tbuckley/cabot-search huggingface dataset:
CXCR4 signaling controls dendritic cell location and activation at steady state and in inflammation
Authors: Carmen Gallego, Mathias Vétillard, Joseph Calmette, Mélanie Roriz, Viviana Marin-Esteban, Maximilien Evrard, Marie-Laure Aknin, Nicolas Pionnier, Manon Lefrançois, Françoise Mercier-Nomé, Yves Bertrand, Felipe Suarez, Jean Donadieu, Lai Guan Ng, Karl Balabanian, Françoise Bachelerie, Géraldine Schlecht-Louf
Journal: Blood (2021)
Human Hepatitis B Virus Negatively Impacts the Protective Immune Crosstalk Between Natural Killer and Dendritic Cells
Authors: Claudia De Pasquale, Stefania Campana, Chiara Barberi, Giacomo Sidoti Migliore, Daniela Oliveri, Marika Lanza, Cristina Musolino, Giovanni Raimondo, Soldano Ferrone, Teresa Pollicino, Guido Ferlazzo
Journal: Hepatology (2021)

Background and Aims Natural killer (NK) cells play a crucial role in the clearance of human viruses but their activity is significantly impaired in patients infected with chronic hepatitis B (CHB). Cooperation with dendritic cells (DCs) is pivotal for obtaining optimal NK cell antiviral function; thus, we investigated whether HBV might impact the ability of DCs to sustain NK cell functions. Approach and Results Human DCs were poor stimulators of interferon‐gamma (IFN‐γ) production by NK cells when exposed to HBV, while maintaining the capability to trigger NK cell cytotoxicity. HBV prevented DC maturation but did not affect their expression of human leukocyte antigen class I, thus allowing DCs to evade NK cell lysis. Tolerogenic features of DCs exposed to HBV were further supported by their increased expression of IL‐10 and the immunosuppressive enzyme indoleamine 2,3‐dioxygenase, which contributed to the impairment of DC‐mediated NK cell IFN‐γ production and proliferation, respectively. HBV could also inhibit the expression of inducible immunoproteasome (iP) subunits on DCs. In fact, NK cells could induce iP subunit expression on DCs, but they failed in the presence of HBV. Remarkably, circulating blood DC antigen1 (BDCA1) + DCs isolated from patients with CHB were functionally compromised, hence altering, in turn, NK cell responses. Conclusions The abnormal NK–DC interplay caused by HBV may significantly impair the efficacy of antiviral immune response in patients with CHB.
Topological data analysis reveals genotype–phenotype relationships in primary ciliary dyskinesia
Authors: Amelia Shoemark, Bruna Rubbo, Marie Legendre, Mahmoud R. Fassad, Eric G. Haarman, Sunayna Best, Irma C.M. Bon, Joost Brandsma, Pierre-Regis Burgel, Gunnar Carlsson, Siobhan B. Carr, Mary Carroll, Matt Edwards, Estelle Escudier, Isabelle Honoré, David Hunt, Gregory Jouvion, Michel R. Loebinger, Bernard Maitre, Deborah Morris-Rosendahl, Jean-Francois Papon, Camille M. Parsons, Mitali P. Patel, N. Simon Thomas, Guillaume Thouvenin, Woolf T. Walker, Robert Wilson, Claire Hogg, Hannah M. Mitchison, Jane S. Lucas
Journal: European Respiratory Journal (2021)

Primary ciliary dyskinesia (PCD) is a heterogeneous inherited disorder caused by mutations in approximately 50 cilia-related genes. PCD genotype-phenotype relationships have mostly arisen from small case series because existing statistical approaches to investigating relationships have been unsuitable for rare diseases.We applied a topological data analysis (TDA) approach to investigate genotype-phenotype relationships in PCD. Data from separate training and validation cohorts included 396 genetically defined individuals carrying pathogenic variants in PCD genes. To develop the TDA models, 12 clinical and diagnostic variables were included. TDA-driven hypotheses were subsequently tested using traditional statistics.Disease severity at diagnosis, measured by forced expiratory volume in 1 s (FEV1) z-score, was significantly worse in individuals with CCDC39 mutations (compared to other gene mutations) and better in those with DNAH11 mutations; the latter also reported less neonatal respiratory distress. Patients without neonatal respiratory distress had better preserved FEV1 at diagnosis. Individuals with DNAH5 mutations were phenotypically diverse. Cilia ultrastructure and beat pattern defects correlated closely to specific causative gene groups, confirming these tests can be used to support a genetic diagnosis.This large scale, multi-national study presents PCD as a syndrome with overlapping symptoms and variations in phenotype according to genotype. TDA modelling confirmed genotype-phenotype relationships reported by smaller studies (e.g. FEV1 worse with CCDC39 mutation) and identified new relationships, including FEV1 preservation with DNAH11 mutations and diversity of severity with DNAH5 mutations.
