Dynamic encoding of temperature in the central circadian circuit coordinates physiological activities.

The circadian clock regulates animal physiological activities. How temperature reorganizes circadian-dependent physiological activities remains elusive. Here, using in-vivo two-photon imaging with the temperature control device, we investigated the response of the Drosophila central circadian circuit to temperature variation and identified that DN1as serves as the most sensitive temperature-sensing neurons. The circadian clock gate DN1a's diurnal temperature response. Trans-synaptic tracing, connectome analysis, and functional imaging data reveal that DN1as bidirectionally targets two circadian neuronal subsets: activity-related E cells and sleep-promoting DN3s. Specifically, behavioral data demonstrate that the DN1a-E cell circuit modulates the evening locomotion peak in response to cold temperature, while the DN1a-DN3 circuit controls the warm temperature-induced nocturnal sleep reduction. Our findings systematically and comprehensively illustrate how the central circadian circuit dynamically integrates temperature and light signals to effectively coordinate wakefulness and sleep at different times of the day, shedding light on the conserved neural mechanisms underlying temperature-regulated circadian physiology in animals.

Learning Stiffness Tensors in Self-Activated Solids via a Local Rule.

Mechanical metamaterials are often designed with particular properties for specific load-bearing functions. Alternatively, this study aims to create a class of active lattice metamaterials, dubbed self-activated solids, that can learn desired stiffness tensors from the elastic deformations they experienced, a crucial feature to improve the performance, efficiency, and functionality of materials. Artificial adaptive matters that combine sensory, control, and actuation elements can offer appealing solutions. However, challenges still remain: The designs will rely on accurate off-line and global computations, as well as intricate coordination among individual elements. Here, a simple online and local learning strategy is initiated based on contrastive Hebbian learning to gradually guide self-activated solids to possess sought-after stiffness tensors autonomously and reversibly. During learning, the bond stiffness of the active lattice varies depending only on its local strain. The numerical tests show that the self-activated solid can not only achieve the desired bulk, shear, and coupling moduli but also manifest uni-mode and bi-mode extremal materials by itself after experiencing the corresponding elastic deformations. Further, the self-activated solid can also achieve the desired time-varying moduli when exposed to temporally different loads. The design is applicable to any lattice geometries and is resistant to damage and instabilities. The material design approach and the physical learning strategy suggested can benefit the design of autonomous materials, physical learning machines, and adaptive robots.

Deep learning on tertiary lymphoid structures in hematoxylin-eosin predicts cancer prognosis and immunotherapy response.

Tertiary lymphoid structures (TLSs) have been associated with favorable immunotherapy responses and prognosis in various cancers. Despite their significance, their quantification using multiplex immunohistochemistry (mIHC) staining of T and B lymphocytes remains labor-intensive, limiting its clinical utility. To address this challenge, we curated a dataset from matched mIHC and H&E whole-slide images (WSIs) and developed a deep learning model for automated segmentation of TLSs. The model achieved Dice coefficients of 0.91 on the internal test set and 0.866 on the external validation set, along with intersection over union (IoU) scores of 0.819 and 0.787, respectively. The TLS ratio, defined as the segmented TLS area over the total tissue area, correlated with B lymphocyte levels and the expression of CXCL13, a chemokine associated with TLS formation, in 6140 patients spanning 16 tumor types from The Cancer Genome Atlas (TCGA). The prognostic models for overall survival indicated that the inclusion of the TLS ratio with TNM staging significantly enhanced the models' discriminative ability, outperforming the traditional models that solely incorporated TNM staging, in 10 out of 15 TCGA tumor types. Furthermore, when applied to biopsied treatment-naïve tumor samples, higher TLS ratios predicted a positive immunotherapy response across multiple cohorts, including specific therapies for esophageal squamous cell carcinoma, non-small cell lung cancer, and stomach adenocarcinoma. In conclusion, our deep learning-based approach offers an automated and reproducible method for TLS segmentation and quantification, highlighting its potential in predicting immunotherapy response and informing cancer prognosis.

