bluuebunny/crossref_metadata_2025_split huggingface dataset:
Jones Fractures Identified at the National Football League Scouting Combine: Assessment of Prognostic Factors, Computed Tomography Findings, and Initial Career Performance
Authors: Spang Robert C. , Haber Daniel B. , Beaulieu-Jones Brendin R. , Stupay Kristen L. , Sanchez George , Sanchez Anthony , Murphy Colin P. , Whalen James M. , Van Allen Joseph J. , Price Mark D. , Clanton Thomas O. , Provencher Matthew T. 
Published: August 2018

Background: Jones fractures result in subsequent dysfunction and remain an issue for athletes. Purpose: To (1) describe the epidemiology, treatment, and impact of Jones fractures identified at the National Football League (NFL) Scouting Combine on players’ early careers and (2) establish the value of computed tomography (CT) to determine bony healing after a fracture in prospective players. Study Design: Cohort study; Level of evidence, 3. Methods: All players who attended the combine between 2009 and 2015 were retrospectively reviewed to identify their history of Jones fractures. The playing position, treatment method, and number of missed collegiate games were recorded. The mean overall draft pick number, number of games started and played, snap percentage, and position-specific performance scores (fantasy score) over the first 2 years in the NFL were compared between players with fractures and controls. An imaging classification system was applied based on grading of each quadrant of the fifth metatarsal (plantar, dorsal, medial, lateral), with a score of 0 for not healed or 1 for healed. Results: Overall, the number of Jones fractures identified was 72 in 2285 athletes (3.2%), with all treated via intramedullary screw fixation. The mean overall draft pick number for players with fractures was 111.2 ± 67.9 compared with 99.0 ± 65.9 for controls ( P = .12). Performance scores for players with fractures were lower than those for controls across all positions, with a significant difference in running backs (2.6 vs 4.0, respectively; P < .001) and defensive linemen (1.4 vs 2.3, respectively; P = .02). The mean CT score was 2.5 ± 1.3. Of the 32 athletes who underwent imaging, 16 Jones fractures (50.0%) were healed or nearly healed, 12 (37.5%) were partially healed, and 4 (12.5%) showed little or no healing. The plantar cortex demonstrated the least healing (18/32; 56.3%), followed by the lateral cortex (15/32; 46.9%). Players with a mean score <1 were found to have fewer games started (2.7 ± 2.5) than those with 1 to 3 cortices healed (17.4 ± 10.4) or all cortices healed (8.7 ± 11.2). Conclusion: Based on CT, 50% of all players with a previous Jones fracture demonstrated incomplete healing. Moreover, position-specific performance scores over the first 2 years of a player’s career were lower across all positions for those with fractures compared with controls. Players with CT scores <1 were found to start fewer games and were drafted later than controls.
The Association Between Patient Satisfaction and Patient-Reported Health Outcomes
Authors: Chen Qinyu , Beal Eliza W , Okunrintemi Victor , Cerier Emily , Paredes Anghela , Sun Steven , Olsen Griffin , Pawlik Timothy M 
Published: August 2018

Objective: Although patient satisfaction is increasingly used to rate hospitals, it is unclear how patient satisfaction is associated with health outcomes. We sought to define the relationship of self-reported patient satisfaction and health outcomes. Design: Retrospective cross-sectional analysis using regression analyses and generalized linear modeling. Setting: Utilizing the Medical Expenditure Panel Survey Database (2010-2014), patients who had responses to survey questions related to satisfaction were identified. Participants: Among the 9166 patients, representing 106 million patients, satisfaction was rated as optimal (28.2%), average (61.1%), and poor (10.7%). Main Outcome Measures: We sought to define the relationship of self-reported patient satisfaction and health outcomes. Results: Patients who were younger, male, black/African American, with Medicaid insurance, as well as patients with lower socioeconomic status were more likely to report poor satisfaction (all P < .001). In the adjusted model, physical health score was not associated with an increased odds of poor satisfaction (1.42 95% confidence interval [CI]: 0.88-2.28); however, patients with a poor mental health score or ≥2 emergency department visits were more likely to report poor overall satisfaction (3.91, 95% CI: 2.34-6.5; 2.24, 95% CI: 1.48-3.38, respectively). Conclusion: Poor satisfaction was associated with certain unmodifiable patient-level characteristics, as well as mental health scores. These data suggest that patient satisfaction is a complex metric that can be affected by more than provider performance.
Myeloma escape after stem cell transplantation is a consequence of T-cell exhaustion and is prevented by TIGIT blockade
Authors: Minnie Simone A. , Kuns Rachel D. , Gartlan Kate H. , Zhang Ping , Wilkinson Andrew N. , Samson Luke , Guillerey Camille , Engwerda Christian , MacDonald Kelli P. A. , Smyth Mark J. , Markey Kate A. , Vuckovic Slavica , Hill Geoffrey R. 
Published: August 2018

