tbuckley/cabot-search huggingface dataset:
Peer-Review Fraud — Hacking the Scientific Publication Process
Authors: Charlotte J Haug
Journal: New England Journal of Medicine (2015)

Interview with Dr. Charlotte Haug on the growing number of article retractions attributable to peer-review fraud. (07:09)Download In a new trend, increasing numbers of scientific articles are being retracted because of fake peer reviews — a type of fraud made possible by electronic manuscript submission systems and inspired by academia's publish-or-perish ethos.
Response to Open Peer Commentaries on “Prenatal Diagnosis and Abortion for Congenital Abnormalities: Is It Ethical to Provide One Without the Other?”
Authors: Angela Ballantyne, Ainsley Newson, Florencia Luna, Richard Ashcroft
Journal: The American Journal of Bioethics (2009)

We thank all the commentators to our paper, but here limit our remarks to those that directly challenge our argument. We have critiqued an unusual policy context in which prenatal diagnosis (PND) f...
Inhibition of SKOV-3 ovarian cancer cell proliferation by a C-terminal p21 fragment attached to thermally responsive Bac-7-ELP1
Authors: Iqbal Massodi, Drazen Raucher
Journal: Cancer Research (2008)

4909   Current treatment of solid tumors is limited by normal tissue tolerance and inherent tumor radio or chemo-resistance, resulting in a narrow therapeutic index. To overcome some of these limitations, it is necessary to consider alternative targeted therapeutic approaches for localized tumors that increase the specificity and efficacy and reduce the cytotoxicity in normal tissues.  In order to minimize nonspecific toxicity, we developed thermally responsive polypeptide inhibitors of the cell cycle, which can be targeted to the tumor site by applying local hyperthermia and inhibit proliferation of cancer cells. The design of this thermally responsive polypeptide is based on elastin-like polypeptide (ELP), which is soluble in aqueous solution below physiological temperature 37 °C, but aggregates when the temperature is raised above 41 °C.  Uptake of therapeutic macromolecules such as ELP into live eukaryotic cells is hindered by the lipophilic nature of the plasma membrane. One approach for delivering macromolecules or proteins into the target cells is to couple them to cell penetrating peptides (CPP). Therefore, we used a small CPP, Bac-7, fused to the thermally responsive elastin like polypeptide (ELP). The coding sequence for ELP was also modified by the addition of a small therapeutic peptide derived from p21, which acts as a cyclin-CDK inhibitor. The designed polypeptide (Bac-ELP1-p21) was then expressed and purified from  E. coli .  While 1 hour incubation with Bac-ELP1-p21 at 37  o C did not have any effect on SKOV-3 cell proliferation, use of hyperthermia inhibited the total cell number and cell proliferation rate by 80%. 24 hours after cell treatment, Bac-ELP1-p21 displayed a nuclear distribution and induced temperature dependent caspase activation. Cell cycle analysis revealed S and G2/M phase accumulation at the expense of G1 phase in cells treated at 42  o C as compared to 37  o C. Cell cycle inhibition was accompanied by a decrease in Rb phosphorylation levels in cells treated at 42  o C as compared to treatment at 37  o C, as confirmed by Western blot. In summary, we have shown that Bac-ELP1-p21 inhibits cell proliferation in response to hyperthermia, indicating that it has great potential as a thermally responsive targeted therapeutic.
Determination of cardiovascular velocities by dopplercardiometry: 1. The normal tracing and effects of age
Authors: D. M. Abelson, J. Jaffe, P. J. Murray
Journal: Cardiovascular Research (1971)

Journal Article Determination of cardiovascular velocities by dopplercardiometry: 1. The normal tracing and effects of age Get access Denis M. Abelson, Denis M. Abelson 2 From the Department of Clinical Cardiology, Royal Postgraduate Medical School, London, and the Department of Medicine, Graduate Hospital University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A. 2Present and reprint address: Lankenau Hospital, Lancaster and City Line Avenues, Philadelphia, Pa. 19151. U S A . Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph Jaffe, Joseph Jaffe From the Department of Clinical Cardiology, Royal Postgraduate Medical School, London, and the Department of Medicine, Graduate Hospital University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Penelope J. Murray Penelope J. Murray From the Department of Clinical Cardiology, Royal Postgraduate Medical School, London, and the Department of Medicine, Graduate Hospital University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 5, Issue 4, October 1971, Pages 535–544, https://doi.org/10.1093/cvr/5.4.535 Published: 01 October 1971
Anastrozole-Induced Carpal Tunnel Syndrome: Results From the International Breast Cancer Intervention Study II Prevention Trial
Authors: Francesco Spagnolo, Ivana Sestak, Anthony Howell, John F. Forbes, Jack Cuzick
Journal: Journal of Clinical Oncology (2015)

