bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arrhythmogenic Right Ventricular Cardiomyopathy-Associated Desmosomal Variants Are Rarely De Novo
Authors: van Lint Freyja H.M. , Murray Brittney , Tichnell Crystal , Zwart Rob , Amat Nuria , Lekanne Deprez Ronald H. , Dittmann Sven , Stallmeyer Birgit , Calkins Hugh , van der Smagt Jasper J. , van den Wijngaard Arthur , Dooijes Dennis , van der Zwaag Paul A. , Schulze-Bahr Eric , Judge Daniel P. , Jongbloed Jan D.H. , van Tintelen J. Peter , James Cynthia A. 
Published: August 2019

Background:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with pathogenic/likely pathogenic (P/LP) variants in genes encoding the cardiac desmosomal proteins. Origin of these variants, including de novo mutation rate and extent of founder versus recurrent variants has implications for variant adjudication and clinical care, yet this has never been systematically investigated.

Methods:

We identified arrhythmogenic right ventricular cardiomyopathy probands who met 2010 Task Force Criteria and had undergone genotyping that included sequencing of the desmosomal genes (
PKP2
,
DSP
,
DSG2
,
DSC2
, and
JUP
) from 3 arrhythmogenic right ventricular cardiomyopathy registries in America and Europe. We classified the desmosomal variants, defined the contribution of unique versus nonunique (ie, not family-specific) P/LP variants, and identified the frequency and characteristics of de novo variants. Next, we haplotyped nonunique variants to determine how often they likely represent a single mutation event in a common ancestor (implied by shared haplotypes) versus multiple mutation events at the same genetic location.

Results:

Of 501 arrhythmogenic right ventricular cardiomyopathy probands, 322 (64.3%) carried 327 desmosomal P/LP variants. Most variants (n=247, 75.6%, in 245 patients) were identified in more than one proband and, therefore, considered nonunique. For 212/327 variants (64.8%) genetic cascade screening was performed extensively enough to identify the parental origin of the P/LP variant. Only 3 variants were de novo, 2 of which were whole gene deletions. For 24 nonunique P/LP
PKP2
variants, haplotyping was conducted in 183 available families. For all 24 variants, multiple seemingly unrelated families sharing identical haplotypes were identified, suggesting that these variants originate from common founders.

Conclusions:
Most desmosomal P/LP variants are inherited, nonunique, and originate from ancient founders. Two of 3 de novo variants were large deletions. These observations inform genetic testing, cascade screening, and variant adjudication.
Coupling to Gq Signaling Is Required for Cardioprotection by an Alpha-1A-Adrenergic Receptor Agonist
Authors: Myagmar Bat-Erdene , Ismaili Taylor , Swigart Philip M. , Raghunathan Anaha , Baker Anthony J. , Sahdeo Sunil , Blevitt Jonathan M. , Milla Marcos E. , Simpson Paul C. 
Published: August 2019

Rationale:
Gq signaling in cardiac myocytes is classically considered toxic. Targeting Gq directly to test this is problematic, because cardiac myocytes have many Gq-coupled receptors.

Objective:
Test whether Gq coupling is required for the cardioprotective effects of an alpha-1A-AR (adrenergic receptor) agonist.

Methods and Results:
In recombinant cells, a mouse alpha-1A-AR with a 6-residue substitution in the third intracellular loop does not couple to Gq signaling. Here we studied a knockin mouse with this alpha-1A-AR mutation. Heart alpha-1A receptor levels and antagonist affinity in the knockin were identical to wild-type. In wild-type cardiac myocytes, the selective alpha-1A agonist A61603-stimulated phosphoinositide-phospholipase C and myocyte contraction. In myocytes with the alpha-1A knockin, both A61603 effects were absent, indicating that Gq coupling was absent. Surprisingly, A61603 activation of cardioprotective ERK (extracellular signal-regulated kinase) was markedly impaired in the KI mutant myocytes, and A61603 did not protect mutant myocytes from doxorubicin toxicity in vitro. Similarly, mice with the α1A KI mutation had increased mortality after transverse aortic constriction, and A61603 did not rescue cardiac function in mice with the Gq coupling-defective alpha-1A receptor.

