bluuebunny/crossref_metadata_2025_split huggingface dataset:
iCFN: an efficient exact algorithm for multistate protein design
Authors: Karimi Mostafa , Shen Yang 
Published: July 2018

Abstract

Motivation
Multistate protein design addresses real-world challenges, such as multi-specificity design and backbone flexibility, by considering both positive and negative protein states with an ensemble of substates for each. It also presents an enormous challenge to exact algorithms that guarantee the optimal solutions and enable a direct test of mechanistic hypotheses behind models. However, efficient exact algorithms are lacking for multistate protein design.

Results
We have developed an efficient exact algorithm called interconnected cost function networks (iCFN) for multistate protein design. Its generic formulation allows for a wide array of applications such as stability, affinity and specificity designs while addressing concerns such as global flexibility of protein backbones. iCFN treats each substate design as a weighted constraint satisfaction problem (WCSP) modeled through a CFN; and it solves the coupled WCSPs using novel bounds and a depth-first branch-and-bound search over a tree structure of sequences, substates, and conformations. When iCFN is applied to specificity design of a T-cell receptor, a problem of unprecedented size to exact methods, it drastically reduces search space and running time to make the problem tractable. Moreover, iCFN generates experimentally-agreeing receptor designs with improved accuracy compared with state-of-the-art methods, highlights the importance of modeling backbone flexibility in protein design, and reveals molecular mechanisms underlying binding specificity.

Availability and implementation
https://shen-lab.github.io/software/iCFN

Supplementary information
Supplementary data are available at Bioinformatics online.
Clinical applications of machine learning in cardiovascular disease and its relevance to cardiac imaging
Authors: Al’Aref Subhi J , Anchouche Khalil , Singh Gurpreet , Slomka Piotr J , Kolli Kranthi K , Kumar Amit , Pandey Mohit , Maliakal Gabriel , van Rosendael Alexander R , Beecy Ashley N , Berman Daniel S , Leipsic Jonathan , Nieman Koen , Andreini Daniele , Pontone Gianluca , Schoepf U Joseph , Shaw Leslee J , Chang Hyuk-Jae , Narula Jagat , Bax Jeroen J , Guan Yuanfang , Min James K 
Published: July 2018

Abstract
Artificial intelligence (AI) has transformed key aspects of human life. Machine learning (ML), which is a subset of AI wherein machines autonomously acquire information by extracting patterns from large databases, has been increasingly used within the medical community, and specifically within the domain of cardiovascular diseases. In this review, we present a brief overview of ML methodologies that are used for the construction of inferential and predictive data-driven models. We highlight several domains of ML application such as echocardiography, electrocardiography, and recently developed non-invasive imaging modalities such as coronary artery calcium scoring and coronary computed tomography angiography. We conclude by reviewing the limitations associated with contemporary application of ML algorithms within the cardiovascular disease field.
Mahalanobis distance informed by clustering
Authors: Lahav Almog , Talmon Ronen , Kluger Yuval 
Published: July 2018

AbstractA fundamental question in data analysis, machine learning and signal processing is how to compare between data points. The choice of the distance metric is specifically challenging for high-dimensional data sets, where the problem of meaningfulness is more prominent (e.g. the Euclidean distance between images). In this paper, we propose to exploit a property of high-dimensional data that is usually ignored, which is the structure stemming from the relationships between the coordinates. Specifically, we show that organizing similar coordinates in clusters can be exploited for the construction of the Mahalanobis distance between samples. When the observable samples are generated by a nonlinear transformation of hidden variables, the Mahalanobis distance allows the recovery of the Euclidean distances in the hidden space. We illustrate the advantage of our approach on a synthetic example where the discovery of clusters of correlated coordinates improves the estimation of the principal directions of the samples. Our method was applied to real data of gene expression for lung adenocarcinomas (lung cancer). By using the proposed metric we found a partition of subjects to risk groups with a good separation between their Kaplan–Meier survival plot.
Strong convergence rates of semidiscrete splitting approximations for the stochastic Allen–Cahn equation
Authors: Bréhier Charles-Edouard , Cui Jianbo , Hong Jialin 
Published: July 2018

