tbuckley/cabot-search huggingface dataset:
Rapid, label-free detection of diffuse glioma recurrence using intraoperative stimulated Raman histology and deep neural networks
Authors: Todd C Hollon, Balaji Pandian, Esteban Urias, Akshay V Save, Arjun R Adapa, Sudharsan Srinivasan, Neil K Jairath, Zia Farooq, Tamara Marie, Wajd N Al-Holou, Karen Eddy, Jason A Heth, Siri Sahib S Khalsa, Kyle Conway, Oren Sagher, Jeffrey N Bruce, Peter Canoll, Christian W Freudiger, Sandra Camelo-Piragua, Honglak Lee, Daniel A Orringer
Journal: Neuro-Oncology (2020)

Detection of glioma recurrence remains a challenge in modern neuro-oncology. Noninvasive radiographic imaging is unable to definitively differentiate true recurrence versus pseudoprogression. Even in biopsied tissue, it can be challenging to differentiate recurrent tumor and treatment effect. We hypothesized that intraoperative stimulated Raman histology (SRH) and deep neural networks can be used to improve the intraoperative detection of glioma recurrence.We used fiber laser-based SRH, a label-free, nonconsumptive, high-resolution microscopy method (<60 sec per 1 × 1 mm2) to image a cohort of patients (n = 35) with suspected recurrent gliomas who underwent biopsy or resection. The SRH images were then used to train a convolutional neural network (CNN) and develop an inference algorithm to detect viable recurrent glioma. Following network training, the performance of the CNN was tested for diagnostic accuracy in a retrospective cohort (n = 48).Using patch-level CNN predictions, the inference algorithm returns a single Bernoulli distribution for the probability of tumor recurrence for each surgical specimen or patient. The external SRH validation dataset consisted of 48 patients (recurrent, 30; pseudoprogression, 18), and we achieved a diagnostic accuracy of 95.8%.SRH with CNN-based diagnosis can be used to improve the intraoperative detection of glioma recurrence in near-real time. Our results provide insight into how optical imaging and computer vision can be combined to augment conventional diagnostic methods and improve the quality of specimen sampling at glioma recurrence.
Rapid SARS-CoV-2 whole-genome sequencing and analysis for informed public health decision-making in the Netherlands
Authors: Bas B. Oude Munnink, David F. Nieuwenhuijse, Mart Stein, Áine O’Toole, Manon Haverkate, Madelief Mollers, Sandra K. Kamga, Claudia Schapendonk, Mark Pronk, Pascal Lexmond, Anne van der Linden, Theo Bestebroer, Irina Chestakova, Ronald J. Overmars, Stefan van Nieuwkoop, Richard Molenkamp, Annemiek A. van der Eijk, Corine GeurtsvanKessel, Harry Vennema, Adam Meijer, Andrew Rambaut, Jaap van Dissel, Reina S. Sikkema, Aura Timen, Marion Koopmans, G. J. A. P. M. Oudehuis, Janke Schinkel, Jan Kluytmans, Marjolein Kluytmans-van den Bergh, Wouter van den Bijllaardt, Robbert G. Berntvelsen, Miranda M. L. van Rijen, Peter Schneeberger, Suzan Pas, Bram M. Diederen, Anneke M. C. Bergmans, P. A. Verspui van der Eijk, Jaco J. Verweij, Anton G. N. Buiting, Roel Streefkerk, A. P. Aldenkamp, P. de Man, J. G. M. Koelemal, D. Ong, S. Paltansing, N. Veassen, Jacqueline Sleven, Leendert Bakker, Heinrich Brockhoff, Ariene Rietveld, Fred Slijkerman Megelink, James Cohen Stuart, Anne de Vries, Wil van der Reijden, A. Ros, Esther Lodder, Ellen Verspui-van der Eijk, Inge Huijskens, E. M. Kraan, M. P. M. van der Linden, S. B. Debast, N. Al Naiemi, A. C. M. Kroes, Marjolein Damen, Sander Dinant, Sybren Lekkerkerk, Oscar Pontesilli, Pieter Smit, Carla van Tienen, P. C. R. Godschalk, Jorien van Pelt, Alewijn Ott, Charlie van der Weijden, Heiman Wertheim, Janette Rahamat-Langendoen, Johan Reimerink, Rogier Bodewes, Erwin Duizer, Bas van der Veer, Chantal Reusken, Suzanne Lutgens, Peter Schneeberger, Mirjam Hermans, P. Wever, A. Leenders, Henriette ter Waarbeek, Christian Hoebe
Journal: Nature Medicine (2020)
S1PR4 ablation reduces tumor growth and improves chemotherapy via CD8+ T cell expansion
Authors: Catherine Olesch, Evelyn Sirait-Fischer, Matthias Berkefeld, Annika F. Fink, Rosa M. Susen, Birgit Ritter, Birgitta E. Michels, Dieter Steinhilber, Florian R. Greten, Rajkumar Savai, Kazuhiko Takeda, Bernhard Brüne, Andreas Weigert
Journal: Journal of Clinical Investigation (2020)

