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Rootless plants in the genus Wolffia are some of the fastest growing known plants on Earth. Wolffia have a reduced body plan, primarily multiplying through a budding type of asexual reproduction. Here, we generated draft reference genomes for Wolffia australiana (Benth.) Hartog & Plas, which has the smallest genome size in the genus at 357 Mb and has a reduced set of predicted protein-coding genes at about 15,000. Comparison between multiple high-quality draft genome sequences from W. australiana clones confirmed loss of several hundred genes that are highly conserved among flowering plants, including genes involved in root developmental and light signaling pathways. Wolffia has also lost most of the conserved nucleotide-binding leucine-rich repeat (NLR) genes that are known to be involved in innate immunity, as well as those involved in terpene biosynthesis, while having a significant overrepresentation of genes in the sphingolipid pathways that may signify an alternative defense system. Diurnal expression analysis revealed that only 13% of Wolffia genes are expressed in a time-of-day (TOD) fashion, which is less than the typical ∼40% found in several model plants under the same condition. In contrast to the model plants Arabidopsis and rice, many of the pathways associated with multicellular and developmental processes are not under TOD control in W. australiana, where genes that cycle the conditions tested predominantly have carbon processing and chloroplast-related functions. The Wolffia genome and TOD expression data set thus provide insight into the interplay between a streamlined plant body plan and optimized growth.

Aging is characterized by a progressive loss of physiological integrity, while cancer represents one of the primary pathological factors that severely threaten human lifespan and healthspan. In clinical oncology, drug resistance limits the efficacy of most anticancer treatments, and identification of major mechanisms remains a key to solve this challenging issue. Here, we highlight the multifaceted senescence-associated secretory phenotype (SASP), which comprises numerous soluble factors including amphiregulin (AREG). Production of AREG is triggered by DNA damage to stromal cells, which passively enter senescence in the tumor microenvironment (TME), a process that remarkably enhances cancer malignancy including acquired resistance mediated by EGFR. Furthermore, paracrine AREG induces programmed cell death 1 ligand (PD-L1) expression in recipient cancer cells and creates an immunosuppressive TME via immune checkpoint activation against cytotoxic lymphocytes. Targeting AREG not only minimized chemoresistance of cancer cells, but also restored immunocompetency when combined with classical chemotherapy in humanized animals. Our study underscores the potential of in vivo SASP in driving the TME-mediated drug resistance and shaping an immunosuppressive niche, and provides the proof of principle of targeting major SASP factors to improve therapeutic outcome in cancer medicine, the success of which can substantially reduce aging-related morbidity and mortality.

Renal involvement in COVID-19 leads to severe disease and higher mortality. We study renal parameters in COVID-19 patients and their association with mortality and length of stay in hospital.

Background: LI‐RADS version 2018 (v2018) is used for non‐invasive diagnosis of hepatocellular carcinoma (HCC). A recently proposed modification (known as mLI‐RADS) demonstrated improved sensitivity while maintaining specificity and positive predictive value (PPV) of LI‐RADS category 5 (definite HCC) for HCC. However, mLI‐RADS requires multicenter validation. Purpose: To evaluate the performance of v2018 and mLI‐RADS for liver lesions in a large, heterogeneous, multi‐national cohort of patients at risk for HCC. Study Type: Systematic review and meta‐analysis using individual participant data (IPD) [Study Protocol: https://osf.io/duys4]. Population: 2223 observations from 1817 patients (includes all LI‐RADS categories; females = 448, males = 1361, not reported = 8) at elevated risk for developing HCC (based on LI‐RADS population criteria) from 12 retrospective studies. Field Strength/Sequence: 1.5T and 3T; complete liver MRI with gadoxetate disodium, including axial T2w images and dynamic axial fat‐suppressed T1w images precontrast and in the arterial, portal venous, transitional, and hepatobiliary phases. Diffusion‐weighted imaging was used when available. Assessment: Liver observations were categorized using v2018 and mLI‐RADS. The diagnostic performance of each system's category 5 (LR‐5 and mLR‐5) for HCC were compared. Statistical Tests: The Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS‐2 was applied to determine risk of bias and applicability. Diagnostic performances were assessed using the likelihood ratio test for sensitivity and specificity and the Wald test for PPV. The significance level was P < 0.05. Results: 17% (2/12) of the studies were considered low risk of bias (244 liver observations; 164 patients). When compared to v2018, mLR‐5 demonstrated higher sensitivity (61.3% vs. 46.5%, P < 0.001), similar PPV (85.3% vs. 86.3%, P = 0.89), and similar specificity (85.8% vs. 90.8%, P = 0.16) for HCC. Data Conclusion: This study confirms mLR‐5 has higher sensitivity than LR‐5 for HCC identification, while maintaining similar PPV and specificity, validating the mLI‐RADS proposal in a heterogeneous, international cohort. Level of Evidence: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

BACKGROUND: Inhaler education for patients with asthma and patients with COPD is typically provided by non-pulmonologists. We studied inhaler education by pulmonologists to determine changes in clinical outcomes and inhaler use. METHODS: This was a retrospective study of 296 subjects diagnosed with asthma, COPD, or both that evaluated use of inhaler technique education and its impact on (1) inhaler/dosage change consisting of dosage change in the same class of inhaler and/or change in number of inhalers, (2) forced expiratory volume in one second/forced vital capacity (FEV1/FVC%), (3) disease symptom control, (4) out-patient visits, (5) urgent care visits (6) emergency department visits, and (7) hospital admissions. One group received inhaler technique education by a pulmonologist while the other group did not. RESULTS: The pulmonologist inhaler technique--educated group had significantly decreased relative risk for inhaler/dosage increase (relative risk 0.57 [95% CI 0.34-0.96], P = .03) and significantly increased odds for symptom control (odds ratio 2.15 [95% CI 1.24-3.74], P = .01) at 1-y follow-up as compared to the no education group. No differences occurred for FEV1/FVC%, out-patient visits, urgent care visits, emergency department visits, and hospital admissions. CONCLUSIONS: Pulmonologist education of inhaler technique for patients with asthma and patients with COPD was associated with decreased relative risk for inhaler/dosage increase and increased odds for symptom control. We recommend pulmonologists provide education of inhaler technique to patients with asthma and patients with COPD and not rely on non-pulmonologist education alone. Prospective research is needed to confirm the importance of proper inhaler techniques. [ABSTRACT FROM AUTHOR]

