bluuebunny/crossref_metadata_2025 huggingface dataset:
Conserved salt-bridge competition triggered by phosphorylation regulates the protein interactome
Authors: Skinner John J. , Wang Sheng , Lee Jiyoung , Ong Colin , Sommese Ruth , Sivaramakrishnan Sivaraj , Koelmel Wolfgang , Hirschbeck Maria , Schindelin Hermann , Kisker Caroline , Lorenz Kristina , Sosnick Tobin R. , Rosner Marsha Rich
Published: December 2017

Significance

Phosphorylation is a ubiquitous modification that has been implicated in signaling and other functions, but the atomic-level mechanisms are not completely understood. We identify a salt-bridge competition or “theft” mechanism wherein a phosphoserine, but not a phosphomimetic, breaks a pre-existing salt bridge, initiating a partial unfolding event and promoting new protein interactions. Structural elements underlying the theft occurred early in evolution and are found in 10% of homo-oligomers and 30% of hetero-oligomers. These findings identify a facile and evolutionarily accessible mechanism for reorganizing salt bridges and other electrostatic networks with only a single mutation to trigger a functional switch.
What Chern–Simons theory assigns to a point
Authors: Henriques André G.
Published: December 2017

Significance

There are two main classes of 3D topological field theories: Turaev–Viro theories, associated to fusion categories, and Reshetikhin–Turaev theories, associated to modular tensor categories. Since the groundbreaking work by Lurie on the cobordism hypothesis, it has been a major open question to know which topological field theories (TFTs) extend down to points. Turaev–Viro theories can be extended down to points. But for most Reshetikhin–Turaev theories, including Chern–Simons theories, this was believed to be impossible (unless one puts them on the boundary of a 4D TFT). The present paper achieves two things: It shows that Reshetikhin–Turaev theories extend down to points, and it puts Turaev–Viro theories and Reshetikhin–Turaev theories on an equal footing by providing a unified language, bicommutant categories, that applies to both.
Recurring infection with ecologically distinct HPV types can explain high prevalence and diversity
Authors: Ranjeva Sylvia L. , Baskerville Edward B. , Dukic Vanja , Villa Luisa L. , Lazcano-Ponce Eduardo , Giuliano Anna R. , Dwyer Greg , Cobey Sarah
Published: December 2017

Significance

Human papillomavirus (HPV) is the most common sexually transmitted infection. Understanding the factors underlying the prevalence and diversity of over 200 HPV types is necessary to predict the effects of multivalent vaccines. We investigate HPV transmission dynamics by fitting mechanistic models to data from unvaccinated men. We find that infection risk in a susceptible population is, on average, low and concentrated in high-risk individuals and that, rather than inducing protective immunity, HPV infection strongly increases the risk of future infection by the same type. Thus, high HPV prevalence results from frequent reinfection or persistent infections within individuals. Vaccinating boys before their first HPV exposure may be especially effective in reducing prevalence, and vaccinating previously infected men may also be effective.
Aminoglycoside interactions and impacts on the eukaryotic ribosome
Authors: Prokhorova Irina , Altman Roger B. , Djumagulov Muminjon , Shrestha Jaya P. , Urzhumtsev Alexandre , Ferguson Angelica , Chang Cheng-Wei Tom , Yusupov Marat , Blanchard Scott C. , Yusupova Gulnara
Published: December 2017

Significance

Aminoglycosides are well known as antibiotics that target the bacterial ribosome. However, they also impact the eukaryotic translation mechanism to promote read-through of premature termination codons (PTCs) in mRNA. Aminoglycosides are therefore considered as potential therapies for PTC-associated human diseases. Here, we performed a comprehensive study of the mechanism of action of aminoglycosides in eukaryotes by applying a combination of structural and functional approaches. Our findings reveal complex interactions of aminoglycosides with eukaryotic 80S ribosome caused by their multiple binding sites, which lead to inhibition of intersubunit movement within the human ribosome that impact nearly every aspect of protein synthesis.
Ant colony optimization and event-based dynamic task scheduling and staffing for software projects
Authors: Ellappan Vijayan , Ashwini J
Published: December 2017

In programming change organizations from medium to inconceivable scale broadens, the issue of wander orchestrating is amazingly unusual and testing undertaking despite considering it a manual system. Programming wander-organizing requirements to deal with the issue of undertaking arranging and in addition the issue of human resource portion (also called staffing) in light of the way that most of the advantages in programming ventures are individuals. We propose a machine learning approach with finds respond in due order regarding booking by taking in the present arranging courses of action and an event based scheduler revives the endeavour arranging system moulded by the learning computation in perspective of the conformity in event like the begin with the Ander, the instant at what time possessions be free starting to ended errands, and the time when delegates stick together otherwise depart the wander inside the item change plan. The route toward invigorating the timetable structure by the even based scheduler makes the arranging method dynamic. It uses structure components to exhibit the interrelated surges of endeavours, slip-ups and singular all through different progression organizes and is adjusted to mechanical data. It increases past programming wander movement ask about by taking a gander at a survey based process with a one of a kind model, organizing it with the data based system for peril assessment and cost estimation, and using a choice showing stage.
FROGS: Find, Rapidly, OTUs with Galaxy Solution
Authors: Escudié Frédéric , Auer Lucas , Bernard Maria , Mariadassou Mahendra , Cauquil Laurent , Vidal Katia , Maman Sarah , Hernandez-Raquet Guillermina , Combes Sylvie , Pascal Géraldine
Published: December 2017

Motivation

Metagenomics leads to major advances in microbial ecology and biologists need user friendly tools to analyze their data on their own.

