bluuebunny/crossref_metadata_2025_split huggingface dataset:
Translational findings for odronextamab: From preclinical research to a first‐in‐human study in patients with CD20+ B‐cell malignancies
Authors: Zhu Min , Olson Kara , Kirshner Jessica R. , Khaksar Toroghi Masood , Yan Hong , Haber Lauric , Meagher Craig , Flink Dina M. , Ambati Srikanth R. , Davis John D. , DiCioccio A. Thomas , Smith Eric J. , Retter Marc W. 
Published: January 2022

AbstractOdronextamab is a fully‐human IgG4‐based CD20xCD3 bispecific antibody that binds to CD3 on T cells and CD20 on B cells, triggering T‐cell‐mediated cytotoxicity independent of T‐cell‐receptor recognition. Adequate safety, tolerability, and encouraging durable complete responses have been observed in an ongoing first‐in‐human (FIH) study of odronextamab in patients with relapsed/refractory (R/R) B‐cell non‐Hodgkin lymphoma (B‐NHL; NCT02290951). We retrospectively evaluated the pharmacokinetic, pharmacodynamic, and antitumor characteristics of odronextamab in a series of in vitro/in vivo preclinical experiments, to assess their translational value to inform dose escalation for the FIH study. Half‐maximal effective concentration values from in vitro cytokine release assays (range: 0.05–0.08 mg/L) provided a reasonable estimate of odronextamab concentrations in patients associated with cytokine release at a 0.5 mg dose (maximum serum concentration: 0.081 mg/L) on week 1/day 1, which could therefore be used to determine the week 1 clinical dose. Odronextamab concentrations resulting in 100% inhibition of tumor growth in a Raji xenograft tumor mouse model (1–10 mg/L) were useful to predict efficacious concentrations in patients and inform dose‐escalation strategy. Although predicted human pharmacokinetic parameters derived from monkey data overestimated projected odronextamab exposure, they provided a conservative estimate for FIH starting doses. With step‐up dosing, the highest‐tested weekly odronextamab dose in patients (320 mg) exceeded the 1 mg/kg single dose in monkeys without step‐up dosing. In conclusion, combination of odronextamab in vitro cytokine data, efficacious concentration data from mouse tumor models, and pharmacokinetic evaluations in monkeys has translational value to inform odronextamab FIH study design in patients with R/R B‐NHL.
Evaluation of the knowledge of students concerning sexually transmitted infections in Bavaria/Germany (a cross‐sectional study)
Authors: Rummel Marcel , Clanner‐Engelshofen Benjamin M. , Nellessen Tobias , Zippel Stefan , Schuster Barbara , French Lars E. , Reinholz Markus 
Published: January 2022

SummaryBackground and objectivesDespite numerous information sources and campaigns on sexually transmitted infections (STIs), there has been an increase in STIs in Germany in recent years. The aim was to evaluate the awareness and knowledge level among young students in Bavaria/Germany for STIs with a focus on human papilloma viruses (HPV).MethodsIn a cross‐sectional survey rendered completely and irreversibly anonymous, a total of 4,100 students from Bavaria between the ages of 12 and 17 were interviewed using a multiple choice questionnaire about their knowledge and awareness of STI, on the basis of gender, school education and preventive youth health examinations that had taken place.ResultsA total of 3,834 questionnaires were included in the data analysis. Interestingly, the awareness level for HPV is remarkably lower compared to other STIs. Girls and adolescents who had already taken preventive youth health examinations showed a higher knowledge of STIs on average. Additionally, we could show that adolescents of lower educational levels, such as secondary school students, had the least knowledge.ConclusionsThe cross‐sectional study shows that many young people are still insufficiently informed about STIs. The gaps in information and lack of knowledge underline the necessity of intensive and long‐term educational work.
Global sharing of COVID‐19 vaccines: A duty of justice, not charity
Authors: Jecker Nancy S. 
Published: January 2022

