bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic test interpretation and referral delay in patients with interstitial lung disease
Authors: Pritchard David , Adegunsoye Ayodeji , Lafond Elyse , Pugashetti Janelle Vu , DiGeronimo Ryan , Boctor Noelle , Sarma Nandini , Pan Isabella , Strek Mary , Kadoch Michael , Chung Jonathan H. , Oldham Justin M. 
Published: November 2019

Abstract

Background
Diagnostic delays are common in patients with interstitial lung disease (ILD). A substantial percentage of patients experience a diagnostic delay in the primary care setting, but the factors underpinning this observation remain unclear. In this multi-center investigation, we assessed ILD reporting on diagnostic test interpretation and its association with subsequent pulmonology referral by a primary care physician (PCP).

Methods
A retrospective cohort analysis of patients referred to the ILD programs at UC-Davis and University of Chicago by a PCP within each institution was performed. Computed tomography (CT) of the chest and abdomen and pulmonary function test (PFT) were reviewed to identify the date ILD features were first present and determine the time from diagnostic test to pulmonology referral. The association between ILD reporting on diagnostic test interpretation and pulmonology referral was assessed, as was the association between years of diagnostic delay and changes in fibrotic features on longitudinal chest CT.

Results
One hundred and forty-six patients were included in the final analysis. Prior to pulmonology referral, 66% (n = 97) of patients underwent chest CT, 15% (n = 21) underwent PFT and 15% (n = 21) underwent abdominal CT. ILD features were reported on 84, 62 and 33% of chest CT, PFT and abdominal CT interpretations, respectively. ILD reporting was associated with shorter time to pulmonology referral when undergoing chest CT (1.3 vs 15.1 months, respectively; p = 0.02), but not PFT or abdominal CT. ILD reporting was associated with increased likelihood of pulmonology referral within 6 months of diagnostic test when undergoing chest CT (rate ratio 2.17, 95% CI 1.03–4.56; p = 0.04), but not PFT or abdominal CT. Each year of diagnostic delay was associated with a 1.8% increase in percent fibrosis on chest CT. Patients with documented dyspnea had shorter time to chest CT acquisition and pulmonology referral than patients with documented cough and lung crackles.

Conclusions
Determinants of ILD diagnostic delays in the primary care setting include underreporting of ILD features on diagnostic testing and prolonged time to pulmonology referral even when ILD is reported. Interventions to modulate these factors may reduce ILD diagnostic delays in the primary care setting.
The matrikine acetyl-proline-glycine-proline and clinical features of COPD: findings from SPIROMICS
Authors:   for the SPIROMICS Investigators,, Wells J. Michael , Xing Dongqi , Viera Liliana , Burkes Robert M. , Wu Yixin , Bhatt Surya P. , Dransfield Mark T. , Couper David J. , O’Neal Wanda , Hoffman Eric A. , Gaggar Amit , Barjaktarevic Igor , Curtis Jeffrey L. , Labaki Wassim W. , Han Mei Lan K. , Freeman Christine M. , Putcha Nirupama , Schlange Thomas , Blalock J. Edwin 
Published: November 2019

Abstract

Background
Pulmonary and systemic inflammation are central features of chronic obstructive pulmonary disease (COPD). Previous studies have demonstrated relationships between biologically active extracellular matrix components, or matrikines, and COPD pathogenesis. We studied the relationships between the matrikine acetyl-proline-glycine-proline (AcPGP) in sputum and plasma and clinical features of COPD.

Methods
Sputum and plasma samples were obtained from COPD participants in the SPIROMICS cohort at enrollment. AcPGP was isolated using solid phase extraction and measured by mass spectrometry. Demographics, spirometry, quality of life questionnaires, and quantitative computed tomography (CT) imaging with parametric response mapping (PRM) were obtained at baseline. Severe COPD exacerbations were recorded at 1-year of prospective follow-up. We used linear and logistic regression models to measure associations between AcPGP and features of COPD, and Kaplan-Meier analyses to measure time-to-first severe exacerbation.

