RESUMEN

The pseudorabies virus (PRV) causes severe and fatal acute respiratory disease in pigs. During PRV proliferation, the enzyme deoxyuridine 5'-triphosphate nucleotide hydrolase (dUTPase) plays a pivotal role in maintaining a low dUTP/dTTP ratio, thereby ensuring the accuracy of viral DNA replication. However, its structure and catalytic mechanisms have not been fully elucidated. Here, we report the crystal structure of PRV dUTPase at a 2.24 Šresolution and demonstrate an unprecedented dimeric architecture, with a conserved enzyme activity center of the herpesvirus family. The enzyme activity center is located in a cavity between the two domains, forming a pocket for binding substrate dUMP and magnesium ions. Remarkably, the exquisite interface of the dimer is primarily composed of four antiparallel ß-sheets, which form 11 hydrogen bonds between the residues P33-V36 and R242-A248 to maintain protein stability. To the best of our knowledge, this is the first report demonstrating that dUTPase exists as a dimer in the herpesvirus family. These findings not only present a novel fold dimeric structure but also deepen the scope of our comprehension of structural diversity in dUTPase family.

RESUMEN

Extracellular vesicles (EVs) are nanovesicles containing bioactive molecules including proteins, nucleic acids and lipids that mediate intercellular and inter-organ communications, holding promise as potential therapeutics for multiple diseases. Adipose tissue (AT) serves as a dynamically distributed energy storage organ throughout the body, whose accumulation leads to obesity, a condition characterized by infiltration with abundant immune cells. Emerging evidence has illustrated that EVs secreted by AT are the novel class of adipokines that regulate the homeostasis between AT and peripheral organs. However, most of the studies focused on the investigations of EVs derived from adipocytes or adipose-derived stem cells (ADSCs), the summarization of functions in cellular and inter-organ crosstalk of EVs directly derived from adipose tissue (AT-EVs) are still limited. Here, we provide a systemic summary on the key components and functions of EVs derived from healthy adipose tissue, showing their significance on the tissue recovery and metabolic homeostasis regulation. Also, we discuss the harmful influences of EVs derived from obese adipose tissue on the distal organs. Furthermore, we elucidate the potential applications and constraints of EVs from healthy patients lipoaspirates as therapeutic agents, highlighting the potential of AT-EVs as a valuable biological material with broad prospects for future clinical use.

Asunto(s)

Tejido Adiposo , Vesículas Extracelulares , Obesidad , Humanos , Vesículas Extracelulares/metabolismo , Obesidad/metabolismo , Obesidad/patología , Tejido Adiposo/metabolismo , Animales , Adipocitos/metabolismo , Adipoquinas/metabolismo

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The reconstruction of indoor scenes from multi-view RGB images is challenging due to the coexistence of flat and texture-less regions alongside delicate and fine-grained regions. Recent methods leverage neural radiance fields aided by predicted surface normal priors to recover the scene geometry. These methods excel in producing complete and smooth results for floor and wall areas. However, they struggle to capture complex surfaces with high-frequency structures due to the inadequate neural representation and the inaccurately predicted normal priors. This work aims to reconstruct high-fidelity surfaces with fine-grained details by addressing the above limitations. To improve the capacity of the implicit representation, we propose a hybrid architecture to represent low-frequency and high-frequency regions separately. To enhance the normal priors, we introduce a simple yet effective image sharpening and denoising technique, coupled with a network that estimates the pixel-wise uncertainty of the predicted surface normal vectors. Identifying such uncertainty can prevent our model from being misled by unreliable surface normal supervisions that hinder the accurate reconstruction of intricate geometries. Experiments on the benchmark datasets show that our method outperforms existing methods in terms of reconstruction quality. Furthermore, the proposed method also generalizes well to real-world indoor scenarios captured by our hand-held mobile phones. Our code is publicly available at: https://github.com/yec22/Fine-Grained-Indoor-Recon.

