Explore the vast range of titles available.

Meta‐analyses showed that non‐dipping of nocturnal blood pressure on ambulatory blood pressure monitoring (ABPM) was associated with adverse cardiovascular prognosis. However, these prognostic studies were mainly conducted in Caucasian and Japanese populations. Whether this association applies to Chinese patients remained uninvestigated. A total of 1199 Chinese patients with hypertension undergoing ABPM between January 2012 and December 2014 were recruited retrospectively from five public hypertension referral clinics in Hong Kong. Patients were followed up for a mean 6.42 years for cardiovascular morbidity and mortality and all‐cause mortality. Time to event of different dipping patterns was compared by Kaplan‐Meier curves. Hazard ratios (HR) were obtained by Cox proportional hazard models with patient demographics and confounding factors adjusted in multivariate regression. A total of 163 end point events occurred in the period. Normal dipping was observed in 446 patients (37.2%), non‐dipping in 490 (40.9%), reverse dipping in 161 (13.4%), and extreme dipping in 102 (8.5%). Kaplan‐Meier analyses showed inferior survival in non‐dippers and reverse dippers for total cardiovascular events and coronary events but not cerebrovascular events. After adjusting for confounding factors, Cox regressions showed HRs 1.166 (CI 0.770‐1.764) and 1.173 (CI 0.681‐2.021) in non‐dippers and reverse dippers for total cardiovascular events, and HRs 1.320 (CI 0.814‐2.141) and 1.476 (CI 0.783‐2.784) for coronary events. Nocturnal blood pressure non‐dipping, and to a greater extent reverse dipping, demonstrated adverse cardiovascular prognosis in a cohort of Chinese patients with hypertension in Hong Kong. Further focused studies on cerebrovascular events and reverse dippers were warranted to refine risk stratification.

Previously untreated patients with advanced esophageal cancer were randomly assigned to receive chemotherapy alone, chemotherapy plus nivolumab, or nivolumab plus ipilimumab. Among patients with tumor-cell PD-L1 expression of 1% or greater, the two nivolumab regimens resulted in longer overall survival than chemotherapy. The side-effect profile was consistent with past reports on these agents.

After 2 years of follow-up in a randomized trial involving 301 patients with moderate ischemic mitral regurgitation undergoing CABG, the addition of mitral-valve repair did not improve left ventricular function or remodeling. Ischemic mitral regurgitation of moderate severity develops in approximately 10% of patients after myocardial infarction. 1 , 2 Mitral regurgitation is caused by the displacement of papillary muscle, leaflet tethering, reduced closing forces, and annular dilatation. Over time, the condition has an adverse effect on the rate of survival free of heart failure. 3 Because most patients with ischemic mitral regurgitation have multivessel coronary artery disease requiring revascularization, surgeons have to consider whether to add mitral-valve repair to coronary-artery bypass grafting (CABG). The appropriate surgical management of moderate ischemic mitral regurgitation at the time of CABG remains controversial. Some experts advocate revascularization alone . . .

Higher delay discounting (DD) (i.e., propensity to devalue larger, delayed rewards over immediate, smaller rewards) is a transdiagnostic marker underpinning multiple health behaviors. Although genetic influences account for some of the variability in DD among adults, less is known about the genetic contributors to DD among preadolescents. We examined whether polygenic scores (PGS) for DD, educational attainment, and behavioral traits (i.e., impulsivity, inhibition, and externalizing behavior) were associated with phenotypic DD among preadolescents. Participants included youth (N = 8982, 53% male) from the Adolescent Brain Cognitive Development Study who completed an Adjusting Delay Discounting Task at the 1‐year follow‐up and had valid genetic data. PGS for DD, educational attainment, impulsivity, inhibition, and externalizing behaviors were created based on the largest GWAS available. Separate linear mixed effects models were conducted in individuals most genetically similar to European (EUR; n = 4972), African (AFR; n = 1769), and Admixed American (AMR; n = 2241) reference panels. After adjusting for age, sex, income, and the top ten genetic ancestry principal components, greater PGS for DD and lower educational attainment (but not impulsivity, inhibition, or externalizing) were associated with higher rates of DD (i.e., preference for sooner, smaller rewards) in participants most genetically similar to EUR reference panels. Findings provide insight into the influence of genetic propensity for DD and educational attainment on the discounting tendencies of preadolescents, particularly those most genetically similar to European reference samples, thereby advancing our understanding of the etiology of choice behaviors in this population. Greater polygenic scores (PGS) for delay discounting and lower educational attainment were associated with greater delay discounting (i.e., preference for sooner, smaller rewards) among preadolescents most genetically similar to European ancestry reference panels.

