bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of corneal biomechanical properties in predicting of speed of myopic progression in children wearing orthokeratology lenses or single-vision spectacles
Authors: Wan Kin , Cheung Sin Wan , Wolffsohn James S , Orr Janis B , Cho Pauline 
Published: December 2018

ObjectiveTo determine the characteristics of children who were likely to progress rapidly and gain the greatest benefit from orthokeratology (ortho-k) treatment.Methods and analysisThe files of 113 children who participated in two myopia control studies and wore either ortho-k lenses (n=62) or single-vision spectacles (SVS) (n=51) were reviewed. Baseline cycloplegic subjective refraction, central corneal thickness, axial length, keratometry, intraocular pressure, corneal biomechanical properties and 24-month axial length data were retrieved and analysed.ResultsMultivariate analysis showed that there was significant negative correlation between axial elongation and baseline age and corneal hysteresis (p<0.05) in the SVS group. In the ortho-k group, only baseline age was significantly and negatively associated with axial elongation (p<0.01).ConclusionCorneal biomechanical properties and baseline age can predict the rate of axial elongation in myopic children. It may be beneficial for younger myopic children with low corneal hysteresis to commence ortho-k treatment as early as possible.
Epidemiology of sports injuries in basketball: integrative systematic review
Authors: Andreoli Carlos Vicente , Chiaramonti Bárbara Camargo , Biruel Elisabeth , Pochini Alberto de Castro , Ejnisman Benno , Cohen Moises 
Published: December 2018

IntroductionBasketball is a contact sport with complex movements that include jumps, turns and changes in direction, which cause frequent musculoskeletal injuries in all regions of the body.ObjectiveThis is an integrative systematic review of the epidemiology of musculoskeletal injuries in basketball.MethodsThis is an integrative review based on the following sources of information: PubMed/MEDLINE, Embase, LILACS, BBO-Biblioteca Brasileira de Odontologia, IBECS-Índice Bibliográfico Espanhol em Ciências da Saúde, nursing journals, dental journals and core clinical journals in the last 10 years with studies addressing the general epidemiology of sports injuries in basketball.ResultsIn total, 268 articles were selected, of which 11 were eligible for the integrative review. A total of 12 960 injuries were observed, most of which occurred in the lower limbs (63.7%), with 2832 (21.9%) ankle injuries and 2305 (17.8%) knee injuries. Injuries in the upper limbs represented 12%–14% of the total injuries. Children and adolescents received head injuries more often compared with the other age and skill categories. In the adult category, there was an increased prevalence of injuries in the trunk and spine. In the upper limbs, hands, fingers and wrists were affected more frequently than the shoulders, arms and forearms. In the masters’ category, there was an increase in the incidence of thigh injuries.ConclusionThe lower limbs were the most affected, with the ankle and knee joints having the highest prevalence of injuries regardless of gender and category. Further randomised studies, increased surveillance and epidemiological data collection are necessary to improve knowledge on sports injuries in basketball and to validate the effectiveness of preventive interventions.
Double-beta decay and its potential to explore beyond standard model physics
Authors: Stoica Sabin 
Published: December 2018

Double-beta decay (DBD) is a rare nuclear process of great interest due to its potential to provide information about physics beyond the Standard Model (BSM). For example, the discovery of the neutrinoless double-beta [Formula: see text] decay mode could give information about important issues such as possible violations of Lorentz symmetry and lepton number, nature of neutrinos (are they Dirac- or Majorana-like particles?), neutrino absolute masses, neutrino mass hierarchy, existence of heavy (sterile) neutrinos, etc. In the theoretical study of DBD, one needs a precise calculation of the nuclear matrix elements (NMEs) and phase space factors (PSFs) entering the half-lives formulas, for different decay modes, transitions and mechanisms of occurrence. Reliable computations of these quantities may result in reliable predictions of DBD half-lives and constrains of the BSM parameters related to the possible mechanisms that can contribute to the [Formula: see text] decay. In this paper, I briefly review the theoretical challenges in the study of [Formula: see text] decay. I describe the computation of the NMEs and PSFs and present results for a number of selected nuclei. Then, I show the broader potential of this process to provide information about BSM physics and present new upper limits for parameters associated with light neutrino, heavy neutrino and SUSY exchange mechanisms. Finally, I suggest a more consistent approach to calculate the NMEs and PSFs, namely to compute directly their product and discuss some possibilities to reduce the errors related to the uncertain value of the axial-vector constant.
Covariant information theory and emergent gravity
Authors: Vanchurin Vitaly 
Published: December 2018

