bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated between behavior of administrating or recommending mumps vaccine and primary care physicians’ knowledge about vaccination: A nationwide cross‐sectional study in Japan
Authors: Takeuchi Jiro , Sakanishi Yuta , Okada Tadao , Nakayama Kuniko , Chiba Hiroshi , Suganaga Rei , Nishioka Yosuke , Kishi Tomomi , Suzuki Tomio ,   Preventive Medicine, Health Promotion Committee Vaccine Team, Japan Primary Care Association, Japan
Published: June 2021

Background

In Japan, the mumps‐containing vaccine was withdrawn from routine vaccination in 1993, and it became a voluntary vaccination. This study aimed to evaluate the association between the physicians’ knowledge about vaccinations and the administration or recommendation of the mumps vaccine.

Methods

We conducted a nationwide cross‐sectional study targeting primary care physicians (PCPs) in Japan. We used a web‐based self‐administered questionnaire by Preventive Medicine and Health Promotion Committee Vaccine Team, the Japan Primary Care Association (JPCA), from March to June in 2019. The outcome of the study was the association between PCPs’ knowledge about vaccine and the administration or recommendation of mumps vaccine. We obtained the information on background, subsidies of mumps vaccination for children from the local government, and vaccination quiz scores. We performed logistic regression analysis to estimate the odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Among 10,470 PCPs in JPCA, 5075 were excluded. We received responses from 1084 PCPs (20.1%) and enrolled 981 participants in the analysis. PCPs with a higher score on the vaccination quizzes were significantly more likely to administrate the mumps vaccine for adults (adjusted odds ratio [AOR] 1.93, 95% CI 1.45–2.59, p < 0.001) and recommend mumps vaccine to adults than PCPs with a lower score (AOR 1.78, 95% CI 1.33–2.40, p < 0.001).

Conclusions

We revealed an association between the administration or recommendation of mumps vaccine and PCPs’ better vaccination knowledge.
Down‐regulation of circITCH promotes osteosarcoma development and resistance to doxorubicin via the miR‐524/RASSF6 axis
Authors: Zhou Wei , Liu Yuan , Wu Xuejian
Published: June 2021

Background

Osteosarcoma (OS) is a malignant bone cancer, in which circular RNAs (circRNAs) act as important modulators. The present study aimed to explore the functional role of circRNA itchy E3 ubiquitin protein ligase (circITCH) in the development and doxorubicin (DXR) resistance of OS and the possible mechanistic pathway.

Methods

A quantitative real‐time polymerase chain reaction or western blot assays were exploited to analyze the expression of circITCH, miR‐524 and Ras association domain family member 6 (RASSF6). Cell viability and half‐maximal inhibitory concentration (IC50) value of DXR were monitored using a cell counting kit‐8 assay. Cell migration, invasion and apoptosis were determined via a transwell assay and flow cytometry. The target interaction among circITCH, miR‐524 and RASSF6 was validated by dual‐luciferase reporter and RNA immunoprecipitation assays. A xenograft model of MG‐63/DXR cells stably expressing circITCH in nude mice was established for assessing the role of circITCH in vivo.

Results

Down‐regulation of circITCH and RASSF6, as well as the up‐regulation of miR‐524, was revealed in OS by investigating 40 paired OS tissue and normal tissue samples. Overexpression of circITCH lowered the cell viability, IC50 value of DXR, migration and invasion, whereas it facilitated apoptosis of OS cells. circITCH sponged miR‐524 to up‐regulate RASSF6, causing OS progression inhibition and DXR resistance reduction. Additionally, circITCH up‐regulation reduced tumor growth in vivo.

Conclusions

Transduction with circITCH represses OS progression and promotes DXR sensitivity by the miR‐524/RASSF6 axis, providing a new perspective for therapeutic intervention.
Diverse Right Ventricular Remodeling Evaluated by MRI and Prognosis in Eisenmenger Syndrome With Different Shunt Locations
Authors: Gong Chao , He Shuai , Chen Xiaoling , Wang Lili , Guo Jiajuan , He Juan , Yin Lidan , Chen Chen , Han Yuchi , Chen Yucheng
Published: June 2021

Background

Congenital shunt location is related to Eisenmenger syndrome (ES) survival. Moreover, right ventricular (RV) remodeling is associated with poor survival in pulmonary hypertension.

Purpose

To investigate RV remodeling using comprehensive magnetic resonance imaging (MRI) techniques and identify its relationship with prognosis in ES subgroups classified by shunt location.

Study Type

Prospective observational study.

Population

Fifty‐four adults with ES (16 with pre‐tricuspid shunt and 38 with post‐tricuspid shunt).

Field Strength/Sequence

3.0 T/cine MRI with balanced steady‐state free precession sequence, late gadolinium enhancement with inversion recovery segmented gradient echo sequence and phase‐sensitive reconstruction, and T1 mapping with modified Look‐Locker inversion recovery sequence.

Assessment

Demographics, clinical characteristics, hemodynamics, RV remodeling features (morphology, systolic function, RV–pulmonary artery (PA) coupling and myocardial fibrosis), and prognosis were compared between ES subgroups. The adverse endpoint was all‐cause mortality or readmission for heart failure.

Statistical Tests

The independent samples t‐test, Fisher's exact test or Chi‐squared test, and the Kaplan–Meier method were used. P < 0.05 was considered significant.

