bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-1 inhibitor versus bevacizumab in combination with platinum-based chemotherapy for first-line treatment of advanced lung adenocarcinoma: A retrospective-real world study
Authors: Huang Zhe , Zhou Chunhua , Xiong Yi , Yang Feng , Zeng Fanxu , Jiang Wenjuan , Zhang Yongchang , Yang Haiyan , Liu Li , Zeng Liang , Yang Nong , Wang Zhan 
Published: November 2022

BackgroundChemotherapy combined with immunotherapy or anti-vascular therapy is both recommended by guidelines for first-line treatment of lung adenocarcinoma. However, no head-to-head clinical trial has ever compared which strategy is the optimal choice. This real-world retrospective study was done to compare the efficacy and treatment-related adverse events of immunotherapy and bevacizumab in combination with chemotherapy.Patients and methodsFrom January 2018 to March 2021, we retrospectively collected 276 patients with advanced lung adenocarcinoma managed with chemotherapy combined with bevacizumab or PD-1 inhibitors at our center. Among them, 139 patients were treated with chemotherapy combined with bevacizumab, while 137 patients were treated with chemotherapy combined with PD-1 inhibitors. After receiving four cycles of combination therapy, all patients received maintenance therapy until disease progression. Progression‐free survival (PFS), overall response rate (ORR), overall survival (OS), disease control rate (DCR), and adverse events (AE) were analyzed between the two groups.ResultsCompared to patients who received anti-vascular therapy, patients who underwent immunotherapy achieved better PFS (7.3 months vs. 10 months, p = 0.002) while ORR (40.9% vs. 51.1%, p = 0.093), as well as OS (18 months vs. 24 months, p = 0.060), had no statistical difference between the two groups. In the PD-L1-negative population, there was no statistical difference in PFS and OS between the two groups. (8.0 months VS. 6.0 months, p = 0.738; and 19 months vs. 13 months, p = 0.274). In the PD-L1-positive population, there was a significant benefit in PFS in the population receiving immunotherapy (7.0 months vs. 10.0 months, p = 0.009). Proteinuria and hypertension occurred more frequently in the bevacizumab-treated group (p = 0.001 and p = 0.002), whereas immune-related pneumonia and hypothyroidism occurred more frequently in the immunotherapy-treated group (p = 0.007 and p = 0.030).ConclusionsThe addition of a PD-1 inhibitor was superior to bevacizumab in terms of PFS among patients with advanced lung adenocarcinoma. PD-L1-positive patients appeared to exhibit better PFS, OS, and ORR. Toxic reactions were manageable in both groups.
Cardiovascular effects associated with chimeric antigen receptor T cell therapy in cancer patients: A meta-analysis
Authors: Chen Li-Rong , Li Ya-Jia , Zhang Zheng , Wang Ping , Zhou Tao , Qian Kai , Fan Yu-Xin , Guo Yu , He Gong-Hao , Shen Lei 
Published: November 2022

BackgroundAlthough numerous studies confirmed the marked efficacy of chimeric antigen receptor T cells (CAR-T cells) in many hematologic malignancies, severe cardiovascular toxicities remain to be a major obstacle when incorporating this technology. Furthermore, previous individual investigations regarding the cardiovascular toxicities of CAR-T cell therapy also reported controversial conclusions. Therefore, a meta-analysis was performed to further evaluate the impacts of CAR-T cell therapy on cardiovascular toxicities.MethodsThe PubMed, Embase, Web of Science, and ClinicalTrials.gov databases were searched for eligible studies up to April 2022. All analyses were carried out using the R 4.1.0 software.ResultsEventually, 25 related studies consisting of 2,059 patients were enrolled in the current meta-analysis. We discovered that the pooled incidence rate of the all-cause mortality rate was 14.1% and that the pooled incidence rates of overall cardiovascular (CV) events and CV events with cytokine release syndrome (CRS) grade ≥ 2 were 25.6% and 14.2%, respectively. The pooled incidence of hypotension was 28.6%. Further analysis showed that the incidence rates of arrhythmias, cardiovascular dysfunction, heart failure (HF), CV deaths, acute coronary syndrome (ACS), cardiomyopathy, cardiac arrest, and other CV events were 19.2%, 8.0%, 5.3%, 1.8%, 2.5%, 2.9%, 1.3%, and 1.9%, respectively.ConclusionCancer patients treated with CAR-T cell therapy were at risk for cardiovascular toxicities, of which the most common cardiovascular events were arrhythmias, cardiovascular dysfunction, and heart failure. These findings would contribute to achieving more rational and individualized use of CAR-T cells in clinical treatment.
Pravastatin and placental insufficiency associated disorders: A systematic review and meta-analysis
Authors: Hirsch Ayala , Rotem Reut , Ternovsky Natali , Hirsh Raccah Bruria 
Published: November 2022

