Miracle-dz/UniFAR-FTUs huggingface dataset:
Imbalance of nonparametric rest-activity rhythm and the evening-type of chronotype according to frailty indicators in elderly community dwellers

ABSTRACT Background: Sleep health-related issues, such as poor subjective sleep quality during the night and nocturnal wakefulness, have been a focus of recent research on frailty. However, current trends regarding the chronotypes of older individuals with frailty have not been well documented, and information on the impact of frailty on circadian rest-activity patterns is limited. The aim of this research was to clarify the relationship among frailty, nonparametric rest-activity patterns, and chronotype in older community-dwelling subjects. Method: A survey was conducted between June and December 2018, and the participants of this study were recruited from among community-dwellers aged 60 years or older living in Akita prefecture, Japan. The frailty phenotype defined by the National Center for Geriatrics and Gerontology Study of Geriatric Syndromes (NCGG-SGS) was used to evaluate the frailty status of each participant. To evaluate nonparametric rest-activity rhythm (RAR) parameters (e.g., interdaily stability [IS], intradaily variability [IV], and relative amplitude [RA]), each participant wore an Actiwatch Spectrum Plus device on his or her non-dominant wrist for seven continuous days without removal. The Munich chronotype questionnaire-Japanese version (MCTQ-J) was also used to measure the midpoint of sleep in free days (MSF). Results: The final study cohort was composed of 105 participants (85.7% women) and was divided into 58 non-frail subjects, 45 pre-frail subjects, and 2 frail subjects. According to a binomial logistic regression analysis, the pre-frail individuals had a weaker grip strength (coefficient [beta], −0.18; odds ratio, 0.84; 95% confidence interval [CI], 0.76–0.93; p = .001) and a lower RA (beta, −8.78; odds ratio, 0.0002; 95% CI, 0.00–0.15; p = .01). In addition, correlation analyses also showed that the MSF was negatively associated with the RA in the pre-frail group (r = −0.30, p < .05) and positively correlated with the RA in the non-frail group (r = 0.26, p < .05); furthermore, the MSF of the pre-frail group occurred at a later time than that of the non-frail one (p = .03). Conclusion: The present study provides grounds for our proposal that pre-frailty is significantly associated with a low grip power and relative imbalance between rest and active statuses as indexed using nonparametric RAR parameters. Furthermore, elderly individuals with pre-frailty or frailty may have a later MSF time. However, these potential findings need to be validated in future research.
Risk Factors for Predicting Osteoporosis in Patients Who Receive Thyrotropin Suppressive Levothyroxine Treatment for Differentiated Thyroid Carcinoma

Objectives: Endogenous hyperthyroidism accelerates bone turnover and shortens the normal bone remodeling cycle, which results in reduced bone density. It is estimated that suppressive levothyroxine (LT4) therapy also decreases bone density. The aim of this study was to define risk factors for osteoporosis development in patients under thyrotropin-stimulating hormone (TSH) suppressive treatment for differentiated thyroid cancer (DTC). Methods: Patients with a diagnosis of low or intermediate risk group DTC according to the American Thyroid Association 2015 guidelines and who have been receiving LT4 suppression therapy and were physically fit to undergo femur and lumbar vertebra bone density study were included in the study. Patients lacking information on demographic data, medical history, preoperative thyroid hormone status, or routine follow-up data were excluded from the study. A study form consisting of patient information on possible risk factors for osteoporosis such as gender, age, menopausal status, smoking, family history of osteoporosis, preoperative thyroid hormone status, postoperative hypoparathyroidism history, mean serum TSH levels, and duration of TSH suppression was created and filled out for each participant. Bone mineral densitometries of the femur and lumbar vertebrae were measured along with serum vitamin D and parathyroid hormone levels. Results: During TSH suppression (mean 7.2±4.5 years, range: 1-26), osteoporosis was detected in 89 (9.6%) patients. The mean time to develop osteoporosis was significantly different in patients with or without a family history of osteoporosis (15.3±0.4 versus 20.3±0.6 years; p=0.002). Similarly, the mean time to develop osteoporosis for was found to be significantly shorter in postmenopausal patients than that for premenopausal women (18.6±0.7 versus 20.4±0.4 years; p<0.001). Male gender (p<0.001), a family history of osteoporosis (p=0.001) and menopausal state (p<0.001) were identified as independent predictive factors for developing osteoporosis. Conclusion: Postmenopausal women, men, and patients with a family history who receive TSH-suppression treatment have a tendency to develop osteoporosis.
Reduced grey matter volume in frontal and temporal areas in depression: contributions from voxel-based morphometry study

