Risk of Metachronous Advanced Colorectal Neoplasia After Removal of Diminutive Versus Small Nonadvanced Adenomas: A Multicenter Study.

BACKGROUND: Current postpolypectomy guidelines treat 1-9 mm nonadvanced adenomas (NAAs) as carrying the same level of risk for metachronous advanced colorectal neoplasia (ACRN). AIMS: To evaluate whether small (6-9 mm) NAAs are associated with a greater risk of metachronous ACRN than diminutive (1-5 mm) NAAs. METHODS: We retrospectively evaluated 10,060 index colonoscopies performed from July 2011 to June 2019. A total of 1369 patients aged ≥ 40 years with index NAAs and having follow-up examinations were categorized into 5 groups based on size and number of index findings: Group 1, ≤ 2 diminutive NAAs (n = 655); Group 2, ≤ 2 small NAAs (n = 529); Group 3, 3-4 diminutive NAAs (n = 78); Group 4, 3-4 small NAAs (n = 65); and Group 5, 5-10 NAAs (n = 42). Size was classified based on the largest NAA. ACRN was defined as finding an advanced adenoma or colorectal cancer at follow-up. RESULTS: The absolute risk of metachronous ACRN increased from 7.2% in patients with all diminutive NAAs to 12.2% in patients with at least 1 small NAA (P = 0.002). Patients in Group 2 (adjusted odds ratio [AOR] 1.89; 95% confidence interval [CI], 1.21-2.95), Group 3 (AOR 2.40; 95% CI 1.78-4.90), Group 4 (AOR 2.77; 95% CI 1.35-5.66), and Group 5 (AOR 3.71; 95% CI 1.65-8.37) were associated with an increased risk of metachronous ACRN compared with Group 1. CONCLUSIONS: Patients with small NAAs have an increased risk of metachronous ACRN. Postpolypectomy guidelines should consider including risk stratification between small and diminutive adenomas.

Associations of Three-Dimensional Anthropometric Body Surface Scanning Measurements and Coronary Artery Disease.

Background and Objectives: The relationship between three-dimensional (3D) scanning-derived body surface measurements and biomarkers in patients with coronary artery disease (CAD) were assessed. Methods and Methods: The recruitment of 98 patients with CAD confirmed by cardiac catheterization and 98 non-CAD patients were performed between March 2016 and December 2017. A health questionnaire on basic information, life style variables, and past medical and family history was completed. 3D body surface measurements and biomarkers were obtained. Differences between the two groups were assessed and multivariable analysis performed. Results: It was found that chest width (odds ratio [OR] 0.761, 95% confidence interval [CI] = 0.586-0.987, p = 0.0399), right arm length (OR 0.743, 95% CI = 0.632-0.875, p = 0.0004), waist circumference (OR 1.119, 95% CI = 1.035-1.21, p = 0.0048), leptin (OR 1.443, 95% CI = 1.184-1.76, p = 0.0003), adiponectin (OR 0.978, 95% CI = 0.963-0.994, p = 0.006), and interleukin 6 (OR 1.181, 95% CI = 1.021-1.366, p = 0.0254) were significantly associated with CAD. The combination of biomarker scores and body measurement scores had the greatest area under the curve and best association with CAD (area under the curve of 0.8049 and 95% CI = 0.7440-0.8657). Conclusions: Our study suggests that 3D derived body surface measurements in combination with leptin, adiponectin, and interleukin 6 levels may direct us to those at risk of CAD, allowing a non-invasive approach to identifying high-risk patients.

Combination of Thigh Circumference and Indices of Central Obesity Helps Predict Incident Chronic Kidney Disease: A 14-Year Prospective Cohort Study Using a Three-Dimensional Body Laser Scanner.

