bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracting genetic alteration information for personalized cancer therapy from ClinicalTrials.gov
Authors: Xu Jun , Lee Hee-Jin , Zeng Jia , Wu Yonghui , Zhang Yaoyun , Huang Liang-Chin , Johnson Amber , Holla Vijaykumar , Bailey Ann M , Cohen Trevor , Meric-Bernstam Funda , Bernstam Elmer V , Xu Hua 
Published: June 2016

Abstract
Objective: Clinical trials investigating drugs that target specific genetic alterations in tumors are important for promoting personalized cancer therapy. The goal of this project is to create a knowledge base of cancer treatment trials with annotations about genetic alterations from ClinicalTrials.gov.
Methods: We developed a semi-automatic framework that combines advanced text-processing techniques with manual review to curate genetic alteration information in cancer trials. The framework consists of a document classification system to identify cancer treatment trials from ClinicalTrials.gov and an information extraction system to extract gene and alteration pairs from the Title and Eligibility Criteria sections of clinical trials. By applying the framework to trials at ClinicalTrials.gov, we created a knowledge base of cancer treatment trials with genetic alteration annotations. We then evaluated each component of the framework against manually reviewed sets of clinical trials and generated descriptive statistics of the knowledge base.
Results and Discussion: The automated cancer treatment trial identification system achieved a high precision of 0.9944. Together with the manual review process, it identified 20 193 cancer treatment trials from ClinicalTrials.gov. The automated gene-alteration extraction system achieved a precision of 0.8300 and a recall of 0.6803. After validation by manual review, we generated a knowledge base of 2024 cancer trials that are labeled with specific genetic alteration information. Analysis of the knowledge base revealed the trend of increased use of targeted therapy for cancer, as well as top frequent gene-alteration pairs of interest. We expect this knowledge base to be a valuable resource for physicians and patients who are seeking information about personalized cancer therapy.
Multimodal MRI features predict isocitrate dehydrogenase genotype in high-grade gliomas
Authors: Zhang Biqi , Chang Ken , Ramkissoon Shakti , Tanguturi Shyam , Bi Wenya Linda , Reardon David A. , Ligon Keith L. , Alexander Brian M. , Wen Patrick Y. , Huang Raymond Y. 
Published: June 2016

Abstract

Background.
High-grade gliomas with mutations in the isocitrate dehydrogenase (IDH) gene family confer longer overall survival relative to their IDH-wild-type counterparts. Accurate determination of the IDH genotype preoperatively may have both prognostic and diagnostic value. The current study used a machine-learning algorithm to generate a model predictive of IDH genotype in high-grade gliomas based on clinical variables and multimodal features extracted from conventional MRI.

Methods.
Preoperative MRIs were obtained for 120 patients with primary grades III (n = 35) and IV (n = 85) glioma in this retrospective study. IDH genotype was confirmed for grade III (32/35, 91%) and IV (22/85, 26%) tumors by immunohistochemistry, spectrometry-based mutation genotyping (OncoMap), or multiplex exome sequencing (OncoPanel). IDH1 and IDH2 mutations were mutually exclusive, and all mutated tumors were collapsed into one IDH-mutated cohort. Cases were randomly assigned to either the training (n = 90) or validation cohort (n = 30). A total of 2970 imaging features were extracted from pre- and postcontrast T1-weighted, T2-weighted, and apparent diffusion coefficient map. Using a random forest algorithm, nonredundant features were integrated with clinical data to generate a model predictive of IDH genotype.

Results.
Our model achieved accuracies of 86% (area under the curve [AUC] = 0.8830) in the training cohort and 89% (AUC = 0.9231) in the validation cohort. Features with the highest predictive value included patient age as well as parametric intensity, texture, and shape features.

Conclusion.
Using a machine-learning algorithm, we achieved accurate prediction of IDH genotype in high-grade gliomas with preoperative clinical and MRI features.
Cumulative Fluid Balance and Mortality in Septic Patients With or Without Acute Kidney Injury and Chronic Kidney Disease*
Authors: Neyra Javier A. , Li Xilong , Canepa-Escaro Fabrizio , Adams-Huet Beverley , Toto Robert D. , Yee Jerry , Hedayati S. Susan 
Published: June 2016

Objective:
Incident acute kidney injury and prevalent chronic kidney disease are commonly encountered in septic patients. We examined the differential effect of acute kidney injury and chronic kidney disease on the association between cumulative fluid balance and hospital mortality in critically ill septic patients.

