bluuebunny/crossref_metadata_2025 huggingface dataset:
Once or consecutive administration of inhaled salbutamol in children with acute asthma exacerbation: Is an additional dose beneficial?
Authors: Özdemir Ali , Ersoy Murat , Aydoğdu Ayşe Kirmizitaş
Published: July 2024

Background

Although international guidelines generally recommend the back to back use of short‐acting β‐agonists (SABA) within a short time in the management of acute wheezing in children with asthma, there is still uncertainty in the evidence of short term outcome. Thus, this study aimed to investigate the efficacy of back to back and single use of inhaled SABA by lung function testing.

Methods

This was a prospective, double‐blinded, placebo controlled study conducted in children ≥6 years of age with a history of asthma. Children who presented with an acute asthma exacerbation (AAE) with a forced expiratory volume in 1 s (FEV1) between 40% to 60% were enrolled in the study if they had a first dose to SABA response of FEV1 ≥ 12%. All children were then randomly assigned either to receive two additional doses of inhaled SABA (300 µg per dose) or placebo. Spirometric analysis included forced vital capacity (FVC), FEV1, FEV1/FVC, PEF, and FEF25−75 at baseline, 15, 30, and 45 min for each group. Oxygen saturation and heart rate were monitored during the study period.

Results

A total of 93 patients (inhaled SABA group; n = 48 vs. placebo group; n = 45) out of 110 enrolled patients completed the study. Baseline demographic characteristics of patients include age, gender, age of diagnosis, parental asthma, history of allergic rhinitis and atopic dermatitis, current asthma treatment, IgE and skin prick test were similar among groups. (p > .05) When lung function parameters were compared at each time interval during the study period, there were no statistical significance found in FVC, FEV1, FEV1/FVC, PEF and forced expiratory flow between 25% and 75% (FEF25−75) among groups. (p > .05) There were also no differences between groups for changes in heart rate and oxygen saturation. (p > .05)

Conclusion

A single dose of inhaled SABA provides similar short term bronchodilator effect as back to back administration of inhaled SABA in children with AAE who showed an initial response to SABA of FEV1 ≥ 12%.
Concentration Dependence Orange Light Generation Through Sm3+‐Doped Soda Lime Alumino Borate Glasses for Orange Laser Medium Material
Authors: Jarucha Nawarut , Ruangtaweep Yotsakit , Meejitpaisan Piyachat , Kim Hong Joo , Boontueng Phongnared , Kobdaj Chinorat , Ritjoho Narongrit , Sanghangthum Taweap , Valiev Damir , Kaewkhao Jakrapong
Published: July 2024

The melt‐quenching technique is used to fabricate calcium sodium aluminum borate glasses (Sm: ANCB) doped with varying concentrations of Sm3+ ions. Characteristics of ANCBSm glasses, including density, molar volume, refractive index, absorption, emission (via visible light, X‐ray, and proton excitation), decay time, and CIE color coordinates, are analyzed. The density, molar volume, and refractive index of ANCBSm glass increased with Sm2O3 concentration. Sm3+ ions enabled photon absorption in both visible and NIR regions, with a strong reddish‐orange emission at 600 nm due to the 6H5/2 → 6P3/2 transition under various excitations. X‐ray excitation is also compared with BGO scintillation crystals. The J–O theory predicted the radiative properties of Sm3+ ion emission levels. Decay curves of the 6H5/2 levels showed a single exponential nature with a millisecond‐order lifetime. CIE chromaticity of ANCBSm glasses is in the reddish‐orange region. ANCBSm glasses have potential applications in orange laser medium material.
A novel therapy for spontaneous previable amniotic fluid leak by using intra‐amniotic platelet rich fibrin and plasma: A case report
Authors: Rajashekar Sowmya H. , S. J. Seema , H. K. Swathi , Mishra Prabhu C. , Somaiya Praveen N. , Rao Yogitha M.
Published: July 2024

Introduction

Previable premature rupture of membrane (PV‐PROM) is a complex clinical situation posing considerable risks to the foetus. There is an extreme paucity of management options and clear guidelines in the literature for this dismal situation. This is the first report on usage of a novel combination of cellular therapeutic agents in a case of PROM. This study reports the earliest gestational age at which a case of spontaneous PV‐PROM (sPV‐PROM) has been successfully dealt by active management and, the longest period of continuation of pregnancy in a singleton sPV‐PROM for a total of 149 days.

Objective

To study the benefit of Intraamniotic Injection of PRF and PRP (IFPRP) in an index case of PV‐PROM.

Design

This is a case report of a 26‐year‐old woman with a recurrent, sPV‐PROM at 14 weeks 2 days with a previous pregnancy loss due to PV‐PROM at 18 weeks managed in a private reproductive health hospital in Mysore, India.

Methods

Our subject underwent an elective cervical stitch at 14 weeks. She had confirmed, repeated episodes of leak after 30 h of the procedure. Apart from aggressive management to control infection with vaginal asepsis, an Intraamniotic injection of 9 mL of autologous PRF and 4.5 mL of PRP was done under ultrasound guidance. The pregnancy was monitored closely for signs of infection and foetal wellbeing.

Results

The amniotic fluid leak stopped immediately after IFPRP for 36 h. After two more bouts of small leak, it stopped completely. She delivered a healthy baby of 3.4 kg at 35 weeks 4 days. The mother and baby did well postnatally.

Conclusion

Our protocol for fixing the leak is simple, easy to use, and can be done in resource‐poor settings which we consider is a big advantage. Further studies are needed to explore its potential in treating PROM.
Determining sample size in a personalized randomized controlled (PRACTical) trial
Authors: Turner Rebecca M. , Lee Kim May , Walker A. Sarah , Ellis Sally , Sharland Michael , Bielicki Julia A. , Stöhr Wolfgang , White Ian R.
Published: July 2024

In clinical settings with no commonly accepted standard‐of‐care, multiple treatment regimens are potentially useful, but some treatments may not be appropriate for some patients. A personalized randomized controlled trial (PRACTical) design has been proposed for this setting. For a network of treatments, each patient is randomized only among treatments which are appropriate for them. The aim is to produce treatment rankings that can inform clinical decisions about treatment choices for individual patients. Here we propose methods for determining sample size in a PRACTical design, since standard power‐based methods are not applicable. We derive a sample size by evaluating information gained from trials of varying sizes. For a binary outcome, we quantify how many adverse outcomes would be prevented by choosing the top‐ranked treatment for each patient based on trial results rather than choosing a random treatment from the appropriate personalized randomization list. In simulations, we evaluate three performance measures: mean reduction in adverse outcomes using sample information, proportion of simulated patients for whom the top‐ranked treatment performed as well or almost as well as the best appropriate treatment, and proportion of simulated trials in which the top‐ranked treatment performed better than a randomly chosen treatment. We apply the methods to a trial evaluating eight different combination antibiotic regimens for neonatal sepsis (NeoSep1), in which a PRACTical design addresses varying patterns of antibiotic choice based on disease characteristics and resistance. Our proposed approach produces results that are more relevant to complex decision making by clinicians and policy makers.
Recent Innovations and Technical Advances in High‐Throughput Parallel Single‐Cell Whole‐Genome Sequencing Methods
Authors: Qiao Yi , Cheng Tianguang , Miao Zikun , Cui Yue , Tu Jing
Published: July 2024

Single‐cell whole‐genome sequencing (scWGS) detects cell heterogeneity at the aspect of genomic variations, which are inheritable and play an important role in life processes such as aging and cancer progression. The recent explosive development of high‐throughput single‐cell sequencing methods has enabled high‐performance heterogeneity detection through a vast number of novel strategies. Despite the limitation on total cost, technical advances in high‐throughput single‐cell whole‐genome sequencing methods are made for higher genome coverage, parallel throughput, and level of integration. This review highlights the technical advancements in high‐throughput scWGS in the aspects of strategies design, data efficiency, parallel handling platforms, and their applications on human genome. The experimental innovations, remaining challenges, and perspectives are summarized and discussed.
A sharper bound of the Hotelling–Solomons inequality
Authors: Maruyama Yuzo
Published: July 2024

The original Hotelling–Solomons inequality states that an upper bound of the absolute difference between the mean and median, standardised by the standard deviation, is 1. However, in this paper, we introduce a new bound that depends on the sample size, which is strictly smaller than 1.
Myxoid leiomyosarcoma of the oviduct and uterus in a Cockatiel (Nymphicus hollandicus)
Authors: Golchin Diba , Borhanikiya Ali
Published: July 2024

An 11‐year‐old female cinnamon cockatiel (Nymphicus hollandicus) was presented with a coelomic distention. Dystocia was suspected, given its previous history of a calcium‐deficient diet and multiple instances of nonobstructive dystocia. Exploratory coeliotomy revealed a large intraluminal mass extending through the magnum to the uterus (shell gland). Metastasis and multiorgan involvement were not seen. Histopathologically, malignant and invasive fascicles of spindle cells were associated with abundant myxoid matrix and hypocellular areas. Multinucleation, bizarre cells and atypical mitotic figures were prominent. Masson's trichrome staining verified the muscular origin, and the myxoid matrix was demonstrated utilizing Alcian blue. The neoplastic cells exhibited alpha‐smooth muscle actin and desmin immunoreactivity and were negative for vimentin. Thus, the patient was diagnosed with oviductal and uterine myxoid leiomyosarcoma (LMS). The patient survived 34 days post‐surgery before death associated with suspected enteritis. Myxoid LMS is an extremely rare neoplasm in animals. To our knowledge, myxoid LMS has not been reported previously in pet birds.
UoC‐11: An Interpenetrating MOF from Fluorinated BTB Ligands and a 1‐D Mg Based SBU
Authors: Sebastian Sean S. , Dicke Finn P. , Ruschewitz Uwe
Published: July 2024

A new MOF, named UoC‐11 (UoC=University of Cologne, [Mg4(3F‐BTB)2(OAc)2(DMF)6] ⋅  DMF), based on a fluorinated BTB (4,4′,4′′‐benzene‐1,3,5‐triyl‐tris‐(benzoate)) derivative and Mg cations was synthesized incorporating additional acetate anions. Its crystal structure was determined from single crystal X‐ray diffraction data (P21/c, Z=4). It consists of one‐dimensional Mg‐SBUs (strands), interconnected perpendicularly by tritopic linkers forming a dense two‐fold interpenetrating 3D network. Thus, only very small voids are formed which are fully occupied by the solvent. After activation at 150 °C (24 hours), no meaningful N2 adsorption was observed. Compared to the Ca and Sr analogues UoC‐9, UoC‐11 does not exhibit a crystal sponge behaviour. Thermal analysis (TGA) shows a release of all solvent molecules up to ~280 °C and the decomposition of the framework starts above 300 °C.
Epilogue: Bridging Past to Future—Small Analogy of Economic Crises
Authors: Schulte Volker , Köhle Ivan
Published: July 2024

In this epilogue, we would like to summarize economic crisis phenomena with a helicopter view, as it were, from the perspective of historical science. Many of them continue to shape the collective memory to this day.
Designing RS Approaches: Major Principles
Authors: Farooki Masuma
Published: July 2024

Based on the research and consultation findings of the RE-SOURCING Project, this chapter looks towards the future, reasoning that the knowledge and experience from the past decades need to be now consolidated by agreeing to a framework on how responsible sourcing approaches are developed, improved, and especially implemented. The framework allows decision-makers to step back from the detailed aspects of individual approaches and consolidate what they aim to achieve and how. The chapter framework requires stakeholders to consider a process where duty-bearers ensure policies, processes, and compliance mechanisms exist to deliver the environmental, social, and economic rights, as prioritised by stakeholders who are impacted by the activities within a mineral supply chain. This requires meaningful and inclusive participation and equal access to decision-making; accountability and a level playing field and transparency and access to information. While different stakeholders may take different paths to achieve this, it is essential that they share a common vision for responsible sourcing practices.
Unveiling the Anatomy of Adversarial Attacks: Concept-Based XAI Dissection of CNNs
Authors: Mikriukov Georgii , Schwalbe Gesina , Motzkus Franz , Bade Korinna
Published: July 2024

Adversarial attacks (AAs) pose a significant threat to the reliability and robustness of deep neural networks. While the impact of these attacks on model predictions has been extensively studied, their effect on the learned representations and concepts within these models remains largely unexplored. In this work, we perform an in-depth analysis of the influence of AAs on the concepts learned by convolutional neural networks (CNNs) using eXplainable artificial intelligence (XAI) techniques. Through an extensive set of experiments across various network architectures and targeted AA techniques, we unveil several key findings. First, AAs induce substantial alterations in the concept composition within the feature space, introducing new concepts or modifying existing ones. Second, the adversarial perturbation operation itself can be linearly decomposed into a global set of latent vector components, with a subset of these being responsible for the attack’s success. Notably, we discover that these components are target-specific, i.e., are similar for a given target class throughout different AA techniques and starting classes. Our findings provide valuable insights into the nature of AAs and their impact on learned representations, paving the way for the development of more robust and interpretable deep learning models, as well as effective defenses against adversarial threats.
A description of χcJ → VV decays within the effective field theory framework
Authors: Kivel Nikolay
Published: July 2024

Abstract

We study χcJ → VV decays using the QCD effective field theory approach. The helicity suppressed decay amplitudes are also considered. The colour-singlet contributions of these amplitudes suffer from the endpoint singularities, it is shown that they can be absorbed into renormalisation of the nonfactorisable colour-octet matrix element. The latter can be associated with the colour-octet component of the charmonium wave function. The heavy quark spin symmetry makes it possible to establish the relationships between colour-octet matrix elements for different states χcJ up to higher order corrections in small velocity v. This allows us to estimate the polarisation parameters for χc2→ VV using data for χc0,1→ VV. This analysis is carried out for the available data on the χcJ→ ϕϕ decays.
Risk and artificial general intelligence
Authors: Faroldi Federico L. G.
Published: July 2024

Artificial General Intelligence (AGI) is said to pose many risks, be they catastrophic, existential and otherwise. This paper discusses whether the notion of risk can apply to AGI, both descriptively and in the current regulatory framework. The paper argues that current definitions of risk are ill-suited to capture supposed AGI existential risks, and that the risk-based framework of the EU AI Act is inadequate to deal with truly general, agential systems.
Synthetic magnetic resonance-based relaxometry and brain volume: cutoff values for predicting neurocognitive outcomes in very preterm infants
Authors: Vanderhasselt Tim , Naeyaert Maarten , Buls Nico , Allemeersch Gert-Jan , Raeymaeckers Steven , Raeymaekers Hubert , Smeets Nathalie , Cools Filip , de Mey Johan , Dudink Jeroen
Published: July 2024

Background

Early neurorehabilitation can enhance neurocognitive outcomes in very preterm infants (<32 weeks), and conventional magnetic resonance imaging (MRI) is commonly used to assess neonatal brain injury; however, the predictive value for neurodevelopmental delay is limited. Timely predictive quantitative biomarkers are needed to improve early identification and management of infants at risk of neurodevelopmental delay.

Objective

To evaluate the potential of quantitative synthetic MRI measurements at term-equivalent age as predictive biomarkers of neurodevelopmental impairment and establish practical cutoff values to guide clinical decision-making.

Materials and methods

This retrospective study included 93 very preterm infants who underwent synthetic MRI at term-equivalent age between January 2017 and September 2020. Clinical outcomes were assessed using the Bayley-III scale of infant development (mean age 2.1 years). The predictive value for impaired development was analyzed using receiver operating characteristic curves for synthetic MRI-based volumetry and T1 and T2 relaxation measurements.

Results

The T1 relaxation time in the posterior limb of the internal capsule was a potent predictor of severe (sensitivity, 92%; specificity, 80%; area under the curve (AUC), 0.91) and mild or severe (AUC, 0.75) developmental impairment. T2 relaxation time in the posterior limb of the internal capsule was a significant predictor of severe impairment (AUC, 0.76), whereas the brain parenchymal volume was a significant predictor of severe (AUC, 0.72) and mild or severe impairment (AUC, 0.71) outperforming the reported qualitative MRI scores (AUC, 0.66).

Conclusion

The proposed cutoff values for T1 relaxation time in the posterior limb of the internal capsule and for total brain volume measurements, derived from synthetic MRI, show promise as predictors of both mild and severe neurodevelopmental impairment in very preterm infants.

Graphical Abstract
Emergencies in inflammatory rheumatic diseases
Authors: Auyezkhankyzy Dana , Izekenova Aigulsum , Kocyigit Burhan Fatih
Published: July 2024

Inflammatory rheumatic diseases (IRDs), encompassing a broad spectrum of chronic disorders, typically necessitate prolonged therapeutic intervention. Nevertheless, these diseases can sometimes manifest as severe emergencies requiring prompt and extensive medical intervention. Urgent intervention is essential for effectively recognizing and managing these situations, as they have the potential to be life-threatening and can result in severe morbidity and mortality. Emergencies in IRDs can occur with different frequencies and manifestations, including nervous system issues, severe infections, thrombosis-emboli, renal crises, gastrointestinal issues, and cardiovascular events. The fact that these events can occur across different IRDs underscores the necessity for heightened awareness and readiness among healthcare professionals. The pathophysiologic mechanisms that cause rheumatic emergencies are complex and involve multiple factors. These emergencies frequently arise due to the interplay between the inflammatory characteristics of rheumatic diseases and different systemic triggers. Early detection and treatment can have a substantial impact on an individual’s prognosis in cases of severe and life-threatening disorders that require prompt recognition. Rapid decision-making and urgent care are required to effectively address rheumatic emergencies, as well as the implementation of a diagnostic flowchart. This article provides an overview of the emergencies linked to IRDs, classifying and assessing them individually. This article aims to enhance healthcare professionals’ knowledge and awareness of critical situations by examining current recommendations and pathophysiological information. Implementing standardized diagnostic and treatment methods, providing patient education, and conducting continuing research into the underlying mechanisms are essential for enhancing the management of these critical situations and improving patient outcomes.
Impairment of the GABAergic system in the anterior insular cortex of heroin-addicted males
Authors: Gos Anna , Steiner Johann , Trübner Kurt , Mawrin Christian , Kaliszan Michał , Gos Tomasz
Published: July 2024

Opioid addiction is a global problem, causing the greatest health burden among drug use disorders, with opioid overdose deaths topping the statistics of fatal overdoses. The multifunctional anterior insular cortex (AIC) is involved in inhibitory control, which is severely impaired in opioid addiction. GABAergic interneurons shape the output of the AIC, where abnormalities have been reported in individuals addicted to opioids. In these neurons, glutamate decarboxylase (GAD) with its isoforms GAD 65 and 67 is a key enzyme in the synthesis of GABA, and research data point to a dysregulation of GABAergic activity in the AIC in opioid addiction. Our study, which was performed on paraffin-embedded brains from the Magdeburg Brain Bank, aimed to investigate abnormalities in the GABAergic function of the AIC in opioid addiction by densitometric evaluation of GAD 65/67-immunostained neuropil. The study showed bilaterally increased neuropil density in layers III and V in 13 male heroin-addicted males compared to 12 healthy controls, with significant U-test P values for layer V bilaterally. Analysis of confounding variables showed that age, brain volume and duration of formalin fixation did not confound the results. Our findings suggest a dysregulation of GABAergic activity in the AIC in opioid addiction, which is consistent with experimental data from animal models and human neuroimaging studies.
Reduction of detection limits in monitoring of internal exposures by a combined evaluation of emissions and spectra
Authors: Meisenberg Oliver
Published: July 2024

Routine monitoring of internal exposures requires the detection of effective doses of at most 1 mSv per calendar year. For some radionuclides, this requirement cannot be satisfied by a conventional evaluation of the spectra that are gained in alpha or gamma spectrometry. However, since several measurements are conducted per calendar year on a regular basis, a combined evaluation of measurements, i.e. the evaluation of sum spectra, is possible. Additionally, radionuclides that feature several emissions of alpha or gamma radiation allow a combined evaluation of their emissions. Both methods can lead to significantly smaller detection limits as compared to a separate evaluation of spectra in many cases. However, the variation of parameters that influence the evaluation such as the measurement efficiency, abundance and chemical yield requires specific calculations and treatments of the spectra as well as a manipulation of the channel contents: In a combination of emissions, energy regions are summed and evaluated with a combined efficiency that is weighted by the abundances. In a combination of spectra, the channel contents must be scaled by the ratio of the calibration factors before the summation of the spectra. In the routine monitoring of short-lived radionuclides that feature a variety of emissions such as 225Ac, these combinations are particularly effective in reducing the detectable annual effective dose. For alpha spectrometry of 225Ac, both methods applied together can lead to a detectable effective dose of about 1 mSv per year as compared to a dose of about 90 mSv with a conventional separate evaluation.
Exploring the potential of Lactocaseibacillus rhamnosus PMC203 in inducing autophagy to reduce the burden of Mycobacterium tuberculosis
Authors: Rahim Md Abdur , Seo Hoonhee , Kim Sukyung , Barman Indrajeet , Ghorbanian Fatemeh , Hossain Mohammed Solayman , Shuvo Md Sarower Hossen , Lee Saebim , Song Ho-Yeon
Published: July 2024

Mycobacterium tuberculosis, a lethal pathogen in human history, causes millions of deaths annually, which demands the development of new concepts of drugs. Considering this fact, earlier research has explored the anti-tuberculosis potential of a probiotic strain, Lactocaseibacillus rhamnosus PMC203, leading to a subsequent focus on the molecular mechanism involved in its effect, particularly on autophagy. In this current study, immunoblotting-based assay exhibited a remarkable expression of autophagy marker LC3-II in the PMC203 treated group compared to an untreated group. A remarkable degradation of p62 was also noticed within treated cells compared to control. Furthermore, the immunofluorescence-based assay showed significant fold change in fluorescence intensity for alexa-647-LC3 and alexa-488-LC3, whereas p62 was degraded noticeably. Moreover, lysosomal biogenesis generation was elevated significantly in terms of LAMP1 and acidic vesicular organelles. As a result, PMC203-induced autophagy played a vital role in reducing M. tuberculosis burden within the macrophages in treated groups compared to untreated group. A colony -forming unit assay also revealed a significant reduction in M. tuberculosis in the treated cells over time. Additionally, the candidate strain significantly upregulated the expression of autophagy induction and lysosomal biogenesis genes. Together, these results could enrich our current knowledge of probiotics-mediated autophagy in tuberculosis and suggest its implications for innovatively managing tuberculosis.
ZBTB7A regulates LncRNA HOTAIR-mediated ELAVL1/SOX17 axis to inhibit malignancy and angiogenesis in endometrial carcinoma
Authors: Zhang Xiao-Hui , Wu Shu-Wei , Feng Yi-Fan , Xie Yang-Qin , Li Min , Hu Ping , Cao Yunxia
Published: July 2024

Background

Endometrial cancer (EC) is the sixth most frequent cancer in women worldwide and has higher fatality rates. The pathophysiology of EC is complex, and there are currently no reliable methods for diagnosing and treating the condition. Long non-coding RNA (lncRNA), according to mounting evidence, is vital to the pathophysiology of EC. HOTAIR is regarded as a significant prognostic indicator of EC. ZBTB7A decreased EC proliferation and migration, according to recent studies, however the underlying mechanism still needs to be clarified.

Methods

The research utilized RT-qPCR to measure HOTAIR expression in clinical EC tissues and various EC cell lines. Kaplan-Meier survival analysis was employed to correlate HOTAIR levels with patient prognosis. Additionally, the study examined the interaction between ZBTB7A and HOTAIR using bioinformatics tools and ChIP assays. The experimental approach also involved manipulating the expression levels of HOTAIR and ZBTB7A in EC cell lines and assessing the impact on various cellular processes and gene expression.

Results

The study found significantly higher levels of HOTAIR in EC tissues compared to adjacent normal tissues, with high HOTAIR expression correlating with poorer survival rates and advanced cancer characteristics. EC cell lines like HEC-1 A and KLE showed higher HOTAIR levels compared to normal cells. Knockdown of HOTAIR in these cell lines reduced proliferation, angiogenesis, and migration. ZBTB7A was found to be inversely correlated with HOTAIR, and its overexpression led to a decrease in HOTAIR levels and a reduction in malignant cell behaviors. The study also uncovered that HOTAIR interacts with ELAVL1 to regulate SOX17, which in turn activates the Wnt/β-catenin pathway, promoting malignant behaviors in EC cells.

Conclusion

HOTAIR is a critical regulator in EC, contributing to tumor growth and poor prognosis. Its interaction with ZBTB7A and regulation of SOX17 via the Wnt/β-catenin pathway underlines its potential as a therapeutic target.
Targeting the PI3K/AKT/mTOR pathway offer a promising therapeutic strategy for cholangiocarcinoma patients with high doublecortin-like kinase 1 expression
Authors: Liang Ziwei , Ge Yang , Li Jianjian , Bai Yunting , Xiao Zeru , Yan Rui , An Guangyu , Zhang Donglei
Published: July 2024

Background

Cholangiocarcinoma (CCA), characterized by high heterogeneity and extreme malignancy, has a poor prognosis. Doublecortin-like kinase 1 (DCLK1) promotes a variety of malignant cancers in their progression. Targeting DCLK1 or its associated regulatory pathways can prevent the generation and deterioration of several malignancies. However, the role of DCLK1 in CCA progression and its molecular mechanisms remain unknown. Therefore, we aimed to investigate whether and how DCLK1 contributes to CCA progression.

Methods

The expression of DCLK1 in CCA patients was detected using Immunohistochemistry (IHC). We established DCLK1 knockout and DCLK1 overexpression cell lines for Colony Formation Assay and Transwell experiments to explore the tumor-promoting role of DCLK1. RT-PCR, Western blot and multiple fluorescent staining were used to assess the association between DCLK1 and epithelial–mesenchymal transition (EMT) markers. RNA sequencing and bioinformatics analysis were performed to identify the underlying mechanisms by which DCLK1 regulates CCA progression and the EMT program.

Results

DCLK1 was overexpressed in CCA tissues and was associated with poor prognosis. DCLK1 overexpression facilitated CCA cell invasion, migration, and proliferation, whereas DCLK1 knockdown reversed the malignant tendencies of CCA cells, which had been confirmed both in vivo and in vitro. Furthermore, we demonstrated that DCLK1 was substantially linked to the advancement of the EMT program, which included the overexpression of mesenchymal markers and the downregulation of epithelial markers. For the underlying mechanism, we proposed that the PI3K/AKT/mTOR pathway is the key process for the role of DCLK1 in tumor progression and the occurrence of the EMT program. When administered with LY294002, an inhibitor of the PI3K/AKT/mTOR pathway, the tumor’s ability to proliferate, migrate, and invade was greatly suppressed, and the EMT process was generally reversed.

Conclusions

DCLK1 facilitates the malignant biological behavior of CCA cells through the PI3K/AKT/mTOR pathway. In individuals with cholangiocarcinoma who express DCLK1 at high levels, inhibitors of the PI3K/AKT/mTOR signaling pathway may be an effective therapeutic approach.
Creep Versus Consolidation in Tunnelling through Squeezing Ground—Part B: Transferability of Experience
Authors: Nordas Alexandros N. , Leone Thomas , Anagnostou Georgios
Published: July 2024

This paper investigates potential differences between creep and consolidation in mechanised tunnelling through squeezing ground, placing focus on the practical question of using experiences gained from existing tunnels about the required thrust force as a reference for tunnels of different diameter or adjacent tunnels. The investigations focus on two aspects. First, the effect of the tunnel diameter on the risk of shield jamming is examined. The paper demonstrates that larger-diameter tunnels are more favourable in poor-quality ground, while the opposite holds in better-quality ground, as well as in the case of pronouncedly time-dependent ground behaviour due to consolidation or creep. Second, the effect of a tunnel on the required thrust force in a neighbouring tunnel built later is examined. The paper shows that this interaction effect is particularly important in water-bearing ground of low permeability, where the drainage action of the first tunnel induces pore pressure relief and ground consolidation in an extensive area, leading to a remarkable reduction of the thrust force in the second tunnel. Conversely, in the case of creep the interaction is negligible even under extremely squeezing conditions, due to the fundamentally different nature of the purely mechanical rheological processes from coupled hydromechanical processes. The presented investigations into the transferability of experiences are valuable for tunnelling practice, in cases of twin tunnels as well as in situations where a smaller-diameter tunnel is constructed prior to the main tunnel (e.g. a pilot tunnel for exploration, advance drainage or ground improvement), or also the opposite (e.g. upgrade of a road tunnel by later construction of a safety tunnel with a smaller diameter).
Deep Learning–Based Localization and Detection of Malpositioned Nasogastric Tubes on Portable Supine Chest X-Rays in Intensive Care and Emergency Medicine: A Multi-center Retrospective Study
Authors: Wang Chih-Hung , Hwang Tianyu , Huang Yu-Sen , Tay Joyce , Wu Cheng-Yi , Wu Meng-Che , Roth Holger R. , Yang Dong , Zhao Can , Wang Weichung , Huang Chien-Hua
Published: July 2024

Malposition of a nasogastric tube (NGT) can lead to severe complications. We aimed to develop a computer-aided detection (CAD) system to localize NGTs and detect NGT malposition on portable chest X-rays (CXRs). A total of 7378 portable CXRs were retrospectively retrieved from two hospitals between 2015 and 2020. All CXRs were annotated with pixel-level labels for NGT localization and image-level labels for NGT presence and malposition. In the CAD system, DeepLabv3 + with backbone ResNeSt50 and DenseNet121 served as the model architecture for segmentation and classification models, respectively. The CAD system was tested on images from chronologically different datasets (National Taiwan University Hospital (National Taiwan University Hospital)-20), geographically different datasets (National Taiwan University Hospital-Yunlin Branch (YB)), and the public CLiP dataset. For the segmentation model, the Dice coefficients indicated accurate delineation of the NGT course (National Taiwan University Hospital-20: 0.665, 95% confidence interval (CI) 0.630–0.696; National Taiwan University Hospital-Yunlin Branch: 0.646, 95% CI 0.614–0.678). The distance between the predicted and ground-truth NGT tips suggested accurate tip localization (National Taiwan University Hospital-20: 1.64 cm, 95% CI 0.99–2.41; National Taiwan University Hospital-Yunlin Branch: 2.83 cm, 95% CI 1.94–3.76). For the classification model, NGT presence was detected with high accuracy (area under the receiver operating characteristic curve (AUC): National Taiwan University Hospital-20: 0.998, 95% CI 0.995–1.000; National Taiwan University Hospital-Yunlin Branch: 0.998, 95% CI 0.995–1.000; CLiP dataset: 0.991, 95% CI 0.990–0.992). The CAD system also detected NGT malposition with high accuracy (AUC: National Taiwan University Hospital-20: 0.964, 95% CI 0.917–1.000; National Taiwan University Hospital-Yunlin Branch: 0.991, 95% CI 0.970–1.000) and detected abnormal nasoenteric tube positions with favorable performance (AUC: 0.839, 95% CI 0.807–0.869). The CAD system accurately localized NGTs and detected NGT malposition, demonstrating excellent potential for external generalizability.
Impact of organic and nanoparticle-selenium fortified larval weaning diet on survival, growth, gastrointestinal, and (GPx) activity of European Sea Bass (Dicentrarchus labrax) Larvae
Authors: El-Dahhar Alaa A. , Khaleefa Gomaa A. , El-Zaeem Samy Y. , Mourad Mona M. , Raheem Mohammed M. Abdel
Published: July 2024

The study involved three groups of six broodstock with a 1:1 male-to-female ratio. They were injected with 13 µg/kg LHRHa to stimulate spawning. We fed the broodstock three diets: a control diet without selenium, a diet containing 0.3 mg of nano-selenium /kg (N-Se), and a diet containing 4 mg of organic selenium /kg (O-Se). The broodstock diet consisted of equal parts of dry feed (45% protein), sardines, and squid. After being laid, the eggs were obtained from the collection ponds at the General Authority for Fisheries Development's fish hatchery and incubated until hatching. The larvae were given a micro diet containing 51.7% crude protein and live food (Rotifer and Artemia). Rotifer density increased from 5/ml to 15/ml by day 22 dph, Artemia nauplii increased from 0.2 to 4 ind./ml, from 7 to 35 dph then decreased to 0 at 55 dph, and micro-diets increased from 100-200 µ at 16 dph to 200-400 µ at 23-40 dph to 300-500 µ at 55 dph, and 500-1000 µ until the experiment ended. Three different diets in three replicates were tested: A micro diet free of selenium as a control diet (C), A micro diet with 0.3 mg of nano selenium (N-Se) kg-1, and A micro diet supplemented with organic selenium 4 mg (O-Se). Each group was taken from the three Broodstock groups respectively. Sixteen days after hatching, the three experimental micro diets were introduced to the larvae and continued for 76 days post-hatch. Larvae (260,000 per tank) were placed in fiberglass tanks with 4 m3 of water at a temperature of 19±2°C for optimal conditions. The larvae fed the N-Se diet had significantly better survival rates (75.0 ± 1.2 %), final body weight (240.0 ± 5.8 mg), weight gain (239.00 ± 5.8 mg), average daily gain (3.98±0.1mg), total length (39.0±0.06 mm), specific growth rate (9.133±0.04 %/day), feed intake (471.67±0.01 mg), and better feed conversion ratio (1.97±0.01) than the other groups (P < 0.05). The group provided with N-Se also had the highest levels of glutathione peroxidase enzyme (GPx) content in the whole larval body, whereas the control diet without Se supplementation recorded the lowest value of (14.8 ± 0.1 U/mg protein). The number and length of folds in the stomach and esophagus of sea bass post-larvae fed on diets fortified with selenium in both forms, nanoparticles or organic, showed a significant (P < 0.05) enhancement on the larval gastrointestinal (GI) tract. Moreover, selenium has an anti-inflammatory action in sea bass post-larvae. This study concluded that using N-Se as an antioxidant supports the growth and survival of European seabass D. labrax, gastrointestinal development and antioxidant efficacy during critical weaning.
A BRILLIANT-BRCA study: residual breast tissue after mastectomy and reconstruction
Authors: Kaidar-Person Orit , Faermann Renata , Polikar Dor , Cohen Kfir , Bernstein-Molho Rinat , Morrow Monica , Boersma Liesbeth Jorinne , Offersen Birgitte Vrou , Poortmans Philip , Sklair-Levy Miri , Anaby Debbie
Published: July 2024

Introduction

Different types of mastectomies leave different amounts of residual breast tissue. The significance of the residual breast volume (RBV) is not clear. Therefore, we developed an MRI tool that allows to easily assess the RBV. In this study we evaluated factors associated with RBV after skin or nipple sparing mastectomy (SSM/NSM) in breast cancer BRCA pathogenic variant (PV) carriers who underwent both therapeutic and risk reducing SSM/NSM and its relation to breast cancer outcomes using an innovative MRI-based tool.

Methods

Data of breast cancer BRCA PV who were treated between 2006 and 2020 were retrieved from of the oncogenetics unit databases. Only patients who underwent SSM/NSM and had a postoperative breast MRI available for analysis were included. Data collected included demographics, clinicopathological features, and outcomes. The MRI tool was developed by a breast cancer imaging laboratory. A logistic regression test and 95% confidence interval (CI) were used to assess the associated risk of increased RBV. A forward stepwise linear regression was used to correlate tumour-patient specific factors and RBV, and a Kaplan–Meier curve to show the probability of locoregional relapse.

Results

A total of 84 patients undergoing 89 mastectomies were included. At a median follow-up of 98 months, 5 local, 2 regional, and 4 distant recurrences were observed. RBV was not significantly related with breast cancer outcomes (p value = NS). A higher body mass index (BMI) was associated with a higher RBV (p < 0.0001). A larger number of involved axillary nodes was associated with a smaller RBV (p = 0.025). The RBV on the risk-reducing mastectomy side was significantly higher compared to the breast cancer side (p value = 0.007). Local recurrences occurred in the vicinity of the primary tumour.
Monitoring dynamics of biocrust rehabilitation in acid-saturated desert soils
Authors: Kerem T. , Nejidat A. , Zaady E.
Published: July 2024

The study explores the aftermath of a wastewater reservoir failure in a phosphate fertilizer industry, resulting in the release of acidic water containing phosphorus and sulfate compounds into the Ashalim stream’s Nature Reserve in the Judean desert, which affected the soil surface biological crusts (biocrusts) layer. The study aims to examine contamination effects on biocrusts over 3 years at two research sites along the stream, compare effects between contaminated sites, assess rehabilitation treatments, and examine their impact on soil characteristics. Hypotheses suggest significant damage to biocrusts due to acidic water flow, requiring human intervention for accelerated restoration. The results indicate adverse effects on biocrust properties, risking its key role in the desert ecosystem. The biocrust layer covering the stream’s ground surface suffered significant physical, chemical, and biological damage due to exposure to industrial process effluents. However, soil enrichment treatments, including biocrust components and organic material, show promising effects on biocrust recovery.
Assessment of spatio-temporal dynamics of land degradation and desertification in Pakistan and its impact on agriculture productivity
Authors: Hissan Riaz Ul , Shafiq Hamza , Nassani Abdelmohsen A. , Parveen Nusrat , Hussain Bilal , Radulescu Magdalena
Published: July 2024

Various natural and anthropogenic activities such as climate change, urbanization and industrialization play a vital role in changing the land characteristics. These changes does not only affect the human lives and activities, but also results in tremendous decrease in agricultural productivity and arable land. Thus, the purpose of this study is to analyze the land degradation and desertification in Pakistan using satellite imageries data acquired from the Landsat 8 and 9. For the empirical analysis, various indices such as Normalized Difference Vegetation Index, Normalized Difference Bare Soil Index, Supervised classification and Land Surface Temperature are examined using Google earth engine cloud computing platform. The results showed that desertified and built-up-land are increasing, while degraded land, arable land, and vegetative land are decreasing in the study area. Also, results of land surface temperature analysis showed a rise in the temperature up to 3.060C as compared to previous two years. Moreover, estimated findings from regression analysis showed that Normalized Difference Vegetation Index, and Normalized Difference Bare Soil Index positively affects the Land Surface Temperature. The findings of study are important for government and concern stakeholders to take necessary measures to stop the conversion of productive green land into unproductive degraded and desertified land.
Comparison between rupture parameters of intermediate and deep earthquakes at the Peru–Brazil–Bolivia border and northern Chile
Authors: Pro Carmen , Tavera Hernando , Mattesini Maurizio , Escudero Lucía , Buforn Elisa , Udías Agustín , Centeno Estela
Published: July 2024

We determined the main parameters of the source rupture process of intermediate- and deep-depth earthquakes occurring in the Peru–Brazil–Bolivia border region and northern Chile. The parameters of depth, fault-plane orientation, scalar seismic moment, slip distribution, and radiated seismic energy are obtained from seismograms. We selected 15 intermediate-depth earthquakes (100 km < h < 300 km) and 10 very deep earthquakes (h > 500 km) with magnitudes MW ≥ 6.0. For most events, the slip distribution over the rupture plane shows a single asperity, and the source time function presents a simple pulse. There are differences between intermediate-depth and deep earthquakes. The rupture areas, maximum slip and source time function (STF) duration are larger for intermediate-depth events than for deep events. Additionally, the STF’s show a sharper increase for deep earthquakes. The scaled radiated seismic energy shows larger values for deep depth events. The stress regime pattern derived from the obtained focal mechanism agrees with the geometry of the subduction of the Nazca plate. At intermediate depths, in the northern area up to 12°S, the stress pattern corresponds to a horizontal extension, while in the southern area, the tension axes dip at an angle of 30°. At deep depths, the stress regime corresponds to vertical compression in the north and dips of approximately 45° in the south.
Pharmacokinetic Modeling of the Effect of Tariquidar on Ondansetron Disposition into the Central Nervous System
Authors: Chiang Manting , Back Hyunmoon , Lee Jong Bong , Oh Sarah , Guo Tiffany , Girgis Simone , Park Celine , Haroutounian Simon , Kagan Leonid
Published: July 2024

Purpose

Serotonin (5-HT3) receptor antagonists are promising agents for treatment of neuropathic pain. However, insufficient drug exposure at the central nervous system (CNS) might result in lack of efficacy. The goal of this study was to evaluate the impact of administration of a Pgp inhibitor (tariquidar) on ondansetron exposure in the brain, spinal cord, and cerebrospinal fluid in a wild-type rat model.

Methods

Ondansetron (10 mg/kg) and tariquidar (7.5 mg/kg) were administered intravenously, plasma and tissue samples were collected and analyzed by HPLC. A mathematical model with brain, spinal cord, cerebrospinal fluid and two systemic disposition compartments was developed to describe the data.

Results

The results demonstrate that tariquidar at 7.5 mg/kg resulted in a complete inhibition of Pgp efflux of ondansetron in the brain and spinal cord. The compartmental model successfully captured pharmacokinetics of ondansetron in wild type and Pgp knockout (KO) animals receiving the drug alone or in wild type animals receiving the ondansetron and tariquidar combination.

Conclusions

The study provided important quantitative information on enhancement of CNS exposure to ondansetron using co-administration of Pgp Inhibitor in a rat model, which will be further utilized in conducting a clinical study. Tariquidar co-administration resulted in ondansetron CNS exposure comparable to observed in Pgp KO rats. Results also highlighted the effect of tariquidar on plasma disposition of ondansetron, which may not be dependent on Pgp inhibition, and should be evaluated in future studies.
Spatial Competition Models in Health Care Markets: A Review
Authors: Levaggi Laura , Levaggi Rosella
Published: July 2024

Through time, spatial competition has become the natural environment for studying a number of problems, ranging from product differentiation to mail order versus traditional business, to service provision under various assumptions about the institutional setting. Health economics research has greatly benefited from the intuitions that underlie the Hotelling model and several authors have contributed to the literature on the architecture of the market for health care by proposing models within this framework. In this paper we explore how spatial competition has been used in health economics to improve the knowledge of the mechanisms of the market for health care through the derivation of significant policy implications. One of the most important messages is that in spite of competition, the regulator still should have a central role in the architecture of the market and policies have to be carefully tailored in order to avoid the onset of perverse, undesired effects on quality and welfare.