Miracle-dz/UniFAR-FTUs huggingface dataset:
Trisomy 21 dysregulates T cell lineages toward an autoimmunity-prone state associated with interferon hyperactivity

Significance Triplication of human chromosome 21, or trisomy 21 (T21), causes the condition known as Down syndrome (DS). People with DS show a markedly different disease spectrum relative to typical people, being highly predisposed to conditions such as Alzheimer’s disease, while being protected from other conditions, such as most solid malignancies. Interestingly, people with DS are affected by high rates of autoimmune disorders, whereby the immune system mistakenly attacks healthy tissues. This manuscript reports an exhaustive characterization of the T cells of people with DS, demonstrating many alterations in this key immune cell type that could explain their high risk of autoimmunity. These results reveal opportunities for therapeutic intervention to modulate T cell function and improve health outcomes in DS. Trisomy 21 (T21) causes Down syndrome (DS), a condition characterized by high prevalence of autoimmune disorders. However, the molecular and cellular mechanisms driving this phenotype remain unclear. Building upon our previous finding that T cells from people with DS show increased expression of interferon (IFN)-stimulated genes, we have completed a comprehensive characterization of the peripheral T cell compartment in adults with DS with and without autoimmune conditions. CD8+ T cells from adults with DS are depleted of naïve subsets and enriched for differentiated subsets, express higher levels of markers of activation and senescence (e.g., IFN-γ, Granzyme B, PD-1, KLRG1), and overproduce cytokines tied to autoimmunity (e.g., TNF-α). Conventional CD4+ T cells display increased differentiation, polarization toward the Th1 and Th1/17 states, and overproduction of the autoimmunity-related cytokines IL-17A and IL-22. Plasma cytokine analysis confirms elevation of multiple autoimmunity-related cytokines (e.g., TNF-α, IL17A–D, IL-22) in people with DS, independent of diagnosis of autoimmunity. Although Tregs are more abundant in DS, functional assays show that CD8+ and CD4+ effector T cells with T21 are resistant to Treg-mediated suppression, regardless of Treg karyotype. Transcriptome analysis of white blood cells and T cells reveals strong signatures of T cell differentiation and activation that correlate positively with IFN hyperactivity. Finally, mass cytometry analysis of 8 IFN-inducible phosphoepitopes demonstrates that T cell subsets with T21 show elevated levels of basal IFN signaling and hypersensitivity to IFN-α stimulation. Therefore, these results point to T cell dysregulation associated with IFN hyperactivity as a contributor to autoimmunity in DS.
Wearable Organic Electrochemical Transistor Patch for Multiplexed Sensing of Calcium and Ammonium Ions from Human Perspiration

Wearable health monitoring has garnered considerable interest from the healthcare industry as an evolutionary alternative to standard practices with the ability to provide rapid, off‐site diagnosis and patient‐monitoring. In particular, sweat‐based wearable biosensors offer a noninvasive route to continuously monitor a variety of biomarkers for a range of physiological conditions. Both the accessibility and wealth of information of sweat make it an ideal target for noninvasive devices that can aid in early diagnosis of disease or to monitor athletic performance. Here, the integration of ammonium (NH4+) and calcium (Ca2+) ion‐selective membranes with a poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate)‐based (PEDOT:PSS) organic electrochemical transistor (OECT) for multiplexed sensing of NH4+ and Ca2+ in sweat with high sensitivity and selectivity is reported for the first time. The presented wearable sweat sensor is designed by combining a flexible and stretchable styrene‐ethylene‐butene‐styrene substrate with a laser‐patterned microcapillary channel array for direct sweat acquisition and delivery to the ion‐selective OECT. The resulting dermal sensor exhibits a wide working range between 0.01 × 10−3 and 100 × 10−3 m, well within the physiological levels of NH4+ and Ca2+ in sweat. The integrated devices are successfully implemented with both ex situ measurements and on human subjects with real‐time analysis using a wearable sensor assembly.
A Qualitative Evaluation of the Efficacy of the Delivery of the Educational Component of a Nutrition Program, in a Remote First Nation Community 1

