tbuckley/cabot-search huggingface dataset:
Targeting antigens to the human mannose receptor expressed in transgenic mice elicits potent CD4 and CD8 responses in vivo
Authors: Lizhen He, Andrea Crocker, Laura Vitale, Thomas O’Neill, Raphael Clynes, Tibor Keler
Journal: Cancer Research (2006)

1419  Cellular responses, and in particular, cytolitic T cell responses, are critical for the efficacy of most therapeutic cancer vaccines. Our approach to enhancing the cross-presentation of exogenously provided tumor associated antigens (TAA), involves targeting these antigens to dendritic cells and macrophages for efficient uptake, processing, and presentation. We have previously demonstrated that TAA linked to a human mAb specific for the human mannose receptor (hMR) are effectively presented by MHC class I and class II on human dendritic cells in vitro. Moreover, using transgenic mice engineered to express hMR, we have demonstrated that administration of the MR-targeted vaccines resulted in an efficient MR-mediated antigen loading into MR-expressing cells and a rapid, potent and adjuvant-independent humoral response. Here we have further exploited the use of the hMR transgenic mice to investigate the induction of antigen-specific CD4 and CD8 T cell responses after immunization with MR-targeted vaccines. hMR-expressing mice immunized with a fusion protein consisting of the anti-hMR mAb (B11) and the TAA, human chorionic gonadotropin b-subunit (hCGβ) resulted in significantly greater hCGβ-specific T cells secreting IL-4 or IFN-γ than control mice immunized with the vaccine. The magnitude and polarization of the response was influenced by combination with adjuvants. Using CpG alone or in combination with other toll-like receptor ligands as adjuvant, such as polyI:C and HKLP, led to Th1 polarization and promoted antigen-specific T cell activation, as illustrated by increasing IFNγ ELISPOT number and positive intracellular staining of granzyme B. In vivo enhancement of MHC class I presentation was further investigated using ovalbumin (OVA) chemically coupled to the B11 mAb and the OVA-specific OT-I CD8 transgenic T cells. Injection of low doses of B11-OVA triggered efficient OT-I cell proliferation in hMR-Tg. In contrast, similar concentrations of B11-OVA induce little or no proliferation of OT-I cells in wild type mice. These data, demonstrating induction of T cell responses in vivo are consistent with our previous in vitro studies demonstrating that delivering antigens to dendritic cells via an MR-specific antibody results in cross presentation of antigen-derived epitopes by accessing both the Class I and Class II pathways and offers potential for therapeutic intervention of cancers.
National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13–17 Years — United States, 2019
Authors: Laurie D. Elam-Evans, David Yankey, James A. Singleton, Natalie Sterrett, Lauri E. Markowitz, Charnetta L. Williams, Benjamin Fredua, Lucy McNamara, Shannon Stokley
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Three vaccines are recommended by the Advisory Committee on Immunization Practices (ACIP) for routine vaccination of adolescents aged 11-12 years to protect against 1) pertussis; 2) meningococcal disease caused by types A, C, W, and Y; and 3) human papillomavirus (HPV)-associated cancers (1). At age 16 years, a booster dose of quadrivalent meningococcal conjugate vaccine (MenACWY) is recommended. Persons aged 16-23 years can receive serogroup B meningococcal vaccine (MenB), if determined to be appropriate through shared clinical decision-making. CDC analyzed data from the 2019 National Immunization Survey-Teen (NIS-Teen) to estimate vaccination coverage among adolescents aged 13-17 years in the United States.* Coverage with ≥1 dose of HPV vaccine increased from 68.1% in 2018 to 71.5% in 2019, and the percentage of adolescents who were up to date† with the HPV vaccination series (HPV UTD) increased from 51.1% in 2018 to 54.2% in 2019. Both HPV vaccination coverage measures improved among females and males. An increase in adolescent coverage with ≥1 dose of MenACWY (from 86.6% in 2018 to 88.9% in 2019) also was observed. Among adolescents aged 17 years, 53.7% received the booster dose of MenACWY in 2019, not statistically different from 50.8% in 2018; 21.8% received ≥1 dose of MenB, a 4.6 percentage point increase from 17.2% in 2018. Among adolescents living at or above the poverty level,§ those living outside a metropolitan statistical area (MSA)¶ had lower coverage with ≥1 dose of MenACWY and with ≥1 HPV vaccine dose, and a lower percentage were HPV UTD, compared with those living in MSA principal cities. In early 2020, the coronavirus disease 2019 (COVID-19) pandemic changed the way health care providers operate and provide routine and essential services. An examination of Vaccines for Children (VFC) provider ordering data showed that vaccine orders for HPV vaccine; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap); and MenACWY decreased in mid-March when COVID-19 was declared a national emergency (Supplementary Figure 1, https://stacks.cdc.gov/view/cdc/91795). Ensuring that routine immunization services for adolescents are maintained or reinitiated is essential to continuing progress in protecting persons and communities from vaccine-preventable diseases and outbreaks.