Radiation Therapy for Small-Cell Lung Cancer: ASCO Guideline Endorsement of an ASTRO Guideline
Authors: Megan E. Daly, Nofisat Ismaila, Roy H. Decker, Kristin Higgins, Dawn Owen, Ashish Saxena, Gregg E. Franklin, Dusty Donaldson, Bryan J. Schneider
Journal: Journal of Clinical Oncology (2021)

PURPOSE The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on radiation therapy (RT) for small-cell lung cancer (SCLC). Because of the relevance of this topic to ASCO membership, ASCO reviewed the guideline, applying a set of procedures and policies used to critically examine guidelines developed by other organizations. METHODS The ASTRO guideline on RT for SCLC was reviewed for developmental rigor by methodologists. Then, an ASCO Expert Panel reviewed the content and the recommendations. RESULTS The ASCO Expert Panel determined that the recommendations from ASTRO guideline on RT for SCLC, published in June 2020, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed ASTRO guideline on RT for SCLC with a few discussion points. RECOMMENDATIONS Recommendations addressed thoracic radiotherapy for limited-stage SCLC, role of stereotactic body radiotherapy in stage I or II node-negative SCLC, prophylactic cranial radiotherapy, and thoracic consolidation for extensive-stage SCLC. Additional information is available at www.asco.org/thoracic-cancer-guidelines .
Large-scale association analyses identify host factors influencing human gut microbiome composition
Authors: Alexander Kurilshikov, Carolina Medina-Gomez, Rodrigo Bacigalupe, Djawad Radjabzadeh, Jun Wang, Ayse Demirkan, Caroline I. Le Roy, Juan Antonio Raygoza Garay, Casey T. Finnicum, Xingrong Liu, Daria V. Zhernakova, Marc Jan Bonder, Tue H. Hansen, Fabian Frost, Malte C. Rühlemann, Williams Turpin, Jee-Young Moon, Han-Na Kim, Kreete Lüll, Elad Barkan, Shiraz A. Shah, Myriam Fornage, Joanna Szopinska-Tokov, Zachary D. Wallen, Dmitrii Borisevich, Lars Agreus, Anna Andreasson, Corinna Bang, Larbi Bedrani, Jordana T. Bell, Hans Bisgaard, Michael Boehnke, Dorret I. Boomsma, Robert D. Burk, Annique Claringbould, Kenneth Croitoru, Gareth E. Davies, Cornelia M. van Duijn, Liesbeth Duijts, Gwen Falony, Jingyuan Fu, Adriaan van der Graaf, Torben Hansen, Georg Homuth, David A. Hughes, Richard G. Ijzerman, Matthew A. Jackson, Vincent W. V. Jaddoe, Marie Joossens, Torben Jørgensen, Daniel Keszthelyi, Rob Knight, Markku Laakso, Matthias Laudes, Lenore J. Launer, Wolfgang Lieb, Aldons J. Lusis, Ad A. M. Masclee, Henriette A. Moll, Zlatan Mujagic, Qi Qibin, Daphna Rothschild, Hocheol Shin, Søren J. Sørensen, Claire J. Steves, Jonathan Thorsen, Nicholas J. Timpson, Raul Y. Tito, Sara Vieira-Silva, Uwe Völker, Henry Völzke, Urmo Võsa, Kaitlin H. Wade, Susanna Walter, Kyoko Watanabe, Stefan Weiss, Frank U. Weiss, Omer Weissbrod, Harm-Jan Westra, Gonneke Willemsen, Haydeh Payami, Daisy M. A. E. Jonkers, Alejandro Arias Vasquez, Eco J. C. de Geus, Katie A. Meyer, Jakob Stokholm, Eran Segal, Elin Org, Cisca Wijmenga, Hyung-Lae Kim, Robert C. Kaplan, Tim D. Spector, Andre G. Uitterlinden, Fernando Rivadeneira, Andre Franke, Markus M. Lerch, Lude Franke, Serena Sanna, Mauro D’Amato, Oluf Pedersen, Andrew D. Paterson, Robert Kraaij, Jeroen Raes, Alexandra Zhernakova
Journal: Nature Genetics (2021)
THU0087 Increased glucocorticoid beta mrna in peripheral blood mononuclear cells of rheumatoid arthritis patients
Authors: A Goecke, M Alamo, M Cuchacovich, C Sepulveda, H Gatica
