Miracle-dz/UniFAR-FTUs huggingface dataset:
Rosmarinic Acid, the Main Effective Constituent of Orthosiphon stamineus, Inhibits Intestinal Epithelial Apoptosis Via Regulation of the Nrf2 Pathway in Mice

Many studies have shown that Orthosiphon stamineus extract (OE) has antioxidant activity, and we previously reported that OE protects the intestine against injury from a high-fat diet. However, the molecular mechanism underlying this protective effect of OE was unclear. Here, OE was separated according to polarity and molecular weight, and the antioxidant activity of each component was compared. The components with the highest antioxidant activity were analyzed by HPLC, which confirmed that rosmarinic acid (RA) was the main effective constituent in OE. OE and RA were then tested in a mouse high-fat diet-induced intestinal injury model. The antioxidant indices and morphological characteristics of the mouse jejunum were measured, and activation of the nuclear factor E2-related factor 2 (Nrf2) pathway and apoptosis of jejunal epithelial cells were analyzed. Of all the constituents in OE, RA contributed the most. Both RA and OE activated the Nrf2 pathway and increased downstream antioxidant enzyme activity. RA and OE protected the mouse intestine against high-fat diet-induced oxidative stress by preventing intestinal epithelial cell apoptosis via both extracellular and intracellular pathways. Thus, RA, the main effective constituent in OE, inhibits intestinal epithelial apoptosis by regulating the Nrf2 pathway in mice.
LENGTH CHANGE OF THE ILIOFEMORAL LIGAMENT DURING TESTS FOR ANTERIOR MICROINSTABILITY OF THE HIP JOINT: A CADAVERIC VALIDITY STUDY.

Purpose/Background There is little information to support the use of clinical tests to assess for microinstability of the hip joint. The purpose of this study was to use a string model to describe and compare length changes of the iliofemoral ligament in the test positions commonly used to assess hip ligament laxity. Methods Twelve hip joints from nine cadavers (4 male; 5 female) with lifespans of 57-84 years of age were studied. A string model representing the medial and lateral arms of the iliofemoral ligament was secured to the proximal and distal attachment points. The amount of length change of the string model was compared in four test positions: 1) external rotation, 2) hyperextension-external rotation 3) abduction-extension-external rotation, and 4) adduction--extension-external rotation. Results For the medial arm, the greatest change occurred in the adduction-extension-external rotation position (12.7mm). This was significantly greater than the external rotation (5.1mm; p=0.002) and abduction-extension-external rotation position (1.9mm; p<0.001). The lateral arm also had the greatest excursion in the adduction-extension-external rotation position (16.6mm). This length change was significantly greater than the external rotation position (8.6mm; p=0.002), the hyperextension-external rotation (11.1mm; p=0.047), and the abduction-extension-external rotation position (5.6mm; p<0.001). Conclusions Tests used for hip instability cause various levels of tension through the iliofemoral ligament. The combination of hip extension and external rotation increased the length change of string model and was maximized with hip adduction. The least amount of change occurred with the addition of hip abduction to extension and external rotation. Clinical Relevance Clinicians may use the information to help interpret tests for instability of the hip and may consider the combined position of hip extension, external rotation, and adduction to elucidate involvement of the iliofemoral femoral ligament. Level of Evidence 2b; Exploratory cohort study with good reference standards.
Design and Evaluation of a Patient Monitoring Dashboard for Emergency Departments

Identification of risk patients in emergency departments is a complex interplay between clinicians, patients, working procedures, and information systems. Through a mixed methods approach, we have developed an novel patient monitoring dashboard that couples clinical data streams to convey the state and trajectory of patients admitted to the emergency d epartment. In this paper, we describe the design and implementation of the novel system by providing a description of how the project was conceived, divided into subsequent phases, and is currently being executed. Experience from this work highlights the importance of carefully assessing each on-site installation point, interdisciplinary partnerships through embedded presence, and continuous emphasis on the purpose and aim as a mean to greatly improve project momentum and buy-in.
NifA is the master regulator of both nitrogenase systems in Rhodobacter capsulatus

