tbuckley/cabot-search huggingface dataset:
Editorial expression of concern
Authors: Orla M. Smith
Journal: Science Translational Medicine (2020)

On 3 June 2015, Science Translational Medicine published the Research Article “[Regulator of G protein signaling 5 is a determinant of gestational hypertension and preeclampsia][1]” by V. Holobotovskyy, Y. S. Chong, J. Burchell, B. He, M. Phillips, L. Leader, T. V. Murphy, S. L. Sandow, D. J. McKitrick, A. K. Charles, M. Tare, L. F. Arnolda, R. Ganss ([ 1 ][2]). Recently, it was brought to our attention that the conductance patterns for uterine and femoral arteries depicted in Figs. 2 and S3, as well as Figs. 3 and S4, are very similar. When Science Translational Medicine contacted the corresponding author to request the raw data for these figures, the authors responded that the raw data were no longer available due to a computer malfunction and lack of any backup files. The figures in question are very similar but may be within the range of naturally occurring variation given that each pair of measurements was conducted simultaneously in the same animal. However, Science Translational Medicine is publishing this Editorial Expression of Concern to alert our readers to this similarity and to the lack of raw data, which means the veracity of these figures cannot be ascertained.

1.  [↵][3]1.   V. Holobotovskyy,     2.   Y. S. Chong,     3.   J. Burchell,     4.   B. He,     5.   M. Phillips,     6.   L. Leader,     7.   T. V. Murphy,     8.   S. L. Sandow,     9.   D. J. McKitrick,     10.  A. K. Charles,     11.  M. Tare,     12.  L. F. Arnolda,     13.  R. Ganss
        , Regulator of G protein signaling 5 is a determinant of gestational hypertension and preeclampsia. Sci. Transl. Med. 7, 290ra88 (2015).

 [1]: https://stm.sciencemag.org/content/7/290/290ra88
 [2]: #ref-1
 [3]: #xref-ref-1-1 View reference 1 in text
Programmed Death-Ligand 1 Immunohistochemistry Assay Comparison Studies in NSCLC: Characterization of the 73-10 Assay
Authors: Hans Juergen Grote, Zheng Feng, Michael Schlichting, Christoph Helwig, Mary Ruisi, Hulin Jin, Juergen Scheuenpflug, Claudia-Nanette Gann, Zhen Su, Martin Reck, Everett E. Vokes, Keith M. Kerr
Journal: Journal of Thoracic Oncology (2020)

Several programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assays have been developed independently within clinical programs for therapeutic anti-programmed cell death protein 1 (anti-PD-1) or PD-L1 antibodies, necessitating assessment of assay comparability. We characterized the Dako PD-L1 IHC 73-10 assay used in clinical trials of avelumab (anti-PD-L1) or bintrafusp alfa (M7824; bifunctional immunotherapy) and compared it with the Dako PD-L1 IHC 22C3 pharmDx assay, an approved companion diagnostic for pembrolizumab monotherapy in patients with advanced NSCLC.Formalin-fixed, paraffin-embedded NSCLC tumor samples from a commercial source and from the JAVELIN Solid Tumor phase 1 trial of avelumab (NCT01772004) were stained using the 73-10 and 22C3 IHC assays with a standard protocol.Both assays displayed expected PD-L1 staining patterns. In 148 commercial NSCLC samples, the 73-10 assay stained greater than or equal to 1%, greater than or equal to 50%, and greater than or equal to 80% of tumor cells as PD-L1+ in 64.2%, 36.5%, and 23.6% of the samples, respectively, whereas the 22C3 assay stained 20.3% of the samples as greater than or equal to 50% PD-L1+. In 83 NSCLC clinical trial samples, the 73-10 assay stained 79.5% and 31.3% of the samples as greater than or equal to 1% and greater than or equal to 80% PD-L1+, respectively, whereas the 22C3 assay stained 59.0% and 21.7% as greater than or equal to 1% and greater than or equal to 50% PD-L1+, respectively. Efficacy of avelumab was similar in the subgroups classified with the 73-10 and 22C3 assays using greater than or equal to 80% and greater than or equal to 50% PD-L1+ cutoffs, with objective response rates of 26.9% and 33.3%, respectively.The 73-10 assay demonstrated high sensitivity for PD-L1 staining, and staining was comparable between the greater than or equal to 80% cutoff of the 73-10 assay and greater than or equal to 50% cutoff of the 22C3 assay.
Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603)
Authors: Shota Fukuoka, Hiroki Hara, Naoki Takahashi, Takashi Kojima, Akihito Kawazoe, Masako Asayama, Takako Yoshii, Daisuke Kotani, Hitomi Tamura, Yuichi Mikamoto, Nami Hirano, Masashi Wakabayashi, Shogo Nomura, Akihiro Sato, Takeshi Kuwata, Yosuke Togashi, Hiroyoshi Nishikawa, Kohei Shitara
Journal: Journal of Clinical Oncology (2020)

