Assessment of shock index in healthy cats and in cats presenting to an emergency room with shock.

Objective: To prospectively compare the shock index (SI) in a population of healthy cats with a population of cats presenting to the emergency room (ER) deemed to be in a state of shock.

Design: Prospective cohort study of cats.

Setting: University teaching hospital.

Polygenic risk scores and embryonic screening: considerations for regulation.

Polygenic risk scores (PRSs) have recently been used to inform reproductive decision-making in the context of embryonic screening. While this is yet to be widespread, it is contested and raises several challenges. This article provides an overview of some of the ethical considerations that arise with using PRSs for embryo screening and offers a series of regulatory considerations for jurisdictions that may wish to permit this in the future.

A descriptive analysis of sarcopenia markers in young adults with down syndrome.

Background: Most body composition research in individuals with Down Syndrome (DS) has focused on overweight and obesity. Although limited research has shown muscle mass indexes and physical performance levels of adults with DS are similar to or lower than older adults with sarcopenia, there is still a large gap in the literature regarding sarcopenia.

Objective: This brief report provides a comprehensive descriptive analysis of sarcopenia and obesity markers in individuals with DS.

The Ethical Case for Decentralized Clinical Trials.

The recent pandemic spurred interest in innovative design for clinical trials. In particular, constraints on the public's ability to gather led to an increase in remote or decentralized clinical trials (DCTs). DCTs present an opportunity to extend the benefits of research to underserved populations, decrease burdens, increase access to trials, and fill knowledge gaps surrounding rare conditions, though they are not without their own unique challenges and risks.

The combination of infectious bronchitis virus BR1 and Mass vaccines provides broad protection.

Two vaccination-challenge trials were performed using a commercial infectious bronchitis virus (IBV) BR1 vaccine, given alone or combined with a commercial IBV Mass vaccine against challenges with IBV M41, 793B, D388 (QX), Q1, Brasil-1 or Variant 2 challenge viruses, which includes the IB viruses that are dominant in South America. The efficacy of the vaccines against the challenge viruses was investigated by determination of the ciliary activity of the tracheal epithelium after challenge. The level of protection induced by the IBV BR1 vaccine alone against the six IBV challenge strains, of which five were of heterologous genotypes, varied from 50% to 100% with an average of 80%.

Alopecia Areata Treatment Patterns and Satisfaction: Results of a Real-World Cross-Sectional Survey in Europe.

Introduction: Alopecia areata (AA) is an autoimmune disease that causes scalp, face, and/or body hair loss. Recently, oral treatments with kinases inhibition became the first approved therapies for severe AA. An understanding of the use and effectiveness of traditional therapies in real-world treatment settings is needed to guide integration of novel therapies into the treatment paradigm.

ADAMTS12 promotes fibrosis by restructuring extracellular matrix to enable activation of injury-responsive fibroblasts.

Fibrosis represents the uncontrolled replacement of parenchymal tissue with extracellular matrix (ECM) produced by myofibroblasts. While genetic fate-tracing and single-cell RNA-Seq technologies have helped elucidate fibroblast heterogeneity and ontogeny beyond fibroblast to myofibroblast differentiation, newly identified fibroblast populations remain ill defined, with respect to both the molecular cues driving their differentiation and their subsequent role in fibrosis. Using an unbiased approach, we identified the metalloprotease ADAMTS12 as a fibroblast-specific gene that is strongly upregulated during active fibrogenesis in humans and mice.

Transmembrane protein 53 craniotubular dysplasia (OMIM # 619727): The skeletal disease and consequent blindness of this new disorder.

Craniotubular dysplasia, Ikegawa type (OMIM #619727) denotes the autosomal recessive skeletal disease identified in 2021 featuring blindness acquired in childhood. Five young members of four Indian families harbored a homozygous indel within TMEM53 (OMIM *619722), the gene that encodes transmembrane protein 53 (TMEM53). When intact, TMEM53 spans the nuclear envelope of osteoprogenitor cells, dampens BMP-SMAD signaling, and thereby slows bone formation.

Impact of lung cancer screening on stage migration and mortality among the national Veterans Health Administration population with lung cancer.

Background: Despite randomized trials demonstrating a mortality benefit to low-dose computed tomography screening to detect lung cancer, uptake of lung cancer screening (LCS) has been slow, and the benefits of screening remain unclear in clinical practice.

Methods: This study aimed to assess the impact of screening among patients in the Veterans Health Administration (VA) health care system diagnosed with lung cancer between 2011 and 2018. Lung cancer stage at diagnosis, lung cancer-specific survival, and overall survival between patients with cancer who did and did not receive screening before diagnosis were evaluated.