More than loss of taste and smell: burning watering eyes in coronavirus disease 2019
Authors: Alexander C. Rokohl, Niklas Loreck, Philomena A. Wawer Matos, Sarah Zwingelberg, Max Augustin, Felix Dewald, Rafael S. Grajewski, Florian Klein, Clara Lehmann, Ludwig M. Heindl
Journal: Clinical Microbiology and Infection (2020)
Therapeutic plasma exchange clears circulating soluble PD-L1 and PD-L1-positive extracellular vesicles
Authors: Jacob J Orme, Elizabeth Ann L Enninga, Fabrice Lucien-Matteoni, Heather Dale, Edwin Burgstaler, Susan M Harrington, Matthew K Ball, Aaron S Mansfield, Sean S Park, Mathew S Block, Svetomir N Markovic, Yiyi Yan, Haidong Dong, Roxana S Dronca, Jeffrey L Winters
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Trans-acting programmed death-ligand 1 (PD-L1) derives from malignant cells in three known forms. High levels of secreted splice variant PD-L1 (sPD-L1), ADAM10/ADAM17-shed sPD-L1, and PD-L1-positive extracellular vesicles (evPD-L1) each predict poor prognosis and limited response to PD-(L)1 checkpoint inhibitors in cancer. To our knowledge, no clinical intervention has reduced any of these circulating forms of extracellular PD-L1. Here, we explore therapeutic plasma exchange (TPE) as a treatment to reduce circulating extracellular PD-L1. Results In patients with melanoma, sPD-L1 levels above 0.277 ng/mL predicted inferior overall survival. In patients undergoing TPE for non-malignant indications, each TPE session removed a mean 70.8% sPD-L1 and 73.1% evPD-L1 detectable in plasma. TPE also reduced total and ADAM10-positive extracellular vesicles. Conclusion Here, we report the first known clinical intervention to remove either sPD-L1 or evPD-L1 from plasma in vivo. TPE reduces plasma sPD-L1 and evPD-L1 in vivo and may have a role in treatment with immunotherapy. TPE may also prove useful in patients with other extracellular vesicle-related conditions.
