tbuckley/cabot-search huggingface dataset:
Potential Cause of Nodding Syndrome Identified
Authors: M.J. Friedrich
Journal: JAMA (2017)

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Childhood adversity and risk of suicide: cohort study of 548 721 adolescents and young adults in Sweden
Authors: Charlotte Björkenstam, Kyriaki Kosidou, Emma Björkenstam
Journal: BMJ (2017)

Objective To examine the relation between childhood adversity, the role of school performance, and childhood psychopathology and the risk of suicide.Design Cohort study of register based indicators of childhood adversity (at ages 0-14) including death in the family (suicide analysed separately), parental substance abuse, parental psychiatric disorder, substantial parental criminality, parental separation/single parent household, receipt of public assistance, and residential instability.Setting Swedish medical birth register and various Swedish population based registers.Participants 548 721 individuals born 1987-91.Main outcome measures Estimates of suicide risk at ages 15-24 calculated as incidence rate ratios adjusted for time at risk and confounders.Results Adjusted incidence rate ratios for the relation between childhood adversity and suicide during adolescence and young adulthood ranged from 1.6 (95% confidence interval 1.1 to 2.4) for residential instability to 2.9 (1.4 to 5.9) for suicide in the family. There was a dose-response relation between accumulating childhood adversity and risk: 1.1 (0.9 to 1.4) for those exposed to one adversity and 1.9 (1.4 to 2.5) and 2.6 (1.9 to 3.4) for those exposed to two and three or more adversities, respectively. The association with increased risk of suicide remained even after adjustment for school performance and childhood psychopathology.Conclusion Childhood adversity is a risk factor for suicide in adolescence and young adulthood, particularly accumulated adversity. These results emphasise the importance of understanding the social mechanisms of suicide and the need for effective interventions early in life, aiming to alleviate the risk in disadvantaged children.
P95HER2 as a predictive marker in the phase III randomized HERNATA trial of trastuzumab and chemotherapy as first-line therapy to metastatic or locally advanced HER2-positive breast cancer.
Authors: Ann S. Knoop, Michael Andersson, Karsten D. Bjerre, Yi Zang, Catherine A. Schnabel, Anne-Vibeke Laenkholm
Journal: Journal of Clinical Oncology (2015)

