cells was significantly increased after immunotherapy (p = 0.032), immunochemotherapy (p = 0.030), and antibodies against VEGF (p = 0.024). Similarly, absolute counts and percentage of B cells were significantly increased after adjuvant chemotherapy (p = 0.023). However, absolute counts and percentage of transitional B cells are significantly decreased after chemotherapy (p = 0.001). Activated cytotoxic T cells were significantly increased after immunotherapy (p = 0.031) and immunochemotherapy (p = 0.030). The overall survival rate of NSCLC patients was 31%.ConclusionsIn conclusion, this study suggests that different types of anti-cancer therapies affect lymphocyte subpopulations of NSCLC patients. Further large-scale and multicentre studies are required to confirm our results and to evaluate the prognostic value of lymphocyte subpopulations.
PTCH1 and CTNNB1 emerge as pivotal predictors of resistance to neoadjuvant chemotherapy in ER+/HER2- breast cancer
Authors: Ozcan Gulnihal 
Published: August 2023

IntroductionEndeavors in the molecular characterization of breast cancer opened the doors to endocrine therapies in ER+/HER2- breast cancer, increasing response rates substantially. Despite that, taxane-based neoadjuvant chemotherapy is still a cornerstone for achieving breast-conserving surgery and complete tumor resection in locally advanced cancers with high recurrence risk. Nonetheless, the rate of chemoresistance is high, and deselecting patients who will not benefit from chemotherapy is a significant task to prevent futile toxicities. Several multigene assays are being used to guide decisions on chemotherapy. However, their development as prognostic assays but not predictive assays limits predictive strength, leading to discordant results. Moreover, high costs impediment their use in developing countries. For global health equity, robust predictors that can be cost-effectively incorporated into routine clinical management are essential.MethodsIn this study, we comprehensively analyzed 5 GEO datasets, 2 validation sets, and The Cancer Genome Atlas breast cancer data to identify predictors of resistance to taxane-based neoadjuvant therapy in ER+/HER2- breast cancer using efficient bioinformatics algorithms.ResultsGene expression and gene set enrichment analysis of 5 GEO datasets revealed the upregulation of 63 genes and the enrichment of CTNNB1-related oncogenic signatures in non-responsive patients. We validated the upregulation and predictive strength of 18 genes associated with resistance in the validation cohort, all exhibiting higher predictive powers for residual disease and higher specificities for ER+/HER2- breast cancers compared to one of the benchmark multi-gene assays. Cox Proportional Hazards Regression in three different treatment arms (neoadjuvant chemotherapy, endocrine therapy, and no systemic treatment) in a second comprehensive validation cohort strengthened the significance of PTCH1 and CTNNB1 as key predictors, with hazard ratios over 1.5, and 1.6 respectively in the univariate and multivariate models.DiscussionOur results strongly suggest that PTCH1 and CTNNB1 can be used as robust and cost-effective predictors in developing countries to guide decisions on chemotherapy in ER +/HER2- breast cancer patients with a high risk of recurrence. The dual function of PTCH1 as a multidrug efflux pump and a hedgehog receptor, and the active involvement of CTNNB1 in breast cancer strongly indicate that PTCH1 and CTNNB1 can be potential drug targets to overcome chemoresistance in ER +/HER2- breast cancer patients.
Clinical outcomes of liposomal irinotecan in advanced pancreatic adenocarcinoma patients previously treated with conventional irinotecan-based chemotherapy: a real-world study
Authors: Gupta Amol , De Jesus-Acosta Ana , Zheng Lei , Lee Valerie , Kamel Ihab , Le Dung , Pishvaian Michael , Laheru Daniel 
Published: August 2023

