The University of Texas Southwestern Medical Center (UT Southwestern or UTSW) is a public academic health science center in Dallas, Texas. With approximately 13,568 employees and 2,445 faculty and over 2.7 million outpatient visits per year, UT Southwestern is the largest medical school in the University of Texas System and state of Texas.UTSW's operating budget in 2019 was more than $3.152 billion, and is the largest medical institution in the Dallas Metroplex (and therefore north Texas), annually training about 3,700 medical, graduate, and health professions students, residents, and postdoctoral fellows. Ongoing support from outside sources provides approximately $422.6 million per year for more than 5,700 research projects. In 2017, the school had the largest federal expenditure funding of all UT medical institutions at $204.5 million.UTSW's three-part mission is to: educate leaders in patient care, biomedical science, and disease prevention; conduct research; and deliver patient care. It incorporates three major degree-granting institutions – UT Southwestern Medical School, UT Southwestern Graduate School of Biomedical Sciences, and UT Southwestern School of Health Professions. UTSW has four major affiliated hospitals: Parkland Memorial Hospital, Dallas Children's Medical Center, Zale Lipshy Pavilion – William P. Clements Jr. University Hospital, and William P. Clements Jr. University Hospital. However UT Southwestern's faculty also provide services at Texas Scottish Rite Hospital for Children, VA North Texas Health Care System, and other affiliated hospitals and community clinics in the Metroplex. Faculty and residents care for more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year, including more than $106.7 million in unreimbursed clinical services annually. Through the four major hospitals affiliated with UT, the medical center also has a large presence in Plano and Frisco, prominent suburbs in the Dallas area. Furthermore, in 2016, UT Southwestern began providing additional care through Southwestern Health Resources, a new network combining the systems of Texas Health Resources and UT Southwestern. The network comprises 27 hospitals, 300 clinics, and more than 2,000 physicians, serving a 16-county area with more than 6 million residents.
Alterations in chromatin remodeling genes have been increasingly implicated in human oncogenesis. Specifically, the biallelic inactivation of the SWI/SNF subunit SMARCB1 results in the emergence of extremely aggressive pediatric malignancies. Here, we developed embryonic mosaic mouse models of malignant rhabdoid tumors (MRTs) that faithfully recapitulate the clinical-pathological features of the human disease. We demonstrated that SMARCB1-deficient malignancies exhibit dramatic activation of the unfolded protein response (UPR) and ER stress response via a genetically intact MYC-p19ARF-p53 axis. As a consequence, these tumors display an exquisite sensitivity to agents inducing proteotoxic stress and inhibition of the autophagic machinery. In conclusion, our findings provide a rationale for drug repositioning trials investigating combinations of agents targeting the UPR and autophagy in SMARCB1-deficient MRTs.
This review summarizes considerations within the existing recent literature that guide the practice of interval appendectomy (IA) after initial non-operative management (NOM) of complicated appendicitis (CA) in children. A systematic review of English language articles published from 2000 to 2025 was conducted in Medline, Embase, and Cochrane Central Register of Controlled Trials to address four elements which could impact the decision for IA after NOM of CA: (1) the incidence of recurrent appendicitis; (2) the time period in which recurrence occurs; (3) the patient or disease-related risk factors which increase recurrence; and (4) the incidence of appendiceal neoplasms identified by IA. Of the 3,022 articles initially reviewed, 46 met inclusion criteria. Recurrence was reported in 2–50
Persons with disorders of consciousness (DoC) occupy an ethically charged space in modern medicine and biomedical research. Their decisional capacity is characteristically absent or limited or unpredictably fluctuates, requiring clinicians and investigators to rely on surrogates. Although there is general guidance for informed consent (IC) for research studies, there is no specific guidance for research involving persons with DoC. There are inconsistencies in IC forms for these studies related to explanation of a DoC, evaluation of capacity, description of risks/benefits, and sharing investigational results. This is problematic for persons with DoC, their surrogates, researchers, and institutional review boards (IRBs)/research ethics boards (REBs). To address these issues, the Curing Coma Campaign (CCC) Ethics Workgroup developed the Common Consent Elements for Research Involving Persons with Disorders of Consciousness (CCE-DoC). This practical framework aims to clarify and standardize consent processes in this complex and ethically sensitive research area. Through this structured, adaptable approach, CCE-DoC may have the potential to enhance participant protections, strengthen trust, help families and decision-makers understand studies, reduce duplicative efforts across research groups, and guide investigators and IRBs/REBs in navigating the complex ethical terrain of consent in DoC research. In so doing, CCE-DoC seeks to extend respect for autonomy and trust and promote responsible research urgently needed to advance paradigms of diagnosis, prognosis, and treatment for individuals with disorders of consciousness. The framework offers example language to encourage standardization, while allowing teams flexibility to customize to local needs.
BackgroundThe Lynch syndrome INtegrative Epidemiology And GEnetics (LINEAGE) consortium was established to address gaps in understanding genotype-specific cancer risks and risk-modifiers in contemporary North American Lynch syndrome (LS) populations. LINEAGE is a multi-center, longitudinal cohort to systematically collect data on risk factors, adherence to care, quality of surveillance, and patient-, provider-, and system-level factors associated with incident LS-associated cancers.MethodsLINEAGE recruits individuals with confirmed pathogenic or likely pathogenic variants in LS-associated genes from participating institutions. Data includes retrospective and prospective collection, encompassing clinical abstraction (demographics, surgical history, endoscopic data, treatments), patient-reported surveys (behavioral/lifestyle factors, quality of life, procedures), endoscopist-level data, and biosample metadata. A standardized REDCap database, data harmonization protocols, and a virtual biobank support reproducibility and linkage of clinical data and biosamples. Rigorous quality assurance/quality control processes are embedded for data integrity.ResultsParticipating centers will contribute data to determine gene-specific risks, and gene-environment interactions for Lynch-associated, and other cancers. We will evaluate associations with exposure to, and quality of cancer risk-reduction care, including endoscopic surveillance, risk-reduction surgery, and chemoprevention. The inclusion of provider-level variables, such as endoscopist training and experience, enables unique research into modifiers of post-endoscopy cancer risk. The linked biosample resources will further facilitate mechanistic studies and biomarker discovery.ConclusionsLINEAGE provides a robust platform for advancing LS research by integration of clinical, pathological, epidemiological and genetic data across institutions. Its standardized, collaborative framework enhances the validity and generalizability of risk estimates that will guide decision-making and policy for surveillance to ultimately reduce morbidity and mortality for individuals with Lynch syndrome.
