tbuckley/cabot-search huggingface dataset:
<i>Notes from the Field:</i> Effects of the COVID-19 Response on Tuberculosis Prevention and Control Efforts — United States, March–April 2020
Authors: Ann M. Cronin, Shanica Railey, Diana Fortune, Donna Hope Wegener, Justin B. Davis
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

This article reported the effects of public health response to COVID-19 to tuberculosis prevention and control  The COVID-19 response has affected multiple sectors of public health, recommended preventive screening, and clinical care  The United States will need to address the backlog of population health services that have been delayed or not done while public health resources are focused on COVID-19  The U S  domestic TB elimination program is one example  If essential TB program activities are not sustained, gains made in reducing U S  TB cases will be at risk  CDC has published guidance regarding non-COVID-19 public health activities that require physical interaction with clients  CDC will support grantees by providing technical assistance or outbreak response, when requested  NTCA will continue to communicate with members and share best practices for averting a resurgence of TB
Nanomicelle protects the immune activation effects of Paclitaxel and sensitizes tumors to anti-PD-1 Immunotherapy
Authors: Qianmei Yang, Gang Shi, Xiaolei Chen, Yi Lin, Lin Cheng, Qingyuan Jiang, Xi Yan, Ming Jiang, Yiming Li, Hantao Zhang, Huiling Wang, Yuan Wang, Qingnan Wang, Yujing Zhang, Yi Liu, Xiaolan Su, Lei Dai, Minghai Tang, Jia Li, Lan Zhang, Zhiyong Qian, Dechao Yu, Hongxin Deng
Journal: Theranostics (2020)

Paclitaxel (PTX) has shown pleiotropic immunologic effects on the tumor microenvironment, and nanomicelle has emerged as a promising strategy for PTX delivery. However, the detailed mechanisms remain to be fully elucidated. Meanwhile, immunogenic cell death (ICD) is an effective approach to activate the immune system. This study investigated the ICD effect of PTX and how nanomicelle affected the immune-activation ability of PTX. Methods: The ICD effects of PTX were identified via the expression of ICD markers and cell vaccine experiment. Tumor size and overall survival in multiple animal models with treatment were monitored to evaluate the antitumor effects. The mechanisms of PTX-induced ICD and antitumor immunity were determined by detecting gene expression related to ER stress and analyzing immune cell profile in tumor after treatment. Results: We revealed the immune-regulation mechanism of PTX nanomicelle by inducing ICD, which can promote antigen presentation by dendritic cells (DCs) and activate antitumor immunity. Notably, nanomicelle encapsulation protected the ICD effects and immune activation, which were hampered by immune system impairment caused by chemotherapy. Compared with traditional formulations, a low dose of nanomicelle-encapsulated PTX (nano-PTX) treatment induced immune-dependent tumor control, which increased the infiltration and function of both T cells and DCs within tumors. However, this antitumor immunity was hampered by highly expressed PD-1 on tumor-infiltrating CD8+ T cells and upregulated PD-L1 on both immune cells and tumor cells after nano-PTX treatment. Combination therapy with a low dose of nano-PTX and PD-1 antibodies elicited CD8+ T cell-dependent antitumor immunity and remarkably improved the therapeutic efficacy. Conclusions: Our results provide systemic insights into the immune-regulation ability of PTX to induce ICD, which acts as an inducer of endogenous vaccines through ICD effects, and also provides an experimental basis for clinical combination therapy with nano-PTX and PD-1 antibodies.
