bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced upregulation of SIRT1 via pioglitazone and ligustrazine confers protection against ethanol-induced gastric ulcer in rats
Authors: Mahmoud Sara A. , Elkhoely Abeer , El-Sayed Elsayed K. , Ahmed Amany A. E. 
Published: March 2024

AbstractGastric ulcer is a disturbing disease that impacts many people worldwide. Pioglitazone (Piog), a thiazolidinedione, and ligustrazine (Ligu), a natural component of Ligusticum chuanxiong possess gastroprotective properties. However, the underlying mechanism is not well elucidated. The present study aimed to investigate the gastroprotective effects of Piog (15 mg/kg, p.o.), Ligu (15 mg/kg, p.o.), and their combination against ethanol-induced gastric ulcer in rats. Omeprazole (10 mg/kg) was used as a standard. Pre-treatment for 7 days with Piog, Ligu, and (Piog+Ligu) effectively alleviated ethanol-predisposed oxidative stress and inflammation through restoring HO-1, GSH, and SOD tissue levels and decreasing elevated MDA, TNF-α, ICAM, I-NOS, and IL-1β contents. Moreover, Piog, Ligu, and (Piog+Ligu) markedly inhibited the ethanol-induced increase of gastric NF-KB and BAX. In contrast, this pre-treatment regimen significantly accelerated protein expression of SIRT1, Nrf2, and Bcl-2, along with autophagic proteins, ATG5 and Beclin. Interestingly, macroscopic, histopathological examination and mucin content were in harmony with previous results, where pre-treatment with Piog, Ligu, and (Piog+Ligu) showed a declined mucosal injury as evidenced by the remarkable decrease of the ulcer area percentage by 62.3%, 38.7%, and 91.2%, respectively, compared to the ethanol-ulcerated group. In conclusion, Piog and Ligu exhibited remarkable gastroprotective properties. Our study was the first to show that Piog, Ligu, and (Piog+Ligu) ameliorated oxidative stress, inflammation, and apoptosis and accelerated the autophagic process via the upregulation of the upstream SIRT1 protein. It is worth mentioning that future studies are needed to pave the way for the clinical use of Piog and Ligu as gastro-protective agents.
Deoxygenation following coral spawning and low-level thermal stress trigger mass coral mortality at Coral Bay, Ningaloo Reef
Authors: Richards Zoe T. , Haines Lewis , Ross Claire , Preston Sophie , Matthews Troy , Terriaca Anthony , Black Ethan , Lewis Yvette , Mannolini Josh , Dean Patrick , Middleton Vincent , Saunders Ben 
Published: March 2024

AbstractOxygen depletion is well recognized for its role in the degradation of tropical coral reefs. Extreme acute hypoxic events that lead to localized mass mortality and the formation of ‘dead zones’ (a region where few or no organisms can survive due to a lack of oxygen) are particularly concerning as they can result in wide-ranging losses of biodiversity, ecosystem productivity and functioning, economic prosperity, and wellbeing. In March of 2022, the annual coral spawning event at Bills Bay (Coral Bay, Ningaloo Reef, Western Australia) coincided with elevated seawater temperature, calm weather conditions and a flood tide resulting in coral spawn becoming trapped in Bills Bay. Immediately after, there was a mass fish kill, which is believed to have been caused by local eutrophication resulting in severe oxygen depletion. The impact the deoxygenation and thermal stress event had on benthic communities has not yet been quantified; hence, the principal aim of this study is to document the extent of change that occurred in the benthic communities before and after the 2022 coral spawning event over a spatial gradient from the nearshore to mid-reef. Percent coral cover in the Bay decreased from 55.62 ± 2.26% in 2016–2018 and 70.44 ± 5.24% in 2021 to 1.16 ± 0.51% in 2022. Over the same period, the percent cover of turf algae increased from 27.40 ± 2.00% in 2016–2018 and 24.66 ± 6.67% in 2021 to 78.80 ± 3.06% in 2022, indicating a dramatic phase shift occurred at Bills Bay. The abundance of healthy coral colonies recorded on replicated belt transects at nine sites declined from 3452 healthy individuals in 2018 to 153 individuals in 2022 and coral generic richness decreased by 84.61%, dropping from 26 genera in 2018 to 4 genera in 2022. Previously dominant genera such as Acropora,Montipora and Echinopora, were extirpated from survey sites. Isolated colonies of massive Porites spp. and encrusting Cyphastrea sp. survived the event and understanding the mechanisms underpinning their greater survivorship is an important area of future research. Long-term monitoring is recommended to track the community recovery process and improve our understanding of the longer-term implications of this acute mortality event on the ecological, socio-economic and cultural values of Ningaloo Reef.
Innervation pattern of the unclosed detrusor muscle in classic bladder exstrophy: a study of patients with urothelial overexpression of nerve growth factor
Authors: Promm Martin , Otto Wolfgang , Götz Stefanie , Burger Maximilian , Müller Karolina , Rubenwolf Peter , Neuhuber Winfried L. , Rösch Wolfgang H. 
Published: March 2024