Incremental Value of 3D Printing in the Preoperative Planning of Complex Congenital Heart Disease Surgery
Authors: Dong Hyun Yang, Sang-Hyub Park, Namkug Kim, Eun Seok Choi, Bo Sang Kwon, Chun Soo Park, Seul Gi Cha, Jae Suk Baek, Jeong Jin Yu, Young-Hwue Kim, Tae-Jin Yun
Journal: JACC. Cardiovascular imaging (2020)
Real-world effectiveness of rotavirus vaccines, 2006–19: a literature review and meta-analysis
Authors: Eleanor Burnett, Umesh D Parashar, Jacqueline E Tate
Journal: The Lancet Global Health (2020)

Since licensure in 2006, rotavirus vaccines have been introduced in more than 100 countries. The efficacy of rotavirus vaccines is variable in settings with different child mortality levels. We did an updated review of the published literature to assess the real-world effectiveness of rotavirus vaccines in a range of settings.In this literature review and meta-analysis, we included observational, post-licensure studies of rotavirus vaccines, published from Jan 1, 2006, to Dec 31, 2019, in English, with laboratory-confirmed rotavirus as the endpoint. In addition to product-specific results for Rotarix (GlaxoSmithKline Biologicals, Rixensart, Belgium) or RotaTeq (Merck, West Point, PA, USA), we included Rotarix and RotaTeq mixed series, and non-product-specific vaccine effectiveness estimates from countries where Rotarix and RotaTeq are both available. Studies of other infant rotavirus vaccines were excluded because little or no post-licensure data were available. We fitted random-effects regression models to estimate vaccine effectiveness among children younger than 12 months and aged 12-23 months. On the basis of 2017 UNICEF mortality estimates for children younger than 5 years, countries were stratified as having low (lowest quartile), medium (second quartile), or high mortality (third and fourth quartiles).We identified and screened 1703 articles, of which 60 studies from 32 countries were included. 31 studies were from countries with low child mortality, eight were from medium-mortality countries, and 21 were from high-mortality countries. Rotarix vaccine effectiveness against laboratory-confirmed rotavirus among children younger than 12 months old was 86% (95% CI 81-90) in low-mortality countries, 77% (66-85) in medium-mortality countries, and 63% (54-70) in high-mortality countries. Rotarix vaccine effectiveness among children aged 12-23 months was 86% (81-90) in low-mortality countries, 54% (23-73) in medium-mortality countries, and 58% (38-72) in high-mortality countries. RotaTeq vaccine effectiveness among children younger than 12 months was 86% (76-92) in low-mortality countries and 66% (51-76) in high-mortality countries. RotaTeq vaccine effectiveness among children aged 12-23 months was 84% (79-89) in low-mortality countries. There was no substantial heterogeneity (I2 range: 0-36%). Median vaccine effectiveness in low-mortality countries was similar for Rotarix (83%; IQR 78-91), RotaTeq (85%; 81-92), mixed series (86%; 70-91), and non-product-specific (89%; 75-91) vaccination.Rotavirus vaccines were effective in preventing rotavirus diarrhoea, with higher performance in countries with lower child mortality.None.
Efficacy and Safety of Short- and Long-Acting Glucagon-Like Peptide 1 Receptor Agonists on a Background of Basal Insulin in Type 2 Diabetes: A Meta-analysis
Authors: Jessica A. Huthmacher, Juris J. Meier, Michael A. Nauck
Journal: Diabetes Care (2020)

To compare the efficacy and safety of short- and long-acting glucagon-like peptide 1 receptor agonists (GLP-1 RAs), both used in combination with basal insulin, in patients with type 2 diabetes.Randomized controlled trials comparing the coadministration of short- or long-acting GLP-1 RAs and basal insulin with basal insulin ± placebo were identified (PubMed search). Of 974 identified publications, 14 clinical trials were included. Eight trials examined short-acting and six long-acting GLP-1 RAs.Differences in HbA1c, fasting plasma glucose, body weight, and adverse events were compared between studies using short- or long-acting GLP-1 RAs by random-effects meta-analysis.There were relatively small numbers of available publications, some heterogeneity regarding protocols, and differences in the GLP-1 RA compound used.Long-acting GLP-1 RAs more effectively reduced HbA1c (∆ -6 mmol/mol [95% CI -10; -2], P = 0.007), fasting plasma glucose (∆ -0.7 mmol/L [-1.2; -0.3], P = 0.007), and body weight (∆ -1.4 kg [-2.2; -0.6], P = 0.002) and raised the proportion of patients achieving an HbA1c target <7.0% (<53 mmol/mol) (P = 0.03) more than the short-acting ones. Patients reporting symptomatic (P = 0.048) but not severe (P = 0.96) hypoglycemia were fewer with long- versus short-acting GLP-1 RAs added to insulin. A lower proportion of patients reported nausea (-52%, P < 0.0001) or vomiting (-36%, P = 0.0002) with long-acting GLP-1 RAs. Overall, GLP-1 RAs improved HbA1c, fasting plasma glucose, and body weight when added to basal insulin. However, long-acting GLP-1 RAs were significantly more effective for glycemic and body weight control and displayed better gastrointestinal tolerability.
