A Phage-Based Approach to Identify Antivirulence Inhibitors of Bacterial Type IV Pili.

The increasing threat of antibiotic resistance underscores the urgent need for innovative strategies to combat infectious diseases, including the development of antivirulants. Microbial pathogens rely on their virulence factors to initiate and sustain infections. Antivirulants are small molecules designed to target virulence factors, thereby attenuating the virulence of infectious microbes.

Targeted inhibition of Aurora kinase A promotes immune checkpoint inhibition efficacy in human papillomavirus-driven cancers.

Background: Human papillomavirus (HPV)-driven cancers include head and neck squamous cell carcinoma and cervical cancer and represent approximately 5% of all cancer cases worldwide. Standard-of-care chemotherapy, radiotherapy, and immune checkpoint inhibitors (ICIs) are associated with adverse effects and limited responses in patients with HPV-driven cancers. The integration of targeted therapies with ICIs may improve outcomes.

Phase 1/2 Study of the Aurora Kinase A Inhibitor Alisertib and Pembrolizumab in Refractory, Rb-Deficient Head and Neck Squamous Cell Carcinomas.

Purpose: Effective therapy for recurrent head and neck squamous cell carcinoma (HNSCC) that is refractory to chemotherapy and immunotherapy is a considerable need. Aurora kinase A inhibition leads to apoptosis and immunogenic cell death in preclinical models of human papilloma virus (HPV)-driven cancers.

Experimental Design: Alisertib was administered orally twice daily on days 1-7 and pembrolizumab on day 1 of a 21-day cycle to adults with advanced solid tumors (phase 1) or with immunotherapy- and platinum-resistant, HPV-positive HNSCC (phase 2).

Phase II Study of Palbociclib in Patients with Tumors with CDK4 or CDK6 Amplification: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1C.

Purpose: Amplification of cyclin-dependent kinase 4 (CDK4) and CDK6 is a feature of a variety of malignancies, and preclinical evidence suggests that inhibition of CDK4/6 is a plausible treatment strategy in these tumors. Subprotocol Z1C of the NCI-Molecular Analysis for Therapy Choice trial was designed to evaluate the CDK4/6 inhibitor palbociclib in CDK4- or CDK6-amplified tumors.

Patients And Methods: Patients had a solid malignancy or lymphoma with progression on at least one systemic therapy for advanced disease or with no standard-of-care therapy available.

Long COVID and Health Inequalities: What's Next for Research and Policy Advocacy?

Introduction: Organised by the 'Qualitative Long Covid Network', a workshop for qualitative Long COVID (LC) researchers, LC charity representatives and people with LC took place in June 2023, where research on the intersectional inequalities affecting LC prevalence, recognition and care was shared and discussed.

Methods: Five key themes were drawn up from presentations, discussions and reflections during the workshop, which are presented in this study.

Results: The following five themes are discussed: the unfairness of LC, difficulties in accessing care, mistrust of the healthcare system, a lack of understanding of LC and experiences of stigma and discrimination.

Environmental Sustainability Initiatives in the Operating Room: A Scoping Review.

The global healthcare industry has a substantial environmental footprint and therefore has a responsibility to decrease its impact. Changes to increase sustainability will only occur if healthcare providers (HCPs) and decision-makers understand and incorporate environmentally conscious practices in the operating room (OR). This scoping review aimed to assess hospital initiatives undertaken to support environmental sustainability in the OR, with a focus on HCP and hospital decision-maker beliefs and perceptions related to sustainability.

Surface hydrophilicity promotes bacterial twitching motility.

Unlabelled: Twitching motility is a form of bacterial surface translocation powered by the type IV pilus (T4P). It is frequently analyzed by interstitial colony expansion between agar and the polystyrene surfaces of petri dishes. In such assays, the twitching motility of was observed with MacConkey but not Luria-Bertani (LB) agar media.

Health screening clinic to reduce absenteeism and presenteeism among NHS Staff: eTHOS a pilot RCT.

Background: Staff sickness absenteeism and presenteeism (attending work while unwell) incur high costs to the NHS, are associated with adverse patient outcomes and have been exacerbated by the COVID-19 pandemic. The main causes are mental and musculoskeletal ill health with cardiovascular risk factors common.

Objectives: To undertake a feasibility study to inform the design of a definitive randomised controlled trial of the effectiveness and cost effectiveness of a health screening clinic in reducing absenteeism and presenteeism amongst the National Health Service staff.

KRAS-Driven Tumorigenesis and KRAS-Driven Therapy in Pancreatic Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is associated with significant morbidity and mortality and is projected to be the second leading cause of cancer-related deaths by 2030. Mutations in KRAS are found in the vast majority of PDAC cases and plays an important role in the development of the disease. KRAS drives tumor cell proliferation and survival through activating the MAPK pathway to drive cell cycle progression and to lead to MYC-driven cellular programs.

AAPM task group report 288: Recommendations for guiding radiotherapy event narratives.

Incident reporting and learning systems provide an opportunity to identify systemic vulnerabilities that contribute to incidents and potentially degrade quality. The narrative of an incident is intended to provide a clear, easy to understand description of an incident. Unclear, incomplete or poorly organized narratives compromise the ability to learn from them.