Purpose Carpal tunnel syndrome (CTS) occurs when the median nerve is compressed at the wrist in the carpal tunnel. It has been suggested that hormonal risk factors may be involved in the pathogenesis of CTS, and a higher incidence of CTS has been reported in randomized clinical trials with aromatase inhibitors (AIs) compared with tamoxifen. Patients and Methods This was an exploratory analysis of the International Breast Cancer Intervention Study II, a double-blind randomized clinical trial in which women at increased risk of breast cancer were randomly assigned to receive anastrozole or placebo. This is the first report of risk factors for and characteristics of CTS in women taking an AI in a placebo-controlled trial. Results Overall, 96 participants with CTS were observed: 65 (3.4%) in the anastrozole arm and 31 (1.6%) in the placebo arm (odds ratio, 2.16 [1.40 to 3.33]; P &lt; .001). Ten participants were reported as having severe CTS, of which eight were taking anastrozole (P = .08). Eighteen women (0.9%) in the anastrozole arm and six women (0.3%) in the placebo arm reported surgical intervention, which was significantly different (odds ratio, 3.06 [1.21 to 7.72], P = .018). Six women discontinued with the allocated treatment because of the onset of CTS. Apart from treatment allocation, a high body mass index and an a prior report of musculoskeletal symptoms after trial entry were the only other risk factors for CTS identified in these postmenopausal women. Conclusions The use of anastrozole was associated with a higher incidence of CTS but few participants required surgery. Further investigations are warranted into the risk factors and treatment of AI-induced CTS.
Evaluation of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma
Authors: Maria Vassilakopoulou, Margaritis Avgeris, Vamsidhar Velcheti, Vassiliki Kotoula, Theodore Rampias, Kyriakos Chatzopoulos, Christos Perisanidis, Christos K. Kontos, Aris I. Giotakis, Andreas Scorilas, David Rimm, Clarence Sasaki, George Fountzilas, Amanda Psyrri
Journal: Clinical Cancer Research (2015)

Programmed death-ligand 1 (PD-L1; also known as CD274 or B7-H1) expression represents a mechanism of immune escape for cancer. Our purpose was to characterize tumor PD-L1 expression and associated T-cell infiltration in primary laryngeal squamous cell carcinomas (SCC).A well-annotated cohort of 260 operable primary laryngeal SCCs [formalin-fixed paraffin-embedded (FFPE) specimens] was morphologically characterized for stromal tumor-infiltrating lymphocytes (TIL), on hematoxylin/eosin-stained whole sections and for PD-L1 mRNA expression by qRT-PCR in FFPE specimens. For PD-L1 protein expression, automated quantitative protein analysis (AQUA) was applied on tissue microarrays consisting of two cores from these tumors. In addition, PD-L1 mRNA expression in fresh-frozen tumors and normal adjacent tissue specimens was assessed in a second independent cohort of 89 patients with primary laryngeal SCC.PD-L1 mRNA levels were upregulated in tumors compared with surrounding normal tissue (P = 0.009). TILs density correlated with tumor PD-L1 AQUA levels (P = 0.021). Both high TILs density and high PD-L1 AQUA levels were significantly associated with superior disease-free survival (DFS; TILs: P = 0.009 and PD-L1: P = 0.044) and overall survival (OS; TILs: P = 0.015 and PD-L1: P = 0.059) of the patients and retained significance in multivariate analysis.Increased TILs density and PD-L1 levels are associated with better outcome in laryngeal squamous cell cancer. Assessment of TILs and PD-L1 expression could be useful to predict response to immune checkpoint inhibitors.
Antiviral therapy in chronic hepatitis B viral infection during pregnancy: A systematic review and meta‐analysis
Authors: Robert S. Brown, Brian J. McMahon, Anna S.F. Lok, John B. Wong, Ahmed T. Ahmed, Mohamed A. Mouchli, Zhen Wang, Larry J. Prokop, Mohammad Hassan Murad, Khaled Mohammed
Journal: Hepatology (2015)

