bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemo-Immunotherapy Regimes for Recurrent or Metastatic Nasopharyngeal Carcinoma: A Network Meta-Analysis and Cost-Effectiveness Analysis
Authors: Zhu Youwen , Liu Kun , Ding Dong , Wang Kailing , Liu Xiaoting , Tan Xiao 
Published: May 2022

Introduction: In 2021, two phase III clinical trials confirmed that toripalimab or camrelizumab combined with gemcitabine and cisplatin (TGP or CGP) provide more benefits in the first-line treatment of R/M NPC than GP. Fortunately, TGP and CGP were recently approved as first-line treatments for cases experiencing R/M NPC by the China National Medical Products Administration in 2021. However, due to the high cost and variety of treatment options, the promotion of chemo-immunotherapeutics in the treatment of R/M NPC remains controversial. Therefore, we performed a cost-effectiveness assessment of the two newly approved treatment strategies to assess which treatments provide the greatest clinical benefits at a reasonable cost.Methods: A cost-effectiveness analysis and network meta-analysis network meta-analysis was conducted based on the JUPITER-02 and CAPTAIN-first Phase 3 randomized clinical trials. A Markov model was expanded for the evaluation of the effectiveness and cost of TGP, CGP, and GP chemotherapy with a 10-years horizon and measured the health achievements in quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and life-years (LYs). We constructed a treatment strategy and other parameters based on two clinical trials and performed one-way and probabilistic sensitivity experiments for the evaluation of the uncertainty in the model.Results: For the model of patients with treatment-R/M NPC, TGP was associated with a total cost of $48,525 and 2.778 QALYs (4.991 LYs), leading to an ICER of $15,103 per QALY ($10,321 per LY) compared to CGP. On comparing the GP chemotherapy, we found TGP and CGP incurred substantial health costs, resulting in ICERs of $19,726 per QALY and $20,438 per QALY, respectively. The risk of adverse events (AEs) and the price of the drugs had significant impacts on the ICER. At the assumed willingness-to-pay (WTP) threshold of $35,673 per QALY, there were approximately 75.8 and 68.5% simulations in which cost-effectiveness was achieved for TGP and CGP, respectively.Conclusion: From the Chinese payer’s perspective, TGP is more possible to be a cost-effective regimen compared with CGP and GP for first-line treatment of patients with R/M NPC at a WTP threshold of $35,673 per QALY.
The Alleviation of LPS-Induced Murine Acute Lung Injury by GSH-Mediated PEGylated Artesunate Prodrugs
Authors: Hao Dan-Li , Wang Ya-Jie , Yang Jia-Ying , Xie Ran , Jia Ling-Yu , Cheng Jin-Tang , Ma Hai , Tian Ji-Xiang , Guo Shan-Shan , Liu Ting , Sui Feng , Zhao Yu , Chen Yan-Jun , Zhao Qing-He 
Published: May 2022

