Ultra-sensitive, tumor-informed ctDNA profiling in pembrolizumab-treated esophagogastric cancer patients predicts clinical responses.

To explore whether ultra-sensitive circulating tumor DNA (ctDNA) profiling enables early prediction of treatment response and early detection of disease progression, we applied NeXT Personal, an ultra-sensitive bespoke tumor-informed liquid biopsy platform, to profile tumor samples from the KeyLargo study, a phase II trial in which metastatic esophagogastric cancer (mEGC) patients received capecitabine, oxaliplatin, and pembrolizumab. All 25 patients evaluated were ctDNA-positive at baseline. Minimal residual disease (MRD) events varied from 406,067 down to 1.

Failure to oxygenate during cardiopulmonary bypass; treatment options and intervention algorithm.

Membrane oxygenator failure remains a concern for perfusion teams. Successful outcomes for this low-frequency, high-risk intervention are predicated on having written institutional protocols for both the oxygenator change-out procedure as well as how often the procedure is practiced by staff perfusionists. A recent review of peer-reviewed journal articles, textbooks and online resources revealed a lack of a unified intervention algorithm for failure to oxygenate during cardiopulmonary bypass (CPB).

TPR is required for cytoplasmic chromatin fragment formation during senescence.

During oncogene-induced senescence there are striking changes in the organisation of heterochromatin in the nucleus. This is accompanied by activation of a pro-inflammatory gene expression programme - the senescence-associated secretory phenotype (SASP) - driven by transcription factors such as NF-κB. The relationship between heterochromatin re-organisation and the SASP has been unclear.

Air-conduction and bone-conduction reference threshold levels-A multicenter studya).

Air-conduction (AC) and bone-conduction (BC) thresholds were measured to evaluate standard reference thresholds and recommend revisions to audiometer standards. AC and BC thresholds were measured from listeners with normal hearing (NH) and sensorineural hearing loss (SNHL) at three sites. NH participants (n = 53) were selected based on age (18-25 years old), normal AC thresholds, tympanometry, otoscopy, and absence of otologic disease.

Unexpected delivery: cryptic pregnancy.

Cryptic pregnancy was first described in the early 17th century and occurs when the pregnant person is unaware of their pregnant state and discovers this late in pregnancy or when labour starts. Historically, the term 'concealed pregnancy' has been used synonymously. In a concealed pregnancy, the patient is aware of their pregnancy but chooses to hide it.

Recommended Physiotherapy Modalities for Oncology Patients with Palliative Needs and Its Influence on Patient-Reported Outcome Measures: A Systematic Review.

Background: This review aims to explore the role of physiotherapy in early and traditional palliative care (PC) for oncology patients, focusing on its impact on six patient-reported outcomes (PROMs), namely fatigue, pain, cachexia, quality of life (QoL), physical functioning (PHF), and psychosocial functioning (PSF). The purpose is to assess the effectiveness of various physiotherapy interventions and identify gaps in the current research to understand their potential benefits in PC better.

Methods: A systematic literature search was conducted across PubMed, Embase, and Web of Science, concluding on 21 December 2023.

It's Not Just What Parents Say, It's Why They Say It: Students' Perceptions of Parents' Motives for Alcohol Communication.

Objective: Previous work has investigated parents' reports of motives for communicating with their young adults about alcohol. While parents' self-reported motives may predict intentions to communicate, young adults' perceptions of their parents' motives may be important for understanding young adults' responses to parent alcohol communication. The present study was conducted to explore college students' perceptions of their parents' motives for alcohol communication and to investigate whether perceptions of these motives predict changes in alcohol consumption and related consequences during the transition to college.

Caesarean sections, indications and outcomes: a cross-sectional study using the Robson classification in a tertiary hospital in Sierra Leone.

Objective: WHO recommends the use of the Robson's 'Ten Groups Classification' for monitoring and assessing caesarean section (CS) rates. The aim of this study was to investigate the rates, indications and outcomes of CS using Robson classification in a tertiary hospital in Sierra Leone.

