tbuckley/cabot-search huggingface dataset:
COVID-19 Outbreak - New York City, February 29-June 1, 2020 (vol 69, pg 1725, 2020)
Authors: C. N. Thompson, J. Baumgartner, C. Pichardo, B. Toro, L. Li, R. Arciuolo, P. Y. Chan, J. Chen, G. Culp, A. Davidson, K. Devinney, A. Dorsinville, M. Eddy, M. English, A. M. Fireteanu, L. Graf, A. Geevarughese, S. K. Greene, K. Guerra, M. Huynh, C. Hwang, M. Iqbal, J. Jessup, J. Knorr, R. Lall, J. Latash, E. Lee, K. Lee, W. H. Li, R. Mathes, E. McGibbon, N. McIntosh, M. Montesano, M. S. Moore, K. Murray, S. Ngai, M. Paladini, R. Paneth-Pollak, H. Parton, E. Peterson, R. Pouchet, J. Ramachandran, K. Reilly, J. S. Slutsker, G. Van Wye, A. Wahnich, A. Winters, M. Layton, L. Jones, V. Reddy, A. Fine
Journal: MMWR Morbidity and Mortality Weekly Report (2020)
Pre-Transplantation Suppression of Haemopoiesis Is Associated with a High Rate of Macrophage Activation Syndrome in Ptcy Haploidentical Transplantation for Haemoglobinopathies
Authors: Satyendra Katewa, Gaurav Kharya, Leena Karnik, Adetola A. Kassim, Josu de la Fuente
Journal: Blood (2017)
Reforming medical education: we must retain innovative training solutions developed in response to covid-19
Authors: Colin Melville
Journal: BMJ (2021)

We agree that new graduates must be prepared for the everyday realities of postgraduate training.1 In recent years, we’ve been thinking differently about the balance between training, assessment,2 and service pressures. The pandemic has accelerated innovative training solutions and we must retain these positive changes.

The foundation interim year 1 intervention to boost our pandemic workforce seems to …
Association of B cells in tumor microenvironment (TME) with clinical benefit to programmed cell death protein-1 (PD-1) blockade therapy in esophageal squamous cell carcinoma (ESCC).
Authors: Jhe-Cyuan Guo, Chia-Lang Hsu, Yen-Lin Huang, Chia-Chi Lin, Ta-Chen Huang, Chun-Jung Chang, Hung-Yang Kuo, Chih-Hung Hsu
Journal: Journal of Clinical Oncology (2021)

