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siRNA-mediated inhibition of hTERT enhances the effects of curcumin in promoting cell death in precursor-B acute lymphoblastic leukemia cells: an in silico and in vitro study

Measurement properties of instruments to assess insight in psychosis: A systematic review protocol

Introduction Insight in psychosis, defined as a patient’s awareness and judgment of their mental illness, is a complex and evolving concept. Historically, the absence of insight was considered a defining characteristic of psychosis, but recent decades have seen the development of structured tools for its assessment. This systematic review aims to critically appraise the measurement properties of instruments used to assess insight in individuals with schizophrenia spectrum, bridging the gap between theoretical conceptualization and clinical practice. Methods This protocol is reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. Eligible studies will evaluate instruments measuring insight in psychosis, including self-report, observer ratings, behavioral measurements, and semi-structured interviews. The psychometric properties assessed will encompass reliability, validity, responsiveness, interpretability, and clinical utility. We will include primary quantitative studies published in peer-reviewed journals and available in English. Results Two reviewers will conduct data extraction and quality assessment independently, with discrepancies resolved through consensus or a third reviewer. The COSMIN Risk of Bias checklist and the GRADE approach will be used to evaluate each measure’s methodological quality and overall strength of evidence. Discussion This systematic review will synthesize current evidence on insight measurement in psychosis, providing a comprehensive overview of the strengths and limitations of existing instruments. The findings will inform future research and clinical practice, facilitating the selection of the most appropriate tools for assessing insight and ultimately contributing to improved care for individuals with psychosis. The findings will provide clinicians and researchers with robust tools for assessing insight, ultimately enhancing treatment outcomes for individuals with psychosis.

Development of a checklist for cognitive assessment requirements (CARE) based on a Delphi consensus study

Low agreement and frequent invalid controls in two SARS-CoV-2 T-cell assays in people with compromised immune function

T-cell response plays an important role in SARS-CoV-2 immunogenicity. For people living with HIV (PWH) and solid organ transplant (SOT) recipients there is limited evidence on the reliability of commercially available T-cell tests. We assessed 173 blood samples from 81 participants (62 samples from 35 PWH; 111 samples from 46 SOT recipients [lung and kidney]) with two commercial SARS-CoV-2 Interferon-γ (IFN-γ) release assays (IGRA; SARS-CoV-2 IGRA by Euroimmun, and IGRA SARS-CoV-2 by Roche). The reliability between the tests was judged as low (Cohen’s kappa [κ] = 0.20; overall percent agreement [OPA] = 66%). A high proportion of tests were invalid (22% Euroimmun; 8% Roche). When excluding these invalid tests, the agreement was higher (κ  =  0.43; OPA = 90%). The low reliability between the two T-cell tests indicates that results should be interpreted with caution in SOT recipients and PWH and that SARS-CoV-2 T-cell tests need to be optimized and further validated for use in vulnerable patient populations.

The association between the dietary inflammatory index and multiple myeloma: a case–control study

Identification of hypertension gene expression biomarkers based on the DeepGCFS algorithm

Hypertension is a critical risk factor and cause of mortality in cardiovascular diseases, and it remains a global public health issue. Therefore, understanding its mechanisms is essential for treating and preventing hypertension. Gene expression data is an important source for obtaining hypertension biomarkers. However, this data has a small sample size and high feature dimensionality, posing challenges to biomarker identification. We propose a novel deep graph clustering feature selection (DeepGCFS) algorithm to identify hypertension gene biomarkers with more biological significance. This algorithm utilizes a graph network to represent the interaction information between genes, builds a GNN model, designs a loss function based on link prediction and self-supervised learning ideas for training, and allows each gene node to obtain a feature vector representing global information. The algorithm then uses hybrid clustering methods for gene module detection. Finally, it combines integrated feature selection methods to determine the gene biomarkers. The experiment revealed that all the ten identified hypertension biomarkers were significantly differentiated, and it was found that the classification performance of AUC can reach 97.50%, which is better than other literature methods. Six genes (PTGS2, TBXA2R, ZNF101, KCNJ2, MSRA, and CMTM5) have been reported to be associated with hypertension. By using GSE113439 as the validation dataset, the AUC value of classification performance was to be 95.45%, and seven of the genes (LYSMD3, TBXA2R, KLC3, GPR171, PTGS2, MSRA, and CMTM5) were to be significantly different. In addition, this algorithm’s performance of gene feature vector clustering was better than other comparative methods. Therefore, the proposed algorithm has significant advantages in selecting potential hypertension biomarkers.

