bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of immune checkpoint inhibitors in EGFR-Mutant NSCLC patients with EGFR-TKI resistance: A systematic review and meta-analysis
Authors: Qian Xiaoyu , Guo Xiaodan , Li Ting , Hu Wei , Zhang Lin , Wu Caisheng , Ye Feng 
Published: August 2022

Background: Epidermal growth factor receptor (EGFR) mutations are common in patients with non-small-cell lung cancer (NSCLC), particularly in Asian populations. Tyrosine kinase inhibitors (TKIs) are a first-line treatment in patients with mutant EGFR, but their use is often accompanied by drug resistance, which leads to disease progression. Chemotherapy and immunotherapy are the main treatment options after progression. The efficacy of immune checkpoint inhibitors (ICIs) and their combination therapy in patients with EGFR-TKI resistant is not clear. It is thus necessary to evaluate the efficacy of ICIs and ICI-based combination therapies in patients with EGFR-TKI-resistant NSCLC.Methods: We searched for randomized controlled trials (RCTs) comparing ICI therapy alone or in combination versus other therapies using PubMed, the Cochrane Library, Web of Science, EMBASE, MEDLINE, ClinicalTrials.gov, and several international conference databases, from database inception to 10 March 2022. The hazard ratio (HR) and 95% confidence interval (95% CI) for median overall survival (OS) and median progression-free survival (PFS) were evaluated. Odds ratio (OR), risk ratio (RR), and 95% CI were used as effect indicators for objective response rate (ORR) and safety data.Results: Seven eligible RCTs were included in the present meta-analysis. The results showed that neither ICIs nor combination therapy prolonged median OS in EGFR-TKI resistant NSCLC patients (HR = 1.04, 95% CI: 0.84–1.29, p = 0.73). However, compared with the control group, the patients treated with ICI-based combination therapy had better PFS (HR = 0.62, 95% CI: 0.45–0.86, p = 0.004) and ORR (OR = 1.84, 95% CI: 1.28–2.66, p = 0.001).Conclusion: ICI monotherapy did not improve the OS or PFS of NSCLC patients previously treated with EGFR-TKIs, whereas patients treated with ICI-based combination therapy had better PFS compared with those receiving conventional chemotherapy, indicating that this therapy could be offered to patients with EGFR-mutant NSCLC after progression following TKI treatment. There was no significant difference in all-grade treatment-related adverse events (TRAEs) between the combination therapy group and the control group. However, a higher incidence of discontinuation due to TRAEs was observed; this requires attention in future studies. The results of this meta-analysis provide a reference for clinical practice and future trial design.PROSPERO registration number: CRD42021282207
Dose-dependent reduction of lymphocyte count and heart rate after multiple administration of LC51-0255, a novel sphingosine-1-phosphate receptor 1 modulator, in healthy subjects
Authors: Hwang Inyoung , Lee Sang Won , Oh Jaeseong , Lee SeungHwan , Jang In-Jin , Yu Kyung-Sang 
Published: August 2022

Aim: Sphingosine-1-phosphate receptor mediates the egress of lymphocytes from lymphoid organs, and its inhibition results in a decreased number of circulating lymphocytes. The aim of the current study was to investigate the safety and pharmacodynamic and pharmacokinetic characteristics of a novel sphingosine-1-phosphate receptor modulator, LC51-0255.Methods: A phase 1 randomized, double-blind, placebo-controlled, multiple dosing, dose-escalation study was conducted on healthy Korean male subjects.Results: After single and daily administration of LC51-0255 for 21 days, a dose-dependent decrease in lymphocyte count and heart rate was observed through 0.25–2 mg dose range of LC51-0255. The mean elimination half-life of LC51-0255 was 76–95 h. LC51-0255 was accumulated with a mean accumulation ratio of 5.17–6.64. During the study, LC51-0255 was generally well tolerated. The most common treatment-emergent adverse event was bradycardia. No clinically significant event of arrhythmia, including AV block, was observed. No clinically significant difference in blood pressure was observed between the dose groups. In other safety assessments, no clinically significant abnormalities were observed, except for bradycardia.Conclusion: Daily administration of LC51-0255 in the range of 0.25–2 mg resulted in a dose-dependent reduction of lymphocyte counts and heart rate. LC51-0255 is generally safe and well tolerated in healthy volunteers.
Pharmacokinetics of baicalin and oroxyloside in plasma and different tissues of rats after transnasal aerosol inhalation and intravenous injection of Tanreqing
Authors: Chen Teng-Fei , Song Ling , Gao Yun-Hang , Li Han , Li Jian-Liang , Hou Hong-Ping , Peng Bo , Wang Hui-Ying , Cheng Wen-Hao , Ye Zu-Guang , Li Ying-Fei , Zhang Guang-Ping 
Published: August 2022