Results

Compared to patients with post‐tricuspid shunt, patients with pre‐tricuspid shunt were significantly older and had higher N‐terminal pro‐B‐type natriuretic peptide concentrations and poorer exercise tolerance. Pre‐tricuspid shunt showed significantly larger RV dimensions (end‐diastolic volume index: 185.81 ± 37.49 vs. 98.20 ± 36.26 mL/m2), worse RV ejection fraction (23.54% ± 12.35% vs. 40.82% ± 10.77%), and RV–PA decoupling (0.35 ± 0.31 vs. 0.72 ± 0.29). Biventricular myocardial fibrosis was significantly more severe in pre‐tricuspid shunt than post‐tricuspid shunt (extracellular volume, left ventricle: 35.85% ± 2.58% vs. 29.10% ± 5.20%; RV free wall: 30.93% ± 5.65% vs. 26.75% ± 5.15%). In addition, pre‐tricuspid shunt demonstrated a significantly increased risk of adverse endpoint (hazard ratio: 2.938, 95% confidence interval: 1.204–7.172).

Data Conclusion

ES with pre‐tricuspid shunt might be a unique subtype with worse clinically decompensated RV remodeling and poor prognosis.

Level of Evidence: 2

Technical Efficacy Stage: 5
Factors affecting signal quality in implantable cardiac monitors with long sensing vector
Authors: Forleo Giovanni B. , Amellone Claudia , Sacchi Riccardo , Lombardi Leonida , Lucciola Maria Teresa , Scotti Valentina , Viecca Maurizio , Schiavone Marco , Giacopelli Daniele , Giammaria Massimo
Published: June 2021

Purpose

Electrical artefacts are frequent in implantable cardiac monitors (ICMs). We analyzed the subcutaneous electrogram (sECG) provided by an ICM with a long sensing vector and factors potentially affecting its quality.

Methods

Consecutive ICM recipients underwent a follow‐up where demographics, body mass index (BMI), implant location, and surface ECG were collected. The sECG was then analyzed in terms of R‐wave amplitude and P‐wave visibility.

Results

A total of 84 patients (43% female, median age 68 [58‐76] years) were enrolled at 3 sites. ICMs were positioned with intermediate inclination (n = 44, 52%), parallel (n = 35, 43%), or perpendicular (n = 5, 6%) to the sternum. The median R‐wave amplitude was 1.10 (0.72‐1.48) mV with P waves readily visible in 69.2% (95% confidence interval, CI: 57.8%‐79.2%), partially visible in 23.1% [95% CI: 14.3%‐34.0%], and never visible in 7.7% [95% CI: 2.9%‐16.0%] of patients. Men had higher R‐wave amplitudes compared to women (1.40 [0.96‐1.80] mV vs 1.00 [0.60‐1.20] mV, P = .001), while obese people tended to have lower values (0.80 [0.62‐1.28] mV vs 1.10 [0.90‐1.50] mV, P = .074). The P‐wave visibility reached 86.2% [95% CI: 68.3%‐96.1%] in patients with high‐voltage P waves (≥0.2 mV) at surface ECG. The sECG quality was not affected by implant site.

Conclusion

In ordinary clinical practice, ICMs with long sensing vector provided median R‐wave amplitude above 1 mV and reliable P‐wave visibility of nearly 70%, regardless of the position of the device. Women and obese patients showed lower but still very good signal quality.
Carbonate fluxes by coccolithophore species between NW Africa and the Caribbean: Implications for the biological carbon pump
Authors: Guerreiro Catarina V. , Baumann Karl‐Heinz , Brummer Geert‐Jan A. , Valente André , Fischer Gerhard , Ziveri Patrizia , Brotas Vanda , Stuut Jan‐Berend W.
Published: June 2021

Coccolithophores are among the most important calcifying pelagic organisms. To assess how coccolithophore species with different coccolith‐carbonate mass and distinct ecological resilience to ocean warming will influence the “rain ratio” and the “biological carbon pump”, 1 yr of species‐specific coccolith‐carbonate export fluxes were quantified using sediment traps moored at four sites between NW Africa and the Caribbean (i.e., CB‐20°N/21°W, at 1214 m; M1‐12°N/23°W, at 1150 m; M2‐14°N/37°W, at 1235 m; M4‐12°N/49°W, at 1130 m). Highest coccolith‐CaCO3 fluxes at the westernmost site M4, where the nutricline is deepest along the tropical North Atlantic, were dominated by deep‐dwelling small‐sized coccolith species Florisphaera profunda and Gladiolithus flabellatus. Total coccolith‐CaCO3 fluxes of 371 mg m−2 yr−1 at M4 were followed by 165 mg m−2 yr−1 at the north‐easternmost CB, 130 mg m−2 yr−1 at M1, and 114 mg m−2 yr−1 at M2 in between. Coccoliths accounted for nearly half of the total carbonate flux at M4 (45%), much higher compared to 23% at M2 and 15% at M1 and CB. At site M4, highest ratios of coccolith‐CaCO3 to particulate organic carbon fluxes and weak correlations between the carbonate of deep‐dwelling species and particulate organic carbon suggest that increasing productivity in the lower photic zone in response to ocean warming might enhance the rain ratio and reduce the coccolith‐ballasting efficiency. The resulting weakened biological carbon pump could, however, be counterbalanced by increasing frequency of Saharan dust outbreaks across the tropical Atlantic, providing mineral ballast as well as nutrients to fuel fast‐blooming and ballast‐efficient coccolithophore species.
Improving lifestyle obesity treatment during the COVID‐19 pandemic and beyond: New challenges for weight management
Authors: Caldwell Ann E. , Thomas Elizabeth A. , Rynders Corey , Holliman Brooke Dorsey , Perreira Cathryn , Ostendorf Danielle M. , Catenacci Victoria A.
Published: June 2021

Objective

The COVID‐19 pandemic has resulted in significant changes to daily life and many health‐related behaviors. The objective of this study was to examine how the stay‐at‐home/safer‐at‐home mandates issued in Colorado (March 2020–May 2020) impacted lifestyle behaviors and mental health among individuals with overweight or obesity participating in two separate behavioral weight loss trials (n = 82).

