tbuckley/cabot-search huggingface dataset:
Nivolumab in metastatic nonclear cell renal cell carcinoma: First results of the AcSe prospective study.
Authors: Laurence Albiges, Damien Pouessel, Marie Beylot-Barry, Guido Bens, Diane Pannier, Céline Gavoille, Stephane Oudard, Sylvie Chevret, Natalie Hoog Labouret, Frédéric Legrand, Clotilde Simon, Assia Lamrani-Ghaouti, Bernard Escudier, Aurelien Marabelle, Aude Flechon
Journal: Journal of Clinical Oncology (2020)

699 Background: AcSe Nivolumab (N), is a non-randomised, open-label, multicentric study to investigate the efficacy and safety of nivolumab monotherapy in patients (pts) with specific rare cancers (NCT03012581). We report on the non-clear cell renal cell carcinoma (RCC) cohort. Methods: Primary endpoint was objective response rate (ORR) at 12 weeks according to RECIST1.1. All pts receives N at 240mg IV every 2 weeks. Secondary endpoints included progression free survival (PFS), overall survival (OS), best response, and safety. Results: Between 07/2017 and 02/2019, 50 pts have been enrolled across 13 institutions. Median age was 61.4 years old, 70% were male. ECOG PS was 0, 1, 2, in 29%, 63% and 8% of pts respectively. Histological types were papillary (pRCC) type 2 (41%), chromophobe (18%), pRCC type I (10%), pRCC unclassified (8%), collecting duct carcinoma (CDC) (8%), and others (including predominant sarcomatoid, renal medullary carcinoma, MITF associated RCC, unclassified RCC). N was used in first line in 16%, second line in 54% and third line or beyond in 30%. IMDC risk group was 14%, 70% and 16% for good, intermediate and poor risk respectively. With a median follow up of 10.4 months (mo), 42 pts had discontinued N. The 12 weeks-ORR was 6% (3 PR), with stable disease in 49% and PD in 44% of pts. The best ORR was 10%. Median PFS was 3.9 mo (IC95% [2.9; 8.3]). At time of analysis, 25 pts (50%) had died and 12-months OS rate was 47.7% (IC95% [33.5; 67.8]). Overall, 31 pts (62%) have presented at least one grade ≥ 3 AE. No new safety signal with N was reported. 12 weeks-ORR and best ORR according to distinct histology are presented in table 1. Pts with PR were 1pRCC type 2, 1pRCC type 1, 1 CDC, 1 MITF RCC and 1 unclassified. Conclusions: We report the first prospective study of N single agent in non-clear cell RCC. N demonstrates limited activity in a pretreated and heterogeneous non- clear cell RCC population. Interestingly 1/4 CDC developed PR while no response was noted in chromophobe RCC. Clinical trial information: NCT03012581. [Table: see text]
Burden of osteoarthritis in China, 1990–2017: findings from the Global Burden of Disease Study 2017
Authors: Huibin Long, Xinying Zeng, Qiang Liu, Haidong Wang, Theo Vos, Yunfei Hou, Chutong Lin, Yudian Qiu, Kai Wang, Dan Xing, Yuqing Zhang, Maigeng Zhou, Jianhao Lin
Journal: The Lancet Rheumatology (2020)
EoE Biopsies have Elevated and Activated Mast Cells that Produce Cytokines and Chemokines that Drive Disease Pathogenesis
Authors: Melina Butuci, Emily Brock, Julia Schanin, Henrik Rasmussen, Bhupinder Singh, Richard Drake, Kathryn Peterson, Brad Youngblood
Journal: Journal of Allergy and Clinical Immunology (2020)
A multicenter retrospective study of 223 patients with t(14;16) in multiple myeloma
Authors: Sarah Goldman‐Mazur, Artur Jurczyszyn, Jorge J. Castillo, Anna Waszczuk‐Gajda, Norbert Grząśko, Jakub Radocha, Max Bittrich, K. Martin Kortüm, Alessandro Gozzetti, Lidia Usnarska‐Zubkiewicz, Julio Davila Valls, David S. Jayabalan, Ruben Niesvizky, Julia Kelman, Daniel Coriu, Laura Rosiñol, Łukasz Szukalski, Veronica González‐Calle, Maria V. Mateos, Krzysztof Jamroziak, Iwona Hus, Irit Avivi, Yael Cohen, Anna Suska, Aimee Chappell, Deepu Madduri, Saurabh Chhabra, Ariel Kleman, Parameswaran Hari, Michel Delforge, Paweł Robak, Massimo Gentile, Izabela Kozłowska, Stuart L. Goldberg, Jacek Czepiel, Rebecca Silbermann, Adam J. Olszewski, Peter Barth, Gabor Mikala, Chor S. Chim, Monika Długosz‐Danecka, Sebastian Grosicki, David H. Vesole
Journal: American Journal of Hematology (2020)