OBJECTIVE: Obesity, high body mass index, and visceral fat accumulation are associated with renal diseases. However, the association between body measurements and chronic kidney disease (CKD) is still unclear. METHODS: A cohort of 7,825 participants scheduled for follow-up of CKD was recruited from 2000 to 2008 in Taiwan. A questionnaire was developed to collect the basic demographics, lifestyle variables, personal disease history, and family disease history of the participants. A 3-dimensional body surface scanning system was used to take their body measurements. The participants underwent an average follow-up of 14.3 years for evaluation of the incidence of CKD. A multiple Cox regression model was built. RESULTS: Three body measurements, namely chest width (hazard ratio [HR] 1.059, 95% confidence interval [CI] 1.011-1.110), waist circumference (HR 1.017, 95% CI 1.006-1.029), and thigh circumference (HR 0.941, 95% CI 0.922-0.961), were significantly associated with CKD. Two combinations of body measurements, namely the waist-to-thigh ratio and chest-to-thigh ratio, were derived to predict the occurrence of CKD. Participants with the highest quartile of waist-to-thigh ratio and chest-to-thigh ratio had a 2.175-fold and 2.182-fold risk of developing CKD, respectively. CONCLUSIONS: This study suggests that along with central obesity, body limb measurements can be used as an indicator to predict the occurrence of CKD. The effects of limb measurements on CKD could help provide an innovative perspective regarding the intervention to be developed for the treatment of CKD and a preventive medicine for high-risk individuals. The association of thigh circumference with CKD warrants further investigation.

Octopaminergic neurons have multiple targets in Drosophila larval mushroom body calyx and can modulate behavioral odor discrimination.

Discrimination of sensory signals is essential for an organism to form and retrieve memories of relevance in a given behavioral context. Sensory representations are modified dynamically by changes in behavioral state, facilitating context-dependent selection of behavior, through signals carried by noradrenergic input in mammals, or octopamine (OA) in insects. To understand the circuit mechanisms of this signaling, we characterized the function of two OA neurons, sVUM1 neurons, that originate in the subesophageal zone (SEZ) and target the input region of the memory center, the mushroom body (MB) calyx, in larval Drosophila We found that sVUM1 neurons target multiple neurons, including olfactory projection neurons (PNs), the inhibitory neuron APL, and a pair of extrinsic output neurons, but relatively few mushroom body intrinsic neurons, Kenyon cells. PN terminals carried the OA receptor Oamb, a Drosophila α1-adrenergic receptor ortholog. Using an odor discrimination learning paradigm, we showed that optogenetic activation of OA neurons compromised discrimination of similar odors but not learning ability. Our results suggest that sVUM1 neurons modify odor representations via multiple extrinsic inputs at the sensory input area to the MB olfactory learning circuit.

Hydroxychloroquine might reduce risk of incident endometriosis in patients with systemic lupus erythematosus: A retrospective population-based cohort study.

BACKGROUND: SLE, which is common in women, is commonly treated with HCQ, an anti-inflammation medication. Reproductive-age women with SLE are prone to be impacted by endometriosis. This study analyzes the relationship between HCQ and endometriosis patients with SLE in order to determine whether HCQ is effective for treating the latter. METHODS: This population-based, retrospective cohort study analyzed the SLE risk in a cohort of newly diagnosed SLE patients with endometriosis during 2000 through 2013. Controls were selected at a 1:2 ratio through age-matching using the greedy algorithm. The Cox proportional hazard model was used to analyze the association between HCQ use and endometriosis incidence. Four different Cox regression models were used. Lastly, sensitivity analysis with PSOW and IPW was implemented to evaluate the hazard ratio (HR) of endometriosis after exposure with HCQ. RESULTS: In the cohort where age and sex matched high and low HCQ dosage, the average follow-up time was about 1 year. The cohort's overall incidence rates of endometriosis were 44.54 and 90.03 per 100000 person-month for high and low dosage respectively. The high dose group's conditional hazard ratio (aHR) for incidental endometriosis was 0.482 (CI = 0.191 to 1.213). The incidence rate and Kaplan-Meir curves of endometriosis were consistent with the results for the cohort. CONCLUSION: This study demonstrated that SLE patients continuously treated with HCQ have a lower risk of developing endometriosis. Clinically, HCQ can be beneficial for endometriosis patients with SLE.