Design:
Retrospective cohort study.

Setting:
Urban academic medical center ICU.

Patients:
ICU adult patients with severe sepsis or septic shock and serum creatinine measured within 3 months prior to and 72 hours of ICU admission. Patients with estimated glomerular filtration rate less than 15 mL/min/1.73 m2 or receiving chronic dialysis were excluded.

Interventions:
None.

Measurements and Main Results:
A total of 2,632 patients, 1,211 with chronic kidney disease, were followed up until hospital death or discharge. Acute kidney injury occurred in 1,525 patients (57.9%), of whom 679 (44.5%) had chronic kidney disease. Hospital mortality occurred in 603 patients (22.9%). Every 1-L increase in cumulative fluid balance at 72 hours of ICU admission was independently associated with hospital mortality in all patients (adjusted odds ratio, 1.06 [95% CI] 1.04–1.08; p < 0.001), and in each acute kidney injury/chronic kidney disease subgroup (adjusted odds ratio, 1.06 [1.03–1.09] for acute kidney injury+/chronic kidney disease+; 1.09 [1.05–1.13] for acute kidney injury–/chronic kidney disease+; 1.05 [1.03–1.08] for acute kidney injury+/chronic kidney disease–; and 1.07 [1.02–1.11] for acute kidney injury–/chronic kidney disease–). There was a significant interaction between acute kidney injury and chronic kidney disease on cumulative fluid balance (p =0.005) such that different cumulative fluid balance cut-offs with the best prognostic accuracy for hospital mortality were identified: 5.9 L for acute kidney injury+/chronic kidney disease+; 3.8 L for acute kidney injury–/chronic kidney disease+; 4.3 L for acute kidney injury+/chronic kidney disease–; and 1.5 L for acute kidney injury–/chronic kidney disease–. The addition of cumulative fluid balance to the admission Sequential Organ Failure Assessment score had increased prognostic utility for hospital mortality when compared with Sequential Organ Failure Assessment alone, particularly in patients with acute kidney injury.

Conclusions:
Higher cumulative fluid balance at 72 hours of ICU admission was independently associated with hospital mortality regardless of acute kidney injury or chronic kidney disease presence. We characterized cumulative fluid balance cut-offs associated with hospital mortality based on acute kidney injury/chronic kidney disease status, underpinning the heterogeneity of fluid regulation in sepsis and kidney disease.
Impact of Different Diagnostic Criteria on the Reported Prevalence of Junctional Ectopic Tachycardia After Pediatric Cardiac Surgery
Authors: Entenmann Andreas , Michel Miriam , Egender Friedemann , Hessling Vera , Kramer Hans-Heiner 
Published: June 2016

Objectives:
Junctional ectopic tachycardia is a frequent complication after pediatric cardiac surgery. A uniform definition of postoperative junctional ectopic tachycardia has yet to be established in the literature. The objective of this study is to analyze differences in the general and age-related prevalence of postoperative junctional ectopic tachycardia according to different diagnostic definitions.

Design:
Data files and electrocardiograms of 743 patients (age, 1 d to 17.6 yr) who underwent surgery for congenital heart disease during a 3-year period were reviewed. The prevalence of postoperative junctional ectopic tachycardia in this cohort was determined according to six different definitions identified in the literature and one definition introduced for analytical purposes. Agreement between the definitions was analyzed according to Cohen κ coefficients. A receiver operating characteristic analysis was performed to determine the ability of different definitions to discriminate between patients with increased postoperative morbidity and without.

Setting:
A university-affiliated tertiary pediatric cardiac PICU.

Patients:
Infants and children who underwent heart surgery.

Interventions:
None.

Measurements and Main Results:
The prevalence of postoperative junctional ectopic tachycardia ranged from 2.0% to 8.3% according to the seven different definitions. Even among definitions for which the general prevalence was almost equal, the distribution according to age varied. Most definitions used a frequency criterion to define postoperative junctional ectopic tachycardia. Definitions based on a fixed frequency criterion did not identify cases of postoperative junctional ectopic tachycardia in patients older than 12 months. The grade of agreement was moderate or poor between definitions using a fixed or dynamic frequency criterion and those not based on a critical heart rate (κ = 0.37–0.66). In the receiver operating characteristic analysis, the definition with a fixed frequency criterion of 180 beats/min or an age-related frequency criterion according to the 95th percentile showed the optimal cut-off value to determine increased postoperative morbidity.

