Home Health Quality among Hospitalized Older Adults with Alzheimer's Disease and Related Dementia: Association with Race/Ethnicity and Dual Eligibility before and during the COVID Pandemic.

OBJECTIVES: During the COVID-19 pandemic, home health agencies (HHAs) discharges following acute hospitalizations increased. This study examined whether racial and ethnic minoritized and socioeconomically disadvantaged patients (ie, Medicare-Medicaid dual-eligible) were differentially discharged to below-average quality HHAs before and during the COVID-19 pandemic. We focused on post-acute patients with Alzheimer's disease and related dementias (ADRD), who are generally frail and have high care needs. DESIGN: Cohort study. SETTING AND PARTICIPANTS: We linked 2019 to 2021 Medicare data with Area Deprivation Index (ADI), Home Health Compare, and COVID-19 infection data. We included Medicare beneficiaries with ADRD who were hospitalized for non-COVID-19 conditions and discharged to HHAs between January 2019 and November 2021. The final analytical sample included 426,766 qualified hospitalization events. METHODS: The outcome variable was whether a patient received care from a below-average quality HHA, defined by an average Quality of Patient Care Star Rating lower than 3.0. Key independent variables included individual race, ethnicity, and Medicare-Medicaid dual status. Linear probability models with county fixed effects were estimated, sequentially adjusting for the individual- and community-level covariates. Sensitivity analysis using various definitions of below-average quality HHAs was conducted. RESULTS: Before the pandemic, Black and Hispanic individuals had significantly higher probabilities of discharge to below-average quality HHAs compared with white individuals (3.4 and 3.9 percentage points, respectively). Dual-eligible individuals were also 2.5 percentage points more likely to be discharged to below-average quality HHAs. During the pandemic, disparities in being discharged to below-average quality HHAs persisted among racial and ethnic minoritized patients and increased among duals. Findings were consistent with and without adjusting for individual covariates and across different definitions of below-average quality HHA. CONCLUSIONS AND IMPLICATIONS: Persistent disparities were observed in being discharged to below-average quality HHAs by race, ethnicity, and dual status. Further research is needed to identify factors contributing to these ongoing inequalities.

Alpha-Lipoic Acid Induces Adipose Tissue Browning through AMP-Activated Protein Kinase Signaling in Vivo and in Vitro.

Background: AMP-activated protein kinase (AMPK) is a key enzyme for cellular energy homeostasis and improves metabolic disorders. Brown and beige adipose tissues exert thermogenesis capacities to dissipate energy in the form of heat. Here, we investigated the beneficial effects of the antioxidant alpha-lipoic acid (ALA) in menopausal obesity and the underlying mechanisms. Methods: Female Wistar rats (8 weeks old) were subjected to bilateral ovariectomy (Ovx) and divided into four groups: Sham (n=8), Ovx (n=11), Ovx+ALA2 (n=10), and Ovx+ALA3 (n=6) (ALA 200 and 300 mg/kg/day, respectively; gavage) for 8 weeks. 3T3-L1 cells were used for in vitro study. Results: Rats receiving ALA2 and ALA3 treatment showed significantly lower levels of body weight and white adipose tissue (WAT) mass than those of the Ovx group. ALA improved plasma lipid profiles including triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Hematoxylin & eosin staining of inguinal WAT showed that ALA treatment reduced Ovx-induced adipocyte size and enhanced uncoupling protein 1 (UCP1) expression. Moreover, plasma levels of irisin were markedly increased in ALA-treated Ovx rats. Protein expression of brown fat-specific markers including UCP1, PRDM16, and CIDEA was downregulated by Ovx but markedly increased by ALA. Phosphorylation of AMPK, its downstream acetyl-CoA carboxylase, and its upstream LKB1 were all significantly increased by ALA treatment. In 3T3-L1 cells, administration of ALA (100 and 250 µM) reduced lipid accumulation and enhanced oxygen consumption and UCP1 protein expression, while inhibition of AMPK by dorsomorphin (5 µM) significantly reversed these effects. Conclusion: ALA improves estrogen deficiency-induced obesity via browning of WAT through AMPK signaling.

Advancing climate-resilient flood mitigation: Utilizing transformer-LSTM for water level forecasting at pumping stations.

