Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of CD31 receptor in CD4+ and CD8+ T-cell subsets in children with primary hypertension is associated with hypertension severity and hypertensive target organ damage

Background: Primary hypertension is associated with still poorly known T-cell dependent immunity defects that participate in the disease development. However, the relationship between peripheral T-cell subset distribution and disease severity in humans is not known. The aim of the study was to find out if target organ damage in adolescents with primary hypertension is associated with thymus-dependent lymphocytes renewal reflected by changes in the T-cell subset phenotype characteristics. Methods: Using seven-color flow cytometry technique, we assessed CD31, CCR7 and CD28 receptors expression in CD45RA and CD45RO bearing peripheral CD4+ and CD8+ T-cell subsets. The study included 32 hypertensive children/adolescents and 35 sex-matched and age-matched controls. Results: Children with primary hypertension had slightly increased CD4+ T-cell pool but decreased population of CD31 expressing CD4+ T-cell subsets (recent thymic emigrants). Frequency of the CD4+ and CD4+/CD45RA+ T cells lacking CD31 correlated positively with the hypertensive organ damage markers (pulse wave velocity, central blood pressure, left ventricular mass index). Left ventricular hypertrophy was associated with decreased CD4/CD45RA:CD4/CD45RO ratio, loss of the CD31 receptor in the CD4+ and CD8+ T-cell subsets and increased population of effector/memory T cells bearing CD8+/CD28− and CD8+/CD45RA+/CCR7− phenotype. Regression analysis revealed that these associations were independent of age, sex, and BMI. Conclusion: The results suggest that subclinical arterial injury and left ventricular hypertrophy in adolescents with primary hypertension is associated with declined thymic function and increased pool of T cells bearing effector/memory phenotype.
COBIT 5 and Enterprise Governance of Information Technology: Building Blocks and Research Opportunities

ABSTRACT: COBIT, currently in its fifth edition, is a good-practice framework for the enterprise governance of IT. There is limited academic research that either analyzes COBIT or leverages COBIT as an instrument in executing research programs. Through linking core elements and principles of COBIT to insights from IT-related and general management literature, this paper explores the use of COBIT in future research activities. This paper positions COBIT as a framework for enterprise governance of IT. The major directions and core principles of the framework are described. Connections are made of these directions and principles to the relevant literature. Research questions for future research around enterprise governance of IT and COBIT 5 are proposed and discussed.
Caregiver experience, health-related quality of life and life satisfaction among informal caregivers to patients with amyotrophic lateral sclerosis: A cross-sectional study.

AIMS AND OBJECTIVES This study set out to describe caregiver experience, health-related quality of life and life satisfaction among informal caregivers to patients with amyotrophic lateral sclerosis and to explore factors associated with caregivers' health-related quality of life and life satisfaction. BACKGROUND Knowledge about factors related to caregivers' health-related quality of life and life satisfaction is important for identification of those at risk for ill health and for development of support and care. DESIGN A cross-sectional study. METHODS Forty-nine informal caregivers and 49 patients were included. Standardised and study-specific questionnaires were used for data collection on caregiver experience (Caregiver Reaction Assessment), health-related quality of life (EuroQol Visual Analogue Scale, SF-36), life satisfaction (Life Satisfaction Checklist) and caregiver- and patient-related factors. Associations were explored by regression analyses. RESULTS Both positive and negative caregiver experience were reported, and health-related quality of life and life satisfaction were below national reference values. Positive experience was associated with better and negative with worse mental health-related quality of life. Factors related to informal caregivers (sex, age, living conditions) and patients (anxiety and/or depression) were related to caregivers' health-related quality and life satisfaction. CONCLUSION The results indicate the need to consider the individual caregiver's experience when planning services, care and support. It is important to adopt person-centred care, not only for patients but also for their informal caregivers, as factors related to both parties were associated with the informal caregivers' health-related quality of life and life satisfaction. RELEVANCE TO CLINICAL PRACTICE Our study suggests that promoting positive experience and providing services and support to reduce negative aspects of caregiving might be important strategies for healthcare personnel to improve informal caregivers' health.
HSV as A Platform for the Generation of Retargeted, Armed, and Reporter-Expressing Oncolytic Viruses

