Browse Articles

E-cigarette usage and mental health among undergraduate medical and health sciences students

A Shared Threat-Anticipation Circuit Is Dynamically Engaged at Different Moments by Certain and Uncertain Threat

Temporal dynamics play a central role in models of emotion: “fear” is widely conceptualized as a phasic response to certain-and-imminent danger, whereas “anxiety” is a sustained response to uncertain-or-distal harm. Yet the underlying neurobiology remains contentious. Leveraging a translationally relevant fMRI paradigm and theory-driven modeling approach in 220 adult humans, we demonstrate that certain- and uncertain-threat anticipation recruit a shared circuit that encompasses the central extended amygdala (EAc), periaqueductal gray, midcingulate, and anterior insula. This circuit exhibits persistently elevated activation when threat is uncertain and distal and transient bursts of activation just before certain encounters with threat. Although there is agreement that the EAc plays a critical role in orchestrating responses to threat, confusion persists about the respective contributions of its major subdivisions, the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce). Here we used anatomical regions of interest to demonstrate that the BST and Ce exhibit statistically indistinguishable threat dynamics. Both regions exhibited activation dynamics that run counter to popular models, with the Ce (and BST) showing sustained responses to uncertain-and-distal threat and the BST (and Ce) showing phasic responses to certain-and-imminent threat. For many scientists, feelings are the hallmark of fear and anxiety. Here we used an independently validated multivoxel brain “signature” to covertly probe the moment-by-moment dynamics of anticipatory distress for the first time. Results mirrored the dynamics of neural activation. These observations provide fresh insights into the neurobiology of threat-elicited emotions and set the stage for more ambitious clinical and mechanistic research.

Elevated mitochondrial membrane potential is a therapeutic vulnerability in Dnmt3a-mutant clonal hematopoiesis

Abstract The competitive advantage of mutant hematopoietic stem and progenitor cells (HSPCs) underlies clonal hematopoiesis (CH). Drivers of CH include aging and inflammation; however, how CH-mutant cells gain a selective advantage in these contexts is an unresolved question. Using a murine model of CH (Dnmt3a R878H/+), we discover that mutant HSPCs sustain elevated mitochondrial respiration which is associated with their resistance to aging-related changes in the bone marrow microenvironment. Mutant HSPCs have DNA hypomethylation and increased expression of oxidative phosphorylation gene signatures, increased functional oxidative phosphorylation capacity, high mitochondrial membrane potential (Δψm), and greater dependence on mitochondrial respiration compared to wild-type HSPCs. Exploiting the elevated Δψm of mutant HSPCs, long-chain alkyl-TPP molecules (MitoQ, d-TPP) selectively accumulate in the mitochondria and cause reduced mitochondrial respiration, mitochondrial-driven apoptosis and ablate the competitive advantage of HSPCs ex vivo and in vivo in aged recipient mice. Further, MitoQ targets elevated mitochondrial respiration and the selective advantage of human DNMT3A-knockdown HSPCs, supporting species conservation. These data suggest that mitochondrial activity is a targetable mechanism by which CH-mutant HSPCs gain a selective advantage over wild-type HSPCs.

A novel decision ensemble framework: Attention-customized BiLSTM and XGBoost for speculative stock price forecasting

Forecasting speculative stock prices is essential for effective investment risk management and requires innovative algorithms. However, the speculative nature, volatility, and complex sequential dependencies within financial markets present inherent challenges that necessitate advanced techniques. In this regard, a novel framework, ACB-XDE (Attention-Customized BiLSTM-XGB Decision Ensemble), is proposed for predicting the daily closing price of speculative stock Bitcoin-USD (BTC-USD). The proposed ACB-XDE framework integrates the learning capabilities of a customized Bi-directional Long Short-Term Memory (BiLSTM) model with a novel attention mechanism and the XGBoost algorithm. The customized BiLSTM leverages its learning capabilities to capture complex sequential dependencies and speculative market trends. Meanwhile, the new attention mechanism dynamically assigns weights to influential features based on volatility patterns, thereby enhancing interpretability and optimizing effective cost measures and volatility forecasting. Moreover, XGBoost handles nonlinear relationships and contributes to the proposed ACB-XDE framework’s robustness. Furthermore, the error reciprocal method improves predictions by iteratively adjusting model weights based on the difference between theoretical expectations and actual errors in the individual attention-customized BiLSTM and XGBoost models. Finally, the predictions from both the XGBoost and attention-customized BiLSTM models are concatenated to create a varied prediction space, which is then fed into the ensemble regression framework to improve the generalization capabilities of the proposed ACB-XDE framework. Empirical validation of the proposed ACB-XDE framework involves its application to the volatile Bitcoin market, utilizing a dataset sourced from Yahoo Finance (Bitcoin-USD, 10/01/2014 to 01/08/2023). The proposed ACB-XDE framework outperforms state-of-the-art models with a MAPE of 0.37%, MAE of 84.40, and RMSE of 106.14. This represents improvements of approximately 27.45%, 53.32%, and 38.59% in MAPE, MAE, and RMSE respectively, over the best-performing attention-BiLSTM. The proposed ACB-XDE framework presents a technique for informed decision-making in dynamic financial landscapes and demonstrates effectiveness in handling the complexities of BTC-USD data.

