Miracle-dz/UniFAR-FTUs huggingface dataset:
Environmental Contact and Self-contact Patterns of Healthcare Workers: Implications for Infection Prevention and Control

Abstract Background Respiratory viruses on fomites can be transferred to sites susceptible to infection via contact by hands or other fomites. Methods Care for hospitalized patients with viral respiratory infections was observed in the patient room for 3-hour periods at an acute care academic medical center for over a 2 year period. One trained observer recorded the healthcare activities performed, contacts with fomites, and self-contacts made by healthcare workers (HCWs), while another observer recorded fomite contacts of patients during the encounter using predefined checklists. Results The surface contacted by HCWs during the majority of visits was the patient (90%). Environmental surfaces contacted by HCWs frequently during healthcare activities included the tray table (48%), bed surface (41%), bed rail (41%), computer station (37%), and intravenous pole (32%). HCWs touched their own torso and mask in 32% and 29% of the visits, respectively. HCWs’ self-contacts differed significantly among HCW job roles, with providers and respiratory therapists contacting themselves significantly more times than nurses and nurse technicians (P < .05). When HCWs performed only 1 care activity, there were significant differences in the number of patient contacts and self-contacts that HCWs made during performance of multiple care activities (P < .05). Conclusions HCWs regularly contact environmental surfaces, patients, and themselves while providing care to patients with infectious diseases, varying among care activities and HCW job roles. These contacts may facilitate the transmission of infection to HCWs and susceptible patients.
A network of phosphatidylinositol 4,5-bisphosphate binding sites regulates gating of the Ca2+-activated Cl− channel ANO1 (TMEM16A)

Significance Membrane proteins dwell in a sea of phospholipids that not only structurally stabilize the proteins by providing a hydrophobic environment for their transmembrane segments but also dynamically regulate protein function. While many cation channels are known to be regulated by phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], relatively little is known about anion channel regulation by phosphoinositides. Using a combination of patch-clamp electrophysiology and atomistic molecular-dynamics simulations, we have identified several PI(4,5)P2 binding sites in ANO1 (TMEM16A), a Cl− channel that performs myriad physiological functions from epithelial fluid secretion to regulation of electrical excitability. These binding sites form a band at the cytosolic interface of the membrane that we propose constitute a network to dynamically regulate this highly allosteric protein. ANO1 (TMEM16A) is a Ca2+-activated Cl− channel that regulates diverse cellular functions including fluid secretion, neuronal excitability, and smooth muscle contraction. ANO1 is activated by elevation of cytosolic Ca2+ and modulated by phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Here, we describe a closely concerted experimental and computational study, including electrophysiology, mutagenesis, functional assays, and extended sampling of lipid–protein interactions with molecular dynamics (MD) to characterize PI(4,5)P2 binding modes and sites on ANO1. ANO1 currents in excised inside-out patches activated by 270 nM Ca2+ at +100 mV are increased by exogenous PI(4,5)P2 with an EC50 = 1.24 µM. The effect of PI(4,5)P2 is dependent on membrane voltage and Ca2+ and is explained by a stabilization of the ANO1 Ca2+-bound open state. Unbiased atomistic MD simulations with 1.4 mol% PI(4,5)P2 in a phosphatidylcholine bilayer identified 8 binding sites with significant probability of binding PI(4,5)P2. Three of these sites captured 85% of all ANO1–PI(4,5)P2 interactions. Mutagenesis of basic amino acids near the membrane–cytosol interface found 3 regions of ANO1 critical for PI(4,5)P2 regulation that correspond to the same 3 sites identified by MD. PI(4,5)P2 is stabilized by hydrogen bonding between amino acid side chains and phosphate/hydroxyl groups on PI(4,5)P2. Binding of PI(4,5)P2 alters the position of the cytoplasmic extension of TM6, which plays a crucial role in ANO1 channel gating, and increases the accessibility of the inner vestibule to Cl− ions. We propose a model consisting of a network of 3 PI(4,5)P2 binding sites at the cytoplasmic face of the membrane allosterically regulating ANO1 channel gating.
Functional Specialization in the Attention Network.

