Miracle-dz/UniFAR-FTUs huggingface dataset:
The cluster randomized crossover trial: The effects of attrition in the AB/BA design and how to account for it in sample size calculations

Background/Aims: This article studies the effect of attrition in the cluster randomized crossover trial. The focus is on the two-treatment two-period AB/BA design where attrition occurs during the washout period. Attrition may occur at either the subject level or the cluster level. In the latter case, clusters drop out entirely and provide no measurements in the second period. Subject attrition can only occur in the cohort design, where each subject receives both treatments. Cluster attrition can also occur in the cross-sectional design, where different subjects are measured in the two time periods. Furthermore, this article explores two different strategies to account for potential levels of attrition: increasing sample size and replacing those subjects who drop out by others. Methods: The statistical model that takes into account the nesting of subjects within clusters, and the nesting of repeated measurements within subjects is presented. The effect of attrition is evaluated on the basis of the efficiency of the treatment effect estimator. Matrix algebra is used to derive the relation between efficiency, the degree of attrition, cluster size and the intraclass correlations: the within-cluster within-period correlation, the within-cluster between-period correlation and (in the case of a cohort design) the within-subject correlation. The methodology is implemented in two Shiny Apps. Results: Attrition in a cluster randomized crossover trial implies a loss of efficiency. Efficiency decreases with an increase of the attrition rate. The loss of efficiency due to attrition of subjects in a cohort design is largest for small number of subjects per cluster-period, but it may be repaired to a large degree by increasing the number of subjects per cluster-period or by replacing those subjects who drop out by others. Attrition of clusters results in a larger loss of efficiency, but this loss does not depend on the number of subjects per cluster-period. Repairing for this loss requires a large increase in the number of subjects per cluster-period. The methodology of this article is illustrated by an example on the effect of lavender scent on dental patients’ anxiety. Conclusion: This article provides the methodology of exploring the effect of attrition in cluster randomized crossover trials, and to repair for attrition. As such, it helps researchers plan their trial in an appropriate way and avoid underpowered trials. To use the methodology, prior estimates of the degree of attrition and intraclass correlation coefficients are needed. It is advocated that researchers clearly report the estimates of these quantities to help facilitate planning future trials.
The roles of study setting, response bias, and personality in subjective memory complaints of cognitively normal older adults

ABSTRACT Objectives: This study investigated subjective memory complaints in older adults and the roles of setting, response bias, and personality. Design: Cognitively normal older adults from two settings completed questionnaires measuring memory complaints, response bias, and personality. Settings: (A) Neuroimaging study with community-based recruitment and (B) academic memory clinic. Participants: Cognitively normal older adults who (A) volunteer for research (N = 92) or (B) self-referred to a memory clinic (N = 20). Measurements: Neuropsychological evaluation and adjudication of normal cognitive status were done by the neuroimaging study or memory clinic. This study administered self-reports of subjective memory complaints, response bias, five-factor personality, and depressive symptoms. Primary group differences were examined with secondary sensitivity analyses to control for sex, age, and education differences. Results: There was no significant difference in over-reporting response bias between study settings. Under-reporting response bias was higher in volunteers. Cognitive complaints were associated with response bias for two cognitive complaint measures. Neuroticism was positively associated with over-reporting in evaluation-seekers and negatively associated with under-reporting in volunteers. The relationship was reversed for Extraversion. Under-reporting bias was positively correlated with Agreeableness and Conscientiousness in volunteers. Conclusion: Evaluation-seekers do not show bias toward over-reporting symptoms compared to volunteers. Under-reporting response bias may be important to consider when screening for memory impairment in non-help-seeking settings. The Memory Functioning Questionnaire was less sensitive to reporting biases. Over-reporting may be a facet of higher Neuroticism. Findings help elucidate psychological influences on self-perceived cognitive decline and help seeking in aging and may inform different strategies for assessment by setting.
Gastric Cancer in Young Adults: A Different Clinical Entity from Carcinogenesis to Prognosis