The t(14;16) translocation, found in 3%-5% of newly diagnosed (ND) multiple myeloma (MM), has been associated with adverse outcomes. However, the studies establishing the characteristics of t(14;16) included solely small cohorts. The goal of the current international, multicenter (n = 25 centers), retrospective study was to describe the characteristics and outcomes of t(14;16) patients in a large, real-world cohort (n = 223). A substantial fraction of patients had renal impairment (24%) and hemoglobin <10 g/dL (56%) on initial presentation. Combined therapy of both immunomodulatory drug and proteasome inhibitor (PI) in the first line was used in 35% of patients. Autologous stem cell transplantation was performed in 42% of patients. With a median follow up of 4.1 years (95% CI 3.7-18.7), the median progression-free survival (PFS) and overall survival (OS) from first line therapy were 2.1 years (95% CI 1.5-2.4) and 4.1 years (95% CI 3.3-5.5), respectively. Worse OS was predicted by age > 60 years (HR = 1.65, 95% CI [1.05-2.58]), as well as revised International Scoring System (R-ISS) 3 (vs R-ISS 2; HR = 2.59, 95% CI [1.59-4.24]). In conclusion, based on the largest reported cohort of t(14;16) patients, quarter of this subset of MM patients initially presents with renal failure, while older age and the R-ISS 3 predict poor survival.
Abstract 13228: The Effect of Gestational Age and Size at Birth on Brain Injury and Developmental Outcomes in Congenital Heart Disease
Authors: Shalin Parekh, Martina A Steurer, Vann Chau, Whitnee Hogan, Duan Xu, Steven Miller, Patrick S McQuillen, Shabnam Peyvandi
Journal: Circulation (2019)

Background: Early delivery and size at birth are known to be independent risk factors for neurodevelopmental (ND) impairments among patients with complex congenital heart disease (CHD). The aim of ...
Hereditary angioedema (HAE) prophylaxis with plasma kallikrein inhibitors: Role of target binding kinetics, pharmacokinetics and treatment adherence
Authors: Rangaraj Narayanan, Haobin Luo, Zhiwei Zhang, Paul Jasper, Peng Lu, Salome Juethner, Dan Sexton
Journal: Journal of Allergy and Clinical Immunology (2020)
Genome-wide MNase hypersensitivity assay unveils distinct classes of open chromatin associated with H3K27me3 and DNA methylation in Arabidopsis thaliana
Authors: Hainan Zhao, Wenli Zhang, Tao Zhang, Yuan Lin, Yaodong Hu, Chao Fang, Jiming Jiang
Journal: Genome biology (2020)

