gebhart/patrepeval huggingface dataset:
NKX2-5 Mutations in an Inbred Consanguineous Population: Genetic and Phenotypic Diversity (2015)

NKX2-5 mutations are associated with different forms of congenital heart disease. Despite the knowledge gained from molecular and animal studies, genotype-phenotype correlations in humans are limited by the lack of large cohorts and the incomplete assessment of family members. We hypothesized that studying the role of NKX2-5 in inbred populations with homogeneous genetic backgrounds and high consanguinity rates such as Lebanon could help closing this gap. We sequenced NKX2-5 in 188 index CHD cases (25 with ASD). Five variants (three segregated in families) were detected in eleven families including the previously documented p.R25C variant, which was found in seven patients from different families, and in one healthy individual. In 3/5 familial dominant ASD cases, we identified an NKX2-5 mutation. In addition to the heterogeneity of NKX2-5 mutations, a diversity of phenotypes occurred within the families with predominant ASD and AV block. We did in fact identify a large prevalence of Sudden Cardiac Death (SCD) in families with truncating mutations, and two patients with coronary sinus disease. NKX2-5 is thus responsible for dominant familial ASD even in consanguineous populations, and a wide genetic and phenotypic diversity is characteristic of NKX2-5 mutations in the Lebanese population.
Endovascular therapeutic hypothermia adjunctive to percutaneous coronary intervention in acute myocardial infarction: realistic simulation as a game changer (2022)

gov: NCT02664194.
Limits of 4 Wires 3 Levels NPC topology for Hybrid Energy Storage System and power quality improvement in weak grids (2016)

International audience
Prospective comparative study between knee alignment-oriented static and dynamic balance exercise in patellofemoral pain syndrome patients with dynamic knee valgus (2022)

Exercise therapy has been reported as an effective treatment method for patellofemoral pain syndrome (PFPS). However, there is a lack of studies regarding the effectiveness of balance exercise in the treatment of patients with PFPS. This study aimed to prospectively compare changes in proprioception, neuromuscular control, knee muscle strength, and patient-reported outcomes between patients with PFPS treated with knee alignment-oriented static balance exercise (SBE) and dynamic balance exercise (DBE). The participants were divided into 2 groups: 17 knee alignment-oriented SBE group and 19 knee alignment-oriented DBE group. Proprioception was assessed by dynamic postural stability using postural stabilometry. Neuromuscular control and knee muscle strength were measured for acceleration time and peak torque in quadriceps muscle using an isokinetic device. Patient-reported outcomes were evaluated using a visual analog scale for pain and the Kujala Anterior Knee Pain Scale. There was greater improvement in dynamic postural stability (0.9 ± 0.3 vs 1.2 ± 0.5; 95% confidence interval [CI]: 0, 0.6; Effect size: 0.72; P = .021) and quadriceps AT (40.5 ± 14.3 vs 54.1 ± 16.9; 95% CI: 2.9, 24.2; Effect size: 0.86; P = .014) in the DBE group compared to the SBE group. Knee alignment-oriented DBE can be more effective in improving dynamic postural stability and quadriceps muscle reaction time compared with the knee alignment-oriented SBE in PFPS patients with dynamic knee valgus.
Articular Cartilage Repair Techniques (2016)

Articular cartilage defects of the knee are common among athletes and the general population in which the physical demands of sport and activity result in significantly acute and chronic stresses on joints. Chondral defects are associated with pain and functional impairment, which limit sporting participation and may progress to joint degeneration and frank arthritis. These lesions have limited intrinsic healing ability due to the avascular nature of the cartilage and the unfavorable mechanical environment for spontaneous repair within joints. The ultimate goal is prevention of injury, chondropenia, and the progression of arthritis. Management of established chondral lesions aims to allow athletes to return to high-impact sports and can be considered in terms of protection of existing cartilage, chondrofacilitation, and resurfacing. Repaired and/or regenerated cartilage must closely resemble and function like normal hyaline cartilage, and this ability may be the most significant factor for the return to sport. In this very comprehensive review utilizing experts’ opinions, we explore the recent advances in epidemiology, classification, pathoanatomy, and clinical assessment in athletes. In this group with chondral and bone injury and articular defects, early osteoarthritis, we compare the relative merits and outcomes of established and emerging forms of treatment. This is a contemporary compendium of concepts and technology that will serve as a resource for today’s clinicians, clinical and basic scientists, and training professionals.
BIOL-08. RADIATION DRIVES METASTASIS IN MEDULLOBLASTOMA THROUGH AN INFLAMMATORY PROCESS (2023)

