High prevalence of erectile dysfunction in men with hyperthyroidism: a meta-analysis.

OBJECTIVE: The objective of this study was to evaluate the association between hyperthyroidism and the risk of developing erectile dysfunction (ED). METHODS: A comprehensive search of multiple databases, including PubMed, Embase, Cochrane, and Web of Science, was conducted to identify relevant studies investigating the relationship between hyperthyroidism and ED in men. The quality of the included studies was assessed using the Newcastle‒Ottawa Quality Rating Scale, and a meta-analysis was performed using Stata 16.0 and RevMan 5.3 software. RESULTS: A total of four papers encompassing 25,519 study subjects were included in the analysis. Among these, 6,429 individuals had hyperthyroidism, while 19,090 served as controls. The overall prevalence of ED in patients with hyperthyroidism was determined to be 31.1% (95% CI 0.06-0.56). In patients with uncomplicated hyperthyroidism, the incidence of ED was 21.9% (95% CI 0.05-0.38). The combined odds ratio (OR) for the four studies was 1.73 (OR: 1.73; 95% CI [1.46-2.04]; p < .00001). CONCLUSION: Our findings demonstrate a higher incidence of ED in patients with hyperthyroidism. These results provide valuable information for healthcare professionals and can facilitate discussions surrounding appropriate treatment options for ED in patients with hyperthyroidism.

Transcriptional reprogramming restores UBE3A brain-wide and rescues behavioral phenotypes in an Angelman syndrome mouse model.

Angelman syndrome (AS) is a neurogenetic disorder caused by the loss of ubiquitin ligase E3A (UBE3A) gene expression in the brain. The UBE3A gene is paternally imprinted in brain neurons. Clinical features of AS are primarily due to the loss of maternally expressed UBE3A in the brain. A healthy copy of paternal UBE3A is present in the brain but is silenced by a long non-coding antisense transcript (UBE3A-ATS). Here, we demonstrate that an artificial transcription factor (ATF-S1K) can silence Ube3a-ATS in an adult mouse model of Angelman syndrome (AS) and restore endogenous physiological expression of paternal Ube3a. A single injection of adeno-associated virus (AAV) expressing ATF-S1K (AAV-S1K) into the tail vein enabled whole-brain transduction and restored UBE3A protein in neurons to ∼25% of wild-type protein. The ATF-S1K treatment was highly specific to the target site with no detectable inflammatory response 5 weeks after AAV-S1K administration. AAV-S1K treatment of AS mice showed behavioral rescue in exploratory locomotion, a task involving gross and fine motor abilities, similar to low ambulation and velocity in AS patients. The specificity and tolerability of a single injection of AAV-S1K therapy for AS demonstrate the use of ATFs as a promising translational approach for AS.

Feature impact assessment: a new score to identify relevant metabolomics features in artificial neural networks using validated labels.

INTRODUCTION: Artificial Neural Networks (ANN) are increasingly used in metabolomics but are hard to interpret. OBJECTIVES: We aimed at developing a feature impact score that is model-agnostic, simple, and interpretable. METHODS: Feature Impact Assessment (FIA) is calculated by varying combinations of features within their observed value range and checking for changes in prediction outcomes. FIA was implemented in R and tested on metabolomics datasets. RESULTS: FIA exceeded LIME and SHAP in selecting biologically meaningful features. Values were comparable across different ANN architectures. CONCLUSION: FIA is a novel score ranking feature impact, helping interpreting ANN in the metabolomics field.

Heterogeneity of vulnerability and taste changes in older cancer patients undergoing chemotherapy: a latent class analysis.

