bluuebunny/crossref_metadata_2025_split huggingface dataset:
DDoS Attack Detection in Edge-IIoT Network Using Ensemble Learning
Authors: Laiq Fariba , Al-Obeidat Feras , Amin Adnan , Moreira Fernando 
Published: May 2024

Abstract
As the number of IoT devices increases daily due to the rapid growth in technology, every device and network is vulnerable to attacks because it is exposed to the internet. Denial of Service (DoS) is a prevalent type of intrusion on the Internet of Things (IoT) network in which the server becomes down due to flooding requests. Distributed Denial of Service (DDoS) is a special type of DoS attack where the network of malicious computers called botnet consumes the target’s system resources by flooding the requests. Edge computing is closely related to Industrial Internet of Things (IIoT), and industry 4.0. Both of them are relatively emerging technologies so security is a crucial part of them. By incorporating our contributions to the current and innovative dataset Edge-IIoT, the proposed study presents a novel approach to detect DDoS attacks in an IIoT network in the domain of edge computing, whether the traffic is normal or malicious (DDoS traffic). This study explores various Ensemble Learning (EL) techniques to predict normal and malicious DDoS traffic along with the type of DDoS attack. The study applies various preprocessing techniques like Synthetic Minority Over Sampling Technique (SMOTE), label encoding, etc. to enhance the model’s performance and reveals how EL techniques performs better in terms of accuracy than the individual classifiers. Further, the performance of all EL techniques has been investigated in terms of all evaluation measures, including the elapsed time. This important addition not only broadens the focus of study in this area but also offers insightful comparisons of the efficiency and precision of various ensemble approaches as well as individual classifiers. The study achieved a maximum of 99.99% in all evaluation measures.
Machine-learning strategies for the accurate and efficient analysis of x-ray spectroscopy
Authors: Penfold Thomas , Watson Luke , Middleton Clelia , David Tudur , Verma Sneha , Pope Thomas , Kaczmarek Julia , Rankine Conor 
Published: May 2024

Abstract
Computational spectroscopy has emerged as a critical tool for researchers looking to achieve both qualitative and quantitative interpretations of experimental spectra. Over the past decade, increased interactions between experiment and theory have created a positive feedback loop that has stimulated developments in both domains. In particular, the increased accuracy of calculations has led to them becoming an indispensable tool for the analysis of spectroscopies across the electromagnetic spectrum. This progress is especially well demonstrated for short-wavelength techniques, e.g. core-hole (x-ray) spectroscopies, whose prevalence has increased following the advent of modern x-ray facilities including third-generation synchrotrons and x-ray free-electron lasers. While calculations based on well-established wavefunction or density-functional methods continue to dominate the greater part of spectral analyses in the literature, emerging developments in machine-learning algorithms are beginning to open up new opportunities to complement these traditional techniques with fast, accurate, and affordable ‘black-box’ approaches. This Topical Review recounts recent progress in data-driven/machine-learning approaches for computational x-ray spectroscopy. We discuss the achievements and limitations of the presently-available approaches and review the potential that these techniques have to expand the scope and reach of computational and experimental x-ray spectroscopic studies.
Predicting functional UTR variants by integrating region-specific features
Authors: Li Guangyu , Wu Jiayu , Wang Xiaoyue 
Published: May 2024

Abstract
The untranslated region (UTR) of messenger ribonucleic acid (mRNA), including the 5′UTR and 3′UTR, plays a critical role in regulating gene expression and translation. Variants within the UTR can lead to changes associated with human traits and diseases; however, computational prediction of UTR variant effect is challenging. Current noncoding variant prediction mainly focuses on the promoters and enhancers, neglecting the unique sequence of the UTR and thereby limiting their predictive accuracy. In this study, using consolidated datasets of UTR variants from disease databases and large-scale experimental data, we systematically analyzed more than 50 region-specific features of UTR, including functional elements, secondary structure, sequence composition and site conservation. Our analysis reveals that certain features, such as C/G-related sequence composition in 5′UTR and A/T-related sequence composition in 3′UTR, effectively differentiate between nonfunctional and functional variant sets, unveiling potential sequence determinants of functional UTR variants. Leveraging these insights, we developed two classification models to predict functional UTR variants using machine learning, achieving an area under the curve (AUC) value of 0.94 for 5′UTR and 0.85 for 3′UTR, outperforming all existing methods. Our models will be valuable for enhancing clinical interpretation of genetic variants, facilitating the prediction and management of disease risk.
Mutational signatures of colorectal cancers according to distinct computational workflows
Authors: Battuello Paolo , Corti Giorgio , Bartolini Alice , Lorenzato Annalisa , Sogari Alberto , Russo Mariangela , Di Nicolantonio Federica , Bardelli Alberto , Crisafulli Giovanni 
Published: May 2024