Abstract Current treatment for medulloblastoma is comprised of surgery, radiotherapy (RT) and/or chemotherapy. Although the primary tumor is controlled with this approach, recurrent metastatic disease is ubiquitously fatal. However, little is known about the biology of metastatic recurrences in medulloblastoma. In the present study, we observe across 3 non-overlapping cohorts of infant medulloblastoma that patients recur locally without focal RT and metastatically after focal RT. Using 3 independent murine flank xenograft medulloblastoma models, we found that the incidence of leptomeningeal metastasis was significantly increased in mice that received RT compared to sham controls. We have also found a significant increase in viable circulating tumor cells after RT. Our multi-omics (bulk RNA-seq, scRNA-seq and proteo/phosphoproteomics) approach using immunocompetent sporadic medulloblastoma models treated with RT showed activation of the innate inflammatory response through the overexpression of chemokines, cytokines and activation of immune cell types. In situ analysis of protein expression after RT showed a gradual increase in the abundance of macrophages, neutrophils and dendritic cells after RT, suggesting increased permeability and cell trafficking across the blood brain barrier. Applying live intravital microscopy using a low molecular weight vascular dye (150kDa), we observed a striking increase in blood vessel permeability in RT vs sham-treated brain tumors. Our observations support a model where RT drives metastasis through inflammation. To test this, we applied lipopolysaccharide (LPS), an inflammation inducing treatment, to a sporadic murine medulloblastoma model which significantly increased the metastatic burden. We then treated a xenograft model with dexamethasone in combination with RT, which resulted in total abrogation of metastatic dissemination compared to RT alone. Collectively, our findings suggest that while external beam irradiation is an effective and essential treatment for medulloblastoma, it may facilitate metastatic dissemination through an inflammation-induced process. These findings can help inform potential approaches to prevent disseminated relapsed disease.
Characterisation of the mechanical failure and fracture mechanisms of single grain Y–Ba–Cu–O bulk superconductors (2019)

Abstract The widespread use of melt processed, single grain (RE)–Ba–Cu–O bulk superconductors [(RE)BCO], where RE = Y, Gd or Sm, is limited predominantly by the poor mechanical properties of these inherently brittle, ceramic-like materials. The high density of flaws, such as cracks and voids, within the single grain microstructure leads directly to a low fracture toughness. As a result, the Lorentz forces, generated when these materials carry current in the presence of a large magnetic field, create stresses sufficiently large to cause brittle failure. The addition of Ba–Cu–O (liquid phase) and Ag to the precursor composition prior to melt-growth has been demonstrated to be effective in improving the mechanical properties of these technologically important materials. In this work, we characterise the mechanical failure of single grain YBCO bulk superconductors in terms of a Weibull statistical distribution. In addition, differences in fracture mechanisms have been studied to provide a better understanding of how the provision of additional liquid phase and silver produces YBCO single grains with better resulting mechanical properties and how these can be improved further.
Advanced Optical Modulators Using Silica-LiNbO3 Hybrid Configuration (2012)

We review optical modulators with a hybrid configuration of silica PLCs and LiNbO3 phase modulators. The hybrid configuration is highly scalable for advanced modulation formats, and is reliable both thermally and mechanically.
Defocus Incorporated Soft Contact (<scp>DISC</scp>) lens (2015)

