tbuckley/cabot-search huggingface dataset:
SARS-CoV-2 infection among inpatients with systemic lupus erythematosus in France: a nationwide epidemiological study
Authors: Arthur Mageau, Geoffrey Aldebert, Damien Van Gysel, Thomas Papo, Jean-François Timsit, Karim Sacre
Journal: Annals of the Rheumatic Diseases (2021)

Since the global emergence of SARS-CoV-2 at the end of 2019, a special concern has raised regarding patients with rheumatic and inflammatory diseases, such as systemic lupus erythematosus (SLE).1 Indeed, many treated patients with SLE are immunocompromised and often suffer from chronic kidney or cardiovascular diseases.2 Recently, anti-interferon antibodies have been implicated in severe SARS-CoV-2 infection3 while it has been known for decades that patients with SLE may produce such autoantibodies.4 Although available data from short SLE series are reassuring,5 6 large-scale nationwide studies are still needed to assess the risk of developing severe SARS-CoV-2 infection in SLE.

We therefore used the French healthcare database system called ‘Programme de Medicalisation des Systemes d’Information’—which contains hospitalisation data of all inpatients in France—to analyse the population with SLE that had at least one stay in a French hospital between March and 30 October 2020 (online supplemental material). On this population, we compared inpatients with SLE with or without SARS-CoV-2 infection (SLE/COVID-19+, SLE/COVID-19−). Among SLE/COVID-19+ inpatients, we distinguished patients with poor outcome after SARS-CoV-2 infection and …
Faciogenital Dysplasia 5 supports cancer stem cell traits in basal-like breast cancer by enhancing EGFR stability
Authors: Ke Li, Ting-ting Zhang, Chen-xi Zhao, Feng Wang, Bing Cui, Zhao-na Yang, Xiao-xi Lv, Zaiwuli Yeerjiang, Yu-fen Yuan, Jin-mei Yu, Zhen-he Wang, Xiao-wei Zhang, Jiao-jiao Yu, Shan-shan Liu, Shuang Shang, Bo Huang, Fang Hua, Zhuo-wei Hu
Journal: Science Translational Medicine (2021)

Most basal-like breast cancers (BLBCs) are triple-negative breast cancers (TNBCs), which have the worst prognosis and distant metastasis-free survival among breast cancer subtypes. Now, no targeted therapies are available for patients with BLBC due to the lack of reliable and effective molecular targets. Here, we performed the BLBC tissue microarray-based immunohistochemical analysis and showed that Faciogenital Dysplasia 5 (FGD5) abundance is associated with poor prognosis in BLBCs. FGD5 deletion decreased the proliferation, invasion, and tumorsphere formation capacity of BLBC cells. Furthermore, genetic inhibition of Fgd5 in mouse mammary epithelial cells attenuated BLBC initiation and progression by reducing the self-renewal ability of tumor-initiating cells. In addition, FGD5 abundance was positively correlated with the abundance of epidermal growth factor receptor (EGFR) in BLBCs. FGD5 ablation decreased EGFR abundance by reducing EGFR stability in TNBC cells in 2D and 3D culture conditions. Mechanistically, FGD5 binds to EGFR and interferes with basal EGFR ubiquitination and degradation induced by the E3 ligase ITCH. Impaired EGFR degradation caused BLBC cell proliferation and promoted invasive properties and self-renewal. To verify the role of the FGD5-EGFR interaction in the regulation of EGFR stability, we screened a cell-penetrating α-helical peptide PER3 binding with FGD5 to disrupt the interaction. Treatment of BLBC patient-derived xenograft-bearing mice with the peptide PER3 disrupting the FGD5-EGFR interaction either with or without chemotherapy reduced BLBC progression. Our study identified FGD5 as a positive modulator of tumor-initiating cells and suggests a potential therapeutic option for the BLBC subtype of breast cancer.
Abstract 16067: Unique Challenge of Acs - Anomalous Left Main Coronary Artery From Right Coronary Cusp
Authors: Srinivas Nadadur, Justice Oranefo, Muhammad Adeel, Mansour Khaddr, Wassim Mosleh
Journal: Circulation (2020)

