Miracle-dz/UniFAR-FTUs huggingface dataset:
RPAcan3990: an Ultrasensitive Recombinase Polymerase Assay To Detect Angiostrongylus cantonensis DNA

Angiostrongylus cantonensis is one of the leading causes of eosinophilic meningitis worldwide. A field-deployable molecular detection method could enhance both environmental surveillance and clinical diagnosis of this emerging pathogen. ABSTRACT Angiostrongylus cantonensis is one of the leading causes of eosinophilic meningitis worldwide. A field-deployable molecular detection method could enhance both environmental surveillance and clinical diagnosis of this emerging pathogen. Accordingly, RPAcan3990, a recombinase polymerase assay (RPA), was developed to target a region predicted to be highly repeated in the A. cantonensis genome. The assay was then adapted to produce a visually interpretable fluorescent readout using an orange camera lens filter and a blue light. Using A. cantonensis genomic DNA, the limit of detection was found to be 1 fg/μl by both fluorometer measurement and visual reading. All clinical samples known to be positive for A. cantonensis from various areas of the globe were positive by RPAcan3990. Cerebrospinal fluid samples from other etiologies of eosinophilic meningitis (i.e., Toxocara sp. and Gnathostoma sp.) were negative in the RPAcan3990 assay. The optimal incubation temperature range for the reaction was between 35°C and 40°C. The assay successfully detected 1 fg/μl of A. cantonensis genomic DNA after incubation at human body temperature (in a shirt pocket). In conclusion, these data suggest RPAcan3990 is potentially a point-of-contact molecular assay capable of sensitively detecting A. cantonensis by producing visually interpretable results with minimal instrumentation.
Structural and Optical Property of Core-shell Tio 2 /Sno 2 Nanocomposites Exhibiting Photocatalytic Behavior

Here we report on the morphological and optical properties of TiO 2 /SnO 2 nanocomposites prepared by a sol-gel method. The method comprises of a simple chemical reaction between Titanium isopropoxide solution and Water as well as subsequent addition of SnCl 2 solution to avail the coating of SnO 2 layer on the surface of TiO 2 nanoparticles. The as synthesized TiO 2 nanoparticles display strong UV absorbance characteristics. The XRD patterns verify the anatase phase of TiO 2 nanoparticles. The presence of both TiO 2 and SnO 2 in the sample is confirmed through XRD pattern. HRTEM images show clear evidence of formation of composite(coreshell) nanostructure in the sample. Optical properties of both TiO 2 and composite TiO 2 /SnO 2 nanostructures are studied using UV-Vis absorption spectra, Photoluminescence and FTIR spectra. The performance of the composite nanostructure as a photocatalytic agent in comparison to the core TiO 2 nanostructures is also investigated for methyl orange dye under illumination of light. The Urbach energy of both the system is calculated and correlated with the photocatalytic degradation.
NON-ISOTHERMAL MULTIPHASE FLOW AND MULTICOMPONENT REACTIVE TRANSPORT MODELS IN POROUS MEDIA

