bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain exposure of the ATM inhibitor AZD1390 in humans—a positron emission tomography study
Authors: Jucaite Aurelija , Stenkrona Per , Cselényi Zsolt , De Vita Serena , Buil-Bruna Nuria , Varnäs Katarina , Savage Alicia , Varrone Andrea , Johnström Peter , Schou Magnus , Davison Chris , Sykes Andy , Pilla Reddy Venkatesh , Hoch Matthias , Vazquez-Romero Ana , Moein Mohammad Mahdi , Halldin Christer , Merchant Melinda S , Pass Martin , Farde Lars 
Published: October 2020

Abstract

Background
The protein kinase ataxia telangiectasia mutated (ATM) mediates cellular response to DNA damage induced by radiation. ATM inhibition decreases DNA damage repair in tumor cells and affects tumor growth. AZD1390 is a novel, highly potent, selective ATM inhibitor designed to cross the blood–brain barrier (BBB) and currently evaluated with radiotherapy in a phase I study in patients with brain malignancies. In the present study, PET was used to measure brain exposure of 11C-labeled AZD1390 after intravenous (i.v.) bolus administration in healthy subjects with an intact BBB.

Methods
AZD1390 was radiolabeled with carbon-11 and a microdose (mean injected mass 1.21 µg) was injected in 8 male subjects (21–65 y). The radioactivity concentration of [11C]AZD1390 in brain was measured using a high-resolution PET system. Radioactivity in arterial blood was measured to obtain a metabolite corrected arterial input function for quantitative image analysis. Participants were monitored by laboratory examinations, vital signs, electrocardiogram, adverse events.

Results
The brain radioactivity concentration of [11C]AZD1390 was 0.64 SUV (standard uptake value) and reached maximum 1.00% of injected dose at Tmax[brain] of 21 min (time of maximum brain radioactivity concentration) after i.v. injection. The whole brain total distribution volume was 5.20 mL*cm−3. No adverse events related to [11C]AZD1390 were reported.

Conclusions
This study demonstrates that [11C]AZD1390 crosses the intact BBB and supports development of AZD1390 for the treatment of glioblastoma multiforme or other brain malignancies. Moreover, it illustrates the potential of PET microdosing in predicting and guiding dose range and schedule for subsequent clinical studies.
Inflation, market structure, and innovation-driven growth with distinct cash constraints
Authors: Huang Chien-Yu , Chang Juin-Jen , Ji Lei 
Published: October 2020

Abstract
This article explores the effects of monetary policy (inflation) in a Schumpeterian growth model with an endogenous market structure and distinct cash (or cash-in-advance, CIA) constraints on consumption, production, and two types of R&D investment—quality-improving and variety-expanding R&D. We show that the relationship between inflation and growth is negative if quality-improving R&D (incumbent) is subject to the CIA constraint, but positive if variety-expanding R&D (entrant) is subject to the CIA constraint. Inflation has no effect on growth as consumption or production is subject to the CIA constraint. In addition, the firm size may either increase or decrease in response to inflation depending on which type of R&D is constrained by cash. With all CIA constraints properly imposed, a likely scenario in our numerical analysis shows that a rise in inflation leads the growth rate to exhibit a decrease in the short run but an increase in the long run. Moreover, our welfare analysis shows that Friedman’s rule, in general, is not socially optimal.
Evaluation of Nasopharyngeal Swab Collection Techniques for Nucleic Acid Recovery and Participant Experience: Recommendations for COVID-19 Diagnostics
Authors: Kinloch Natalie N , Shahid Aniqa , Ritchie Gordon , Dong Winnie , Lawson Tanya , Montaner Julio S G , Romney Marc G , Stefanovic Aleksandra , Matic Nancy , Brumme Chanson J , Lowe Christopher F , Brumme Zabrina L , Leung Victor 
Published: October 2020

Abstract
Nasopharyngeal swabs are critical to the diagnosis of respiratory infections including coronavirus disease 2019, but collection techniques vary. We compared 2 recommended nasopharyngeal swab collection techniques in adult volunteers and found that swab rotation following nasopharyngeal contact did not recover additional nucleic acid (as measured by human DNA/RNA copy number). Rotation was also less tolerable for participants. Notably, both discomfort and nucleic acid recovery were significantly higher in Asian participants, consistent with nasal anatomy differences. Our results suggest that it is unnecessary to rotate the swab in place following contact with the nasopharynx and reveal that procedural discomfort levels can differ by ethnicity.
Survey of Physical Therapists’ Attitudes, Knowledge, and Behaviors Regarding Diagnostic Imaging
Authors: Rundell Sean D , Maitland Murray E , Manske Robert C , Beneck George J 
Published: October 2020

Abstract

Objective
The purpose of this study was to describe physical therapists’ attitudes, knowledge, and behaviors regarding the use of diagnostic imaging.