Serum Uric Acid Levels among Chinese Children: Reference Values and Association With Overweight/Obesity.

This study aimed to investigate the reference values for serum uric acid (SUA) levels and their association with overweight/obese in children. We conducted a retrospective analysis of 8522 participants, including 6227 normal weight children, aged 2 to 18 years in China. Among normal children, SUA levels increased with age, showing significant sex differences in children over 10 years. Age-specific and sex-specific 95% reference intervals for SUA levels were established. Furthermore, we observed that the percentage of overweight/obesity significantly increased as SUA quartiles rose. Elevated SUA levels were associated with a high odds ratio (OR) for overweight/obesity (OR = 4.45, 95% confidence interval = 3.33, 5.93). We propose that the 97.5th percentile is a suitable value for defining elevated SUA levels, and there is a positive correlation between SUA levels and the presence of overweight or obesity.

In-situ sparse-array imaging for through-thickness cracks in plates with A0 Lamb waves and an efficient waveform inversion algorithm.

Structural health monitoring (SHM) requires efficient online crack detection and characterization to prevent structural failures, which mainly arise from fatigue cracks. Existing solutions for crack characterization involve analyzing sensed wave signals directly, but these approaches usually require onerous steps or many sensors to obtain sufficient and clear wave packets. An alternative strategy is a model-based inversion, which takes the full waveform into consideration and does not require analysis on a single wave packet. This approach can achieve accurate characterization with fewer sensors and simpler implementation. We propose an efficient model based on the Huygens' principle and the no-mode-conversion property of the A0 mode Lamb waves to meet the requirements of online monitoring. We then verify the proposed model-based crack imaging method through simulation and experiments on smooth and rough cracks. The proposed method is easy, cheap, and efficient, making it a desirable option for SHM tasks.

Histone Variant H3.3 Controls Arabidopsis Fertility by Regulating Male Gamete Development.

Reprograming of chromatin structures and changes in gene expression are critical for plant male gamete development, and epigenetic marks play an important role in these processes. Histone variant H3.3 is abundant in euchromatin and is largely associated with transcriptional activation. The precise function of H3.3 in gamete development remains unclear in plants. Here, we report that H3.3 is abundantly expressed in Arabidopsis anthers and its knockout mutant h3.3-1 is sterile due to male sterility. Transcriptome analysis of young inflorescence has identified 2348 genes downregulated in h3.3-1 mutant, among which 1087 target genes are directly bound by H3.3, especially at their 3' ends. As a group, this set of H3.3 targets is enriched in the reproduction-associated processes including male gamete generation, pollen sperm cell differentiation and pollen tube growth. The function of H3.3 in male gamete development is dependent on the Anti-Silencing Factor 1A/1B (ASF1A/1B)-Histone regulator A (HIRA)-mediated pathway. Our results suggest that ASF1A/1B-HIRA-mediated H3.3 deposition at its direct targets for transcription activation forms the regulatory networks responsible for male gamete development.

Obstructive sleep apnea promotes the progression of lung cancer by modulating cancer cell invasion and cancer-associated fibroblast activation via TGFß signaling.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with severity of pneumonia; however, the mechanism by which OSA promotes lung cancer progression is unclear. METHODS: Twenty-five lung cancer patients were recruited to investigate the relationship between OSA and cancer-associated fibroblast (CAFs) activation. Lung cancer cells (A549) and WI38 fibroblast cells were used to explore the hypoxia-induced TGFß expression using qPCR, Western blot, and ELISA. Wound healing and transwell assays were performed to evaluate cancer cell migration and invasion. A549 or A549-Luc + WI38 xenograft mouse models were established to detect the intermittent hypoxia (IH) associated with lung tumor growth and epithelial-mesenchymal transition (EMT) in vivo. RESULTS: OSA promotes CAF activation and enrichment in lung cancer patients. Hypoxia (OSA-like treatment) activated TGFß signaling in both lung cancer cells and fibroblasts, which promoted cancer cell migration and invasion, and enriched CAFs. IH promoted the progression and EMT process of lung cancer xenograft tumor. Co-inoculation of lung cancer cells and fibroblast cells could further promote lung cancer progression. CONCLUSIONS: IH promotes lung cancer progression by upregulating TGFß signaling, promoting lung cancer cell migration, and increasing the CAF activation and proportion of lung tumors.