RESUMEN

Background: A considerable proportion of hypertensive patients may experience lacunar infarction. Therefore, early identification of the risk for lacunar infarction in hypertensive patients is particularly important. This study aimed to develop and validate a concise nomogram for predicting lacunar infarction in hypertensive patients. Methods: Retrospectively analyzed the clinical data of 314 patients with accurate history of hypertension in the Second Affiliated Hospital of Wannan Medical College from January 2021 to December 2022. All the patients were randomly assigned to the training set (n=220) and the validation set (n=94) with 7:3. The diagnosis of lacunar infarction in patients was confirmed using cranial CT or MRI. The independent risk factors of lacunar infarction were determined by Least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression analysis. The nomogram was built based on the independent risk factors. The nomogram's discrimination, calibration, and clinical usefulness were evaluated by receiver operating characteristics (ROC) curve, calibration curve, and decision curve analysis (DCA) analysis, respectively. Results: The incidence of lacunar infarction was 34.50% and 33.00% in the training and validation sets, respectively. Five independent predictors were made up of the nomogram, including age (OR=1.142, 95% CI: 1.089-1.198, P<0.001), diabetes mellitus (OR=3.058, 95% CI: 1.396-6.697, P=0.005), atrial fibrillation (OR=3.103, 95% CI: 1.328-7.250, P=0.009), duration of hypertension (OR=1.130, 95% CI: 1.045-1.222, P=0.002), and low-density lipoprotein (OR=2.147, 95% CI: 1.250-3.688, P=0.006). The discrimination with area under the curve (AUC) was 0.847 (95% CI: 0.789-0.905) in the training set and was a slight increase to 0.907 (95% CI: 0.838-0.976) in the validation set. The calibration curve showed high coherence between the predicted and actual probability of lacunar infarction. Moreover, the DCA analysis indicated that the nomogram had a higher overall net benefit of the threshold probability range in both two sets. Conclusion: Age, diabetes mellitus, atrial fibrillation, duration of hypertension, and low-density lipoprotein were significant predictors of lacunar infarction in hypertensive patients. The nomogram based on the clinical data was constructed, which was a useful visualized tool for clinicians to assess the risk of the lacunar infarction in hypertensive patients.

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We conducted a longitudinal cohort study of SARS-CoV-2 and influenza rates in childcare centers and schools in Wuxi, China, collecting 1,760 environmental samples and 9,214 throat swabs from 593 students (regardless of symptoms) in weekly collections during February-June 2023. We estimated a cumulative infection rate of 124.8 (74 episodes)/1,000 persons for SARS-CoV-2 and 128.2 (76 episodes)/1,000 persons for influenza. The highest SARS-CoV-2 infection rate was in persons 18 years of age, and for influenza, in children 4 years of age. The asymptomatic proportion of SARS-CoV-2 was 59.6% and 66.7% for influenza; SARS-CoV-2 symptomatic proportion was lower in 16-18-year-olds than in 4-6-year-olds. Only samples from frequently touched surface tested positive for SARS-CoV-2 (4/1,052) and influenza (1/1,052). We found asynchronous circulation patterns of SARS-CoV-2 and influenza, similar to trends in national sentinel surveillance. The results support vaccination among pediatric populations and other interventions, such as environmental disinfection in educational settings.

Asunto(s)

COVID-19 , Gripe Humana , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/virología , Niño , Gripe Humana/epidemiología , Gripe Humana/virología , Adolescente , China/epidemiología , Preescolar , Masculino , Femenino , Estudios Longitudinales , Lactante