Conclusions:
Gq coupling is required for cardioprotection by an alpha-1A-AR agonist. Gq signaling can be adaptive.
Assessment of the Most Optimal Control Tissue for Intracranial Aneurysm Gene Expression Studies
Authors: Laarman Melanie D. , Kleinloog Rachel , Bakker Mark K. , Rinkel Gabriël J.E. , Bakkers Jeroen , Ruigrok Ynte M. 
Published: August 2019

Background and Purpose—
Finding adequate control tissue for intracranial aneurysm (IA) pathophysiological studies, including gene expression studies, can be challenging. We compared gene expression profiles of superficial temporal, cortical, and circle of Willis (CoW) arteries and IA in search of the most optimal control tissue for future experiments.

Methods—

We compared RNA-sequencing data of IA samples and of superficial temporal, cortical, and CoW artery samples using Pearson correlation, Euclidean distance, and principal component analysis. We used the Mann-Whitney
U
test for comparison of Pearson correlation coefficients and Euclidean distances, to assess which control tissue is most similar to IA in terms of gene expression. Other unrelated tissues were used as negative controls.

Results—

The cortical and the CoW arteries were more similar to IA in terms of gene expression than the superficial temporal artery. This was based on Pearson correlation (+0.023 [90% CI, 0.017/0.029;
P
=1.9E-09] for the cortical artery and +0.034 [90% CI, 0.028/0.040;
P
=6.0E-15] for the CoW artery compared with the superficial temporal artery), Euclidean distance (−25.71 [90% CI, −31.54/−20.02;
P
=1.9E-11] for the cortical artery and −38.09 [90% CI, −44.08/−32.19;
P
<2.2E-16] for the CoW artery compared with the superficial temporal artery) and principal component analysis. In all analyses, the unrelated tissues formed separate groups compared with IA and the 3 control arteries.

Conclusions—
The cortical arteries and the CoW arteries are better controls for gene expression studies on IA than the superficial temporal artery. This probably relates to differences in anatomy of these tissues, such as the presence of an external elastic lamina in the extracranial vasculature and absence in the intracranial vasculature, because IAs, cortical arteries, and CoW arteries are all intracranial while the superficial temporal artery is extracranial. Since CoW arteries can only be obtained postmortem, cortical arteries are preferred over CoW arteries.
Effect of microscopically assisted decompression with micro-hook scalpel in the surgical treatment of ossification of the posterior longitudinal ligament
Authors: Yang Sheng , Lu Jianmin , Fu Dapeng , Shang Depeng , Zhou Fei , Liu Jifeng , Cao Meng 
Published: August 2019

Objective This study was performed to investigate the effect of microscopically assisted decompression using a micro-hook scalpel on ossification of the posterior longitudinal ligament (OPLL). Methods Sixty-one patients with OPLL were divided into Group A (posterior surgery with laminectomy of the responsible segment and lateral mass screw fixation) and Group B (anterior cervical corpectomy with intervertebral titanium cage fusion). Neurological function was assessed by the Japanese Orthopaedic Association (JOA) score, visual analog scale (VAS) score, and recovery rate. The fixation status and the result of spinal canal decompression were radiographically assessed. Results In Groups A and B, the JOA score was significantly higher and the VAS score was significantly lower at 1 week postoperatively and at the final follow-up than during the preoperative period. The mean recovery rate in Group A and B was 59.92% ± 13.46% and 62.28% ± 14.00%, respectively. Postoperative radiographs showed good positioning and no damage to the internal fixation materials. The spinal canal was also fully decompressed. Conclusions Microscopically assisted decompression with a micro-hook scalpel in both anterior and posterior surgeries achieved good clinical effects in patients with OPLL.
A nomogram for predicting the risk of sepsis in patients with acute cholangitis
Authors: Liu Qingqing , Zhou Quan , Song Meina , Zhao Fanfan , Yang Jin , Feng Xiaojie , Wang Xue , Li Yuanjie , Lyu Jun 
Published: August 2019

