bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I dose escalation safety and feasibility study of autologous WT1-sensitized T cells for the treatment of patients with recurrent ovarian cancer
Authors: Kyi Chrisann , Doubrovina Ekaterina , Zhou Qin , Kravetz Sara , Iasonos Alexia , Aghajanian Carol , Sabbatini Paul , Spriggs David , O'Reilly Richard J , O’Cearbhaill Roisin E 
Published: August 2021

BackgroundThis phase I dose escalation trial evaluated the feasibility of production, safety, maximum tolerated dose, and preliminary efficacy of autologous T cells sensitized with peptides encoding Wilms’ tumor protein 1 (WT1) administered alone or following lymphodepleting chemotherapy, in the treatment of patients with recurrent WT1+ ovarian, primary peritoneal, or fallopian tube carcinomas.MethodsA 3+3 dose escalation design was used to determine dose-limiting toxicity (DLT). In cohort I, patients received WT1-sensitized T cells dosed at 5×106/m2 (level I) without cyclophosphamide lymphodepletion. In cohorts II–IV, patients received lymphodepleting chemotherapy (a single intravenous dose of cyclophosphamide 750 mg/m2), 2 days prior to the first intravenous infusion of WT1-sensitized T cells administered at escalating doses (2×107/m2 (level II), 5×107/m2 (level III), and 1×108/m2 (level IV)).ResultsTwelve patients aged 23–72 years, with a median of 7 prior therapies (range 4–14), were treated on the study. No DLT was observed, even at the highest dose level of 1×108/m2 WT1-sensitized T cells tested. Common adverse events reported were grade 1–2 fatigue, fever, nausea, and headache. Median progression-free survival (PFS) was 1.8 months (95% CI, 0.8 to 2.6); 1 year PFS rate 8.3% (95% CI, 0.5 to 31.1). Median overall survival (OS) was 11.0 months (95% CI, 1.1 to 22.6); OS at 1 year was 41.7% (95% CI, 15.2% to 66.5%). Best response was stable disease in one patient (n=1) and progressive disease in the others (n=11). We observed a transient increase in the frequencies of WT1-specific cytotoxic T lymphocyte precursors (CTLp) in the peripheral blood of 9 of the 12 patients following WT1-sensitized T-cell infusion.ConclusionWe demonstrated the safety of administration of WT1-sensitized T cells and the short-term increase in the WT1 CTLp. However, at the low doses evaluated we did not observe therapeutic activity in recurrent ovarian cancer. In this heavily pretreated population, we encountered challenges in generating sufficient numbers of WT1-reactive cytotoxic T cells. Future studies employing WT1-specific T cells generated from lymphocytes are warranted but should be done earlier in the disease course and prior to intensive myelosuppressive therapy.Trial registration numberNCT00562640.One-sentence summaryThe authors describe the first human application of autologous WT1-sensitized T cells in the treatment of patients with recurrent ovarian, primary peritoneal, and fallopian tube carcinomas.
Familial Hypercholesterolemia-Risk-Score: A New Score Predicting Cardiovascular Events and Cardiovascular Mortality in Familial Hypercholesterolemia
Authors: Paquette Martine , Bernard Sophie , Cariou Bertrand , Hegele Robert A. , Genest Jacques , Trinder Mark , Brunham Liam R. , Béliard Sophie , Baass Alexis 
Published: August 2021

Objective:
Familial hypercholesterolemia (FH) is associated with a high risk of premature atherosclerotic cardiovascular disease (ASCVD). However, this risk is highly heterogeneous and current risk prediction algorithms for FH suffer from limitations. The primary objective of this study was to develop a score predicting incident ASCVD events over 10 years in a large multinational FH cohort. The secondary objective was to investigate the prediction of major adverse cardiovascular events and cardiovascular mortality using this score.

