Predictors for temporary stomas non-closure among non-metastatic rectal cancer patients undergoing curative resection: a retrospective analysis.

BACKGROUND: The primary treatment for non-metastatic rectal cancer is curative resection. However, sphincter-preserving surgery may lead to complications. This study aims to develop a predictive model for stoma non-closure in rectal cancer patients who underwent curative-intent low anterior resection. METHODS: Consecutive patients diagnosed with non-metastatic rectal cancer between January 2005 and December 2017, who underwent low anterior resection, were retrospectively included in the Chang Gung Memorial Foundation Institutional Review Board. A comprehensive evaluation and analysis of potential risk factors linked to stoma non-closure were performed. RESULTS: Out of 956 patients with temporary stomas, 10.3% (n = 103) experienced non-closure primarily due to cancer recurrence and anastomosis-related issues. Through multivariate analysis, several preoperative risk factors significantly associated with stoma non-closure were identified, including advanced age, anastomotic leakage, positive nodal status, high preoperative CEA levels, lower rectal cancer presence, margin involvement, and an eGFR below 30 mL/min/1.73m2. A risk assessment model achieved an AUC of 0.724, with a cutoff of 2.5, 84.5% sensitivity, and 51.4% specificity. Importantly, the non-closure rate could rise to 16.6% when more than two risk factors were present, starkly contrasting the 3.7% non-closure rate observed in cases with a risk score of 2 or below (p < 0.001). CONCLUSION: Prognostic risk factors associated with the non-closure of a temporary stoma include advanced age, symptomatic anastomotic leakage, nodal status, high CEA levels, margin involvement, and an eGFR below 30 mL/min/1.73m2. Hence, it is crucial for surgeons to evaluate these factors and provide patients with a comprehensive prognosis before undergoing surgical intervention.

Coffee consumption was associated with a lower prevalence of airflow limitation in postmenopausal women.

BACKGROUND: Several studies have suggested a potential correlation between menopause and airflow limitation. However, the presence of protective factors in postmenopausal women remains uncertain. Therefore, our study seeks to examine potential protective factors associated with a reduced prevalence of airflow limitation among postmenopausal women. METHODS: Postmenopausal women were recruited from the Taiwan Biobank for this cross-sectional study. Airflow limitation was defined by a forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) ratio <0.7. The participants were categorized into two groups: non-coffee drinkers and coffee drinkers, and the association between coffee consumption and airflow limitation was examined using binary logistic regression models. RESULTS: A total of 8149 women with available information were enrolled. Compared to the non-coffee drinkers, the coffee drinkers had a significantly lower prevalence of airflow limitation (7% vs. 5%). The odds ratio (OR) for airflow limitation was lower in the coffee drinkers than in the non-coffee drinkers (OR = 0.77; 95% confidence interval [CI] = 0.63 to 0.94) after adjusting for confounding factors. We also examined the association between daily coffee consumption in cups and airflow limitation. The women who consumed ≥2 cups of coffee per day had an OR of 0.74 (95% CI = 0.59 to 0.94) compared to those who did not consume coffee. CONCLUSIONS: Our results suggest that habitual coffee consumption is associated with a reduction in the prevalence of airflow limitation in postmenopausal women, warranting further prospective studies to explore possible causal effects and mechanisms.

Evaluation of spatial and temporal changes in illicit drug use in the Taipei metropolitan area via wastewater-based epidemiology.