The FEBEX project (Full Scale Engineered Barriers Experiment), was promoted by ENRESA and financed by the European Commission to study the behavior of the near field of a high-level radioactive waste repository (HLW) in crystalline rock. The FEBEX experiment has the multiple objective of demonstrating the feasibility of constructing and assembling the engineered barriers and of developing methodologies and models to evaluate the thermo-hydro-mechanical (THM) and thermo-hydro-geochemical (THG) behavior of the near field. To fulfill the needs of the FEBEX project, a THG numerical code was developed, FADES-CORE). FADES-CORE (14) allows thermo-hydro-geochemical simulation of unsaturated porous media with multiphase flow. The code has the following characteristics: The soil is comprised of a solid core (mineral phases), a liquid phase (mobile water, dissolved air and solutes) and a gas phase (vapor and dry air). The code solves the equations of water and air flow and solute transport, heat transport and chemical reactions. Chemical reactions include: aqueous complexation, acid-base, redox, cation exchange, adsorption, dissolution- precipitation and gas dissolution/exolution. Radioactive decay reactions and anion exclusion are also considered. Here we present the physical and mathematical formulation of the problem as well as the main numerical characteristics of FADES-CORE. The code has been developed by adding solute transport and geochemical subroutines to the existing code FADES (10). FADES is a code that solves the thermo-hydro-mechanical (THM) behavior of porous media. Therefore, FADES-CORE also allows for the simulatation of the mechanical process. After a thorough verification, the predictive ability of FADES-CORE has been checked against laboratory tests designed to study and understand the processes that take place in the clay barrier under controlled conditions. In these tests it is necessary to quantify evaporation-condensation processes taking place near the heaters. The thermal-hydraulic cells, a "mock-up" test and an "in situ" test (under natural conditions) have been modeled and provided excellent results (13) and (15).
Expression of the fructose transporter GLUT5 in patients with fructose malabsorption

Abstract Background Patients with abdominal symptoms are frequently diagnosed with fructose malabsorption (FM). Fructose is absorbed by monosaccharide transporters located in the brush border of the human small intestine. The aim of this study was to investigate the histoanatomical distribution of the main fructose transporter GLUT5. Materials and methods We studied 223 patients diagnosed with FM by a hydrogen breath test and grouped according to their response to a fructose-free diet. The control group were 42 healthy individuals and 29 patients with celiac disease (CD). The fructose breath test was done with 50 g fructose. The expression of Glut5 in duodenal biopsy specimens was studied by immunohistochemistry. The Kruskal-Wallis-test and Mann-Whitney U-test were used to carry out the statistical analysis. Results The histoanatomical expression pattern of GLUT5 did not differ significantly between those patients with FM who responded completely to a fructose-free diet (n = 183) and healthy individuals (n = 42); nor did it correlate to H2 production measured in fructose breath testing. In patients with FM, the GLUT5 expression pattern did not differ between those individuals responding to a fructose-free diet and those who did not. However, GLUT5 expression pattern was significantly different in patients with CD (n = 29) compared to patients with FM and to healthy individuals (p = 0.009). Conclusion GLUT5 expression patterns are not be related to adult patients with FM. However, in secondary malabsorption, a decreased GLUT5 expression was found. Further investigation is needed to understand the essential factors in FM and the influence on functional gastrointestinal disorders.
Awareness, Utilization, and Preferences for Traditional and Contemporary HIV Prevention Strategies Among Facebook and Instagram-Using MSM in the United States

HIV prevention research among men who have sex with men (MSM) has traditionally focused on individual risk reduction strategies. Our study evaluated awareness, utilization, and preferences for 10 complementary HIV prevention strategies among 1,286 MSM recruited via Facebook and Instagram from June-August 2018. Ages ranged from 18-85 years, and the majority were non-Hispanic white (n = 1,019, 79.24%), college-educated (n = 819, 63.69%), gay-identifying (n = 1,074, 83.51%), and partnered (n = 808, 62.83%). Post-exposure prophylaxis was the least familiar option, and engaging in sexual activities other than anal sex was the most utilized option. Progressively older and bisexual-identifying MSM were less likely, but those with higher educational levels and easy access to local HIV resources were more likely to be aware of and to be utilizing a greater number of strategies. Additionally, Hispanic MSM were less likely to be aware of, and those in a “closed” relationship were less likely to be utilizing a greater number of strategies. In a subset of 775 multiple strategy users, pre-exposure prophylaxis, regularly testing for HIV, and limiting the number of sex partners emerged as the most preferred options. Combination intervention packages for MSM should be tailored to personal circumstances, including sexual orientation, relationship characteristics and access to local HIV resources.
The Serum Proteome and Ursodeoxycholic Acid Response in Primary Biliary Cholangitis

