bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiotherapy-induced heart disease: a review of the literature
Authors: Zou Bingwen , Schuster Julius Philipp , Niu Kerun , Huang Qianyi , Rühle Alexander , Huber Peter Ernst 
Published: November 2019

Abstract
Radiotherapy as one of the four pillars of cancer therapy plays a critical role in the multimodal treatment of thoracic cancers. Due to significant improvements in overall cancer survival, radiotherapy-induced heart disease (RIHD) has become an increasingly recognized adverse reaction which contributes to major radiation-associated toxicities including non-malignant death. This is especially relevant for patients suffering from diseases with excellent prognosis such as breast cancer or Hodgkin’s lymphoma, since RIHD may occur decades after radiotherapy. Preclinical studies have enriched our knowledge of many potential mechanisms by which thoracic radiotherapy induces heart injury. Epidemiological findings in humans reveal that irradiation might increase the risk of cardiac disease at even lower doses than previously assumed. Recent preclinical studies have identified non-invasive methods for evaluation of RIHD. Furthermore, potential options preventing or at least attenuating RIHD have been developed. Ongoing research may enrich our limited knowledge about biological mechanisms of RIHD, identify non-invasive early detection biomarkers and investigate potential treatment options that might attenuate or prevent these unwanted side effects. Here, we present a comprehensive review about the published literature regarding clinical manifestation and pathological alterations in RIHD. Biological mechanisms and treatment options are outlined, and challenges in RIHD treatment are summarized.
Autoinflammatory disease with corneal and mucosal dyskeratosis caused by a novel NLRP1 variant
Authors: Herlin Troels , Jørgensen Sofie E , Høst Christian , Mitchell Patrick S , Christensen Maria Hønholt , Laustsen Mira , Larsen Dorthe A , Schmidt Florian I , Christiansen Mette , Mogensen Trine H 
Published: November 2019

Abstract

Objectives
Here we investigated a patient with inflammatory corneal intraepithelial dyskeratosis, mucosal inflammation, tooth abnormalities and, eczema to uncover the genetic and immunological basis of the disease.

Methods
On suspicion of an autoinflammatory condition, Sanger sequencing of nucleotide-binding oligomerization domain-like, leucine-rich repeat pyrin domain containing 1 (NLRP1) was performed and combined with an in vitro inflammasome reconstitution assay to measure caspase-1-mediated IL-1β cleavage, stimulation of patient peripheral blood mononuclear cells (PBMCs) and whole blood to measure IL-1β, IL-18 production and quantification of apoptosis-associated speck-like protein containing CARD (ASC) speck formation as a measure of inflammasome activation by flow cytometry.

Results
Sanger sequencing revealed a novel mutation (c.175G&gt;C, p.A59P; NM_33004.4) in the inflammasome molecule NLRP1 segregating with disease, although with incomplete penetrance, in three generations. We found that patient PBMCs produced increased IL-1β in response to inflammatory stimuli, as well as increased constitutive levels of IL-18. Moreover, we demonstrate that expression of the identified NLRP1 A59P variant caused spontaneous IL-1β cleavage to mature IL-1β. In addition, patient PBMCs responded to NLRP1 stimulation with increased ASC speck formation as a reflection of elevated inflammasome activity.

Conclusion
We demonstrate that this novel NLRP1 A59P variant caused increased activation of the NLRP1 inflammasome, resulting in constitutively and inducibly elevated IL-1β and IL-18 synthesis. We suggest the NLRP1 mutation underlies the pathogenesis of this rare autoinflammatory dyskeratotic disease inherited in an autosomal dominant manner with incomplete penetrance in the patient and within the family for several generations.
Metformin enhances the immunomodulatory potential of adipose-derived mesenchymal stem cells through STAT1 in an animal model of lupus
Authors: Jang Se Gwang , Lee Jaeseon , Hong Seung-Min , Kwok Seung-Ki , Cho Mi-La , Park Sung-Hwan 
Published: November 2019

