Imaging bioluminescence by detecting localized haemodynamic contrast from photosensitized vasculature.

Bioluminescent probes are widely used to monitor biomedically relevant processes and cellular targets in living animals. However, the absorption and scattering of visible light by tissue drastically limit the depth and resolution of the detection of luminescence. Here we show that bioluminescent sources can be detected with magnetic resonance imaging by leveraging the light-mediated activation of vascular cells expressing a photosensitive bacterial enzyme that causes the conversion of bioluminescent emission into local changes in haemodynamic contrast. In the brains of rats with photosensitized vasculature, we used magnetic resonance imaging to volumetrically map bioluminescent xenografts and cell populations virally transduced to express luciferase. Detecting bioluminescence-induced haemodynamic signals from photosensitized vasculature will extend the applications of bioluminescent probes.

The representation of contextual cue is stimulus-specific yet its expression is flexible.

Background: Contextual cueing refers to the phenomenon in which individuals utilize frequently encountered environmental contexts, comprised of distractors, as cues to expedite a target search. Due to the conflict between the widespread occurrence of contextual cue transfer and the observed impact of changing the identity of distractors on contextual cue learning, the content of contextual cue representations remains contentious. Considering the independent nature of contextual cue learning and expression, our proposition is twofold: (1) Contextual cue representations are stimulus-specific, and (2) their expression is highly flexible. Methods: To validate the model, two experiments were conducted. Experiment 1 aimed to confirm the hypothesis that contextual cue representations are stimulus-specific. We manipulated the identity consistency of distractors within repeated scenes during contextual cue learning. Difficulty in contextual cue learning under the identity-changing condition would suggest the necessity of identity within contextual cue representation, indicating the stimulus-specific nature of these representations. Experiment 2 was designed to affirm the conclusion of Experiment 1 and explore the flexibility in the expression of contextual cue representations. This experiment comprised two phases: learning and testing. During the learning phase, participants were exposed to two sets of repeated scenes in different colors under two learning conditions: load and no-load. Working memory load was introduced to interfere with the expression to prevent it from becoming automatic. In the subsequent testing phase, the colors of the two scene sets were interchanged to impede retrieval based on identity. If both load and no-load conditions demonstrate similar levels of contextual cue effects during the testing phase, it implies the flexibility in the expression of contextual cue representations and confirms the conclusion of Experiment 1. Results: In Experiment 1, a notable contextual cue learning effect was observed under the identity-consistent condition (p = 0.001). However, this effect was not evident under the identity-changing condition (p = 0.286). This finding strongly supports the stimulus-specific nature of contextual cue representation. In Experiment 2, the contextual cueing effect appeared but did not show a significant difference between the two conditions (t(23) = 0.02, p = 0.987, BF10 = 0.215), indicating the cognitive system's ability to flexibly redefine retrieval cues. This adaptability aligns with our hypothesis and confirms the high flexibility in the expression process of contextual cue representations and confirms the conclusion of Experiment 1.

Presence of Epstein-Barr virus in cerebrospinal fluid is associated with increased mortality in HIV-negative cryptococcal meningitis.

Cryptococcus neoformans is the most common cause of fungal meningitis and is associated with a high mortality. The clinical significance of concurrent Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-negative patients with cryptococcal meningitis (CM) remains unclear. A retrospective cohort study was performed by analyzing CSF samples from 79 HIV-negative Chinese Han patients with confirmed CM. We identified CSF viral DNA in these patients by metagenomic next-generation sequencing (mNGS) and compared 10-week survival rates among those with and without EBV DNA in CSF. Of 79 CSF samples tested, 44.3% (35/79) had detectable viral DNA in CSF, while 55.7% (44/79) were virus-negative. The most frequent viral pathogen was EBV, which was detected in 22.8% (18/79) patients. The median number of CSF-EBV DNA reads was 4 reads with a range from 1 to 149 reads. The 10-week mortality were 22.2% (4/18) in those with positive-CSF-EBV and 2.3% (1/44) in those with negative-CSF-virus (hazard ratio 8.20, 95% confidence interval [CI] 1.52-81.80; p=0.014), which remained significant after a multivariate adjustment for the known risk factors of mortality (adjusted hazard ratio 8.15, 95% CI 1.14-92.87; p=0.037). mNGS can identify viruses that coexist in CSF of HIV-negative patients with CM. EBV DNA is most commonly found together with Cryptococcus neoformans in CSF and its presence is associated with increased mortality in HIV-negative CM patients.