RESUMEN

BACKGROUND: Catheter-related thrombosis (CRT) is a thrombotic complication associated with using central venous catheters (CVCs). Although risk factors for CRT were identified in children, no nomograms or predictive tools are available for the pediatric population with CVCs. This study aimed to develop and validate a prediction model of asymptomatic CRT in children with CVCs. METHODS: This retrospective observational study included consecutive pediatric patients who admitted to the Children's Hospital Zhejiang University School of Medicine and received CVCs between October and December 2021. RESULTS: This study included 669 patients, 553 (314 males, aged 22.00 [0.36, 180.00] months, 62 with CRT) were in the training set, and 116 (62 males, aged 15.00 [1.13, 156.00] months, 16 with CRT) were in the validation set. Multivariate logistic regression showed that a catheter time of 0-3 days (OR = 0.201, 95%CI: 0.081-0.497, P = 0.001), catheter time of 4-7 days (OR = 0.412, 95%CI: 0.176-0.964, P = 0.041), male (OR = 3.976, 95%CI: 1.864-4.483, P < 0.001), congenital heart diseases (OR = 0.277, 95%CI: 0.078-0.987, P = 0.048), postoperative (OR = 0.161, 95%CI: 0.072-0.360, P < 0.001), and femoral CVC (OR = 2.451, 95%CI: 1.129-5.318, P = 0.002) were independently associated with CRT. The nomogram incorporating these variables showed relatively good discrimination (AUC = 0.77, 95%CI: [0.65, 0.90]) and calibration abilities in the validation set, and the decision curve analysis (DCA) yielded a clinical net benefit. CONCLUSION: A prediction model for CRT in children with CVC was established based on catheter time, sex, diseases, postoperative, and catheter vein. The nomogram based on logistic regression model showed favorable predictive performance.

Asunto(s)

Catéteres Venosos Centrales , Nomogramas , Humanos , Masculino , Estudios Retrospectivos , Femenino , Niño , Adolescente , Lactante , Preescolar , Catéteres Venosos Centrales/efectos adversos , Factores de Riesgo , Trombosis/etiología , Trombosis/diagnóstico , Cateterismo Venoso Central/efectos adversos , Recién Nacido , Modelos Logísticos

RESUMEN

Background: Multidrug-resistant Gram-negative bacteria (MDR-GNB) are becoming increasingly common around the world, with carbapenems frequently serving as a last resort but being threatened by the growing incidence of carbapenemase-producing bacteria. Ceftazidime-avibactam (CAZ/AVI) is a potential agent against MDR-GNB but with limited clinical experience, particularly in critically ill immunosuppressed children. Methods: This study analyzed the use of CAZ/AVI as salvage treatment in severely infected immunosuppressed children from September 2019 to July 2022. Patients with confirmed GNB infection who received CAZ/AVI were matched with patients who received other antibiotics. Results: Twenty-five critically ill immunosuppressed children treated with CAZ/AVI were included. The majority had hematologic diseases. All patients presented with sepsis in all 30 courses. Septic shock presented in 36.7% of these courses. The primary sites of infection included bloodstream infection (20.0%), skin and skin structure infection (20.0%), intra-abdominal infection (13.3%) and hospital-acquired pneumonia (10.0%). Twelve of the 25 (48.0%) patients had positive microbiological cultures, mainly Pseudomonas aeruginosa and Klebsiella pneumoniae, including 5 carbapenem-resistant GNB-infected cases. Fifteen (50.0%) courses presented clinical improvement. For the initial course of each patient, the clinical response rate of the GNB recovered group was significantly higher than that of the group without GNB recovery (66.7% vs 23.1%, P = 0.047). The 14-day and 30-day mortality rates were 24.0% and 28.0%, respectively, which were significantly correlated with the absence of GNB recovery (P = 0.004 and 0.024, respectively) and hospital-acquired pneumonia as the primary site of infection (P = 0.001 and 0.006, respectively). There was no significant difference in major outcomes between patients who received CAZ/AVI and matched patients who received other antibiotics. Conclusion: CAZ/AVI could be considered a salvage strategy for immunosuppressed children with confirmed GNB infection. Caution should be taken when CAZ/AVI is applied to these patients in the absence of GNB recovery.

Asunto(s)

Antibacterianos , Compuestos de Azabiciclo , Ceftazidima , Combinación de Medicamentos , Terapia Recuperativa , Humanos , Ceftazidima/administración & dosificación , Ceftazidima/uso terapéutico , Niño , Masculino , Femenino , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Compuestos de Azabiciclo/administración & dosificación , Compuestos de Azabiciclo/uso terapéutico , Preescolar , Huésped Inmunocomprometido , Adolescente , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Estudios Retrospectivos , Lactante , Pruebas de Sensibilidad Microbiana

