tbuckley/cabot-search huggingface dataset:
Concern of underdiagnosing asthma–COPD overlap syndrome if age limit of 40 years for asthma is used
Authors: Don D. Sin, Janice M. Leung, Michael E. Wechsler
Journal: European Respiratory Journal (2017)

M. Tommola and colleagues raise an important and hotly debated diagnostic criterion of asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS): an age threshold of 40 years for the asthma component of ACOS. We agree with their comment that asthma can develop later in life and these patients may respond well to inhaled corticosteroids and novel biologics, similar to those with childhood-onset asthma [1]. Thus, in the roundtable consensus report [2], we suggested that the asthma component of ACOS could be fulfilled by a clinical diagnosis of asthma before age 40 years or in those without a clinical diagnosis of asthma before 40 years by demonstrating an improvement in forced expiratory volume in 1 s (FEV1) of ≥400 mL following short-acting β2-agonist therapy. While a significant bronchodilatory response (BDR) is a common feature in both asthma and chronic obstructive pulmonary disease (COPD) [3], it is very unusual for COPD patients to demonstrate a BDR of ≥400 mL in FEV1 without a concomitant diagnosis of asthma [4]. To further improve the specificity of the asthma component of ACOS, we also suggested that in addition to all three major criteria, patients fulfil at least one of the three minor criteria: 1) a history of atopy or allergic rhinitis; 2) a BDR of ≥200 mL in FEV1 on two separate visits; or 3) peripheral eosinophil count of ≥300 cells per μL. While none of these criteria has been validated in ACOS, we believe that these criteria are clinically workable and may be useful in identifying patients with asthma with reasonable precision. Future work will be needed to refine these criteria based on high-grade data. While the ACOS criteria have not been validated, they are clinically workable and may identify asthma precisely <http://ow.ly/qLSL30cOh4Z>
VIDEO ANALYSIS OF ACUTE INJURIES IN INTERNATIONAL FIELD HOCKEY
Authors: Udo Rolle, Till-Martin Theilen, Wiebke Müller-Eising, Peter Wefers-Bettink
Journal: British Journal of Sports Medicine (2017)

Background Injury assessment is an essential part of injury prevention, but methods of injury recording vary between different kinds of sport and levels of competition. Objective Analysis of acute injuries in international field hockey tournaments using video footage. Design Retrospective study of acute injuries at international field hockey tournaments. Setting Video footage was assessed and scenes with an acute injury were selected. Acute injury was defined as any new musculoskeletal complaint or concussion, which leads to time stoppage at the game by the umpire. Patients (or Participants) Medical clips were included from the World League 2015 and Champions Trophy 2015 (women, men). Four researchers independently analyzed video footage from 212 matches. Interventions (or Assessment of Risk Factors) The videos were reviewed using a standardized protocol: time of injury/site of injury at the pitch/injury mechanism/injured body part/type of injury/severity of injury. Main Outcome Measurements Incidence and severity of acute injuries, possible rule changes considered. Results Overall number of injuries was 196 in 212 matches (0.92 injuries/match (confidence interval (CI)±0.06)). Number of injuries was 61 in women and 135 in men. This equalled 0.58 injuries/match (CI±0.07) in women and 1.27 injuries/match (CI±0,03) in men. Injuries per 1000 player match hours were 26.2 (CI±3.0) in women; 57.9 (CI±1.5) in men and overall 42.0 (CI±2.6). Most injuries happened within the third quarter and in the circle in both genders. Cause of injury was a hit by the ball or stick or collision with player. Injured body site was mostly head, face, trunk and leg in both genders. Four serious injuries were discovered. Conclusions Video analysis enables accurate assessment of acute field hockey injuries. Video analysis provides detailed information on causes of injuries, which might lead to rule adaptations.
COMPARISON OF THE GLENOID RETROVERSION BY AGE AND POSITION IN ELITE BASEBALL PLAYERS: ASSESSMENT OF 291 ELITE PLAYERS FROM JUNIORS TO PROFESSIONALS
Authors: Jin-Young Park, Jung-Joo Lim
Journal: British Journal of Sports Medicine (2017)

