A functional spectrum of PROKR2 mutations identified in isolated hypogonadotropic hypogonadism.

Isolated hypogonadotropic hypogonadism (IHH) is a rare disease with hypogonadism and infertility caused by the defects in embryonic migration of hypothalamic gonadotropin-releasing hormone (GnRH) neurons, hypothalamic GnRH secretion or GnRH signal transduction. PROKR2 gene, encoding a G-protein coupled receptor PROKR2, is one of the most frequently mutated genes identified in IHH patients. However, the functional consequences of several PROKR2 mutants remain elusive. In this study, we systematically analyzed the Gαq, Gαs and ERK1/2 signaling of 23 IHH-associated PROKR2 mutations which are yet to be functionally characterized. We demonstrate that blockage of Gαq, instead of MAPK/ERK pathway, inhibited PROK2-induced migration of PROKR2-expressing cells, implying that PROKR2-related IHH results primarily due to Gαq signaling pathway disruption. Combined with previous reports, we categorized a total of 63 IHH-associated PROKR2 mutations into four distinct groups according Gαq pathway functionality: (i) neutral (N, >80% activity); (ii) low pathogenicity (L, 50-80% activity); (iii) medium pathogenicity (M, 20-50% activity) and (iv) high pathogenicity (H, <20% activity). We further compared the cell-based functional results with in silico mutational prediction programs. Our results indicated that while Sorting Intolerant from Tolerant predictions were accurate for transmembrane region mutations, mutations localized in the intracellular and extracellular domains were accurately predicted by the Combined Annotation Dependent Depletion prediction tool. Our results thus provide a functional database that can be used to guide diagnosis and appropriate genetic counseling in IHH patients with PROKR2 mutations.

Venetoclax plus a hypomethylating agent versus cytarabine, aclarubicin, and granulocyte colony-stimulating factor chemotherapy as a first-line therapy for newly diagnosed acute myeloid leukemia: A propensity score-matched analysis.

BACKGROUND: Both venetoclax plus a hypomethylating agent (VEN/HMA) and cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CAG) are low-intensity regimens for older patients with acute myeloid leukemia (AML) that show good efficacy and safety. It is unknown how VEN/HMA compares with the CAG regimen for the treatment of newly diagnosed AML. METHODS: The outcomes of patients with newly diagnosed AML treated with VEN/HMA were compared with those of patients treated with a CAG-based regimen. Propensity score matching between these two cohorts at a 1:1 ratio was performed according to age at diagnosis, sex, Eastern Cooperative Oncology Group performance status, state of fitness, and European LeukemiaNet (ELN) 2022 risk stratification to minimize bias. RESULTS: A total of 84 of 96 patients in the VEN/HMA cohort were matched with 84 of 147 patients in the CAG cohort. VEN/HMA resulted in a better response than the CAG-based regimens, as indicated by a higher composite complete remission (CRc) rate (82.1% vs. 60.7%; p = .002) and minimal residual disease negativity rate (88.2% vs. 68.2%; p = .009). In patients with an ELN adverse risk, VEN/HMA was associated with a higher CRc rate compared to CAG (80.5% vs. 58.3%; p = .006). VEN/HMA was associated with longer event-free survival (EFS) (median EFS, not reached vs. 4.5 months; p = .0004), whereas overall survival (OS) was comparable between the two cohorts (median OS, not reached vs. 18 months; p = .078). CONCLUSIONS: The VEN/HMA regimen may result in a better response than CAG-based treatment in older patients with newly diagnosed AML.

Ultrasensitive Dual-Mode Visual/Photoelectrochemical Bioassay for Antibiotic Resistance Genes through Incorporating Rolling Circle Amplicons into a Tailored Nanoassembly.

