tbuckley/cabot-search huggingface dataset:
<i>Circ0008399</i> Interaction with WTAP Promotes Assembly and Activity of the m6A Methyltransferase Complex and Promotes Cisplatin Resistance in Bladder Cancer
Authors: Wenjie Wei, Jiayin Sun, Hui Zhang, Xingyuan Xiao, Chao Huang, Liang Wang, He Zhong, Yangkai Jiang, Xiaoping Zhang, Guosong Jiang
Journal: Cancer Research (2021)

Abstract Cisplatin (CDDP)-based chemotherapy is the first-line treatment for muscle-invasive and metastatic bladder cancer, yet most patients rapidly develop resistance. N6-methyladenosine (m6A) methylation is a pervasive RNA modification, and its specific role and potential mechanism in the regulation of CDDP chemosensitivity in bladder cancer remain unclear. Furthermore, studies have not yet fully elucidated whether circular RNA (circRNA) can directly regulate m6A modification of mRNA. Here we report upregulation of a novel circRNA, hsa_circ_0008399 (circ0008399), by eukaryotic translation initiation factor 4A3 (EIF4A3) in bladder cancer tissues and cell lines. Functionally, circ0008399 inhibited apoptosis of bladder cancer cells. Mechanistically, circ0008399 bound Wilms' tumor 1–associating protein (WTAP) to promote formation of the WTAP/METTL3/METTL14 m6A methyltransferase complex. Circ0008399 increased expression of TNF alpha-induced protein 3 (TNFAIP3) by increasing its mRNA stability in an m6A-dependent manner. In patients with bladder cancer, high expression of circ0008399 and WTAP was associated with poor outcomes. Importantly, activation of the circ0008399/WTAP/TNFAIP3 pathway decreased bladder cancer chemosensitivity to CDDP, and targeting the circ0008399/WTAP/TNFAIP3 axis enhanced the CDDP efficacy. Collectively, these findings give novel insights into circRNA-mediated regulation of m6A modifications and provide potential therapeutic targets for bladder cancer. Significance: A newly characterized circRNA circ0008399 binds WTAP to modulate expression of target RNA through m6A modification and reduce cisplatin sensitivity in bladder cancer, implicating the potential therapeutic value of targeting this axis.
Comparative Effectiveness of mRNA-based BNT162b2 Vaccine versus Adenovirus Vector–Based Ad26.COV2.S Vaccine for the Prevention of COVID-19 among Dialysis Patients
Authors: Steven M. Brunelli, Scott Sibbel, Steph Karpinski, Gilbert Marlowe, Adam G. Walker, Jeffrey Giullian, David Van Wyck, Tara Kelley, Rachael Lazar, Meredith L. Zywno, Jeffrey J. Connaire, Amy Young, Francesca Tentori
Journal: Journal of the American Society of Nephrology (2022)

Studies have demonstrated that mRNA-based SARS-CoV-2 vaccines are highly effective among patients on dialysis. Because individual vaccines may be differentially available or acceptable to patients, it is important to understand comparative effectiveness relative to other vaccines, such those on the basis of adenovirus technologies.In this retrospective study, we compared the clinical effectiveness of adenovirus vector-based Ad26.COV2.S (Janssen/Johnson & Johnson) to mRNA-based BNT162b2 (Pfizer/BioNTech) in a contemporary cohort of patients on dialysis. Patients who received a first BNT162b2 dose were matched 1:1 to Ad26.COV2.S recipients on the basis of date of first vaccine receipt, US state of residence, site of dialysis care (in-center versus home), history of COVID-19, and propensity score. The primary outcome was the comparative rate of COVID-19 diagnoses starting in the 7th week postvaccination. In a subset of consented patients who received Ad26.COV2.S, blood samples were collected ≥28 days after vaccination and anti-SARS-CoV-2 immunoglobulin G antibodies were measured.A total of 2572 matched pairs of patients qualified for analysis. Cumulative incidence rates of COVID-19 did not differ for BNT162b2 versus Ad26.COV2.S. No differences were observed in peri-COVID-19 hospitalizations and deaths among patients receiving BNT162b2 versus Ad26.COV2.S, who were diagnosed with COVID-19 during the at-risk period. Results were similar when excluding patients with a history of COVID-19, in subgroup analyses restricted to patients who completed the two-dose BNT162b2 regimen, and in patients receiving in-center hemodialysis. SARS-CoV-2 antibodies were detected in 59.4% of 244 patients who received Ad26.COV2.S.In a large real-world cohort of patients on dialysis, no difference was detected in clinical effectiveness of BNT162b2 and Ad26.COV2.S over the first 6 months postvaccination, despite an inconsistent antibody response to the latter.
Evolution of invasive meningococcal disease epidemiology in Europe, 2008 to 2017
Authors: Charles Nuttens, Jamie Findlow, Paul Balmer, David L Swerdlow, Myint Tin Tin Htar
Journal: Eurosurveillance (2022)