Proactive management of pumping stations using artificial intelligence (AI) technology is vital for effectively mitigating the impacts of flood events caused by climate change. Accurate water level forecasts are pivotal in advancing the intelligent operation of pumping stations. This study proposed a novel Transformer-LSTM model to offer accurate multi-step-ahead forecasts of the flood storage pond (FSP) and river water levels for the Zhongshan pumping station in Taipei, Taiwan. A total of 19,647 ten-minute-based datasets of pumping operation and storm sewer, FSP, and river water levels were collected between 2014 and 2020 and further divided into training (70 %), validation (10 %), and test (20 %) datasets for model construction. The results demonstrate that the proposed model dramatically outperforms benchmark models by producing more accurate and reliable water level forecasts at 10-minute (T + 1) to 60-minute (T + 6) horizons. The proposed model effectively enhances the connections between input factors through the Transformer module and increases the connectivity across consecutive time series using the LSTM module. This study reveals interconnected dynamics among pumping operation and storm sewer, FSP, and river water levels, enhancing flood management. Understanding these dynamics is crucial for effective execution of management strategies and infrastructure revitalization against climate impacts. The Transformer-LSTM model's forecasts encourage water practices, resilience, and disaster risk reduction for extreme weather events.

Virtual MOLLI Target: Generative Adversarial Networks Toward Improved Motion Correction in MRI Myocardial T1 Mapping.

BACKGROUND: The modified Look-Locker inversion recovery (MOLLI) sequence is commonly used for myocardial T1 mapping. However, it acquires images with different inversion times, which causes difficulty in motion correction for respiratory-induced misregistration to a given target image. HYPOTHESIS: Using a generative adversarial network (GAN) to produce virtual MOLLI images with consistent heart positions can reduce respiratory-induced misregistration of MOLLI datasets. STUDY TYPE: Retrospective. POPULATION: 1071 MOLLI datasets from 392 human participants. FIELD STRENGTH/SEQUENCE: Modified Look-Locker inversion recovery sequence at 3 T. ASSESSMENT: A GAN model with a single inversion time image as input was trained to generate virtual MOLLI target (VMT) images at different inversion times which were subsequently used in an image registration algorithm. Four VMT models were investigated and the best performing model compared with the standard vendor-provided motion correction (MOCO) technique. STATISTICAL TESTS: The effectiveness of the motion correction technique was assessed using the fitting quality index (FQI), mutual information (MI), and Dice coefficients of motion-corrected images, plus subjective quality evaluation of T1 maps by three independent readers using Likert score. Wilcoxon signed-rank test with Bonferroni correction for multiple comparison. Significance levels were defined as P < 0.01 for highly significant differences and P < 0.05 for significant differences. RESULTS: The best performing VMT model with iterative registration demonstrated significantly better performance (FQI 0.88 ± 0.03, MI 1.78 ± 0.20, Dice 0.84 ± 0.23, quality score 2.26 ± 0.95) compared to other approaches, including the vendor-provided MOCO method (FQI 0.86 ± 0.04, MI 1.69 ± 0.25, Dice 0.80 ± 0.27, quality score 2.16 ± 1.01). DATA CONCLUSION: Our GAN model generating VMT images improved motion correction, which may assist reliable T1 mapping in the presence of respiratory motion. Its robust performance, even with considerable respiratory-induced heart displacements, may be beneficial for patients with difficulties in breath-holding. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Preclinical systolic dysfunction relating to ankle-brachial index among high-risk PAD population with preserved left ventricular ejection fraction.

