tbuckley/cabot-search huggingface dataset:
Global and regional burden of interstitial lung disease and pulmonary sarcoidosis from 1990 to 2019: results from the Global Burden of Disease study 2019
Authors: Xiaoqian Ma, Lili Zhu, Jonathan S Kurche, Huijuan Xiao, Huaping Dai, Chen Wang
Journal: Thorax (2021)

Background Interstitial lung disease (ILD) and pulmonary sarcoidosis are common respiratory diseases with a heterogeneous distribution worldwide. The global burden and temporal trends of ILD and sarcoidosis are rarely explored. Methods Using the classification ‘ILD and pulmonary sarcoidosis’ from the Global Burden of Disease 2019 dataset, we described the age-standardised rates of incidence, mortality, disability-adjusted life-years (DALYs), and their average annual percentage change from 1990 to 2019 by sex, Sociodemographic Index (SDI) and region. Results In 2019, the global incidence and mortality of ILD and pulmonary sarcoidosis were 24.2 million and 169 833 cases, respectively. From 1990 to 2019, the global incidence, deaths and DALYs due to ILD and pulmonary sarcoidosis increased by 118.6%, 166.63% and 122.87% respectively. The global incidence of ILD and pulmonary sarcoidosis was higher in men and was mainly concentrated among persons aged 70‒79 of both sexes. Significant regional differences could be seen in the disease burden of ILD and pulmonary sarcoidosis: since 2006, high-SDI regions had higher age-standardised incidence rates but lower age-standardised death rates compared with the low-SDI regions. Conclusions Our study suggests the incidence, mortality and DALYs from ILD and pulmonary sarcoidosis are increasing globally. To reduce the ongoing burden of this condition, early diagnosis and treatment are vital, and more targeted and specific strategies should be established in high-burden regions. Differences in incidence and mortality across regions may reflect the influence of genetic, environmental, diagnostic, pharmacotherapeutic, and health system factors.
Differential requirement for the Polycomb repressor complex 2 in dendritic cell and tissue-resident myeloid cell homeostasis
Authors: Yifan Zhan, Yuxia Zhang, Shengbo Zhang, Hannah Coughlan, Pedro L. Baldoni, Nicolas Jacquelot, Wang H.J. Cao, Simon Preston, Cynthia Louis, Jai Rautela, Marc Pellegrini, Ian P. Wicks, Warren S. Alexander, Leonard C. Harrison, Andrew M. Lew, Gordon K. Smyth, Stephen L. Nutt, Michaël Chopin
Journal: Science Immunology (2021)