Results

This Galaxy-supported pipeline, called FROGS, is designed to analyze large sets of amplicon sequences and produce abundance tables of Operational Taxonomic Units (OTUs) and their taxonomic affiliation. The clustering uses Swarm. The chimera removal uses VSEARCH, combined with original cross-sample validation. The taxonomic affiliation returns an innovative multi-affiliation output to highlight databases conflicts and uncertainties. Statistical results and numerous graphical illustrations are produced along the way to monitor the pipeline. FROGS was tested for the detection and quantification of OTUs on real and in silico datasets and proved to be rapid, robust and highly sensitive. It compares favorably with the widespread mothur, UPARSE and QIIME.

Availability and implementation

Source code and instructions for installation: https://github.com/geraldinepascal/FROGS.git. A companion website: http://frogs.toulouse.inra.fr.

Supplementary information

Supplementary data are available at Bioinformatics online.
SPRING: a kinetic interface for visualizing high dimensional single-cell expression data
Authors: Weinreb Caleb , Wolock Samuel , Klein Allon M
Published: December 2017

Motivation

Single-cell gene expression profiling technologies can map the cell states in a tissue or organism. As these technologies become more common, there is a need for computational tools to explore the data they produce. In particular, visualizing continuous gene expression topologies can be improved, since current tools tend to fragment gene expression continua or capture only limited features of complex population topologies.

Results

Force-directed layouts of k-nearest-neighbor graphs can visualize continuous gene expression topologies in a manner that preserves high-dimensional relationships and captures complex population topologies. We describe SPRING, a pipeline for data filtering, normalization and visualization using force-directed layouts and show that it reveals more detailed biological relationships than existing approaches when applied to branching gene expression trajectories from hematopoietic progenitor cells and cells of the upper airway epithelium. Visualizations from SPRING are also more reproducible than those of stochastic visualization methods such as tSNE, a state-of-the-art tool. We provide SPRING as an interactive web-tool with an easy to use GUI.

Availability and implementation

https://kleintools.hms.harvard.edu/tools/spring.html, https://github.com/AllonKleinLab/SPRING/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Gene Graphics: a genomic neighborhood data visualization web application
Authors: Harrison Katherine J , Crécy-Lagard Valérie de , Zallot Rémi
Published: December 2017

The examination of gene neighborhood is an integral part of comparative genomics but no tools to produce publication quality graphics of gene clusters are available. Gene Graphics is a straightforward web application for creating such visuals. Supported inputs include National Center for Biotechnology Information gene and protein identifiers with automatic fetching of neighboring information, GenBank files and data extracted from the SEED database. Gene representations can be customized for many parameters including gene and genome names, colors and sizes. Gene attributes can be copied and pasted for rapid and user-friendly customization of homologous genes between species. In addition to Portable Network Graphics and Scalable Vector Graphics, produced representations can be exported as Tagged Image File Format or Encapsulated PostScript, formats that are standard for publication. Hands-on tutorials with real life examples inspired from publications are available for training.

Availability and implementation

Gene Graphics is freely available at https://katlabs.cc/genegraphics/ and source code is hosted at https://github.com/katlabs/genegraphics.

Supplementary information

Supplementary data are available at Bioinformatics online.
Matrix factorization-based data fusion for the prediction of lncRNA–disease associations
Authors: Fu Guangyuan , Wang Jun , Domeniconi Carlotta , Yu Guoxian
Published: December 2017

Motivation

Long non-coding RNAs (lncRNAs) play crucial roles in complex disease diagnosis, prognosis, prevention and treatment, but only a small portion of lncRNA–disease associations have been experimentally verified. Various computational models have been proposed to identify lncRNA–disease associations by integrating heterogeneous data sources. However, existing models generally ignore the intrinsic structure of data sources or treat them as equally relevant, while they may not be.

Results

To accurately identify lncRNA–disease associations, we propose a Matrix Factorization based LncRNA–Disease Association prediction model (MFLDA in short). MFLDA decomposes data matrices of heterogeneous data sources into low-rank matrices via matrix tri-factorization to explore and exploit their intrinsic and shared structure. MFLDA can select and integrate the data sources by assigning different weights to them. An iterative solution is further introduced to simultaneously optimize the weights and low-rank matrices. Next, MFLDA uses the optimized low-rank matrices to reconstruct the lncRNA–disease association matrix and thus to identify potential associations. In 5-fold cross validation experiments to identify verified lncRNA–disease associations, MFLDA achieves an area under the receiver operating characteristic curve (AUC) of 0.7408, at least 3% higher than those given by state-of-the-art data fusion based computational models. An empirical study on identifying masked lncRNA–disease associations again shows that MFLDA can identify potential associations more accurately than competing models. A case study on identifying lncRNAs associated with breast, lung and stomach cancers show that 38 out of 45 (84%) associations predicted by MFLDA are supported by recent biomedical literature and further proves the capability of MFLDA in identifying novel lncRNA–disease associations. MFLDA is a general data fusion framework, and as such it can be adopted to predict associations between other biological entities.

Availability and implementation

The source code for MFLDA is available at: http://mlda.swu.edu.cn/codes.php? name = MFLDA.