A case-control study on the role of carbonic anhydrase autoantibodies in the pathogenesis and diagnosis of fibromyalgia

Mouse MRE11-RAD50-NBS1 is needed to start and extend meiotic DNA end resection

Abstract Nucleolytic resection of DNA ends is critical for homologous recombination, but its mechanism is not fully understood, particularly in mammalian meiosis. Here we examine roles of the conserved MRN complex (MRE11, RAD50, and NBS1) through genome-wide analysis of meiotic resection during spermatogenesis in mice with various MRN mutations, including several that cause chromosomal instability in humans. Meiotic DSBs form at elevated levels but remain unresected if Mre11 is conditionally deleted, thus MRN is required for both resection initiation and regulation of DSB numbers. Resection lengths are reduced to varying degrees in MRN hypomorphs or if MRE11 nuclease activity is attenuated in a conditional nuclease-dead Mre11 model. These findings unexpectedly establish that MRN is needed for longer-range extension of resection beyond that carried out by the orthologous proteins in budding yeast meiosis. Finally, resection defects are additively worsened by combining MRN and Exo1 mutations, and mice that are unable to initiate resection or have greatly curtailed resection lengths experience catastrophic spermatogenic failure. Our results elucidate MRN roles in meiotic DSB end processing and establish the importance of resection for mammalian meiosis.

Experimental study on the effect of Ivermectin on cattle dung faunas in Eastern Ethiopia

An experimental investigation was conducted from December 2023 to June 2024 at the beef farm of Haramaya University. The bulls were divided into two groups: one group received ivermectin treatment, while the other acted as a control. The SUMIVER brand of ivermectin was administered subcutaneously at 1 ml per 50 kg of body weight. Dung samples from both groups were collected and prepared for analysis at five-day intervals during the eighth sampling period. The results were measured, documented, and analyzed both qualitatively and quantitatively. All data were entered and analyzed using an independent t-test with the STATA-14 software. In the qualitative assessment, no dipteran larvae or pupae were detected in the dung samples, except during the eighth round. However, various species of invertebrates were attracted to the freshly managed dung, resulting in a higher visitation rate in the control group compared to the experimental group. In the initial weeks of the study, the presence of ivermectin residues affected the dung beetle population. Conversely, the treated dung showed a significant infestation of termites. After several weeks, both groups of dung pats were invaded by ants, with the control group experiencing infestation first. These findings suggest that ivermectin residues released into the environment through cattle dung can influence negatively plant germination, dung fauna, and soil fertility. Therefore, it is crucial for veterinarians to be knowledgeable about the environmental side effects of ivermectin and to offer guidance to livestock owners.

A stress-tolerant strain Rhodococcus sp. WH103 was isolated and co-immobilized to more efficiently degrade phenazine-1-carboxylic acid

Trivalent Phospha-Brook rearrangement enabled practical deoxygenative phosphonylation of carbonyls

Optimal control analysis for the transmission of Nipah infection with imperfect vaccination

This paper presents an innovative mathematical model for assessing the dynamics and optimal control of Nipah virus (NiV) with imperfect vaccination. The model formulation considers transmissions through contaminated food and human-to-human contacts. It also incorporates the potential virus transmission through contact with a deceased body infected with NiV. Initially, the NiV model is assessed theoretically, identifying three distinct equilibrium states: the NiV-endemic equilibrium state, the NiV-free equilibrium state, and the equilibrium state involving infected flying foxes. Furthermore, the stability results of the model in the case of constant controls are thoroughly analyzed at the NiV-free equilibrium. Some of the parameters of the model are estimated based on the infected cases documented in Bangladesh from 2001 to 2017. We further perform sensitivity analysis to determine the most influential parameters and formulate effective time-dependent controls. Numerical simulations indicate the optimal course of action for eradicating the disease and provide a comparative analysis of controlling the infection under constant and time-varying interventions. The simulation confirms that the implementation of time-varying interventions is effective in minimizing disease incidence.

