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Mark Owyong, Gizem Efe, Michael Owyong, Aamna J Abbasi, Vaishnavi Sitarama, Vicki Plaks
There is a growing list of cancer immunotherapeutics approved for use in a population with an increasing number of aged individuals. Cancer immunotherapy (CIT) mediates tumor destruction by activating anti-tumor immune responses that have been silenced through the oncogenic process. However, in an aging individual, immune deregulation is positively correlated with age. In this context, it is vital to examine the age-related changes in the tumor microenvironment (TME) and specifically, those directly affecting critical players to ensure CIT efficacy...
2018: Frontiers in Cell and Developmental Biology
Moomal Tasneem, Carly Mannix, Annette Wong, Jennifer Zhang, Gopala Rangan
The availability of disease-modifying drugs for the management of autosomal dominant polycystic kidney disease (ADPKD) has accelerated the need to accurately predict renal prognosis and/or treatment response in this condition. Arginine vasopressin (AVP) is a critical determinant of postnatal kidney cyst growth in ADPKD. Copeptin (the C-terminal glycoprotein of the precursor AVP peptide) is an accurate surrogate marker of AVP release that is stable and easily measured by immunoassay. Cohort studies show that serum copeptin is correlated with disease severity in ADPKD, and predicts future renal events [decline in renal function and increase in total kidney volume (TKV)]...
March 6, 2018: World Journal of Nephrology
Zainab Altai, Marco Viceconti, Amaka C Offiah, Xinshan Li
Fractures of bone account 25% of all paediatric injuries (Cooper et al. in J Bone Miner Res 19:1976-1981, 2004. ). These can be broadly categorised into accidental or inflicted injuries. The current clinical approach to distinguish between these two is based on the clinician's judgment, which can be subjective. Furthermore, there is a lack of studies on paediatric bone to provide evidence-based information on bone strength, mainly due to the difficulties of obtaining paediatric bone samples...
March 10, 2018: Biomechanics and Modeling in Mechanobiology
Numan Cömert, Oya Carlı, H Benan Dinçtürk
The populations of Eurasian lynx in Anatolia are as fragmented as the European populations. Although the origins of and the connections between the European lynx populations have been elucidated, there have been no genetic studies on the lynx populations in Turkey. The lack of genetic and evolutionary information about lynx in Anatolia, which is considered to be a biodiversity hotspot, makes it difficult to track the migration routes during the Quaternary. In this study, we present the genetic characteristics of two isolated lynx populations in Southwest Taurus Mountains and the Turkish Caucasus as well as two individuals from Erzincan area...
March 8, 2018: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
Nastaran Yaghoobi Ershadi, José Manuel Menéndez, David Jiménez
Intelligent Transportation Systems (ITS) allow us to have high quality traffic information to reduce the risk of potentially critical situations. Conventional image-based traffic detection methods have difficulties acquiring good images due to perspective and background noise, poor lighting and weather conditions. In this paper, we propose a new method to accurately segment and track vehicles. After removing perspective using Modified Inverse Perspective Mapping (MIPM), Hough transform is applied to extract road lines and lanes...
2018: PloS One
Francesco Masia, Iestyn Pope, Peter Watson, Wolfgang Langbein, Paola Borri
Microscopy based high-content and high-throughput analysis of cellular systems plays a central role in drug discovery. However, for contrast and specificity, the majority of assays require a fluorescent readout which always comes with the risk of alteration of the true biological conditions. In this work, we demonstrate a label-free imaging platform which combines chemically-specific hyperspectral coherent anti-Stokes Raman scattering microscopy with sparse sampling and Bessel beam illumination. This enabled us to screen multi-well plates at high speed while retaining the high-content chemical analysis of hyperspectral imaging...
March 5, 2018: Analytical Chemistry
David Porter, Noelle Frey, Patricia A Wood, Yanqiu Weng, Stephan A Grupp
BACKGROUND: Anti-CD19 CAR T cell therapy has demonstrated high response rates in patients with relapsed or refractory (r/r) B cell malignancies but is associated with significant toxicity. Cytokine release syndrome (CRS) is the most significant complication associated with CAR T cell therapy, and it is critical to have a reproducible and easy method to grade CRS after CAR T cell infusions. DISCUSSION: The Common Terminology Criteria for Adverse Events scale is inadequate for grading CRS associated with cellular therapy...
