bluuebunny/crossref_metadata_2025_split huggingface dataset:
National incidence and initial therapy for thymic carcinoma in Japan: based on analysis of hospital-based cancer registry data, 2009–2015
Authors: Koizumi Tomonobu , Otsuki Kengo , Tanaka Yuriko , Noguchi Takuro , Fukushuima Toshirou , Kobayashi Takashi , Ozawa Takesumi , Sekiguchi Nodoka , Hamanaka Kazutoshi 
Published: January 2020

Abstract

Background
Although thymic carcinoma is a rare epithelial neoplasm that tends to be aggressive and metastasize widely, its incidence in Japan remains unclear. This study was to examine the incidence and initial treatment of thymic carcinoma in the Japanese population using data from a hospital-based cancer registry.

Methods
Using data from the national database of hospital-based cancer registries, we examined the incidence and initial treatment of thymic carcinoma diagnosed and treated in designated and non-designated cancer care hospitals between 2009 and 2015. Based on Japanese population estimates, we calculated the incidence rate of thymic cancer in Japan.

Results
A total of 2587 thymic carcinoma cases were diagnosed between 1 January 2009 and 31 December 2015. These patients consisted of 1705 (66%) men and 882 (34%) women, with a median age of 65.5 years (range, 16–96 years). The number and proportion of thymic carcinoma to all registered cancer cases per year increased each year. The incidence rate was estimated to be 0.29/100000 during the observation period, with an annual onset incidence of 0.38/100000 in 2015. Almost half of all cases of thymic carcinoma were treated surgically, while the others were treated with non-surgical therapy consisting of chemotherapy with or without radiotherapy.

Conclusions
We estimated the incidence rate of thymic carcinoma in Japan based on the designated cancer care hospital-based cancer registry. The half of all patients with thymic carcinoma was unfit for multimodality therapy, including thoracic surgery.
Impact of RhoA overexpression on clinical outcomes in cervical squamous cell carcinoma treated with concurrent chemoradiotherapy
Authors: Tanaka Keiichi , Matsumoto Yoshitaka , Ishikawa Hitoshi , Fukumitsu Nobuyoshi , Numajiri Haruko , Murofushi Keiko , Oshiro Yoshiko , Okumura Toshiyuki , Satoh Toyomi , Sakurai Hideyuki 
Published: January 2020

Abstract
The Rho-associated coiled-coil-containing protein kinase (ROCK) pathway is known to influence metastasis in several cancers; however, the impact of the pathway on clinical outcomes in patients undergoing radiotherapy remains unknown. In the present study, the expression of RhoA, RhoC, ROCK-1, ROCK-2 and p53 was immunohistochemically evaluated using biopsy specimens obtained from 49 patients with stage II–III cervical squamous cell carcinoma treated with concurrent chemoradiotherapy (CCRT). The relationship between the expression of these proteins and patient outcomes was investigated. RhoA overexpression was associated with significantly impaired disease-free survival and distant metastasis-free survival (P = 0.045 and P = 0.041, respectively) in stage III cancer patients. No differences in survival were observed based on the expression of the other proteins among stage III cancer patients. In stage II cancer patients, no differences in survival were noted based on the expression of any of the proteins. The expression of RhoA was able to successfully differentiate cervical cancer patients with distant metastasis after CCRT. This information may help stratify patients according to the risk of metastasis, thereby leading to the potential to provide individualized treatment.
Dynamic evolution of sentiments in Never Let Me Go: Insights from multifractal theory and its implications for literary analysis
Authors: Hu Qiyue , Liu Bin , Thomsen Mads Rosendahl , Gao Jianbo , Nielbo Kristoffer L 
Published: January 2020

