Efficacy of topical treatments for mild-to-moderate acne: A systematic review and meta-analysis of randomized control trials.

Acne is a common skin condition, but little data exist on the comparative efficacy of topical acne therapies. We conducted a systematic review and network meta-analysis to evaluate the efficacy of topical therapies for mild-to-moderate acne. Searches in PubMed/MEDLINE, Cochrane CENTRAL via Ovid, Embase via Ovid and Web of Science were conducted on 29 November 2021. Randomized controlled trials examining ≥12 weeks of topical treatments for acne vulgaris in subjects aged 12 and older were included. Main outcomes were absolute or percent change in acne lesion count and treatment success on the Investigator's Global Assessment scale. Thirty-five randomized clinical trials with 33,472 participants comparing nine different topical agents were included. Adapalene-benzoyl peroxide (BPO), clindamycin-BPO and clindamycin-tretinoin demonstrated the greatest reduction in non-inflammatory (ratio of means [RoM] 1.76; 95% CI [1.46; 2.12], RoM 1.70; 95% CI [1.44; 2.02] and RoM 1.87; 95% CI [1.53; 2.30], respectively), inflammatory (RoM 1.56; 95% CI [1.44; 1.70], RoM 1.49; 95% CI [1.39; 1.60] and RoM 1.48; 95% CI [1.36; 1.61], respectively) and total lesion count (ROM 1.67; 95% CI [1.47; 1.90], RoM 1.59; 95% CI [1.42; 1.79] and RoM 1.64; 95% CI [1.42; 1.89], respectively) compared to placebo. All single agents outperformed placebo except tazarotene, which did not significantly outperform placebo for inflammatory and non-inflammatory lesion count reduction. Most combination agents significantly outperformed their individual components in lesion count reduction and global assessment scores, except for clindamycin-tretinoin and clindamycin-BPO, which did not significantly outperform tretinoin (RoM 1.13; 95% CI [0.94; 1.36]) and BPO (RoM = 1.15, 95% CI [0.98; 1.36]), respectively, for non-inflammatory lesion reduction. There was no significant difference amongst most single agents when evaluating lesion count reduction. Combination agents are generally most effective for mild-to-moderate acne; however for non-inflammatory acne, the addition of clindamycin in topical regimens is unnecessary and should be avoided.

Identification and Regulation of Hypoxia-Tolerant and Germination-Related Genes in Rice.

In direct seeding, hypoxia is a major stress faced by rice plants. Therefore, dissecting the response mechanism of rice to hypoxia stress and the molecular regulatory network is critical to the development of hypoxia-tolerant rice varieties and direct seeding of rice. This review summarizes the morphological, physiological, and ecological changes in rice under hypoxia stress, the discovery of hypoxia-tolerant and germination-related genes/QTLs, and the latest research on candidate genes, and explores the linkage of hypoxia tolerance genes and their distribution in indica and japonica rice through population variance analysis and haplotype network analysis. Among the candidate genes, OsMAP1 is a typical gene located on the MAPK cascade reaction for indica-japonica divergence; MHZ6 is involved in both the MAPK signaling and phytohormone transduction pathway. MHZ6 has three major haplotypes and one rare haplotype, with Hap3 being dominated by indica rice varieties, and promotes internode elongation in deep-water rice by activating the SD1 gene. OsAmy3D and Adh1 have similar indica-japonica varietal differentiation, and are mainly present in indica varieties. There are three high-frequency haplotypes of OsTPP7, namely Hap1 (n = 1109), Hap2 (n = 1349), and Hap3 (n = 217); Hap2 is more frequent in japonica, and the genetic background of OsTPP7 was derived from the japonica rice subpopulation. Further artificial selection, natural domestication, and other means to identify more resistance mechanisms of this gene may facilitate future research to breed superior rice cultivars. Finally, this study discusses the application of rice hypoxia-tolerant germplasm in future breeding research.

Single-cell analysis of localized prostate cancer patients links high Gleason score with an immunosuppressive profile.

