tbuckley/cabot-search huggingface dataset:
POS0489 DOES TIME TO REMISSION DIFFER DEPENDING ON ROUTE OF ADMINISTRATION OF METHOTREXATE IN AN EARLY ARTHRITIS TREAT TO TARGET (T2T) COHORT?
Authors: I. Ali
Journal: Annals of the Rheumatic Diseases (2021)

Background: Rheumatoid arthritis (RA) is a multisystem inflammatory disorder that affects the joints and other body tissues. Approximately 1% of the worldwide population is living with RA 1. Methotrexate is the first line DMARD used for treatment of RA 2. Objectives: The aim of this study was to analyse MTX use in achieving remission in early arthritis patients and to compare the route of administration to see whether it affects the time interval to remission. Methods: An observational, prospective study was performed on patients’ data available from our Early Arthritis Cohort. Newly diagnosed patients with RA meeting the American College of Rheumatology (ACR) criteria were enrolled in T2T programme led by Advanced Nurse Practitioner (ANP) with consultant supervision. To assess their response to treatment, we used the Clinical Disease Activity Index (CDAI) . SPSS was used to analyse the data. Results: A total of 353 have completed the programme and of these, 341were commenced on MTX. 208 patients (61%) were female. The MTX starting dose was 15mg for 88.4% (305/341) of patients. The median time to first increment in MTX dose was 7 weeks and the figure 1 was identical for the second increment. Of the 238 patients who started oral MTX, 18.48% (44) discontinued. 21.4% (22) of the 103 who started on SC-MTX discontinued (The p-value for discontinuation was 0.538). P-value for likelihood of achieving remission based on oral versus SC MTX was 0.248 and the p-value for time to achieve remission was 0.671 for oral versus SC MTX groups, see figure 1 attached. Conclusion: Patients in this cohort are being started promptly on an appropriate dose of MTX and are escalated in a timely manner in-line with guidelines. Analysis showed no statistically significant difference in terms of time to remission, likelihood of achieving remission or discontinuation of MTX between oral and SC-MTX groups. References: [1]Carmona L, Villaverde V, Hernández-García C, Ballina J, Gabriel R, Laffon A, et al. The prevalence of rheumatoid arthritis in the general population of Spain. Rheumatology. 2002;41(1):88-95. [2]Rachapalli SM, Williams R, Walsh DA, Young A, Kiely PDW, Choy EH, et al. First-line DMARD choice in early rheumatoid arthritis—do prognostic factors play a role? Rheumatology. 2010;49(7):1267-71. Disclosure of Interests: None declared
Potential Therapeutic Targets for Cisplatin-Induced Kidney Injury: Lessons from Other Models of AKI and Fibrosis
Authors: Sophia M. Sears, Leah J. Siskind
Journal: Journal of the American Society of Nephrology (2021)

The effectiveness of cisplatin, a mainstay in the treatment of many solid organ cancers, is hindered by dose-limiting nephrotoxicity. Cisplatin causes AKI in 30% of patients. Patients who do not develop AKI by clinical standards during treatment are still at risk for long-term decline in kidney function and the development of CKD. The connection between AKI and CKD has become increasingly studied, with renal fibrosis a hallmark of CKD development. To prevent both the short- and long-term effects of cisplatin, researchers must use models that reflect both types of pathology. Although a lot is known about cisplatin-induced AKI, very little is known about the mechanisms by which repeated low levels of cisplatin lead to fibrosis development. In this review, strategies used in various rodent models to prevent kidney injury, its progression to fibrosis, or both, are examined to gain mechanistic insights and identify potential therapeutic targets for cisplatin-induced kidney pathologies. Reviewing the results from these models highlights the diverse and highly complex role of cell death, cell senescence, endoplasmic reticulum stress, autophagy, and immune cell activation in acute and chronic kidney injuries. The use of several models of kidney injury is needed for development of agents that will prevent all aspects of cisplatin-induced kidney injury.
Upregulation of FGF9 in Lung Adenocarcinoma Transdifferentiation to Small Cell Lung Cancer
Authors: Kota Ishioka, Hiroyuki Yasuda, Junko Hamamoto, Hideki Terai, Katsura Emoto, Tae-Jung Kim, Shigemichi Hirose, Takashi Kamatani, Sachiyo Mimaki, Daisuke Arai, Keiko Ohgino, Tetsuo Tani, Keita Masuzawa, Tadashi Manabe, Taro Shinozaki, Akifumi Mitsuishi, Toshiki Ebisudani, Takahiro Fukushima, Mari Ozaki, Shinnosuke Ikemura, Ichiro Kawada, Katsuhiko Naoki, Morio Nakamura, Takashi Ohtsuka, Hisao Asamura, Katsuya Tsuchihara, Yuichiro Hayashi, Ahmed E. Hegab, Susumu S. Kobayashi, Takashi Kohno, Hideo Watanabe, David M. Ornitz, Tomoko Betsuyaku, Kenzo Soejima, Koichi Fukunaga
Journal: Cancer Research (2021)