Acute lung injury (ALI) or its aggravated stage acute respiratory distress syndrome (ARDS) is a common severe clinical syndrome in intensive care unit, may lead to a life-threatening form of respiratory failure, resulting in high mortality up to 30–40% in most studies. Nanotechnology-mediated anti-inflammatory therapy is an emerging novel strategy for the treatment of ALI, has been demonstrated with unique advantages in solving the dilemma of ALI drug therapy. Artesunate (ART), a derivative of artemisinin, has been reported to have anti-inflammatory effects. Therefore, in the present study, we designed and synthesized PEGylated ART prodrugs and assessed whether ART prodrugs could attenuate lipopolysaccharide (LPS) induced ALI in vitro and in vivo. All treatment groups were conditioned with ART prodrugs 1 h before challenge with LPS. Significant increased inflammatory cytokines production and decreased GSH levels were observed in the LPS stimulated mouse macrophage cell line RAW264.7. Lung histopathological changes, lung W/D ratio, MPO activity and total neutrophil counts were increased in the LPS-induced murine model of ALI via nasal administration. However, these results can be reversed to some extent by treatment of ART prodrugs. The effectiveness of mPEG2k-SS-ART in inhibition of ALI induced by LPS was confirmed. In conclusion, our results demonstrated that the ART prodrugs could attenuate LPS-induced ALI effectively, and mPEG2k-SS-ART may serve as a novel strategy for treatment of inflammation induced lung injury.
Safety, Pharmacokinetics/Pharmacodynamics, and Absolute Bioavailability of Dexmedetomidine Hydrochloride Nasal Spray in Healthy Subjects: A Randomized, Parallel, Escalating Dose Study
Authors: Kuang Yun , Wang Sai-Ying , Wang Meng-Na , Yang Guo-Ping , Guo Can , Yang Shuang , Zhang Xing-Fei , Yang Xiao-Yan , Pei Qi , Zou Chan , He Yan-Hong , Zhou Ying-Yong , Duan Kai-Ming , Huang Jie 
Published: May 2022

Background: The present study evaluated the safety, pharmacokinetics/pharmacodynamics (PK/PD), and absolute bioavailability (Fabs) of Dex nasal spray in healthy adult subjects, which serves as a bridge for the subsequent study in children.Methods: Part 1: a double-blind, placebo-controlled, single ascending dose study was performed on 48 subjects. For 20-/40-μg groups, every 6/2 subjects received either Dex/placebo nasal spray or Dex/placebo injection in two periods. In total, 12/4 subjects each received 100 μg Dex/placebo nasal spray. Part 2: a randomized, double-blind, placebo-controlled study; 12/4 subjects received 150 μg Dex/placebo nasal spray. Part 3: a randomized, open, self-crossover study; 12 subjects received 20 μg and 100 μg Dex nasal spray in two periods alternately. The method of administration was optimized in Part 2 and Part 3.Results: In part 1, Dex nasal spray was well tolerated up to the maximum dose of 100 μg, whereas the Fabs was tolerated to only 28.9%–32.3%. In Part 2 and Part 3, the optimized nasal spray method was adopted to promote the Fabs of Dex nasal spray to 74.1%–89.0%. A severe adverse event was found in Part 2. In Part 3 (100 μg), the Ramsay score increased the most and lasted the longest, whereas the BIS score decreased most significantly.Conclusion: Using the optimized nasal spray method, a single dose of 20/100 μg of the test drug was safe and tolerable, and 100 μg may have approached or reached the plateau of sedation. In addition, it is found that the optimized method can greatly improve the bioavailability of the test drug, leading to its higher reference value.
Croton urucurana Baill. Ameliorates Metabolic Associated Fatty Liver Disease in Rats
Authors: Auth Pablo Alvarez , da Silva Gustavo Ratti , Amaral Eduarda Carolina , Bortoli Victor Fajardo , Manzano Mariana Inocencio , de Souza Lauro Mera , Lovato Evellyn Claudia Wietzikoski , Ribeiro-Paes João Tadeu , Gasparotto Junior Arquimedes , Lívero Francislaine Aparecida dos Reis 
Published: May 2022

