Miracle-dz/UniFAR-FTUs huggingface dataset:
Ustekinumab for Crohn’s disease: a nationwide real-life cohort study from Finland (FINUSTE)

Abstract Background: Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, has been approved for treatment of Crohn’s Disease (CD) since the end of 2016. This nationwide noninterventional, retrospective chart review explored real-life data in patients receiving UST to provide guidance in UST treatment in the era of increasing prevalence of CD. Methods: The study assessed UST treatment patterns such as dosing frequency, concomitant medication and persistence in 48 CD patients commencing UST therapy in 12 Finnish hospitals during 2017. Clinical remission and response rates were explored using a modified Harvey–Bradshaw index (mHBI) and endoscopic response via the simple endoscopic score for Crohn’s disease (SES-CD) as proportions of patients at week 16 and at the end of follow-up. Results: Forty patients (83%) continued UST-treatment at the end of follow-up. At week 16, clinical response and endoscopic healing was observed, where data were available; mHBI decreased from 9 to 3 (p = .0001) and SES-CD from 12 to 3 (p = .009). Clinical benefit was achieved by 83% (19/23) at week 16 and by 76% (16/21) at the end of follow-up. The proportion of patients using corticosteroids decreased from 48% to 25% at week 16 and to 13% at the end of the follow-up. Conclusion: UST showed to be effective and persistent, inducing short-term clinical benefit and endoscopic response in this real-life nationwide study of CD patients. Significant corticosteroid tapering in patients with highly treatment refractory and long-standing CD was observed.
Osteoclast-Released Wnt-10b Underlies Cinacalcet Related Bone Improvement in Chronic Kidney Disease

Secondary hyperparathyroidism (SHPT) relates to high turnover bone loss and is responsible for most bone fractures among chronic kidney disease (CKD) patients. Changes in the Wingless/beta-catenin signaling (Wnt/β-catenin) pathway and Wnt inhibitors have been found to play a critical role in CKD related bone loss. A calcimimetic agent, cinacalcet, is widely used for SHPT and found to be similarly effective for parathyroidectomy clinically. A significant decrease in hip fracture rates is noted among US hemodialysis Medicare patients since 2004, which is probably related to the cinacalcet era. In our previous clinical study, it was proven that cinacalcet improved the bone mineral density (BMD) even among severe SHPT patients. In this study, the influence of cinacalcet use on bone mass among CKD mice was determined. Cinacalcet significantly reduced the cortical porosity in femoral bones of treated CKD mice. It also improved the whole-bone structural properties through increased stiffness and maximum load. Cinacalcet increased femoral bone wingless 10b (Wnt10b) expression in CKD mice. In vitro studies revealed that cinacalcet decreased osteoclast bone resorption and increased Wnt 10b release from osteoclasts. Cinacalcet increased bone mineralization when culturing the osteoblasts with cinacalcet treated osteoclast supernatant. In conclusion, cinacalcet increased bone quantity and quality in CKD mice, probably through increased bone mineralization related with osteoclast Wnt 10b secretion.
The Metallophosphoesterase-Domain-Containing Protein 2 (MPPED2) Gene Acts as Tumor Suppressor in Breast Cancer