THU0188 Frequency of autoantibodies targeting pancreas in rheumatoid arthritis with and without secondary sjÖgren’s syndrome
Authors: A Isik, E Tunc, G Kitapcýoglu, H Kocanaogullarý, V Inal, E Doganavsargil, G Gumusdis
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Immune mediated diseases may be tissue specific such as insulin dependent diabetes mellitus (IDDM), or may be systemic such as rheumatoid arthritis (RA). Since impaired glucose tolerance have been reported in some connective tissue diseases.<sup>1,2</sup> <h3>Objectives</h3> we investigated the frequency of autoantibodies targeting pancreas in RA patients with and without Sjögren's syndrome (SjS). <h3>Methods</h3> 103 RA patients, 26 with secondary SjS were included in this study. Serum islet cell antibodies (ICA), anti-insulin antibodies (AIA) and insulin receptor antibodies (IRA) were measured. Standard oral glucose tolerance test was performed if fasting or postprandial plasma glucose levels were elevated, or if any of the above mentioned antibodies were positive. <h3>Results</h3> The frequencies of positive ICA, AIA and IRA in the whole group of patients with RA were 21.4%, 29.7% and 15.2%, respectively. There was no significant differences between the subgroups of RA patients with respect to OGTT results and autoantibodies (p &gt; 0.05). However, we observed a significant difference between AIA positivity and disease duration (p &lt; 0.05). <h3>Conclusion</h3> Presence of autoantibodies targeting pancreas does not differ significantly in RA patients with and without SjS. These antibodies are not specific for IDDM, rather they are part of the autoimmune repertoire in systemic autoimmune diseases such as RA. <h3>References</h3> Paolisso G, Valentini G, Giugliano D, <i>et al</i>. Evidence for peripheral impaired glucose handling in patients with connective tissue diseases. Metabolism 1991;40(9):902–7 Thomas DJ, Young A, Gorsuch AN, <i>et al</i>. Evidence for an association between rheumatoid arthritis and autoimmune endocrine diseases. Ann Rheum Dis. 1983;42(3):297–300
Evaluation of Predictors of Outcome in Immune Tolerance Induction Treatment of Hemophilia Α Patients with High-Responding Inhibitors
Authors: Alessandra N L Prezotti, Clarissa Ferreira, Luciana Oliveira, Claudia Lorenzato, Maria P S V Orletti, Maria do Rosario Roberti, Rosangela Ribeiro, Paula Ribeiro Villaca, Silmara Aparecida De Lima Montalvão, Samuel S Medina, Gabriela G Yamaguti Hayakawa, Margareth C Ozelo
Journal: Blood (2017)
Lentivirus-mediated IL-10-expressing Bone Marrow Mesenchymal Stem Cells promote corneal allograft survival <i>via</i> upregulating lncRNA 003946 in a rat model of corneal allograft rejection
Authors: Xiaoxiao Lu, Yusha Ru, Chenchen Chu, Ying Lv, Yichen Gao, Zhe Jia, Yue Huang, Yan Zhang, Shaozhen Zhao
Journal: Theranostics (2020)

Rationale: Corneal transplantation is an effective treatment to corneal blindness. However, the immune rejection imperils corneal allograft survival. An interventional modality is urgently needed to inhibit immune rejection and promote allograft survival. In our previous study, subconjunctival injections of bone marrow-derived mesenchymal stem cells (BM-MSCs) into a rat model of corneal allograft rejection extended allograft survival for 2 d. In this study, we sought to generate IL-10-overexpressing BM-MSCs, aiming to boost the survival-promoting effects of BM-MSCs on corneal allografts and explore the molecular and cellular mechanisms underlying augmented protection. Methods: A population of IL-10-overexpressing BM-MSCs (designated as IL-10-BM-MSCs) were generated by lentivirus transduction and FACS purification. The self-renewal, multi-differentiation, and immunoinhibitory capabilities of IL-10-BM-MSCs were examined by conventional assays. The IL-10-BM-MSCs were subconjunctivally injected into the model of corneal allograft rejection, and the allografts were monitored on a daily basis. The expression profiling of long noncoding RNA (lncRNA) in the allografts was revealed by RNA sequencing and verified by quantitative real-time PCR. The infiltrating immune cell type predominantly upregulating the lncRNA expression was identified by RNAscope in situ hybridization. The function of the upregulated lncRNA was proved by loss- and gain-of-function experiments both in vivo and in vitro. Results: The IL-10-BM-MSCs possessed an enhanced immunoinhibitory capability and unabated self-renewal and multi-differentiation potentials as compared to plain BM-MSCs. The subconjunctivally injected IL-10-BM-MSCs reduced immune cell infiltration and doubled allograft survival time (20 d) as compared to IL-10 protein or plain BM-MSCs in the corneal allograft rejection model. Further, IL-10-BM-MSCs significantly upregulated lncRNA 003946 expression in CD68+ macrophages infiltrating corneal allografts. Silencing and overexpressing lncRNA 003946 in macrophage cultures abolished and mimicked the IL-10-BM-MSCs' suppressing effects on the macrophages' antigen presentation, respectively. In parallel, knocking down and overexpressing the lncRNA in vivo abrogated and simulated the survival-promoting effects of IL-10-BM-MSCs on corneal allografts, respectively. Conclusion: The remarkable protective effects of IL-10-BM-MSCs support further developing them into an effective interventional modality against corneal allograft rejection. IL-10-BM-MSCs promote corneal allograft survival mainly through upregulating a novel lncRNA expression in graft-infiltrating CD68+ macrophages. LncRNA, for the first time, is integrated into an IL-10-BM-MSC-driven immunomodulatory axis against the immune rejection to corneal allograft.
