Plateau and Patella: A Framework for Ipsilateral Injury Fixation.

Ipsilateral patella and tibial plateau fractures represent an extremely rare injury pattern. They are seldom discussed in literature, with no frameworks for management being reported that we were able to find. We report our experience and management of such an injury, suffered by a 57-year-old female patient with good premorbid functional status, by direct trauma to the right knee.

Personalized breast cancer onset prediction from lifestyle and health history information.

We propose a method to predict when a woman will develop breast cancer (BCa) from her lifestyle and health history features. To address this objective, we use data from the Alberta's Tomorrow Project of 18,288 women to train Individual Survival Distribution (ISD) models to predict an individual's Breast-Cancer-Onset (BCaO) probability curve. We show that our three-step approach-(1) filling missing data with multiple imputations by chained equations, followed by (2) feature selection with the multivariate Cox method, and finally, (3) using MTLR to learn an ISD model-produced the model with the smallest L1-Hinge loss among all calibrated models with comparable C-index.

Orthogonally induced differentiation of stem cells for the programmatic patterning of vascularized organoids and bioprinted tissues.

The generation of organoids and tissues with programmable cellular complexity, architecture and function would benefit from the simultaneous differentiation of human induced pluripotent stem cells (hiPSCs) into divergent cell types. Yet differentiation protocols for the overexpression of specific transcription factors typically produce a single cell type. Here we show that patterned organoids and bioprinted tissues with controlled composition and organization can be generated by simultaneously co-differentiating hiPSCs into distinct cell types via the forced overexpression of transcription factors, independently of culture-media composition.

A Comparative Analysis of Online Versus in-Person Opioid Overdose Awareness and Reversal Training for First-Year Medical Students.

Physicians trained in opioid use disorder (OUD) harm reduction can mitigate opioid overdose deaths by prescribing naloxone and educating patients about its use. Unfortunately, many physicians possess OUD stigma. Training during medical school presents an opportunity to reduce OUD stigma and improve opioid overdose reversal knowledge.

Skin substitutes with noncultured autologous skin cell suspension heal porcine full-thickness wounds in a one-stage procedure.

Clinical application of skin substitute is typically a two-stage procedure with application of skin substitute matrix to the wound followed by engraftment of a split-thickness skin graft (STSG). This two-stage procedure requires multiple interventions, increasing the time until the wound is epithelialised. In this study, the feasibility of a one-stage procedure by combining bioengineered collagen-chondroitin-6-sulfate (DS1) or decellularised fetal bovine skin substitute (DS2) with autologous skin cell suspension (ASCS) in a porcine full-thickness wound healing model was evaluated.

Biophysical Characterization of a Novel Tri-Layer Placental Allograft Membrane.

Placental tissues, including membranes composed of amnion and chorion, are promising options for the treatment of chronic wounds. Amnion and chorion contain multiple extracellular matrix (ECM) proteins and a multitude of growth factors and cytokines that, when used clinically, assist in the progression of difficult to heal wounds through restoration of a normal healing process. The objective of this study was to characterize the physical and biological properties of a dehydrated tri-layer placental allograft membrane (TPAM) consisting of a chorion layer sandwiched between two layers of amnion.

Geographical Differences in Cardiovascular Comorbidities and Outcomes of COVID-19 Hospitalized Patients in the USA.

Introduction: Cardiovascular comorbidities may predispose to adverse outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). However, across the USA, the burden of cardiovascular comorbidities varies significantly. Whether clinical outcomes of hospitalized patients with COVID-19 differ between regions has not yet been studied systematically.

Identification of proteins and cellular pathways targeted by 2-nitroimidazole hypoxic cytotoxins.

Tumour hypoxia negatively impacts therapy outcomes and continues to be a major unsolved clinical problem. Nitroimidazoles are hypoxia selective compounds that become entrapped in hypoxic cells by forming drug-protein adducts. They are widely used as hypoxia diagnostics and have also shown promise as hypoxia-directed therapeutics.