BackgroundInvasive meningococcal disease (IMD) epidemiology has fluctuated over the past 25 years and varies among serogroups, age groups and geographical locations.AimThis study analysed the evolution of European IMD epidemiology from 2008 to 2017 to identify trends.MethodsReported number of IMD cases and associated incidence were extracted from the European Centre for Disease Prevention and Control Surveillance Atlas for Infectious Diseases for individual European countries. Epidemiology and its evolution were analysed by serogroup and age group.ResultsOverall IMD incidence decreased by 34.4% between 2008 and 2017. Serogroup B remained predominant in 2017; despite a 56.1% decrease over the 10-year period, the rate of decrease has slowed in recent years and varies by age group. Serogroup C was the second most prevalent serogroup until 2016. Its incidence decreased among individuals aged 1-24 years, the main population targeted by MenC vaccination campaigns, but increases have occurred in other age groups. Incidences of serogroups W and Y were low but increased by > 500% and > 130% (to 0.10 and 0.07/100,000) respectively, from 2008 to 2017. Considering all serogroups, a marked modification of the evolution trends by age group has occurred, with increases in incidence mainly affecting older age groups.ConclusionAlthough the overall IMD incidence decreased in Europe between 2008 and 2017, increases were observed for serogroups W and Y, and in the older population when considering all serogroups. It may be necessary to adapt current vaccination strategies to reflect epidemiological changes and their likely future evolution.
68Ga-PSMA-11 and 18F-FDG PET/CT in a Case of Ductal Adenocarcinoma of the Prostate
Authors: Shuang Qiu, Aisheng Dong, Yan Zhu, Changjing Zuo
Journal: Clinical Nuclear Medicine (2022)

Prostatic ductal adenocarcinoma is an uncommon variant of prostatic carcinoma with aggressive behavior and worse prognosis. We describe 68 Ga-PSMA-11 and FDG PET/CT findings in a case of prostatic ductal adenocarcinoma with pelvic lymph node metastases. The majority of the prostate tumor and all the metastatic lesions showed no significant PSMA uptake but intense FDG uptake. The role of PSMA and FDG PET in the management of prostatic ductal adenocarcinoma needs to be investigated in a large number of patients.
Dynamics of the Upper Respiratory Tract Microbiota and Its Association with Mortality in COVID-19
Authors: Lili Ren, Yeming Wang, Jiaxin Zhong, Xia Li, Yan Xiao, Jie Li, Jing Yang, Guohui Fan, Li Guo, Zijie Shen, Lu Kang, Leisheng Shi, Qiong Li, Jizhou Li, Lin Di, Haibo Li, Conghui Wang, Ying Wang, Xinming Wang, Xiaohui Zou, Jian Rao, Li Zhang, Jianbin Wang, Yanyi Huang, Bin Cao, Jianwei Wang, Mingkun Li
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Alteration of human respiratory microbiota had been observed in coronavirus disease (COVID-19). How the microbiota is associated with the prognosis in COVID-19 is unclear. Objectives: To characterize the feature and dynamics of the respiratory microbiota and its associations with clinical features in patients with COVID-19. Methods: We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 patients with COVID-19 (including 39 deceased patients) and 95 healthy controls from the same geographic area. Meanwhile, the concentration of 27 cytokines and chemokines in plasma was measured for patients with COVID-19. Measurements and Main Results: The upper respiratory tract (URT) microbiota in patients with COVID-19 differed from that in healthy controls, whereas deceased patients possessed a more distinct microbiota, both on admission and before discharge/death. The alteration of URT microbiota showed a significant correlation with the concentration of proinflammatory cytokines and mortality. Specifically, Streptococcus-dominated microbiota was enriched in recovered patients, and showed high temporal stability and resistance against pathogens. In contrast, the microbiota in deceased patients was more susceptible to secondary infections and became more deviated from the norm after admission. Moreover, the abundance of S. parasanguinis on admission was significantly correlated with prognosis in nonsevere patients (lower vs. higher abundance, odds ratio, 7.80; 95% CI, 1.70-42.05). Conclusions: URT microbiota dysbiosis is a remarkable manifestation of COVID-19; its association with mortality suggests it may reflect the interplay between pathogens, symbionts, and the host immune status. Whether URT microbiota could be used as a biomarker for diagnosis and prognosis of respiratory diseases merits further investigation.
Diagnosis of liver fibrosis in ageing patients with HIV at risk for non-alcoholic fatty liver disease in Italy and Canada: assessment of a two-tier pathway
Authors: Giada Sebastiani, Jovana Milic, Claudia Gioe, Al Shaima Al Hinai, Adriana Cervo, Bertrand Lebouche, Marc Deschenes, Antonio Cascio, Giovanni Mazzola, Giovanni Guaraldi
Journal: The Lancet HIV (2022)
Abstract 11687: Management of Hypertrophic Obstructive Cardiomyopathy Using Septal Coiling
Authors: Antoine Addoumieh, Astrid J Serauto-Canache, Andrew D Badalamenti, Michael A Hust, Salman A Arain, Konstantinos Charitakis, Abhijeet Dhoble, Richard W Smalling
Journal: Circulation (2021)