Children's food allergy: Effects of environmental influences and antibiotic use across critical developmental windows.

BACKGROUND: Increasing studies linked outdoor air pollution (OAP), indoor environmental factors (IEFs), and antibiotics use (AU) with the first wave of allergies (i.e., asthma, allergic rhinitis, and eczema), yet the role of their exposures on children's second wave of allergy (i.e., food allergy) are unknown. OBJECTIVES: To investigate the association between exposure to OAP and IEFs and childhood doctor-diagnosed food allergy (DFA) during the pre-pregnancy, prenatal, early postnatal, and current periods, and to further explore the effect of OAP and IEFs on DFA in children co-exposed to antibiotics. METHODS: A retrospective cohort study involving 8689 preschoolers was carried out in Changsha, China. Data on the health outcomes, antibiotic use, and home environment of each child were collected through a questionnaire. Temperature and air pollutants data were obtained from 8 and 10 monitoring stations in Changsha, respectively. Exposure levels to temperature and air pollutants at individual home addresses were calculated by the inverse distance weighted (IDW) method. Multiple logistic regression models were employed to assess the associations of childhood DFA with exposure to OAP, IEF, and AU. RESULTS: Childhood ever doctor-diagnosed food allergy (DFA) was linked to postnatal PM10 exposure with OR (95% CI) of 1.18 (1.03-1.36), especially for CO and O3 exposure during the first year with ORs (95% CI) = 1.08 (1.00-1.16) and 1.07 (1.00-1.14), as well as SO2 exposure during the previous year with OR (95% CI) of 1.13 (1.02-1.25). The role of postnatal air pollution is more important for the risk of egg, milk and other food allergies. Renovation-related IAP (new furniture) and dampness-related indoor allergens exposures throughout all time windows significantly increased the risk of childhood DFA, with ORs ranging from 1.23 (1.03-1.46) to 1.54 (1.29-1.83). Furthermore, smoke-related IAP (environmental tobacco smoke [ETS], parental and grandparental smoking) exposure during pregnancy, first year, and previous year was related to DFA. Additionally, exposure to pet-related indoor allergens (cats) during first year and total plant-related allergens (particularly nonflowering plants) during previous year were associated with DFA. Moreover, exposure to plant-related allergy during first and previous year was specifically associated with milk allergy, while keeping cats during first year increased the risk of fruits/vegetables allergy. Life-time and early-life AU was associated with the increased risk of childhood DFA with ORs (95% CI) = 1.57 (1.32-1.87) and 1.46 (1.27-1.67), including different types food allergies except fruit/vegetable allergy. CONCLUSIONS: Postnatal OAP, life-time and early-life IEFs and AU exposure played a vital role in the development of DFA, supporting the "fetal origin of childhood FA" hypothesis.

Smoking may increase the usage of antidepressant: evidence from genomic perspective analysis.

This study uses the two-sample Mendelian randomization (TSMR) method to explore the causal relationships between smoking initiation (SMKI), never smoking (NSMK), past tobacco smoking (PTSMK), and the usage of antidepressants (ATD). Single-nucleotide polymorphisms (SNPs) with genome-wide significance (P < 5E-08) related to SMKI, NSMK, and PTSMK were selected from the genome-wide association study (GWAS) database as instrumental variables (IVs). The main method, inverse variance weighted (IVW), was utilized to investigate the causal relationship. The results demonstrated a positive causal relationship between SMKI and ATD use, where SMKI leads to an increase in ATD use. Conversely, NSMK and PTSMK showed a negative causal relationship with ATD use, meaning that NSMK and PTSMK lead to a reduction in ATD use. Additionally, sensitivity analysis showed that the results of this study were robust and reliable. Using the TSMR method and from a genetic perspective, this study found that SMKI leads to an increase in ATD use, while NSMK and PTSMK reduce ATD use.

