bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-Life Management Pathways for Chronic Peripheral Neuropathic Pain at Tertiary Pain Clinics in France
Authors: Perrot Serge , Pickering Gisèle , Lantéri-Minet Michel , Attal, MD, PhD Nadine 
Published: January 2021

AbstractObjectivePeripheral neuropathic pain (PNP) represents a major public health issue. Severe or refractory cases warrant tertiary multidisciplinary management, but little information is available about real-life care pathways. The primary objective of this cross-sectional, observational study was to investigate the pathways of patients with PNP consulting for the first time or followed for less than 1 year in French tertiary specialized pain clinics.MethodsPNP was diagnosed with the NeuPSIG algorithm. Data collected included demographics, pain characteristics, and details of management before and after the study visit (e.g., drug and non-drug treatment, nature of medical visits), as well as time to referral to a pain clinic and time to a diagnosis of PNP. Factors associated with delayed referral or diagnosis were analyzed with multivariate analysis.ResultsA total of 404 patients with PNP (age 55.8 ± 15.6 years, 60.3% females, 78.3% retired or unemployed, pain duration 43.4 ± 68.9 months) were enrolled by 84 pain specialists. Pain affected mainly the lower limbs (53.5%) and was predominantly related to surgery or trauma (59.4%). Primary care management was characterized by a high proportion of conventional analgesics (60.7%). Time to referral to a pain clinic was 43.4 ± 68.9 months since pain onset and 20.1 ± 39.4 months since the diagnosis of PNP. Delayed referral to a pain clinic was independently predicted by the clinical specialty of the referring doctor and by male gender.ConclusionsThis study highlights the need for accessible guidance for non–pain specialists to improve their diagnostic and management skills and for faster referral of patients with PNP to tertiary pain clinics.
Opioid Tapering/Detoxification Protocols, A Compendium: Narrative Review
Authors: Fishbain David A 
Published: January 2021

AbstractObjectivesThe opioid epidemic has put pressure on clinicians to taper their chronic pain patients (CPPs) from opioids. This has resulted in rapid or forced tapers and opioid discontinuation. Partially responsible is lack of information on how to taper (tapering protocols).The objectives of this narrative review were then the following: compile all the published opioid tapering/detoxification protocols from the pain/drug rehabilitation/psychiatric literature whether for inpatient or outpatient use; organize these into general types; compare the types for advantages/disadvantages for use by a clinician in an outpatient setting; and answer some commonly asked questions relating to opioid tapering.MethodsRelevant references were identified by a search strategy utilizing the terms tapering, tapering protocols, detoxification, detoxification protocols, withdrawal, dependence, addiction, and drug rehabilitation. These were explored with the term opioids. Identified abstract were reviewed for any study relating to the objectives of this review. Those studies were then included in this review. As this is a narrative review, no quality ratings of these references were performed.ResultsOf 1,922 abstracts identified by this search strategy, 301 were reviewed in detail for potential inclusion. Of these, 104 were utilized in this review. Nine types of opioid tapering protocols were identified and compared in tabular form. Twenty-two questions in reference to opioid tapering were addressed.ConclusionsBased on this review, the protocol utilizing the opioid of current use is the simplest to use as it requires no rotation to another opioid and thereby avoids rotation errors. It also has behavior advantages.
Similar biologic drug response regardless of radiographic status in axial spondyloarthritis: data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis registry
Authors: Michelena Xabier , Zhao Sizheng Steven , Dubash Sayam , Dean Linda E , Jones Gareth T , Marzo-Ortega Helena 
Published: January 2021

Abstract

Objective
To describe the baseline characteristics, biologic DMARD (bDMARD) response and drug survival of axial SpA (axSpA) patients in the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) according to radiographic status.

Methods
The BSRBR-AS is a national prospective cohort including axSpA participants classified according to the Assessment of SpondyloArthritis international Society criteria. In this analysis, baseline data of patients starting bDMARDs were compared. Ankylosing Spondylitis Disease Activity Scores (ASDASs) for low disease status, clinically important improvement (CII) and major improvement (MI) at 1 year were used to assess treatment response. Cox proportional hazards analysis was performed after adjusting for clinically relevant confounders.