Circulating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma.

While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA levels and survival have not been examined. Here we investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall and progression-free survival (OS/PFS) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) for patients receiving chemoimmunotherapy ("PRINCE", NCT03214250), and an independent cohort receiving standard of care (SOC) chemotherapy. For PRINCE, higher baseline plasma levels are associated with worse OS for ctKRAS G12D (log-rank p = 0.

Development of a quality of life measure for left ventricular assist device recipients using a mixed methods approach.

Background: Left ventricular assist device (LVAD) recipients report symptom improvement but find adjusting to life with the LVAD challenging. These challenges are unique, and existing patient-reported outcome measures (PROMs) do not reflect their experiences. This study aimed to develop a culturally relevant quality of life PROM for use with LVAD recipients in future research, design evolutions and clinical practice.

Combining antivascular endothelial growth factor and anti-epidermal growth factor receptor antibodies: randomized phase II study of irinotecan and cetuximab with/without ramucirumab in second-line colorectal cancer (ECOG-ACRIN E7208).

Background: Early studies showed promise of combined anti-epidermal growth factor receptor (EGFR) plus anti-vascular endothelial growth factor (VEGF) antibodies for advanced colorectal cancer (CRC), yet this was later rejected as toxic and ineffective in studies not selected for RAS status. We studied advanced KRAS wild-type CRC, as second-line treatment, using irinotecan-cetuximab with or without the anti-VEGF receptor antibody ramucirumab.

Methods: Patients with 1 prior regimen including fluoropyrimidine, oxaliplatin, and bevacizumab, with KRAS wild-type tumors were stratified by Eastern Cooperative Oncology Group Performance Score, time since last chemotherapy, and progression on oxaliplatin to irinotecan-cetuximab (IC) (180 mg/m2 and 500 mg/m2 every 2 weeks) vs modified ICR (irinotecan-cetuximab with ramucirumab 150 mg/m2 and 400 mg/m2 plus 6 mg/kg, respectively).

From pregnancy to the postpartum: Unraveling the complexities of symptom profiles among trauma-exposed women.

Background: Many women experience new onset or worsening of existing posttraumatic stress disorder (PTSD) symptoms during pregnancy and the early postpartum period. However, perinatal PTSD symptom profiles and their predictors are not well understood.

Methods: Participants (N = 614 community adults) completed self-report measures across three methodologically similar longitudinal studies.

The role of blood testing in prevention, diagnosis, and management of chronic diseases: A review.

Blood tests are vital to prevention, diagnosis, and management of chronic diseases. Despite this, it can be challenging to construct a comprehensive view of the clinical importance of blood testing because relevant literature is typically fragmented across different disease areas and patient populations. This lack of collated evidence can also make it difficult for primary care providers to adhere to best practices for blood testing across different diseases and guidelines.

The NFκB Dif is required for behavioral and molecular correlates of sleep homeostasis in Drosophila.

The nuclear factor binding the κ light chain in B-cells (NFκB) is involved in a wide range of cellular processes including development, growth, innate immunity, and sleep. However, genetic studies of the role of specific NFκB transcription factors in sleep have been limited. Drosophila fruit flies carry three genes encoding NFκB transcription factors, Dorsal, Dorsal Immunity Factor (Dif), and Relish.

Exploring the needs and experiences of contact tracing staff during the COVID-19 pandemic in Ireland.

Background: Contact tracing is a key component in controlling the spread of COVID-19, however little research has focused on learning from the experiences of contact tracing staff. Harnessing learning from those in this role can provide valuable insights into the process of contact tracing and how best to support staff in this crucial role.

Methods: Thematic analysis was used to analyse 47 semi-structured interviews conducted with contact tracing staff via telephone or Zoom at three time points in 2021: March, May and September-October.

The effect of four different object properties on latency to approach in Goffin's cockatoos (Cacatua goffiniana).

Neophobia and neophilia can be lifesaving as they can facilitate foraging while avoiding predation or intoxication. We investigated the extent to which Goffin's cockatoos () exhibit ecollogically relevant and quantifiable neophobic responses toward specific object properties. Twelve cockatoos were presented with 12 novel objects grouped into four distinct categories with unique features: size, color, reflective capacity, and shape.

Immunity from NK Cell Subsets Is Important for Vaccine-Mediated Protection in HPV+ Cancers.

High-risk human papillomaviruses (HPVs) are associated with genital and oral cancers, and the incidence of HPV+ head and neck squamous cell cancers is fast increasing in the USA and worldwide. Survival rates for patients with locally advanced disease are poor after standard-of-care chemoradiation treatment. Identifying the antitumor host immune mediators important for treatment response and designing strategies to promote them are essential.

Relationships between physical fitness characteristics, technical skill attributes, and sports injury in female Australian football players.

Objectives: To explore the relationships between physical fitness and i) technical skills and ii) time-loss from Australian football injury in female players across the talent and participation pathways.

Methods: This study uses a subset of data from two cross-sectional and one prospective cohort studies. A total of 223 female Australian football players across five competition levels (elite/non-elite senior, high-level junior, and non-elite junior (14-17 years)/(10-13 years)) were included in this study.