tbuckley/cabot-search huggingface dataset:
A map of transcriptional heterogeneity and regulatory variation in human microglia
Authors: Adam M. H. Young, Natsuhiko Kumasaka, Fiona Calvert, Timothy R. Hammond, Andrew Knights, Nikolaos Panousis, Jun Sung Park, Jeremy Schwartzentruber, Jimmy Liu, Kousik Kundu, Michael Segel, Natalia A. Murphy, Christopher E. McMurran, Harry Bulstrode, Jason Correia, Karol P. Budohoski, Alexis Joannides, Mathew R. Guilfoyle, Rikin Trivedi, Ramez Kirollos, Robert Morris, Matthew R. Garnett, Ivan Timofeev, Ibrahim Jalloh, Katherine Holland, Richard Mannion, Richard Mair, Colin Watts, Stephen J. Price, Peter J. Kirkpatrick, Thomas Santarius, Edward Mountjoy, Maya Ghoussaini, Nicole Soranzo, Omer A. Bayraktar, Beth Stevens, Peter J. Hutchinson, Robin J. M. Franklin, Daniel J. Gaffney
Journal: Nature Genetics (2021)
AB0295 TREATMENT OF HIGH RISK/REFRACTORY OBSTETRIC ANTIPHOSPHOLIPID SYNDROME. A SINGLE CENTRE EXPERIENCE
Authors: A. Hoxha, P. Marson, M. Favaro, M. Tonello, M. Zen, T. Del Ross, A. Calligaro, A. Ruffatti
Journal: Annals of the Rheumatic Diseases (2021)

Background: The most efficacious strategy to manage pregnant patients with antiphospholipid syndrome (APS) who are at high risk of adverse pregnancy outcomes ± refractory to conventional heparin/low-dose aspirin treatment is currently unknown (1, 2). Objectives: The purposes of this study were to investigate the efficacy and safety of a second-line treatment protocol administered in addition to twice daily low molecular weight heparin and low-dose aspirin to pregnant patients affected with high-risk ± refractory primary APS. Methods: Patients were included in the study if satisfying the following criteria were: 1) the presence of triple antiphospholipid antibody positivity (IgG/IgM anticardiolipin + IgG/IgM anti-β2 Glycoprotein I antibodies + lupus anticoagulant), 2) previous thrombosis and/or a history of one or more early and severe pregnancy complications. The second-line treatment protocol included weekly plasmapheresis or immunoadsorption and fortnightly 1g/kg intravenous immunoglobulins. Results: Twenty-four pregnancies occurring between 2002 and 2019 in 19 primary APS patients, (mean age 35.1 ± 3.5 SD) were monitored. Triple antiphospholipid positivity was detected in all 19 cases (100%). Seven of these women (36.8%) had a history of thrombosis, five (26.3%) one or more previous failed pregnancies associated to severe pregnancy complications and seven (36.8%) both clinical criteria. Twenty- three pregnancies (95.8%) produced live neonates (13 females and 10 males), all born between the 26 th and 38 th week of gestation (mean 33.6 ± 3.5 SD); birth weight percentile was 35.8 ± 24.1 SD and mean Apgar score at 5 min 8.7 ± 1.1 SD. Due to premature birth (24 th week) complicated by fetal sepsis, one pregnancy (4.2%) had a negative outcome. During the treated pregnancy there were no episodes of thrombosis; there were five cases (20.8%) of severe maternal complications during pregnancy or puerperium and four of fetal complications (16.6%), all followed by complete recovery after delivery. No side-effects of the treatment were registered. Conclusion: Given the high live birth rate and the safety associated to it, the second-line treatment protocol described here could be taken into consideration when the treatment of a high-risk APS pregnancy ± refractory to conventional therapy is being evaluated. References: [1]Tektonidou MG, et al. Ann Rheum Dis 2019; 0 :1–9. doi:10.1136/annrheumdis-2019-215213 [2]Giacomelli et al. Autoimmun Rev. 2020;102738. doi.org/10.1016/j.autrev.2020.102738 Disclosure of Interests: None declared
Abstract 11959: Long Term Cardiac Arrhythmia and Chronotropic Evaluation in Severe Anorexia Nervosa (lace-an): A Pilot Study
Authors: Morteza Farasat, Ashlie Watters, Joseph Schuller, Tiffany Bendelow, Philip S Mehler, Mori J Krantz
Journal: Circulation (2019)

