Improvement of variant reclassification in genetic neurodevelopmental conditions.

Purpose: Limited knowledge about disease mechanisms, few published cases, and the lack of functional assessment of variants for neurodevelopmental genetic disorders challenge diagnostic classification for variants and increase the frequency of variants of uncertain significance (VUS). Because inheritance patterns aid in variant interpretation for neurodevelopmental conditions, genetic testing including only the proband leads to larger numbers of VUS than testing strategies that include the parents.

Methods: We reinterpreted genetic variants submitted to the Simons Searchlight research registry using American College of Medical Genetics and Genomics variant interpretation guidelines, familial cascade testing, and literature curation with annual VUS reevaluation.

Evaluation of Needles in Endoscopic Ultrasound-Guided Tissue Acquisition of Pancreatic Cancer for Genetic Yield and Quality.

Background: Endoscopic ultrasound-guided fine needle biopsy (FNB) is the gold standard in tissue acquisition of pancreatic ductal adenocarcinoma (PDAC). There is a paucity of evidence of the impact of needle type or size on the genetic yield and quality.

Methods: Patients 18 years and older with PDAC who underwent FNB were retrospectively identified from a single database from 2016 to 2021.

Cytomegalovirus vaccine vector-induced effector memory CD4 + T cells protect cynomolgus macaques from lethal aerosolized heterologous avian influenza challenge.

An influenza vaccine approach that overcomes the problem of viral sequence diversity and provides long-lived heterosubtypic protection is urgently needed to protect against pandemic influenza viruses. Here, to determine if lung-resident effector memory T cells induced by cytomegalovirus (CMV)-vectored vaccines expressing conserved internal influenza antigens could protect against lethal influenza challenge, we immunize Mauritian cynomolgus macaques (MCM) with cynomolgus CMV (CyCMV) vaccines expressing H1N1 1918 influenza M1, NP, and PB1 antigens (CyCMV/Flu), and challenge with heterologous, aerosolized avian H5N1 influenza. All six unvaccinated MCM died by seven days post infection with acute respiratory distress, while 54.

No evidence for enhanced disease with human polyclonal SARS-CoV-2 antibody in the ferret model.

Since SARS-CoV-2 emerged in late 2019, it spread from China to the rest of the world. An initial concern was the potential for vaccine- or antibody-dependent enhancement (ADE) of disease as had been reported with other coronaviruses. To evaluate this, we first developed a ferret model by exposing ferrets to SARS-CoV-2 by either mucosal inoculation (intranasal/oral/ocular) or inhalation using a small particle aerosol.

Culinary continuity in central Japan across the transition to agriculture.

Unlabelled: Rice and millet arrived in Western Japan from Korea around 3,000 years ago and spread eastwards across the archipelago in the next 700 years. However, the extent to which agriculture transformed traditional Jōmon hunter-gatherer-fisher communities is debated. Central Japan is a key area of study as remodelling of radiocarbon dates shows a slowdown in the dispersal rate of rice agriculture in this area.

A Humanized Patient-Derived Xenograft Model for Pancreatic Cancer.

Pancreatic cancer is associated with a high mortality rate, and there are still very few effective treatment options. Patient-derived xenografts have proven to be invaluable preclinical disease models to study cancer biology and facilitate testing of novel therapeutics. However, the severely immune-deficient mice used to generate standard models lack any functional immune system, thereby limiting their utility as a tool to investigate the tumor-immune cell interface.

The impact of farming on prehistoric culinary practices throughout Northern Europe.

To investigate changes in culinary practices associated with the arrival of farming, we analysed the organic residues of over 1,000 pottery vessels from hunter-gatherer-fisher and early agricultural sites across Northern Europe from the Lower Rhine Basin to the Northeastern Baltic. Here, pottery was widely used by hunter-gatherer-fishers prior to the introduction of domesticated animals and plants. Overall, there was surprising continuity in the way that hunter-gatherer-fishers and farmers used pottery.

Circulating Tumor DNA Is an Accurate Diagnostic Tool and Strong Prognostic Marker in Pancreatic Cancer.

Objective: The objectives of the study are to investigate the sensitivity and specificity of circulating tumor DNA (ctDNA) for the diagnosis of pancreatic cancer and to assess the utility of ctDNA as a prognostic marker in this disease.

Methods: Cell-free DNA was extracted from plasma of patients who underwent endoscopic ultrasound fine-needle aspiration or surgical resections for pancreatic cancer. The cell-free DNA was then analyzed using droplet digital polymerase chain reaction for KRAS G12/13 mutations.

Transchromosomic bovine-derived anti-SARS-CoV-2 polyclonal human antibodies protects hACE2 transgenic hamsters against multiple variants.

Pandemic SARS-CoV-2 has undergone rapid evolution resulting in the emergence of many variants with mutations in the spike protein, some of which appear to evade antibody neutralization, transmit more efficiently, and/or exhibit altered virulence. This raises significant concerns regarding the efficacy of anti-S monoclonal antibody-based therapeutics which have failed against variant SARS-CoV-2 viruses. To address this concern, SAB-185, a human anti-SARS-CoV-2 polyclonal antibody was generated in the DiversitAb platform.

Endoscopic Ultrasound-Guided Fine-Needle Biopsies to Generate Preclinical Disease Models to Study Inflammation in Pancreatic Ductal Adenocarcinoma.

