Targeting rapid TKI-induced AXL upregulation overcomes adaptive ERK reactivation and exerts antileukemic effects in FLT3/ITD acute myeloid leukemia.

Acute myeloid leukemia (AML) patients with the FMS-related receptor tyrosine kinase 3 internal tandem duplication (FLT3/ITD) mutation have a poorer prognosis, and treatment with FLT3 tyrosine kinase inhibitors (TKIs) has been hindered by resistance mechanisms. One such mechanism is known as adaptive resistance, in which downstream signaling pathways are reactivated after initial inhibition. Past work has shown that FLT3/ITD cells undergo adaptive resistance through the reactivation of extracellular signal-regulated kinase (ERK) signaling within 24 h of sustained FLT3 inhibition.

Identification and biophysical characterization of epitope atlas of Porcine Reproductive and Respiratory Syndrome Virus.

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) have been a critical threat to swine health since 1987 due to its high mutation rate and substantial economic loss over half a billion dollar in USA. The rapid mutation rate of PRRSV presents a significant challenge in developing an effective vaccine. Even though surveillance and intervention studies have recently (2019) unveiled utilization of PRRSV glycoprotein 5 (GP5; encoded by gene) to induce immunogenic reaction and production of neutralizing antibodies in porcine populations, the future viral generations can accrue escape mutations.

Quantitative methods for optimizing patient outcomes in liver transplantation.

Liver transplantation (LT) is a lifesaving yet complex intervention with considerable challenges impacting graft and patient outcomes. Despite best practices, 5-year graft survival is only 70%. Sophisticated quantitative techniques offer potential solutions by assimilating multifaceted data into insights exceeding human cognition.

Aligning the Central Brain Tumor Registry of the United States (CBTRUS) histology groupings with current definitions.

Background: The Central Brain Tumor Registry of the United States (CBTRUS) uses a histology grouping model based on the World Health Organization (WHO) classifications to group records for clinically relevant statistical reporting. Newly identified genetic markers more accurately stratify patients than histology alone and were incorporated into the 2016 update to the WHO Classification.

Methods: CBTRUS and consulting neuropathologists reviewed and aligned histology groupings with the 2016 WHO update.

New Approaches to the Diagnosis of Rejection and Prediction of Tolerance in Liver Transplantation.

Immunosuppression after liver transplantation is essential for preventing allograft rejection. However, long-term drug toxicity and associated complications necessitate investigation of immunosuppression minimization and withdrawal protocols. Development of such protocols is hindered by reliance on current paradigms for monitoring allograft function and rejection status.

Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission.

As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing.

Tag-based spite with correlated interactions.

We use evolutionary game theory to study the evolution of harming behavior (spite) in settings involving both tags and (anti-) correlated interaction. Our results show an interesting interaction between these mechanisms. The presence of tags shows that pure spite is less likely to evolve when theoretically expected, but that conditional spite is more likely than expected.

Progress and challenges in diagnosis and treatment of rejection following liver transplantation.

Purpose Of Review: Liver biopsy remains the most widely utilized method for diagnosis of allograft rejection following liver transplantation. However, associated risks and limitations present an opportunity for emerging noninvasive diagnostic techniques to improve upon the current standard of care. This review evaluates progress toward development of new noninvasive methods for the monitoring and diagnosing of allograft rejection.

Communication without common interest: A signaling experiment.

Communication can arise when the interests of speaker and listener diverge if the cost of signaling is high enough that it aligns their interests. But what happens when the cost of signaling is not sufficient to align their interests? Using methods from experimental economics, we test whether theoretical predictions of a partially informative system of communication are borne out. As our results indicate, partial communication can occur even when interests do not coincide.

Coordination, conflict, and externalization.

I argue that the set of moralized norms and beliefs is more expansive than Stanford appears to suggest. In particular, I contend that norms governing behavior in conflictual coordination problems are likely to be moralized.

Musculoskeletal Disorders in Ophthalmologists After Simulated Cataract Operation: A Pilot Study.

Context: Musculoskeletal disorders are a common problem among ophthalmologists, likely due to ergonomic challenges. Most research on the topic has been survey-based studies, which carry inherent weaknesses.

Objective: To examine the frequency and pattern of musculoskeletal dysfunction induced by performing a surgical procedure and to quantify the improvement after ergonomic interventions.

Adaptation to TKI Treatment Reactivates ERK Signaling in Tyrosine Kinase-Driven Leukemias and Other Malignancies.

FMS-like tyrosine kinase-3 (FLT3) tyrosine kinase inhibitors (TKI) have been tested extensively to limited benefit in acute myeloid leukemia (AML). We hypothesized that FLT3/internal tandem duplication (ITD) leukemia cells exhibit mechanisms of intrinsic signaling adaptation to TKI treatment that are associated with an incomplete response. Here, we identified reactivation of ERK signaling within hours following treatment of FLT3/ITD AML cells with selective inhibitors of FLT3.

The Utility of Expert Diagnosis in Surgical Neuropathology: Analysis of Consultations Reviewed at 5 National Comprehensive Cancer Network Institutions.

The aim of this study was to characterize the type and degree of discrepancies between non-expert and expert diagnoses of CNS tumors to identify the value of consultations in surgical neuropathology. Neuropathology experts from 5 National Comprehensive Cancer Network (NCCN) member institutions participated in the review of 1281 consultations selected based on inclusion criteria. The consultation cases were re-reviewed at the NCCN headquarters to determine concordance with the original diagnoses.

