Functional validation of a novel STAT3 'variant of unknown significance' identifies a new case of STAT3 GOF Syndrome and reveals broad immune cell defects.

Introduction: STAT3 orchestrates crucial immune responses through its pleiotropic functions as a transcription factor. Patients with germline monoallelic dominant negative or hypermorphic STAT3 variants, who present with immunodeficiency and/or immune dysregulation, have revealed the importance of balanced STAT3 signaling in lymphocyte differentiation and function, and immune homeostasis. Here, we report a novel missense variant of unknown significance in the DNA binding domain of STAT3 in a patient who experienced hypogammaglobulinemia, lymphadenopathy, hepatosplenomegaly, immune thrombocytopenia, eczema and enteropathy over a 35-year period.

A Novel Case of IFNAR1 Deficiency Identified a Common Canonical Splice Site Variant in DOCK8 in Western Polynesia: The Importance of Validating Variants of Unknown Significance in Under-Represented Ancestries.

Advanced genomic technologies such as whole exome or whole genome sequencing have improved diagnoses and disease outcomes for individuals with genetic diseases. Yet, variants of unknown significance (VUS) require rigorous validation to establish disease causality or modification, or to exclude them from further analysis. Here, we describe a young individual of Polynesian ancestry who in the first 13 mo of life presented with SARS-CoV-2 pneumonia, severe enterovirus meningitis and adenovirus gastroenteritis, and severe adverse reaction to MMR vaccination.

Formation of Products of Incomplete Destruction (PID) from the Thermal Oxidative Decomposition of Perfluorooctanoic Acid (PFOA): Measurement, Modeling, and Reaction Pathways.

The thermal decomposition of perfluorooctanoic acid (PFOA) under oxidative conditions was investigated using air (O) and NO as oxidants over temperatures ranging from 400 to 1000 °C in an α-alumina reactor. In the presence of air, PFOA was found to decompose into perfluorohept-1-ene (CF) and perfluoroheptanoyl fluoride (CFO) in addition to HF, CO, and CO. At temperatures above 800 °C, both CF and CFO were no longer detected.

Radioactive waste microbiology: predicting microbial survival and activity in changing extreme environments.

The potential for microbial activity to occur within the engineered barrier system (EBS) of a geological disposal facility (GDF) for radioactive waste is acknowledged by waste management organizations as it could affect many aspects of the safety functions of a GDF. Microorganisms within an EBS will be exposed to changing temperature, pH, radiation, salinity, saturation, and availability of nutrient and energy sources, which can limit microbial survival and activity. Some of the limiting conditions are incorporated into GDF designs for safety reasons, including the high pH of cementitious repositories, the limited pore space of bentonite-based repositories, or the high salinity of GDFs in evaporitic geologies.

The trajectory of human B-cell function, immune deficiency, and allergy revealed by inborn errors of immunity.

The essential role of B cells is to produce protective immunoglobulins (Ig) that recognize, neutralize, and clear invading pathogens. This results from the integration of signals provided by pathogens or vaccines and the stimulatory microenvironment within sites of immune activation, such as secondary lymphoid tissues, that drive mature B cells to differentiate into memory B cells and antibody (Ab)-secreting plasma cells. In this context, B cells undergo several molecular events including Ig class switching and somatic hypermutation that results in the production of high-affinity Ag-specific Abs of different classes, enabling effective pathogen neutralization and long-lived humoral immunity.

Cutaneous lesions and clinical outcomes in five cats after frunevetmab injections.

Case Series Summary: This case series describes five cats with cutaneous adverse events after subcutaneous administration of frunevetmab, a felinised anti-nerve growth factor monoclonal antibody, including histopathological findings in one case. All cats displayed moderate to severe pruritus resulting in self-trauma to the neck and/or head, causing lesions ranging from superficial dermatitis to alopecia and ulcerations. There were no reactions at the injection sites.