Chemotherapy and radiation not only trigger cancer cell apoptosis but also damage stromal cells in the tumour microenvironment (TME), inducing a senescence-associated secretory phenotype (SASP) characterized by chronic secretion of diverse soluble factors. Here we report serine protease inhibitor Kazal type I (SPINK1), a SASP factor produced in human stromal cells after genotoxic treatment. DNA damage causes SPINK1 expression by engaging NF-κB and C/EBP, while paracrine SPINK1 promotes cancer cell aggressiveness particularly chemoresistance. Strikingly, SPINK1 reprograms the expression profile of cancer cells, causing prominent epithelial-endothelial transition (EET), a phenotypic switch mediated by EGFR signaling but hitherto rarely reported for a SASP factor. In vivo, SPINK1 is expressed in the stroma of solid tumours and is routinely detectable in peripheral blood of cancer patients after chemotherapy. Our study substantiates SPINK1 as both a targetable SASP factor and a novel noninvasive biomarker of therapeutically damaged TME for disease control and clinical surveillance.

The leading cause of death in cancer patients is metastasis, for which an effective treatment is still necessary. During metastasis, cancer cells aberrantly express several glycans that are correlated with poor patient outcome. This study was aimed toward exploring the effects of O-GlcNAcylation on membranous N-glycans that are associated with the progression of cholangiocarcinoma (CCA). Global O-GlcNAcylation in CCA cells was depleted using specific siRNA against O-GlcNAc transferase (OGT), which transfers GlcNAc to the acceptor proteins. Using an HPLC-Chip/Time-of-Flight (Chip/TOF) MS system, the N-glycans associated with O-GlcNAcylation were identified by comparing the membranous N-glycans of siOGT-treated cells with those of scramble siRNA-treated cells. In parallel, the membranous N-glycans of the parental cells (KKU-213 and KKU-214) were compared with those of the highly metastatic cells (KKU-213L5 and KKU-214L5). Together, these data revealed that high mannose (Hex9HexNAc2) and biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans correlated positively with metastasis. We subsequently demonstrate that suppression of O-GlcNAcylation decreased the expression of these two N-glycans, suggesting that O-GlcNAcylation mediates their levels in CCA. In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis. The molecular mechanism of O-GlcNAc-mediated progression of CCA was shown to proceed via a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv). This study demonstrates for the first time the association between O-GlcNAcylation, high mannose type N-glycans, and the progression of CCA metastasis, suggesting a novel therapeutic target for treatment of metastatic CCA.

Medical imaging diagnostic test accuracy research is strengthened by adhering to best practices for study design, data collection, data documentation, and study reporting. In this review, key elements of such research are discussed, and specific recommendations provided for optimizing diagnostic accuracy study execution to improve uniformity, minimize common sources of bias and avoid potential pitfalls. Examples are provided regarding study methodology and data collection practices based on insights gained by the liver imaging reporting and data system (LI‐RADS) individual participant data group, who have evaluated raw data from numerous MRI diagnostic accuracy studies for risk of bias and data integrity. The goal of this review is to outline strategies for investigators to improve research practices, and to help reviewers and readers better contextualize a study's findings while understanding its limitations. Level of Evidence: 5 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Club drug use—including 3,4-Methylenedioxymethamphetamine, ketamine, crack/cocaine, hallucinogens, gamma hydroxybutyrate, volatile nitrites, and methamphetamine—has been linked to sexual risk behaviors among MSM. Few studies examine how the use of club drugs and the association between club drug use during sex and sexual risk may differ by race/ethnicity. Using data from a cross-sectional study among alcohol-using MSM in San Francisco (n = 252), we examined the associations between the interaction of race/ethnicity and club drug use during sex, and the following behavioral outcomes: any condomless anal intercourse (CAI), insertive CAI, receptive CAI, and any serodiscordant sex in the past six months. All models controlled for income, HIV status, relationship status, age, and current use of a biomedical HIV prevention tool (i.e., Pre-Exposure Prophylaxis [PrEP] or antiretroviral therapy). There were significant racial differences in club drug use (p < 0.001) and club drug use during sex (p = 0.01). Asian/Pacific Islander (API) and Latino participants reported using club drugs the most at 78.8% and 79%, respectively. Among users of club drugs, club drug use during sex was most common among Black (100%), and Latino MSM (93%). Significant interactions between race/ethnicity and club drug use during sex were observed for CAI (p = 0.02), insertive CAI (p = 0.01), and receptive CAI (p = 0.01). API participants who used club drug during sex had higher odds of reporting CAI (aOR = 15.27, CI = 1.50–155.34), insertive CAI (aOR = 21.11, CI = 2.04–218.10), and receptive CAI (aOR = 21.11, CI = 2.04–218.10). Given the differing rates of club drug use during sex by race/ethnicity and the role race/ethnicity plays in modifying the relationships between club drug use during sex and sexual risk behaviors, culturally-tailored interventions may be needed to address the needs of ethnically-diverse, club drug-using MSM. [ABSTRACT FROM AUTHOR]