Approximately 5.0% of gastric cancer (GC) patients are diagnosed before the age of 40 and are not candidates for screening programs in most countries and regions. The incidence of gastric cancer in young adults (GCYA) has declined over time in most countries except in the United States. Genetic alterations, environmental factors, and lifestyle may predispose some young adults to GC. According to molecular classifications, the cancer of most GCYA patients belongs to the genomically stable or microsatellite stable/epithelial-mesenchymal transition subtype, with the common genetic aberrations being mutations in CDH1. What characterizes GCYA are a higher prevalence in females, more aggressive tumor behaviors, diagnosis at advanced stages, fewer comorbidities and being better treatment candidates, and a similar or better survival outcome when compared with older patients. Considering the greater loss of life-years in younger patients, lowering the incidence of GC and diagnosing at a relatively early stage are the two most effective ways to decrease GC mortality. To achieve these goals, the low awareness of GCYA among general people, policy-makers, clinicians, and researchers should be changed.
The honeysuckle genome provides insight into the molecular mechanism of carotenoid metabolism underlying dynamic flower coloration.

Lonicera japonica is a wide-spread member of the Caprifoliaceae (honeysuckle) family utilized in traditional medical practices. This twining vine honeysuckle is also a much-sought ornamental, in part due to its dynamic flower coloration, which changes from white to gold during development. The molecular mechanism underlying dynamic flower coloration in L. japonica was elucidated by integrating whole genome sequencing, transcriptomic analysis, and biochemical assays. Here, we report a chromosome-level genome assembly of L. japonica, comprising nine pseudo-chromosomes with a total size of 843.2 Mb. We also provide evidence for a whole genome duplication event in the lineage leading to L. japonica, which occurred after its divergence from Dipsacales and Asterales. Moreover, gene expression analysis not only revealed correlated expression of the relevant biosynthetic genes with carotenoid accumulation, but also suggested a role for carotenoid degradation in L. japonica's dynamic flower coloration. The variation of flower color is consistent with not only the observed carotenoid accumulation pattern, but also with the release of volatile apocarotenoids that presumably serve as pollinator attractants. Beyond novel insights into the evolution and dynamics of flower coloration, the high-quality L. japonica genome sequence also provides a foundation for molecular breeding to improve desired characteristics.
Phase 2 study of pembrolizumab in patients with advanced rare cancers

Background Patients with advanced rare cancers have poor prognosis and few treatment options. As immunotherapy is effective across multiple cancer types, we aimed to assess pembrolizumab (programmed cell death 1 (PD-1) inhibitor) in patients with advanced rare cancers. Methods In this open-label, phase 2 trial, patients with advanced rare cancers whose tumors had progressed on standard therapies, if available, within the previous 6 months were enrolled in nine tumor-specific cohorts and a 10th cohort for other rare histologies. Pembrolizumab 200 mg was administered intravenously every 21 days. The primary endpoint was non-progression rate (NPR) at 27 weeks; secondary endpoints were safety and tolerability, objective response rate (ORR), and clinical benefit rate (CBR). Results A total of 127 patients treated between August 15, 2016 and July 27, 2018 were included in this analysis. At the time of data cut-off, the NPR at 27 weeks was 28% (95% CI, 19% to 37%). A confirmed objective response (OR) was seen in 15 of 110 (14%) evaluable patients (complete response in one and partial response in 14). CBR, defined as the percentage of patients with an OR or stable disease ≥4 months, was 38% (n=42). Treatment was ongoing in 11 of 15 patients with OR at last follow-up. In the cohort with squamous cell carcinoma (SCC) of the skin, the NPR at 27 weeks was 36%, ORR 31%, and CBR 38%. In patients with adrenocortical carcinoma (ACC), NPR at 27 weeks was 31%, ORR 15%, and CBR 54%. In the patients with carcinoma of unknown primary (CUP), NPR at 27 weeks was 33%, ORR 23%, and CBR 54%. In the paraganglioma–pheochromocytoma cohort, NPR at 27 weeks was 43%, ORR 0%, and CBR 75%. Treatment-related adverse events (TRAEs) occurred in 66 of 127 (52%) patients, and 12 (9%) had grade ≥3 TRAEs. The most common TRAEs were fatigue (n=25) and rash (n=17). There were six deaths, all of which were unrelated to the study drug. Conclusions The favorable toxicity profile and antitumor activity seen in patients with SCC of skin, ACC, CUP, and paraganglioma–pheochromocytoma supports further evaluation of pembrolizumab in this patient population. Trial registration number NCT02721732
Impact of temperature on the extrinsic incubation period of Zika virus in Aedes aegypti