Summary Purpose DISC lens is a concentric bifocal contact lens, combining myopia correction and constant myopic defocus. We investigate the effects of wearing time, eye dominance and pupil size on myopia control with DISC lens. Methods 128 children completed a 2‐year double masked randomized clinical trial of myopic control (65 in DISC lens and 63 in single vision contact lenses). Refraction and axial length were measured with cylcoplegic autorefraction and IOL Master. Ocular dominance was determined with the Miles and Porta tests. Pupil images were captured by EAS ‐1000 (Nidek) for children wearing the DISC lens, the area ratio of the two optical zones was then calculated. Results Those who have worn the DISC lens for 8 hours daily reached a 60% reduction in myopia progression. There were no significant differences in eye dominance with refractive changes (t‐test), association between myopic progression (chi‐square test) and correlation between the zones ratio at pupil and myopic progression (multiple linear regression analysis). Conclusions We identified a dosage effect on the DISC lens in slowing myopia progression. Ocular dominance and pupil size do not have any effect on myopia control using the DISC lens.
A glycogene mutation map for discovery of diseases of glycosylation (2014)

Glycosylation of proteins and lipids involves over 200 known glycosyltransferases (GTs), and deleterious defects in many of the genes encoding these enzymes cause disorders collectively classified as congenital disorders of glycosylation (CDGs). Most known CDGs are caused by defects in glycogenes that affect glycosylation globally. Many GTs are members of homologous isoenzyme families and deficiencies in individual isoenzymes may not affect glycosylation globally. In line with this, there appears to be an underrepresentation of disease-causing glycogenes among these larger isoenzyme homologous families. However, genome-wide association studies have identified such isoenzyme genes as candidates for different diseases, but validation is not straightforward without biomarkers. Large-scale whole-exome sequencing (WES) provides access to mutations in, for example, GT genes in populations, which can be used to predict and/or analyze functional deleterious mutations. Here, we constructed a draft of a functional mutational map of glycogenes, GlyMAP, from WES of a rather homogenous population of 2000 Danes. We cataloged all missense mutations and used prediction algorithms, manual inspection and in case of carbohydrate-active enzymes family GT27 experimental analysis of mutations to map deleterious mutations. GlyMAP (http://glymap.glycomics.ku.dk) provides a first global view of the genetic stability of the glycogenome and should serve as a tool for discovery of novel CDGs.
Abnormal apoptosis and cell cycle progression in humans exposed to methyl tertiary-butyl ether and benzene contaminating water (1997)

1. In this study we hypothesized that in individuals with certain genetic makeup, MTBE, benzene or their metabolites act as adducts and may induce programmed cell death. 2. Our study involved a group of 60 male and female subjects who were exposed to MTBE and benzene-contaminated water concentrations up to 76 PPB for MTBE and 14 PPB for benzene, for a period of 5 to 8 years. For comparison, we recruited a control group consisting of 32 healthy males and females with similar age distribution and without a history of exposure to MTBE or benzene. 3. Peripheral blood lymphocytes (PBL) of both groups were tested for the percentage of apoptotic cells and cell cycle progression using flow cytometry. 4. When apoptotic lymphocytes from exposed individuals were compared to apoptotic lymphocytes from the control group, statistically-significant differences between each mean group were detected (26.4 +/- 1.8 and 12.1 +/- 1.3, respectively), indicating an increased rate of apoptosis in 80.5% of exposed individuals (P < 0.0001, Mann-Whitney U-Test). MTBE and benzene-induced apoptosis is attributed to a discrete block within the cell cycle progression. Because cell cycle analysis showed that in PBL from chemically-exposed individuals, between 20-50% of cells were accumulated at the S-G2/M boundaries. 5. One of the signaling molecules which mediates programmed cell death is nuclear factor Kappa-B (NF-kappa B). NF-kappa B was examined as one of the many molecular mechanisms for mediating cell death by MTBE and benzene. Indeed, addition of inhibitors of NF-kappa B activation pyrrolidine dithiocarbamate (PDTC), to the lymphocytes of the chemically-exposed group was capable of inhibiting programmed cell death by 40%. This reversal of apoptosis almost to the control level by inhibitor of NF-kappa B activation may indicate involvement of this signaling molecule in MTBE and benzene induction of programmed cell death.
Tools for Surface Treatment of Silicon Planar Intracortical Microelectrodes (2022)