BackgroundThe efficacy of combination chemotherapy beyond the first-line setting remains modest in patients with advanced pancreatic adenocarcinoma (PAC). Evidence from recent clinical studies has shown that liposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU) and leucovorin (LV) resulted in survival benefits in patients with advanced pancreatic adenocarcinoma (APAC) after progression on gemcitabine-based treatment. However, the survival benefits of nal-IRI in the third and later lines, in which limited options are available, have yet to be extensively studied. Also, some studies have shown conflicting results regarding the impact of prior treatment with conventional IRI on patient outcomes following treatment with nal-IRI. Therefore, this real-world study aimed to evaluate the efficacy and safety of nal-IRI plus 5FU-LV in advanced PAC patients who progressed on conventional IRI-containing regimens.MethodsA retrospective chart review was conducted between November 2016 to December 2022 on 30 patients diagnosed with advanced PAC who completed at least one cycle of nal-IRI plus 5-FU- LV and were previously treated with conventional IRI. Data regarding survival outcomes were retrieved.ResultsThirty patients met the inclusion criteria. Overall, 76.7% of the patients received at least two lines of therapy prior to nal-IRI. The median overall duration of nal-IRI treatment was 2.0 months (IQR: 1.3 – 3.9 months). One patient (3.3%) had a partial response, and seven patients (23.3%) had stable disease as their best response. The median progression-free survival (PFS) was 1.9 months (95% CI 1.6 - 2.0) and the 6-month PFS rate was 20.0%. The median overall survival (OS) was 5.0 months (95% CI 3.4 – 7.0), and the 6-month OS rate was 36.7%. An interval between conventional IRI and nal-IRI ≥5.5 months was significantly associated with prolonged OS of 10.2 months (95% CI 3.3 – 12.1) versus 4.3 months (95% CI 2.1 – 5.9; p =0.003). Ten patients (33.3%) experienced grade 3 adverse events, most commonly nausea, fatigue, diarrhea, and non-neutropenic fever.ConclusionNal-IRI plus 5FU/LV had modest survival benefits and an acceptable safety profile in patients with prior conventional IRI. A longer interval between conventional IRI and nal-IRI was associated with increased survival outcomes.
Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats
Authors: Guo Xiying , Lei Min , Zhao Jiangyan , Wu Min , Ren Zhanhong , Yang Xiaosong , Ouyang Changhan , Liu Xiufen , Liu Chao , Chen Qingjie 
Published: August 2023

Background: One of the typical symptoms of diabetes mellitus patients was memory impairment, which was followed by gradual cognitive deterioration and for which there is no efficient treatment. The anti-diabetic incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were demonstrated to have highly neuroprotective benefits in animal models of AD. We wanted to find out how the GLP-1/GIP dual agonist tirzepatide affected diabetes’s impairment of spatial learning memory.Methods: High fat diet and streptozotocin injection-induced diabetic rats were injected intraperitoneally with Tirzepatide (1.35 mg/kg) once a week. The protective effects were assessed using the Morris water maze test, immunofluorescence, and Western blot analysis. Golgi staining was adopted for quantified dendritic spines.Results: Tirzepatide significantly improved impaired glucose tolerance, fasting blood glucose level, and insulin level in diabetic rats. Then, tirzepatide dramatically alleviated spatial learning and memory impairment, inhibited Aβ accumulation, prevented structural damage, boosted the synthesis of synaptic proteins and increased dendritic spines formation in diabetic hippocampus. Furthermore, some aberrant changes in signal molecules concerning inflammation signaling pathways were normalized after tirzepatide treatment in diabetic rats. Finally, PI3K/Akt/GSK3β signaling pathway was restored by tirzepatide.Conclusion: Tirzepatide obviously exerts a protective effect against spatial learning and memory impairment, potentially through regulating abnormal insulin resistance and inflammatory responses.
Efficacy and safety of combined Chinese and Western medicine in the treatment of knee osteoarthritis: a prospective, multicenter cohort study
Authors: Ye Qian-Yun , Lin Qing , Hu Xue-Ling , Yang Yu-Mei , Zheng Bao-Lin , Li Ting , Zhong Wen-Qiang , Wang Hao-Yu , Zhang Zhi-Fen , Luo Bing-Jie , Xiao Ya-Wen , Wu Ai-Ling , Li Yan , Zou Zhuo-Ling , Li Ling-Yu , Li Xiao-Yun , Wang Pan-Pan , Yang Li , Zhu Xiao-Feng , Han Li , Zhang Rong-Hua 
Published: August 2023

