bluuebunny/crossref_metadata_2025_split huggingface dataset:
De Novo Versus Recurrent HER2-Positive Metastatic Breast Cancer: Patient Characteristics, Treatment, and Survival from the SystHERs Registry
Authors: Tripathy Debu , Brufsky Adam , Cobleigh Melody , Jahanzeb Mohammad , Kaufman Peter A. , Mason Ginny , O'Shaughnessy Joyce , Rugo Hope S. , Swain Sandra M. , Yardley Denise A. , Chu Laura , Li Haocheng , Antao Vincent , Hurvitz Sara A. 
Published: October 2019

Abstract

Background
Limited data exist describing real-world treatment of de novo and recurrent HER2-positive metastatic breast cancer (MBC).

Materials and Methods
The Systemic Therapies for HER2-Positive Metastatic Breast Cancer Study (SystHERs) was a fully enrolled (2012–2016), observational, prospective registry of patients with HER2-positive MBC. Patients aged ≥18 years and ≤6 months from HER2-positive MBC diagnosis were treated and assessed per their physician's standard practice. The primary endpoint was to characterize treatment patterns by de novo versus recurrent MBC status, compared descriptively. Secondary endpoints included patient characteristics, progression-free and overall survival (PFS and OS, by Kaplan-Meier method; hazard ratio [HR] and 95% confidence interval [CI] by Cox regression), and patient-reported outcomes.

Results
Among 977 eligible patients, 49.8% (n = 487) had de novo and 50.2% (n = 490) had recurrent disease. A higher proportion of de novo patients had hormone receptor–negative disease (34.9% vs. 24.9%), bone metastasis (57.1% vs. 45.9%), and/or liver metastasis (41.9% vs. 33.1%), and a lower proportion had central nervous system metastasis (4.3% vs. 13.5%). De novo patients received first-line regimens containing chemotherapy (89.7%), trastuzumab (95.7%), and pertuzumab (77.8%) more commonly than recurrent patients (80.0%, 85.9%, and 68.6%, respectively). De novo patients had longer median PFS (17.7 vs. 11.9 months; HR, 0.69; 95% CI, 0.59–0.80; p &lt; .0001) and OS (not estimable vs. 44.5 months; HR, 0.55; 95% CI, 0.44–0.69; p &lt; .0001).

Conclusion
Patients with de novo versus recurrent HER2-positive MBC exhibit different disease characteristics and survival durations, suggesting these groups have distinct outcomes. These differences may affect future clinical trial design. Clinical trial identification number. NCT01615068 (clinicaltrials.gov).
The Effect of Combination Iron Chelating Agents on Reducing the Severity Grading of Heart and Liver Iron Overload in β-Thalassemia Patients
Authors: Ghanavat Majid , Fazeli Varzaneh Alireza , Reisi Nahid 
Published: October 2019

Background: Deferasirox (DFX), Deferoxamine (DFO), and Deferiprone (DFP) are iron chelators that can be used in thalassemic patients with iron overload.
Materials and Methods: This clinical trial was performed on 108 thalassemic patients who were randomly divided into group A (n=54) and B (n=54). Group A received combination of DFX and DFP, and group B received DFO and DFP for six months. Serum ferritin level was measured at the beginning of the study, 3, and 6 months after the treatment; The heart and liver iron deposition rates were also measured at the beginning of the study, and 6 months after the treatment in both groups and compared using Magnetic Resonance Imaging T2 plus (MRI T2*).
Results: The mean age of patients in group A and B was 17.29±4.3 and 17.89±5.61 years old, respectively. Serum ferritin level significantly reduced after the treatment (Serum ferritin level at baseline, 3, and 6 months after the treatment in Group A: 2476.25±1289.32, 2089.62±1051.64 and 1290.22±724.78 ng/ml, respectively; in Group B: 2044.63±989.82, 1341.30±887.62 and 1229.41±701.22 ng/ml, respectively) (p<0.01, for both groups). MRI T2* heart and liver was also improved at the end of the study in both groups (p<0.01, for both groups). However, the combination of DFO/DFP significantly decreased severity grades of liver iron deposition in comparison to DFX/DFP regimen after six months (p<0.01).
Conclusion: The results of the present study indicated that both combination therapies of DFO/DFP and DFX/DFP could improve heart and liver MRI T2*. However, DFO/DFP combination therapy was more effective in reducing the severity grades of liver iron deposition.
Revisiting the International Normalized Ratio Threshold for Bleeding Risk and Mortality in Primary Total Hip Arthroplasty
Authors: Rudasill Sarah E. , Liu Jiabin , Kamath Atul F. 
Published: October 2019

Background:
Efforts to identify preoperative risk factors for primary total hip arthroplasty have amplified with its increasing incidence. The international normalized ratio (INR) is 1 measure that may influence postoperative outcomes. This study of a national database assessed whether there exists an association between preoperative INR and postoperative bleeding and mortality among patients who underwent primary total hip arthroplasty.