AbstractGlobal scarcity of COVID‐19 vaccines raises ethical questions about their fair allocation between nations. Section I introduces the question and proposes that wealthy nations have a duty of justice to share globally scarce COVID‐19 vaccines. Section II distinguishes justice from charity and argues that beneficiaries of unjust structures incur duties of justice when they are systematically advantaged at others expense. Section III gives a case‐based argument describing three upstream structural injustices that systematically advantaged wealthy countries and disadvantaged poorer countries, contributing to global disparities of COVID‐19 vaccines. Section IV examines more closely the duties of justice owed, including a duty to relinquish holdings, restitute victims, and restore relationships. Section V concludes that wealthy nations have a duty of justice to share COVID‐19 vaccines with poor nations and to restore relationships damaged by injustice. All nations should take steps to transform unjust structures.
Echocardiography for extracorporeal membrane oxygenation
Authors: Hussey Patrick T. , von Mering Gregory , Nanda Navin C. , Ahmed Mustafa I. , Addis Dylan R. 
Published: January 2022

AbstractExtracorporeal membrane oxygenation (ECMO) provides advanced cardiopulmonary life support for patients in cardiac and/or respiratory failure. Echocardiography provides essential diagnostic and anatomic information prior to ECMO initiation, allows for safe and efficient ECMO cannula positioning, guides optimization of flow, provides a modality for rapid troubleshooting and patient evaluation, and facilitates decision‐making for eventual weaning of ECMO support. Currently, guidelines for echocardiographic assessment in this clinical context are lacking. In this review, we provide an overview of echocardiographic considerations for advanced imagers involved in the care of these complex patients. We focus predominately on new cannulas and complex cannulation techniques, including a special focus on double lumen cannulas and a section discussing indirect left ventricular venting. Echocardiography is tremendously valuable in providing optimal care in these challenging clinical situations. It is imperative for imaging physicians to understand the pertinent anatomic considerations, the often complicated physiological and hemodynamic context, and the limitations of the imaging modality.
Systolic and diastolic functional reserve of the subpulmonary and systemic right ventricles as assessed by pharmacologic and exercise stress: A systematic review
Authors: Cheng Sabine , Li Vivian Wing‐Yi , Cheung Yiu‐Fai 
Published: January 2022

AbstractWe performed a systematic review of the literature on the assessment of subpulmonary and systemic right ventricular (RV) functional reserve during pharmacological and exercise stress in congenital heart patients and patients with pulmonary arterial hypertension (PAH). Literature search was conducted using PubMed, EMBASE, and MEDLINE from their inception up to August 2020. Of 913 records identified, 56 studies with a total of 1730 patients were included. Of the 56 studies, 23 assessed subpulmonary RV functional reserve in repaired tetralogy of Fallot patients, 19 assessed systemic RV reserve in patients with transposition of the great arteries (TGA) after atrial switch and those with congenitally corrected TGA, and 14 assessed subpulmonary RV research in patients with PAH. Pharmacological and exercise stress was used, respectively, in 22 and 34 studies. The main findings were (1) impairment of RV systolic and diastolic functional reserve, (2) associations between impaired functional reserve and worse baseline functional parameters, and (3) prognostic implications of RV systolic functional reserve on clinical outcomes in patients with volume and/or pressure‐loaded subpulmonary and systemic right ventricles. Further studies are required to establish the incremental value of incorporating stress studies of RV systolic and diastolic function in the clinical management algorithm of congenital heart patients and patients with PAH.
Three‐dimensional right ventriculo‐arterial coupling as an independent determinant of severe heart failure symptoms in patients with dilated cardiomyopathy
Authors: Vîjîiac Aura , Onciul Sebastian , Deaconu Silvia , Vătășescu Radu , Guzu Claudia , Verinceanu Violeta , Scărlătescu Alina , Zamfir Diana , Petre Ioana , Scafa‐Udriște Alexandru , Dorobanţu Maria 
Published: January 2022