Results
A total of 1145 axSpA patients were included. Higher male prevalence, older age and longer disease duration were seen in the radiographic axSpA (r-axSpA) subgroup. Based on a complete case analysis (290 patients), two-thirds of patients achieved an ASDAS low disease state at 1 year regardless of radiographic status [non-radiographic axSpA (nr-axSpA) 64.2% vs r-axSpA 66.1]. No statistically significant differences were seen between the subgroups in attaining ASDAS CII (nr-axSpA 50.7% vs r-axSpA 44.7%) or MI (nr-axSpA 20% vs r-axSpA 18.7%). Drug survival probability curves were similar for both subgroups and the hazard ratio for nr-axSpA/axSpA was 0.94 (95% CI 0.69, 1.28) when adjusted for sex, age, baseline ASDAS with CRP, smoking status, disease duration, HLA-B27 and prescribed biologic.

Conclusions
Although there appeared to be some differences in the baseline characteristics when exploring this cohort according to radiographic status, which are likely related to the natural history of the disease, the level of biologic response and drug survival was comparable between nr-axSpA and r-axSpA.
Association of venous thromboembolic events with skin, pulmonary and kidney involvement in ANCA-associated vasculitis: a multinational study
Authors: Moiseev Sergey , Kronbichler Andreas , Makarov Egor , Bulanov Nikolay , Crnogorac Matija , Direskeneli Haner , Galesic Kresimir , Gazel Ummugulsum , Geetha Duvuru , Guillevin Loic , Hrušková Zdenka , Little Mark A , Ahmed Adeel , McAdoo Stephen P , Mohammad Aladdin J , Moran Sarah , Novikov Pavel , Pusey Charles D , Rahmattulla Chinar , Satrapová Veronika , Silva Joana , Terrier Benjamin , Tesař Vladimír , Westman Kerstin , Jayne David R W 
Published: January 2021

Abstract

Objective
To investigate the occurrence of venous thromboembolic events (VTE) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, Turkey, Russia, UK and North America.

Methods
Patients with a definite diagnosis of AAV who were followed for at least 3 months and had sufficient documentation were included. Data on VTE, including either deep vein thrombosis or pulmonary embolism, were collected retrospectively from tertiary vasculitis centres. Univariate and multivariate regression models were used to estimate odds ratios (ORs) and 95% CIs.

Results
Over a median follow-up of 63 (interquartile range: 29, 101) months, VTE occurred in 278 (9.7%) of 2869 AAV patients with a similar frequency across different countries (from 6.3% to 13.7%), and AAV subtype [granulomatosis with polyangiitis: 9.8% (95% CI: 8.3, 11.6%); microscopic polyangiitis: 9.6% (95% CI: 7.9, 11.4%); and eosinophilic granulomatosis with polyangiitis: 9.8% (95% CI: 7.0, 13.3%)]. Most VTE (65.6%) were reported in the first-year post-diagnosis. Multiple factor logistic regression analysis adjusted for sex and age showed that skin (OR 1.71, 95% CI: 1.01, 2.92), pulmonary (OR 1.78, 95% CI: 1.04, 3.14) and kidney [eGFR 15–60 ml/min/1.73 m2, OR 2.86 (95% CI: 1.27, 6.47); eGFR &lt;15 ml/min/1.73 m2, OR 6.71 (95% CI: 2.94, 15.33)] involvement were independent variables associated with a higher occurrence of VTE.

Conclusion
Two-thirds of VTE occurred during the initial phase of active disease. We confirmed previous findings from smaller studies that a decrease in kidney function, skin involvement and pulmonary disease are independently associated with VTE.
3D-Printed Ostomy Flange Stabilizer
Authors: Cosman Ilan E. , Guillou Daniel T. , Cosman Bard C. 
Published: January 2021

BACKGROUND:
One of the coauthors with tetraplegia (quadriplegia) and a colostomy invented an ostomy flange stabilizer to act as a temporary backplate and aid in pouch changes.

DEVICE DEVELOPMENT:
In an interactive design process, a 3D-printed ostomy flange stabilizer device was created. The resulting device can be adapted to 3 standard stoma appliance sizes. The stabilizer is reversible, allowing right- and left-handed people to use it on right- or left-sided stomas. Anyone with a 3D printer can print this device from an open-access Web site.