Rhodobacter capsulatus fixes atmospheric nitrogen (N2) by a molybdenum (Mo)‐nitrogenase and a Mo‐free iron (Fe)‐nitrogenase, whose production is induced or repressed by Mo, respectively. At low nanomolar Mo concentrations, both isoenzymes are synthesized and contribute to nitrogen fixation. Here we examined the regulatory interplay of the central transcriptional activators NifA and AnfA by proteome profiling. As expected from earlier studies, synthesis of the structural proteins of Mo‐nitrogenase (NifHDK) and Fe‐nitrogenase (AnfHDGK) required NifA and AnfA, respectively, both of which depend on the alternative sigma factor RpoN to activate expression of their target genes. Unexpectedly, NifA was found to be essential for the synthesis of Fe‐nitrogenase, electron supply to both nitrogenases, biosynthesis of their cofactors, and production of RpoN. Apparently, RpoN is the only NifA‐dependent factor required for target gene activation by AnfA, since plasmid‐borne rpoN restored anfH transcription in a NifA‐deficient strain. However, plasmid‐borne rpoN did not restore Fe‐nitrogenase activity in this strain. Taken together, NifA requirement for synthesis and activity of both nitrogenases suggests that Fe‐nitrogenase functions as a complementary nitrogenase rather than an alternative isoenzyme in R. capsulatus.
Human Papillomavirus–Attributable Cancers — United States, 2012–2016

Human papillomavirus (HPV) causes nearly all cervical cancers and some cancers of the vagina, vulva, penis, anus, and oropharynx (1). * Most HPV infections are asymptomatic and clear spontaneously within 1 to 2 years; however, persistent infection with oncogenic HPV types can lead to development of precancer or cancer (2). In the United States, the 9-valent HPV vaccine (9vHPV) is available to protect against oncogenic HPV types 16, 18, 31, 33, 45, 52, and 58 as well as nononcogenic types 6 and 11 that cause genital warts. CDC analyzed data from the U.S. Cancer Statistics (USCS)† to assess the incidence of HPV-associated cancers and to estimate the annual number of cancers caused by HPV, overall and by state, during 2012-2016 (3,4). An average of 43,999 HPV-associated cancers were reported annually, and an estimated 34,800 (79%) of those cancers were attributable to HPV. Of these 34,800 cancers, an estimated 32,100 (92%) were attributable to the types targeted by 9vHPV, with 19,000 occurring among females and 13,100 among males. The most common were cervical (9,700) and oropharyngeal cancers (12,600). The number of cancers estimated to be attributable to the types targeted by 9vHPV ranged by state from 40 to 3,270 per year. HPV vaccination is an important strategy that could prevent these cancers, but during 2018, only half of adolescents were up to date on HPV vaccination (5). These surveillance data from population-based cancer registries can be used to inform the planning for, and monitor the long-term impact of, HPV vaccination and cancer screening efforts nationally and within states.
Over-Expression of CHD4 Is an Independent Biomarker of Poor Prognosis in Patients with Rectal Cancers Receiving Concurrent Chemoradiotherapy

Neoadjuvant concurrent chemoradiotherapy (CCRT), followed by radical proctectomy, is the standard treatment for locally advanced rectal cancer. However, a poor response and therapeutic resistance continue to occur despite this treatment. In this study, we analyzed the microarray datasets (GSE68204) of rectal cancer from the Gene Expression Omnibus database, and identified CHD4 as one of the most significantly up-regulated genes among all subunits of the nucleosome remodeling and histone deacetylation (NuRD) complex, in non-responders to CCRT, among locally advanced rectal cancer (LARC) patients. We confirmed the predictive and prognostic significance of CHD4 expression in CCRT treatment, and its correlation with other clinicopathological features, such as tumor regression grade (TRG), therapeutic response, and patient survival. This was carried out by immunohistochemical studies on endoscopic biopsy tissues from 172 rectal cancer patients, receiving neoadjuvant concurrent chemoradiotherapy (CCRT). A high expression of CHD4 was significantly associated with pre-treatment tumor status (p < 0.001) and lymph node metastasis (p < 0.001), post-treatment tumor status (p < 0.001), and lymph node metastasis (p < 0.001), vascular invasion (p = 0.042), and tumor regression grade (p = 0.001). A high expression of CHD4 could also predict poor disease-specific survival and metastasis-free survival (log-rank test, p = 0.0373 and p < 0.0001, respectively). In multivariate Cox proportional-hazards regression analysis, CHD4 overexpression was an independent factor of poor prognosis for metastasis-free survival (HR, 4.575; 95% CI, 1.717–12.192; p = 0.002). By in vitro studies, based on cell line models, we also demonstrated that, the overexpression of CHD4 induced radio-resistance in microsatellite instability-high (MSI-H) colorectal cells (CRCs). On the contrary, the knockdown of CHD4 enhanced radiosensitivity in microsatellite stable (MSS) CRCs. Altogether, we have identified CHD4 as an important regulator of radio-resistance in both MSI-H and MSS CRC cell lines.
Early Experience With Transcatheter Mitral Valve Replacement: A Systematic Review