Objective Sepsis is a serious complication of acute cholangitis. We aimed to establish a nomogram for predicting the probability of sepsis in patients with acute cholangitis. Methods Subjects were patients with acute cholangitis in the Medical Information Mart for Intensive Care database. Extraneous variables were excluded based on stepwise regression. The nomogram was established using logistic regression. Results The predictive model comprised five variables: age (odds ratio [OR]: 1.03, 95% confidence interval [CI]: 1.01–1.04), ventilator-support time (OR: 1.004, 95% CI: 1.001–1.008), diabetes (OR: 10.74, 95% CI: 2.80–70.57), coagulopathy (OR: 2.92, 95% CI: 1.83–4.73) and systolic blood pressure (OR: 0.62, 95% CI: 0.41–0.93). The areas under the receiver operating characteristic curve of the nomogram for the training and validation sets were 0.700 and 0.647, respectively. The Hosmer–Lemeshow goodness-of-fit test revealed high concordance between the predicted and observed probabilities for both the training and validation sets. The calibration plot also demonstrated good agreement between the predicted and observed outcomes for both the training and validation sets. Conclusions We developed and validated a risk-prediction model for sepsis in patients with acute cholangitis. Our results will be helpful for preventing sepsis in patients with acute cholangitis.
Comparison of short and long axis ultrasound-guided approaches to internal jugular vein puncture: a meta-analysis
Authors: Zhang Jian , Wang Xiaohan , Miao Shuai , Shi Mengzhu , Wang Guanglei , Tu Qing 
Published: August 2019

Objective To compare short-axis versus long-axis plane for ultrasound-guided internal jugular vein puncture. Methods PubMed, Embase, Cochrane Library and CNKI databases were searched for randomized controlled trials, published to 1 June 2019, that compared short- versus long-axis plane in ultrasound-guided internal jugular vein puncture. Statistical analyses were performed using RevMan software, version 5.3. Statistical results are presented as risk ratio (RR) (95% confidence interval [CI]) for dichotomous data and standard mean difference (SMD) (95% CI) for continuous data. Results Ten studies fulfilled the inclusion criteria. Analyses of pooled results showed no statistically significant differences in arterial puncture incidence between the two planes (RR 0.73 [95% CI 0.38, 1.39]). First-pass success rate (RR 1.08 [95% CI 0.95, 1.22]), total success rate (RR 1.00 [95% CI 0.99, 1.02]) and number of attempts required (SMD –0.09 [95% CI –0.37, 0.18]) were also similar between the two approaches. Trial sequential analysis indicated that the available evidence was insufficient to detect potential differences between the two techniques. Conclusions There is insufficient data for an evidence-based choice of either short- or long-axis plane in ultrasound-guided internal jugular vein puncture.
Maternal wellbeing and pregnancy outcomes in anaesthetic trainees
Authors: Zacher Rosmarin 
Published: August 2019

The importance of supporting and maintaining doctors’ health and wellbeing cannot be overstated. Combined with the undisputed status of work in medicine as both strenuous and stressful, pregnancy is a unique time during which the mother and unborn baby may be at risk of adverse outcomes. A narrative literature review is presented with a focus on studies of relevance to pregnancy in anaesthesia trainees, however much of the evidence is drawn from studies involving anaesthetic consultants, trainees in other specialties and pregnant workers in general. After a brief exploration into historical concepts in occupational hazards and adverse pregnancy outcomes, further discussion ensues on more recent evidence in relation to specialist training (or ‘residency’), the impact of work stressors and maternal psychological state on pregnancy outcomes and attitudes towards pregnancy during specialist training. Finally, occupational guidelines are considered along with the rationale for ‘pregnancy-friendly’ workplaces and suggestions for future research in this area for both the profession and employers.
‘Reverse-Engineering’ of a Results Framework for Monitoring and Evaluation – The Case of Punjab Vocational Training Council
Authors: Bashir Mohsin 
Published: August 2019

