Miracle-dz/UniFAR-FTUs huggingface dataset:
STAT6 degradation and ubiquitylated TRIML2 are essential for activation of human oncogenic herpesvirus

Aberrations in STAT6-mediated signaling are linked to the development of multiple cancer types. Increasing evidence has shown that activation of human oncogenic herpesvirus lytic replication is crucial for viral tumorigenesis. However, the role of STAT6 in herpesvirus lytic replication remains elusive. Here, by using Kaposi’s sarcoma-associated herpesvirus (KSHV) as a model, we revealed that RTA, the master regulator of lytic replication, interacts with STAT6 and promotes lysine 48 (K48) and K63-linked ubiquitylation of STAT6 for degradation via the proteasome and lysosome systems. Moreover, degradation of STAT6 is dramatically associated with the increased ubiquitylated form of tripartite motif family like 2 (TRIML2, a tumor suppressor) for prolonged cell survival and virion production, which is also commonly observed in lytic activation of Epstein-Barr virus, herpes simplex virus 1 and cytomegalovirus. These results suggest that degradation of STAT6 is important for the lytic activation of KSHV and as such, may be an attractive therapeutic target.
Low magnesium diet aggravates phosphate-induced kidney injury.

Background Magnesium is known to protect against phosphate-induced tubular cell injuries in vitro. We investigated in vivo effects of magnesium on kidney injuries and phosphate metabolism in mice exposed to a high phosphate diet. Methods Heminephrectomized mice were maintained on a high phosphate/normal magnesium diet or a high phosphate/low magnesium diet for 6 weeks. We compared renal histology, phosphaturic hormones and renal α-Klotho expression between the two diet groups. Results High phosphate diet-induced tubular injuries and interstitial fibrosis were remarkably aggravated by the low-magnesium diet. At 1 week after high phosphate feeding when serum creatinine levels were similar between the two groups, the low magnesium diet suppressed not only fecal phosphate excretion but also urinary phosphate excretion, resulting in increased serum phosphate levels. Parathyroid hormone (PTH) levels were not appropriately elevated in the low magnesium diet group despite lower 1,25-dihydroxyvitamin D and serum calcium levels compared with the normal magnesium diet group. Although fibroblast growth factor 23 (FGF23) levels were lower in the low magnesium diet group, calcitriol-induced upregulation of FGF23 could not restore the impaired urinary phosphate excretion. The low magnesium diet markedly downregulated α-Klotho expression in the kidney. This downregulation of α-Klotho occurred even when mice were fed the low phosphate diet. Conclusions A low magnesium diet aggravated high phosphate diet-induced kidney injuries. Impaired PTH secretion and downregulation of renal α-Klotho were likely to be involved in the blunted urinary phosphate excretion by the low magnesium diet. Increasing dietary magnesium may be useful to attenuate phosphate-induced kidney injury.
Effectiveness of a brief behavioural intervention to prevent weight gain over the Christmas holiday period: randomised controlled trial

Abstract Objective To test the effectiveness of a brief behavioural intervention to prevent weight gain over the Christmas holiday period. Design Two group, double blinded randomised controlled trial. Setting Recruitment from workplaces, social media platforms, and schools pre-Christmas 2016 and 2017 in Birmingham, UK. Participants 272 adults aged 18 years or more with a body mass index of 20 or more: 136 were randomised to a brief behavioural intervention and 136 to a leaflet on healthy living (comparator). Baseline assessments were conducted in November and December with follow-up assessments in January and February (4-8 weeks after baseline). Interventions The intervention aimed to increase restraint of eating and drinking through regular self weighing and recording of weight and reflection on weight trajectory; providing information on good weight management strategies over the Christmas period; and pictorial information on the physical activity calorie equivalent (PACE) of regularly consumed festive foods and drinks. The goal was to gain no more than 0.5 kg of baseline weight. The comparator group received a leaflet on healthy living. Main outcome measures The primary outcome was weight at follow-up. The primary analysis compared weight at follow-up between the intervention and comparator arms, adjusting for baseline weight and the stratification variable of attendance at a commercial weight loss programme. Secondary outcomes (recorded at follow-up) were: weight gain of 0.5 kg or less, self reported frequency of self weighing (at least twice weekly versus less than twice weekly), percentage body fat, and cognitive restraint of eating, emotional eating, and uncontrolled eating. Results Mean weight change was −0.13 kg (95% confidence interval −0.4 to 0.15) in the intervention group and 0.37 kg (0.12 to 0.62) in the comparator group. The adjusted mean difference in weight (intervention−comparator) was −0.49 kg (95% confidence interval −0.85 to −0.13, P=0.008). The odds ratio for gaining no more than 0.5 kg was non-significant (1.22, 95% confidence interval 0.74 to 2.00, P=0.44). Conclusion A brief behavioural intervention involving regular self weighing, weight management advice, and information about the amount of physical activity required to expend the calories in festive foods and drinks prevented weight gain over the Christmas holiday period. Trial registration ISRCTN Registry ISRCTN15071781.
Alzheimer's disease: nutritional status and cognitive aspects associated with disease severity.

