tbuckley/cabot-search huggingface dataset:
Immunohistochemical PSMA expression patterns of primary prostate cancer tissue are associated with the detection rate of biochemical recurrence with <sup>68</sup>Ga-PSMA-11-PET
Authors: Daniela A. Ferraro, Jan H. Rüschoff, Urs J. Muehlematter, Benedikt Kranzbühler, Julian Müller, Michael Messerli, Lars Husmann, Thomas Hermanns, Daniel Eberli, Niels J. Rupp, Irene A. Burger
Journal: Theranostics (2020)

Prostate-specific membrane antigen (PSMA) targeted PET has a high detection rate for biochemical recurrence (BCR) of prostate cancer (PCa).Nevertheless, even at high prostate-specific antigen (PSA) levels (> 3 ng/ml), a relevant number of PSMA-PET scans are negative, mainly due to PSMA-negative PCa.Our objective was to investigate whether PSMA-expression patterns of the primary tumour on immunohistochemistry (IHC) are associated with PSMA-PET detection rate of recurrent PCa. Methods:Retrospective institutional review board approved single-centre analysis of patients who had undergone 68 Ga-PSMA-11-PET for BCR after radical prostatectomy (RPE) between 04/2016 and 07/2019, with tumour specimens available for PSMA-IHC.Clinical information (age, PSA-level, ongoing androgen deprivation therapy (ADT), Gleason score) and PSMA-IHC of the primary tumour were collected and their relationship to results from PSMA-PET (positive/negative) was investigated using a multiple logistic regression analysis.Results: 120 PSMA-PET scans in 74 patients were available for this analysis.Overall detection rate was 62% (74/120 scans), with a mean PSA value at scan time of 0.99 ng/ml .Of the clinical factors, only PSA-level and ADT were associated with PSMA-PET positivity.The percentage of PSMA-negative tumour area on IHC (PSMA%neg) had a significant association to PSMA-PET negativity (OR = 2.88, p < 0.001), while membranous PSMA-expression showed no association (p = 0.73).The positive predictive value of PSMA%neg ≥ 50% for a negative PSMA-PET was 85% (13/11) and for a PSMA%neg of 80% or more, 100% (9/9).Conclusions: PSMA-negative tumour area on IHC exhibited the strongest association with negative PSMA-PET scans, beside PSA-level and ADT.Even at very high PSA levels, PSMA-PET scans were negative in most of the patients with PSMA%neg ≥ 50%.
Consensus on Language for Advance Informed Consent in Health Care–Associated Pneumonia Clinical Trials Using a Delphi Process
Authors: Amy Corneli, Sara B. Calvert, John H. Powers, Teresa Swezey, Deborah Collyar, Brian Perry, John J. Farley, Jonas Santiago, Helen K. Donnelly, Carisa De Anda, Katelyn Blanchard, Vance G. Fowler, Thomas L. Holland
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Information to be included in advance informed consent forms for health care–associated pneumonia treatment trials remains to be determined. <h3>Objective</h3> To identify and determine how to describe information to be included in an advance informed consent form for an early-enrollment noninferiority hospital-acquired and/or ventilator-associated bacterial pneumonia (HABP/VABP) clinical trial. <h3>Design, Setting, and Participants</h3> A Delphi consensus process with stakeholders in HABP/VABP clinical trials was conducted using qualitative semistructured telephone interviews from June to August 2016, followed by 2 online surveys, the first from April to May 2017, and the second from September to October 2017. All stakeholders who participated in the interview were invited to participate in the first survey. Stakeholders who participated in the first survey were invited to participate in the second survey. Stakeholders were patients at risk of pneumonia, caregivers, representatives of institutional review boards, investigators, and study coordinators. <h3>Main Outcomes and Measures</h3> Description and consensus of information to be included in advance informed consent forms for early enrollment in noninferiority HABP/VABP clinical trials. <h3>Results</h3> Suggestions from 52 stakeholders about what key informed consent concepts to include and how to explain them were used to create 3 categories to be included in an advance consent form: (1) reassurances on patient health and treatment, (2) rationale for advance consent and early enrollment, and (3) an explanation of noninferiority. At the end of the Delphi process, at least 80% consensus was reached among the 40 stakeholders who participated in the second online survey on each of the statements to include in the proposed consent text. Throughout the process, however, describing and reaching consensus on statements about noninferiority was more problematic than the other categories. <h3>Conclusions and Relevance</h3> The stakeholders endorsed consent language to be used in combination with a strategy for enrolling patients at highest risk for pneumonia before infection onset. Data-driven consent language may help potential participants make informed decisions about their involvement in clinical research and improve enrollment rates, which are necessary to evaluate new treatments and improve patient care. The proposed consent language may be adapted for other trials using an early enrollment strategy and for noninferiority trials.
Role of Long Non-Coding RNAs in Reprogramming to Induced Pluripotency
Authors: Shahzina Kanwal, Xiangpeng Guo, Carl Ward, Giacomo Volpe, Baoming Qin, Miguel A. Esteban, Xichen Bao
Journal: Genomics Proteomics & Bioinformatics (2020)