Peripheral artery disease (PAD) shares common clinical risk factors, for example, endothelial dysfunction, with preserved ejection fraction (LVEF) heart failure (HFpEF). Whether PAD is associated with preclinical systolic dysfunction and higher HF risk among individuals presenting preserved LVEF remains uncertain. We retrospectively included outpatients with at least one known or established cardiovascular (CV) risk factor with LVEF ≥ 50%. Patients were categorized into high risk and low risk of developing PAD (PAD vs Non-PAD) by ankle-brachial index (ABI) (≤ 0.90 or > 1.4) and further stratified based on their history of HFpEF (HFpEF vs. Non-HFpEF), resulting in the formation of four distinct strata. Preclinical systolic dysfunction was defined using dedicated speckle-tracking algorithm. A total of 2130 consecutive patients were enrolled in the study, with a median follow-up of 4.4 years. The analysis revealed a higher prevalence of high risk of developing PAD in patients with HFpEF compared to those without HFpEF (25.1% vs. 9.4%). Both high risk of developing PAD and HFpEF were independently associated with preclinical systolic dysfunction (global longitudinal strain, GLS ≥ - 18%) (odds ratio, OR: 1.38; 95% confidence interval, CI: 1.03-1.86). In comparison to patients at low risk of developing PAD without HFpEF (Non-PAD/Non-HFpEF group), those categorized as having a high risk of developing PAD with HFpEF (PAD/HFpEF group) exhibited the most impaired GLS and a heightened susceptibility to heart failure hospitalization (hazard ratio, HR: 6.51; 95% CI: 4.43-9.55), a twofold increased risk of all-cause mortality (HR: 2.01; 95% CI: 1.17-3.38), cardiovascular mortality (HR: 2.44; 95% CI: 1.08-5.51), and non-cardiovascular mortality (HR: 1.78; 95% CI: 0.82-3.84). A high risk of developing PAD was strongly linked to impaired preclinical systolic function and an increased likelihood for subsequent hospitalization for HF, all-cause mortality, CV mortality and non-CV mortality. There is a clear need for preventive strategies aimed at reducing hospitalizations for HF and mortality in this high-risk population.

Post-acute care transitions during COVID-19: Racial, ethnic, and socioeconomic differences in older adults with Alzheimer's disease and related dementia.

BACKGROUND: Differences in the post-acute care (PAC) destinations among racial, ethnic, and socioeconomic groups have been documented before the COVID-19 pandemic. Yet, the pandemic's impact on these differences remains unknown. We examined the impact of the COVID-19 pandemic on PAC destinations and its variation by individual race, ethnicity, and socioeconomic status among community-dwelling older adults with Alzheimer's disease and related dementia (ADRD). METHODS: We linked 2019-2021 national data (Medicare claims, Minimum Data Set, Master Beneficiary Summary File) and several publicly available datasets, including Provider of Services File, Area Deprivation Index, Area Health Resource File, and COVID-19 infection data. PAC discharge destinations included skilled nursing facilities (SNFs), home health agencies (HHA), and homes without services. Key variables of interest included individual race, ethnicity, and Medicare-Medicaid dual status. The analytic cohort included 830,656 community-dwelling Medicare fee-for-service beneficiaries with ADRD who were hospitalized between 2019 and 2021. Regression models with hospital random effects and state-fixed effects were estimated, stratified by the time periods, and adjusted for the individual, hospital, and county-level covariates. RESULTS: SNF discharges decreased while home and HHA discharges increased during the pandemic. The trend was more prominent among racial and ethnic minoritized groups and even more so among dual-eligible beneficiaries. For instance, the reduction in the probabilities of SNF admissions between the pre-pandemic period and the 2nd year of COVID was 4.6 (White non-duals), 18.5 (White duals), 8.7 (Black non-duals), and 20.1 (Black duals) percentage-point, respectively. We also found that non-duals were more likely to replace SNF with HHA services, while duals were more likely to be discharged home without HHA. CONCLUSIONS: The COVID-19 pandemic significantly impacted PAC destinations for individuals with ADRD, especially among socioeconomically disadvantaged and racial and ethnic minoritized populations. Future research is needed to understand if and how these transitions may have affected health outcomes.

Morphometrics predicts the differential regurgitant fraction in bilateral pulmonary arteries of patients with repaired tetralogy of fallot.

In patients with repaired tetralogy of Fallot (rTOF), the regurgitant fraction (RF) in left pulmonary artery (LPA) and right pulmonary artery (RPA) is usually unequal. The morphometrics may play a crucial role in this RF discrepancy. Cardiovascular MR of 79 rTOF patients and 20 healthy controls were retrospectively enrolled. Forty-four from the 79 patients were matched in age, sex and body surface area to the 20 controls and were investigated for: (1) phase-contrast flow of main pulmonary artery (MPA), LPA, and RPA; (2) vascular angles: the angles between the thoracic anterior-posterior line (TAPL) with MPA (θM-AP), MPA with RPA (θM-R), and MPA with LPA (θM-L); (3) cardiac angle, the angle between TAPL and the interventricular septum; (4) area ratio of bilateral lung and hemithorax regions. Compared with the 20 controls, the 44 rTOF patients exhibited wider θM-AP, sharper θM-L angle, and a smaller θM-L/θM-R ratio. In the 79 rTOF patients, LPA showed lower forward, backward, and net flow, and greater RF as compared with RPA. Multivariate analysis showed that the RF of LPA was negatively associated with the θM-L/θM-R ratio and the age at surgery (R2 = 0.255). Conversely, the RF of RPA was negatively associated with the left lung/left hemithorax area ratio and cross-sectional area (CSA) of LPA, and positively associated with CSA of RPA and MPA (R2 = 0.366). In rTOF patients, the RF of LPA is more severe than that of RPA, which may be related to the vascular morphometrics. Different morphometric parameters are independently associated with the RF of LPA or RPA, which may offer potential insights for surgical strategies.