Methods

Questionnaires were used to collect qualitative and quantitative data on challenges to weight loss presented by the COVID‐19 pandemic, including changes in dietary intake, physical activity, sedentary behavior, and mental health during the stay‐at‐home/safer‐at‐home mandates.

Results

Using a convergent mixed method approach integrating qualitative and quantitative data, the greatest challenge experienced by participants was increased stress and anxiety, which led to more unhealthy behaviors. The majority perceived it to be harder to adhere to the prescribed diet (81%) and recommended physical activity (68%); however, self‐reported exercise on weekdays increased significantly and 92% of participants lost weight or maintained weight within ±1% 5–6 weeks following the stay‐at‐home mandate.

Conclusion

Study results suggest that obesity treatment programs should consider and attempt to address the burden of stress and anxiety stemming from the COVID‐19 pandemic and other sources due to the negative effects they can have on weight management and associated behaviors.
Human adipose tissue gene expression of solute carrier family 19 member 3 (SLC19A3); relation to obesity and weight‐loss
Authors: Pereira Maria J. , Andersson‐Assarsson Johanna C. , Jacobson Peter , Kamble Prasad , Taube Magdalena , Sjöholm Kajsa , Carlsson Lena M. S. , Svensson Per‐Arne
Published: June 2021

Objective

Adipose tissue is a specialized endocrine organ that is involved in modulating whole‐body energy homeostasis and expresses a specific subset of genes, which may play a role in adipose tissue metabolism. The aim of this study was to search for novel adipose tissue‐specific genes using a tissue panel of RNAseq expression profiles.

Methods

RNAseq expression profiles from 53 human tissues were downloaded from the GTex database. SLC19A3 expression was analyzed by microarray or real‐time PCR in two sets of paired subcutaneous and omental adipose tissue samples, in two studies with adipose tissue from persons with high or low body mass index (BMI), in adipose tissue from patients who underwent weight loss with a very‐low caloric diet and during preadipocyte‐adipocyte differentiation.

Results

The RNAseq‐based tissue distribution expression screen identified SLC19A3 (encoding the thiamine transporter 2) as adipose tissue‐specific. SLC19A3 expression was higher in subcutaneous compared with omental adipose tissue in both sample sets (p = 0.043 and p < 0.001). Preadipocyte differentiation towards adipocytes resulted in increased SLC19A3 gene expression (p = 0.018 or less at all‐time points). Subcutaneous adipose tissue expression of SLC19A3 was lower in persons with high BMI in both cohorts (p = 0.008, and p < 0.001) and increased during a weight‐loss intervention (p = 0.006).

Conclusion

The specific adipose tissue expression pattern of SLC19A3, together with its regulation in obesity and during weight loss, indicate that it plays a key role in adipocyte metabolism.
Either transepidermal water loss rates or stratum corneum hydration levels can predict quality of life in children with atopic dermatitis
Authors: Wang Shan , Shen Chunping , Zhao Mutong , Jiao Lei , Tian Jing , Wang Yang , Ma Lin , Man Mao‐Qiang
Published: June 2021

Importance

Patients with atopic dermatitis (AD) display compromised epidermal barrier and suffer from poor quality of life. We hypothesized that quality of life could reflect in the changes in the epidermal barrier function.

Objective

To determine whether the epidermal barrier function correlates with the severity of pruritus and/or life quality in children with AD.

Methods

A total of 120 children, aged 0–12 years, with moderate AD were enrolled. Children were topically treated with topical corticosteroids (TCS) and an emollient for 2 weeks. The Eczema Area and Severity Index (EASI), visual analogue scale (VAS) for pruritus severity, the Infant’s Dermatitis Quality of Life Index (IDQOL) and the Children’s Dermatology Life Quality Index (CDLQI) were evaluated. Transepidermal water loss (TEWL) rates, stratum corneum (SC) hydration, and skin surface pH were measured. Correlations of epidermal barrier function with pruritus, life quality, and EASI were determined.

Results

Following 2‐week treatments, significant improvements were observed in EASI, TEWL, SC hydration, the VAS of pruritus, as well as DQOL (P < 0.001 for all). TEWL positively, while SC hydration negatively correlated with VAS pruritus, DQOL, and EASI (P < 0.001).

