bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compressive air trapping in asthma: effects of age, sex, and severity
Authors: Sorkness Ronald L. , Kienert Casey , O’Brien Matthew J. , Fain Sean B. , Jarjour Nizar N. 
Published: March 2019

Air trapping due to airway closure has been associated with unstable asthma. In addition to airway closure that occurs at lower lung volumes during slow expiration, there may be further closure during a forced expiration because of airway compression. The purpose of this study was to define a reference range from a nonasthmatic population and investigate the characteristics of compressive air trapping in asthma. Spirometry and plethysmography were performed in 117 nonasthmatic subjects (ages 18–87 yr) and 153 asthma subjects (ages 12–72 yr). Air trapping was assessed as residual lung volume and the ratio of forced expiratory vital capacity (FVC) to slow inspiratory vital capacity (iVC) (FVC/iVC). There were no significant age or sex effects on the FVC/iVC ratio in the nonasthmatic subjects, and a fifth percentile lower limit of normal (LLN) of 0.93 was computed. An FVC/iVC ratio less than LLN defined compressive air trapping. Asthma subjects exhibited an age-related decline in the FVC/iVC ratio of 0.0027 per year ( P < 0.0001) in a mixed effects model, with additional decreases associated with severe asthma and male sex. FVC/iVC ratios< LLN were infrequent in subjects <30 yr but evident in most asthma subjects >50 yr. Lung residual volumes followed similar patterns of greater elevations in subjects with severe asthma, older age, and male sex. Compressive air trapping occurs frequently in older asthmatics, appearing to be a feature of the natural history of asthma that is greater in severe asthma and men. This component of premature airway closure affects spirometric assessment of airway function and may contribute to asthma symptoms during physical exertion. NEW & NOTEWORTHY Premature airway closure during exhalation is a component of airway obstruction that is associated with asthma severity and instability. Compressive air trapping is airway closure that is more extensive during a forced exhalation than with a slow, passive exhalation. We report that compressive air trapping occurs in most people > 50 yr with asthma, affects men more than women, and persists after bronchodilator treatment. This component of obstruction appears to be part of the natural history of asthma.
Identification of Rigosertib for the Treatment of Recessive Dystrophic Epidermolysis Bullosa–Associated Squamous Cell Carcinoma
Authors: Atanasova Velina S. , Pourreyron Celine , Farshchian Mehdi , Lawler Michael , Brown Christian A. , Watt Stephen A. , Wright Sheila , Warkala Michael , Guttmann-Gruber Christina , Hofbauer Josefina Piñón , Fuentes Ignacia , Prisco Marco , Rashidghamat Elham , Has Cristina , Salas-Alanis Julio C. , Palisson Francis , Hovnanian Alain , McGrath John A. , Mellerio Jemima E. , Bauer Johann W. , South Andrew P. 
Published: March 2019

Abstract

Purpose:
Squamous cell carcinoma (SCC) of the skin is the leading cause of death in patients with the severe generalized form of the genetic disease recessive dystrophic epidermolysis bullosa (RDEB). Although emerging data are identifying why patients suffer this fatal complication, therapies for treatment of RDEB SCC are in urgent need.
Experimental Design: We previously identified polo-like kinase 1 (PLK1) as a therapeutic target in skin SCC, including RDEB SCC. Here, we undertake a screen of 6 compounds originally designated as PLK1 inhibitors, and detail the efficacy of the lead compound, the multipathway allosteric inhibitor ON-01910, for targeting RDEB SCC in vitro and in vivo.

Results:
ON-01910 (or rigosertib) exhibited significant specificity for RDEB SCC: in culture rigosertib induced apoptosis in 10 of 10 RDEB SCC keratinocyte populations while only slowing the growth of normal primary skin cells at doses 2 orders of magnitude higher. Furthermore, rigosertib significantly inhibited the growth of two RDEB SCC in murine xenograft studies with no apparent toxicity. Mechanistically, rigosertib has been shown to inhibit multiple signaling pathways. Comparison of PLK1 siRNA with MEK inhibition, AKT inhibition, and the microtubule-disrupting agent vinblastine in RDEB SCC shows that only PLK1 reduction exhibits a similar sensitivity profile to rigosertib.

