Miracle-dz/UniFAR-FTUs huggingface dataset:
Faculty development: From rubies to oak

Abstract Introduction: Faculty development has played a significant role in health professions education over the last 40 years. The goal of this perspective is to present a portrait of faculty development in Medical Teacher since its inception and to highlight emerging trends moving forward. Method: All issues of Medical Teacher were reviewed, using the search terms faculty development, staff development, professional development, or in-service training for faculty. The search yielded 286 results of which 145 focused specifically on faculty development initiatives, reviews, or frameworks. Findings: This review demonstrated a significant growth in publications related to faculty development in Medical Teacher over the last 40 years, with a primary focus on teaching improvement and traditional approaches to faculty development, including workshops, short courses and other structured, group activities. The international nature of faculty development was also highlighted. Recommendations: Moving forward, it is suggested that we: broaden the scope of faculty development from teaching to academic development; expand our approaches to faculty development, to include peer coaching, workplace learning and communities of practice; utilize a competency-based framework to guide the development of faculty development curricula; support teachers’ professional identities through faculty development; focus on organizational development and change; and rigorously promote research and scholarship in faculty development.
Complete Chloroplast Genomes of Vachellia nilotica and Senegalia senegal: Comparative Genomics and Phylogenomic Placement in a New Generic System

Vachellia and Senegalia are the most important genera in the subfamily Mimosoideae (Fabaceae). Recently, species from both genera were separated from the long-characterized Acacia due to their macro-morphological characteristics. However, this morpho-taxonomic differentiation struggles to discriminate some species, for example, Vachellia nilotica and Senegalia senegal. Therefore, sequencing the chloroplast (cp) genomes of these species and determining their phylogenetic placement via conserved genes may help to validate the taxonomy. Hence, we sequenced the cp genomes of V. nilotica and S. senegal, and the results showed that the sizes of the genomes are 165.3 and 162.7 kb, respectively. The cp genomes of both species comprised large single-copy regions (93,849~91,791 bp) and pairs of inverted repeats (IR; 26,093~26,008 bp). The total numbers of genes found in the V. nilotica and S. senegal cp genomes were 135 and 132, respectively. Approximately 123:130 repeats and 290:281 simple sequence repeats were found in the S. senegal and V. nilotica cp genomes, respectively. Genomic characterization was undertaken by comparing these genomes with those of 17 species belonging to related genera in Fabaceae. A phylogenetic analysis of the whole genome dataset and 56 shared genes was undertaken by generating cladograms with the same topologies and placing both species in a new generic system. These results support the likelihood of identifying segregate genera from Acacia with phylogenomic disposition of both V. nilotica and S. senegal in the subfamily Mimosoideae. The current study is the first to obtain complete genomic information on both species and may help to elucidate the genome architecture of these species and evaluate the genetic diversity among species.
The impact of language on the interpretation of resuscitation clinical care plans by doctors. A mixed methods study

Introduction Resuscitation clinical care plans (resuscitation plans) are gradually replacing ‘Not for Cardiopulmonary Resuscitation’ orders in the hospital setting. The 7-Step Pathway Resuscitation Plan and Alert form (7-Step form) is one example of a resuscitation plan. Treatment recommendations in resuscitation plans currently lack standardised language, creating potential for misinterpretation and patient harm. Aims To explore how terminology used in resuscitation plans is interpreted and applied by clinicians. Method A mixed methods study surveyed 50 general medical doctors, who were required to interpret and apply a 7-Step form in three case vignettes and define seven key terms. Statistical analysis on multiple choice and thematic analysis on free-text responses was performed. Results Terminology was inconsistently interpreted and inconsistently applied, resulting in clinically significant differences in treatment choices. Three key themes influenced the application of a resuscitation plan: in-depth discussion, precise documentation and personal experience of the bedside deciding doctor. Discussion This study highlights persistent communication deficiencies in resuscitation plan documentation and how this may adversely affect patient care; findings unlikely to be unique to Australia or South Australia. Conclusion Removing ambiguity by standardising and defining the terminology in resuscitation plans will improve bedside decision-making, while also supporting the rights of the patient to receive appropriate and desired care.
Diagnostic Challenges Associated with GLUT1 Deficiency: Phenotypic Variabilities and Evolving Clinical Features