Methods
Physical therapists in the United States were recruited from July 2018 through May 2019 to complete a web-based, cross-sectional survey. Participants were asked about demographics, their perceived knowledge base and skills for recommending or ordering different imaging modalities, and their behaviors regarding diagnostic imaging. Descriptive statistics were used to characterize the participants’ demographics and responses to all questions. Chi-square tests were performed to compare responses by characteristics of survey participants and Wilcoxon signed-rank tests to compare levels of agreement.

Results
The mean age was 43 years, and of the 739 respondents, 58% (n = 417) were female. Ninety-two percent of respondents (n = 595) reported having recommended diagnostic imaging to another provider at least once. Only 11.6% (n = 75) reported having ever directly ordered diagnostic imaging. Participants’ attitudes about their knowledge base and skills for recommending or ordering plain radiographs were stronger compared with any other imaging modalities followed by magnetic resonance imaging (MRI) over other imaging techniques. Participants’ attitudes on recommending plain radiographs or MRI differed by professional education level, board-certification status, fellowship completion, and years since graduation.

Conclusion
It is common for physical therapists to recommend imaging, but few have directly ordered imaging. Most survey participants believed that they have an adequate knowledge base and skills for recommending and ordering plain radiographs and MRI.

Impact
These results can serve as a benchmark for future comparison as policies and educations evolve. Understanding physical therapists’ attitudes, knowledge, and use of diagnostic imaging is important to inform research, policy, and education.
DETERMINATION OF 226RA IN URINE USING TRIPLE QUADRUPOLE INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY
Authors: Xiao Ge , Liu Yongzhong , Jones Robert L 
Published: October 2020

Abstract
Measuring 226Ra in urine at low levels is critical for both biomonitoring and radiological emergency response. Here we report a new analytical method to quantify 226Ra, as developed and validated by a simple dilute-and-shoot procedure, followed by Inductively Coupled Plasma-triple quadrupole-mass spectrometry detection using ‘No Gas MS-MS’ mode. The method provides rapid and accurate results for 226Ra with a limit of detection (LOD) down to 0.007 ng/l (0.26 Bq/l). This LOD is well below the recommended action levels for 226Ra detection in children and pregnant women (C/P) set by the Clinical Decision Guide (NCRP Report #161). Results for 226Ra obtained by this method are within ±7.0% of the target values of standard reference materials spiked in the urine.
Evaluation of methane production manipulated by level of intake in growing cattle and corn oil in finishing cattle
Authors: Winders Tommy M , Boyd Bradley M , Hilscher F Henry , Stowell Rick R , Fernando Samodha C , Erickson Galen E 
Published: October 2020

Abstract
Growing crossbred steers [n = 80, initial body weight (BW) = 274 kg, SD = 21] were used to evaluate the effect of ad libitum and limit-fed intakes on methane (CH4) production. Two treatments with four pens per treatment (10 steers per pen) were evaluated in a randomized block designed experiment, with BW as a blocking factor. Treatments included feeding the same diet at ad libitum intake or limit fed at 75% of ad libitum intakes. Diet consisted of 45% alfalfa, 30% sorghum silage, 22% modified distillers grains plus solubles, and supplement at 3% on a dry matter (DM) basis. This trial was followed by a finishing trial (n = 80; initial BW = 369 kg; SD = 25) to evaluate the effects of dietary corn oil on CH4 production. Two treatments with four pens per treatment (10 steers per pen) were used in a randomized complete block designed experiment. Cattle were rerandomized and blocked by BW within the previous treatment. Treatments consisted of a control diet (CON) containing 66% corn, 15% wet distillers grains plus solubles, 15% corn silage, and 4% supplement (DM basis). Corn oil treatment (OIL) displaced 3% corn by adding corn oil. Methane was collected in two pen-scale chambers by collecting air samples continuously from pens by rotating every 6 min with an ambient sample taken between pen measurements. Steers fed ad libitum had greater DM intake (DMI) by design and greater average daily gain (ADG; P &lt; 0.01) compared to limit-fed cattle; however, feed efficiency was not different between treatments (P = 0.40). Cattle fed ad libitum produced 156 g/d of CH4, which was greater (P &lt; 0.01) than limit-fed cattle (126 g per steer daily). In the finishing trial, BW, gains, and carcass traits were not impacted by treatment (P ≥ 0.14). Feed efficiency (P = 0.02) improved because intakes decreased (P = 0.02) by feeding OIL compared to CON. Daily CH4 production was less (P = 0.03) for OIL-fed cattle (115 g per steer daily) compared to CON-fed cattle (132 g per steer daily). Methane was reduced (P &lt; 0.01) by 17% for OIL-fed cattle compared to CON-fed cattle when expressed as grams of CH4 per kilogram of ADG. Feeding corn oil at 3% of diet DM reduced enteric CH4 production (grams per day) by 15%, which was only partially explained by a 3% decrease in DMI. Overall, a decrease in CH4 was observed when intake is limited in growing cattle and when corn oil is added in finishing diets.
Participation of Ghanaian pregnant women in an antimalarial drug trial: willingness, experiences and perceptions
Authors: Osarfo Joseph , Adjei Rose O , Magnussen Pascal , Tagbor Harry K 
Published: October 2020

