tbuckley/cabot-search huggingface dataset:
Obesity and revision surgery, mortality, and patient-reported outcomes after primary knee replacement surgery in the National Joint Registry: A UK cohort study
Authors: Jonathan Thomas Evans, Sofia Mouchti, Ashley William Blom, Jeremy Mark Wilkinson, Michael Richard Whitehouse, Andrew Beswick, Andrew Judge
Journal: PLoS Medicine (2021)

Background One in 10 people in the United Kingdom will need a total knee replacement (TKR) during their lifetime. Access to this life-changing operation has recently been restricted based on body mass index (BMI) due to belief that high BMI may lead to poorer outcomes. We investigated the associations between BMI and revision surgery, mortality, and pain/function using what we believe to be the world’s largest joint replacement registry. Methods and findings We analysed 493,710 TKRs in the National Joint Registry (NJR) for England, Wales, Northern Ireland, and the Isle of Man from 2005 to 2016 to investigate 90-day mortality and 10-year cumulative revision. Hospital Episodes Statistics (HES) and Patient Reported Outcome Measures (PROMs) databases were linked to the NJR to investigate change in Oxford Knee Score (OKS) 6 months postoperatively. After adjustment for age, sex, American Society of Anaesthesiologists (ASA) grade, indication for operation, year of primary TKR, and fixation type, patients with high BMI were more likely to undergo revision surgery within 10 years compared to those with “normal” BMI (obese class II hazard ratio (HR) 1.21, 95% CI: 1.10, 1.32 ( p &lt; 0.001) and obese class III HR 1.13, 95% CI: 1.02, 1.26 ( p = 0.026)). All BMI classes had revision estimates within the recognised 10-year benchmark of 5%. Overweight and obese class I patients had lower mortality than patients with “normal” BMI (HR 0.76, 95% CI: 0.65, 0.90 ( p = 0.001) and HR 0.69, 95% CI: 0.58, 0.82 ( p &lt; 0.001)). All BMI categories saw absolute increases in OKS after 6 months (range 18–20 points). The relative improvement in OKS was lower in overweight and obese patients than those with “normal” BMI, but the difference was below the minimal detectable change (MDC; 4 points). The main limitations were missing BMI particularly in the early years of data collection and a potential selection bias effect of surgeons selecting the fitter patients with raised BMI for surgery. Conclusions Given revision estimates in all BMI groups below the recognised threshold, no evidence of increased mortality, and difference in change in OKS below the MDC, this large national registry shows no evidence of poorer outcomes in patients with high BMI. This study does not support rationing of TKR based on increased BMI.
移動と健康を研究するための英国プライマリケア電子健康記録の使用の妥当性:集団ベースのコホート研究【JST・京大機械翻訳】
Authors: Pathak Neha, Burns Rachel, Gonzalez-Izquierdo Arturo, Denaxas Spiros, Sonnenberg Pam, Hayward Andrew, Aldridge Robert
Journal: The Lancet (2019)
A Biomimetic In Vitro Model of the Kidney Filtration Barrier Using Tissue‐Derived Glomerular Basement Membrane
Authors: Dan Wang, Snehal Sant, Nicholas Ferrell
Journal: Advanced Healthcare Materials (2021)

Abstract The glomerular filtration barrier (GFB) filters the blood to remove toxins while retaining high molecular weight proteins in the circulation. The glomerular basement membrane (GBM) and podocytes, highly specialized epithelial cells, are critical components of the filtration barrier. The GBM serves as a physical barrier to passage of molecules into the filtrate. Podocytes adhere to the filtrate side of the GBM and further restrict passage of high molecular weight molecules into the filtrate. Here, a 3D cell culture model of the glomerular filtration barrier to evaluate the role of the GBM and podocytes in mediating molecular diffusion is developed. GBM is isolated from mammalian kidneys to recapitulate the composition and mechanics of the in vivo basement membrane. The GFB model exhibits molecular selectivity that is comparable to the in vivo filtration barrier. The GBM alone provides a stringent barrier to passage of albumin and Ficoll. Podocytes further restrict molecular diffusion. Damage to the GBM that is typical of diabetic kidney disease is simulated using hypochlorous acid and results in increased molecular diffusion. This system can serve as a platform to evaluate the effects of GBM damage, podocyte injury, and reciprocal effects of altered podocyte–GBM interactions on kidney microvascular permeability.
Abstract 2405: Metabolic plasticity of ovarian metastases in response to adherence and physiologically relevant culture conditions
Authors: Stephanie Edwards Compton, Joseph Grieco, Eva M. Schmelz
Journal: Cancer Research (2021)

