tbuckley/cabot-search huggingface dataset:
A randomized controlled trial concerning Antimicrobial Prophylaxis (AMP) in Transurethral Resection of Bladder tumor (TURB): Another step forward in antimicrobial stewardship?
Authors: E. Baten, F. Van Der Aa, H. Goethuys, K. Slabbaert, I. Arijs, K. Van Renterghem
Journal: European Urology (2021)
The ‘Peptide for Life’ Initiative: a call for action to provide equal access to the use of natriuretic peptides in the diagnosis of acute heart failure across <scp>Europe</scp>
Authors: Antoni Bayes‐Genis, James L. Januzzi, A. Mark Richards, Henrike Arfsten, Rudolf A. de Boer, Michele Emdin, Arantxa González, Tiny Jaarsma, Pardeep S. Jhund, Christian Mueller, Julio Núñez, Patrick Rossignol, Ivan Milinkovic, Giuseppe M.C. Rosano, Andrew Coats, Petar Seferovic
Journal: European Journal of Heart Failure (2021)
Abstract 16547: Preserved Ejection Fraction With Low Gradient and Low Flow Aortic Stenosis: A True Entity or Misclassification? Can Left Ventricular Remodeling Differences Improve Characterization of This Group?
Authors: Praveen Mehrotra, Katrijn Jansen, Michael Picard, Judy Hung
Journal: Circulation (2011)

Background: There is uncertainty in defining patients (pts) with preserved ejection fraction (EF) and low gradient, low flow severe aortic stenosis (PLGF AS). Studies propose that PLGF AS pts have ...
Chuna Manual Therapy vs Usual Care for Patients With Nonspecific Chronic Neck Pain
Authors: Jinho Lee, Jae-Heung Cho, Koh-Woon Kim, Jun-Hwan Lee, Me-riong Kim, Joowon Kim, Min-Young Kim, Hyun-Woo Cho, Yoon Jae Lee, Sook-Hyun Lee, Joon-Shik Shin, Lawrence L. Prokop, Byung-Cheul Shin, In-Hyuk Ha
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The incidence rate of neck pain is increasing worldwide, and the disease is associated with a high social burden. Manual therapy has been widely applied in the treatment of neck pain, but a high-quality, pragmatic randomized clinical trial for this treatment has not been conducted to date. <h3>Objective</h3> This study aimed to compare the effectiveness of Chuna manual therapy with that of usual care for patients with chronic neck pain. <h3>Design, Setting, and Participants</h3> A multicenter, assessor-blinded, pragmatic, randomized clinical trial was conducted between October 18, 2017, and June 28, 2019. This intention-to-treat analysis included 108 patients with chronic neck pain persisting for at least 3 months; patients were recruited from 5 hospitals in Korea. <h3>Interventions</h3> Ten sessions (2 sessions per week for 5 weeks) of Chuna manual therapy or usual care (electrotherapy and oral medication) were conducted. <h3>Main Outcomes and Measures</h3> The main outcome was the difference in visual analog scale (VAS) score for chronic neck pain between baseline and 5 weeks after randomization. <h3>Results</h3> This randomized clinical trial recruited 108 patients (mean [SD] age, 38.4 [9.3] years; 73 women [67.6%]). Fifty-four patients were allocated to the Chuna therapy group, and 54 received usual care. At 5 weeks after randomization, manual therapy showed statistically superior results compared with usual care in terms of pain (difference in chronic neck pain VAS, 16.8 mm; 95% CI, 10.1-23.5 mm), function (difference in Neck Disability Index, 8.6%; 95% CI, 4.2%-13.1%), and quality of life (difference in the European Quality of Life–5 Dimension 5 Levels (EQ-5D-5L) scores, −0.07 points; 95% CI, −0.11 to −0.02 points). Regarding the 1-year cumulative values measured using area under the curve analyses, superior outcomes were attained in the manual therapy group in terms of the numerical rating scale for chronic neck pain (1.3 points; 95% CI, 0.5-2.0 points), Neck Disability Index (6.7%; 95% CI, 2.5%-10.9%), Neck Pain Questionnaire (7.4%; 95% CI, 2.3%-12.6%), and EQ-5D-5L scores (−0.03 points; −0.07 to 0.00 points). <h3>Conclusions and Relevance</h3> In this randomized clinical trial, for patients with chronic neck pain, Chuna manual therapy was more effective than usual care in terms of pain and functional recovery at 5 weeks and 1 year after randomization. These results support the need to consider recommending manual therapies as primary care treatments for chronic neck pain. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT03294785
Utility of Phosphate Binder Equivalent Dose Concept
Authors: Manjunath Kulkarni
Journal: Journal of the American Society of Nephrology (2021)