Massive posterior cranial vault erosion and its reconstruction: A peculiar presentation of "mega cisterna magna".

Dandy-Walker (DW) complex is a rare central nervous system malformation, commonly associated with complex non-neurological conditions, defined by four variants with characteristic anatomic features, still inadequately known for its etiological aspects. "Mega Cisterna Magna" (MCM) is a type of DW complex which is represented by an enlarged posterior cranial fossa. Though reduction cranioplasty has been reported in enlarged posterior cranial fossa malformations, however we report a peculiar case of MCM with massive posterior cranial bone erosion, presenting completely asymptomatic at an age of 8 years, without any associated co-morbidities till date, nor with any evident occipital mass at birth.

"Covidsubo": Stress-Induced Cardiomyopathy by Novel Coronavirus Disease 2019.

Introduction: COVID-19 is a rapidly growing infectious disease that represents an immediate threat for the health of millions of people around the world, both in direct and indirect ways.

Case Presentation: In the present report we describe the development of stress cardiomyopathy in a patient who was overwhelmingly stressed by watching the news coverage of the COVID-19 pandemic.

Conclusion: Physicians and scientists around the globe should be aware of the psychological consequences of COVID-19 and their potential to cause physical illness.

BIK drives an aggressive breast cancer phenotype through sublethal apoptosis and predicts poor prognosis of ER-positive breast cancer.

Apoptosis is fundamental to normal animal development and is the target for many anticancer therapies. Recent studies have explored the consequences of "failed apoptosis" where the apoptotic program is initiated but does not go to completion and does not cause cell death. Nevertheless, this failed apoptosis induces DNA double-strand breaks generating mutations that facilitate tumorigenesis.

Biological characterization of dehydrated amniotic membrane allograft: Mechanisms of action and implications for wound care.

There is a growing clinical demand in the wound care market to treat chronic wounds such as diabetic foot ulcers. Advanced cell and tissue-based products (CTPs) are often used to address challenging chronic wounds where healing has stalled. These products contain active biologics such as growth factors and cytokines as well as structural components that support and stimulate cell growth and assist in tissue regeneration.

Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels.

Engineering organ-specific tissues for therapeutic applications is a grand challenge, requiring the fabrication and maintenance of densely cellular constructs composed of ~10 cells/ml. Organ building blocks (OBBs) composed of patient-specific-induced pluripotent stem cell-derived organoids offer a pathway to achieving tissues with the requisite cellular density, microarchitecture, and function. However, to date, scant attention has been devoted to their assembly into 3D tissue constructs.

Clinical and biological characterization of skeletal muscle tissue biopsies of surgical cancer patients.

Background: Researchers increasingly use intraoperative muscle biopsy to investigate mechanisms of skeletal muscle atrophy in patients with cancer. Muscles have been assessed for morphological, cellular, and biochemical features. The aim of this study was to conduct a state-of-the-science review of this literature and, secondly, to evaluate clinical and biological variation in biopsies of rectus abdominis (RA) muscle from a cohort of patients with malignancies.

Fine-mapping of a novel premenopausal breast cancer susceptibility locus at Chr4q31.22 in Caucasian women and validation in African and Chinese women.

We previously identified a novel breast cancer susceptibility variant on chromosome 4q31.22 locus (rs1429142) conferring risk among women of European ancestry. Here, we report replication of findings, validation of the variant in diverse populations and fine-mapping of the associated locus in Caucasian population.

Oncogenic activity of poly (ADP-ribose) glycohydrolase.

Poly (ADP-ribosylation), known as PARylation, is a post-translational modification catalyzed by poly (ADP-ribose) polymerases (PARP) and primarily removed by the enzyme poly (ADP-ribose) glycohydrolase (PARG). While the aberrant removal of post-translation modifications including phosphorylation and methylation has known tumorigenic effects, deregulation of PARylation has not been widely studied. Increased hydrolysis of PARylation chains facilitates cancer growth through enhancing estrogen receptor (ER)-driven proliferation, but oncogenic transformation has not been linked to increased PARG expression.

