Publications

Take a deeper look into all the publications produced by researchers at The Dartmouth Institute.

Loh TP, Cervinski MA, Katayev A, Bietenbeck A, van Rossum H, Badrick T, International Federation of Clinical Chemistry and Laboratory Medicine Committee on Analytical Quality.

2019 Jun 10;pii: S0009-8981(19)31901-1. doi: 10.1016/j.cca.2019.06.009

Patient based real time Quality Control (PBRTQC) algorithms provide many advantages over conventional QC approaches including lower cost, absence of commutability problems, continuous real-time monitoring of performance, and sensitivity to pre-analytical error. However, PBRTQC is not as simple to implement as conventional QC because of the requirement to access patient data as well as setting up appropriate rules, action protocols, and choosing best statistical algorithms. These requirements need capable and flexible laboratory informatics (middleware). In this document, the necessary features of software packages needed to support PBRTQC are discussed as well as recommendations for optimal integration of this technique into laboratory practice.

Clin Chim Acta|2019 Jun 10

Tian A, Duwadi D, Benchabane H, Ahmed Y

2019 Jun;15(6):e1008111doi: 10.1371/journal.pgen.1008111

Signal transduction activated by Wingless/Wnt ligands directs cell proliferation and fate specification in metazoans, and its overactivation underlies the development of the vast majority of colorectal cancers. In the conventional model, the secretion and movement of Wingless to cells distant from its source of synthesis are essential for long-range signaling in tissue patterning. However, this model was upended recently by an unanticipated finding: replacement of wild-type Drosophila Wingless with a membrane-tethered form produced viable adults with largely normal external morphology, which suggested that Wingless secretion and movement are dispensable for tissue patterning. Herein, we tested this foundational principle in the adult intestine, where Wingless signaling gradients coincide with all major boundaries between compartments. We find that the critical roles of Wingless during adult intestinal development, which include regulation of target gene activation, boundary formation, stem cell proliferation, epithelial cell fate specification, muscle differentiation, gut folding, and signaling crosstalk with the Decapentaplegic pathway, are all disrupted by Wingless tethering. These findings provide new evidence that supports the requirement for the direct, long-range action of Wingless in tissue patterning, with relevance for animal development, tissue homeostasis and Wnt-driven disease.

PLoS Genet|2019 Jun

Everts PA, Malanga GA, Paul RV, Rothenberg JB, Stephens N, Mautner KR

2019 Dec;11:56-64doi: 10.1016/j.reth.2019.03.009

Autologous biologics, defined as platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMC), are cell-based therapy treatment options in regenerative medicine practices, and have been increasingly used in orthopedics, sports medicine, and spinal disorders. These biological products are produced at point-of-care; thereby, avoiding expensive and cumbersome culturing and expansion techniques. Numerous commercial PRP and BMC systems are available but reports and knowledge of bio-cellular formulations produced by these systems are limited. This limited information hinders evaluating clinical and research outcomes and thus making conclusions about their biological effectiveness. Some of their important cellular and protein properties have not been characterized, which is critical for understanding the mechanisms of actions involved in tissue regenerative processes. The presence and role of red blood cells (RBCs) in any biologic has not been addressed extensively. Furthermore, some of the pathophysiological effects and phenomena related to RBCs have not been studied. A lack of a complete understanding of all of the biological components and their functional consequences hampers the development of clinical standards for any biological preparation. This paper aims to review the clinical implications and pathophysiological effects of RBCs in PRP and BMC; emphasizes hemolysis, eryptosis, and the release of macrophage inhibitory factor; and explains several effects on the microenvironment, such as inflammation, oxidative stress, vasoconstriction, and impaired cell metabolism.

Regen Ther|2019 Dec

Bridge JA, Sumegi J, Druta M, Bui MM, Henderson-Jackson E, Linos K, Baker M, Walko CM, Millis S, Brohl AS

2019 Jun 12;doi: 10.1038/s41379-019-0301-1

Molecular diagnostics of sarcoma subtypes commonly involve the identification of characteristic oncogenic fusions. EWSR1-PATZ1 is a rare fusion partnering in sarcoma, with few cases reported in the literature. In the current study, a series of 11 cases of EWSR1-PATZ1 fusion positive malignancies are described. EWSR1-PATZ1-related sarcomas occur across a wide age range and have a strong predilection for chest wall primary site. Secondary driver mutations in cell-cycle genes, and in particular CDKN2A (71%), are common in EWSR1-PATZ1 sarcomas in this series. In a subset of cases, an extended clinical and histopathological review was performed, as was confirmation and characterization of the fusion breakpoint revealing a novel intronic pseudoexon sequence insertion. Unified by a shared gene fusion, EWSR1-PATZ1 sarcomas otherwise appear to exhibit divergent morphology, a polyphenotypic immunoprofile, and variable clinical behavior posing challenges for precise classification.