Introduction: Anomalous aortic origin of coronary arteries (AAOCA) is uncommon congenital anomalies of the coronary circulation. Anomalous left main coronary artery (LMCA) originating from the right cusp is one of the rarer anomalies (incidence ~ 0.03% of patients undergoing coronary angiography). Mostly asymptomatic, however, this may become clinically significant with symptoms ranging from atypical chest discomfort to sudden cardiac death. We present a case of anomalous origin LMCA from the right coronary cusp. Case presentation: A 47-year-old female presented to the ED with three days of substernal chest pressure at rest. BP 106/71 mmHg, pulse 72 bpm, normal regular heart sounds, and clear lungs. The ECG showed new anterolateral T-wave inversions. Troponin-I was 0.31 ng/ mL. Echocardiogram showed normal LVEF without focal wall motion abnormalities. Coronary angiography revealed a dominant patent RCA without any disease. LMCA originated from the right coronary cusp with focal 90% ostial LAD stenosis. The rest of the coronary tree was free of disease. CABG with LIMA to LAD and SVG to OM1 was performed. Discussion: AAOCA presents a unique challenge to diagnosis and management. CT coronary angiogram or magnetic resonance angiography is recommended for more accurate delineation of the course of the coronary vessel. The diagnostic challenge to effectively engage the anomalous artery and to obtain coronary angiogram to delineate anatomy is critical in further management. As seen in our case, this is easy to overlook and in the acute event could lead to unnecessary delay.
PS01.09 Pembrolizumab Plus Ipilimumab vs Pembrolizumab Plus Placebo as 1L Therapy for Metastatic NSCLC of PD-L1 TPS ≥50%: KEYNOTE-598
Authors: M. Boyer, M.A.N. Sendur, D. Rodríguez-Abreu, K. Park, D.H. Lee, I. Cicin, P.F. Yumuk, F. Orlandi, T. Leal, O. Molinier, N. Soparattanapaisam, A. Langleben, R. Califano, B. Medgyasszay, T. Hsia, G. Otterson, L. Xu, B. Piperdi, A. Samkari, M. Reck
Journal: Journal of Thoracic Oncology (2021)
Current approaches to management of high‐risk multiple myeloma
Authors: Sarah Goldman‐Mazur, Shaji K. Kumar
Journal: American Journal of Hematology (2021)

The median overall survival in multiple myeloma is rapidly approaching 10 years; however, in nearly a fifth of patients the prognosis remains poor. Therefore, the modern-day management of myeloma patients should be individualized, with a more intense and continuous approach in these high-risk patients. This includes first-line treatment based on multi-drug combinations employing the most effective drug combinations, upfront autologous stem cell transplantation (in eligible patients with tandem transplantation being a consideration), and maintenance based on proteasome inhibitor-based combinations. This paper reviews the results of recent retrospective analyses and clinical trials, but also gives a glance into the future by presenting the ongoing trials.
Signal-Transducing Adaptor Protein-2 Blocks B Cell Recovery Under Hematological Stress at Pre-B Stage Via TLR4 Signaling
Authors: Michiko Ichii, Kenji Oritani, Hirohiko Shibayama, Jun Toda, Hideaki Saito, Yuichi Kitai, Ryuta Muromoto, Jun-ichi Kashiwakura, Kodai Saitoh, Tadashi Matsuda, Yuzuru Kanakura
Journal: Blood (2017)
Neuroanatomical Substrates and Symptoms Associated With Magnetic Resonance Imaging of Patients With Mild Traumatic Brain Injury
Authors: Sophie Richter, Stefan Winzeck, Evgenios N. Kornaropoulos, Tilak Das, Thijs Vande Vyvere, Jan Verheyden, Guy B. Williams, Marta M. Correia, David K. Menon, Virginia F. J. Newcombe
Journal: JAMA Network Open (2021)