Leydig cell metabolic disorder act as a new mechanism affecting for focal spermatogenesis in Klinefelter syndrome patients: a real world cross-sectional study base on the age.

Background: Klinefelter's syndrome (KS) was once considered infertile due to congenital chromosomal abnormalities, but the presence of focal spermatozoa changed this. The key to predict and promote spermatogenesis is to find targets that regulate focal spermatogenesis. Objective: To explore the trend of fertility changes in KS patients at different ages and identify potential therapeutic targets. Methods: Bibliometric analysis was used to collect clinical research data on KS from the Web of Science Core Collection (WoSCC) from 1992 to 2022. A cross-sectional study was conducted on 75 KS patients who underwent microscopic testicular sperm extraction (mTESE) from 2017 to 2022 in the real world. The reproductive hormones, testicular histopathology, androgen receptors, insulin-like factor 3 (INSL3) receptors and sperm recovery rate (SRR) were analyzed. Results: Male infertility, dysplasia, Sertoli cells, Leydig cells, testosterone and spermatogenesis were the research focuses related to KS. Luteinizing hormone (LH), testosterone, and INSL3 were evaluation indicators of Leydig cell function that fluctuate with age. Testosterone and LH peaked at ages 13-19 and 30-45, while INSL3 only peaked at ages 13-19. 27 patients (27/75) recovered sperm through mTESE and experienced SRR peaks at the ages of 20, 28, 34, and 37. The SRR of fibrosis patients was 46.15%, fatty degeneration was 7.14%, and melanosis was 40.00%. The INSL3 and androgen receptors were highly expressed and roughly balanced in focal spermatogenesis. Conclusion: Abnormal metabolism of Leydig cells led to imbalanced expression of INSL3 and androgen receptors, which might be a potential target for spermatogenesis in KS.

Diversities of disability caused by lung cancer in the 66 Belt and Road initiative countries: a secondary analysis from the Global Burden of Disease Study 2019.

Objectives: Due to the increase in life expectancy and the aging of the global population, the "Belt and Road" ("B&R") countries are faced with varying degrees of lung cancer threat. The purpose of this study is to analyze the differences in the burden and trend of lung cancer disability in the "B&R" countries from 1990 to 2019 so as to provide an analytical strategic basis to build a healthy "B&R". Methods: Data were derived from the Global Burden of Disease 2019 (GBD 2019). Incidence, mortality, prevalence, the years lived with disability (YLDs), and disability-adjusted life years (DALYs) of lung cancer and those attributable to different risk factors were measured from 1990 to 2019. Trends of disease burden were estimated by using the average annual percent change (AAPC), and the 95% uncertainty interval (UI) was reported. Results: China, India, and the Russian Federation were the three countries with the highest burden of lung cancer in 2019. From 1990 to 2019, the AAPC of incidence, prevalence, mortality, and DALYs generally showed a downward trend in Central Asia (except Georgia) and Eastern Europe, while in China, South Asia (except Bangladesh), most countries in North Africa, and the Middle East, the trend was mainly upward. The AAPC of age-standardized incidence was 1.33% (1.15%-1.50%); the AAPC of prevalence, mortality, and DALYs from lung cancer in China increased by 24% (2.10%-2.38%), 0.94% (0.74%-1.14%), and 0.42% (0.25%-0.59%), respectively. A downward trend of the AAPC values of age-standardized YLD rate in men was shown in the vast majority of "B&R" countries, but for women, most countries had an upward trend. For adults aged 75 years or older, the age-standardized YLD rate showed an increasing trend in most of the "B&R" countries. Except for the DALY rate of lung cancer attributable to metabolic risks, a downward trend of the DALY rate attributable to all risk factors, behavioral risks, and environmental/occupational risks was shown in the vast majority of "B&R" countries. Conclusion: The burden of lung cancer in "B&R" countries varied significantly between regions, genders, and risk factors. Strengthening health cooperation among the "B&R" countries will help to jointly build a community with a shared future for mankind.

