Miracle-dz/UniFAR-FTUs huggingface dataset:
De Novo p.Asp3368Gly Variant of Dystrophin Gene Associated with X-Linked Dilated Cardiomyopathy and Skeletal Myopathy: Clinical Features and In Silico Analysis

Dystrophin (DMD) gene mutations are associated with skeletal muscle diseases such as Duchenne and Becker Muscular Dystrophy (BMD) and X-linked dilated cardiomyopathy (XL-DCM). To investigate the molecular basis of DCM in a 37-year-old woman. Clinical and genetic investigations were performed. Genetic testing was performed with whole exome sequencing (WES) using the Illumina platform. According to the standard protocol, a variant found by WES was confirmed in all available members of the family by bi-directional capillary Sanger resequencing. The effect of the variant was investigated by using an in silico prediction of pathogenicity. The index case was a 37-year-old woman diagnosed with DCM at the age of 33. A germline heterozygous A>G transversion at nucleotide 10103 in the DMD gene, leading to an aspartic acid–glycine substitution at the amino acid 3368 of the DMD protein (c.10103A>G p.Asp3368Gly), was identified and confirmed by PCR-based Sanger sequencing of the exon 70. In silico prediction suggests that this variant could have a deleterious impact on protein structure and functionality (CADD = 30). The genetic analysis was extended to the first-degree relatives of the proband (mother, father, and sister) and because of the absence of the variant in both parents, the p.Asp3368Gly substitution was considered as occurring de novo. Then, the direct sequencing analysis of her 8-year-old son identified as hemizygous for the same variant. The young patient did not present any signs or symptoms attributable to DCM, but reported asthenia and presented with bilateral calf hypertrophy at clinical examination. Laboratory testing revealed increased levels of creatinine kinase (maximum value of 19,000 IU/L). We report an early presentation of dilated cardiomyopathy in a 33-year-old woman due to a de novo pathogenic variant of the dystrophin (DMD) gene (p.Asp3368Gly). Genetic identification of this variant allowed an early diagnosis of a skeletal muscle disease in her son.
Hedgehog on the Move: Glypican-Regulated Transport and Gradient Formation in Drosophila

Glypicans (Glps) are a family of heparan sulphate proteoglycans that are attached to the outer plasma membrane leaflet of the producing cell by a glycosylphosphatidylinositol anchor. Glps are involved in the regulation of many signalling pathways, including those that regulate the activities of Wnts, Hedgehog (Hh), Fibroblast Growth Factors (FGFs), and Bone Morphogenetic Proteins (BMPs), among others. In the Hh-signalling pathway, Glps have been shown to be essential for ligand transport and the formation of Hh gradients over long distances, for the maintenance of Hh levels in the extracellular matrix, and for unimpaired ligand reception in distant recipient cells. Recently, two mechanistic models have been proposed to explain how Hh can form the signalling gradient and how Glps may contribute to it. In this review, we describe the structure, biochemistry, and metabolism of Glps and their interactions with different components of the Hh-signalling pathway that are important for the release, transport, and reception of Hh.
A multicentre, double-blind, placebo-controlled randomized trial of Mycobacterium w in critically ill patients with COVID-19 (ARMY-2)

ABSTRACT Background: Mycobacterium w (Mw), an immunomodulator, resulted in better clinical status in severe coronavirus infectious disease 19 (COVID-19) but no survival benefit in a previous study. Herein, we investigate whether Mw could improve clinical outcomes and survival in COVID-19. Materials and Methods: In a multicentric, randomized, double-blind, parallel-group, placebo-controlled trial, we randomized hospitalized subjects with severe COVID-19 to receive either 0.3 mL/day of Mw intradermally or a matching placebo for three consecutive days. The primary outcome was 28-day mortality. The co-primary outcome was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The key secondary outcomes were the change in sequential organ failure assessment (SOFA) score on days 7 and 14 compared to the baseline, treatment-emergent adverse events, and others. Results: We included 273 subjects (136 Mw, 137 placebo). The use of Mw did not improve 28-day survival (Mw vs. placebo, 18 [13.2%] vs. 12 [8.8%], P = 0.259) or the clinical status on days 14 (odds ratio [OR], 1.33; 95% confidence intervals [CI], 0.79-2.3), 21 (OR, 1.49; 95% CI, 0.83-2.7) or 28 (OR, 1.49; 95% CI, 0.79-2.8) between the two study arms. There was no difference in the delta SOFA score or other secondary outcomes between the two groups. We observed higher injection site reactions with Mw. Conclusion: Mw did not reduce 28-day mortality or improve clinical status on days 14, 21 and 28 compared to placebo in patients with severe COVID-19. [Trial identifier: CTRI/2020/04/024846]
Updated Clinical Classification and Hemodynamic Definitions of Pulmonary Hypertension and Its Clinical Implications