Stratified therapy has entered clinical practice in primary biliary cholangitis (PBC), with routine use of second‐line therapy in nonresponders to first‐line therapy with ursodeoxycholic acid (UDCA). The mechanism for nonresponse to UDCA remains, however, unclear and we lack mechanistic serum markers. The UK‐PBC study was established to explore the biological basis of UDCA nonresponse in PBC and identify markers to enhance treatment.
Involvement of End Users in the Development of Serious Games for Health Care Professions Education: Systematic Descriptive Review

Background On the basis of ethical and methodological arguments, numerous calls have been made to increase the involvement of end users in the development of serious games (SGs). Involving end users in the development process is considered a way to give them power and control over educational software that is designed for them. It can also help identify areas for improvement in the design of SGs and improve their efficacy in targeted learning outcomes. However, no recognized guidelines or frameworks exist to guide end users’ involvement in SG development. Objective The aim of this study is to describe how end users are involved in the development of SGs for health care professions education. Methods We examined the literature presenting the development of 45 SGs that had reached the stage of efficacy evaluation in randomized trials. One author performed data extraction using an ad hoc form based on a design and development framework for SGs. Data were then coded and synthesized on the basis of similarities. The coding scheme was refined iteratively with the involvement of a second author. Results are presented using frequencies and percentages. Results End users’ involvement was mentioned in the development of 21 of 45 SGs. The number of end users involved ranged from 12 to 36. End users were often involved in answering specific concerns that arose during the SG design (n=6) or in testing a prototype (n=12). In many cases, researchers solicited input from end users regarding the goals to reach (n=10) or the functional esthetics of the SGs (n=7). Most researchers used self-reported questionnaires (n=7). Conclusions Researchers mentioned end users’ involvement in the development of less than half of the identified SGs, and this involvement was also poorly described. These findings represent significant limitations to evaluating the impact of the involvement of end users on the efficacy of SGs and in making recommendations regarding their involvement.
Age-Related Macular Degeneration: Pathophysiology, Management, and Future Perspectives

Among older adults, age-related macular degeneration (AMD) is a prevalent disabling condition that begins as subtle visual disturbances and can progress to permanent loss of central vision. In its late neovascular form, AMD is treatable with inhibitors of vascular endothelial growth factor, the key driver of exudative disease. In the atrophic form, treatment remains elusive. This review addresses the natural history of AMD – through early, intermediate, and advanced disease stages – and concentrates on diagnosis and risk stratification, deficiencies of current treatments, and the promising findings of emerging therapies.
HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

HER2-positive breast cancers are among the most heterogeneous breast cancer subtypes. The early amplification of HER2 and its known oncogenic isoforms provide a plausible mechanism in which distinct programs of tumor heterogeneity could be traced to the initial oncogenic event. Here a Cancer rainbow mouse simultaneously expressing fluorescently barcoded wildtype (WTHER2), exon-16 null (d16HER2), and N-terminally truncated (p95HER2) HER2 isoforms is used to trace tumorigenesis from initiation to invasion. Tumorigenesis was visualized using whole-gland fluorescent lineage tracing and single-cell molecular pathology. We demonstrate that within weeks of expression, morphologic aberrations were already present and unique to each HER2 isoform. Although WTHER2 cells were abundant throughout the mammary ducts, detectable lesions were exceptionally rare. In contrast, d16HER2 and p95HER2 induced rapid tumor development. d16HER2 incited homogenous and proliferative luminal-like lesions which infrequently progressed to invasive phenotypes whereas p95HER2 lesions were heterogenous and invasive at the smallest detectable stage. Distinct cancer trajectories were observed for d16HER2 and p95HER2 tumors as evidenced by oncogene-dependent changes in epithelial specification and the tumor microenvironment. These data provide direct experimental evidence that intratumor heterogeneity programs begin very early and well in advance of screen or clinically detectable breast cancer. Implications: Although all HER2 breast cancers are treated equally, we show a mechanism by which clinically undetected HER2 isoforms program heterogenous cancer phenotypes through biased epithelial specification and adaptations within the tumor microenvironment. Visual Overview
Intrinsic OXPHOS limitations underlie cellular bioenergetics in leukemia

