tbuckley/cabot-search huggingface dataset:
Covid-19: Drug firms warn stockpiles have been eroded amid fears of no deal Brexit
Authors: Gareth Iacobucci
Journal: BMJ (2020)

Covid-19: Drug firms warn stockpiles have been eroded amid fears of no deal Brexit Gareth IacobucciThe BMJ Drug industry leaders have warned UK government that stockpiles of some drugs have been eroded by covid-19, leaving supplies even more vulnerable if a no deal Brexit occurs.
Screening for Unhealthy Drug Use
Authors: Richard Saitz
Journal: JAMA (2020)

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FRI0620-HPR THE EFFECT OF THERMOFORMABLE FOOT ORTHOSES ON WALKING IN RHEUMATOID ARTHRITIS PATIENTS: PRELIMINARY RESULTS FROM AN OPEN CLINICAL TRIAL
Authors: S. Fellous, H. Rkain, A. Ilham, L. Benzakour, T. Latifa, N. Alami, R. Guieu, Y. Jammes, N. Hajjaj-Hassouni, F. Allali
Journal: Annals of the Rheumatic Diseases (2020)

Background: Foot pain is common in rheumatoid arthritis and appears to persist despite modern day medical management. Objectives: To evaluate the impact of thermoformable foot orthoses on walking in rheumatoid arthritis (RA) patients. Methods: This is a open clinical trial, that included 14 consecutive patients (85,7% female, mean age 54,8 ± 10 years) with RA (median duration of progression of 9 [5-12] years), the average DAS28 was 2,7+/-1,2 and the functional impact objectified by the Health Assessment Questionnaire (HAQ) was on average 0.9 ± 0.7. The foot problem was bilateral in 100% and inaugural in 85.7% of the cases. The 14 rheumatoid subjects were examined and appropriate foot orthoses were prescribed according to each patient’s needs. All the patients were evaluated at baseline and 8 weeks after use of orthoses. Gait pain, difficulty walking and the 10 Meter Walk test were noted at each appointment. We used dynamic baropodometric analysis to assess postural evaluation. We calculated the lateral-medial index of each foot before and after the use of orthoses. Table 1. Assessment of walking before and after the use of orthoses Before orthoses After orthoses p Pain when walking*(EVA 0-10) 5 [3-5,2] 0 [0-2] 0,002 Difficulty walking* (0-10) - In house 4 [3-5,2] 2 [0-2] 0,002 - Outside 6 [4,7-7] 2 [1,5-2,5] 0,02 10 Meter Walk test**(Normal comfortable speed) - Nomber of steps 18,64 ± 3,7 16,9 ± 5 0,2 - Duration (sec) 11,9 ± 4,6 11,8 ± 5,2 0,9 - Walking speed (m/min) 56,4 ±17,7 58,6 ± 20,3 0,6 latero-medial (L/M) index** - L/M index of the right foot 1,18 ± 0,17 1,23 ± 0,23 0,1 - L/M index of the left foot 1,25 ± 0,17 1,26 ± 0,19 0,9 *median and quartile **average and standard deviation p significant if&lt; 0,05 Results: A significant decrease in walking pain (p = 0.002) and difficulty walking (p = 0.02) was found with the use of orthoses. The variations in 10 meter walk test and dynamic baropodometric parameters were not significant (p&gt;0,05). There were no significant correlations between pain and difficulty walking, the progression of RA, the duration of foot damage and the functional impact measured by the HAQ. Conclusion: Thermoformable foot orthoses significantly reduced pain and difficulty walking. The absence of factors associated with pain and difficulty walking could possibly be related to the small sample size. Disclosure of Interests: None declared
Mesenchymal stromal cells as a salvage treatment for confirmed acute respiratory distress syndrome: preliminary data from a single-arm study
Authors: Haijin Lv, Wenjie Chen, Andy Peng Xiang, Qi Zhang, Yang Yang, Huimin Yi, Haijin Lv, Huimin Yi, Xiaomeng Yi, Yuling An, Xuxia Wei, Pinglan Lu, Mingming Fan, Xunan Gong, Jianrong Liu, Jun Guo, Mi Zhou, Jianrong Liu, Yang Yang, Fei Han, Guihua Chen, Yanhong Wang, Yunfeng Shi, Benquan Wu, Ying Xian, Xiaogang Bi, Kouxing Zhang, Qi Zhang, Wenjie Chen, Jianxi Lu, Chang Liu, Yuefei Guo
Journal: Intensive Care Medicine (2020)
Abstract IA06: The tissue-specific microenvironment in primary tumors and metastases
Authors: Zena Werb, Hugo Gonzalez, Juliane Winkler, Eric Berens
Journal: Cancer Research (2020)