Key Points
Myeloma promotes CD8+ T-cell exhaustion and IL-10 secretion from dendritic cells. PD-1 and TIGIT-targeted checkpoint inhibition is effective after SCT.
Biology and management of primary effusion lymphoma
Authors: Shimada Kazuyuki , Hayakawa Fumihiko , Kiyoi Hitoshi 
Published: August 2018

AbstractPrimary effusion lymphoma (PEL) is a rare B-cell malignancy that most often occurs in immunocompromised patients, such as HIV-infected individuals and patients receiving organ transplantation. The main characteristic of PEL is neoplastic effusions in body cavities without detectable tumor masses. The onset of the disease is associated with latent infection of human herpes virus 8/Kaposi sarcoma–associated herpes virus, and the normal counterpart of tumor cells is B cells with plasmablastic differentiation. A condition of immunodeficiency and a usual absence of CD20 expression lead to the expectation of the lack of efficacy of anti-CD20 monoclonal antibody; clinical outcomes of the disease remain extremely poor, with an overall survival at 1 year of ∼30%. Although recent progress in antiretroviral therapy has improved outcomes of HIV-infected patients, its benefit is still limited in patients with PEL. Furthermore, the usual high expression of programmed death ligand 1 in tumor cells, one of the most important immune-checkpoint molecules, results in the immune escape of tumor cells from the host immune defense, which could be the underlying mechanism of poor treatment efficacy. Molecular-targeted therapies for the activating pathways in PEL, including NF-κB, JAK/STAT, and phosphatidylinositol 3-kinase/AKT, have emerged to treat this intractable disease. A combination of immunological recovery from immune deficiency, overcoming the immune escape, and the development of more effective drugs will be vital for improving the outcomes of PEL patients in the future.
RETRACTED ARTICLE: SP1-induced lncRNA AGAP2-AS1 expression promotes chemoresistance of breast cancer by epigenetic regulation of MyD88
Authors: Dong Huaying , Wang Wei , Mo Shaowei , Chen Ru , Zou Kejian , Han Jing , Zhang Fan , Hu Jianguo 
Published: August 2018

AbstractBackgroundResistance to trastuzumab has become a leading cause of mortality in breast cancer patients and is one of the major obstacles for improving the clinical outcome. Cell behavior can be modulated by long non-coding RNAs (lncRNAs), but the contribution of lncRNAs in trastuzumab resistance to breast cancer is largely unknown. To this end, the involvement and regulatory function of lncRNA AGAP2-AS1 in human breast cancer are yet to be investigated.MethodsTrastuzumab-resistant SKBR-3 and BT474 cells were obtained by continuous culture with 5 mg/mL trastuzumab for 6 months. RT-qPCR assay was used to determine the expression of AGAP2-AS1 in tissues and cells. RNA fluorescence in situ hybridization was used to investigate the subcellular location of AGAP2-AS1 in breast cancer cells. Bioinformatic analysis, chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), western blotting, and immunofluorescence were carried out to verify the regulatory interaction of AGAP2-AS1, CREB-binding protein (CBP), and MyD88. In addition, a series of in vitro assays and a xenograft tumor model were used to analyze the functions of AGAP2-AS1 in breast cancer cells.ResultsAGAP2-AS1 was upregulated and transcriptionally induced by SP1 in breast cancer. Overexpression of AGAP2-AS1 promoted cell growth, suppressed apoptosis, and caused trastuzumab resistance, whereas knockdown of AGAP2-AS1 showed an opposite effect. MyD88 was identified as a downstream target of AGAP2-AS1 and mediated the AGAP2-AS1-induced oncogenic effects. Mechanistically, the RIP assay revealed that AGAP2-AS1 could bind to CBP, a transcriptional co-activator. ChIP assays showed that AGAP2-AS1-bound CBP increased the enrichment of H3K27ac at the promoter region of MyD88, thus resulting in the upregulation of MyD88. Gain- and loss-of-function assays confirmed that the NF-κB pathway was activated by MyD88 and AGAP2-AS1. Furthermore, high AGAP2-AS1 expression was associated with poor clinical response to trastuzumab therapy in breast cancer patients.ConclusionAGAP2-AS1 could promote breast cancer growth and trastuzumab resistance by activating the NF-κB signaling pathway and upregulating MyD88 expression. Therefore, AGAP2-AS1 may serve as a novel biomarker for prognosis and act as a therapeutic target for the trastuzumab treatment.
Palpable Breast Lump Triage by Minimally Trained Operators in Mexico Using Computer-Assisted Diagnosis and Low-Cost Ultrasound
Authors: Love Susan M. , Berg Wendie A. , Podilchuk Christine , López Aldrete Ana Lilia , Gaxiola Mascareño Aarón Patricio , Pathicherikollamparambil Krishnamohan , Sankarasubramanian Ananth , Eshraghi Leah , Mammone Richard 
Published: August 2018

