Refractory immune TTP following Pfizer-BioNTech COVID-19 vaccine successfully salvaged with caplacizumab.

Immune thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy caused by antibodies against ADAMTS13. We report a young, healthy female who developed hematuria, vomiting, and hematemesis 3 weeks after her first dose of Pfizer Bio-NTech COVID-19 vaccine. Investigations confirmed iTTP with undetectable ADAMTS13 activity and a positive antibody assay.

A confounding bronchopulmonary situs abnormality after bilateral lung transplantation.

A 36-year-old female with a past medical history of primary ciliary dyskinesia and bilateral lung transplantation was noted to have a rare and confounding postsurgical anatomy acquired as a result of transplantation. Bronchoscopy and computed tomography showed isomeric main bronchi with a tri-lobed right lung, a bi-lobed left lung and dextrocardia. This rare phenomenon can be observed in lung transplant recipients with situs ambiguous morphology of their native lungs, who receive donor lungs with normal situs solitus morphology.

The Sit-to-Stand Transition as a Biomarker for Impairment: Comparison of Instrumented 30-Second Chair Stand Test and Daily Life Transitions in Multiple Sclerosis.

Falls and mobility deficits are common in people with multiple sclerosis (PwMS) across all levels of clinical disability. However, functional mobility observed in supervised settings may not reflect daily life which may impact assessments of fall risk and impairment in the clinic. To investigate this further, we compared the utility of sensor-based performance metrics from sit-stand transitions during daily life and a structured task to inform fall risk and impairment in PwMS.

Cytotoxic and Inflammatory Effects of Electronic and Traditional Cigarettes on Oral Gingival Cells Using a Novel Automated Smoking Instrument: An In Vitro Study.

Information about the potential oral health effects of vaping from electronic cigarettes (e-cigs) is still sparse and inconsistent. The purpose of this study was to compare the safety and cytotoxicity of e-cig liquid aerosols versus traditional cigarette (t-cig) smoke on human epithelial oral cells. T-cig smoke and e-cig aerosols were generated by a newly developed automated smoking instrument in order to simulate realistic user puffing behaviors.

Bacterial Membranes Are More Perturbed by the Asymmetric Versus Symmetric Loading of Amphiphilic Molecules.

Characterizing the biophysical properties of bacterial membranes is critical for understanding the protective nature of the microbial envelope, interaction of biological membranes with exogenous materials, and designing new antibacterial agents. Presented here are molecular dynamics simulations for two cationic quaternary ammonium compounds, and the anionic and nonionic form of a fatty acid molecule interacting with a bacterial inner membrane. The effect of the tested materials on the properties of the model membranes are evaluated with respect to various structural properties such as the lateral pressure profile, lipid tail order parameter, and the bilayer's electrostatic potential.

Behavioral Ethics Ecologies of Human-Artificial Intelligence Systems.

Historically, evolution of behaviors often took place in environments that changed little over millennia. By contrast, today, rapid changes to behaviors and environments come from the introduction of artificial intelligence (AI) and the infrastructures that facilitate its application. Behavioral ethics is concerned with how interactions between individuals and their environments can lead people to questionable decisions and dubious actions.

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States.

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.

Findings from precision oncology in the clinic: rare, novel variants are a significant contributor to scaling molecular diagnostics.

Background: Next generation sequencing for oncology patient management is now routine in clinical pathology laboratories. Although wet lab, sequencing and pipeline tasks are largely automated, the analysis of variants for clinical reporting remains largely a manual task. The increasing volume of sequencing data and the limited availability of genetic experts to analyse and report on variants in the data is a key scalability limit for molecular diagnostics.

Fire as a driver of fungal diversity - A synthesis of current knowledge.

Fires occur in most terrestrial ecosystems where they drive changes in the traits, composition, and diversity of fungal communities. Fires range from rare, stand-replacing wildfires to frequent, prescribed fires used to mimic natural fire regimes. Fire regime factors, including burn severity, fire intensity, and timing, vary widely and likely determine how fungi respond to fires.

Palliative care for older people with dementia-we need a paradigm shift in our approach.

Older people with dementia have multiple palliative care needs, with pain, agitation, dyspnoea, aspiration and pressure ulcers being common and persistent in advanced dementia. Anticipating the person's possible symptoms requires knowledge of the whole person, including the type of dementia, which is problematic when the dementia type is often not documented. A palliative care approach to dementia should look at symptoms across the four pillars of palliative care, but in reality, we tend to over-focus on physical and psychological symptoms, while spiritual and emotional needs can be overlooked, especially around the time of diagnosis, where such needs may be significant.

Transcriptomic Biomarker Signatures for Discrimination of Oral Cancer Surgical Margins.

Relapse after surgery for oral squamous cell carcinoma (OSCC) contributes significantly to morbidity, mortality and poor outcomes. The current histopathological diagnostic techniques are insufficiently sensitive for the detection of oral cancer and minimal residual disease in surgical margins. We used whole-transcriptome gene expression and small noncoding RNA profiles from tumour, close margin and distant margin biopsies from 18 patients undergoing surgical resection for OSCC.

Protonation-Dependent Sequencing of 5-Formylcytidine in RNA.

Chemical modification of cytidine in noncoding RNAs plays a key role in regulating translation and disease. However, the distribution and dynamics of many of these modifications remain unknown due to a lack of sensitive site-specific sequencing technologies. Here, we report a protonation-dependent sequencing reaction for the detection of 5-formylcytidine (5fC) and 5-carboxycytidine (5caC) in RNA.

