Clinicogenomic landscape of pancreatic adenocarcinoma identifies KRAS mutant dosage as prognostic of overall survival.

Nearly all pancreatic adenocarcinomas (PDAC) are genomically characterized by KRAS exon 2 mutations. Most patients with PDAC present with advanced disease and are treated with cytotoxic therapy. Genomic biomarkers prognostic of disease outcomes have been challenging to identify.

Habitual preexercise caffeine supplementation prevents exercise training-induced attenuation of exercising systolic blood pressure and double product.

We examined the effect of habitual preexercise caffeine supplementation on training-induced adaptations to exercising systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), heart rate (HR), and double product (DP). Young women (means ± SD; 24 ± 7 yr) were randomized to a caffeine (120 mg) supplement (CAF; = 17) or placebo (PLA; = 16) group, completed 6 wk of high-intensity exercise training on three nonconsecutive days per week, and supplemented with CAF or PLA 30-60 min before exercise or else upon waking. Before (PRE) and after (POST) the intervention, SBP, DBP, and HR were measured and PP and DP were calculated, at rest and during fixed-power exercise at 50 and 75 W.

Depression and Anxiety Among US Children and Young Adults.

Importance: Data from surveys show increased mental health disorders in youths. However, little is known about clinical diagnosis over time.

Objective: To assess the incidence, prevalence, and changes from 2017 to 2021 for depression and anxiety diagnosed clinically among children, adolescents, and young adults and to identify potential disparities.

Acute, dose-response effects of guayusa leaf extract on mood, cognitive and motor-cognitive performance, and blood pressure, heart rate, and ventricular repolarization.

Purpose: We conducted a randomized, double-blind, placebo-controlled crossover trial in young adults to examine the dose-dependent (600 mg versus 1200 mg), acute effects of consumption of an tea extract (GLE) on mood, cognitive and motor-cognitive performance, as well as its acute cardiovascular effects.

Methods: Twenty-five adults (mean ± SD, age = 28 ± 7 y; 9 M/16 F) completed familiarization and then three randomly ordered experimental visits where they consumed either 600 mg (GLE) or 1200 mg (GLE) GLE or placebo (PLA). Following supplement consumption, participants completed a mood state survey, assessments of perceived jitteriness, energy, and focus, and neurocognitive and motor-cognitive testing.

Cemiplimab-Induced Hyperosmolar Hyperglycemic State With Concurrent Diabetic Ketoacidosis in a Patient Receiving Treatment for Cutaneous Squamous Cell Carcinoma.

The immune checkpoint inhibitor (ICI) cemiplimab is a human monoclonal antibody used in the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma (CSCC) not amenable to surgery or radiation therapy. Although cemiplimab shows excellent efficacy with a good tolerability profile, it can cause side effects, including potentially life-threatening endocrinopathies. We discuss the case of a 77-year-old Caucasian female with CSCC treated with only three cycles of cemiplimab who presented with altered mental status and was found to have severe hyperglycemia, hyperosmolarity, ketonemia, glucosuria, and ketonuria concerning for hyperosmolar hyperglycemic syndrome (HHS) with concurrent diabetic ketoacidosis (DKA).

Autistic Traits Associated with the Fragile X Premutation Allele: The Neurodevelopmental Profile.

Although most individuals who carry the Fragile X premutation allele, defined as 55-200 CGG repeats on the X-linked gene ( gene), do not meet diagnostic criteria for autism spectrum disorder, there is a suggestion of increased behaviors associated with subtle autistic traits. More autism associated characteristics have been reported among adults than children. This may highlight a possible worsening developmental trajectory, variable findings due to research quality or differences in number of studies done in adults vs children, rather than true developmental changes.

Climate variability on Fit for 55 European power systems.

The use of variable renewable energy sources to generate electricity introduces a dependency on meteorological factors into power systems. With the renewables share growing globally, often driven by political pressures, the reliability and efficiency of power systems are increasingly affected by this dependency. In this paper, we investigate the impact of the natural variability of meteorological parameters on the European power system in 2030.

Application of high-throughput single-nucleus DNA sequencing in pancreatic cancer.

