tbuckley/cabot-search huggingface dataset:
Which outcomes are reported in cellulitis trials? Results of a review of outcomes included in cellulitis trials and a patient priority setting survey
Authors: E. Smith, M. Patel, K.S. Thomas
Journal: British Journal of Dermatology (2017)

There is an emerging need to develop consistent outcomes in clinical trials to allow effective comparison of treatment effects. No systematic review has previously looked at the reporting of outcome measures used in randomized controlled trials (RCTs) on the treatment and prevention of cellulitis (erysipelas). The primary aim of this review was to describe the breadth of outcomes reported from RCTs on cellulitis treatment and prevention. The secondary aim was to identify outcome themes from patients' and healthcare professionals' feedback from a cellulitis Priority Setting Partnership (PSP). We conducted a review of all outcome measures used in RCTs from two recent Cochrane reviews. Free‐text responses from a cellulitis priority setting survey were used to understand the perspectives of patients and healthcare professionals. Outcomes from 42 RCTs on treatment of cellulitis and six RCTs on prevention of cellulitis were reviewed. Only 28 trials stated their primary outcome. For trials assessing treatment of cellulitis, clinical response to treatment was categorized in 25 different ways. Five of these trials used an outcome that was in accordance with FDA guidance and only four trials incorporated either quality of life or patient satisfaction. For trials assessing prevention of cellulitis, recurrence was the key outcome measure. From the cellulitis PSP, prevention of recurrence, clinical features and long‐term disease impact were the most important outcome themes for patients. We have shown that in cellulitis treatment and prevention research, there is significant heterogeneity in clinical outcomes, inadequate focus on patient‐reported outcomes, and a disparity between what is currently measured and what patients and healthcare professionals feel is important. We recommend that future cellulitis treatment trials consider the use of longer‐term outcomes to capture recurrence and long‐term morbidity, as well as short‐term resolution of acute infection.
Efficacy and safety of rituximab for systemic lupus erythematosus‐associated immune cytopenias: A multicenter retrospective cohort study of 71 adults
Authors: Alexandra Serris, Zahir Amoura, Florence Canouï‐Poitrine, Benjamin Terrier, Eric Hachulla, Nathalie Costedoat‐Chalumeau, Thomas Papo, Olivier Lambotte, David Saadoun, Miguel Hié, Philippe Blanche, Bertrand Lioger, Jacques‐Eric Gottenberg, Bertrand Godeau, Marc Michel
Journal: American Journal of Hematology (2017)

Abstract The aim of the study was to assess the efficacy and safety of rituximab (RTX) for treating systemic lupus erythematosus (SLE)‐associated immune cytopenias. This multicenter retrospective cohort study of adults from French referral centers and networks for adult immune cytopenias and SLE involved patients ≥18 years old with a definite diagnosis of SLE treated with RTX specifically for SLE‐associated immune cytopenia from 2005 to 2015. Response assessment was based on standard definitions. In total, 71 patients, 61 women (85.9%), with median age 36 years [interquartile range 31‐48], were included. The median duration of SLE at the time of the first RTX administration was 6.1 years [2.6‐11.6] and the reason for using RTX was immune thrombocytopenia (ITP) for 44 patients (62.0%), autoimmune hemolytic anemia (AIHA) for 16 (22.5%), Evans syndrome for 10 (14.1%), and pure red cell aplasia for one patient. Before receiving RTX, patients had received a mean of 3.1 ± 1.3 treatments that included corticosteroids (100%), and hydroxychloroquine (88.5%). The overall initial response rate to RTX was 86% (91% with ITP, 87.5% with AIHA, and 60% with Evans syndrome), including 60.5% with complete response. Median follow‐up after the first injection of RTX was 26.4 months [14.3‐71.2]. Among 61 initial responders, relapse occurred in 24 (39.3%); for 18, RTX retreatment was successful in 16 (88.8%). Severe infections occurred after RTX in three patients, with no fatal outcome. No cases of RTX‐induced neutropenia were observed. In conclusion, RTX seems effective and relatively safe for treating SLE‐associated immune cytopenias.
Abstract 17084: Clinical Experience With the Subcutaneous Implantable Cardioverter Defibrillator in Paediatric Patients
Authors: Reinoud Knops, Tom Brouwer
Journal: Circulation (2015)

