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.

Exploration of degrons and their ability to mediate targeted protein degradation.

Degrons are short amino acid sequences that can facilitate the degradation of protein substrates. They can be classified as either ubiquitin-dependent or -independent based on their interactions with the ubiquitin proteasome system (UPS). These amino acid sequences are often found in exposed regions of proteins serving as either a tethering point for an interaction with an E3 ligase or initiating signaling for the direct degradation of the protein.

A mixed-methods investigation of a digital mental health tool to manage posttrauma anger.

Problematic anger affects up to 30% of individuals who have experienced trauma. Digital mental health approaches, such as ecological momentary assessment (EMA) delivered via smartphone and wearable devices (i.e.

Improving Cooking Skills, Lifestyle Behaviors, and Clinical Outcomes for Adults at Risk for Cardiometabolic Disease: Protocol for a Randomized Teaching Kitchen Multisite Trial (TK-MT).

Background/objectives: This protocol describes a study to investigate the feasibility and preliminary efficacy of a novel Teaching Kitchen Multisite Trial (TK-MT) for adults with cardiometabolic abnormalities. The TK-MT protocol describes a hybrid lifestyle intervention combining in-person and virtual instruction in culinary skills, nutrition education, movement, and mindfulness with community support and behavior change strategies. This 18-month-long randomized controlled trial aims to evaluate the feasibility of implementing a 12-month, 24 class program, assess preliminary study efficacy, and identify barriers and facilitators to implementation.

Influence of Aging and Immune Alterations on Susceptibility to Pneumococcal Pneumonia in the Elderly.

Pneumonia is a common respiratory infection affecting individuals of all ages, with a significantly higher incidence among the elderly. As the aging population grows, pneumonia is expected to become an increasingly critical health concern. In non-institutionalized elderly individuals, the annual incidence ranges from 25 to 44 per 1000, approximately four times higher than in those under 65.

Iterative Intraperitoneal Chemotherapy in Gastric Cancer Peritoneal Carcinomatosis.

Despite the incremental improvement of survival with systemic therapy in metastatic gastric cancer (GC), the outcomes of patients with peritoneal carcinomatosis (PC) remain poor. The limited effectiveness of systemic therapy is attributed to the blood-peritoneal barrier and anarchic intra-tumoral circulation, which reduce the penetration of systemic therapy. Approaches that incorporate intraperitoneal (IP) chemotherapy, in addition to systemic therapies, may be a viable alternate strategy.

FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone Resorption.

There are three FAM98 family proteins (FAM98A/B/C) in humans and mice. Their physiological functions remain largely unknown. We have previously reported that Fam98a interacts with Plekhm1 in murine osteoclasts and functions in lysosome trafficking/secretion and bone resorption in osteoclasts in vitro.

Validation of a Single Item Measure for Financial Toxicity Screening in Patients With Breast Cancer.

Purpose: Financial toxicity (FT) has been linked to higher symptom burden and poorer clinical outcomes for patients with cancer. Despite the availability of validated tools to measure FT, a simple screen remains an unmet need. We evaluated item 12 ("My illness has been a financial hardship to my family and me") of the COmprehensive Score for Financial Toxicity (COST) measure as a single-item FT screening measure.

The QUIC-SP: A Spanish language tool assessing unpredictability in early life is linked to physical and mental health.

Accumulating evidence indicates that unpredictable signals in early life represent a unique form of adverse childhood experiences (ACEs) associated with disrupted neurodevelopmental trajectories in children and adolescents. The Questionnaire of Unpredictability in Childhood (QUIC) was developed to assess early life unpredictability [1], encompassing social, emotional, and physical unpredictability in a child's environment, and has been validated in three independent cohorts. However, the importance of identifying ACEs in diverse populations, including non-English speaking groups, necessitates translation of the QUIC.

Synthesis and preclinical evaluation of tigilanol tiglate analogs as latency-reversing agents for the eradication of HIV.

