bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Response Assessment in Advanced Stage Melanoma Treated with Combination Ipilimumab/Nivolumab
Authors: Ma Vincent T. , Chamila Perera Alahendra A. , Sun Yilun , Sitto Merna , Waninger Jessica J. , Warrier Govind , Green Michael D. , Fecher Leslie A. , Lao Christopher D. 
Published: July 2022

BackgroundStandard combination ipilimumab/nivolumab (I/N) is given as 4 induction doses for advanced stage melanoma followed by nivolumab single-agent maintenance therapy. While many patients receive less than 4 doses due to immune-related toxicities, it is unclear if fewer doses of I/N may still provide long term clinical benefit. Our aim is to determine if response assessment after 1 or 2 doses of I/N can predict long-term survival and assess if fewer doses of I/N can lead to similar survival outcomes.MethodsWe performed a retrospective analysis on a cohort of patients with advanced melanoma who w0ere treated with standard I/N. Cox regression of progression-free survival (PFS) and overall survival (OS) models were performed to assess the relationship between response after 1 or 2 doses of I/N and risk of progression and/or death. Clinical benefit response (CBR) was assessed, defined as SD (stable disease) + PR (partial response) + CR (complete response) by imaging. Among patients who achieved a CBR after 1 or 2 doses of I/N, a multivariable Cox regression of survival was used to compare 1 or 2 vs 3 or 4 doses of I/N adjusted by known prognostic variables in advanced melanoma.Results199 patients were evaluated. Patients with CBR after 1 dose of I/N had improved PFS (HR: 0.16, 95% CI 0.08-0.33; p&lt;0.001) and OS (HR: 0.12, 0.05-0.32; p&lt;0.001) compared to progressive disease (PD). Patients with CBR (vs PD) after 2 doses of I/N also had improved PFS (HR: 0.09, 0.05-0.16; p&lt;0.001) and OS (HR: 0.07, 0.03-0.14; p&lt;0.001). There was no survival risk difference comparing 1 or 2 vs 3 or 4 doses of I/N for PFS (HR: 0.95, 0.37-2.48; p=0.921) and OS (HR: 1.04, 0.22-4.78; p=0.965).ConclusionsEarly interval imaging with response during induction with I/N may be predictive of long-term survival in advanced stage melanoma. CBR after 1 or 2 doses of I/N is associated with favorable survival outcomes, even in the setting of fewer I/N doses received. Further studies are warranted to evaluate if electively administering fewer combination I/N doses despite tolerance in select patients may balance the benefits of therapy while decreasing toxicities.
Essential Oils From Five Local Plants: An Alternative Larvicide for Anopheles gambiae s.l. (Diptera: Culicidae) and Aedes aegypti (Diptera: Culicidae) Control in Western Burkina Faso
Authors: Balboné Mahamoudou , Soma Dieudonné Diloma , Namountougou Moussa , Drabo Samuel Fogné , Konaté Hamadou , Toe Oumarou , Bayili Koama , Meda Georges Benson , Dabiré Roch Kounbobr , Gnankine Olivier 
Published: July 2022