Conclusions:
Different definitions of junctional ectopic tachycardia after pediatric cardiac surgery lead to relevant differences in the reported prevalence and age distribution pattern. A uniform definition of postoperative junctional ectopic tachycardia is needed to provide comparable study results and to improve the diagnosis of junctional ectopic tachycardia in pediatric patients.
Two-Stage Implant-Based Breast Reconstruction: An Evolution of the Conceptual and Technical Approach over a Two-Decade Period
Authors: Cordeiro Peter G. , Jazayeri Leila 
Published: June 2016

Background:
Over a two-decade period, the senior author (P.G.C.) has had extensive experience with two-stage implant-based breast reconstruction with total musculofascial coverage. During this period, the approach has evolved substantially. The evolution has been based on changes in breast cancer treatment, available technology and, most importantly, yearly evaluation of surgical outcomes.

Methods:
This article describes changes in the conceptual approach to breast reconstruction, and the resulting evolution of surgical techniques. Evolving concepts and current techniques are described as they relate to each consecutive stage of implant-based breast reconstruction.

Results:
For the first stage of breast reconstruction (i.e., placement of the tissue expander), key concepts and techniques described are the vertical mastectomy defect, the point of maximal expansion, the musculofascial pocket, and the inferior fasciotomy. For the second stage of breast reconstruction (i.e., the exchange procedure), key concepts and techniques described are implant selection, setting the inframammary fold, defining the inferolateral shape of the breast, and circumferential capsulotomy.

Conclusion:
The purpose of this article is to relay the lessons learned from this long experience and to provide a conceptual and technical framework to two-stage implant-based breast reconstruction.
Defining the Role of Secondary Intention Healing in Full-Thickness Lid Margin Defects
Authors: Morton Jonathan David 
Published: June 2016

Summary:
More than 30 years have passed since the first case series was published regarding the phenomenon of secondary intention healing in relation to lid margin defects. Despite the fascinating results, the technique has not gained widespread support. This study looks at a series of 34 marginal lower lid defects allowed to heal without intervention. The results are remarkable for their consistently high quality, in terms of both cosmetic and functional outcomes. Medial lid defects, in particular, yielded results that would be difficult to surpass by conventional reconstructive techniques. The evidence presented here shows that secondary intention healing in lid margin defects should be considered as a genuine alternative to formal reconstruction, challenging the established dogma of bilamellar repair. For certain lid defects it is quite possibly (and unexpectedly) the new treatment of choice.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Proposal of the TBN Classification of Thoracic Anomalies and Treatment Algorithm for Poland Syndrome
Authors: Romanini Maria Victoria , Torre Michele , Santi Pierluigi , Dova Laura , Valle Maura , Martinoli Carlo , Baldelli Iaria 
Published: June 2016

Background:
Poland syndrome is a congenital deformity characterized by unilateral anomalies of pectoralis muscles, breast, nipple, axillary fold, subcutaneous tissue, ribs, and upper limb. The thoracic anomaly, which is the pathognomonic malformation of Poland syndrome, presents a wide phenotype variability and has been classified by different authors. However, these classifications do not include all the possible phenotypes of Poland syndrome. The aim of this study is to propose a simple classification of the whole spectrum of thoracic anomalies and a treatment algorithm that could have a practical value for determining the surgical approach.

Methods:
Since 2008, 100 patients have been evaluated by the same plastic surgical team at San Martino Hospital-IST and Istituto Gaslini of Genoa, Italy, using the thorax, breast, nipple-areola complex (TBN) classification. Thoracic anomalies were classified as follows: thorax (T), from T1 (muscle defect only) to T4 (complex deformity with rib and sternal involvement); breast (B), in B1 (hypoplasia) or B2 (amastia); and nipple-areola complex (N), from N1 (dislocation <2 cm) to N3 (athelia).