Previously, we engineered oncolytic herpes simplex viruses (o-HSVs) retargeted to the HER2 (epidermal growth factor receptor 2) tumor cell specific receptor by the insertion of a single chain antibody (scFv) to HER2 in gD, gH, or gB. Here, the insertion of scFvs to three additional cancer targets—EGFR (epidermal growth factor receptor), EGFRvIII, and PSMA (prostate specific membrane antigen)—in gD Δ6–38 enabled the generation of specifically retargeted o-HSVs. Viable recombinants resulted from the insertion of an scFv in place of aa 6–38, but not in place of aa 61–218. Hence, only the gD N-terminus accepted all tested scFv inserts. Additionally, the insertion of mIL12 in the US1-US2 intergenic region of the HER2- or EGFRvIII-retargeted o-HSVs, and the further insertion of Gaussia Luciferase, gave rise to viable recombinants capable of secreting the cytokine and the reporter. Lastly, we engineered two known mutations in gB; they increased the ability of an HER2-retargeted recombinant to spread among murine cells. Altogether, current data show that the o-HSV carrying the aa 6–38 deletion in gD serves as a platform for the specific retargeting of o-HSV tropism to a number of human cancer targets, and the retargeted o-HSVs serve as simultaneous vectors for two molecules.
Preventive Effects of Dairy Products on Dementia and the Underlying Mechanisms

Alongside the rapid population aging occurring worldwide, the prevention of age-related memory decline and dementia has become a high priority. Dairy products have many physiological effects owing to their contents of lactic acid bacteria and the fatty acids and peptides generated during their fermentation. In particular, several recent studies have elucidated the effects of fermented dairy products on cognitive function. Epidemiological and clinical evidence has indicated that fermented dairy products have preventive effects against dementia, including Alzheimer’s disease. Recent preclinical studies have identified individual molecules generated during fermentation that are responsible for those preventive effects. Oleamide and dehydroergosterol have been identified as the agents responsible for reducing microglial inflammatory responses and neurotoxicity. In this review, the protective effects of fermented dairy products and their components on cognitive function, the mechanisms underlying those effects, and the prospects for their future clinical development will be discussed.
Are cortisol concentrations in human breast milk associated with infant crying?

Abstract The present longitudinal study is the first to investigate the association between human breast milk cortisol and infant crying over the first three months of life. Higher concentrations of breast milk cortisol were expected to be differentially associated with fussing and crying in boys and girls. At 2, 6, and 12 weeks of infant age, mothers (N = 70) collected a morning sample of their milk and kept a 3‐day diary to measure infant fussing and crying. Cortisol was extracted and quantified from milk samples. Results showed that breast milk cortisol concentrations increased from 2 weeks through 12 weeks of infant age. Milk cortisol was unrelated to the total duration, frequency, and bout length of infant fussing and crying for both boys and girls. Directions for future research aiming to extend our knowledge on the biology of milk cortisol in relation to infant behavior and development are discussed.
Optomotor steering and flight control requires a specific sub-section of the compound eye in the hawkmoth, Manduca sexta

ABSTRACT While tracking odor plumes, male hawkmoths use optic flow cues to stabilize their flight movements with respect to their environment. We studied the responses of freely flying moths tracking odor plumes in a laboratory wind tunnel and tethered moths in an optomotor flight simulator to determine the locations on the compound eye on which critical optic flow cues are detected. In these behavioral experiments, we occluded specific regions of the compound eye and systematically examined the moths' behavior for specific deficits in optic flow processing. Freely flying moths with the dorsal half of the compound eye painted were unable to maintain stable flight and track the wind-borne odor plume. However, the plume tracking performance of moths with the ventral half of their compound eyes painted was the same as unpainted controls. In a matched set of experiments, we presented tethered moths with moving vertically oriented sinusoidal gratings and found that individuals with their eyes unpainted, ventrally painted and medially painted all responded by attempting optomotor-driven turns in the same proportion. In contrast, individuals with their compound eyes dorsally painted, laterally painted and completely painted showed no optomotor turning response. We decreased the contrast of the visual stimulus and found that this relationship was consistent down to a contrast level of 2.5%. We conclude that visual input from the dorso-lateral region of the moth's visual world is critical for successful maintenance of flight stability and that this species' visual environment must meet or exceed a contrast ratio of 2.5% to support visual flight control. Summary: The dorso-lateral quadrant of the Manduca sexta eye is required for optomotor responses and the dorsal half of the compound eye is necessary for free-flight behavior.
Synergistic inactivation of AXL: a (cross)road to cure ovarian cancer?