Abstract Cancer cells within tumors exist in specialized niches in the microenvironment. The tumor cells are heterogeneous and can have properties as divergent as self-renewal, tumor initiation and repopulation potential, dormancy, evasion of cell death, and metastasis. Metastasis is the major cause of poor outcome in breast cancer. The microenvironment is critical for regulating multiple aspects of tumor progression and metastasis. Understanding the processes involved in metastasis is critical for developing new preventative and therapeutic strategies. We have analyzed the matrix environment and its function in tumor progression using in vivo imaging, genetic models of breast cancer, patient-derived xenografts, organotypic cultures, and patient samples. We have found that the matrix environment and the innate immune cells responding to the primary tumor and infiltrating the metastatic sites are critical for regulating tumor invasion and metastasis. Indeed, the inflammatory microenvironment of metastatic sites was distinct from that of the parental tumor and the normal tissue, even before metastasis takes hold. Interplay between nonmetastatic primary breast cancer and innate immune response acts to control metastatic progression. At the single-cell level, early-stage metastatic cells possess a distinct stemlike gene expression signature. The metastatic cells and the microenvironment are distinct in different metastatic sites and from the primary tumor. Micrometastatic cells are distinct due to their increased expression of basal, stem cell, prosurvival, and dormancy-associated genes. In contrast, cells from macrometastases are similar to primary tumor cells, which are more differentiated and heterogeneous. We validated our findings with a large primary breast cancer tissue microarray and pleural effusions from breast cancer patients. These results suggest that novel cancer immunotherapies that activate and augment the function of antitumoral myeloid subpopulations could have therapeutic potential and be clinically important for patients with advanced breast cancer. Citation Format: Zena Werb, Hugo Gonzalez, Juliane Winkler, Eric Berens. The tissue-specific microenvironment in primary tumors and metastases [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr IA06.
William Ross Cattell
Authors: Laurence Baker, Judith Webb
Journal: BMJ (2020)

William Ross Cattell (“Bill”) was a pioneer in nephrology at St Bartholomew’s Hospital. He was an excellent clinician, much respected by his colleagues, and he undertook important research on urinary tract infection, renal imaging, and a wide variety of other nephrological topics.

Bill grew up on a farm in north east Scotland. There he enjoyed the freedom of the countryside but also absorbed a strong work ethic from his parents as he and his two older brothers helped on the farm. He was educated at Inverness Royal Academy, where he was a gold medallist in physics and chemistry and an Anderson prize winner in natural sciences. He studied medicine at Edinburgh, and graduated with first class merits in five subjects.

After a house physician post at Raigmore Hospital in Inverness, national service took him to the Suez Canal Zone, first as a regimental medical officer, and then in the busy military hospital, where he was responsible for two tuberculosis wards. By the time Bill left the army, he had decided on a career in hospital medicine. He returned to Edinburgh Royal Infirmary as house physician to Professor Stanley Davidson. Two further posts in Edinburgh in chest medicine led to a post at the Brompton Hospital in London. While there, he passed the Edinburgh and London MRCP examinations.

