Miracle-dz/UniFAR-FTUs huggingface dataset:
Setting the scene for the Second Stroke Recovery and Rehabilitation Roundtable

The Stroke Recovery and Rehabilitation Roundtable (SRRR) meetings bring together an international group of preclinical and clinical researchers along with statisticians, methodologists, funders and consumers, working to accelerate the development of effective treatments for stroke recovery and to support best-evidence uptake in rehabilitation practice. The first meeting (2016) focused on four recommendation areas: translation of preclinical evidence into human discovery trials; recovery biomarkers to provide knowledge of therapeutic targets and prognosis in human stroke; intervention development, monitoring, and reporting standards; and standardized measurement in motor recovery trials. The impact of SRRR is growing, with uptake of recommendations emerging, and funders exploring ways to incorporate research targets and recommendations. At our second meeting (SRRR2, 2018), we worked on new priority areas: (1) cognitive impairment, (2) standardizing metrics for measuring quality of movement, (3) improving development of recovery trials, and (4) moving evidence-based treatments into practice. To accelerate progress towards breakthrough treatments, formation of an International Stroke Recovery and Rehabilitation Alliance is our next step, where working groups will take recommendations and build partnerships needed to achieve our goals.
Clinical pattern of tuberculous adenitis in Qatar: Experience with 35 patients

A prospective observational study was conducted to describe the clinical presentation, diagnostic yield of fine-needle aspiration (FNA) cytology and lymph node biopsy and the outcome of tuberculous (TB) adenitis in patients admitted to Hamad General Hospital, Qatar, between 1 January and 31 December 2006. TB adenitis that was predominantly cervical was confirmed in 35 patients (28M, 7F) with a mean age of 29.4±9 y. Of the 35 cases, caseating granulomata were confirmed by FNA in 20, by lymph node biopsy following negative FNA in 9, and by biopsy alone in 6. Mycobacterium tuberculosis was cultured from FNA alone in 24 cases, in 9 cases from biopsies after negative FNA and in 6 cases from biopsies alone. The tuberculin test (PPD) was positive in all patients with TB adenitis (100%), while an HIV test was negative in all. The sensitivity of FNA cytology alone was 69% but when combined with a skin test it was 85%. It can be concluded that FNA cytology has an important role in the evaluation of TB adenitis, as a non-invasive alternative to excisional biopsy. After 12 months from the start of a 6-month course of combined antituberculous treatment, 32 patients were cured whereas 3 patients had left the country before completing therapy.
Structural and Functional Changes in the Na+/H+ Exchanger Isoform 1, Induced by Erk1/2 Phosphorylation

The human Na+/H+ exchanger isoform 1 (NHE1) is a plasma membrane transport protein that plays an important role in pH regulation in mammalian cells. Because of the generation of protons by intermediary metabolism as well as the negative membrane potential, protons accumulate within the cytosol. Extracellular signal-regulated kinase (ERK)-mediated regulation of NHE1 is important in several human pathologies including in the myocardium in heart disease, as well as in breast cancer as a trigger for growth and metastasis. NHE1 has a N-terminal, a 500 amino acid membrane domain, and a C-terminal 315 amino acid cytosolic domain. The C-terminal domain regulates the membrane domain and its effects on transport are modified by protein binding and phosphorylation. Here, we discuss the physiological regulation of NHE1 by ERK, with an emphasis on the critical effects on structure and function. ERK binds directly to the cytosolic domain at specific binding domains. ERK also phosphorylates NHE1 directly at multiple sites, which enhance NHE1 activity with subsequent downstream physiological effects. The NHE1 cytosolic regulatory tail possesses both ordered and disordered regions, and the disordered regions are stabilized by ERK-mediated phosphorylation at a phosphorylation motif. Overall, ERK pathway mediated phosphorylation modulates the NHE1 tail, and affects the activity, structure, and function of this membrane protein.
Non‐coding RNA MFI2‐AS1 promotes colorectal cancer cell proliferation, migration and invasion through miR‐574‐5p/MYCBP axis