We read with interest the AMPLIFY trial.1 The authors must be commended for selection of study participants that reflected real-world difficulties in managing elevated phosphorus levels. The study participants were treated with different phosphate binders such as Sevelamer, Lanthanum Carbonate, Sucroferric Oxyhydroxide, and calcium-based phosphate binders. The phosphate binders received by the patients were not balanced in both arms of the trial. Stratification was done on the basis of sevelamer and nonsevelamer phosphate binders. However, not all nonsevelamer-based binders are equal in their phosphate binding capacity. For example, in Supplemental Table 2, 14.3% in the placebo plus binder group were on sucroferric oxyhydroxide (SFOH) as compared with 4.3% in the Tenapanor plus binder group. SFOH is a potent phosphate binder, and it cannot be compared with other binders. Each gram of SFOH binds to approximately 260 mg of phosphorous in the gut compared with 1 g of sevelamer that binds to 21 mg of phosphorous.2 Using the concept of phosphate binder equivalent dose (PBED) would have simplified comparison of phosphate binders.3 This would give a clear picture of how much phosphate binder each trial arm received. Although it may not be possible to quantify exact amounts of phosphate bound by phosphate binders, the relative phosphate-binding capacity of various binders can be a useful tool for comparing therapy when doses of multiple phosphate binders are given to patients.
Abstract SY16-02: Using patient-derived models for functional precision oncology in advanced breast cancer
Authors: Alana L. Welm
Journal: Cancer Research (2021)

Abstract Patient derived xenografts (PDX) are valuable, clinically-relevant models of cancer. Their close genomic, phenotypic, and temporal association with patient tumors makes them well-suited for pre-clinical and co-clinical studies that assess the potential of new therapeutics. However, PDX models are not amenable to large-scale drug sensitivity studies or real-time precision oncology due to their relatively slow growth, high cost, and low throughput. To address this, we established and characterized organoid lines from breast cancer patient tumors and PDXs and evaluated their fidelity to the original tumors and their utility in high-throughput therapeutic studies. Results of comparisons between in vitro and in vivo patient-derived models of breast cancer will be presented, along with extension of this technology to inform patient care in an IRB-approved study of precision oncology. Our work demonstrates that breast cancer organoid models are a powerful parallel resource to PDX models, especially useful for efficient determination of drug responses, and are amenable to informing real-time patient care in a functional precision oncology setting. Citation Format: Alana L. Welm. Using patient-derived models for functional precision oncology in advanced breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY16-02.
Video endoscopic inguinal lymphadenectomy: Step-by-step technique and mid-term oncological outcomes
Authors: J.M. Gaya Sopena, A. Rosales, A. Gallioli, P. Diana, P. Gavrilov, A. Territo, A. Piana, A. Sánchez-Puy, J.F. Calderón, H. Vila-Reyes, J. Palou, A. Breda
Journal: European Urology (2021)
Targeted-lung delivery of dexamethasone using gated mesoporous silica nanoparticles. A new therapeutic approach for acute lung injury treatment
Authors: Alba García-Fernández, Mónica Sancho, Viviana Bisbal, Pedro Amorós, María D. Marcos, Mar Orzáez, Félix Sancenón, Ramón Martínez-Máñez
Journal: Journal of Controlled Release (2021)
Partha Kar: Let’s avoid the trap of division
Authors: Partha Kar
Journal: BMJ (2021)

Last month an outcry erupted over comments by Dido Harding, former head of Test and Trace, who has applied to succeed Simon Stevens as chief executive of NHS England. Harding was quoted in a Sunday Times story about her pitch for the role, headlined “Dido Harding: Make NHS less reliant on foreigners.”

Gabriel Pogrund, the paper’s Whitehall correspondent, wrote: “Baroness Harding of Winscombe has vowed to end England’s reliance on foreign doctors and nurses if she becomes the next head of the NHS . . . Harding, 53, would challenge the ‘prevailing orthodoxy’ in government that it is better to import medical professionals from overseas and benefit from the investment of other countries because of the huge cost of training a doctor.”

