Miracle-dz/UniFAR-FTUs huggingface dataset:
Curcumin attenuates hypoxia/reoxygenation-induced myocardial injury

Curcumin (Cur) has been reported to function as an antioxidant and anti-inflammatory agent and to play a role in anti-atherosclerosis. The present study aimed to explore the protective effect of Cur on hypoxia/reoxygenation (H/R) injury. The morphological changes in H9c2 cardiomyocytes were observed under an inverted microscope. Cell viability was determined by Cell Counting Kit-8 (CCK-8). Lactate dehydrogenase (LDH) level, malondialdehyde (MDA) level and the antioxidant superoxide dismutase (SOD) activity were determined by corresponding kits. Apoptosis and reactive oxygen species (ROS) levels were determined by flow cytometry. Endoplasmic reticulum (ER) stress-related factors, which were examined by quantitative real-time polymerase chain reaction (qPCR) and western blot analysis, included 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP). Extracellular signal regulating kinase 1/2 (ERK1/2), p38, c-Jun NH2-terminal kinase (JNK) and the phosphorylation levels of key proteins in the mitogen-activated protein kinase (MAPK) signaling pathway were all determined by western blot analysis. Compared to the control group, the cell morphology of the H9c2 cells was obviously altered upon H/R. Cell viability was significantly decreased, while apoptosis was significantly increased by H/R. We also observed that the levels of LDH and MDA were elevated and the activity of SOD was decreased in the H/R group. Notably, LDH, MDA and SOD levels were reversed following treatment with Cur; while apoptosis and ROS levels in the H/R injury group were decreased by Cur. H/R injury-triggered ER stress and the MAPK signaling pathway were suppressed by Cur. These results demonstrated that Cur has a protective effect on cardiomyocytes via suppression of ER stress and the MAPK pathway.
Intracerebroventricular Infusion of Gangliosides Augments the Adult Neural Stem Cell Pool in Mouse Brain

We previously reported that ganglioside GD3 is the predominant species in neural stem cells (NSCs) and reduced postnatal NSC pools are observed in both the subventricular zone and dentate gyrus (DG) of GD3-synthase knockout (GD3S-KO) mouse brains. Specifically, deficiency of GD3 in GD3S-KO animals revealed a dramatic reduction in cellularity in the DG of the hippocampus of the developing mouse brain, resulting in severe behavioral deficits in these animals. To further evaluate the functional role of GD3 in postnatal brain, we performed rescue experiments by intracerebroventricular infusion of ganglioside GD3 in adult GD3S-KO animals and found that it could restore the NSC pools and enhance the NSCs for self-renewal. Furthermore, 5xFAD mouse model was utilized, and GD3 restored NSC numbers and GM1 promoted neuronal differentiation. Our results thus demonstrate that exogenously administered gangliosides are capable to restore the function of postnatal NSCs. Since ganglioside expression profiles are associated not only with normal brain development but also with pathogenic mechanisms of diseases, such as Alzheimer’s disease, we anticipate that the administration of exogenous gangliosides, such as GD3 and GM1, may represent a novel and effective strategy for promoting adult neurogenesis in damaged brain for disease treatment.
Histoplasmosis progresiva diseminada en un paciente sin VIH

Objetivo: reportar un caso de histoplasmosis progresiva diseminada en un paciente sin inmunodeficiencia, con Elisa para VIH negativo y discusion con respecto a la presentacion clinica y diagnostico. Diseno del estudio: reporte de un caso clinico y revision de la literatura. Metodos: historia clinica, histopatologia, reporte de paraclinicos, revision de articulos publicados en revistas indexadas. Resultados: el paciente presenta sintomas de 1 mes de duracion con perdida de peso, hemoptisis, disfagia progresiva, lesiones en piel y mucosas ulceradas. En las biopsias tomadas se identificaron blastoconidias intracelulares y levaduras en los tejidos de ganglio, mucosa gastrica y medula osea. Conclusiones: es un caso de histoplamasmosis progresiva en paciente sin VIH con compromiso pulmonar, gastrico y tejido linfatico.
Prevalence, Contribution to Disease Burden and Management of Comorbid Depression and Anxiety in Chronic Obstructive Pulmonary Disease: A Narrative Review