Background In the throwing shoulder, repetitive motion increases proximal humerus and glenoid retroversion. However, clinical factors that affect this adaptation are poorly understood. Objective Evaluate and compare the degree of glenoid retroversion of the throwing and non-throwing shoulders of elite baseball players, and clarify their correlations with clinical factors such as age, position, or period of playing baseball. Design Retrospective study. The subject group in this study consisted of 291 elite baseball players over 13 yrs who visited our clinic for medical check and performed bilateral shoulder three-dimensional computed tomography from December 2011 to December 2014. We reviewed player's hand dominance, age at pitching onset, number of years of playing baseball, position, and demographic data (height, weight). Patients (or Participants) 291 elite baseball players. Players were subdivided into different age groups (juvenile: 13–15, B adolescent: 16–18, youth: 19–25) and their position groups. Methods We measured glenoid version of both throwing and non-throwing shoulders by modified method of Friedman's using developed 3D analysis software. Main Outcome Measurements Each subject underwent three-dimensional (3D) CT, which include bilateral scapulas and proximal humeri. We developed the 3D analysis software to quantitatively measure the glenoid version angle. Results The average glenoid retroversion was significantly larger in the throwing than the non-throwing shoulder. The glenoid retroversion of the non-throwing shoulder became smaller in older age groups (Pearson correlation with age: −0.125; p=0.034). Also, glenoid retroversion of the non-throwing shoulder decreased gradually in proportion to period of playing. The difference between the throwing and non-throwing shoulder became larger in older age groups (correlation with age: 0.121; p=0.039). The difference in retroversion of both shoulders was positively correlated with age and period of playing. Similarly, height and weight also showed significant results (correlation with height: 0.116; p=0.048, with weight: 0.144; p=0.014). But, the glenoid retroversion of throwing shoulder had no statistically significant tendency (p&gt;0.05). There was no difference in glenoid retroversion between different player positions (p&gt;0.05). Conclusions In throwing athletes, glenoid retroversion of the non-throwing shoulder decreased with age, displaying a similar natural course as by normal development. Glenoid retroversion of the throwing shoulder showed no tendency to change and it seems likely that the developmental anteversion course is offset by the retroversion force of the throwing mechanism. The difference between shoulders increases with the age and the duration of the period of playing baseball.
Serendipitous Discovery of Isolated Gastric Metastases From Adenocarcinoma of the Lung on Staging 18F-FDG PET-CT
Authors: Punit Sharma, Amit Dutt Dwary, Enam Murshed Khan
Journal: Clinical Nuclear Medicine (2017)

Gastric metastasis from lung cancer is rare. We here present the case of a 59-year-old man with lung adenocarcinoma where isolated gastric metastases were discovered on staging 18F-FDG PET-CT, confirmed with endoscopy and biopsy.
08.45 The impact of biologic therapies on t cell subsets in rheumatoid arthritis and ankylosing spondylitis: a long term follow-up study
Authors: Sonja Dulic, Zsófia Vásárhelyi, Florentina Sava, László Berta, Balázs Szalay, Gergely Toldi, László Kovács, Attila Balog
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are both characterised by alterations within T-cell subsets. Studies on the impact of biologic therapies, especially of IL6-receptor-antagonists (IL6ra) on this phenotype are limited. We aimed to characterise the T cell repertoire of patients on long-standing biologic treatment and to compare it with that of therapy-naive patients and those with short term anti-TNF treatment. <h3>Materials and methods</h3> We enrolled 92 RA patients, (30 anti-TNF responders, 43 IL6R-antagonist responders and 19 secondary anti-TNF non-responders); and 22 AS patients (15 anti-TNF-responders and 7 non-responders) after at least 6 months of biologic therapies, and 10 healthy controls. The T cell phenotype was assessed with the measurement of 11 cell surface markers with flow cytometry. <h3>Results</h3> In both diseases, patients on long term biologic therapy had decreased proportions of CD4/CD45RA+, CD8CD45RA+ naive T cells and increased frequencies of CD8CD45RO+ memory T cells and Th17 cells. HLA-DR, CD25 and CD69+ activated cell subset prevelences were also increased in certain groups as compared with healthy controls. Treg prevalence has normalised as compared with baseline (before the initiation of biologic therapy) in all patient groups. There were some remarkable differences between IL6ra responders and anti-TNF responders as well (e.g.: Th2, CD69, HLADR prevalence). Most of the changes have become evident only after long-term follow up. In RA, a CD4CD69+ cell percentage &lt;2,43 at baseline predicted a good response to anti-TNF treatment. <h3>Conclusions</h3> Our findings have provided comprehensive information regarding the profound and diverse long term impacts of biological therapies on CD4+ and CD8+ cell distributions in both RA and AS. Although most of the patients had inactive disease, the T cell repertoire after long-standing biological therapy reflects an activated T-cell phenotype. CD4CD69 has been found as a predictive marker of therapeutic response and may help in treatment choice in agreement with the treat-to-target principle in RA.
Protein tyrosine phosphatase 1B deficiency in podocytes mitigates hyperglycemia-induced renal injury
Authors: Yoshihiro Ito, Ming-Fo Hsu, Ahmed Bettaieb, Shinichiro Koike, Aline Mello, Miguel Calvo-Rubio, Jose M. Villalba, Fawaz G. Haj
Journal: Metabolism (2017)
FDG PET/CT in Primary Splenic Angiosarcoma With Diffuse Involvement of the Spleen
Authors: Qian Zhao, Aisheng Dong, Yang Wang, Tianlin He, Changjing Zuo
Journal: Clinical Nuclear Medicine (2017)