Abstract Background Regulation of transcription depends on interactions between cis -regulatory elements (CREs) and regulatory proteins. Active CREs are imbedded in open chromatin that are accessible to nucleases. Several techniques, including DNase-seq, which is based on nuclease DNase I, and ATAC-seq, which is based on transposase Tn5, have been widely used to identify genomic regions associated with open chromatin. These techniques have played a key role in dissecting the regulatory networks in gene expression in both animal and plant species. Results We develop a technique, named MNase hypersensitivity sequencing (MH-seq), to identify genomic regions associated with open chromatin in Arabidopsis thaliana . Genomic regions enriched with MH-seq reads are referred as MNase hypersensitive sites (MHSs). MHSs overlap with the majority (~ 90%) of the open chromatin identified previously by DNase-seq and ATAC-seq. Surprisingly, 22% MHSs are not covered by DNase-seq or ATAC-seq reads, which are referred to “specific MHSs” (sMHSs). sMHSs tend to be located away from promoters, and a substantial portion of sMHSs are derived from transposable elements. Most interestingly, genomic regions containing sMHSs are enriched with epigenetic marks, including H3K27me3 and DNA methylation. In addition, sMHSs show a number of distinct characteristics including association with transcriptional repressors. Thus, sMHSs span distinct classes of open chromatin that may not be accessible to DNase I or Tn5. We hypothesize that the small size of the MNase enzyme relative to DNase I or Tn5 allows its access to relatively more condensed chromatin domains. Conclusion MNase can be used to identify open chromatin regions that are not accessible to DNase I or Tn5. Thus, MH-seq provides an important tool to identify and catalog all classes of open chromatin in plants.
Suckling, Feeding, and Swallowing: Behaviors, Circuits, and Targets for Neurodevelopmental Pathology
Authors: Thomas M. Maynard, Irene E. Zohn, Sally A. Moody, Anthony-S. LaMantia
Journal: Annual Review of Neuroscience (2020)

All mammals must suckle and swallow at birth, and subsequently chew and swallow solid foods, for optimal growth and health. These initially innate behaviors depend critically upon coordinated development of the mouth, tongue, pharynx, and larynx as well as the cranial nerves that control these structures. Disrupted suckling, feeding, and swallowing from birth onward—perinatal dysphagia—is often associated with several neurodevelopmental disorders that subsequently alter complex behaviors. Apparently, a broad range of neurodevelopmental pathologic mechanisms also target oropharyngeal and cranial nerve differentiation. These aberrant mechanisms, including altered patterning, progenitor specification, and neurite growth, prefigure dysphagia and may then compromise circuits for additional behavioral capacities. Thus, perinatal dysphagia may be an early indicator of disrupted genetic and developmental programs that compromise neural circuits and yield a broad range of behavioral deficits in neurodevelopmental disorders.
Xenosiderophore Utilization Promotes Bacteroides thetaiotaomicron Resilience during Colitis
Authors: Wenhan Zhu, Maria G. Winter, Luisella Spiga, Elizabeth R. Hughes, Rachael Chanin, Aditi Mulgaonkar, Jenelle Pennington, Michelle Maas, Cassie L. Behrendt, Jiwoong Kim, Xiankai Sun, Daniel P. Beiting, Lora V. Hooper, Sebastian E. Winter
Journal: Cell Host & Microbe (2020)
Assessing focality of dominant tumor on serial biopsy in an active surveillance cohort: Implications for focal therapy.
Authors: Vittorio Fasulo, Janet E. Cowan, Samuel L. Washington, Hao Gia Nguyen, Katsuto Shinohara, Paolo Casale, Peter Carroll
Journal: Journal of Clinical Oncology (2020)

