tbuckley/cabot-search huggingface dataset:
AI-Assisted <i>In Situ</i> Detection of Human Glioma Infiltration Using a Novel Computational Method for Optical Coherence Tomography
Authors: Ronald M. Juarez-Chambi, Carmen Kut, Jose J. Rico-Jimenez, Kaisorn L. Chaichana, Jiefeng Xi, Daniel U. Campos-Delgado, Fausto J. Rodriguez, Alfredo Quinones-Hinojosa, Xingde Li, Javier A. Jo
Journal: Clinical Cancer Research (2019)

Abstract Purpose: In glioma surgery, it is critical to maximize tumor resection without compromising adjacent noncancerous brain tissue. Optical coherence tomography (OCT) is a noninvasive, label-free, real-time, high-resolution imaging modality that has been explored for glioma infiltration detection. Here, we report a novel artificial intelligence (AI)-assisted method for automated, real-time, in situ detection of glioma infiltration at high spatial resolution. Experimental Design: Volumetric OCT datasets were intraoperatively obtained from resected brain tissue specimens of 21 patients with glioma tumors of different stages and labeled as either noncancerous or glioma-infiltrated on the basis of histopathology evaluation of the tissue specimens (gold standard). Labeled OCT images from 12 patients were used as the training dataset to develop the AI-assisted OCT-based method for automated detection of glioma-infiltrated brain tissue. Unlabeled OCT images from the other 9 patients were used as the validation dataset to quantify the method detection performance. Results: Our method achieved excellent levels of sensitivity (∼100%) and specificity (∼85%) for detecting glioma-infiltrated tissue with high spatial resolution (16 μm laterally) and processing speed (∼100,020 OCT A-lines/second). Conclusions: Previous methods for OCT-based detection of glioma-infiltrated brain tissue rely on estimating the tissue optical attenuation coefficient from the OCT signal, which requires sacrificing spatial resolution to increase signal quality, and performing systematic calibration procedures using tissue phantoms. By overcoming these major challenges, our AI-assisted method will enable implementing practical OCT-guided surgical tools for continuous, real-time, and accurate intraoperative detection of glioma-infiltrated brain tissue, facilitating maximal glioma resection and superior surgical outcomes for patients with glioma.
Same meat, different gravy: ignore the new names of mycobacteria
Authors: Enrico Tortoli, Barbara A. Brown-Elliott, James D. Chalmers, Daniela M. Cirillo, Charles L. Daley, Stefan Emler, R. Andres Floto, Maria J. Garcia, Wouter Hoefsloot, Won-Jung Koh, Christoph Lange, Michael Loebinger, Florian P. Maurer, Kozo Morimoto, Stefan Niemann, Elvira Richter, Christine Y. Turenne, Ravikiran Vasireddy, Sruthi Vasireddy, Dirk Wagner, Richard J. Wallace, Nancy Wengenack, Jakko van Ingen
Journal: European Respiratory Journal (2019)