Conclusions:
These data support a "first in RDEB" phase II clinical trial of rigosertib to assess tumor targeting in patients with late stage, metastatic, and/or unresectable SCC.
Evaluating the Relationship between Interannual Variations in the Antarctic Ozone Hole and Southern Hemisphere Surface Climate in Chemistry–Climate Models
Authors: Gillett Zoe E. , Arblaster Julie M. , Dittus Andrea J. , Deushi Makoto , Jöckel Patrick , Kinnison Douglas E. , Morgenstern Olaf , Plummer David A. , Revell Laura E. , Rozanov Eugene , Schofield Robyn , Stenke Andrea , Stone Kane A. , Tilmes Simone 
Published: March 2019

AbstractStudies have recently reported statistically significant relationships between observed year-to-year spring Antarctic ozone variability and the Southern Hemisphere annular mode and surface temperatures in spring–summer. This study investigates whether current chemistry–climate models (CCMs) can capture these relationships, in particular, the connection between November total column ozone (TCO) and Australian summer surface temperatures, where years with anomalously high TCO over the Antarctic polar cap tend to be followed by warmer summers. The interannual ozone–temperature teleconnection is examined over the historical period in the observations and simulations from the Whole Atmosphere Community Climate Model (WACCM) and nine other models participating in the Chemistry–Climate Model Initiative (CCMI). There is a systematic difference between the WACCM experiments forced with prescribed observed sea surface temperatures (SSTs) and those with an interactive ocean. Strong correlations between TCO and Australian temperatures are only obtained for the uncoupled experiment, suggesting that the SSTs could be important for driving both variations in Australian temperatures and the ozone hole, with no causal link between the two. Other CCMI models also tend to capture this relationship with more fidelity when driven by observed SSTs, although additional research and targeted modeling experiments are required to determine causality and further explore the role of model biases and observational uncertainty. The results indicate that CCMs can reproduce the relationship between spring ozone and summer Australian climate reported in observational studies, suggesting that incorporating ozone variability could improve seasonal predictions; however, more work is required to understand the difference between the coupled and uncoupled simulations.
Using Radar-Derived Parameters to Develop Probabilistic Guidance for Lightning Cessation within Isolated Convection near Cape Canaveral, Florida
Authors: Patton Joseph R. , Fuelberg Henry E. 
Published: March 2019

Abstract
Thunderstorms in central Florida frequently halt outdoor activities, requiring that one wait some prescribed time after an assumed last flash before safely resuming activities. The goal of this research is to develop a high-skill probabilistic method that can be used in high pressure real-world operations to terminate lightning warnings more quickly while maintaining safety. Probabilistic guidance tools are created for isolated warm season storms in central Florida using dual-polarized radar data at 1-min intervals. The parameters examined are maximum reflectivity and graupel presence at the 0°, −5°, −10°, −15°, and −20°C levels as well as composite reflectivity. Random samples of the radar data are used to train a generalized linear model (GLM) to make a probabilistic prediction whether a given flash is the storm’s last flash. The most statistically significant predictors for lightning cessation are found to be the storm’s maximum reflectivity in the composite and the 0°C levels, along with graupel presence or absence at the −5°, −10°, −15°, and −20°C levels. Statistical verification is used to analyze the performance of the two GLMs at different probability thresholds (95.0%, 97.5%, and 99.0%). When applying the cessation guidance as though storms are occurring in real time, results showed ~99% of the storms produced no additional lightning after the GLM suggested cessation had already occurred. Although these results are encouraging, the procedure must be tested on much larger datasets having different convective modes and different areal coverages to prove its value compared to operational forecasters.
Myocardial protection and clinical outcomes in Tetralogy of Fallot patients undergoing intracardiac repair: a randomized study of two cardioplegic techniques
Authors: Negi Sunder Lal , Mandal Banashree , Singh Rana Sandeep , Puri Goverdhan Dutt 
Published: March 2019

