bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating dermatology education and training
Authors: Byrne-Davis Lucie , Cohen Stuart N. , Turner Rebecca R. 
Published: September 2022

Abstract
The purpose of education and training in dermatology ranges from increasing knowledge and skills to improving confidence or enhancing patient outcomes. Specification of the purpose of the education and training is vital so that evaluation can be aligned to purpose, and thus provide evidence on effectiveness. Further, the quality and quality improvement of education and training can be enhanced by a careful specification of how they are expected to achieve their purpose. Multiple theories and methods can be used to evaluate both the process and the outcome of education and training. In this paper, we summarize some of these and focus particularly on the use of behavioural science to evaluate education and training. We illustrate these theories and methods with an example in dermatology.
Myelin oligodendrocyte glycoprotein antibody‐associated disease presenting as recurrent acute disseminated encephalomyelitis: Case report of the youngest Mexican patient in the literature
Authors: García‐Estrada Christian , Gómez‐Figueroa Enrique , Morelos‐Cisneros Juan Pablo , Deras‐Martinez Alondra 
Published: September 2022

AbstractBackgroundMyelin oligodendrocyte glycoprotein antibody‐associated disease myelin oligodendrocyte glycoprotein antibody‐associated disease is an emerging demyelinating condition distinct from neuromyelitis optica spectrum disorder and multiple sclerosis affecting both children and adults with a spectrum of clinical manifestations ranging from optic neuritis, myelitis and acute disseminated encephalomyelitis.Case reportWe describe the case of a 2 year‐old girl diagnosed with myelin oligodendrocyte glycoprotein antibody‐associated disease presenting as recurrent acute disseminated encephalomyelitis who showed suppression of disease activity after treatment with rituximab. This case represents the youngest Mexican patient with myelin oligodendrocyte glycoprotein antibody‐associated disease reported to date.ConclusionsInformation regarding the clinical presentation and evolution among different population could help to a better understanding of the presentation of this entity.
Headway and the remaining hurdles of mesenchymal stem cells therapy for bronchopulmonary dysplasia
Authors: Tang Eireen , Zaidi Mariam , Lim Wen‐Huey , Govindasamy Vijayendran , Then Kong‐Yong , Then Khong‐Lek , Das Anjan Kumar , Cheong Soon‐Keng 
Published: September 2022

AbstractObjectivePreterm infants are at a high risk of developing BPD. Although progression in neonatal care has improved, BPD still causes significant morbidity and mortality, which can be attributed to the limited therapeutic choices for BPD. This review discusses the potential of MSC in treating BPD as well as their hurdles and possible solutions.Data SourcesThe search for data was not limited to any sites but was mostly performed on all clinical trials available in ClinicalTrials.gov as well as on PubMed by applying the following keywords: lung injury, preterm, inflammation, neonatal, bronchopulmonary dysplasia and mesenchymal stem cells.Study SelectionsThe articles chosen for this review were collectively determined to be relevant and appropriate in discussing MSC not only as a potential treatment strategy for curbing the incidence of BPD but also including insights on problems regarding MSC treatment for BPD.ResultsClinical trials regarding the use of MSC for BPD had good results but also illustrated insights on problems to be addressed in the future regarding the treatment strategy. Despite that, the clinical trials had mostly favourable reviews.ConclusionWith BPD existing as a constant threat and there being no permanent solutions, the idea of regenerative medicine such as MSC may prove to be a breakthrough strategy when it comes to treating BPD. The success in clinical trials led to the formulation of prospective MSC‐derived products such as PNEUMOSTEM®, and there is the possibility of a stem cell medication and permanent treatment for BPD in the near future.
State‐of‐the‐art therapies for Rett syndrome
Authors: Panayotis Nicolas , Ehinger Yann , Felix Marie Solenne , Roux Jean‐Christophe 
Published: September 2022

Rett syndrome (RTT) is an X‐linked neurogenetic disorder caused by mutations of the MECP2 (methyl‐CpG‐binding protein 2) gene. Over two decades of work established MeCP2 as a protein with pivotal roles in the regulation of the epigenome, neuronal physiology, synaptic maintenance, and behaviour. Given the genetic aetiology of RTT and the proof of concept of its reversal in a mouse model, considerable efforts have been made to design therapeutic approaches to re‐express MeCP2. By being at the forefront of the development of innovative gene therapies, research on RTT is of paramount importance for the treatment of monogenic neurological diseases. Here we discuss the recent advances and challenges of promising genetic strategies for the treatment of RTT including gene replacement therapies, gene/RNA editing strategies, and reactivation of the silenced X chromosome.What this paper adds

Recent advances shed light on the promises of gene replacement therapy with new vectors designed to control the levels of MeCP2 expression.