CLINICAL FEATURES AND OUTCOMES IN AN INTERNATIONAL COHORT OF 731 ALAGILLE SYNDROME PATIENTS FROM 19 COUNTRIES
Authors: Shannon Vandriel, Jian-She Wang, Liting Li, David A Piccoli, Kathleen M Loomes, Etienne M Sokal, Tanguy Demaret, Henrik Arnell, Bjorn Fischler, Rima L Fawaz, Silvia Nastasio, Winita Hardikar, Sahana Shankar, Way S Lee, Chatmanee Lertudomphonwanit, Wikrom Karnsakul, Saul J Karpen, Ryan T Fischer, Ruben E Quiros, Melina Melere, Luis Bujanda, Giuseppe Indolfi, Emanuele Nicastro, Pier Luigi Calvo, Pamela L Valentino, Kathleen B Schwarz, Ino Kanavaki, Antal Dezsofi, Quais Mujawar, Raquel B Pinto, Jernej Brecelj, Nanda Kerkar, Maria-Camila Sanchez, Palaniswamy Karthikeyan, Ermelinda Santos-Silva, Carolina Jimenez-Rivera, Yael Mozer-Glassberg, Seema Alam, Bettina E Hansen, Binita M Kamath
Journal: Hepatology (2019)
HP0015 Bone turnover during pregnancy in women with low dietary calcium intake: effects of a calcium citrate supplement
Authors: NJ Aparicio, MA Joao, S Bernacchi, S Gimenez, V Carames, DM Galimberti
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Objective</h3> To determine parameters of calcium homeostasis in pregnant women with low dietary calcium intake and to observe the effects of a calcium supplement. <h3>Method</h3> 44 pregnant women (calcium intake: 310 to 720 mg/day) were enrolled. Blood and urine samples were taken around the 20th. week (pre-treatment value). Afterwards 26 women received calcium 750 mg/day (as calcium citrate suspension) until delivery; 18 received a placebo. At 36th–38th week blood and urine samples were again taken (post-treatment value). Ca and P in serum and urine and serum bone -specific alkaline phosphatase (AP), intact PTH, 1,25–2OH-vit D, IGF-1 and degradation products of C terminal telopeptides of type I collagen (CT) were determined. <h3>Results</h3> At enrollment serum Ca, P, AP and IGF-1 were normal although with a great individual variation for IGF-1 (50% of the women showed high values and 20% low values); PTH (103.8 ± 56.4 pg/ml), CT (4855 ± 268 pM) and 1.25–2OH-vit D (46.8 ± 7.4 pg/ml) showed high values. After treatment the calcium-treated women showed a significant decrease of AP (15.7 ± 3.3 U/l), PTH (35.8 ± 25.8 pg/ml), CT (2490 ± 1498 pM) and 1,25–2OH-vitD (38.0 ± 8.0 pg/ml) while the other parameters remained without significant changes. The placebo-group showed increments of AP, PTH, CT and 1.25–2OH-vitD. <h3>Conclusions</h3> In pregnant women with low dietary Ca intake a parathyroid hyperfunction is present at least at the 20th week of pregnancy, a situation reverted by calcium supplement. In contrast to other studies IGF-1 did not show a systematic increase.
