Ultrastrong spinodoid alloys enabled by electrochemical dealloying and refilling.

We present an extreme case of composition-modulated nanomaterial formed by selective etching (dealloying) and electrochemical refilling. The product is a coarse-grain polycrystal consisting of two interwoven nanophases, with identical crystal structures and a cube-on-cube relationship, separated by smoothly curved semicoherent interfaces with high-density misfit dislocations. This material resembles spinodal alloys structurally, but its synthesis and composition modulation are spinodal-independent. Our Cu/Au "spinodoid" alloy demonstrates superior mechanical properties such as near-theoretical strength and single-phase-like behavior, owing to its fine composition modulation, large-scale coherence of crystal lattice, and smoothly shaped three-dimensional (3D) interface morphology. As a unique extension of spinodal alloy, the spinodoid alloy reported here reveals a number of possibilities to modulate the material's structure and composition down to the nanoscale, such that further improved properties unmatchable by conventional materials can be achieved.

Understanding the Neural Mechanisms of General Anesthesia from Interaction with Sleep-Wake State: A Decade of Discovery.

The development of cutting-edge techniques to study specific brain regions and neural circuits that regulate sleep-wake brain states and general anesthesia (GA), has increased our understanding of these states that exhibit similar neurophysiologic traits. This review summarizes current knowledge focusing on cell subtypes and neural circuits that control wakefulness, rapid eye movement (REM) sleep, non-REM sleep, and GA. We also review novel insights into their interactions and raise unresolved questions and challenges in this field. Comparisons of the overlapping neural substrates of sleep-wake and GA regulation will help us to understand sleep-wake transitions and how anesthetics cause reversible loss of consciousness. SIGNIFICANCE STATEMENT: General anesthesia (GA), sharing numerous neurophysiologic traits with the process of natural sleep, is administered to millions of surgical patients annually. In the past decade, studies exploring the neural mechanisms underlying sleep-wake and GA have advanced our understanding of their interactions and how anesthetics cause reversible loss of consciousness. Pharmacotherapies targeting the neural substrates associated with sleep-wake and GA regulations have significance for clinical practice in GA and sleep medicine.

Downregulation of JAM3 occurs in cholangiocarcinoma by hypermethylation: A potential molecular marker for diagnosis and prognosis.

Junctional adhesion molecular 3 (JAM3) is downregulated by hypermethylation in cancers but is unclear in cholangiocarcinoma. The JAM3 expression level was checked in cholangiocarcinoma cell lines and tissues. Methylated JAM3 was detected in cell lines, tissues and plasma cell-free DNAs (cfDNA). The roles of JAM3 in cholangiocarcinoma were studied by transfection of siRNA and pCMV3-JAM3. The survival analysis was based on the Gene Set Cancer Analysis (GSCA) database. JAM3 was downregulated in HCCC-9810 and HuCCT1 cell lines and tissues by hypermethylation. Methylated JAM3 was detected in cfDNAs with 53.3% sensitivity and 96.6% specificity. Transfection of pCMV3-JAM3 into HCCC-9810 and HuCCT1 induced apoptosis and suppressed cell proliferation, migration and invasion. The depletion of JAM3 in RBE cells using siRNA decreased apoptosis and increased cell proliferation, migration and invasion. Hypermethylation of JAM3 was associated with tumour differentiation, metastasis and TNM stage. Downregulation and hypermethylation of JAM3 were related to poor progression-free survival. Junctional adhesion molecular 3 may function as a tumour suppressor in cholangiocarcinoma. Methylated JAM3 DNA may represent a non-invasive molecular marker for the early detection of cholangiocarcinoma and prognosis.

The neutrophil extracellular traps in neurological diseases: An update.

