bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Potential of Black Soldier Fly Larval Proteins as Bioactive Peptide Sources through in Silico Gastrointestinal Proteolysis: A Cheminformatic Investigation
Authors: Wong Fai-Chu , Lee You-Han , Ong Joe-Hui , Manan Fazilah Abd , Sabri Mohamad Zulkeflee , Chai Tsun-Thai
Published: March 2023

Despite their potential as a protein source for human consumption, the health benefits of black soldier fly larvae (BSFL) proteins following human gastrointestinal (GI) digestion are poorly understood. This computational study explored the potential of BSFL proteins to release health-promoting peptides after human GI digestion. Twenty-six proteins were virtually proteolyzed with GI proteases. The resultant peptides were screened for high GI absorption and non-toxicity. Shortlisted peptides were searched against the BIOPEP-UWM and Scopus databases to identify their bioactivities. The potential of the peptides as inhibitors of myeloperoxidase (MPO), NADPH oxidase (NOX), and xanthine oxidase (XO), as well as a disruptor of Keap1–Nrf2 protein–protein interaction, were predicted using molecular docking and dynamics simulation. Our results revealed that about 95% of the 5218 fragments generated from the proteolysis of BSFL proteins came from muscle proteins. Dipeptides comprised the largest group (about 25%) of fragments arising from each muscular protein. Screening of 1994 di- and tripeptides using SwissADME and STopTox tools revealed 65 unique sequences with high GI absorption and non-toxicity. A search of the databases identified 16 antioxidant peptides, 14 anti-angiotensin-converting enzyme peptides, and 17 anti-dipeptidyl peptidase IV peptides among these sequences. Results from molecular docking and dynamic simulation suggest that the dipeptide DF has the potential to inhibit Keap1–Nrf2 interaction and interact with MPO within a short time frame, whereas the dipeptide TF shows promise as an XO inhibitor. BSFL peptides were likely weak NOX inhibitors. Our in silico results suggest that upon GI digestion, BSFL proteins may yield high-GI-absorbed and non-toxic peptides with potential health benefits. This study is the first to investigate the bioactivity of peptides liberated from BSFL proteins following human GI digestion. Our findings provide a basis for further investigations into the potential use of BSFL proteins as a functional food ingredient with significant health benefits.
Emerging Therapeutic Approaches to Target the Dark Side of Senescent Cells: New Hopes to Treat Aging as a Disease and to Delay Age-Related Pathologies
Authors: Khalil Roula , Diab-Assaf Mona , Lemaitre Jean-Marc
Published: March 2023

Life expectancy has drastically increased over the last few decades worldwide, with important social and medical burdens and costs. To stay healthy longer and to avoid chronic disease have become essential issues. Organismal aging is a complex process that involves progressive destruction of tissue functionality and loss of regenerative capacity. One of the most important aging hallmarks is cellular senescence, which is a stable state of cell cycle arrest that occurs in response to cumulated cell stresses and damages. Cellular senescence is a physiological mechanism that has both beneficial and detrimental consequences. Senescence limits tumorigenesis, lifelong tissue damage, and is involved in different biological processes, such as morphogenesis, regeneration, and wound healing. However, in the elderly, senescent cells increasingly accumulate in several organs and secrete a combination of senescence associated factors, contributing to the development of various age-related diseases, including cancer. Several studies have revealed major molecular pathways controlling the senescent phenotype, as well as the ones regulating its interactions with the immune system. Attenuating the senescence-associated secretory phenotype (SASP) or eliminating senescent cells have emerged as attractive strategies aiming to reverse or delay the onset of aging diseases. Here, we review current senotherapies designed to suppress the deleterious effect of SASP by senomorphics or to selectively kill senescent cells by “senolytics” or by immune system-based approaches. These recent investigations are promising as radical new controls of aging pathologies and associated multimorbidities.
Role of Histone Variant H2A.J in Fine-Tuning Chromatin Organization for the Establishment of Ionizing Radiation-Induced Senescence
Authors: Abd Al-razaq Mutaz A. , Freyter Benjamin M. , Isermann Anna , Tewary Gargi , Mangelinck Adèle , Mann Carl , Rübe Claudia E.
Published: March 2023

