Miracle-dz/UniFAR-FTUs huggingface dataset:
Skipping the line: bringing MET exon 14 skipping mutations to the forefront of targeted therapy

with advanced age and stage-dependent met genomic amplification and c-met overexpression. Clin The reported frequencies of MET exon 14 skipping mutations in lung adenocarcinomas consistently range in the 3–4% range ( Table 1 ) and a uniquely aggressive subtype of lung cancer, so-called sarcomatoid lung cancer has been reported to harbor a much higher, up to 25–35%, frequency of these mutations (9-13).
Can Treadmill Slip-Perturbation Training Reduce Longer-Term Fall Risk Upon Overground Slip Exposure?

The purpose was to examine and compare the longer-term generalization between 2 different practice dosages for a single-session treadmill slip-perturbation training when reexposed to an overground slip 6 months later. A total of 45 older adults were conveniently assigned to either 24 or 40 slip-like treadmill perturbation trials or a third control group. Overground slips were given immediately after initial training, and at 6 months after initial training in order to examine immediate and longer-term effects. The performance (center of mass stability and vertical limb support) and fall percentage from the laboratory-induced overground slips (at initial posttraining and at 6 mo) were measured and compared between groups. Both treadmill slip-perturbation groups showed immediate generalization at the initial posttraining test and longer-term generalization at the 6-month retest. The higher-practice-dosage group performed significantly better than the control group (P < .05), with no difference between the lower-practice-dosage and the control groups at the 6-month retest (P > .05). A single session of treadmill slip-perturbation training showed a positive effect for reducing older adults' fall risk for laboratory-induced overground slips. A higher-practice dosage of treadmill slip perturbations could be more beneficial for further reducing fall risk.
Baculovirus Expression and Functional Analysis of Vpa2 Proteins from Bacillus thuringiensis

The mode of action underlying the insecticidal activity of the Bacillus thuringiensis (Bt) binary pesticidal protein Vpb/Vpa (formerly Vip1/Vip2) is uncertain. In this study, three recombinant baculoviruses were constructed using Bac-to-Bac technology to express Vpa2Ac1 and two novel Vpa2-like genes, Vpa2-like1 and Vpa2-like2, under the baculovirus p10 promoter in transfected Sf9 cells. Pairwise amino acid analyses revealed a higher percentage of identity and a lower number of gaps between Vpa2Ac1 and Vpa2-like2 than to Vpa2-like1. Moreover, Vpa2-like1 lacked the conserved Ser-Thr-Ser motif, involved in NAD binding, and the (F/Y)xx(Q/E)xE consensus sequence, characteristic of the ARTT toxin family involved in actin polymerization. Vpa2Ac1, Vpa2-like1 and Vpa2-like2 transcripts and proteins were detected in Sf9 culture cells, but the signals of Vpa2Ac1 and Vpa2-like2 were weak and decreased over time. Sf9 cells infected by a recombinant bacmid expressing Vpa2-like1 showed typical circular morphology and produced viral occlusion bodies (OBs) at the same level as the control virus. However, expression of Vpa2Ac1 and Vpa2-like2 induced cell polarization, similar to that produced by the microfilament-destabilizing agent cytochalasin D and OBs were not produced. The presence of filament disrupting agents, such as nicotinamide and nocodazole, during transfection prevented cell polarization and OB production was observed. We conclude that Vpa2Ac1 and Vpa2-like2 proteins likely possess ADP-ribosyltransferase activity that modulated actin polarization, whereas Vpa2-like1 is not a typical Vpa2 protein. Vpa2-like2 has now been designated Vpa2Ca1 (accession number AAO86513) by the Bacillus thuringiensis delta-endotoxin nomenclature committee.
Nothing Wrong with the Analysis of Clades in Comparative Evolutionary Studies: A Reply to Poe et al