PRC2 is essential for the self-renewal of tissue-resident macrophages but dispensable for dendritic cell development and function.
Belonging in STEM: an interactive, iterative approach to create and maintain a diverse learning community
Authors: Marina J. Ayala, Javan K. Carter, Avani S. Fachon, Samuel M. Flaxman, Michael A. Gil, Heather V. Kenny, Zachary M. Laubach, Sage A. Madden, Molly T. McDermott, Angela Medina-García, Rebecca J. Safran, Ellen Scherner, Drew R. Schield, Sabela Vasquez-Rey, Julie Volckens
Journal: Trends in Ecology & Evolution (2021)
P14.18 Patient and Public Involvement to define patient-centred outcomes from National Cancer Datasets
Authors: L Pakzad-Shahabi, C Cherrington, N Brassil, P Even, D Gardner, W Fulcher, K Le Calvez, R Mauricaite, M Williams
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND GlioCova uses linked national cancer data on all 51 000 adult patients with a primary brain tumour in England (2013 - 2018) to understand patterns of care, treatment, and outcomes in patients with glioma (http://wwwf.imperial.ac.uk/blog/gliocova/). A key aim is the use of patient and carer input in defining patient-centered outcomes. We have held multiple Patient &amp; Public Involvement (PPI) sessions with patients and carergivers and data analysts to understand what patient and caregivers want to know about brain tumours. MATERIAL AND METHOD We used a modified Delphi method. The online PPI sessions (Zoom) consisted of two presentations, open discussions, and Q&amp;As. We made the sessions as interactive as possible by using Mentimeter and an interactive online white board (Explain Everything). Pre-reading material was circulated via email. Attendees (6–14 per session) covered a wide range of ages (30–75), diagnoses (GBM, recurrent gliomas, low grade gliomas, ependymoma); patients, caregivers, neuro-oncology staff, data analysts and basic scientists. Work was conducted in line with the INVOLVE PPI guidance. RESULTS We identified four questions that were of interest to patients and had correlates in the data: Patients and caregivers were also interested in the impact of diet, quality of life, social life, and exercise. However, these data cannot be answered using the current national data. CONCLUSION Our PPI work has helped us to identify and prioritise questions to ask of the data. Ongoing PPI work will provide a wider perspective and identify knowledge gaps for future research. Patients and caregivers report feeling empowered, being part of a team, feeling like they had given something back and done something meaningful for the research community and other patients. Patients and caregivers also felt that they had an enriched understanding of the data that is collected. As this process is an iterative process, we will hold more PPI sessions to identify and prioritise topics to analyse.
"INFLAMMATORY RESPONSES TO THE OCCUPATIONAL INHALATION OF METAL FUME". K.T. PALMER, R.M.C. MCNEILL LOVE, J.R. POOLE, D. COGGON, A.J. FREW, C.H. LINAKER AND J.K. SHUTE. EUR RESPIR J 2006; 27: 366-373.
Journal: European Respiratory Journal (2007)
P14.93 Partial stiff-person syndrome, cerebral lymphoma, and HIV infection
Authors: R Ivan, B Cîrciumaru, C M Poșircă, C A Sîrbu
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Stiff person syndrome (SPS) is a rare entity, characterized by rigidity or stiffness of the muscles. It is usually autoimmune, but it can also appear as a paraneoplastic (5%) or cryptogenic disorder. This study aims to establish a potential connection between what appears to be a partial SPS, an advanced HIV infection, and a primary central nervous system (CNS) lymphoma in a young adult. MATERIAL AND METHODS We present the case of a 42-year-old male, who, in the course of approximately five months developed dizziness, impairment of manual dexterity, ataxia, postural instability, hallucinations, weight loss, and fever. He was admitted to our clinic, after a progressive deterioration of his mental status, presenting global aphasia, and increased left hemibody muscle tone, with persistent left torticollis. According to the blood tests and cerebral MRIs he was diagnosed with HIV infection, thrombophilia, and a left frontal mass, of unknown etiology. RESULTS His neurocognitive deterioration was suggestive of a primary CNS lymphoma and the ipsilateral abnormal increased muscular tone raised the suspicion of a partial SPS. It appeared most likely in the context of the brain lesion, even if its nature remained unknown, due to the deteriorated status, that made biopsy impossible. The diagnosis of cerebral lymphoma was based on the IRM characteristics and the change in appearance after corticosteroid therapy. CONCLUSION Even if it represents a rare diagnosis, partial SPS can appear as a paraneoplastic entity, our patient’s evolution and clinical examination being suggestive for this pathology.
Synthetic Retinoids Beyond Cancer Therapy
Authors: Lorraine J. Gudas
Journal: The Annual Review of Pharmacology and Toxicology (2021)

While the uses of retinoids for cancer treatment continue to evolve, this review focuses on other therapeutic areas in which retinoids [retinol (vitamin A), all- trans retinoic acid (RA), and synthetic retinoic acid receptor (RAR)α-, β-, and γ-selective agonists] are being used and on promising new research that suggests additional uses for retinoids for the treatment of disorders of the kidneys, skeletal muscles, heart, pancreas, liver, nervous system, skin, and other organs. The most mature area, in terms of US Food and Drug Administration–approved, RAR-selective agonists, is for treatment of various skin diseases. Synthetic retinoid agonists have major advantages over endogenous RAR agonists such as RA. Because they act through a specific RAR, side effects may be minimized, and synthetic retinoids often have better pharmaceutical properties than does RA. Based on our increasing knowledge of the multiple roles of retinoids in development, epigenetic regulation, and tissue repair, other exciting therapeutic areas are emerging.
The gut, its microbiome, and the brain: connections and communications
Authors: Michael D Gershon, Kara Gross Margolis
Journal: Journal of Clinical Investigation (2021)

Modern research on gastrointestinal behavior has revealed it to be a highly complex bidirectional process in which the gut sends signals to the brain, via spinal and vagal visceral afferent pathways, and receives sympathetic and parasympathetic inputs. Concomitantly, the enteric nervous system within the bowel, which contains intrinsic primary afferent neurons, interneurons, and motor neurons, also senses the enteric environment and controls the detailed patterns of intestinal motility and secretion. The vast microbiome that is resident within the enteric lumen is yet another contributor, not only to gut behavior, but to the bidirectional signaling process, so that the existence of a microbiota-gut-brain “connectome” has become apparent. The interaction between the microbiota, the bowel, and the brain now appears to be neither a top-down nor a bottom-up process. Instead, it is an ongoing, tripartite conversation, the outline of which is beginning to emerge and is the subject of this Review. We emphasize aspects of the exponentially increasing knowledge of the microbiota-gut-brain “connectome” and focus attention on the roles that serotonin, Toll-like receptors, and macrophages play in signaling as exemplars of potentially generalizable mechanisms.
Art in Endoscopy: Moai Monolith Mysteries
Authors: Gertjan Rasschaert
Journal: Endoscopy (2021)