Influence of reactor composition on the thermal decomposition of perfluorooctanesulfonic acid (PFOS).

Various reactor tubes (quartz, stainless steel 316 and stainless steel 253 MA) were used to examine their influence on the thermal decomposition of perfluorooctanesulfonic acid (PFOS) between 400 and 1000 °C. Using helium as a carrier gas, with the addition of 100 - 300 ppm of PFOS to the feed gas, the influence of the reactor materials on PFOS decomposition was studied. The quartz reactor led to a notable reduction in the concentration of HF and substantial quantities of SiF were observed.

Genome Characterisation of the CGMMV Virus Population in Australia-Informing Plant Biosecurity Policy.

The detection of cucumber green mottle mosaic (CGMMV) in the Northern Territory (NT), Australia, in 2014 led to the introduction of strict quarantine measures for the importation of cucurbit seeds by the Australian federal government. Further detections in Queensland, Western Australia (WA), New South Wales and South Australia occurred in the period 2015-2020. To explore the diversity of the current Australian CGMMV population, 35 new coding sequence complete genomes for CGMMV isolates from Australian incursions and surveys were prepared for this study.

Metastatic Anaplastic Sarcoma in a Wild Lace Monitor (Varanus varius).

A wild lace monitor, Varanus varius, was euthanized due to an inoperable malignant anaplastic sarcoma that resembled hemangiosarcoma. Histopathologic examination identified metastatic spread to the lung, heart, and liver.

The ups and downs of STAT3 function: too much, too little and human immune dysregulation.

The STAT3 story has almost 30 years of evolving history. First identified in 1994 as a pro-inflammatory transcription factor, Signal Transducer and Activator of Transcription 3 (STAT3) has continued to be revealed as a quintessential pleiotropic signalling module spanning fields including infectious diseases, autoimmunity, vaccine responses, metabolism, and malignancy. In 2007, germline heterozygous dominant-negative loss-of-function variants in STAT3 were discovered as the most common cause for a triad of eczematoid dermatitis with recurrent skin and pulmonary infections, first described in 1966.

Personas of pregnant and parenting women with substance use and their barriers and pathways to system engagement.

Background: Women with prenatal substance use have been identified as at-risk for the lack of engagement in perinatal services, such as medical care and home visitation programs. This issue is of particular concern in Florida (United States) where rates of fetal substance exposure have been steadily increasing.

Methods: To identify pathways of and barriers to perinatal system and service engagement, journey mapping was used to compile various personas of perinatal women with substance use.

Targeted Whole Genome Sequencing (TWG-Seq) of Cucumber Green Mottle Mosaic Virus Using Tiled Amplicon Multiplex PCR and Nanopore Sequencing.

Rapid and reliable detection tools are essential for disease surveillance and outbreak management, and genomic data is essential to determining pathogen origin and monitoring of transmission pathways. Low virus copy number and poor RNA quality can present challenges for genomic sequencing of plant viruses, but this can be overcome by enrichment of target nucleic acid. A targeted whole genome sequencing (TWG-Seq) approach for the detection of cucumber green mottle mosaic virus (CGMMV) has been developed where overlapping amplicons generated using two multiplex RT-PCR assays are then sequenced using the Oxford Nanopore MinION.

Mosaic embryo transfer-first report of a live born with nonmosaic partial aneuploidy and uniparental disomy 15.

Objective: To inform clinicians of the first known case of a live born diagnosed with syndromic partial trisomy 15 and maternal uniparental disomy 15 resulting from a mosaic embryo transfer (MET). We believe that this case will highlight the need for standardized practice guidelines to address the potential risk of MET and the importance of prenatal follow-up after a pregnancy is achieved from a MET.

Design: Case report.

Human gut bifidobacteria inhibit the growth of the opportunistic fungal pathogen Candida albicans.

