Mechanisms of immunotherapy resistance in small cell lung cancer.

Small-cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with a poor prognosis. Although the addition of immunotherapy to chemotherapy has modestly improved outcomes, most patients rapidly develop resistance. Resistance to immunotherapy can be broadly categorized into primary resistance and acquired resistance, as proposed by the Society for Immunotherapy of Cancer (SITC) consensus definition.

Evolving trends in novel sleep tracking and sleep testing technology publications between 2020-2022.

Study Objectives: To update sleep medicine providers regarding (1) published research on the uses and performance of novel sleep tracking and testing technologies (2) the use of artificial intelligence to acquire and process sleep data and (3) research trends and gaps regarding the development and/or evaluation of these technologies.

Methods: Medline and Embase electronic databases were searched for studies utilizing screening and diagnostic sleep technologies, published between 2020 and 2022 in journals focusing on human sleep. Studies' quality was determined based on the Study Design criteria of The Oxford Centre for Evidence-Based Medicine Levels of Evidence.

Phase 2 Open-Label Study of Sacituzumab Govitecan as Second-Line Therapy in Patients With Extensive-Stage Small Cell Lung Cancer: Results From TROPiCS-03.

Introduction: The phase 2 TROPiCS-03 study evaluated the efficacy/safety of sacituzumab govitecan (SG) as second-line treatment in patients with previously treated extensive-stage small cell lung cancer (ES-SCLC).

Methods: TROPiCS-03 (NCT03964727) is a multicohort, open-label, phase 2 basket study in solid tumors, including ES-SCLC. Adults with ES-SCLC that progressed after one prior line of platinum-based chemotherapy and anti-programmed death-(ligand) 1 (PD-[L]1) therapy received SG 10 mg/kg on days 1 and 8 of a 21-day cycle.

Assessing asymmetric enhancement on breast MRI: Besting the diagnostic challenge with imaging and clinical clues.

Breast magnetic resonance imaging (MRI) has the highest sensitivity for breast cancer detection compared to other breast imaging modalities such as mammography and ultrasound. As a functional modality, it captures the increased angiogenic activity of breast cancer through gadolinium-based contrast enhancement. Normal breast tissue also enhances, albeit in distinct patterns termed background parenchymal enhancement (BPE).

Pathobiont-driven antibody sialylation through IL-10 undermines vaccination.

The pathobiont Staphylococcus aureus (Sa) induces nonprotective antibody imprints that underlie ineffective staphylococcal vaccination. However, the mechanism by which Sa modifies antibody activity is not clear. Herein, we demonstrate that IL-10 is the decisive factor that abrogates antibody protection in mice.

A 5-day course of repetitive transcranial magnetic stimulation before pain onset ameliorates future pain and increases sensorimotor peak alpha frequency.

Repetitive transcranial magnetic stimulation (rTMS) has shown promise as an intervention for pain. An unexplored research question is whether the delivery of rTMS prior to pain onset might protect against a future episode of prolonged pain. The present study aimed to determine whether (1) 5 consecutive days of rTMS delivered prior to experimentally induced prolonged jaw pain has a prophylactic effect on future pain intensity and (2) whether these effects were accompanied by increases in corticomotor excitability (CME) and/or sensorimotor peak alpha frequency (PAF).

Eosinophilic esophagitis drives tissue fibroblast regenerative programs toward pathologic dysfunction.

Background: Pathologic tissue remodeling with scarring and tissue rigidity has been demonstrated in inflammatory, autoimmune, and allergic diseases. Eosinophilic esophagitis (EoE) is an allergic disease that is diagnosed and managed by repeated biopsy procurement, allowing an understanding of tissue fibroblast dysfunction. While EoE-associated tissue remodeling causes clinical dysphagia, food impactions, esophageal rigidity, and strictures, molecular mechanisms driving these complications remain under investigation.

Prevention and Treatment of Cancer-Related Infections, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

There is an increased risk of infection in patients with cancer that results in higher morbidity and mortality. Several risk factors can predispose these patients to infectious complications. Some such factors include immunocompromised states like neutropenia, allogeneic hematopoietic cell transplantation, and graft-versus-host disease, while others include immunosuppressive agents like corticosteroids, purine analogs, monoclonal antibodies, and other emerging cancer therapeutics like CAR T-cell therapy.

Update on MR Imaging Techniques of the Hip.

MR imaging protocols and technical parameters should be optimized in order to achieve the best diagnostic results. Routine hip MR imaging includes a combination of T1-weighted and fluid-sensitive sequences, obtained in coronal, axial, and sagittal planes. MR arthrography of the hip can be used for assessment of intra-articular pathology involving intricate and signal-poor structures such as articular cartilage, labral fibrocartilage, and intra-articular bodies.

Evaluating the Impact of a Game (Inner Dragon) on User Engagement Within a Leading Smartphone App for Smoking Cessation: Randomized Controlled Trial.

Background: Smartphone apps are a convenient, low-cost approach to delivering smoking cessation support to large numbers of individuals. Yet, the apps are susceptible to low rates of user engagement and retention.

Objective: This study aims to test the effects of a new game module (called Inner Dragon) integrated into Smoke Free (23 Limited), a leading smoking cessation app with established efficacy.

Developmental Social Experience Changes Behavior in a Threatening Environment in Catfish.

Coordinated responses to threats are important for predator evasion in many species. This study examines the effect of developmental social experience on antipredator behavior and group cohesion in a highly gregarious catfish that communicates via tactile interaction, We reared fish either in a mixed-age group of age-matched peers and adult (mixed-age condition, or MAC), or with age-matched peers only (same-age condition, or SAC). A startle test was conducted with small groups of subadults from either social rearing condition.