Since Zika virus (ZIKV) emerged as a global human health threat, numerous studies have pointed to Aedes aegypti as the primary vector due to its high competence and propensity to feed on humans. The majority of vector competence studies have been conducted between 26–28°C, but arboviral extrinsic incubation periods (EIPs), and therefore transmission efficiency, are known to be affected strongly by temperature. To better understand the relationship between ZIKV EIPs and temperature, we evaluated the effect of adult mosquito exposure temperature on ZIKV infection, dissemination, and transmission in Ae. aegypti at four temperatures: 18°C, 21°C, 26°C, and 30°C. Mosquitoes were exposed to viremic mice infected with a 2015 Puerto Rican ZIKV strain, and engorged mosquitoes were sorted into the four temperatures with 80% RH and constant access to 10% sucrose. ZIKV infection, dissemination, and transmission rates were assessed via RT-qPCR from individual mosquito bodies, legs and wings, and saliva, respectively, at three to five time points per temperature from three to 31 days, based on expectations from other flavivirus EIPs. The median time from ZIKV ingestion to transmission (median EIP, EIP50) at each temperature was estimated by fitting a generalized linear mixed model for each temperature. EIP50 ranged from 5.1 days at 30°C to 24.2 days at 21°C. At 26°C, EIP50 was 9.6 days. At 18°C, only 15% transmitted by day 31 so EIP50 could not be estimated. This is among the first studies to characterize the effects of temperature on ZIKV EIP in Ae. aegypti, and the first to do so based on feeding of mosquitoes on a live, viremic host. This information is critical for modeling ZIKV transmission dynamics to understand geographic and seasonal limits of ZIKV risk; it is especially relevant for determining risk in subtropical regions with established Ae. aegypti populations and relatively high rates of return travel from the tropics (e.g. California or Florida), as these regions typically experience cooler temperature ranges than tropical regions.
Disease progression across the spectrum of idiopathic pulmonary fibrosis: A multicentre study

In clinical practice, a working diagnosis of IPF may be performed to provide effective antifibrotic treatment to patients who cannot undergo SLB. In this study, we compared the disease course across IPF diagnostic categories in a real‐life clinical setting to clarify the appropriateness of a working diagnosis of IPF and treatment initiation in these patients.
The Role of Biofilms Developed under Different Anthropogenic Pressure on Recruitment of Macro-Invertebrates

Microbial biofilms can be key mediators for settlement of macrofoulers. The present study examines the coupled effects of microbial biofilms and local environmental conditions on the composition, structure and functioning of macrofouling assemblages. Settlement of invertebrates over a gradient of human-impacted sites was investigated on local biofilms and on biofilms developed in marine protected areas (MPAs). Special attention was given to the presence of non-indigenous species (NIS), a global problem that can cause important impacts on local assemblages. In general, the formation of macrofouling assemblages was influenced by the identity of the biofilm. However, these relationships varied across levels of anthropogenic pressure, possibly influenced by environmental conditions and the propagule pressure locally available. While the NIS Watersipora subatra seemed to be inhibited by the biofilm developed in the MPA, Diplosoma cf. listerianum seemed to be attracted by biofilm developed in the MPA only under mid anthropogenic pressure. The obtained information is critical for marine environmental management, urgently needed for the establishment of prevention and control mechanisms to minimize the settlement of NIS and mitigate their threats.
Trivalent Glycoprotein Subunit Vaccine Prevents Neonatal Herpes Simplex Virus Mortality and Morbidity