Primary splenic angiosarcoma is rare. A 44-year-old man presented with abdominal distension and malaise for 7 months. Laboratory tests showed anemia. Abdominal ultrasound showed enlargement of the spleen with multiple hypoechoic nodules. These nodules showed progressive enhancement on dynamic enhanced CT. Lymphoma was suspected. FDG PET/CT showed increased nonuniform FDG uptake with SUVmax of 11.6 of the entire spleen. Laparoscopic splenectomy was performed. The pathologic findings were consisted with angiosarcoma with replacement of the spleen. Eight months after surgery, multiple hepatic metastases were detected by follow-up abdominal CT.
02.07 Prophylactic treatment with pepitem inhibits onset of collagen induced arthritis and pepitem therapy reduces disease severity
Authors: Samuel Kemble, Adam P Croft, Guillaume Desanti, Atif Saghir, Christopher D Buckley, Helen M McGettrick
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The inappropriate recruitment and retention of T-cells into the joint is a cardinal feature of RA, yet the molecular mechanisms underpinning this remain unclear. We recently showed that patients with Rheumatoid arthritis (RA) have a defect in a newly identified immuno-protective check-point (adiponectin-PEPITEM axis) that normally limits T-cell trafficking during inflammation. Here we examined the therapeutic potential of PEPITEM in a murine model of arthritis. <h3>Methods</h3> Collagen induced arthritis (CIA) was trigger in DBA-1 mice by immunisation with bovine type II collagen. Synthetic PEPITEM was administered by daily injections starting at day 21 (prior to disease onset) or at the first signs of inflammation. Disease onset and severity were evaluated daily. Bone morphology and leukocyte infiltration were assessed by microCT, immunohistochemistry, flow cytometry and qPCR. <h3>Results</h3> Administration of synthetic PEPITEM prior to disease onset inhibited the development of CIA. We observed a significant reduction in disease incidence, clinical score, leukocyte infiltration and bone erosion when compared to control peptide treated mice. Excitingly, PEPITEM therapy administered at the first signs of inflammation in CIA also reduced clinical score, leukocyte infiltration and bone erosion when compared to control mice. Whilst we observed fewer leukocytes in the synovium, PEPITEM therapy did not alter leukocyte trafficking through the draining lymph node. Interestingly, in both approaches, we detected higher levels of the FOXP3 transcript, and T<sub>Reg</sub> cells, in PEPITEM treated mice than in control animals. <h3>Conclusions</h3> This leads to the exciting possibility that targeting PEPTIEM represents a valid therapeutic approach for treating T-cell mediated diseases, such as RA. <h3>Funding</h3> This work was funded by a Pfizer I-CRP research grant.
Large joint involvement at first presentation with RA, an unfavourable feature: results of a large longitudinal study with functioning and DMARD-free sustained remission as outcomes
Authors: Leonie E Burgers, Debbie M Boeters, Annette HM van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2017)

With great interest we read the recently published letter by Rubbert-Roth et al .1 In a post-hoc analysis of the U-Act-Early trial in 317 patients with very early rheumatoid arthritis (RA),2 it was observed that patients with large joint involvement (LJI) at baseline had significantly more disease activity and more functional disability at baseline. In addition, while the disease activity score (DAS) was similar after 2 years of follow-up compared with patients without LJI, the difference in functional disability remained. Furthermore, patients without LJI had a higher chance of achieving drug-free remission. The authors concluded that equal weighting of joints in the DAS is contrasting an unequal impact on physical function.1 

The idea of a weighted joint score is not new. A joint index that takes the joint surface into account, thus weighing large joints heavier than small joints, is the Lansbury index.3 It has been reported that this index correlates better with C reactive protein (CRP) than joint …
Skin signs of primary immunodeficiencies: how to find the genes to check
Authors: M. Ettinger, J. Schreml, K. Wirsching, M. Berneburg, S. Schreml
Journal: British Journal of Dermatology (2017)