Abstract
Tumor mutational signatures have gained prominence in cancer research, yet the lack of standardized methods hinders reproducibility and robustness. Leveraging colorectal cancer (CRC) as a model, we explored the influence of computational parameters on mutational signature analyses across 230 CRC cell lines and 152 CRC patients. Results were validated in three independent datasets: 483 endometrial cancer patients stratified by mismatch repair (MMR) status, 35 lung cancer patients by smoking status and 12 patient-derived organoids (PDOs) annotated for colibactin exposure. Assessing various bioinformatic tools, reference datasets and input data sizes including whole genome sequencing, whole exome sequencing and a pan-cancer gene panel, we demonstrated significant variability in the results. We report that the use of distinct algorithms and references led to statistically different results, highlighting how arbitrary choices may induce variability in the mutational signature contributions. Furthermore, we found a differential contribution of mutational signatures between coding and intergenic regions and defined the minimum number of somatic variants required for reliable mutational signature assignment. To facilitate the identification of the most suitable workflows, we developed Comparative Mutational Signature analysis on Coding and Extragenic Regions (CoMSCER), a bioinformatic tool which allows researchers to easily perform comparative mutational signature analysis by coupling the results from several tools and public reference datasets and to assess mutational signature contributions in coding and non-coding genomic regions. In conclusion, our study provides a comparative framework to elucidate the impact of distinct computational workflows on mutational signatures.
Klinefelter syndrome: etiology and clinical considerations in male infertility
Authors: Chen Xinyue , Zhang Xueguang , Jiang Ting , Xu Wenming 
Published: May 2024

Abstract
Klinefelter syndrome (KS) is the most prevalent chromosomal disorder occurring in males. It is defined by an additional X chromosome, 47,XXY, resulting from errors in chromosomal segregation during parental gametogenesis. A major phenotype is impaired reproductive function, in the form of low testosterone and infertility. This review comprehensively examines the genetic and physiological factors contributing to infertility in KS, in addition to emergent assisted reproductive technologies, and the unique ethical challenges KS patients face when seeking infertility treatment. The pathology underlying KS is increased susceptibility for meiotic errors during spermatogenesis, resulting in aneuploid or even polyploid gametes. Specific genetic elements potentiating this susceptibility include polymorphisms in checkpoint genes regulating chromosomal synapsis and segregation. Physiologically, the additional sex chromosome also alters testicular endocrinology and metabolism by dysregulating interstitial and Sertoli cell function, collectively impairing normal sperm development. Additionally, epigenetic modifications like aberrant DNA methylation are being increasingly implicated in these disruptions. We also discuss assisted reproductive approaches leveraged in infertility management for KS patients. Application of assisted reproductive approaches, along with deep comprehension of the meiotic and endocrine disturbances precipitated by supernumerary X chromosomes, shows promise in enabling biological parenthood for KS individuals. This will require continued multidisciplinary collaboration between experts with background of genetics, physiology, ethics, and clinical reproductive medicine.
Inference for possibly misspecified generalized linear models with nonpolynomial-dimensional nuisance parameters
Authors: Hong Shaoxin , Jiang Jiancheng , Jiang Xuejun , Wang Haofeng 
Published: May 2024

Summary
It is routine practice in statistical modelling to first select variables and then make inference for the selected model as in stepwise regression. Such inference is made upon the assumption that the selected model is true. However, without this assumption, one would not know the validity of the inference. Similar problems also exist in high-dimensional regression with regularization. To address these problems, we propose a dimension-reduced generalized likelihood ratio test for generalized linear models with nonpolynomial dimensionality, based on quasilikelihood estimation that allows for misspecification of the conditional variance. The test has nearly oracle performance when using the correct amount of shrinkage and has robust performance against the choice of regularization parameter across a large range. We further develop an adaptive data-driven dimension-reduced generalized likelihood ratio test and prove that, with probability going to one, it is an oracle generalized likelihood ratio test. However, in ultrahigh-dimensional models the penalized estimation may produce spuriously important variables that deteriorate the performance of the test. To tackle this problem, we introduce a cross-fitted dimension-reduced generalized likelihood ratio test, which is not only free of spurious effects, but robust against the choice of regularization parameter. We establish limiting distributions of the proposed tests. Their advantages are highlighted via theoretical and empirical comparisons to some competitive tests. An application to breast cancer data illustrates the use of our proposed methodology.
Spinal cord neurone loss and foot placement changes in a rat knock-in model of amyotrophic lateral sclerosis Type 8
Authors: Murage Brenda , Tan Han , Mashimo Tomoji , Jackson Mandy , Skehel Paul A 
Published: May 2024

