bluuebunny/crossref_metadata_2025_split huggingface dataset:
Particulate and drug-induced toxicity assessed in novel quadruple cell human primary hepatic disease models of steatosis and pre-fibrotic NASH
Authors: Kermanizadeh Ali , Valli Jessica , Sanchez Katarzyna , Hutter Simon , Pawlowska Agnieszka , Whyte Graeme , Moritz Wolfgang , Stone Vicki 
Published: October 2021

AbstractIn an effort to replace, reduce and refine animal experimentation, there is an unmet need to advance current in vitro models that offer features with physiological relevance and enhanced predictivity of in vivo toxicological output. Hepatic toxicology is key following chemical, drug and nanomaterials (NMs) exposure, as the liver is vital in metabolic detoxification of chemicals as well as being a major site of xenobiotic accumulation (i.e., low solubility particulates). With the ever-increasing production of NMs, there is a necessity to evaluate the probability of consequential adverse effects, not only in health but also in clinically asymptomatic liver, as part of risk stratification strategies. In this study, two unique disease initiation and maintenance protocols were developed and utilised to mimic steatosis and pre-fibrotic NASH in scaffold-free 3D liver microtissues (MT) composed of primary human hepatocytes, hepatic stellate cells, Kupffer cells and sinusoidal endothelial cells. The characterized diseased MT were utilized for the toxicological assessment of a panel of xenobiotics. Highlights from the study included: 1. Clear experimental evidence for the pre-existing liver disease is important in the augmentation of xenobiotic-induced hepatotoxicity and 2. NMs are able to activate stellate cells. The data demonstrated that pre-existing disease is vital in the intensification of xenobiotic-induced liver damage. Therefore, it is imperative that all stages of the wide spectrum of liver disease are incorporated in risk assessment strategies. This is of significant consequence, as a substantial number of the general population suffer from sub-clinical liver injury without any apparent or diagnosed manifestations.
The role of Raman spectroscopy in biopharmaceuticals from development to manufacturing
Authors: Esmonde-White Karen A. , Cuellar Maryann , Lewis Ian R. 
Published: October 2021

AbstractBiopharmaceuticals have revolutionized the field of medicine in the types of active ingredient molecules and treatable indications. Adoption of Quality by Design and Process Analytical Technology (PAT) frameworks has helped the biopharmaceutical field to realize consistent product quality, process intensification, and real-time control. As part of the PAT strategy, Raman spectroscopy offers many benefits and is used successfully in bioprocessing from single-cell analysis to cGMP process control. Since first introduced in 2011 for industrial bioprocessing applications, Raman has become a first-choice PAT for monitoring and controlling upstream bioprocesses because it facilitates advanced process control and enables consistent process quality. This paper will discuss new frontiers in extending these successes in upstream from scale-down to commercial manufacturing. New reports concerning the use of Raman spectroscopy in the basic science of single cells and downstream process monitoring illustrate industrial recognition of Raman’s value throughout a biopharmaceutical product’s lifecycle. Finally, we draw upon a nearly 90-year history in biological Raman spectroscopy to provide the basis for laboratory and in-line measurements of protein quality, including higher-order structure and composition modifications, to support formulation development.
Graphical abstract
LDA measurements in a one-sided ribbed square channel at Reynolds numbers of 50,000 and 100,000
Authors: Ruck Sebastian , Arbeiter Frederik 
Published: October 2021

Abstract
Laser Doppler anemometry (LDA) measurements in the fully developed turbulent flow through a one-sided rib-roughened square channel with a rib-height-to-channel-height ratio of $$k/H = 0.0667$$

k
/
H
=
0.0667

and a rib-pitch-to-rib-height ratio of $$p/k = 9$$

p
/
k
=
9

were carried out at Reynolds numbers (based on the channel height H and the mean bulk velocity $$u_B$$

u
B

) of $${Re}_H = 5.0 \cdot 10^4$$

Re

H

=
5.0
·

10
4

and $$1.0 \cdot 10^5$$

1.0
·

10
5

. Mean velocities, Reynolds normal, and shear stresses were determined. The first- and second-order statistical moments of the velocity differed slightly between both Reynolds numbers when normalized by the bulk velocity and the channel height. Deviations were attributed to a minor elongation increase in the large recirculation region behind the rib with increasing Reynolds numbers. The crucial role of turbulent diffusion was reflected in the non-coincidence of the maximum primary mean shear and the Reynolds normal stress as well as outward drifts of the Reynolds stress peaks along the rib crest. Turbulent diffusion contributed significantly to the turbulence kinetic energy (TKE) budget near the rib crest and within the separated shear layer, while mean convection made a remarkable contribution only at the rib leading edge. The detailed first- and second-order moments provide a basis for the validation of computational methods and turbulence models.