Introduction: In pediatric patients prevention of Sudden Cardiac Death (SCD) using Implantable Cardioverter Defibrillators (ICD) is associated with a higher risk of complications than in the adult population. Surgical re-interventions due to infection, lead dislocation or migration and inappropriate shocks on intra and extracardiac oversensing are the most prevalent complications. The Subcutaneous ICD (S-ICD) has been introduces as a less invasive and extravascular alternative to overcome some of these complications. The scientific data that has led to the approval of the S-ICD did not include pediatric patients. Contradicting reports in small cohorts have been published on the effectiveness of S-ICD therapy in the pediatric population. We here report the largest pediatric cohort with the longest follow up to date where the S-ICD has been used for SCD prevention. Hypothesis: The S-ICD is safe and effective for the prevention of SCD in a diverse pediatric population. Methods: We retrospectively studied all consecutive pediatric patients (age&lt;18 yrs)that were implanted with a S-ICD in our center. Results: Fifteen S-ICDs were implanted in 14 patients (mean age 14, range 8-17), 71% were male, mean BMI was 18.8 (range 17.2-28.8), 57% had a secondary prevention indication, 77% had a genetic arrhythmia diagnosis and the median follow up was 21 months (range 1- 57). The first shock efficacy of induced and spontaneous episodes was 100% (n=13 and n =2 respectively). Inappropriate shocks due to intracardiac oversensing occurred in 3 (21%) patients. No lead failures or dislocations were observed. Two patients (14%) experienced a complication requiring re-intervention: one infection and one pocket erosion. After the pocket erosion the S-ICD has been successfully re-implanted. In one patient the S-ICD was removed after cardiac transplantation. None of the patients died during follow up. Conclusions: The S-ICD is safe and effective in a diverse pediatric populations. There was a very high efficacy of defibrillation therapy (100%) and a relative low and mild occurrence of complications. The S-ICD should be considered as a viable alternative for transvenous ICD's in pediatric patients.
Emerging mechanisms and novel targets in allergic inflammation and asthma
Authors: Scott T. Weiss
Journal: Genome Medicine (2017)

Airway inflammation is key to the severity and persistence of asthma. Recent studies have revealed novel immune mechanisms that target dendritic cells, T helper 2 cytokines, regulatory T cells, and type 2 innate lymphoid cells in allergic inflammation, as well as novel approaches that target airway smooth muscle in asthma. These advances inform the development of new targeted treatments for allergic inflammation and asthma with the potential to provide therapeutic benefit.
Mortality: a neglected outcome in OCS-treated severe asthma
Authors: Arnaud Bourdin, Nicolas Molinari, Isabelle Vachier, Laurie Pahus, Carey Suehs, Pascal Chanez
Journal: European Respiratory Journal (2017)

Severe asthma, especially if associated with a T2 phenotype, often responds well to new emerging therapies, which have led to a reduction in the use of systemic oral corticosteroids (OCS) [1]. However, OCS-dependent patients still exist and are affected by the well-known (and potentially severe) side effects of such dependency. Longitudinal data that document the outcomes, including death, for these patients are lacking [2]. Here, we present our findings from a long-term severe asthma cohort, which indicate that mortality is a critical issue for these patients. Findings from a long-term severe asthma cohort indicate mortality is a critical issue for OCS-dependent patients <http://ow.ly/rO8e30fZrPo>
Abstract 14298: Basic Cardiovascular Science Best Abstract Award: Allele-specific Disruption Rescues Electrophysiological Abnormalities in Human iPS Cell Model of Long-QT Syndrome With a CALM2 Mutation
Authors: Yuta Yamamoto, Takeru Makiyama, Takeshi Harita, Kenichi Sasaki, Mamoru Hayano, Suguru Nishiuchi, Yimin Wuriyanghai, Hirohiko Kohjitani, Sayako Hirose, Jiarong Chen, Taisuke Ishikawa, Hideki Motomura, Seiko Ohno, Kazuhisa Chonabayashi, Yoshinori Yoshida, Minoru Horie, Naomasa Makita, Takeshi Kimura
Journal: Circulation (2016)

Background: Calmodulin is a ubiquitous Ca2+-sensor molecule and an identical calmodulin protein is encoded by the 3 distinct genes, CALM1-3. Recently, mutations in CALM are reported to be associate...
Exome-wide association study identifies four novel loci for systemic lupus erythematosus in Han Chinese population
Authors: Leilei Wen, Caihong Zhu, Zhengwei Zhu, Chao Yang, Xiaodong Zheng, Lu Liu, Xianbo Zuo, Yujun Sheng, Huayang Tang, Bo Liang, Yi Zhou, Pan Li, Jun Zhu, Yantao Ding, Gang Chen, Jinping Gao, Lili Tang, Yuyan Cheng, Jingying Sun, Tamilselvi Elango, Anjana Kafle, Ruixing Yu, Ke Xue, Yaohua Zhang, Feng Li, Zhanguo Li, Jianping Guo, Xuan Zhang, Chen Zhou, Yuanjia Tang, Nan Shen, Meng Wang, Xueqing Yu, Shengxiu Liu, Xing Fan, Min Gao, Fengli Xiao, Peiguang Wang, Zaixing Wang, Anping Zhang, Fusheng Zhou, Liangdan Sun, Sen Yang, Jinhua Xu, Xianyong Yin, Yong Cui, Xuejun Zhang
Journal: Annals of the Rheumatic Diseases (2017)

