bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noncontrast Computed Tomography Signs as Predictors of Hematoma Expansion, Clinical Outcome, and Response to Tranexamic Acid in Acute Intracerebral Hemorrhage
Authors: Law Zhe Kang , Ali Azlinawati , Krishnan Kailash , Bischoff Adam , Appleton Jason P. , Scutt Polly , Woodhouse Lisa , Pszczolkowski Stefan , Cala Lesley A. , Dineen Robert A. , England Timothy J. , Ozturk Serefnur , Roffe Christine , Bereczki Daniel , Ciccone Alfonso , Christensen Hanne , Ovesen Christian , Bath Philip M. , Sprigg Nikola ,   on behalf of TICH-2 Investigators
Published: November 2019

Background and Purpose—
Blend, black hole, island signs, and hypodensities are reported to predict hematoma expansion in acute intracerebral hemorrhage. We explored the value of these noncontrast computed tomography signs in predicting hematoma expansion and functional outcome in our cohort of intracerebral hemorrhage.

Methods—
The TICH-2 (Tranexamic acid for IntraCerebral Hemorrhage-2) was a prospective randomized controlled trial exploring the efficacy and safety of tranexamic acid in acute intracerebral hemorrhage. Baseline and 24-hour computed tomography scans of trial participants were analyzed. Hematoma expansion was defined as an increase in hematoma volume of >33% or >6 mL on 24-hour computed tomography. Poor functional outcome was defined as modified Rankin Scale of 4 to 6 at day 90. Multivariable logistic regression was performed to identify predictors of hematoma expansion and poor functional outcome.

Results—

Of 2325 patients recruited, 2077 (89.3%) had valid baseline and 24-hour scans. Five hundred seventy patients (27.4%) had hematoma expansion while 1259 patients (54.6%) had poor functional outcome. The prevalence of noncontrast computed tomography signs was blend sign, 366 (16.1%); black hole sign, 414 (18.2%); island sign, 200 (8.8%); and hypodensities, 701 (30.2%). Blend sign (adjusted odds ratio [aOR] 1.53 [95% CI, 1.16–2.03];
P
=0.003), black hole (aOR, 2.03 [1.34–3.08];
P
=0.001), and hypodensities (aOR, 2.06 [1.48–2.89];
P
<0.001) were independent predictors of hematoma expansion on multivariable analysis with adjustment for covariates. Black hole sign (aOR, 1.52 [1.10–2.11];
P
=0.012), hypodensities (aOR, 1.37 [1.05–1.78];
P
=0.019), and island sign (aOR, 2.59 [1.21–5.55];
P
=0.014) were significant predictors of poor functional outcome. Tranexamic acid reduced the risk of hematoma expansion (aOR, 0.77 [0.63–0.94];
P
=0.010), but there was no significant interaction between the presence of noncontrast computed tomography signs and benefit of tranexamic acid on hematoma expansion and functional outcome (
P
interaction all >0.05).

Conclusions—
Blend sign, black hole sign, and hypodensities predict hematoma expansion while black hole sign, hypodensities, and island signs predict poor functional outcome. Noncontrast computed tomography signs did not predict a better response to tranexamic acid.

Clinical Trial Registration—

URL:
https://www.isrctn.com
. Unique identifier: ISRCTN93732214.
Fully Automated Segmentation Algorithm for Hematoma Volumetric Analysis in Spontaneous Intracerebral Hemorrhage
Authors: Ironside Natasha , Chen Ching-Jen , Mutasa Simukayi , Sim Justin L. , Marfatia Saurabh , Roh David , Ding Dale , Mayer Stephan A. , Lignelli Angela , Connolly Edward Sander 
Published: November 2019

Background and Purpose—
Hematoma volume measurements influence prognosis and treatment decisions in patients with spontaneous intracerebral hemorrhage (ICH). The aims of this study are to derive and validate a fully automated segmentation algorithm for ICH volumetric analysis using deep learning methods.

Methods—
In-patient computed tomography scans of 300 consecutive adults (age ≥18 years) with spontaneous, supratentorial ICH who were enrolled in the ICHOP (Intracerebral Hemorrhage Outcomes Project; 2009–2018) were separated into training (n=260) and test (n=40) datasets. A fully automated segmentation algorithm was derived using convolutional neural networks, and it was trained on manual segmentations from the training dataset. The algorithm’s performance was assessed against manual and semiautomated segmentation methods in the test dataset.