This is a phase Ib trial of regorafenib plus nivolumab for gastric and colorectal cancer.Enrolled patients received regorafenib plus nivolumab in a dose-finding part to estimate the maximum tolerated dose. Additional patients were enrolled in a dose-expansion part. Regorafenib of 80-160 mg was administered once daily for 21 days on/7 days off with nivolumab 3 mg/kg every 2 weeks. The primary end point was dose-limiting toxicity (DLT) during the first 4 weeks to estimate the recommended dose.Fifty patients (25 each with gastric and colorectal cancer) were enrolled. All patients had received ≥ 2 previous lines of chemotherapy, including anti-angiogenetic inhibitors in 96% of patients. Seven patients with gastric cancer had previously been treated with immune checkpoint inhibitors. One patient had microsatellite instability-high colorectal cancer, whereas the remaining patients had microsatellite stable or mismatch repair-proficient tumors. Three DLTs (grade 3 colonic perforation, maculopapular rash, and proteinuria) were observed with regorafenib 160 mg; none were observed with 80 or 120 mg. During the dose-expansion part, regorafenib dose was reduced from 120 to 80 mg because of frequent maculopapular rash. The common grade ≥ 3 treatment-related adverse events were rash (12%), proteinuria (12%), and palmar-plantar erythrodysesthesia (10%). Objective tumor response was observed in 20 patients (40%), including 11 with gastric cancer (44%) and 9 with colorectal cancer (36%). Median progression-free survival was 5.6 and 7.9 months in patients with gastric and colorectal cancer, respectively.The combination of regorafenib 80 mg plus nivolumab had a manageable safety profile and encouraging antitumor activity in patients with gastric and colorectal cancer, which warrants additional investigations in larger cohorts.
Lineage-Specific Epigenomic and Genomic Activation of Oncogene HNF4A Promotes Gastrointestinal Adenocarcinomas
Authors: Jian Pan, Tiago C. Silva, Nicole Gull, Qian Yang, Jasmine T. Plummer, Stephanie Chen, Kenji Daigo, Takao Hamakubo, Sigal Gery, Ling-Wen Ding, Yan-Yi Jiang, Shaoyan Hu, Li-Yan Xu, En-Min Li, Yanbing Ding, Samuel J. Klempner, Simon A. Gayther, Benjamin P. Berman, H. Phillip Koeffler, De-Chen Lin
Journal: Cancer Research (2020)

Abstract Gastrointestinal adenocarcinomas (GIAC) of the tubular gastrointestinal (GI) tract including esophagus, stomach, colon, and rectum comprise most GI cancers and share a spectrum of genomic features. However, the unified epigenomic changes specific to GIAC are poorly characterized. Using 907 GIAC samples from The Cancer Genome Atlas, we applied mathematical algorithms to large-scale DNA methylome and transcriptome profiles to reconstruct transcription factor (TF) networks and identify a list of functionally hyperactive master regulator (MR) TF shared across different GIAC. The top candidate HNF4A exhibited prominent genomic and epigenomic activation in a GIAC-specific manner. A complex interplay between the HNF4A promoter and three distal enhancer elements was coordinated by GIAC-specific MRTF including ELF3, GATA4, GATA6, and KLF5. HNF4A also self-regulated its own promoter and enhancers. Functionally, HNF4A promoted cancer proliferation and survival by transcriptional activation of many downstream targets, including HNF1A and factors of interleukin signaling, in a lineage-specific manner. Overall, our study provides new insights into the GIAC-specific gene regulatory networks and identifies potential therapeutic strategies against these common cancers. Significance: These findings show that GIAC-specific master regulatory transcription factors control HNF4A via three distal enhancers to promote GIAC cell proliferation and survival.
Cardiac Masses in a Patient With Pancreatic Adenocarcinoma and a History of Breast Carcinoma
Authors: Sara Nunnery, Wendy Bottinor, Satya Das
Journal: JAMA Oncology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Video consultations for triage of patients with covid-19
Authors: Oommen John
Journal: BMJ (2020)