Inhibition of the receptor tyrosine kinase AXL, a key molecular driver of ovarian cancer, has recently been highlighted as promising therapeutic strategy. In this issue of EMBO Reports, Antony et al have identified a novel mechanism of inhibition of AXL, wherein the GPI‐anchored tumour suppressor OPCML sequesters AXL into specialised plasma membrane domains where the phosphatase PTPRG is located, therefore facilitating AXL dephosphorylation. This attenuation of AXL signalling has translational implications for the design of synergistic therapies, to target the kinase for this aggressive malignancy.
Myths and realities about alcohol and smoking in chronic pancreatitis

Purpose of review Alcohol and smoking play an important role in pancreatitis. The present review will address the myths and evidences about alcohol and smoking with pancreatitis to help improve the approach of healthcare professionals when managing of these patients. Recent findings There is a growing recognition that chronic pancreatitis is a multifactorial disease. Eliciting an accurate history of alcohol consumption and smoking from patients, and if necessary, family members, can help determine their contribution to the patient's disease. In the absence of a convincing history, physicians should be open to consideration of other etiologies. The amount and duration of alcohol consumption is the most important determinant in increasing pancreatitis risk. Alcohol sensitizes the pancreas to other insults or injury and promotes disease progression. Smoking is an independent risk factor or chronic pancreatitis and has synergistic pathogenic effects with alcohol. The natural history of chronic pancreatitis is highly variable. A patient with alcoholic pancreatitis can have symptoms, recurrences or exacerbations from disease-related complications or nonpancreatic causes. Novel strategies are needed to enable patients quit smoking. Summary Obtaining accurate history, appropriate evaluation and management can help to achieve meaningful improvement in symptoms in patients with chronic pancreatitis. Abstinence from alcohol and smoking cessation, when applicable, should be recommended in all patients to prevent disease recurrences and progression.
Progress towards obtaining an HIV cure: slow but sure.

DOI:10.1097/COH.0000000000000492 Over the past decade, there has been rapid evolution and expansion in scientific and community interest in HIV curative strategies. The initial report of the cure of Timothy Brown (The Berlin Patient) following CCR5 D32/D32 stem-cell transplantation in 2009 [1] was a major catalyst in bringing together various stake-holders, including government funding agencies, private foundations, community and advocacy groups, ethicists, regulatory agencies, pharmaceutical companies, scientists and clinicians, to work towards the goal of achieving a sterilizing cure or durable control of HIV after stopping antiretroviral therapy (ART). Dedicated funding opportunities provided support for those working towards these challenging goals, leading to an exponential increase in the number of scientific articles, public articles and media coverage. The status of these efforts was extensively summarized by the International AIDS Society global strategy towards an HIV cure in 2016 [2]. Although additional cases such as Timothy Brown have yet to materialize, the HIV cure field has rapidly expanded to include work on discovering biomarkers of persistent HIV infection, development and implementation of immunological approaches to controlling HIV following ART cessation, cell and gene therapy approaches, early initiation of ART, latency promoting or reversing strategies and development of novel assays to locate, quantify and characterize persistent HIV reservoirs. Although working towards an HIV cure has been met with many scientific and practical challenges, there has been recent, palpable progress. For example, durable control of simian immunodeficiency virus (SIV) has recently been reported in nonhuman primate studies including the use of therapeutic HIV vaccine combined with Toll-like receptor agonists and mAbs directed towards viral envelope proteins or a4b7 integrin, to name just a few [3–5]. Additional cases of prolonged HIV remission prior to viral recrudescence, sometimes lasting many months, have been reported in small, proofof-concept human studies, although none have lead to unequivocal, sustained HIV cure [6,7]. Work on other strategies has also accelerated, including the search for biomarkers of residual HIV-infected cells
Things Are Changing so Fast