Long non‐coding RNAs (lncRNAs) and microRNAs (miRNAs) play essential roles in the tumour progression. LncRNAs mostly act as competing endogenous RNAs (ceRNAs) by sponging miRNAs. This study aimed to study the association of a novel lncRNA MFI2‐AS1 with miR‐574‐5p/MYCBP axis in the development of colorectal cancer (CRC).
CORVET, CHEVI and HOPS – multisubunit tethers of the endo-lysosomal system in health and disease

ABSTRACT Multisubunit tethering complexes (MTCs) are multitasking hubs that form a link between membrane fusion, organelle motility and signaling. CORVET, CHEVI and HOPS are MTCs of the endo-lysosomal system. They regulate the major membrane flows required for endocytosis, lysosome biogenesis, autophagy and phagocytosis. In addition, individual subunits control complex-independent transport of specific cargoes and exert functions beyond tethering, such as attachment to microtubules and SNARE activation. Mutations in CHEVI subunits lead to arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome, while defects in CORVET and, particularly, HOPS are associated with neurodegeneration, pigmentation disorders, liver malfunction and various forms of cancer. Diseases and phenotypes, however, vary per affected subunit and a concise overview of MTC protein function and associated human pathologies is currently lacking. Here, we provide an integrated overview on the cellular functions and pathological defects associated with CORVET, CHEVI or HOPS proteins, both with regard to their complexes and as individual subunits. The combination of these data provides novel insights into how mutations in endo-lysosomal proteins lead to human pathologies. Summary: The multitasking tethering complexes CORVET, CHEVI and HOPS are major organizers of the endocytic pathway. This Review combines current knowledge on their roles in membrane trafficking and diseases.
The Benefits and Risks of Iron Supplementation in Pregnancy and Childhood.

Iron deficiency is the most common micronutrient deficiency in the world and disproportionately affects pregnant women and young children. Iron deficiency has negative effects on pregnancy outcomes in women and on immune function and neurodevelopment in children. Iron supplementation programs have been successful in reducing this health burden. However, iron supplementation of iron-sufficient individuals is likely not necessary and may carry health risks for iron-sufficient and potentially some iron-deficient populations. This review considers the physiology of iron as a nutrient and how this physiology informs decision-making about weighing the benefits and risks of iron supplementation in iron-deficient, iron-sufficient, and iron-overloaded pregnant women and children. Expected final online publication date for the Annual Review of Nutrition Volume 39 is August 21, 2019. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Cardiorespiratory Fitness as a Mediator of the Association between Physical Activity and Overweight and Obesity in Adolescent Girls.

Background: Overweight and obesity (OW/OB) continue to be prominent health issues among adolescent girls. However, little is known about the interrelationships between physical activity (PA), cardiorespiratory fitness (CRF), and OW/OB in this population. The objective of this study was to examine whether CRF mediates the relationship between PA and OW/OB in adolescent girls. Methods: Moderate-to-vigorous PA (MVPA), CRF, BMI, and percentage body fat (% BF) were measured in adolescent girls (N = 1519), aged 10-14 years, from 24 urban middle schools located in the Midwestern United States. Structural equation modeling was used to determine whether CRF is a mediator of the association between MVPA and OW/OB (measured as both BMI and % BF). Multigroup analyses were used to determine whether race, puberty, or socioeconomic status moderate the mediation models. Results: The indirect effect of MVPA through CRF on OW/OB was significant for both BMI (p < 0.01) and % BF (p < 0.01), indicating that CRF is a complete mediator between MVPA and OW/OB. Both race and puberty significantly (p < 0.05) moderated the mediation between MVPA and OW/OB. Conclusions: This study demonstrates that CRF is improved by increasing MVPA, and the improvement in CRF results in lower BMI and % BF among adolescent girls.
GATA6-upregulating autophagy promotes TKI resistance in nonsmall cell lung cancer