The human gut microbiota protects the host from invading pathogens and the overgrowth of indigenous opportunistic species via a process called colonization resistance. Here, we investigated the antagonistic activity of human gut bacteria towards Candida albicans, an opportunistic fungal pathogen that can cause severe infections in susceptible individuals. Coculture batch incubations of C.

STAT5B restrains human B-cell differentiation to maintain humoral immune homeostasis.

Background: Lymphocyte differentiation is regulated by coordinated actions of cytokines and signaling pathways. IL-21 activates STAT1, STAT3, and STAT5 and is fundamental for the differentiation of human B cells into memory cells and antibody-secreting cells. While STAT1 is largely nonessential and STAT3 is critical for this process, the role of STAT5 is unknown.

A New Real-Time PCR Assay for Detecting Fungi in Genus .

The genus contains several significant plant pathogens, causing wilt and canker disease on a wide range of plant species. There are >40 known species of , some of which are becoming increasingly important in agricultural or natural ecosystems. The diagnostic procedures for most species rely on time-consuming and labor-intensive culturing approaches.

Human STAT3 variants underlie autosomal dominant hyper-IgE syndrome by negative dominance.

Most patients with autosomal dominant hyper-IgE syndrome (AD-HIES) carry rare heterozygous STAT3 variants. Only six of the 135 in-frame variants reported have been experimentally shown to be dominant negative (DN), and it has been recently suggested that eight out-of-frame variants operate by haploinsufficiency. We experimentally tested these 143 variants, 7 novel out-of-frame variants found in HIES patients, and other STAT3 variants from the general population.

Carbon dioxide laser surgery for chronic proliferative and obstructive otitis externa in 26 dogs.

Background: Some dogs with chronic otitis externa (OE) develop proliferation of the tissues surrounding the opening of the external ear canal, resulting in obstruction. Traditionally total ear canal ablation with bulla osteotomy (TECABO) has been recommended.

Objectives: To evaluate the efficacy of a novel treatment using carbon dioxide (CO ) laser surgery and to describe the histopathological features of chronic proliferative and obstructive OE.

MICROSPORIDIA-ASSOCIATED GRANULOMATOUS DISEASE IN TWO AUSTRALIAN COLLECTIONS OF CAPTIVE INLAND BEARDED DRAGONS ().

Microsporidia are obligate, intracellular fungi. In reptiles, they are most commonly reported in squamates. We report the first detection of microsporidiosis in inland bearded dragons () from Australia, and for the first time, mixed infections of microsporidium and adenovirus in asymptomatic inland bearded dragons.

A survey of Canadian radiation therapists' perspectives on caring for LGBTQ2SPIA+ cancer patients.

Purpose: The lesbian, gay, bisexual, trans, queer, two-spirit, pansexual, intersex, asexual, plus (LGBTQ2SPIA+) population faces unique cancer health risks and barriers to competent healthcare. This study aimed to identify current knowledge, attitudes, and practice behaviours amongst radiation therapists regarding the LGBTQ2SPIA+ community to ultimately improve care given to this population.

Methods: A 22-item online survey was sent out to Canadian radiation therapy department managers and forwarded to radiation therapists.

Products and mechanism of thermal decomposition of chlorpyrifos under inert and oxidative conditions.

Chlorpyrifos (CPF) is a widely used pesticide; however, limited experimental work has been completed on its thermal decomposition. CPF is known to decompose into 3,5,6-trichloro-2-pyridinol (TCpyol) together with ethylene and HOPOS. Under oxidative conditions TCpyol can decompose into the dioxin-like 2,3,7,8-tetrachloro-[1,4]-dioxinodipyridine (TCDDPy).

Mid-term follow-up after aortic valve replacement with the Carpentier Edwards Magna Ease prosthesis.

Background: Approximately 250,000 heart valve operations are performed annually worldwide. An intensive research and development effort has led to progressively more advanced heart valve prostheses. The Carpentier-Edwards Perimount Magna Ease (CEPME) prosthesis represents the latest iteration of the Edwards Perimount series of aortic tissue valves.