bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lower maximum forces on oral structures when using gum-elastic bougie than when using endotracheal tube and stylet during both direct and indirect laryngoscopy by novices: a crossover study using a high-fidelity simulator
Authors: Ono Yuko , Shinohara Kazuaki , Shimada Jiro , Inoue Shigeaki , Kotani Joji 
Published: May 2020

Abstract
Background
Applying excessive force during endotracheal intubation (ETI) is associated with several complications, including dental trauma and hemodynamic alterations. A gum-elastic bougie (GEB), a type of tracheal tube introducer, is a useful airway adjunct for patients with poor laryngoscopic views. However, how the use of a GEB affects the force applied during laryngoscopy is unclear. We compared the force applied on the oral structures during ETI performed by novices using the GEB versus an endotracheal tube + stylet.

Methods
This prospective crossover study was conducted from April 2017 to March 2019 in a public medical university in Japan. In total, 209 medical students (4th and 5th grade, mean age of 23.7 ± 2.0 years) without clinical ETI experience were recruited. The participants used either a Macintosh direct laryngoscope (DL) or C-MAC video laryngoscope (VL) in combination with a GEB or stylet to perform ETI on a high-fidelity airway management simulator. The order of the first ETI method was randomized to minimize the learning curve effect. The outcomes of interest were the maximum forces applied on the maxillary incisors and tongue during laryngoscopy. The implanted sensors in the simulator quantified these forces automatically.

Results
The maximum force applied on the maxillary incisors was significantly lower when using a GEB than when using an endotracheal tube + stylet both with the Macintosh DL (39.0 ± 23.3 vs. 47.4 ± 32.6 N, P < 0.001) and C-MAC VL (38.9 ± 18.6 vs. 42.0 ± 22.1 N, P < 0.001). Similarly, the force applied on the tongue was significantly lower when using a GEB than when using an endotracheal tube + stylet both with the Macintosh DL (31.9 ± 20.8 vs. 37.8 ± 22.2 N, P < 0.001) and C-MAC VL (35.2 ± 17.5 vs. 38.4 ± 17.5 N, P < 0.001).

Conclusions
Compared with the use of an endotracheal tube + stylet, the use of a GEB was associated with lower maximum forces on the oral structures during both direct and indirect laryngoscopy performed by novices. Our results suggest the expanded role of a GEB beyond an airway adjunct for difficult airways.
Framing the numerical findings of Cochrane plain language summaries: two randomized controlled trials
Authors: Buljan Ivan , Tokalić Ružica , Roguljić Marija , Zakarija-Grković Irena , Vrdoljak Davorka , Milić Petra , Puljak Livia , Marušić Ana 
Published: May 2020

Abstract
Background
Cochrane systematic review Plain language Summaries (CSR PLSs should serve as a tool for the evidence translation to non-medical population. However, the evidence of optimal type of numerical presentation in CSR PLSs is still scarce. The aim of this study was to investigate readers’ comprehension and preferences for different presentation of findings, including framing and numerical data, in Cochrane systematic review Plain Language Summaries (CSR PLSs).

Methods
We conducted a parallel randomized trial and a crossover randomized trial at the School of Medicine and family practice offices in Split, Croatia. The participants were students and consumers. We assessed possible differences in comprehension, measured by four questions on PLS content, of CSR PLSs depending on the positive or negative framing of results (n = 91) (Trial 1) or using percentages or frequencies for the presentation of results (n = 245) (Trial 2). The outcome measures were comprehension of PLS content, perceived effectiveness of the treatment and readiness to use the treatment (all on 1–10 scales).

Results
In Trial 1 we found no difference in readers’ perception of the effectiveness of the described treatment, desire that the treatment be offered by their family doctor, readiness to use the treatment, or comprehension when CSR PLS results were presented positively or negatively. In Trial 2 we found no difference in CSR PLS comprehension when results were presented as natural frequencies or percentages (BF10 = 0.62, Bayesian t-test for independent samples).

Conclusions
Numerical presentation and framing direction of results appear to have no significant impact on understanding of messages in CSR PLSs.

Trial registration
The trials were registered in ClinicalTrials.gov. Protocol registration numbers: Trial 1: NCT03442387; Trial 2: NCT03554252.
Clinical features in primary care electronic records before diagnosis of ankylosing spondylitis: a nested case-control study
Authors: Bashir Mohammed T. , Iversen Lisa , Burton Christopher 
Published: May 2020

Abstract
Background
Ankylosing spondylitis (AS) often has a long period from first symptom presentation to diagnosis. We examined the occurrence of symptoms, prescriptions and diagnostic tests in primary care electronic records over time prior to a diagnosis of AS.