Background: Uteroplacental insufficiency associated disorders, such as preeclampsia, fetal growth restriction and obstetrical antiphospholipid syndrome, share pathophysiology and risk factors with cardiovascular diseases treated with statins.Objective: To evaluate pregnancy outcomes among women with uteroplacental insufficiency disorders who were treated with statins.Search Strategy: Electronic databases were searched from inception to January 2022Selection Criteria: Cohort studies and randomized controlled trials.Data collection and analysis: Pooled odds ratios were calculated using a random-effects model; meta-regression was utilized when applicable.Main Results: The analysis included ten studies describing 1,391 women with uteroplacental insufficiency disorders: 703 treated with pravastatin and 688 not treated with statins. Women treated with pravastatin demonstrated significant prolongation of pregnancy (mean difference 0.44 weeks, 95%CI:0.01–0.87, p = 0.04, I2 = 96%) and less neonatal intensive care unit admissions (OR = 0.42, 95%CI: 0.23–0.75, p = 0.004, I2 = 25%). In subgroup analysis, prolongation of pregnancy from study entry to delivery was statistically significant in cohort studies (mean difference 8.93 weeks, 95%CI:4.22–13.95, p = 0.00) but not in randomized control studies. Trends were observed toward a decrease in preeclampsia diagnoses (OR = 0.54, 95%CI:0.27–1.09, p = 0.09, I = 44%), perinatal death (OR = 0.32, 95%CI:0.09–1.13, p = 0.08, I2 = 54%) and an increase in birth weight (mean difference = 102 g, 95%CI: -14–212, p = 0.08, I2 = 96%). A meta-regression analysis demonstrated an association between earlier gestational age at initiation of treatment and a lower risk of preeclampsia development (R2 = 1).Conclusion: Pravastatin treatment prolonged pregnancy duration and improved associated obstetrical outcomes in pregnancies complicated with uteroplacental insufficiency disorders in cohort studies.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/ identifier CRD42020165804 17/2/2020.
The pharmacological mechanism of Chinese herbs effective in treating advanced ovarian cancer: Integrated meta-analysis and network pharmacology analysis
Authors: Yang Ze , Wang Xiang , Hong Wei , Zhang Shiyi , Yang Yang , Xia Yongliang , Yang Ruiwen 
Published: November 2022

Background: Advanced ovarian cancer (AOC) develops rapidly, adding to difficulties in treatment. Traditional Chinese medicine (TCM) plays a significant role in the treatment of AOC, and so to explore the efficacy and safety of TCM in the treatment of AOC and its effective targets, we performed the following review.Methods: The major databases were searched for randomized controlled trials of TCM for the treatment of AOC. A meta-analysis of the efficacy of Chinese herbs on AOC was conducted using RevMan 5.4 software. Active compounds and target genes were acquired using the TCMSP database. The main targets of AOC were obtained through the GenCards, OMIM, TTD, and DrugBank databases. A protein–protein interaction network carried out on the STRING platform was used to select core genes. The Metascape platform was applied to achieve GO and KEGG enrichment analysis.Results: A total of 24 studies were included. Meta-analysis shows the TCM group improved the overall response rate (OR = 2.71; 95% CI = [2.14, 3.44], Z = 8.25, p &lt; 0.00001), overall survival (OR = 2.93, 95% CI = [2.03, 4.24], Z = 5.72, p &lt; 0.00001), and progression-free survival (OR = 5.36, 95% CI = [5.03, 5.69], Z = 31.88, p &lt; 0.00001) of AOC patients, as well as reducing many adverse events. There were 120 compounds, 246 herb target genes, and 1503 disease targets extracted. The 10 most important components were quercetin, kaempferol, 7-methoxy-2-methyl isoflavone, formononetin, isorhamnetin, hederagenin, stigmasterol, luteolin, 7-O-methylisomucronulatol, and calycosin. The 20 core targets were TP53, STAT3, JUN, AKT1, MAPK3, RELA, MAPK1, ESR1, IL6, FOS, MAPK14, TNF, CDKN1A, RB1, CCND1, EGFR, STAT1, MDM2, MAPK8, and CAV1. KEGG enrichment analysis showed that there are many pathways directly related to different types of tumors, such as in pathway cancer and prostate cancer.Conclusion: Our article reveals TCM is effective and safe against AOC and that Chinese herbs exert effects on the disease through multi-target, multi-component, and multi-pathway mechanisms.Systematic Review Registration: (www.crd.york.ac.uk/PROSPERO/), identifier (CRD42022369731).
PD-1 inhibitor-based adverse events in solid tumors: A retrospective real-world study
Authors: Huang Guili , Liu Songqing , Dong Jie , Xi Xin , Kong Rui , Li Wenjun , Du Qian 
Published: November 2022

