Integrative genomic analysis of DLBCL identifies immune environments associated with bispecific antibody response.

Most diffuse large B-cell lymphoma (DLBCL) patients treated with immunotherapies such as bispecific antibodies (BsAb) or chimeric antigen receptor (CAR) T cells fail to achieve durable treatment responses, underscoring the need for a deeper understanding of mechanisms that regulate the immune environment and response to treatment. Here, an integrative, multi-omic approach was applied to multiple large independent datasets in order to characterize DLBCL immune environments, and to define their association with tumor cell-intrinsic genomic alterations and outcomes to CD19-directed CAR T-cell and CD20 x CD3 BsAb therapies. This approach effectively segregated DLBCLs into four immune quadrants (IQ) defined by cell-of-origin and immune-related gene set expression scores.

Rational Design of Nanozymes for Engineered Cascade Catalytic Cancer Therapy.

Nanozymes have shown significant potential in cancer catalytic therapy by strategically catalyzing tumor-associated substances and metabolites into toxic reactive oxygen species (ROS) , thereby inducing oxidative stress and promoting cancer cell death. However, within the complex tumor microenvironment (TME), the rational design of nanozymes and factors like activity, reaction substrates, and the TME itself significantly influence the efficiency of ROS generation. To address these limitations, recent research has focused on exploring the factors that affect activity and developing nanozyme-based cascade catalytic systems, which can trigger two or more cascade catalytic processes within tumors, thereby producing more therapeutic substances and achieving efficient and stable cancer therapy with minimal side effects.

Triatoma venosa and Panstrongylus geniculatus challenge the certification of interruption of vectorial Trypanosoma cruzi transmission by Rhodnius prolixus in eastern Colombia.

Reactivation of Trypanosoma cruzi transmission by native vectors with different domiciliation capabilities is a major concern for Chagas disease control programs. T. cruzi transmission via intra-domestic Rhodnius prolixus was certified as interrupted by the Pan American Health Organization in Miraflores municipality (Boyacá, Colombia) in 2019.

Intramolecular Fluoroacylation Enabled by TrBF-Catalyzed Fluoride Recycling.

Alkyne- and alkene-tethered acyl fluorides undergo intramolecular carbofluorination via fluoride recycling using catalytic TrBF. Excellent stereoselectivity is observed for the alkyne addition, enabling access to novel fluorinated indan-2-ones (all ≥95:5 /) and cyclopentan-2-ones (85:15 /). Fluorinated chroman-2-ones and tertiary alkyl fluorides can also be synthesized using this method, comparing favorably to previously reported protocols that employ expensive metal catalysts under harsher conditions.

Exploring van der Waals Cuprate Superconductors Using a Hybrid Microwave Circuit.

The advent of two-dimensional van der Waals materials is a frontier of condensed matter physics and quantum devices. However, characterizing such materials remains challenging due to the limitations of bulk material techniques, necessitating the development of specialized methods. Here, we investigate the superconducting properties of BiSrCaCuO flakes by integrating them with a hybrid superconducting microwave resonator.

Computational Modeling of Electrocatalysts for CO Reduction: Probing the Role of Primary, Secondary, and Outer Coordination Spheres.

ConspectusIn the search for efficient and selective electrocatalysts capable of converting greenhouse gases to value-added products, enzymes found in naturally existing bacteria provide the basis for most approaches toward electrocatalyst design. Ni,Fe-carbon monoxide dehydrogenase (Ni,Fe-CODH) is one such enzyme, with a nickel-iron-sulfur cluster named the C-cluster, where CO binds and is converted to CO at high rates near the thermodynamic potential. In this Account, we divide the enzyme's catalytic contributions into three categories based on location and function.

Reproductive Risk Estimation Calculator for Balanced Translocation Carriers: An Improved Web-based Resource for Medical Genetics Professionals.

Balanced translocation carriers experience elevated reproductive risks, including pregnancy loss and children with anomalies due to generating chromosomally unbalanced gametes. While understanding the likelihood of producing unbalanced conceptuses is critical for individuals to make reproductive decisions, risk estimates are difficult to obtain as most balanced translocations are unique. To improve reproductive risk estimates, Drs.