Obesity is disproportionately affecting Aboriginal people in Canada. Physical activity and a healthy diet can help maintain a healthy body weight. We implemented a comprehensive school-based nutrition program in the remote community of Fort Albany First Nation that included these components: 1. health education; 2. healthy environment; 3. healthy policy; 4. community and family involvement; 5. program evaluation. In this paper, we evaluated qualitatively the efficacy of the delivery of the educational component of 1. We would like to thank the community of Fort Albany, Ontario, Canada, for their participation in this research especially the students and staff of Mundo Peetabeck Academy. We would also like to offer our appreciation to Fort Albany Chief & Council, Mundo Peetabeck Education Authority, Dr. Dan McCarthy, Christine Barbeau, Nadia Charania, and especially Joan Metatawabin for all of their support with the program. We thank the Canadian Institutes of Health Research, Canada’s ResearchBased Pharmaceutical Companies Health Research Foundation, and Health Canada’s First Nations and Inuit Health Branch for funding support.
The Frequency and Timing of Recurrent Stroke.

BACKGROUND Stroke is among the leading causes of death in Germany and one of the main reasons for handicap and disability. The risk factors for stroke include hypertension, metabolic disorders, and diabetes. An estimated 250 000 persons sustain a stroke in Germany each year. German data on the occurrence of stroke, and of recurrent stroke in particular, are still inadequate. The main objective of this study was to determine the frequency and timing of recurrent stroke. METHODS The analyses were based on routine data of the AOK statutory health insurance fund in the German federal state of Lower Saxony. Inpatient billing and diagnosis data were used to identify initial and recurrent strokes (ICD-10 I60-I64). The derived incidence and prevalence were standardized for age and sex. The risks of recurrence and mortality were estimated with Kaplan-Meier analyses and Cox regressions. RESULTS In 2010/2011, the standardized incidence of stroke was 292 per 100 000 persons per year, and the standardized prevalence was 336 per 100 000 persons. The risk of recurrence was 1.2% in the first 30 days, 3.4% within 90 days, 7.4% within 1 year, and 19.4% within 5 years. The mortality after an initial stroke was 6.8% in the first 30 days, 9.4% within 90 days, 17.0% within 1 year, and 45% within 5 years. Patients with hemorrhagic strokes had higher mortality. Treatment in a stroke unit was associated with lower mortality. CONCLUSION Patients with acute stroke should be treated in a specialized center whenever possible. After hospital discharge, stroke patients should be followed up at short intervals and any risk factors for stroke should be treated.
Stress signalling dynamics of the mitochondrial electron transport chain and oxidative phosphorylation system in higher plants.

BACKGROUND Mitochondria play a diversity of physiological and metabolic roles under conditions of abiotic or biotic stress. They may be directly subjected to physico-chemical constraints, and they are also involved in integrative responses to environmental stresses through their central position in cell nutrition, respiration, energy balance and biosyntheses. In plant cells, mitochondria present various biochemical peculiarities, such as cyanide-insensitive alternative respiration, and, besides integration with ubiquitous eukaryotic compartments, their functioning must be coupled with plastid functioning. Moreover, given the sessile lifestyle of plants, their relative lack of protective barriers and present threats of climate change, the plant cell is an attractive model to understand the mechanisms of stress/organelle/cell integration in the context of environmental stress responses. SCOPE The involvement of mitochondria in this integration entails a complex network of signalling, which has not been fully elucidated, because of the great diversity of mitochondrial constituents (metabolites, reactive molecular species, structural and regulatory biomolecules) that are linked to stress signalling pathways. The present review analyses the complexity of stress signalling connexions that are related to the mitochondrial electron transport chain and oxidative phosphorylation system, and how they can be involved in stress perception and transduction, signal amplification, or cell stress response modulation. CONCLUSIONS Plant mitochondria are endowed with a diversity of multi-directional hubs of stress signalling that lead to regulatory loops and regulatory rheostats, whose functioning can amplify and diversify some signals or, conversely, dampen and reduce other signals. Involvement in a wide range of abiotic and biotic responses also implies that mitochondrial stress signalling could result in synergistic or conflicting outcomes during acclimation to multiple and complex stresses, such as those arising from climate change.
Major conformational changes in the structure of lysozyme obtained from a crystal with a very low solvent content.

