bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful Cholecystectomy After Endoscopic Ultrasound Gallbladder Drainage Compared With Percutaneous Cholecystostomy, Can it Be Done?
Authors: Saumoy Monica , Tyberg Amy , Brown Elizabeth , Eachempati Soumitra R. , Lieberman Michael , Afaneh Cheguevara , Kunda Rastislav , Cosgrove Natalie , Siddiqui Ali , Gaidhane Monica , Kahaleh Michel 
Published: April 2018

Background:
Endoscopic ultrasound–guided gallbladder drainage (EGBD) with a lumen apposing metal stent is becoming a widely accepted alternative to percutaneous gallbladder drainage (PTGD) for patients who are not candidates for cholecystectomy (CCY). In some patients, medical comorbidites can improve, allowing them to undergo CCY. We compare feasibility and outcomes of interval CCY after EGBD versus PTGD.

Methods:
We conducted a multicentered international cohort study of patients who underwent EGBD or PTGD and then underwent interval CCY. Baseline patient demographics, procedural details, and follow-up data were recorded and compared.

Results:
In total, 34 patients were included. Thirteen patients underwent EGBD followed by CCY (mean age, 53.77±17.27, 46.15% male), and 21 patients underwent PTGD followed by CCY (mean age, 62.14±13.06, 61.9% male). There was no statistically significant difference in mean Charlson Comorbidity Index (P=0.12) or etiology of cholecystitis (P=0.85) between the 2 groups. All patients had a technically successful CCY. There was no difference between rates of open versus laparoscopic CCY (P=1). In addition, there was no difference in postsurgical adverse events (P=0.23).

Conclusions:
Surgical CCY after EGBD with lumen apposing metal stent is safe and feasible for the management of cholecystitis. If patient’s underlying medical conditions improve, previous EUS-GLB drainage should not preclude patients from undergoing CCY as part of standard of care.
Large Volume Fluid Resuscitation for Severe Acute Pancreatitis is Associated With Reduced Mortality
Authors: Yamashita Takahiro , Horibe Masayasu , Sanui Masamitsu , Sasaki Mitsuhito , Sawano Hirotaka , Goto Takashi , Ikeura Tsukasa , Hamada Tsuyoshi , Oda Takuya , Yasuda Hideto , Ogura Yuki , Miyazaki Dai , Hirose Kaoru , Kitamura Katsuya , Chiba Nobutaka , Ozaki Tetsu , Koinuma Toshitaka , Oshima Taku , Yamamoto Tomonori , Hirota Morihisa , Masuda Yukiko , Tokuhira Natsuko , Kobayashi Mioko , Saito Shinjiro , Izai Junko , Lefor Alan K. , Iwasaki Eisuke , Kanai Takanori , Mayumi Toshihiko 
Published: April 2018

Background and Aims:Although fluid resuscitation is critical in acute pancreatitis, the optimal fluid volume is unknown. The aim of this study is to evaluate the association between the volume of fluid administered and clinical outcomes in patients with severe acute pancreatitis (SAP).Methods:We conducted a multicenter retrospective study at 44 institutions in Japan. Inclusion criteria were age 18 years or older, and diagnosed with SAP from 2009 to 2013. Patients were stratified into 2 groups: administered fluid volume <6000 and ≥6000 mL in the first 24 hours. We evaluated the association between the 2 groups and clinical outcomes using multivariable logistic regression analysis. The primary outcome was in-hospital mortality. Secondary outcomes included the incidence of pancreatic infection and the need for surgical intervention.Results:We analyzed 1097 patients, and the mean fluid volume administered was 5618±3018 mL (mean±SD), with 708 and 389 patients stratified into the fluid <6000 mL and fluid ≥6000 mL groups, respectively. Overall in-hospital mortality was 12.3%. The fluid ≥6000 mL group had significantly higher mortality than the fluid <6000 mL group (univariable analysis, 15.9% vs. 10.3%;P<0.05). In multivariable logistic regression analysis, administration of ≥6000 mL of fluid within the first 24 hours was significantly associated with reduced mortality (odds ratio, 0.58;P<0.05). No significant association was found between the administered fluid volume and pancreatic infection, or between the volume administered and the need for surgical intervention.Conclusions:In patients with SAP, administration of a large fluid volume within the first 24 hours is associated with decreased mortality.
Association of clinical and inflammatory markers with small bowel capsule endoscopy findings in Crohn’s disease
Authors: Mitselos Ioannis V. , Katsanos Konstantinos H. , Tatsioni Athina , Skamnelos Alexandros , Eliakim Rami , Tsianos Epameinondas V. , Christodoulou Dimitrios K. 
Published: April 2018

Background
Mucosal healing is an established treatment endpoint in Crohn’s disease (CD). Still, clinical indices and inflammatory markers are used widely in CD surveillance.