Spatial attention is comprised of neural mechanisms that boost sensory processing at a behaviorally relevant location while filtering out competing information. The present review examines functional specialization in the network of brain regions that directs such preferential processing. This attention network includes both cortical (e.g., frontal and parietal cortices) and subcortical structures (e.g., the superior colliculus and the pulvinar nucleus of the thalamus). Here, we piece together existing evidence that these various nodes of the attention network have dissociable functional roles by synthesizing results from electrophysiology and neuroimaging studies. We describe functional specialization across several dimensions (e.g., at different processing stages and within different behavioral contexts), while focusing on spatial attention as a dynamic process that unfolds over time. Functional contributions from each node of the attention network can change on a moment-to-moment timescale, providing the necessary cognitive flexibility for sampling from highly dynamic environments. Expected final online publication date for the Annual Review of Psychology, Volume 71 is January 4, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Fucoxanthin-Rich Brown Algae Extract Improves Male Reproductive Function on Streptozotocin-Nicotinamide-Induced Diabetic Rat Model

Hypogonadism and oxidative stress are occurring commonly in men with diabetes and associated male infertility. This study aimed to investigate the capability of anti-oxidative and anti-inflammatory properties of fucoxanthin as well as to evaluate its protective effects on male reproduction in diabetic rats. The RAW 264.7 macrophage cells were used to evaluate the anti-oxidative and anti-inflammatory activity. Thirty male Sprague-Dawley rats were induced by streptozotocin-nicotinamide for a diabetes model and fed either with three different doses of fucoxanthin (13, 26, and 65 mg/kg) or rosiglitazone (0.571 mg/kg) for four weeks. The fucoxanthin significantly inhibited nitric oxide production and reduced reactive oxygen species level in lipopolysaccharide-induced RAW 264.7 cells. In the animal study, fucoxanthin administration improved insulin resistance, restored sperm motility, decreased abnormal sperm number, and inhibited lipid peroxidation. Moreover, it restored GPR54 and SOCS-3 mRNA expression in the hypothalamus and recovered luteinizing hormone level, as well as the testosterone level. In conclusion, fucoxanthin not only possessed antioxidant and anti-inflammatory properties but also decreased the diabetes signs and symptoms as well as improved spermatogenesis and male reproductive function.
Bleomycin use in the treatment of Hodgkin lymphoma (HL): toxicity and outcomes in the modern era

Abstract One-in-five Hodgkin Lymphoma (HL) patients treated with bleomycin develop bleomycin pulmonary toxicity (BPT). Given bleomycin-omission data with negative interim-PET, we assessed changes in BPT statistics. We retrospectively evaluated 126 ABVD-treated HL patients for overall survival (OS), progression-free survival (PFS), BPT factors, and management. Forty-seven patients developed BPT with 17% BPT-mortality. In univariable analysis, OS was negatively impacted by BPT (HR = 3.6, 95%CI = 1.2–10.6), but not bleomycin-omission (HR = 1.3, 95%CI = 0.5–3.7). In multivariable analysis, BPT was not associated with OS (HR = 3.0, 95%CI = 0.9–9.9). BPT patients were older (46 y vs 33 years) and received less bleomycin (107 vs 215 units) compared to non-BPT patients. BPT was managed primarily with bleomycin-omission. “Recent Era” patients had lower BPT rates (28% vs 48%), mortality (10% vs 21%), and bleomycin doses (7 vs 12 doses), yet higher bleomycin-omission in the absence of the BPT (59% vs 8%) compared to “Early Era”. Our data suggest BPT continually impacts OS in ABVD-treated HL patients, however management is changing.
Multiple proteins arising from a single gene: The role of the Spa33 variants in Shigella T3SS regulation

