bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter Analysis of Transport Destinations for Pediatric Prehospital Patients
Authors: Lerner E. Brooke , Studnek Jonathan R. , Fumo Nicole , Banerjee Anjishnu , Arapi Igli , Browne Lorin R. , Ostermayer Daniel G. , Reynolds Stacy , Shah Manish I. 
Published: October 2018

AbstractBackgroundAlthough all emergency departments (EDs) should be ready to treat children, some may have illnesses or injuries that require higher‐level pediatric resources that are not available at all hospitals. There are no national guidelines for emergency medical services (EMS) providers about when to directly transport children to hospitals with higher‐level pediatric resources, with the exception of severe trauma. Variability exists in EMS protocols about when children warrant transport to hospitals with higher‐level pediatric care.ObjectiveThe objective was to determine how frequently pediatric patients are transported by EMS to hospitals with higher‐level pediatric resources and to evaluate distribution patterns based on illness and injury severity.MethodsWe conducted a retrospective analysis of all pediatric (age 0–18 years) transports in three large EMS systems between November 2014 and November 2016. Each community had a hospital with higher‐level pediatric resources that was within a 30‐minute transport time from any location. Patients were included if they were transported by ground ambulance and the request originated in the 9‐1‐1 system. We assessed the frequency of transports to a hospital with higher‐level pediatric resources. Data were stratified by chief complaint of illness or injury and severity. Potential risk for severe injury was defined as meeting the physiologic step of the field triage guidelines and potential risk for severe illness was defined as having an abnormal vital sign after adjusting for patient age.ResultsA total of 41,345 pediatric patients were transported by a participating EMS agency to an ED and had complete destination data. A total of 55% of all EMS‐transported pediatric patients were transported to a hospital with higher‐level pediatric resources. There was variation by site (range = 45%–71%) in the percentage of children who went to a hospital with higher‐level pediatric resources. Patients over 15 years of age went to general EDs (57%) more often than younger patients. When stratified by severity, 60% of those with potentially severe illness and 74% of those with potentially severe trauma were transported to a hospital with higher‐level pediatric resources.ConclusionsEMS providers commonly transport children to hospitals with higher‐level pediatric resources. However, more than one‐quarter of children with potentially severe injuries and illnesses are transported to general EDs.
Dual inhibition of enhancer of zeste homolog 1/2 overactivates WNT signaling to deplete cancer stem cells in multiple myeloma
Authors: Nakagawa Makoto , Fujita Shuhei , Katsumoto Takuo , Yamagata Kazutsune , Ogawara Yoko , Hattori Ayuna , Kagiyama Yuki , Honma Daisuke , Araki Kazushi , Inoue Tatsuya , Kato Ayako , Inaki Koichiro , Wada Chisa , Ono Yoshimasa , Yamamoto Masahide , Miura Osamu , Nakashima Yasuharu , Kitabayashi Issay 
Published: October 2018

Multiple myeloma (MM) is an incurable hematological malignancy caused by accumulation of abnormal clonal plasma cells. Despite the recent development of novel therapies, relapse of MM eventually occurs as a result of a remaining population of drug‐resistant myeloma stem cells. Side population (SP) cells show cancer stem cell‐like characteristics in MM; thus, targeting these cells is a promising strategy to completely cure this malignancy. Herein, we showed that SP cells expressed higher levels of enhancer of zeste homolog (EZH) 1 and EZH2, which encode the catalytic subunits of Polycomb repressive complex 2 (PRC2), than non‐SP cells, suggesting that EZH1 as well as EZH2 contributes to the stemness maintenance of the MM cells and that targeting both EZH1/2 is potentially a significant therapeutic approach for eradicating myeloma stem cells. A novel orally bioavailable EZH1/2 dual inhibitor, OR‐S1, effectively eradicated SP cells and had a greater antitumor effect than a selective EZH2 inhibitor in vitro and in vivo, including a unique patient‐derived xenograft model. Moreover, long‐term continuous dosing of OR‐S1 completely cured mice bearing orthotopic xenografts. Additionally, PRC2 directly regulated WNT signaling in MM, and overactivation of this signaling induced by dual inhibition of EZH1/2 eradicated myeloma stem cells and negatively affected tumorigenesis, suggesting that repression of WNT signaling by PRC2 plays an important role in stemness maintenance of MM cells. Our results show the role of EZH1/2 in the maintenance of myeloma stem cells and provide a preclinical rationale for therapeutic application of OR‐S1, leading to significant advances in the treatment of MM.
Vitamin D deficiency is associated with inferior survival of patients with extranodal natural killer/T‐cell lymphoma
Authors: Kim Seok Jin , Shu Cheng , Ryu Kyung Ju , Kang Danbee , Cho Juhee , Ko Young Hyeh , Lee Soo‐Youn , Guallar Eliseo , Zhao Weili , Kim Won Seog 
Published: October 2018