Methods
Nested case-control study using anonymised primary care electronic health records from Scotland. Cases were 74 adults with a first diagnosis of AS between 2000 and 2010. Controls were matched for age, sex and GP practice: (a) 296 randomly selected adults (b) 169 adults whose records contained codes indicating spinal conditions or symptoms.
We extracted clinical features (symptoms, AS-related disorders, prescriptions and diagnostic tests). Conditional logistic regression was used to examine the association between clinical features (both individually and in combinations) and diagnosis of AS. We examined the associations between clinical features and diagnosis over time prior to diagnosis.

Results
Several new composite pointers were predictive of AS: including distinct episodes of axial pain separated by more than 6 months (OR 12.7, 95% CI 4.7 to 34.6); the occurrence of axial pain with and tendon symptoms within the same year (OR 21.7, 95% CI 2.6 to 181.5); and the co-occurrence (within 30 days) of axial pain and a prescription for nonsteroidal anti-inflammatory drug (OR 10.4, 95%CI 4.9 to 22.1). Coded episodes of axial pain increased steadily over the 3 years before diagnosis. In contrast, large joint symptoms and enthesopathy showed little or no time trend prior to diagnosis.

Conclusions
We identified novel composite pointers to a diagnosis of AS in GP records. These may represent valuable targets for diagnostic support systems.
Lead poisoning; a neglected potential diagnosis in abdominal pain
Authors: Shabani Mahtab , Hadeiy Seyed Kaveh , Parhizgar Parinaz , Zamani Nasim , Mehrad Hamid , Hassanian-Moghaddam Hossein , Phillips Scott 
Published: May 2020

Abstract
Background
Abdominal pain may be a presenting symptom of lead poisoning and is often difficult to diagnose. This study aimed to determine the prevalence of abdominal pain in patients seen in the Laghman Hakim Hospital ED and GI clinic who were lead-intoxicated, with or without opiate use disorder.

Methods
Between July 2017 and January 2018, patients seen in the ED and GI clinic of Loghman Hakim Hospital with unexplained abdominal pain or abdominal pain resistant to treatment were enrolled. Informed consent was obtained from potential enrollees. For standardization, a pre-designed data collection tool was developed for uniform data acquisition. Opiate use was determined historically. For this study, lead poisoning was defined as a blood lead level (BLL) greater than or equal to 30 μg/dL (1.45 μmol/L) with concomitant GI symptoms.

Results
Of 125 patients admitted, 28 (22.4%) had BLLs higher than 30 μg/dL. None of the patients had signs and symptoms of opioid withdrawal syndrome during evaluation. Elevated BLLs were significantly correlated with oral opium use/abuse, history of addiction for over the preceding 12 years. The daily opium use was more than 2.75 g. There was a statistical correlation between lead toxicity and abdominal pain consistency and intensity, constipation, and paresthesias. Anemia, leukocytosis, and abnormal liver enzyme tests were laboratory findings associated with lead toxicity. Four patients died, one of whom was diagnosed with lead toxicity.

Conclusion
Lead toxicity should be considered in the potential differential diagnosis of severe and resistant abdominal pain in patients referring to general EDs or GI clinics if a positive history of opium abuse exists.
Exosomal miRNA signatures of pancreatic lesions
Authors: Vicentini Caterina , Calore Federica , Nigita Giovanni , Fadda Paolo , Simbolo Michele , Sperandio Nicola , Luchini Claudio , Lawlor Rita T. , Croce Carlo Maria , Corbo Vincenzo , Fassan Matteo , Scarpa Aldo 
Published: May 2020

Abstract
Background
Pancreatic and peri-pancreatic neoplasms encompass a variety of histotypes characterized by a heterogeneous prognostic impact. miRNAs are considered efficient candidate biomarkers due to their high stability in tissues and body fluids. We applied Nanostring profiling of circulating exosomal miRNAs to distinct pancreatic lesions in order to establish a source for biomarker development.

Methods
A series of 140 plasma samples obtained from patients affected by pancreatic ductal adenocarcinoma (PDAC, n = 58), pancreatic neuroendocrine tumors (PanNET, n = 42), intraductal papillary mucinous neoplasms (IPMN, n = 20), and ampulla of Vater carcinomas (AVC, n = 20) were analyzed. Comprehensive miRNA profiling was performed on plasma-derived exosomes. Relevant miRNAs were validated by qRT-PCR and in situ hybridization (ISH).