RESUMEN

Despite advancements in antiretroviral therapy (ART) suppressing HIV-1 replication, existing antiviral drugs pose limitations, including lifelong medication, frequent administration, side effects and viral resistance, necessitating novel HIV-1 treatment approaches. CD4, pivotal for HIV-1 entry, poses challenges for drug development due to neutralization and cytotoxicity concerns. Nevertheless, Ibalizumab, the sole approved CD4-specific antibody for HIV-1 treatment, reignites interest in exploring alternative anti-HIV targets, emphasizing CD4's potential value for effective drug development. Here, we explore anti-CD4 nanobodies, particularly Nb457 from a CD4-immunized alpaca. Nb457 displays high potency and broad-spectrum activity against HIV-1, surpassing Ibalizumab's efficacy. Strikingly, engineered trimeric Nb457 nanobodies achieve complete inhibition against live HIV-1, outperforming Ibalizumab and parental Nb457. Structural analysis unveils Nb457-induced CD4 conformational changes impeding viral entry. Notably, Nb457 demonstrates therapeutic efficacy in humanized female mouse models. Our findings highlight anti-CD4 nanobodies as promising HIV-1 therapeutics, with potential implications for advancing clinical treatment against this global health challenge.

Asunto(s)

Antígenos CD4 , Camélidos del Nuevo Mundo , Anticuerpos Anti-VIH , Infecciones por VIH , VIH-1 , Anticuerpos de Dominio Único , VIH-1/inmunología , VIH-1/efectos de los fármacos , Anticuerpos de Dominio Único/farmacología , Anticuerpos de Dominio Único/inmunología , Animales , Antígenos CD4/inmunología , Antígenos CD4/metabolismo , Humanos , Infecciones por VIH/inmunología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Camélidos del Nuevo Mundo/inmunología , Anticuerpos Anti-VIH/inmunología , Anticuerpos Anti-VIH/farmacología , Ratones , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/farmacología , Conformación Proteica , Femenino , Internalización del Virus/efectos de los fármacos , Células HEK293 , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Anticuerpos Monoclonales

RESUMEN

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory disease in humans. High fatality rates and continued infectiousness remain a pressing concern for global health preparedness. Antibodies targeted at the receptor-binding domain (RBD) are major countermeasures against human viral infection. Here, we report four potent nanobodies against MERS-CoV, which are isolated from alpaca, and especially the potency of Nb14 is highest in the pseudotyped virus assay. Structural studies show that Nb14 framework regions (FRs) are mainly involved in interactions targeting a novel epitope, which is entirely distinct from all previously reported antibodies, and disrupt the protein-carbohydrate interaction between residue W535 of RBD and hDPP4 N229-linked carbohydrate moiety (hDPP4-N229-glycan). Different from Nb14, Nb9 targets the cryptic face of RBD, which is distinctive from the hDPP4 binding site and the Nb14 epitope, and it induces the ß5-ß6 loop to inflect towards a shallow groove of the RBD and dampens the accommodation of a short helix of hDPP4. The particularly striking epitopes endow the two Nbs administrate synergistically in the pseudotyped MERS-CoV assays. These results not only character unprecedented epitopes for antibody recognition but also provide promising agents for prophylaxis and therapy of MERS-CoV infection.

Asunto(s)

Anticuerpos Neutralizantes , Anticuerpos Antivirales , Infecciones por Coronavirus , Epítopos , Coronavirus del Síndrome Respiratorio de Oriente Medio , Anticuerpos de Dominio Único , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Anticuerpos de Dominio Único/inmunología , Anticuerpos de Dominio Único/química , Humanos , Epítopos/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Animales , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Camélidos del Nuevo Mundo/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/química , Ratones , Receptores Virales/metabolismo , Receptores Virales/inmunología

RESUMEN

Peptide-major histocompatibility complex (pMHC) multimers are wide recognized as the premier technique for detecting, characterizing, and isolating antigen-specific CD8+ T-cell subsets. These multimers are specifically useful in studying infections, autoimmune conditions, and cancer through single-cell analysis techniques such as flow cytometry and fluorescence microscopy. However, the development of high-throughput assays with commercially available pMHC tetramers can be expensive, while in-house production may pose challenges for most biology research laboratories. In this context, we introduce a cost-friendly and uncomplicated protocol to prepare empty MHC class I tetramers using disulfide-stabilized molecules and photolabile peptide ligands. Our method relies on disulfide bond-stabilized MHC-I molecules, which demonstrated stability when folded into stable monomers in the presence of a photolabile epitope. These monomers, upon ultraviolet irradiation and streptavidin binding, efficiently assemble into tetramers devoid of any peptide. Following a short incubation with the peptide of interest under gentle conditions, the resulting pMHC tetramer effectively detects patient-sourced, neoantigen-specific T cells. Our unique approach streamlines large-scale pMHC generation, thus paving the way for advancements in T cell-based diagnostics and personalized therapies.