Several government and non-profit organizations in Pakistan are currently going through a transition towards performance management systems that are based on internationally accepted monitoring and evaluation (M&E) frameworks. More often than not, these transitions are driven by requirements of donor organizations. While it is fairly uncomplicated and helpful to develop an M&E framework before the initiation of a programme, organizations find it quite tricky to develop such a system while the operations are already underway. This case presents the story of a public sector organization that created an M&E team that was able to successfully reverse-engineer its operations into an M&E framework. It can, therefore, prove to be a very helpful resource for managers and consultants attempting to develop M&E frameworks for ongoing programmes. Findings and analysis are presented in such a way that the case bears the appearance of a step-by-step guideline. While the case is focussed around developing a results framework, the learning can easily be generalized to other platforms, specifically the logical framework approach. Data for this case was collected during a 6-month-long consulting assignment. Data sources include interviews with the employees, internal organizational documents as well as published reports and statistics.
Choroidal changes after intravitreal injection of interferon alpha-2b
Authors: Eghtedari Masoomeh , Afarid Mehrdad , Ashraf Hossein , Maalhagh Mehrnoosh 
Published: August 2019

Intravitreal injection of interferon alpha-2b (IFN-α2b) is used to treat uveitis but its effect on the choroid is unknown. We histologically evaluated the choroidal changes after intravitreal injection of IFN-α2b. We compared histological samples of IFN-α2b-injected eyes to eyes with lipopolysaccharide (LPS)-induced uveitis and eyes injected with balanced salt solution (BSS) as controls. Rabbit eyes received intravitreal injections of BSS, IFN-α2b, or LPS, and enucleation was done seven days later. Choroidal changes were evaluated on histological cut sections. The thickness of the choroid was measured in micrometer and the severity of inflammation was scored. The mean maximum choroidal thickness was significantly greater in the IFN-α2b group in comparison to the LPS and BSS groups ( P < 0.001). The mean minimum choroidal thickness was also significantly greater in the IFN group compared to the BSS group ( P = 0.009). The observed changes were mainly due to vasodilation rather than interstitial fluid retention or inflammation. Mild inflammatory cell infiltration was observed in the choroid of four eyes in the IFN group and of three eyes in the LPS group. No inflammation was seen in the control group. The difference in inflammatory cell infiltration between the LPS and IFN groups was not statistically significant. Significant choroidal hyperemia was present after injection of IFN-α2b. This fact may suggest for some pharmacological applications of IFN-α2b when increased choroidal circulation is needed. However, further studies are required to elucidate the mechanisms involved.Impact statementType I interferons are proteins that are naturally secreted by cells in response to certain stimuli. They are approved for medical use to regulate immune responses in many disease states. Our findings of increased choroidal circulation after treatment of the eye with interferon alpha-2b indicate a possible effect of this cytokine on blood circulation. This is a novel finding that needs further investigation to elucidate mechanisms and applications.
Therapeutic effects of statins on chromosomal DNA damage of dyslipidemic patients
Authors: Donmez-Altuntas Hamiyet , Bayram Fahri , Coskun-Demirkalp Ayse N , Baspınar Osman , Kocer Derya , Toth Peter P 
Published: August 2019

