bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of single‐dose and double‐dose ivermectin early treatment in preventing progression to hospitalization in mild COVID‐19: A multi‐arm, parallel‐group randomized, double‐blind, placebo‐controlled trial
Authors: Mirahmadizadeh Alireza , Semati Ali , Heiran Alireza , Ebrahimi Mostafa , Hemmati Abdolrasool , Karimi Mohammadreza , Basir Souzan , Zare Marjan , Charlys da Costa Antonio , Zeinali Mohammad , Sargolzaee Maryam , Eilami Owrang 
Published: June 2022

AbstractBackground and objectiveIvermectin is a known anti‐parasitic agent that has been investigated as an antiviral agent against coronavirus disease 2019 (COVID‐19). This study aimed to evaluate the efficacy of ivermectin in mild COVID‐19 patients.MethodsIn this multi‐arm randomized clinical trial conducted between 9 April 2021 and 20 May 2021, a total of 393 patients with reverse transcription‐PCR‐confirmed COVID‐19 infection and mild symptoms were enrolled. Subjects were randomized in a 1:1:1 ratio to receive single‐dose ivermectin (12 mg), double‐dose ivermectin (24 mg) or placebo. The primary outcome was need for hospitalization.ResultsThere was no significant difference in the proportion of subjects who required hospitalization between the placebo and single‐dose ivermectin groups (absolute difference in the proportions: −2.3 [95% CI = −8.5, 4.1]) and between the placebo and double‐dose ivermectin groups (absolute difference in the proportions: −3.9 [95% CI = −9.8, 2.2]). The odds of differences in mean change in severity score between single‐dose ivermectin and placebo groups (ORdifference = 1.005 [95% CI: 0.972, 1.040]; p = 0.762) and double‐dose ivermectin and placebo groups (ORdifference = 1.010 [95% CI: 0.974, 1.046]; p = 0.598) were not statistically significant. None of the six adverse events (including mild dermatitis, tachycardia and hypertension) were serious and required extra action.ConclusionSingle‐dose and double‐dose ivermectin early treatment were not superior to the placebo in preventing progression to hospitalization and improving clinical course in mild COVID‐19.
Katie Erikson's caring theories. Part 2. The theory of caritative caring ethics and the theory of evidence
Authors: Bergbom Ingegerd , Nyström Lisbet , Nåden Dagfinn 
Published: June 2022

AbstractIn this article, Katie Eriksson's theory of caritative caring ethics and the theory of evidence, are described. Both theories are anchored in caritas, that is love, mercy and compassion. The theory of caritative caring ethics was first described by Eriksson in 1995, where seven assumptions or basic categories were elaborated. These were: the human being's dignity, the care relationship, invitation, responsibility, virtue, obligation or duty, and good and evil. Eriksson's theoretical contribution is that she makes a distinction between caring and nursing ethics, between inner and external ethics, and between natural and clinical ethics. Concerning the theory of evidence, Eriksson claims that a multidimensional scientific view of evidence in caring that focuses on the patient's world is necessary and vital. To see, realise, know, attest and revise constitute the ontological definitions of the concepts of evidence and evident. The theories are united by the core concepts of testimony and witnessing the human being's suffering. Eriksson points out that it is in the ethical acts that deeds are formed, based on ethos. The anchorage in an ethos means to have firm value‐loaded judgements of an inner motive. Moreover, the anchorage in ethos presupposes a personal and natural ethic. The good deeds are realised in the relationship between the patient and the carer, but the caring ethics is not a professional or external ethics. Caring ethics is an ontological inner ethics meaning fellowship and the right to exist, but it is the patient's world and reality that decides the foundation and starting point for caritative caring ethics in clinical practice. The ultimate purpose and goal of caring are to guarantee the patient's dignity and absolute value as a human being.
Sympathetic vasomotor outflow during low‐intensity leg cycling in healthy older males
Authors: Katayama Keisho , Saito Mitsuru , Ishida Koji , Shimizu Kaori , Shiozawa Kana , Mizuno Sahiro , Ogoh Shigehiko 
Published: June 2022

New Findings
What is the central question of this study?
Sympathetic vasomotor outflow is reduced during low‐intensity dynamic leg exercise in younger individuals: does ageing influence the sympathoinhibitory effect during low‐intensity leg cycling?