AbstractBackgroundRight ventricular‐pulmonary artery coupling (RVPAC) is a predictor of outcome in pulmonary hypertension. However, the role of this parameter in dilated cardiomyopathy (DCM) remains to be established. The aim of this study was to assess the contribution of RVPAC to the occurrence of severe heart failure (HF) symptoms in patients with DCM using three‐dimensional (3D) echocardiography.MethodsWe prospectively screened 139 outpatients with DCM, 105 of whom were enrolled and underwent 3D echocardiographic assessment. RVPAC was estimated non‐invasively as the 3D right ventricular stroke volume (SV) to end‐systolic volume (ESV) ratio. Severe HF symptoms were defined by New York Heart Association (NYHA) class III or IV. We evaluated differences in RVPAC across NYHA classes and the ability of RVPAC to predict severe symptoms.ResultsMean left ventricular (LV) ejection fraction was 28±7%. Mean RVPAC was 0.77±0.30 and it was significantly more impaired with increasing symptom severity (p = 0.001). RVPAC was the only independent determinant of severe HF symptoms, after adjusting for age, diuretic use, LV systolic function, LV diastolic function, and pulmonary artery systolic pressure (OR 0.035 [95% CI, 0.004–0.312], p = 0.003). By receiver‐operating characteristic analysis, the RVPAC cut‐off value for predicting severely symptomatic status was 0.54 (area under the curve = 0.712, p < 0.001).Conclusion3D echocardiographic SV/ESV ratio is an independent correlate of severe HF symptoms in patients with DCM. 3D RVPAC might prove to be a useful risk stratification tool for these patients, should it be further validated in larger studies.
Phoretic specialization on insect herbivores facilitates mite transportation to host plants
Authors: Bizzarri Laura , Kuprewicz Erin K. , Varma Megana , García‐Robledo Carlos 
Published: January 2022

AbstractPhoresy, the use of another organism for dispersal, is one of the most intriguing commensalistic interactions. The selection of a correct host is fundamental for phoretic organisms to ensure arrival to suitable habitats and to encounter potential mates. This study focuses on a group of phoretic mites in the genus Lasioseius (Acari: Blattisociidae). In La Selva Biological Station, a tropical wet forest in Costa Rica, Lasioseius mites feed on nematodes inside the scrolls formed by the young leaves of their hosts, plants in the order Zingiberales. When leaves expand and unfurl, mites disperse to another rolled leaf by clinging onto ‘rolled‐leaf beetles’, a group of insect herbivores specialized on Zingiberales (genera Cephaloleia and Chelobasis; Coleoptera: Chrysomelidae). In this study, we determined whether Lasioseius mites associated with Cephaloleia belti Baly are specialized on this beetle species as a phoretic host. Mites may also be attracted to Chelobasis perplexa Baly, sharing the same host plant. Another possibility is that Lasioseius mites are opportunistic generalists and attach to rolled‐leaf beetle species (e.g., Cephaloleia dorsalis Baly) that never share host plants with either C. belti or Ch. perplexa. In a laboratory setting, we tested whether mites preferred scents from and/or attached to particular beetle species. Scent attraction experiments showed that Lasioseius mites collected from C. belti were attracted to scents from C. belti and Ch. perplexa, but were not attracted to scents from C. dorsalis. Mites collected from C. belti attached to both C. belti and Ch. perplexa, but never to C. dorsalis. In conclusion, Lasioseius mites are not strict specialists, but are able to detect and attach to beetle species that inhabit their host plant.
Effects of NeemAzal‐T/S on different developmental stages of rose aphid, Macrosiphum rosae
Authors: Bartelsmeier Imke , Kilian Michael , Dicke Marcel 
Published: January 2022

AbstractNatural insecticides often do not provide a strong knock‐down effect and have a lower efficacy than synthetic pesticides. For an effective application of natural insecticides, it is essential to know the product’s mode of action in detail. The efficacy of the commercial neem [Azadirachta indica A. Juss (Meliaceae)] product NeemAzal‐T/S and its influence on stage‐specific mortality, development, and reproduction of rose aphids, Macrosiphum rosae L. (Hemiptera: Aphididae), were determined in greenhouse trials. NeemAzal‐T/S had an efficacy of 40% against M. rosae in standard efficacy trials with initial infestations between 100 and 270 aphids per plant. However, it has a significant impact on the survival of nymphs in the first to third instar as well as on juvenile development. Nymphs treated with NeemAzal‐T/S exhibit a significant delay in molting to the second instar and most of them die before the first molt. Furthermore, reproduction of adult M. rosae females is reduced when aphids are exposed to sub‐lethal concentrations of neem as first instars. Population growth is inhibited or delayed on rose plants treated with NeemAzal‐T/S. The results indicate that applications of NeemAzal‐T/S can be used to control rose aphids in integrated pest management (IPM) systems. Because this insecticide has no rapid knock‐down effect and no effect on adult aphids, combinations with natural enemies of pest insects as well as with other insecticides are possibilities to enhance the efficacy.
Mutation profiling of circulating tumor DNA identifies distinct mutation patterns in non‐Hodgkin lymphoma
Authors: Fu Haiying , Shen Jianzhen , Zhou Huarong , Zhang Feng , Li Hongping , Ma Zhiming , Huang Wanling , Chen Lushan , Chen Yi , Liu Tingbo 
Published: January 2022

