Goldkaya7009

Significantly elevated CBVa was evident in premanifest zQ175 mice prior to motor deficits and striatal atrophy, recapitulating altered CBVa in human premanifest Huntington's disease. CRISPR/Cas9-mediated nonallele-specific HTT silencing in striatal neurons restored altered CBVa in premanifest zQ175 mice, delayed onset of striatal atrophy, and slowed the progression of motor phenotype and brain pathology. This study for the first time shows that a noninvasive functional MRI measure detects therapeutic efficacy in the premanifest stage and demonstrates long-term benefits of a nonallele-selective HTT silencing treatment introduced in the premanifest Huntington's disease.

Abilities and activities that are often simultaneously valued may not be simultaneously achievable for older adults with multi-complexity. Because of this, the Geriatrics 5M's framework prioritizes care on "what matters most." This study aimed to evaluate and refine the What Matters Most-Structured Tool (WMM-ST).

105 older adults with an average of 4 chronic conditions completed the WMM-ST along with open-ended questions from the Serious Illness Conversation Guide. Participants also provided demographic and social information, completed cognitive screening with the T-MoCA-Short and frailty screening with the Frail Scale. Quantitative and qualitative analyses aimed to (1) describe values; (2) evaluate the association of patient characteristics with values, and; (3) assess validity via the tool's (a) acceptability (b) educational bias and (c) content accuracy.

Older adults varied in what matters most. Ratings demonstrated modest associations with social support, religiosity, cognition, and frailty, but not with age or education. The WMM-ST was rated as understandable (86%) and applicable to their current situation (61%) independent of education. Qualitative analyses supported the content validity of WMM-ST, while revealing additional content.

It is possible to assess what matters most to older adults with multi-complexity using a structured tool. Such tools may be useful in making an abstract process clearer but require further validation in diverse samples.

It is possible to assess what matters most to older adults with multi-complexity using a structured tool. Such tools may be useful in making an abstract process clearer but require further validation in diverse samples.

Since the first recognized case of COVID-19, more than 100 million people have been infected worldwide. Global efforts in drug and vaccine development to fight the disease have yielded vaccines and drug candidates to cure COVID-19. However, the spread of SARS-CoV-2 variants threatens the continued efficacy of these treatments. In order to address this, we interrogate the evolutionary history of the entire SARS-CoV-2 proteome to identify evolutionarily conserved functional sites that can inform the search for treatments with broader coverage across the coronavirus family.

Combining coronavirus family sequence information with the mutations observed in the current COVID-19 outbreak, we systematically and comprehensively define evolutionarily stable sites that may provide useful drug and vaccine targets and which are less likely to be compromised by the emergence of new virus strains. Several experimentally-validated effective drugs interact with these proposed target sites. In addition, the same evolutionary information can prioritize cross reactive antigens that are useful in directing multi-epitope vaccine strategies to illicit broadly neutralizing immune responses to the betacoronavirus family. Although the results are focused on SARS-CoV-2, these approaches stem from evolutionary principles that are agnostic to the organism or infective agent.

The results of this work are made interactively available at http//cov.lichtargelab.org.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.Eggplant is rich in anthocyanins, which are thought to be highly beneficial for human health. It has been reported that BICs (blue light inhibitors of Cryptochromes) act as negative regulators in light signal transduction, but little is known about their role in anthocyanin biosynthesis. In this study, yeast one-hybrid analysis showed that SmBICs could bind to the promoter of SmCHS, indicating that they could directly participate in eggplant anthocyanin biosynthesis. In SmBICs-silenced eggplants, more anthocyanins were accumulated, while SmBIC1-OE and SmBIC2-OE Arabidopsis and eggplants synthesized less anthocyanin. qRT-PCR also revealed that the anthocyanin structural genes, which were downregulated in SmBIC1-OE and SmBIC2-OE lines, were upregulated in SmBICs-silenced eggplants. In addition, transcriptome analysis further confirmed that differentially expressed genes of SmBICs-OE plants were enriched mainly in the pathways related to anthocyanin biosynthesis, and the key transcription factors and structural genes for anthocyanin biosynthesis, such as SmMYB1, SmTT8, SmHY5, SmCHS, SmCHI, SmDFR and SmANS, were suppressed significantly. Finally, BiFC and blue light-dependent degradation assay suggested that SmBICs interacted with photo-excited SmCRY2 to inhibit its photoreaction, thereby inhibiting the expression of genes related to anthocyanin biosynthesis and reducing anthocyanin accumulation. Collectively, our study suggests that SmBICs repress anthocyanin biosynthesis by inhibiting photoactivation of SmCRY2. This study provides a new working model for anthocyanin biosynthesis in eggplant.