Application of Bayesian network and regression method in treatment cost prediction.

Charging according to disease is an important way to effectively promote the reform of medical insurance mechanism, reasonably allocate medical resources and reduce the burden of patients, and it is also an important direction of medical development at home and abroad. The cost forecast of single disease can not only find the potential influence and driving factors, but also estimate the active cost, and tell the management and reasonable allocation of medical resources. In this paper, a method of Bayesian network combined with regression analysis is proposed to predict the cost of treatment based on the patient's electronic medical record when the amount of data is small. Firstly, a set of text-based medical record data conversion method is established, and in the clustering method, the missing value interpolation is carried out by weighted method according to the distance, which completes the data preparation and processing for the realization of data prediction. Then, aiming at the problem of low prediction accuracy of traditional regression model, this paper establishes a prediction model combined with local weight regression method after Bayesian network interpretation and classification of patients' treatment process. Finally, the model is verified with the medical record data provided by the hospital, and the results show that the model has higher prediction accuracy.

Long term outcomes of colon polyps with high grade dysplasia following endoscopic resection.

BACKGROUND: The risk of recurrent colonic adenoma associated with high-grade dysplasia (HGD) colon polyps at baseline colonoscopy remains unclear. We conducted a clinical cohort study with patients who underwent polypectomy during screen colonoscopy to assess recurrent colonic adenoma risk factors. METHODS: 11,565 patients at our facility underwent screen colonoscopy between September 1998 and August 2007. Data from patients with HGD colon polyps who had undergone follow-up colonoscopy were included for analysis. RESULTS: Data from 211 patients was included. Rates of metachronous adenoma and advanced adenoma at follow-up were 58% and 20%, respectively. Mean follow-up period was 5.5 ± 1.8 (3-12) years. Univariate logistic regression analysis revealed that an adenoma count of ≥ 3 at baseline colonoscopy was strongly associated with overall recurrence, multiple recurrence, advanced recurrence, proximal recurrence, and distal adenoma recurrence with odds ratios of 4.32 (2.06-9.04 95% CI), 3.47 (1.67-7.22 95% CI), 2.55 (1.11-5.89 95% CI), 2.46 (1.16-5.22 95% CI), 2.89 (1.44-5.78 95% CI), respectively. Multivariate analysis revealed gender (male) [P = 0.010; OR 3.09(1.32-7.25 95% CI)] and adenoma count ≥ 3 [P = 0.002; OR 3.08(1.52-6.24 95% CI)] at index colonoscopy to be significantly associated with recurrence of advanced adenoma. CONCLUSION: Recurrence of colonic adenoma at time of follow-up colonoscopy is common in patients who undergo polypectomy for HGD colon adenomas during baseline colonoscopy. Risk of further developing advanced adenomas is associated with gender and the number of colon adenomas present.

Optimal procedural sequence for same-day bidirectional endoscopy with moderate sedation: A prospective randomized study.