Statins are a group of cholesterol lowering drugs and frequently used in the therapy of dyslipidemia. Our knowledge of the impact of statin therapy on DNA damage is as yet rudimentary. In this study, we aimed to assess the possible (1) genotoxic, cytostatic, and cytotoxic effects of statins in peripheral blood lymphocytes by using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay, and (2) oxidative DNA damage by measuring plasma 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels in response to statin therapy. Thirty patients with dyslipidemia who had no chronic diseases and did not use any medicines that interfere lipid values and twenty control subjects were included in the study. Statin therapy was initiated at risk-stratified doses. Blood samples were taken before and after treatment with statins and from control subjects, and CBMN-cyt assay parameters and 8-OHdG levels were evaluated. The chromosomal DNA damage (micronuclei and nucleoplasmic bridges [NPBs]), cytostasis (nuclear division index [NDI]), and cytotoxicity (apoptotic and necrotic cell frequencies) were decreased in patients with dyslipidemia after statin treatment. No significant differences were found for 8-OHdG levels between patients with dyslipidemia before or after statin therapy. The total cholesterol and low-density lipoprotein-cholesterol levels showed positive correlations with NPB frequency in patients with dyslipidemia prior to statin treatment. The present study is the first to evaluate CBMN-cyt assay biomarkers and 8-OHdG levels in patients with dyslipidemia before and after treatment with statins. The observed reductions of chromosomal DNA damage and NDI values with statin treatment could represent an important and under-appreciated pleiotropic effect of these agents. Impact statement In literature, it is possible to find some in vitro cytokinesis-block micronucleus (CBMN) assay studies about human lymphocytes and statins. But, there are no data on CBMN-cytome (CBMN-cyt) assay parameters related to statin therapy in patients with dyslipidemia. The present study is the first to evaluate CBMN-cyt assay biomarkers and 8-OHdG levels in patients with dyslipidemia before treatment and after treatment with statins (5–10 mg/day rosuvastatin or 10–20 mg/day atorvastatin). In this study we show that statin therapy decreased chromosomal DNA damage (micronuclei and nucleoplasmic bridges) and nuclear division index (NDI) values in patients with dyslipidemia by possible molecular reasons independent of oxidative DNA damage. In addition, the decrease of chromosomal DNA damage and NDI values with statin treatment could be indicated by the association between statin use and reduced risk of cancer.
Participants’ experiences of and perceived value regarding different support types for long-term condition self-management programmes
Authors: Hughes Stephen , Lewis Sophie , Willis Karen , Rogers Anne , Wyke Sally , Smith Lorraine 
Published: August 2019

Objectives Health professional-led group programmes are a common form of long-term condition self-management support. Much research has focused on clinical outcomes of group participation, yet there is limited research on how group participants perceive and experience the support they receive. We aim to identify the different types of support that participants receive from both facilitators and other participants, and how they value this support. Methods Semi-structured interviews were conducted with 20 participants taking part in a self-management group programme for a long-term condition (obesity, type 2 diabetes or chronic obstructive pulmonary disease). Data pertaining to support types were deductively identified through a social support framework prior to interpretive thematic analysis. Results Participants identified information and emotional support from both facilitators and other participants as complementary yet distinct. Facilitators’ support came from professional training and other participants’ support reflected the contextual, lived experience. Professional interactions were prioritised, constraining opportunities for participant–participant support to be received and exchanged. Discussion We identified a key gap in how self-management support is enacted in groups. Engaging participants to share experiential knowledge will make group support more relevant and mutually beneficial to participants living with a long-term condition.
Multiplanar reformation computed tomography for carpal malalignment
Authors: Schormans Philip M. J. , Schots Judith P. M. , Weijers René E. , Loeffen Daan V. , Poeze Martijn , Hannemann Pascal F. W. 
Published: August 2019

Correct interpretation of scaphoid axial length and carpal malalignment is difficult owing to the complex geometry of the scaphoid. Traditional measurements, such as the scapholunate angle and radiolunate angle, have shown limited reproducibility. To improve the assessment of these measurements, we used multiplanar reformation computed tomography with added average intensity projection. Four measurements for scaphoid morphology and carpal alignment were independently measured by four observers on computed tomography scans of 39 consecutive patients who were treated conservatively for scaphoid fracture. Fleiss’s kappa for categorical results showed substantial agreement for the measurements of the scapholunate and radiolunate angles. Intraclass correlation coefficients were significant for measurements of the axial length, scapholunate angle and radiolunate angle. Our results suggest that multiplanar reformation computed tomography with added average intensity projection is a reliable technique for assessment of scaphoid morphology and carpal alignment. Level of evidence: II