Abstract In a recent paper, Poe et al. assert that scientists should abandon clade-based approaches, particularly those using named taxonomic ranks. Poe et al. attempt to demonstrate that clade selection can have effects on the results of evolutionary analyses but unfortunately fall short of making any robust conclusions. Here, we demonstrate that the assertions made by Poe et al. have two important flaws: (i) an erroneous view of modern phylogenetic comparative methods; and (ii) a lack of statistical rigor in their analyses. We repeat Poe et al.’s analysis but using appropriate phylogenetic comparative approaches. We demonstrate that results remain consistent regardless of the clade definition. We go on to discuss the value of taxonomic groupings and how they can provide meaningful units of comparison in evolutionary study. Unlike the disheartening suggestion to abandon the use of clades, scientists can instead continue to use phylogenetic “ corrections” that are already the standard for most comparative evolutionary analyses. [Comparative methods; evolution; phylogeny; taxonomy. ]
Impact, theory of change, and the horizons of scientific practice

Demands for research to generate impact, along with proliferating institutional regimes for evaluating impact, are a ubiquitous aspect of contemporary scientific practice. Based on participant observation at an agro-environmental research institute in southwest China, this article explores three iterations of a tool for planning and evaluating impactful science called ‘theory of change’ (TOC). Despite their ostensible common grounding in TOC, I show how an impact scientist’s framework, a donor’s monitoring and evaluation regime, and a communication consultant’s branding strategy each suggest very different normative structures for scientific practice. These structures entail: particular horizons towards which scientific research is to be practiced, precise points in time at which the future effects of research are to be anticipated, and specific assumptions about how scientists’ agency should play out across time. Taking the peculiar sensibilities of TOC as a comparative framework, I illuminate IFF scientists’ implicit imaginations of how contemporary science does and should generate effects in the world.
Stigma and COVID‐19 crisis: A wake‐up call

To the Editor Public health emergencies in times of epidemics and the effects of contagion mitigation strategies such as emergency lockdown may cause intense fear and anxiety particularly among the at‐risk populations. Correia has also emphasized that health systems globally have diverted attention and resources toward the fight of COVID‐19. This has significantly hampered the management of other serious health issues such as mental and chronic conditions particularly in low‐ and middle‐income countries where resources for health are often limited. This may certainly have both immediate and long‐term deleterious public health impacts during and even beyond the pandemic. More importantly, the emergence of COVID‐19 and the concomitant contagions have resulted in prejudices, community rejection and intense stigma against the infected and affected persons. The allied neuropsychological impacts on the direct medical issues of the pandemic such disruptions, anxiety, stress, stigma and xenophobia may also cause mayhem in the society and social lives. Pervasive social stigma and discriminatory behaviors are being demonstrated toward the frontline health and social workers and the vulnerable, at‐risk population including older adults. Emerging evidence from many parts of sub‐Saharan Africa (SSA) shows that many people who have recovered and those recovering from COVID‐19 as well as their families and close relevant others have been thrust into extreme stigmatization. Diverse media reports document instances where COVID‐19 suspected persons have been ejected from their rented apartments and turned away from shops especially after completing mandatory quarantine. Such behaviors and actions may likely cause not only hostility and social disruptions but also interfere vehemently with the countermeasures against COVID‐19. Lessons from previous outbreaks such as the MERS‐COV, HIV and Ebola epidemic suggest that stigma tends to persist during and postepidemic. We offer viewpoints on how COVID‐19‐related stigma affects the mental health of the infected and affected people and propose measures to address this social canker especially in SSA.
A recurrent circuit implements normalization, simulating the dynamics of V1 activity