ABSTRACT Autophagy plays a complicated role in tumorigenesis, and the effects of autophagy in drug resistance have not been fully known. The aim of this study was to evaluate autophagy activity in lung cancer cells derived from different origins and explore the mechanism regulating autophagy in tyrosine kinase inhibitor (TKI) resistance. We found basal level of autophagy had no significant increase in resistant H1650 and H1975 cells compared with sensitive HCC827 and PC9 cells. After erlotinib treatment, the autophagy activity enhanced threefold in H1650 cells but a little in H1975 cells. Inhibiting autophagy with 3-MA increased apoptosis in H1650 rather than H1975 cells. Combined with transmission microscope, results showed PC9 cells tended to be apoptotic and more autophagosomes formed in H1650 cells, which may be correlated with cell viability. GATA6 expression was found markedly elevated in H1650 cells after erlotinib and knocking down GATA6 led to significantly reduced autophagy activity and cell viability. Furthermore, a significant increase of GATA6 and LC3-II expression was observed in insensitive tissues compared with sensitive ones by immunostaining in nonsmall cell lung cancer (NSCLC) patients. With chi-square test, we found GATA6 was positively correlated with LC3-II. The Kaplan-Meier curve analyses further showed patients with high GATA6 had lower overall survival and progression-free survival rates than those with low GATA6 after EGFR-TKI treatment. Our results suggest that GATA6 could enhance autophagy activity contributing to TKI resistance. Targeting GATA6 and autophagy together with TKI may be promising to overcome drug resistance in NSCLC.
Measurements of body surface area and volume in male Japanese White rabbits using a computed tomography scanner: comparison with male New Zealand White rabbits

The body surface area (BSA) of animals has generally been estimated by multiplying the k value by the measured body weight (BW) raised to the power of 2/3 (Meeh’s formula). In mathematical terms, the assumption that the density and body shape of animals are essentially constant means that the BSA is proportional to BW2/3. In this study, we measured the BSA and volume of 50 male Japanese White rabbits (JW) at 10 to 54 weeks of age using a computed tomography scanner, then calculated the k value, density, and sphericity. The variations in these parameters were then analyzed in relation to growth. The obtained results indicated that the k value was negatively correlated to BW, and that this negative correlation was mainly due to the variation in density. Based on the regression analysis, we propose the following linear regression equation for calculating the k value in male JW at 10–54 weeks of age: the k value = 14.602 − 0.959 × BW [kg]. The calculated values ranged from 10.9 to 12.7 (working BW range: 1.98 to 3.81 kg). The k value of male New Zealand White rabbits (NZW) determined in our previous study and that of male JW in the present study were compared. It was revealed that the k value of male JW was larger than that of male NZW. We concluded that different breeds of rabbits express different k values.
SIRT1 Modulates the Sensitivity of Prostate Cancer Cells to Vesicular Stomatitis Virus Oncolysis

The use of nonpathogenic viruses to target and kill cancer cells is a promising strategy in cancer therapy. However, many types of human cancer are resistant to the oncolytic (cancer-killing) effects of virotherapy. In this study, we identify a host cellular protein, SIRT1, that contributes to the sensitivity of prostate cancer cells to infection by a prototypical oncolytic virus. Knockout of SIRT1 activity increases the sensitivity of prostate cancer cells to virus-mediated killing. At the molecular level, SIRT1 is controlled by a small microRNA termed miR-34a. Altogether, SIRT1 and/or miR-34a levels may serve as predictors of response to oncolytic-virus therapy. ABSTRACT Oncolytic virotherapy represents a promising experimental anticancer strategy, based on the use of genetically modified viruses to selectively infect and kill cancer cells. Vesicular stomatitis virus (VSV) is a prototypic oncolytic virus (OV) that induces cancer cell death through activation of the apoptotic pathway, although intrinsic resistance to oncolysis is found in some cell lines and many primary tumors, as a consequence of residual innate immunity to the virus. In the effort to improve OV therapeutic efficacy, we previously demonstrated that different agents, including histone deacetylase inhibitors (HDIs), functioned as reversible chemical switches to dampen the innate antiviral response and improve the susceptibility of resistant cancer cells to VSV infection. In the present study, we demonstrated that the NAD+-dependent histone deacetylase SIRT1 (silent mating type information regulation 2 homolog 1) plays a key role in the permissivity of prostate cancer PC-3 cells to VSVΔM51 replication and oncolysis. HDI-mediated enhancement of VSVΔM51 infection and cancer cell killing directly correlated with a decrease of SIRT1 expression. Furthermore, pharmacological inhibition as well as silencing of SIRT1 by small interfering RNA (siRNA) was sufficient to sensitize PC-3 cells to VSVΔM51 infection, resulting in augmentation of virus replication and spread. Mechanistically, HDIs such as suberoylanilide hydroxamic acid (SAHA; Vorinostat) and resminostat upregulated the microRNA miR-34a that regulated the level of SIRT1. Taken together, our findings identify SIRT1 as a viral restriction factor that limits VSVΔM51 infection and oncolysis in prostate cancer cells. IMPORTANCE The use of nonpathogenic viruses to target and kill cancer cells is a promising strategy in cancer therapy. However, many types of human cancer are resistant to the oncolytic (cancer-killing) effects of virotherapy. In this study, we identify a host cellular protein, SIRT1, that contributes to the sensitivity of prostate cancer cells to infection by a prototypical oncolytic virus. Knockout of SIRT1 activity increases the sensitivity of prostate cancer cells to virus-mediated killing. At the molecular level, SIRT1 is controlled by a small microRNA termed miR-34a. Altogether, SIRT1 and/or miR-34a levels may serve as predictors of response to oncolytic-virus therapy.
Association between non-alcoholic fatty liver disease and colorectal cancer