Abstract
Amyotrophic lateral sclerosis is an age-dependent cell type–selective degenerative disease. Genetic studies indicate that amyotrophic lateral sclerosis is part of a spectrum of disorders, ranging from spinal muscular atrophy to frontotemporal dementia that share common pathological mechanisms. Amyotrophic lateral sclerosis Type 8 is a familial disease caused by mis-sense mutations in VAPB. VAPB is localized to the cytoplasmic surface of the endoplasmic reticulum, where it serves as a docking point for cytoplasmic proteins and mediates inter-organelle interactions with the endoplasmic reticulum membrane. A gene knock-in model of amyotrophic lateral sclerosis Type 8 based on the VapBP56S mutation and VapB gene deletion has been generated in rats. These animals display a range of age-dependent phenotypes distinct from those previously reported in mouse models of amyotrophic lateral sclerosis Type 8. A loss of motor neurones in VapBP56S/+ and VapBP56S/P56S animals is indicated by a reduction in the number of large choline acetyl transferase–staining cells in the spinal cord. VapB−/− animals exhibit a relative increase in cytoplasmic TDP-43 levels compared with the nucleus, but no large protein aggregates. Concomitant with these spinal cord pathologies VapBP56S/+, VapBP56S/P56S and VapB−/− animals exhibit age-dependent changes in paw placement and exerted pressures when traversing a CatWalk apparatus, consistent with a somatosensory dysfunction. Extramotor dysfunction is reported in half the cases of motor neurone disease, and this is the first indication of an associated sensory dysfunction in a rodent model of amyotrophic lateral sclerosis. Different rodent models may offer complementary experimental platforms with which to understand the human disease.
Low-intensity pulsed ultrasound for ‘no-option’ chronic/critical limb-threatening ischaemia in a patient with Buerger disease: a case report
Authors: Mohamad Yusoff Farina , Kajikawa Masato , Sakamoto Takumi , Tanaka Akio , Higashi Yukihito 
Published: May 2024

Abstract

Background
Buerger disease, also known as Winiwarter–Buerger disease or thromboangiitis obliterans (TAO), is a non-specific inflammation of small- and medium-sized arteries with thrombus obliteration and without atherosclerotic changes. Patients with TAO can develop chronic limb-threatening ischaemia (CLTI) and are at risk of limb amputation despite smoking cessation and exercise therapy recommendations.

Case summary
A 72-year-old Japanese man presented with painful discolouration of toes and renal impairment. He was diagnosed with Rutherford classification Stage 6 CLTI with immunoglobulin A nephropathy. He refused limb amputation. Clinical symptoms reduced after treatment with low-intensity pulsed ultrasound (LIPUS). LIPUS is a non-invasive option to alleviate peripheral arterial disease symptoms. Despite the initiation of conventional therapy measures, there was a worsening of the limb condition. The non-invasive investigational treatment option of LIPUS was initiated after the poor clinical outcomes of the conventional therapy measures. The patient’s symptoms in the bilateral lower limbs, ulcers, and the blue-coloured toes gradually lessened. After 1 year of treatment with LIPUS, he had achieved better walking independence with improved quality of life.

