bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gadolinium-Based Contrast Agent During Pelvic MRI: Contribution to Patient Management in Rectal Cancer
Authors: Corines Marina J. , Nougaret Stephanie , Weiser Martin R. , Khan Monika , Gollub Marc J. 
Published: January 2018

BACKGROUND:
Few publications exist regarding gadolinium-enhanced sequences in rectal MRI. None have evaluated its potential impact on patient management.

OBJECTIVE:
This study aimed to assess whether gadolinium-enhanced sequences, including dynamic contrast enhancement, change radiologic interpretation and clinical management of rectal cancer.

DESIGN:
This is a retrospective analysis of 100 rectal MRIs (50 baseline and 50 postneoadjuvant treatment), both without and with gadolinium-enhanced sequences. Treatment plans were rendered based on each radiologic interpretation for each case by a single experienced surgeon. Differences in radiologic interpretation and management were statistically analyzed.

SETTINGS:
The study was conducted at the Memorial Sloan Kettering Cancer Center.

PATIENTS:
Patients undergoing rectal MRI between 2011 and 2015 for baseline tumor staging and/or postneoadjuvant restaging were included.

MAIN OUTCOME MEASURES:
Primary outcome measures were changes in radiologic tumor stage, tumor margins, and surgical planning with the use of gadolinium at baseline and postneoadjuvant time points.

RESULTS:
At baseline, tumor downstaging occurred in 8 (16%) of 50 and upstaging in 4 (8%) of 50 with gadolinium. Postneoadjuvant treatment, upstaging occurred in 1 (2%) of 50 from T2 to T3a. At baseline, mean distances from tumor to anorectal ring, anal verge, and mesorectal fascia were not statistically different with gadolinium. However, in 7 patients, differences could have resulted in treatment changes, accounted for by changes in relationships to anterior peritoneal reflection (n = 4), anorectal ring (n = 2), or anal verge (n = 1). Postneoadjuvant treatment, distances to anorectal ring and anal verge (in centimeters) were statistically smaller with gadolinium (p = 0.0017 and p = 0.0151) but could not have resulted in clinically significant treatment changes.

LIMITATIONS:
This study was limited by its retrospective design.

CONCLUSIONS:
The use of gadolinium at baseline MRI could have altered treatment in 24% of patients because of differences in tumor stage or position. Postneoadjuvant treatment, gadolinium resulted in statistically smaller distances to sphincters, which could influence surgical decision for sphincter-preserving rectal resection. See Video Abstract at http://links.lww.com/DCR/A444.
Lémann Index at Diagnosis Predicts the Risk of Early Surgery in Crohn’s Disease
Authors: Liu Wei , Zhou Wei , Xiang Jianjian , Cao Qian , Zhu Jinzhou , Qi Weilin , Chen Pengpeng , Xie Qingwen 
Published: January 2018

BACKGROUND:
Identifying patients with Crohn’s disease with rapid disease progress or high risk of early surgery is crucial to clinical decision making.

OBJECTIVE:
The aim was to evaluate the correlation between the Lémann index at diagnosis and abdominal surgery in the first year after Crohn’s disease diagnosis and to find the risk factors for early surgery.

DESIGN:
This was a retrospective cohort study.

SETTINGS:
The study was conducted at a single tertiary hospital.

PATIENTS:
Patients diagnosed with Crohn’s disease between 2013 and 2015 in our center were included.

MAIN OUTCOME MEASURES:
The outcome of interest was the need for an abdominal surgery within 1 year after the Lémann index evaluation at diagnosis.

RESULTS:
Of 212 eligible patients, 48 patients underwent abdominal surgery during follow-up. Lémann index was much higher in the surgery group (5.3 vs 2.6; p < 0.001). On tertiles of the Lémann index, the frequency of surgery grew (2.8%, 9.9%, and 55.7%; p < 0.001) as the Lémann index increased. The receiver operating characteristic curve was constructed taking into account the Lémann index for selecting patients with a high risk of surgery. Specificity, sensitivity, and area under receiver operating characteristic curve were 84.8%, 81.3%, and 0.89 of the Lémann Index at a cutoff level of 3.7. Patients with Lémann index ≥3.7 carried a higher risk of abdominal surgery (OR = 18.6; p < 0.001). Stricturing and penetrating disease were predictors for abdominal surgery, whereas antitumor necrosis factor treatment was associated with a significant reduction of surgical requirements.