BACKGROUND: Evading immune surveillance is a hallmark for the development of multiple cancer types. Whether immune evasion contributes to the pathogenesis of high-grade prostate cancer (HGPCa) remains an area of active inquiry. METHODS: Through single-cell RNA sequencing and multicolor flow cytometry of freshly isolated prostatectomy specimens and matched peripheral blood, we aimed to characterize the tumor immune microenvironment (TME) of localized prostate cancer (PCa), including HGPCa and low-grade prostate cancer (LGPCa). RESULTS: HGPCa are highly infiltrated by exhausted CD8+ T cells, myeloid cells, and regulatory T cells (TRegs). These HGPCa-infiltrating CD8+ T cells expressed high levels of exhaustion markers including TIM3, TOX, TCF7, PD-1, CTLA4, TIGIT, and CXCL13. By contrast, a high ratio of activated CD8+  effector T cells relative to TRegs and myeloid cells infiltrate the TME of LGPCa. HGPCa CD8+  tumor-infiltrating lymphocytes (TILs) expressed more androgen receptor and prostate-specific membran antigen yet less prostate-specific antigen than the LGPCa CD8+  TILs. The PCa TME was infiltrated by macrophages but these did not clearly cluster by M1 and M2 markers. CONCLUSIONS: Our study reveals a suppressive TME with high levels of CD8+ T cell exhaustion in localized PCa, a finding enriched in HGPCa relative to LGPCa. These studies suggest a possible link between the clinical-pathologic risk of PCa and the associated TME. Our results have implications for our understanding of the immunologic mechanisms of PCa pathogenesis and the implementation of immunotherapy for localized PCa.

Risk and tropism of central nervous system (CNS) metastases in patients with stage II and III cutaneous melanoma.

BACKGROUND: Recent data suggest that patients with stage III melanoma are at high risk for developing central nervous system (CNS) metastases. Because a subset of patients with stage II melanoma experiences worse survival outcomes than some patients with stage III disease, the authors investigated the risk of CNS metastasis in stage II melanoma to inform surveillance guidelines for this population. METHODS: The authors examined clinicopathologic data prospectively collected from 1054 patients who had cutaneous melanoma. The χ2 test, the cumulative incidence, and Cox multivariable regression analyses were performed to evaluate the association between baseline characteristics and the development of CNS metastases. RESULTS: Patients with stage III melanoma had a higher rate of developing brain metastases than those with stage II melanoma (100 of 468 patients [21.4%] vs. 82 of 586 patients [14.0%], respectively; p = .002). However, patients who had stage IIC melanoma had a significantly higher rate of isolated first recurrences in the CNS compared with those who had stage III disease (12.1% vs. 3.6%; p = .002). The risk of ever developing brain metastases was similarly elevated for patients who had stage IIC disease (hazard ratio [HR], 3.16; 95% CI, 1.77-5.66), stage IIIB disease (HR, 2.83; 95% CI, 1.63-4.91), and stage IIIC disease (HR, 2.93; 95% CI, 1.81-4.74), and the risk was highest in patients who had stage IIID disease (HR, 8.59; 95% CI: 4.11-17.97). CONCLUSIONS: Patients with stage IIC melanoma are at elevated risk for first recurrence in the CNS. Surveillance strategies that incorporate serial neuroimaging should be considered for these individuals until more accurate predictive markers can be identified.

mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized, Double-Blind, Placebo-Controlled Futility Trial and 1-Year Biomarker Longitudinal Analysis.

