Miracle-dz/UniFAR-FTUs huggingface dataset:
In vivo antidiabetic activity of nimesulide due to inhibition of amino acid transport

Inhibiting the intestinal and renal neutral amino acid transporter B0AT1 by genetic means has improved insulin sensitivity in mice, but there are no antagonists available for preclinical or clinical use. Since the anti‐inflammatory agent nimesulide selectively inhibited B0AT1 in vitro, we hypothesized that nimesulide exhibits in vivo potential to restrict neutral amino acid absorption and, therefore, may improve insulin sensitivity. The dose‐related effect of nimesulide (10 to 100 mg/kg, PO) on intestinal absorption of neutral amino acids was estimated in C57 mice. The effect of nimesulide (50 mg/kg, PO) on renal resorption of amino acids was also assessed. The effect of chronic nimesulide (50 mg/kg, PO, BID for 14 days) was assessed in high protein diet‐fed C57 mice, diet‐induced obese mice and obese and diabetic db/db mice. Acute and chronic nimesulide treatment decreased absorption of neutral amino acids and increased their urinary excretion. Nimesulide treatment improved insulin sensitivity and glycemic control, increased GLP‐1, decreased liver lipids and improved FGF‐21 in serum. Nimesulide improved insulin sensitivity and glucose tolerance by inhibiting neutral amino acid transport in the intestine and kidneys. Thus, it can serve as a tool compound for in vivo B0AT1 inhibition.
Clinical Practice Guidelines for Pre-Analytical Procedures of Plasma Epidermal Growth Factor Receptor Variant Testing

Standardization of cell-free DNA (cfDNA) testing processes is necessary to obtain clinically reliable results. The pre-analytical phase of cfDNA testing greatly influences the results because of the low proportion and stability of circulating tumor DNA (ctDNA). In this review, we provide evidence-based clinical practice guidelines for pre-analytical phase procedures of plasma epidermal growth factor receptor gene (EGFR) variant testing. Specific recommendations for pre-analytical procedures were proposed based on evidence from the literature and our experimental data. Standardization of pre-analytical procedures can improve the analytical performance of cfDNA testing.
Degradable inorganic/polymer core-shell microspheres for pH-triggered release of indole-3-acetic acid

Abstract The narrowly dispersed functional silica/poly(di(metacryloylooxy-1-ethoxy) methane-co-acryl amide) (SiO2/P(DMOEM-co-AAm)) core-shell microspheres were synthesized by distillation precipitation polymerization of DMOEM as a degradable crosslinker and AAm as a functional monomer with the presence of 3-(methacryloxy)propyltrimethoxysilane (MPS) modified silica microspheres as seeds. Indole-3-acetic acid (IAA) can be efficiently loaded into the microspheres with a loading capacity of 37.5% via hydrogen-bonding interaction between the carboxylic acid group of IAA and the amide groups on the surface of SiO2/P(DMOEM-co-AAm). The loaded IAA can be triggered released by pH due to the presence of pH-responsive crosslinker (DMOEM). Graphical Abstract
Studies on some physicochemical properties of Rhodanese synthesized by Bacillus cereus isolated from the effluents of iron and steel smelting industry

The study purified and investigated the physicochemical properties of rhodanese (a cyanide detoxifying enzyme) synthesized by Bacillus cereus. This was with a view to producing an industrially important enzyme. The bacterial strain was identified as B. cereus by sequencing of its 16SrRNA gene. B. cereus rhodanese was purified with a fold of 3.53, yield of 36.80% and specific activity of 25.30 µmol/min/mg protein. The molecular weight determined on SDS-PAGE was 33.800 kDa. The enzyme exhibited maximum activity at 9.0 pH and 50°C. The Kms of B. cereus rhodanese for sodium thiosulphate and potassium cyanide were 19.9 ± 1.05 and 31.4 ± 1.55 mM respectively, while Vmax were 6.19 ± 0.40 and 4.83 ± 0.93 RU/ml respectively. The substrate specificity study using different sulphur compounds showed that the enzyme prefers sodium thiosulphate. The enzyme showed stability at a temperature range of 40-50°C. At 10 mM concentration, metals such as (BaCl2, CaCl2, MnCl2, and SnCl2) had little influence on the enzyme activity while NaCl and HgCl2 inhibited enzyme activity. The presence and biochemical properties of B. cereus rhodanese suggest its possible application in cyanide detoxification. Key words: Bacillus cereus, isolate, cyanide, purification, rhodanese, kinetics.
Effects of water on the solvation and structure of lipase in deep eutectic solvents containing a protein destabilizer and stabilizer.