To avoid adverse drug reactions associated with injection, off-label nebulization of Tanreqing (TRQ) injection is often used in China to treat respiratory diseases. However, the aerodynamic properties and lung availability of TRQ aerosols remain largely uninvestigated. This study aimed to investigate the size distribution of TRQ aerosols and to compare the pharmacokinetics and tissue distribution of two compounds from TRQ (baicalin and oroxyloside) after transnasal aerosol inhalation and intravenous administration. Furthermore, this study aimed to evaluate the efficacy of TRQ against lipopolysaccharide-induced lung inflammation. The Dv(50) and transmission of TRQ aerosols were 2.512 μm and 74.867%, respectively. The Cmax of baicalin and oroxyloside in rat plasma after inhalation was lower than that after intravenous injection. After inhalation, the area under the curve (AUC) of baicalin and oroxyloside in tissues (lung, bronchoalveolar lavage fluid, and trachea) was 7.9–115.3 and 9.5–16.0 times that observed after intravenous administration, respectively. Baicalin and oroxyloside maintained high concentrations 4 h after inhalation, but only 1 h after intravenous injection. The mean lung-to-plasma concentration ratios of baicalin and oroxyloside were 287.6 and 49.9 times higher than with intravenous administration. Inhaled TRQ achieved the same effect against lipopolysaccharide-induced lung inflammation in mice at doses of only 1/16–1/8 of those administered intravenously. The results indicate that TRQ inhalation is a promising alternative to intravenous injections for the treatment of respiratory infection.
Link of sorafenib resistance with the tumor microenvironment in hepatocellular carcinoma: Mechanistic insights
Authors: Tian Xinchen , Yan Tinghao , Liu Fen , Liu Qingbin , Zhao Jing , Xiong Huabao , Jiang Shulong 
Published: August 2022

Sorafenib, a multi-kinase inhibitor with antiangiogenic, antiproliferative, and proapoptotic properties, is the first-line treatment for patients with late-stage hepatocellular carcinoma (HCC). However, the therapeutic effect remains limited due to sorafenib resistance. Only about 30% of HCC patients respond well to the treatment, and the resistance almost inevitably happens within 6 months. Thus, it is critical to elucidate the underlying mechanisms and identify effective approaches to improve the therapeutic outcome. According to recent studies, tumor microenvironment (TME) and immune escape play critical roles in tumor occurrence, metastasis and anti-cancer drug resistance. The relevant mechanisms were focusing on hypoxia, tumor-associated immune-suppressive cells, and immunosuppressive molecules. In this review, we focus on sorafenib resistance and its relationship with liver cancer immune microenvironment, highlighting the importance of breaking sorafenib resistance in HCC.
Psychophysiological Responses of Exercise Distribution During High Intensity Interval Training Using Whole Body Exercise
Authors: Machado Alexandre F. , Zovico Paulo Vinicios Camuzi , Evangelista Alexandre L. , Rica Roberta L. , Miranda João Marcelo de Q. , Alberton Cristine Lima , Bullo Valentina , Gobbo Stefano , Bergamin Marco , Baker Julien S. , Bocalini Danilo S. 
Published: August 2022

The time-efficient nature of HIIT using bodyweight exercises can facilitate the application of exercise programs at home by encouraging more people to perform regular physical exercise. However, there are no studies investigating the influence of the distribution/order of exercises during HIIT training sessions using this method. The aim of the present study was to evaluate the effects of different exercise orders on training load indicators during HIIT sessions using body weight. Twenty male participants performed three 20-min sessions of HIIT using whole body exercise, consisting of 20 sets with 30 s of activity performed at maximal intensity, followed by 30 s of passive recovery. Three designs of exercise protocols were randomly performed according to the following exercise distribution: A: jumping jack, burpee, mountain climb and squat jump); B: jumping jack, mountain climb, burpee, and squat jump) and C: burpee, squat jump, jumping jack and mountain climb. No differences were found between protocols for relative heart rate, perceived exertion, and lactate concentrations. Significant differences (p &lt; 0.001) were found for the number of movements (A:712 ± 59, B:524 ± 49, C:452 ± 65). No differences were observed for the area under curve when examining perceived exertion between protocols. However, the values for perceived recovery significantly differed (p &lt; 0.001) between protocols (A:64 ± 19; B:52 ± 11; C:17 ± 13). Interestingly, protocol B and C induced a displeasure perception compared to protocol A. Our findings suggest that exercise distribution/order using HIIT whole body exercise promotes alterations in psychophysiological responses in HIIT using whole body exercises.
The effect of subjective life expectancy on the participation in commercial pension insurance of Chinese elderly
Authors: Zhou Mei , Wang Yingyi , Liang Yunjia , Shi Ruonan , Zhao Shaoyang 
Published: August 2022