<b>A new name for most <i>Mycobacterium</i> species has been recently proposed. According to taxonomic rules novel and previous nomenclature coexist and are synonyms. The use of the latter has the advantage of avoiding confusion for healthcare and harm for patients.</b>http://bit.ly/2XhTACc
A Novel Role for IL-6 Receptor Classic Signaling: Induction of RORγt+Foxp3+ Tregs with Enhanced Suppressive Capacity
Authors: Julia Hagenstein, Simon Melderis, Anna Nosko, Matthias T. Warkotsch, Johannes V. Richter, Torben Ramcke, Georg R. Herrnstadt, Jürgen Scheller, Isabell Yan, Hans-Willi Mittrücker, Malte A. Kluger, Oliver M. Steinmetz
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement The pleiotropic cytokine IL-6 has commonly been regarded as the master switch of inflammation because it augments proinflammatory T helper 17 cell (Th17) responses and suppresses anti-inflammatory regulatory T cells (Tregs). This study challenges this paradigm. Studies in mice show that IL-6 receptor classic signaling effectively induces Th17 responses but also, in contrast to the previous concept, increases Treg activation. Engagement of the IL-6 receptor results in the generation of a unique ROR γ t-expressing Treg subtype with enhanced suppressive capacity. Expansion of this highly activated, IL-6–dependent effector Treg population is associated with a significantly improved outcome of experimental acute GN. These results shed new light on IL-6 biology and help to establish IL-6 directed therapies for GN. Background New therapies blocking the IL-6 receptor (IL-6R) have recently become available and are successfully being used to treat inflammatory diseases like arthritis. Whether IL-6 blockers may help patients with kidney inflammation currently remains unknown. Methods To learn more about the complex role of CD4 + T cell-intrinsic IL-6R signaling, we induced nephrotoxic nephritis, a mouse model for crescentic GN, in mice lacking T cell–specific IL-6Ra. We used adoptive transfer experiments and studies in reporter mice to analyze immune responses and Treg subpopulations. Results Lack of IL-6Ra signaling in mouse CD4 + T cells impaired the generation of proinflammatory Th17 cells, but surprisingly did not ameliorate the course of GN. In contrast, renal damage was significantly reduced by restricting IL-6Ra deficiency to T effector cells and excluding Tregs. Detailed studies of Tregs revealed unaltered IL-10 production despite IL-6Ra deficiency. However, in vivo and in vitro , IL-6Ra classic signaling induced RORγt + Foxp3 + double-positive Tregs (biTregs), which carry the trafficking receptor CCR6 and have potent immunoregulatory properties. Indeed, lack of IL-6Ra significantly reduced Treg in vitro suppressive capacity. Finally, adoptive transfer of T cells containing IL-6Ra −/− Tregs resulted in severe aggravation of GN in mice. Conclusions Our data refine the old paradigm, that IL-6 enhances Th17 responses and suppresses Tregs. We here provide evidence that T cell–intrinsic IL-6Ra classic signaling indeed induces the generation of Th17 cells but at the same time highly immunosuppressive RORγt + biTregs. These results advocate caution and indicate that IL-6–directed therapies for GN need to be cell-type specific.
The endometrial immune environment of women with endometriosis
Authors: Júlia Vallvé-Juanico, Sahar Houshdaran, Linda C Giudice
Journal: Human Reproduction Update (2019)

Abstract BACKGROUND Endometriosis, a common oestrogen-dependent inflammatory disorder in women of reproductive age, is characterized by endometrial-like tissue outside its normal location in the uterus, which causes pelvic scarring, pain and infertility. While its pathogenesis is poorly understood, the immune system (systemically and locally in endometrium, pelvic endometriotic lesions and peritoneal fluid) is believed to play a central role in its aetiology, pathophysiology and associated morbidities of pain, infertility and poor pregnancy outcomes. However, immune cell populations within the endometrium of women with the disease have had incomplete phenotyping, thereby limiting insight into their roles in this disorder. OBJECTIVE AND RATIONALE The objective herein was to determine reproducible and consistent findings regarding specific immune cell populations and their abundance, steroid hormone responsiveness, functionality, activation states, and markers, locally and systemically in women with and without endometriosis. SEARCH METHODS A comprehensive English language PubMed, Medline and Google Scholar search was conducted with key search terms that included endometriosis, inflammation, human eutopic/ectopic endometrium, immune cells, immune population, immune system, macrophages, dendritic cells (DC), natural killer cells, mast cells, eosinophils, neutrophils, B cells and T cells. OUTCOMES In women with endometriosis compared to those without endometriosis, some endometrial immune cells display similar cycle-phase variation, whereas macrophages (Mø), immature DC and regulatory T cells behave differently. A pro-inflammatory Mø1 phenotype versus anti-inflammatory Mø2 phenotype predominates and natural killer cells display abnormal activity in endometrium of women with the disease. Conflicting data largely derive from small studies, variably defined hormonal milieu and different experimental approaches and technologies. WIDER IMPLICATIONS Phenotyping immune cell subtypes is essential to determine the role of the endometrial immune niche in pregnancy and endometrial homeostasis normally and in women with poor reproductive history and can facilitate development of innovative diagnostics and therapeutics for associated symptoms and compromised reproductive outcomes.
Abstract 17936: Carvedilol Suppresses ST Segment Elevation in A-Kinase Anchoring Protein 150 Knockout Mice: Its Novel Therapeutic Role in Coronary Spastic Angina
Authors: Noritomo Narita, Kenji Hanada, Hiroaki Ichikawa, Yoshihiro Kimura, Maiko Senoo, Masato Narita, Manabu Yonekura, Makoto Tanaka, Tomohiro Osanai, Ken Okumura, Hirofumi Tomita
Journal: Circulation (2017)