Despite insights gained by bulk DNA sequencing of cancer it remains challenging to resolve the admixture of normal and tumor cells, and/or of distinct tumor subclones; high-throughput single-cell DNA sequencing circumvents these and brings cancer genomic studies to higher resolution. However, its application has been limited to liquid tumors or a small batch of solid tumors, mainly because of the lack of a scalable workflow to process solid tumor samples. Here we optimize a highly automated nuclei extraction workflow that achieves fast and reliable targeted single-nucleus DNA library preparation of 38 samples from 16 pancreatic ductal adenocarcinoma patients, with an average library yield per sample of 2867 single nuclei.

Synthesis of 7-Aminocoumarins from 7-Hydroxycoumarins via Amide Smiles Rearrangement.

N-Substituted 7-aminocoumarins can be synthesized from readily available 7-hydroxycoumarins via alkylation with α-bromoacetamides and subsequent tandem O → N Smiles rearrangement-amide hydrolysis. The key rearrangement sequence proceeds under mild conditions to provide convenient access to various -alkyl and -aryl products in moderate to high yields. The process is operationally simple, inexpensive, transition-metal-free, and can be telescoped into a one-pot process.

Improving Survival Prognostication in Patients With Metastatic Cancer Through Clinical Judgment.

Background/aim: NEAT is a validated prognostic model that calculates survival estimates based on the number of active tumors, ECOG performance status, albumin, and primary tumor site. Since models are imperfect, we hypothesized that experienced clinicians could predict the survival of patients with metastatic cancer better than a validated prognostic model alone, thereby quantifying the previously unmeasured value of clinical judgment.

Patients And Methods: This prospective, single-institution cohort study conducted at a large community hospital recruited 73 patients with metastatic cancer referred to radiation oncology between October 2016 and December 2017.

The Sexual Rights of Others: Majoritized Women's Support for Marginalized Women's Sexual Rights.

Advocates argue that sexual safety, access to sexuality-related services, sexual health and well-being, sexual privacy, and sexual autonomy are universal and inalienable rights of all people. However, for those relegated to the social, economic, and political margins, their sexual rights can only be secured with the support of others. In the current study, we examined whether a sample of 307 majoritized women (i.

Reduced thrombogenicity of surface-treated Nitinol implants steered by altered protein adsorption.

Blood-contacting medical implants made of Nitinol and other titanium alloys, such as neurovascular flow diverters and peripheral stents, have the disadvantage of being highly thrombogenic. This makes the use of systemic (dual) anti-platelet/anticoagulant therapies inevitable with related risks of device thrombosis, bleeding and other complications. Meeting the urgent clinical demand for a less thrombogenic Nitinol surface, we describe here a simple treatment of standard, commercially available Nitinol that renders its surface ultra-hydrophilic and functionalized with phosphate ions.

Association of radiation dose intensity with overall survival in patients with distant metastases.

Background: Patients with metastatic cancer referred to radiation oncology have diverse prognoses and there is significant interest in personalizing treatment. We hypothesized that patients selected for higher biologically equivalent doses have improved overall survival.

Methods: The study population consists of 355 consecutive adult patients with distant metastases treated by a single radiation oncologist from 2014 to 2018.

Quality of the sibling relationship when one sibling has autism spectrum disorder: A randomized controlled trial of a sibling support group.

The sibling relationship can be negatively impacted when one child has autism spectrum disorder. One way to improve the quality of that relationship is through typically developing sibling participation in a support group in which they learn about autism spectrum disorder and coping skills, develop a peer network, and discuss their feelings. Compared to participating in a similar group without a focus on autism spectrum disorder, siblings in the support group showed improvements in the quality of the sibling relationship.

The Genetic Evolution of Treatment-Resistant Cutaneous, Acral, and Uveal Melanomas.

Purpose: Melanoma is a biologically heterogeneous disease composed of distinct clinicopathologic subtypes that frequently resist treatment. To explore the evolution of treatment resistance and metastasis, we used a combination of temporal and multilesional tumor sampling in conjunction with whole-exome sequencing of 110 tumors collected from 7 patients with cutaneous ( = 3), uveal ( = 2), and acral ( = 2) melanoma subtypes.

