Miracle-dz/UniFAR-FTUs huggingface dataset:
Subretinal Transplantation of Human Central Nervous System Stem Cells Stimulates Controlled Proliferation of Endogenous Retinal Pigment Epithelium

Purpose The loss of retinal pigment epithelial (RPE) cells is a feature common to age-related macular degeneration (AMD) and retinitis pigmentosa (RP) and multiple early phase clinical trials are underway testing the safety of RPE cell replacement for these diseases. We examined whether transplantation of human neural stem cells into the subretinal space could enhance the endogenous proliferative capacity of the host RPE cell to regenerate. Methods Human central nervous system stem cells (HuCNS-SC) were isolated from enzymatically treated brain tissue using flow cytometry. Pigmented dystrophic Royal College of Surgeons (RCS) and S334ter-4 rats treated with oral bromodeoxyuridine (BrdU) received a unilateral subretinal injection of 1.0 × 105 HuCNS-SC cells at either postnatal day 21 or 60. Animals were sacrificed at 90, 120, and 150 days of age. Eyes were fixed processed for cryostat sectioning. Sections were immunostained with Stem101, Ku80, RPE65, OTX1/2, BrdU, and CRALBP antibodies and analyzed via confocal microscopy. Results RCS rats that received transplantation of HuCNS-SC had significantly more (approximately 3-fold) Ki67-positive or BrdU-labelled host RPE cells adjacent to the HuCNS-SC graft than controls. Significantly increased host RPE cell proliferation as a result of HuCNS-SC transplantation also was confirmed in S334ter-line 4 transgenic rats with higher proliferation observed in animals with longer posttransplantation periods. Conclusions These results suggest that controlled proliferation of endogenous RPE by HuCNS-SC may provide another mechanism by which RPE cell diseases could be treated. Translational Relevance Engaging the capacity for endogenous RPE cell regeneration in atrophic diseases may be a novel therapeutic strategy for degenerative diseases of the RPE and retina.
In vitro stability of B-type natriuretic peptide (BNP) in plasma stored under different conditions when measured with the Lumipulse® assay

Abstract Natriuretic peptides are a laboratory tool with significant implications for the diagnosis and prognosis of heart failure (HF). The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommended that assays must be examined for sample stability because there appears to be assay dependent. We aimed to evaluate the in vitro stability of B-type natriuretic peptide (BNP) under different handling conditions and using a BNP assay from Fujirebio Diagnostics (Tokyo, Japan). BNP concentrations were measured in plasma EDTA samples from 11 subjects to evaluate the in vitro stability at room temperature and at 4 °C and in 10 subjects to check the in vitro stability of samples stored at –20 °C during 1 and 3 months. Stability limit was defined according to Spanish Society of Laboratory Medicine (SEQC-ML) recommendations. At room temperature and 4 °C, BNP concentrations decreased progressively in samples collected in both groups, remaining stable within four hours from collection. BNP concentrations also were stable within four hours from collection in whole blood at room temperature. Finally, at –20 °C, BNP concentrations remained stable in both groups at 1 and 3 months, respectively. According to our results, BNP, stored at room temperature or at 4 °C, should be assayed in the first four hours after collection. Besides, BNP was shown to be stable in whole blood for at least four hours at room temperature. If the testing cannot be performed within the first four hours, the plasma should be frozen and kept at –20 °C for up to 3 months.
Metal Slot Color Filter Based on Thin Air Slots on Silver Block Array

The human eye perceives the color of visible light depending on the spectrum of the incident light. Hence, the ability of color expression is very important in display devices. For practical applications, the transmitted color filter requires high transmittance and vivid colors, covering full standard default color spaces (sRGB). In this paper, we propose a color filter with a silver block array on a silica substrate structure with nanoscale air slots where strong transmission is observed through the slots between silver blocks. We investigated the transmitted color by simulating the transmission spectra as functions of various structure parameters. The proposed structure with an extremely small pixel size of less than 300 nm covers 90% of sRGB color depending on the structure and has a narrow angular distribution of transmitted light.
Stroke After Coronary Artery Bypass Grafting and Percutaneous Coronary Intervention: Incidence, Pathogenesis, and Outcomes

S troke is a devastating complication of both coronary artery bypass grafting (CABG) surgery and percutaneous coronary intervention (PCI). In a recent survey of 3112 cardiac patients by Sun and colleagues, death or prolonged hospital-ization and long-term disability due to stroke was identi ﬁ ed as the main concerns of patients undergoing invasive procedures. 1 Better understanding of the prevalence of stroke and its acute and long-term sequelae by both physicians and patients may have important implications for the choice of a particular revascularization strategy. after recommendations decision
High Aspect Ratio β-Ga2O3 Fin Arrays with Low-Interface Charge Density by Inverse Metal-Assisted Chemical Etching.