Abstract
Purpose
An overexpression of nerve growth factor (NGF) in the urothelium is discussed to lead to neuronal hyperinnervation of the bladder detrusor. The aim was to assess the sensory and sympathetic innervation of the detrusor in unclosed exstrophic bladders patients with known overexpression of NGF in the urothelium.

Methods
Full-thickness bladder biopsies were prospectively obtained from 34 infants at delayed primary bladder closure between 01/2015 and 04/2020. The bladder biopsies were immunohistochemically stained with antibodies against S100, calcitonin gene-related peptide (anti-CGRP), Neurofilament 200 (anti-NF200), and tyrosine-hydroxylase (anti-TH). Specimens from 6 children with congenital vesicoureterorenal reflux (VUR) served as controls.

Results
There was no statistically significant difference in nerve fiber density in any of the immunohistochemical assessments (anti-S100 [p = 0.210], anti-CGRP [p = 0.897], anti-NF200 [p = 0.897]), and anti-TH [p = 0.956]) between patients with BE and patients with VUR. However, we observed a trend toward lower nerve fiber densities in exstrophic detrusor.

Conclusion
Overall our results showed an unharmed innervation pattern in this cohort but a lower density of nerve fibers in the detrusor compared to controls. Further studies in patients after successful primary closure are needed to clarify the potential impact of the urothelial overexpression of NGF modulating the innervation pattern in exstrophic bladders.
Lupusnephritis und assoziierte thrombotische Mikroangiopathie
Authors: Schuster Antonia , Banas Bernhard , Bergler Tobias 
Published: March 2024

ZusammenfassungDie Lupusnephritis stellt die häufigste Manifestation eines systemischen Lupus an den soliden Organen dar und geht mit einem erhöhten Risiko für eine chronische Niereninsuffizienz einher. Das gleichzeitige Auftreten einer Lupusnephritis mit einer thrombotischen Mikroangiopathie wird als selten beschrieben, impliziert jedoch das Risiko fataler Organdysfunktionen. Wir berichten von drei Patienten, bei denen diese beiden Krankheitsentitäten parallel auftraten und eine intensivierte immunsuppressive Therapie auch mittels Komplementblockade notwendig machten.
RNA aptamer reveals nuclear TDP-43 pathology is an early aggregation event that coincides with STMN-2 cryptic splicing and precedes clinical manifestation in ALS
Authors: Spence Holly , Waldron Fergal M. , Saleeb Rebecca S. , Brown Anna-Leigh , Rifai Olivia M. , Gilodi Martina , Read Fiona , Roberts Kristine , Milne Gillian , Wilkinson Debbie , O’Shaughnessy Judi , Pastore Annalisa , Fratta Pietro , Shneider Neil , Tartaglia Gian Gaetano , Zacco Elsa , Horrocks Mathew H. , Gregory Jenna M. 
Published: March 2024