Background: We have recently reported the downregulation of the Metallophosphoesterase-domain-containing protein 2 (MPPED2) gene and its cognate long non-coding RNA, MPPED2-AS1, in papillary thyroid carcinomas. Functional studies supported a tumor suppressor role of both these genes in thyroid carcinogenesis. We then decided to investigate their role in breast carcinogenesis. Methods: In order to verify MPPED2 expression, 45 human breast carcinoma samples have been investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Then, MPPED2 has been transfected in several human breast carcinoma cell lines, analyzing its role in cell proliferation, migration and invasion. To study the regulation of MPPED2 expression the methylation of its promoter was investigated by targeted bisulfite sequencing. Results: MPPED2 expression was decreased in breast cancer samples, and this was confirmed by the analysis of data available in The Cancer Genome Atlas (TCGA). Interestingly, the hypermethylation of MPPED2 promoter likely accounted for its downregulation in breast cancer. Additionally, MPPED2-AS1 was also found downregulated in breast cancer tissues and, intriguingly, its expression decreased the hypermethylation of the MPPED2 promoter by inhibiting DNA methyltransferase 1 (DNMT1). Furthermore, the restoration of MPPED2 expression reduced cell proliferation, migration and invasion capability of breast carcinoma cell lines. Conclusion: Taken together, these results propose MPPED2 downregulation as a critical event in breast carcinogenesis.
Early lifecycle UV‐exposure calibrates adult vitamin D metabolism: Evidence for a developmentally originated vitamin D homeostat that may alter related adult phenotypes

Within the Developmental Origins of Adult Disease (DOHaD) model, early life environmental exposures can confer a long‐term legacy on human health. This mechanism may be adaptive or maladaptive depending on lifestyle circumstances. This article examines the role of first trimester UV‐exposure on late‐life vitamin D levels, and potentially related adaptive and maladaptive phenotypes (height and osteoporosis respectively).
Sweet neurons inhibit texture discrimination by signaling TMC-expressing mechanosensitive neurons in Drosophila

Integration of stimuli of different modalities is an important but incompletely understood process during decision making. Here, we show that Drosophila are capable of integrating mechanosensory and chemosensory information of choice options when deciding where to deposit their eggs. Specifically, females switch from preferring the softer option for egg-laying when both options are sugar free to being indifferent between them when both contain sucrose. Such sucrose-induced indifference between options of different hardness requires functional sweet neurons, and, curiously, the Transmembrane Channel-like (TMC)-expressing mechanosensitive neurons that have been previously shown to promote discrimination of substrate hardness during feeding. Further, axons of sweet neurons directly contact axons of TMC-expressing neurons in the brain and stimulation of sweet neurons increases Ca2+ influx into axons of TMC-expressing neurons. These results uncover one mechanism by which Drosophila integrate taste and tactile information when deciding where to deposit their eggs and reveal that TMC-expressing neurons play opposing roles in hardness discrimination in two different decisions.
Meibomian gland inversion: under‐recognized entity

To describe a clinical entity of upper eyelid margin and meibomian gland inversion (MGI) sequential to meibomian gland dysfunction (MGD), in the absence of eyelash ptosis, trichiasis or manifest marginal entropion. We highlight its clinical features, surgical management and outcomes.
Vocal Motor Performance in Birdsong Requires Brain–Body Interaction

Significance statement Motor skill learning typically occurs in a period when the brain needs to navigate a body that is still growing and developing. How the changing body, neural circuit formation and motor coding influence each other remains unknown. Songbirds provide excellent model systems to study motor skill learning. It has recently been shown that songbird vocal muscles double in speed during sensorimotor learning. Here we argue that these contractile as well as morphological changes stem predominantly from use and only secondarily from hormones or genetic programs. This implies that muscle training constrains skill learning trajectories. As contractile muscle property changes must require altered motor codes for achieving the same acoustic targets, the final performance results from interactions between brain and body.
Selective use of primate CD4 receptors by HIV-1