Purpose: Radiation-induced senescence is characterized by profound changes in chromatin organization with the formation of Senescence-Associated-Heterochromatin-Foci (SAHF) and DNA-Segments-with-Chromatin-Alterations-Reinforcing-Senescence (DNA-SCARS). Importantly, senescent cells also secrete complex combinations of pro-inflammatory factors, referred as Senescence-Associated-Secretory-Phenotype (SASP). Here, we analyzed the epigenetic mechanism of histone variant H2A.J in establishing radiation-induced senescence. Experimental Design: Primary and genetically-modified lung fibroblasts with down- or up-regulated H2A.J expression were exposed to ionizing radiation and were analyzed for the formation of SAHF and DNA-SCARS by immunofluorescence microscopy. Dynamic changes in chromatin organization and accessibility, transcription factor recruitment, and transcriptome signatures were mapped by ATAC-seq and RNA-seq analysis. The secretion of SASP factors and potential bystander effects were analyzed by ELISA and RT-PCR. Lung tissue of mice exposed to different doses were analyzed by the digital image analysis of H2A.J-immunohistochemistry. Results: Differential incorporation of H2A.J has profound effects on higher-order chromatin organization and on establishing the epigenetic state of senescence. Integrative analyses of ATAC-seq and RNA-seq datasets indicate that H2A.J-associated changes in chromatin accessibility of regulatory regions decisively modulates transcription factor recruitment and inflammatory gene expression, resulting in an altered SASP secretome. In lung parenchyma, pneumocytes show dose-dependent H2A.J expression in response to radiation-induced DNA damage, therefore contributing to pro-inflammatory tissue reactions. Conclusions: The fine-tuned incorporation of H2A.J defines the epigenetic landscape for driving the senescence programme in response to radiation-induced DNA damage. Deregulated H2A.J deposition affects chromatin remodeling, transcription factor recruitment, and the pro-inflammatory secretome. Our findings provide new mechanistic insights into DNA-damage triggered epigenetic mechanisms governing the biological processes of radiation-induced injury.
Oscillatory Deficits in the Sub-Chronic PCP Rat Model for Schizophrenia Are Reversed by mGlu5 Receptor-Positive Allosteric Modulators VU0409551 and VU0360172
Authors: Brown Jessica , Grayson Ben , Neill Joanna C. , Harte Michael , Wall Mark J. , Ngomba Richard T.
Published: March 2023

The cognitive deficits of schizophrenia are linked to imbalanced excitatory and inhibitory signalling in the prefrontal cortex (PFC), disrupting gamma oscillations. We previously demonstrated that two mGlu5 receptor-positive allosteric modulators (PAMs), VU0409551 and VU0360172, restore cognitive deficits in the sub-chronic PCP (scPCP) rodent model for schizophrenia via distinct changes in PFC intracellular signalling molecules. Here, we have assessed ex vivo gamma oscillatory activity in PFC slices from scPCP rats and investigated the effects of VU0409551 and VU0360172 upon oscillatory power. mGlu5 receptor, protein kinase C (PKC), and phospholipase C (PLC) inhibition were also used to examine ‘modulation bias’ in PAM activity. The amplitude and area power of gamma oscillations were significantly diminished in the scPCP model. Slice incubation with either VU0409551 or VU0360172 rescued scPCP-induced oscillatory deficits in a concentration-dependent manner. MTEP blocked the PAM-induced restoration of oscillatory power, confirming the requirement of mGlu5 receptor modulation. Whilst PLC inhibition prevented the power increase mediated by both PAMs, PKC inhibition diminished the effects of VU0360172 but not VU0409551. This aligns with previous reports that VU0409551 exhibits preferential activation of the phosphatidylinositol-3-kinase (PI3K) signalling pathway over the PKC cascade. Restoration of the excitatory/inhibitory signalling balance and gamma oscillations may therefore underlie the mGluR5 PAM-mediated correction of scPCP-induced cognitive deficits.
The Anti-Inflammatory Peptide TnP Is a Candidate Molecule for Asthma Treatment
Authors: Lima Carla , Falcão Maria Alice Pimentel , Pinto Felipe Justiniano , Bernardo Jefferson Thiago Gonçalves , Lopes-Ferreira Monica
Published: March 2023