Graphic abstract
Health problems associated with single, multiple, and the frequency of months of objectively measured long working hours: a cohort study by the National Institute of Occupational Safety and Health, Japan
Authors: Ochiai Yuko , Takahashi Masaya , Matsuo Tomoaki , Sasaki Takeshi , Sato Yuki , Fukasawa Kenji , Araki Tsuyoshi , Otsuka Yasumasa 
Published: October 2021

Abstract
Purpose
We aimed to examine the prospective associations of monthly working hours measured in a month, the 6-month averaged hours, and the frequency of long working hours (≥ 205 h/month) during the past 6 months with health indicators.

Methods
This study included 6,806 Japanese company workers (response rate = 86.6%). Data on the workers’ monthly attendance during the second half of fiscal year 2016 and annual health checkups in fiscal years 2016 and 2017 were collected. We evaluated the association of the above three types of monthly working hours with subsequent health checkup data in fiscal year 2017. We adjusted for the corresponding data in fiscal year 2016.

Results
Multivariate logistic regression analyses revealed significant associations between monthly working hours and workers’ systolic and diastolic blood pressure as well as aspartate aminotransferase, alanine aminotransferase, low-density lipoprotein cholesterol (LDL), and triglyceride levels. However, the associations were not consistent between months. The average monthly working hours were significantly associated with higher LDL levels for the 220–240 h/mo group (OR: 1.49, 95%CI: 1.07–2.08) and lower triglyceride levels for the < 140 h/mo group (OR: 0.15, 95%CI: 0.03–0.77), compared to the 140–180 h/mo group. The frequency of long working hours was significantly associated with higher LDL levels.

Conclusions
Working hours over several months produced various associations with health indicators compared to those measured in a single month. Our present data suggest that the effects of average or frequency of long working hours during the past 6 months are likely to appear in LDL levels.
Upper and lower respiratory airway complaints among female veterinary staff
Authors: Hoffmeyer F. , Beine A. , Lotz A. , Kleinmüller O. , Nöllenheidt C. , Zahradnik E. , Nienhaus A. , Raulf M. 
Published: October 2021

Abstract
Objective
Working with animals is characterized by exposure to particulate, biological or chemical matter, and respiratory complaints are common. The aim of our cross-sectional study was to assess the prevalence of respiratory symptoms and diagnoses among veterinary staff.

Methods
Participants working in veterinary practices were examined and a detailed questionnaire was used to collect data. IgE tests to common and animal allergens were performed to specify sensitization. Associations with respiratory outcomes were analysed using logistic regression models while controlling for potential confounders.

Results
Atopy was seen in 31% of the 109 female participants. Symptoms of rhinoconjunctivitis were the most frequent complaints (n = 92; 84%). In 18% the diagnosis was confirmed by physicians. Symptoms of upper and lower airways were highly correlated and an asthma diagnosis was confirmed in 11% of participants. Modelling revealed that sensitization against cats/dogs was a significant risk factor for respiratory symptoms of upper [odds ratio (OR) 4.61; 95% confidence interval (CI) 1.13–18.81] and lower airways (OR 5.14; 95% CI 1.25–21.13), physician-confirmed rhinoconjunctivitis (OR 13.43; 95% CI 1.69–106.5) and asthma (OR 9.02; 95% CI 1.16–70.39) in assistant staff of small-animal practices.