New developments in DNA/RNA editing approaches or reactivation of the silenced X chromosome open the possibility to re‐express the native MeCP2 locus at endogenous levels.

Current strategies still face limitations in transduction efficiency and future work is needed to improve brain delivery.
All‐cause and cardiorenal mortality in 6 million adults with and without type 2 diabetes: A comparative, trend analysis in Canada, Spain, and the UK
Authors: Ling Suping , Zaccardi Francesco , Vlacho Bogdan , Li Ping , Real Gatius Jordi , Mata‐Cases Manel , Franch‐Nadal Josep , Kosiborod Mikhail N. , Gillies Clare , Fenici Peter , Mauricio Dídac , Shah Baiju R. , Khunti Kamlesh 
Published: September 2022

AbstractAimsTo understand geographical and temporal patterns in the diabetes gap, the excess mortality risk associated with type 2 diabetes (T2D), in three high‐income countries.MethodsUsing databases from Canada (Ontario), Spain (Catalonia) and the UK (England), we harmonized the study design and the analytical strategy to extract information on subjects aged over 35 years with incident T2D between 1998 and 2018 matched to up to five subjects without diabetes. We used Poisson models to estimate age‐specific mortality trends by diabetes status and rate ratios and rate differences associated with T2D.ResultsIn more than 6 million people, 694 454 deaths occurred during a follow‐up of 52 million person‐years. Trends in all‐cause mortality rates differed between Ontario and England; yet, the diabetes gaps were very similar in recent years: in 2018, we estimated 1.3 (95% confidence interval: 0.8, 1.8) and 0.8 (0.2, 1.5) more deaths per 1000 person‐years in 50‐year‐old men with diabetes in Ontario and England, respectively, and 8.9 (6.1, 11.7) and 12.1 (9.1, 15.1) in 80‐year‐old men; between‐country differences were small also in women. In Catalonia, rate ratios comparing T2D with no diabetes in men in 2018 were 1.53 (1.11, 2.11) at 50 years old, 0.88 (0.72, 1.06) at 60 years old, 0.74 (0.60, 0.90) at 70 years old and 0.81 (0.66, 1.00) at 80 years old, indicating lower mortality rates in men with T2D from the age of 60 years; rates were similar in women with and without diabetes at all ages. The diabetes gaps in cardiorenal mortality mirrored those of all‐cause mortality: we observed consistent reductions in the proportions of cardiorenal deaths in subjects aged 80 years but variations in subjects aged ≤70 years, regardless of the presence of diabetes.ConclusionsBy reducing the confounding impact of epidemiological and analytical differences, this study showed geographical similarities and differences in the diabetes gap: an excess risk of all‐cause and cardiorenal mortality in subjects with T2D is still present in Ontario and England in recent years, particularly in elderly subjects. Conversely, there were very small gaps in young men with T2D or even lower mortality rates in older subjects with T2D in Catalonia.
Sodium‐glucose cotransporter‐2 inhibitors and the risk of gout in patients with type 2 diabetes mellitus: A propensity‐score‐matched, new‐user design study with an active comparator using the IQVIA Medical Research Data UK database
Authors: Subramanian Anuradhaa , Gokhale Krishna , Sainsbury Christopher , Nirantharakumar Krishnarajah , Toulis Konstantinos A. 
Published: September 2022

