A body map of somatic mutagenesis in morphologically normal human tissues.

Somatic mutations that accumulate in normal tissues are associated with ageing and disease1,2. Here we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies of 9 organs from 5 donors. We found that somatic mutation accumulations and clonal expansions were widespread, although to variable extents, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for in tissues from the oesophagus and cardia. Endogenous mutational processes with the SBS1 and SBS5 mutational signatures are ubiquitous among normal tissues, although they exhibit different relative activities. Exogenous mutational processes operate in multiple tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimetre resolution. In the oesophagus and cardia, macroscopic somatic clones that expanded to hundreds of micrometres were frequently seen, whereas in tissues such as the colon, rectum and duodenum, somatic clones were microscopic in size and evolved independently, possibly restricted by local tissue microstructures. Our study depicts a body map of somatic mutations and clonal expansions from the same individual.

PancanQTLv2.0: a comprehensive resource for expression quantitative trait loci across human cancers.

Expression quantitative trait locus (eQTL) analysis is a powerful tool used to investigate genetic variations in complex diseases, including cancer. We previously developed a comprehensive database, PancanQTL, to characterize cancer eQTLs using The Cancer Genome Atlas (TCGA) dataset, and linked eQTLs with patient survival and GWAS risk variants. Here, we present an updated version, PancanQTLv2.0 (https://hanlaboratory.com/PancanQTLv2/), with advancements in fine-mapping causal variants for eQTLs, updating eQTLs overlapping with GWAS linkage disequilibrium regions and identifying eQTLs associated with drug response and immune infiltration. Through fine-mapping analysis, we identified 58 747 fine-mapped eQTLs credible sets, providing mechanic insights of gene regulation in cancer. We further integrated the latest GWAS Catalog and identified a total of 84 592 135 linkage associations between eQTLs and the existing GWAS loci, which represents a remarkable ∼50-fold increase compared to the previous version. Additionally, PancanQTLv2.0 uncovered 659516 associations between eQTLs and drug response and identified 146948 associations between eQTLs and immune cell abundance, providing potentially clinical utility of eQTLs in cancer therapy. PancanQTLv2.0 expanded the resources available for investigating gene expression regulation in human cancers, leading to advancements in cancer research and precision oncology.

Assessing family function: older adults vs. care nurses: a cross-sectional comparative study.

BACKGROUND: This study aimed to assess family function in home care for older adults. Understanding family dynamics is essential for providing quality care to older adults choosing to age in place. METHODS: In a cross-sectional study, 53 patients aged 65 or older receiving home care were evaluated, along with four home care nurses. The General Function of Family Assessment Device (FAD-GF) was used for self-assessment to examine family resources. RESULTS: Only 5.7% of older adults reported good family function. Strong correlations were found between assessments by nurses and older adults. Among the six aspects of family function, "problem solving," "communication," "affective responsiveness," and the overall results showed no disparities between the evaluations of older adults and nurses. CONCLUSIONS: Home care nurses can effectively assess family function using the FAD-GF, particularly after six months of care. This assessment can help identify family issues and enhance home care quality through nurse training in FAD-GF application.

Development of a long-term care service integration self-assessment tool.

The World Health Organization emphasizes the importance of providing integrated care for older people. Taiwan is the fastest aging country in the world. In 2016, Taiwan implemented the Long-Term Care Plan 2.0 (TLTCP 2.0), aimed at providing integrated long-term care (LTC) services in communities. However, LTC service agencies have not been able to evaluate the level of integrated care they provide due to the lack of an effective assessment tool. To address this need, this study sets out to develop an integration assessment tool, namely the Self-Assessment for Service Integration in Long-Term Care (SASI-LTC), which will allow LTC agencies to self-evaluate their current level of integration from multiple perspectives. The SASI-LTC was developed based on Evashwick's framework, underwent two rounds of Delphi panels with twenty-six experts, and a pilot test with 243 valid questionnaires from administrators of Tier A agencies who are responsible for integrating LTC. The Delphi experts assessed the content with high levels of agreement using medians, the scale content validity index (SCVI) and item content validity index (ICVI). The SASI-LTC included four domains (inter-entity organization and management, integrated care coordination, integrated resources, and integrated information systems) with thirty items. The SASI-LTC showed good reliability (Cronbach's α = 0.94) and good validity, and a confirmatory factor analysis showed a good model fit index [χ2/df = 1.38; RMSEA = 0.040; CFI = 0.963; SRMR = 0.049] in pilot testing. While the SASI-LTC is a useful and feasible tool for Taiwan's LTC service agencies to evaluate their level of integration in providing LTC services, it could also be used in other countries with minor adjustments to localization of items related to financial integration.

