bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of CXCR4 tropism and CCR5-tropic resistance in treatment-experienced participants receiving maraviroc in the 48-week MOTIVATE 1 and 2 trials
Authors: Jubb Becky , Lewis Marilyn , McFadyen Lynn , Simpson Paul , Mori Julie , Chan Phylinda , Weatherley Barry , van der Ryst Elna , Westby Mike , Craig Charles 
Published: December 2019

Maraviroc blocks HIV-1 entry into CD4+ cells by interrupting the interaction between viral gp120 and cell-surface CCR5. Resistance to CCR5 antagonist–mediated inhibition can develop by unmasking pre-existing CXCR4-using virus or through selection of CCR5-tropic resistant virus, characterized by plateaus in maximum percent inhibition <95%. Here, we examine viral escape in maraviroc-treated participants during virologic failure through Week 48 in the MOTIVATE 1 and 2 trials. Resistance was assessed relative to number of active drugs in participants’ optimized background therapy, pharmacokinetic adherence markers, Baseline demographic data, HIV-1 RNA and CD4+ counts. For participants with R5 virus confirmed ( post hoc) at Screening, Baseline genotypic weighted optimized background therapy susceptibility scores (gwOBTSS) were assigned where possible. Through Week 48, 219/392 (56%) participants with an assigned gwOBTSS achieved a virologic response. Of those remaining, 48/392 (12%) had CXCR4-using virus; 58/392 (15%) had R5 virus (maraviroc sensitive: n = 35/392, 9%; maraviroc resistant: n = 18/392, 5%; undeterminable: n = 5/392, 1%) and 67/392 (17%) had no failure tropism result. When optimized background therapy provided limited support to maraviroc (gwOBTSS <2), 143/286 (50%) responded to therapy, while 76/106 (72%) participants with gwOBTSS ≥2 responded ( p < 0.001). Resistance rates were highest for participants with gwOBTSS <2, accounting for 45/48 (94%) of total CXCR4-using emergence and 18/18 (100%) of total CCR5-tropic resistance. R5 viruses from participants with gwOBTSS ≥2 ( n = 10) were exclusively maraviroc sensitive; five of these participants had pharmacokinetic and/or pill-count markers of non-adherence. When co-administered with a fully active background regimen, maraviroc did not readily generate resistance in the clinical setting. Trial registry name: ClinicalTrials.gov ( https://clinicaltrials.gov/ ), NCT00098722 and NCT00098306
Incidence of Deep Venous Thrombosis Associated With Proximal Hamstring Rupture
Authors: Engler Ian D. , Bragg Jack T. , Miller Suzanne L. 
Published: December 2019

Background: Rates of deep venous thrombosis (DVT) have been studied for most common orthopaedic injuries. However, rates and risk factors have not been published for proximal hamstring injuries. Purpose: To determine the incidence of symptomatic DVT associated with proximal hamstring rupture and associations with prophylactic anticoagulation. Study Design: Case series; Level of evidence, 4. Methods: Inclusion criteria included all complete and, in a separate cohort, partial proximal hamstring ruptures treated by the senior author from 2007 through 2018 with at least 8 weeks of follow-up. Tendinopathy without tear was excluded. No DVT screening was performed. Charts of patients with symptomatic DVT were reviewed for the treatment method, the presence of imaging-confirmed DVT or pulmonary embolism, and risk factors for DVT. No patients received postinjury DVT prophylaxis. Surgical patients were routinely instructed to take aspirin (325 mg bid) or apixaban (2.5 mg bid) for 4 weeks. Patients with risk factors for DVT received enoxaparin (40 mg daily) for 2 weeks followed by aspirin (325 mg bid) for 2 weeks. Results: A total of 144 complete proximal hamstring ruptures were included: 132 treated operatively and 12 treated nonoperatively. There were 10 DVTs associated with the injury, for an overall rate of 6.9%. Five of the DVTs were diagnosed preoperatively in patients who had not received DVT prophylaxis; the other 5 were diagnosed postoperatively in patients on DVT prophylaxis. Six of the 10 DVTs had identifiable risk factors. All patients with postoperatively diagnosed DVTs were on prophylactic aspirin or enoxaparin. In the partial proximal hamstring rupture cohort of 114 ruptures, there were no DVTs. Conclusion: There is a high incidence of DVT associated with complete proximal hamstring ruptures (6.9%) despite many patients receiving DVT prophylaxis. This is substantially higher than that in other lower extremity injuries. Clinicians should have a high index of suspicion for DVT after these injuries, and postinjury DVT prophylaxis may be warranted.
Retears of the Rotator Cuff: An Ultrasonographic Assessment During the First Postoperative Year
Authors: Aguado Giussepe , Obando Daniel Vernaza , Herrera Gilberto A. , Ramirez Alejandro , Llinás Paulo J. 
Published: December 2019