Results—

The mean volumetric Dice similarity coefficients for the fully automated segmentation algorithm when tested against manual and semiautomated segmentation methods were 0.894±0.264 and 0.905±0.254, respectively. ICH volumes derived from fully automated versus manual (
R
2
=0.981;
P
<0.0001), fully automated versus semiautomated (
R
2
=0.978;
P
<0.0001), and semiautomated versus manual (
R
2
=0.990;
P
<0001) segmentation methods had strong between-group correlations. The fully automated segmentation algorithm (mean 12.0±2.7 s/scan) was significantly faster than both of the manual (mean 201.5±92.2 s/scan;
P
<0.001) and semiautomated (mean 288.58±160.3 s/scan;
P
<0.001) segmentation methods.

Conclusions—
The fully automated segmentation algorithm quantified hematoma volumes from computed tomography scans of supratentorial ICH patients with similar accuracy and substantially greater efficiency compared with manual and semiautomated segmentation methods. External validation of the fully automated segmentation algorithm is warranted.
The Nerve to Thyrohyoid Muscle as a Novel Donor Nerve for Laryngeal Reinnervation
Authors: Graham M. Elise , Smith Marshall E. 
Published: November 2019

Objectives: Recurrent laryngeal nerve (RLN) injury may be a consequence of surgical procedures of the skull base, neck, and chest, with adverse consequences to function and quality of life. Laryngeal reinnervation offers a potentially stable improvement in vocal fold position and tone. The classic donor nerve is the ansa cervicalis, but is not always available due to damage or sacrifice during previous neck surgeries. Our objective was to introduce the nerve to the thyrohyoid (TH) muscle as an alternate donor nerve for reinnervation, which has not previously been described. Methods: Case series of two patients using the TH nerve for laryngeal reinnervation after RLN injury, with description of surgical harvest. Results: Follow-up results are available for 10 months (one patient) and 3 years (one patient) demonstrating both subjective and objective improvement in function. GRBAS scores were reduced. Maximal phonation time was improved. Patient rating of voice was stable or improved postoperatively. One patient described significant preoperative dyspnea which was significantly improved postoperatively, from a score of 24 to 10 out of 40 on the dyspnea handicap index. VHI was improved in one patient, but scores elevated in the other, despite a change from “moderately severe impairment” to “normal voice” subjectively. Neither patient experienced significant complications from the procedure. Conclusion: Laryngeal reinnervation procedures provide good outcomes in pediatric patients. When ansa cervicalis is not available as a donor nerve, the nerve to TH provides a reasonable alternative.
Multimodal Imaging of Nonenhancing Glioblastoma Regions
Authors: John Flóra , Robinette Natasha L. , Amit-Yousif Alit J. , Bosnyák Edit , Barger Geoffrey R. , Shah Keval D. , Mittal Sandeep , Juhász Csaba 
Published: November 2019

Background: Clinical glioblastoma treatment mostly focuses on the contrast-enhancing tumor mass. Amino acid positron emission tomography (PET) can detect additional, nonenhancing glioblastoma-infiltrated brain regions that are difficult to distinguish on conventional magnetic resonance imaging (MRI). We combined MRI with perfusion imaging and amino acid PET to evaluate such nonenhancing glioblastoma regions. Methods: Structural MRI, relative cerebral blood volume (rCBV) maps from perfusion MRI, and α-[11C]-methyl-l-tryptophan (AMT)-PET images were analyzed in 20 patients with glioblastoma. The AMT uptake and rCBV (expressed as tumor to normal [T/N] ratios) were compared in nonenhancing tumor portions showing increased signal on T2/fluid-attenuated inversion recovery (T2/FLAIR) images. Results: Thirteen (65%) tumors showed robust heterogeneity in nonenhancing T2/FLAIR hyperintense areas on AMT-PET, whereas the nonenhancing regions in the remaining 7 cases had homogeneous AMT uptake (low in 6, high in 1). AMT and rCBV T/N ratios showed only a moderate correlation in the nonenhancing regions ( r = 0.41, P = .017), but regions with very low rCBV (<0.79 T/N ratio) had invariably low AMT uptake. Conclusions: The findings demonstrate the metabolic and perfusion heterogeneity of nonenhancing T2/FLAIR hyperintense glioblastoma regions. Amino acid PET imaging of such regions can detect glioma-infiltrated brain for treatment targeting; however, very low rCBV values outside the contrast-enhancing tumor mass make increased AMT uptake in nonenhancing glioblastoma regions unlikely.
A Scoping Review on the Use of Antibiotic-Impregnated Beads and Applications to Vascular Surgery
Authors: McGuinness Brandon , Ali Khatija Pinky , Phillips Steven , Stacey Michael 
Published: November 2019

