Miracle-dz/UniFAR-FTUs huggingface dataset:
Palliative Care in the Global Setting: ASCO Resource-Stratified Practice Guideline

Purpose The purpose of this new resource-stratified guideline is to provide expert guidance to clinicians and policymakers on implementing palliative care of patients with cancer and their caregivers in resource-constrained settings and is intended to complement the Integration of Palliative Care Into Standard Oncology Care: American Society of Clinical Oncology Clinical Practice Guideline Update of 2016. Methods ASCO convened a multidisciplinary, multinational panel of experts in medical oncology, family medicine, radiation oncology, hematology/oncology, palliative and/or hospice care, pain and/or symptom management, patient advocacy, public health, and health economics. Guideline development involved a systematic literature review, a modified ADAPTE process, and a formal consensus-based process with the Expert Panel and additional experts (consensus ratings group). Results The systematic review included 48 full-text publications regarding palliative care in resource-constrained settings, along with cost-effectiveness analyses; the evidence for many clinical questions was limited. These provided indirect evidence to inform the formal consensus process, which resulted in agreement of ≥ 75% (by consensus ratings group including Expert Panel). Recommendations The recommendations help define the models of care, staffing requirements, and roles and training needs of team members in a variety of resource settings for palliative care. Recommendations also outline the standards for provision of psychosocial support, spiritual care, and opioid analgesics, which can be particularly challenging and often overlooked in resource-constrained settings. Additional information is available at www.asco. org/resource-stratified-guidelines. It is the view of ASCO that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.
Fatigue is not associated with vitamin D deficiency in inflammatory bowel disease patients

AIM To investigate if vitamin D deficiency is associated with fatigue in patients with inflammatory bowel disease (IBD). METHODS IBD patients were recruited from nine hospitals in the southeastern and western regions of Norway to participate in a multicenter cross-sectional study lasting from March 2013 to April 2014. Data were collected by interviews, from medical records and laboratory tests. The Fatigue Questionnaire (FQ) was used to measure fatigue. Linear and logistic regression models were applied to explore the possible association between vitamin D deficiency and total fatigue scores and chronic fatigue, respectively. The analyses were adjusted for age, gender, disease activity, depressive symptoms and sleep disturbance. RESULTS In total, 405 patients were included in the analyses, of which 227 (56%) had Crohn’s disease (CD) and 178 (44%) had ulcerative colitis (UC). Vitamin D deficiency (< 50 nmol/L) was present in half (203/405) of the patients. Chronic fatigue was reported by 116 (29%) of all included patients with substantial fatigue reported by 194 (48%). Vitamin D levels were neither associated with total fatigue nor with chronic fatigue. Higher total fatigue scores and chronic fatigue were both associated with increased disease activity scores in patients with UC and CD, but not with increased CRP or fecal calprotectin. In UC patients, female gender was associated with fatigue in the univariate analysis, but no such difference was found when adjusted for elevated disease activity scores. Sleep disturbance and more depressive symptoms were associated with total fatigue scores in both UC and CD patients, but with chronic fatigue only in CD patients. CONCLUSION In this study, no significant association between fatigue and vitamin D deficiency in IBD patients was revealed.
From Knowledge Graph Embedding to Ontology Embedding? An Analysis of the Compatibility between Vector Space Representations and Rules

Recent years have witnessed the successful application of low-dimensional vector space representations of knowledge graphs to predict missing facts or find erroneous ones. However, it is not yet well-understood to what extent ontological knowledge, e.g. given as a set of (existential) rules, can be embedded in a principled way. To address this shortcoming, in this paper we introduce a general framework based on a view of relations as regions, which allows us to study the compatibility between ontological knowledge and different types of vector space embeddings. Our technical contribution is two-fold. First, we show that some of the most popular existing embedding methods are not capable of modelling even very simple types of rules, which in particular also means that they are not able to learn the type of dependencies captured by such rules. Second, we study a model in which relations are modelled as convex regions. We show particular that ontologies which are expressed using so-called quasi-chained existential rules can be exactly represented using convex regions, such that any set of facts which is induced using that vector space embedding is logically consistent and deductively closed with respect to the input ontology.
Dietary Carotenoids Intake and the Risk of Gastric Cancer: A Case—Control Study in Korea