He then moved to a registrar post on the professorial unit at University College Hospital (UCH), where he worked for Professor Max Rosenheim and …
Abstract IA14: Deconstructing the origins of PDAC development
Authors: Brittany Flowers, Hang Xu, Kathryn Hanson, Christina Curtis, Hannes Vogel, Laura Wood, Laura D. Attardi
Journal: Cancer Research (2020)

Abstract The TP53 gene, which encodes the p53 transcription factor, is mutated in ~75% of human pancreatic ductal adenocarcinomas (PDACs), underscoring the fundamental role of p53 as a barrier to PDAC development. Despite this critical function, however, the cellular and molecular programs through which p53 acts in pancreatic cancer suppression remain poorly understood. To gain a better understanding of the pathways through which p53 acts to suppress PDAC development, which will provide key insight into how the disease develops, we have taken combined mouse genetic and genomic approaches. First, we have sought to determine whether p53 acts in acinar and/or ductal cells to restrain PDAC development. Importantly, for these experiments we have used adult mice to more accurately mimic the development of PDAC in humans. Second, we have sought to systematically deconstruct the role of p53 deletion and p53 missense mutations in driving cancer from these different cells of origin. This comprehensive analysis of large adult mouse cohorts has helped to define the cell of origin for PDAC and the effects of different p53 mutations on spontaneous PDAC development. To gain additional insight into the programs that become dysregulated during pancreatic cancer development, we have performed RNA-sequencing analysis on tumors arising from different compartments and driven by different genetic lesions. These studies have revealed the molecular profiles of tumors arising from acinar versus ductal cells as well those driven by different types of p53 mutations. Through comparison to human pancreatic cancer data, our studies are helping us to better understand the paths to PDAC development in humans and the underlying origins of different subtypes of this disease. Citation Format: Brittany Flowers, Hang Xu, Kathryn Hanson, Christina Curtis, Hannes Vogel, Laura Wood, Laura D. Attardi. Deconstructing the origins of PDAC development [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr IA14.
Assessing the accuracy of automatic speech recognition for psychotherapy
Authors: Adam S. Miner, Albert Haque, Jason A. Fries, Scott L. Fleming, Denise E. Wilfley, G. Terence Wilson, Arnold Milstein, Dan Jurafsky, Bruce A. Arnow, W. Stewart Agras, Li Fei-Fei, Nigam H. Shah
Journal: npj Digital Medicine (2020)

Abstract Accurate transcription of audio recordings in psychotherapy would improve therapy effectiveness, clinician training, and safety monitoring. Although automatic speech recognition software is commercially available, its accuracy in mental health settings has not been well described. It is unclear which metrics and thresholds are appropriate for different clinical use cases, which may range from population descriptions to individual safety monitoring. Here we show that automatic speech recognition is feasible in psychotherapy, but further improvements in accuracy are needed before widespread use. Our HIPAA-compliant automatic speech recognition system demonstrated a transcription word error rate of 25%. For depression-related utterances, sensitivity was 80% and positive predictive value was 83%. For clinician-identified harm-related sentences, the word error rate was 34%. These results suggest that automatic speech recognition may support understanding of language patterns and subgroup variation in existing treatments but may not be ready for individual-level safety surveillance.
Diagnosis and management of the drug hypersensitivity reactions in Coronavirus disease 19: An EAACI Position Paper
Authors: Aslı Gelincik, Knut Brockow, Gülfem E. Çelik, Inmaculada Doña, Cristobalina Mayorga, Antonino Romano, Özge Soyer, Marina Atanaskovic‐Markovic, Annick Barbaud, Maria Jose Torres
Journal: Allergy (2020)

Coronavirus disease 2019 (COVID-19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID-19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off-label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings together all the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off-label drugs and highlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactions in the course of the disease.
Abstract B50: HnRNP A3 regulates the nuclear EGFR localization and cancer progression
Authors: Chi-Yuan Chen, Yu-Han Lin, Tong-Hong Wang, Chih-Ching Wu
Journal: Cancer Research (2020)

