IMP: bridging the gap for medicinal plant genomics.

Medicinal plants have garnered significant attention in ethnomedicine and traditional medicine due to their potential antitumor, anti-inflammatory and antioxidant properties. Recent advancements in genome sequencing and synthetic biology have revitalized interest in natural products. Despite the availability of sequenced genomes and transcriptomes of these plants, the absence of publicly accessible gene annotations and tabular formatted gene expression data has hindered their effective utilization. To address this pressing issue, we have developed IMP (Integrated Medicinal Plantomics), a freely accessible platform at https://www.bic.ac.cn/IMP. IMP curated a total of 8 565 672 genes for 84 high-quality genome assemblies, and 2156 transcriptome sequencing samples encompassing various organs, tissues, developmental stages and stimulations. With the integrated 10 analysis modules, users could simply examine gene annotations, sequences, functions, distributions and expressions in IMP in a one-stop mode. We firmly believe that IMP will play a vital role in enhancing the understanding of molecular metabolic pathways in medicinal plants or plants with medicinal benefits, thereby driving advancements in synthetic biology, and facilitating the exploration of natural sources for valuable chemical constituents like drug discovery and drug production.

Assessment of Humoral Immune Responses to Repeated Influenza Vaccination in a Multiyear Cohort: A 5-Year Follow-up.

The long-term effects of host factors on vaccine-elicited immune responses have not been well studied, and the interactions of host factors with annual influenza vaccinations are yet to be explored. We analyzed data from a cohort of 386 individuals who received the standard-dose influenza vaccine and enrolled in ≥2 seasons from 2016 to 2020. Our analyses indicated disparate vaccine-elicited immune responses between males and females in adults when they were repeatedly vaccinated for at least 2 seasons. Notably, we found interactive effects between age and body mass index (BMI) on overall immune responses, and between sex at birth and BMI in adults.

Trimester-Specific Urinary Strontium Concentrations during Pregnancy and Longitudinally Assessed Fetal Growth: Findings from a Prospective Cohort.

BACKGROUND: Studies have claimed that strontium (Sr) is associated with fetal growth, but the research evidence is insufficient. OBJECTIVES: Our study aimed to evaluate associations of trimester-specific urinary Sr concentrations with fetal growth parameters and birth size indicators. METHODS: In this prospective cohort, 9015 urine samples (first trimester: 3561, 2nd trimester: 2756, 3rd trimester: 2698) from 3810 mothers were measured for urinary Sr levels using inductively coupled plasma mass spectrometry (ICP-MS) and adjusted to urine specific gravity. We calculated standard deviation scores (SD-scores) for ultrasound-measured fetal growth parameters (head circumference, abdominal circumference, femur length, and estimated fetal weight) at 16, 24, 31, and 37 wk of gestation and birth size indicators (birth weight, birth length, and Ponderal index). Generalized linear models and generalized estimating equations models were used. Models were adjusted for potential covariates (gestational age, maternal age, body mass index, parity, passive smoking during pregnancy, education, folic acid supplements use, physical activity, maternal and paternal height, and infant sex). RESULTS: Positive associations of naturally logarithm-transformed Sr concentrations with fetal growth parameters and birth size indicators were observed. With each doubling increase in the urinary ln-Sr level in all 3 trimesters resulting in a percent change in SD-scores fetal growth parameters at 24, 31, and 37 wk of gestation and birth size indicators, 5.09%-8.23% in femur length, 7.57%-11.53% in estimated fetal weight, 6.56%-10.42% in abdominal circumference, 6.25% in head circumference, 5.15%-7.85% in birth weight, and 5.71%-9.39% in birth length, respectively. Most of the above statistical results could only be observed in male fetuses. CONCLUSIONS: Our findings suggest a potential association between Sr concentration and increased fetal growth, but these results and underlying mechanisms need further confirmation and clarification.

The role of the JAK/STAT3 signaling pathway in acquired corneal diseases.