Primary immunodeficiencies (PIDs) are a heterogeneous group of rare diseases that result from defects in immune system development and/or function. The clinical manifestations of PIDs are highly variable, but most disorders involve at least an increased susceptibility to infection. Furthermore, cutaneous manifestations are very common in PIDs. As an easily accessible organ, the skin can be crucial for early diagnosis and treatment. This is relevant for preventing significant disease-associated morbidity and mortality. We provide a table that enables the reader to find the possible diseases and corresponding gene defects based on the skin manifestations of the suspected PIDs. To our knowledge, this is the first review that allows the reader to find relevant PIDs and the respective gene defects through solitary or combined skin signs.
骨様アパタイトの蛋白質形成:炭酸化の重要な役割への新たな洞察【Powered by NICT】
Authors: C Deymier Alix, K Nair Arun, Depalle Baptiste, Qin Zhao, Arcot Kashyap, Drouet Christophe, H Yoder Claude, J Buehler Markus, Thomopoulos Stavros, M Genin Guy, D Pasteris Jill
Journal: Biomaterials (2017)
Abstract 16466: Comparison of Cardiac Engraftment With Two Catheter-Based Delivery Methods: Catheter-Mediated Intramyocardial Delivery Outperforms Intracoronary Delivery of Cardiosphere-Derived Cells in Porcine Ischemic Cardiomyopahty
Authors: Hideaki Kanazawa, Konstantinos Malliaras, Kristine Yee, Eleni Tseliou, Linda Marban, Rajendra Makkar, Eduardo Marban
Journal: Circulation (2011)

Background: Dosage-optimized intracoronary (IC) and direct intramyocardial (IM) delivery of cardiosphere-derived cells (CDCs) have both been demonstrated to be safe and effective in porcine ischemi...
Respiratory syncytial virus infections in Croatia, 1994-99
Authors: Amarela Lukić-Grlić, Gordana Mlinarić-Galinović, Vladimir Draženović, A Barišin, Ana Baće, Vilka Hrešić-Kršulović, Renata Sim, B Berberović, E Berberović
Journal: Clinical Microbiology and Infection (2005)
Tissue Engineering: Rod‐Shaped Neural Units for Aligned 3D Neural Network Connection (Adv. Healthcare Mater. 15/2017)
Authors: Midori Kato‐Negishi, Hiroaki Onoe, Akane Ito, Shoji Takeuchi
Journal: Advanced Healthcare Materials (2017)

The cover shows a three-dimensional (3D) neural network formed by rod-shaped neural units, which are 3D fiber-shaped neural tissues with aligned nerve fibers, to connect neural networks with aligned neurons. Neural networks can be formed between the different neural units via synaptic connections as described by Shoji Takeuchi and co-workers in article number 1700143.
肝疾患:Tmbim1は多胞体調節因子であり,リソソームでのTlr4の分解を標的としてマウスやサルの非アルコール性脂肪性肝の発症を防止する
Authors: Zhao Guang‐Nian, Zhang Peng, JI Yan‐Xiao, LI Hongliang, Gong Jun, Zhang Xiao‐Jing, Wang Pi‐Xiao, Yin Miao, Jiang Zhou, Shen Li‐Jun, Tong Jingjing, Wang Yutao, Wei Qiao‐Fang, Zhu Xue‐Yong, Zhang Xin, She Zhi‐Gang, Wang Zhihua, Huang Zan, Wang Yong, Fang Jing, Xie Qingguo
Journal: Nature Medicine (2017)
Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer
Authors: Delphine Merino, James R. Whittle, François Vaillant, Antonin Serrano, Jia-Nan Gong, Goknur Giner, Ana Leticia Maragno, Maïa Chanrion, Emilie Schneider, Bhupinder Pal, Xiang Li, Grant Dewson, Julius Gräsel, Kevin Liu, Najoua Lalaoui, David Segal, Marco J. Herold, David C. S. Huang, Gordon K. Smyth, Olivier Geneste, Guillaume Lessene, Jane E. Visvader, Geoffrey J. Lindeman
Journal: Science Translational Medicine (2017)