Aim
The aim of this study was to investigate the diagnostic performance as well as the relationship of C-reactive protein (CRP) and Crohn’s Disease Activity Index (CDAI) with small bowel capsule endoscopy’s (SBCE) inflammation scoring index, the Lewis Score (LS).

Patients and methods
CDAI, CRP, and SBCE findings of 30 CD patients with isolated small bowel disease were retrieved from our academic institution patient records and were analyzed statistically.

Results
SBCE showed significant mucosal inflammation [mean (SD) LS: 1599 (1380)], in nine (60.0%) of 15 patients who were in both clinical and biochemical remission. CDAI and CRP showed a weak and moderate correlation with LS (r=0.317, P=0.088 and r=0.516, P=0.004, respectively). The diagnostic performance of CDAI and CRP in predicting mucosal inflammation was as follows: sensitivity 23.8 and 52.4%; specificity 100 and 66.7%; positive predictive value 100 and 78.6%; and negative predictive value 36.0 and 37.5%. The area under the curve toward endoscopic activity prediction was 0.70 and 0.69, respectively.

Conclusion
Both CDAI and CRP underestimated endoscopic activity as expressed by the LS in a significant proportion of patients with quiescent disease.
Cohesin in haematopoiesis and leukaemia
Authors: Galeev Roman , Larsson Jonas 
Published: April 2018

Purpose of review
Disturbance of the delicate balance between self-renewal and differentiation in haematopoietic stem cells (HSCs) can lead to both leukaemia and bone marrow failure. The regulation of this balance in HSC biology has been intensely investigated in several model systems, and lately the importance of epigenetic modifications as well as the organization and architecture of chromatin has become increasingly recognized. In this review, we will focus on the role of the chromatin organizing protein complex cohesin in regulation of normal and malignant haematopoiesis.

Recent findings
Several functional studies in both mouse and human systems have implicated cohesin as a critical regulator of self-renewal and differentiation in HSCs. Together with the discovery of recurrent mutations of cohesin genes in myeloid malignancies, this points towards a direct role of perturbed cohesin function in leukemogenesis.

Summary
The work reviewed here provides new insights about the role of the cohesin complex and chromatin architecture in normal and malignant HSCs, and indicates how cohesin may be specifically targeted for therapeutic benefit in the future.
Reduction in Blood Glutamate Levels Combined With the Genetic Inactivation of A2AR Significantly Alleviate Traumatic Brain Injury-Induced Acute Lung Injury
Authors: Bai Wei , Li Ping , Ning Ya-Lei , Jiang Yu-Lin , Yang Nan , Chen Xing , Zhou Yuan-Guo 
Published: April 2018

ABSTRACT
Traumatic brain injury-induced acute lung injury (TBI-ALI) is a serious complication of traumatic brain injury (TBI). Our previous clinical study found that high levels of blood glutamate after TBI were closely related to the occurrence and severity of TBI-ALI, while it remains unknown whether a high concentration of blood glutamate directly causes or aggravates TBI-ALI. We found that inhibition of the adenosine A2A receptor (A2AR) after brain injury alleviated the TBI-ALI; however, it is unknown whether lowering blood glutamate levels in combination with inhibiting the A2AR would lead to better effects. Using mouse models of moderate and severe TBI, we found that intravenous administration of L-glutamate greatly increased the lung water content, lung-body index, level of inflammatory markers in bronchoalveolar lavage fluid and acute lung injury score and significantly decreased the PaO2/FiO2 ratio. Moreover, the incidence of TBI-ALI and the mortality rate were significantly increased, and the combined administration of A2AR activator and exogenous glutamate further exacerbated the above damaging effects. Conversely, lowering the blood glutamate level through peritoneal dialysis or intravenous administration of oxaloacetate notably improved the above parameters, and a further improvement was seen with concurrent A2AR genetic inactivation. These data suggest that A2AR activation aggravates the damaging effect of high blood glutamate concentrations on the lung and that combined treatment targeting both A2AR and blood glutamate may be an effective way to prevent and treat TBI-ALI.
Objective Evidence of Reflux Control After Magnetic Sphincter Augmentation
Authors: Louie Brian E. , Smith C. Daniel , Smith Christopher C. , Bell Reginald C. W. , Gillian George Kevin , Mandel Jeffrey S. , Perry Kyle A. , Birkenhagen Walter Kurt , Taiganides Paul A. , Dunst Christy M. , McCollister Howard M. , Lipham John C. , Khaitan Leena K. , Tsuda Shawn T. , Jobe Blair A. , Kothari Shanu N. , Gould Jon C. 
Published: April 2018

Objective:
To report 1-year results from a 5-year mandated study.