A patient with significant aortic valve stenosis underwent esophagogastroduodenoscopy (EGD) with routine biopsies. Subsequently there was a decrease in hemoglobin, and repeat EGD exposed this fascinating image resembling an Easter Island Moai statue. The true meaning and appearance of these statues is still heavily debated by archeologists worldwide. Just like the monoliths, the exact origin of the ulcer proved mysterious. An enthusiastic biopsy possibly coupled with a mechanism similar to Heyde’s syndrome evoked this elegant yet enigmatic clot. In Heyde’s syndrome, the combination of shear stress and cleavage by the ADAMTS13 enzyme makes von Willebrand factor hemostatically less competent. Hemostasis of this oozing ulcer was obtained after bipolar electrocoagulation.
Covid-19: Long covid must be recognised as occupational disease, says BMA
Authors: Elisabeth Mahase
Journal: BMJ (2021)

The UK government must recognise long covid as an occupational disease and invest in its monitoring, research, and treatment, doctors have said.

In a motion passed at the BMA annual representative meeting, doctors called on the body to “seek the recognition of occupationally acquired acute covid and long covid in doctors as an occupational disease.” They also called for a multidisciplinary approach to the management of long covid that includes primary, specialist, and occupational medicine.

GP Amy Small, who proposed the motion, …
P14.58 Efficacy and safety of lomustine versus fotemustine as first and second line treament in relapsed glioblastoma patients
Authors: M Domènech, C Fabregat, A Hernández, S del Barco, C Panciroli, D Garcia-Illescas, M Vieito, N Vilariño, C Mesia, C Balañà
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioblastoma (GB) is the most aggressive primary brain tumour. Despite the survival benefit associated with adjuvant therapy, most of patients (pts) relapse after initial therapy. Nitrosoureas (NU) are the standard treatment at relapse in Europe. Both fotemustine (FM) (Addeo schema) and lomustine (LM) (administered orally every 6 weeks) are used in this context. MATERIAL AND METHODS This retrospective cohort study included pts diagnosed with GB treated with NU at relapse in four Catalonia hospitals from 2010 to 2020. Clinical and pathological data were collected from medical records. We analysed 6months-progression-free survival (6m-PFS), progression-free survival (PFS) and overall survival (OS) from the start of NU to progression or death respectively. Differences in toxicity grade using CTCAE v5.0 were analysed globally as ‘non-toxicity’, ‘mild toxicity (grade 1 or 2)’ and ‘high toxicity (grade 3 or 4)’. RESULTS We identified 236 GB pts with a median age of 58 years old. 29% of the pts presented MGMT promotor methylation and only 3%(n=7) had IDH mutation. After a median follow-up of 20 months, 94% of the pts were dead at the time of the analyses. At first line, 83 pts were treated with FM and 18 with LM. Pts treated with FM had better performance status (PS) than those treated with LM (p=.010). Median PFS was 2 months and 6m-PFS was 12% vs 6% in FM and LM group respectively (p=.87). Median OS was 3 months with LM vs 6 months with FM, with no statistically significant differences even adjusted for prognostic factors (p=.79 HR:0.9 CI 95% 0.41–1.96).At second line, 78 were treated with FM and 24 with LM, no differences between groups. Median PFS was 2 months in both groups and median OS was 3 vs 5 months for pts treated with LM vs FM respectively, with no significant differences. 6m-PFS was 13% for LM vs 0% for the FM group (p=.39).Pts received a mean of 1.7 cycles (every 6 weeks) and 4.1 cycles (every 2 weeks) in LM and FM group, respectively. Thrombocytopenia was the most common serious side-effect, with a higher proportion of grade 1–2 toxicity in the FM group (p=.03) that also required more treatment delays (p=.01). CONCLUSION Despite being retrospective study and a few pts were treated with LM, there were no differences neither in PFS nor in OS in pts treated with LM vs FM at first or second line. Higher G1-2 thrombocytopenia was shown in the FM group probably due to a higher number of hematology samples collected.
Covid-19 vaccines for teenagers: conversations and consent
Authors: Sonia Saxena, Helen Skirrow, Helen Bedford, Kate Wighton
Journal: BMJ (2021)

