bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Comorbidity on Symptoms and Quality of Life Among Patients Being Treated for Breast Cancer
Authors: Wu Horng-Shiuann , Davis Jean E. , Chen Ling 
Published: June 2018

Background
Cancer patients often have other noncancer medical conditions. Presence of comorbidities negatively affects cancer survival.

Objective
The aim of this study was to investigate comorbidity, risk factors for comorbidity, and how comorbidity was associated with symptoms and quality of life in patients being treated for breast cancer.

Methods
One hundred and one breast cancer chemotherapy outpatients completed this study. Comorbid conditions, weight, height, and smoking status were identified by chart review. Symptoms and quality of life were self-reported using psychometrically sound instruments. Log-linear regression analyses with age as the covariate examined impact of ethnicity, body mass index (BMI), and smoking on comorbidities.

Results
Approximately 84% of the participants had 1 or more comorbid conditions. Adjusting for age, number of comorbidities differed by BMI (P = .000); the obese group had significantly more comorbidities than the normal and overweight groups. The interaction between BMI and smoking was significant (P = .047). The obese participants who smoked had significantly more comorbidities compared with those who were obese but did not smoke (P = .001). More comorbid conditions were associated with greater pain (P < .05) and poorer sleep quality (P < .05). Comorbidity significantly correlated with symptoms and functional aspects of quality of life (P < .01 and P < .05, respectively). A greater number of comorbidities was associated with lower physical and role functioning and worse fatigue, dyspnea, appetite loss, and nausea and vomiting (all P < .05).

Conclusions
Comorbidity exerts negative impacts on symptoms and quality of life. Weight and smoking status are strong determinants of breast cancer comorbidity.

Implications for Practice
Personalized care planning, weight management, and smoking cessation may lead to better cancer outcomes.
Admission Hyperoxia Is a Risk Factor for Mortality in Pediatric Intensive Care*
Authors: Numa Andrew , Aneja Himanshu , Awad John , Ravindranathan Hari , Singh Puneet , Swil Kevin , Williams Gary 
Published: June 2018

Objectives:
To determine whether the association between hyperoxia and increased risk-adjusted mortality in adult intensive care patients is also observed in a pediatric intensive care population.

Design:
Single-center retrospective analysis of admissions to ICU over a 5-year period commencing January 1, 2012, examining the relationship between Pao
2 measured within the first hour of admission and risk-adjusted mortality. Standardized mortality rates were calculated using the Pediatric Index of Mortality-3, and patients were grouped into 50 mm Hg (6.67 kPa) Pao
2 bands to assess the relationship between initial Pao
2 and risk-adjusted mortality.

Setting:
Tertiary PICU with 17 beds and 1,100 annual admissions located in metropolitan Sydney, Australia.

Patients:
A total of 1,447 patients 0–18 years old with Pao
2 recorded at admission to the ICU.

Interventions:
None.

Measurements and Main Results:
There were 5,176 patients admitted to the ICU during the study period and 1,447 (28%) with Pao
2 recorded at admission. A U-shaped relationship between raw mortality and admission Pao
2 was observed, with lowest mortality (2.3% and 2.6%, respectively) observed in the 101–150 (13.5–20.0 kPa) and 151–200 mm Hg (20.1–26.7 kPa) bands and the highest mortality observed in patients with Pao
2 less than 50 mm Hg (6.67 kPa) with mortality of 5.3%, or greater than 350 mm Hg (46.7 kPa) with mortality of 18.2%. Hyperoxia at admission was associated with an increase in risk-adjusted mortality, with polynomial regression indicating a strong correlation between Pao
2 band and risk-adjusted outcome (r
2 = 0.845). When included in a multivariate model that included the Pediatric Index of Mortality-3 variables, the odds ratio for hyperoxia (defined as Pao
2 > 250 mm Hg [33.3 kPa]) predicting death was 2.66 (p = 0.047).