Genomic and phenotypic characterization of Thermosynechococcus-like strains reveals eight species within the genus Thermosynechococcus and a novel genus Parathermosynechococcus gen. nov.

Thermophilic unicellular cyanobacteria of the family Thermosynechococcaceae are essential primary producers and integral components of many microbial mats found in hot springs of Asia and North America. Historically, based on their simple morphology, these organisms, along with members of taxonomically unrelated thermophilic Thermostichaceae have been described with a generic term, "Synechococcus", used for elongated unicellular cyanobacteria. This has created significant misperception in the scientific literature regarding the taxonomic status of these essential thermophilic primary producers and their relationship with Synechococcus sensu stricto. In this manuscript, we attempted a genome-driven taxonomic reevaluation of the family Thermosynechococcaceae. Application of genomic analyses such as GTDB classification, ANI/AAI and phylogenomics support the delineation of eight species within genus Thermosynechococcus. Two subspecies were further identified within T. taiwanensis by dDDH and phylogenomics. Moreover, the results also suggest the presence of two putative new genera phylogenetically alongside genus Thermosynechococcus, a thermophilic genus Parathermosynechococcus represented by PCC 6715 and a non-thermophilic genus represented by PCC 6312. The proposed genospecies and new genera were further integrated with morphological and/or ecological information. Interestingly, the phylogeny of 16S-23S ITS achieved a better taxonomic relationship than that of 16S rRNA and supported the genome-based classification of Thermosynechococcus spp. Finally, the pan-genome analysis indicated a conserved pattern of genomic core among known members of Thermosynechococcus.

The modern face of esophageal candidiasis in an oncology center: Correlating clinical manifestations, endoscopic grade, and pathological data in 323 contemporary cancer patients.

OBJECTIVES: Clinical presentation and outcomes of esophageal candidiasis (EC) in cancer patients are scarcely studied in the azole era, as is the correlation between clinical, endoscopic, and histopathological EC manifestations. METHODS: We retrospectively reviewed the risk factors, clinical features, and outcomes of pathology-documented EC cases at MD Anderson Cancer Center. We further assessed associations between presence of symptoms, standardized 4-stage endoscopic grade (Kodsi classification), histopathological data, and fluconazole treatment failure. RESULTS: Among 323 cancer patients with EC, 89% had solid tumors, most commonly esophageal cancer (29%). Thirty-three percent of EC patients were asymptomatic. The proportion of symptomatic EC patients significantly increased with endoscopic grade (P = 0.005). Among 202 patients receiving oral fluconazole, 27 (13%) had treatment failure. Underlying esophageal disease was the only independent predictor of fluconazole treatment failure (odds ratio: 3.88, P = 0.005). Endoscopic grade correlated significantly with Candida organism burden (Correlation coefficient [ρ] = 0.21, P < 0.01) and neutrophilic inflammation (ρ = 0.18, P < 0.01). Candida invasion of the squamous mucosal layer was associated with treatment failure (P = 0.049). CONCLUSIONS: EC was predominantly encountered in patients with solid tumors. One-third of EC patients were asymptomatic, challenging traditional symptom-based diagnosis. The development of integrated clinicopathological scoring systems could further guide the therapeutic management of cancer patients with EC.

Nanoconfinement of Carbon Dioxide within Interfacial Aqueous/Ionic Liquid Systems.

Nanoporous, gas-selective membranes have shown encouraging results for the removal of CO2 from flue gas, yet the optimal design for such membranes is often unknown. Therefore, we used molecular dynamics simulations to elucidate the behavior of CO2 within aqueous and ionic liquid (IL) systems ([EMIM][TFSI] and [OMIM][TFSI]), both confined individually and as an interfacial aqueous/IL system. We found that within aqueous systems the mobility of CO2 is reduced due to interactions between the CO2 oxygens and hydroxyl groups on the pore surface. Within the IL systems, we found that confinement has a greater effect on the [EMIM][TFSI] system as opposed to the [OMIM][TFSI] system. Paradoxically, the larger and more asymmetrical [OMIM]+ molecule undergoes less efficient packing, resulting in fewer confinement effects. Free energy surfaces of the nanoconfined aqueous/IL interface demonstrate that CO2 will transfer spontaneously from the aqueous to the IL phase.