Interpretation

Both TEWL and SC hydration levels can serve as indicators of the severity of pruritus and quality of life in children with AD.
Assessing the activation/inhibition of tyrosine kinase‐related pathways with a newly developed platform
Authors: Kagiwada Harumi , Kiboku Takayuki , Matsuo Hitomi , Kitazawa Masashi , Fukui Kazuhiko , Horimoto Katsuhisa
Published: June 2021

The phosphorylation of cellular proteins plays a crucial role in the transduction of various signals from outside the cell into the nucleus. The signals are transduced by phosphorylation chain reactions within multiple pathways; however, determining which pathways are responsible for each defined signal has proven challenging. To estimate the activity of each pathway, we developed a phosphorylation array platform comprising a protein array with 1200 proteins belonging to 376 signalling pathways and an analytical method to estimate pathway activity based on the phosphorylation levels of proteins. The performance of our system was assessed by reconstructing kinase–substrate relationships, as well as by estimating pathway activity upon epidermal growth factor (EGF) stimulation and the pharmacological inhibition of epidermal growth factor receptor (EGFR). As a result, kinase–substrate relationships were reliably reconstructed based on the precise measurement of phosphorylation levels of constituent proteins on the array. Furthermore, the pathway activities associated with EGF stimulation and EGFR inhibition were successfully traced through the related pathways from the outer membrane to the nucleus along a time course. Thus, our phosphorylation array system can effectively assess the activity of specific signalling pathways that are perturbed by extracellular stimuli, such as various drugs.
Fluorene‐based donor‐acceptor‐type multifunctional polymer with bicarbazole pendant moiety for optoelectronic applications
Authors: Pıravadılı Selin , Doyranlı Ceylan , Altınısık Sinem , Bilgili Hakan , Canımkurbey Betül , Koyuncu Sermet
Published: June 2021

Since limited examples are in the literature in which both organic light‐emitting diodes (OLEDs) and electrochromic (EC) applications were performed using the same conjugated polymer, we presented comprehensive EC and electroluminescence (EL) studies of fluorene‐based electroactive polymer (e.g., CFP6) consisting of a bicarbazole pendant moiety with quinoxaline as an acceptor bridge. CFP6 was synthesized by a Suzuki cross‐coupling polymerization reaction and utilized as an active and emissive layers of the electrochromic device (ECD) and OLED, respectively, due to its high photoluminescence quantum yield intensity and fine thin film forming capability. The optical, electrochemical, cyclic voltammetry measurements, and density functional theory calculations were realized. Electrochemical cross‐linking process was applied over the electroactive carbazole subunit of the CFP6 polymer. After the crosslinking process, EC performance was greatly improved. On the other hand, light emission and EL characteristics of OLEDs based on CFP6 emissive layer were realized in detail with six different device architectures to understand light output profile behavior. As a result, CFP6 emitted bright greenish yellow emission with a maximum brightness of 1777 cd/m2 at 215 mA/cm2 in the indium tin oxide (ITO)/poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)/CFP6:%10 4,4′‐bis(N‐carbazolyl)‐1,1′‐biphenyl (CBP)/Alq3/LiF/Al device architecture.
Solution structure of the anticancer p28 peptide in biomimetic medium
Authors: Cantini Francesca , Gianni' Paola , Savarin Philippe , Bizzarri Anna Rita , Sette Marco
Published: June 2021

The p28 peptide derived from Pseudomonas aeruginosa azurin shows an anticancer activity after binding to p53 protein and is currently in Phase I of clinical trials. We have studied its structure in water and in a biomimetic media and show that the peptide is unstructured in water but when studied in a biomimetic medium assumes a structure very similar to the one observed in azurin, suggesting a high propensity of this peptide to maintain this secondary structure. Analysis of p28 sequences from different bacterial species indicates conservation of the secondary structure despite amino acid replacement in different positions, suggesting that others, similar peptides could be tested for binding to p53.
Observer‐based consensus control for heterogeneous multi‐agent systems with intermittent communications
Authors: Zhang Yuhang , Jiang Yulian , Wang Shenquan , Ai Xiaolin
Published: June 2021

In this article, the output consensus tracking problem for a class of heterogeneous multiagent systems (HMASs) with intermittent communications is studied. We first design a local observer for each agent to estimate unmeasurable state information of followers', and an adaptive distributed estimator is constructed for each follower to estimate the leader's state. Then a type of switched and distributed tracking controllers for HMASs are established under the intermittent communications, and relative parameters of the novel controllers are designed via the constructed regulation equation. Furthermore, by using the switching system theory and LMI technology, both the sufficient conditions for HMASs to achieve output consensus tracking and the threshold of communication rate are obtained, and simultaneously the controller gain and observer gain matrices are constructed. Finally, a simulation example is provided for general HMASs to verify the correctness and effectiveness of the proposed method.
A (non‐central) chi‐squared mixture of non‐central chi‐squareds is (non‐central) chi‐squared and related results, corollaries and applications
Authors: Jones M. C. , Marchand Éric
Published: June 2021

Our main, novel, result is that a certain non‐central chi‐squared mixture of non‐central chi‐squared distributions is itself a scaled non‐central chi‐squared distribution. From this and a link to a known result on a mixture representation for a scaled central chi‐squared distribution, numerous further mixture results, both old and new, ensue. These include mixture results for centralF, non‐centralFand Libby–Novick distributions. The main result involves distributions all with the same degrees of freedom; it is also extended to the case where the mixing non‐central chi‐squared distribution has degrees of freedom an even number larger than that of the conditional non‐central chi‐squared distribution, with further consequences pursued.
An international, randomized, placebo‐controlled, phase 2b clinical trial of intepirdine for dementia with Lewy bodies (HEADWAY‐DLB)
Authors: Lang Frederick M. , Kwon Daniel Y. , Aarsland Dag , Boeve Brad , Tousi Babak , Harnett Mark , Mo Yi , Noel Sabbagh Marwan
Published: June 2021

Introduction

A phase 2b clinical trial, HEADWAY‐DLB, was performed to assess treatment with intepirdine, a serotonin receptor antagonist, in patients with dementia with Lewy bodies (DLB).