Tigilanol tiglate (EBC-46) is a selective modulator of protein kinase C (PKC) isoforms that is Food and Drug Administration (FDA) approved for the treatment of mast cell tumors in canines with up to an 88% cure rate. Recently, it has been FDA approved for the treatment of soft tissue sarcomas in humans. The role of EBC-46 and, especially, its analogs in efforts to eradicate HIV, treat neurological and cardiovascular disorders, or enhance antigen density in antigen-targeted chimeric antigen receptor-T cell and chimeric antigen receptor-natural killer cell immunotherapies has not been reported.

A Spike-Based mRNA Vaccine Encapsulated in Phospholipid 1,2-Dioleoyl-sn-Glycero-3-PhosphoEthanolamine Containing Lipid Nanoparticles Induced Potent B- and T-Cell Responses Associated with Protection Against SARS-CoV-2 Infection and COVID-19-like Symptoms in Hamsters.

Background: Nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs) have emerged as a promising vaccine strategy, especially for COVID-19. While the LNPs protect mRNA from degradation and efficiently deliver the mRNA to antigen-presenting cells, the effect of lipid composition on the immunogenicity and protective efficacy of mRNA/LNP vaccines is not well characterized. Studies on using the mRNA/LNP platform for vaccines have largely focused on the nucleic acid cargo with less attention paid to the LNP vehicle.

Antigen Delivery Platforms for Next-Generation Coronavirus Vaccines.

The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is in its sixth year and is being maintained by the inability of current spike-alone-based COVID-19 vaccines to prevent transmission leading to the continuous emergence of variants and sub-variants of concern (VOCs). This underscores the critical need for next-generation broad-spectrum pan-Coronavirus vaccines (pan-CoV vaccine) to break this cycle and end the pandemic. The development of a pan-CoV vaccine offering protection against a wide array of VOCs requires two key elements: (1) identifying protective antigens that are highly conserved between passed, current, and future VOCs; and (2) developing a safe and efficient antigen delivery system for induction of broad-based and long-lasting B- and T-cell immunity.

Long term outcomes associated with the use of perioperative systemic chemotherapy on low grade appendiceal mucinous neoplasms with pseudomyxoma peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Introduction: Low grade appendiceal mucinous neoplasms (LAMN) are indolent tumors that lack invasive potential but may present as pseudomyxoma peritonei. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) significantly improves both overall and recurrence free survival. While systemic chemotherapy is generally considered ineffective for LAMN, little literature is available to support this notion.

Definition of a European pre-vasectomy scoring system to identify patients at risk of vasectomy regret.

Introduction: Vasectomy is a widely used, safe, effective method of permanent contraception and contributes to healthy sexuality.

Aims: We have conducted a 3-step observational clinical study to develop a vasectomy regret risk score and guide patients and clinicians when discussing a vasectomy.

Methods: A 3-step approach has been followed.

Combination adjuvant improves influenza virus immunity by downregulation of immune homeostasis genes in lymphocytes.

Adjuvants play a central role in enhancing the immunogenicity of otherwise poorly immunogenic vaccine antigens. Combining adjuvants has the potential to enhance vaccine immunogenicity compared with single adjuvants, although the cellular and molecular mechanisms of combination adjuvants are not well understood. Using the influenza virus hemagglutinin H5 antigen, we define the immunological landscape of combining CpG and MPLA (TLR-9 and TLR-4 agonists, respectively) with a squalene nanoemulsion (AddaVax) using immunologic and transcriptomic profiling.

Comparisons of neurodegenerative disease biomarkers across different biological fluids from patients with Huntington's disease.

Fluid biomarkers play important roles in many aspects of neurodegenerative diseases, such as Huntington's disease (HD). However, a main question relates to how well levels of biomarkers measured in CSF are correlated with those measured in peripheral fluids, such as blood or saliva. In this study, we quantified levels of four neurodegenerative disease-related proteins, neurofilament light (NfL), total tau (t-tau), glial fibrillary acidic protein (GFAP) and YKL-40 in matched CSF, plasma and saliva samples from Huntingtin (HTT) gene-positive individuals (n = 21) using electrochemiluminescence assays.

Ambient Air Pollution and COPD: The Multiethnic Cohort Study.

