Electroporation-mediated novel albumin-fused Flt3L DNA delivery promotes cDC1-associated anticancer immunity.

Dendritic cells (DCs) constitute a distinct type of immune cell found within tumors, serving a central role in mediating tumor antigen-specific immunity against cancer cells. Frequently, DC functions are dysregulated by the immunosuppressive signals present within the tumor microenvironment (TME). Consequently, DC manipulation holds great potential to enhance the cytotoxic T cell response against cancer diseases.

STAT1-Deficient HPV E6/E7-Associated Cancers Maintain Host Immunocompetency against Therapeutic Intervention.

Human papillomavirus (HPV) remains a global health concern because it contributes to the initiation of various HPV-associated cancers such as anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancer. In HPV-associated cancers, oncogenesis begins with an HPV infection, which is linked to the activation of the Janus protein tyrosine kinase (JAK)/STAT signaling pathway. Various STAT signaling pathways, such as STAT3 activation, have been well documented for their tumorigenic role, yet the role of STAT1 in tumor formation remains unclear.

Arginine-linked HPV-associated E7 displaying bacteria-derived outer membrane vesicles as a potent antigen-specific cancer vaccine.

Background: Bacteria-based cancer therapy have demonstrated innovative strategies to combat tumors. Recent studies have focused on gram-negative bacterial outer membrane vesicles (OMVs) as a novel cancer immunotherapy strategy due to its intrinsic properties as a versatile carrier.

Method: Here, we developed an Human Papillomavirus (HPV)-associated E7 antigen displaying Salmonella-derived OMV vaccine, utilizing a Poly(L-arginine) cell penetrating peptide (CPP) to enhance HPV16 E7 (aa49-67) H-2 Db and OMV affinity, termed SOMV-9RE7.

Industry Perceptions and Experiences with the Access Consortium New Active Substance Work-Sharing Initiative (NASWSI): Survey Results and Recommendations.

The Access Consortium New Active Substance Work-Sharing Initiative, or "Access" for simplicity, allows regulatory authorities (RAs) of the Access Consortium countries to jointly review applications for the registration of new active substances or for new indications. Using a survey developed by the pharmaceutical industry trade associations of the five Access Consortium countries-Australia, Canada, Singapore, Switzerland, and the United Kingdom (UK)-this study gathered insights into the perceptions and experiences of the Access pathway held by affiliates of pharmaceutical companies. Understanding industry perceptions of Access is important for the success of the initiative, as participation is voluntary.

A Learning Assessment to Increase Diversity in Academic Health Sciences.

Importance: Strategies and innovations to advance racial and ethnic equity in recruitment, promotion, and retention at academic health science institutions are needed.

Objective: This learning assessment aims to isolate evidence-based strategies to advance racial equity in the academic health sciences, which have implications for policy and institution-level interventions.

Evidence Review: This learning assessment used a mixed-methods approach, including a quantitative survey, qualitative in-depth interviews, and a scoping literature review.

immunotherapy engineered with highly efficient tumor antigen coating establishes antigen-specific CD8+ T cell immunity and increases in antitumor efficacy with type I interferon combination therapy.

Bacteria-based cancer therapy employs various strategies to combat tumors, one of which is delivering tumor-associated antigen (TAA) to generate specific immunity. Here, we utilized a poly-arginine extended HPV E7 antigen (9RE7) for attachment on Salmonella SL7207 outer membrane to synthesize the bacterial vaccine Salmonella-9RE7 (Sal-9RE7), which yielded a significant improvement in the amount of antigen presentation compared to the previous lysine-extended antigen coating strategy. In TC-1 tumor mouse models, Sal-9RE7 monotherapy decreased tumor growth by inducing E7 antigen-specific immunity.

Referrals to Community and State Agencies to Address Social Determinants of Health for Improving Mental Health, Functioning, and Quality of Care Outcomes for Diverse Adults.

To examine whether referral for social determinants of health (SDH) needs decreases psychological distress and posttraumatic stress disorder (PTSD) symptoms and improves level of functioning and quality of care among diverse adults. Data are from control participants (n = 503 adults) in a randomized controlled trial testing a mental health intervention in North Carolina and Massachusetts. We fitted multilevel mixed-effects models to repeated assessments (baseline, 3, 6, and 12 months) collected between September 2019 and January 2023.

Immune responses, therapeutic anti-tumor effects, and tolerability upon therapeutic HPV16/18 E6/E7 DNA vaccination via needle-free biojector.

Respectively, HPV16 and HPV18 cause 50% and 20% of cervical cancer cases globally. Viral proteins E6 and E7 are obligate drivers of oncogenic transformation. We recently developed a candidate therapeutic DNA vaccine, pBI-11, that targets HPV16 and HPV18 E6 and E7.

Applying a Smartwatch to Predict Work-related Fatigue for Emergency Healthcare Professionals: Machine Learning Method.

Introduction: Healthcare professionals frequently experience work-related fatigue, which may jeopardize their health and put patient safety at risk. In this study, we applied a machine learning (ML) approach based on data collected from a smartwatch to construct prediction models of work-related fatigue for emergency clinicians.