Asunto(s)

Antígenos de Histocompatibilidad Clase I , Péptidos , Humanos , Péptidos/química , Péptidos/inmunología , Ligandos , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/química , Antígenos de Histocompatibilidad Clase I/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Multimerización de Proteína , Disulfuros/química , Rayos Ultravioleta

RESUMEN

Most of the state-of-the-art thermoelectric materials are inorganic semiconductors. Owing to the directional covalent bonding, they usually show limited plasticity at room temperature1,2, for example, with a tensile strain of less than five per cent. Here we discover that single-crystalline Mg3Bi2 shows a room-temperature tensile strain of up to 100 per cent when the tension is applied along the (0001) plane (that is, the ab plane). Such a value is at least one order of magnitude higher than that of traditional thermoelectric materials and outperforms many metals that crystallize in a similar structure. Experimentally, slip bands and dislocations are identified in the deformed Mg3Bi2, indicating the gliding of dislocations as the microscopic mechanism of plastic deformation. Analysis of chemical bonding reveals multiple planes with low slipping barrier energy, suggesting the existence of several slip systems in Mg3Bi2. In addition, continuous dynamic bonding during the slipping process prevents the cleavage of the atomic plane, thus sustaining a large plastic deformation. Importantly, the tellurium-doped single-crystalline Mg3Bi2 shows a power factor of about 55 microwatts per centimetre per kelvin squared and a figure of merit of about 0.65 at room temperature along the ab plane, which outperforms the existing ductile thermoelectric materials3,4.

RESUMEN

Research on the host responses to respiratory viruses could help develop effective interventions and therapies against the current and future pandemics from the host perspective. To explore the pathogenesis that distinguishes SARS-CoV-2 infections from other respiratory viruses, we performed a multi-cohort analysis with integrated bioinformatics and machine learning. We collected 3730 blood samples from both asymptomatic and symptomatic individuals infected with SARS-CoV-2, seasonal human coronavirus (sHCoVs), influenza virus (IFV), respiratory syncytial virus (RSV), or human rhinovirus (HRV) across 15 cohorts. First, we identified an enhanced cellular immune response but limited interferon activities in SARS-CoV-2 infection, especially in asymptomatic cases. Second, we identified a SARS-CoV-2-specific 3-gene signature (CLSPN, RBBP6, CCDC91) that was predominantly expressed by T cells, could distinguish SARS-CoV-2 infection, including Omicron, from other common respiratory viruses regardless of symptoms, and was predictive of SARS-CoV-2 infection before detectable viral RNA on RT-PCR testing in a longitude follow-up study. Thereafter, a user-friendly online tool, based on datasets collected here, was developed for querying a gene of interest across multiple viral infections. Our results not only identify a unique host response to the viral pathogenesis in SARS-CoV-2 but also provide insights into developing effective tools against viral pandemics from the host perspective.

Asunto(s)

COVID-19 , SARS-CoV-2 , Linfocitos T , Humanos , COVID-19/diagnóstico , COVID-19/virología , COVID-19/inmunología , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Linfocitos T/inmunología , Linfocitos T/virología , Estudios de Cohortes , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/diagnóstico , Biología Computacional/métodos , Adulto , Masculino , Persona de Mediana Edad , Femenino