LIMITATIONS:
This study was limited by its retrospective design. The ability of the Lémann index to predict the long-term risk of surgery was unknown.

CONCLUSIONS:
Lémann index at diagnosis is a reliable index to predict the risk of abdominal surgery in the first year after diagnosis of Crohn’s disease. Patients with a high Lémann index might need closer follow-up or aggressive medical therapy. See Video Abstract at http://links.lww.com/DCR/A518.
Comparison of Western and Asian Guidelines Concerning the Management of Colon Cancer
Authors: Pellino Gianluca , Warren Oliver , Mills Sarah , Rasheed Shahnawaz , Tekkis Paris P. , Kontovounisios Christos 
Published: January 2018

BACKGROUND:
Guidelines are important to standardize treatments and optimize outcomes. Several societies have published authoritative guidelines for patients with colon cancer, and a certain degree of variation can be predicted.

OBJECTIVE:
This study aims to compare Western and Asian guidelines for the management of colon cancer.

DATA SOURCES:
A literature review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for studies published between 2010 and 2017 by the online resources from the official Web sites of the societies/panels. Sources included guidelines by European Society of Medical Oncology, the Japanese Society for Cancer of the Colon and Rectum, and the National Comprehensive Cancer Network.

STUDY SELECTION:
Only full-text studies and the latest guidelines dealing with colon cancer were included. Studies and guidelines were separately assessed by 2 authors, who independently identified discrepancies and areas for further research. These were discussed and agreed with by all the authors.

MAIN OUTCOME MEASURES:
The recommendations of the guidelines of each society were compared, seeking discrepancies and potential areas for improvement.

RESULTS:
Endoscopic techniques for the management of early colon cancer are discussed in detail in the Asian guidelines. Asian guidelines advocate extended (D3) lymphadenectomy on a routine basis in T3/T4 and in selected T2 patients, whereas such an approach is still under investigation in Western countries. Only US guidelines describe neoadjuvant chemotherapy and radiotherapy. All the guidelines recommend adjuvant treatment in selected stage II patients, but agreement exists that this is performed without solid evidence, because better outcomes are hypothesized based on studies including stage III or stage II/III patients. The role of cytoreductive surgery with intra-abdominal chemotherapy is dubious, and European guidelines only recommend it in the setting of trials. Asian guidelines endorse an aggressive surgical approach to peritoneal disease. Only US guidelines include a patient advocate in the drafting panel.

LIMITATIONS:
Bias may have arisen from country-specific socioeconomic and cultural issues, and from the latest available updates.

CONCLUSIONS:
Surgical approaches to colon cancer differ significantly among Western and Asian guidelines, reflecting different concepts of treatment. The role of adjuvant treatment in node-negative disease and quality-of-life assessment need further research.
Adverse reactions to ophthalmic medicines
Authors: Badyal K.K. , Badyal I.S. 
Published: January 2018

Summary
Drugs used topically in the eye can cause systemic adverse effects that can range from mild to fatal. Ocular drugs can cause adverse effects by draining through the nasolacrimal duct and being absorbed into the blood stream, or by precipitating in the eye, or by causing an increase in intraocular pressure.
Acne Basics
Authors: Masterson Katrina Nice 
Published: January 2018

ABSTRACT
Acne is a chronic condition affecting the pilosebaceous unit. Presenting almost daily in the typical dermatology practice, the condition poses numerous treatment challenges due to the complex interaction of its clinical presentation and unique patient needs. The following discussion will provide basic pathophysiology and describe the clinical presentation of acne vulgaris and many of its variants. Several of the standard treatment options will be described. Uncommon variants, acute forms, and more complex treatment regimens will not be discussed here.
Clinical Use of Isotretinoin
Authors: Jellerichs Bradley 
Published: January 2018

ABSTRACT
Isotretinoin is an oral medication with clinical indications for several variants of acne. This medication is teratogenic and is associated with several adverse effects. It should be prescribed with appropriate caution in select patients. Recent evidence suggests a lack of correlation between isotretinoin use and diseases such as inflammatory bowel disease or depression. This article discusses the clinical use of oral isotretinoin by the dermatology nurse practitioner with a focus on management of adverse effects.
The ever-expanding saga of the proprotein convertases and their roles in body homeostasis: emphasis on novel proprotein convertase subtilisin kexin number 9 functions and regulation
Authors: Seidah Nabil G. , Chrétien Michel , Mbikay Majambu 
Published: January 2018

Purpose of review
The nine members of the proprotein convertase family play major physiological roles during development and in the adult, and their dysregulation leads to various diseases. The primary objective of this article is to review recent findings on the clinical importance of some of these convertases concentrating mostly on PCSK9, the ninth member of the convertase family. This includes the transcriptional and translational regulation of PCSK9, its ability to enhance the degradation of LDL receptor (LDLR), and the implication of PCSK9 in inflammation and sepsis.

