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ObjectiveThe adverse effects of proton pump inhibitors (PPIs) have been documented for pneumonia; however, there is no consensus regarding whether the use of PPIs might be harmful regarding the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this regard, we aimed to measure the potential associations of the current use of PPIs with the infection rates of COVID-19 among patients who underwent SARS-CoV-2 testing.DesignData were derived from a Korean nationwide cohort study with propensity score matching. We included 132 316 patients older than 18 years who tested for SARS-CoV-2 between 1 January and 15 May 2020. Endpoints were SARS-CoV-2 positivity (primary) and severe clinical outcomes of COVID-19 (secondary: admission to intensive care unit, administration of invasive ventilation or death).ResultsIn the entire cohort, there were 111 911 non-users, 14 163 current PPI users and 6242 past PPI users. After propensity score matching, the SARS-CoV-2 test positivity rate was not associated with the current or past use of PPIs. Among patients with confirmed COVID-19, the current use of PPIs conferred a 79% greater risk of severe clinical outcomes of COVID-19, while the relationship with the past use of PPIs remained insignificant. Current PPI use starting within the previous 30 days was associated with a 90% increased risk of severe clinical outcomes of COVID-19.ConclusionPatients taking PPIs are at increased risk for severe clinical outcomes of COVID-19 but not susceptible to SARS-CoV-2 infection. This suggests that physicians need to assess benefit–risk assessments in the management of acid-related diseases amid the COVID-19 pandemic.

PurposeTo determine the potential associations between physical activity and risk of SARS-CoV-2 infection, severe illness from COVID-19 and COVID-19 related death using a nationwide cohort from South Korea.MethodsData regarding 212 768 Korean adults (age ≥20 years), who tested for SARS-CoV-2, from 1 January 2020 to 30 May 2020, were obtained from the National Health Insurance Service of South Korea and further linked with the national general health examination from 1 January 2018 to 31 December 2019 to assess physical activity levels. SARS-CoV-2 positivity, severe COVID-19 illness and COVID-19 related death were the main outcomes. The observation period was between 1 January 2020 and 31 July 2020.ResultsOut of 76 395 participants who completed the general health examination and were tested for SARS-CoV-2, 2295 (3.0%) were positive for SARS-CoV-2, 446 (0.58%) had severe illness from COVID-19 and 45 (0.059%) died from COVID-19. Adults who engaged in both aerobic and muscle strengthening activities according to the 2018 physical activity guidelines had a lower risk of SARS-CoV-2 infection (2.6% vs 3.1%; adjusted relative risk (aRR), 0.85; 95% CI 0.72 to 0.96), severe COVID-19 illness (0.35% vs 0.66%; aRR 0.42; 95% CI 0.19 to 0.91) and COVID-19 related death (0.02% vs 0.08%; aRR 0.24; 95% CI 0.05 to 0.99) than those who engaged in insufficient aerobic and muscle strengthening activities. Furthermore, the recommended range of metabolic equivalent task (MET; 500–1000 MET min/week) was associated with the maximum beneficial effect size for reduced risk of SARS-CoV-2 infection (aRR 0.78; 95% CI 0.66 to 0.92), severe COVID-19 illness (aRR 0.62; 95% CI 0.43 to 0.90) and COVID-19 related death (aRR 0.17; 95% CI 0.07 to 0.98). Similar patterns of association were observed in different sensitivity analyses.ConclusionAdults who engaged in the recommended levels of physical activity were associated with a decreased likelihood of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related death. Our findings suggest that engaging in physical activity has substantial public health value and demonstrates potential benefits to combat COVID-19.