Aqueous deep eutectic solvent (DES) solutions emerge as new media for biocatalysis. The large number of DESs provides a space for designing solutions with desired features. One challenge for this design is to understand the fundamental relationship between the water effect on biocatalysis and the DES compositions. We investigate the solvation and structure of a lipase protein in two DESs containing a protein destabilizer (choline : urea (1 : 2)) and stabilizer (choline : glycerol (1 : 2)) and their 1 : 1 aqueous solution using molecular dynamics simulations. The lipase protein in the pure aqueous solution is simulated as the reference. The lipase protein remains folded in both DESs and their aqueous solutions. In both DESs, water molecules weaken the solvation shell of the lipase protein by reducing the protein-DES hydrogen bond lifetimes. However, the water molecules change the surface area and conformation of the active site on the lipase protein differently in the two DESs. Our simulations indicate that the impact on active sites plays an important role in differentiating the effect of water on biocatalysis in aqueous DESs.
Quality of Sleep in Elderly Patients with Diabetes Mellitus from Turkey: A Cross-Sectional Observational Study

ABSTRACT Background Elderly patients frequently experience poor sleep quality. We aimed to determine its prevalence and risk factors in diabetic elderly patients from Turkey. Methods An observational cross-sectional study of 220 diabetic elderly patients with a mean age of 70.4 ± 5.9 was conducted between June 2019 and December 2019. Pittsburgh Sleep Quality Index (PSQI) questionnaire was used. Patients were divided based on sleep quality into poor (PSQI> 5) and good (PSQI≤ 5) sleep quality groups. Geriatric Depression Scale, Beck Anxiety Inventory, and Hendrich II Fall Risk Model were adopted. The prevalence of poor sleep quality and risk factors were evaluated. Results Prevalence of poor sleep quality was 58.6%. Poor sleepers were significantly older, were more likely to be divorced, had more comorbidities, and used more medicines (ps<0.05). Longer duration of diabetes, higher incidence of hypoglycemic events, and diabetic complications were significantly associated with poor sleep quality (ps<0.05). Poor sleepers had higher levels of blood glucose and HbA1c levels (ps<0.05). PSQI was significantly correlated with age, HbA1c, duration of diabetes, higher depression, anxiety, and falling risk (ps<0.05). Severe depression, anxiety, and higher falling risk were independent risk factors. Conclusion Most patients experienced poor sleep quality. It was associated with a longer duration of diabetes, chronic diabetes-related complications, and higher HbA1c levels. Severe depression, anxiety, and higher falling risk were risk factors for poor sleep quality.
Diagnostic Characteristics of Urinary Red Blood Cell Distribution Incorporated in UF-5000 for Differentiation of Glomerular and Non-Glomerular Hematuria

Background Automated urine sediment analysis has been developed to address the limitations of microscopic examination of dysmorphic red blood cells (RBCs). We evaluated the urinary RBC distribution (URD) parameter of a recently launched automated urinary flow cytometry analyzer, UF-5000 (Sysmex, Kobe, Japan), to differentiate glomerular hematuria (GH) from non-GH (NGH). Methods Samples submitted for urine sediment analysis from patients with hematuria (>20 RBCs/μL) were divided into derivation (N=156; 101 GH, 55 NGH) and validation cohorts (N=107; 60 GH, 47 NGH). The clinical diagnosis of GH or NGH was established based on clinical data review. Differences in UF-5000 parameters (URD, small RBC, lysed RBC, RBC-P70FSC, RBC-SF-FSC-W, mean forward-scattered light, and mean side-scattered light) between GH and NGH, and areas under the ROC curves (AUC) were analyzed in the derivation cohort. The derived ideal cut-off value was evaluated in the validation cohort. We applied the Kitasato criteria to compare the diagnostic performance. Results URD (%), differed significantly between GH and NGH (P<0.001) in the two cohorts. The AUC of URD was 0.814 and 0.806 in the derivation and validation cohorts, respectively. Using a cut-off of >20.1%, the sensitivity was 99.0%/89.4% and the specificity was 50.9%/63.3% in the derivation/validation cohort. When the Kitasato criteria were applied, the sensitivity and specificity were 80.2% and 52.7%, respectively. Conclusions URD is a rapid, objective, and quantitative measure that can be used to differentiate GH and NGH.
Dexmedetomidine Added to Ropivacaine for Ultrasound-guided Erector Spinae Plane Block Prolongs Analgesia Duration and Reduces Perioperative Opioid Consumption After Thoracotomy