What is the main finding and its importance?
Muscle sympathetic nerve activity during low‐intensity cycling decreased in older males, as seen in young males. It is possible that cardiopulmonary baroreflex‐mediated inhibition of sympathetic vasomotor outflow during dynamic leg exercise is preserved in healthy older males.

AbstractMuscle sympathetic nerve activity (MSNA) is reduced during low‐intensity dynamic leg exercise in young males. It is suggested that this inhibition is mediated by loading of the cardiopulmonary baroreceptors. The purpose of this study was to clarify the impact of age on MSNA during dynamic leg exercise. Nine younger males (YM, mean ± SD, 20 ± 1 years) and nine older males (OM, 72 ± 3 years) completed the study. The subjects performed two 4‐min cycling exercises at 10% of their heart rate reserve using a cycle ergometer in a semirecumbent position (MSNA and estimated central venous pressure (eCVP) trials). MSNA was recorded via microneurography of the left radial nerve. The CVP was estimated based on peripheral venous pressure, which was monitored using a cannula in the right large antecubital vein. The magnitude of the increase in mean arterial blood pressure during leg cycling was larger in OM (+9.3 ± 5.5 mmHg) compared with YM (+2.8 ± 4.7 mmHg). MSNA burst frequency was decreased during cycling in both YM (–8.1 ± 3.8 bursts/min) and OM (–10.6 ± 3.3 bursts/min), but no significant difference was found between the two groups. The eCVP increased during exercise in both groups, and there was no difference in the changes in eCVP between YM (+1.1 ± 0.4 mmHg) and OM (+1.2 ± 0.7 mmHg). These data indicate that inhibition of sympathetic vasomotor outflow during low‐intensity cycling appears in OM as seen in YM. It is possible that the muscle pump‐induced loading of the cardiopulmonary baroreflex is preserved during cycling in healthy older males.
Model-Based Acetabular Cup Orientation Optimization Based on Minimizing the Risk of Edge-Loading and Implant Impingement Following Total Hip Arthroplasty
Authors: Danaei Behzad , McPhee John 
Published: June 2022

Abstract
In this paper, a computationally efficient model-based method for determining patient-specific optimal acetabular cup alignment for total hip arthroplasty (THA) is presented. The proposed algorithm minimizes the risk of implant impingement and edge-loading, which are reported as the major causes of hip dislocation following THA. First, by using motion capture data recorded from the patient performing different daily activities, the hip contact force and the relative orientation of the femur and pelvis are calculated by a musculoskeletal model. Then, by defining two quantitative indices, i.e., angular impingement distance and angular edge-loading distance (AED), the risk of impingement and edge-loading are assessed for a wide range of cup alignments. Finally, three optimization criteria are introduced to estimate the optimal cup alignment with a tradeoff between the risk of impingement and edge loading. The results show that patient-specific characteristics such as pelvic tilt could significantly change the optimal cup alignment, especially the value of cup anteversion. Therefore, in some cases, the well-known Lewinnek safe zone may not be optimal, or even safe. Unlike other dynamic model-based methods, in this work, the need for force plate measurements is eliminated by estimating the ground reaction forces and moments, which makes this method more practical and cost-efficient. Furthermore, the low computational complexity due to analytical formulas makes this method suitable for both pre-operative and intra-operative planning.
Improve Syntax Correctness and Breadth of Design Space Exploration in Functional Analysis
Authors: She Jinjuan , Belanger Elise , Bartels Caroline , Reeling Hunter 
Published: June 2022

Abstract
Functional analysis aims to decompose the main functions of a product, which can be large and complex, into more manageable subfunctions. Recently, interest in explicitly considering users during functional modeling has grown to enhance analysis completeness, but how this addresses some commonly reported challenges for novice engineers is not clear. This research proposes and assesses a simple way to streamline user considerations in functional analysis as potential mitigation for some challenges (i.e., difficulty in identifying functions to explore design space and expressing the functions with expected syntax and solution neutrality) that novice designers frequently mention at the early design stage. Analysis of the results indicates that embedding requirements into a user workflow supports novice designers generate significantly more functions with correct syntax than starting with requirements only. In addition, the exploration space is prominently broader, especially at the higher levels measured by the geometry of the generated hierarchical models. These results suggest that strategically incorporating user considerations, even in a simple way, positively addresses the common challenges. This initial exploration and assessment could serve as an inspiration for future research on more efficient ways to streamline the functional decomposition process and, in turn, better support subsequent systematic conceptual design.
Self-Paced Cycling at the Highest Sustainable Intensity With Blood Flow Restriction Reduces External but Not Internal Training Loads
Authors: Smith Nathan D.W. , Peiffer Jeremiah J. , Girard Olivier , Scott Brendan R. 
Published: June 2022