<b>Objective:</b> The rise in body mass index (BMI) during adulthood increases the risk for metabolic disorders, functional limitations and disability in old age. This twin study examined prospectively whether genetic and environmental influences on women’s BMI also account for mobility 29 years later. <b>Design:</b> The sample consisted of 103 monozygotic and 114 dizygotic pairs of twin sisters reared together. <b>Main outcomes measures:</b> BMI was initially evaluated in year the 1975, when the women were aged 42.6±3.4 years, and was followed-up in 1981, 1990, 2001 and 2004. Mobility was evaluated using the standardized 6-minute walking test in 2001, when the women were aged 68.6±3.2 years, and followed-up 3 years later. We investigated how genetic and environmental influences on adult BMI accounted for mobility in old age using a genetic latent growth modeling approach. <b>Results:</b> During the follow-up period, BMI increased by 17%. Midlife BMI was a significant predictor of mobility 29 years later. Genetic influences on BMI level and its rate-of-change accounted for 37% and 25% respectively, of the genetic influences on mobility later in life. The corresponding environmental influences on BMI level and its rate-of-change were 35% and 22%. <b>Conclusion:</b> Genes predisposing to higher BMI across middle age increase the risk for poorer mobility in old age. Identifying those genes could lead to interventions targeted at preventing obesity and mobility loss later in life. However, modification of environmental factors, e.g. exercise and nutrition remain the most feasible ways of influencing BMI and mobility across the life span.
Startle modulation in children with posttraumatic stress disorder
Authors: E M Ornitz, R S Pynoos
Journal: American Journal of Psychiatry (1989)

Startle responses to bursts of white noise were recorded as blink reflexes 17-21 months after a traumatic event in six children with posttraumatic stress disorder (PTSD) and in six normal control children. A seventh child with PTSD was studied on four occasions during the 2 years following a stressful event. The startle responses were modulated by nonstartling acoustic prestimulation in order to study the inhibitory and facilitatory modulation of startle reaction by brainstem mechanisms. The children with PTSD experienced a significant loss of the normal inhibitory modulation of startle response, suggesting that the traumatic experience had induced a long-lasting brainstem dysfunction.
Abstract #838: Efficacy of MDX-1110, an anti-Fucosyl-GM1 antibody in a SCLC tumor model
Authors: Bingliang Chen, Alison Witte, James Phillips, Jenny Chang, Meghan Greenbaum, Orville Cortez, Chin Pan, Jon Terrett, Pina Cardarelli
Journal: Cancer Research (2009)