Multi-average high-acceleration modified volumetric interpolated breath-hold examination (VIBE) for free-breathing multiphase contrast-enhanced liver MRI: a comparative study with breath-hold VIBE.

BACKGROUND: Breath-hold volumetric interpolated breath-hold examination (BH-VIBE) of multiphase contrast-enhanced liver magnetic resonance imaging (MPCE-LMRI) requires good cooperative individuals to comply with multiple breath-holds. PURPOSE: To develop a free-breathing modified VIBE (FB-mVIBE) as a substitute of BH-VIBE in MPCE-LMRI. MATERIAL AND METHODS: We modified VIBE with a high acceleration factor (2 × 2) and four averages to produce the mVIBE scan. A total of 90 individuals (40 men; mean age = 54.6 ± 10.0 years) who had received MPCE-LMRI as part of a voluntary health check-up for oncology survey were enrolled. Each participant was scanned in four phases (pre-contrast, arterial phase, venous phase, and delay phase), and each phase had two sequential scans. To encounter the timing effect of contrast enhancement, three scan orders were designed: BH-VIBE and FB-mVIBE (group A, n = 30); BH-VIBE and FB-VIBE (group B, n = 30); and FB-mVIBE and BH-VIBE (group C, n = 30). The comparisons included the objective measurements and 25 visual-score by two abdominal radiologists independently. RESULTS: Consistency between raters was observed for all three sequences (intraclass correlation coefficient [ICC] = 0.741-0.829). For rater 1, the mean scores of FB-mVIBE (23.67 ± 1.32) were equal to those of BH-VIBE (23.83 ± 1.98) in groups C and B (P = 0.852). The mean scores of FB-mVIBE (22.07 ± 3.02), but significantly higher than those of FB-VIBE (14.7 ± 3.41) in groups A and B (P <0.001). Similar scores were found for rater 2. The objective measurement of FB-mVIBE were equal to or higher than BH-VIBE and markedly superior to FB-VIBE. CONCLUSION: FB-mVIBE is a practical alternative to BH-VIBE for individuals who cannot cooperate with multiple breath-holds for MPCE-LMRI.

Denosumab Decreases Epicardial Adipose Tissue Attenuation in Dialysis Patients with Secondary Hyperparathyroidism and Low Bone Mass.

INTRODUCTION: Denosumab preceding elective surgery is an alternative option when parathyroidectomy is not immediately possible. Denosumab (an osteoprotegerin mimic) may play a role in the cardiovascular system, which is reflected in the features of epicardial adipose tissue (EAT) and coronary artery calcification (CAC). METHODS: We investigated the effects of denosumab on EAT attenuation (EATat) and CAC in dialysis patients with secondary hyperparathyroidism (SHPT). This cohort study included patients on dialysis with SHPT. The baseline characteristics of dialysis patients and propensity score-matched non-dialysis patients were compared. Computed tomography scans of the dialysis patients (dialysis group with denosumab, n = 24; dialysis group without denosumab, n = 21) were obtained at baseline and at 6 months of follow-up. RESULTS: At baseline, the dialysis group patients had a higher EATat-median (-71.00 H ± 10.38 vs. -81.60 H ± 6.03; p < 0.001) and CAC (1,223 A [248.50-3,315] vs. 7 A [0-182.5]; p < 0.001) than the non-dialysis group. At follow-up, the dialysis group without denosumab showed an increase in Agatston score (1,319.50 A [238.00-2,587.50] to 1,552.00 A [335.50-2,952.50]; p = 0.001) without changes in EATat-median (-71.33 H ± 11.72 to -70.86 H ± 12.67; p = 0.15). The dialysis group with denosumab showed no change in Agatston score (1,132.2 A [252.25-3,260.5] to 1,199.50 A [324.25-2,995]; p = 0.19) but a significant decrease of EATat-median (-70.71 H ± 9.30 to -74.33 H ± 10.28; p = 0.01). CONCLUSIONS: Denosumab may reverse EATat and retard CAC progression in dialysis patients with SHPT.

