Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediagnostic Calcium Intake and Lung Cancer Survival: A Pooled Analysis of 12 Cohort Studies

Background: Lung cancer is the leading cause of cancer death. Little is known about whether prediagnostic nutritional factors may affect survival. We examined the associations of prediagnostic calcium intake from foods and/or supplements with lung cancer survival. Methods: The present analysis included 23,882 incident, primary lung cancer patients from 12 prospective cohort studies. Dietary calcium intake was assessed using food-frequency questionnaires at baseline in each cohort and standardized to caloric intake of 2,000 kcal/d for women and 2,500 kcal/d for men. Stratified, multivariable-adjusted Cox regression was applied to compute hazard ratios (HR) and 95% confidence intervals (CI). Results: The 5-year survival rates were 56%, 21%, and 5.7% for localized, regional, and distant stage lung cancer, respectively. Low prediagnostic dietary calcium intake (<500–600 mg/d, less than half of the recommendation) was associated with a small increase in risk of death compared with recommended calcium intakes (800–1,200 mg/d); HR (95% CI) was 1.07 (1.01–1.13) after adjusting for age, stage, histology, grade, smoking status, pack-years, and other potential prognostic factors. The association between low calcium intake and higher lung cancer mortality was evident primarily among localized/regional stage patients, with HR (95% CI) of 1.15 (1.04–1.27). No association was found for supplemental calcium with survival in the multivariable-adjusted model. Conclusions: This large pooled analysis is the first, to our knowledge, to indicate that low prediagnostic dietary calcium intake may be associated with poorer survival among early-stage lung cancer patients. Impact: This multinational prospective study linked low calcium intake to lung cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(7); 1060–70. ©2017 AACR.
GnRHa Treatment of Cryptorchid Boys Affects Genes Involved in Hormonal Control of the HPG Axis and Fertility

The gonadotropin-releasing hormone agonist (GnRHa; Buserelin) rescues fertility during adulthood in the majority of high infertility risk cryptorchid boys presenting with defective mini-puberty. However, the molecular events governing this effect are not understood. We report the outcome of an RNA profiling analysis of testicular biopsies from 4 operated patients who were treated with GnRHa for 6 months versus 3 operated controls who were not treated. GnRHa induces a significant transcriptional response, including protein-coding genes involved in pituitary development, the hypothalamic-pituitary-gonadal axis, and testosterone synthesis. Furthermore, we observed an increased abundance of long noncoding RNAs (lncRNAs) participating in epigenetic processes, including AIRN, FENDRR, XIST, and HOTAIR. These data are consistent with the hypothesis that hypogonadotropic hypogonadism in boys with altered mini-puberty is the consequence of a profoundly altered gene expression program involving protein-coding genes and lncRNAs. Our results point to molecular mechanisms that underlie the ability of GnRHa to rescue fertility.
PATHway I: design and rationale for the investigation of the feasibility, clinical effectiveness and cost-effectiveness of a technology-enabled cardiac rehabilitation platform

Introduction Exercise-based cardiac rehabilitation (CR) independently alters the clinical course of cardiovascular diseases resulting in a significant reduction in all-cause and cardiac mortality. However, only 15%–30% of all eligible patients participate in a phase 2 ambulatory programme. The uptake rate of community-based programmes following phase 2 CR and adherence to long-term exercise is extremely poor. Newer care models, involving telerehabilitation programmes that are delivered remotely, show considerable promise for increasing adherence. In this view, the PATHway (Physical Activity Towards Health) platform was developed and now needs to be evaluated in terms of its feasibility and clinical efficacy. Methods and analysis In a multicentre randomised controlled pilot trial, 120 participants (m/f, age 40–80 years) completing a phase 2 ambulatory CR programme will be randomised on a 1:1 basis to PATHway or usual care. PATHway involves a comprehensive, internet-enabled, sensor-based home CR platform and provides individualised heart rate monitored exercise programmes (exerclasses and exergames) as the basis on which to provide a personalised lifestyle intervention programme. The control group will receive usual care. Study outcomes will be assessed at baseline, 3 months and 6 months after completion of phase 2 of the CR programme. The primary outcome is the change in active energy expenditure. Secondary outcomes include cardiopulmonary endurance capacity, muscle strength, body composition, cardiovascular risk factors, peripheral endothelial vascular function, patient satisfaction, health-related quality of life (HRQoL), well-being, mediators of behaviour change and safety. HRQoL and healthcare costs will be taken into account in cost-effectiveness evaluation. Ethics and dissemination The study will be conducted in accordance with the Declaration of Helsinki. This protocol has been approved by the director and clinical director of the PATHway study and by the ethical committee of each participating site. Results will be disseminated via peer-reviewed scientific journals and presentations at congresses and events. Trial registration number NCT02717806. This trial is currently in the pre-results stage.
Microstructure and mechanical properties of NiAl–Cr(Mo)–Hf/Ho near-eutectic alloy prepared by suction casting