Acquired corneal diseases such as dry eye disease (DED), keratitis and corneal alkali burns are significant contributors to vision impairment worldwide, and more effective and innovative therapies are urgently needed. The Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway plays an indispensable role in cell metabolism, inflammation and the immune response. Studies have shown that regulators of this pathway are extensively expressed in the cornea, inducing significant activation of JAK/STAT3 signaling in specific acquired corneal diseases. The activation of JAK/STAT3 signaling contributes to various pathophysiological processes in the cornea, including inflammation, neovascularization, fibrosis, and wound healing. In the context of DED, the hypertonic environment activates JAK/STAT3 signaling to stimulate corneal inflammation. Inflammation and injury progression in infectious keratitis can also be modulated by JAK/STAT3 signaling. Furthermore, JAK/STAT3 signaling is involved in every stage of corneal repair after alkali burns, including acute inflammation, angiogenesis and fibrosis. Treatments modulating JAK/STAT3 signaling have shown promising results in attenuating corneal damage, indicating its potential as a novel therapeutic target. Thus, this review emphasizes the multiple roles of the JAK/STAT3 signaling pathway in common acquired corneal disorders and summarizes the current achievements of JAK/STAT3-targeting therapy to provide new insights into future applications.

CircRNA expression profiles and regulatory networks in the vitreous humor of people with high myopia.

Myopia is a global health and economic issue. Circular RNAs (circRNAs) have been shown to play an important role in the pathogenesis of many ocular diseases. We first evaluated the circRNA profiles and possible roles in vitreous humor samples of individuals with high myopia by a competitive endogenous RNA (ceRNA) array. Vitreous humor samples were collected from 15 high myopic (5 for ceRNA array, and 10 for qPCR) and 15 control eyes (5 for ceRNA array, and 10 for qPCR) with idiopathic epiretinal membrane (ERM) and macular hole (MH). 486 circRNAs (339 upregulated and 147 downregulated) and 264 mRNAs (202 upregulated and 62 downregulated) were differentially expressed between the high myopia and control groups. The expression of hsa_circ_0033079 (hsa-circDicer1), hsa_circ_0029989 (hsa-circNbea), hsa_circ_0019072 (hsa-circPank1) and hsa_circ_0089716 (hsa-circEhmt1) were validated by qPCR. Pearson analysis and multivariate regression analysis showed positive and significant correlations for axial length with hsa-circNbea and hsa-circPank1. KEGG analysis showed that the target genes of circRNAs were enriched in the mTOR, insulin, cAMP, and VEGF signaling pathways. GO analysis indicated that circRNAs mainly targeted transcription, cytoplasm, and protein binding. CircRNA-associated ceRNA network analysis and PPI network analysis identified several critical genes for myopia. The expression of circNbea, circPank1, miR-145-5p, miR-204-5p, Nras, Itpr1 were validated by qPCR in the sclera of form-deprivation myopia (FDM) mice model. CircPank1/miR-145-5p/NRAS and circNbea/miR-204-5p/ITPR1 were identified and may be important in the progression of myopia. Our findings suggest that circRNAs may contribute to the pathogenesis of myopia and may serve as potential biomarkers.

Characterization of Retinal VIP-Amacrine Cell Development During the Critical Period.

Retinal vasoactive intestinal peptide amacrine cells (VIP-ACs) play an important role in various retinal light-mediated pathological processes related to different developmental ocular diseases and even mental disorders. It is important to characterize the developmental changes in VIP-ACs to further elucidate their mechanisms of circuit function. We bred VIP-Cre mice with Ai14 and Ai32 to specifically label retinal VIP-ACs. The VIP-AC soma and spine density generally increased, from postnatal day (P)0 to P35, reaching adult levels at P14 and P28, respectively. The VIP-AC soma density curve was different with the VIP-AC spine density curve. The total retinal VIP content reached a high level plateau at P14 but was decreased in adults. From P14 to P16, the resting membrane potential (RMP) became more negative, and the input resistance decreased. Cell membrane capacitance (MC) showed three peaks at P7, P12 and P16. The RMP and MC reached a stable level similar to the adult level at P18, whereas input resistance reached a stable level at P21. The percentage of sustained voltage-dependent potassium currents peaked at P16 and remained stable thereafter. The spontaneous excitatory postsynaptic current and spontaneous inhibitory postsynaptic current frequencies and amplitudes, as well as charge transfer, peaked at P12 to P16; however, there were also secondary peaks at different time points. In conclusion, we found that the second, third and fourth weeks after birth were important periods of VIP-AC development. Many developmental changes occurred around eye opening. The development of soma, dendrite and electrophysiological properties showed uneven dynamics of progression. Cell differentiation may contribute to soma development whereas the changes of different ion channels may play important role for spine development.

