tbuckley/cabot-search huggingface dataset:
Topological Tumor Graphs: A Graph-Based Spatial Model to Infer Stromal Recruitment for Immunosuppression in Melanoma Histology
Authors: Henrik Failmezger, Sathya Muralidhar, Antonio Rullan, Carlos E. de Andrea, Erik Sahai, Yinyin Yuan
Journal: Cancer Research (2019)

Despite the advent of immunotherapy, metastatic melanoma represents an aggressive tumor type with a poor survival outcome. The successful application of immunotherapy requires in-depth understanding of the biological basis and immunosuppressive mechanisms within the tumor microenvironment. In this study, we conducted spatially explicit analyses of the stromal-immune interface across 400 melanoma hematoxylin and eosin (H&E) specimens from The Cancer Genome Atlas. A computational pathology pipeline (CRImage) was used to classify cells in the H&E specimen into stromal, immune, or cancer cells. The estimated proportions of these cell types were validated by independent measures of tumor purity, pathologists' estimate of lymphocyte density, imputed immune cell subtypes, and pathway analyses. Spatial interactions between these cell types were computed using a graph-based algorithm (topological tumor graphs, TTG). This approach identified two stromal features, namely stromal clustering and stromal barrier, which represented the melanoma stromal microenvironment. Tumors with increased stromal clustering and barrier were associated with reduced intratumoral lymphocyte distribution and poor overall survival independent of existing prognostic factors. To explore the genomic basis of these TTG-derived stromal phenotypes, we used a deep learning approach integrating genomic (copy number) and transcriptomic data, thereby inferring a compressed representation of copy number-driven alterations in gene expression. This integrative analysis revealed that tumors with high stromal clustering and barrier had reduced expression of pathways involved in naïve CD4 signaling, MAPK, and PI3K signaling. Taken together, our findings support the immunosuppressive role of stromal cells and T-cell exclusion within the vicinity of melanoma cells. SIGNIFICANCE: Computational histology-based stromal phenotypes within the tumor microenvironment are significantly associated with prognosis and immune exclusion in melanoma.
Primary Fascial Closure During Minimally Invasive Ventral Hernia Repair
Authors: Karla Bernardi, Oscar A. Olavarria, Mike K. Liang
Journal: JAMA Surgery (2019)

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Abstract 482: Differences in Ground Reaction Forces and Chest Compression Release Velocity in Professional and Lay Rescuers With and Without the Use of Real-Time CPR Feedback
Authors: Lyra Clark, Ben Senderling, Jeff R Gould, Chris Kaufman, Nick Stergiou
Journal: Circulation (2019)

Purpose: Chest compression release velocity (CCRV) has been associated with survival and favorable neurological outcome after cardiac resuscitation. Both complete chest release and high CCRV contribute to improved venous return during CPR. Differences in compression forces delivered by professional and lay rescuers are reported, which may contribute to differences in CCRV. The aim of this pilot study was to investigate differences in ground reaction force (GRF) and CCRV between professional and lay rescuers during CPR performed on a manikin with and without real-time feedback. Methods: Professional (n = 5) and lay rescuers (n = 11) performed two minutes of continuous compressions on a manikin positioned over a force plate for two trials. CPR feedback provided by a defibrillator was disabled in the first trial and enabled in the second. CPR pads containing an accelerometer were used to calculate individual compression characteristics. Relative maximum and minimum GRFs were calculated for each compression cycle and averaged over each trial. Paired and independent sample t tests and Pearson correlations were conducted in STATA 15.1. Results: CCRV was higher in professionals vs. lay rescuers with feedback disabled and enabled ( p &lt;0.05). Professionals had greater maximal and lower minimum forces than lay rescuers without feedback ( p &lt;0.05), though there were no differences between groups with feedback enabled (Table 1). CCRV was associated with minimum force (r = -0.63, p &lt;0.01) and force range (r = 0.78, p &lt;0.01) in all rescuers. Analysis of GRFs by CCRV for all rescuers indicated lower force minimum (9.71 + 3.16 N, p &lt;0.05) with CCRV &gt;400 mm/s in comparison to CCRV 300-400 mm/s (39.73 + 8.91 N) and CCRV 200-300 mm/s (63.82 + 16.98 N). Conclusions: CPR feedback attenuated differences in GRF between professional and lay rescuers. CCRV was greater in professionals and was associated with measures of GRF, and thus may serve as an indicator of both velocity and amount of chest release.
Mechanisms of in vivo resistance to decitabine in myelodysplatic syndromes
Authors: Samih El Ahdab, Taichun Qin, Jaroslav Jelinek, Lanlan Shen, Yasuhiro Oki, Hagop Kantarjian, Jean-Pierre Issa
Journal: Cancer Research (2007)