Abstract

Background
With increasing orientation towards including pregnant women in clinical trials, investigators must conduct culturally acceptable research to aid recruitment and retention. There is limited information on experiences and meanings that pregnant women make of trial participation in Africa. This study reports experiences and perceptions of Ghanaian pregnant women regarding their participation in a clinical trial.

Methods
From October to December 2012, 45 in-depth interviews were conducted among pregnant women and their male partners regarding their experiences and perceptions of clinical trial processes as part of an antimalarial drug safety and efficacy trial in pregnant women in the Ashanti region of Ghana. Analysis was by predetermined themes and inductive analysis.

Results
Familiarity with the disease studied in the trial and trust in health workers favoured participation with the latter underlying acceptance of study drugs in the absence of symptoms. Adverse drug events were perceived as intrinsic sickness exhibited on the path to wellness. There were no cultural barriers to blood sampling during home visits but hospital-based sampling was preferred. Home visits were linked to participants having HIV infection.

Conclusion
This study contributes knowledge on sociocultural matters underpinning pregnant women's decisions regarding trial participation in an era of increasing drug trials involving pregnant women.
Using Medical Big Data to Develop Personalized Medicine for Dry Eye Disease
Authors: Inomata Takenori , Sung Jaemyoung , Nakamura Masahiro , Iwagami Masao , Okumura Yuichi , Iwata Nanami , Midorikawa-Inomata Akie , Fujimoto Keiichi , Eguchi Atsuko , Nagino Ken , Fujio Kenta , Miura Maria , Shokirova Hurramhon , Murakami Akira 
Published: October 2020

Abstract:
Dry eye disease (DED) is a chronic, multifactorial ocular surface disorder with multiple etiologies that results in tear film instability. Globally, the prevalence of DED is expected to increase with an aging society and daily use of digital devices. Unfortunately, the medical field is currently unprepared to meet the medical needs of patients with DED. Noninvasive, reliable, and readily reproducible biomarkers have not yet been identified, and the current mainstay treatment for DED relies on symptom alleviation using eye drops with no effective preventative therapies available. Medical big data analyses, mining information from multiomics studies and mobile health applications, may offer a solution for managing chronic conditions such as DED. Omics-based data on individual physiologic status may be leveraged to prevent high-risk diseases, accurately diagnose illness, and improve patient prognosis. Mobile health applications enable the portable collection of real-world medical data and biosignals through personal devices. Together, these data lay a robust foundation for personalized treatments for various ocular surface diseases and other pathologies that currently lack the components of precision medicine. To fully implement personalized and precision medicine, traditional aggregate medical data should not be applied directly to individuals without adjustments for personal etiology, phenotype, presentation, and symptoms.
Cost-utility Analysis of Rotavirus Vaccines Including the Latest Evidence and Data as of June 2020 in Japan
Authors: Kurosawa Teruyoshi , Watanabe Hiroshi , Takahashi Kenzo 
Published: October 2020

Background:
In several health economic analyses of rotavirus vaccines in Japan, all were not cost-effective from the healthcare payer perspective (HPP) but generally cost-effective from the societal perspective (SP). However, few studies have incorporated clinically significant factors of vaccine herd immunity, convulsions with gastroenteritis, encephalopathies, nosocomial infections, death, and intussusception as a vaccine side effect. A cost-utility analysis incorporating these were conducted.