Single-Nucleotide Polymorphisms in TAOK3 Are Associated With High Opioid Requirement for Pain Management in Patients With Advanced Cancer Admitted to a Tertiary Palliative Care Unit.

Purpose: Different amounts of opioid are required for the relief of cancer pain in different individuals, raising the possibility that genetic factors play a role. We tested the hypothesis that genetic variations in the TAOK3 (TAO kinase 3, encoding serine/threonine-protein kinase) explain some of the interindividual variations related to the morphine-equivalent daily dose (MEDD) in patients with cancer.

Experimental Design: We selected two single-nucleotide polymorphisms (SNPs) in the TAOK3, reported earlier to associate with higher MEDD in postoperative pain based on genome-wide association study.

The Challenges and Opportunities in the Clinical Application of Noncoding RNAs: The Road Map for miRNAs and piRNAs in Cancer Diagnostics and Prognostics.

Discoveries on nonprotein-coding RNAs have induced a paradigm shift in our overall understanding of gene expression and regulation. We now understand that coding and noncoding RNA machinery work in concert to maintain overall homeostasis. Based on their length, noncoding RNAs are broadly classified into two groups-long (>200 nt) and small noncoding RNAs (<200 nt).

Breast cancer associated germline structural variants harboring small noncoding RNAs impact post-transcriptional gene regulation.

Copy Number Variants (CNVs) are a class of structural variations of DNA. Germline CNVs are known to confer disease susceptibility, but their role in breast cancer warrants further investigations. We hypothesized that breast cancer associated germline CNVs contribute to disease risk through gene dosage or other post-transcriptional regulatory mechanisms, possibly through tissue specific expression of CNV-embedded small-noncoding RNAs (CNV-sncRNAs).

Sarcopenia and myosteatosis are accompanied by distinct biological profiles in patients with pancreatic and periampullary adenocarcinomas.

Introduction: Pancreatic and periampullary adenocarcinomas are associated with abnormal body composition visible on CT scans, including low muscle mass (sarcopenia) and low muscle radiodensity due to fat infiltration in muscle (myosteatosis). The biological and clinical correlates to these features are poorly understood.

Methods: Clinical characteristics and outcomes were studied in 123 patients who underwent pancreaticoduodenectomy for pancreatic or non-pancreatic periampullary adenocarcinoma and who had available preoperative CT scans.

Taxane acute pain syndrome (TAPS) in patients receiving chemotherapy for breast or prostate cancer: a prospective multi-center study.

Background: Taxane acute pain syndrome (TAPS) is characterized by myalgias and arthralgias starting 2-3 days after taxane-based chemotherapy and lasting up to 7 days. In the absence of validated tools, many studies use the presence of both the myalgia and arthralgia components of the Common Terminology Criteria for Adverse Events (CTCAE) to define TAPS. The present study prospectively evaluated the frequency, severity, and impact of TAPS in patients with breast or prostate cancer.

Cardiac sarcoidosis presenting as arrhythmogenic right ventricular cardiomyopathy/dysplasia with ventricular aneurysms: a case report.

A 70-year old Caucasian man with recurrent ventricular tachycardia and progressive biventricular failure attributed to arrhythmogenic right ventricular cardiomyopathy/dysplasia was evaluated for heart transplantation. Cardiac ventriculography revealed an abnormal left ventricle with five saccular aneurysms. Heart transplantation was performed.

Determination of the Relative Efficacy of Eicosapentaenoic Acid and Docosahexaenoic Acid for Anti-Cancer Effects in Human Breast Cancer Models.

Epidemiological studies have associated high fish oil consumption with decreased risk of breast cancer (BC). n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish and fish oils exert anti-cancer effects. However, few studies have examined the relative efficacy of EPA and DHA alone and in mixtures on BC subtypes.