Summary Background Data:
In 2012, the United States Food and Drug Administration approved magnetic sphincter augmentation (MSA) with the LINX Reflux Management System (Torax Medical, Shoreview, MN), a novel device for the surgical treatment of gastroesophageal reflux disease (GERD). Continued assessment of safety and effectiveness has been monitored in a Post Approval Study.

Methods:
Multicenter, prospective study of patients with pathologic acid reflux confirmed by esophageal pH testing undergoing MSA. Predefined clinical outcomes were assessed at the annual visit including a validated, disease-specific questionnaire, esophagogastricduodenoscopy and esophageal pH monitoring, and use of proton pump inhibitors.

Results:
A total of 200 patients (102 males, 98 females) with a mean age of 48.5 years (range 19.7–71.6) were treated with MSA between March 2013 and August 2015. At 1 year, the mean total acid exposure time decreased from 10.0% at baseline to 3.6%, and 74.4% of patients had normal esophageal acid exposure time (% time pH<4 ≤5.3%). GERD Health-Related Quality of Life scores improved from a median score of 26.0 at baseline to 4.0 at 1 year, with 84% of patients meeting the predefined success criteria of at least a 50% reduction in total GERD Health-Related Quality of Life score compared with baseline. The device removal rate at 1 year was 2.5%. One erosion and no serious adverse events were reported.

Conclusions:
Safety and effectiveness of magnetic sphincter augmentation has been demonstrated outside of an investigational setting to further confirm MSA as treatment for GERD.
No Surgical Innovation Without Evaluation
Authors: Hirst Allison , Philippou Yiannis , Blazeby Jane , Campbell Bruce , Campbell Marion , Feinberg Joshua , Rovers Maroeska , Blencowe Natalie , Pennell Christopher , Quinn Tom , Rogers Wendy , Cook Jonathan , Kolias Angelos G. , Agha Riaz , Dahm Philipp , Sedrakyan Art , McCulloch Peter 
Published: April 2018

Objective:
To update, clarify, and extend IDEAL concepts and recommendations.

Background:
New surgical procedures, devices, and other complex interventions need robust evaluation for safety, efficacy, and effectiveness. Unlike new medicines, there is no internationally agreed evaluation pathway for generating and analyzing data throughout the life cycle of surgical innovations. The IDEAL Framework and Recommendations were designed to provide this pathway and they have been used increasingly since their introduction in 2009. Based on a Delphi survey, expert workshop and major discussions during IDEAL conferences held in Oxford (2016) and New York (2017), this article updates and extends the IDEAL Recommendations, identifies areas for future research, and discusses the ethical problems faced by investigators at each IDEAL stage.

Methods:
The IDEAL Framework describes 5 stages of evolution for new surgical therapeutic interventions—Idea, Development, Exploration, Assessment, and Long-term Study. This comprehensive update proposes several modifications. First, a “Pre-IDEAL” stage describing preclinical studies has been added. Second we discuss potential adaptations to expand the scope of IDEAL (originally designed for surgical procedures) to accommodate therapeutic devices, through an IDEAL-D variant. Third, we explicitly recognise the value of comprehensive data collection through registries at all stages in the Framework and fourth, we examine the ethical issues that arise at each stage of IDEAL and underpin the recommendations. The Recommendations for each stage are reviewed, clarified and additional detail added.

Conclusions:
The intention of this article is to widen the practical use of IDEAL by clarifying the rationale for and practical details of the Recommendations. Additional research based on the experience of implementing these Recommendations is needed to further improve them.
Modified Blumgart Mattress Suture Versus Conventional Interrupted Suture in Pancreaticojejunostomy During Pancreaticoduodenectomy
Authors: Hirono Seiko , Kawai Manabu , Okada Ken-Ichi , Miyazawa Motoki , Kitahata Yuji , Hayami Shinya , Ueno Masaki , Yamaue Hiroki 
Published: April 2018

Objective:
This study used a randomized controlled trial (RCT) to evaluate whether mattress suture of pancreatic parenchyma and the seromuscular layer of jejunum (modified Blumgart method) during pancreaticojejunostomy (PJ) decreases the incidence of clinically relevant postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD).

