bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multi-institution evaluation of clinical profile anonymization
Authors: Heatherly Raymond , Rasmussen Luke V , Peissig Peggy L , Pacheco Jennifer A , Harris Paul , Denny Joshua C , Malin Bradley A 
Published: November 2015

Abstract
Background and objective: There is an increasing desire to share de-identified electronic health records (EHRs) for secondary uses, but there are concerns that clinical terms can be exploited to compromise patient identities. Anonymization algorithms mitigate such threats while enabling novel discoveries, but their evaluation has been limited to single institutions. Here, we study how an existing clinical profile anonymization fares at multiple medical centers.
Methods: We apply a state-of-the-art k -anonymization algorithm, with k set to the standard value 5, to the International Classification of Disease, ninth edition codes for patients in a hypothyroidism association study at three medical centers: Marshfield Clinic, Northwestern University, and Vanderbilt University. We assess utility when anonymizing at three population levels: all patients in 1) the EHR system; 2) the biorepository; and 3) a hypothyroidism study. We evaluate utility using 1) changes to the number included in the dataset, 2) number of codes included, and 3) regions generalization and suppression were required.
Results: Our findings yield several notable results. First, we show that anonymizing in the context of the entire EHR yields a significantly greater quantity of data by reducing the amount of generalized regions from ∼15% to ∼0.5%. Second, ∼70% of codes that needed generalization only generalized two or three codes in the largest anonymization.
Conclusions: Sharing large volumes of clinical data in support of phenome-wide association studies is possible while safeguarding privacy to the underlying individuals.
Classification of radiology reports for falls in an HIV study cohort
Authors: Bates Jonathan , Fodeh Samah J , Brandt Cynthia A , Womack Julie A 
Published: November 2015

AbstractObjective To identify patients in a human immunodeficiency virus (HIV) study cohort who have fallen by applying supervised machine learning methods to radiology reports of the cohort.Methods We used the Veterans Aging Cohort Study Virtual Cohort (VACS-VC), an electronic health record-based cohort of 146 530 veterans for whom radiology reports were available ( N =2 977 739). We created a reference standard of radiology reports, represented each report by a feature set of words and Unified Medical Language System concepts, and then developed several support vector machine (SVM) classifiers for falls. We compared mutual information (MI) ranking and embedded feature selection approaches. The SVM classifier with MI feature selection was chosen to classify all radiology reports in VACS-VC.Results Our SVM classifier with MI feature selection achieved an area under the curve score of 97.04 on the test set. When applied to all the radiology reports in VACS-VC, 80 416 of these reports were classified as positive for a fall. Of these, 11 484 were associated with a fall-related external cause of injury code (E-code) and 68 932 were not, corresponding to 29 280 patients with potential fall-related injuries who could not have been found using E-codes.Discussion Feature selection was crucial to improving the classifier’s performance. Feature selection with MI allowed us to select the number of discriminative features to use for classification, in contrast to the embedded feature selection method, in which the number of features is chosen automatically.Conclusion Machine learning is an effective method of identifying patients who have suffered a fall. The development of this classifier supplements the clinical researcher’s toolkit and reduces dependence on under-coded structured electronic health record data.
Regulatory Solutions to the Problem of High Generic Drug Costs
Authors: Luo Jing , Sarpatwari Ameet , Kesselheim Aaron S. 
Published: November 2015

Abstract
Recent reports have highlighted dramatic price increases for several older generic drugs, including a number of essential products used to treat deadly infectious diseases. Although most of these medicines have been widely available at reasonable prices for decades, some manufacturers have seized on unique features of the pharmaceutical marketplace to seek substantial profits. In this Perspective, we examine limitations in current price regulation among public and private payors and consider several reforms that could address the problem of expensive generic drugs through improved competition.
Inflammation Increases Neuronal Sensitivity to General Anesthetics
Authors: Avramescu Sinziana , Wang Dian-Shi , Lecker Irene , To William T. H. , Penna Antonello , Whissell Paul D. , Mesbah-Oskui Lia , Horner Richard L. , Orser Beverley A. 
Published: November 2015

AbstractAbstract
The inflammatory cytokine interleukin-1β increased γ-aminobutyric acidergic inhibitory currents in the presence of etomidate or isoflurane in cultured mouse hippocampal and cortical neurons. In a mouse model of sepsis, behavioral sensitivity to both anesthetics was increased. The clinical relevance of these findings will require studies of specific anesthetic endpoints in patients with systemic inflammation.