Addition of ruxolitinib in Graft-versus-Host disease prophylaxis for pediatric ß-Thalassemia major patients after allogeneic stem cell transplantation: A retrospective cohort study.

BACKGROUND: To evaluate the effect of addition of ruxolitinib in Graft-versus-Host Disease (GVHD) prophylaxis on pediatric patients with ß-thalassemia major after allogeneic hematopoietic stem cell transplantation(HSCT). METHODS: This retrospective study reviewed 49 consecutive ß-thalassemia major pediatric patients who underwent HSCT from unrelated or haploidentical donors from February 2018 to October 2022. All transplantation recipients received cyclosporine A (CsA), mycophenolate mofetil (MMF), and short-term methotrexate (MTX) as GVHD prophylaxis; while 27 of them in the ruxolitinib group had added ruxolitinib oral to GVHD prophylaxis regimen at 2.5 mg twice daily once successful engraftment after January 2020. RESULTS: The outcome showed that the ruxolitinib group had a lower cumulative incidence than the control group regardless of acute GVHD (22.2% vs.40.9%; p = .153) or chronic GVHD (18.5% vs.40.9%; p = .072); especially, the incidence of grade III-IV acute GVHD was reported significantly less frequently in ruxolitinib group than that of the control group (0 vs. 27.3%, p = .005). No significant difference was detected between the two groups in EBV (Epstein-Barr virus)/CMV (cytomegalovirus) reactivation and BKV (BK virus) infection (p = .703, 1.000, and .436, respectively). Twenty-six patients (96.3%) in the ruxolitinib group were alive, while two patients (9.1%) in the control group died of intestinal acute GVHD. The 2-year overall survival (OS) and thalassemia-free survival (TFS) were both 96.296% in the ruxolitinib group, while both 90.909% in the control group. CONCLUSION: This study reveals that ruxolitinib prophylaxis is a promising option to decrease the incidence of grade III-IV acute GVHD in pediatric patients with ß-thalassemia major.

Diversity and potential functional characteristics of phage communities colonizing microplastic biofilms.

The multiple ecological influences and potential microbial degradation of microplastics are generally attributed to the microbial communities colonized on microplastics. Phages play an important role in the composition and function of their bacterial hosts, yet the occurrence and the potential functional characteristics of phages in the biofilms of microplastics have not been known. This study, for the first time, explored the diversity, composition, and potential function characteristics of phage communities living in the biofilms of PP, PE, and PET microplastics and stones, cultured in the same site, via the metagenome method. The results showed that a total of 240 non-redundant virus OTUs (vOTUs), distributed in at least four orders and seven families, were detected from biofilm metagenomes of microplastics. Compared to stones, some phages were selectively enriched by microplastic biofilms, with 13 vOTUs uniquely colonized on three microplastics, and these vOTUs mainly belong to the family Autographiviridae and Podoviridae. Except for the evenness of PP, the richness index, Chao 1 index, and abundance of phage communities of three microplastics were much higher than that of stone. At least 8 bacterial phyla and 72 genera were possibly infected by phages. Compared to the stones, both composition and abundance of the phages and hosts presented significant and strong correlations for three microplastics. Some of the bacterial hosts on microplastics were likely involved in the microplastic degradation, fermenters, nitrogen transformation processes, and so on. A total of 124 encoding auxiliary metabolic genes (AMGs) were detected from viral contigs. The abundance of AMGs in microplastics was much higher than that of stones, which may provide more direct or indirect support for the bacterial degradation of microplastics. This study provides a new perspective on the occurrence and potential functions of phages on microplastic biofilms, thus expanding our understanding of microbial communities on microplastic biofilms.