Although the incidence of gastric cancer (GC) has declined, it remains the second most common cancer in Korea. As a class of phytochemicals, carotenoids are fat-soluble pigments that are abundant in fruits and vegetables and have health-promoting properties, including cancer prevention effects. This case-control study investigated the effects of total dietary carotenoids, dietary carotenoid subclasses (α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin, and lycopene), and foods contributing to the dietary intake of each carotenoid on the risk of GC. Four hundred and fifteen cases and 830 controls were recruited from the National Cancer Center Hospital in Korea between March 2011 and December 2014. A significant inverse association between total dietary carotenoids and GC risk was observed among women (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.32–0.99). A higher intake of dietary lycopene was inversely associated with GC risk overall in the subjects (OR 0.60, 95% CI 0.42–0.85, p for trend = 0.012), men (OR 0.60, 95% CI 0.39–0.93), and women (OR 0.54, 95% CI 0.30–0.96, p for trend = 0.039). This significant association between dietary lycopene intake and GC risk was also observed in the subgroups of Helicobacter pylori (H. pylori)-positive subjects and those who had ever smoked. Among the major contributing foods of dietary lycopene, consumption of tomatoes and tomato ketchup was inversely associated with GC risk in the overall subjects, men, and women. Based on our findings, a higher intake of dietary lycopene and contributing foods of lycopene (tomatoes and tomato ketchup) may be inversely associated with the risk of GC.
Power Constrained Parallel Queuing with Contention

We examine deterministic broadcasting on multiple-access channels for a scenario when packets are injected continuously by an adversary to the buffers of the devices at rate $\rho$ packages per round. The aim is to maintain system stability, that is, bounded queues. In contrast to previous work we assume that there is a strict limit of available power, defined as the total number of stations allowed to transmit or listen to the channel at a given time, that can never be exceeded. We study how this constraint influences the quality of services with particular focus on stability. We show that in the regime of deterministic algorithms, the significance of energy restriction depends strongly on communication capabilities of broadcasting protocols. For the adaptive and full-sensing protocols, wherein stations may substantially adopt their behavior to the injection pattern, one can construct efficient algorithms using very small amounts of power without sacrificing throughput or stability of the system. In particular, we construct constant-energy adaptive and full sensing protocols stable for $\rho=1$ and any $\rho<1$, respectively, even for worst case (adversarial) injection patterns. Surprisingly, for the case of acknowledgment based algorithms that cannot adopt to the situation on the channel (i.e., their transmitting pattern is fixed in advance), limiting power leads to reducing the throughput. That is, for this class of protocols in order to preserve stability we need to reduce injection rate significantly. We support our theoretical analysis by simulation results of algorithms constructed in the paper. We depict how they work for systems of moderate, realistic sizes. We also provide a comprehensive simulation to compare our algorithms with backoff algorithms, which are common in real-world implementations, in terms of queue sizes and energy consumption.
Strain differences in thymic atrophy in rats immunized for EAE correlate with the clinical outcome of immunization