Abstract The microstructure and mechanical properties of 0.15 at. % Hf and 0.2 at. % Ho doped Ni-33Al-28Cr-6Mo near-eutectic alloys prepared by conventional casting and suction casting were investigated. The results reveal that the addition of Hf and Ho results in the formation of Ni2AlHf and Ni2Al3Ho phases, respectively, along the NiAl and Cr(Mo) phase interface in intercellular regions. Compared with the conventional-cast alloy, the microstructure of suction-cast alloy is well optimized, characterized by the thin interlamellar spacing, high proportion of eutectic cell area and fine homogeneously distributed Ni2AlHf and Ni2Al3Ho phases. Furthermore, the room temperature mechanical properties of the suction-cast alloy improve significantly, which can be attributed to fine microstructure, uniform distribution of the Ni2AlHf and Ni2Al3Ho phases and solid solubility extension.
Estrogen receptor α wields treatment-specific enhancers between morphologically similar endometrial tumors

Significance This study shows that the hormonal environment in which a tumor originates may affect a hormone receptor’s enhancer usage. We further show that enhancer function is less tissue specific than previously thought. By implementing ChIP sequencing in a unique patient cohort, we compared estrogen receptor α (ERα) profiles in endometrial tumors that developed in different hormonal environments and integrated these comparisons with transcriptomic data. Our data show that tumors associated with therapeutic intervention have a distinct ERα DNA-binding signature with regulatory potentials that resemble ERα-binding patterns in breast cancer. These results highlight the value of cistromic analyses in clinical specimens, which enabled us to distinguish subtypes of tumors on the level of transcriptional regulation. The DNA-binding sites of estrogen receptor α (ERα) show great plasticity under the control of hormones and endocrine therapy. Tamoxifen is a widely applied therapy in breast cancer that affects ERα interactions with coregulators and shifts the DNA-binding signature of ERα upon prolonged exposure in breast cancer. Although tamoxifen inhibits the progression of breast cancer, it increases the risk of endometrial cancer in postmenopausal women. We therefore asked whether the DNA-binding signature of ERα differs between endometrial tumors that arise in the presence or absence of tamoxifen, indicating divergent enhancer activity for tumors that develop in different endocrine milieus. Using ChIP sequencing (ChIP-seq), we compared the ERα profiles of 10 endometrial tumors from tamoxifen users with those of six endometrial tumors from nonusers and integrated these results with the transcriptomic data of 47 endometrial tumors from tamoxifen users and 64 endometrial tumors from nonusers. The ERα-binding sites in tamoxifen-associated endometrial tumors differed from those in the tumors from nonusers and had distinct underlying DNA sequences and divergent enhancer activity as marked by histone 3 containing the acetylated lysine 27 (H3K27ac). Because tamoxifen acts as an agonist in the postmenopausal endometrium, similar to estrogen in the breast, we compared ERα sites in tamoxifen-associated endometrial cancers with publicly available ERα ChIP-seq data in breast tumors and found a striking resemblance in the ERα patterns of the two tissue types. Our study highlights the divergence between endometrial tumors that arise in different hormonal conditions and shows that ERα enhancer use in human cancer differs in the presence of nonphysiological endocrine stimuli.
Folic acid-conjugated polyethylene glycol-coated magnetic nanoparticles for doxorubicin delivery in cancer chemotherapy: Preparation, characterization and cytotoxicity on HeLa cell line