Abstract Ovarian cancer is typically diagnosed at late stages with a poor prognosis due to high recurrence. Exfoliation from the primary tumor results in aggregation of ovarian cancer cells into spheroids in the peritoneal cavity, which then adhere to secondary sites to form metastatic outgrowth. Spheroids in the peritoneal cavity are exposed to hypoxic, low glucose conditions. Sphingosine-1-phosphate (S1P), increased in the ascites fluid of ovarian cancer patients, has been shown to increase tumor cell survival and tumorigenesis through changes in mitochondrial function. However, little is known about these effects in ovarian cancer spheroids, particularly upon secondary adherence and outgrowth in physiological conditions. Changes in spheroid metabolism in response to treatment with S1P, hypoxia, low glucose, and obese peritoneal serous fluid (PSF) in both free and adherent states was investigated. Using a late-stage and tumor-initiating murine ovarian cancer model, spheroids were subjected to treatment with S1P or obese PSF as free or adherent spheroids. Using a Seahorse XFe96, we investigated changes in metabolism over time trials measured after 24 hour treatment for free spheroids and after different time points of adherence (4, 8, 12, and 24 hours). Data show changes in basal respiration, maximal oxygen consumption rate, and spare respiratory capacity of spheroids over adherence time when treated with S1P and PSF. This suggests that the cells respond to energetic demand with metabolic flexibility as the spheroids adhere to new surfaces. The identification of the regulation of these events may help elucidate the flexibility that takes place during metastasis in culture that more closely mimics physiological conditions, providing a foundation for future interventions for preventative therapies for ovarian cancer with dietary sphingolipids and possible treatment targets. Citation Format: Stephanie Edwards Compton, Joseph Grieco, Eva M. Schmelz. Metabolic plasticity of ovarian metastases in response to adherence and physiologically relevant culture conditions [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 2405.
No Evidence to Favor 99mTc-HMPAO or 99mTc-ECD for Ictal Brain Perfusion SPECT for Identification of the Seizure Onset Zone
Authors: Mariam Jaber, Jila Taherpour, Berthold Voges, Ivayla Apostolova, Thomas Sauvigny, Patrick M. House, Michael Lanz, Matthias Lindenau, Susanne Klutmann, Tobias Martens, Stefan Stodieck, Ralph Buchert
Journal: Clinical Nuclear Medicine (2021)

Ictal brain perfusion SPECT with the tracer 99mTc-HMPAO or 99mTc-ECD is widely used for identification of the epileptic seizure onset zone (SOZ) in presurgical evaluation if standard pointers are uncertain or inconsistent. For both tracers, there are theoretical arguments to favor it over the other for this task. The aim of this study was to compare the performance of ictal brain perfusion SPECT between 99mTc-HMPAO and 99mTc-ECD in a rather large patient sample.The study retrospectively included 196 patients from clinical routine in whom ictal perfusion SPECT had been performed with stabilized 99mTc-HMPAO (n = 110) or 99mTc-ECD (n = 86). Lateralization and localization of the SOZ were obtained by the consensus of 2 independent readers based on visual inspection of the SPECT images.The 99mTc-HMPAO group and the 99mTc-ECD group were well matched with respect to age, sex, age at first seizure, duration of disease, seizure frequency, history of previous brain surgery, and findings of presurgical MRI. The proportion of lateralizing ictal SPECT did not differ significantly between 99mTc-HMPAO and 99mTc-ECD (65.5% vs 72.1%, P = 0.36). Sensitivity of ictal perfusion SPECT (independent of the tracer) for correct localization of the SOZ in 62 patients with temporal lobe epilepsy and at least worthwhile improvement (Engel scale ≤ III) 12 months after temporal epilepsy surgery was 63%.This study does not provide evidence to favor 99mTc-HMPAO or 99mTc-ECD for identification of the SOZ by ictal perfusion SPECT.
Abstract 12063: Electrical Cardioversion for Atrial Fibrillation; Initial and Subsequent Change in Transthoracic Impedance Predicts the Likelihood to Require Charge Escalation to High Energies During External Defibrillation
Authors: Assad Mohammedzein, Katie Walsh, Abushama Abubakr, Patrick Owens
Journal: Circulation (2019)