Neutrophil extracellular traps released by neutrophils are web-like DNA structures adhered to granulin proteins with bactericidal activity and can be an important mechanism for preventing pathogen dissemination or eliminating microorganisms. However, they also play important roles in diseases of other systems, such as the central nervous system. We tracked the latest advances and performed a review based on published original and review articles related to neutrophil extracellular traps and neurological diseases. Generally, neutrophils barely penetrate the blood-brain barrier into the brain parenchyma, but when pathological changes such as infection, trauma, or neurodegeneration occur, neutrophils rapidly infiltrate the central nervous system to exert their defensive effects. However, neutrophils may adversely affect the host when they uncontrollably release neutrophil extracellular traps upon persistent neuroinflammation. This review focused on recent advances in understanding the mechanisms and effects of neutrophil extracellular traps release in neurological diseases, and we also discuss the role of molecules that regulate neutrophil extracellular traps release in anticipation of clinical applications in neurological diseases.

Predictors of improvement in left ventricular systolic function after catheter ablation in patients with persistent atrial fibrillation complicated with heart failure.

AIMS: The current management of patients with atrial fibrillation (AF) and concomitant heart failure (HF) remains a significant challenge. Catheter ablation (CA) has been shown to improve left ventricular ejection fraction (LVEF) in these patients, but which patients can benefit from CA is still poorly understood. The aim of our study was to determine the predictors of improved ejection fraction in patients with persistent atrial fibrillation (PeAF) complicated with HF undergoing CA. METHODS AND RESULTS: A total of 435 patients with persistent AF underwent an initial CA between January 2019 and March 2023 in our hospital. We investigated consecutive patients with left ventricular systolic dysfunction (LVEF < 50%) measured by transthoracic echocardiography (TTE) within one month before CA. According to the LVEF changes at 6 months, these patients were divided into an improved group (fulfilling the '2021 Universal Definition of HF' criteria for LVEF recovery) and a nonimproved group. Eighty patients were analyzed, and the improvement group consisted of 60 patients (75.0%). In the univariate analysis, left ventricular end-diastolic diameter (P = 0.005) and low voltage zones in the left atrium (P = 0.043) were associated with improvement of LVEF. A receiver operating characteristic analysis determined that the suitable cutoff value for left ventricular end-diastolic diameter (LVDd) was 59 mm (sensitivity: 85.0%, specificity: 55.0%, area under curve: 0.709). A multivariate analysis showed that LVDd (OR = 0.85; 95% CI: 0.76-0.95, P = 0.005) and low voltage zones (LVZs) (OR = 0.26; 95% CI: 0.07-0.96, P = 0.043) were significantly independently associated with the improvement of LVEF. Additionally, parameters were significantly improved regarding the left atrial diameter, LVDd and ventricular rate after radiofrequency catheter ablation (all p < 0.05). CONCLUSIONS: The improvement of left ventricular ejection fraction (LVEF) occurred in 75.0% of patients. Our study provides additional evidence that LVDd < 59 mm and no low voltage zones in the left atrium can be used to jointly predict the improvement of LVEF after atrial fibrillation ablation.

