BATMAN: Improved T cell receptor cross-reactivity prediction benchmarked on a comprehensive mutational scan database.

Predicting T cell receptor (TCR) activation is challenging due to the lack of both unbiased benchmarking datasets and computational methods that are sensitive to small mutations to a peptide. To address these challenges, we curated a comprehensive database encompassing complete single amino acid mutational assays of 10,750 TCR-peptide pairs, centered around 14 immunogenic peptides against 66 TCRs. We then present an interpretable Bayesian model, called BATMAN, that can predict the set of peptides that activates a TCR.

Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever.

Infection with Lassa virus (LASV) can cause Lassa fever, a haemorrhagic illness with an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity of LASV infection, we carried out genome-wide association studies (GWAS) as well as seroprevalence surveys, human leukocyte antigen typing and high-throughput variant functional characterization assays.

copepodTCR: Identification of Antigen-Specific T Cell Receptors with combinatorial peptide pooling.

T cell receptor (TCR) repertoire diversity enables the orchestration of antigen-specific immune responses against the vast space of possible pathogens. Identifying TCR/antigen binding pairs from the large TCR repertoire and antigen space is crucial for biomedical research. Here, we introduce , an open-access tool for the design and interpretation of high-throughput experimental assays to determine TCR specificity.

Association between statin exposure and short-term mortality in patients with high-grade acute-on-chronic liver failure.

Background & Aims: Acute-on-chronic liver failure (ACLF) carries a high short-term mortality for patients with cirrhosis. Prior literature suggests that statin exposure may reduce the likelihood of ACLF events. However, it is unclear if statin exposure is associated with ACLF-related mortality.

Built On-orbit Robotically assembled Gigatruss (BORG): A mixed assembly architecture trade study.

This paper explores a mixed assembly architecture trade study for a Built On-orbit Robotically assembled Gigatruss (BORG). Robotic in-space assembly (ISA) and servicing is a crucial field to expand endeavors in space. Currently, large structures in space are commonly only deployable and must be efficiently folded and packed into a launch vehicle (LV) and then deployed perfectly for operational status to be achieved.

Insecticidal activity of Simparica and Simparica Trio against Aedes aegypti in dogs.

Background: Aedes aegypti is one of the main species responsible for the transmission of mosquito-borne pathogens worldwide. The isoxazoline Sarolaner has excellent efficacy as an acaricide against ticks and mites and as an insecticide against fleas, and potential efficacy against other insects.

Methods: In each of two laboratory studies, 24 dogs were randomly allocated (n = 8/group) to an untreated control group, a Simparica-treated group (at the minimum dose of 2.

Transcriptomic diversity in human medullary thymic epithelial cells.

The induction of central T cell tolerance in the thymus depends on the presentation of peripheral self-epitopes by medullary thymic epithelial cells (mTECs). This promiscuous gene expression (pGE) drives mTEC transcriptomic diversity, with non-canonical transcript initiation, alternative splicing, and expression of endogenous retroelements (EREs) representing important but incompletely understood contributors. Here we map the expression of genome-wide transcripts in immature and mature human mTECs using high-throughput 5' cap and RNA sequencing.

Immune-stimulating antibody conjugates elicit robust myeloid activation and durable antitumor immunity.

Innate pattern recognition receptor agonists, including Toll-like receptors (TLRs), alter the tumor microenvironment and prime adaptive antitumor immunity. However, TLR agonists present toxicities associated with widespread immune activation after systemic administration. To design a TLR-based therapeutic suitable for systemic delivery and capable of safely eliciting tumor-targeted responses, we developed immune-stimulating antibody conjugates (ISACs) comprising a TLR7/8 dual agonist conjugated to tumor-targeting antibodies.

Statin exposure is associated with reduced development of acute-on-chronic liver failure in a Veterans Affairs cohort.

Backgrounds & Aims: There is a need to identify therapies that prevent the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis. This study sought to evaluate the association between statin exposure and the risk of developing ACLF in a large national cohort of patients with cirrhosis.

Methods: We performed a retrospective cohort study of patients diagnosed with cirrhosis within the Veterans Health Administration from 2008 and 2018.

External Validation of the FIPS Score for Post-TIPS Mortality in a National Veterans Affairs Cohort.

Background: The Freiburg index of post-TIPS survival (FIPS) score was recently demonstrated to improve prediction of post-TIPS mortality relative to existing standards. As this score was derived from a German cohort over an extended time period, it is unclear if performance will translate well to other settings. This study aimed to externally validate the FIPS score in a large Veterans Affairs (VA) cohort over two separate eras of TIPS-related care.

The effects of AAC video visual scene display technology on the communicative turns of preschoolers with autism spectrum disorder.

Over 40% of children with autism spectrum disorder (ASD) experience difficulty in using speech to meet their daily communication needs. Although augmentative and alternative communication (AAC) can be of benefit, the AAC intervention must support beginning communicators in the early social interactions that provide the foundation for more sophisticated communication skills. An AAC video visual scene display approach uses an AAC app (provided on a tablet computer), including videos based on the interests of the child and infused with AAC supports, to provide opportunities for social interaction and communication between the child and the communication partner.

Evaluation of Risk Factors for Hepatitis C Virus Infection Among Philadelphia's Shelter-Bound, Homeless Population: Data from a Student-Run Hepatitis C Virus Screening Initiative.

The objective was to assess risk factors for HCV specific to the shelter-bound homeless population of Philadelphia, Pennsylvania. This is a retrospective analysis of data obtained from 306 patients who received HCV antibody testing at 4 homeless shelters in Philadelphia between March 2017 and June 2019. Risk factors for HCV infection specific to this population were analyzed using Fischer exact tests.