Approach and Results:
We prospectively followed 3881 patients with adult heterozygous FH with no prior history of ASCVD (32 361 person-years of follow-up) from 5 registries in Europe and North America. The FH-Risk-Score incorporates 7 clinical variables: sex, age, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, hypertension, smoking, and lipoprotein (a) (Lp(a)) with a Harrell C-index for 10-year ASCVD event of 0.75, which was superior to the SAFEHEART-RE (Spanish Familial Hypercholesterolemia Cohort; 0.69). Subjects with an elevated FH-Risk-Score had decreases in 10-year ASCVD-free survival, 10-year major adverse cardiovascular event-free survival, and 30-year survival for CV mortality compared with the low-risk group, with hazard ratios of 5.52 (3.94–7.73), 4.64 (2.66–8.11), and 10.73 (2.51–45.79), respectively. The FH-Risk-Score showed a similar performance in subjects with and without an FH-causing mutation.

Conclusions:
The FH-Risk-Score is a stronger predictor of future ASCVD than the SAFEHEART-RE and was developed in FH subjects with no prior cardiovascular event. Furthermore, the FH-Risk-Score is the first score to predict CV death and could offer personalized cardiovascular risk assessment and treatment for patients with FH. Future studies are required to validate the FH-Risk-Score in different ethnic groups.
La révolution des disciplines. La rupture entre histoire et géographie en Allemagne
Authors: Hoock Jochen 
Published: August 2021

Resume
Entre fin du XVIIIe et début du XIXe siècle, moment de crise, s’opère dans l’espace germanique une recomposition du champ du savoir et une rupture épistémologique entre deux disciplines jusque-là proches, l’histoire et la géographie. Kant est le premier à formuler leur polarité en la fondant sur la notion de progrès. Les frères Humboldt, l’un historien, l’autre géographe, témoignent de cette autonomisation de l’historiographie et de la géographie modernes. L’affirmation des structures traditionnelles des deux disciplines sera au XXe siècle la réponse aux errements du temps du nazisme et expliquera la forme prise, dans l’Allemagne des années soixante à quatre-vingt-dix, par les débats sur les analyses croisées en termes spatio-temporels.
Time for the Gloves to Come Off?: The Response by the Parliamentary Assembly of the Council of Europe to Rule of Law Backsliding
Authors: Donald Alice , Speck Anne-Katrin 
Published: August 2021

Abstract
The Parliamentary Assembly of the Council of Europe has limited tools to respond to rule of law backsliding by member states. Sanctions have never been used for this purpose, and the Assembly’s monitoring procedure—the most significant tool of scrutiny—presents a mixed picture. This article focuses on four states exhibiting severe rule of law backsliding: Hungary, which has evaded the procedure; Poland, which was placed under monitoring in 2020; Turkey, which in 2017 became the first state to have monitoring reopened; and Azerbaijan, which has been under monitoring since 2001. Through a first-ever analysis of debates, voting patterns, and tactics used in the Assembly, the article elucidates how proponents and opponents of monitoring have framed their arguments in the battleground of ideas about democracy and the rule of law in Europe. It concludes that the Assembly should fundamentally reappraise monitoring—and the possible use of sanctions—to meet the severity of the challenge.
A Closure for the Virtual Origin of Turbulent Plumes
Authors: Tarshish Nathaniel , Romps David M. 
Published: August 2021

Abstract
An isolated source of surface buoyancy, be it a campfire or burning city, gives rise to a turbulent plume. Well above the surface, the plume properties asymptote to the well-known solutions of Morton, Taylor, and Turner (MTT), but a closure is still lacking for the virtual origin. A closure for the virtual origin is sought here in the case of a turbulent plume sustained by a circular source of surface buoyancy in an unstratified and unsheared fluid. In the high-Reynolds-number limit, it is argued that all such plumes asymptote to a single solution. Direct numerical simulation (DNS) of this solution exhibits a virtual origin located a distance below the surface equal to 1.1 times the radius of the buoyancy source. This solution is compared to the previously used assumption that the MTT plume is fully spun up at the surface, and that assumption is found to give buoyancies that are off by an order of magnitude. With regards to the citywide firestorm triggered by the nuclear attack on Hiroshima, it is found that the spun-up-at-surface MTT solution would have trapped radioactive soot within about a hundred meters of the surface, whereas the DNS solution presented here corroborates observations of the plume reaching well into the troposphere.
Understanding the Basin Asymmetry in Surface Response to Sudden Stratospheric Warmings from an Ocean–Atmosphere Coupled Perspective
Authors: Dai Ying , Hitchcock Peter 
Published: August 2021