Patient-derived xenografts (PDXs) are valuable models to study cancer biology, behavior, and response to therapies in vivo. Pancreatic cancer is an aggressive and treatment-resistant disease, and typical biopsies are often of low cellular yield and therefore present challenges for the creation of PDXs. This chapter will describe a method to establish PDX models from tissue biopsies obtained via endoscopic ultrasound-guided fine-needle aspiration, a relatively noninvasive technique which compared to surgery is available to pancreatic cancer patients at all stages of disease.

Relationship between circulating tumour DNA and skeletal muscle stores at diagnosis of pancreatic ductal adenocarcinoma: a cross-sectional study.

Low skeletal muscle index (SMI) and low skeletal muscle radiodensity (SMD) are associated with reduced survival time in pancreatic ductal adenocarcinoma (PDAC). The negative prognostic impact of low SMI and low SMD is often reported as independent of cancer stage when using traditional clinical staging tools. Therefore, this study sought to explore the relationship between a novel marker of tumour burden (circulating tumour DNA) and skeletal muscle abnormalities at diagnosis of PDAC.

Detection of dairy products from multiple taxa in Late Neolithic pottery from Poland: an integrated biomolecular approach.

The detection of dairy processing is pivotal to our understanding of ancient subsistence strategies. This culinary process is linked to key arguments surrounding the evolution of lactase persistence in prehistory. Despite extensive evidence indicating the presence of dairy products in ceramics in the European Neolithic, questions remain about the nature and extent of milk (and lactose) processing and consumption.

Cuisine in transition? Organic residue analysis of domestic containers from 9th-14th century Sicily.

From the 9th to 14th centuries AD, Sicily experienced a series of rapid and quite radical changes in political regime, but the impact of these regime changes on the lives of the people that experienced them remains largely elusive within the historical narrative. We use a multi-faceted lipid residue approach to give direct chemical evidence of the use of 248 everyday domestic ceramic containers from Islamic and post-Islamic contexts in western Sicily to aid our understanding of daily habits throughout this period of political change. A range of commodities was successfully identified, including animal fats, vegetable products, fruit products (potentially including wine) and plant resins.

G12D Mutation Subtype in Pancreatic Ductal Adenocarcinoma: Does It Influence Prognosis or Stage of Disease at Presentation?

: G12D mutation subtype is present in over 40% of pancreatic ductal adenocarcinoma (PDAC), one of the leading global causes of cancer death. This retrospective cohort study aims to investigate whether detection of the G12D mutation subtype in PDAC patients is a determinant of prognosis across all stages of disease. : We reviewed the medical records of 231 patients presenting with PDAC at a large tertiary hospital, and compared survival using the Kaplan Meier, log-rank test and Cox proportional hazards regression model.

Blockade of the protease ADAM17 ameliorates experimental pancreatitis.

Acute and chronic pancreatitis, the latter associated with fibrosis, are multifactorial inflammatory disorders and leading causes of gastrointestinal disease-related hospitalization. Despite the global health burden of pancreatitis, currently, there are no effective therapeutic agents. In this regard, the protease A Disintegrin And Metalloproteinase 17 (ADAM17) mediates inflammatory responses through shedding of bioactive inflammatory cytokines and mediators, including tumor necrosis factor α (TNFα) and the soluble interleukin (IL)-6 receptor (sIL-6R), the latter of which drives proinflammatory IL-6 trans-signaling.

Comparisons of Cognitive Stimulation Therapy Between Community Versus Hospital-Based Settings: A Multi-Site Study.

Background: Non-pharmacological interventions such as Cognitive Stimulation Therapy (CST) have been shown to help persons living with dementia in improving cognitive function and recall. While previous CST interventions have been conducted largely with community populations, none have explored the outcomes of CST in larger healthcare settings. Our study explored differences of cognitive function, mood, and quality-of-life from CST groups both community and residential-based groups.

Emphysematous osteomyelitis of the calcaneus: a case report and review.

Emphysematous osteomyelitis is a rare but potentially fatal condition, which classically features intraosseous air on imaging without a direct communication with the atmosphere. Prompt recognition and treatment of the disease cannot be overstated as there is a high mortality rate associated with this condition. Here we report a case of emphysematous osteomyelitis of the calcaneus in a sixty-one-year-old male with diabetes mellitus and end-stage renal disease.

Long-term persistence of viral RNA and inflammation in the CNS of macaques exposed to aerosolized Venezuelan equine encephalitis virus.

Venezuelan equine encephalitis virus (VEEV) is a positively-stranded RNA arbovirus of the genus Alphavirus that causes encephalitis in humans. Cynomolgus macaques are a relevant model of the human disease caused by VEEV and are useful in exploring pathogenic mechanisms and the host response to VEEV infection. Macaques were exposed to small-particle aerosols containing virus derived from an infectious clone of VEEV strain INH-9813, a subtype IC strain isolated from a human infection.

Reducing complications in reconstruction of the cervical esophagus with anterolateral thigh flap: The five points protocol.

Patients suffering from hypopharyngeal cancer commonly present in the advanced stage and undergo a circumferential pharyngolaryngectomy. The possibility to reconstruct the esophagus and achieve an oral alimentation can significantly reduce the additional burden of a jejunostomy. The cervical esophagus is usually reconstructed with jejunal free flap (JFF) or fasciocutaneous free flap such as the anterolateral thigh (ALT) free flap.