Individuals chronically infected with HIV-1 harbor complex viral populations within their bloodstreams. Recently, it has come to light that when these people infect others, the new infection is typically established by only one or a small number of virions from within this complex viral swarm. An important goal is to characterize the biological properties of HIV-1 virions that seed and exist early in new human infections because these are potentially the only viruses against which a prophylactic HIV-1 vaccine would need to elicit protection. This includes understanding how the Envelope (Env) protein of these virions interacts with the T-cell receptor CD4, which supports attachment and entry of HIV-1 into target cells. We examined early HIV-1 isolates for their ability to infect cells via the CD4 receptor of 15 different primate species. Primates were the original source of HIV-1 and now serve as valuable animal models for studying HIV-1. We find that most primary isolates of HIV-1 from the blood, including early isolates, are highly selective and enter cells through some primate CD4 receptor orthologs but not others. This phenotype is remarkably consistent, regardless of route of transmission, viral subtype, or time of isolation post infection. We show that the weak CD4 binding affinity of blood-derived HIV-1 isolates is what makes them sensitive to the small sequence differences in CD4 from one primate species to the next. To substantiate this, we engineered an early HIV-1 Env to have high, medium, or low binding affinity to CD4, and we show that it loses the ability to enter cells via the CD4 receptor of many primate species as the binding affinity gets weaker. Based on the phenotype of selective use of primate CD4, we find that weak CD4 binding appears to be a nearly universal property of HIV-1 circulating in the bloodstream. Therefore, weak binding to CD4 must be a selected and important property in the biology of HIV-1 in the body. We identify six primate species that encode CD4 receptors that fully support the entry of early HIV-1 isolates despite their low binding affinity for CD4. These findings will help inform long-standing efforts to model HIV-1 transmission and early disease in primates.
Lycopene alleviates AFB1-induced immunosuppression by inhibiting oxidative stress and apoptosis in the spleen of mice.

Lycopene (LYC) has been reported to exhibit antioxidant and immunoprotective activities, and our previous studies confirmed that LYC can alleviate multiple tissue damage induced by aflatoxin B1 (AFB1). However, it is unclear whether LYC could relieve the AFB1-induced immunosuppression. Thus, forty-eight male mice were randomly allocated and treated with LYC (5 mg kg-1) and/or AFB1 (0.75 mg kg-1) by intragastric administration for 30 days. We found that LYC alleviated AFB1-induced immunosuppression by relieving splenic structure injury and increasing the spleen weight, spleen coefficient, T lymphocyte subsets, the contents of IL-2, IFN-γ and TNF-α in serum, as well as the mRNA expression of IL-2, IFN-γ and TNF-α in spleen. Furthermore, LYC inhibited oxidative stress induced by AFB1 via decreasing the levels of reactive oxygen species (ROS), hydrogen peroxide (H2O2) and malondialdehyde (MDA), while enhancing the total antioxidant capacity (T-AOC) and antioxidant enzyme activities. In addition, LYC also restrained splenic apoptosis through blocking mitochondria-mediated apoptosis in AFB1 intoxicated mice, presenting as the increase of mitochondrial membrane potential, and the decrease of cytoplasmic Cyt-c protein expression, cleaved Caspase-3 protein expression, Caspase-3/9 activities and mRNA expressions, as well as balancing the mitochondrial protein and mRNA expressions of Bax and Bcl-2. These results indicate that LYC can alleviate AFB1-induced immunosuppression by inhibiting oxidative stress and mitochondria-mediated apoptosis of mice spleen.
Restoring pulsatility and peakVO2 in the era of continuous flow, fixed pump speed, left ventricular assist devices: ‘A hypothesis of pump's or patient's speed?’

Despite significant improvement in survival and functional capacity after continuous flow left ventricular assist device implantation, the patient's quality of life may remain limited by complications such as aortic valve insufficiency, thromboembolic episodes and gastrointestinal bleeding attributed to high shear stress continuous flow with attenuated or absence of pulsatile flow and by a reduced peak oxygen consumption (peakVO2) primarily associated with a fixed pump speed operation. Revision of current evidence suggests that high technology pump speed algorithms, a ‘hypothesis of decreasing pump's speed’ to promote pulsatile flow and a ‘hypothesis of increasing pump's speed’ to increase peakVO2, may only partially reverse these barriers. A ‘hypothesis of increasing patient's speed’ is introduced, suggesting that exercise training may further contribute to the patient's recovery, enhancing peakVO2 and pulsatile flow by improving skeletal muscle oxidative capacity and strength, peripheral vasodilatory and ventilatory responses, favour changes in preload/afterload and facilitate native flow, formulating the rationale for further studies in the field.
Nutrient Intakes from Meals and Snacks Differ with Age in Middle-Aged and Older Americans