Supplementary information

Supplementary data are available at Bioinformatics online.
Does Podcast Use Enhance Critical Thinking in Nursing Education?
Authors: Blum Cynthia A.
Published: December 2017

The purpose of this pilot interventional study was to examine relationships between adjunctive podcast viewing and nursing students' critical thinking (CT) abilities. Participants were last semester/preceptorship nursing students. The intervention group was given unrestricted access to a CT podcast. There was no statistical significance between Health Sciences Reasoning Test pretest and posttest scores, the number of times the podcast was viewed, and specific demographic factors. The results suggest that CT podcast viewing did not improve CT abilities. However, Likert scale results indicated students liked this method of learning. Demographic factors and sample size were limited, and further research is recommended.
Primary care management of ulcerative colitis
Authors: Davis Stephanie C. , Robinson Brittani L. , Vess Joy , Lebel Joseph S.
Published: December 2017

Ulcerative colitis (UC) is an inflammatory bowel disease marked by mucosal inflammation. UC has an impact on quality of life and places a financial burden on the healthcare system. This article focuses on the impact, presentation, diagnosis and classification, systemic manifestations, complications, management, and treatment associated with UC.
Descriptive Analysis of State and Federal Spine Surgery Malpractice Litigation in the United States
Authors: Agarwal Nitin , Gupta Raghav , Agarwal Prateek , Matthew Pravin , Wolferz Richard , Shah Aakash , Adeeb Nimer , Prabhu Arpan V. , Kanter Adam S. , Okonkwo David O. , Hamilton David Kojo
Published: December 2017

Study Design.

A retrospective review.

Objective.

This study aimed to determine the factors associated with malpractice litigation in cases involving spine surgery in the United States.

Summary of Background Data.

Medical malpractice is of substantial interest to the medical community due to concerns of increased health care costs and medical decision-making for the sole purpose of reducing legal liability.

Methods.

The Westlaw online legal database (Thomson Reuters, New York, NY) was searched for verdict and settlement reports pertaining to spine surgery from 2010 to 2015. Data were collected regarding type of procedure, patient age and gender, defendant specialty, outcome, award, alleged cause of malpractice, and factors involved in the plaintiff's decision to file. Initial search queried 187 cases, after which exclusion criteria were applied to eliminate duplicates and cases unrelated to spine surgery, yielding a total of 98 cases for analysis.

Results.

The verdict was in favor of the defendant in 62 cases (63.3%). Neurosurgeons and orthopedic surgeons were the most common defendants in 29 (17.3%) and 40 (23.8%) of the cases, respectively. A perceived lack of informed consent was noted as a factor in 24 (24.4%) of the cases. A failure to diagnose or a failure to treat was noted in 31 (31.6%) and 32 (32.7%) cases, respectively. Median payments for plaintiff verdicts were nearly double those of settlements ($2,525,000 vs. $1,300,000). A greater incidence of plaintiff verdicts was noted in cases in which a failure to treat (P < 0.05) was cited, a patient death occurred (P < 0.05), or an emergent surgery had been performed (P < 0.01).

Conclusion.

Overall, physicians were not found liable in the majority of spine surgery malpractice cases queried.

Level of Evidence: 4
Comparing Health-Related Quality of Life Outcomes in Patients Undergoing Either Primary or Revision Anterior Cervical Discectomy and Fusion
Authors: Schroeder Gregory D. , Boody Barrett S. , Kepler Christopher K. , Kurd Mark F. , Silva Stephen , Nicholson Kristen , Wilson Jefferson R. , Woods Barret I. , Radcliff Kris E. , Anderson David Greg , Hilibrand Alan S. , Vaccaro Alexander R. , Rihn Jeffery A.
Published: December 2017

Study Design.

A retrospective review of prospectively collected data.

Objective.

Compare health-related quality of life (HRQOL) outcome metrics in patients undergoing primary and revision anterior cervical discectomy and fusion (ACDF).

Summary of Background Data.

ACDF is associated with significant improvements in HRQOL outcome metrics. However, 2.9% of patients per year will develop symptomatic adjacent segment disease and there is a paucity of literature on HRQOL outcomes after revision ACDF.

Methods.

Patients were identified who underwent either a primary or revision ACDF, and who had both preoperative and a minimum of 1-year postoperative HRQOL outcome data. Pre- and postoperative Short Form 12 Physical Component Score (SF12 PCS), Short Form 12 Mental Component Score (SF12 MCS) Visual Analog Scale for neck pain (VAS-Neck), VAS-Arm, and Neck Disability Index (NDI) scores were compared.

Results.

A total of 360 patients (299 primary, 61 revision) were identified. Significant improvement in SF12 PCS, NDI, VAS-Neck, and VAS-Arm was seen in both groups; however, only a significant improvement in SF12 MCS was seen in the primary group. When comparing the results of a primary versus a revision surgery, the SF12 PCS score was the only outcome with a significantly different net improvement in the primary group (7.23 ± 9.72) compared to the revision group (2.9 ± 11.07; P = 0.006) despite similar baseline SF12 PCS scores. The improvement in each of the other reported HRQOL outcomes did not significantly vary between surgical groups.

Conclusion.

A revision ACDF for cervical radiculopathy or myelopathy leads to a significant improvement in the HRQOL outcome, and with the exception of the SF12 PCS, these results are similar to those of patients undergoing a primary ACDF.

