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A novel entomopathogenic nematode (EPN) species, Steinernema tarimense n. sp., was isolated from soil samples collected in a Populus euphratica forest located in Yuli County within the Tarim Basin of Xinjiang, China. Integrated morphological and molecular analyses consistently place S. tarimense n. sp. within the ‘kushidai-clade’. The infective juvenile (IJ) of new species is characterized by a body length of 674–1010 μm, excretory pore located 53–80 μm from anterior end, nerve ring positioned 85–131 μm from anterior end, pharynx base situated 111–162 μm from anterior end, a tail length of 41–56 μm, and the ratios D% = 42.0–66.6, E% = 116.2–184.4, and H% = 25.5–45.1. The first-generation male of the new species is characterized by a curved spicule length of 61–89 μm, gubernaculum length of 41–58 μm, and ratios D% = 36.8–66.2, SW% = 117.0–206.1, and GS% = 54.8–82.0. Additionally, the tail of first-generation female is conoid with a minute mucron. Phylogenetic analyses of ITS, 28S, and mt12S sequences demonstrated that the three isolates of S. tarimense n. sp. are conspecific and form a sister clade to members of the ‘kushidai-clade’ including S. akhursti, S. anantnagense, S. kushidai, and S. populi. Notably, the IJs of the new species exhibited faster development at 25°C compared to other Steinernema species. This represents the first described of an indigenous EPN species from Xinjiang, suggesting its potential as a novel biocontrol agent against local pests.
Background: Deep brain stimulation (DBS) in Parkinson’s disease (PD) requires extensive trial-and-error programming, often taking over a year to optimize. An objective, rapid biomarker of stimulation success is needed. Our team developed a functional magnetic resonance imaging (fMRI)-based algorithm to identify optimal DBS settings. This study prospectively compared fMRI-guided programming with standard-of-care (SoC) clinical programming in a double-blind, crossover, non-inferiority trial. Methods: Twenty-two PD-DBS patients were prospectively enrolled for fMRI using a 30-sec DBS-ON/OFF cycling paradigm. Optimal settings were identified using our published classification algorithm. Subjects then underwent >1 year of SoC programming. Clinical improvement was assessed under SoC and fMRI-determined stimulation conditions. Results: fMRI optimization significantly reduced the time required to determine optimal settings (1.6 vs. 5.6 months, p<0.001). Unified Parkinson’s Disease Rating Scale (UPDRSIII) improved comparably with both approaches (23.8 vs. 23.6, p=0.9). Non-inferiority was demonstrated within a predefined margin of 5 points (p=0.0018). SoC led to greater tremor improvement (p=0.019), while fMRI showed greater bradykinesia improvement (p=0.040). Conclusions: This is the first prospective evaluation of an algorithm able to suggest stimulation parameters solely from the fMRI response to stimulation. It suggests that fMRI-based programming may achieve equivalent outcomes in less time than SoC, reducing patient burden while potentially enhancing bradykinesia response.
Background: Surgical robotics can minimize the discrepancy between surgical preoperative plan and postoperative execution. This work explores the performance of a supervisory-control architecture robot (8i Robotics) for autonomous pedicle instrumentation in both an open and MIS workflow in a poricne model, as well as guidance accuracy in humans. Methods: 11 porcine subjects (7 open, 4 minimally invasive) had clinical grading assessment of pedicle screw placement. 3 of the open cohort had detailed precision analysis. Post-operative CT assessed screw location. Euclidean error was calculated at screw head and screw tip and confidence ellipses generated. In two human patients, guidance accuracy was compared to existing neuro-navigation. Results: All screws where GRS A. There was no clinical difference between clinical assessment of MIS vs Open workflow. Mean tip and head Euclidean error where 2.47+/-1.25mm and 2.25+/-1.25mm respectively. Guidance was successfully obtained in both human cases. Conclusions: 100% of screws obtained satisfactory clinical grading. This demonstrates the capability of a supervisory controlled robotic pedicle screw insertion robot in both open and minimally invasive workflow. Furthermore, initial guidance was feasible in living human patients with comparable agreement to current navigation. This work demonstrates exciting promise for the future of autonomous surgical robotics.