Purpose In low- to middle-income countries (LMICs), most breast cancers present as palpable lumps; however, most palpable lumps are benign. We have developed artificial intelligence–based computer-assisted diagnosis (CADx) for an existing low-cost portable ultrasound system to triage which lumps need further evaluation and which are clearly benign. This pilot study was conducted to demonstrate that this approach can be successfully used by minimally trained health care workers in an LMIC country. Patients and Methods We recruited and trained three nonradiologist health care workers to participate in an institutional review board–approved, Health Insurance Portability and Accountability Act–compliant pilot study in Jalisco, Mexico, to determine whether they could use portable ultrasound (GE Vscan Dual Probe) to acquire images of palpable breast lumps of adequate quality for accurate computer analysis. Images from 32 women with 32 breast masses were then analyzed with a triage-CADx system, generating an output of benign or suspicious (biopsy recommended). Triage-CADx outputs were compared with radiologist readings. Results The nonradiologists were able to acquire adequate images. Triage by the CADx software was as accurate as assessment by specialist radiologists, with two (100%) of two cancers considered suspicious and 30 (100%) of 30 benign lesions classified as benign. Conclusion A portable ultrasound system with CADx software can be successfully used by first-level health care workers to triage palpable breast lumps. These results open up the possibility of implementing practical, cost-effective triage of palpable breast lumps, ensuring that scarce resources can be dedicated to suspicious lesions requiring further workup.
One month of hyperglycemia alters spectral responses of the zebrafish photopic electroretinogram
Authors: Tanvir Zaid , Nelson Ralph F. , DeCicco-Skinner Kathleen , Connaughton Victoria P. 
Published: August 2018

ABSTRACT
Prolonged hyperglycemia can alter retinal function, ultimately resulting in blindness. Adult zebrafish adults exposed to alternating conditions of 2% glucose/0% glucose display a 3× increase in blood sugar levels. After 4 weeks of treatment, electroretinograms (ERGs) were recorded from isolated, perfused, in vitro eyecups. Control animals were exposed to alternating 2% mannitol/0% mannitol (osmotic control) or to alternating water (0% glucose/0% glucose; handling control). Two types of ERGs were recorded: (1) native ERGs measured using white-light stimuli and medium without synaptic blockers; and (2) spectral ERGs measured with an AMPA/kainate receptor antagonist, isolating photoreceptor-to-ON-bipolar-cell synapses, and a spectral protocol that separated red (R), green (G), blue (B) and UV cone signals. Retinas were evaluated for changes in layer thickness and for the inflammatory markers GFAP and Nf-κB (RelA or p65). In native ERGs, hyperglycemic b- and d-waves were lower in amplitude than the b- and d-waves of mannitol controls. Alteration of waveshape became severe, with b-waves becoming more transient and ERG responses showing more PIII-like (a-wave) characteristics. For spectral ERGs, waveshape appeared similar in all treatment groups. However, a1- and b2-wave implicit times were significantly longer, and amplitudes were significantly reduced, in response to hyperglycemic treatment, owing to the functional reduction in signals from R, G and B cones. Nf-κB increased significantly in hyperglycemic retinas, but the increase in GFAP was not significant and retinal layer thickness was unaffected. Thus, prolonged hyperglycemia triggers an inflammatory response and functional deficits localized to specific cone types, indicating the rapid onset of neural complications in the zebrafish model of diabetic retinopathy.
Extraction of Urinary Metabolite-Derived Biomarker Candidate for Breast Cancer
Authors: Sakairi Minoru , Abe Mayumi , Tanaka Naoki 
Published: August 2018