Abstract
The moods, feelings, and attitudes represented in a novel will resonate in the reader by activating similar sentiments. It is generally accepted that sentiment analysis can capture aspects of such moods, feelings, and attitudes and can be used to summarize a novel’s plot in a story arc. With the availability of a number of algorithms to automatically extract sentiment-based story arcs, new approaches for their utilization becomes pertinent. We propose to use nonlinear adaptive filtering and fractal analysis in order to analyze the narrative coherence and dynamic evolution of a novel. Using Never Let Me Go by Kazuo Ishiguro, the winner of the 2017 Nobel Prize for Literature as an illustrative example, we show that: (1) nonlinear adaptive filtering can extract a story arc that reflects the tragic trend of the novel; (2) the story arc displays persistent dynamics as measured by the Hurst exponent at short and medium timescales; (3) the plot’s dynamic evolution is reflected in the time-varying Hurst exponent. We argue that these findings are indicative of the potential that multifractal theory has for computational narratology and large-scale literary analysis. Specifically that the global Hurst exponent of a story arc is an index of narrative coherence that can identify bland, incoherent, and coherent narratives on a continuous scale. And, further, that the local time-varying Hurst exponent captures variation of a novel’s plot such that the extrema have specific narratological interpretations.
Clinical relevance of Scedosporium spp. and Exophiala dermatitidis in patients with cystic fibrosis: A nationwide study
Authors: de Jong C C M , Slabbers L , Engel T G P , Yntema J B , van Westreenen M , Croughs P D , Roeleveld N , Brimicombe R , Verweij P E , Meis J F , Merkus P J 
Published: January 2020

AbstractAn increased prevalence of various filamentous fungi in sputum samples of patients with cystic fibrosis (CF) has been reported. The clinical significance, however, is mostly unclear. The aim of this study was to investigate the clinical relevance of Scedosporium spp. and Exophiala dermatitidis from sputum samples of patients with CF in the Netherlands. In this cross-sectional study, all CF patients of the Dutch national CF registry who were treated at five of the seven recognized CF centers during a 3-year period were included. We linked clinical data of the national CF registry with the national Dutch filamentous fungal database. We investigated the association between clinical characteristics and a positive sputum sample for Scedosporium spp. and E. dermatitidis, using logistic regression. Positive cultures for fungi were obtained from 3787 sputum samples from 699 of the 1312 patients with CF. Scedosporium spp. was associated with severe genotype, CF-related diabetes, several microorganisms, and inhaled antibiotics. E. dermatitidis was associated with older age, female sex, and Aspergillus spp. CF patients with and without Scedosporium spp. or E. dermatitidis seemed comparable in body mass index and lung function. This study suggests that Scedosporium spp. and E. dermatitidis are probably no major pathogens in CF patients in the Netherlands. Greater understanding of epidemiologic trends, risk factors, and pathogenicity of filamentous fungi in the respiratory tracts of patients with CF is needed.
Phase I trial of dimethyl fumarate, temozolomide, and radiation therapy in glioblastoma
Authors: Shafer Danielle , Tombes Mary Beth , Shrader Ellen , Ryan Alison , Bandyopadhyay Dipankar , Dent Paul , Malkin Mark 
Published: January 2020

Abstract

Background
Dimethyl fumarate (DMF), an oral agent approved for the treatment of relapsing–remitting multiple sclerosis (RRMS), has promising preclinical activity against glioblastoma (GBM). This phase I study sought to determine the recommended phase 2 dose (RP2D) of DMF and evaluate its safety and toxicity when combined with standard concurrent radiotherapy (RT) and temozolomide (TMZ) followed by maintenance TMZ in patients with newly diagnosed GBM.

Methods
Using a standard 3 + 3 dose-escalation design with 3 dose levels, patients received daily DMF with 60 Gy RT and concurrent TMZ 75 mg/m2 daily, followed by maintenance DMF (continuously) and TMZ 150–200 mg/m2 on days 1–5 of each 28-day cycle for up to 6 cycles. The maximum tolerated dose (MTD) was determined by evaluation of dose-limiting toxicity (DLT) during the first 6 weeks of therapy.

Results
Twelve patients were treated at the 3 dose levels, and no DLTs were observed. There were no unexpected toxicities. The most common grade 3/4 treatment related adverse events (AEs) were lymphopenia (58%), decreased CD4 count (17%), and thrombocytopenia (17%). Four patients completed all planned treatment; seven patients had progression on treatment. One patient chose to withdraw from the study during maintenance. The median progression-free survival (PFS) for all patients was 8.7 months with no difference in PFS between those with stable disease or a partial response; median overall survival was 13.8 months.

