Miracle-dz/UniFAR-FTUs huggingface dataset:
Ciliary Proteins: Filling the Gaps. Recent Advances in Deciphering the Protein Composition of Motile Ciliary Complexes

Cilia are highly evolutionarily conserved, microtubule-based cell protrusions present in eukaryotic organisms from protists to humans, with the exception of fungi and higher plants. Cilia can be broadly divided into non-motile sensory cilia, called primary cilia, and motile cilia, which are locomotory organelles. The skeleton (axoneme) of primary cilia is formed by nine outer doublet microtubules distributed on the cilium circumference. In contrast, the skeleton of motile cilia is more complex: in addition to outer doublets, it is composed of two central microtubules and several diverse multi-protein complexes that are distributed periodically along both types of microtubules. For many years, researchers have endeavored to fully characterize the protein composition of ciliary macro-complexes and the molecular basis of signal transduction between these complexes. Genetic and biochemical analyses have suggested that several hundreds of proteins could be involved in the assembly and function of motile cilia. Within the last several years, the combined efforts of researchers using cryo-electron tomography, genetic and biochemical approaches, and diverse model organisms have significantly advanced our knowledge of the ciliary structure and protein composition. Here, we summarize the recent progress in the identification of the subunits of ciliary complexes, their precise intraciliary localization determined by cryo-electron tomography data, and the role of newly identified proteins in cilia.
Expectations and experiences of hospital postnatal care in the UK: a systematic review of quantitative and qualitative studies

Objectives To report on women’s and families’ expectations and experiences of hospital postnatal care, and also to reflect on women’s satisfaction with hospital postnatal care and to relate their expectations to their actual care experiences. Design Systematic review. Setting UK. Participants Postnatal women. Primary and secondary outcomes Women’s and families’ expectations, experiences and satisfaction with hospital postnatal care. Methods Embase, MEDLINE, PsycINFO, Applied Social Sciences Index and Abstracts, Cumulative Index to Nursing and Allied Health (CINAHL Plus), Science Citation Index, and Social Sciences Citation Index were searched to identify relevant studies published since 1970. We incorporated findings from qualitative, quantitative and mixed-methods studies. Eligible studies were independently screened and quality-assessed using a modified version of the National Institutes of Health Quality Assessment Tool for quantitative studies and the Critical Appraisal Skills Programme for qualitative studies. Data were extracted on participants’ characteristics, study period, setting, study objective and study specified outcomes, in addition to the summary of results. Results Data were included from 53 studies, of which 28 were quantitative, 19 were qualitative and 6 were mixed-methods studies. The methodological quality of the included studies was mixed, and only three were completely free from bias. Women were generally satisfied with their hospital postnatal care but were critical of staff interaction, the ward environment and infant feeding support. Ethnic minority women were more critical of hospital postnatal care than white women. Although duration of postnatal stay has declined over time, women were generally happy with this aspect of their care. There was limited evidence regarding women’s expectations of postnatal care, families’ experience and social disadvantage. Conclusion Women were generally positive about their experiences of hospital postnatal care, but improvements could still be made. Individualised, flexible models of postnatal care should be evaluated and implemented. PROSPERO registration number CRD42017057913.
“I Know, you Know”: Epistemic Egocentrism in Children and Adults

This article reviews the evidence and theory pertaining to a form of perspective-taking failure—a difficulty in setting aside the privileged information that one knows to be unavailable to another party. The authors argue that this bias (epistemic egocentrism, or EE) is a general feature of human cognition and has been tapped by 2 independent and largely uncommunicating research traditions: the theory-of-mind tradition in developmental psychology and, with more sensitive probes, the “heuristics and biases” tradition in the psychology of human judgment. This article sets the stage for facilitating communication between these traditions as well as for the recognition of EE's breadth and potential interdisciplinary significance: The authors propose a life-span account and a tentative taxonomy of EE; and they highlight the interdisciplinary significance of EE by discussing its implications for normative ethics.
Screening key lncRNAs for human lung adenocarcinoma based on machine learning and weighted gene co-expression network analysis.

