PARP Inhibition Sensitizes Breast Cancer Cells to Eribulin.

Background: Poly(ADP-ribose) polymerases 1 and 2 (PARP1, 2), and 3 mediate protein modifications that facilitate the recruitment of DNA repair factors to single and double strand breaks. PARP3 is unique in that it is also required for efficient mitotic progression and stabilization of the mitotic spindle. Eribulin, an anti-microtubule agent used clinically to treat breast cancer, exerts its cytotoxicity by altering microtubule dynamics resulting in cell cycle arrest and apoptosis.

Results from a living systematic review of the prevalence of mood and anxiety disorders and factors associated with symptoms in systemic sclerosis.

We aimed to synthesize evidence on (1) the prevalence of mood and anxiety disorders and (2) factors associated with symptoms in systemic sclerosis (SSc). We searched MEDLINE, CINAHL, EMBASE, Cochrane CENTRAL, and PsycINFO via an ongoing living systematic review with automated monthly searches. We identified 6 eligible studies through March 1, 2023.

Examining an Altruism-Eliciting Video Intervention to Increase COVID-19 Vaccine Intentions in Younger Adults: A Qualitative Assessment Using the Realistic Evaluation Framework.

COVID-19 vaccine-induced immunity wanes over time, and with the emergence of new variants, additional "booster" doses have been recommended in Canada. However, booster vaccination uptake has remained low, particularly amongst younger adults aged 18-39. A previous study by our research team found that an altruism-eliciting video increased COVID-19 vaccination intentions.

Patient-Reported Outcome Measures of Psychosocial Quality of Life in Oropharyngeal Cancer Patients: A Scoping Review.

Oropharyngeal squamous cell carcinoma (OPSCC) patients are burdened by the effect of the disease process and treatment toxicities on organs important in everyday activities, such as breathing, speaking, eating, and drinking. There is a rise in OPSCC due to human papilloma virus (HPV)-associated OPSCC, affecting younger and healthier patients and with a better overall prognosis. Emphasis must be shared between oncologic outcomes and the effects on quality of life.

Cardiac mRNA Is Predominantly Expressed in the Right Atrium and Does Not Respond to Iron.

Hepcidin is a liver-derived hormone that controls systemic iron traffic. It is also expressed in the heart, where it acts locally. We utilized cell and mouse models to study the regulation, expression, and function of cardiac hepcidin.

Single substitution in H3.3G34 alters DNMT3A recruitment to cause progressive neurodegeneration.

Germline histone H3.3 amino acid substitutions, including H3.3G34R/V, cause severe neurodevelopmental syndromes.

DDX47 untangles R-loops with only certain other helicases.

R-loops, formed transiently during gene transcription, are tightly controlled to avoid conflict with ongoing processes. Marchena-Cruz et al. identified DExD/H box RNA helicase DDX47 using a new R-loop resolving screen and defined a unique role for this helicase in nucleolar R-loops and its interplay with senataxin (SETX) and DDX39B.

Discovery-Based Proteomics Identify Skeletal Muscle Mitochondrial Alterations as an Early Metabolic Defect in a Mouse Model of β-Thalassemia.

Although metabolic complications are common in thalassemia patients, there is still an unmet need to better understand underlying mechanisms. We used unbiased global proteomics to reveal molecular differences between the th mouse model of thalassemia and wild-type control animals focusing on skeletal muscles at 8 weeks of age. Our data point toward a significantly impaired mitochondrial oxidative phosphorylation.

Characteristics of Mutation in Thyroid Tumours: A Retrospective Chart Review.

While some studies suggest that mutations correlate with a low-risk phenotype in pediatric thyroid nodules, the relationship between the mutation and malignancy in the adult populations is abstruse. This study investigated whether mutations result in thyroid malignancy, and whether these malignancies are aggressive. This multicenter study involved 316 patients who underwent preoperative molecular testing, and subsequent lobectomy or total thyroidectomy at two quaternary care hospitals.

Humoral Responses against BQ.1.1 Elicited after Breakthrough Infection and SARS-CoV-2 mRNA Vaccination.

The Omicron BQ.1.1 variant is now the major SARS-CoV-2 circulating strain in many countries.

Differences in Disability Perception in Systemic Sclerosis: A Mirror Survey of Patients and Health Care Providers.

Differences in disability perception between patients and care providers may impact outcomes. We aimed to explore differences in disability perception between patients and care providers in systemic sclerosis (SSc). We conducted a cross-sectional internet-based mirror survey.