AbstractThe canonical tropospheric response to a weakening of the stratospheric vortex—an equatorward shift of the eddy-driven jet—is mostly limited to the North Atlantic following sudden stratospheric warmings (SSWs). A coherent change in the Pacific eddy-driven jet is notably absent. Why is this so? Using daily reanalysis data, we show that air–sea interactions over the North Pacific are responsible for the basin-asymmetric response to SSWs. Prior to the onset of some SSWs, their tropospheric precursors produce a dipolar SST pattern in the North Pacific, which then persists as the stratospheric polar vortex breaks down following the onset of the SSW. By reinforcing the lower-tropospheric baroclinicity, the dipolar SST pattern helps sustain the generation of baroclinic eddies, strengthening the near-surface Pacific eddy-driven jet and maintaining its near-climatological-mean state. This prevents the jet from being perturbed by the downward influence of the stratospheric anomalies. As a result, these SSWs exhibit a highly basin-asymmetric surface response with only the Atlantic eddy-driven jet shifted equatorward. For SSWs occurring without the atmospheric precursors in the North Pacific troposphere, the dipolar SST pattern is absent due to the lack of the atmospheric forcing. In the absence of the dipolar SST pattern and the resultant eddy–mean flow feedbacks, these SSWs exhibit a basin-symmetric surface response with both the Atlantic and the Pacific eddy-driven jets shifted equatorward. Our results provide an ocean–atmosphere coupled perspective on stratosphere–troposphere interaction following SSW events and have potential for improving subseasonal to seasonal forecasts for surface weather and climate.
Comparison between dynamic and static sensitivity analysis approaches for impact assessment of different potential evapotranspiration methods on hydrological models performance
Authors: Nonki Rodric Mérimé , Lenouo André , Lennard Christopher J. , Tshimanga Raphael M. , Tchawoua Clément 
Published: August 2021

AbstractPotential Evapotranspiration (PET) plays a crucial role in water management, including irrigation systems design and management. It is an essential input to hydrological models. Direct measurement of PET is difficult, time-consuming and costly, therefore a number of different methods are used to compute this variable. This study compares the two sensitivity analysis approaches generally used for PET impact assessment on hydrological model performance. We conducted the study in the Upper Benue River Basin (UBRB) located in northern Cameroon using two lumped-conceptual rainfall-runoff models and nineteen PET estimation methods. A Monte-Carlo procedure was implemented to calibrate the hydrological models for each PET input while considering similar objective functions. Although there were notable differences between PET estimation methods, the hydrological models performance was satisfactory for each PET input in the calibration and validation periods. The optimized model parameters were significantly affected by the PET-inputs, especially the parameter responsible to transform PET into actual ET. The hydrological models performance was insensitive to the PET input using a dynamic sensitivity approach, while he was significantly affected using a static sensitivity approach. This means that the over-or under-estimation of PET is compensated by the model parameters during the model recalibration. The model performance was insensitive to the rescaling PET input for both dynamic and static sensitivities approaches. These results demonstrate that the effect of PET input to model performance is necessarily dependent on the sensitivity analysis approach used and suggest that the dynamic approach is more effective for hydrological modeling perspectives.
Human bocavirus-1 screening in infants with acute lower respiratory tract infection
Authors: Zhang Xingang , Zheng Jishan , Zhu Lihua , Xu Huiqing 
Published: August 2021

Background Recent studies have reported associations between, human bocavirus (HBoV), and respiratory tract diseases in children. However, there is limited information on the epidemiology of HBoV in infants. This prospective study investigated the prevalence and clinical characteristics of HBoV infection in infants with acute lower respiratory tract infection (ALRTI) in eastern China. Methods Nasopharyngeal aspirates and throat swab samples were collected from infants with ALRTI and age-matched healthy infants between January 2016 and December 2019. HBoV was identified by polymerase chain reaction. Laboratory data and clinical characteristics were analyzed. Results Of 2510 infants, 145 tested positive for HBoV. The highest prevalence of HBoV was detected during the winter. Co-infection was frequently observed during this period of high viral transmission. There were no HBoV-positive infants in the control group. Clinical signs and symptoms included cough, wheezing, fever, nasal discharge, vomiting, diarrhea, hypoxemia, and tachypnea. Co-infections included: Streptococcus pneumoniae, Staphylococcus aureus, Mycoplasma pneumoniae, Chlamydophila pneumoniae, respiratory syncytial virus, and adenovirus. Conclusions HBoV was frequently detected in infants with ALRTI in China. The prevalence of HBoV was highest in winter. Co-infection was common, especially in infants requiring intensive care unit admission. Comprehensive clinical evaluation may facilitate optimal treatment.
Effect of dexmedetomidine on hemodynamics in patients undergoing hysterectomy: a meta-analysis and systematic review
Authors: Li Zhaoqiu , Li Cuiping , Zhang Maoxian 
Published: August 2021