Abstract Transdifferentiation of lung adenocarcinoma to small cell lung cancer (SCLC) has been reported in a subset of lung cancer cases that bear EGFR mutations. Several studies have reported the prerequisite role of TP53 and RB1 alterations in transdifferentiation. However, the mechanism underlying transdifferentiation remains understudied, and definitive additional events, the third hit, for transdifferentiation have not yet been identified. In addition, no prospective experiments provide direct evidence for transdifferentiation. In this study, we show that FGF9 upregulation plays an essential role in transdifferentiation. An integrative omics analysis of paired tumor samples from a patient with transdifferentiated SCLC exhibited robust upregulation of FGF9. Furthermore, FGF9 upregulation was confirmed at the protein level in four of six (66.7%) paired samples. FGF9 induction transformed mouse lung adenocarcinoma-derived cells to SCLC-like tumors in vivo through cell autonomous activation of the FGFR pathway. In vivo treatment of transdifferentiated SCLC-like tumors with the pan-FGFR inhibitor AZD4547 inhibited growth. In addition, FGF9 induced neuroendocrine differentiation, a pathologic characteristic of SCLC, in established human lung adenocarcinoma cells. Thus, the findings provide direct evidence for FGF9-mediated SCLC transdifferentiation and propose the FGF9–FGFR axis as a therapeutic target for transdifferentiated SCLC. Significance: This study demonstrates that FGF9 plays a role in the transdifferentiation of lung adenocarcinoma to small cell lung cancer.
Fullerol-hydrogel microfluidic spheres for in situ redox regulation of stem cell fate and refractory bone healing
Authors: Jielai Yang, Jing Liang, Yuan Zhu, Mu Hu, Lianfu Deng, Wenguo Cui, Xiangyang Xu
Journal: Bioactive Materials (2021)

The balance of redox homeostasis is key to stem cell maintenance and differentiation. However, this balance is disrupted by the overproduced reactive oxygen species (ROS) in pathological conditions, which seriously impair the therapeutic efficacy of stem cells. In the present study, highly dispersed fullerol nanocrystals with enhanced bioreactivity were incorporated into hydrogel microspheres using one-step innovative microfluidic technology to construct fullerol-hydrogel microfluidic spheres (FMSs) for in situ regulating the redox homeostasis of stem cells and promoting refractory bone healing. It was demonstrated that FMSs exhibited excellent antioxidant activity to quench both intracellular and extracellular ROS, sparing stem cells from oxidative stress damage. Furthermore, these could effectively promote the osteogenic differentiation of stem cells with the activation of FoxO1 signaling, indicating the intrinsically osteogenic property of FMSs. By injecting the stem cells-laden FMSs into rat calvarial defects, the formation of new bone was remarkably reinforced, which is a positive synergic effect from modulating the ROS microenvironment and enhancing the osteogenesis of stem cells. Collectively, the antioxidative FMSs, as injectable stem cell carriers, hold enormous promise for refractory bone healing, which can also be expanded to deliver a variety of other cells, targeting diseases that require in situ redox regulation.
Tackling the Misconception That Cystic Fibrosis Is a “White People’s Disease”
Authors: Rita Rubin
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Revealing ARID1A Function in Gastric Cancer from the Bottom Up
Authors: Maria Paz Zafra, Lukas E. Dow
Journal: Cancer Discovery (2021)

Abstract Summary: In this issue of Cancer Discovery, Lo and colleagues use CRISPR-based genome engineering in primary human gastric organoids to reveal the functional consequences of ARID1A loss in the early stages of gastric cancer. They show that ARID1A disruption is not tolerated in wild-type organoids, but in the context of TP53 loss, leads to WNT suppression, mucinous metaplasia, enhanced tumorigenicity, and selectively toxicity to BIRC5/Survivin inhibition. See related article by Lo et al., p. 1562.
Patient-specific COVID-19 resource utilization prediction using fusion AI model
Authors: Amara Tariq, Leo Anthony Celi, Janice M. Newsome, Saptarshi Purkayastha, Neal Kumar Bhatia, Hari Trivedi, Judy Wawira Gichoya, Imon Banerjee
Journal: npj Digital Medicine (2021)