Objectives: Single-injection erector spinae plane block (ESPB) provides good control of pain relief after open thoracotomy surgeries. However, the duration of pain relief does not last long. For this purpose, we hypothesized that adding α2-adrenoceptor agonist, dexmedetomidine, for interfascial nerve blockade may increase the duration of analgesia. There are only few studies using dexmedetomidine for interfasical nerve blocks in humans. In this study, our aim is to investigate whether addition of dexmedetomidine to ropivacaine for ESPB could effectively prolong the duration of postoperative analgesia and reduce opioid consumption after open thoracotomy. Materials and Methods: Sixty patients with esophageal cancer were randomized to receive ESPB using 28 mL of 0.5% ropivacaine, with 2 mL of normal saline (group R) or 0.5 µg/kg dexmedetomidine in 2 mL (group RD) administered interfascially. ESPB was performed at the fifth thoracic level under ultrasound guidance. The primary outcome was the duration of analgesia. The secondary outcomes were total postoperative sufentanil consumption, Numeric Rating Scale pain scores, Ramsay Sedation Scale scores and adverse effects. Results: The duration of analgesia in group RD (505.1±113.9) was longer than that in group R (323.2±75.4) (P<0.001). The total postoperative sufentanil consumption was lower in group RD (23.3±10.0) than in group R (33.8±13.8) (P=0.001). There was no significant difference in the incidence of adverse effects between the 2 groups. Conclusion: After open thoracotomy, addition of dexmedetomidine to ropivacaine for ESPB effectively prolonged the duration of postoperative analgesia and reduced opioid consumption without increasing additional incidence of adverse effects.
Chronic lymphocytic leukemia in China

Chronic lymphocytic leukemia (CLL) is 10to 20-fold less common in Han Chinese in China compared with persons of predominately European descent translating to incidences of 0.2 to 0.6 per 10E+5 population/year vs. 4.6 per 10E+5 population/year. Reason(s) for this markedly lower incidence and therefore prevalence in China is unknown but is shared with the other Asian nationalities including Japanese, Koreans, and others. Studies of large cohorts of Chinese with CLL are relatively rare and there are no population-based studies in the mainland of China. Several seeming differences between CLL in Chinese and persons of predominately European descent are reported such as younger age at diagnosis, different background genotypes, increased frequency of IGHV mutation, different stereotype use and different mutation topographies. However, in general, most cases of CLL in Han Chinese are like CLL in persons of predominately European descent.
Prevalence and factors associated with urinary incontinence in females with cystic fibrosis: An Italian single‐center cross‐sectional analysis

Individuals with cystic fibrosis (CF) are deemed to have a higher risk of developing urinary incontinence (UI), likely due to repeated increasing pressure on the pelvic floor. We aimed to determine the prevalence of female UI in a large CF referral center, and to assess the association between UI and severity of CF disease.
Knowledge, attitudes and practices of health professionals towards people living with lymphoedema caused by lymphatic filariasis, podoconiosis and leprosy in northern Ethiopia

Abstract Background Podoconiosis, lymphatic filariasis and leprosy are highly stigmatised neglected tropical diseases that cause lymphoedema. Their enormous impacts on health-related quality of life, mental health and economic productivity can be significantly reduced by morbidity management and disability prevention (MMDP) services, but to deliver such services requires appropriate training of healthcare professionals. The aim of this study was to assess the knowledge, attitudes and practices (KAP) of rural Ethiopian healthcare professionals towards people with lymphoedema as a way to assess training needs. Methods This study used questionnaires to quantitatively assess KAP towards people with lymphoedema among rural healthcare professionals in northwest Ethiopia before and 12 months after a short training intervention. Results Questionnaires were administered to 14 health professionals at baseline and 21 at follow-up. At baseline, 71% (10/14) were found to hold at least one stigmatising attitude towards lymphoedema patients, compared with 66% (14/21) at follow-up. Large gaps in knowledge were noted, with many unable to identify ways of treating/preventing the diseases. Conclusions This study showed high proportions of healthcare workers holding stigmatising views and lacking essential knowledge about lymphoedema. To maximise the impact of MMDP interventions, further research is urgently needed to understand how to address these issues.
Alcohol, smoking, recreational drug use and association with virological outcomes among people living with HIV: cross‐sectional and longitudinal analyses