Conclusions:
In this single-center study, hyperoxia at admission to the PICU was highly correlated with increased risk-adjusted mortality. Further investigation of these observations in a large multicenter cohort is warranted.
Short-Term Effects of Normocapnic Hyperpnea and Exercise Training in Patients With Chronic Obstructive Pulmonary Disease
Authors: Paneroni Mara , Simonelli Carla , Saleri Manuela , Trainini Debora , Fokom Georges , Speltoni Ilaria , Piaggi Giancarlo , Ambrosino Nicolino , Vitacca Michele 
Published: June 2018

Objective
The aim of the study was to evaluate the short-term physiologic effects of respiratory muscle training with normocapnic hyperpnea added to standard exercise training on respiratory muscle endurance/strength and exercise tolerance in patients with chronic obstructive pulmonary disease.

Design
The study used a randomized controlled trial. Patients referred for rehabilitation were randomly assigned to 20 sessions (twice daily 5 d/wk) of either normocapnic hyperpnea (group 1, n = 12) or sham maneuvers (group 2, n = 10) in addition to individualized cycle training and abdominal, upper, and lower limb muscle exercise. At baseline and end of study, patients underwent evaluation of respiratory muscle endurance, maximum voluntary ventilation, maximal inspiratory, and expiratory pressures, and 6-min walking distance.

Results
After training, a significant improvement was found only for group 1 in respiratory muscle endurance time (by 654 [481] secs versus 149 [216] secs for group 2, P = 0.0108) and maximal inspiratory (group 1: from 81.2 [21.9] cmH2O to 107.6 [23.0] cmH2O, P = 0.018 versus group 2: from 75.4 [13.8] cmH2O to 81.3 [18.9] cmH2O, P = 0.139). The difference between groups for 6-min walking distance, maximum voluntary ventilation, and expiratory pressures was not significant.

Conclusions
Short-term normocapnic hyperpnea training added to standard exercise, compared with exercise training alone, improves respiratory muscle endurance and strength but not exercise tolerance in patients with chronic obstructive pulmonary disease.
Treatment of Digital Melanonychia with Atypia
Authors: Lans Jonathan , van Leeuwen Wouter , Jupiter Jesse B. , Eberlin Kyle R. 
Published: June 2018

Background:
Melanonychia of the digit is uncommon in the Caucasian population and is concerning because of potential malignant transformation. Several histologic changes occur before malignant transformation, including melanocytic atypia. The authors evaluated patients with melanonychia with melanocytic hyperplasia to determine the risk factors for malignant transformation.

Methods:
The authors retrospectively reviewed records for patients older than 18 years that underwent biopsy for melanonychia. They identified 22 patients with melanocytic hyperplasia with a median age of 61 years (interquartile range, 44 to 71 years). A bivariate analysis was performed to evaluate whether the degree of atypia was associated with malignant transformation and whether treatment choices by surgeons were based on melanocytic atypia.

Results:
Following biopsy, patients were followed for a median of 41.0 months (interquartile range, 4.8 to 100.6 months). Melanocytic atypia was present in nine patients and transformed into a malignancy in three: in two patients it became a melanoma in situ, and in one it became an acral lentiginous melanoma. Moderate-severe and severe melanocytic atypia was associated with malignant transformation. After initial biopsy, 14 patients were monitored (11 without atypia and three with atypia). One patient with slight atypia, two patients with moderate-severe atypia, and two patients with severe atypia underwent additional treatment. Patients with melanocytic hyperplasia without atypia were monitored more often (78.6 percent versus 21.4 percent).

Conclusions:
Melanonychia presents a challenge to the hand surgeon, as some patients may be monitored and some should undergo additional resection. Patients with moderate-severe melanocytic atypia following biopsy should undergo resection, and those with mild to slight atypia can most often be monitored clinically.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Mobile Apps for Individuals With Rheumatoid Arthritis
Authors: Luo Dee , Wang Penny , Lu Fengxin , Elias Josephine , Sparks Jeffrey A. , Lee Yvonne C. 
Published: June 2018

Background
Mobile health applications (apps) have the potential to help individuals with chronic illnesses learn about, monitor, and manage their condition, but these apps are largely unexamined, with the state and direction of development unclear.

Objective
We performed a systematic review of publicly available apps, directed toward individuals with rheumatoid arthritis (RA); described their current features; and determined areas of unmet need.