BACKGROUND Lung adenocarcinoma (LUAD) accounts for a significant proportion of lung cancer and there have been few diagnostic and therapeutic targets for LUAD due to the lack of specific biomarker. The aim of this study was to identify key long non-coding RNAs (lncRNAs) for LUAD. METHODS The lncRNA and mRNA expression profiles of a large group of patients with LUAD were obtained from The Cancer Genome Atlas (TCGA). The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were identified. The optimal diagnostic lncRNA biomarkers for LUAD were identified by using feature selection procedure and classification model. We established classification models including random forests, decision tree and support vector machine to distinguish LUAD and normal tissues. The lncRNAs-mRNAs co-expression networks and module identification were established by weighted gene co-expression network analysis (WGCNA). Functional annotation of pink and green modules was performed. The expression of selected DElncRNAs were validated by qRT-PCR. RESULTS A total of 1364 DEmRNAs (468 down-regulated and 896 up-regulated mRNAs) and 260 DElncRNAs (88 down-regulated and 172 up-regulated lncRNAs) between LUAD and normal tissue were obtained. LANCL1-AS1, MIR3945HG, LINC01270, RP5-1061H20.4, BLACAT1, LINC01703, CTD-2227E11.1 and RP1-244F24.1 were identified as optimal diagnostic lncRNA biomarkers for LUAD. The area under curve (AUC) of the random forests model, decision tree model and SVM model were 0.999, 0.937 and 0.999, and the specificity and sensitivity of the three model were 98.3% and 99.8%, 93.2% and 99% and 100% and 98.4%, respectively. Co-expression networks analysis showed that RP11-389C8.2, CTD-2510F5.4 and TMPO-AS1 were co-expressed with 44, 242 and 241 mRNAs, respectively. Cell cycle, DNA replication and p53 signaling pathway were three significantly enriched pathways. The qRT-PCR results were consistent with our integrated analysis, generally. The GSE32863 and GSE104854 validation was consistent with our integrated analysis, generally. CONCLUSION Our study identified eight DElncRNAs as potential diagnostic biomarkers of LUAD. Functional annotation of green module provided new evidences for exploring the precise roles of lncRNA in LUAD.
Geographic Access to Preexposure Prophylaxis Clinics Among Men Who Have Sex With Men in the United States.

Objectives. To explore US geographic areas with limited access to HIV preexposure prophylaxis (PrEP) providers, PrEP deserts. Methods. We sourced publicly listed PrEP providers from a national database of PrEP providers from 2017 and obtained county-level urbanicity classification and population estimates of men who have sex with men (MSM) from public data. We calculated travel time from census tract to the nearest provider. We classified a census tract as a PrEP desert if 1-way driving time was greater than 30 or 60 minutes. Results. One in 8 PrEP-eligible MSM (108 758/844 574; 13%) lived in 30-minute-drive deserts, and a sizable minority lived in 60-minute-drive deserts (38 804/844 574; 5%). Location in the South and lower urbanicity were strongly associated with increased odds of PrEP desert status. Conclusions. A substantial number of persons at high risk for HIV transmission live in locations with no nearby PrEP provider. Rural and Southern areas are disproportionately affected. Public Health Implications. For maximum implementation effectiveness of PrEP, geography should not determine access. Programs to train clinicians, expand venues for PrEP care, and provide telemedicine services are needed. (Am J Public Health. Published online ahead of print July 18, 2019: e1-e8. doi:10.2105/AJPH.2019.305172).
Effects of Social Support and 12-Step Involvement on Recovery among People in Continuing Care for Cocaine Dependence

Abstract Background: Social networks that support recovery lead to enhanced treatment outcomes and sobriety regardless if this support stems from family, peer groups or 12-Step programs. Treatment process factors including readiness to change and commitment to abstinence also impact substance use. However, little is understood about the relationship between social support to treatment process factors during and after treatment for substance use disorders. Objectives: To identify the ways in which different social networks foster substance use change in a sample of individuals with cocaine dependence from intensive outpatient programs (IOPs). Methods: Data were drawn from two studies examining adults (N = 489) with cocaine dependence in IOPs for substance use disorders collected between 2004 and 2009. Assessment data were collected at 3- to 6-month intervals from baseline to 24-months and included the University of Rhode Island change assessment questionnaire, timeline followback, thoughts about abstinence, perceived social support – friend, and family versions and analyzed using GEE and mediational analyses. Results: Greater perceived friend social support was associated with greater readiness to change whereas greater perceived familial social support was associated with substance use goal; greater social support from both friends and family were associated with less substance use. Greater AA/NA participation was associated with substance use goal and readiness to change, and less substance use. Substance use goals partially mediated the impact of social support on later substance use. Conclusions/Importance: While peer and familial support are key to sustained recovery, their impact differentially affects treatment process variables. This information could be used to inform social support treatment interventions.
Dermatitis among workers in Ontario: results from the Occupational Disease Surveillance System