237 Background: Previous studies have indicated B cells as potential predictive markers for anti-PD-1 blockade therapy in several cancer types. The study explored whether B cells in TME and B cell related gene signatures are associated with clinical benefit (CB) for ESCC patients receiving anti-PD-1/PD-ligand 1 (PD-L1) therapy. Methods: Sixty-six ESCC patients treated with PD-1/PD-L1 blockade-based immunotherapy were enrolled. Tumor response was evaluated per RECIST 1.1, and CB was defined as complete response, partial response or stable disease at least 6 months. Transcriptome of formalin-fixed paraffin-embedded ESCC tissues were generated by NanoString nCounter platform with Human PanCancer Immune Profiling panel (n=25), Gene Set Enrichment Analysis (GSEA) was performed to identify the differential immune-related pathways, and CIBERSORT was applied to estimate the levels of infiltrating immune cells. The expression of CD20 was evaluated by immunohistochemistry (IHC) (n=66). Results: Of 66 enrolled patients (M: F= 65: 1, median age of 59), 44 and 22 were of recurrent and de novo metastatic ESCC. Forty and 26 received PD-1/PD-L1 blockade alone and PD-1/PD-L1-based combination immunotherapy, respectively. The response rate was 17%, and the CB rate was 24%. The median progression-free-survival (PFS) and overall survival are 1.8 and 5.5 months, respectively. B cell signature was significantly increased in patients with CB ( P &lt; 0.05) and associated with longer progression-free survival and overall survival (both P &lt; 0.05). The genes related to B cells, B cell functions, and T cell functions were up-regulated in patients with CB compared to that with non-CB (all P &lt; 0.05). Naïve B cells and plasma cells were significantly increased in patients with CB (both P &lt; 0.05). The expression levels of stromal CD20 by IHC trended to increase in patients with CB ( P = 0.08). Conclusions: B cells in tumor microenvironment may be associated with CB of anti-PD-1/PD-L1 therapy in patients with ESCC. (Funded by MOST 105-2314-B-002 -186 -MY3; MOHW107-TDU-B-211-114017; MOST 108-2314-B-002 -076 -MY3; MOST 107-2314-B-002-199 -).
FRI0047 Treatment of rheumatoid vasculitis with infliximab
Authors: M Kayser, L Unger, H Nüblein
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Rheumatoid vasculitis (RV) is a systemic late stage complication in patients with rheumatoid arthritis (RA). Despite cyclophosphamide (CYC) therapy which is the treatment of choice the prognosis is very poor and most patients die within two years. From our last ten patients with RV who had to be treated by CYC five patients had to stop therapy because of serious complications like infection orcardiac failure. Three patients refractory to CYC were treated with infliximab. A 48 year old male RA patient developed systemic vasculitis with a pericardial effusion, which did not respond to pulse corticosteroids, CYC or even to plasmapheresis. The only way to manage this life threatening condition was to drain the effusion continuously. Infliximab therapy at 3 mg/kg was initiated. The pericardial effusion as well as all other signs of the systemic vasculitis resolved within two weeks. The second patient, a 62 year old man who underwent abdominal surgery -retrospectively probably because of vasculitis- developed vasculitic skin ulcers on the scrotum, the lower legs and in the abdominal wound. Since CYC and methotrexate only lead to a partial remission, infliximab infusions were given. Again, the vasculitic lesions healed. The last case is a 58 year old woman with a more classic RV characterised by crural ulcers. After getting panmyelopathy caused by CYC, infliximab was given and the vasculitic features disappeared. No complications of infliximab therapy occurred although two patients had superinfected skin ulcers. Our cases show that infliximab is an effective salvage therapy in patients with RV refractory to even CYC. Given the toxicity and complication rate of CYC in this RA patient subset infliximab may well be considered as a first choice alternative to CYC. <h3>Objectives</h3> <h3>Methods</h3> <h3>Results</h3> <h3>Conclusion</h3>
Abstract 12061: Preclinical Efficacy Studies of Human Ips Cell-derived Cardiac Tissue Transplantation Onto Animal Heart Disease Models
Authors: Hidetoshi Masumoto, Shingo Hirao, Shinya Takimoto, Masahide Kawatou, Tadashi Ikeda, Yasuhiko Tabata, Jun Yamashita, Kenji Minatoya
Journal: Circulation (2019)

Introduction: We have been investigating cardiac regenerative medicine using human induced pluripotent stem cells (hiPSCs) with our robust differentiation system toward cardiovascular populations (...
Resection rate of locally advanced pancreatic cancer in gemcitabine plus nab-paclitaxel versus FOLFIRINOX.
Authors: Shahriar Sharif, Amer H. Zureikat, Paula M. Novelli, Charles D. Lopez, Adel Kardosh, Ki Y. Chung, Wesley B. Jones, Hassan Hatoum, Kenneth Lee Meredith, Emmanuel E. Zervos, Antonio Ucar, Ripal T Gandhi, Reza Nazemzadeh, Pashtoon Murtaza Kasi, Erik Vandestraeten, Jochen Decaestecker, Thierry Delaunoit, Charles Charles Li, Ramtin Agah, Michael J. Pishvaian
Journal: Journal of Clinical Oncology (2021)