INTRODUCTION Alzheimer's pathology is a neurodegenerative disease characterized by cognitive impairment and functional disability that causesprogressive restrictions in daily activities. The present study associates nutritional status with cognitive and clinical aspects of the elderly withmild, moderate and severe Alzheimer's disease (AD). METHODS data from the Mini Nutritional Assessment (MNA), bioelectrical impedance (BIA), anthropometric measurements, and physical activityindicators were associated with clinical and cognitive aspects of 43 elderly patients with AD. The data were compared to a paired control group (NC) (n = 51) at a significance level of p < 0.05. RESULTS elderly patients with AD presented lower cognitive performance, higher risk of malnutrition (p = 0.001), lower weight (t-test, p = 0.017) and body mass index (BMI) (p = 0.006), and higher sedentarity (Chi-square, p = 0.040) when compared with the NC. The elderly with AD presented significant reduction in lean body mass (LM) and increased fat mass (FM). As dementia progresses, significant impairment of nutritional indicators is observed. Elderly patients with severe AD present lower weight, BMI, MNA scores and increased body fat mass index and fat mass when compared with those with mild/moderate AD. A correlation was observed between better cognitive performance and weight, BMI, calf circumference and triceps skinfold thickness. CONCLUSION elderly patients with AD present high sedentarity, risk of malnutrition, lower weight, BMI and LM, and increased FM. There was progressive impairment of nutritional status and cognition as the disease progressed. There is an association between the nutritional variables and cognitive aspects.
Outcomes of relapsed human papillomavirus‐related oropharyngeal squamous cell carcinoma treated with curative intent

With most centers reporting excellent disease control following transoral surgery for human papillomavirus (HPV)‐related oropharyngeal cancer, data are still lacking regarding management and outcomes in patients who relapse. We describe the treatment outcomes after curative intent therapy for locoregional and distant relapse following transoral surgery for HPV‐related oropharyngeal squamous cell carcinoma (OPSCC).
Functional characterization of the horizontally transferred 4,5‐DOPA extradiol dioxygenase gene in the domestic silkworm, Bombyx mori

4,5‐DOPA dioxygenase (DODA) is a crucial enzyme in the biosynthetic pathway of betalain. Previous studies have shown that DODA is present in plants, fungi and bacteria. Using updated data, here we show that DODA genes (BmDODA) in the domestic silkworm (Bombyx mori) and other lepidopteran insects are most likely to be horizontally transferred from fungi. A synteny analysis indicated that BmDODA1 is orthologous to other lepidopteran DODAs and that BmDODA2 is a paralogous gene. To explore the function of DODA in Lepidoptera, we first examined the expression patterns of BmDODA1. BmDODA1 showed high transcriptional and translational levels in the midgut and head. Then, we exogenously expressed the BmDODA1 gene, detected 4,5‐DOPA ring‐cleaving activity and calculated the kinetic parameters of the recombinant BmDODA1. We found that the transcription levels of BmDODA1 were significantly induced by the pathogens Bacillus bombyseptieus and Escherichia coli. Thus, the horizontal transfer of the BmDODA gene in the silkworm may be involved in dopa metabolism and contribute to antimicrobial activity in this species. Our results provide a documented example of functional horizontal gene transfer (HGT) between fungi and animals and expand our knowledge of HGT amongst eukaryotes.
Changes in spinal stiffness with chronic thoracic pain: Correlation with pain and muscle activity