Abstract Objective: The aim of the current study was to examine whether and to what extent mood disorders, comprising major depression and bipolar disorder, are accompanied by structural changes in the brain as measured using voxel-based morphometry (VBM). Methods: We performed a VBM study using a 3Т MRI system (GE Discovery 750w) in patients with mood disorders (n=50), namely, 39 with major depression and 11 with bipolar disorder compared to 42 age-, sex- and education-matched healthy controls. Results: Our results show that depression was associated with significant decreases in grey matter (GM) volume of the regions located within the medial frontal and anterior cingulate cortex on the left side and middle frontal gyrus, medial orbital gyrus, inferior frontal gyrus (triangular and orbital parts) and middle temporal gyrus (extending to the superior temporal gyrus) on the right side. When the patient group was separated into bipolar disorder and major depression, the reductions remained significant only for patients with major depressive disorder. Conclusions: Using VBM the present study was able to replicate decreases in GM volume restricted to frontal and temporal regions in patients with mood disorders, mainly major depression, compared with healthy controls.
Anti-Obesity Effects of Dietary Calcium: The Evidence and Possible Mechanisms

Obesity is a serious health challenge worldwide and is associated with various comorbidities, including dyslipidemia, type 2 diabetes, and cardiovascular disease. Developing effective strategies to prevent obesity is therefore of paramount importance. One potential strategy to reduce obesity is to consume calcium, which has been implicated to be involved in reducing body weight/fat. In this review, we compile the evidence for the anti-obesity roles of calcium in cells, animals, and humans. In addition, we summarize the possible anti-obesity mechanisms of calcium, including regulation of (a) adipogenesis, (b) fat metabolism, (c) adipocyte (precursor) proliferation and apoptosis, (d) thermogenesis, (e) fat absorption and excretion, and (f) gut microbiota. Although the exact anti-obesity roles of calcium in different subjects and how calcium induces the proposed anti-obesity mechanisms need to be further investigated, the current evidence demonstrates the anti-obesity effects of calcium and suggests the potential application of dietary calcium for prevention of obesity.
How Many Mammalian Reovirus Proteins are involved in the Control of the Interferon Response?

As with most viruses, mammalian reovirus can be recognized and attacked by the host-cell interferon response network. Similarly, many viruses have developed resistance mechanisms to counteract the host-cell response at different points of this response. Reflecting the complexity of the interferon signaling pathways as well as the resulting antiviral response, viruses can—and often have—evolved many determinants to interfere with this innate immune response and allow viral replication. In the last few years, it has been evidenced that mammalian reovirus encodes many different determinants that are involved in regulating the induction of the interferon response or in interfering with the action of interferon-stimulated gene products. In this brief review, we present our current understanding of the different reovirus proteins known to be involved, introduce their postulated modes of action, and raise current questions that may lead to further investigations.
Comprehension: A Paradigm for Cognition

Preface Acknowledgements 1. Introduction Part I. The Theory: 2. Cognition and representation 3. Propositional representations 4. Modeling comprehension processes: the construction-integration model Part II. Models of Comprehension: 5. Word identification in discourse 6. Textbases and situation models 7. The role of working memory in comprehension 8. Memory for text 9. Learning from text 10. Word problems 11. Beyond text References name index Subject index.
Postnatal Alveologenesis Depends on FOXF1 Signaling in c-KIT+ Endothelial Progenitor Cells.