There is increasing evidence to suggest that people living with HIV (PLWH) have significant morbidity from alcohol, recreational drug use and cigarette smoking. Our aim was to report associations of these factors with antiretroviral therapy (ART) non‐adherence, viral non‐suppression and subsequent viral rebound in PLWH.
Diverse functional elements in RNA predicted transcriptome-wide by orthogonal RNA structure probing

Abstract RNA molecules can fold into complex structures and interact with trans-acting factors to control their biology. Recent methods have been focused on developing novel tools to measure RNA structure transcriptome-wide, but their utility to study and predict RNA-protein interactions or RNA processing has been limited thus far. Here, we extend these studies with the first transcriptome-wide mapping method for cataloging RNA solvent accessibility, icLASER. By combining solvent accessibility (icLASER) with RNA flexibility (icSHAPE) data, we efficiently predict RNA-protein interactions transcriptome-wide and catalog RNA polyadenylation sites by RNA structure alone. These studies showcase the power of designing novel chemical approaches to studying RNA biology. Further, our study exemplifies merging complementary methods to measure RNA structure inside cells and its utility for predicting transcriptome-wide interactions that are critical for control of and regulation by RNA structure. We envision such approaches can be applied to studying different cell types or cells under varying conditions, using RNA structure and footprinting to characterize cellular interactions and processing involving RNA.
Early Enteral Nutrition and Gastrointestinal Complications in Pediatric Patients on Extracorporeal Membrane Oxygenation

ABSTRACT Objectives: To assess the safety of enteral nutrition (EN) in children on extracorporeal membrane oxygenation (ECMO). To describe nutritional status and the characteristics of the nutritional support in this population. Methods: A retrospective single-center analysis (2006–2016) including children <18 years on ECMO. Demographic data, nutritional status, characteristics of nutritional support, and development of gastrointestinal (GI) complications were recorded. Results: One hundred children, with a median age of 9.7 months (interquartile range [IQR] 3.9–63.1) were enrolled. Undernutrition was prevalent among children on ECMO (33.3%) mainly in patients <2 years (P = 0.042). Most patients (64%) received EN at some point during ECMO therapy. EN was administered in the first 48 hours after ECMO initiation (48HEN) to 60.3% of the children. Mortality rate in the Pediatric Intensive Care Unit was lower in patients who received EN as the initial artificial nutrition support (ANS) (37.7 vs 51%, P = 0.005) and in children on 48HEN (34% vs 50%, P = 0.04). In the logistic regression analysis, duration of ECMO support and low cardiac output indication were the only factors associated with mortality. Although most patients on ECMO (45%) developed digestive complications, they were mostly mild, being constipation the most prevalent. In the logistic regression analysis, EN was not associated with an increase in GI complications (P = 0.09). Only three patients developed intestinal ischemia (one without EN and two on EN). Conclusions: Undernutrition is prevalent among children on ECMO, mainly in infants <2 years. EN is not associated with severe gastrointestinal complications or higher mortality in these children.
Evidence of a shared binding site for Bacillus thuringiensis Cry1Ac and Cry2Aa toxins in Cnaphalocrocis medinalis cadherin

Insect midgut cadherins function as receptors and play critical roles as protein receptors of insecticidal Bacillus thuringiensis (Bt) toxins used as biopesticides and in Bt transgenic crops worldwide. Here, we cloned and characterized the full‐length midgut cadherin (CmCad) cDNA from the rice leaffolder (Cnaphalocrocis medinalis), a destructive pest of rice in many Asian countries. Expression of recombinant proteins corresponding to the extracellular domain of CmCad allowed testing binding of Cry proteins. Results from in vitro ligand blotting and enzyme‐linked immunosorbent assays supported that the extracellular domain of CmCad contains regions recognized by both Cry1Ac and Cry2Aa. Molecular modelling and docking simulations indicated that binding to both Cry1Ac and Cry2Aa is localized primarily within a CmCad motif corresponding to residues T1417–D1435. A recombinant CmCad protein produced without residues T1417–D1435 lacked binding to Cry1Ac and Cry2Aa, confirmed our modelling predictions that CmCad has a shared Cry1Ac and Cry2Aa binding site. The potential existence of a shared binding region in CmCad suggests that caution should be taken when using combinations of Cry1Ac and Cry2Aa in pyramided transgenic rice, as their combined use could speed the evolution of resistance to both toxins.
Patterns of menstrual cycle length over the menopause transition are associated with subclinical atherosclerosis after menopause