Tumor immunosuppression is a limiting factor for successful cancer therapy. The lipid sphingosine-1-phosphate (S1P), which signals through 5 distinct G protein–coupled receptors (S1PR1–5), has emerged as an important regulator of carcinogenesis. However, the utility of targeting S1P in tumors is hindered by S1P's impact on immune cell trafficking. Here, we report that ablation of the immune cell–specific receptor S1PR4, which plays a minor role in immune cell trafficking, delayed tumor development and improved therapy success in murine models of mammary and colitis-associated colorectal cancer through increased CD8+ T cell abundance. Transcriptome analysis revealed that S1PR4 affected proliferation and survival of CD8+ T cells in a cell-intrinsic manner via the expression of Pik3ap1 and Lta4h. Accordingly, PIK3AP1 expression was connected to increased CD8+ T cell proliferation and clinical parameters in human breast and colon cancer. Our data indicate a so-far-unappreciated tumor-promoting role of S1P by restricting CD8+ T cell expansion via S1PR4.
Chronic Comorbidities Among Survivors of Adolescent and Young Adult Cancer
Authors: Chun Chao, Smita Bhatia, Lanfang Xu, Kimberly L. Cannavale, F. Lennie Wong, Po-Yin Samuel Huang, Robert Cooper, Saro H. Armenian
Journal: Journal of Clinical Oncology (2020)

To describe the incidence, relative risk, and risk factors for chronic comorbidities in survivors of adolescent and young adult (AYA) cancer.This retrospective cohort study included 2-year survivors of AYA cancer diagnosed between age 15 and 39 years at Kaiser Permanente Southern California from 2000 to 2012. A comparison cohort without cancer was individually matched (13:1) to survivors of cancer on age, sex, and calendar year. Using electronic medical records, all participants were followed through December 31, 2014, for chronic comorbidity diagnoses. Poisson regression was used to evaluate the association between cancer survivor status and risk of developing each comorbidity. The associations between cumulative exposure to chemotherapy and radiation therapy and selected comorbidities were examined for survivors of cancer.The cohort included 6,778 survivors of AYA cancer and 87,737 persons without a history of cancer. The incidence rate ratio (IRR) for survivors of cancer was significantly increased for nearly all comorbidities examined. IRR ranged from 1.3 (95% CI, 1.2 to 1.4) for dyslipidemia to 8.3 (95% CI, 4.6 to 14.9) for avascular necrosis. Survivors of AYA cancer had a 2- to 3-fold increased risk for cardiomyopathy, stroke, premature ovarian failure, chronic liver disease, and renal failure. Among survivors of cancer, significant associations between chemotherapy and radiation therapy exposures and late effects of cardiomyopathy, hearing loss, stroke, thyroid disorders, and diabetes were observed from the multivariable analyses. Forty percent of survivors of AYA cancer had multiple (≥ 2) comorbidities at 10 years after index date, compared with 20% of those without cancer.Risk of developing comorbidities is increased in survivors of AYA cancer compared with the general population. Specific cancer treatment exposures were associated with risk of developing different comorbidities. These findings have important implications for survivorship care planning and patient education.
The Cytokine TGF-β Induces Interleukin-31 Expression from Dermal Dendritic Cells to Activate Sensory Neurons and Stimulate Wound Itching
Authors: Junji Xu, Peter Zanvit, Lei Hu, Pang-Yen Tseng, Na Liu, Fu Wang, Ousheng Liu, Dunfang Zhang, Wenwen Jin, Nancy Guo, Yichen Han, Jessica Yin, Alexander Cain, Mark A. Hoon, Songlin Wang, WanJun Chen
Journal: Immunity (2020)
Methods matter: pilot and feasibility studies in sports medicine
Authors: Michael J Campbell, Mohammad Ali Mansournia, Gillian Lancaster
Journal: British Journal of Sports Medicine (2020)