Background: Anorexia nervosa (AN) carries the highest risk of sudden death of all psychiatric disorders. While autonomic dysfunction and cardiac arrhythmias have been speculated as potential causes...
Advanced Practice Clinicians—Neurology’s Underused Resource
Authors: Calli L. Cook, Heidi B. Schwarz
Journal: JAMA Neurology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Epigenetic Induction of Mitochondrial Fission Is Required for Maintenance of Liver Cancer–Initiating Cells
Authors: Miaoling Tang, Meisongzhu Yang, Geyan Wu, Shuang Mo, Xingui Wu, Shuxia Zhang, Ruyuan Yu, Yameng Hu, Yingru Xu, Ziwen Li, Xinyi Liao, Jun Li, Libing Song
Journal: Cancer Research (2021)

Mitochondrial dynamics play vital roles in the tumorigenicity and malignancy of various types of cancers by promoting the tumor-initiating potential of cancer cells, suggesting that targeting crucial factors that drive mitochondrial dynamics may lead to promising anticancer therapies. In the current study, we report that overexpression of mitochondrial fission factor (MFF), which is upregulated significantly in liver cancer-initiating cells (LCIC), promotes mitochondrial fission and enhances stemness and tumor-initiating capability in non-LCICs. MFF-induced mitochondrial fission evoked mitophagy and asymmetric stem cell division and promoted a metabolic shift from oxidative phosphorylation to glycolysis that decreased mitochondrial reactive oxygen species (ROS) production, which prevented ROS-mediated degradation of the pluripotency transcription factor OCT4. CRISPR affinity purification in situ of regulatory elements showed that T-box transcription factor 19 (TBX19), which is overexpressed uniquely in LCICs compared with non-LCICs and liver progenitor cells, forms a complex with PRMT1 on the MFF promoter in LCICs, eliciting epigenetic histone H4R3me2a/H3K9ac-mediated transactivation of MFF. Targeting PRMT1 using furamidine, a selective pharmacologic inhibitor, suppressed TBX19-induced mitochondrial fission, leading to a profound loss of self-renewal potential and tumor-initiating capacity of LCICs. These findings unveil a novel mechanism underlying mitochondrial fission-mediated cancer stemness and suggest that regulation of mitochondrial fission via inhibition of PRMT1 may be an attractive therapeutic option for liver cancer treatment. SIGNIFICANCE: These findings show that TBX19/PRMT1 complex-mediated upregulation of MFF promotes mitochondrial fission and tumor-initiating capacity in liver cancer cells, identifying PRMT1 as a viable therapeutic target in liver cancer.
Recent Developments in Nanomaterial‐Based Shear‐Sensitive Drug Delivery Systems
Authors: Yi Wang, Avani V. Pisapati, X. Frank Zhang, Xuanhong Cheng
Journal: Advanced Healthcare Materials (2021)