A Common Functional Variant at the Enhancer of the Rheumatoid Arthritis Risk Gene ORMDL3 Regulates its Expression Through Allele-Specific JunD Binding.

Genome-wide association studies (GWASs) have identified over 100 loci associated with rheumatoid arthritis (RA); however, the functionally affected genes and the underlying molecular mechanisms contributing to these associations are often unknown. In this study, we conducted an integrative genomic analysis incorporating multiple "omics" data and identified a functional regulatory DNA variant, rs56199421, and a plausible mechanism by which it regulates the expression of a putative RA risk gene, ORMDL Sphingolipid Biosynthesis Regulator 3 (ORMDL3). The T allele of rs56199421, located in the enhancer region of ORMDL3, exhibited stronger direct binding ability than the other C allele of rs56199421 did in vitro with the transcription factor JunD and demonstrated higher transcriptional activity. Moreover, the T allele of rs56199421 is associated with elevated RA risk, and ORMDL3 expression is increased in RA patients. Thus, these findings suggest that the T allele of rs56199421 enhances JunD transcription factor binding, increases enhancer activity, and elevates the expression of the RA risk gene ORMDL3. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00107-z.

BNIP3 as a potential biomarker for the identification of prognosis and diagnosis in solid tumours.

BACKGROUND: Traditional radiotherapy and chemotherapy have been intensively studied for their role in the treatment of tumours. However, these therapies often cause side effects for patients, which calls for the development of novel treatment options for tumours. B-cell lymphoma-2 (Bcl-2)/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) reportedly apoptosis-inducing effects in tumour cells and is associated with the progression and treatment of multiple tumours. Nevertheless, little is known about its potential role in tumour diagnosis and targeted therapy. FINDINGS: The results of the study demonstrated that the interaction of BNIP3 with HDAC1 may affect the progression of breast invasive cancer (BRCA), sarcoma (SARC), kidney renal clear cell carcinoma (KIRC), and low-grade glioma (LGG). BNIP3 seemed to exert its effects in BRCA and SARC primarily through gene silencing and integrator complex, and in KIRC and LGG, mainly by affecting olfactory function, suggesting that targeted therapy can be developed based on the above signalling pathway and downstream molecules. INTERPRETATION: BNIP3 has emerged as a promising therapeutic and diagnostic target for BRCA, SARC, KIRC, and LGG, providing new insights into tumour molecular therapies in the clinic.

Blockade of IL-11 Trans-Signaling or JAK2/STAT3 Signaling Ameliorates the Profibrotic Effect of IL-11.

OBJECTIVES: Systemic sclerosis (SSc) is a rare rheumatic disease characterized by vascular damage, dysregulated immune response, and fibrosis. Interleukin-11 (IL-11) is upregulated in SSc. This study aimed to investigate the pathological and therapeutic role of the IL-11 trans-signaling pathway in SSc. METHODS: Plasma IL-11 level was evaluated in 32 patients with SSc and 15 healthy controls, while the expression levels of ADAM10, ADAM17, IL-11, IL-11 Rα, or IL-11 co-stained with CD3 or CD163 in the skin of SSc patients and healthy controls were analyzed. Fibroblasts were treated with IL-11 and ionomycin to evaluate the profibrotic effect of IL-11 trans-signaling pathway. TJ301 (sgp130Fc) and WP1066 (a JAK2/STAT3 inhibitor) intervention groups were set up to investigate the antifibrotic effect of targeting IL-11. RESULTS: Levels of plasma IL-11 were extremely low in most SSc patients and healthy controls. In contrast, levels of IL-11, IL-11 Rα, and ADAM10, but not ADAM17, were significantly elevated in the skin of SSc patients. Moreover, the numbers of IL-11+ CD3+ cells and IL-11+ CD163+ cells were increased in the skin of SSc patients. Besides, IL-11 and ADAM10 were also elevated in the skin and pulmonary of bleomycin-induced SSc mouse. Fibroblasts co-stimulated with IL-11 and ionomycin showed increased expression of COL3 and phosphorylation of STAT3, which could be inhibited by TJ301 or WP1066. TJ301 also ameliorated skin and lung fibrosis in BLM-induced SSc mouse. CONCLUSIONS: IL-11 induces fibrosis in SSc by regulating the trans-signaling pathway. Blockage of sgp130Fc or inhibition of the JAK2/STAT3 pathway could ameliorate the profibrotic effect of IL-11.