Design: Cross-sectional study.

Do compulsory mental health patients have a right to receive a second opinion on their treatment under Australian mental health legislation?

We reviewed Australian mental health legislation to determine what obligations it places on psychiatrists to facilitate second opinions for compulsory patients who request them. Only four jurisdictions-Australian Capital Territory, Queensland, Victoria, and Western Australia-have legislated for 'patient-initiated' second opinions. Within these four regimes, there is variation in important aspects of the second opinion process, and there is a general absence of direction given to the second opinion providers.

Circulating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma.

While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA levels and survival have not been examined. Here we investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall and progression-free survival (OS/PFS) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) for patients receiving chemoimmunotherapy ("PRINCE", NCT03214250), and an independent cohort receiving standard of care (SOC) chemotherapy. For PRINCE, higher baseline plasma levels are associated with worse OS for ctKRAS G12D (log-rank p = 0.

Enhanced RHO-ROCK signaling is associated with CRELD2 production and fibroblast recruitment in cutaneous squamous cell carcinoma.

A key characteristic of cancer cells is their ability to induce changes in their microenvironment that render it permissive to tumor growth, invasion and metastasis. Indeed, these changes are required for tumor progression. Consequently, the tumor microenvironment is emerging as a key source of new targets against cancer, with novel therapies aimed at reversing tumor-promoting changes, reinstating a tumor-hostile microenvironment and suppressing disease progression.

Changes in Parent-Student Text Message and Phone Call Communication During the Transition to College as Predictors of Cannabis and Simultaneous Use During the First Year.

Parent communication can be protective against cannabis use among young adults. However, changes in parent-student communication frequency naturally occur during the transition from high school to college. Recent research suggests declines in parent-student communication frequency predict increased drinking and consequences during the first year of college, yet these effects on other risky behaviors are unknown.

Superior functional outcome following reverse shoulder arthroplasty compared to hemiarthroplasty for displaced three- and four-part fractures in patients 65 and older: results from a prospective multicenter randomized controlled trial - The shoulder hemiarthroplasty or reverse polarity arthoplasty (SHeRPA) trial.

Background: Acute unreconstructible 3- or 4-part proximal humerus fractures can be treated with hemiarthroplasty or reverse polarity shoulder arthroplasty. Randomized trials using implants from multiple different companies or uncemented implants have found superior results with reverse polarity arthroplasty.

Hypothesis: We tested the hypothesis that cemented reverse polarity arthroplasty produces a superior outcome compared to cemented hemiarthroplasty using one implant system in patients aged 65 years and over at 12 months follow-up as measured with the Constant Score.

Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in the United Kingdom: A real-world intention-to-treat analysis.

Brexucabtagene autoleucel (brexu-cel) is an autologous CD19 CAR T-cell product, approved for relapsed/refractory (r/r) mantle cell lymphoma (MCL). In ZUMA-2, brexu-cel demonstrated impressive responses in patients failing ≥2 lines, including a bruton's tyrosine kinase inhibitor, with an overall and complete response rate of 93% and 67%, respectively. Here, we report our real-world intention-to-treat (ITT) outcomes for brexu-cel in consecutive, prospectively approved patients, from 12 institutions in the United Kingdom between February 2021 and June 2023, with a focus on feasibility, efficacy, and tolerability.

Professional Values and Mental Health Tribunals: How Healthcare Professionals' and Lawyers' Views Are Shaped by Values, and How This Might Impede Reform.

Most countries that provide for compulsory treatment for mental illness have a system by which this treatment is subject to independent legal oversight. Many countries use a special type of legal body for this purpose, called a mental health tribunal. Mental health tribunals have been subject to criticism from the points of view of both legal professionals and mental healthcare practitioners.

Behavioral trade-offs and multitasking by elk in relation to predation risk from Mexican gray wolves.

Predator non-consumptive effects (NCE) can alter prey foraging time and habitat use, potentially reducing fitness. Prey can mitigate NCEs by increasing vigilance, chewing-vigilance synchronization, and spatiotemporal avoidance of predators. We quantified the relationship between Mexican wolf () predation risk and elk () behavior.