Results
The 182 COPD participants in the analysis were 66 ± 8 years old, 62% male, 84% White race, and 39% were current smokers. AcPGP concentrations were 0.61 ± 1.89 ng/mL (mean ± SD) in sputum and 0.60 ± 1.13 ng/mL in plasma. In adjusted linear regression models, sputum AcPGP was associated with FEV1/FVC, spirometric GOLD stage, PRM-small airways disease, and PRM-emphysema. Sputum AcPGP also correlated with severe AECOPD, and elevated sputum AcPGP was associated with shorter time-to-first severe COPD exacerbation. In contrast, plasma AcPGP was not associated with symptoms, pulmonary function, or severe exacerbation risk.

Conclusions
In COPD, sputum but not plasma AcPGP concentrations are associated with the severity of airflow limitation, small airways disease, emphysema, and risk for severe AECOPD at 1-year of follow-up.

Trial registration
ClinicalTrials.gov: NCT01969344 (SPIROMICS).
Repeated mosquito net distributions, improved treatment, and trends in malaria cases in sentinel health facilities in Papua New Guinea
Authors: Rodriguez-Rodriguez Daniela , Maraga Seri , Lorry Lina , Robinson Leanne J. , Siba Peter M. , Mueller Ivo , Pulford Justin , Ross Amanda , Hetzel Manuel W. 
Published: November 2019

AbstractBackgroundLong-lasting insecticidal nets (LLIN), improved diagnosis and artemisinin-based combination therapy (ACT) have reduced malaria prevalence in Papua New Guinea since 2008. Yet, national incidence trends are inconclusive due to confounding effects of the scale-up of rapid diagnostic tests, and inconsistencies in routine reporting.MethodsMalaria trends and their association with LLIN and ACT roll-out between 2010 and 2014 in seven sentinel health facilities were analysed. The analysis included 35,329 fever patients. Intervention effects were estimated using regression models.ResultsMalaria incidence initially ranged from 20 to 115/1000 population; subsequent trends varied by site. Overall, LLIN distributions had a cumulative effect, reducing the number of malaria cases with each round (incidence rate ratio ranging from 0.12 to 0.53 in five sites). No significant reduction was associated with ACT introduction.Plasmodium falciparumremained the dominant parasite in all sentinel health facilities. Resurgence occurred in one site in which a shift to early and outdoor biting of anophelines had previously been documented.ConclusionsLLINs, but not ACT, were associated with reductions of malaria cases in a range of settings, but sustainability of the gains appear to depend on local factors. Malaria programmes covering diverse transmission settings such as Papua New Guinea must consider local heterogeneity when choosing interventions and ensure continuous monitoring of trends.
Clinical implication of disturbed left atrial phasic functions in the heterogeneous population associated with hypertension or atrial fibrillation
Authors: Zhu Mengruo , Chen Haiyan , Liu Yang , Shu Xianhong 
Published: November 2019

Abstract

Background
To evaluate left atrial (LA) phasic functions in patients with hypertension and/or paroxysmal atrial fibrillation (PAF) and its clinical significance.

Methods
LA strain was studied in 77 patients (25 hypertension, 24 lone AF, and 28 with both hypertension and PAF) and 28 controls using two-dimensional speckle-tracking echocardiography (2D STE). The following indexes during atrial reservoir, conduit and pump phase were analyzed respectively: (1) peak atrial longitudinal strain (PALS) and strain rate (PALSR), (2) the standard deviation of time to PALS and PALSR of all LA segments (TpS-SD% and TpSR-SD%).