Putting aside the …
ダウン症候群の小児における骨髄性前白血病の形質転換骨髄性白血病への進行のメカニズム【JST・京大機械翻訳】
Authors: Labuhn Maurice, Perkins Kelly, Matzk Soren, Varghese Leila, Garnett Catherine, Papaemmanuil Elli, Metzner Marlen, Kennedy Alison, Amstislavskiy Vyacheslav, Risch Thomas, Bhayadia Raj, Samulowski David, Hernandez David Cruz, Stoilova Bilyana, Iotchkova Valentina, Oppermann Udo, Scheer Carina, Yoshida Kenichi, Schwarzer Adrian, Taub Jeffrey, D Crispino John, J Weiss Mitchell, Hayashi Asuhide, Taga Takashi, Ito Etsuro, Ogawa Seishi, Reinhardt Dirk, Yaspo Marie-Laure, J Campbell Peter, Roberts Irene, Constantinescu Stefan, Vyas Paresh, Heckl Dirk, Klusmann Jan-Henning
Journal: Cancer Cell (2019)
The commensal bacterium <i>Lactiplantibacillus plantarum</i> imprints innate memory-like responses in mononuclear phagocytes
Authors: Aize Pellon, Diego Barriales, Ainize Peña-Cearra, Janire Castelo-Careaga, Ainhoa Palacios, Nerea Lopez, Estibaliz Atondo, Miguel Angel Pascual-Itoiz, Itziar Martín-Ruiz, Leticia Sampedro, Monika Gonzalez-Lopez, Laura Bárcena, Teresa Martín-Mateos, Jose María Landete, Rafael Prados-Rosales, Laura Plaza-Vinuesa, Rosario Muñoz, Blanca de las Rivas, Juan Miguel Rodríguez, Edurne Berra, Ana M. Aransay, Leticia Abecia, Jose Luis Lavín, Hector Rodríguez, Juan Anguita
Journal: Gut Microbes (2021)

Gut microbiota is a constant source of antigens and stimuli to which the resident immune system has developed tolerance. However, the mechanisms by which mononuclear phagocytes, specifically monocytes/macrophages, cope with these usually pro-inflammatory signals are poorly understood. Here, we show that innate immune memory promotes anti-inflammatory homeostasis, using as model strains of the commensal bacterium Lactiplantibacillus plantarum. Priming of monocytes/macrophages with bacteria, especially in its live form, enhances bacterial intracellular survival and decreases the release of pro-inflammatory signals to the environment, with lower production of TNF and higher levels of IL-10. Analysis of the transcriptomic landscape of these cells shows downregulation of pathways associated with the production of reactive oxygen species (ROS) and the release of cytokines, chemokines and antimicrobial peptides. Indeed, the induction of ROS prevents memory-induced bacterial survival. In addition, there is a dysregulation in gene expression of several metabolic pathways leading to decreased glycolytic and respiratory rates in memory cells. These data support commensal microbe-specific metabolic changes in innate immune memory cells that might contribute to homeostasis in the gut.
Author Correction: Postprandial glycaemic dips predict appetite and energy intake in healthy individuals
Authors: Patrick Wyatt, Sarah E. Berry, Graham Finlayson, Ruairi O’Driscoll, George Hadjigeorgiou, David A. Drew, Haya Al Khatib, Long H. Nguyen, Inbar Linenberg, Andrew T. Chan, Tim D. Spector, Paul W. Franks, Jonathan Wolf, John Blundell, Ana M. Valdes
Journal: Nature Metabolism (2021)
Abstract 2706: Utilizing RNAscope to assess STK11-LoF-dependent transcriptional phenotypes in human NSCLC biopsies and evaluate its potential to predict anti-PD1 therapy response
Authors: Hailey M. Sarausky, Sean M. Lenahan, David Joseph Seward
Journal: Cancer Research (2021)