CONCLUSION:
This device may be of use to many with ostomies and especially those with impaired dexterity.
A 3D-printed ostomy flange stabilizer is described. 3D printing allows patient inventions to be disseminated without commercialization.
Heterozygous mutation ofVegfr3decreases renal lymphatics but is dispensable for renal function
Authors: Liu Hao , Hiremath Chitkale , Patterson Quinten , Vora Saumya , Shang Zhiguo , Jamieson Andrew R. , Fiolka Reto , Dean Kevin M. , Dellinger Michael T. , Marciano Denise K. 
Published: January 2021

ABSTRACTBackgroundLymphatic abnormalities are observed in several types of kidney disease, but the relationship between the renal lymphatic system and renal function is unclear. The discovery of lymphatic-specific proteins, advances in microscopy, and available genetic mouse models provide the tools to help elucidate the role of renal lymphatics in physiology and disease.MethodsWe utilized a mouse model containing a missense mutation inVegfr3(dubbedChy) that abrogates its kinase ability.Vegfr3Chy/+mice were examined for developmental abnormalities and kidney-specific outcomes. Control andVegfr3Chy/+mice were subjected to cisplatin-mediated injury. We characterized renal lymphatics using a combination of tissue clearing, light-sheet microscopy and computational analyses.ResultsIn the kidney, we found Vegfr3 is expressed not only in lymphatic vessels, but also various blood vessels.Vegfr3Chy/+mice had severely reduced renal lymphatics with 100% penetrance, but we found no abnormalities in blood pressure, renal function and histology. Similarly, there was no difference in the degree of renal injury after cisplatin, althoughVegfr3Chy/+mice developed more perivascular inflammation by histology. Control mice treated with cisplatin had a measurable increase in cortical lymphatic density despite no change in cortical lymphatic volume and length.ConclusionsWe demonstrate that Vegfr3 is required for development of renal lymphatics, but a reduction in lymphatic density does not alter renal function and induces only modest histological changes after injury. Our data suggests that an increase in lymphatic density after cisplatin injury may reflect the loss of cortical volume associated with chronic kidney disease rather than growth of lymphatic vessels.SIGNIFICANCE STATEMENTDefects in renal lymphatics occur in various kidney diseases, but their role in maintaining kidney structure and function is unknown. We combine tissue clearing, light-sheet microscopy and computational analysis to characterize lymphatics and find that mice with a heterozygous mutation inVegfr3(Vegfr3Chy/+) have severely reduced renal lymphatics. Strikingly, these mice have indistinguishable renal function and histology compared with controls. Even after cisplatin injury, there are no differences in renal function, althoughVegfr3Chy/+mice developed more perivascular inflammation. Our data present a novel method of lymphatic quantification and suggest that a normal complement of renal lymphatics is dispensable for renal structure and function.
Imaging-based patient inclusion model improves clinical trial performance
Authors: Tomaszewski Michal R. , Fan Shuxuan , Garcia Alberto , Qi Jin , Kim Youngchul , Gatenby Robert A. , Schabath Matthew B. , Tap William D. , Reinke Denise K. , Makanji Rikesh J , Reed Damon R. , Gillies Robert J. 
Published: January 2021

AbstractPurposeSuccess of new cancer therapies relies strongly on effective selection of the target patient populations. We hypothesize that computational analysis of imaging data can be used for patient enrichment in clinical trials and hence aimed to establish the appropriate framework for this analysis.MethodsThis was tested among soft-tissue sarcoma (STS) patients accrued into a randomized clinical trial (SARC021) that evaluated the efficacy of evofosfamide (Evo), a hypoxia activated prodrug, in combination with doxorubicin (Dox). Notably, SARC021 failed to meet its overall survival (OS) objective. We tested whether a radiomic biomarker-driven inclusion/exclusion criterion could have been used to result in a significant treatment benefit of the Evo+Dox combination compared to Dox monotherapy. 164 radiomics features were extracted from 303 SARC021 patients with lung metastases, divided into training and test sets.ResultsA single radiomics feature, Short Run Emphasis, was identified as the most informative. Combined into a model along with histological classification and smoking history, an enriched subset (42%) of patients had longer OS in Evo+Dox vs. Dox groups [p=0.01, Hazard Ratio (HR) =0.57 (0.36-0.90)]. Applying the same model and threshold value in an independent test set confirmed the significant survival difference [p=0.002, HR=0.29 (0.13-0.63)], identifying patients most likely to benefit from doxorubicin alone.ConclusionThe study presents a first of its kind clinical-radiomic approach for patient enrichment in clinical trials. We show that, had an appropriate model been used for selective patient inclusion, SARC021 trial could have met its primary survival objective for patients with metastatic STS.
NanoMethViz: an R/Bioconductor package for visualizing long-read methylation data
Authors: Su Shian , Gouil Quentin , Blewitt Marnie E. , Cook Dianne , Hickey Peter F. , Ritchie Matthew E. 
Published: January 2021