AbstractTDP-43 is an aggregation-prone protein which accumulates in the hallmark pathological inclusions of amyotrophic lateral sclerosis (ALS). However, the analysis of deeply phenotyped human post-mortem samples has shown that TDP-43 aggregation, revealed by standard antibody methods, correlates poorly with symptom manifestation. Recent identification of cryptic-splicing events, such as the detection of Stathmin-2 (STMN-2) cryptic exons, are providing evidence implicating TDP-43 loss-of-function as a potential driving pathomechanism but the temporal nature of TDP-43 loss and its relation to the disease process and clinical phenotype is not known. To address these outstanding questions, we used a novel RNA aptamer, TDP-43APT, to detect TDP-43 pathology and used single molecule in situ hybridization to sensitively reveal TDP-43 loss-of-function and applied these in a deeply phenotyped human post-mortem tissue cohort. We demonstrate that TDP-43APT identifies pathological TDP-43, detecting aggregation events that cannot be detected by classical antibody stains. We show that nuclear TDP-43 pathology is an early event, occurring prior to cytoplasmic accumulation and is associated with loss-of-function measured by coincident STMN-2 cryptic splicing pathology. Crucially, we show that these pathological features of TDP-43 loss-of-function precede the clinical inflection point and are not required for region specific clinical manifestation. Furthermore, we demonstrate that gain-of-function in the form of extensive cytoplasmic accumulation, but not loss-of-function, is the primary molecular correlate of clinical manifestation. Taken together, our findings demonstrate implications for early diagnostics as the presence of STMN-2 cryptic exons and early TDP-43 aggregation events could be detected prior to symptom onset, holding promise for early intervention in ALS.
Modelling ancient magma plumbing systems through clinopyroxene populations: a case study from Middle Triassic volcanics (Dolomites, Italy)
Authors: Nardini Nicolò , Casetta Federico , Petrone Chiara Maria , Buret Yannick , Ntaflos Theodoros , Coltorti Massimo 
Published: March 2024

AbstractModelling plumbing systems dynamics of active volcanoes through textural and chemical studies of mineral phases is crucial to unravel their eruptive behaviour, but it is rarely applied in ancient volcanic and volcano-plutonic systems. Here, we present an investigation of the architecture, magma dynamics and pre-eruptive timing of Middle Triassic plumbing systems in the Dolomites area (Southern Alps) through a detailed investigation of textures and compositional zoning of clinopyroxenes in lavas and dykes from Predazzo, Mt. Monzoni, Cima Pape and Sciliar volcano-plutonic complexes. The clinopyroxene composition varies between low-Mg# (67–78), low-Cr augite and high-Mg# (77–91), Cr-rich diopside. Diopside is less frequent and appears as variably thick single or multiple bands between augitic cores and rims or as resorbed homogeneous, or patchy-zoned and mottled cores. Rims are homogeneous or oscillatory zoned, with augitic composition. The mid- to low-crustal plumbing systems of all volcanic centres were characterised by the presence of a mildly evolved trachyandesitic magma (Mg# 45; T = 1044–1118 °C), where augitic clinopyroxene formed. Periodic mafic injections of more primitive and hotter trachybasaltic magma (Mg# 56; T = 1056–1170 °C) caused frequent crystallisation of diopsidic bands around augitic cores. The presence of resorbed or patchy-zoned mottled diopsidic cores in clinopyroxene phenocrysts, as well as of rare clinopyroxenitic xenoliths with analogous diopsidic composition, indicates the recycling and remobilisation of antecrysts from the deeper part of the plumbing system, which was probably located at a depth of 10–17 km. Diffusion chronometry models based on Fe–Mg interdiffusion in clinopyroxene revealed that the time elapsed from the mafic injection into the shallow portion of the plumbing systems to the eruption ranges from decades to < 1 year. Our findings enabled us to resolve the different plumbing system dynamics acting at the local scale beneath each volcanic centre. Our data indicate a striking similarity with magma dynamics and timing of pre-eruptive processes at active volcanoes: therefore, we posit that this work sets a starting point to deepen our knowledge of the volcano-plutonic links and, in turn improves our ability to interpret the main processes acting in active plumbing systems.
Visual and vestibular motion perception in persistent postural-perceptual dizziness (PPPD)
Authors: Storm Renana , Krause Janina , Blüm Smila-Karlotta , Wrobel Viktoria , Frings Antonia , Helmchen Christoph , Sprenger Andreas 
Published: March 2024