Abstract The generation of induced pluripotent stem cells through somatic cell reprogramming requires a global reorganization of cellular functions. This reorganization occurs in a multi-phased manner and involves a gradual revision of both the epigenome and transcriptome. Recent studies have shown that the large-scale transcriptional changes observed during reprogramming also apply to long non-coding RNAs (lncRNAs), a type of traditionally neglected RNA species that are increasingly viewed as critical regulators of cellular function. Deeper understanding of lncRNAs in reprogramming may not only help to improve this process but also have implications for studying cell plasticity in other contexts, such as development, aging, and cancer. In this review, we summarize the current progress made in profiling and analyzing the role of lncRNAs in various phases of somatic cell reprogramming, with emphasis on the re-establishment of the pluripotency gene network and X chromosome reactivation.
Gastric biopsies in the assessment and management of patients at risk of gastric adenocarcinoma
Authors: Ian L P Beales
Journal: Gut (2020)

The recent BSG guideline on the diagnosis and management of patients at risk of gastric adenocarcinoma1 is a laudable attempt to bring some clarity to this often controversial area. The authors emphasised the importance of high-quality endoscopy with advanced imaging in the management of the patients with gastric atrophy (GA) and gastric intestinal metaplasia (GIM). However, it is still very difficult to relate most of the data presented to the British patient population and the guideline is rather lacking on the place in the pathway of gastric biopsies in establishing the diagnosis of GA or GIM. The guidance clearly focuses on using advanced imaging initially as assessment following an …
Abstract 13869: Immortalization of Human Neonatal C-kit+ Cardiac Progenitor Cells Preserves Their Phenotype and Function at High Passage
Authors: Emily L Ongstad, Rachana Mishra, Mehdi Belkhodja, Sudhish Sharma, Ranjitha Gaddipati, Sandrina Phipps, Sunjay Kaushal, Sotirios Karathanasis
Journal: Circulation (2019)

Introduction: There is significant controversy regarding the therapeutic potential of c-kit+ Cardiac Progenitor Cells (c-kit+ CPCs) for treatment of cardiac diseases. Previously we showed c-kit+ CP...
Bioengineered airway epithelial grafts with mucociliary function based on collagen IV- and laminin-containing extracellular matrix scaffolds
Authors: Nick J.I. Hamilton, Dani Do Hyang Lee, Kate H.C. Gowers, Colin R. Butler, Elizabeth F. Maughan, Benjamin Jevans, Jessica C. Orr, Conor J. McCann, Alan J. Burns, Sheila MacNeil, Martin A. Birchall, Christopher O'Callaghan, Robert E. Hynds, Sam M. Janes
Journal: European Respiratory Journal (2020)