RATIONALE Disruption of alveologenesis is associated with severe pediatric lung disorders, including Bronchopulmonary Dysplasia (BPD). While c-KIT+ endothelial (EC) progenitor cells are abundant in embryonic and neonatal lungs, their role in alveolar septation and the therapeutic potential of these cells remain unknown. OBJECTIVE To determine whether c-KIT+ EC progenitor cells stimulate alveologenesis in the neonatal lung. METHODS We used single cell RNA sequencing of neonatal human and mouse lung tissues, immunostaining and FACS analysis to identify transcriptional and signaling networks shared by human and mouse pulmonary c-KIT+ EC progenitors. A mouse model of perinatal hyperoxia-induced lung injury was employed to identify molecular mechanisms critical for survival, proliferation and engraftment of c-KIT+ EC progenitors in the neonatal lung. MEASUREMENTS AND MAIN RESULTS Pulmonary c-KIT+ EC progenitors expressing PECAM-1, CD34, VE-Cadherin, FLK1 and TIE2 lacked mature arterial, venal and lymphatic cell surface markers. The transcriptomic signature of c-KIT+ ECs is conserved in mouse and human lungs and is enriched in FOXF1-regulated transcriptional targets. Expression of FOXF1 and c-KIT are decreased in lungs of infants with BPD. In the mouse, neonatal hyperoxia decreases the number of c-KIT+ EC progenitors. Haploinsufficiency or endothelial-specific deletion of Foxf1 in mice increases apoptosis and decreases proliferation of c-KIT+ ECs. Inactivation of either Foxf1 or c-Kit causes alveolar simplification. Adoptive transfer of c-KIT+ ECs into the neonatal circulation increases lung angiogenesis and prevents alveolar simplification in neonatal mice exposed to hyperoxia. CONCLUSIONS Cell therapy involving c-KIT+ EC progenitors can be beneficial for treatment of BPD.
Efficiency of Health Care Risk Waste Management in Rural Healthcare Facilities of South Africa: An Assessment of Selected Facilities in Vhembe District, Limpopo Province

Waste generated form healthcare facilities is a potential source of health risks to the public, if it is not properly handled from the point of generation to disposal. This study was conducted to assess the efficiency of healthcare risk waste (HCRW) management in Vhembe District of Limpopo Province, South Africa. Fifteen healthcare facilities were selected in Vhembe District for this study. Data were obtained through in-depth interviews, semi-structured questionnaires, observation and pictures. Qualitative data were thematically analyzed, while the quantitative data were analyzed using the Statistical Package for the Social Sciences, version 25. In all the healthcare facilities; mismanagement of HCRW was noted at different points along the management chain. Poor segregation, overfilling of waste bins, inappropriate transportation and storage of waste in substandard storage rooms were observed in the facilities. All the waste from the district are transported to a private-owned treatment facility outside the district, where they are mainly incinerated. Enforcement of healthcare risk waste guidelines, provision of standardized equipment for temporary storage, empowerment of each healthcare facility to treat at least some of the waste, and employment of non-burn techniques for treatment of waste are recommended for more efficient management of healthcare risk waste in Vhembe District.
Recent Advances in Pharmaceutical Potential of Brown Algal Polysaccharides and their Derivatives.

Marine plants, animals and microorganisms display steady growth in the ocean and are abundant carbohydrate resources. Specifically, natural polysaccharides obtained from brown algae have been drawing increasing attention owing to their great potential in pharmaceutical applications. This review describes the structural and biological features of brown algal polysaccharides, including alginates, fucoidans, and laminarins, and it highlights recently developed approaches used to obtain the oligo- and polysaccharides with defined structures. Functional modification of these polysaccharides promotes their advanced applications in biomedical materials for controlled release and targeted drug delivery, etc. Moreover, brown algal polysaccharides and their derivatives possess numerous biological activities with anticancer, anticoagulant, wound healing, and antiviral properties. In addition, we also discuss carbohydrate-based substrates from brown algae, which are currently in clinical and preclinical studies, as well as the marine drugs that are already on the market. The present review summarizes the recent development of carbohydrate-based products from brown algae, with promising findings that could rapidly facilitate the future discovery of novel marine drugs.
miR‐942 promotes tumor migration, invasion, and angiogenesis by regulating EMT via BARX2 in non‐small‐cell lung cancer