Informational dependence between statistical or quantum subsystems can be described with Fisher information matrix or Fubini-Study metric obtained from variations/shifts of the sample/configuration space coordinates. Using these (noncovariant) objects as macroscopic constraints, we consider statistical ensembles over the space of classical probability distributions (i.e. in statistical space) or quantum wave functions (i.e. in Hilbert space). The ensembles are covariantized using dual field theories with either complex scalar field (identified with complex wave functions) or real scalar field (identified with square roots of probabilities). We construct space–time ensembles for which an approximate Schrodinger dynamics is satisfied by the dual field (which we call infoton due to its informational origin) and argue that a full space–time covariance on the field theory side is dual to local computations on the information theory side. We define a fully covariant information-computation tensor and show that it must satisfy certain conservation equations. Then we switch to a thermodynamic description of the quantum/statistical systems and argue that the (inverse of) space–time metric tensor is a conjugate thermodynamic variable to the ensemble-averaged information-computation tensor. In (local) equilibrium, the entropy production vanishes, and the metric is not dynamical, but away from the equilibrium the entropy production gives rise to an emergent dynamics of the metric. This dynamics can be described approximately by expanding the entropy production into products of generalized forces (derivatives of metric) and conjugate fluxes. Near equilibrium, these fluxes are given by an Onsager tensor contracted with generalized forces and on the grounds of time-reversal symmetry, the Onsager tensor is expected to be symmetric. We show that a particularly simple and highly symmetric form of the Onsager tensor gives rise to the Einstein–Hilbert term. This proves that general relativity is equivalent to a theory of nonequilibrium (thermo)dynamics of the metric, but the theory is expected to break down far away from equilibrium where the symmetries of the Onsager tensor are to be broken.
The Role of Entrepreneurial Coaching in the Restarting Process After Business Failure
Authors: Anis Ben Salem , Lassaad Lakhal , Mbarek Rahmoun , Carrera-Jiménez Javier A. 
Published: December 2018

The aim of this paper is to identify the adequate entrepreneurial support elements for business restarting after business failure. An exploratory study was conducted with fifteen SMEs within the interpretivist paradigm. The study reveals a matrix of factors that make for adequate entrepreneurial support to assist restarting business. In addition, this study shows that psychological coaching is an efficient remedy to reduce emotional shock after experiencing unplanned failure whereas social coaching is an efficient support of integrating successor following a planned failure in some social network. However, current thinking on incubation should be increased in order to help with business recovery especially as there is a high failure rate associated with startups. This research attempts to ensure a possible relationship between entrepreneurial support practices and failing entrepreneurs’ needs.
ZEO, Inc.: Is the Market Ready for Wearables?
Authors: Marty Martin Wm. , Welsch Harold 
Published: December 2018

Zeo, Inc. was one of the pioneer companies in the quantified self-industry offering a digital solution for individuals suffering from sleep problems. The company was founded by three undergraduate students who successfully raised capital, make strategic partnerships with major brands like the National Football League (NFL), and introduced their products in stores like Best Buy.The collegiate founders recognized their lack of knowledge and skills from the beginning. To address this gap, they developed an advisory board to guide them on scientific matters. Later, they hired a seasoned executive with industry experience to run and grow the company. Zeo, Inc. also was getting favorable attention among leading sleep experts with publications in scientific journals about the promise of this innovative technology. Zeo, Inc. was positioned to potentially disrupt the technological and business model of the sleep industry at the time.Suddenly, Zeo, Inc. announced it was shutting down the company. Technology pundits, the media and customers were surprised, “Why would a fast-rising company shut down?” Given the lack of board and senior leadership transparency, many speculated as to why Zeo, Inc. closed. The reasons ranged from a lack of a focus on the business model to not keeping up with new entrants into the digital health space such as FitBit. This case highlights for students the growth stages of startups with an emphasis of how a widely acclaimed startup can fail and the lessons to be learned from failure.
Activation of Estrogen Receptor Alpha by Decitabine Inhibits Osteosarcoma Growth and Metastasis
Authors: Lillo Osuna Maria Angeles , Garcia-Lopez Jesus , El Ayachi Ikbale , Fatima Iram , Khalid Aysha B. , Kumpati Jerusha , Slayden Alexandria V. , Seagroves Tiffany N. , Miranda-Carboni Gustavo A. , Krum Susan A. 
Published: December 2018