Methods

HEADWAY‐DLB was a multinational, double‐blind, randomized, placebo‐controlled study. Two hundred sixty‐nine DLB patients were randomized to receive placebo, 70 mg/day intepirdine, or 35 mg/day intepirdine over 24 weeks. The primary endpoint was change from baseline to week 24 on the Unified Parkinson's Disease Rating Scale–Part III (UPDRS‐III).

Results

Both intepirdine groups did not demonstrate significant benefits over placebo at 24 weeks on the UPDRS‐III (35 mg/day: P = .1580, 70 mg/day: P = .6069). All other endpoints were not significant. Intepirdine was well tolerated, with a slightly higher incidence of gastrointestinal adverse events observed in the intepirdine groups versus placebo.

Discussion

Intepirdine treatment did not lead to improvements over placebo in patients with DLB. As one of the largest DLB studies to date, HEADWAY‐DLB demonstrates that international trials for DLB are feasible within a reasonable timeframe.
Anaesthetic management of 10 horses undergoing cervical intervertebral body fusion ‘wobbler surgery’
Authors: Loomes Kate , Jopling Patrick
Published: June 2021

Surgical techniques for cervical intervertebral body fusion ‘wobbler surgery’ are frequently reported in the literature, but the anaesthetic management is rarely described. Considering the invasive and complex nature of the surgical procedure, prolonged anaesthetic duration and potential for pre‐existing and post‐operative neurological deficits, the anaesthetic and analgesic approach poses specific challenges. This article aims to discuss the anaesthetic management, intra‐operative complications and recovery experience in 10 horses undergoing surgical treatment of cervical spinal cord compression. The four types of intra‐operative complication encountered generally responded well to first‐line treatment. All horses recovered successfully, and recovery quality, in most cases, was good despite the presence of several factors known to adversely affect recovery quality. However, the need for additional intra‐operative ketamine and relatively high isoflurane concentrations to obtain an adequate anaesthetic depth despite provision of partial intravenous anaesthesia and multi‐modal analgesia indicates that further analgesic techniques may be warranted.
Prediction intervals for Poisson‐based regression models
Authors: Kim Taeho , Lieberman Benjamin , Luta George , Peña Edsel A.
Published: June 2021

This paper provides a review of the literature regarding methods for constructing prediction intervals for counting variables, with particular focus on those whose distributions are Poisson or derived from Poisson and with an over‐dispersion property. Independent and identically distributed models and regression models are both considered. The motivating problem for this review is that of predicting the number of daily and cumulative cases or deaths attributable to COVID‐19 at a future date.

This article is categorized under:

Applications of Computational Statistics > Clinical Trials

Statistical Learning and Exploratory Methods of the Data Sciences > Modeling Methods

Statistical Models > Generalized Linear Models
New data on the metabolism of chloromethylisothiazolinone and methylisothiazolinone in human volunteers after oral dosage: excretion kinetics of a urinary mercapturic acid metabolite (“M-12”)
Authors: Schettgen Thomas , Bertram J. , Kraus T.
Published: June 2021

Methylisothiazolinone (MI) as well as the mixture of chloromethylisothiazolinone/methylisothiazolinone [MCI/MI (3:1)] are biocides that are used in a variety of products of every-day life. Due to the skin sensitizing properties of these biocides, their use has come under scrutiny. We have previously examined the human metabolism of MI and MCI after oral dosage of isotope-labelled analogues in human volunteers and confirmed N-methylmalonamic acid to be a major, but presumably unspecific human urinary metabolite. In the present study, we have investigated the urinary kinetics of a mercapturic acid metabolite of MI and MCI using the same set of samples. Four human volunteers received 2 mg of isotopically labelled MI and MCI separately and at least 2 weeks apart. Consecutive urine samples were collected over 48 h and were examined for the content of the (labelled) 3-mercapturic acid conjugate of 3-thiomethyl-N-methyl-propionamide (“M-12”), a known metabolite in rats. On a molar basis, M-12 represented 7.1% (3.0–10.1%) of the dose excreted in urine after dosage of MI. Excretion of this mercapturate was fast with a mean half-life of 3.6 h. Surprisingly, for MCI the mercapturate M-12 represented only 0.13% of the dose excreted in urine. Thus, this biomarker is highly specific for exposures to MI and might be used to distinguish between different exposure patterns of these biocides [use of MI or MCI/MI (3:1)] in the general population.
Holocene vegetation, fire and land use dynamics at Lake Svityaz, an agriculturally marginal site in northwestern Ukraine
Authors: Schwörer Christoph , Gobet Erika , van Leeuwen Jacqueline F. N. , Bögli Sarah , Imboden Rachel , van der Knaap W. O. , Kotova Nadezhda , Makhortykh Sergej , Tinner Willy
Published: June 2021