Effects of social capital on healthcare utilization among older adults in Indonesia.

Social capital potentially affects older adults' access to healthcare services. However, the effects of social capital on the use of various types of healthcare services using longitudinal data have yet to be explored. This study aimed to examine the effects of structural and cognitive social capital on different types of healthcare utilization by older adults in Indonesia. Data were from the Indonesian Family Life Survey (waves 4 and 5) in 2007 and 2014. The sample consisted of participants aged 60 years and older who completed both waves (n = 1374). Healthcare utilization by older adults assessed health posts (posyandu), health checkups, outpatient care and hospital admissions. Social capital consisted of neighborhood trust and community participation. Generalized estimating equation models were used for the analysis. Older adults with high community participation had a higher likelihood of using preventive care in posyandu (OR = 5.848, 95% CI = 2.585-13.232) and health checkup visits (OR = 1.621, 95% CI = 1.116-2.356). Meanwhile, neighborhood trust was related to a higher probability of hospital admissions (OR = 1.255, 95% CI = 1.046-1.505). Social capital significantly affects older adults' preventive and treatment healthcare utilization. Maximizing the availability of social participation and removing barriers to access to preventive and medical care in an age-friendly environment are suggested.

Relationship between indwelling site and peripheral venous catheter-related complications in adult hospitalized patients: A systematic review and meta-analysis.

AIMS AND OBJECTIVES: This systematic review and meta-analysis aimed to compare the incidence of PVC-related complications between catheterisation in the forearm and back of the hand in adult patients. BACKGROUND: A peripheral intravenous catheter (PVC) is often inserted as part of care during patients' hospitalisation. The catheter is typically inserted in the forearm or at the back of the hand in usual practice. Studies have not yet reached a consensus on the optimal insertion site in any clinical setting. DESIGN: We performed a systematic review and meta-analysis based on PRISMA guidelines. METHODS: We searched the following electronic databases: PubMed, Cochrane Library, Embase, and CINAHL. Randomised controlled trials, cohort studies, case-control studies and cross-sectional studies from inception to July 2021 reporting the incidence of PVC-related complications at the forearm and back of the hand were included. Fixed-effects models and random-effects models were used to derive the pooled risk ratios. RESULTS: Twenty-four studies involving 16562 PVCs met our inclusion criteria. The meta-analysis showed that compared with PVC placement in the back of the hand, placement in the forearm was associated with a higher incidence of total complications and infiltration/extravasation. However, the differences between the PVC indwelling sites were not significant (total complications: P = 0.43; phlebitis: P = 0.35; infiltration/extravasation: P = 0.51). Both incidence of total complications and infiltration/extravasation analyses showed high heterogeneity (total complications: I2  = 60%; infiltration/extravasation: I2  = 58%). CONCLUSION: Available evidence suggests that there is no significant difference between PVC placement in the forearm and at the back of the hand in terms of the incidence of complications, thus making both approaches suitable. RELEVANCE TO CLINICAL PRACTICE: For patients who need indwelling PVC, medical staff can choose the best indwelling site, and both forearm and back of the hand are suitable.

Differing determinants of disability trends among men and women aged 50 years and older.