Perinatal or mother‐to‐child transmission (MTCT) of hepatitis B virus (HBV) remains the major risk factor for chronic HBV infection worldwide. In addition to hepatitis B immune globulin and vaccination, oral antiviral therapies in highly viremic mothers can further decrease MTCT of HBV. We conducted a systematic review and meta‐analysis to synthesize the evidence on the efficacy and maternal and fetal safety of antiviral therapy during pregnancy. A protocol was developed by the American Association for the Study of Liver Diseases guideline writing committee. We searched multiple databases for controlled studies that enrolled pregnant women with chronic HBV infection treated with antiviral therapy. Outcomes of interest were reduction of MTCT and adverse outcomes to mothers and newborns. Study selection and data extraction were done by pairs of independent reviewers. We included 26 studies that enrolled 3622 pregnant women. Antiviral therapy reduced MTCT, as defined by infant hepatitis B surface antigen seropositivity (risk ratio = 0.3, 95% confidence interval 0.2‐0.4) or infant HBV DNA seropositivity (risk ratio = 0.3, 95% confidence interval 0.2‐0.5) at 6‐12 months. No significant differences were found in the congenital malformation rate, prematurity rate, and Apgar scores. Compared to control, lamivudine or telbivudine improved maternal HBV DNA suppression at delivery and during 4‐8 weeks' postpartum follow‐up. Tenofovir showed improvement in HBV DNA suppression at delivery. No significant differences were found in postpartum hemorrhage, cesarean section, and elevated creatinine kinase rates. Conclusions: Antiviral therapy improves HBV suppression and reduces MTCT in women with chronic HBV infection with high viral load compared to the use of hepatitis B immunoglobulin and vaccination alone; the use of telbivudine, lamivudine, and tenofovir appears to be safe in pregnancy with no increased adverse maternal or fetal outcome. (H epatology 2016;63:319–333)
Abstract #4697: The role of downstream signaling pathways of the epidermal growth factor receptor for artesunate\#8217;s activity in cancer cells
Authors: V. Badireenath Konkimalla, James McCubrey, Thomas Efferth
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Epidermal growth factor (EGF) and its receptor EGFR (epidermal growth factor receptor) plays a key role in the regulation of essential normal cellular processes and in the pathophysiology of hyperproliferative diseases such as cancer. EGFR-coupled Ras>Raf>MEK>ERK pathway are known to affect the survival of cancer cells upon chemotherapeutic treatment. Artesunate is an antimalarial drug that has been show to exhibit profound inhibitory activity against cancer cells. In the present investigation, we applied a combination of mathematical approach followed by experimental validation to study the role of EGFR downstream signaling pathways for the response of tumor cells to artesunate\#8217;s activity. The genome-wide mRNA expression profiling of the NCI cell lines and the IC50 of artesunate on these cell lines has been reported and deposited at the NCI database (http://dtp.nci.nih.gov). Initially as a mathematical approach, the IC50 values of the NCI cell line panel for artesunate were correlated with the microarray-based mRNA expression values of genes involved in the EGFR pathway. The log10IC50 values for artesunate on these NCI cell lines were in a range of -6.609 to -4.0M. Candidate genes identified by this approach were experimentally validated by transfecting cell lines with corresponding cDNA vectors. [3H]-thymidine incorporation assay and flow cytometric analysis were performed on these transfected cell lines with or without artesunate treatment. From both mathematical and experiemental approaches, it was observed that the mRNA expression of genes belonging to the Ras>Raf>MEK>ERK pathway significantly correlated with the IC50 values for artesunate, indicating that this signaling route might play a role for the response of tumor cells to artesunate. Furthermore, the gene expression of the PIK3R2>Akt1>BAD or >RPS6KA5 and CBLC pathways also significantly correlated with response of tumor cell lines to artesunate. The mRNA expression of genes belonging to the CRK>ABL1 signaling route did not correlate with artesunate\#8217;s activity in cancer cells in both of our approaches. In conclusion, as exemplarily shown for artesunate, such a strategy of applying combined approach in identifying signal transduction pathways involved in the response of tumor cells to cytotoxic compounds might aid in balancing the declining cure rates and foster the development of novel molecular targeted therapies for cancer treatment.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4697.
Lymphocyte Development from Stem Cells
Authors: K Ikuta, N Uchida, J Friedman, I L Weissman
Journal: Annual Review of Immunology (1992)