Methods:
We retrospectively analyzed 17,567 adult patients who underwent primary total hip arthroplasty in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) between 2005 and 2016. Patients were stratified by preoperative INR into 4 groups: INR <1.0, 1.0 to <1.25, 1.25 to <1.5, and ≥1.5. Bleeding necessitating transfusion was the primary outcome, and secondary outcomes included mortality, infection, and readmission. Multivariable logistic regressions controlled for baseline differences.

Results:
Among the patients who underwent total hip arthroplasty, 20.5% had INR <1.0, 73.6% had INR 1.0 to <1.25, 4.2% had INR 1.25 to <1.5, and 1.8% had INR ≥1.5. Mortality increased incrementally from 0.3% for INR <1.0 to 4.9% for INR ≥1.5 (p < 0.001), and bleeding risk increased from 13.2% for INR <1.0 to 29.3% for INR ≥1.5 (p < 0.001). After adjustment, bleeding risk was increased for INR 1.25 to <1.5 (odds ratio [OR], 1.55 [95% confidence interval (CI), 1.26 to 1.92]) and INR ≥1.5 (OR, 1.55 [95% CI, 1.15 to 2.08]) compared with INR <1.0. The only group associated with increased mortality was INR ≥1.5 (OR, 2.69 [95% CI, 1.07 to 6.76]). The length of stay significantly increased with increasing INR, from 3.6 to 6.3 days (p < 0.001).

Conclusions:
This study found a significant, independent effect between increased preoperative INR and increased bleeding and mortality. Bleeding risk becomes evident at INR ≥1.25, and those patients with INR ≥1.5 are at significantly increased risk of mortality.

Level of Evidence:
Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Fast Starters, Slow Starters, and Late Dippers: Trajectories of Patient-Reported Outcomes After Total Hip Arthroplasty
Authors: Hesseling B. , Mathijssen N.M.C. , van Steenbergen L.N. , Melles M. , Vehmeijer S.B.W. , Porsius J.T. 
Published: October 2019

Background:
The purpose of this study was to explore whether subgroups of patients with different functional recovery trajectories after total hip arthroplasty can be discerned, as well as their predictors, using data from the Dutch Arthroplasty Register (Landelijke Registratie Orthopedische Implantaten [LROI]).

Methods:
We retrospectively reviewed prospectively collected Oxford Hip Scores (OHS) up to 1 year postoperatively for patients who had undergone a primary total hip arthroplasty. Latent class growth modeling was used to classify subgroups of patients according to the trajectory of functional recovery represented by the patients’ OHS. We used multivariable multinomial logistic regression analysis to explore factors associated with class membership.

Results:
A total of 6,030 patients were analyzed. Latent class growth modeling identified fast starters (fast initial improvement, high 12-month scores; 87.7%), slow starters (no initial change and subsequent improvement; 4.6%), and late dippers (initial improvement and subsequent deterioration; 7.7%). Factors associated with slow starters were female sex (odds ratio [OR], 1.63 [95% confidence interval (CI), 1.14 to 2.33]) and smoking (OR, 1.95 [95% CI, 1.26 to 3.03]); an anterior approach (OR, 0.47 [95% CI, 0.29 to 0.78]) had a protective effect against a less favorable response. Factors associated with late dippers were age of >75 years (OR, 1.62 [95% CI, 1.22 to 2.15]), smoking (OR, 1.68 [95% CI, 1.17 to 2.42]), American Society of Anesthesiologists (ASA) grade of III or IV (OR, 1.41 [95% CI, 1.05 to 1.91]), obesity (OR, 1.96 [95% CI, 1.43 to 2.69]), poorer EuroQol-5 Dimensions (EQ-5D) Self-Care (OR, 1.41 [95% CI, 1.09 to 1.82] for “some problems” and OR, 2.90 [95% CI, 1.39 to 6.03] for “unable”), poorer EQ-5D Anxiety/Depression (OR, 1.31 [95% CI, 1.00 to 1.71] for “moderately” and OR, 1.86 [95% CI, 1.06 to 3.24] for “extremely”), poorer EQ-5D visual analog scale (OR, 0.91 [95% CI, 0.86 to 0.97] per 10 points), direct lateral approach (OR, 2.18 [95% CI, 1.58 to 3.02]), and hybrid fixation with a cemented acetabular implant (OR, 1.79 [95% CI, 1.00 to 3.21]).