Conclusions
DMF may be safely combined with RT and TMZ in patients with newly diagnosed GBM. The RP2D for DMF is 240 mg three times daily.
The Future of Phage: Ethical Challenges of Using Phage Therapy to Treat Bacterial Infections
Authors: Anomaly Jonathan 
Published: January 2020

Abstract
For over a century, scientists have run experiments using phage viruses to treat bacterial infections. Until recently, the results were inconclusive because the mechanisms viruses use to attack bacteria were poorly understood. With the development of molecular biology, scientists now have a better sense of how phage work, and how they can be used to target infections. As resistance to traditional antibiotics continues to spread around the world, there is a moral imperative to facilitate research into phage therapy as an alternative treatment. This essay reviews ethical questions raised by phage therapy, and discusses regulatory challenges associated with phage research, and phage treatments.
Stepping After Stroke: Walking Characteristics in People With Chronic Stroke Differ on the Basis of Walking Speed, Walking Endurance, and Daily Steps
Authors: Handlery Reed , Fulk George , Pellegrini Christine , Stewart Jill Campbell , Monroe Courtney , Fritz Stacy 
Published: January 2020

Abstract

Background
What contributes to free-living walking after stroke is poorly understood. Studying the characteristics of walking may provide further details that guide interventions.

Objective
The objectives of this study were to examine how the walking characteristics of bouts per day, median steps per bout, maximum steps per bout, and time spent walking differ in individuals with various walking speeds, walking endurance, and daily steps and to identify cutoffs for differentiating ambulators who were active versus inactive.

Design
This study involved a cross-sectional analysis of data from the Locomotor Experience Applied Post-Stroke trial.

Methods
Participants were categorized by walking speed, walking endurance (via the 6-minute walk test), and daily steps (via 2 consecutive days of objective activity monitoring). Differences in walking characteristics were assessed. Linear regression determined which characteristics predicted daily step counts. Receiver operating characteristic curves and areas under the curve were used to determine which variable was most accurate in classifying individuals who were active (≥5500 daily steps).

Results
This study included 252 participants with chronic stroke. Regardless of categorization by walking speed, walking endurance, or daily steps, household ambulators had significantly fewer bouts per day, steps per bout, and maximum steps per bout and spent less time walking compared with community ambulators. The areas under the curve for maximum steps per bout and bouts per day were 0.91 (95% confidence interval = 0.88 to 0.95) and 0.83 (95% confidence interval = 0.78 to 0.88), respectively, with cutoffs of 648 steps and 53 bouts being used to differentiate active and inactive ambulation.

Limitations
Activity monitoring occurred for only 2 days.

Conclusions
Walking characteristics differed based on walking speed, walking endurance, and daily steps. Differences in daily steps between household and community ambulators were largely due to shorter and fewer walking bouts. Assessing and targeting walking bouts may prove useful for increasing stepping after stroke.
HIGHER CORRELATIONS AND THE ALTERNATIVE HYPOTHESIS
Authors: Lagarias Jeffrey C , Rodgers Brad 
Published: January 2020

AbstractThe Alternative Hypothesis (AH) concerns a hypothetical and unlikely picture of how zeros of the Riemann zeta function are spaced, which one would like to rule out. In the Alternative Hypothesis, the renormalized distance between non-trivial zeros is supposed to always lie at a half integer. It is known that the Alternative Hypothesis is compatible with what is known about the pair correlation function of zeta zeros. We ask whether what is currently known about higher correlation functions of the zeros is sufficient to rule out the Alternative Hypothesis and show by construction of an explicit counterexample point process that it is not. A similar result was recently independently obtained by Tao, using slightly different methods. We also apply the ergodic theorem to this point process to show there exists a deterministic collection of points lying in $\tfrac{1}{2}\mathbb{Z}$, which satisfy the Alternative Hypothesis spacing, but mimic the local statistics that are currently known about zeros of the zeta function.
‘Hokclyff’ and the Will of William Hoton
Authors: Brown Peter 
Published: January 2020