Highly enriched pluripotent and multipotent hematopoietic stem cells (HSCs) are isolated from bone marrow and fetal liver as Thy-1loLin-Sca-1+ cells. Pluripotent HSCs express c-kit receptor on their surface, but the generation and proliferation of early fetal HSCs take place in the absence of steel factor. T precursor cells migrate into the fetal thymus by chemotactic mechanism. CD4lo precursors represent a newly defined phase of T-cell development in the thymus between the bone marrow-derived stem cells and the CD4-8- intrathymic precursors. Only fetal, but not adult, HSCs have the capacity to differentiate into V gamma 3+ and V gamma 4+ T cells under the fetal thymic microenvironment, and HSC themselves may lose some of their developmental potential during ontogeny. It is postulated that HSCs are the locus of a complicated but precise developmental clock that may determine both the time-dependent closure of some gene loci (e.g. V gamma 3 and V gamma 4 T cell receptor, and embryonic and fetal globin) and the activation of others (e.g. the N nucleotide insertion machinery).
XPO1 Inhibition Enhances Radiation Response in Preclinical Models of Rectal Cancer
Authors: Isabel Ferreiro-Neira, Nancy E. Torres, Lukas F. Liesenfeld, Carlos H.F. Chan, Tristan Penson, Yosef Landesman, William Senapedis, Sharon Shacham, Theodore S. Hong, James C. Cusack
Journal: Clinical Cancer Research (2015)

Combination of radiation with radiosensitizing chemotherapeutic agents improves outcomes for locally advanced rectal cancer. Current treatment includes 5-fluorouracil-based chemoradiation prior to surgical resection; however pathologic complete response varies from 15% to 20%, prompting the need to identify new radiosensitizers. Exportin 1 (XPO1, also known as chromosome region 1, CRM1) mediates the nuclear export of critical proteins required for rectal cancer proliferation and treatment resistance. We hypothesize that inhibition of XPO1 may radiosensitize cancer cells by altering the function of these critical proteins resulting in decreased radiation resistance and enhanced antitumoral effects.To test our hypothesis, we used the selective XPO1 inhibitor, selinexor, to inhibit nuclear export in combination with radiation fractions similar to that given in clinical practice for rectal cancer: hypofractionated short-course radiation dosage of 5 Gy per fraction or the conventional long-course radiation dosage of 1 Gy fractions. Single and combination treatments were tested in colorectal cancer cell lines and xenograft tumor models.Combination treatment of radiotherapy and selinexor resulted in an increase of apoptosis and decrease of proliferation compared with single treatment, which correlated with reduced tumor size. We found that the combination promoted nuclear survivin accumulation and subsequent depletion, resulting in increased apoptosis and enhanced radiation antitumoral effects.Our findings suggest a novel therapeutic option for improving radiation sensitivity in the setting of rectal cancer and provide the scientific rationale to evaluate this combination strategy for clinical trials.
Trastuzumab emtansine (T-DM1) renders HER2 <sup>+</sup> breast cancer highly susceptible to CTLA-4/PD-1 blockade
Authors: Philipp Müller, Matthias Kreuzaler, Tarik Khan, Daniela S. Thommen, Kea Martin, Katharina Glatz, Spasenija Savic, Nadia Harbeck, Ulrike Nitz, Oleg Gluz, Michael von Bergwelt-Baildon, Hans Kreipe, Sai Reddy, Matthias Christgen, Alfred Zippelius
Journal: Science Translational Medicine (2015)