381 Background: There is no established treatment for locally advanced pancreatic cancer (LAPC), but by utilizing the regimens approved for metastatic pancreatic cancer, hope remains for rendering tumors resectable with chemotherapy. In this context, we looked at the resection rate in patients receiving gemcitabine plus nab-paclitaxel (Gem-Nab) in a prospective trial of patients with LAPC. Methods: TIGeR-PaC is an ongoing phase III clinical trial, studying the role of intra-arterial Gemcitabine (IA-Gem) in LAPC. The trial is designed with an induction phase where patients receive 3 cycles of Gem-Nab and a cycle of radiation after which they are randomized to IA-Gem or continuing with 4 cycles of Gem-Nab. We studied the resection rate in patients receiving Gem-Nab during induction who had subsequently continued receiving Gem-Nab post-randomization. Results: As of July 2020, 80 patients have been enrolled in the study. From this report, 30 patients were excluded because they had not completed induction and/or active treatment or were randomized to IA-Gem at the time of analysis. From the remaining 50 patients, 5 underwent resection for an overall resection rate of 10%. The median age for the total cohort was 67 years (range 47-83). Most of the resections were performed on the younger cohort of patients under 65 years (median age 60, range 47-65) in whom the resection rate was 4 out of 22 (18.2%). Conclusions: In the younger cohort of patients, TIGeR-PaC results are in line with the 15% resection rate in the LAPACT trial of patients with median age of 65 years, as reported by Phillip et al., 2020. In the TIGeR-PaC study the resection rate for LAPC treated with Gem-Nab was 10% overall, and 18.2% for younger patient population. These resection rates are comparable to the other reports for Gem-Nab and are similar to retrospective reports for the younger patients undergoing resection after treatment with FOLFIRINOX. Clinical trial information: NCT03257033.
Continuing Enasidenib Treatment for Patients with Mutant- IDH2 (m IDH2) Relapsed or Refractory Acute Myeloid Leukemia (R/R AML) with Stable Disease May Result in Improved Survival and Responses over Time
Authors: Eytan M. Stein, Richard M. Stone, Daniel A. Pollyea, Gail J. Roboz, Jessica K. Altman, Courtney D. DiNardo, Stephane de Botton, Nora Tu, Arlene S. Swern, Alessandra Tosolini, Ira Gupta, Samuel V. Agresta, Amir T. Fathi
Journal: Blood (2017)
Almost two thirds of ethnic minority psychiatrists have faced racism at work, survey finds
Authors: Abi Rimmer
Journal: BMJ (2021)

Six in 10 psychiatrists from an ethnic minority background have experienced racism at work, a survey by the Royal College of Psychiatrists has reported. The college called for all mental health staff to undergo mandatory unconscious bias training in the wake of its findings.

Ethnic minority doctors make up 39% of the Royal College of Psychiatrists’ membership, (27% Asian, 6% Black, 2% mixed heritage, and 4% other). The college surveyed members working in the …
Targeting IGF Perturbs Global Replication through Ribonucleotide Reductase Dysfunction
Authors: Guillaume Rieunier, Xiaoning Wu, Letitia E. Harris, Jack V. Mills, Ashwin Nandakumar, Laura Colling, Elena Seraia, Stephanie B. Hatch, Daniel V. Ebner, Lisa K. Folkes, Ulrike Weyer-Czernilofsky, Thomas Bogenrieder, Anderson J. Ryan, Valentine M. Macaulay
Journal: Cancer Research (2021)