BACKGROUND: Multiple system atrophy (MSA) is a fatal neurodegenerative disease characterized by the aggregation of α-synuclein in glia and neurons. Sirolimus (rapamycin) is an mTOR inhibitor that promotes α-synuclein autophagy and reduces its associated neurotoxicity in preclinical models. OBJECTIVE: To investigate the efficacy and safety of sirolimus in patients with MSA using a futility design. We also analyzed 1-year biomarker trajectories in the trial participants. METHODS: Randomized, double-blind, parallel group, placebo-controlled clinical trial at the New York University of patients with probable MSA randomly assigned (3:1) to sirolimus (2-6 mg daily) for 48 weeks or placebo. Primary endpoint was change in the Unified MSA Rating Scale (UMSARS) total score from baseline to 48 weeks. (ClinicalTrials.gov NCT03589976). RESULTS: The trial was stopped after a pre-planned interim analysis met futility criteria. Between August 15, 2018 and November 15, 2020, 54 participants were screened, and 47 enrolled and randomly assigned (35 sirolimus, 12 placebo). Of those randomized, 34 were included in the intention-to-treat analysis. There was no difference in change from baseline to week 48 between the sirolimus and placebo in UMSARS total score (mean difference, 2.66; 95% CI, -7.35-6.91; P = 0.648). There was no difference in UMSARS-1 and UMSARS-2 scores either. UMSARS scores changes were similar to those reported in natural history studies. Neuroimaging and blood biomarker results were similar in the sirolimus and placebo groups. Adverse events were more frequent with sirolimus. Analysis of 1-year biomarker trajectories in all participants showed that increases in blood neurofilament light chain (NfL) and reductions in whole brain volume correlated best with UMSARS progression. CONCLUSIONS: Sirolimus for 48 weeks was futile to slow the progression of MSA and had no effect on biomarkers compared to placebo. One-year change in blood NfL and whole brain atrophy are promising biomarkers of disease progression for future clinical trials. © 2022 International Parkinson and Movement Disorder Society.

Treatment with therapeutic anticoagulation is not associated with immunotherapy response in advanced cancer patients.

BACKGROUND: Recent preclinical data suggest that there may be therapeutic synergy between immune checkpoint blockade and inhibition of the coagulation cascade. Here, we investigate whether patients who received immune checkpoint inhibitors (ICI) and were on concomitant anticoagulation (AC) experienced better treatment outcomes than individuals not on AC.Affiliation: Kindly confirm if corresponding authors affiliation is identified correctly.The corresponding author's affiliation is correct. METHODS: We studied a cohort of 728 advanced cancer patients who received 948 lines of ICI at NYU (2010-2020). Patients were classified based on whether they did (n = 120) or did not (n = 828) receive therapeutic AC at any point during their treatment with ICI. We investigated the relationship between AC status and multiple clinical endpoints including best overall response (BOR), objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and the incidence of bleeding complications.Affiliations: Journal instruction requires a country for affiliations; however, this is missing in affiliations 1 to 5. Please verify if the provided country is correct and amend if necessary.The country is correct for all affiliations (1 - 5). RESULTS: Treatment with AC was not associated with significantly different BOR (P = 0.80), ORR (P =0.60), DCR (P =0.77), PFS (P = 0.59), or OS (P =0.64). Patients who received AC were significantly more likely to suffer a major or clinically relevant minor bleed (P = 0.05). CONCLUSION: AC does not appear to impact the activity or efficacy of ICI in advanced cancer patients. On the basis of our findings, we caution that there is insufficient evidence to support prospectively evaluating the combination of AC and immunotherapy.

The ongoing racial disparities in melanoma: An analysis of the Surveillance, Epidemiology, and End Results database (1975-2016).

BACKGROUND: Although most patients with cutaneous melanoma are non-Hispanic whites (NHWs), minorities consistently suffer worse melanoma-specific survival (MSS). Much of the literature comes from analyses of registries from the 1990s and 2000s. OBJECTIVE: We sought to evaluate whether and to what degree racial disparity in MSS persists since 2010. METHODS: We analyzed 381,035 patients from the Surveillance, Epidemiology, and End Results registry. Race categories included Hispanic, NHW, non-Hispanic black (NHB), non-Hispanic Asian or Pacific Islander (NHAPI), and non-Hispanic American Indian/Alaska Native (NHAIAN). We evaluated the association between MSS and race in 3 time periods: before the year 2000, 2000 to 2009, and 2010 or later. NHW was the reference group for all analyses. RESULTS: Racial disparity worsened from before the year 2000 to 2010 or later for Hispanic (P < .001), NHB (P = .024), and NHAPI (P < .001) patients. Across all minority groups, patients with localized disease suffered increasing disparity (P = .010 for Hispanic, P < .001 for NHB, P = .023 for NHAPI, and P = .042 for NHAIAN patients). Among those with regional and distant disease, Hispanic patients were the only minority to experience worsening disparity (P = .001 and P = .019, respectively). LIMITATIONS: Lack of immunotherapy and targeted treatment information. CONCLUSIONS: Racial disparity in MSS is worsening. Improving postdiagnosis management for minorities with localized disease is imperative to mitigate disparity and improve survival.