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of considerable genetic predisposition. Genome-wide association studies have identified tens of common variants for SLE. However, the majority of them reside in non-coding sequences. The contributions of coding variants have not yet been systematically evaluated.We performed a large-scale exome-wide study in 5004 SLE cases and 8179 healthy controls in a Han Chinese population using a custom exome array, and then genotyped 32 variants with suggestive evidence in an independent cohort of 13 246 samples. We further explored the regulatory effect of one novel non-coding single nucleotide polymorphism (SNP) in ex vivo experiments.We discovered four novel SLE gene regions (LCT, TPCN2, AHNAK2 and TNFRSF13B) encompassing three novel missense variants (XP_016859577.1:p.Asn1639Ser, XP_016859577.1:p.Val219Phe and XP_005267356.1:p.Thr4664Ala) and two non-coding variants (rs10750836 and rs4792801) with genome-wide significance (pmeta <5.00×10-8). These variants are enriched in several chromatin states of primary B cells. The novel intergenic variant rs10750836 exhibited an expression quantitative trait locus effect on the TPCN2 gene in immune cells. Clones containing this novel SNP exhibited gene promoter activity for TPCN2 (P=1.38×10-3) whose expression level was reduced significantly in patients with SLE (P<2.53×10-2) and was suggested to be further modulated by rs10750836 in CD19+ B cells (P=7.57×10-5) in ex vivo experiments.This study identified three novel coding variants and four new susceptibility gene regions for SLE. The results provide insights into the biological mechanism of SLE.
The Ability of Different Imputation Methods to Preserve the Significant Genes and Pathways in Cancer
Authors: Rosa Aghdam, Taban Baghfalaki, Pegah Khosravi, Elnaz Saberi Ansari
Journal: Genomics Proteomics & Bioinformatics (2017)

Abstract Deciphering important genes and pathways from incomplete gene expression data could facilitate a better understanding of cancer. Different imputation methods can be applied to estimate the missing values. In our study, we evaluated various imputation methods for their performance in preserving significant genes and pathways. In the first step, 5% genes are considered in random for two types of ignorable and non-ignorable missingness mechanisms with various missing rates. Next, 10 well-known imputation methods were applied to the complete datasets. The significance analysis of microarrays (SAM) method was applied to detect the significant genes in rectal and lung cancers to showcase the utility of imputation approaches in preserving significant genes. To determine the impact of different imputation methods on the identification of important genes, the chi-squared test was used to compare the proportions of overlaps between significant genes detected from original data and those detected from the imputed datasets. Additionally, the significant genes are tested for their enrichment in important pathways, using the ConsensusPathDB. Our results showed that almost all the significant genes and pathways of the original dataset can be detected in all imputed datasets, indicating that there is no significant difference in the performance of various imputation methods tested. The source code and selected datasets are available on http://profiles.bs.ipm.ir/softwares/imputation_methods/.
Advances in Nanoporous Anodic Alumina‐Based Biosensors to Detect Biomarkers of Clinical Significance: A Review
Authors: Gayathri Rajeev, Beatriz Prieto Simon, Lluis F. Marsal, Nicolas H. Voelcker
Journal: Advanced Healthcare Materials (2017)

Abstract There is a strong and growing demand for compact, portable, rapid, and low‐cost devices to detect biomarkers of interest in clinical and point‐of‐care diagnostics. Such devices aid in early diagnosis of diseases without the need to rely on expensive and time‐consuming large instruments in dedicated laboratories. Over the last decade, numerous biosensors have been developed for detection of a wide range of clinical biomarkers including proteins, nucleic acids, growth factors, and bacterial enzymes. Various transduction techniques have been reported based on biosensor technology that deliver substantial advances in analytical performance, including sensitivity, reproducibility, selectivity, and speed for monitoring a wide range of human health conditions. Nanoporous anodic alumina (NAA) has been used extensively for biosensing applications due to its inherent optical and electrochemical properties, ease of fabrication, large surface area, tunable properties, and high stability in aqueous environment. This review focuses on NAA‐based biosensing systems for detection of clinically significant biomarkers using various detection techniques with the main focus being on electrochemical and optical transduction methods. The review covers an overview of the importance of biosensors for biomarkers detection, general (surface and structural) properties and fabrication of NAA, and NAA‐based biomarker sensing systems.
Metabolic reprogramming of human CD8+ memory T cells through loss of SIRT1
Authors: Mark Y. Jeng, Philip A. Hull, Mingjian Fei, Hye-Sook Kwon, Chia-Lin Tsou, Herb Kasler, Che-Ping Ng, David E. Gordon, Jeffrey Johnson, Nevan Krogan, Eric Verdin, Melanie Ott
Journal: The Journal of Experimental Medicine (2017)

