Miracle-dz/UniFAR-FTUs huggingface dataset:
Bone turnover during inpatient nutritional therapy and outpatient follow-up in patients with anorexia nervosa compared with that in healthy control subjects.

BACKGROUND Osteopenia and osteoporosis are among the most frequent and severe complications in adolescents with anorexia nervosa. OBJECTIVE The aim of this study was to assess the influence of nutritional therapy on bone metabolism during adolescent anorexia nervosa. DESIGN We studied 19 anorectic patients aged 14.1 +/- 1.4 y (x +/- SD) with a body mass index (BMI; in kg/m(2)) of 14.2 +/- 1.4 and 19 age-matched control subjects aged 15.1 +/- 2.3 y with a BMI of 20.8 +/- 1.9 for 1 y. Blood samples were taken for the measurement of bone markers, insulin-like growth factor I (IGF-I), and leptin. RESULTS BMI rose significantly from 14.2 +/- 1.4 at baseline to 17.4 +/- 0.6 (P < 0.0001) at week 15. Compared with concentrations in the control subjects, concentrations of the bone formation markers procollagen type I propeptide (PICP) and bone alkaline phosphatase (bAP) in the anorectic patients were lower at baseline (PICP: P = 0.0071; bAP: P = 0.0012), increased with nutritional therapy (PICP: P = 0.0060, bAP: P = 0.0147), and were no longer significantly different (P > 0.05) during the follow-up period. Concentrations of IGF-I and leptin were significantly lower (P < 0.0001 for both) in the anorectic patients than in the control subjects at baseline. IGF-I increased with nutritional therapy but was still significantly lower (P = 0.0036) than that in the control group and decreased again during the follow-up period (P = 0.0126). In contrast, serum C-telopeptide decreased with nutritional therapy (P = 0.0446). CONCLUSION Nutritional therapy improves concentrations of bone formation markers in adolescent patients with anorexia nervosa.
The Paravascular Pathway for Brain Waste Clearance: Current Understanding, Significance and Controversy

The paravascular pathway, also known as the “glymphatic” pathway, is a recently described system for waste clearance in the brain. According to this model, cerebrospinal fluid (CSF) enters the paravascular spaces surrounding penetrating arteries of the brain, mixes with interstitial fluid (ISF) and solutes in the parenchyma, and exits along paravascular spaces of draining veins. Studies have shown that metabolic waste products and solutes, including proteins involved in the pathogenesis of neurodegenerative diseases such as amyloid-beta, may be cleared by this pathway. Consequently, a growing body of research has begun to explore the association between glymphatic dysfunction and various disease states. However, significant controversy exists in the literature regarding both the direction of waste clearance as well as the anatomical space in which the waste-fluid mixture is contained. Some studies have found no evidence of interstitial solute clearance along the paravascular space of veins. Rather, they demonstrate a perivascular pathway in which waste is cleared from the brain along an anatomically distinct perivascular space in a direction opposite to that of paravascular flow. Although possible explanations have been offered, none have been able to fully reconcile the discrepancies in the literature, and many questions remain. Given the therapeutic potential that a comprehensive understanding of brain waste clearance pathways might offer, further research and clarification is highly warranted.
PTEN genomic deletion is associated with p‐Akt and AR signalling in poorer outcome, hormone refractory prostate cancer

PTEN haploinsufficiency is common in hormone‐sensitive prostate cancer, though the incidence of genomic deletion and its downstream effects have not been elucidated in clinical samples of hormone refractory prostate cancer (HRPC). Progression to androgen independence is pivotal in prostate cancer and mediated largely by the androgen receptor (AR). Since this process is distinct from metastatic progression, we examined alterations of the PTEN gene in locally advanced recurrent, non‐metastatic human HRPC tissues. Retrospective analyses of PTEN deletion status were correlated with activated downstream phospho‐Akt (p‐Akt) pathway proteins and with the androgen receptor. The prevalence of PTEN genomic deletions in transurethral resection samples of 59 HRPC patients with known clinical outcome was assessed by four‐colour FISH analyses. FISH was performed using six BAC clones spanning both flanking PTEN genomic regions and the PTEN gene locus, and a chromosome 10 centromeric probe. PTEN copy number was also evaluated in a subset of cases using single nucleotide polymorphism (SNP) arrays. In addition, the samples were immunostained with antibodies against p‐Akt, p‐mTOR, p‐70S6, and AR. The PTEN gene was deleted in 77% of cases, with 25% showing homozygous deletions, 18% homozygous and hemizygous deletions, and 34% hemizygous deletions only. In a subset of the study group, SNP array analysis confirmed the FISH findings. PTEN genomic deletion was significantly correlated to the expression of downstream p‐Akt (p < 0.0001), AR (p = 0.025), and to cancer‐specific mortality (p = 0.039). PTEN deletion is common in HRPC, with bi‐allelic loss correlating to disease‐specific mortality and associated with Akt and AR deregulation. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Activation of visceral afferents by bradykinin and ischemia: independent roles of PKC and prostaglandins.