Do you have an idea for a large-scale, publicly funded randomised controlled trial (RCT)? Virtually all large public funding bodies now expect substantial work to have been done prior to them funding a large trial. Preliminary research suggests greater study feasibility and pilot data point to the potential for the investigators’ hypotheses to have merit. There is a new journal, Pilot and Feasibility Studies , which publishes the results of such studies. The purpose of this editorial is to encourage researchers to think about a pilot or feasibility study before the main trial and to publish the results.

Similar to a RCT, a pilot trial should have clear objectives, but in this case pertaining to feasibility and uncertainties in the main trial design, and a priori criteria for successful progression. It should be designed, conducted and reported using the same standards as any high-quality RCT. Pilot and feasibility studies are important in that they can ensure that scarce research money and researcher efforts are being invested in efficient trials that can provide definitive answers to important research questions. Guidelines for reporting pilot trials as part of an extension of the Consolidated Standards of Reporting Trials (CONSORT) statement have been published.1 2

A recent review of physical activity trials comments on some of the feasibility issues that are more common in this area.3 These include the challenge of blinding of group allocation, retaining interest of the comparison group, participant and instructor fidelity, and being able to recruit people who are not already …
Firearm Safety in an Aging United States
Authors: Erin R. Morgan, Ali Rowhani-Rahbar
Journal: JAMA Network Open (2020)

Marian E. Betz, MD, MPH; Deborah Azrael, PhD; Rachel L. Johnson, MS; Christopher E. Knoepke, PhD, MSW; Megan L. Ranney, MD, MPH; Garen J Wintemute, MD, MPH; Daniel Matlock, MD; Krithika Suresh, PhD; Matthew Miller, MD, ScD
Relatives warn of dangers of alternative treatments for cancer in BBC documentary
Authors: Clare Dyer
Journal: BMJ (2020)

Families of people who died from cancer but who might have survived had they not turned to alternative therapies have warned of the risks of shunning conventional treatments in a new BBC documentary.1

Lorna Halliday, a senior research scientist at Cambridge University, said that her mother Linda was wary of conventional medicine and concealed her breast cancer diagnosis from her daughters. She had been given “really good” survival odds if treated by a mastectomy followed by chemotherapy and radiotherapy. But she rejected NHS treatment and instead was given questionable remedies such as mistletoe injections from a range of alternative practitioners. Treated by a herbalist with the caustic ointment black salve, she died in 2014 of septicaemia after her cancer became an ulcerating tumour.

In an emotional posting on Twitter in April, after US president Donald Trump suggested trying bleach as a treatment …
Defining the signaling mechanism and relevance of H2 relaxin in prostate cancer progression
Authors: Ruth Vinall, Shangqin Liu, Hsing-Jien Kung, Ralph deVere White
Journal: Cancer Research (2007)