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Rheumatoid Arthritis is an autoimmune inflammatory disease. A glucocorticoid resistance has been postulated as a factor involved in the pathogenesis of this disease.<sup>1</sup> The mechanisms involved in this GC-resistance has not been elucidated. Glucocorticoids´ effects are mediated trough an intracelular receptor, the glucocorticoid receptor (GCR). Thereare two isoforms of the GCR termed alpha and beta. The Beta isoform has recently been demostrated to act as a dominant negative inhibitor of the classic glucocorticoid receptor alpha.<sup>2</sup> As a potential <i>in vivo</i> inhibitor of GCR alpha activity, the expression of GCR beta isoform may be an important factor regulating target cell responsiveness to glucocorticoids. <h3>Objectives</h3> This study evaluated if there is an increase in GCR beta mRNA in peripheral blood mononuclear cells (PBMNC) from active newly diagnosed rheumatoid arthritis (RA) patients as compared to PBMNC from normal controls. <h3>Methods</h3> PBMNC were obtained from 9 active RA patients and 9 normal controls, matched by age and sex. A patient was defined as having an active disease if 3 of the following criteria were fulfilled: Erytrosedimentation rate &gt; 30 mm/hour, morning stiffness &gt; 1 h, &gt;6 tender joints, &gt; 3 swollen joints. The GCR alpha and beta were evaluated by semiquantitative RT-PCR. The RT-PCR products for both isoforms of glucocorticoid receptor were electrophoretically fractioned on 2% agarose gels stained with ethidium bromide. The intensity of ethdium bromude fluorescence was measured densitometrically and expressed as optical density units (ODU). The presence of statistically significant differences in ODU between groups was evaluated by the Wilcoxon test for matched pairs. <h3>Results</h3> RA patients presented a significant increase in the expression of GCR beta mRNA (median 571, range 208–968 ODU vs median 317, range 83–563 ODU in controls; P = 0.007) with no change in GCR alpha mRNA compared to controls. <h3>Conclusion</h3> RA patients present an increased expresion of the inhibitory beta isoform of the GCR in PBMNC. Glucocorticoids have well known anti-inflammatory properties, therefore an increased proportion of the inhibitory isoform of the glucocorticoid receptor could lead to a glucocorticoid-resistance status, wich could be a pathogenetic factor in RA by favouring the persistence of inflammatory processes. <h3>References</h3> Morand EF, Jefferiss M, Dixey J, Mitra D, Goulding NJ. Impaired glucocorticoid induction of mononuclear leucocyte lipocortin-1 in rheumatoid arthitis. Arthritis Rheum. 1994;37:207–11 Bamberger CM, Bamberger AM, de Castro M, Chrousos GP. Glucocorticoid receptor beta a potential endogenous inhibitor of glucocorticoid actions in humans. J Clin Invest. 1995;95:2435–41
Induction of Fetal Hemoglobin by Gene Therapy
Authors: Mark C. Walters
Journal: New England Journal of Medicine (2021)

Shortly after birth, fetal hemoglobin is replaced by adult hemoglobin in red cells, a process that reflects a developmental switch in the β-globin locus that favors the expression of β-globin and the suppression of γ-globin. Therapies that may abrogate this switch have long been pursued on the basis of observations that the persistence of fetal-hemoglobin production after birth mitigates the phenotypes of sickle cell disease and β-thalassemia major, as well as the absence of signs of either disease when fetal hemoglobin levels are high in utero or at birth.1,2 Pharmacologic inhibition of the globin developmental switch would require regular and . . .