Abstract
This article analyses an explicit temporal splitting numerical scheme for the stochastic Allen–Cahn equation driven by additive noise in a bounded spatial domain with smooth boundary in dimension $d\leqslant 3$. The splitting strategy is combined with an exponential Euler scheme of an auxiliary problem. When $d=1$ and the driving noise is a space–time white noise we first show some a priori estimates of this splitting scheme. Using the monotonicity of the drift nonlinearity we then prove that under very mild assumptions on the initial data this scheme achieves the optimal strong convergence rate $\mathcal{O}(\delta t^{\frac 14})$. When $d\leqslant 3$ and the driving noise possesses some regularity in space we study exponential integrability properties of the exact and numerical solutions. Finally, in dimension $d=1$, these properties are used to prove that the splitting scheme has a strong convergence rate $\mathcal{O}(\delta t)$.
Classic Papers Revisited: An Early Study of Cardioprotection by Volatile Anesthetics
Authors: Warltier David C. 
Published: July 2018

Abstract
Recovery of Contractile Function of Stunned Myocardium in Chronically Instrumented Dogs Is Enhanced by Halothane or Isoflurane. By Warltier DC, al-Wathiqui MH, Kampine JP, and Schmeling WT. Anesthesiology 1988; 69:552–65. Reprinted with permission.
Following brief periods (5–15 min) of total coronary artery occlusion and subsequent reperfusion, despite an absence of tissue necrosis, a decrement in contractile function of the postischemic myocardium may nevertheless be present for prolonged periods. This has been termed “stunned” myocardium to differentiate the condition from ischemia or infarction. Because the influence of volatile anesthetics on the recovery of postischemic, reperfused myocardium has yet to be studied, the purpose of this investigation was to compare the effects of halothane and isoflurane on systemic and regional hemodynamics following a brief coronary artery occlusion and reperfusion. Nine groups comprising 79 experiments were completed in 42 chronically instrumented dogs. In awake, unsedated dogs a 15-min coronary artery occlusion resulted in paradoxical systolic lengthening in the ischemic zone. Following reperfusion active systolic shortening slowly returned toward control levels but remained approximately 50% depressed from control at 5 h. In contrast, dogs anesthetized with halothane or isoflurane (2% inspired concentration) demonstrated complete recovery of function 3–5 h following reperfusion. Because the anesthetics directly depressed contractile function, additional experiments were conducted in which a 15-minute coronary artery occlusion was produced during volatile anesthesia; however, each animal was allowed to emerge from the anesthetized state at the onset of reperfusion. Similar results were obtained in these experiments, demonstrating total recovery of contractile function within 3–5 h following reperfusion. Thus, despite comparable degrees of contractile dysfunction during coronary artery occlusion in awake and anesthetized dogs, the present results demonstrate that halothane and isoflurane produce marked improvement in the recovery of segment function following a transient ischemic episode. Therefore, volatile anesthetics may attenuate postischemic left ventricular dysfunction occurring intraoperatively and enhance recovery of regional wall motion abnormalities during reperfusion.
Surgical Technique: Achieving Reduction With Temporizing, Knee-Spanning External Fixation
Authors: Liskutin Tomas , Bernstein Mitchell , Lack William , Perry Michael , Summers Hobie 
Published: July 2018

Introduction:
Peri- and intra-articular fractures about the knee are frequently managed with joint-spanning external fixation before definitive treatment. With a systematic approach, a near-anatomic reduction with respect to length, alignment, and rotation can be obtained.

Methods:
This video highlights 2 clinical cases: a bicondylar tibial plateau fracture-dislocation and a distal femur fracture, both of which were treated with temporizing, knee-spanning external fixation.

Results:
The indications, principles, and biomechanics of knee-spanning external fixation are presented. In addition, we demonstrate a systematic approach to applying knee-spanning external fixation.