GLUT1 deficiency is a rare neurometabolic disorder that can be effectively treated with ketogenic diet. However, this condition is underdiagnosed due to its nonspecific, overlapping, and evolving symptoms with age. We retrospectively reviewed the clinical course of nine patients diagnosed with GLUT1 deficiency, based on SLC2A1 mutations and/or glucose concentration in cerebrospinal fluid. The patients included eight boys and one girl who initially presented with seizures (44%, 4/9) or delayed development (44%, 4/9) before 2 years of age, except for one patient who presented with apnea as a neonate. Over the clinical course, all of the children developed seizures of the mixed type, including absence seizures and generalized tonic–clonic seizures. About half (56%, 5/9) showed movement disorders such as ataxia, dystonia, or dyskinesia. We observed an evolution of phenotype over time, although this was not uniform across all patients. Only one child had microcephaly. In five patients, ketogenic diet was effective in reducing seizures and movement symptoms, and the patients exhibited subjective improvement in cognitive function. Diagnosing GLUT1 deficiency can be challenging due to the phenotypic variability and evolution. A high index of clinical suspicion in pediatric and even older patients with epilepsy or movement disorders is key to the early diagnosis and treatment, which can improve the patient's quality of life.
Crosstalk between miR‐215 and epithelial‐mesenchymal transition specific markers (E‐cadherin and N‐cadherin) in different stages of chronic HCV Infection

The main causes of death among patients with hepatocellular carcinoma (HCC) are a recurrence, metastasis, and deterioration of primary tumors by the epithelial‐to‐mesenchymal transition (EMT) which is controlled by several molecules including E‐cadherin and N‐cadherin. Microribonucleic acids (miRNAs) have been identified to play a regulatory role in EMT. miR‐215 is important in repressing migration/invasion of cancer cells. In this study, we aimed to evaluate the crosstalk between miR‐215 and EMT specific markers (E‐cadherin and N‐cadherin) with a spotlight on its role in the EMT process in hepatitis C virus (HCV)‐infected patients. One hundred forty‐five patients were studied, 75 had HCV‐induced cirrhosis classified into child A, B, and C and 25 had HCC. In parallel, 45 healthy volunteers considered as controls. Serum levels of E‐ and N‐cadherin were measured using enzyme‐linked immunosorbent assay and miR‐215 expression measured by a quantitative reverse transcription‐polymerase chain reaction. Insignificant change in serum levels of E‐cadherin and N‐cadherin in HCV‐infected patients compared with normal controls was observed with a slight increase in E‐cadherin and N‐cadherin in the child B group. HCC patients had the lowest amount of E‐cadherin and N‐cadherin compared with cirrhotic and normal subjects. A maximum reduction in miR‐215 was observed in HCC patients compared with cirrhotic and control ones. A positive correlation (r = .202; P < .05) was observed between miR‐215 and E‐cadherin. Our data stressed on the potential role of miR‐215 as an important mediator in HCC progression. miRNAs participating in EMT needs further studies to provide insight into the metastasis of HCC.
Normative values for relative schoolbag weight in primary school children aged 6-14 from Czech Republic: A pilot study

Little evidence from observational studies has been provided regarding ‘optimal’ relative schoolbag load during primary education. Also, no study to date has provided reference-based standards for relative schoolbag weight. Therefore, the main purpose of the study was to establish normative values of relative schoolbag weight in a sample of children. In this cross-sectional study, we recruited 584 primary school students aged 6–14 (meanage±SD = 9.6±2.4 yrs, meanheight±SD = 1.4±0.2 m, meanweight±SD = 37.5±13.3 kg, meanbody-mass index±SD = 17.6±3.1 kg/m2, 44.4% girls) chosen from five schools in the city of Brno. Schoolbag weight and child’s body weight were objectively measured by using digital scale. Relative schoolbag weight was calculated by dividing schoolbag weight with child’s body weight and the result was expressed in percentage. Lambda, Mu and Sigma (LMS) method was used to create sex- and age-percentile curves. Boys carried slightly heavier schoolbag, compared with girls (mean difference 0.2 kg, p = 0.020). No significant differences between sexes in relative schoolbag weight were observed (p = 0.240). Median values (P50) for boys and girls were similar and the largest observed between ages 6–9 in boys (15–17%) and 6–8 in girls (16–18%). The percentage of children carrying relative schoolbag weight beyond 10% of their body weight was very high, especially between ages 6–10 in boys (85.1–100%) and 6–11 in girls (86.8–95.4%). This study provides first sex- and age- relative schoolbag weight normative values in primary school children. Future studies should use similar methods for generating comparable data.
The Expression of BNP, ET-1, and TGF-β1 in Myocardium of Rats with Ventricular Arrhythmias