Seeing through a robot's eyes: A cross-sectional exploratory study in developing a robotic screening technology for autism.

The present exploratory cross-sectional case-control study sought to develop a reliable and scalable screening tool for autism using a social robot. The robot HUMANE, installed with computer vision and linked with recognition technology, detected the direction of eye gaze of children. Children aged 3-8 (M = 5.52; N = 199) participated, 87 of whom had been confirmed with autism, 55 of whom were suspected to have autism, and 57 of whom were not considered to cause any concern for having autism. Before a session, a human experimenter instructed HUMANE to narrate a story to a child. HUMANE prompted the child to return his/her eye gaze to the robot if the child looked away, and praised the child when it re-established its eye gaze quickly after a prompt. The reliability of eye gaze detection was checked across all pairs of human raters and HUMANE and reached 0.90, indicating excellent interrater agreement. Using the pre-specified reference standard (Autism Spectrum Quotient), the sensitivity and specificity of the index tests (i.e., the number of robot prompts and duration of inattentiveness) reached 0.88 or above and the Diagnostic Odds Ratios were beyond 190. These results show that social robots may detect atypical eye patterns, suggesting a potential future for screening autism using social robots.

The impact of serum estradiol and progesterone levels during implantation on obstetrical complications and perinatal outcomes in frozen embryo transfer.

BACKGROUND: This study sought to evaluate obstetric complications and perinatal outcomes in frozen embryo transfer (FET) using either a natural cycle (NC-FET) or a hormone therapy cycle (HT-FET). Furthermore, we investigated how serum levels of estradiol (E2) and progesterone (P4) on the day of and 3 days after embryo transfer (ET) correlated with clinical outcomes in the two groups. METHODS: We conducted a retrospective, single-center study from January 1, 2015, to December 31, 2019. The study included couples who underwent NC-FET or HT-FET resulting in a singleton live birth. Serum levels of E2 and P4 were measured on the day of and 3 days after ET. The primary outcomes assessed were preterm birth rate, low birth weight, macrosomia, hypertensive disorders in pregnancy, gestational diabetes mellitus, postpartum hemorrhage, and placenta-related complications. RESULTS: A total of 229 singletons were included, with 49 in the NC-FET group and 180 in the HT-FET group. There were no significant differences in obstetric complications and perinatal outcomes between the two groups. The NC-FET group had significantly higher serum levels of P4 (17.2 ng/mL vs 8.85 ng/mL; p < 0.0001) but not E2 (144 pg/mL vs 147 pg/mL; p = 0.69) on the day of ET. Additionally, 3 days after ET, the NC-FET group had significantly higher levels of both E2 (171 pg/mL vs 140.5 pg/mL; p = 0.0037) and P4 (27.3 ng/mL vs 11.7 ng/mL; p < 0.0001) compared with the HT-FET group. CONCLUSION: Our study revealed that although there were significant differences in E2 and P4 levels around implantation between the two groups, there were no significant differences in obstetric complications and perinatal outcomes. Therefore, the hormonal environment around implantation did not appear to be the primary cause of differences in obstetric and perinatal outcomes between the two EM preparation methods used in FET.

Low-dose CT screening among never-smokers with or without a family history of lung cancer in Taiwan: a prospective cohort study.

