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Epidemiological and spatial analysis of newly diagnosed HIV-1/AIDS patients before antiretroviral therapy in Ningxia from 2020 to 2021
The high mutability of human immunodeficiency virus type 1 (HIV-1) and the widespread use of antiretroviral drugs have rendered genetic diversity and pre-treatment drug resistance (PDR) significant obstacles to the success of antiretroviral therapy (ART). However, the research on the epidemiological and spatial distribution characteristics of PDR in Ningxia is still insufficient. A cross-sectional study utilized pre-treatment blood samples collected between 2020 and 2021 from the biorepository in May 2024. Partial pol gene sequences were obtained through plasma collection and RNA extraction. Drug resistance analysis was performed using the Stanford University HIVdb algorithm. Molecular network were constructed using Cytoscape 3.10.0. Spatial analysis and visualization were further conducted using ArcGIS10.8.1. 95 sequences were obtained, among which 7 HIV-1 genotypes were detected and CRF07_BC (67.37%, 64/95) was the predominant one. Drug resistance mutations (DRMs) were detected in 13.68%(13/95) of the sequences. The risk of PDR occurrence was higher among individuals with CRF07_BC strain types. The 24 sequences of CRF07_BC, CRF01_AE, and URF subtypes grouped into nine transmission clusters in the molecular network, with CRF07_BC showing the highest integration and clustering rates. HIV-1 infections resistant to PDR were observed in all five cities in NHAR, accompanied by cross-city transmission. Additionally, seven imported sequences were detected, comprising CRF07_BC, CRF01_AE, and C subtypes, along with three sequences of CRF55_01B with high similarity to nonlocal sequences. From 2020 to 2021, the HIV-1 diversity increased significantly in NHAR, with the prevalence of PDR reaching moderate levels and evidence of resistance transmission. The districts and counties under the jurisdiction of Yinchuan City emerged as hotspots for both pre-treatment HIV/AIDS patients and the distribution of resistant strains. It is imperative to enhance PDR testing and implement targeted interventions in key areas to minimize the emergence and dissemination of resistant virus variants.
Numerical simulation of multistable flower-shaped composite laminates with axisymmetric layups
A hydrophobic photouncaging reaction to profile the lipid droplet interactome in tissues
Most bioorthogonal photouncaging reactions preferentially occur in polar environments to accommodate biological applications in the aqueous cellular milieu. However, they are not precisely designed to chemically adapt to the diverse microenvironments of the cell. Herein, we report a hydrophobic photouncaging reaction with tailored photolytic kinetics toward solvent polarity. Structural modulations of the aminobenzoquinone-based photocage reveal the impact of cyclic ring size, steric substituent, and electronic substituent on the individual uncaging kinetics ( k H2O and k dioxane ) and polarity preference ( k dioxane / k H2O ). Rational incorporation of optimized moieties leads to up to 20.2-fold nonpolar kinetic selectivity ( k dioxane / k H2O ). Further photochemical spectroscopic characterizations and theoretical calculations together uncover the mechanism underlying the polarity-dependent uncaging kinetics. The uncaged ortho-quinone methide product bears covalent reactivity toward diverse nucleophiles of a protein revealed by tandem mass spectrometry. Finally, we demonstrate the application of such lipophilic photouncaging chemistry toward selective labeling and profiling of proteins in proximity to lipid droplets inside human fatty liver tissues. Together, this work studies the solvent polarity effects of a photouncaging reaction and chemically adapts it toward suborganelle-targeted protein proximity labeling and profiling.