Exploring adverse events of Vilazodone: evidence from the FAERS database.

OBJECTIVE: This study aims to conduct an exhaustive evaluation of Vilazodone's safety in clinical application and to unearth the potential adverse event (AE) risks associated with its utilization based on FDA Adverse Event Reporting System (FAERS) database. METHODS: This research employed data spanning from the first quarter of 2011 to the third quarter of 2023 from the FAERS database. Various signal detection methodologies, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were utilized to ascertain the correlation between Vilazodone and specific AEs. RESULTS: The study compiled a total of 17,439,268 reports of drug AEs, out of which 5,375 were related to Vilazodone. Through signal mining, 125 Preferred Terms (PTs) encompassing 27 System Organ Classes (SOCs) were identified. The findings indicated a higher prevalence among females and patients within the 45 to 65 age bracket. The principal categories of AEs included Psychiatric disorders, Nervous system disorders, and Gastrointestinal disorders, with prevalent incidents of Diarrhoea, Nausea, and Insomnia. Moreover, the study identified robust signals of novel potential AEs, notably in areas such as sleep disturbances (Sleep paralysis, Hypnagogic hallucination, Rapid eye movements sleep abnormal, Sleep terror, Terminal insomnia, Tachyphrenia), sexual dysfunctions (Female orgasmic disorder, Orgasm abnormal, Disturbance in sexual arousal, Spontaneous penile erection, Anorgasmia, Sexual dysfunction, Ejaculation delayed), and other symptoms and injuries (Electric shock sensation, Violence-related symptom, Gun shot wound). CONCLUSION: Although Vilazodone presents a positive prospect in the management of MDD, the discovery of AEs linked to its use, particularly the newly identified potential risks such as sleep and sexual dysfunctions, necessitates heightened vigilance among clinicians.

Oculomotor Nerve Palsy Induced by a Cerebral Developmental Venous Anomaly: A Case Report and Comprehensive Review.

BACKGROUND Symptoms caused by developmental venous anomalies (DVAs) are usually mild and unspecific. Despite the benign nature of DVAs, they can occasionally be symptomatic. CASE REPORT A 67-year-old woman presented with sudden diplopia and left eyelid ptosis for 10 days. A neurologic examination revealed left complete oculomotor nerve palsy. Other neurologic deficits, including eye pain or pulsatile tinnitus, were not detected. Furthermore, the visual acuity was normal. Additionally, no retinal hemorrhage, venous dilatation, or fundus tortuosity were observed. No ischemia lesions or neoplasms were observed in MRI, and no widening or enhancement of the cavernous sinus was detected in post-contrast T1-weighted images, but magnetic resonance tomography cerebral angiography (MRTA) detected an offending vessel compressing the left oculomotor nerve in the fossa interpeduncular. We hypothesized that oculomotor nerve palsy (ONP) was caused by an abnormal arterial structure. However, digital subtraction angiography (DSA) revealed no aneurysm or abnormal arterial structure in the arterial phase, while a tortuous and dilated collecting vein was detected in the venous phase, connecting the left temporal lobe to the left cavernous sinus. This indicated a typical caput medusae appearance, suggesting the mechanism of oculomotor palsy caused by compressive impairment of the DVA. The patient refused microvascular decompression surgery, and ONP persisted after 30 days. Management was conservative, with spontaneous resolution at 60 days and no recurrence during the 2-year follow-up. CONCLUSIONS ONP is rarely caused by DVAs, which are easily ignored due to their benign nature. Cerebral vein examinations are advised for patients exhibiting clinical symptoms of unknown etiology.

Evaluating spray drift from Uncrewed Aerial Spray Systems: A machine learning and variance-based sensitivity analysis of environmental and spray system parameters.