Results
Compared with controls, PALSres, PALScond and PALSRcond were significantly reduced in patients with isolated hypertension (all P < 0.01) but no significant differences were observed in PALSpump, PALSRpump and TpSpump-SD% between them (all P > 0.05). PALSpump, PALSRpump and PALSRres were significantly lower in patients with both hypertension and PAF than in those with isolated hypertension (all P < 0.05). PALS and PALSR were significantly decreased, and TpS-SD% was significantly increased during each phase in lone AF patients than in controls (all P < 0.05), and PALSRpump was further depressed in patients with both hypertension and PAF (P = 0.029). PALSRcond ≤ 1.475 s− 1 combined with TpSpump-SD% ≥ 3.25% (sensitivity, 85%; specificity, 71%; AUC = 0.845, P < 0.001) could distinguish lone AF from healthy subjects effectively, while in hypertensive patients, PALSpump ≤ 14.2% was found to be an independent differentiator for occurrence of AF or not with sensitivity of 81% and specificity of 84% (AUC = 0.838, P < 0.001). LAVI≥29.3 mL/m2 was an independent characteristic for reflecting different LA remodeling in lone AF or hypertension with AF.

Conclusions
The impairment of LA phasic functions was varied in patients with hypertension and/or AF. The disturbed LA phasic functions were proved to have independent abilities of differential diagnosis in this heterogeneous population associated with hypertension or AF.
Value of preoperative ultrasound in evaluating the peritoneal cancer index of pseudomyxoma peritonei
Authors: Liang Lei , Wang Wenhai , Zhou Nan , Guo Jun , Lu Yiyan , Xu Hongbin , Zhang Shutian 
Published: November 2019

AbstractPurposeThis study aimed to explore the value of preoperative ultrasonography (US) in evaluating the peritoneal cancer index (PCI) of pseudomyxoma peritonei (PMP).MethodsAn ultrasound examination was performed on 59 patients with PMP before surgery, and the ultrasound PCI was evaluated. The accuracy of ultrasound PCI score was evaluated with the surgical PCI score as the gold standard.ResultsThe preoperative ultrasound PCI was compared with the surgical PCI. The Spearman correlation coefficient of the total PCI score was 0.608 (P < 0.05). The difference in the Spearman correlation coefficient between the preoperative ultrasound PCI and the surgical PCI in areas 0–7 was statistically significant. (1) Among them, the total score and the correlation between 0–3 and 6 were higher. (2) Compared with the surgical PCI, overestimation (> 20%) was concentrated mainly in areas 2 and 4–8 for 2 points, and underestimation (< 20%) was concentrated mainly in areas 1, 3, 4, and 8 for 3 points. (3) The sensitivity and specificity of preoperative ultrasound for predicting the presence or absence of lesions were 85.7% and 50.0%, respectively. The sensitivity of LS 1, LS 2, and LS 3 was 31.7%, 48.2%, and 71.0%, respectively, and the specificity was 44.8%, 55.3%, and 58.8%, respectively.ConclusionThe ultrasound examination can be used to score the preoperative PCI, judge the severity, and predict the prognosis in patients with PMP.
Mouse-adapted H9N2 avian influenza virus causes systemic infection in mice
Authors: Hu Zhe , Zhang Yiran , Wang Zhen , Wang Jingjing , Tong Qi , Wang Mingyang , Sun Honglei , Pu Juan , Liu Changqing , Liu Jinhua , Sun Yipeng 
Published: November 2019

Abstract

Background
H9N2 influenza viruses continuously circulate in multiple avian species and are repeatedly transmitted to humans, posing a significant threat to public health. To investigate the adaptation ability of H9N2 avian influenza viruses (AIVs) to mammals and the mutations related to the host switch events, we serially passaged in mice two H9N2 viruses of different HA lineages — A/Quail/Hong Kong/G1/97 (G1) of the G1-like lineage and A/chicken/Shandong/ZB/2007 (ZB) of the BJ/94-like lineage —and generated two mouse-adapted H9N2 viruses (G1-MA and ZB-MA) that possessed significantly higher virulence than the wide-type viruses.