Conclusions:
We discerned fast starters, slow starters, and late dippers after total hip arthroplasty. Female sex, older age, obesity, higher ASA grades, and worse EQ-5D scores were associated with a less favorable response to total hip arthroplasty, as well as hybrid fixation (cemented acetabular implant) and direct lateral approach. Anterior approach had a protective effect against a less favorable response. However, all subgroups experienced functional improvement following total hip arthroplasty.

Level of Evidence:
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
An Integrated Machine-Learning Approach to Shale-Gas Supply-Chain Optimization and Refrac Candidate Identification
Authors: Asala Hope I. , Chebeir Jorge A. , Manee Vidhyadhar , Gupta Ipsita , Dahi–Taleghani Arash , Romagnoli Jose A. 
Published: October 2019

Summary
The unsteady recovery of oil and gas prices in early 2017 led to an increase in drilling and hydraulic–fracturing operations in liquid–rich shale plays in North America. As field–development strategies continue to evolve, refracturing and infill–well drilling must be carefully combined to optimize shale–project profitability. Moreover, operators must bear in mind the undulating natural–gas demands persisting in an oversupplied shale–gas environment. In this paper, we use data–driven approaches to predict successful refracturing candidates and local gas demand for the second–tier optimization of a shale–gas supply–chain network.
A strategic–planning (SP) model is developed for optimizing the net present value (NPV) of a case–study shale–gas network in the Marcellus Play. This SP model uses a mixed–integer–nonlinear–programming (MINLP) formulation developed in the General Algebraic Modeling System (GAMS, Release 27.1.0.2019). This model relies directly on input from reservoir simulation, local–gas–demand forecast, water–availability forecast, and natural–gas and West Texas Intermediate (WTI) crude–oil price forecasts.
Before reservoir simulation, machine learning (ML) is used to predict successful refracturing candidates, using a feed–forward neural network (NN), random–forest (RF) classifier, and a t–distributed stochastic–neighbor–embedding (t–SNE) visualization technique. Using the obtained results, best–practice field–development strategies are implemented in the area of interest (AOI) using reservoir simulation. Local gas demand is forecasted using a long–short–term–memory (LSTM) recurrent NN (RNN) that uses a multivariate data set created from local and global variables affecting shale–gas demand. A water–management structure is also developed for the optimization framework.
Using a 300–well data set (with 17 input features), successful refracturing candidates were proposed according to the joint outcome of an optimal 17/23/128/2 feed–forward NN, a t–SNE plot, and a techno–economic review. After ranking F1 scores, the developed NN outperforms the RF and support–vector–machine (SVM) algorithms for frac/refrac–well classification. The developed 32/256/128/120 LSTM model showed at least a 93% (±1%) prediction performance using three or five input features. The results illustrate the ability of the developed LSTM model to accurately predict local gas demands during periods of high or low gas demand.
After SP optimization over a 10–year planning horizon, the economic results indicate an NPV of USD 481.945 million, using the proposed physics–data–driven–based approach. An NPV of USD 611.22 million is obtained when no ML was used. The results reveal that the application of ML to strategic planning can prevent erroneous feedback of project profitability while allowing early–time decision making that maximizes shale–asset NPV.
Multiscale Reconstruction of Vuggy Carbonates by Pore-Network Modeling and Image-Based Technique
Authors: Sadeghnejad Saeid , Gostick Jeff 
Published: October 2019