Mod Pathol|2019 Jun 12

Pilarski JQ, Leiter JC, Fregosi RF

2019 Jun 12;9(3):1025-1080doi: 10.1002/cphy.c180008

This review is a comprehensive description of all muscles that assist lung inflation or deflation in any way. The developmental origin, anatomical orientation, mechanical action, innervation, and pattern of activation are described for each respiratory muscle fulfilling this broad definition. In addition, the circumstances in which each muscle is called upon to assist ventilation are discussed. The number of "respiratory" muscles is large, and the coordination of respiratory muscles with "nonrespiratory" muscles and in nonrespiratory activities is complex-commensurate with the diversity of activities that humans pursue, including sleep (8.27). The capacity for speech and adoption of the bipedal posture in human evolution has resulted in patterns of respiratory muscle activation that differ significantly from most other animals. A disproportionate number of respiratory muscles affect the nose, mouth, pharynx, and larynx, reflecting the vital importance of coordinated muscle activity to control upper airway patency during both wakefulness and sleep. The upright posture has freed the hands from locomotor functions, but the evolutionary history and ontogeny of forelimb muscles pervades the patterns of activation and the forces generated by these muscles during breathing. The distinction between respiratory and nonrespiratory muscles is artificial, as many "nonrespiratory" muscles can augment breathing under conditions of high ventilator demand. Understanding the ontogeny, innervation, activation patterns, and functions of respiratory muscles is clinically useful, particularly in sleep medicine. Detailed explorations of how the nervous system controls the multiple muscles required for successful completion of respiratory behaviors will continue to be a fruitful area of investigation. © 2019 American Physiological Society. Compr Physiol 9:1025-1080, 2019.

Compr Physiol|2019 Jun 12

Coker SA, Hurwitz HI, Sharma S, Wang D, Jordaan P, Zarate JP, Lewis LD

2019 Jun 11;doi: 10.1007/s00280-019-03880-9

To evaluate the effect of lapatinib on the QTc interval and ECG parameters in patients with advanced solid tumors.

Cancer Chemother Pharmacol|2019 Jun 11

Hou H, Baek JH, Zhang H, Wood F, Gao Y, Flood AB, Swartz HM, Buehler PW

2019 May 16;:1-11doi: 10.2450/2019.0037-19

The goal of red blood cell transfusion is to improve tissue oxygenation. Assessment of red blood cell quality and individualised therapeutic needs can be optimised using direct oxygen (O) measurements to guide treatment. Electron paramagnetic resonance oximetry is capable of accurate, repeatable and minimally invasive measurements of tissue pO. Here we present preclinical proof-of-concept of the utility of electron paramagnetic resonance oximetry in an experimental setting of acute blood loss, transfusion, and post-transfusion monitoring.

Blood Transfus|2019 May 16

Khayal IS, Zhou W, Skinner J

2017;11(4):342-346

Healthcare delivery systems around the world are in crisis. The need to improve health outcomes while decreasing healthcare costs have led to an imminent call to action to While Bioinformatics and Biomedical Engineering have primarily focused on biological level data and biomedical technology, there is clear evidence of the importance of the delivery of care on patient outcomes. Classic singular decomposition approaches from reductionist science are not capable of explaining complex systems. Approaches and methods from systems science and systems engineering are utilized to structure healthcare delivery system data. Specifically, systems architecture is used to develop a multi-scale and multi-dimensional characterization of the healthcare delivery system, defined here as the Healthcare Delivery System Knowledge Base. This paper is the first to contribute a new method of structuring and visualizing a multi-dimensional and multi-scale healthcare delivery system using systems architecture in order to better understand healthcare delivery.

World Acad Sci Eng Technol|2017

Jacobs BL, Lopa SH, Yabes JG, Nelson JB, Barnato AE, Degenholtz HB

2019 Jun 7;pii: S0090-4295(19)30508-4. doi: 10.1016/j.urology.2019.05.029

To examine the relationship between treatment and subsequent functional status among prostate cancer patients.

Urology|2019 Jun 7

Shaker M, Greenhawt M

2019 Jun 10;doi: 10.1001/jamapediatrics.2019.1533

JAMA Pediatr|2019 Jun 10

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