Ventricular arrhythmia (VA) is a major component of sudden cardiac death (SCD). To investigate the expression of brain natriuretic peptide (BNP), endothelin-1 (ET-1), and transforming growth factor-beta 1 (TGF-β1) during VA, we established a rat model of VA induced by BaCl2 solution through a microinjector pump. PD142893 (ET-1 receptor blocker) and SB431542 (TGF-β1 receptor type I blocker) were used to explore the effect of ET-1 and TGF-β1 on BNP expression in the myocardium after VA. BNP, ET-1, and TGF-β1 in rat myocardium were assayed by western blot and immunohistochemical staining for proteins, and real-time quantitative polymerase chain reaction for mRNAs. We found increased expression of BNP and ET-1 in rat myocardium that was associated with the duration of VA. However, TGF-β1 protein expression remained unchanged. Such early increases in BNP and ET-1 may be attributed to fatal arrhythmias associated with SCD, suggesting these may be novel biomarkers of this disease. After intraperitoneal injection of PD142893 and SB431542, respectively, BNP was downregulated in the myocardium of the left ventricle; however, this was abrogated by co-application of the two inhibitors. These results suggested that both ET-1 and TGF-β1, by specifically binding to their receptors, might be involved in the myocardial synthesis of BNP during VA in vivo.
Therapeutic Potential of AAV1-Rheb(S16H) Transduction Against Alzheimer’s Disease

We recently reported that adeno-associated virus serotype 1-constitutively active Ras homolog enriched in brain [AAV1-Rheb(S16H)] transduction of hippocampal neurons could induce neuron-astroglia interactions in the rat hippocampus in vivo, resulting in neuroprotection. However, it remains uncertain whether AAV1-Rheb(S16H) transduction induces neurotrophic effects and preserves the cognitive memory in an animal model of Alzheimer’s disease (AD) with characteristic phenotypic features, such as β-amyloid (Aβ) accumulation and cognitive impairments. To assess the therapeutic potential of Rheb(S16H) in AD, we have examined the beneficial effects of AAV1-Rheb(S16H) administration in the 5XFAD mouse model. Rheb(S16H) transduction of hippocampal neurons in the 5XFAD mice increased the levels of neurotrophic signaling molecules, including brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF), and their corresponding receptors, tropomyosin receptor kinase B (TrkB) and CNTF receptor α subunit (CNTFRα), respectively. In addition, Rheb(S16H) transduction inhibited Aβ production and accumulation in the hippocampus of 5XFAD mice and protected the decline of long-term potentiation (LTP), resulting in the prevention of cognitive impairments, which was demonstrated using novel object recognition testing. These results indicate that Rheb(S16H) transduction of hippocampal neurons may have therapeutic potential in AD by inhibiting Aβ accumulation and preserving LTP associated with cognitive memory.
Low Dose Low-Molecular-Weight Heparin for Thrombosis Prophylaxis: Systematic Review with Meta-Analysis and Trial Sequential Analysis