Background: Myocardial protection in Tetralogy of Fallot patients undergoing intracardiac repair is suboptimal due to hypertrophied right ventricle. Hypertrophied myocardium is more susceptible to poor myocardial preservation because of inadequate capillary density as compared to the myocytes. There is a capillary to myocyte ratio mismatch. But del Nido Cardioplegia owing to its less viscosity is able to get more evenly distributed under hypothermic cardiopulmonary bypass as opposed to blood Cardioplegia. We hypothesized that the del Nido Cardioplegia technique, would be beneficial in myocardial protection because of its composition and method of delivery, leading into better early and late clinical outcomes in patients undergoing Tetralogy of Fallot repair as compared to blood cardioplegia reconstituted using St Thomas Cardioplegia solution. The objective of the study was to identify a better technique of myocardial preservation in Tetralogy of Fallot patient. Methods: In total, 56 Tetralogy of Fallot patients undergoing intracardiac repair under mild hypothermic cardiopulmonary bypass were randomly allocated to receive antegrade Cardioplegia with either standard blood Cardioplegia (Group I) or del Nido Cardioplegia (Group II). Preoperative as well as postoperative data including echocardiographic parameters for right ventricle functions, creatine kinase MB level, inotropic requirement, mechanical ventilation duration, intensive care unit stay and hospital mortality were evaluated. Results: Inotropic score in the first 24 hours postoperatively was significantly lower in Group II compared to Group I (13.4 ± 7.2 vs. 21.2 ± 9.6, p = 0.003). Creatine kinase MB level (ng/mL) was comparable between the groups. Echocardiographic parameters for right ventricle functions were also comparable between the groups during early as well as after 3 to 6 months postoperatively. Conclusion: Del Nido Cardioplegia is equally efficacious in providing myocardial protection during intracardiac repair under mild hypothermic cardiopulmonary bypass in Tetralogy of Fallot patients as compared to blood Cardioplegia solution with the added benefit of reducing inotropic requirement in first 24 hours postoperative period.
Socioeconomic factors affecting access to preferred place of death: A qualitative evidence synthesis
Authors: Turner Victoria , Flemming Kate 
Published: March 2019

Background: Existing quantitative evidence suggests that at a population level, socioeconomic factors affect access to preferred place of death. However, the influence of individual and contextual socioeconomic factors on preferred place of death are less well understood. Aim: To systematically synthesise the existing qualitative evidence for socioeconomic factors affecting access to preferred place of death in the United Kingdom. Design: A thematic synthesis of qualitative research. Data sources: Cochrane Library, MEDLINE, Embase, CINAHL, ASSIA, Scopus and PsycINFO databases were searched from inception to May 2018. Results: A total of 13 articles, reporting on 12 studies, were included in the synthesis. Two overarching themes were identified: ‘Human factors’ representing support networks, interactions between people and decision-making and ‘Environmental factors’, which included issues around locations and resources. Few studies directly referenced socioeconomic deprivation. The main factor affecting access to preferred place of death was social support; people with fewer informal carers were less likely to die in their preferred location. Other key findings included fluidity around the concept of home and variability in preferred place of death itself, particularly in response to crises. Conclusion: There is limited UK-based qualitative research on socioeconomic factors affecting preferred place of death. Further qualitative research is needed to explore the barriers and facilitators of access to preferred place of death in socioeconomically deprived UK communities. In practice, there needs to be more widespread discussion and documentation of preferred place of death while also recognising these preferences may change as death nears or in times of crisis.
Cellular Components and Growth Factor Content of Platelet-Rich Plasma With a Customizable Commercial System
Authors: Baria Michael , Vasileff W. Kelton , Miller Meghan , Borchers James , Flanigan David C. , Durgam Sushmitha S. 
Published: March 2019