Abstract Mental health issues such as depression and anxiety are common comorbidities of individuals suffering from chronic obstructive pulmonary disease (COPD), though they are frequently underdiagnosed and consequently undertreated. To that end we sought to identify the impact of co-morbid anxiety and depression in COPD patients and evaluate recent evidence regarding the management of such cases. A Pubmed search was conducted for relevant original articles with emphasis on the past 5 years. The studies we identified indicate that psychiatric comorbidity negatively impacts the prognosis of COPD, as it is associated with reduced adherence to treatment, reduced physical activity and a general reduction in quality of life, in turn leading to more frequent exacerbations and increased severity of exacerbations (which are more likely to require hospitalization), resulting in increased mortality. Despite the evidence showing a high prevalence and exceedingly negative impact of depression and anxiety in patients with COPD, very few clinical trials (for both pharmacological and psychological treatments) with small sample sizes have been conducted in this population. As treatment for co-morbid mental health conditions may reduce mortality, interventions to ensure prompt identification of mental health issues and subsequent initiation of treatment are warranted.
Novel Pituitary Actions of Epidermal Growth Factor: Receptor Specificity and Signal Transduction for UTS1, EGR1, and MMP13 Regulation by EGF

Epidermal growth factor (EGF) is a member of the EGF-like ligands family, which plays a vital role in cell proliferation, differentiation, and folliculogenesis through binding with EGF receptors, including ErbB1 (EGFR/HER1), ErbB2 (HER2), ErbB3 (HER3), and ErbB4 (HER4). In mammals, many functional roles of EGF have been reported in the ovaries and breasts. However, little is known about the functions of EGF in the pituitary, especially in teleost. In this study, using grass carp pituitary cells as the model, we try to examine the direct pituitary actions of EGF in teleost. Firstly, transcriptomic analysis showed that 599 different expressed genes (DEGs) between the control and EGF-treatment group were mainly involved in cell proliferation, cell migration, signal transduction, and transcriptional regulation. Then, we further confirmed that EGF could significantly induce UTS1, EGR1, and MMP13 mRNA expression in a time-and dose-dependent manner. The stimulatory actions of EGF on UTS1 and EGR1 mRNA expression were mediated by the MEK1/2/ERK1/2 and PI3K/AKT/mTOR pathways coupled with both ErbB1 and ErbB2 in grass carp pituitary cells. The receptor specificity and signal transductions for the corresponding responses on MMP13 mRNA expression were also similar, except that the ErbB2 and PI3K/AKT/mTOR pathway were not involved. As we know, MMP13 could release EGF from HB-EGF. Interestingly, our data also showed that the MMPs inhibitor BB94 could suppress EGF-induced UTS1 and EGR1 mRNA expression. These results, taken together, suggest that the stimulatory actions of EGF on UTS1 and EGR1 mRNA expression could be enhanced by EGF-induced MMP13 expression in the pituitary.
Piezotronic Effect Modulated Flexible AlGaN/GaN High-Electron-Mobility Transistors.

Flexible electronic technology has attracted great attentions due to its wide range of potential applications in the fields of healthcare, robotics and artificial intelligence, etc. In this letter, we have successfully fabricated flexible AlGaN/GaN High-Electron-Mobility Transistors (HEMTs) arrays through a low damage and wafer-scale substrate transfer technology from a rigid Si substrate. The flexible AlGaN/GaN HEMTs have excellent electrical performances with the Id,max achieving 290 mA/mm at Vgs = +2 V and the gm,max reaching to 40 mS/mm. The piezotronic effect provides a new freedom to optimize device performances, and flexible HEMTs can endure larger mechanical distortions. Based on the piezotronic effect, we applied an external stress to significantly modulate the electrical performances of the flexible HEMTs. The piezotronic effect modulated flexible AlGaN/GaN HEMTs exhibit great potentials in human-machine interface, intelligent micro-inductor system, and active sensors, etc, and open a new window to sensing or feedback external mechanical stimuli and so on.
A Resource-Optimized VLSI Implementation of a Patient-Specific Seizure Detection Algorithm on a Custom-Made 2.2 cm$^2$ Wireless Device for Ambulatory Epilepsy Diagnostics