Abstract
Urine is more than 90% water, and can contain more than 3000 metabolites. Consequently, extraction of biomarker candidates from urine for measuring subtle fluctuations in the quantities of metabolites in healthy individuals and cancer patients is very difficult. A variety of technologies, such as liquid chromatography/mass spectrometry (LC/MS), for analysis of urinary metabolites and identification of substances that show fluctuations in cancer patients compared with healthy individuals was used for this purpose. The substances detected by LC/MS were evaluated using machine learning, multivariate analysis to reduce and visualize parameters, and mass spectrometry for structural estimation of metabolites with unknown structures. One of the important biomarker candidates for breast cancer was determined to be 2-amino-4-methyl-1,1-pentanediol by an MS/MS spectrum. A one-dimensional linear discriminant analysis shows that this compound is estimated to be a promising biomarker for breast cancer. Urinary metabolites are found to be biomarkers for breast cancer.
Performance of the 4Kscore Test in Plasma and Serum and Stability of the Component Analytes in Clinical Samples
Authors: Higgins Christina E , Neybold Patricia , Holdridge Marcella B , Barnes Catherine R , Dong Yan , Reeve Michael , Mathur Vinita , Weisberger James , Linder Vincent 
Published: August 2018

Abstract

Background
The 4Kscore Test determines a personalized risk score for aggressive prostate cancer by combining the blood sample measurements of total prostate-specific antigen (tPSA), free PSA (fPSA), intact PSA (iPSA), and human kallikrein-related peptidase 2 (hK2) with patient clinical information to generate the patient risk's score; thus, accuracy and precision of the 4Kscore depend on the reliability of these measurements. Although tPSA and fPSA are measured on a Food and Drug Administration (FDA)-approved platform, the performance of the iPSA and hK2 assays in the clinical setting has not previously been reported.

Methods
Analytical performance was determined for the iPSA and hK2 assays in both serum and EDTA plasma, according to Clinical and Laboratory Standards Institute guidelines. Equivalence of the 4Kscore in both sample matrices was demonstrated in a 353-patient clinical cohort, and the stability of endogenous iPSA and hK2 for at least 3 days was demonstrated in a smaller subset.

Results
Intralaboratory and interlaboratory precision of the iPSA and hK2 assays in both matrices was comparable with that of FDA-approved tPSA and fPSA assays (&lt;18% for iPSA; &lt;8% for hK2). The picogram per milliliter sensitivity and wide dynamic range of the iPSA and hK2 assays allowed for accurate measurements in the target population. The 4Kscore generated in either matrix up to 3 days after collection is equivalent to that measured within 24 h of collection (Passing–Bablok slope 95% CI: plasma, 0.999–1.034; serum, 0.997–1.040).

Conclusions
The robust performance of component assays and reliable stability of the endogenous analytes in clinical samples proven here ensures an accurate 4Kscore Test result.
Elevated Serum Megakaryocyte Potentiating Factor as a Predictor of Poor Survival in Patients with Mesothelioma and Primary Lung Cancer
Authors: Yu Yunkai , Ryan Bríd M , Thomas Anish , Morrow Betsy , Zhang Jingli , Kang Zhigang , Zingone Adriana , Onda Masanori , Hassan Raffit , Pastan Ira , Cao Liang 
Published: August 2018

Abstract

Background
There is an urgent need for a companion assay to work with mesothelin-targeted therapeutic agents and for noninvasive and accurate prognostication of malignant mesothelioma (MM) patients. We report the development and validation of a blood-based assay for megakaryocyte potentiating factor (MPF) and the evaluation of its effectiveness for prognosis in MM and lung cancer patients.

Methods
Using electrochemiluminescence technology, we developed a sensitive MPF assay and performed both analytical and clinical validations. Further, the effectiveness of the MPF assay in predicting prognosis was evaluated for 95 MM and 272 lung cancer patients.