Asthma is the most common chronic lung disease, with increasing morbidity and mortality worldwide. Accumulation of peribronchial leukocytes is the hallmark of asthma, in particular, eosinophils, which have been reported as the primary cell associated with the induction of airway hyperresponsiveness. Continued exacerbation and accumulation of other leukocytes, such as neutrophils, Th1, and Th17 cells correlate with many of the long-term effects of asthma, such as airway remodeling. We have patented the TnP family of synthetic cyclic peptides, which is in the preclinical phase of developmental studies for chronic inflammatory diseases. The aim of this work was to investigate whether TnP could show anti-inflammatory activity in a murine model of asthma that includes a mixed phenotype of eosinophilic and neutrophilic inflammation. For this, Balb/c mice, sensitized with OVA and exposed to 1% challenge with OVA aerosol, were submitted to prophylactic treatment, receiving TnP at 0.3 mg/kg orally, 1 h before each challenge. We found that sensitized mice challenged with OVA and treated with TnP showed no airway hyperreactivity or lung remodeling. TnP acts systemically in secondary lymphoid organs and locally in the lung, inhibiting the production of Th2/Th17 cytokines. Furthermore, TnP prevented the infiltration of eosinophils and neutrophils in the BAL and lung tissue, inhibited the production of IgE/IgG1, prevented hyperplasia of mucus-producing cells, and decreased the thickening and deposition of sub-epithelial collagen. Our results showed TnP as a candidate molecule for the treatment of airway remodeling associated with inflammatory diseases, such as asthma.
Light as a Modulator of Non-Image-Forming Brain Functions—Positive and Negative Impacts of Increasing Light Availability
Authors: Campbell Islay , Sharifpour Roya , Vandewalle Gilles
Published: March 2023

Light use is rising steeply, mainly because of the advent of light-emitting diode (LED) devices. LEDs are frequently blue-enriched light sources and may have different impacts on the non-image forming (NIF) system, which is maximally sensitive to blue-wavelength light. Most importantly, the timing of LED device use is widespread, leading to novel light exposure patterns on the NIF system. The goal of this narrative review is to discuss the multiple aspects that we think should be accounted for when attempting to predict how this situation will affect the NIF impact of light on brain functions. We first cover both the image-forming and NIF pathways of the brain. We then detail our current understanding of the impact of light on human cognition, sleep, alertness, and mood. Finally, we discuss questions concerning the adoption of LED lighting and screens, which offer new opportunities to improve well-being, but also raise concerns about increasing light exposure, which may be detrimental to health, particularly in the evening.
Research of On-Line Monitoring Technology Based on Laser Triangulation for Surface Morphology of Extreme High-Speed Laser Cladding Coating
Authors: Wang Jing , Ai Chao , Guo Fei , Yun Xiao , Zhu Xun
Published: March 2023

This work aims to develop a novel method for on-line monitoring of coating quality during the Extreme High-speed Laser Cladding (EHLA) process. JG-11 coating was prepared by EHLA, and microstructure, microhardness, corrosion performance, and scratch resistance were investigated. To analyze the influences of fluctuations in processing parameters on coating quality, a single-factor experiment scheme was designed and an on-line monitoring system based on laser triangulation was built. Furthermore, a new forming method for the surface profile of EHLA coating was proposed, and a new comprehensive evaluation index of surface morphology was accordingly designed. Benefitting from the extremely high cooling rate, EHLA JG-11 coating had fine grains, high hardness, and better corrosion resistance and scratch resistance than those of Electroplating Hard Chromium (EHC). The results revealed that the surface morphologies presented different characteristics due to the fluctuations of process parameters, such as high surface flatness, deep pits, small peaks, poor directionality, etc. The comprehensive evaluation index composed of Sa, Ssk, and Str could effectively characterize the surface morphology of EHLA coating, which proved that the monitoring system and evaluation method could realize on-line monitoring of the process parameters during the EHLA process.
Structure, Electrochemical, and Transport Properties of Li- and F-Modified P2-Na2/3Ni1/3Mn2/3O2 Cathode Materials for Na-Ion Batteries
Authors: Chen Xinglong , Guo Wenyue , Li Rui , Du Peng , Zhan Xiaowen , Gao Shan
Published: March 2023

The development of cobalt-free P2-Na2/3Ni1/3Mn2/3O2 cathodes is hampered by poor electrochemical performance, resulting from structural instability during high-voltage cycling. Herein, Li+ and F− ions are introduced simultaneously via a simple sol–gel method. The F not only enters the lattice but forms chemically stable NaF on the surface. The modified electrode delivered significantly better electrochemical performance than the pristine one, including much-enhanced capacity retention (64% vs. 36%, 100 cycles) at 0.5 C and a four-time higher capacity output at 10 C. The ex situ XRD and in situ Raman analysis revealed cyclability enhancement mechanisms in terms of inhibiting the P2–O2 phase transition and Na+/vacancy ordering. The conductivity measurements (based on AC impedance and DC polarization) and GITT analysis proved, on both bulk material and electrode levels, that Na+ conduction and, thus, rate performance is notably promoted by doping. The individual contribution of Li and F to the overall performance improvement was also discussed. Furthermore, a solid-state sodium-metal battery was successfully demonstrated with the modified cathode. The above results verify that Li+/F− incorporation can enable enhancements in both cyclability and rate capability of the P2-Na2/3Ni1/3Mn2/3O2 cathodes and are expected to provide a new perspective for the rational design of high-performance layered oxide cathode materials for progressive sodium-ion batteries.
Transparent Films Thickness Mapping Highlighting the Viscosity Effect of Elastic Layers Made by Sol–Gel Process with an In-House Ellipsometer
Authors: Guillot Océane , Guediche Amira , Lafarie Mathieu , Moiny Amandine , Brockhouse Théo , Piombini Hervé
Published: March 2023