Background
Critically ill patients with severe inflammation often exhibit heightened sensitivity to general anesthetics; however, the underlying mechanisms remain poorly understood. Inflammation increases the number of γ-aminobutyric acid type A (GABAA) receptors expressed on the surface of neurons, which supports the hypothesis that inflammation increases up-regulation of GABAA receptor activity by anesthetics, thereby enhancing the behavioral sensitivity to these drugs.

Methods
To mimic inflammation in vitro, cultured hippocampal and cortical neurons were pretreated with interleukin (IL)-1β. Whole cell patch clamp methods were used to record currents evoked by γ-aminobutyric acid (GABA) (0.5 μM) in the absence and presence of etomidate or isoflurane. To mimic inflammation in vivo, mice were treated with lipopolysaccharide, and several anesthetic-related behavioral endpoints were examined.

Results
IL-1β increased the amplitude of current evoked by GABA in combination with clinically relevant concentrations of either etomidate (3 μM) or isoflurane (250 μM) (n = 5 to 17, P < 0.05). Concentration–response plots for etomidate and isoflurane showed that IL-1β increased the maximal current 3.3-fold (n = 5 to 9) and 1.5-fold (n = 8 to 11), respectively (P < 0.05 for both), whereas the half-maximal effective concentrations were unchanged. Lipopolysaccharide enhanced the hypnotic properties of both etomidate and isoflurane. The immobilizing properties of etomidate, but not isoflurane, were also increased by lipopolysaccharide. Both lipopolysaccharide and etomidate impaired contextual fear memory.

Conclusions
These results provide proof-of-concept evidence that inflammation increases the sensitivity of neurons to general anesthetics. This increase in anesthetic up-regulation of GABAA receptor activity in vitro correlates with enhanced sensitivity for GABAA receptor–dependent behavioral endpoints in vivo.
The Classification for Early-onset Scoliosis (C-EOS) Correlates With the Speed of Vertical Expandable Prosthetic Titanium Rib (VEPTR) Proximal Anchor Failure
Authors: Park Howard Y. , Matsumoto Hiroko , Feinberg Nicholas , Roye David P. , Kanj Wajdi W. , Betz Randal R. , Cahill Patrick J. , Glotzbecker Michael P. , Luhmann Scott J. , Garg Sumeet , Sawyer Jeffrey R. , Smith John T. , Flynn John M. , Vitale Michael G. 
Published: November 2015

Background:
The Classification for Early-onset Scoliosis (C-EOS) was developed by a consortium of early-onset scoliosis (EOS) surgeons. This study aims to examine if the C-EOS classification correlates with the speed (failure/unit time) of proximal anchor failure in EOS surgery patients.

Methods:
A total of 106 EOS patients were retrospectively queried from an EOS database. All patients were treated with vertical expandable prosthetic titanium rib and experienced proximal anchor failure. Patients were classified by the C-EOS, which includes a term for etiology [C: Congenital (54.2%), M: Neuromuscular (32.3%), S: Syndromic (8.3%), I: Idiopathic (5.2%)], major curve angle [1: ≤20 degrees (0%), 2: 21 to 50 degrees (15.6%), 3: 51 to 90 degrees (66.7%), 4: >90 degrees (17.7%)], and kyphosis [“−”: ≤20 (13.5%), “N”: 21 to 50 (42.7%), “+”: >50 (43.8%)]. Outcome was measured by time and number of lengthenings to failure.

