bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characteristics and outcomes of late‐onset BK virus nephropathy in kidney and kidney‐pancreas transplant recipients
Authors: Imlay Hannah , Whitaker Kathryn , Fisher Cynthia E. , Limaye Ajit P. 
Published: May 2018

AbstractBackgroundBK virus nephropathy (BKPyVAN) is a major complication in kidney transplant recipients (KTR) and typically occurs within 1 year of transplant. Guidelines vary in recommendations for BKPyV screening beyond 1 year. A systematic characterization of risk factors and outcomes of late‐onset (>1 year) BKPyVAN has not previously been reported.MethodsWe retrospectively compared characteristics and outcomes of early‐ (<1 year) and late‐onset BKPyVAN (definitive [biopsy‐confirmed] or presumptive [plasma BKPyV >10 000 copies/mL]) in a cohort of 671 KTR and simultaneous kidney‐pancreas transplant (SPK) recipients between 2008 and 2013 at a single US transplant center. Proportions were compared using Chi‐square or Fisher's exact test with P < .05 considered significant.ResultsBKPyVAN was diagnosed in 96 (14.3%) patients (proven 16.7%, presumptive 83.3%): 79 (82.3%) early‐ and 17 (17.7%) late‐onset. The proportion with late‐onset BKPyVAN was significantly higher among SPK than KTR (4 of 7 [57.1%] vs 13 of 89 [14.6%], P = .017). Late‐onset represented “de novo” infection (no BKPyV detection within the first year) in 14 (82.4%) and progression of earlier lower grade BKPyV reactivation in 3 (17.6%). Clinical outcomes were similar for early‐ and late‐onset BKPyVAN (P > .05 all comparisons). In a pooled analysis of prior studies of BKPyVAN in SPK recipients, 62.9% (17 of 27) were late‐onset.ConclusionA significant proportion of BKPyVAN is late‐onset, especially among SPK recipients, and supports a longer duration of BKPyV monitoring for SPK recipients than recommended in some guidelines.
DisseminatedMycobacterium bovisinfection post‐kidney transplant following remote intravesicalBCGtherapy for bladder cancer
Authors: Ziegler Jennifer , Ho Julie , Gibson Ian W. , Nayak Jasmir G. , Stein Markus , Walkty Andrew , Orr Pamela 
Published: May 2018

AbstractIntravesical Bacillus Camlette‐Guérin (BCG) is the treatment of choice for non‐muscle invasive bladder cancer, and has been used successfully for over 40 years. A rare and potentially fatal complication of intravesicalBCGtherapy isBCG‐induced sepsis. We report a rare case in which a patient with end‐stage renal disease secondary to chronic granulomatous interstitial nephritis underwent remote, pre‐transplant intravesicalBCGtreatment for high‐grade non‐invasive papillary bladder carcinoma. The patient subsequently received a deceased donor kidney transplant 5 years afterBCGtherapy, with thymoglobulin induction therapy and standard triple maintenance immunosuppression. Two years post‐transplant, he developedBCG‐induced sepsis confirmed by cultures from urine, blood, and left native kidney biopsy. He died from disseminatedBCG‐induced sepsis and failure of his renal allograft. This case highlights the potential adverse reactions associated with intravesicalBCGtherapy that may occur years after bladder cancer therapy is completed, and should heighten physician awareness forBCG‐related infections during pre‐transplant assessment and post‐transplant care of solid organ transplants recipients.
Evaluating Performance During Maximum Effort Vertical Jump Landings
Authors: Harry John R. , Barker Leland A. , Eggleston Jeffrey D. , Dufek Janet S. 
Published: May 2018

The ability to rapidly complete a jump landing has received little attention in the literature despite the need for rapid performance in a number of sports. As such, our purpose was to investigate differences between groups of individuals who land quickly (FAST) and slowly (SLOW) relative to peak vertical ground reaction forces (vGRFs), loading rates, rates of vGRF attenuation, contributions to lower extremity mechanical energy absorption at the involved joints, and the onsets of preparatory joint flexion/dorsiflexion. Twenty-four healthy adults (26.1 [3.3] y, 75.7 [18.9] kg, 1.7 [0.1] m) were stratified into FAST and SLOW groups based on landing time across 8 jump-landing trials. Independent t tests (α = .05) and effect sizes (ESs; large ≥ 0.8) compared differences between groups. A greater rate of vGRF attenuation (P = .02; ES = 0.95) was detected in the FAST group. The FAST group also exhibited greater contributions to lower extremity energy absorption at the ankle (P = .03; ES = 0.98) and knee (P = .03; ES = 0.99) during loading and attenuation, respectively. The SLOW group exhibited greater contributions to energy absorption at the hip during loading (P = .02; ES = 1.10). Results suggest that individuals who land quickly utilize different energy absorption strategies than individuals who land slowly. Ultimately, the FAST group’s strategy resulted in superior landing performance (more rapid landing time).
Concurrent Validity of a Portable Force Plate Using Vertical Jump Force–Time Characteristics
Authors: Lake Jason , Mundy Peter , Comfort Paul , McMahon John J. , Suchomel Timothy J. , Carden Patrick 
Published: May 2018