A Role for Sensory end Organ-Derived Signals in Regulating Muscle Spindle Proprioceptor Phenotype.

Proprioceptive feedback from Group Ia/II muscle spindle afferents and Group Ib Golgi tendon afferents is critical for the normal execution of most motor tasks, yet how these distinct proprioceptor subtypes emerge during development remains poorly understood. Using molecular genetic approaches in mice of either sex, we identified 24 transcripts that have not previously been associated with a proprioceptor identity. Combinatorial expression analyses of these markers reveal at least three molecularly distinct proprioceptor subtypes. In addition, we find that 12 of these transcripts are expressed well after proprioceptors innervate their respective sensory receptors, and expression of three of these markers, including the heart development molecule Heg1, is significantly reduced in mice that lack muscle spindles. These data reveal Heg1 as a putative marker for proprioceptive muscle spindle afferents. Moreover, they suggest that the phenotypic specialization of functionally distinct proprioceptor subtypes depends, in part, on extrinsic sensory receptor organ-derived signals.SIGNIFICANCE STATEMENT Sensory feedback from muscle spindle (MS) and Golgi tendon organ (GTO) sensory end organs is critical for normal motor control, but how distinct MS and GTO afferent sensory neurons emerge during development remains poorly understood. Using (bulk) transcriptome analysis of genetically identified proprioceptors, this work reveals molecular markers for distinct proprioceptor subsets, including some that appear selectively expressed in MS afferents. Detailed analysis of the expression of these transcripts provides evidence that MS/GTO afferent subtype phenotypes may, at least in part, emerge through extrinsic, sensory end organ-derived signals.

Revisiting the association between skin toxicity and better response in advanced cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibition (ICI) improves survival outcomes for patients with several types of cancer including metastatic melanoma (MM), but serious immune-related adverse events requiring intervention with immunosuppressive medications occur in a subset of patients. Skin toxicity (ST) has been reported to be associated with better response to ICI. However, understudied factors, such as ST severity and potential survivor bias, may influence the strength of these observed associations. METHODS: To examine the potential confounding impact of such variables, we analyzed advanced cancer patients enrolled prospectively in a clinicopathological database with protocol-driven follow up and treated with ICI. We tested the associations between developing ST, stratified as no (n = 617), mild (n = 191), and severe (n = 63), and progression-free survival (PFS) and overall survival (OS) in univariable and multivariable analyses. We defined severe ST as a skin event that required treatment with systemic corticosteroids. To account for the possibility of longer survival associating with adverse events instead of the reverse, we treated ST as a time-dependent covariate in an adjusted model. RESULTS: Both mild and severe ST were significantly associated with improved PFS and OS (all P < 0.001). However, when adjusting for the time from treatment initiation to time of skin event, severe ST was not associated with PFS benefit both in univariable and multivariable analyses (P = 0.729 and P = 0.711, respectively). Receiving systemic steroids for ST did not lead to significant differences in PFS or OS compared to patients who did not receive systemic steroids. CONCLUSIONS: Our data reveal the influence of time to event and its severity as covariates in analyzing the relationship between ST and ICI outcomes. These differences in outcomes cannot be solely explained by the use of immunosuppressive medications, and thus highlight the importance of host- and disease-intrinsic factors in determining ICI response and toxicity. TRIAL REGISTRATION: The patient data used in this manuscript come from patients who were prospectively enrolled in two institutional review board-approved databases at NYU Langone Health (institutional review board #10362 and #S16-00122).

