Miracle-dz/UniFAR-FTUs huggingface dataset:
Benefit of Targeting a LDL (Low-Density Lipoprotein) Cholesterol <70 mg/dL During 5 Years After Ischemic Stroke

Supplemental Digital Content is available in the text. Background and Purpose— The TST trial (Treat Stroke to Target) evaluated the benefit of targeting a LDL (low-density lipoprotein) cholesterol of <70 mg/dL to reduce the risk of cardiovascular events in 2860 patients with ischemic stroke with atherosclerotic stenosis of cerebral vasculature or aortic arch plaque >4 mm, in a French and Korean population. The follow-up lasted a median of 5.3 years in French patients (similar to the median follow-up time in the SPARCL trial [Stroke Prevention by Aggressive Reduction in Cholesterol Level]) and 2.0 years in Korean patients. Exposure duration to statin is a well-known driver for cardiovascular risk reduction. We report here the TST results in the French cohort. Methods— One thousand seventy-three French patients were assigned to <70 mg/dL (1.8 mmol/L) and 1075 to 100±10 mg/dL (90–110 mg/dL, 2.3–2.8 mmol/L). To achieve these goals, investigators used the statin and dosage of their choice and added ezetimibe on top if needed. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization and vascular death. Results— After a median follow-up of 5.3 years, the achieved LDL cholesterol was 66 (1.69 mmol/L) and 96 mg/dL (2.46 mmol/L) on average, respectively. The primary end point occurred in 9.6% and 12.9% of patients, respectively (HR, 0.74 [95% CI, 0.57–0.94]; P=0.019). Cerebral infarction or urgent carotid revascularization following transient ischemic attack was reduced by 27% (P=0.046). Cerebral infarction or intracranial hemorrhage was reduced by 28% (P=0.023). The primary outcome or intracranial hemorrhage was reduced by 25% (P=0.021). Intracranial hemorrhages occurred in 13 and 11 patients, respectively (HR, 1.17 [95% CI, 0.53–2.62]; P=0.70). Conclusions— After an ischemic stroke of documented atherosclerotic origin, targeting a LDL cholesterol of <70 mg/dL during 5.3 years avoided 1 subsequent major vascular event in 4 (number needed to treat of 30) and no increase in intracranial hemorrhage. Registration— URL: https://www.clinicaltrials. gov; Unique identifier: NCT01252875.
TRPC Channels in Cardiac Plasticity

The heart flexibly changes its structure in response to changing environments and oxygen/nutrition demands of the body. Increased and decreased mechanical loading induces hypertrophy and atrophy of cardiomyocytes, respectively. In physiological conditions, these structural changes of the heart are reversible. However, chronic stresses such as hypertension or cancer cachexia cause irreversible remodeling of the heart, leading to heart failure. Accumulating evidence indicates that calcium dyshomeostasis and aberrant reactive oxygen species production cause pathological heart remodeling. Canonical transient receptor potential (TRPC) is a nonselective cation channel subfamily whose multimodal activation or modulation of channel activity play important roles in a plethora of cellular physiology. Roles of TRPC channels in cardiac physiology have been reported in pathological cardiac remodeling. In this review, we summarize recent findings regarding the importance of TRPC channels in flexible cardiac remodeling (i.e., cardiac plasticity) in response to environmental stresses and discuss questions that should be addressed in the near future.
Antibiotic use in children hospitalised with pneumonia in Central Vietnam