Rationale: Globally, in 2019, chronic obstructive pulmonary disease (COPD) was the third leading cause of death. While tobacco smoking is the predominant risk factor, the role of long-term air pollution exposure in increasing risk of COPD remains unclear. Moreover, there are few studies that have been conducted in racial and ethnic minoritized and socioeconomically diverse populations, while accounting for smoking history and other known risk factors.

Impact of Surgical Margin Status and Tumor Volume on Mortality After Robotic Radical Prostatectomy.

Background And Objective: Positive surgical margins (PSMs) following radical prostatectomy (RP) have been seen as inherently unfavorable. However, a large international multi-institutional study recently revealed that unifocal PSMs (UPSMs) had no impact on prostate cancer-specific mortality (PCSM), whereas multifocal PSMs (MPSMs) did. Our aim was to assess the relative impact of PSMs versus percentage tumor volume (PTV) on PCSM.

Novel photocrosslinking chemical probes utilized for high-resolution spatial transcriptomics.

The architecture of cells and the tissue they form within multicellular organisms are highly complex and dynamic. Cells optimize their function within tissue microenvironments by expressing specific subsets of RNAs. Advances in cell tagging methods enable spatial understanding of RNA expression when merged with transcriptomics.

Variations in Ciliary Beat Frequency Based on Chronic Rhinosinusitis Endotype and Phenotype.

Background: Chronic rhinosinusitis (CRS) is traditionally classified into CRS with or without nasal polyps and more recently into eosinophilic and non-eosinophilic endotypes. Limited research exists on the relationship between CRS subtype and mucociliary function. This study compares ciliary beat frequency (CBF) across CRS subtypes.

Evolution of long scalp hair in humans.

The ability to grow long scalp hair is a distinct human characteristic. It probably originally evolved to aid in cooling the sun-exposed head, although the genetic determinants of long hair are largely unknown. Despite ancestral variations in hair growth, long scalp hair is common to all extant human populations, which suggests its emergence before or concurrently with the emergence of anatomically modern humans (AMHs), approximately 300 000 years ago.

Exertional Compartment Syndrome Strategies for Evaluation and Management.

Objective: The exertional compartment syndrome (ECS) is often a delayed diagnosis. Compartment pressure measurements (CPM) confirm the diagnosis. Herein we present our algorithm for the evaluation and management (E&M) of ECS.

Enhanced suppression of by a three-phage cocktail: genomic insights and kinetic profiling.

is an understudied, gram-negative, aerobic bacterium that is widespread in the environment and increasingly a cause of opportunistic infections. Treating remains difficult, leading to an increase in disease severity and higher hospitalization rates in people with cystic fibrosis, cancer, and other immunocompromised health conditions. The lack of effective antibiotics has led to renewed interest in phage therapy; however, there remains a great need for well-characterized phages, especially against .

HEalth-Related Quality of Life-Intervention in Survivors of Breast and Other Cancers Experiencing Cancer-Related Fatigue and Associated Cognitive Symptoms Using TraditionAL Chinese Medicine: The 'HERBAL' Trial.

Introduction: As pharmacological strategies remain limited for relieving fatigue and associated cognitive symptoms, integrative modalities such as traditional Chinese medicine (TCM) could be explored as therapeutic strategies in cancer survivors. Here, we evaluate and report the efficacy and safety of a TCM concoction, modified Xiang Bei Yang Rong Tang (XBYRT), on quality of life (QOL), cancer-related fatigue (CRF), and cognitive symptoms, compared to placebo.

Methods: In a single-centered, randomized, double-blinded, placebo-controlled pilot trial conducted from 2019 to 2022, fatigued cancer survivors ≥21 years old were recruited to receive the XBYRT intervention or placebo (5% diluted) once daily for the duration of 8 weeks.

Same-Day Access for Head and Neck Cancer: Effect on Patient Outcome and Quality-Related Benchmarks.

Delays in cancer treatment are detrimental across nearly every disease site in oncology including head and neck cancer. This study aimed to evaluate the impact of same-day access for patients with newly diagnosed head and neck cancer referred for radiation therapy consultation. From March 2021 to March 2023, a total of 50 consecutive patients who completed curative treatment were matched to a control subject who did not use the same-day initiative based on age, gender, histology, performance status, primary tumor site, stage, p16 status, treatment, and smoking history.