A new crystal form of lysozyme with a very low solvent content (26.35%) has been obtained in the orthorhombic space group P212121 (with unit-cell parameters a = 30.04, b = 51.68, c = 61.53 Å). The lysozyme structure obtained from these crystals does not show the typical overall fold. Instead, major conformational changes take place in some elements of the secondary structure and in the hydrophobic core of the protein. At the end of the central α-helix (α2), Glu35 is usually buried in the catalytic site and shows an abnormally high pKa value, which is key to the activity of the enzyme. The high pKa value of this glutamate residue is favoured by the hydrophobic environment, particularly by its neighbour Trp108, which is important for structural stability and saccharide binding. In this new structure, Trp108 shows a 90° rotation of its side chain, which results in the rearrangement of the hydrophobic core. Conformational changes also result in the exposure of Glu35 to the solvent, which impairs the catalytic site by increasing the distance between Glu35 and Asp52 and lowering the pKa value of the glutamate. Altogether, this new lysozyme structure reveals major conformational changes in the hydrophobic core and catalytic site that might play a role in the folding and bactericidal function of the protein.
Impact of depression on coping strategies in multiple sclerosis patients.

1Sorin Iova, 2Codruța A. Popescu, 1Andrada Iova, 3Petru Mihancea, 4Anca D. Buzoianu 1 Department of PsychoNeurosciences and Rehabilitation, Oradea University, Faculty of Medicine and Pharmacy, Romania; 2Department of Social Sciences and History of Medicine, University of Medicine and Pharmacy “Iuliu Hațieganu’’, Cluj-Napoca, Romania; 3 Department of Doctoral school in Biosciences, Medicine domain, Oradea University, Faculty of Medicine and Pharmacy, Romania; 4 Department of Pharmacology, Clinical Pharmacology and Toxicology, “Iuliu Hațieganu’’ University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Prevalence of Soil-transmitted Helminths in Primary School Playgrounds in Edo State, Southern Nigeria

Summary Schoolchildren in primary schools are mostly at risk of acquiring soil-transmitted helminths (STHs) infections due to their habits (geophagy, onychophagy and playing with barefoot). Profiling soil parasites on school playgrounds is expected to provide an insight to an array of parasites schoolchildren are constantly at risk of acquiring; and this information could guide on intervention programmes. Soil samples from sixteen primary school playgrounds in Edo State (South-South, Nigeria) were collected over a six-month period both in the dry (January, February and March) and wet (May, June and July) seasons in 2018 and early 2019. Samples were processed and analysed following standard parasitological procedures. Of the 576 soil samples collected, 318(55.2 %) were positive with one or more soil parasites. Generally, the predominant parasites recovered from the total number of soil samples collected were: Ascaris 127(22 %), Strongyloides 111(19.27 %) and hookworm 50(8.68 %). Ascaris was most preponderant in the dry season, while Strongyloides was the most occurring in the wet season. The mean differences in the parasite load for Ascaris and hookworm between dry and wet seasons were not significant; while for Strongyloides it was higher in the wet than dry season. These results could be a consequence of observed poor state of toilet/sanitary facilities as well as the lack or poor state of basic infrastructure like proper drainage and waste disposal systems in the host communities. There is therefore urgent need to interrupt the STHs transmission cycles in the environment and possibly in schoolchildren by instituting sustainable intervention programmes within schools located in STHs endemic regions like southern Nigeria.
Nursing case management for people with hypertension in primary health care: A randomized controlled trial.