AbstractPersistent postural-perceptual dizziness (PPPD) is a chronic disorder of perceived unsteadiness. Symptoms can be exacerbated in visually complex stationary or moving environment. Visual dependence and increased motion sensitivity are predictors for PPPD but its pathophysiology remains unknown. We hypothesized an abnormal sensory–perceptual scaling mechanism in PPPD and tested visual- and vestibular perceptional thresholds in 32 patients and 28 age-matched healthy control subjects (HC). All participants showed normal vestibular function tests on quantitative testing. Visual motion coherence thresholds were assessed by random dot kinetomatograms. Vestibular perceptional thresholds of egomotion were assessed by binaural galvanic vestibular stimulation (GVS) and passive chair rotation around an earth-vertical axis. Chair rotation trials were contrasted with no-motion (sham) stimulus trials. Mean thresholds of visual motion perception were higher in patients compared to HC. The perception threshold of GVS was lower in patients but the threshold of correctly perceived egomotion during chair rotation did not differ. Interestingly, the number of trials with correct perception in the no-motion condition increased with the threshold of correct responses for rotatory egomotion in patients. Unlike expected, PPPD patients required more coherently moving random dots than HC to perceive visual motion. A poorer complex visual motion recognition, e.g., traffic visual stimuli, may increase anxiety and levels of uncertainty as visuomotor reactions might occur delayed. The vestibular rotatory perception threshold predicted the probability of making false assignments in the sham condition in PPPD, i.e., patients who readily recognize the correct egomotion direction are prone to perceive egomotion in the no-motion condition. As this relation was not found in healthy subjects, it may reflect an abnormal sensory–perceptual scaling feature of PPPD.
Supra- and infra-tentorial degeneration patterns in primary lateral sclerosis: a multimodal longitudinal neuroradiology study
Authors: Kleinerova Jana , Tahedl Marlene , Tan Ee Ling , Delaney Siobhan , Hengeveld Jennifer C. , Doherty Mark A. , McLaughlin Russell L. , Hardiman Orla , Chang Kai Ming , Finegan Eoin , Bede Peter 
Published: March 2024

Abstract
Background
Primary lateral sclerosis (PLS) is traditionally solely associated with progressive upper motor neuron dysfunction manifesting in limb spasticity, gait impairment, bulbar symptoms and pseudobulbar affect. Recent studies have described frontotemporal dysfunction in some patients resulting in cognitive manifestations. Cerebellar pathology is much less well characterised despite sporadic reports of cerebellar disease.

Methods
A multi-timepoint, longitudinal neuroimaging study was conducted to characterise the evolution of both intra-cerebellar disease burden and cerebro-cerebellar connectivity. The volumes of deep cerebellar nuclei, cerebellar cortical volumes, cerebro-cerebellar structural and functional connectivity were assessed longitudinally in a cohort of 43 individuals with PLS.

Results
Cerebello-frontal, -temporal, -parietal, -occipital and cerebello-thalamic structural disconnection was detected at baseline based on radial diffusivity (RD) and cerebello-frontal decoupling was also evident based on fractional anisotropy (FA) alterations. Functional connectivity changes were also detected in cerebello-frontal, parietal and occipital projections. Volume reductions were identified in the vermis, anterior lobe, posterior lobe, and crura. Among the deep cerebellar nuclei, the dorsal dentate was atrophic. Longitudinal follow-up did not capture statistically significant progressive changes. Significant primary motor cortex atrophy and inter-hemispheric transcallosal degeneration were also captured.

Conclusions
PLS is not only associated with upper motor neuron dysfunction, but cerebellar cortical volume loss and deep cerebellar nuclear atrophy can also be readily detected. In addition to intra-cerebellar disease burden, cerebro-cerebellar connectivity alterations also take place. Our data add to the evolving evidence of widespread neurodegeneration in PLS beyond the primary motor regions. Cerebellar dysfunction in PLS is likely to exacerbate bulbar, gait and dexterity impairment and contribute to pseudobulbar affect.
CHD8-related disorders redefined: an expanding spectrum of dystonic phenotypes
Authors: Sorrentino Ugo , Boesch Sylvia , Doummar Diane , Ravelli Claudia , Serranova Tereza , Indelicato Elisabetta , Winkelmann Juliane , Burglen Lydie , Jech Robert , Zech Michael 
Published: March 2024

Abstract
Background
Heterozygous loss-of-function variants in CHD8 have been associated with a syndromic neurodevelopmental-disease spectrum, collectively referred to as CHD8-related neurodevelopmental disorders. Several different clinical manifestations, affecting neurodevelopmental and systemic domains, have been described, presenting with highly variable expressivity. Some expressions are well established and comprise autism spectrum disorders, psychomotor delay with cognitive impairment, postnatal overgrowth with macrocephaly, structural brain abnormalities, gastrointestinal disturbances, and behavioral and sleep-pattern problems. However, the complete phenotypic spectrum of CHD8-related disorders is still undefined. In 2021, our group described two singular female patients with CHD8-related neurodevelopmental disorder and striking dystonic manifestations, prompting the suggestion that dystonia should be considered a possible component of this condition.