Results
Lesion specific miRNAs were identified through multiple disease comparisons. Selected miRNAs were validated in the plasma by qRT-PCR and at tissue level by ISH. We leveraged the presence of clinical subtypes with each disease cohort to identify miRNAs that are differentially enriched in aggressive phenotypes.

Conclusions
This study shows that pancreatic lesions are characterized by specific exosomal-miRNA signatures. We also provide the basis for further explorations in order to better understand the relevance of these signatures in pancreatic neoplasms.
Sensor-based characterization of daily walking: a new paradigm in pre-frailty/frailty assessment
Authors: Pradeep Kumar Danya , Toosizadeh Nima , Mohler Jane , Ehsani Hossein , Mannier Cassidy , Laksari Kaveh 
Published: May 2020

Abstract
Background
Frailty is a highly recognized geriatric syndrome resulting in decline in reserve across multiple physiological systems. Impaired physical function is one of the major indicators of frailty. The goal of this study was to evaluate an algorithm that discriminates between frailty groups (non-frail and pre-frail/frail) based on gait performance parameters derived from unsupervised daily physical activity (DPA).

Methods
DPA was acquired for 48 h from older adults (≥65 years) using a tri-axial accelerometer motion-sensor. Continuous bouts of walking for 20s, 30s, 40s, 50s and 60s without pauses were identified from acceleration data. These were then used to extract qualitative measures (gait variability, gait asymmetry, and gait irregularity) and quantitative measures (total continuous walking duration and maximum number of continuous steps) to characterize gait performance. Association between frailty and gait performance parameters was assessed using multinomial logistic models with frailty as the dependent variable, and gait performance parameters along with demographic parameters as independent variables.

Results
One hundred twenty-six older adults (44 non-frail, 60 pre-frail, and 22 frail, based on the Fried index) were recruited. Step- and stride-times, frequency domain gait variability, and continuous walking quantitative measures were significantly different between non-frail and pre-frail/frail groups (p < 0.05). Among the five different durations (20s, 30s, 40s, 50s and 60s), gait performance parameters extracted from 60s continuous walks provided the best frailty assessment results. Using the 60s gait performance parameters in the logistic model, pre-frail/frail group (vs. non-frail) was identified with 76.8% sensitivity and 80% specificity.

Discussion
Everyday walking characteristics were found to be associated with frailty. Along with quantitative measures of physical activity, qualitative measures are critical elements representing the early stages of frailty. In-home gait assessment offers an opportunity to screen for and monitor frailty.

Trial registration
The clinical trial was retrospectively registered on June 18th, 2013 with ClinicalTrials.gov, identifier NCT01880229.
Scrub typhus as a rare cause of acute pyelonephritis: case report
Authors: Bhattarai Tulsi , Poudel Sujan Chandra , Pokharel Nishma , Bhattarai Suraj 
Published: May 2020

Abstract
Background
Scrub typhus can present with atypical signs and symptoms such as those of acute kidney injury, gastroenteritis, pneumonitis, and acute respiratory distress syndrome. Meningitis, encephalitis, and hepatic dysfunction have also been reported, particularly in severe cases with multisystem involvement. Scrub typhus has never been reported in the literature to cause urinary tract infections (UTIs) which includes cystitis and pyelonephritis.

Case presentation
A 45-year old male presenting to the outpatient unit with fever, right flank pain, and burning micturition for three days was initially treated for UTI. However, he returned to the hospital on the fourth day of illness with persistent symptoms. He was hospitalized, with intravenous (IV) ceftriaxone. Computerized tomography scan of his abdomen-pelvis showed features of acute pyelonephritis, so his antibiotics were upgraded to meropenem and teicoplanin. Despite this, the patient’s condition deteriorated. Laboratory investigations showed multisystem involvement: decreasing platelets, raised creatinine, and deranged liver panel. As Kathmandu was hit by dengue epidemic during the patient’s hospitalization, on the seventh day of his illness, blood samples were sent for tropical fever investigation. All tests came out negative except for scrub typhus—IgM antibodies positive on rapid diagnostic test. The patient’s symptoms subsided after 48 h of starting doxycycline and he became fully asymptomatic four days later. Fever did not recur even after discontinuing other IV antibiotics, favoring scrub typhus disease rather than systemic bacterial sepsis.