THU0161 Rheumatoid arthritis with antikeratin antibodies (aka): a distinct immunogenetic or prognostic subgroup?
Authors: A Gómez, R Sanmartí, O Viñas, G Ercilla, JD Cañete, C Orellana, G Salvador, J Muñoz-Gómez
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Antikeratin antibodies (AKA) have been described as the most specific serologic markers of RA. However, whether these antibodies can identify a particular RA population it remains controversial. <h3>Objectives</h3> To compare the immunogenetic features (HLA-DRB1 and TNF-a polymorphism) and radiological severity of a group of patients with early RA, according to the presence or not of AKA. <h3>Methods</h3> 65 patients with early RA (48F/17M, mean age: 50 ± 14 y, mean disease duration 15 ± 12 mo, RF+:71%) were genotyped for HLA-DRB1 and TNF-a alleles. Hands and feet x-ray were taken at entry and then yearly during follow-up. The Larsen method was used to assess radiographic damage. AKA was determined by immunofluorescence using a modified Young method (sensitivity/specificity 60.2%/98.3%). <h3>Results</h3> AKA were present in the sera of 34 patients (prevalence of 52.3%). RF was more frequently found in AKA+ patients than in those without (85.3% vs. 54.8%; p = 0.007). No differences were observed according to the shared epitope and the frequency of HLA-DR4. The different TNF-a polymorphisms were equally distributed in AKA positive and negative populations. No significative radiological differences (presence of erosive disease and Larsen score) were observed at study entry between both populations. A trend to a more progressive radiological damage was observed at the end of follow-up.(32 ± 6 mo) in those patients with AKA, although the differences were no significative (Larsen score of 6.1 ± 4.3 in AKA(+) vs. 4.5 ± 5.5 in AKA (-). This trend is also observed when only RF positive patients were evaluated. <h3>Conclusion</h3> These results indicate that AKA cannot identify a distinct immunogenetic subgroup in Spanish reumatoid population. The role of AKA as a possible marker of a more aggressive joint disease merits further investigation.
C-Reactive Protein and the Vascular Endothelium: Implications for Plaque Instability⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Ishwarlal Jialal, Sridevi Devaraj, Uma Singh
Journal: Journal of the American College of Cardiology (2006)
High Court ruling on puberty blockers will worsen trans healthcare
Authors: Duncan McGregor, Callum Phillips
Journal: BMJ (2021)

We, the executive committee of GLADD (the Association of LGBTQ+ Doctors and Dentists), have profound concerns about the High Court’s judgment that children under 16 are unlikely to be competent to consent to the administration of puberty blockers.1 As a community of LGBTQ+ clinicians, we have personal and professional apprehension for the young trans people of this country.