The present study investigated the meal patterns across demographic characteristics in middle-aged and older US adults. Study participants were noninstitutionalized participants from the 2005–2016 National Health and Nutrition Examination Survey, an observational cross-sectional study. Data from 17,361 adults were categorized into 45–59 years (n = 7366), 60–70 years (n = 5348), and 71+ years (n = 4647) to compare demographics, nutrient intakes, and meal patterns. Dietary recalls were collected using the multiple-pass method. Data analyses were weighted to create a nationally representative sample. Two-thirds of adults reported consuming three meals on the day of intake. Lunch was the most often skipped meal across all age groups. A greater proportion of adults over 70 years reported consuming breakfast, while a smaller proportion reported consuming snacks. Significant differences were observed in total energy and nutrient intakes and proportion of the day’s intakes by meal. Grain, milk, and dairy food group intakes were highest at breakfast, while the protein food group intakes were highest at lunch and dinner. Age-related differences in meal consumption and composition provide valuable formative data to support targeted nutritional education and intervention opportunities to promote and encourage healthy food choices.
Prevention and Treatment of Sarcopenic Obesity in Women

Sarcopenic obesity (SO) is referred to as the combination of obesity with low skeletal muscle mass and function. However, its definition and diagnosis is debated. SO represents a sizable risk factor for the development of disability, possibly with a worse prognosis in women. The present narrative review summarizes the current evidence on pharmacological, nutrition and exercise strategies on the prevention and/or treatment of SO in middle-aged and older-aged women. A literature search was carried out in Medline and Google Scholar between 29th January and 14th March 2019. Only controlled intervention studies on mid-age and older women whose focus was on the prevention and/or treatment of sarcopenia associated with obesity were included. Resistance training (RT) appears effective in the prevention of all components of SO in women, resulting in significant improvements in muscular mass, strength, and functional capacity plus loss of fat mass, especially when coupled with hypocaloric diets containing at least 0.8 g/kg body weight protein. Correction of vitamin D deficit has a favorable effect on muscle mass. Treatment of SO already established is yet unsatisfactory, although intense and prolonged RT, diets with higher (1.2 g/kg body weight) protein content, and soy isoflavones all look promising. However, further confirmatory research and trials combining different approaches are required.
The Effect of Teamwork on Children With Cleft Lip and Palate and Their Mother’s Quality of Life

Objective: Maintaining and improving patients’ quality of life (QOL) are regarded as the most important aims in health-care systems. These are directly associated with intervention of health-care providers across the world. The aim of the present study was to evaluate the impact of teamwork on frequency of care provided to children with cleft lip and palate and their mothers’ QOL. Methods: This analytical epidemiology study was conducted on 101 children with cleft lip and palate and their mothers who were divided into 2 groups: a multidisciplinary team and a group of individual providers. Data were collected using convenience sampling. Quality of Life Questionnaire (Short Form-36) was assessed. The statistical analysis was performed using the χ2 test, independent t test, and Mann-Whitney U test in SPSS (20). Results: Both groups were matched. There was a significant statistical difference among the members of multidisciplinary team who received surgery, genetic counseling, and dental care (P ≤ .043) and the individual providers groups. The 2 groups did not have significant difference in receiving the hearing test, speech therapy, and dental care 12 months before the interview. There were significant differences in QOL scores between the multidisciplinary team and the group of individual providers (P = .013). Conclusions: The services provided as a multidisciplinary team leads to a better outcome and improves the QOL of our patients and their families. It is recommended that services should be provided in the team approach for patients with cleft lip and palate.
gga-miRNA-18b-3p Inhibits Intramuscular Adipocytes Differentiation in Chicken by Targeting the ACOT13 Gene