AbstractObjectivesMesenchymal stem cells (MSCs) are considered potential therapeutic agents for treating autoimmune disease because of their immunomodulatory capacities and anti-inflammatory effects. However, several studies have shown that there is no consistency in the effectiveness of the MSCs to treat autoimmune disease, including SLE. In this study, we investigated whether metformin could enhance the immunoregulatory function of MSCs, what mechanism is relevant, and whether metformin-treated MSCs could be effective in an animal lupus model.MethodsAdipose-derived (Ad)-MSCs were cultured for 72 h in the presence of metformin. Immunoregulatory factors expression was analysed by real-time PCR and ELISA. MRL/lpr mice weekly injected intravenously with 1 × 106 Ad-MSCs or metformin-treated Ad-MSCs for 8 weeks. 16-week-old mice were sacrificed and proteinuria, anti-dsDNA IgG antibody, glomerulonephritis, immune complex, cellular subset were analysed in each group.ResultsMetformin enhanced the immunomodulatory functions of Ad-MSCs including IDO, IL-10 and TGF-β. Metformin upregulated the expression of p-AMPK, p-STAT1 and inhibited the expression of p-STAT3, p-mTOR in Ad-MSCs. STAT1 inhibition by siRNA strongly diminished IDO, IL-10, TGF-β in metformin-treated Ad-MSCs. As a result, metformin promoted the immunoregulatory effect of Ad-MSCs by enhancing STAT1 expression, which was dependent on the AMPK/mTOR pathway. Administration of metformin-treated Ad-MSCs resulted in significant disease activity improvement including inflammatory phenotype, glomerulonephritis, proteinuria and anti-dsDNA IgG antibody production in MRL/lpr mice. Moreover, metformin-treated Ad-MSCs inhibited CD4-CD8- T-cell expansion and Th17/Treg cell ratio.ConclusionMetformin optimized the immunoregulatory properties of Ad-MSCs and may be a novel therapeutic agent for the treatment of lupus.
Institution-driven innovation in Guangdong firms: Moderating effects of in-house formal R&D and industrial environment turbulence
Authors: Tang Yongli , Hu Xinyue , Petti Claudio , Thürer Matthias 
Published: November 2019

AbstractThis article explores the moderating effects of in-house formal R&D and industrial environment turbulence on the relationship between institutional drivers, in terms of incentives and pressures, and firm innovation. Hypotheses were tested on a sample of manufacturing firms in Guangdong Province of China, where institutional changes and governmental policies play prominent roles in shaping innovation. Results show a positive main effect of institutional incentives, but an insignificant main effect of institutional pressures. In-house formal R&D and industrial turbulence negatively moderate the institutional incentives–innovations relationship, yet positively moderate the institutional pressures–innovations relationship. This study links the innovation systems literature with the institution-based view and deepens the understanding of the joint forces of institutional transitions, industrial changes, and resource heterogeneity in shaping innovation. The findings also inform managers and policymakers in institutional transition environments to better manage institutional drivers of innovation by considering firm- and industry-specific characteristics.
A moveable feast—economic substance and holding entities
Authors: Fife Ashley 
Published: November 2019

Abstract
The economic substance requirements that the European Union insisted that a number of international financial centres introduce may be the most complex and far-reaching of international initiatives to impact on those jurisdictions in recent years. The requirements extend beyond due diligence, reporting and exchange of information to potentially impact on the way in which entities resource and carry on business in or from those jurisdictions. However, not all sectors of international business are impacted in the same way or to the same extent. This article considers certain aspects of the economic substance requirements relevant to private client structures, with a particular focus on the impact on holding entities. The treatment of holding entities under economic substance legislation in a number of C.2.2 jurisdictions may not be settled and this article explores how it may evolve.
Keeping time in the lamina terminalis: Novel oscillator properties of forebrain sensory circumventricular organs
Authors: Northeast Rebecca C. , Chrobok Lukasz , Hughes Alun T. L. , Petit Cheryl , Piggins Hugh D. 
Published: November 2019