We have shown that the cyclooxygenase (COX) and protein kinase C (PKC) systems both contribute to afferent activation in response to bradykinin (BK) and abdominal ischemia. Because the contribution from PKC to C fiber activation may depend, in part, on prostaglandin production, we hypothesized that an intact COX system is required for PKC-induced activation of ischemically sensitive abdominal visceral afferents by BK and abdominal ischemia. Single-unit activity of abdominal visceral C fibers was recorded from the right thoracic sympathetic chain of anesthetized cats. Three repeated injections of BK (1-2 μg/kg ia) produced similar increases in afferent activity from the baseline of 1.32 ± 0.24, 1.37 ± 0.32, and 1.41 ± 0.24 impulses/s ( n = 5). In another group of animals ( n = 5), the second and third BK injections were performed after COX inhibition (indomethacin; 5 mg/kg iv) and then combined COX + PKC inhibition [PKC-(19-36), 20 μg/kg iv], respectively. Inhibition of COX reduced ( P < 0.05) the afferent response to BK (0.59 ± 0.12 impulses/s) compared with the unblocked condition (1.14 ± 0.27 impulses/s), whereas combined COX + PKC inhibition further attenuated the increase from baseline (0.18 ± 0.09 impulses/s; P < 0.05). Similar results were obtained in a third group of cats when the antagonists were administered in reverse order ( n = 7). In a fourth group of cats ( n = 9) that were pretreated with indomethacin, ischemia increased afferent activity (0.78 ± 0.17 impulses/s). However, neural activity was attenuated (0.51 ± 0.14 impulses/s; P < 0.05) during a second bout of ischemia in the presence of indomethacin + PKC-(19-36). These results suggest that the contribution from PKC to the activation of ischemically sensitive C fibers, particularly by BK, does not require an intact cyclooxygenase system.
Polymorphism of the 5-HT2A receptor gene and food intakes in children and adolescents: the Stanislas Family Study.

BACKGROUND Serotonin (5-hydroxytryptamine; 5-HT) is a key mediator in the control of food intake and is probably involved in the etiology of anorexia nervosa. An association between a polymorphism of the 5-HT receptor (5-HT2A) gene promoter (-1438G/A) and anorexia nervosa has been reported. OBJECTIVE We investigated the relation between the -1438G/A polymorphism of the 5-HT(2A) gene and the energy and macronutrient intakes of children and adolescents. DESIGN This cross-sectional study included 370 children and adolescents aged 10-20 y (176 boys and 194 girls from 251 families) drawn from the Stanislas Family Study. Energy and macronutrient intakes were assessed by using 3-d food records. The -1438G/A polymorphism was analyzed by polymerase chain reaction and then by Hpa II digestion. RESULTS In the overall group, after adjustment for age, sex, weight, height, and family correlation, the A allele was significantly associated with lower energy (P for trend = 0.045) and with total, monounsaturated, and saturated fat intakes expressed in g/d (P for trend = 0.007, 0.005, and 0.006, respectively). Subjects with the GA genotype had intermediate values. In addition, genotype x sex and genotype x age interactions were not significant. CONCLUSIONS The 5-HT2A gene polymorphism in the promoter region is associated with energy and fat intakes in young people. This could be explained by the role of the serotonergic system as a determinant of food intakes and eating behavior.
Tea consumption and cognitive impairment and decline in older Chinese adults.