IntroductionMalaria and dengue are two main vector-borne infectious diseases transmitted by Anopheles gambiae and Aedes aegypti, respectively, in tropical and subtropical regions. The concern for environmental safety and the increasing development of resistance to the chemical in main arthropod vectors raises interest in the search for botanicals such as essential oils (EOs) that can be used in vector control.MethodsLarvicidal bioassays were performed according to the WHO standard methods using Ae. aegypti and An. gambiae larvae collected from Bobo-Dioulasso and in the Kou Valley (VK), respectively, two areas located in Houet Province of western Burkina Faso. Kisumu and Bora bora, the susceptible strains of An. gambiae and Ae. aegypti, respectively, were used as controls. OEs extracted from leaves of five aromatic plants, Cymbopogon citratus, Cymbopogon nardus, Eucalyptus camaldulensis, Lippia multiflora, and Ocimum americanum, naturally growing in Burkina Faso were tested. The pyriproxyfen was used as a positive control.ResultsAs a result, the lethal concentrations (LC50) for Ae. aegypti from Bobo-Dioulasso and An. gambiae from VK ranged from 41.9 to 103.8 ppm and 39.5 to 138.1 ppm, respectively. As for LC90 values, they ranged from 74.6 to 311.3 ppm for Ae. aegypti from Bobo-Dioulasso and from 90.2 to 328.9 ppm for An. gambiae from VK. Among the EOs tested, L. multiflora showed the highest activity against all the strains of An. gambiae and Ae. aegypti larvae. No difference in terms of LC50 values was found between L. multiflora and pyriproxyfen used as a positive control on An. gambiae larvae. It is not the case for Aedes aegypti populations, where pyriproxyfen remains the most toxic. Overall, An. gambiae populations were the most susceptible to EOs tested as compared to Ae. aegypti populations.ConclusionOur study furthers our knowledge of the larvicidal activity of EOs in the western part of Burkina and opens new avenues in their putative use in vector control strategies.
Association of Exercise With Vascular Function in Patients With CKD: A Meta-Analysis of Randomized Controlled Trials
Authors: Wang Huan , Xie Dengpiao , Wu Lisheng , Zhao Liangbin 
Published: July 2022

Background and AimVascular function is associated with an increased risk of cardiovascular events in patients with chronic kidney disease (CKD). Whether exercise improves vascular function in such patients remains controversial. This study aimed to conduct a meta-analysis on the effect of exercise training on the vascular function of patients with CKD.MethodsEmbase, the Cochrane Central Register of Controlled Trials, and Medline were searched from inception until November 15, 2021. The terms exercise, CKD, dialysis, kidney transplant, and randomized controlled trial (RCT) were searched alone or in combination. RCTs were included when studies compared exercise with active control, usual care, or no intervention, and the studies reported vascular function on patients with CKD.ResultsThis meta-analysis included 18 RCTs with 817 patients. Exercise training was significantly associated with decreased pulse wave velocity weighted mean difference (WMD), −0.56; 95% confidence interval (CI), −1.02 to −0.09, P = 0.02 and augmentation index (WMD, −3.26; 95% CI, −5.46 to −1.05, P = 0.004). It was also significantly associated with improved peak VO2 (WMD, 2.64; 95% CI, 1.94–3.35, P &lt; 0.00001), general health (WMD, 7.03; 95% CI, 0.65–13.42, P = 0.03), and vitality (WMD, 9.1; 95% CI, 2.50–15.69, P = 0.007).ConclusionsThe meta-analysis suggested that exercise training improved vascular function in patients with CKD. An exercise program should be considered as one of the management strategies for vascular dysfunction in patients with CKD. Further studies are needed to demonstrate that exercise training improves cardiovascular diseases in patients with CKD.
Appendicular Skeletal Muscle Index and HbA1c Evaluate Liver Steatosis in Patients With Metabolic Associated Fatty Liver Disease
Authors: Jin Rui , Wang Xiaoxiao , Li Xiaohe , Yang Jia , Liu Baiyi , Wei Lai , Liu Feng , Rao Huiying 
Published: July 2022