Conclusions
In several cases, rhinoconjunctivitis worsened after entering the profession. Atopy and specific sensitization to cats/dogs were risk factors for health impairments. Thus, to implement preventive measures, veterinary practice staff should be educated that upper respiratory tract symptoms are not harmless and should be diagnosed and treated early.
Ultrastructure and functional morphology of the dorsal organs in Scoloplos armiger (Annelida, Sedentaria, Orbiniida)
Authors: Buhre Jana Sophia , Purschke Günter 
Published: October 2021

AbstractAnnelids and particularly polychaetes possess a great variety of sensory organs and respond to numerous sensory stimuli. Although eyes and nuchal organs are comparatively well studied, the so-called dorsal organs are among the lesser-known sense organs in aquatic annelids. Moreover, they are known to be restricted to only two out of approximately 80 families of polychaetes—Orbiniidae and Spionidae—which are not closely related. These organs have been regarded as segmentally repeated nuchal organs in the latter taxon, but in Orbiniidae, data are lacking, although it is known that the organs occur almost along the entire trunk except for the anterior-most segments. Furthermore, although the nuchal organ ultrastructure is known to be comparatively uniform for many polychaete species, a comparative investigation has not been conducted in Orbiniidae. To bridge this data gap, we examined an intertidal population of the widely distributed species Scoloplos armiger. Although not completely identical, nuchal and dorsal organs show a high degree of correspondence in the examined specimens. Moreover, both organs correspond to the general structure of nuchal organs. They comprise ciliated supportive cells and bipolar receptor cells and are innervated directly from the brain. The supportive cells form subcuticular spaces and olfactory chambers apically protected by specialized microvilli that house the sensory processes—cilia and microvilli—of the monociliated receptor cells. Therefore, it can be concluded that nuchal and dorsal organs are also identical in Orbiniidae. However, despite general correspondence with spionids, convergent evolution in the two taxa appears to be the most parsimonious interpretation.
Disparities in telehealth use: How should the supportive care community respond?
Authors: Dixit Niharika , Van Sebille Ysabella , Crawford Gregory B. , Ginex Pamela K. , Ortega Paz Fernandez , Chan Raymond J. 
Published: October 2021

Abstract
Telehealth use has increased in the setting of the COVID-19 pandemic. However, there are disparities in telehealth use based on age, income, race/ethnicity, low health, digital literacy, and limited English proficiency. There are multilevel barriers to telehealth use at the patient, health systems, telehealth portal, and policy levels. To ensure equity in telehealth services and to leverage these services to maximize the reach of health care services, concerted efforts are needed to design telehealth tools and workflows. It should include reimbursement for staff training, patient education, and technical support needed for telehealth use. Furthermore, ongoing monitoring and responsive modifications in the use of telehealth services are needed to promote telehealth equity.
Blink reflex in newly diagnosed and treated patients with Wilson’s disease
Authors: Bembenek Jan P. , Kiryluk Karolina , Inglot Ewa , Litwin Tomasz , Smoliński Łukasz , Członkowska Anna 
Published: October 2021

AbstractAbnormal blink reflex (BR) results mainly from the dysfunction of reticular brainstem pathways and is one of the features of degenerative brain disorders. We aimed to investigate whether patients with Wilson’s disease (WD) have abnormal BR. This was a prospective, observational, single-center study. BR was assessed in accordance with generally accepted standards in 44 newly diagnosed treatment-naïve and 66 treated patients with WD. Any abnormal parameters in BR were observed in 45.5% treatment-naïve patients and 37.9% treated patients (p = 0.429). We also did not observe significant differences in BR parameters and frequency of abnormal findings between treated and treatment naïve patients. Abnormal findings in any of the BR parameters were more frequent in patients with neurological vs. non-neurological presentation (57.5 vs. 28.6%, p = 0.002), present vs. absent Kayser–Fleischer ring (73 vs. 21.5%, p < 0.001), and typical vs. no typical WD abnormalities in brain MRI (50% vs. 24.4%, p = 0.009). In addition, longer median R1 and R2 latencies, both ipsilateral and contralateral, were significantly more frequent in neurological than non-neurological WD patients, those with Kayser–Fleischer rings, and those with abnormal MRI findings typical of WD. Our results confirm frequent BR abnormalities in WD, which may be explained by the pathological influence of copper deposits in the circuit linking the basal ganglia, cerebellum and brainstem.
Understanding patient-reported knowledge of hernia surgery: a quantitative study
Authors: Jiménez D. Rosselló , López-Cano M. , Gonçalves V. Rodrigues , Tremolosa M. Verdaguer , Serra J. Saludes , Bravo-Salva A. , Rodríguez J. A. Pereira 
Published: October 2021

Abstract
Purpose
The objective of this study was to gather information on patient-reported knowledge (PRK) in the field of hernia surgery.