Abstract The strain on healthcare resources brought forth by the recent COVID-19 pandemic has highlighted the need for efficient resource planning and allocation through the prediction of future consumption. Machine learning can predict resource utilization such as the need for hospitalization based on past medical data stored in electronic medical records (EMR). We conducted this study on 3194 patients (46% male with mean age 56.7 (±16.8), 56% African American, 7% Hispanic) flagged as COVID-19 positive cases in 12 centers under Emory Healthcare network from February 2020 to September 2020, to assess whether a COVID-19 positive patient’s need for hospitalization can be predicted at the time of RT-PCR test using the EMR data prior to the test. Five main modalities of EMR, i.e., demographics, medication, past medical procedures, comorbidities, and laboratory results, were used as features for predictive modeling, both individually and fused together using late, middle, and early fusion. Models were evaluated in terms of precision, recall, F1-score (within 95% confidence interval). The early fusion model is the most effective predictor with 84% overall F1-score [CI 82.1–86.1]. The predictive performance of the model drops by 6 % when using recent clinical data while omitting the long-term medical history. Feature importance analysis indicates that history of cardiovascular disease, emergency room visits in the past year prior to testing, and demographic factors are predictive of the disease trajectory. We conclude that fusion modeling using medical history and current treatment data can forecast the need for hospitalization for patients infected with COVID-19 at the time of the RT-PCR test.
Citrullinated Fibrinogen Renders Clots Mechanically Less Stable, but Lysis-Resistant
Authors: Imre Varjú, Nicoletta Sorvillo, Deya Cherpokova, Ádám Z. Farkas, Veronika J. Farkas, Erzsébet Komorowicz, Tímea Feller, Balázs Kiss, Miklós Z. Kellermayer, László Szabó, András Wacha, Attila Bóta, Colin Longstaff, Denisa D. Wagner, Krasimir Kolev
Journal: Circulation Research (2021)
ミャンマーにおける普遍的な健康範囲に向けての進歩:国家的および国家的評価【JST・京大機械翻訳】
Authors: Han Su Myat, Rahman Md Mizanur, Rahman Md Shafiur, Swe Khin Thet, Palmer Matthew, Sakamoto Haruka, Nomura Shuhei, Shibuya Kenji
Journal: The Lancet Global Health (2018)
Vascular histopathology and connective tissue ultrastructure in spontaneous coronary artery dissection: pathophysiological and clinical implications
Authors: Marios Margaritis, Francesca Saini, Ania A Baranowska-Clarke, Sarah Parsons, Aryan Vink, Charley Budgeon, Natalie Allcock, Bart E Wagner, Nilesh J Samani, Jan von der Thüsen, Jan Lukas Robertus, Mary N Sheppard, David Adlam
Journal: Cardiovascular Research (2021)

Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndromes and in rare cases sudden cardiac death (SCD). Connective tissue abnormalities, coronary inflammation, increased coronary vasa vasorum (VV) density, and coronary fibromuscular dysplasia have all been implicated in the pathophysiology of SCAD but have not previously been systematically assessed. We designed a study to investigate the coronary histological and dermal collagen ultrastructural findings in SCAD.Thirty-six autopsy SCAD cases were compared with 359 SCAD survivors. Coronary and myocardial histology and immunohistochemistry were undertaken. Transmission electron microscopy (TEM) of dermal extracellular matrix (ECM) components of n = 31 SCAD survivors and n = 16 healthy volunteers were compared. Autopsy cases were more likely male (19% vs. 5%; P = 0.0004) with greater proximal left coronary involvement (56% vs. 18%; P < 0.0001) compared to SCAD survivors. N = 24 (66%) of cases showed no myocardial infarction on macro- or microscopic examination consistent with arrhythmogenic death. There was significantly (P < 0.001) higher inflammation in cases with delayed-onset death vs. sudden death and significantly more inflammation surrounding the dissected vs. non-dissected vessel segments. N = 17 (47%) cases showed limited intimal fibro-elastic thickening but no features of fibromuscular dysplasia and no endothelial or internal elastic lamina abnormalities. There were no differences in VV density between SCAD and control cases. TEM revealed no general ultrastructural differences in ECM components or markers of fibroblast metabolic activity.Assessment of SCD requires careful exclusion of SCAD, particularly in cases without myocardial necrosis. Peri-coronary inflammation in SCAD is distinct from vasculitides and likely a reaction to, rather than a cause for SCAD. Coronary fibromuscular dysplasia or increased VV density does not appear pathophysiologically important. Dermal connective tissue changes are not common in SCAD survivors.
AB0738 JUVENILE IDIOPATHIC ARTHRITIS AND SCHOOLING
Authors: H. Tantaoui, K. Nassar, S. Janani
Journal: Annals of the Rheumatic Diseases (2021)