Abstract Our work demonstrates RNAscope allows simultaneous quantitative assessment of multiple transcripts in situ using formalin fixed paraffin embedded (FFPE) human non-small cell lung cancer (NSCLC) biopsies and suggests this methodology could be used as a rapid surrogate biomarker for genotype/transcriptome profiling stemming for Serine Threonine Kinase 11 (STK11) loss of function (LoF). Recent clinical studies have correlated anti-PD1 therapy resistance in NSCLC with somatic disruption of STK11. Historically, rapid assessment of STK11 status using immunohistochemistry (IHC) has been a challenge. Our work in human NSCLC cell lines suggests that STK11 loss correlates with changes in tumor intrinsic cytokine expression. Several recent studies have suggested such changes may drive immune evasion. We therefore wondered whether cytokine expression profiles from primary human NSCLC biopsies might be used as a reliable biomarker to predict anti-PD1 therapy response. Here we present our findings using multiplexed RNAscope probes on KRAS-driven primary human NSCLC biopsies with and without STK11 loss. This initial work focuses on cytokines identified using our cell culture models as a proof of principle approach. Using CRISPR-Cas9 we engineered paired STK11 KO cell lines derived from 3 independent KRAS-driven human lung adenocarcinomas (NCI-H441, NCI-H1792, NCI-H2009). RNAseq and differential gene expression analysis revealed STK11-loss-dependent increases in IL-6, IL-8 and IL-32 in all three lines. We then created FFPE cell blocks using these cell lines and validated the RNAseq expression changes with multiplexed RNAscope probes in situ. Next, we informatically searched the molecular pathology archives at the UVM medical center and identified primary KRAS-driven human NSCLC biopsies with and without predicted STK11 loss. We then performed multiplexed RNAscope analysis on these samples to quantify IL-6, IL-8 and IL-32 gene expression as a function of tumor genotype in vivo. Our data suggest RNAscope represents a valid methodology to exploit quantitative differential gene expression as a reliable and reproducible surrogate biomarker of somatic STK11 disruption in NSCLC. Our future studies aim to establish whether genotype-dependent cytokine profiles predict anti-PD1 therapy response in KRAS-driven lung adenocarcinomas. Citation Format: Hailey M. Sarausky, Sean M. Lenahan, David Joseph Seward. Utilizing RNAscope to assess STK11-LoF-dependent transcriptional phenotypes in human NSCLC biopsies and evaluate its potential to predict anti-PD1 therapy response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2706.
Prospective nationwide multicentre cohort study of the clinical significance of autoimmune features in idiopathic interstitial pneumonias
Authors: Noriyuki Enomoto, Sakae Homma, Naohiko Inase, Yasuhiro Kondoh, Takeshi Saraya, Hajime Takizawa, Yoshikazu Inoue, Hiroshi Ishii, Yoshio Taguchi, Shinyu Izumi, Yasuhiko Yamano, Yoshinori Tanino, Yasuhiko Nishioka, Mikio Toyoshima, Koshi Yokomura, Shiro Imokawa, Naoki Koshimizu, Takehisa Sano, Taisuke Akamatsu, Hiroshi Mukae, Motoyasu Kato, Naoki Hamada, Hirofumi Chiba, Shinobu Akagawa, Shigeo Muro, Hironori Uruga, Hiroyuki Matsuda, Yusuke Kaida, Miho Kanai, Kazutaka Mori, Masafumi Masuda, Hironao Hozumi, Tomoyuki Fujisawa, Yutaro Nakamura, Noriyoshi Ogawa, Takafumi Suda
Journal: Thorax (2021)

Some patients with idiopathic interstitial pneumonia (IIP) show autoimmune features. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept in these patients. However, retrospective studies reported conflicting results of its prognosis. Therefore, this study was conducted to prospectively evaluate the clinical significance of autoimmune features in patients with IIP.This nationwide multicentre study prospectively enrolled consecutive patients with IIP. At the diagnosis, we systematically evaluated 63 features suggestive of connective tissue diseases using a checklist including symptoms/signs and autoantibodies, which contained most items of the IPAF criteria and followed up with the patients. Clinical phenotypes were included in a cluster analysis.In 376 patients with IIP enrolled, 70 patients (18.6%) met the IPAF criteria. The proportion of patients with IPAF was significantly lower in idiopathic pulmonary fibrosis (IPF) than in non-IPF (6.0% vs 24.3%, respectively). During a median observation period of 35 months, patients with IPAF more frequently developed systemic autoimmune diseases and had less frequent acute exacerbation of IIPs than patients with non-IPAF. IPAF diagnosis was significantly associated with better survival and was an independent positive prognostic factor in total and patients with non-IPF. Cluster analysis by similarity of clinical phenotypes identified a cluster in which there was a higher number of women, and patients had more autoimmune features and a better prognosis than other clusters.These observations suggest that some patients with IIP show autoimmune features with distinct characteristics and favourable prognosis. However, we were not able to determine the appropriate therapies for these patients.
Abstract 2415: The role of GTSF1 as a regulator of retrotransposons and its impact on carcinogenesis
Authors: Amelia Martínez Villarreal, Jennifer Gantchev, Ivan Litvinov
Journal: Cancer Research (2021)

