The role of the Mediterranean diet in reducing the risk of cognitive impairement, dementia, and Alzheimer's disease: a meta-analysis.

Age-related cognitive impairment and dementia pose a significant global health, social, and economic challenge. While Alzheimer's disease (AD) has historically been viewed as the leading cause of dementia, recent evidence reveals the considerable impact of vascular cognitive impairment and dementia (VCID), which now accounts for nearly half of all dementia cases. The Mediterranean diet-characterized by high consumption of fruits, vegetables, whole grains, fish, and olive oil-has been widely recognized for its cardiovascular benefits and may also reduce the risk of cognitive decline and dementia.

Defining Mechanistic Links Between the Non-Coding Variant rs17673553 in and Lupus Susceptibility.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by widespread inflammation and autoantibody production. Its development and progression involve genetic, epigenetic, and environmental factors. Although genome-wide association studies (GWAS) have repeatedly identified a susceptibility signal at 16p13, its fine-scale source and its functional and mechanistic role in SLE remain unclear.

Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial.

Combined immune checkpoint blockade (ICB) and chemoradiation (CRT) is approved in patients with locally advanced cervical cancer (LACC) but optimal sequencing of CRT and ICB is unknown. NRG-GY017 (NCT03738228) was a randomized phase I trial of atezolizumab (anti-PD-L1) neoadjuvant and concurrent with CRT (Arm A) vs. concurrent with CRT (Arm B) in patients with high-risk node-positive LACC.

Pharmacological reduction of lipid hydroperoxides as a potential modulator of sarcopenia.

We previously reported that elevated expression of phospholipid hydroperoxide glutathione peroxidase 4, an enzyme that regulates membrane lipid hydroperoxides, can mitigate sarcopenia in mice. However, it is still unknown whether a pharmacological intervention designed to modulate lipid hydroperoxides might be an effective strategy to reduce sarcopenia in aged mice. Here we asked whether a newly developed compound, CMD-35647 (CMD), can reduce muscle atrophy induced by sciatic nerve transection.

Siah2 antagonism of Pard3/JamC modulates Ntn1-Dcc signaling to regulate cerebellar granule neuron germinal zone exit.

Exiting a germinal zone (GZ) initiates a cascade of events that promote neuronal maturation and circuit assembly. Developing neurons and their progenitors must interpret various niche signals-such as morphogens, guidance molecules, extracellular matrix components, and adhesive cues-to navigate this region. How differentiating neurons in mouse brains integrate and adapt to multiple cell-extrinsic niche cues with their cell-intrinsic machinery in exiting a GZ is unknown.

Differing Effects of Alcohol Use on Epigenetic and Brain Age in Adult Children of Parents with Alcohol Use Disorder.

Background: It is known that being the adult child of a parent with an alcohol use disorder (ACoA) can confer a wide variety of increased health and psychological risks, including higher rates of anxiety, depression, and post-traumatic stress disorder symptoms. Additionally, ACoAs are at greater risk of developing alcohol/substance use disorders (AUDs/SUDs) than individuals from families without a history of AUDs.

Methods: ACoA individuals with risky hazardous alcohol use ( = 14) and those not engaged in hazardous use ( = 14) were compared to a group of healthy controls.

COVID-19 Exacerbates Neurovascular Uncoupling and Contributes to Endothelial Dysfunction in Patients with Mild Cognitive Impairment.

Mild cognitive impairment (MCI) affects nearly 20% of older adults worldwide, with no targetable interventions for prevention. COVID-19 adversely affects cognition, with >70% of older adults with Long COVID presenting with cognitive complaints. Neurovascular coupling (NVC), an essential mechanism of cognitive function, declines with aging and is further attenuated in neurocognitive disorders.

Incorporating immune checkpoint inhibitors in epithelial ovarian cancer.

Objective: Therapeutic interventions for epithelial ovarian cancer (EOC) have increased greatly over the last decade but improvements outside of biomarker selected therapies have been limited. There remains a pressing need for more effective treatment options that can prolong survival and enhance the quality of life of patients with EOC. In contrast to the significant benefits of immunotherapy with immune checkpoint inhibitors (CPI) seen in many solid tumors, initial experience in EOC suggests limited efficacy of CPIs monotherapy.

Mechanistic studies of PFKFB2 reveals a novel inhibitor of its kinase activity.

The 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB) family of proteins are bifunctional enzymes that are of clinical relevance because of their roles in regulating glycolysis in insulin sensitive tissues and cancer. Here, we sought to express recombinant PFKFB2 and develop a robust protocol to measure its kinase activity. These studies resulted in the unexpected finding that bacterially expressed PFKFB2 is phosphorylated on Ser483 but is not a result of autophosphorylation.

Whole genome sequence-based association analysis of African American individuals with bipolar disorder and schizophrenia.

In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole genome sequencing of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study).

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Pulmonary neuroendocrine neoplasms: the molecular landscape, therapeutic challenges, and diagnosis and management strategies.