Purpose: This study compared training loads and internal:external load ratios from an aerobic interval session at the highest perceptually sustainable intensity with and without blood flow restriction (BFR). Methods: On separate days, 14 endurance cyclists/triathletes completed four 4-minute self-paced aerobic cycling intervals at their highest sustainable intensity, with and without BFR (60% of arterial occlusion pressure). Internal training load was quantified using 3 training impulses (TRIMP; Banister, Lucia, and Edwards) and sessional ratings of perceived exertion. External load was assessed using total work done (TWD). Training load ratios between all internal loads were calculated relative to TWD. Results: Lucia TRIMP was lower for the BFR compared with non-BFR session (49 [9] vs 53 [8] arbitrary units [au], P = .020, dz = −0.71). No between-conditions differences were observed for Banister TRIMP (P = .068), Edwards TRIMP (P = .072), and training load in sessional ratings of perceived exertion (P = .134). The TWD was lower for the BFR compared with non-BFR session (223 [52] vs 271 [58] kJ, P < .001, dz = −1.27). Ratios were greater for the BFR session compared with non-BFR for Lucia TRIMP:TWD (0.229 [0.056] vs 0.206 [0.056] au, P < .001, dz = 1.21), Edwards TRIMP:TWD (0.396 [0.105] vs 0.370 [0.088] au, P = .031, dz = 0.66), and training load in sessional ratings of perceived exertion:TWD (1.000 [0.266] vs 0.890 [0.275] au, P = .044, dz = 0.60), but not Banister TRIMP:TWD (P = .306). Conclusions: Practitioners should consider both internal and external loads when monitoring BFR exercise to ensure the demands are appropriately captured. These BFR-induced changes were reflected by the Lucia TRIMP:TWD and Edwards TRIMP:TWD ratio, which could be used to monitor aerobic BFR training loads. The Lucia TRIMP:TWD ratio likely represents BFR-induced changes more appropriately compared with ratios involving either Edwards or Banister TRIMP.
Clustered cardiovascular disease risk among children aged 8–13 years from lower socioeconomic schools in Gqeberha, South Africa
Authors: Dolley Danielle , Walter Cheryl , du Randt Rosa , Pühse Uwe , Bosma Jacob , Aerts Ann , Adams Larissa , Arnaiz Patricia , Degen Jan , Gall Stefanie , Joubert Nandi , Müller Ivan , Nienaber Madeleine , Nqweniso Felicitas , Seelig Harald , Steinmann Peter , Utzinger Jürg , Gerber Markus 
Published: June 2022

ObjectivesTo determine the prevalence of individual cardiovascular disease (CVD) risk factors and clustered CVD risk among children attending schools in periurban areas of Gqeberha and to investigate the independent association between clustered CVD risk, moderate to vigorous physical activity (MVPA) and cardiorespiratory fitness (CRF).MethodsBaseline data were collected in a cross-sectional analysis of 975 children aged 8–13 years. We measured the height, weight, waist circumference, blood pressure, fasting glucose, full lipid panel, 20 m shuttle run performance and accelerometry. The prevalence of individual risk factors was determined, and a clustered risk score (CRS) was constructed using principal component analysis. Children with an elevated CRS of 1 SD above the average CRS were considered ‘at-risk’.ResultsWe found 424 children (43.3%) having at least one elevated CVD risk factor: 27.7% elevated triglycerides, 20.7% depressed high-density lipoprotein cholesterol and 15.9% elevated total cholesterol. An elevated clustered risk was identified in 17% (n=104) of the sample; girls exhibited a significantly higher CRS >1 SD than boys (p=0.036). The estimated odds of an elevated clustered risk are doubled every 2 mL/kg/min decrease in VO2max (95% CI 1.66 to 3.12) or every 49 min reduction in MVPA (95% CI 27 to 224).ConclusionA relatively high prevalence of elevated individual and clustered CVD risk was identified. Our results have also confirmed the independent inverse association of the clustered CVD risk with physical activity and CRF. These indicate that increased levels of CRF or MVPA may aid in the prevention and reduction of elevated clustered CVD risk.
Naldemedine-laxative combination: retrospective inpatient study
Authors: Takemura Miho , Niki Kazuyuki , Miyaguchi Sho , Ueda Mikiko 
Published: June 2022