Conclusions:
Temporizing, joint-spanning external fixation is a critical treatment modality in the orthopaedic armamentarium for managing fractures about the knee. With a systematic approach, it is possible to obtain a near-anatomic reduction with respect to length, alignment, and rotation.
Deresuscitation of Patients With Iatrogenic Fluid Overload Is Associated With Reduced Mortality in Critical Illness*
Authors: Silversides Jonathan A. , Fitzgerald Emma , Manickavasagam Uma S. , Lapinsky Stephen E. , Nisenbaum Rosane , Hemmings Noel , Nutt Christopher , Trinder T. John , Pogson David G. , Fan Eddy , Ferguson Andrew J. , McAuley Daniel F. , Marshall John C. 
Published: July 2018

Objectives:
To characterize current practice in fluid administration and deresuscitation (removal of fluid using diuretics or renal replacement therapy), the relationship between fluid balance, deresuscitative measures, and outcomes and to identify risk factors for positive fluid balance in critical illness.

Design:
Retrospective cohort study.

Setting:
Ten ICUs in the United Kingdom and Canada.

Patients:
Adults receiving invasive mechanical ventilation for a minimum of 24 hours.

Interventions:
None.

Measurements and Main Results:
Four-hundred patients were included. Positive cumulative fluid balance (fluid input greater than output) occurred in 87.3%: the largest contributions to fluid input were from medications and maintenance fluids rather than resuscitative IV fluids. In a multivariate logistic regression model, fluid balance on day 3 was an independent risk factor for 30-day mortality (odds ratio 1.26/L [95% CI, 1.07–1.46]), whereas negative fluid balance achieved in the context of deresuscitative measures was associated with lower mortality. Independent predictors of greater fluid balance included treatment in a Canadian site.

Conclusions:
Fluid balance is a practice-dependent and potentially modifiable risk factor for adverse outcomes in critical illness. Negative fluid balance achieved with deresuscitation on day 3 of ICU stay is associated with improved patient outcomes. Minimization of day 3 fluid balance by limiting maintenance fluid intake and drug diluents, and using deresuscitative measures, represents a potentially beneficial therapeutic strategy which merits investigation in randomized trials.
Methodologic Innovation in Creating Clinical Practice Guidelines: Insights From the 2018 Society of Critical Care Medicine Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption Guideline Effort
Authors: Devlin John W. , Skrobik Yoanna , Rochwerg Bram , Nunnally Mark E. , Needham Dale M. , Gelinas Celine , Pandharipande Pratik P. , Slooter Arjen J. C. , Watson Paula L. , Weinhouse Gerald L. , Kho Michelle E. , Centofanti John , Price Carrie , Harmon Lori , Misak Cheryl J. , Flood Pamela D. , Alhazzani Waleed 
Published: July 2018

Objectives:
To describe novel guideline development strategies created and implemented as part of the Society of Critical Care Medicine’s 2018 clinical practice guidelines for pain, agitation (sedation), delirium, immobility (rehabilitation/mobility), and sleep (disruption) in critically ill adults.

Design:
We involved critical illness survivors from start to finish, used and expanded upon Grading of Recommendations, Assessment, Development and Evaluation methodology for making recommendations, identified evidence gaps, and developed communication strategies to mitigate challenges.

Setting/Subjects:
Thirty-two experts from five countries, across five topic-specific sections; four methodologists, two medical librarians, four critical illness survivors, and two Society of Critical Care Medicine support staff.

Interventions:
Unique approaches included the following: 1) critical illness survivor involvement to help ensure patient-centered questions and recommendations; 2) qualitative and semiquantitative approaches for developing descriptive statements; 3) operationalizing a three-step approach to generating final recommendations; and 4) systematic identification of evidence gaps.