Background: Metabolic associated fatty liver disease (MAFLD) affects a quarter of the worldwide population, but no drug therapies have yet been developed. Croton urucurana Baill. (Euphorbiaceae) is a medicinal species, that is, widely distributed in Brazil. It is used in popular medicine to treat gastrointestinal, cardiovascular, and endocrine system diseases. However, its hepatoprotective and lipid-lowering effects have not yet been scientifically investigated.Aim of the study: The present study investigated the effects of an extract of C. urucurana in a rat model of MAFLD that was associated with multiple risk factors, including hypertension, smoking, and dyslipidemia.Material and Methods: The phytochemical composition of C. urucurana was evaluated by liquid chromatography-mass spectrometry. Spontaneously hypertensive rats received a 0.5% cholesterol-enriched diet and were exposed to cigarette smoke (9 cigarettes/day for 10 weeks). During the last 5 weeks, the animals were orally treated with vehicle (negative control [C-] group), C. urucurana extract (30, 100, and 300 mg/kg), or simvastatin + enalapril (two standard reference drugs that are commonly used to treat dyslipidemia and hypertension, respectively). One group of rats that were not exposed to these risk factors was also evaluated (basal group). Blood was collected for the analysis of cholesterol, triglyceride, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. The liver and feces were collected for lipid quantification. The liver was also processed for antioxidant and histopathological analysis.Results: The main constituents of the C. urucurana extract were flavonoids, glycosides, and alkaloids. The model successfully induced MAFLD, reflected by increases in AST and ALT levels, and induced oxidative stress in the C- group. Treatment with the C. urucurana extract (300 mg/kg) and simvastatin + enalapril decreased plasma and hepatic lipid levels. In contrast to simvastatin + enalapril treatment, C. urucurana reduced AST and ALT levels. Massive lesions were observed in the liver in the C- group, which were reversed by treatment with the C. urucurana extract (300 mg/kg).Conclusion:C. urucurana extract exerted promising hepatoprotective and lipid-lowering effects in a preclinical rat model of MAFLD.
Wavelength-Tunable Kerr-Lens Mode-Locked Femtosecond Cr:ZnS Laser With a ∼300-nm Tuning Range From 2.2 to 2.5 μm
Authors: Wang Qing , Wang Runyu , Yang Fan , Li Yan 
Published: May 2022

Tunable 2∼3-μm femtosecond lasers are of high interest in various applications, such as medical diagnostics and molecular spectroscopy. Cr:ZnSe/ZnS is extremely suited for broadband tunable femtosecond lasers due to its excellent emission bands. In this article, we demonstrate a wavelength-tunable Kerr-lens mode-locked Cr:ZnS laser by utilizing a birefringent filter. The group delay dispersion of the operation and the thickness of the birefringent are finely optimized. With the rotation of the birefringent filter, the scheme offers a tuning bandwidth of over 300 nm from 2,220 nm to 2,520 nm. To the best of our knowledge, it is the broadest tuning range among the reported femtosecond Cr:ZnS lasers.
Extracellular Inflammasome Particles Are Released After Marathon Running and Induce Proinflammatory Effects in Endothelial Cells
Authors: Kogel Alexander , Fikenzer Sven , Uhlmann Luisa , Opitz Lena , Kneuer Jasmin M. , Haeusler Karl Georg , Endres Matthias , Kratzsch Jürgen , Schwarz Viktoria , Werner Christian , Kalwa Hermann , Gaul Susanne , Laufs Ulrich 
Published: May 2022

Objectives: The intracellular NLRP3 inflammasome is an important regulator of sterile inflammation. Recent data suggest that inflammasome particles can be released into circulation. The effects of exercise on circulating extracellular apoptosis-associated speck-like protein (ASC) particles and their effects on endothelial cells are not known.Methods: We established a flow cytometric method to quantitate extracellular ASC specks in human serum. ASC specks were quantitated in 52 marathon runners 24–72 h before, immediately after, and again 24–58 h after the run. For mechanistic characterization, NLRP3 inflammasome particles were isolated from a stable mutant NLRP3 (p.D303N)-YFP HEK cell line and used to treat primary human coronary artery endothelial cells.Results: Athletes showed a significant increase in serum concentration of circulating ASC specks immediately after the marathon (+52% compared with the baseline, p &lt; 0.05) and a decrease during the follow-up after 24–58 h (12% reduction compared with immediately after the run, p &lt; 0.01). Confocal microscopy revealed that human endothelial cells can internalize extracellular NLRP3 inflammasome particles. After internalization, endothelial cells showed an inflammatory response with a higher expression of the cell adhesion molecule ICAM1 (6.9-fold, p &lt; 0.05) and increased adhesion of monocytes (1.5-fold, p &lt; 0.05).Conclusion: These findings identify extracellular inflammasome particles as novel systemic mediators of cell–cell communication that are transiently increased after acute extensive exercise with a high mechanical muscular load.
Association of Hemoglobin Glycation Index With Contrast-Induced Acute Kidney Injury in Patients Undergoing Coronary Angiography: A Retrospective Study
Authors: Chen Zhezhe , Li Duanbin , Lin Maoning , Jiang Hangpan , Xu Tian , Shan Yu , Fu Guosheng , Wang Min , Zhang Wenbin 
Published: May 2022