Results:
The most frequent thoracic anomalies were T1 (47 percent) and N2 (74 percent), whereas in female patients, B1 was more frequent than B2. The surgical approach to breast and pectoral reconstruction was based not only on the patient’s age and sex, but also on the type of anomaly according to the TBN classification. In particular, a two-step approach with tissue expanders was required in N2 and N3 cases, whereas in N1 patients a single step was sufficient.

Conclusion:
The TBN classification can be a useful tool for surgical decision-making according to each specific thoracic anomaly.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Diagnostic, IV.
Periorbital and Orbital Aging: Senile Enophthalmos as a Cause of Upper Eyelid Ptosis
Authors: Guyuron Bahman , Harvey Donald 
Published: June 2016

Background:
The aim of this study was to assess the effects of orbital aging over a prolonged period.

Methods:
The orbit and periorbital region were assessed in 21 adult patients over 6 to 24 years with medical-quality facial photographs. The anteroposterior and lateral photographs were evaluated for orbital changes, including enophthalmos and upper eyelid position. Quantitative analysis was performed on the anteroposterior photographs, and qualitative analysis was used to assess enophthalmos.

Results:
The mean age of the patients was 40 years at initial photography and 57 years at the time of secondary photography. At initial photography, eight of the 21 patients had ptosis: six had bilateral mild ptosis (<2 mm), one had bilateral moderate (2 to 3 mm) ptosis, and one had unilateral mild ptosis. At the second time point, only two patients did not have ptosis: four had unilateral mild, seven had bilateral mild, and eight had bilateral moderate ptosis. One patient had unilateral and two patients had bilateral enophthalmos at the initial photography. Nineteen of the 21 patients had relative enophthalmos at the second time point, and all 19 of the patients had eyelid ptosis (p < 0.00001).

Conclusions:
This study demonstrates the development of age-related enophthalmos and eyelid ptosis and the strong association between age-related enophthalmos and upper eyelid ptosis, which is commonly undetected.
Mid-Term Dental and Nerve-Related Complications of Infant Distraction for Robin Sequence
Authors: Steinberg Jordan P. , Brady Colin M. , Waters Brittany R. , Soldanska Magdalena , Burstein Fernando D. , Thomas Jack E. , Williams Joseph K. 
Published: June 2016

Background:
Mandibular distraction is effective for relieving airway obstruction in Robin sequence; however, mid-term dental and nerve-related complications have not been adequately studied.

Methods:
Records were reviewed for patients with a single distraction in infancy using internal devices. Follow-up was 5 years or longer. Craniofacial dysmorphic syndromes and those affecting facial nerve function were excluded. Part I involved a review of dental records, whereas Part II involved assessment of inferior alveolar and marginal mandibular nerve function in returning patients with the use of 1,1,1,2-tetrafluoroethane cold stimulation and photography, respectively.

Results:
Eighty-five patients met inclusion criteria. Dental records were complete in 44 patients (median follow-up, 7.3 years; range, 5.4 to 13.2 years). First permanent molar injury was seen in 42 of 88 half-mouths (48 percent); 32 of 42 (76 percent) were restorable. Primary second molar damage and ankylosis were observed in 12 of 88 (14 percent) and one of 88 half-mouths (1 percent), respectively. Mandibular second premolar absence was noted unilaterally in eight of 36 patients (22 percent) and bilaterally in six of 36 patients (17 percent). A mean 1.2 ± 0.95 operative rehabilitations were required. Nerve testing was completed in 20 patients (median follow-up, 8.7 years; range, 5.5 to 13.2 years). Complete absence of cold sensation was noted in one of 40 half-mouths (2.5 percent), whereas lower lip depressor weakness was seen in six of 40 half-mouths (15 percent).

Conclusions:
Infant distraction is highly successful in averting tracheostomy; however, dental and nerve-related complications remain underreported. Regular follow-up with a pediatric dentist and early recognition of injury is essential. Although inferior alveolar nerve injury appears infrequent (2.5 percent), permanent lower lip depressor weakness is more common than previously reported (15 percent of sides).

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Peripheral Motor and Sensory Nerve Conduction following Transplantation of Undifferentiated Autologous Adipose Tissue–Derived Stem Cells in a Biodegradable U.S. Food and Drug Administration–Approved Nerve Conduit
Authors: Klein Silvan M. , Vykoukal Jody , Li De-Pei , Pan Hui-Lin , Zeitler Katharina , Alt Eckhard , Geis Sebastian , Felthaus Oliver , Prantl Lukas 
Published: June 2016

Background:
Conduits preseeded with either Schwann cells or stem cells differentiated into Schwann cells demonstrated promising results for the outcome of nerve regeneration in nerve defects.