Abstract

Osteosarcoma is a malignant tumor in the bone, which originates from normal osteoblasts or osteoblast precursors. Normal osteoblasts express estrogen receptor alpha (ERα); however, osteosarcomas do not express ERα due to promoter DNA methylation. Here we show that treatment of 143B osteosarcoma cells with decitabine (DAC, 5-Aza-2′-deoxycytidine) induces expression of ERα and leads to decreased proliferation and concurrent induction of osteoblast differentiation. DAC exposure reduced protein expression of metastasis-associated markers VIMENTIN, SLUG, ZEB1, and MMP9, with a concurrent decrease in mRNA expression of known stem cell markers SOX2, OCT4, and NANOG. Treatment with 17β-estradiol (E2) synergized with DAC to reduce proliferation. Overexpression of ERα inhibited proliferation and induced osteoblast differentiation, whereas knockout of ERα by CRISPR/Cas9 prevented the effects of DAC. In an orthotopic model of osteosarcoma, DAC inhibited tumor growth and metastasis of 143B cells injected into the tibia of NOD SCID gamma mice. Furthermore, ERα overexpression reduced tumor growth and metastasis, and ERα knockout prevented the effects of DAC in vivo. Together, these experiments provide preclinical evidence that the FDA-approved DNA methylation inhibitor DAC may be repurposed to treat patients with osteosarcoma based on its efficacy to decrease proliferation, to induce osteoblast differentiation, and to reduce metastasis to visceral organs.

Significance: These findings describe the effects of DNA methyltransferase inhibition on ERα and its potential role as a tumor suppressor in osteosarcoma.
See related commentary by Roberts, p. 1034
See related article by El Ayachi and colleagues; Cancer Res 79(5);982–93.
Urinary Cytokine Profile to Predict Response to Intravesical BCG with or without HS-410 Therapy in Patients with Non–muscle-invasive Bladder Cancer
Authors: Salmasi Amirali , Elashoff David A. , Guo Rong , Upfill-Brown Alexander , Rosser Charles J. , Rose Jason M. , Giffin Louise C. , Gonzalez Louis E. , Chamie Karim 
Published: December 2018

AbstractBackground:Despite extensive research to identify biomarkers of response in patients with non–muscle-invasive bladder cancer (NMIBC), there is no biomarker to date that can serve this purpose. Herein, we report how we leveraged serial urine samples to query a panel of cytokines at varying time points in an attempt to identify predictive biomarkers of response in NMIBC.Methods:Serial urine samples were collected from 50 patients with intermediate- or high-risk NMIBC enrolled in a phase II study, evaluating intravesical BCG ± intradermal HS-410 therapy. Samples were collected at baseline, week 7, week 13, week 28, and at end of treatment. A total of 105 cytokines were analyzed in each sample. To predict outcome of time-to-event (recurrence or progression), univariate and multivariable Cox analyses were performed.Results:Fifteen patients developed recurrence and 4 patients progressed during the follow-up period. Among clinicopathologic variables, ever-smoker versus nonsmoker status was associated with an improved response rate (HR 0.38; 95% confidence interval (CI), 0.14–0.99; P = 0.04). In the most clinically relevant model, the percent change (for 100 units) of IL18-binding protein-a (HR 1.995; 95% CI, 1.16–3.44; P = 0.01), IL23 (HR 1.12; 95% CI, 1.01–1.23; P = 0.03), IL8 (HR 0.27; 95% CI, 0.07–1.08; P = 0.06), and IFNγ-induced protein-10 (HR 0.95; 95% CI, 0.91–0.99; P = 0.04) at week 13 from baseline best predicted time to event.Conclusions:Urinary cytokines provided additional value to clinicopathologic features to predict response to immune-modulating agents in patients with NMIBC.Impact:This study serves as a hypothesis-generating report for future studies to evaluate the role of urine cytokines as a predictive biomarker of response to immune treatments.
Mutational Analysis of 472 Urothelial Carcinoma Across Grades and Anatomic Sites
Authors: Nassar Amin H. , Umeton Renato , Kim Jaegil , Lundgren Kevin , Harshman Lauren , Van Allen Eliezer M. , Preston Mark , Dong Fei , Bellmunt Joaquim , Mouw Kent W. , Choueiri Toni K. , Sonpavde Guru , Kwiatkowski David J. 
Published: December 2018

Abstract

Purpose:
The purpose of this study is to characterize the mutational landscape across the spectrum of urothelial carcinoma (UC) to identify mutational features and potential therapeutic targets.