BACKGROUND Laboratory research suggests that tea has potential neurocognitive protective effects, but this is not established in humans. OBJECTIVE We aimed to examine the relation between tea intake and cognitive impairment and decline. DESIGN Among community-living Chinese adults aged > or = 55 y in the Singapore Longitudinal Ageing Studies cohort, we measured tea consumption at baseline and administered the Mini-Mental State Examination (MMSE) at baseline and 1-2 y later. Cognitive impairment was defined as an MMSE score < or = 23 and cognitive decline as a drop in MMSE score of > or = 1 point. We performed cross-sectional analysis of baseline data from 2501 participants and longitudinal analysis of data from 1438 cognitively intact participants. Odds ratios (ORs) of association were calculated in logistic regression models that adjusted for potential confounders. RESULTS Total tea intake was significantly associated with a lower prevalence of cognitive impairment, independent of other risk factors. Compared with the ORs for rare or no tea intake, the ORs for low, medium, and high levels of tea intake were 0.56 (95% CI: 0.40, 0.78), 0.45 (95% CI: 0.27, 0.72), and 0.37 (95% CI: 0.14, 0.98), respectively (P for trend < 0.001). For cognitive decline, the corresponding ORs were 0.74 (95% CI: 0.54, 1.00), 0.78 (95% CI: 0.55, 1.11), and 0.57 (95% CI: 0.32, 1.03), respectively (P for trend = 0.042). These effects were most evident for black (fermented) and oolong (semi-fermented) teas, the predominant types consumed by this population. In contrast, no association between coffee intake and cognitive status was found. CONCLUSION Regular tea consumption was associated with lower risks of cognitive impairment and decline.
Alternative lengthening of telomeres does exist in various canine sarcomas

Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism (TMM) found in some human tumors such as sarcomas. Canine tumors are not characterized for ALT and the study aim was to identify if the ALT phenotype exists in canine sarcomas. Sixty‐four canine sarcoma samples (20 snap‐frozen, 44 FFPE) as well as six canine sarcoma cell lines were screened for ALT by C‐circle assay. ALT was further evaluated by measuring telomere length via qPCR and telomere restriction‐fragments including pulsed‐field electrophoresis. ALT‐associated proteins were validated by immunohistochemistry. Further, telomerase activity (TA) and gene expression were analyzed by TRAP and qPCR. DNA from 20 human neuroblastomas and 8 sarcoma cell lines served as comparative controls. ALT was detected in 9.4% (6/64) canine sarcomas including aggressive subtypes as hemangiosarcoma, osteosarcoma, and histiocytic sarcoma. C‐circle levels were comparable with human ALT‐positive controls. All ALT tumors demonstrated loss of ATRX expression and 5/6 showed strong p53 expression. TA was detected in 93% (14/15) snap‐frozen samples including a sarcoma with ALT activity. This tumor showed long heterogeneous telomeres, and a high level of colocalization of DAXX with telomeres. One sarcoma was ALT and TA negative. All canine and human sarcoma cell lines were ALT negative. In this study, we demonstrated that canine sarcomas use ALT. As in humans, ALT was identified in aggressive sarcomas subtypes and coexisted with TA in one tumor. Overall, canine sarcomas seem to share many similarities with their human counterparts and appear an attractive model for comparative telomere research. © 2016 Wiley Periodicals, Inc.
Non-linear Temporal Subspace Representations for Activity Recognition

Representations that can compactly and effectively capture the temporal evolution of semantic content are important to computer vision and machine learning algorithms that operate on multi-variate time-series data. We investigate such representations motivated by the task of human action recognition. Here each data instance is encoded by a multivariate feature (such as via a deep CNN) where action dynamics are characterized by their variations in time. As these features are often non-linear, we propose a novel pooling method, kernelized rank pooling, that represents a given sequence compactly as the pre-image of the parameters of a hyperplane in a reproducing kernel Hilbert space, projections of data onto which captures their temporal order. We develop this idea further and show that such a pooling scheme can be cast as an order-constrained kernelized PCA objective. We then propose to use the parameters of a kernelized low-rank feature subspace as the representation of the sequences. We cast our formulation as an optimization problem on generalized Grassmann manifolds and then solve it efficiently using Riemannian optimization techniques. We present experiments on several action recognition datasets using diverse feature modalities and demonstrate state-of-the-art results.
Evaluation of a vision-based tactile sensor

