Interferon-ε loss is elusive 9p21 link to immune-cold tumors, resistant to immune-checkpoint therapy and endogenous CXCL9/10 induction.

Introduction: Copy-number (CN) loss of chromosome 9p, or parts thereof, impair immune response and confer ICT resistance by direct elimination of immune-regulatory genes on this arm, notably IFNγ genes at 9p24.1, and type-I interferon (IFN-I) genes at 9p21.3.

Effectiveness of sequential bilateral repetitive transcranial stimulation versus bilateral theta burst stimulation for patients with treatment-resistant depression (BEAT-D): a randomized non-inferiority clinical trial.

Background: Bilateral repetitive transcranial magnetic stimulation (BL-rTMS) over the dorsolateral prefrontal cortex is effective for treatment-resistant depression (TRD). Owing to a shorter treatment time, bilateral theta burst stimulation (BL-TBS) can be more efficient protocol. The non-inferiority of BL-TBS to BL-rTMS was established in late-life TRD; however, this has not been determined in adults of other age groups.

Stroke Volume Augmentation Improves with PH-Targeted Therapy in Patients with Exercise-Induced Pulmonary Hypertension.

Unlabelled: Exercise-induced pulmonary arterial hypertension (EiPH) is often treated with off-label use of pulmonary arterial hypertension-targeted therapy (PH-targeted therapy). Most measures of PAH severity are normal in patients with EiPH, posing challenges in evaluating for physiological improvement in patients treated for EiPH. In this study, we used non-invasive cardiopulmonary exercise testing (CPET) to assess for objective improvement in patients treated for EiPH.

Dulce Digital-Me: results of a randomized comparative trial of static versus adaptive digital interventions for Latine adults with diabetes.

Objective: To compare the effectiveness of a static, text-based diabetes education and support intervention (Dulce Digital, DD) versus a dynamic approach with personalized feedback and goal setting (Dulce Digital-Me, DD-Me) in improving diabetes outcomes.

Design And Methods: Comparative effectiveness trial in 310 Latine adults with poorly managed type 2 diabetes in a Federally Qualified Health Center in Southern California, randomized to DD, DD-Me-Auto (algorithm-driven text-based personalized feedback), or DD-Me-Tel (coach delivered personalized feedback). Changes in HbA1c (primary outcome), low-density lipoprotein-cholesterol, systolic blood pressure, and patient-reported outcomes were examined across 6 and 12 months, with the primary comparison being DD versus DD-Me (combined automated and telephonic).

Missense Mutations of the Ephrin Receptor EPHA1 Associated with Alzheimer's Disease Disrupt Receptor Signaling Functions.

Missense mutations in the EPHA1 receptor tyrosine kinase have been identified in Alzheimer's patients. To gain insight into their potential role in disease pathogenesis, we investigated the effects of four of these mutations. We show that the P460L mutation in the second fibronectin type III (FN2) domain drastically reduces EPHA1 cell surface localization while increasing tyrosine phosphorylation of the cell surface localized receptor.

Mapping the FGF2 Interactome Identifies a Functional Proteoglycan Coreceptor.

Fibroblast growth factor 2 (FGF2) is a multipotent growth factor and signaling protein that exhibits broad functions across multiple cell types. These functions are often initiated by binding to growth factor receptors and fine-tuned by glycosaminoglycan (GAG)-modified proteins called proteoglycans. The various outputs of FGF2 signaling and functions arise from a dynamic and cell type-specific set of binding partners.

Co-immunization with spike and nucleocapsid based DNA vaccines for long-term protective immunity against SARS-CoV-2 Omicron.

The continuing evolution of SARS-CoV-2 variants challenges the durability of existing spike (S)-based COVID-19 vaccines. We hypothesized that vaccines composed of both S and nucleocapsid (N) antigens would increase the durability of protection by strengthening and broadening cellular immunity compared with S-based vaccines. To test this, we examined the immunogenicity and efficacy of wild-type SARS-CoV-2 S- and N-based DNA vaccines administered individually or together to K18-hACE2 mice.

An Improved P(V) Thio-Oligonucleotide Synthesis Platform.