Ac2-26 activated the AKT1/GSK3ß pathway to reduce cerebral neurons pyroptosis and improve cerebral function in rats after cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) results in brain injury, which is primarily caused by inflammation. Ac2-26 protects against ischemic or hemorrhage brain injury. The present study was to explore the effect and mechanism of Ac2-26 on brain injury in CPB rats. METHODS: Forty-eight rats were randomized into sham, CPB, Ac, Ac/AKT1, Ac/GSK3ßi and Ac/AKT1/GSK3ßa groups. Rats in sham group only received anesthesia and in the other groups received standard CPB surgery. Rats in the sham and CPB groups received saline, and rats in the Ac, Ac/AKT1, Ac/GSK3ßi and Ac/AKT1/GSK3ßa groups received Ac2-26 immediately after CPB. Rats in the Ac/AKT1, Ac/GSK3ßi and Ac/AKT1/GSK3ßa groups were injected with shRNA, inhibitor and agonist of GSK3ß respectively. The neurological function score, brain edema and histological score were evaluated. The neuronal survival and hippocampal pyroptosis were assessed. The cytokines, activity of NF-κB, S100 calcium-binding protein ß(S100ß) and neuron-specific enolase (NSE), and oxidative were tested. The NLRP3, cleaved-caspase-1 and cleaved-gadermin D (GSDMD) in the brain were also detected. RESULTS: Compared to the sham group, all indicators were aggravated in rats that underwent CPB. Compared to the CPB group, Ac2-26 significantly improved neurological scores and brain edema and ameliorated pathological injury. Ac2-26 reduced the local and systemic inflammation, oxidative stress response and promoted neuronal survival. Ac2-26 reduced hippocampal pyroptosis and decreased pyroptotic proteins in brain tissue. The protection of Ac2-26 was notably lessened by shRNA and inhibitor of GSK3ß. The agonist of GSK3ß recovered the protection of Ac2-26 in presence of shRNA. CONCLUSIONS: Ac2-26 significantly improved neurological function, reduced brain injury via regulating inflammation, oxidative stress response and pyroptosis after CPB. The protective effect of Ac2-26 primarily depended on AKT1/ GSK3ß pathway.

The role of TGF-ß signaling in muscle atrophy, sarcopenia and cancer cachexia.

Skeletal muscle, comprising a significant proportion (40 to 50 percent) of total body weight in humans, plays a critical role in maintaining normal physiological conditions. Muscle atrophy occurs when the rate of protein degradation exceeds protein synthesis. Sarcopenia refers to age-related muscle atrophy, while cachexia represents a more complex form of muscle wasting associated with various diseases such as cancer, heart failure, and AIDS. Recent research has highlighted the involvement of signaling pathways, including IGF1-Akt-mTOR, MuRF1-MAFbx, and FOXO, in regulating the delicate balance between muscle protein synthesis and breakdown. Myostatin, a member of the TGF-ß superfamily, negatively regulates muscle growth and promotes muscle atrophy by activating Smad2 and Smad3. It also interacts with other signaling pathways in cachexia and sarcopenia. Inhibition of myostatin has emerged as a promising therapeutic approach for sarcopenia and cachexia. Additionally, other TGF-ß family members, such as TGF-ß1, activin A, and GDF11, have been implicated in the regulation of skeletal muscle mass. Furthermore, myostatin cooperates with these family members to impair muscle differentiation and contribute to muscle loss. This review provides an overview of the significance of myostatin and other TGF-ß signaling pathway members in muscular dystrophy, sarcopenia, and cachexia. It also discusses potential novel therapeutic strategies targeting myostatin and TGF-ß signaling for the treatment of muscle atrophy.

Construction of a predictive model for new-onset atrial fibrillation after acute myocardial infarction based on P-wave amplitude in lead V1.

BACKGROUND: In this study, we aimed to identify the risk factors for new-onset atrial fibrillation (NOAF) after postcoronary intervention in patients with acute myocardial infarction (AMI) and to establish a nomogram prediction model. METHODS: The clinical data of 506 patients hospitalized for AMI from March 2020 to February 2023 were retrospectively collected, and the patients were randomized into a training cohort (70%; n = 354) and a validation cohort (30%; n = 152). Independent risk factors were determined using least absolute shrinkage and selection operator and multivariate logistic regression. Predictive nomogram modeling was performed using R software. Nomograms were evaluated based on discrimination, correction, and clinical efficacy using the C-statistic, calibration plot, and decision curve analysis, respectively. RESULTS: The multivariate logistic regression analysis showed that P-wave amplitude in lead V1, age, and infarct type were independent risk factors for NOAF, and the area under the receiver operating characteristic curve of the training and validation sets was 0.760 (95% confidence interval [CI] 0.674-0.846) and 0.732 (95% CI 0.580-0.883), respectively. The calibration curves showed good agreement between the predicted and observed values in both the training and validation sets, supporting that the actual predictive power was close to the ideal predictive power. CONCLUSIONS: P-wave amplitude in lead V1, age, and infarct type were independent risk factors for NOAF in patients with AMI after intervention. The nomogram model constructed in this study can be used to assess the risk of NOAF development and has some clinical application value.