Significance A family of recurrent circuit models is proposed to explain the dynamics of neural activity in primary visual cortex (V1). Each of the models in this family exhibits steady-state output responses that are already known to fit a wide range of experimental data from diverse neural systems. These models can recapitulate the complex dynamics of V1 activity, including oscillations (so-called gamma oscillations, ∼30 to 80 Hz). This theoretical framework may also be used to explain key aspects of working memory and motor control. Consequently, the same circuit architecture is applicable to a variety of neural systems, and V1 can be used as a model system for understanding the neural computations in many brain areas. The normalization model has been applied to explain neural activity in diverse neural systems including primary visual cortex (V1). The model’s defining characteristic is that the response of each neuron is divided by a factor that includes a weighted sum of activity of a pool of neurons. Despite the success of the normalization model, there are three unresolved issues. 1) Experimental evidence supports the hypothesis that normalization in V1 operates via recurrent amplification, i.e., amplifying weak inputs more than strong inputs. It is unknown how normalization arises from recurrent amplification. 2) Experiments have demonstrated that normalization is weighted such that each weight specifies how one neuron contributes to another’s normalization pool. It is unknown how weighted normalization arises from a recurrent circuit. 3) Neural activity in V1 exhibits complex dynamics, including gamma oscillations, linked to normalization. It is unknown how these dynamics emerge from normalization. Here, a family of recurrent circuit models is reported, each of which comprises coupled neural integrators to implement normalization via recurrent amplification with arbitrary normalization weights, some of which can recapitulate key experimental observations of the dynamics of neural activity in V1.
Next‐generation assessment of human epidermal growth factor receptor 2 gene (ERBB2) amplification status in invasive breast carcinoma: a focus on Group 4 by use of the 2018 American Society of Clinical Oncology/College of American Pathologists HER2 testing guideline

The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) updated the testing guideline in 2018 to address issues arising from uncommon human epidermal growth factor receptor 2 (HER2) fluorescence in‐situ hybridisation (FISH) results according to the 2013 guideline. Next‐generation sequencing (NGS) may be used to better classify patients. The aim of this study was to assess the ERBB2 amplification status of invasive breast carcinoma with equivocal HER2 immunohistochemistry (IHC) results by using NGS, focusing on Group 4 (HER2/CEP17 ratio of <2.0; average HER2 signals/cell of ≥4.0 and <6.0).
Fracture load and microcrack comparison of crowns manufactured from tooth‐shaped and traditional blocks

This study intended to analyze microcracks and fractographic markings on the surface of all ceramic crowns after milling and compare the fracture loads. 90 crowns were manufactured from two feldspathic (Priticrown‐Pr and Vita Mark II‐Vi) and a lithium disilicate (EmaxCAD‐Em) blocks (n = 30). Two groups (n = 15) were prepared for each ceramic. In the first group, crowns were analyzed twice via the fluorescent penetrant method for microcrack detection, after the manufacturing process and thermal cycles. The load to fracture test was applied at a crosshead speed of 0.5 mm/min until catastrophic failure. Second group crowns were directly cemented onto the Co‐Cr dies following the manufacturing process and loaded to fracture. Fractographic markings were analyzed through scanning electron microscope. Spearman correlation analysis, Kruskal–Wallis H test, Mann–Whitney U test, and Wilcoxon Signed Rank test were applied (α = .05). Fracture loads of Em crowns were higher than other groups (p < .05), with and without the aging procedure. Except for second group Pr (r = −.532), no significant relationship was found between microcrack numbers and fracture loads (p > .05). Thermal cycling did not affect microcrack numbers and fracture loads (p > .05). Tooth‐shaped multilayered Pr blocks did not provide an advantage in terms of microcrack and fracture loads.
Impact of an interprofessional training ward on interprofessional competencies – a quantitative longitudinal study

ABSTRACT Complex learning strategies, like interprofessional training wards in which students work autonomously in interprofessional collaboration, can support the development of interprofessional competencies in terms of knowledge, abilities and attitudes. To assess the short-term and long-term effects of a three to five weeks placement on such an interprofessional training ward on nursing and medical undergraduates, a study with pre-post-follow-up design was conducted from April 2017 until February 2019. Outcome measures were the University of the West of England Interprofessional Questionnaire (UWE-IP), the Interprofessional Socialization and Valuing Scale (ISVS), and the Assessment of Interprofessional Team Collaboration Scale (AITCS) measuring interprofessional competencies, including teamwork, communication, interprofessional learning, collaboration, and socialization. 60 medical and 63 nursing undergraduates of the first 16 interprofessional student teams that were placed on the Heidelberg interprofessional training ward (HIPSTA) between April 2017 and November 2018 were included in the study. Data was analyzed using the linear mixed model analysis for longitudinal comparisons of scores before, directly after and three months after the placement on the interprofessional training ward. Statistically significant positive short-term effects in interprofessional competencies were found in all three questionnaires, with effect sizes up to d = 1.05. Statistically significant positive long-term effects with effect sizes up to d = 0.60 were found in the ISVS and the AITCS concerning socialization and collaboration. These results indicate that interprofessional education in a clinical setting positively influences the participants’ perception of interprofessional socialization and teamwork. This may possibly lead to improved interprofessional collaboration in their further career. Strategies to yield a sustainable improvement of attitudes toward interprofessional interaction are still needed.
Newborn micronutrient status biomarkers in a cluster-randomized trial of antenatal multiple micronutrient compared with iron folic acid supplementation in rural Bangladesh