Observing natural vegetation dynamics over the entire Holocene is difficult in Central Europe, due to pervasive and increasing human disturbance since the Neolithic. One strategy to minimize this limitation is to select a study site in an area that is marginal for agricultural activity. Here, we present a new sediment record from Lake Svityaz in northwestern Ukraine. We have reconstructed regional and local vegetation and fire dynamics since the Late Glacial using pollen, spores, macrofossils and charcoal. Boreal forest composed of Pinus sylvestris and Betula with continental Larix decidua and Pinus cembra established in the region around 13,450 cal bp, replacing an open, steppic landscape. The first temperate tree to expand was Ulmus at 11,800 cal bp, followed by Quercus, Fraxinus excelsior, Tilia and Corylus ca. 1,000 years later. Fire activity was highest during the Early Holocene, when summer solar insolation reached its maximum. Carpinus betulus and Fagus sylvatica established at ca. 6,000 cal bp, coinciding with the first indicators of agricultural activity in the region and a transient climatic shift to cooler and moister conditions. Human impact on the vegetation remained initially very low, only increasing during the Bronze Age, at ca. 3,400 cal bp. Large-scale forest openings and the establishment of the present-day cultural landscape occurred only during the past 500 years. The persistence of highly diverse mixed forest under absent or low anthropogenic disturbance until the Early Middle Ages corroborates the role of human impact in the impoverishment of temperate forests elsewhere in Central Europe. The preservation or reestablishment of such diverse forests may mitigate future climate change impacts, specifically by lowering fire risk under warmer and drier conditions.
Correction to: Einstein, von Frisch and the honeybee: a historical letter comes to light
Authors: Dyer Adrian G. , Greentree Andrew D. , Garcia Jair E. , Dyer Elinya L. , Howard Scarlett R. , Barth Friedrich G.
Published: June 2021

A correction to this paper has been published: https://doi.org/10.1007/s00359-021-01497-z.
Hypoglossal nerve stimulation for obstructive sleep apnea: updated position paper of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery
Authors: Steffen Armin , Heiser Clemens , Galetke Wolfgang , Herkenrath Simon-Dominik , Maurer Joachim T. , Günther Eck , Stuck Boris A. , Woehrle Holger , Löhler Jan , Randerath Winfried
Published: June 2021

Since the first statement of the German Society of Oto-Rhino-Laryngology, hypoglossal nerve stimulation (HNS) is meanwhile an established treatment option for obstructive sleep apnea (OSA). There are three HNS systems available in Germany which differ in their technical details of the underlying comparable basic principle. For the unilateral HNS with respiratory sensing, several comparative studies, high-volume register analysis and long-term reports exist. The continuous HNS without respiratory sensing does not require a sleep endoscopy for indication. For the bilateral continuous HNS as the single partially implantable device, a feasibility study exists. For indication, the assessment of positive airway pressure failure by sleep medicine is crucial, and the decision for HNS should be made in discussion of other treatment options for at least moderate OSA. The implantation center holds primarily responsibility among the interdisciplinary sleep team and is primary contact for the patient in problems. This depicts why structural processes are required to secure outcome quality and minimize the complications. The aftercare of HNS patients can be provided interdisciplinary and by different medical institutions, whereat, minimal reporting standards to document outcome and usage are recommended.
Nuclear expression of VDR and AHR is mutually exclusive in glandular cells in endometriosis
Authors: De Pascali Francesco , Casarini Livio , Kuhn Christina , Simoni Manuela , Mahner Sven , Jeschke Udo , von Schönfeldt Viktoria
Published: June 2021

The vitamin D receptor (VDR) and aryl hydrocarbon receptor (AHR) are two nuclear receptors that exert their effects by binding with ligands and forming a molecular complex. These complexes translocate to the nucleus and activate the expression of a series of genes which have a response element to VDR or AHR. Both receptors have been identified in the pathogenesis of endometriosis, a common disease characterized by the formation of endometrium-like tissue in ectopic zones. Despite numerous therapies, there is no definitive cure for endometriosis at the pharmacological level. Our study aims to describe the location and the expression of VDR and AHR at the protein level. For this purpose, an evaluation was performed using tissue from the three normal phases of the endometrium (proliferative, early, and late secretory) and in endometriosis by immunohistochemistry, using anti-VDR and anti-AHR antibodies. We demonstrate that in the nuclei of glandular cells in endometriosis, the expression of VDR and AHR is mutually exclusive—when the expression of one receptor is high, the other one is low—suggesting a possible target in the treatment of endometriosis. We also identify a significant change in the expression of glandular cytoplasmic AHR between the proliferative and late secretory endometrium.
Optimum insurance contract of flood damage index insurance for rice farmers in Myanmar
Authors: Furuya Jun , Mar Swe Swe , Hirano Akira , Sakurai Takeshi
Published: June 2021

Climate change is an underlying cause of many extreme events such as enormous cyclones and erratic torrential rains. These phenomena threaten farmers in coastal regions of Myanmar. Self-insurance through means such as crop diversification is insufficient for sustainable farm management. Weather index insurance (WII) is receiving much attention because of its low management costs. An optimum WII contract for flood damage using rainfall as the index has been proposed for rice farmers in coastal regions. According to the model, an insurance payment demand function is derived by solving the expected utility maximization problem. The utility function of the contract is specified as constant relative risk aversion type. The production function is specified as Cobb–Douglas type. By substituting real average data of rice production of farmers into this function, the optimum insurance payment and premium are obtained. Changes in insurance compensation by payments according to an increase in the price of rice, rainfall, and degree of risk aversion are investigated. Results suggest that if an average farmer pays around 41.5 US dollars per year, then farm management will be optimally stabilized under the flood risk.
Application of the subsecond calorimetry technique with both contact and radiance temperature measurements: case study on solid phase tungsten at very high temperatures
Authors: Milošević Nenad D.
Published: June 2021