Methods:
The concept of this trial combines nerve repair by means of a commercially available nerve guidance conduit and preseeding with autologous, undifferentiated, adipose tissue-derived stem cells. Adipose tissue-derived stem cells were harvested from rats and subsequently seeded onto a U.S. Food and Drug Administration–approved type I collagen conduit. Sciatic nerve gaps 10 mm in length were created, and nerve repair was performed by the transplantation of either conduits preseeded with autologous adipose tissue-derived stem cells or acellular (control group) conduits. After 6 months, the motor and sensory nerve conduction velocity were assessed. Nerves were removed and examined by hematoxylin and eosin, van Gieson, and immunohistochemistry (S100 protein) staining for the quality of axonal regeneration.

Results:
Nerve gaps treated with adipose tissue-derived stem cells showed superior nerve regeneration, reflected by higher motor and sensory nerve conduction velocity values. The motor and sensory nerve conduction velocity were significantly greater in nerves treated with conduits preseeded with adipose tissue-derived stem cells than in nerves treated with conduits alone (p < 0.05). Increased S100 immunoreactivity was detected for the adipose tissue-derived stem cell group. In this group, axon arrangement inside the conduits was more organized.

Conclusions:
Transplantation of adipose tissue-derived stem cells significantly improves motor and sensory nerve conduction velocity in peripheral nerve gaps. Preseeded conduits showed a more organized axon arrangement inside the conduit in comparison with nerve conduits alone. The approach used here could readily be translated into a clinical therapy.

CLINCAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, V.
Why re-entrant surface topography is needed for robust oleophobicity
Authors: Nosonovsky Michael , Bhushan Bharat 
Published: June 2016

Surface patterns affect wetting properties of solid materials allowing manipulation of the phase state of an adjacent fluid. The best known example of this effect is the superhydrophobic composite (Cassie–Baxter) interface with vapour/air pockets between the solid and liquid. Mathematically, the effect of surface micropatterns can be studied by an averaging technique similarly to the method of separation of motions in dynamics. However, averaged parameters are insufficient for robust superhydrophobic and superoleophobic surfaces because additional topography features are important: hierarchical organization and re-entrant roughness. The latter is crucial for the oleophobicity because it enhances the stability of a composite interface. The re-entrant topography can be achieved by various methods. Understanding the role of re-entrant surface topography gives us new insights on the multitude of wetting scenarios beyond the standard Wenzel and Cassie–Baxter models.
This article is part of the themed issue ‘Bioinspired hierarchically structured surfaces for green science’.
Superhydrophobic hierarchically structured surfaces in biology: evolution, structural principles and biomimetic applications
Authors: Barthlott W. , Mail M. , Neinhuis C. 
Published: June 2016

A comprehensive survey of the construction principles and occurrences of superhydrophobic surfaces in plants, animals and other organisms is provided and is based on our own scanning electron microscopic examinations of almost 20 000 different species and the existing literature. Properties such as self-cleaning (lotus effect), fluid drag reduction (Salvinia effect) and the introduction of new functions (air layers as sensory systems) are described and biomimetic applications are discussed: self-cleaning is established, drag reduction becomes increasingly important, and novel air-retaining grid technology is introduced. Surprisingly, no evidence for lasting superhydrophobicity in non-biological surfaces exists (except technical materials). Phylogenetic trees indicate that superhydrophobicity evolved as a consequence of the conquest of land about 450 million years ago and may be a key innovation in the evolution of terrestrial life. The approximate 10 million extant species exhibit a stunning diversity of materials and structures, many of which are formed by self-assembly, and are solely based on a limited number of molecules. A short historical survey shows that bionics (today often called biomimetics) dates back more than 100 years. Statistical data illustrate that the interest in biomimetic surfaces is much younger still. Superhydrophobicity caught the attention of scientists only after the extreme superhydrophobicity of lotus leaves was published in 1997. Regrettably, parabionic products play an increasing role in marketing.This article is part of the themed issue ‘Bioinspired hierarchically structured surfaces for green science’.