Urban connected vehicle lane planning based on improved Frank Wolfe algorithm
As the new generation of information technology matures and improves, the functions of intelligent connected vehicles become more and more perfect, and the number of urban connected vehicles is also increasing. To provide an effective optimization scheme to the mixed traffic flow road network in the networked environment, the study investigates the lane planning for urban connected vehicles method. First, a lane planning for urban connected vehicles bi-level programming model is constructed. Then, the upper-level model is solved using improved whale optimization, and the lower-level model is solved using improved Frank-Wolfe algorithm. The results showed that the accuracy and recall of the proposed improved whale optimization algorithm on the Iris dataset were 95.27% and 92.65%, respectively, which were superior to traditional whale optimization algorithm, moth flame optimization algorithm, moth flame optimization algorithm combined with chaos strategy, and adaptive firefly optimization algorithm. The proposed improved Frank Wolfe algorithm can converge at around 30 iterations, with a convergence limit of around 10-4, which is superior to the traditional Frank Wolfe algorithm. The minimum total travel cost of the road system gradually decreases with the increase of the fairness index threshold. The experimental results demonstrate the effectiveness of the proposed urban connected vehicle lane planning model and solving algorithm. The research results contribute to improving the operational safety and efficiency of the road network TS, thereby improving the current traffic situation of the urban TS.
Similarities and differences between dog–human and human–human relationships
Abstract Most dog owners in Western countries regard their dogs as companions or family members, prompting extensive research on the human-animal bond. However, many studies rely on broad categories or single dimensions, such as satisfaction or attachment, which can oversimplify the complexity of these relationships. In contrast, our study employed a multifaceted approach, examining the dog-owner bond across 13 relationship scales and comparing these scales to four different types of human relationships to reveal the human-like roles of dogs within a family. Participants (N = 717) characterized their relationships with their dog and four human partners: closest kin, romantic partner, best friend, and child, using the Network of Relationships Inventory. The results showed that owners reported greater satisfaction with their dogs than with any human partner except their child. They received more Support from dogs than from any human partner except their child and experienced fewer Negative Interactions with their dogs compared to any human partner, except their best friend. Overall, the relationship with the dog provided high Companionship, opportunities for Nurturance, and minimal Negative Interactions. This may stem from the fact that the dog-human relationship features a more asymmetric power dynamic than human relationships – i.e., owners have full control over the dog’s life. Interestingly, a good relationship with a dog might also reflect the owner’s positive relationships with humans. In conclusion, the dog-human relationship exhibits characteristics of both child and best friend relationships, combining the positive aspects of the parent-child bond with the minimal negative interactions of close friendships. Characterizing the dog-owner relationship as a set of social provisions offers a valid way to evaluate relationships with dogs, providing an alternative theoretical framework to attachment theory for comparing dog-human and human-human relationships.
The POLγ Y951N patient mutation disrupts the switch between DNA synthesis and proofreading, triggering mitochondrial DNA instability
Mitochondrial DNA (mtDNA) stability, essential for cellular energy production, relies on DNA polymerase gamma (POLγ). Here, we show that the POLγ Y951N disease-causing mutation induces replication stalling and severe mtDNA depletion. However, unlike other POLγ disease-causing mutations, Y951N does not directly impair exonuclease activity and only mildly affects polymerase activity. Instead, we found that Y951N compromises the enzyme’s ability to efficiently toggle between DNA synthesis and degradation, and is thus a patient-derived mutation with impaired polymerase-exonuclease switching. These findings provide insights into the intramolecular switch when POLγ proofreads the newly synthesized DNA strand and reveal a new mechanism for causing mitochondrial DNA instability.