OCT and CMR for the Diagnosis of Patients Presenting With MINOCA and Suspected Epicardial Causes
Authors: Edouard Gerbaud, Fabien Arabucki, Hubert Nivet, Christophe Barbey, Laura Cetran, Stephan Chassaing, Benjamin Seguy, Arnaud Lesimple, Hubert Cochet, Michel Montaudon, François Laurent, Olivier Bar, Guillermo J. Tearney, Pierre Coste
Journal: JACC. Cardiovascular imaging (2020)

Among all patients presenting with myocardial infarction with nonobstructive coronary arteries (MINOCA), epicardial causes may be suspected when there is a correlation between electrocardiogram (ECG) changes and regional wall motion abnormalities (WMAs). We evaluated the diagnostic yield of intravascular optical coherence tomography (OCT) and cardiac magnetic resonance (CMR) in this specific setting.OCT is able to identify different morphologic features of coronary plaques that are well known causes of MINOCA. Furthermore, CMR has become the gold standard for detection of myocardial infarction in the setting of MINOCA.In a prospective 2-center study, consecutive patients with MINOCA including ECG features of ischemia associated with corresponding WMAs underwent OCT and CMR.Forty patients (mean age: 50 ± 11 years, 62.5% male, 32.5% with ST-segment elevation) were enrolled. Coronary arteries were normal on coronary angiography in 10 patients (25%); 18 patients (45%) presented minimal lumen irregularities, whereas the remaining 12 patients (30%) showed mild to moderate (≥30% but <50%) coronary lesions. Plaque rupture, eruptive calcific nodule, plaque erosion, lone thrombus, and spontaneous coronary artery dissection were found in 14 (35%), 1 (2.5%), 12 (30%), 3 (7.5%), and 2 (5%) patients, respectively. Acute myocardial infarction was evident at CMR in 31 of 40 patients (77.5%). Twenty-three patients (57.5%) had a substrate and/or diagnosis supported by both techniques with an evident relationship between the findings obtained by the 2 techniques. By coupling OCT with CMR, a substrate and/or diagnosis was found in 100% of cases.OCT coupled with CMR can provide a clear substrate and/or diagnosis in the vast majority of patients presenting with MINOCA including ECG features of ischemia associated with corresponding WMAs.
Scalp involvement in patients referred for patch testing: Retrospective cross-sectional analysis of North American Contact Dermatitis Group data, 1996 to 2016
Authors: Erin M. Warshaw, Sara A. Kullberg, Joel G. DeKoven, Howard I. Maibach, Donald V. Belsito, Jonathan I. Silverberg, Joseph F. Fowler, Amber R. Atwater, Denis Sasseville, Margo J. Reeder, James S. Taylor, Vincent A. DeLeo, Melanie D. Pratt, Kathryn A. Zug, Anthony F. Fransway
Journal: Journal of the American Academy of Dermatology (2020)
Glycolytic metabolism of pathogenic T cells enables early detection of GVHD by 13C-MRI
Authors: Julian C. Assmann, Don E. Farthing, Keita Saito, Natella Maglakelidze, Brittany Oliver, Kathrynne A. Warrick, Carole Sourbier, Christopher J. Ricketts, Thomas J. Meyer, Steven Z. Pavletic, W. Marston Linehan, Murali C. Krishna, Ronald E. Gress, Nataliya P. Buxbaum
Journal: Blood (2021)

Abstract Graft-versus-host disease (GVHD) is a prominent barrier to allogeneic hematopoietic stem cell transplantation (AHSCT). Definitive diagnosis of GVHD is invasive, and biopsies of involved tissues pose a high risk of bleeding and infection. T cells are central to GVHD pathogenesis, and our previous studies in a chronic GVHD mouse model showed that alloreactive CD4+ T cells traffic to the target organs ahead of overt symptoms. Because increased glycolysis is an early feature of T-cell activation, we hypothesized that in vivo metabolic imaging of glycolysis would allow noninvasive detection of liver GVHD as activated CD4+ T cells traffic into the organ. Indeed, hyperpolarized 13C-pyruvate magnetic resonance imaging detected high rates of conversion of pyruvate to lactate in the liver ahead of animals becoming symptomatic, but not during subsequent overt chronic GVHD. Concomitantly, CD4+ T effector memory cells, the predominant pathogenic CD4+ T-cell subset, were confirmed to be highly glycolytic by transcriptomic, protein, metabolite, and ex vivo metabolic activity analyses. Preliminary data from single-cell sequencing of circulating T cells in patients undergoing AHSCT also suggested that increased glycolysis may be a feature of incipient acute GVHD. Metabolic imaging is being increasingly used in the clinic and may be useful in the post-AHSCT setting for noninvasive early detection of GVHD.