Three critical advances in simplifying the adoption of P(V)-based stereopure, phosphorothioate-containing oligonucleotide synthesis are reported. A more inexpensive phosphorus-sulfur incorporation reagent () is introduced, a robust linker system was developed, and a systematic study of common nucleobase protecting groups was performed to significantly reduce the barrier to adoption of this technology.

Evidence for the importance of trophically transmitted parasites and predation at the lower latitudes of species ranges.

The lack of information concerning how parasitism maps onto host geographical distributions represents a striking gap in ecological knowledge. This knowledge gap limits our understanding of a wide range of phenomena, including the consequences of climate change-induced range shifts of both hosts and parasites. To help solve this problem, we created a predictive theoretical framework and quantified latitudinal variation in parasitism by animal and protozoan parasites throughout the entire contiguous geographical ranges of four estuarine fish species.

Assessing the effects of Enhanced Multicomponent Proactive Navigator-Assisted Cessation of Tobacco Use within a federally qualified health center (EMPACT-Us): a protocol study.

Background: California's relatively low smoking rate (10.1% in 2019-2020) (About CHIS, UCLA Center for Health Policy Research, 2024) masks deep disparities among low-income populations, where smoking rates are nearly double that of their middle- to upper-income peers. Low-income smokers report a similar desire to quit and similar rates of recent quit attempts as smokers from other groups; yet, they often face barriers in accessing effective resources to facilitate successful cessation.

Contrasteric Glycosylations of Cotylenol and 1,2-Diols by Virtual Linker Selection.

Many terpene glycosides exhibit contrasteric patterns of 1,2-diol glycosylation in which the more hindered alcohol bears a sugar; protection of the less hindered alcohol only increases steric repulsion. Here, we report a method for contrasteric glycosylation using a new sugar-linker that forms a cleavable, 10-membered ring with high efficiency, leading to syntheses of cotylenin E, J, and ISIR-050. Linker selection was aided by DFT calculations of side reactions and stereoselectivity, as well as conformational analyses using autoDFT, a Python script that converts SMILES strings to DFT-optimized conformational ensembles.

Palladium Bisphosphine Monoxide Complexes: Synthesis, Scope, Mechanism, and Catalytic Relevance.

Recent studies in transition metal catalysis employing chelating phosphines have suggested a role for partial ligand oxidation in formation of the catalytically active species, with potentially widespread relevance in a number of catalytic systems. We examine the internal redox reaction of Pd(bisphosphine)X (X = Cl, OAc, ) complexes to reveal previously underexplored aspects of bisphosphine monoxides (BPMOs), including evaluation of ligand structure and development of general reaction conditions to access a collection of structurally diverse BPMO precatalysts based on organopalladium oxidative addition complexes. In particular, a series of Pd(BPMO)(R)(X) (R = aryl, alkyl; X = I, Br) oxidative addition complexes bearing 24 different BPMO ligands were characterized by NMR and X-ray crystallography.

Tumor-Targeted Cell-Penetrating Peptides Reveal That Monomethyl Auristatin E Temporally Modulates the Tumor Immune Microenvironment.

Chemotherapies remain standard therapy for cancers but have limited efficacy and cause significant side effects, highlighting the need for targeted approaches. In the progression of cancer, tumors increase matrix metalloproteinase (MMP) activity. Leveraging and therapeutically redirecting tumor MMPs through activatable cell-penetrating peptide (ACPP) technology offers new approaches for tumor-selective drug delivery and for studying how drug payloads engage the tumor immune microenvironment.

Effectiveness and Safety of Irreversible Electroporation When Used for the Ablation of Stage 3 Pancreatic Adenocarcinoma: Initial Results from the DIRECT Registry Study.

Background/objectives: Overall survival for patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) remains limited, with a median survival of 12 to 15 months. Irreversible electroporation (IRE) is a local tumor ablation method that induces cancerous cell death by disrupting cell membrane homeostasis. The DIRECT Registry study was designed to assess the effectiveness and safety of IRE when combined with standard of care (SOC) treatment for Stage 3 PDAC versus SOC alone in a real-world setting after at least 3 months of induction chemotherapy; Methods: Patients with Stage 3 PDAC treated with IRE plus SOC or SOC alone were prospectively enrolled in a multicenter registry study.