Experimental Design: Primary tumors, metastases collected longitudinally, and autopsy tissues were interrogated.

Prognostic role of baseline neutrophil-to-lymphocyte ratio in metastatic solid tumors.

High baseline neutrophil-to-lymphocyte ratio (NLR) has been associated with poor survival in a number of solid tumors, but has not been extensively investigated in the context of radiation oncology. Developing more robust models to predict survival would inform patient care for patients with metastatic solid tumors. The present study was undertaken to evaluate the effect of baseline NLR (using 4 as a cutoff) on survival in 320 consecutive patients with metastatic cancer who were referred to a single radiation oncologist between 2012 and 2015, with a median follow-up of 20.

Distinct infrastructure of lipid networks in visceral and subcutaneous adipose tissues in overweight humans.

Background: Adipose tissue plays important roles in health and disease. Given the unique association of visceral adipose tissue with obesity-related metabolic diseases, the distribution of lipids between the major fat depots located in subcutaneous and visceral regions may shed new light on adipose tissue-specific roles in systemic metabolic perturbations.

Objective: We sought to characterize the lipid networks and unveil differences in the metabolic infrastructure of the 2 adipose tissues that may have functional and nutritional implications.

Quantifying intersectionality: An important advancement for health inequality research.

Background: Intersectionality is a powerful theoretical framework that is useful in describing the lived experiences of people with multiple marginalized statuses. By focusing on power and domination (e.g.

If It Wasn't Rape, Was It Sexual Assault? Comparing Rape and Sexual Assault Acknowledgment in College Women Who Have Experienced Rape.

The present study investigated (a) comparisons in rates of rape and sexual assault acknowledgment and (b) a comprehensive multivariate multinomial logistic model predicting rape and sexual assault acknowledgment in a sample of 174 college women who had experienced rape. Significantly more women acknowledged having experienced sexual assault than rape. Greater perceived perpetrator force was associated with increased likelihood of rape and sexual assault acknowledgment.

Minimal functional driver gene heterogeneity among untreated metastases.

Metastases are responsible for the majority of cancer-related deaths. Although genomic heterogeneity within primary tumors is associated with relapse, heterogeneity among treatment-naïve metastases has not been comprehensively assessed. We analyzed sequencing data for 76 untreated metastases from 20 patients and inferred cancer phylogenies for breast, colorectal, endometrial, gastric, lung, melanoma, pancreatic, and prostate cancers.

Patients with Rheumatic Diseases do not have an Increased Risk of MRSA Carrier Status.

Introduction: The aim of this study was to determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) both in rheumatologic and non-rheumatologic rehabilitation centers. In addition, we sought to evaluate the practice value of existing screening recommendations of the German Commission for Hospital Hygiene and Infection Prevention (KRINKO).

Methods: The analysis was performed in four rehabilitation clinics (rheumatology, psychosomatic medicine, oncology, and cardiology) with at least 200 patients per clinic tested for MRSA.

Reconsolidation of appetitive odor discrimination requires protein synthesis only when reactivation includes prediction error.

Reconsolidation theory has supported the notion that active memory is vulnerable to the effects of an amnesic agent. An extension of reconsolidation theory posits that active memory, while necessary for creating vulnerability in memory, is not sufficient. Prediction error (i.

The NEAT Predictive Model for Survival in Patients with Advanced Cancer.

Purpose: We previously developed a model to more accurately predict life expectancy for stage IV cancer patients referred to radiation oncology. The goals of this study are to validate this model and to compare competing published models.

Materials And Methods: From May 2012 to March 2015, 280 consecutive patientswith stage IV cancerwere prospectively evaluated by a single radiation oncologist.

Effect of modern, high-quality prostate intensity-modulated radiation therapy on outcome: Evidence from a community radiation oncology program.

Radiation technique for prostate cancer has continuously evolved over the past several decades. The aim of the present study was to describe the effects of implementing modern prostate intensity-modulated radiation therapy (M-IMRT) on dosimetry and outcome. Between January 2010 and April 2012, 48 consecutive patients were treated with conventional prostate IMRT (C-IMRT) to a dose of 81 Gy.