BACKGROUND AND AIM: Same-day bidirectional endoscopy (BDE) is a commonly performed procedure, but the optimal sequence for the procedure with moderate conscious sedation is not well established. This study investigated the optimal sequence for same-day BDE under moderate conscious sedation and carbon dioxide insufflation in terms of sedation doses, patient discomfort, and colonoscopy performance. METHODS: A prospective randomized controlled study of 120 patients who were scheduled for BDE examination was performed. Colonoscopy followed by esophagogastroduodenoscopy (EGD) examination was performed in 60 patients (colonoscopy-EGD group), and EGD followed by colonoscopy examination was performed in another 60 patients (EGD-colonoscopy group). Endoscopists and patients completed a questionnaire to assess objective and subjective discomfort. RESULTS: Baseline demographics, procedure indications, bowel preparation quality, cecal intubation rate/time, colonoscopy withdrawal time, endoscopic interventions, BDE procedure time, colon polyp/adenoma detection rates, patient discomfort, and adverse events were similar between the two study groups. The total doses of fentanyl and midazolam were significantly higher for the colonoscopy-EGD group than for the EGD-colonoscopy group (83.4 ± 17.7 vs 68.7 ± 18.6 µg and 6.3 ± 1.4 vs 5.2 ± 1.3 mg, P < 0.0001 and P < 0.0001, respectively). The recovery time to discharge was significantly longer for the colonoscopy-EGD group than for the EGD-colonoscopy group (43.5 ± 16.2 vs 34.5 ± 8.9 min, P = 0.0003). CONCLUSIONS: Esophagogastroduodenoscopy followed by colonoscopy is the optimal sequence for same-day BDE under moderate conscious sedation and carbon dioxide insufflation. Following this order allows for a reduction of sedation doses and for shorter recovery times.

Analyzing the influence of gastric intestinal metaplasia on gastric ulcer healing in Helicobacter pylori-infected patients without atrophic gastritis.

BACKGROUND: Gastric epithelial hyper-proliferation was reported in patients with Helicobacter pylori (H. pylori)-infected gastric mucosa with intestinal metaplasia (IM) changes. In patients with gastric ulcer (GU) and IM, the GU may have a different healing rate in comparison to patients without IM. This study aimed to compare the difference in GU healing between H. pylori-infected patients with IM and those without IM. METHODS: We retrospectively analyzed patients at the Keelung Chung Gung Memorial Hospital during the period from March 2005 to January 2011. The inclusion criteria were: 1) endoscopic findings of GU and biopsy histological examination plus rapid urease test indicating H. pylori infection; 2) gastric IM adjacent to a GU but with no atrophic gastritis changes; 3) patients receiving H. pylori eradication triple therapy and 8 weeks of maintenance therapy with a proton pump inhibitor; and 4) patients receiving follow-up endoscopy within the 3rd and the 4th months after treatment. RESULTS: In total, 327 patients with GU and H. pylori infection (136 with IM and 191 without IM) were included. Patients with IM had a higher GU healing rate than those without IM (91.9% vs. 84.3%, P = 0.040). Multivariate logistical regression analysis revealed that failure of H. pylori eradication (Odds = 4.013, 95% CI: 1.840-8.951, P < 0.001) and gastric IM (Odds = 0.369, 95% CI: 0.168-0.812, P = 0.013) were the predictors of non-healing GU following treatment. CONCLUSIONS: Patient with gastric IM change may have a higher GU healing rate than those without gastric IM. However, successful H. pylori eradication is a more important factor for GU healing than gastric IM.

Carbon dioxide insufflation during colonoscopy can significantly decrease post-interventional abdominal discomfort in deeply sedated patients: A prospective, randomized, double-blinded, controlled trial.

BACKGROUND AND AIM: CO2 has been reported to be absorbed from the bowel more rapidly than air, resulting in a discomfort reduction after colonoscopy. Its role in deeply sedated patients is limited. This study was designed to investigate the efficacy and safety of CO2 insufflation during colonoscopy in patients deeply sedated with propofol. METHODS: A total of 125 continuous patients were randomly assigned to receive either CO2 (n = 63) or air (n = 62) insufflation during propofol-sedated colonoscopy. Postcolonoscopy abdominal pain, distention, and satisfaction were assessed at 1, 3, and 24 h after the procedure, and the proportions of pain-free and distention-free patients were compared. Residual bowel gas in the colon and small bowel was evaluated at 1 h after colonoscopy. End-tidal CO2 and O2 saturation was measured for safety analysis. RESULTS: There was a significant difference between the two groups regarding the postcolonoscopy abdominal pain, distention, and subjective satisfaction at 1 h (P < 0.001) and 3 h (P < 0.01) after the procedure. Patients' pain and distention at 1 and 3 h after the procedure were significantly lower in the CO2 group (P < 0.01). Residual bowel gas in the colon and small bowel was significantly less in the CO2 group (P < 0.001). There was no significant difference in end-tidal CO2 levels between two groups before, during, and after the procedure. CONCLUSIONS: Compared with air, CO2 insufflation during colonoscopy reduced postcolonoscopy abdominal discomfort and improved patients' satisfaction. It was safe to use CO2 insufflation in deeply sedated colonoscopy.