As emerging contaminants in the environment, antibiotic resistance genes (ARGs) have aroused a global health crisis and posed a serious threat to ecological safety and human health. Thus, efficient and accurate onsite detection of ARGs is crucial for environmental surveillance. Here, we presented a colorimetric-photoelectrochemical (PEC) dual-mode bioassay for simultaneous detection of multiple ARGs by smartly incorporating rolling circle amplification (RCA) into a stimuli-responsive DNA nanoassembly, using the tetracycline resistance genes tetA and tetC as models. The tailored DNA nanoassembly containing RCA amplicons hybridized with specific signal probes: CuO nanoflowers-anchored signal DNA1 and HgO nanoparticles-anchored signal DNA2, respectively. Upon exposure to an acidic stimulus, numerous Cu2+ and Hg2+ were released, serving as the reporting agent of colorimetric/PEC dual-mode assay. The released Cu2+ and Hg2+ induced localized surface plasmon resonance shifts in Au nanorods and triangular Ag nanoplates through an etching process, respectively, enabling visual analysis of ARGs with distinguishing color changes. Meanwhile, numerous Cu2+ and Hg2+ triggered the amplified PEC variations via reacting with the photoactive layers of CuS/CdS and ZnS, respectively. Thus, a rapid and ultrasensitive colorimetric/PEC dual-mode detection of multiple ARGs was achieved with the detection limit down to 17.2 aM. Furthermore, such dual-mode bioassay could discriminate single-base mismatch and successfully determine ARGs in E. coli plasmids and sludge samples, holding great promise for point-of-care genetic diagnostics.

USF2 promotes autophagy and proliferation in chronic lymphocytic leukemia by inhibiting STUB1-induced NFAT5 ubiquitination.

Chronic lymphocytic leukemia (CLL) mainly affects the health of older adults and is difficult to cure. Upstream stimulatory factor 2 (USF2) has been implicated in several diseases and conditions including cancers. However, the effect of USF2 on CLL has not been elucidated. To investigate the effect of USP2 on proliferation and autophagy of CLL, and to explore the underlying mechanism. The mRNA of USF2 and STIP1 homology and U-Box containing protein 1 (STUB1) was analyzed using qRT-PCR. Western blots were used to evaluate the expression level of USF2, LC3II, Beclin-1, P62, STUB1, and NFAT5. The cell proliferation was evaluated using CCK-8 and EdU assays. The cell apoptosis was evaluated using flow cytometry. Indirect fluorescent assay (IFA) was performed to analyze LC3 signal. Nuclear factor of activated T-cells 5 (NFAT5) ubiquitination was detected using immunoprecipitation (IP) assay. The CLL progression was evaluated in xenotransplantation model of nude mice. USF2 was highly expressed in CLL tissues and cell lines. USF2 knockdown suppressed the cell viability and EdU incorporation, while promoting cell apoptosis. Meanwhile, USF2 knockdown reduced the level of LC3II and Beclin-1, but increased P62, illustrating USF2 knockdown inhibiting autophagy. USF2 induced NFAT5 ubiquitination and promoted NFAT5 protein level via repressing STUB1. The downregulation of USF2 weakened CLL progression in xenotransplantation model of nude mice. CLL survival and autophagy was dependent on highly expressed USF2 which promoted the expression and ubiquitination of NFAT5 through inhibiting the transcription of STUB1, which makes USF2 a promising therapeutic candidate for CLL treatment.

Fetal overgrowth and weight trajectories during infancy and adiposity in early childhood.

BACKGROUND: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood. Little is known about how infancy growth trajectories affect adiposity in early childhood in LGA. METHODS: In the Shanghai Birth Cohort, we followed up 259 LGA (birth weight >90th percentile) and 1673 appropriate-for-gestational age (AGA, 10th-90th percentiles) children on body composition (by InBody 770) at age 4 years. Adiposity outcomes include body fat mass (BFM), percent body fat (PBF), body mass index (BMI), overweight/obesity, and high adiposity (PBF >85th percentile). RESULTS: Three weight growth trajectories (low, mid, and high) during infancy (0-2 years) were identified in AGA and LGA subjects separately. BFM, PBF and BMI were progressively higher from low- to mid-to high-growth trajectories in both AGA and LGA children. Compared to the mid-growth trajectory, the high-growth trajectory was associated with greater increases in BFM and the odds of overweight/obesity or high adiposity in LGA than in AGA children (tests for interactions, all P < 0.05). CONCLUSIONS: Weight trajectories during infancy affect adiposity in early childhood regardless of LGA or not. The study is the first to demonstrate that high-growth weight trajectory during infancy has a greater impact on adiposity in early childhood in LGA than in AGA subjects. IMPACT: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood, but little is known about how weight trajectories during infancy affect adiposity during early childhood in LGA subjects. The study is the first to demonstrate a greater impact of high-growth weight trajectory during infancy (0-2 years) on adiposity in early childhood (at age 4 years) in subjects with fetal overgrowth (LGA) than in those with normal birth size (appropriate-for-gestational age). Weight trajectory monitoring may be a valuable tool in identifying high-risk LGA children for close follow-ups and interventions to decrease the risk of obesity.