Objective We conducted a meta-analysis and systematic review to evaluate the effects of dexmedetomidine on the hemodynamics of patients undergoing hysterectomy. Methods We searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases for clinical randomized controlled trials (RCTs) that allowed direct or indirect comparisons of hemodynamic indicators. We also searched nine English-language databases up to April 2021 to identify relevant research. The Cochrane risk-of-bias tool for RCTs was applied to assess the methodological quality of the eligible studies. The meta-analysis was conducted using RevMan 5.4 software. Results Nine trials were included in this systematic review. The effect of dexmedetomidine on heart rate during surgery was significantly smaller than that of other sedatives. Intraoperative systolic and diastolic blood pressure and mean arterial pressure were more stable in the dexmedetomidine group compared with the control group. The postoperative modified Observer’s Assessment of Alertness Score was also better in the dexmedetomidine compared with the control group. Conclusions Dexmedetomidine increases hemodynamic stability in patients undergoing hysterectomy, reduces the cardiovascular stress response during surgery, and effectively prevents postoperative adverse reactions, with good safety.
The Climate Crisis, Renewable Energy, and the Changing Landscape of Global Energy Politics
Authors: Albert Michael J. 
Published: August 2021

Abstract This essay reviews three recent books on the changing landscape of global energy politics in the era of climate change. Key questions that the authors investigate include: how will the renewable energy transition reshape the global balance of power? How will political-economic interdependencies and geopolitical alignments shift? Will contemporary petro-states adapt or collapse? And what new patterns of peace and conflict may emerge in a decarbonized world order? The authors provide different perspectives on the likely speed of the energy transition and its geopolitical implications. However, they occlude deeper questions about the depth of the transformations needed to prevent climate catastrophe—particularly in the nature of capitalism and military power—and the potential for more radical perspectives on energy futures. In contrast, I will argue that we should advance a critical research agenda on the global energy transition that accounts for the possibility of more far-reaching transformations in the political-economic, military, and ideological bases of world politics and highlights diverse movements fighting for their realization. These possible transformations include (1) transitions to post-growth political economies; (2) a radical shrinkage of emissions-intensive military–industrial complexes; and (3) decolonizing ideologies of “progress.” If struggles for alternative energy futures beyond the hegemony of economic growth and Western-style modernization are at the forefront of radical politics today, then these struggles deserve greater attention from critical IR scholars.
Return-to-Sport Time and Postoperative Performance in MLB Players Undergoing Wrist Arthroscopy
Authors: Orozco Erin I. , Guloy Andrea E. , Cotton Michael O. , Jack Robert A. , Liberman Shari R. 
Published: August 2021