Background: Platelet-rich plasma (PRP) is an autologous orthobiologic treatment option for musculoskeletal conditions with favorable results in a limited number of high-quality clinical trials. Because different blood-processing methods result in PRP with varying cellular and growth factor content, it is critical that clinicians understand the content of the specific PRP being used in clinical practice. One adjustable system, the Angel System, has few independent laboratory reports on the specific composition of its PRP. The goal of this study was to quantify the cellular and growth factor composition of PRP produced by this system at its lowest hematocrit settings. Hypothesis: The authors hypothesized that the system would significantly concentrate platelets over baseline and, at the lowest hematocrit settings, would reduce leukocytes to produce leukocyte-poor PRP. Study Design: Descriptive laboratory study. Methods: Ten healthy male volunteers donated 150 mL of whole blood for processing. Three separate processing cycles were performed for each sample at the 0%, 1%, and 2% hematocrit settings. The resultant PRP from each cycle was sent for complete blood counts and enzyme-linked immunosorbent assay to quantify the following growth factors: platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF). Results: The system consistently concentrated platelets 5-fold over baseline, with no significant differences among settings. Leukocytes were concentrated at all settings, between 2 and 5 times over baseline. The 0% and 1% settings had significantly lower leukocyte concentrations than the 2% setting. Lymphocytes made up >89% of the leukocyte differential, while neutrophils represented <11% of the differential at each setting. There was a significant increase in PDGF and bFGF, a significant decrease in IGF-1, and no change in VEGF, with no difference among settings. Conclusion: The system consistently concentrated platelets 5 times but was unable to reduce leukocytes, therefore resulting in leukocyte-rich PRP at each setting tested. Leukocytes had a differential composition of >89% lymphocytes and <11% neutrophils. For all settings, PDGF and bFGF were concentrated; IGF-1 was reduced; and VEGF was not significantly different from baseline. Clinical Relevance: These data can serve to guide clinicians considering using this particular PRP system. It consistently yielded leukocyte-rich PRP with a lymphocyte-predominant/neutrophil-reduced profile. Further research is needed to better understand how to apply this specific PRP in clinical practice.
Are There Missed Opportunities to Maximize Organ Donation Registrations? An Examination of Driver’s License Applications Across the United States
Authors: Stevens Jack , Tumin Dmitry , Shaffer Kelly L. , Bickman Leonard , Hoagwood Kimberly E. , Hayes Don 
Published: March 2019

Introduction: With 116 000 people waiting for transplants and 8000 patients dying annually on waiting lists, the United States has a considerable organ shortage. An insufficient number of Americans have registered to become organ donors when obtaining driver’s licenses or ID cards. Across states, there is considerable variability in organ donor registration rates as well as driver’s license applications. Methods: The purpose of this project was to describe the variability in the phrasing of the organ donor registration question by state bureaus of motor vehicles as well as other application questions that might influence this decision. In particular, the frequency of states employing empirically supported messages to increase donor registrations was ascertained. The content and phrasing of 46 different driver’s license applications was coded in regard to seeking organ donor registrations. Findings: No states used the empirically supported strategies of reciprocity, descriptive norms, or loss/gain framing from the interdisciplinary field of behavioral economics. Twelve states used injunctive norms to signify social approval for organ donation. Many state applications had lengthy organ donation sections and health questions that could discourage donor registrations. Discussion: There is an extremely low use of empirically supported messages to increase organ donation registrations in driver’s license applications in the United States. Opportunities exist for thoughtful consideration of the wording of driver’s license applications. States interested in exploring ways to increase donations could undertake controlled variation of applications to test the effects of message framing on registration rates.
Incidence, Risk Factors, Clinical Management, and Outcomes of Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients
Authors: Liu Michelle , Husain Shahid , Famure Olusegun , Li Yanhong , Kim S. Joseph 
Published: March 2019

Background: Posttransplant lymphoproliferative disorder (PTLD) is a severe complication after kidney transplantation. This study examined the incidence, risk factors, clinical management, and outcomes of PTLD in a cohort of kidney transplant recipients. Design: This single-center cohort study included 1642 patients transplanted from January 1, 2000, to December 31, 2012, with follow-up until December 31, 2013. The incidence and risk factors for PTLD were examined using a Cox proportional hazards model. A Cox model was also used to assess the association of PTLD and graft outcomes. Results: Sixteen recipients developed PTLD over follow-up. The incidence rate was 0.18 (95% confidence interval [CI]: 0.11-0.29) cases per 100 person-years. Four were from Epstein–Barr virus (EBV) mismatched (D+/R−) transplants and 12 from EBV-positive recipients (R+). Recipients with D+/R− matches were at a significantly higher risk of developing PTLD than R+ (hazard ratio [HR]: 7.52 [95% CI: 2.42-23.32]). Fifteen cases had immunosuppression reduced, 11 cases were supplemented with rituximab or ganciclovir, 6 cases required chemotherapy or radiation, and 6 cases had tumors excised. By the end of follow-up, 6 patients went into remission, 5 returned to chronic dialysis, and 5 patients died. Patients with PTLD were significantly more likely to have total graft failure (return to chronic dialysis, preemptive retransplant, or death with graft function) than patients without PTLD (HR: 3.41 [95% CI: 1.72-6.78). Discussion: Epstein–Barr virus mismatch continues to be a strong risk factor for developing PTLD after kidney transplantation. Recipients with PTLD have a poor prognosis, as the optimal management remains to be elucidated.
Impact of rural versus urban geographic location on length of stay after carotid endarterectomy
Authors: Minc Samantha D , Misra Ranjita , Holmes Sari D , Ren Yue , Marone Luke 
Published: March 2019