Association of serum soluble α­klotho with risk of kidney stone disease: a population-based cross-sectional study.

BACKGROUND: The aim of the study was to explore the association of serum soluble klotho with kidney stone disease (KSD) in the general population over the age of 40 years in the United States. METHODS: We integrated the data in National Health and Nutrition Examination Survey from 2007 to 2016 years. The relationship between serum soluble α­klotho and prevalence of KSD was analyzed by constructing weighted multivariable logistic regression model, restricted cubic spline (RCS) curve, and subgroup analyses. RESULTS: In the study, a total of 13,722 individuals were included in our study. A U-shaped association between serum soluble klotho and the risk of KSD was shown by the RCS curve (P value for nonlinear < 0.05). In the full adjusted model, compared with the lowest quartile of serum soluble α­klotho, the adjusted odd ratios (95% confidence intervals) for KSD across the quartiles were (0.999 (0.859, 1.164), 1.005 (0.858, 1.176), and 1.061 (0.911, 1.235)). Subgroup analyses also showed that the U-shaped association of serum soluble α­klotho with KSD was found among subjects who were age < 60 years, female or male, with or without hypertension, and BMI ≥ 30 kg/m2. CONCLUSIONS: Our findings suggested that serum klotho levels had a U-shaped correlation with risk of KSD. When the Klotho level is at 818.66 pg/mL, prevalence of KSD is lowest. Therefore, maintaining a certain level of serum soluble α­klotho could prevent the occurrence of KSD.

Global burden of young-onset gastric cancer: a systematic trend analysis of the global burden of disease study 2019.

BACKGROUND: While gastric cancer is generally declining globally, the temporal trend of young-onset (< 40 years) gastric cancer remains uncertain. We performed this analysis to determine the temporal trends of young-onset gastric cancer compared to late-onset cancer (≥ 40 years). METHODS: We extracted cross-sectional data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The burden of gastric cancer from 1990 to 2019 was assessed through indicators including incidence and mortality rates, which were classified at global, national, and regional levels, and according to socio-demographic indexes (SDI) and age or sex groups. Joinpoint regression analysis was used to identify specific years with significant changes. The correlation between AAPC with countries' average SDI was tested by Pearson's Test. RESULTS: The global incidence rate of young-onset gastric cancer decreased from 2.20 (per 100,000) in 1990 to 1.65 in 2019 (AAPC: - 0.95; 95% confidence interval [CI] - 1.25 to - 0.65; P < 0.001). Late-onset cancer incidence also decreased from 59.53 (per 100,000) in 1990 to 41.26 in 2019 (AAPC: - 1.23; 95% CI - 1.39 to - 1.06, P < 0.001). Despite an overall decreasing trend, the incidence rate of young-onset cancer demonstrated a significant increase from 2015 to 2019 (annual percentage change [APC]: 1.39; 95% CI 0.06 to 2.74; P = 0.041), whereas no upward trend was observed in late-onset cancer. Mortality rates of young- and late-onset cancer both exhibited a significant decline during this period (AAPC: - 1.82; 95% CI - 2.15 to - 1.56; P < 0.001 and AAPC: - 1.69, 95% CI - 1.79 to - 1.59; P < 0.001). The male-to-female rate ratio for incidence and mortality in both age groups have been increasing since 1990. While countries with high SDI have had a greater decline in the incidence of late-onset gastric cancer (slope of AAPC change: - 0.20, P = 0.004), it was not observed in young-onset cancer (slope of AAPC change: - 0.11, P = 0.13). CONCLUSIONS: The global incidence and mortality rates of both young- and late-onset gastric cancer have decreased since 1990. However, the incidence rate of young-onset cancer has demonstrated a small but significant upward trend since 2015. There was disparity in the decline in young-onset gastric cancer among male and high SDI countries. These findings could help to inform future strategies in preventing gastric cancer in younger individuals.

The benefit of omeprazole exposure on all-cause mortality and length of ICU/hospital stay might vary with age in critically ill pediatric patients: A cohort study.