BACKGROUND: In Taiwan, lung cancers occur predominantly in never-smokers, of whom nearly 60% have stage IV disease at diagnosis. We aimed to assess the efficacy of low-dose CT (LDCT) screening among never-smokers, who had other risk factors for lung cancer. METHODS: The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) was a nationwide, multicentre, prospective cohort study done at 17 tertiary medical centres in Taiwan. Eligible individuals had negative chest radiography, were aged 55-75 years, had never smoked or had smoked fewer than 10 pack-years and stopped smoking for more than 15 years (self-report), and had one of the following risk factors: a family history of lung cancer; passive smoke exposure; a history of pulmonary tuberculosis or chronic obstructive pulmonary disorders; a cooking index of 110 or higher; or cooking without using ventilation. Eligible participants underwent LDCT at baseline, then annually for 2 years, and then every 2 years up to 6 years thereafter, with follow-up assessments at each LDCT scan (ie, total follow-up of 8 years). A positive scan was defined as a solid or part-solid nodule larger than 6 mm in mean diameter or a pure ground-glass nodule larger than 5 mm in mean diameter. Lung cancer was diagnosed through invasive procedures, such as image-guided aspiration or biopsy or surgery. Here, we report the results of 1-year follow-up after LDCT screening at baseline. The primary outcome was lung cancer detection rate. The p value for detection rates was estimated by the χ2 test. Univariate and multivariable logistic regression analyses were used to assess the association between lung cancer incidence and each risk factor. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LDCT screening were also assessed. This study is registered with ClinicalTrials.gov, NCT02611570, and is ongoing. FINDINGS: Between Dec 1, 2015, and July 31, 2019, 12 011 participants (8868 females) were enrolled, of whom 6009 had a family history of lung cancer. Among 12 011 LDCT scans done at baseline, 2094 (17·4%) were positive. Lung cancer was diagnosed in 318 (2·6%) of 12 011 participants (257 [2·1%] participants had invasive lung cancer and 61 [0·5%] had adenocarcinomas in situ). 317 of 318 participants had adenocarcinoma and 246 (77·4%) of 318 had stage I disease. The prevalence of invasive lung cancer was higher among participants with a family history of lung cancer (161 [2·7%] of 6009 participants) than in those without (96 [1·6%] of 6002 participants). In participants with a family history of lung cancer, the detection rate of invasive lung cancer increased significantly with age, whereas the detection rate of adenocarcinoma in situ remained stable. In multivariable analysis, female sex, a family history of lung cancer, and age older than 60 years were associated with an increased risk of lung cancer and invasive lung cancer; passive smoke exposure, cumulative exposure to cooking, cooking without ventilation, and a previous history of chronic lung diseases were not associated with lung cancer, even after stratification by family history of lung cancer. In participants with a family history of lung cancer, the higher the number of first-degree relatives affected, the higher the risk of lung cancer; participants whose mother or sibling had lung cancer were also at an increased risk. A positive LDCT scan had 92·1% sensitivity, 84·6% specificity, a PPV of 14·0%, and a NPV of 99·7% for lung cancer diagnosis. INTERPRETATION: TALENT had a high invasive lung cancer detection rate at 1 year after baseline LDCT scan. Overdiagnosis could have occurred, especially in participants diagnosed with adenocarcinoma in situ. In individuals who do not smoke, our findings suggest that a family history of lung cancer among first-degree relatives significantly increases the risk of lung cancer as well as the rate of invasive lung cancer with increasing age. Further research on risk factors for lung cancer in this population is needed, particularly for those without a family history of lung cancer. FUNDING: Ministry of Health and Welfare of Taiwan.

Effect of extra-low dose levothyroxine supplementation on pregnancy outcomes in women with subclinical hypothyroidism undergoing in vitro fertilization and embryo transfer.

OBJECTIVE: This study was undertaken to test the therapeutic effect of extra-low dose of levothyroxine (LT4; 25 mcg/day) to preconception and pregnant women with subclinical hypothyroidism (SCH). MATERIALS AND METHODS: This is a retrospective study, SCH women who succeeded in their first in vitro fertilization (IVF) cycle between January 1, 2018, to December 31, 2020 were included. SCH is defined as normal serum free thyroxine (T4) level and an elevated serum thyroid stimulating hormone (TSH) level >4 mIU/L. Extra-low dose of levothyroxine (LT4; 25 mcg/day) was prescribed to the SCH women from the establish of diagnosis of SCH to the end of pregnancy. The pregnancy outcomes (miscarriage, live birth, preterm birth, and small for gestational age baby) were compared to the euthyroid pregnant women. RESULTS: Totally, 589 women were screened, and 317 cases received their first time IVF treatment. 167 women were clinically pregnant after IVF treatment, 155 of them were euthyroid and 12 of these women were diagnosed to have SCH. The average age of the participants was 35 years old. There were no significant differences in age, body mass index (BMI), anti-müllerian hormone (AMH), types of embryo transfer, number of embryos to transfer, or embryo stage during transfer between two groups. The live birth rate, miscarriage rate, and preterm birth rate in women with SCH supplemented with extra-low dose of LT4 were non-inferior to euthyroid patients (miscarriage rate: P = 0.7112; live birth rate: P = 0.7028; preterm delivery: P = 0.2419; small for gestational age: P = 0.2419). CONCLUSION: Our result demonstrated that supplementation with extra-low dose of levothyroxine at 25 mcg/day to SCH women can produce the comparable obstetrical and neonatal outcome as that in euthyroid pregnant women. Accordingly, we suggest extra-low-dose of levothyroxine may be considered as a safe and effective alternative for those SCH pregnant women who were not tolerated to the standard dose of levothyroxine.