Methods
We searched the iTunes and Google Play App Stores for the term “arthritis” and reviewed the descriptions of these apps for specific mentions of RA. Applications that met inclusion criteria were downloaded and reviewed. Using a set of quality measures identified from literature review, we assessed each app for 4 features: basic characteristics, content source, functionality, and security. Frequencies for each feature were recorded, and percentages were calculated.

Results
Twenty apps intended for use by RA patients were identified in December 2016. Fifty percent of apps (n = 10) offered only symptom tracking. Five (20%) provided only information about RA, and 5 (20%) engaged patients by providing both symptom tracking and educational information. Fewer than 50% of apps provided means to contact health care providers or link to an online community, and only 6 (30%) offered security protection for the user.

Conclusions
Most current RA apps do not provide a comprehensive experience for individuals with RA. Areas for optimization include the implementation of smartphone accessibility features and secure methods of protecting individual health information.
Factors Associated With Inadequate Intraoperative Baseline Lower Extremity Somatosensory Evoked Potentials
Authors: Chen Jonathan H. , Shilian Parastou , Cheongsiatmoy Justin , Gonzalez Andres A. 
Published: June 2018

Purpose:
Intraoperative neurophysiologic monitoring involves the use of various modalities, including somatosensory evoked potentials (SEP), to assess the integrity of the at-risk nervous system during surgeries. Reliable baseline tracings are important because they are data against which future tracings are compared to detect potential injury. In some cases, adequate baselines may be difficult to achieve. Therefore, we analyzed several patient-specific factors to determine which variables are associated with inadequate intraoperative SEP baseline signals.

Methods:
This is a single-center, retrospective chart review of 631 consecutive patients who underwent spine or cranial surgeries between 2010 and 2011. Variables analyzed included age, glucose levels, diabetes mellitus type 2, hypertension, hyperlipidemia, height, weight, sex, smoking, preexisting neurologic conditions, surgical history, lower extremity edema, and neurologic examination findings. Association between these patient factors and baseline lower extremity SEP signals were analyzed.

Results:
Height, weight, neurologic deficits, lower extremity edema, and history of neurologic disease are each associated with inadequate baseline lower extremity SEPs after controlling for confounding variables. Baseline signals were able to be acquired in 94.1% of patients.

Conclusions:
Adequate baselines are paramount for successful intraoperative neurophysiologic monitoring. However, certain patient-specific factors are associated with inadequate baseline SEP signals. Physical examination findings and a detailed chart review can be done to identify these factors and guide expectations during monitoring. Further research related to patient-specific factors amenable to modification can further improve our capacity to protect the nervous system during surgery.
Multiparametric Signature of Glioblastoma Differentiation Revealed by Imaging of Cellular Epigenetic Landscapes
Authors: Farhy Chen , Hariharan Santosh , Ylanko Jarkko , Woudenberg Lotte van , Cimadamore Flavio , Ugarte Fernando , Forsberg Camilla , Huang Chun-Teng , Andrews David W. , Terskikh Alexey V. 
Published: June 2018

AbstractThe resistance of Glioblastoma (GBM) to conventional cytotoxic drugs has prompted novel therapeutic strategies, including differentiating tumor propagating cells (TPCs) into less tumorigenic cells using small molecule inducers of TPC differentiation. However, high-throughput screening for such molecules is hampered by the lack of robust markers of GBM differentiation. To obtain a signature of differentiated TPCs, we developed “Microscopic Imaging of Epigenetic Landscapes” (MIEL), which captures patterns of nuclear staining for epigenetic marks to derive feature-fingerprints of individual cells. We confirmed MIEL’s ability to accurately distinguish multiple cell fates and identified a multiparametric epigenetic signature of differentiated TPCs. Critically, we validated epigenetic imaging-based signature using global gene expression thus providing the proof of principle for the MIEL’s ability to select and prioritize small molecules, which induce TPC differentiation.
Validation and automation of a high-throughput multi-targeted method for semi-quantification of endogenous metabolites from different biological matrices using tandem mass spectrometry
Authors: Nandania Jatin , Peddinti Gopal , Pessia Alberto , Kokkonen Meri , Velagapudi Vidya 
Published: June 2018

