bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-desmoglein2 autoantibodies are present in patients with cardiac sarcoidosis and correlate with cardiac inflammation
Authors: Suna G , Kolios A , Chatterjee D , Fatah M , Gasperetti A , Casella M , Sommariva E , Franzen D , Manka R , Pazhenkottil A , Ruschitzka F , Boyman O , Duru F , Hamilton RM , Saguner AM 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): The Zurich ACM Program is supported by generous grants from the Georg and Bertha Schwyzer-Winniker Foundation, the Baugarten Foundation, Swiss National Science Foundation, Swiss Heart Foundation and Wild Foundation. This work is also supported by a Canadian Institutes of Health Research grant (FRN: 162402) and the Labatt Heart Centre and Waugh Family Innovation Funds, Caitlin Elizabeth Morris Memorial Fund, Alex Corrance Memorial Foundation and Meredith Cartwright.
BACKGROUND Arrhythmogenic right ventricular cardiomyopathy (ARVC) has several phenocopies such as cardiac sarcoidosis (CS), idiopathic outflow tract ventricular tachycardia (OT-VT) and myocarditis. Differentiation between these entities can be challenging. Recently, we have identified diagnostic anti-desmoglein-2 autoantibodies (anti-DSG2 Abs) in patients with ARVC.
PURPOSE We sought to examine whether anti-DSG2 Abs are also present in clinical phenocopies of ARVC.
METHODS Anti-DSG2 Abs in sera of 25, 19 and 22 patients with sarcoidosis, OT-VT and myocarditis, respectively, were assessed by western blots and ELISA. Clinical and imaging parameters, as well as conventional biomarkers were correlated to detected anti-DSG2 Ab intensity levels.
RESULTS Anti-DSG2 Abs, at various intensities, were identified in 6/25 (24%) patients with sarcoidosis, all presenting with CS, but were absent in patients with OT-VT and myocarditis. Cardiac 18F- fluorodeoxyglucose positron emission tomography (18F-FDG PET) was positive in all sarcoidosis patients with positive anti-DSG2 Abs, corresponding to a median PET maximum standardized uptake value (SUVmax) of 5.65 [IQR: 5.15 – 10.9]. In sarcoidosis patients without anti-DSG2 Abs, the SUVmax values were significantly lower with a median of 0 [IQR: 0 – 4] (p = 0.011). The Pearson correlation coefficient (R) was 0.188 (p = 0.039) indicating a positive correlation between cardiac 18F-FDG uptake and anti-DSG2 Abs. No significant correlation was detected for any of the other clinical parameters and biomarkers.
CONCLUSIONS In addition to being present in ARVC, anti-DSG2 Abs are also found in CS, a common phenocopy of ARVC; conversely, anti-DSG2 Abs are absent in idiopathic OT-VT and myocarditis. Anti-DSG2 Ab levels positively correlate with myocardial disease activity in CS as indicated by cardiac 18F-FDG PET scanning. Abstract Figure. Central illustration
Human-specific desmoglein 2 mutations in mice models of arrythmogenic right ventricular cardiomyopathy reproduce patients" phenotype
Authors: Zankov D , Ohno S 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease that inevitably leads to terminal heart failure and sudden cardiac death due to ventricular arrhythmias. Excessive exercise accelerates the progress of the disease. At present, there is no curative therapy for ARVC. The disease is mostly caused by mutations in genes encoding desmosomal proteins, and Japanese ARVC patients commonly possess missense mutations in DSG2. Although there are animal models with Dsg2-related cardiomyopathy, they do not reﬂect the precise human disease caused by missense mutations in DSG2.

Purpose
We aimed to generate knock-in mouse models of ARVC carrying Dsg2 mutations equivalent to those found in ARVC patients.

Methods
We introduced Dsg2 mutations (R297C, D499A), which were equivalent to most common mutations in Japanese ARVC patients, to mice by CRSPR/Cas9 genome editing system. Echocardiography and treadmill training were performed to evaluate the cardiac phenotype of the mouse models.