MDX-1110 is a fully human, non-fucosylated, IgG1 monoclonal antibody which specifically recognizes the sphingolipid monosialoganglioside fucosyl-GM1. Since fucosyl-GM1 is expressed on most small cell lung carcinomas (SCLC) and is minimally expressed on healthy tissues, it presents an attractive target for therapeutic intervention. In vivo and in vitro studies of MDX-1110 anti-tumor activity demonstrate high potency and efficacy, mediated by antibody dependant cellular cytotoxicity (ADCC) and complement dependant cytotoxicity (CDC). ELISA with purified antigen has been used to verify robust and exquisitely selective binding of MDX-1110 to fucosyl-GM1 when compared to the closely related ganglioside GM1. FACS of human SCLC cell lines such as DMS79, H526 and H740 showed expression of fucosyl-GM1 and dose dependant MDX-1110 binding. Assays of antibody effector function result in potent killing of antigen positive cells. Both ADCC and CDC activities typically result in greater than 50% cell lysis with low nM EC50s. Based on these findings a therapeutic DMS79 tumor model was established in B17 SCID mice and the in vivo anti-tumor efficacy of MDX-1110 both as a monotherapy and in combination with standard of care chemotherapeutic agents was determined. DMS79 cells were implanted subcutaneously and treatments began when tumor volumes reached approximately 200 mm3. Five doses of MDX-1110 monotherapy at 0.01, 0.1, 0.3, 1 and 3 mg/kg were administered. Suppression of tumor growth was maximal at 0.3 mg/kg and was maintained to day 36 post-implantation. Subsequently, MDX-1110 at 0.3 mg/kg was evaluated in combination with cisplatin, administered at 3 mg/kg for 4 doses. While MDX-1110 alone was more efficacious than cisplatin, the combination of the two therapies exhibited obviously enhanced activity and suppressed tumor growth to 76 days post-implantation. In conclusion, MDX-1110 is highly selective for fucosyl-GM1 and exhibits potent cytotoxic effector function against antigen positive cells in vitro. MDX-1110 demonstrates highly potent in vivo anti-tumor efficacy as a monotherapeutic and results in greatly enhanced activity with standard of care chemotherapeutic agents.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 838.
Start of the influenza season 2008-9 in Europe - increasing influenza activity moving from West to East dominated by A(H3N2)
Authors: N Goddard, P Zucs, B Ciancio, F Plata, O Hungnes, A Mazick, A Meijer, A Hay, R Daniels, A Nicoll, M Zambon
Journal: Eurosurveillance (2009)

The influenza season 2008-9 started in week 49 of 2008 and is so far characterised by influenza virus type A subtype H3N2. Isolates of this subtype that were tested proved susceptible to neuraminidase inhibitors, but resistant to M2 inhibitors. The circulating A(H3N2) viruses are antigenically similar to the component in the current northern hemisphere influenza vaccine.
ACE2 Expression in Pancreas May Cause Pancreatic Damage After SARS-CoV-2 Infection
Authors: Furong Liu, Xin Long, Bixiang Zhang, Wanguang Zhang, Xiaoping Chen, Zhanguo Zhang
Journal: Clinical Gastroenterology and Hepatology (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus that causes coronavirus disease 2019 (COVID-19) in human beings, has caused a serious public health issue.1 Attention to pancreatic injury is lacking, which may impact patients' prognosis. In this study, we explored the expression and distribution of angiotensin-converting enzyme 2 (ACE2), the receptor of SARS-CoV-2, in the pancreas. Combined with clinical data, we showed that pancreatic injury can occur in some COVID-19 patients.
Assessment of Outcomes With Pulsed Dye Laser Treatment of Port-Wine Stains Located Proximally vs Distally on Extremities
Authors: Wenxin Yu, Jiafang Zhu, Yue Han, Shih-Jen Chang, Ying Shang, Gang Ma, Xiaoxi Lin
Journal: JAMA Dermatology (2020)

This nonrandomized clinical trial evaluates the morphological and anatomical features of port-wine stains treated by pulsed dye laser to assess differences in treatment efficacy based on proximal vs distal location on extremities.
Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young
Authors: Thomas J Oxley, J Mocco, Shahram Majidi, Christopher P Kellner, Hazem Shoirah, I Paul Singh, Reade A De Leacy, Tomoyoshi Shigematsu, Travis R Ladner, Kurt A Yaeger, Maryna Skliut, Jesse Weinberger, Neha S Dangayach, Joshua B Bederson, Stanley Tuhrim, Johanna T Fifi
Journal: New England Journal of Medicine (2020)