Mindful self-compassion for lung cancer (MSC-LC): Incorporating perspectives of lung cancer patients, clinicians, and researchers to create an adapted intervention to reduce lung cancer stigma.

Background: Stigma is a pervasive and distressing problem experienced frequently by lung cancer patients, and there is a lack of psychosocial interventions that target the reduction of lung cancer stigma. Mindful self-compassion (MSC) is an empirically supported intervention demonstrated to increase self-compassion and reduce feelings of shame and distress in non-cancer populations. However, there are several anticipated challenges for delivering MSC to lung cancer patients, and modifications may be needed to improve acceptability, appropriateness, and feasibility.

Exploring the role of T cells in Alzheimer's and other neurodegenerative diseases: Emerging therapeutic insights from the T Cells in the Brain symposium.

This proceedings article summarizes the inaugural "T Cells in the Brain" symposium held at Columbia University. Experts gathered to explore the role of T cells in neurodegenerative diseases. Key topics included characterization of antigen-specific immune responses, T cell receptor (TCR) repertoire, microbial etiology in Alzheimer's disease (AD), and microglia-T cell crosstalk, with a focus on how T cells affect neuroinflammation and AD biomarkers like amyloid beta and tau.

Disrupted Cross-Scale Network Associated With Cognitive-Emotional Disorders in Sudden Sensorineural Hearing Loss.

Background: Sudden sensorineural hearing loss (SSNHL) is associated with abnormal changes in the brain's central nervous system. Previous studies on the brain networks of SSNHL have primarily focused on functional connectivity within the brain. However, in addition to functional connectivity, structural connectivity also plays a crucial role in brain networks.

A neuropathology case report of a woman with Down syndrome who remained cognitively stable: Implications for resilience to neuropathology.

Introduction: Aging adults with Down syndrome (DS) accumulate Alzheimer's disease (AD) neuropathology, including amyloid beta plaques and neurofibrillary tangles, by age 40.

Methods: We present findings from an individual with DS who remained cognitively stable despite AD neuropathology. Clinical assessments, fluid biomarkers, neuroimaging, and neuropathological examinations were conducted to characterize her condition.

Chromosome-level assembly of basil genome unveils the genetic variation driving Genovese and Thai aroma types.

Basil, Ocimum basilicum L., is a widely cultivated aromatic herb, prized for its culinary and medicinal uses, predominantly owing to its unique aroma, primarily determined by eugenol for Genovese cultivars or methyl chavicol for Thai cultivars. To date, a comprehensive basil reference genome has been lacking, with only a fragmented draft available.

Forensic Assessment of Kinship, Genomic Ancestry, and Natural History of an Iconic Tiger of Harlem-New York City.

In the fall of 2003, a two-year-old tiger named Ming, weighing some four hundred pounds, was discovered living in an apartment in Harlem, New York. Ming's rescue by NYPD was witnessed, recalled, and venerated by scores of neighbors. The tiger's history and ancestry stimulated considerable media interest, investigative sleuthing, and forensic genomic analyses.

Four targets: an enhanced framework for guiding causal inference from observational data.

Observational studies play an increasingly important role in estimating causal effects of a treatment or an exposure, especially with the growing availability of routinely collected real-world data. To facilitate drawing causal inference from observational data, we introduce a conceptual framework centered around "four targets"-target estimand, target population, target trial, and target validity. We illustrate the utility of our proposed "four targets" framework with the example of buprenorphine dosing for treating opioid use disorder, explaining the rationale and process for employing the framework to guide causal thinking from observational data.

Multi-center benchmarking of cervical spinal cord RF coils for 7 T MRI: A traveling spines study.