Endosomal Arl4A attenuates EGFR degradation by binding to the ESCRT-II component VPS36.

Ligand-induced epidermal growth factor receptor (EGFR) endocytosis followed by endosomal EGFR signaling and lysosomal degradation plays important roles in controlling multiple biological processes. ADP-ribosylation factor (Arf)-like protein 4 A (Arl4A) functions at the plasma membrane to mediate cytoskeletal remodeling and cell migration, whereas its localization at endosomal compartments remains functionally unknown. Here, we report that Arl4A attenuates EGFR degradation by binding to the endosomal sorting complex required for transport (ESCRT)-II component VPS36. Arl4A plays a role in prolonging the duration of EGFR ubiquitinylation and deterring endocytosed EGFR transport from endosomes to lysosomes under EGF stimulation. Mechanistically, the Arl4A-VPS36 direct interaction stabilizes VPS36 and ESCRT-III association, affecting subsequent recruitment of deubiquitinating-enzyme USP8 by CHMP2A. Impaired Arl4A-VPS36 interaction enhances EGFR degradation and clearance of EGFR ubiquitinylation. Together, we discover that Arl4A negatively regulates EGFR degradation by binding to VPS36 and attenuating ESCRT-mediated late endosomal EGFR sorting.

Genome-wide comprehensive characterization and transcriptomic analysis of AP2/ERF gene family revealed its role in seed oil and ALA formation in perilla (Perilla frutescens).

Perilla (Perilla frutescens) is a potential specific oilseed crop with an extremely high α-linolenic acid (ALA) content in its seeds. AP2/ERF transcription factors (TFs) play important roles in multiple biological processes. However, limited information is known about the regulatory mechanism of the AP2/ERF family in perilla's oil accumulation. In this research, we identified 212 AP2/ERF family members in the genome of perilla, and their domain characteristics, collinearity, and sub-genome differentiation were comprehensively analyzed. Transcriptome sequencing revealed that genes encoding key enzymes involved in oil biosynthesis (e.g., ACCs, KASII, GPAT, PDAT and LPAAT) were up-regulated in the high-oil variety. Moreover, the endoplasmic reticulum-localized FAD2 and FAD3 were significantly up-regulated in the high-ALA variety. To investigate the roles of AP2/ERFs in lipid biosynthesis, we conducted a correlation analysis between non-redundant AP2/ERFs and key lipid metabolism genes using WGCNA. A significant correlation was found between 36 AP2/ERFs and 90 lipid metabolism genes. Among them, 12 AP2/ERFs were identified as hub genes and showed significant correlation with lipid synthase genes (e.g., FADs, GPAT and ACSL) and key regulatory TFs (e.g., LEC2, IAA, MYB, UPL3). Furthermore, gene expression analysis identified three AP2/ERFs (WRI, ABI4, and RAVI) potentially playing an important role in the regulation of oil accumulation in perilla. Our study suggests that PfAP2/ERFs are important regulatory TFs in the lipid biosynthesis pathway, providing a foundation for the molecular understanding of oil accumulation in perilla and other oilseed crops.

Clinical risk factors and outcomes of young patients with acute ST segment elevation myocardial infarction: a retrospective study.

BACKGROUND: This study aimed to analysis the clinical characteristics and prognosis of acute STEMI in patients aged ≤ 45 years. METHODS: Seven hundred and one patients with STEMI from Liaocheng People's Hospital from January 2018 to March 2021 were included in this study. Clinical characteristics, management, and outcomes (average follow-up: 11.5 months) were compared between patients aged ≤ 45 years and those aged > 45 years. RESULTS: Of the patients with STEMI who underwent primary percutaneous coronary intervention, 108 (15.4%) were aged ≤ 45 years. Compared to the older group, the younger patient group included more males, current smokers, and those with alcohol use disorder (AUD) or a family history of ischaemic heart disease (IHD). The culprit vessel in young patients was the left anterior descending (LAD) artery (60% vs. 45.9%, P = 0.031), which may have been due to smoking (odds ratio, 3.5; 95% confidence interval: 1.12-10.98, P = 0.042). Additionally, young patients presented with higher low-density lipoprotein and lower high-density lipoprotein levels than older patients; uric acid levels were also significantly higher in younger patients than that in the older group. Diabetes showed a trend toward major adverse cardiovascular events (MACE) in both groups; age and sex were both independent predictors of MACE in older patients. CONCLUSION: More patients who were smokers, had AUD, or a family history of IHD were present in the young patient group. Hyperuricaemia (but not dyslipidaemia) was a prevalent risk factor in patients aged ≤ 45 years. Diabetes should be controlled to reduce cardiovascular events in young patients.