Discussion
Low-intensity pulsed ultrasound is a non-invasive option for therapeutic angiogenesis with the potential to improve ischaemic limb conditions in patients with peripheral arterial disease and to avoid major amputation procedures.
Unmeasurable low vitamin D levels caused by a novel, homozygote loss-of-function variant in the group-specific component gene
Authors: Nygaard Rie Harboe , Lauritzen Esben Stistrup , Sikjær Tanja , Højskov Carsten Schriver , Rejnmark Lars , Møller Holger Jon 
Published: May 2024

Abstract
A 29-year-old female, born to consanguineous parents, was found with unmeasurable levels of vitamin D (&lt;10 nmol/L) after routine biochemical screening during her first pregnancy. She did not respond to either oral or intramuscular vitamin D supplementation and was an otherwise healthy young woman, with no signs of rickets, osteomalacia, osteoporosis, or secondary hyperparathyroidism. Western blot analysis revealed total lack of vitamin D binding protein, and next generation sequencing confirmed a novel, pathogenic homozygote loss-of-function mutation in exon 13 of the group-specific component gene, that encodes the poly A tail for vitamin D binding protein. She was therefore diagnosed with hereditary DBP deficiency, and vitamin D supplementation was diminished to life-long regular vitamin D supplementation (25 μg per day). This case is extremely interesting, as it expands our knowledge of vitamin D physiology and supports the free hormone hypothesis, given that the patient was asymptomatic despite no measurable levels of vitamin D.
Stochastic time series analysis of atrial fibrillatory electrograms in paroxysmal atrial fibrillation
Authors: Leftheriotis D , Giannakakis G , Flevari P , Adamopoulos A , Fiippatos G 
Published: May 2024

Abstract

Background/Introduction
Regional dominant frequency and instantaneous frequency modulation of short fractionated atrial electrograms have been associated with ablation targets and the prognosis of atrial fibrillation (AF). However, inconsistent and not fully comprehensible results have been reported.

Purpose
To construct a simple computational algorithm for the analysis of continuous fibrillatory atrial electrograms and evaluate it in clinical practice, among patients with paroxysmal AF.

Methods
Before the first cryo-balloon ablation, 3-minute continuous local electrogram recordings during pace-induced AF were obtained by the circumferential catheter from the left atrial appendage (LAA) and each pulmonary vein: left superior (LSPV), left inferior (LIPV), right superior (RSPV) and right inferior (RIPV). Following time- and frequency-domain analysis, non-linear detrended fluctuation analysis (DFA α) with analysis for short-term (DFA α1) and long-term fluctuations (DFA α2) was performed. The signals were detrended by subtracting time series polynomial fit and badpass filtered in the MATLAB environment (cut-off voltage 0.1 mV to avoid scar and artifacts).

Results
Fifteen patients were studied. Among different atrial areas, higher mean peak rate (pr) along with lower standard deviation of between peaks intervals (sdpp) and root square of peak-to-peak differences (rmppd) were observed in the LAA and left veins (Fig. 1). In patients with longer AF history (&gt; 2 yrs), lower α, α1 and α2 exponents of DFA were observed (Fig. 2).

Conclusions
This algorithm depicted dissimilar impact on atrial electrical activity between different atrial areas. Patients with longer AF history had less self-similarity in local LAA electrograms. This might indicate possible ablation targets and reveal patients with greater AF burden and worse arrhythmic prognosis.Leftheriotis - Figure 1Leftheriotis - Figure 2
Impact of induced atrial fibrillation during atrioventricular nodal reentrant tachycardia ablation
Authors: Santos A R , Ferreira A , Lousinha A , Cruz M , Portugal G , Osorio P , Valente B , Cunha P , Paulo M , Bras M , Delgado A S , Guerra C , Fonseca H , Oliveira M , Ferreira R 
Published: May 2024

Abstract

Ablation is the treatment of choice for atrioventricular nodal reentrant tachycardia (AV NRT). Atrial fibrillation (AF) can incidentally occur during this procedure, labeling these patients (P) as susceptible for AF in the future. Our aim was to assess the presence of new onset AF in P who presented this arrhythmia during the electrophysiological study (EPS).

Methods
We retrospectively analyzed 580 P that underwent AV NRT ablation between November 2008 and August 2020. Patients with previous AF were excluded. After having AF induced during the EPS, 62 P were identified as susceptible for developing AF. Data were collected by contacting P and consulting medical records.