352 Background: Focal therapy (FT) has been proposed as an alternative to active surveillance (AS) for men with low/intermediate risk prostate cancer (PCa). We aim to understand progression within and outside the dominant tumor (DT) in terms of changes in focality, tumor volume and histologic grading on serial biopsy of the prostate (Bx) to identify reasonable candidates for FT. Methods: Men enrolled on AS at UCSF between 1996 and 2017 with low\intermediate risk PCa at diagnosis (PSA &lt; 20ng\ml, stage cT1\2, Gleason score (GS) ≤3+4) and at least 1 Bx after diagnosis were included. All Bx were systematic. Changes in Bx laterality and/or grade were assessed over time. DT was defined as the tumor with highest GS and size on Bx confined to 1 or 2 contiguous sextants. Those with unifocal disease (Un), multifocal in contiguous sextants (Mc), or a small volume of GS 3+3 on the contralateral side were considered candidates for FT. Results: Among 1272 men, mean age was 62 years, median PSA was 5.42 ng\ml and median follow up was 78 months (IQR 46-108). Median number of Bx was 3 (min 2, max 12) and 18% had &gt;5 Bx. At diagnosis 90% and 10% of patients had GS 3+3 and 3+4 disease respectively. At first surveillance Bx (fsBX) findings were negative in 20%, unchanged in 56% and upgraded in 24%. Findings were similar at the following 3 Bx. Across all biopsies 27% were negative and 7-year upgrade-free survival was 39%. At diagnosis, 88% of tumors were in locations viable for FT (50% Un and 38% Mc versus 12% multifocal in non-contiguous sextants (Mn-c)). At fsBX, 21% of Bx were negative and 85% of the remainder were viable for FT (29% Un and 56% Mc versus 15% Mn-c). Across all Bx DT remained stable in 592 (47%), changed prostate side or expanded to bilateral in 128 (10%), upgraded on the original dominant side in 407 (32%), and upgraded on the opposite side in 145 (11%). Of those upgraded on the non-dominant side, 74% were GS 3+4, 21% were GS 4+3 and 5% were GS ≥4+4. Conclusions: On serial biopsy, tumor location remains relatively stable and significant changes in grade and/or volume occur in the DT. A low percentage of patients show significant progression outside the DT. Such information is relevant when considering FT in this patient population.
Abstract 14640: Serum Immunoglobulin G4 Levels Are Associated With High-Risk Coronary Plaque Independent of Established Cardiovascular Risk Factors
Authors: Aiko Sakamoto, Nobukazu Ishizaka, Masae Uehara, Jiro Ando, Issei Komuro
Journal: Circulation (2017)

Background: Atherosclerotic coronary plaques with a large lipid core have a strong association with acute coronary syndrome. Although inflammatory processes contribute to the development of vulnera...
Pathogenic Variants in CEP85L Cause Sporadic and Familial Posterior Predominant Lissencephaly
Authors: Meng-Han Tsai, Alison M. Muir, Won-Jing Wang, Yi-Ning Kang, Kun-Chuan Yang, Nian-Hsin Chao, Mei-Feng Wu, Ying-Chao Chang, Brenda E. Porter, Laura A. Jansen, Guillaume Sebire, Nicolas Deconinck, Wen-Lang Fan, Shih-Chi Su, Wen-Hung Chung, Edith P. Almanza Fuerte, Michele G. Mehaffey, Ching-Ching Ng, Chung-Kin Chan, Kheng-Seang Lim, Richard J. Leventer, Paul J. Lockhart, Kate Riney, John A. Damiano, Michael S. Hildebrand, Ghayda M. Mirzaa, William B. Dobyns, Samuel F. Berkovic, Ingrid E. Scheffer, Jin-Wu Tsai, Heather C. Mefford
Journal: Neuron (2020)
Spatio-Temporal Analysis of the Impact of Airborne Pollen, Ambient Air Pollution, and Land Cover on the Sales of Medications Used to Treat Asthma and Allergies, in 8 Cities, in Metropolitan France
Authors: Karen Hernandez, Julie Prud'homme, Stéphane Sclison, Isabella Annesi-Maesano
Journal: Journal of Allergy and Clinical Immunology (2020)
Association of Leukocyte Telomere Length With Mortality Among Adult Participants in 3 Longitudinal Studies
Authors: Konstantin G. Arbeev, Simon Verhulst, Troels Steenstrup, Jeremy D. Kark, Olivia Bagley, Charles Kooperberg, Alexander P. Reiner, Shih-Jen Hwang, Daniel Levy, Annette L. Fitzpatrick, Kaare Christensen, Anatoliy I. Yashin, Abraham Aviv
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Leukocyte telomere length (LTL) is a trait associated with risk of cardiovascular disease and cancer, the 2 major disease categories that largely define longevity in the United States. However, it remains unclear whether LTL is associated with the human life span. <h3>Objective</h3> To examine whether LTL is associated with the life span of contemporary humans. <h3>Design, Setting, and Participants</h3> This cohort study included 3259 adults of European ancestry from the Cardiovascular Health Study (CHS), Framingham Heart Study (FHS), and Women’s Health Initiative (WHI). Leukocyte telomere length was measured in 1992 and 1997 in the CHS, from 1995 to 1998 in the FHS, and from 1993 to 1998 in the WHI. Data analysis was conducted from February 2017 to December 2019. <h3>Main Outcomes and Measures</h3> Death and LTL, measured by Southern blots of the terminal restriction fragments, were the main outcomes. Cause of death was adjudicated by end point committees. <h3>Results</h3> The analyzed sample included 3259 participants (2342 [71.9%] women), with a median (range) age of 69.0 (50.0-98.0) years at blood collection. The median (range) follow-up until death was 10.9 (0.2-23.0) years in CHS, 19.7 (3.4-23.0) years in FHS, and 16.6 (0.5-20.0) years in WHI. During follow-up, there were 1525 deaths (482 [31.6%] of cardiovascular disease; 373 [24.5%] of cancer, and 670 [43.9%] of other or unknown causes). Short LTL, expressed in residual LTL, was associated with increased mortality risk. Overall, the hazard ratio for all-cause mortality for a 1-kilobase decrease in LTL was 1.34 (95% CI, 1.21-1.47). This association was stronger for noncancer causes of death (cardiovascular death: hazard ratio, 1.28; 95% CI, 1.08-1.52; cancer: hazard ratio, 1.13; 95% CI, 0.93-1.36; and other causes: hazard ratio, 1.53; 95% CI, 1.32-1.77). <h3>Conclusions and Relevance</h3> The results of this study indicate that LTL is associated with a natural life span limit in contemporary humans.
Case Report 18F-FDG PET/CT of Pseudomyogenic Hemangioendothelioma
Authors: Nicolas Plouznikoff, Stephanie A. Mourad, Sophie Turpin, Robert E. Turcotte, David A. Mitchell, Raymond Lambert
Journal: Clinical Nuclear Medicine (2020)