BACKGROUND: Researchers have emphasized the importance of examining how different factors affect men's and women's functional status over time. To date, the literature is unclear about whether sex affects the rate of change in disability in middle to older age. Researchers have further emphasized the importance of examining how different factors affect men's and women's functional status over time. We examined (a) sex differences in disability trends and (b) the determinants of the rate of change in disability for men and women 50 years and older. METHODS: This study utilized the Taiwan Longitudinal Study on Aging Survey, a nationally representative database (four waves of survey data 1996-2007, N = 3429). We modeled and compared the differences in disability trends and the influences of determinants on trends among men and women using multiple-indicator and multiple-group latent growth curves modeling (LGCM). Equality constraints were imposed on 10 determinants across groups. RESULTS: Once disability began, women progressed toward greater disability 18% faster than men. Greater age added about 1.2 times the burden to the rate of change in disability for women than men (p < 0.001). More comorbidities also added significantly more burden to baseline disability and rate of change in disability among women than men (p < 0.001), but women benefited more from higher education levels in lower baseline disability and slower rate of change. Having a better social network was associated with lower baseline disability among women only (p < 0.05). For both men and women, physically active leisure-time activities were beneficial in lower baseline disability (p men and women < 0.001) and rate of change in disability (p men < 0.01; p women < 0.05), with no significant differences between groups. CONCLUSIONS: Age may widen the sex gap in the rate of change in disability. However, both sexes benefit from participating in leisure-time activities. Promoting health literacy improves health outcomes and physical function among women.

Porcine epidemic diarrhea virus infection induces endoplasmic reticulum stress and unfolded protein response in jejunal epithelial cells of weaned pigs.

Porcine epidemic diarrhea virus (PEDV) infection leads to diarrhea and subsequently to decreased feed efficiency and growth in weaned pigs. Given that few studies have addressed the host-virus interaction in vivo, this study focused on endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in jejunal epithelial cells during PEDV infection. Eight-week-old pigs (n = 64) were orally inoculated with PEDV IN19338 strain (n = 40) or sham-inoculated (n = 24) and analyzed for PEDV viral RNA shedding using reverse transcription-quantitative polymerase chain reaction and for viral antigen within enterocytes using immunohistochemistry (IHC). ER stress was analyzed in a subset of 9 PEDV-inoculated pigs with diarrhea, detectable viral RNA, and viral antigen (PEDV-immunopositive pigs). Compared with control pigs, PEDV-immunopositive pigs had a reduced ratio of villus height to crypt depth in the jejunum (P = .002, n = 9 per group), consistent with intestinal injury. The protein levels of ATF6, IRE1, PERK, XBP1u, ATF4, GRP78, and caspase-3 were assessed in jejunal epithelial cells at the villus tips via IHC. Both ER stress and UPR were demonstrated in PEDV-immunopositive pigs by the increased expression of ATF6 (P = .047), IRE1 (P = .007), and ATF4 (P = .001). The expression of GRP78 (P = .024) and caspase-3 (P = .004) were also increased, indicating an accompanying increase in ER protein folding capacity and apoptosis. Overall, these results reveal that PEDV infection induces ER stress and UPR in intestinal epithelial cells of weaned pigs.

Determinants associated with medical-related long-term care service use among community-dwelling older adults in Taiwan.

INTRODUCTION: Medical-related long-term care (LTC) service use among community-dwelling older adults in Taiwan is resource-intensive, and planning is essential to promote aging-in-place. METHODS: Administrative data from 4/1/2017 to 11/26/2019 among more than 14,000 residents were analyzed with generalized estimating equations (GEEs) to identify determinants of medical-related LTC service use. RESULTS: Older adults using medical-related LTC services tended to be younger (79.9 vs. 80.7; p<.0001), male (42.7% vs. 38.5%; p<.0001), multi-morbid (3.1 vs. 2.5; p<.0001), and higher mean activities of daily living (ADL) disability (8.2 vs. 4.2; p<.0001), instrumental ADL (IADL) disability (11.0 vs. 9.1; p<.0001), and hospitalizations (1.1 vs. 0.4; p<.0001). Significant determinants of medical-related LTC services include age, education, stroke, coronary heart disease, diabetes, vision impairment, ADL disability, and prior hospitalization. DISCUSSION: The success of LTC 2.0 will depend on ADL support and care coordination to manage chronic conditions such as diabetes, vision impairment, coronary heart disease, and stroke.