Aspirin modulates generation of procoagulant phospholipids in cardiovascular disease, by regulating LPCAT3.

Background: Enzymatically oxygenated phospholipids (eoxPL) from lipoxygenases (LOX) or cyclooxygenase (COX) are pro-thrombotic. Their generation in arterial disease, and their modulation by cardiovascular therapies is unknown. Furthermore, the Lands cycle acyl-transferases that catalyze their formation are unidentified.

Lymphovascular Tumoral Emboli in Inflammatory Breast Cancer Result from Haptotaxis-Mediated Encircling Lymphangiogenesis.

Inflammatory breast cancer (IBC) is characterized by numerous tumor emboli within lymphatics. In a recent study, we observed tumor embolic budding both in vitro and in vivo within lymphovascular spaces and proposed this to account for the plethora of tumor emboli seen in IBC. These observations did not address, however, how lymphovascular invasion is initiated or the mechanisms involved.

Influence of Environmental Conditions on the Escape Rates of Biocontained Genetically Engineered Microbes.

The development of genetically engineered microbes (GEMs) has resulted in an urgent need to control their persistence in the environment. The use of biocontainment such as kill switches is a critical approach to prevent the unintended proliferation of GEMs; however, the effectiveness of kill switches─reported as escape rates, i.e.

ERBB2/ERBB3-mutated S100/SOX10-positive uterine sarcoma: something new.

A distinctive subset of uterine mesenchymal tumors display recurrent genetic fusions involving receptor tyrosine kinases, including NTRK, PDGFB, FGFR1, and RET, presumably leading to aberrant pathway activation. A pair of recent studies have highlighted the existence of a genetic fusion-negative uterine sarcoma that is characterized by activating mutations in ERBB2/ERBB3, CDKN2A deletion, inactivating ATRX mutation, and a S100 + /SOX10 + immunohistochemical profile. This report describes another case of this emerging entity that was diagnosed in a 57-year-old woman.

Social risk factors and cancer prevention care among patients in community health-care settings.

Background: Social risks are negatively associated with receipt of cancer preventive care. As knowledge is lacking on the pathways underlying these associations, we investigated associations between patient-reported social risks and colorectal cancer (CRC), cervical cancer, and breast cancer screening order provision and screening completion.

Methods: This study included patients eligible for CRC, cervical cancer, or breast cancer screening at 186 community-based clinics between July 1, 2015, and February 29, 2020.

Outcomes of Intranodal and Modified Intranodal Lymphangiography for Treatment of Traumatic Chylous Leaks in the Thorax and Neck.

Purpose: To report outcomes, procedure and fluoroscopy times, and adverse event rates after intranodal lymphangiography (IL) and modified IL (mIL) for treatment of traumatic chylous leaks in the thorax and neck.

Methods: Under an IRB-approved protocol, retrospective review of a quality assurance database identified all lymphangiograms for post-surgical refractory chylous leaks in the thorax and neck at a tertiary center from 2002-2022. Records were reviewed for technical and clinical outcomes, procedure and fluoroscopy times, and adverse events.

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

ClearDepth: a simple, robust, and low-cost method to assess root depth in soil.

Root depth is a major determinant of plant performance during drought and a key trait for strategies to improve soil carbon sequestration to mitigate climate change. While the model Arabidopsis thaliana offers numerous advantages for studies of root system architecture and root depth, its small and fragile roots severely limit the use of the methods and techniques currently available for such studies in soils. To overcome this, we have developed ClearDepth, a conceptually simple, non-destructive, sensitive, and low-cost method to estimate the root depth of Arabidopsis in relatively small pots that are amenable to mid- and large-scale studies.

Genome-based newborn screening for severe childhood genetic diseases has high positive predictive value and sensitivity in a NICU pilot trial.

Large prospective clinical trials are underway or planned that examine the clinical utility and cost effectiveness of genome-based newborn screening (gNBS). One gNBS platform, BeginNGS, currently screens 53,575 variants for 412 severe childhood genetic diseases with 1,603 efficacious therapies. Retrospective evaluation of BeginNGS in 618,290 subjects suggests adequate sensitivity and positive predictive value (PPV) to proceed to prospective studies.