bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomechanical Stability of Primary and Revision Sacroiliac Joint Fusion Devices: A Cadaveric Study
Authors: Carbone Jake , Swink Isaac , Muzzonigro Thomas , Diehl Daniel , Oh Michael , Lindsey Derek P. , Yerby Scott , Cheng Boyle C. 
Published: September 2020

Study Design: An in vitro biomechanics study. Objective: To evaluate the efficacy of triangular titanium implants in providing mechanical stabilization to a sacroiliac joint with primary and revision sized implants. Methods: Ten lumbopelvic cadaveric specimens were tested in 4 stages: intact, pubic symphysis sectioned, primary, and simulated revision. Primary treatment was performed using 3 laterally placed triangular titanium implants. To simulate revision conditions before and after bone ingrowth and ongrowth on the implants, 7.5-mm and 10.75-mm implants were randomly assigned to one side of each specimen during the simulated revision stage. A 6 degrees of freedom spinal loading frame was used to load specimens in 4 directions: flexion extension, lateral bending, axial torsion, and axial compression. Biomechanical evaluation was based on measures of sacroiliac joint rotational and translational motion. Results: Both primary and revision implants showed the ability to reduce translational motion to a level significantly lower than the intact condition when loaded in axial compression. Simulated revision conditions showed no statistically significant differences compared with the primary implant condition, with the exception of flexion-extension range of motion where motions associated with the revised condition were significantly lower. Comparison of rotational and translation motions associated with the 7.5- and 10.75-mm implants showed no significant differences between the treatment conditions. Conclusions: These results indicate that implantation of laterally placed triangular titanium implants significantly reduces the motion of a sacroiliac joint using either the primary and revision sized implants. No statistically significant differences were detected when comparing the efficacy of primary, 7.5-mm revision, or 10.75-mm revision implants.
Effects of Caffeine on Intervertebral Disc Cell Viability in a Whole Organ Culture Model
Authors: Raines Benjamin T. , Stannard James T. , Stricklin Olivia E. , Stoker Aaron M. , Choma Theodore J. , Cook James L. 
Published: September 2020

Study Design: Controlled laboratory study. Objective: To investigate the impact of exposure to physiologically relevant caffeine concentrations on intervertebral disc (IVD) cell viability and extracellular matrix composition (ECM) in a whole organ culture model as potential contributing mechanisms in development and progression of IVD disorders in humans. Primary outcome measures were IVD viable cell density (VCD) and ECM composition. Methods: A total of 190 IVD whole organ explants from tails of 16 skeletally mature rats—consisting of cranial body half, endplate, IVD, endplate, and caudal body half—were harvested. IVD explants were randomly assigned to 1 of 2 groups: uninjured (n = 90) or injured (20G needle disc puncture/aspiration method, n = 100). Explants from each group were randomly assigned to 1 of 3 treatment groups: low caffeine (LCAF: 5 mg/L), moderate caffeine (MCAF: 10 mg/L), and high caffeine (HCAF: 15 mg/L) concentrations. Results: Cell viability was significantly higher in the low-caffeine group compared with the high-caffeine group at day 7 ( P = .037) and in the low-caffeine group compared with the medium- and high-caffeine groups at day 21 ( P ≤ .004). Analysis of ECM showed that all uninjured and control groups had significantly higher ( P < .05) glycosaminoglycan concentrations compared with all injured groups. Furthermore, we observed a temporal, downward trend in proteoglycan to collagen ratio for the caffeine groups. Conclusions: Caffeine intake may be a risk factor for IVD degeneration, especially in conjunction with disc injury. Mechanisms for caffeine associated disc degeneration may involve cell and ECM, and further studies should elucidate mechanistic pathways and potential benefits for caffeine restriction.
Does the Size or Location of Lumbar Disc Herniation Predict the Need for Operative Treatment?
Authors: Divi Srikanth N. , Makanji Heeren S. , Kepler Christopher K. , Anderson D. Greg , Goyal Dhruv K. C. , Warner Eric D. , Galetta Matthew S. , Hilibrand Alan S. , Kaye I. David , Kurd Mark F. , Radcliff Kristen E. , Rihn Jeffrey A. , Woods Barrett I. , Vaccaro Alexander R. , Schroeder Gregory D. 
Published: September 2020