AB0203 A case with spinal brucellosis and lumbar disc herniation
Authors: R Celiker, S Bal
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Human Brucellosis is a zoonosis and endemic in Mediterranean area. Localised osteoarticular manifestations of brucellosis include spondylitis, sacroiliitis, mono/oligoarthritis and bursitis. Coexistence of lumbar intervertebral disc herniation in spondylitis cases which do not have fever and constitutional symptoms, however, makes the diagnosis challenging. <h3>Objectives</h3> We describe a patient with brucella spondylitis accompanying L4–5 and L5-S1 herniated nucleus pulposus (HNP). <h3>Methods</h3> A 50 year old woman admitted to our outpatient clinic with low back pain, radiating to the lateral aspect of the left thigh lasting for 3 weeks. She did not have any history of fever, chills and constitutional symptoms. On physical examination, she was afebrile and only had tenderness over the lumbosacral region. The neurological examination revealed hypoesthesia in the right lower extremity overlapping the L5 dermatome. Straight leg raising test was positive on the right side. <h3>Results</h3> Laboratory values were as follows: erythrocyte sedimentation rate 16 mm/hr, leucocyte count 4600/mm3, haemoglobin 10.4 gr/dl, C-reactive protein 0.143 mg/dl. Hepatic and renal function tests were normal. Seroagglutination test for brucella was 1/640. Plain radiography of the lumbar region revealed L5 spondylolisthesis and narrowed disc space between L5-S1 vertebrae. Magnetic resonance imaging (MRI) disclaimed L5 spondylolisthesis, spondylolysis, L5-S1 discitis, L5-S1 HNP, bilateral foraminal stenosis and L4-L5 minimal posterior protrusion. Total body bone scan with Tc-99m sulfur colloid revealed increased uptake at the superior region of the sacrum. Oral treatment with doxycycline and rifampin was started. There was overt clinical improvement after combined antibiotic regimen for 6 weeks. After a symptom-free period of 7 weeks a relapse occurred. An oral regimen of rifampin and ofloxacin was started again. Following up with the antibiotic therapy and immobilisation with rigid lumbosacral brace, she had a dramatic reduction in low back pain and she had regressive findings of the lesion in the control MRI. <h3>Conclusion</h3> In some areas where brucellosis is rarely seen, due to non-spesific clinical picture and low index of suspicion, disease can easily be misdiagnosed. Spinal brucellosis can be confused with disc herniation, leading to inappropriate treatment and increased morbidity. In endemic regions, coexistence with lumbar disc herniation, like in our patient, should always be in mind of the physician and clinically, diagnosing of herniation alone should not seem satisfactory all the time.