Treatment-emergent depression and anxiety between peginterferon alpha-2a versus alpha-2b plus ribavirin for chronic hepatitis C.

BACKGROUND: This study investigates differences in depression and anxiety between patients with chronic hepatitis C who are treated with peginterferon alpha-2a (PegIFN-α-2a) plus ribavirin and those who are treated with peginterferon alpha-2b (PegIFN-α-2b) plus ribavirin. METHODS: In this 24 week, non-randomized, observational, prospective study, 55 patients with chronic hepatitis C were treated with PegIFN-α-2a plus ribavirin (Group 1), and 26 patients were treated with PegIFN-α-2b plus ribavirin (Group 2). All patients underwent assessment using the Hospital Anxiety and Depression Scale (HADS) at the baseline and at weeks 4, 12 and 24. Patients with depression scores (HADS-D) ≥ 8 and anxiety scores (HADS-A) ≥ 8 were defined as having depression and anxiety, respectively. The factors that were associated with depression and anxiety during the 24 week antiviral treatment were determined. RESULTS: During the 24 week antiviral treatment, the proportion of patients with depression significantly increased over time in both groups (Group 1: p = 0.048; Group 2: p = 0.044). The proportion of patients with anxiety did not significantly change during the follow-up period in either group. Incidences of depression or anxiety did not differ significantly between Group 1 and Group 2. A history of alcohol use disorder was an independent predictor of depression at week 12 (p < 0.001) and week 24 (p < 0.001), and a poor virological response to treatment was associated with depression at week 24 (p = 0.029). Patients who had more physical comorbidities were more likely to suffer from anxiety at week 12 (p = 0.038). CONCLUSIONS: This study did not identify significant differences in depression or anxiety between in patients with chronic hepatitis C who underwent a 24 week antiviral treatment regimen with PegIFN-α-2a plus ribavirin and those who underwent a regiment with PegIFN-α-2b plus ribavirin. Future research with larger samples and a randomized, controlled design are required to verify the findings in this study. TRIAL REGISTRATION: This clinical study has been registered at ClinicalTrials.gov. (Trial registration: NCT02943330 ).

Programming memristor arrays with arbitrarily high precision for analog computing.

In-memory computing represents an effective method for modeling complex physical systems that are typically challenging for conventional computing architectures but has been hindered by issues such as reading noise and writing variability that restrict scalability, accuracy, and precision in high-performance computations. We propose and demonstrate a circuit architecture and programming protocol that converts the analog computing result to digital at the last step and enables low-precision analog devices to perform high-precision computing. We use a weighted sum of multiple devices to represent one number, in which subsequently programmed devices are used to compensate for preceding programming errors. With a memristor system-on-chip, we experimentally demonstrate high-precision solutions for multiple scientific computing tasks while maintaining a substantial power efficiency advantage over conventional digital approaches.

Waist-to-height ratio for the prediction of gallstone disease among different obesity indicators.