Uncovering the role of ferroptosis in Bietti crystalline dystrophy and potential therapeutic strategies.

PURPOSE: Bietti crystalline dystrophy (BCD) is an inherited retinal degeneration disease caused by mutations in the CYP4V2 gene. Currently, there is no clinical therapy approach available for BCD patients. Previous research has suggested that polyunsaturated fatty acids (PUFAs) may play a significant role in the development of BCD, implicating the involvement of ferroptosis in disease pathogenesis. In this work, we aimed to investigate the interplay between ferroptosis and BCD and to detect potential therapeutic strategies for the disease. METHODS: Genetic-edited RPE cell line was first established in this study by CRISPR-Cas9 technology. Cyp4v3 (the homologous gene of human CYP4V2) knock out (KO) mice have also been used. Lipid profiling and transcriptome analysis of retinal pigment epithelium (RPE) cells from Cyp4v3 KO mice have been conducted. Ferroptosis phenotypes have been first investigated in BCD models in vitro and in vivo, including lipid peroxidation, mitochondrial changes, elevated levels of reactive oxygen species (ROS), and altered gene expression. Additionally, an iron chelator, deferiprone (DFP), has been tested in vitro and in vivo to determine its efficacy in suppressing ferroptosis and restoring the BCD phenotype. RESULTS: Cyp4v3 KO mice exhibited progressive retinal degeneration and lipid accumulation, similar to the BCD phenotype, which was exacerbated by a high-fat diet (HFD). Increased levels of PUFAs, such as EPA (C22:5) and AA (C20:4), were observed in the RPE of Cyp4v3 KO mice. Transcriptome analysis of RPE in Cyp4v3 KO mice revealed changes in genes involved in iron homeostasis, particularly an upregulation of NCOA4, which was confirmed by immunofluorescence. Ferroptosis-related characteristics, including mitochondrial defects, lipid peroxidation, ROS accumulation, and upregulation of related genes, were detected in the RPE both in vitro and in vivo. Abnormal accumulation of ferrous iron was also detected. DFP, an iron chelator administration suppressed ferroptosis phenotype in CYP4V2 mutated RPE. Oral administration of DFP also restored the retinal function and morphology in Cyp4v3 KO mice. CONCLUSION: This study represented the first evidence of the substantial role of ferroptosis in the development of BCD. PUFAs resulting from CYP4V2 mutation may serve as substrates for ferroptosis, potentially working in conjunction with NCOA4-regulated iron accumulation, ultimately leading to RPE degeneration. DFP administration, which chelates iron, has demonstrated its ability to reverse BCD phenotype both in vitro and in vivo, suggesting a promising therapeutic approach in the future.

Catechol compounds as dual-targeting agents for fish protection against Ichthyophthirius multifiliis infections.

Aquaculture is one of the fastest growing sectors in global food production, recognized as a significant contributor to poverty alleviation, food security, and income generation. However, the frequent occurrence of diseases caused by pathogen infections result in reduced yields and economic losses, posing a substantial constraint to the sustainable development of aquaculture. Here, our study identified that four catechol compounds, quercetin, luteolin, caffeic acid, and chlorogenic acid, exhibited potent antiparasitic effects against Ichthyophthirius multifiliis in both, in vitro and in vivo. The parasite is recognized as one of the most pathogenic to fish worldwide. Using a combination of in silico methods, the dipeptidyl peptidase (DPP) was identified as a critical target for catechol compounds. The two hydroxyl radicals of the catechol group were essential for its binding to and interacting with the DPP protein. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that catechol compounds disrupt pathways associated with the metabolism and growth of I. multifiliis, thereby exerting antiparasitic effects. Furthermore, these compounds attenuated the expression of proinflammatory cytokines in vivo in fish and promoted macrophage polarization toward M2 phenotype by inhibiting the STAT1 signaling pathway. The dual activity of catechol compounds, acting as both direct antiparasitic and anti-inflammatory agents in fish, offers a promising therapeutic approach for combating I. multifiliis infections in aquaculture.

