tbuckley/cabot-search huggingface dataset:
Dual‐Controlled Release of Icariin/Mg<sup>2+</sup> from Biodegradable Microspheres and Their Synergistic Upregulation Effect on Bone Regeneration
Authors: Zuoying Yuan, Zhuo Wan, Pengfei Wei, Xin Lu, Jianping Mao, Qing Cai, Xu Zhang, Xiaoping Yang
Journal: Advanced Healthcare Materials (2020)

Abstract Current scaffolds applied for bone tissue engineering are still lacking sufficient osteogenic capacity to induce efficient bone regeneration. Biodegradable microsphere‐type scaffolds are designed to achieve the dual‐controlled release of a Chinese medicine (i.e., icariin, ICA) and a bioactive ion (i.e., Mg 2+ ), in order to achieve their synergistic effect on inducing osteogenesis. The hydrophobic icariin is preloaded onto MgO/MgCO 3 (1:1 in weight ratio) particles at different amounts and then the particles are encapsulated into biodegradable poly(lactide‐ co ‐glycolide) (PLGA) microspheres (PMI) at a fixed fraction (20 wt%). Continuous releases of Mg 2+ ion and icariin from the microspheres are detected, showing dependence on icariin amounts. At an optimized moderate loading amount, the resulting PMI‐M microspheres display the strongest activation effect on cell biological behaviors among all the designs. By implanting the PMI‐M microspheres into rat calvarial defects for 16 weeks, it is found that they can effectively enhance new bone formation, presenting significantly higher capacity in inducing osteogenesis than PMg (containing MgO/MgCO 3 but without icariin) and blank PLGA microspheres. Clearly, the released Mg 2+ ions are beneficial to osteogenesis, and the coincorporation of icariin exerts supplemental effects in inducing new bone formation, which suggest a promising strategy to regenerate severe bone injuries by designing a dual‐release system.
Positive rectal swabs in young patients recovered from coronavirus disease 2019 (COVID-19)
Authors: Bin Zhang, Shuyi Liu, Yuhao Dong, Lu Zhang, Qingyang Zhong, Yujian Zou, Shuixing Zhang
Journal: Journal of Infection (2020)

To investigate the widely concerned issue about positive real-time reverse transcription polymerase chain reaction (RT-PCR) test results after discharge in patients recovered from coronavirus disease 2019 (COVID-19).We identified seven cases of COVID-19 who was readmitted to hospital because of positive RT-PCR after discharge, including three pediatrics and four young adult patients.Six patients had positive rectal swabs but negative throat swabs, and one patient had positive throat swabs. All the patients continued to be asymptomatic and had unchanged chest computed tomography from previous images. The time from hospital discharge to positive RT-PCR after recovery was 7-11 days. The time from positive to negative rectal swabs was 5-23 days.The study might suggest the positive RT-PCR after recovery did not mean disease relapse or virus reinfection. Adding RT-PCR test of rectal swabs to the criteria for discharge or discontinuation of quarantine might be necessary.
Focal Scleral Nodule
Authors: Adrian T. Fung, Sebastian M. Waldstein, Orly Gal-Or, Marco Pellegrini, Chiara Preziosa, Jerry A. Shields, R. Joel Welch, Rosa Dolz-Marco, David Sarraf, Aaron Nagiel, Robert Lalane, Jesse J. Jung, Nicola G. Ghazi, Prithvi Ramtohul, Jennifer J. Arnold, Yoichi Sakurada, Netan Choudhry, Chandrakumar Balaratnasingam, K. Bailey Freund, Carol L. Shields
Journal: Ophthalmology (2020)
EPIGENOME ALTERATIONS DEFINE LETHAL CIMP POSITIVE EPENDYMOMAS OF INFANCY
Authors: M. D. Taylor, S. Mack, H. Witt, P. Dirks, S. Pfister, A. Korshunov
Journal: Neuro-Oncology (2014)

BACKGROUND: Ependymomas are common childhood brain tumors that occur throughout the nervous system, but are most common in the pediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. METHODS: We undertook genetic, and epigenetic studies of a series of childhood posterior fossa ependymomas. RESULTS: Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic SNVs. While devoid of recurrent SNVs and focal copy number aberrations, poor prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype (CIMP). Transcriptional silencing driven by CpG methylation converges exclusively on targets of the polycomb repressor complex 2 (PRC2) that represses expression of differentiation genes through tri-methylation of H3K27. CIMP-positive (CIMP+) hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. CONCLUSIONS: We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically de-regulated but genetically bland. SECONDARY CATEGORY: n/a.
Rosai-Dorfman Disease—Utility of 18F-FDG PET/CT for Initial Evaluation and Follow-up
Authors: Sonia Mahajan, Reiko Nakajima, Mariko Yabe, Ahmet Dogan, Gary A. Ulaner, Joachim Yahalom, Ariela Noy, Eli L. Diamond, Heiko Schöder
Journal: Clinical Nuclear Medicine (2020)