ObjectivesThe initiation of peripherally acting μ-opioid receptor antagonists (PAMORAs) should be considered 2 weeks after conventional laxatives have failed to achieve an adequate response, and affected patients should be evaluated every 2 weeks thereafter. However, this guidance is difficult to implement in acute care hospitals. This study aimed to examine how naldemedine (PAMORA) should be introduced in combination with other laxatives in the acute care setting.MethodsThis retrospective study evaluated 93 inpatients who received at least four doses of naldemedine. We investigated changes in the average daily defecation counts during the first 7 days after compared with before naldemedine administration and the incidence of diarrhoea.ResultsDaily defecation counts during the first 7 days after compared with before naldemedine administration were greater in both the naldemedine, magnesium oxide (MgO) and another laxative group, and in the naldemedine and another laxative other than MgO group than in the naldemedine only group. The incidence rates of diarrhoea were significantly higher in the naldemedine, MgO, and another laxative group, and in the naldemedine and another laxative other than MgO group than in the naldemedine only group.ConclusionsThe introduction of naldemedine alone or in combination with MgO should be considered.
The Central Role of mTORC1 in Amino Acid Sensing
Authors: Yue Shusheng , Li Guanya , He Shanping , Li Tingting 
Published: June 2022

Abstract
The mTOR is a master regulator of cell growth that controls cell homeostasis in response to nutrients, growth factors, and other environmental cues. Recent studies have emphasized the importance of lysosomes as a hub for nutrient sensing, especially amino acid sensing by mTORC1. This review highlights recent advances in understanding the amino acid–mTORC1 signaling axis and the role of mTORC1 in cancer.
Genomic Profiling of Bronchoalveolar Lavage Fluid in Lung Cancer
Authors: Nair Viswam S. , Hui Angela Bik-Yu , Chabon Jacob J. , Esfahani Mohammad S. , Stehr Henning , Nabet Barzin Y. , Zhou Li , Chaudhuri Aadel A. , Benson Jalen , Ayers Kelsey , Bedi Harmeet , Ramsey Meghan , Van Wert Ryan , Antic Sanja , Lui Natalie , Backhus Leah , Berry Mark , Sung Arthur W. , Massion Pierre P. , Shrager Joseph B. , Alizadeh Ash A. , Diehn Maximilian 
Published: June 2022

Abstract

Genomic profiling of bronchoalveolar lavage (BAL) samples may be useful for tumor profiling and diagnosis in the clinic. Here, we compared tumor-derived mutations detected in BAL samples from subjects with non–small cell lung cancer (NSCLC) to those detected in matched plasma samples. Cancer Personalized Profiling by Deep Sequencing (CAPP-Seq) was used to genotype DNA purified from BAL, plasma, and tumor samples from patients with NSCLC. The characteristics of cell-free DNA (cfDNA) isolated from BAL fluid were first characterized to optimize the technical approach. Somatic mutations identified in tumor were then compared with those identified in BAL and plasma, and the potential of BAL cfDNA analysis to distinguish lung cancer patients from risk-matched controls was explored. In total, 200 biofluid and tumor samples from 38 cases and 21 controls undergoing BAL for lung cancer evaluation were profiled. More tumor variants were identified in BAL cfDNA than plasma cfDNA in all stages (P &lt; 0.001) and in stage I to II disease only. Four of 21 controls harbored low levels of cancer-associated driver mutations in BAL cfDNA [mean variant allele frequency (VAF) = 0.5%], suggesting the presence of somatic mutations in nonmalignant airway cells. Finally, using a Random Forest model with leave-one-out cross-validation, an exploratory BAL genomic classifier identified lung cancer with 69% sensitivity and 100% specificity in this cohort and detected more cancers than BAL cytology. Detecting tumor-derived mutations by targeted sequencing of BAL cfDNA is technically feasible and appears to be more sensitive than plasma profiling. Further studies are required to define optimal diagnostic applications and clinical utility.

