bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined renal and common hepatic artery denervation as a novel approach to reduce cardiometabolic risk: technical approach, feasibility and safety in a pre-clinical model
Authors: Kiuchi Márcio Galindo , Ganesan Kavitha , Keating John , Carnagarin Revathy , Matthews Vance B. , Herat Lakshini Y. , Goh Gerard , Adams Leon , Schlaich Markus P. 
Published: February 2021

Abstract
Background
Cardiovascular and metabolic regulation is governed by neurohumoral signalling in relevant organs such as kidney, liver, pancreas, duodenum, adipose tissue, and skeletal muscle. Combined targeting of relevant neural outflows may provide a unique therapeutic opportunity for cardiometabolic disease.

Objectives
We aimed to investigate the feasibility, safety, and performance of a novel device-based approach for multi-organ denervation in a swine model over 30 and 90 days of follow-up.

Methods
Five Yorkshire cross pigs underwent combined percutaneous denervation in the renal arteries and the common hepatic artery (CHA) with the iRF Denervation System. Control animals (n = 3) were also studied. Specific energy doses were administered in the renal arteries and CHA. Blood was collected at 30 and 90 days. All animals had a pre-terminal procedure angiography. Tissue samples were collected for norepinephrine (NEPI) bioanalysis. Histopathological evaluation of collateral structures and tissues near the treatment sites was performed to assess treatment safety.

Results
All animals entered and exited the study in good health. No stenosis or vessel abnormalities were present. No significant changes in serum chemistry occurred. NEPI concentrations were significantly reduced in the liver (− 88%, p = 0.005), kidneys (− 78%, p < 0.001), pancreas (− 78%, p = 0.018) and duodenum (− 95%, p = 0.028) following multi-organ denervation treatment compared to control animals. Histologic findings were consistent with favourable tissue responses at 90 days follow-up.

Conclusions
Significant and sustained denervation of the treated organs was achieved at 90 days without major safety events. Our findings demonstrate the feasibility of multi-organ denervation using a novel iRF Denervation System in a single procedure.
Functional analysis of a gene-edited mouse model to gain insights into the disease mechanisms of a titin missense variant
Authors: Jiang He , Hooper Charlotte , Kelly Matthew , Steeples Violetta , Simon Jillian N. , Beglov Julia , Azad Amar J. , Leinhos Lisa , Bennett Pauline , Ehler Elisabeth , Kalisch-Smith Jacinta I. , Sparrow Duncan B. , Fischer Roman , Heilig Raphael , Isackson Henrik , Ehsan Mehroz , Patone Giannino , Huebner Norbert , Davies Benjamin , Watkins Hugh , Gehmlich Katja 
Published: February 2021

AbstractTitin truncating variants are a well-established cause of cardiomyopathy; however, the role of titin missense variants is less well understood. Here we describe the generation of a mouse model to investigate the underlying disease mechanism of a previously reported titin A178D missense variant identified in a family with non-compaction and dilated cardiomyopathy. Heterozygous and homozygous mice carrying the titin A178D missense variant were characterised in vivo by echocardiography. Heterozygous mice had no detectable phenotype at any time point investigated (up to 1 year). By contrast, homozygous mice developed dilated cardiomyopathy from 3 months. Chronic adrenergic stimulation aggravated the phenotype. Targeted transcript profiling revealed induction of the foetal gene programme and hypertrophic signalling pathways in homozygous mice, and these were confirmed at the protein level. Unsupervised proteomics identified downregulation of telethonin and four-and-a-half LIM domain 2, as well as the upregulation of heat shock proteins and myeloid leukaemia factor 1. Loss of telethonin from the cardiac Z-disc was accompanied by proteasomal degradation; however, unfolded telethonin accumulated in the cytoplasm, leading to a proteo-toxic response in the mice.We show that the titin A178D missense variant is pathogenic in homozygous mice, resulting in cardiomyopathy. We also provide evidence of the disease mechanism: because the titin A178D variant abolishes binding of telethonin, this leads to its abnormal cytoplasmic accumulation. Subsequent degradation of telethonin by the proteasome results in proteasomal overload, and activation of a proteo-toxic response. The latter appears to be a driving factor for the cardiomyopathy observed in the mouse model.
Impact of increasing levels of adaptive statistical iterative reconstruction on image quality in oil-based postmortem CT angiography in coronary arteries
Authors: Steuwe Andrea , Boeven Judith , Cordes Lena , Draisci Stefano , Boos Johannes , Grabherr Silke , Bruguier Christine , Dalyanoglu Hannan , Antoch Gerald , Aissa Joel 
Published: February 2021