Background: The hemoglobin glycation index (HGI) quantifies interindividual variation in glycation and is positively associated with cardiovascular diseases. However, the association between HGI and contrast-induced acute kidney injury (CI-AKI) remains unclear. Therefore, this study aimed to assess the association of HGI with CI-AKI.Methods: In this observational study, a total of 3,142 patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) were included. The HGI was calculated as the difference between the measured glycated hemoglobin (HbA1c) and predicted HbA1c. CI-AKI was defined as an increase of either 25% or 0.5 mg/dl (44.2 μmol/L) in the serum creatinine (SCr) level within 72 h following the exposure to contrast medium. Piecewise linear regression analysis was conducted to testify the association of HGI with the proportion of SCr elevation. Modified Poisson’s regression analysis was performed to determine the association between HGI and CI-AKI. Exploratory analysis was also performed according to the stratification of HbA1c levels.Results: Among 3,142 patients, the average age was 66.9 years and 483 of them (15.4%) suffered CI-AKI. Piecewise linear regression analysis demonstrated the linear association of HGI with the proportion of SCr elevation on both positive and negative sides of HGI [HGI &lt;0: β = −9.537, 95% CI (−12.057 to −7.017), p &lt; 0.001; HGI ≥0: β = 1.655, 95% CI (0.125 to 3.186), p = 0.034]. Modified Poisson’s regression analysis showed that the higher absolute value of HGI was strongly associated with higher incidence of CI-AKI [(&lt;−1.0 vs. −0.2 to 0.2): aRR = 1.897, 95% CI [1.467 to 2.452], p &lt; 0.001 (≥1.0 vs. −0.2 to 0.2): aRR = 1.545, 95% CI (1.171 to 2.037), p = 0.002]. Furthermore, the results in exploratory analysis showed that such association still remained irrespective of HbA1c levels.Conclusion: The higher absolute value of HGI was strongly associated with higher incidence of CI-AKI in patients undergoing CAG and PCI.
S-Thyroid Computer-Aided Diagnosis Ultrasound System of Thyroid Nodules: Correlation Between Transverse and Longitudinal Planes
Authors: Yang Keen , Chen Jing , Wu Huaiyu , Tian Hongtian , Ye Xiuqin , Xu Jinfeng , Luo Xunpeng , Dong Fajin 
Published: May 2022