Utility of minimally invasive measurement of hepatic venous pressure gradient via the peripheral antecubital vein
Authors: Akira Yamamoto, Norifumi Kawada, Atsushi Jogo, Kazuki Murai, Kohei Kotani, Ken Kageyama, Shinichi Hamamoto, Etsuji Sohgawa, Sawako Uchida-Kobayashi, Masaru Enomoto, Akihiro Tamori, Yukio Miki
Journal: Gut (2020)

We read with great interest the three articles by Bosch,1 Tripathi,2 and Monteiro.3 In those articles, measurement of hepatic venous pressure gradient (HVPG) played a key role in assessing the portal hypertension in patients with advanced liver disease. One obstacle to examining portal hypertension in clinical trials with suitably large cohorts is the substantial barrier to repeated measurement of HVPG. HVPG measurement is performed using a balloon catheter, most frequently inserted from the jugular vein. HVPG measurement is considered to require specific expertise and around a day of hospitalisation, making the procedure relatively expensive and burdensome.4 5 Despite many attempts, non-invasive methods have not yet been able to completely replace direct HVPG measurement.5 6 Here, we report a study on the methods for HVPG measurement from the peripheral antecubital vein (pHVPG). Although this method has been mentioned in a review of HVPG measurement, no detailed descriptions of this approach have been published.4

Forty-one measurements from 37 consecutive patients who …
Cerebrospinal fluid profile of NPTX2 supports role of Alzheimer’s disease-related inhibitory circuit dysfunction in adults with Down syndrome
Authors: Olivia Belbin, Mei-Fang Xiao, Desheng Xu, Maria Carmona-Iragui, Jordi Pegueroles, Bessy Benejam, Laura Videla, Susana Fernández, Isabel Barroeta, Raúl Nuñez-Llaves, Victor Montal, Eduard Vilaplana, Miren Altuna, Jordi Clarimón, Daniel Alcolea, Rafael Blesa, Alberto Lleó, Paul F. Worley, Juan Fortea
Journal: Molecular Neurodegeneration (2020)

Abstract Background Alzheimer’s disease (AD) is the major cause of death in adults with Down syndrome (DS). There is an urgent need for objective markers of AD in the DS population to improve early diagnosis and monitor disease progression. NPTX2 has recently emerged as a promising cerebrospinal fluid (CSF) biomarker of Alzheimer-related inhibitory circuit dysfunction in sporadic AD patients. The objective of this study was to evaluate NPTX2 in the CSF of adults with DS and to explore the relationship of NPTX2 to CSF levels of the PV interneuron receptor, GluA4, and existing AD biomarkers (CSF and neuroimaging). Methods This is a cross-sectional, retrospective study of adults with DS with asymptomatic AD (aDS, n = 49), prodromal AD (pDS, n = 18) and AD dementia (dDS, n = 27). Non-trisomic controls ( n = 34) and patients with sporadic AD dementia (sAD, n = 40) were included for comparison. We compared group differences in CSF NPTX2 according to clinical diagnosis and degree of intellectual disability. We determined the relationship of CSF NPTX2 levels to age, cognitive performance (CAMCOG, free and cued selective reminding, semantic verbal fluency), CSF levels of a PV-interneuron marker (GluA4) and core AD biomarkers; CSF Aβ 1–42 , CSF t-tau, cortical atrophy (magnetic resonance imaging) and glucose metabolism ([ 18 F]-fluorodeoxyglucose positron emission tomography). Results Compared to controls, mean CSF NPTX2 levels were lower in DS at all AD stages; aDS (0.6-fold, adj. p &lt; 0.0001), pDS (0.5-fold, adj. p &lt; 0.0001) and dDS (0.3-fold, adj. p &lt; 0.0001). This reduction was similar to that observed in sporadic AD (0.5-fold, adj. p &lt; 0.0001). CSF NPTX2 levels were not associated with age ( p = 0.6), intellectual disability ( p = 0.7) or