bluuebunny/crossref_metadata_2025 huggingface dataset:
Angioplasty for the treatment of left brachiocephalic vein aneurysm: a case report
Authors: Gui Long , Xu Hongbo , Ning Chengdong , Huang Niuliu , Pan Yu
Published: March 2021

Background

Brachiocephalic vein aneurysm is a rare vascular malformation, which is often reported in case reports. At present it has attracted much attention due to the serious complications, such as vein aneurysm rupture, pulmonary embolism, venous thrombosis, etc. We report a case of left brachiocephalic vein aneurysm with compression symptoms.

Case presentation

a 52-year-old male who was admitted to our hospital with irritating cough for more than 1 month. Chest contrast-enhanced CT showed a localized expansion of 5.2 cm in diameter of the left brachiocephalic vein in the anterior mediastinum. The patient received venous angioplasty with brachiocephalic vein aneurysm resection, and the postoperative recovery was well.

Conclusion

Surgical operation is an effecive treatment method for brachiocephalic vein aneurysm, but it is still necessary to choose the appropriate way according to the type, size, location, lesion scope and complications of the vein aneurysm.
Discrepancy of p16 immunohistochemical expression and HPV RNA in penile cancer. A multiplex in situ hybridization/immunohistochemistry approach study
Authors: Zito Marino Federica , Sabetta Rosalaura , Pagliuca Francesca , Brunelli Matteo , Aquino Gabriella , Perdonà Sisto , Botti Gerardo , Facchini Gaetano , Fiorentino Francesco , Di Lauro Giovanni , De Sio Marco , De Vita Ferdinando , Toni Giorgio , Borges Dos Reis Rodolfo , Neder Luciano , Franco Renato
Published: March 2021

Background

The high-risk human papillomavirus (HPV) infection represents one of the main etiologic pathways of penile carcinogenesis in approximately 30–50 % of cases. Several techniques for the detection of HPV are currently available including Polymerase chain reaction-based techniques, DNA and RNA in situ hybridization (ISH), p16 immunohistochemistry (IHC). The multiplex HPV RNA ISH/p16 IHC is a novel technique for the simultaneous detection of HPV E6/E7 transcripts and p16INK4a overexpression on the same slide in a single assay. The main aim of this study was to evaluate the discrepancy of p16 IHC expression relatively to HPV RNA ISH in penile cancer tissue.

Methods

We collected a series of 60 PCs. HPV has been analysed through the RNA ISH, p16 IHC and the multiplex HPV RNA ISH/p16 IHC.

Results

The multiplex HPV RNA ISH /p16 IHC results in the series were in complete agreement with the previous results obtained through the classic p16 IHC and HPV RNA scope carried out on two different slides. The multiplex HPV RNA ISH /p16 IHC showed that HPV positivity in our series is more frequently in usual squamous cell carcinoma than in special histotypes (19 out of 60 − 15 %- versus 6 out of 60 − 10 %-), in high-grade than in moderate/low grade carcinomas (6 out of 60 − 10 %- versus 4 out of 60 − 6.7 %-). In addition, our data revealed that in 5 out of 20 cases with p16 high intensity expression is not associated with HPV RNA ISH positivity.

Conclusions

Our findings emphasize that the use of p16 as a surrogate of HPV positivity was unsuccessful in approximatively 8 % of cases analysed in our series. Indeed, p16 IHC showed a sensitivity of 100 % and a specificity of 71 %, with a positive predictive value (PPV) of 54 % and a negative predictive value of 100 %; when considering high intensity, p16 IHC showed a sensitivity of 100 %, a specificity of 89 %, with a PPV of 75 % and NPV of 100 %.

Since HPV positivity could represent a relevant prognostic and predictive value, the correct characterization offered by this approach appears to be of paramount importance.
Projection-dependent heterogeneity of cerebellar granule cell calcium responses
Authors: Rhee Jun Kyu , Park Heeyoun , Kim Taegon , Yamamoto Yukio , Tanaka-Yamamoto Keiko
Published: March 2021

Cerebellar granule cells (GCs) relay mossy fiber (MF) inputs to Purkinje cell dendrites via their axons, the parallel fibers (PFs), which are individually located at a given sublayer of the molecular layer (ML). Although a certain degree of heterogeneity among GCs has been recently reported, variability of GC responses to MF inputs has never been associated with their most notable structural variability, location of their projecting PFs in the ML. Here, we utilize an adeno-associated virus (AAV)-mediated labeling technique that enables us to categorize GCs according to the location of their PFs, and compare the Ca2+ responses to MF stimulations between three groups of GCs, consisting of either GCs having PFs at the deep (D-GCs), middle (M-GCs), or superficial (S-GCs) sublayer. Our structural analysis revealed that there was no correlation between position of GC soma in the GC layer and location of its PF in the ML, confirming that our AAV-mediated labeling was important to test the projection-dependent variability of the Ca2+ responses in GCs. We then found that the Ca2+ responses of D-GCs differed from those of M-GCs. Pharmacological experiments implied that the different Ca2+ responses were mainly attributable to varied distributions of GABAA receptors (GABAARs) at the synaptic and extrasynaptic regions of GC dendrites. In addition to GABAAR distributions, amounts of extrasynaptic NMDA receptors appear to be also varied, because Ca2+ responses were different between D-GCs and M-GCs when glutamate spillover was enhanced. Whereas the Ca2+ responses of S-GCs were mostly equivalent to those of D-GCs and M-GCs, the blockade of GABA uptake resulted in larger Ca2+ responses in S-GCs compared with D-GCs and M-GCs, implying existence of mechanisms leading to more excitability in S-GCs with increased GABA release. Thus, this study reveals MF stimulation-mediated non-uniform Ca2+ responses in the cerebellar GCs associated with the location of their PFs in the ML, and raises a possibility that combination of inherent functional variability of GCs and their specific axonal projection contributes to the information processing through the GCs.
Impaired pattern separation in Tg2576 mice is associated with hyperexcitable dentate gyrus caused by Kv4.1 downregulation
Authors: Kim Kyung-Ran , Kim Yoonsub , Jeong Hyeon-Ju , Kang Jong-Sun , Lee Sang Hun , Kim Yujin , Lee Suk-Ho , Ho Won-Kyung
Published: March 2021