Exploration of Glycosyl Dithioimidocarbonates in Photoinduced Desulfurative Cross-Coupling Reactions.

Readily synthesized bench-stable glycosyl dithioimidocarbonates are useful -glycoside precursors. Under mild photochemical conditions, these glycosides undergo desulfurative glycosyl radical generation in the presence of weak acid, 4CzIPN, and Hantzsch ester. These radicals perform well in Geise-like reactions to yield -glycosides with high stereoselectivity.

The association of increased SNAP benefits during COVID-19 with food insufficiency and anxiety among US adults: a quasi-experimental study.

Objectives: The COVID-19 pandemic and subsequent policy response to mitigate disease spread had far-reaching impacts on health and social well-being. In response, the Supplemental Nutrition Assistance Program (SNAP) underwent several pandemic-era modifications, including a 15 % monthly benefit increase on January 1, 2021. Research documenting the health effects of these SNAP modifications among low-income households and minoritized groups who were most impacted by the economic fallout during the first years of the pandemic is lacking.

Combination of bortezomib and venetoclax targets the pro-survival function of LMP-1 and EBNA-3C of Epstein-Barr virus in spontaneous lymphoblastoid cell lines.

Epstein-Barr virus (EBV) manipulates the ubiquitin-proteasome system and regulators of Bcl-2 family to enable the persistence of the virus and survival of the host cells through the expression of viral proteins in distinct latency patterns. We postulate that the combination of bortezomib (proteasome inhibitor) and venetoclax (Bcl-2 inhibitor) [bort/venetoclax] will cause synergistic killing of post-transplant lymphoproliferative disorder (PTLD) through targeting the pro-survival function of latent viral proteins such as latent membrane protein-1 (LMP-1) and EBV nuclear antigen-3C (EBNA-3C). Bort/venetoclax could synergistically kill spontaneous lymphoblastoid cell lines (sLCLs) derived from patients with PTLD and EBV-associated hemophagocytic lymphohistiocytosis by inducing DNA damage response, apoptosis and G1-S cell cycle arrest in a ROS-dependent manner.

The human milk oligosaccharide 3'sialyllactose reduces low-grade inflammation and atherosclerosis development in mice.

Macrophages contribute to the induction and resolution of inflammation and play a central role in chronic low-grade inflammation in cardiovascular diseases caused by atherosclerosis. Human milk oligosaccharides (HMOs) are complex unconjugated glycans unique to human milk that benefit infant health and act as innate immune modulators. Here, we identify the HMO 3'sialyllactose (3'SL) as a natural inhibitor of TLR4-induced low-grade inflammation in macrophages and endothelium.

A Phase I First-in-Human Study of ABBV-011, a Seizure-Related Homolog Protein 6-Targeting Antibody-Drug Conjugate, in Patients with Small Cell Lung Cancer.

Purpose: Seizure-related homolog protein 6 (SEZ6) is a novel target expressed in small cell lung cancer (SCLC). ABBV-011, a SEZ6-targeted antibody conjugated to calicheamicin, was evaluated in a phase I study (NCT03639194) in patients with relapsed/refractory SCLC. We report initial outcomes of ABBV-011 monotherapy.

Design of linked-domain protein inhibitors of UBE2D as tools to study cellular ubiquitination.

Ubiquitin (Ub) is a post-translational modification that largely controls proteostasis through mechanisms spanning transcription, translation, and notably, protein degradation. Ub conjugation occurs through a hierarchical cascade of three enzyme classes (E1, E2, and E3s) involving >1000 proteins that regulate the ubiquitination of proteins. The E2 Ub-conjugating enzymes are the midpoint, yet their cellular roles remain under-characterized, partly due to a lack of inhibitors.

The Epstein-Barr Virus Nuclear Antigen 1 Variant Associated with Nasopharyngeal Carcinoma Defines the Sequence Criteria for Serologic Risk Prediction.

Purpose: Antibodies to select Epstein-Barr virus proteins can diagnose early-stage nasopharyngeal carcinoma (NPC). We have previously shown that IgA against Epstein-Barr virus nuclear antigen 1 (EBNA1) can predict incident NPC in high- and intermediate-risk cohorts 4 years before diagnosis. Here, we tested EBNA1 variants, with mutants, to define the sequence requirements for an NPC risk assay.

Cellular processing of beneficial emerging proteins.

Novel proteins can originate from non-coding DNA and contribute to species-specific adaptations. It is challenging to conceive how emerging proteins may integrate pre-existing cellular systems to bring about beneficial traits, given that their sequences are previously unseen by the cell. To address this apparent paradox, we investigated 26 emerging proteins previously associated with growth benefits in yeast.

Comprehensive Husbandry Protocol for Catfish and Many Other Amazonian Species.

A variety of fish species have proven instrumental in the investigation of evolution, behavior, ecology, and physiology, among many other fields. Many model systems (e.g.

The reliability and validity of rapid transcranial magnetic stimulation mapping for muscles under active contraction.

Rapid mapping is a transcranial magnetic stimulation (TMS) mapping method which can significantly reduce data collection time compared to traditional approaches. However, its validity and reliability has only been established for upper-limb muscles during resting-state activity. Here, we determined the validity and reliability of rapid mapping for non-upper limb muscles that require active contraction during TMS: the masseter and quadriceps muscles.