Intermittent hypoxia inhibits anti-tumor immune response via regulating PD-L1 expression in lung cancer cells and tumor-associated macrophages.

Accumulating evidence has shown an increased tumor incidence and reduced survival rate in cancer patients with obstructive sleep apnea (OSA). Although intermittent hypoxia is known to play a crucial role, the molecular mechanism by which intermittent hypoxia accelerates lung cancer progression remains to be elucidated.A lung cancer xenograft mouse model was established by subcutaneously injecting LLC cells into C57BL/6 mice. The tumor-bearing mice were exposed to either normoxia or intermittent hypoxia and received either IgG2a, anti-programmed death ligand-1 (PD-L1), PX-478, or anti-PD-L1 + PX-478 treatment.A significant upregulation of tumor associated macrophages (TAMs) papulation and PD-L1 levels was observed in lung adenocarcinoma patients with OSA. We further confirmed that hypoxia-inducible factor-1 alpha (HIF-1α) regulates PD-L1 at transcriptional levels, mainly through binding to the hypoxia response element 4. Using a lung cancer xenograft mouse model, we observed that intermittent hypoxia exposed tumors grew faster and bigger with upregulated HIF-1α and PD-L1 expression, enhanced TAMs and Treg populations, and reduced cytotoxic T cells and cytokine secretion. Finally, we found a combination of PX-478 and anti-PD-L1 exerted an encouraging tumor inhibition effect compared to single treatment. Combination therapies based on HIF-1α and PD-L1 blockade might serve as a promising strategy to treat lung cancer patients with OSA.

Efficacy and Safety of Meal Replacement in Patients With Type 2 Diabetes.

CONTEXT: Meal replacement (MR) is beneficial for the management of type 2 diabetes (T2D). However, MR prescription and patient characteristics vary substantially between studies using MR in T2D patients. OBJECTIVE: This work aimed to evaluate the efficacy and safety of MR in T2D patients by meta-analysis, with a focus on subgroup analysis of variable participant characteristics and MR prescription. METHODS: We searched PubMed, CENTRAL, Embase, Web of Science, and the clinical trial registration database up to March 2022. We included randomized controlled trials (RCTs) of 2 weeks or more assessing the effect and safety of MR in T2D patients in comparison with conventional diabetic diets (CDs). RESULTS: A total of 17 RCTs involving 2112 participants were ultimately included. Compared with CDs, MR significantly reduced glycated hemoglobin A1c (HbA1c) (MD -0.46%; P < .001), fasting blood glucose (FBG, -0.62 mmol/L; P < .001), body weight (-2.43 kg; P < .001), and body mass index (BMI, -0.65; P < .001), and improved other cardiometabolic risk factors. In subgroup analyses, total MR showed greater improvement in HbA1c (-0.72% vs -0.32%; P = .01), FBG (-1.45 vs -0.56 mmol/L; P = .02), body weight (-6.57 vs -1.58 kg; P < .001), and BMI (-2.78 vs -0.37; P < .001) than partial MR. MR with caloric restriction showed more reduction in body weight (-3.20 vs -0.75 kg; P < .001) and BMI (-0.84 vs -0.24; P = .003) compared with those without caloric restriction. MR showed similar benefits in studies that included patients using insulin and those that did not. Both partial and total MR were well tolerated. CONCLUSION: Compared with CDs, the MR-based dietary pattern further improved the glycemic control and adipose indicators in T2D patients. Appropriate calorie restriction and total MR might be more beneficial, while both patients treated with or without insulin treatment could similarly benefit from MR usage.