Looking for the Silver Lining: Benefit Finding after Hurricanes Katrina and Rita in Middle-Aged, Older, and Oldest-Old Adults.

Looking for potentially positive outcomes is one way that people cope with stressful events. In two studies, we examined perceived "silver linings" after the 2005 Hurricanes Katrina and Rita among indirectly affected adults. In Study 1, middle-aged (ages 47-64 years), older (ages 65-89 years), and oldest-old (ages 90-95 years) adults in the Louisiana Healthy Aging Study (LHAS) responded to an open-ended question on perceived silver linings in a longitudinal assessment carried out during the immediate impact (1 to 4 months after landfall) and post-disaster recovery phase (6 to 14 months post-storm).

All-trans retinoic acid synergizes with FLT3 inhibition to eliminate FLT3/ITD+ leukemia stem cells in vitro and in vivo.

FMS-like tyrosine kinase 3 (FLT3)-mutant acute myeloid leukemia (AML) portends a poor prognosis, and ineffective targeting of the leukemic stem cell (LSC) population remains one of several obstacles in treating this disease. All-trans retinoic acid (ATRA) has been used in several clinical trials for the treatment of nonpromyelocytic AML with limited clinical activity observed. FLT3 tyrosine kinase inhibitors (TKIs) used as monotherapy also achieve limited clinical responses and are thus far unable to affect cure rates in AML patients.

Glioblastoma-infiltrated innate immune cells resemble M0 macrophage phenotype.

Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms by which glioblastoma-associated myeloid cells (GAMs) undergo metamorphosis into tumor-supportive cells, characterizing the heterogeneity of immune cell phenotypes within glioblastoma subtypes, and discovering new targets can help the design of new efficient immunotherapies. In this study, we performed a comprehensive battery of immune phenotyping, whole-genome microarray analysis, and microRNA expression profiling of GAMs with matched blood monocytes, healthy donor monocytes, normal brain microglia, nonpolarized M0 macrophages, and polarized M1, M2a, M2c macrophages.

Cartographic Mapping and Travel Burden to Assess and Develop Strategies to Improve Minority Access to National Cancer Clinical Trials.

Purpose: To assess how accrual to clinical trials is related to US minority population density relative to clinical trial site location and distance traveled to Radiation Therapy Oncology Group (RTOG) clinical trial sites.

Methods And Materials: Data included member site address and ZIP codes, patient accrual, and patient race or ethnicity and ZIP code. Geographic Information System maps were developed for overall, Latino, and African American accrual to trials by population density.

Adult brainstem gliomas: Correlation of clinical and molecular features.

Background: Brainstem gliomas are rare in adults and overall have superior survival outcomes compared to pediatric brainstem gliomas.

Patients And Methods: We conducted a retrospective data and tissue analysis of all adult patients (≥ 18 years old) with World Health Organization (WHO) Grade II, III, and IV brainstem gliomas in the University of Texas MD Anderson Cancer Center institutional database from 1990 to 2012.

Results: We identified 143 cases in adults ages 18 and over.

Characterization of pseudoprogression in patients with glioblastoma: is histology the gold standard?

Pseudoprogression (psPD) refers to an increase in size or appearance of new areas of MRI contrast enhancement soon after completing chemoradiation, timely diagnosis of which has been a challenge. Given that tissue sampling of the MRI changes would be expected to accurately distinguish psPD from true progression when MRI changes are first seen, we examined the utility of surgery in diagnosing psPD and influencing patient outcome. We retrospectively reviewed data from adults with GBM who had MRI changes suggestive of progression within 3 months of chemoRT; of these, 34 underwent surgical resection.

Primary rhabdomyosarcoma of the pineal gland.

Objectives: To report a case of primary rhabdomyosarcoma (RMS) of the pineal gland in an adult, as well as review the literature on this rare entity.

Methods: The case is compared with previous reports of similar entities, with emphasis on this patient's characteristics and clinical presentation, investigations, and management.

Results: Diagnosis of primary RMS of the pineal gland was based on the presence of strap cells and multinucleated myotube-like structures, as well as tumor cell expression of skeletal muscle markers consistent with myogenic differentiation.

Postoperative singultus: an osteopathic approach.

Singultus, or hiccups, is a common medical condition. Despite exponential leaps in medicine, the pathophysiologic cause remains poorly defined. Persistent singultus has been associated with conditions such as pulmonary embolism and myocardial infarction.

Development and validation of the Patriarchal Beliefs Scale.

The purpose of this research was to develop and validate a conceptually and psychometrically solid measure for patriarchal beliefs in samples of U.S. American adults from diverse demographic and geographic backgrounds.

Extraskeletal myxoid chondrosarcoma presenting as an intradural spinal mass: report of a rare clinical presentation with an emphasis on differential diagnostic considerations.

Extraskeletal myxoid chondrosarcoma is a rare soft tissue neoplasm that occurs predominantly in the soft tissues of the lower extremities. Herein we present a case of a 29 year old male who presented with bilateral femoral numbness believed to be the result of prior injury to his back. A magnetic resonance imaging revealed a mass in the T4-T5 epidural space compressing the spinal cord.