559 Background: HER2+ tumours express a series of carboxy-terminal HER2 fragments (CTFs or p95HER2) lacking the receptor extracellular domain that have been investigated as a potential trastuzumab resistance marker. Utilizing patients with locally-advanced or metastatic HER2+ breast cancer enrolled in the randomized HERNATA study, we assessed the expression of p95HER2 and its association with time to progression (TTP). Methods: Immunohistochemical (IHC) staining for p95HER2 was performed using a monoclonal antibody that specifically recognizes 611-CTF variant, blinded to clinical outcome (bioTheranostics Inc.). All slides were scored in consensus with a pre-defined cut-point (10% cells of strong staining) to define positive P95HER status. Additionally, an H-score (0-300) based on IHC staining was calculated with a preselected cut-point, that ensured 30% of the patient to be classified p95HER2 positive. TTP was analysed by Cox proportional hazards models. The model assumption of proportional hazards was investigated by Schoenfeld residuals and was used to evaluate if re-parameterization of p95HER2 by time-dependent variables (cut-point: 1.5 year after randomization) affects the association of p95HER2 status with TTP. Results: P95HER2 staining was available from 207 (73%) patients within the HERNATA intention to treat population of 284 patients. 36% of the patients were p95HER2 positive ( ≥ 10 % strong staining). Kaplan-Meier analysis showed no significant association between p95HER2 status and TTP (p = 0.68). However, Cox unadjusted analysis showed a marginally significant association between p95HER2 status and TTP 1.5 year after randomization (P = 0.04; HR 0-1.5 year after randomization: 1.04, 95% CI: 0.74-1.46; HR > 1.5-year after randomization: 2.60, 95% CI: 1.23-5.51) – which were confirmed in the adjusted analyses, as seen by similar HR estimates although not significant (P = 0.07). Results based on H-score are similar. Conclusions: No evidence of p95HER2 as a resistance biomarker for trastuzumab was found in this cohort of HER2+ metastatic breast cancer patients from the randomized HERNATA trial.
Clinical significance of somatic mutation in unexplained blood cytopenia
Authors: Luca Malcovati, Anna Gallì, Erica Travaglino, Ilaria Ambaglio, Ettore Rizzo, Elisabetta Molteni, Chiara Elena, Virginia Valeria Ferretti, Silvia Catricalà, Elisa Bono, Gabriele Todisco, Antonio Bianchessi, Elisa Rumi, Silvia Zibellini, Daniela Pietra, Emanuela Boveri, Clara Camaschella, Daniela Toniolo, Elli Papaemmanuil, Seishi Ogawa, Mario Cazzola
Journal: Blood (2017)
Antiviral response and resistance surveillance for HBeAgnegative patients enrolled in a combination study evaluatingemtricitabine plus clevudine versus emtricitabine monotherapyfor the treatment of chronic hepatitis B infection.
Authors: Andi Snow, Zahary Krastev, Seng Gee Lim, Tay Meng Ng, Iskren Andreev Kotzen, Sing Chan, Petr Husa, Jan Šperl, Herve Mommeja-Marin, Katyna Borroto-Esoda, Jane Anderson, Elsa Mondou, Jeff Sorbel, Franck Rousseau
Journal: Hepatology (2005)
Addition of Hsp27 inhibitor apatorsen to first-line gemcitabine/carboplatin in advanced squamous cell lung cancer: design of the Cedar (TM) trial
Authors: P Schmid, D Muthukumar, Fiona H Blackhall, J Lester, S Khan, M Illsley, J Adams, S Baijal, A Garcia, C Smith, S Lee, C Jacobs, G Middleton, C James, K Mousa, S Sarker, L Lim
Journal: Journal of Thoracic Oncology (2015)
Targeting MDS and AML Stem Cells with AZD-9150 Mediated Inhibition of STAT3
Authors: Aditi Shastri, Margarida Teixeira, Sanchari Bhattacharyya, Nandini Ramachandra, Robert Lopez, Goutham Ravipati, Jonathan Feld, Yosman Dhar, Tushar Damodar Bhagat, Gaurav Choudhary, Orsolya Giricz, Matthias Bartenstein, Ashwin Sridharan, Shanisha Gordon-Mitchell, George Nawanko, Kith Pradhan, Amal Ahmed, Keshav Raghavendran, Rubashruti Kanna, Hina Khan, Ioannis Mantzaris, Andrea Pellagatti, Jacqueline Boultwood, Youngsoo Kim, Robert McLeod, Richard Woessner, Ulrich Steidl, Britta Will, Amit Verma
Journal: Blood (2016)
Regulatory Aspects of Optical Methods and Exogenous Targets for Cancer Detection
Authors: Willemieke S. Tummers, Jason M. Warram, Kiranya E. Tipirneni, John Fengler, Paula Jacobs, Lalitha Shankar, Lori Henderson, Betsy Ballard, T. Joshua Pfefer, Brian W. Pogue, Jamey P. Weichert, Michael Bouvet, Jonathan Sorger, Christopher H. Contag, John V. Frangioni, Michael F. Tweedle, James P. Basilion, Sanjiv S. Gambhir, Eben L. Rosenthal
Journal: Cancer Research (2017)

Abstract Considerable advances in cancer-specific optical imaging have improved the precision of tumor resection. In comparison to traditional imaging modalities, this technology is unique in its ability to provide real-time feedback to the operating surgeon. Given the significant clinical implications of optical imaging, there is an urgent need to standardize surgical navigation tools and contrast agents to facilitate swift regulatory approval. Because fluorescence-enhanced surgery requires a combination of both device and drug, each may be developed in conjunction, or separately, which are important considerations in the approval process. This report is the result of a one-day meeting held on May 4, 2016 with officials from the National Cancer Institute, the FDA, members of the American Society of Image-Guided Surgery, and members of the World Molecular Imaging Society, which discussed consensus methods for FDA-directed human testing and approval of investigational optical imaging devices as well as contrast agents for surgical applications. The goal of this workshop was to discuss FDA approval requirements and the expectations for approval of these novel drugs and devices, packaged separately or in combination, within the context of optical surgical navigation. In addition, the workshop acted to provide clarity to the research community on data collection and trial design. Reported here are the specific discussion items and recommendations from this critical and timely meeting. Cancer Res; 77(9); 2197–206. ©2017 AACR.
TCTAP A-039 Safety and Efficacy of Sirolimus Coated Balloon for the Treatment Coronary In-stent Restenosis: Results from Real World Multicenter Study
Authors: Sameer Dani, Keyur Parikh, Ranjan Shetty, N Prathap Kumar, Jagdish Hiremath
Journal: Journal of the American College of Cardiology (2017)
Micro RNA-3662 Located within the Major Hematopoietic Differentiation Quantitative Trait Locus on Chromosome 6q23 Acts As a Tumor Suppressor By Direct Targeting of the NF-ĸB Transcriptional Activation Pathway
Authors: Sophia E. Maharry, Sujay Mehta, Sandya Liyanarachchi, Christopher J. Walker, Clara D. Bloomfield, Albert de la Chapelle, Ann-Kathrin Eisfeld
Journal: Blood (2014)
Targeting Autocrine CCL5–CCR5 Axis Reprograms Immunosuppressive Myeloid Cells and Reinvigorates Antitumor Immunity
Authors: Yi Ban, Junhua Mai, Xin Li, Marisa Mitchell-Flack, Tuo Zhang, Lixing Zhang, Lotfi Chouchane, Mauro Ferrari, Haifa Shen, Xiaojing Ma
Journal: Cancer Research (2017)