Finding
ZB-MA replicated systemically in mice. Genomic sequence alignment revealed 10 amino acid mutations coded by 4 different gene segments (PB2, PA, HA, and M) in G1-MA compared with the G1 virus and 23 amino acid mutations in 5 gene segments (PB1, PA, HA, M, and NS) in ZB-MA compared to ZB virus, indicating that the mutations in the polymerase, HA, M, and NS genes play critical roles in the adaptation of H9N2 AIVs to mammals, especially, the mutations of M1-Q198H and M1-A239T were shared in G1-MA and ZB-MA viruses. Additionally, several substitutions showed a higher frequency in human influenza viruses compared with avian viruses.

Conclusions
Different lineages of H9N2 could adapt well in mice and some viruses could gain the ability to replicate systemically and become neurovirulent. Thus, it is essential to pay attention to the mammalian adaptive evolution of the H9N2 virus.
Heparin sulfate is the attachment factor of duck Tembus virus on both BHK21 and DEF cells
Authors: Wu Shaoxiong , Wu Zhen , Wu Yuanyuan , Wang Tao , Wang Mingshu , Jia Renyong , Zhu Dekang , Liu Mafeng , Zhao Xinxin , Yang Qiao , Wu Ying , Zhang Shaqiu , Liu Yunya , Zhang Ling , Yu Yanling , Pan Leichang , Chen Shun , Cheng Anchun 
Published: November 2019

Abstract

Background
Duck tembusu virus (DTMUV, genus Flaviviruses, family Flaviviridae) is an emerging flavivirus that can infect a wide range of cells and cell lines in vitro, though the initial step of virus invasion remains obscure.

Methods
In this study, drug treatments that including heparin, chondroitin sulfate, heparinase I, chondroitinase ABC and trypsin were applied to detect the influence of DTMUV absorption, subsequently, the copy number of viral genome RNA was analyzed by quantitative real-time PCR. The inhibition process of viral absorption or entry by heparin was determined by western blotting, and the cytotoxicity of drug treated cells was detected by cell counting kit-8.

Results
We found that the desulfation of glycosaminoglycans (GAGs) with sodium chlorate had a significant effect on the adsorption of DTMUV in both BHK21 and DEF cells. Based on this result, we incubated cells with a mixture of DTMUV and GAGs competition inhibitors or pre-treated cells with inhibitors, after incubation with the virus, the NS5 expression of DTMUV and viral titers were detected. The data suggested that heparin can significantly inhibit the absorption of DTMUV in a dose dependent manner but not at the step of viral entry in BHK21 and DEF cells. Meanwhile, heparinase I can significantly inhibit DTMUV attachment step.

Conclusions
Our results clearly proved that heparin sulfate plays an important role in the first step of DTMUV entry, viral attachment, in both BHK21 and DEF cells, which sheds light on the entry mechanism of DTMUV.
Survival benefits of hypofractionated radiotherapy combined with temozolomide or temozolomide plus bevacizumab in elderly patients with glioblastoma aged ≥ 75 years
Authors: Ohno Makoto , Miyakita Yasuji , Takahashi Masamichi , Igaki Hiroshi , Matsushita Yuko , Ichimura Koichi , Narita Yoshitaka 
Published: November 2019

Abstract

Background and purpose
The purpose of this study was to evaluate the outcomes of elderly patients (aged ≥75 years) with newly diagnosed glioblastoma (GBM), who were treated with hypofractionated radiotherapy comprising 45 Gy in 15 fractions combined with temozolomide (TMZ) or TMZ and bevacizumab (TMZ/Bev).

Materials and methods
Between October 2007 and August 2018, 30 patients with GBM aged ≥75 years were treated with hypofractionated radiotherapy consisting of 45 Gy in 15 fractions. Twenty patients received TMZ and 10 received TMZ/Bev as upfront chemotherapy. O-6-methylguanine DNA methyltransferase (MGMT) promoter methylation status was analyzed by pyrosequencing. The cutoff value of the mean level of methylation at the 16 CpG sites was 16%.