ABSTRACT Background Daily antenatal multiple micronutrient (MM) compared with iron folic acid (IFA) supplementation from early pregnancy improved birth outcomes and maternal micronutrient status in rural Bangladesh, but effects on newborn status are unknown. Objective We examined cord blood micronutrient biomarkers in relation to antenatal MM and IFA supplementation and maternal gestational micronutrient status in rural Bangladeshi newborns. Design In a double-blinded, cluster-randomized trial of antenatal IFA or MM (with the same IFA content), we analyzed cord blood plasma from 333 singleton births, and corresponding maternal plasma at 32.5 ± 2.6 wk of gestation, for ferritin (iron stores), folate, cobalamin (vitamin B-12), retinol (vitamin A), 25-hydroxyvitamin D [25(OH)D, vitamin D status], α-tocopherol (vitamin E), zinc, thyroglobulin, and free thyroxine (iodine status). Intervention effects and associations were determined using linear regression, exploring maternal status as a mediator of intervention effects on cord biomarkers. Results The MM intervention increased cord ferritin (mean: +12.4%; 95% CI: 1.3, 24.6%), 25(OH)D (mean: +14.7%; 95% CI: 4.8, 25.6%), and zinc (mean: +5.8%; 95% CI: 1.0, 10.8%). Cord folate (mean: +26.8%; 95% CI: 19.6, 34.5%), cobalamin (mean: +31.3%; 95% CI: 24.6, 38.3%), 25(OH)D (mean: +26.7%; 95% CI: 23.2, 30.3%), α-tocopherol (mean: +8.7%; 95% CI: 3.6, 13.7%), zinc (mean: +2.3%; 95% CI: 0.5, 4.2%), thyroglobulin (mean: +20.1%; 95% CI: 9.0, 32.2%) and thyroxine (mean: +1.5%; 95% CI: 0.0, 3.0%) increased per 1-SD increment in maternal status (all P < 0.05); ferritin and retinol changed by +2.0%; 95% CI: −8.9, 14.3%; P = 0.72; and +3.5%; 95% CI: −0.4, 7.3%; P = 0.07, respectively. Ferritin, folate, cobalamin, zinc, and thyroglobulin averaged 1.57–6.75 times higher and retinol, α-tocopherol, and 25(OH)D 0.30–0.84 times lower in cord than maternal plasma, suggesting preferential maternal–fetal transfer of iron, folate, cobalamin, and zinc; limited transfer of fat-soluble vitamins; and high fetal iodine demand. Conclusions Antenatal MM supplementation increased newborn ferritin, 25(OH)D, and zinc, while maternal and newborn folate, vitamins B-12, D, and E, zinc, and iodine biomarkers were positively related. Despite limited effects of MM, better maternal micronutrient status was associated with improved micronutrient status of Bangladeshi newborns. This trial was registered at clinicaltrials.gov as NCT00860470.
Fibrin hydrogels promote scar formation and prevent therapeutic angiogenesis in the heart