Introduction: Transthoracic cardioversion (CV) continues to be the most effective method of rhythm control for atrial fibrillation (AF) and flutter (AFL). However, little is known about the effect ...
Biomaterial vaccines capturing pathogen-associated molecular patterns protect against bacterial infections and septic shock
Authors: Michael Super, Edward J. Doherty, Mark J. Cartwright, Benjamin T. Seiler, Fernanda Langellotto, Nikolaos Dimitrakakis, Des A. White, Alexander G. Stafford, Mohan Karkada, Amanda R. Graveline, Caitlin L. Horgan, Kayla R. Lightbown, Frank R. Urena, Chyenne D. Yeager, Sami A. Rifai, Maxence O. Dellacherie, Aileen W. Li, Collin Leese-Thompson, Hamza Ijaz, Amanda R. Jiang, Vasanth Chandrasekhar, Justin M. Scott, Shanda L. Lightbown, Donald E. Ingber, David J. Mooney
Journal: Nature Biomedical Engineering (2021)
Erectile Dysfunction (ED) prevalence, risk factors, comorbid chronic conditions, and quality of life burden in the UK general population
Authors: T.A. Maguire, J.Z. Li, M.C. Maculaitis, K.H. Zou, L.J. Lee, V.W. Li, M. Jeffress, S. Donde, D.G. Taylor
Journal: European Urology (2021)
Role of Liver Resection for Hepatocellular Carcinoma with Vascular Invasion: Emerging Evidence from Western Countries
Authors: Norihiro Kokudo, Takashi Kokudo, Kiyoshi Hasegawa
Journal: Liver Cancer (2021)

Patients with advanced hepatocellular carcinoma (HCC) with macrovascular invasion, that is, tumor thrombosis in the portal vein or hepatic vein, are generally considered not eligible for liver resection in Western countries, and only systemic therapy is recommended. However, there is a subgroup of patients who can survive long after surgical treatment despite having a very advanced stage of the disease. Some Asian surgical centers and a few Western surgical centers have been using surgery to treat BCLC stage C HCC as long as it is operable, and those centers have reported acceptable outcomes. In this issue of &lt;i&gt;Liver Cancer&lt;/i&gt;, Govalan et al. report on the superiority of surgical resection over other treatments for patients with vascular invasion based on data from the National Cancer Database. This is a first report analyzing a large set of contemporary US cohort data, and its findings may catch the attention of many hepatologists in Western countries who are hesitant about sending eligible patients to surgeons. In this era of advanced systemic therapy using molecular targeted agents and immuno-check point inhibitors, a combination of promising systemic therapy and surgery may be a future path to improve survival for patients with this very advanced disease.
多孔性RNAナノスフェアのシクロデキストリン仲介形成と肝細胞癌の相乗的標的治療への応用【JST・京大機械翻訳】
Authors: Chen Xiaoxia, Chen Tianshu, Zhang Lili, Wang Zhenyu, Zhou Qingqing, Huang Tingting, Ge Chao, Xu Huili, Zhu Miaoxin, Zhao Fangyu, Yao Ming, Tian Hua, Li Hong, Zhu Xiaoli, Li Jinjun
Journal: Biomaterials (2020)
Abstract 8268: Sickness Behavior Predicts Event Free Survival in Adults with Heart Failure
Authors: Barbara Riegel, Sarah J Ratcliffe
Journal: Circulation (2011)

Stimulation of the immune system produces a non-specific cluster of symptoms referred to as sickness behavior. Numerous and diverse systemic conditions stimulate the immune system and produce this response, including heart failure (HF). Purpose: The purpose of this study was to explore the ability of the sickness behavior symptom cluster to predict event-free survival 6 months later in adults with HF. Methods: A sample of 280 adults with stage C HF was enrolled from 3 sites in the Northeastern US. Those with dementia, terminal illness, a recent history of drug or alcohol abuse, and night shift workers were excluded. NYHA functional class was measured at baseline. Sickness behaviors, defined as an aggregate of fatigue, sleepiness, and depression, were measured at baseline, aggregated using factor analysis. Hospitalizations were measured by self-report and validated in the medical record. Deaths were confirmed in the medical record or the US death records. The influence of sickness behavior on event free survival (hospitalization, death) was analyzed with multivariable Cox proportional hazards regression. Results: A total of 97 events (6 deaths) occurred during the 6-months of follow-up in the 274 subjects with follow-up data available. When the analysis was stratified by NYHA class, sickness behavior was a significant predictor of the risk for death or hospitalization for subjects in NYHA class IV (n=48, RR=1.67, p=0.011) but not in the other NYHA classes. Conclusion: Adults with NYHA class IV HF who manifest sickness behavior are more likely to be hospitalized or die than those without the sickness behavior symptom cluster. Study of the factors associated with sickness behavior may suggest targets for intervention. Further study of this indicator of immune dysfunction may help integrate disparate observations regarding fatigue, sleepiness, and depression in HF patients.
Risk factors for IRIS in HIV-associated Pneumocystis-pneumonia following ART initiation
Authors: Gerrit Kann, Nils Wetzstein, Hannah Bielke, Gundolf Schuettfort, Annette E. Haberl, Timo Wolf, Claus P. Kuepper-Tetzel, Imke Wieters, Johanna Kessel, Philipp de Leuw, Markus Bickel, Pavel Khaykin, Christoph Stephan
Journal: Journal of Infection (2021)
A Pilot Study Evaluating the Impact of Hospital Hospitality Houses (HHH) Programs on the Quality of Life and Mood of Patients and Their Caregivers Following Hematopoietic Stem Cell Transplant (HCT)
Authors: Maria Emma Torres, Shahrukh K. Hashmi, Angelina Tan, Jeff A. Sloan, Maria Stevens, Valerie Callahan, Gerardo Colon-Otero
Journal: Blood (2017)
The Pannexin 1/Purinergic Receptor P2X4 Pathway Controls the Secretion of MicroRNA‐Containing Exosomes by HCV‐Infected Hepatocytes
Authors: Ok‐Kyung Kim, Da‐eun Nam, Young S. Hahn
Journal: Hepatology (2021)