Humans can perceive not only the magnitude but also the direction of force applied on the fingertip. When we grasp an object, the weight of it is felt through force that is parallel to the skin of the fingertip, which is how the object can be grasped without slipping. Focusing on this point, we have developed a tactile sensor that can measure a distribution of force vectors. The measurement method is as follows. The tactile sensor consists of a transparent elastic body, blue and red markers inside the elastic body, and a color CCD camera. An applied force on the elastic body results in movements of the markers, which are acquired by the CCD camera. The distribution of force vectors is calculated using this information. This paper reports experimental evaluation results concerning accuracy of determining position of markers, determination of magnitude and direction of force, spatial resolution, and calculation timing.
Human VEGF gene expression in skeletal muscle: effect of acute normoxic and hypoxic exercise.

Vascular endothelial growth factor (VEGF) is involved in extracellular matrix changes and endothelial cell proliferation, both of which are precursors to new capillary growth. Angiogenesis is a vital adaptation to exercise training, and the exercise-induced reduction in intracellular[Formula: see text] has been proposed as a stimulus for this process. Thus we studied muscle cell[Formula: see text] [myoglobin[Formula: see text]([Formula: see text])] during exercise in normoxia and in hypoxia (12% O2) and studied the mRNA levels of VEGF in six untrained subjects after a single bout of exercise by quantitative Northern analysis. Single-leg knee extension provided the acute exercise stimulus: a maximal test followed by 30 min at 50% of the peak work rate achieved in this graded test. Because peak work rate was not affected by hypoxia, the absolute and relative work rates were identical in hypoxia and normoxia. Three pericutaneous needle biopsies were collected from the vastus lateralis muscle, one at rest and then the others at 1 h after exercise in normoxia or hypoxia. At rest (control), VEGF mRNA levels were very low (0.38 ± 0.04 VEGF/18S). After exercise in normoxia or hypoxia, VEGF mRNA levels were much greater (16.9 ± 6.7 or 7.1 ± 1.8 VEGF/18S, respectively). In contrast, there was no measurable basic fibroblast growth factor mRNA response to exercise at this 1-h postexercise time point. Magnetic resonance spectroscopy of myoglobin confirmed a reduction in[Formula: see text] in hypoxia (3.8 ± 0.3 mmHg) compared with normoxia (7.2 ± 0.6 mmHg) but failed to reveal a relationship between [Formula: see text] during exercise and VEGF expression. This VEGF mRNA increase in response to acute exercise supports the concept that VEGF is involved in exercise-induced skeletal muscle angiogenesis but questions the importance of a reduced cellular [Formula: see text]as a stimulus for this response.
The wrong end of the telescope: neuromuscular mimics of movement disorders (and vice versa)

The rapid advances in modern neurology have led to increased specialisation in clinical practice. Being an expert in a neurology subspecialty offers advantages for diagnosing and managing specific disorders. However, specialisation also risks tunnel vision: interpreting symptoms and signs within one's own framework of reference, while ignoring differential diagnostic options from other subspecialties. This is particularly relevant when the patient's presentation potentially belongs to different neurological subspecialties. We illustrate this challenge by highlighting a series of clinical features that partially overlap between two common subspecialties: movement disorders and neuromuscular disorders. An overlap in clinical presentation is not rare, and includes, for example, involuntary eyelid closure (which could be active eye closure due to blepharospasm, or ptosis due to weakness). Other overlapping features include abnormal postures, involuntary movements and gait changes. We describe two of these overlapping features in more detail and emphasise the possible consequences of ‘looking through the wrong end of the telescope’ in such patients, as this may lead to a wrong differential diagnosis, unnecessary investigations and a delayed treatment start.
Homocysteine concentrations in adults with trisomy 21: effect of B vitamins and genetic polymorphisms.