Background: Surgical repair of rotator cuff (RC) tears is an effective treatment option. However, the prevalence of recurrent ruptures is high. Hypothesis: Recurrent tears are a frequent complication of surgical repair of RC tears. Their incidence might be influenced by factors such as the patient’s age and size of the initial tear. Study Design: Case series; Level of evidence, 4. Methods: Data from 90 adult patients who underwent arthroscopic RC repair between 2014 and 2017 and underwent an ultrasound examination 6 to 12 months after surgery were analyzed retrospectively. Massive tears were repaired using a double-row technique, and nonmassive tears were repaired with a single-row technique. Clinical records were reviewed for demographic information. Results: All patients (57.8% women; 42.2% men) were older than 18 years (mean, 58.9 years). Of these patients, 30.0% (27/90) had massive tears, which were primarily found in patients ≥60 years (74.1%; 20/27). Complete healing was seen in 74.5% of all repairs during follow-up. A total of 23 patients (25.5%) had retears (13 complete; 10 partial), which were diagnosed by ultrasound imaging 6 to 12 months after the initial surgery. The occurrence of retears was more prevalent in patients with massive tears than in patients with nonmassive tears (40.7% vs 19.0%, respectively); the difference was statistically significant ( P = .03). Reruptures occurred in 50.0% of patients older than 60 years with massive tears. Although patients older than 60 years had more recurrent tears (32.6%) compared with younger patients (18.2%), the difference was not statistically significant ( P = .12). Conclusion: One-quarter of the patients who had undergone surgical repair of an RC tear had recurrent ruptures. There was a statistically significant association between the initial massive tear and a retear. Patients older than 60 years showed a higher recurrence rate, but this difference lacked statistical significance. Reruptures occurred in 50.0% of patients older than 60 years with massive tears.
Unilateral Multiple Extramedullary Plasmacytoma of the Choroid and Conjunctiva: A Case Report
Authors: Mohamed Shymaa , Silvasi Truman , Kubat Anthony , Aaberg Thomas 
Published: December 2019

Purpose: We report a case of multiple extramedullary plasmacytoma (EMP) of the choroid and conjunctiva as a sign of multiple myeloma (MM) relapse. Methods: An observational case report with clinicopathologic correlation is presented. Results: A 45-year-old man with a 2.5-year history of MM presented with left eye pain. Examination revealed a conjunctival nodule and choroidal infiltrate in the left eye. Excisional biopsy demonstrated plasmacytoma of the conjunctiva and choroid. Despite radiotherapy and chemotherapy, multiple EMP recurred and the patient died 8 months after initial presentation. Conclusions: Multiple EMP of the choroid and conjunctiva has a poor prognosis and can present as a sign of MM relapse. Our imaging demonstrates the clinical manifestations of this tumor and can aid future diagnoses. Our radiation dose (20 Gy) was inadequate, which is an important reportable factor for future patients.
Standardised shorter regimens versus individualised longer regimens for rifampin- or multidrug-resistant tuberculosis
Authors: Abidi Syed , Achar Jay , Assao Neino Mourtala Mohamed , Bang Didi , Benedetti Andrea , Brode Sarah , Campbell Jonathon R. , Casas Esther C. , Conradie Francesca , Dravniece Gunta , du Cros Philipp , Falzon Dennis , Jaramillo Ernesto , Kuaban Christopher , Lan Zhiyi , Lange Christoph , Li Pei Zhi , Makhmudova Mavluda , Maug Aung Kya Jai , Menzies Dick , Migliori Giovanni Battista , Miller Ann , Myrzaliev Bakyt , Ndjeka Norbert , Noeske Jürgen , Parpieva Nargiza , Piubello Alberto , Schwoebel Valérie , Sikhondze Welile , Singla Rupak , Souleymane Mahamadou Bassirou , Trébucq Arnaud , Van Deun Armand , Viney Kerri , Weyer Karin , Zhang Betty Jingxuan , Ahmad Khan Faiz 
Published: December 2019

We sought to compare the effectiveness of two World Health Organization (WHO)-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis (TB): a standardised regimen of 9–12 months (the “shorter regimen”) and individualised regimens of ≥20 months (“longer regimens”).We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD −0.15, 95% CI −0.17– −0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0–0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07–0.16), prothionamide/ethionamide (aRD 0.07, 95% CI −0.01–0.16) or ethambutol (aRD 0.09, 95% CI 0.04–0.13).In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
Effects of suboptimal adherence of CPAP therapy on symptoms of obstructive sleep apnoea: a randomised, double-blind, controlled trial
Authors: Gaisl Thomas , Rejmer Protazy , Thiel Sira , Haile Sarah R. , Osswald Martin , Roos Malgorzata , Bloch Konrad E. , Stradling John R. , Kohler Malcolm 
Published: December 2019