Abstract Nanomaterial‐based drug delivery systems (DDSs) increase the efficacy of various therapeutics, and shear stress has been shown to be a robust modulator of payload release. In the past few decades, a deeper understanding has been gained of the effects of flow in the body and its alteration in pathological microenvironments. More recently, shear‐responsive nanomaterial DDSs have been developed. Studies on this subject mainly from the last decade are reviewed here, focusing on innovations of the material design and mechanisms of the shear response. The two most popular shear‐controlled drug carriers distinguished by different release mechanisms, that is, shear‐deformable nanoparticles (NPs) and shear‐dissociated NP aggregates (NPAs), are surveyed. The influence of material structures on their properties such as drug loading, circulation time, and shear sensitivity are discussed. The drug development stages, therapeutic effects, limitations, and potential of these DDSs are further inspected. The reviewed research emphasizes the advantages and significance of nanomaterial‐based shear‐sensitive DDSs in the field of targeted drug delivery. It is also believed that efforts to rationally design nanomaterial DDSs responsive to shear may prompt a new class of diagnostics and therapeutics for signaling and rectifying pathological flows in the body.
New GP patient data extraction scheme raises concern
Authors: Adrian O’Dowd
Journal: BMJ (2021)

A new way to extract patients’ data from general practices in England has been criticised by privacy rights campaigning groups, which are concerned about the scheme’s lack of clarity and the level of detailed information being gathered.

However, medical profession representatives seem to broadly support the approach, although they agree that more needs to be done to clarify its purposes so it can secure public support.

Details were given on 12 May of the new GP data collection system for England, titled General Practice Data for Planning and Research (GPDPR), which goes live on 1 July and from which patients can choose to opt out by 23 June.1 It will replace the current GP Extraction Service (GPES).

Under the new scheme NHS Digital will collect data on treatments, referrals, and appointments over the past 10 years, alongside other data from medical records data for patients’ entire history. The new service is designed to enable faster access to pseudonymised data on around 55 million patients for planners and researchers.

But campaigners fear that much more data will be collected than has been attempted before, including information on mental and sexual health, criminal records, and abuse, and that the scheme is being rushed into place without …
POS0987 INFLAMMATION OF THE HIP JOINTS IN EARLY AXIAL SPONDYLOATRITIS: DATA ANALYSIS OF VISUALIZATION METHODS
Authors: E. Agafonova, T. Dubinina, A. Demina, D. Rumiantceva, S. Erdes
Journal: Annals of the Rheumatic Diseases (2021)

Background: According to epidemiological studies in Russia, the inflammation of the hip joints occurs in half of patients with ankylosing spondylitis (AS). There have been practically no studies devoted to the investigations of coxitis in patients with early axial spondyloarthritis (axSpA). It is still unknown what factors cause the development of coxitis in axSpA; there is no generally accepted algorithm for diagnosing this condition, especially at an early stage. Previous studies have shown that coxitis in patients with AS develops on average 5–10 years after the onset of the disease, some patients already have irreversible changes in the hip joint at the time of diagnosis, and some do not develop coxitis never. Objectives: To compare the clinical manifestations of coxitis with the results of magnetic resonance imaging (MRI), ultrasound (US), and radiography of the hip. Methods: We examined 175 patients (mean age 28.0 ± 5.92 years) with axSpA (ASAS, 2009), with a duration of inflammatory back pain of no more than 5 years, from the CoRSaR cohort. The median duration of the disease was 21 [3–60] months. BASDAI - 4.0 ± 2.0, BASFI - 2.0 [0.4; 3.5]. Among the included patients, 69 (39.4%) had nr-axSpA, and 106 - AS; 87% were HLA-B27 positive. All patients underwent US examination of the hip joint. When synovitis was detected, the patients underwent MRI examination of the hip joint. The increase in the cervical-capsular distance (CCD) more than 7 mm was considered as an ultrasonic coxitis. The median CCD was 7.5 [7.0; 8.2] mm. For coxitis in MRI, osteitis of the head of the hip or acetabulum and synovitis were taken. Radiographic severity of coxitis was determined by BASRI hip. Results: According to the US data, synovitis of the hip joint was detected in 54 from 175 (30.9%) patients. Pain in the hip joint had 33 (61%) patients. There was no correlation between the intensivity of pain and CCD. CCD significantly correlated with laboratory indicators of disease activity, such as ESR (r = 0.34; p &lt;0.05) and CRP (r = 0.3; p &lt;0.05). Only 7 (13.0%) patients had BASRI hip stages II or III and the rest had normal hip joints. 39 (72%) had MRI manifestations of coxitis: 36 (66%) patients had synovitis, 1 (2%) had bone marrow edema, and 2 (4%) had a combination of synovitis with osteitis. Patients with and without radiographic coxitis did not differ in terms of disease activity and functional indices. Conclusion: In early axSPA: - 30.9% of patients have hip synovitis, and among them, MRI signs of coxitis have 72%, and X-ray coxitis - 13%; - ultrasound synovitis is only confirmed by MRI in 70% of cases; - it seems that the radiological progression of coxitis does not depend on the activity of the disease. Disclosure of Interests: None declared.
A Transcriptionally Distinct Subpopulation of Healthy Acinar Cells Exhibit Features of Pancreatic Progenitors and PDAC
Authors: Vishaka Gopalan, Arashdeep Singh, Farid Rashidi Mehrabadi, Li Wang, Eytan Ruppin, H. Efsun Arda, Sridhar Hannenhalli
Journal: Cancer Research (2021)