Therapeutic angiogenesis is the delivery of factors to promote vascular growth and holds promise for the treatment of ischemic heart conditions. Recombinant protein delivery to the myocardium by factor‐decorated fibrin matrices is an attractive approach, thanks to the ability to precisely control both dose and duration of the treatment, the use of a clinically approved material like fibrin, and the avoidance of genetic modification. Here, we investigated the feasibility of inducing therapeutic angiogenesis in the rat myocardium by a state‐of‐the‐art fibrin‐based delivery platform that we previously optimized. Engineered versions of murine vascular endothelial growth factor A (VEGF164) and platelet‐derived growth factor BB (PDGF‐BB) were fused with an octapeptide substrate of the transglutaminase coagulation factor fXIIIa (TG) to allow their covalent cross‐linking into fibrin hydrogels and release by enzymatic cleavage. Hydrogels containing either 100 μg/mL TG‐VEGF alone or in combination with 10 μg/mL TG‐PDGF‐BB or no factor were injected into rat myocardium. Surprisingly, vascular density was severely reduced in all conditions, both in and around the injection site, where large fibrotic scars were formed. Scar formation was not due to the presence of growth factors, adaptive immunity to human proteins, damage from injection, nor to mechanical trauma from the hydrogel stiffness or volume. Rather scar was induced directly by fibrin and persisted despite hydrogel degradation within 1 week. These results caution against the suitability of fibrin‐based platforms for myocardial growth factor delivery, despite their efficacy in other tissues, like skeletal muscle. The underlying molecular mechanisms must be further investigated in order to identify rational targets to prevent this serious side effect.
Authentic Empathy and the Role of Victim Service Providers in (De)stigmatizing Male Sexual Victimization

Male victims of rape and sexual violence (SV) constitute a highly stigmatized group who doubly suffer the trauma of SV and hegemonic notions of real masculinity that punishes weakness and vulnerability in men. This double exposure produces a stigmatizing identity (i.e., male victim stigma) that is embedded in grand narratives about male SV. However, helping professionals have been implicated in this (de)stigmatizing process. Few studies describe the role victim service providers (VSPs) play as (de)stigmatizing agents. This study is among the first to explore VSP narratives on their stigma awareness and stigma management practices. Story-focused interview methods elicited responses from 11 VSPs (nine females and two males, age: 29–65 years) across the United States representing diverse victim-serving professions. Interviews were face-to-face or by phone, lasting between 45 and 90 minutes. Interviews were transcribed verbatim and analyzed using power-sensitive Foucauldian discourse analysis (or FDA, suitable for analyzing language and meanings linked to power dynamics). Our analysis was guided by a meaning-forming social constructionist approach. With some narrative convergence and disconvergence, three strings of narratives with supporting excerpts were identified, namely (a) stigma awareness shaped by discursive and material forces, (b) labeling as a (de)stigmatizing tool, and (c) connecting through authentic empathy (AE). The concept of AE is recommended as a possible model of care and stigma management approach in therapeutic spaces. We define AE as an aptitude to credibly provide nonjudgmental, stigma-free care, based on personal histories with trauma, membership in a stigmatized group, or an earned involvement with members of the same group. Findings bear implications for stigma-informed practices and future research to address the unique unmet needs of stigmatized male victims.
Human Challenge Studies Are Unlikely to Accelerate Coronavirus Vaccine Licensure Due to Ethical and Practical Issues

Kingdom, or Scandinavia) or by patient reporting. Vaccine safety information can be collected by established systems like the Vaccine Safety Datalink in the United States [7], prescription event monitoring programs (eg, the Drug Surveillance Research Unit in the United Kingdom [8]), or by direct patient safety reporting on websites, including those accessible with smartphones [9], which can be specifically designed for vaccine trials. Among the advantages of using the LSRT design are that it allows central randomization of large numbers of volunteers within a short time and rapid collection of the relevant outcomes at a low cost compared to the conventional phase 3 trials with many follow-up visits and extensive monitoring. Adaptive design features (eg, modification of the eligibility criteria considering the accruing safety information) are feasible as well. Given the wide entry criteria, the results provide external validity for large parts of the population compared to any challenge trial, which would need to focus on participants with extremely low risks for developing serious COVID-19. As there will be very many people who would like to participate in such a vaccination trial, the sample sizes needed should be achieved within a very short time. When the LSRT double-blind design is used, the validity of the results is assured and it does not generate the serious ethical issues inherent in challenge trials. Regarding the Salk vaccine, large randomized trials with sample sizes of more than 70 000 were done in the early 1950s [10] and such LSRTs should be feasible in 2020. Thus, the sponsors of vaccine trials and the drug regulatory agencies should start the preparatory work now to be ready once an investigational vaccine is ready to be administered on a large scale.