2658  Currently, androgen independent (AI) prostate cancer (CaP) remains incurable. The identification of novel pathways that promote androgen independent growth of prostate cancer cells is critical for the development of successful new therapies to treat CaP. Our group has identified H2 relaxin as a facilitator of androgen independent prostate cancer (AI CaP) (Vinall et al., 2006). In the current study, we demonstrate that the addition of recombinant human (rh) H2 relaxin to serum-starved LNCaP causes activation of both cAMP and PKA. cAMP activity peaked at 10 minutes following treatment with rh H2 relaxin, while PKA activity peaked at 15 minutes post-treatment. Treatment with H-89, a PKA-specific inhibitor, was able to decrease androgen-independent growth by ~20%. This result demonstrates that while the cAMP/PKA pathway partially facilitates H2 relaxin-induced androgen independent growth, other H2 relaxin stimulated signaling pathways must also play a role. ELISA and RT-PCR analysis determined that H2 relaxin was expressed in ~50% of the 60 prostate cancer patient samples analyzed to date. IHC revealed that H2 relaxin is present in both the cytoplasm and stroma of CaP patient tissue. In conclusion, this study demonstrates that the cAMP/PKA pathway plays a role in H2 relaxin-mediated AI CaP, and that H2 relaxin expression has relevance for CaP patients.
Metformin directly suppresses atherosclerosis in normoglycaemic mice via haematopoietic adenosine monophosphate-activated protein kinase
Authors: Anusha Seneviratne, Luke Cave, Gareth Hyde, Soren Kragh Moestrup, David Carling, Justin C Mason, Dorian O Haskard, Joseph James Boyle
Journal: Cardiovascular Research (2020)

Atherosclerotic vascular disease has an inflammatory pathogenesis. Heme from intraplaque haemorrhage may drive a protective and pro-resolving macrophage M2-like phenotype, Mhem, via AMPK and activating transcription factor 1 (ATF1). The antidiabetic drug metformin may also activate AMPK-dependent signalling. Hypothesis: Metformin systematically induces atheroprotective genes in macrophages via AMPK and ATF1, thereby suppresses atherogenesis.
A novel self-assembling peptide for hemostasis during endoscopic submucosal dissection: a randomized controlled trial
Authors: Sharmila Subramaniam, Kesavan Kandiah, Fergus Chedgy, Carole Fogg, Sreedhari Thayalasekaran, Asma Alkandari, Michelle Baker-Moffatt, Joanne Dash, Mark Lyons-Amos, Gaius Longcroft-Wheaton, James Brown, Pradeep Bhandari
Journal: Endoscopy (2020)

Abstract Background Endoscopic submucosal dissection (ESD) is associated with a risk of bleeding. Bleeding is usually treated with diathermy, although this does carry a risk of mucosal thermal injury. Purastat is a topical hemostat that may be effective in controlling bleeding during ESD, thereby reducing the use of heat therapy. The aim of this study was to assess the reduction in heat therapy used in the interventional group (Purastat) compared with the control group. The secondary aims were to compare the procedure length, time for hemostasis, delayed bleeding rate, adverse events, and wound healing between the groups. Methods This was a single-center randomized controlled trial of 101 patients undergoing ESD. Participants were randomized to a control group where diathermy was used to control bleeding or an interventional group where Purastat could be used. Follow-up endoscopy was performed at 4 weeks to assess wound healing. Results There was a significant reduction in the use of heat therapy for intraprocedural hemostasis in the interventional group compared with controls (49.3 % vs. 99.6 %, P &lt; 0.001). There were no significant differences in the procedure length, time for hemostasis, and delayed bleeding rate between the groups. Complete wound healing at 4 weeks was noted in 48.8 % of patients in the interventional group compared with 25.0 % of controls (P = 0.02). Conclusions This study has demonstrated that Purastat is an effective hemostat that can reduce the need for heat therapy for bleeding during ESD. It may also have a role in improving post-resection wound healing.
乾癬性関節炎を評価するための患者由来および患者報告の転帰尺度: 13カ国EULARイニシアチブ,疾患に関する乾癬性関節炎の影響(PsAID)質問票の精緻化と予備的検証
Authors: Gossec Laure, DE Wit Maarten, Kiltz Uta, Braun Juergen, Kalyoncu Umut, Scrivo Rossana, Maccarone Mara, Carton Laurence, Otsa Kati, Sooaeaer Imre, Heiberg Turid, Bertheussen Heidi, Canete Juan D, Lombarte Anselm Sanchez, Balanescu Andra, Dinte Alina, DE Vlam Kurt, Smolen Josef S, Stamm Tanja, Niedermayer Dora, Bekes Gabor, Veale Douglas, Helliwell Philip, Parkinson Andrew, Luger Thomas, Kvien Tore K
Journal: Annals of the Rheumatic Diseases (2014)
Improving nutrition and immunity with dry chain and integrated pest management food technologies in LMICs
Authors: Peetambar Dahal, Meghnath Dhimal, Krishna Belbase, Sundar Tiwari, John Groopman, Keith West, Bradley Pollock, Subodh Pyakurel, Ganga Acharya, Sunil Aryal, Yug Nath Ghimire, Manish Neupane, Rosina Poudel, Johan Van Ashbrouck, Keshavulu Kunusoth, Sarah De Saeger, Marthe De Boevre, Gokarna Gharti-Chhetri, Tek Bahadur Gurung, Kent J Bradford
Journal: The Lancet Planetary Health (2020)
Non-nucleatum <i>Fusobacterium</i> species are dominant in the Southern Chinese population with distinctive correlations to host diseases compared with <i>F. nucleatum</i>
Authors: Yan He, Prabhakar Mujagond, Wenli Tang, Wei Wu, Huimin Zheng, Xia Chen, Muxuan Chen, Wenjun Ma, Guanghui Chen, Hongwei Zhou
Journal: Gut (2020)