New optical coatings are currently developed to mitigate the shockwave generated by nanosecond lasers in high-power laser systems such as the MegaJoule laser (LMJ). These shockwaves seem responsible for the damage growth observed on optical components. A possible solution for shockwave mitigation is using ormosil (organically modified silicate) coatings made by the sol–gel method with thicknesses of a few microns. Unfortunately, the sol–gel solution exhibits a viscous behavior, and thus, the deposited layers are heterogeneous in thickness. An experimental ellipsometer has been designed to measure this heterogeneity and highlight the viscoelastic properties of the layers responsible for self-healing effects that were observed when these layers were scratched. This ellipsometer allows us to know the refractive index of the coating and therefore its density. Density and thickness are the two essential parameters for determining the speed of sound and the modulus of elasticity of the layer, which indicate the ability of the layer to attenuate more or less elastic waves or shock waves.
Luminescence Properties of Y3F[Si3O10]:Ln3+ (Ln = Eu, Tb, Er) with Thalenite-Type Host Lattice and Crystal Structure of Tm3F[Si3O10]
Authors: Schäfer Marion , Petter Michael , Hartenbach Ingo , Locke Ralf , Zhang Shuang , Wickleder Claudia , Schleid Thomas
Published: March 2023

With Tm3F[Si3O10], a new representative of the Ln3F[Si3O10] series could be synthesized by the reaction of Tm2O3, TmF3 and SiO2 (molar ratio: 1:1:3), applying an excess of CsBr as a fluxing agent in gas-tightly sealed platinum crucibles for eight days at 750 °C, and designed to yield Tm3F3[Si3O9] or Cs2TmF[Si4O10]. Single crystals of Tm3F[Si3O10] (monoclinic, P21/n; a = 725.04(6), b = 1102.43(9), c = 1032.57(8) pm, β = 97.185(7)°; Z = 4) appear as pale celadon, transparent, air- and water-resistant rhombic plates. According to its thalenite-type structure, Tm3F[Si3O10] contains catena-trisilicate anions [Si3O10]8− and triangular [FTm3]8+ cations. The three crystallographically different Tm3+ cations are coordinated by seven plus one (Tm1) or only seven anions (Tm2 and Tm3) exhibiting a single F− anion for each polyhedron, additional to the majority of O2− anions. Furthermore, the luminescence properties of the isotypic colorless compound Y3F[Si3O10] doped with Eu3+ (red emission), Tb3+ (green emission) and Er3+ (yellow and infrared emission), respectively, are reported in presenting their different excitation and emission spectra.
Effect of Mineral-Generated Lithium Slag on the Properties of Magnesium Oxychloride Cement
Authors: Li Shitong , Liu Siru , Du Yongsheng , Huang Qing , Qu Wenhui , Zheng Weixin
Published: March 2023

A large amount of mineral-generated lithium slag will be produced after extracting lithium from spodumene. However, most lithium slag has not been well utilized. In this study, lithium slag was added to MOC, and its setting time, compressive strength, water resistance, phase composition, and microscopic morphology were studied. The results showed that although lithium slag prolonged the setting time and reduced the compressive strength of MOC, its water resistance improved. When the content of lithium slag was 20 wt%, the softening coefficient of the specimen reached a maximum value, and the softening coefficients at 3, 7, and 14 days were 1.47, 1.91, and 1.51 times that of MOC without lithium slag, respectively. A microscopic morphology analysis showed that the lithium slag transformed the MOC crystals from needle-like to column-like or block-like, the crystallization range expanded, and the binding force weakened. Magnesium oxychloride cement with excellent mechanical properties and good workability was combined with magnesium slag in this paper to provide the basis for the application of magnesium slag in building materials.
Facile Synthesis of Al-20Si@Al2O3 Nanosheets Composite Powders and Its Refinement Performance on Primary Silicon in Al-20Si Alloy
Authors: Yu Kunliang , Su Jiahao , Liu Mengchen , Li Chengdong , Lin Yuhui , Zhao Mei , Hao Chuncheng
Published: March 2023