Vitamin D deficiency is a common health issue; however, the effect of vitamin D deficiency on the survival of T‐cell lymphoma is still not clear. We evaluated the impact of serum vitamin D level of patients with peripheral T‐cell lymphoma (PTCL) and extranodal natural killer/T‐cell lymphoma (ENKTL) on survival outcome. Pretreatment levels of 25‐hydroxyvitamin D [25(OH)D] and inflammatory cytokines were measured in serum samples that were archived at diagnosis, and we evaluated their association with survival in newly diagnosed patients with PTCL (n = 137) and ENKTL (n = 114) at a university‐based hospital in Korea. An independent cohort from Rui Jin Hospital (Shanghai, China) was used for validation. The median 25(OH)D serum level was 12.0 ng/mL (1.3‐60.0 ng/mL), and 40% had less than 10 ng/mL, which was defined as vitamin D deficiency. Median serum 25(OH)D levels were similar between PTCL (11.5 ng/mL) and ENKTL (12.9 ng/mL); however, vitamin D deficiency was associated with inferior survival in ENKTL but not with PTCL. The independent validation cohort (n = 115) also showed a significant association of vitamin D deficiency with poor survival in ENKTL. The 25(OH)D level had an inverse relation with inflammatory cytokines; this association had a negative effect only on survival of ENKTL, and not on PTCL. In conclusion, vitamin D deficiency was associated with inferior survival outcome of patients with ENKTL.
Long‐term comparative safety analysis of the risks associated with adding or switching to a sulfonylurea as second‐line Type 2 diabetes mellitus treatment in a US veteran population
Authors: Powell W. R. , Christiansen C. L. , Miller D. R. 
Published: October 2018

AbstractAimTo examine the risks of all‐cause mortality and cardiovascular events associated with adding vs switching to second‐line therapies in a comparative safety study of people with Type 2 diabetes mellitus.MethodsWe conducted a retrospective cohort study using an as‐treated analysis of people served by the Veterans Health Administration who were on metformin and subsequently augmented this treatment or switched to other oral glucose‐lowering treatments between 1998 and 2012. This study included 145 250 people with long follow‐up. Confounding was addressed through several strategies, involving weighted propensity score models with rich confounder adjustment and strict inclusion criteria, coupled with an incident‐user design.ResultsSecond‐line use of sulfonylureas was related to higher mortality (hazard ratio 1.39, 95% CI 1.14, 1.70) and cardiovascular risks (hazard ratio 1.19, 95% CI 1.09, 1.30) compared with thiazolidinedione therapy. Differential hazards were associated with discontinuing or not discontinuing metformin; switching to sulfonylurea therapy was associated with a higher risk of all‐cause mortality and cardiovascular events compared with all other therapies. Furthermore, add‐on sulfonylurea therapy was associated with an elevated risk for both outcomes when compared with thiazolidinedione add‐on therapy.ConclusionsThe results of the present study may inform decisions on whether to augment or discontinue metformin; when considering the long‐term risks, switching to a sulfonylurea appears unfavourable compared with other therapies. Instead, adding a thiazolidinedione to existing metformin therapy appears to be superior to adding or switching to a sulfonylurea.
Pediatric Quality of Life Inventory (PedsQL) 3.2 Diabetes Module for youth with Type 2 diabetes: reliability and validity
Authors: Varni J. W. , Delamater A. M. , Hood K. K. , Raymond J. K. , Chang N. T. , Driscoll K. A. , Wong J. C. , Yi‐Frazier J. P. , Grishman E. K. , Faith M. A. , Corathers S. D. , Kichler J. C. , Miller J. L. , Doskey E. M. , Aguirre V. P. , Heffer R. W. , Wilson D. P. ,   the Pediatric Quality of Life Inventory 3.2 Diabetes Module Testing Study Consortium
Published: October 2018