AbstractAimTo conduct a pharmacoepidemiological study to explore the association between sodium‐glucose cotransporter‐2 (SGLT2) inhibitors and gout in patients with type 2 diabetes mellitus (T2DM).Materials and MethodsA retrospective open cohort study using the IQVIA Medical Research Data UK database was performed between November 1, 2012 and December 31, 2018, estimating the risk of gout in patients with T2DM who were new users of SGLT2 inhibitors, compared to propensity‐score‐matched new users of dipeptidyl peptidase‐4 (DPP‐4) inhibitors.ResultsA total of 85 incident cases of gout were recorded over 30 389 person‐years of observation in 13 617 new users of SGLT2 inhibitors and 29 426 new users of DPP‐4 inhibitors. Crude incidence rates (IRs) per 1000 person‐years were 2.90 and 2.47 for new users of SGLT2 inhibitors and DPP‐4 inhibitors, respectively. The unadjusted hazard ratio (HR) was 1.18 (95% confidence interval [CI] 0.76‐1.83). The adjusted HR was 1.20 (95% CI 0.77‐1.86). In the at‐treatment analysis, crude IRs per 1000 person‐years were found to be 2.68 and 2.53 for SGLT2 inhibitor and DPP‐4 inhibitor users, respectively. In the adjusted model, the adjusted HR was 1.3 (95% CI 0.90‐2.29). Sensitivity analyses did not change the findings.ConclusionsIn this nationwide study, no difference in the incidence of gout was documented in patients treated with SGLT2 inhibitors compared to DPP‐4 inhibitor users. This neutral finding remained consistent in sensitivity analyses.
Comparison of imaging characteristics for mortality risk analysis between young and older acute aortic dissection patients
Authors: Zhou Ling , Chen Chen , Zheng Minjuan , Liu Lu , Xu Pan , Niu Yicui 
Published: September 2022

AbstractBackgroundThere are differences between young and older patients diagnosed with acute aortic dissection. We aimed to explore the differences in echocardiographic and computed tomography angiography (CTA) characteristics between the young and the older patients diagnosed with acute aortic dissection.MethodsThe data from 1220 patients with aortic dissection were collected. They were divided into the young and the older groups with the age threshold set at 45 years old. The basic information and imaging data were collected and compared between the two groups. Univariate regression was used to find the risk factors for mortality in each group.ResultsEchocardiographic results showed the proportion of left ventricular enlargement (young vs older, 39.9% vs 26.9%, p‐value <.001) and left ventricular dysfunction (22.3% vs 14.1%, p‐value ​​smaller than .001) in the young group was significantly higher. Although there is no statistically significant difference in mortality within 60 days after admission (12.0% vs 15.1%, p‐value equals to .164), the involvements of aortic branches were the risk factor for the mortality in the young group. For the older patients, the left ventricular remodeling detected by echocardiography (left atrial enlargement, ascending aortic dilation, aortic regurgitation) and decreased heart function were the risk factors for mortality.ConclusionsThe mortality of the young and the older groups with acute aortic dissection are comparable. The involvements of aortic branches were the mortality risk factors in the young patients while the structural and functional change of the left ventricle detected by echocardiography was the mortality risk factor for the older patients.
Allele PaLAR3B in root rot resistance locus does not influence the infection pressure by Heterobasidion parviporum through root contacts
Authors: Terhonen Eeva , Kashif Muhammad , Piri Tuula , Haapanen Matti , Hantula Jarkko 
Published: September 2022

AbstractThe most destructive root rot pathogen of Norway spruce (Picea abies) in Finland is Heterobasidion parviporum. After primary infection, this pathogen spreads from tree to tree through root contacts and eventually causes high levels of root and stem rot. Locus PaLAR3 has been associated with root rot resistance of Norway spruce, and higher resistance in Norway spruce against H. parviporum has been noted when trees have allele PaLAR3B instead of the more common PaLAR3A. In this study we tested if trees with homo‐ or heterozygous PaLAR3B allele can better resist the infection through root contacts. The study was established in 2018 in a site where spruce trees had grown at a dense spacing for 10 years. The 72 trees were cut down and a mixture of four H. parviporum strains was inoculated on the stumps. After 3 years, 459 trees surrounding the inoculated stumps were harvested and analysed. Based on the presence of conidiospores, forty percent (40%) of the trees were infected by H. parviporum. The homozygous PaLAR3B genotype was found only in 1% of the trees. There were no differences in infection rates between the genotypes AA and AB (or BB). Similarly, the distance from inoculated stump or the diameter of the tree did not influence the infection rate.
Not an ordinary bank but a great engine of state: The Bank of England and the British economy, 1694–1844
Authors: O'Brien Patrick K. , Palma Nuno 
Published: September 2022