Background and Aim(s)Liver steatosis, as the main feature of metabolic associated fatty liver disease (MAFLD), was associated with the progression of liver fibrosis and metabolic syndrome, which needed to be estimated accurately. In this study, we explored the significance of appendicular skeletal muscle index (ASMI) in evaluating liver steatosis of MAFLD patients.MethodsEight hundred and ninety-nine cases with MAFLD from 2017 to 2018 National Health and Nutrition Examination Surveys (NHANES) database were included. All the analyzed data were obtained from NHANES database. The association between ASMI and liver steatosis were evaluated using R and EmpowerStats.ResultsMAFLD individuals were randomly divided into a training (n = 450) and validation cohort (n = 449). In univariate analysis, HbA1c, arms fat, arms lean mass, legs lean mass, trunk lean mass, total fat, total lean mass and ASMI were significantly associated with liver steatosis (p &lt; 0.05). Multivariate analysis showed that HbA1c (OR: 1.6732; 95% CI: 1.2753–2.1929, p = 0.0002) and ASMI (OR: 1.6723; 95% CI: 1.1760–2.5204, p = 0.0052) were independently associated with severe liver steatosis. ASMI accurately evaluated severe liver steatosis with an AUROC of 0.73 and 0.81 in training and validation cohort, respectively. Compared with ASMI only, ASMI combined with HbA1c improved the AUROC to 0.85 and 0.88. Furthermore, the AUROC of our model was superior to FLI in the evaluation of liver steatosis.ConclusionASMI combined with HbA1c has good evaluation value for liver steatosis in MAFLD patients, which might be beneficial for the management of MAFLD clinically.
Bone Specific Alkaline Phosphatase and Serum Calcification Propensity Are Not Influenced by Etelcalcetide vs. Alfacalcidol Treatment, and Only Bone Specific Alkaline Phosphatase Is Correlated With Fibroblast Growth Factor 23: Sub-Analysis Results of the ETACAR-HD Study
Authors: Dörr Katharina , Hödlmoser Sebastian , Kammer Michael , Reindl-Schwaighofer Roman , Lorenz Matthias , Reiskopf Bianca , Jagoditsch Rahel , Marculescu Rodrig , Oberbauer Rainer 
Published: July 2022

Secondary hyperparathyroidism in chronic kidney disease poses a major risk factor for vascular calcification and high bone turnover, leading to mineralization defects. The aim was to analyze the effect of active vitamin D and calcimimetic treatment on fibroblast growth factor 23 (FGF23), serum calcification propensity (T50), a surrogate marker of calcification stress and bone specific alkaline phosphatase (BAP) in hemodialysis. This is a subanalysis of a randomized trial comparing etelcalcetide vs. alfacalcidol in 62 hemodialysis patients for 1 year. We compared the change of BAP and serum calcification propensity between the two medications and assessed the influence of FGF23 change over time. We found no significant differences in the change of BAP or serum calcification propensity (T50) levels from baseline to study end between treatment arms (difference in change of marker between treatment with etelcalcetide vs. alfacalcidol: BAP : 2.0 ng/ml [95% CI-1.5,5.4], p = 0.3; T50: –15 min [95% CI –49,19], p = 0.4). Using FGF23 change over time, we could show that BAP levels at study end were associated with FGF23 change (–0.14 [95% CI –0.21, –0.08], p &lt; 0.001). We did not observe the same association between FGF23 change and T50 (effect of FGF23 change on T50: 3.7 [95% CI –5.1, 12], p = 0.4; R2 = 0.07 vs. R2 = 0.06). No significant difference was found in serum calcification propensity (T50) values between treatment arms. FGF23 was not associated with serum calcification propensity (T50), but was negatively correlated with BAP underlying its role in the bone metabolism.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT03182699].
Prognostic Role of Lymphocyte-C-Reactive Protein Ratio in Colorectal Cancer: A Systematic Review and Meta Analysis
Authors: He Xinglong , Su Ade , Xu Yongcheng , Ma Diaolong , Yang Guoyuan , Peng Yiyun , Guo Jin , Hu Ming , Ma Yuntao 
Published: July 2022