AbstractAimTo test the measurement properties of the revised and updated Pediatric Quality of Life Inventory (PedsQL) 3.2 Diabetes Module originally developed in Type 1 diabetes in youth with Type 2 diabetes.MethodsThe PedsQL 3.2 Diabetes Module and PedsQL Generic Core Scales were administered in a field test study to 100 young people aged 9–25 years with Type 2 diabetes. Factor analysis was conducted to determine the factor structure of the items.ResultsThe 15‐item Diabetes Symptoms Summary Score and 12‐item Type 2‐specific Diabetes Management Summary Score were empirically derived through factor analysis. The Diabetes Symptoms and Type 2‐specific Diabetes Management Summary Scores showed acceptable to excellent reliability across the age groups tested (α = 0.85–0.94). The Diabetes Symptoms and Type 2‐specific Diabetes Management Summary Scores evidenced construct validity through large effect size correlations with the Generic Core Scales Total Scale Score (r = 0.67 and 0.57, respectively). HbA1c was correlated with the Diabetes Symptoms and Type 2‐specific Diabetes Management Summary Scores (r = −0.13 and −0.22). Minimal clinically important difference (MCID) scores were 5.91 and 7.39 for the Diabetes Symptoms and Type 2‐specific Diabetes Management Summary Scores.ConclusionsThe PedsQL 3.2 Diabetes Module Diabetes Symptoms Summary Score and Type 2‐specific Diabetes Management Summary Score exhibited satisfactory measurement properties for use as youth self‐reported diabetes symptoms and diabetes management outcomes for clinical research and clinical practice for young people with Type 2 diabetes.
Long‐term evaluation of fitness and demographic effects of a Chinook Salmon supplementation program
Authors: Janowitz‐Koch Ilana , Rabe Craig , Kinzer Ryan , Nelson Doug , Hess Maureen A. , Narum Shawn R. 
Published: October 2018

AbstractWhile the goal of supplementation programs is to provide positive, population‐level effects for species of conservation concern, these programs can also present an inherent fitness risk when captive‐born individuals are fully integrated into the natural population. In order to evaluate the long‐term effects of a supplementation program and estimate the demographic and phenotypic factors influencing the fitness of a threatened population of Chinook Salmon (Oncorhynchus tshawytscha), we genotyped tissue samples spanning a 19‐year period (1998–2016) to generate pedigrees from adult fish returning to Johnson Creek, Idaho, USA. We expanded upon previous estimates of relative reproductive success (RRS) to include grandparentage analyses and used generalized linear models to determine whether origin (hatchery or natural) or phenotypic traits (timing of arrival to spawning grounds, body length, and age) significantly predicted reproductive success (RS) across multiple years. Our results provide evidence that this supplementation program with 100% natural‐origin broodstock provided a long‐term demographic boost to the population (mean of 4.56 times in the first generation and mean of 2.52 times in the second generation). Overall, when spawning in nature, hatchery‐origin fish demonstrated a trend toward lower RS compared to natural‐origin fish (p < 0.05). However, when hatchery‐origin fish successfully spawned with natural‐origin fish, they had similar RS compared to natural by natural crosses (first‐generation mean hatchery by natural cross RRS = 1.11 females, 1.13 males; second‐generation mean hatchery by natural cross RRS = 1.03 females, 1.08 males). While origin, return year, and body length were significant predictors of fitness for both males and females (p < 0.05), return day was significant for males but not females (p > 0.05). These results indicate that supplementation programs that reduce the potential for genetic adaptation to captivity can be effective at increasing population abundance while limiting long‐term fitness effects on wild populations.
DCL‐suppressed Nicotiana benthamiana plants: valuable tools in research and biotechnology
Authors: Katsarou Konstantina , Mitta Eleni , Bardani Eirini , Oulas Anastasis , Dadami Elena , Kalantidis Kriton 
Published: October 2018