Methods
A prospective quantitative study was designed to explore different aspects of PRK and opinions regarding hernia surgery. Patients referred for the first time to a surgical service with a presumed diagnosis of hernia and eventual hernia repair were eligible, and those who gave consent completed a simple self-assessment questionnaire before the clinical visit.

Results
The study population included 449 patients (72.8% men, mean age 61.5). Twenty (4.5%) patients did not have hernia on physical examination. The patient’s perceived health status was “neither bad nor good” or “good” in 56.6% of cases. Also, more patients considered that hernia repair would be an easy procedure (35.1%) rather than a difficult one (9.8%). Although patients were referred by their family physicians, 32 (7.1%) answered negatively to the question of coming to the visit to assess the presence of a hernia. The most important reason of the medical visit was to receive medical advice (77.7%), to be operated on as soon as possible (40.1%) or to be included in the surgical waiting list (35.9%). Also, 46.1% of the patients considered that they should undergo a hernia repair and 56.8% that surgery will be a definitive solution.

Conclusion
PRK of patients referred for the first time to an abdominal wall surgery unit with a presumed diagnosis of hernia was quite limited and there is still a long way towards improving knowledge of hernia surgery.
Open data products-A framework for creating valuable analysis ready data
Authors: Arribas-Bel Dani , Green Mark , Rowe Francisco , Singleton Alex 
Published: October 2021

AbstractThis paper develops the notion of “open data product”. We define an open data product as the open result of the processes through which a variety of data (open and not) are turned into accessible information through a service, infrastructure, analytics or a combination of all of them, where each step of development is designed to promote open principles. Open data products are born out of a (data) need and add value beyond simply publishing existing datasets. We argue that the process of adding value should adhere to the principles of open (geographic) data science, ensuring openness, transparency and reproducibility. We also contend that outreach, in the form of active communication and dissemination through dashboards, software and publication are key to engage end-users and ensure societal impact. Open data products have major benefits. First, they enable insights from highly sensitive, controlled and/or secure data which may not be accessible otherwise. Second, they can expand the use of commercial and administrative data for the public good leveraging on their high temporal frequency and geographic granularity. We also contend that there is a compelling need for open data products as we experience the current data revolution. New, emerging data sources are unprecedented in temporal frequency and geographical resolution, but they are large, unstructured, fragmented and often hard to access due to privacy and confidentiality concerns. By transforming raw (open or “closed”) data into ready to use open data products, new dimensions of human geographical processes can be captured and analysed, as we illustrate with existing examples. We conclude by arguing that several parallels exist between the role that open source software played in enabling research on spatial analysis in the 90 s and early 2000s, and the opportunities that open data products offer to unlock the potential of new forms of (geo-)data.
Juvenile idiopathic arthritis-associated uveitis in the era of biological therapy: how the disease changed in more than 20 years of observation in a tertiary referral center in Rome (Italy)
Authors: Del Giudice E. , Simio C. , Scala A. , Di Coste A. , La Torre G. , Spadea L. , Lubrano R. , Duse M. , Paroli M. P. 
Published: October 2021

Abstract
Objectives
To describe the ophthalmological characteristics in a Juvenile idiopathic arthritis (JIA) cohort and to evaluate how therapeutic advances have changed the course of the uveitis.

Methods
Analysis of a retrospective cohort study of consecutive JIA pediatric patients including JIA-associated uveitis (JIA-U) and comparison with a previous study in the same uveitis center assessed before the wide-spread of biological therapy.

Results
The total of 49 JIA patients were analyzed, of whom 18 JIA-U, compared with a JIA-U past cohort of 66 patients. Systemic corticosteroids were used significantly less in the current JIA-U group (p = 0.008) than in the past one. JIA-U present cohort was on therapy more frequently with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) than the past group (p = 0.039), mostly treated with methotrexate (93.3%). Furthermore, a larger use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) was described in the current JIA-U group (p = 0.005) also associated with csDMARDs (p = 0.003). Adalimumab was used more (72.7%) in the present JIA-U cohort compared to a larger treatment with infliximab (61.5%) in the past (p = 0.005). Higher number of uveitis recurrences was observed in the previous cohort compared to the current one (p = 0.005). Fewer complications were described in this study than in the previous: posterior synechiae (p = 0.007), cataract (p < 0.001), band keratopathy (p < 0.001), and elevated intraocular pressure (IOP) (p = 0.047).

