Larotrectinib Treatment for Patients With TRK Fusion-Positive Salivary Gland Cancers.

Background: Larotrectinib is a first-in-class, highly selective, and central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for the treatment of adult and pediatric patients with TRK fusion cancer. We report the efficacy and safety of larotrectinib in patients with TRK fusion-positive salivary gland cancers.

Patients And Methods: Patients with TRK fusion-positive salivary gland cancer treated with larotrectinib were identified from two clinical trials (NCT02122913 and NCT02576431).

A Path Toward Health Care Equity: System-Based Interventions for Change.

Despite documentation spanning decades, health care disparities across North Carolina have remained persistent for populations of color, especially for Black patients. This commentary reviews recent studies that used system-based interventions to reduce disparities and improve outcomes for everyone, and outlines how clinicians, partnering with NC AHEC, can apply results to practice.

Desiccation-tolerance and globular proteins adsorb similar amounts of water.

When exposed to desiccation stress, extremotolerant organisms from all domains of life produce protective disordered proteins with the potential to inform the design of excipients for formulating biologics and industrial enzymes. However, the mechanism(s) of desiccation protection remain largely unknown. To investigate the role of water sorption in desiccation protection, we use thermogravimetric analysis to study water adsorption by two desiccation-tolerance proteins, cytosolic abundant heat soluble protein D from tardigrades and late embryogenesis abundant protein 4 from the anhydrobiotic midge Polypedilum vanderplanki, and, as a control, the globular B1 domain of staphylococcal protein G.

EatWellNow: Formative Development of a Place-Based Behavioral "Nudge" Technology Intervention to Promote Healthier Food Purchases among Army Soldiers.

Approximately 17% of military service members are obese. Research involving army soldiers suggests a lack of awareness of healthy foods on post. Innovative approaches are needed to change interactions with the military food environment.

Risk of intra-abdominal seeding after laparoscopic-assisted thermal ablation of exophytic hepatocellular carcinoma tumors.

Background: Laparoscopic-assisted thermal ablation has been used successfully to treat early hepatocellular carcinoma (HCC) tumors, defined as < 3 cm in diameter. This approach allows for ablation of tumors located in areas of the liver that are otherwise inaccessible for a percutaneous approach. Thermal ablation of exophytic tumors remains controversial due to a reported increased risk of tumor seeding of the abdominal cavity and incomplete ablation.

Impact of adherence to ibrutinib on clinical outcomes in real-world patients with chronic lymphocytic leukemia.

Ibrutinib is an oral Bruton's tyrosine kinase inhibitor approved for treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Clinical trial data suggest that strict adherence is directly related to clinical outcomes. This retrospective, multicenter study aimed to evaluate ibrutinib adherence and its impact on clinical outcomes in patients with CLL/SLL treated in the real-world setting.

High-Risk Human Papillomavirus Messenger RNA Testing Using Urine, Cervicovaginal Self-Collected and Provider-Collected Cervical Samples Among Women in Mombasa, Kenya.

We compared human papillomavirus messenger RNA testing using urine, self-, and provider-collected samples for the detection of high-grade cervical cytology and assessed acceptability of urine self-collection among females who engage in sex work in Kenya. Participants found urine sampling comfortable, but high-risk human papillomavirus messenger RNA detection in urine samples was less likely to detect high-grade lesions than self- and provider-collected cervical samples.

Quantitative profiling of adaptation to cyclin E overproduction.

Cyclin E/CDK2 drives cell cycle progression from G1 to S phase. Despite the toxicity of cyclin E overproduction in mammalian cells, the cyclin E gene is overexpressed in some cancers. To further understand how cells can tolerate high cyclin E, we characterized non-transformed epithelial cells subjected to chronic cyclin E overproduction.

Age Profiles of Cognitive Decline and Dementia in Late Life in the Aging, Demographics, and Memory Study.

Objectives: To better understand the temporal dynamics of progression from cognitive decline to onset of dementia in the dementia-free older population in the United States.

Methods: We used longitudinal data from a diverse national population-based sample of older adults (N = 531) in the Aging, Demographics, and Memory Study from the Health and Retirement Study with repeated measures of cognitive function and dementia diagnosis during 12 years of follow-up from 1996 to 2009. We employed joint latent class mixed models to estimate the association between cognitive change and competing risks of dementia and nondementia death and identify heterogeneity in the age profiles of such association adjusting for baseline characteristics.

Cell membrane-anchored and tumor-targeted IL-12 (attIL12)-T cell therapy for eliminating large and heterogeneous solid tumors.

Background: Adoptive T-cell transfer has become an attractive therapeutic approach for hematological malignancies but shows poor activity against large and heterogeneous solid tumors. Interleukin-12 (IL-12) exhibits potent antitumor efficacy against solid tumors, but its clinical application has been stalled because of toxicity. Here, we aimed to develop a safe approach to IL-12 T-cell therapy for eliminating large solid tumors.

eSyM: An Electronic Health Record-Integrated Patient-Reported Outcomes-Based Cancer Symptom Management Program Used by Six Diverse Health Systems.

Purpose: Collecting patient-reported outcomes (PROs) can improve symptom control and quality of life, enhance doctor-patient communication, and reduce acute care needs for patients with cancer. Digital solutions facilitate PRO collection, but without robust electronic health record (EHR) integration, effective deployment can be hampered by low patient and clinician engagement and high development and deployment costs. The important components of digital PRO platforms have been defined, but procedures for implementing integrated solutions are not readily available.

Fibrinogen improves liver function via promoting cell aggregation and fibronectin assembly in hepatic spheroids.