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that causes memory loss. Most AD researches have focused on neurodegeneration mechanisms. Considering that neurodegenerative changes are not reversible, understanding early functional changes before neurodegeneration is critical to develop new strategies for early detection and treatment of AD. We found that Tg2576 mice exhibited impaired pattern separation at the early preclinical stage. Based on previous studies suggesting a critical role of dentate gyrus (DG) in pattern separation, we investigated functional changes in DG of Tg2576 mice. We found that granule cells in DG (DG-GCs) in Tg2576 mice showed increased action potential firing in response to long depolarizations and reduced 4-AP sensitive K+-currents compared to DG-GCs in wild-type (WT) mice. Among Kv4 family channels, Kv4.1 mRNA expression in DG was significantly lower in Tg2576 mice. We confirmed that Kv4.1 protein expression was reduced in Tg2576, and this reduction was restored by antioxidant treatment. Hyperexcitable DG and impaired pattern separation in Tg2576 mice were also recovered by antioxidant treatment. These results highlight the hyperexcitability of DG-GCs as a pathophysiologic mechanism underlying early cognitive deficits in AD and Kv4.1 as a new target for AD pathogenesis in relation to increased oxidative stress.
MTSplice predicts effects of genetic variants on tissue-specific splicing
Authors: Cheng Jun , Çelik Muhammed Hasan , Kundaje Anshul , Gagneur Julien
Published: March 2021

We develop the free and open-source model Multi-tissue Splicing (MTSplice) to predict the effects of genetic variants on splicing of cassette exons in 56 human tissues. MTSplice combines MMSplice, which models constitutive regulatory sequences, with a new neural network that models tissue-specific regulatory sequences. MTSplice outperforms MMSplice on predicting tissue-specific variations associated with genetic variants in most tissues of the GTEx dataset, with largest improvements on brain tissues. Furthermore, MTSplice predicts that autism-associated de novo mutations are enriched for variants affecting splicing specifically in the brain. We foresee that MTSplice will aid interpreting variants associated with tissue-specific disorders.
Homopolish: a method for the removal of systematic errors in nanopore sequencing by homologous polishing
Authors: Huang Yao-Ting , Liu Po-Yu , Shih Pei-Wen
Published: March 2021

Nanopore sequencing has been widely used for the reconstruction of microbial genomes. Owing to higher error rates, errors on the genome are corrected via neural networks trained by Nanopore reads. However, the systematic errors usually remain uncorrected. This paper designs a model that is trained by homologous sequences for the correction of Nanopore systematic errors. The developed program, Homopolish, outperforms Medaka and HELEN in bacteria, viruses, fungi, and metagenomic datasets. When combined with Medaka/HELEN, the genome quality can exceed Q50 on R9.4 flow cells. We show that Nanopore-only sequencing can produce high-quality microbial genomes sufficient for downstream analysis.
Assessment of remifentanil for rapid sequence induction and intubation in patients at risk of pulmonary aspiration of gastric contents compared to rapid-onset paralytic agents: study protocol for a non-inferiority simple blind randomized controlled trial (the REMICRUSH study)
Authors: Grillot Nicolas , Garot Matthias , Lasocki Sigismond , Huet Olivier , Bouzat Pierre , Le Moal Charlène , Oudot Mathieu , Chatel-Josse Nolwenn , El Amine Younes , Danguy des Déserts Marc , Bruneau Nathalie , Cinotti Raphael , David Jean-Stéphane , Langeron Olivier , Minville Vincent , Tching-Sin Martine , Faurel-Paul Elodie , Lerebourg Céline , Flattres-Duchaussoy Delphine , Jobert Alexandra , Asehnoune Karim , Feuillet Fanny , Roquilly Antoine
Published: March 2021

Background

Rapid-onset paralytic agents are recommended to achieve muscle relaxation and facilitate tracheal intubation during rapid sequence induction in patients at risk of pulmonary aspiration of gastric contents. However, opioids are frequently used in this setting. The study’s objective is to demonstrate the non-inferiority of remifentanil compared to rapid-onset paralytic agents, in association with an hypnotic drug, for tracheal intubation in patients undergoing  procedure under general anesthesia and at risk of pulmonary aspiration of gastric contents.

Methods

The REMICRUSH (Remifentanil for Rapid Sequence Induction of Anaesthesia) study is a multicenter, single-blinded, non-inferiority randomized controlled trial comparing remifentanil (3 to 4 μg/kg) with rapid-onset paralytic agents (succinylcholine or rocuronium 1 mg/kg) for rapid sequence induction in 1150 adult surgical patients requiring tracheal intubation during general anesthesia. Enrolment started in October 2019 in 15 French anesthesia units. The expected date of the final follow-up is October 2021. The primary outcome is the proportion of successful tracheal intubation without major complications. A non-inferiority margin of 7% was chosen. Analyses of the intent-to-treat and per-protocol populations are planned.