AbstractThe use of metabolomics profiling to understand metabolism under different physiological states has increased in recent years, which created the need for robust analytical platforms. Here, we present a validated method for targeted and semi-quantitative analysis of 102 polar metabolites that covers major metabolic pathways from 24 classes in a single 17.5-min assay. The method has been optimized for a wide range of biological matrices from various organisms, and involves automated sample preparation, and data processing using in-house developed R package. To ensure reliability, the method was validated for accuracy, precision, selectivity, specificity, linearity, recovery, and stability according to European Medicines Agency guidelines. We demonstrated excellent repeatability of the retention times (CV<4%), calibration curves (R2≥0.980) in their respective wide dynamic concentration ranges (CV<3%), and concentrations (CV<25%) of quality control samples interspersed within 25 batches analyzed over a period of one-year. The robustness was demonstrated through high correlation between metabolite concentrations measured using our method and NIST reference values (R2=0.967), including cross-platform comparability against the BIOCRATES AbsoluteIDQp180 kit (R2=0.975) and NMR analyses (R2=0.884). We have shown that our method can be successfully applied in many biomedical research fields and clinical trials, including epidemiological studies for biomarker discovery. In summary, a thorough validation demonstrated that our method is reproducible, robust, reliable, and suitable for metabolomics studies.
Spatial-temporal clustering analysis of yaws on Lihir Island, Papua New Guinea to enhance planning and implementation of eradication programs
Authors: Mooring Eric Q. , Mitjà Oriol , Murray Megan B. 
Published: June 2018

AbstractBackgroundIn the global program for the eradication of yaws, assessments of the prevalence of the disease are used to decide where to initiate mass treatment. However, the smallest administrative unit which should be used as the basis for making decisions is not clear. We investigated spatial and temporal clustering of yaws to help inform the choice of implementation unit.Methodology/Principal findingsWe analyzed 11 years of passive surveillance data on incident yaws cases (n = 1448) from Lihir Island, Papua New Guinea. After adjusting for age, sex, and trends in health-seeking, we detected three non-overlapping spatiotemporal clusters (p < 1 × 10−17, p = 1.4 × 10−14, p = 1.4 × 10−8). These lasted from 28 to 47 months in duration and each encompassed between 4 and 6 villages. We also assessed spatial clustering of prevalent yaws cases (n = 532) that had been detected in 7 biannual active case finding surveys beginning in 2013. We identified 1 statistically significant cluster in each survey. We considered the possibility that schools that serve multiple villages might be loci of transmission, but we found no evidence that incident cases of yaws among 8- to 14-year-olds clustered within primary school attendance areas (p = 0.684).Conclusions/SignificanceThese clusters likely reflect transmission of yaws across village boundaries; villages may be epidemiologically linked to a degree such that mass drug administration may be more effectively implemented at a spatial scale larger than the individual village.Author SummaryThe World Health Organization aims to eradicate yaws using mass drug administration (MDA), which consists of treating everyone in an administrative unit with antibiotics. The administrative unit in a country which is used as the basis for making decisions about implementing MDA is called the implementation unit. Prevalence assessments are used to identify endemic communities for mass treatment programs, but the spatial scale (e.g. village, sub-district, district, or province) at which mass treatment should be implemented is currently unclear. The choice of implementation unit depends on many factors; one of these is the underlying transmission patterns of the disease. Using data from Lihir Island, Papua New Guinea, we found that geographic clusters of yaws often spanned multiple villages. These clusters likely reflect transmission of the infectious disease across village boundaries and suggest that it may be best to implement MDA at a spatial scale larger than the individual village, for example at sub-district level.
Infectious bronchitis virus attaches to lipid rafts and enters cells via clathrin mediated endocytosis
Authors: Wang Huan , Sun Yingjie , Mao Xiang , Meng Chunchun , Tan Lei , Song Cuiping , Qiu Xusheng , Ding Chan , Liao Ying 
Published: June 2018