Partner-Involved Financial Incentives for Smoking Cessation in Dual-Smoker Couples: A Randomized Pilot Trial.

INTRODUCTION: Members of dual-smoker couples (in which both partners smoke) are unlikely to try to quit smoking and are likely to relapse if they do make an attempt. The purpose of this study was to investigate the feasibility, tolerability, and preliminary outcomes of dyadic adaptations of financial incentive treatments (FITs) to promote smoking cessation in dual-smoker couples. AIMS AND METHODS: We enrolled 95 dual-smoker couples (N = 190) in a three-arm feasibility RCT comparing two partner-involved FITs (single vs. dual incentives) against a no-treatment control condition. Participants in all conditions were offered nicotine replacement and psychoeducation. A 3-month follow-up provided information about retention, tolerability (ie, self-reported benefits and costs of the study), and preliminary efficacy (ie, program completion, quit attempts, point-prevalent abstinence, and joint quitting). RESULTS: Results suggest dyadic adaptations were feasible to implement (89% retention rate) and highly tolerable for participants (p < .001). Neither feasibility nor tolerability varied across the treatment arm. Preliminary efficacy outcomes indicated partner-involved FITs have promise for increasing smoking cessation in dual-smoker couples (OR = 2.36-13.06). CONCLUSIONS: Dyadic implementations of FITs are feasible to implement and tolerable to participants. IMPLICATIONS: The evidence that dyadic adaptations of FITs were feasible and tolerable, and the positive preliminary efficacy outcomes suggest that adequately powered RCTs formally evaluating the efficacy of dyadic adaptations of FITs for dual-smoker couples are warranted.

Optimal dose and type of exercise to improve depressive symptoms in older adults: a systematic review and network meta-analysis.

BACKGROUND: Depression is a prevalent issue among older adults, affecting their quality of life and overall well-being. Exercise is an effective means of relieving depressive symptoms in older adults, but the optimal dose for different exercise types remains unclear. As such, the aim of this meta-analysis was to examine the dose-response relationship between overall and specific types of exercise with depression symptoms in older adults. METHODS: This systematic review and network meta-analysis included a search of PubMed, Medline, Embase, PsycINFO, Cochrane library, and Web of Science for randomized controlled trials of exercise in older adults with depression symptoms from inception to 15 July 2023. Comprehensive data extraction covered dose, treatment regimen, demographics and study duration. Dosage metrics, encompassing METs-min/week, were scrutinized in correlation with the Minimal Clinically Importance Difference (MCID). RESULTS: A total of 47 studies involving 2895 participants and 7 kinds of exercise were included in the review. Without considering the dose, the results of our network meta-analysis indicated that Walking was the most effective in alleviating depression in older adults, in addition to Aerobic exercise (AE), Yoga, Qigong, Resistance training (RT), and Tai Chi (TC), which were equally effective. However, the results of the dose-response analysis found that Aerobic exercise was most effective at a dose of 1000 METs-min/week. It is noteworthy that Walking is significantly effective in alleviating depressive symptoms in older adults at very low doses. In terms of clinical benefits, we found that overall exercise doses in the range of 600 ~ 970 METs-min/week were clinically effective. Considering the specific types of exercise, Aerobic exercise, Resistance training, Walking, and Yoga were found to be effective at doses ranging from 820 ~ 1000 METs-min/week, 520 ~ 1000 METs-min/week, 650 ~ 1000 METs-min/week, 680 ~ 1000 METs-min/week, respectively. At the same time, we found that when the age exceeded 81 years, even when participating in exercise, it did not achieve the effect of alleviating depressive symptoms in older adults. CONCLUSIONS: In conclusion, including Walking, AE, Yoga, Qigong, RT, and TC, effectively alleviate depressive symptoms in older adults. Furthermore, we established statistically and clinically significant threshold doses for various exercise types. Early initiation of exercise is beneficial, but its efficacy diminishes from the age of 80, and beyond 81, exercise no longer significantly alleviates depressive symptoms.