Results
We performed comprehensive analytical and clinical validation, including precision and accuracy, interference, preanalytical variables, sensitivity, and specificity for mesothelioma. In MM patients, increased serum MPF is a predictor of poor survival with a hazard ratio (HR) = 2.46 (log-rank P = 0.003; n = 95). In refractory MM patients, increased MPF is a strong predictor of poor outcome with an HR = 6.12 (log-rank P = 0.0007; n = 57). In a lung cancer patient cohort, increased MPF is a predictor of poor survival, with an HR = 1.57 (log-rank P = 0.003; n = 272).

Conclusions
The MPF assay has robust technical characteristics, with strong analytic and clinical validation. Clinical studies indicate that increased serum MPF is a predictor of poor survival for MM patients, throughout the course of the disease. Increased MPF is also associated with poor overall survival for patients with newly diagnosed lung cancer.
Reference Intervals Generated by Electronic Medical Record Data Mining with Clinical Exclusions: Age-Specific Intervals for Thyroid-Stimulating Hormone from 33038 Euthyroid Patients
Authors: Drees Julia C , Huang Karl , Petrie Matthew S , Lorey Thomas S , Dlott Richard S 
Published: August 2018

Abstract

Background
Serum thyroid-stimulating hormone (TSH) reference intervals are dependent on population characteristics, including prevalent thyroid disease and iodine status. Studies in the US have demonstrated increasing TSH levels with age, and the American Thyroid Association recommends higher TSH goals for older patients taking thyroid supplementation, but few laboratories offer age-specific reference intervals for TSH. Our objective was to establish TSH reference ranges in our racially diverse population in northern California.

Methods
Data mining of electronic medical records was used with the a posteriori approach to select a euthyroid reference population for TSH reference intervals. A report gathered all TSH results from 2 weeks from &gt;1 year in the past, excluding results from patients with thyroid-related disease or medication use at any time before or after the TSH test.

Results
The reference population numbered 33038 and consisted of approximately 44% of the total TSH results reported in the selected time periods. The population identified as 46.5% white, 18.3% Asian, 17.0% Hispanic/Latino, 8.0% black/African American, and 10.3% other or unknown. These data demonstrate an increase in the median and 97.5 percentile of TSH levels with increasing age in adults. No clinically significant difference was seen between female and male individuals or between the self-identified races, except for lower TSH levels in the black/African American population.

Conclusions
The a posteriori approach using data mining for disease-specific criteria proved to be an efficient method for obtaining a large healthy reference population. Age-specific TSH reference ranges could prevent inappropriate diagnoses of subclinical hypothyroidism in older patients.
Galactose-1-Phosphate Uridyltransferase Activities in Different Genotypes: A Retrospective Analysis of 927 Samples
Authors: Yuzyuk Tatiana , Wilson Andrew R , Mao Rong , Pasquali Marzia 
Published: August 2018

Abstract

Background
Classic galactosemia is an inherited disorder of galactose metabolism caused by the impaired activity of galactose-1-phosphate uridyltransferase (GALT). Untreated galactosemia is life-threatening; however, early dietary intervention prevents mortality and reduces morbidity associated with this disease. The diagnosis of galactosemia includes the measurement of GALT activity in red blood cells (RBC) and GALT gene analysis. In this study, we evaluate GALT activity in different genotypes using the results of combined biochemical and molecular testing in 927 samples.

Methods
GALT activity in RBC was measured by LC-MS/MS. The analysis of the GALT gene was performed by targeted gene analysis and/or full gene sequencing. Samples were assigned based on the presence of pathogenic (G) or Duarte 2 (D) variants, or their absence (Neg), to G/G, D/G, G/Neg, D/D, D/Neg, and Neg/Neg genotypes. Finite mixture models were applied to investigate distributions of GALT activities in these genotypes. The reference ranges were determined using the central 95% of values of GALT activities.

Results
The ranges of GALT activity in G/G, D/G, G/Neg, D/D, D/Neg, and Neg/Neg genotypes are 0.0 to 0.7 μmol·h−1 gHb−1, 3.1 to 7.8 μmol·h−1 gHb−1, 6.5 to 16.2 μmol·h−1 gHb−1, 6.4 to 16.5 μmol·h−1 gHb−1, 12.0 to 24.0 μmol·h−1 gHb−1, and 19.4 to 33.4 μmol·h−1 gHb−1, respectively.

Conclusions
The GALT activity ranges established in this study are in agreement with the expected impact of the genotype on the enzymatic activity. Molecular findings should be interpreted in view of biochemical results to confirm genotype–phenotype correlation.