ObjectiveThis paper studies the impact of the subjective life expectancy of the elderly on their commercial pension insurance participation at micro perspective, providing new evidence to explain the motivation of commercial pension insurance participation in China.MethodsUsing 4 waves of data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018, a multiple linear regression model is constructed to investigate the effect of subjective life expectancy on commercial pension insurance participation among the Chinese elderly, and IV model estimation shows that the results are robust. Meanwhile, the heterogeneity of the effect of elderly life expectancy on commercial pension insurance participation behavior among different characteristic groups is also studied.ResultsA one standard deviation improvement in our measure of subjective life expectancy predicts a 0.9% point higher participation rate in commercial pension insurance. We also find that there is significant heterogeneity in the effects of subjective life expectancy on the participation of elderly people in commercial pension insurance with respect to gender, education, hukou, and wealth.ConclusionThis paper provides a new perspective to explain the factors influencing commercial pension insurance participation in China. We suggest that improving residents’ awareness of life expectancy is beneficial to their reasonable retirement planning, in the background of stepping into an aging society in China.
Individualized assessment of risk and overall survival in patients newly diagnosed with primary osseous spinal neoplasms with synchronous distant metastasis
Authors: Tong Yuexin , Huang Zhangheng , Jiang Liming , Pi Yangwei , Gong Yan , Zhao Dongxu 
Published: August 2022

BackgroundThe prognosis of patients with primary osseous spinal neoplasms (POSNs) presented with distant metastases (DMs) is still poor. This study aimed to evaluate the independent risk and prognostic factors in this population and then develop two web-based models to predict the probability of DM in patients with POSNs and the overall survival (OS) rate of patients with DM.MethodsThe data of patients with POSNs diagnosed between 2004 and 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistics regression analyses were used to study the risk factors of DM. Based on independent DM-related variables, we developed a diagnostic nomogram to estimate the risk of DM in patients with POSNs. Among all patients with POSNs, those who had synchronous DM were included in the prognostic cohort for investigating the prognostic factors by using Cox regression analysis, and then a nomogram incorporating predictors was developed to predict the OS of patients with POSNs with DM. Kaplan–Meier (K-M) survival analysis was conducted to study the survival difference. In addition, validation of these nomograms were performed by using receiver operating characteristic (ROC) curves, the area under curves (AUCs), calibration curves, and decision curve analysis (DCA).ResultsA total of 1345 patients with POSNs were included in the study, of which 238 cases (17.70%) had synchronous DM at the initial diagnosis. K-M survival analysis and multivariate Cox regression analysis showed that patients with DM had poorer prognosis. Grade, T stage, N stage, and histological type were found to be significantly associated with DM in patients with POSNs. Age, surgery, and histological type were identified as independent prognostic factors of patients with POSNs with DM. Subsequently, two nomograms and their online versions (https://yxyx.shinyapps.io/RiskofDMin/ and https://yxyx.shinyapps.io/SurvivalPOSNs/) were developed. The results of ROC curves, calibration curves, DCA, and K-M survival analysis together showed the excellent predictive accuracy and clinical utility of these newly proposed nomograms.ConclusionWe developed two well-validated nomograms to accurately quantify the probability of DM in patients with POSNs and predict the OS rate in patients with DM, which were expected to be useful tools to facilitate individualized clinical management of these patients.
Chemical Composition of Combretum erythrophyllum Leaf and Stem Bark Extracts
Authors: Bantho Sahejna , Naidoo Yougasphree , Dewir Yaser Hassan , Bantho Ayuvna , Murthy Hosakatte Niranjana 
Published: August 2022