Background:
Several studies reported that mattress suture of Blumgart anastomosis in PJ could reduce POPF rate. This, however, is the first RCT.

Methods:
Between June, 2013 and May, 2017, 224 patients scheduled for PD were enrolled in this study in Wakayama Medical University Hospital. Enrolled patients were randomized to either interrupted suture or modified Blumgart mattress suture. The primary endpoint was the incidence of grade B/C POPF based on the International Study Group on Pancreatic Fistula criteria. This RCT was registered with ClinicalTrials.gov (NCT01898780).

Results:
Patients were randomized to either interrupted suture (103 patients) or modified Blumgart mattress suture (107 patients) and were analyzed by intention-to-treat. Grade B/C POPF occurred in 7 patients (6.8%) in the interrupted suture group and 11 (10.3%) in the mattress suture group (P = 0.367). Mortality within 90 days was 0 in both groups. There were no significant differences in all postoperative complications between the interrupted suture group and the modified Blumgart mattress suture group.

Conclusions:
Mattress suture of pancreatic parenchyma and the jejunal seromuscular layer during PJ (modified Blumgart technique) did not reduce clinically relevant POPF compared with interrupted suture.
Self-organization: the fundament of cell biology
Authors: Wedlich-Söldner Roland , Betz Timo 
Published: April 2018

Self-organization refers to the emergence of an overall order in time and space of a given system that results from the collective interactions of its individual components. This concept has been widely recognized as a core principle in pattern formation for multi-component systems of the physical, chemical and biological world. It can be distinguished from self-assembly by the constant input of energy required to maintain order—and self-organization therefore typically occurs in non-equilibrium or dissipative systems. Cells, with their constant energy consumption and myriads of local interactions between distinct proteins, lipids, carbohydrates and nucleic acids, represent the perfect playground for self-organization. It therefore comes as no surprise that many properties and features of self-organized systems, such as spontaneous formation of patterns, nonlinear coupling of reactions, bi-stable switches, waves and oscillations, are found in all aspects of modern cell biology. Ultimately, self-organization lies at the heart of the robustness and adaptability found in cellular and organismal organization, and hence constitutes a fundamental basis for natural selection and evolution.
This article is part of the theme issue ‘Self-organization in cell biology’.
Autotransporter secretion exploits the bacterial actin-homologue
Authors: Ashawesh Mahmoud M. , Markus Robert , Penfold Christopher N. , Hardie Kim R. 
Published: April 2018

AbstractBacterial infection of humans, animals and plants relies heavily on secreted proteases that degrade host defences or activate bacterial toxins. The largest family of proteins secreted by Gram-negative pathogenic bacteria, the Autotransporters (ATs), includes key proteolytic virulence factors. There remains uncertainty about the mechanistic steps of the pathway ATs share to exit bacteria, and how it is energetically driven. This study set out to shed light on the AT secretion pathway with the ultimate aim of uncovering novel antimicrobial targets that would be unlikely to trigger the development of resistance mechanisms in bacteria. To do this, two AT virulence factors with distinct proteolytic functions, EspC (secreted from EnteropathogenicEscherichia coli) and AaaA (tethered to the extracellular surface ofPseudomonas aeruginosa) were chosen. EspC and AaaA were fluorescently labelled using two separate methods to establish the localization patterns of ATs as they are secreted from a bacterial cell. Super resolution microscopy revealed that localization of ATs occurs via a helical route along the bacterial cytoskeleton. In addition to requiring the conserved C-terminal β-barrel translocator domain of the AT, we present the first evidence that secretion is dependent on a dynamic interaction with a structure reliant upon the actin homologue MreB and the Sec translocon. These findings provide a step forward in the mechanistic understanding of the secretion of this widely distributed family of proteins that have pivotal roles in bacterial pathogenesis and conserved structural properties that could serve as novel broad-range antimicrobial targets.SignificanceSecreted bacterial proteases facilitate the infection of human, animal and plant hosts by degrading host defences or activating bacterial toxins. The autotransporter family is the largest family of proteins secreted from Gram-negative bacteria, and includes proteolytic virulence factors crucial to bacterial infection. Precisely how autotransporters migrate from the inside to the outside of the cell, and how this movement is energetically driven is a mystery. We demonstrate a spiral pathway of autotransporter secretion, presenting evidence that it involves a dynamic interaction with the actin homologue MreB that comprises the bacterial cytoskeleton. Our findings open the way to unravelling the mechanism of autotransporter secretion and offer the possibility to identify novel antimicrobial targets unlikely to trigger the development of antimicrobial resistance.
Modulation of Secretory Lysosomes During NK Cell Education Leads to Accumulation of Granzyme B and Enhanced Functional Potential
Authors: Goodridge Jodie P. , Jacobs Benedikt , Saetersmoen Michelle L. , Clement Dennis , Clancy Trevor , Skarpen Ellen , Brech Andreas , Landskron Johannes , Grimm Christian , Pfefferle Aline , Meza-Zepeda Leonardo , Lorenz Susanne , Wiiger Merete Thune , Louch William E. , Ask Eivind Heggernes , Liu Lisa L. , Sheng Oei Vincent Yi , Kjällquist Una , Linnarsson Sten , Patel Sandip , Taskén Kjetil , Stenmark Harald , Malmberg Karl-Johan 
Published: April 2018