Methods:
We used Bakir’s decision-tree model and data in Japan with 94% coverage rate, 5-year time horizon, and 2% discount. We compared the incremental cost-effectiveness ratio (ICER) with a willingness-to-pay of Japanese Yen (JPY) 5 million from HPP and SP. Scenario 1 examined items based on existing research; scenario 2 additionally examined the above-mentioned items. In scenario 2, break-even prices were determined, and one-way and probabilistic sensitivity analyses were performed.

Results:
In scenario 1, the ICER was JPY 6,057,281 from the HPP and dominant from the SP. In scenario 2, it was JPY 3,713,488 from the HPP. From the HPP in scenario 2, break-even prices were JPY 34,227 for an ICER of JPY 5 million and JPY 17,798 for cost-saving. One-way sensitivity analysis showed ICERs fluctuated widely with ambulatory visits and vaccination costs. In the probabilistic sensitivity analysis, ICERs of 54.8% were less than the willingness-to-pay. In scenario 2, from the SP, vaccines were dominant.

Conclusion:
From the HPP in scenario 2, the vaccines were cost-effective. In the sensitivity analyses, ICERs also improved from the HPP over previous studies. Herd immunity for ambulatory visits contributed most to the decline.
Unintended consequences of COVID-19 safety measures on patients with chronic knee pain forced to defer joint replacement surgery
Authors: Cisternas Alvaro F. , Ramachandran Roshni , Yaksh Tony L. , Nahama Alexis 
Published: October 2020

AbstractIn recent months, with the emergence of the COVID-19 pandemic, the American College of Surgeons and the U.S. Centers for Disease Control and Prevention officially recommended the delay of nonemergency procedures until the public health crisis is resolved. Deferring elective joint replacement surgeries for an unknown period is likely to decrease the incidence of infection with SARS-CoV-2 but is likely to have detrimental effects in individuals suffering from chronic knee pain. These detrimental effects extend beyond the discomfort of osteoarthritis (OA) and the inconvenience of rescheduling surgery. Disabling pain is a driving factor for individuals to seek medical intervention, including pharmacological palliative treatment and surgical procedures. The need for surgical intervention due to chronic pain as for knee and hip replacement is now put on hold indefinitely because access to surgical care has been limited. Although a moderate delay in surgical intervention may not produce a significant progression of OA within the knee, it could lead to muscle wasting due to immobility and exacerbate comorbidities, making rehabilitation more challenging. Importantly, it will have an impact on comorbidities driven by OA severity, notably decreased quality of life and depression. These patients with unremitting pain become increasingly susceptible to substance use disorders including opioids, alcohol, as well as prescription and illegal drugs. Appreciation of this downstream crisis created by delayed surgical correction requires aggressive consideration of nonsurgical, nonopiate supported interventions to reduce the morbidity associated with these delays brought upon by the currently restricted access to joint repair.
Isolated Frontosphenoidal Craniosynostosis: The Alder Hey Experience and a Novel Algorithm to Aid Diagnosis
Authors: Hennedige Anusha , Bridle Robyn , Richardson David , Duncan Christian , Parks Christopher , Sinha Ajay , Ellenbogen Jonathan 
Published: October 2020

Abstract
Unilateral synostotic frontal plagiocephaly is most commonly due to a premature fusion of the frontoparietal suture. However, the coronal ring comprises of major and minor sutures and these sutures in isolation or in combination can result in similar clinical presentations which can make diagnosis challenging and result in a delay in referral to a craniofacial surgeon for timely management. Isolated frontosphenoidal craniosynostosis is a rare clinical entity with only 49 cases reported in the English literature to date. The authors present our series of 4 patients to add to this cohort of patients and describe key characteristics to distinguish frontoparietal from isolated frontosphenoidal synostosis and introduce a means of differentiating these 2 diagnoses from posterior deformational plagiocephaly and unilateral lambdoid synostosis. All previous case reports have been diagnosed after radiological imaging but the authors have devised a novel algorithm to aid the clinician in diagnosis of craniosynostosis before any radiological imaging.
Flavobacterium salmonis sp. nov. isolated from Atlantic salmon (Salmo salar) and formal proposal to reclassify Flavobacterium spartansii as a later heterotypic synonym of Flavobacterium tructae
Authors: Kämpfer Peter , Irgang Rute , Glaeser Stefanie P. , Busse Hans-Jürgen , Criscuolo Alexis , Clermont Dominique , Avendaño-Herrera Ruben 
Published: October 2020