Combretaceae is a large Angiosperm family that is highly sought after because of its pronounced medicinal value. Combretum is recognized as the largest genus, prevalent in southern Africa due to its extensive use in traditional medicine. This study aimed to provide a comparative analysis of the phytochemical constituents of the leaf and stembark extracts of Combretum erythrophyllum (Burch.) Sond. Leaf and stembark crude extracts were generated using hexane, chloroform, and methanol as the solvents of choice. Qualitative phytochemical tests indicated the presence of phytocompounds, including carbohydrates, alkaloids, sterols, phenols, fixed oils, and fats. Flavonoids were found within the leaf extracts only, while saponins, mucilage, and gums were specifically identified within the stembark extracts. The first reported gas chromatography–mass spectrometry (GC–MS) screening of C. erythrophyllum leaf and stembark extracts was conducted, yielding the identification of 266 phytocompounds. Major phytocompounds such as sitosterol and lupeol, which may have possible anti-cancer and anti-inflammatory properties, were identified. Furthermore, a pharmacogenetic evaluation was conducted. As a result, both the leaf and stem bark material were seen to fluoresce a wide array of colors (brown, red, green, and blue colorations), indicating the presence of beneficial phytometabolites and their use in medicinal applications. Given the wide array of proposed medicinal benefits associated with the presence of phytocompounds identified within C. erythrophyllum, this species should be considered for its medicinal importance. The isolation and extraction of these beneficial compounds open further avenues for their use in the pharmaceutical industry.
Practical means to forecast potential bankruptcy and financial insolvency of companies
Authors: Alexandrovna-Chernyavskaya Svetlana N , Yuryevna-Roshchektaeva Uliana , Vyacheslavovna-Akasheva Valentina , Ibragimovna-Kitieva Malika , Nikolaevna-Dzodzieva Fatima 
Published: August 2022

The actions of companies are a multifaceted and complex procedure. The company communicates with several factors at various levels, from state to the suppliers. At the same time, in the course of the organization's whole operation, both internal and external ever-changing circumstances impact its actions and performance. That kind of ever-changing ambiance places organizations at risk of an financially unstable position. A company's bankruptcy is a regarded as crisis that needs particular approaches of financial management to surmount that. It appears greatly significant to evaluate the status of the company, take steps to restore solvency, and define the likelihood of bankruptcy. Analysis and assessment of the likelihood of bankruptcy supply an overall evaluation of the company's monetary stability, and a prediction for the future. This study aims to analyze some practical means to forecast companies' potential bankruptcy and financial insolvency. To gratify that aim, monographic, economic-statistical, and abstract-logical methods are considered. Based on the results obtained, to raise the effectiveness of the company's capital, working capital should be normalized through planning the lowest requirement for working capital for all the constituent factors vital for the company’s uninterrupted, and normal operation.
PENGARUH PENGGUNAAN MODEL DISCOVERY LEARNING BERBANTUAN LINGKUNGAN TERHADAP KOMPETENSI KEAHLIAN PESERTA DIDIK SMK DALAM PEMBIAKAN TANAMAN
Authors: Darma Rosdiana 
Published: August 2022

Pembelajaran biologi di SMK SPP Negeri Samarinda pada peserta didik kelas X ditemukan permasalahan atau kendala (1) rendahnya pencapaian ketuntasan hasil belajar peserta didik, (2) kurangnya keterampilan peserta didik dalam kompetensi kejuruan pertanian. Berdasarkan kasus tersebut, salah satu solusi yang dapat dilakukan melalui pengalaman langsung dalam pembelajaran biologi menggunakan model discovery. Supaya peserta didik dapat mudah memahami konsep, dilakukan kegiatan penyelidikan dalam aktivitas pembelajaran yang bermakna. Penelitian ini bertujuan untuk mengetahui efektivitas pembelajaran reproduksi tumbuhan terhadap kompetensi keterampilan peserta didik dalam pembiakan tanaman dengan menggunakan model pembelajaran discovery berbantuan lingkungan. Penelitian ini menggunakan metode eksperimen dengan merujuk pada posttest-only control design, yaitu terdapat dua kelompok yang masing-masing dipilih secara acak (random). Jumlah sampel pada masing-masing kelompok adalah 28 orang. Kelompok pertama merupakan kelompok eksperimen yang akan diberi perlakuan, dan kelompok lain merupakan kontrol. Berdasarkan hasil penelitian dapat disimpulkan bahwa pembelajaran reproduksi tumbuhan dapat meningkatkan aktivitas belajar peserta didik pada kompetensi pengetahuan maupun keterampilan. Selain itu, penggunaan model pembelajaran discovery berbantuan lingkungan dapat meningkatkan efektivitas pembelajaran, berdasarkan hasil nilai signifikansi (2-tailed) 0,000 0,005 pada independent sample t-test SPSS 20. Pembelajaran reproduksi tumbuhan dapat melatih kompetensi keterampilan peserta didik dalam pembiakan tanaman
VALIDITAS PERANGKAT PRAKTIKUM VIRTUAL TERINTEGRASI MODEL PEMBELAJARAN DISCOVERY LEARNING UNTUK MENINGKATKAN KEMAMPUAN BERPIKIR KRITIS SISWA
Authors: Sidabutar Feronika Romauli , Hasan Ani Mustapa , Nusantari Elya 
Published: August 2022