IntroductionContinuous positive airway pressure (CPAP) is currently the treatment of choice for sleepiness in patients with obstructive sleep apnoea (OSA); however, adherence is often thought to be suboptimal. We investigated the effects of suboptimal CPAP usage on objective and subjective sleepiness parameters in patients with OSA.Material and methodsIn this 2-week, parallel, double-blind, randomised controlled trial we enrolled moderate-to-severe OSA patients with excessive pre-treatment daytime sleepiness (Epworth sleepiness scale (ESS) score >10 points) who had suboptimal CPAP adherence over ≥12 months (mean nightly usage time 3–4 h). Patients were allocated through minimisation to either subtherapeutic CPAP (“sham CPAP”) or continuation of CPAP (“therapeutic CPAP”). A Bayesian analysis with historical priors calculated the posterior probability of superiority.ResultsBetween May, 2016 and November, 2018, 57 patients (aged 60±8 years, 79% male, 93% Caucasian) were allocated in total, and 52 who completed the study (50% in each arm) were included in the final analysis. The unadjusted ESS score increase was 2.4 points (95% CI 0.6–4.2, p=0.01) in the sham-CPAP group when compared to continuing therapeutic CPAP. The probability of superiority of therapeutic CPAP over sham CPAP was 90.4% for ESS, 90.1% for systolic blood pressure and 80.3% for diastolic blood pressure.ConclusionsPatients with moderate-to-severe OSA and daytime sleepiness are still getting a substantial benefit from suboptimal CPAP adherence, albeit not as much as they might get if they adhered more. Whether a similar statement can be made for even lower adherence levels remains to be established in future trials.
Biological representation of chemicals using latent target interaction profile
Authors: Ayed Mohamed , Lim Hansaim , Xie Lei 
Published: December 2019

Abstract
Background
Computational prediction of a phenotypic response upon the chemical perturbation on a biological system plays an important role in drug discovery, and many other applications. Chemical fingerprints are a widely used feature to build machine learning models. However, the fingerprints that are derived from chemical structures ignore the biological context, thus, they suffer from several problems such as the activity cliff and curse of dimensionality. Fundamentally, the chemical modulation of biological activities is a multi-scale process. It is the genome-wide chemical-target interactions that modulate chemical phenotypic responses. Thus, the genome-scale chemical-target interaction profile will more directly correlate with in vitro and in vivo activities than the chemical structure. Nevertheless, the scope of direct application of the chemical-target interaction profile is limited due to the severe incompleteness, biasness, and noisiness of bioassay data.

Results
To address the aforementioned problems, we developed a novel chemical representation method: Latent Target Interaction Profile (LTIP). LTIP embeds chemicals into a low dimensional continuous latent space that represents genome-scale chemical-target interactions. Subsequently LTIP can be used as a feature to build machine learning models. Using the drug sensitivity of cancer cell lines as a benchmark, we have shown that the LTIP robustly outperforms chemical fingerprints regardless of machine learning algorithms. Moreover, the LTIP is complementary with the chemical fingerprints. It is possible for us to combine LTIP with other fingerprints to further improve the performance of bioactivity prediction.

Conclusions
Our results demonstrate the potential of LTIP in particular and multi-scale modeling in general in predictive modeling of chemical modulation of biological activities.
DeepShape: estimating isoform-level ribosome abundance and distribution with Ribo-seq data
Authors: Cui Hongfei , Hu Hailin , Zeng Jianyang , Chen Ting 
Published: December 2019

Abstract
Background
Ribosome profiling brings insight to the process of translation. A basic step in profile construction at transcript level is to map Ribo-seq data to transcripts, and then assign a huge number of multiple-mapped reads to similar isoforms. Existing methods either discard the multiple mapped-reads, or allocate them randomly, or assign them proportionally according to transcript abundance estimated from RNA-seq data.

Results
Here we present DeepShape, an RNA-seq free computational method to estimate ribosome abundance of isoforms, and simultaneously compute their ribosome profiles using a deep learning model. Our simulation results demonstrate that DeepShape can provide more accurate estimations on both ribosome abundance and profiles when compared to state-of-the-art methods. We applied DeepShape to a set of Ribo-seq data from PC3 human prostate cancer cells with and without PP242 treatment. In the four cell invasion/metastasis genes that are translationally regulated by PP242 treatment, different isoforms show very different characteristics of translational efficiency and regulation patterns. Transcript level ribosome distributions were analyzed by “Codon Residence Index (CRI)” proposed in this study to investigate the relative speed that a ribosome moves on a codon compared to its synonymous codons. We observe consistent CRI patterns in PC3 cells. We found that the translation of several codons could be regulated by PP242 treatment.

