MITIGATING OVER-SATURATED FLUORESCENCE IMAGES THROUGH A SEMI-SUPERVISED GENERATIVE ADVERSARIAL NETWORK.

Multiplex immunofluorescence (MxIF) imaging is a critical tool in biomedical research, offering detailed insights into cell composition and spatial context. As an example, DAPI staining identifies cell nuclei, while CD20 staining helps segment cell membranes in MxIF. However, a persistent challenge in MxIF is saturation artifacts, which hinder single-cell level analysis in areas with over-saturated pixels.

First, Do No Harm (to the One You Train).

Unlabelled: or "first, do no harm" is perhaps the most well-known aphorism in the culture of medical education. While its application to patients is well known, the injunction can also be read with medical trainees in mind. Teaching physicians have an obligation to recognize their role as moral teachers and coaches, who must consider "first, do no harm" not only when considering their patients but also when weighing the moral formation of their trainees, especially in a season in which medical educators are attempting to clarify the "harms" of medical training.

Afatinib and Necitumumab in -Mutant NSCLC with Acquired Resistance to Tyrosine Kinase Inhibitors.

Introduction: Although tyrosine kinase inhibitors (TKIs) are effective against NSCLC harboring sensitizing gene mutations, acquired resistance is inevitable. Preclinical studies suggest that combining EGFR TKI and monoclonal antibody therapies may have activity in mutated NSCLC that has progressed on TKI therapy alone. Therefore, we prospectively evaluated afatinib plus necitumumab in patients with mutated NSCLC.

Differential Associations of Cigar, Pipe, and Smokeless Tobacco Use Versus Combustible Cigarette Use With Subclinical Markers of Inflammation, Thrombosis, and Atherosclerosis: The Cross-Cohort Collaboration-Tobacco Working Group.

Background: Understanding the association of tobacco product use with subclinical markers is essential in evaluating health effects to inform regulatory policy. This is particularly relevant for noncigarette products (eg, cigars, pipes, and smokeless tobacco), which have been understudied because of their low prevalence in individual cohort studies.

Methods: This cross-sectional study included 98 450 participants from the Cross-Cohort Collaboration-Tobacco data set.

Longitudinal Symptom Burden and Pharmacologic Management of Catatonia in Autism With Intellectual Disability: An Observational Study.

Catatonia is a highly morbid psychomotor and affective disorder, which can affect autistic individuals with and without intellectual disability. Catatonic symptoms are treatable with pharmacotherapy and electroconvulsive therapy, but the longitudinal effectiveness of these treatments in autistic individuals has not been described. We conducted a prospective observational cohort study of patients with autism and co-morbid catatonia who received outpatient care in a specialized outpatient clinic from July 1, 2021 to May 31, 2024.

Increased unedited Alu RNA patterns found in cortex extracellular vesicles in Alzheimer's disease resemble hippocampus vasculature Alu RNA editing patterns but not cortex Alu RNA editing patterns.

Background: Endogenous Alu RNAs form double-stranded RNAs recognized by double-stranded RNA sensors and activate IRF and NF-kB transcriptional paths and innate immunity. Deamination of adenosines to inosines by the ADAR family of enzymes, a process termed A-to-I editing, disrupts double-stranded RNA structure and prevents innate immune activation. Innate immune activation is observed in Alzheimer's disease, the most common form of dementia.

Maternal Western Diet Programmes Bile Acid Dysregulation and Hepatic Fibrosis in Fetal and Juvenile Macaques.

Background And Aims: Maternal obesity increases the risk of the paediatric form of metabolic dysfunction-associated steatotic liver disease (MASLD), affecting up to 30% of youth, but the developmental origins remain poorly understood.

Methods: Using a Japanese macaque model, we investigated the impact of maternal Western-style diet (mWSD) or chow diet followed by postweaning WSD (pwWSD) or chow diet focusing on bile acid (BA) homeostasis and hepatic fibrosis in livers from third-trimester fetuses and 3-year-old juvenile offspring.

Results: Juveniles exposed to mWSD had increased hepatic collagen I/III content and stellate cell activation in portal regions.

A mixed-methods observational study of strategies for success in implementation science: overcoming emergency departments hurdles.

Background: Heart failure is a major public health concern, affecting 6.7 million Americans. An estimated 16% of emergency department (ED) patients with acute heart failure (AHF) are discharged home.

Practice Advisory for Postoperative Pain Management of Thoracic Surgical Patients: Executive Summary: A Report by Society of Cardiovascular Anesthesiologists.

Patients after thoracic surgery experience significant pain that can disrupt normal respiratory mechanics, increase the risk of respiratory complications, and impair recovery. Poorly controlled postoperative pain can develop into persistent postoperative pain. In addition, using opioids for pain control in the thoracic surgical population makes them more susceptible to opioid-related side effects due to their pre-existing comorbidities.

Estimating the generation time for influenza transmission using household data in the United States.

The generation time, representing the interval between infections in primary and secondary cases, is essential for understanding and predicting the transmission dynamics of seasonal influenza, including the real-time effective reproduction number (Rt). However, comprehensive generation time estimates for seasonal influenza, especially since the 2009 influenza pandemic, are lacking. We estimated the generation time utilizing data from a 7-site case-ascertained household study in the United States over two influenza seasons, 2021/2022 and 2022/2023.

Short and mid-term research priorities for Veterans with multiple sclerosis: A modified Delphi process engaging Veterans, researchers, and operational partners.

Background/objective: Identifying research priorities of Veterans, MS researchers, and key stakeholders is critical to advance high-quality, evidence-based, and Veteran-specific MS care.