We read with interest the recent article by Chan et al (Gut, 2020; 0:1–10) analysing Fusobacterium diversity in the southern Chinese population.1 Fusobacterium nucleatum has been proven to be involved in the occurrence and progression of colorectal cancer (CRC); therefore, F. nucleatum has attracted more academic interest than other Fusobacterium species.2–5 Nevertheless, Chan et al ’s study made a critical observation: individuals in China (Hong Kong, Shenzhen and Zhejiang) with and without cancer harbour non-nucleatum types of Fusobacterium species as the dominating taxa. Similarly, Geva-Zatorsky et al reported that F. varium can exert a greater phenotypical impact in the host than F. nucleatum .6 Herein, we analysed the fusobacterial diversity in a Chinese population comprising 7009 individuals across 14 districts to provide a comprehensive understanding of Fusobacterium lineage distributions and their correlation with host parameters.7 8

Because the present dataset is based on 16S rRNA gene V4 sequencing, we first proved that these sequences can be …
18F-FDG PET/MRI of Rhinosporidiosis of the Upper Airways
Authors: Diego Cazzador, Diego Cecchin, Roberta Colangeli, Filippo Crimì, Enzo Emanuelli
Journal: Clinical Nuclear Medicine (2020)

Abstract A 41-year-old man from South Asia presented with a several months’ history of unilateral nasal obstruction and bleeding. At nasal endoscopy, two strawberry-like, friable, polypoid masses in the upper airways were detected. The patient’s clinical trait was compatible with an infectious disease. 18 F-FDG PET/MRI was performed to evaluate the disease extension. Two lesions occupying the nasal cavity and the nasopharynx, slightly hyperintense in T2-weighted sequences, with intense radiopharmaceutical uptake were evidenced. Endoscopic resection was performed with histopathologic diagnosis of rhinosporidiosis, a chronic granulomatous disease caused by Rhinosporidium seeberi . Although rare, rhinosporidiosis should be considered in the differential diagnoses of sinonasal hypermetabolic lesions.
Phase 1/2 Study Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of Venetoclax in Japanese Subjects with Chronic Lymphocytic Leukemia
Authors: Kiyohiko Hatake, Kazuhito Yamamoto, Noriko Fukuhara, Shigeru Kusumoto, Koji Izutsu, Ilseung Choi, Hirokazu Nagai, Hideyuki Honda, Junjiro Saeki, Andrew W. Roberts, Paulo Maciag, Suresh Agarwal, Ahmed Hamed Salem, Kevin J. Freise, Tsukasa Kiriyama, Kensei Tobinai
Journal: Blood (2017)
Myositis-specific antibodies identify a distinct interstitial pneumonia with autoimmune features phenotype
Authors: Julia Graham, Iazsmin Bauer Ventura, Chad A. Newton, Cathryn Lee, Noelle Boctor, Janelle Vu Pugashetti, Claire Cutting, Elena Joerns, Habrinder Sandhu, Jonathan H. Chung, Christine Kim Garcia, Michael Kadoch, Imre Noth, Ayodeji Adegunsoye, Mary E. Strek, Justin M. Oldham
Journal: European Respiratory Journal (2020)