Disrupted HIV care during COVID-19 pandemic associated with increased disabilities among people living with HIV in Belize

The impact of a commercial lower extremity exoskeleton on metabolic load, perceived exertion, and physiological response to a challenging military relevant task: A randomized cross-over design pilot study

Purpose To assess physiological metrics during the use of a commercially available bilateral active ankle exoskeleton during a challenging military-relevant task and if use of the exoskeleton during this task influences: metabolic load, physiological measures or rate of perceived exertion. Methods Nine healthy volunteers (5M, 4F) completed this randomized cross-over design trial, with a baseline visit and two randomized test sessions (with/without the exoskeleton). Variables included impact on time to exhaustion during walking on a treadmill at varying speeds and gradients (0–15%) at 26.7°C, 50% humidity with a loaded rucksack (30% body weight). The primary outcome measure was change in metabolic cost with/without the exoskeleton (O2 consumption, metabolic equivalents); secondary outcomes were change in heart rate and perceived exertion between conditions. Results Participants averaged 22.4 ± 4.5 years old, 173.7 ± 7.4 cm tall, weighed 80.9 ± 13.9 kg, and VO2max of 43.8 ± 10.6 mL/kg/min. Total kcals did not differ between conditions (with/without exoskeleton; t = 0.98; p = 0.357). Kcals/min were significantly lower (1.06 kcals/min) with the exoskeleton (t = 3.94; p = 0.004). Average oxygen consumption (VO2) was significantly lower (2.36 mL/kg/min) with the exoskeleton (t = 2.81; p = 0.023), and peak VO2 was 3.33 mL/kg/min lower with the exoskeleton (t = 2.37; p = 0.045). Peak and Average METS were also lower with the exoskeleton by 0.98 (t = 2.61; p = 0.031) and 1.23 (t = 2.39; p = 0.044) respectively. Conclusions Results suggest a powered ankle exoskeleton may decrease energy consumption during military relevant tasks when conducted in a laboratory environment. There may also be physiological benefits such as reduced core temperate and heart rate. Replication of this work in the field environment is warranted.

Modeling of historical and future changes in temperature and precipitation in the Panj River Basin in Central Asia under the CMIP5 RCP and CMIP6 SSP scenarios

Influences of roughness and filling degree on the shear strength and damage evolution characteristics of cement-filled joints

The shear resistance of filling joints is an important factor affecting the stability of rock joints. Pressure-shear tests of cement-filled joints were carried out. Combined with the acoustic emission (AE) technique, the effects of normal stress, roughness and filling degree on the shear strength, damage morphology and damage evolution of cement-filled joints were investigated. The results show that with the increase of roughness, the failure mode is more complicated. When the roughness is low, only the bonding surface of the interface between the filler and the joint surface is damaged, and the filling degree has a weak effect on the failure mode. When the roughness is high, with the increase of normal stress and filling degree, the failure of the filled joint is from the joint failure of the bonding surface and the filling material to the serious failure of the bonding surface, the filling material and the joint. The peak shear strength of filled joints is positively correlated with roughness and negatively correlated with filling degree. With the increase of filling degree, the influence of roughness will be weakened by filling material, and the normal stress will amplify the effect of roughness. The evolution characteristics of AE show that the damage degree of filled joints is positively correlated with normal stress and roughness, and negatively correlated with filling degree. The joint surface is damaged locally at first, then failure near the main raised body of the joint, and finally spreads to the whole joint surface.

miR-224 activates cancer-associated fibroblasts to enhance lung cancer cell migration and invasion by targeting Akirin1

Usual prevention in unusual settings: A scoping review of place-based health interventions in public-facing businesses