Abstract The tumor-promoting potential of CCL5 has been proposed but remains poorly understood. We demonstrate here that an autocrine CCL5–CCR5 axis is a major regulator of immunosuppressive myeloid cells (IMC) of both monocytic and granulocytic lineages. The absence of the autocrine CCL5 abrogated the generation of granulocytic myeloid-derived suppressor cells and tumor-associated macrophages. In parallel, enhanced maturation of intratumoral neutrophils and macrophages occurred in spite of tumor-derived CCL5. The refractory nature of ccl5-null myeloid precursors to tumor-derived CCL5 was attributable to their persistent lack of membrane-bound CCR5. The changes in the ccl5-null myeloid compartment subsequently resulted in increased tumor-infiltrating cytotoxic CD8+ T cells and decreased regulatory T cells in tumor-draining lymph nodes. An analysis of human triple-negative breast cancer specimens demonstrated an inverse correlation between "immune CCR5" levels and the maturation status of tumor-infiltrating neutrophils as well as 5-year-survival rates. Targeting the host CCL5 in bone marrow via nanoparticle-delivered expression silencing, in combination with the CCR5 inhibitor Maraviroc, resulted in strong reductions of IMC and robust antitumor immunities. Our study suggests that the myeloid CCL5–CCR5 axis is an excellent target for cancer immunotherapy. Cancer Res; 77(11); 2857–68. ©2017 AACR.
Tumor-penetrating peptide enhances transcytosis of silicasome-based chemotherapy for pancreatic cancer
Authors: Xiangsheng Liu, Paulina Lin, Ian Perrett, Joshua Lin, Yu-Pei Liao, Chong Hyun Chang, Jinhong Jiang, Nanping Wu, Timothy Donahue, Zev Wainberg, Andre E. Nel, Huan Meng
Journal: Journal of Clinical Investigation (2017)

Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal; however, some improvement in overall survival has been achieved with the introduction of nanocarriers that deliver irinotecan or paclitaxel. Although it is generally assumed that nanocarriers rely principally on abnormal leaky vasculature for tumor access, a transcytosis transport pathway that is regulated by neuropilin-1 (NRP-1) has recently been reported. NRP-1-mediated transport can be triggered by the cyclic tumor-penetrating peptide iRGD. In a KRAS-induced orthotopic PDAC model, coadministration of iRGD enhanced the uptake of an irinotecan-loaded silicasome carrier that comprises lipid bilayer-coated mesoporous silica nanoparticles (MSNPs); this uptake resulted in enhanced survival and markedly reduced metastasis. Further, ultrastructural imaging of the treated tumors revealed that iRGD coadministration induced a vesicular transport pathway that carried Au-labeled silicacomes from the blood vessel lumen to a perinuclear site within cancer cells. iRGD-mediated enhancement of silicasome uptake was also observed in patient-derived xenografts, commensurate with the level of NRP-1 expression on tumor blood vessels. These results demonstrate that iRGD enhances the efficacy of irinotecan-loaded silicasome-based therapy and may be a suitable adjuvant in nanoparticle-based treatments for PDAC.
Late 124I PET/CT Uptake Measurement—Assessment of Appropriate Examination Protocol in Benign Thyroid Diseases
Authors: Martin Freesmeyer, Anja S. Gabler, Christian Kühnel, Thomas Winkens
Journal: Clinical Nuclear Medicine (2017)