Background and objectives Excessive use of antibiotics has been noted in children with respiratory tract infections in Vietnam, but antibiotic use in hospitalised children is poorly documented. Antibiotic use and direct healthcare costs in children hospitalised with pneumonia in central Vietnam were assessed. Methods A prospective descriptive study of children under 5 years old admitted with a primary admission diagnosis of ‘pneumonia’ to the Da Nang Hospital for Women and Children over 1 year. Results Of 2911 children hospitalised with pneumonia, 2735 (94.0%) were classified as ‘non-severe’ pneumonia by the admitting physician. In total, 2853 (98.0%) children received antibiotics. Intravenous antibiotics were given to 336 (12.3%) children with ‘non-severe’ and 157/176 (89.2%) children with ‘severe’ pneumonia; those with ‘non-severe’ pneumonia accounted for 68.2% (336/493) of intravenous antibiotics given. Only 19.3% (95/493) of children on intravenous antibiotics were stepped down to an oral antibiotic. Cefuroxime was the preferred oral agent, and ceftriaxone was the preferred injectable agent. Hospital admission for oral antibiotics in ‘non-severe’ pneumonia was a major cost driver, with an average direct cost of US$78.9 per patient, accounting for 54.0% of the total hospitalisation cost in the study cohort. In addition, 336 (12.3%) children with non-severe pneumonia received intravenous antibiotics without indication, accounting for a further 23.2% of hospitalisation costs. Conclusion Limiting unnecessary hospitalisation and considering early intravenous to oral step down antibiotic will reduce direct health system costs and morbidity in children with respiratory tract infections in Vietnam.
The influence of contextual factors on an individual’s ability to work with an assistance dog

Abstract Purpose First-time assistance dog handlers experience a profound life change when they bring an assistance dog into their home. Therefore, this article investigates the broad context of handlers’ lived experiences prior to and throughout the first year after acquiring an assistance dog. Materials and methods To understand holistic experiences better, semi-structured interviews were conducted with first-time assistance dog handlers (n = 7), parents (n = 7), assistance dog instructors (n = 6), carers/other individuals (n = 3) at four time points: before an individual received an assistance dog, and then at three further times for up to one year after they received the assistance dog. Results Inductive content analysis revealed that four main contextual factors (societal, social support, environmental and personal) influenced the lived experience of working with an assistance dog. Many of these factors were outside of the handler and the assistance dog organization’s control, and they were shown to cause many challenges for handlers. Conclusion These factors must, therefore, be taken into consideration when organizations make decisions about placing an assistance dog. IMPLICATIONS FOR REHABILITATION Societal influences can both hinder and facilitate the benefits first-time handlers receive with their assistance dog in public. Support from others is important to successfully integrate an assistance dog into a first-time handler’s life. A handler’s level of environmental control can influence their experiences with their assistance dog. Personal factors such as a handler’s experience of disability and motivation or resilience can impact experiences with their assistance dog.
Angiocrine FSTL1 (Follistatin-Like Protein 1) Insufficiency Leads to Atrial and Venous Wall Fibrosis via SMAD3 Activation

Supplemental Digital Content is available in the text. Objective: Angiocrine factors, mediating the endothelial-mural cell interaction in vascular wall construction as well as maintenance, are incompletely characterized. This study aims to investigate the role of endothelial cell–derived FSTL1 (follistatin-like protein 1) in vascular homeostasis. Approach and Results: Using conditional knockout mouse models, we show that loss of FSTL1 in endothelial cells (Fstl1ECKO) led to an increase of pulmonary vascular resistance, resulting in the heart regurgitation especially with tricuspid valves. However, this abnormality was not detected in mutant mice with Fstl1 knockout in smooth muscle cells or hematopoietic cells. We further showed that there was excessive αSMA (α-smooth muscle actin) associated with atrial endocardia, heart valves, veins, and microvessels after the endothelial FSTL1 deletion. There was also an increase in collagen deposition, as demonstrated in livers of Fstl1ECKO mutants. The SMAD3 (mothers against decapentaplegic homolog 3) phosphorylation (pSMAD3) was significantly enhanced, and pSMAD3 staining was colocalized with αSMA in vein walls, suggesting the activation of TGFβ (transforming growth factor β) signaling in vascular mural cells of Fstl1ECKO mice. Consistently, treatment with a TGFβ pathway inhibitor reduced the abnormal association of αSMA with the atria and blood vessels in Fstl1ECKO mutant mice. Conclusions: The findings imply that endothelial FSTL1 is critical for the homeostasis of vascular walls, and its insufficiency may favor cardiovascular fibrosis leading to heart failure.
EMT Transcription Factors Are Involved in the Altered Cell Adhesion under Simulated Microgravity Effect or Overloading by Regulation of E-cadherin