Case series presentation
We describe three additional unrelated female individuals, each carrying a different CHD8 frameshift variant and whose clinical presentations were primarily characterized by young-onset dystonia. Their dystonic manifestations were remarkably heterogeneous and ranged from focal, exercise-dependent, apparently isolated forms to generalized permanent phenotypes accompanied by spasticity and tremor. Neurocognitive impairment and autistic behaviors, typical of CHD8-related disorders, were virtually absent or at the mild end of the spectrum.

Conclusions
This work validates our previous observation that dystonia is part of the phenotypic spectrum of CHD8-related neurodevelopmental disorders with potential female preponderance, raising new challenges and opportunities in the diagnosis and management of this condition. It also highlights the importance of in-depth neurologic phenotyping of patients carrying variants associated with neurodevelopmental disorders, as the connection between neurodevelopmental and movement disorders is proving closer than previously appreciated.
Cortical and spinal responses to short-term strength training and detraining in young and older adults in rectus femoris muscle
Authors: Gomez-Guerrero Gonzalo , Avela Janne , Jussila Ilkka , Pihlajamäki Esa , Deng Fu-Yu , Kidgell Dawson J. , Ahtiainen Juha P. , Walker Simon 
Published: March 2024

Abstract
Introduction
Strength training mitigates the age-related decline in strength and muscle activation but limited evidence exists on specific motor pathway adaptations.

Methods
Eleven young (22–34 years) and ten older (66–80 years) adults underwent five testing sessions where lumbar-evoked potentials (LEPs) and motor-evoked potentials (MEPs) were measured during 20 and 60% of maximum voluntary contraction (MVC). Ten stimulations, randomly delivered, targeted 25% of maximum compound action potential for LEPs and 120, 140, and 160% of active motor threshold (aMT) for MEPs. The 7-week whole-body resistance training intervention included five exercises, e.g., knee extension (5 sets) and leg press (3 sets), performed twice weekly and was followed by 4 weeks of detraining.

Results
Young had higher MVC (~ 63 N·m, p = 0.006), 1-RM (~ 50 kg, p = 0.002), and lower aMT (~ 9%, p = 0.030) than older adults at baseline. Young increased 1-RM (+ 18 kg, p < 0.001), skeletal muscle mass (SMM) (+ 0.9 kg, p = 0.009), and LEP amplitude (+ 0.174, p < 0.001) during 20% MVC. Older adults increased MVC (+ 13 N·m, p = 0.014), however, they experienced decreased LEP amplitude (− 0.241, p < 0.001) during 20% MVC and MEP amplitude reductions at 120% (− 0.157, p = 0.034), 140% (− 0.196, p = 0.026), and 160% (− 0.210, p = 0.006) aMT during 60% MVC trials. After detraining, young and older adults decreased 1-RM, while young adults decreased SMM.

Conclusion
Higher aMT and MEP amplitude in older adults were concomitant with lower baseline strength. Training increased strength in both groups, but divergent modifications in cortico-spinal activity occurred. Results suggest that the primary locus of adaptation occurs at the spinal level.
Identifying the most accurate machine learning classification technique to detect network threats
Authors: Farouk Mohamed , Sakr Rasha Hassan , Hikal Noha 
Published: March 2024

AbstractInsider threats have recently become one of the most urgent cybersecurity challenges facing numerous businesses, such as public infrastructure companies, major federal agencies, and state and local governments. Our purpose is to find the most accurate machine learning (ML) model to detect insider attacks. In the realm of machine learning, the most convenient classifier is usually selected after further evaluation trials of candidate models which can cause unseen data (test data set) to leak into models and create bias. Accordingly, overfitting occurs because of frequent training of models and tuning hyperparameters; the models perform well on the training set while failing to generalize effectively to unseen data. The validation data set and hyperparameter tuning are utilized in this study to prevent the issues mentioned above and to choose the best model from our candidate models. Furthermore, our approach guarantees that the selected model does not memorize data of the threats occurring in the local area network (LAN) through the usage of the NSL-KDD data set. The following results are gathered and analyzed: support vector machine (SVM), decision tree (DT), logistic regression (LR), adaptive boost (AdaBoost), gradient boosting (GB), random forests (RFs), and extremely randomized trees (ERTs). After analyzing the findings, we conclude that the AdaBoost model is the most accurate, with a DoS of 99%, a probe of 99%, access of 96%, and privilege of 97%, as well as an AUC of 0.992 for DoS, 0.986 for probe, 0.952 for access, and 0.954 for privilege.