Abstract Aberrant subcellular translocation and distribution of epidermal growth factor receptor (EGFR) represents a major yet underappreciated cancer development mechanism in non-small cell lung cancer (NSCLC). In this study, we investigated the subcellular interactome of EGFR by free labeling approaches combined with LC-MS/MS, aiming to understand the associated protein networks involved in the tumorigenesis of NSCLC. A total of 54, 77, and 63 EGFR-interacting proteins were identified specifically in the cytosol, mitochondria, and nucleus fractions, respectively. Pathway-wise analyses of these proteins using the KEGG database revealed that the proteins interacting with cytosolic and nuclear EGFR proteins are involved in pathways of ribosome and spliceosome, respectively. The EGFR-interacting proteins in mitochondria are involved in the metabolism of propanoate, fatty acid, valine, leucine, and isoleucine. One of the nuclear EGFR-interacting proteins, hnRNP A3, was shown in this work to modulate the accumulation of nuclear EGFR. Downregulation of hnRNP A3 reduced the nuclear EGFR accumulation and was accompanied with reduced tumor growth ability both in vitro and in vivo. These results suggest that variations in the subcellular translocation and distribution of EGFR within NSCLC cells could affect tumor progression. Citation Format: Chi-Yuan Chen, Yu-Han Lin, Tong-Hong Wang, Chih-Ching Wu. HnRNP A3 regulates the nuclear EGFR localization and cancer progression [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B50.
Association of Naturalistic Administration of Cannabis Flower and Concentrates With Intoxication and Impairment
Authors: L. Cinnamon Bidwell, Jarrod M. Ellingson, Hollis C. Karoly, Sophie L. YorkWilliams, Leah N. Hitchcock, Brian L. Tracy, Jost Klawitter, Cristina Sempio, Angela D. Bryan, Kent E. Hutchison
Journal: JAMA Psychiatry (2020)

The rapidly growing legal cannabis market includes new and highly potent products, the effects of which, to our knowledge, have not previously been examined in biobehavioral research studies because of federal restrictions on cannabis research.
Abstract B15: Circulating tumor cells express tissue specific antigens in multiple cancers
Authors: Dadasaheb Akolkar, Revati Patil, Darshana Patil, Pradip Fulmali, Pooja Fulmali, Shoeb Patel, Pradip Devhare, Akshay Ainwale, Vineet Datta, Cynthe Sims, Ajay Srinivasan, Rajan Datar
Journal: Clinical Cancer Research (2020)

Abstract Definitive diagnosis of solid organ cancers is based on histopathologic analysis of tumor tissue obtained by invasive biopsies. However, invasive biopsies are associated with procedural expenses, sequelae, and risks. Though immunocytochemistry (ICC) profiling of circulating tumor cells (CTCs) has been previously attempted for diagnosis in some cancers, they have been unviable due to limited yields of CTCs. We used a novel approach for enrichment of sufficient viable CTCs that permit meaningful ICC profiling for diagnosis of cancers in suspected cases. We obtained 15 mL of venous blood draw from 965 patients with confirmed diagnosis of various solid organ cancers. CTCs were enriched from PBMCs fraction using an epigenetically activated enrichment process that is lethal towards normal (nonmalignant) cells but confers survival privilege on apoptosis-resistant CTCs. Harvested CTCs were confirmed by immunostaining for EpCAM and pan-CK. Deep ICC profiling of these CTCs was performed with organ-specific marker for various organs such as lungs (TTF-1 or Napsin), breast (GCDFP15 or GATA3), ovarian (CA125 or WT-1), pancreatic (CK19 or CA19-9), cervical (P63), liver (Hep Par-1 or Glypican), colorectal (CK20 or CDX-2), head and neck (P63), kidney (Pax-8 or RCC), and prostate (PSMA or AMACR). CTCs (EpCAM+, pan-CK+) could be obtained from 94.4% of all samples. Organ-specific markers were positive in 100% of lung cancer, 79.3% of breast cancers, 70.0% of ovarian cancers, 93.3% of pancreatic cancers, 100% of cervical cancers, 61% of hepatocellular carcinomas, 92.6% ofcColorectal cancers, 98.8% of head and neck cancers, 100% of renal cancers, and 100% of prostate cancers. Our results show that deep ICC profiling of CTCs can determine tissue of origin in solid organ cancers noninvasively to substitute conventional procedures dependent on tissue extraction. Citation Format: Dadasaheb Akolkar, Revati Patil, Darshana Patil, Pradip Fulmali, Pooja Fulmali, Shoeb Patel, Pradip Devhare, Akshay Ainwale, Vineet Datta, Cynthe Sims, Ajay Srinivasan, Rajan Datar. Circulating tumor cells express tissue specific antigens in multiple cancers [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B15.
Divergence, Convergence, and Therapeutic Implications: A Cell Biology Perspective of C9ORF72-ALS/FTD
Authors: Xiaoqiang Tang, Arturo Toro, Sahana T.G., Junli Gao, Jessica Chalk, Björn E. Oskarsson, Ke Zhang
Journal: Molecular Neurodegeneration (2020)