Current methods to replace damaged upper airway epithelium with exogenous cells are limited. Existing strategies use grafts that lack mucociliary function, leading to infection and the retention of secretions and keratin debris. Strategies that regenerate airway epithelium with mucociliary function are clearly desirable and would enable new treatments for complex airway disease.Here, we investigated the influence of the extracellular matrix (ECM) on airway epithelial cell adherence, proliferation and mucociliary function in the context of bioengineered mucosal grafts. In vitro, primary human bronchial epithelial cells (HBECs) adhered most readily to collagen IV. Biological, biomimetic and synthetic scaffolds were compared in terms of their ECM protein content and airway epithelial cell adherence.Collagen IV and laminin were preserved on the surface of decellularised dermis and epithelial cell attachment to decellularised dermis was greater than to the biomimetic or synthetic alternatives tested. Blocking epithelial integrin α2 led to decreased adherence to collagen IV and to decellularised dermis scaffolds. At air-liquid interface (ALI), bronchial epithelial cells cultured on decellularised dermis scaffolds formed a differentiated respiratory epithelium with mucociliary function. Using in vivo chick chorioallantoic membrane (CAM), rabbit airway and immunocompromised mouse models, we showed short-term preservation of the cell layer following transplantation.Our results demonstrate the feasibility of generating HBEC grafts on clinically applicable decellularised dermis scaffolds and identify matrix proteins and integrins important for this process. The long-term survivability of pre-differentiated epithelia and the relative merits of this approach against transplanting basal cells should be assessed further in pre-clinical airway transplantation models.
Evidence for the Fundic Origin of Intrinsic Factor
Authors: Lawrence D. Wruble, G. William Cole, Howard E. Lessner, S. Z. Henrick Haidri, Martin H. Kalser
Journal: Annals of Internal Medicine (2020)

Excerpt The site of production of human gastric intrinsic factor has not been conclusively demonstrated. Previous studies have been done with either in vitro (1, 2) or postmortem speciments of huma...
Assessment of Discordance Between Surrogate Care Goals and Medical Treatment Provided to Older Adults With Serious Illness
Authors: Amber R. Comer, Susan E. Hickman, James E. Slaven, Patrick O. Monahan, Greg A. Sachs, Lucia D. Wocial, Emily S. Burke, Alexia M. Torke
Journal: JAMA Network Open (2020)

<h3>Importance</h3> An important aspect of high-quality care is ensuring that treatments are in alignment with patient or surrogate decision-maker goals. Treatment discordant with patient goals has been shown to increase medical costs and prolong end-of-life difficulties. <h3>Objectives</h3> To evaluate discordance between surrogate decision-maker goals of care and medical orders and treatments provided to hospitalized, incapacitated older patients. <h3>Design, Setting, and Participants</h3> This prospective cohort study included 363 patient-surrogate dyads. Patients were 65 years or older and faced at least 1 major medical decision in the medical and medical intensive care unit services in 3 tertiary care hospitals in an urban Midwestern area. Data were collected from April 27, 2012, through July 10, 2015, and analyzed from October 5, 2018, to December 5, 2019. <h3>Main Outcomes and Measures</h3> Each surrogate's preferred goal of care was determined via interview during initial hospitalization and 6 to 8 weeks after discharge. Surrogates were asked to select the goal of care for the patient from 3 options: comfort-focused care, life-sustaining treatment, or an intermediate option. To assess discordance, the preferred goal of care as determined by the surrogate was compared with data from medical record review outlining the medical treatment received during the target hospitalization. <h3>Results</h3> A total of 363 dyads consisting of patients (223 women [61.4%]; mean [SD] age, 81.8 [8.3] years) and their surrogates (257 women [70.8%]; mean [SD] age, 58.3 [11.2] years) were included in the analysis. One hundred sixty-nine patients (46.6%) received at least 1 medical treatment discordant from their surrogate's identified goals of care. The most common type of discordance involved full-code orders for patients with a goal of comfort (n = 41) or an intermediate option (n = 93). More frequent in-person contact between surrogate and patient (adjusted odds ratio [AOR], 0.43; 95% CI, 0.23-0.82), patient residence in an institution (AOR, 0.44; 95% CI, 0.23-0.82), and surrogate-rated quality of communication (AOR, 0.98; 95% CI, 0.96-0.99) were associated with lower discordance. Surrogate marital status (AOR for single vs married, 1.92; 95% CI, 1.01-3.66), number of family members involved in decisions (AOR for ≥2 vs 0-1, 1.84; 95% CI, 1.05-3.21), and religious affiliation (AOR for none vs any, 4.87; 95% CI, 1.12-21.09) were associated with higher discordance. <h3>Conclusions and Relevance</h3> This study found that discordance between surrogate goals of care and medical treatments for hospitalized, incapacitated patients was common. Communication quality is a modifiable factor associated with discordance that may be an avenue for future interventions.
APEC: an accesson-based method for single-cell chromatin accessibility analysis
Authors: Bin Li, Young Li, Kun Li, Lianbang Zhu, Qiaoni Yu, Pengfei Cai, Jingwen Fang, Wen Zhang, Pengcheng Du, Chen Jiang, Jun Lin, Kun Qu
Journal: Genome biology (2020)