β-Ga2O3, with a bandgap of ∼4.6-4.9 eV and readily available bulk substrates, has attracted tremendous interest in the wide bandgap semiconductor community. Producing high aspect ratio β-Ga2O3 3D nanostructures without surface damage is crucial for next-generation power electronics. However, most wet etching methods can only achieve very limited aspect ratios, while dry etch usually damages the surface due to high energy ions. In this work, we demonstrate the formation of β-Ga2O3 fin arrays on a (010) β-Ga2O3 substrate by metal-assisted chemical etching (MacEtch) with high aspect ratio and sidewall surfaces with excellent quality. The etching was found to be strongly crystal orientation dependent, and three kinds of vertical structures were formed after MacEtch. The Schottky barrier height (SBH) between Pt and various MacEtch-produced β-Ga2O3 surfaces and sidewalls was found to decrease as the aspect ratio of the β-Ga2O3 vertical structure increased. This could be attributed to the different amount of oxygen lost at the surface after etching, as indicated by the XPS and TEM examination. Very little hysteresis was observed in the capacitance-voltage characteristics for the 3D Pt/Al2O3/β-Ga2O3 MOS capacitor structures, and the extracted interface trap density was as small as 2.73 × 1011 cm-2 eV-1, comparable to or lower than that for unetched planar β-Ga2O3 surfaces.
Tandem 13-Lipoxygenase Genes in a Cluster Confers Yellow-Green Leaf in Cucumber

Some lipoxygenase (LOX) isoenzymes can co-oxidize carotenoids. Carotenoids are collectors of light energy for photosynthesis and can protect plants from reactive oxygen species and coloration. This study isolated the cucumber (Cucumis sativus L.) yellow-green leaf mutant (ygl1), which had yellow-green leaves with decreased chlorophyll synthesis, increased relative carotenoid content, and delayed chloroplast development. Genetic analysis demonstrated that the phenotype of ygl1 was caused by a recessive mutation in a nuclear gene. The bulked segregants were resequenced, and the candidate ygl1 locus identified was mapped to the 9.2 kb region of the chromosome 4. Sequence analysis revealed that ygl1 encodes the tandem 13-LOX genes in a cluster. Four missense mutations were found in four tandem 13-LOX genes (Csa4M286960, Csa4M287550, Csa4M288070, and Csa4M288080) in the ygl1 mutant, and the four 13-LOX genes showed high similarity with one another. The transient RNA interference and virus-induced gene silencing of these genes simultaneously resulted in yellow-green leaves with a reduced amount of chloroplasts and increased relative carotenoid content, which were observed in the ygl1 mutant. This evidence supported the non-synonymous SNPs (Single Nucleotide Polymorphism) in the four tandem 13-LOX genes as being the causative mutation for the yellow-green leaves. Furthermore, this study provides a new allele for breeding cucumbers with yellow-green leaves and serves as an additional resource for studying carotenoid biosynthesis.
Different functional roles for K+ channel subtypes in regulating small intestinal glucose and ion transport