Changes to Visitation Policies and Communication Practices in Michigan ICUs during the COVID-19 Pandemic
Authors: Thomas S. Valley, Amanda Schutz, Max T. Nagle, Lewis J. Miles, Kyra Lipman, Scott W. Ketcham, Madison Kent, Clarice E. Hibbard, Emily A. Harlan, Katrina Hauschildt
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Different eGFR Decline Thresholds and Renal Effects of Canagliflozin: Data from the CANVAS Program
Authors: Megumi Oshima, Bruce Neal, Tadashi Toyama, Toshiaki Ohkuma, Qiang Li, Dick de Zeeuw, Hiddo J.L. Heerspink, Kenneth W. Mahaffey, Gregory Fulcher, William Canovatchel, David R. Matthews, Vlado Perkovic
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Traditionally, clinical trials studying effects of new therapies on renal outcome use the doubling of serum creatinine (equivalent to a 57% eGFR reduction) as an end point, requiring large sample sizes. Use of lesser eGFR reductions has been proposed, but few studies have evaluated their reliability. In this post hoc study of two multicenter, randomized trials, a greater number of observed events resulted from use of 50%, 40%, and 30% eGFR reductions compared with a 57% eGFR reduction. Observed effect sizes for canagliflozin versus placebo were attenuated when lesser eGFR reductions were used, likely because of canagliflozin’s acute effect on eGFR. However, if analyses control for this acute effect, lesser eGFR decline thresholds may be preferred to identify renoprotective effects of potential therapies because much smaller sample sizes can be used. Background Traditionally, clinical trials evaluating effects of a new therapy with creatinine-based renal end points use doubling of serum creatinine (equivalent to a 57% eGFR reduction), requiring large sample sizes. Methods To assess whether eGFR declines &lt;57% could detect canagliflozin’s effects on renal outcomes, we conducted a post hoc study comparing effects of canagliflozin versus placebo on composite renal outcomes using sustained 57%, 50%, 40%, or 30% eGFR reductions in conjunction with ESKD and renal death. Because canagliflozin causes an acute reversible hemodynamic decline in eGFR, we made estimates using all eGFR values as well as estimates that excluded early measures of eGFR influenced by the acute hemodynamic effect. Results Among the 10,142 participants, 93 (0.9%), 161 (1.6%), 352 (3.5%), and 800 (7.9%) participants recorded renal outcomes on the basis of 57%, 50%, 40%, or 30% eGFR reduction, respectively, during a mean follow-up of 188 weeks. Compared with a 57% eGFR reduction (risk ratio [RR], 0.51; 95% confidence interval [95% CI], 0.34 to 0.77), the effect sizes were progressively attenuated when using 50% (RR, 0.61; 95% CI, 0.45 to 0.83), 40% (RR, 0.70; 95% CI, 0.57 to 0.86), or 30% (RR, 0.81; 95% CI, 0.71 to 0.93) eGFR reductions. In analyses that controlled for the acute hemodynamic fall in eGFR, effect sizes were comparable, regardless of whether a 57%, 50%, 40%, or 30% eGFR reduction was used. Estimated sample sizes for studies on the basis of lesser eGFR reductions were much reduced by controlling for this early hemodynamic effect. Conclusions Declines in eGFR &lt;57% may provide robust estimates of canagliflozin’s effects on renal outcomes if the analysis controls for the drug’s acute hemodynamic effect. Clinical Trial registry name and registration number: CANagliflozin cardioVascular Assessment Study (CANVAS), NCT01032629 and CANVAS-R, NCT01989754.
Abstract 11078: Molecular Basis of Obesity Cardiomyopathy in a High-Fat-Diet Rat Model: Contrasting Changes Between Cardiac Beta1-Adrenergic Receptors, SERCA2a and Cardiac Beta3-Adrenergic Receptors
Authors: Zhe Chen, Nadeem Wajih, Heng-Jie Cheng, Tiankai Li, Qun Shao, Michael F Callahan, Che Ping Cheng
Journal: Circulation (2018)

Background: Obesity is associated with the development of cardiomyopathy. However, the mechanism is unclear. Although recent evidence links altered β-adrenergic regulation with obese (OB) cardiomyo...