Abstract The development of sequencing technologies has promoted the survey of genome-wide chromatin accessibility at single-cell resolution. However, comprehensive analysis of single-cell epigenomic profiles remains a challenge. Here, we introduce an accessibility pattern-based epigenomic clustering (APEC) method, which classifies each cell by groups of accessible regions with synergistic signal patterns termed “accessons”. This python-based package greatly improves the accuracy of unsupervised single-cell clustering for many public datasets. It also predicts gene expression, identifies enriched motifs, discovers super-enhancers, and projects pseudotime trajectories. APEC is available at https://github.com/QuKunLab/APEC .
Carcinogenicity of Different Polycyclic Hydrocarbons in the Respiratory Tract of Hamsters&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: D A Silverman, N R Rose
Journal: JNCI Journal of the National Cancer Institute (1974)

Buffalo (BUF) strain rats developed autoimmune thyroiditis spontaneously and the incidence was increased by administration of 3-methylcholanthrene (MCA). MCA did not alter the response of BUF rats to sheep red blood cells in terms of antibody titers or plaque-forming cells. However, hypersensitivity to BCG was reduced and thymus weight decreased significantly.
Reversal of prolonged obesity-associated cerebrovascular dysfunction by inhibiting microglial Tak1
Authors: Qing Shen, Zhuo Chen, Faming Zhao, Susu Pan, Tingting Zhang, Xueer Cheng, Lei Zhang, Shanshan Zhang, Junxia Qi, Juxue Li, Dongsheng Cai, Guo Zhang
Journal: Nature Neuroscience (2020)
Abstract 104: N-Acetyl Cysteine Improves Post Reperfusion Myocardial Dysfunction in a Rat Model of Cardiac Arrest and Return of Spontaneous Circulation
Authors: Fenglian He
Journal: Circulation (2018)

N-acetylcysteine improves post reperfusion myocardial dysfunction in a Rat Model of Cardiac Arrest and return of spontaneous circulation Introduction: Studies have demonstrated that N-acetylcysteine (NAC) can attenuate regional myocardial ischemia/reperfusion injury and improved myocardial dysfunction. However, it is not clear whether NAC could protect post reperfusion myocardial dysfunction (PRMD) after cardiac arrest (CA) and return of spontaneous circulation (ROSC). In this study, we investigated the effect of NAC on post reperfusion myocardial dysfunction in a rat model of CA and ROSC. Hypothesis: NAC reduces the severity of PRMD in a rat model of CA and ROSC. Method: Ten healthy male Sprague-Dawley rats weighting 450g–550g were utilized, and randomly divided into two groups: 1) control group; 2) NAC group (150mg/kg). Ventricular fibrillation (VF) was induced. After 8 mins of VF, CPR was initiated for 8 mins, and defibrillation was then attempted. Myocardial function was measured by echocardiography at baseline, 2, 4 and 6 hours after successful resuscitation. Result: Except one in the control group, all animals were resuscitated. Myocardial function of post-resuscitation was significantly decreased in all animals. However, myocardial function gradually improved in animals treated with NAC when compared with those in control groups (Figure). Conclusion: In a rat model of cardiac arrest, NAC improves post-resuscitation myocardial dysfunction Figure The post-resuscitation myocardial dysfunction. BL, baseline; VF, ventricular fibrillation; CO, cardiac output; EF, ejection fraction; MPI, myocardial performance index; CPR, cardiopulmonary resuscitation; C group,control group; N group, NAC intervention group; * p &lt; 0.05.vs. the C group.
Covid-19: Public health must be “at the core” of global recovery plans, say doctors
Authors: Gareth Iacobucci
Journal: BMJ (2020)

Global health leaders have urged governments to put public health “at the core” of economic recovery from covid-19.

In a joint letter1 to all G20 heads of state, organisations representing over 40 million doctors, nurses, and other health professionals say national economic stimulus packages should be designed and approved by medical and scientific leaders, to ensure that “short and long term public health repercussions” are prioritised in policy making.