Level of Evidence: 2
Postoperative Deep Vein Thrombosis, Pulmonary Embolism, and Myocardial Infarction
Authors: Shiu Brian , Le Elizabeth , Jazini Ehsan , Weir Tristan B. , Costales Timothy , Caffes Nicholas , Paryavi Ebrahim , O’Hara Nathan , Gelb Daniel E. , Koh Eugene Y. , Ludwig Steven C.
Published: December 2017

Study Design.

A retrospective review (2001–2014) was conducted using prospectively collected data at a level I trauma center.

Objective.

We sought to determine the incidence and characteristics of complications occurring secondary to therapeutic anticoagulation in adult spine trauma patients.

Summary of Background Data.

Numerous studies have assessed prophylactic anticoagulation after spine surgery, but none has investigated the risks of therapeutic doses of anticoagulation for treatment of postoperative thromboembolic events.

Methods.

Patients were included if they sustained a postoperative thromboembolic event (deep venous thrombosis, pulmonary embolism, or myocardial infarction). Patients were excluded if anticoagulation was subtherapeutic. Of 1712 patients, 62 who received therapeutic anticoagulation and 174 propensity-matched control patients who did not receive therapeutic anticoagulation were included in the study.

Results.

Initial anticoagulation was obtained by heparin infusion (51%), low-molecular-weight heparin (LMWH, 46%), and warfarin (3%). Complications requiring unplanned reoperation occurred in 18% of anticoagulated patients and 10% of nonanticoagulated patients (P = 0.17). The reoperation rate after heparin infusion was 31% and after LMWH was 6.5% (P = 0.02). Epidural hematoma occurred in 3% and 1% of anticoagulated and nonanticoagulated patients, respectively. Multivariate logistic regression analysis of the two groups showed a trend toward increased risk of reoperation in the anticoagulation group. Analysis of the heparin infusion subgroup separate from the LMWH subgroup compared with the control group showed an increased risk of reoperation for any complication (odds ratio, 3.57; P = 0.01) and for bleeding complications (odds ratio, 43.1; P = 0.01).

Conclusion.

This is the first study to quantify complications secondary to postoperative therapeutic anticoagulation in spine patients. Postoperative spine trauma patients who underwent therapeutic anticoagulation experienced an unplanned reoperation rate of 18%, including a 3% incidence of spinal epidural hematoma. Therapeutic anticoagulation using heparin infusion seems to drive the overall rate of reoperation (31%) compared with LMWH.

Level of Evidence: 3
The New York Sepsis Severity Score: Development of a Risk-Adjusted Severity Model for Sepsis
Authors: Phillips Gary S. , Osborn Tiffany M. , Terry Kathleen M. , Gesten Foster , Levy Mitchell M. , Lemeshow Stanley
Published: December 2017

Objectives:

In accordance with Rory’s Regulations, hospitals across New York State developed and implemented protocols for sepsis recognition and treatment to reduce variations in evidence informed care and preventable mortality. The New York Department of Health sought to develop a risk assessment model for accurate and standardized hospital mortality comparisons of adult septic patients across institutions using case-mix adjustment.

Design:

Retrospective evaluation of prospectively collected data.

Patients:

Data from 43,204 severe sepsis and septic shock patients from 179 hospitals across New York State were evaluated.

Settings:

Prospective data were submitted to a database from January 1, 2015, to December 31, 2015.

Interventions:

None.

Measurement and Main Results:

Maximum likelihood logistic regression was used to estimate model coefficients used in the New York State risk model. The mortality probability was estimated using a logistic regression model. Variables to be included in the model were determined as part of the model-building process. Interactions between variables were included if they made clinical sense and if their p values were less than 0.05. Model development used a random sample of 90% of available patients and was validated using the remaining 10%. Hosmer-Lemeshow goodness of fit p values were considerably greater than 0.05, suggesting good calibration. Areas under the receiver operator curve in the developmental and validation subsets were 0.770 (95% CI, 0.765–0.775) and 0.773 (95% CI, 0.758–0.787), respectively, indicating good discrimination. Development and validation datasets had similar distributions of estimated mortality probabilities. Mortality increased with rising age, comorbidities, and lactate.

Conclusions:

The New York Sepsis Severity Score accurately estimated the probability of hospital mortality in severe sepsis and septic shock patients. It performed well with respect to calibration and discrimination. This sepsis-specific model provides an accurate, comprehensive method for standardized mortality comparison of adult patients with severe sepsis and septic shock.
Numeracy and Interpretation of Prognostic Estimates in Intracerebral Hemorrhage Among Surrogate Decision Makers in the Neurologic ICU
Authors: Leiter Nikita , Motta Melissa , Reed Robert M. , Adeyeye Temitope , Wiegand Debra L. , Shah Nirav G. , Verceles Avelino C. , Netzer Giora
Published: December 2017

Objective:

Clinicians caring for patients with intracerebral hemorrhage must often discuss prognosis and goals of care with their patients’ surrogate decision makers, and may make numeric estimates of likelihood of survival and functional independence, informed by validated prediction models. Surrogates’ prognostic estimates are often discordant with physicians’, suggesting that physicians’ numeric statements may not be accurately interpreted. We sought to assess the relationship between numeracy and interpretation of prognostic estimates in intracerebral hemorrhage among surrogate decision makers. We also assessed surrogates’ application of prognostic estimates to decisions regarding goals of care.