Conventional chemotherapy is the most valid method to cope with cancer; however, it has serious drawbacks such as decrease in production of blood cells or inflammation of the lining of the digestive tract. These side effects occur since generally the drugs used in chemotherapy are distributed evenly within the body of the patient and cannot distinguish the cancer cells from the healthy ones. In this study, folic acid (FA)-conjugated, polyethylene-coated magnetic nanoparticles (FA-MNPs), and doxorubicin (Dox)-loaded formulation (Dox-FA-MNPs) were prepared. The cytotoxicity of these nanoparticles on HeLa and Dox-resistant HeLa cells was investigated. Magnetic nanoparticles (MNPs), polyethylene glycol (PEG)-coated MNPs (PEG-MNPs), and FA-MNPs were successfully synthesized and characterized by several methods. Dox loading of FA-MNPs and release profile of Dox from the nanoparticles were studied. Cytotoxic effects of FA-MNPs and Dox-FA-MNPs on HeLa cells were analyzed. MNPs, PEG-MNPs, and FA-MNPs all had small sizes and supermagnetic behavior. High amounts of Dox could be loded onto the nanoparticles (290 μgmL−1). In 24 h, 15.7% of Dox was released from the Dox-FA-MNPs. The release was increased in acidic conditions (pH 4.1). Internalization studies showed that FA-MNPs and Dox-FA-MNPs were taken up efficiently by HeLa cells. The investigation of cytotoxicity of the particles indicated that 38–500 μgmL−1 Dox-FA-MNPs significantly decreased the proliferation of HeLa cells compared to FA-MNPs. Due to their size, magnetic properties, internalization, drug release, and cytotoxicity characteristics, the MNPs prepared in this study may have potential application as a drug delivery system in cancer chemotherapy.
Exploring the perceived usefulness of practical food groups in day treatment for individuals with eating disorders

BACKGROUND/AIM Recovery from eating disorders is a challenging process. Emerging literature suggests that occupational therapists may provide a useful contribution in delivering purposeful eating-related interventions as a potential treatment to support sustained cognitive and behavioural changes for individuals with eating disorders. This study aimed to evaluate participants' perceptions of the contribution of occupational therapy practical food groups (food based outings and cooking groups) in supporting their functional recovery. METHODS Individuals attended practical food groups as part of standard treatment at an outpatient eating disorders day program. Ninety-nine participants completed questionnaires at discharge and up to three follow-up points (6, 12 and 24 months). Questions related to practical food groups were analysed, exploring participants' experiences and perceived usefulness of groups using rating-scale and open-ended questions. Open-ended responses were analysed using thematic analysis. Descriptive statistics were calculated for responses to rating-scale questions. RESULTS At discharge, participants rated the importance and usefulness of practical food groups as high (4.73 and 4.43 on 5-point scales, respectively), but tended to rate their enjoyment of the groups lower (3.50 on a 5-point scale). Some skill transfer was typically reported by participants at discharge (3.92 on a 5-point scale). One core theme, 'success through participation', emerged from qualitative comments. Six subthemes were also identified: helpful components of practical food groups; perceived benefit of exposure; impact of applying cognitive and behavioural skills; challenges affecting participation; facilitating adaptation; and influence of eating disorders on challenging feared foods. CONCLUSION This study highlights that participation in practical food groups was perceived as useful in assisting individuals to improve eating behaviours and, in some circumstances, transfer these skills into their lives outside of day program. Results suggest that occupational therapists may have an important contribution in delivering these interventions to support recovery and facilitate application of adaptive coping strategies.
Estimating High-dimensional Non-Gaussian Multiple Index Models via Stein's Lemma

We consider estimating the parametric components of semiparametric multi-index models in high dimensions. To bypass the requirements of Gaussianity or elliptical symmetry of covariates in existing methods, we propose to leverage a second-order Stein’s method with score function-based corrections. We prove that our estimator achieves a near-optimal statistical rate of convergence even when the score function or the response variable is heavy-tailed. To establish the key concentration results, we develop a data-driven truncation argument that may be of independent interest. We supplement our theoretical findings with simulations.
B and T lymphocyte attenuator inhibits LPS-induced endotoxic shock by suppressing Toll-like receptor 4 signaling in innate immune cells