Study Design: Retrospective cohort study. Objective: The goal of this study was to determine whether the absolute size (mm2), relative size (% canal compromise), or location of a single-level, lumbar disc herniation (LDH) on axial and sagittal cuts of magnetic resonance imaging (MRI) were predictive of eventual surgical intervention. Methods: MRIs of 89 patients were reviewed, and patients were split into groups based on type of management received (34 nonoperative vs 55 microdiscectomy). Radiographic characteristics—including size of disc herniation (mm2), size of spinal canal (mm2), location of herniation on axial (central, paracentral, foraminal) and sagittal (disc level, suprapedicle, pedicle, infrapedicle) planes, and type of herniation (bulge, protrusion, extrusion, sequestration)—were measured by 2 independent, orthopedic spine fellows and compared between groups via univariate and multivariate analyses. Results: The operative group showed a significantly higher percentage of canal compromise (39.5% vs 31.1%, P = .001) compared to the nonoperative group. Multiple logistic regression analysis showed higher odds of eventual operative intervention for a disc protrusion (odds ratio [OR] 6.30 [1.99, 19.86], P = .002) or disc extrusion (OR 11.5 [1.63, 81.2], P = .014) for Rater 1 and a higher odds of eventual surgical management for a paracentral location for both Rater 1 and Rater 2 (OR = 3.39 [1.25, 9.22], P = .017, and OR = 5.46 [1.77, 16.8], P = .003, respectively). Conclusions: Disc herniations in a paracentral location were more likely to undergo operative treatment than those more centrally located, on axial MRI views.
Physical Examination Is Predictive of Cauda Equina Syndrome: MRI to Rule Out Diagnosis Is Unnecessary
Authors: Zusman Natalie L. , Radoslovich Stephanie S. , Smith Spencer J. , Tanski Mary , Gundle Kenneth R. , Yoo Jung Uck 
Published: September 2020

Study Design: Cross-sectional cohort study. Objectives: Cauda equina syndrome (CES) is a neurologic emergency, and delay in diagnosis can result in irreversible impairment. Our purpose was to determine the value of physical examination in diagnosis of CES in patients complaining of bladder and/or bowel complications in the emergency department. Methods: Adult patients at one tertiary academic medical center that endorsed bowel/bladder dysfunction, underwent a lumbar magnetic resonance imaging (MRI), and received an orthopedic spine surgery consultation from 2008 to 2017 were included. Patients consulted for trauma or tumor were excluded. A chart and imaging review was performed to collect demographic, physical examination, and treatment data. Sensitivity, specificity, and negative and positive predictive values were calculated, and fast-and-frugal decision trees (FFTs) were generated using R. Results: Of 142 eligible patients, 10 were diagnosed with CES. The sensitivity and specificity of the exam findings were highest for bulbocavernosus reflex (BCR) (100% and 100%), followed by rectal tone (80% and 86%), postvoid residual bladder (80% and 59%), and perianal sensation (60% and 68%). The positive predictive value was high for BCR (100%), but low for other findings (13% to 31%). However, negative predictive values were consistently high for all examinations (96% to 100%). Two FFTs utilizing combinations of voluntary rectal tone, perianal sensation, and BCR resulted in no false negatives. Conclusions: A combination of physical examination findings of lower sacral function is an effective means of ruling out CES and, with further study, may eliminate the need for MRI in many patients reporting back pain and bowel or bladder dysfunction.
Assessing Decision Support Needs of those in Mental Health Crisis Utilizing Cognitive Task Analysis
Authors: Johnson Amanda J. , Bisantz Ann M. , Reynolds Amy L. , Meier Scott T. 
Published: September 2020