Abstract Objective: Longer menstrual cycles have been associated with greater risk of cardiovascular disease, supporting a contribution of abnormal ovarian function. We aimed to characterize trajectories of menstrual cycle length over the menopause transition (MT) and test whether these trajectories are associated with postmenopausal markers of subclinical atherosclerosis. Methods: Women from the Study of Women's Health Across the Nation Daily Hormone Study were included if they had an observed date of the final menstrual period (FMP), recorded cycle lengths from ≥2 annual menstrual cycles (mean±SD: 4.22 ± 1.91 cycles), and had measurements of postmenopausal carotid intima-media thickness (cIMT) and/or brachial-ankle pulse wave velocity (baPWV). Trajectories of cycle length over the MT were identified using group-based trajectory modeling and linked with cIMT and baPWV using linear regression. Results: We studied 428 women who had 1,808 cycles over the MT (45.1 ± 2.3 y old at baseline visit), and of whom 263 had cIMT, and 213 had baPWV measured postmenopausally (after 13.88 ± 0.42 and 15.25 ± 0.70 y since baseline visit, respectively). Three distinct trajectories of cycle length were identified: stable (no changes in cycle length over the MT among 62.1% of women), late increase (a late increase 2 y before the FMP among 21.8%), and early-increase (an early increase 5 y before the FMP among 16.2%). Women with the late-increase pattern had significantly lower postmenopausal cIMT (0.72 mm) and baPWV (1392 cm/s) levels than the stable group (0.77 mm and 1508 cm/s, respectively) adjusting for race, concurrent age, socioeconomic status, physical activity level, and premenopausal cardiovascular risk profile. Conclusions: Patterns of cycle length over the MT seem to be a marker of future vascular health that may help identify groups at greater or lesser risk of atherosclerosis after menopause.
Quality of Care and Outcomes Among a Diverse Group of Long-Term Care Residents With Alzheimer’s Disease and Related Dementias

Objectives This article assessed whether disparities among ADRD Medicare beneficiaries existed in five different long-stay quality measures. Methods: We linked individual-level data and facility-level characteristics. The main quality outcomes included whether residents: 1) were assessed/appropriately given the seasonal influenza vaccine; 2) received an antipsychotic medication; 3) experienced one/more falls with major injury; 4) were physically restrained; and 5) lost too much weight. Results: In 2016, there were 1,005,781 Medicare Advantage and fee-for-service long-term residents. About 78% were White, 13% Black, 2% Asian/Pacific Islander (Asian/PI), 6% Hispanic, and 0.4% American Indian/Alaska Native (AI/AN). Whites reported higher use of antipsychotic medications along with Hispanics and AI/AN (28%, 28%, and 27%, respectively). Similarly, Whites and AIs/ANs reported having one/more falls compared to the other groups (9% and 8%, respectively). Discussion: Efforts to understand disparities in access and quality of care among American Indians/Alaska Natives are needed, especially post-pandemic.
Elimination of hepatitis B virus infection in children: experience and challenge in China

Abstract Chronic hepatitis B virus (HBV) infection is a serious health issue because of its severe sequelae. Prevention of mother-to-child transmission (MTCT) of HBV is critical to eliminate chronic HBV infection. Here, we reviewed the progress toward the elimination of HBV infection in children in China in the recent decade. A universal hepatitis B vaccination program started from 2002 has been intensified, with the coverage of timely birth dose >95% of all newborn infants from 2012. Since 2011, China has taken a nationwide program to administer hepatitis B immunoglobulin (HBIG) with free of charge in all neonates of HBV-infected mothers, leading to a significant increment of timely use of HBIG. The prevalence of hepatitis B surface antigen (HBsAg) was declined from around 10% among children in 1980s to <0.5% among children born after 2011. Administration of oral antiviral agents in HBV-infected pregnant women with HBV DNA >2 × 105 U/mL during the third trimester is increasing, which will further reduce MTCT of HBV. However, there are some challenges in the elimination of HBV infection in children, which need to overcome by the concerted efforts. Nevertheless, it is anticipated that China will achieve the goal set by the World Health Organization that the prevalence of HBsAg in children aged <5 years is ≤0.1% by 2030.