Paternal age, risk of congenital anomalies, and birth outcomes: a population-based cohort study.

The objective of the study was to explore the impact of paternal age on the risk of congenital anomalies and birth outcomes in infants born in the USA between 2016 and 2021. This retrospective cohort study used data from the National Vital Statistics System (NVSS) database, a data set containing information on live birth in the USA between 2016 and 2021. Newborns were divided into four groups based on their paternal age (< 25, 25-34, 35-44, and > 44 years) and using the 25-34 age group as a reference. The primary outcomes were congenital anomalies involving structural anomalies and chromosome anomalies. Secondary outcomes were preterm birth, low birth weight, severe neonatal perinatal asphyxia, and admission to neonatal intensive care units (NICU). A multivariable logistic regression model was used to analyze the association between paternal age and outcomes. Overall, 17,764,695 live births were included in the final analyses. After adjusting confounding factors, advanced paternal age > 44 years was associated with increased odds of congenital anomalies (adjusted odds ratio (aOR) = 1.17, 95%CI 1.12-1.21) compared with the 25-34 age group, mainly for the chromosomal anomalies (aOR = 1.59, 95%CI 1.40-1.78) but not the structure anomalies (aOR = 1.03, 95%CI 0.97-1.09). The risk of preterm delivery, low birth weight, and NICU hospitalization in their infants was increased by advanced parental age as well.  Conclusion: Advanced paternal age increases the risk of congenital anomalies, especially chromosomal anomalies in their offspring, implying prenatal genetic counseling is required. What is Known: • There's a rising trend of advanced paternal age, which is associated with an increased likelihood of premature birth and low birth weight in their offspring. However, the exploration between paternal age and congenital abnormalities in offspring was limited and contradictory. What is New: • Infants with a paternal age > 44 years were more likely to be born with congenital anomalies, especially chromosomal anomalies.

The dynamics of H2A.Z on SMALL AUXIN UP RNAs regulate abscisic acid-auxin signaling crosstalk in Arabidopsis.

Extreme environmental changes threaten plant survival and worldwide food production. In response to osmotic stress, the plant hormone abscisic acid (ABA) activates stress responses and restricts plant growth. However, the epigenetic regulation of ABA signaling and crosstalk between ABA and auxin are not well known. Here, we report that the histone variant H2A.Z-knockdown mutant in Arabidopsis Col-0, h2a.z-kd, has altered ABA signaling and stress responses. RNA-sequencing data showed that a majority of stress-related genes are activated in h2a.z-kd. In addition, we found that ABA directly promotes the deposition of H2A.Z on SMALL AUXIN UP RNAs (SAURs), and that this is involved in ABA-repression of SAUR expression. Moreover, we found that ABA represses the transcription of H2A.Z genes through suppressing the ARF7/19-HB22/25 module. Our results shed light on a dynamic and reciprocal regulation hub through H2A.Z deposition on SAURs and ARF7/19-HB22/25-mediated H2A.Z transcription to integrate ABA/auxin signaling and regulate stress responses in Arabidopsis.

Baicalein-corrected gut microbiota may underlie the amelioration of memory and cognitive deficits in APP/PS1 mice.

Background: Baicalein is an active ingredient extracted from the root of S. baicalensis Georgi, which exhibits cardiovascular protection, anti-inflammatory, and anti-microbial properties. Our previous study showed that chronic treatment of Baicalein ameliorated cognitive dysfunction in a mouse model of Alzheimer's disease (AD). However, it remains unknown whether Baicalein ameliorates cognitive deficits in AD mouse models by altering gut microbiota and its metabolites. Methods: Behavioral tests, metagenomic and untargeted metabolomics analyses were used to evaluate the effects of Baicalein on the APP/PS1 mice. Results: Our research showed that treatment of Baicalein for 2 weeks ameliorated cognition and memory in a dose-dependent manner, as indicated by the significant increases in the Discrimination index and Number of crossings and decrease in latency to the previous platform location in 8-month of age APP/PS1 mice in novel object recognition and water maze tests. The metagenomic analysis showed the abundance of the dominant phyla in all groups, including Bacteroidetes (14.59%-67.02%) and Firmicutes (20.19%-61.39%). LEfSe analysis of metagenomics identified three species such as s__Roseburia_sp_1XD42_69, s__Muribaculaceae_bacterium_Isolate_104_HZI, s__Muribaculaceae_bacterium_Isolate_110_HZI as Baicalein-treated potential biomarkers. Metabolite analysis revealed the increment of metabolites, including glutamate, thymine and hexanoyl-CoA. Conclusion: The effects of Baicalein on memory and cognition may relate to the metabolism of nucleotides, lipids and glucose.