Results
There is phenotype inequality between the two lines of Dsg2 knock-in mice. In R297C mice, all the homozygotes died suddenly until the age of 20 weeks, and half of the heterozygotes until the age of 25 weeks. Heart examination of the deceased homozygous mice demonstrated enlarged cavities, predominantly in the right ventricles, and scattered pale patches suggesting ﬁbrotic replacement of the myocardium. Echocardiography of four 9-week-old homozygous mice shows acoustically dense zones (white arrows in the left ﬁgure) and left ventricular dysfunction (ejection fraction (EF) &lt; 35%). Exploration of the hearts of sacriﬁced mice conﬁrmed echocardiographical ﬁndings (red arrow in the right ﬁgure) demonstrating scattered pale regions similar to those in suddenly died mice. In contrast, homozygous and heterozygous D499A mice survived without sudden death. Both mutant mice develop heart failure after the age of 30 weeks. To mimic the effect of exercise, we performed treadmill training for two months started from 11 weeks old in both types of D499A and heterozygous R297C mice. The training signiﬁcantly accelerated cardiac dysfunction: all D499A mice (homo and hetero) and half of heterozygous R297C developed biventricular dysfunction at the age of 19 weeks though no change in WT. EF for R297C heterozygous mice, D499A heterozygous and D499A homozygous mice decreased from 64.4 ± 4.3%, 71.9 ± 1.7% and 73.9 ± 1.1 to 31.2 ± 5.7%, 16.6 ± 2.1% and 12.4%±1.9, respectively. Treadmill training did not alter significantly EF in WT mice: 71.8 ± 2.3% before and 67.5 ± 1.4 at the end of physical challenge.

Conclusion
We generated mouse model of ARVC mutations that mimic the exact gene defect found in the humans. Our experimental work conﬁrms signiﬁcant overlap to the human phenotype. Further investigation will clarify the underlying cellular mechanisms. Abstract Figure. A heart from homozygous R297C mouse
Functional characterization of drug responses in induced pluripotent stem cell-derived cardiomyocytes from a short QT syndrome type 5 patient
Authors: Lee J , Hohn A , Emmenegger V , Ulusan H , Akin I , Saguner AM , Zhou X , Duru F , Hierlemann A , El-Battrawy I 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: Other. Main funding source(s): ETH Zurich Personalized Health and Related Technologies; German Centre for Cardiovascular Research

Introduction
Short QT syndrome (SQTS) and Brugada syndrome (BrS) are rare channelopathies causing sudden cardiac death (SCD). There are only few investigations of effective therapies of SQTS and BrS linked to CACNB2 variants. Since treatment data of SQTS are sparse, we studied drug responses of induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) 2D cultures carrying a mutation in the CACNB2 gene from a SQTS type 5 (SQT5) patient with an established phenotype. We used high-density microelectrode arrays (HD-MEAs), patch clamp, and calcium-transient imaging.

Purpose
To investigate the electrophysiological responses of SQT5 patient-derived iPSC-CMs upon exposure to antiarrhythmic drugs.

Methods
Human iPSCs, derived from a SQT5 patient and a healthy donor, were cultured and differentiated into cardiomyocytes by temporal modulation of the Wnt signaling. For electrophysiological measurements, spontaneously beating cardiomyocytes at day 40-60 were dissociated and plated a) on petri dishes for patch clamp and calcium-transient measurements and b) directly on HD-MEAs. Antiarrhythmic drugs, including sotalol, quinidine, and flecainide, were dosed to the cells after plating as soon as stable activity levels were measured. After baseline measurements, drug doses were sequentially increased from low to high concentrations.

Results
We observed spontaneous and synchronous beating of SQT5 patient- and healthy donor-derived iPSC-CMs. Quinidine, which is known to be effective for treatment of SQTS with possible differences for subtypes, prolonged field-potential duration (FPD) and action-potential duration in SQT5 patient-derived iPSC-CMs. Sotalol slightly increased FPD at 30µM as measured with HD-MEAs, whereas action-potential duration (APD) measured through patch clamp did not exhibit a notable effect at 30 µM. APD became shorter at higher concentrations, which is in line with clinical data of SQTS patients. HD-MEA measurements showed that flecainide shortened the FPD of SQT5 patient-derived CMs at 20µM. For healthy donor-derived iPSC-CMs, quinidine, sotalol, and flecainide prolonged FPDs in HD-MEA measurements. Using calcium-transient imaging, quinidine showed a slight antiarrhythmic effect, whereas sotalol did not have antiarrhythmic effects.