Design:

Single-center, survey-based, cross-sectional study.

Setting:

Twenty-two–bed neurologic ICU at an urban, academic hospital.

Subjects:

Surrogate decision makers for patients admitted to the neurologic ICU.

Interventions:

Participants completed a survey containing five clinical vignettes describing patients with nontraumatic intracerebral hemorrhage. For each patient, numerical estimates of survival and functional independence were explicitly provided, based on the validated outcome risk stratification scale (intracerebral hemorrhage score) and the Prediction of Functional Outcome in Patients with Primary Intracerebral Hemorrhage score.

Measurements and Main Results:

Participants were asked to make their own prognostic estimates, as well as to describe their preferred goals of care for each hypothetical patient. Respondent demographics were collected, and numeracy was assessed using a modified Lipkus 11-item scale. Poor numeracy was common (42 of 96 total subjects) in this relatively highly educated population. Most prognostic estimates (55%) made by surrogates were discordant with the provided estimates. High numeracy correlated with better concordance (odds ratio, 23.9 [5.57–97.64]; p < 0.001), independent of several factors, including level of education and religion. Numeracy also affected goals-of-care decisions made by surrogates.

Conclusions:

Poor numeracy is common among surrogate decision makers in an intensive care setting and poses a barrier to communication between surrogates and clinicians regarding prognosis and goals of care.
Hemorrhage of liver and bone metastases as a result of rapid response to dual BRAF/MEK inhibition in metastatic melanoma: a case report
Authors: Loyson Tine , Werbrouck Emilie , Punie Kevin , Bonne Lawrence , Vandecaveye Vincent , Bechter Oliver
Published: December 2017

Combination therapy using a BRAF and MEK inhibitor significantly improves both progression-free and overall survival in patients with BRAF V600-mutated stage IV melanoma. Dual MAPK inhibition achieves an objective response in the majority of patients. We present a case of a woman with BRAF V600E-mutated malignant melanoma and rapidly progressing liver, bone, and lymph node metastases. The patient commenced dabrafenib and trametinib with clinical and biochemical signs of response after 2 days. On day 3 she developed grade 3 liver hemorrhage, which was successfully embolized. Her anemia responded appropriately to transfusions and stabilized after interventional resolution of the hemorrhagic event. Subsequently she developed a pathological fracture of the right proximal humerus. MRI showed cystic bone metastases with stigmata of bleeding. To our knowledge, this is the first case report of a patient with hemorrhage of both liver and bone metastases of a melanoma. As the patient responded rapidly to dabrafenib and trametinib we hypothesize that the hemorrhage may be due to rapid tumor necrosis and bleeding of affected tumor supplying blood vessels. Our case demonstrates the importance of considering tumoral bleeding as a side effect of BRAF and MEK inhibition in responding melanoma patients. Mechanical intervention can be effective in resolving this treatment-related adverse event.
Cardiosphere-Derived Cells and Ischemic Heart Failure
Authors: Ashur Carmel , Frishman William H.
Published: December 2017

After a myocardial infarction, heart tissue becomes irreversibly damaged, leading to scar formation and inevitably ischemic heart failure. Of the many available interventions after a myocardial infarction, such as percutaneous intervention or pharmacological optimization, none can reverse the ischemic insult on the heart and restore cardiac function. Thus, the only available cure for patients with scarred myocardium is allogeneic heart transplantation, which comes with extensive costs, risks, and complications. However, multiple studies have shown that the heart is, in fact, not an end-stage organ and that there are endogenous mechanisms in place that have the potential to spark regeneration. Stem cell therapy has emerged as a potential tool to tap into and activate this endogenous framework. Particularly promising are stem cells derived from cardiac tissue itself, referred to as cardiosphere-derived cells (CDCs). CDCs can be extracted and isolated from the patient’s myocardium and then administered by intramyocardial injection or intracoronary infusion. After early success in the animal model, multiple clinical trials have demonstrated the safety and efficacy of autologous CDC therapy in humans. Clinical trials with allogeneic CDCs showed early promising results and pose a potential “off-the-shelf” therapy for patients in the acute setting after a myocardial infarction. The mechanism responsible for CDC-induced cardiac regeneration seems to be a combination of triggering native cardiomyocyte proliferation and recruitment of endogenous progenitor cells, which most prominently occurs via paracrine effects. A further understanding of the mediators involved in paracrine signaling can help with the development of a stem cell–free therapy, with all the benefits and none of the associated complications.
Assessment of Ileostomy Output Using Telemedicine: A Feasibility Trial
Authors: Bednarski Brian K. , Slack Rebecca S. , Katz Matthew , You Y. Nancy , Papadopolous John , Rodriguez-Bigas Miguel A. , Skibber John M. , Matin Surena F. , Chang George J.
Published: December 2017

BACKGROUND:

Ileostomies are a routine part of the care of patients with rectal cancer, but are associated with significant risk for dehydration, readmission, and acute kidney injury. Telemedicine has proven beneficial in decreasing readmission in chronic medical illnesses, but its utility in patients with an ileostomy is not well studied.

OBJECTIVE:

The purpose of this study was to evaluate the feasibility of televideoconferencing in the assessment of ileostomy output.

DESIGN:

An institutional review board-approved, prospective clinical trial was conducted at a single institution from November 2014 through December 2015.