Efficient removal of tetracycline and Cu2+ by honeycomb derived magnetic carbon: Adsorption mechanism and advanced oxidation regeneration mechanism.

The honeycomb magnetic carbons (xFe@HCNs) were prepared by sacrificial template method novelty using polyacrylamide resin (PAAS) as template and ammonium pyrrolidine dithioate/Fe3+ complex (APDC-Fe) as carbon skeleton and metal source. Tetracycline (TC) and copper (Cu2+) as target pollutants were used to investigate the adsorption properties of xFe@HCNs in single or binary TC and Cu2+ systems. The adsorption capacity sequence for TC among the adsorbents was (mmol·g-1): 2Fe@HCNs (0.088) > 8Fe@HCNs (0.061) > HCNs (0.054) > RC (0.036), and for Cu2+ was (mmol·g-1): 2Fe@HCNs (1.120) > 8Fe@HCNs (1.026) > RC (0.792) > HCNs (0.681). 2Fe@HCNs demonstrated notable affinity for adsorbing both TC and Cu2+. Additionally, the influence of hydrochemical factors (i.e., cation species, anion species, and pH) on the adsorption properties of 2Fe@HCNs. Combined with advanced oxidation technology, the regeneration methods of magnetic adsorbent were explored using oxidizing agents (e.g., H2O2 and peroxymonosulfate) as eluents which could increase the adsorption sites of magnetic carbon adsorbents during the regenerating process, which was the novelty of the study. Furthermore, the regeneration mechanisms of H2O2 as eluent were investigated. This study discussed the application and regeneration methods of magnetic adsorbents in water treatment, offering new insights into environmental remediation using magnetic materials.

EphB3 protein is a potential ancillary diagnostic biomarker for thyroid cancers.

OBJECTIVE: To investigate the expression of ephrin type B receptor 3 (EphB3) in thyroid tumors and its usage as an ancillary diagnostic biomarker for thyroid tumors. METHODS: Formalin-fixed and paraffin-embedded (FFPE) tissue samples (78 cases) and FNAC samples (57 cases) were assessed with the EphB3 antibody using immunohistochemistry. PTC and other thyroid follicular tumors were compared regarding their EphB3 expression. Sanger sequencing was used to assess for the presence of a BRAF V600E mutation. RESULTS: EphB3 was positive in 81.8 % (27/33) of papillary thyroid carcinoma (PTC), 83.3 % (5/6) of medullary thyroid carcinoma (MTC), 25 % (1/4) of hyperplastic/adenomatoid nodule (HN), 14.3 % (1/7) of follicular adenoma (FA), and negative in follicular tumors of uncertain malignant potential (FT-UMP) (0/13), noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) (0/7), thyroid follicular carcinoma (TFC) (0/4), Hashimoto's thyroiditis (0/4), and normal thyroid follicular tissues (0/33). In cellular blocks, EphB3 was positive in 87.1 % (20/23) of PTC, 75 % (3/4) of MTC, 20 % (2/10) of HN, and negative in atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (0/20) and normal thyroid follicular cells (0/10). CONCLUSION: EphB3 is expressed in the majority of PTC, but less so in benign follicular nodules. EphB3 expression in fine needle aspiration cytology (FNAC) specimens can be used as a diagnostic tool to differentiate thyroid cancer from other follicular lesions in its differential diagnosis, especially AUS/FLUS and PTC.

Association of type 2 diabetes mellitus with dementia-related and non-dementia-related mortality among postmenopausal women: A secondary competing risks analysis of the women's health initiative.

