A Novel Homozygous Mutation Causes Ovarian Dysgenesis and Primary Amenorrhea.

Context: Despite a growing number of studies, the genetic etiology in many cases of ovarian dysgenesis is incompletely understood.

Objectives: This work aimed to study the genetic etiology causing absence of spontaneous pubertal development, hypergonadotropic hypogonadism, and primary amenorrhea in 2 sisters.

Methods: Whole-exome sequencing was performed on DNA extracted from peripheral lymphocytes of 2 Palestinian sisters born to consanguineous parents.

Real-world trends and future projections of the prevalence of cirrhosis and hepatic encephalopathy among commercially and Medicare-insured adults in the United States.

Objectives: Describing cirrhosis and hepatic encephalopathy (HE) burden over time can inform clinical management and resource allocation. Using health care claims data, this observational study examined recent trends in the prevalence of cirrhosis and HE and associated health care resource utilization among commercially and Medicare-insured adults in the United States (US).

Methods: Data from the MarketScan Commercial Claims and Encounters Database and 100% Medicare Research Identifiable Files were analyzed (2007-2020).

A phase I clinical trial of intrahepatic artery delivery of TG6002 in combination with oral 5-fluorocytosine in patients with liver-dominant metastatic colorectal cancer.

Background: Effective treatment for patients with metastatic cancer is limited, particularly for colorectal cancer patients with metastatic liver lesions (mCRC), where accessibility to numerous tumours is essential for favourable clinical outcomes. Oncolytic viruses (OVs) selectively replicate in cancer cells; however, direct targeting of inaccessible lesions is limited when using conventional intravenous or intratumoural administration routes.

Methods: We conducted a multi-centre, dose-escalation, phase I study of vaccinia virus, TG6002, via intrahepatic artery (IHA) delivery in combination with the oral pro-drug 5-fluorocytosine to fifteen mCRC patients.

Challenges and motivating factors for integrating geostatistical models in targeted schistosomiasis control: A qualitative case study in Northwestern Tanzania.

Introduction: To address problems of over- and under-treatment with preventive chemotherapy resulting in ongoing transmission of schistosomiasis, the World Health Organization (WHO) recommends targeted mass drug administration (MDA) interventions at a sub-district level. In Tanzania, the lack of sub-district (ward) prevalence data has inhibited a transition to targeted treatment. Model-based prevalence estimation combined with routine surveillance data can be used to overcome this gap.

A non-systematic overview review of self-focused emotion regulation in autistic individuals through the lens of the extended process model.

We know that many autistic children, youth, and adults experience difficulties regulating emotions. Existing research has focused mainly on the differences in emotion regulation capabilities between autistic and non-autistic individuals, the relationships between autistic traits and emotion regulation, and how emotion regulation relates to other outcomes, such as social skills and mental health.We want to take a new approach to review the existing emotion regulation research through the lens of a specific theoretical model: the extended process model of emotion regulation.

Protein shapeshifting in necroptotic cell death signaling.

Necroptosis is a mode of programmed cell death executed by the mixed lineage kinase domain-like (MLKL) pseudokinase following its activation by the upstream receptor-interacting protein kinase-3 (RIPK3), subsequent to activation of death, Toll-like, and pathogen receptors. The pathway originates in innate immunity, although interest has surged in therapeutically targeting necroptosis owing to its dysregulation in inflammatory diseases. Here, we explore how protein conformation and higher order assembly of the pathway effectors - Z-DNA-binding protein-1 (ZBP1), RIPK1, RIPK3, and MLKL - can be modulated by post-translational modifications, such as phosphorylation, ubiquitylation, and lipidation, and intermolecular interactions to tune activities and modulate necroptotic signaling flux.

"It's Just Good Science": A Qualitative Study Exploring Equity, Diversity, and Inclusion in Canadian Arthritis Research.