Interstitial pneumonia with autoimmune features (IPAF) characterises individuals with interstitial lung disease (ILD) and features of connective tissue disease (CTD) who fail to satisfy CTD criteria. Inclusion of myositis-specific antibodies (MSAs) in the IPAF criteria has generated controversy, as these patients also meet proposed criteria for an antisynthetase syndrome. Whether MSAs and myositis-associated antibodies (MAA) identify phenotypically distinct IPAF subgroups remains unclear. A multicentre, retrospective investigation was conducted to assess clinical features and outcomes in patients meeting IPAF criteria stratified by the presence of MSAs and MAAs. IPAF subgroups were compared to cohorts of patients with idiopathic inflammatory myopathy-ILD (IIM-ILD), idiopathic pulmonary fibrosis and non-IIM CTD-ILDs. The primary end-point assessed was 3-year transplant-free survival. 269 patients met IPAF criteria, including 35 (13%) with MSAs and 65 (24.2%) with MAAs. Survival was highest among patients with IPAF-MSA and closely approximated those with IIM-ILD. Survival did not differ between IPAF-MAA and IPAF without MSA/MAA cohorts. Usual interstitial pneumonia (UIP) morphology was associated with differential outcome risk, with IPAF patients with non-UIP morphology approximating survival observed in non-IIM CTD-ILDs. MSAs, but not MAAs identified a unique IPAF phenotype characterised by clinical features and outcomes similar to IIM-ILD. UIP morphology was a strong predictor of outcome in others meeting IPAF criteria. Because IPAF is a research classification without clear treatment approach, these findings suggest that MSAs should be removed from the IPAF criteria and such patients should be managed as an IIM-ILD.
Immunization associated with primary tumor growth leads to rejection of commonly used syngeneic tumors upon tumor rechallenge
Authors: Bruno Alicke, Klara Totpal, Jill M Schartner, Amy M Berkley, Sophie M Lehar, Aude-Hélène Capietto, Rafael A Cubas, Stephen E Gould
Journal: Journal for ImmunoTherapy of Cancer (2020)

The recent success of multiple immunomodulating drugs in oncology highlights the potential of relieving immunosuppression by directly engaging the immune system in the tumor bed to target cancer cells. Durable responses to immune checkpoint inhibitors experienced by some patients may be indicative of the formation of a T cell memory response. This has prompted the search for preclinical evidence of therapy-induced long-term immunity as part of the evaluation of novel therapeutics. A common preclinical method used to document long-term immunity is the use of tumor rechallenge experiments in which tumor growth is assessed in mice that have previously rejected tumors in response to therapy. Failure of rechallenge engraftment, typically alongside successful engraftment of the same tumor in naive animals as a control, is often presented as evidence of therapy-induced tumor immunity. Here, we present evidence that formation of tumor immunity often develops independent of therapy. We observed elevated rates of rechallenge rejection following surgical resection of primary tumors for four of five commonly used models and that such postexcision immunity could be adoptively transferred to treatment-naïve mice. We also show that tumor-specific cytolytic T cells are induced on primary tumor challenge independent of therapeutic intervention. Taken together these data call into question the utility of tumor rechallenge studies and the use of naïve animals as controls to demonstrate therapy-induced formation of long-term tumor immunity.
Addition of Lomustine in the Treatment of Elderly Patients with Acute Myeloblastic Leukemia Improves Survival with Acceptably Increased Infectious Toxicity. a Filo Study
Authors: Pilar Gallego-Hernanz, Marie C Bene, Pierre-Yves Dumas, Jacques Delaunay, Caroline Bonmati, Romain Guieze, Isabelle Luquet, Pascale Cornillet-Lefebvre, Eric Delabesse, Jean-Christophe Ianotto, Mario Ojeda, Mathilde Hunault, Anne Banos, Bruno Lioure, Marc Bernard, Eric Jourdan, Norbert Vey, Hacene Zerazhi, Yosr Hicheri, Ariane C Mineur, Roselyne Delepine, Jean Yves Cahn, Norbert Ifrah, Christian Recher, Arnaud Pigneux
Journal: Blood (2017)