INTRODUCTION: Alzheimer's disease (AD) and AD-related dementias (ADRD) are leading causes of death among older adults in the United States. Efforts to understand risk factors for prevention are needed. METHODS: Participants (n = 146,166) enrolled in the Women's Health Initiative without AD at baseline were included. Diabetes status was ascertained from self-reported questionnaires and deaths attributed to AD/ADRD from hospital, autopsy, and death records. Competing risk regression models were used to estimate the cause-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for the prospective association of type 2 diabetes mellitus (T2DM) with AD/ADRD and non-AD/ADRD mortality. RESULTS: There were 29,393 treated T2DM cases and 8628 AD/ADRD deaths during 21.6 (14.0-23.5) median (IQR) years of follow-up. Fully adjusted HRs (95% CIs) of the association with T2DM were 2.94 (2.76-3.12) for AD/ADRD and 2.65 (2.60-2.71) for the competing risk of non-AD/ADRD mortality. DISCUSSION: T2DM is associated with AD/ADRD and non-AD/ADRD mortality. HIGHLIGHTS: Type 2 diabetes mellitus is more strongly associated with Alzheimer's disease (AD)/AD and related dementias (ADRD) mortality compared to the competing risk of non-AD/ADRD mortality among postmenopausal women. This relationship was consistent for AD and ADRD, respectively. This association is strongest among participants without obesity or hypertension and with younger age at baseline, higher diet quality, higher physical activity, higher alcohol consumption, and older age at the time of diagnosis of type 2 diabetes mellitus.

Association of calcium and vitamin D supplementation with cancer incidence and cause-specific mortality in Black women: Extended follow-up of the Women's Health Initiative calcium-vitamin D trial.

Low circulating vitamin D levels are more prevalent in Black than White individuals. We analyzed the Women's Health Initiative (WHI) calcium plus vitamin D (CaD) randomized clinical trial extended follow-up data to evaluate associations between calcium plus vitamin D supplementation and incident cancer, cardiovascular disease (CVD), and cause-specific mortality endpoints among Black women. Intent-to-treat analysis was performed. Among 3325 Black women in the CaD trial who were randomized into either daily calcium (1000 mg of calcium carbonate) plus vitamin D (400 IU D3) or placebos for an average of 7 years, there were 813 deaths, 588 incident cancers, and 837 CVD events during an average of 15.7 years of follow up (52 230 total person-years). Using Cox's proportional hazards models, we calculated hazard ratios and their confidence intervals for outcomes ascertained during the trial period, posttrial follow-up period and overall periods combined. We found that total mortality, cause-specific mortality, and total cancer incidence were almost identical between CaD and placebo groups. These results suggest that calcium plus vitamin D supplementation does not reduce risks of cancer, CVD, or other major causes of death in Black women overall and, thus, other medical, behavioral or social interventions should be considered to narrow health disparities related to these outcomes. However, other finer endpoints, such as colorectal cancer, warrants further investigation.

Plant-based diets, genetic predisposition and risk of non-alcoholic fatty liver disease.