Although innate immune responses are necessary for the initiation of acquired immune responses and the subsequent successful elimination of pathogens, excessive responses occasionally result in lethal endotoxic shock accompanied by a cytokine storm. B and T lymphocyte attenuator (BTLA), a coinhibitory receptor with similarities to cytotoxic T-lymphocyte antigen (CTLA)-4 and programmed death (PD)-1, is expressed in not only B and T cells but also dendritic cells (DCs) and macrophages (Mϕs). Recently, several studies have reported that BTLA-deficient (BTLA−/−) mice show enhanced pathogen clearance compared with WT mice in early phase of infections. However, the roles of BTLA expressed on innate cells in overwhelming and uncontrolled immune responses remain unclear. Here, we found that BTLA−/− mice were highly susceptible to LPS-induced endotoxic shock. LPS-induced TNF-α and IL-12 production in DCs and Mϕs was significantly enhanced in BTLA−/− mice. BTLA−/− DCs also produced high levels of TNF-α on stimulation with Pam3CSK4 but not poly(I:C) or CpG, suggesting that BTLA functions as an inhibitory molecule on Toll-like receptor signaling at cell surface but not endosome. Moreover, BTLA−/− DCs showed enhanced MyD88- and toll/IL-1R domain-containing adaptor inducing IFN (TRIF)-dependent signaling on LPS stimulation, which is associated with impaired accumulation of Src homology 2-containing protein tyrosine phosphatase in lipid rafts. Finally, we found that an agonistic anti-BTLA antibody rescued mice from LPS-induced endotoxic shock, even if the antibody was given to mice that had developed a sign of endotoxic shock. These results suggest that BTLA directly inhibits LPS responses in DCs and Mϕs and that agonistic agents for BTLA might have therapeutic potential for LPS-induced endotoxic shock.
Linear Data Compression of Hyperspectral Images

The aim of the paper is to analyse hyperspectral images using tensor principal component analysis of multi-way data sets. The mathematical and computational backgrounds of pattern recognition are the geometries in Hilbert space for functional analysis and applied linear algebra for numerical analysis, respectively. Because of high-resolution sampling in the colour channels, images observed by a hyperspectral camera system are expressed by three-mode tensors. The Tucker-3 decomposition of a three-mode tensor is used in behaviourmetric science and psychology for the extraction of relations among three entries as an extension of the usual principal component analysis for statistical analysis. Hyperspectral images express spectral information of two-dimensional images on the imaging plane. Therefore, for statistical analysis, we adopt the Tucker-3 decomposition. The Tucker-3 decomposition of hyperspectral images extracts statistically dominant information from hyperspectral images. Tensor principal component analysis allows us to extract dominant light-channel information from hyperspectral images.
Incidence of diabetes-related complications in Chinese patients with type 1 diabetes: a population-based longitudinal cohort study in Taiwan

Objective To estimate the incidence densities and cumulative incidence of diabetes-related complications in patients with type 1 diabetes for a maximum of 15-year follow-up. The estimations were further stratified by gender and age at diagnosis (ie, early onset: 0–12 years, late onset:≥13 years). Design A population-based retrospective longitudinal cohort study. Setting Taiwan’s National Health Insurance medical claims. Participants 4007 patients newly diagnosed with type 1 diabetes were identified during 1999–2012. Outcome measures Acute complications included diabetic ketoacidosis (DKA) and hypoglycaemia. Chronic complications were cardiovascular diseases (CVD), retinopathy, neuropathy and nephropathy. Results The incidence density of retinopathy was greatest (97.74 per 1000 person-years), followed by those of nephropathy (31.36), neuropathy (23.93) and CVD (4.39). Among acute complications, the incidence density of DKA was greatest (121.11 per 1000 person-years). The cumulative incidences of acute complications after 12 years following diagnosis were estimated to be 52.1%, 36.1% and 4.1% for DKA, outpatient hypoglycaemia and hospitalised hypoglycaemia, respectively. For chronic complications, the cumulative incidence of retinopathy after 12 years following diagnosis was greatest (65.2%), followed by those of nephropathy (30.2%), neuropathy (23.7%) and CVD (4.1%). Females with late-onset diabetes were greatly affected by advanced retinopathy (ie, sight-threatening diabetic retinopathy) and hospitalised hypoglycaemia, whereas those with early-onset diabetes were more vulnerable to DKA. Chronic complications were more commonly seen in late-onset diabetes, whereas early-onset diabetes were most affected by acute complications. Conclusions Ethnic Chinese patients with type 1 diabetes were greatly affected by DKA and retinopathy. The incidence of diabetes-related complications differed by age at diagnosis and sex.
The Interventional Effect of Remote Ischemic Preconditioning on Cerebral Small Vessel Disease: A Pilot Randomized Clinical Trial