In order to study the effect of stress changes on cell adhesion, HUVEC, and MCF-7 cells were treated with simulated microgravity effect (SMG) and overloading (OL). Methods: Rotating Wall Vessel (2D-RWVS) bioreactor was used to create different culture conditions. In addition, the alteration of cell adhesion states, adhesion proteins, and relating factors of adhesion molecules under these two conditions were detected using cell adhesion assay, immunofluorescence, western blot, and qRT-PCR technology. Results: The results showed that the adhesion of cells decreased under SMG, while increased under OL. The expressions of integrin β1, paxillin, and E-cadherin under SMG condition were down-regulated as compared to that of the control group showing a time-dependent pattern of the decreasing. However, under OL condition, the expressions of adhesion proteins were up-regulated as compared to that of the control group, with a time-dependent pattern of increasing. EMT transcription factors Snail, twist, and ZEB1 were up-regulated under SMG while down-regulated under OL. Conclusion: Collectively our results indicated that cells could respond to stress changes to regulate the expressions of adhesion proteins and adapt their adhesion state to the altered mechanical environment. The altered cell adhesion in response to the mechanical stress may involve the changed expression of EMT-inducing factors, Snail, Twist, and ZEB1under the SMG/OL conditions.
Structural Changes and Astrocyte Response of the Lateral Geniculate Nucleus in a Ferret Model of Ocular Hypertension

We investigated structural changes and astrocyte responses of the lateral geniculate nucleus (LGN) in a ferret model of ocular hypertension (OH). In 10 ferrets, OH was induced via the injection of cultured conjunctival cells into the anterior chamber of the right eye; six normal ferrets were used as controls. Anterograde axonal tracing with cholera toxin B revealed that atrophic damage was evident in the LGN layers receiving projections from OH eyes. Immunohistochemical analysis with antibodies against NeuN, glial fibrillary acidic protein (GFAP), and Iba-1 was performed to specifically label neurons, astrocytes, and microglia in the LGN. Significantly decreased NeuN immunoreactivity and increased GFAP and Iba-1 immunoreactivities were observed in the LGN layers receiving projections from OH eyes. Interestingly, the changes in the immunoreactivities were significantly different among the LGN layers. The C layers showed more severe damage than the A and A1 layers. Secondary degenerative changes in the LGN were also observed, including neuronal damage and astrocyte reactions in each LGN layer. These results suggest that our ferret model of OH is valuable for investigating damages during the retina–brain transmission of the visual pathway in glaucoma. The vulnerability of the C layers was revealed for the first time.
eXnet: An Efficient Approach for Emotion Recognition in the Wild

Facial expression recognition has been well studied for its great importance in the areas of human–computer interaction and social sciences. With the evolution of deep learning, there have been significant advances in this area that also surpass human-level accuracy. Although these methods have achieved good accuracy, they are still suffering from two constraints (high computational power and memory), which are incredibly critical for small hardware-constrained devices. To alleviate this issue, we propose a new Convolutional Neural Network (CNN) architecture eXnet (Expression Net) based on parallel feature extraction which surpasses current methods in accuracy and contains a much smaller number of parameters (eXnet: 4.57 million, VGG19: 14.72 million), making it more efficient and lightweight for real-time systems. Several modern data augmentation techniques are applied for generalization of eXnet; these techniques improve the accuracy of the network by overcoming the problem of overfitting while containing the same size. We provide an extensive evaluation of our network against key methods on Facial Expression Recognition 2013 (FER-2013), Extended Cohn-Kanade Dataset (CK+), and Real-world Affective Faces Database (RAF-DB) benchmark datasets. We also perform ablation evaluation to show the importance of different components of our architecture. To evaluate the efficiency of eXnet on embedded systems, we deploy it on Raspberry Pi 4B. All these evaluations show the superiority of eXnet for emotion recognition in the wild in terms of accuracy, the number of parameters, and size on disk.
MOS Capacitance Measurements for PEALD TiO2 Dielectric Films Grown under Different Conditions and the Impact of Al2O3 Partial-Monolayer Insertion