Uncrewed Aerial Spray Systems (UASS), commonly called drones, have become an important application technique for plant protection products in Asia and worldwide. As such, environmental variables and spray system parameters influencing spray drift deserve detailed investigations. This study presents the data analysis of 114 UASS drift trials conducted between December 2021 and December 2022 in China. Study design was based on the ISO 22866:2005 protocol for spray drift trials and considered different UASS platforms, nozzles, and release heights, and specifically continuously measured weather conditions. The relative importance of the environmental variables and spray system parameters was evaluated by a random forest (RF) feature importance analysis, a Sobol sensitivity analysis and partial dependence plots. This approach was preferred to linear ranking techniques such as ANOVA (analysis of variance) due to the non-linearity of the system. In addition, partial dependence plots are proposed to visualize the relationship between specific input parameters within the system. Drift deposition curves calculated from the 114 trials show good agreement with previous UASS trials reported in the literature. As reported in previous studies, spray drift following UASS applications is lower than for manned aerial vehicles, greater than for ground spray applications, and similar to drift observed from orchard air blast applications. In addition, 9 trials were conducted on corn fields in order to evaluate the potential effect of crop cover on spray drift. Spray drift was observed to be reduced over the cropped soil, suggesting that plant cover might possibly reduce spray drift. These findings could help supporting drift mitigation policies, stewardship advice and product labelling around the world.

Improving Buried Interface Contact by Bidentate Anchoring for Inverted Perovskite Solar Cells.

Nickel oxide (NiOx) is a promising hole transport layer (HTL) to fabricate efficient and large-scale inverted perovskite solar cells (PSCs) due to its low cost and superior chemical stability. However, inverted PSCs based on NiOx are still lagging behind that of other HTL because of the poor quality of buried interface contact. Herein, a bidentate ligand, 4,6-bis (diphenylphosphino) phenoxazine (2DPP), is used to regulate the NiOx surface and perovskite buried interface. The diphosphine Lewis base in the 2DPP molecule can coordinate both with NiOx and lead ions at NiOx/perovskite interface, leading to high-quality perovskite films with minimized defects. It is found that the inverted PSCs with 2DPP-modified buried interface exhibit double advantages of being both fast charge extraction and reduced nonradiative recombination, which is a combination of multiple factors including favorable energetic alignment, improved interface contact and strong binding between NiOx/2DPP and perovskite. The optimal PSC based on 2DPP modification yields a champion power conversion efficiency (PCE) of 21.9%. The unencapsulated PSC maintains above 75% of its initial PCE in the air with a relative humidity (RH) of 30-40% for 1000 h.

Analysis of antimicrobial drug usage in psychiatric specialized hospitals during the pandemic in China.

BACKGROUND: This study aims to compare antimicrobial drug usage in our hospital to Jiangsu Province and China from 2020 to 2022. RESEARCH DESIGN AND METHODS: A detailed analysis was performed using data from the National Antimicrobial Drug Clinical Application Monitoring Network. Several parameters were studied: the rate of antimicrobial drug use, number and types of drugs used, the rate of combined use, rate of microbiological examinations, drug use intensity, and cumulative Defined Daily Doses (DDDs). RESULTS: From 2020 to 2022, our hospital's antimicrobial drug usage rate was consistently lower than Jiangsu Province and China. The average number of drug types and the combined drug use rate were higher in 2020 but fell below those in Jiangsu Province and China in 2021 and 2022. Our microbiological examination rate consistently surpassed that of Jiangsu Province and China. Furthermore, our Antimicrobial Usage Density and cumulative DDDs were notably lower. While AUD remained stable, DDDs showed a decreasing trend. The most dominant drug in DDDs was cefditoren, a third-generation cephalosporin. CONCLUSIONS: During the pandemic years, our hospital not only met the requirements for antimicrobial drug usage, microbiological examination, AUD, and cumulative DDDs but also demonstrated a consistent year-by-year decrease in drug usage and DDDs.

Case report: Preventive infusion of donor-derived CD7 chimeric antigen receptor T cells after allogeneic hematopoietic stem cell transplantation.