This work presents an application of the subsecond calorimetry technique at very high temperatures, which uses both contact and radiance temperature measurements. This technique is normally applied for thermophysical characterization of high temperature solid phase materials in the temperature range from ambient up to about 2600 K, which is the limit of the standard tungsten-rhenium thermocouple use. Simultaneously with contact temperature measurements, noncontact or radiance temperature detection may be performed in the approximate range from 1000 to 2600 K in order to acquire information on spectral normal emissivity of specimen under test. In this study, however, the specimen is heated above 2600 K and, then, the temperature is measured only by the noncontact mean. In the extended temperature range, the obtained values of the spectral normal emissivity are extrapolated for each experimental run, which makes possible a conversion from radiance to absolute specimen temperature. In order to test this application, a pure polycrystalline specimen of tungsten in the form of rod, 3 mm in diameter and 200 mm in length, has been used. The specimen has been heated in vacuum environment of about 10–4 mbar by short pulses of high DC current with a gradual increase of the total heating time from about 0.5–2.5 s. During the specimen heating and the beginning of the cooling period, four sets of experimental data have been recorded and reduced by using the corresponding data reduction procedure. Obtained results of specific heat and specific electrical resistivity from ambient to 3700 K, total hemispherical emissivity from 1000 to 3700 K and spectral normal emissivity from 1000 to 2600 K (extrapolated to 3700 K) are presented, discussed and compared with related literature data.
Gel Strength of Hydrophilic Matrix Tablets in Terms of In Vitro Robustness
Authors: Goldoozian Seyedreza , Mohylyuk Valentyn , Dashevskiy Andriy , Bodmeier Roland
Published: June 2021

Purpose

The purpose of this study was to correlate the gel strength of swollen matrix tablets with theirin vitrorobustness against agitation intensity and applied mechanical forces. Five commercial products, i.e. Glucophage®, Alfuzosin®, Tromphyllin®, Preductal® MR and Quetiapin® formulated as water-soluble/erodible matrix tablets were investigated.

Methods

Effect of agitation speed (50–150 rpm) on drug release, hydration/erosion and gel strength was investigated using USP paddle apparatus II. The gel strength of matrix tablets during dissolution at different conditions was characterized by a texture analyzer.

Results

Commercial tablets formulated with HPMC of higher viscosity, such as K15M or K100M, demonstrated the gel strength in swollen state >0.02 MPa. In this case, the release mechanism was predominantly diffusional and, therefore, not affected by stirring speed and mechanical stress. In contrast, the Quetiapin® matrix tablet, formulated with HPMC K 4 M in amount of approx. 25%, demonstrated the gel strength dropped below 0.02 MPa after 6 h of release. In this case, the drug was predominantly released via erosional mechanism and very susceptible to stirring speed.

Conclusion

Sufficient gel strength of swollen tablets is an important prerequisite for unchangedin vitroperformance in consideration of mechanical stress.
Measuring local competitiveness: comparing and integrating two methods PCA and AHP
Authors: Kurek Katarzyna A. , Heijman Wim , van Ophem Johan , Gędek Stanisław , Strojny Jacek
Published: June 2021

This article discusses two methods to measure the concept of local competitiveness: Principal Component Analysis (PCA) and Analytical Hierarchy Process (AHP). The goal of this analysis is to determine whether these two methods used in social sciences research lead to comparable model results. By non-parametric tests we show that there is a significant correlation between the PCA and AHP local competitiveness indexes. Thereafter, a developed mixed method examination of whether the methods can be used interchangeably is presented and illustrated with detailed examples of two mixed approaches. The mixed method confirms the correlation between the PCA and AHP models. However, the mixed modelling results indicate the utility of the PCA in the situation of a multicriteria local competitiveness data examination.
Online Percentile Estimation (OPE)
Authors: Kilpi Jorma , Kyntäjä Timo , Räty Tomi
Published: June 2021

We describe a control loop over a sequential online algorithm. The control loop either computes or uses the sequential algorithm to estimate the temporal percentiles of any univariate input data sequence. It transforms an input sequence of numbers into output sequence of histograms. This is performed without storing or sorting all of the observations. The algorithm continuously tests whether the input data is stationary, and reacts to events that do not appear to be stationary. It also indicates how to interpret the histograms since their information content varies according to whether a histogram was computed or estimated. It works with parameter-defined, fixed-size small memory and limited CPU power. It can be used for a statistical reduction of a numerical data stream and, therefore, applied to various Internet of Things applications, edge analytics or fog computing. The algorithm has a built-in feasibility metric called applicability. The applicability metric indicates whether the use of the algorithm is justified for a data source: it works for an arbitrary univariate numerical input, but it is statistically feasible only under some requirements, which are explicitly stated here. We also show the results of a performance study, which was executed on the algorithm with synthetic data.
Automating Periodontal bone loss measurement via dental landmark localisation
Authors: Danks Raymond P. , Bano Sophia , Orishko Anastasiya , Tan Hong Jin , Moreno Sancho Federico , D’Aiuto Francesco , Stoyanov Danail
Published: June 2021

Purpose

Periodontitis is the sixth most prevalent disease worldwide and periodontal bone loss (PBL) detection is crucial for its early recognition and establishment of the correct diagnosis and prognosis. Current radiographic assessment by clinicians exhibits substantial interobserver variation. Computer-assisted radiographic assessment can calculate bone loss objectively and aid in early bone loss detection. Understanding the rate of disease progression can guide the choice of treatment and lead to early initiation of periodontal therapy.

Methodology

We propose an end-to-end system that includes a deep neural network with hourglass architecture to predict dental landmarks in single, double and triple rooted teeth using periapical radiographs. We then estimate the PBL and disease severity stage using the predicted landmarks. We also introduce a novel adaptation of MixUp data augmentation that improves the landmark localisation.