An accumulating body of evidence suggests that development of autoimmune pathologies leads to thymic dysfunction and changes in peripheral T-cell compartment, which, in turn, perpetuate their pathogenesis. To test this hypothesis, thymocyte differentiation/maturation in rats susceptible (Dark Agouti, DA) and relatively resistant (Albino Oxford, AO) to experimental autoimmune encephalomyelitis (EAE) induction was examined. Irrespective of strain, immunization for EAE (i) increased the circulating levels of IL-6, a cytokine causally linked with thymic atrophy, and (ii) led to thymic atrophy reflecting partly enhanced thymocyte apoptosis associated with downregulated thymic IL-7 expression. Additionally, immunization diminished the expression of Thy-1, a negative regulator of TCRαβ-mediated signaling and activation thresholds, on CD4+CD8+ TCRαβlo/hi thymocytes undergoing selection and thereby impaired thymocyte selection/survival. This diminished the generation of mature CD4+ and CD8+ single positive TCRαβhi thymocytes and, consequently, CD4+ and CD8+ recent thymic emigrants. In immunized rats, thymic differentiation of natural regulatory CD4+Foxp3+CD25+ T cells (nTregs) was particularly affected reflecting a diminished expression of IL-7, IL-2 and IL-15. The decline in the overall thymic T-cell output and nTreg generation was more pronounced in DA than AO rats. Additionally, differently from immunized AO rats, in DA ones the frequency of CD28- cells secreting cytolytic enzymes within peripheral blood CD4+ T lymphocytes increased, as a consequence of thymic atrophy-related replicative stress (mirrored in CD4+ cell memory pool expansion and p16INK4a accumulation). The higher circulating level of TNF-α in DA compared with AO rats could also contribute to this difference. Consistently, higher frequency of cytolytic CD4+ granzyme B+ cells (associated with greater tissue damage) was found in spinal cord of immunized DA rats compared with their AO counterparts. In conclusion, the study indicated that strain differences in immunization-induced changes in thymopoiesis and peripheral CD4+CD28- T-cell generation could contribute to rat strain-specific clinical outcomes of immunization for EAE.
Searching for novel biomarkers using a mouse model of CLN3-Batten disease

CLN3-Batten disease is a rare, autosomal recessive disorder involving seizures, visual, motor and cognitive decline, and premature death. The Cln3Δex7/8 mouse model recapitulates several phenotypic characteristics of the most common 1.02kb disease-associated deletion. Identification of reproducible biomarker(s) to facilitate longitudinal monitoring of disease progression and provide readouts for therapeutic response has remained elusive. One factor that has complicated the identification of suitable biomarkers in this mouse model has been that variations in animal husbandry appear to significantly influence readouts. In the current study, we cross-compared a number of biological parameters in blood from Cln3Δex7/8 mice and control, non-disease mice on the same genetic background from multiple animal facilities in an attempt to better define a surrogate marker of CLN3-Batten disease. Interestingly, we found that significant differences between Batten and non-disease mice found at one site were generally not maintained across different facilities. Our results suggest that colony variation in the Cln3Δex7/8 mouse model of CLN3-Batten disease can influence potential biomarkers of the disease.
Parallel Accumulation of Tumor Hyaluronan, Collagen, and Other Drivers of Tumor Progression

Purpose: The tumor microenvironment (TME) evolves to support tumor progression. One marker of more aggressive malignancy is hyaluronan (HA) accumulation. Here, we characterize biological and physical changes associated with HA-accumulating (HA-high) tumors. Experimental Design: We used immunohistochemistry, in vivo imaging of tumor pH, and microdialysis to characterize the TME of HA-high tumors, including tumor vascular structure, hypoxia, tumor perfusion by doxorubicin, pH, content of collagen. and smooth muscle actin (α-SMA). A novel method was developed to measure real-time tumor-associated soluble cytokines and growth factors. We also evaluated biopsies of murine and pancreatic cancer patients to investigate HA and collagen content, important contributors to drug resistance. Results: In immunodeficient and immunocompetent mice, increasing tumor HA content is accompanied by increasing collagen content, vascular collapse, hypoxia, and increased metastatic potential, as reflected by increased α-SMA. In vivo treatment of HA-high tumors with PEGylated recombinant human hyaluronidase (PEGPH20) dramatically reversed these changes and depleted stores of VEGF-A165, suggesting that PEGPH20 may also diminish the angiogenic potential of the TME. Finally, we observed in xenografts and in pancreatic cancer patients a coordinated increase in HA and collagen tumor content. Conclusions: The accumulation of HA in tumors is associated with high tIP, vascular collapse, hypoxia, and drug resistance. These findings may partially explain why more aggressive malignancy is observed in the HA-high phenotype. We have shown that degradation of HA by PEGPH20 partially reverses this phenotype and leads to depletion of tumor-associated VEGF-A165. These results encourage further clinical investigation of PEGPH20. Clin Cancer Res; 24(19); 4798–807. ©2018 AACR.
A comprehensive clinical and genetic study in 127 patients with ID in Kinshasa, DR Congo