Results:
Analyzing C-EOS classes with >3 subjects, survival analysis demonstrates that the C-EOS discriminates low, medium, and high speed of failure. The low speed of failure group consisted of congenital/51-90/hypokyphosis (C3−) class. The medium-speed group consisted of congenital/51-90/normal and hyperkyphosis (C3N, C3+), and neuromuscular/51-90/hyperkyphosis (M3+) classes. The high-speed group consisted of neuromuscular/51-90/normal kyphosis (M3N), and neuromuscular/>90/normal and hyperkyphosis (M4N, M4+) classes. Significant differences were found in time (P<0.05) and number of expansions (P<0.05) before failure between congenital and neuromuscular classes.
As isolated variables, neuromuscular etiology experienced a significantly faster time to failure compared with patients with idiopathic (P<0.001) and congenital (P=0.026) etiology. Patients with a major curve angle >90 degrees demonstrated significantly faster speed of failure compared with patients with major curve angle 21 to 50 degrees (P=0.011).

Conclusions:
The ability of the C-EOS to discriminate the speeds of failure of the various classification subgroups supports its validity and demonstrates its potential use in guiding decision making. Further experience with the C-EOS may allow more tailored treatment, and perhaps better outcomes of patients with EOS.

Level of Evidence:
Level III.
The Fate of Iliopsoas Muscle in the Long-term Follow-up After Open Reduction of Developmental Dysplasia of the Hip by Medial Approach. Part 1: MRI Evaluation
Authors: Yilmaz Serdar , Aksahin Ertugrul , Duran Semra , Bicimoglu Ali 
Published: November 2015

Background:
There has been little information about the long-term status of the iliopsoas, which is the main flexor of the hip, after iliopsoas tenotomy in the treatment of developmental dysplasia of the hip (DDH). The aim of this study was to assess the status of the iliopsoas muscle and other flexors and extensors of the hip in long-term follow-up with magnetic resonance imaging after complete iliopsoas tenotomy in patients with unilateral DDH treated with open reduction with a medial approach.

Methods:
The study included 20 patients who underwent open reduction with a medial approach for unilateral DDH and had long-term follow-up. Magnetic resonance imaging assessment of iliopsoas, rectus femoris, tensor fasia lata, sartorius, and gluteus maximus muscles was applied and the muscles of the hip that was operated on were compared with the unoperated hip. In addition, the iliopsoas muscle was examined for reattachment and the effect of reattachment was evaluated.

Results:
The mean age at the time of operation was 10.53±3.61 months (range, 5 to 18 mo), and mean follow-up was 16.65±2.16 years (range, 13 to 20 y). Spontaneous reattachment of the iliopsoas was observed in 18 patients (90%), either in the lesser trochanter (65%) or the superior part of it (25%). There was no significant difference between the hips that were operated on and those that were not with regard to the mean cross-sectional areas (CSA) of the tensor fascia lata, rectus femoris, sartorius, and gluteus maximus muscles. The CSA of the tensor fascia lata, rectus femoris, sartorius, and gluteus maximus muscles showed no significant difference (P>0.05); however, CSA of iliopsoas muscle was significantly reduced in the operated hip (P<0.001).

Conclusions:
Although the iliopsoas tendon was atrophied after complete iliopsoas tenotomy, it was reattached in 90% of the patients spontaneously in long-term follow-up. There was no statistically significant compensatory hypertrophy in any muscles in response to iliopsoas atrophy.

Level of Evidence:
Level IV—Therapeutic.
Natural Disasters
Authors: Wynn Stephanie T. 
Published: November 2015

ABSTRACT:
Natural disasters leave survivors suffering physically, psychologically, and spiritually. An EF4 tornado on April 27, 2011, in Tuscaloosa, Alabama, known as April's Fury, raised the question of how mental health practitioners (MHPs) might respond to address psychological needs, rather than being exclusively assigned to offer physical support immediately following a disaster. This article proposes planning ahead for MHPs to provide psychological first aid (PFA) in the immediate aftermath of a catastrophe. Combating psychological issues early will hopefully help reduce the development of posttraumatic stress disorder (PTSD) or prolonged grief disorder (PGD) in survivors.
Lowering Uric Acid with Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia
Authors: Takir Mumtaz , Kostek Osman , Ozkok Abdullah , Elcioglu Omer Celal , Bakan Ali , Erek Aybala , Mutlu Hasan Huseyin , Telci Ozge , Semerci Aysun , Odabas Ali Riza , Afsar Baris , Smits Gerard , Alanaspa Miguel , Sharma Shailendra , Johnson Richard J. , Kanbay Mehmet 
Published: November 2015