AbstractDrinking behavior and osmotic regulatory mechanisms exhibit clear daily variation which is necessary for achieving the homeostatic osmolality. In mammals, the master clock in the brain's suprachiasmatic nuclei has long been held as the main driver of circadian (24 h) rhythms in physiology and behavior. However, rhythmic clock gene expression in other brain sites raises the possibility of local circadian control of neural activity and function. The subfornical organ (SFO) and the organum vasculosum laminae terminalis (OVLT) are two sensory circumventricular organs (sCVOs) that play key roles in the central control of thirst and water homeostasis, but the extent to which they are subject to intrinsic circadian control remains undefined. Using a combination of ex vivo bioluminescence and in vivo gene expression, we report for the first time that the SFO contains an unexpectedly robust autonomous clock with unusual spatiotemporal characteristics in core and noncore clock gene expression. Furthermore, putative single‐cell oscillators in the SFO and OVLT are strongly rhythmic and require action potential‐dependent communication to maintain synchrony. Our results reveal that these thirst‐controlling sCVOs possess intrinsic circadian timekeeping properties and raise the possibility that these contribute to daily regulation of drinking behavior.
Zebrafish prmt7 negatively regulates antiviral responses by suppressing the retinoic acid‐inducible gene‐I‐like receptor signaling
Authors: Zhu Junji , Liu Xing , Cai Xiaolian , Ouyang Gang , Fan Sijia , Wang Jing , Xiao Wuhan 
Published: November 2019

AbstractArginine methylation is a post‐translational modification in histone and nonhistone proteins that can affect numerous cellular activities. Protein arginine methyltransferase 7 (Prmt7), a type III arginine methyltransferase, catalyzes the formation of stable monomethylarginines of histones. The role of PRMT7 in virus‐induced innate immunity signaling, however, remains largely unknown. We demonstrate that zebrafish prmt7 could be inhibited by spring viremia of carp virus (SVCV) and grass carp reovirus (GCRV) infection. The overexpression of prmt7 suppresses cellular antiviral responses that are partially dependent on the arginine methyltransferase activity of prmt7. Consistently, prmt7‐null zebrafish were more resistant to SVCV or GCRV infection, exhibiting enhanced expression of key antiviral genes and fewer necrotic cells in the liver and kidney upon viral infection. Furthermore, we established a zebrafish model to investigate grass carp hemorrhagic disease. Our findings suggest that by suppressing the RIG‐I‐like receptors signaling, zebrafish prmt7 negatively regulates antiviral responses, indicating the vital role of prmt7 and its arginine methyltransferase activity in innate immunity.
Update on exhaled breath condensate analyses in occupational disease
Authors: Maestrelli Piero , Mason Paola , Guarnieri Gabriella 
Published: November 2019

Purpose of review
The present work represents an update of the review published in this journal by Corradi et al., regarding the use of exhaled breath condensate (EBC) to investigate occupational lung diseases.

Recent findings
The relevant literature was searched in the Medline database, assessed through PubMed using key terms such as ‘breath AND condensate AND occupational’. Eleven pertinent publications were retrieved between January 2018 and October 2019. One article only was related to occupational allergy, and the conclusion is that EBC hydrogen peroxide is not an useful marker in laboratory animal allergy. The biomarkers of exposure most often assessed with EBC are metals. However, it is controversial whether this approach has any advantage over the conventional environmental monitoring. The biomarkers of effect studied by the majority of investigations were those related to oxidative stress. They appear consistently elevated upon occupational exposures to various agents, including welding fumes, crystalline silica, nanomaterials and chemicals.

Summary
Although EBC represent a suitable tool to sample airway lining fluid in a noninvasive manner, it remains a niche approach to the investigation of occupational diseases. The confounding influence of EBC dilution should be better addressed in the expression of the results.
Internally Fabricated Chimera Anterolateral Thigh-Amputate Flaps for Metachronous Reconstruction
Authors: Osinga Rik , Lo Steven John 
Published: November 2019

Background:
The chimera flap is a versatile and exciting tissue composition for the reconstruction of complex tissue defects.

Methods:
Here, we present 2 cases of internally fabricated anterolateral thigh (ALT)-amputate chimera flaps for metachronous transfer.

Results:
A 22-year-old man (case 1) developed extended soft tissue necrosis in both legs following meningococcal septicemia. Before unilateral amputation, a fasciocutaneous flap based on the posterior tibial artery perforators was saved and ectopically implanted onto the ipsilateral thigh, creating an ALT-amputate chimera flap. Three months later, it was shown that the islanded ALT-amputate chimera flap remained well vascularized on either pedicle alone. Thus, a “true chimera circulation” over the scar between the 2 flaps must have developed. Subsequent free tissue transfer to the remaining right lower leg was performed successfully with uneventful healing. A 57-year-old fisherman (case 2) suffered a traumatic avulsion of his left thumb, which was ectopically replanted onto the contralateral thigh, creating an ALT-amputate chimera flap. After 3 months, the flap was raised and orthotopically replanted successfully with arthrodesis through the metacarpophalangeal joint. The previously coapted radial digital lateral femoral cutaneous nerve was coapted in the palm, and an flexor digitorum superficialis (FDS) ring transfer was performed for flexor pollicis longus (FPL) reconstruction.