RESUMEN

Pneumoconiosis is a common occupational disease that can worsen with accompanying infection. Torque teno virus (TTV) is a prevalent human virus with multiple genotypes that can chronically and persistently infect individuals. However, the prevalence of TTV in pneumoconiosis patients is still unclear. This research aims to detect the presence and prevalence of TTV in the alveolar lavage fluid of pneumoconiosis patients in the Hunan Province of China using PCR. As a result, a 65.5% positive rate (19 out of 29) of TTV was detected. The TTV detection rate varies among different stages of silicosis and different pneumoconiosis patient ages. Nine novel TTV genomes ranging in size from 3719 to 3908 nt, named TTV HNPP1, HNPP2, HNPP3, HNPP4, HNPP5, HNPP6-1, HNPP6-2, HNPP7-1 and HNPP7-2, were identified. A genomic comparison and phylogenetic analysis indicated that these nine TTVs represent five different species with high genetic diversity which belong to the genus Alphatorquevirus. HNPP6-1 and HNPP6-2 belong to TTV3, HNPP5 belongs to TTV13, HNPP1 belongs to TTV24, HNPP4 belongs to TTV20, and the others belong to TTV19. The genomes of TTV HNPP1, HNPP6-1, and HNPP6-2 contain three putative open reading frames (ORFs) coding for proteins, ORF1, ORF2, and ORF3, while the other six TTV genomes contain two ORFs coding for proteins, ORF1 and ORF2. These results provide the first description of TTV epidemiology in pneumoconiosis patients in China. The newly identified TTV genome sequences reveal the high genetic diversity of TTV in pneumoconiosis patients and could contribute to a deeper understanding of TTV retention and infection in humans.

Asunto(s)

Genoma Viral , Filogenia , Neumoconiosis , Torque teno virus , Humanos , Torque teno virus/genética , Torque teno virus/aislamiento & purificación , Torque teno virus/clasificación , China/epidemiología , Neumoconiosis/virología , Neumoconiosis/epidemiología , Neumoconiosis/genética , Masculino , Persona de Mediana Edad , Anciano , Infecciones por Virus ADN/virología , Infecciones por Virus ADN/epidemiología , Variación Genética , Genotipo , Adulto , Genómica/métodos , Femenino , Líquido del Lavado Bronquioalveolar/virología , ADN Viral/genética

RESUMEN

Wound management remains a challenge in clinical practice. Nowadays, patients have an increasing demand for wound repair with enhanced speed and quality; therefore, there is a great need to seek therapeutic strategies that can promote rapid and effective wound healing. In this study, we developed a carboxymethyl cellulose hydrogel loaded with l-carnosine (CRN@hydrogel) for potential application as a wound dressing. In vitro experiments confirmed that CRN@hydrogel can release over 80% of the drug within 48 h and demonstrated its favorable cytocompatibility and blood compatibility, thus establishing its applicability for safe utilization in clinical practice. Using a rat model, we found that this hydrogel could promote and accelerate wound healing more effectively. These results indicate that the novel hydrogel can serve as an efficient therapeutic strategy for wound treatment.

RESUMEN

BACKGROUND: Singapore, like the rest of Asia, faces persistent challenges to mental health promotion, including stigma around unwellness and seeking treatment and a lack of trained mental health personnel. The COVID-19 pandemic, which created a surge in mental health care needs and simultaneously accelerated the adoption of digital health solutions, revealed a new opportunity to quickly scale innovative solutions in the region. OBJECTIVE: In June 2020, the Singaporean government launched mindline.sg, an anonymous digital mental health resource website that has grown to include >500 curated local mental health resources, a clinically validated self-assessment tool for depression and anxiety, an artificial intelligence (AI) chatbot from Wysa designed to deliver digital therapeutic exercises, and a tailored version of the website for working adults called mindline at work. The goal of the platform is to empower Singapore residents to take charge of their own mental health and to be able to offer basic support to those around them through the ease and convenience of a barrier-free digital solution. METHODS: Website use is measured through click-level data analytics captured via Google Analytics and custom application programming interfaces, which in turn drive a customized analytics infrastructure based on the open-source platforms Titanium Database and Metabase. Unique, nonbounced (users that do not immediately navigate away from the site), engaged, and return users are reported. RESULTS: In the 2 years following launch (July 1, 2020, through June 30, 2022), the website received >447,000 visitors (approximately 15% of the target population of 3 million), 62.02% (277,727/447,783) of whom explored the site or engaged with resources (referred to as nonbounced visitors); 10.54% (29,271/277,727) of those nonbounced visitors returned. The most popular features on the platform were the dialogue-based therapeutic exercises delivered by the chatbot and the self-assessment tool, which were used by 25.54% (67,626/264,758) and 11.69% (32,469/277,727) of nonbounced visitors. On mindline at work, the rates of nonbounced visitors who engaged extensively (ie, spent ≥40 seconds exploring resources) and who returned were 51.56% (22,474/43,588) and 13.43% (5,853/43,588) over a year, respectively, compared to 30.9% (42,829/138,626) and 9.97% (13,822/138,626), respectively, on the generic mindline.sg site in the same year. CONCLUSIONS: The site has achieved desired reach and has seen a strong growth rate in the number of visitors, which required substantial and sustained digital marketing campaigns and strategic outreach partnerships. The site was careful to preserve anonymity, limiting the detail of analytics. The good levels of overall adoption encourage us to believe that mild to moderate mental health conditions and the social factors that underly them are amenable to digital interventions. While mindline.sg was primarily used in Singapore, we believe that similar solutions with local customization are widely and globally applicable.