Background: Juvenile idiopathic arthritis (JIA) refers to all chronic inflammatory rheumatism in children without a recognized cause, onset before the age of 16. JIA is associated with significant short- and long-term disability, which influences the education and socio-professional integration of patients who suffers from it. Objectives: Evaluate the impact of JIA on the education and professional integration of affected patients. Methods: This is a retrospective, descriptive and cross-sectional study carried out in the rheumatology department. We included all patient followed in our JIA training. The following information was collected from a questionnaire survey: Educational attainment, main problems experienced during studies, cause of dropping school, and professional data. Results: Forty-two patients were included. The average age was 27.15 years old [18 - 61 years old]. Sex-Ratio (M / F) was 0.9. The forms of JIA were dominated by spondyloarthropathy (48.64%) and the seropositive polyarticular form (18.91%). The mean age of onset of JIA was 10.8 years [6 months - 16 years]. The mean duration of JIA progression was 14.4 years [4 - 27 years]. Regarding education, 2.94% were illiterate, 23.52% had a primary level, 55.87% a secondary level and 17.64% a higher level. The majority of patients (85%) experienced several problems during their studies: joint pain and stiffness (73.52%), absenteeism (50%), limitation in activities (26.47%), problem with adaptation and social integration (11.76%) and fatigue (5.88%). Only 2.94% of patients benefited from an individualized reception protocol apart from a sports exemption which represents 38.23%. 73.52% of patients received encouragement to continue their studies by those around them (parents, teachers and attending physicians). Discontinuation of schooling was observed in 70.58% of patients with 8.82% of patients dropping school before the onset of JIA and 61.76% of patients related to JIA. School studies were still ongoing in 23.52% of patients. Regarding the professional side, unemployment affects 52.94% of these patients and workers represent 23.52%. Conclusion: In our series, the level of education of JIA patients does not exceed secondary level in 80% of cases. The implementation of an individualized reception protocol is strongly recommended to facilitate the education of these patients and to fight against the main problems experienced. The professional integration of patients with JIA should also be adopted. Disclosure of Interests: None declared
High antibody response to two-dose SARS-CoV-2 messenger RNA vaccination in patients with rheumatic and musculoskeletal diseases
Authors: Jake A Ruddy, Caoilfhionn Marie Connolly, Brian J Boyarsky, William A Werbel, Lisa Christopher-Stine, Jacqueline Garonzik-Wang, Dorry L Segev, Julie J Paik
Journal: Annals of the Rheumatic Diseases (2021)

<h3>Abstract</h3> <h3>Background</h3> State health departments have been responsible for prioritizing and allocating SARS-CoV-2 tests and vaccines. Testing and vaccination recommendations in the United States varied by state and over time, as did vaccine rollouts, COVID-19 cases, and estimates of excess mortality. <h3>Methods</h3> We compiled data about COVID-19 testing, cases, and deaths, and excess pneumonia + influenza + COVID-19 deaths to assess relationships between testing recommendations, <i>per capita</i> tests performed, epidemic intensity, and excess mortality during the early months of the COVID-19 pandemic in the United States. We compiled further data about state-level SARS-CoV-2 vaccination policies and doses administered during the early months of the vaccine rollout. <h3>Results</h3> As of July 2020, 16 states recommended testing asymptomatic members of the general public. The rate of COVID-19 tests reported in each state correlated with more inclusive testing recommendations and with higher epidemic intensity. Higher <i>per capita</i> testing was associated with more complete reporting of COVID-19 deaths, which is a fundamental requirement for analyzing the pandemic. Testing <i>per capita</i> during the first three months was associated with vaccination <i>per capita</i> in the first three months of rollout. <i>Per capita</i> vaccine doses in each state were not associated with adherence to national guidelines. <h3>Conclusions</h3> Reported deaths due to COVID-19 likely represent an undercount of the true burden of the pandemic. States that struggled with testing rollout have also frequently struggled with vaccine rollout. Coordinated, consistent guidelines for COVID-19 testing and vaccine administration should be a high priority for state and national health systems.
Helen Salisbury: Mind the training gap
Authors: Helen Salisbury
Journal: BMJ (2021)