Background Reducing the incidence of extended length of stay (ELOS) after carotid endarterectomy (CEA), defined as LOS > 1 day, is an important quality improvement focus of the Vascular Quality Initiative (VQI). Rural patients with geographic barriers pose a particular challenge for discharge and may have higher incidences of ELOS as a result. The purpose of this study was to examine the impact of patients’ home geographic location on ELOS after CEA. Methods The VQI national database for CEA comprised the sample for analyses ( N = 66,900). Rural-Urban Commuting Area (RUCA) codes, a validated system used to classify the nation’s census tracts according to rural and urban status, was applied to the VQI database and used to indicate patients’ home geographic location. LOS was categorized into two groups: LOS ≤ 1 day (66%) and LOS > 1 day (ELOS) (34%). Multivariable logistic regression was conducted to examine the effect of geographic location on ELOS after adjustment for age, gender, race, and comorbid conditions. Results A total of 66,900 patients were analyzed and the mean age of the sample was 70.5 ± 9.3 years (40% female). After adjustment for covariates, the urban group had increased risk for ELOS (OR = 1.20, p < 0.001). Other factors that significantly increased risk for ELOS were non-White race/Latinx/Hispanic ethnicity (OR = 1.44, p < 0.001) and nonelective status (OR = 3.31, p < 0.001). In addition, patients treated at centers with a greater percentage of urban patients had greater risk for ELOS (OR = 1.008, p < 0.001). Conclusions These analyses found that geographic location did impact LOS, but not in the hypothesized direction. Even with adjustment for comorbidities and other factors, patients from urban areas and centers with more urban patients were more likely to have ELOS after CEA. These findings suggest that other mechanisms, such as racial disparities, barriers in access to care, and disparities in support after discharge for urban patients may have a significant impact on LOS.
Memantine selectively prevented the induction of dynamic allodynia by blocking Kir2.1 channel and inhibiting the activation of microglia in spinal dorsal horn of mice in spared nerve injury model
Authors: Chen Yangyang , Shi Yiqian , Wang Guoxiang , Li Yimei , Cheng Longzhen , Wang Yun 
Published: March 2019

Background Memantine is one of the important clinical medications in treating moderate to severe Alzheimer disease. The effect of memantine on preventing or treating punctate allodynia has been thoroughly studied but not on the induction of dynamic allodynia. The aim of this study is to investigate whether memantine could prevent the induction of dynamic allodynia and its underlying spinal mechanisms. Results (1) In in vivo spared nerve injury pain model, pretreatment with memantine at a lower dose (10 nmol, intrathecal; memantine-10) selectively prevented the induction of dynamic allodynia but not the punctate allodynia. (2) Pretreatment with either MK801-10 (MK801-10 nmol, intrathecal) or higher dose of memantine (30 nmol, intrathecal; memantine-30) prevented the induction of both dynamic and punctate allodynia. (3) Memantine-10 showed significant effect on the inhibition of the spared nerve injury-induced overactivation of microglia in spinal dorsal horn. (4) In contrast, in complete freund′s adjuvant (CFA) model, memantine-10 neither affected the CFA injection-induced activation of microglia in spinal dorsal horn nor the induction of dynamic allodynia. (5) Immunohistological studies showed Kir2.1 channel distributed widely and co-localized with microglia in the spinal dorsal horn of mice. (6) Pretreatment with either minocycline, a microglia inhibitor, or ML133, a Kir2.1 inhibitor, both selectively prevented the overactivation of microglia in spinal dorsal horn and the induction of dynamic allodynia following spared nerve injury. Conclusion The selective inhibitory effect on the induction of dynamic allodynia in spared nerve injury model by low dose of the memantine (memantine-10) was tightly correlated with the blockade of microglia Kir2.1 channel to suppress the microglia activation.