The transition from conventional cage systems to cage-free egg production in China remains limited despite apparently increasing consumer demand for cage-free eggs. This study interviewed 15 large-scale Chinese egg producers using cages and/or cage-free systems (i.e. single-, multi-tier and free-range) to investigate the perceived challenges and opportunities during the transition. The cage farms’ scales range from 110,000 to 30 million, while the cage-free farms keep between 12,000 and 300,000 laying hens. Drawing upon the COM-B model of the Behaviour Change Wheel, this study explored how producers’ Capabilities, Opportunities, and Motivations impact decision-making processes. Key findings reveal that cage and cage-free producers considered consumer demand and profitability as primary drivers for adopting cage-free systems. While free-range producers were more confident in the market, barn system producers faced greater uncertainty due to limited engagement from corporate buyers. Moreover, these cage-free producers believed reliable certification and labelling schemes to be critical for building consumer trust and ensuring the success of cage-free operations. All the participants perceived access to sufficient land and financial resources to be essential for a successful transition. While most studies propose education as a long-term strategy to promote the growth of the cage-free egg sector, our findings are the first to highlight that engaging corporate buyers and establishing trustworthy certification schemes are the most crucial short-term interventions required to drive the development of large-scale cage-free farms and support sustained improvements in animal welfare in China.
Background: Patients with severe traumatic brain injury (TBI) are at uniquely high risk of venous thromboembolism (VTE), but the benefits of VTE prophylaxis must be weighed against the risk of intracranial hemorrhage expansion. Current guidelines are heterogenous in their recommendations for chemical VTE prophylaxis (cVTEp) in this high-risk cohort. We conducted a systematic review to identify the optimal timing of cVTEp in severe TBI patients. Methods: We executed a systematic search of the literature to identify adult severe TBI patients treated with cVTEp. Results were pooled, analyzed using random-effects models, and presented as Forest plots and odds ratios. Results: We included 21 studies representing 322,735 patients. The odds of VTE were 0.47 (95% CI: 0.37,0.60) when using the authors’ own criteria for early initiation, and the odds of VTE remained significantly decreased in subgroup analysis (<24h, <48 and <72h). Early VTEp both as defined by authors and in subgroup analysis did not significantly impact the odds of hemorrhage progression or mortality; except for initiation <48h which showed a positive impact on mortality (OR: 0.74, 95% CI: 0.63-0.87). Conclusions: This study supports early initiation of cVTEp in reducing the odds of VTE events without significantly increasing the risk of adverse events.
It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
We explore the role of targeted echocardiography as a screening tool for bicuspid aortic valve and left ventricular hypertrophy, specifically assessing the risk of missing significant cardiac findings that would otherwise be identified by comprehensive echocardiograms.
Method:
Children < 18 years at initial echocardiogram for indications of “family history of bicuspid aortic valve” and “left ventricular hypertrophy on electrocardiogram” were queried. Cardiology clinic notes and complete echocardiogram reports were reviewed for additional background histories and incidental findings. Follow-up clinic visits, if any, and management for those with incidental findings were reviewed.
Results:
Bicuspid aortic valve group included 138 patients, 71 (51%) males and mean age at comprehensive echo was 8.4 ± 4.8 years. Bicuspid aortic valve was found in 3.6%, incidental findings were found in 15 (11%), and follow-up was recommended in 4 (2.8%). Left ventricular hypertrophy group included 70 patients, 58 (83%) males and mean age at echo 10.9 ± 4.7 years. Left ventricular hypertrophy was found in 2.8%, incidental findings were found in 9 (13%), and follow-up was recommended in 2 (2.8%).