Results

We evaluate the proposed system using cross-validation on 340 radiographs from 63 patient cases containing 463, 115 and 56 single, double and triple rooted teeth. The landmark localisation achieved Percentage Correct Keypoints (PCK) of 88.9%, 73.9% and 74.4%, respectively, and a combined PCK of 83.3% across all root morphologies, outperforming the next best architecture by 1.7%. When compared to clinicians’ visual evaluations of full radiographs, the average PBL error was 10.69%, with a severity stage accuracy of 58%. This simulates current interobserver variation, implying that diverse data could improve accuracy.

Conclusions

The system showed a promising capability to localise landmarks and estimate periodontal bone loss on periapical radiographs. An agreement was found with other literature that non-CEJ (Cemento-Enamel Junction) landmarks are the hardest to localise. Honing the system’s clinical pipeline will allow for its use in intervention applications.
Linear Groups with Restricted Conjugacy Classes
Authors: Giovanni F. de , Trombetti M. , Wehrfritz B. A. F.
Published: June 2021

In this paper we characterize, in terms of their conjugacy classes, linear groups G such that $$G/\zeta _k(G)$$

G
/

ζ
k

(
G
)

belongs to a certain group class $$\mathfrak {X}$$
X
for several natural choices of $$\mathfrak {X}$$
X
. Moreover, a description is given of linear groups with restrictions on layers.
Healthcare personnel experiences implementing carbapenem-resistant Enterobacterales infection control measures at a ventilator-capable skilled nursing facility—A qualitative analysis
Authors: Rynkiewich Katharina R. , Makhija Jinal , Froilan Mary Carl M. , Benson Ellen C. , Han Alice , Trick William E. , Weinstein Robert A. , Hayden Mary K. , Lin Michael Y. ,   CDC Prevention Epicenters Program
Published: June 2021

Objective:

Ventilator-capable skilled nursing facilities (vSNFs) are critical to the epidemiology and control of antibiotic-resistant organisms. During an infection prevention intervention to control carbapenem-resistantEnterobacterales(CRE), we conducted a qualitative study to characterize vSNF healthcare personnel beliefs and experiences regarding infection control measures.

Design:

A qualitative study involving semistructured interviews.

Setting:

One vSNF in the Chicago, Illinois, metropolitan region.

Participants:

The study included 17 healthcare personnel representing management, nursing, and nursing assistants.

Methods:

We used face-to-face, semistructured interviews to measure healthcare personnel experiences with infection control measures at the midpoint of a 2-year quality improvement project.

Results:

Healthcare personnel characterized their facility as a home-like environment, yet they recognized that it is a setting where germs were ‘invisible’ and potentially ‘threatening.’ Healthcare personnel described elaborate self-protection measures to avoid acquisition or transfer of germs to their own household. Healthcare personnel were motivated to implement infection control measures to protect residents, but many identified structural barriers such as understaffing and time constraints, and some reported persistent preference for soap and water.

Conclusions:

Healthcare personnel in vSNFs, from management to frontline staff, understood germ theory and the significance of multidrug-resistant organism transmission. However, their ability to implement infection control measures was hampered by resource limitations and mixed beliefs regarding the effectiveness of infection control measures. Self-protection from acquiring multidrug-resistant organisms was a strong motivator for healthcare personnel both outside and inside the workplace, and it could explain variation in adherence to infection control measures such as a higher hand hygiene adherence after resident care than before resident care.
Associations of dietary PUFA with dyslipidaemia among the US adults: the findings from National Health and Nutrition Examination Survey (NHANES) 2009–2016
Authors: Zhou Jiawei , Cai Lixin , Ni Senmiao , Zhong Zihang , Yang Min , Yu Hao , Zhao Yang , Xun Pengcheng , Bai Jianling
Published: June 2021

Dyslipidaemia, a significant risk factor of CVD, is threatening human health worldwide. PUFA are crucial long-chain fatty acids for TAG synthesis and removal, potentially decreasing dyslipidaemia risk. We examined dyslipidaemia prevalence among 15 244 adults aged ≥ 20 years from National Health and Nutrition Examination Survey 2009–2016. Dyslipidaemia was defined as total cholesterol ≥ 240 mg/dl, or HDL-cholesterol < 40 mg/dl/50 mg/dl for males/females, respectively, or LDL-cholesterol ≥ 160 mg/dl, or TAG ≥ 200 mg/dl, or taking lipid-modifying medications. We measured the daily PUFA intake using a 24-h dietary recall. Demographics, social economics, and lifestyle factors were collected using questionnaires/interviews. Additionally, we measured Se and Hg levels in the whole blood. Logistic regression models were used to examine the association between PUFA and dyslipidaemia. The unweighted and weighted dyslipidaemia prevalences were 72·4% and 71·0 %, respectively. When grouped into tertiles, PUFA intake above 19·524 g/d was associated with an independent 19 % decrease in dyslipidaemia risk (OR = 0·81 (95 % CI 0·71, 0·94)) compared with the lowest tertile (PUFA intake ≤ 12·349 g/d). A threshold inverse association was further determined by the restricted cubic spline analysis. When PUFA intake was increased to its turning point, that is, 19 g/d, the lower nadir risk for dyslipidaemia was obtained (OR = 0·72 (95 % CI 0·56, 0·89)). When the exposure was the sum of α-linolenic acid and octadecatetraenoic acid, the inverse linear association remained. Dietary PUFA intake is a beneficial factor for dyslipidaemia among American adults, independent of many potential confounders, including Hg and Se.