In this work, Al(OH)3 nanosheets are synthesized in situ on the surface of an Al-20Si alloy via the water bath method, and Al–20Si@Al2O3 composites are then obtained after calcination. The growth mechanism of the Al(OH)3 nanosheets is revealed, and a pathway is demonstrated to obtain Al–20Si@Al2O3 nanosheets with the desired structure and thickness. Furthermore, the influence of different Al–20Si@Al2O3 contents on the primary silicon phase in the Al–20Si alloy is investigated, and the mechanism of such an influence is theoretically analyzed. The mechanical properties of the modified Al–20Si alloy are tested, and the effects of the morphology and particle size of the silicon phase on the alloy properties are studied. The results show that Al–20Si@Al2O3 synthesized in situ by water bath has good dispersion in the melt. There is a lot of γ-Al2O3 dispersed in the matrix of the alloy, and the primary silicon of the Al-20Si alloy is obviously refined. By increasing the content of the modifier, the average size of primary silicon decreases first and then increases. When 15 wt% of the modifier is added, the refinement effect of primary silicon reaches its peak, and the size of primary silicon is reduced from unmodified 86.4 μm to 28.5 μm. The hardness and tensile strength of 75.2 HB and 120.3 MPa are increased to 107.2 HB and 185.9 Mpa by 42% and 55%, respectively. Compared with adding γ-Al2O3 directly, this experiment provides a simple method to synthesize the modifier, and γ-Al2O3 can be dispersed evenly in the aluminium-silicon alloy melt more easily by in-situ generation, without ultrasonic treatment or other ways. During mass production, the cost can be better controlled and good results can be achieved at the same time.
Assessment of the Genetic Diversity and Population Structure of the Peruvian Andean Legume, Tarwi (Lupinus mutabilis), with High Quality SNPs
Authors: Huaringa-Joaquin Amelia , Saldaña Carla L. , Saravia David , García-Bendezú Sady , Rodriguez-Grados Pedro , Salazar Wilian , Camarena Felix , Injante Pedro , Arbizu Carlos I.
Published: March 2023

Lupinus mutabilis Sweet (Fabaceae), “tarwi” or “chocho”, is an important grain legume in the Andean region. In Peru, studies on tarwi have mainly focused on morphological features; however, they have not been molecularly characterized. Currently, it is possible to explore the genetic parameters of plants with reliable and modern methods such as genotyping by sequencing (GBS). Here, for the first time, we used single nucleotide polymorphism (SNP) markers to infer the genetic diversity and population structure of 89 accessions of tarwi from nine Andean regions of Peru. A total of 5922 SNPs distributed along all chromosomes of tarwi were identified. STRUCTURE analysis revealed that this crop is grouped into two clusters. A dendrogram was generated using the UPGMA clustering algorithm and, like the principal coordinate analysis (PCoA), it showed two groups that correspond to the geographic origin of the tarwi samples. AMOVA showed a reduced variation between clusters (7.59%) and indicated that variability within populations is 92.41%. Population divergence (Fst) between clusters 1 and 2 revealed low genetic difference (0.019). We also detected a negative Fis for both populations, demonstrating that, like other Lupinus species, tarwi also depends on cross-pollination. SNP markers were powerful and effective for the genotyping process in this germplasm. We hope that this information is the beginning of the path towards a modern genetic improvement and conservation strategies of this important Andean legume.
A Qualitative Exploration of Conflicts in Human-Wildlife Interactions in Namibia’s Kunene Region
Authors: Luetkemeier Robert , Kraus Ronja , Mbidzo Meed , Hauptfleisch Morgan , Liehr Stefan , Blaum Niels
Published: March 2023

Wildlife numbers are declining globally due to anthropogenic pressures. In Namibia, however, wildlife populations increased with policy instruments that allow private ownership and incentivize their sustainable use. Antithetically, this resulted in increased resource competition between humans and wildlife and triggered conflicts among various stakeholder groups. This paper summarizes the results of a qualitative exploration of conflicts in wildlife management in Namibia’s Kunene Region, adjacent to Etosha National Park. We conducted a workshop and expert interviews with stakeholders from relevant sectors. Our qualitative research sheds light on societal conflicts over wildlife that originate from diverging interests, livelihood strategies, moral values, knowledge holders, personal relations and views on institutional procedures. We frame our insights into conflicting human–wildlife interactions with theoretical concepts of social-ecological systems, ecosystem services and ecosystem disservices and open the floor for quantitative assessments. Overall, our results may present a suitable way of understanding biodiversity conflicts in a theoretical way.
Navigating Storms: Examining Vultures’ Behavior in Response to Extreme Weather Events
Authors: Naveda-Rodríguez Adrián , Rush Scott A.
Published: March 2023