Shigella invasion and dissemination in intestinal epithelial cells relies on a type 3 secretion system (T3SS), which mediates translocation of virulence proteins into host cells. T3SSs are composed of three major parts: an extracellular needle, a basal body, and a cytoplasmic complex. Three categories of proteins are hierarchically secreted: (a) the needle components, (b) the translocator proteins which form a pore (translocon) inside the host cell membrane and (c) the effectors interfering with the host cell signaling pathways. In the absence of host cell contact, the T3SS is maintained in an “off” state by the presence of a tip complex. Secretion is activated by host cell contact which allows the release of a gatekeeper protein called MxiC. In this work, we have investigated the role of Spa33, a component of the cytoplasmic complex, in the regulation of secretion. The spa33 gene encodes a 33‐kDa protein and a smaller fragment of 12 kDa (Spa33C) which are both essential components of the cytoplasmic complex. We have shown that the spa33 gene gives rise to 5 fragments of various sizes. Among them, three are necessary for T3SS. Interestingly, we have shown that Spa33 is implicated in the regulation of secretion. Indeed, the mutation of a single residue in Spa33 induces an effector mutant phenotype, in which MxiC is sequestered. Moreover, we have shown a direct interaction between Spa33 and MxiC.
Induced degradation of protein kinases by bifunctional small molecules: a next-generation strategy

ABSTRACT Introduction: Protein kinases are a major target for small-molecule drug development. However, relatively few compounds are free of off-target toxicity and reach the clinic. Because the 500-plus kinases share conserved ATP-binding clefts, the site targeted by competitive inhibitors, generation of specific therapeutics remains a nearly intractable challenge. Areas covered: Inducing degradation, instead of inhibition by occupancy-driven drugs, is an emerging strategy that offers the long-sought specificity, as well as mechanistic benefits. Currently approved inhibitors require steady-state binding and leave proteins intact for interactions in multi-protein complexes. After a general background about induced protein degradation, perspectives on protein kinases are provided. Expert opinion: Induced degradation by state-of-the-art compounds (proteolysis-targeting chimeras, PROTACs) has been shown for protein kinases, albeit in early pre-clinical stages. Further work is required to expand the number of enzymes that could be exploited to direct proteins for degradation by ubiquitylation. In addition, despite the simple modularity of the chimeras, generation of hits will require empirical approaches due to the role of protein–protein interactions and distribution of tagging sites. However, given the advantages of degradation, drug discovery efforts targeting protein kinases should increasingly shift toward generation and screening of inducers of degradation and away from occupancy-based inhibitors of old.
Histologic Findings of Advanced Fibrosis and Cirrhosis in Patients With Nonalcoholic Fatty Liver Disease Who Have Normal Aminotransferase Levels.

OBJECTIVES Patients with nonalcoholic fatty liver disease (NAFLD) and normal aminotransferase levels may have advanced liver histology. We conducted a study to characterize the prevalence of and factors associated with advanced liver histology in patients with histologically characterized NAFLD and normal aminotransferase levels. METHODS We evaluated 534 adults with biopsy-proven NAFLD and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <40U/L within 3 months of their liver biopsy. Histological phenotypes of primary interest were nonalcoholic steatohepatitis (NASH) with stage 2-3 fibrosis (NASH F2-3) and cirrhosis. Using multiple logistic regression models with Akaike's Information Criteria (AIC), we identified variables associated with these histological phenotypes. We developed and internally validated their clinical prediction models. RESULTS The prevalence of NASH F2-F3 and cirrhosis was 19% and 7%, respectively. The best multiple regression AIC model for NASH F2-3 consisted of type 2 diabetes, white race, lower low-density lipoprotein, lower platelet count, higher AST/ALT ratio, higher serum triglycerides, and hypertension. The best AIC model for cirrhosis consisted of lower platelet count, lower AST/ALT ratio, higher body mass index, and female sex. The area under the receiver operator curves of the prediction models were 0.70 (95% confidence interval: 0.65-0.76) for detecting NASH-F2-3 and 0.85 (95% confidence interval: 0.77-0.92) for detecting cirrhosis. When models were fixed at maximum Youden's index, their positive and negative predictive values were 35% and 88% for NASH F2-F3 and 30% and 98% for cirrhosis, respectively. DISCUSSION Clinically significant histological phenotypes are observed in patients with NAFLD and normal aminotransferase levels. Our models can assist the clinicians in excluding advanced liver histology in NAFLD patients with normal aminotransferase levels.
The use of technology and sampling frequency to measure variables of tactical positioning in team sports: a systematic review