Persistent symptoms after mild traumatic brain injury (mTBI) represent a major public health problem.To identify neuroanatomical substrates of mTBI and the optimal timing for magnetic resonance imaging (MRI).This prospective multicenter cohort study encompassed all eligible patients from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study (December 19, 2014, to December 17, 2017) and a local cohort (November 20, 2012, to December 19, 2013). Patients presented to the hospital within 24 hours of an mTBI (Glasgow Coma Score, 13-15), satisfied local criteria for computed tomographic scanning, and underwent MRI scanning less than 72 hours (MR1) and 2 to 3 weeks (MR2) after injury. In addition, 104 control participants were enrolled across all sites. Data were analyzed from January 1, 2019, to December 31, 2020.Mild TBI.Volumes and diffusion parameters were extracted via automated bespoke pipelines. Symptoms were measured using the Rivermead Post Concussion Symptoms Questionnaire in the short term and the extended Glasgow Outcome Scale at 3 months.Among the 81 patients included in the analysis (73 CENTER-TBI and 8 local), the median age was 45 (interquartile range [IQR], 24-59; range, 14-85) years, and 57 (70.4%) were male. Structural sequences were available for all scans; diffusion data, for 73 MR1 and 79 MR2 scans. After adjustment for multiple comparisons between scans, visible lesions did not differ significantly, but cerebral white matter volume decreased (MR2:MR1 ratio, 0.98; 95% CI, 0.96-0.99) and ventricular volume increased (MR2:MR1 ratio, 1.06; 95% CI, 1.02-1.10). White matter volume was within reference limits on MR1 scans (patient to control ratio, 0.99; 95% CI, 0.97-1.01) and reduced on MR2 scans (patient to control ratio, 0.97; 95% CI, 0.95-0.99). Diffusion parameters changed significantly between scans in 13 tracts, following 1 of 3 trajectories. Symptoms measured by Rivermead Post Concussion Symptoms Questionnaire scores worsened in the progressive injury phenotype (median, +5.00; IQR, +2.00 to +5.00]), improved in the minimal change phenotype (median, -4.50; IQR, -9.25 to +1.75), and were variable in the pseudonormalization phenotype (median, 0.00; IQR, -6.25 to +9.00) (P = .02). Recovery was favorable for 33 of 65 patients (51%) and was more closely associated with MR1 than MR2 (area under the curve, 0.87 [95% CI, 0.78-0.96] vs 0.75 [95% CI, 0.62-0.87]; P = .009).These findings suggest that advanced MRI reveals potential neuroanatomical substrates of mTBI in white matter and is most strongly associated with odds of recovery if performed within 72 hours, although future validation is required.
P83.02 Niraparib + Pembrolizumab (Pembro) Versus Placebo + Pembro 1L Maintenance Therapy in Advanced NSCLC: ZEAL-1L Phase III Study
Authors: S. Ramalingam, S. Arora, M. Whipple Neibauer, J. Zhou, S. Hazard, T. Frenkl, A. Stojadinovic, S. Peters
Journal: Journal of Thoracic Oncology (2021)
Cell-permeable transgelin-2 as a potent therapeutic for dendritic cell-based cancer immunotherapy
Authors: Hye-Ran Kim, Jeong-Su Park, Jin-Hwa Park, Fatima Yasmin, Chang-Hyun Kim, Se Kyu Oh, Ik-Joo Chung, Chang-Duk Jun
Journal: Journal of Hematology & Oncology (2021)