A patient-specific epilepsy diagnostic solution in the form of a wireless wearable ambulatory device is presented. First, the design, VLSI implementation, and experimental validation of a resource-optimized machine learning algorithm for epilepsy seizure detection are described. Next, the development of a mini-PCB that integrates a low-power wireless data transceiver and a programmable processor for hosting the seizure detection algorithm is discussed. The algorithm uses only EEG signals from the frontal lobe electrodes while yielding a seizure detection sensitivity and specificity competitive to the standard full EEG systems. The experimental validation of the algorithm VLSI implementation proves the possibility of conducting accurate seizure detection using quickly-mountable dry-electrode headsets without the need for uncomfortable/painful through-hair electrodes or adhesive gels. Details of design and optimization of the algorithm, the VLSI implementation, and the mini-PCB development are presented and resource optimization techniques are discussed. The optimized implementation is uploaded on a low-power Microsemi Igloo FPGA, requires 1237 logic elements, consumes 110 $\mu$W dynamic power, and yields a minimum detection latency of 10.2 $\mu$s. The measurement results from the FPGA implementation on data from 23 patients (198 seizures in total) shows a seizure detection sensitivity and specificity of 92.5% and 80.1%, respectively. Comparison to the state of the art is presented from system integration, the VLSI implementation, and the wireless communication perspectives.
Perspectives of Clinicians, Staff, and Veterans in Transitioning Veterans from non-VA Hospitals to Primary Care in a Single VA Healthcare System.

BACKGROUND Veterans with healthcare needs utilize both Veterans Health Administration (VA) and non-VA hospitals. These dual-use veterans are at high risk of adverse outcomes due to the lack of coordination for safe transitions. OBJECTIVES The aim of this study was to understand the barriers and facilitators to providing high-quality continuum of care for veterans transitioning from non-VA hospitals to the VA primary care setting. DESIGN Guided by the practical robust implementation and sustainability model (PRISM) and the ideal transitions of care, we conducted a qualitative assessment using semi-structured interviews with clinicians, staff, and patients. SETTING This study was conducted at a single urban VA medical center and two non-VA hospitals. PARTICIPANTS A total of 70 participants, including 52 clinicians and staff (23 VA and 29 non-VA) involved in patient transition and 18 veterans recently discharged from non-VA hospitals, were included in this study. APPROACH Data were analyzed using a conventional content analysis and managed in Atlas.ti (Berlin, Germany). RESULTS Four major themes emerged where participants consistently discussed that transitions were delayed when they were not able to (1) identify patients as veterans and notify VA primary care of discharge, (2) transfer non-VA hospital medical records to VA primary care, (3) obtain follow-up care appointments with VA primary care, and (4) write VA formulary medications for veterans that they could fill at VA pharmacies. Participants also discussed factors involved in smooth transition and recommendations to improve care coordination. CONCLUSIONS All participants perceived the current transition-of-care process across healthcare systems to be inefficient. Efforts to improve quality and safety in transitional care should address the challenges clinicians and patients experience when transitioning from non-VA hospitals to VA primary care.
Immune checkpoint inhibitors in people living with HIV: what about anti-HIV effects?

: Immune checkpoint inhibitors (ICPi) have shown major therapeutic successes when used in various cancers. In the HIV field a double benefit of such ICPi should result from their dual ability to restore in-vitro HIV-specific CD8 T-cell functions and to enhance HIV production from reservoir cells, thus fulfilling the goals of the 'shock and kill' concept proposed as an HIV cure therapeutic strategy.We conducted a systematic review to identify studies reporting the tolerance profile of ICPi and their effects on HIV plasma loads (pVL), CD4 count, HIV reservoirs (cell-associated HIV-DNA) and/or HIV-specific CD8 T in PLWH.Thirty-four articles were included for a total 176 participants. 12.1% participants experienced severe adverse events and 49.4% nonsevere adverse events. pVL remained stable in 91.9% participant, showed increases in 5.8% participant, and decreases in 2.3%. CD4 count remained stable in 60.7% participants, showed increases in 24.6%, and decreases in 14.7%. Regarding ICPi effects on HIV-DNA and HIV-specific immunity, we identified three distinct profiles: profile I, transient pVL increases followed by a boost in HIV-specific CD8 T cells concomitant to a decrease in HIV-DNA, reported in one participant. Profile II: increase in HIV-specific CD8 T cells without changes in pVL or HIV-DNA, reported in three participants. III: no effect, reported in five participants.In conclusion, the clinical, virological and immunological safety profiles of ICPi reported in about 200 PLWH appear to be favorable but their still modest results in terms of HIV cure strategy.
Commentary: Targeting herpetic keratitis by immunomodulation of IL-27 signaling