Outcomes of the Treatment with Glecaprevir/Pibrentasvir following heart transplantation utilizing hepatitis C viremic donors.

BACKGROUND: The use of direct-acting antivirals (DAA) has expanded transplantation from hepatitis C viremic donors (HCV-VIR). Our team has conducted an open-label, prospective trial to assess outcomes transplanting HCV viremic hearts. Glecaprevir/pibrentasvir (GLE/PIB) was our sole DAA. METHODS: Serial quantitative hepatitis C virus (HCV) RNA PCR was obtained to assess HCV viral titers. Between January 2018 and June 2019, a total of 50 recipients were transplanted. Of these, 22/50 (44%) were from HCV-VIR, the remaining 28 from non-viremic (HCV NON-VIR) donors. An 8-week course of GLE/PIB was initiated at 1 week post-transplant. RESULTS: There was no difference in demographic or clinical parameters between groups. All 22 recipients of HCV-VIR transplants became viremic. GLE/PIB was effective in decreasing viremia to undetectable levels by 6 weeks post-transplant in all patients. The median time to first undetectable HCV quantitative PCR was (4.3 weeks, IQR: 4-5.7 weeks). All patients demonstrated sustained undetectable viral load through 1-year follow-up. There was no difference in survival at one year between HCV NON-VIR 28/28: (100%) vs HCV-VIR 21/22 (95%) recipients. CONCLUSIONS: Our center reports excellent outcomes in transplanting utilizing hearts from HCV-VIR donors. No effect on survival or co-morbidity was found. An 8-week GLE/PIB course was safe and effective when initiated approximately 1 week post-transplant.

Demographics Predict Stage III/IV Colorectal Cancer in Individuals Under Age 50.

GOALS: The goal of this study was to quantify the association between demographic factors and advanced colorectal cancer (CRC) in patients under age 50. BACKGROUND: CRC incidence in the United States has declined in older individuals but increased in those under age 50 (early-onset). More than 60% of early-onset CRC patients present with advanced disease (stage III/IV), but predictors of stage in this population are poorly defined. STUDY: We analyzed CRC cases diagnosed between age 20 and 49 in the United States Surveillance, Epidemiology, and End Results (SEER) 18 database during 2004 to 2015. Logistic regression models were fit to assess the impact of age, sex, race, ethnicity, marital status, and cancer site on the probability of advanced disease. RESULTS: The analysis included 37,044 cases. On multivariable regression, age was inversely associated with advanced disease. Relative to 45 to 49-year-olds, 40 to 44-year-olds had 8% greater odds of having advanced CRC, and 20 to 24-year-olds had 53% greater odds. Asians, blacks, and Pacific Islanders had 10%, 12%, and 45% greater odds of advanced disease compared with whites. Compared with nonpartnered individuals, those with partners had 11% lower odds of advanced CRC. Both right-sided and left-sided colon cancer were more likely to be diagnosed at stage IV compared with rectal cancer. CONCLUSIONS: Among individuals with early-onset CRC, younger age, Asian, black, or Pacific Islander race, and being nonpartnered were predictors of advanced disease at presentation. Colon cancer was more likely to be diagnosed at stage IV than rectal cancer. Patient characteristics associated with advanced CRC may indicate both differences in tumor biology and disparities in health care access.

CLIP Tool Kit (CTK): a flexible and robust pipeline to analyze CLIP sequencing data.

Summary: UV cross-linking and immunoprecipitation (CLIP), followed by high-throughput sequencing, is a powerful biochemical assay that maps in vivo protein-RNA interactions on a genome-wide scale. The CLIP Tool Kit (CTK) aims at providing a set of tools for flexible, streamlined and comprehensive CLIP data analysis. This software package extends the scope of our original CIMS package. Availability and Implementation: The software is implemented in Perl. The source code and detailed documentation are available at http://zhanglab.c2b2.columbia.edu/index.php/CTK . Contact: cz2294@columbia.edu.