Conclusion
We used HD-MEAs, patch clamp, and calcium-transient imaging to analyze electrophysiological responses of SQT5 patient-derived iPSC-CMs upon dosage of antiarrhythmic drugs. Our preliminary results show that quinidine - but not flecainide - could prolong the repolarization duration in SQT5 patient-derived iPSC-CMs.
Repolarization characteristics indicate electrical instability in ventricular arrhythmia originating from papillary muscle
Authors: Muenkler P , Klatt N , Scherschel K , Kuklik P , Jungen C , Cavus E , Eickholt C , Christoph J , Christ T , Willems S , Riedel R , Kirchhof P , Meyer C 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): DZHK (German Center for Cardiovascular Research)

Introduction
Cardiac arrhythmia originating from the papillary muscle can trigger ventricular fibrillation and cause sudden cardiac death even in the absence of structural heart disease. Yet, no clinical parameters are known to reflect the propensity of arrhythmia to degenerate into ventricular fibrillation.

Purpose
We aimed at identification of parameters associated with degeneration of ventricular arrhythmia into ventricular fibrillation.

Methods
Ventricular arrhythmia was induced by aconitine injection into the papillary muscle of healthy sheep (n = 12) in an open-chest model. Endocardial high-density-mapping and epicardial mapping were performed. We determined repolarization time and activation-recovery-interval according to the Wyatt method.

Results
During focal arrhythmia faster conduction occurred in longitudinal and basal direction than transversal and apical direction. The electrical restitution curve, modelling relation of diastolic interval and activation-recovery-interval, is steeper in aconitine-induced ventricular arrhythmia than in ventricular pacing or sinus rhythm. Steeper restitution curves reflect electrical instability and propensity to degenerate into ventricular fibrillation. The repolarization-related parameters activation-recovery interval and repolarization time exhibit higher heterogeneity per beat in ventricular arrhythmia preceding degeneration into ventricular fibrillation. Repolarization time in relation to cycle length (RT/CL), which can easily be measured during electrophysiological procedures, differentiates self-limiting from degenerating arrhythmia with high specificity and sensitivity.

Conclusion
In structurally normal ovine hearts, the ratio of repolarization and cycle length (RT/CL) in ventricular arrhythmia and greater dispersion of repolarization are indicators of subsequent degeneration into ventricular fibrillation. While dispersion of repolarization is not easily acquired in clinical routine, a simple index (RT/CL) may be sufficient to differentiate between self-limiting and electrically instable arrhythmia with propensity to degenerate to ventricular fibrillation. Abstract Figure. Repolarization in VA model
Facilitators and barriers to implementing lifestyle intervention programme to prevent cognitive decline
Authors: Kulmala Jenni , Rosenberg Anna , Ngandu Tiia , Hemiö Katri , Tenkula Tarja , Hyytiä Arja , Vienola Minna , Huhtamäki-Kuoppala Minna , Saarinen Anneli , Korkki Saana , Laatikainen Tiina , Solomon Alina , Kivipelto Miia 
Published: May 2021

Abstract

Background
The Finnish Intervention Study to Prevent Cognitive Impairment and Disability is a randomized controlled trial that has tested the efficacy of a multidomain intervention targeting modifiable risk factors to prevent cognitive impairment/dementia. A combination of healthy diet, physical, social and cognitive activity, and management of cardiovascular risks was shown to be an effective model to promote brain health among older people. The aim of this qualitative study was to explore healthcare professionals’ perceptions of facilitators and barriers to implementing this lifestyle programme into health care.

Methods
Four semi-structured focus group interviews were conducted among healthcare professionals working in primary care and in non-governmental organizations (N=27). Participants were asked to discuss their perceptions of facilitators and barriers for implementing the multidomain intervention into clinical practice. Interviews were analyzed using content analysis.

Results
Barriers and facilitators described by the healthcare professionals were related to infrastructure and resources, client’s personal characteristics and the lifestyle intervention itself. These main categories included several sub-categories related to knowledge, motivation, resources, individualization and collaboration. The interviewees pointed out that more education on dementia prevention is needed, the work should be coordinated efficiently, resources to provide preventive health care should be adequate and multiprofessional collaboration is needed.