Introduction: Surgical site infection (SSI) presents a ubiquitous concern to surgical specialties, especially in the presence of prosthetic material. Antibiotic-impregnated beads present a novel and evolving means to combat this condition. This review aims to analyze the quality of evidence and methods of antibiotic bead use, particularly for application within vascular surgery. Methods: A systematic scoping review was conducted within Embase, MEDLINE, and the Cochrane Registry of Randomized Controlled Trials. Articles were evaluated by 2 independent reviewers. Level of evidence was evaluated using the Oxford Center for Evidence-Based Medicine Criteria and the Cochrane Risk of Bias Tool for Randomized Controlled Trials. Results: The search yielded 6951 papers, with 275 included for final analysis. Publications increased in frequency from 1978 to the present. The most common formulation was polymethyl methacrylate; however publications on biodegradable formulations, including calcium sulfate beads, have been published with increasing frequency. Most publications had positive conclusions (94.2%); however, the data was mainly subjective and may be prone to publication bias. Only 11 randomized controlled trials were identified and all but one was evaluated to be at a high risk of bias. The most common indication was for osteomyelitis (52%), orthopedic prosthetic infections (20%), and trauma (9%). Within vascular surgery, beads have been used primarily for the treatment of graft infection, with freedom from recurrence rates being reported from 41% to 87.5%. Conclusions: Antibiotic-impregnated beads provide a means to deliver high doses of antibiotic directly to a surgical site, without the risks of parenteral therapy. There has yet to be significant high-level quality data published on their use. There is a large body of evidence that suggests antibiotic beads may be used in SSIs in high-risk patients, prosthetic infections, and other complex surgical infections. Important potential areas of application in vascular surgery include graft infection, prevention of wound infection in high-risk patients, and diabetic foot infection.
Spinal Injury in Indian Children: Review of 204 Cases
Authors: Bansal M. L. , Sharawat Rajesh , Mahajan Rajat , Dawar Hitesh , Mohapatra Bibhudendu , Das Kalidutta , Chhabra Harvinder Singh 
Published: November 2019

Study design: Retrospective study. Objective: The purpose of the study was to analyze the epidemiological parameters and associated factors after spinal cord injury (SCI) in children, in the last 14 years admitted at a tertiary care center (Indian Spinal Injury Centre [ISIC], New Delhi, India). Method: The demographic and injury-related data was analyzed descriptively. The incidence, type, and level of injury were compared across the age groups using a χ2 test. Wherever appropriate, Fisher exact test was used. Results: There were 1660 pediatric trauma cases admitted at ISIC from 2002 to 2015, where 204 cases presented with spine injuries. The average age of children sustaining spine injury was 15.69 years (3-18 years of range). There were 15 patients in the age group 0 to 9 years, 27 patients in the age group 10 to 14 years, and 162 patients in the age group 15 to 18 years. This difference in spine injury incidence among the age groups was statistically significant. Fall from height was a common mode of injury. In our sample, boys were 3 times more likely to be injured than girls. Burst fractures were common among the type of injuries. Conclusion: Our study confirms the predominance of cervical spine injury and the high incidence of multilevel contiguous with a lesser percentage of noncontiguous multilevel spinal involvement. SCIWORA (spinal cord injury without radiological abnormality) incidences were in a similar context to the literature available. There was a very low incidence of death. Neurological improvement was seen in 8 operated cases and 4 conservatively treated cases.
Disruptive Innovation in Indian Aerospace and Defence Industry
Authors: Rao Shuktij Singh , Banik Arindam , Khanna Ashutosh , Philip Deepu 
Published: November 2019