Background and Aims HCV infection is a major risk factor that can lead to chronic liver disease, including fibrosis, cirrhosis, and HCC. Progression of chronic liver disease by HCV infection is caused by a complex intercellular reaction. Especially, exosomes and microRNAs (miRNAs) from HCV‐infected hepatocytes play a role in the pathogenesis of liver disease by facilitating cellular communication between parenchymal and nonparenchymal cells. However, the underlying mechanism of secretions of exosome and miRNAs during HCV infection is still open for study. Approach and Results In this study, we demonstrated a pathway for the release of exosome and exosomal miRNAs through caspase‐3/pannexin 1 (Panx1)/P2X4 activation during HCV infection in hepatocytes. We found that HCV infection induced the stimulation of exosome release and activation of the caspase‐3/Panx1/P2X4 pathway in Huh7.5.1 cells. In addition, miR‐122 and miR‐146a levels in extracellular exosomes from HCV‐infected cells were dramatically increased whereas intracellular miR122 and miR‐146a expression had no large changes. Notably, secretions of exosomes and exosomal miRNAs were decreased by inhibition of caspase 3, Panx1, and P2X4 whereas inhibition of ROCK‐1 cleavage did not affect these during HCV infection in Huh7.5.1 cells. Conclusions These results suggested that HCV infection caused secretions of exosomes and exosomal miRNAs dependent on the caspase 3/Panx1/P2X4 pathway. Our study provides a possible therapeutic intervention using Panx1 suppression for liver disease development mediated by exosomes from HCV‐infected hepatocytes.
First-line treatments for cisplatin-eligible patients with metastatic urothelial carcinoma: A meta-analysis
Authors: K. Mori, B. Pradere, M. Moschini, H. Mostafaei, E. Laukhtina, V.M. Schuettfort, R. Sari Motlagh, F. Soria, J.Y.C. Teoh, F. Quhal, S. Katayama, S. Egawa, T. Powles, S.F. Shariat
Journal: European Urology (2021)
Abstract 1287: Novel NSAID derivatives containing selenium as potent cytotoxic agents against cancer
Authors: Sandra Ramos-Inza, Ignacio Encío, Arun K. Sharma, Carmen Sanmartín, Daniel Plano
Journal: Cancer Research (2021)

Abstract Cancer is currently one of the major health problems of the human population and a prominent cause of death worldwide. The introduction of a selenium atom (Se) in the structure of organic molecules has demonstrated to be a valid approximation in the design of novel chemotherapeutic agents with several biological effects, including antitumoral activity. On the other hand, non-steroidal anti-inflamatory drugs (NSAIDs) have gained interest in recent years in terms of their chemopreventive and chemotherapeutic activities, whether when they are evaluated alone, as a combination therapy, or in the form of structurally modified analogs.On the basis of these findings, and taking into account the results of previous studies by our research group, we have developed a new series of twenty-five NSAID analogs bearing Se in their structure with several variations. The new compounds were tested in four cancer cell lines (HTB-54, DU-145, HT-29 and MCF-7) and two non-malignant cells (184B5 and BEAS-2B), showing promising results with IC50 values below 10 μM. The cytotoxicity of the five most potent and selective molecules was further studied in other cancer cell lines as well. Taken together, this work supports the design of new derivatives containing Se as potential antitumoral agents. Citation Format: Sandra Ramos-Inza, Ignacio Encío, Arun K. Sharma, Carmen Sanmartín, Daniel Plano. Novel NSAID derivatives containing selenium as potent cytotoxic agents against 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 1287.
Lung transplantation for acute exacerbation of interstitial lung disease
Authors: Mwelwa Chizinga, Tiago N Machuca, Abbas Shahmohammadi, Divya C Patel, Ayoub Innabi, Bashar Alzghoul, Vanessa Scheuble, Mauricio Pipkin, Borna Mehrad, Andres Pelaez, Christine Lin, Diana Gomez- Manjarres
Journal: Thorax (2021)