Transcription decouples estrogen-dependent changes in enhancer-promoter contact frequencies and spatial proximity.

How enhancers regulate their target genes in the context of 3D chromatin organization is extensively studied and models which do not require direct enhancer-promoter contact have recently emerged. Here, we use the activation of estrogen receptor-dependent enhancers in a breast cancer cell line to study enhancer-promoter communication at two loci. This allows high temporal resolution tracking of molecular events from hormone stimulation to efficient gene activation.

Irritable Bowel Syndrome in Veterans With Gulf War Illness Evaluated at VA's War-Related Illness and Injury Study Center.

Introduction: Excess rates of Gulf War illness (GWI) and irritable bowel syndrome (IBS), two chronic multisymptom illnesses, have long been documented among nearly 700,000 veterans who served in the 1990-1991 Persian Gulf War. We sought to report the prevalence, characteristics, and association of GWI and IBS decades after the war in a clinical cohort of deployed Gulf War veterans (GWVs) who were evaluated at the Department of Veterans Affairs' War Related Illness and Injury Study Center (WRIISC) for unexplained chronic symptoms.

Materials And Methods: We analyzed data gathered from clinical intake questionnaires of deployed GWVs who were evaluated at WRIISC clinics between 2008 and 2020.

Impacts of human mobility on the citywide transmission dynamics of 18 respiratory viruses in pre- and post-COVID-19 pandemic years.

Many studies have used mobile device location data to model SARS-CoV-2 dynamics, yet relationships between mobility behavior and endemic respiratory pathogens are less understood. We studied the effects of population mobility on the transmission of 17 endemic viruses and SARS-CoV-2 in Seattle over a 4-year period, 2018-2022. Before 2020, visits to schools and daycares, within-city mixing, and visitor inflow preceded or coincided with seasonal outbreaks of endemic viruses.

Design and Methods of the Early Age-Related Hearing Loss Investigation Randomized Controlled Trial.

Objective: Hearing loss has been identified as a major modifiable risk factor for cognitive decline. The Early Age-Related Hearing Loss Investigation (EARHLI) study will assess the mechanisms linking early age-related hearing loss (ARHL) and cognitive impairment.

Study Design: Randomized, controlled, single-site, early phase II, superiority trial.

Process Evaluation and Investigation of Cultural Adaptations for an Online Parent-Based Intervention Using a Mixed-Method Approach.

Most alcohol intervention research focuses on program efficacy, yet few studies have investigated the acceptability of a program's design and implementation to the target population or adapting existing alcohol interventions to different populations. To address these gaps in the literature, we (1) examined participant responsiveness to and implementation quality of FITSTART+, a web-app delivered parent-based alcohol intervention designed for incoming first-year college students in the United States, and (2) gathered feedback on how this intervention could be adapted to other populations of parents. A sample of U.

Pregnancy in patients with the Fontan operation.

Improved survival rates for patients with a Fontan circulation has allowed more women with this complex cardiac physiology to contemplate pregnancy. However, pregnancy in women with a Fontan circulation is associated with a high risk of adverse maternal and foetal outcomes, high rates of miscarriage, and preterm delivery. Factors associated with a successful pregnancy outcome are younger age, normal body weight, absence of significant functional limitation, no Fontan-related complications, and well-functioning single ventricle physiology.

CB307: A Dual Targeting Costimulatory Humabody VH Therapeutic for Treating PSMA-Positive Tumors.

Purpose: CD137 is a T- and NK-cell costimulatory receptor involved in consolidating immunologic responses. The potent CD137 agonist urelumab has shown clinical promise as a cancer immunotherapeutic but development has been hampered by on-target off-tumor toxicities. A CD137 agonist targeted to the prostate-specific membrane antigen (PSMA), frequently and highly expressed on castration-resistant metastatic prostate cancer (mCRPC) tumor cells, could bring effective immunotherapy to this immunologically challenging to address disease.