Asunto(s)

COVID-19 , Salud Mental , Autocuidado , Humanos , Singapur , Autocuidado/métodos , Telemedicina , Promoción de la Salud/métodos , Internet , Pandemias , Inteligencia Artificial , SARS-CoV-2 , Servicios de Salud Mental

RESUMEN

Dynamic protein structures are crucial for deciphering their diverse biological functions. Two-dimensional infrared (2DIR) spectroscopy stands as an ideal tool for tracing rapid conformational evolutions in proteins. However, linking spectral characteristics to dynamic structures poses a formidable challenge. Here, we present a pretrained machine learning model based on 2DIR spectra analysis. This model has learned signal features from approximately 204,300 spectra to establish a "spectrum-structure" correlation, thereby tracing the dynamic conformations of proteins. It excels in accurately predicting the dynamic content changes of various secondary structures and demonstrates universal transferability on real folding trajectories spanning timescales from microseconds to milliseconds. Beyond exceptional predictive performance, the model offers attention-based spectral explanations of dynamic conformational changes. Our 2DIR-based pretrained model is anticipated to provide unique insights into the dynamic structural information of proteins in their native environments.

Asunto(s)

Aprendizaje Automático , Proteínas , Espectrofotometría Infrarroja , Proteínas/química , Espectrofotometría Infrarroja/métodos , Conformación Proteica , Pliegue de Proteína , Estructura Secundaria de Proteína

RESUMEN

Dengue fever is a viral illness, mainly transmitted by Aedes aegypti and Aedes albopictus. With climate change and urbanisation, more urbanised areas are becoming suitable for the survival and reproduction of dengue vector, consequently are becoming suitable for dengue transmission in China. Chongqing, a metropolis in southwestern China, has recently been hit by imported and local dengue fever, experiencing its first local outbreak in 2019. However, the genetic evolution dynamics of dengue viruses and the spatiotemporal patterns of imported and local dengue cases have not yet been elucidated. Hence, this study implemented phylogenetic analyses using genomic data of dengue viruses in 2019 and 2023 and a spatiotemporal analysis of dengue cases collected from 2013 to 2022. We sequenced a total of 15 nucleotide sequences of E genes. The dengue viruses formed separate clusters and were genetically related to those from Guangdong Province, China, and countries in Southeast Asia, including Laos, Thailand, Myanmar and Cambodia. Chongqing experienced a dengue outbreak in 2019 when 168 imported and 1,243 local cases were reported, mainly in September and October. Few cases were reported in 2013-2018, and only six were imported from 2020 to 2022 due to the COVID-19 lockdowns. Our findings suggest that dengue prevention in Chongqing should focus on domestic and overseas population mobility, especially in the Yubei and Wanzhou districts, where airports and railway stations are located, and the period between August and October when dengue outbreaks occur in endemic regions. Moreover, continuous vector monitoring should be implemented, especially during August-October, which would be useful for controlling the Aedes mosquitoes. This study is significant for defining Chongqing's appropriate dengue prevention and control strategies.