None of the follow-up group developed symptoms or required cardiac medications, exercise restrictions, or catheter or surgical-based interventions, except for one case of mild aortic root dilation who was restricted from heavy weightlifting.
Conclusion:
The risk of missing clinically important findings with targeted echocardiography that would have been identified with comprehensive echocardiography is extremely low for screening indications of isolated left ventricular hypertrophy on electrocardiogram or family history of bicuspid aortic valve, suggesting that targeted echocardiography could be an effective screening tool.
Objectives/Goals: In mice, it has been shown that loss of Cib2 (calcium and integrin-binding protein 2) results in progressive retinal disease that recapitulates many characteristics of age-related macular degeneration (AMD). This study aims to characterize transcriptional changes in the retinal pigment epithelium (RPE) that underlie this disease process. Methods/Study Population: RPE tissue samples, pooled from 2–3 mice for each biological group, were collected from Cib2-KO and wildtype (WT) mice at two (young) and eight (aged) months of age. Bulk mRNA sequencing was performed using the Illumina HiSeq 4000. Reads were aligned to the UCSC mouse reference genome and quantified using HTSeq. Significant differentially expressed genes (DEGs) between mouse genotype and age groups were assessed using DESeq. CLICK unsupervised clustering followed by gene ontology analysis was performed to identify cellular processes and molecular pathways affected by loss of Cib2 as well as age. Results/Anticipated Results: CLICK analysis revealed several functional pathways that are differentially expressed between sample groups. For example, in both young and aged mice, pathways upregulated in Cib2-KO samples included calcium signaling, RhoA signaling, and integrin signaling. Uniquely downregulated DEGs in young Cib2-KO animals were related to complement and coagulation cascades, LXR/RXR activation (related to lipid synthesis and transport), and phagosomes. Aged Cib2-KO mice displayed the most significant downregulation of genes in the phototransduction pathway, indicating temporal changes in functional pathways that correlate with disease progression. Next steps in analysis include investigating patterns in RPE- and AMD-signature gene sets that may identify molecular pathways more specific to human disease. Discussion/Significance of Impact: Many current studies investigate the role of complement activation, vesicle trafficking, and ion transport as top contributors to AMD development. We identified DEGs paralleling many of these molecular pathways in Cib2-KO mice, highlighting their potential as a model to study age-related RPE pathologies and evaluate therapeutic interventions.
Objectives/Goals: Poor visual memory and perceptual organization task performance predicts cognitive decline and is sensitive to dementia severity. No genome-wide association study (GWAS) has assessed the genomic basis of cognitive visual-spatial phenotypes. We aimed to identify common genetic variants associated with visual memory and spatial organization. Methods/Study Population: We included dementia- and stroke-free participants aged 45 years or older from up to seven cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, who performed cognitive tasks assessing delayed visual memory (e.g., Benton Visual Retention Test (BVRT, n = 10,934) and visual reproductions (VR, n = 5,527)) or spatial organization (i.e., Hooper Visual Organization Test (HVOT, n = 5,024)). Each cohort used linear regression models to relate common genetic variants imputed to the 1000 Genomes panel to each cognitive phenotype, adjusting for age, sex, population stratification, and education. Summary statistics for the BVRT were meta-analyzed using METAL. Combined GWAS was used for a joint analysis of all traits. Results/Anticipated Results: We identified a genome-wide significant variant related to BVRT performance located near the TSHZ3 gene (rs10425277, p = 6.76×10–9). TSHZ3 is important for the development and function of cortical projecting neurons and may be implicated in Alzheimer’s disease progression by repressing CASP4 transcription. Multitrait analyses, including BVRT, VR, and HVOT, identified two additional variants of interest in SMYD3 gene (rs10802275, p = 5.58×10–7) and near ZFPM2 (rs2957459, p = 2.03×10–7), both of which are overexpressed in the brain and have important implications for neurodevelopment. SMYD3 may be directly involved in synaptic dysfunction and has been shown to be upregulated in the prefrontal cortex of Alzheimer’s disease patients. Discussion/Significance of Impact: Our findings suggest that variants related to visual memory and spatial organization are involved in neurodevelopmental and degenerative pathways. This GWAS adds to the growing body of GWAS literature on the genetic basis of cognitive function. Additional analyses are underway to replicate these findings and extend functional annotation.