[Berberine hydrochloride inhibits benign prostatic hyperplasia in rats by activating the Nrf2/ARE pathway].

Objective: To study the inhibitory effect of berberine hydrochloride (BBR) on BPH and its underlying mechanism in male rats. METHODS: Forty male rats were randomly divided into a normal control, a BPH model control, a BBR intervention, and a BBR+Bruceol intervention group, and the BPH model was established in the latter three groups. The animals in the normal and BPH model control groups were treated intragastrically with normal saline, and those in the BBR and BBR+Bruceol intervention groups with BBR at 200 mg/kg and BBR plus Bruceol at 1 mg/kg, respectively, once a day for 14 consecutive days. The prostates of the rats were harvested for measurement of their wet weight and prostatic index, detection of the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) and determination of the protein expressions of nuclear factor E2-related factor 2 (Nrf2), antioxidant response element (ARE) and reduced coenzyme I quinone oxidoreductase (NQO1) in the prostate tissue by Western blot. RESULTS: The wet weights of the prostate in the normal control, BPH model control, BBR intervention, and BBR+Bruceol intervention groups were (715.63 ± 28.57) mg, (1118.93 ± 36.41) mg, (896.21 ± 20.24) mg and (967.23 ± 24.98) mg, the prostate indexes were 2.10 ± 0.13, 3.45 ± 0.22, 2.75 ± 0.19 and 3.01 ± 0.14, the SOD contents in the prostate tissue were (38.54 ± 5.12) U/mg, (13.98 ± 2.01) U/mg, (26.75 ± 3.19) U/mg and (20.16 ± 4.10) U/mg, and the MDA contents were (3.59 ± 0.83) nmol/mg, (12.63 ± 3.26) nmol/mg, (7.20 ± 1.69) nmol/mg and (9.85 ± 1.71) nmol/mg, respectively. The relative expressions of the Nrf2 protein in the four groups were 0.53 ± 0.06, 0.12 ± 0.03, 0.36 ± 0.04 and 0.25 ± 0.03, those of the ARE protein were 0.69 ± 0.07, 0.21 ± 0.02, 0.50 ± 0.06 and 0.30 ± 0.04, and those of the NQO1 protein were 0.44 ± 0.05, 0.15 ± 0.03, 0.30 ± 0.04 and 0.22 ± 0.03, respectively. There were statistically significant differences in all the above indicators between the normal and BPH model control groups (P < 0.05), as well as between the BPH model control and BBR intervention groups (P < 0.05) and between the BPH model control and the BBR+Bruceol intervention groups (P < 0.05). CONCLUSIONS: BBR hydrochloride can inhibit prostatic hyperplasia in BPH rats and reduce oxidative stress and pathological changes by activating the Nrf2/ARE pathway.

Pirfenidone modulates macrophage polarization and ameliorates radiation-induced lung fibrosis by inhibiting the TGF-ß1/Smad3 pathway.