This study examined concurrent validity of countermovement vertical jump reactive strength index modified and force–time characteristics recorded using a 1-dimensional portable and laboratory force plate system. Twenty-eight men performed bilateral countermovement vertical jumps on 2 portable force plates placed on top of 2 in-ground force plates, both recording vertical ground reaction force at 1000 Hz. Time to takeoff; jump height; reactive strength index modified; and braking and propulsion impulse, mean net force, and duration were calculated from the vertical force from both force plate systems. Results from both systems were highly correlated (r ≥ .99). There were small (d < 0.12) but significant differences between their respective braking impulse, braking mean net force, propulsion impulse, and propulsion mean net force (P < .001). However, limits of agreement yielded a mean value of 1.7% relative to the laboratory force plate system (95% confidence limits, 0.9%–2.5%), indicating very good agreement across all of the dependent variables. The largest limits of agreement were for jump height (2.1%), time to takeoff (3.4%), and reactive strength index modified (3.8%). The portable force plate system provides a valid method of obtaining reactive strength measures, and several underpinning force–time variables, from unloaded countermovement vertical jump. Thus, practitioners can use both force plates interchangeably.
Assessment of Knee Kinetic Symmetry Using Force Plate Technology
Authors: Nelson Aaron , Koslakiewicz Nathan , Almonroeder Thomas Gus 
Published: May 2018

Context: Athletes who have undergone an anterior cruciate ligament reconstruction often demonstrate more pronounced interlimb knee kinetic symmetry in comparison with uninjured athletes, even after they have completed rehabilitation. Part of the reason for the persistent asymmetry may be that sports medicine professionals are typically not able to assess knee joint kinetics within the clinic setting. Developing measures to assess knee joint kinetic symmetry could help to augment current rehabilitation practices. Objective: The purpose of this study was to explore the extent to which interlimb vertical ground reaction force (GRF) symmetry can predict knee kinetic symmetry during a drop landing task. Design: Cross-sectional study. Setting: Motion analysis laboratory. Participants: A total of 21 uninjured subjects (9 males and 12 females). Protocol: Three-dimensional kinematic data were collected using a multicamera system while subjects performed double-leg drop landings. GRF data were collected synchronously using 2 adjacent force plates. Main Outcome Measures: Knee joint moments and power were calculated for both limbs during the landing trials. An interlimb symmetry index (dominant/nondominant limb) was calculated for both the peak knee joint moment and power variables, as well as for the peak vertical GRFs. Linear regression analyses were performed to determine if the degree of symmetry in the peak vertical GRFs predicted the degree of symmetry for the kinetic variables. Results: The symmetry index for the vertical GRFs was a significant predictor of the symmetry indices for the knee joint moments (r = .81; P < .001) and power (r = .88; P < .001). Conclusion: Interlimb symmetry in the peak vertical GRFs can be used to predict knee joint kinetic symmetry during a double-leg drop landing task.
The Yin and Yang of SagS: Distinct Residues in the HmsP Domain of SagS Independently Regulate Biofilm Formation and Biofilm Drug Tolerance
Authors: Dingemans Jozef , Poudyal Bandita , Sondermann Holger , Sauer Karin 
Published: May 2018