Conclusions
Transferring a lifestyle intervention from a trial-setting to real life requires knowledge about the factors that influence effective implementation. Identifying drivers and constraints of successful implementation helps to design and tailor future prevention programmes, increases motivation and adherence and supports system change.
Insights into Old English Lexicography: Lemmatisation ofgĀnand Its Prefix-Formations using a Corpus-Based Database
Authors: García Fernández Laura 
Published: May 2021

AbstractThis article contributes to Old English lexicography by providing a list of lemmas and inflectional forms for the Old English derived verbs (prefixed verbs) of gān ‘to go’. Entries for these lemmas, if listed by Old English dictionaries, are often incomplete, but, more importantly, they are not based on a lemmatised corpus. This is particularly problematic in the case of languages like Old English that are rife with morphological variation. The methodology followed in this study comprises searches on a lexical database and manual revision of the hits. The searches are launched on the lemmatiser Norna, and the hits are checked with available lexicographical sources, secondary sources and annotated corpora. Finally, ambiguous cases are examined in their context. The final list of lemmas and inflectional forms amounts to 104 inflectional forms which are attributed to 14 different lemmas, including one lemma and up to 61 inflectional forms never before listed by dictionaries. Special attention is paid to the contrast between what is attested in the Old English corpora and what is available from the sources. In addition to providing insights into the inventory of lemmas and inflectional forms for the derivatives (prefixed verbs) of the verb gān as attested in The Dictionary of Old English Corpus, which was not available until now from lexicographical sources, this article contributes recommendations for the linguistic analysis of Old English using corpus-based lexical databases.
Beyond timelines: the challenges of combining theoretical premises and speakers’ insights about the assessment, validation and inclusion of Spanish neologisms in dictionaries
Authors: Sánchez Ibáñez Miguel , Maroto Nava 
Published: May 2021

Abstract
Lexicographic exclusion filtering as a strategy to determine the suitability of neologisms to be included in dictionaries has proved to be insufficient. Therefore, a methodology to rank neologisms in a more objective and quantitative way, based on their most distinctive features as new words is put forward here. In addition, the results of applying this methodology to a sample of more than 3,000 units compiled from Spanish newspapers over a specific time span (2009-2016) are contrasted along with the insights provided by a group of native speakers collected by means of a crowdsourcing strategy. By combining theoretical approaches and speakers’ insights, the validity of the suggested methodology is partially corroborated. Moreover, insights given by the speakers involved concerning their prescriptive conception of neology and its place within dictionaries are outlined.
Smaller decline of renal function after nephroureterectomy predicts poorer prognosis of upper tract urothelial carcinoma: a multicentre retrospective study
Authors: Yamada Yukio , Nakagawa Tohru , Miyakawa Jimpei , Kawai Taketo , Tabata Mariko , Kaneko Tomoyuki , Taguchi Satoru , Naito Akihiro , Hikatsu Masahiro , Sato Yusuke , Murata Taro , Matsumoto Akihiko , Miyazaki Hideyo , Suzuki Motofumi , Enomoto Yutaka , Nishimatsu Hiroaki , Kondo Yasushi , Takeuchi Takumi , Tanaka Yoshinori , Kume Haruki 
Published: May 2021

Abstract

Purpose
Renal function is frequently impaired in the patients with upper tract urothelial carcinoma. We aimed to evaluate the impact of renal function and its change after surgery on survival rates in patients with upper tract urothelial carcinoma after nephroureterectomy.

Methods
The study cohort comprised 755 patients with upper tract urothelial carcinoma who underwent nephroureterectomy between 1995 and 2016 at nine hospitals in Japan. Estimated glomerular filtration rate was calculated using the three-variable Japanese equation for glomerular filtration rate estimation from serum creatinine level and age. Outcomes were recurrence-free, cancer-specific and overall survivals. Univariate and multivariate Cox proportional hazards regression analyses were used.

Results
Median patients’ age was 72 years old. Pre- and post-surgical median estimated glomerular filtration rate were 55.5 and 42.9 ml/min/1.73 m2, respectively. Median estimated glomerular filtration rate decline after surgery, which represents function of the affected side kidney, was 13.1 ml/min/1.73 m2. The 5-year recurrence-free, cancer-specific and overall survivals were 68.3, 79.4 and 74.0%, respectively. Multivariate analysis indicated that lower preoperative estimated glomerular filtration rate and estimated glomerular filtration rate decline were associated with poorer recurrence-free, cancer-specific and overall survivals, but post-operative estimated glomerular filtration rate was not. Estimated glomerular filtration rate decline was more significant poor-prognosticator than preoperative estimated glomerular filtration rate. Proportions of the patients with estimated glomerular filtration rate &lt;60 ml/min/1.73 m2 before surgery were 50.6 and 73.2% in organ-confined disease and locally advanced disease, respectively (P &lt; 0.0001). After surgery, they were 91.6 and 89.8%, respectively (P = 0.3896).