Background &amp; Aims: Immune checkpoint inhibitors (ICIs) have transformed the landscape of cancer treatment, and ICI-related toxicities (i.e., immune-related adverse events (irAEs) have been reported in many clinical studies. However, the toxicity data of real-world have not been fully assessed.Methods: Patients with histologically confirmed solid tumors who had been treated with PD-1 inhibitors were included in the study. Patient data were collected from electronic medical records, including basic characteristics, data of irAEs, management and outcome. Incidences of irAEs were pooled and compared, and the risk of irAEs was also analyzed.Results: A total of 362 solid tumor patients treated with sintilimab (n = 171), camrelizumab (n = 60), toripalimab (n = 72), and pembrolizumab (n = 59) were included. In total, any grade irAEs, grade 1–2 irAEs, and grade ≥3 irAEs accounted for 47.24%, 38.67% and 8.56% of cases, reapectively. Further, 29.24% of patients discontinued immunotherapy due to irAEs, with pneumonitis being the main reason for discontinuation. By comparing the toxicity profiles between different ICIs, we found that reactive capillary haemangiomas were camrelizumab-specific. Additionally, the frequency of irAEs was association with ICIs type, the pooled incidence (standardized rate) of irAEs related to sintilimab, camrelizumab, toripalimab and pembrolizumab were 55.56% (52.81%), 48.33% (55.55%), 33.33% (29.23%) and 38.98% (38.29%), respectively. Sintilimab and camrelizumab had higher incidences of any grade and grade 1–2 than toripalimab (55.56% vs. 33.33%, p = 0.002; 48.54% vs. 25.00%, p = 0.0001) and pembrolizumab (55.56% vs. 38.98%, p = 0.0028; 48.54% vs. 25.42%, p = 0.002), while the grade ≥3 irAEs of pembrolizumab (13.56%) were approximately 1.63- to 1.93-fold higher than other ICIs, and the standardized grade ≥3 of pembrolizumab was significantly higher than that of sintilimab (13.21% vs. 7.12%, p = 0.026), especially for grade ≥3 pneumonitis. Multivariate analysis found that cumulative cycles of ICI (OR = 1.081; 95% CI: 1.023–1.142; p = 0.006), and lung cancer (OR = 1.765; 95% CI: 1.105–2.820; p = 0.017) were independent risk factors for irAEs.Conclusion: The frequency of irAEs is associated with ICI type. The pooled incidence of irAEs related to sintilimab and pneumonitis caused by pembrolizumab were higher. These data indicate the importance of having different monitoring priorities for different PD-1 inhibitors.
A review of ns-pulsed Raman lasers based on diamond crystal
Authors: Liu Yuxuan , You Wei , Zhu Chengjie , Li Muye , Sun Yuxiang , Yin Xiongfei , Chen Dijun , Feng Yan , Chen Weibiao , Yang Xuezong 
Published: November 2022

High-power ns-pulsed lasers have been widely used in many significant applications, including laser radar, remote-sensing, biomedicine, industrial process, and military defense. Stimulated Raman scattering (SRS) provides an efficient method for extending the wavelengths of laser radiation. Due to the excellent thermal conductivity, high damage threshold, and high gain coefficient, diamond crystal is considered the most potential SRS material to address laser output in specific wavelength regions with high power, high beam quality, and high conversion efficiency. This paper reviews the advances of ns-pulsed crystalline Raman lasers and particularly emphasizes the progress of ns-pulsed diamond Raman lasers (DRLs) in the past decade. DRL has demonstrated a maximum peak power of 1.2 MW at 1.240 μm with a pulse duration of 8 ns. It can also generate high-energy ns pulses featuring Fourier-limited spectral linewidth. The superior optical characteristics and the mature technology of synthetic diamond crystal will make DRL a promising technique to achieve higher performance ns laser pulses.
Automated model calibration with parallel MCMC: Applications for a cardiovascular system model
Authors: Argus Finbar , Zhao Debbie , Babarenda Gamage Thiranja P. , Nash Martyn P. , Maso Talou Gonzalo D. 
Published: November 2022