Taiwan, identified as pivotal in the Asian drug trafficking chain, has been experiencing a surge in illicit drug-related issues. Wastewater-based epidemiology (WBE) has emerged as a promising approach for comprehensive evaluation of actual illicit drug usage. This study presents the first WBE investigation of illicit drug consumption in Taiwan based on the analysis of wastewater from four wastewater treatment plants (WWTPs) in the Taipei metropolitan area. Additionally, it demonstrates a high correlation between the amounts of illicit drugs seized and influent concentrations over an extended period of time. The reliability of solid-phase extraction and analysis via high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was validated for 16 illicit drugs (methamphetamine, ketamine, cocaine, codeine, methadone, morphine, meperidine, fentanyl, sufentanil, para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA), 3,4-methylenedioxymethamphetamine (MDMA), cathinone, methcathinone, mephedrone (MEPH), and 4-methylethcathinone (4-MEC)). Methamphetamine, ketamine, and 4-MEC were consistently detected in all wastewater samples, underscoring their prevalence in the Taipei metropolitan area. Biochemical oxygen demand (BOD) and ammonia nitrogen (ammonia N) were employed to reduce uncertainty in estimations of population size during back-calculation of illicit drug consumption. The results indicate that methamphetamine was the most consumed drug (175-740 mg day-1 1000 people-1), followed by ketamine (22-280 mg day-1 1000 people-1). In addition, urban-related WWTPs exhibited higher consumption of methamphetamine and ketamine than did the suburban-related WWTP, indicating distinct illicit drug usage patterns between suburban and urban regions. Moreover, an examination of temporal trends in wastewater from the Dihua WWTP revealed a persistent predominance of ketamine and methamphetamine, consistent with statistical data pertaining to seizure quantities and urine test results. The study provides encouraging insight into spatial and temporal variations in illicit drug usage in the Taipei metropolitan area, emphasizing the complementary role of WBE in understanding trends in illicit drug abuse.

Exposure-Response to High PM 2.5 Levels for Cardiovascular Events in High-risk Older Adults in Taiwan.

Background: Multiple studies from countries with relatively lower PM 2.5 level demonstrated that acute and chronic exposure even at lower than recommended level, e.g., 9 µg/m 3 in the US increased the risk of cardiovascular (CV) events. However, limited studies using individual level data exist from countries with a wider range of PM levels to illustrate shape of the exposure-response curve throughout the range including > 20 µg/m 3 PM 2·5 concentrations. Taiwan with its policies reduced PM 2.5 over time provide opportunities to illustrate the dose response curves and how reductions of PM 2.5 over time correlated with CV events incidence in a nationwide sample. Methods: Using data from the 2009-2019 Taiwan National Health Insurance Database linked to nationwide PM2.5 data. We examined the shape and magnitude of the exposure-response curve between seasonal average PM 2·5 level and CV events-related hospitalizations among older adults at high-risk for CV events. We used history-adjusted marginal structural models including potential confounding by individual demographic factors, baseline comorbidities, and health service measures. To quantify the risk below and above 20 µg/m 3 we conducted stratified Cox regression. We also plotted PM 2.5 and CV events from 2009-2019 as well as average temperature as a comparison. Findings: Using the PM 2.5 concentration <15 µg/m 3 (Taiwan regulatory standard) as a reference, the seasonal average PM 2.5 concentration (15-23.5µg/m 3 and > 23.5 µg/m 3 ) were associated with hazard ration of 1.13 (95%CI 1.09-1.18) and 1.19 (95%CI 1.14-1.24), 1.07 (95%CI 1.03-1.11) and 1.14 (95%CI 1.10-1.18), 1.22 (95%CI 1.08-1.38) and 1.31 (95%CI 1.16-1.48), 1.04 (95%CI 0.98-1.10) and 1.10 (95%CI 1.04-1.16) respectively for HF, IS/TIA,PE/DVT and MI/ACS. A nonlinear relationship between PM 2·5 and CV events outcomes was observed at PM 2·5 levels above 20 µg/m 3 . Interpretation: A nonlinear exposure-response relationship between PM2·5 concentration and the incidence of cardiovascular events exists when PM2.5 is higher than the levels recommended by WHO Air Quality Guidelines. Further lowering PM2·5 levels beyond current regulatory standards may effectively reduce the incidence of cardiovascular events, particularly HF and DVT, and can lead to tangible health benefits in high-risk elderly population.

Chronic radiation proctitis refractory to steroid enema was successfully treated by metformin and sodium butyrate: a case report.

BACKGROUND: Radiation proctitis (RP) is a significant complication of pelvic radiation. Effective treatments for chronic RP are currently lacking. We report a case where chronic RP was successfully managed by metformin and butyrate (M-B) enema and suppository therapy. CASE PRESENTATION: A 70-year-old Asian male was diagnosed with prostate cancer of bilateral lobes, underwent definitive radiotherapy to the prostate of 76 Gy in 38 fractions and six months of androgen deprivation therapy. Despite a stable PSA nadir of 0.2 ng/mL for 10 months post-radiotherapy, he developed intermittent rectal bleeding, and was diagnosed as chronic RP. Symptoms persisted despite two months of oral mesalamine, mesalamine enema and hydrocortisone enema treatment. Transition to daily 2% metformin and butyrate (M-B) enema for one week led to significant improvement, followed by maintenance therapy with daily 2.0% M-B suppository for three weeks, resulting in continued reduction of rectal bleeding. Endoscopic examination and biopsy demonstrated a good therapeutic effect. CONCLUSIONS: M-B enema and suppository may be an effective treatment for chronic RP.