Molecular Genetic Characteristics of , a Proposed New Ovarian Cancer Predisposing Gene.

was recently identified as a new candidate ovarian cancer (OC)-predisposing gene from the genetic analysis of carriers of c.1813C>T; p.L605F in OC families.

Primary Cutaneous Multifocal Indolent CD8+ T-Cell Lymphoma: A Novel Primary Cutaneous CD8+ T-Cell Lymphoma.

We report the case of a patient who was referred to our institution with a diagnosis of CD4+ small/medium-sized pleomorphic lymphoma. At the time, the patient showed a plethora of lesions mainly localizing to the legs; thus, we undertook studies to investigate the lineage and immunophenotype of the neoplastic clone. Immunohistochemistry (IHC) showed marked CD4 and CD8 positivity.

Oncologic Outcomes of Surgically Treated Cervical Cancer with No Residual Disease on Hysterectomy Specimen: A 4C (Canadian Cervical Cancer Collaborative) Working Group Study.

Minimally invasive surgery for the treatment of macroscopic cervical cancer leads to worse oncologic outcomes than with open surgery. Preoperative conization may mitigate the risk of surgical approach. Our objective was to describe the oncologic outcomes in cases of cervical cancer initially treated with conization, and subsequently found to have no residual cervical cancer after hysterectomy performed via open and minimally invasive approaches.

Efficacy and Safety of Sonic Hedgehog Inhibitors in Basal Cell Carcinomas: An Updated Systematic Review and Meta-analysis (2009-2022).

Background: Basal cell carcinoma (BCC) of the skin is the most common form of skin cancer in the United States. In life-threatening, advanced BCC, sonic hedgehog inhibitors (SSHis) remain a pre-eminent treatment option for locally advanced BCC and metastatic BCC.

Objective: In this updated systematic review and meta-analysis, we aimed to better characterize the efficacy and safety of SSHis by including final updates from pivotal clinical trials and additional new recent studies.

Applying the column generation method to the intensity modulated high dose rate brachytherapy inverse planning problem.

Intensity modulated high dose rate brachytherapy (IMBT) is a rapidly developing application of brachytherapy where anisotropic dose distributions can be produced at each source dwell position. This technique is made possible by placing rotating metallic shields inside brachytherapy needles or catheters. By dynamically directing the radiation towards the tumours and away from the healthy tissues, a more conformal dose distribution can be obtained.

Phosphorus Overload Promotes Hepatic Lipolysis by Suppressing GSK3β-Dependent Phosphorylation of PPARα at Ser84 and Thr265 in a Freshwater Teleost.

Excessive phosphorus (Pi) contributes to eutrophication in an aquatic environment, which threatens human and fish health. However, the mechanisms by which Pi overload influences aquatic animals remain largely unexplored. In the present study, Pi supplementation increased the Pi content, inhibited lipid accumulation and lipogenesis, and stimulated lipolysis in the liver.

Structural basis of mammalian respiratory complex I inhibition by medicinal biguanides.

The molecular mode of action of biguanides, including the drug metformin, which is widely used in the treatment of diabetes, is incompletely characterized. Here, we define the inhibitory drug-target interaction(s) of a model biguanide with mammalian respiratory complex I by combining cryo-electron microscopy and enzyme kinetics. We interpret these data to explain the selectivity of biguanide binding to different enzyme states.

Genetic Iron Overload Hampers Development of Cutaneous Leishmaniasis in Mice.

The survival, growth, and virulence of spp., a group of protozoan parasites, depends on the proper access and regulation of iron. Macrophages, host cell, may divert iron traffic by reducing uptake or by increasing the efflux of iron via the exporter ferroportin.

Effect of Having Concurrent Mutations on the Degree of Aggressiveness in Patients with Thyroid Cancer Positive for Promoter Mutations.

This study aimed to examine whether concurrent mutations with a promoter mutation are associated with a greater likelihood of more aggressive disease than a promoter mutation alone. The medical records of 1477 patients who underwent thyroid surgery at two tertiary hospitals between 2017 and 2022 were reviewed. Twenty-four patients had promoter mutations based on molecular profile testing.

Etiological Roles of p75 in a Mouse Model of Wet Age-Related Macular Degeneration.

Choroidal neovascularization (CNV) is a pathological angiogenesis of the choroidal plexus of the retina and is a key feature in the wet form of age-related macular degeneration. Mononuclear phagocytic cells (MPCs) are known to accumulate in the subretinal space, generating a chronic inflammatory state that promotes the growth of the choroidal neovasculature. However, how the MPCs are recruited and activated to promote CNV pathology is not fully understood.