Conclusion
In summary, we demonstrate that DeepShape can serve as a powerful tool for Ribo-seq data analysis.
SigUNet: signal peptide recognition based on semantic segmentation
Authors: Wu Jhe-Ming , Liu Yu-Chen , Chang Darby Tien-Hao 
Published: December 2019

Abstract
Background
Signal peptides play an important role in protein sorting, which is the mechanism whereby proteins are transported to their destination. Recognition of signal peptides is an important first step in determining the active locations and functions of proteins. Many computational methods have been proposed to facilitate signal peptide recognition. In recent years, the development of deep learning methods has seen significant advances in many research fields. However, most existing models for signal peptide recognition use one-hidden-layer neural networks or hidden Markov models, which are relatively simple in comparison with the deep neural networks that are used in other fields.

Results
This study proposes a convolutional neural network without fully connected layers, which is an important network improvement in computer vision. The proposed network is more complex in comparison with current signal peptide predictors. The experimental results show that the proposed network outperforms current signal peptide predictors on eukaryotic data. This study also demonstrates how model reduction and data augmentation helps the proposed network to predict bacterial data.

Conclusions
The study makes three contributions to this subject: (a) an accurate signal peptide recognizer is developed, (b) the potential to leverage advanced networks from other fields is demonstrated and (c) important modifications are proposed while adopting complex networks on signal peptide recognition.
Association between ALS and retroviruses: evidence from bioinformatics analysis
Authors: Klein Jon P. , Sun Zhifu , Staff Nathan P. 
Published: December 2019

AbstractBackgroundEmerging evidence suggests retroviruses play a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). Specifically, activation of ancient viral genes embedded in the human genome is theorized to lead to motor neuron degeneration. We explore whether connections exist between ALS and retroviruses through protein interaction networks (PIN) and pathway analysis, and consider the potential roles in drug target discovery. Protein database and pathway/network analytical software including Ingenuity Pathway BioProfiler, STRING, and CytoScape were utilized to identify overlapping protein interaction networks and extract core cluster (s) of retroviruses and ALS.ResultsTopological and statistical analysis of the ALS-PIN and retrovirus-PIN identified a shared, essential protein network and a core cluster with significant connections with both networks. The identified core cluster has three interleukin molecules IL10, Il-6 and IL-1B, a central apoptosis regulator TP53, and several major transcription regulators including MAPK1, ANXA5, SQSTM1, SREBF2, and FADD. Pathway enrichment analysis showed that this core cluster is associated with the glucocorticoid receptor singling and neuroinflammation signaling pathways. For confirmation purposes, we applied the same methodology to the West Nile and Polio virus, which demonstrated trivial connectivity with ALS, supporting the unique connection between ALS and retroviruses.ConclusionsBioinformatics analysis provides evidence to support pathological links between ALS and retroviral activation. The neuroinflammation and apoptotic regulation pathways are specifically implicated. The continuation and further analysis of large scale genome studies may prove useful in exploring genes important in retroviral activation and ALS, which may help discover new drug targets.
Bigram-PGK: phosphoglycerylation prediction using the technique of bigram probabilities of position specific scoring matrix
Authors: Chandra Abel , Sharma Alok , Dehzangi Abdollah , Shigemizu Daichi , Tsunoda Tatsuhiko 
Published: December 2019

Abstract
Background
The biological process known as post-translational modification (PTM) is a condition whereby proteomes are modified that affects normal cell biology, and hence the pathogenesis. A number of PTMs have been discovered in the recent years and lysine phosphoglycerylation is one of the fairly recent developments. Even with a large number of proteins being sequenced in the post-genomic era, the identification of phosphoglycerylation remains a big challenge due to factors such as cost, time consumption and inefficiency involved in the experimental efforts. To overcome this issue, computational techniques have emerged to accurately identify phosphoglycerylated lysine residues. However, the computational techniques proposed so far hold limitations to correctly predict this covalent modification.

Results
We propose a new predictor in this paper called Bigram-PGK which uses evolutionary information of amino acids to try and predict phosphoglycerylated sites. The benchmark dataset which contains experimentally labelled sites is employed for this purpose and profile bigram occurrences is calculated from position specific scoring matrices of amino acids in the protein sequences. The statistical measures of this work, such as sensitivity, specificity, precision, accuracy, Mathews correlation coefficient and area under ROC curve have been reported to be 0.9642, 0.8973, 0.8253, 0.9193, 0.8330, 0.9306, respectively.

Conclusions
The proposed predictor, based on the feature of evolutionary information and support vector machine classifier, has shown great potential to effectively predict phosphoglycerylated and non-phosphoglycerylated lysine residues when compared against the existing predictors. The data and software of this work can be acquired from https://github.com/abelavit/Bigram-PGK.