Experimental Design:
Using targeted exome sequencing (n = 237 genes), we analyzed the mutation spectra of 82 low-grade nonmuscle-invasive bladder cancers (LG-NMIBC), 126 high-grade (HG) NMIBC, 199 muscle-invasive bladder cancers (MIBC), 10 LG-upper tract urothelial cancers (LG-UTUC), and 55 HG-UTUC.

Results:
FGFR3 and KDM6A mutations were significantly more common in LG-NMIBC (72% and 44%, respectively) versus other bladder subtypes. FGFR3 alterations were also enriched in LG-UTUC versus HG-UTUC tumors (80% vs. 16%). In contrast, TP53 and RB1 mutations were significantly more frequent in all 3 HG urothelial carcinoma subtypes than in LG-NIMBC (45%–58% vs. 4%; 9%–22% vs. 0; respectively). Among LG-NMIBC tumors, KDM6A mutations were more common in women than in men (71% vs. 38%). HG-NMIBC and MIBC had higher tumor mutational burden (TMB) than LG-NMIBC (P = 0.001 and P &lt; 0.01, respectively). DNA-damage repair (DDR) alterations were associated with a higher TMB in HG-NMIBC and MIBC tumors, and these two tumor types were also enriched for an APOBEC mutational signature compared with LG-NMIBC and HG-UTUC. Alterations in FGFR3, PIK3CA, and EP300 correlated with worse overall survival in HG-UTUC and occurred concurrently.

Conclusions:
Our analysis suggests that a fraction of MIBCs likely arise from precursor lesions other than LG-NMIBC. KDM6A mutations are twice as common in women with LG-NIMBC than those in men. DDR gene mutations and APOBEC mutagenesis drive mutations in HG-NMIBC and MIBC. UTUC has a distinct mutation profile from bladder cancer.
One-Year Outcomes After MitraClip for Functional Mitral Regurgitation
Authors: Ailawadi Gorav , Lim D. Scott , Mack Michael J. , Trento Alfredo , Kar Saibal , Grayburn Paul A. , Glower Donald D. , Wang Andrew , Foster Elyse , Qasim Atif , Weissman Neil J. , Ellis Jeffrey , Crosson Lori , Fan Frank , Kron Irving L. , Pearson Paul J. , Feldman Ted ,   On behalf of the EVEREST II Investigators
Published: December 2018

Background:
Secondary mitral regurgitation (SMR) occurs in the absence of organic mitral valve disease and may develop as the left ventricle dilates or remodels or as a result of leaflet tethering with impaired coaptation, most commonly from apical and lateral distraction of the subvalvular apparatus, with late annular dilatation. The optimal therapy for SMR is unclear. This study sought to evaluate the 1-year adjudicated outcomes of all patients with SMR undergoing the MitraClip procedure in the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) Investigational Device Exemption program, which is comprised of the randomized clinical trial, the prospective High-Risk Registry, and the REALISM Continued Access Registry (Multicenter Study of the MitraClip System).

Methods:
Patients with 3+/4+ SMR enrolled in EVEREST II were stratified by non-high surgical risk (non-HR) and high surgical risk (HR) status (defined as Society of Thoracic Surgeons risk of mortality ≥12% or predefined risk factors). Clinical, echocardiographic, and functional outcomes at 1 year were evaluated.