Mechanical shear flow regulates the malignancy of colorectal cancer cells.

Colorectal cancer (CRC) is notable for its high mortality and high metastatic characteristics. The shear force generated by bloodstream provides mechanical signals regulating multiple responses of cells, including metastatic cancer cells, dispersing in blood vessels. We, therefore, studied the effect of shear flow on circulating CRC cells in the present study. The CRC cell line SW620 was subjected to shear flow of 12.5 dynes/cm2 for 1 and 2 h separately. Resulting elevated caspase-9 and -3 indicated that shear flow initiated the apoptosis of SW620. Enlarged cell size associated with a higher level of cyclin D1 was coincident with the flow cytometric results indicating that the cell cycle was arrested at the G1 phase. An elevated phosphor-eNOSS1177 increased the production of nitric oxide and led to reactive oxygen species-mediated oxidative stress. Shear flow also regulated epithelial-mesenchymal transition (EMT) by increasing E-cadherin and ZO-1 while decreasing Snail and Twist1. The migration and invasion of sheared SW620 were also substantially decreased. Further investigations showed that mitochondrial membrane potential was significantly decreased, whereas mitochondrial mass and ATP production were not changed. In addition to the shear flow of 12.5 dynes/cm2, the expressions of EMT were compared at lower (6.25 dynes/cm2) and at higher (25 dynes/cm2) shear flow. The results showed that lower shear flow increased mesenchymal characteristics and higher shear flow increased epithelial characteristics. Shear flow reduces the malignancy of CRC in their metastatic dispersal that opens up new ways to improve cancer therapies by applying a mechanical shear flow device.

The interaction between 20-hydroxyecdysone and AMPK through PI3K activation in Chinese mitten crab, Eriocheir sinensis.

In crustaceans, the steroid hormone 20-hydroxyecdysone (20E) initiates molting, and the molting process is also regulated by energy metabolism. AMPK is an energy sensor and plays a critical role in systemic energy balance. Here, the regulatory mechanism in the interaction between 20E and AMPK was investigated in Chinese mitten crab, Eriocheir sinensis. The results showed that the 20E concentration and the mRNA expression levels of 20E receptors in hepatopancreas were down-regulated post AMPK activator (AICAR) treatment, and were up-regulated after AMPK inhibitor (Compound C) injection in crabs. Besides, the molt-inhibiting hormone (MIH) gene expression in eyestalk showed the opposite patterns in response to the AICAR and Compound C treatment, respectively. Further investigation found that there was a significant reduction in 20E concentration post PI3K inhibitor (LY294002) treatment, and the phosphorylation level of PI3K was increased in hepatopancreas after AMPK inhibitor injection. On the other hand, the positive regulation of PI3K-mediated activation of AMPK was also observed, the phosphorylation levels of AMPKα, AMPKß and PI3K in hepatopancreas were significantly increased post 20E injection. In addition, the phosphorylation levels of AMPKα and AMPKß induced by 20E were decreased after the injection of PI3K inhibitor. Taken together, these results suggest that the regulatory cross-talk between 20E and AMPK is likely to act through PI3K pathway in E. sinensis, which appeared to be helpful for a better understanding in molting regulation.

Broadband frequency comb generation through cascaded quadratic nonlinearity in thin-film lithium niobate microresonators.

Broadband frequency comb generation through cascaded quadratic nonlinearity remains experimentally untapped in free-space cavities with bulk χ(2) materials mainly due to the high threshold power and restricted ability of dispersion engineering. Thin-film lithium niobate (LN) is a good platform for nonlinear optics due to the tight mode confinement in a nano-dimensional waveguide, the ease of dispersion engineering, large quadratic nonlinearities, and flexible phase matching via periodic poling. Here we demonstrate broadband frequency comb generation through dispersion engineering in a thin-film LN microresonator. Bandwidths of 150 nm (80 nm) and 25 nm (12 nm) for center wavelengths at 1560 and 780 nm are achieved, respectively, in a cavity-enhanced second-harmonic generation (doubly resonant optical parametric oscillator). Our demonstration paves the way for pure quadratic soliton generation, which is a great complement to dissipative Kerr soliton frequency combs for extended interesting nonlinear applications.