Background Acute exacerbations of interstitial lung diseases (AE-ILD) have a high mortality rate with no effective medical therapies. Lung transplantation is a potentially life-saving option for patients with AE-ILD, but its role is not well established. The aim of this study is to determine if this therapy during AE-ILD significantly affects post-transplant outcomes in comparison to those transplanted with stable disease. Methods We conducted a retrospective study of consecutive patients with AE-ILD admitted to our institution from 2015 to 2018. The comparison group included patients with stable ILD listed for lung transplant during the same period. The primary end-points were in-hospital mortality for patients admitted with AE-ILD and 1-year survival for the transplanted patients. Results Of 53 patients admitted for AE-ILD, 28 were treated with medical therapy alone and 25 underwent transplantation. All patients with AE-ILD who underwent transplantation survived to hospital discharge, whereas only 43% of the AE-ILD medically treated did. During the same period, 67 patients with stable ILD underwent transplantation. Survival at 1 year for the transplanted patients was not different for the AE-ILD group versus stable ILD group (96% vs 92.5%). The rates of primary graft dysfunction, post-transplant hospital length-of-stay and acute cellular rejection were similar between the groups. Conclusion Patients with ILD transplanted during AE-ILD had no meaningful difference in overall survival, rate of primary graft dysfunction or acute rejection compared with those transplanted with stable disease. Our results suggest that lung transplantation can be considered as a therapeutic option for selected patients with AE-ILD.
Mevalonate Blockade in Cancer Cells Triggers CLEC9A+ Dendritic Cell-Mediated Antitumor Immunity
Authors: Feifei Xu, Zining Wang, Hongxia Zhang, Jiemin Chen, Xiaojuan Wang, Lei Cui, Chunyuan Xie, Mengyun Li, Fang Wang, Penghui Zhou, Jinyun Liu, Peng Huang, Xiaodong Xia, Xiaojun Xia
Journal: Cancer Research (2021)

Abstract Hyperactive mevalonate (MVA) metabolic activity is often observed in cancer cells, and blockade of this pathway inhibits tumor cell lipid synthesis and cell growth and enhances tumor immunogenicity. How tumor cell MVA metabolic blockade promotes antitumor immune responses, however, remains unclear. Here we show that inhibition of the MVA metabolic pathway in tumor cells elicits type 1 classical dendritic cells (cDC1)–mediated tumor recognition and antigen cross-presentation for antitumor immunity. Mechanistically, MVA blockade disrupted prenylation of the small GTPase Rac1 and induced cancer cell actin filament exposure, which was recognized by CLEC9A, a C-lectin receptor specifically expressed on cDC1s, in turn activating antitumor T cells. MVA pathway blockade or Rac1 knockdown in tumor cells induced CD8+ T-cell-mediated antitumor immunity in immunocompetent mice but not in Batf3−/− mice lacking CLEC9A+ dendritic cells. These findings demonstrate tumor MVA metabolic blockade stimulates a cDC1 response through CLEC9A-mediated immune recognition of tumor cell cytoskeleton, illustrating a new immune surveillance mechanism by which dendritic cells monitor tumor metabolic dysregulation and providing insight into how MVA pathway inhibition may potentiate anticancer immunity. Significance: These findings suggest that mevalonate blockade in cancer cells disrupts Rac1 prenylation to increase recognition and cross-presentation by conventional dendritic cells, suggesting this axis as a potential target for cancer immunotherapy.
The Role of Matrix Metalloproteinase-9 in Monocytic Myeloid-Derived Suppressor Cells in Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Sung-Eun Lee, Ji-Young Lim, Tae Woo Kim, Young-Woo Jeon, Jae-Ho Yoon, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Seok Lee, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min, Dong-Mi Shin, Eun Young Choi, Chang-Ki Min
Journal: Blood (2017)