On 13 September, the UK chief medical officers recommended that all 12-15 year olds be offered a single dose of Pfizer-BioNTech covid-19 vaccine. 1 This followed a previous recommendation by the Joint Committee on Vaccination and Immunisation 2 not to offer covid-19 vaccines to healthy 12-15 year olds.The UK now joins a growing list of countries offering vaccination to those aged 12 and over, but it is providing only one dose rather than the two given in other countries because of concerns about rare side effects such as heart inflammation.
Self-Cognizant Bionic Liquid Sensor for Pathogen Diagnosis
Authors: B. Fong
Journal: Cyborg and Bionic Systems (2021)

As observed in the outbreaks of SARS and swine flu, as well as many other infectious diseases, the huge volume of human traffic across numerous enclosed public venues has posed immense challenges to preventing the spread of communicable diseases. There is an urgent need for effective disease surveillance management in public areas under pandemic outbreaks. The physicochemical properties associated with ionic liquids make them particularly suited for molecular communications in sensing networks where low throughput is quite adequate for pathogen detection. This paper presents a self-cognizant system for rapid diagnosis of infectious disease using a bionic sensor such that testing can be supported without collecting a fluid sample from a subject through any invasive methods. The system is implemented for testing the performance of the proposed bionic liquid sensing network.
Abstract 13587: Combined Ranolazine and Dofetilide or Ranolazine and Sotalol in the Management of Atrial Fibrillation
Authors: Sarfaraz Memon, Sonal Pruthi, Jeffrey Kluger
Journal: Circulation (2019)

Introduction: Ranolazine, an inhibitor of late-phase sodium current (INA) has been shown to reduce atrial fibrillation (AF) burden. HARMONY trial showed that the combination of ranolazine to dronad...
Endocannabinoid-Based Therapies
Authors: Daniele Piomelli, Alex Mabou Tagne
Journal: The Annual Review of Pharmacology and Toxicology (2021)

The endocannabinoids are lipid-derived messengers that play a diversity of regulatory roles in mammalian physiology. Dysfunctions in their activity have been implicated in various disease conditions, attracting attention to the endocannabinoid system as a possible source of therapeutic drugs. This signaling complex has three components: the endogenous ligands, anandamide and 2-arachidonoyl- sn-glycerol (2-AG); a set of enzymes and transporters that generate, eliminate, or modify such ligands; and selective cell surface receptors that mediate their biological actions. We provide an overview of endocannabinoid formation, deactivation, and biotransformation and outline the properties and therapeutic potential of pharmacological agents that interfere with those processes. We describe small-molecule inhibitors that target endocannabinoid-producing enzymes, carrier proteins that transport the endocannabinoids into cells, and intracellular endocannabinoid-metabolizing enzymes. We briefly discuss selected agents that simultaneous-ly interfere with components of the endocannabinoid system and with other functionally related signaling pathways.
Macrophage MST1/2 Disruption Impairs Post-Infarction Cardiac Repair via LTB4
Authors: Mingming Liu, Meng Yan, Jinlong He, Huizhen Lv, Zhipeng Chen, Liyuan Peng, Wenbin Cai, Fang Yao, Chen Chen, Lei Shi, Kai Zhang, Xu Zhang, Dao-Wen Wang, Li Wang, Yi Zhu, Ding Ai
Journal: Circulation Research (2021)

Rationale: Timely inhibition of inflammation and initiation of resolution are important to repair injured tissues. MST1/2 (mammalian STE20-like protein kinase 1/2) acts as a regulator of macrophage-associated immune responses to bacterial infections. However, the role of MST1/2 in regulating macrophage phenotype and function in myocardial infarction (MI) remains unclear. Objective: To determine the function and underlying mechanism of macrophage MST1/2 in cardiac repair post-MI. Methods and Results: Using LysMCre -mediated Mst1/2 -deficient mice, we found that MST1 deficiency exacerbated cardiac dysfunction after MI. Single-cell RNA sequencing assay indicated that the effect was attributed to a shift of macrophage subtypes from those expressing Cxcl2 and Cd163 toward Ccl2 and Ccl4 expression. Mass spectrometry identified LTB4 (leukotriene B4) as the lipid mediator that was upregulated in the absence of MST1. We found that MST1 phosphorylated 5-LOX (5-lipoxygenase) at its T218 residue, disrupting the interaction between 5-LOX and 5-LOX-activating protein, resulting in a reduction of LTB4 production. In contrast, a 5-LOX T218A variant showed no response to MST1. Moreover, treatment of peritoneal macrophages with LTB4 or medium conditioned by Mst1 -deficient macrophages resulted in high Ccl2 and Ccl4 expression and low Cxcl2 and Cd163 expression, except when the cells were co-treated with the BLT1 (LTB4 receptor 1) antagonist CP105696. Furthermore, CP105696 ameliorated cardiac dysfunction in LysMCre -mediated Mst1/2 -deficient mice and enhanced cardiac repair in wild-type mice treated with XMU-MP-1 (4-((5,10-dimethyl-6-oxo-6,10-dihydro-5H-pyrimido[5,4-b]thieno[3,2-e][1,4]diazepin-2-yl)amino)benzenesulfonamide) after MI. Conclusions: Taken together, our results demonstrate that inhibition of MST1/2 impaired post-MI repair through activating macrophage 5-LOX–LTB4–BLT1 axis.
When oncology care goes digital: A closer look at disparities.
Authors: Jad Habouch, Adit Mane
Journal: Journal of Clinical Oncology (2021)