Pancreatic ductal adenocarcinoma (PDAC) tumors can originate either from acinar or ductal cells in the adult pancreas. We re-analyze multiple pancreas and PDAC single-cell RNA-seq datasets and find a subset of nonmalignant acinar cells, which we refer to as acinar edge (AE) cells, whose transcriptomes highly diverge from a typical acinar cell in each dataset. Genes upregulated among AE cells are enriched for transcriptomic signatures of pancreatic progenitors, acinar dedifferentiation, and several oncogenic programs. AE-upregulated genes are upregulated in human PDAC tumors, and consistently, their promoters are hypomethylated. High expression of these genes is associated with poor patient survival. The fraction of AE-like cells increases with age in healthy pancreatic tissue, which is not explained by clonal mutations, thus pointing to a nongenetic source of variation. The fraction of AE-like cells is also significantly higher in human pancreatitis samples. Finally, we find edge-like states in lung, liver, prostate, and colon tissues, suggesting that subpopulations of healthy cells across tissues can exist in pre-neoplastic states. SIGNIFICANCE: These findings show "edge" epithelial cell states with oncogenic transcriptional activity in human organs without oncogenic mutations. In the pancreas, the fraction of acinar cells increases with age.
A Hopeful Leap Forward by Multicentric Cooperation for Precision-Based Therapy for Very Resistant, Relapsed, or Refractory Childhood Leukemia
Authors: Beat C. Bornhauser, Jean-Pierre Bourquin
Journal: Cancer Discovery (2021)

Abstract Summary: Pikman and colleagues report the results of a multicentric prospective clinical trial of the leukemia precision-based therapy (LEAP) consortium that combines identification of targetable lesions in drug-resistant childhood leukemia, tiered based on evidence for genomic lesions and drug target, validation of matching small-molecule targeted agents, and treatment of individual patients. The study demonstrates the impact of genomic information on disease classification, treatment guidance, and translational research, but also illustrates the challenges for target prediction and trial design for increasingly heterogeneous and smaller subgroups of patients. See related article by Pikman et al., p. 1424.
Loss of Gas7 Is a Key Metastatic Switch in Neuroblastoma
Authors: Marie J. Menard
Journal: Cancer Research (2021)