Pathogenic variants account for 4 to 41% of patients with intellectual disability (ID) or developmental delay (DD). In Sub‐Saharan Africa, the prevalence of ID is thought to be higher, but data in Central Africa are limited to some case reports. In addition, clinical descriptions of some syndromes are not available for this population. This study aimed at providing an estimate for the fraction of ID/DD for which an underlying etiological genetic cause may be elucidated and provide insights into their clinical presentation in special institutions in a Central African country. A total of 127 patients (33 females and 94 males, mean age 10.03 ± 4.68 years), were recruited from six institutions across Kinshasa. A clinical diagnosis was achieved in 44 but molecular confirmation was achieved in 21 of the 22 patients with expected genetic defect (95% clinical sensitivity). Identified diseases included Down syndrome (15%), submicroscopic copy number variants (9%), aminoacylase deficiency (0.8%), Partington syndrome in one patient (0.8%) and his similarly affected brother, X‐linked syndromic Mental Retardation type 33 (0.8%), and two conditions without clear underlying molecular genetic etiologies (Oculo‐Auriculo‐Vertebral and Amniotic Bands Sequence). We have shown that genetic etiologies, similar to those reported in Caucasian subjects, are a common etiologic cause of ID in African patients from Africa. We have confirmed the diagnostic utility of clinical characterization prior to genetic testing. Finally, our clinical descriptions provide insights into the presentation of these genetic diseases in African patients.
The Effects of Hydration Status on Cognitive Performances among Young Adults in Hebei, China: A Randomized Controlled Trial (RCT)

Background: Dehydration may affect cognitive performances as water accounts for 75% of brain mass. The purpose of this study is to investigate the effects of dehydration and water supplementation on cognitive performances, and to explore the changes of brain structures and functions using MRI. Methods and Analysis: A double-blinded randomized controlled trial has been designed and will be implemented among 64 college students aged 18–23 years from Baoding, China. Subjects will be asked to restrict water for 36 h. The first morning urine will be collected and urine osmolality measured. The fasting blood samples will be collected and osmolality and copeptin will be measured. Three MRI sequences, including fMRI, ASL and 3D BRAVO will be taken to observe the changes of whole brain volume, ventricular volume, BOLD response and the cortex thickness. Cognitive performances and mood will be performed with software and questionnaires, respectively. Subjects in the water supplementation groups 1, 2, 3 will drink 200, 500 and 1000 mL of water, respectively, while subjects in the no water supplementation group will not drink any water. After 90 min, urine and blood samples, MRI scans, cognitive performances and mood will be performed. One-way ANOVA will be used to study the differences among groups. Ethics and Dissemination: The study protocol has been approved by the Peking University Institutional Review Committee. Ethical approval project identification code is IRB00001052-16071. Results will be published according to the CONSORT statement and will be reported in peer-reviewed journals.
Like and share: associations between social media engagement and dietary choices in children

Abstract Objective To examine whether social media and online behaviours are associated with unhealthy food and beverage consumption in children. Design A cross-sectional online survey was used to assess Internet and social media use, including engagement with food and beverage brand content, and frequency of consumption of unhealthy foods and beverages. Linear regression models were used to examine associations between online behaviours, including engagement with food and beverage brand content, and consumption of unhealthy foods and beverages, adjusting for age, sex and socio-economic status. Setting New South Wales, Australia, in 2014. Subjects Children aged 10–16 years (n 417). Results Watching food brand video content on YouTube, purchasing food online and seeing favourite food brands advertised online were significantly associated with higher frequency of consumption of unhealthy foods and drinks after adjustment for age, sex and socio-economic status. Conclusions Children who have higher online engagement with food brands and content, particularly through online video, are more likely to consume unhealthy foods and drinks. Our findings highlight the need to include social media in regulations and policies designed to limit children’s exposure to unhealthy food marketing. Social media companies have a greater role to play in protecting children from advertising.
Optic disc microvasculature dropout in primary open-angle glaucoma measured with optical coherence tomography angiography