Asunto(s)

Virus del Dengue , Dengue , Filogenia , Análisis Espacio-Temporal , Dengue/epidemiología , Dengue/transmisión , Dengue/virología , China/epidemiología , Virus del Dengue/genética , Virus del Dengue/clasificación , Humanos , Brotes de Enfermedades , Animales , Aedes/virología , Enfermedades Transmisibles Importadas/epidemiología , Enfermedades Transmisibles Importadas/virología , Enfermedades Transmisibles Importadas/transmisión , Mosquitos Vectores/virología , Ciudades/epidemiología

RESUMEN

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

RESUMEN

Background: AAA is a fatal condition that commonly occurs during vascular surgery. Nutritional status exerts a significant influence on the prognosis of various pathological conditions Scores from the CONUT screening tool have been shown to predict outcomes of certain malignancies and chronic diseases. However, the ramifications of nutritional status on AAA patients undergoing EVAR have not been elucidated in prior studies. In this study, we aimed to elucidate the correlation between CONUT scores and postoperative prognostic outcomes in patients with AAA undergoing EVAR. Methods: This was a retrospective review of 177 AAA patients treated with EVAR from June 2018 to November 2019 in a single center. Patient characteristics, CONUT scores, and postoperative status were collected. These patients were stratified into groups A and B according to CONUT scores. Subsequently, a comparative analysis of the baseline characteristics between the two cohorts was conducted. Cox proportional hazards and logistic regression analyses were employed to identify the autonomous predictors of mid-term mortality and complications, respectively. Results: Compared with group A, patients in group B had higher midterm mortality (p < 0.001). Univariate analysis showed that CONUT scores; respiratory diseases; stent types; preoperative Hb, CRP, PT, and Fb levels were risk factors for death. Multivariate analysis confirmed that CONUT score [HR, 1.276; 95% CI, 1.029-1.584; p = 0.027] was an independent risk factor for mortality. Logistic regression analysis showed that prior arterial disease, smoking, and D-dimer levels were risk factors, although multivariate analysis showed smoking (OR, 3.492; 95% CI, 1.426-8.553; p = 0.006) was an independent risk factor. Kaplan-Meier curves showed that patients in group B had shorter mid-term survival than those in group A (log-rank p < 0.001). Conclusion: Malnutrition was strongly associated with mid-term mortality in patients with infrarenal AAA treated with EVAR.

RESUMEN

Introduction: Preeclampsia (PE) is a fundamental cause of preterm labor, intrauterine growth restriction, and persistent postpartum hypertension. In the present study, we aimed to investigate the correlation between 24-h urinary protein excretion, serum markers, and placental growth factor and their adverse pregnancy outcomes in patients with PE. Methods: A total of 126 pregnant women with PE (86 cases of mild PE and 40 cases of severe PE, assigned to the observation group) who came to our hospital from March 2019 to December 2021 for regular obstetric checkups and delivery were selected, with 60 healthy pregnant women assigned to the control group. Routine biochemical parameters, 24-h urinary protein quantification, serum parameters, and placental growth factor levels were recorded. The incidence of adverse neonatal pregnancy outcomes and abnormal fetal heart monitoring, neonatal body mass, 1 min Apgar score, and other adverse pregnancy outcomes were also analyzed in the different groups. Results: In comparison with healthy pregnant subjects, PE patients had earlier delivery gestational weeks (P < .05), significantly higher systolic blood pressure (SBP), diastolic blood pressure (DBP), 24-h urinary protein excretion, total cholesterol (TC), triglyceride (TG), D-Dimer and human chorionic gonadotropin (ß-hCG) levels (P < .05), lower albumin (ALB), platelet count, pregnant associated plasma protein A (PAPP-A) and placental growth factor (PLGF) (P < .05), and higher incidence of maternal and perinatal adverse outcomes (P < .05). Conclusions: Combined screening of 24-h urinary protein, PAPP-A, ß-hCG, PLGF, and serum indicators in early pregnancy are essential in predicting PE, allowing timely assessment of the risk of adverse pregnancy, and providing a basis for clinical intervention.