Purpose: To conduct a real-world evaluation of the efficacy and safety of combined Chinese and Western medicine in treating knee osteoarthritis (KOA).Methods: A multicenter, prospective cohort study design was employed, enrolling 450 KOA patients (Kellgren-Lawrence score of 3 or less). The patients were divided into a Western medicine treatment group (WM group) and a combined Western and traditional Chinese medicine treatment group (WM-CM group). A 6-week treatment plan was administered, and follow-up visits occurred at 2 weeks, 4 weeks, and 6 weeks after initiating treatment. The primary outcome indicator was the total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score after 6 weeks of treatment. Secondary outcome indicators included WOMAC subscales for pain, stiffness, and joint function, visual analogue scale (VAS) score, physical component summary (PCS), mental component summary (MCS), and clinical effectiveness. The incidence of drug-related adverse events was used as a safety evaluation indicator.Results: A total of 419 patients were included in the final analysis: 98 in the WM group and 321 in the WM-CM group. The baseline characteristics of the two groups were comparable, except for the incidence of stiffness symptoms and stiffness scores. After 6 weeks of treatment, the WM-CM group exhibited superior results to the WM group in improving the total WOMAC score (24.71 ± 1.38 vs. 16.36 ± 0.62, p &lt; 0.001). The WM-CM group also outperformed the WM group in WOMAC pain and joint function scores, VAS score, PCS score, MCS score, and clinical effectiveness (p &lt; 0.05), which was consistent with the findings of the main evaluation index. Subgroup analysis indicated that the combined Chinese and Western medicine treatment showed more pronounced benefits in patients under 65 years of age and in those with a Kellgren-Lawrence (K-L) classification of 0-I. Throughout the study, no adverse effects were observed in either group.Conclusion: The combination of Chinese and Western medicine demonstrated superiority over Western medicine alone in relieving knee pain symptoms, improving knee function, and enhancing the quality of life for KOA patients with a K-L score of 3 or less. Moreover, the treatment exhibited a good safety profile.Clinical Trial Registration: (https://www.chictr.org.cn/), identifier (ChiCTR1900027175).
Establishment of a sensitive UPLC-MS/MS method to quantify safinamide in rat plasma
Authors: Wang Ying , Zhao Guan-An , Li Xia , Zhang En , Tan Wei , Chen Jia-qi 
Published: August 2023

A fast, simple, and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established for the quantification of safinamide in rat plasma. Plasma samples were treated with acetonitrile for protein precipitation, and diazepam was used as an internal standard (IS). The analytes were separated on an Acquity UPLC C18 (2.1 mm × 50 mm, 1.7 μm) chromatographic column with gradient elution using a mobile phase (0.1% formic acid-acetonitrile). Then, the eluates were detected by electrospray ionization (ESI) in positive ion mode. The analytes were quantified by multiple reaction monitoring (MRM) using the transition m/z 303.3→215.0 of safinamide and m/z 285.0→154.0 of IS. Safinamide had good linearity in the concentration range of 1.0–2000 ng/mL, and the lower limit of quantitation (LLOQ) was 1.0 ng/mL. The intra- and inter-day precision and accuracy of safinamide were less than 7.63%, while the average recovery rate was 92.98%–100.29%. The method was validated to be stable and had low noise, short chromatographic run time, wide linear range, small sample volumes, low sample injection volumes, and high sensitivity. Therefore, it can be used in pharmacokinetics and preclinical and clinical studies.
SeriesSleepNet: an EEG time series model with partial data augmentation for automatic sleep stage scoring
Authors: Lee Minji , Kwak Heon-Gyu , Kim Hyeong-Jin , Won Dong-Ok , Lee Seong-Whan 
Published: August 2023