International guidelines recommend low-molecular-weight heparin (LMWH) as first-line pharmacological option for the prevention of venous thromboembolism (VTE) in many patient categories. Guidance on the optimal prophylactic dose is lacking. We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials to assess benefits and harms of low-dose LMWH versus placebo or no treatment for thrombosis prophylaxis in patients at risk of VTE. PubMed, Cochrane Library, Web of Science, and Embase were searched up to June 2019. Results were presented as relative risk (RR) with conventional and TSA-adjusted confidence intervals (CI). Forty-four trials with a total of 22,579 participants were included. Six (14%) had overall low risk of bias. Low-dose LMWH was not statistically significantly associated with all-cause mortality (RR 0.99; 95%CI 0.85–1.14; TSA-adjusted CI 0.89–1.16) but did reduce symptomatic VTE (RR 0.62; 95%CI 0.48–0.81; TSA-adjusted CI 0.44–0.89) and any VTE (RR 0.61; 95%CI 0.50–0.75; TSA-adjusted CI 0.49–0.82). Analyses on major bleeding (RR 1.07; 95%CI 0.72–1.59), as well as serious adverse events (SAE) and clinically relevant non-major bleeding were inconclusive. There was very low to moderate-quality evidence that low-dose LMWH for thrombosis prophylaxis did not decrease all-cause mortality but reduced the incidence of symptomatic and asymptomatic VTE, while the analysis of the effects on bleeding and adverse events remained inconclusive.
Long-term Monocular Deprivation during Juvenile Critical Period Disrupts Binocular Integration in Mouse Visual Thalamus

Study of the neural deficits caused by mismatched binocular vision in early childhood has predominantly focused on circuits in the primary visual cortex (V1). Recent evidence has revealed that neurons in mouse dorsolateral geniculate nucleus (dLGN) can undergo rapid ocular dominance plasticity following monocular deprivation (MD). It remains unclear, however, whether the long-lasting deficits attributed to MD during the critical period originate in the thalamus. Using in vivo two-photon Ca2+ imaging of dLGN afferents in superficial layers of V1 in female and male mice, we demonstrate that 14 d MD during the critical period leads to a chronic loss of binocular dLGN inputs while sparing response strength and spatial acuity. Importantly, MD leads to profoundly mismatched visual tuning properties in remaining binocular dLGN afferents. Furthermore, MD impairs binocular modulation, reducing facilitation of responses of both binocular and monocular dLGN inputs during binocular viewing. As predicted by our findings in thalamic inputs, Ca2+ imaging from V1 neurons revealed spared spatial acuity but impaired binocularity in L4 neurons. V1 L2/3 neurons in contrast displayed deficits in both binocularity and spatial acuity. Our data demonstrate that critical-period MD produces long-lasting disruptions in binocular integration beginning in early binocular circuits in dLGN, whereas spatial acuity deficits first arise from circuits further downstream in V1. Our findings indicate that the development of normal binocular vision and spatial acuity depend upon experience-dependent refinement of distinct stages in the mammalian visual system. SIGNIFICANCE STATEMENT Abnormal binocular vision and reduced acuity are hallmarks of amblyopia, a disorder that affects 2%–5% of the population. It is widely thought that the neural deficits underlying amblyopia begin in the circuits of primary visual cortex. Using in vivo two-photon calcium imaging of thalamocortical axons in mice, we show that depriving one eye of input during a critical period in development chronically impairs binocular integration in thalamic inputs to primary visual cortex. In contrast, visual acuity is spared in thalamic inputs. These findings shed new light on the role for developmental mechanisms in the thalamus in establishing binocular vision and may have critical implications for amblyopia.
Increasing knowledge of HIV status in a country with high HIV testing coverage: Results from the Botswana Combination Prevention Project

Introduction Achieving widespread knowledge of HIV-positive status is a crucial step to reaching universal ART coverage, population level viral suppression, and ultimately epidemic control. We implemented a multi-modality HIV testing approach to identify 90% or greater of HIV-positive persons in the Botswana Combination Prevention Project (BCPP) intervention communities. Methods BCPP is a cluster-randomized trial designed to evaluate the impact of combination prevention interventions on HIV incidence in 30 communities in Botswana. Community case finding and HIV testing that included home and targeted mobile testing were implemented in the 15 intervention communities. We described processes for identifying HIV-positive persons, uptake of HIV testing by age, gender and venue, characteristics of persons newly diagnosed through BCPP, and coverage of knowledge of status reached at the end of study. Results Of the 61,655 eligible adults assessed in home or mobile settings, 13,328 HIV-positive individuals, or 93% of the estimated 14,270 positive people in the communities were identified through BCPP. Knowledge of status increased by 25% over the course of the study with the greatest increases seen among men (37%) as compared to women (19%) and among youth aged 16–24 (77%) as compared to older age groups (21%). Although more men were tested through mobile than through home-based testing, higher rates of newly diagnosed HIV-positive men were found through home than mobile testing. Conclusions Even when HIV testing coverage is high, additional gains can be made using a multi-modality HIV testing strategy to reach different sub-populations who are being missed by non-targeted program activities. Men and youth can be reached and will engage in community testing when services are brought to places they access routinely.
STK-12 acts as a transcriptional brake to control the expression of cellulase-encoding genes in Neurospora crassa