Conclusions
Scrub typhus is an emerging infectious disease of Nepal. Therefore, every unexplained fever cases (irrespective of clinical presentation) should be evaluated for potential Rickettsiosis. Moreover, for cases with acute pyelonephritis, atypical causative agents should be investigated, for example scrub typhus in this case.
Concurrent pathogenic variants in SLC6A1/NOTCH1/PRIMPOL genes in a Chinese patient with myoclonic-atonic epilepsy, mild aortic valve stenosis and high myopia
Authors: Yuan Haiming , Wang Qingming , Li Yufeng , Cheng Shuangxi , Liu Jianxin , Liu Yanhui 
Published: May 2020

Abstract
Background
Pathogenic SLC6A1 variants have been reported in patients with myoclonic-atonic epilepsy (MAE). NOTCH1, encoding a member of the Notch family of proteins, is known to be associated with aortic valve disease. The PRIMPOL variant has only been identified in Chinese patients with high myopia. Exome sequencing analysis now allows the simultaneous detection of multiple genetic etiologies for patients with complicated clinical features. However, the presence of three Mendelian disorders in one patient supported by their respective pathogenic variants and clinical phenotypes is very rare.

Case presentation
Here, we report a 4-year-old Chinese boy who presented with MAE, delayed language, borderline intellectual disability (ID), mildly impaired social skills and attention deficit hyperactivity disorder (ADHD). He also had mild aortic valve stenosis and high myopia. Using whole-exome sequencing (WES), we identified three variants: (1) SLC6A1, NM_003042.4: c.881-883del (p.Phe294del), (2) NOTCH1, NM_017617.5:c.1100-2A > G and (3) PRIMPOL, NM_152683.4:c.265 T > G (p.Tyr89Asp). Parental Sanger sequencing confirmed that SLC6A1 and NOTCH1 variants were de novo, whereas the PRIMPOL variant was inherited from the father who also had high myopia. Furthermore, the PRIMPOL variant was absent from the genomes of the paternal grandparents, and thus was also a de novo event in the family. All three variants are classified as pathogenic.

Conclusion
The SLC6A1 variant could explain the features of MAE, delayed language, borderline ID, impaired social skills and ADHD in this patient, whereas the features of aortic valve stenosis and high myopia of the patient may be explained by variants in NOTCH1 and PRIMPOL, respectively. This case demonstrated the utility of exome sequencing in uncovering the multiple pathogenic variants in a patient with complicated phenotypes due to the blending of three Mendelian disorders.
Clinical validation of full genotyping CLART® HPV4S assay on SurePath and ThinPrep collected screening samples according to the international guidelines for human papillomavirus test requirements for cervical screening
Authors: Ejegod Ditte Møller , Lagheden Camilla , Bhatia Ramya , Pedersen Helle , Boada Elia Alcañiz , Sundström Karin , Cortés Javier , Josë F. Xavier Bosch , Cuschieri Kate , Dillner Joakim , Bonde Jesper 
Published: May 2020

Abstract
Background
To ensure the highest quality of human papillomavirus (HPV) testing in primary cervical cancer screening, novel HPV assays must be evaluated in accordance with the international guidelines. Furthermore, HPV assay with genotyping capabilities are becoming increasingly important in triage of HPV positive women in primary HPV screening. Here we evaluate a full genotyping HPV assay intended for primary screening.

Methods
The CLART® HPV4S (CLART4S) assay is a newly developed full-genotyping assay detecting 14 oncogenic (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68) and two non-oncogenic HPV genotypes (6, 11). It was evaluated using SurePath and ThinPrep screening samples collected from the Danish and Swedish cervical cancer screening programs, respectively. For calculation of sensitivity, 81 SurePath and 80 ThinPrep samples with confirmed ≥CIN2 were assessed. For clinical specificity analysis, 1184 SurePath and 1169 ThinPrep samples from women with <CIN2 histology were assessed. Sensitivity and specificity of the CLART4S assay was compared to an established reference test; the MGP-PCR (Modified General Primers GP5+/6+ with genotyping using Luminex). Inter and intra laboratory reproducibility of the assay was assessed using 540 SurePath and 520 ThinPrep samples, respectively. The genotype concordance between CLART4S and MGP-PCR was also assessed.

Results
In SurePath samples, the sensitivity of CLART4S was 0.90 (MGP-PCR =0.93) and the specificity was 0.91 (MGP-PCR = 0.91); In ThinPrep samples the sensitivity of CLART4S was 0.98 (MGP-PCR = 1.00) and specificity was 0.94 (MGP-PCR =0.87). The CLART4S was shown to be non-inferior to that of MGP-PCR for both sensitivity (p = 0.002; p = 0.01) and specificity (p = 0.01; p = 0.00) in SurePath and ThinPrep samples, respectively. Intra-laboratory reproducibility and inter-laboratory agreement was met for both media types. The individual genotype concordance between CLART4S and MGP-PCR was good agreement for almost all 14 HPV genotypes in both media types.