Currently there is great interest in targeting mitochondrial oxidative phosphorylation (OXPHOS) in cancer. However, notwithstanding the targeting of mutant dehydrogenases, nearly all hopeful ‘mito-therapeutics’ cannot discriminate cancerous from non-cancerous OXPHOS and thus suffer from a limited therapeutic index. Using acute myeloid leukemia (AML) as a model, herein, we leveraged an in-house diagnostic biochemical workflow to identify ‘actionable’ bioenergetic vulnerabilities intrinsic to cancerous mitochondria. Consistent with prior reports, AML growth and proliferation was associated with a hyper-metabolic phenotype which included increases in basal and maximal respiration. However, despite having nearly 2-fold more mitochondria per cell, clonally expanding hematopoietic stem cells, leukemic blasts, as well as chemoresistant AML were all consistently hallmarked by intrinsic OXPHOS limitations. Remarkably, by performing experiments across a physiological span of ATP free energy, we provide direct evidence that leukemic mitochondria are particularly poised to consume ATP. Relevant to AML biology, acute restoration of oxidative ATP synthesis proved highly cytotoxic to leukemic blasts, suggesting that active OXPHOS repression supports aggressive disease dissemination in AML. Together, these findings argue against ATP being the primary output of leukemic mitochondria and provide proof-of-principle that restoring, rather than disrupting, OXPHOS may represent an untapped therapeutic avenue for combatting hematological malignancy and chemoresistance.
Submolecular imaging with single particleatomic force sensors

Scanning probe methods with decorated tips is a new trend in surface study. An application of complex probe like a tip with an attached single molecule or single atom allows to get new details about the surface properties. It has been shown that the scanning tunnelling hydrogen microscopy (STHM) approach can reach atomic scale resolution and reveals intermolecular interactions. Because of the complexity, this new rapidly developing area is not yet fully understood. In this work systematic studies of tips decorated with Xe, H2, D2, CO, CH4 was carried out. The tip with a single atom or a single molecule creates a single particle sensor that simultaneously performs the function of an atomicscale force sensor and a signal transducer, which couples the short-range force acting on the tip to the tunnelling conductance of the junction. In some cases the sensor-transducer function of the decorated STM tips can be quantitatively calibrated. Differences in the performance of the studied sensors suggest that the sensor functionality can be modified by tuning the interaction between the sensor particle and the STM tip. Based on forcefield calculations, theoretical analysis of the single particle sensor shows an interrelation between the relative movement of the particle on the tip and contrast structure of the surface images.
Written benefit finding for improving psychological health during the Covid-19 pandemic first wave lockdown

Abstract Objectives. Written benefit finding is known to improve psychological and physical health in a range of patient groups. Here, we tested the efficacy of written benefit finding, delivered online during the Covid-19 pandemic lockdown, on mood and physical symptoms. We also investigated perseverative thinking as a moderator of these effects. Design. A quantitative longitudinal design was employed. Main Outcome Measures. Participants (n = 91) completed self-report measures of anxiety, depression, stress and physical symptoms at baseline, and two weeks after being randomised to complete three consecutive days of writing about the positive thoughts and feelings they experienced during the pandemic (written benefit finding) or to unemotively describe the events of the previous day (control). State anxiety was measured immediately before and after writing. Perseverative thinking was measured at baseline. Results. Anxiety and depression symptoms decreased between baseline and the two week follow-up, but did not differ significantly between the two conditions. Perseverative thinking was negatively associated with changes in symptoms of anxiety, depression and stress, but did not moderate any writing effects. There was a significant reduction in state anxiety in the written benefit finding condition. Conclusions. Written benefit finding may be a useful intervention for short-term improvements in wellbeing.
Expanding the genetic landscape of oral‐facial‐digital syndrome with two novel genes