Hemangioendotheliomas are a heterogeneous group of vascular neoplasm that may affect the liver, bone, and soft tissues. Among its variants, pseudomyogenic hemangioendothelioma is rarely encountered. Pseudomyogenic hemangioendothelioma is usually characterized by multiple soft tissue lesions, with occasional bone lesions. Fewer than 20 cases with exclusive involvement of bone structures have been reported. We describe a case of pseudomyogenic hemangioendothelioma involving multiple bony structures but without soft tissue involvement in a 7-year-old girl, imaged with F-FDG PET/CT at diagnosis and during treatment with mammalian target of rapamycin inhibitors.
Efficacy of Dupilumab in Adolescents With Moderate-to-Severe Atopic Dermatitis With and Without Comorbid Asthma: Subgroup Analysis From a Phase 3 Trial
Authors: Mark Boguniewicz, Weily Soong, Paola Mina-Osorio, Randy Prescilla, Zhen Chen, Ashish Bansal
Journal: Journal of Allergy and Clinical Immunology (2020)
Effect of process parameters on additive-free electrospinning of regenerated silk fibroin nonwovens
Authors: Alexander Kopp, Ralf Smeets, Martin Gosau, Nadja Kröger, Sandra Fuest, Marius Köpf, Magnus Kruse, Judith Krieger, Rico Rutkowski, Anders Henningsen, Simon Burg
Journal: Bioactive Materials (2020)