Methods: We used a modified Delphi approach to identify research priorities for Veterans with MS. Electronic surveys were distributed to Veterans with MS (n = 50,975), MS researchers (n = 191), VA healthcare providers (1,337), and funding agency representatives (n = 6) asking about their 2-3 most important research questions that would benefit Veterans with MS for researchers to answer in the next 5-10 years.

Viral Transcript and Tumor Immune Microenvironment-Based Transcriptomic Profiling of HPV-Associated Head and Neck Squamous Cell Carcinoma Identifies Subtypes Associated with Prognosis.

Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HPV-positive HNSCC) has distinct biological characteristics from HPV-negative HNSCC. Using an AI-based analytical platform on meta cohorts, we profiled expression patterns of viral transcripts and HPV viral genome integration, and classified the tumor microenvironment (TME). Unsupervised clustering analysis revealed five distinct and novel TME subtypes across patients (immune-enriched, highly immune and B-cell enriched, fibrotic, immune-desert, and immune-enriched luminal).

Magnesium Depletion Score and Mortality in Individuals with Metabolic Dysfunction Associated Steatotic Liver Disease over a Median Follow-Up of 26 Years.

Unlabelled: Metabolic dysfunction associated steatotic liver disease (MASLD) has been associated with increased risks of all-cause and cardiovascular disease (CVD) mortality. Identification of modifiable risk factors that may contribute to higher risks of mortality could facilitate targeted and intensive intervention strategies in this population. This study aims to examine whether the magnesium depletion score (MDS) is associated with all-cause and CVD mortality among individuals with MASLD or metabolic and alcohol associated liver disease (MetALD).

Plasma Endothelin-1 Levels: Non-Predictors of Alzheimer's Disease Reveal Age Correlation in African American Women.

Alzheimer's disease (AD) and related dementias (ADRD) disproportionately impact racial and ethnic minorities. Contributing biological factors that explain this disparity have been elusive. Moreover, non-invasive biomarkers for early detection of AD are needed.

Differences in Characteristics of Peripartum Patients Who Did and Did Not Require an Upgrade to the Intensive Care Unit: A Propensity Score Matching Study.

This study sought to identify predictors for peripartum patients admitted to non-intensive care wards who later upgraded to the Intensive Care Unit (ICU). This was a retrospective observational study of patients admitted to the Maternal Fetal Ward between 01/2017 and 12/2022, who later upgraded to the ICU. Upgraded patients were 1:1 propensity score matched with those who remained on the Maternal Fetal Ward (control).

The Clinical Utility of a Next-Generation Sequencing-Based Approach to Detecting Circulating HPV DNA in Patients with Advanced Anal Cancer.

Background: To extend the practicality of liquid biopsy beyond the historical HPV circulating tumor DNA (ctDNA) assays, we evaluated the clinical relevance of a novel next-generation sequencing HPV ctDNA assay in patients with locally advanced and metastatic squamous cell cancer of the anal canal (mSCCA).

Methods: ctDNA isolated from the plasma of patients with mSCCA was sequenced using a 1.4 Mb hybrid-capture target-enrichment panel covering the whole genome sequences of all 193 HPV types.

Next-Generation Immunotherapy for Hepatocellular Carcinoma: Mechanisms of Resistance and Novel Treatment Approaches.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and, with only 15-20% of HCC patients being suitable for potentially curative treatments, the vast majority of patients with HCC ultimately require systemic therapy. For decades, the choice of effective systemic therapy for HCC remained sparse. In recent years, after the combination of atezolizumab and bevacizumab demonstrated superior overall survival over the first-line standard, sorafenib, there has been a major therapeutic paradigm shift to immunotherapy-based regimens for HCC.

A randomized, placebo-controlled, cross-over trial of ketamine in Rett syndrome.

Background: Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy.

Design: This was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence, cross-over study of oral ketamine in 6-12-year-old girls with RTT to evaluate short-term safety and tolerability and explore efficacy.

Methods: Participants were randomized to either five days treatment with oral ketamine or matched placebo, followed by a nine-day wash-out period and then crossed-over to the opposite treatment.

Immune evasion in ovarian cancer: implications for immunotherapy and emerging treatments.

Ovarian cancer (OC) is the most lethal gynecologic malignancy, characterized by multiple histological subtypes, each with distinct pathological and clinical features. Current treatment approaches include cytotoxic chemotherapies, poly(ADP-ribose) polymerase (PARP) inhibitors, bevacizumab, hormonal therapy, immunotherapy, and antibody-drug conjugates (ADCs). In this review we discuss immune evasion mechanisms in OC and the role of genetics, the tumor microenvironment, and tumor heterogeneity in influencing these processes.

Practice Advisory for Postoperative Pain Management of Cardiac Surgical Patients: A Report by Society of Cardiovascular Anesthesiologists.

Moderate to severe pain after cardiac surgery is relatively common, which increases the risk of postoperative cardiopulmonary complications and delays hospital discharge. Opioids have been useful agents for postoperative pain control after cardiac surgery, but are associated with serious adverse effects. As a result, multimodal analgesia has been adopted widely to decrease reliance on opioids for treating postoperative pain, reduce opioid-related adverse effects, and promote early recovery.

TET2-loss enhances immediate and time-resolved IFNγ signaling responses across myeloid differentiation.

Signaling responses to cytokines are disrupted in clonal hematopoiesis and myeloid malignancies. To better identify specific signaling response alterations in the presence or absence of TET2, we developed a 36-parameter CyTOF panel of both surface marker and phosphoprotein antigens in murine BM. We show diverse, cell-type specific inflammatory cytokine responses in healthy hematopoietic cells.