Cloning and Functional Characterization of Novel Human Neutralizing Anti-IFN-α and Anti-IFN-β Antibodies.

Type I IFNs play a pivotal role in immune response modulation, yet dysregulation is implicated in various disorders. Therefore, it is crucial to develop tools that facilitate the understanding of their mechanism of action and enable the development of more effective anti-IFN therapeutic strategies. In this study, we isolated, cloned, and characterized anti-IFN-α and anti-IFN-β Abs from PBMCs of individuals treated with IFN-α or IFN-β, harboring confirmed neutralizing Abs.

Cloning and functional characterization of novel human neutralizing anti-interferon-alpha and anti-interferon-beta antibodies.

Type I interferons (IFNs) play a pivotal role in immune response modulation, yet dysregulation is implicated in various disorders. Therefore, it is crucial to develop tools that facilitate the understanding of their mechanism of action and enable the development of more effective anti-IFN therapeutic strategies. In this study, we isolated, cloned, and characterized anti-IFN-α and anti-IFN-β antibodies (Abs) from peripheral blood mononuclear cells of individuals treated with IFN-α or IFN-β, harboring confirmed neutralizing Abs.

The In-Cell Western immunofluorescence assay to monitor PROTAC mediated protein degradation.

The In-Cell Western plate-based immunofluorescence assay is a useful methodology for monitoring protein levels and provides a facile moderate through-put method for PROTAC and degrader optimization. The method is compared to other reported assays used for PROTAC development. The advantages of this method are the greater through-put compared to Western blots due to its plate-based method and the ease to transfer between cells lines.

A Geographical Analysis of Access to Trauma Centers from US National Parks in 2018.

Introduction: Millions of people visit US national parks annually to engage in recreational wilderness activities, which can occasionally result in traumatic injuries that require timely, high-level care. However, no study to date has specifically examined timely access to trauma centers from national parks. This study aimed to examine the accessibility of trauma care from national parks by calculating the travel time by ground and air from each park to its nearest trauma center.

Development of a Unified National Database of Burn Centers With Colocated Emergency Departments, 2020.

The care of severely burned patients comes with unique requirements for specialized burn centers. The American Burn Association sets guidelines for burn centers and provides a voluntary program to verify their quality of care. However, not all burn centers are verified, and it is unclear which nonverified centers have met requirements set by their state health departments.

The Natural Stilbenoid (-)-Hopeaphenol Inhibits Cellular Entry of SARS-CoV-2 USA-WA1/2020, B.1.1.7, and B.1.351 Variants.

Antivirals are urgently needed to combat the global SARS-CoV-2/COVID-19 pandemic, supplement existing vaccine efforts, and target emerging SARS-CoV-2 variants of concern. Small molecules that interfere with binding of the viral spike receptor binding domain (RBD) to the host angiotensin-converting enzyme II (ACE2) receptor may be effective inhibitors of SARS-CoV-2 cell entry. Here, we screened 512 pure compounds derived from natural products using a high-throughput RBD/ACE2 binding assay and identified (-)-hopeaphenol, a resveratrol tetramer, in addition to vatalbinoside A and vaticanol B, as potent and selective inhibitors of RBD/ACE2 binding and viral entry.

Assembly of the Northern Cardinal () Genome Reveals Candidate Regulatory Regions for Sexually Dichromatic Red Plumage Coloration.

Northern cardinals () are common, mid-sized passerines widely distributed in North America. As an iconic species with strong sexual dichromatism, it has been the focus of extensive ecological and evolutionary research, yet genomic studies investigating the evolution of genotype-phenotype association of plumage coloration and dichromatism are lacking. Here we present a new, highly-contiguous assembly for We generated a 1.

If we cannot measure it, we cannot improve it: Understanding measurement problems in routine oral/dental assessments in Canadian nursing homes-Part II.