Introduction: We previously reported that enhanced phospholipase C (PLC) activity plays a key role in the pathogenesis of coronary spastic angina and increased intracellular calcium concentration (...
In situ polymerization on nanoscale metal-organic frameworks for enhanced physiological stability and stimulus-responsive intracellular drug delivery
Authors: Yuan Liu, Christina S. Gong, Yunlu Dai, Zhen Yang, Guocan Yu, Yijing Liu, Mingru Zhang, Lisen Lin, Wei Tang, Zijian Zhou, Guizhi Zhu, Jiji Chen, Orit Jacobson, Dale O. Kiesewetter, Zhantong Wang, Xiaoyuan Chen
Journal: Biomaterials (2019)
Effect of dosing cycles on safety of denileukin diftitox (Dd) in cutaneous T-cell lymphoma (CTCL) patients: Integrated analysis of three phase III studies
Authors: Y. Kim, J. Beynon
Journal: Journal of Clinical Oncology (2009)

e19557 Background: Dd is a novel IL-2 receptor-targeted recombinant fusion protein that is approved for treatment of persistent/recurrent CTCL expressing CD25. To date, Dd is the most extensively studied agent in CTCL. The safety of Dd was assessed with respect to dosing cycle in CTCL subjects in 3 large phase III studies: 93–04–10 (study 10), L4389–11 (study 11) and L4389–14 (study 14). Methods: Subjects received Dd doses of 9 or 18 mcg/kg IV daily for 5 days, repeating every 21 days for up to 8 cycles; study 11 also included a placebo arm. Subjects in studies 10 and 11 were CD25(+); study 14 also included CD25(-) subjects. Safety data from these studies were integrated and are presented by dosing cycle. Results: Table 1 shows a summary of all reported adverse events (AEs) by cycle for the 3 studies. For subjects completing at least 4 cycles of Dd treatment the incidence of any AEs was lower in the 3rd and 4th cycles as compared to the 1st and 2nd cycles and the incidence of AEs continued to decrease after cycle 4. Conclusions: In the studies analyzed, the incidence of AEs decreased with each subsequent treatment cycle for subjects receiving Dd. [Table: see text] [Table: see text]
Phase II multi-center study of ruxolitinib phosphate for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL).
Authors: Avyakta Kallam, Thomas E. Witzig, Mark J. Roschewski, Elizabeth Lyden, Matthew Alexander Lunning, Philip Jay Bierman, Gregory Bociek, James O. Armitage, Julie Vose
Journal: Journal of Clinical Oncology (2019)