Pulmonary hypertension (PH) refers to a pathologic elevation of the mean pulmonary artery pressure (mPAP) and is associated with increased morbidity and mortality in a wide range of medical conditions. These conditions are classified according to similarities in pathophysiology and management in addition to their invasive hemodynamic profiles. The 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension present the newest clinical classification system and includes significant updates to the hemodynamic definitions. Pulmonary hypertension is now hemodynamically defined as an mPAP > 20 mmHg, reduced from the previous threshold of ≥25 mmHg, due to important insights from both normative and prognostic data. Pulmonary vascular resistance has been extended into the definition of pre-capillary pulmonary hypertension, with an updated threshold of >2 Wood Units (WU), to help differentiate pulmonary vascular disease from other causes of increased mPAP. Exercise pulmonary hypertension has been reintroduced into the hemodynamic definitions and is defined by an mPAP/cardiac output slope of >3 mmHg/L/min between rest and exercise. While these new hemodynamic thresholds will have a significant impact on the diagnosis of pulmonary hypertension, no evidence-based treatments are available for patients with mPAP between 21–24 mmHg and/or PVR between 2–3 WU or with exercise PH. This review highlights the evidence underlying these major changes and their implications on the diagnosis and management of patients with pulmonary hypertension.
Ecological factors influencing fish distribution in a large subarctic lake system

The coastal climate and frequent wind storms in southwest Alaska create an atypical thermal environment (non-stratified in summer) in the remote Ugashik lakes. This study documents the distribution of lake trout Salvelinus namaycush, Arctic char S. alpinus, Dolly Varden S. malma, Arctic grayling Thymallus arcticus, round whitefish Prosopium cylindraceum, and pygmy whitefish P. coulterii relative to depth, substrate particle size, food habits, length, and age in the absence of strong thermal structure. Sample sites were randomly chosen within sampling strata and gill nets were set at each site. Lake trout and round whitefish were most abundant and had the oldest individuals in the catch. In more typical thermally stratified lake systems lake trout and Arctic char usually move to colder, deeper water in summer. In the Ugashik lakes, however, both species were abundant in shallow water all summer. Prior to this study pygmy whitefish were undocumented in this system. The fish examined in the Ugashik lakes were opportunistic feeders, consuming organisms such as isopods and amphipods. Fish in the Ugashik lakes were found in locations different from what one would expect from predominant literature. Fisheries managers may need to take this into account in their fisheries management. Signature page. i Title page. ji Abstract. in Table of contents. iv List of Figures.vi List of Figures.vi List of Tables. vii Acknowledgements.x Introduction.1 Study Area. 4 Methods.5 Biological Sampling. 5 Gear.5 Experimental design. 5 Shoreline Sites.8 Offshore Sites . 8 Data Collection. 8 Data Analyses.9 Time.9 Depth.11 Length and Age . 11 Substrate.11 Food habits.12 Results.14 Time.14 Depth.14 Length.14 Age.19 Substrate. 22 Food habits. 26 Lake trout diet.28 Arctic char diet.28 Dolly Varden d ie t. 37 Arctic grayling d ie t. 37 Round whitefish diet. 46 iv Table of contents Page Pygmy whitefish diet Discussion. Time. Depth . Length and age. Substrate. Food habits. Conclusion. Recommendations. Literature cited. v 46 53 53 rr a OH56 ,57 . 59 . 64 . 66
Advancing brain-inspired computing with Hybrid Neural networks