ABSTRACT Although K+ channels are important in mediating the driving force for colonic ion transport, their role in small intestinal transport is poorly understood. To investigate this, small intestinal short circuit currents (Isc) and HCO3− secretion were measured in mice, and intracellular pH (pHi) was measured in small intestinal epithelial SCBN cells. The expression and location of Kv subtypes were verified by RT-PCR, western blotting and immunohistochemistry. Diabetic mice were also used to investigate the role of Kv subtypes in regulating intestinal glucose absorption. We found that KV7.1 is not involved in duodenal ion transport, while KCa3.1 selectively regulates duodenal Isc and HCO3− secretion in a Ca2+-mediated but not cAMP-mediated manner. Blockade of KCa3.1 increased the rate of HCO3− fluxes via cystic fibrosis transmembrane conductance regulator (CFTR) channels in SCBN cells. Jejunal Isc was significantly stimulated by glucose, but markedly inhibited by 4-aminopyridine (4-AP) and tetraethylammonium (TEA). Moreover, both Kv1.1 and Kv1.3 were expressed in jejunal mucosae. Finally, 4-AP significantly attenuated weight gain of normal and diabetic mice, and both 4-AP and TEA significantly lowered blood glucose of diabetic mice. This study not only examines the contribution of various K+ channel subtypes to small intestinal epithelial ion transport and glucose absorption, but also proposes a novel concept for developing specific K+ channel blockers to reduce weight gain and lower blood glucose in diabetes mellitus. Summary: This study examines the different functions of various K+ channel subtypes in small intestinal epithelial, which proposes a novel concept for the development of weight-loss drugs and hypoglycemic drugs.
Factors associated with the identification of child mental health problems in primary care—a systematic review

Abstract Background: Although common and often with long-lasting effects, child mental health problems (MHPs) are still under-recognized and under-treated. A better understanding of the factors associated with the identification of MHPs in primary care may improve the recognition of MHPs. Objectives: To review studies on factors associated with the identification of child MHPs in primary care. Methods: Six leading databases were systematically searched until 1 October 2018. Two independent researchers selected articles and extracted data on study characteristics and factors associated with MHP identification. Inclusion criteria were the investigation of factors associated with MHP identification by primary care professionals (PCPs) in children aged 0–18 years. Results: Of the 6215 articles identified, 26 were included. Prevalence rates of PCP-identified MHPs varied between 7 and 30%. PCPs identified 26–60% of children with an increased risk of MHPs as indicated by MHP assessment tools, but associated factors were investigated in relatively few studies. MHPs were more often identified in children with a family composition other than married parents, with worse mental health symptoms, prior MHPs, among boys in elementary school, when contact with PCPs was related to parental psychosocial concerns or routine health check-ups, when PCPs were recently trained in MHPs or when PCPs felt less burdened treating MHPs. Conclusion: MHP identification varied substantially between studies and PCPs and was related to several child, family and practice factors. Future studies should systematically investigate factors associated with MHP identification by PCPs and specifically in children with an increased risk of MHPs according to mental health assessment tools.
Optimization of surgical intervention outside the epileptogenic zone in the Virtual Epileptic Patient (VEP)

Studies to improve the efficacy of epilepsy surgery have focused on better refining the localization of the epileptogenic zone (EZ) with the aim of effectively resecting it. However, in a considerable number of patients, EZs are distributed across multiple brain regions and may involve eloquent areas that cannot be removed due to the risk of neurological complications. There is a clear need for developing alternative approaches to induce seizure relief, but minimal impact on normal brain functions. Here, we develop a personalized in-silico network approach, that suggests effective and safe surgical interventions for each patient. Based on the clinically identified EZ, we employ modularity analysis to identify target brain regions and fiber tracts involved in seizure propagation. We then construct and simulate a patient-specific brain network model comprising phenomenological neural mass models at the nodes, and patient-specific structural brain connectivity using the neuroinformatics platform The Virtual Brain (TVB), in order to evaluate effectiveness and safety of the target zones (TZs). In particular, we assess safety via electrical stimulation for pre- and post-surgical condition to quantify the impact on the signal transmission properties of the network. We demonstrate the existence of a large repertoire of efficient surgical interventions resulting in reduction of degree of seizure spread, but only a small subset of them proves safe. The identification of novel surgical interventions through modularity analysis and brain network simulations may provide exciting solutions to the treatment of inoperable epilepsies.
A T164S mutation in the dengue virus NS1 protein is associated with greater disease severity in mice