Background Transcatheter mitral valve replacement (TMVR) has emerged as an alternative therapeutic option for the treatment of severe mitral regurgitation in patients with prohibitive or high surgical risk. The aim of this systematic review is to evaluate the clinical procedural characteristics and outcomes associated with the early TMVR experience. Methods and Results Published studies and international conference presentations reporting data on TMVR systems were identified. Only records including clinical characteristics, procedural results, and 30‐day and midterm outcomes were analyzed. A total of 16 publications describing 308 patients were analyzed. Most patients (65.9%) were men, with a mean age of 75 years (range: 69–81 years) and Society for Thoracic Surgery Predicted Risk of Mortality score of 7.7% (range: 6.1–8.6%). The etiology of mitral regurgitation was predominantly secondary or mixed (87.1%), and 81.5% of the patients were in New York Heart Association class III or IV. A transapical approach was used in 81.5% of patients, and overall technical success was high (91.7%). Postprocedural mean transmitral gradient was 3.5 mm Hg (range: 3–5.5 mm Hg), and only 4 cases (1.5%) presented residual moderate to severe mitral regurgitation. Procedural and all‐cause 30‐day mortality were 4.6% and 13.6%, respectively. Left ventricular outflow obstruction and conversion to open heart surgery were reported in 0.3% and 4% of patients, respectively. All‐cause and cardiovascular‐related mortality rates were 27.6% and 23.3%, respectively, after a mean follow‐up of 10 (range: 3 to 24) months. Conclusions TMVR was a feasible, less invasive alternative for treating severe mitral regurgitation in patients with high or prohibitive surgical risk. TMVR was associated with a high rate of successful valve implantation and excellent hemodynamic results. However, periprocedural complications and all‐cause mortality were relatively high.
Stem cell transplantation: A promising therapy for spinal cord injury.

Spinal cord injury (SCI) causes irreversible functional loss of the affected population. The incidence of SCI keeps increasing, resulting in huge burden on the society. The pathogenesis of SCI involves neuron death and exotic reaction, which could impede neuron regeneration. In clinic, the limited regenerative capacity of endogenous cells after SCI is a major problem. Recent studies have demonstrated that a variety of stem cells such as induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), mesenchymal stem cells (MSCs) and neural progenitor cells (NPCs) /neural stem cells (NSCs) have therapeutic potential for SCI. However, the efficacy and safety of these stem cell based therapy for SCI remain controversial. In this review, we introduce the pathogenesis of SCI, summarize current status of the application of these stem cells in SCI repair, and discuss possible mechanisms responsible for functional recovery of SCI after stem cell transplantation. Finally, we highlight several areas for further exploitation of stem cells as a promising regenerative therapy of SCI.
MHC Genomics and Disease: Looking Back to Go Forward

Ancestral haplotypes are conserved but extremely polymorphic kilobase sequences, which have been faithfully inherited over at least hundreds of generations in spite of migration and admixture. They carry susceptibility and resistance to diverse diseases, including deficiencies of CYP21 hydroxylase (47.1) and complement components (18.1), as well as numerous autoimmune diseases (8.1). The haplotypes are detected by segregation within ethnic groups rather than by SNPs and GWAS. Susceptibility to some other diseases is carried by specific alleles shared by multiple ancestral haplotypes, e.g., ankylosing spondylitis and narcolepsy. The difference between these two types of association may explain the disappointment with many GWAS. Here we propose a pathway for combining the two different approaches. SNP typing is most useful after the conserved ancestral haplotypes have been defined by other methods.
A pair of novel bisindole alkaloid enantiomers from marine fungus Fusarium sp. XBB-9