Objectives Dermatitis is the most common occupational skin disease, and further evidence is needed regarding preventable risk factors. The Occupational Disease Surveillance System (ODSS) derived from administrative data was used to investigate dermatitis risk among industry and occupation groups in Ontario. Methods ODSS cohort members were identified from Workplace Safety and Insurance Board (WSIB) accepted lost time claims. A case was defined as having ≥2 dermatitis physician billing claims during a 12-month period within 3 years of cohort entry. A 3-year look-back period prior to cohort entry was used to exclude prevalent cases without a WSIB claim. Workers were followed for 3 years or until dermatitis diagnosis, age 65 years, emigration, death or end of follow-up (31 December 2016), whichever occurred first. Age-adjusted and sex-adjusted Cox proportional hazard models estimated HRs and 95% CIs. The risk of dermatitis was explored using a job exposure matrix that identifies exposure to asthmagens, many of which also cause contact dermatitis. Results Among 597 401 workers, 23 843 cases of new-onset dermatitis were identified. Expected elevated risks were observed among several groups including furniture and fixture industries, food and beverage preparation and chemicals, petroleum, rubber, plastic and related materials processing occupations and workers exposed to metal working fluids and organic solvents. Decreased risk was observed among farmers, nurses and construction industries, and occupations exposed to latex and indoor cleaning products. Conclusions ODSS can contribute to occupational dermatitis surveillance in Ontario by identifying occupational groups at risk of dermatitis that can then be prioritised for prevention activities.
Evaluation of a Free Public Smartphone Application to Detect Leukocoria in High-Risk Children Aged 1 to 6 Years.

PURPOSE To determine whether a white-eye detector smartphone application (app) can be used as a screening tool to detect early signs of leukocoria in a clinical practice. METHODS A prospective, single-visit study of children aged 1 to 6 years presenting to the University Eye Clinic of Genova for a complete pediatric ophthalmologic examination was conducted. All children who met the enrollment criteria were screened by an orthoptist with the CRADLE (Computer Assisted Detector of Leukocoria) smartphone app for an iPhone operating system (iOS) (iPhone 7; Apple, Cupertino, CA). Cycloplegic retinoscopy and fundus examination were performed 30 minutes after one to two drops of a pediatric combination drop, comprising tropicamide 1% and phenylephrine 2.5%, were instilled. A comparison between the two methods yielded sensitivity, specificity, and negative likelihood ratio values. RESULTS A total of 244 eyes of 122 children were included in the study. Nine eyes of 244 (3.6%) had leukocoria evaluable by penlight caused by amblyogenic cataract, 1 (0.4%) patient had retinopathy of prematurity stage 5, and 3 (1.2%) patients had retinoblastoma. The sensitivity of the white-eye detector app was 15.38% (95% confidence interval [CI]: 1.92% to 45.45%), the specificity was 100% (95% CI: 98.48% to 100.00%), and the negative likelihood ratio was 0.85 (95% CI: 0.67 to 1.07). CONCLUSIONS A smartphone photoscreening app able to detect leukocoria may provide valuable support for children's parents. However, it cannot be considered an alternative to the ophthalmoscope for children. [J Pediatr Ophthalmol Strabismus. 2019;56(4):229-232. ].
The interindividual variability of transcranial magnetic stimulation effects: Implications for diagnostic use in movement disorders