Radiation-induced lung injury (RILI) mainly contributes to the complications of thoracic radiotherapy. RILI can be divided into radiation pneumonia (RP) and radiation-induced lung fibrosis (RILF). Once RILF occurs, patients will eventually develop irreversible respiratory failure; thus, a new treatment strategy to prevent RILI is urgently needed. This study explored the therapeutic effect of pirfenidone (PFD), a Food and Drug Administration (FDA)-approved drug for (IPF) treatment, and its mechanism in the treatment of RILF. In vivo, C57BL/6 mice received a 50 Gy dose of X-ray radiation to the whole thorax with or without the administration of PFD. Collagen deposition and fibrosis in the lung were reversed by PFD treatment, which was associated with reduced M2 macrophage infiltration and inhibition of the transforming growth factor-ß1 (TGF-ß1)/Drosophila mothers against the decapentaplegic 3 (Smad3) signalling pathway. Moreover, PFD treatment decreased the radiation-induced expression of TGF-ß1 and phosphorylation of Smad3 in alveolar epithelial cells (AECs) and vascular endothelial cells (VECs). Furthermore, IL-4-induced M2 macrophage polarization and IL-13-induced M2 macrophage polarization were suppressed by PFD treatment in vitro, resulting in reductions in the release of arginase-1 (ARG-1), chitinase 3-like 3 (YM-1) and TGF-ß1. Notably, the PFD-induced inhibitory effects on M2 macrophage polarization were associated with downregulation of nuclear factor kappa-B (NF-κB) p50 activity. Additionally, PFD could significantly inhibit ionizing radiation-induced chemokine secretion in MLE-12 cells and consequently impair the migration of RAW264.7 cells. PFD could also eliminate TGF-ß1 from M2 macrophages by attenuating the activation of TGF-ß1/Smad3. In conclusion, PFD is a potential therapeutic agent to ameliorate fibrosis in RILF by reducing M2 macrophage infiltration and inhibiting the activation of TGF-ß1/Smad3.

Effect of chemoradiotherapy on the proportion of circulating lymphocyte subsets in patients with limited-stage small cell lung cancer.

OBJECTIVE: Chemoradiotherapy (CRT) is the standard treatment for limited-stage small cell lung cancer (LS-SCLC), which can exert anti-tumor effects by regulating immune cells. Different immune cell subsets are associated with a specific sensitivity to CRT. The purpose of this study was to characterize the proportion or composition of peripheral lymphocytes in patients with LS-SCLC before and after CRT, and evaluate their prognostic value. METHODS: A total of 98 patients with LS-SCLC were enrolled. The expression of CD3, CD4, CD8, CD45RA, CD45RO, CD38, CD56, and CD19 on the surface of peripheral blood cells was detected by flow cytometry and retrospectively analyzed. The relationship between the proportion of lymphocyte subsets, progression-free survival (PFS), and overall survival (OS) was evaluated using a log-rank test and Cox regression model. RESULTS: The median PFS was 12.3 months and the median OS was 21.7 months. Compared with the pre-treatment specimens, post-treatment lymphocytes had increased proportions of CD3+, CD3+CD8+, CD8+CD38+ T cells, and NKT cells, and a decreased proportion of CD3+CD4+ T cells, CD4+CD45RA+ T cells, B cells, NK cells, and CD4/CD8 ratio. Univariate and multivariate analyses showed that prophylactic cranial irradiation, high percentages of CD4+CD45RA+, CD8+CD38+ T cells after CRT independently predicted superior PFS. Male patients with a high baseline CD4+CD45RO+ T cell ratio predicted a poor OS. CONCLUSIONS: CRT induced changes in the proportion of circulating lymphocyte subsets in LS-SCLC, which is helpful for designing a regimen of immune drugs to be combined with CRT. The prognostic value of the proportion of lymphocytes aids in understanding the role of peripheral immune profiles in LS-SCLC.

Synergistic effect of PAF inhibition and X-ray irradiation in non-small cell lung cancer cells.

PURPOSE: Proliferating cell nuclear antigen-associated factor (PAF) is involved in cancer cell growth and associated with cell death induced by ultraviolet (UV) radiation. However, the contribution of PAF to radiotherapy sensitivity in non-small cell lung cancer (NSCLC) is unknown. The aim of this study was to investigate the relationship between PAF expression and radiotherapy response in NSCLC. METHODS: Associations between PAF expression and patient survival outcomes were evaluated using publicly available online gene expression datasets. RNA interference was performed to knockdown PAF expression in the NSCLC cells. The effects of PAF knockdown on cell proliferation, migration, apoptosis, DNA damage, and activation of MEK/ERK and Wnt/ß-catenin signaling pathways following X­ray irradiation were evaluated in vitro. RESULTS: PAF was found to be overexpressed in lung cancer tissues compared with normal samples, and elevated PAF expression was significantly correlated with inferior patient survival. In vitro, knockdown of PAF inhibited cell proliferation, cell apoptosis, and migration induced by X­ray irradiation. Moreover, X­ray-induced intracellular DNA strand damage was more obvious following PAF knockdown. Additionally, PAF knockdown inhibited activation of the MEK/ERK and Wnt/ß-catenin signaling pathways in X­ray-irradiated A549 cells. CONCLUSION: These data demonstrate that reduced expression of PAF enhances radiosensitivity in NSCLC cells. Mechanistically, inhibition of the MEK/ERK and Wnt/ß-catenin signaling pathways caused by PAF interference may lead to impaired cell function and enhance sensitivity to X­rays. Targeting PAF may therefore serve as a potential therapeutic strategy to increase the efficiency of radiotherapy in NSCLC patients, ultimately improving patient survival.