Background: Factors of metabolic syndrome such as obesity are well-known risk factors for gallstone disease (GSD). There are different indicators of obesity, including weight, body mass index, waist circumference, and waist-to-height ratio. The predictive ability of different obesity indicators for GSD remains unclear. Objective: To explore the most efficient predictor of GSD among the different anthropometric indicators of obesity. Methods: This population-based cross-sectional study included 2263 participants who completed a questionnaire detailing their demographics, medical history, and lifestyle between 2014 and 2017 in Taiwan. Blood samples were collected and physical examinations, including anthropometric measurements, were performed. Gallstone disease was ascertained using ultrasonography. Multivariate analyses were performed to identify independent risk factors for GSD. Results: The overall prevalence of GSD was 8.8%. According to the multivariate analysis, individuals with a waist-to-height ratio ≥0.5 (odds ratio|odds ratios (OR) = 1.65, 95% confidence interval (CI) = 1.10-2.48, p = 0.017) had an increased risk of GSD. Diabetes was the main risk factor for GSD in men (OR = 2.06, 95% CI = 1.17-3.65, p = 0.013). Among women, waist-to-height ratio >0.5 (OR = 1.76, 95% CI = 1.03-3.02, p = 0.040) and current hormone drug use (OR = 2.73, 95% CI = 1.09-6.84, p = 0.033) were significant risk factors for gallstones. Conclusion: GSD was independently associated with central obesity and exogenous hormone intake in women. Among the anthropometric indicators used to assess central obesity, waist-to-height ratio was the most accurate predictor of GSD.

Supplementation of Dietary Quercetin and Vitamin E Promotes the Intestinal Structure and Immune Barrier Integrity in Aged Breeder Hens.

In aged animals, the physiological functions of the gastrointestinal tract (GIT) are reduced. Dietary intervention is necessary to re-activate GIT functions. The objective of this study was to investigate the impacts of dietary combination of quercetin (Q) and vitamin E (VE) on the intestinal structure and barrier integrity in aged breeder chickens. A sum of 400 (65-wks-old) Tianfu breeder hens were randomly allotted into four (4) groups with four (4) replicates, and fed with basal diet; basal diet supplemented with 0.4g/kg of Q; basal diet supplemented with 0.2g/kg of VE; and basal diet supplemented with the combination of Q (0.4 g/kg) and VE (0.2 g/kg) for 14 weeks. At the end of the 14th week, serum and gut segments were collected from eight hens per group for analyses. The results showed that Q+VE exerted synergistic effects on intestinal morphology by promoting villi height and crypt depth (P < 0.05), as well as mitigated the intestinal inflammatory damage of the aged hens, but decreased the concentration of serum D-lactate and diamine oxidase; and increased the levels of secretory immunoglobulin A (sIgA) and Mucin-2 mRNA (P < 0.05). Furthermore, the mRNA expression of intestinal tight junction proteins including occludin, ZO1, and claudin-1 was increased by Q+VE (P < 0.05). Moreover, Q+VE decreased the mRNA expression of the pro-inflammatory genes (TNF-α, IL-6, and IL-1ß), and increased the expression of anti-inflammatory genes (IL-10 and IL-4) (P < 0.05). These results were consistent with the mRNA expression of Bax and Bcl-2. In addition, Q+VE protected the small intestinal tract from oxidative damage by increasing the levels of superoxide dismutase, total antioxidant capacity, glutathione peroxidase, catalase (P < 0.05), and the mRNA expression of SOD1 and GPx-2. However, Q+VE decreased malondialdehyde levels in the intestine compared to the control (P < 0.05). These results indicated that dietary Q+VE improved intestinal function in aged breeder hens, by protecting the intestinal structure and integrity. Therefore, Q+VE could act as an anti-aging agent to elevate the physiological functions of the small intestine in chickens.

Higher Leptin-to-Adiponectin Ratio Strengthens the Association Between Body Measurements and Occurrence of Type 2 Diabetes Mellitus.