PURPOSE: To investigate the association between proton pump inhibitors (PPIs) administration during hospitalization and mortality and length of stay in critically ill pediatric patients. MATERIALS AND METHODS: This is a retrospective observational cohort study on pediatric ICU patients (0 to 18 years). Propensity score matching (PSM), Kaplan-Meier curves, Cox proportional hazards model and Linear regression model was applied for assessing the effects of PPIs on mortality and other outcomes during hospitalization. RESULTS: A total of 2269 pediatric ICU patients were included, involving 1378 omeprazole (OME) users and 891 non-OME users. The results showed significant association between OME exposure and decreased ICU stay (ß -0.042; 95% CI -0.073--0.011; P = 0.008) but prolonged non-ICU hospital stay (ß 0.121; 95% CI 0.097-0.155; P = 0.040). No statistical significance was observed between OME exposure and reduced mortality, but the OME group had a slightly decreased tendency in 28-day mortality (HR 0.701; 95% CI 0.418-1.176) and in-hospital mortality (HR 0.726; 95% CI 0.419-1.257). Furthermore, subgroup analyses revealed that the decreased tendency of mortality were more obvious in patients less than 1 year old compared with older pediatric patients, although not statistically significant. In addition, we also observed that OME exposure was significantly associated with reduced mortality of general ICU subgroup. CONCLUSIONS: This study provided a sign that PPIs used only in the ICU, rather than throughout hospital stay, might provide more benefit for critically ill pediatric patients. Additionally, younger pediatric patients might gain relatively more benefit than older children when receiving PPIs.

Glutamic-acid grafted hyaluronic acid inhibits inflammatory factors via fibroblast and skin model tests.

BACKGROUND: Excessive inflammation may cause tissue damage and disrupt the function of the skin barrier. Hyaluronic acid (HA), an endogenous component, was found to regulate multiple inflammatory factors for skin health. This work aims to further enhance its efficacy by grafting amino acid onto its molecule. METHODS: Glutamic acid (Glu) was selected as the ligand to react with low-molecular-weight HA. Fibroblast tests and a 3D skin model were used to investigate the anti-inflammation efficacy of HA-Glu. RESULTS: For IL-1α, IL-6 and TNF-α, the grafted compound presents stronger inhibition ability versus native HA. Moreover, HA-Glu could promote the repair of damaged skin by improving the compactness of the stratum corneum and increasing the thickness of the living cell layer. CONCLUSION: The application of HA-Glu compound in skin care formulas would be effective to alleviate inflammation-induced skin symptoms and skin aging.

A meta-analysis of associations of IL-10 gene polymorphisms with acute leukemia susceptibility.

BACKGROUND: Recently, increasing evidence has demonstrated that IL-10 single nucleotide polymorphisms (SNPs) are associated with the risk of acute leukemia (AL), but the findings of different articles remain controversial. Thus, we performed a meta-analysis to further investigate the exact roles of IL-10 SNPs in AL susceptibility. METHODS: Six common Chinese and English databases were utilized to retrieve eligible studies. The strength of the association was assessed by calculating odds ratios and 95 % confidence intervals. All analyses were carried out using Review Manager (version 5.3) and STATA (version 15.1). The registered number of this research is CRD42022373362. RESULTS: A total of 6391 participants were enrolled in this research. The results showed that the AG genotype of rs1800896 increased AL risk in the heterozygous codominant model (AG vs. AA, OR = 1.41, 95 % CI = 1.04-1.92, P = 0.03) and overdominant model (AG vs. AA + GG, OR = 1.32, 95 % CI = 1.04-1.70, P = 0.03). In the subgroup analysis, associations between the G allele, GG genotype, AG genotype, AG + GG genotype of rs1800896 and increased AL risk were also observed in the mixed population based on allelic, homozygote codominant, heterozygous codominant, dominant, and overdominant models. Furthermore, an association between the AC genotype of rs1800872 and increased AL risk was observed in the Caucasian population in the overdominant model. However, the rs1800871, rs3024489 and rs3024493 polymorphisms did not affect AL risk. CONCLUSION: IL-10 rs1800896 and rs1800872 affected the susceptibility of AL and therefore may be biomarkers for early screening and risk prediction of AL.

Comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for low-risk gestational trophoblastic neoplasia (FIGO Score 0-4): study protocol for a prospective, multicentre, randomized trial.