Intracortical microelectrodes hold great therapeutic potential. But they are challenged with significant performance reduction after modest implantation durations. A substantial contributor to the observed decline is the damage to the neural tissue proximal to the implant and subsequent neuroinflammatory response. Efforts to improve device longevity include chemical modifications or coating applications to the device surface to improve the tissue response. Development of such surface treatments is typically completed using non-functional "dummy" probes that lack the electrical components required for the intended application. Translation to functional devices requires additional consideration given the fragility of intracortical microelectrode arrays. Handling tools greatly facilitate surface treatments to assembled devices, particularly for modifications that require long procedural times. The handling tools described here are used for surface treatments applied via gas-phase deposition and aqueous solution exposure. Characterization of the coating is performed using ellipsometry and x-ray photoelectron spectroscopy. A comparison of electrical impedance spectroscopy recordings before and after the coating procedure on functional devices confirmed device integrity following modification. The described tools can be readily adapted for alternative electrode devices and treatment methods that maintain chemical compatibility.
Continuous Flow Processing of ZIF-8 Membranes on Polymeric Porous Hollow Fiber Supports for CO<sub>2</sub> Capture (2017)

We have utilized an environmentally friendly synthesis approach for the accelerated growth of a selective inorganic membrane on a polymeric hollow fiber support for postcombustion carbon capture. Specifically, continuous defect-free ZIF-8 thin films were grown and anchored using continuous flow synthesis on the outer surface of porous supports using water as solvent. These membranes demonstrated CO<sub>2</sub> permeance of 22 GPU and the highest reported CO<sub>2</sub>/N<sub>2</sub> selectivity of 52 for a continuous flow synthesized ZIF-8 membrane.
Abstract WP430: Endothelial Cell Collection from Ipsilateral Middle Cerebral Artery in Acute Ischemic Stroke (2017)

Introduction: The cerebrovascular endothelium plays a critical role in the pathogenesis of and response to acute ischemic stroke (AIS). To date, techniques to study its function have relied on animal and in vitro models. A robust method of endothelial cell (EC) capture in patients with AIS at early time points, from within the ischemic region, could greatly advance our understanding of cerebrovascular injury. Method: Patients undergoing thrombectomy for middle cerebral artery occlusion (MCA) within 8 hours of onset were offered enrollment if the pass of their stent-retriever device occurred directly into a distal access catheter in the proximal M1 segment, limiting exposure of the device to only the MCA. After retrieval, ECs adherent to the devices were retrieved and stained for EC (CD31) and leukocyte (CD45) markers. EC identity and yield were confirmed by flow cytometry with simultaneous immuno-fluorescence microscopy. Cultured human ECs were used as positive controls. The EC fraction was defined as CD31 + CD45 - with size and morphological features consistent with the positive controls. Results: ECs from stent-retriever devices (n=3) were collected and pooled. Approximately 8% of the collected cells represented ECs. EC collected from the stent-retrievers demonstrated highly similar shape, morphology and antibody staining patterns compared to the positive controls (Figure). Conclusions: Here we provide the first demonstration of a rapid post-thrombectomy method for reliable harvesting of cerebral ECs in humans. The ability to capture these cells in patients with AIS within hours of symptom onset opens many avenues of exploration for determining the role of ECs in AIS.
EVALUATING OPTIONS FOR LARGE-SCALE WATERSHED REMEDIATION (2010)

Monday Creek of the Hocking River has a 300 km 2 drainage basin in southeastern Ohio, and since the middle of the 19th century, extensive portions of the watershed have been subjected to underground and surface coal mining. A recent survey of the watershed has identified over 4,300 point sources of acid mine drainage which have rendered a number of stream reaches within the watershed sterile and unable to support diverse, aquatic life. In 2003, Dr. Stiles developed a model of those aspects of water quality related to Acid Mine Drainage (AMD) for the watershed using the TAMDL computer program developed at West Virginia University. The computer program TAMDL was designed to model stream water quality in watersheds affected by AMD and its treatment by simulating the evolution of stream pH, net acidity, and the concentrations of aluminum, iron, and manganese. The Monday Creek TAMDL model was then employed by the authors to develop a cost effective strategy for the treatment of AMD in the watershed. Since the close of this project, several passive and active treatment systems have been installed in the Monday Creek watershed. The objective of this new project was to recalibrate the TAMDL model created in 2003 for the new conditions in the watershed and use this recalibrated model to design a revised cost effective treatment strategy to bring the water quality conditions from their current level up to the remediation target conditions. The remediation target conditions for the Monday Creek watershed were those minimum and maximum pH levels and maximum aluminum and iron concentrations that would allow aquatic life to be reestablished in the main stem.
Understanding of Ni(OH)<sub>2</sub>/ NiOOH Irreversible Phase Transformations: Ni<sub>2</sub>O<sub>3</sub>H Impact on Alkaline Batteries (2018)