Preparedness for containing COVID-19 outbreak in mass religious gathering with non-pharmaceutical interventions (NPIs).

BACKGROUND: The COVID-19 outbreaks associated with mass religious gatherings which have the potential of invoking epidemics at large scale have been a great concern. This study aimed to evaluate the risk of outbreak in mass religious gathering and further to assess the preparedness of non-pharmaceutical interventions (NPIs) for preventing COVID-19 outbreak in this context. METHODS: The risk of COVID-19 outbreak in mass religious gathering was evaluated by using secondary COVID-19 cases and reproductive numbers. The preparedness of a series of NPIs for preventing COVID-19 outbreak in mass religious gathering was then assessed by using a density-dependent model. This approach was first illustrated by the Mazu Pilgrimage in Taiwan and validated by using the COVID-19 outbreak in the Shincheonji Church of Jesus (SCJ) religious gathering in South Korea. RESULTS: Through the strict implementation of 80% NPIs in the Mazu Pilgrimage, the number of secondary cases can be substantially reduced from 1508 (95% CI: 900-2176) to 294 (95% CI: 169-420) with the reproductive number (R) significantly below one (0.54, 95% CI: 0.31-0.78), indicating an effective containment of outbreak. The expected number of secondary COVID-19 cases in the SCJ gathering was estimated as 232 (basic reproductive number (R0) = 6.02) and 579 (R0 = 2.50) for the first and second outbreak, respectively, with a total expected cases (833) close to the observed data on high infection of COVID-19 cases (887, R0 = 3.00). CONCLUSION: We provided the evidence on the preparedness of NPIs for preventing COVID-19 outbreak in the context of mass religious gathering by using a density-dependent model.

A clinical study to assess the gingivitis reduction efficacy of a novel stannous-containing fluoride dentifrice.

PURPOSE: To assess the gingivitis reduction efficacy of a novel stannous-containing fluoride dentifrice relative to a negative control. METHODS: 100 generally healthy adults with 10 or more gingival bleeding sites based on the Mazza Modification of the Papillary Bleeding Index (Mazza GI) were enrolled into a 2-week randomized, controlled, double-blind, single-center, two-treatment, parallel group clinical study. The subjects were randomly assigned to the stannous-containing dentifrice group (experimental group) or the sodium fluoride dentifrice group (negative control group). An oral examination and Mazza GI examination were conducted at Baseline, Day 3 and Week 2 post-baseline by a qualified dental examiner. RESULTS: 98 subjects completed the study. The experimental group provided a significant reduction in Mazza GI scores and number of bleeding sites relative to baseline at Day 3 and Week 2 (P< 0.0001). The negative control did not provide significant reductions versus baseline for either measure at either timepoint (P> 0.3). At Day 3, the experimental group provided a statistically significant reduction of Mazza GI scores and number of bleeding sites compared with the negative control group (P< 0.0001). At Week 2, the experimental group showed 24.11% lower Mazza GI scores and 54.81% fewer bleeding sites than the negative control group (P< 0.0001). CLINICAL SIGNIFICANCE: The results demonstrated that the novel stannous-containing fluoride dentifrice had a superior anti-gingivitis effect compared to the sodium fluoride negative control dentifrice, which was evident as quickly as 3 days after use and further improved after 2 weeks of usage.