Background and Objectives Multimodal interventions are increasingly targeting multiple cognitive decline risk factors. However, technology remains mostly adjunctive, largely prioritizes age relevancy over cultural relevancy, and often targets individual health without lasting, community-wide deliverables. Meanwhile, African Americans remain overburdened by cognitive risk factors yet underrepresented in cognitive health and technology studies. The Sharing History through Active Reminiscence and Photo-imagery (SHARP) program increases physical, social, and cognitive activity within a culturally meaningful context that produces community deliverables-an oral history archive and cognitive health education. Design and Methods The SHARP application was tested with 19 African Americans ≥55 years, aiming for an easy, integrative, and culturally meaningful experience. The application guided triads in walks 3 times weekly for 6 months in Portland, Oregon's historically Black neighborhoods; local historical images prompted recorded conversational reminiscence. Focus groups evaluated factors influencing technology acceptance-attitudes about technology, usefulness, usability, and relevance to integrating program goals. Thematic analysis guided qualitative interpretation. Results Technology acceptance was influenced by group learning, paper-copy replicas for reluctant users, ease of navigation, usefulness for integrating and engaging in health behaviors, relevance to integrating individual benefit and the community priority of preserving history amidst gentrification, and flexibility in how the community uses deliverables. Perceived community benefits sustained acceptance despite intermittent technology failure. Discussion and Implications We offer applicable considerations for brain health technology design, implementation, and deliverables that integrate modalities, age, and cultural relevance, and individual and community benefit for more meaningful, and thus more motivated community engagement.
APOL1 risk variants cause podocytes injury through enhancing endoplasmic reticulum stress

Two coding sequence variants (G1 and G2) of Apolipoprotein L1 (APOL1) gene have been implicated as a higher risk factor for chronic kidney diseases (CKD) in African Americans when compared with European Americans. Previous studies have suggested that the APOL1 G1 and G2 variant proteins are more toxic to kidney cells than the wild-type APOL1 G0, but the underlying mechanisms are poorly understood. To determine whether endoplasmic reticulum (ER) stress contributes to podocyte toxicity, we generated human podocytes (HPs) that stably overexpressed APOL1 G0, G1, or G2 (Vec/HPs, G0/HPs, G1/HPs, and G2/HPs). Propidium iodide staining showed that HP overexpressing the APOL1 G1 or G2 variant exhibited a higher rate of necrosis when compared with those overexpressing the wild-type G0 counterpart. Consistently, the expression levels of nephrin and podocin proteins were significantly decreased in the G1- or G2-overexpressing cells despite the maintenance of their mRNA expressions levels. In contrast, the expression of the 78-kDa glucose-regulated protein ((GRP78), also known as the binding Ig protein, BiP) and the phosphorylation of the eukaryotic translation initiation factor 1 (eIF1) were significantly elevated in the G1/HPs and G2/HPs, suggesting a possible occurrence of ER stress in these cells. Furthermore, ER stress inhibitors not only restored nephrin protein expression, but also provided protection against necrosis in G1/HPs and G2/HPs, suggesting that APOL1 risk variants cause podocyte injury partly through enhancing ER stress.
The Outcomes of Broadcasting Self-Disclosure Using New Communication Technologies: Responses to Disclosure Vary Across One’s Social Network