AbstractMotivationA key benefit of long-read nanopore sequencing technology is the ability to detect modified DNA bases, such as 5-methylcytosine. Tools for effective visualization of data generated by this platform to assess changes in methylation profiles between samples from different experimental groups remains a challenge.ResultsTo make visualization of methylation changes more straightforward, we developed the R/Bioconductor packageNanoMethViz. Our software can handle methylation calls generated from a range of different methylation callers and manages large datasets using a compressed data format. To fully explore the methylation patterns in a dataset,NanoMethVizallows plotting of data at various resolutions. At the sample-level, we use multidimensional scaling to look at the relationships between methylation profiles in an unsupervised way. We visualize methylation profiles of classes of features such as genes or CpG islands by scaling them to relative positions and aggregating their profiles. At the finest resolution, we visualize methylation patterns across individual reads along the genome using thespaghetti plot,allowing users to explore particular genes or genomic regions of interest.In summary, our software makes the handling of methylation signal more convenient, expands upon the visualization options for nanopore data and works seamlessly with existing methylation analysis tools available in the Bioconductor project. Our software is available athttps://bioconductor.org/packages/NanoMethViz.
Homo-and heterofermentative lactobacilli are differently affected by lignocellulosic inhibitory compounds
Authors: Giacon Thamiris Guerra , de Gois e Cunha Gabriel Caetano , Eliodório Kevy Pontes , de Souza Oliveira Ricardo Pinheiro , Basso Thiago Olitta 
Published: January 2021

AbstractSecond generation (2G) ethanol is produced through the use of lignocellulosic biomass. However, the pretreatment processes generates a variety of molecules (furan derivatives, phenolic compounds and organic acids) that act as inhibitors of microbial metabolism, and thus reduce the efficiency of the fermentation step in this process. In this context, the present study aimed to investigate the effect of furan derivatives on the physiology of lactic acid bacteria (LAB) strains that are potential contaminants of ethanol production. Homofermentative and heterofermentative strains of laboratory LAB and isolated from first generation ethanol fermentation were used. LAB strains were challenge to grow in the presence of furfural and hydroxymethyylfurfural (HMF). We found that the effect of HMF and furfural on the growth rate of LAB is dependent of the metabolic type, and growth kinetics in the presence of these compounds is enhanced for heterofermentative LAB, whereas is inhibitory to homofermentative LAB. Sugar consumption and product formation were also enhanced in the presence of furaldehydes in heterofermentative LAB, that displayed an effective detoxification kinetics when compared to the homofermentative LAB. This knowledge is important because LAB can be explored both within the scope of bio-detoxification, being applied before the fermentation.Key points‐Heterofermentative LAB presented the ability to decrease the concentrations of furfural and HMF‐LAB can be used in the bio-detoxification to remove the inhibitors before fermentations‐The presence of furan derivatives had a growth stimulus observed in heterofermentative LAB
“Less is more”: a dose-response account of intranasal oxytocin pharmacodynamics in the human brain
Authors: Martins Daniel , Broadmann Katja , Veronese Mattia , Dipasquale Ottavia , Mazibuko Ndaba , Schuschnig Uwe , Zelaya Fernando , Fotopoulou Aikaterini , Paloyelis Yannis 
Published: January 2021

