Identification and characterization of vasoactive intestinal peptide receptor antagonists with high-affinity and potent anti-leukemia activity.

Vasoactive intestinal peptide (VIP) is a neuropeptide involved in tumor growth and immune modulating functions. Previous research indicated that a VIP antagonist (VIPhyb) enhances T-cell activation and induces T-cell-dependent anti-leukemic activity in mice. We created a combinatorial library of VIPhyb C-terminal sequence variations to develop a more potent VIP-receptor (VIP-R) antagonist, hypothesizing that specific amino acid substitutions would improve receptor binding and plasma stability.

Meeting report: Considerations for trial design and endpoints in licensing therapeutic HPV16/18 vaccines to prevent cervical cancer.

Cervical cancer is a major cause of morbidity and mortality globally with a disproportionate impact on women in low- and middle-income countries. In 2021, the World Health Organization (WHO) called for increased vaccination, screening, and treatment to eliminate cervical cancer. However, even with widespread rollout of human papillomavirus (HPV) prophylactic vaccines, millions of women who previously acquired HPV infections will remain at risk for progression to cancer for decades to come.

Inferring the natural history of HPV from global cancer registries: insights from a multi-country calibration.

Human papillomavirus (HPV) is the cause of almost all cases of cervical cancer, a disease that kills some 340,000 women per year. The timeline from initial infection with HPV to the onset of invasive cervical cancer spans decades, and observational studies of this process are limited to settings in which treatment of precancerous lesions was withheld or inadequate. Such studies have been critical for understanding the natural history of HPV.

HPVsim: An agent-based model of HPV transmission and cervical disease.

In 2020, the WHO launched its first global strategy to accelerate the elimination of cervical cancer, outlining an ambitious set of targets for countries to achieve over the next decade. At the same time, new tools, technologies, and strategies are in the pipeline that may improve screening performance, expand the reach of prophylactic vaccines, and prevent the acquisition, persistence and progression of oncogenic HPV. Detailed mechanistic modelling can help identify the combinations of current and future strategies to combat cervical cancer.

Survivorship wellness: a multidisciplinary group program for cancer survivors.

Purpose: National mandates require cancer centers provide comprehensive survivorship care. We created an 8-session, group intervention, the Survivorship Wellness Group Program (SWGP), that covered 8 topics: nutrition, physical activity, stress, sleep/fatigue, sexuality/body image, emotional wellbeing/fear of cancer recurrence, spirituality/meaning, and health promotion/goal setting. This study examined the acceptability and preliminary outcomes of SWGP.

The changing health impact of vaccines in the COVID-19 pandemic: A modeling study.

Much of the world's population had already been infected with COVID-19 by the time the Omicron variant emerged at the end of 2021, but the scale of the Omicron wave was larger than any that had come before or has happened since, and it left a global imprinting of immunity that changed the COVID-19 landscape. In this study, we simulate a South African population and demonstrate how population-level vaccine effectiveness and efficiency changed over the course of the first 2 years of the pandemic. We then introduce three hypothetical variants and evaluate the impact of vaccines with different properties.

Impact of SARS-CoV-2 Gamma lineage introduction and COVID-19 vaccination on the epidemiological landscape of a Brazilian city.

Background: The emergence of the Brazilian variant of concern, Gamma lineage (P.1), impacted the epidemiological profile of COVID-19 cases due to its higher transmissibility rate and immune evasion ability.

Methods: We sequenced 305 SARS-CoV-2 whole-genomes and performed phylogenetic analyses to identify introduction events and the circulating lineages.

A case study and proposal for publishing directed acyclic graphs: The effectiveness of the quadrivalent human papillomavirus vaccine in perinatally HIV Infected girls.

Background: Developing a causal graph is an important step in etiologic research planning and can be used to highlight data flaws and irreparable bias and confounding. As a case study, we consider recent findings that suggest human papillomavirus (HPV) vaccine is less effective against HPV-associated disease among girls living with HIV compared to girls without HIV.

Objectives: To understand the relationship between HIV status and HPV vaccine effectiveness, it is important to outline the key assumptions of the causal mechanisms before designing a study to investigate the effect of the HPV vaccine in girls living with HIV infection.

Covasim: An agent-based model of COVID-19 dynamics and interventions.

The COVID-19 pandemic has created an urgent need for models that can project epidemic trends, explore intervention scenarios, and estimate resource needs. Here we describe the methodology of Covasim (COVID-19 Agent-based Simulator), an open-source model developed to help address these questions. Covasim includes country-specific demographic information on age structure and population size; realistic transmission networks in different social layers, including households, schools, workplaces, long-term care facilities, and communities; age-specific disease outcomes; and intrahost viral dynamics, including viral-load-based transmissibility.