AbstractInhibitory signaling during natural killer (NK) cell education translates into increased responsiveness to activation; however the intracellular mechanism for functional tuning by inhibitory receptors remains unclear. We found that educated NK cells expressing self-MHC specific inhibitory killer cell immunoglobulin-like receptors (KIR) show accumulation of granzyme B, localized in dense-core secretory lysosomes, converged close to the centrosome. This discrete morphological phenotype persists in self-KIR+NK cells independently of transcriptional programs that regulate effector function, metabolism and lysosomal biogenesis. The granzymeB dense, large secretory lysosomes in self-KIR+NK cells were efficiently released upon target cell recognition, contributing to their enhanced cytotoxic capacity. Secretory lysosomes are part of the acidic lysosomal compartment, which has been shown to channel calcium and mediate intracellular signalling in several cell types. Interference of signaling from acidic Ca2+stores in primary NK cells reduced both target-specific Ca2+-flux, degranulation and cytokine production. Furthermore, inhibition of PI(3,5)P2synthesis or genetic silencing of the PI(3,5)P2-regulated lysosomal Ca2+-channel TRPML1 led to increased levels of granzyme B and enhanced functional potential. These results indicate an intrinsic role for lysosomal homeostasis in NK cell education.
A common statistical misunderstanding in Psychology and Neuroscience: Do we need normally distributed independent or dependent variables for linear regression to work?
Authors: Habeck Christian G. , Brickman Adam M. 
Published: April 2018

AbstractOur ability to draw conclusions from experiments often relies on the application of inferential statistics, such as those included within the general-linear-modeling framework. The purpose of this commentary is to direct attention a common fallacy that can be observed in paper reviews and professional exchanges in the field of Psychology and Neuroscience pertaining to multiple regression analysis. The fallacy concerns the confusion of the requirements on theresidualsof a linear-regression model with requirements on thedependent or independent variablesthemselves. A simple thought experiment, algebraic demonstration, and simulation study can demonstrate this misconception. It is our hope that consideration of the fallacy may help clarify distinctions between technical statistical issues and conceptual interpretation of research findings.
Geometric morphometrics of nested symmetries: Hierarchical INTER- AND INTRA-INDIVIDUAL VARIATION IN BIOLOGICAL SHAPES
Authors: Savriama Yoland , Gerber Sylvain 
Published: April 2018

AbstractSymmetry is a pervasive feature of organismal shape and the focus of a large body of research in Biology. Here, we consider complex patterns of symmetry where a phenotype exhibits a hierarchically structured combination of symmetries. We extend the Procrustes ANOVA for the analysis of nested symmetries and the decomposition of the overall morphological variation into components of symmetry (among-individual variation) and asymmetry (directional and fluctuating asymmetry). We illustrate its use with the Aristotle’s lantern, the masticatory apparatus of ‘regular’ sea urchins, a complex organ displaying bilateral symmetry nested within five-fold rotational symmetry. Our results highlight the importance of characterising the full symmetry of a structure with nested symmetries. Higher order rotational symmetry appears strongly constrained and developmentally stable compared to lower level bilateral symmetry. This contrast between higher and lower levels of asymmetry is discussed in relation to the spatial pattern of the lantern morphogenesis. This extended framework is applicable to any biological object exhibiting nested symmetries, regardless of their type (e.g., bilateral, rotational, translational). Such cases are extremely widespread in animals and plants, from arthropod segmentation to angiosperm inflorescence and corolla shape. The method therefore widens the research scope on developmental instability, canalization, developmental modularity and morphological integration.