tbuckley/cabot-search huggingface dataset:
Abstract 17705: Is Apical Hypertrophic Cardiomyopathy Distinctive Disease Entity?: Comparative Study Using Cardiac Magnetic Resonance Imaging
Authors: Hyejin Han, Sang-Chol Lee, Ga Yeon Lee, Mirae Lee, Jae K Oh, Seung Woo Park
Journal: Circulation (2010)

Background: Apical hypertrophic cardiomyopathy (HCM), which is characterized by hypertrophy of the apex of the left ventricle, is very frequently observed in patients from Asian countries and has a...
The use of molecular profiling (MP) beyond standard panels in day-to-day practice: A multi-institutional multinational survey.
Authors: Charlotte Rose Lemech, Joshua Newmark, Hendrik-Tobias Arkenau
Journal: Journal of Clinical Oncology (2013)

e17532 Background: The complexity and associated cost of MP in cancer care is rapidly increasing and there are challenges as to its incorporation and utility in day-to-day oncological practice. Methods: A structured survey was sent to 42 institutions in Europe, USA and Asia-Pacific with well-established experience in basic oncology research and drug development. It aimed to gain insight into the frequency of MP beyond standard testing. The results from an 8 week snap-shot period were collated. Results: 42 medical oncologists, 5 radiation oncologists and 4 haematologists from 31 institutions responded; 41 from academic/teaching hospitals, 7 from the private sector and 3 from general hospitals. 26 respondents indicated that MP beyond standard panels was regularly performed. Testing was covered by public funding (38%), grants (35%) or private insurance/self pay (25%) and was performed for the purpose of research, diagnostics and other reasons (48, 47 &amp; 5%, respectively). Gene analyses included DNA/RNA sequencing alone (11%) or in combination with IHC/FISH (38%), gene expression profiling (19%) and/or proteomics (8%). MP analysis was performed on state-of-the-art sequencing platforms (Sanger in 12%, a combination of Sanger and next generation sequencing (NGS) in 35% and NGS alone in 15%). Archived (60%) and fresh frozen biopsies (40%) were analyzed with a turnaround of &lt;1 week (23%), between 1-3 weeks (66%) and &gt;3 weeks (11%). 66% of results were discussed in a multidisciplinary meeting. Biobanking was available in 48% institutions with bioinformatics support available in 29%. The main challenges identified were funding and associated costs, incorporation of bioinformatics, data quality and staying abreast of new technologies. Conclusions: The use of MP beyond standard panels is increasing in both complexity and availability. Mastering clinical accessibility, data volume, and technical innovation will be key to incorporate MP in day–to-day practice.
SWOG 0722: A phase II study of mTOR inhibitor everolimus (RAD001) in malignant pleural mesothelioma (MPM).
Authors: Linda L. Garland, Sai-Hong Ou, James Moon, Philip C Mack, Joseph Testa, Anne S. Tsao, Antoinette J. Wozniak, David R. Gandara
Journal: Journal of Clinical Oncology (2012)