Objective The objective was to compare thoracic spinal stiffness between healthy participants and participants with chronic thoracic pain and to explore the associations between spinal stiffness, pain and muscle activity. The reliability of spinal stiffness was also evaluated. Material and methods Spinal stiffness was assessed from T5 to T8 using a mechanical device in 25 healthy participants and 50 participants with chronic thoracic pain (symptoms had to be reported within the evaluated region of the back). The spinal levels for which spinal stiffness was measured were standardized (i.e. T5 to T8 for all participants) to minimize between-individual variations due to the evaluation of different spinal levels. The device load and displacement data were used to calculate the global and terminal spinal stiffness coefficients at each spinal level. Immediately after each assessment, participants were asked to rate their pain intensity during the trial, while thoracic muscle activity was recorded during the load application using surface electromyography electrodes (sEMG). Within- and between-day reliability were evaluated using intraclass correlation coefficients (ICC), while the effects of chronic thoracic pain and spinal levels on spinal stiffness and sEMG activity were assessed using mixed model ANOVAs. Correlations between pain intensity, muscle activity and spinal stiffness were also computed. Results ICC values for within- and between-day reliability of spinal stiffness ranged from 0.67 to 0.91 and from 0.60 to 0.94 (except at T5), respectively. A significant decrease in the global (F1,73 = 4.04, p = 0.048) and terminal (F1,73 = 4.93, p = 0.03) spinal stiffness was observed in participants with thoracic pain. sEMG activity was not significantly different between groups and between spinal levels. Pain intensity was only significantly and "moderately" correlated to spinal stiffness coefficients at one spinal level (-0.29≤r≤-0.51), while sEMG activity and spinal stiffness were not significantly correlated. Conclusion The results suggest that spinal stiffness can be reliably assessed using a mechanical device and that this parameter is decreased in participants with chronic thoracic pain. Studies are required to determine the value of instrumented spinal stiffness assessment in the evaluation and management of patients with chronic spine-related pain.
Women’s childbearing location preferences in South Ethiopia: a qualitative study

Abstract Maternal mortality is unacceptably high in developing countries, and maternal health care service utilization is associated with improved maternal outcomes. We shed light on conditions that influence women’s preferences for childbirth location. Based on a qualitative descriptive design, 25 interviews were conducted with women of childbearing age in Southern Ethiopia in 2015. Previous experience of complications was the most common reason for using skilled attendants at the next childbirth. In addition, women’s limited decision-making authority and knowledge, as well as the quality of health care services and infrastructure, influenced childbirth location preferences. Home birth is still the norm, but there is growing interest in using health facilities and skilled attendants.
Novel therapeutic agents for relapsed classical Hodgkin lymphoma

Hodgkin Lymphoma (HL) is a B‐cell lymphoproliferative disorder with an excellent prognosis for the majority of patients who are treated with multi‐agent chemotherapy, with or without radiation. A subset of patient, however, does not respond to therapy or relapses after accomplishing an initial response. Their outcome is poor and new treatment strategies are urgently needed for this patient population. Recent advances in the understanding of the tumour biology of HL and its microenvironment have ushered a new era of targeted‐ and immuno‐therapies with remarkable activity. Most notably, the antibody‐drug conjugate brentuximab‐vedotin, and the immune checkpoint blockers pembrolizumab and nivolumab have recently been approved by the US Food and Drug Administration and have transformed the therapeutic landscape of this disease. Other novel drug compounds are being investigated either as single agents or in combination and hold promise to further the field.
Efficacy and safety of sacubitril/valsartan compared with olmesartan in Asian patients with essential hypertension: A randomized, double‐blind, 8‐week study