Conclusions
Lower preoperative renal function, especially of the affected side kidney, was significantly associated with poor prognosis after nephroureterectomy for upper tract urothelial carcinoma. Many patients with locally advanced disease have reduced renal function at diagnosis and even more after surgery.
Volatility Bursts: A Discrete-Time Option Model with Multiple Volatility Components
Authors: Lilla Francesca 
Published: May 2021

Abstract
I propose an affine discrete-time model, called Vector Autoregressive Gamma with volatility Bursts (VARG-B) in which volatility experiences, in addition to frequent and small changes, periods of sudden and extreme movements generated by a latent factor which evolves according to the Autoregressive Gamma Zero process. A key advantage of the discrete-time specification is the possibility of estimating the model using Kalman Filter techniques. Moreover, the VARG-B model leads to a fully analytic conditional Laplace transform which boils down to a closed-form option pricing formula. When estimated on S&P500 index options and returns, the new model provides more accurate option pricing and modeling of the IV surface compared with some alternative models.
Long-Term Itching in a Tourist Following Bite by a Nymph of Dermacentor auratus (Acari: Ixodidae) in Cambodia
Authors: Chitimia-Dobler Lidia , Schaper Sabine , Bröker Michael , Nava Santiago 
Published: May 2021

Abstract
The impact of tick bites during holidays in tropical countries is seldom reported. Here, we describe long-term skin alterations and itching experienced by a German tourist following the bite of a nymph of Dermacentor auratus Supino, 1897 in Cambodia. Tick infestation may be neglected by travelers. Therefore, careful travel history is necessary when travelers report a tick bite after spending holiday in tropical and subtropical countries.
Impact of pharmacist intervention on antidepressant medication adherence and disease severity in patients with major depressive disorder in fragile north-east Nigeria
Authors: Yusuf Hadiza , Magaji Mohammed G , Maiha Bilkisu B , Yakubu Sani I , Haruna Wazis C , Mohammed Shafiu 
Published: May 2021

AbstractObjectivesMedication adherence is emerging as a major public health challenge particularly in patients with depression. The aim of this study was to explore the usefulness of a pharmacist intervention to improve antidepressant medication adherence and disease severity in patients with major depressive disorder.MethodsThis prospective interventional study was conducted between April 2019 and March 2020 among 101 patients at the Federal Neuro-Psychiatric Hospital, Maiduguri, Nigeria. Consenting patients were randomised into usual care or intervention groups using a computer-generated list. Data were collected at baseline, 3 months and 6 months. Medication adherence and depression severity were assessed using the Medication Adherence Rating Scale and Beck Depression Inventory respectively.Key findingsAt baseline, both the usual care and intervention groups had low mean scores for medication adherence [5.22 (SD = 1.51) versus 5.46 (SD = 1.46)] and high mean scores for depression severity [24.16 (SD = 13.50) versus 27.07 (SD = 16.12)]. At 6 months, there was a significant difference (P &lt; 0.001) between the mean medication adherence scores of 5.22 (SD = 1.90) and 9.15 (SD = 1.62), in the usual care and intervention groups respectively. A significant difference (P = 0.033) was also observed at 6 months between the mean depression severity scores of the usual care and intervention groups [21.40 (SD = 11.52) and 17.34 (SD = 6.96)]. Medication adherence (P &lt; 0.001, Partial eta squared = 0.279) and depression severity (P &lt; 0.001, Partial eta squared = 0.170) positively changed with time in the presence of the intervention.ConclusionsThe intervention significantly improved antidepressant medication adherence and disease severity in patients with major depressive disorder.
Lemierre’s Syndrome Due to the Zoonotic Anaerobe Bacteroides pyogenes: Case Report and Literature Review
Authors: Goggin Kathryn P , Beckmann Nicholas , Bettin Kristen , Carrillo-Marquez Maria , Wood Joshua , Arnold Sandra R 
Published: May 2021

Abstract
Although Fusobacterium necrophorum is well described as an emerging pathogen of acute mastoiditis in young children, infection with other anaerobes can lead to similar severe sequelae including intracranial and extracranial suppurative thrombophlebitis and sepsis. We describe a patient whose unremarkable exposure history assumed increased significance upon obtaining the results of 16S next generation sequencing from a surgical specimen. The novel pathogen Bacteroides pyogenes is reviewed herein.