AbstractFrom its foundation as a private corporation in 1694, the Bank of England extended large amounts of credit to support the British private economy and to support an increasingly centralised British state. The Bank helped the British state reach a position of geopolitical and economic hegemony in the international economic order. In this paper, we deploy recalibrated financial data to analyse an evolving trajectory of connections between the British economy, the state, and the Bank of England. We show how these connections contributed to form an effective and efficient fiscal–naval state and promote the development of a system of financial intermediation for the economy. This symbiotic relationship became stronger after 1793. The evidence that we consider here shows that although the Bank was nominally a private institution and profits were paid to its shareholders, it was playing a public role well before Bagehot's doctrine.
Third space workers in higher education in times of dislocated complexity
Authors: Livingston Kay , Ling Lorraine 
Published: September 2022

AbstractIn this article we examine the changing nature of the higher education workforce with specific reference to the increasing influence and importance of third space workers (e.g., blended learning designers, e‐learning developers, partnerships managers, associate tutors, learning technology specialists and communication and engagement officers). Discussing the contextual framework, we contend that the higher education context is uncertain and has taken on a disrupted character, generating a social condition that we term dislocated complexity. Through the lens of Giddens' Theory of Structuration, we analyse empirical data from two studies—one in Scotland and one in Australia—to shed light on how the workforce in higher education is changing. We illuminate the need for greater recognition of third‐space workers as part of a team alongside academic discipline experts in these times of dislocated complexity. We propose the term dislocated complexity as a means to describe the heightened state of complexity that exists in higher education systems in times of crisis, such as the COVID‐19 pandemic, and highlight the need for structural and policy changes.
JAK inhibition with ruxolitinib in relapsed or refractory classical Hodgkin lymphoma: Final results of a phase II, open label, multicentre clinical trial (JeRiCHO)
Authors: Gillessen Sarah , Pluetschow Annette , Vucinic Vladan , Ostermann Helmut , Kobe Carsten , Bröckelmann Paul J. , Böll Boris , Eichenauer Dennis A. , Heger Jan‐Michel , Borchmann Sven , Fuchs Michael , Borchmann Peter , Engert Andreas , von Tresckow Bastian 
Published: September 2022

AbstractObjectivesPatients with classical Hodgkin lymphoma (cHL) relapsing after second‐line therapy have a dismal prognosis and novel approaches are required for this patient group. Based on promising (pre‐)clinical data and the favourable toxicity profile, we performed a phase II clinical trial with the JAK inhibitor ruxolitinib in patients with relapsed or refractory cHL (r/r cHL).MethodsPatients ≥18 years with histologically confirmed r/r cHL who failed second‐line treatment were included. Ruxolitinib was given orally at a dose of 25 mg twice daily in continuous 28‐day cycles until progression or unacceptable toxicity. Primary endpoint was the PET/CT‐based overall response rate (ORR; complete response (CR) or partial response (PR)) after 2 cycles; secondary endpoints included progression‐free (PFS) and overall survival (OS) as well as feasibility. The Jericho Trial adopted a 2‐stage phase 2 design (Simon 1989).ResultsAmong the 12 included patients in stage 1, 2 had a PR, 3 had a stable disease (SD) and 6 had progressive disease (PD) after two treatment cycles (ORR: 2/12 evaluable patients, 16.7%). Median PFS was 3.6 months, the 1‐year OS estimate was 50.6% (median not reached). The toxicity profile was favourable with only one grade IV adverse event (7.1%) reported.ConclusionRuxolitinib exhibited a favourable side effect profile but modest activity in r/r cHL. Although the formal stopping criterion after stage 1 was not met, the trial did not continue to stage 2 due to the low response and PFS rates observed in stage 1.
Clinical autonomic nervous system laboratories in Europe
Authors: Habek Mario , Leys Fabian , Krbot Skorić Magdalena , Reis Carneiro Diogo , Calandra‐Buonaura Giovanna , Camaradou Jennifer , Chiaro Giacomo , Cortelli Pietro , Falup‐Pecurariu Cristian , Granata Roberta , Guaraldi Pietro , Helbok Raimund , Hilz Max J. , Iodice Valeria , Jordan Jens , Kaal Evert C. A. , Kamondi Anita , Pavy Le Traon Anne , Rocha Isabel , Sellner Johann , Senard Jean Michel , Terkelsen Astrid , Wenning Gregor K. , Berger Thomas , Thijs Roland D. , Struhal Walter , Fanciulli Alessandra ,   the Collaborators of the European Network of Clinical ANS laboratories
Published: September 2022