e19063 Background: Constitutive activation of the JAK-STAT pathway has been reported in lymphomas, suggesting that targeting this pathway could show clinical benefit. Ruxolitinib phosphate, an oral JAK inhibitor represents a potential therapeutic agent for high grade lymphomas. This study is designed to investigate benefits of ruxolitinib in patients with relapsed or refractory PTCL and DLBCL Methods: Patients with relapsed/refractory DLBCL and aggressive T cell lymphomas who were ineligible for, or relapsed after, stem cell transplantation were eligible. Patients received ruxolitinib, at a dose of 10mg or 5mg BID, with gradual escalation to 25mg BID. Weekly hematological assessments were done during the first cycle, CT scans were done after every two cycles. Descriptive statistics for response to therapy were collected. Progression free survival (PFS), Overall survival (OS) curves were plotted using Kaplan-Meier method, comparisons between groups were made using the log rank test. Primary outcome of the study was to assess the overall response rate (ORR). Secondary objectives were to determine PFS, OS, duration of response and safety. Relationship between responses to oral ruxolitnib and gene expression profiling was explored. Results: Of the 60 patients enrolled, 25 patients had PTCL, 32 DLBCL, 3 pending path review. Median age was 62 yrs., 56.6% had stage IV disease. Median number of cycles received was 2 (min 1, max 60). At the time of evaluation, 76% patients had progressed on therapy. The median follow-up of patients was 3.7 months (min 0.9; max 61.4). Data for 41 patients was available for evaluation of response. Complete response (CR) was noted in 1 patient with PTCL. Partial response (PR) was noted in 1, stable disease (SD) in 4 patients. Among the responders, a PTCL patient with SD had a sustained response for 60 months, a patient with PR had a response duration of 31 months. The median OS and PFS were 5.9 and 1.8 months. PFS was 2.2 months in patients with PTCL and 1.8 months in DLBCL. Median OS was 5 months in patients with DLBCL, 6.9 months in PTCL. The estimated 6 month PFS and OS were 17% (95%CI: 9%, 28%) , 49% (95%CI: 35%, 62%). There was no difference in PFS or OS between PTCL and DLBCL (p = 0.42, p = 0.94). Grade 3 or higher adverse events were seen in 62%. Anemia was seen in 20%, thrombocytopenia in 8%, infections in 6%. Conclusions: Ruxolitinib can produce responses in some patients with relapsed/refractory NHL, particularly in patients with PTCL. It may play a role in combination therapies in future. Clinical trial information: NCT01431209.
Tracking Impact of Interstitial Lung Disease in Systemic Sclerosis in a Complete Nationwide Cohort
Authors: Anna-Maria Hoffmann-Vold, Håvard Fretheim, Anne-Kristine Halse, Marit Seip, Helle Bitter, Marianne Wallenius, Torhild Garen, Anne Salberg, Cathrine Brunborg, Øyvind Midtvedt, May Brit Lund, Trond M. Aaløkken, Øyvind Molberg
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Interstitial lung disease (ILD) represents a major challenge in systemic sclerosis (SSc), but there are no precise, population-based data on its overall impact, limiting opportunities for screening and management strategies.Objectives: Evaluate impact of ILD in a unique, nationwide, population-based SSc cohort.Methods: ILD was assessed prospectively in the Norwegian SSc (Nor-SSc) cohort, including all 815 patients with SSc resident in the country from 2000 to 2012. Lung high-resolution computed tomography (HRCT) scans were available for fibrosis quantification at baseline (n = 650, 80%) and follow-up. Pulmonary function tests were assessed at baseline (n = 703, 86%) and follow-up. Vital status and standardized mortality ratios (SMRs) were estimated at study end (2018) in the 630 incident Nor-SSc cases and 15 individually matched control subjects. Cumulative survival rates were computed.Measurements and Main Results: At baseline, 50% of the subjects with SSc (n = 324) had ILD by HRCT and 46% displayed pulmonary function declines consistent with ILD progression. Mortality correlated with extent of lung fibrosis as SMR increased from 2.2 with no fibrosis to 8.0 with greater than 25% fibrosis. SMR was inversely related to baseline FVC% and increased at all FVC levels below 100%. In patients with normal-range baseline FVC (80–100%), the 5- and 10-year survival rates correlated with presence or absence of lung fibrosis, being 83% and 80%, respectively, with no fibrosis and 69% and 56%, respectively, with lung fibrosis (P = 0.03).Conclusions: The mere presence of ILD at baseline appears to affect outcome in SSc, suggesting that all patients with SSc should undergo a baseline pulmonary function test and lung HRCT screening to diagnose ILD early and tailor further management.
Central serous chorioretinopathy: Towards an evidence-based treatment guideline
Authors: Thomas J. van Rijssen, Elon H.C. van Dijk, Suzanne Yzer, Kyoko Ohno-Matsui, Jan E.E. Keunen, Reinier O. Schlingemann, Sobha Sivaprasad, Giuseppe Querques, Susan M. Downes, Sascha Fauser, Carel B. Hoyng, Felice Cardillo Piccolino, Jay K. Chhablani, Timothy Y.Y. Lai, Andrew J. Lotery, Michael Larsen, Frank G. Holz, K. Bailey Freund, Lawrence A. Yannuzzi, Camiel J.F. Boon
Journal: Progress in Retinal and Eye Research (2019)