SETTINGS:

The study was conducted in a single, large academic medical center.

PATIENTS:

Patients >18 years of age undergoing surgery with plans for ileostomy were eligible.

INTERVENTIONS:

Televideoconference assessments of ileostomy output and the need for medical intervention were conducted during the postoperative stay and compared with in-person assessment.

MAIN OUTCOME MEASURES:

The primary end point of the trial was the feasibility of using teleconferencing to assess the need for medical intervention, defined as 90% agreement between telemedicine and in-person assessments. Secondary end points included patient/provider satisfaction, and correlative studies examined dehydration events and readmission.

RESULTS:

Twenty-seven patients underwent 44 teleconferencing assessments of ileostomy output. Compared with in-person treatment decisions, there was a 95% match (95% CI, 85%–99%). The readmission rate for the study participants was 31%, and 18% experienced dehydration events. Both patients and faculty responded favorably to surveys regarding the use of telemedicine in the perioperative period.

LIMITATIONS:

The study is limited by its in-hospital use of technology and small sample size.

CONCLUSIONS:

Televideoconference evaluation is a feasible, reliable means of assessing ileostomy output with high patient and physician acceptance. Our pilot study provides rationale for further study in the postdischarge setting for patients with ileostomies. The incorporation of televideoconference assessment within a teledischarge program may enable early intervention to improve patient outcomes. See Video Abstract at http://links.lww.com/DCR/A455.
Menopause improves the predictive value of common cardiovascular risk scores in women with premature coronary artery disease
Authors: Kryczka Karolina Ewa , Kruk Mariusz , Piotrowski Walerian , Księżycka Ewa , Pracoń Radosław , Witkowski Adam , Demkow Marcin , Lubiszewska Barbara
Published: December 2017

Objective:

Menopause, particularly its early stage (≤3 years from onset), may be an important risk factor for premature coronary artery disease. The objective of the study was to assess whether the addition of the presence of menopause in women with premature coronary artery disease could improve the predictive value of the Atherosclerotic Cardiovascular Disease risk estimator and the Systematic COronary Risk Evaluation model.

Methods:

The case-control study included 307 women with coronary artery disease aged 55 or less, and 347 age-matched controls without coronary artery disease. Diagnostic accuracy parameters were evaluated for traditional risk models versus those enriched with menopausal status. Early and late postmenopausal periods were defined as ≤3 and >3 years from the onset of menopause, respectively.

Results:

Only the addition of the presence of the early postmenopausal stage to the 10-year Atherosclerotic Cardiovascular Disease risk classes resulted in significantly increased c-statistics from 0.66 (95% confidence interval [CI] 0.62-0.7) to 0.705 (95%CI 0.66-0.75) (P = 0.0003) and an increase of accuracy from 61.3% to 63.8% (P = 0.0025).

Adding the presence of early postmenopause to the Systematic COronary Risk Evaluation risk classes also resulted in significantly increased c-statistics from 0.59 (95% CI 0.55-0.63) to 0.641 (95%CI 0.6-0.68) (P = 0.0024) and an increase of accuracy from 64.1% versus 57.5% (P = 0.001).

Conclusion:

Adding the early menopausal period may significantly improve the predictive value of the 10-year Atherosclerotic Cardiovascular Disease risk score and the Systematic COronary Risk Evaluation model in women with premature coronary artery disease.
Vasomotor symptom characteristics: are they risk factors for incident diabetes?
Authors: Gray Kristen E. , Katon Jodie G. , LeBlanc Erin S. , Woods Nancy F. , Bastian Lori A. , Reiber Gayle E. , Weitlauf Julie C. , Nelson Karin M. , LaCroix Andrea Z.
Published: December 2017

Objective:

Vasomotor symptoms (VMS), encompassing hot flashes and night sweats, may be associated with diabetes, but evidence is limited. We sought to estimate these associations.

Methods:

Among 150,007 postmenopausal Women's Health Initiative participants from 1993 to 2014, we prospectively examined associations of incident diabetes with VMS characteristics at enrollment: any VMS, severity (mild/ moderate/severe), type (hot flashes/night sweats), timing (early [premenopausal or perimenopausal]/late [postmenopausal]), and duration. Cox proportional-hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs).

Results:

Mean duration of follow-up was 13.1 years. VMS prevalence was 33%. Reporting any VMS was associated with 18% increased diabetes risk (95% CI 1.14, 1.22), which increased with severity (mild: HR 1.13, 95% CI 1.08, 1.17; moderate: HR 1.29, 95% CI 1.22, 1.36; severe: HR 1.48, 95% CI 1.34, 1.62) and duration (4% per 5 years, 95% CI 1.03, 1.05), independent of obesity. Diabetes risk was more pronounced for women reporting any night sweats (night sweats only: HR 1.20, 95% CI 1.13, 1.26; night sweats and hot flashes: HR 1.22, 95% CI 1.17, 1.27) than only hot flashes (HR 1.08, 95% CI 1.02, 1.15) and was restricted to late VMS (late: HR 1.12, 95% CI 1.07, 1.18; early and late: HR 1.16, 95% CI 1.11, 1.22; early: HR 0.99, 95% CI 0.95, 1.04).