The membrane-bound sensory protein SagS plays a pivotal role in
P. aeruginosa
biofilm formation and biofilm cells gaining their heightened resistance to antimicrobial agents, with SagS being the control point at which both pathways diverge. Here, we demonstrate for the first time that the two distinct pathways leading to biofilm formation and biofilm drug tolerance are under the control of two sets of amino acid residues located within the HmsP sensory domain of SagS. The respective amino acids are likely part of ligand binding interaction sites. Thus, our findings have the potential not only to enable the manipulation of SagS function but also to enable research of biofilm drug tolerance in a manner independent of biofilm formation (and vice versa). Moreover, the manipulation of SagS function represents a promising target/avenue open for biofilm control.
Outcomes of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) performed in eyes with failure of primary Descemet membrane endothelial keratoplasty (DMEK)
Authors: Graffi Shmuel , Leon Pia , Nahum Yoav , Gutfreund Shay , Spena Rossella , Mattioli Leila , Busin Massimo 
Published: May 2018

AimTo evaluate the outcomes of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) performed in eyes after failure of primary Descemet membrane endothelial keratoplasty (DMEK).MethodsThis was a retrospective, non-comparative interventional case series done in a tertiary care hospital. The study group included 21 eyes of patients which underwent UT-DSAEK following the failure of primary DMEK. Outcome measures included best spectacle-corrected visual acuity (BSCVA) and endothelial cell density (ECD) both recorded 6 and 12 months postoperatively as well as central graft thickness (CGT) measured 6 months after UT-DSAEK.ResultsWhen considering only eyes without comorbidities (17 of 21), 12 months after UT-DSAEK, BSCVA was ≥20/25 in 12/13 (92%) eyes and ≥20/20 in 4/13 (30%) eyes. Mean ECD loss rate was 38.9% at 12 months postoperatively (range 8%–57%). Six months postoperatively, CGT averaged at 81±34 µm (range 34–131 µm). No intraoperative complications were recorded. Postoperatively, one patient (no. 8) had graft wrinkles that were fixed 2 days following UT-DSAEK. Four patients have developed intraocular lens (IOL) opacification, and two of them underwent IOL exchange. No other postoperative complications were recorded.ConclusionsUT-DSAEK is instrumental in the management of primary DMEK graft failure, allowing visual rehabilitation which is comparable with that of repeat DMEK.
Declining trends of diabetic nephropathy, retinopathy and neuropathy with improving diabetes care indicators in Japanese patients with type 2 and type 1 diabetes (JDDM 46)
Authors: Yokoyama Hiroki , Araki Shin-ichi , Kawai Koichi , Yamazaki Katsuya , Tomonaga Osamu , Shirabe Shin-ichiro , Maegawa Hiroshi 
Published: May 2018

ObjectiveWe examined changes in prevalence of diabetic microvascular/macrovascular complications and diabetes care indicators for adults in Japan with type 2 and type 1 diabetes over one decade.Research design and methodsTwo independent cohorts were recruited with the same inclusion criteria in 2004 (cohort 1: 3319 with type 2 and 286 with type 1 diabetes) and in 2014 (cohort 2: 3932 with type 2 and 308 with type 1 diabetes). Prevalence of complications and care indicators including achieving treatment targets for glycemia, blood pressure, lipid control, body mass index (BMI), and smoking were compared. In addition, patients in cohort 1 were re-examined in 2014 and their data were compared with the baseline data of each cohort.ResultsIn type 2 diabetes, the prevalence of nephropathy, retinopathy, neuropathy, chronic kidney disease, current smoking and stroke significantly decreased, with improvements in achieving treatment target rates in cohort 2 two as compared with cohort 1. In type 1 diabetes, the prevalence of nephropathy, retinopathy, chronic kidney disease, and hemoglobin A1Cvalues significantly decreased. Decreases in prevalence of microvascular complications in type 2 diabetes were similarly found in each age-matched and sex-matched group, whereas younger patients exhibited marked increase in BMI and lower treatment target achieving rates compared with elderly patients. Regarding normoalbuminuric renal impairment, only a slight increase in the prevalence was observed both in type 2 and type 1 diabetes. In cohort 1, re-examined in 2014, care indicators were significantly improved from 2004, while complications increased with getting 10 years older.ConclusionsWe observed declining trends of diabetic microvascular complications with improvement in diabetes care indicators in type 2 and type 1 diabetes. Younger patients with type 2 diabetes exhibited marked increase in BMI and lower rates of achieving treatment targets compared with elderly patients, which remains a concern.
Characterizing and Predicting Users’ Behavior on Local Search Queries
Authors: Cacheda Fidel , Blanco Roi , Barbieri Nicola 
Published: May 2018

The use of queries to find products and services that are located nearby is increasing rapidly due mainly to the ubiquity of internet access and location services provided by smartphone devices. Local search engines help users by matching queries with a predefined geographical connotation (“local queries”) against a database of local business listings.
Local search differs from traditional Web search because, to correctly capture users’ click behavior, the estimation of relevance between query and candidate results must be integrated with geographical signals, such as distance. The intuition is that users prefer businesses that are physically closer to them or in a convenient area (e.g., close to their home). However, this notion of closeness depends upon other factors, like the business category, the quality of the service provided, the density of businesses in the area of interest, the hour of the day, or even the day of the week.