The T164S mutation in the NS1 protein of dengue virus increases disease severity in mice through complement activation. Molecular insights into dengue virus NS1 Several hundred thousand cases of severe dengue disease occur annually worldwide. Using phylogenetic analysis of publicly available dengue virus sequences, Chan et al. now show that the T164S mutation in the dengue virus NS1 protein correlated with severe dengue epidemics in the Americas. The investigators reverse engineered this mutation into the NS1 protein of a dengue virus serotype 2 mildly infectious strain. The resulting T164S mutant dengue virus produced more secreted NS1 than wild-type virus in infected mammalian cell lines, mosquitoes, and mice. Gene expression analysis and direct measurement of factors promoting disease severity in mice revealed an association between the T164S mutation in NS1 and its lipoprotein structure. Dengue viruses cause severe and sudden human epidemics worldwide. The secreted form of the nonstructural protein 1 (sNS1) of dengue virus causes vascular leakage, a hallmark of severe dengue disease. Here, we reverse engineered the T164S mutation of NS1, associated with the severity of dengue epidemics in the Americas, into a dengue virus serotype 2 mildly infectious strain. The T164S mutant virus decreased infectious virus production and increased sNS1 production in mammalian cell lines and human peripheral blood mononuclear cells (PBMCs) without affecting viral RNA replication. Gene expression profiling of 268 inflammation-associated human genes revealed up-regulation of genes induced in response to vascular leakage. Infection of the mosquito vector Aedes aegypti with the T164S mutant virus resulted in increased viral load in the mosquito midgut and higher sNS1 production compared to wild-type virus infection. Infection of type 1 and 2 interferon receptor–deficient AG129 mice with the T164S mutant virus resulted in severe disease coupled with increased complement activation, tissue inflammation, and more rapid mortality compared to AG129 mice infected with wild-type virus. Molecular dynamics simulations predicted that mutant sNS1 formed stable dimers similar to the wild-type protein, whereas the hexameric mutant sNS1 was predicted to be unstable. Immunoaffinity-purified sNS1 from T164S mutant virus–infected mammalian cells was associated with different lipid classes compared to wild-type sNS1. Treatment of human PBMCs with sNS1 purified from T164S mutant virus resulted in a twofold higher production of proinflammatory cytokines, suggesting a mechanism for how mutant sNS1 may cause more severe dengue disease.
AMPAR Palmitoylation Tunes Synaptic Strength: Implications for Synaptic Plasticity and Disease

The addition of lipid moieties to proteins has been studied for nearly 40 years ([Folch and Lees, 1951][1]; [Kamiya et al., 1978][2]; [Schmidt et al., 1979][3]; [Carr et al., 1982][4]), but the scope and diversity of functional consequences are still being investigated. This is particularly true for
Quality of leadership and presenteeism in health professions education and research: a test of a recovery-based process model with cognitive irritation and impaired sleep as mediators

ABSTRACT Presenteeism (PRES) includes working while feeling ill and constrained in performance. Compared with absence from work, PRES generates signiﬁcantly higher cost estimates. Health problems and PRES are related to leadership quality. Hence, research on corporate health management needs to explore why leadership problems (LP) correspond to more frequent PRES. This study tests recovery after work as an underlying process with cognitive irritation (COGIRR) and sleep problems (SP) as simultaneous mediators and explores three mediation pathways (path one: LP→COGIRR→PRES; path two: LP→SP→PRES; and path three: LP→COGIRR→SP→PRES). Out of 293 employees of a university’s school of health professions in German-speaking Switzerland, 211 completed a questionnaire. LP and PRES were found to be positively related (r(211) = . 22, p < . 01). The tests of mediation yielded no signiﬁcant results for path one and two, but the third mediation path LP→COGIRR→SP→PRES was positive and diﬀered signiﬁcantly from zero (B = 0.83, CI95 = 0.33 to 1.69). According to our results, a recovery-based mediation model ﬁts the empirical self-report data best. These results suggest that occupational health interventions should improve leadership quality to promote recovery after work in order to increase health and productivity by reduced PRES.
Prevalence and predictors of probable depression in prostate cancer survivors

The early diagnosis and treatment of depression are cancer care priorities. These priorities are critical for prostate cancer survivors because men rarely seek mental health care. However, little is known about the epidemiology of depression in this patient population. The goal of this study was to describe the prevalence and predictors of probable depression in prostate cancer survivors.
Bilobalide protects astrocytes from oxygen and glucose deprivation‐induced oxidative injury by upregulating manganese superoxide dismutase