PURPOSE: Taste changes and vulnerability are commonly co-occurring in oncology patients undergoing chemotherapy. However, few studies explored the association and the inter-individual variability of these two conditions. This study aimed to identify heterogeneous subtypes of vulnerability and taste changes in older cancer patients undergoing chemotherapy, and explore individuals' characteristics and risk factors. METHODS: In this cross-sectional study, the latent class analysis (LCA) was conducted to identify the heterogeneous subgroups of patients with distinct vulnerability and taste change profiles. Differences in sociodemographic and clinical characteristics among the subpopulation were evaluated using parametric and nonparametric tests. Multinomial logistic regression was performed to investigate predictors of taste change-vulnerability subgroup classification. RESULTS: Three subgroups of those older cancer survivors were identified from the LCA: Class 1 (27.5%)-"Moderate taste change and low vulnerability", Class 2 (29.0%)-"Low taste change and moderate vulnerability", Class 3 (43.5%)-"High taste change and high vulnerability". 98.9% of Class 3 reported taste changes and 54.0% reported vulnerability. Results from multinomial logistic regression indicated that patients in Class 3 were more likely to report experiencing mouth dryness and high blood pressure, and have received more than 3 cycles of chemotherapy. CONCLUSION: The findings could provide new insights into the association between taste changes and vulnerability in older cancer adults receiving chemotherapy. Identifying different latent classes of taste changes and vulnerability would be helpful for developing interventions tailored to the heterogeneous survivors.

Phage based electrochemical detection of Escherichia coli in drinking water using affinity reporter probes.

The monitoring of drinking water for indicators of fecal contamination is crucial for ensuring a safe supply. In this study, a novel electrochemical method was developed for the rapid and sensitive detection of Escherichia coli (E. coli) in drinking water. This strategy is based on the use of engineered bacteriophages (phages) to separate and concentrate target E. coli when conjugated with magnetic beads, and to facilitate the detection by expressing gold binding peptides fused alkaline phosphatase (GBPs-ALP). The fusion protein GBPs-ALP has both the enzymatic activity and the ability to directly bind onto a gold surface. This binding-peptide mediated immobilization method provided a novel and simple approach to immobilize proteins on a solid surface, requiring no post-translational modifications. The concentration of E. coli was determined by measuring the activity of the ALP on gold electrodes electrochemically using linear sweep voltammetry (LSV). This approach was successfully applied in the detection of E. coli in drinking water. We were able to detect 105 CFU mL-1 of E. coli within 4 hours. After 9 hours of preincubation, 1 CFU of E. coli in 100 mL of drinking water was detected with a total assay time of 12 hours. This approach compares favorably to the current EPA method and has the potential to be applied to detect different bacteria in other food matrices.

In Vitro Generation of Anti-Osteosarcoma Cytotoxic Activity Using Dendritic Cells Loaded with Heat Shock Protein 70-Peptide Complexes.

Introduction: This study aimed at evaluating the anti-osteosarcoma activity of cytotoxic T lymphocytes (CTLs) induced by dendritic cells (DCs) pulsed with heat shock protein 70-peptide complexes (Hsp70-PCs). Materials and methods: Human recombinant Hsp70 expression was analyzed using thin layer scanning and Western blot assay. Tumor antigens from Saos-2 cells were extracted to reconstitute Hsp70-PCs. Maturation of cord blood-derived DC was evaluated by alkaline phosphatase-anti-alkaline phosphatase kit and inverted microscope. The anti-osteosarcoma activity of CTLs evoked by DCs loaded with Hsp70-PCs was determined using Thiazolyl Blue Tetrazolium Bromide (MTT) assay. Results: Hsp70 protein level in BL21 (DE3) increased in a time-dependent manner after induction. The expression of surface markers was upregulated and a typical dendritic morphology was observed in mature DCs. Allogeneic CTLs exhibited strong cytotoxic activity against Saos-2 cells. Conclusion: Our in vitro experiment demonstrated the potent induction of cytotoxic activity against osteosarcoma using DC-based vaccine loaded with Hsp70-PCs.

Electrochemical Detection of Escherichia coli from Aqueous Samples Using Engineered Phages.