March 2, 2018: Journal of Hematology & Oncology
Maria Dafne Cardamone, Bogdan Tanasa, Carly T Cederquist, Jiawen Huang, Kiana Mahdaviani, Wenbo Li, Michael G Rosenfeld, Marc Liesa, Valentina Perissi
As most of the mitochondrial proteome is encoded in the nucleus, mitochondrial functions critically depend on nuclear gene expression and bidirectional mito-nuclear communication. However, mitochondria-to-nucleus communication pathways in mammals are incompletely understood. Here, we identify G-Protein Pathway Suppressor 2 (GPS2) as a mediator of mitochondrial retrograde signaling and a transcriptional activator of nuclear-encoded mitochondrial genes. GPS2-regulated translocation from mitochondria to nucleus is essential for the transcriptional activation of a nuclear stress response to mitochondrial depolarization and for supporting basal mitochondrial biogenesis in differentiating adipocytes and brown adipose tissue (BAT) from mice...
March 1, 2018: Molecular Cell
Ally Ha, Carly Richards, Erik Criman, Jillian Piaggione, Christopher Yheulon, Robert Lim
BACKGROUND: Surgical energy injuries are an underappreciated phenomenon. Improper use of surgical energy or poor attention to patient safety can result in operating room fires, tissue injuries, and interferences with other electronic devices, while rare complications can be devastatingly severe. Despite this, there is no current standard requirement for educating surgeons on the safe use of energy-based devices or evaluation of electrosurgery (ES) education in residency training, credentialing, or practice...
March 1, 2018: Surgical Endoscopy
Viviana Mucci, Yoon-Hee Cha, Floris L Wuyts, Angelique Van Ombergen
Mal de debarquement syndrome (MdDS) is a neurological condition typically characterized by a sensation of motion, which in most cases manifests after disembarking from a vehicle (e.g., boat, plane, and car). However, the same symptoms can also occur spontaneously. Two main theories of the pathophysiology of MdDS are briefly summarized here. In this perspective, we aimed to report the most recent findings on neuroimaging studies related to MdDS, as well as to suggest further potential research questions that could be addressed with the use of neuroimaging techniques...
2018: Frontiers in Neurology
Jae H Park, F Andres Romero, Ying Taur, Michel Sadelain, Renier J Brentjens, Tobias M Hohl, Susan K Seo
Background: Chimeric antigen receptor (CAR)-modified T cells that target the CD19 antigen present a novel promising therapy for the treatment of relapsed B-cell acute lymphoblastic leukemia (ALL). Although cytokine release syndrome (CRS) and neurotoxicity have emerged as predominant non-infectious complications of CD19 CAR T cell therapy, infections associated with this treatment modality have not been well documented. Methods: We analyzed infectious complications that followed CD19 CAR T cell therapy in 53 adult patients with relapsed ALL enrolled in a phase I clinical trial at Memorial Sloan Kettering Cancer Center (NCT01044069)...
February 22, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Vanessa Ferreira, Ramanakumar V Agnihotram, Andreas Bergdahl, Stefanus J van Rooijen, Rashami Awasthi, Francesco Carli, Celena Scheede-Bergdahl
PURPOSE: Multimodal prehabilitation programs (exercise, nutrition, and anxiety reduction) have been shown to be successful for enhancing patients' physical function prior to surgery, although adherence remains a challenge. Given the short pre-operative period, maintaining adherence is critical to maximize program effectiveness. This study was designed to better understand patients' perspectives of prehabilitation and to identify factors related to program adherence. METHODS: A qualitative descriptive study was conducted based on 52 cancer patients enrolled in a prehabilitation program at the Montreal General Hospital, Montreal, Canada...
February 24, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Carly Leung, Si Hui Tan, Nick Barker
The discovery of leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) as both a marker of adult stem cells and a critical modulator of their activity via its role as an effector of Wnt/R-spondin (Rspo) signaling has driven major advances in our understanding of stem cell biology during homeostasis, regeneration, and disease. Exciting new mouse and organoid culture models developed to study the endogenous behavior of Lgr5-expressing cells in health and disease settings have revealed the existence of facultative stem cell populations responsible for tissue regeneration, cancer stem cells (CSCs) driving metastasis in the gut, and Lgr5+ niche cells in the lung...
February 21, 2018: Trends in Cell Biology
Jayne F Martin Carli, Charles A LeDuc, Yiying Zhang, George Stratigopoulos, Rudolph L Leibel
Genetic variants within the FTO (α-ketoglutarate-dependent dioxygenase) gene have been strongly associated with a modest increase in adiposity as a result of increased food intake. These risk alleles are associated with decreased expression of both FTO and neighboring RPGRIP1L (retinitis pigmentosa GTPase regulator-interacting protein 1 like). RPGRIP1L encodes a protein that is critical to the function of the primary cilium, which conveys extracellular information to the cell. Rpgrip1l+/- mice exhibit increased adiposity, in part, as a result of hyperphagia...