Immune biomarkers are more accurate in prediction of survival in ulcerated than in non-ulcerated primary melanomas.

INTRODUCTION: Ulcerated melanomas may have a unique biology and microenvironment. We test whether markers of immune infiltration correlate with clinical outcome in ulcerated compared to non-ulcerated primary melanoma tumors. METHODS: Sixty-two stage II-III cutaneous melanomas, 32 ulcerated and 30 non-ulcerated, were analyzed for tumor-infiltrating lymphocytes (TILs). Immunohistochemistry (IHC) was performed for CD2, a marker previously shown to correlate with overall survival (OS) and recurrence-free survival (RFS) in this patient population. IHC using antibody, VE1, to BRAF V600E was also performed on a subset of 41 tumors to assess the relationship of BRAF mutation to immune markers. RESULTS: We found, using Cox regression models, that the presence of TILs was associated with improved OS (p = 0.034) and RFS (p = 0.002) in ulcerated melanoma tumors, but not in non-ulcerated melanoma (p = 0.632, 0.416). CD2 expression also was correlated with improved OS (p = 0.021) and RFS (p = 0.001) in ulcerated melanoma, but no relationship was seen in non-ulcerated melanoma (p = 0.427, 0.682). In this small population, BRAF status did not correlate with TILs or CD2+ count. CONCLUSION: Our data show that immune markers including TILs and CD2 count correlate more closely with survival in ulcerated melanomas than that in non-ulcerated melanomas. We propose that immune biomarkers may be particularly relevant to ulcerated, as compared to non-ulcerated, melanomas and that this merits study in larger populations.

Gastric Cancer Risk Factors in a Veteran Population.

INTRODUCTION: Risk factors for gastric cancer in the United States are not well understood, especially in populations with a low proportion of immigrants. We conducted a matched case-control study in a Veteran Affairs Medical Center to identify risk factors for gastric cancer. MATERIALS AND METHODS: Gastric cancer patients and age- and sex-matched controls were identified in a 1:4 ratio from January 1, 1997 to October 31, 2018. Demographic, medical, endoscopic, and histologic data were extracted. We performed conditional logistic regression to estimate odds ratios and 95% CIs for associations between potential risk factors and gastric cancer. RESULTS: Most gastric cancer cases were diagnosed on initial endoscopy (71.4%). Of these, the most common presenting stage was stage IV (40.8%). Risk factors for gastric cancer included Black and Asian race and never or current (compared to former) drinkers, although Helicobacter pylori eradication and pernicious anemia were associated with decreased risk. CONCLUSIONS: The high proportion of late-stage gastric cancer diagnoses highlights the need for improved risk stratification as well as screening and surveillance protocols in the U.S. population. Racial disparities among veterans in an equal-access system necessitate further investigation into the etiology of these disparities.

Incidence, Complications, and Long-term Outcomes of Gender-affirming Phalloplasty: Analysis of a Large Statewide Population-based Dataset.

OBJECTIVE: To evaluate the incidence of gender-affirming phalloplasty and postoperative complications in a large population-based dataset. METHODS: Retrospective cohort study was done using the California Department of Health Care Access and Information datasets which include patient-level data from all licensed hospitals, emergency departments, and ambulatory surgery facilities in California. Adult patients 18 years or older undergoing gender-affirming phalloplasty in California from January 1, 2009 to December 31, 2019 were included. We examined phalloplasty-related complications using International Classification of Disease diagnosis and procedure codes and Current Procedural Terminology codes. Unique record linkage number identifiers were used to follow patients longitudinally. Statistical analysis included Kaplan-Meier survival analysis and Cox proportional hazards analysis. RESULTS: We identified 766 patients who underwent gender-affirming phalloplasty in 23 facilities. Of 475 patients with record linkage numbers, 253 (55.3%) had subsequent re-presentations to the inpatient, emergency department, and ambulatory surgery settings related to phalloplasty complications. Survival analysis indicated that 50% of patients re-presented by 1year post-phalloplasty. Asian/Pacific Islander patients had lower risk of complications, and California residents had higher risk of complications. CONCLUSION: This population-based study confirms that gender-affirming phalloplasty has a high complication rate, and demonstrates for the first time an association with high rates of return to hospitals, emergency departments, and ambulatory surgery centers. These findings provide additional higher-level evidence that may aid patient counseling, shared surgical decision-making, and institutional and government policy.