Chimeric antigen receptor T cells (CAR T) targeting CD7 for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) showed promising efficacy and safety in some clinical trials. However, most of them were bridged with allogeneic hematopoietic stem cell transplantation (allo-HSCT). We described successful treatment with preventive donor-derived anti-CD7 CAR-T therapy in a case of refractory T lymphoblastic lymphoma following allo-HSCT, who could not receive autologous anti-CD7 CAR-T products due to the low-quality of T lymphocytes. To date, the patient's complete remission has persisted for 20 months after HSCT.

A Reaction-based Ratiometric Fluorescent Probe with Large STOKES Shift for Cu2+ in Neat Aqueous Solution.

A novel reaction-based ratiometric fluorescent probe 1 for Cu2+ using picolinate as the reaction site and hemicyanine as the fluorophore was developed. 1 displayed maximum absorption peak at 355 nm and fluorescence emission peak at 500 nm, with large Stokes shift of 145 nm. Upon reaction with Cu2+, the maximum absorption and fluorescence emission peaks red-shifted to 390 nm and 570 nm respectively, owing to Cu2+-induced hydrolysis of the picolinate moiety in 1. Meanwhile, the solution of 1 turned from green to orange under a 365 nm UV lamp. 1 not only could detect Cu2+ ratiometrically by the ratios of both absorbance (A390 nm/A355 nm) and fluorescence intensity (F570 nm/F500 nm), but also displayed large Stokes shift, fast response, high sensitivity and excellent selectivity over other metal ions in neat aqueous solution.

Mitigating the Overheat of Stretchable Electronic Devices Via High-Enthalpy Thermal Dissipation of Hydrogel Encapsulation.

The practical application of flexible and stretchable electronics is significantly influenced by their thermal and chemical stability. Elastomer substrates and encapsulation, due to their soft polymer chains and high surface-area-to-volume ratio, are particularly susceptible to high temperatures and flame. Excessive heat poses a severe threat of damage and decomposition to these elastomers. By leveraging water as a high enthalpy dissipating agent, here, a hydrogel encapsulation strategy is proposed to enhance the flame retardancy and thermal stability of stretchable electronics. The hydrogel-based encapsulation provides thermal protection against flames for more than 10 s through the evaporation of water. Further, the stretchability and functions automatically recover by absorbing air moisture. The incorporation of hydrogel encapsulation enables stretchable electronics to maintain their functions and perform complex tasks, such as fire saving in soft robotics and integrated electronics sensing. With high enthalpy heat dissipation, encapsulated soft electronic devices are effectively shielded and retain their full functionality. This strategy offers a universal method for flame retardant encapsulation of stretchable electronic devices.

Investigation of autophagy­related genes and immune infiltration in calcific aortic valve disease: A bioinformatics analysis and experimental validation.

The present study aimed to elucidate the role of autophagy-related genes (ARGs) in calcific aortic valve disease (CAVD) and their potential interactions with immune infiltration via experimental verification and bioinformatics analysis. A total of three microarray datasets (GSE12644, GSE51472 and GSE77287) were obtained from the Gene Expression Omnibus database, and gene set enrichment analysis was performed to identify the relationship between autophagy and CAVD. After differentially expressed genes and differentially expressed ARGs (DEARGs) were identified using CAVD samples and normal aortic valve samples, a functional analysis was performed, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, protein-protein interaction network construction, hub gene identification and validation, immune infiltration and drug prediction. The results of the present study indicated a significant relationship between autophagy and CAVD. A total of 46 DEARGs were identified. GO and pathway enrichment analyses revealed the complex roles of DEARGs in regulating CAVD, including multiple gene functions and pathways. A total of 10 hub genes were identified, with three (SPP1, CXCL12 and CXCR4) consistently upregulated in CAVD samples compared with normal aortic valve samples in multiple datasets and experimental validation. Immune infiltration analyses demonstrated significant differences in immune cell proportions between CAVD samples and normal aortic valve samples, thus showing the crucial role of immune infiltration in CAVD development. Furthermore, therapeutic drugs were predicted that could target the identified hub genes, including bisphenol A, resveratrol, progesterone and estradiol. In summary, the present study illuminated the crucial role of autophagy in CAVD development and identified key ARGs as potential therapeutic targets. In addition, the observed immune cell infiltration and predicted autophagy-related drugs suggest promising avenues for future research and novel CAVD treatments.