BACKGROUND: Single-agent chemotherapy using methotrexate or actinomycin D is the first-line treatment for patients with low-risk gestational trophoblastic neoplasia. Various methotrexate-based and actinomycin D-based single-agent regimens can be used. However, there is insufficient evidence to determine the superior regimen. To guide doctors in selecting a single-agent chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia, we will compare two regimens. METHODS: We will conduct a multicentre, randomized, prospective clinical trial. Selected low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4) will be randomized 1:1 to a biweekly single-dose actinomycin D group or a multiday methotrexate therapy group. The actinomycin D group will receive IV pulse actinomycin D (1.25 mg/m2) every 14 days, and the methotrexate group will receive methotrexate (50 mg) intramuscularly on days 1, 3, 5, and 7 (4 doses per cycle) and leucovorin (15 mg) intramuscularly on days 2, 4, 6, and 8. This process will be repeated every 14 days. The primary endpoints will include the complete remission rate by single-agent therapy and the overall complete remission rate. The secondary endpoints will include the duration needed to achieve complete remission after single-agent chemotherapy, number of courses needed to achieve complete remission after single-agent chemotherapy, incidence and severity of adverse effects, effects on menstrual conditions and ovarian function based on the anti-Mullerian hormone level, and patient-reported quality of life. DISCUSSION: Previous clinical trials comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for treating low-risk gestational trophoblastic neoplasia patients failed to meet the expected case number. Through this multicentre study, the complete remission ratio and efficacy difference between biweekly single-dose actinomycin D and multiday methotrexate therapy will be obtained. This study will also provide the basis for formulating a preferred regimen for treating patients with low-risk gestational trophoblastic neoplasia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04562558, Registered on 13 September 2020 (Protocol version 2020-9-24, version 1.0).

Steatotic hepatocyte-derived extracellular vesicles promote ß-cell apoptosis and diabetes via microRNA-126a-3p.

Extracellular vesicles (EVs) have emerged as a unique mediator of interorgan communications, playing important roles in the pathophysiologic process of various diseases, including diabetes and other metabolic diseases. Here, we reported that the EVs released by steatotic hepatocytes exerted a detrimental effect on pancreatic ß cells, leading to ß-cell apoptosis and dysfunction. The effect was profoundly attributable to an up-regulation of miR-126a-3p in the steatotic hepatocyte-derived EVs. Accordingly, overexpression of miR-126a-3p promoted, whereas inhibition of miR-126a-3p prevented ß-cell apoptosis, through a mechanism related to its target gene, insulin receptor substrate-2. Moreover, inhibition of miR-126a-3p by its specific antagomir was able to partially reverse the loss of ß-cell mass and ameliorate hyperglycaemia in diabetic mice. Thus, the findings reveal a novel pathogenic role of steatotic hepatocyte-derived EVs, which mechanistically links nonalcoholic fatty liver disease to the development of diabetes.

Risk of hospitalization for upper gastrointestinal bleeding in Helicobacter pylori eradicated patients newly started on warfarin or direct oral anticoagulants: A population-based cohort study.

BACKGROUND: To investigate risks of hospitalization for upper gastrointestinal bleeding (UGIB) in H. pylori-eradicated patients newly started on warfarin or direct oral anti-coagulants (DOACs). METHODS: We identified all patients who had previously received H. pylori eradication therapy or were found to have no H. pylori on endoscopy and were then newly started on warfarin or DOACs from a population-based electronic healthcare database. Primary analysis was the risk of UGIB between warfarin and DOACs users in H. pylori-eradicated patients. Secondary analysis included the UGIB risk between H. pylori-eradicated and H. pylori-negative patients who were newly started on warfarin or DOACs. The hazard ratio (HR) of UGIB was approximated by pooled logistic regression model incorporating the inverse propensity of treatment weightings with time-varying covariables. RESULTS: Among H. pylori-eradicated patients, DOACs had a significantly lower risk of UGIB (HR: 0.26, 95% CI 0.09-0.71) compared with warfarin. In particular, lower UGIB risks with DOACs were observed among older (≥65 years) patients, female, those without a history of UGIB or peptic ulcer, or ischemic heart disease, and non-users of acid-suppressive agents or aspirin. Secondary analysis showed no significant difference in UGIB risk between H. pylori-eradicated and H. pylori-negative patients newly started on warfarin (HR: 0.63,95% CI 0.33-1.19) or DOACs (HR: 1.37, 95% CI 0.45-4.22). CONCLUSIONS: In H. pylori-eradicated patients, new users of DOACs had a significantly lower risk of UGIB than new warfarin users. Furthermore, the risk of UGIB in new warfarin or DOACs users was comparable between H. pylori-eradicated and H. pylori-negative patients.