In this study, an enzyme-based electrochemical method was developed for the detection of Escherichia coli (E. coli) using the T7 bacteriophages engineered with lacZ operon encoding for beta-galactosidase (ß-gal). The T7lacZ phages can infect E. coli, and have the ability to trigger the overexpression of ß-gal during the infection of E. coli. The use of the engineered phages resulted in a more sensitive detection of E. coli by (1) overexpression of ß-gal in E. coli during the specific infection and (2) release of the endogenous intracellular ß-gal from E. coli following infection. The endogenous and phage-induced ß-gal was detected using the electrochemical method with 4-aminophenyl-ß-galactopyranoside (PAPG) as a substrate. The ß-gal catalyzed PAPG to an electroactive species p-aminophenol (PAP) which could be monitored on an electrode. The electrochemical signal was proportional to the concentration of E. coli in the original sample. We demonstrated the application of our strategy in aqueous samples (drinking water, apple juice, and skim milk). Using this method, we were able to detect E. coli at the concentration of approximately 105 CFU/mL in these aqueous samples in 3 h and 102 CFU/mL after 7 h. This strategy has the potential to be extended to detect different bacteria using specific bacteriophages engineered with gene encoding for appropriate enzymes.

Development of a novel bacteriophage based biomagnetic separation method as an aid for sensitive detection of viable Escherichia coli.

The application of bacteriophage combined with the use of magnetic separation techniques has emerged as a valuable tool for the sensitive identification and detection of bacteria. In this study, bacteriophage T7 labelled magnetic beads were developed for the detection of viable bacterial cells. Fusion of the biotin acceptor peptide (BAP) with the phage capsid protein gene and the insertion of the biotin ligase (BirA) gene enabled the display of the BAP ligand and the expression protein BirA during the replication cycle of phage infection. The replicated Escherichia coli specific bacteriophage was biotinylated in vivo and coated on magnetic beads via streptavidin-biotin interaction. Immobilization efficiency of the recombinant phage was investigated on magnetic beads and the phage-bead complex was evaluated by detecting E. coli from inoculated broth. When compared to the wild type phage, the recombinant phage T7birA-bap had a high immobilization density on streptavidin-coated magnetic beads and could capture 86.2% of E. coli cells from broth within 20 min. As this phage-based biomagnetic detection approach provided a low detection limit of 10(2) CFU mL(-1) without pre-enrichment, we believe this assay could be further developed to detect other bacteria of interest by applying host-specific phages. This would be of particular use in detecting bacteria which are difficult to grow or replicate slowly in culture.

Rapid screening of waterborne pathogens using phage-mediated separation coupled with real-time PCR detection.

Escherichia coli O157:H7 is a ubiquitous pathogen which can be linked to foodborne outbreaks worldwide. In addition to the significant illnesses, hospitalizations, and deaths resulting from the outbreaks, there can be severe economic consequences to farmers, food manufacturers, and municipalities. A rapid detection assay which can validate sanitation and water quality would prove beneficial to these situations. Here, we report a novel bacteriophage-mediated detection of E. coli O157:H7 which utilizes the specific recognition between phages and their host cell as well as the natural lysis component of the infection cycle for DNA release. Carboxylic acid-functionalized magnetic beads were conjugated with bacteriophage and used to separate and concentrate E. coli O157:H7. The effects of bead incubation time, salinity, pH, and temperature on the bio-magnetic separation were investigated and compared to an antibody-based counterpart. The conditions of 0.01 M PBS, pH 7.0, and 20 min of reaction at 37 °C were found to be optimal. The capture efficiency of the coupled assay was approximately 20 % higher than that of antibody-based separation under extreme conditions. The resulting bead-phage-bacteria complexes were quantitatively detected by real-time PCR (qPCR). Our results demonstrated that the use of phage-based magnetic separation coupled with qPCR improved the sensitivity of detection by 2 orders of magnitude compared that without phage-based pre-concentration. Specificity and selectivity of the assay system was evaluated, and no cross-reactivity occurred when Salmonella typhimurium, Staphylococcus aureus, and Pseudomonas aeruginosa were tested. The total assay time was less than 2 h.

Associations among frailty status, hypertension, and fall risk in community-dwelling older adults.