A Gram-staining-negative non endospore-forming strain, T13(2019)T was isolated from water samples from Atlantic salmon (Salmo salar) fry culture in Chile and studied in detail for its taxonomic position. The isolate shared highest 16S rRNA gene sequence similarities with the type strains of

Flavobacterium chungangense

(98.44 %) followed by

Flavobacterium tructae

and

Flavobacterium spartansii

(both 98.22 %). Menaquinone MK-6 was the predominant respiratory quinone in T13(2019)T. Major polar lipids were phosphatidylethanolamine, an ornithine lipid and the unidentified polar lipids L1, L3 and L4 lacking a functional group. The major polyamine was sym-homospermidine. The fatty acid profile contained major amounts of iso-C15 : 0, iso-C15 : 0 3-OH, iso-C17 : 0 3-OH, C15 : 0, summed feature 3 (C16 : 1
ω7c and/or iso-C15 : 0 2-OH) and various hydroxylated fatty acids in smaller amounts, among them iso-C16 : 0 3-OH, and C15 : 0 3-OH, which supported the grouping of the isolate into the genus

Flavobacterium

. Physiological/biochemical characterisation and ANI calculations with the type strains of the most closely related species allowed a clear phenotypic and genotypic differentiation. In addition it became obvious, that the type strains of

F. tructae

and

F. spartansii

showed 100 % 16S rRNA gene sequence similarities and ANI values of 97.21%/ 97.59 % and DDH values of 80.40 % [77.5 and 83%]. These data indicate that

F. tructae

and

F. spartansii

belong to the same species and it is proposed that

F. spartansii

is a later heterotypic synonym of

F. tructae

. For strain T13(2019)T (=CIP 111411T=LMG 30298T=CCM 8798T) a new species with the name Flavobacterium salmonis sp. nov. is proposed.
The link between CS gas exposure and menstrual cycle issues among female Yellow Vest protesters in France
Authors: Mahfud Yara , Samuel Alexander , Çelebi Elif , Adam-Troian Jais 
Published: October 2020

AbstractCS teargas is one of the most used tools for crowd-control worldwide. Exposure to CS teargas is known to have consequences on protesters’ health (i.e. eye, skin irritation, respiratory problems), but recent concerns have been raised over its potential gender-specific effects. Indeed, field and clinical observations report cases of menstrual cycle issues among female protesters following high exposure to teargas. The hypothesis of a link between teargas exposure and menstrual cycle issues is plausible from a physiological standpoint, but has not yet been empirically investigated. Using data from a cross-sectional study on Yellow Vests protesters’ health in France, we examined the relationship between exposure to teargas and menstrual cycle issues among female protesters (n = 145). Analyses suggested a positive link between exposure and menstrual cycle perturbations. These results constitute first and preliminary evidence that CS teargas may be linked with menstrual cycle among women, which need corroboration given the importance of this issue. We call for further research on the potential effects of CS teargas on women’s reproductive system.
COVID-CT-Mask-Net: Prediction of COVID-19 from CT Scans Using Regional Features
Authors: Ter-Sarkisov Aram 
Published: October 2020

AbstractWe present COVID-CT-Mask-Net model that predicts COVID-19 from CT scans. The model works in two stages: first, it detects the instances of ground glass opacity and consolidation in CT scans, then predicts the condition from the ranked bounding box detections. To develop the solution for the three-class problem (COVID, common pneumonia and control), we used the COVIDx-CT dataset derived from the dataset of CT scans collected by China National Center for Bioinformation. We use about 5% of the training split of COVIDx-CT to train the model, and without any complicated data normalization, balancing and regularization, and training only a small fraction of the model’s parameters, we achieve a 90.80% COVID sensitivity, 91.62% common pneumonia sensitivity and 92.10% normal sensitivity, and an overall accuracy of 91.66% on the test data (21182 images), bringing the ratio of test/train data to 7.06, which implies a very high capacity of the model to generalize to new data. We also establish an important result, that ranked regional predictions (bounding boxes with scores) in Mask R-CNN can be used to make accurate predictions of the image class. The full source code, models and pretrained weights are available on https://github.com/AlexTS1980/COVID-CT-Mask-Net.