Emerging evidence of an altered gut microbiome in autism spectrum disorder (ASD) suggests a pathomechanism through the gut–brain axis despite the inconsistent microbiome profile reported across studies. One of the knowledge gaps in the existing ASD microbiota studies is the lack of systematic exploration of the role of comorbid functional gastrointestinal disorder (FGID) in the association of ASD and altered gut microbiome. Consequently, 92 ASD and 112 age-matched typically developing (TD) boys were profiled on general psychopathology, FGID status by Rome IV classification, and gut microbiota using 16S ribosomal RNA amplicon sequencing at the V4 hypervariable region. Compared to TD, a significant decrease in the within-sample abundance of taxa was observed in ASD, regardless of FGID status. The microbiota of ASD FGID+ and ASD FGID− clustered apart from the TD groups. The microbiota of ASD FGID+ also showed qualitative differences from that of ASD FGID− and had the highest-level Firmicutes: Bacteroidetes ratio, which was paralleled by elevated levels of anxiety and overall psychopathology. The altered gastrointestinal microbiota composition in ASD appeared to be independent of comorbid FGID. Further studies should address how FGID may mediate neuropsychiatric symptoms in ASD through inflammation along the microbiota–gut–brain axis.

Significance Neurons develop processes called neurites to form defined networks. Neurite growth is regulated by many intracellular signaling pathways, among which signaling via phosphatase and tensin homolog (PTEN) is of particular relevance because it controls the translation of a substantial subset of mRNAs that encode proteins with a role in neurite growth. Previous studies indicated that the E3 ubiquitin ligases Nedd4-1 and Nedd4-2 may ubiquitinate and negatively regulate PTEN in various cell types, including Xenopus laevis retinal ganglion cells. We report a strikingly inverted scenario, according to which Nedd4s are dispensable for ubiquitination of PTEN in mammalian central nervous system neurons. Instead, Nedd4-1 mRNA is one of the most important targets of PTEN-dependent signaling in the regulation of neurite growth.

This study demonstrates the impact of adjuvant on the development of T follicular helper (Tfh) and B cells, and their influence on antibody responses in mice vaccinated with SARS-CoV-2-spike-ferritin-nanoparticle (SpFN) adjuvanted with either Army Liposome Formulation containing QS-21 (SpFN + ALFQ) or Alhydrogel ® (SpFN + AH). SpFN + ALFQ increased the size and frequency of germinal center (GC) B cells in the vaccine-draining lymph nodes and increased the frequency of antigen-specific naive B cells. A single vaccination with SpFN + ALFQ resulted in a higher frequency of IL-21-producing-spike-specific Tfh and GC B cells in the draining lymph nodes and spleen, S-2P protein-specific IgM and IgG antibodies, and elicitation of robust cross-neutralizing antibodies against SARS-CoV-2 variants as early as day 7, which was enhanced by a second vaccination. This was associated with the generation of high titer, high avidity binding antibodies. The third vaccination with SpFN + ALFQ elicited high levels of neutralizing antibodies against the Omicron variant. No cross-neutralizing antibodies against Omicron were induced with SpFN + AH. These findings highlight the importance of ALFQ in orchestrating early induction of antigen-specific Tfh and GC B cell responses and long-lived plasma cells in the bone marrow. The early engagement of S-2P specific naive B cells and high titer IgM antibodies shape the development of long-term neutralization breadth.

Metastasis remains the leading cause of cancer mortality, and reactive oxygen species (ROS) signaling promotes the metastatic cascade. However, the molecular pathways that control ROS signaling relevant to metastasis are little studied. Here, we identify SIRT3, a mitochondrial deacetylase, as a regulator of cell migration via its control of ROS signaling. We find that, although mitochondria are present at the leading edge of migrating cells, SIRT3 expression is down-regulated during migration, resulting in elevated ROS levels. This SIRT3-mediated control of ROS represses Src oxidation and attenuates focal adhesion kinase (FAK) activation. SIRT3 overexpression inhibits migration and metastasis in breast cancer cells. Finally, in human breast cancers, SIRT3 expression is inversely correlated with metastatic outcome and Src/FAK signaling. Our results reveal a role for SIRT3 in cell migration, with important implications for breast cancer progression.

The COVID-19 pandemic is spreading across the globe, and it could take years for society to fully recover. Personal protective equipment (PPE), various hygiene measures, and social distancing have been implemented to reduce “human to human” contact, which is an essential part of outbreak prevention. The pressure of the pandemic combined with decreased communication and social contact have taken a toll on the mental health of many individuals, especially with respect to anxiety and depression. Effective use of robots and technology as a substitute for—or in coordination with—traditional medicine could play a valuable role in reducing psychological distress now more than ever. This paper summarizes the results of a comprehensive review of clinical research on PARO, a therapeutic seal robot, which has been used extensively as a biofeedback medical device and socially assistive robot in the field of mental health. PARO has proven to be an effective and economical non-pharmacological intervention method for both mental and physical well-being during the COVID-19 pandemic. Utilization of PARO during these times has provided more data for consideration and has helped in mitigating the negative stigma surrounding using robots in therapeutic settings.

The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants. An adjuvanted SARS-CoV-2 spike-ferritin nanoparticle vaccine can elicit antibodies with relatively broad sarbecovirus activity in non-human primates. Here, the authors isolate and structurally characterize several monoclonal antibodies providing insights into the targeted epitopes and broad reactivity.