1634  Myelodysplastic syndromes (MDS) are malignancies of the pluripotent hematopoietic stem cells. Progression from MDS to acute myeloid leukemia (AML) is accompanied by aberrant DNA methylation of multiple genes. DNA methyltransferase inhibitors such as 5-azacytidine and 5-aza-29-deoxycytidine (decitabine, DAC)have shown efficacy in MDS patients, but resistance eventually develops in most patients. The mechanisms of resistance to DAC are unknown; possibilities include pharmacologic resistance (e.g. inactivation of deoxycytidine kinase or dCK, required for DAC incorporation into DNA), mutations in DNA methyltransferases or activation of parallel genetic pathways. To study this issue, we evaluated 8 MDS patients who had an initial complete response to DAC therapy and eventually relapsed and/or progressed to AML. The patients were 6/8 males; median age at diagnosis was 62 yr (55-79 yr); 5/8 patients had RAEB (refractory anemia with excess of blasts), 2/8 CMML (chronic myelomonocytic leukemia) and 1/8 had unclassifiable MDS/MPD. Complete remission was achieved after an average of 3 cycles (1-7 cycles). Average duration of remission was 28 weeks (11-44 weeks). In these patients, expression of dCK by quantitative PCR was not lost at resistance, and no dCK mutation was found upon direct sequencing of cDNA at relapse. We studied methylation of the 6 following genes: p15INK4b, PGRA, PGRB, C1orf102, OLIG2 and CDH13 by bisulfite pyrosequencing within the transcription start area. Using a 15% cutoff for positive methylation, an analysis of all the genes showed 18/48 (38%) positive methylation results at baseline and 10/48 samples (21%) positive methylation results at relapse. Paired t-test analysis comparing methylation levels at baseline and relapse showed no significant differences in PGRA, OLIG2, CDH13, and p15. C1orf102 was unmethylated both at baseline and at relapse. PGRB showed an average methylation decrease at relapse of 15% (range 2-32%, p=0.008). Finally, cytogenetics showed abnormalities in 3/8 patients at baseline that persisted in relapse. Two of the patients with normal baseline cytogenetics showed abnormalities at relapse: +8 and del(16)(q), respectively. Three patients continued to have normal cytogenetics at relapse. These results suggest that relapse after achieving complete remission on DAC is not associated with dCK mutations, loss of dCK expression or methylation progression. Thus, in-vivo resistance to DAC is likely mediated by activation of parallel pathways to neoplasia, such as chromosomal changes.
Human T cell response to CD1a and contact dermatitis allergens in botanical extracts and commercial skin care products
Authors: Sarah Nicolai, Marcin Wegrecki, Tan-Yun Cheng, Elvire A. Bourgeois, Rachel N. Cotton, Jacob A. Mayfield, Gwennaëlle C. Monnot, Jérôme Le Nours, Ildiko Van Rhijn, Jamie Rossjohn, D. Branch Moody, Annemieke de Jong
Journal: Science Immunology (2020)

During industrialization, humans have been exposed to increasing numbers of foreign chemicals. Failure of the immune system to tolerate drugs, cosmetics, and other skin products causes allergic contact dermatitis, a T cell-mediated disease with rising prevalence. Models of αβ T cell response emphasize T cell receptor (TCR) contact with peptide-MHC complexes, but this model cannot readily explain activation by most contact dermatitis allergens, which are nonpeptidic molecules. We tested whether CD1a, an abundant MHC I-like protein in human skin, mediates contact allergen recognition. Using CD1a-autoreactive human αβ T cell clones to screen clinically important allergens present in skin patch testing kits, we identified responses to balsam of Peru, a tree oil widely used in cosmetics and toothpaste. Additional purification identified benzyl benzoate and benzyl cinnamate as antigenic compounds within balsam of Peru. Screening of structurally related compounds revealed additional stimulants of CD1a-restricted T cells, including farnesol and coenzyme Q2. Certain general chemical features controlled response: small size, extreme hydrophobicity, and chemical constraint from rings and unsaturations. Unlike lipid antigens that protrude to form epitopes and contact TCRs, the small size of farnesol allows sequestration deeply within CD1a, where it displaces self-lipids and unmasks the CD1a surface. These studies identify molecular connections between CD1a and hypersensitivity to consumer products, defining a mechanism that could plausibly explain the many known T cell responses to oily substances.
Age distribution of human papillomavirus infection and neutralizing antibodies in healthy Chinese women aged 18–45 years enrolled in a clinical trial
Authors: L.-H. Wei, Y.-Y. Su, Y.-M. Hu, R.-C. Li, W. Chen, Q.-J. Pan, X. Zhang, F.-H. Zhao, Y.-Q. Zhao, Q. Li, Y. Hong, C. Zhao, M.-Q. Li, W.-Y. Liu, C.-H. Li, D.-P. Guo, L.-D. Ke, B.-Z. Lin, Z.-J. Lin, S. Chen, W. Sheng, Z.-Z. Zheng, S.-J. Zhuang, F.-C. Zhu, H.-R. Pan, Y.-M. Li, S.-J. Huang, J. Zhang, Y.-L. Qiao, T. Wu, N.-S. Xia
Journal: Clinical Microbiology and Infection (2020)
Агрессивные и протективные факторы желудочного сока у больных со стенозом пилородуоденальной зоны язвенного генеза
Authors: V.M. Ratchik, S.O. Tarabarov, A.I. Rudenko, N.V. Prolom
Journal: GASTROENTEROLOGY (2019)