Background Hyperuricemia is an independent predictor of impaired fasting glucose and type 2 diabetes, but whether it has a causal role in insulin resistance remains controversial. Here we tested the hypothesis that lowering uric acid in hyperuricemic nondiabetic subjects might improve insulin resistance. Methods Subjects with asymptomatic hyperuricemia (n = 73) were prospectively placed on allopurinol (n = 40) or control (n = 33) for 3 months. An additional control group consisted of 48 normouricemic subjects. Serum uric acid, fasting glucose, fasting insulin, HOMA-IR (homeostatic model assessment of insulin resistance), and high-sensitivity C-reactive protein were measured at baseline and at 3 months. Results Allopurinol-treated subjects showed a reduction in serum uric acid in association with improvement in fasting blood glucose, fasting insulin, and HOMA-IR index, as well as a reduction in serum high-sensitivity C-reactive protein. The number of subjects with impaired fasting glucose significantly decreased in the allopurinol group at 3 months compared with baseline (n = 8 [20%] vs n = 30 [75%], 3 months vs baseline, P < 0.001). In the hyperuricemic control group, only glucose decreased significantly and, in the normouricemic control, no end point changed. Conclusions Allopurinol lowers uric acid and improves insulin resistance and systemic inflammation in asymptomatic hyperuricemia. Larger clinical trials are recommended to determine if lowering uric acid can help prevent type 2 diabetes.
Laughing Gas in a Pediatric Emergency Department—Fun for All Participants
Authors: Staubli Georg , Baumgartner Matthias , Sass Jörn Oliver , Hersberger Martin 
Published: November 2015

The efficiency of nitrous oxide in an equimolar mixture with oxygen or in concentrations up to 70% is approved for short painful procedures. Evaluation of the vitamin B12 levels in anesthetic staff applying nitrous oxide showed reduced vitamin B12 plasma levels. This study examines the vitamin B12 status of medical staff working with nitrous oxide in a pediatric emergency department (ED). Medical staff of the ED at the University Children's Hospital Zurich participated. The vitamin B12 status was evaluated by measuring homocysteine, methylmalonic acid, vitamin B12, blood count, and the MTHFR C677T genotype. As a control group, medical personnel working in the “nitrous oxide–free” pediatric intensive care unit were recruited.

Results
The parameters for the vitamin B12 status of all participants were in the reference range, and there were no significant differences for the 2 groups. By trend, the ED staff showed higher vitamin B12 levels. The ED staff members were slightly older (P = 0.07) and had higher hemoglobin levels (P < 0.04) compared with the pediatric intensive care unit staff.

Conclusions
The use of nitrous oxide (50%-70%) with a demand valve is safe for the vitamin B12 status of medical personnel in the ED.
Is Level of Serum Ischemia-Modified Albumin A Useful Biomarker in Carbon Monoxide Poisoning Cases?
Authors: Kocaoglu Celebi , Erdem Said Sami , Ozel Ahmet 
Published: November 2015

Objectives
Ischemia-modified albumin (IMA) is an emerging diagnostic biomarker for many ischemic conditions. The study was conducted to investigate whether there is a change in IMA levels in carbon monoxide poisoning and, if so, the clinical relevance of IMA levels.

Methods
This study was performed between October 2013 and April 2014 to compare levels of serum IMA drawn at the time of admission to the emergency department in 49 patients poisoned with carbon monoxide and 37 healthy controls. Serum IMA, blood carboxyhemoglobin, and lactate levels were analyzed.

Results
Ischemia-modified albumin levels of patients with carbon monoxide poisoning were higher than those of controls. In patient group, however, there was no correlation between serum IMA and carboxyhemoglobin levels (r = −0.244, P > 0.05), whereas a negative correlation was detected between serum IMA and lactate levels (r = −0.334, P < 0.05). After all, a positive correlation was present between carboxyhemoglobin and lactate levels (r = 0.399, P < 0.05).