Introduction: We propose an automatic sleep stage scoring model, referred to as SeriesSleepNet, based on convolutional neural network (CNN) and bidirectional long short-term memory (bi-LSTM) with partial data augmentation. We used single-channel raw electroencephalography signals for automatic sleep stage scoring.Methods: Our framework was focused on time series information, so we applied partial data augmentation to learn the connected time information in small series. In specific, the CNN module learns the time information of one epoch (intra-epoch) whereas the bi-LSTM trains the sequential information between the adjacent epochs (inter-epoch). Note that the input of the bi-LSTM is the augmented CNN output. Moreover, the proposed loss function was used to fine-tune the model by providing additional weights. To validate the proposed framework, we conducted two experiments using the Sleep-EDF and SHHS datasets.Results and Discussion: The results achieved an overall accuracy of 0.87 and 0.84 and overall F1-score of 0.80 and 0.78 and kappa value of 0.81 and 0.78 for five-class classification, respectively. We showed that the SeriesSleepNet was superior to the baselines based on each component in the proposed framework. Our architecture also outperformed the state-of-the-art methods with overall F1-score, accuracy, and kappa value. Our framework could provide information on sleep disorders or quality of sleep to automatically classify sleep stages with high performance.
Psychiatric emergency department visits during the coronavirus disease-2019 pandemic
Authors: Sun HaiMing , Liu HaiChun , Ma ChunYan , Chen Zheng , Wei YanYan , Tang XiaoChen , Xu LiHua , Hu YeGang , Xie YuOu , Chen Tao , Lu Zheng , Wang JiJun , Zhang TianHong 
Published: August 2023

BackgroundPrevious research has demonstrated the negative impact of the coronavirus disease-2019 (COVID-19) pandemic on mental health.AimsTo examine changes in the Chinese psychiatric emergency department (PED) visits for mental health crises that occurred during the pandemic.MethodsBefore and during the COVID-19 pandemic, PED visit counts from the largest psychiatric hospital in China between 2018 and 2020 were investigated. Electronic medical records of 2020 PED visits were extracted during the COVID-19 pandemic period and compared for the same period of 2018 and 2019.ResultsOverall, PED visits per year increased from 1,767 in 2018 to 2210 (an increase of 25.1%) in 2019 and 2,648 (an increase of 49.9%) in 2020. Compared with 2 years before the epidemic, during the COVID-19 pandemic, the proportion of PED visits among patients with stress disorders, sleep disorders, and anxiety disorders increased significantly. In terms of the distribution of demographic characteristics, age shows a younger trend, while the gender difference is not significant.ConclusionThese findings suggest that PED care-seeking increases during the COVID-19 pandemic, highlighting the need to integrate mental health services for patients with stress, sleep, anxiety, and obsessive-compulsive disorders during public health crises.
Tackling Vaccine Hesitancy and Increasing Vaccine Willingness Among Parents of Unvaccinated Children in Austria
Authors: Lenart Christian , Prager Marlene , Sachs Marlene , Steininger Christoph , Fernandes Charlene , Thannesberger Jakob 
Published: August 2023

Objectives: In autumn 2021, there was a surge of COVID-19 infections in Austria, and vaccination coverage stagnated at a below-average level compared to the rest of Europe. Surveys showed that both children and adolescents were the main drivers of the rising infection rates and that vaccination numbers were particularly low in this age group. This was due to widespread vaccination skepticism and hesitancy among parents of unvaccinated children and adolescents.Methods: Here, we describe a novel intervention concept that allowed us to efficiently tackle parental vaccine hesitancy. We designed an intervention series that followed a reproducible format based on online face-to-face seminars in groups of a maximum of twenty people. Each seminar included an anonymous online questionnaire for internal quality control. Moreover, we assessed the motives of parental vaccine hesitancy and asked participants to rate subjective vaccine willingness for their children on a scale of zero to ten.Results: Within 8 weeks, more than 580 people participated in the seminar series. We found that concerns about the side effects of the vaccine were the predominant motive of vaccination hesitancy among the study population. Overall, the intervention could successfully increase the median parental vaccination willingness of participants from a score of five to eight. We identified tree hesitancy motives (distrust towards the pharmaceutical industry, the government, or feelings of restriction from personal freedom) that were associated with below-average vaccination willingness and significant lower increase.Conclusion: With this study we analyzed motives driving COVID-19 vaccination hesitancy among parents of unvaccinated children and reasons of parents to restrain their children from getting vaccinated. The intervention method described here, could effectively address individual concerns on a personal level while at the same time reach a large number of people across geographical and language barriers. Thereby we could significantly increase subjective vaccination willingness of the participants. Our approach is easy to apply, highly cost-effective, and can be used to tackle any kind of medical misinformation.
Le projet de flottage des bois d'Évreux en 1725
Authors: Belhoste Jean-François 
Published: August 2023