AbstractObjectiveCirculating tumor DNA (ctDNA) is emerging as a versatile biomarker for noninvasive genotyping and response monitoring in specific B‐cell lymphomas; however, few studies have been conducted to explore ctDNA‐based mutation profiling across non‐Hodgkin lymphomas (NHLs) and genomic changes after initiation of chemotherapy.MethodsA targeted sequencing of 362 genes was performed to detect the mutation profiles in paired blood and tissue samples from 42 NHL patients. Genomic alterations were explored in 11 diffuse large B‐cell lymphoma (DLBCL) patients using paired blood samples collected pre‐ and post‐R‐CHOP chemotherapy.ResultsThe frequencies of PIM1, MYD88, MYC, ZNF292, JAK, and MAF mutations were higher in aggressive than in indolent B‐cell lymphoma and NK/T subtypes. Tumor mutation burden in blood samples was higher in aggressive than in indolent B‐cell lymphomas and higher in patients who progressed than in those who responded to treatments. Our data also revealed significant enhance of concordance index through integrating mutated genes that were significantly associated with prognosis into International Prognostic Index‐based prognostic model. Moreover, acquisition of mutations such as PCLO_p.L1220Tfs*3 was associated with resistance to R‐CHOP in DLBCL patients.ConclusionsOur findings illustrated distinct mutation patterns across various NHL subtypes and suggested the association of genomic alterations in ctDNA with treatment outcomes.
Ecological validity in exercise neuroscience research: A systematic investigation
Authors: Chang Melissa , Büchel Daniel , Reinecke Kirsten , Lehmann Tim , Baumeister Jochen 
Published: January 2022

AbstractThe contribution of cortical processes to adaptive motor behaviour is of great interest in the field of exercise neuroscience. Next to established criteria of objectivity, reliability and validity, ecological validity refers to the concerns of whether measurements and behaviour in research settings are representative of the real world. Because exercise neuroscience investigations using mobile electroencephalography are oftentimes conducted in laboratory settings under controlled environments, methodological approaches may interfere with the idea of ecological validity. This review utilizes an original ecological validity tool to assess the degree of ecological validity in current exercise neuroscience research. A systematic literature search was conducted to identify articles investigating cortical dynamics during goal‐directed sports movement. To assess ecological validity, five elements (environment, stimulus, response, body and mind) were assessed on a continuum of artificiality–naturality and simplicity–complexity. Forty‐seven studies were included in the present review. Results indicate lowest average ratings for the element of environment. The elements stimulus, body and mind had mediocre ratings, and the element of response had the highest overall ratings. In terms of the type of sport, studies that assessed closed‐skill indoor sports had the highest ratings, whereas closed‐skill outdoor sports had the lowest overall rating. Our findings identify specific elements that are lacking in ecological validity and areas of improvement in current exercise neuroscience literature. Future studies may potentially increase ecological validity by moving from reductionist, artificial environments towards complex, natural environments and incorporating real‐world sport elements such as adaptive responses and competition.
Establishment and evaluation of a quantitative analysis model for potentially toxic metals in wet soil samples by LIBS
Authors: Xu Yuxing , Han Bing , Tan Xin , Jiao Qingbin , Ma Zhenyu , Lv Baolin , Li Yuhang , Li Hui , Zou Yubo , Yang Lin 
Published: January 2022