Introduction: Hypertrophic obstructive cardiomyopathy (HOCM) is a genetic disorder associated with dynamic left ventricular outflow tract obstruction (LVOTO). Medical management of HOCM aims at decreasing the outflow tract gradient and improving symptoms. In a subset of patients, septal reduction is necessary to achieve symptomatic relief. Alcohol Septal Ablation (ASA) is an accepted method for septal reduction, though it carries risks of complications including unpredictable ethanol diffusion, complete heart block requiring pacemaker and death. We sought to evaluate septal coil embolization (CE) as another method to achieve hemodynamic improvement in HOCM patients with severe LVOTO. Method: We identified 53 HOCM patients that underwent CE at our institution. Baseline septal thickness and LVOT gradients were measured at rest and with Valsalva during echocardiogram (ECHO) and catheterization. Immediate and 2-6 month follow-up post coiling gradients were measured using both modalities and results were compared to baseline. Septal thickness was compared before and after CE. Paired t-test was used to compare pre and post values. Results: Mean age was 68, range (31-90) years, 60% were females, 5.6% had prior permanent pacemaker (PPM). Invasive mean gradient (MG) at rest was 56.6 mmHg and immediately post CE was 16.5 mmHg with mean difference (MD) of 40 mmHg (95% CI 10.6-22.4) (p&lt;0.01). Invasive MG following PVC was 123 mmHg pre and 34 mmHg post with MD of 79 mmHg (95% CI 65-111) (p&lt;0.01). ECHO MG at rest was 79 mmHg and 35 mmHg on follow up with MD 44 mmHg (95% CI 27-60) (p&lt;0.01). Septal thickness at baseline was 17.4 mm and was 14.6 mm on follow up with average reduction of 2.8 mm (95% CI 1.5-4.1) (p&lt;0.01). Ninety three percent of patients reported class III-IV NYHA symptoms at baseline, compared to 14% on follow up. A total of 4 patients required new PPM placement and 6 patients required recoiling. Conclusion: Our study demonstrated a safe and effective alternative compared to ASA for treatment of severely symptomatic HOCM patients. The use of coils compared to alcohol ablation for septal reduction affords more precise tissue ablation with a concomitant reduction in the need for permanent pacemaker insertion with a similar hemodynamic and symptomatic success rate.
Long-term safety and efficacy of dupilumab in patients with moderate-to-severe asthma (TRAVERSE): an open-label extension study
Authors: Michael E Wechsler, Linda B Ford, Jorge F Maspero, Ian D Pavord, Alberto Papi, Arnaud Bourdin, Henrik Watz, Mario Castro, Natalia M Nenasheva, Yuji Tohda, David Langton, Guido Cardona, Christian Domingo, Hae Sim Park, Kenneth R Chapman, Xuezhou Mao, Yi Zhang, Asif H Khan, Yamo Deniz, Paul J Rowe, Upender Kapoor, Faisal A Khokhar, Leda P Mannent, Marcella Ruddy, Elizabeth Laws, Nikhil Amin, Megan Hardin
Journal: The Lancet Respiratory Medicine (2021)
Estimating total spending by source of funding on routine and supplementary immunisation activities in low-income and middle-income countries, 2000–17: a financial modelling study
Authors: Gloria Ikilezi, Angela E Micah, Steven D Bachmeier, Ian E Cogswell, Emilie R Maddison, Hayley N Stutzman, Golsum Tsakalos, Logan Brenzel, Joseph L Dieleman
Journal: The Lancet (2021)