Background The role of imaging in the management of Rosai-Dorfman disease (RDD), a rare non-Langerhans cell histiocytosis, is not clearly defined. We present an analysis of FDG PET/CT findings obtained for initial disease characterization, follow-up evaluation, and treatment planning for this disease. Methods From an institutional pathology database (2001–2018), we identified RDD patients who underwent FDG PET/CT scans either as part of clinical care or when done as part of clinical trials. For all scans, sites of abnormal FDG uptake were assessed, and SUVmax was measured. Comparison of PET/CT findings was made with anatomic (CT/MRI-based) imaging, where available. Instances of changing treatment based on PET/CT were recorded. Results We reviewed 109 FDG PET/CT scans in 27 patients with RDD. Five of 27 patients had only nodal/cutaneous disease, whereas 22 patients had extranodal disease, most commonly in bone (n = 9) and central nervous system (n = 7). PET/CT identified sites of active disease in 24 of 27 patients. All identified bone and extraskeletal lesions, except for a brain lesion in 1 patient, were FDG-avid. In 6 of 20 patients (30%) with available prior CT or MRI, PET/CT demonstrated additional RDD lesions (bones: n = 5, pleura: n = 1) that were not apparent on anatomic imaging; 3 of these lesions were outside the CT field of view, and 3 were not recognized on CT. Overall, 13 of 109 PET/CT scans led to a change in management, affecting 41% (11/27) of patients. Conclusion FDG PET/CT was valuable in defining disease extent and optimizing treatment strategy in patients with RDD.
Evaluation of a Deep Neural Network for Automated Classification of Colorectal Polyps on Histopathologic Slides
Authors: Jason W. Wei, Arief A. Suriawinata, Louis J. Vaickus, Bing Ren, Xiaoying Liu, Mikhail Lisovsky, Naofumi Tomita, Behnaz Abdollahi, Adam S. Kim, Dale C. Snover, John A. Baron, Elizabeth L. Barry, Saeed Hassanpour
Journal: JAMA Network Open (2020)

Histologic classification of colorectal polyps plays a critical role in screening for colorectal cancer and care of affected patients. An accurate and automated algorithm for the classification of colorectal polyps on digitized histopathologic slides could benefit practitioners and patients.To evaluate the performance and generalizability of a deep neural network for colorectal polyp classification on histopathologic slide images using a multi-institutional data set.This prognostic study used histopathologic slides collected from January 1, 2016, to June 31, 2016, from Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, with 326 slides used for training, 157 slides for an internal data set, and 25 for a validation set. For the external data set, 238 slides for 179 distinct patients were obtained from 24 institutions across 13 US states. Data analysis was performed from April 9 to November 23, 2019.Accuracy, sensitivity, and specificity of the model to classify 4 major colorectal polyp types: tubular adenoma, tubulovillous or villous adenoma, hyperplastic polyp, and sessile serrated adenoma. Performance was compared with that of local pathologists' at the point of care identified from corresponding pathology laboratories.For the internal evaluation on the 157 slides with ground truth labels from 5 pathologists, the deep neural network had a mean accuracy of 93.5% (95% CI, 89.6%-97.4%) compared with local pathologists' accuracy of 91.4% (95% CI, 87.0%-95.8%). On the external test set of 238 slides with ground truth labels from 5 pathologists, the deep neural network achieved an accuracy of 87.0% (95% CI, 82.7%-91.3%), which was comparable with local pathologists' accuracy of 86.6% (95% CI, 82.3%-90.9%).The findings suggest that this model may assist pathologists by improving the diagnostic efficiency, reproducibility, and accuracy of colorectal cancer screenings.
A high definition picture of somatic mutations in chronic lymphoproliferative disorder of natural killer cells
Authors: Vanessa Rebecca Gasparini, Andrea Binatti, Alessandro Coppe, Antonella Teramo, Cristina Vicenzetto, Giulia Calabretto, Gregorio Barilà, Annica Barizza, Edoardo Giussani, Monica Facco, Satu Mustjoki, Gianpietro Semenzato, Renato Zambello, Stefania Bortoluzzi
Journal: Blood Cancer Journal (2020)