Firstly, we are concerned for the safety and wellbeing of current young trans patients …
THU0213 The importance of screening and spinal instrumentation in patients with instability of upper cervical spine due to rheumatoid arthritis
Authors: Z Klezl, M Vesela, J Fousek, K Pavelka
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Instability of cervical spine is one of the most challenging fields in patients with rheumatoid arthritis (RA). Although most of the patients can be treated conservatively, some experience intractable pain with pronounced neurological symptoms. Sudden death has been reported in 10% of cases. <h3>Objectives</h3> Aim of this study was to determine the importance of screening of patients with RA and cervical spine instrumentation, which restores spinal stability before onset of cervical myelopathy. <h3>Methods</h3> We retrospectively evaluated 17 patients surgically treated for instability of the upper cervical spine during 1996 – 2001. Average age was 53.2 years (22 – 72), average duration of the disease was 14 years (3 – 24), 16 patients were women. There were 4 patients with cranial settling combined with atlanto-axial or/and subaxial instability and 13 with atlanto-axial instability; one of these patients had associated lateral atlanto-axial instability. Screening included electrophysiological examination, dynamic x-rays, in cases of significant instability MRI is performed in order to determine possible compression of the dural sac by pannus as described by Dvorak. The indications for surgery are: growing neurological deficit or pain, cranial settling, lateral subluxation of C1-C2 more than 2 mm and retrodental interval in patients with atlanto-axial subluxation 14 mm or less. Four different instrumentations were used, Ransford loop with sublaminar wires and cables, transarticular screws with wire loop, double sublaminar loop (Brooks) and Cervifix. All patients were using soft collar postoperatively, the one with Brooks procedure was placed into halo-vest for 6 weeks. <h3>Results</h3> Patients were evaluated using functional rating score and the Visual Analogue Scale with the mean follow up 14.3 months (6‑46). Marked improvement was found in both evaluations. Complications included cerebrospinal fluid leak, which required revision, delayed wound healing, injury to vertebral artery and delayed union of spinal fusion. Although they required longer hospital stay, they were not clinically significant. <h3>Conclusion</h3> Our results support the need for careful screening of patients with RA, which reveals instability associated with early neurological signs. Indication for surgery should be done before the onset of cervical myelopathy. Internal fixation with Cervifix, Ransford loop and transarticular fixation according to Magerl were satisfactory in maintaining stability of the upper cervical spine before healing of the fusion. Stability of the Brooks procedure was not satisfactory and therefore the patient had to be placed into halo-vest orthosis.
Self‐Assembly and Mechanical Properties of Engineered Protein Based Multifunctional Nanofiber for Accelerated Wound Healing
Authors: George Augustine, Mayilvahanan Aarthy, Hemalatha Thiagarajan, Sowmya Selvaraj, Numbi Ramdu Kamini, Ganesh Shanmugam, Niraikulam Ayyadurai
Journal: Advanced Healthcare Materials (2021)

The present work reports a new route for preparing tunable multifunctional biomaterials through the combination of synthetic biology and material chemistry. Genetically encoded catechol moiety is evolved in a nanofiber mat with defined surface and secondary reactive functional chemistry, which promotes self-assembly and wet adhesion property of the protein. The catechol moiety is further exploited for the controlled release of boric acid that provides a congenial cellular microenvironment for accelerated wound healing. The presence of 3,4-dihydroxyphenylalanine in the nanofiber mat act as a stimulus to trigger cell proliferation, migration, and vascularization to accelerate wound healing. Electron paramagnetic resonance, NMR, FTIR, and circular dichroism spectroscopy confirm the structural integrity, antioxidant property, and controlled release of boric acid. Fluorescent and scanning electron microscopy reveals the 3D architecture of nanofiber mat, which favors fibroblast growth, endothelial cell attachment, and tube formation, which are the desirable properties of a wound-healing material. Animal studies in the murine wound healing model assert that the multifunctional biomaterial significantly improve re-epithelialization and accelerate wound closure.