30. de Aquino MT, Kapil P, Hinton DR, Phares TW, Puntambekar SS, Savarin C, et al. IL‐27 limits central nervous system viral clearance by promoting IL‐10 and enhances demyelination. J Immunol 2014;193:285‐94. 31. de Almeida Nagata DE, Demoor T, Ptaschinski C, Ting HA, Jang S, Reed M, et al. IL‐27R‐mediated regulation of IL‐17 controls the development of respiratory syncytial virus‐associated pathogenesis. Am J Pathol 2014;184:1807‐18.
Prediction of Functional Impairment from Patient Evaluations of Multiple Sclerosis Symptoms and Symptom Change

This paper reports the results of a survey using an inexpensive self-report instrument to assess patient evaluations of severity of symptoms among those with multiple sclerosis (MS). A mail survey of New York City MS chapter members resulted in collection of 747 questionnaires to gather information on self-assessed symptom severity, functional impairment, and demographic characteristics of the respondents. Data focusing on patients' perceptions of variation in symptom severity over time and the relationship between patient-assessed symptom severity and functional impairment are presented. Patient perceptions mirrored the clinical picture: MS symptoms were reported to increase in severity over time for the majority of patients. Perceived symptom severity accounted for about one-half of the variation in functional impairment, an indication that other factors in addition to the physical impairment itself are related to how disabled the MS patient becomes.
Assessment of in vitro Effects of Anthocyanins on Platelet Function.

Background Increased platelet activity plays a significant role in the development of arterial thrombosis and cardiovascular disease (CVD). Natural antioxidants including anthocyanin (AC) have gained considerable interest due to their hypothesized antithrombotic potential. Primary Study Objective Our study aimed to examine the in vitro effect of AC compounds on platelet activation and aggregation. Methods Fasting blood samples were collected from healthy volunteers (n = 13). A full blood examination was done to exclude any abnormal specimen. Flow cytometer assessed platelet activity by recording platelet surface markers expression of P-selectin (CD62P) and PAC-1. Platelet aggregation studies were performed by stimulating platelets using three different agonists adenosine diphosphate (ADP), collagen and arachidonic acid (AA). Setting The study was done in the school of Medical Sciences, Griffith University. Participants Thirteen healthy adult participants were involved for blood collection. Intervention AC was prepared using hemicellulose capsules sourced from Bilberries and Black Currants. Results Anthocyanin (50 mg/L) significantly inhibited AA-induced platelet aggregation. Expression of P-selectin was significantly suppressed by 50 mg/L AC as measured by flow cytometer. Conclusions AC attenuates platelet function by suppressing P-selectin expression and influencing Thromboxane A2 pathway (AA stimulation). These results provide further evidence for the effect of AC and the possible mechanism by which AC reduces platelet aggregation and activation. This study supports future human intervention trials to show that AC may act as a complement to other antiplatelet agents in reducing the risk of thrombosis.
Assessment of biochemical recurrence of prostate cancer (Review)