Conclusions:
To the best of our knowledge, these are the first case reports using the descending branch of the lateral circumflex femoral artery system for (1) temporary ectopic implantation of a thumb and (2) temporary implantation of fasciocutaneous tissue based on posterior tibial artery perforators just before below knee amputation to reconstruct the contralateral leg.
Prescribing Trends of Topical Glaucoma Medications in Australia From 2001 to 2017
Authors: Perera Nayomi , Pinnuck Brigid C. , Jamieson Michael P.H. , Ling Damien , Williams Michael , Chen Oliver 
Published: November 2019

Precis:
As new glaucoma treatments arise, including minimally invasive glaucoma surgeries and new classes of glaucoma medications, it is important to examine the prescription trends of current topical glaucoma medications and how they may change.

Purpose:
To determine the prescribing trends of topical glaucoma medications in Australia from 2001 to 2017.

Methods and Analysis:
Pharmaceutical Benefits Scheme (PBS) item numbers were used to determine glaucoma medication prescribing rates from 2001 to 2017. All data were adjusted for population (/100,000) as per the Australian Bureau of Statistics (ABS) population data.

Results:
Overall prescription rates for glaucoma medications ranged between 67,904 and 86,936 per 100,000 from 2001 to 2017. An upward trend was noted from 2001 to 2015, with the exception of a notable decline in 2013 by 14.7%, before then increasing by 13.7% in 2014. After 2015, prescribing rates were seen to decrease over the subsequent years in the study period. Latanoprost remained the most prescribed medication and prostaglandin the most prescribed class. Prescribing rates of single-agent beta-blockers were noted to decrease during the 17-year period, particularly with the introduction of combination agents, which note an upward trend. Brinzolamide/brimonidine has increased by 50.0% from 2016 to 2017.

Conclusions:
Total rates of prescriptions have remained relatively stable from 2001 to 2017. The number of medications prescribed when considering combination agents separately was seen to be increasing from 2001 to 2015. From 2015 to 2017, a downward trend was noted in the number of medications prescribed. Prostaglandins remain the most prescribed class throughout the study period.
The Effect of Smoking on Mitochondrial Biogenesis in Patients With Graves Ophthalmopathy
Authors: Yuksel Nilay , Yaman Derya , Tugce Pasaoglu Ozge , Pasaoglu Hatice 
Published: November 2019

Purpose:To evaluate the effects of cigarette smoking on oxidative stress (OS) and mitochondrial biogenesis related parameters in patients Graves Ophthalmopathy (GO).Methods:Patients with moderate-to-severe GO according to the European Group on Graves Orbitopathy (EUGOGO) criteria were prospectively enrolled in this study. Age- and sex-matched healthy volunteers who applied to outpatient clinic due to refractive problems consisted the control group. Participants were divided into 4 groups based on their diagnosis and smoking status: group 1 (n = 30) smoker GO patients, group 2 (n = 30) nonsmoker GO patients, group 3 (n = 30) smoker healthy controls, and group 4 (n = 30) nonsmoker healthy controls. In the sera, total antioxidant status, total oxidant status and OS index values, peroxisome proliferator-activated receptor-γ coactivator 1-α, mitochondrial transcriptional factor A levels, and paraoxonase-1 enzyme activity were evaluated.Results:Total oxidant status and OS index values were the highest in group 1 compared to other groups (p= 0.031,p= 0.042; respectively). There was no statistically significant difference in total antioxidant status and peroxisome proliferator-activated receptor-γ coactivator 1α levels among the groups (p= 0.521,p= 0.388; respectively). Paraoxonase-1 enzyme activity was the lowest in group 1 and highest in group 4 (p= 0.024). The levels of mitochondrial transcriptional factor A was the lowest in group 1 compared to other groups (p= 0.012).Conclusions:Cigarette smoking in GO patients seems to be a risk factor that increases OS, and therefore, it may have an unfavorable impact on the mitochondrial biogenesis.
Development and Validation of a Questionnaire to Measure Psychosocial Work Stressors in Modern Working Environments
Authors: Diebig Mathias , Dragano Nico , Körner Ulrike , Lunau Thorsten , Wulf Ines Catharina , Angerer Peter 
Published: November 2019

Objective:
The rapid development of technology is changing working conditions of many employees. With this, appropriate measurement instruments to capture work-related psychosocial risks to create healthy working conditions are becoming more and more important. Therefore, we developed and validated a questionnaire to assess stressors in work settings which are characterized by a high degree of digitization.