Design and determination of the psychometric properties of a fear of childbirth tool for Iranian adolescent mothers: An exploratory sequential mixed method study protocol
Introduction Fear of childbirth (FOC) is a crucial health issue during pregnancy and childbirth, especially among adolescent mothers. Despite emotional, physical and psychological complications of fear of childbirth, perinatal fear and anxiety have been neglected in practice. One reason is the lack of appropriate tools for timely measurement of fear in different target groups. Therefore, researchers have decided to design a fear of childbirth tool and determine its psychometric properties for Iranian teenage mothers on the basis of the cognitive vulnerability model. Methods and analysis This exploratory sequential mixed method study will be conducted in two qualitative and quantitative phases. In the qualitative phase, qualitative content analysis is performed on the basis of the cognitive vulnerability model (CVM) via interviews with pregnant adolescent women and up to 6 months after delivery. The data are analyzed according to Elo and Kyngas (2008) in three steps: preparation, organization and reporting. The quantitative phase of the study will be performed in two parts: tool design and psychometrics. We develop the FOC tool according to Waltz et al. (2017). The first step is to select a conceptual model that will be used from the results of the first phase (qualitative method). The next steps include explicating the objectives for the measure, developing the blueprint, and constructing the measure. The psychometrics of the tool will be determined via validity, including content, face and construct validity (exploratory and confirmatory factor analysis), reliability (internal consistency and relative reliability) and responsiveness. Conclusion Since there is no specific FOC tool for adolescents and the probability of this group being more vulnerable to childbirth, it is necessary to develop a valid tool specifically for adolescents to assess fear of childbirth.
Author Correction: Mobility of South America’s transcontinental drainage divide and shrinkage of the Paraná river basin linked to lithologic and geodynamic controls
Peripheral CD4 <sup>+</sup> T cells mediate the destructive effects of maternal separation on prefrontal myelination and cognitive functions
Maternal separation (MS), a chronic stress event in early life, impairs myelination in the prefrontal cortex (PFC) and leads to PFC cognitive disorders. It remains largely unclear how such deficits are mediated. Here, we show that peripheral CD4 + T cells play an essential role in mediating the destructive effects of MS on medial prefrontal cortical (mPFC) myelination and cognitive functions in mice. Offspring mice with MS experience (MS mice) exhibited an increase in CD4 + T cells and xanthine levels in peripheral blood and a severe deficit in mPFC-dependent cognitive functions such as working memory, social interaction, and anxiety/depression emotion regulation, along with a decrease in oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs) in the mPFC. These phenotypes were rescued upon treatment with the antibody neutralizing peripheral CD4 + T cells. Rag1 −/− immunodeficient mice receiving transplantation of CD4 + T cells isolated from the peripheral blood of MS mice showed similar phenotypes as observed in MS mice. Immunofluorescence staining revealed a rich expression of adenosine receptor A1 (A1) in OPCs in the mPFC, and the A1-expressing OPCs decreased in the Rag1 −/− mice receiving CD4 + T cell transplantation. The present study demonstrates a causal link between peripheral CD4 + T cells and MS-induced prefrontal cortical hypomyelination and cognitive dysfunction, and such a link is probably mediated via xanthine–adenosine receptor A1 signaling in OPCs.
Is trust a zero-sum game? What happens when institutional sources get it wrong
Trust in mainstream institutions is declining while people are increasingly turning to alternative media and conspiracy theories. Previous research has suggested that these trends may be linked, but the dynamics of trust across multiple sources has received little investigation. Is trust a neutral process, where each source is judged independently, is it a zero-sum competition, where a loss for one side is a gain for the other, or does losing trust in one source in foster a more generalized sense of distrust? Across three experimental studies (N = 2,951) we examined how people react when a source makes a serious error, testing four potential models of trust dynamics. We found that regardless of whether the outlet is mainstream, counter-mainstream, or neutral, trust drops for the erring source but does not rise for its competitors. This was the case in the context of both food regulations and COVID-19 precautions. Such a pattern suggest that each source may be judged independently of others. However, in several cases, an error made by one source led to a loss of trust in all sources, suggesting that rather than choosing sides between competing sources, people are also judging the media landscape as a whole to discern if it is feasible to find trustworthy information. However, correlational data did also find that the more people saw a source as politicized, the less they trusted that source and the more they trusted its competitors.