Purpose This study aimed at investigating the performance of late 124I PET/CT for radioiodine uptake (RAIU) measurement at 336 hours after administration in patients with benign thyroid diseases requiring radioiodine therapy. Special attention was paid to the comparability of 124I uptake (124I-RAIU) to the clinical standard (131I-RAIU, probe measurement). Considering cost aspects, we sought to establish an economically reasonable examination protocol based on scan duration and administered activity. Methods List-mode PET data sets of 40-minute acquisition time were acquired 336 hours after administration of 1 MBq 124I in 18 patients. Different scan durations were simulated by different reconstruction intervals (RIs) ranging from 5 seconds to 40 minutes, and total thyroid activity was measured. Mean 124I-RAIU levels of each RI were compared with mean 131I-RAIU levels (3 MBq). A hypothetical scan duration or hypothetical activity, respectively, was sought by means of a proportion equation, considering that the length of an RI is equitable to a hypothetical activity. Results After 336 hours, the mean total thyroid activity was 254 ± 7.7 kBq for 131I and 26.9 ± 8.7 kBq for 124I. The mean 124I-RAIU and 131I-RAIU showed high levels of agreement for RI from 2 minutes to 40 minutes. Reconstruction interval shorter than 2 minutes did not result in sufficient agreement. Conclusions The present study confirmed the feasibility of late 124I PET/CT as alternative method for RAIU measurement in patients with benign thyroid diseases; 1 MBq 124I PET/CT scans as short as 2 minutes resulted in RAIU levels comparable to those of standard 131I-RAIU. The parameter “appropriate scan-duration activity product” is proposed to enable an economically reasonable examination protocol.
IGF-1R as a target in head and neck cancer, lung cancer, and cervical cancer: Expression in patient samples and in vitro inhibition studies.
Authors: Tanguy Seiwert, Leo Faoro, Vidya Nallasura, Wasim Naqshbandi, Maria Tretiakova, Mark Lingen, Aliya Husain, Ravi Salgia
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

1527 

Background: IGF-1R is a receptor tyrosine kinase that has emerged recently as a novel therapeutic target. The purpose of this study was to compare IGF-1R expression in head and neck cancer, lung cancer, and cervical cancer and validate its usefulness as a therapeutic target using in-vitro inhibition studies, by itself, in combination with cisplatin chemotherapy, and radiation.    Methods: Tumor tissue microarrays from patients with head and neck cancer, lung cancer (squamous, adeno, large cell, and small cell (one array each) were stained by immunohistochemistry for IGF-1R. Tumor cell lines were treated with a small molecule IGF-1R inhibitor alone, and in combination with cisplatin or radiation and viability was analyzed using either soft agar or media colony formation assays.    Results: Strong expression of IGF-1R was seen in all tumor types including small cell lung cancer in more than 50% of tumors. Inhibition in multiple tumor cell lines lead to growth inhibition/ decrease in colony formation. At least additive effects were identified with both cisplatin and radiation in multiple cell lines.    Conclusion: Our results validate IGF-1R as a therapeutic target in multiple tumors and clinical studies in these tumors are indicated alone or in combination with cisplatin or radiation.
β-Blocker Exposure in Pregnancy and Risk of Fetal Cardiac Anomalies
Authors: Lewei Duan, Angie Ng, Wansu Chen, Hillard T. Spencer, Jennifer Nguyen, Albert Y.-J. Shen, Ming-Sum Lee
Journal: JAMA Internal Medicine (2017)

This population-based cohort study examines the risk of fetal cardiac malformations associated with maternal β-blocker exposure.
Guideline: ACP and AAFP recommend systolic BP targets based on history and risk level in adults ≥ 60 years of age
Authors: Alena Shantsila, Gregory Y.H. Lip
Journal: Annals of Internal Medicine (2017)

Source Citation Qaseem A, Wilt TJ, Rich R, et al; Clinical Guidelines Committee of the American College of Physicians and the Commission on Health of the Public and Science of the American Academy of Family Physicians. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017;166:430-7.28135725
Immune Gene Expression Is Associated with Genomic Aberrations in Breast Cancer
Authors: Anton Safonov, Tingting Jiang, Giampaolo Bianchini, Balázs Győrffy, Thomas Karn, Christos Hatzis, Lajos Pusztai
Journal: Cancer Research (2017)

Abstract The presence of tumor-infiltrating lymphocytes (TIL) is a favorable prognostic factor in breast cancer, but what drives immune infiltration remains unknown. Here we examine if clonal heterogeneity, total mutation load, neoantigen load, copy number variations (CNV), gene- or pathway-level somatic mutations, or germline polymorphisms (SNP) are associated with immune metagene expression in breast cancer subtypes. Thirteen published immune metagenes correlated separately with genomic metrics in the three major breast cancer subtypes. We analyzed RNA-Seq, DNA copy number, mutation and germline SNP data of 627 ER+, 207 HER2+, and 191 triple-negative (TNBC) cancers from The Cancer Genome Atlas. P-values were adjusted for multiple comparisons, and permutation testing was used to assess false discovery rates. Increased immune metagene expression associated significantly with lower clonal heterogeneity estimated by MATH score in all subtypes and with a trend for lower overall mutation, neoantigen, and CNV loads in TNBC and HER2+ cancers. In ER+ cancers, mutation load, neoantigen load, and CNV load weakly but positively associated with immune infiltration, which reached significance for overall mutation load only. No highly recurrent single gene or pathway level mutations associated with immune infiltration. High immune gene expression and lower clonal heterogeneity in TNBC and HER2+ cancers suggest an immune pruning effect and equilibrium between immune surveillance and clonal expansion. Thus, immune checkpoint inhibitors may tip the balance in favor of immune surveillance in these cancers. Cancer Res; 77(12); 3317–24. ©2017 AACR.
Time for an overhaul at the World Medical Association
Authors: David Berger
Journal: BMJ (2017)