Can Low-Iodine, Low-Radiation-Dose CT Aortogram Reliably Detect Endoleak after Endovascular Aneurysm Repair of the Aorta?

OBJECTIVE: Double-low CT aortography (DLCTA) is increasingly used in follow-up studies of aortic aneurysm after endovascular aneurysm repair (EVAR). However, whether DLCTA can reliably detect the presence of endoleak is not clear. METHODS: From February 2014 to October 2019, patients who received EVAR, underwent CT surveillance, and had at least one standard CTA protocol (120 kVp, 400 mg I/kg) and one DLCTA (70-80 kVp, 200 mg I/kg) were included. The integrated findings of the standard CTA and sequential change were considered as the reference standard for the presence of endoleak. RESULTS: In all, 36 patients received TEVAR and 24 patients received EVAR; 62 standard CTA and 167 DLCTA results were analyzed. There were 2 type I (3.3%) and 12 type II (20.0%) endoleaks in 14 patients (23.3%). The performance of DLCTA in the diagnosis of endoleak reached 100% accuracy compared to that of standard CTA in case of the correction of CT findings by an expert second reading. Compared to the standard CTA, DLCTA scan reduced the radiation dose by 71% and the iodine dose by 50%. CONCLUSIONS: DLCTA with 70-80 kVp and 200 mg I/kg can reliably detect the presence of endoleak after TEVAR/EVAR.

Corrigendum: Clinical radiomics-based machine learning versus three-dimension convolutional neural network analysis for differentiation of thymic epithelial tumors from other prevascular mediastinal tumors on chest computed tomography scan.

[This corrects the article DOI: 10.3389/fonc.2023.1105100.].

Clinical radiomics-based machine learning versus three-dimension convolutional neural network analysis for differentiation of thymic epithelial tumors from other prevascular mediastinal tumors on chest computed tomography scan.

Purpose: To compare the diagnostic performance of radiomic analysis with machine learning (ML) model with a convolutional neural network (CNN) in differentiating thymic epithelial tumors (TETs) from other prevascular mediastinal tumors (PMTs). Methods: A retrospective study was performed in patients with PMTs and undergoing surgical resection or biopsy in National Cheng Kung University Hospital, Tainan, Taiwan, E-Da Hospital, Kaohsiung, Taiwan, and Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan between January 2010 and December 2019. Clinical data including age, sex, myasthenia gravis (MG) symptoms and pathologic diagnosis were collected. The datasets were divided into UECT (unenhanced computed tomography) and CECT (enhanced computed tomography) for analysis and modelling. Radiomics model and 3D CNN model were used to differentiate TETs from non-TET PMTs (including cyst, malignant germ cell tumor, lymphoma and teratoma). The macro F1-score and receiver operating characteristic (ROC) analysis were performed to evaluate the prediction models. Result: In the UECT dataset, there were 297 patients with TETs and 79 patients with other PMTs. The performance of radiomic analysis with machine learning model using LightGBM with Extra Tree (macro F1-Score = 83.95%, ROC-AUC = 0.9117) had better performance than the 3D CNN model (macro F1-score = 75.54%, ROC-AUC = 0.9015). In the CECT dataset, there were 296 patients with TETs and 77 patients with other PMTs. The performance of radiomic analysis with machine learning model using LightGBM with Extra Tree (macro F1-Score = 85.65%, ROC-AUC = 0.9464) had better performance than the 3D CNN model (macro F1-score = 81.01%, ROC-AUC = 0.9275). Conclusion: Our study revealed that the individualized prediction model integrating clinical information and radiomic features using machine learning demonstrated better predictive performance in the differentiation of TETs from other PMTs at chest CT scan than 3D CNN model.