Aim: This case-control study aimed to investigate the interrelations of body measurements and selected biomarkers in type 2 diabetes mellitus (T2DM). Methods: We recruited 98 patients with T2DM and 98 controls from 2016 to 2018 in Taiwan. Body measurements were obtained using a three-dimensional body surface scanning system. Four biomarkers related to insulin resistance, adipokines, and inflammation were assayed. A multiple logistic regression model was used to perform multivariable analyses. Results: Four body measurements, namely waist circumference (odds ratio, OR = 1.073; 95% confidence interval, CI = 1.017-1.133), forearm circumference (OR = 1.227; 95% CI = 1.002-1.501), thigh circumference (OR = 0.841; 95% CI = 0.73-0.969), and calf circumference (OR = 1.25; 95% CI = 1.076-1.451), were significantly associated with T2DM. Leptin (OR = 1.09; 95% CI = 1.036-1.146) and adiponectin (OR = 0.982; 95% CI = 0.967-0.997) were significantly associated with T2DM. Six body measurement combinations, namely body mass index, waist-to-hip ratio, waist-to-height ratio, waist-to-thigh ratio, forearm-to-thigh ratio, and calf-to-thigh ratio (CTR), were significantly associated with T2DM. CTR had the strongest linear association with T2DM. Moderating effects of significant biomarkers, namely leptin and adiponectin, were observed. Participants with high leptin-to-adiponectin ratios and in the fourth CTR quartile were 162.2 times more prone to develop T2DM. Conclusions: We concluded that a combination of leptin and adiponectin modulated the strength of the association between body measurements and T2DM while providing clues for high-risk group identification and mechanistic conjectures of preventing T2DM.

Adverse body measurements are superior to sarcopenia-associated measurements in predicting chronic diseases.

Few studies have demonstrated an association of sarcopenia-associated body measurements with chronic diseases through a comprehensive methodology. This study aims to examine the relationship between sarcopenia-associated body measurements and chronic diseases. This is a cohort study. We recruited 316 community dwellers, including 76 patients with sarcopenia and 240 controls, and obtained their body measurements associated with sarcopenia. We collected three-dimensional anthropometric body-surface measurements from 11,158 participants during 2000-2008 and followed up this cohort for 15 years to examine the association of these measurements with the risk of chronic diseases such as hypertension, type 2 diabetes mellitus (T2DM), heart disease, and nephrotic syndrome. Univariate analysis, canonical correlation, and Cox regression analysis were performed to explore the associations. Decreased waist width, upper left arm circumference, and left thigh circumference were significantly associated with sarcopenia. The adverse body measure score (ABMS) was derived by combining significant measurements, namely left upper arm circumference, waist width, and left thigh circumference, and used to predict the risk of hypertension, T2DM, heart diseases, and nephrotic syndrome. A positive association was observed between the ABMS and chronic diseases. Considering the first quartile of the ABMS as a reference, we determined hazard ratios of 2.259, 2.495, 1.332, and 1.595 for hypertension, T2DM, heart disease, and nephrotic syndrome, respectively, in the fourth quartile. Chronic diseases were more strongly associated with the ABMS than with sarcopenia-related body measurements alone. A high ABMS, which includes higher upper arm circumference, higher waist width, and lower thigh circumference, can significantly predict chronic diseases.

Bacterial type II toxin-antitoxin systems acting through post-translational modifications.

The post-translational modification (PTM) serves as an important molecular switch mechanism to modulate diverse biological functions in response to specific cues. Though more commonly found in eukaryotic cells, many PTMs have been identified and characterized in bacteria over the past decade, highlighting the importance of PTMs in regulating bacterial physiology. Several bacterial PTM enzymes have been characterized to function as the toxin component of type II TA systems, which consist of a toxin that inhibits cell growth and an antitoxin that protects the cell from poisoning by the toxin. While TA systems can be classified into seven types based on nature of the antitoxin and its activity, type II TA systems are perhaps the most studied among the different TA types and widely distributed in eubacteria and archaea. The type II toxins possessing PTM activities typically modify various cellular targets mostly associated with protein translation and DNA replication. This review mainly focuses on the enzymatic activities, target specificities, antitoxin neutralizing mechanisms of the different families of PTM toxins. We also proposed that TA systems can be conceptually viewed as molecular switches where the 'on' and 'off' state of the system is tightly controlled by antitoxins and discussed the perspective on toxins having other physiologically roles apart from growth inhibition by acting on the nonessential cellular targets.

