Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein.

The most advanced monoclonal antibodies (mAbs) and vaccines against malaria target the central repeat region or closely related sequences within the circumsporozoite protein (PfCSP). Here, using an antigen-agnostic strategy to investigate human antibody responses to whole sporozoites, we identified a class of mAbs that target a cryptic PfCSP epitope that is only exposed after cleavage and subsequent pyroglutamylation (pGlu) of the newly formed N terminus. This pGlu-CSP epitope is not targeted by current anti-PfCSP mAbs and is not included in the licensed malaria vaccines.

An updated and expanded characterization of the biological sciences academic job market.

Introduction: In the biological sciences, many areas of uncertainty exist regarding the factors that contribute to success within the faculty job market. Earlier work from our group reported that beyond certain thresholds, academic and career metrics like the number of publications, fellowships or career transition awards, and years of experience did not separate applicants who received job offers from those who did not. Questions still exist regarding how academic and professional achievements influence job offers and if candidate demographics differentially influence outcomes.

Digital Health Tools for Miscarriage Support: A Survey of Canadian Women Facing Early Pregnancy Loss.

Objectives: Early pregnancy loss (EPL) affects 1 in 4 recognised pregnancies, yet often lacks patient-centred supportive care. This study assesses the feasibility and acceptance of a digital health tool to support those affected by EPL. The objectives are to (1) understand the experiences of those who have miscarried, (2) explore their methods of accessing health information, and (3) determine their preferences regarding digital tool content and design.

Notification, Viewing the Body, and Social and Cultural Considerations After Traumatic Death: A Systematic Literature Review.

We conducted a systematic review of the medical, nursing, forensic, and social science literature describing events and processes associated with what happens after a traumatic death in the socio-cultural context of largely Western and high-income societies. These include death notification, why survivors choose to view or not view the body, forensic practices affecting viewing the body, alternatives to viewing, and social and cultural practices following the death. We also describe how elements of these processes may act to increase or lessen some of the negative cognitive and emotional consequences for both survivors and providers.

A Systematic Review and Comparative Analysis of Reconstructive Rhytidectomy: Advantages, Disadvantages, and Patient Outcomes.

Reconstructive rhytidectomy, commonly known as facelift surgery, is a prominent cosmetic procedure aimed at rejuvenating facial appearance by addressing signs of aging. This paper critically evaluates the advantages and disadvantages of various surgical techniques involved in rhytidectomy, including the superficial musculoaponeurotic system (SMAS), deep plane facelift, and subperiosteal approaches. This systematic review of recent literature highlights key outcomes such as scar quality, postoperative pain management, and patient satisfaction.

Steric Activation in the Nazarov Cyclization of Fully Substituted Divinyl Ketones.

Fully substituted divinyl ketones (fsDVKs) have long been regarded as resistant to Nazarov cyclization (NC) unless they contain strategically positioned electronically activating substituents. Here, however, we show that fsDVKs bearing only electronically neutral alkyl or aryl groups actually undergo facile NC due to steric crowding in the pentadienyl cation intermediate, which raises its energy and reduces the barrier height to cyclization. Strongly ionizing and suitably bulky acid moieties further increase the energy of this intermediate cation, favoring cyclization.

Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates.

A mucosal route of vaccination could prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at the site of infection and limit transmission. We compared protection against heterologous XBB.1.

Variant-proof high affinity ACE2 antagonist limits SARS-CoV-2 replication in upper and lower airways.

SARS-CoV-2 has the capacity to evolve mutations that escape vaccine- and infection-acquired immunity and antiviral drugs. A variant-agnostic therapeutic agent that protects against severe disease without putting selective pressure on the virus would thus be a valuable biomedical tool that would maintain its efficacy despite the ongoing emergence of new variants. Here, we challenge male rhesus macaques with SARS-CoV-2 Delta-the most pathogenic variant in a highly susceptible animal model.

Methylene Blue in Septic Shock: A Systematic Review and Meta-Analysis.

Objectives: Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic review and meta-analysis to investigate the benefits and harms of MB administration in patients with septic shock.

Data Sources: We searched six databases (including PubMed, Embase, and Medline) from inception to January 10, 2024.

Sustainability of the Subspecialty of Anesthesiology Critical Care: An Expert Consensus and Review of the Literature.

While considerable literature exists with respect to clinical aspects of critical care anesthesiology (CCA) practice, few publications have focused on how anesthesiology-based critical care practices are organized and the challenges associated with the administration and management of anesthesiology critical care units. Currently, numerous challenges are affecting the sustainability of CCA practice, including decreased applications to fellowship positions and decreased reimbursement for critical care work. This review describes what is known about the subspecialty of CCA and leverages the experience of administrative leaders in adult critical care anesthesiologists in the United States to describe potential solutions.