Bilobalide (BB), a constituent of the Ginkgo biloba extract, is a neuroprotective agent with multiple mechanisms of action. To further explore the potential therapeutic effects of BB in stroke, we investigated its effects on primary astrocytes using the oxygen and glucose deprivation‐reoxygenation (OGD‐R) model. Cell viability was measured by lactate dehydrogenase release assay and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Cell death was measured by annexin 5 conjgated with fluorescein isothiocyanate (V‐FITC) assay, and reactive oxygen species (ROS) production was measured by 2′,7′‐Dichlorodihydrofluorescein Diacetate (DCFH‐DA) probe. Manganese superoxide dismutase (MnSOD) expression was measured by western blot and immunofluorescence. Mitochondrial membrane potential was monitored using JC‐1 staining. Our results show that OGD‐R downregulated MnSOD and impaired mitochondrial function, which further enhanced ROS production in primary astrocytes. As a result, cell viability was compromised, and cell death increased. BB treatment protected astrocytes from those injuries mainly by restoring MnSOD level as MnSOD inhibitor abolished the effects of BB. In conclusion, we demonstrated that OGD‐R induced astrocytic injury, but BB increased the expression of MnSOD, the ROS scavenger, to reverse the exacerbated astrocytic injury.
Approximating Friction Factors for Trickle Tubing

A continuous functional form is identified which can represent explicitly the observed relationships between Reynolds number and friction factor for trickle irrigation tubing. Two methods are examined for determining a specific function of the chosen form from empirical data: a numerical analytic technique based on least-squared errors and Newton's method and an interactive computer graphics technique. The proposed methods are illustrated using data for a common type and size of trickle irrigation tubing.
A broadly neutralizing germline-like human monoclonal antibody against dengue virus envelope domain III

Dengue is the most widespread vector-borne viral disease caused by dengue virus (DENV) for which there are no safe, effective drugs approved for clinical use. Here, by using sequential antigen panning of a yeast antibody library derived from healthy donors against the DENV envelop protein domain III (DIII) combined with depletion by an entry defective DIII mutant, we identified a cross-reactive human monoclonal antibody (mAb), m366.6, which bound with high affinity to DENV DIII from all four DENV serotypes. Immunogenetic analysis indicated that m366.6 is a germline-like mAb with very few somatic mutations from the closest VH and Vλ germline genes. Importantly, we demonstrated that it potently neutralized DENV both in vitro and in the mouse models of DENV infection without detectable antibody-dependent enhancement (ADE) effect. The epitope of m366.6 was mapped to the highly conserved regions on DIII, which may guide the design of effective dengue vaccine immunogens. Furthermore, as the first germline-like mAb derived from a naïve antibody library that could neutralize all four DENV serotypes, the m366.6 can be a tool for exploring mechanisms of DENV infection, and is a promising therapeutic candidate.
Relationship between Nutrition and Alcohol Consumption with Blood Pressure: The ESTEBAN Survey

Background: Dietary interventions are recommended for the prevention of hypertension. The aim of this study was to evaluate and quantify the relationship between alcohol consumption and the DASH (Dietary Approaches to Stop Hypertension) score with blood pressure (BP) stratified by gender. Methods: Cross-sectional analyses were performed using data from 2105 adults from the ESTEBAN survey, a representative sample of the French population. Pearson correlation analyses were used to assess the correlation between the DASH score and alcohol with BP. Regressions were adjusted by age, treatment, socio-economic level, tobacco, exercise, Body mass index (BMI), and cardiovascular risk factors and diseases. Results: The DASH score was negatively correlated with systolic (SBP) and diastolic BP (DBP) (p < 0.0001). Alcohol was positively associated with increased BP only in men. The worst quintile of the DASH score was associated with an 1.8 mmHg increase in SBP and an 0.6 mmHg increase in SBP compared to the greatest quintile in men and with a 1.5 mmHg increase in SBP and an 0.4 mmHg increase in SBP in women. Male participants in the worst quintile of alcohol consumption showed an increase of 3.0 mmHg in SBP and 0.8 mmHg in DBP compared to those in the greatest quintile. Conclusion: A high DASH score and a reduction in alcohol consumption could be effective nutritional strategies for the prevention of hypertension.