IntroductionThe lymphocyte-C-reactive protein ratio (LCR) is a new immunoinflammatory score and prognostic marker, but the relationship between this index and the prognosis of colorectal cancer patients remains controversial.Therefore, aim of the study was to assess the relationship between LCR and prognosis for colorectal cancer patients through a systematic evaluation and meta-analysis.MethodsWe systematically searched PubMed, EMBASE, Web of Science, and Cochrane Library databases for randomized controlled studies and observational studies on the relationship between LCR and prognosis of colorectal cancer patients, all searched from the date of database creation to January 6, 2022.Our primary endpoints observed were overall survival (OS) and disease-free survival (DFS) of colorectal cancer patients, and secondary observables were basic characteristics of included studies, such as country, study duration, sample size, LCR threshold, and pathological characteristics of patients in each study, such as degree of differentiation, gender, tumor location, T stage, and lymphatic metastasis.ResultsA total of 10 case-control studies including 7068 patients were included. Meta-analysis results showed that overall survival (OS) and disease-free survival (DFS) were worse in colorectal cancer patients with lower levels of LCR (HR=0.44, 95% CI=0.38-0.52, P&lt;0.001; HR=0.56, 95% CI=0.41-0.76, P&lt; 0.001).Subgroup analysis based on country, study length, sample size, and LCR threshold showed that lower levels of LCR were all associated with poorer OS (P &lt; 0.05). Regarding pathological characteristics, patients in the low LCR group were generally poorly differentiated (OR=1.79, 95% CI=1.55-2.07, P&lt;0.001), while there was no significant relationship with gender, tumor location, T stage, and lymphatic metastasis (P&gt;0.05).Discussion/ConclusionLCR can be used as a prognostic marker for colorectal cancer patients, and patients with lower levels of LCR may have a poor prognosis. Due to the limitation of the number and quality of the included studies, the above findings need to be validated by more high-quality studies.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022296563.
Trends in Research of Prenatal Stress From 2011 to 2021: A Bibliometric Study
Authors: Dong Yankai , Chen Shengquan , Wang Zhifei , Ma Yao , Chen Jinfeng , Li Ge , Zhou Jiahao , Ren Yating , Ma Hengyu , Xie Juanping , Li Hui , Zhu Zhongliang 
Published: July 2022

BackgroundMaternal stress during pregnancy can raise the risk of mental disorders in offspring. The continuous emergence of clinical concepts and the introduction of new technologies are great challenges. In this study, through bibliometric analysis, the research trends and hotspots on prenatal stress (PS) were explored to comprehend clinical treatments and recommend future scientific research directions.MethodsStudies on PS published on the Web of Science Core Collection (WoSCC) database between 2011 and 2021 were reviewed. Bibliometric analysis was conducted according to the number of publications, keywords, journals, citations, affiliations, and countries. With the data collected from the WoSCC, visualization of geographic distribution; clustering analysis of keywords, affiliations, and authors; and descriptive analysis and review of PS were carried out.ResultsA total of 7,087 articles published in 2011–2021 were retrieved. During this period, the number of publications increased. Psychoneuroendocrinology is the leading journal on PS. The largest contributor was the United States. The University of California system was leading among institutions conducting relevant research. Wang H, King S, and Tain YL were scholars with significant contributions. Hotspots were classified into four clusters, namely, pregnancy, prenatal stress, oxidative stress, and growth.ConclusionThe number of studies on PS increased. Journals, countries, institutions, researchers with the most contributions, and most cited articles worldwide were extracted. Studies have mostly concentrated on treating diseases, the application of new technologies, and the analysis of epidemiological characteristics. Multidisciplinary integration is becoming the focus of current development. Epigenetics is increasingly used in studies on PS. Thus, it constitutes a solid foundation for future clinical medical and scientific research.
Tongluo Yishen Decoction Ameliorates Renal Fibrosis via NLRP3-Mediated Pyroptosis In Vivo and In Vitro
Authors: Jia Qi , Zhang Xiaoyu , Hao Gaimei , Zhao Yun , Lowe Scott , Han Lin , Qin Jianguo 
Published: July 2022