Extreme weather events such as hurricanes and tornadoes have been found to change the spatial and temporal abundance of raptors by decreasing survival and forcing the emigration of individuals, or by increasing habitat heterogeneity and facilitating recolonization of disturbed areas. Nonetheless, little is known about how extreme weather events could affect raptors’ movements and their space use in areas disturbed by large-scale weather events. We studied how extreme weather affected the movements of black and turkey vultures (Coragyps atratus and Cathartes aura, respectively) in Mississippi, USA, facing Hurricane Zeta in November 2020, winter storm Viola in February 2021, and tornados MS-43 and MS-44 in May 2021. We GPS-tracked 28 vultures in the paths of these events. We compared movement rates, net-squared displacements, and use of forest cover, before, during, and after the events. Since storm avoidance behavior has been observed in other birds, we expected that vultures would shift their movements out of the path of these events before storms hit. Further, we forecasted that vultures would make greater use of forested areas as protection against harsh conditions such as strong winds and heavy rain. Vultures responded differently to each weather event; they shifted their movements out of the predicted path of the hurricane and tornadoes but not the snowstorm. These findings reveal that both species use avoidance behavior and adjust their navigation and hazard detection accordingly. Avoidance behavior was more pronounced in turkey vultures than in black vultures. In general, vultures did not make greater use of forest areas as we expected, but turkey vultures did select forest areas during the snowstorm. We propose that olfaction and audition may be key in vultures’ response to extreme weather events.
A Review of the Patentability of Rosemary-Derived Drugs and Bioactive Compounds
Authors: El Boukhari Reda , Fatimi Ahmed
Published: March 2023

We reviewed the patentability of rosemary-derived drugs and bioactive compounds over the last 20 years and analyzed patent documents related to the rosemary (Rosmarinus officinalis Linné) plant using patent analysis techniques. A total of 12,320 patent documents (patent applications and granted patents) were identified, with China having the highest number of patent documents at 4384. The year 2017 had the most patent documents (1122). Patent classification codes indicate that most inventions are for medicinal preparations and cosmetics characterized by their composition. Further, expert driving forces and knowledge clusters showed that research and development has focused on methods to bring pharmaceutical products into specific physical or administering forms, which are described in the majority of patents. To demonstrate the innovation trends in rosemary-derived drugs and bioactive compounds, a selection of relevant patent documents, with publication dates between 2002 and 2022, is described at the end of the study. This selection contains a total of 13 patent documents, including six patent applications and seven granted patents, and deals with pharmaceutical and biomedical applications, processes for extracting rosemary-derived biomolecules (e.g., rosmarinic acid, carnosic acid, and carnosol), and cosmetic and food applications.
Uncertainty-Aware Deep Learning Classification of Adamantinomatous Craniopharyngioma from Preoperative MRI
Authors: Prince Eric W. , Ghosh Debashis , Görg Carsten , Hankinson Todd C.
Published: March 2023

Diagnosis of adamantinomatous craniopharyngioma (ACP) is predominantly determined through invasive pathological examination of a neurosurgical biopsy specimen. Clinical experts can distinguish ACP from Magnetic Resonance Imaging (MRI) with an accuracy of 86%, and 9% of ACP cases are diagnosed this way. Classification using deep learning (DL) provides a solution to support a non-invasive diagnosis of ACP through neuroimaging, but it is still limited in implementation, a major reason being the lack of predictive uncertainty representation. We trained and tested a DL classifier on preoperative MRI from 86 suprasellar tumor patients across multiple institutions. We then applied a Bayesian DL approach to calibrate our previously published ACP classifier, extending beyond point-estimate predictions to predictive distributions. Our original classifier outperforms random forest and XGBoost models in classifying ACP. The calibrated classifier underperformed our previously published results, indicating that the original model was overfit. Mean values of the predictive distributions were not informative regarding model uncertainty. However, the variance of predictive distributions was indicative of predictive uncertainty. We developed an algorithm to incorporate predicted values and the associated uncertainty to create a classification abstention mechanism. Our model accuracy improved from 80.8% to 95.5%, with a 34.2% abstention rate. We demonstrated that calibration of DL models can be used to estimate predictive uncertainty, which may enable clinical translation of artificial intelligence to support non-invasive diagnosis of brain tumors in the future.
Pregnancy-Specific Glycoprotein 9 Enhances Store-Operated Calcium Entry and Nitric Oxide Release in Human Umbilical Vein Endothelial Cells
Authors: Qin Ying , Meng Qinggang , Wang Qunhua , Wu Mingzhu , Fang Yan , Tu Chengcheng , Hu Xinyang , Shen Bing , Chen Hongbo , Xu Xiaohong
Published: March 2023