This article analyses disruptive innovation in Indian aerospace and defence industry using a theoretical model developed on the basis of Christensen’s framework for analysing disruptive innovation and by addressing the requirements of aerospace and defence industry. This framework is then used to collect data from key stakeholders and analyse the movements of Indian aerospace and defence industry. Analysis of a large sample of data reveals that there are forces of disruptive innovation that have been set in motion in the Indian aerospace and defence industry by recent events driven by the signals of changes in the industry and the steps taken by Government of India; however, they do not appear to be sufficient to be able to drive innovation and business activity that may amount to a scale of disruptive innovation due to lack of user participation and inadequate access to the global network of technology and management expertise. JEL Classifications: O31, O32, O33, O38
Prevalence of the JAK2 V617F Mutation in Patients with Peripheral Arterial Disease
Authors: Kinz Elena , Gasser Klaus , Muendlein Axel , Leiherer Andreas , Steurer Michael , Fraunberger Peter , Lang Alois , Drexel Heinz 
Published: November 2019

Abstract
Introduction:
The acquired JAK2 V617F mutation is common in patients with myeloproliferative neoplasms and increases thrombotic risk. We previously showed that JAK2 V617F is also found in healthy subjects as well as in patients with coronary artery disease (0.6% and 1.3%, respectively). Peripheral arterial disease (PAD) is an important manifestation of diffuse atherosclerosis and PAD patients are at exceptionally high risk for cardiovascular events, showing a worse prognosis than that of patients with coronary artery disease Due to the close relation of the JAK2 V617F mutation to thrombotic events we hypothesized that this mutation may play an important role in the risk management of PAD patients. However, prevalence of JAK2 V617F or of occult myeloproliferative neoplasms is unknown in PAD patients.
Methods:
In the present study we determined the prevalence of JAK2 V617F in a cohort of 287 patients with sonographically proven PAD. JAK2 mutational status from 997 age-matched healthy people was available from a previous study. JAK2 V617F screening and quantification of allele burden in both cohorts was performed with allele-specific quantitative real-time PCR.
Results:
From a total of 287 PAD patients samples, 9 (3.1%) were tested positive for JAK2 V617F mutation corresponding to a 5-fold, highly significant increase compared with healthy people (p<0.001). Mutant allele burden of JAK2 V617F positive samples was ranging between 0.2% and 96.2% (median=0.75%). Generally, our study showed no significant association of the JAK2 V617F mutation with abnormal blood cell counts. However, the patient with the highest mutant allele burden showed elevated hemoglobin values (> 18.5 g/dL) indicating polycythemia vera (PV).
Conclusion:
We conclude that the prevalence of JAK2 V617F mutation is significantly increased in PAD patients compared to the general population. For this reason mutation analysis should be considered in PAD patients with abnormal blood cell counts to identify occult myeloproliferative neoplasms and to adjust therapeutic treatment, possibly reducing the risk of future vascular complications.

Disclosures
No relevant conflicts of interest to declare.
Psychological burden in family caregivers of patients with advanced cancer at initiation of specialist inpatient palliative care
Authors: Oechsle Karin , Ullrich Anneke , Marx Gabriella , Benze Gesine , Heine Julia , Dickel Lisa-Marie , Zhang Youyou , Wowretzko Feline , Wendt Kim Nikola , Nauck Friedemann , Bokemeyer Carsten , Bergelt Corinna 
Published: November 2019

Abstract
Background
This study prospectively evaluated distress, depressive and anxiety symptoms as well as associated factors in family caregivers (FC) of advanced cancer patients at initiation of specialist inpatient palliative care.

Methods
Within 72 h after the patient’s first admission, FCs were asked to complete German versions of the Distress Thermometer, Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire depression module 9-item scale (PHQ-9) for outcome measure. Multivariate logistic regression analyses were used to identify associated factors.