BiAttentionNet: a dual-branch automatic driving image segmentation network integrating spatial and channel attention mechanisms

Fluorescent pyridine phosphonium salts via transmutation of metallabenzenes

Factors associated with the survival of adults with COVID-19 using a high-flow nasal cannula in a tertiary hospital in northern Peru during the second wave of the pandemic

Objectives To identify factors associated with survival in patients admitted to the intensive care unit (ICU) for COVID-19 who used high-flow nasal cannula (HFNC) in a tertiary hospital in northern Peru during March to May 2021. Methodology A retrospective observational cohort study was carried out, including medical records selected according to established inclusion criteria. The dependent variable was survival, measured in days from admission to hospital discharge or death. Factors associated with survival related to demographic, clinical, laboratory, and imaging characteristics were investigated, as well as treatment-related parameters and variables associated with the use of HFNC. Hazard ratios (HR) were estimated to identify independent risk factors associated with survival. Results Of 154 patients, the mean age was 58.29 years. The most frequent comorbidities were arterial hypertension (29.2%), diabetes mellitus (20.6%), and obesity (17.4%). The median time of HFNC use was 5 days (interquartile range: 3–9 days). It was found that 32.2% of the patients required mechanical ventilation, and 51.6% died. The mean time of mechanical ventilation use was 15.1 ± 13.3 days. Survival was 97.5% at 48 hours, 85% at 7 days, 62% at 14 days, and 16.3% at the end of the study. Variables decreasing survival in patients with COVID-19 who were users of NFVC were age ≥ 60 years (HR = 2.23; 95% CI: 1.21–4.08), presence of arterial hypertension (HR = 1.87; 95% CI: 1.01–3.45), increased work of breathing on hospital admission (HR = 2.38; 95% CI: 1.31–4.35), and a ROX index (iROX) < 3.85 (HR = 1.71; 95% CI: 1.01–2.93). Conclusions Factors associated with survival were arterial hypertension and iROX < 3.85 with a mortality hazard of 1.5 times, age older than 60 years, and respiratory effort scale at admission WOB ≥ 4 points with more than twice the mortality hazard. The results of this study highlight the importance of early and accurate assessment of risk factors in patients with COVID-19 who use HFNC. Identifying these factors can help clinicians make more informed decisions and prioritize interventions that could potentially improve survival in this group of patients.

Defect detection method based on sparse scanning with laser ultrasonics

Inflammatory conditions shape phenotypic and functional characteristics of lung-resident memory T cells in mice

Abstract Lung tissue-resident memory T cells (TRM) are critical for the local control of respiratory tract infections caused by influenza A viruses (IAV). Here we compare TRM populations induced by intranasal adenoviral vector vaccines encoding hemagglutinin and nucleoprotein (NP) with those induced by an H1N1 infection in BALB/c mice. While vaccine-induced TRM express high levels of CD103 and persist longer in the lung parenchyma, short-lived, H1N1-induced TRM have a transcriptome associated with higher cytotoxic potential and distinct transcriptional profile as shown by single-cell RNA sequencing. In both the vaccine and H1N1 groups, NP-specific CD8+ T cells expand during heterologous influenza virus infection and protect the mice from disease. Meanwhile, lung inflammation in response to an infection with unrelated respiratory syncytial virus do not influence the fate of pre-existing TRM. Our preclinical work thus confirms that inflammatory conditions in the tissue shape the phenotypic and functional characteristics of TRM to serve relevant informations for optimizing mucosal vaccines.

Protocol for a prospective cohort study on congenital heart disease in neonates across varied altitudes in Sichuan province, China

Congenital heart disease (CHD) is the most prevalent congenital disorder, contributing significantly to neonate mortality. Despite advances in diagnosis and treatment, the incidence and risk factors of CHD remain underexplored, particularly in regions with varied altitudes. Sichuan Province, China, with its diverse topography and altitudes, provides a unique opportunity to investigate the epidemiology of CHD across different environmental settings. This study aims to explore the incidence, subtypes, and risk factors of CHD in neonates across high, middle, and low-altitude regions of Sichuan Province. It also seeks to assess the effectiveness of the Sichuan Province Newborn CHD Free Screening Project, the impact of CHD on family economics and child development, and to provide data-driven recommendations for improving CHD prevention and control measures. We will conduct a multicenter, prospective cohort study involving neonates with positive CHD screening results and their families, recruited from three cities representing different altitude levels: Aba Tibetan and Qiang Autonomous Prefecture, Mianyang City, and Guangyuan City. Data collection will include birth characteristics, CHD screening outcomes, parental and gestational histories, and blood samples for genetic analysis. The study will monitor treatment outcomes, economic impact, and the growth and development of the children over time. This study will provide critical insights into the epidemiology of CHD in Sichuan Province, particularly in relation to altitude. The results will help optimize CHD screening and management programs, ultimately improving outcomes for affected children and their families.