Several new communication technologies have made it relatively easy for individuals to broadcast a single self-disclosure directly to almost everyone with whom they share a relationship—ranging from close friends to little-known acquaintances. Drawing from research on self-disclosure and the negativity effect, two studies were conducted to test the notion that the interpersonal and relational outcomes of broadcasting positive and negative self-disclosures are not uniform. The results of the cross-sectional survey offer evidence that the outcomes of positive and negative broadcasted disclosures vary depending on the receiver’s relationship with the discloser. The results from the experiment largely support the negativity effect explanation for differences in the outcomes of broadcasted disclosures. Relative to positive disclosures, negative broadcasted self-disclosures have a significantly greater impact on acquaintances than on friends’ perceptions of the discloser and their relationship.
Discovery of UDP-Glycosyltransferases and BAHD-Acyltransferases Involved in the Biosynthesis of the Antidiabetic Plant Metabolite Montbretin A[OPEN]

Glycosyltransferases and acyltransferases in corms of the ornamental plant montbretia are involved in a complex flavonoid biosynthetic system relevant to human health. Plant specialized metabolism serves as a rich resource of biologically active molecules for drug discovery. The acylated flavonol glycoside montbretin A (MbA) and its precursor myricetin 3-O-(6’-O-caffeoyl)-glucosyl rhamnoside (mini-MbA) are potent inhibitors of human pancreatic α-amylase and are being developed as drug candidates to treat type-2 diabetes. MbA occurs in corms of the ornamental plant montbretia (Crocosmia x crocosmiiflora), but a system for large-scale MbA production is currently unavailable. Biosynthesis of MbA from the flavonol myricetin and MbA accumulation occur during early stages of corm development. We established myricetin 3-O-rhamnoside (MR), myricetin 3-O-glucosyl rhamnoside (MRG), and mini-MbA as the first three intermediates of MbA biosynthesis. Contrasting the transcriptomes of young and old corms revealed differentially expressed UDP-sugar-dependent glycosyltransferases (UGTs) and BAHD-acyltransferases (BAHD-ATs). UGT77B2 and UGT709G2 catalyze the consecutive glycosylation of myricetin to produce MR and of MR to give MRG, respectively. In addition, two BAHD-ATs, CcAT1 and CcAT2, catalyze the acylation of MRG to complete the formation of mini-MbA. Transcript profiles of UGT77B2, UGT709G2, CcAT1, and CcAT2 during corm development matched the metabolite profile of MbA accumulation. Expression of these enzymes in wild tobacco (Nicotiana benthamiana) resulted in the formation of a surrogate mini-MbA, validating the potential for metabolic engineering of mini-MbA in a heterologous plant system.
CALD Assist—Nursing: Improving communication in the absence of interpreters

AIMS AND OBJECTIVES To develop a communication app to support nursing staff during the provision of standard care of patients from non-English-speaking backgrounds (NESBs), when an interpreter is not available. This paper reports on the user needs analysis phase that informed the development, content and functionality of the app. BACKGROUND In 2014 we developed CALD Assist, a communication app to support patient interactions with allied health clinicians when interpreters are not present. It includes 95 commonly used phrases professionally interpreted into 10 languages and grouped by discipline. This work expands upon our previous app to meet the needs of the nursing workforce. DESIGN Qualitative through focus groups, observations and interviews, with a quantitative component from observational data and staff surveys. METHODS Four focus groups with hospital staff, ten interviews with patients from NESBs and 85 observation sessions of everyday patient-staff interactions followed by staff surveys (n = 85) were held between January and June 2017. RESULTS Baseline data prior to app development revealed that staff confidence of the patients' level of understanding and the success of the interaction were significantly greater for English-speaking (ES) patients, than for non-English-speaking patients. A total of 143 phrases were identified and subdivided into 16 categories for inclusion in the new app. CONCLUSION Staff participants highlighted that patients from NESBs are a challenging patient group to interact with. Patient and staff participants identified a range of areas where the nursing app could benefit, including pain management, mobility, hygiene and nutrition. RELEVANCE TO CLINICAL PRACTICE The proposed app can be used to reduce variances in practice and provide a timely and positive patient experience for patients from NESBs who are unable to communicate in English during hospital admissions.