ABSTRACTDue to its economic importance to in poultry industry, the biology and pathogenesis of infectious bronchitis virus (IBV) have been investigated extensively. However, the molecular mechanisms involved in IBV entry are not well characterized. In this study, systematic approaches were used to dissect IBV entry process in various susceptible cells. First, we observed that lipid rafts were involved in IBV attachment. Second, low pH in intracyplasmic vesicles was required for virus entry. By using the specific clathrin mediated endocytosis (CME) inhibitor or knock down of clathrin heavy chain (CHC), we demonstrated that IBV mainly utilized the CME for its entry. Furthermore, GTPase dynamin1 was involved in virus containing vesicle scission and internalization. Surprisingly, CME adaptor Eps15 had no effect on IBV internalization. Third, the penetration of IBV into cells led to active cytoskeleton rearrangement. After internalization, virus particles moved along with the classical endosome/lysosome track, as evidenced by co-localization of R18 labeled IBV with vehicle markers Rab5/Rab7/LAMP1 along with the infection time course. Functional inactivation of Rab5 and Rab7 significantly inhibited IBV infection. VCP, a protein helps early endosome maturation, was involved virus trafficking. Finally, by using the dual R18/DiOC labeled IBV, we observed that membrane fusion with late endosome/lysosome membranes was induced between 2-3 h.p.i.. Taken together, our findings demonstrate that IBV virions attach to lipid rafts and are internalized into cells via CME, move along with early/late endosomes-lysosomes, finally fuse with late endosome-lysosome membranes, release virus genome into cytoplasm. This study provides comprehensive images of IBV attachment-internalization-trafficking-fusion steps.IMPORTANCEIBV, the avian coronavirus isolated in 1937, infects chicken and causes economic loss in poultry industry. It has been reported that the entry of IBV requires low pH. However, the molecular mechanisms underlying IBV internalization and trafficking remain to be clarified. Therefore, we employed multiple chemical and molecular approaches to dissect the entry mechanisms of IBV in susceptible cells. Our results showed IBV entry was significantly inhibited when clathrin-mediated endocytosis (CME) was blocked by chemical inhibitor or depletion of clathrin protein. Moreover, by using R18-labeled IBV, we found that IBV particles attached to lipid rafts, led to actin rearrangement, and moved along with the entire endosomal system. R18/DiOC labeling method showed that IBV fused with late endosomes or lysosomes. This is the first report to describe the entire entry process of IBV, allowing for a better understanding of the infection process of group III avian coronavirus.
High resolution profile of body wide pathological changes induced by abnormal elastin metabolism in Loxl1 knockout mice
Authors: Wu Bingbing , Li Yu , An Chengrui , Jiang Deming , Gong Lin , Liu Yanshan , Liu Yixiao , Li Jun , Ouyang HongWei , Zou XiaoHui 
Published: June 2018

AbstractAbnormal ECM caused serious body wide diseases and elastin is one of the important ECM components. But its systemic function still has not yet been thoroughly illustrated due to limitations related to novel research technologies. To uncover the functions of elastin, a new method for body-wide organ transcriptome profiling, combined with single-cell mass cytometry of the blood, was developed. A body-wide organ transcriptomic (BOT) map was created by performing RNA-seq of 17 organs from both Loxl1 knockout (KO) and wide type (WT) mice. The BOT results showed a systematic up-regulation of genes related to immune response and proliferation process in multiple tissues of the KO mice; histological and immune staining also confirmed the hyperplasia and infiltration of local immune cells in the vagina, small intestine, and liver tissues of KO mice. Furthermore, using 32 markers, CYTOF mass cytometry analysis of the immune cell subpopulations from the peripheral blood revealed apparent systemic immune changes in the KO mice; data showed an activated NK cells and T cells with a higher expression of CD44 and CD38, and a suppressed B cells, macrophages and neutrophils with lower expressions of CD62L, CD44 and IL6. More interestingly, these findings also correlated well with the data obtained from cancer patient databases; tumor patients had higher mutation frequency of Loxl1, and the Loxl1-mutant tumor patients had up-regulated immune process, cell proliferation and decreased survival rate. Thus, this research provided a powerful strategy to screen body-wide organ functions of a particular gene; the findings also illustrated the important biological roles of elastin on multiple organ cells and systemic immunity. These strategy and discoveries are both of important value for the understanding of ECM biology and multi-organ cancer pathology.