Conclusion
Current therapies reduced the uveitis recurrences and ocular complications including cataract due also to the lower use of corticosteroids. The new close collaboration with the pediatric rheumatologic center in the same University has contributed to the care improvement and decrease of uveitis complications.
Pharmacokinetic/Pharmacodynamic Modeling of a Cell-Penetrating Peptide Phosphorodiamidate Morpholino Oligomer in mdx Mice
Authors: Mukashyaka Marie Claire , Wu Chia-Ling , Ha Kristin , Zhang Jianbo , Wood Jenna , Foley Samantha , Mastis Bryan , Jungels Nino , Sun Huadong , Shadid Mohammad , Harriman Shawn , Hadcock John R. 
Published: October 2021

Abstract
Purpose
Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) have shown promise in treating Duchenne muscular dystrophy (DMD). We evaluated a semi-mechanistic pharmacokinetic (PK) and pharmacodynamic (PD) model to capture the relationship between plasma and muscle tissue exposure/response in mdx mice treated by mouse surrogate PPMO.

Methods
A single or repeated (every 4 weeks for 20 weeks) intravenous PPMO dose was administered to mdx mice (n = 6/timepoint). A PK/PD model was built to characterize data via sequential modeling. A 2-compartment model was used to describe plasma PK. A simultaneous tissue PK/PD model was subsequently developed: 2-compartment model to describe muscle PK; linked to an indirect response model describing stimulation of synthesis of skipped transcript, which was in turn linked to stimulation of synthesis of dystrophin protein expression.

Results
Model performance assessment via goodness-of-fit plots, visual predictive checks, and accurate parameter estimation indicated robust fits of plasma PK and muscle PK/PD data. The model estimated a PPMO tissue half-life of 5 days—a useful parameter in determining the longevity of PPMOs in tissue and their limited accumulation after multiple doses. Additionally, the model successfully described dystrophin expression after single dosing and associated protein accumulation after multiple dosing (increasing ~ twofold accumulation from the first to last dose).

Conclusions
This first PK/PD model of a PPMO in a DMD disease model will help characterize and predict the time course of PK/PD biomarkers in mdx mice. Furthermore, the model framework can be used to develop clinical PK/PD models and can be extended to other exon-skipping therapies and species.
‘At first I was overwhelmed, but then—I have to say—I did almost enjoy it’. Psychological needs satisfaction and vitality of student teachers during the first Covid-19 lockdown
Authors: Carmignola Matteo , Martinek Daniela , Hagenauer Gerda 
Published: October 2021

AbstractAccording to Self-Determination Theory, the satisfaction of the three basic psychological needs (BPN) is crucial for optimal personal and academic development, as well as well-being, which is associated with the perceived vitality. These dimensions can be fostered or hindered by contextual factors within the work, study and personal environment. During the first COVID-19 lockdown, most social contexts for student teachers were substantially altered, for which we hypothesised negative outcomes with regards to perceived basic needs satisfaction and vitality. To investigate changes in needs satisfaction and subjective vitality during distance learning, this research applied an explanatory sequential mixed-methods design combining a quantitative and qualitative study. For the quantitative study, two surveys were conducted; the first before the lockdown (N = 161) and the second after the lockdown (N = 146). The purpose of these surveys was to test the interrelations between need satisfaction, frustration and vitality before and during the distance learning by implementing a SEM-based mediation analysis. In addition, we elaborated on significant and unexpected findings of the quantitative study by interviewing 14 other student teachers, allowing for an in-depth and contextualised understanding of the psychological changes in and the triggering factors of the ‘corona-lockdown’. Results stress the relevance of physical activity and time spent outdoors for the perception of vitality which was supported by a more flexible time structure during distance learning. For the context of distance learning, this research emphasises the relevance of BPN also in the context of online-based learning where higher levels of interaction with fellow students and lecturers, a clear course structure and formative feedback proved to be essential for motivational and achievement-related outcomes.