Diastasis Recti Abdominis: A Practical and Effective Width-Length Classification Based on Ultrasound Measurements and its Clinical Validation.

OBJECTIVES: This study aimed to establish a simple and practical classification to guide the clinical treatment of diastasis recti abdominis (DRA) based on ultrasound characteristics with different severities of DRA, and to verify its clinical utility. METHODS: We retrospectively enrolled 301 DRA patients as pilot cohort and divided into Conservative Treatment Group and Surgical Group according to clinical outcomes. A new Width-Length classification was summarized based on ultrasound measurements of the width and length of midline separation. Then, 100 DRA patients were enrolled prospectively as validation cohort, and diagnostic performance was evaluated by clinical treatment. RESULTS: The Width-Length classification in pilot cohort was as follows: Type 1 (n = 108), open only at M3; Type 2 (n = 63), open at M3 and either M2 or M4 (inter-rectus distance at M3 <47 mm); Type 3 (n = 44), open at M3 and either M2 or M4 (inter-rectus distance at M3 ≥47 mm); Type 4 (n = 74), open at M3, along with other two sites of M1, M2, M4, or M5; Type 5 (n = 12), open at M2, M3, and M4, along with M1 or M5, or both. DRA patients in Type 1-2 were recommended for conservative treatment, and in Type 3-5 were recommended for surgical treatment (all P < .05). In the validation cohort, the accuracy of Width-Length classification in determining treatment strategy was 86.0%. CONCLUSIONS: This study proposes a Width-Length classification based on the width and length of midline separation on ultrasound, which was validated to be simple, practical and effective in guiding DRA treatment.

Genetic Analysis of 1p36 Deletions for Six Aborted Fetuses.

Context: Chromosomal abnormalities in embryos are the most common cause of early spontaneous abortions. Chromosome 1p36 deletion syndrome (OMIM 607872) is the most common subtelomeric, terminal microdeletion syndrome. Objective: The study intended to analyze miscarriage samples using chromosomal microarray analysis (CMA), to explore the mechanism of chromosomal aberrations, and to identify the recurrence risk and a prenatal diagnostic strategy for couples experiencing spontaneous abortions. Design: The research team performed a narrative review by searching PubMed databases. The search used the keywords 1p36 deletion, CMA, karyotype analysis, FISH and aborted fetus. The team also conducted case studies using genetic analyses. Setting: The study took place at Wuxi Maternity and Child Health Care Hospital in Wuxi, Jiangsu, PR China. Participants: Out of 673 abortion samples, six had 1p36 deletions (0.89%). Participants were the six families who had had those spontaneous abortions. Outcome Measures: The research team evaluated the fetal samples using: (1) CMA, (2) karyotype analysis, and (3) novel fluorescence in-situ hybridization (FISH). Results: The CMA showed that: (1) fetus 1 had a 1.75 MB microdeletion at the 1p36.32p36.31 band, which testing didn't detect in fetus 1's parents, but the research team couldn't exclude the possibility that one of the parents was a carrier of a chromosomal insertional translocation; and (2) fetus 2 had a 5.10 MB microdeletion at the 1p36.13p36.12 segment, and fetus 3 had a 9.21 MB deletion at the 1p36.33p36.22 band, and the high-resolution karyotype analysis and FISH of the parents of both fetuses appeared normal, indicating that the chromosomal abnormalities were de novo; (3) fetus 4 had a 9.28 MB deletion at 1p36.33p36.22, although the high-resolution karyotype analysis of fetus 4's parent was normal; (4) fetuses 5 and 6 had a 7.64 MB microdeletion at 1p36.33p36.23 and a 4.45 MB deletion at 1p36.33p36.32, respectively, although the parents of both fetuses waived further testing. Conclusions: This study provides the first report of recurrent spontaneous and sporadic abortions with 1p36 deletion syndrome. The CMA combined with a reasonable family-pedigree investigation can detect cryptic chromosomal aberrations in miscarriages and can determine the mechanism of the chromosomal variations. It thus is invaluable in assessing recurrence risk and providing appropriate prenatal diagnostic strategies for affected families.

Aqueous humor protein markers in myopia: a review.