7083 Background: MPM preclinical studies demonstrate activation of AKT pathway proteins, including mTOR, and provide the rationale to test everolimus, an mTOR inhibitor, in MPM. Methods: Unresectable MPM patients (pts) after 1-2 systemic regimens (including a platinum-based regimen), with PS 0-1, measurable disease and adequate organ function were treated with daily oral everolimus 10 mg. Study endpoints were progression-free survival (PFS) at 4 months, response rate,overall survival (OS), and frequency/severity of toxicities. Results: 61 pts were registered between 12/2008 and 9/2011; there were 57 evaluable pts for the primary endpoint of 4-month PFS. Median age was 65.9 yrs; M/F 43/14; prior regimens (1/2: 58%/42%); PS 0/1 (21%/79%); epithelial subtype 61%; biphasic 7%; NOS 28%; pending 4%. 5 pts remain on treatment. Preliminary data for 35 of 57 pts are as follows: RR 0% by standard RECIST and DCR of 14/35 (40%); data by mod RECIST are not yet available. Estimated 4-month PFS was 34% with an estimated median PFS of 3 months. The null hypothesis of 4-month PFS = 30% could not be rejected (p=0.28). 41 pts have died; median OS is estimated at 5 months. Frequent grade 1-3 toxicities were fatigue (55.4%), hypertriglyceridemia (41.1%), anemia (39.3%), nausea (33.9%), oral mucositis (32.1%), anorexia (32.1%), diarrhea (26.8%), and hyperglycemia (26.8%). One pt each had grade 4 and grade 5 dyspnea. Conclusions: The trial did not achieve the primary endpoint of an improvement of PFS at 4 months from 30% to 50%. Inhibition of mTOR using single agent everolimus is not active in unselected MPM patients. Other strategies for targeting the activated AKT pathway in MPM remain of interest.
Lipid oversupply induces CD36 sarcolemmal translocation via dual modulation of PKCζ and TBC1D1: an early event prior to insulin resistance
Authors: Bili Zhu, Ming-Yue Li, Quanming Lin, Zhicheng Liang, Qihang Xin, Menghuan Wang, Zhendan He, Xiaomei Wang, Xuli Wu, George G. Chen, Peter CY Tong, Weizhen Zhang, Li-Zhong Liu
Journal: Theranostics (2020)

Lipid oversupply may induce CD36 sarcolemmal translocation to facilitate fatty acid transport, which in turn causes dyslipidemia and type 2 diabetes. However, the underlying mechanisms of CD36 redistribution are still yet to be unraveled. Methods: High fat diet fed mice and palmitate/oleic acid-treated L6 cells were used to investigate the initial events of subcellular CD36 recycling prior to insulin resistance. The regulation of CD36 sarcolemmal translocation by lipid oversupply was assessed by insulin tolerance test (ITT), oral glucose tolerance test (OGTT), glucose/fatty acid uptake assay, surface CD36 and GLUT4 detection, and ELISA assays. To elucidate the underlying mechanisms, specific gene knockout, gene overexpression and/or gene inhibition were employed, followed by Western blot, co-immunoprecipitation, immunostaining, and kinase activity assay. Results: Upon lipid/fatty acid overload, PKCζ activity and TBC1D1 phosphorylation were enhanced along with increased sarcolemmal CD36. The inhibition of PKCζ or TBC1D1 was shown to block fatty acid-induced CD36 translocation and was synergistic in impairing CD36 redistribution. Mechanically, we revealed that AMPK was located upstream of PKCζ to control its activity whereas Rac1 facilitated PKCζ translocation to the dorsal surface of the cell to cause actin remodeling. Furthermore, AMPK phosphorylated TBC1D1 to release retained cytosolic CD36. The activated PKCζ and phosphorylated TBC1D1 resulted in a positive feedback regulation of CD36 sarcolemmal translocation. Conclusion: Collectively, our study demonstrated exclusively that lipid oversupply induced CD36 sarcolemmal translocation via dual modulation of PKCζ and TBC1D1, which was as an early event prior to insulin resistance. The acquired data may provide potential therapy targets to prevent lipid oversupply-induced insulin resistance.
CircPCMTD1: A Protein-Coding Circular RNA That Regulates DNA Synthesis in Leukemic Myeloblasts
Authors: Dimitrios Papaioannou, Remi Buisson, Andreas Petri, Allison Walker, Marius Bill, Felice Pepe, Deedra Nicolet, Lauren A Woodward, Krzysztof Mrózek, Malith Karunasiri, Gregory K. Behbehani, Emanuele Cocucci, Guramrit Singh, Sakari Kauppinen, Adrienne M. Dorrance, Clara D. Bloomfield, Ramiro Garzon
Journal: Blood (2019)
SURG-14. DOES WAITING MATTER? HOW TIME FROM DIAGNOSTIC MRI TO SURGICAL RESECTION AFFECTS OUTCOMES IN NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Jacob Young, Rachel Muster, Ankush Chandra, Ramin Morshed, Manish Aghi
Journal: Neuro-Oncology (2019)