Objective: Despite knowledge that health outcomes vary according to patient characteristics, identity, and geography, including underrepresented populations in arthritis research remains a challenge. We conducted interviews to explore how researchers in arthritis have used equity, diversity, and inclusion (EDI) principles to inform their research.

Methods: Semistructured interviews were conducted with individuals who 1) have experience conducting arthritis research studies, 2) reside in and/or conduct their research in Canada, and 3) speak English or French.

Real-time optical fibre near-infrared chromatic dispersion analyser using collocated optical fibre gratings.

We present what we believe to be a novel optical fibre device for real-time measurements of near-infrared chromatic dispersion of a liquid medium from 1100 nm to 1700 nm. This inline optical fibre chromatic dispersion analyser is based upon collocated fibre long-period gratings written adjacently in the core by femtosecond laser inscription yielding 8 attenuation bands associated with different cladding modes, yielding 8 independent measurements. This fibre device is tested on a series of chemical compounds associated with wines.

MLKL deficiency elevates testosterone production in male mice independently of necroptotic functions.

Mixed lineage kinase domain-like (MLKL) is a pseudokinase, best known for its role as the terminal effector of the necroptotic cell death pathway. MLKL-mediated necroptosis has long been linked to various age-related pathologies including neurodegeneration, atherosclerosis and male reproductive decline, however many of these attributions remain controversial. Here, we investigated the role of MLKL and necroptosis in the adult mouse testis: an organ divided into sperm-producing seminiferous tubules and the surrounding testosterone-producing interstitium.

Divergent roles of RIPK3 and MLKL in high-fat diet-induced obesity and MAFLD in mice.

Cell death frequently occurs in the pathogenesis of obesity and metabolic dysfunction-associated fatty liver disease (MAFLD). However, the exact contribution of core cell death machinery to disease manifestations remains ill-defined. Here, we show via the direct comparison of mice genetically deficient in the essential necroptotic regulators, receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like (MLKL), as well as mice lacking apoptotic caspase-8 in myeloid cells combined with RIPK3 loss, that RIPK3/caspase-8 signaling regulates macrophage inflammatory responses and drives adipose tissue inflammation and MAFLD upon high-fat diet feeding.

Early insights from the routine use of patient reported outcome measures in elective hip and knee arthroplasty at a public teaching hospital in South Australia.

Introduction: For advanced osteoarthritis of the knee and hip, the most clinically effective treatment remains total-knee arthroplasty (TKA) and total-hip arthroplasty (THA). Success of these surgeries have traditionally been appraised by economic and volume-based measures. There has been a shift towards the use of patient reported outcome measures (PROMs) to quantify success and guide treatment.

In situ visualization of endothelial cell-derived extracellular vesicle formation in steady state and malignant conditions.

Endothelial cells are integral components of all vasculature within complex organisms. As they line the blood vessel wall, endothelial cells are constantly exposed to a variety of molecular factors and shear force that can induce cellular damage and stress. However, how endothelial cells are removed or eliminate unwanted cellular contents, remains unclear.

Assessment of the Effectiveness of Desensitizing Dentifrices on Management of Dental Hypersensitivity: An Study.

Aim: The current study aimed to assess the efficiency of two desensitizing dentifrices on the management of dental hypersensitivity.

Materials And Methods: For the purpose of this investigation, 60 extracted human sound premolar teeth that were removed for orthodontic purposes were collected. On the buccal cervical areas, an inverted-cone bur was used to create cavities that were 2 mm deep and 3 mm wide.

Benefits, barriers and recommendations for youth engagement in health research: combining evidence-based and youth perspectives.

Background: Youth engagement refers to the collaboration between researchers and youth to produce research. Youth engagement in health research has been shown to inform effective interventions aimed at improving health outcomes. However, limited evidence has identified promising practices to meaningfully engage youth.

Examining the Link Between Social Affect and Visual Exploration of Cute Stimuli in Autistic Children.