Background: Basic studies suggest that statins as add-on therapy may benefit patients with COVID-19; however, real-world evidence of such a beneficial association is lacking. Objective: We investigated differences in SARS-CoV-2 test positivity and clinical outcomes of COVID-19 (composite endpoint: admission to intensive care unit, invasive ventilation, or death) between statin users and nonusers. Methods: Two independent population-based cohorts were analyzed, and we investigated the differences in SARS-CoV-2 test positivity and severe clinical outcomes of COVID-19, such as admission to the intensive care unit, invasive ventilation, or death, between statin users and nonusers. One group comprised an unmatched cohort of 214,207 patients who underwent SARS-CoV-2 testing from the Global Research Collaboration Project (GRCP)-COVID cohort, and the other group comprised an unmatched cohort of 74,866 patients who underwent SARS-CoV-2 testing from the National Health Insurance Service (NHIS)-COVID cohort. Results: The GRCP-COVID cohort with propensity score matching had 29,701 statin users and 29,701 matched nonusers. The SARS-CoV-2 test positivity rate was not associated with statin use (statin users, 2.82% [837/29,701]; nonusers, 2.65% [787/29,701]; adjusted relative risk [aRR] 0.97; 95% CI 0.88-1.07). Among patients with confirmed COVID-19 in the GRCP-COVID cohort, 804 were statin users and 1573 were matched nonusers. Statin users were associated with a decreased likelihood of severe clinical outcomes (statin users, 3.98% [32/804]; nonusers, 5.40% [85/1573]; aRR 0.62; 95% CI 0.41-0.91) and length of hospital stay (statin users, 23.8 days; nonusers, 26.3 days; adjusted mean difference –2.87; 95% CI –5.68 to –0.93) than nonusers. The results of the NHIS-COVID cohort were similar to the primary results of the GRCP-COVID cohort. Conclusions: Our findings indicate that prior statin use is related to a decreased risk of worsening clinical outcomes of COVID-19 and length of hospital stay but not to that of SARS-CoV-2 infection.

The principal objective of the present study was to determine the positive effects of artificial illumination on the juvenile black rockfish Sebastes inermis by comparing stomach contents and growth between juveniles exposed to light and those maintained in the absence of light. The major prey items of juvenile black rockfish in illuminated cages were: copepods (%IRI = 62.6); amphipods (%IRI = 36.7); and polychaetes (%IRI = 0.3), whereas those in unilluminated cages were: copepods (%IRI = 93.3); amphipods (%IRI = 6.1); and polychaetes (%IRI = 0.4). The specific growth rates of the juveniles reared in illuminated cages (0.67%) were significantly higher than those juveniles maintained in the unilluminated cages (0.27%).

The aim of this study was to investigate the significance of serum prostate-specific antigen （PSA） value adjusted for total tumor volume （PSA/tumor volume） and serum PSA value adjusted for non-cancerous prostate tissue volume （NCPV） （PSA/NCPV） as a predictor of pathological findings and clinical outcome after radical prostatectomy. Clinical and pathological data of 407 patients （median age： 66.5 years; range： 41.8--85.7 years） were reviewed retrospectively. The median follow-up period was 18. I months （range： 1.0- 107.8 months）. Biochemical recurrence was defined as detectable PSA levels （greater than 0.2 ng ml-1） and the time of biochemical recurrence was taken to be the first time PSA became detectable. In the multivariate model, PSA/NCPV was an independent predictor of extracapsular extension and positive surgical margin （P〈O.05）, but PSA/tumor volume was not. Kaplan-Meier curves revealed that PSA/NCPV correlated with biochemical recurrence-free survival （P〈O.O01; log-rank test） but PSA/tumor volume did not （P=0.275; log-rank test）. PSA/NCPV was also a significant independent prognostic factor for biochemical recurrence-free survival on multivariate Cox proportional hazard analysis （P=0.004, relative risk=2.42）. Our findings suggest that PSA/NCPV is associated independently with extracapsular extension and surgical margin status and may be an independent prognostic variable of PSA recurrence after radical prostatectomy.