Controlling COVID-19 via test-trace-quarantine.

Initial COVID-19 containment in the United States focused on limiting mobility, including school and workplace closures. However, these interventions have had enormous societal and economic costs. Here, we demonstrate the feasibility of an alternative control strategy, test-trace-quarantine: routine testing of primarily symptomatic individuals, tracing and testing their known contacts, and placing their contacts in quarantine.

Mathematical modelling of respiratory syncytial virus (RSV) in low- and middle-income countries: A systematic review.

Background: Due to high burden of respiratory syncytial virus (RSV) in low- and middle-income countries (LMIC), international funding organizations have prioritized the development of RSV vaccines. Mathematical models of RSV will play an important role in assessing the relative value of these interventions. Our objectives were to provide an overview of the existing RSV modelling literature in LMIC and summarize available results on population-level effectiveness and cost-effectiveness.

Impact and Cost-Effectiveness of Human Papillomavirus Vaccination Campaigns.

Background: Data to inform evidence-based policy of human papillomavirus (HPV) vaccine delivery strategies in low- and middle-income countries are limited. We examined the cost-effectiveness of campaign compared with routine delivery strategies of adolescent female HPV vaccination in Uganda.

Methods: We used a multiple modeling approach that captured HPV transmission, cervical carcinogenesis, and population demographics to project health and economic outcomes associated with HPV vaccination.

Associations of the Mediterranean diet with cognitive and neuroimaging phenotypes of dementia in healthy older adults.

Background: Accumulating evidence suggests that higher Mediterranean diet (MedDiet) adherence is associated with higher global cognitive performance and brain structural integrity as well as decreased risk of Alzheimer disease (AD) and vascular dementia (VaD).

Objectives: We directly examined cross-sectional associations between the MedDiet and cognitive and neuroimaging phenotypes associated with AD and VaD (separately) in a cohort of nondemented, nondepressed older adults.

Methods: Community-dwelling older adults (n = 82; aged ∼68.

Divergent Influences of Cardiovascular Disease Risk Factor Domains on Cognition and Gray and White Matter Morphology.

Objective: Hypertension, diabetes, dyslipidemia, and obesity are associated with preclinical alterations in cognition and brain structure; however, this often comes from studies of comprehensive risk scores or single isolated factors. We examined associations of empirically derived cardiovascular disease risk factor domains with cognition and brain structure.

Methods: A total of 124 adults (age, 59.

Studies of Physician-Patient Communication with Older Patients: How Often is Hearing Loss Considered? A Systematic Literature Review.

Hearing loss is remarkably prevalent in the geriatric population: one-quarter of adults aged 60-69 and 80% of adults aged 80 years and older have bilateral disabling loss. Only about one in five adults with hearing loss wears a hearing aid, leaving many vulnerable to poor communication with healthcare providers. We quantified the extent to which hearing loss is mentioned in studies of physician-patient communication with older patients, and the degree to which hearing loss is incorporated into analyses and findings.

Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis.

Physical activity (PA) is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models.

Cognitive and connectome properties detectable through individual differences in graphomotor organization.

We investigated whether graphomotor organization during a digitized Clock Drawing Test (dCDT) would be associated with cognitive and/or brain structural differences detected with a tractography-derived structural connectome of the brain. 72 non-demented/non-depressed adults were categorized based on whether or not they used 'anchor' digits (i.e.

A Thoracotomy Approach for the Surgical Repair of a Left Ventricular Free Wall Rupture.

In the current era of rapid culprit vessel revascularization in acute myocardial infarction, ventricular free wall rupture is becoming increasingly uncommon. In rare cases adherent pericardium may contain this rupture, creating a temporary stable pseudoaneurysm. With the aid of intraoperative pictures, we describe herein a left thoracotomy approach for the surgical correction of a left ventricular pseudoaneurysm secondary to free wall rupture.

What Metabolic Syndrome Contributes to Brain Outcomes in African American & Caucasian Cohorts.

Metabolic syndrome (MetS), i.e., meeting criteria for any three of the following: hyperglycemia, hypertension, hypertriglyceridemia, low high-density lipoprotein and/or abdominal obesity, is associated with negative health outcomes.

Reconciling the science and policy divide: The reality of scaling up antiretroviral therapy in South Africa.

With the world's largest national treatment programme and over 340 000 incident cases annually, the response to HIV in South Africa is hotly contested and there is sometimes a dissonance between activism, science and policy. Too often, policy, whilst well intentioned, is informed only by epidemiological data. The state of the healthcare system and sociocultural factors drive and shape the epidemic and its response.