PURPOSE: Myopia is one of the most common forms of refractive error. Most myopia manifests itself as a relative growth of the eye axis, resulting in a state in which light is projected in front of the retina after being refracted by the refractive system of the eyeball. So far, the specific pathogenesis of myopia is still not well explained, through the results of animal experiments, researchers have proposed various possible scenarios, but all these are based on animal models, and there may still be a certain gap with the mechanism of true myopia in humans. The most readily available in clinical work is aqueous humor obtained during cataract surgery, for which we reviewed these studies of aqueous humor samples from myopic patients. METHODS: A systematic literature search was done on PubMed using key words including "myopia," "aqueous humor," and "protein." RESULTS: The results of existing aqueous humor studies have shown that the difference in substances in the aqueous humor of myopia is related to the degradation of the scleral matrix, chronic inflammation of the eye, pro-fibrosis, blood vessel production, and inhibition. There may be more than one reason associated with myopia progression. CONCLUSION: The specific mechanism of myopia has not been fully elucidated. Therefore, the means of preventing and treating myopia should focus on inhibiting the degradation of the scleral matrix, promoting the proliferation of scleral collagen fibers, and alleviating chronic inflammation of the eyes. Further research into myopic aqueous humor may provide us with new insights.

[Effects of organic fertilizer from traditional Chinese medicine residues on growth and soil microbial community of Salvia miltiorrhiza by metagenomic technique].

Soil microbiome is a key evaluation index of soil health. Previous studies have shown that organic fertilizer from traditional Chinese medicine(TCM)residues can improve the yield and quality of cultivated traditional Chinese medicinal materials. However, there are few reports on the effects of organic fertilizer from TCM residues on soil microbiome. Therefore, on the basis of evaluating the effects of organic fertilizer from TCM residues on the yield and quality of cultivated Salvia miltiorrhiza, the metagenomic sequencing technique was used to study the effects of organic fertilizer from TCM residues on rhizosphere microbiome community and function of cultivated S. miltiorrhiza. The results showed that:(1) the application of organic fertilizer from TCM residues promoted the growth of S. miltiorrhiza and the accumulation of active components, and the above-ground and underground dry weight and fresh weight of S. miltiorrhiza increased by 371.4%, 288.3%, 313.4%, and 151.9%. The increases of rosmarinic acid and salvianolic acid B were 887.0% and 183.0%.(2)The application of organic fertilizer from TCM residues significantly changed the rhizosphere bacterial and fungal community structures, and the microbial community composition was significantly different.(3)The relative abundance of soil-beneficial bacteria, such as Nitrosospira multiformis, Bacillus subtilis, Lysobacter enzymogenes, and Trichoderma was significantly increased by the application of organic fertilizer from TCM residues.(4)KEGG function prediction analysis showed that metabolism-related microorganisms were more easily enriched in the soil environment after organic fertilizer application. The abundance of functional genes related to nitrification and denitrification could also be increased after the application of organic fertilizer from TCM residues. The results of this study provide guidance for the future application of organic fertilizer from TCM residues in the cultivation of traditio-nal Chinese medicinal materials and enrich the content of green cultivation technology of traditional Chinese medicinal materials.

Yield and Efficiency of a Population-Based Mass Tuberculosis Screening Intervention Among Persons With Diabetes in Jiangsu Province, China.

BACKGROUND: The evidence-base for mass tuberculosis screening among persons with diabetes (PWD) is poor. We evaluated the yield and costs of mass screening among PWD in eastern China. METHODS: We included individuals with type 2 diabetes from 38 townships in Jiangsu Province. Screening comprised of physical examinations, symptom screening, and chest X-rays; smear and culture testing were performed through clinical triage. We assessed the yield and number needed to screen (NNS) to detect 1 tuberculosis case among all PWD, those with symptoms, and with suggestive chest X-rays. Unit costing was collected to estimate screening costs and to calculate cost per case detected. We performed a systematic review of other mass tuberculosis screening programs concentrated on PWD. RESULTS: Of 89 549 screened PWD, 160 were diagnosed with tuberculosis (179 cases per 100 000 persons; 95% confidence interval [CI]: 153-205). The NNS was 560 (95% CI: 513-606), 248 (95% CI: 217-279), and 36 (95% CI: 24-48) among all participants, with abnormal chest X-rays, and symptoms. The cost per case was high overall (US$13 930) but lower with symptoms (US$1037) and high fasting blood glucose levels (US$6807). From systematic review, the pooled NNS to detect one case among all PWD (regardless of symptoms or chest X-ray results) in high- versus low-burden settings was 93 (95% CI: 70-141) versus 395 (95% CI: 283-649). CONCLUSIONS: A mass tuberculosis screening program focused on PWD was feasible however, the overall yield was low and not cost-efficient. Risk-stratified approaches may be practical among PWD in low- and medium tuberculosis burden settings.