In this work, we perform an extensive analysis of online users’ interactions with a local search engine, investigating their intent, temporal patterns, and highlighting relationships between distance-to-business and other factors, such as business reputation, Furthermore, we investigate the problem of estimating the click-through rate on local search (
LCTR
) by exploiting the combination of standard retrieval methods with a rich collection of geo-, user-, and business-dependent features. We validate our approach on a large log collected from a real-world local search service. Our evaluation shows that the non-linear combination of business and user information, geo-local and textual relevance features leads to a significant improvements over existing alternative approaches based on a combination of relevance, distance, and business reputation [1].
Program Synthesis for Program Analysis
Authors: David Cristina , Kesseli Pascal , Kroening Daniel , Lewis Matt 
Published: May 2018

In this article, we propose a
unified
framework for designing static analysers based on
program synthesis
. For this purpose, we identify a fragment of second-order logic with restricted quantification that is expressive enough to model numerous static analysis problems (e.g., safety proving, bug finding, termination and non-termination proving, refactoring). As our focus is on programs that use bit-vectors, we build a decision procedure for this fragment over finite domains in the form of a program synthesiser. We provide instantiations of our framework for solving a diverse range of program verification tasks such as termination, non-termination, safety and bug finding, superoptimisation, and refactoring. Our experimental results show that our program synthesiser compares positively with specialised tools in each area as well as with general-purpose synthesisers.
Notch-Induced Myeloid Reprogramming in Spontaneous Pancreatic Ductal Adenocarcinoma by Dual Genetic Targeting
Authors: Cheung Phyllis F. , Neff Florian , Neander Christian , Bazarna Anna , Savvatakis Konstantinos , Liffers Sven-Thorsten , Althoff Kristina , Lee Chang-Lung , Moding Everett J. , Kirsch David G , Saur Dieter , Bazhin Alexandr V. , Trajkovic-Arsic Marija , Heikenwalder Mathias F. , Siveke Jens T. 
Published: May 2018

Abstract
Despite advances in our understanding of the genetics of pancreatic ductal adenocarcinoma (PDAC), the efficacy of therapeutic regimens targeting aberrant signaling pathways remains highly limited. Therapeutic strategies are greatly hampered by the extensive desmoplasia that comprises heterogeneous cell populations. Notch signaling is a contentious pathway exerting opposite roles in tumorigenesis depending on cellular context. Advanced model systems are needed to gain more insights into complex signaling in the multilayered tumor microenvironment. In this study, we employed a dual recombinase-based in vivo strategy to modulate Notch signaling specifically in myeloid cells to dissect the tumorigenic role of Notch in PDAC stroma. Pancreas-specific KrasG12D activation and loss of Tp53 was induced using a Pdx1-Flp transgene, whereas Notch signaling was genetically targeted using a myeloid-targeting Lyz2-Cre strain for either activation of Notch2-IC or deletion of Rbpj. Myeloid-specific Notch activation significantly decreased tumor infiltration by protumorigenic M2 macrophages in spontaneous endogenous PDAC, which translated into significant survival benefit. Further characterization revealed upregulated antigen presentation and cytotoxic T effector phenotype upon Notch-induced M2 reduction. This approach is the first proof of concept for genetic targeting and reprogramming of myeloid cells in a complex disease model of PDAC and provides evidence for a regulatory role of Notch signaling in intratumoral immune phenotypes.
Significance: This study provides insight into the role of myeloid-dependent NOTCH signaling in PDAC and accentuates the need to dissect differential roles of signaling pathways in different cellular components within the tumor microenvironment. Cancer Res; 78(17); 4997–5010. ©2018 AACR.
Detection of Gastric Cancer with Novel Methylated DNA Markers: Discovery, Tissue Validation, and Pilot Testing in Plasma
Authors: Anderson Bradley W. , Suh Yun-Suhk , Choi Boram , Lee Hyuk-Joon , Yab Tracy C. , Taylor William R. , Dukek Brian A. , Berger Calise K. , Cao Xiaoming , Foote Patrick H. , Devens Mary E. , Boardman Lisa A. , Kisiel John B. , Mahoney Douglas W. , Slettedahl Seth W. , Allawi Hatim T. , Lidgard Graham P. , Smyrk Thomas C. , Yang Han-Kwang , Ahlquist David A. 
Published: May 2018