ABSTRACT The aim of the study was to assess the use of different positioning systems and sampling frequencies to measure spatial-positioning variables in team sports. Articles were selected when the sampling frequency was detailed. 2,194 articles were identified and 59 works were selected for the systematic review. The sampling frequency used to measure tactical behaviour differed considerably among studies. For Global Navigation Satellite System, the sampling frequency ranged from 5- to 15 Hz for raw data, the most commonly used sampling frequency being 5 Hz. For Optic-based tracking systems, the sampling frequency ranged from 10- to 30 Hz. For Local Position System, the sampling frequency ranged from 45- to 100 Hz, the most commonly used sampling frequency being 42 Hz and 57.7 Hz. There is no common criterion in the sampling frequency used to measure each tactical variable. Further studies should investigate the impact of the sampling frequency on the measurement of the tactical variables.
Functional analyses of an axonemal inner‐arm dynein complex in the bloodstream form of Trypanosoma brucei uncover its essential role in cytokinesis initiation

The flagellated eukaryote Trypanosoma brucei alternates between the insect vector and the mammalian host and proliferates through an unusual mode of cell division. Cell division requires flagellum motility‐generated forces, but flagellum motility exerts distinct effects between different life cycle forms. Motility is required for the final cell abscission of the procyclic form in the insect vector, but is necessary for the initiation of cell division of the bloodstream form in the mammalian host. The underlying mechanisms remain elusive. Here we carried out functional analyses of a flagellar axonemal inner‐arm dynein complex in the bloodstream form and investigated its mechanistic role in cytokinesis initiation. We showed that the axonemal inner‐arm dynein heavy chain TbIAD5‐1 and TbCentrin3 form a complex, localize to the flagellum, and are required for viability in the bloodstream form. We further demonstrated the interdependence between TbIAD5‐1 and TbCentrin3 for maintenance of protein stability. Finally, we showed that depletion of TbIAD5‐1 and TbCentrin3 arrested cytokinesis initiation and disrupted the localization of multiple cytokinesis initiation regulators. These findings identified the essential role of an axonemal inner‐arm dynein complex in cell division, and provided molecular insights into the flagellum motility‐mediated cytokinesis initiation in the bloodstream form of T. brucei.
Two Studies of the Impact of Performance Feedback on Community Service Learning Among College Students

TWO STUDIES OF THE IMPACT OF PERFORMANCE FEEDBACK ON COMMUNITY SERVICE LEARNING AMONG COLLEGE STUDENTS In Study 1, I manipulated students' access to frequent written performance feedback from agency supervisors. Thirty-eight service-learning students enrolled in a Midwest university were randomly assigned to a performance feedback (experimental) condition and a no performance feedback (control) condition. Student learning from community service (SLCS) was measured both before and after the semester-long intervention. St~dents in the experimental group did not show significant improvements in SLCS over those in the control condition. However, an individual­ differences variable, feedback disposition predicted SLCS. In study 2, I looked at the impact of organizational feedback quality, client feedback quality, student feedback seeking, and 2 sets of individual-differences variables (goal orientation, and feedback disposition) on SLCS. One hundred seventy-seven students, enrolled in ten service learning classes completed surveys assessing these ariables. Client feedback quality and feedback disposition predicted SLCS significantly.
Psychoeducational Interventions for Adults With Level 3 Autism Spectrum Disorder: A 50-Year Systematic Review

