HMGA1 induces FGF19 to drive pancreatic carcinogenesis and stroma formation.

High mobility group A1 (HMGA1) chromatin regulators are upregulated in diverse tumors where they portend adverse outcomes, although how they function in cancer remains unclear. Pancreatic ductal adenocarcinomas (PDACs) are highly lethal tumors characterized by dense desmoplastic stroma composed predominantly of cancer-associated fibroblasts and fibrotic tissue. Here, we uncover an epigenetic program whereby HMGA1 upregulates FGF19 during tumor progression and stroma formation.

Trunk Biomechanics in Individuals with Knee Disorders: A Systematic Review with Evidence Gap Map and Meta-analysis.

Background: The trunk is the foundation for transfer and dissipation of forces throughout the lower extremity kinetic chain. Individuals with knee disorders may employ trunk biomechanical adaptations to accommodate forces at the knee or compensate for muscle weakness. This systematic review aimed to synthesize the literature comparing trunk biomechanics between individuals with knee disorders and injury-free controls.

Beginning With the End in Mind: Implementing Backward Design to Improve Sports Injury Rehabilitation Practices.

Current injury-specific return-to-performance rehabilitation programs are not comprehensive, lack intensity, and need better tailoring to the demands of sport. The vast number of rehabilitation and return to sport protocols also reflects a lack of consensus about what the best program looks like, which hinders beginning practitioners from implementing best practices across the spectrum of injuries and sports. Backward design, which has underpinnings in educational research, can facilitate implementation by encouraging practitioners to begin with the end in mind before logically and intentionally working backwards to design transferable and context-specific rehabilitation plans that improve sports injury rehabilitation practices.

Do Cutting Kinematics Change as Boys Mature? A Longitudinal Cohort Study of High-School Athletes.

Objective: Examine longitudinal changes in trunk, hip, and knee kinematics in maturing boys during an unanticipated cutting task.

Design: Prospective cohort study.

Setting: Biomechanical laboratory.

Non-contact Anterior Cruciate Ligament Injury Epidemiology in Team-Ball Sports: A Systematic Review with Meta-analysis by Sex, Age, Sport, Participation Level, and Exposure Type.

Background: Not all anterior cruciate ligament (ACL) injuries are preventable. While some ACL injuries are unavoidable such as those resulting from a tackle, others that occur in non-contact situations like twisting and turning in the absence of external contact might be more preventable. Because ACL injuries commonly occur in team ball-sports that involve jumping, landing and cutting manoeuvres, accurate information about the epidemiology of non-contact ACL injuries in these sports is needed to quantify their extent and burden to guide resource allocation for risk-reduction efforts.

Mastering the Topic, the Message, and the Delivery: Leveraging the Social Marketing Mix to Better Implement Sports Injury Prevention Programs.

Social marketing is successful at tackling global health threats and social change but has not been fully explored in sports injury prevention contexts. The social marketing mix (product, price, place, and promotion) can help create exercise-based injury prevention programs with high-value propositions that will be relevant to their implementation (adoption, adherence, maintenance). To improve the real-world effectiveness of injury prevention programs, we share steps that researchers and sports administrators can take tomorrow to leverage the social marketing mix to encourage downstream consumers, such as coaches, clinicians, parents, and athletes, to implement injury prevention programs.

Evaluating the validity and reliability of inertial measurement units for determining knee and trunk kinematics during athletic landing and cutting movements.

Inertial Measurement Units (IMUs) are promising alternatives to laboratory-based motion capture methods in biomechanical assessment of athletic movements. The aim of this study was to investigate the validity of an IMU system for determining knee and trunk kinematics during landing and cutting tasks for clinical and research applications in sporting populations. Twenty-seven participants performed five cutting and landing tasks while being recorded using a gold-standard optoelectronic motion capture system and an IMU system.

When puberty strikes: Longitudinal changes in cutting kinematics in 172 high-school female athletes.