Le projet d'un canal au long de l'Iton pour le flottage des bois d'Evreux vers Paris et Rouen, formulé dès 1725, procède de l'accroissement des besoins de Paris en bois pour le chauffage et l'artisanat. L'extension de la zone d'approvisionnement de Paris fait en général reculer les forges, d'où de graves conflits, qu'il est nécessaire de neutraliser. En outre, comme le bois est taxé en ville, son transport doit être bon marché ; c'est pourquoi le flottage s'impose.
Le duc de Bouillon, propriétaire du Comté d'Evreux, possède de très grandes forêts. Il en fait abattre les futaies, qui se reconstituent en taillis, ce qui le place dans la dépendance des maîtres de forges du Pays d'Ouche. Pour échapper à leurs ententes, il souhaite vendre ses bois à Paris et fait étudier le projet du canal de l'Iton en 1725.
Des experts calculent prix de revient et bénéfices. L'essentiel du coût de transport (80%) est lié à la remontée de la Seine. Un dossier technique précis est établi pour le flottage et l'emprise du canal, dont le coût total doit dépasser 81 .000 livres.
Le projet suscite l'opposition de tous les riverains : seigneurs, meuniers et marchands. L'intérêt de la sidérurgie locale, menacée de ruine, prévaut. L'Intendant bloque le projet et les bois restent aux mains des maîtres de forges. Le canal, finalement construit vers 1750, sert seulement au transport des bois de marine et non à l'approvisionnement de Paris
L'approvisionnement en bois de chauffage d'une capitale provinciale au XVIIIe siècle : le cas de Besançon
Authors: Vion-Delphin François 
Published: August 2023

During the 18th century, heating in Besançon was one of the city Magistrate's greatest concerns, a concern as well for the province's Intendant. In order to satisfy ever-increasing demand linked to the city population's doubling in size during the century (from 17,000 inhabitants in 1709 to 32,000 in 1791), municipal forestry property was highly insufficient and timber had to be brought in from the outside. Routes were not designed for regular transportation of heavy timber convoys, and therefore the Doubs river was used to float cut timber upstream.
From 1701 to 1726, numerous conflicts opposed the «Grand-Maitre des Eaux et Forets» and the Intendant ; the «Grand Maitre» feared that the communities of upper Besançon would damage their forest land in order to send larger quantities of wood for heating purposes, while the Intendant, supported by the urban Magistrate, was concerned with insuring a regular supply, and thus avoiding public complaint. This serious problem was resolved between 1726 and 1735 by the decision to use timber from communities of the Val de la Barbeche for urban heating, as well as timber from communities of the entire Baume area. This wood was auctioned by the Grand-Maitre for the communities' profit, with the buyers responsible for floating the logs on the Doubs toward the timber port of Rivotte, at Besançon. River currents were studied in order to facilitate passage and each year, more than 1000 hectares were thus destined for Besançon heating. Difficulties were not totally resolved, however, and at the end of the century, the city still did not benefit from adequate reserves, in the event of an extremely rude winter ; this question of supply remained a major concern up through the 19th century.
Price Prediction Using Web Scraping and Machine Learning Algorithms in the Used Car Market
Authors: YILMAZ Seda , SELVİ İhsan Hakan 
Published: August 2023

The development of technology increases data traffic and data size day by day. Therefore, it has become very important to collect and interpret data. This study, it is aimed to analyze the car sales data collected using web scraping techniques by using machine learning algorithms and to create a price estimation model. The data needed for analysis was collected using Selenium and BeautifulSoup and prepared for analysis by applying various data preprocessing steps. Lasso regression and PCA analysis were used for feature selection and size reduction, and the GridSearchCV method was used for hyperparameter tuning. The results were evaluated with machine learning algorithms.
Random Forest, K-Nearest Neighbor, Gradient Boost, AdaBoost, Support Vector and XGBoost regression algorithms were used in the analysis. The obtained analysis results were evaluated together with Mean Square Error (MSE), Root Mean Square Error (RMSE) and Coefficient of Determination (R-square). When the results for data set 1 were examined, the model that gave the best results was XGBoost Regression with 0.973 R2, 0.026 MSE and 0.161 RMSE values. When the results for data set 2 were examined, the model that gave the best results was K-Nearest Neighbor Regression with 0.978 R2, 0.021 MSE and 0.145 RMSE values.