The development of BH3 mimetics, which antagonize prosurvival proteins of the BCL-2 family, represents a potential breakthrough in cancer therapy. Targeting the prosurvival member MCL-1 has been an area of intense interest because it is frequently deregulated in cancer. In breast cancer, MCL-1 is often amplified, and high expression predicts poor patient outcome. We tested the MCL-1 inhibitor S63845 in breast cancer cell lines and patient-derived xenografts with high expression of MCL-1. S63845 displayed synergistic activity with docetaxel in triple-negative breast cancer and with trastuzumab or lapatinib in HER2-amplified breast cancer. Using S63845-resistant cells combined with CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated 9) technology, we identified deletion of BAK and up-regulation of prosurvival proteins as potential mechanisms that confer resistance to S63845 in breast cancer. Collectively, our findings provide a strong rationale for the clinical evaluation of MCL-1 inhibitors in breast cancer.
Adaptive cell plasticity in autocrine TGFβ2 coordinated transcriptome-metabolome reprogramming of EGFR-mutant lung cancer in precision therapy escape.
Authors: Patrick C. Ma, Praveena Thiagarajan, Patrick Leahy, Rakesh K. Bagai, Ivy Shi, Wei Zhang, Yan Feng, Martina L Veigl, Daniel Lindner, David Danielpour, Lihong Yin, Rafael Rosell, Trever Grant Bivona
Journal: Journal of Clinical Oncology (2014)

e19043 Background: Precision therapy for advanced NSCLC with EGFR mutations is the current standard-of-care. Emergence of acquired resistance to therapy invariably occurs despite effective initial response. Classical rebiopsy studies of EGFR-mutant pts at progression have identified diverse resistance mechanisms involving T790M-EGFR, METactivation and AXL upregulation. Our studies focus on tumor cells adaptation early during therapy to map the initial course of therapeutic resistance evolution. Methods: Drug-sensitive model studies were performed usingHCC827 and PC-9 NSCLC cells under erlotinib, and H1975 cells under CL-387,785 inhibition. Affymetrix microarray profiling was performed at 0h, 8h, 9d and 9d TKI followed by 7d drug-washout. Both in vitro and in vivo xenograft analyses were conducted. Mass-spectrometry based metabolomics profiling was also conducted. Results: We identified an early adaptive drug escape in EGFR-mutant cells that emerged as early as 9 days on therapy. The prosurvival cell state was MET-independent with a TKI cytotoxicity escape at 100x higher IC50. Transcriptome profiling revealed a remarkable genome-wide signature adaptive reprogramming, centered on the autocrine TGFβ2 cascade, involving pathways of cell adhesion, cell cycle regulation, cell division, glycolysis, and gluconeogenesis. Corroborating the transcriptome profiling results, metabolomic profiling also revealed an adaptive metabolic reprogramming with suppression of glycolysis, TCA cycle, amino acids metabolism, and lipid bioenergetics during drug escape. Our studies identified a direct link of TGFβ2 within the early adaptive drug escaping cells, with the metabolic-bioenergetics quiescence and mitochondrial BCL-2/BCL-xL priming. Furthermore, this state of cellular plasticity displayed an increased EMT and cancer stem cell signaling as adaptation to the drug treatment and that could be overcome by dual BCL2/BCL-xL BH3 mimetics. Conclusions: We have identified and characterized a cellular plasticity state in early adaptivedrug escaping EGFR-mutant NSCLC cells undergoing remarkable cellular reprogramming, with therapeutic implications.
Comment on CONCEPT by Reginster <i>et al</i>: are the authors’ interpretations supported by the data analysis?
Authors: Sinan Kardeş
Journal: Annals of the Rheumatic Diseases (2017)

I read with great interest the ChONdroitin versus CElecoxib versus Placebo Trial (CONCEPT) by Reginster et al. 1 I would like to raise some worthwhile issues that need to be clarified.

The authors concluded that 800 mg/day pharmaceutical-grade chondroitin sulfate (CS) is similar to celecoxib in improving pain and function after 6 months in patients with symptomatic knee osteoarthritis (OA).1 However, the interpretation of similarity between these two active treatments was not based on the analysis of the data. Because, the authors did not assess whether these treatments are similar by equivalence analysis. Rather, the authors assessed the superiority between these two active treatments by aiming to detect a difference in intention-to-treat (ITT) populations—although the study might not be powered to be able to detect differences between these two active treatments (type 2 error), since sample size is calculated to show superiority of CS over placebo; and they failed to show a difference between CS and celecoxib. According to the Consolidated Standards of Reporting Trials 2010 statement on reporting of non-inferiority and equivalence randomised trials, ’Failure to show a difference does not mean they are equivalent. By contrast, …