Objectives: Young female athletes involved in high-speed cutting and change-of-direction sports are particularly susceptible to anterior cruciate ligament (ACL) injuries. Little is known if maturational changes in cutting technique contribute to the increased injury risk. Our objective was to examine longitudinal changes in cutting kinematics in female athletes as they matured through puberty.

Trunk endurance, posterior chain flexibility, and previous history of musculoskeletal pain predict overuse low back and lower extremity injury: a prospective cohort study of 545 Navy Cadets.

Objective: To investigate predictors of low back and lower extremity musculoskeletal injury in a cohort of Naval cadets.

Design: Prospective Cohort Study METHODS: 545 Naval cadets (Males, n = 394, 72%) were followed-up over eight months. Nine variables were investigated as predictors: history of musculoskeletal symptoms in the last 12 months, ankle dorsiflexion range of motion, sit and reach test, isometric hip abduction and external rotation strength, alignment during the single leg squat test, single leg hop test for distance, prone plank and side plank tests.

Limited Support for Trunk and Hip Deficits as Risk Factors for Athletic Knee Injuries: A Systematic Review With Meta-analysis and Best-Evidence Synthesis.

Objective: To determine whether neuromuscular deficits in trunk and hip-related function are risk factors for athletic knee injuries.

Design: Etiology systematic review with meta-analysis.

Literature Search: Six online databases (MEDLINE, Web of Science, Embase, CINAHL, Scopus, and SPORTDiscus) were searched up to April 2019.

Functional Loss of and Activates Alternative Lengthening of Telomeres (ALT) in LAPC4 Prostate Cancer Cells.

A key hallmark of cancer, unlimited replication, requires cancer cells to evade both replicative senescence and potentially lethal chromosomal instability induced by telomere dysfunction. The majority of cancers overcome these critical barriers by upregulating telomerase, a telomere-specific reverse transcriptase. However, a subset of cancers maintains telomere lengths by the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway.

High mobility group A1 (HMGA1) protein and gene expression correlate with ER-negativity and poor outcomes in breast cancer.

Purpose: The high mobility group A1 (HMGA1) chromatin remodeling protein is required for metastatic progression and cancer stem cell properties in preclinical breast cancer models, although its role in breast carcinogenesis has remained unclear. To investigate HMGA1 in primary breast cancer, we evaluated immunoreactivity score (IRS) in tumors from a large cohort of Asian women; HMGA1 gene expression was queried from two independent Western cohorts.

Methods: HMGA1 IRS was generated from breast tumors in Korean women as the product of staining intensity (weak = 1, moderate = 2, strong = 3) and percent positive cells (< 5% = 0, 5-30% = 1, 30-60% = 2, > 60% = 3), and stratified into three groups: low (< 3), intermediate (3-6), high (> 6).

Genetic Engineering of Primary Mouse Intestinal Organoids Using Magnetic Nanoparticle Transduction Viral Vectors for Frozen Sectioning.

Intestinal organoid cultures provide a unique opportunity to investigate intestinal stem cell and crypt biology in vitro, although efficient approaches to manipulate gene expression in organoids have made limited progress in this arena. While CRISPR/Cas9 technology allows for precise genome editing of cells for organoid generation, this strategy requires extensive selection and screening by sequence analysis, which is both time-consuming and costly. Here, we provide a detailed protocol for efficient viral transduction of intestinal organoids.

Lessons from the Crypt: HMGA1-Amping up Wnt for Stem Cells and Tumor Progression.

High mobility group A1 (HMGA1) chromatin remodeling proteins are enriched in aggressive cancers and stem cells, although their common function in these settings has remained elusive until now. Recent work in murine intestinal stem cells (ISC) revealed a novel role for Hmga1 in enhancing self-renewal by amplifying Wnt signaling, both by inducing genes expressing Wnt agonist receptors and Wnt effectors. Surprisingly, Hmga1 also "builds" a stem cell niche by upregulating , a factor required for differentiation to Paneth cells; these cells constitute an epithelial niche by secreting Wnt and other factors to support ISCs.