Development and validation of a nomogram for predicting in-hospital mortality of intensive care unit patients with liver cirrhosis.

BACKGROUND: Liver cirrhosis patients admitted to intensive care unit (ICU) have a high mortality rate. AIM: To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver cirrhosis. METHODS: We extracted demographic, etiological, vital sign, laboratory test, comorbidity, complication, treatment, and severity score data of liver cirrhosis patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) and electronic ICU (eICU) collaborative research database (eICU-CRD). Predictor selection and model building were based on the MIMIC-IV dataset. The variables selected through least absolute shrinkage and selection operator analysis were further screened through multivariate regression analysis to obtain final predictors. The final predictors were included in the multivariate logistic regression model, which was used to construct a nomogram. Finally, we conducted external validation using the eICU-CRD. The area under the receiver operating characteristic curve (AUC), decision curve, and calibration curve were used to assess the efficacy of the models. RESULTS: Risk factors, including the mean respiratory rate, mean systolic blood pressure, mean heart rate, white blood cells, international normalized ratio, total bilirubin, age, invasive ventilation, vasopressor use, maximum stage of acute kidney injury, and sequential organ failure assessment score, were included in the multivariate logistic regression. The model achieved AUCs of 0.864 and 0.808 in the MIMIC-IV and eICU-CRD databases, respectively. The calibration curve also confirmed the predictive ability of the model, while the decision curve confirmed its clinical value. CONCLUSION: The nomogram has high accuracy in predicting in-hospital mortality. Improving the included predictors may help improve the prognosis of patients.

The applications of high-flow nasal cannulas in pediatric intensive care units in Taiwan.

BACKGROUND: /purpose: The use of high-flow nasal cannulas (HFNC) in patients admitted to the pediatric intensive care unit (PICU) has gradually increased worldwide; however, details on clinical efficacy remain limited in Taiwan. Therefore, we explored the clinical characteristics and outcomes of pediatric patients using HFNC in the PICU. METHODS: Medical records were retrospectively collected from pediatric patients (aged <18 years) who received HFNC support from December 2021 to January 2023 in the PICU of a medical center. Outcome parameters included treatment failure (defined as increased respiratory support to advanced non-invasive ventilators or intubations), duration of support from HFNC, and changes in clinical parameters after initiating HFNC. RESULTS: A total of 261 episodes of HFNC use were included, with a failure rate of 24.5% and a median support length of 4 days. Multivariable analysis showed that infant age (adjusted odds ratio [aOR]: 2.1, p = 0.02) and accompanying complex chronic disease (aOR: 4.4, p = 0.014) were risk factors for treatment failure and a diagnosis of asthma or bronchiolitis had a lower hazard of treatment failure (aOR: 0.29, p = 0.025) than other diagnoses did. Improvements in clinical parameters, including pulse rate, respiratory rate, SpO2, and CO2 levels, were observed 24 h after the initiation of HFNC. CONCLUSION: The application of HFNC in the PICU in Taiwan is effective but should be performed with care in infants with accompanying complex chronic diseases. In addition to low treatment failure, HFNC utilizations stabilized the clinical parameters of children with asthma/bronchiolitis within one day.

Decreasing mitochondrial fission ameliorates HIF-1α-dependent pathological retinal angiogenesis.

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 µM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg-1·d-1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.

Maternal folic acid supplementation during pregnancy in association with childhood overweight or obesity.