Results
In 232 FCs (62% spouses/partners), mean level of distress was 7.9 (SD 1.8; range, 2–10) with 95% presenting clinically relevant distress levels. Most frequent problems were sadness (91%), sorrows (90%), anxiety (78%), exhaustion (77%) and sleep disturbances (73%). Prevalence rates of moderate to severe anxiety and depressive symptoms were 47 and 39%, respectively. Only 25% of FCs had used at least one source of support previously. In multivariate regression analysis, being female (OR 2.525), spouse/partner (OR 2.714), exhaustion (OR 10.267), and worse palliative care outcome ratings (OR 1.084) increased the likelihood for moderate to severe anxiety symptom levels. Being female (OR 3.302), low socio-economic status (OR 6.772), prior patient care other than home-based care (OR 0.399), exhaustion (OR 3.068), sleep disturbances (OR 4.183), and worse palliative care outcome ratings (OR 1.100) were associated with moderate to severe depressive symptom levels.

Conclusions
FCs of patients presenting with indication for specialist palliative care suffer from high distress and relevant depressive and anxiety symptoms, indicating the high need of psychological support not only for patients, but also their FCs. Several socio-demographic and care-related risk-factors influence mental burden of FCs and should be in professional caregivers’ focus in daily clinical practice.
Concurrent genome and epigenome editing by CRISPR-mediated sequence replacement
Authors: Alexander Jes , Findlay Gregory M. , Kircher Martin , Shendure Jay 
Published: November 2019

Abstract
Background
Recent advances in genome editing have facilitated the direct manipulation of not only the genome, but also the epigenome. Genome editing is typically performed by introducing a single CRISPR/Cas9-mediated double-strand break (DSB), followed by non-homologous end joining (NHEJ)- or homology-directed repair-mediated repair. Epigenome editing, and in particular methylation of CpG dinucleotides, can be performed using catalytically inactive Cas9 (dCas9) fused to a methyltransferase domain. However, for investigations of the role of methylation in gene silencing, studies based on dCas9-methyltransferase have limited resolution and are potentially confounded by the effects of binding of the fusion protein. As an alternative strategy for epigenome editing, we tested CRISPR/Cas9 dual cutting of the genome in the presence of in vitro methylated exogenous DNA, with the aim of driving replacement of the DNA sequence intervening the dual cuts via NHEJ.

Results
In a proof of concept at the HPRT1 promoter, successful replacement events with heavily methylated alleles of a CpG island resulted in functional silencing of the HPRT1 gene. Although still limited in efficiency, our study demonstrates concurrent epigenome and genome editing in a single event.

Conclusions
This study opens the door to investigations of the functional consequences of methylation patterns at single CpG dinucleotide resolution. Our results furthermore support the conclusion that promoter methylation is sufficient to functionally silence gene expression.
Parent–child cooking meal together may relate to parental concerns about the diets of their toddlers and preschoolers: a cross-sectional analysis in Japan
Authors: Ishikawa Midori , Eto Kumi , Miyoshi Miki , Yokoyama Tetsuji , Haraikawa Mayu , Yoshiike Nobuo 
Published: November 2019

Abstract
Background
Parents often have concerns about the food habits of their young children. Cooking is a frequent behavior related to dietary activities at home. We hypothesized that “a parent cooking meals together with young children might alleviate dietary concerns.” The aim of this study was to identify the relationship between parental cooking practices (e.g., cooking meals together with the child) and diet-related concerns.

Methods
Data were extracted from the “National nutrition survey on preschool children” conducted among nation-wide households with toddlers and preschoolers in 2015 by the Ministry of Health, Labour and Welfare of Japan. Parents were classified into two groups comprising those who cooked meals together with their children and those who did not. The following variables were compared: taking too much time to eat (slow eaters), “picky” eating (eating only certain foods), inconsistent food intake (eating too much or too little), playing with food/utensils while eating, preferring sweetened beverages and snacks over meals, eating too fast to chew well, not swallowing food, disinterested in eating, and spitting out food. The associations between parent–child cooking meals together and the concerns pertaining to the child’s dietary habits and food intake were analyzed and compared between the two groups.

Results
The concerns of “picky eating” and “playing with food/utensils while eating” were lower, while “eating too much” was higher in the parent-cooking together group. The intake frequency of fish, soybeans/soy products, vegetables, and milk among children were higher in the “cooking together” group than among those in the “not cooking together” group. Children in the “cooking together” group consumed a significantly greater variety of foods than those in the “not cooking together” group.

Conclusions
Cooking a meal together with a child may be related to the parent’s lower concerns about the dietary habits of the child, including “picky eating” and “playing with food/utensils while eating,” but may also be related to the higher concerns of “eating too much.”