A concise review on MDM2 inhibitors and recent progress in radiopharmaceutical development for imaging MDM2 expression in tumors with PET or SPECT.

Murine double minute 2 (MDM2, also known as human double minute 2 or HDM2) is a negative regulator of the tumor suppressor protein p53 and is overexpressed in many cancers. Over the past two decades, substantial progress has been made in developing inhibitors of the MDM2-p53 interaction, thereby allowing the p53 protein to exert antitumor effects through cell apoptosis and cycle arrest. While there are currently no FDA-approved MDM2 inhibitors available, several small molecule MDM2 inhibitors and a stapled peptide inhibitor of the MDM2-p53 interaction are in clinical development.

Immunotherapy for resectable NSCLC: neoadjuvant/perioperative followed by surgery over surgery followed by adjuvant. Systematic review and meta-analysis with subgroup analyses.

Background: Immunotherapy has rapidly changed the treatment of early-stage non-small-cell lung cancer (NSCLC) in recent years. We aimed to summarize available evidence on the use of immunotherapy in neoadjuvant/perioperative and adjuvant settings for resectable NSCLC and explore some controversial subgroups.

Materials And Methods: Systematic literature research was carried out for randomized controlled trials of neoadjuvant/perioperative chemo-immunotherapy or adjuvant immunotherapy for resectable NSCLC.

Neural evidence for modality-independent storage in working memory.

Working memory (WM) is a core component of intellectual ability. Traditional behavioral accounts have argued that there remain distinct memory systems based on the type and sensory modality of information being stored. However, more recent work has provided evidence for a class of neural activity that indexes the number of visual items stored in a content-independent fashion.

Changes in Cost of Guideline-Concordant Cancer Treatment: Observations and Implications.

Purpose: Cost of cancer care in the United States is substantial. Previous studies have explored pricing comparisons at the level of individual cancer drugs but not that of clinical indications. This study evaluates cost patterns for providing the best guideline-concordant therapy for solid tumor treatment indications.

The problem-solving role of the 'wait and repeat CT' approach in the diagnosis and treatment of acute abdomen.

Background: This study aims to assess the diagnostic value and problem-solving utility of follow-up abdominopelvic computed tomography (CT) scans performed within 10 days of the initial presentation for acute non-traumatic abdominal symptoms in the emergency department.

Methods: A retrospective analysis was conducted on patients who presented with acute abdominal symptoms to the emergency department between January 1, 2013 and May 30, 2023, and underwent abdominopelvic CT scans in the acute setting. Among this cohort, 149 patients had repeat abdominopelvic CT scans during the same admission and were classified into five groups based on findings: Group A (no change in diagnosis), Group B (confirmation of suspected initial diagnosis), Group C (disease progression), Group D (disease regression), and Group E (new diagnosis).

Daily Assessment of Positive and Negative Cannabis Use Expectancies in Young Adult Cannabis and Tobacco Co-Users: Differences by Sociodemographics, Mental Health Symptoms, and Possible Cannabis Use Disorder.

Objective: Expectancies play a critical role in cannabis use behavior and are influenced by sociodemographic and intrapersonal factors. This study examined daily endorsement of positive and negative cannabis use expectancies using 28 days of ecological momentary assessments (EMAs) in relation to sociodemographics, mental health symptoms, and cannabis use disorder (CUD) among young adult cannabis-tobacco co-users.

Method: Ninety-seven young adult (ages 18-24) cannabis and tobacco co-users reported on anxiety symptoms, depressive symptoms, and possible CUD at baseline.

From relaxation to buckling: A continuum elastic framework connecting surface instabilities of highly compressed lipid thin films.

Self-assembled thin films respond to external loads via surface instabilities that are critical to their functionality in both biology and technology. Lipid monolayers at the air-liquid interface are one such system. Tunability between out-of-plane buckling (e.

Exploring superior capsular reconstruction and tendon transfers for massive irreparable posterosuperior rotator cuff tears.

Rotator cuff tears are prevalent, affecting 20% of the general population, with massive tears accounting for 40% of these cases. Massive tears, those larger than 5 cm or involving several tendons, pose substantial clinical problems, including poorer surgical outcomes and increased recurrence rates. Multiple classification systems offer varied definitions, complicating treatment strategies.

Functional Relevance of CASP16 Nucleic Acid Predictions as Evaluated by Structure Providers.

Accurate biomolecular structure prediction enables the prediction of mutational effects, the speculation of function based on predicted structural homology, the analysis of ligand binding modes, experimental model building, and many other applications. Such algorithms to predict essential functional and structural features remain out of reach for biomolecular complexes containing nucleic acids. Here, we report a quantitative and qualitative evaluation of nucleic acid structures for the CASP16 blind prediction challenge by 12 of the experimental groups who provided nucleic acid targets.

PICALM Alzheimer's risk allele causes aberrant lipid droplets in microglia.

Despite genome-wide association studies (GWAS) of late-onset Alzheimer's disease (LOAD) having identified many genetic risk loci, the underlying disease mechanisms remain largely unclear. Determining causal disease variants and their LOAD-relevant cellular phenotypes has been a challenge. Here, using our approach for identifying functional GWAS risk variants showing allele-specific open chromatin, we systematically identified putative causal LOAD-risk variants in human induced pluripotent stem (iPS)-cell-derived neurons, astrocytes and microglia, and linked a PICALM LOAD-risk allele to a microglial-specific role of PICALM in lipid droplet (LD) accumulation.

Barriers and facilitators to emergency contraception access among university students: Vending machines as a potential solution.