Purpose To evaluate microvasculature dropout in the optic disc (Mvd-D) using optical coherence tomography angiography (OCTA) and investigate factors associated with Mvd-D in primary open-angle glaucoma (POAG) eyes. Methods One hundred twenty-three eyes of 123 POAG patients were included from the Diagnostic Innovations in Glaucoma Study. The 3.0×3.0-mm optic nerve head OCTA scans were acquired using a spectral-domain OCT instrument. Images with whole-signal-mode were evaluated. Eyes were classified into 3 categories (Mvd-D, pseudo-Mvd-D, and no Mvd-D). Mvd-D and pseudo-Mvd-D had complete loss of OCTA signals on the temporal side of the optic disc on the en face projection image. They were distinguished base on the visualization of the anterior lamina cribrosa in the horizontal B-scans of that area. No Mvd-D was defined when no complete signal loss of OCTA signals was observed. Covariates including focal lamina cribrosa defects assessed by swept-source OCT and microvasculature dropout in the parapapillary region (Mvd-P) were analyzed. Results Forty-two, 37, and 44 eyes were identified as having Mvd-D, pseudo-Mvd-D, and no Mvd-D, respectively. The eyes with Mvd-D showed significantly lower intraocular pressure, worse visual field mean deviation, larger cup-to-disc ratio, thinner circumpapillary retinal nerve fiber layer (cpRNFL), and lower circumpapillary vessel density within the RNFL than the eyes with pseudo-Mvd-D or the eyes without Mvd-D. Multivariable logistic regression analysis showed significant associations of Mvd-D with larger cup-to-disc ratio (OR, 1.08; P = 0.001), worse visual field mean deviation (OR, 1.09; P = 0.048), higher prevalence of focal lamina cribrosa defect (OR, 9.05; P = 0.002), and higher prevalence of Mvd-P (OR, 10.33; P <0.001). Conclusions OCTA-derived Mvd-D was strongly associated with the presences of Mvd-P and focal lamina cribrosa defects, and these 3 findings were topographically associated with each other.
DUSP6 mediates T cell receptor-engaged glycolysis and restrains TFH cell differentiation

Significance Naive T cells at quiescent state utilize mitochondrial respiration to generate ATP. In response to antigen, activated T cells through T cell receptor (TCR) and CD28 differentiate to TH1, TH2, or TH17 effector cells with an induction of aerobic glycolysis. Here, we demonstrate a role for DUSP6 in the glycolysis commitment during T cell activation. DUSP6 deficiency prompts activated T cells to rely on glucose-independent fuels. We show that DUSP6 fine-tunes TCR-MAPK signaling, which determines follicular helper T (TFH) effector-cell differentiation regardless of a glycolytic defect. Our findings imply that glycolysis is required for survival of activated T cells but optional for IL-21 production in TFH cell differentiation. Activated T cells undergo metabolic reprogramming and effector-cell differentiation but the factors involved are unclear. Utilizing mice lacking DUSP6 (DUSP6−/−), we show that this phosphatase regulates T cell receptor (TCR) signaling to influence follicular helper T (TFH) cell differentiation and T cell metabolism. In vitro, DUSP6−/− CD4+ TFH cells produced elevated IL-21. In vivo, TFH cells were increased in DUSP6−/− mice and in transgenic OTII-DUSP6−/− mice at steady state. After immunization, DUSP6−/− and OTII-DUSP6−/− mice generated more TFH cells and produced more antigen-specific IgG2 than controls. Activated DUSP6−/− T cells showed enhanced JNK and p38 phosphorylation but impaired glycolysis. JNK or p38 inhibitors significantly reduced IL-21 production but did not restore glycolysis. TCR-stimulated DUSP6−/− T cells could not induce phosphofructokinase activity and relied on glucose-independent fueling of mitochondrial respiration. Upon CD28 costimulation, activated DUSP6−/− T cells did not undergo the metabolic commitment to glycolysis pathway to maintain viability. Unexpectedly, inhibition of fatty acid oxidation drastically lowered IL-21 production in DUSP6−/− TFH cells. Our findings suggest that DUSP6 connects TCR signaling to activation-induced metabolic commitment toward glycolysis and restrains TFH cell differentiation via inhibiting IL-21 production.