Computational physiological models continue to increase in complexity, however, the task of efficiently calibrating the model to available clinical data remains a significant challenge. One part of this challenge is associated with long calibration times, which present a barrier for the routine application of model-based prediction in clinical practice. Another aspect of this challenge is the limited available data for the unique calibration of complex models. Therefore, to calibrate a patient-specific model, it may be beneficial to verify that task-specific model predictions have acceptable uncertainty, rather than requiring all parameters to be uniquely identified. We have developed a pipeline that reduces the set of fitting parameters to make them structurally identifiable and to improve the efficiency of a subsequent Markov Chain Monte Carlo (MCMC) analysis. MCMC was used to find the optimal parameter values and to determine the confidence interval of a task-specific prediction. This approach was demonstrated on numerical experiments where a lumped parameter model of the cardiovascular system was calibrated to brachial artery cuff pressure, echocardiogram volume measurements, and synthetic cerebral blood flow data that approximates what can be obtained from 4D-flow MRI data. This pipeline provides a cerebral arterial pressure prediction that may be useful for determining the risk of hemorrhagic stroke. For a set of three patients, this pipeline successfully reduced the parameter set of a cardiovascular system model from 12 parameters to 8–10 structurally identifiable parameters. This enabled a significant(>4×)efficiency improvement in determining confidence intervals on predictions of pressure compared to performing a naive MCMC analysis with the full parameter set. This demonstrates the potential that the proposed pipeline has in helping address one of the key challenges preventing clinical application of such models. Additionally, for each patient, the MCMC approach yielded a 95% confidence interval on systolic blood pressure prediction in the middle cerebral artery smaller than ±10 mmHg (±1.3 kPa). The proposed pipeline exploits available high-performance computing parallelism to allow straightforward automation for general models and arbitrary data sets, enabling automated calibration of a parameter set that is specific to the available clinical data with minimal user interaction.
The effect of high-dietary K+ (HK) on Kir4.1/Kir5.1 and ROMK in the distal convoluted tubule (DCT) is not affected by gender and Cl− content of the diet
Authors: Meng Xin-Xin , Zhang Hao , Meng Gui-Lin , Jiang Shao-Peng , Duan Xin-Peng , Wang Wen-Hui , Wang Ming-Xiao 
Published: November 2022

Basolateral potassium channels in the distal convoluted tubule (DCT) are composed of inwardly-rectifying potassium channel 4.1 (Kir4.1) and Kir5.1. Kir4.1 interacts with Kir5.1 to form a 40 pS K+ channel which is the only type K+ channel expressed in the basolateral membrane of the DCT. Moreover, Kir4.1/Kir5.1 heterotetramer plays a key role in determining the expression and activity of thiazide-sensitive Na-Cl cotransport (NCC). In addition to Kir4.1/Kir5.1, Kir1.1 (ROMK) is expressed in the apical membrane of the late DCT (DCT2) and plays a key role in mediating epithelial Na+ channel (ENaC)-dependent K+ excretion. High dietary-K+-intake (HK) stimulates ROMK and inhibits Kir4.1/Kir5.1 in the DCT. Inhibition of Kir4.1/Kir5.1 is essential for HK-induced suppression of NCC whereas the stimulation of ROMK is important for increasing ENaC-dependent K+ excretion during HK. We have now used the patch-clamp-technique to examine whether gender and Cl− content of K+-diet affect HK-induced inhibition of basolateral Kir4.1/Kir5.1 and HK-induced stimulation of ROMK. Single-channel-recording shows that basolateral 40 pS K+ channel (Kir4.1/Kir5.1) activity of the DCT defined by NPo was 1.34 (1% KCl, normal K, NK), 0.95 (5% KCl) and 1.03 (5% K+-citrate) in male mice while it was 1.47, 1.02 and 1.05 in female mice. The whole-cell recording shows that Kir4.1/Kir5.1-mediated-K+ current of the early-DCT (DCT1) was 1,170 pA (NK), 725 pA (5% KCl) and 700 pA (5% K+-citrate) in male mice whereas it was 1,125 pA, 674 pA and 700 pA in female mice. Moreover, K+-currents (IK) reversal potential of DCT (an index of membrane potential) was -63 mV (NK), −49 mV (5% KCl) and −49 mV (5% K-citrate) in the male mice whereas it was -63 mV, −50 mV and −50 mV in female mice. Finally, TPNQ-sensitive whole-cell ROMK-currents in the DCT2 /initial-connecting tubule (CNT) were 910 pA (NK), 1,520 pA (5% KCl) and 1,540 pA (5% K+−citrate) in male mice whereas the ROMK-mediated K+ currents were 1,005 pA, 1,590 pA and 1,570 pA in female mice. We conclude that the effect of HK intake on Kir4.1/Kir5.1 of the DCT and ROMK of DCT2/CNT is similar between male and female mice. Also, Cl− content in HK diets has no effect on HK-induced inhibition of Kir4.1/Kir5.1 of the DCT and HK-induced stimulation of ROMK in DCT2/CNT.
Attention–deficit/hyperactivity disorder symptoms, perceived stress, and suicidal ideation during the COVID-19 pandemic
Authors: Stickley Andrew , Shirama Aya , Inagawa Takuma , Ruchkin Vladislav , Koposov Roman , Isaksson Johan , Inoue Yosuke , Sumiyoshi Tomiki 
Published: November 2022