Abstract Inhibition of IGF receptor (IGF1R) delays repair of radiation-induced DNA double-strand breaks (DSB), prompting us to investigate whether IGF1R influences endogenous DNA damage. Here we demonstrate that IGF1R inhibition generates endogenous DNA lesions protected by 53BP1 bodies, indicating under-replicated DNA. In cancer cells, inhibition or depletion of IGF1R delayed replication fork progression accompanied by activation of ATR–CHK1 signaling and the intra-S-phase checkpoint. This phenotype reflected unanticipated regulation of global replication by IGF1 mediated via AKT, MEK/ERK, and JUN to influence expression of ribonucleotide reductase (RNR) subunit RRM2. Consequently, inhibition or depletion of IGF1R downregulated RRM2, compromising RNR function and perturbing dNTP supply. The resulting delay in fork progression and hallmarks of replication stress were rescued by RRM2 overexpression, confirming RRM2 as the critical factor through which IGF1 regulates replication. Suspecting existence of a backup pathway protecting from toxic sequelae of replication stress, targeted compound screens in breast cancer cells identified synergy between IGF inhibition and ATM loss. Reciprocal screens of ATM-proficient/deficient fibroblasts identified an IGF1R inhibitor as the top hit. IGF inhibition selectively compromised growth of ATM-null cells and spheroids and caused regression of ATM-null xenografts. This synthetic-lethal effect reflected conversion of single-stranded lesions in IGF-inhibited cells into toxic DSBs upon ATM inhibition. Overall, these data implicate IGF1R in alleviating replication stress, and the reciprocal IGF:ATM codependence we identify provides an approach to exploit this effect in ATM-deficient cancers. Significance: This study identifies regulation of ribonucleotide reductase function and dNTP supply by IGFs and demonstrates that IGF axis blockade induces replication stress and reciprocal codependence on ATM.
Comparative tolerability and efficacy of daylight, conventional, and combination aminolevulinic acid photodynamic therapy for treatment of actinic keratosis
Authors: Lauren D. Crow, Drew Saylor, Kelly Griffith-Bauer, Tiffany Tello, Christine Aroyan, Ann A. Lazar, Sarah T. Arron
Journal: Journal of the American Academy of Dermatology (2021)
Abstract 14300: Elevated T Wave Heterogeneity is Associated With Ventricular Tachyarrhythmia in Mitral Valve Prolapse
Authors: Francesca N Delling, Victor Z de Antonio, Anderson C Silva, Lisa Lim, Bruce D Nearing, Richard L Verrier
Journal: Circulation (2018)

Introduction: Mitral valve prolapse (MVP) has been associated with focal and/or diffuse myocardial fibrosis and ventricular arrhythmia leading to sudden cardiac death (SCD). Suitable ECG methods fo...
Molecular Diversity of Clinically Stable Human Kidney Allografts
Authors: Dmitry Rychkov, Swastika Sur, Marina Sirota, Minnie M. Sarwal
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Clinical decision and immunosuppression dosing in kidney transplantation rely on transplant biopsy tissue histology even though histology has low specificity, sensitivity, and reproducibility for rejection diagnosis. The inclusion of stable allografts in mechanistic and clinical studies is vital to provide a normal, noninjured comparative group for all interrogative studies on understanding allograft injury. <h3>Objective</h3> To refine the definition of a stable allograft as one that is clinically, histologically, and molecularly quiescent using publicly available transcriptomics data. <h3>Design, Setting, and Participants</h3> In this prognostic study, the National Center for Biotechnology Information Gene Expression Omnibus was used to search for microarray gene expression data from kidney transplant tissues, resulting in 38 studies from January 1, 2017, to December 31, 2018. The diagnostic annotations included 510 acute rejection (AR) samples, 1154 histologically stable (hSTA) samples, and 609 normal samples. Raw fluorescence intensity data were downloaded and preprocessed followed by data set merging and batch correction. <h3>Main Outcomes and Measures</h3> The primary measure was area under the receiver operating characteristics curve from a set of feature selected genes and cell types for distinguishing AR from normal kidney tissue. <h3>Results</h3> Within the 28 data sets, the feature selection procedure identified a set of 6 genes (<i>KLF4</i>,<i>CENPJ</i>,<i>KLF2</i>,<i>PPP1R15A</i>,<i>FOSB</i>,<i>TNFAIP3</i>) (area under the curve [AUC], 0.98) and 5 immune cell types (CD4<sup>+</sup>T-cell central memory [Tcm], CD4<sup>+</sup>T-cell effector memory [Tem], CD8<sup>+</sup>Tem, natural killer [NK] cells, and Type 1 T helper [T<sub>H</sub>1] cells) (AUC, 0.92) that were combined into 1 composite Instability Score (InstaScore) (AUC, 0.99). The InstaScore was applied to the hSTA samples: 626 of 1154 (54%) were found to be immune quiescent and redefined as histologically and molecularly stable (hSTA/mSTA); 528 of 1154 (46%) were found to have molecular evidence of rejection (hSTA/mAR) and should not have been classified as stable allografts. The validation on an independent cohort of 6 months of protocol biopsy samples in December 2019 showed that hSTA/mAR samples had a significant change in graft function (<i>r</i> = 0.52,<i>P</i> &lt; .001) and graft loss at 5-year follow-up (<i>r</i> = 0.17). A drop by 10 mL/min/1.73m<sup>2</sup>in estimated glomerular filtration rate was estimated as a threshold in allograft transitioning from hSTA/mSTA to hSTA/mAR. <h3>Conclusions and Relevance</h3> The results of this prognostic study suggest that the InstaScore could provide an important adjunct for comprehensive and highly quantitative phenotyping of protocol kidney transplant biopsy samples and could be integrated into clinical care for accurate estimation of subsequent patient clinical outcomes.
Niche-specific MHC II and PD-L1 regulate CD4+CD8αα+ intraepithelial lymphocyte differentiation
Authors: Sookjin Moon, Yunji Park, Sumin Hyeon, Young-Min Kim, Ji-Hae Kim, Hyekang Kim, Subin Park, Kun-Joo Lee, Bon-Kyoung Koo, Sang-Jun Ha, Seung-Woo Lee
Journal: The Journal of Experimental Medicine (2021)