Recent findings
PCSK9 levels are upregulated by E2F1 and reduced by specific miRNAs and by Annexin A2 that bind the 3’ end of its mRNA. The implication of the LDLR in the clearance of pathogenic bacterial debris in mice and human puts in perspective a new role for PCSK9 in the regulation of sepsis. The specific implication of the LDLR in the clearance of Lp(a) is now confirmed by multiple studies of PCSK9 inhibition in human cohorts.

Summary
Emerging data suggest that PCSK9 can be regulated at the transcriptional and translational levels by specific factors and miRNAs. The identification of a novel pocket in the catalytic domain of PCSK9 represents a harbinger for a new class of small inhibitor drugs. The implication of the LDLR in reducing the effects of bacterially induced sepsis has been supported by both human and mouse data. Outcome studies confirmed the clinical importance of reducing PCSK9 levels. The present review puts in perspective new developments in the PCSK9 biology and its regulation of the LDLR.

Video abstract

http://links.lww.com/COL/A17
New antibiotics for ventilator-associated pneumonia
Authors: Bassetti Matteo , Vena Antionio , Castaldo Nadia , Righi Elda , Peghin Maddalena 
Published: January 2018

Purpose of review
Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) bacteria represents a global emerging problem. Delayed prescription of an adequate treatment for VAP has been associated with higher morbidity and mortality. New molecules have been developed to face the need of compounds that are active against resistant Gram-positive and Gram-negative pathogens. The aim of this review is to summarize the current scenario of new therapeutic options for the treatment of VAP.

Recent findings
A number of new antibiotics with activity against MDR have been recently approved for the treatment of VAP, and other agents are under investigation. In this review, the authors summarize the current therapeutic options for the treatment of VAP that showed promising implications for clinical practice, including new compounds belonging to old antibiotic classes (e.g., ceftolozane/tazobactam, ceftazidime/avibactam meropenem/vaborbactam, imipenem/relebactam, tedizolid, cefiderocol, eravacycline, and plazomicin) and novel chemical classes, such as murepavadin. Nebulized antibiotics that are currently in development for the treatment of pneumonia in mechanically ventilated patients are also presented.

Summary
Newly approved and investigational drugs for the treatment of VAP are expected to offer many advantages for the management of patients with respiratory infections caused by MDR. Promising characteristics of new compounds include high activity against both methicillin-resistant Staphylococcus aureus and MDR Gram-negative bacteria and a favorable safety profile.
Frequency and Severity of Acute Allergic-Like Reactions to Intravenously Administered Gadolinium-Based Contrast Media in Children
Authors: Forbes-Amrhein Monica M. , Dillman Jonathan R. , Trout Andrew T. , Koch Bernadette L. , Dickerson Julie M. , Giordano Richard M. , Towbin Alexander J. 
Published: January 2018

Objectives
The purpose of this study is to determine the frequency and severity of acute allergic-like reactions to gadolinium-based contrast media (GBCM) in children before, during, and after the transition from gadopentetate dimeglumine to gadoterate meglumine as our primary clinical GBCM.

Materials and Methods
Institutional review board approval was obtained for this Health Insurance Portability and Accountability Act–compliant retrospective investigation. Allergic-like reactions to GBCM in pediatric patients were retrospectively assessed from January 2009 to January 2017, which included a departmental change of GBCM from gadopentetate dimeglumine to gadoterate meglumine. Allergic-like reactions were identified from departmental and hospital databases. The number of doses of GBCM was obtained from billing data. Allergic-like reaction frequencies for each GBCM were calculated and compared using the chi-squared test.