INTRODUCTION Hypertension is a chronic disease that requires continuous and long-term care to prevent or delay the development of associated complications. Although various interventions for hypertension exist, case management in Brazil's primary healthcare is understudied. We examined nursing case management effectiveness for controlling blood pressure among Brazilian adults with hypertension in the public healthcare system. METHOD A randomized controlled trial with a 12-month follow-up was conducted at a primary healthcare clinic in southern Brazil. Adult patients with hypertension were randomly allocated to intervention (n = 47) and usual care groups (n = 47). The nursing case management model includes nursing consultations, telephone contact, home visits, health education, and appropriate referrals. Patient outcomes (blood pressure, body mass index, waist circumference, quality of life, treatment adherence) were assessed at baseline and 6- and 12-month follow-up for the intervention group and at baseline and 12-month follow-up for the usual care group. Data were collected from only the intervention group at T6 to avoid contact between the researcher and the usual care group, and to check the care plan and modify it if necessary. RESULTS After the intervention, the intervention group's blood pressure decreased significantly compared to the usual care group. The differences in systolic and diastolic blood pressure between the groups was -8.3 (intervention)/1.1 (usual care) mmHg (p = .004) and -7.4/-0.6 mmHg (p = .007), respectively. The intervention group had significantly greater improvement in waist circumference (-2.0/1.2 cm), body mass index (- 0.4/0.3), and treatment adherence (4.8/-1.1) than the usual care group (all p < .05). CONCLUSION Nursing case management in primary healthcare may be effective for improving outcomes among patients with hypertension.
The roadmap towards elimination of lymphatic filariasis by 2030: insights from quantitative and mathematical modelling

The Global Programme to Eliminate Lymphatic Filariasis was launched in 2000 to eliminate lymphatic filariasis (LF) as a public health problem by 1) interrupting transmission through mass drug administration (MDA) and 2) offering basic care to those suffering from lymphoedema or hydrocele due to the infection. Although impressive progress has been made, the initial target year of 2020 will not be met everywhere. The World Health Organization recently proposed 2030 as the new target year for elimination of lymphatic filariasis (LF) as a public health problem. In this letter, LF modelers of the Neglected Tropical Diseases (NTDs) Modelling Consortium reflect on the proposed targets for 2030 from a quantitative perspective. While elimination as a public health problem seems technically and operationally feasible, it is uncertain whether this will eventually also lead to complete elimination of transmission. The risk of resurgence needs to be mitigated by strong surveillance after stopping interventions and sometimes perhaps additional interventions.
Phosphodiesterase 5 (PDE5) Is Highly Expressed in Cancer-Associated Fibroblasts and Enhances Breast Tumor Progression

The overexpression of phosphodiesterase (PDE) 5 is frequently found in various human cancers, such as those of the breast. However, PDE5’s role in the tumor microenvironment is still unknown. As PDE5 represents a high-value therapeutic target, we investigated whether the expression and function of PDE5 in breast cancer-associated fibroblasts (CAFs) may be clinically relevant to malignant progression. PDE5 expression was increased in human breast cancer stroma compared with normal stroma and was correlated to a shorter overall survival. Treatment of CAFs, isolated from breast tumor biopsies, with selective PDE5 inhibitors inhibited their proliferation, motility, and invasiveness, and negatively controlled tumor–stroma interactions in both ‘in vitro’ and ‘in vivo’ models. PDE5 stable overexpression transformed immortalized mouse embryonic fibroblasts (MEFs) towards an activated fibroblast phenotype, impacting their intrinsic characteristics and paracrine effects on breast cancer cell growth and migration through an enhanced production of the C-X-C motif chemokine 16 (CXCL16). On the other hand, CAF exposure to PDE5 inhibitors was associated with reduced CXCL16 expression and secretion. Importantly, CXCL16 levels in breast cancer stroma showed a strong correlation with PDE5 levels and poor patient outcomes. In conclusion, PDE5 is overexpressed in breast cancer stroma, enhances the tumor-stimulatory activities of fibroblasts, and impacts clinical outcomes; thus, we propose this enzyme as an attractive candidate for prognosis and a potential target for treatments in breast cancer patients.
Transforming Byzantine Faults using a Trusted Execution Environment