Results
Median overall survival (OS) and progression-free survival (PFS) were 12.9 months and 9.9 months, respectively. The 1-year OS and PFS rates were 64.7 and 34.7%, respectively. Median OS and PFS did not differ significantly between patients with MGMT promoter hypermethylation (N = 11) and those with hypomethylation (N = 16) (17.4 vs. 11.8 months, p = 0.32; and 13.1 vs. 7.3 months, p = 0.11, respectively). The median OS and PFS were not significantly different between TMZ (N = 20) and TMZ/Bev (N = 10) chemotherapy (median OS: TMZ 12.9 months vs. TMZ/Bev 14.6 months, p = 0.93, median PFS: TMZ 8.5 months vs TMZ/Bev 10.0 months, p = 0.64, respectively). The median time until Karnofsky performance status (KPS) score decreasing below 60 points was 7.9 months. The best radiological responses included 11 patients with a partial response (36.7%). Grade 3/4 toxicities included leukopenia in 15 patients (50%), anorexia in 4 (13.3%), and hyponatremia during concomitant chemotherapy in 3 (10%).

Conclusion
Our hypofractionated radiotherapy regimen combined with TMZ or TMZ/Bev showed benefits in terms of OS, PFS, and KPS maintenance with acceptable toxicities in elderly patients with GBM aged ≥75 years.
Normofractionated stereotactic radiotherapy versus CyberKnife-based hypofractionation in skull base meningioma: a German and Italian pooled cohort analysis
Authors: Alfredo Conti , Carolin Senger , Güliz Acker , Anne Kluge , Antonio Pontoriero , Alberto Cacciola , Stefano Pergolizzi , Antonino Germanò , Harun Badakhshi , Markus Kufeld , Franziska Meinert , Phuong Nguyen , Franziska Loebel , Peter Vajkoczy , Volker Budach , David Kaul 
Published: November 2019

Abstract
Background
This retrospective German and Italian multicenter analysis aimed to compare the role of normofractionated stereotactic radiotherapy (nFSRT) to CyberKnife-based hypofractionated stereotactic radiotherapy (CK-hFSRT) for skull base meningiomas.

Methods
Overall, 341 patients across three centers were treated with either nFSRT or CK-hFSRT for skull base meningioma. Treatment planning was based on computed tomography (CT) and magnetic resonance imaging (MRI) following institutional guidelines. Most nFSRT patients received 33 × 1.8 Gy, and most CK-hFSRT patients received 5 × 5 Gy. The median follow-up time was 36 months (range: 1–232 months).

Results
In the CK-hFSRT group, the 1-, 3-, and 10-year local control (LC) rates were 99.4, 96.8, and 80.3%, respectively. In the nFSRT group, the 1-, 3-, and 10-year LC rates were 100, 99, and 79.1%, respectively. There were no significant differences in LC rates between the nFSRT and CK-hFSRT groups (p = 0.56, hazard ratio = 0.76, 95% confidence interval, 0.3–1.9). In the CK-hFSRT group, only one case (0.49%) of severe toxicity (CTCAE 4.0 ≥ 3) was observed. In the nFSRT group, three cases (2.1%) of grade III toxicity were observed.

Conclusion
This analysis of pooled data from three centers showed excellent LC and low side effect rates for patients treated with CK-hFSRT or nFSRT. The efficacy, safety, and convenience of a shortened treatment period provide a compelling case for the use of CK-hFSRT in patients with moderate size skull base meningioma and provided that OAR constraints are met.
Preliminary evaluation of autologous pericardium ring for tricuspid Annuloplasty: a two-year follow-up study
Authors: Jiang Wei , Long Xiao-Mao , Li Si-Cong , Zhong Yong-Long , He Bang-Fu , Lin Hui 
Published: November 2019

Abstract

Objective
To evaluate the effectiveness of autologous pericardium ring in tricuspid annuloplasty surgery for the treatment of tricuspid regurgitation (TR).