Purpose: In this study, we investigated the mechanism of Tongluo Yishen (TLYS) decoction in more detail, from the perspective of pyroptosis in the unilateral ureteral ligation (UUO) model and the hypoxia-induced renal tubular epithelial (NRK-52E) cell.Method: The UUO model was used, and after 14 days of TLYS intervention, rats were tested for blood creatinine and urea nitrogen, HE staining was used to observe the pathological changes in the kidney, Masson staining was used to assess the degree of interstitial fibrosis, western blot was used to detect the changes of α-smooth muscle actin (α-SMA) protein expression level, immunohistochemistry and western blot detected the changes in protein expression levels of NOD-like receptor protein 3 inflammasome (NLRP3), gasdermin D (GSDMD), cysteinyl aspartate specific proteinase (caspase-1), interleukin 18 (IL-18) and interleukin 1β (I L-1β). A hypoxia model was created using NRK-52E cell, and after different concentrations of TLYS decoction intervention, the changes in the expression levels of pyroptosis were used with immunofluorescence and western blot methods.Results: TLYS decoction improved renal function, delayed the advancement of renal interstitial fibrosis, and inhibited pyroptosis in UUO rats. Furthermore, we observed that TLYS can mitigate hypoxia-induced NRK-52E cell damage via the suppression of the NLRP3-mediated pyroptosis.Conclusion: TLYS decoction exert renoprotective effects by inhibiting NLRP3-mediated pyroptosis.
Persistent dyspnea after COVID-19 is not related to cardiopulmonary impairment; a cross-sectional study of persistently dyspneic COVID-19, non-dyspneic COVID-19 and controls
Authors: Beaudry Rhys I. , Brotto Andrew R. , Varughese Rhea A. , de Waal Stephanie , Fuhr Desi P. , Damant Ronald W. , Ferrara Giovanni , Lam Grace Y. , Smith Maeve P. , Stickland Michael K. 
Published: July 2022

Background: Up to 53% of individuals who had mild COVID-19 experience symptoms for &gt;3-month following infection (Long-CoV). Dyspnea is reported in 60% of Long-CoV cases and may be secondary to impaired exercise capacity (VO2peak) as a result of pulmonary, pulmonary vascular, or cardiac insult. This study examined whether cardiopulmonary mechanisms could explain exertional dyspnea in Long-CoV.Methods: A cross-sectional study of participants with Long-CoV (n = 28, age 40 ± 11 years, 214 ± 85 days post-infection) and age- sex- and body mass index-matched COVID-19 naïve controls (Con, n = 24, age 41 ± 12 years) and participants fully recovered from COVID-19 (ns-CoV, n = 14, age 37 ± 9 years, 198 ± 89 days post-infection) was conducted. Participants self-reported symptoms and baseline dyspnea (modified Medical Research Council, mMRC, dyspnea grade), then underwent a comprehensive pulmonary function test, cardiopulmonary exercise test, exercise pulmonary diffusing capacity measurement, and rest and exercise echocardiography.Results: VO2peak, pulmonary function and cardiac/pulmonary vascular parameters were not impaired in Long- or ns-CoV compared to normative values (VO2peak: 106 ± 25 and 107 ± 25%predicted, respectively) and cardiopulmonary responses to exercise were otherwise normal. When Long-CoV were stratified by clinical dyspnea severity (mMRC = 0 vs mMRC≥1), there were no between-group differences in VO2peak. During submaximal exercise, dyspnea and ventilation were increased in the mMRC≥1 group, despite normal operating lung volumes, arterial saturation, diffusing capacity and indicators of pulmonary vascular pressures.Interpretation: Persistent dyspnea after COVID-19 was not associated with overt cardiopulmonary impairment or exercise intolerance. Interventions focusing on dyspnea management may be appropriate for Long-CoV patients who report dyspnea without cardiopulmonary impairment.
The Effect of Acute Intermittent and Continuous Hypoxia on Plasma Circulating ßOHB Levels Under Different Feeding Statuses in Humans
Authors: Marcoux Caroline , Morin Renée , Mauger Jean-François , Imbeault Pascal 
Published: July 2022