Childhood immunisation is one of the most cost-effective health interventions. However, despite its known value, global access to vaccines remains far from complete. Although supply-side constraints lead to inadequate vaccine coverage in many health systems, there is no comprehensive analysis of the funding for immunisation. We aimed to fill this gap by generating estimates of funding for immunisation disaggregated by the source of funding and the type of activities in order to highlight the funding landscape for immunisation and inform policy making.
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine through 6 Months
Authors: Stephen J Thomas, Edson D Moreira, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, Stephen Lockhart, John L Perez, Gonzalo Pérez Marc, Fernando P Polack, Cristiano Zerbini, Ruth Bailey, Kena A Swanson, Xia Xu, Satrajit Roychoudhury, Kenneth Koury, Salim Bouguermouh, Warren V Kalina, David Cooper, Robert W Frenck, Laura L Hammitt, Özlem Türeci, Haylene Nell, Axel Schaefer, Serhat Ünal, Qi Yang, Paul Liberator, Dina B Tresnan, Susan Mather, Philip R Dormitzer, Uğur Şahin, William C Gruber, Kathrin U Jansen
Journal: New England Journal of Medicine (2021)

BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) full-length spike protein. BNT162b2 is highly efficacious against coronavirus disease 2019 (Covid-19) and is currently approved, conditionally approved, or authorized for emergency use worldwide. At the time of initial authorization, data beyond 2 months after vaccination were unavailable.In an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy trial, we randomly assigned 44,165 participants 16 years of age or older and 2264 participants 12 to 15 years of age to receive two 30-μg doses, at 21 days apart, of BNT162b2 or placebo. The trial end points were vaccine efficacy against laboratory-confirmed Covid-19 and safety, which were both evaluated through 6 months after vaccination.BNT162b2 continued to be safe and have an acceptable adverse-event profile. Few participants had adverse events leading to withdrawal from the trial. Vaccine efficacy against Covid-19 was 91.3% (95% confidence interval [CI], 89.0 to 93.2) through 6 months of follow-up among the participants without evidence of previous SARS-CoV-2 infection who could be evaluated. There was a gradual decline in vaccine efficacy. Vaccine efficacy of 86 to 100% was seen across countries and in populations with diverse ages, sexes, race or ethnic groups, and risk factors for Covid-19 among participants without evidence of previous infection with SARS-CoV-2. Vaccine efficacy against severe disease was 96.7% (95% CI, 80.3 to 99.9). In South Africa, where the SARS-CoV-2 variant of concern B.1.351 (or beta) was predominant, a vaccine efficacy of 100% (95% CI, 53.5 to 100) was observed.Through 6 months of follow-up and despite a gradual decline in vaccine efficacy, BNT162b2 had a favorable safety profile and was highly efficacious in preventing Covid-19. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.).
Siglec-F–expressing neutrophils are essential for creating a profibrotic microenvironment in renal fibrosis
Authors: Seungwon Ryu, Jae Woo Shin, Soie Kwon, Jiwon Lee, Yong Chul Kim, Yoe-Sik Bae, Yong-Soo Bae, Dong Ki Kim, Yon Su Kim, Seung Hee Yang, Hye Young Kim
Journal: Journal of Clinical Investigation (2022)

The roles of neutrophils in renal inflammation are currently unclear. On examining these cells in the unilateral ureteral obstruction murine model of chronic kidney disease, we found that the injured kidney bore a large and rapidly expanding population of neutrophils that expressed the eosinophil marker Siglec-F. We first verified that these cells were neutrophils. Siglec-F+ neutrophils were recently detected in several studies in other disease contexts. We then showed that a) these cells were derived from conventional neutrophils in the renal vasculature by TGF-β1 and GM-CSF; b) they differed from their parent cells by more frequent hypersegmentation, higher expression of profibrotic inflammatory cytokines, and notably, expression of collagen 1; and c) their depletion reduced collagen deposition and disease progression, but adoptive transfer increased renal fibrosis. These findings have thus unveiled a subtype of neutrophils that participate in renal fibrosis and a potentially new therapeutic target in chronic kidney disease.
α-Parvin Defines a Specific Integrin Adhesome to Maintain the Glomerular Filtration Barrier
Authors: Manuel Rogg, Jasmin I. Maier, Clara Van Wymersch, Martin Helmstädter, Alena Sammarco, Maja Lindenmeyer, Paulina Zareba, Eloi Montanez, Gerd Walz, Martin Werner, Nicole Endlich, Thomas Benzing, Tobias B. Huber, Christoph Schell
Journal: Journal of the American Society of Nephrology (2022)