Abstract Background Transgelin-2 is a 22 kDa actin-binding protein that has been proposed to act as an oncogenic factor, capable of contributing to tumorigenesis in a wide range of human malignancies. However, little is known whether this tiny protein also plays an important role in immunity, thereby keeping body from the cancer development and metastasis. Here, we investigated the functions of transgelin-2 in dendritic cell (DC) immunity. Further, we investigated whether the non-viral transduction of cell-permeable transgelin-2 peptide potentially enhance DC-based cancer immunotherapy. Methods To understand the functions of transgelin-2 in DCs, we utilized bone marrow-derived DCs (BMDCs) purified from transgelin-2 knockout ( Tagln2 −/− ) mice. To observe the dynamic cellular mechanism of transgelin-2, we utilized confocal microscopy and flow cytometry. To monitor DC migration and cognate T–DC interaction in vivo, we used intravital two-photon microscopy. For the solid and metastasis tumor models, OVA + B16F10 melanoma were inoculated into the C57BL/6 mice via intravenously (i.v.) and subcutaneously (s.c.), respectively. OTI TCR T cells were used for the adoptive transfer experiments. Cell-permeable, de-ubiquitinated recombinant transgelin-2 was purified from Escherichia coli and applied for DC-based adoptive immunotherapy. Results We found that transgelin-2 is remarkably expressed in BMDCs during maturation and lipopolysaccharide activation, suggesting that this protein plays a role in DC-based immunity. Although Tagln2 −/− BMDCs exhibited no changes in maturation, they showed significant defects in their abilities to home to draining lymph nodes (LNs) and prime T cells to produce antigen-specific T cell clones, and these changes were associated with a failure to suppress tumor growth and metastasis of OVA + B16F10 melanoma cells in mice. Tagln2 −/− BMDCs had defects in filopodia-like membrane protrusion and podosome formation due to the attenuation of the signals that modulate actin remodeling in vitro and formed short, unstable contacts with cognate CD4 + T cells in vivo. Strikingly, non-viral transduction of cell-permeable, de-ubiquitinated recombinant transgelin-2 potentiated DC functions to suppress tumor growth and metastasis. Conclusion This work demonstrates that transgelin-2 is an essential protein for both cancer and immunity. Therefore, transgelin-2 can act as a double-edged sword depending on how we apply this protein to cancer therapy. Engineering and clinical application of this protein may unveil a new era in DC-based cancer immunotherapy. Our findings indicate that cell-permeable transgelin-2 have a potential clinical value as a cancer immunotherapy based on DCs.
Development and external validation of the Psychosis Metabolic Risk Calculator (PsyMetRiC): a cardiometabolic risk prediction algorithm for young people with psychosis
Authors: Benjamin I Perry, Emanuele F Osimo, Rachel Upthegrove, Pavan K Mallikarjun, Jessica Yorke, Jan Stochl, Jesus Perez, Stan Zammit, Oliver Howes, Peter B Jones, Golam M Khandaker
Journal: The Lancet Psychiatry (2021)

BackgroundYoung people with psychosis are at high risk of developing cardiometabolic disorders; however, there is no suitable cardiometabolic risk prediction algorithm for this group. We aimed to develop and externally validate a cardiometabolic risk prediction algorithm for young people with psychosis.MethodsWe developed the Psychosis Metabolic Risk Calculator (PsyMetRiC) to predict up to 6-year risk of incident metabolic syndrome in young people (aged 16–35 years) with psychosis from commonly recorded information at baseline. We developed two PsyMetRiC versions using the forced entry method: a full model (including age, sex, ethnicity, body-mass index, smoking status, prescription of a metabolically active antipsychotic medication, HDL concentration, and triglyceride concentration) and a partial model excluding biochemical results. PsyMetRiC was developed using data from two UK psychosis early intervention services (Jan 1, 2013, to Nov 4, 2020) and externally validated in another UK early intervention service (Jan 1, 2012, to June 3, 2020). A sensitivity analysis was done in UK birth cohort participants (aged 18 years) who were at risk of developing psychosis. Algorithm performance was assessed primarily via discrimination (C statistic) and calibration (calibration plots). We did a decision curve analysis and produced an online data-visualisation app.Findings651 patients were included in the development samples, 510 in the validation sample, and 505 in the sensitivity analysis sample. PsyMetRiC performed well at internal (full model: C 0·80, 95% CI 0·74–0·86; partial model: 0·79, 0·73–0·84) and external validation (full model: 0·75, 0·69–0·80; and partial model: 0·74, 0·67–0·79). Calibration of the full model was good, but there was evidence of slight miscalibration of the partial model. At a cutoff score of 0·18, in the full model PsyMetRiC improved net benefit by 7·95% (sensitivity 75%, 95% CI 66–82; specificity 74%, 71–78), equivalent to detecting an additional 47% of metabolic syndrome cases.InterpretationWe have developed an age-appropriate algorithm to predict the risk of incident metabolic syndrome, a precursor of cardiometabolic morbidity and mortality, in young people with psychosis. PsyMetRiC has the potential to become a valuable resource for early intervention service clinicians and could enable personalised, informed health-care decisions regarding choice of antipsychotic medication and lifestyle interventions.FundingNational Institute for Health Research and Wellcome Trust.
Resolving the Gestational Diabetes Diagnosis Conundrum: The Need for a Randomized Controlled Trial of Treatment
Authors: Rudolf W. Bilous, Paul B. Jacklin, Michael J. Maresh, David A. Sacks
Journal: Diabetes Care (2021)