Mapping reviews (MRs) are crucial for identifying research gaps and enhancing evidence utilization. Despite their increasing use in health and social sciences, inconsistencies persist in both their conceptualization and reporting. This study aims to clarify the conceptual framework and gather reporting items from existing guidance and methodological studies. A comprehensive search was conducted across nine databases and 11 institutional websites, including documents up to January 2024. A total of 68 documents were included, addressing 24 MR terms and 55 definitions, with 39 documents discussing distinctions and overlaps among these terms. From the documents included, 28 reporting items were identified, covering all the steps of the process. Seven documents mentioned reporting on the title, four on the abstract, and 14 on the background. Ten methods-related items appeared in 56 documents, with the median number of documents supporting each item being 34 (interquartile range [IQR]: 27, 39). Four results-related items were mentioned in 18 documents (median: 14.5, IQR: 11.5, 16), and four discussion-related items appeared in 25 documents (median: 5.5, IQR: 3, 13). There was very little guidance about reporting conclusions, acknowledgments, author contributions, declarations of interest, and funding sources. This study proposes a draft 28-item reporting checklist for MRs and has identified terminologies and concepts used to describe MRs. These findings will first be used to inform a Delphi consensus process to develop reporting guidelines for MRs. Additionally, the checklist and definitions could be used to guide researchers in reporting high-quality MRs.
The analysis of data from experiments in economics routinely involves testing multiple null hypotheses simultaneously. These different null hypotheses arise naturally in this setting for at least three different reasons: when there are multiple outcomes of interest and it is desired to determine on which of these outcomes a treatment has an effect; when the effect of a treatment may be heterogeneous in that it varies across subgroups defined by observed characteristics and it is desired to determine for which of these subgroups a treatment has an effect; and finally when there are multiple treatments of interest and it is desired to determine which treatments have an effect relative to either the control or relative to each of the other treatments. In this paper, we provide a bootstrap-based procedure for testing these null hypotheses simultaneously using experimental data in which simple random sampling is used to assign treatment status to units. Using the general results in Romano and Wolf (Ann Stat 38:598–633, 2010), we show under weak assumptions that our procedure (1) asymptotically controls the familywise error rate—the probability of one or more false rejections—and (2) is asymptotically balanced in that the marginal probability of rejecting any true null hypothesis is approximately equal in large samples. Importantly, by incorporating information about dependence ignored in classical multiple testing procedures, such as the Bonferroni and Holm corrections, our procedure has much greater ability to detect truly false null hypotheses. In the presence of multiple treatments, we additionally show how to exploit logical restrictions across null hypotheses to further improve power. We illustrate our methodology by revisiting the study by Karlan and List (Am Econ Rev 97(5):1774–1793, 2007) of why people give to charitable causes.
Extant literature implicates the role of glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists (GLP-1RAs) on modulating alcohol-associated behaviours, with a particular emphasis of these agents on neural circuits subserving reward and appetite control. Herein, we explore the potential effects of GLP-1RAs on alcohol-associated behaviours in brain regions implicated in reward processing facilitating the repurposing of these agents for the treatment and prevention of problematic drinking. Understanding how GLP-1’s analogues interact with alcohol-related behaviours may underscore the development of therapeutic strategies for alcohol use disorder (AUD) and those with comorbid metabolic disorders.
Methods:
A systematic review was conducted, wherein relevant literature was identified through Web of Science, PubMed, and OVID (MedLINE, Embase, AMED, PsycInfo, JBI EBP) from database inception to October 27th, 2024. Preclinical and clinical studies examining the association between GLP-1RAs and alcohol-related behaviours were assessed.