Extended Abstract Previous research has shown that mental health diagnoses can impact cognitive functioning and decision-making abilities (Bosaipo et al 2017; Stergiopoulos et al 2015; Bora and Pantelis 2015; Rock et al 2014). Decision making difficulties can be particularly problematic when individuals in mental health crises are faced with decisions about their safety and wellbeing. Despite research establishing cognitive and decision-making difficulties for this population, there is an absence in the literature concerning decision support needs of those individuals. Human factors professionals possess a unique set of methods and skills to address these needs and support individuals to make healthier, safer decisions using the latest technologies. This research was part of a larger project aimed at design of a decision support based mobile application that would support individuals during mental health crises. Other phases of the research will include additional user requirements gathering, iterative prototyping, heuristic evaluation, and user testing.
Measuring Information Management at MCI Simulation: Instruments Evaluation and Comparison
Authors: Perry Omer , Jaffe Eli , Bitan Yuval 
Published: September 2020

Introduction: Information management (also known as “communication” or “gathering and analyzing information”) is one of the core tasks of MCI (Mass-Casualty Incident) commanders during the chaotic prehospital phase.1 To train EMS (emergency medical service) personnel on how to manage an MCI efficiently, simulation drills are conducted in which participant performance is evaluated. As such, varied instruments have been developed to measure information management quality during MCI simulations. Since every instrument could lead to different results, our goal at the current study was to evaluate what are the advantages of applying each one of the instruments. Methods: Three instruments were chosen for the current study: (1) The Self-Assessment Teamwork Tool for Students (SATTS), (2) a set of performance indicators aimed to be scored by an experienced observer, and (3) Dynamic Information Management Quantification Instrument (DIMQI) which allows quantifying information items. All instruments were applied to the same MCI simulation. Results and Conclusions: Applying each of the instruments yielded a different layer of information. Thus, researchers and instructors consider using all three instruments as they are complementary to each other.
γ-Glutamyl carboxylase mutations differentially affect the biological function of vitamin K–dependent proteins
Authors: Hao Zhenyu , Jin Da-Yun , Chen Xuejie , Schurgers Leon J. , Stafford Darrel W. , Tie Jian-Ke 
Published: September 2020

Abstract
γ-Glutamyl carboxylase (GGCX) is an integral membrane protein that catalyzes posttranslational carboxylation of a number of vitamin K–dependent (VKD) proteins involved in a wide variety of physiologic processes, including blood coagulation, vascular calcification, and bone metabolism. Naturally occurring GGCX mutations are associated with multiple distinct clinical phenotypes. However, the genotype–phenotype correlation of GGCX remains elusive. Here, we systematically examined the effect of all naturally occurring GGCX mutations on the carboxylation of 3 structure–function distinct VKD proteins in a cellular environment. GGCX mutations were transiently introduced into GGCX-deficient human embryonic kidney 293 cells stably expressing chimeric coagulation factor, matrix Gla protein (MGP), or osteocalcin as VKD reporter proteins, and then the carboxylation efficiency of these reporter proteins was evaluated. Our results show that GGCX mutations differentially affect the carboxylation of these reporter proteins and the efficiency of using vitamin K as a cofactor. Carboxylation of these reporter proteins by a C-terminal truncation mutation (R704X) implies that GGCX’s C terminus plays a critical role in the binding of osteocalcin but not in the binding of coagulation factors and MGP. This has been confirmed by probing the protein–protein interaction between GGCX and its protein substrates in live cells using bimolecular fluorescence complementation and chemical cross-linking assays. Additionally, using a minigene splicing assay, we demonstrated that several GGCX missense mutations affect GGCX’s pre–messenger RNA splicing rather than altering the corresponding amino acid residues. Results from this study interpreted the correlation of GGCX’s genotype and its clinical phenotypes and clarified why vitamin K administration rectified bleeding disorders but not nonbleeding disorders.
Region-specific brain area reductions and increased cholecystokinin positive neurons in diabetic OLETF rats: implication for anxiety-like behavior
Authors: Ochi Ryosuke , Fujita Naoto , Goto Natsuki , Nguyen Son Tien , Le Duc Trung , Matsushita Kojiro , Ono Taketoshi , Nishijo Hisao , Urakawa Susumu 
Published: September 2020