We herein investigated the role of the STAT signaling cascade in the production of pro-inflammatory cytokines and cisplatin ototoxicity. A significant hearing impairment caused by cisplatin injection was observed in Balb/c （wild type, WT） and STAT4-/-, but not in STAT6-/- mice. Moreover, the expression levels of the protein and mRNA of pro- inflammatory cytokines, including TNF-u, IL-Ⅱ, and IL-6, were markedly increased in the serum and cochlea of WT and STAT4-/-, but not STAT6-/- mice. Organotypic culture revealed that the shape of stereocilia bundles and arrays of sensory hair cell layers in the organ of Corti from STAT6-j- mice were intact after treatment with cisplatin, where- as those from WT and STAT4-/- mice were highly distorted and disarrayed after the treatment. Cisplatin induced the phosphorylation of STAT6 in HEI-OC1 auditory ceils, and the knockdown of STAT6 by STAT6-specific siRNA significantly protected HEI-OC1 auditory cells from cisplatin-induced cell death and inhibited pro-inflammatory cytokine production. We further demonstrated that IL-4 and IL-13 induced by cisplatin modulated the phosphoryla- tion of STAT6 by binding with IL-4 receptor alpha and IL-13Rul. These findings suggest that STAT6 signaling plays a pivotal role in cisplatin-mediated pro-inflammatory cytokine production and ototoxicity.

We develop a quantum key distribution （QKD） system with fast active optical path length compensation. A rapid and reliable active optical path length compensation scheme is proposed and applied to a plug-and-play QKD system. The system monitors changes in key rates and controls it is own operation automatically. The system achieves its optimal performance within three seconds of operation, which includes a sifted key rate of 5.5 kbps and a quantum bit error rate of less than 2% after an abrupt temperature variation along the 25 km quantum channel. The system also operates well over a 24 h period while completing more than 60 active optical path length compensations.

Somatic cells can be reprogrammed into induced pluripotent stem （iPS） cells by the transcription factors Oct4, Sox2, and Kif4 in combination with c-Myc. Recently, Sox2 plus Oct4 was shown to reprogram fibroblasts and Oct4 alone was able to reprogram mouse and human neural stem cells （NSCs） into iPS cells. Here, we report that Bmil leads to the transdifferentiation of mouse fibroblasts into NSC-Iikc cells, and, in combination with Oct4, can replace Sox2, Klf4 and c-Myc during the reprogramming of fibroblasts into iPS cells. Furthermore, activation of sonic hedgehog signaling （by Shh, purmorphamine, or oxysterol） compensates for the effects of Bmil, and, in combination with Oct4, reprograms mouse embryonic and adult fibroblasts into iPS cells. One- and two-factor iPS cells are similar to mouse embryonic stem cells in their global gene expression profile, epigenetic status, and in vitro and in vivo differentiation into all three germ layers, as well as teratoma formation and germline transmission in vivo. These data support that converting fibroblasts with Broil or activation of the sonic hedgehog pathway to an intermediate cell type that expresses Sox2, Klf4, and N-Myc allows iPS generation via the addition of Oct4.

T cell‐derived small extracellular vesicles (sEVs) exhibit anti‐cancer effects. However, their anti‐cancer potential should be reinforced to enhance clinical applicability. Herein, we generated interleukin‐2‐tethered sEVs (IL2‐sEVs) from engineered Jurkat T cells expressing IL2 at the plasma membrane via a flexible linker to induce an autocrine effect. IL2‐sEVs increased the anti‐cancer ability of CD8+ T cells without affecting regulatory T (Treg) cells and down‐regulated cellular and exosomal PD‐L1 expression in melanoma cells, causing their increased sensitivity to CD8+ T cell‐mediated cytotoxicity. Its effect on CD8+ T and melanoma cells was mediated by several IL2‐sEV‐resident microRNAs (miRNAs), whose expressions were upregulated by the autocrine effects of IL2. Among the miRNAs, miR‐181a‐3p and miR‐223‐3p notably reduced the PD‐L1 protein levels in melanoma cells. Interestingly, miR‐181a‐3p increased the activity of CD8+ T cells while suppressing Treg cell activity. IL2‐sEVs inhibited tumour progression in melanoma‐bearing immunocompetent mice, but not in immunodeficient mice. The combination of IL2‐sEVs and existing anti‐cancer drugs significantly improved anti‐cancer efficacy by decreasing PD‐L1 expression in vivo. Thus, IL2‐sEVs are potential cancer immunotherapeutic agents that regulate both immune and cancer cells by reprogramming miRNA levels.