A large number of methods have been described that use transcranial magnetic stimulation to probe the physiology of the human motor cortex. Since the 1990s, hundreds of papers have used them to investigate neurophysiological signatures of different types of movement disorders. However, in recent years there has been increasing recognition of the interindividual variability of these measures and a focus on estimating their reliability and reproducibility. Although this work has been carried out in healthy individuals, it is highly relevant to movement disorders because it may impact the validity of some accepted (“canonical”) neurophysiological biomarkers. The aim of this review is to reexamine the diagnostic usefulness of transcranial magnetic stimulation methods in movement disorders in the context of present knowledge of methodological variability.
Assembling a plug-and-play production line for combinatorial biosynthesis of aromatic polyketides in Escherichia coli

Polyketides are a class of specialised metabolites synthesised by both eukaryotes and prokaryotes. These chemically and structurally diverse molecules are heavily used in the clinic and include frontline antimicrobial and anticancer drugs such as erythromycin and doxorubicin. To replenish the clinicians’ diminishing arsenal of bioactive molecules, a promising strategy aims at transferring polyketide biosynthetic pathways from their native producers into the biotechnologically desirable host Escherichia coli. This approach has been successful for type I modular polyketide synthases (PKSs); however, despite more than 3 decades of research, the large and important group of type II PKSs has until now been elusive in E. coli. Here, we report on a versatile polyketide biosynthesis pipeline, based on identification of E. coli–compatible type II PKSs. We successfully express 5 ketosynthase (KS) and chain length factor (CLF) pairs—e.g., from Photorhabdus luminescens TT01, Streptomyces resistomycificus, Streptoccocus sp. GMD2S, Pseudoalteromonas luteoviolacea, and Ktedonobacter racemifer—as soluble heterodimeric recombinant proteins in E. coli for the first time. We define the anthraquinone minimal PKS components and utilise this biosynthetic system to synthesise anthraquinones, dianthrones, and benzoisochromanequinones (BIQs). Furthermore, we demonstrate the tolerance and promiscuity of the anthraquinone heterologous biosynthetic pathway in E. coli to act as genetically applicable plug-and-play scaffold, showing it to function successfully when combined with enzymes from phylogenetically distant species, endophytic fungi and plants, which resulted in 2 new-to-nature compounds, neomedicamycin and neochaetomycin. This work enables plug-and-play combinatorial biosynthesis of aromatic polyketides using bacterial type II PKSs in E. coli, providing full access to its many advantages in terms of easy and fast genetic manipulation, accessibility for high-throughput robotics, and convenient biotechnological scale-up. Using the synthetic and systems biology toolbox, this plug-and-play biosynthetic platform can serve as an engine for the production of new and diversified bioactive polyketides in an automated, rapid, and versatile fashion.
Imaging tools to map in vivo the human brain

Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Neurology Division, Department of Medicine, Toronto Western Hospital, University Health Network (UNH), University of Toronto, Ontario, Canada Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada Division of Brain, Imaging and Behaviour–Systems Neuroscience, Krembil Research Institute, UHN, University of Toronto, Ontario, Canada
Value of in vivo α‐synuclein deposits in Parkinson's disease: A systematic review and meta‐analysis

Previous studies that have investigated the potential of in vivo abnormal α‐synuclein deposits as a pathological biomarker for PD included few participants and reported different diagnostic accuracies. Here, we aimed to confirm the diagnostic value of in vivo α‐synuclein deposits in PD through a systematic review and meta‐analysis, with special emphasis on determining the tissue most suitable for examination and assessing whether anti‐native α‐synuclein or anti‐phosphorylated α‐synuclein antibodies should be used. Databases were searched on December 30, 2018. We finally included 41 case‐control studies that examined in vivo tissue samples using anti‐native α‐synuclein or anti‐phosphorylated α‐synuclein antibody in PD patients and controls. Using a univariate random‐effects model, pooled sensitivity and specificity (95% confidence interval) of anti‐native α‐synuclein antibody were 0.54 (0.49‐0.60) and 0.72 (0.68‐0.76) for the gastrointestinal tract and 0.76 (0.60‐0.89) and 0.60 (0.43‐0.74) for the skin. Pooled sensitivity and specificity (95% confidence interval) of anti‐phosphorylated α‐synuclein antibody were 0.43 (0.37‐0.48) and 0.82 (0.78‐0.86) for the gastrointestinal tract, 0.76 (0.69‐0.82) and 1.00 (0.98‐1.00) for the skin, 0.42 (0.26‐0.59) and 0.94 (0.84‐0.99) for the minor salivary glands, and 0.66 (0.51‐0.79) and 0.96 (0.86‐1.00) for the submandibular glands. Although ubiquitous heterogeneity between the included studies should be noted when interpreting our results, our analyses demonstrated the following: (1) in vivo α‐synuclein immunoreactivity has the potential as a pathological biomarker for PD; (2) anti‐phosphorylated α‐synuclein antibody consistently has higher specificity than anti‐native α‐synuclein antibody; and (3) skin biopsy examination using anti‐phosphorylated α‐synuclein antibody has the best diagnostic accuracy, although feasibility remains an important issue. © 2019 International Parkinson and Movement Disorder Society
Depressed Myocardial Energetic Efficiency Increases Risk of Incident Heart Failure: The Strong Heart Study