Covid-19 CasesTo rapidly communicate information on the global clinical effort against Covid-19, the Journal has initiated a series of case reports that offer important teaching points or novel findings.The case reports should be viewed as observations rather than as recommendations for evaluation or treatment.In the interest of timeliness, these reports are evaluated by in-house editors, with peer review reserved for key points as needed.
The sputum microbiome, airway inflammation, and mortality in chronic obstructive pulmonary disease
Authors: Alison J. Dicker, Jeffrey T.J. Huang, Mike Lonergan, Holly R. Keir, Christopher J. Fong, Brandon Tan, Andrew J. Cassidy, Simon Finch, Hana Mullerova, Bruce E. Miller, Ruth Tal-Singer, James D. Chalmers
Journal: Journal of Allergy and Clinical Immunology (2020)
Analysis of Released Circulating Tumor Cells During Surgery for Non-Small Cell Lung Cancer
Authors: Menno Tamminga, Sanne de Wit, Caroline van de Wauwer, Hilda van den Bos, Joost F. Swennenhuis, Theo J. Klinkenberg, T. Jeroen N. Hiltermann, Kiki C. Andree, Diana C.J. Spierings, Peter M. Lansdorp, Anke van den Berg, Wim Timens, Leon W.M.M. Terstappen, Harry J.M. Groen
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Tumor cells from patients with lung cancer are expelled from the primary tumor into the blood, but difficult to detect in the peripheral circulation. We studied the release of circulating tumor cells (CTCs) during surgery to test the hypothesis that CTC counts are influenced by hemodynamic changes (caused by surgical approach) and manipulation. Experimental Design: Patients undergoing video-assisted thoracic surgery (VATS) or open surgery for (suspected) primary lung cancer were included. Blood samples were taken before surgery (T0) from the radial artery (RA), from both the RA and pulmonary vein (PV) when the PV was located (T1) and when either the pulmonary artery (T2 open) or the PV (T2 VATS) was dissected. The CTCs were enumerated using the CellSearch system. Single-cell whole-genome sequencing was performed on isolated CTCs for aneuploidy. Results: CTCs were detected in 58 of 138 samples (42%) of 31 patients. CTCs were more often detected in the PV (70%) compared with the RA (22%, P &amp;lt; 0.01) and in higher counts (P &amp;lt; 0.01). After surgery, the RA but not the PV showed less often CTCs (P = 0.02). Type of surgery did not influence CTC release. Only six of 496 isolated CTCs showed aneuploidy, despite matched primary tumor tissue being aneuploid. Euploid so-called CTCs had a different morphology than aneuploid. Conclusions: CTCs defined by CellSearch were identified more often and in higher numbers in the PV compared with the RA, suggesting central clearance. The majority of cells in the PV were normal epithelial cells and outnumbered CTCs. Release of CTCs was not influenced by surgical approach.
Efficacy of oral zinc and nicotinamide as maintenance therapy for mild/moderate hidradenitis suppurativa: A controlled retrospective clinical study
Authors: Elisa Molinelli, Valerio Brisigotti, Anna Campanati, Claudia Sapigni, Alfredo Giacchetti, Carlo Cota, Annamaria Offidani
Journal: Journal of the American Academy of Dermatology (2020)
Classification of Opioid Dependence, Abuse, or Overdose in Opioid-Naive Patients as a “Never Event”
Authors: Richard J. Barth, Jennifer F. Waljee
Journal: JAMA Surgery (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Olaparib for Metastatic Castration-Resistant Prostate Cancer
Authors: Johann de Bono, Joaquin Mateo, Karim Fizazi, Fred Saad, Neal Shore, Shahneen Sandhu, Kim N. Chi, Oliver Sartor, Neeraj Agarwal, David Olmos, Antoine Thiery-Vuillemin, Przemyslaw Twardowski, Niven Mehra, Carsten Goessl, Jinyu Kang, Joseph Burgents, Wenting Wu, Alexander Kohlmann, Carrie A. Adelman, Maha Hussain
Journal: New England Journal of Medicine (2020)

Multiple loss-of-function alterations in genes that are involved in DNA repair, including homologous recombination repair, are associated with response to poly(adenosine diphosphate–ribose) polymerase (PARP) inhibition in patients with prostate and other cancers.
Vijay Rathinam: Cherishing the small victories
Authors: Stephanie Houston
Journal: The Journal of Experimental Medicine (2020)

Vijay Rathinam is an Assistant Professor of Immunology and the Director of the Graduate Program in Immunology at UConn Health. His work is focused on understanding pathogen recognition by the innate immune system, specifically how the inflammasome is activated by Gram-negative bacteria. I caught up with Vijay to find out more about his journey in science.
Escalation from ABVD Following Positive Interim Functional Imaging Improves Progression Free Survival but Not Overall Survival in Advanced Classical Hodgkin Lymphoma - a Real World Analysis
Authors: Moussab Damlaj, Mohsen Al-Zahrani, Ghulam Syed, Giamal Gmati, Tabrez Pasha, Khadega Abuelgasim, Bader Alahmari, Ayman Alhejazi, Ahmed Alaskar
Journal: Blood (2017)