ObjectiveAttention–deficit/hyperactivity disorder (ADHD) symptoms have been linked to suicidal behavior. However, little is known about the mechanisms involved in this association. This study examined ADHD symptoms and suicidal ideation during the COVID-19 pandemic and the role of self–perceived stress in this association.MethodData were analyzed from an online sample of 1,452 Japanese individuals aged 18 to 89 obtained in February 2021. Information was collected on past–year suicidal ideation. ADHD symptoms were assessed with the Adult ADHD Self–Report Scale (ASRS) Screener while stress was measured with the Perceived Stress Scale (PSS−14). Depressive symptoms were assessed with the Patient Health Questionnaire (PHQ−9), while the Generalized Anxiety Disorder scale (GAD−7) was used to assess anxiety symptoms. Logistic regression was used to examine associations.ResultsFifty–one (3.5%) individuals had ADHD symptoms, while more than one in ten (11.7%) of the respondents reported past–year suicidal ideation. In an analysis adjusted for sociodemographic factors, ADHD symptoms were associated with eight times higher odds for past–year suicidal ideation. However, adjusting the analysis for mental health variables (anxiety and depressive symptoms) attenuated the association which became non–significant (odds ratio [OR]: 1.96, 95% confidence interval [CI]: 0.92–4.18). In contrast, in an analysis adjusted for mental health, individuals with ADHD symptoms and stress had significantly higher odds for suicidal ideation (OR: 3.72, 95%CI: 1.43–9.67) whereas, ADHD symptoms without stress were not linked to suicidal ideation (OR: 1.25, 95%CI: 0.38–4.18).ConclusionsSelf–perceived stress is important in the association between ADHD symptoms and suicidal ideation among individuals in Japan during the COVID-19 pandemic. Detecting and managing stress and its effects in individuals with ADHD/ADHD symptoms should be a therapeutic focus for improving health–related outcomes in this population both during the COVID-19 pandemic and beyond.
COVID-19-related future anxiety is associated with the health-related quality of life in school-aged children and adolescents—A cross-sectional study
Authors: Kästner Anika , Lücker Petra , Hannich Arne , Schmeyers Lena , Lücker Janny , Hoffmann Wolfgang 
Published: November 2022

BackgroundOver the course of the COVID-19 pandemic, previous studies have shown that the physical as well as the mental health of children and adolescents significantly deteriorated. Future anxiety caused by the COVID-19 pandemic and its associations with quality of life has not previously been examined in school children.MethodsAs part of a cross-sectional web-based survey at schools in Mecklenburg-Western Pomerania, Germany, two years after the outbreak of the pandemic, school children were asked about COVID-19-related future anxiety using the German epidemic-related Dark Future Scale for children (eDFS-K). Health-related quality of life (HRQoL) was assessed using the self-reported KIDSCREEN-10. The eDFS-K was psychometrically analyzed (internal consistency and confirmatory factor analysis) and thereafter examined as a predictor of HRQoL in a general linear regression model.ResultsA total of N = 840 8–18-year-old children and adolescents were included in the analysis. The eDFS-K demonstrated adequate internal consistency reliability (Cronbach's α = 0.77), and the confirmatory factor analysis further supported the one-factor structure of the four-item scale with an acceptable model fit. Over 43% of students were found to have low HRQoL. In addition, 47% of the students sometimes to often reported COVID-19-related fears about the future. Children with COVID-19-related future anxiety had significantly lower HRQoL (B = – 0.94, p &lt; 0.001). Other predictors of lower HRQoL were older age (B = – 0.63, p &lt; 0.001), and female (B = – 3.12, p &lt; 0.001) and diverse (B = – 6.82, p &lt; 0.001) gender.ConclusionTwo years after the outbreak of the pandemic, school-aged children continue to exhibit low HRQoL, which is further exacerbated in the presence of COVID-19-related future anxiety. Intervention programs with an increased focus on mental health also addressing future anxiety should be provided.