Oral‐facial‐digital syndromes (OFDS) are a heterogeneous and rare group of Mendelian disorders characterized by developmental abnormalities of the oral cavity, face, and digits caused by dysfunction of the primary cilium, a mechanosensory organelle that exists atop most cell types that facilitates organ patterning and growth. OFDS is inherited both in an X‐linked dominant, X‐linked recessive, and autosomal recessive manner. Importantly, though many of the causal genes for OFDS have been identified, up to 40% of OFD syndromes are of unknown genetic basis. Here we describe three children with classical presentations of OFDS including lingual hamartomas, polydactyly, and characteristic facial features found by exome sequencing to harbor variants in causal genes not previously associated with OFDS. We describe a female with hypothalamic hamartoma, urogenital sinus, polysyndactyly, and multiple lingual hamartomas consistent with OFDVI with biallelic pathogenic variants in CEP164, a gene associated with ciliopathy‐spectrum disease, but never before with OFDS. We additionally describe two unrelated probands with postaxial polydactyly, multiple lingual hamartomas, and dysmorphic features both found to be homozygous for an identical TOPORS missense variant, c.29 C>A; (p.Pro10Gln). Heterozygous TOPORS pathogenic gene variants are associated with autosomal dominant retinitis pigmentosa, but never before with syndromic ciliopathy. Of note, both probands are of Dominican ancestry, suggesting a possible founder allele.
Can a social media intervention improve online communication about suicide? A feasibility study examining the acceptability and potential impact of the #chatsafe campaign

There is a need for effective and youth-friendly approaches to suicide prevention, and social media presents a unique opportunity to reach young people. Although there is some evidence to support the delivery of population-wide suicide prevention campaigns, little is known about their capacity to change behaviour, particularly among young people and in the context of social media. Even less is known about the safety and feasibility of using social media for the purpose of suicide prevention. Based on the #chatsafe guidelines, this study examines the acceptability, safety and feasibility of a co-designed social media campaign. It also examines its impact on young people’s willingness to intervene against suicide and their perceived self-efficacy, confidence and safety when communicating on social media platforms about suicide. A sample of 189 young people aged 16–25 years completed three questionnaires across a 20-week period (4 weeks pre-intervention, immediately post-intervention, and at 4-week follow up). The intervention took the form of a 12-week social media campaign delivered to participants via direct message. Participants reported finding the intervention acceptable and they also reported improvements in their willingness to intervene against suicide, and their perceived self-efficacy, confidence and safety when communicating on social media about suicide. Findings from this study present a promising picture for the acceptability and potential impact of a universal suicide prevention campaign delivered through social media, and suggest that it can be safe to utilize social media for the purpose of suicide prevention.
Cache-aware Sparse Patterns for the Factorized Sparse Approximate Inverse Preconditioner

Conjugate Gradient is a widely used iterative method to solve linear systems Ax=b with matrix A being symmetric and positive definite. Part of its effectiveness relies on finding a suitable preconditioner that accelerates its convergence. Factorized Sparse Approximate Inverse (FSAI) preconditioners are a prominent and easily parallelizable option. An essential element of a FSAI preconditioner is the definition of its sparse pattern, which constraints the approximation of the inverse A-1. This definition is generally based on numerical criteria. In this paper we introduce complementary architecture-aware criteria to increase the numerical effectiveness of the preconditioner without incurring in significant performance costs. In particular, we define cache-aware pattern extensions that do not trigger additional cache misses when accessing vector x in the y=Ax Sparse Matrix-Vector (SpMV) kernel. As a result, we obtain very significant reductions in terms of average solution time ranging between 12.94% and 22.85% on three different architectures - Intel Skylake, POWER9 and A64FX - over a set of 72 test matrices.