Abstract
Introduction
Postmortem multi-detector computed tomography (PMCT) has become an important part in forensic imaging. Modern reconstruction techniques such as iterative reconstruction (IR) are frequently used in postmortem CT angiography (PMCTA). The image quality of PMCTA depends on the strength of IR. For this purpose, we aimed to investigate the impact of different advanced IR levels on the objective and subjective PMCTA image quality.

Material and methods
We retrospectively analyzed the coronary arteries of 27 human cadavers undergoing whole-body postmortem CT angiography between July 2017 and March 2018 in a single center. Iterative reconstructions of the coronary arteries were processed in five different level settings (0%; 30%; 50%; 70%; 100%) by using an adaptive statistical IR method. We evaluated the objective (contrast-to-noise ratio (CNR)) and subjective image quality in several anatomical locations.

Results
Our results demonstrate that the increasing levels of an IR technique have relevant impact on the image quality in PMCTA scans in forensic postmortem examinations. Higher levels of IR have led to a significant reduction of image noise and therefore to a significant improvement of objective image quality (+ 70%). However, subjective image quality is inferior at higher levels of IR due to plasticized image appearance.

Conclusion
Objective image quality in PMCTA progressively improves with increasing level of IR with the best CNR at the highest IR level. However, subjective image quality is best at low to medium levels of IR. To obtain a “classic” image appearance with optimal image quality, PMCTAs should be reconstructed at medium levels of IR.
The impact of interrupting enzyme replacement therapy in late-onset Pompe disease
Authors: Wenninger Stephan , Gutschmidt Kristina , Wirner Corinna , Einvag Krisztina , Montagnese Federica , Schoser Benedikt 
Published: February 2021

Abstract
Background
Late-onset Pompe disease (LOPD) is a rare autosomal recessive disorder caused by mutations in the GAA gene, leading to progressive weakness of locomotor and respiratory muscles. Enzyme replacement therapy (ERT), administered every second week, has been proven to slow down disease progression and stabilize pulmonary function. Due to the COVID-19 pandemic in Germany, ERT was interrupted at our centre for 29 days. As reports on ERT discontinuation in LOPD are rare, our study aimed to analyse the impact of ERT interruption on the change in clinical outcome.

Methods
We performed a prospective cohort study in 12 LOPD patients. Clinical assessments were performed after ERT interruption and after the next three consecutive infusions. We assessed motor function by muscle strength testing, a 6-minute-walk-test, pulmonary function tests, and adverse events. For statistical analysis, an estimated baseline was calculated based on the individual yearly decline.

Results
The mean time of ERT interruption was 49.42 days (SD ± 12.54). During ERT interruption, seven patients reported 14 adverse events and two of them were severe. Frequent symptoms were reduced muscle endurance/increased muscle fatigability and shortness of breath/worsening of breathing impairment. After ERT interruption, significant deterioration was found for MIP%pred (p = 0.026) and MRC%pred, as well as a trend to clinical deterioration in FVC%pred and the 6MWT%pred.

Conclusion
Interruption of ERT was associated with a deterioration in the core clinical outcome measures. Therefore, an interruption of ERT should be kept as short as possible.
Relating Hydraulic–Electrical–Elastic Properties of Natural Rock Fractures at Elevated Stress and Associated Transient Changes of Fracture Flow
Authors: Sawayama K. , Ishibashi T. , Jiang F. , Tsuji T. , Fujimitsu Y. 
Published: February 2021