Epithelial–mesenchymal transition (EMT) has an important function in cancer. Recently, microRNAs have been reported to be involved in EMT by regulating target genes. miR‐942 is considered a novel oncogene in esophageal squamous cell carcinoma. However, its role in non‐small‐cell lung cancer (NSCLC) has not been investigated. In this study, the expression of miR‐942 in NSCLC patients tumor and paired adjacent tissues were assessed by quantitative real‐time polymerase chain reaction and in situ hybridization. Transwell, wound healing, tube formation, and tail vein xenograft assays were conducted to assess miR‐942′s function in NSCLC. Potential miR‐942 targets were confirmed using dual‐luciferase reporter assays, immunohistochemistry, immunoblot, and rescue experiments. The results showed miR‐942 is relatively highly expressed in human NSCLC tissues and cells. In vitro assays demonstrated that overexpression of miR‐942 promoted cell migration, invasion, and angiogenesis. Tail vein xenograft assays suggested that miR‐942 contributed to NSCLC metastasis in vivo. Three bioinformatics software was searched, and BARX2 was predicted as a downstream target of miR‐942. Direct interaction between them was validated by dual‐luciferase assays. Rescue experiments further confirmed that BARX2 overexpression could reverse functional changes caused by miR‐942. Moreover, miR‐942 increased EMT‐associated proteins N‐cadherin and vimentin by inhibiting BARX2, while E‐cadherin expression is reduced. In summary, this study reveals that miR‐942 induces EMT‐related metastasis by directly targeting BARX2, which may provide a potential therapeutic strategy for NSCLC.
Dietary Inflammatory Index, Dietary Non-Enzymatic Antioxidant Capacity, and Colorectal and Breast Cancer Risk (MCC-Spain Study)

Inflammation and antioxidant capacity have been associated with colorectal and breast cancer. We computed the dietary inflammatory index (DII®), and the total dietary non-enzymatic antioxidant capacity (NEAC) and associated them with colorectal and breast cancer risk in the population-based multi case-control study in Spain (MCC-Spain). We included 1852 colorectal cancer and 1567 breast cancer cases, and 3447 and 1486 population controls, respectively. DII score and NEAC were derived using data from a semi-quantitative validated food frequency questionnaire. Unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95%CI) for energy-adjusted DII (E-DII), and a score combining E-DII and NEAC. E-DII was associated with colorectal cancer risk (OR = 1.93, highest quartile versus lowest, 95%CI:1.60–2.32; p-trend: <0.001); this increase was observed for both colon and rectal cancer. Less pronounced increased risks were observed for breast cancer (OR = 1.22, highest quartile versus lowest, 95%CI:0.99–1.52, p-trend: >0.10). The combined score of high E-DII scores and low antioxidant values were associated with colorectal cancer risk (OR = 1.48, highest quartile versus lowest, 95%CI: 1.26–1.74; p-trend: <0.001), but not breast cancer. This study provides evidence that a pro-inflammatory diet is associated with increased colorectal cancer risk while findings for breast cancer were less consistent.
Improving Communication in Breast Cancer Treatment Consultation: Use of a Computer Test of Health Numeracy.