Summary
RNA silencing is a universal mechanism involved in development, epigenetic modifications and responses to biotic and abiotic stresses. The major components of this mechanism are Dicer‐like (DCL), Argonaute (AGO) and RNA‐dependent RNA polymerase (RDR) proteins. Understanding the role of each component is of great scientific and agronomic importance. Plants, including Nicotiana benthamiana, an important plant model, usually possess four DCL proteins, each of which has a specific role, namely being responsible for the production of an exclusive small RNA population. Here, we used RNA interference (RNAi) technology to target DCL proteins and produced single and combinatorial mutants for DCL. We analysed the phenotype for each DCL knockdown plant, together with the small RNA profile, by next‐generation sequencing (NGS). We also investigated transgene expression, as well as viral infections, and were able to show that DCL suppression results in distinct developmental defects, changes in small RNA populations, increases in transgene expression and, finally, higher susceptibility in certain RNA viruses. Therefore, these plants are excellent tools for the following: (i) to study the role of DCL enzymes; (ii) to overexpress proteins of interest; and (iii) to understand the complex relationship between the plant silencing mechanism and biotic or abiotic stresses.
PD‐L1 methylation regulates PD‐L1 expression and is associated with melanoma survival
Authors: Micevic Goran , Thakral Durga , McGeary Meaghan , Bosenberg Marcus W. 
Published: October 2018

AbstractThe aim of this study is to determine the significance of programmed death ligand 1 (PD‐L1 or CD274) methylation in relation to PD‐L1 expression and survival in melanoma. Despite the clinical importance of therapies targeting the PD‐1/PD‐L1 immune checkpoint in melanoma, factors regulating PD‐L1 expression, including epigenetic mechanisms, are not completely understood. In this study, we examined PD‐L1 promoter methylation in relation to PD‐L1 expression and overall survival in melanoma patients. Our results suggest that DNA methylation regulates PD‐L1 expression in melanoma, and we identify the key methylated CpG loci in the PD‐L1 promoter, establish PD‐L1 methylation as an independent survival prognostic factor, provide proof of concept for altering PD‐L1 expression by hypomethylating agents, and uncover that PD‐L1 methylation is associated with an interferon signaling transcriptional phenotype. Based on our findings, measuring and altering PD‐L1 promoter DNA methylation may have potential prognostic and therapeutic applications in melanoma.
Dialysate sodium concentration: The forgotten salt shaker
Authors: Hanafusa Norio , Tsuchiya Ken , Nitta Kosaku 
Published: October 2018

AbstractThe concentration of sodium in dialysis fluid, a major determinant of extracellular fluid volume and blood pressure, plays a major role in the sodium balance in end‐stage renal disease patients. A low dialysate sodium concentration (DNa) reduces interdialytic weight gain (IDWG) and blood pressure and might help ameliorate endothelial dysfunction and inflammation. However, low DNa can also increase the incidence of hypotensive episodes and muscle cramps. Sodium profiling, as typically prescribed in which the DNa is ramped up from above 140 mEq/L to nonphysiological levels, might reduce hypotension in patients with hemodynamic instability but at the cost of the consequences of hypernatremia. Serum sodium concentrations of individual patients fall within a narrow range around a “sodium setpoint.” The sodium gradient, the difference between the sodium set point and the DNa, is associated more robustly with clinical outcomes than DNa itself. Sodium concentration presents several issues: the influence of the net negative charge of plasma proteins on sodium flux across the dialysis membrane (Donnan equilibrium); and the clinically important problems in measuring sodium levels. This article presents a review of the clinical effects of DNa and of basic aspects of sodium balance in hemodialysis patients.
Hemostatic profile under fluid resuscitation during rivaroxaban anticoagulation: an in vitro survey
Authors: Helin Tuukka A. , Zuurveld Marleen , Manninen Mikko , Meijers Joost C. M. , Lassila Riitta , Brinkman Herm Jan M. 
Published: October 2018