Automatic, Early Color-Specific Neural Responses to Object Color Knowledge.

Some familiar objects are associated with specific colors, e.g., rubber ducks with yellow. Whether and at what stage neural responses occur to these color associations remain open questions. We recorded frequency-tagged electroencephalogram (EEG) responses to periodic presentations of yellow-associated objects, shown among sequences of non-periodic blue-, red-, and green-associated objects. Both color and grayscale versions of the objects elicited yellow-specific responses, indicating an automatic activation of color knowledge from object shape. Follow-up experiments replicated these effects with green-specific responses, and demonstrated modulated responses for incongruent color/object associations. Importantly, the onset of color-specific responses was as early to grayscale as actually colored stimuli (before 100 ms), the latter additionally eliciting a conventional later response (approximately 140-230 ms) to actual stimulus color. This suggests that the neural representation of familiar objects includes both diagnostic shape and color properties, such that shape can elicit associated color-specific responses before actual color-specific responses occur.

Extended application of defective metal oxide BiO2-x: Liquid phase low-temperature thermal catalysis for the removal of phenolic pollutants.

Bismuth oxide (BiO2-x) with oxygen vacancies was created using a hydrothermal process and was found to exhibit good catalytic oxidation performance under low-temperature heating without the addition of external oxidants. The catalytic activity of BiO2-x was tested using 4-chlorophenol (4-CP) as the target aqueous pollutant. We observed that 10 ppm of 4-CP was completely degraded within 40 min at a reaction temperature of 65 °C. The effective elimination of 4-CP was attributed to active oxygen species produced by the release of lattice oxygen. Furthermore, the low-temperature thermal catalytic activity of BiO2-x was affected by the electron transfer characteristics of pollutants, leading to the rapid degradation of electron-rich pollutants. This study reveals the unique application of BiO2-x as a catalyst for removing phenolic pollutants under low-temperature thermal catalysis, thereby expanding its catalytic application scenarios and offering a new approach for the degradation of phenolic pollutants.

Sensorimotor synchronization with visual, auditory, and tactile modalities.

While it is well known that humans are highly responsive to rhythm, the factors that influence our ability to synchronize remain unclear. In the current study, we examined how stimulus modality and rhythmic deviation, along with the synchronizer's level of musicality, impacted sensorimotor synchronization (SMS). Utilizing a finger-tapping task and three sensory modalities (visual, auditory, and tactile), we manipulated rhythmic deviation by varying the temporal position, intensity, and availability of cues across four deviation levels. Additionally, to determine our participants' musical familiarity and aptitude, we administered the Goldsmiths Musical Sophistication Index (Gold-MSI) questionnaire. We found that SMS to external rhythmic stimuli was significantly more precise for auditory and tactile than for visual sequences. Further, we found SMS consistency significantly decreased in all modalities with increased rhythmic deviation, suggesting rhythmic deviation directly relates to SMS difficulty. Moreover, a significant correlation was found between Gold-MSI scores and SMS consistency in the most rhythmically deviant level, such that the higher one's musical general sophistication score, the greater one's SMS ability. This held for all three modalities. Combined, these findings suggest that rhythmic synchronization performance is affected not only by the modality and rhythmic deviation of the stimuli but also by the musical general sophistication of the synchronizer.

Improved membrane stability of alginate-chitosan microcapsules by crosslinking with tannic acid.

OBJECTIVE: The insufficient stability of alginate-chitosan (ALG-CS) microcapsules in biorelevant media limits their applications in the biomedical field. Attempts were made to improve the membrane stability of ALG-CS microcapsules by noncovalent crosslinking with tannic acid. RESULTS: The membrane stability of ALG-CS microcapsules in culture medium and serum was significantly improved by crosslinking with tannic acid. Moreover, the reason for the significant improvement in membrane stability had been demonstrated to be that the stability of chitosan-tannic acid (CS-TA) polyelectrolyte complexes was less affected by the competitive binding of those weak acid ions such as HCO3-. In addition, the optimal conditions for preparing alginate-chitosan-tannic acid (ALG-CS-TA) microcapsules were tannic acid concentration of 0.5% (w/v) and pH = 7. CONCLUSION: The study provides a novel approach for improving the stability of the ALG-CS microcapsules in biorelevant media to expand their scope of application in the biological field.