Brain-inspired computing, drawing inspiration from the fundamental structure and information-processing mechanisms of the human brain, has gained significant momentum in recent years. It has emerged as a research paradigm centered around brain-computer dual-driven and multi-network integration. One noteworthy instance of this paradigm is the Hybrid Neural Network (HNN), which integrates computer-science-oriented artificial neural networks with neuroscience-oriented spiking neural networks. HNNs exhibit distinct advantages in various intelligent tasks, including perception, cognition, and learning. This paper presents a comprehensive review of HNNs with an emphasis on their origin, concepts, biological perspective, construction framework, and supporting systems. Furthermore, insights and suggestions for potential research directions are provided aiming to propel the advancement of the HNN paradigm.
CEGAH KANKER DENGAN POLA HIDUP CERDIK DAN PATUH DI RT 001/ RW 008 KELURAHAN PONDOK LABU

Indonesia memiliki prevalensi penyakit kanker pada semua usia. Salah satu program pemerintah dalam pengendalian penyakit tidak menular yaitu program CERDIK merupakan pesan singkatan, yaitu C: cek kondisi kesehatan secara berkala, E: enyahkan asap rokok, R: rajin aktifitas fisik, D: diit sehat dengan kalori seimbang, I: istirahat yang cukup, K: kendalikan stress. Dan Pprogram PATUH yaitu P: Periksa kesehatan secara rutin dan ikuti anjuran dokter, A: atasi penyakit dengan pengobatan yang tepat dan teratur, T: tetap diit sehat dengan gizi seimbang, U: upayakan beraktifitas fisik dengan aman, H: hindari rokok, alkohol dan zat karsinogenik lainnya. Kegiatan pengabdian masyarakat ini bertujuan untuk memberikan edukasi pencegahan kanker, sehingga Masyarakat lebih perduli dengan penyakit ini. Metode pelaksanaannya menggunakan pemeriksaan fisik, dan edukasi. Sebelum dan setelah pemberian edukasi, Masyarakat diberikan kuesioner untuk mengidentifikasi pengetahuan Masyarakat sebelum dan setelah diberikan edukasi tentang pencegahan kanker. Hasil kegiatan pengabdian kepada Masyarakat didapatkan bahwa Faktor risiko kanker pada peserta adalah kurang berolahraga dan memiliki berat badan berlebih. Masyarakat menyimak pemberian edukasi dan antusia bertanya, dan pengetahuan peserta meningkat dari 52,9% menjadi 88,2%. Disarankan program CERDIK dan PATUH ini senantiasa disosialisakan untuk meningkatkan rasa peduli masyarakat sehingga mereka dapat mencegah terjadinya kanker.
LOW NOISE MEASUREMENT OF PHOTOCURRENT FOR CONTINUOUS GLUCOSE MONITORING - Low Noise Measurement System Enables Continuous Monitoring of Glucose in Subcutaneous Interstitial Fluid

The purpose of this work is mainly to manufacture several anatomical models in a polymeric material – polydimensiloxane (PDMS) to study the blood flow through a carotid artery bifurcation. Over the last few decades, research has been shown that the geometry of the carotid artery is closely related to the development of serious cardiovascular diseases. Hence, there is a considerable interest in the development of in vitro experimental techniques able to obtain accurate measurements of the blood flow behavior through a realistic carotid artery. In this study we decide to apply rapid prototyping (RP) technologies combined with a PDMS casting technique in order to fabricate an anatomically realistic model of a human carotid to investigate, in a near future, the effect of the geometry on the local hemodynamics and consequently improve the understanding of the origin and development of these pathologies. Based on a human carotid computerized tomography (TC) it has been developed a 3D model through the application of two rapid prototyping techniques – Fused Deposition Modeling (FDM) and Tridimensional Printing (TDP). By combining the rapid prototyping techniques with a PDMS casting technique it was possible at the end to obtain an anatomically transparent model of a human carotid artery made by an elastomeric material, i.e. PDMS. Hence, we believe that this combination is a promising technique to perform in vitro blood studies through anatomically realistic models, such as a carotid artery.
Deciphering the impact of endoparasitic infection on immune response and gut microbial composition of Channa punctata