The cell-matrix adhesion between podocytes and the glomerular basement membrane is essential for the integrity of the kidney's filtration barrier. Despite increasing knowledge about the complexity of integrin adhesion complexes, an understanding of the regulation of these protein complexes in glomerular disease remains elusive.We mapped the in vivo composition of the podocyte integrin adhesome. In addition, we analyzed conditional knockout mice targeting a gene (Parva) that encodes an actin-binding protein (α-parvin), and murine disease models. To evaluate podocytes in vivo, we used super-resolution microscopy, electron microscopy, multiplex immunofluorescence microscopy, and RNA sequencing. We performed functional analysis of CRISPR/Cas9-generated PARVA single knockout podocytes and PARVA and PARVB double knockout podocytes in three- and two-dimensional cultures using specific extracellular matrix ligands and micropatterns.We found that PARVA is essential to prevent podocyte foot process effacement, detachment from the glomerular basement membrane, and the development of FSGS. Through the use of in vitro and in vivo models, we identified an inherent PARVB-dependent compensatory module at podocyte integrin adhesion complexes, sustaining efficient mechanical linkage at the filtration barrier. Sequential genetic deletion of PARVA and PARVB induces a switch in structure and composition of integrin adhesion complexes. This redistribution of these complexes translates into a loss of the ventral actin cytoskeleton, decreased adhesion capacity, impaired mechanical resistance, and dysfunctional extracellular matrix assembly.The findings reveal adaptive mechanisms of podocyte integrin adhesion complexes, providing a conceptual framework for therapeutic strategies to prevent podocyte detachment in glomerular disease.
Single-Cell Chromatin and Gene-Regulatory Dynamics of Mouse Nephron Progenitors
Authors: Sylvia Hilliard, Giovane Tortelote, Hongbing Liu, Chao-Hui Chen, Samir S. El-Dahr
Journal: Journal of the American Society of Nephrology (2022)

We reasoned that unraveling the dynamic changes in accessibility of genomic regulatory elements and gene expression at single-cell resolution will inform the basic mechanisms of nephrogenesis.
29P Brigatinib (BRG) vs crizotinib (CRZ) in anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor-naive ALK+ non-small cell lung cancer (NSCLC): ALTA-1L final results
Authors: M. Tiseo, S. Popat, H.R. Kim, M-J. Ahn, J.C. Yang, J-Y. Han, M.J. Hochmair, K.H. Lee, A. Delmonte, M.R. Garcia Campelo, D-W. Kim, F. Griesinger, E. Felip, R. Califano, A.I. Spira, S.N. Gettinger, H.M. Lin, Y. Liu, F. Vranceanu, D.R. Camidge
Journal: Annals of Oncology (2022)
189P Assessment of seroconversion after SARS-CoV2 vaccination in patients with lung cancer
Authors: I.P. Trontzas, I. Vathiotis, G. Gomatou, M. Grammoustianou, I. Tsamis, M. Anagnostakis, V. Sakka, G. Poulakou, K.N. Syrigos, E.A. Kotteas
Journal: Annals of Oncology (2022)
Rare Case of Small Cell Metastatic Prostatic Adenocarcinoma, Properly Staged by 68Ga-PSMA PET/CT Scan
Authors: Zahra Bakhshi Golestani, Salman Soltani, Mahmoud Reza Kalantari, Hamid Reza Ghorbani, Atena Aghaee
Journal: Clinical Nuclear Medicine (2022)

Abstract Small cell carcinoma (SCC) of the prostate is a very rare entity and one of most aggressive neuroendocrine malignancies of prostate. We present a 60-year-old man with pathology-proven prostatic SCC by transrectal biopsy with ultrasonography guidance and Gleason score of 5 + 5. He was referred to perform 68 Ga-PSMA PET/CT scan for staging. The scan showed PSMA uptake in the prostate bed and multiple large pelvic lymph nodes. As we know, 68 Ga-PSMA uptake in the de novo form of SCC of prostate is not commonly found in the literature.
Use of a Bougie vs Endotracheal Tube With Stylet and Successful Intubation on the First Attempt Among Critically Ill Patients Undergoing Tracheal Intubation
Authors: Michael J. Brenner, Brendan A. McGrath, Tim M. Cook
Journal: JAMA (2022)

To the Editor A recent randomized trial1 comparing success rates in tracheal intubation with bougie vs endotracheal tube with stylet found no difference in outcomes. This negative result raises several questions about which other measures might be helpful when intubating critically ill patients.