Abstract
There are two surviving copies of La Male Regle by Thomas Hoccleve, a lively account of his dissolute life as a clerk of the Privy Seal. One is part of an autograph manuscript of Hoccleve’s works in the Huntington Library, the other an incomplete version in Canterbury Cathedral Archives. Reference to a third copy survives in the will of William Hoton, proved in 1447. As well as La Male Regle, Hoton bequeathed a letter of Pharaoh, a chronicle and statutes, together with a mazer and pious donations. This information, coupled with records of Hoton’s family members, his burial place and associates, produces a profile of William Hoton linking him with the law and the book trade, and possibly with Neville’s Inn, the London town house used by a noble family to whose members Hoccleve addressed some of his poems. Hoton’s will also leads to a second individual who owned La Male Regle—the person who received it as a bequest, the common attorney and citizen, John Mordon. Neither Hoton nor Mordon has hitherto featured in discussions of the reception of the poem, which enjoyed a wider circulation than previously thought.
Silver(I) metallodrugs of thiosemicarbazones and naproxen: biocompatibility, in vitro anti-proliferative activity and in silico interaction studies with EGFR, VEGFR2 and LOX receptors
Authors: Bharathi Sundaram , Mahendiran Dharmasivam , Kumar Raju Senthil , Choi Hyo Jeong , Gajendiran Mani , Kim Kyobum , Rahiman Aziz Kalilur 
Published: January 2020

AbstractFour new heteroleptic silver(I) complexes with the general formula [Ag(L1–4)(nap)] (1–4), where L1–4 = 2-(1-(4-substitutedphenyl)ethylidene)hydrazinecarbothioamide and nap = naproxen, have been synthesized and characterized. The geometric parameters determined from density functional theory and UV-Vis studies indicate distorted tetrahedral geometry around silver(I) ion. Fourier transform infrared (FT IR) spectra evidenced asymmetric bidentate coordination mode of carboxyl oxygen atoms of naproxen with silver(I) ion. The complexes are stable for 72 h and biocompatibility was analysed towards normal human dermal fibroblast cells, which showed non-toxic nature up to 100 ng/ml. In vitro anti-proliferative activity of the complexes by MTT assay was tested against three human cancerous cell lines and one non-tumorigenic human breast epithelial cell line (MCF-10a) in which the complex 4 exhibited enhanced activity. The morphological changes observed by acridine orange/ethidium bromide and Hoechst 33258 staining method reveal apoptosis-inducing ability of the complexes. The molecular docking studies suggest hydrogen bonding, hydrophobic and π-pair interactions with the active site of epidermal growth factor receptor, vascular endothelial growth factor receptor 2 and lipoxygenase receptors.
Unraveling virus relationships by structure-based phylogenetic classification
Authors: Ng Weng M , Stelfox Alice J , Bowden Thomas A 
Published: January 2020

Abstract
Delineation of the intricacies of protein function from macromolecular structure constitutes a continual obstacle in the study of cell and pathogen biology. Structure-based phylogenetic analysis has emerged as a powerful tool for addressing this challenge, allowing the detection and quantification of conserved architectural properties between proteins, including those with low or no detectable sequence homology. With a focus on viral protein structure, we highlight how a number of investigations have utilized this powerful method to infer common functionality and ancestry.
The Effects of Frequent Quizzing on Exam Scores in a Baccalaureate Nursing Course
Authors: Sartain Andrea F. , Wright Vivian H. 
Published: January 2020

Abstract
This study examined the relationship between the use of frequent quizzing and students’ examination scores in a fundamental-level baccalaureate nursing course. Four cohorts of students were utilized: two cohorts (n = 230) received only unit exams and a comprehensive final, whereas the other cohorts (n = 210) were given quizzes in addition to the unit exams and comprehensive final. Exam scores were analyzed to determine if there was improvement in scores once quizzing was implemented. Comparing the quizzing and control cohorts, quizzing was found to improve both unit (p < .001, ηp
2 = .039) and final (p < .001, ηp
2 = .046) exam scores.
Virginia NP scope of practice
Authors: Smith Shelly , Buchanan Holly , Cloutier Rachel 
Published: January 2020

Abstract:
During the 2018 state legislative session, Virginia's General Assembly approved legislation supporting a transitional licensing model for NPs with at least 5 years of full-time work equivalence in their certification area. This article outlines Virginia's case as an example for NP advocates who are planning scope-of-practice legislation in other states.
Efficacy of Nalbuphine as an Adjuvant to Ropivacaine in Ultrasound-guided Supraclavicular Brachial Block
Authors: Kalika Prakash , Xue Rui , Zheng Junwei , Xiao Yun , Zhen Ming , Ran Ran 
Published: January 2020

Background:
A brachial plexus block (BPB) provides anesthesia and analgesia with limited duration. Various opioids have been used as adjuvants of local anesthetics to improve the effects.