The assessment of the risk of biochemical recurrence (BCR) is critical in the management of males with prostate cancer (PC). Over the past decades, a comprehensive effort has been focusing on improving risk stratification; a variety of models have been constructed using PC-associated pathological features and molecular alterations occurring at the genome, protein and RNA level. Alterations in RNA expression (lncRNA, miRNA and mRNA) constitute the largest proportion of the biomarkers of BCR. In this article, we systemically review RNA-based BCR biomarkers reported in PubMed according to the PRISMA guidelines. Individual miRNAs, mRNAs, lncRNAs and multi-gene panels, including the commercially available signatures, Oncotype DX and Prolaris, will be discussed; details related to cohort size, hazard ratio and 95% confidence intervals will be provided. Mechanistically, these individual biomarkers affect multiple pathways critical to tumorigenesis and progression, including epithelial-mesenchymal transition (EMT), phosphatase and tensin homolog (PTEN), Wnt, growth factor receptor, cell proliferation, immune checkpoints and others. This variety in the mechanisms involved not only validates their associations with BCR, but also highlights the need for the coverage of multiple pathways in order to effectively stratify the risk of BCR. Updates of novel biomarkers and their mechanistic insights are considered, which suggests new avenues to pursue in the prediction of BCR. Additionally, the management of patients with BCR and the potential utility of the stratification of the risk of BCR in salvage treatment decision making for these patients are briefly covered. Limitations will also be discussed.
Dame Sheila Patricia Violet Sherlock. 31 March 1918 – 30 December 2001 Elected FRS 2001

Dame Sheila Patricia Violet Beckett Sherlock was the world's leading female physicianscientist of the twentieth century. Her brilliant, wide-ranging, original contributions to the investigation, diagnosis, classification, epidemiology, pathogenesis and management of liver disease played a leading role in the establishment of hepatology as a medical specialty. Her rigorous, highly focused, studies combined experimental and laboratory investigations with meticulous clinical observation, encompassed most aspects of liver function, disease and treatment, and led directly to enormous benefit for millions of patients. Her remarkable individual personality also had a profound influence not only on her medical and scientific specialty but also on several generations of physicians throughout the world. She was the first female professor of medicine and head of a department of medicine in the UK, and the pioneer of women in modern medicine. The importance of her contributions to knowledge and her massive influence on training in and the practice of medicine related to liver disease were recognized by a glittering array of honours and awards from professional societies and academic institutions throughout the world, including 19 honorary degrees, and, very belatedly, election to Fellowship of The Royal Society in the last year of her life.
Transcriptional Regulator TonEBP Mediates Oxidative Damages in Ischemic Kidney Injury

TonEBP (tonicity-responsive enhancer binding protein) is a transcriptional regulator whose expression is elevated in response to various forms of stress including hyperglycemia, inflammation, and hypoxia. Here we investigated the role of TonEBP in acute kidney injury (AKI) using a line of TonEBP haplo-deficient mice subjected to bilateral renal ischemia followed by reperfusion (I/R). In the TonEBP haplo-deficient animals, induction of TonEBP, oxidative stress, inflammation, cell death, and functional injury in the kidney in response to I/R were all reduced. Analyses of renal transcriptome revealed that genes in several cellular pathways including peroxisome and mitochondrial inner membrane were suppressed in response to I/R, and the suppression was relieved in the TonEBP deficiency. Production of reactive oxygen species (ROS) and the cellular injury was reproduced in a renal epithelial cell line in response to hypoxia, ATP depletion, or hydrogen peroxide. The knockdown of TonEBP reduced ROS production and cellular injury in correlation with increased expression of the suppressed genes. The cellular injury was also blocked by inhibitors of necrosis. These results demonstrate that ischemic insult suppresses many genes involved in cellular metabolism leading to local oxidative stress by way of TonEBP induction. Thus, TonEBP is a promising target to prevent AKI.
The Effect of a High Amount of Micro-Fillers on the Long-Term Properties of Concrete

Concretes in which a large portion of fine natural aggregate is replaced with inert mineral powders would offer both economic and ecological benefits for the concrete industry, and they represent eco-friendly materials. Moreover, using the powders having potential pozzolanic effect could have positive extra effect on the properties of concrete. This paper analyses the impact of a high dosage of three kinds of micro-fillers (brick, concrete and glass powders) on the properties of concrete over a three-year period. Microfillers were applied as 40% replacement of 0/4 aggregate by volume. Samples having high dosage of micro-fillers and thus a higher binder volume achieved excellent values of both compressive (from 31 to 48 MPa in 28 days, and from 67 to 93 MPa in three years) and flexural strength (from 6.3 to 8.4 MPa in 28 days, and from 7.1 to 11.1 MPa in three years). Both samples with brick powder and concrete powder achieved the biggest strength values; however, due to better performance in durability parameters (capillary water absorption coefficient and density), sample prepared with glass powder can be identified as having the biggest potential for intended use.