Molecular signatures of BRCAness analysis identifies PARP inhibitor Niraparib as a novel targeted therapeutic strategy for soft tissue Sarcomas
Authors: Hongyi Li, Jian Tu, Zhiqiang Zhao, Lijuan Chen, Yueting Qu, Hongbo Li, Hao Yao, Xiaoshuai Wang, Dung-Fang Lee, Jingnan Shen, Lili Wen, Gang Huang, Xianbiao Xie
Journal: Theranostics (2020)

Background: Patients with advanced soft tissue sarcomas (STS) have a dismal prognosis with few effective therapeutic options. A defect in the homologous recombination repair (HRR) pathway can accumulate DNA repair errors and gene mutations, which can lead to tumorigenesis. BRCAness describes tumors with an HRR deficiency (HRD) in the absence of a germline BRCA1/2 mutation. However, the characteristics of BRCAness in STS remain largely unknown. Thus, this study aimed to explore the genomic and molecular landscape of BRCAness using whole exome sequencing (WES) in STS, aiming to find a potential target for STS treatment. Methods: WES was performed in 22 STS samples from the First Affiliated Hospital of Sun Yat-sen University to reveal the possible genomic and molecular characteristics. The characteristics were then validated using data of 224 STS samples from The Cancer Genome Atlas (TCGA) database and in vitro data. The analysis of the potential biomarker for BRCAness was performed. Targeted drug susceptibility and combination therapy screening of chemotherapeutics for STS were evaluated in STS cell lines, cell-line-derived xenografts (CDX), and patient-derived xenografts (PDX). Results: Compared with 30 somatic mutation signatures of cancers, high cosine-similarity (0.75) was identified for HRD signatures in the 22 STS samples using nonnegative matrix factorization. Single nucleotide polymorphism indicated a low mutation rate of BRCA1/2 in the 22 STS samples (11.76% and 5.88%, respectively). However, copy number variation analyses demonstrated widespread chromosomal instability; furthermore, 54.55% of STS samples (12/22) carried BRCAness traits. Subsequently, similar genomic and molecular characteristics were also detected in the 224 STS samples from TCGA and in vitro. Poly (ADP-ribose) polymerases (PARP)-1 could be a promising reflection of HRD and therapeutic response. Furthermore, the level of PAR formation was found to be correlated with PARP-1. Subsequently, STS cell lines were determined to be sensitive to PARP inhibitor (PARPi), niraparib. Moreover, based on the screening test of the five common PARPis and combination test among doxorubicin, ifosfamide, dacarbazine, and temozolomide (TMZ), niraparib and TMZ were the most synergistic in STS cell lines. The synergistic effect and safety of niraparib and TMZ combination were also shown in CDX and PDX. Conclusions: BRCAness might be the common genomic and molecular characteristics of majority of STS cases. PARP-1 and PAR could be potential proper and feasible theranostic biomarkers for assessing HRD in patients. STSs were sensitive to PARPi. Moreover, the combination of niraparib and TMZ showed synergistic effect. Niraparib and TMZ could be a promising targeted therapeutic strategy for patients with STS.
Evaluating the Role of Lower Dose Dasatinib in Newly Diagnosed Early Chronic Phase-Chronic Myeloid Leukemia (CML-CP)
Authors: Kiran Naqvi, Jorge E. Cortes, Jeffrey Skinner, Elias J. Jabbour, Naveen Pemmaraju, Prithviraj Bose, Philip A Thompson, Gautam Borthakur, Zeev Estrov, Hagop M. Kantarjian
Journal: Blood (2017)
Spot urinary citrate-to-creatinine ratio is a marker for acid-base status in chronic kidney disease
Authors: Fabiola G. Gianella, Victor E. Prado, John R. Poindexter, Beverley Adams-Huet, Xilong Li, R. Tyler Miller, Khashayar Sakhaee, Naim M. Maalouf, Orson W. Moe
Journal: Kidney International (2020)
Salvage autologous transplant and lenalidomide maintenance vs. lenalidomide/dexamethasone for relapsed multiple myeloma: the randomized GMMG phase III trial ReLApsE
Authors: Hartmut Goldschmidt, Marc-Andrea Baertsch, Jana Schlenzka, Natalia Becker, Christina Habermehl, Thomas Hielscher, Marc-Steffen Raab, Jens Hillengass, Sandra Sauer, Carsten Müller-Tidow, Steffen Luntz, Anna Jauch, Dirk Hose, Anja Seckinger, Peter Brossart, Martin Goerner, Stefan Klein, Martin Schmidt-Hieber, Peter Reimer, Ullrich Graeven, Roland Fenk, Mathias Haenel, Hans Martin, Hans W. Lindemann, Christoph Scheid, Axel Nogai, Hans Salwender, Richard Noppeney, Britta Besemer, Katja Weisel
Journal: Leukemia (2020)