AbstractPurpose: Gastric adenocarcinoma is the third most common cause of cancer mortality worldwide. Accurate and affordable noninvasive detection methods have potential value for screening and surveillance. Herein, we identify novel methylated DNA markers (MDM) for gastric adenocarcinoma, validate their discrimination for gastric adenocarcinoma in tissues from geographically separate cohorts, explore marker acquisition through the oncogenic cascade, and describe distributions of candidate MDMs in plasma from gastric adenocarcinoma cases and normal controls.Experimental Design: Following discovery by unbiased whole-methylome sequencing, candidate MDMs were validated by blinded methylation-specific PCR in archival case–control tissues from U.S. and South Korean patients. Top MDMs were then assayed by an analytically sensitive method (quantitative real-time allele-specific target and signal amplification) in a blinded pilot study on archival plasma from gastric adenocarcinoma cases and normal controls.Results: Whole-methylome discovery yielded novel and highly discriminant candidate MDMs. In tissue, a panel of candidate MDMs detected gastric adenocarcinoma in 92% to 100% of U.S. and South Korean cohorts at 100% specificity. Levels of most MDMs increased progressively from normal mucosa through metaplasia, adenoma, and gastric adenocarcinoma with variation in points of greatest marker acquisition. In plasma, a 3-marker panel (ELMO1, ZNF569, C13orf18) detected 86% (95% CI, 71–95) of gastric adenocarcinomas at 95% specificity.Conclusions: Novel MDMs appear to accurately discriminate gastric adenocarcinoma from normal controls in both tissue and plasma. The point of aberrant methylation during oncogenesis varies by MDM, which may have relevance to marker selection in clinical applications. Further exploration of these MDMs for gastric adenocarcinoma screening and surveillance is warranted. Clin Cancer Res; 24(22); 5724–34. ©2018 AACR.
Phase Ib Study of Binimetinib with Paclitaxel in Patients with Platinum-Resistant Ovarian Cancer: Final Results, Potential Biomarkers, and Extreme Responders
Authors: Grisham Rachel N. , Moore Kathleen N. , Gordon Michael S. , Harb Wael , Cody Gwendolyn , Halpenny Darragh F. , Makker Vicky , Aghajanian Carol A. 
Published: May 2018

Abstract
Purpose: Epithelial ovarian cancer (EOC) is a molecularly diverse disease. MEK inhibition targets tumors harboring MAPK pathway alterations and enhances paclitaxel-induced apoptosis in EOC. This phase Ib study evaluated the MEK inhibitor binimetinib combined with paclitaxel in patients with platinum-resistant EOC.
Patients and Methods: Patients received intravenous weekly paclitaxel with oral binimetinib in three different administration schedules. Outcomes were assessed by RECIST and CGIC CA-125 response criteria. Tumor samples were analyzed using next-generation sequencing.
Results: Thirty-four patients received ≥1 binimetinib dose. A 30-mg twice-a-day continuous or 45-mg twice-a-day intermittent binimetinib dose was deemed the recommended phase II dose (RP2D) in combination with 80 mg/m2 i.v. weekly paclitaxel. Rate of grade 3/4 adverse events was 65%. The best overall response rate was 18%—one complete (CR) and four partial responses (PR)—among 28 patients with RECIST-measurable disease. Eleven patients achieved stable disease (SD), yielding a clinical benefit rate (CR+PR+SD) of 57%. Response rates, per both RECIST and CA-125 criteria, were highest in the 45-mg twice-a-day continuous cohort and lowest in the 45-mg twice-a-day intermittent cohort. All four evaluable patients with MAPK pathway–altered tumors experienced clinical benefit.
Conclusions: The combination of binimetinib and intravenous weekly paclitaxel was tolerable in this patient population. The RP2D of binimetinib in combination with paclitaxel was 30 mg twice a day as a continuous or 45 mg twice a day as an intermittent dose. Although response rates were modest, a higher clinical benefit rate was seen in patients harboring alterations affecting the MAPK pathway. Clin Cancer Res; 24(22); 5525–33. ©2018 AACR.