Methods: We conducted this prospective study at the emergency department (ED) of a tertiary teaching hospital from March 10-June 20, 2021, where we recruited physicians, nurses, and nurse practitioners.

Recent Advances on Social Determinants of Mental Health: Looking Fast Forward.

The fields of psychiatry and mental health are increasingly recognizing the importance of social determinants of health (SDOH) and their impact on mental health outcomes. In this overview, the authors discuss the recent research, from the past 5 years, on advances made in SDOH work. SDOH frameworks and theories have expanded to include more social conditions, from traumas associated with immigration to psychosocial and community strengths, that impact mental health and well-being.

Intersectional approaches are essential to identify the multiple sources of oppression.

Intersectional and multilevel approaches are required to tackle mental health disparities for marginalized populations. Intersectionality offers a guiding framework to study how social structures and systems work at multiple socioecological levels to influence the health and well-being of minoritized communities. This special section showcases research using intersectional approaches elucidating mental health and psychopathology outcomes among diverse populations.

Biogeographic and disease-specific alterations in epidermal lipid composition and single-cell analysis of acral keratinocytes.

The epidermis is the outermost layer of skin. Here, we used targeted lipid profiling to characterize the biogeographic alterations of human epidermal lipids across 12 anatomically distinct body sites, and we used single-cell RNA-Seq to compare keratinocyte gene expression at acral and nonacral sites. We demonstrate that acral skin has low expression of EOS acyl-ceramides and the genes involved in their synthesis, as well as low expression of genes involved in filaggrin and keratin citrullination (PADI1 and PADI3) and corneodesmosome degradation, changes that are consistent with increased corneocyte retention.

Brain-wide neural dynamics of poststroke recovery induced by optogenetic stimulation.

Poststroke optogenetic stimulations can promote functional recovery. However, the circuit mechanisms underlying recovery remain unclear. Elucidating key neural circuits involved in recovery will be invaluable for translating neuromodulation strategies after stroke.

Why are the batteries in the microwave?: Use of semantic information under uncertainty in a search task.

A major problem in human cognition is to understand how newly acquired information and long-standing beliefs about the environment combine to make decisions and plan behaviors. Over-dependence on long-standing beliefs may be a significant source of suboptimal decision-making in unusual circumstances. While the contribution of long-standing beliefs about the environment to search in real-world scenes is well-studied, less is known about how new evidence informs search decisions, and it is unclear whether the two sources of information are used together optimally to guide search.

A review and roadmap of the skin, lung and gut microbiota in systemic sclerosis.

As our understanding of the genetic underpinnings of SSc increases, questions regarding the environmental trigger(s) that induce and propagate SSc in the genetically predisposed individual emerge. The interplay between the environment, the immune system, and the microbial species that inhabit the patient's skin and gastrointestinal tract is a pathobiological frontier that is largely unexplored in SSc. The purpose of this review is to provide an overview of the methodologies, experimental study results and future roadmap for elucidating the relationship between the SSc host and his/her microbiome.

Contrasting lexical biases in bilingual English-Mandarin speech: Verb-biased mothers, but noun-biased toddlers.

Is noun dominance in early lexical acquisition a widespread or a language-specific phenomenon? Thirty Singaporean bilingual English-Mandarin learning toddlers and their mothers were observed in a mother-child play interaction. For both English and Mandarin, toddlers' speech and reported vocabulary contained more nouns than verbs across book reading and toy playing. In contrast, their mothers' speech contained more verbs than nouns in both English and Mandarin but differed depending on the context of the interaction.

Unique Subtype of Microglia in Degenerative Thalamus After Cortical Stroke.

Background And Purpose: Stroke disrupts neuronal functions in both local and remotely connected regions, leading to network-wide deficits that can hinder recovery. The thalamus is particularly affected, with progressive development of neurodegeneration accompanied by inflammatory responses. However, the complexity of the involved inflammatory responses is poorly understood.

Computer vision applied to dual-energy computed tomography images for precise calcinosis cutis quantification in patients with systemic sclerosis.

Background: Although treatments have been proposed for calcinosis cutis (CC) in patients with systemic sclerosis (SSc), a standardized and validated method for CC burden quantification is necessary to enable valid clinical trials. We tested the hypothesis that computer vision applied to dual-energy computed tomography (DECT) finger images is a useful approach for precise and accurate CC quantification in SSc patients.

Methods: De-identified 2-dimensional (2D) DECT images from SSc patients with clinically evident lesser finger CC lesions were obtained.

The development and testing of a nurse-led smartphone-based self-management programme for diabetes patients with poor glycaemic control.

Aims: To describe a systematic process for the development of a nurse-led smartphone-based self-management programme for type 2 diabetes patients with poor glycaemic control in Singapore.

Methods: A three-step process involving the application of a theoretical framework, evidence from literature, content validity, and pilot tests were conducted for the content and technical development of the programme. Content experts and lay patients evaluated the appropriateness, relevance, and comprehensibility of the newly developed Care4Diabetes application.