The expansion of CD8+CD28– T cells, a population of terminally differentiated memory T cells, is one of the most consistent immunological changes in humans during aging. CD8+CD28– T cells are highly cytotoxic, and their frequency is linked to many age-related diseases. As they do not accumulate in mice, many of the molecular mechanisms regulating their fate and function remain unclear. In this paper, we find that human CD8+CD28– T cells, under resting conditions, have an enhanced capacity to use glycolysis, a function linked to decreased expression of the NAD+-dependent protein deacetylase SIRT1. Global gene expression profiling identified the transcription factor FoxO1 as a SIRT1 target involved in transcriptional reprogramming of CD8+CD28– T cells. FoxO1 is proteasomally degraded in SIRT1-deficient CD8+CD28– T cells, and inhibiting its activity in resting CD8+CD28+ T cells enhanced glycolytic capacity and granzyme B production as in CD8+CD28– T cells. These data identify the evolutionarily conserved SIRT1–FoxO1 axis as a regulator of resting CD8+ memory T cell metabolism and activity in humans.
Is vitamin D deficiency in breast cancer patients associated with aggressive prognosis?
Authors: Omalkhair A. M. Abulkhair, Ahmed Gasmelseed, Ola Makram, Ahmed Saadeddin, Ahmed Hashim Mohamed
Journal: Journal of Clinical Oncology (2014)

e12511 Background: The role of vitamin D in relation to breast cancer incidence and outcome is controversial. Evidence from observational studies has generally supported an association between higher vitamin D intakes and lower breast cancer risk. We conducted this study to determine serum vitamin D levels in breast cancer patients and to assess its association with breast cancer prognosis. Methods: A cohort prospective study was conducted in KAMC Riyadh oncology department where 406 breast cancer patients were recruited. Serum level of vitamin D was measured four times through the course of the study at the baseline and every 6 months. Results: 87.19% of our patients were Saudi and 99.51% of them were females. Their median age was 48.5 (42-57) years. Of the total cases 41.38% had low deficient levels of vitamin D, 48.03% had levels that were insufficient and only 10.59% had sufficient vitamin D levels. Patients with deficient vitamin D presented in higher proportions with advanced tumor grades (70.83% grade III vs. 52.63% grade I) P-value 0.113, and higher proportions of triple negative breast cancer as well (31.94% triple -ve and 14.19% hormonal +ve) p-value 0.113. Although not statistically significant breast cancer patients with vitamin D deficiency are 2.8 times those with sufficient vitamin D to present with triple negative and 1.9 times to be grade III in comparison to grade I and II (P-values 0.103 and 0.191) respectively. Conclusions: This study has reported only 10% of our breast cancer patients has sufficient vitamin D. The study revealed that vitamin D deficiency might be associated with higher prevalence of advanced tumor grade and triple negative breast cancer as well.
Targeted Microbiome Intervention by Microencapsulated Delayed-Release Niacin Beneficially Affects Insulin Sensitivity in Humans
Authors: Daniela Fangmann, Eva-Maria Theismann, Kathrin Türk, Dominik M. Schulte, Isabelle Relling, Katharina Hartmann, Julia K. Keppler, Jörg-Rainer Knipp, Ateequr Rehman, Femke-Anouska Heinsen, Andre Franke, Lennart Lenk, Sandra Freitag-Wolf, Esther Appel, Stanislav Gorb, Charles Brenner, Dirk Seegert, Georg H. Waetzig, Philip Rosenstiel, Stefan Schreiber, Karin Schwarz, Matthias Laudes
Journal: Diabetes Care (2017)