Abstract The molecular pathogenesis of chronic lymphoproliferative disorder of natural killer (NK) cells (CLPD‐NK) is poorly understood. Following the screening of 57 CLPD-NK patients, only five presented STAT3 mutations. WES profiling of 13 cases negative for STAT3/STAT5B mutations uncovered an average of 18 clonal, population rare and deleterious somatic variants per patient. The mutational landscape of CLPD-NK showed that most patients carry a heavy mutational burden, with major and subclonal deleterious mutations co-existing in the leukemic clone. Somatic mutations hit genes wired to cancer proliferation, survival, and migration pathways, in the first place Ras/MAPK, PI3K-AKT, in addition to JAK/STAT ( PIK3R1 and PTK2 ). We confirmed variants with putative driver role of MAP10 , MPZL1 , RPS6KA1 , SETD1B , TAOK2 , TMEM127 , and TNFRSF1A genes, and of genes linked to viral infections ( DDX3X and RSF1 ) and DNA repair ( PAXIP1 ). A truncating mutation of the epigenetic regulator TET2 and a variant likely abrogating PIK3R1- negative regulatory activity were validated. This study significantly furthered the view of the genes and pathways involved in CLPD-NK, indicated similarities with aggressive diseases of NK cells and detected mutated genes targetable by approved drugs, being a step forward to personalized precision medicine for CLPD-NK patients.
Abstract 16566: Effect of Early Metoprolol on Left Ventricular Functional Recovery of Infarcted and Remote Myocardium After ST-Segment Elevation Myocardial Infarction: Feature Tracking Cardiovascular Magnetic Resonance Assessment
Authors: Tomaz Podlesnikar, Gonzalo Pizarro, Rodrigo Fernandez-Jimenez, Javier Sanchez-Gonzalez, Nina Ajmone Marsan, Chiara Bucciarelli-Ducci, Zlatko Fras, Jeroen J Bax, Borja Ibanez, Victoria Delgado
Journal: Circulation (2017)

Introduction: Early metoprolol before reperfusion in ST-segment elevation myocardial infarction (STEMI) has been associated with better outcomes in the METOCARD-CNIC (Effect of Metoprolol in Cardio...
DuoHexaBody-CD37®, a novel biparatopic CD37 antibody with enhanced Fc-mediated hexamerization as a potential therapy for B-cell malignancies
Authors: Simone C. Oostindie, Hilma J. van der Horst, Laurens P. Kil, Kristin Strumane, Marije B. Overdijk, Edward N. van den Brink, Jeroen H. N. van den Brakel, Hendrik J. Rademaker, Berris van Kessel, Juliette van den Noort, Martine E. D. Chamuleau, Tuna Mutis, Margaret A. Lindorfer, Ronald P. Taylor, Janine Schuurman, Paul W. H. I. Parren, Frank J. Beurskens, Esther C. W. Breij
Journal: Blood Cancer Journal (2020)

Abstract Tetraspanin CD37 has recently received renewed interest as a therapeutic target for B-cell malignancies. Although complement-dependent cytotoxicity (CDC) is a powerful Fc-mediated effector function for killing hematological cancer cells, CD37-specific antibodies are generally poor inducers of CDC. To enhance CDC, the E430G mutation was introduced into humanized CD37 monoclonal IgG1 antibodies to drive more efficient IgG hexamer formation through intermolecular Fc-Fc interactions after cell surface antigen binding. DuoHexaBody-CD37, a bispecific CD37 antibody with the E430G hexamerization-enhancing mutation targeting two non-overlapping epitopes on CD37 (biparatopic), demonstrated potent and superior CDC activity compared to other CD37 antibody variants evaluated, in particular ex vivo in patient-derived chronic lymphocytic leukemia cells. The superior CDC potency was attributed to enhanced IgG hexamerization mediated by the E430G mutation in combination with dual epitope targeting. The mechanism of action of DuoHexaBody-CD37 was shown to be multifaceted, as it was additionally capable of inducing efficient antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis in vitro. Finally, potent anti-tumor activity in vivo was observed in cell line- and patient-derived xenograft models from different B-cell malignancy subtypes. These encouraging preclinical results suggest that DuoHexaBody-CD37 (GEN3009) may serve as a potential therapeutic antibody for the treatment of human B-cell malignancies.
Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial
Authors: Chao Zhang, Meini Zhang, Wei Qiu, Hongshan Ma, Xinghu Zhang, Zilong Zhu, Chun-Sheng Yang, Dongmei Jia, Tian-Xiang Zhang, Meng Yuan, Yan Feng, Li Yang, Wenli Lu, Chunshui Yu, Jeffrey L Bennett, Fu-Dong Shi
Journal: The Lancet Neurology (2020)
Effect of Enzalutamide plus Androgen Deprivation Therapy on Health-related Quality of Life in Patients with Metastatic Hormone-sensitive Prostate Cancer: An Analysis of the ARCHES Randomised, Placebo-controlled, Phase 3 Study
Authors: Arnulf Stenzl, Curtis Dunshee, Ugo De Giorgi, Boris Alekseev, Taro Iguchi, Russell Z. Szmulewitz, Thomas W. Flaig, Bertrand Tombal, Robert Morlock, Cristina Ivanescu, Krishnan Ramaswamy, Fred Saad, Andrew J. Armstrong
Journal: European Urology (2020)