Intramuscular fat (IMF) is the most important evaluating indicator of chicken meat quality, the content of which is positively correlated with tenderness, flavor, and succulence of the meat. Chicken IMF deposition process is regulated by many factors, including genetic, nutrition, and environment. Although large number of omics’ studies focused on the IMF deposition process, the molecular mechanism of chicken IMF deposition is still poorly understood. In order to study the role of miRNAs in chicken intramuscular adipogenesis, the intramuscular adipocyte differentiation model (IMF-preadipocytes and IMF-adipocytes) was established and subject to miRNA-Seq. A total of 117 differentially expressed miRNAs between two groups were obtained. Target genes prediction and functional enrichment analysis revealed that eight pathways involved in lipid metabolism related processes, such as fatty acid metabolism and fatty acid elongation. Meanwhile a putative miRNA, gga-miR-18b-3p, was identified be served a function in the intramuscular adipocyte differentiation. Luciferase assay suggested that the gga-miR-18b-3p targeted to the 3′UTR of ACOT13. Subsequent functional experiments demonstrated that gga-miR-18b-3p acted as an inhibitor of intramuscular adipocyte differentiation by targeting ACOT13. Our findings laid a new theoretical foundation for the study of lipid metabolism, and also provided a potential target to improve the meat quality in the poultry industry.
Unintentional injury and role of different predictors among 1–5 years children: a community based cross sectional study in a rural population of a developing country

Abstract Injury has been increasing exponentially, especially in children, and it has become a public health concern. The present study was conducted with the objective of determining the prevalence and profile of unintentional injury among children of 1–5-year age group in a rural community of India and also to find out the predictors. Primary caregiver was interviewed by using a structured interview schedule. Parent supervisory behaviour was assessed using Parent Supervision Attributes Profile Questionnaire (PSAPQ), and child injury risk-taking behaviour was assessed by using injury behaviour checklist (IBC). Children encountered any unintentional injury event during last three-month period were 261 (62.7%). PSAPQ score was significantly higher in those parents where children had no episode of injury compared to others. Among four components of the PSAPQ, protectiveness (p = 0.049) and risk tolerance (p = 0.001) score had significant positive association with the incidence of unintentional injury. Binary multivariable logistic regression technique had found that age of the child, gender, primary care giver, birth order of the baby, the number of siblings, social class and IBC score has significant association with history of unintentional injury. There is utmost need for the development of effective programmes and training strategies to prevent unintentional injury among under-five children in future.
Risk factors of stunting (chronic undernutrition) of children aged 6 to 24 months in Mekelle City, Tigray Region, North Ethiopia: An unmatched case-control study

Introduction In 2014, 159 million under 5 year-old children were stunted (suffered chronic undernutrition) worldwide. Identifying risk factors for stunting among 6 to 24 month-age children in Mekelle City is important for evidence-based interventions. Method Case-Control study design was undertaken in 330 children, from January to February 2016. World Health Organization (WHO) anthropometric software and statistical package for social sciences version 20 were used for analysis. Logistic regression analysis was applied. Result The following were identified as risk factors for stunting: mother’s lack of formal education (adjusted odds ratio (AOR = 6.4)), mother height less than 150cm (AOR = 4.2), mother with a body mass index less than 18.5 kg/m2 (AOR = 3.8), childbirth weight less than 2.5kg (AOR = 5.3), household with two and above under-five children (AOR = 2.9), a WHO diet diversity score < 4 (AOR = 3.2) and repeated diarrheal episodes (AOR = 5.3). Conclusion The factors associated with stunting among children aged 6 to 24 months are no formal education in mother, mother height less than 150cm, low BMI of the mother, low birth weight, low WHO DDS, number of under 5 children in the household and repeated diarrheal episodes. Nutritional interventions should give emphasis to maternal education, maternal nutrition, childbirth weight, family size, diet diversity, and diarrheal diseases.