Measurements and Main Results:
Critical illness survivors contributed to prioritizing topics, questions, and outcomes, evidence interpretation, recommendation formulation, and article review to ensure that their values and preferences were considered in the guidelines. Qualitative and semiquantitative approaches supported formulating descriptive statements using comprehensive literature reviews, summaries, and large-group discussion. Experts (including the methodologists and guideline chairs) developed and refined guideline recommendations through monthly topic-specific section conference calls. Recommendations were precirculated to all members, presented to, and vetted by, most members at a live meeting. Final electronic voting provided links to all forest plots, evidence summaries, and “evidence to decision” frameworks. Written comments during voting captured dissenting views and were integrated into evidence to decision frameworks and the guideline article. Evidence gaps, reflecting clinical uncertainty in the literature, were identified during the evidence to decision process, live meeting, and voting and formally incorporated into all written recommendation rationales. Frequent scheduled “check-ins” mitigated communication gaps.

Conclusions:
Our multifaceted, interdisciplinary approach and novel methodologic strategies can help inform the development of future critical care clinical practice guidelines.
Educational Analytics
Authors: Roche Cathy C. , Wingo Nancy P. , Westfall Andrew O. , Azuero Andres , Dempsey Donald M. , Willig James H. 
Published: July 2018

To determine the effects of gamification on student education, researchers implemented “Kaizen,” a software-based knowledge competition, among a first-year class of undergraduate nursing students. Multiple-choice questions were released weekly or biweekly during two rounds of play. Participation was voluntary, and students could play the game using any Web-enabled device. Analyses of data generated from the game included (1) descriptive, (2) logistic regression modeling of factors associated with user attrition, (3) generalized linear mixed model for retention of knowledge, and (4) analysis of variance of final examination performance by play styles. Researchers found a statistically significant increase in the odds of a correct response (odds ratio, 1.8; 95% confidence interval, 1.0–3.4) for a round 1 question repeated in round 2, suggesting retention of knowledge. They also found statistically significant differences in final examination performance among different play styles.
To maximize the benefits of gamification, researchers must use the resulting data both to power educational analytics and to inform nurse educators how to enhance student engagement, knowledge retention, and academic performance.
Public Perception of Ethical Issues in Dermatology: Evidenced by New York Times Commenters
Authors: Martin Elise , Huang William W. , Strowd Lindsay C. , Hinkel Victoria S. , Feldman Steven R. , Williford Phillip M. 
Published: July 2018

BACKGROUND
A 2017 New York Times (NYT) article questioning the appropriateness of skin cancer treatment modality by dermatology providers stimulated discussion among the public pertaining to ethics in the current state of dermatologic practice.

OBJECTIVE
The purpose of this study is to characterize issues raised by the comments on the NYT article, discuss strategies to address these concerns, and encourage reflection on ethics in dermatologic care.

MATERIALS AND METHODS
A qualitative analysis was performed on the 309 comments on the NYT article. General themes were identified, resulting in the inclusion of 222 comments. These comments were reviewed and characterized by the type of commenter, his or her stance on health care, and what issues they raised.

RESULTS
Providers interested in “profit over patient” was the most common theme, followed by mistrust of APPs, health care system interested in “profit over patient,” inadequate supervision by advanced practice providers (APPs), finding the “right” provider, support for coordinated APP and physician care, support for APP credentials, and finally inappropriate elderly care.

CONCLUSION
The NYT article raises the concern of identifying quality care and choosing the “right provider”—one who successfully balances the various incentives affecting skin cancer management including appropriate usage of APPs.
Ammonia, ammonium, and the risk of asthma: A register-based case–control study in Danish children
Authors: Holst Gitte , Thygesen Malene , Pedersen Carsten B. , Peel Robert G. , Brandt Jørgen , Christensen Jesper H. , Bønløkke Jakob H. , Hertel Ole , Sigsgaard Torben 
Published: July 2018

Background:
Evidence concerning the health effects of exposure to fine particulate matter less than 2.5 μm in diameter (PM2.5) and particulate components such as ammonium (NH4
+) is limited. We aimed to investigate gaseous ammonia (NH3), particulate ammonium (NH4
+), the total concentration of these pollutants (NHx), and PM2.5 and their association with asthma in Danish preschool children.