Purpose: The depth within the body, small diameter, long length, and varying tissue surrounding the spinal cord impose specific considerations when designing radiofrequency coils. The optimal coil configuration for 7 T cervical spinal cord MRI is unknown and, currently, there are very few coil options. The purpose of this work was (1) to establish a quality control protocol for evaluating 7 T cervical spinal cord coils and (2) to use that protocol to evaluate the performance of 4 different coil designs.

A preparatory cranial potential for saccadic eye movements in macaque monkeys.

Response preparation is accomplished by gradual accumulation in neural activity until a threshold is reached. In humans, such a preparatory signal, referred to as the lateralized readiness potential, can be observed in the EEG over sensorimotor cortical areas before execution of a voluntary movement. Although well-described for manual movements, less is known about preparatory EEG potentials for saccadic eye movements in humans and nonhuman primates.

Distinct CD8 T-cell types Associated with COVID-19 Severity in Unvaccinated HLA-A2 Patients.

Although emerging data have revealed the critical role of memory CD8 T cells in preventing and controlling SARS-CoV-2 infection, virus-specific CD8 T-cell responses against SARS-CoV-2 and its memory and innate-like subsets in unvaccinated COVID-19 patients with various disease manifestations in an HLA-restricted fashion remain to be understood. Here, we show the strong association of protective cellular immunity with mild COVID-19 and unique cell types against SARS-CoV-2 virus in an HLA-A2 restricted manner. ELISpot assays reveal that SARS-CoV-2-specific CD8 T-cell responses in mild COVID-19 patients are significantly higher than in severe patients, whereas neutralizing antibody responses against SARS-CoV-2 virus significantly correlate with disease severity.

Mid-trimester resolution of marked dextroposition of the fetal heart preceding regression of extensive left fetal lung lesion consisting of hybrid congenital pulmonary airway malformation (CPAM) and bronchopulmonary sequestration (BPS).

Extensive congenital pulmonary airway malformation (CPAM) of the left fetal lung and associated marked dextroposition of the fetal heart were noted at 21 weeks' gestation. The right fetal lung appeared compressed with the cardiomediastinal shift angle measuring approximately 20 degrees. Potential subsequent right pulmonary hypoplasia was considered.

Association of a multiplex immune marker panel with incident cognitive impairment and dementia: The Northern Manhattan Study.

Objective: To determine whether a panel of immune markers adds significant information to known correlates of risk of dementia and cognitive impairment.

Background: The impact of immune mechanisms on dementia risk is incompletely characterized.

Design/methods: A subsample of the Northern Manhattan Study, a prospective cohort study in the racially/ethnically diverse population of New York City, underwent comprehensive neuropsychological testing up to three times, at approximately 5-year intervals.

After-hours, Severity, and Distance are Associated with Non-VHA Emergency Department Use for Older Veterans: Insights from a Regional Health Information Exchange.

Background: Older adults treated in emergency departments (EDs) are at higher risk for adverse outcomes. Using multiple facilities can worsen this issue through service duplication and poor care transitions. Veterans with dual insurance coverage can access both Veterans Health Administration (VHA) and non-VHA EDs.

Improving auditory attention decoding by classifying intracranial responses to glimpsed and masked acoustic events.

Listeners with hearing loss have trouble following a conversation in multitalker environments. While modern hearing aids can generally amplify speech, these devices are unable to tune into a target speaker without first knowing to which speaker a user aims to attend. Brain-controlled hearing aids have been proposed using auditory attention decoding (AAD) methods, but current methods use the same model to compare the speech stimulus and neural response, regardless of the dynamic overlap between talkers which is known to influence neural encoding.

Lazertinib: breaking the mold of third-generation EGFR inhibitors.

Small molecules targeting activating mutations within the epidermal growth factor receptor (EGFR) are efficacious anticancer agents, particularly in non-small cell lung cancer (NSCLC). Among these, lazertinib, a third-generation tyrosine kinase inhibitor (TKI), has recently gained FDA approval for use in combination with amivantamab, a dual EGFR/MET-targeting monoclonal antibody. This review delves into the discovery and development of lazertinib underscoring the improvements in medicinal chemistry properties, especially in comparison with osimertinib.