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g. anti-mitotic agents). We also revealed reduced activity of MCL-1 inhibitors in the presence of stromal support as a drug-class effect which was overcome by concurrent Bcl-xL or Bcl-2 inhibition. Finally, we demonstrate heterogeneous Bcl-2 family deregulation and MCL-1 inhibitor cross-resistance in carfilzomib resistant cells, a phenomenon linked to MDR1-driven drug efflux of MCL-1 inhibitors. The implications of our findings for clinical practice underline the need for patient adapted treatment protocols, with the tracking of tumour and/or clone specific adaptations in response to MCL-1 inhibition.
High school (HS) and youth sports organizations (YSO) that restarted participation in the fall of 2020 during the COVID-19 pandemic relied on information sources to develop risk mitigation procedures.

To compare the risk mitigation procedures being employed and the information sources being utilized by HS athletic departments and YSO.

Surveys were distributed to HS athletic directors and youth sports directors throughout the US regarding sport restarting, COVID-19 cases, risk reduction procedures, and the information sources used to develop risk reduction plans in fall 2020. The proportion of HS and YSO using different procedures and information sources were compared using chi-square tests.

HS and YSO programs from across the US Participants 1296 HS and 584 YSO responded, representing 519,241 adolescent athletes.

Risk reduction procedures used and information sources employed Results HS employed more risk reduction procedures (7.1±2.1 v 6.3±2.4, p<0.001), were more likely to use symptom monitorinrt using a broad range of risk reduction procedures, but the average number was higher among high schools than youth sports organizations. Use of information from the CDC and local health authorities was high overall, but low from professional healthcare organizations. Epacadostat molecular weight Professional healthcare organizations should consider additional measures to improve information uptake among stakeholders within youth sports.Liver development is controlled by key signals and transcription factors that drive cell proliferation, migration, differentiation and functional maturation. In the adult liver, cell maturity can be perturbed by genetic and environmental factors that disrupt hepatic identity and function. Developmental signals and fetal genetic programmes are often dysregulated or reactivated, leading to dedifferentiation and disease. Here, we highlight signalling pathways and transcriptional regulators that drive liver cell development and primary liver cancers. We also discuss emerging models derived from pluripotent stem cells, 3D organoids and bioengineering for improved studies of signalling pathways in liver cancer and regenerative medicine.
In 2018, the U.S. military developed the Military Acute Concussion Evaluation-2 (MACE-2) to inform acute evaluation of mTBI. However, researchers have yet to investigate false positive rates for components of the MACE-2 including the Vestibular-Ocular Motor Screen (VOMS) and modified Balance Error Scoring System (mBESS) in military personnel.

To examine factors associated with false positives in VOMS and mBESS in U.S. Army Special Operations Command (USASOC) personnel.

Cross-sectional study.

Military medical clinic.

416 healthy USASOC personnel completed medical history, VOMS, and mBESS evaluations.