Functional differentiation and genetic diversity of rice cation exchanger (CAX) genes and their potential use in rice improvement.

Cation exchanger (CAX) genes play an important role in plant growth/development and response to biotic and abiotic stresses. Here, we tried to obtain important information on the functionalities and phenotypic effects of CAX gene family by systematic analyses of their expression patterns, genetic diversity (gene CDS haplotypes, structural variations, gene presence/absence variations) in 3010 rice genomes and nine parents of 496 Huanghuazhan introgression lines, the frequency shifts of the predominant gcHaps at these loci to artificial selection during modern breeding, and their association with tolerances to several abiotic stresses. Significant amounts of variation also exist in the cis-regulatory elements (CREs) of the OsCAX gene promoters in 50 high-quality rice genomes. The functional differentiation of OsCAX gene family were reflected primarily by their tissue and development specific expression patterns and in varied responses to different treatments, by unique sets of CREs in their promoters and their associations with specific agronomic traits/abiotic stress tolerances. Our results indicated that OsCAX1a and OsCAX2 as general signal transporters were in many processes of rice growth/development and responses to diverse environments, but they might be of less value in rice improvement. OsCAX1b, OsCAX1c, OsCAX3 and OsCAX4 was expected to be of potential value in rice improvement because of their associations with specific traits, responsiveness to specific abiotic stresses or phytohormones, and relatively high gcHap and CRE diversity. Our strategy was demonstrated to be highly efficient to obtain important genetic information on genes/alleles of specific gene family and can be used to systematically characterize the other rice gene families.

Genome-Wide Association Study of Xian Rice Grain Shape and Weight in Different Environments.

Drought is one of the key environmental factors affecting the growth and yield potential of rice. Grain shape, on the other hand, is an important factor determining the appearance, quality, and yield of rice grains. Here, we re-sequenced 275 Xian accessions and then conducted a genome-wide association study (GWAS) on six agronomic traits with the 404,411 single nucleotide polymorphisms (SNPs) derived by the best linear unbiased prediction (BLUP) for each trait. Under two years of drought stress (DS) and normal water (NW) treatments, a total of 16 QTLs associated with rice grain shape and grain weight were detected on chromosomes 1, 2, 3, 4, 5, 7, 8, 11, and 12. In addition, these QTLs were analyzed by haplotype analysis and functional annotation, and one clone (GSN1) and five new candidate genes were identified in the candidate interval. The findings provide important genetic information for the molecular improvement of grain shape and weight in rice.

Genome-Wide Association Study of Rice Grain Shape and Chalkiness in a Worldwide Collection of Xian Accessions.

Rice (Oryza sativa L.) appearance quality, which is mainly defined by grain shape and chalkiness, is an important target in rice breeding. In this study, we first re-sequenced 137 indica accessions and then conducted a genome-wide association study (GWAS) for six agronomic traits with the 2,998,034 derived single nucleotide polymorphisms (SNPs) by using the best linear unbiased prediction (BLUP) values for each trait. The results revealed that 195 SNPs had significant associations with the six agronomic traits. Based on the genome-wide linkage disequilibrium (LD) blocks, candidate genes for the target traits were detected within 100 kb upstream and downstream of the relevant SNP loci. Results indicate that six quantitative trait loci (QTLs) significantly associated with six traits (qTGW4.1, qTGW4.2, qGL4.1, qGL12.1, qGL12.2, qGW2.1, qGW4.1, qGW6.1, qGW8.1, qGW8.2, qGW9.1, qGW11.1, qGLWR2.1, qGLWR2.2, qGLWR4.2, qPGWC5.1 and qDEC6.1) were identified for haplotype analysis. Among these QTLs, two (qTGW4.2 and qGW6.1), were overlapped with FLO19 and OsbZIP47, respectively, and the remaining four were novel QTLs. These candidate genes were further validated by haplotype block construction.