Results
The studied population had 64.5% (n=40) females, 35.5% (n=22) males, with ages between 15 and 81years old (median 52.3, mean 50.1). At ablation date, 33.9% (n=21) had hypertension, 3.2% (n=2) diabetes, 6.5% (n=4) chronic kidney disease, 3.2% (n=2) obstructive sleep apnea, 6.5% (n=4) coronary artery disease and 6.5% (n=4) structural heart disease. Previously to ablation, 46.8% (n=29) were on beta-blocker, 1.6% (n=1) on amiodarone and 3.2% (n=2) on flecainide. When admitted to the procedure, 98.4% (n=61) were in sinus rhythm and 1.6% (n=1) had a pacemaker. "Slow-fast" was the most common AVNRT type (96.8%). During the EPS, other arrhythmias were induced: in 12.9% (n=8) atrial flutter and in 9.7% (n=6) atrial tachycardia. After AF induction, 12.9% (n=8) needed electrical cardioversion and 3.2% (n=2) needed both electrical and pharmacological. At the time of ablation, transient complete atrioventricular block was noted in 6.5% (n=4) P. When contacted, 100% (n=62) had 1 year of follow-up, 69.4% (n=43) 5 years and 25.8% (n=16) 10 years, with a mean follow-up of 6.6 years. It was not possible to contact 12.9% (n=8) of the P, of those, 6.5% (n=4) died and 6.5% (n=4) did not reply. Recurrence of AV NRT was documented in 6.4% (n=4) P and all underwent a successful second ablation. Almost one third, 32.3% (n=20), were symptomatic, mainly with palpitations, and 27.4% (n=17) maintained follow up with a Cardiologist. New-onset AF was documented in 1 P only (1.6%), diagnosed 9 years after the procedure.

Conclusion
In our cohort, the induction of AF during EPS did not translate into clinical AF during follow-up. Whether this is a nonspecific finding related to catheter manipulation or pacing maneuvers on pharmacological provocation deserves further investigation.
Atrial high-rate episodes detected by cardiac implantable electronic devices: arrhythmic burden and progression towards de-novo clinical atrial fibrillation
Authors: Imberti J F , Tosetti A , Mei D A , Gerra L , Golle' A , Martella A , Bonini N , Mauro E , Turco V , Casali E , Vitolo M , Boriani G 
Published: May 2024

Abstract

Background
Atrial high rate episodes (AHRE) detected by cardiac implantable electronic devices (CIEDs) are associated with a higher risk of thromboembolic events, but whether oral anticoagulants (OACs) improve patient outcomes is still debated. On the other hand, OACs benefits in patients with clinical atrial fibrillation (AF) are well established. Therefore, the potential progression of AHRE towards clinical AF should be promptly recognized.

Purpose
To evaluate the incidence of de-novo clinical AF and its potential predictors.

Methods
Consecutive CIED patients presenting AHRE (with confirmation of an arrhythmia lasting 5 min–23 h 59 min, atrial rate 175/min, with no AF at 12-lead ECG and no prior clinical AF) were retrospectively enrolled. Potential predictors of incident clinical AF were investigated by building six different multivariable Cox’s regression analyses, and the duration of the single longest AHRE episode during follow-up was used as a time-dependent covariate.

Results
126 patients (median age 79.7 (73.8-84.6), 34.1% female) had available follow-up data. Detailed patients' characteristics are provided in Figure 1. Over a median follow-up of 1128 (580-1646) days, 41/126 (32.5%) patients developed incident clinical AF. A single longest AHRE episode lasting ≥ 6 hours (h) was found associated with a higher risk of incident clinical AF after adjusting for HATCH score, female sex, and coronary artery disease (CAD) (Hazard ratio (HR) 2.82; 95%CI 1.32-6.04) and also in the model adjusting for CHA2DS2-VASc score and CKD (HR 3.13; 95%CI 11.57-6.25). Similar results were found for a single longest AHRE episode lasting ≥ 12 hours (HR 4.91; 95%CI 2.31-10.42 and HR 4.90; 95%CI 2.50-9.60, respectively), and lasting ≥ 24h (HR 4.40; 95%CI 1.82-10.60 and HR 4.56; 95%CI 2.05-10.14, respectively) (Figure 2). On the other hand, HATCH score and CHA2DS2-VASc score were independently associated with a higher risk of incident clinical AF only in multivariable models adjusting for episodes of AHRE lasting ≥6 h (HR 1.42; 95%CI 1.02-1.97 and HR 1.37; 95%CI 1.03-1.83, respectively) but this association was not confirmed after adjusting for AHRE of longer duration.

Conclusions
In patients with AHRE, the incidence of de-novo clinical AF is high in a three-year follow-up. Baseline patients’ characteristics (HATCH and CHA2DS2-VASc scores) and AHRE duration during follow-up may help to intensify monitoring and decision-making, being independently associated with incident clinical AF at follow-up.Baseline characteristicsMultivariate Cox's regression analysis