Background: Remote ischemic preconditioning (RIPC) of the limb has been shown to induce ischemic tolerance in basic and clinical studies that focused on sustained large artery occlusion rather than small vessel disease (SVD). This study aimed to evaluate the protective effects of brief repetitive limb RIPC on patients with cerebral SVD. Methods: Seventeen patients with cerebral SVD were enrolled. Patients underwent 5 ischemia-reperfusion cycles of preconditioning/sham preconditioning on both upper limbs twice a day for 1 year. Cerebral hemodynamic indexes, brain lesions, cognitive functions and assessment outcomes of dizziness handicap inventory (DHI) were analyzed. Results: In the RIPC group, the mean flow velocity (MFV) of the left middle cerebral artery (MCA) was accelerated (57.33 (52.33-61.34) vs. 51.33 (48.83-58.33), respectively; p = 0.038), and the post-treatment DHI score was reduced (18 (13-19) vs. 34 (21-45), respectively; p = 0.043). The post-treatment volume of the white matter lesions (WMLs) was also reduced (4.19 (2.96-7.25) vs. 6.06 (4.67-10.95), respectively; p = 0.050). There was no remarkable difference between the 2 groups either before or after treatment. Conclusion: The present study indicates that RIPC has potential beneficial effects on cerebral SVD by increasing the MFV of MCA, decreasing the DHI score as well as the volume of WMLs in patients with SVD.
ILEX: an architecture for a dynamic hypertext generation system

Generating text in a hypermedia environment places different demands on a text generation system than occurs in non-interactive environments. This paper describes some of these demands, then shows how the architecture of one text generation system, ILEX, has been shaped by them. The architecture is described in terms of the levels of linguistic representation used, and the processes which map between them. Particular attention is paid to the processes of content selection and text structuring.
Use of Reverse Vaccinology in the Design and Construction of Nanoglycoconjugate Vaccines against Burkholderia pseudomallei

ABSTRACT Burkholderia pseudomallei is a Gram-negative, facultative intracellular pathogen that causes the disease melioidosis in humans and other mammals. Respiratory infection with B. pseudomallei leads to a fulminant and often fatal disease. It has previously been shown that glycoconjugate vaccines can provide significant protection against lethal challenge; however, the limited number of known Burkholderia antigens has slowed progress toward vaccine development. The objective of this study was to identify novel antigens and evaluate their protective capacity when incorporated into a nanoglycoconjugate vaccine platform. First, an in silico approach to identify antigens with strong predicted immunogenicity was developed. Protein candidates were screened and ranked according to predicted subcellular localization, transmembrane domains, adhesive properties, and ability to interact with major histocompatibility complex (MHC) class I and class II. From these in silico predictions, we identified seven “high priority” proteins that demonstrated seroreactivity with anti-B. pseudomallei murine sera and convalescent human melioidosis sera, providing validation of our methods. Two novel proteins, together with Hcp1, were linked to lipopolysaccharide (LPS) and incorporated with the surface of a gold nanoparticle (AuNP). Animals receiving AuNP glycoconjugate vaccines generated high protein- and polysaccharide-specific antibody titers. Importantly, immunized animals receiving the AuNP-FlgL-LPS alone or as a combination demonstrated up to 100% survival and reduced lung colonization following a lethal challenge with B. pseudomallei. Together, this study provides a rational approach to vaccine design that can be adapted for other complex pathogens and provides a rationale for further preclinical testing of AuNP glycoconjugate in animal models of infection.