Цель: оценить агрессивные и протективные свойства желудочного сока у больных со стенозом пилородуоденальной зоны язвенного генеза в зависимости от его степени. Материалы и методы. В отделении хирургии органов пищеварения ГУ «Институт гастроэнтерологии НАМН У­краины» за 2014–2019 годы обследовано 157 больных с различной степенью стеноза пилородуоденальной зоны язвенного генеза. Из них для изучения желудочной кислото- и слизепродукции было отобрано 92 пациента с компенсированным и субкомпенсированным стенозом, среди которых 71 мужчина, 21 женщина в возрасте от 38 до 56 лет, средний возраст (45,3 ± 5,2) года. Больные были разделены на 2 группы в зависимости от степени стеноза: 1 группа — 57 больных с компенсированным стенозом, 2 группа — 35 больных с субкомпенсированным стенозом. Контрольную группу составили 20 практически здоровых лиц. В желудочном содержимом определяли: уровень pH, концентрацию пепсина, гликопротеинов, гексозаминов, фукозы, сиаловых кислот. Результаты. Анализ изучения уровней кислото- и слизепродукции у больных со стенозом пилородуоденальной зоны различной выраженности показал, что у пациентов с субкомпенсированным стенозом отмечалось увеличение частоты гиперацидной секреции на 21,1 % (р &lt; 0,05), существенное повышение уровня пепсина (р &lt; 0,05), уменьшение концентрации общих гликопротеинов (р &lt; 0,05) (за счет существенного уменьшения концентрации фукозы и гексозаминов) по сравнению с пациентами с компенсированным стенозом, которым была более свойственна нормацидная секреция. Полученные нами данные о дисбалансе факторов агрессии и защиты желудочного содержимого позволили нам сформировать различные адаптационно-компенсаторные варианты их соотношения: 1 (гиперреактивный) — одно­временное повышение факторов агрессии и защиты; 2 (компенсаторный) — повышение уровня агрессивных факторов, нормальная концентрация защитных факторов; 3 (декомпенсаторный) — повышение уровня агрессивных факторов, снижение уровня факторов защиты. Выводы. Выявлено, что прогрессирование степени стеноза пилородуоденальной зоны язвенного генеза из компенсированного в субкомпенсированный сопровождается достоверным преобладанием факторов агрессии над факторами защиты желудочного сока и истощением функциональных возможностей слизепродуцирующего аппарата желудка. В результате выделения трех вариантов соотношения факторов агрессии и защиты желудочного сока (гиперреактивный, компенсаторный, декомпенсаторный) установлено, что декомпенсаторный вариант достоверно чаще встречается у пациентов с субкомпенсированным стенозом пилородуоденальной зоны, а значит, риск прогрессирования степени стеноза у таких больных значительно выше по сравнению с другими вариантами соотношений. Обнаруженные варианты соотношений факторов агрессии и защиты у пациентов со стенозом дают возможность дифференцированного подхода к выбору тактики лечения (мини-инвазивного эндоскопического или комбинированного эндо- и лапароскопического метода).
Safety, pharmacokinetics, and antiretroviral activity of islatravir (ISL, MK-8591), a novel nucleoside reverse transcriptase translocation inhibitor, following single-dose administration to treatment-naive adults infected with HIV-1: an open-label, phase 1b, consecutive-panel trial
Authors: Dirk Schürmann, Deanne Jackson Rudd, Saijuan Zhang, Inge De Lepeleire, Martine Robberechts, Evan Friedman, Christian Keicher, Andreas Hüser, Jörg Hofmann, Jay A Grobler, S Aubrey Stoch, Marian Iwamoto, Randolph P Matthews
Journal: The Lancet HIV (2020)
Lymphoma Recurrence Along the Lymphatic Tract on 18F-FDG PET/CT Presenting as Lower Limb Swelling
Authors: Sawsan Sabiq, Wei Ying Tham, Arvind Kumar Sinha, Hoi Yin Loi
Journal: Clinical Nuclear Medicine (2019)