Objective:
The objective of this study was to evaluate the safety and effectiveness of nalbuphine used as an adjuvant to local anesthetic during the supraclavicular BPB.

Materials and Methods:
In this prospective, double-blinded, randomized controlled study, 90 American Society of Anesthesiology (ASA) Physical Status I and II patients (aged 20 to 65 y) of either sex undergoing upper limb orthopedic surgeries under ultrasound-guided supraclavicular BPB were randomly allocated into 3 groups: group C (n=30), group NL (n=30), and group NH (n=30) for analyses. Each patient received 18 mL of 100 mg ropivacaine solution combined with 2 mL of normal saline, 2 mL of 10 mg nalbuphine, or 2 mL of 20 mg nalbuphine. The time of onset and block duration of sensory block (SB) and motor block (MB), duration of analgesia, hemodynamic variables, and any adverse effects were assessed.

Results:
Compared with group C, the onset time of both SB and MB were significantly shortened. The SB and MB duration were significantly prolonged in group NL and group NH. There was no significant difference between the duration of analgesia in group NL and NH although the analgesia duration of both groups was longer than group C. But the incidence of side effects in group NH such as vomiting was significantly higher than group NL.

Conclusions:
Nalbuphine is an effective adjuvant to 0.5% ropivacaine in ultrasound-guided supraclavicular BPB. The dosage of 10 mg improves the quality of the anesthesia with less incidence of side effects.
Intrathecal Morphine and Pulmonary Complications after Arthroplasty in Patients with Obstructive Sleep Apnea
Authors: Bai Johnny W. , Singh Mandeep , Short Anthony , Bozak Didem , Chung Frances , Chan Vincent W. S. , Bhatia Anuj , Perlas Anahi 
Published: January 2020

Abstract

Background
Intrathecal morphine is commonly and effectively used for analgesia after joint arthroplasty, but has been associated with delayed respiratory depression. Patients with obstructive sleep apnea may be at higher risk of postoperative pulmonary complications. However, data is limited regarding the safety of intrathecal morphine in this population undergoing arthroplasty.

Methods
This retrospective cohort study aimed to determine the safety of intrathecal morphine in 1,326 patients with documented or suspected obstructive sleep apnea undergoing hip or knee arthroplasty. Chart review was performed to determine clinical characteristics, perioperative events, and postoperative outcomes. All patients received neuraxial anesthesia with low-dose (100 μg) intrathecal morphine (exposure) or without opioids (control). The primary outcome was any postoperative pulmonary complication including: (1) respiratory depression requiring naloxone; (2) pneumonia; (3) acute respiratory event requiring consultation with the critical care response team; (4) respiratory failure requiring intubation/mechanical ventilation; (5) unplanned admission to the intensive care unit for respiratory support; and (6) death from a respiratory cause. The authors hypothesized that intrathecal morphine would be associated with increased postoperative complications.

Results
In 1,326 patients, 1,042 (78.6%) received intrathecal morphine. The mean age of patients was 65 ± 9 yr and body mass index was 34.7 ± 7.0 kg/m2. Of 1,326 patients, 622 (46.9%) had suspected obstructive sleep apnea (Snoring, Tired, Observed, Pressure, Body Mass Index, Age, Neck size, Gender [STOP-Bang] score greater than 3), while 704 of 1,326 (53.1%) had documented polysomnographic diagnosis. Postoperatively, 20 of 1,322 (1.5%) patients experienced pulmonary complications, including 14 of 1,039 (1.3%) in the exposed and 6 of 283 (2.1%) in the control group (P = 0.345). Overall, there were 6 of 1 322 (0.5%) cases of respiratory depression, 18 of 1,322 (1.4%) respiratory events requiring critical care team consultation, and 4 of 1,322 (0.3%) unplanned intensive care unit admissions; these rates were similar between both groups. After adjustment for confounding, intrathecal morphine was not significantly associated with postoperative pulmonary complication (adjusted odds ratio, 0.60 [95% CI, 0.24 to 1.67]; P = 0.308).

Conclusions
Low-dose intrathecal morphine, in conjunction with multimodal analgesia, was not reliably associated with postoperative pulmonary complications in patients with obstructive sleep apnea undergoing joint arthroplasty.

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