Intestinal parasitic infections caused by helminths are globally distributed and are a major cause of morbidity worldwide. Parasites may modulate the virulence, gut microbiota diversity and host responses during infection. Despite numerous works, little is known about the complex interaction between parasites and the gut microbiota. In the present study, the complex interplay between parasites and the gut microbiota was investigated. A total of 12 bacterial strains across four major families, including Enterobacteriaceae, Morganellaceae, Flavobacteriaceae, and Pseudomonadaceae, were isolated from Channa punctata, infected with the nematode species Aporcella sp. , Axonchium sp. , Tylencholaimus mirabilis, and Dioctophyme renale. The findings revealed that nematode infection shaped the fish gut bacterial microbiota and significantly affected their virulence levels. Nematode-infected fish bacterial isolates are more likely to be pathogenic, with elevated hemolytic activity and biofilm formation, causing high fish mortality. In contrast, isolates recovered further from non-parasitised C. punctata were observed to be non-pathogenic and had negligible hemolytic activity and biofilm formation. Antibiogram analysis of the bacterial isolates revealed a disproportionately high percentage of bacteria that were either marginally or multidrug resistant, suggesting that parasitic infection-induced stress modulates the gut microenvironment and enables colonization by antibiotic-resistant strains. This isolation-based study provides an avenue to unravel the influence of parasitic infection on gut bacterial characteristics, which is valuable for understanding the infection mechanism and designing further studies aimed at optimizing treatment strategies. In addition, the cultured isolates can supplement future gut microbiome studies by providing wet lab specimens to compare (meta)genomic information discovered within the gut microenvironment of fish.
Can acupuncture increase microcirculation in peripheral artery disease and diabetic foot syndrome? – a pilot study

Background Globally, diabetes mellitus (DM) and peripheral artery disease (PAD) have an increasing incidence and a high prevalence and are both associated with high morbidity and complication rates, e.g., as chronic non-healing peripheral ulcers. Impaired macro- and microcirculation and peripheral neuropathy lead to an increased risk of foot ulcers and infections. These complications are difficult to treat, have a high risk of becoming chronic and often lead to lower limb amputation. The aim of this planned study was to investigate the potential effects of acupuncture on improving microcirculation in patients with Diabetic Foot Syndrome (DFS) and PAD. Materials and methods In 18 patients with chronic non-healing peripheral ulcers and diagnosed DM or PAD, data on 8 microcirculatory parameters were collected simultaneously on intact skin close to the wound margin. Microcirculation was assessed using an O2C device combining laser Doppler shift and white light spectroscopy (LEA Medizintechnik GmbH, Giessen, Germany). Unilateral and bilateral acupuncture was performed on the connecting line between acupuncture points Stomach 14 and Stomach 15. Results After unilateral acupuncture (ipsilateral to the wound side), a statistically significant improvement in 7 out of 8 microcirculatory parameters was demonstrated compared to baseline measurements before acupuncture. After bilateral acupuncture, there was an additional improvement and statistical significance in all parameters in both DFS and PAD patients. Discussion These results show an improvement in the microcirculation and peripheral blood flow at the edges of the wound. As impaired micro- and macrocirculation is considered to be a critical prognostic factor for the healing of a peripheral lesion, the intervention could have a positive impact on the healing of (chronic) peripheral wounds.
Plasma-Facing Components in Tokamaks : Material Modification and Fuel Retention

A set of stainless steel (SS) and molybdenum mirror samples located in the divertor and at the outer mid-plane of the vessel were exposed in JET from 2005 to 2007. A selection of these mirror samples with well adhered deposits (i.e. not flaking) of up to a few hundred nanometers in thickness and with Be/C ratios ranging from 0 to similar to 1 have been cleaned using a laser system developed at CEA, Saclay. Following laser cleaning the recovered reflectivity was generally better in the infrared than the visible spectrum, with recovery of up to 90% of the initial reflectivity being obtained at 1600 nm for both Mo and SS mirrors falling as low as 20-30% of initial reflectivity at a wavelength of 400 nm for some SS mirrors, rising to similar to 80% for Mo mirrors. Some deposit remained on the mirrors after the cleaning trials.
Nicotine, Humectants, and Tobacco-Specific Nitrosamines (TSNAs) in IQOS Heated Tobacco Products (HTPs): A Cross-Country Study