Abstract A preliminary research on the marine fungus Fusarium sp. XBB-9 resulted in a pair of novel bisindole alkaloid enantiomers, (+)- and (–)-fusaspoid A (1a/1b) and 12 diverse compounds. One strain many compound (OSMAC) method was used to enhance as many biosynthetic pathways as possible. The structures of the compounds were elucidated by spectroscopic analysis, and the absolute configuration of 1a was determined by X-ray single-crystal diffraction analysis. Compounds 1a and 1b were tested for cytotoxic activity against HCT-15, RKO cell lines, but were inactive. Compounds 1a and 1b were the first example of bisindole alkaloids isolated from fungus Fusarium sp. XBB-9.
17β-Estradiol nongenomically induces vascular endothelial H2S release by promoting phosphorylation of cystathionine γ-lyase

Estrogen exerts its cardiovascular protective role at least in part by regulating endothelial hydrogen sulfide (H2S) release, but the underlying mechanisms remain to be fully elucidated. Estrogen exerts genomic effects, i.e. those involving direct binding of the estrogen receptor (ER) to gene promoters in the nucleus, and nongenomic effects, mediated by interactions of the ER with other proteins. Here, using human umbilical vein endothelial cells (HUVECs), immunological detection, MS-based analyses, and cGMP and H2S assays, we show that 17β-estradiol (E2) rapidly enhances endothelial H2S release in a nongenomic manner. We found that E2 induces phosphorylation of cystathionine γ-lyase (CSE), the key enzyme in vascular endothelial H2S generation. Mechanistically, E2 enhanced the interaction of membrane ERα with the Gα subunit Gαi-2/3, which then transactivated particulate guanylate cyclase-A (pGC-A) to produce cGMP, thereby activating protein kinase G type I (PKG-I). We also found that PKG-Iβ, but not PKG-Iα, interacts with CSE, leading to its phosphorylation, and rapidly induces endothelial H2S release. Furthermore, we report that silencing of either CSE or pGC-A in mice attenuates E2-induced aorta vasodilation. These results provide detailed mechanistic insights into estrogen's nongenomic effects on vascular endothelial H2S release and advance our current understanding of the protective activities of estrogen in the cardiovascular system.
Best-Evidence for the Rehabilitation of Chronic Pain Part 1: Pediatric Pain

Chronic pain is a prevalent and persistent problem in middle childhood and adolescence. The biopsychosocial model of pain, which accounts for the complex interplay of the biological, psychological, social, and environmental factors that contribute to and maintain pain symptoms and related disability has guided our understanding and treatment of pediatric pain. Consequently, many interventions for chronic pain are within the realm of rehabilitation, based on the premise that behavior has a broad and central role in pain management. These treatments are typically delivered by one or more providers in medicine, nursing, psychology, physical therapy, and/or occupational therapy. Current data suggest that multidisciplinary treatment is important, with intensive interdisciplinary pain rehabilitation (IIPT) being effective at reducing disability for patients with high levels of functional disability. The following review describes the current state of the art of rehabilitation approaches to treat persistent pain in children and adolescents. Several emerging areas of interventions are also highlighted to guide future research and clinical practice.
Multimodal Behavior Analysis Towards Detecting Mild Cognitive Impairment: Preliminary Results on Gait and Speech

Behavioral analysis for identifying changes in cognitive and physical functioning is expected to help detect dementia such as mild cognitive impairment (MCI) at an early stage. Speech and gait features have been especially recognized as behavioral biomarkers for dementia that possibly occur early in its course, including MCI. However, there are no studies investigating whether exploiting the combination of multimodal behavioral data could improve detection accuracy. In this study, we collected speech and gait behavioral data from Japanese seniors consisting of cognitively healthy adults and patients with MCI. Comparing the models using single modality behavioral data, we showed that the model using multimodal behavioral data could improve detection by up to 5.9%, achieving 82.4% accuracy (chance 55.9%). Our results suggest that the combination of multimodal behavioral features capturing different functional changes resulting from dementia might improve accuracy and help timely diagnosis at an early stage.
Postpartum bonding at the beginning of the second year of child’s life: the role of postpartum depression and early bonding impairment