Lung neuroendocrine neoplasms are a group of diverse, heterogeneous tumours that range from well-differentiated, low-grade neuroendocrine tumours-such as typical and atypical carcinoids-to high-grade, poorly differentiated aggressive malignancies, such as large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC). While the incidence of SCLC has decreased, the worldwide incidence of other pulmonary neuroendocrine neoplasms has been increasing over the past decades. In addition to the standard histopathological classification of lung neuroendocrine neoplasms, the introduction of molecular and sequencing techniques has led to new advances in understanding the biology of these diseases and might influence future classifications and staging that can subsequently improve management guidelines in the adjuvant or metastatic settings.

Analysis of nuclear receptor expression in head and neck cancer.

Objective: Studies of squamous cell carcinoma of the head and neck (HNSCC) have demonstrated the importance of nuclear receptors and their associated coregulators in the development and treatment of HNSCC. We sought to characterize members of the nuclear receptor super family through interrogation of RNA-Seq and microarray data.

Materials And Methods: TCGA RNA-Seq data within the cBioportal platform comparing HNSCC samples (n = 515 patients with RNA-Seq data) to normal tissue (n = 82 patients) was interrogated for significant differences in nuclear receptor expression.

Guidelines to Analyze ChIP-Seq Data: Journey Through QC and Analysis Considerations.

ChIP-Seq is used to study DNA-protein interactions, unraveling chromatin states and gene regulatory properties of transcription factors. ChIP-Seq involves immunoprecipitation followed by sequencing using Next-Generation sequencing approaches. The ENCODE consortium provides extensive guidelines for ChIP-Seq analysis.

Detecting early stages of Alzheimer's disease using a web-based cognitive battery.

Portable and efficient cognitive screening measures are needed to address the growing need for effective early detection of Alzheimer's disease. The Neurotrack Cognitive Battery (NCB) offers an appealing, web-based application that may be sensitive to early cognitive changes associated with Alzheimer's disease. The NCB contains measures that were conceptually derived from animal lesion studies.

Cancer-specific innate and adaptive immune rewiring drives resistance to PD-1 blockade in classic Hodgkin lymphoma.

Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4 T cells and additional MHC class I-independent immune effectors. Here, we utilize single-cell RNA sequencing and spatial analysis to define shared circulating and microenvironmental features of the immune response to PD-1 blockade in cHL.

What's Left of Moral Bioenhancement? Reviewing a 15-Year Debate.

Should we implement biomedical interventions like psychopharmaceuticals or brain stimulation that aim to improve morality in society? Since 2008, moral bioenhancement (MBE) has received considerable attention in bioethics, generating wide scholarly disagreement. However, reviews on the subject are few and either outdated or not structured in method. This paper addresses this gap by providing a scoping review of the last 15 years of debate on MBE (from 2008 to 2022).

Clinical response to neurofeedback in major depression relates to subtypes of whole-brain activation patterns during training.

Major Depressive Disorder (MDD) poses a significant public health challenge due to its high prevalence and the substantial burden it places on individuals and healthcare systems. Real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) shows promise as a treatment for this disorder, although its mechanisms of action remain unclear. This study investigated whole-brain response patterns during rtfMRI-NF training to explain interindividual variability in clinical efficacy in MDD.

The physicochemical properties of lipopolysaccharide chemotypes regulate activation of the contact pathway of blood coagulation.

Lipopolysaccharide (LPS) is the primary pathogenic factor in Gram-negative sepsis. While the presence of LPS in the bloodstream during infection is associated with disseminated intravascular coagulation, the mechanistic link between LPS and blood coagulation activation remains ill-defined. The contact pathway of coagulation-a series of biochemical reactions that initiates blood clotting when plasma factors XII (FXII) and XI (FXI), prekallikrein (PK), and high molecular weight kininogen interact with anionic surfaces-has been shown to be activated in Gram-negative septic patients.

The expanding roles of myonuclei in adult skeletal muscle health and function.

Skeletal muscle cells (myofibers) require multiple nuclei to support a cytoplasmic volume that is larger than other mononuclear cell types. It is dogmatic that mammalian resident myonuclei rely on stem cells (specifically satellite cells) for adding new DNA to muscle fibers to facilitate cytoplasmic expansion that occurs during muscle growth. In this review, we discuss the relationship between cell size and supporting genetic material.

Consensus Recommendations for Studies of Outflow Facility and Intraocular Pressure Regulation Using Ex Vivo Perfusion Approaches.

Intraocular pressure (IOP) elevation is the primary risk factor and currently the main treatable factor for progression of glaucomatous optic neuropathy. In addition to direct clinical and living animal in vivo studies, ex vivo perfusion of anterior segments and whole eyes is a key technique for studying conventional outflow function as it is responsible for IOP regulation. We present well-tested experimental details, protocols, considerations, advantages, and limitations of several ex vivo model systems for studying IOP regulation.

Differential Infiltration of Key Immune T-Cell Populations Across Malignancies Varying by Immunogenic Potential and the Likelihood of Response to Immunotherapy.

Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers.

Origin of Chromosome 12 Trisomy Surge in Human Induced Pluripotent Stem Cells (iPSCs).

Cultured pluripotent stem cells are unique in being the only fully diploid immortal human cell lines. However, during continued culture they can acquire significant chromosome abnormalities. Chromosome 12 trisomy is the most common whole-chromosome abnormality found during culture of human induced pluripotent stem cells (iPSCs).