In this paper, we report the plasma-enhanced atomic layer deposition (PEALD) of TiO2 and TiO2/Al2O3 nanolaminate films on p-Si(100) to fabricate metal-oxide-semiconductor (MOS) capacitors. In the PEALD process, we used titanium tetraisopropoxide (TTIP) as a titanium precursor, trimethyl aluminum (TMA) as an aluminum precursor and O2 plasma as an oxidant, keeping the process temperature at 250 °C. The effects of PEALD process parameters, such as RF power, substrate exposure mode (direct or remote plasma exposure) and Al2O3 partial-monolayer insertion (generating a nanolaminate structure) on the physical and chemical properties of the TiO2 films were investigated by Rutherford backscattering spectroscopy (RBS), Raman spectroscopy, grazing incidence X-ray diffraction (GIXRD), and field emission scanning electron microscopy (FESEM) techniques. The MOS capacitor structures were fabricated by evaporation of Al gates through mechanical mask on PEALD TiO2 thin film, followed by evaporation of an Al layer on the back side of the Si substrate. The capacitors were characterized by current density-voltage (J-V), capacitance-voltage (C-V) and conductance-voltage (G-V) measurements. Our results indicate that RF power and exposure mode promoted significant modifications on the characteristics of the PEALD TiO2 films, while the insertion of Al2O3 partial monolayers allows the synthesis of TiO2/Al2O3 nanolaminate with well-spaced crystalline TiO2 grains in an amorphous structure. The electrical characterization of the MOS structures evidenced a significant leakage current in the accumulation region in the PEALD TiO2 films, which could be reduced by the addition of partial-monolayers of Al2O3 in the bulk of TiO2 films or by reducing RF power.
PTPN23 binds the dynein adaptor BICD1 and is required for endocytic sorting of neurotrophin receptors

ABSTRACT Signalling by target-derived neurotrophins is essential for the correct development of the nervous system and its maintenance throughout life. Several aspects concerning the lifecycle of neurotrophins and their receptors have been characterised over the years, including the formation, endocytosis and trafficking of signalling-competent ligand–receptor complexes. However, the molecular mechanisms directing the sorting of activated neurotrophin receptors are still elusive. Previously, our laboratory identified Bicaudal-D1 (BICD1), a dynein motor adaptor, as a key factor for lysosomal degradation of brain-derived neurotrophic factor (BDNF)-activated TrkB (also known as NTRK2) and p75NTR (also known as NGFR) in motor neurons. Here, using a proteomics approach, we identified protein tyrosine phosphatase, non-receptor type 23 (PTPN23), a member of the endosomal sorting complexes required for transport (ESCRT) machinery, in the BICD1 interactome. Molecular mapping revealed that PTPN23 is not a canonical BICD1 cargo; instead, PTPN23 binds the N-terminus of BICD1, which is also essential for the recruitment of cytoplasmic dynein. In line with the BICD1-knockdown phenotype, loss of PTPN23 leads to increased accumulation of BDNF-activated p75NTR and TrkB in swollen vacuole-like compartments, suggesting that neuronal PTPN23 is a novel regulator of the endocytic sorting of neurotrophin receptors. Highlighted Article: PTPN23 associates with BICD1 via its dynein-binding region, and its loss results in accumulation of neurotrophin receptors in enlarged, ubiquitylated sorting compartments.
A regularized estimation approach for case‐cohort periodic follow‐up studies with an application to HIV vaccine trials

This paper discusses regression analysis of the failure time data arising from case‐cohort periodic follow‐up studies, and one feature of such data, which makes their analysis much more difficult, is that they are usually interval‐censored rather than right‐censored. Although some methods have been developed for general failure time data, there does not seem to exist an established procedure for the situation considered here. To address the problem, we present a semiparametric regularized procedure and develop a simple algorithm for the implementation of the proposed method. In addition, unlike some existing procedures for similar situations, the proposed procedure is shown to have the oracle property, and an extensive simulation is conducted and it suggests that the presented approach seems to work well for practical situations. The method is applied to an HIV vaccine trial that motivated this study.
Investigating E. coli coculture for resveratrol production with 13C metabolic flux analysis.