Machine learning based identification of suicidal ideation using non-suicidal predictors in a university mental health clinic
The “don’t eat me” signal CD47 is associated with microglial phagocytosis defects and autism-like behaviors in 16p11.2 deletion mice
Various pathological characteristics of autism spectrum disorder (ASD) stem from abnormalities in brain resident immune cells, specifically microglia, to prune unnecessary synapses or neural connections during early development. Animal models of ASD exhibit an abundance of synapses in different brain regions, which is strongly linked to the appearance of ASD behaviors. Overexpression of CD47 on neurons acts as a “don’t eat me” signal, safeguarding synapses from inappropriate pruning by microglia. Indeed, CD47 overexpression occurs in 16p11.2 deletion carriers, causing decreased synaptic phagocytosis and the manifestation of ASD characteristics. However, the role of CD47 in synaptic pruning impairment leading to ASD phenotypes in the 16p11.2 deletion mouse model is unclear. Moreover, whether blocking CD47 can alleviate ASD mice’s behavioral deficits remains unknown. Here, we demonstrate a strong link between increased CD47 expression, decreased microglia phagocytosis capacity, and increased impairment in social novelty preference in the 16p11.2 deletion mice. The reduction in microglia phagocytosis caused a rise in excitatory synapses and transmission in the prefrontal cortex of 16p11.2 deletion mice. Importantly, blocking CD47 using a specific CD47 antibody or reducing CD47 expression using a specific short hairpin RNA (shRNA) enhanced the microglia phagocytosis and reduced excitatory transmission. Reduction in CD47 expression improved social novelty preference deficits in 16p11.2 mice. These findings demonstrate that CD47 is associated with the ASD phenotypes in the 16p11.2 deletion mice and could be a promising target for the development of treatment for ASD.
The effect of enteral nutrition strategy and non-invasive ventilation on diarrhea and nutritional goals in the critically ill: A protocol for a multicentre retrospective cohort study (ENND GOALS)
Enteral nutrition (EN) has become the standard of care for nutritional support among critically ill patients. However, little is known about whether continuous delivery (CEN) or intermittent delivery (IEN) is preferable or the consequences of either strategy. This is particularly true for diarrhea, which is understudied but consistently shown to be associated with increased morbidity among critically ill patients. This is a multicenter, retrospective cohort study including critically ill patients greater than 18 years of age, admitted to the Intensive Care Unit in Hamilton, Canada, and prescribed EN for greater than 48 hours. Patients will be divided into IEN and CEN groups based on the nutritional strategy they received during their stay. The primary outcome will be the proportion of patients in each group with diarrhea during their ICU stay, diarrhea will be defined according to WHO criteria. Multivariate logistic regression will be performed to identify the role of covariates in the risk of developing diarrhea. Secondary outcomes will include caloric intake, incidence of ICU-acquired infections, including Clostridioides difficile, length of stay, and mortality. This study protocol has been approved by the Hamilton Integrated Research Ethics Board (#16453). The study findings will be disseminated at academic conferences and published in peer-reviewed journals.
Empirical validation of size effects in sub-sized tensile specimens for nuclear structural materials
QnAs with Nora Newcombe
Correction: Artificial neural network, machine learning modelling of compressive strength of recycled coarse aggregate based self-compacting concrete
Cadmium tolerance is associated with tissue-specific plasticity of metallothionein gene expression in Gammarus fossarum field populations
Abstract The metallothionein gene family codes for proteins involved in metal homeostasis and acute detoxification of non-essential toxic metal ions across the tree of life. We have previously documented increased cadmium (Cd) tolerance in field populations of the crustacean Gammarus fossarum exposed to chronic metallic contamination of geochemical origin. This tolerance is lost during maintenance of organisms in the laboratory, and is transmitted to offspring via parental effects. This study investigated whether the expression of the Cd-responsive metallothionein gene mt1 could be related to Cd-tolerance plasticity in G. fossarum. In eleven populations with different chronic Cd exposure history, we simultaneously assessed Cd-tolerance (mortality tests) and G. fossarum mt1 expression levels by RT-qPCR in the gills and caeca of adult males and in neonates. mt1 expression levels in the two organs were correlated to Cd-tolerance in field organisms and a loss of tolerance was observed in parallel with a decreased expression of mt1 in the caeca after maintenance in uncontaminated water. We also recorded a greater inducibility of mt1 expression in offspring of tolerant populations in the laboratory when re-exposed to Cd along with the bi-parental transmission of Cd-tolerance. These results suggest that the control of mt1 expression is involved in the plasticity of Cd-tolerance in gammarid populations with different histories of Cd exposure.