Summary
Vugular carbonate rocks have a complicated flow behavior because of their multimodal porosity system, with different interconnectivity at the pore scale. In this study, a new hybrid algorithm to reconstruct a bimodal vugular porous medium is introduced by coupling the pore-network modeling approach (i.e., stochastic) with the image-based network technique (i.e., process-based). This work implements image-processing techniques to generate a lattice-based network of secondary porosity (i.e., vugs) on top of an initial pore-network model at the pore scale. The resulting multiscale model is designed to preserve vug-to-vug and vug-to-pore connectivity of overlapping vugs. Modifying the effective conductance of the overlapped vugs enables the calculation of permeability of the dual-porosity network by applying mass conservation and the Poiseuille law. The method is validated on samples from an Iranian carbonate formation. The matrix micropores obtained from the mercury-intrusion laboratory measurements are statistically reconstructed by a Nelder-Mead optimization algorithm. Our results show that during the addition of vugs into a network, the absolute permeability of the network increases monotonically with rising porosity before vug percolation. However, once vuggy pores percolate, the absolute permeability of the network increases tremendously. Moreover, the availability of vugs makes the network structure more complex as determined by the off-diagonal complexity measure. The results of this study help in understanding the behavior of vuggy formations observed in carbonate reservoirs.
Influence of Virtual Reality on Visual Parameters: Immersive Versus Non-Immersive Mode
Authors: Yoon Hyeon Jeong , Kim Jonghwa , Park Sang Woo , Heo Hwan 
Published: October 2019

Abstract
Background : To investigate the differences in refraction, accommodative factors, visual parameters, and subjective symptoms after using two types of virtual reality (VR) content with different depths perception.
Methods : Twenty-three volunteers, who played VR games in two modes (immersive and non-immersive) for 30 min, were enrolled. Visual parameters were examined before and after using VR. Accommodative factors were measured using static and dynamic methods. Subjective symptoms were assessed using a questionnaire. Differences according to VR content were compared, and correlations between each visual parameter were analyzed.
Results : There were no changes in refraction or accommodative factors after use of the VR. However, there was a significant increase in the near point of accommodation (NPA), the near point of convergence (NPC), and subjective symptom scores after using the immersive mode. Correlation analysis revealed a positive correlation between baseline values of near exophoria and mean accommodative lag of the dominant eye, and also revealed a negative correlation between NPA and mean accommodative lag in the non-dominant eye.
Conclusions : The use of VR for 30 min increased NPA and NPC, especially after the immersive mode was used. In addition, higher exophoria and smaller NPA is associated with increased accommodative lag after using VR.
Tamoxifen in Duchenne muscular dystrophy (TAMDMD): study protocol for a multicenter, randomized, placebo-controlled, double-blind phase 3 trial
Authors: Nagy Sara , Hafner Patricia , Schmidt Simone , Rubino-Nacht Daniela , Schädelin Sabine , Bieri Oliver , Fischer Dirk 
Published: October 2019

Abstract
BACKGROUND Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disorder of childhood with a devastating disease course. Several targeted gene therapies and molecular approaches have been or are currently tested in clinical trials; however, a causative therapy is still not available and best supportive care is limited to oral glucocorticoids with numerous long-term side effects. Tamoxifen is a selective estrogen receptor regulator, and shows besides its antitumor activity also antioxidant actions and regulatory roles in the calcium homeostasis. In a mouse model of DMD, oral tamoxifen significantly improved muscle strength and reduced muscle fatigue. This multicenter, randomized, double-blind, placebo controlled phase 3 trial aims to demonstrate safety and efficacy of tamoxifen over placebo in pediatric patients with DMD. After completion of the double-blind phase, an open label extension of the study will be offered to all participants. METHODS/DESIGN At least 71 ambulant and up to 20 non-ambulant patients with DMD are planned to be enrolled at multiple European sites. Patients will be randomly assigned to receive either tamoxifen 20mg or placebo daily over 48 weeks. In the open-label extension phase, all patients will be offered to receive tamoxifen for further 48 weeks. The primary endpoint of the double-blind phase is defined as the change of the D1 domain of the motor function measure in ambulant patients or a change of the D2 domain in non-ambulant patients under tamoxifen compared to placebo. Secondary outcome measures include change in timed function tests, quantitative muscle testing, and quantitative MRI of thigh muscles. Laboratory analyses including biomarkers of tamoxifen metabolism and muscle dystrophy will also be assessed. DISCUSSION The aim of the study is to investigate whether tamoxifen can reduce disease progression in ambulant and non-ambulant DMD patients over 48 weeks. Motor function measure comprises the primary endpoint, whereas further clinical and radiological assessments and laboratory biomarkers are performed to provide more data on safety and efficacy. An adjacent open label extension phase is planned to test if earlier initiation of the treatment with tamoxifen (verum arm of double blind phase) compared to a delayed start can reduce disease progression more efficiently.
Genetic deletion of Sphk2 confers protection against Pseudomonas aeruginosa mediated differential expression of genes related to virulent infection and inflammation in mouse lung
Authors: Ebenezer David Lenin , Fu Panfeng , Krishnan Yashaswin , Maienschein-Cline Mark , Hu Hong , Jung Segun , Madduri Ravi , Arbieva Zarema , Harijith Anantha , Natarajan Viswanathan 
Published: October 2019