Results:
Preclinical studies (n = 19) indicate that GLP-1RAs attenuate alcohol-related behaviours, with exenatide demonstrating significant dose-dependent effects in high alcohol-consuming phenotypes. Semaglutide and liraglutide are associated with reduced alcohol intake, though their effects were often transient. In human studies (n = 2) with AUD, semaglutide significantly reduced alcohol consumption, while exenatide showed mixed results, with reductions in alcohol drinking within high BMI subpopulations.
Discussion:
Extant preclinical and clinical literature provides preliminary support for the potential therapeutic role of GLP-1RAs in attenuating alcohol consumption and preference. There is a need for large well controlled studies evaluating the effect of GLP-1RAs as a treatment strategy for behavioural modifications in individuals living with alcohol use disorder.
Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) administration has been associated with neuroproliferative effects and modulatory effects in neuronal pathways. Herein, we conducted a comprehensive synthesis of the effects of GLP-1 and GLP-1 RAs on neurogenesis.
Methods:
We examined studies that investigate changes in neurogenesis mediated by GLP-1 and GLP-1 RA administration in both human and animal populations. Relevant articles were retrieved through OVID (MedLine, Embase, AMED, PsychINFO, JBI EBP Database), PubMed, and Web of Science from database inception to July 2nd. Primary studies investigating the role of GLP-1 and GLP-1 RAs on neurogenesis were included for analysis.
Results:
GLP-1 and GLP-1 RAs (i.e. exenatide, geniposide, liraglutide, lixisenatide, and semaglutide), increased neurogenesis within the dentate gyrus, hippocampus, olfactory bulb, and the medial striatum in animal models. Additionally, GLP-1 and GLP-1 RAs were associated with modulating changes in multiple apoptotic pathways and upregulating survival pathways.
Discussion:
GLP-1 and GLP-1 RAs are positively associated with neurogenesis. This effect may have translational implications insofar as disparate mental disorders that are characterised by neurogenesis defects (e.g. depressive disorders and neurocognitive disorders) may be benefitted by these agents.
We study the last exit time that a spectrally negative Lévy process is below zero until it reaches a positive level b, denoted by $g_{\tau_b^+}$. We generalize the results of the infinite-horizon last exit time explored by Chiu and Yin (2005) by incorporating a random horizon $\tau_b^+$, which represents the first passage time above b. We derive an explicit expression for the joint Laplace transform of $g_{\tau_b^+}$ and $\tau_b^+$ by utilizing a hybrid observation scheme approach proposed by Li, Willmot, and Wong (2018). We further study the optimal prediction of $g_{\tau_b^+}$ in the $L_1$ sense, and find that the optimal stopping time is the first passage time above a level $y_b^{\ast}$, with an explicit characterization of the stopping boundary $y_b^{\ast}$. As examples, Brownian motion with drift and the Cramér–Lundberg model with exponential jumps are considered.
This paper considers the guidance issue for attackers against aircraft with active defense in a two-on-two engagement, which includes an attacker, a protector, a defender and a target. A cooperative line-of-sight guidance scheme with prescribed performance and input saturation is proposed utilising the sliding mode control and line-of-sight guidance theories, which guarantees that the attacker is able to capture the target with the assistance of the protector remaining on the line-of-sight between the defender and the attacker in order to intercept the defender. A fixed-time prescribed performance function and first-order anti-saturation auxiliary variable are designed in the game guidance strategy to constrain the overshoot of the guidance variable and satisfy the requirement of an overload manoeuver. The proposed guidance strategy alleviates the influence of external disturbance by implementing a fixed-time observer and the chattering phenomenon caused by the sign function. Finally, nonlinear numerical simulations verify the cooperative guidance strategies.