There is face validity to the expectation that adults with level 3 autism spectrum disorder (ASD–3) will benefit from a range of psychoeducational interventions. This paper reviews the empirical evidence supporting the effectiveness of these interventions, many of which are currently used in clinical settings. We reviewed 56 peer-reviewed studies of psychoeducational interventions for adults with ASD–3, written in English and since 1968, that met our criteria. The reviewing team included educators, clinicians, researchers, and a biostatistician. The available literature was limited, and most, if not all, of the studies presented some significant methodological limitations. When using Cochrane’s criteria to assess seven key outcome domains—activities of daily living, aggressive/destructive behaviors, emotional functioning, language/communication skills, self-injurious behaviors, stereotypy/mannerisms, and vocational skills—we found only moderately reliable evidence to support the effectiveness of interventions designed to improve emotional functioning in adults with ASD–3. The reliability of evidence relevant to the six other outcome domains was rated as low or very low. Based on this review, we suggest directions for future study of interventions for adults with ASD–3, including topics, subpopulations, and approaches that should be explored. We also propose some crucial changes in how future studies regarding this population should be designed, analyzed, and documented, while balancing clinical considerations with scientific/educational utility.
Dry Eye Disease: Emerging Approaches to Disease Analysis and Therapy

Dry eye disease (DED) is among the most common ocular disorders affecting tens of millions of individuals worldwide; however, the condition remains incompletely understood and treated. Valuable insights have emerged from multidisciplinary approaches, including immunometabolic analyses, microbiome analyses, and bioengineering. Furthermore, we have seen new developments in clinical assessment approaches and treatment strategies in the recent past. Here, we review the emerging frontiers in the pathobiology and clinical management of DED.
Acellular fish skin matrix on thin-skin graft donor sites: a preliminary study.

OBJECTIVE Surgery for head and neck cancer often requires free flap reconstructions, whose harvesting site often requires a thin-skin graft. Wounds from the thin-skin donor site are comparable to an intermediate or deep second-degree burn. This is uncomfortable and can lead to complications such as a long healing time, local infections and pain. Since they are reproducible, these wounds may serve as a model for an objective assessment of new healing medical devices. The acellular fish skin matrix is a new medical device designed to improve healing quality and time. METHODS We compared the outcomes between standard procedure and the use of this matrix placed on the split-thickness skin graft (STSG) donor site, in patients operated on in our centre for radial forearm free flap reconstruction for head and neck wounds. RESULTS There were 21 patients included. The healing time was halved when using the acellular fish skin matrix, from 68 to 32 days on average. Acellular fish skin matrix reduced pain levels and local infection. The visual analogue pain scale (VAS) was ≥3 at five days (p=0.0034) and infection rate reduced from 60% to 0% (p=0.0039). CONCLUSION These results are extremely encouraging. However, it is important to take into account the relatively high cost of this matrix for its future indications. A larger study including an overall cost estimation and an assessment on different wound types would be interesting, to better target the indications of the acellular fish skin matrix.
Coronary disease is not associated with robust alterations in inflammatory gene expression in human epicardial fat

Epicardial adipose tissue (EAT) is the visceral fat depot of the heart. Inflammation of EAT is thought to contribute to coronary artery disease (CAD). Therefore, we hypothesized that the EAT of patients with CAD would have increased inflammatory gene expression compared with controls without CAD. Cardiac surgery patients with (n = 13) or without CAD (n = 13) were consented, and samples of EAT and subcutaneous adipose tissue (SAT) were obtained. Transcriptomic analysis was performed using Affymetrix Human Gene 1.0 ST arrays. Differential expression was defined as a 1.5-fold change (ANOVA P < 0.05). Six hundred ninety-three genes were differentially expressed between SAT and EAT in controls and 805 in cases. Expression of 326 genes was different between EAT of cases and controls; expression of 14 genes was increased in cases, while 312 were increased in controls. Quantitative reverse transcription PCR confirmed that there was no difference in expression of CCL2, CCR2, TNF-α, IL-6, IL-8, and PAI1 between groups. Immunohistochemistry showed more macrophages in EAT than SAT, but there was no difference in their number or activation state between groups. In contrast to prior studies, we did not find increased inflammatory gene expression in the EAT of patients with CAD. We conclude that the specific adipose tissue depot, rather than CAD status, is responsible for the majority of differential gene expression.