Conclusions:

VMS are associated with elevated diabetes risk, particularly for women reporting night sweats and postmenopausal symptoms. The menopause transition may be an optimal window for clinicians to discuss long-term cardiovascular/metabolic risk with patients and leverage the bother of existing symptoms for behavior change to improve VMS and reduce diabetes risk.
Trauma exposure and endothelial function among midlife women
Authors: Thurston Rebecca C. , Barinas-Mitchell Emma , von Känel Roland , Chang Yuefang , Koenen Karestan C. , Matthews Karen A.
Published: December 2017

Objective:

Trauma is a potent exposure that can have implications for health. However, little research has considered whether trauma exposure is related to endothelial function, a key process in the pathophysiology of cardiovascular disease (CVD). We tested whether exposure to traumatic experiences was related to poorer endothelial function among midlife women, independent of CVD risk factors, demographic factors, psychosocial factors, or a history of childhood abuse.

Methods:

In all, 272 nonsmoking perimenopausal and postmenopausal women aged 40 to 60 years without clinical CVD completed the Brief Trauma Questionnaire, the Child Trauma Questionnaire, physical measures, a blood draw, and a brachial ultrasound for assessment of brachial artery flow-mediated dilation (FMD). Relations between trauma and FMD were tested in linear regression models controlling for baseline vessel diameter, demographics, depression/anxiety, CVD risk factors, health behaviors, and, additionally, a history of childhood abuse.

Results:

Over 60% of the sample had at least one traumatic exposure, and 18% had three or more exposures. A greater number of traumatic exposures was associated with lower FMD, indicating poorer endothelial function in multivariable models (beta, β [standard error, SE] −1.05 [0.40], P = 0.01). Relations between trauma exposure and FMD were particularly pronounced for three or more trauma exposures (b [SE] −1.90 [0.71], P = 0.008, relative to no exposures, multivariable).

Conclusions:

A greater number of traumatic exposures were associated with poorer endothelial function. Relations were not explained by demographics, CVD risk factors, mood/anxiety, or a by history of childhood abuse. Women with greater exposure to trauma over life maybe at elevated CVD risk.
Severe menopausal symptoms associated with reduced adherence to antiretroviral therapy among perimenopausal and menopausal women living with HIV in Metro Vancouver
Authors: Duff Putu K. , Money Deborah M. , Ogilvie Gina S. , Ranville Florence , Kestler Mary , Braschel Melissa C. , Pick Neora , Shannon Kate
Published: December 2017

Objectives:

Although more women living with HIV (WLWH) are entering midlife, the experiences of perimenopausal and menopausal WLWH, including the effects of menopausal symptoms severity, remain understudied. This study longitudinally investigated the correlates of antiretroviral therapy (ART) adherence among perimenopausal and menopausal WLWH from Metro Vancouver.

Methods:

Analyses drew on longitudinal data (2014-2017) from Sexual health and HIV/AIDS: Women's Longitudinal Needs Assessment, an ongoing community-based cohort of WLWH, aged 14+, from Metro Vancouver, Canada. At baseline and biannually, participants completed an interviewer-administered questionnaire. Bivariate and multivariable logistic regression with generalized estimating equations were used to identify the correlates of self-reported <95% ART adherence.

Results:

The sample included 109 perimenopausal and menopausal WLWH (233 observations), with a median age of 49 years (IQR 44-53). Whereas most (68.8%) participants experienced menopausal symptoms, only 17% had received treatment (eg, antidepressants, hormone therapy) at baseline. In multivariable analysis, severe menopausal symptoms (adjusted odds ratio [AOR] 1.03, 95% confidence interval [CI] 1.00-1.06), injection drug use (AOR 2.86, 95% CI 1.44-5.55), and physical/sexual violence (AOR 2.33, 95% CI 1.02-5.26) independently and positively correlated with <95% adherence.

Conclusions:

These findings suggest that menopausal symptoms may undermine ART adherence, with overlapping vulnerabilities such as injection drug use and sexual/physical violence further exacerbating poor ART adherence. Women-centred, trauma-informed care approaches to detect menopause and treat menopausal symptoms are urgently needed. Such approaches should holistically address the intersecting barriers to adherence and link WLWH to peripheral health and social services, including trauma counseling and evidence-based harm reduction services.
Safety and Efficacy of Atazanavir Powder and Ritonavir in HIV-1-Infected Infants and Children From 3 Months to <11 Years of Age
Authors: Cotton Mark F. , Liberty Afaaf , Torres-Escobar Indiana , Gonzalez-Tome Maria Isabel , Lissens Jurgen , Zaru Luna , Klauck Isabelle , Cambilargiu Daniela , Pikora Cheryl , Correll Todd A.
Published: December 2017

Background:

Novel antiretroviral formulations that are palatable, safe, and effective are needed for infants and children.

Methods:

PRINCE-2 is an ongoing clinical trial assessing safety, efficacy, and palatability of once-daily atazanavir powder formulation boosted with ritonavir (ATV + RTV) plus optimized dual nucleos(t)ide reverse transcriptase inhibitors therapy in antiretroviral-naïve/experienced children with screening HIV-1 RNA ≥1000 copies/mL. Children 3 months to <11 years received ATV + RTV by 5 baseline weight bands: 5 to <10 kg = 150/80 mg; 5 to <10 kg = 200/80 mg; 10 to <15 kg = 200/80 mg; 15 to <25 kg = 250/80 mg; and 25 to <35 kg = 300/100 mg.