Abstract
BACKGROUND
Pseudomonas aeruginosa (PA) is an opportunistic Gram-negative bacterium that causes serious life threatening and nosocomial infections including pneumonia. PA has the ability to alter host genome to facilitate its invasion, thus increasing the virulence of the organism. Sphingosine-1- phosphate (S1P), a bioactive lipid, is known to play a key role in facilitating infection. Sphingosine kinases (SPHK) 1&2 phosphorylate sphingosine to generate S1P in mammalian cells. We reported earlier that Sphk2-/- mice offered significant protection against lung inflammation, compared to wild type (WT) animals. Therefore, we profiled the differential expression of genes between the protected group of Sphk2-/- and the wild type controls to better understand the underlying protective mechanisms related to the Sphk2 deletion in lung inflammatory injury. Whole transcriptome shotgun sequencing (RNA-Seq) was performed on mouse lung tissue using NextSeq 500 sequencing system.
RESULTS: Two-way analysis of variance (ANOVA) analysis was performed and differentially expressed genes following PA infection were identified using whole transcriptome of Sphk2-/- mice and their WT counterparts. Pathway (PW) enrichment analyses of the RNA seq data identified several signaling pathways that are likely to play a crucial role in pneumonia caused by PA such as those involved in: 1. Immune response to PA infection and NF-κB signal transduction; 2. PKC signal transduction; 3. Impact on epigenetic regulation; 4. Epithelial sodium channel pathway; 5. Mucin expression; and 6. Bacterial infection related pathways.
Our genomic data suggests a potential role for SPHK2 in PA-induced pneumonia through elevated expression of inflammatory genes in lung tissue. Further, validation by RT-PCR on 10 differentially expressed genes showed 100% concordance in terms of vectoral changes as well as significant fold change.
CONCLUSION: Using Sphk2-/- mice and differential gene expression analysis, we have shown here that S1P/SPHK2 signaling could play a key role in promoting PA pneumonia. The identified genes promote inflammation and suppress others that naturally inhibit inflammation and host defense. Thus, targeting SPHK2/S1P signaling in PA-induced lung inflammation could serve as a potential therapy to combat PA-induced pneumonia.
Key Words: Pseudomonas aeruginosa; Lung infection; Sphingosine kinase 2; Sphingolipids; Gene Profiling; Resistance to Infection
Arts, mental distress, mental health functioning &amp; life satisfaction: fixed effects analyses of a nationally-representative panel study
Authors: Wang Senhu , Mak Hei Wan , Fancourt Daisy 
Published: October 2019

Abstract
Background . Arts engagement within communities is ubiquitous across cultures globally and previous research has suggested its benefits for mental health and wellbeing. However, it remains unclear whether these benefits are driven by arts engagement itself or by important confounders such as socio-economic status (SES), childhood arts engagement, previous mental health, personality, or self-selection bias. The aim of this study is to use fixed effects models that account for unidentified time-constant confounding measures to examine the longitudinal association between arts (frequency of both arts participation and cultural attendance), mental distress, mental health functioning and life satisfaction.
Methods . Data from 23,660 individuals (with a mean age of 47 years) included in the UK Understanding Society wave 2 (2010-2012) and wave 5 (2013-2015) were analyzed. Aside from controlling for all time-constant variables using the fixed-effects models, we additionally adjusted for time-varying demographic factors (e.g. age and marital status), health behaviors and social support variables.
Results . After controlling for all time-constant variables and identified time-varying confounders, frequent arts participation and cultural attendance were associated with lower levels of mental distress and higher levels of life satisfaction, with arts participation additionally associated with better mental health functioning. Health-related and social time-varying factors were shown to partly but not wholly explain the observed associations.
Conclusion . Arts engagement amongst the population as a whole may help enhance positive mental health and life satisfaction, and protect against mental distress. These results are not explained by any time-constant confounding factors.