Reconfigurable Stochastic neurons based on tin oxide/MoS2 hetero-memristors for simulated annealing and the Boltzmann machine.

Neuromorphic hardware implementation of Boltzmann Machine using a network of stochastic neurons can allow non-deterministic polynomial-time (NP) hard combinatorial optimization problems to be efficiently solved. Efficient implementation of such Boltzmann Machine with simulated annealing desires the statistical parameters of the stochastic neurons to be dynamically tunable, however, there has been limited research on stochastic semiconductor devices with controllable statistical distributions. Here, we demonstrate a reconfigurable tin oxide (SnOx)/molybdenum disulfide (MoS2) heterogeneous memristive device that can realize tunable stochastic dynamics in its output sampling characteristics. The device can sample exponential-class sigmoidal distributions analogous to the Fermi-Dirac distribution of physical systems with quantitatively defined tunable "temperature" effect. A BM composed of these tunable stochastic neuron devices, which can enable simulated annealing with designed "cooling" strategies, is conducted to solve the MAX-SAT, a representative in NP-hard combinatorial optimization problems. Quantitative insights into the effect of different "cooling" strategies on improving the BM optimization process efficiency are also provided.

Proteomic analysis reveals the mechanism of different environmental stress-induced tolerance of Pseudomonas aeruginosa to monochloramine disinfection.

Although drinking water disinfection proved to be an effective strategy to eliminate many pathogens, bacteria can still show disinfection tolerance in drinking water distribution systems. To date, the molecular mechanisms on how environmental stress affects the tolerance of Pseudomonas aeruginosa to monochloramine are not well understood. Here, we investigated how three stress conditions, namely starvation, low temperature, and starvation combined with low temperature, affected the monochloramine tolerance of Pseudomonas aeruginosa, an opportunistic pathogen commonly found in drinking water distribution systems. All stress conditions significantly promoted monochloramine tolerance, among which starvation had the most drastic effects. Proteomic analyses suggested that the three conditions not only triggered a positive antioxidant defense against oxidative damages but also prepared the bacteria to employ a passive defense mechanism against disinfectants via dormancy. Moreover, the expression of antioxidant enzymes reached the maximum under the starvation condition and further low temperature treatment had little effect on bacterial response to oxidative stress. Instead, we found further treatment of the starved cells with low temperature decreased the osmotic stress response and the stringent response, which generally play pivotal roles in disinfection tolerance. Taken together, these findings shed light on how abiotic factors influence the bacterial disinfection tolerance and will aid design of efficient strategies to eliminate Pseudomonas aeruginosa from drinking water.

Investigation of the Genome-Wide Genetic and Epigenetic Networks for Drug Discovery Based on Systems Biology Approaches in Colorectal Cancer.

Colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide. The mechanisms leading to the progression of CRC are involved in both genetic and epigenetic regulations. In this study, we applied systems biology methods to identify potential biomarkers and conduct drug discovery in a computational approach. Using big database mining, we constructed a candidate protein-protein interaction network and a candidate gene regulatory network, combining them into a genome-wide genetic and epigenetic network (GWGEN). With the assistance of system identification and model selection approaches, we obtain real GWGENs for early-stage, mid-stage, and late-stage CRC. Subsequently, we extracted core GWGENs for each stage of CRC from their real GWGENs through a principal network projection method, and projected them to the Kyoto Encyclopedia of Genes and Genomes pathways for further analysis. Finally, we compared these core pathways resulting in different molecular mechanisms in each stage of CRC and identified carcinogenic biomarkers for the design of multiple-molecule drugs to prevent the progression of CRC. Based on the identified gene expression signatures, we suggested potential compounds combined with known CRC drugs to prevent the progression of CRC with querying Connectivity Map (CMap).