Herpes simplex virus is among the most serious infections of newborns. Current antiviral therapies can prevent mortality if infection is recognized early and treated promptly. Most children who survive nHSV develop lifelong neurological and behavioral deficits, despite aggressive antiviral treatment. We propose that maternal immunization could provide protection against HSV for both mother and baby. To this end, we used a trivalent glycoprotein vaccine candidate to demonstrate that offspring are protected from nHSV following maternal immunization. Significantly, this approach protected offspring from long-term behavioral morbidity. Our results emphasize the importance of providing protective immunity to neonates during this window of vulnerability. ABSTRACT Herpes simplex virus (HSV) can cause severe infection in neonates leading to mortality and lifelong morbidity. Prophylactic approaches, such as maternal immunization, could prevent neonatal HSV (nHSV) infection by providing protective immunity and preventing perinatal transmission. We previously showed that maternal immunization with a replication-defective HSV vaccine candidate, dl5-29, leads to transfer of virus-specific antibodies into the neonatal circulation and protects against nHSV neurological sequela and mortality (C. D. Patel, I. M. Backes, S. A. Taylor, Y. Jiang, et al., Sci Transl Med, 11:eaau6039, 2019, https://doi.org/10.1126/scitranslmed.aau6039). In this study, we evaluated the efficacy of maternal immunization with an experimental trivalent (gC2, gD2, and gE2) subunit vaccine to protect against nHSV. Using a murine model of nHSV, we demonstrated that maternal immunization with the trivalent vaccine protected offspring against nHSV-disseminated disease and mortality. In addition, offspring of immunized dams were substantially protected from behavioral pathology following HSV infection. This study supports the idea that maternal immunization is a viable strategy for the prevention of neonatal infections. IMPORTANCE Herpes simplex virus is among the most serious infections of newborns. Current antiviral therapies can prevent mortality if infection is recognized early and treated promptly. Most children who survive nHSV develop lifelong neurological and behavioral deficits, despite aggressive antiviral treatment. We propose that maternal immunization could provide protection against HSV for both mother and baby. To this end, we used a trivalent glycoprotein vaccine candidate to demonstrate that offspring are protected from nHSV following maternal immunization. Significantly, this approach protected offspring from long-term behavioral morbidity. Our results emphasize the importance of providing protective immunity to neonates during this window of vulnerability.
Blood Eosinophil Counts in Clinical Trials for Chronic Obstructive Pulmonary Disease

Precision medicine is an approach that combines individual clinical characteristics with additional biological information to distinguish between patients with similar diagnoses, with the aim of predicting disease course and treatment response. Biomarkers have an important role in the practical implementation of precision medicine and enrichment of clinical trial populations. For patients with chronic obstructive pulmonary disease, higher blood eosinophil counts, in combination with clinical characteristics, are associated with increased response to corticosteroids and targeted therapies. A single blood eosinophil count cutoff value is not appropriate for identification of potential treatment response, because often a continuous relationship exists between blood eosinophil counts and treatment response. Response also varies with clinical characteristics such as exacerbation risk and current smoking status. Future incorporation of blood eosinophil counts into clinical trials could potentially reduce drug development costs and trial failures. Including blood eosinophil counts as a biomarker in clinical trials will also provide further opportunities to evaluate aspects of eosinophil testing and standardization of methodology and clinical utility. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Cold‐stored leukoreduced CPDA‐1 whole blood: in vitro quality and hemostatic properties

Some jurisdictions require leukoreduction of cellular blood components. The only whole blood collection set with a platelet‐saving filter uses citrate‐phosphate‐dextrose (CPD) as storage solution. Substituting CPD with citrate‐phosphate‐dextrose‐adenine (CPDA‐1) increases shelf life from 21 to 35 days. This would simplify prehospital and rural resupply and reduce wastage. We investigated in vitro quality and hemostatic properties of CPDA‐1 whole blood leukoreduced with a platelet‐saving filter.
Myo-inositol oxygenese activity in second trimester of pregnancy: altered myoinositol catabolism in gestational diabetes mellitus