Effect of Norovirus Inoculum Dose on Virus Kinetics, Shedding, and Symptoms.

The effect of norovirus dose on outcomes such as virus shedding and symptoms after initial infection is not well understood. We performed a secondary analysis of a human challenge study by using Bayesian mixed-effects models. As the dose increased from 4.8 to 4,800 reverse transcription PCR units, the total amount of shed virus in feces increased from 4.5 × 1011 to 3.4 × 1012 genomic equivalent copies; in vomit, virus increased from 6.4 × 105 to 3.0 × 107 genomic equivalent copies. Onset time of viral shedding in feces decreased from 1.4 to 0.8 days, and time of peak viral shedding decreased from 2.3 to 1.5 days. Time to symptom onset decreased from 1.5 to 0.8 days. One type of symptom score increased. An increase in norovirus dose was associated with more rapid shedding and symptom onset and possibly increased severity. However, the effect on virus load and shedding was inconclusive.

Age-related model for estimating the symptomatic and asymptomatic transmissibility of COVID-19 patients.

Estimation of age-dependent transmissibility of COVID-19 patients is critical for effective policymaking. Although the transmissibility of symptomatic cases has been extensively studied, asymptomatic infection is understudied due to limited data. Using a dataset with reliably distinguished symptomatic and asymptomatic statuses of COVID-19 cases, we propose an ordinary differential equation model that considers age-dependent transmissibility in transmission dynamics. Under a Bayesian framework, multi-source information is synthesized in our model for identifying transmissibility. A shrinkage prior among age groups is also adopted to improve the estimation behavior of transmissibility from age-structured data. The added values of accounting for age-dependent transmissibility are further evaluated through simulation studies. In real-data analysis, we compare our approach with two basic models using the deviance information criterion (DIC) and its extension. We find that the proposed model is more flexible for our epidemic data. Our results also suggest that the transmissibility of asymptomatic infections is significantly lower (on average, 76.45% with a credible interval (27.38%, 88.65%)) than that of symptomatic cases. In both symptomatic and asymptomatic patients, the transmissibility mainly increases with age. Patients older than 30 years are more likely to develop symptoms with higher transmissibility. We also find that the transmission burden of asymptomatic cases is lower than that of symptomatic patients.

Measuring bereavement prevalence in a complex sampling survey: the 2019 Georgia Behavioral Risk Factor Surveillance System (BRFSS).

BACKGROUND: The Behavioral Risk Factor Surveillance System (BRFSS) is an annual survey designed to identify trends in the public's health. In its 2019 field survey, the U.S. state of GA tested a new 3 - item module to measure the numbers of bereaved, resident adults aged 18 years and older. Participants were eligible if they answered 'Yes' to the item 'Have you experienced the death of a family member or close friend in the years 2018 or 2019?'. This analysis explores two research questions. Can estimates for bereavement prevalence be derived without large sampling errors, low precision, and small subsamples? Can multiple imputation techniques be applied to overcome non-response and missing data to support multivariate modeling? METHODS: BRFSS is a non-institutionalized sample of adults aged 18 years and older living in the U.S. state of Georgia. Analyses in this study were conducted under two scenarios. Scenario 1 applies the complex sample weights created by the Centers for Disease Control and imputes values for missing responses. Scenario 2 treats the data as a panel - no weighting combined with removal of persons with missing data. Scenario 1 reflects the use of BRFSS data for public health and policy, while Scenario 2 reflects data as it is commonly used in social science research studies. RESULTS: The bereavement screening item has a response rate (RR) of 69.1% (5206 of 7534 persons). Demographic subgroups and categories of health have RR of 55% or more. Under Scenario 1, the estimated prevalence of bereavement is 45.38%, meaning that 3,739,120 adults reported bereaved in 2018 or 2019. The estimated prevalence is 46.02% with Scenario 2 which removes persons with any missing data (4,289 persons). Scenario 2 overestimates the bereavement prevalence by 1.39%. An illustrative logistic model is presented to show the performance of exposure to bereavement under the two data scenarios. CONCLUSIONS: Recent bereavement can be ascertained in a surveillance survey accounting for biases in response. Estimating bereavement prevalence is needed for measuring population health. This survey is limited to one US state in a single year and excludes persons aged 17 years and younger.