Abstract Surgical resection is standard of care for patients with lesions concerning for high-grade glioma on MRI scan. There is no consensus on the urgency of the procedure for patients with good clinical performance status. Treatment history and functional outcomes were collected retrospectively from the electronic medical record for 105 consecutive patients with newly diagnosed WHO Grade IV gliomas who underwent surgical resection at the University of California, San Francisco in 2014 and 2015 (41% female, average age = 61.25). Median preoperative KPS score was 80. Median wait time to surgery was 11 days after the initial MRI scan (range: 0–213 days). Mean tumor volume at the time of initial MRI scan was 29.0 cm3 (SD = 26.1 cm3), which did not significantly differ from the mean pre-operative tumor volume of 31.2 cm3 (SD = 27.3 cm3). In this retrospective cohort, patients with larger glioblastomas were taken to surgery more quickly. Patients who presented to the emergency room were more likely to wait less than 7 days (p &amp;lt; 0.001). Patients who waited less than 7 days had a larger initial and pre-operative tumor volume compared to patients who waited between 7–21 days and patients who waited over 21 days (p=&amp;lt; 0.001, p=&amp;lt; 0.001). Tumor growth occurred in 10% of patients who waited one week or less, 26% of patients who waited one to three weeks, and 55% of patients who waited over 3 weeks. Overall survival was not significantly affected by wait time until tumor resection (p=0.52). Additionally, Tumor growth was not associated with postoperative outcomes including postoperative KPS score, postoperative deficits, 3-month follow up KPS score, overall survival, and survival after surgery. In conclusion, longer wait time to surgery does not impact overall survival, pre-, and post-operative KPS, but the tumor is likely to grow in the interim.
British Association of Dermatologists centenary year: standing on the shoulders of giants
Authors: J.R. Ingram, D. J. Gawkrodger
Journal: British Journal of Dermatology (2020)

E‐mail: IngramJR@cardiff.ac.uk Conflicts of interest: J.R.I. is Editor of the British Journal of Dermatology. D.J.G. is honorary treasurer and a trustee of the British Skin Foundation. In 2020, the British Association of Dermatologists (BAD) marks its one hundredth year since inception. One of its founding principles is to foster research to improve the care of those with skin disease. It does this in several ways including financial support for the British Skin Foundation, which makes grants available for dermatology research, and via its journals, the BJD and Clinical and Experimental Dermatology (CED). As part of the centenary celebrations a look back at some of the best papers in the BJD and CED is warranted. There are some real gems, including landmark publications introducing Sweet syndrome, orf, Lyell syndrome (toxic epidermal necrolysis, TEN), Ludwig's classification of androgenetic alopecia and the Dermatology Life Quality Index (DLQI). Let's start from the 1920s and work forwards to the present day. The paper by Cranston Low published in the October 1928 issue of The British Journal of Dermatology and Syphilis (subsequently renamed the BJD), highlights the ‘eczema–asthma–prurigo–complex’.1 It provides an early description of atopy, which in the 1920s was not well recognized, a situation that is difficult to contemplate now.
A review of different ways to assess rosacea
Authors: J.G.M. Logger, F.M.C. de Vries, P.E J. van Erp, E.M.G.J. de Jong, M. Peppelman, R.J.B. Driessen
Journal: British Journal of Dermatology (2020)