Serious questions must be asked about its standards of governance

On 21 October 2016 Ketan Desai began his one year tenure as president of the World Medical Association. The WMA is formed and funded by 111 national medical associations and describes itself as “an organization promoting the highest possible standards of medical ethics.”1 The incumbent president, however, is a controversial figure who has been charged with corruption in a Delhi court.2 3 4

Desai has not been convicted of corruption, denies all charges against him, and must be allowed the presumption of innocence. He has been exonerated in a number of previous corruption cases, and in one recent case in Lucknow the Uttar Pradesh government did not provide sanction to proceed (decision of Lucknow High Court in possession of author and The BMJ ). The current case in Delhi dates back several years, and Desai spent some months in prison on remand for this case in 2010.5 6 7 8 9 10

At that time the ethics committee of the Board of Governors in Supersession of the Medical Council of India, the body that registers …
Heme Oxygenase-1 (HO-1): A Novel KIT D816V-Dependent Target in Neoplastic Human Mast Cells (HMC-1).
Authors: Rudin Kondo, Matthias Mayerhofer, Karoline Gleixner, Anja Vales, Maria-Theresa Krauth, Sophia Derdak, Alexander Gruze, Winfried Pickl, Christian Sillaber, Khaled Greish, Hiroshi Maeda, Peter Valent
Journal: Blood (2005)
Fibromuscular Dysplasia
Authors: David P. Slovut, Jeffrey W. Olin
Journal: New England Journal of Medicine (2004)

Fibromuscular dysplasia is a noninflammatory process that may be difficult to distinguish from vasculitis. It develops in the middle and distal arterial segments, and especially in younger patients, it may cause renovascular hypertension, stroke, and cranial-nerve palsies. Treatment increasingly involves the use of percutaneous angioplasty.
Image Gallery: Xanthoma tuberosum
Authors: H. Yang, A. Tong
Journal: British Journal of Dermatology (2017)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, A 41‐year‐old man with primary aldosteronism presented with four nodules, one over each elbow and ankle, for 15 years (a). No family history of hypercholesterolaemia was revealed. The nodules gradually progressed in size despite well‐controlled hypercholesterolaemia with rosuvastatin. He reported no history of diabetes. The total cholesterol was 4·06 mmol L−1 (normal range 2·85–5·70), the triglyceride level was 1·19 mmol L−1 (0·45–1·70), low‐density lipoprotein cholesterol was 2·36 mmol L−1 (< 3·37), high‐density lipoprotein cholesterol was 1·25 mmol L−1 (93–1·81), glucose was 4·7 mmol L−1 (3·9–6·1) and uric acid was 386 mmol L−1 (210–416). Histological analysis of a biopsy specimen showed accumulation of large foam cells, and the diagnosis of tuberous xanthomas was confirmed (b; haematoxylin and eosin, original magnification × 200). The initial differential diagnoses, including ganglion cyst, lipoma and fibroma, were thus excluded.
TCTAP A-149 Clinical Outcomes of “Real World” Patients Receiving Novel Abluminal Coated Sirolimus Eluting Stent
Authors: Sameer Dani, Prathapkumar Natarajapillai, Apurva Vasavada, Jayachandran Thejus, Pritesh Parekh, Kamal Sharma, Rutvik Trivedi, Nirav Bhalani, Arvind Sharma, Chirag Sheth
Journal: Journal of the American College of Cardiology (2017)
TCTAP C-273 Pulmonary Hemorrhage During Transcatheter Aortic Valve Implantation
Authors: Ryosuke Higuchi, Tetsuya Tobaru, Kenichi Hagiya, Mike Saji, Keitaro Mahara, Itaru Takamisawa, Jun Shimizu, Nobuo Iguchi, Shuichiro Takanashi, Morimasa Takayama
Journal: Journal of the American College of Cardiology (2017)