ABSTRACT Introduction: Colorectal cancer (CRC) is a common malignancy, ranking fourth among the causes of cancer-related deaths globally. Its incidence has increased in recent decades, and now more than one million CRC patients are diagnosed and thousands die annually. The 5-year survival rate varies with the stage at diagnosis, are approximately 90% in the early stages of disease, and less than 10% in advanced disease. Non-alcoholic fatty liver disease (NAFLD), which is a major cause of chronic liver disease, and characterized by the accumulation of fat in hepatocytes, has also emerged as a risk factor for CRC, and to be related with the development of colorectal polyps. Areas covered: The purpose of this current review is to summarize the main findings of studies that have investigated the role of NAFLD in development of CRC. Expert opinion: Various molecular pathways are altered during the development of NAFLD, which are also important in CRC tumorigenesis. There is growing body of evidence showing the potential role of activation of pro-inflammatory, disruption of anti-inflammatory pathways, increasing the activity of pathways involved in cell proliferation/survival. Thus targeting these dysregulated pathways via novel inhibitors can be a potential therapy for CRC prevention in cases with NAFLD.
Invisibility Is Not Invincibility: The Impact of Intimate Partner Violence on Gay, Bisexual, and Straight Men’s Mental Health

Intimate partner violence (IPV) is a critical public health problem. However, there is limited research conducted on and about men who are survivors. This project extends previous research by examining the post-traumatic impact of diverse forms of IPV (sexual, physical, emotional, control, and stalking) on the internalized and externalized mental health of gay, bisexual, and straight men. Using data from the National Intimate Partner and Sexual Violence Survey (2011; N = 18,957), we find that all men are equally likely to report emotional victimization and controlling tactics (with between 50% and 70% doing so), while bisexual men are significantly more likely to report physical and sexual violence and gay men are significantly more likely to report intimate stalking. Due to these experiences, gay men are significantly more likely to report missing school or work, but bisexual men are significantly more likely to rate their current overall mental health as poor. Around 10% of all men, regardless of sexual orientation, report post-traumatic stress disorder symptomology and 30% of all men report difficulty sleeping. This research suggests that sexual orientation is a critical area of focus in the study of violence and mental health for men and that we can no longer ignore the voices and needs of men survivors: Invisibility is not invincibility.
Barriers and facilitators to health care professionals discussing child weight with parents: A meta‐synthesis of qualitative studies