Abstract A 66-year-old woman with a known history of diffuse large B-cell lymphoma presented with left lower limb swelling following recent long-distance air travel. Ultrasound Doppler showed no evidence of deep vein thrombosis. In view of her medical history, an 18 F-FDG PET/CT was ordered that found a soft tissue mass following the course of the femoral neurovascular bundle along the anteromedial aspect of the left thigh down to the popliteal fossa and the lateral calf muscle. This was confirmed to be tumor recurrence.
Three-dimensional Augmented Reality Robot-assisted Partial Nephrectomy in Case of Complex Tumours (PADUA ≥10): A New Intraoperative Tool Overcoming the Ultrasound Guidance
Authors: Francesco Porpiglia, Enrico Checcucci, Daniele Amparore, Federico Piramide, Gabriele Volpi, Stefano Granato, Paolo Verri, Matteo Manfredi, Andrea Bellin, Pietro Piazzolla, Riccardo Autorino, Ivano Morra, Cristian Fiori, Alex Mottrie
Journal: European Urology (2019)
NIMG-12. MULTICOLOURED-ASSISTED SURGERY FOR RESECTION OF HIGH GRADE GLIOMAS WITH 5-AMINOLEVULINACID
Authors: Cleopatra Charalampaki, Dimitrios Atanasopoulos
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Fluorescence guided surgery with the use of 5-aminolevulinacid (5 -ALA) is nowadays the state of the art treatment of high grade gliomas. However, intraoperative visualization of 5-ALA under dark blue light remains challenging, especially when leaking blood covers parts of the surgical field, where tumor fluorescence becomes invisible. To overcome this problem and combine the brightness of visible light with the information delivered by fluorescence we developed multispectral fluorescence, a technique able to project both information in real time to the surgeon’s eyes, and embedded it on a surgical microscope. METHODS We examined 40 patients with brain tumors who underwent surgery, using the MFL operative technique. The tumors involved comprised of 20 glioblastomas, 7 astrocytomas WHO III, 5 meningiomas and 8 metastatic tumors. The MFL technique with the real-time overlay of 5-ALA fluorescence and white light was intraoperatively compared to the classic blue filter detecting 5-ALA fluorescence. RESULTS The tumor was in all cases clearly visible and highlighted from the surrounding tissues. The pseudocolor we chose to visualize the tumor was green, representing 5-ALA fluorescence, with the surrounding brain tissueremained in its origin white color. In the cases where blood was covering the surgical field, orientation was easy to maintain, due to the additional information delivered from the white light image. CONCLUSIONS The MFL technique embedded on a surgical microscope opens the way for a precise and clear visualization of tumor 5-ALA fluorescence in real time under white light. It can be easily implemented in the resection of all tumors accumulating 5-ALA. Drawbacks of classic 5-ALA fluorescence such as hidden fluorescence because of overlying blood could be overcome with the presence of additional white light and the clear visualization of the exposed brain.
Abstract 15401: Hypertensive Diseases in Pregnancy and Renal Function Later in Life: Insights From the Genetic Epidemiology Network of Arteriopathy Study
Authors: Adebamike A Oshunbade, Seth T Lirette, Arsalan Hamid, Semiu O Gbadamosi, Olusola Orimoloye, Martin Tibuakuu, Daisuke Kamimura, Donald Clark, Wondwosen K Yimer, Stephen D Grado, Elizabeth A Lutz, Robert J Mentz, Ervin R Fox, Javed Butler, Kenneth R Butler, Thomas H MosleyJr, Michael E Hall
Journal: Circulation (2019)

Background: Hypertension in pregnancy has been associated with increased risk for albuminuria in the future. However, there are limited data assessing the relationship between hypertensive diseases...
Cutting out the middleman: Separating attributional biases from memory deficits
Authors: Wei-Chun Wang
Journal: Behavioral and Brain Sciences (2019)