False positive rates for the VOMS (2+ on VOMS symptom item, ≥ 5 cm for near point of convergence [NPC] distance) and mBESS (total score >4) were determined using chi-square analyses and independent samples t-tests. Multivariable logistic regressions (LR) with adjusted odds ratios (aOR) were performed to identify risk factors for false positives on VOMS and mBESS. VOMS items false positive rates rangge, history of mTBI, migraine, and motion sickness. False positives for the mBESS total score were higher (36.5%) and were only associated with a history of motion sickness. These risk factors for false positives should be considered when administering and interpreting VOMS and mBESS components of the MACE-2 in this population.Cancer-related financial hardship is highly prevalent and affects individuals in the setting of cancer care delivery across the survivorship trajectory. Mitigating financial hardship requires multi-level solutions at the policy, payer, health-care system, provider, and individual patient levels. At the highest level, strategies for intervention include enacting policies to improve price transparency and expand insurance coverage. Also needed are implementing systematic screening and financial navigation in cancer care delivery; improving cost communication by provider care teams; developing patient-reported measures that incorporate the multiple, complex dimensions of financial hardship, as reflected in the Economic Strain and Resilience in Cancer tool; and advancing electronic medical record infrastructure to manage data on patient financial hardship. For individual patients, activating their social networks, community resources, and employers provides patient-level support resources to enhance coping. The proposed multi-level approach is needed to overcome financial hardship in the setting of high-quality, high-value cancer care delivery.Fifteen years ago, the Institute of Medicine (IOM) issued a report that defined Survivorship Care as a distinct phase of the cancer care continuum. The required domains to meet the health needs of cancer survivors were outlined in the report cancer surveillance and screening, cancer prevention and lifestyle counseling, management of treatment related persistent or late effects, coordination of care, and psychosocial support services. In response to that report, The University of Texas MD Anderson Cancer Center implemented a tiered survivorship care model that is risk based. The core principle is that cancer survivors' health needs will depend on the cancer treatment and disease-specific risks. We here describe this model for low-, intermediate-, and high-risk cancer survivors, in which comanagement between oncology and primary care providers is risk dependent. Our clinical model defines transition as appropriate when there is a minimal risk of primary cancer relapse, which is specific to each cancer type and disease stage. This model is embedded into disease-specific clinical practice algorithms, aligned with the IOM domains of care. Over the past 10 years, we have successfully transitioned nearly 25 000 patients to disease-specific survivorship clinics, providing care based on the IOM domains. We have learned from our process that expansion of survivorship care into established clinical settings requires engagement of champions and key clinical stakeholders. Future directions for survivorship care should explore the application and potential benefits of telemedicine as a care delivery system to meet the needs of cancer survivors.New models of survivorship care are needed that improve outcomes for the growing number of cancer survivors, address the increasing complexity of their health needs, and deal with the shortage of clinicians and rising costs of this care. Technology can aid the delivery of personalized, stratified survivorship care pathways where the intensity of care, the care setting, and the providers required for that care vary with survivors' needs. Building a cancer data ecosystem of connected data streams that supports and learns from each patient can be used to streamline care, enhance efficiency, reduce costs, and facilitate research. This manuscript describes the input, analytics, and output components of the cancer data ecosystem that must be built and connected and also provides a real-world use case of how such a system could transform care in a large US comprehensive cancer center.Patient-reported outcomes play an essential role in improving care across the cancer continuum. This paper reports on the experience of a tertiary care center to standardize the use, collection, and reporting of patient-reported outcomes (PROs) in 10 disease-specific survivorship clinics. To minimize the burden of patients to complete surveys, an institutional committee with oversight on all patient surveys required an application be reviewed and approved before their distribution in a clinic. To begin collecting PROs, each clinic submitted an application tailored to its clinical operations, staffing, and scheduling characteristics. The dates for the submission of each application were staggered over a 2-year period, which contributed to a lack of uniformity in the project (ie, approval dates, start dates, collection and reporting of results). The delays were primarily due to the time and resources required to build the electronic version of the PRO survey into the institutional electronic medical record. To date, 6 of 10 survivorship clinics submitted applications, 5 were approved, and 4 launched the electronic MD Anderson Symptom Inventory (eMDASI) through the patient portal. Metrics collected between January 2019 and December 2020 for the thyroid, bone marrow transplant, genitourinary, and head and neck clinics indicated the numbers of eMDASIs sent to patients varied by clinic, with the lowest from the bone marrow transplant survivorship clinic (6) and the highest (746) in the thyroid Clinic. The total number of eMDASIs returned by the patients ranged from 2 (bone marrow transplant) to 429 (thyroid). Overall, patients' return rates of the eMDASI ranged from 33.3% to 57.7%. Several strategies were implemented to increase the delivery, submission, and completion of eMDASIs. Our findings indicate the integration and implementation of PROs in survivorship clinics are achievable. Further work is needed to enhance the ePROs web-based process to adequately compare PROs across diverse cohorts of cancer survivors .In 2006, the Institute of Medicine recognized that cancer survivors faced complex physical and emotional health problems, often overlooked or inadequately managed. In Texas, access to programs specifically designed to address unique needs of cancer survivors is almost nonexistent for low-income uninsured or underinsured patients. In response to the unmet care needs of underserved cancer centers, Moncrief Cancer Institute, an affiliate of the National Cancer Institute-designated UT Southwestern Harold C. Simmons Comprehensive Cancer Center, established a community-based program using a survivorship care model similar to those offered in academic medical centers. Understanding that a one-size-fits-all approach could not successfully meet the needs across the service area, the cancer survivorship service line was mobilized to provide flexibility in delivery without sacrificing quality of care. The program continues to evolve, extending the foremost scientific information and resources into the communities it serves.Adolescents and young adults with cancer have an estimated 5-year overall survival rate of more than 75%. It can be difficult to immediately return to a "normal" life after cancer therapy because of a range of physical and psychosocial effects associated not only to the disease but also to late effects that can extend long into survivorship. Adolescents and young adult cancer survivors in the United States are more prone to several adverse treatment effects than those who had no history of cancer. A multidisciplinary health-care team that is well versed in caring for specific developmental issues, as well as addressing onco-fertility, psychosocial and socioeconomic issues, school and work obligations, and long-term side effects is important to meet the needs of this population.
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