Objective: To evaluate the response process validity of the Resident Assessment Instrument-Minimum Data Set 2.0 (RAI) oral/dental items and the organisational processes for assessing nursing home (NH) residents' oral/dental status.

Background: Although care aides provide most direct care to NH residents, including oral care, they are not directly involved in structured care planning activities, including RAI assessments.

If we cannot measure it, we cannot improve it: Understanding measurement problems in routine oral/dental assessments in Canadian nursing homes-Part I.

Objective: To compare Resident Assessment Instrument-Minimum Data Set 2.0 (RAI) oral/dental items collected by nursing home (NH) care staff to (a) assessments collected by trained research assistants (RAs) and (b) "gold standard" clinical assessments by dental hygienists (DHs).

Background: Routine collection of RAI oral/dental items is mandatory in most Canadian NHs.

Pilot Trial of Adoptive Transfer of Chimeric Antigen Receptor-transduced T Cells Targeting EGFRvIII in Patients With Glioblastoma.

A deletion variant of epidermal growth factor receptor (EGFRvIII) is a known driver mutation in a subset of primary and secondary glioblastoma multiforme. Adoptive transfer of genetically modified chimeric antigen receptor (CAR) lymphocytes has demonstrated efficacy in hematologic malignancies but is still early in development for solid cancers. The surface expression of the truncated extracellular ligand domain created by EGFRvIII makes it an attractive target for a CAR-based cancer treatment.

Does Economic Strengthening Improve Viral Suppression Among Adolescents Living with HIV? Results From a Cluster Randomized Trial in Uganda.

To assess the effect of a savings-led economic empowerment intervention on viral suppression among adolescents living with HIV. Using data from Suubi + Adherence, a longitudinal, cluster randomized trial in southern Uganda (2012-2017), we examine the effect of the intervention on HIV RNA viral load, dichotomized between undetectable (< 40 copies/ml) and detectable (≥ 40 copies/ml). Cluster-adjusted comparisons of means and proportions were used to descriptively analyze changes in viral load between study arms while multi-level modelling was used to estimate treatment efficacy after adjusting for fixed and random effects.

HIV Risk Among Displaced Adolescent Girls in Ethiopia: the Role of Gender Attitudes and Self-Esteem.

Adolescent girls in sub-Saharan Africa have been deemed one of the most critical populations to address in the campaign for an HIV-free generation. Experiences of intimate partner violence (IPV), harmful gender norms, diminished personal agency, and age-disparate sex have been identified as factors in the increasing rate of new infections among this population. Using baseline data from a cluster-randomized controlled trial in three refugee camps in Benishangul-Gumuz Regional State in Ethiopia, our study quantitatively examined the associations between HIV risk factors, attitudes on gender inequality, IPV acceptability, and self-esteem for female adolescent refugees primarily from Sudan and South Sudan (n = 919).

Predictors of Interpersonal Violence in the Household in Humanitarian Settings: A Systematic Review.

Interpersonal violence against women and children has increasingly been recognized as a public health priority in humanitarian emergencies. However, because the household is generally considered a private sphere, violence between family members remains neglected. A systematic literature review was conducted to identify predictors of household violence in humanitarian emergencies.

Characterization of an Immunogenic Mutation in a Patient with Metastatic Triple-Negative Breast Cancer.

The administration of autologous tumor-infiltrating lymphocytes (TILs) can mediate durable tumor regressions in patients with melanoma likely based on the recognition of immunogenic somatic mutations expressed by the cancer. There are limited data regarding the immunogenicity of mutations in breast cancer. We sought to identify immunogenic nonsynonymous mutations in a patient with triple-negative breast cancer (TNBC) to identify and isolate mutation-reactive TILs for possible use in adoptive cell transfer.

A safety and pharmacokinetic dosing study of glucagon-like peptide 2 in infants with intestinal failure.