AbstractBackground and purposeDisorders of the autonomic nervous system (ANS) are common conditions, but it is unclear whether access to ANS healthcare provision is homogeneous across European countries. The aim of this study was to identify neurology‐driven or interdisciplinary clinical ANS laboratories in Europe, describe their characteristics and explore regional differences.MethodsWe contacted the European national ANS and neurological societies, as well as members of our professional network, to identify clinical ANS laboratories in each country and invite them to answer a web‐based survey.ResultsWe identified 84 laboratories in 22 countries and 46 (55%) answered the survey. All laboratories perform cardiovascular autonomic function tests, and 83% also perform sweat tests. Testing for catecholamines and autoantibodies are performed in 63% and 56% of laboratories, and epidermal nerve fiber density analysis in 63%. Each laboratory is staffed by a median of two consultants, one resident, one technician and one nurse. The median (interquartile range [IQR]) number of head‐up tilt tests/laboratory/year is 105 (49–251). Reflex syncope and neurogenic orthostatic hypotension are the most frequently diagnosed cardiovascular ANS disorders. Thirty‐five centers (76%) have an ANS outpatient clinic, with a median (IQR) of 200 (100–360) outpatient visits/year; 42 centers (91%) also offer inpatient care (median 20 [IQR 4–110] inpatient stays/year). Forty‐one laboratories (89%) are involved in research activities. We observed a significant difference in the geographical distribution of ANS services among European regions: 11 out of 12 countries from North/West Europe have at least one ANS laboratory versus 11 out of 21 from South/East/Greater Europe (p = 0.021).ConclusionsThis survey highlights disparities in the availability of healthcare services for people with ANS disorders across European countries, stressing the need for improved access to specialized care in South, East and Greater Europe.
Subtle vascular and astrocytic changes in the brain of coronavirus disease 2019 (COVID‐19) patients
Authors: Rosu Gabriela Camelia , Mateescu Valentin Octavian , Simionescu Alexandra , Istrate‐Ofiteru Anca‐Maria , Curcă George Cristian , Pirici Ionica , Mogoanta Laurentiu , Mindrila Ion , Kumar‐Singh Samir , Hostiuc Sorin , Pirici Daniel 
Published: September 2022

AbstractBackground and purposeIn the central nervous system, a multitude of changes have been described associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, such as microglial activation, perivascular lymphocyte cuffing, hypoxic‐ischaemic changes, microthrombosis, infarcts or haemorrhages. It was sought here to assess the vascular basement membranes (vBMs) and surrounding perivascular astrocytes for any morphological changes in acute respiratory syndrome (coronavirus disease 2019, COVID‐19) patients.MethodsThe light microscopy morphology of the vBMs and perivascular astrocytes from brains of 14 patients with confirmed SARS‐CoV‐2 infection was analysed and compared to four control patients utilizing fluorescent immunohistochemistry for collagen IV and astrocytes (GFAP), endothelia (CD31), tight junction 1 (TJ1) adhesion protein, as well as the aquaporin 4 (AQP4) water channel. On 2D and 3D deconvoluted images from the cortex and white matter, vessel densities, diameters, degree of gliosis, collagen IV/GFAP and GFAP/AQP4 colocalizations were calculated, as well as the fractal dimension of astrocytes and vBMs viewed in tangential planes.ResultsFractal dimension analysis of the GFAP‐stained astrocytes revealed lower branching complexities and decreased GFAP/collagen IV colocalization for COVID‐19 patients. Interestingly, vBMs showed significantly increased irregularities (fractal dimension values) compared to controls. Vessel diameters were increased in COVID‐19 cases, especially for the white matter, TJ1 protein decreased its colocalization with the endothelia, and AQP4 reduced its co‐expression in astrocytes.ConclusionsOur data on the irregularity of the basement membranes, loss of endothelial tight junction, reduction of the astrocyte end‐feet and decrease of AQP4 suggest subtle morphological changes of the blood–brain barrier in COVID‐19 brains that could be linked with indirect inflammatory signalling or hypoxia/hypercapnia.