The diagnosis of and criteria for gestational diabetes mellitus (GDM) continue to divide the scientific and medical community, both between and within countries. Many argue for universal adoption of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria and feel that further clinical trials are unjustified and even unethical. However, there are concerns about the large increase in number of women who would be diagnosed with GDM using these criteria and the subsequent impact on health care resources and the individual. This Perspective reviews the origins of the IADPSG consensus and points out some of its less well-known limitations, particularly with respect to identifying women at risk for an adverse pregnancy outcome. It also questions the clinical and cost-effectiveness data often cited to support the IADPSG glycemic thresholds. We present the argument that adoption of diagnostic criteria defining GDM should be based on response to treatment at different diagnostic thresholds of maternal glycemia. This will likely require an international multicenter trial of treatment.
Progression characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS): a 4-year cohort study
Authors: Kathrin Reetz, Imis Dogan, Ralf-Dieter Hilgers, Paola Giunti, Michael H Parkinson, Caterina Mariotti, Lorenzo Nanetti, Alexandra Durr, Claire Ewenczyk, Sylvia Boesch, Wolfgang Nachbauer, Thomas Klopstock, Claudia Stendel, Francisco Javier Rodríguez de Rivera Garrido, Christian Rummey, Ludger Schöls, Stefanie N Hayer, Thomas Klockgether, Ilaria Giordano, Claire Didszun, Myriam Rai, Massimo Pandolfo, Jörg B Schulz, Robyn Labrum, Gilbert Thomas-Black, Katarina Manso, Nita Solanky, Cinzia Gellera, Alessia Mongelli, Anna Castaldo, Mario Fichera, Francesc Palau, Mar O'Callaghan, Marie Biet, Marie Lorraine Monin, Andreas Eigentler, Elisabetta Indelicato, Matthias Amprosi, Florentine Radelfahr, Almut T. Bischoff, Florian Holtbernd, Nikolina Brcina, Christian Hohenfeld, Georgios Koutsis, Marianthi Breza, Enrico Bertini, Gessica Vasco
Journal: The Lancet Neurology (2021)
Cancer cell survival in an anaerobic environment with and without elevated carbon dioxide concentrations
Authors: Nicholas Skeen, Jermey Hsu, James Hutson, Herbert Janssen
Journal: Cancer Research (2007)