Diffusion-Weighted Imaging Reflects Tumor Grading and Microvascular Invasion in Hepatocellular Carcinoma
Authors: Alexey Surov, Maciej Pech, Jazan Omari, Frank Fischbach, Robert Damm, Katharina Fischbach, Maciej Powerski, Borna Relja, Andreas Wienke
Journal: Liver Cancer (2021)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; To date, there are inconsistent data about relationships between diffusion-weighted imaging (DWI) and tumor grading/microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Our purpose was to systematize the reported results regarding the role of DWI in prediction of tumor grading/MVI in HCC. &lt;b&gt;&lt;i&gt;Method:&lt;/i&gt;&lt;/b&gt; MEDLINE library, Scopus, and Embase data bases were screened up to December 2019. Overall, 29 studies with 2,715 tumors were included into the analysis. There were 20 studies regarding DWI and tumor grading, 8 studies about DWI and MVI, and 1 study investigated DWI, tumor grading, and MVI in HCC. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; In 21 studies (1,799 tumors), mean apparent diffusion coefficient (ADC) values (ADC&lt;sub&gt;mean&lt;/sub&gt;) were used for distinguishing HCCs. ADC&lt;sub&gt;mean&lt;/sub&gt; of G1–3 lesions overlapped significantly. In 4 studies (461 lesions), minimum ADC (ADC&lt;sub&gt;min&lt;/sub&gt;) was used. ADC&lt;sub&gt;min&lt;/sub&gt; values in G1/2 lesions were over 0.80 × 10&lt;sup&gt;−3&lt;/sup&gt; mm&lt;sup&gt;2&lt;/sup&gt;/s and in G3 tumors below 0.80 × 10&lt;sup&gt;−3&lt;/sup&gt; mm&lt;sup&gt;2&lt;/sup&gt;/s. In 4 studies (241 tumors), true diffusion (&lt;i&gt;D&lt;/i&gt;) was reported. A significant overlapping of &lt;i&gt;D&lt;/i&gt; values between G1, G2, and G3 groups was found. ADC&lt;sub&gt;mean&lt;/sub&gt; and MVI were analyzed in 9 studies (1,059 HCCs). ADC&lt;sub&gt;mean&lt;/sub&gt; values of MIV+/MVI− lesions overlapped significantly. ADC&lt;sub&gt;min&lt;/sub&gt; was used in 4 studies (672 lesions). ADC&lt;sub&gt;min&lt;/sub&gt; values of MVI+ tumors were in the area under 1.00 × 10&lt;sup&gt;−3&lt;/sup&gt; mm&lt;sup&gt;2&lt;/sup&gt;/s. In 3 studies (227 tumors), &lt;i&gt;D&lt;/i&gt; was used. Also, &lt;i&gt;D&lt;/i&gt; values of MVI+ lesions were predominantly in the area under 1.00 × 10&lt;sup&gt;−3&lt;/sup&gt; mm&lt;sup&gt;2&lt;/sup&gt;/s. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; ADC&lt;sub&gt;min&lt;/sub&gt; reflects tumor grading, and ADC&lt;sub&gt;min&lt;/sub&gt; and &lt;i&gt;D&lt;/i&gt; predict MVI in HCC. Therefore, these DWI parameters should be estimated for every HCC lesion for pretreatment tumor stratification. ADC&lt;sub&gt;mean&lt;/sub&gt; cannot predict tumor grading/MVI in HCC.
SARS-CoV-2 nucleocapsid protein and ultrastructural modifications in small bowel of a 4-week-negative COVID-19 patient
Authors: Roberta Rizzo, Luca Maria Neri, Carolina Simioni, Daria Bortolotti, Savino Occhionorelli, Giorgio Zauli, Paola Secchiero, Chiara Marina Semprini, Ilaria Laface, Juana Maria Sanz, Giovanni Lanza, Roberta Gafà, Angelina Passaro
Journal: Clinical Microbiology and Infection (2021)
What social media told us in the time of COVID-19: a scoping review
Authors: Shu-Feng Tsao, Helen Chen, Therese Tisseverasinghe, Yang Yang, Lianghua Li, Zahid A Butt
Journal: The Lancet Digital Health (2021)

With the onset of COVID-19 pandemic, social media has rapidly become a crucial communication tool for information generation, dissemination, and consumption. In this scoping review, we selected and examined peer-reviewed empirical studies relating to COVID-19 and social media during the first outbreak starting in November 2019 until May 2020. From an analysis of 81 studies, we identified five overarching public health themes concerning the role of online social platforms and COVID-19. These themes focused on: (i) surveying public attitudes, (ii) identifying infodemics, (iii) assessing mental health, (iv) detecting or predicting COVID-19 cases, (v) analyzing government responses to the pandemic, and (vi) evaluating quality of health information in prevention education videos. Furthermore, our review highlights the paucity of studies on the application of machine learning on social media data related to COVID-19 and a lack of studies documenting real-time surveillance developed with social media data on COVID-19. For COVID-19, social media can play a crucial role in disseminating health information as well as tackling infodemics and misinformation.