Background: Wrist injuries are common in sports and can result in prolonged time missed from playing. This study aimed to determine in Major League Baseball-players after arthroscopic wrist surgery the return-to-sport (RTS) rate, postoperative career length, and changes in performance compared with preoperative statistics and matched controls. Methods: Major League Baseball players who underwent arthroscopic wrist surgery from 1990 to 2019 were identified. Demographic and performance data were collected for each player, and matched controls were identified. Comparisons were made via paired samples Student t tests. Results: Twenty-six players (27 surgeries) were identified. The average age of included players was 28.9 ± 2.9 years with an average professional experience of 5.2 ± 3.4 years. Eighty-four percent of players returned to sport, with an average RTS time of 5.0 ± 2.7 months. A statistically significant ( P < .05) decrease was seen in preoperative and postoperative runs scored per season (95.6 ± 91.3 vs 41.0 ± 29.5), batting average (BA) (0.270 ± 0.024 vs 0.240 ± 0.036), and average wins above replacement (WAR) (1.5 ± 1.1 vs 0.8 ± 0.9). Conclusion: Major League Baseball players who underwent arthroscopic wrist surgery had an RTS rate of 84% at a mean time of 5.0 months. There was no significant difference in performance statistics between cases postoperatively and matched controls overall, with some differences in performance found when categorized by position. However, a significant decrease in performance among case players was observed between preoperative and postoperative performance, including runs per season, BA, and WAR.
Prevalence of CYP2C19 and ITGB3 polymorphisms among Bangladeshi patients who underwent percutaneous coronary intervention
Authors: Islam Md Rabiul , Nova Tasnova Tasnim , Momenuzzaman NAM , Rabbi Sikder Nahidul Islam , Jahan Ishrat , Binder Thomas , Islam Mohammad Safiqul , Hasnat Abul , Nahar Zabun 
Published: August 2021

Introduction: Antithrombotic agents are the basic therapeutic option for patients with arterial thrombosis who underwent percutaneous coronary intervention (PCI). In Bangladesh, aspirin and clopidogrel are frequently prescribed as antithrombotics or platelet inhibitors. Studies reported the genetic polymorphisms of CYP2C19*2, CYP2C19*17, and ITGB3 cause an alteration of the pharmacodynamic and pharmacokinetic profile of aspirin and clopidogrel. Therefore, we aimed to assess the prevalence of CYP2C19*2, CYP2C19*17, and ITGB3 polymorphisms among Bangladeshi patients with cardiovascular disease (CVD) who underwent PCI. Methods: Here we assessed a total of 1,000 CVD patients (male 782 and female 218) who underwent PCI and were treated with clopidogrel and/or aspirin. We performed genotyping of patients treated with clopidogrel and aspirin by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) methods. The PCR products of clopidogrel-treated patients were screened with agarose gel electrophoresis and then digested with SmaI and NsiI-HF for CYP2C19*2 and CYP2C19*17, respectively. We genotyped aspirin-treated patients with T-ARMS-PCR for missense rs5918 (PlA1/A1) polymorphism of the ITGB3 gene. Then we ran the digested PCR products on 2% agarose gel electrophoresis to detect the mentioned polymorphisms. Results: Among the clopidogrel-treated patients, we observed 64.1% polymorphism (hetero + mutant) of CYP2C19*2 (loss-of-function allele) and 22.7% (hetero + mutant) of CYP2C19*17 (gain-of-function allele). On the other hand, among the aspirin-treated patients, polymorphisms of ITGB3 were 84.1% homozygous (PlA1/A1), 15.6% heterozygous (PlA1/A2), and 0.3% mutant homozygous. Conclusion: In the present study, we observed a high prevalence of genetic polymorphisms of CYP2C19 and ITGB3 genes. Therefore, we recommend genotyping of CVD patients before prescribing clopidogrel or aspirin to prevent coagulation. Based on the genotyping study, the adjustment of doses or alternative generics might require to avoid therapeutic failure or toxicity in some cases.
Monitor for lactate in perspiration
Authors: Luo Ting-Ting , Sun Zhong-Hai , Li Chu-Xin , Feng Jin-Lian , Xiao Zhao-Xiu , Li Wei-Dong 
Published: August 2021

AbstractSweat is a noninvasive biological fluid on the surface of human skin and has attracted increasing attention as a diagnostic specimen for disease and biomarker detection. Sweat metabolite quantification is possible due to progress in sweat analysis techniques; nevertheless, the role of sweat monitoring in energy metabolism, physiological or pathological state assessment, health status assessment, and the development and outcome of metabolism-related diseases remains unclear. This review provides a comprehensive overview of the literature on human sweat lactate concentration. The first, second, and third sections of this review present an introduction of sweat lactate, methods for the collection and storage of sweat lactate samples, and methods of detection and analysis of sweat lactate, respectively. The fourth section elaborates upon the current state of clinical application of sweat lactate monitoring and its prospects for health surveillance. The last section focuses on the challenges and future directions of this novel technology for detecting lactate in sweat.