Incident Functional Limitations Among Older Adults With Diabetes During the COVID-19 Pandemic: An Analysis of Prospective Data From the Canadian Longitudinal Study on Aging.

OBJECTIVES: The objectives of this study were: 1) to examine and compare changes in functional limitations during the COVID-19 pandemic among older adults with and without diabetes; and 2): to identify key risk factors associated with developing functional limitations among older adults with and without diabetes during the pandemic. METHODS: We analyzed data collected from the Canadian Longitudinal Study on Aging. The analysis was restricted to those with no functional limitations in the follow-up 1 wave (2015 to 2018) (final sample N=6,045). Regression models were used to describe associations between diabetic status and functional limitation outcomes. We conducted stratified analyses to evaluate whether these associations varied by sociodemographic indicators. We also predicted the probability of the development of ≥1 functional limitation among those with and without diabetes for various patient profiles. RESULTS: Older adults with diabetes were 1.28-fold (95% confidence interval 1.02 to 1.60) more likely to develop ≥1 functional limitation than older adults without diabetes after controlling for relevant sociodemographic and health covariates. Risk factors for incident functional limitations among older adults, both with and without diabetes, include increasing age, low socioeconomic status, obesity, multimorbidity, and physical inactivity. CONCLUSIONS: Our findings indicate that older adults with diabetes were at an increased risk of developing functional limitations during the pandemic when compared with older adults without diabetes, even when controlling for several key risk factors. Targetting modifiable risk factors, such as physical activity, may help to reduce the risk of functional limitations among older adults with diabetes.

Mining and analysis of security alert signals of valbenazine based on the Food and Drug Administration Adverse Event Reporting System database.

BACKGROUND: Valbenazine is used for tardive movement disorders in adults. Current studies on its safety are mostly from clinical trials and small case reports, limiting information on rare adverse reactions. This study investigated valbenazine-related adverse event (AE) risk signals using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Valbenazine AEs data were collected from the FAERS database from 2017 Q2 to 2023 Q1, employing methods like reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and empirical Bayesian geometric mean. RESULTS: After data cleaning and drug screening, there were 20,837 AEs primarily suspecting valbenazine, involving 26 system organ classes and 125 AEs related to valbenazine at the preferred terms level. AEs related to valbenazine were mainly concentrated in nervous system disorders, general disorders and administration site conditions, and psychiatric disorders. Eye disorders and gastrointestinal disorders are new AEs not labeled in the valbenazine instructions. In addition, some new potential AE signals were found, such as Tardive dyskinesia and eyelid function disorder. CONCLUSION: The common AEs of valbenazine in the real world are consistent with the instructions, but there are some newly discovered suspicious AEs.

Exploring ncRNA-Drug Sensitivity Associations Via Graph Contrastive Learning.

Increasing evidence has shown that noncoding RNAs (ncRNAs) can affect drug efficiency by modulating drug sensitivity genes. Exploring the association between ncRNAs and drug sensitivity is essential for drug discovery and disease prevention. However, traditional biological experiments for identifying ncRNA-drug sensitivity associations are time-consuming and laborious. In this study, we develop a novel graph contrastive learning approach named NDSGCL to predict ncRNA-drug sensitivity. NDSGCL uses graph convolutional networks to learn feature representations of ncRNAs and drugs in ncRNA-drug bipartite graphs. It integrates local structural neighbours and global semantic neighbours to learn a more comprehensive representation by contrastive learning. Specifically, the local structural neighbours aim to capture the higher-order relationship in the ncRNA-drug graph, while the global semantic neighbours are defined based on semantic clusters of the graph that can alleviate the impact of data sparsity. The experimental results show that NDSGCL outperforms basic graph convolutional network methods, existing contrastive learning methods, and state-of-the-art prediction methods. Visualization experiments show that the contrastive objectives of local structural neighbours and global semantic neighbours play a significant role in contrastive learning. Case studies on two drugs show that NDSGCL is an effective tool for predicting ncRNA-drug sensitivity associations. Source code and datasets can be available on https://github.com/altriavin/NDSGCL.