Heated Tobacco Products (HTPs) purport to reduce exposure to tobacco-related toxicants compared to combustible cigarettes. This cross-sectional study examined the content of nicotine, two humectants (propylene glycol (PG) and vegetable glycerin (VG)), and four tobacco-specific nitrosamines (TSNAs: NNN, NNK, NAT, and NAB) in the tobacco filler of a popular HTP brand (IQOS). Non-menthol and menthol IQOS sticks were purchased from nine countries between 2017 and 2020 and were classified into two versions (“Bold” and “Light”) using Philip Morris’s flavor descriptors. The average nicotine concentration was 4.7 ± 0.5 mg/stick, and the highest nicotine concentration was found in products from Japan (5.1 ± 0.2 mg/stick). VG was the dominant humectant found in all sticks, with an average concentration of (31.5 ± 2.3 mg/stick). NNN, NNK, and NAT were substantially higher in the “Bold” sticks than the “Light” sticks. Significant differences between countries for TSNAs were also observed: the NAT and NAB contents were the highest in the “Light” products from Canada (192.5 ± 24.1 and 22.9 ± 1.0 ng/stick, respectively); the NNK concentration was the highest in the “Bold” products from Poland (64.8 ± 7.9 ng/stick); and the highest NNN concentrations were observed in the “Bold” products from South Africa (488.9 ± 26.7 ng/stick). As NNN and NNK are known human carcinogens, and as humectants like PG and VG can degrade into toxic carbonyl compounds upon heating, monitoring the concentration of these chemicals in HTPs is important for protecting users’ health and ensuring compliance with regulations.
Pathophysiological Roles of Ion Channels in Epidermal Cells, Immune Cells, and Sensory Neurons in Psoriasis

Psoriasis is a chronic inflammatory skin disease characterized by the rapid abnormal growth of skin cells in the epidermis, driven by an overactive immune system. Consequently, a complex interplay among epidermal cells, immune cells, and sensory neurons contributes to the development and progression of psoriasis. In these cellular contexts, various ion channels, such as acetylcholine receptors, TRP channels, Ca2+ release-activated channels, chloride channels, and potassium channels, each serve specific functions to maintain the homeostasis of the skin. The dysregulation of ion channels plays a major role in the pathophysiology of psoriasis, affecting various aspects of epidermal cells, immune responses, and sensory neuron signaling. Impaired function of ion channels can lead to altered calcium signaling, inflammation, proliferation, and sensory signaling, all of which are central features of psoriasis. This overview summarizes the pathophysiological roles of ion channels in epidermal cells, immune cells, and sensory neurons during early and late psoriatic processes, thereby contributing to a deeper understanding of ion channel involvement in the interplay of psoriasis and making a crucial advance toward more precise and personalized approaches for psoriasis treatment.
The importance of hydraulic conditions in determining ecological equilibrium in Lake Tovel, Italy

Oligotrophic Lake Tovel is famous for its past bloodred Glenodinium sanguineum summer algal blooms in the 'Red Bay'. A unique feature ofthe lake is its dynamic water regime; BALDI (1941) considered the Iake to be fluvial-lacustrine. The area 's catchment is pseudokarstic, and the main surface inflow disappears about I km from the lake into a porous aquifer feeding the perilittoral springs in the Red Bay (Fig.l ). High catchment-to-lake-area ratio, together with high mean elevation, contributes to fast water renewal in spring and early summer concomitant with snow melt. The aquifer's volume (> 50% lake volume), guarantees a continuous inflow of cold (-5 0 C) water to the lake; however, in very dry periods inflow does not compensate outflow, causing a decrease in lake Ievel, particularly evident in the Red Bay (FERRETTI & BORSATO 2004).
Runtime Systems for Parallel Architectures

research approaches indeed allowed for a much better reuse of runtime systems within different programming environments. The µ PM 2 platform has, for instance, been successfully used as a basis for implementing a distributed Java virtual machine [1], a Corba object broker [53], a high-performance communication framework for grids (PadicoTM [48]) and even a multi-network version of the MPICH [7], [6] library.
Learning Opening Strategy in the Game of Go

In this paper, we present an experimental methodology and results for a machine learning approach to learning opening strategy in the game of Go, a game for which the best computer programs play only at the level of an advanced beginning human player. While the evaluation function in most computer Go programs consists of a carefully crafted combination of pattern matchers, expert rules, and selective search, we employ a neural network trained by self-play using temporal difference learning. Our focus is on the sequence of moves made at the beginning of the game. Experimental results indicate that our approach is effective for learning opening strategy, and they also identify higherlevel features of the game that improve the quality of the learned evaluation function.