Introduction: We compare the differences in the diagnostic results of S-thyroid, a computer-aided diagnosis (CAD) software, based on two mutually perpendicular planes.Methods: Initially, 149 thyroid nodules confirmed by surgical pathology were enrolled in our study. CAD in our study was based on the ACR TI-RADS lexicon. t test, rank-sum test, and Chi-square test were used. The interclass correlation coefficient and Cohen’s kappa were used to explore the correlation between CAD features. Receiver operating characteristic was plotted for different combinations of CAD features.Results: The patient’s age, transverse diameter, longitudinal diameter, shape, margin, echogenicity, echogenic foci, composition, TI-RADS classification, and risk probability of nodules in the transverse and longitudinal planes were related to thyroid cancer (p &lt; 0.05). The AUC (95%CI) of TI-RADS classification in the transverse plane of CAD is better than that of the longitudinal plane [0.90 (0.84–0.95) vs. 0.83 (0.77–0.90), p = 0.04]. The AUC (95%CI) of risk probability of nodules in the transverse planes shows no difference from that in the longitudinal plane statistically [0.90 (0.85–0.95) vs. 0.88 (0.82–0.94), p = 0.52]. The AUC (95% CI), specificity, sensitivity, and accuracy [TI-RADS classification (transverse plane) + TI-RADS classification (longitudinal plane) + risk (transverse plane) + risk (longitudinal plane)] are 0.93 (0.89–0.97), 86.15%, 90.48%, and 88.59%, respectively.Conclusion: The diagnosis of thyroid cancer in the CAD transverse plane was superior to that in the CAD longitudinal plane when using the TI-RADS classification, but there was no difference in the diagnosis between the two planes when using risk. However, the combination of CAD transverse and longitudinal planes had the best diagnostic ability.
Urinary Metabolomic Study in a Healthy Children Population and Metabolic Biomarker Discovery of Attention-Deficit/Hyperactivity Disorder (ADHD)
Authors: Tian Xiaoyi , Liu Xiaoyan , Wang Yan , Liu Ying , Ma Jie , Sun Haidan , Li Jing , Tang Xiaoyue , Guo Zhengguang , Sun Wei , Zhang Jishui , Song Wenqi 
Published: May 2022

ObjectivesKnowledge of the urinary metabolomic profiles of healthy children and adolescents plays a promising role in the field of pediatrics. Metabolomics has also been used to diagnose disease, discover novel biomarkers, and elucidate pathophysiological pathways. Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in childhood. However, large-sample urinary metabolomic studies in children with ADHD are relatively rare. In this study, we aimed to identify specific biomarkers for ADHD diagnosis in children and adolescents by urinary metabolomic profiling.MethodsWe explored the urine metabolome in 363 healthy children aged 1–18 years and 76 patients with ADHD using high-resolution mass spectrometry.ResultsMetabolic pathways, such as arachidonic acid metabolism, steroid hormone biosynthesis, and catecholamine biosynthesis, were found to be related to sex and age in healthy children. The urinary metabolites displaying the largest differences between patients with ADHD and healthy controls belonged to the tyrosine, leucine, and fatty acid metabolic pathways. A metabolite panel consisting of FAPy-adenine, 3-methylazelaic acid, and phenylacetylglutamine was discovered to have good predictive ability for ADHD, with a receiver operating characteristic area under the curve (ROC–AUC) of 0.918. A panel of FAPy-adenine, N-acetylaspartylglutamic acid, dopamine 4-sulfate, aminocaproic acid, and asparaginyl-leucine was used to establish a robust model for ADHD comorbid tic disorders and controls with an AUC of 0.918.
A Scoping Review of Gender Differences in Suicide in India
Authors: Ramesh Parvathy , Taylor Peter J. , McPhillips Rebecca , Raman Rajesh , Robinson Catherine 
Published: May 2022

IntroductionMuch of the published literature on suicide comes from high income countries. In countries such as India, female suicide rates exceed the global suicide rate and suicide rates found in their male counterparts. Results from previous studies indicate that factors related to suicide among men and women in India are different from those seen in high-income countries. To date, no reviews have considered the relationship between gender and suicide in India. Therefore, the aim of this scoping review is to provide a comprehensive understanding of existing literature reporting gender differences in suicide rates, methods, risk factors and antecedent factors in India by reviewing published studies.MethodA scoping review was conducted to map the existing literature on gender differences in suicide in India. To identify peer-reviewed publications, online databases PsycINFO and Embase were searched. The search terms were [suicid*AND India*]. The searches took place in November 2020 and May 2021, with no language restrictions. Articles published from 2014 onwards from India were included. Reference lists of selected studies were searched for studies that could meet the inclusion criteria.ResultsThis review identified 17 studies that met the inclusion criteria. The ratio between women and men who die by suicide in India is much lower than in high-income countries. Hanging was found to be a more commonly used method of suicide among both men and women, in comparison to high-income countries where hanging is more common among men. This review also identified several gaps in the literature. There were few studies that examined suicide among transgender Indians. There was limited literature on gender differences in risk and protective factors for suicide. Limitations such as the omission of a lack of gender-based analyses in several studies and under-reporting of suicide rates were identified.ConclusionUnderstanding suicide within the context of individual countries is essential in designing culture-appropriate suicide prevention strategies. This review identified an urgent need to establish and evaluate suicide surveillance systems in India. Furthermore, additional research is warranted to understand suicide among individuals who identify outside the gender binary, and gender-specific risk and protective factors.
Development and Feasibility Testing of the Clinical-Community Linkage Self-Assessment Survey for Community Organizations
Authors: Fishleder Sarah , Harris Jeffrey R. , Petrescu-Prahova Miruna , Kohn Marlana , Helfrich Christian D. 
Published: May 2022