Projecting the Combined Health Care Burden of Seasonal Influenza and COVID-19 in the 2020-2021 Season.

Unlabelled: In mid-2020, there was significant concern that the overlapping 2020-2021 influenza season and COVID-19 pandemic would overwhelm already stressed health care systems in the Northern Hemisphere, particularly if influenza immunization rates were low. Using a mathematical susceptible-exposed-infected-recovered (SEIR) compartmental model incorporating the age-specific viral transmission rates and disease severity of Austin, Texas, a large metropolitan region, we projected the incidence and health care burden for both COVID-19 and influenza across observed levels of SARS-CoV-2 transmission and influenza immunization rates for the 2020-2021 season. We then retrospectively compared scenario projections made in August 2020 with observed trends through June 2021.

A scoping review of the evidence for community-based dementia palliative care services and their related service activities.

Background: Palliative care is identified internationally as a priority for efficacious dementia care. Research into "effective models" of palliative care for people with dementia has been recommended by several European countries. To build an effective service-delivery model we must gain an understanding of existing models used in similar settings.

TRACEBACK: Testing of Historical Tubo-Ovarian Cancer Patients for Hereditary Risk Genes as a Cancer Prevention Strategy in Family Members.

Purpose: Tubo-ovarian cancer (TOC) is a sentinel cancer for and pathogenic variants (PVs). Identification of a PV in the first member of a family at increased genetic risk (the proband) provides opportunities for cancer prevention in other at-risk family members. Although Australian testing rates are now high, PVs in patients with TOC whose diagnosis predated revised testing guidelines might have been missed.

Scrotal Pain Caused by a Segmental Testicular Infarct.

Case Presentation: A 44-year-old Black male presented to the emergency department with left scrotal pain. His initial workup did not identify an etiology of his symptoms; however, he returned the following day with worsening pain and a radiology-performed ultrasound then revealed a segmental testicular infarct.

Discussion: Segmental testicular infarcts are a rare, often idiopathic, source of scrotal pain.

Assessment of photoacoustic tomography contrast for breast tissue imaging using 3D correlative virtual histology.

Current breast tumor margin detection methods are destructive, time-consuming, and result in significant reoperative rates. Dual-modality photoacoustic tomography (PAT) and ultrasound has the potential to enhance breast margin characterization by providing clinically relevant compositional information with high sensitivity and tissue penetration. However, quantitative methods that rigorously compare volumetric PAT and ultrasound images with gold-standard histology are lacking, thus limiting clinical validation and translation.

Tumour mutational burden: an overview for pathologists.

Cancer immunotherapy holds great promise and has shown durable responses in many patients; however, these responses are not uniform in all patients or all tumour streams. There is an ongoing clinical need for objective diagnostic biomarkers to identify patients that will respond to immunotherapies. Tumour mutational burden (TMB) is a diagnostic biomarker that can stratify cancer patients for response to immune checkpoint inhibitor therapies.

Special Issue on new therapeutic approaches to Parkinson disease.

Parkinson's disease (PD) is a common neurodegenerative disorder. Age is the biggest risk factor, with the prevalence rising from 1% in 45-54 year age group to 2-4% in 85 year or older. Population increases have led some to predict that we are facing a 'PD Pandemic' with the prevalence doubling in the next two decades.

Oral famotidine versus placebo in non-hospitalised patients with COVID-19: a randomised, double-blind, data-intense, phase 2 clinical trial.

Objective: We assessed whether famotidine improved inflammation and symptomatic recovery in outpatients with mild to moderate COVID-19.

Design: Randomised, double-blind, placebo-controlled, fully remote, phase 2 clinical trial (NCT04724720) enrolling symptomatic unvaccinated adult outpatients with confirmed COVID-19 between January 2021 and April 2021 from two US centres. Patients self-administered 80 mg famotidine (n=28) or placebo (n=27) orally three times a day for 14 consecutive days.

Impact of the Timing of Stay-at-Home Orders and Mobility Reductions on First-Wave COVID-19 Deaths in US Counties.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission continues to evolve, understanding the contribution of location-specific variations in nonpharmaceutical interventions and behaviors to disease transmission during the initial epidemic wave will be key for future control strategies. We offer a rigorous statistical analysis of the relative effectiveness of the timing of both official stay-at-home orders and population mobility reductions during the initial stage of the US coronavirus disease 2019 (COVID-19) epidemic. We used a Bayesian hierarchical regression to fit county-level mortality data from the first case on January 21, 2020, through April 20, 2020, and quantify associations between the timing of stay-at-home orders and population mobility with epidemic control.

Secondary Prevention Using Cholesterol-Lowering Medications in Patients with Prior Atherosclerotic Cardiovascular Disease Events: A Retrospective Cohort Analysis.

Secondary prevention with lipid-lowering medications in patients with atherosclerotic cardiovascular disease (ASCVD) is known to reduce the risk of clinical events and death. Current guidelines codify recommendations for implementing secondary prevention in appropriate patients. However, in real-world practice, secondary prevention is frequently initiated only after the patient experiences a cardiovascular-related hospitalization.

BMP3 is a novel locus involved in the causality of ocular coloboma.

Coloboma, a congenital disorder characterized by gaps in ocular tissues, is caused when the choroid fissure fails to close during embryonic development. Several loci have been associated with coloboma, but these represent less than 40% of those that are involved with this disease. Here, we describe a novel coloboma-causing locus, BMP3.