We present a general transformation of general omission resilient distributed algorithms into byzantine fault ones. The transformation uses the guarantees of integrity and confidentiality provided by a trusted execution environment to implement a byzantine failure detector. Correct processes in a transformed algorithm will operate as if byzantine faulty processes have crashed or their messages were dropped. The transformation adds no additional messages between processes, except for a pre-compute step, and the increase in states of the algorithm is linearly bounded: it is a 1-round, n=f+1 translation, making no assumptions of determinism.
A Survey on Fog Programming: Concepts, State-of-the-Art, and Research Challenges

With the rapid evolution of the Internet of Things (IoT) and the growth of IoT-generated data, cloud computing platforms have been widely used to store and process this type of data. However, cloud computing cannot handle rapidly emerging smart applications with latency-sensitive, high throughput, and high availability and reliability requirements, such as virtual reality and autonomous vehicles. The fog and mobile edge computing paradigms have been proposed to bring the cloud capacity along the network to end devices to address the above concerns. A key development aspect of fog systems is their programming models. Fog programming models and frameworks face challenges that originated from the unique characteristics of fog systems, such as heterogeneity, scalability, and mobility. In this paper, we first study the main characteristics of fog programming, as well as the design requirements of fog programming models with respect to the fog architecture and application types. Then, we survey fog programming models both from research and industry perspectives. Finally, we point out the issues and future challenges in fog programming. The survey framework, presented in this paper, provides useful insights and outlook for the fog programming research and development, inspires further research on fog programming models, and sheds light on the future of programming in this fast-growing computing paradigm.
DCUDA: Dynamic GPU Scheduling with Live Migration Support

In clouds and data centers, GPU servers which consist of multiple GPUs are widely deployed. Current state-of-the-art GPU scheduling algorithm are "static" in assigning applications to different GPUs. These algorithms usually ignore the dynamics of the GPU utilization and are often inaccurate in estimating resource demand before assigning/running applications, so there is a large opportunity to further load balance and to improve GPU utilization. Based on CUDA (Compute Unified Device Architecture), we develop a runtime system called DCUDA which supports "dynamic" scheduling of running applications between multiple GPUs. In particular, DCUDA provides a realtime and lightweight method to accurately monitor the resource demand of applications and GPU utilization. Furthermore, it provides a universal migration facility to migrate "running applications" between GPUs with negligible overhead. More importantly, DCUDA transparently supports all CUDA applications without changing their source codes. Experiments with our prototype system show that DCUDA can reduce 78.3% of overloaded time of GPUs on average. As a result, for different workloads consisting of a wide range applications we studied, DCUDA can reduce the average execution time of applications by up to 42.1%. Furthermore, DCUDA also reduces 13.3% energy in the light load scenario.
Endurance enhancement of write-optimized STT-RAM caches

Low density and high leakage power of SRAM are the major setbacks for its scalability. Non-volatile memory (NVM) like spin-transfer torque random access memory (STT-RAM) is a suitable replacement for SRAM at the last level cache (LLC). NVM offers high density, and near zero leakage, which are highly desired for on-chip caches. A few drawbacks of STT-RAM such as high write latency and limited endurance, have to be taken care before it can replace SRAM at the LLC. Prior works have either tried to optimize the write latency or endurance. In this paper, by considering write-optimized STT-RAM, we propose endurance improvement techniques by reducing the maximum number of writes, global write variation, and the average number of writes. We take care of low retention time of write-optimized STT-RAMs using a refresh mechanism. We employ refresh-aware cache replacement policies wherein the cache blocks that are about to expire are preferred to the recently refreshed cache blocks. This refresh-aware policy, when combined with the recency information of the cache blocks, enhances both performance and endurance of STT-RAM LLC. We show that our refresh-aware policy achieves the maximum lifetime improvement of 32.5% for single-core and 70.7% for muti-core compared to STT-RAM with no wear leveling. When we combine recency information with our refresh-aware policy, there is a slight improvement in the performance.