Significance:
Hybrid-capture, targeted deep sequencing of lung cancer mutational burden in cell-free BAL fluid identifies more tumor-derived mutations with increased allele frequencies compared with plasma cell-free DNA.
See related commentary by Rolfo et al., p. 2826
Comparison of Computed Tomography Perfusion and Multiphase Computed Tomography Angiogram in Predicting Clinical Outcomes in Endovascular Thrombectomy
Authors: Tan Zefeng , Parsons Mark , Bivard Andrew , Sharma Gagan , Mitchell Peter , Dowling Richard , Bush Steven , Churilov Leonid , Xu Anding , Yan Bernard 
Published: June 2022

Background:
In patients with acute stroke who undergo endovascular thrombectomy, the relative prognostic power of computed tomography perfusion (CTP) parameters compared with multiphase CT angiogram (mCTA) is unknown. We aimed to compare the predictive accuracy of mCTA and CTP parameters on clinical outcomes.

Methods:
We included patients with acute ischemic stroke who had anterior circulation large vessel occlusion within 24 hours of onset in Melbourne Brain Centre at the Royal Melbourne Hospital. All patients underwent CTP for endovascular thrombectomy, and the mCTA collateral score was determined using CTP-reconstructed mCTA images. The primary outcome was 90-day functional outcomes defined by modified Rankin Scale. Multivariable logistic regression models analyzed associations between mCTA and CTP parameters and 90-day functional outcomes. The ability to discriminate 90 days-functional outcomes was compared between mCTA collateral score and CTP parameters using receiver operating curve analysis and C statistics.

Results:

One hundred and twenty patients were included. The median age was 69 years (interquartile range, 60–79), the median baseline National Institutes of Health Stroke Scale score was 14 (interquartile range, 9–19). The baseline ischemic core volume, defined by CTP-based relative cerebral blood flow <30%, was associated with excellent functional outcome (modified Rankin Scale score 0–1; odds ratio, 0.942 [−0.897 to −0.989];
P
=0.015) and poor functional outcome (modified Rankin Scale score 5–6; odds ratio, 1.032 [1.007–1.056];
P
=0.010) at 90 days in the analysis of multivariable regression. There was no significant association between the mCTA score and excellent functional outcome (
P
=0.58) or poor functional outcome (
P
=0.155). The relative cerebral blood flow <30%-based regression model best fit the data for the 90-day poor functional outcome (C statistic, 0.834).

Conclusions:
The CTP-based ischemic core volume may provide better discrimination for 90-day functional outcomes for patients with acute stroke undergoing endovascular thrombectomy than the mCTA collateral score.
The global neuronal workspace as a broadcasting network
Authors: Wajnerman Paz Abel 
Published: June 2022

Abstract
A new strategy for moving forward in the characterization of the global neuronal workspace (GNW) is proposed. According to Dehaene, Changeux, and colleagues (Dehaene, 2014, pp. 304, 312; Dehaene & Changeux, 2004, 2005), broadcasting is the main function of the GNW. However, the dynamic network properties described by recent graph theoretic GNW models are consistent with many large-scale communication processes that are different from broadcasting. We propose to apply a different graph theoretic approach, originally developed for optimizing information dissemination in communication networks, which can be used to identify the pattern of frequency and phase-specific directed functional connections that the GNW would exhibit only if it were a broadcasting network.
Crucifixion Practices
Authors: van Wingerden Ruben 
Published: June 2022

Abstract
Ancient crucifixion has been the subject of some major studies in the last twenty years. However, they remain silent on how the patibulum was attached to the vertical post or stipes, either with or without an individual. This issue is addressed in this article. The author describes modern approaches to this issue and suggests that there is evidence that nails were used in attaching the patibulum to the crux/stipes. Moreover, the author suggests that the crux/stipes was not imagined to be always already erected before the patibulum was attached, contrary to what is usually related. The Gospel of Peter implies that both beams were attached to each other on the ground before being raised up, and this practice is attested with similar capital punishments in Antiquity as well.