AbstractMetabolic disorders can induce psychiatric comorbidities. Both brain and neuronal composition imbalances reportedly induce an anxiety-like phenotype. We hypothesized that alterations of localized brain areas and cholecystokinin (CCK) and parvalbumin (PV) expression could induce anxiety-like behavior in type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Twenty-week-old OLETF and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats were used. The areas of corticolimbic regions were smaller in OLETF rats. The densities of CCK positive neurons in the lateral and basolateral amygdala, hippocampal cornu ammonis area 2, and prelimbic cortex were higher in OLETF rats. The densities of PV positive neurons were comparable between OLETF and LETO rats. Locomotion in the center zone in the open field test was lower in OLETF rats. These results suggest that imbalances of specific brain region areas and neuronal compositions in emotion-related areas increase the prevalence of anxiety-like behaviors in OLETF rats.
Variable-order reference-free variant discovery with the Burrows-Wheeler Transform
Authors: Prezza Nicola , Pisanti Nadia , Sciortino Marinella , Rosone Giovanna 
Published: September 2020

Abstract
Background
In [Prezza et al., AMB 2019], a new reference-free and alignment-free framework for the detection of SNPs was suggested and tested. The framework, based on the Burrows-Wheeler Transform (BWT), significantly improves sensitivity and precision of previous de Bruijn graphs based tools by overcoming several of their limitations, namely: (i) the need to establish a fixed value, usually small, for the order k, (ii) the loss of important information such as k-mer coverage and adjacency of k-mers within the same read, and (iii) bad performance in repeated regions longer than k bases. The preliminary tool, however, was able to identify only SNPs and it was too slow and memory consuming due to the use of additional heavy data structures (namely, the Suffix and LCP arrays), besides the BWT.

Results
In this paper, we introduce a new algorithm and the corresponding tool ebwt2InDel that (i) extend the framework of [Prezza et al., AMB 2019] to detect also INDELs, and (ii) implements recent algorithmic findings that allow to perform the whole analysis using just the BWT, thus reducing the working space by one order of magnitude and allowing the analysis of full genomes. Finally, we describe a simple strategy for effectively parallelizing our tool for SNP detection only. On a 24-cores machine, the parallel version of our tool is one order of magnitude faster than the sequential one. The tool ebwt2InDel is available at github.com/nicolaprezza/ebwt2InDel.

Conclusions
Results on a synthetic dataset covered at 30x (Human chromosome 1) show that our tool is indeed able to find up to 83% of the SNPs and 72% of the existing INDELs. These percentages considerably improve the 71% of SNPs and 51% of INDELs found by the state-of-the art tool based on de Bruijn graphs. We furthermore report results on larger (real) Human whole-genome sequencing experiments. Also in these cases, our tool exhibits a much higher sensitivity than the state-of-the art tool.
Large-scale prediction and analysis of protein sub-mitochondrial localization with DeepMito
Authors: Savojardo Castrense , Martelli Pier Luigi , Tartari Giacomo , Casadio Rita 
Published: September 2020

Abstract
Background
The prediction of protein subcellular localization is a key step of the big effort towards protein functional annotation. Many computational methods exist to identify high-level protein subcellular compartments such as nucleus, cytoplasm or organelles. However, many organelles, like mitochondria, have their own internal compartmentalization. Knowing the precise location of a protein inside mitochondria is crucial for its accurate functional characterization. We recently developed DeepMito, a new method based on a 1-Dimensional Convolutional Neural Network (1D-CNN) architecture outperforming other similar approaches available in literature.

Results
Here, we explore the adoption of DeepMito for the large-scale annotation of four sub-mitochondrial localizations on mitochondrial proteomes of five different species, including human, mouse, fly, yeast and Arabidopsis thaliana. A significant fraction of the proteins from these organisms lacked experimental information about sub-mitochondrial localization. We adopted DeepMito to fill the gap, providing complete characterization of protein localization at sub-mitochondrial level for each protein of the five proteomes. Moreover, we identified novel mitochondrial proteins fishing on the set of proteins lacking any subcellular localization annotation using available state-of-the-art subcellular localization predictors. We finally performed additional functional characterization of proteins predicted by DeepMito as localized into the four different sub-mitochondrial compartments using both available experimental and predicted GO terms. All data generated in this study were collected into a database called DeepMitoDB (available at http://busca.biocomp.unibo.it/deepmitodb), providing complete functional characterization of 4307 mitochondrial proteins from the five species.