BACKGROUND: Diets rich in plant-based foods are associated with lower risks of non-alcoholic fatty liver disease (NAFLD), while the prospective evidence is limited. We aimed to examine longitudinal associations of plant-based diets and genetic susceptibility with NAFLD risk. METHODS: This longitudinal cohort study included 159,222 participants (58.0 ± 8.0 years old, 55.7% female) free of NAFLD in the UK Biobank. We calculated the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI). New-onset NAFLD was the primary outcome. The weighted polygenic risk score was calculated based on risk variants associated with NAFLD. Hazard ratios (HR) and 95% confidential intervals (CI) were estimated by Cox proportional hazards model. Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) measured liver fat content in a subsample of 20,692 participants (57.5 ± 7.4 years old, 52.6% female) was the secondary outcome. The associations between plant-based diet indices and MRI-PDFF were evaluated using generalized linear models. RESULTS: During a median follow-up of 9.5 years, 1541 new-onset NAFLD cases were documented. Compared to the lowest quintile, multivariable-adjusted hazard ratios (HRs) of NAFLD in the highest quintile were 0.78 (95% confidential intervals [CI], 0.66-0.93, p-trend =0.02), 0.74 (95% CI, 0.62-0.87, p-trend <0.0001), and 1.24 (95% CI, 1.05-1.46, p-trend = 0.02) for overall PDI, hPDI, and uPDI, respectively. For liver fat content, higher overall PDI and hPDI were associated with lower MRI-PDFF, while higher uPDI was associated with higher liver fat content. We observed a significant interaction between hPDI and PRS (p-interaction =0.03), and the NAFLD risk was lowest among participants with the highest hPDI and low genetic risk. CONCLUSIONS: Higher intake of plant-based diets especially healthful plant-based diets was associated with lower NAFLD risk and liver fat content regardless of genetic susceptibility, whereas an unhealthful plant-based diet was associated with higher NAFLD risk and intrahepatic steatosis. These results suggest that the quality of plant-based foods should be highlighted when adopting a plant-based diet.

Precision Therapy of Recurrent Breast Cancer through Targeting Different Malignant Tumor Cells with a HER2/CD44-Targeted Hydrogel Nanobot.

Heterogeneity and drug resistance of tumor cells are the leading causes of incurability and poor survival for patients with recurrent breast cancer. In order to accurately deliver the biological anticancer drugs to different subtypes of malignant tumor cells for omnidirectional targeted treatment of recurrent breast cancer, a distinct design is demonstrated by embedding liposome-based nanocomplexes containing pro-apoptotic peptide and survivin siRNA drugs (LPR) into Herceptin/hyaluronic acid cross-linked nanohydrogels (Herceptin-HA) to fabricate a HER2/CD44-targeted hydrogel nanobot (named as ALPR). ALPR delivered cargoes to the cells overexpressing CD44 and HER2, followed by Herceptin-HA biodegradation, subsequently, the exposed lipid component containing DOPE fused with the endosomal membrane and released peptide and siRNA into the cytoplasm. These experiments indicated that ALPR can specifically deliver Herceptin, peptide, and siRNA drugs to HER2-positive SKBR-3, triple-negative MDA-MB-231, and HER2-negative drug-resistant MCF-7 human breast cancer cells. ALPR completely inhibited the growth of heterogeneous breast tumors via multichannel synergistic effects: disrupting mitochondria, downregulating the survivin gene, and blocking HER2 receptors on the surface of HER2-positive cells. The present design overcomes the chemical drug resistance and opens a feasible route for the combinative treatment of recurrent breast cancer, even other solid tumors, utilizing different kinds of biological drugs.

Halide perovskites enable polaritonic XY spin Hamiltonian at room temperature.

Exciton polaritons, the part-light and part-matter quasiparticles in semiconductor optical cavities, are promising for exploring Bose-Einstein condensation, non-equilibrium many-body physics and analogue simulation at elevated temperatures. However, a room-temperature polaritonic platform on par with the GaAs quantum wells grown by molecular beam epitaxy at low temperatures remains elusive. The operation of such a platform calls for long-lifetime, strongly interacting excitons in a stringent material system with large yet nanoscale-thin geometry and homogeneous properties. Here, we address this challenge by adopting a method based on the solution synthesis of excitonic halide perovskites grown under nanoconfinement. Such nanoconfinement growth facilitates the synthesis of smooth and homogeneous single-crystalline large crystals enabling the demonstration of XY Hamiltonian lattices with sizes up to 10 × 10. With this demonstration, we further establish perovskites as a promising platform for room temperature polaritonic physics and pave the way for the realization of robust mode-disorder-free polaritonic devices at room temperature.

Fiber-based high-speed 3D schlieren imaging.