The Effects of Shared e-Book Reading With Dynamic Text and Speech Output on the Single-Word Reading Skills of Young Children With Developmental Disabilities.

Purpose This study investigated the use of a new software feature, namely, dynamic text with speech output, on the acquisition of single-word reading skills by six children with developmental disabilities during shared e-book reading experiences with six typically developing peers. Method A single-subject, multiple-probe design across participants was used to evaluate the effects of the software intervention. Six children with developmental delays were the primary focus for intervention, while six children with typical development participated as peer partners in intervention activities.

Breast carcinoma metastasis in a resected meningioma with early diagnosis of oligometastatic disease: a case report.

Tumor-to-tumor metastasis describes the ability of primary tumors to metastasize to other primary tumors. These events generally occur in aggressive and widely-metastatic disease, with the appropriate management and significance of these events unknown. A 56-year-old woman with a history of bilateral, localized, invasive lobular breast carcinoma treated with surgery, systemic therapy, and adjuvant radiation presented five and two years post-treatment with progressive neurological symptoms.

Efficacy of a novel orally administered combination product containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced infestations of five common tick species infesting dogs in the USA.

Background: The efficacy of a novel oral combination product, Simparica Trio™, containing sarolaner, moxidectin and pyrantel was evaluated against five tick species that commonly infest dogs in the USA, Amblyomma americanum, Amblyomma maculatum, Dermacentor variabilis, Ixodes scapularis and Rhipicephalus sanguineus.

Methods: Laboratory studies were conducted against two different strains of each tick species. In each study, 10 purpose-bred Beagle or mixed-breed dogs were randomly allocated to one of two treatment groups based on pre-treatment host-suitability tick counts.

Laboratory studies evaluating the efficacy of a novel orally administered combination product containing sarolaner, moxidectin and pyrantel (Simparica Trio™) for the treatment and control of flea infestations on dogs.

Background: Five studies were conducted to evaluate a novel oral combination tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™), for efficacy against induced flea infestations, speed of kill and effects on flea reproduction on dogs.

Methods: Based on pre-treatment flea counts, dogs were randomly allocated to treatment with a single, oral dose of either placebo or Simparica Trio™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) on Day 0.

Transnational corporations and the challenge of biosphere stewardship.

Sustainability within planetary boundaries requires concerted action by individuals, governments, civil society and private actors. For the private sector, there is concern that the power exercised by transnational corporations generates, and is even central to, global environmental change. Here, we ask under which conditions transnational corporations could either hinder or promote a global shift towards sustainability.

Laboratory and field studies to investigate the efficacy of a novel, orally administered combination product containing moxidectin, sarolaner and pyrantel for the prevention of heartworm disease (Dirofilaria immitis) in dogs.

Background: Dirofilaria immitis is a filarial parasite of dogs that can cause serious or fatal cardiopulmonary disease. Three studies were conducted to evaluate the efficacy and safety of monthly treatment with moxidectin in a chewable tablet product in combination with sarolaner and pyrantel to prevent heartworm disease in dogs after experimental challenge and in a clinical field study in the USA.

Methods: In two laboratory studies, dogs (8 per group) that had been inoculated 30 days prior with 50 third-stage D.

Preventive efficacy of oral moxidectin at various doses and dosage regimens against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs.

Background: Moxidectin has previously shown limited efficacy (≤ 44.4%) against confirmed macrocyclic lactone (ML)-resistant Dirofilaria immitis strains at 3 µg/kg after single and multiple oral dosages. Three studies were conducted to evaluate higher oral moxidectin doses for efficacy against confirmed ML-resistant D.

Efficacy of three consecutive monthly doses of a topical formulation of selamectin and sarolaner (Revolution Plus/Stronghold Plus) compared with a single dose of fluralaner (Bravecto for Cats) against induced infestations of Ctenocephalides felis on cats.

In a controlled laboratory study, the efficacy against fleas, Ctenocephalides felis, of a single treatment of fluralaner topical solution (Bravecto for Cats, Merck) was compared with that of three consecutive monthly topical treatments with selamectin and sarolaner (Revolution Plus, Zoetis). Twenty-four domestic short hair cats were ranked based on host suitability flea counts to form groups of three and were randomly assigned within group to one of three treatments. The first group received a topical treatment with (a) placebo (vehicle control for Revolution Plus) on Days 0, 30, and 60, (b) 6 mg/kg selamectin and 1 mg/kg sarolaner on Days 0, 30, and 60, or (c) 40 mg/kg fluralaner on Day 0 and placebo (vehicle control for Revolution Plus) on Days 30 and 60.

Efficacy and safety of a combination of selamectin plus sarolaner for the treatment and prevention of flea infestations and the treatment of ear mites in cats presented as veterinary patients in the United States.

Two randomised, single-masked, multi-center field studies were conducted in the United States in cats presented as veterinary patients. The first study evaluated the efficacy and safety of a topically applied formulation of selamectin plus sarolaner (Revolution Plus/Stronghold Plus, Zoetis) against natural flea infestations; the second study evaluated its efficacy against natural ear mite infestations. The product was administered topically by the cats' owners at the dose range provided in the market product of 6.

Efficacy of a new topical formulation containing selamectin plus sarolaner against three common tick species infesting cats in the United States.

The efficacy of a single topical application of a combination product containing selamectin and sarolaner (selamectin/sarolaner; Revolution Plus/Stronghold Plus) was evaluated in seven laboratory studies against Ixodes scapularis (three studies), Dermacentor variabilis (two studies), or Amblyomma maculatum (two studies). In each study, cats were randomly allocated to treatment groups based on pre-treatment host-suitability tick counts. On Days -2, 5, 12, 19, 26 and 33, the cats were infested with unfed adult ticks.