Impact of public health and social measures on contact dynamics during a SARS-CoV-2 Omicron variant outbreak in Quanzhou, China, March to April 2022.

OBJECTIVES: To evaluate the impact of early implementation of public health and social measures (PHSMs) on contact rates over time and explore contact behavior of asymptomatic versus symptomatic cases. METHODS: We used the largest contact tracing data in China thus far to estimate the mean contacts over time by age groups and contact settings. We used bootstrap with replacement to quantify the uncertainty of contact matrixes. The Pearson correlation was performed to demonstrate the number of contacts over time in relation to the evolution of restrictions. In addition, we analyzed the index cases with a high number of contacts and index cases that produced a high number of secondary cases. RESULTS: Rapidly adapted PHSMs can reduce the mean contact rates in public places while increasing the mean contact rates within households. The mean contact rates were 11.81 (95% confidence interval, 11.61-12.01) for asymptomatic (at the time of investigation) cases and 6.70 (95% confidence interval, 6.54-6.87) for symptomatic cases. The percentage of asymptomatic cases (at the time of investigation) meeting >50 close contacts make up more than 65% of the overall cases. The percentage of asymptomatic cases producing >10 secondary cases account for more than 80% of the overall cases. CONCLUSION: PHSMs may increase the contacts within the household, necessitating the need for pertinent prevention strategies at home. Asymptomatic cases can contribute significantly to Omicron transmission. By making asymptomatic people aware that they are already contagious, hence limiting their social contacts, it is possible to lower the transmission risk.

Oxygenation index and NT-proBNP as predictors of pulmonary hypertension and ventilation/perfusion mismatch in acute pulmonary embolism.

Introduction: The magnitude of pulmonary artery pressure (PAP) and the extent of ventilation/perfusion (V/Q) mismatch are essential for assessing the prognosis of acute pulmonary embolism (APE). We aimed to develop a model for predicting the status of the pulmonary circulation and arterial gas exchange functions using serum levels of cardiac biomarkers and arterial oxygenation index (OI) values. Materials and methods: This single-center, retrospective observational cohort study included 224 patients with APE. Multivariate linear regression and Poisson regression were used to test the statistical association between cardiac biomarkers, OI, PAP, and V/Q mismatch. Diagnostic efficiency was calculated from a receiver operating characteristic (ROC) curve. Results: Serum levels of troponin I (TNI), N-terminal pro-brain natriuretic peptide (NT-proBNP), and arterial OI magnitude significantly correlated with PAP and V/Q mismatches (P < 0.05). Multivariate linear regression showed that NT-proBNP serum levels (ß = 0.002, P < 0.001) and OI values (ß = -0.022, P = 0.001) significantly influenced PAP. Arterial OI (ß = -0.039, P < 0.001) had a significant influence on the percentage of pulmonary vascular obstruction (PVO) as determined by perfusion scanning. Poisson regression showed that OI (odds ratio: 0.995, p < 0.001) was a predictor of the number of lung segments with V/Q mismatches. ROC area under the curve (AUC) values of NT-proBNP and OI predicting pulmonary hypertension were 0.716 and 0.730, respectively, and for V/Q mismatch scanning, the results were 0.601 and 0.634, respectively. Conclusion: Arterial OI and serum levels of cardiac biomarkers may be used as indicators of pulmonary hypertension and V/Q mismatch.