Abstract Background: We evaluated the association between mother–child bonding and maternal depression at 6–8 months after birth with bonding impairment at 12–15 months in a sample of mothers at high risk of postnatal depression. Methods: A prospective cohort study with 346 low-income postpartum women with antenatal depression. The Postpartum Bonding Questionnaire (PBQ) and the Patient Health Questionnaire-9 (PHQ-9) were used, at 6–8 and 12–15 months after delivery, to assess the mother–infant bonding and postnatal depression (PPD), respectively. Results: The percentage of the main outcome, bonding impairment (BI) at 12–15 months, was 9.9% (95% CI 6.6–13.7). Using logistic regression models, BI was associated with: having an occupation (OR = 2.82; 95% CI 1.00–7.94, p = .049), unplanned pregnancy (OR = 3.46; 95% CI 1.01–11.8, p = .047), and presence of BI at 6–8 months (OR= 13.0; 95% CI 3.76–45.4, p ≤ .001). Maternal depression was marginally associated with BI at 12–15 months. Conclusions: BI affects 1 in 10 mothers, and although BI and PPD are strongly associated at 6–8 and 12–15 months after delivery, BI at 6–8 months is the main predictor of later BI. Based on the study findings, PPD screening in combination with BI assessment is highly recommended during the first year of child’s life.
Modular Multilevel Converters: Analysis, Control, and Applications

High-power multilevel converters are well known in industry and academia as one of the preferred choices for efficient power conversion. Over the past decade, several power converters have been developed and commercialized in the form of standard and customized products that power a wide range of industrial applications. Currently, the modular multilevel converter is a fastgrowing technology and has received wide acceptance from both industry and academia. Providing adequate technical background for graduateand undergraduate-level teaching, this book includes a comprehensive analysis of the conventional and advanced modular multilevel converters employed in motor drives, HVDC systems, and power quality improvement.
Antidiarrheal activity of methanol extract of Sophora tonkinensis in mice and spasmolytic effect on smooth muscle contraction of isolated jejunum in rabbits

Abstract Context: In China, the herb Sophora tonkinensis Gagnep. (Fabaceae, ST) (Committee of National Pharmacopeia. 2015) exhibits anti-inflammatory, antitumor, and antiviral effects. However, to date, there have been few studies on its gastrointestinal effect. Objective: The gastrointestinal effect of the methanol extract of ST rhizome (STR) was evaluated. Materials and methods: Study was conducted from February to December 2018. In vivo, antidiarrheal activity of STR (125, 250 and 500 mg/kg; orally) in castor oil-induced diarrheal mice was studied. In vitro, the effects of STR (0.01–10 mg/mL) on the isolated tissue preparations of rabbit jejunum were also investigated, the rabbit jejunum stripes were pre-contracted with Ach (10−5 M), K+ (60 mM) and tested in the presence of STR, the possible spasmolytic effect was analyzed in the pretreatment of the jejunum preparations with STR or verapamil in Ca2+-free high-K+ (60 mM) solution containing EDTA. Results: STR (125, 250 and 500 mg/kg) exhibited antidiarrheal activity. STR (0.01–10 mg/mL) completely relaxed spontaneously contracting, Ach (10−5 M) and high K+ (60 mM) induced contracted jejunum with an EC50 value of 0.66 (0.49–0.96), 0.39 (0.28–0.44) and 0.17 (0.10–0.21), similar to verapamil. Concentration–response curves of CaCl2 could be significantly moved to the right and down in the presence of STR (0.3, 1 mg/mL). Discussion and conclusions: Results suggest the presence of antidiarrheal activity and spasmolytic effects of STR, possibly mediated through Ca2+ channel blocking activity, providing the pharmacological basis for its traditional uses in gastrointestinal disorders.
Do reduced visual acuity and refractive error affect classroom performance?

The role of visual acuity and refractive errors in the academic performance of children is controversial due to the variable quality of the research in this area and the mixed findings reported. This review aims to provide clarity by reviewing and critiquing relevant peer‐reviewed publications and also summarises what is known regarding the visual demands of modern classroom environments. The outcomes of this review suggest that while a number of studies have investigated the role of vision in relation to children's academic performances, the veracity of the evidence obtained from the majority of these studies is undermined by methodological limitations. Comparisons between studies are constrained by differences in experimental designs, instrumentation and sample characteristics. Despite these limitations, the weight of evidence suggests there is an association between academic performance and both visual acuity and refractive error in children. However, well‐designed experimental studies are necessary to further understand the relationship between these parameters.