Conventional CD4+ T cells are differentiated into CD4+CD8αα+ intraepithelial lymphocytes (IELs) in the intestine; however, the roles of intestinal epithelial cells (IECs) are poorly understood. Here, we showed that IECs expressed MHC class II (MHC II) and programmed death-ligand 1 (PD-L1) induced by the microbiota and IFN-γ in the distal part of the small intestine, where CD4+ T cells were transformed into CD4+CD8αα+ IELs. Therefore, IEC-specific deletion of MHC II and PD-L1 hindered the development of CD4+CD8αα+ IELs. Intracellularly, PD-1 signals supported the acquisition of CD8αα by down-regulating the CD4-lineage transcription factor, T helper-inducing POZ/Krüppel-like factor (ThPOK), via the Src homology 2 domain-containing tyrosine phosphatase (SHP) pathway. Our results demonstrate that noncanonical antigen presentation with cosignals from IECs constitutes niche adaptation signals to develop tissue-resident CD4+CD8αα+ IELs.
OP0093 Interferon gamma gene polymorphism: Relationship to susceptibility and severity of rheumatoid arthritis in a prospective study
Authors: A Constantin, F Navaux, V Lauwers-Cancès, M Abbal, JP Van Meerjwijk, B Mazières, A Cambon-Thomsen, A Cantagrel
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Interferon gamma (IFNg) is a multifunctional cytokine that plays an important role in modulating most of the phases of the immune and inflammatory responses. IFNg gene is a potential candidate as marker of rheumatoid arthritis (RA) susceptibility and severity. <h3>Objectives</h3> In this prospective longitudinal study we have investigated the association between a variable length CA repeat in the first intron of the IFNg gene and RA susceptibility and severity. <h3>Methods</h3> One hundred and three early (&lt; 1 year) RA patients (ACR 1987 criteria) were evaluated clinically, serologically and radiographically (modified Sharp/van der Heijde method) yearly for 4 years. The total radiological damage score was used to quantify RA severity after 4 years of follow-up. One hundred thirty unrelated healthy individuals were used as controls. The microsatellite region in the first intron of the IFNg gene was analysed by PCR and electrophoresis in an automatic DNA sequencer. <h3>Results</h3> Characteristics of the 103 RA patients at inclusion were as follows: 80 females, 23 males, mean age 49.4 ± 15.5 years, mean disease duration 6.9 ± 3.7 months, mean tender joint score 12.4 ± 8.9, mean swollen joint number 6 ± 6.2, mean erythrocyte sedimentation rate 29.8 ± 25.2, rheumatoid factor positive (ELISA method) 71/103, mean radiological score 5 ± 13.6. The allele sizes of the IFNg gene polymorphic region ranged from 122 bp (11 CA repeats) to 134 bp (17 CA repeats). Twelve CA repeat (12R) and thirteen CA repeat (13R) alleles were the most common in RA patients (respectively 41.7% and 48.5%) and healthy controls (respectively 45.3% and 45.7%). 12R/12R, 12R/13R and 13R/13R genotypes were the most common in RA patients (respectively 15.6%, 44.1% and 21.6%) and healthy controls (respectively 22.4%, 38.0% and 21.7%). No association has been observed between the IFNg gene polymorphism and RA susceptibility or severity. <h3>Conclusion</h3> Although the present study fails to reveal any association between this particular IFNg gene polymorphism and RA, the search for RA susceptibility and severity genes remains an important issue to better understand RA pathophysiology and to optimise the strategies for treatment of early RA.
Immunisation of healthcare workers in the Nordic countries: Variation in recommendations and practices and a lack of assessment
Authors: Timothee Dub, Bolette Søborg, Peter Henrik Andersen, Thorolfur Gudnason, Hanne Nøkleby, Ann Lindstrand, Rose-Marie Carlsson, Hanna Nohynek
Journal: Eurosurveillance (2021)