Place-based health interventions may help reach underserved populations. This scoping review summarizes the peer-reviewed literature on the type and effects of place-based health interventions in unconventional public-facing business settings (e.g., retail and services). A literature search was conducted in PubMed, Google Scholar, and APA PsycNet for studies from 1990–2023. Inclusion criteria for studies were: conducted in the United States, delivered a health intervention, based on an unconventional business setting, and targeted a specific health condition. An initial search yielded 2,727 unduplicated studies, which was filtered to 42 studies included in this review. These 42 studies were categorized based on health conditions of focus, including cardiovascular health (12 studies); HIV (6 studies); diabetes (5 studies); cancers (13 studies); and all other conditions (14 studies). The most common unconventional public-facing business settings for health interventions included barbershops or beauty salons; interventions included health education, preventative screenings, pharmacy services, and connections to local healthcare providers and resources. Notably, 34 (81%) of the studies targeted Black populations. Studies reported positive responses from participants for place-based interventions, increased awareness and screening of health conditions, more referrals to healthcare services, and improved health outcomes. While there have been 9 randomized trials conducted across various health conditions, these trials are limited to focus on a few select settings and lack of objective health outcome measures. These findings highlight the need for more rigorously designed studies in diverse settings that can effectively evaluate the impact of place-based health interventions. The existing literature suggests health interventions delivered in public-facing business settings may be a promising strategy to reach underserved populations.

Immune infiltrate populations within distinct tumor immune microenvironments predictive of immune checkpoint treatment outcome

Relationship between floating toe score and performance in track and field athletes

This study explored the relationship between floating toes and athletic performance among collegiate track and field athletes. A total of 422 athletes (sprinters, jumpers, and distance runners) and 136 controls participated in this study. Plantar surface images were captured using a specially designed foot scanner during standing to calculate the floating toe score. The score, which sums the floating toe points of all toes, categorizes them into ‘floating toe’, ‘incomplete contact’, or ‘normal toe’. The World Athletics score served as a measure of athletic performance. Overall, collegiate track and field athletes had a significantly higher mean floating toe score (14.22 ± 4.87 points) than controls (11.06 ± 6.05 points) (p < 0.05), suggesting that fewer floating toes may confer a performance advantage. Within the track and field events, sprinters and jumpers showed significantly higher floating toe scores than distance runners (p < 0.05), emphasizing the variations in floating toes across different events. Although no significant correlation between floating toe score and World Athletics score was observed overall, a significantly negative correlation was found among distance runners (r = -0.25, p = 0.006), indicating that distance runners with higher athletic performance tend to have more pronounced floating toes. These findings suggest a nuanced relationship between floating toes and various aspects of track and field performance, particularly in distance running.

The daily relations of co-rumination and perseverative cognition

Abstract Emotion regulation plays a crucial role in responding to daily stressors. While intrapersonal emotion regulation has received significant attention, the role of interpersonal emotion regulation remains understudied. This study aimed to explore the associations between intrapersonal perseverative cognition (i.e., rumination and worry) and interpersonal perseverative cognition (i.e., co-rumination), in the context of daily negative events. A daily diary study was conducted with a sample of university students (N = 178). The study comprised a baseline survey assessing trait-level variables, followed by a diary study where participants were sent an approximately two-minute-long survey every evening for 10 consecutive days. The findings indicated that daily co-rumination was associated with daily intrapersonal perseverative cognition, even when controlling for trait-level worry. The association between intra- and interpersonal perseverative cognition was stronger in the presence of daily negative events. Our findings indicate a need for further investigation into the contemporaneous relationship between co-rumination and intrapersonal rumination/worry, to ascertain their unique or joint adverse effects on mental health, especially within the context of daily negative events.