In the ARCHES study in metastatic hormone-sensitive prostate cancer (mHSPC), enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival (rPFS) versus ADT alone.To evaluate patient-reported outcomes (PROs) to week 73.ARCHES (NCT02677896) was a randomised, double-blind, placebo-controlled, phase 3 study in mHSPC patients.Enzalutamide (160 mg/day) plus ADT or placebo plus ADT.PROs were assessed at baseline, week 13, and every 12 wk until disease progression using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Prostate 25 (QLQ-PR25), Functional Assessment of Cancer Therapy-Prostate (FACT-P), Brief Pain Inventory Short Form, and EuroQoL 5-Dimensions, 5-Levels (EQ-5D-5 L) instruments. Endpoints included time to first (TTFD) and first confirmed (TTFCD) clinically meaningful deterioration (using predefined questionnaire thresholds) in health-related quality of life (HRQoL) and pain.A total of 1150 patients received ADT plus enzalutamide (n = 574) or placebo (n = 576). Baseline PRO scores indicated high HRQoL and low pain, which was generally maintained in both groups. There were no statistically significant (nominal p > 0.05) between-group differences that occurred in both TTFD and TTFCD together for QLQ-PR25 and FACT-P scores. Enzalutamide significantly delayed TTFD in worst pain (by ∼3 mo; nominal p = 0.032), pain severity (nominal p = 0.021), and EQ-5D-5 L visual analogue scale score (nominal p = 0.0070) versus placebo (not significant for confirmed deterioration for pain outcomes). Enzalutamide delays deterioration in several HRQoL subscales and pain severity in high-volume disease.Enzalutamide plus ADT enables men with mHSPC to maintain high-functioning HRQoL and low symptom burden.This study examined the effect on health-related quality of life and pain of adding enzalutamide or placebo to androgen deprivation therapy for patients with metastatic hormone-sensitive prostate cancer. Addition of enzalutamide allowed patients to maintain their health-related quality of life.
The Immunosuppressive Niche of Soft-Tissue Sarcomas is Sustained by Tumor-Associated Macrophages and Characterized by Intratumoral Tertiary Lymphoid Structures
Authors: Lingling Chen, Teniola Oke, Nicholas Siegel, Gady Cojocaru, Ada J. Tam, Richard L. Blosser, Jessica Swailes, John A. Ligon, Andriana Lebid, Carol Morris, Adam Levin, Daniel S. Rhee, Fabian M. Johnston, Jonathan B. Greer, Christian F. Meyer, Brian H. Ladle, Elizabeth D. Thompson, Elizabeth A. Montgomery, Woonyoung Choi, David J. McConkey, Robert A. Anders, Drew M. Pardoll, Nicolas J. Llosa
Journal: Clinical Cancer Research (2020)

Clinical trials with immune checkpoint inhibition in sarcomas have demonstrated minimal response. Here, we interrogated the tumor microenvironment (TME) of two contrasting soft-tissue sarcomas (STS), rhabdomyosarcomas and undifferentiated pleomorphic sarcomas (UPS), with differing genetic underpinnings and responses to immune checkpoint inhibition to understand the mechanisms that lead to response.Utilizing fresh and formalin-fixed, paraffin-embedded tissue from patients diagnosed with UPS and rhabdomyosarcomas, we dissected the TME by using IHC, flow cytometry, and comparative transcriptomic studies.Our results demonstrated both STS subtypes to be dominated by tumor-associated macrophages and infiltrated with immune cells that localized near the tumor vasculature. Both subtypes had similar T-cell densities, however, their in situ distribution diverged. UPS specimens demonstrated diffuse intratumoral infiltration of T cells, while rhabdomyosarcomas samples revealed intratumoral T cells that clustered with B cells near perivascular beds, forming tertiary lymphoid structures (TLS). T cells in UPS specimens were comprised of abundant CD8+ T cells exhibiting high PD-1 expression, which might represent the tumor reactive repertoire. In rhabdomyosarcomas, T cells were limited to TLS, but expressed immune checkpoints and immunomodulatory molecules which, if appropriately targeted, could help unleash T cells into the rest of the tumor tissue.Our work in STS revealed an immunosuppressive TME dominated by myeloid cells, which may be overcome with activation of T cells that traffic into the tumor. In rhabdomyosarcomas, targeting T cells found within TLS may be key to achieve antitumor response.
Venous Thromboembolism in Emergency General Surgery Patients—A Call to Action to Improve Data, Clinical Care, and Patient Outcomes
Authors: Patrick B. Murphy, Elliott R. Haut
Journal: JAMA Surgery (2020)