BACKGROUNDUncontrollable bleeding is the leading cause of death in traumatically injured patients. The extent to which direct factor Xa inhibitors interfere with the applied resuscitation measures is presently unknown.STUDY DESIGN AND METHODSIn this study, we investigated the effect of the resuscitation fluids saline, albumin, fresh frozen plasma (FFP) and solvent/detergent (S/D)‐treated plasma, fibrinogen concentrate, prothrombin complex concentrate (PCC), and combinations thereof on the hemostatic profile of rivaroxaban‐anticoagulated whole blood and plasma. We used rivaroxaban‐spiked whole blood and plasma from healthy donors, as well as plasma from patients on rivaroxaban, and mimicked a resuscitation approach in a 50% plasma dilution setting. Thromboelastography, thrombin generation, and fibrin generation clot lysis test were assessed using tissue factor to initiate coagulation and tissue plasminogen activator to induce clot lysis.RESULTSRivaroxaban resulted in a hypocoagulant state that remained largely unaltered upon subsequent 50% dilution with S/D‐treated plasma or FFP. Using S/D‐treated plasma as a diluent, clot stability decreased due to its low α2‐antiplasmin. Dilution with saline and albumin induced a profibrinolytic state and further deteriorated the impaired hemostatic potential of rivaroxaban‐anticoagulated blood, even after PCC and fibrinogen support. Combined use of plasma (either FFP or S/D treated) and PCC, however, considerably improved both coagulation and clot stability.CONCLUSIONIn the setting of rivaroxaban anticoagulation and major blood loss, transfusing plasma together with PCC may provide the most effective resuscitation approach with the notion that additional antifibrinolytic drug support (e.g., tranexamic acid) is likely required.
Appraising the quality standard underpinning international clinical practice guidelines for the selection and care of vascular access devices: a systematic review of reviews
Authors: Blanco-Mavillard Ian , Rodríguez-Calero Miguel Angel , Castro-Sánchez Enrique , Bennasar-Veny Miquel , De Pedro-Gómez Joan 
Published: October 2018

ObjectiveCatheter-related bloodstream infections are one of the most important adverse events for patients. Evidence-based practice embraces interventions to prevent and reduce catheter-related bloodstream infections in patients. At present, a growing number of guidelines exist worldwide. The purpose of the study was to assess clinical practice guidelines for peripheral and central venous access device care and prevention of related complications.DesignSystematic review of clinical practice guidelines: We conducted a search of the literature published from 2005 to 2018 using Medline/PubMed, Embase, CINAHL, Ovid, ScienceDirect, Scopus and Web of Science. We also evaluated grey literature sources and websites of organisations that compiled or produced guidelines. Guideline quality was assessed with the Appraisal of Guidelines for Research and Evaluation, Second Edition tool by three independent reviewers. Cohen’s kappa coefficient was used to evaluate the concordance between reviewers.ResultsWe included seven guidelines in the evaluation. The concordance between observers was substantial, K=0.6364 (95% CI 0.0247 to 1.2259). We identified seven international guidelines, which scored poorly on crucial domains such as applicability (medium 39%), stakeholder involvement (medium 65%) and methodological rigour (medium 67%). Guidelines by Spanish Health Ministry and UK National Institute for Health and Care Excellence presented the highest quality.ConclusionsIt is crucial to critically evaluate the validity and reliability of clinical practice guidelines so the best, most context-specific document is selected. Such choice is a necessary prior step to encourage and support health organisations to transfer research results to clinical practice. The gaps identified in our study may explain the suboptimal clinical impact of guidelines. Such low adoption may be mitigated with the use of implementation guides accompanying clinical documents.
Understanding the needs and experiences of people with young onset dementia: a qualitative study
Authors: Rabanal Luisa I , Chatwin John , Walker Andy , O’Sullivan Maria , Williamson Tracey 
Published: October 2018

AimDespite an estimated 40 000 people diagnosed with young onset dementia (YOD) in the UK, there is a general lack of awareness of the condition when compared with late onset dementia. The aim of this study was to explore the experiences and needs of people living with YOD (younger than 65 years) and gain an understanding of the issues that impact on them.SettingParticipants’ homes, support group premises or university rooms.Participants14 people with a diagnosis of YOD from a northern UK city.DesignSemistructured, in-depth interviews were audio recorded, transcribed and analysed cross-sectionally following principles of interpretative phenomenological analysis.ResultsFour superordinate themes are reported on ‘process of diagnosis’, ‘the impact of living YOD’, ‘needs of people with YOD’ and ‘living well with YOD’. Nine subordinate themes captured participant experiences of developing cognitive difficulties, after being diagnosed with YOD, and subsequently living with the condition. Key issues that emerging included a lack of general awareness of YOD; how this can delay help seeking; commonalities in prediagnosis trajectories; retrospective understanding of prediagnosis symptom patterns; the difficulties of obtaining a firm diagnosis; the importance of face-to-face support and difficulties associated with daily living. Participants also described the emotional and psychological impact of the condition and the importance of formal and informal support networks.ConclusionsPeople who have a diagnosis of YOD regard themselves as distinct from older people with dementia. Despite similar symptoms, the context in which they experience the condition creates a range of distinct psychosocial concerns not commonly well addressed by health and social care services. As awareness of YOD continues to grow, the development (or adaptation) of services that take into account the idiosyncratic needs of people with YOD should be addressed.