Silk fibroin is a biomaterial with multiple beneficial properties for use in regenerative medicine and tissue engineering. When dissolving and processing the reconstituted silk fibroin solution by electrospinning, the arrangement and size of fibers can be manifold varied and according fiber diameters reduced to the nanometer range. Such nonwovens show high porosity as well as potential biocompatibility. Usually, electrospinning of most biomaterials demands for the application of additives, which enable stable electrospinning by adjusting viscosity, and are intended to evaporate during processing or to be washed out afterwards. However, the use of such additives increases costs and has to be taken into account in terms of biological risks when used for biomedical applications. In this study, we explored the possibilities of additive-free electrospinning of pure fibroin nonwovens and tried to optimize process parameters to enable stable processing. We used natural silk derived from the mulberry silkworm Bombyx mori. After degumming, the silk fibroin was dissolved and the viscosity of the spinning solution was controlled by partial evaporation of the initial solving agent. This way, we were able to completely avoid the use of additives and manufacture nonwovens, which potentially offer higher biocompatibility and reduced immunogenicity. Temperature and relative humidity during electrospinning were systematically varied (25-35 °C, 25-30% RH). In a second step, the nonwovens optionally underwent methanol treatment to initiate beta-sheet formation in order to increase structural integrity and strength. Comprehensive surface analysis on the different nonwovens was performed using scanning electron microscopy and supplemented by additional mechanical testing. Cytotoxicity was evaluated using BrdU-assay, XTT-assay, LDH-assay and live-dead staining. Our findings were, that an increase of temperature and relative humidity led to unequal fiber diameters and defective nonwovens. Resistance to penetration decreased accordingly. The most uniform fiber diameters of 998 ± 63 nm were obtained at 30 °C and 25% relative humidity, also showing the highest value for resistance to penetration (0.20 N). The according pure fibroin nonwoven also showed no signs of cytotoxicity. However, while the biological response showed statistical evidence, the material characteristics showed no statistically significant correlation to changes of the ambient conditions within the investigated ranges. We suggest that further experiments should explore additional ranges for temperature and humidity and further focus on the repeatability of material properties in dependency of suitable process windows.
Stereotactic radiotherapy +/- HDR boost for unfavorable-risk prostate cancer: Comparison of efficacy, survival, and late toxicity outcomes.
Authors: Andrew Loblaw, Patrick Cheung, Danny Vesprini, Stanley K. Liu, William Chu, Hans T. Chung, Gerard Morton, Bindu Musunuru, Andrea Deabreu, Melanie Davidson, Ananth Ravi, Joelle Helou, Ling Ho, Liying Zhang
Journal: Journal of Clinical Oncology (2020)

372 Background: The ASCO/CCO guidelines recommend brachytherapy boost for all eligible intermediate- or high-risk localized prostate cancer patients. Stereotactic body radiotherapy (SBRT) is an emerging treatment for prostate cancer but its use in high risk disease is limited. We compare efficacy, survival and late toxicity outcomes in patients treated on 2 prospective, phase 2 protocols that both use pelvic SBRT and androgen deprivation therapy (ADT). One used MR-guided HDR brachytherapy boost (SPARE) and the other uses a SBRT boost (SATURN). Methods: SPARE was a phase I/II study where intermediate (IR) or high-risk (HR) prostate cancer patients received HDR-BT 15Gy x 1 to the prostate and up to 22.5Gy to the MRI nodule and followed by gantry-based SBRT 25Gy in 5 weekly fractions delivered to pelvis. ADT was used for 6-18 months. SATURN was a phase II study where high risk patients received 40Gy to prostate and 25Gy to pelvis along in 5 weekly fractions with 12-18 months ADT. CTCAEv3 was used to assess toxicities and was captured q6months x 5 years. Biochemical failure (BF; nadir + 2 definition), nadir PSA, proportion of patients with PSA &lt; 0.4 ng/ml at 4 years (4yPSARR), incidence of salvage therapy, cause specific survival were calculated. Day 0 was first day of RT for all time-to-event analyses. Results: Thirty-two patients (NCCN 3% favorable IR, 47% unfavorable IR (UIR), 50% HR) completed SPARE while 30 patients (7% UIR, 93% HR) completed SATURN. Median follow-up of 50 and 48 months, respectively. Actuarial 4-year BF was 11.5% and 0%. Median nPSA was 0.02 ng/ml for both studies. 4yPSARR was 69% and 93%. 4-year cause-specific survival was 96% and 100%. Toxicities are listed in Table. Conclusions: In the context of SBRT pelvis and ADT, SBRT boost provides similar efficacy for unfavorable risk prostate cancer with acceptable but worse toxicities compared to HDR boost. A randomized study is recommended to answer this question. Clinical trial information: 01953055. [Table: see text]
Is He OK?
Authors: Erica Andrist
Journal: New England Journal of Medicine (2020)

In the middle of the night, the teenage boy is awake, coughing, desaturated, hypotensive. His monitors are squalling. Soon, it is better: some fentanyl, rocuronium, a little fluid. The room quiets. "Is he OK?" his mother asks. "Yes," I say, squeezing her shoulder.