This study assessed the efficacy and safety of angiotensin receptor neprilysin inhibitor sacubitril/valsartan vs olmesartan in Asian patients with mild‐to‐moderate hypertension. Patients (N = 1438; mean age, 57.7 years) with mild‐to‐moderate hypertension were randomized to receive once daily administration of sacubitril/valsartan 200 mg (n = 479), sacubitril/valsartan 400 mg (n = 473), or olmesartan 20 mg (n = 486) for 8 weeks. The primary endpoint was reduction in mean sitting systolic blood pressure (msSBP) from baseline with sacubitril/valsartan 200 mg vs olmesartan 20 mg at Week 8. Secondary endpoints included msSBP reduction with sacubitril/valsartan 400 mg, and reductions in clinic and ambulatory BP and pulse pressure (PP) vs olmesartan. In addition, changes in msBP from baseline in the Chinese subpopulation, elderly (≥65 years), and in patients with isolated systolic hypertension (ISH) were assessed. Sacubitril/valsartan 200 mg provided a significantly greater reduction in msSBP than olmesartan 20 mg at Week 8 (between‐treatment difference: −2.33 mm Hg [95% confidence interval (CI) −4.00 to −0.66 mm Hg], P < 0.05 for non‐inferiority and superiority). Greater reductions in msSBP were also observed with sacubitril/valsartan 400 mg vs olmesartan 20 mg (−3.52 [−5.19 to −1.84 mm Hg], P < 0.001 for superiority). Similarly, greater reductions in msBP were observed in the Chinese subpopulation, in elderly patients, and those with ISH. In addition, both doses of sacubitril/valsartan provided significantly greater reductions from baseline in nighttime mean ambulatory BP vs olmesartan. Treatment with sacubitril/valsartan 200 or 400 mg once daily is effective and provided superior BP reduction than olmesartan 20 mg in Asian patients with mild‐to‐moderate hypertension and is generally safe and well tolerated.
Elective neck dissection in metastatic cutaneous squamous cell carcinoma to the parotid gland: A systematic review and meta‐analysis

Current management of metastatic cutaneous squamous cell carcinoma (CSCC) to the parotid is surgical excision and postoperative radiotherapy. In the node‐negative neck, there is debate about the role of elective neck dissection (END), irradiation or observation. This systematic review assesses the prevalence of occult cervical disease and the evidence for END. A literature search was performed using Medline and Embase. All papers describing management of the neck in metastatic CSCC to the parotid were assessed for inclusion. Eighty‐nine papers were identified and 17 met inclusion criteria. A total of 874 ENDs were performed in 874 patients with metastatic CSCC to the parotid with no clinically evident cervical disease. The overall prevalence of occult disease in a random effects model was 22.5% (95% confidence intervals 18.9‐26.0). The prevalence of occult cervical disease in metastatic CSCC to the parotid is high. END is recommended in this patient group.
Manganese-Enhanced Magnetic Resonance Imaging: Overview and Central Nervous System Applications With a Focus on Neurodegeneration

Manganese-enhanced magnetic resonance imaging (MEMRI) rose to prominence in the 1990s as a sensitive approach to high contrast imaging. Following the discovery of manganese conductance through calcium-permeable channels, MEMRI applications expanded to include functional imaging in the central nervous system (CNS) and other body systems. MEMRI has since been employed in the investigation of physiology in many animal models and in humans. Here, we review historical perspectives that follow the evolution of applied MRI research into MEMRI with particular focus on its potential toxicity. Furthermore, we discuss the more current in vivo investigative uses of MEMRI in CNS investigations and the brief but decorated clinical usage of chelated manganese compound mangafodipir in humans.
Burden of Children Hospitalized With Pertussis in Canada in the Acellular Pertussis Vaccine Era, 1999–2015