AbstractMonitoring the hydraulic properties within subsurface fractures is vitally important in the contexts of geoengineering developments and seismicity. Geophysical observations are promising tools for remote determination of subsurface hydraulic properties; however, quantitative interpretations are hampered by the paucity of relevant geophysical data for fractured rock masses. This study explores simultaneous changes in hydraulic and geophysical properties of natural rock fractures with increasing normal stress and correlates these property changes through coupling experiments and digital fracture simulations. Our lattice Boltzmann simulation reveals transitions in three-dimensional flow paths, and finite-element modeling enables us to investigate the corresponding evolution of geophysical properties. We show that electrical resistivity is linked with permeability and flow area regardless of fracture roughness, whereas elastic wave velocity is roughness-dependent. This discrepancy arises from the different sensitivities of these quantities to microstructure: velocity is sensitive to the spatial distribution of asperity contacts, whereas permeability and resistivity are insensitive to contact distribution, but instead are controlled by fluid connectivity. We also are able to categorize fracture flow patterns as aperture-dependent, aperture-independent, or disconnected flows, with transitions at specific stress levels. Elastic wave velocity offers potential for detecting the transition between aperture-dependent flow and aperture-independent flow, and resistivity is sensitive to the state of connection of the fracture flow. The hydraulic-electrical-elastic relationships reported here may be beneficial for improving geophysical interpretations and may find applications in studies of seismogenic zones and geothermal reservoirs.
A Cross University-Led COVID-19 Rapid-Response Effort: Design, Build, and Distribute Drexel AJFlex Face Shields
Authors: Throckmorton Amy L. , Bass Ellen J. , Ferrick Bryan , Ramakrishnan Arun , Eichmann Scott , Catucci Nicholas , Eshelman Bradley , McNamara John , Sundquist Erik , Beatson Nathan , Hirschhorn Matthew , Menon Pooja , Datner Elizabeth , Stevens Randy , Marcolongo Michele 
Published: February 2021

AbstractThe purpose of this article is to demonstrate how a new cross-community leadership team came together, collaborated, coordinated across academic units with external community partners, and executed a joint mission to address the unmet clinical need for medical face shields during these unprecedented times. Key aspects of this success include the ability to forge and leverage new opportunities, overcome challenges, adapt to changing constraints, and serve the significant need across the Philadelphia region and healthcare systems. We teamed to design-build durable face shields (AJFlex Shields). This was accomplished by high-volume manufacturing via injection molding and by 3-D printing the key headband component that supports the protective shield. Partnering with industry collaborators and civic-minded community allies proved to be essential to bolster production and deliver approximately 33,000 face shields to more than 100 organizations in the region. Our interdisciplinary team of engineers, clinicians, product designers, manufacturers, distributors, and dedicated volunteers is committed to continuing the design-build effort and providing Drexel AJFlex Shields to our communities.
Corporate social behaviour: Is it good for efficiency in the Chinese banking industry?
Authors: Fukuyama Hirofumi , Tan Yong 
Published: February 2021

AbstractWe develop an output-oriented data envelopment analysis framework to examine the efficiency of Chinese banks over the period 2007–2017 and further test the relationship between efficiency and corporate social responsibility (CSR). We are the first piece of research considering the number of employees as one bank input and potential increase in the number of employees as one CSR indicator. Additionally, we innovatively propose another three specific CSR indicators: namely donation, balance of green credits and loans to small and medium sized enterprises. The results show that the gain from improving allocative output-efficiency by reallocating variable inputs is less than the gain attained by improving technical output-efficiency. Evidence from the second-stage regression analysis shows that the overall indirect technical efficiency is significantly and negatively affected by the volumes of green credits, while an increase in the volumes of donations will improve the indirect allocative efficiency.
Challenges and Facilitators During Transitions from Adolescent Medium Secure Units to Adult Services in England: Interviews with Mental Healthcare Professionals
Authors: Livanou Maria , D’Souza Sophie , Lane Rebecca , La Plante Breanna , Singh Swaran P. 
Published: February 2021