Background & Aims: Glucagon-like peptide 2 (GLP-2) analogues are approved for adults with intestinal failure (IF), but no studies have included infants. This study examined the pharmacokinetics (PK), safety, and nutritional effects of GLP-2 in infants with IF.

Methods: With parental consent (Health Canada Protocol:150,979), parenteral nutrition (PN)-dependent infants were treated with 5-20-μg/kg/day GLP-2 for 3days (phase 1), and if tolerated continued for 42days (phase 2).

Von Willebrand factor regulates complement on endothelial cells.

Atypical hemolytic uremic syndrome and thrombotic thrombocytopenic purpura have traditionally been considered separate entities. Defects in the regulation of the complement alternative pathway occur in atypical hemolytic uremic syndrome, and defects in the cleavage of von Willebrand factor (VWF)-multimers arise in thrombotic thrombocytopenic purpura. However, recent studies suggest that both entities are related as defects in the disease-causing pathways overlap or show functional interactions.

Randomized, Prospective Evaluation Comparing Intensity of Lymphodepletion Before Adoptive Transfer of Tumor-Infiltrating Lymphocytes for Patients With Metastatic Melanoma.

Purpose: Adoptive cell transfer, the infusion of large numbers of activated autologous lymphocytes, can mediate objective tumor regression in a majority of patients with metastatic melanoma (52 of 93; 56%). Addition and intensification of total body irradiation (TBI) to the preparative lymphodepleting chemotherapy regimen in sequential trials improved objective partial and complete response (CR) rates. Here, we evaluated the importance of adding TBI to the adoptive transfer of tumor-infiltrating lymphocytes (TIL) in a randomized fashion.

Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia.

Some familial platelet disorders are associated with predisposition to leukemia, myelodysplastic syndrome (MDS) or dyserythropoietic anemia. We identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B cell-precursor acute lymphoblastic leukemia (ALL). Whole-exome sequencing identified a heterozygous single-nucleotide change in ETV6 (ets variant 6), c.

MATR3 disruption in human and mouse associated with bicuspid aortic valve, aortic coarctation and patent ductus arteriosus.

Cardiac left ventricular outflow tract (LVOT) defects represent a common but heterogeneous subset of congenital heart disease for which gene identification has been difficult. We describe a 46,XY,t(1;5)(p36.11;q31.

Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor.

Purpose: T cells can be genetically modified to express an anti-CD19 chimeric antigen receptor (CAR). We assessed the safety and efficacy of administering autologous anti-CD19 CAR T cells to patients with advanced CD19(+) B-cell malignancies.

Patients And Methods: We treated 15 patients with advanced B-cell malignancies.

Myeloid-derived suppressor cells in the development of lung cancer.

Myeloid-derived suppressor cells (MDSC) are widely implicated in immune suppression associated with tumor progression and chronic inflammation. However, very little is known about their possible role in tumor development. Here, we evaluated the role of MDSC in two experimental models of lung cancer: inflammation-associated lung cancer caused by chemical carcinogen urethane in combination with exposure to cigarette smoke; and a transgenic CC10Tg model not associated with inflammation.

Eculizumab therapy in children with severe hematopoietic stem cell transplantation-associated thrombotic microangiopathy.

We recently observed that dysregulation of the complement system may be involved in the pathogenesis of hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA). These findings suggest that the complement inhibitor eculizumab could be a therapeutic option for this severe HSCT complication with high mortality. However, the efficacy of eculizumab in children with HSCT-TMA and its dosing requirements are not known.

FG7142, yohimbine, and βCCE produce anxiogenic-like effects in the elevated plus-maze but do not affect brainstem activated hippocampal theta.

The neurobiological underpinnings of anxiety are of paramount importance to selective and efficacious pharmaceutical intervention. Hippocampal theta frequency in urethane anaesthetized rats is suppressed by all known (and some previously unknown) anti-anxiety (anxiolytic) drugs. Although these findings support the predictive validity of this assay, its construct validity (i.