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Factors Contributing to Major Neurological Complications From Vein of Galen Malformation Embolization
Authors: Kartik Bhatia, Vitor Mendes Pereira, Timo Krings, Karel ter Brugge, Hans Kortman, Peter Dirks, Derek Armstrong, Manohar Shroff, Prakash Muthusami
Journal: JAMA Neurology (2020)

<h3>Importance</h3> Major neurological complications from the embolization of vein of Galen malformations (VOGMs) are poorly understood. We provide a detailed analysis of contributors to periprocedural neurological complications and lessons learned. <h3>Objective</h3> To assess the rate of major periprocedural neurological complications following VOGM embolization with major procedural and strategic contributors. <h3>Design, Setting, and Participants</h3> This retrospective cohort study was conducted at a quarternary referral pediatric hospital (Hospital for Sick Children; Toronto, Ontario, Canada) from January 1999 to December 2018 with a mean clinical follow-up of 44.7 months; all children with VOGM diagnosed and/or treated were eligible (n = 48). Thirty-three patients who underwent endovascular treatment were included. <h3>Interventions</h3> Endovascular staged transarterial embolization performed in 33 patients over 91 sessions. <h3>Main Outcomes and Measures</h3> The primary outcome was the rate of periprocedural neurological complications (occurring within 1 week of embolization). The secondary outcomes were mortality, long-term neurological outcomes, and contributing anatomical and management factors to neurological complications. <h3>Results</h3> Of 33 patients who underwent embolization (31 boys [64.6%]; 17 girls [35.4%]; median age at first embolization, 4 months [range, 0-29 months]), 10 patients (30.3%) developed major periprocedural neurological complications. Five of these patients died. Univariate logistic regression analyses identified internal cerebral vein drainage to the main venous sac of the VOGM and use of a microcatheter with a distal outer diameter of more than 2.0F as significant predictors of poor neurological outcomes. Lessons learned from our experience include the need to assess the internal cerebral vein drainage pattern on preprocedural magnetic resonance venography, avoidance of excessive embolization into the venous sac, treatment of more distal fistulae before proximal fistulae to avoid a sump effect, and preferably use of smaller (&lt;2.0F outer diameter) microcatheters in neonatal embolization procedures. <h3>Conclusions and Relevance</h3> In this cohort, 10 patients with VOGM treated with embolization (30.3%) experienced major periprocedural neurological complications, half of whom died. While these outcomes are superior to historic conservative and surgical treatment results, ongoing improvements in treatment and pretreatment diagnostic approaches are needed. Awareness of the lessons learned from our experience can help to avoid similar complications in the future for this vulnerable population.
Immunogenomic identification and characterization of granulocytic myeloid-derived suppressor cells in multiple myeloma
Authors: Cristina Perez, Cirino Botta, Aintzane Zabaleta, Noemi Puig, Maria-Teresa Cedena, Ibai Goicoechea, Daniel Alameda, Edurne San José-Eneriz, Juana Merino, Paula Rodríguez-Otero, Catarina Maia, Diego Alignani, Patricia Maiso, Irene Manrique, David Lara-Astiaso, Amaia Vilas-Zornoza, Sarai Sarvide, Caterina Riillo, Marco Rossi, Laura Rosiñol, Albert Oriol, María-Jesús Blanchard, Rafael Rios, Anna Sureda, Jesus Martin, Rafael Martinez, Joan Bargay, Javier de la Rubia, Miguel-Teodoro Hernandez, Joaquin Martinez-Lopez, Alberto Orfao, Xabier Agirre, Felipe Prosper, Maria-Victoria Mateos, Juan-José Lahuerta, Joan Blade, Jesús F. San-Miguel, Bruno Paiva
Journal: Blood (2020)