Geriatric Conditions Among Middle-aged and Older Adults on Methadone Maintenance Treatment: A Pilot Study.

OBJECTIVES: The number of older adults on methadone maintenance treatment (MMT) for opioid use disorder is increasing, but little is known about the characteristics and healthcare needs of this aging treatment population. This population may experience accelerated aging due to comorbidities and health behaviors. The aim of this study was to compare the prevalence of geriatric conditions among adults age ≥50 on MMT to a nationally representative sample of community-dwelling older adults. METHODS: We performed a geriatric assessment on 47 adults age ≥50 currently on MMT enrolled in 2 opioid treatment programs, in New York City and in East Providence, Rhode Island. We collected data on self-reported geriatric conditions, healthcare utilization, chronic medical conditions, physical function, and substance use. The results were compared to 470 age, sex, and race/ethnicity-matched adults in the national Health and Retirement Study. RESULTS: The mean age of the study sample was 58.8 years and 23.4% were female. The most common chronic diseases were hypertension (59.6%) and arthritis (55.3%) with 66% reporting ≥2 diseases. For geriatric conditions, adults on MMT had a significantly higher prevalence of mobility, hearing, and visual impairments as well as falls, urinary incontinence, chronic pain, and insomnia than the Health and Retirement Study sample. CONCLUSIONS: Older adults on MMT in 2 large opioid treatment programs have a high prevalence of geriatric conditions. An interdisciplinary, geriatric-based approach to care that focuses on function and addresses geriatric conditions is needed to improve the health of this growing population.

Utilization of Palliative Care for Patients with COVID-19 and Acute Kidney Injury during a COVID-19 Surge.

BACKGROUND AND OBJECTIVES: AKI is a common complication of coronavirus disease 2019 (COVID-19) and is associated with high mortality. Palliative care, a specialty that supports patients with serious illness, is valuable for these patients but is historically underutilized in AKI. The objectives of this paper are to describe the use of palliative care in patients with AKI and COVID-19 and their subsequent health care utilization. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective analysis of New York University Langone Health electronic health data of COVID-19 hospitalizations between March 2, 2020 and August 25, 2020. Regression models were used to examine characteristics associated with receiving a palliative care consult. RESULTS: Among patients with COVID-19 (n=4276; 40%), those with AKI (n=1310; 31%) were more likely than those without AKI (n=2966; 69%) to receive palliative care (AKI without KRT: adjusted odds ratio, 1.81; 95% confidence interval, 1.40 to 2.33; P<0.001; AKI with KRT: adjusted odds ratio, 2.45; 95% confidence interval, 1.52 to 3.97; P<0.001), even after controlling for markers of critical illness (admission to intensive care units, mechanical ventilation, or modified sequential organ failure assessment score); however, consults came significantly later (10 days from admission versus 5 days; P<0.001). Similarly, 66% of patients initiated on KRT received palliative care versus 37% (P<0.001) of those with AKI not receiving KRT, and timing was also later (12 days from admission versus 9 days; P=0.002). Despite greater use of palliative care, patients with AKI had a significantly longer length of stay, more intensive care unit admissions, and more use of mechanical ventilation. Those with AKI did have a higher frequency of discharges to inpatient hospice (6% versus 3%) and change in code status (34% versus 7%) than those without AKI. CONCLUSIONS: Palliative care was utilized more frequently for patients with AKI and COVID-19 than historically reported in AKI. Despite high mortality, consultation occurred late in the hospital course and was not associated with reduced initiation of life-sustaining interventions. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_24_CJN11030821.mp3.