Penelitian ini adalah penelitian pengembangan yang bertujuan untuk menghasilkan perangkat praktikum virtual terintegrasi model pembelajaran Discovery Learning pada materi Bakteri yang memiliki kriteria valid sehingga dapat digunakan dalam proses pembelajaran untuk meningkatkan kemampuan berpikir kritis siswa. Metode yang digunakan dalam penelitian ini yaitu penelitian pengembangan (RD) modifikasi dari Sugiyono (2013). Produk yang dikembangkan adalah Perangkat Praktikum Virtual. RD terdiri dari 10 langkah, tetapi dalam artikel hanya melaporkan 5 tahap sebagai berikut: (1) Potensi dan Masalah; (2) Pengumpulan Data; (3) Desain Produk; (4) Validasi Produk; (5) Revisi Produk. (6) Uji Coba Produk Penelitian ini menggunakan hanya 5 dari 10 langkah dalam model penelitian dan pengembangan (R D) karena menyesuaikan dengan tujuan dari penelitian yang akan diuji. Untuk uji validasi dilakukan dengan mengahadirkan para pakar pada bidangnya yang disebut sebagai validator. Dalam penelitian ini menggunakan 4 validator. Hasil penelitian pengembangan perangkat praktikum virtual menggunakan aplikasi Adobe photoshop cs 6, kevalidan perangkat praktikum virtual terintegrasi model pembelajaran Discovery Learning telah berkategori sangat valid dengan persentase kevalidan media 87%, persentase kevalidan materi 98,7%, persentase kevalidan perangkat pembelajaran 98% dan persentase kevalidan praktisi 96% dengan kategori sangat valid. Berdasarkan hasil penelitian dapat disimpulkan bahwa perangkat praktikum virtual terintegrasi model pembelajaran Discovery Learning pada materi bakteri sangat valid, untuk meningkatkan kemampuan berpikir kritis siswa
Лечение детей с послеоперационными интраабдоминальными инфильтратами
Authors: Мельниченко М.Г. , Антонюк В.В. , Ситникова В.А. , Элий Л.Б. 
Published: August 2022

Цель. Повысить эффективность лечения детей с послеоперационными интраабдоминальными инфильтратами.Материалы и методы. Объектом клинических исследований был аппендикулярный перитонит у 150 детей в возрасте от 2 до 18 лет, находившихся в отделении гнойносептической хирургии Одесской областной детской клинической больницы.Результаты. Разработана программа комплексного лечения послеоперационных интраабдоминальных инфильтратов у детей с аппендикулярным перитонитом путем сочетанного применения медикаментозных и преформированных физических факторов в условиях стационарного и амбулаторного лечения. Доказано, что обнаружение клинических признаков (самостоятельная и спровоцированная боль в животе, пальпируемая «опухоль») свидетельствует о формировании послеоперационного интраабдоминального инфильтрата и его локализации, что требует обязательного комплексного щадящего лечения на всех стадиях возможного аффекта.Выводы. Применение разработанной программы комплексного лечения повысило эффективность лечения и обеспечило хороший результат в 95,1% случаев и отсутствие неудовлетворительного результата.
Purpose. To increase the effectiveness of treatment of children with postoperative intra- abdominal infiltrates.Materials and methods. The object of clinical studies was appendicular peritonitis in 150 children of 2–18 years old, who were in the department of purulent-septic surgery of the Odessa Regional Children’s Clinical Hospital.Results. The program of complex treatment of postoperative intra-abdominal infiltrate in children with appendicular peritonitis by combined use of drug and preformed physical factors under conditions of in-patient and out-patient treatment is developed. It is proved that the detection of clinical signs (independent and provoked abdominal pain, a palpable "tumor") indicates the formation of postoperative intra-abdominal infiltrate and its localization, which requires obligatory comprehensive sparing treatment at all stages of possible affect.Conclusions. The use of the developed program of complex treatment improved effectiveness of treatment and provided a "good" result in 95.1% cases and the absence of an "unsatisfactory" result.