Abstract Hypomethylation of repetitive sequences is a common feature reported in cancer, particularly of retrotransposon elements. Retrotransposon elements can be deleterious due to their potential as insertional mutagens, so cells have deployed several control mechanisms to silence them through methylation of DNA. These methylation pathways are different between somatic and germline cells. In germline cells, the piRNA pathway is the main process responsible for silencing the retrotransposon LINE-1. GTSF1 is germline cell specific and an important part of this pathway. Along with PIWI proteins in the piRNA pathway, GTSF1 processes small RNA molecules and identifies active retrotransposons, recruiting the DNA methylation machinery to those sites. Aberrant expression of GTSF1 has been reported in cancer, particularly on lymphomas. We performed a Bayesian Analysis and Markov Chain Monte Carlo Method with GTSF1 levels of expression reported on The Cancer Genome Atlas (TCGA), which confirmed high levels of mRNA in lymphomas. Nonetheless, the role of GTSF1 in retrotransposon control in cancer and in carcinogenesis remains unknown. To address this issue, we have performed shRNA mediated knockdown in head and neck squamous cell carcinoma and cutaneous T-cell lymphoma cell lines, and we have overexpressed the cDNA of GTSF1 in immortalized keratinocytes. We evaluated the impact of the knockdown and overexpression on cell biology, retrotransposons, and genomic instability. Overall, GTSF1 expression seems to affect LINE-1 retrotransposon protein expression and function. Also, we are assessing the impact on genomic instability and methylation profiles. The aberrant expression of this gene poses an excellent clinical opportunity for targeted therapy development. Its germline cell restricted expression will potentially result in less secondary effects than current available therapies. Citation Format: Amelia Martínez Villarreal, Jennifer Gantchev, Ivan Litvinov. The role of GTSF1 as a regulator of retrotransposons and its impact on carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2415.
Abstract 2242: Blood-based genome-wide copy number analysis of 500 cancer patients
Authors: Chao Dai, Amy Xiaohong Wang, Zhixin Zhao, Feng Xie, Kemin Zhou, Shujun Luo, Shidong Jia, Pan Du
Journal: Cancer Research (2021)

Abstract Copy number variation (CNV) is an important characteristic in cancer genome. Blood-based low-pass whole genome sequencing (LP-WGS) has been increasingly used to identify copy number variations of large genomic ranges in cancer. Conventional LP-WGS data analysis lacks the identification of focal CNV of small genomic ranges and often includes biased estimation of copy-neutral baseline when unbalanced genome-wide copy number changes are present. In this study, we have developed a proprietary algorithm analysis pipeline and leverage PredicineCARE and PredicineATLAS panel-based sequencing platform to identify focal CNVs missed by LP-WGS, and accurately infer copy number neutral baseline for LP-WGS. Here we present plasma-based LP-WGS results from 500 cancer patients, including breast, prostate, pancreatic and lung cancers. Our study demonstrates a cancer type-specific pattern of copy number variation across chromosome arms. The CNV abnormality score we developed in this study can be used to distinguish healthy person from cancer patient, and monitor disease progression for longitudinal patient samples. Citation Format: Chao Dai, Amy Xiaohong Wang, Zhixin Zhao, Feng Xie, Kemin Zhou, Shujun Luo, Shidong Jia, Pan Du. Blood-based genome-wide copy number analysis of 500 cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2242.
New technique of robot-assisted laparoscopic artificial urinary sphincter implantation in female by a posterior approach with intraoperative cystoscopic monitoring
Authors: L. Broudeur, T. Loubersac, L. Le Normand, G. Karam, J. Branchereau, J. Rigaud, M-A. Perrouin-Verbe
Journal: European Urology (2021)
Comparison of clinicopathological characteristics between primary muscle-invasive bladder cancer and secondary muscle invasive bladder recurrence subsequent to upper tract urothelial carcinoma
Authors: K. Shigeta, K. Matsumoto, Y. Yasumizu, N. Tanaka, T. Takeda, T. Kosaka, R. Mizuno, E. Kikuchi, M. Oya
Journal: European Urology (2021)