February 21, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Qing-He Tong, Tian-Yang Yan, Tao Tao, Lei Zhang, Li-Qi Xie, Haojie Lu
Due to the critical role glycation plays in many serious pathological conditions, such as diabetes, it is of great significance to discov-er protein glycation at early stage for precaution and prediction of the disease. Here, a method of reductive amination combining dimethylation (RAD) was developed for the quantification of early stage glycated proteins. The quantitative analysis was first car-ried out by reducing the samples using NaBH3CN or NaBD3CN, resulting in 1 Da mass shift and the stabilization of early stage pro-tein glycation...
February 21, 2018: Analytical Chemistry
Jamie E Moscovitz, Amit S Kalgutkar, Kelly Nulick, Nathaniel Johnson, Zhiwu Lin, Theunis C Goosen, Yan Weng
The potential for drug-drug interactions (DDIs) arising from transcriptional regulation of drug disposition genes via activation of nuclear receptors (NRs) such as pregnane X receptor (PXR), constitutive androstane receptor (CAR), and/or aryl hydrocarbon receptor (AhR) remains largely unexplored, as highlighted in a recent guidance document from the European Medicines Agency. The goal of this research was to establish PXR/CAR/AhR-specific drug metabolizing enzyme (DME) and transporter gene expression signatures in sandwich-cultured cryopreserved human hepatocytes using selective activators of PXR (rifampin), CAR (CITCO) and AhR (omeprazole)...
February 12, 2018: Journal of Pharmacology and Experimental Therapeutics
Debra L Madden
PURPOSE OF REVIEW: In 2016, the American Society of Clinical Oncology (ASCO) announced immunotherapy as the year's top cancer advance in its "Clinical Cancer Advances 2016: ASCO's Annual Report on Progress Against Cancer." Further, ASCO again named "Immunotherapy 2.0" as the 2017 advance of the year, emphasizing the recent, rapid pace of research into new agents that harness and enhance the innate abilities of the immune system to recognize and fight cancers-and stressing that such agents have extended the lives of many patients with late-stage cancers for which there have been few treatment options...
February 7, 2018: Current Oncology Reports
Pawel P Posadzki, Ram Bajpai, Bhone Myint Kyaw, Nicola J Roberts, Amnon Brzezinski, George I Christopoulos, Ushashree Divakar, Shweta Bajpai, Michael Soljak, Gerard Dunleavy, Krister Jarbrink, Ei Ei Khaing Nang, Chee Kiong Soh, Josip Car
BACKGROUND: Our aims were to evaluate critically the evidence from systematic reviews as well as narrative reviews of the effects of melatonin (MLT) on health and to identify the potential mechanisms of action involved. METHODS: An umbrella review of the evidence across systematic reviews and narrative reviews of endogenous and exogenous (supplementation) MLT was undertaken. The Oxman checklist for assessing the methodological quality of the included systematic reviews was utilised...
February 5, 2018: BMC Medicine
Takahiro Isshiki, Jacobo Antona-Makoshi, Atsuhiro Konosu, Yukou Takahashi
This study addresses the virtual optimization of the technical specifications for a recently developed Advanced Pedestrian Legform Impactor (aPLI). The aPLI incorporates a number of enhancements for improved lower limb injury predictability with respect to its predecessor, the FlexPLI. It also incorporates an attached Simplified Upper Body Part (SUBP) that enables the impactor's applicability to evaluate pedestrian's lower limb injury risk also with high-bumper cars. The response surface methodology was applied to optimize both the aPLI's lower limb and SUBP specifications, while imposing a total mass upper limit of 25 kg that complies with international standards for maximum weight lifting allowed for a single operator in the laboratory setting...
November 2017: Stapp Car Crash Journal
Daniel A Hashimoto, Guy Rosman, Daniela Rus, Ozanan R Meireles
OBJECTIVE: The aim of this review was to summarize major topics in artificial intelligence (AI), including their applications and limitations in surgery. This paper reviews the key capabilities of AI to help surgeons understand and critically evaluate new AI applications and to contribute to new developments. SUMMARY BACKGROUND DATA: AI is composed of various subfields that each provide potential solutions to clinical problems. Each of the core subfields of AI reviewed in this piece has also been used in other industries such as the autonomous car, social networks, and deep learning computers...
January 31, 2018: Annals of Surgery
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