This Letter reports the first demonstration of a high-speed three-dimensional (3D) schlieren technique based on the combination of fiber imaging, Toepler's lens-type schlieren, and computed tomography (CT). The technique uses a single high-speed camera, two xenon lamps, and a series of fiber bundles to simultaneously capture the schlieren images of turbulent flames from seven orientations with a framerate beyond tens of kHz. The presented method complements the existing technique with advantages of being flexible, high speed, and low cost. The 3D schlieren technique is first demonstrated and validated on the turbulent premixed flame and stable laminar premixed flame, respectively. Then, the 3D schlieren technique is used to measure the transient, dynamic ignition process. The results show that time-resolved 3D fundamental properties of ignition kernels (i.e., structure and edge speed) can be obtained by the technique.

Loss of ARHGAP40 expression in basal cell carcinoma via CpG island hypermethylation.

Basal cell carcinoma (BCC) is the most common malignant tumour arising from the basal cells of the epidermis or follicular structures. The aetiology of BCC is a multifactorial combination of genotype, phenotype and environmental factors. The pathogenesis of BCC remains unclear, with diverse and complex signalling pathways involved. ARHGAP40 is a Rho GTPase-activating protein (RhoGAP). Rho GTPases play a crucial role in the formation and progression of numerous cancers. The expression levels and roles of ARHGAP40 in BCC have not been explored. Here, ARHGAP40 expression was detected in a set of formalin-fixed, paraffin-embedded (FFPE) samples of basal cell carcinoma, paracancerous normal skin and benign skin lesions. The epigenetic mechanism that downregulates ARHGAP40 in basal cell carcinoma was investigated. We found that ARHGAP40 is expressed in normal basal cells and most benign skin lesions but lost in most basal cell carcinomas. We detected CpG island hypermethylation at the promoter-associated region of ARHGAP40. Our data suggest that ARHGAP40 is downregulated in BCC due to hypermethylation. ARHGAP40 protein is a potential novel biomarker for distinguishing trichoblastoma from BCC. This report is preliminary, and extensive research into the role of ARHGAP40 in BCC carcinogenesis and its potential as a treatment target is required in the future.

Effects of intermittently scanned continuous glucose monitoring in adult type 1 diabetes patients with suboptimal glycaemic control: A multi-centre randomized controlled trial.

AIMS: To investigate whether intermittently scanned continuous glucose monitoring without alarms (intermittently scanned CGM (isCGM)) improves glycaemic control over capillary blood glucose monitoring (BGM) among adult type 1 diabetes mellitus (T1DM) patients with suboptimal control. MATERIALS AND METHODS: Adults with T1DM and HbA1c between 7% and 10% were 1:1 randomized to use isCGM or BGM for 24 weeks. The primary outcome was the change in HbA1c levels after intervention. The secondary outcomes were the changes in sensor-derived metrics. RESULTS: A total of 104 adults with T1DM (34.2 ± 12.2 years; M/F, 38/66) were randomized to the isCGM group (n = 54) and the BGM group (n = 50). After 24 weeks, HbA1c significantly decreased in the isCGM group (8.1 ± 0.7% to 7.5 ± 1.0%) and the BGM group (8.0 ± 0.8% to 7.7 ± 1.0%) with between-group differences of 0.3% (95% coefficient intervals, 0.0%-0.6%; P = 0.04). The percentage of HbA1c reduction over 1.0% and 1.5% was significantly higher in the isCGM group with adjusted odds ratios of 2.5 (95% CI: 1.1-5.5; P = 0.03) and 3.2 (95% CI: 1.1-9.0; P = 0.03). Mean time-in-range 70-180 mg/dl (TIR) in the isCGM group significantly increased (from 58.5 ± 13.0% to 63.0 ± 12.6%), whereas mean TIR was similar in the BGM group (from 58.0 ± 14.6% to 57.5 ± 14.5%). Time spent in hyperglycemia reduced more in the isCGM group and time spent in hypoglycemia did not change significantly in both groups. CONCLUSIONS: Among adult T1DM patients with suboptimal glycaemic control, compared with BGM, isCGM use resulted in a statistically significant improvement in glycaemic control after 24-week intervention. TRIAL REGISTRATION: Clinicaltrials.gov Identifier (NCT03522870).