Methods:
Estimates of incidence rate ratios associated with exposure to air pollution were calculated for children followed for the development of childhood asthma (n = 335,629) from their first to their sixth birthday during the time period 2006–2012 using a time-matched case–control design by combining register information. Modeled average concentrations of NH3, NH4
+, NHx, and PM2.5 (5.56 km × 5.56 km grid resolution) during the past 3 months prior to the date of first diagnosis of asthma for cases.

Results:
We identified 12,935 incident cases of asthma. The base adjusted hazard ratio of incident asthma was 1.74 for children exposed to the highest decile of NH3 exposure (95% confidence interval = 1.60, 1.89) compared to children exposed to the lowest decile of NH3 exposure during the past 3 months prior to first diagnosis. Similar hazard ratios were found for the highest levels of NH4
+ (2.33; 2.04, 2.65) and NHx (1.82; 1.68, 1.96). The positive associations were slightly attenuated, when adjusting for socioeconomic status, but disappeared when additionally adjusting for region, except in a two-pollutant model including NH4
+ and PM2.5. No association was found with PM2.5. The findings were robust when using different exposure time windows.

Conclusions:
Increased NH4
+ exposure may be a risk factor for the onset of asthma in preschool children.
Complications Associated With Nasogastric Tube Placement in the Acute Phase of Stroke: A Systematic Review
Authors: Nascimento Ana , Carvalho Mariana , Nogueira Jerina , Abreu Pedro , Nzwalo Hipólito 
Published: July 2018

ABSTRACT
This systematic review explores the frequency of complications associated with nasogastric tube (NGT) placement in patients with acute stroke. The unique condition of the dysphasic, immobile, confused immunosuppressed patient who has had an acute stroke hampers any consistent inference from other neurological or nonneurological condition in which NGT placement is used. Twelve studies including 921 patients fed by NGT in the acute phase (first 4 weeks) were included in the analysis. The overall quality of the included studies was good. The main limitation was the heterogeneity and small size of most studies. The occurrence of NGT placement failure and malposition, hypoxemia, and regurgitation was addressed in the selected studies. Recurrent NGT dislodgement and a combination of tube dislodgement and blockage of the tube were the main reasons for NGT placement failure. In the absence of chronic hypoxemic pulmonary or cardiac disorders, NGT feeding was not associated with clinically significant hypoxemia in patients who have had an acute stroke. Data are scarce on the topic. Research about the frequency of local and systemic NGT complications and strategies for prevention will certainly contribute to enhance evidence-based management of dysphagia in acute stroke.
Patients' Experiences of Their Recovery Process After Minor Physical Trauma
Authors: Nasirian Sara , Fagevik Olsén Monika , Engström My 
Published: July 2018

Injuries due to trauma are the leading cause of death in Sweden among people younger than 45 years, and more than 120,000 patients were admitted to hospitals in 2014 as a result of trauma. Patients suffering from less serious physical trauma are often discharged directly from the trauma unit, commonly without any follow-up plans. There is a lack of knowledge about how these patients experience their recovery process.
Eight women and 6 men were interviewed 3 months after being directly discharged from a trauma unit. Data were analyzed using the constructive grounded theory approach.
The main finding was the core category of social support, the key to recovery. Patients' roads to recapturing their health and to recovery had several barriers, which can be clustered together to either physical or psychological symptoms that enhanced their feelings of ill health and delayed their recovery. Participants described different strategies that they used to deal with these barriers. Most important was the support of others, that is, family, social life, work, and health care (primary health care).
The participants in this study described managing the recovery process by themselves as troublesome. This is partly because they do not view themselves as healthy, as the health care providers do, and many are in need of further health care after discharge. Health care providers should give better information on the expected process of recovery and the importance of social support, as it might enable patients to better overcome physical and psychological barriers in their recovery.