Conclusions
DeepMitoDB offers a comprehensive view of mitochondrial proteins, including experimental and predicted fine-grain sub-cellular localization and annotated and predicted functional annotations. The database complements other similar resources providing characterization of new proteins. Furthermore, it is also unique in including localization information at the sub-mitochondrial level. For this reason, we believe that DeepMitoDB can be a valuable resource for mitochondrial research.
An improvement of ComiR algorithm for microRNA target prediction by exploiting coding region sequences of mRNAs
Authors: Bertolazzi Giorgio , Benos Panayiotis V. , Tumminello Michele , Coronnello Claudia 
Published: September 2020

AbstractMicroRNA are small non-coding RNAs that post-transcriptionally regulate the expression levels of messenger RNAs. MicroRNA regulation activity depends on the recognition of binding sites located on mRNA molecules. ComiR is a web tool realized to predict the targets of a set of microRNAs, starting from their expression profile. ComiR was trained with the information regarding binding sites in the 3’utr region, by using a reliable dataset containing the targets of endogenously expressed microRNA in D. melanogaster S2 cells. This dataset was obtained by comparing the results from two different experimental approaches, i.e., inhibition, and immunoprecipitation of the AGO1 protein--a component of the microRNA induced silencing complex.In this work, we tested whether including coding region binding sites in ComiR algorithm improves the performance of the tool in predicting microRNA targets. We focused the analysis on the D. melanogaster species and updated the ComiR underlying database with the currently available releases of mRNA and microRNA sequences. As a result, we find that ComiR algorithm trained with the information related to the coding regions is more efficient in predicting the microRNA targets, with respect to the algorithm trained with 3’utr information. On the other hand, we show that 3’utr based predictions can be seen as complementary to the coding region based predictions, which suggests that both predictions, from 3’utr and coding regions, should be considered in comprehensive analysis.Furthermore, we observed that the lists of targets obtained by analyzing data from one experimental approach only, that is, inhibition or immunoprecipitation of AGO1, are not reliable enough to test the performance of our microRNA target prediction algorithm. Further analysis will be conducted to investigate the effectiveness of the tool with data from other species, provided that validated datasets, as obtained from the comparison of RISC proteins inhibition and immunoprecipitation experiments, will be available for the same samples. Finally, we propose to upgrade the existing ComiR web-tool by including the coding region based trained model, available together with the 3’utr based one.
miRTissue ce: extending miRTissue web service with the analysis of ceRNA-ceRNA interactions
Authors: Fiannaca Antonino , Paglia Laura La , Rosa Massimo La , Rizzo Riccardo , Urso Alfonso 
Published: September 2020

Abstract
Background
Non-coding RNAs include different classes of molecules with regulatory functions. The most studied are microRNAs (miRNAs) that act directly inhibiting mRNA expression or protein translation through the interaction with a miRNAs-response element. Other RNA molecules participate in the complex network of gene regulation. They behave as competitive endogenous RNA (ceRNA), acting as natural miRNA sponges to inhibit miRNA functions and modulate the expression of RNA messenger (mRNA). It became evident that understanding the ceRNA–miRNA–mRNA crosstalk would increase the functional information across the transcriptome, contributing to identify new potential biomarkers for translational medicine.

Results
We present miRTissue ce, an improvement of our original miRTissue web service. By introducing a novel computational pipeline, miRTissue ce provides an easy way to search for ceRNA interactions in several cancer tissue types. Moreover it extends the functionalities of previous miRTissue release about miRNA-target interaction in order to provide a complete insight about miRNA mediated regulation processes. miRTissue ce is freely available at http://tblab.pa.icar.cnr.it/mirtissue.html.

Conclusions
The study of ceRNA networks and its dynamics in cancer tissue could be applied in many fields of translational biology, as the investigation of new cancer biomarker, both diagnostic and prognostic, and also in the investigation of new therapeutic strategies of intervention. In this scenario, miRTissue ce can offer a powerful instrument for the analysis and characterization of ceRNA-ceRNA interactions in different tissue types, representing a fundamental step in order to understand more complex regulation mechanisms.