TRIM71 mutations cause a neurodevelopmental syndrome featuring ventriculomegaly and hydrocephalus.

Congenital hydrocephalus, characterized by cerebral ventriculomegaly, is one of the most common reasons for paediatric brain surgery. Recent studies have implicated lin-41 (lineage variant 41)/TRIM71 (tripartite motif 71) as a candidate congenital hydrocephalus risk gene; however, TRIM71 variants have not been systematically examined in a large patient cohort or conclusively linked with an OMIM syndrome. Through cross-sectional analysis of the largest assembled cohort of patients with cerebral ventriculomegaly, including neurosurgically-treated congenital hydrocephalus (totalling 2697 parent-proband trios and 8091 total exomes), we identified 13 protein-altering de novo variants (DNVs) in TRIM71 in unrelated children exhibiting variable ventriculomegaly, congenital hydrocephalus, developmental delay, dysmorphic features and other structural brain defects, including corpus callosum dysgenesis and white matter hypoplasia.

Integration of rapid bioburden testing into production quality management systems and process control.

The move to integrated continuous bioprocessing (ICB), while providing a means for process intensification, can put added strain on process analytics when conventional methods are used. For instance, traditional microbial methods provide minimal value to ICB processes given that the time required for data to become available is much longer than a typical full cycle of the manufacturing process. Although rapid microbial detection has been in discussion for over 30 years, it is still not routinely deployed in commercial biopharmaceutical manufacturing.

AI and the need for justification (to the patient).

This paper argues that one problem that besets black-box AI is that it lacks algorithmic justifiability. We argue that the norm of shared decision making in medical care presupposes that treatment decisions ought to be justifiable to the patient. Medical decisions are justifiable to the patient only if they are compatible with the patient's values and preferences and the patient is able to see that this is so.

Process development and characterization for integrated continuous bioprocesses-Highlights from N-mAb.

The N-mAb case study was produced by the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) to support teaching and learning for both industry and to accelerate adoption of advanced manufacturing process technologies such as integrated continuous bioprocesses (ICB) for mAbs. Similar to the A-mAb case study, N-mAb presents the evolution of an integrated control strategy, from early clinical through process validation and commercial manufacturing with a focus on elements that are unique to integrated continuous bioprocesses. This publication presents a summary of the process design and characterization chapters to allow a greater focus on the unique elements relevant to that phase of development.

Primary results and characterization of patients with exceptional outcomes in a phase 1b study combining PARP and MEK inhibition, with or without anti-PD-L1, for BRCA wild-type, platinum-sensitive, recurrent ovarian cancer.

Background: This phase 1b study (ClinicalTrials.gov identifier NCT03695380) evaluated regimens combining PARP and MEK inhibition, with or without PD-L1 inhibition, for BRCA wild-type, platinum-sensitive, recurrent ovarian cancer (PSROC).

Methods: Patients with PSROC who had received one or two prior treatment lines were treated with 28-day cycles of cobimetinib 60 mg daily (days 1-21) plus niraparib 200 mg daily (days 1-28) with or without atezolizumab 840 mg (days 1 and 15).

A syndromic neurodevelopmental disorder caused by rare variants in PPFIA3.

PPFIA3 encodes the protein-tyrosine phosphatase, receptor-type, F-polypeptide-interacting-protein-alpha-3 (PPFIA3), which is a member of the LAR-protein-tyrosine phosphatase-interacting-protein (liprin) family involved in synapse formation and function, synaptic vesicle transport, and presynaptic active zone assembly. The protein structure and function are evolutionarily well conserved, but human diseases related to PPFIA3 dysfunction are not yet reported in OMIM. Here, we report 20 individuals with rare PPFIA3 variants (19 heterozygous and 1 compound heterozygous) presenting with developmental delay, intellectual disability, hypotonia, dysmorphisms, microcephaly or macrocephaly, autistic features, and epilepsy with reduced penetrance.

Changes in the quality of life in patients undergoing orthognathic therapy - A systematic review.

The aim of this study was to investigate the impact of orthognathic therapy on patients' quality of life. Therefore, a systematic review was conducted including all prospective studies that compared pretherapeutic and posttherapeutic Oral Health Impact Profile (OHIP) or Overall Quality of Life (OQOL) questionnaire scores. Studies in patients with congenital deformities, clefts, or posttraumatic or cancer-associated deformities were excluded.