Discussion

The REMICRUSH trial protocol has been approved by the ethics committee of The Comité de Protection des Personnes Sud-Ouest et Outre-Mer II and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals. The REMICRUSH trial is the first randomized controlled trial powered to investigate whether remifentanil with hypnotics is non-inferior to rapid-onset paralytic agents with hypnotic in rapid sequence induction of anesthesia for full stomach patients considering successful tracheal intubation without major complication.

Trial registration

ClinicalTrials.gov NCT03960801. Registered on May 23, 2019.
Clinical study on the effect of multifocal contact lenses on myopia progression in myopia school children
Authors: Hieda Osamu , Nakamura Yo , Hiraoka Takahiro , Kojima Miho , Oshika Tetsuro , Sotozono Chie
Published: March 2021

Background

The efficacy of peripheral low add multifocal soft contact lenses (SCLs) for suppressing the progression of myopia is controversial. The aim of the on-going present clinical study is to investigate whether or not multifocal SCLs with + 0.50 diopters (D) addition suppress the progression of myopia in myopic elementary school children.

Design

Prospective randomized controlled trial.

Subjects and methods

The study plans to include a total of 100 myopic school children. Target subjects are primary school male and female students with mild to moderate myopia. Children who have eye-related diseases other than myopia are excluded from the study, because they may affect the evaluation of the outcome. Subjects will be randomly assigned to wear daily disposable multifocal contact lenses with + 0.50D addition or daily disposable SCLs. Subjects will wear contact lenses on both eyes and will be observed for 2 years under a double-masked examination. Primary outcome is a change in the axial length over the 2-year period.

Objectives

The purpose of this study is to identify whether or not multifocal SCLs with + 0.5D addition suppress the progression of myopia in myopic elementary school children as compared with standard SCLs.

Trial registration

1. UMIN (University Hospital Medical Information Network) UMIN000027940. Registered on July 21, 2017

2. JRCT (Japan Registry of Clinical Trials) jRCTs052180172. Registered on March 26, 2019
Promising proteins detected by Western blot from Echinococcus granulosus protoscoleces for predicting early post-surgical outcomes in CE-affected Tunisian children
Authors: Salah Eya Ben , Barrera Coralie , Mosbahi Sana , Gottstein Bruno , Siles-Lucas Mar , Belhassen Samia , Nouri Abdellatif , BABBA Hamouda , Millon Laurence , Sakly Wahiba
Published: March 2021

Background

Cystic echinococcosis (CE) affects predominantly young patients in highly endemic areas. Improved serological methods are needed for the follow-up of CE cases, especially given the high rates of post-surgical relapse that require detection as soon as possible.

Methods

We designed a study to investigate the value of antigenic proteins extracted fromEchinococcus granulosus(E. granulosus) protoscoleces, and of recombinant B2t and 2B2t proteins, for assessing the efficacy of surgical treatment carried out on CE-affected children. This study was performed on 278 plasma samples collected from 59 Tunisian children surgically treated for CE and monitored for 3 years post-surgery. The patients were classified according to post-surgical outcomes into a “non-relapsed” (NRCE) and a “relapsed” (RCE) group. We performed in-house ELISAs to measure anti-B2t and anti-2B2t IgG and immunoblotting for the detection of IgG against SDS-PAGE-resolvedE. granulosusprotoscoleces-specific antigens. The Wilcoxon test was applied to assess anti-B2t and anti-2B2t IgG levels. We applied the Cochran Q test to compare the distribution of immunoblotting antigenic bands between 1-month and 1-year post-surgery.

Results

The probability of being “relapse-free” when a decrease in antibody titers occurred between 1 month and 1 year post-surgery was 81% and 75%, respectively, for anti-B2t and anti-2B2t IgG. We identified five protoscolex protein bands of 20, 26/27, 30, 40 and 46 kDa as highly immunoreactive by immunoblot for both RCE and NRCE patients at 1 month post-surgery, and significantly lower immunoreactivity after 1 year (p < 10–4) for NRCE compared to RCE patients. The proteins at 26/27 and 40 kDa displayed the best performance in predicting the outcome, with an 84% probability of being relapse-free when the reactivity against the 40 kDa antigen, the doublet at 26/27 kDa, or both was absent or disappeared between 1 month and 1 year post-surgery, and a 93% probability of being relapsed when both bands remained reactive or increased in intensity between the two time points.

Conclusions

The B2t protein could be useful for the prediction of CE early post-surgical outcomes. The proteins ofE. granulosusprotoscoleces, especially the doublet P26/27 and P40, could be promising predictive biomarkers for the post-surgical follow-up of CE cases as well.

Graphical Abstract
The role of pharmacy in the management of cardiometabolic risk, metabolic syndrome and related diseases in severe mental illness: a mixed-methods systematic literature review
Authors: Sud Dolly , Laughton Eileen , McAskill Robyn , Bradley Eleanor , Maidment Ian
Published: March 2021

Background

Individuals with severe mental illness, e.g. schizophrenia have up to a 20% shortened life expectancy compared to the general population. Cardiovascular disease, due to cardiometabolic risk and metabolic syndrome, accounts for most of this excess mortality. A scoping search revealed that there has not been a review of published studies on the role of pharmacy in relation to cardiometabolic risk, metabolic syndrome and related diseases (e.g. type 2 diabetes) in individuals with severe mental illness.

Methods

A mixed-methods systematic review was performed. Eleven databases were searched using a comprehensive search strategy to identify English-language studies where pharmacy was involved in an intervention for cardiometabolic risk, metabolic syndrome or related diseases in severe mental illness in any study setting from any country of origin. First, a mapping review was conducted. Then, implementation strategies used to implement the study intervention were classified using the Cochrane Effective Practice and Organisation of Care Taxonomy. Impact of the study intervention on the process (e.g. rate of diagnosis of metabolic syndrome) and clinical (e.g. diabetic control) outcomes were analysed where possible (statistical tests of significance obtained for quantitative outcome parameters reported). Quality assessment was undertaken using a modified Mixed Methods Appraisal Tool.

Results

A total of 33 studies were identified. Studies were heterogeneous for all characteristics. A total of 20 studies reported quantitative outcome data that allowed for detailed analysis of the impact of the study intervention. The relationship between the total number of implementation strategies used and impact on outcomes measured is unclear. Inclusion of face-to-face interaction in implementation of interventions appears to be important in having a statistically significantly positive impact on measured outcomes even when used on its own. Few studies included pharmacy staff in community or general practitioner practices (n = 2), clinical outcomes, follow up of individuals after implementation of interventions (n = 3). No studies included synthesis of qualitative data.

Conclusions

Our findings indicate that implementation strategies involving face-to-face interaction of pharmacists with other members of the multidisciplinary team can improve process outcomes when used as the sole strategy. Further work is needed on clinical outcomes (e.g. cardiovascular risk reduction), role of community pharmacy and qualitative studies.

Systematic review registration

PROSPERO CRD42018086411
Using concave optimization methods for inexact quadratic programming problems with an application to waste management
Authors: Mahajan Sumati , Gupta S. K. , Ahmad Izhar , Al-Homidan S.
Published: March 2021

Quadratic programming is potentially capable of strategic decision making in real world problems. However, practical problems rarely conform to crisp parameters, and hence the prospects of these problems with inexact parameters are inevitably higher. The existing studies regarding public welfare schemes/ organizations reveal that their objectives end up as minimization of cost functions and are governed by linear or concave quadratic programming problems. The present study proposes a method that can be applied to concave type quadratic objective function subject to linear constraints with inexact parameters. A comparison is also drawn with existing methods to establish its simplicity and efficiency. Further, a numerical example is illustrated, and finally, a waste management problem is formulated and solved using the proposed method.
Biochar’s effect on the ecosystem services provided by sandy-textured and contaminated sandy soils: a systematic review protocol
Authors: Bekchanova Madina , Campion Luca , Bruns Stephan , Kuppens Tom , Jozefczak Marijke , Cuypers Ann , Malina Robert
Published: March 2021

Background

Biochar is a relatively new soil amendment method in agricultural practices that can improve the ecosystem services of soils. Biochar has commonly been applied to less fertile or contaminated soils, specifically sandy-textured and contaminated sandy soils, to improve their properties. However, the available literature indicates that not all sandy-textured and contaminated sandy soils show the same response to biochar applications, as the sign and size of the effect vary across studies. More specifically, primary studies show heterogeneous and potentially conflicting impacts of biochar application on a set of ecosystem services provided by these types of soils; namely, biomass production, water cycle, nutrient cycle, and climate regulation. Therefore, the objective of the present study is to systematically review the available evidence base to synthesise the impact and drivers of biochar amendments on four specific ecosystem services provided by sandy-textured and contaminated sandy soils.

Methods

This review follows the guideline of the Collaboration for Environmental Evidence and corresponds to the ROSES (RepOrting standards for Systematic Evidence Synthesis) reporting standard. A comprehensive search strategy will be employed to cover peer-reviewed and gray literature through bibliographic databases, organizational and institutional websites, and web searches. Search terms and strategies have been developed to identify the impact of biochar on the ecosystem services of sandy-textured soils. The search results will be screened first by their title and abstract, and then by their full text. Two literature reviewers will do this based on eligibility criteria. A validity assessment will be conducted to critically appraise and assess the validity of studies using a common validity framework for environmental studies. Data will be extracted from the studies that are found to be valid for the review. Narrative synthesis and meta-analysis will be employed to synthesise the review results.
ANCA-associated vasculitis overlaps with systemic sclerosis: a case report and literature review
Authors: Wu Rui , Su Jiang , Zou Yu-rong , Zhu Jing
Published: March 2021

Background

Systemic sclerosis (SSc) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) both affect the kidney and may cause renal failure. Treatment of AAV is dramatically different from that of SSc renal crisis (SRC). Kidney biopsy is not recommended for diagnosing SRC, but it is the only reliable diagnostic method for AAV.

Case presentation

Here, a 49-year-old male patient with diffuse SSc presented with acute renal insufficiency and detectable ANCA with myeloperoxidase-specific antibodies. A renal biopsy revealed necrotizing glomerulonephritis and was consistent with AAV. This finding confirms the existence of AAV and SSc overlap syndrome. The patient was treated with intravenous methylprednisolone, intravenous cyclophosphamide, tandem membrane plasma exchange, and hemodialysis. After treatment, his clinical symptoms remained stable, and his creatinine and C-reactive protein (CRP) levels have remained normalized as of his most recent follow-up after hospital discharge.

Conclusions

AAV can overlap with SSc; although this condition is rare, it is associated with considerable morbidity and mortality. Therefore, it is critical to recognize AAV in the setting of worsening renal function due to SSs and provide appropriate treatment. Several clinical features are suggestive of AAV rather than SRC, but renal biopsy is required for accurate diagnosis.
PCSK9 promotes tumor growth by inhibiting tumor cell apoptosis in hepatocellular carcinoma
Authors: Zhang Shi-Zhe , Zhu Xiao-Dong , Feng Long-Hai , Li Xiao-Long , Liu Xue-Feng , Sun Hui-Chuan , Tang Zhao-You
Published: March 2021

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key enzymes in the process of lipid transport, is involved in the disease progression of various types of tumors. This article is to study the role of PCSK9 in the progression of hepatocellular carcinoma (HCC).

Methods

Immunohistochemistry was used to assess the expression of PCSK9 in tumor specimens from 105 HCC patients who underwent curative resection. Western blotting and quantitative real-time PCR were used to test the protein and mRNA expression levels in HCC cell lines. Cell Counting Kit-8 (CCK-8) and clone formation assays were performed to evaluate the proliferation ability of different kinds of cells in vitro. Flow cytometry was used to analyze cell cycle distribution and apoptosis rate. A xenograft model was established to study the effect of PCSK9 on HCC growth in vivo. TUNEL and immunofluorescence assays were used to detect cell apoptosis.

Results

High expression of PCSK9 in tumor tissues was related to microvascular invasion (p = 0.036) and large tumor size (p = 0.001) in HCC patients. Overall survival and disease-free survival after surgery were poor in patients with high expression of PCSK9 (p = 0.035 and p = 0.007, respectively). In vivo and in vitro experiments showed that PCSK9 promoted the growth of HCC by inhibiting cell apoptosis. A mechanistic study revealed that PCSK9 increases FASN expression, thereby inhibiting apoptosis of HCC cells via the Bax/Bcl-2/Caspase9/Caspase3 pathway.

Conclusions

PCSK9 expression level in HCC is an indicator of poor prognosis for patients with HCC. FASN-mediated anti-apoptosis plays an important role in PCSK9-induced HCC progression.
The impact of social complexity on the visual exploration of others' actions in preschoolers with autism spectrum disorder
Authors: Robain F. , Kojovic N. , Solazzo S. , Glaser B. , Franchini M. , Schaer M.
Published: March 2021

Background

Typical development of socio-communicative skills relies on keen observation of others. It thus follows that decreased social attention negatively impacts the subsequent development of socio-communicative abilities in children with autism spectrum disorders (ASD). In addition, studies indicate that social attention is modulated by context and that greater social difficulties are observed in more socially demanding situations. Our study aims to investigate the effect of social complexity on visual exploration of others’ actions in preschoolers.

Methods

To investigate the impact of social complexity, we used an eye-tracking paradigm with 26 typically developing preschoolers (TD, age = 3.60 ± 1.55) and 37 preschoolers with ASD (age = 3.55 ± 1.21). Participants were shown videos of two children engaging in socially simple play (parallel) versus socially complex play (interactive). We subsequently quantified the time spent and fixation duration on faces, objects, bodies, as well as the background and the number of spontaneous gaze shifts between socially relevant areas of interest.

Results

In the ASD group, we observed decreased time spent on faces. Social complexity (interactive play) elicited changes in visual exploration patterns in both groups. From the parallel to the interactive condition, we observed a shift towards socially relevant parts of the scene, a decrease in fixation duration, as well as an increase in spontaneous gaze shifts between faces and objects though there were fewer in the ASD group.

Limitations

Our results need to be interpreted cautiously due to relatively small sample sizes and may be relevant to male preschoolers, given our male-only sample and reported phenotypic differences between males and females.

Conclusion

Our results suggest that similar to TD children, though to a lesser extent, visual exploration patterns in ASD are modulated by context. Children with ASD that were less sensitive to context modulation showed decreased socio-communicative skills or higher levels of symptoms. Our findings support using naturalistic designs to capture socio-communicative deficits in ASD.
The future of meniscus science: international expert consensus
Authors: DePhillipo Nicholas N. , LaPrade Robert F. , Zaffagnini Stefano , Mouton Caroline , Seil Romain , Beaufils Philippe
Published: March 2021

Purpose

The purpose of this study was to evaluate the main focus areas for research and development for furthering the state of meniscus science in 2021.

Methods

An electronic survey including 10 questions was sent in a blind fashion to the faculty members of the 5th International Conference on Meniscus Science and Surgery. These faculty served as an expert consensus on the future of research and development areas of meniscus science. Survey responses were analyzed using descriptive statistics and ranking weighted averages were calculated to score survey questions.

Results

Of the 82 faculty, 76 (93%) from 18 different countries completed the survey (84% male, 16% female). The highest ranked future research and development focus areas were meniscus repair, biologics, osteotomy procedures, addressing meniscus extrusion, and the development of new therapies for the prevention of posttraumatic osteoarthritis. Currently, the most ‘valuable’ type of biologic reported for meniscus treatment was platelet-rich plasma. The main reported global research limitation was a lack of long-term clinical outcomes data. The most promising emerging medical technologies for improving meniscus science were 3-D printing, personalized medicine, and artificial implants.

Conclusions

This survey suggests that the future of meniscus science should be focused on meniscal preservation techniques through meniscus repair, addressing meniscal extrusion, and the use of orthobiologics. The lack of long-term clinical outcomes was the main reported research limitation globally for meniscus treatment. Future product development utilizing emerging medical technologies suggest the use of 3-D printing for meniscal transplants/scaffolds, personalized treatment, and bioengineering for artificial implants.

Level of Evidence

Level V.
Cybersecurity challenges in energy sector (virtual power plants) - can edge computing principles be applied to enhance security?
Authors: Venkatachary Sampath Kumar , Alagappan Annamalai , Andrews Leo John Baptist
Published: March 2021

Distributed generators (D.G.’s) enable us to generate, supply and be self-reliant on power while also allows us to supply power to meet the demand through virtual power plants. The virtual power plants also help us analyse, control, optimise, and help bridge the gap of demand and supply in these vast energy requirements. With this also comes challenges associated with securing physical systems, data protection and information privacy. Recent technological advancements have aided cybercriminals to disrupt operations by carrying out deliberate attacks on the energy sector. Though security researchers have tried to mitigate the risks, vulnerabilities, and it remains a challenge. This paper aims to present a comprehensive Edge-based security architecture to help reduce the risks and help secure the physical systems and ensure privacy and data protection.
Precision time protocol attack strategies and their resistance to existing security extensions
Authors: Alghamdi Waleed , Schukat Michael
Published: March 2021

The IEEE 1588 precision time protocol (PTP) is very important for many industrial sectors and applications that require time synchronization accuracy between computers down to microsecond and even nanosecond levels. Nevertheless, PTP and its underlying network infrastructure are vulnerable to cyber-attacks, which can stealthily reduce the time synchronization accuracy to unacceptable and even damage-causing levels for individual clocks or an entire network, leading to financial loss or even physical destruction. Existing security protocol extensions only partially address this problem. This paper provides a comprehensive analysis of strategies for advanced persistent threats to PTP infrastructure, possible attacker locations, and the impact on clock and network synchronization in the presence of security protocol extensions, infrastructure redundancy, and protocol redundancy. It distinguishes between attack strategies and attacker types as described in RFC7384, but further distinguishes between the spoofing and time source attack, the simple internal attack, and the advanced internal attack. Some experiments were conducted to demonstrate the impact of PTP attacks. Our analysis shows that a sophisticated attacker has a range of methodologies to compromise a PTP network. Moreover, all PTP infrastructure components can host an attacker, making the comprehensive protection of a PTP network against a malware infiltration, as for example exercised by Stuxnet, a very tedious task.
Stopping “transient ischemic attacks” by antiplatelet withdrawal
Authors: Palaiodimou Lina , Theodorou Aikaterini , Lachanis Stefanos , Paraskevas George P. , Papathanasiou Matilda , Zompola Christina , Voumvourakis Konstantinos I. , Tsivgoulis Georgios
Published: March 2021

Introduction

Transient ischemic attack (TIA) is considered to be an important risk factor for the development of ischemic stroke and requires complete etiopathogenic evaluation and prompt initiation of secondary prevention treatment. In addition, an accurate differential diagnosis should be performed in order to exclude other disorders mimicking TIA.

Methods

In this case report, we describe the clinical and neuroimaging evaluation and the differential diagnosis of a patient with suspected crescendo TIAs.

Results

A 79-year-old man presented with recurrent episodes of right-sided numbness over the past 7 months, despite different single and dual antiplatelet therapies that were sequentially prescribed for suspected TIAs. Brain MRI revealed cortical superficial siderosis, symmetrical periventricular leukoencephalopathy and enlarged perivascular spaces. Cerebral amyloid angiopathy was considered in the differential diagnosis of the patient. Antiplatelet withdrawal was recommended and led to complete remission of the patient’s transient focal neurological episodes (TFNE) that were initially misdiagnosed as TIAs.

Discussion

Cortical superficial siderosis has been implicated as a key neuroimaging feature of cerebral amyloid angiopathy, a diagnosis which can be supported by the additional radiological findings of symmetrical white matter hyperintensities and enlarged perivascular spaces. Antiplatelet treatment in patients with cortical superficial siderosis may increase the frequency and severity of TFNE, while it increases exponentially the risk of intracerebral hemorrhage. The present case highlights that recognition of cortical superficial siderosis is crucial in the management of patients presenting with transient focal neurological symptoms that can be misdiagnosed as recurrent TIAs.
Non-ST elevation acute coronary syndromes; clinical landscape, management strategy and in-hospital outcomes: an age perspective
Authors: Dakhil Zainab Atiyah , Farhan Hasan Ali
Published: March 2021

Background

As the elderly represent a substantial proportion of medical care beneficiaries, and there is limited data about age disparity in emerging countries, this study sought to investigate the impact of age on the management in patients with non-ST elevation acute coronary syndromes (NSTE-ACS).

Results

Two hundred patients with NSTE-ACS enrolled prospectively, patients’ data, pharmacotherapy, management strategy as well timing to catheterization were documented. Patients grouped into ≥ 65 years versus < 65 years; 32.5% were ≥ 65-year-old. The older group presented as high GRACE risk (Global Registry of Acute Coronary Events) (67.7% versus 15.6%). Elderly patients were less likely to be referred for catheterization compared with younger counterparts (55.4% versus 76.3%, p = 0.003). Within low risk class patients, none of the elderly versus 9.33% of younger patients were catheterized within 2 h; in the same line, none of the elderly versus 16% of younger patients were catheterized within 24 h. Alternatively, at high risk class, 6.81% of the elderly and none of the younger patients were catheterized within 2 h. On the univariate analysis of variables to predict invasive strategy, presence of history of prior IHD, diabetes, absent in-hospital acute heart failure or atrial fibrillation/flutter, higher haemoglobin and lower creatinine levels predicted the use of invasive strategy, while on multivariate analysis, acute heart failure (95% CI − 0.38 to − 0.41, p = 0.01), lower haemoglobin (95% CI 0.002–0.07, p = 0.03), and atrial fibrillation/flutter (95% CI − 0.48 to − 0.02, p = 0.03) predicted conservative strategy. The elderly were more likely to have acute heart failure (32.3% versus 14.8%, p = 0.004), same as stroke (3.1% versus none, p = 0.04).

Conclusions

Less-invasive strategy used in the elderly with NSTE-ACS compared with younger counterparts, yet age was not a predictor of catheterization underuse on multivariate analysis. It is crucial to bridge the age gap in the healthcare system in setting of ACS management by grasping the attention of decision makers and emphasizing on the adherence of healthcare providers to the guidelines to improve cardiovascular care and outcomes.
Coronary tortuosity relation with carotid intima-media thickness, coronary artery disease risk factors, and diastolic dysfunction: is it a marker of early atherosclerosis?
Authors: Elamragy Ahmed , Yakoub Samuel , AbdelGhany Mohamed , Ammar Waleed
Published: March 2021

Background

Coronary tortuosity (C-Tor) is a common finding in coronary angiography (CAG). There are conflicting data about its link to atherosclerosis: one study found a negative relationship with coronary artery disease (CAD), although it had been linked to age and hypertension (HTN), which are CAD risk factors. Carotid intima-media thickness (C-IMT) is a measure of early atherosclerosis and a surrogate for CAD, diastolic dysfunction is also associated with CAD risk factors. In this retrospective case-control study, we investigated the relationship between C-Tor, C-IMT, diastolic dysfunction, and the other risk factors in patients undergoing CAG in a tertiary hospital between July 2017 and June 2018, after excluding patients with significant CAD. C-Tor was defined as the presence of ≥ 3 bends (≥ 45°) along the trunk of at least one main coronary artery in CAG.

Results

After excluding 663 patients due to exclusion criteria, 30 patients with C-Tor were compared with age and gender-matched controls. HTN was significantly more common in the C-Tor group (86.7% vs. 30%, p < 0.002); other clinical characteristics were similar. The C-IMT was abnormal in the C-Tor group only (p: 0.007). The diastolic dysfunction parameters differed between the two groups: the E/A ratio was < 1 in the C-Tor group and > 1 in the normal group (p: < 0.001); the E velocity and deceleration time were significantly lower in the C-Tor group (p: 0.001 and < 0.001 respectively); the E/E′ ratio, A, and A′ velocities were significantly higher (p: 0.005, < 0.001, < 0.001 respectively); while the S′ velocity was similar in the 2 groups (p: 0.078). The C-Tor group had higher total cholesterol and LDL (p: 0.003 and 0.006 respectively). All C-Tor patients undergoing stress tests had positive results. The only independent C-Tor predictors in a regression analysis were HTN, total cholesterol, A-wave velocity, and deceleration time (DT) (odds ratio: 14.7, 1.03, 1.15, and 0.95, all p: < 0.05). A-wave velocity had the best area under the curve, sensitivity, and specificity for C-Tor prediction (0.88, 73.3%, and 96.7% respectively) followed by DT (0.86, 66.67%, and 96.6% respectively).

Conclusion

C-Tor is associated with increased C-IMT, HTN, hyperlipidemia, and left ventricular diastolic dysfunction; all contributing to an ongoing atherosclerotic process. A-wave velocity and DT were independent predictors of C-Tor. C-Tor may cause microvascular ischemia that merits further investigation.
Q-chains in the U(1)-gauged Friedberg-Lee-Sirlin model
Authors: Loiko V. , Perapechka I. , Shnir Ya.
Published: March 2021

We construct static axially symmetric multi-Q-ball configurations in the U(1)-gauged two-component Fridberg-Lee-Sirlin model in a flat spacetime. The solutions represent electromagnetically bounded chains of stationary spinning charged Q-balls placed along the axis of symmetry. We discuss the properties of these configurations and exhibit their domain of existence.
Basal Ganglia Calcification Is Associated With Local and Systemic Metabolic Mechanisms in Adult Hypoparathyroidism
Authors: Zavatta Guido , Tebben Peter J , McCollough Cynthia H , Yu Lifeng , Vrieze Thomas , Clarke Bart L
Published: March 2021

Context

Hypoparathyroidism is characterized by low serum calcium, increased serum phosphorus, and inappropriately low or decreased serum parathyroid hormone, which may be associated with soft tissue calcification in the basal ganglia of the brain.

Objective

To assess the prevalence and factors involved in the pathophysiology of basal ganglia calcification (BGC) in the brain in chronic hypoparathyroidism and to evaluate proposed pathophysiologic mechanisms.

Design

Case-control study with retrospective review of medical records over 20 years.

Setting

Single academic medical center.

Patients

142 patients with chronic hypoparathyroidism and computed tomography (CT) head scans followed between January 1, 2000 and July 9, 2020, and 426 age- and sex-matched controls with CT head scans over the same interval.

Interventions

None.

Main Outcome Measures

Demographic, biochemical, and CT head imaging findings, with semiquantitative assessment of volumetric BGC.

Results

The study found that 25.4% of 142 patients followed for a median of 17 years after diagnosis of chronic hypoparathyroidism had BGC, which developed at a younger age than in controls. BGC was 5.1-fold more common in nonsurgical patients and less common in postsurgical patients. Low serum calcium and low calcium/phosphate ratio correlated with BGC. Neither serum phosphorus nor calcium × phosphate product predicted BGC. Lower serum calcium was associated with greater volume of BGC. The extent of BGC varied widely, with nonsurgical patients generally having a greater volume and distribution of calcification.

Conclusions

BGC is associated with low serum calcium and low serum calcium/phosphate ratio, which may be related to severity of the disease, its etiology, or duration of treatment.
Should I Stay or Should I Go? CRHPVN Neurons Gate State Transitions in Stress-Related Behaviors
Authors: Daviu Nuria , Bains Jaideep S
Published: March 2021

Corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus are the canonical controllers of the endocrine response to stress. Here we propose a new role for these cells as a gate for state transitions that allow the organism to engage in stress-related behaviors. Specifically, we review evidence indicating that activation of these cells at critical times allows organisms to move to a state that is permissive for motor action. This is evident when the organism is under duress (defensive behavior), when the organism has successfully vanquished a threat (coping behavior), and when an organism initiates approach to a conspecific (social behavior). The motor behavior that follows from the activation of CRH neurons is not necessarily under the control of these cells but is determined by higher order circuits that discriminate more refined features of environmental context to execute the appropriate behavior.
Normal and Premature Adrenarche
Authors: Rosenfield Robert L
Published: March 2021

Adrenarche is the maturational increase in adrenal androgen production that normally begins in early childhood. It results from changes in the secretory response to adrenocorticotropin (ACTH) that are best indexed by dehydroepiandrosterone sulfate (DHEAS) rise. These changes are related to the development of the zona reticularis (ZR) and its unique gene/enzyme expression pattern of low 3ß-hydroxysteroid dehydrogenase type 2 with high cytochrome b5A, sulfotransferase 2A1, and 17ß-hydroxysteroid dehydrogenase type 5. Recently 11-ketotestosterone was identified as an important bioactive adrenarchal androgen. Birth weight, body growth, obesity, and prolactin are related to ZR development. Adrenarchal androgens normally contribute to the onset of sexual pubic hair (pubarche) and sebaceous and apocrine gland development. Premature adrenarche causes ≥90% of premature pubarche (PP). Its cause is unknown. Affected children have a significantly increased growth rate with proportionate bone age advancement that typically does not compromise growth potential. Serum DHEAS and testosterone levels increase to levels normal for early female puberty. It is associated with mildly increased risks for obesity, insulin resistance, and possibly mood disorder and polycystic ovary syndrome. Between 5% and 10% of PP is due to virilizing disorders, which are usually characterized by more rapid advancement of pubarche and compromise of adult height potential than premature adrenarche. Most cases are due to nonclassic congenital adrenal hyperplasia. Algorithms are presented for the differential diagnosis of PP. This review highlights recent advances in molecular genetic and developmental biologic understanding of ZR development and insights into adrenarche emanating from mass spectrometric steroid assays.
Tumor Shrinkage by Metyrapone in Cushing Disease Exhibiting Glucocorticoid-Induced Positive Feedback
Authors: Tsujimoto Yasutaka , Shichi Hiroki , Fukuoka Hidenori , Yamamoto Masaaki , Sato Itsuko , Imanishi Takamitsu , Nakamura Tomoaki , Inoshita Naoko , Ishida Atsushi , Yamada Shozo , Takahashi Yutaka , Chihara Kazuo
Published: March 2021

Context

Paradoxical increases in serum cortisol in the dexamethasone suppression test (DST) have been rarely observed in Cushing disease (CD). Its pathophysiology and prevalence remain unclear.

Case Description

A 62-year-old woman with suspected CD showed paradoxical increases in cortisol after both 1-mg and 8-mg DST (1.95-fold and 2.52-fold, respectively). The initiation of metyrapone paradoxically decreased plasma adrenocorticotropic hormone (ACTH) levels and suppressed cortisol levels. Moreover, the pituitary tumor considerably shrank during metyrapone treatment.

Ex Vivo Experiments

The resected tumor tissue was enzymatically digested, dispersed, and embedded into Matrigel as 3D cultured cells. ACTH levels in the media were measured. In this tumor culture, ACTH levels increased 1.3-fold after dexamethasone treatment (P < 0.01) while control tumor cultures exhibited no increase in ACTH levels, but rather a 20% to 40% suppression (P < 0.05).

Clinical Study

A cross-sectional, retrospective, multicenter study that included 92 patients with CD who underwent both low-dose and high-dose DST from 2014 to 2020 was performed. Eight cases (8.7%) showed an increase in serum cortisol after both low-dose and high-dose DST.

Conclusion

This is the first report of a patient with glucocorticoid (GC)-driven positive feedback CD who showed both ACTH suppression and tumor shrinkage by metyrapone. Our cohort study revealed that 8.7% of patients with CD patients possibly possess GC-driven positive-feedback systems, thereby suggesting the presence of a new subtype of CD that is different from the majority of CD cases. The mechanisms exhibiting GC positive feedback in CD and the therapeutic approach for these patients remain to be investigated.