BACKGROUND The effects of supplementation with B vitamins and of common polymorphisms in genes involved in homocysteine metabolism on plasma total homocysteine (tHcy) concentrations in trisomy 21 are unknown. OBJECTIVES We aimed to determine the effects of orally administered folic acid and of folic acid combined with vitamin B-12, vitamin B-6, or both on tHcy in adults with trisomy 21. The study was also intended to analyze the possible influence of gene polymorphisms. DESIGN One hundred sixty adults with trisomy 21 and 160 healthy, unrelated subjects aged 26 +/- 4 y were included. Plasma tHcy, red blood cell folate, serum folate, and vitamin B-12 were measured. Genotyping for the common methylenetetrahydrofolate reductase (MTHFR) 677C-->T, MTHFR 1298A-->C, cystathionine beta-synthase 844Ins68, methionine synthase 2756A-->C, methionine synthase reductase 66A-->G, and reduced folate carrier 80G-->A polymorphisms was carried out. RESULTS The mean tHcy concentration (9.8 +/- 0.7 micromol/L) of cases who did not use vitamins was not significantly different from that of controls (9.4 +/- 0.3 micromol/L). Plasma tHcy concentrations (7.6 +/- 0.3 mmol/L) in cases who used folic acid were significantly lower than in cases who did not. Folic acid combined with vitamin B-12 did not significantly change tHcy concentrations compared with those in cases who used only folic acid. Folic acid combined with vitamins B-6 and B-12 significantly lowered tHcy (6.5 +/- 0.5 micromol/L). The difference in tHcy according to MTHFR genotype was not significant. However, tHcy concentrations were slightly higher in TT homozygotes among the controls but not among the cases. CONCLUSION This study provides information on the relation between several polymorphisms in genes involved in homocysteine and folate metabolism in adults with trisomy 21.
Infant growth patterns in the slums of Dhaka in relation to birth weight, intrauterine growth retardation, and prematurity.

BACKGROUND Relations between size and maturity at birth and infant growth have been studied inadequately in Bangladesh, where the incidence of low birth weight is high and most infants are breast-fed. OBJECTIVE This study was conducted to describe infant growth patterns and their relations to birth weight, intrauterine growth retardation, and prematurity. DESIGN A total of 1654 infants born in selected low-socioeconomic areas of Dhaka, Bangladesh, were enrolled at birth. Weight and length were measured at birth and at 1, 3, 6, 9, and 12 mo of age. RESULTS The infants' mean birth weight was 2516 g, with 46.4% weighing <2500 g; 70% were small for gestational age (SGA) and 17% were premature. Among the SGA infants, 63% had adequate ponderal indexes. The mean weight of the study infants closely tracked the -2 SD curve of the World Health Organization pooled breast-fed sample. Weight differences by birth weight, SGA, or preterm categories were retained throughout infancy. Mean z scores based on the pooled breast-fed sample were -2.38, -1. 72, and -2.34 at birth, 3 mo, and 12 mo. Correlation analysis showed greater plasticity of growth in the first 3 mo of life than later in the first year. CONCLUSIONS Infant growth rates were similar to those observed among breast-fed infants in developed countries. Most study infants experienced chronic intrauterine undernourishment. Catch-up growth was limited and weight at 12 mo was largely a function of weight at birth. Improvement of birth weight is likely to lead to significant gains in infant nutritional status in this population, although interventions in the first 3 mo are also likely to be beneficial.
Radiomics and radiogenomics for precision radiotherapy

Abstract Imaging plays an important role in the diagnosis and staging of cancer, as well as in radiation treatment planning and evaluation of therapeutic response. Recently, there has been significant interest in extracting quantitative information from clinical standard-of-care images, i.e. radiomics, in order to provide a more comprehensive characterization of image phenotypes of the tumor. A number of studies have demonstrated that a deeper radiomic analysis can reveal novel image features that could provide useful diagnostic, prognostic or predictive information, improving upon currently used imaging metrics such as tumor size and volume. Furthermore, these imaging-derived phenotypes can be linked with genomic data, i.e. radiogenomics, in order to understand their biological underpinnings or further improve the prediction accuracy of clinical outcomes. In this article, we will provide an overview of radiomics and radiogenomics, including their rationale, technical and clinical aspects. We will also present some examples of the current results and some emerging paradigms in radiomics and radiogenomics for clinical oncology, with a focus on potential applications in radiotherapy. Finally, we will highlight the challenges in the field and suggest possible future directions in radiomics to maximize its potential impact on precision radiotherapy.