Increasingly, individuals with atrial fibrillation (AF) use wearable devices (hereafter wearables) that measure pulse rate and detect arrhythmia. The associations of wearables with health outcomes and health care use are unknown.

To characterize patients with AF who use wearables and compare pulse rate and health care use between individuals who use wearables and those who do not.

This retrospective, propensity-matched cohort study included 90 days of follow-up of patients in a tertiary care, academic health system. Included patients were adults with at least 1 AF-specific International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) code from 2017 through 2019. Electronic medical records were reviewed to identify 125 individuals who used wearables and had adequate pulse-rate follow-up who were then matched using propensity scores 4 to 1 with 500 individuals who did not use wearables. Data were analyzed from June 2020 through February 2021.

Using commerciallles by patients with AF, prospective, randomized, long-term evaluation of the associations of wearable technology with health outcomes and health care use is needed.

This study found that follow-up health care use among individuals with AF was increased among those who used wearables compared with those with similar pulse rates who did not use wearables. Given the increasing use of wearables by patients with AF, prospective, randomized, long-term evaluation of the associations of wearable technology with health outcomes and health care use is needed.

Hematopoietic stem cell transplant (HSCT) is an advisable option for refractory or relapsed peripheral T-cell lymphoma (R/R-PTCL), but whether allogeneic HSCT or autologous HSCT is more beneficial is unknown.

To compare the effectiveness and safety of allogeneic HSCT vs autologous HSCT in patients with R/R-PTCL.

A systematic search of the PubMed, Embase, the Cochrane Central Register of Controlled Trials, Wanfang, and China National Knowledge Infrastructure databases with the search items refractory or relapsed peripheral T-cell lymphoma, ASCT/autologous stem-cell transplantation, allo-HSCT/allogeneic stem-cell transplantation, therapeutic effect, and treatment was conducted for articles published from January 12, 2001, to October 1, 2020.

After duplicate and irrelevant publications were discarded, 329 were ineligible according to the inclusion (clinical trials or retrospective studies with >10 samples) and exclusion criteria (articles without overall survival [OS], progression-free survival [PFS],% (95% CI, 2%-23%) were observed.

In this systematic review and meta-analysis, OS and PFS were similar in the allogeneic HSCT and autologous HSCT groups; however, allogeneic HSCT was associated with specific survival benefits among patients with R/R-PTCL.

In this systematic review and meta-analysis, OS and PFS were similar in the allogeneic HSCT and autologous HSCT groups; however, allogeneic HSCT was associated with specific survival benefits among patients with R/R-PTCL.

Poor work-life integration (WLI) occurs when career and personal responsibilities come in conflict and may contribute to the ongoing high rates of physician burnout. The characteristics associated with WLI are poorly understood.

To identify personal and professional factors associated with WLI in physicians and identify factors that modify the association between gender and WLI.

This cross-sectional study was based on electronic and paper surveys administered October 2017 to March 2018 at private, academic, military, and veteran's practices across the US. It used a population-based sample of US physicians across all medical specialties. Data analysis was performed from November 2019 to July 2020.

WLI was assessed using an 8-item scale (0-100 point scale, with higher scores indicating favorable WLI), alongside personal and professional factors. Multivariable linear regressions evaluated independent associations with WLI as well as factors that modify the association between gender and WLI.

Of 5197 ph 95% CI, 68-72; P < .001).

This study found that lower WLI was reported by physicians who are women, single, aged 35 years or older, and who work more hours and call nights. These findings suggest that systemic change is needed to improve WLI among physicians.

This study found that lower WLI was reported by physicians who are women, single, aged 35 years or older, and who work more hours and call nights. These findings suggest that systemic change is needed to improve WLI among physicians.

Outpatient postpartum recovery is an underexplored area of obstetrics. There is currently no consensus regarding which patient-reported outcome measure (PROM) clinicians and researchers should use to evaluate postpartum recovery.

To evaluate PROMs of outpatient postpartum recovery using Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines.

An initial literature search performed in July 2019 identified postpartum recovery PROMs and validation studies. A secondary search in July 2020 identified additional validation studies. Both searches were performed using 4 databases (Web of Science, Embase, PubMed, and CINAHL), with no date limiters. Studies with PROMs evaluating more than 3 proposed outpatient postpartum recovery domains were considered. Studies were included if they assessed any psychometric measurement property of the included PROMs in the outpatient postpartum setting. The PROMs were assessed for the following 8 psychometric measurement properties, as rently available to evaluate outpatient postpartum recovery were the Maternal Concerns Questionnaire, the Postpartum Quality of Life tool, and the World Health Organization Quality of Life-BREF; however, these tools all had significant limitations. This study highlights the need to focus future efforts on robustly developing and validating a new PROM that may comprehensively evaluate outpatient postpartum recovery.