Association between Serum 25-Hydroxyvitamin D Concentrations and Respiratory Infection among United States Adults.

BACKGROUND: Vitamin D plays an essential role in immune responses to infections. However, the association between serum 25(OH)D concentrations and respiratory infection remains unclear. OBJECTIVES: The current study aimed to examine the association between serum 25(OH)D concentrations and respiratory infection among the United States adults. METHODS: This cross-sectional study used data from the NHANES 2001-2014. Serum 25(OH)D concentrations were measured by radioimmunoassay or liquid chromatography-tandem mass spectrometry and were classified as ≥75.0 nmol/L (sufficiency), 50.0-74.9 nmol/L (insufficiency), 30.0-49.9 nmol/L (moderate deficiency), and <30 nmol/L (severe deficiency). The respiratory infections included self-reported head or chest cold as well as influenza, pneumonia, or ear infection within the last 30 d. The associations between serum 25(OH)D concentrations and respiratory infections were examined using weighted logistic regression models. Data are presented as ORs and 95% CIs. RESULTS: This study included 31,466 United States adults ≥20 y of age (47.1 y, 55.5% women) with a mean serum 25(OH)D concentration of 66.2 nmol/L. After adjusting for sociodemographic characteristics, season of examination, lifestyle and dietary factors, and body mass index, compared with participants with a serum 25(OH)D concentration ≥75.0 nmol/L, those with a serum 25(OH)D concentration <30 nmol/L had higher risk of head or chest cold (OR: 1.17; 95% CI: 1.01, 1.36) and other respiratory diseases, including influenza, pneumonia, and ear infections (OR: 1.84; 95% CI: 1.35, 2.51). In the stratification analyses, lower serum 25(OH)D concentrations were associated with a higher risk of head or chest cold in obese adults but not in nonobese adults. CONCLUSIONS: Serum 25(OH)D concentrations are inversely associated with respiratory infection occurrence among United States adults. This finding may shed light on the protective effect of vitamin D on the respiratory health.

Correlation of balance posturographic parameters during quiet standing with the berg balance scale in patients with parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is often clinically associated with posture instability and more easily falling. The Berg balance scale is a clinical indicator commonly used to subjectively evaluate a patient's balance ability. Meanwhile, computerized force platforms have been used in research on postural control. The various parameters obtained from posturography are interpreted to assess balance ability. The present study aims to explore the correlations between posturographic variables and the BBS, and furthermore to efficiently evaluate postural instability and fall risk of early and moderate PD patients. METHODS: A total of 46 PD patients were involved in the experiment. Patients were asked to perform BBS tests and force platform tests under eye open (EO) and eye closed (EC) conditions. The recorded COP signal was analyzed with the time domain statistical method, the frequency domain method of Power Spectral Density (PSD), and structural methods of Stabilogram Diffusion Analysis (SDA), Sway Density Plot (SDP) to retrieve different posturographic variables. The correlation between posturographic variables under EO and EC conditions with BBS was compared statistically. The significantly correlated posturographic parameters were then applied to analyze posturographic differences between different groups: faller vs. non-faller (patients with/without a history of falls in the past 12 months). RESULTS: Among the different posturographic parameters, the prediction ellipse area, the slope of the regression line at a high-frequency band of PSD in the medial-lateral (ML) direction, the crossover point of the regression lines of SDA in the anterior-posterior (AP) direction, and the distance between successive peaks of SDP had significant correlations with BBS. These selected BBS-related parameters also showed significant differences between faller and non-faller. The selected posturographic parameters can be used as effective indicators to evaluate the balance ability of Parkinson's disease patients.