We explored changes in pregnancy-specific glycoprotein 9 (PSG9) levels in the serum of patients with preeclampsia and the effects and underlying mechanisms of PSG9 effects on calcium (Ca2+) homeostasis and nitric oxide (NO) release in human umbilical vein endothelial cells (HUVECs). Western blotting was used to detect protein expression levels, and an NO fluorescence probe was used to examine NO production. Intracellular Ca2+ concentrations were measured using a Ca2+-sensitive fluorescent dye under a fluorescence microscope. Compared with those in healthy pregnant women, serum PSG9 levels were significantly decreased in patients with preeclampsia. PSG9 (0.1 μg/mL) treatment of HUVECs significantly enhanced the expression levels of store-operated calcium entry (SOCE) channel proteins Orai1 and Orai2, but not Orai3, and of endothelial nitric oxide synthase (eNOS) and NO production. Pretreatment with an inhibitor of SOCE (BTP2) abolished PSG9-enhanced Orai1, Orai2, and eNOS expression levels and NO production in HUVECs. The mechanisms underlying SOCE that were PSG9 enhanced in HUVECs appear to involve the Ca2+/eNOS/NO signaling pathway. These findings suggest that serum PSG9 levels may be a potential biomarker for monitoring the occurrence or development of preeclampsia in pregnancy and that PSG9 may be a potential therapeutic target for the treatment of preeclampsia.
Correlation between Lower Esophageal Sphincter Metrics on High-Resolution Manometry and the Clinical Presentation of Patients with Newly Diagnosed Achalasia
Authors: Cohen Daniel L. , Avivi Eyal , Bermont Anton , Shibli Fahmi , Azzam Narges , Hijazi Basem , Baker Fadi Abu , Richter Vered , Shirin Haim , Mari Amir
Published: March 2023

Background: Achalasia is characterized by aperistalsis with poor relaxation of the lower esophageal sphincter (LES). We aimed to systematically assess whether LES metrics on high-resolution manometry (HRM) correlate with the symptomatic or endoscopic presentation of patients with achalasia. Methods: A retrospective study was performed at two tertiary medical centers. All cases of newly diagnosed, untreated achalasia were reviewed for demographics, symptoms, and endoscopic findings. These were correlated with HRM metrics, including LES basal pressure (LESP), integrated relaxation pressure (IRP), percent LES relaxation, and esophagogastric junction (EGJ) morphology. Results: 108 achalasia patients were included; 56 (51.9%) were men, with a mean overall age of 55.6 ± 17.9 years old. Achalasia subtypes included 23.1% with Type I, 65.7% Type II, and 11.1% Type III. Mean LESP was 40.9 ± 13.7 mmHg, IRP 26.8 ± 11.5 mmHg, with 36% ± 20% LES relaxation. On univariate analyses, a higher IRP was associated with age < 50 (p = 0.028), female sex (p = 0.030), Arab ethnicity (p < 0.001), weight loss (p = 0.016), a tortuous esophagus (p = 0.036), and resistance at the EGJ (p = 0.033). However, on multivariate regression analyses, only ethnicity remained significantly associated with IRP. No unique variables were associated with either LESP or percent LES relaxation. Achalasia subtype and Eckardt score were not associated with any LES metrics. Non-Type 1 EGJ morphology was associated with a lower LESP. Conclusions: LES metrics on HRM do not appear to correlate with the clinical or endoscopic presentation of patients with untreated achalasia.
Performance of VIDAS® Diagnostic Tests for the Automated Detection of Dengue Virus NS1 Antigen and of Anti-Dengue Virus IgM and IgG Antibodies: A Multicentre, International Study
Authors: Versiani Alice F. , Kaboré Antoinette , Brossault Ludovic , Dromenq Loïc , dos Santos Thayza M. I. L. , Milhim Bruno H. G. A. , Estofolete Cássia F. , Cissé Assana , Sorgho Pegdwendé Abel , Senot Florence , Tessonneau Marie , Diagbouga Serge , Nogueira Mauricio L.
Published: March 2023