OBJECTIVE: This study aimed to examine associations of maternal folic acid supplementation (FAS) during pregnancy with childhood overweight or obesity (OWO) or adiposity. METHODS: In a population-based cohort of 1479 children, maternal FAS during pregnancy was assessed retrospectively by questionnaires. BMI and body fat percentages were measured at a mean age of 6.4 years. Pertinent factors were accounted for in data analyses. RESULTS: Maternal FAS during pregnancy was negatively associated with OWO (adjusted odds ratio: 0.70; 95% CI: 0.50 to 0.99). There were inverse associations of maternal FAS during pregnancy with BMI z score (ß: -0.22; 95% CI: -0.39 to -0.05), whole body fat percentage (ß: -1.28; 95% CI: -2.27 to -0.30), trunk fat percentage (ß: -1.41; 95% CI: -2.78 to -0.04), and limb fat percentage (ß: -1.31; 95% CI: -2.32 to -0.30). Stratified analyses found inverse associations of FAS during pregnancy with OWO, BMI z score, and body fat percentages predominantly among children without breastfeeding and whose parents had a below-tertiary educational level. CONCLUSIONS: This study provides novel evidence that maternal FAS during pregnancy was significantly associated with a decreased risk of childhood OWO and adiposity, particularly among children with no breastfeeding and lower parental educational level.

The association between body mass index and osteoporosis in a Taiwanese population: a cross-sectional and longitudinal study.

This study investigates the correlation between body mass index (BMI) and osteoporosis utilizing data from the Taiwan Biobank. Initially, a comprehensive analysis of 119,009 participants enrolled from 2008 to 2019 was conducted to assess the association between BMI and osteoporosis prevalence. Subsequently, a longitudinal cohort of 24,507 participants, initially free from osteoporosis, underwent regular follow-ups every 2-4 years to analyze the risk of osteoporosis development, which was a subset of the main cohort. Participants were categorized into four BMI groups: underweight (BMI < 18.5 kg/m2), normal weight (18.5 kg/m2 ≤ BMI < 24 kg/m2), overweight (24 kg/m2 ≤ BMI < 27 kg/m2), and obese groups (BMI ≥ 27 kg/m2). A T-score ≤ - 2.5 standard deviations below that of a young adult was defined as osteoporosis. Overall, 556 (14.1%), 5332 (9.1%), 2600 (8.1%) and 1620 (6.7%) of the participants in the underweight, normal weight, overweight and obese groups, respectively, had osteoporosis. A higher prevalence of osteoporosis was noted in the underweight group compared with the normal weight group (odds ratio [OR], 2.20; 95% confidence interval [95% CI], 1.99 to 2.43; p value < 0.001) in multivariable binary logistic regression analysis. Furthermore, in the longitudinal cohort during a mean follow-up of 47 months, incident osteoporosis was found in 61 (9%), 881 (7.2%), 401 (5.8%) and 213 (4.6%) participants in the underweight, normal weight, overweight and obese groups, respectively. Multivariable Cox proportional hazards analysis revealed that the risk of incident osteoporosis was higher in the underweight group than in the normal weight group (hazard ratio [HR], 1.63; 95% CI 1.26 to 2.12; p value < 0.001). Our results suggest that BMI is associated with both the prevalence and the incidence of osteoporosis. In addition, underweight is an independent risk factor for developing osteoporosis. These findings highlight the importance of maintaining normal weight for optimal bone health.

Preoperative handgrip strength can predict early postoperative shoulder function in patients undergoing arthroscopic rotator cuff repair.

BACKGROUND: Rotator cuff tears (RCTs) are a common musculoskeletal disorder, and arthroscopic rotator cuff repair (ARCR) is widely performed for tendon repair. Handgrip strength correlates with rotator cuff function; however, whether preoperative grip strength can predict functional outcomes in patients undergoing ARCR remains unknown. This study aimed to investigate the correlation between preoperative grip strength and postoperative shoulder function following ARCR. METHODS: A total of 52 patients with full-thickness repairable RCTs were prospectively enrolled. Baseline parameters, namely patient characteristics and intraoperative findings, were included for analysis. Postoperative shoulder functional outcomes were assessed using the Quick Disabilities of the Arm, Shoulder, and Hand (QDASH) questionnaire and Constant-Murley scores (CMSs). Patients were followed up and evaluated at three and six months after ARCR. The effects of baseline parameters on postoperative outcomes were measured using generalized estimating equations. RESULTS: At three and six months postoperatively, all clinical outcomes evaluated exhibited significant improvement from baseline following ARCR. Within 6 months postoperatively, higher preoperative grip strength was significantly correlated with higher CMSs (ß = 0.470, p = 0.022), whereas increased numbers of total suture anchors were significantly correlated with decreased CMSs (ß = - 4.361, p = 0.03). Higher body mass index was significantly correlated with higher postoperative QDASH scores (ß = 1.561, p = 0.03) during follow-up. CONCLUSIONS: Higher baseline grip strength predicts more favorable postoperative shoulder function following ARCR. A preoperative grip strength test in orthopedic clinics may serve as a predictor for postoperative shoulder functional recovery in patients undergoing ARCR.