Structure-guided identification of mitogen-activated protein kinase-1 inhibitors towards anticancer therapeutics

Mitogen-activated protein kinase 1 (MAPK1) is a serine/threonine kinase that plays a crucial role in the MAP kinase signaling transduction pathway. This pathway plays a crucial role in various cellular processes, including cell proliferation, differentiation, adhesion, migration, and survival. Besides, many chemotherapeutic drugs targeting the MAPK pathway are used in clinical practice, and novel inhibitors of MAPK1 with improved specificity and efficacy are required. Hence, targeting MAPK1 can be crucial to control metastasis in cancer therapeutics. In this study, we utilized a structure-guided virtual screening approach to screen a library of thousands of natural compounds from the ZINC database. The Lipinski rule of five (RO5) was used as a criterion for the primary selection of natural compounds. The screened compounds were prioritized based on their binding affinity, docking scores, and specificity towards the kinase domain of MAPK1 during the molecular docking process. Subsequently, the selected hits underwent rigorous screening that included the identification of potential pan-assay interference compounds (PAINS), ADMET evaluation, and prediction of pharmacological activities using PASS analysis. Afterwards, we performed a comprehensive interaction analysis to explore the binding prototypes of the screened molecules with the key residues within the MAPK1 kinase domain. Finally, selected molecules underwent extensive all-atom molecular dynamics (MD) simulations for a time duration of 200 nanoseconds. The study pinpointed three natural compounds with ZINC database IDs ZINC0209285, ZINC02130647, and ZINC02133691 as potential inhibitors of MAPK1. The study highlights that these compounds could be explored further in preclinical and clinical investigations to develop anticancer therapeutics.

A study on critical dislocation of gasket for segmental linings of shield tunnels

Correction: Aqueous spice extracts as alternative antimycotics to control highly drug resistant extensive biofilm forming clinical isolates of Candida albicans

Dynamic soil columns simulate Arctic redox biogeochemistry and carbon release during changes in water saturation

Abstract Thawing Arctic permafrost can induce hydrologic change and alter redox conditions, shifting the balance of soil organic matter (SOM) decomposition. There remains uncertainty about how soil saturation and redox transitions impact dissolved and gas phase carbon fluxes, and efforts to link hydrobiogeochemical processes to ecosystem-scale models are limited. This study evaluates SOM decomposition of Arctic tundra soils using column experiments, water chemistry measurements, microbial community analysis, and a PFLOTRAN reactive transport model. Soil columns from a thermokarst channel (TC) and an upland tundra (UC) were exposed to cycles of saturation and drainage, which controlled carbon emissions. During saturation, an outflow of dissolved organic carbon from the UC soil correlated with elevated reduced iron and decreased pH; during drainage, UC carbon dioxide fluxes were 70% higher than TC fluxes. Intermittent methane release was observed for TC, consistent with higher methanogen abundance. Slower drainage in the TC soil correlated with more subtle biogeochemical changes. PFLOTRAN simulations captured experimental trends in soil carbon fluxes, oxygen concentrations, and water contents. The model was then used to evaluate additional soil water drainage rates. This study emphasizes the importance of considering hydrologic change when evaluating and simulating SOM decomposition in dynamic Arctic tundra environments.

A pangenome analysis reveals the center of origin and evolutionary history of Phytophthora infestans and 1c clade species

We examined the evolutionary history of Phytophthora infestans and its close relatives in the 1c clade. We used whole genome sequence data from 69 isolates of Phytophthora species in the 1c clade and conducted a range of genomic analyses including nucleotide diversity evaluation, maximum likelihood trees, network assessment, time to most recent common ancestor and migration analysis. We consistently identified distinct and later divergence of the two Mexican Phytophthora species, P. mirabilis and P. ipomoeae, from P. infestans and other 1c clade species. Phytophthora infestans exhibited more recent divergence from other 1c clade species of Phytophthora from South America, P. andina and P. betacei. Speciation in the 1c clade and evolution of P. infestans occurred in the Andes. P. andina–P. betacei–P. infestans formed a species complex with indistinct species boundaries, hybridizations between the species, and short times to common ancestry. Furthermore, the distinction between modern Mexican and South American P. infestans proved less discrete, suggesting gene flow between populations over time. Admixture analysis indicated a complex relationship among these populations, hinting at potential gene flow across these regions. Historic P. infestans, collected from 1845–1889, were the first to diverge from all other P. infestans populations. Modern South American populations diverged next followed by Mexican populations which showed later ancestry. Both populations were derived from historic P. infestans. Based on the time of divergence of P. infestans from its closest relatives, P. andina and P. betacei in the Andean region, we consider the Andes to be the center of origin of P. infestans, with modern globalization contributing to admixture between P. infestans populations today from Mexico, the Andes and Europe.