JUTAR: Joint User-Association, Task-Partition, and Resource-Allocation Algorithm for MEC Networks.

Mobile edge computing (MEC) is a promising technique to support the emerging delay-sensitive and compute-intensive applications for user equipment (UE) by means of computation offloading. However, designing a computation offloading algorithm for the MEC network to meet the restrictive requirements towards system latency and energy consumption remains challenging. In this paper, we propose a joint user-association, task-partition, and resource-allocation (JUTAR) algorithm to solve the computation offloading problem. In particular, we first build an optimization function for the computation offloading problem. Then, we utilize the user association and smooth approximation to simplify the objective function. Finally, we employ the particle swarm algorithm (PSA) to find the optimal solution. The proposed JUTAR algorithm achieves a better system performance compared with the state-of-the-art (SOA) computation offloading algorithm due to the joint optimization of the user association, task partition, and resource allocation for computation offloading. Numerical results show that, compared with the SOA algorithm, the proposed JUTAR achieves about 21% system performance gain in the MEC network with 100 pieces of UE.

Distribution of Bioelectrical Impedance Vector Analysis and Phase Angle in Korean Elderly and Sarcopenia.

PURPOSE: This study aimed to verify whether bioelectrical impedance vector analysis (BIVA) can support the clinical evaluation of sarcopenia in elderly individuals and evaluate the relationships between phase angle (PhA), physical performance, and muscle mass. METHODS: The sample comprised 134 free-living elderly individuals of both sexes aged 69-91 years. Anthropometric parameters, grip strength, dual-energy X-ray absorptiometry findings, bioimpedance analysis results, and physical performance were also measured. The impedance vector distributions were evaluated in elderly individuals using BIVA. RESULTS: BIVA revealed significant differences between the sarcopenia and non-sarcopenia groups (both sexes). The sarcopenia group had a significantly lower PhA than the non-sarcopenia group in both sexes (p < 0.05). PhA was significantly correlated with age, appendicular skeletal muscle (ASM), handgrip strength (HGS), and muscle quality in both sexes and significantly correlated with ASM/Height2 and physical performance in males. CONCLUSION: BIVA can be used as a field assessment method in elderly Koreans with sarcopenia. PhA is a good indicator of muscle strength, muscle quality, and physical performance in males. These methods can help diagnose sarcopenia in elderly individuals with reduced mobility.

Immunologic Signatures across Molecular Subtypes and Potential Biomarkers for Sub-Stratification in Endometrial Cancer.

Current molecular classification approaches for endometrial cancer (EC) often employ multiple testing platforms. Some subtypes still lack univocal prognostic significance, highlighting the need for risk sub-stratification. The tumor immune microenvironment (TIME) is associated with tumor progression and prognosis. We sought to investigate the feasibility of classifying EC via DNA sequencing and interrogate immunologic signatures and prognostic markers across and within subtypes, respectively. Formalin-fixed paraffin-embedding (FFPE) samples from 50 EC patients underwent targeted DNA and RNA sequencing, and multiplex immunofluorescence assay for TIME. DNA sequencing classified 10%, 20%, 52%, and 18% of patients into the subtype of POLE-mutant, microsatellite instability-high (MSI-H), TP53-wt, and TP53-mutant. POLE-mutant tumors expressed the highest T-effector and IFN-γ signature and the lowest innate anti-PD-1 resistance signature among subtypes. TP53-wt revealed a converse enrichment trend for these immunologic signatures. Survival analyses using the Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) dataset identified associations of CCR5 (hazard ratio (HR) = 0.71, p = 0.035), TNFRSF14 (HR = 0.58, p = 0.028), and IL-10 (HR = 2.5, p = 0.012) with overall survival within MSI-H, TP53-mutant, and TP53-wt subtype, respectively. A TIME comparison between the sub-stratified subgroups of our cohort revealed upregulated tumor infiltration of immune cells in the low-risk subgroups. Our study demonstrates that targeted DNA sequencing is an effective one-stop strategy to classify EC. Immunomodulatory genes may serve as prognostic markers within subtypes.