Conclusions
Results from this preliminary study suggest that IMA might have diagnostic value in carbon monoxide poisoning and may be a parameter to be used clinically together with carboxyhemoglobin levels in terms of reflecting tissue hypoxia. In addition, IMA may be a criterion, especially in delayed cases where carboxyhemoglobin level may be normal in deciding hyperbaric oxygen treatment. To clarify this issue, further studies with larger population are needed.
Rapid Genotype Refinement for Whole-Genome Sequencing Data using Multi-Variate Normal Distributions
Authors: Arthur Rudy , O’Connell Jared , Schulz-Trieglaff Ole , Cox Anthony J. 
Published: November 2015

ABSTRACTWhole-genome low-coverage sequencing has been combined with linkage-disequilibrium (LD) based genotype refinement to accurately and cost-effectively infer genotypes in large cohorts of individuals. Most genotype refinement methods are based on hidden Markov models, which are accurate but computationally expensive. We introduce an algorithm that models LD using a simple multivariate Gaussian distribution. The key feature of our algorithm is its speed, it is hundreds of times faster than other methods on the same data set and its scaling behaviour is linear in the number of samples. We demonstrate the performance of the method on both low-coverage and high-coverage samples.Availability: The source code is available athttps://github.com/sequencing/marvinContact:rarthur@illumina.com
Unraveling the mechanism of proton translocation in the extracellular half-channel of bacteriorhodopsin
Authors: Ge Xiaoxia , Gunner M. R. 
Published: November 2015

AbstractBacteriorhodopsin, a light activated protein that creates a proton gradient in halobacteria, has long served as a simple model of proton pumps. Within bacteriorhodopsin, several key sites undergo protonation changes during the photocycle, moving protons from the higher pH cytoplasm to the lower pH extracellular side. The mechanism underlying the long-range proton translocation between the central (the retinal Schiff base SB216, D85 and D212) and exit clusters (E194 and E204) remains elusive. To obtain a dynamic view of the key factors controlling proton translocation, a systematic study using molecular dynamics simulation was performed for eight bacteriorhodopsin models varying in retinal isomer and protonation of the SB216, D85, D212 and E204. The side-chain orientation of R82 is determined primarily by the protonation states of the residues in the EC. The side-chain reorientation of R82 modulates the hydrogen-bond network and consequently possible pathways of proton transfer. Quantum mechanical intrinsic reaction coordinate calculations of proton-transfer in the methyl guanidinium-hydronium-hydroxide model system show that proton transfer via a guanidinium group requires an initial geometry permitting proton donation and acceptance by the same amine. In all the models, R82 can form proton wires with both the CC and the EC connected by the same amine. Alternatively, rare proton wires for proton transfer from the CC to the EC without involving R82 were found in an O’ state where the proton on D85 is transferred to D212.
A spectral analysis approach to detect actively translated open reading frames in high-resolution ribosome profiling data
Authors: Calviello Lorenzo , Mukherjee Neelanjan , Wyler Emanuel , Zauber Henrik , Hirsekorn Antje , Selbach Matthias , Landthaler Markus , Obermayer Benedikt , Ohler Uwe 
Published: November 2015

AbstractRNA sequencing protocols allow for quantifying gene expression regulation at each individual step, from transcription to protein synthesis. Ribosome Profiling (Ribo-seq) maps the positions of translating ribosomes over the entire transcriptome. Despite its great potential, a rigorous statistical approach to identify translated regions by means of the characteristic three-nucleotide periodicity of Ribo-seq data is not yet available. To fill this gap, we developed RiboTaper, which quantifies the significance of periodic Ribo-seq reads via spectral analysis methods.We applied RiboTaper on newly generated, deep Ribo-seq data in HEK293 cells, to derive an extensive map of translation that covers Open Reading Frame (ORF) annotations for more than 11,000 protein-coding genes. We also find distinct ribosomal signatures for several hundred detected upstream ORFs and ORFs in annotated non-coding genes (ncORFs). Mass spectrometry data confirms that RiboTaper achieves excellent coverage of the cellular proteome and validates dozens of novel peptide products. Collectively, RiboTaper (available athttps://ohlerlab.mdc-berlin.de/software/) is a powerful method for comprehensivede novoidentification of actively used ORFs in the human genome.