cognitive performance (all p &gt; 0.07). Low CSF NPTX2 levels were associated with low GluA4 in all clinical groups; controls ( r 2 = 0.2, p = 0.003), adults with DS ( r 2 = 0.4, p &lt; 0.0001) and sporadic AD ( r 2 = 0.4, p &lt; 0.0001). In adults with DS, low CSF NPTX2 levels were associated with low CSF Aβ 1–42 ( r 2 &gt; 0.3, p &lt; 0.006), low CSF t-tau ( r 2 &gt; 0.3, p &lt; 0.001), increased cortical atrophy ( p &lt; 0.05) and reduced glucose metabolism ( p &lt; 0.05). Conclusions Low levels of CSF NPTX2, a protein implicated in inhibitory circuit function, is common to sporadic and genetic forms of AD. CSF NPTX2 represents a promising CSF surrogate marker of early AD-related changes in adults with DS.
Abstract 4115: QT Response to Exercise Maneuvers Predicts Genotype in Long QT Syndrome
Authors: Jorge Wong, Allan C Skanes, Raymond Yee, Lorne J Gula, George J Klein, Christopher Gray, Andrew D Krahn
Journal: Circulation (2008)

Genotyping of patients with suspected LQTS may influence prognosis and response to therapy. It remains expensive and difficult to access in many settings. The resting QT interval is normal or borderline in up to half of genetically affected patients, making expert directed genotyping important in the management of LQTS patients. We examined the use of provocative postural and exercise testing as a tool to diagnose LQTS and predict genotype. Patients with suspected LQTS based on a history of syncope or cardiac arrest, with an affected first-degree relative, or a borderline or prolonged QT interval underwent exercise testing. 117 genotyped patients underwent provocative testing consisting of resting supine and standing ECGs, and exercise testing using a modified Bruce protocol. ECGs were obtained during exercise and at 1-minute intervals during recovery. Medians and IQRs are presented, and compared with Wilcoxon scores. 57 Of the 117 patients had an LQT mutation (LQT+) identified by genetic testing (LQT1=29, LQT2=38). The resting and standing ECGs were most useful in discriminating LQT+ patients from LQT− patients, with a prolonged resting supine QTc that underwent exaggerated prolongation compared to unaffected family members (Table ). Genotype prediction in the LQT+ patients was best achieved using a combination of exercise QT and QTc changes that were most abnormal in LQT1 patients, along with hysteresis that was abnormal in LQT2 patients. Postural QTc changes are useful in identifying mutation positive LQTS patients. In patients with abnormal findings, LQT1 is associated with impaired QT and QTc shortening at peak exercise, and LQT2 patients have exaggerated hysteresis. Exercise testing is a useful simple tool in the diagnosis of LQTS that helps direct genetic testing.
68Ga-FAPI PET/CT in Assessment of Leptomeningeal Metastases in a Patient With Lung Adenocarcinoma
Authors: Bing Hao, Jingxun Wu, Yizhen Pang, Long Sun, Haojun Chen
Journal: Clinical Nuclear Medicine (2020)

Abstract We presented a case of 64-year-old woman with pathologically diagnosed lung adenocarcinoma. Brain metastases were highly suspected due to the appearance of neurological symptoms. However, no abnormal finding in the brain was observed on 18 F-FDG PET/CT. Contrast-enhanced MRI showed the presence of leptomeningeal metastases but with a negative cerebrospinal fluid analysis. For this reason, the patient underwent 68 Ga-FAPI PET/CT, later fused with MRI scans that showed intense uptake of 68 Ga-FAPI in leptomeningeal regions correspondent to the sites of gadolinium enhancement. This case highlights that 68 Ga-FAPI would be promising for the identification of leptomeningeal involvement in patients with malignant disease.