Central serous chorioretinopathy (CSC) is a common cause of central vision loss, primarily affecting men 20–60 years of age. To date, no consensus has been reached regarding the classification of CSC, and a wide variety of interventions have been proposed, reflecting the controversy associated with treating this disease. The recent publication of appropriately powered randomised controlled trials such as the PLACE trial, as well as large retrospective, non-randomised treatment studies regarding the treatment of CSC suggest the feasibility of a more evidence-based approach when considering treatment options. The aim of this review is to provide a comprehensive overview of the current rationale and evidence with respect to the variety of interventions available for treating CSC, including pharmacology, laser treatment, and photodynamic therapy. In addition, we describe the complexity of CSC, the challenges associated with treating CSC, and currently ongoing studies. Many treatment strategies such as photodynamic therapy using verteporfin, oral mineralocorticoid antagonists, and micropulse laser treatment have been reported as being effective. Currently, however, the available evidence suggests that half-dose (or half-fluence) photodynamic therapy should be the treatment of choice in chronic CSC, whereas observation may be the preferred approach in acute CSC. Nevertheless, exceptions can be considered based upon patient-specific characteristics.
Interactions Between Influenza and Heart Failure Hospitalizations—Diagnostic and Pathogenetic Issues
Authors: Saifei Liu, John D. Horowitz
Journal: JAMA Cardiology (2019)

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Clinical safety of tbo-filgrastim in chemotherapy-induced neutropenia: Integrated analysis of the phase III studies.
Authors: Andreas Engert, Anton Buchner, Udo W. Mueller, Peter Bias
Journal: Journal of Clinical Oncology (2013)

e13552 Background: Tbo-filgrastim is a granulocyte colony-stimulating factor (G-CSF) approved for use in the US as a biologic under BLA 351(a) for reducing duration of severe neutropenia in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy (CTx) associated with a clinically significant incidence of febrile neutropenia. Here, we report an integrated analysis of clinical safety data from three Phase III studies. Methods: Safety results from three Phase III studies in breast cancer (placebo-controlled), non-small cell lung cancer, and non-Hodgkin lymphoma were integrated. All safety variables were analyzed using descriptive statistics. The incidence of treatment-emergent adverse events (TEAEs) was compared between treatment groups using Fisher's exact test (2-sided P-values). Changes in laboratory parameters from baseline were compared between the tbo-filgrastim and filgrastim treatment groups using the Wilcoxon test. Results: In the integrated analysis of CTx Cycle 1, 80.2% of 677 patients experienced a TEAE; 16.7% of these were related to study drug. The most commonly reported TEAEs were nausea, alopecia, neutropenia, diarrhea, asthenia, and vomiting, and most due to concomitant CTx. The most commonly reported drug-related TEAEs were bone pain (3.4%), diarrhea (2.2%), asthenia (2.2%), myalgia (1.9%), arthralgia (1.5%), headache (1.2%), and pyrexia (1.0%), all of which are characteristic of G-CSFs. Five patients had serious drug-related TEAEs; none caused reductions in the dose of study drug or scheduled CTx. There were 11 deaths across studies; none was considered drug related. There were no clinically significant differences between tbo-filgrastim and filgrastim in the overall incidence of deaths, serious or severe TEAEs, discontinuations due to TEAEs, or in laboratory safety variables. In all cycles of CTx, the most commonly reported TEAEs in patients treated with tbo-filgrastim correlated with those of the reference filgrastim. Conclusions: Tbo-filgrastim is safe and well tolerated in breast cancer, non-small cell lung cancer, and non-Hodgkin lymphoma patients undergoing CTx, with a safety profile similar to that of the reference filgrastim. Clinical trial information: 2004-001452-36, 2004-001450-84, 2004-001449-13.
“Edinburgh Seven” are granted degrees 150 years after their studies
Authors: Alison Shepherd
Journal: BMJ (2019)

Seven current medical students at Edinburgh University accepted degree certificates on behalf of the pioneering women who were among the first female students to be admitted to a British university (fig 1).



Fig 1 
Pictured left to right are Violet Borkowska, Hikari Sakurai, Megan Cameron, Simran Piya, Izzie Dighero, Caitlin Taylor, and Mei …