Nucleation kinetics model for primary crystallization in Al-Y-Fe metallic glass.

The high density of aluminum nanocrystals (>1021 m-3) that develop during the primary crystallization in Al-based metallic glasses indicates a high nucleation rate (∼1018 m-3 s-1). Several studies have been advanced to account for the primary crystallization behavior, but none have been developed to completely describe the reaction kinetics. Recently, structural analysis by fluctuation electron microscopy has demonstrated the presence of the Al-like medium range order (MRO) regions as a spatial heterogeneity in as-spun Al88Y7Fe5 metallic glass that is representative for the class of Al-based amorphous alloys that develop Al nanocrystals during primary crystallization. From the structural characterization, an MRO seeded nucleation configuration is established, whereby the Al nanocrystals are catalyzed by the MRO core to decrease the nucleation barrier. The MRO seeded nucleation model and the kinetic data from the delay time (τ) measurement provide a full accounting of the evolution of the Al nanocrystal density (Nv) during the primary crystallization under isothermal annealing treatments. Moreover, the calculated values of the steady state nucleation rates (Jss) predicted by the nucleation model agree with the experimental results. Moreover, the model satisfies constraints on the structural, thermodynamic, and kinetic parameters, such as the critical nucleus size, the interface energy, and the volume-free energy driving force that are essential for a fully self-consistent nucleation kinetics analysis. The nucleation kinetics model can be applied more broadly to materials that are characterized by the presence of spatial heterogeneities.

Correlation analysis of aqueous humor metabolomics with myopic axial length and choroidal parameters.

BACKGROUND: To explore differential metabolites in the aqueous humor of patients with different axial lengths and their correlations with axial length and choroidal parameters. METHODS: In this study, we included 12 patients with axial lengths less than 24 mm, 11 patients with axial lengths between 24 and 26 mm, and 11 patients with axial lengths greater than 26 mm. We collected their aqueous humor samples during cataract surgery for liquid chromatography-mass spectrometry metabolomic analysis. Simultaneously, we collected relevant clinical parameters such as axial length, subfoveal choroidal thickness, and choroidal vascular index. Correlations between clinical data, differential metabolites, and clinical indicators were analyzed. In addition, we plotted receiver operating characteristic curves. RESULTS: The results showed that axial length was significantly negatively correlated with choroidal thickness (r=-0.7446, P < 0.0001), and that several differential metabolites were significantly correlated with certain clinical parameters. After analyzing receiver operating characteristic curves, 5-methoxytryptophol and cerulenin were found to have excellent discriminative power, demonstrating their potential as biomarkers. In the enrichment analysis, we found that the differential metabolites among each group were involved in several special pathways (Taurine and Hypotaurine Metabolism, Vitamin B6 Metabolism, Pantothenate, and coenzyme A Biosynthesis), suggesting that abnormalities in these metabolic pathways may play a role in the process of axial myopia. CONCLUSIONS: Our study identified alterations in certain metabolic pathways in different axial lengths. At the same time, we found several metabolites with significant correlation with clinical indicators, among which 5-methoxytryptophol and cerulenin were associated with axial myopia. CLINICAL TRIAL REGISTRATION: Registration date:11/04/2022. TRIAL REGISTRATION NUMBER: ChiCTR2200058575. TRIAL REGISTRY: The First Affiliated Hospital of the Zhejiang University School of Medicine.