Rolling two-dimensional covalent organic framework (COF) sheets into one-dimensional electronic and proton-conductive nanotubes
Mimicking the interconvertible carbon allotropes of 2-dimensional (2D) graphene and 1-dimensional (1D) carbon nanotubes (CNTs), herein we report the in situ transformation of 2D π-conjugated covalent organic frameworks (COFs) sheet into 1D nanotubular structures via self-assembly the sheets at solvent interfaces. The facile “roll-sheets” self-assembly resulted in coaxial nanotubes with uniform cross-sectional diameter, which was realized for diazapyrene-based COFs but not for the corresponding pyrene COF, although both possess similar chemical structures. Upon replacing the carbon atoms at 2,7-positions of pyrene with nitrogen, contrasting optical and electronic properties were realized, reflecting the rolled structure of the conjugated 2D sheets. The nanotubes exhibited concerted electronic- and proton-conducting nature with stable conducting pathways at ambient conditions. The nitrogen centers act simultaneously as the site for charge carrier doping and proton acceptors, as evidenced by the high photo- and electrical conductivity, as well as the record proton conductivity (σ = 1.98 S cm −1 ) results. The present diazapyrene-based 1D nanotubular COF serves as a unique materials platform with electronic conduction in the wall and proton conduction in the core, respectively.
The effect of smoking on the outcomes of arthroscopic microfracture for osteochondral lesions of the talus
Background Smoking is known to negatively affect the outcomes of orthopedic procedures, but its impact on arthroscopic microfracture for osteochondral lesions of the talus (OLT) remains unclear. We aimed to compare clinical outcomes and the status of repaired cartilage following arthroscopic microfracture for small to medium-sized OLT in smokers versus nonsmokers. Methods We enrolled 239 patients (250 ankles), dividing them into smoker (56 patients, 59 ankles) and nonsmoker groups (183 patients, 191 ankles). The primary outcome measure was the FAOS (Foot and Ankle Outcome Score). The AOFAS (American Orthopaedic Foot & Ankle Society) ankle-hindfoot scale, SF-36 PCS (Short Form-36 Physical Component Summary) score, and VAS (Visual Analog Scale) for pain were included as secondary outcomes. Preoperative magnetic resonance imaging (MRI) assessed lesion size, location, and subchondral cyst presence. Postoperative cartilage repair status was evaluated using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score on 3.0-T MRI. Results The mean OLT sizes were 74.4 mm2 in smokers and 69.9 mm2 in nonsmokers on preoperative MRI. The mean age was 35.9 years in smoker group and 38.8 years in nonsmoker group (p = 0.157). The overall mean follow-up duration was 83.6 months (range, 24–217), with no significant intergroup difference (p = 0.582). There was no significant difference in primary and secondary clinical outcome variables between the two groups at the final follow-up (p > 0.05). In terms of postoperative MRI, 75 ankles (18 smokers, 57 nonsmokers) assessed repaired cartilage status and the mean total MOCART score was significantly lower in smokers (65.0, range 30.0–85.0) compared with nonsmokers (73.7, range 40.0–95.0; p = 0.027). Particularly, the smoker group had significantly lower MOCART scores for surface for repair tissue and signal intensity of the repair tissue variables, respectively (p = 0.019, p = 0.008). Conclusion Although smoker group showed worse status of repaired cartilage on postoperative MRI, the smoker group reported comparable clinical outcomes to those of the nonsmoker group following arthroscopic microfracture for small to medium-sized OLT over a mean follow-up of 7 years. However, caution should be taken in interpreting our conclusion and further larger studies are needed for robust conclusions.