Objectives: Frailty and hypertension often coexist in older adults, which may lead to fall risks. This study aimed to examine the relationship between frailty status, hypertension, and fall risk. Methods: In this cross-sectional study, a total of 401 older adults were conveniently recruited from communities in Wuxi, China, between September 2022 and November 2022. The fall risk self-assessment checklist from the Stopping Elderly Accidents, Deaths & Injuries (STEADI) Toolkit was used to evaluate their fall risks. The FRAIL scale questionnaire was used to assess frailty status. Participants' demographic information and comorbidities were collected. Multivariate logistic regression, generalized additive model, and smooth curve fitting were used to analyze the association between frailty, hypertension, and fall risk. Results: Frailty had a strong association with increased prevalence of fall risk among the participants (OR 8.52, 95% CI 3.21-22.57; P < 0.001). Hypertension significantly increased the fall risk among older adults (OR 1.87, 95% CI 1.11-3.13; P = 0.019). The group with hypertension and frailty had the highest prevalence of fall risk (OR 12.24, 95% CI 3.51-42.65). Smooth curve fitting showed a nonlinear association between frailty and fall risk in hypertension status. In the progress of pre-frailty to frailty status, a higher tendency to fall was found among older adults with hypertension. Conclusions: Frailty status and hypertension independently and jointly influenced the increased prevalence of fall risk. Enhanced frailty and hypertension management may help decrease fall risk among this population.

The association between inflammation-related biomarkers and the subtypes of cancer-related cognitive impairment in colorectal cancer patients: A latent profile analysis.

PURPOSE: Cancer-related cognitive impairment (CRCI) has garnered considerable attention, yet limited research has delved into nuanced distinctions among varying degrees of CRCI in colorectal cancer survivors. This study aimed to identify distinct subgroups based on the patterns of CRCI, assess the heterogeneity among different subgroups, and investigate the potential correlations between the subgroups of CRCI and inflammation-related biomarkers. METHODS: 268 colorectal cancer patients were enrolled in this cross-sectional study, followed by the Functional Assessment of Cancer Therapy-Cognitive Function. The determination of CRCI subgroups was accomplished by the latent profile analysis (LPA). The effects of inflammation-related biomarkers on CRCI were examined using the binary logistic regression analysis. The receiver operating characteristic (ROC) curves assessed the diagnostic efficacy of inflammation-related biomarkers. RESULTS: Two latent profiles were identified: CRCI (n = 64, 23.88%) and non-CRCI (n = 204, 76.12%). Independent factors for CRCI in colorectal cancer patients were SIRI (OR = 3.248, 95%CI [1.197-8.807], P = 0.021) and ALI (OR = 0.962, 95%CI [0.937-0.989], P = 0.005). The areas under the curve (AUCs) for SIRI and ALI in predicting CRCI were 0.781 and 0.774, with the optimal cut-off values being 0.70 and 37.04, respectively. CONCLUSIONS: Colorectal cancer patients exhibited divergent cognitive performance profiles, categorized into two subgroups based on LPA. SIRI and ALI were identified as independent factors for CRCI, demonstrating strong diagnostic accuracy. These two inflammation-related biomarkers may potentially be novel indicators to identify and manage the development of CRCI among colorectal cancer patients.

Recent advances of Raman spectroscopy for the analysis of bacteria.

Rapid and sensitive bacteria detection and identification are becoming increasingly important for a wide range of areas including the control of food safety, the prevention of infectious diseases, and environmental monitoring. Raman spectroscopy is an emerging technology which provides comprehensive information for the analysis of bacteria in a short time and with high sensitivity. Raman spectroscopy offers many advantages including relatively simple operation, non-destructive analysis, and information on molecular differences between bacteria species and strains. A variety of biochemical properties can be measured in a single spectrum. This short review covers the recent advancements and applications of Raman spectroscopy for bacteria analysis with specific focuses on bacteria detection, bacteria identification and discrimination, as well as bacteria antibiotic susceptibility testing in 2022. The development of novel substrates, the combination with other techniques, and the utilization of advanced data processing tools for the improvement of Raman spectroscopy and future directions are discussed.

Effects of syllable boundaries in Tibetan reading.