Many key functions performed by the liver depend on the interaction between parenchymal cells and the microenvironment comprised of neighboring cells and extracellular matrix. The biological macromolecules in the matrix, which are dynamically changing, participate in various physiological processes through interactions with cell surface receptors, antigens, and ion channels. We found the rat liver biomatrix scaffold (LBS) prepared from adult rats is more effective in enhancing the function of hepatic spheroids than those derived from newborn or senile rats.

Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors.

Background: Larotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved to treat adult and pediatric patients with TRK fusion-positive cancer. The aim of this study was to evaluate the efficacy and safety of larotrectinib in patients with TRK fusion-positive primary central nervous system (CNS) tumors.

Methods: Patients with TRK fusion-positive primary CNS tumors from two clinical trials (NCT02637687, NCT02576431) were identified.

FGFR1 Overexpression Induces Cancer Cell Stemness and Enhanced Akt/Erk-ER Signaling to Promote Palbociclib Resistance in Luminal A Breast Cancer Cells.

Resistance to CDK4/6 inhibitors (CDKis) is emerging as a clinical challenge. Identification of the factors contributing to CDKi resistance, with mechanistic insight, is of pivotal significance. Recent studies linked aberrant FGFR signaling to CDKi resistance.

PKCθ-mediated serine/threonine phosphorylations of FAK govern adhesion and protrusion dynamics within the lamellipodia of migrating breast cancer cells.

The cytoskeleton and cell-matrix adhesions constitute a dynamic network that controls cellular behavior during development and cancer. The Focal Adhesion Kinase (FAK) is a central actor of these cell dynamics, promoting cell-matrix adhesion turnover and active membrane fluctuations. However, the initial steps leading to FAK activation and subsequent promotion of cell dynamics remain elusive.

Protection by desiccation-tolerance proteins probed at the residue level.

Extremotolerant organisms from all domains of life produce protective intrinsically disordered proteins (IDPs) in response to desiccation stress. In vitro, many of these IDPs protect enzymes from dehydration stress better than U.S.

Testing for Sexually Transmitted Infection Using Wet and Dry Self-Collected Brush Samples Among Women in Mombasa, Kenya.

We compared detection of Chlamydia trachomatis , Neisseria gonorrhoeae , and Trichomonas vaginalis using dry and wet self-collected samples using brushes among females who engage in sex work in Mombasa, Kenya. Detection of T. vaginalis and N.

Regulation of local GTP availability controls RAC1 activity and cell invasion.

Physiological changes in GTP levels in live cells have never been considered a regulatory step of RAC1 activation because intracellular GTP concentration (determined by chromatography or mass spectrometry) was shown to be substantially higher than the in vitro RAC1 GTP dissociation constant (RAC1-GTP Kd). Here, by combining genetically encoded GTP biosensors and a RAC1 activity biosensor, we demonstrated that GTP levels fluctuating around RAC1-GTP Kd correlated with changes in RAC1 activity in live cells. Furthermore, RAC1 co-localized in protrusions of invading cells with several guanylate metabolism enzymes, including rate-limiting inosine monophosphate dehydrogenase 2 (IMPDH2), which was partially due to direct RAC1-IMPDH2 interaction.

Schizophrenia-Linked Protein tSNARE1 Regulates Endosomal Trafficking in Cortical Neurons.

, which encodes the protein tSNARE1, is a high-confidence gene candidate for schizophrenia risk, but nothing is known about its cellular or physiological function. We identified the major gene products of and their cytoplasmic localization and function in endosomal trafficking in cortical neurons. We validated three primary isoforms of expressed in human brain, all of which encode a syntaxin-like Qa SNARE domain.

Sex Differences in the Association Between Metabolic Dysregulation and Cognitive Aging: The Health and Retirement Study.

Background: Dysregulation of some metabolic factors increases the risk of dementia. It remains unclear if overall metabolic dysregulation, or only certain components, contribute to cognitive aging and if these associations are sex specific.

Methods: Data from the 2006-2016 waves of the Health and Retirement Study (HRS) was used to analyze 7 103 participants aged 65 and older at baseline (58% women).

Water's Variable Role in Protein Stability Uncovered by Liquid-Observed Vapor Exchange NMR.

Water is essential to protein structure and stability, yet our understanding of how water shapes proteins is far from thorough. Our incomplete knowledge of protein-water interactions is due in part to a long-standing technological inability to assess experimentally how water removal impacts local protein structure. It is now possible to obtain residue-level information on dehydrated protein structures via liquid-observed vapor exchange (LOVE) NMR, a solution NMR technique that quantifies the extent of hydrogen-deuterium exchange between unprotected amide protons of a dehydrated protein and DO vapor.

Immune function, cortisol, and cognitive decline & dementia in an aging latino population.

Background: The etiology of dementias and cognitive decline remain largely unknown. It is widely accepted that inflammation in the central nervous system plays a critical role in the pathogenesis of dementia. However, less is known about the role of the peripheral immune system and interactions with cortisol, though evidence suggests that these, too, may play a role.

Dietary Vitamin A and Breast Cancer Risk in Black Women: The African American Breast Cancer Epidemiology and Risk (AMBER) Consortium.

Background: Studies in women of European descent showed an inverse association of dietary vitamin A (retinol and carotenoids) intake with breast cancer risks, mainly in premenopausal women.

Objectives: We examined whether higher compared with lower levels of dietary vitamin A are associated with reduced breast cancer risks among Black women by estrogen receptor (ER) and menopausal statuses.

Methods: In this pooled analysis, data were from 3564 breast cancer cases and 11,843 controls (mean ages = 56.