Background: Communication of statistics and probability is challenging in the cancer care setting. The objectives of this study are to evaluate a novel approach to cancer communication through the use of a computer assessment of patient health numeracy. Methods: We conducted a pilot study of the Computer Adapted Test of Numeracy Understanding in Medicine Instrument (CAT-NUMi) before the cancer treatment consultation for women with stage 0-3 breast cancer. Patient outcomes included the interpersonal processes of care (IPC) and the decisional conflict scale. We evaluated clinician use of numeric information in the cancer consultation and assessed feasibility outcomes from the clinician and patient perspective. Results: Patient participants (n = 50) had a median (interquartile range) age of 51 years (46-61), 70% were English speaking, and 30% Spanish speaking. Decisional conflict was low with a mean (standard deviation [SD]) decisional conflict score of 17.4 (12.3). The lack of clarity score (range 1-5) on the IPC was low (mean, SD),1.70 (0.71), indicating clear communication. Clinicians more often used percentages in communicating prognosis among those with higher numeracy scores (median, range): high (2, 0-8), medium (1, 0-7), and low (0, 0-8); p = 0.04. The patient experience of taking the CAT-NUMi was rated as very good or excellent by 65%, fair by 33%, and poor by 2% of patients. Conclusion: Screening for health numeracy with a short computer-based test may be a feasible strategy to optimize clear communication in the cancer treatment consultation. Further studies are needed to evaluate this strategy across cancer treatment clinical settings and populations.
Implication of Kv7 Channels in the Spinal Antinociceptive Actions of Celecoxib

Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) commonly used to treat pain conditions in humans. In addition to its blocking activity on cyclooxygenase (COX) enzymes, several other targets could contribute to its analgesic activity. Here we explore the spinal antinociceptive actions of celecoxib and the potential implication of Kv7 channels in mediating its effects. Spinal cord in vitro preparations from hind paw-inflamed animals were used to assess the segmental sensory-motor and the early sensory processing of nociceptive information. Electrophysiological recordings of ventral roots and dorsal horn neurones were obtained, and the effects of celecoxib and Kv7 modulators on responses to repetitive dorsal root stimulation at C-fiber intensity were assessed. Celecoxib applied at clinically relevant concentrations produced depressant effects on responses to dorsal root stimulation recorded from both ventral roots and individual dorsal horn neurones; by contrast, the non-nociceptive monosynaptic reflex was unaffected. The NSAID indomethacin had no effect on spinal reflexes, but further coapplication of celecoxib still produced depressant effects. The depressant actions of celecoxib were abolished after Kv7 channel blockade and mimicked by its structural analog dimethyl-celecoxib, which lacks COX-blocking activity. The present results identify Kv7 channels as novel central targets for celecoxib, which may be relevant to its analgesic effect. This finding contributes to better understand the pharmacology of celecoxib and reinforces both the role of Kv7 channels in modulating the excitability of central pain pathways and its validity as target for the design of analgesics.
An optimized 5/6 nephrectomy mouse model based on unilateral kidney ligation and its application in renal fibrosis research

Abstract 5/6 Nephrectomy (PNx) on rat and mouse mimics renal failure after loss of kidney function in human, and it has been widely used in CKD researches. However, existing methods for PNx model construction present high mortality of animals after modeling due to hemorrhage and infection in or after surgery. Here, we report a novel and highly efficient PNx modeling method to simulate conventional 5/6 nephrectomy, which significantly reduced the mortality of animals and simplified the modeling procedures. In this novel modeling method, we directly ligated the upper and lower poles of left kidney after removal the right kidney 1 week later (l-PNx), which leads to necrosis of ligated upper and lower poles of the kidney and mimics the conventional 5/6 nephrectomy (c-PNx). After modeling 4 and 12 weeks, the serum creatinine, BUN and proteinuria levels were strongly increased in both c-PNx and l-PNx model. Importantly, compared with the c-PNx, l-PNx model present more severe renal fibrosis estimated by Masson staining, IHC and western blotting. The results showed that the protein levels of α-SMA were significantly increased in the kidney of c-PNx and l-PNx models, but more increase was found in l-PNx model. It is noteworthy that, compared with c-PNx model, the survival rate of l-PNx model was markedly increased. In summary, we established a novel and efficient 5/6 nephrectomy model, which can mimic conventional 5/6 nephrectomy to construct a renal fibrosis and renal failure mouse model, that is conducive to mechanism and treatment researches of CKD.