Learning to be a good doctor is a complicated business, one that doesn’t end until the day we retire. As well as understanding how bodies work and go wrong, and what can be done to put them right, we also need to learn many practical skills—how to listen so that patients feel heard, how to examine an abdomen or stitch a wound. While some of this knowledge is found in books or delivered in formal teaching sessions, a huge amount of medical training remains an apprenticeship where we learn from others who already know how to do it. The problem …
Deciphering Discordance between MYC mRNA and MYC IHC in DLBCL: The Role of MYC Exon 2 Mutations and N11S Polymorphism
Authors: Brett Collinge, Lauren Chong, Susana Ben-Neriah, Graham W Slack, Daisuke Ennishi, Anja Mottok, Pedro Farinha, Merrill Boyle, Barbara Meissner, Alina S Gerrie, Diego Villa, Kerry J Savage, Laurie H. Sehn, Ryan D. Morin, Andrew J. Mungall, Randy D. Gascoyne, Marco A. Marra, Joseph M Connors, Christian Steidl, David W. Scott
Journal: Blood (2017)
Abstract 17808: Long Term Prognoses of Patients With and Without Left Anterior Descending Coronary Artery Stenosis in the DES Era
Authors: Kensuke Shimazaki, Kentaro Jujo, Yuichiro Minami, Shintaro Haruki, Ryosuke Itani, Hisao Otsuki, Masaru Nakao, Junichi Yamaguchi, Hiroshi Ogawa, Nobuhisa Hagiwara
Journal: Circulation (2016)

Background: Atherosclerosis in patients with coronary artery disease (CAD) generally starts at the proximal sit of left anterior descending (LAD) artery. However, CAD without LAD was frequently ide...
Airway mucin MUC5AC and MUC5B concentrations and the initiation and progression of chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort
Authors: Giorgia Radicioni, Agathe Ceppe, Amina A Ford, Neil E Alexis, R Graham Barr, Eugene R Bleecker, Stephanie A Christenson, Christopher B Cooper, MeiLan K Han, Nadia N Hansel, Annette T Hastie, Eric A Hoffman, Richard E Kanner, Fernando J Martinez, Esin Ozkan, Robert Paine, Prescott G Woodruff, Wanda K O'Neal, Richard C Boucher, Mehmet Kesimer
Journal: The Lancet Respiratory Medicine (2021)
pH‐Sensitive, Cerebral Vasculature‐Targeting Hydroxyethyl Starch Functionalized Nanoparticles for Improved Angiogenesis and Neurological Function Recovery in Ischemic Stroke
Authors: Hang Yang, Yan Luo, Hang Hu, Sibo Yang, Yanan Li, Huijuan Jin, Shengcai Chen, Quanwei He, Candong Hong, Jiehong Wu, Yan Wan, Man Li, Zifu Li, Xiangliang Yang, Ying Su, Yifan Zhou, Bo Hu
Journal: Advanced Healthcare Materials (2021)

Abstract Angiogenesis, an essential restorative process following ischemia, is a promising therapeutic approach to improve neurological deficits. However, overcoming the blood–brain barrier (BBB) and effective drug enrichment are challenges for conventional drug delivery methods, which has limited the development of treatment strategies. Herein, a dual‐targeted therapeutic strategy is reported to enable pH‐sensitive drug release and allow cerebral ischemia targeting to improve stroke therapeutic efficacy. Targeted delivery is achieved by surface conjugation of Pro‐His‐Ser‐Arg‐Asn (PHSRN) peptides, which binds to integrin α 5 β 1 enriched in the cerebral vasculature of ischemic tissue. Subsequently, smoothened agonist (SAG), an activator of sonic hedgehog (Shh) signaling, is coupled to PHSRN‐HES by pH‐dependent electrostatic adsorption. SAG@PHSRN‐HES nanoparticles can sensitively release more SAG in the acidic environment of ischemic brain tissue. More importantly, SAG@PHSRN‐HES exerts the synergistic mechanisms of PHSRN and SAG to promote angiogenesis and BBB integrity, thus improving neuroplasticity and neurological function recovery. This study proposes a new approach to improve the delivery of medications in the ischemic brain. Dual‐targeted therapeutic strategies have excellent potential to treat patients suffering from cerebral infarction.