Rosacea is a troublesome adult skin problem causing redness, lumps and pimples, mainly on the face. One of the causes is a tiny mite called demodex. Rosacea is commoner in women and usually improves with antibiotics but can be very persistent. In order to find better treatments, researchers need a reliable way to measure the severity of a person's condition, and its response to therapy. This is difficult because rosacea looks and behaves differently in different people and there are many ways to describe the appearance. This team from Holland searched the medical literature to see what investigations have been used. They examined 78 published studies which assessed skin appearance and function non‐invasively (without disrupting the skin). It was difficult to compare the results because researchers expressed them in a variety of ways. There were weaknesses in the design and reporting of experiments as well as inconsistencies in the findings. Many techniques and devices have been used: microscopes and dermatoscopes to magnify skin blood vessels and other features; computer programmes to analyse skin colour; ultrasound to examine skin irregularities; electrical recording of skin water content; measurement of surface oils and acidity; laser assessment of skin blood flow; various devices to measure temperature. Some of these techniques would only be used in research but others, such as dermoscopy, could be used in the clinic. Several of these measurements showed no clear relationship to rosacea severity. The most promising techniques included a surface microscope to count demodex mites and techniques for measuring skin redness, water content and water loss. This summary relates to the study: Noninvasive objective skin measurement methods for rosacea assessment: a systematic review
Inhibition of Haspin Kinase Promotes Cell-Intrinsic and Extrinsic Antitumor Activity
Authors: Johannes C. Melms, Sreeram Vallabhaneni, Caitlin E. Mills, Clarence Yapp, Jia-Yun Chen, Eugenio Morelli, Patricia Waszyk, Sushil Kumar, Derrick Deming, Nienke Moret, Steven Rodriguez, Kartik Subramanian, Meri Rogava, Adam N.R. Cartwright, Adrienne Luoma, Shaolin Mei, Titus J. Brinker, David M. Miller, Alexander Spektor, Dirk Schadendorf, Nicolo Riggi, Kai W. Wucherpfennig, Peter K. Sorger, Benjamin Izar
Journal: Cancer Research (2019)

Patients with melanoma resistant to RAF/MEK inhibitors (RMi) are frequently resistant to other therapies, such as immune checkpoint inhibitors (ICI), and individuals succumb to their disease. New drugs that control tumor growth and favorably modulate the immune environment are therefore needed. We report that the small-molecule CX-6258 has potent activity against both RMi-sensitive (RMS) and -resistant (RMR) melanoma cell lines. Haspin kinase (HASPIN) was identified as a target of CX-6258. HASPIN inhibition resulted in reduced proliferation, frequent formation of micronuclei, recruitment of cGAS, and activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. In murine models, CX-6258 induced a potent cGAS-dependent type-I IFN response in tumor cells, increased IFNγ-producing CD8+ T cells, and reduced Treg frequency in vivo. HASPIN was more strongly expressed in malignant compared with healthy tissue and its inhibition by CX-6258 had minimal toxicity in ex vivo-expanded human tumor-infiltrating lymphocytes (TIL), proliferating TILs, and in vitro differentiated neurons, suggesting a potential therapeutic index for anticancer therapy. Furthermore, the activity of CX-6258 was validated in several Ewing sarcoma and multiple myeloma cell lines. Thus, HASPIN inhibition may overcome drug resistance in melanoma, modulate the immune environment, and target a vulnerability in different cancer lineages. SIGNIFICANCE: HASPIN inhibition by CX-6258 is a novel and potent strategy for RAF/MEK inhibitor-resistant melanoma and potentially other tumor types. HASPIN inhibition has direct antitumor activity and induces a favorable immune microenvironment.
Lipoprotein(a) Reduction in Persons with Cardiovascular Disease
Authors: Sotirios Tsimikas, Ewa Karwatowska-Prokopczuk, Ioanna Gouni-Berthold, Jean-Claude Tardif, Seth J. Baum, Elizabeth Steinhagen-Thiessen, Michael D. Shapiro, Erik S. Stroes, Patrick M. Moriarty, Børge G. Nordestgaard, Shuting Xia, Jonathan Guerriero, Nicholas J. Viney, Louis O’Dea, Joseph L. Witztum
Journal: New England Journal of Medicine (2020)

Lipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis. There are no approved pharmacologic therapies to lower lipoprotein(a) levels.We conducted a randomized, double-blind, placebo-controlled, dose-ranging trial involving 286 patients with established cardiovascular disease and screening lipoprotein(a) levels of at least 60 mg per deciliter (150 nmol per liter). Patients received the hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-LRx, referred to here as APO(a)-LRx (20, 40, or 60 mg every 4 weeks; 20 mg every 2 weeks; or 20 mg every week), or saline placebo subcutaneously for 6 to 12 months. The lipoprotein(a) level was measured with an isoform-independent assay. The primary end point was the percent change in lipoprotein(a) level from baseline to month 6 of exposure (week 25 in the groups that received monthly doses and week 27 in the groups that received more frequent doses).The median baseline lipoprotein(a) levels in the six groups ranged from 204.5 to 246.6 nmol per liter. Administration of APO(a)-LRx resulted in dose-dependent decreases in lipoprotein(a) levels, with mean percent decreases of 35% at a dose of 20 mg every 4 weeks, 56% at 40 mg every 4 weeks, 58% at 20 mg every 2 weeks, 72% at 60 mg every 4 weeks, and 80% at 20 mg every week, as compared with 6% with placebo (P values for the comparison with placebo ranged from 0.003 to <0.001). There were no significant differences between any APO(a)-LRx dose and placebo with respect to platelet counts, liver and renal measures, or influenza-like symptoms. The most common adverse events were injection-site reactions.APO(a)-LRx reduced lipoprotein(a) levels in a dose-dependent manner in patients who had elevated lipoprotein(a) levels and established cardiovascular disease. (Funded by Akcea Therapeutics; ClinicalTrials.gov number, NCT03070782.).
Clinical next generation sequencing (NGS) of fine needle aspiration (FNA) biopsies in non-small cell lung (NSCLC) and pancreatic cancers.
Authors: Matthew J. Hawryluk, Jeffrey S. Ross, Christine E. Sheehan, Jie He, Geneva Young, Geoff Otto, Roman Yelensky, Doron Lipson, Gary A. Palmer, Phil Stephens, Vincent A. Miller
Journal: Journal of Clinical Oncology (2013)

11100 Background: FNA is a common diagnostic procedure for the evaluation of pulmonary and pancreatic masses. We sought to determine whether NGS could be performed on these small specimens and to characterize heterogeneity across classes of genomic alterations (GA) in a subset of paired FNA and matched resected primary tumors. Methods: DNA was isolated from formalin fixed paraffin embedded (FFPE) sections of FNA cell blocks using 40µm total sections for NSCLC and 20µm total sections for pancreatic cancers in a CLIA-certified lab (Foundation Medicine). DNA sequencing was performed for 3,320 exons of 182 cancer-related genes and 37 introns of 14 genes frequently rearranged in cancer on indexed, adaptor ligated, hybridization-captured libraries to a median depth of 931x for the NSCLC and 416x for the pancreatic FNAs. Results: Genomic profiles were successfully generated from 19/19 of the NSCLC and 22/23 of the pancreatic FNA cases. We found 97 GA in the 19 NSCLC FNAs (range 2-9, average 5.1 GA per patient). 68% of the patients had GA in TP53 and 21% in KRAS. Only 16% (3/19) patients did not exhibit an actionable alteration. We found 99 GA in the 23 pancreatic cancer FNAs (range 0-12, average 4.3 per patient). 74% of the patients had GA in KRAS. There was 94% concordance of GA found in 4 matched FNA and primary tumor pairs for the pancreatic cases. For the single discordance, manual inspection of the reads of the discordant allele indicated evidence of loss of heterozygosity. Conclusions: NGS can be reliably performed on small FNA samples processed into cell blocks, and the GA discovered significantly correlates with the GA found in matched primary tumors. This study demonstrates the feasibility of NGS in analyzing FNA samples and further broadens the spectrum of commonly encountered specimen types to which this approach can be successfully applied.
Molecular imaging biomarkers for immune checkpoint inhibitor therapy
Authors: Pim P van de Donk, Laura Kist de Ruijter, Marjolijn N Lub-de Hooge, Adrienne H Brouwers, Anthonie J van der Wekken, Sjoukje F Oosting, Rudolf SN Fehrmann, Derk Jan A de Groot, Elisabeth GE de Vries
Journal: Theranostics (2020)

Immune checkpoint inhibitors (ICIs) have substantially changed the field of oncology over the past few years. ICIs offer an alternative treatment strategy by exploiting the patients' immune system, resulting in a T cell mediated anti-tumor response. These therapies are effective in multiple different tumor types. Unfortunately, a substantial group of patients do not respond to ICIs. Molecular imaging, using single-photon emission computed tomography (SPECT) and positron emission tomography (PET), can provide non-invasive whole-body visualization of tumor and immune cell characteristics and might support patient selection or response evaluations for ICI therapies. In this review, recent studies with
Screening for Chlamydia trachomatis in subfertile women
Authors: S Macmillan, A Templeton
Journal: Human Reproduction Update (1999)

for infertility investigation and treatment. We also studied the the prevalence of chlamydial infection in the subfertile are few and conflicting. In this study, more than 400 consecutive effect of age and diagnostic test on prevalence. women presenting for infertility investigation and treatment at a single regional fertility centre were screened for Chlamydia. Half were screened using enzyme immunoassay Materials and methods (EIA) and half by ligase chain reaction (LCR). Prevalence All screening was undertaken in the Aberdeen Fertility Centre, by diagnostic test was 0% with EIA and 1.9% with LCR. comprising a Fertility Clinic (FC) and Assisted Reproduction Unit Overall, the low prevalence was at least partly explained (ARU). Consecutive women were invited to participate in the study by older age. Until more evidence comes from studies by means of an information sheet. The only exclusion criterion was testing consecutive subfertile patients both with EIA and antibiotic use in the past 4 weeks. Participants volunteered by a DNA amplification method such as LCR, centres using giving verbal consent. Approval was received from the local Ethical Committee prior to commencement of the study. EIA should consider using prophylactic antibiotics prior
MicroRNA-204-5p is a tumor suppressor and potential therapeutic target in head and neck squamous cell carcinoma
Authors: Zehang Zhuang, Pei Yu, Nan Xie, Yue Wu, Haichao Liu, Ming Zhang, Yifan Tao, Weiwang Wang, Hanqi Yin, Bin Zou, Jinsong Hou, Xiqiang Liu, Jiong Li, Hongzhang Huang, Cheng Wang
Journal: Theranostics (2020)

Elucidation of the molecular mechanisms governing aggressiveness of HNSCC may provide clinical therapeutic strategies for patients. In this study, a novel hub miR-204-5p functioning as tumor suppressor has been identified and explored in HNSCC. Methods: A novel hub miR-204-5p was identified based on miRNA microarray, bioinformatics analysis and validated in different HNSCC patient cohorts. The functional role of miR-204-5p and its downstream and upstream regulatory machinery were investigated by gain-of-function and loss-of-function assays in vitro and in vivo. Interactions among miR-204-5p and SNAI2/SUZ12/HDAC1/STAT3 complex were examined by a series of molecular biology experiments. Then, the clinical relevance of miR-204-5p and its targets were evaluated in HNSCC samples. HNSCC patient-derived xenograft (PDX) model was used to assess the therapeutic value of miR-204-5p. Results: We reveal that miR-204-5p as a tumor suppressor is commonly repressed in HNSCC, which can inhibit tumor growth, metastasis and stemness. Mechanically, miR-204-5p suppresses epithelial-mesenchymal transition (EMT) and STAT3 signaling by targeting SNAI2, SUZ12, HDAC1 and JAK2. Among these targets, we further showed that SNAI2, SUZ12, and HDAC1 form a repressive complex on CDH1 promoter to maintain EMT in HNSCC. In turn, the SNAI2/SUZ12/HDAC1 complex interacts with STAT3 on miR-204-5p-regulatory regions to suppress the transcription of miR-204-5p. Moreover, we also show that decrease of miR-204-5p indicates a poor prognosis in HNSCC patients and administration of agomiR-204-5p inhibits tumor growth and metastasis in HNSCC PDX models. Conclusion: miR-204-5p-SNAI2/SUZ12/HDAC1/STAT3 regulatory circuit has a critical role in maintaining aggressiveness of HNSCC, suggesting that miR-204-5p might serve as a promising therapeutic target for clinical intervention.