Results:

Of 99 treated children, 83.8% and 59.6% remained on ATV powder until 24 and 48 weeks, respectively. Through 48 weeks, the most common adverse events were upper respiratory tract infections (33.3%), gastroenteritis (28.3%), vomiting (21.2%) and hyperbilirubinemia (18.2%; none leading to treatment discontinuation). Serious adverse events occurred in 20.2% of patients. Laboratory grade 3–4 hyperbilirubinemia occurred in 9.2% and elevated total/pancreatic amylase in 33.7%/3.1%. At week 24, proportions with virologic suppression (HIV-1 RNA <50 copies/mL; intention-to-treat analysis) across weight bands were 10/23 (43.5%), 2/12 (16.5%), 10/21 (47.6%), 19/35 (54.3%) and 5/8 (62.5%), respectively. Virologic suppression was similar in antiretroviral-naïve/experienced patients and lowest in the 5 to <10 kg = 200/80 mg group, likely because of higher baseline HIV-1 RNA and discontinuation (66.7%). Overall, virologic suppression at weeks 24 (46.5%) and 48 (43.0%) was comparable. At week 48, 83.3% and 74.1% of caregivers reported no trouble giving ATV powder and RTV, respectively.

Conclusions:

ATV powder palatability, efficacy and lack of unexpected safety findings support its use for HIV-1-infected children ≥3 months to <11 years.
Gastritis staging as a clinical priority
Authors: Mescoli Claudia , Gallo Lopez Aly , Taxa Rojas Luis , Jove Oblitas Walker , Fassan Matteo , Rugge Massimo
Published: December 2017

The elective background for gastric adenocarcinoma is the atrophic transformation of the gastric mucosa. The extent of mucosal atrophy basically parallels the risk of developing gastric cancer. This means that either noninvasive (serology) or invasive (endoscopy/histology) methods enabling the atrophic transformation to be quantified can be used theoretically to assess a given patient’s gastric cancer risk. This review aims to focus on the reliability of histology gastritis Operative Link for Gastritis Assessment -staging system for assessing the ‘personalized’ cancer risk in individuals with (atrophic) gastritis.
Immune therapies in acute myeloid leukemia: a focus on monoclonal antibodies and immune checkpoint inhibitors
Authors: Assi Rita , Kantarjian Hagop , Ravandi Farhad , Daver Naval
Published: December 2017

Purpose of review

This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed-death 1 (PD-1).

Recent findings

The stellar success of immune therapies that harness the power of T cells in solid tumors and an improved understanding of the immune system in patients with hematologic malignancies have resulted in major efforts to develop immune therapies for the treatment of patients with AML. Monoclonal antibodies in AML therapy include naked antibodies against AML surface antigens such as CD33 (e.g. lintuzumab) or CD38 (e.g. daratumumab), antibodies conjugated to toxins in various anti-CD33 (gemtuzumab ozogamicin, SGN33A, IMGN779) and anti-CD123 (SL-401, SGN-CD123A) formulations, and antibodies conjugated to radioactive particles such as 131I or 225Ac-labeled anti-CD33 or anti-CD45 antibodies. Additional antigenic targets of interest in AML include CLL1, CD38, CD25, TIM3, FLT3, and others. Approaches to harness the body's own T cells against AML include antibodies that recruit and induce cytotoxicity of tumor cells by T cells (bispecific T-cell engager [BiTE] such as CD33 x CD3 (e.g. AMG 330) or CD123 x CD3 (e.g. flotetuzumab, JNJ-63709178) or antibodies that block immune checkpoint receptors CTLA4 (e.g. ipilimumab) or PD1/PD-L1 (e.g. nivolumab, pembrolizumab, avelumab) on T cells, unleashing the patients’ T cells against leukemic cells.

The ongoing trials and well designed correlative interrogation of the immune system in patients treated on such trials will further enhance our understanding and clinical application of immune therapies as single-agent and combination approaches for the treatment of AML.
Incidence and Predictors of Readmissions in Acute Pancreatitis
Authors: Garg Sushil Kumar , Campbell James P. , Anugwom Chimaobi , Wadhwa Vaibhav , Singh Rajeshwar , Gupta Nancy , Sanaka Madhusudhan R.
Published: December 2017

Objectives

Acute pancreatitis (AP) is a common cause for hospitalization, and readmission is common, with variable associated risk factors for readmission. Here, we assessed the incidence and risk factors for readmission in AP in a large national database.

Methods

We analyzed data from the National Readmission Database during the year 2013. Index admissions with a primary discharge diagnosis of AP using the International Classification of Diseases, Ninth Revision, Clinical Modification were identified from January to November to identify 30-day readmission rates. Demographic, hospital, and clinical diagnoses were included in multivariate regression analysis to identify readmission risk factors.

Results

We identified 243,816 index AP discharges with 39,623 (16.2%) readmitted within 30 days. The most common reason for readmission was recurrent AP (41.5%). Increased odds of all-cause readmission were associated with younger age, nonhome discharge, increasing Charlson Comorbidity Index, and increased length of stay. Cholecystectomy during index admission was associated with reduced all-cause and recurrent AP readmissions (odds ratios of 0.5, and 0.35, respectively).

Conclusions

Readmission for AP is common, most often due to recurrent AP. Multiple factors, including cholecystectomy, during index admission, are associated with significantly reduced odds of all-cause and recurrent AP readmissions.