IntroductionClinical-community linkages (CCLs) can improve health, but few instruments exist to evaluate these partnerships. To address this gap, we develop and test the Clinical-Community Linkage Self-Assessment Survey (CCL Self-Assessment).Materials and MethodsWe built on an existing framework and conducted a literature review to guide the design of our survey, and obtained feedback from academic, clinical, and community-based experts. To pretest the instrument, we conducted 10 think-aloud interviews with community-based health-promotion organizations. We performed feasibility testing with 38 staff from 20 community organizations, followed by criterion-validity testing.ResultsThe 15-item final instrument includes five domains: Nature of the Relationship, Communication, Referral Process, Feedback Loop, and Timeliness. Expert feedback included keeping the CCL Self-Assessment brief and actionable. Think-aloud interviews produced a range of revisions related to item wording, instructions, brevity, and formatting. Feasibility testing showed high response rate and ease of administration. Sites scoring high on the CCL Self-Assessment also scored high on the criterion measure.DiscussionWe demonstrate feasibility, as well as face, content, construct, and criterion validity. Initial results suggest the CCL Self-Assessment survey may be used by community organizations to identify strengths and weaknesses of their linkages. Next steps include additional statistical validation and testing to determine how the CCL Self-Assessment survey works in the field as well as providing specific tools to improve linkages.
Emotional Intelligence and Burnout Among Otorhinolaryngology–Head and Neck Surgery Residents
Authors: Sharaf Abdulelah M. , Abdulla Isra H. , Alnatheer Abdullah M. , Alahmari Aghadir N. , Alwhibi Omar A. , Alabduljabbar Ziyad , Alhamzah Hamzah , Alkholaiwi Feras M. 
Published: May 2022

BackgroundBurnout syndrome is common among surgical residents, negatively affecting their mental health, physical wellbeing, and work performance. We investigated the relationship between emotional intelligence (EI) and burnout among Otorhinolaryngology–Head and Neck surgery residents.MethodsThis cross-sectional study examined 51 residents across different Otorhinolaryngology-Head and Neck surgery programs at various hospitals in Saudi Arabia using a survey conducted between January 2021 and March 2021. The questionnaire had different validated measurements of burnout and included the Trait EI Questionnaire–Short Form, Maslach Burnout Inventory–Human Services survey, and questions regarding demographics and job satisfaction.ResultsOf all the residents, 17.6% had a high risk of burnout, 39.2% had emotional exhaustion (EE), 29.4% had depersonalization (DP), and 43.1% had a low sense of personal accomplishment (PA). A statistically significant negative association was observed between the total EI score and EE (r = −0.577, p &lt; 0.001) and DP (r = −0.765, p &lt; 0.001), indicating that higher total EI scores were associated with lower EE levels.ConclusionsPositive associations existed between high levels of EI, PA, and satisfaction with both surgical skills and specialty choice. Therefore, residency programs should use EI modifiers as tools to reduce the risk of burnout.