Validation of the short falls efficacy scale-international for Taiwanese community-dwelling older adults: Associations with fall history, physical frailty, and quality of life.

The FES-I is widely used to measure the fear of falling. However, studies linking the Chinese version of the FES-I to frailty and quality of life among older adults are still limited. Thus, this study examined the association of the full 16-item FES-I and the 7-item short FES-I with fall history, physical frailty, and quality of life among older Taiwanese adults. A total of 751 community-dwelling older adults in Taipei City participated in this study. Data analyses included logistic and linear regression models. The 16-item and the short FES-I were strongly correlated (Spearman rho = 0.963), and both scales are reliable. The 7-item FES-I was positively associated with fall history and physical frailty and negatively associated with the physical (b = -0.65, p < 0.001) and mental (b = -0.59, p < 0.001) components of health-related quality of life, independent of physical frailty. Thus, the short FES-I can be used to increase the feasibility of health screenings of older adults in Chinese-speaking contexts.

USP19 modulates autophagy and antiviral immune responses by deubiquitinating Beclin-1.

Autophagy, mediated by a number of autophagy-related (ATG) proteins, plays an important role in the bulk degradation of cellular constituents. Beclin-1 (also known as Atg6 in yeast) is a core protein essential for autophagic initiation and other biological processes. The activity of Beclin-1 is tightly regulated by multiple post-translational modifications, including ubiquitination, yet the molecular mechanism underpinning its reversible deubiquitination remains poorly defined. Here, we identified ubiquitin-specific protease 19 (USP19) as a positive regulator of autophagy, but a negative regulator of type I interferon (IFN) signaling.USP19 stabilizes Beclin-1 by removing the K11-linked ubiquitin chains of Beclin-1 at lysine 437. Moreover, we foundthat USP19 negatively regulates type IIFNsignaling pathway, by blockingRIG-I-MAVSinteraction in a Beclin-1-dependent manner. Depletion of eitherUSP19 or Beclin-1 inhibits autophagic flux and promotes type IIFNsignaling as well as cellular antiviral immunity. Our findings reveal novel dual functions of theUSP19-Beclin-1 axis by balancing autophagy and the production of type IIFNs.

Alterations in Intestinal Innate Mucosal Immunity of Weaned Pigs During Porcine Epidemic Diarrhea Virus Infection.

In the small intestine, localized innate mucosal immunity is critical for intestinal homeostasis. Porcine epidemic diarrhea virus (PEDV) infection induces villus injury and impairs digestive function. Moreover, the infection might comprise localized innate mucosal immunity. This study investigated specific enterocyte subtypes and innate immune components of weaned pigs during PEDV infection. Four-week-old pigs were orally inoculated with PEDV IN19338 strain (n = 40) or sham-inoculated (n = 24). At day post inoculation (DPI) 2, 4, and 6, lysozyme expression in Paneth cells, cellular density of villous and Peyer's patch microfold (M) cells, and the expression of polymeric immunoglobulin receptor (pIgR) were assessed in the jejunum and ileum by immunohistochemistry, and interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were measured in the jejunum by ELISA. PEDV infection led to a decrease in the ratios of villus height to crypt depth (VH-CD) in jejunum at DPI 2, 4, and 6 and in ileum at DPI 4. The number of villous M cells was reduced in jejunum at DPI 4 and 6 and in ileum at DPI 6, while the number of Peyer's patch M cells in ileum increased at DPI 2 and then decreased at DPI 6. PEDV-infected pigs also had reduced lysozyme expression in ileal Paneth cells at DPI 2 and increased ileal pIgR expression at DPI 4. There were no significant changes in IL-1ß and TNF-α expression in PEDV-infected pigs compared to controls. In conclusion, PEDV infection affected innate mucosal immunity of weaned pigs through alterations in Paneth cells, villous and Peyer's patch M cells, and pIgR expression.