Sleep value is the relative worth individuals assign to sleep. We previously found that individual differences in several sleep value subfactors relate to demographic, health and sleep variables. Given the pivotal role values play in health behavior and the positive association between sleep value and sleep disturbance, individual differences in sleep value may influence vulnerability/resilience to sleep and circadian disturbance. This survey study (N = 455) aimed to establish the latent factor structure of sleep value and identify whether sleep value profiles relate to demographic and sleep characteristics. Factor analysis on the Sleep Valuation Item Bank 2.0 identified five factors (wanting, prioritizing, devaluing, appreciating and preferring). Latent profile analyses revealed five distinct sleep value profiles (unconcerned, appreciative, devalue, ambivalent priority and concerned). Depression, sleep disturbance and sleep-related impairment were highest among those who highly value sleep (concerned profile) and lowest among those who neither value nor devalue sleep (unconcerned profile). Findings suggest sleep value is a complex aspect of sleep health rather than a “more is better” construct and highlight that individual differences in sleep value profiles may be associated with vulnerability/resilience to sleep disturbance.
The clinical high risk for psychosis (CHR-p) syndrome enables early identification of individuals at risk of schizophrenia and related disorders. We differentiate between the stigma associated with the at-risk identification itself (‘labelling-related’ stigma) versus stigma attributed to experiencing mental health symptoms (‘symptom-related’ stigma) and examine their relationships with key psychosocial variables.
Aims
We compare labelling- and symptom-related stigma in rates of endorsement and associations with self-esteem, social support loss and quality of life.
Method
We assessed stigma domains of shame-related emotions, secrecy and experienced discrimination for both types of stigma. Individuals at CHR-p were recruited across three sites (N = 150); primary analyses included those who endorsed awareness of psychosis risk (n = 113). Paired-sample t-tests examined differences in labelling- versus symptom-related stigma; regressions examined associations with psychosocial variables, controlling for covariates, including CHR-p symptoms.
Results
Respondents reported greater symptom-related shame, but more labelling-related secrecy. Of the nine significant associations between stigma and psychosocial variables, eight were attributable to symptom-related stigma, even after adjusting for CHR-p symptoms.
Conclusions
Stigma attributed to symptoms had a stronger negative association with psychosocial variables than did labelling-related stigma among individuals recently identified as CHR-p. That secrecy related to the CHR-p designation was greater than its symptom-related counterpart suggests that labelling-related stigma may still be problematic for some CHR-p participants. To optimise this pivotal early intervention effort, interventions should address the holistic ‘stigmatising experience’ of having symptoms, namely any harmful reactions received as well as participants’ socially influenced concerns about what their experiences mean, in addition to the symptoms themselves.
Many psychotropic drugs are highly associated with related weight gain. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established anti-obesity and glucose-lowering agents. Preliminary evidence also indicates they are fit for purpose in mitigating psychotropic drug-related weight gain (PDWG). This systematic review aims to synthesize the extant evidence from randomized controlled trials (RCTs) on the effects of GLP-1RAs on weight change in persons experiencing PDWG.
Methods
Online databases (ie, PubMed, OVID Medline, Google Scholar) were searched to identify relevant studies from inception to January 1, 2024. Articles were screened by title, abstract, and full-text by three independent reviewers against inclusion and exclusion criteria.
Results
We identified six studies with participants aged ≥18 (n=374) that were eligible for inclusion in our systematic review. Most studies reported a significant and clinically meaningful effect of GLP-1RAs on anthropometrics and/or metabolics. All RCTs replicated the finding of modest or greater effects of GLP-1RAs; the most studied agents were liraglutide and exenatide. There was insufficient literature to conduct a meta-analysis.
Conclusion
Evidence suggests that GLP-1RAs are effective in mitigating weight gain in persons prescribed psychiatric medication. It is hypothesized that GLP-1RAs may moderate weight change in persons prescribed psychiatric medication through direct effects on metabolism and cognitive processes implicated in hunger/satiety. Future studies should aim to explore the long-term safety, tolerability, and efficacy profiles of various GLP-1RAs in the treatment and prevention of abnormal weight and metabolic homeostasis in psychiatric populations.