AbstractFast on‐site detection of potentially toxic metals in soils is crucial for soil remediation and contamination monitoring. The moisture in soils is a challenge for quantitative analysis of potentially toxic metals. Here, we used laser‐induced breakdown spectroscopy (LIBS) and partial least squares regression (PLSR) for fast on‐site quantitative analysis of potentially toxic metals in wet soil samples. The model offered direct measurement of the moisture content in soil samples: the coefficient of determination (R2) value and the root‐mean‐square error of prediction (RMSEP) of predicted moisture content were 0.98% and 1.3%, respectively. The correlation between laser ablation factor and moisture content of the samples was determined by analysing the influence of sample moisture content on laser ablation. Quantitative analysis of wet soil samples based on ablation factor was established with an R2 of 0.97. Potentially toxic elemental Cu and Cr in sample 4# were verified by the quantitative analysis model through weighing and direct measurement. The relative error of concentration was within 10%, and the accuracy was improved by over 80%. The preliminary results show that the quantitative analysis model of potentially toxic metals in wet soil samples based on LIBS technology can detect potentially toxic metals in wet soil samples quickly and accurately on‐site. This has important guiding significance for real‐time and on‐site monitoring of contaminated soils.Highlights
Fast on‐site quantitative analysis of potentially toxic metals in wet soil samples
Quantitative analysis of wet soil samples based on ablation factor was established
The relative error of concentration was within 10%, and the accuracy was improved by over 80%
The model can detect potentially toxic metals in wet soil samples quickly and accurately on‐site
Proposal for an updated seizure classification framework in clinical trials
Authors: Steriade Claude , Sperling Michael R. , DiVentura Bree , Lozano Meryl , Shellhaas Renée A. , Kessler Sudha Kilaru , Dlugos Dennis , French Jacqueline 
Published: January 2022

AbstractThe International League Against Epilepsy (ILAE) seizure classification scheme has been periodically updated to improve its reliability and applicability to clinicians and researchers alike. Here, members of the Epilepsy Study Consortium propose a pragmatic seizure classification, based on the ILAE scheme, designed for use in clinical trials with a focus on outcome measures that have high reliability, broad interpretability across stakeholders, and clinical relevance in the context of the development of novel antiseizure medications. Controversies around the current ILAE classification scheme are discussed in the context of clinical trials, and pragmatic simplifications to the existing scheme are proposed, for intended use by investigators, industry sponsors, and regulatory agencies.
Intracranial electroencephalographic biomarker predicts effective responsive neurostimulation for epilepsy prior to treatment
Authors: Scheid Brittany H. , Bernabei John M. , Khambhati Ankit N. , Mouchtaris Sofia , Jeschke Jay , Bassett Dani S. , Becker Danielle , Davis Kathryn A. , Lucas Timothy , Doyle Werner , Chang Edward F. , Friedman Daniel , Rao Vikram R. , Litt Brian 
Published: January 2022

AbstractObjectiveDespite the overall success of responsive neurostimulation (RNS) therapy for drug‐resistant focal epilepsy, clinical outcomes in individuals vary significantly and are hard to predict. Biomarkers that indicate the clinical efficacy of RNS—ideally before device implantation—are critically needed, but challenges include the intrinsic heterogeneity of the RNS patient population and variability in clinical management across epilepsy centers. The aim of this study is to use a multicenter dataset to evaluate a candidate biomarker from intracranial electroencephalographic (iEEG) recordings that predicts clinical outcome with subsequent RNS therapy.MethodsWe assembled a federated dataset of iEEG recordings, collected prior to RNS implantation, from a retrospective cohort of 30 patients across three major epilepsy centers. Using ictal iEEG recordings, each center independently calculated network synchronizability, a candidate biomarker indicating the susceptibility of epileptic brain networks to RNS therapy.ResultsIctal measures of synchronizability in the high‐γ band (95–105 Hz) significantly distinguish between good and poor RNS responders after at least 3 years of therapy under the current RNS therapy guidelines (area under the curve = .83). Additionally, ictal high‐γ synchronizability is inversely associated with the degree of therapeutic response.SignificanceThis study provides a proof‐of‐concept roadmap for collaborative biomarker evaluation in federated data, where practical considerations impede full data sharing across centers. Our results suggest that network synchronizability can help predict therapeutic response to RNS therapy. With further validation, this biomarker could facilitate patient selection and help avert a costly, invasive intervention in patients who are unlikely to benefit.