An estimation of myocardial mechano-energetic efficiency (MEE) per unit of left ventricular (LV) mass (MEEi) can significantly predict composite cardiovascular (CV) events in treated hypertensive patients with normal ejection fraction (EF), after adjustment for LV hypertrophy (LVH). We have tested whether MEEi predicts incident heart failure (HF), after adjustment for LVH, in the population-based cohort of a “Strong Heart Study” (SHS) with normal EF. We included 1912 SHS participants (age 59 ± 8 years; 64% women) with preserved EF (≥50%) and without prevalent CV disease. MEE was estimated as the ratio of stroke work to the “double product” of heart rate times systolic blood pressure. MEEi was calculated as MEE/LV mass, and analyzed in quartiles. During a follow-up study of 9.2 ± 2.3 years, 126 participants developed HF (7%). HF was preceded by acute myocardial infarction (AMI) in 94 participants. A Kaplan-Meier plot, in quartiles of MEEi, demonstrated significant differences, substantially due to the deviation of the lowest quartile (p < 0.0001). Using AMI as a competing risk event, sequential models of Cox regression for incident HF (including significant confounders), demonstrated that low MEEi predicted incident HF not due to AMI (p = 0.026), after adjustment for significant effect of age, LVH, prolonged LV relaxation, diabetes, and smoking habits with negligible effects for sex, hypertension, antihypertensive therapy, obesity, and hyperlipemia. Low LV mechano-energetic efficiency per unit of LVM, is a predictor of incident, non-AMI related, HF in subjects with initially normal EF.
Diagnostic Classification of Bronchopulmonary Dysplasia: A Compromise between Defining Lung Disease versus Long-Term Outcome Prediction

the relative contributions that specific AM subtypes made to the overall transcriptional signal, our ability to detect differentially expressed genes may have been weakened. Despite this limitation, our bulk transcriptomic approach has advanced our understanding of AM function in ARDS by identifying AM-specific genetic programs that were associated with good versus poor outcomes. Future work is needed to identify the AM subtypes that might be responsible for the bulk transcriptional signatures we identified in our clinical cohort. We believe that “lumping” and “splitting” approaches are complementary in furthering our understanding of the pathobiology of syndromes such as ARDS and sepsis. Analytical approaches such as cellular deconvolution (7) may be able to bridge bulk transcriptomic datasets and clinical cohorts like ours with highly granular single-cell datasets to fully leverage the strengths of both lumping and splitting approaches to understand the mechanisms of complex human syndromes. n
The Humoral Immune Response Against the gB Vaccine: Lessons Learnt from Protection in Solid Organ Transplantation

Human cytomegalovirus (hCMV) is considered to be the highest priority for vaccine development. This view is underscored by the significant morbidity associated with congenital hCMV infection and viraemia in transplant patients. Although a number of vaccines have been trialed, none have been licensed. The hCMV vaccine candidate that has performed best in clinical trials to date is the recombinant glycoprotein B (gB) vaccine that has demonstrated protection, ranging from a 43% to 50% efficacy in three independent phase II trials. In this review, we focus on data from the phase II trial performed in solid organ transplant patients and the outcomes of follow-up studies attempting to identify immunological and mechanistic correlates of protection associated with this vaccine strategy. We relate this to other vaccine studies of gB as well as other vaccine strategies to determine areas of commonality and divergence. Finally, through the review, we discuss the unique challenges and opportunities presented with vaccine studies in transplant populations with recommendations that could empower subsequent trials.