Modelling the public health benefits of fibre fortification in the Chinese population through food reformulation.

Objectives: Various studies have highlighted how consuming adequate dietary fibre (DF) foods could confer multiple potential health benefits to humans, though data suggested that the average intake of the population is below the recommendations. The aim of this study, which involved probabilistic, mathematical and statistical modelling, was to understand, for the first time, how fibre fortification in a broad array of food categories could impact the diet and health status of Chinese consumers.

Design: A simulation-based approach was used to examine the potential impact of fibre fortification.

Reshaping the Tumor Microenvironment of KRASG12D Pancreatic Ductal Adenocarcinoma with Combined SOS1 and MEK Inhibition for Improved Immunotherapy Response.

Unlabelled: KRAS inhibitors have demonstrated exciting preclinical and clinical responses, although resistance occurs rapidly. Here, we investigate the effects of KRAS-targeting therapies on the tumor microenvironment using a library of KrasG12D, p53-mutant, murine pancreatic ductal adenocarcinoma-derived cell lines (KPCY) to leverage immune-oncology combination strategies for long-term tumor efficacy. Our findings show that SOS1 and MEK inhibitors (SOS1i+MEKi) suppressed tumor growth in syngeneic models and increased intratumoral CD8+ T cells without durable responses.

Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine.

A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole-sporozoite PfSPZ vaccine in African infants. Innate immune activation and myeloid signatures at prevaccination baseline correlated with protection from P. falciparum parasitemia in placebo controls.

A Review and Discussion of Full-Time Equivalency and Appropriate Compensation Models for an Adult Intensivist in the United States Across Various Base Specialties.

Objectives: Physicians with training in anesthesiology, emergency medicine, internal medicine, neurology, and surgery may gain board certification in critical care medicine upon completion of fellowship training. These clinicians often only spend a portion of their work effort in the ICU. Other work efforts that benefit an ICU infrastructure, but do not provide billing opportunities, include education, research, and administrative duties.

The Association of the Pulmonary Artery Pulsatility Index and Right Ventricular Function after Cardiac Surgery.

Background: The pulmonary artery pulsatility index (PAPi) has been shown to correlate with right ventricular (RV) failure in patients with cardiac disease. However, the association of PAPi with right ventricular function following cardiac surgery is not yet established.

Methods: PAPi and other hemodynamic variables were obtained postoperatively for 959 adult patients undergoing cardiac surgery.

Multi-Institutional Outcomes of Dorsal Onlay Buccal Mucosal Graft Urethroplasty in Patients With Postprostatectomy, Postradiation Anastomotic Stenosis.

Purpose: The treatment of urethral stenosis after a combination of prostatectomy and radiation therapy for prostate cancer is understudied. We evaluate the clinical and patient-related outcomes after dorsal onlay buccal mucosal graft urethroplasty (D-BMGU) in men who underwent prostatectomy and radiation therapy.

Materials And Methods: A multi-institutional, retrospective review of men with vesicourethral anastomotic stenosis or bulbomembranous urethral stricture disease after radical prostatectomy and radiation therapy from 8 institutions between 2013 to 2021 was performed.

Towards near-term quantum simulation of materials.

Determining the ground and excited state properties of materials is considered one of the most promising applications of quantum computers. On near-term hardware, the limiting constraint on such simulations is the requisite circuit depths and qubit numbers, which currently lie well beyond near-term capabilities. Here we develop a quantum algorithm which reduces the estimated cost of material simulations.

Durable immunity to SARS-CoV-2 in both lower and upper airways achieved with a gorilla adenovirus (GRAd) S-2P vaccine in non-human primates.

SARS-CoV-2 continues to pose a global threat, and current vaccines, while effective against severe illness, fall short in preventing transmission. To address this challenge, there's a need for vaccines that induce mucosal immunity and can rapidly control the virus. In this study, we demonstrate that a single immunization with a novel gorilla adenovirus-based vaccine (GRAd) carrying the pre-fusion stabilized Spike protein (S-2P) in non-human primates provided protective immunity for over one year against the BA.

Mucosal Adenoviral-vectored Vaccine Boosting Durably Prevents XBB.1.16 Infection in Nonhuman Primates.

Waning immunity and continued virus evolution have limited the durability of protection from symptomatic infection mediated by intramuscularly (IM)-delivered mRNA vaccines against COVID-19 although protection from severe disease remains high. Mucosal vaccination has been proposed as a strategy to increase protection at the site of SARS-CoV-2 infection by enhancing airway immunity, potentially reducing rates of infection and transmission. Here, we compared protection against XBB.