Abstract Ever since a GGGGCC hexanucleotide repeat expansion mutation in C9ORF72 was identified as the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), three competing but nonexclusive hypotheses to explain how this mutation causes diseases have been proposed and are still under debate. Recent studies in the field have tried to understand how the repeat expansion disrupts cellular physiology, which has suggested interesting convergence of these hypotheses on downstream, functional defects in cells, such as nucleocytoplasmic transport disruption, membrane-less organelle defects, and DNA damage. These studies have not only provided an integrated view of the disease mechanism but also revealed novel cell biology implicated in neurodegeneration. Furthermore, some of the discoveries have given rise to new ideas for therapeutic development. Here, we review the research progress on cellular pathophysiology of C9ORF72-mediated ALS and FTD and its therapeutic implication. We suggest that the repeat expansion drives pathogenesis through a combination of downstream defects, of which some can be therapeutic targets.
Nectin-2 Expression on Malignant Plasma Cells Is Associated with Better Response to TIGIT Blockade in Multiple Myeloma
Authors: Ester Lozano, Mari-Pau Mena, Tania Díaz, Beatriz Martin-Antonio, Sheila León, Luis-Gerardo Rodríguez-Lobato, Aina Oliver-Caldés, Maria Teresa Cibeira, Joan Bladé, Aleix Prat, Laura Rosiñol, Carlos Fernández de Larrea
Journal: Clinical Cancer Research (2020)

T-cell immunoreceptor with Ig and ITIM domain (TIGIT) blockade could represent an alternative therapeutic option to release the immune response in patients with multiple myeloma. Here we analyzed the expression of TIGIT and its ligands poliovirus receptor (PVR) and nectin-2 in the bone marrow (BM) of patients with monoclonal gammopathies and the efficacy of TIGIT blockade activating antimyeloma immunity.Expression levels of TIGIT and its ligands were characterized by flow cytometry and ELISA. TIGIT blockade was analyzed in in vitro functional assays with peripheral T cells. BM cells were studied with NanoString technology, real-time PCR, and ex vivo patient BM cell models.TIGIT and its ligands are highly expressed in the BM of patients with multiple myeloma, suggesting that may play a role in restraining immune activation. TIGIT blockade depleted FoxP3+ Tregs while increasing proliferation of IFNγ-producing CD4+ T cells from patients with multiple myeloma. PVR ligation inhibited CD8+ T-cell signaling and cell proliferation which could be overcome with anti-TIGIT mAb. However, BM cells showed a remarkable heterogeneity in immune signature. Accordingly, functional ex vivo BM assays revealed that only some patients respond to checkpoint blockade. Thus, response to TIGIT blockade correlated with low frequency of TIGIT+ cells and high nectin-2 expression on malignant plasma cells.TIGIT blockade efficiently reinvigorated peripheral T cells from patients with multiple myeloma. However, in the BM, the efficacy of blocking anti-TIGIT mAb to achieve tumor cell death may depend on the expression of TIGIT and nectin-2, becoming potential predictive biomarkers for identifying patients who may benefit from TIGIT blockade.