The letter, coordinated by the Global Climate and Health Alliance, the Every Breath Matters campaign, and the World Health Organisation, says that the covid-19 pandemic has exposed the vulnerability of communities when health, food security, …
Adenovirus Infections in Children and Young Adults
Authors: Alfred S. Evans
Journal: New England Journal of Medicine (1958)

RESPIRATORY infections due to adenoviruses have a high incidence in military recruits,1 2 3 but increasing evidence indicates they are responsible for little clinical illness in civilian populations.4 5 6 7 8 9 This paper presents the results of two additional studies of civilian groups: a summary of a four-year investigation of 710 university students hospitalized with acute respiratory disease‡ from 1954–1958; and a survey of the prevalence of adenoviruses in third-grade school children over a three-month period.§The findings of these investigations will be compared with similar studies as a basis for recommendations for use of adenovirus vaccine. I agree with the recently published views of . . .
Obesity Phenotypes, Diabetes, and Cardiovascular Diseases
Authors: Marie-Eve Piché, André Tchernof, Jean-Pierre Després
Journal: Circulation Research (2020)

This review addresses the interplay between obesity, type 2 diabetes mellitus, and cardiovascular diseases. It is proposed that obesity, generally defined by an excess of body fat causing prejudice to health, can no longer be evaluated solely by the body mass index (expressed in kg/m 2 ) because it represents a heterogeneous entity. For instance, several cardiometabolic imaging studies have shown that some individuals who have a normal weight or who are overweight are at high risk if they have an excess of visceral adipose tissue—a condition often accompanied by accumulation of fat in normally lean tissues (ectopic fat deposition in liver, heart, skeletal muscle, etc). On the other hand, individuals who are overweight or obese can nevertheless be at much lower risk than expected when faced with excess energy intake if they have the ability to expand their subcutaneous adipose tissue mass, particularly in the gluteal-femoral area. Hence, excessive amounts of visceral adipose tissue and of ectopic fat largely define the cardiovascular disease risk of overweight and moderate obesity. There is also a rapidly expanding subgroup of patients characterized by a high accumulation of body fat (severe obesity). Severe obesity is characterized by specific additional cardiovascular health issues that should receive attention. Because of the difficulties of normalizing body fat content in patients with severe obesity, more aggressive treatments have been studied in this subgroup of individuals such as obesity surgery, also referred to as metabolic surgery. On the basis of the above, we propose that we should refer to obesities rather than obesity.
Cardio-Oncology in Brazil
Authors: Ludhmila Abrahão Hajjar, MD, PhD, Clarissa Mathias, MD, PhD
Journal: JACC CardioOncology (2020)

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Occupying nearly one-half of South America’s landmass, Brazil is the largest country of the continent. The country has a diverse range of tropical and subtropical regions, with wetlands, grassy plains (known as savannahs), and low mountainous landscapes.
156P Matching-adjusted indirect comparison (MAIC) of palbociclib versus ribociclib and abemaciclib in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2 ABC)
Authors: H.S. Rugo, A. Haltner, L. Zhan, A. Tran, E. Bananis, D. Mitra, C. Cameron
Journal: Annals of Oncology (2020)
Addition of Neutral Protamine Lispro Insulin or Insulin Glargine to Oral Type 2 Diabetes Regimens for Patients with Suboptimal Glycemic Control
Authors: Katherine Esposito, Miryam Ciotola, Maria Ida Maiorino, Roberto Gualdiero, Bruno Schisano, Antonio Ceriello, Flora Beneduce, Giovanni Feola, Dario Giugliano
Journal: Annals of Internal Medicine (2008)

Many patients with type 2 diabetes that is poorly controlled with oral agents take bedtime insulin. In 2 previous trials, neutral protamine lispro (NPL) insulin achieved better glycemic control tha...
Turning weakness into strength: Albumin nanoparticle-redirected amphotericin B biodistribution for reducing nephrotoxicity and enhancing antifungal activity
Authors: Yanchao Liu, Yi Han, Ting Fang, Si-Min Chen, Xinyu Hu, Lijun Song, Hui Shen, Haiqing Dong, Yuan-Ying Jiang, Zui Zou, Yongyong Li, Mao-Mao An
Journal: Journal of Controlled Release (2020)