Interword spaces exist in the texts of many languages that use alphabetic writing systems. In most cases, interword spaces, as a kind of word boundary information, play an important role in the reading process of readers. Tibetan also uses alphabetic writing, its text has no spaces between words as word boundary markers. Instead, there are intersyllable tshegs (" "), which are superscript dots. Interword spaces play an important role in reading as word boundary information. Therefore, it is interesting to investigate the role of tshegs and what effect replacing tshegs with spaces will have on Tibetan reading. To answer these questions, Experiment 1 was conducted in which 72 Tibetan undergraduates read three-syllable-boundary conditions (normal, spaced, and untsheged). However, in Experiment 1, because we performed the experimental operations of deleting tshegs and replacing tshegs, the spatial information distribution of Tibetan sentences under different operating conditions was different, which may have a certain potential impact on the experimental results. To rule out the underlying confounding factor, in Experiment 2, 58 undergraduates read sentences for both untsheged and alternating-color conditions. Overall, the global and local analyses revealed that tshegs, spaces, and alternating-color markers as syllable boundaries can help readers segment syllables in Tibetan reading. In Tibetan reading, both spaces and tshegs are effective visual syllable segmentation cues, and spaces are more effective visual syllable segmentation cues than tshegs.

Examining the extraction of parafoveal semantic information in Tibetan.

This study conducted two experiments to investigate the extraction of semantic preview information from the parafovea in Tibetan reading. In Experiment 1, a single-factor (preview type: identical vs. semantically related vs. unrelated) within-subject experimental design was used to investigate whether there is a parafoveal semantic preview effect (SPE) in Tibetan reading. Experiment 2 used a 2 (contextual constraint: high vs. low) × 3 (preview type: identical vs. semantically related vs. unrelated) within-subject experimental design to investigate the influence of contextual constraint on the parafoveal semantic preview effect in Tibetan reading. Supporting the E-Z reader model, the experimental results showed that in Tibetan reading, readers could not obtain semantic preview information from the parafovea, and contextual constraint did not influence this process. However, comparing high- and low-constrained contexts, the latter might be more conducive to extracting semantic preview information from the parafovea.

A Preliminary Study on the Relationship between Serum Heparan Sulfate and Cancer-Related Cognitive Impairment: The Moderating Role of Oxidative Stress in Patients with Colorectal Cancer.

Cancer-related cognitive impairment (CRCI) has been frequently reported in colorectal cancer survivors. Heparan sulfate (HS) was gradually considered to be related to cognitive disorders. The effect and potential mechanism of HS on CRCI in colorectal cancer patients were unexplored. In this study, all participants were divided into a cognitive impaired group and a cognitive normal group. The concentrations of oxidative stress factors and HS in serum were detected. Associations among HS, oxidative stress factors and CRCI were evaluated. Participants with cognitive impairment exhibited increased levels of HS, GSH, SOD and MDA, compared to the patients with normal cognitive performance. The independent significant association was found between HS and CRCI after controlling for various covariates. The higher concentrations of HS were related to the decreased cognitive performance among survivors who reported higher levels of GSH (ß = 0.080, p = 0.002). Moreover, the nonlinear association between the level of HS and cognitive scores was confirmed using the restricted cubic splines (p < 0.001). These results indicated that the increased concentrations of circulating HS had a nonlinear negative connection with cognitive performance in colorectal cancer survivors, which was moderated by GSH. HS might be a new biomolecule for the identification and management of patients with CRCI.

Design, synthesis and biological evaluation of novel biphenylsulfonamide derivatives as selective AT2 receptor antagonists.

A novel series of benzenesulfonamide derivatives that selectively act on the AT2 receptor have been designed and synthesized. The binding affinity and functional activity were evaluated by radio-ligand binding analysis and cell neurite outgrowth assay, respectively. The compounds 8d, 8h, 8i, 8j, 8l, and 9h exhibited moderate selectivity and affinity for the AT2 receptor. Among them, 8j exhibited agonist activity and 8l displayed similar selectivity to the AT2 receptor with PD123,319. Molecular docking was carried out to analyze the binding mode and binding site between the compound and the AT2 receptor to provide a reference for further development.

The Mechanism of Word Satiation in Tibetan Reading: Evidence from Eye Movements.