Baby schema refers to physical features perceived as cute, known to trigger attention, induce positive emotions, and prompt social interactions. Given the reduced visual attention to social stimuli observed in individuals on the autism spectrum, the current study examines whether the sensitivity to baby schema is also affected. We expected that the looking time towards cute-featured stimuli would vary with symptom severity levels and would be associated with social affect.

The first BILGENSA Research Network workshop in Zambia: identifying research priorities, challenges and needs in genital bilharzia in Southern Africa.

Female genital schistosomiasis (FGS) and male genital schistosomiasis (MGS) are gender-specific manifestations of urogenital schistosomiasis. Morbidity is a consequence of prolonged inflammation in the human genital tract caused by the entrapped eggs of the waterborne parasite, Both diseases affect the sexual and reproductive health (SRH) of millions of people globally, especially in sub-Sahara Africa (SSA). Awareness and knowledge of these diseases is largely absent among affected communities and healthcare workers in endemic countries.

"If I chose to listen to people, I possibly wouldn't be using family planning": Impact of external influences on women's contraceptive autonomy in rural Northwest Tanzania.

Background: There is an increasing emphasis on promoting women's autonomy in reproductive decision-making, particularly given global efforts to increase contraceptive access and uptake. Scales to quantify autonomy have inconsistently included the effect of external influences and focused primarily on influences of partners.

Objectives: This study aimed to gain greater depth in understanding how influences including and beyond a woman's partner affect her contraceptive decision-making, as well as how external influences can overlap and further complicate contraceptive decision-making.

Mapping where and when necroptotic cell death occurs in disease.

A series of recent studies have established where the necroptosis machinery — RIPK1, RIPK3, MLKL, ZBP1 and Caspase-8 — occur and are activated in mouse and human tissues, and how ZBP1 splicing might regulate necroptosis. These studies highlight the importance of mapping necroptosis spatially to understand how pathway dysregulation can lead to disease.

E7-mediated repression of miR-203 promotes LASP1-dependent proliferation in HPV-positive cervical cancer.

Human papillomaviruses (HPV) are a major cause of malignancy, contributing to ~5% of all human cancers worldwide, including most cervical cancer cases and a growing number of anogenital and oral cancers. The major HPV viral oncogenes, E6 and E7, manipulate many host cellular pathways that promote cell proliferation and survival, predisposing infected cells to malignant transformation. Despite the availability of highly effective vaccines, there are still no specific anti-viral therapies targeting HPV or treatments for HPV-associated cancers.

An immunohistochemical atlas of necroptotic pathway expression.

Necroptosis is a lytic form of regulated cell death reported to contribute to inflammatory diseases of the gut, skin and lung, as well as ischemic-reperfusion injuries of the kidney, heart and brain. However, precise identification of the cells and tissues that undergo necroptotic cell death in vivo has proven challenging in the absence of robust protocols for immunohistochemical detection. Here, we provide automated immunohistochemistry protocols to detect core necroptosis regulators - Caspase-8, RIPK1, RIPK3 and MLKL - in formalin-fixed mouse and human tissues.

Barriers and facilitators to implementing a Canadian shared-care ADHD program in pediatric settings in Shanghai: a consolidated framework for implementation research approach.

Objectives: The vast majority of children with Attention-Deficit Hyperactivity Disorder (ADHD) do not have access to proper diagnosis and treatment in China. The goal of this project is to identify the challenges and facilitators in implementing a Canadian ADHD Shared Care Pathways program in pediatric settings in Shanghai region.

Methods: Purposive semi-structured focus groups were conducted on a total of 13 healthcare practitioners from the Shanghai Xinuha, Ninghai and Chongming hospitals.

Evaluation of Stages, Treatment Protocols, and Outcomes of Colorectal Cancer among West Bank Patients.

Colorectal cancer (CRC) is the second most widespread cancer among Palestinian patients. As cancer care improves in hospitals across the West Bank, services like palliative care, targeted therapy, bone marrow transplantation, and individualized therapy are still limited. This study aimed to assess the CRC stages, treatment protocols, and survival rates of patients in the West Bank.