Assessment of the Effect of Rehmannia glutinosa Leaf Extract in Maintaining Skin Health: A Proof-of-Concept, Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

Purpose: A double-blind, placebo-controlled, randomized, proof-of-concept trial aimed to evaluate the efficacy and safety of VerbasnolTM [Rehmannia glutinosa Libosch leaf-based extract (RGLE)] in females, with moderate to severe acne vulgaris. Participants and Methods: Twenty-two females aged 18 to 35 years having moderate to severe acne with Global Acne Grading System (GAGS) scores of 19 to 38 were included in the study and were randomized in a 1:1 ratio to receive either one capsule (100 mg/day) of RGLE or placebo orally after breakfast for 56 days. The primary outcome was a change in acne severity measured by the GAGS compared to the placebo on day 56. The secondary outcomes were changes in the number of inflammatory acne lesions, facial sebum secretion, quality of life, local pain and itching, skin wrinkle severity, and other skin characteristics, including radiance, luminosity, smoothness, texture, firmness, and hydration. Additionally, the percentage of responders and global tolerability and efficacy were evaluated. Results: The mean GAGS score was reduced by 21.72% and 14.20% on day 28 in RGLE (n=10) and placebo groups (n=12), respectively, which further reduced in both groups on day 56. The RGLE group reported better improvement in other skin characteristics on day 56. No safety or tolerability concerns were reported for the extract. RGLE reduced acne and improved the skin quality in females compared to placebo as early as 28 days of supplementation. Conclusion: RGLE supplementation at a dose of 100 mg/day has provided a clinically relevant decrease in acne severity and improved the skin hydration and quality of life of the participants with acne after 56 days of dose administration.

Automated osteoporosis classification and T-score prediction using hip radiographs via deep learning algorithm.

Background: Despite being the gold standard for diagnosing osteoporosis, dual-energy X-ray absorptiometry (DXA) is an underutilized screening tool for osteoporosis. Objectives: This study proposed and validated a controllable feature layer of a convolutional neural network (CNN) model with a preprocessing image algorithm to classify osteoporosis and predict T-score on the proximal hip region via simple hip radiographs. Design: This was a single-center, retrospective study. Methods: An image dataset of 3460 unilateral hip images from 1730 patients (age ⩾50 years) was retrospectively collected with matched DXA assessment for T-score for the targeted proximal hip regions to train (2473 unilateral hip images from 1430 patients) and test (497 unilateral hip images from 300 patients) the proposed CNN model. All images were processed with a fully automated CNN model, X1AI-Osteo. Results: The proposed screening tool illustrated a better performance (sensitivity: 97.2%; specificity: 95.6%; positive predictive value: 95.7%; negative predictive value: 97.1%; area under the curve: 0.96) than the open-sourced CNN models in predicting osteoporosis. Moreover, when combining variables, including age, body mass index, and sex as features in the training metric, there was high consistency in the T-score on the targeted hip regions between the proposed CNN model and the DXA (r = 0.996, p < 0.001). Conclusion: The proposed CNN model may identify osteoporosis and predict T-scores on the targeted hip regions from simple hip radiographs with high accuracy, highlighting the future application for population-based opportunistic osteoporosis screening with low cost and high adaptability for a broader population at risk. Trial registration: TMU-JIRB N201909036.

Acute Pancreatitis in Pregnancy: A Propensity Score Matching Analysis and Dynamic Nomogram for Risk Assessment.