Cellulolytic fungi have evolved a complex regulatory network to maintain the precise balance of nutrients required for growth and hydrolytic enzyme production. When fungi are exposed to cellulose, the transcript levels of cellulase genes rapidly increase and then decline. However, the mechanisms underlying this bell-shaped expression pattern are unclear. We systematically screened a protein kinase deletion set in the filamentous fungus Neurospora crassa to search for mutants exhibiting aberrant expression patterns of cellulase genes. We observed that the loss of stk-12 (NCU07378) caused a dramatic increase in cellulase production and an extended period of high transcript abundance of major cellulase genes. These results suggested that stk-12 plays a critical role as a brake to turn down the transcription of cellulase genes to repress the overexpression of hydrolytic enzymes and prevent energy wastage. Transcriptional profiling analyses revealed that cellulase gene expression levels were maintained at high levels for 56 h in the Δstk-12 mutant, compared to only 8 h in the wild-type (WT) strain. After growth on cellulose for 3 days, the transcript levels of cellulase genes in the Δstk-12 mutant were 3.3-fold over WT, and clr-2 (encoding a transcriptional activator) was up-regulated in Δstk-12 while res-1 and rca-1 (encoding two cellulase repressors) were down-regulated. Consequently, total cellulase production in the Δstk-12 mutant was 7-fold higher than in the WT. These results strongly suggest that stk-12 deletion results in dysregulation of the cellulase expression machinery. Further analyses showed that STK-12 directly targets IGO-1 to regulate cellulase production. The TORC1 pathway promoted cellulase production, at least partly, by inhibiting STK-12 function, and STK-12 and CRE-1 functioned in parallel pathways to repress cellulase gene expression. Our results clarify how cellulase genes are repressed at the transcriptional level during cellulose induction, and highlight a new strategy to improve industrial fungal strains.
Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile

Objectives Determine global skin transcriptome patterns of early diffuse systemic sclerosis (SSc) and how they differ from later disease. Methods Skin biopsy RNA from 48 patients in the Prospective Registry for Early Systemic Sclerosis (PRESS) cohort (mean disease duration 1.3 years) and 33 matched healthy controls was examined by next-generation RNA sequencing. Data were analysed for cell type-specific signatures and compared with similarly obtained data from 55 previously biopsied patients in Genetics versus Environment in Scleroderma Outcomes Study cohort with longer disease duration (mean 7.4 years) and their matched controls. Correlations with histological features and clinical course were also evaluated. Results SSc patients in PRESS had a high prevalence of M2 (96%) and M1 (94%) macrophage and CD8 T cell (65%), CD4 T cell (60%) and B cell (69%) signatures. Immunohistochemical staining of immune cell markers correlated with the gene expression-based immune cell signatures. The prevalence of immune cell signatures in early diffuse SSc patients was higher than in patients with longer disease duration. In the multivariable model, adaptive immune cell signatures were significantly associated with shorter disease duration, while fibroblast and macrophage cell type signatures were associated with higher modified Rodnan Skin Score (mRSS). Immune cell signatures also correlated with skin thickness progression rate prior to biopsy, but did not predict subsequent mRSS progression. Conclusions Skin in early diffuse SSc has prominent innate and adaptive immune cell signatures. As a prominently affected end organ, these signatures reflect the preceding rate of disease progression. These findings could have implications in understanding SSc pathogenesis and clinical trial design.