Two eye-tracking experiments were used to investigate the mechanism of word satiation in Tibetan reading. The results revealed that, at a low repetition level, gaze duration and total fixation duration in the semantically unrelated condition were significantly longer than in the semantically related condition; at a medium repetition level, reaction time in the semantically related condition was significantly longer than in the semantically unrelated condition; at a high repetition level, the total fixation duration and reaction time in the semantically related condition were significantly longer than in the semantically unrelated condition. However, fixation duration and reaction time showed no significant difference between the similar and dissimilar orthography at any repetition level. These findings imply that there are semantic priming effects in Tibetan reading at a low repetition level, but semantic satiation effects at greater repetition levels, which occur in the late stage of lexical processing.

Quantitative age grading of mosquitoes using surface-enhanced Raman spectroscopy.

Mosquito-borne pathogens, including malaria, Zika, dengue, and chikungunya continue to be a major public health concern globally. Based on the understanding that only older female mosquitoes are infectious and represent a risk to human health, scientists have sought to age-grade mosquitoes for decades. To date, however, no reliable, cost-effective and practical methods exist to age older mosquitoes despite the tremendous epidemiological value of this approach. This study is the first attempt to develop a surface-enhanced Raman spectroscopic (SERS) method to age mosquitoes. The water extracts of Aedes aegypti mosquitoes aged 0-22 days were mixed with silver nanoparticles. The SERS spectra, which were analysed by principal component analysis and partial least square (PLS), demonstrated the capability of this approach to predict the calendar age of mosquitoes between 0 and 22 days with the coefficient of correlation (R) = 0.994 and 0.990 for PLS model calibration and validation, respectively. Spectral analysis with both SERS and infrared spectroscopy revealed the key biological sources leading to changes in spectra allowing mosquito age-grading is adenine-containing compounds and proteins. In addition, we evaluated the impact of two arthropod-borne pathogen deactivating pre-treatments (bleach and ethanol) on the discrimination capability of the SERS approach. The result shows the ethanol treatment has the potential to enhance the discrimination capability and the safety of the approach. This study represents the first step towards developing the SERS approach as a quick, reliable and field-deployable method for mosquito age-grading, which would significantly improve the effectiveness of vector-borne disease monitoring and prevention.

Eye Movement Control in Tibetan Reading: The Roles of Word Length and Frequency.

We investigated the effects of word length and frequency on eye movement control during Tibetan reading through two experiments. A preliminary experiment examined the predictive effect of word length and frequency on fixation duration and landing position using multiple linear regression analysis. In the formal experiment, we manipulated the length and frequency of target words simultaneously to investigate the effects of word length and frequency on fixation duration and landing position in Tibetan reading. In this study, we found that: (1) there were significant word-length and word-frequency effects affecting all lexical processing in Tibetan reading; (2) there are preferred viewing locations in Tibetan reading; specifically, for short words, it is the end, whereas for long words, it spans from the center to the beginning of the word; (3) word frequency does not affect preferred viewing location in Tibetan reading; (4) the preferred viewing position and the interaction of word length and viewing position found in this study supported the "strategy-tactics" approach.

Deep Learning for Rapid Identification of Microbes Using Metabolomics Profiles.

Rapid detection of viable microbes remains a challenge in fields such as microbial food safety. We here present the application of deep learning algorithms to the rapid detection of pathogenic and non-pathogenic microbes using metabolomics data. Microbes were incubated for 4 h in a protein-free defined medium, followed by 1D 1H nuclear magnetic resonance (NMR) spectroscopy measurements. NMR spectra were analyzed by spectral binning in an untargeted metabolomics approach. We trained multilayer ("deep") artificial neural networks (ANN) on the data and used the resulting models to predict spectra of unknown microbes. ANN predicted unknown microbes in this laboratory setting with an average accuracy of 99.2% when using a simple feature selection method. We also describe learning behavior of the employed ANN and the optimization strategies that worked well with these networks for our datasets. Performance was compared to other current data analysis methods, and ANN consistently scored higher than random forest models and support vector machines, highlighting the potential of deep learning in metabolomics data analysis.