BACKGROUND: Acute pancreatitis is easily confused with abdominal pain symptoms, and it could lead to serious complications for pregnant women and fetus, the mortality was as high as 3.3% and 11.6-18.7%, respectively. However, there is still lack of sensitive laboratory markers for early diagnosis of APIP and authoritative guidelines to guide treatment. OBJECTIVE: The purpose of this study was to explore the risk factors of acute pancreatitis in pregnancy, establish, and evaluate the dynamic prediction model of risk factors in acute pancreatitis in pregnancy patients. STUDY DESIGN: Clinical data of APIP patients and non-pregnant acute pancreases patients who underwent regular antenatal check-ups during the same period were collected. The dataset after propensity matching was randomly divided into training set and verification set at a ratio of 7:3. The model was constructed using Logistic regression, least absolute shrinkage and selection operator regression, R language and other methods. The training set model was used to construct the diagnostic nomogram model and the validation set was used to validate the model. Finally, the accuracy and clinical practicability of the model were evaluated. RESULTS: A total of 111 APIP were included. In all APIP patients, hyperlipidemic pancreatitis was the most important reason. The levels of serum amylase, creatinine, albumin, triglyceride, high-density lipoprotein cholesterol, and apolipoprotein A1 were significantly different between the two groups. The propensity matching method was used to match pregnant pancreatitis patients and pregnant non-pancreatic patients 1:1 according to age and gestational age, and the matching tolerance was 0.02. The multivariate logistic regression analysis of training set showed that diabetes, triglyceride, Body Mass Index, white blood cell, and C-reactive protein were identified and entered the dynamic nomogram. The area under the ROC curve of the training set was 0.942 and in validation set was 0.842. The calibration curve showed good predictive in training set, and the calibration performance in the validation set was acceptable. The calibration curve showed the consistency between the nomogram model and the actual probability. CONCLUSION: The dynamic nomogram model we constructed to predict the risk factors of acute pancreatitis in pregnancy has high accuracy, discrimination, and clinical practicability.

Up-regulation of inflammatory, oxidative stress, and apoptotic mediators via inflammatory, oxidative stress, and apoptosis-associated pathways in bovine endometritis.

Endometritis is the inflammation of the endothelial lining of the uterine lumen and is multifactorial in etiology. Escherichia (E.) coli is a Gram-negative bacteria, generally considered as a primary causative agent for bovine endometritis. Bovine endometritis is characterized by the activation of Toll-like receptors (TLRs) by E. coli, which in turn triggers inflammation, oxidative stress, and apoptosis. The objective of this study was to investigate the gene expression of inflammatory, oxidative stress, and apoptotic markers related to endometritis in the uteri of cows. Twenty uterine tissues were collected from the abattoir. Histologically, congestion, edema, hyperemia, and hemorrhagic lesions with massive infiltration of neutrophil and cell necrosis were detected markedly (P < 0.05) in infected uterine samples. Additionally, we identify E. coli using the ybbW gene (177 base pairs; E. coli-specific gene) from infected uterine samples. Moreover, qPCR and western blot results indicated that TLR2, TLR4, proinflammatory mediators, and apoptosis-mediated genes upregulated except Bcl-2, which is antiapoptotic, and there were downregulations of oxidative stress-related genes in the infected uterine tissue. The results of our study suggested that different gene expression regimes related to the immune system reflex were activated in infected uteri. This research gives a novel understanding of active immunological response in bovine endometritis.

A Pilot Study on a Possible Mechanism behind Olfactory Dysfunction in Parkinson's Disease: The Association of TAAR1 Downregulation with Neuronal Loss and Inflammation along Olfactory Pathway.

Parkinson's disease (PD) is characterized not only by motor symptoms but also by non-motor dysfunctions, such as olfactory impairment; the cause is not fully understood. Our study suggests that neuronal loss and inflammation in brain regions along the olfactory pathway, such as the olfactory bulb (OB) and the piriform cortex (PC), may contribute to olfactory dysfunction in PD mice, which might be related to the downregulation of the trace amine-associated receptor 1 (TAAR1) in these areas. In the striatum, although only a decrease in mRNA level, but not in protein level, of TAAR1 was detected, bioinformatic analyses substantiated its correlation with PD. Moreover, we discovered that neuronal death and inflammation in the OB and the PC in PD mice might be regulated by TAAR through the Bcl-2/caspase3 pathway. This manifested as a decrease of anti-apoptotic protein Bcl-2 and an increase of the pro-apoptotic protein cleaved caspase3, or through regulating astrocytes activity, manifested as the increase of TAAR1 in astrocytes, which might lead to the decreased clearance of glutamate and consequent neurotoxicity. In summary, we have identified a possible mechanism to elucidate the olfactory dysfunction in PD, positing neuronal damage and inflammation due to apoptosis and astrocyte activity along the olfactory pathway in conjunction with the downregulation of TAAR1.

A missense mutation in human INSC causes peripheral neuropathy.

PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSCM70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSCM70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2.