Bastin and colleagues present an integrative model of how recollection- and familiarity-based memories are represented in the brain. While they emphasize the role of attribution mechanisms in shaping memory retrieval, prior work examining implicit memory suggests that memory deficits may be better understood by separating attributional biases from the underlying memory traces.
Evaluation of the Functional Effects of an African American Glucose-6-Phosphate Dehydrogenase (G6PD) Polymorphism (Val68Met) on RBC Hemolytic Propensity and Post-Transfusion Recovery in a Humanized Mouse Model
Authors: Ling Wang, Benjamin Zuchelkowski, Derek Sinchar, Minying Yang, Sebastien Gingras, Tamir Kanias, Janet S Lee, Daniel Kim-Shapiro, Grier Page, Mark T Gladwin
Journal: Blood (2019)
A study of dupilumab in the treatment of adolescents with eczema
Authors: M.J. Cork, D. Thaçi, L.F. Eichenfield, P.D. Arkwright, T. Hultsch, J.D. Davis, Y. Zhang, X. Zhu, Z. Chen, M. Li, M. Ardeleanu, A. Teper, B. Akinlade, A. Gadkari, L. Eckert, M.A. Kamal, M. Ruddy, N.M.H. Graham, G. Pirozzi, N. Stahl, A.T. DiCioccio, A. Bansal
Journal: British Journal of Dermatology (2020)

Atopic dermatitis (AD), also known as eczema, is characterized by red, oozy, and dry skin that can become cracked and infected. Intense itching, which can be very troublesome and can cause sleep disturbance, is the main complaint of patients with AD. AD often begins in childhood and affects 1 in 4 teenagers worldwide. For teenagers, the itchiness and appearance of AD skin can significantly reduce quality of life, but there are few effective treatment options for moderate‐to‐severe AD that are suitable for long‐term use. Dupilumab is a new drug that blocks key molecules that cause allergic conditions, such as AD. It has been shown to be effective in treating moderate‐to‐severe AD in adults and to be relatively safe for long‐term use. This study was conducted in multiple centres across Europe and Canada in 40 patients aged 12 to 17 who received treatment with dupilumab for up to a year. The researchers wanted to know whether dupilumab is effective and safe for treating AD with long‐term use in these patients. They also wanted to know how dupilumab is processed by the body in patients with AD in this age group. They found that treatment with dupilumab substantially improves the skin and symptoms of AD, including itching, in these younger patients, without causing any unexpected side effects. They also found that dupilumab is processed the same way in these younger patients as in adults. The improvements were maintained throughout the one year of treatment. The study results support the use of dupilumab in the continuous treatment of adolescents with moderate‐to‐severe AD. This summary relates to the study: Dupilumab in adolescents with uncontrolled moderate‐to‐severe atopic dermatitis: results from a phase IIa open‐label trial and subsequent phase III open‐label extension
Nanoparticle cancer vaccines: Design considerations and recent advances
Authors: Jingjing Liu, Lei Miao, Jiying Sui, Yanyun Hao, Guihua Huang
Journal: Asian Journal of Pharmaceutical Sciences (2019)

Vaccines therapeutics manipulate host's immune system and have broad potential for cancer prevention and treatment. However, due to poor immunogenicity and limited safety, fewer cancer vaccines have been successful in clinical trials. Over the past decades, nanotechnology has been exploited to deliver cancer vaccines, eliciting long-lasting and effective immune responses. Compared to traditional vaccines, cancer vaccines delivered by nanomaterials can be tuned towards desired immune profiles by (1) optimizing the physicochemical properties of the nanomaterial carriers, (2) modifying the nanomaterials with targeting molecules, or (3) co-encapsulating with immunostimulators. In order to develop vaccines with desired immunogenicity, a thorough understanding of parameters that affect immune responses is required. Herein, we discussed the effects of physicochemical properties on antigen presentation and immune response, including but not limited to size, particle rigidity, intrinsic immunogenicity. Furthermore, we provided a detailed overview of recent preclinical and clinical advances in nanotechnology for cancer vaccines, and considerations for future directions in advancing the vaccine platform to widespread anti-cancer applications.
Understanding misidentification syndromes using the integrative memory model
Authors: Joel Patchitt, Sukhi S. Shergill
Journal: Behavioral and Brain Sciences (2019)

Abstract Misidentification syndromes occur commonly in neuropsychiatric practice and can be explained through aberrant integration of recollection and familiarity, in keeping with a dysfunction at the level of the attributional system in the new integrative memory model. We examine neuroimaging findings associated with Fregoli and Capgras syndromes and compare these with the proposed neural substrate of the integrative memory model supporting the core and attribution functions.