A new ageing mode for positive electrode, associated to Ni2O3H formation, was observed for the first time in alkaline batteries (Ni-Cd, Ni-MH) during harsh shallow cycling operations. The study of Ni2O3H synthesis conditions outlined that γ-NiOOH and βIII-NiOOH phases display instability versus electrolyte at elevated temperature, leading to the irreversible formation of Ni2O3H through a reduction, followed by a dissolution / precipitation mechanism. It was shown also that Ni2O3H is a rather moderate electronic conductor and is almost electrochemically inactive, in good correlation with the loss of cell capacity. Highlighting NiOOH / Ni2O3H transformation provides a new understanding of nickel hydroxide and oxyhydroxide phase transformations diagram.
Potential for severe airway obstruction from pediatric retropharyngeal abscess (2017)

Retropharyngeal abscesses in the pediatric population can cause severe respiratory distress. We report a rare case of significant airway obstruction in a 14-month-old patient requiring rapid, emergent tracheotomy after attempts at endotracheal intubation by an experienced airway surgeon were unsuccessful. The patient was diagnosed with streptococcal pharyngitis 9 days prior to presentation to our facility and was being treated with amoxicillin. Prompt diagnosis, communication, and appropriate multidisciplinary airway management can lead to successful outcomes even in these severe cases.
Epidemiology and Etiology of Acute Infectious Neurologic Disease (AIND) in Singapore (P4.294) (2014)

OBJECTIVE To describe the etiology, epidemiology, clinical features, and outcomes of acute infectious neurologic disease (AIND) in Singapore and to improve diagnostic yield using advanced novel pathogen-discovery techniques. BACKGROUND In Asia and world-wide, the epidemiology and etiology of AIND remain largely unknown. The reasons include limitations in current diagnostics, difficulty in obtaining appropriate biological specimens and varying case definitions. DESIGN/METHODS We prospectively recruited all inpatients with AIND at our institutions, beginning December 2012. We recorded demographic, epidemiological, clinical, laboratory, microbiological, neuroimaging, treatment and outcome data. Biological specimens (acute and convalescent sera), CSF, saliva, stool, urine and oropharyngeal swabs were collected. Testing for novel pathogens was conducted using immunofluorescence, polymerase chain reaction (PCR), serology, and MassTag PCR. RESULTS As of July 2013, 37 patients (22 males; mean age 42.4 years [range 21 to 80]) were analysed (869 screened; 72 eligible; 1 withdrew). The commonest presenting symptoms were headache(78.4%), fever(73.0%), focal weakness(51.4%), confusion(18.9%), seizures(10.8%) and psychiatric(5.4%); the commonest signs were meningism(40.5%), encephalopathy(13.5%) and motor deficits(13.5%). Infectious etiologies were identified in 9 patients (6 viral [2 varicella-zoster virus, 2 enterovirus, 1 herpes simplex virus, 1 Japanese B], 2 bacterial and 1 tuberculosis); 22 patients had presumed infectious etiologies without microbiological diagnosis; 6 had non-infectious etiologies. Three patients were lost to follow-up; 1 died of non-infectious cause. Neuroimaging showing abnormalities suggestive of CNS infection was more likely seen with MRI (1/12 non-contrast and 12/25 contrast MRI brain vs 0/27 non-contrast and 1/3 contrast CT brain). MassTag assay picked up 1 positive test for TB and 4 patients with dengue seroconversion. Additional tests for novel pathogens is ongoing. CONCLUSIONS/RELEVANCE 24.3% of patients admitted to our institutions for AIND have identified infectious etiology, 59.5% had presumed infectious etiology and 16.2% had non-infectious etiology. MRI was superior to CT in detecting abnormalities. Our study demonstrates that, despite advanced molecular diagnostic testing, identification of AIND etiologies remains a considerable challenge.
Yb:CaF2 regenerative amplifier for broadband seed (2010)

International audience