Results:

A total of 616 patients (482 HR, 134 non-HR; mean age, 73.3±10.5 years; Society of Thoracic Surgeons risk, 10.2±6.9%) with SMR underwent the MitraClip procedure. At baseline, 80.5% of patients were in New York Heart Association class III/IV. Major adverse events at 30 days included death (3.6%), stroke (2.3%), and renal failure (1.5%). At discharge, 88.8% had MR ≤2+. At 1 year, there were 139 deaths, and the Kaplan-Meier estimate of freedom from mortality was 76.8%. The majority of surviving patients (84.7%) remained with MR ≤2+ and New York Heart Association class I/II (83.0%). Kaplan-Meier survival at 1 year was 74.1% in HR patients and 86.4% in non-HR patients (
P
=0.0175). At 1 year, both groups achieved comparable MR reduction (MR ≤2+, 84.0% versus 87.0%) and improvement in left ventricular end-diastolic volume (−8.0 mL versus −12.7 mL), whereas New York Heart Association class I/II was found in 80.1% versus 91.8% (
P
=0.008) of HR and non-HR patients, respectively. In HR patients, the annualized rate of heart failure hospitalizations decreased from 0.68 to 0.46 in the 12 months before to 12 months after the procedure (
P
<0.0001).

Conclusions:
Transcatheter mitral valve repair with the MitraClip in patients with secondary MR is associated with acceptable safety, reduction of MR severity, symptom improvement, and positive ventricular remodeling.

Clinical Trial Registration:

https://www.clinicaltrials.gov
. Unique identifiers: NCT00209274, NCT01940120, and NCT01931956.
Uremic Toxin Indoxyl Sulfate Promotes Proinflammatory Macrophage Activation Via the Interplay of OATP2B1 and Dll4-Notch Signaling
Authors: Nakano Toshiaki , Katsuki Shunsuke , Chen Mingxian , Decano Julius L. , Halu Arda , Lee Lang Ho , Pestana Diego V. S. , Kum Angelo S. T. , Kuromoto Rodrigo K. , Golden Whitney S. , Boff Mario S. , Guimaraes Gabriel C. , Higashi Hideyuki , Kauffman Kevin J. , Maejima Takashi , Suzuki Takehiro , Iwata Hiroshi , Barabási Albert-László , Aster Jon C. , Anderson Daniel G. , Sharma Amitabh , Singh Sasha A. , Aikawa Elena , Aikawa Masanori 
Published: December 2018

Background:
Chronic kidney disease (CKD) increases cardiovascular risk. Underlying mechanisms, however, remain obscure. The uremic toxin indoxyl sulfate is an independent cardiovascular risk factor in CKD. We explored the potential impact of indoxyl sulfate on proinflammatory activation of macrophages and its underlying mechanisms.

Methods:
We examined in vitro the effects of clinically relevant concentrations of indoxyl sulfate on proinflammatory responses of macrophages and the roles of organic anion transporters and organic anion transporting polypeptides (OATPs). A systems approach, involving unbiased global proteomics, bioinformatics, and network analysis, then explored potential key pathways. To address the role of Delta-like 4 (Dll4) in indoxyl sulfate–induced macrophage activation and atherogenesis in CKD in vivo, we used 5/6 nephrectomy and Dll4 antibody in low-density lipoprotein receptor–deficient (Ldlr-/-) mice. To further determine the relative contribution of OATP2B1 or Dll4 to proinflammatory activation of macrophages and atherogenesis in vivo, we used siRNA delivered by macrophage-targeted lipid nanoparticles in mice.

Results:
We found that indoxyl sulfate–induced proinflammatory macrophage activation is mediated by its uptake through transporters, including OATP2B1, encoded by the SLCO2B1 gene. The global proteomics identified potential mechanisms, including Notch signaling and the ubiquitin-proteasome pathway, that mediate indoxyl sulfate-triggered proinflammatory macrophage activation. We chose the Notch pathway as an example of key candidates for validation of our target discovery platform and for further mechanistic studies. As predicted computationally, indoxyl sulfate triggered Notch signaling, which was preceded by the rapid induction of Dll4 protein. Dll4 induction may result from inhibition of the ubiquitin-proteasome pathway, via the deubiquitinating enzyme USP5. In mice, macrophage-targeted OATP2B1/Slco2b1 silencing and Dll4 antibody inhibited proinflammatory activation of peritoneal macrophages induced by indoxyl sulfate. In low-density lipoprotein receptor–deficient mice, Dll4 antibody abolished atherosclerotic lesion development accelerated in Ldlr-/- mice. Moreover, coadministration of indoxyl sulfate and OATP2B1/Slco2b1 or Dll4 siRNA encapsulated in macrophage-targeted lipid nanoparticles in Ldlr-/- mice suppressed lesion development.

Conclusions:
These results suggest that novel crosstalk between OATP2B1 and Dll4-Notch signaling in macrophages mediates indoxyl sulfate–induced vascular inflammation in CKD.