AbstractYoung people moving from child and adolescent secure hospitals present with complex needs and vulnerabilities and are more likely to experience poor transition outcomes. Previous research has indicated the presence of several risk factors in periods of transition, such as poor liaison among services, lack of proper planning, shortage of beds in adult services, multiple transitions and lack of emotional readiness. However, little evidence exists about the processes and outcomes of transitions from adolescent secure services to adult settings. This study aims to bridge the gap in the existing literature by exploring the views and experiences of key professionals involved in the transition process from six adolescent medium secure units to nine adult secure and community services in England. Thirty-four key workers from 15 child and adolescent (N = 21) and adult (N = 13) forensic hospitals were interviewed to provide information about potential barriers and facilitators to transitions. Face-to-face semi-structured interviews were conducted between January 2016 and December 2017. Thematic analysis was used to identify challenges and facilitators to transitions. Three primary themes were identified: (1) transition processes and preparation; (2) transition barriers and challenges; (3) success factors to transition. Key differences in adult and adolescent service care-models and lack of emotional and developmental readiness to moving onto adult-oriented settings constitute major barriers to positive transition outcomes. Practice and policy implications are considered to address the need for service transformations.
Platelets as messengers of early-stage cancer
Authors: Sabrkhany Siamack , Kuijpers Marijke J. E. , oude Egbrink Mirjam G. A. , Griffioen Arjan W. 
Published: February 2021

AbstractPlatelets have an important role in tumor angiogenesis, growth, and metastasis. The reciprocal interaction between cancer and platelets results in changes of several platelet characteristics. It is becoming clear that analysis of these platelet features could offer a new strategy in the search for biomarkers of cancer. Here, we review the human studies in which platelet characteristics (e.g., count, volume, protein, and mRNA content) are investigated in early-stage cancer. The main focus of this paper is to evaluate which platelet features are suitable for the development of a blood test that could detect cancer in its early stages.
(+)-Usnic acid modulates the Nrf2-ARE pathway in FaDu hypopharyngeal carcinoma cells
Authors: Krajka-Kuźniak Violetta , Paluszczak Jarosław , Kleszcz Robert , Baer-Dubowska Wanda 
Published: February 2021

AbstractNaturally occurring phytochemicals of different origin and structure, arctigenin, bergenin, usnic acid and xanthohumol, were shown to affect Nrf2 pathway in the context of various diseases, but their effect on this pathway in cancer cells was not extensively investigated. This study aimed to evaluate the effect of these compounds on Nrf2 expression and activation in hypopharyngeal FaDu squamous cell carcinoma cells. FaDu cells were treated with 2 or 10 μM arctigenin, bergenin, (+)-usnic acid or xanthohumol for 24 h. While arctigenin, bergenin, and xanthohumol did not affect either Nrf2 expression or activation, (+)-usnic acid treatment increased its transcript level and increased the nuclear/cytosol Nrf2 protein ratio—the measure of Nrf2 pathway activation. Consequently, (+)-usnic acid enhanced the transcription and translation of Nrf2 target genes: NQO1, SOD, and to a lesser extent, GSTP. The treatment of FaDu cells with (+)-usnic acid decreased both GSK-3β transcript and protein level, indicating its possible involvement in Nrf2 activation. All the tested compounds decreased Bax mRNA but did not change the level of Bax protein. (+)-Usnic acid tended to increase the percentage of early apoptotic cells and LC3 protein, autophagy marker. Significant induction of p53 also was observed after treatment with (+)-usnic acid. In summary, the results of this study indicate that low concentrations of (+)-usnic acid activate Nrf2 transcription factor, most probably as a result of ROS accumulation, but do not lead to FaDu hypopharyngeal carcinoma cells death.
Can particulate matter be identified as the primary cause of the rapid spread of CoViD-19 in some areas of Northern Italy?
Authors: Collivignarelli Maria Cristina , Abbà Alessandro , Caccamo Francesca Maria , Bertanza Giorgio , Pedrazzani Roberta , Baldi Marco , Ricciardi Paola , Carnevale Miino Marco 
Published: February 2021