This study investigates the barriers and facilitators to emergency contraception (EC) use among university students and assesses interest in vending machines that sell EC on university campuses. 363 students at a private Illinois university completed an electronic survey regarding on-campus EC access (73.6% cisgender women, 52.

Bilateral Secondary Glaucoma Associated with Congenital Herpes Simplex Virus Keratitis: A Case Report and Review of the Literature.

Purpose: To highlight a relatively underappreciated yet significant complication of neonatal ocular herpes simplex virus (HSV) infection.

Methods: Observational case report of a 4-week-old patient with congenital ocular HSV infection over the course of 6-year follow-up.

Results: We describe a case of a neonate who developed bilateral HSV keratitis who subsequently developed bilateral glaucoma 9 months following primary infection.

Zeaxanthin augments CD8 effector T cell function and immunotherapy efficacy.

The detailed mechanisms underlying the regulatory significance of dietary components in modulating anti-tumor immunity remain largely unknown. Here, we apply a co-culture-based screening approach using a blood nutrient compound library and identify zeaxanthin (ZEA), a dietary carotenoid pigment found in many fruits and vegetables and known for its role in eye health, as an immunomodulator that enhances the cytotoxicity of CD8 T cells against tumor cells. Oral supplementation with ZEA, but not its structural isomer lutein (LUT), enhances anti-tumor immunity in vivo.

Proinflammatory Stress Activates Neutral Sphingomyelinase 2-Based Generation of a Ceramide-Enriched β-Cell EV Subpopulation.

Mechanisms connecting β-cell stress to extracellular vesicle (EV) cargo and diabetes are poorly defined. Does β-cell inflammatory stress engage neutral sphingomyelinase 2 (nSMase2)-dependent EV formation to generate ceramide-enriched small EVs? Proinflammatory cytokines increased β-cell small EV ceramide via increases in nSMase2. Ceramide-enriched EVs housed distinct cargo linked to insulin signaling, and ceramide species were enriched in plasma EVs from individuals with type 1 diabetes.

Downsizing Lactams via Rh-Catalyzed C-C Activation.

Ring-contraction reactions are valuable transformations to access harder-to-synthesize smaller-sized rings from more available larger-sized precursors. Herein, we report an unprecedented lactam downsizing strategy by taking advantage of removable directing groups (DGs) and Rh-catalyzed C-C activation. An efficient method for DG installation to common lactam substrates is developed by employing silylated amines and Ti catalysts, and the resulting amidine moiety can be converted back to lactams via acid-mediated hydrolysis.

The temperate coral maintains acid-base homeostasis through heat stress.

Heat stress can disrupt acid-base homeostasis in reef-building corals and other tropical cnidarians, often leading to cellular acidosis that can undermine organismal function. Temperate cnidarians experience a high degree of seasonal temperature variability, leading us to hypothesize that temperate taxa have more thermally robust pH homeostasis than their tropical relatives. To test this, we investigated how elevated temperature affects intracellular pH and calcification in the temperate coral .

Item-based Parsing of Dynamic Scenes in a Combined Attentional Tracking and Working Memory Task.

Human visual processing is limited-we can only track a few moving objects at a time and store a few items in visual working memory (WM). A shared mechanism that may underlie these performance limits is how the visual system parses a scene into representational units. In the present study, we explored whether multiple-object tracking (MOT) and WM rely on a common item-based indexing mechanism.

Robotic single-port femoral artery dissection and anastomosis with the da Vinci system: a cadaveric feasibility study.

Vascular surgical site infections (SSI) are common and associated with graft infection, surgical reintervention, and increased lengths of stay. While antibiotic prophylaxis and negative pressure dressings have improved SSI rates, reported incidence remains as high as 30%. Robotic approaches have decreased surgical site infections in multiple surgical specialties, but remain without a vascular surgery indication.

Refracting Blame in the Fentanyl Era: The Narrative Battleground on Facebook and Instagram.

: More than 80,000 Americans died of drug overdoses between August 2022 and August 2023, a crisis most recently driven by synthetic opioids like fentanyl. To investigate how blame for the opioid crisis is constructed within the most engaging content on Facebook and Instagram by identifying the dominant thematic frames and patterns of blame attribution. Using CrowdTangle, we collected US opioid-related posts from July 2022 to June 2023 and analyzed the top 0.

Durvalumab Plus Platinum-Etoposide in Extensive-Stage Small-Cell Lung Cancer: Outcomes in Age, Sex, and Platinum Subgroups From the Phase 3 CASPIAN Study.

Introduction: In the phase 3 CASPIAN study, first-line durvalumab plus etoposide combined with either carboplatin or cisplatin (EP) significantly improved overall survival (OS) versus EP alone in treatment-naïve extensive-stage small-cell lung cancer (ES-SCLC). We report exploratory subgroup analyses from CASPIAN.

Methods: Patients with untreated ES-SCLC were randomized to durvalumab plus EP or EP alone.

COVID-19 prevention behaviors are congruent within social networks of disenfranchised Hispanic and criminal legal involved community members.

Unlabelled: The COVID-19 (COVID) pandemic has had a disproportionate impact on people who have low income and identify as Hispanic or Latinx (PLIH) as well as those with criminal Legal Involvement (CLI). These two groups, and their intersection, are often disenfranchised from livable wage employment, basic social services, and healthcare, which are vital to prevent the spread of COVID. We examined baseline data from the Community Network-Driven COVID Testing of Marginalized Population in the Central US (C3) which included 1036 participants: 32.