The role of the hippocampus and SLC39A8 in chronic musculoskeletal pain-induced dementia: a Mendelian randomization study

A2A-Positive Neurons in the Nucleus Accumbens Core Regulate Effort Exertion

Previous work has implicated the nucleus accumbens (NAc) in the regulation of effort, defined as the amount of work an animal is willing to perform for a given reward, but little is known about the specific contributions of neuronal populations within the NAc to effort regulation. In this study, using male and female mice, we examined the contributions of direct pathway and indirect pathway neurons in the NAc core using an operant effort regulation task, in which the effort requirement is the number of lever presses needed for earning a food reward. Using optogenetics, we manipulated the activity of direct pathway spiny projection neurons (SPNs; dopamine D1-like, D1+) and indirect pathway SPNs (iSPNs; adenosine 2A receptor, A2A+). Activating dSPNs reduced lever pressing regardless of the effort requirement, as it elicited gnawing, a competing consummatory behavior. On the other hand, activating iSPNs in the NAc core (but not in the shell) reduced lever pressing in an effort-dependent manner: stimulation-induced reduction in performance was greater at higher press-to-reward ratio requirements. In contrast, optogenetically inhibiting NAc core iSPN output resulted in increased levels of effort exertion. Our results show that the indirect pathway output from the NAc core can bidirectionally regulate effort exertion.

High kinetic inductance cavity arrays for compact band engineering and topology-based disorder meters

Abstract Superconducting microwave metamaterials offer enormous potential for quantum optics and information science, enabling the development of advanced quantum technologies for sensing and amplification. In the context of circuit quantum electrodynamics, such metamaterials can be implemented as coupled cavity arrays (CCAs). In the continuous effort to miniaturize quantum devices for increasing scalability, minimizing the footprint of CCAs while preserving low disorder becomes paramount. In this work, we present a compact CCA architecture using superconducting NbN thin films manifesting high kinetic inductance. The latter enables high-impedance CCA (~1.5 kΩ), while reducing the resonator footprint. We demonstrate its versatility and scalability by engineering one-dimensional CCAs with up to 100 resonators and with structures that exhibit multiple bandgaps. Additionally, we quantitatively investigate disorder in the CCAs using symmetry-protected topological SSH edge modes, from which we extract a resonator frequency scattering of $$0.2{2}_{-0.03}^{+0.04}\%$$ 0.2 2 − 0.03 + 0.04 % . Our platform opens up exciting prospects for analog quantum simulations of many-body physics with ultrastrongly coupled emitters.

Evaluation and Characterization of Acute respiratory distress syndrome in tree shrews through TMT proteomic method

Acute respiratory distress syndrome (ARDS), a common cause of acute fatal respiratory, is characterized by severe inflammatory lung injury as well as hallmarks of increased pulmonary vascular permeability, neutrophil infiltration, and macrophage accumulation. Tree shrew, a squirrel-like small animal model, has been confirmed to have more similar traits to human ARDS with one-hit intratracheal instillation of LPS in our previous study. In this study, we characterized protein profile changes induced by intranasal LPS challenge in the tree shrew model through tandem mass tag (TMT)-based quantitative proteomics and type II alveolar epithelial cells through pathological analysis. In total, 4070 proteins (p <  0.05) were identified from lung tissues of the LPS-induced group and PBS group. Among the differential expression proteins (DEPs) detected by t-test (≥|1.5-fold|), 529 DEPs were identified, of which 304 were upregulated, and 225 were downregulated. The most important pathways involved in the process of ARDS had been identified by enrichment analysis: oxidative stress, apoptosis, inflammatory responses, and vascular endothelial injury. In addition, proteins have been reported in animal models or clinical patients also detail investigated for further analysis, such as ceruloplasmin (CP), hemopexin (HPX), sphingosine kinase 1 (SphK1), lactotransferrin (LTF), and myeloperoxidase (MPO) were upregulated in induced tissues and confirmed by western blot analysis. Overall, this study not only reveals a comprehensive proteomic analysis of the ARDS tree shrew model but also provides novel insights into multi-pathways responses induced by the LPS challenge of tree shrews. We highlight shared and unique proteomic changes in the lungs of ARDS tree shrews and identify novel pathways for acute lung injury, which may promote the model into basic research and translational research.