Methods
From December 2010 to December 2012, a total of 107 patients with secondary TR underwent tricuspid annuloplasty. The patients were divided into three groups: autologous pericardium ring group (n = 38), Edwards-MC3 ring group (n = 35), and DeVega group (n = 34). The patients were followed-up for two years. The survival rates and free from hospital readmission rates were measured and analyzed. The patients also received transthoracic echocardiography (TTE) in order to obtain TR regurgitant jet area to right atrial area (STR/STA), diastolic tricuspid annuloplasty diameter (DTAD), right atrial diameter (RAD), and right ventricular diameter (RVD).

Results
One patient from DeVega group and one patient from autologous pericardium ring died from low cardiac output syndrome during the perioperative period. In the two-year follow-up period, each group has one instance of death for unclear reasons. One month after operation, the STR/STA, DTAD, RAD, and RVD values in all groups were significantly lower than the pre-operation values (P < 0.05). During the two year follow-up period, DTAD values of patients from DeVega group increased significantly as compared to the values at one month post operation (P<0.05), which is different from the other two groups in which DTAD values remained stable (P>0.05). In both pericardium ring group and Edwards-MC3 group, STR/SRA, remained stable (P>0.05) during the follow-up period, whereas STR/SRA of the DeVega group had showed a tendency of increase (although statistically insignificant, P>0.05). There was no significant difference in the survival rates among three study groups (P > 0.05), but the rate of free from hospital readmission in the DeVega group was significantly lower than those in the other two groups (P < 0.05) during the two-year follow-up period.

Conclusions
Autologous pericardium tissue based ring annuloplasty demonstrated remarkable clinical utility for treating tricuspid regurgitation. It shows similar beneficial results to Edwards-MC3 annuloplasty within a short-term follow-up period, and outperforms the widely used DeVega annuloplasty. Autologous pericardium tissue annuloplasty represents a promising technique for tricuspid annuloplasty and holds great potential for treating tricuspid valve dysfunctions.
The attenuated end of the phenotypic spectrum in MPS III: from late-onset stable cognitive impairment to a non-neuronopathic phenotype
Authors: Nijmeijer Stephanie C. M. , van den Born L. Ingeborg , Kievit Anneke J. A. , Stepien Karolina M. , Langendonk Janneke , Marchal Jan Pieter , Roosing Susanne , Wijburg Frits A. , Wagenmakers Margreet A. E. M. 
Published: November 2019

Abstract

Background
The phenotypic spectrum of many rare disorders is much wider than previously considered. Mucopolysaccharidosis type III (Sanfilippo syndrome, MPS III), is a lysosomal storage disorder traditionally considered to be characterized by childhood onset, progressive neurocognitive deterioration with a rapidly or slowly progressing phenotype. The presented MPS III case series demonstrates adult onset phenotypes with mild cognitive impairment or non-neuronopathic phenotypes.

Methods
In this case series all adult MPS III patients with a mild- or non-neuronopathic phenotype, who attend the outpatient clinic of 3 expert centers for lysosomal storage disorders were included. A mild- or non-neuronopathic phenotype was defined as having completed regular secondary education and attaining a level of independency during adulthood, involving either independent living or a paid job.

Results
Twelve patients from six families, with a median age at diagnosis of 43 years (range 3–68) were included (11 MPS IIIA, 1 MPS IIIB). In the four index patients symptoms which led to diagnostic studies (whole exome sequencing and metabolomics) resulting in the diagnosis of MPS III; two patients presented with retinal dystrophy, one with hypertrophic cardiomyopathy and one with neurocognitive decline. The other eight patients were diagnosed by family screening. At a median age of 47 years (range 19–74) 9 out of the 12 patients had normal cognitive functions. Nine patients had retinal dystrophy and 8 patients hypertrophic cardiomyopathy.

Conclusion
We show the very mild end of the phenotypic spectrum of MPS III, ranging from late-onset stable neurocognitive impairment to a fully non-neuronopathic phenotype. Awareness of this phenotype could lead to timely diagnosis and genetic counseling.