AbstractNorthern Italy was the most affected by CoViD-19 compared to other Italian areas and comprises zones where air pollutants concentration was higher than in the rest of Italy. The aim of the research is to determine if particulate matter (PM) has been the primary cause of the high CoViD-19 spread rapidity in some areas of Northern Italy. Data of PM for all the 41 studied cities were collected from the local environmental protection agencies. To compare air quality data with epidemiological data, a statistical analysis was conducted identifying the correlation matrices of Pearson and Spearman, considering also the possible incubation period of the disease. Moreover, a model for the evaluation of the epidemic risk, already proposed in literature, was used to evaluate a possible influence of PM on CoViD-19 spread rapidity. The results exclude that PM alone was the primary cause of the high CoVid-19 spread rapidity in some areas of Northern Italy. Further developments are necessary for a better comprehension of the influence of atmospheric pollution parameters on the rapidity of spread of the virus SARS-CoV-2, since a synergistic action with other factors (such as meteorological, socio-economic and cultural factors) could not be excluded by the present study.
Graphical abstract
Short-term effects of pesticide fipronil on behavioral and physiological endpoints of Daphnia magna
Authors: Bownik Adam , Szabelak Aleksandra 
Published: February 2021

AbstractFipronil (FIP) is an organic pesticide with many practical uses. Although some results indicated toxic effects in some terrestrial and aquatic animal species, little is known on its influence on behavioral and physiological endpoints of cladocerans. The aim of our study was to determine the short-term effects of FIP at concentrations of 0.1 μg/L, 1 μg/L, 10 μg/L, and 100 μg/L onDaphnia magnasublethal indices: behavioral (swimming speed, distance traveled) and physiological endpoints (heart rate, post-abdominal claw activity and thoracic limb movements). The results showed that FIP induced reduction of swimming speed and distance traveled in a concentration- and time-dependent manner at all the concentrations used. The lowest concentration of the insecticide temporarily stimulated post-abdominal claw activity after 24 h and thoracic limb activity after 48 h; however, the highest concentrations reduced all the studied physiological endpoints. IC50 values showed that thoracic limb activity, swimming speed, and distance traveled were most sensitive to FIP after 24-h exposure. The most sensitive parameter after 48 h and 72 h was swimming speed and post-abdominal claw activity, respectively. The study indicated that (i) behavioral and physiological endpoints ofDaphnia magnaare reliable and valuable sublethal indicators of toxic alterations induced by FIP; however, they respond with different sensitivity at various times of exposure, (ii) FIP may alter cladoceran behavior and physiological processes at concentrations detected in the aquatic environment; therefore, it should be considered as an ecotoxicological hazard to freshwater cladocerans.
Modularized iCBT‑I self-learn training for university staff—prevention and early intervention in the SARS-CoV-2 crisis
Authors: Schlarb Angelika A. , Fründ Jan Philipp , Kovacevic Tatjana , Faber Jasmin 
Published: February 2021

Abstract
Background
Insomnia is a widespread disease in adults and has a high prevalence rate. As sleep disturbances are a risk factor concerning mental and physical health, prevention and early intervention are necessary. Thus, the aim of this study was to implement a self-learning prevention and early intervention training for university staff members. We adapted an established cognitive behavioral therapy for insomnia (CBT-I) intervention as an online version for use during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) crisis.

Methods
Development and adaptation procedure of the internet-based CBT‑I (iCBT-I) prevention and early intervention training is described. Sessions and topics are shown in detail. The Online Sleep Prevention and Treatment Acceptance questionnaire (OSTA) and the Online Sleep Prevention and Treatment Feedback questionnaire (OSTF) were used to assess acceptance. Sleep problems of university staff members were assessed using the Pittsburgh Sleep Questionnaire (PSQI).

Results
The online-adapted version consisted of seven modules. Contents of sessions and topics were implemented based on video clips. Drawings were added to information regarding sleep and sleep hygiene as well as addressing stress and cognitions. In all, 15 individuals participated in this pilot study. The new iCBT‑I self-learning prevention training was well accepted. In addition, participants scored the online version as helpful based on the OSTA. Prior to online training, 89% of the participants reported impaired sleep quality or insomnia symptoms, and 56% had a PSQI score over 10. After training 78% of participants showed reduced sleep problems according to PSQI and 56% reached clinically significant enhancement. In addition, after training 44% were healthy sleepers.

Discussion
This is the first iCBT‑I prevention and early intervention training for university staff members. The training by participants was very well accepted and they scored the videos as very helpful. Sleep problems decreased after online training. However, further studies with larger samples and more sleep-related assessment strategies, e.g., actigraphy and sleep log, are necessary.