119 Background: Oncology providers are increasingly integrating digital solutions, such as patient relationship management (PRM), to improve patient care. PRM enables patients to communicate with their clinic, view health records, receive educational materials and submit patient-reported outcomes (ePROs). However, disparities in PRM adoption and engagement in oncology care are unclear. Methods: Patients with cancer aged ≥18 years at first appointment between Oct 2017-Sep 2020 with ≥6 months’ follow-up, regardless of tumor type, line of therapy or diagnosis date, were selected from 77 US oncology clinics. Patients’ demographics, login history and digital activity data were sourced from the clinics’ PRM (Navigating Cancer). Chi-square analyses identified statistically significant differences by race/ethnicity. Results: 202,345 patients were identified as White (78%), Black (11%), Hispanic (8%), Asian/Pacific Islander (PI)/Native Hawaiian (NH; 2%) and American Indian (AI)/Alaska Native (AN; 1%) (Table). Of these, 85,020 (42%) had digital access (≥2 valid PRM logins) ranging from 46% (White) to 21% (Hispanic). Similar proportions of White, Asian/PI/NH and Hispanic patients were digitally active for 6 months (8%-13%), while Black patients lagged behind at 5% ( P&lt;0.0001). Digital education completion, which required a patient to read all assigned materials, ranged from 26% (AI/AN) to 14% (Asian/PI/NH). Surpassing other patient groups, 32% of AI/AN patients reported symptoms via phone, followed by 16% of White patients. ePROs submission rates were 5 times higher than rates of symptom reporting via phone for all groups except AI/AN. Conclusions: This study demonstrated that White patients have higher digital access rates compared with other racial/ethnic patient groups, especially Hispanic and Black patients. Further evaluation of digital health components depicted disparities in digital, phone and ePROs engagement for all groups, except AI/AN patients, who invariably had higher engagement. No differences were observed in ePROs access. Further, disparities observed in symptoms reporting via phone were larger than the disparities seen in ePROs submissions. More studies are needed to assess other determinants of digital health disparities.[Table: see text]
Early Outcomes Following off-Pump Coronary Artery Bypass Surgery under General Anaesthesia with and without High Thoracic Epidural Analgesia: A Comparative Study
Authors: Chaitali Dasgupta
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Introduction: Reduction of postoperative morbidity by providing optimal pain relief and improving overall quality of care is an important goal of modern anaesthesia practice. The aim of this prospective, randomized, open, controlled study is to investigate the impact of high thoracic epidural analgesia on early clinical outcomes in patients undergoing off-pump coronary artery bypass (OPCAB) surgery. Methodology: After obtaining the institutional ethics committee approval and written informed consent from all patients, 80 patients of either sex, aged 40 – 70 years, scheduled for elective primary OPCAB surgery were randomized into two groups. Group I received 4 mL of an epidural bolus of 1% ropivacaine and fentanyl 100 µg followed by ropivacaine 1% and fentanyl 5 µg/mL infusion for 72 h at 3–5 mL/h postoperatively. Analgesia in the Group II was provided with a continuous IV fentanyl infusion. Patients were given rescue analgesic (inj Tramadol intravenous) when VAS score is &gt;40 in the postoperative period. Results: VAS score, need for rescue analgesics and incidence of postoperative arrythmia were significantly lower in Group I specially for first twenty four hours postoperatively. Time for extubation and length of postoperative ICU stay were found similar in both the groups. Incidence of other outcomes found to be not significant. Conclusion: The pain scores, analgesic requirements and incidence perioperative arryrhmias were significantly less in Group I compared to Group II, but we could not be able to find any significant difference in time for extubation and length of ICU stay, neither in incidence of postoperative MI, CVA, renal failure, blood transfusion and death.