Healthcare workers (HCWs) are at increased risk of both exposure and transmission of infectious disease. Two European Union (EU) directives state that health services are responsible for assessing their employees' potential exposure to infectious diseases and offering immunisation free of charge. We assessed current policy for immunisation of HCWs and the availability of vaccine coverage data in the Nordic countries by surveying national vaccination experts in Denmark, Finland, Iceland, Norway and Sweden, as well as Swedish county medical officers (CMOs). All national experts and 17 of 21 Swedish CMOs responded. All EU countries had transposed the European directives into national law, while Norway and Iceland had similar national legislation. Recommendations or guidelines were issued in Denmark, Finland, Iceland, Norway and 15 of 17 responding Swedish counties. The range of diseases covered differed by countries and Swedish counties. HCW vaccine coverage data were not systematically collected; incomplete estimates were only available for Finland and two Swedish counties. In conclusion, recommendations or guidelines exist in the Nordic countries, but their impact cannot be assessed, as vaccine uptake among HCWs is not currently measured. Systematic collection of data is a necessary step towards improving HCW immunisation policy and practice in the Nordic countries.
FRI0006 Double-blind clinical, laboratory and ultrasound assessment of the efficacy of antibodies to interferon-g (anti-ifn-g) in rheumatoid arthritis (ra)
Authors: GV Loukina, YA Sigidin, OV Pushkova, ES Mach, SV Skurkovich, BS Skurkovich
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To objectively assess the efficacy and tolerability of anti-IFN-g in treating patients with active RA. <h3>Methods</h3> Thirty patients with active RA were randomly assigned to receive intramuscularly injections of anti-IFN-g, antibodies to tumour necrosis factor a (anti-TNF) or placebo for 5 consecutive days (10 patients on each treatment regimen). The patients were clinically assessed daily for 7 days, then weekly up to the 28-th day. Clinical, laboratory and ultrasound indices were used for the evaluation of the treatment efficacy. <h3>Results</h3> Both anti-cytokines were equally effective and significantly superior to placebo. Twelve patients stopped treatment due to the lack of efficacy: 1 on anti-TNF, 2 on anti-IFN-g and 9 on placebo. According to the physician?s assessment improvement was achieved by the 7-th day on anti-TNF in 9 patients, on anti-IFN-g in 7, and on placebo in 2. At the 28-th day the corresponding figures were 8, 8, and 0, respectively. By the 28-th day each of the anti-cytokine groups showed significant improvement in 5 clinical measures including numbers of swollen and painful joints, pain and fatigue. The single patient in the placebo group who completed the trial had no positive changes in the disease activity. The thickness of the inflamed synovial membrane assessed by the ultrasound method decreased significantly only on anti-IFN-g (both by the 7-th and by the 28-th days). <h3>Conclusion</h3> The results obtained suggest that IFN-g plays an important role in the pathogenesis of RA. The use of antibodies to this cytokine can be considered as a promising approach to the therapy of RA, especially its treatment-resistant forms.