Resveratrol, a phytoalexin produced by plants, has several beneficial effects in humans. It can be produced using E. coli by introducing only three heterologous genes: TAL, 4CL, and STS. However, the resveratrol synthesis pathway requires two precursors, tyrosine and acetyl-CoA, which are produced by two branched central metabolic pathways. Therefore, overexpression of these genes in E. coli results in the production of only trace amounts of resveratrol. In this study, we attempted to produce resveratrol via coculture of two engineered strains in which the two metabolic pathways are activated. The first strain was engineered to produce p-coumaric acid using tyrosine as a precursor, which can be synthesized by the pentose phosphate pathway. The second strain produced resveratrol by combining p-coumaric acid from the first strain and malonyl-CoA synthesized from acetyl-CoA, which is produced by the glycolytic pathway. In total, 55.69 mg/L of resveratrol was produced from 20 g/L of glucose via coculture of these two strains in glucose minimal medium without any supplements. The metabolic fluxes in each of the strains producing resveratrol were successfully investigated by 13C metabolic flux analysis. The results showed that the balance between the citric acid cycle and malonyl-CoA supply node was important for resveratrol production.
Exposure to Digital Alcohol Marketing and Alcohol Use: A Systematic Review

Objective: Alcohol marketing has proliferated on digital media, such as websites, social media, and apps. A systematic review was conducted to examine studies of associations between exposure to digital alcohol marketing and alcohol consumption. Method: Eight electronic databases were searched for “alcohol” and “marketing” through 14 February 2017. Studies were included if exposure to digital alcohol marketing and alcohol consumption, or related attitudes and intentions, were assessed. Studies were excluded if they only measured exposure to alcohol depictions posted online by family and friends. Study quality was also assessed. Results: In all, 25 studies were included, including 2 randomized controlled trials, 15 cross-sectional studies, and 8 prospective cohort studies. There was a consistent finding across studies that participation and engagement with digital alcohol marketing—such as clicking on an alcohol ad, visiting an alcohol-branded website, liking or sharing an ad on social media, or downloading alcohol-branded content—was positively associated with alcohol use. The effects of simple exposure to digital alcohol advertising were inconclusive. Proper blinding of subjects, measuring exposures before the outcomes, and measuring the exposures multiple times would improve study quality. Conclusions: Although more research is needed, existing studies suggest that engagement with digital alcohol marketing is positively associated with increased alcohol consumption and increased binge or hazardous drinking behavior. Governments should consider implementing digital alcohol marketing regulations under the precautionary principle as the alcohol industry’s self-regulated marketing codes are likely ineffective at protecting populations vulnerable to alcohol-related harm.
Comparison of endoscopic naso-gallbladder drainage and percutaneous transhepatic gallbladder drainage in acute suppurative cholecystitis

Abstract Introduction: Transitional drainage, which is followed by cholecystectomy plays a key role in the management of acute cholecystitis, especially in high-risk surgical patients. Endoscopic naso-gallbladder drainage (ENGBD) is an alternative to percutaneous transhepatic gallbladder drainage (PTGBD) for patients who need temporary drainage. There is a lack of prospective comparison on the relevant outcomes of the two drainage methods during the period of drainage, especially the subsequent cholecystectomy. Methods: This is a randomized controlled two-arm non-blind single center trial. Patients with acute cholecystitis undergo emergent or early cholecystectomy and need drainage will be randomly assigned to group PTGBD or ENGBD. Pain score is defined as the primary endpoint, whereas several secondary endpoints, such as the rates of technical success, clinical remission, open conversion of cholecystectomy will be determined to elucidate more detailed differences between two groups. The general feasibility, safety, and quality checks required for high-quality evidence will be adhered to. Discussion: This study would provide the first type A evidence concerning the comparison of ENGBD versus PTGBD in surgically high-risk patients with acute cholecystitis, it will be the first trial designed to determine the impact of two drainage methods on not only peri-drainage but also peri-LC. Trial registration: NCT03701464. Registered on October 10, 2018.