Conclusions
The CLART4S assay was proved non-inferior to the comparator assay MGP-PCR for both sensitivity and specificity using SurePath and ThinPrep cervical cancer screening samples from the Danish and Swedish screening programs, respectively. This is the first study to demonstrate clinical validation of a full-genotyping HPV assay conducted in parallel on both SurePath and ThinPrep collected samples.
Bis-benzylidine Piperidone RA190 treatment of hepatocellular carcinoma via binding RPN13 and inhibiting NF-κB signaling
Authors: Soong Ruey-Shyang , Anchoori Ravi K. , Roden Richard B. S. , Cho Rou-Ling , Chen Yi-Chan , Tseng Sheng-Chieh , Huang Yun-Li , Liao Po-Cheng , Shyu Yu-Chiau 
Published: May 2020

Abstract
Background
According to GLOBOSCAN, hepatocellular carcinoma (HCC) claimed 782,000 lives in 2018. The tyrosine kinase inhibitor sofafenib is used to treat HCC, but new anticancer agents targeting different pathways are urgently needed to improve outcomes for patients with advanced disease. The aberrant metabolism and aggressive growth of cancer cells can render them particularly susceptible to proteasome inhibition, as demonstrated by bortezomib treatment of multiple myeloma. However, resistance does emerge, and this 20S proteasome inhibitor has not proven active against HCC. The bis-benzylidine piperidone RA190 represents a novel class of proteasome inhibitor that covalently binds to cysteine 88 of RPN13, an ubiquitin receptor subunit of the proteasome’s 19S regulatory particle. RA190 treatment inhibits proteasome function, causing rapid accumulation of polyubiquitinated proteins. Considerable evidence suggests that nuclear factor κB (NF-κB) signaling, which is dependent upon the proteasome, is a major driver of inflammation-associated cancers, including HCC.

Methods
Human HCC cell lines were treated with titrations of RA190. The time course of endoplasmic reticulum stress and NF-κB-related mechanisms by which RA190 may trigger apoptosis were assessed. The therapeutic activity of RA190 was also determined in an orthotopic HCC xenograft mouse model.

Results
RA190 is toxic to HCC cells and synergizes with sofafenib. RA190 triggers rapid accumulation of polyubiquitinated proteins, unresolved endoplasmic reticulum stress, and cell death via apoptosis. RA190 blocks proteasomal degradation of IκBα and consequent release of NF-κB into the nuclei of HCC cells. Treatment of mice bearing an orthotopic HCC model with RA190 significantly reduced tumor growth.

Conclusions
RA190 has therapeutic activity in a xenograft model, and with sorafenib exhibited synergetic killing of HCC cells in vitro, suggesting further exploration of such a combination treatment of HCC is warranted.
Glistening formation in a new hydrophobic acrylic intraocular lens
Authors: Yildirim Timur M. , Fang Hui , Schickhardt Sonja K. , Wang Qiang , Merz Patrick R. , Auffarth Gerd U. 
Published: May 2020

Abstract
Background
The formation of fluid-filled microvacuoles, termed glistenings, is a common complication of intraocular lenses (IOLs) made from hydrophobic acrylate. Using our well-established in-vitro laboratory method, we evaluated a new IOL material’s resistance to glistening formation.

Methods
An in-vitro stress test for glistening induction was performed on 20 samples of hydrophobic acrylic IOLs: ten of the new Eyecryl ASHFY600 (Biotech Vision Care, Ahmedabad, India) compared with ten samples of AcrySof IQ SN60WF (Alcon, Fort Worth, USA). The number of microvacuoles per square millimetre (MV/mm2) was evaluated in five sections of each IOL. The results for each model were compared and rated on a modified Miyata Scale for grading glistening severity.

Results
In all cases, glistening number was higher in the central section of the IOL optic than in the periphery. Mean number of MV/mm2 was highest in the central part of the AcrySof IQ SN60WF, with 41.84 (±27.67) MVs/mm2. The lowest number of glistenings was found in the five sections of the Eyecryl ASHFY600 with 0.52 (±0.24) MVs/mm2. Mean value of the Eyecryl ASHFY600 IOL, using the Miyata Scale, was Zero.

Conclusion
In this in-vitro laboratory study, the new hydrophobic acrylic IOL showed a high resistance to microvacuole formation. Results from this in-vitro study suggest that glistening numbers will be low in clinical use in the Eyecryl ASHFY600.