Abstract Objective We aimed to determine myo-inositol oxygenase (MIOX) activity in gestational diabetes mellitus (GDM). Material and Methods The insulin, HbA1c, and MIOX levels of 80 pregnant women were analysed after 75 g OGTT. Group I included patients with no risk factor for GDM, Group II: patients with high risk for GDM, and Group III: GDM patients. Results Fasting plasma glucose and Homeostatic Model Assessment for Insulin Resistance index were significantly higher in GDM cases (Group 3). Regarding the MIOX levels, significantly higher levels were recorded at 0-h in Group 3 compared to Groups 1 and 2. Significant alteration in MIOX activity was found between 0- and 2-h in Group 3 compared to Groups 1 and 2 (p < .029). Conclusions MIOX levels were higher in GDM cases so, it may be have a role in myo-inositol catabolism.
The Antihypertensive, Antimicrobial and Anticancer peptides from Arthrospira with therapeutic potential: A minireview.

The interest in biological peptides from Arthrospira sp. (syn Spirulina) is increasing due to its GRAS status, the high concentration of proteins and the history of its use as a supplement and nutraceutical agent. Arthrospira peptides can be generated by controlled hydrolysis of the proteins, using proteases, followed by fractionation. The peptides obtained have a range of therapeutic effects. Amongst these bioactive peptides, three classes are of major importance: the antihypertensive (AHP), antimicrobial (AMP) and anticancer (ACP) peptides. AHPs have the ability to work as inhibitors of ACE, the angiotensin-converting enzyme, and help to control several diseases such as hypertension, obesity, and cardiovascular issues. AMPs play a crucial role in the immune response, inhibiting the development of pathogens such as bacteria, fungi, viruses and others. ACPs can aid in tumor control by induction of apoptosis, necrosis, or inhibition of the angiogenesis. Thus, bioactive peptides are of great significance to the pharmaceutical industry. However, they can show secondary effects. This paper reviews the inhibition mechanism of antimicrobial, hypertensive and anticancer peptides from Arthrospira sp. , and the possible structures of the peptides according to the type of activity and its intensity. In addition, this paper describes the purification methods, absorption mechanisms, and reviews databases for designing peptides.
Characteristics and Functions of the Rumen Microbial Community of Cattle-Yak at Different Ages

A cattle-yak, which is a hybrid between a yak (Bos grunniens) and cattle (Bos taurus), is an important livestock animal, but basic questions regarding its physiology and environmental adaptation remain unanswered. To address this issue, the present study examined the species composition and functional characteristics of rumen microorganisms in the cattle-yak of different ages (2 and 3 years old) by metagenomic analysis. We found that rumen microbial community composition was similar at the two ages. Firmicutes, Fibrobacteres, Euryarchaeota, Bacteroidetes, and Proteobacteria were the predominant phyla, with Firmicutes accounting for the highest percentage of bacteria in 2-year-old (48%) and 3-year-old (46%) animals. Bacterial species involved in lignocellulose degradation were detected in the rumen of adult cattle-yaks including Ruminococcus flavefaciens, Ruminococcus albus, Fibrobacter succinogenes, and Prevotella ruminicola, with F. succinogenes being the most abundant. A total of 145,489 genes were annotated according to the Carbohydrate-active Enzyme database, which identified glycoside hydrolases as the most highly represented enzyme family. Further functional annotation revealed specific microflora and genes in the adult rumen that are potentially related to plateau adaptability. These results could explain the heterosis of the cattle-yak and provide insight into mechanisms of physiologic adaptation in plateau animals.
Permanent left bundle branch pacing: What is the mechanism of divergent responses during programmed stimulation?

An 18-year-old girl with congenital complete AV block and epicardial VVI pacemaker implanted at the age of 4 months was admitted for endocardial DDD pacemaker implantation due to the development of pacing induced cardiomyopathy (exercise intolerance with left ventricular ejection fraction of 44%). Considering narrow QRS of the ventricular escape rhythm, permanent His bundle pacing was chosen as a potentially optimal pacing mode to prevent progression / reverse cardiomyopathy. This article is protected by copyright. All rights reserved.