1377  The delivery of drugs to solid tumor has long been a difficult problem for both the clinician and researcher. Limited blood flow to the interior of the tumor coupled with elevated interstitial pressure has provided a formidable barrier. Although proven effective in certain settings, the use of anti-angiogenesis drugs as an anticancer therapy has met with limited success when used as a single agent to treat mature tumors. The current research was undertaken to better understand cell existence in the interior of solid tumors. Previous research has demonstrated that tumor cells survive in the “necrotic” interior of solid tumors induced in immunosuppressed rats by the injection of UMR-106 cancer cells. The lack of blood supply to this region suggests a lack of O2, and increased concentration of CO2, and a decreased pH. Osteogenic sarcoma cells (ATCC-UMR-106) and cells harvested from the center of a mature tumor induced in a immunosuppressed rat (by injection of UMR-106 cells) were grown in culture and exposed to increasing concentrations of CO2. Cell viability continued up to and including CO2 concentrations approaching 100% for five days. This is equal to a media pH of approximately 6.3. These results suggest that tumor cells are able to maintain viability without the presence of O2 and in the presence of extremely high CO2 levels. In a separate study these cells were maintained in a standard anaerobic bacteria chamber for a similar time period. This media has a pH of approximately 7.8. These results suggest that the cancer cells remain viable in an anaerobic environment at a high pH without CO2. Cells in the anaerobic conditions without CO2 appeared to survive better that when anaerobic conditions were produced by replacement if air with CO2. When combined, these results provide evidence that cancer cells are able to survive in an environment without O2 both with and without elevated CO2 or pH for an extended period of time. This may help explain why removal of new blood vessel growth with anti-angiogenesis compounds has not achieved the clinical results initially expected. Supported impart by the Clark Scholar Program at Texas Tech University
Postoperative Chemotherapy Use and Outcomes From ADAURA: Osimertinib as Adjuvant Therapy for Resected EGFR-Mutated NSCLC
Authors: Yi-Long Wu, Thomas John, Christian Grohe, Margarita Majem, Jonathan W. Goldman, Sang-We Kim, Terufumi Kato, Konstantin Laktionov, Huu Vinh Vu, Zhijie Wang, Shun Lu, Kye Young Lee, Charuwan Akewanlop, Chong-Jen Yu, Filippo de Marinis, Laura Bonanno, Manuel Domine, Frances A. Shepherd, Lingmin Zeng, Ajlan Atasoy, Roy S. Herbst, Masahiro Tsuboi
Journal: Journal of Thoracic Oncology (2021)

Adjuvant chemotherapy is recommended in patients with resected stages II to IIIA (and select IB) NSCLC; however, recurrence rates are high. In the phase 3 ADAURA study (NCT02511106), osimertinib was found to have a clinically meaningful improvement in disease-free survival (DFS) in patients with resected stages IB to IIIA EGFR-mutated (EGFRm) NSCLC. Here, we report prespecified and exploratory analyses of adjuvant chemotherapy use and outcomes from ADAURA.Patients with resected stages IB to IIIA EGFRm NSCLC were randomized 1:1 to receive osimertinib or placebo for 3 years. Adjuvant chemotherapy before randomization was not mandatory, per physician and patient choice. DFS in the overall population (IB-IIIA), with and without adjuvant chemotherapy, was a prespecified analysis. Exploratory analyses included the following: adjuvant chemotherapy use by patient age, disease stage, and geographic location; DFS by adjuvant chemotherapy use and disease stage.Overall, 410 of 682 patients (60%) received adjuvant chemotherapy (osimertinib, n = 203; placebo, n = 207) for a median duration of 4.0 cycles. Adjuvant chemotherapy use was more frequent in patients: aged less than 70 years (338 of 509; 66%) versus more than or equal to 70 years (72 of 173; 42%); with stages II to IIIA (352 of 466; 76%) versus stage IB (57 of 216; 26%); and enrolled in Asia (268 of 414; 65%) versus outside of Asia (142 of 268; 53%). A DFS benefit favoring osimertinib versus placebo was observed in patients with (DFS hazard ratio = 0.16, 95% confidence interval: 0.10-0.26) and without adjuvant chemotherapy (hazard ratio = 0.23, 95% confidence interval: 0.13-0.40), regardless of disease stage.These findings support adjuvant osimertinib as an effective treatment for patients with stages IB to IIIA EGFRm NSCLC after resection, with or without previous adjuvant chemotherapy.