Introduction: Acute hypoxia is known to increase circulating nonesterified fatty acid (NEFA) levels. Adipose tissue lipolysis is a major source of NEFA into circulation and insulin suppresses this process when the tissue is insulin sensitive. NEFA can be esterified to triglycerides and/or completely/partially oxidized, the latter leading to ketogenesis in the liver. To our knowledge, the effect of hypoxia on ketogenesis, more specifically ß-hydroxybutyrate (ßOHB) levels, remains unknown in humans. Therefore, the objective of this study was to determine the effect of acute intermittent and continuous hypoxia on circulating ßOHB levels under different feeding status.Methods: Plasma samples from three different randomized crossover studies were assessed for ßOHB concentrations. In the first study, 14 healthy men (23 ± 3.5 years) were exposed to 6 h of normoxia or intermittent hypoxia (IH-Fed) (15 hypoxic events/hour) following an isocaloric meal. In the second study, 10 healthy men (26 ± 5.6 years) were exposed to 6 h of continuous normobaric hypoxia (CH-Fasted) (FiO2 = 0.12) or normoxia in the fasting state. In the third study (CH-Fed), 9 healthy men (24 ± 4.5 years) were exposed to 6 h of normoxia or CH in a constant prandial state. ßOHB, NEFA and insulin levels were measured during all sessions.Results: In the IH-Fed study, ßOHB and NEFA levels tended to be greater over 6 h of IH (condition × time interaction, ßOHB p = 0.108 and NEFA p = 0.062) compared to normoxia. In the CH-Fasted study, ßOHB and NEFA levels increased over time in both experimental conditions, this effect being greater under CH (condition × time interaction, ßOHB p = 0.070; NEFA p = 0.046). In the CH-Fed study, ßOHB levels slightly increased up to 180 min before falling back to initial concentrations by the end of the protocol in both normoxia and CH (main effect of time, p = 0.062), while NEFA were significantly higher under CH (p = 0.006).Conclusion: Acute normobaric hypoxia exposure tends to increase plasma ßOHB concentrations over time in healthy men. The stimulating effect of hypoxia on plasma ßOHB levels is however attenuated during postprandial and prandial states.
Developing a Smoking Cessation Intervention for People With Severe Mental Illness Treated by Flexible Assertive Community Treatment Teams in the Netherlands: A Delphi Study
Authors: Küçükaksu Müge H. , Hoekstra Trynke , Jansen Lola , Vermeulen Jentien , Adriaanse Marcel C. , van Meijel Berno 
Published: July 2022

BackgroundThere is still limited evidence on the effectiveness and implementation of smoking cessation interventions for people with severe mental illness (SMI) in Dutch outpatient psychiatric settings. The present study aimed to establish expert consensus on the core components and strategies to optimise practical implementation of a smoking cessation intervention for people treated by Flexible Assertive Community Treatment (FACT) teams in the Netherlands.DesignA modified Delphi method was applied to reach consensus on three core components (behavioural counselling, pharmacological treatment and peer support) of the intervention. The Delphi panel comprised five experts with different professional backgrounds. We proposed a first intervention concept. The panel critically examined the evolving concept in three iterative rounds of 90 min each. Responses were recorded, transcribed verbatim and thematically analysed.ResultsOverall, results yielded that behavioural counselling should focus on preparation for smoking cessation, guidance, relapse prevention and normalisation. Pharmacological treatment consisting of nicotine replacement therapy (NRT), Varenicline or Bupropion, under supervision of a psychiatrist, was recommended. The panel agreed on integrating peer support as a regular part of the intervention, thus fostering emotional and practical support among patients. Treatment of a co-morbid cannabis use disorder needs to be integrated into the intervention if indicated. Regarding implementation, staff's motivation to support smoking cessation was considered essential. For each ambulatory team, two mental health care professionals will have a central role in delivering the intervention.ConclusionsThis study provides insight into expert consensus on the core components of a smoking cessation intervention for people with SMI. The results of this study were used for the development of a comprehensive smoking cessation program.