AbstractIntranasal oxytocin is receiving increasing research attention as a potential treatment for several brain disorders due to promising preclinical results. However, translating these findings to humans has been hampered by remaining uncertainties about its pharmacodynamics and the methods used to probe its effects in the human brain. Using a dose-response design (9, 18 and 36 IU) and a novel administration device, we demonstrate that oxytocin-induced physiological changes in the amygdala at rest, a key-hub of the brain oxytocin system, follow a dose-response curve with maximal effects for lower doses. Yet, the effects of oxytocin vary by amygdala subdivision, highlighting the need to qualify dose-response curves within subregion. We further link physiological changes with the density of the oxytocin receptor gene mRNA across brain regions, strengthening our confidence in intranasal oxytocin as a valid approach to engage central targets. Finally, we demonstrate that intranasal oxytocin does not disrupt cerebrovascular reactivity; the absence of major vascular confounds corroborates the validity of haemodynamic neuroimaging to probe the effects of intranasal oxytocin in the human brain.
Forebrain Shh overexpression improves cognitive function in a Down syndrome mouse model and euploid littermates
Authors: Gao Feng J. , Klinedinst Donna , Fernandez Fabian-Xosé , Cheng Bei , Savonenko Alena , Devenney Benjamin , Li Yicong , Wu Dan , Pomper Martin G. , Reeves Roger H. 
Published: January 2021

SummaryPeople with Down syndrome (DS) have intellectual disability, early-onset dementia, and cerebellar hypoplasia. Trisomic cerebellar granule cell precursors from Ts65Dn, a mouse model of DS, had a deficit in mitogenic response to Sonic hedgehog (Shh)in vitro, and newborn Ts65Dn mice received a single subcutaneous injection of the Shh signaling agonist SAG had normalized cerebellar morphology and improved spatial learning and hippocampal synaptic plasticity at adult. However, cognitive effects of Shh overexpressionin vivoand where SAG acts to improve cognitive outcomes of trisomy are unknown. Here, we created an inducible human Shh (hShh) knock-in mouse, TRE-bi-hShh-Zsgreen1 (TRE-hShh), expressing dually-lipidated Shh-Np in the presence of transactivator (tTA). Double transgenic mice, Camk2a-tTA;TRE-hShh (Camk2a-hShh) and Pcp2-tTA;TRE-hShh (Pcp2-hShh), increased Shh signaling in forebrain and cerebellum, respectively. Forebrain Shh overexpression normalized hyperactivity, and spatial learning and memory deficits in 3-month-old Ts65Dn, while Shh overexpression in cerebellum had no effect. Further, Camk2a-hShh delayed early-onset severe cognitive impairment in 7-month-old Ts65Dn and enhanced spatial cognition in euploid (Eu) and showed no effect on the longevity of Eu or Ts65Dn, and MRI demonstrated that Pcp2-hShh mitigated disproportionately small cerebellum in Ts65Dn. Finally, Ts65Dn at postnatal day 6 had reduced Gli1 levels in hippocampus and cerebellum, which could be at least partially rescued by Camk2a-hShh and Pcp2-hShh, respectively. Our findings suggest restoration of impaired Shh signaling in forebrain from the perinatal and early postnatal period improves cognitive function.
The paradox of accounting for cultural heritage: a longitudinal study on the financial reporting of heritage assets of major Australian public cultural institutions (1992–2019)
Authors: Ferri Paolo , Sidaway Shannon I.L. , Carnegie Garry D. 
Published: January 2021

PurposeThe monetary valuation of cultural heritage of a selection of 16 major public, not-for-profit Australian cultural institutions is examined over a period of almost three decades (1992–2019) to understand how they have responded to the paradoxical tensions of heritage valuation for financial reporting purposes.Design/methodology/approachAccounting for cultural heritage is an intrinsically paradoxical practice; it involves a conflict of two opposite ways of attributing value: the traditional accounting and the heritage professionals (or curatorial) approaches. In analysing the annual reports and other documentary sources through qualitative content analysis, the study explores how different actors responded to the conceptual and technical contradictions posed by the monetary valuation of “heritage assets”, the accounting phraseology of accounting standards.FindingsFour phases emerge from the analysis undertaken of the empirical material, each characterised by a distinctive nature of the paradox, the institutional responses discerned and the outcomes. Although a persisting heterogeneity in the practice of accounting for cultural heritage is evident, responses by cultural institutions are shown to have minimised, so far, the negative impacts of monetary valuation in terms of commercialisation of deaccessioning decisions and distorted accountability.Originality/valueIn applying the theoretical lens of paradox theory in the context of the financial reporting of heritage, as assets, the study enhances an understanding of the challenges and responses by major public cultural institutions in a country that has led this development globally, providing insights to accounting standard setters arising from the accounting practices observed.