Method:
The validation was based on two independent studies with data collected in four subsamples. All participants were asked about their working conditions and health-related topics using online questionnaires.

Results:
The resulting 16-item questionnaire consists of five scales: work load, boundary permeability, participation, leader support, and usability.

Conclusions:
The results show that the five identified stressors showed acceptable to good values with regard to reliability (internal consistencies, test-retest reliabilities, and interrater agreement) as well as (convergent and concurrent) validity.
Incidental Effect of Long-Term Tacrolimus Treatment on Sporadic Vestibular Schwannoma Volume Shrinkage and Clinical Improvement
Authors: Delmas Justine , Varoquaux Arthur , Troude Lucas , Salburgo Florent , Lavieille Jean-Pierre , Montava Marion 
Published: November 2019

Objective:
We describe the effect of long-term tacrolimus delivery on sporadic vestibular schwannoma (VS).

Patient:
A 48-year-old woman who was diagnosed a right VS.

Intervention:
Long-term tacrolimus delivery following liver transplant.

Main Outcome Measures:
Clinical examination, audiometric test, and gadolinium-contrasted magnetic resonance imaging.

Results:
During the reported follow-up period, the patient felt hearing improvement especially in noisy environment. This was consistent with a clear audiometric improvement. Over a 26 months follow-up period, we noticed a 50% volume regression and a 40% decrease in the intensity of enhancement of the tumor after gadolinium injection.

Conclusion:
Tacrolimus, an immunosuppressant used to prevent rejection in organ transplant, could lead to VS volume shrinkage and hearing improvement. Tacrolimus could be an interesting new therapeutic weapon, especially for VS in Neurofibromatosis type 2.
Effects of Age at Auditory Brainstem Implantation: Impact on Auditory Perception, Language Development, Speech Intelligibility
Authors: Aslan Filiz , Ozkan Hilal Burcu , Yücel Esra , Sennaroğlu Gonca , Bilginer Burçak , Sennaroğlu Levent 
Published: November 2019

Objective:
To study the effect of age at auditory brainstem implant (ABI) surgery on auditory perception, language, and speech intelligibility.

Study Design:
Retrospective single cohort design.

Setting:
Tertiary referral center.

Patients:
In this study, 30 pediatric ABI users with no significant developmental issues were included. Participants were divided into two groups, according to age at surgery (Early Group: < 3 yr old [n = 15], Late Group: ≥ 3 yr old [n = 15]). Groups were matched by duration of ABI use and participants were evaluated after 5 years (±1 yr) experience with their device. The mean age at ABI surgery was 22.27 (ranged ± 6.5) months in the early group, 45.53 (ranged ± 7.9) months in the late group.

Intervention(s):
Retrosigmoid craniotomy and ABI placement.

Main Outcome Measure(s):
Auditory perception skills were evaluated using the Meaningful Auditory Integration Scale and Categories of Auditory Performance from the Children's Auditory Perception Test Battery. We used a closed-set pattern perception subtest, a closed-set word identification subtest, and an open-set sentence recognition subtest. Language performance was assessed with the Test of Early Language Development and Speech Intelligibility Rating, which was administered in a quiet room.

Results:
In this study, the results demonstrated that the Early Group's auditory perception performance was better than the Late Group after 5 years of ABI use, when children had no additional needs (U = 12, p < 0.001). Speech intelligibility was the most challenging skill to develop, in both groups. Due to multiple regression analysis, we found that auditory perception categories can be estimated with speech intelligibility scores, pattern perception scores, receptive language scores, and age at ABI surgery variables in ABI users with no additional handicaps.

Conclusions:
ABI is a viable option to provide auditory sensations for children with cochlear anomalies. ABI surgery under age 3 is associated with improved auditory perception and language development compared with older users.