Targeted drug delivery with antibody-drug conjugates such as the HER2-directed ado-trastuzumab emtansine (T-DM1) has emerged as a powerful strategy for cancer therapy. We show that T-DM1 is particularly effective in eliciting antitumor immunity in patients with early breast cancer (WSG-ADAPT trial) and in a HER2-expressing orthotopic tumor model. In the latter, despite primary resistance to immunotherapy, combined treatment with T-DM1 and anti-CTLA-4/PD-1 (cytotoxic T lymphocyte-associated protein-4/programmed cell death protein-1) was curative because it triggered innate and adaptive immunity. Tumor rejection was accompanied by massive T cell infiltration, TH1 (T helper 1) cell polarization, and, notably, a substantial increase in regulatory T cells. Depletion of regulatory T cells resulted in inflammation and tissue damage, implying their essential role in protecting the host during therapy. This study provides insights into the mechanisms of T-DM1's therapeutic activity and a rationale for potential therapeutic combination strategies with immunotherapy.
The PsychENCODE project
Authors: Schahram Akbarian, Chunyu Liu, James A Knowles, Flora M Vaccarino, Peggy J Farnham, Gregory E Crawford, Andrew E Jaffe, Dalila Pinto, Stella Dracheva, Daniel H Geschwind, Jonathan Mill, Angus C Nairn, Alexej Abyzov, Sirisha Pochareddy, Shyam Prabhakar, Sherman Weissman, Patrick F Sullivan, Matthew W State, Zhiping Weng, Mette A Peters, Kevin P White, Mark B Gerstein, Anahita Amiri, Chris Armoskus, Allison E Ashley-Koch, Taejeong Bae, Andrea Beckel-Mitchener, Benjamin P Berman, Gerhard A Coetzee, Gianfilippo Coppola, Nancy Francoeur, Menachem Fromer, Robert Gao, Kay Grennan, Jennifer Herstein, David H Kavanagh, Nikolay A Ivanov, Yan Jiang, Robert R Kitchen, Alexey Kozlenkov, Marija Kundakovic, Mingfeng Li, Zhen Li, Shuang Liu, Lara M Mangravite, Eugenio Mattei, Eirene Markenscoff-Papadimitriou, Fábio C P Navarro, Nicole North, Larsson Omberg, David Panchision, Neelroop Parikshak, Jeremie Poschmann, Amanda J Price, Michael Purcaro, Timothy E Reddy, Panos Roussos, Shannon Schreiner, Soraya Scuderi, Robert Sebra, Mikihito Shibata, Annie W Shieh, Mario Skarica, Wenjie Sun, Vivek Swarup, Amber Thomas, Junko Tsuji, Harm van Bakel, Daifeng Wang, Yongjun Wang, Kai Wang, Donna M Werling, A Jeremy Willsey, Heather Witt, Hyejung Won, Chloe C Y Wong, Gregory A Wray, Emily Y Wu, Xuming Xu, Lijing Yao, Geetha Senthil, Thomas Lehner, Pamela Sklar, Nenad Sestan
Journal: Nature Neuroscience (2015)
Comparison of spinal magnetic resonance imaging and myelography in cancer patients.
Authors: C Hagenau, W Grosh, M Currie, R G Wiley
Journal: Journal of Clinical Oncology (1987)

Spinal involvement by systemic malignancy is common, and often leads to extradural compression of the spinal cord and/or nerve roots by metastases. Rapid, anatomically accurate diagnosis is essential to the successful management of these patients. We compared spinal magnetic resonance imaging (MRI) with conventional myelography in a series of 31 cancer patients being evaluated for myelopathy (N = 10), or back/radicular pain (N = 21). All patients were evaluated between April 1985 and July 1986, and underwent both studies within ten days of each other (median, two days). MRI was performed on a 0.5 Tesla Technicare unit with a body surface coil, and results compared with standard contrast myelography. All studies were reviewed separately and in a "blinded" fashion. MRI and myelography were comparable in detecting large lesions that produced complete subarachnoid block (five of ten patients with myelopathy, three of twenty-one patients with back/radicular pain). In 19 of 31 patients, smaller but clinically significant extradural lesions were found. In nine of 19 cases, these lesions were demonstrated equally well by both modalities; in nine of 19 cases, these lesions were demonstrated by myelography alone; in one of 19, a lesion was demonstrated by MRI alone. Given our current technology, myelography appeared superior to MRI as a single imaging modality. However, MRI may be an alternative in patients where total myelography is technically impossible or unusually hazardous.
Intradermal trivalent influenza vaccine with topical imiquimod for cross-protection against non-vaccine and antigenically drifted virus: a double-blind, randomised controlled trial
Authors: Ivan F N Hung, Anna J Zhang, Kelvin K W To, Jasper F W Chan, Patrick Li, Ricky Zhang, Tin-Lun Wong, Tuen-Ching Chan, Lok-Wun Chan, Chi-Ngo Geo Yiu, Ka-Lun Kong, Chun-Yuan Chan, Pak-Yiu Fong, Chun-Fung Leung, Kar-Ching Hui, Johnson Y N Lau, Honglin Chen, Kwok-Yung Yuen, Pak-Chung Alex Yeung, Wing-Ki Tsang, Abe Ngan, Grace Yung, Harrison Chan, Kwok-Hung Chan
Journal: The Lancet (2015)
Extensively drug-resistant tuberculosis in a young child after travel to India
Authors: Nicole Salazar-Austin, Alvaro A Ordonez, Alice Jenh Hsu, Jane E Benson, Mahadevappa Mahesh, Elizabeth Menachery, Jafar H Razeq, Max Salfinger, Jeffrey R Starke, Aaron M Milstone, Nicole Parrish, Eric L Nuermberger, Sanjay K Jain
Journal: The Lancet Infectious Diseases (2015)