Abstract Metastatic spread to distant tissues and organs is responsible for most cancer-related mortalities. Changes in the invasiveness ability of metastatic tumor cells often come with significantly altered gene expression profiles compared with primary tumor cells. Identifying the main actors involved in the metastatic switch of tumor cells is key to proposed new therapeutic approaches. In this issue, the loss of growth-arrest specific 7 is described as one of the main events driving metastatic spread in neuroblastoma. See related article by Dong et al., p. 2995
Author Correction: Attributes and predictors of long COVID
Authors: Carole H. Sudre, Benjamin Murray, Thomas Varsavsky, Mark S. Graham, Rose S. Penfold, Ruth C. Bowyer, Joan Capdevila Pujol, Kerstin Klaser, Michela Antonelli, Liane S. Canas, Erika Molteni, Marc Modat, M. Jorge Cardoso, Anna May, Sajaysurya Ganesh, Richard Davies, Long H. Nguyen, David A. Drew, Christina M. Astley, Amit D. Joshi, Jordi Merino, Neli Tsereteli, Tove Fall, Maria F. Gomez, Emma L. Duncan, Cristina Menni, Frances M. K. Williams, Paul W. Franks, Andrew T. Chan, Jonathan Wolf, Sebastien Ourselin, Tim Spector, Claire J. Steves
Journal: Nature Medicine (2021)
POS0854 SEX DIFFERENCES IN SYSTEMIC SCLEROSIS PATIENTS IN A SINGLE CENTER IN EASTERN EUROPE
Authors: A. Petre, L. Groseanu, A. Balanescu, V. Bojinca, D. Opris-Belinski, F. Berghea, I. Saulescu, D. Mazilu, S. Daia, A. Borangiu, C. L. Constantinescu, M. Abobului, M. M. Negru, C. Cobilinschi, D. Predeteanu, R. Ionescu
Journal: Annals of the Rheumatic Diseases (2021)

Background: The low overall prevalence of systemic sclerosis (SSc) and the low proportion of male patients have resulted in a scarcity of studies assessing sex differences in SSc patients, and contradictory results have often been observed. Objectives: The aim of the study was to assess differences in disease manifestations in a cohort of SSc patients according to gender. Methods: We performed a retrospective observational study using data extract from the EULAR scleroderma trials and research (EUSTAR) cohort 096.We looked at sex influence on disease characteristics at baseline and then focused on patients with at least 2 years of follow-up to estimate the effects of sex on disease progression and survival. Results: 173 patients with SSc were available for the baseline analyses. Males were older (52,96 vs 45,88, p=0.009), were more likely to smoke (73% vs 7%, p&lt;0,001), had more frequent diffuse skin involvement (73,1% vs 56,5%,p&lt;0.01), higher modified Rodnan skin score (34,61% vs 17%, p=0.01) and activity score(84,62% vs 46,26%,p&lt;0.001) and were more often associed with positive acute phase reactants (65,38% vs 38,77%, p=0.01). Severe interstitial lung disease was more common in males (59,09% vs 27,53%, p=0.003), also the presence of tendon friction rubs was more frequent in this sex group (23,07% vs 8,84%, p=0.032). In the longitudinal analysis after a mean follow-up of 3,5(±0,65) years, male sex was associated with a higher risk of scleroderma renal crisis (OR:9.45 (1.49 to 59.69); p=0.004), digital contractures (OR:8,2 (3,1 to 21,9); p&lt;0,001), arrhythmias (OR:3,37 (1.36 to 8,34); p=0.006), pulmonary fibrosis (OR: 3.56, (1.51 to 8.41); p=0.003), pulmonary hypertension (OR: 3.01 (1.19 to 7,59); p=0.016), severe vascular involvement (OR:2,86, (1,22 to 6,73); p=0.013) and low ventricular ejection fraction (OR: 2,84, (1.2 to 6,73); p=0.014). Males had significantly reduced survival time after diagnosis (p=0,004). The most frequent causes of death were scleroderma renal crisis in males and pulmonary hypertension in females. Conclusion: Although more common in women, SSc appears as strikingly more severe in men. Our results demonstrate a higher risk of severe organ involvement and poor prognosis in men. These results raise the point of including sex in the management and the decision-making process. Disclosure of Interests: None declared
Sudden Paralysis in a 39-Year-Old Woman With Metastatic Breast Cancer
Authors: Claire Griffiths, Jennifer Connelly, Lubna N. Chaudhary
Journal: JAMA Oncology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal