bluuebunny/crossref_metadata_2025 huggingface dataset:
TMEM63C mutations cause mitochondrial morphology defects and underlie hereditary spastic paraplegia
Authors: Tábara Luis Carlos , Al-Salmi Fatema , Maroofian Reza , Al-Futaisi Amna Mohammed , Al-Murshedi Fathiya , Kennedy Joanna , Day Jacob O , Courtin Thomas , Al-Khayat Aisha , Galedari Hamid , Mazaheri Neda , Protasoni Margherita , Johnson Mark , Leslie Joseph S , Salter Claire G , Rawlins Lettie E , Fasham James , Al-Maawali Almundher , Voutsina Nikol , Charles Perrine , Harrold Laura , Keren Boris , Kunji Edmund R S , Vona Barbara , Jelodar Gholamreza , Sedaghat Alireza , Shariati Gholamreza , Houlden Henry , Crosby Andrew H , Prudent Julien , Baple Emma L
Published: April 2022

The hereditary spastic paraplegias (HSP) are among the most genetically diverse of all Mendelian disorders. They comprise a large group of neurodegenerative diseases that may be divided into ‘pure HSP’ in forms of the disease primarily entailing progressive lower-limb weakness and spasticity, and ‘complex HSP’ when these features are accompanied by other neurological (or non-neurological) clinical signs. Here, we identified biallelic variants in the transmembrane protein 63C (TMEM63C) gene, encoding a predicted osmosensitive calcium-permeable cation channel, in individuals with hereditary spastic paraplegias associated with mild intellectual disability in some, but not all cases. Biochemical and microscopy analyses revealed that TMEM63C is an endoplasmic reticulum-localized protein, which is particularly enriched at mitochondria–endoplasmic reticulum contact sites. Functional in cellula studies indicate a role for TMEM63C in regulating both endoplasmic reticulum and mitochondrial morphologies. Together, these findings identify autosomal recessive TMEM63C variants as a cause of pure and complex HSP and add to the growing evidence of a fundamental pathomolecular role of perturbed mitochondrial-endoplasmic reticulum dynamics in motor neurone degenerative diseases.
Cholinergic neurotransmitter system: a potential marker for post-stroke cognitive recovery
Authors: Geranmayeh Fatemeh
Published: April 2022

This scientific commentary refers to ‘Cholinergic and hippocampal systems facilitate cross-domain cognitive recovery after stroke’ by O’Sullivan et al. (https://doi.org/10.1093/brain/awac070).
Non-severe burn injury increases cancer incidence in mice and has long-term impacts on the activation and function of T cells
Authors: Barrett Lucy W , Fear Vanessa S , Foley Bree , Audsley Katherine , Barnes Samantha , Newnes Hannah , McDonnell Alison , Wood Fiona M , Fear Mark W , Waithman Jason
Published: April 2022

Background

Recent evidence suggests that burn patients are at increased risk of hospital admission for infection, mental health conditions, cardiovascular disease and cancer for many years after discharge for the burn injury itself. Burn injury has also been shown to induce sustained immune system dysfunction. This change to immune function may contribute to the increased risk of chronic disease observed. However, the mechanisms that disrupt long-term immune function in response to burn trauma, and their link to long-term morbidity, remain unknown. In this study we investigated changes to immune function after burn injury using a murine model of non-severe injury.

Methods

An established mouse model of non-severe burn injury (full thickness burn equivalent to 8% total body surface area) was used in combination with an orthotopic model of B16 melanoma to investigate the link between burns and cancer. Considering that CD8+ T cells are important drivers of effective tumour suppression in this model, we also investigated potential dysregulation of this immune population using mouse models of burn injury in combination with herpes simplex virus infection. Flow cytometry was used to detect and quantify cell populations of interest and changes in immune function.

Results

We demonstrate that 4 weeks after a non-severe burn injury, mice were significantly more susceptible to tumour development than controls using an orthotopic model of B16 melanoma. In addition, our results reveal that CD8+ T cell expansion, differentiation and memory potential is significantly impaired at 1 month post-burn.

Conclusions

Our data suggests that CD8+ T cell-mediated immunity may be dysfunctional for a sustained period after even non-severe burn injury. Further studies in patients to validate these findings may support clinical intervention to restore or protect immunity in patients after burn injury and reduce the increased risk of secondary morbidities observed.
Organization and engagement of a prefrontal-olfactory network during olfactory selective attention
Authors: Cansler Hillary L , in ’t Zandt Estelle E , Carlson Kaitlin S , Khan Waseh T , Ma Minghong , Wesson Daniel W
Published: April 2022

Background

Sensory perception is profoundly shaped by attention. Attending to an odor strongly regulates if and how it is perceived – yet the brain systems involved in this process are unknown. Here we report integration of the medial prefrontal cortex (mPFC), a collection of brain regions integral to attention, with the olfactory system in the context of selective attention to odors.

Methods

First, we used tracing methods to establish the tubular striatum (TuS, also known as the olfactory tubercle) as the primary olfactory region to receive direct mPFC input in rats. Next, we recorded (i) local field potentials from the olfactory bulb (OB), mPFC, and TuS, or (ii) sniffing, while rats completed an olfactory selective attention task.

Results

Gamma power and coupling of gamma oscillations with theta phase were consistently high as rats flexibly switched their attention to odors. Beta and theta synchrony between mPFC and olfactory regions were elevated as rats switched their attention to odors. Finally, we found that sniffing was consistent despite shifting attentional demands, suggesting that the mPFC-OB theta coherence is independent of changes in active sampling.

Conclusions

Together, these findings begin to define an olfactory attention network wherein mPFC activity, as well as that within olfactory regions, are coordinated based upon attentional states.
Adolescent social isolation shifts the balance of decision-making strategy from goal-directed action to habitual response in adulthood via suppressing the excitatory neurotransmission onto the direct pathway of the dorsomedial striatum
Authors: Shan Qiang , Yu Xiaoxuan , Tian Yao
Published: April 2022

Adverse experience, such as social isolation, during adolescence is one of the major causes of neuropsychiatric disorders that extend from adolescence into adulthood, such as substance addiction, obsessive–compulsive disorder, and eating disorders leading to obesity. A common behavioral feature of these neuropsychiatric disorders is a shift in the balance of decision-making strategy from goal-directed action to habitual response. This study has verified that adolescent social isolation directly shifts the balance of decision-making strategy from goal-directed action to habitual response, and that it cannot be reversed by simple regrouping. This study has further revealed that adolescent social isolation induces a suppression in the excitatory neurotransmission onto the direct-pathway medium spiny neurons of the dorsomedial striatum (DMS), and that chemogenetically compensating this suppression effect shifts the balance of decision-making strategy from habitual response back to goal-directed action. These findings suggest that the plasticity in the DMS causes the shift in the balance of decision-making strategy, which would potentially help to develop a general therapy to treat the various neuropsychiatric disorders caused by adolescent social isolation. Such a study is especially necessary under the circumstances that social distancing and lockdown have caused during times of world-wide, society-wide pandemic.
Resolving heterogeneity in obsessive–compulsive disorder through individualized differential structural covariance network analysis
Authors: Han Shaoqiang , Xu Yinhuan , Guo Hui-Rong , Fang Keke , Wei Yarui , Liu Liang , Cheng Junying , Zhang Yong , Cheng Jingliang
Published: April 2022

Background

The high heterogeneity of obsessive–compulsive disorder (OCD) denies attempts of traditional case–control studies to derive neuroimaging biomarkers indicative of precision diagnosis and treatment.

Methods

To handle the heterogeneity, we uncovered subject-level altered structural covariance by adopting individualized differential structural covariance network (IDSCN) analysis. The IDSCN measures how structural covariance edges in a patient deviated from those in matched healthy controls (HCs) yielding subject-level differential edges. One hundred patients with OCD and 106 HCs were recruited and whose T1-weighted anatomical images were acquired. We obtained individualized differential edges and then clustered patients into subtypes based on these edges.

Results

Patients presented tremendously low overlapped altered edges while frequently shared altered edges within subcortical–cerebellum network. Two robust neuroanatomical subtypes were identified. Subtype 1 presented distributed altered edges while subtype 2 presented decreased edges between default mode network and motor network compared with HCs. Altered edges in subtype 1 predicted the total Yale-Brown Obsessive Compulsive Scale score while that in subtype 2 could not.

Conclusions

We depict individualized structural covariance aberrance and identify that altered connections within subcortical–cerebellum network are shared by most patients with OCD. These 2 subtypes provide new insights into taxonomy and facilitate potential clues to precision diagnosis and treatment of OCD.
Activity-dependent feedback regulation of thalamocortical axon development by Lhx2 in cortical layer 4 neurons
Authors: Wang Chia-Fang , Yang Jenq-Wei , Zhuang Zi-Hui , Hsing Hsiang-Wei , Luhmann Heiko J , Chou Shen-Ju
Published: April 2022

Establishing neuronal circuits requires interactions between pre- and postsynaptic neurons. While presynaptic neurons were shown to play instructive roles for the postsynaptic neurons, how postsynaptic neurons provide feedback to regulate the presynaptic neuronal development remains elusive. To elucidate the mechanisms for circuit formation, we study the development of barrel cortex (the primary sensory cortex, S1), whose development is instructed by presynaptic thalamocortical axons (TCAs). In the first postnatal weeks, TCA terminals arborize in layer (L) 4 to fill in the barrel center, but it is unclear how TCA development is regulated. Here, we reported that the deletion of Lhx2 specifically in the cortical neurons in the conditional knockout (cKO) leads to TCA arborization defects, which is accompanied with deficits in sensory-evoked and spontaneous cortical activities and impaired lesion-induced plasticity following early whisker follicle ablation. Reintroducing Lhx2 back in L4 neurons in cKO ameliorated TCA arborization and plasticity defects. By manipulating L4 neuronal activity, we further demonstrated that Lhx2 induces TCA arborization via an activity-dependent mechanism. Additionally, we identified the extracellular signaling protein Sema7a as an activity-dependent downstream target of Lhx2 in regulating TCA branching. Thus, we discovered a bottom-up feedback mechanism for the L4 neurons to regulate TCA development.
Effectiveness of Messenger RNA Coronavirus Disease 2019 Vaccines Against Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections During the Delta Variant Epidemic in Japan: Vaccine Effectiveness Real-time Surveillance for SARS-CoV-2 (VERSUS)
Authors: Maeda Haruka , Saito Nobuo , Igarashi Ataru , Ishida Masayuki , Suami Kazuya , Yagiuchi Ai , Kimura Yuya , Komino Masaru , Arai Hiromi , Morikawa Toru , Motohashi Iori , Miyazawa Rei , Moriyama Tetsu , Kamura Hiroshi , Terada Mayumi , Kuwamitsu Osamu , Hayakawa Tomoichiro , Sando Eiichiro , Ohara Yasuji , Teshigahara Osamu , Suzuki Motoi , Morimoto Konosuke
Published: April 2022

Background

Although high vaccine effectiveness of messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines has been reported in studies in several countries, data are limited from Asian countries, especially against the Delta (B.1.617.2) variant.

Methods

We conducted a multicenter test-negative case-control study in patients aged ≥16 years visiting hospitals or clinics with signs or symptoms consistent with COVID-19 from 1 July to 30 September 2021, when the Delta variant was dominant (≥90% of SARS-CoV-2 infections) nationwide in Japan. Vaccine effectiveness of BNT162b2 or mRNA-1273 against symptomatic SARS-CoV-2 infections was evaluated. Waning immunity among patients aged 16–64 years was also assessed.

Results

We enrolled 1936 patients, including 396 test-positive cases and 1540 test-negative controls for SARS-CoV-2. The median age was 49 years, 53.4% were male, and 34.0% had underlying medical conditions. Full vaccination (receiving 2 doses ≥14 days before symptom onset) was received by 6.6% of cases and 38.8% of controls. Vaccine effectiveness of full vaccination against symptomatic SARS-CoV-2 infections was 88.7% (95% confidence interval [CI], 78.8%–93.9%) among patients aged 16–64 years and 90.3% (95% CI, 73.6%–96.4%) among patients aged ≥65 years. Among patients aged 16–64 years, vaccine effectiveness was 91.8% (95% CI, 80.3%–96.6%) within 1–3 months after full vaccination, and 86.4% (95% CI, 56.9%–95.7%) within 4–6 months.

Conclusions

mRNA COVID-19 vaccines had high effectiveness against symptomatic SARS-CoV-2 infections in Japan during July–September 2021, when the Delta variant was dominant nationwide.
Financialisation of monetary policy in a dollarised economy: the case of Georgia
Authors: Eradze Ia
Published: April 2022

This paper examines the financialisation of monetary policy—articulated as inflation targeting—and provides insight on the implications this phenomenon has on dollarised economies. The analysis provided has been developed via a thorough investigation into these dynamics in the country of Georgia: a neoliberal and foreign direct investment (FDI)-led accumulation regime with an open capital account, where the inflow of foreign capital led to enhanced lending by foreign-owned banks in foreign currency and encouraged persistent dollarisation. This paper contributes to the literature on the role of foreign capital in developing economies, and the volatilities of these economies in terms of overvalued exchange rates, capital flight and rise of public debt. This paper concludes that the financialisation of monetary policy has encouraged the process of dollarisation in Georgia. The use of inflation targeting was an ineffective strategy for Georgia’s dollarised economy due to the primacy of price stability over currency stability, the reduction of the capacity of Georgia’s central bank as well as increased economic influence of foreign-owned commercial banks.
Is the China Effect Real? Ideational Change and the Political Contestation of Chinese State-Led Investment in Europe
Authors: Babić Milan , Dixon Adam D
Published: April 2022

Chinese outward investment is increasing in its relevance for the global economy, and its effects on host states are increasingly being scrutinized globally. While European policy-making was ambiguous about the question of hosting Chinese state-led investment (CSLI) in the early 2010s, we can observe a recent surge of protectionist legal measures across Europe. What explains this trend among different European countries? Through the lens of incremental ideational change, we hypothesize that the rise of China as a global investor shifts the perceptions of policy-makers away from being a source of investment toward a potential threat to national security. We argue that this China effect affects advanced European economies similarly. We provide evidence by studying the shift in perceptions among policy-makers in a coordinated and a liberal market economy, Germany and the UK. By drawing on document analysis and expert interviews, we unpack the policy processes in both countries in the last decade. Despite being two dissimilar cases, both show a similar outcome in increasingly curbing CSLI on the grounds of national security reasons. Our results add important insights to recent International Political Economy discussions on the “geopoliticization” of European trade and investment rules in the face of a rising China.
Diagnostic Performance of Metagenomic Next-Generation Sequencing in Pediatric Patients: A Retrospective Study in a Large Children’s Medical Center
Authors: Tao Yue , Yan Hui , Liu Yujie , Zhang Fang , Luo Lijuan , Zhou Yajuan , An Kang , Yang Ruwen , Yang Bin , Xu Teng , Xie Li , Ren Hong , Xu Zhuoming , Cao Qing , Mo Xi
Published: April 2022

Background

Metagenomic next-generation sequencing (mNGS) has the potential to become a complementary, if not essential, test in some clinical settings. However, the clinical application of mNGS in a large population of children with various types of infectious diseases (IDs) has not been previously evaluated.

Methods

From April 2019 to April 2021, 640 samples were collected at a single pediatric hospital and classified as ID [479 (74.8%)], non-ID [NID; 156 (24.4%)], and unknown cases [5 (0.8%)], according to the final clinical diagnosis. We compared the diagnostic performance in pathogen detection between mNGS and standard reference tests.

Results

According to final clinical diagnosis, the sensitivity and specificity of mNGS were 75.0% (95% CI: 70.8%–79.2%) and 59.0% (95% CI: 51.3%–66.7%), respectively. For distinguishing ID from NID, the sensitivity of mNGS was approximately 45.0% higher than that of standard tests (75.0% vs 30.0%; P < 0.001). For fungal detection, mNGS showed positive results in 93.0% of cases, compared to 43.7% for standard tests (P < 0.001). Diagnostic information was increased in respiratory system samples through the addition of meta-transcriptomic sequencing. Further analysis also showed that the read counts in sequencing data were highly correlated with clinical diagnosis, regardless of whether infection was by single or multiple pathogens (Kendall’s tau b = 0.484, P < 0.001).

Conclusions

For pediatric patients in critical condition with suspected infection, mNGS tests can provide valuable diagnostic information to resolve negative or inconclusive routine test results, differentiate ID from NID cases, and facilitate accurate and effective clinical therapeutic decision-making.
Dutch National Round Robin Trial on Plasma-Derived Circulating Cell-Free DNA Extraction Methods Routinely Used in Clinical Pathology for Molecular Tumor Profiling
Authors: van der Leest Paul , Ketelaar Emma M , van Noesel Carel J M , van den Broek Daan , van Boerdonk Robert A A , Deiman Birgit , Rifaela Naomi , van der Geize Robert , Huijsmans Cornelis J J , Speel Ernst Jan M , Geerlings Maartje J , van Schaik Ron H N , Jansen Maurice P H M , Dane-Vogelaar Ria , Driehuis Else , Leers Mathie P G , Sidorenkov Grigory , Tamminga Menno , van Kempen Léon C , Schuuring Ed
Published: April 2022

Background

Efficient recovery of circulating tumor DNA (ctDNA) depends on the quantity and quality of circulating cell-free DNA (ccfDNA). Here, we evaluated whether various ccfDNA extraction methods routinely applied in Dutch laboratories affect ccfDNA yield, ccfDNA integrity, and mutant ctDNA detection, using identical lung cancer patient–derived plasma samples.

Methods

Aliquots of 4 high-volume diagnostic leukapheresis plasma samples and one artificial reference plasma sample with predetermined tumor-derived mutations were distributed among 14 Dutch laboratories. Extractions of ccfDNA were performed according to local routine standard operating procedures and were analyzed at a central reference laboratory for mutant detection and assessment of ccfDNA quantity and integrity.

Results

Mutant molecule levels in extracted ccfDNA samples varied considerably between laboratories, but there was no indication of consistent above or below average performance. Compared to silica membrane–based methods, samples extracted with magnetic beads–based kits revealed an overall lower total ccfDNA yield (−29%; P < 0.0001) and recovered fewer mutant molecules (−41%; P < 0.01). The variant allelic frequency and sample integrity were similar. In samples with a higher-than-average total ccfDNA yield, an augmented recovery of mutant molecules was observed.

Conclusions

In the Netherlands, we encountered diversity in preanalytical workflows with potential consequences on mutant ctDNA detection in clinical practice. Silica membrane–based methodologies resulted in the highest total ccfDNA yield and are therefore preferred to detect low copy numbers of relevant mutations. Harmonization of the extraction workflow for accurate quantification and sensitive detection is required to prevent introduction of technical divergence in the preanalytical phase and reduce interlaboratory discrepancies.
Improvement of MADRL Equilibrium Based on Pareto Optimization
Authors: Zhao Zhiruo , Cao Lei , Chen Xiliang , Lai Jun , Zhang Legui
Published: April 2022

In order to solve the incalculability caused by the issue of inconsistent objective functions in multi-agent deep reinforcement learning, the concept of Nash equilibrium is introduced. However, a Marko game may have multiple equilibriums, how to filter out a stable and optimal one is worth studying. Besides solution concept, how to keep the balance between exploration and exploitation is another key issue in reinforcement learning. On basis of the methods, which can converge to Nash equilibrium, this paper makes improvement through Pareto optimization. In order to alleviate the problem of over fitting caused by Pareto optimization and non-convergence caused by strategy change, we use stratified sampling in place of random sampling as assistance. What’s more, our methods are trained through fictitious self-play to make full of self-learning experiences. By analyzing the experiment carried out on MAgent platform, the proposed methods are not only far better than traditional methods, but also reaching or even surpassing the state of art MADRL methods.
Resistance Distances In Simplicial Networks
Authors: Zhu Mingzhe , Xu Wanyue , Zhang Zhongzhi , Kan Haibin , Chen Guanrong
Published: April 2022

It is well known that in many real networks, such as brain networks and scientific collaboration networks, there exist higher order nonpairwise relations among nodes, i.e. interactions between more than two nodes at a time. This simplicial structure can be described by simplicial complexes and has an important effect on topological and dynamical properties of networks involving such group interactions. In this paper, we study analytically resistance distances in iteratively growing networks with higher order interactions characterized by the simplicial structure that is controlled by a parameter $q$. We derive exact formulas for interesting quantities about resistance distances, including Kirchhoff index, additive degree-Kirchhoff index, multiplicative degree-Kirchhoff index, as well as average resistance distance, which have found applications in various areas elsewhere. We show that the average resistance distance tends to a $q$-dependent constant, indicating the impact of simplicial organization on the structural robustness measured by average resistance distance.
3D Flattering Amplified Neural Network-Based Segmentation of Amygdala and Hippocampus
Authors: Smitha J C , Jane Ambily , Chandran Lekshmi
Published: April 2022

Recent emergence in deep learning resulted in significant improvement in the segmentation accuracy of sub cortical brain structures like hippocampus and amygdala. The traditional methods of segmentation cannot produce an ideal segmentation result that exhibits issues like redundant computations, inconsistencies, coefficient variations and motion artifacts. Therefore, in this paper, an improved 3D Flatteringly Amplified Neural Network model for biomedical imaging is efficiently proposed, which can make full use of the 3D spatial information of MRI image itself to overcome the inconsistency of segmented images along with equalizing the coefficient variation of tiny region of brain image segmentation. Also while equalizing the coefficient, certain significant minute details are lost due to motion artifacts hence, the robust Amyg-Hippo Seg algorithm has been introducing that extracts the features through deep learning, and achieve high-precision segmentation, it reduced the computational complexity without neglecting minute features. In addition, the Daytona dropout function provides uncertainty information and reduces over-fitting problems. The outcome of the proposed work efficiently segments the most significant regions of hippocampus and amygdala with 97.4% accuracy.
Intelligent Forecast of Stock Markets to Handle COVID-19 Economic Crisis by Modified Generative Adversarial Networks
Authors: Sornavalli G , Angelin Gladston , Khanna Nehemiah H
Published: April 2022

Stock markets have voluminous data and are subjected to uncertainty. The coronavirus disease of 2019 (COVID-19) pandemic has hit the stock markets and the trends of stock markets have accelerated share prices of few companies and has also brought freefall to certain companies. This factor highlights the importance of technical analysis of the stock markets over fundamental analysis. So, the proposed robust model for financial forecasting is built based on the technical indicators and the fake price data generated over a period of time from the stock dataset by a novel architecture of modified generative adversarial network, which uses a dense recurrent neural network as the generator and a dense spectrally normalized convolutional neural network as the discriminator. The hyperparameters used in the network model follow the two-time-scale-update rule and they are tuned by using the Bayesian optimization technique. The feature importance of the technical indicators in predicting the performance by the stock market is enhanced by the XGBoost algorithm. The generative adversarial networks (GAN) used for forecasting in the previous works suffer from problems like mode collapse and non-convergence. So, the proposed work concentrates on building a GAN model, which is stable, robust and converges to Nash equilibrium. The generated GAN model is applied on stock data from the major 100 companies of the S&P 500 stock for a period of 20 years. The modified GAN model predicts prices precise ~99 percentage, which maximizes the stock returns. The proposed modified GAN model outperforms the baseline GAN model and other state of the art approaches of forecasting on comparison.
The Diagnosability of Interconnection Networks with Missing Edges and Broken-Down Nodes Under the PMC and MM* Models
Authors: Guo Chen , Liu Qiuming , Xiao Zhifang , Peng Shuo
Published: April 2022

Diagnosability is often considered as an important factor for measuring the self-diagnostic ability of network systems. However, classic system-level diagnosis focuses only on processor faults and ignores the objective reality of communication faults. Under real circumstances, missing edges and node failures usually occur simultaneously in multiprocessor systems (called hybrid fault circumstances). Therefore, it is important to study the diagnosability of multiprocessor systems under hybrid fault circumstances. In this paper, we propose several diagnosabilities of interconnection networks with missing edges and faulty nodes. By exploring some important relationships between diagnosability and the minimum degree of a network under hybrid fault circumstances, we present and prove the diagnosability of several classic interconnection networks, including BC (bijective connection) networks, star graphs, folded hypercubes, exchanged hypercubes, exchanged crossed cubes, k-ary n-cubes, bubble-sort star graphs and balanced hypercubes, with missing edges and broken-down nodes under the PMC (Preparata, Metze and Chien) and MM* (Maeng and Malek) models.
Automated Computer-Aided Diagnosis of Diabetic Retinopathy Based on Segmentation and Classification using K-nearest neighbor algorithm in retinal images
Authors: Kaur Jaspreet , Kaur Prabhpreet
Published: April 2022

Diabetic retinopathy (DR) is an eye oddity where the human retina is afflicted because of the ever-increasing quantity of insulin in the blood. It leads to the loss of sight. Preliminary diagnosis of DR assists to improve to inhibit future injury. Proper DR screening has been recognized as an economical way to accumulate health services. Automated retinal analysis become known as the most significant screening approach for primitive DR diagnosis, which leads to diminishing the workload related to manual screening and also, cost-effective and less time-consuming efforts. In the proposed work, the preprocessing, removal of applicant lesion pixels, and formulation of feature set have been examined which is fully appropriate for the classification task. In preprocessing approach, the framework removes the unwanted pixels, eliminates the optic disc, and extraction of the blood vessels from the retinal images. Morphological operations are applied to extract the boundaries of the blood vessels and then 2D discrete wavelet decomposition is applied to estimate the horizontal, vertical and diagonal coefficients. The candidate lesion pixels i.e. dark and bright DR pixels are detected using an adaptive threshold that uses local statistical, geometrical, and location-based characteristics of the background image. The extracted feature set is processed using a K-nearest neighbor (KNN) classifier with 80% of training data and 20% of testing data to diagnose the severity level of the disease. The proposed scheme is evaluated by the DIARETDB1 benchmark dataset with the performance parameters, i.e. 95% of accuracy, 92.6% of sensitivity and 87.56% specificity achieved with less computation time required.
Exploring the Relationship Between Bariatric Surgery and Inflammatory Bowel Disease: A Systematic Review
Authors: Wise Journey , Plescia Trevor , Cummings Bethany Paige , Lyo Victoria
Published: April 2022

Background

Obesity affects over 40% of Americans. Bariatric surgery is an increasingly popular and well-studied method to achieve weight loss, improve metabolic homeostasis, and resolve obesity-related comorbid conditions. While the impact of bariatric surgery on weight loss and metabolic health has been extensively studied, there is an increasing body of literature characterizing the impact of bariatric surgery on gastrointestinal health and inflammation. Inflammatory bowel disease (IBD) leads to inflammation in both the small and large intestine, and leads to significant patient morbidity. Similar to obesity, the incidence of IBD is also rising. Patients with IBD and obesity may seek bariatric surgery. The impact of bariatric surgery on IBD is not well understood, but critical to understand for optimal patient care. Herein, we review the currently available literature on the impact of bariatric surgery on IBD including common trends, discrepancies in findings, and remaining knowledge gaps in need of further study.

Methods

A systematic review of the PubMed/MEDLINE database using PRISMA guidelines was performed.

Results

We identified 12 manuscripts discussing de novo IBD after bariatric surgery and 16 studying bariatric surgery in patients with pre-existing IBD. Overall, bariatric surgery appears to be safe in patients with pre-existing IBD but may increase the risk of developing de novo IBD.

Conclusions

Further research into optimal surgical approaches, patient selection, and mechanisms on how bariatric surgery impacts IBD is needed.
Neutrophil inhibition improves acute inflammation in a murine model of viral myocarditis
Authors: Carai Paolo , González Laura Florit , Van Bruggen Stijn , Spalart Valerie , De Giorgio Daria , Geuens Nadéche , Martinod Kimberly , Jones Elizabeth Anne Vincent , Heymans Stephane
Published: April 2022

Aims

Viral myocarditis (VM) is an inflammatory pathology of the myocardium triggered by a viral infection that may cause sudden death or heart failure (HF), especially in the younger population. Current treatments only stabilize and improve cardiac function without resolving the underlying inflammatory cause. The factors that induce VM to progress to HF are still uncertain, but neutrophils have been increasingly associated with the negative evolution of cardiac pathologies. The present study investigates the contribution of neutrophils to VM disease progression in different ways.

Methods and results

In a coxsackievirus B3- (CVB3) induced mouse model of VM, neutrophils and neutrophil extracellular traps (NETs) were prominent in the acute phase of VM as revealed by enzyme-linked immunosorbent assay analysis and immunostaining. Anti-Ly6G-mediated neutrophil blockade starting at model induction decreased cardiac necrosis and leucocyte infiltration, preventing monocyte and Ly6CHigh pro-inflammatory macrophage recruitment. Furthermore, genetic peptidylarginine deiminase 4-dependent NET blockade reduced cardiac damage and leucocyte recruitment, significantly decreasing cardiac monocyte and macrophage presence. Depleting neutrophils with anti-Ly6G antibodies at 7 days post-infection, after the acute phase, did not decrease cardiac inflammation.

Conclusion

Collectively, these results indicate that the repression of neutrophils and the related NET response in the acute phase of VM improves the pathological phenotype by reducing cardiac inflammation.
Long-term trends in the epidemiology of cardiovascular diseases in the UK: insights from the British Heart Foundation statistical compendium
Authors: Cheema Katherine Margaret , Dicks Ed , Pearson Jeremy , Samani Nilesh J
Published: April 2022

The British Heart Foundation’s (BHF) annual statistical compendium is a comprehensive source of accessible epidemiological data in relation to cardiovascular disease (CVD) in the UK. Using datasets with multiple years of data from the compendium we have analysed trends in mortality, morbidity, and treatment for CVD within the UK. CVD mortality in the UK has consistently declined over recent decades, from 1045 deaths per 100 000 in 1969, shortly after the BHF was founded, to 255 per 100 000 in 2019. Despite this remarkable improvement, inequalities in CVD mortality persist in the UK nations, for example in 2019 the death rate in Scotland was 326 deaths per 100 000 compared with 246 per 100 000 in England. Improvements in CVD mortality have been paralleled by increased use of primary prevention medications (anti-hypertensives and statins) and interventional procedures. In recent years, progress in mortality outcomes has stalled, probably due to a combination of factors including a rise in risk factors such as obesity and diabetes. In terms of morbidity, CVD remains a significant burden in the UK, accounting for at least 1.18 million hospital admissions and reflects the enormous economic burden of CVD, estimated at £19bn in the UK. Our results highlight the importance of accessible and comprehensive statistics in relation to the burden of CVD and the value of the BHF’s annual compendium in drawing out conclusions and opportunities for future research. One key area is to improve the data on which estimation of prevalence is based. There is also a need for ongoing work to better understand the root causes of disparity between socio-economic groups in relation to CVD. One important way to address this will be to improve the consistency of reporting of CVD health data across all nations of the UK. Understanding the causes will inform UK healthcare planning in addition to providing analytical insights that will be applicable in other countries.
Psychometric Characteristics of the Visual Communication and Sign Language Checklist
Authors: Allen Thomas E , Morere Donna A
Published: April 2022

Since its publication in 2013, the Visual Communication and Sign Language (VCSL) Checklist has been widely utilized to assess the development of early American Sign Language skills of deaf children from birth to age 5. However, little research has been published using the results of VCSL assessments. Notably, no psychometric analyses have been conducted to verify the validity of the VCSL in a population whose characteristics are different from those of the small sample of native signing children from whom the published norms were created. The current paper, using data from the online version of the VCSL (VCSL:O), addresses this shortcoming. Ratings of the 114 VCSL items from 562 evaluations were analyzed using a partial-credit Rasch model. Results indicate that the underlying skill across the age range comprises an adequate single dimension. Within the items’ age groupings, however, the dimensionality is not so clear. Item ordering, as well as item fit, is explored in detail. In addition, the paper reports the benefits of using the resulting Rasch scale scores, which, unlike the published scoring strategy that focuses on basal and ceiling performance, makes use of the ratings of partial credit, or emerging, skills. Strategies for revising the VCSL are recommended.
A Narrative Systematic Review and Categorisation of Outcomes in Inflammatory Bowel Disease to Inform a Core Outcome Set for Real-world Evidence
Authors: Wong Charlotte , van Oostrom Joep , Bossuyt Peter , Pittet Valerie , Hanzel Jurij , Samaan Mark , Tripathi Monika , Czuber-Dochan Wladyslawa , Burisch Johan , Leone Salvatore , Saldaña Roberto , Baert Filip , Kopylov Uri , Jaghult Susanna , Adamina Michel , Gecse Krisztina , Arebi Naila
Published: April 2022

Background

Heterogeneity exists in reported outcomes and outcome measurement instruments [OMI] from observational studies. A core outcome set [COS] for observational and real-world evidence [RWE] in inflammatory bowel disease [IBD] will facilitate pooling large datasets. This systematic review describes and classifies clinical and patient-reported outcomes, for COS development.

Methods

The systematic review of MEDLINE, EMBASE, and CINAHL databases identified observational studies published between 2000 and 2021 using the population exposure outcome [PEO] framework. Studies meeting eligibility criteria were included. After titles and abstracts screening, full-text articles were extracted by two independent reviewers. Primary and secondary outcomes with corresponding OMI were extracted and categorised in accordance with OMERACT Filter 2.1 framework. The frequency of outcomes and OMIs are described.

Results

From 5854 studies, 315 were included: 129 [41%] Crohn’s disease [CD], 60 [19%] ulcerative colitis [UC], and 126 [40%] inflammatory bowel disease [IBD] studies with 600 552 participants. Totals of 1632 outcomes and 1929 OMI were extracted mainly from medical therapy [181; 72%], surgical [34; 11%], and endoscopic [6; 2%] studies. Clinical and medical therapy-related safety were frequent outcome domains recorded in 194 and 100 studies. Medical therapy-related adverse events [n = 74] and need for surgery [n = 71] were the commonest outcomes. The most frequently reported OMI were patient or event numbers [n = 914], Harvey-Bradshaw Index [n = 45], and Montreal classification [n = 42].

Conclusions

There is substantial variability in outcomes reporting and OMI types. Categorised outcomes and OMI from this review will inform a Delphi consensus on a COS for future RWE in IBD. Data collection standardisation may enhance the quality of RWE applied to decision-making.
Predation and Climate Limit Establishment Success of the Kyushu Strain of the Biological Control AgentAphalara itadori(Hemiptera: Aphalaridae) in the Northeastern United States
Authors: Andersen Jeremy C , Elkinton Joseph S
Published: April 2022

Species of knotweeds, Reynoutria spp. Houtt. (Caryophyllales: Polygonaceae), including Japanese knotweed (R. japonica Houtt.), are among the most invasive and ecologically destructive plant species introduced to North America and Europe. The Kyushu strain of the psyllid Aphalara itadori Shinji (Hemiptera: Aphalaridae) has been approved as a biological control agent for release against Japanese knotweed in the United Kingdom, Canada, and the United States. However, recent reports from Canada suggest that both biotic and abiotic factors may limit its establishment. Therefore, we examined the potential role of predation by comparing open- versus closed-sleeve treatments, and climate mis-matches by collecting temperature data from release sites and performing climate suitability analyses using MaxEnt. Our results indicated that populations of the Kyushu strain could only be maintained in the field in closed-sleeve treatments, suggesting that predation is likely limiting the establishment success of this strain. In addition, we noted that daily maximum temperatures at our field sites might exceed documented developmental thresholds for this strain, and that MaxEnt species distribution modeling indicates no climate similarities between locations in eastern North America and Kyushu. Combined with previous results, our study suggests that the establishment of the Kyushu strain of A. itadori as a biological control agent for Japanese knotweed may be limited in eastern North America. We suggest that one strategy to increase the probability of establishment of the Kyushu strain could be to increase the number of release sites in an effort to find a more optimal niche with predator-free space.
Increasing Body Sizes in Anomala expansa expansa (Coleoptera: Scarabaeidae) Populations in Response to Rising Temperatures Over Time
Authors: Maher Ian M , Shelomi Matan
Published: April 2022

Many insects have been studied over wide geographical areas to determine whether they follow Bergmann’s Rule, which predicts that animal clades or populations should have smaller body sizes in warmer climates. While this ecogeographic rule is well supported in mammals and birds, insect latitudinal sizes can show Bergmann, converse Bergmann, or no size clines at all. Museum collections are typical sources of data for insect clines, and long-term collections should reflect rising global temperatures and shifting climates, possibly producing temporal size clines along with any geographical clines. We hypothesize that insects with Bergmann clines geographically will show Bergmann-like clines temporally as well, and that the converse and inverse of this rule are also true. By looking at museum samples going back a century, we tested whether Anomala expansa expansa (Bates, 1866), a species of Scarabaeidae beetle common in lowland Taiwan, was experiencing long-term changes in body size in response to rising temperatures. We found that overall, the size of these beetles increased over time. Within Taipei populations, this increase was correlated with rising average yearly temperatures. The impact of this pest species’ rising size with time will need to be monitored, and temporal size clines in other pests need to be investigated.
Incidence and predictors of mortality after an electrical storm in the ICU
Authors: Ninni Sandro , Layec Jeremy , Brigadeau François , Behal Hélène , Labreuche Julien , Klein Cédric , Schurtz Guillaume , Potelle Charlotte , Coisne Augustin , Lemesle Gilles , Lamblin Nicolas , Klug Didier , Lacroix Dominique
Published: April 2022

Aims

For assessing predictors of early mortality following hospitalization for electrical storm (ES), only limited data are available. The purpose of this study was to assess the incidence and predictors of early mortality following hospitalization in the intensive care unit (ICU) for ES in a large retrospective study.

Methods and results

In this retrospective study, we included all patients who were hospitalized for ES from July 2015 to May 2020 in our tertiary centre. A total of 253 patients were included. The median age was 66 [56; 73], and 64% had ischemic cardiomyopathy. A total of 37% of patients presented hemodynamic instability requiring catecholamine at admission. A total of 17% of patients presented an acute reversible cause for ES. The one-year mortality was 34% (95% CI, 30–43%), mostly driven by heart failure (HF). The multivariable Cox's regression model identified age, left ventricular ejection fraction, right ventricle dysfunction, haemoglobin level as independent predictors of one-year mortality. The use of catecholamine at admission was identified as the only variable related to the initial management of ES associated with an increased 30-day mortality risk (HR: 7.95 (95%CI, 3.18–19.85).

Conclusion

In patients admitted for ES in ICU, the one-year mortality remains high and mostly driven by HF. The use of catecholamine at admission is associated with a seven-fold risk for mortality within 30 days. In such patients, the potential use of VT ablation can be questioned and a careful action plan regarding invasive HF-related therapy could be considered.
Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 and 2019
Authors: Raisi-Estabragh Zahra , Kobo Ofer , Freeman Phillip , Petersen Steffen E , Kolman Louis , Miller Robert J H , Roguin Ariel , Van Spall Harriette G C , Vuong Jacqueline , Yang Eric H , Mamas Mamas A
Published: April 2022

Aims

We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site.

Methods and results

We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629 308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%).

Conclusion

We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.