OBJECTIVE Gut microbiota represent a potential novel target for future prediabetes and type 2 diabetes therapies. In that respect, niacin has been shown to beneficially affect the host-microbiome interaction in rodent models. RESEARCH DESIGN AND METHODS We characterized more than 500 human subjects with different metabolic phenotypes regarding their niacin (nicotinic acid [NA] and nicotinamide [NAM]) status and their gut microbiome. In addition, NA and NAM delayed-release microcapsules were engineered and examined in vitro and in vivo in two human intervention studies (bioavailability study and proof-of-concept/safety study). RESULTS We found a reduced α-diversity and Bacteroidetes abundance in the microbiome of obese human subjects associated with a low dietary niacin intake. We therefore developed delayed-release microcapsules targeting the ileocolonic region to deliver increasing amounts of NA and NAM to the microbiome while preventing systemic resorption to avoid negative side effects (e.g., facial flushing). In vitro studies on these delayed-release microcapsules revealed stable conditions at pH 1.4, 4.5, and 6.8, followed by release of the compounds at pH 7.4, simulating the ileocolonic region. In humans in vivo, gut-targeted delayed-release NA but not NAM produced a significant increase in the abundance of Bacteroidetes. In the absence of systemic side effects, these favorable microbiome changes induced by microencapsulated delayed-release NA were associated with an improvement of biomarkers for systemic insulin sensitivity and metabolic inflammation. CONCLUSION Targeted microbiome intervention by delayed-release NA might represent a future therapeutic option for prediabetes and type 2 diabetes.
10 Minute consultation: Mastering management language syndrome
Authors: David R Warriner, Victoria Twigg, Lucy K Flanders, Edward P Gaynor
Journal: BMJ (2017)

### What you need to know

A 51 year old hospital doctor has been referred to your occupational health clinic. Since a service reorganisation within his local hospital trust, he has been uttering strings of unintelligible jargon such as “paradigm shift,” “granularity,” and “solution focused” punctuated by three letter acronyms such as CCGs, STPs, and ACOs and ending discussions with “What does good look like?” 

A diagnosis of management language syndrome (MLS) …
Patient-Paired Sample Congruence Between 2 Commercial Liquid Biopsy Tests
Authors: Gonzalo Torga, Kenneth J. Pienta
Journal: JAMA Oncology (2017)

Annette S. Kim, MD, PhD; Angela N. Bartley, MD; Julia A. Bridge, MD; Suzanne Kamel-Reid, PhD; Alexander J. Lazar, MD, PhD; Neal I. Lindeman, MD; Thomas A. Long, MPH; Jason D. Merker, MD, PhD; Alex J. Rai, PhD; David L. Rimm, MD, PhD; Paul G. Rothberg, PhD; Patricia Vasalos, BA; Joel T. Moncur, MD, PhD
Abstract A11: A deep learning approach for extracting clinically relevant information from pathology reports
Authors: Waheeda Banu Saib, Pavan Kumar, Geoffrey Siwo, Gciniwe Dlamini, Elvira Singh, Sue Candy, Michael Klipin
Journal: Cancer Research (2017)

Abstract Data-Driven Healthcare, IBM Research Africa, Johannesburg, South Africa The National Cancer Registry (NCR) in South Africa plays a significant role in reporting nationwide cancer statistics and raising the global awareness of the massive impact of cancer. The government requires confirmed cancer cases to be reported to the NCR. Due to manual processes and the increasing magnitude of reports received annually, a considerable lag time exists in cancer statistics, which means the extent of the cancer cases is currently not understood. In addition, the unstructured free-text also needs to be processed in order to identify clinical information that could be important for public health planning. We present initial results from a deep learning approach to address this time lag. Deep learning is a powerful machine-learning algorithm that has made strides in the area of medical image recognition and speech processing. The deep learning system takes as input 2000 de-identified breast cancer pathology reports provided by the NCR in collaboration with the University of Witwatersrand Medical School. The pathology reports are first preprocessed using the Tf-idf (term frequency-inverse document frequency) method, which suggests how important a word is to a document in a corpus by assigning a numerical statistic to each word and hence obtain a term frequency document matrix. The high dimensional data matrix is, input into an unsupervised learning autoencoder, a data compression algorithm used to attain rich features that best represents the specific breast cancer topography and morphology. Unlike other approaches, our approach relies on non-dictionary sources such as clinical empirical knowledge extracted from the reports and dictionary sources such as the 12,000 medical diagnoses available in the International Statistical Classification of Diseases and Related Health Problems (ICD-10). The output from the deep learning system can be used to automate the classification of reports into their corresponding topography and morphology. The system could also be used to create a visual analytics system to aid data exploration and trend analysis of the current state of cancer in South Africa. Citation Format: Waheeda Banu Saib, Pavan Kumar, Geoffrey Siwo, Gciniwe Dlamini, Elvira Singh, Sue Candy, Michael Klipin. A deep learning approach for extracting clinically relevant information from pathology reports [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr A11.