Results
A total of 32,365 administrations of GBCM occurred during the study period (327 for gadofosveset trisodium; 672 for gadoxetate disodium; 12,012 for gadoterate meglumine; and 19,354 for gadopentetate dimeglumine). Allergic-like reactions occurred after 21 (0.06%) administrations. Reaction frequencies were not significantly different among the GBCM (0.3% gadofosveset trisodium; 0% gadoxetate disodium, 0.06% gadoterate meglumine, 0.08% gadopentetate dimeglumine; P > 0.05). Ten (47.6%) reactions were mild, 10 (47.6%) were moderate, and 1 (4.8%) was severe. The overall reaction frequency peaked during the 6-month transition period from gadopentetate dimeglumine to gadoterate meglumine (0.20%), compared with 0.07% pretransition (P = 0.048) and 0.04% posttransition (P = 0.0095).

Conclusion
Allergic-like reactions to GBCM in children are rare. Gadoterate meglumine has a reaction frequency that does not significantly differ from other GBCMs. During the transition from gadopentetate dimeglumine to gadoterate meglumine, an increase in the frequency of reported allergic-like reactions was observed, likely reflective of the Weber effect.
Serum Admission 25-Hydroxyvitamin D Levels and Outcomes in Initially Non-Septic Critically Ill Patients
Authors: Vassiliou Alice G. , Jahaj Edison , Mastora Zafeiria , Stagaki Eleni , Orfanos Stylianos E. , Kotanidou Anastasia 
Published: January 2018

ABSTRACT

Introduction:
To examine whether very low levels of 25-hydroxyvitamin D {25(OH)D} upon admission to the intensive care unit (ICU) are associated with worse outcomes.

Methods:
Retrospective observational cohort study of critically ill patients treated in a multidisciplinary ICU. Two hundred twenty seven initially non-septic, critically ill patients, in whom 25-hydroxyvitamin D was measured at ICU admission. An additional group of 192 healthy subjects was also used. Patients were categorized according to their vitamin D levels at admission; the two patient groups were those with severely low 25-hydroxyvitamin D levels (<7 ng/mL, N = 101) and those with vitamin D levels ≥7 ng/mL, N = 126.

Results:
ICU admission 25-hydroxyvitamin D levels of critically ill patients were much lower than those of healthy subjects (P < 0.0001). The median time to sepsis for the two patient groups did not differ, nor did the length of ICU stay (days). Both groups exhibited similar hospital mortality rates. However, among the fraction of patients who eventually became septic (N = 145), the odds ratio (OR) for developing respiratory infections in patients with admission vitamin levels < 7 ng/mL compared with patients with admission vitamin D levels ≥7 ng/mL was 5.25 {95% confidence interval (CI) 1.5–18.32, P = 0.009}.

Conclusions:
Initially non-septic critically ill patients appear to have very low ICU admission 25-hydroxyvitamin D levels. Among critically ill patients, severely low vitamin D levels (<7 ng/mL) at ICU admission do not predict sepsis development, increased risk of in-hospital mortality, or longer stay in the ICU. However, these severely low admission vitamin D levels in patients who will eventually develop sepsis are associated with development of respiratory tract infections.
Identifying long indels in exome sequencing data of patients with intellectual disability
Authors: Pajusalu Sander , Pfundt Rolph , Vissers Lisenka E.L.M. , Kwint Michael P. , Reimand Tiia , Õunap Katrin , Veltman Joris A. , Hehir-Kwa Jayne Y. 
Published: January 2018

AbstractExome sequencing is a powerful tool for detecting both single and multiple nucleotide variation genome wide. However long indels, in the size range 20 – 200bp, remain difficult to accurately detect. By assessing a set of common exonic long indels, we estimate the sensitivity of long indel detection in exome sequencing data to be 92%. To clarify the role of pathogenic long indels in patients with intellectual disability (ID), we analysed exome sequencing data from 820 patients using two variant callers, Pindel and Platypus. We identified three indels explaining the patients’ clinical phenotype by disrupting the UBE3A, PGAP3 and MECP2 genes. Comparison of different tools demonstrated the importance of both correct genotyping and annotation variants. In conclusion, specialized long indel detection can improve diagnostic yield in ID patients.
The mammalian decidual cell evolved from a cellular stress response
Authors: Erkenbrack Eric M. , Maziarz Jamie D. , Griffith Oliver W. , Liang Cong , Chavan Arun R. , Wagner Günter P. 
Published: January 2018