Abstract Background Recent increases in pertussis morbidity and mortality rates among young infants have led to a recommendation in some countries for vaccination against pertussis during pregnancy. Having data on the burden of pediatric pertussis in a large population over time is important for establishing the true burden of disease in the acellular pertussis (aP) vaccine era. Here, we describe age-specific epidemiology and morbidity and mortality rates in children hospitalized with pertussis over 17 years across Canada in the aP vaccine era. Methods Patients aged ≤16 years who were admitted to 1 of 12 pediatric tertiary-care hospitals across Canada between 1999 and 2015 with confirmed (laboratory-confirmed or epidemiologically linked) or probable (clinically diagnosed) pertussis were included. Results Overall, 1402 patients with pertussis were included. Infants aged <2 months had the highest mean annual incidences of pertussis hospitalization and intensive care unit (ICU) admission (116.40 [95% confidence interval (CI), 85.32–147.49] and 33.48 [95% CI, 26.35–40.62] per 100 000 population, respectively). The overall proportion of children who required ICU admission was 25.46%, and the proportion was highest in infants aged <2 months (37.90%). Over the span of this study, 21 deaths occurred. Age of <16 weeks, prematurity, encephalopathy, and a confirmed pertussis diagnosis were independent risk factors for ICU admission. Age of <4 weeks, prematurity, and female sex were independent risk factors for death. Conclusions In the aP vaccine era, endemic pertussis still contributes considerably to childhood morbidity and death, particularly in infants aged <2 months. Vaccination against pertussis during pregnancy has the potential to reduce this disease burden.
Snakehead Consumption Enhances Wound Healing? From Tradition to Modern Clinical Practice: A Prospective Randomized Controlled Trial

Background Snakehead fish (Channa striatus) is a fresh water fish indigenous to many Asia countries and believed to have medical value. Studies showed that it contains all the essential amino acids and fatty acids able to accelerate wound healing and it has antinociceptive effect. However, little human study has been done to assess the effectiveness of Channa striatus in wound healing. A prospective RCT has been conducted on the effect of Channa striatus spray versus placebo on clean wound to assess its pain control effect and cosmetic outcome. Methodology One hundred and two patients (102) underwent clean elective surgery; postoperatively they were randomized into two group. One group received Channa striatus extract spray (n=51) another group received placebo (n=51) on daily basis for 2 weeks. They were followed up on 2nd, 4th, and 6th weeks. Pain control effect was assessed based on Visual Analog Pain Score (VAPS) and cosmetic outcome based on Visual Analog Cosmetic Scale (VACS), Wound Evaluation Scale (WES), and Vancouver Scar Scale (VSS). Result The patient treated with Channa striatus spray displayed a better outcome in terms of pain control compared to placebo. During analysis using repeated measure ANOVA, there was significant difference of patient's pain score based on VAPS between Channa striatus spray and placebo (F-stat (df) = 4.80 (2), p-value = 0.010). For cosmetic outcome it showed a better result in Channa striatus spray group for all the 3-scoring system, VACS, (F-stat (df) = 2.68 (2) , p-value <0.001), WES (F-stat (df) = 3.09 (2), p-value = 0.048), and VSS (F-stat (df) = 1.72 (2) , p-value = 0.011). Conclusion Our study suggest that application of Channa striatus extract spray on clean wound has shown a significant better pain score result and cosmetic outcome on week 2, week 4, and week 6 comparatively with placebo.
Nurses' Perspective on Caring for Women Experiencing Perinatal Loss

Purpose: The purpose of this study was to describe the experience of caring for women with a perinatal loss from the perspective of the nurse and to determine the extent to which the response to perinatal loss reflects a process. Study Design and Methods: A purposive study was conducted with nine labor and birth nurses with experience in caring for women with a perinatal loss. The nurses were from two acute care hospitals within one healthcare system in Southeastern Massachusetts. A qualitative descriptive design with in-depth interviewing based on Rubin and Rubin (2012) was used to gather and analyze data. Results: Several themes depicting nurses' experience were identified: struggling with emotions, carrying on in the moment, being present for the patient, expressing conflict, and taking care of self. A process was identified by nurses describing their response to perinatal loss. The process began with recognition of the loss and progressed through phases including the recognition of their emotional impact, connecting with the mother, dealing with emotions, acting professionally, preparing to return to work, and never forgetting the woman. Clinical Implications: Nurses identified a need for more education and managerial support for excellence in care of women with a perinatal loss. Education to prepare nurses to meet the physical, psychological, and spiritual needs of women is recommended. Debriefing after caring for a woman with a loss was suggested by the nurses. When nurses' needs are met, they are better prepared to care for women experiencing a perinatal loss.