Introduction Childhood obesity is one of the most serious global public health challenges. However, obesity and its consequences are largely preventable. As parents play an important role in their children's weight‐related behaviours, good communication between parents and health care professionals (HCPs) is essential. This systematic review provides a meta‐synthesis of qualitative studies exploring the barriers and facilitators experienced by HCPs when discussing child weight with parents. Methods Searches were conducted using the following databases: MEDLINE (OVID), Psych INFO (OVID), EMBASE (OVID), Web of Knowledge and CINAHL. Thirteen full‐text qualitative studies published in English language journals since 1985 were included. Included studies collected data from HCPs (e.g., nurses, doctors, dieticians, psychologists, and clinical managers) concerning their experiences of discussing child weight‐related issues with parents. An inductive thematic analysis was employed to synthesize findings. Findings Emerging subthemes were categorized using a socio‐ecological framework into intra/interpersonal factors, organizational factors, and societal factors. Perceived barriers and facilitators most commonly related to intra/interpersonal level factors, that is, relating to staff factors, parental factors, or professional–parent interactions. HCPs also attributed a number of barriers, but not facilitators, at the organizational and societal levels. Conclusion The findings of this review may help to inform the development of future weight‐related communication interventions. Whilst intra/interpersonal interventions may go some way to improving health care practice, it is crucial that all stakeholders consider the wider organizational and societal context in which these interactions take place. Statement of contribution What is already known on the subject? Childhood obesity is one of the United Kingdom's most serious current public health challenges. Health care professionals are in a prime position to identify child weight issues during routine consultations. However, they often feel unable or unequipped to raise the topic and provide information on child weight management. What does this study add? To our knowledge, this is the first review to synthesize barriers and facilitators to discussing child weight. This review interprets key barriers and facilitators in the context of the socio‐ecological model. Supports the development of interventions matched to the appropriate level of the socio‐economic model.
Preventive Effects of the Marine Microalga Phaeodactylum tricornutum, Used as a Food Supplement, on Risk Factors Associated with Metabolic Syndrome in Wistar Rats

Long-chain polyunsaturated fatty acids, n-3 series (n-3 LC-PUFA), are known for their preventive effects against cardiovascular disease. In an unfavourable economic and environmental context of fish oil production, marine microalgae could be an alternative source of n-3 LC-PUFA and are of interest for human nutrition. The aim of this study was to evaluate the effects of P. tricornutum, a microalga rich in eicosapentaenoic acid and used as a food supplement, on the metabolic disorders associated with metabolic syndrome and obesity development. Three male Wistar rat groups (n = 6) were submitted for eight weeks to a standard diet or high-fat diet (HF) with 10% fructose in drinking water, supplemented or not with 12% of P. tricornutum (HF-Phaeo). Supplementation led to n-3 LC-PUFA enrichment of lipids in the liver, plasma and erythrocytes. Plasma transaminases showed no difference between the HF and HF-Phaeo groups. Body weight, fat mass, inflammatory markers and insulinemia decreased in HF-Phaeo rats versus the HF group. Plasma total cholesterol, triacylglycerols and leptine diminished in HF-Phaeo rats, while HDL-cholesterol increased. In conclusion, this study highlights the beneficial effects of P. tricornutum in reducing the metabolic disorders associated with metabolic syndrome.
Hypervirulent Klebsiella pneumoniae

Hypervirulent K. pneumoniae (hvKp) is an evolving pathotype that is more virulent than classical K. pneumoniae (cKp). hvKp usually infects individuals from the community, who are often healthy. SUMMARY Hypervirulent K. pneumoniae (hvKp) is an evolving pathotype that is more virulent than classical K. pneumoniae (cKp). hvKp usually infects individuals from the community, who are often healthy. Infections are more common in the Asian Pacific Rim but are occurring globally. hvKp infection frequently presents at multiple sites or subsequently metastatically spreads, often requiring source control. hvKp has an increased ability to cause central nervous system infection and endophthalmitis, which require rapid recognition and site-specific treatment. The genetic factors that confer hvKp’s hypervirulent phenotype are present on a large virulence plasmid and perhaps integrative conjugal elements. Increased capsule production and aerobactin production are established hvKp-specific virulence factors. Similar to cKp, hvKp strains are becoming increasingly resistant to antimicrobials via acquisition of mobile elements carrying resistance determinants, and new hvKp strains emerge when extensively drug-resistant cKp strains acquire hvKp-specific virulence determinants, resulting in nosocomial infection. Presently, clinical laboratories are unable to differentiate cKp from hvKp, but recently, several biomarkers and quantitative siderophore production have been shown to accurately predict hvKp strains, which could lead to the development of a diagnostic test for use by clinical laboratories for optimal patient care and for use in epidemiologic surveillance and research studies.