AbstractAmong animal species, cell types vary greatly in terms of number and kind. The broad range of number of cell types among species suggests that cell type origination is a significant source of evolutionary novelty. The molecular mechanisms giving rise to novel cell types, however, are poorly understood. Here we show that a novel cell type of eutherian mammals, the decidual stromal cell (DSC), evolved by rewiring an ancestral cellular stress response. We isolated the precursor cell type of DSCs, endometrial stromal fibroblasts (ESFs), from the opossum Monodelphis domestica. We show that, in opossum ESF, the majority of decidual core regulatory genes respond to decidualizing signals, but do not regulate decidual effector genes. Rather, in opossum ESF, decidual transcription factors function in apoptotic and oxidative stress response. We propose that the rewiring of cellular stress responses could be a general mechanism for the evolution of novel cell types.
Hierarchical optimization for the efficient parametrization of ODE models
Authors: Loos Carolin , Krause Sabrina , Hasenauer Jan 
Published: January 2018

AbstractMathematical models are nowadays important tools for analyzing dynamics of cellular processes. The unknown model parameters are usually estimated from experimental data. These data often only provide information about the relative changes between conditions, hence, the observables contain scaling parameters. The unknown scaling parameters and corresponding noise parameters have to be inferred along with the dynamic parameters. The nuisance parameters often increase the dimensionality of the estimation problem substantially and cause convergence problems. In this manuscript, we propose a hierarchical optimization approach for estimating the parameters for ordinary differential equation (ODE) models from relative data. Our approach restructures the optimization problem into an inner and outer subproblem. These subproblems possess lower dimensions than the original optimization problem, and the inner problem can be solved analytically. We evaluated accuracy, robustness, and computational efficiency of the hierarchical approach by studying three signaling pathways. The proposed approach achieved better convergence than the standard approach and required a lower computation time. As the hierarchical optimization approach is widely applicable, it provides a powerful alternative to established approaches.
miRNAs play important roles in aroma weakening during the shelf life of ‘Nanguo’ pear after cold storage
Authors: Shi Fei , Zhou Xin , Yao Miao-miao , Tan Zhuo , Zhou Qian , Zhang Lei , Ji Shu-juan 
Published: January 2018

AbstractCold storage is commonly employed to delay senescence in ‘Nanguo’ pears after harvest. However, this technique also causes fruit aroma weakening. MicroRNAs play important roles in plant development and in eliciting responses to abiotic environmental stressors. In this study, the miRNA transcript profile of the fruit at the first day (C0, LT0) move in and out of cold storage and the optimum tasting period (COTP, LTOTP) during shelf life at room temperature were analyzed, respectively. More than 300 known miRNAs were identified in ‘Nanguo’ pears; 176 and 135 miRNAs were significantly differentially expressed on the C0vs. LT0 and on the COTP vs. LTOTP, respectively. After prediction the target genes of these miRNAs,LOX2S,LOX1_5,HPL, andADH1were found differentially expressed, which were the key genes during aroma formation. The expression pattern of these target genes and the related miRNAs were identified by RT-PCR. Mdm-miR172a-h, mdm-miR159a/b/c, mdm-miR160a-e, mdm-miR395a-i, mdm/ppe-miR399a, mdm/ppe-miR535a/b, and mdm-miR7120a/b negatively regulated target gene expression. These results indicate that miRNAs play key roles in aroma weakening in refrigerated ‘Nanguo’ pear and provide valuable information for studying the molecular mechanisms of miRNAs in the aroma weakening of fruits due to cold storage.
Data-driven characterization of molecular phenotypes across heterogenous sample collections
Authors: Mehtonen J. , Pölönen P. , Häyrynen S. , Lin J. , Liuksiala T. , Granberg K. , Lohi O. , Hautamäki V. , Nykter M. , Heinäniemi M. 
Published: January 2018

AbstractThe existing large gene expression data repositories hold enormous potential to elucidate disease mechanisms, characterize changes in cellular pathways, and to stratify patients based on their molecular profile. To achieve this goal, integrative resources and tools are needed that allow comparison of results across datasets and data types. We propose an intuitive approach for data-driven stratifications of molecular profiles and benchmark our methodology using the dimensional reduction algorithm t-SNE with multi-center and multi-platform data representing hematological malignancies. Our approach enables assessing the contribution of biological versus technical variation to sample clustering, direct incorporation of additional datasets to the same low dimensional representation of molecular disease subtypes, comparison of sample groups between separate t-SNE representations, or maps, and characterization of the obtained clusters based on pathway databases and additional multi-omics data. In the example application, our approach revealed differential activity of SAM-dependent DNA methylation pathway in the acute myeloid leukemia patient cluster characterized with CEBPA mutations that accordingly was validated to have globally elevated DNA methylation levels.