Dengue is a serious mosquito-transmitted disease caused by the dengue virus (DENV). Rapid and reliable diagnosis of DENV infection is urgently needed in dengue-endemic regions. We describe here the performance evaluation of the CE-marked VIDAS® dengue immunoassays developed for the automated detection of DENV NS1 antigen and anti-DENV IgM and IgG antibodies. A multicenter concordance study was conducted in 1296 patients from dengue-endemic regions in Asia, Latin America, and Africa. VIDAS® dengue results were compared to those of competitor enzyme-linked immunosorbent assays (ELISA). The VIDAS® dengue assays showed high precision (CV ≤ 10.7%) and limited cross-reactivity (≤15.4%) with other infections. VIDAS® DENGUE NS1 Ag showed high positive and negative percent agreement (92.8% PPA and 91.7% NPA) in acute patients within 0–5 days of symptom onset. VIDAS® Anti-DENGUE IgM and IgG showed a moderate-to-high concordance with ELISA (74.8% to 90.6%) in post-acute and recovery patients. PPA was further improved in combined VIDAS® NS1/IgM (96.4% in 0–5 days acute patients) and IgM/IgG (91.9% in post-acute patients) tests. Altogether, the VIDAS® dengue NS1, IgM, and IgG assays performed well, either alone or in combination, and should be suitable for the accurate diagnosis of DENV infection in dengue-endemic regions.
Lung Ultrasound Artifacts Interpreted as Pathology Footprints
Authors: Demi Marcello , Soldati Gino , Ramalli Alessandro
Published: March 2023

Background: The original observation that lung ultrasound provides information regarding the physical state of the organ, rather than the anatomical details related to the disease, has reinforced the idea that the observed acoustic signs represent artifacts. However, the definition of artifact does not appear adequate since pulmonary ultrasound signs have shown valuable diagnostic accuracy, which has been usefully exploited by physicians in numerous pathologies. Method: A specific method has been used over the years to analyze lung ultrasound data and to convert artefactual information into anatomical information. Results: A physical explanation of the genesis of the acoustic signs is provided, and the relationship between their visual characteristics and the surface histopathology of the lung is illustrated. Two important sources of potential signal alteration are also highlighted. Conclusions: The acoustic signs are generated by acoustic traps that progressively release previously trapped energy. Consequently, the acoustic signs highlight the presence of acoustic traps and quantitatively describe their distribution on the lung surface; they are not artifacts, but pathology footprints and anatomical information. Moreover, the impact of the dynamic focusing algorithms and the impact of different probes on the visual aspect of the acoustic signs should not be neglected.
Low MTUS1 Protein Expression Is Associated with Poor Survival in Patients with Colorectal Adenocarcinoma
Authors: Park Hosub , Jee Seungyun , Son Hwangkyu , Cha Hyebin , Bang Seongsik , Ahn Byung Kyu , Myung Jaekyung , Paik Seungsam , Kim Hyunsung
Published: March 2023

Introduction: Microtubule-associated tumor suppressor 1 (MTUS1) is a novel tumor suppressor protein involved in cell proliferation, migration, and tumor growth. MTUS1 is thought to be downregulated in various human cancers and associated with poor prognosis. We evaluated the clinicopathologic significance and prognostic value of MTUS1 in colorectal adenocarcinoma. Methods: Immunohistochemical staining for MTUS1 was performed on tissue microarrays of 393 colorectal adenocarcinoma cases, and MTUS1 staining was classified into high- and low-expression groups. Then, we investigated the correlations between MTUS1 protein expression and various clinicopathological parameters and patient survival. Results: MTUS1 protein was expressed at various grade levels in the cytoplasm of tumor cells, which showed loss or decreased expression of MTUS1. A total of 253 cases (64.4%) were classified into the low MTUS1 protein expression group and 140 cases (35.6%) into the high MTUS1 expression group. A low level of MTUS1 protein significantly correlated with tumor size (p = 0.047), histological grade (p < 0.001), lymphovascular invasion (p < 0.001), perineural invasion (p = 0.047), and lymph node metastasis (p < 0.001). Survival analyses showed that patients with low MTUS1 protein expression had worse overall survival (p = 0.007, log-rank test) and worse recurrence-free survival (p = 0.019, log-rank test) than those with high MTUS1 expression. Conclusions: Low MTUS1 protein expression is associated with adverse clinicopathological characteristics and poor survival outcomes in patients with colorectal adenocarcinoma. These results suggest that MTUS1 functions as a tumor suppressor in colorectal adenocarcinoma and could be a potential prognostic biomarker.
Demystifying the Role of Prognostic Biomarkers in Breast Cancer through Integrated Transcriptome and Pathway Enrichment Analyses
Authors: Mishra Divya , Mishra Ashish , Nand Rai Sachchida , Vamanu Emanuel , Singh Mohan P.
Published: March 2023

Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of death in women. Researchers have discovered an increasing number of molecular targets for BC prognosis and therapy. However, it is still urgent to identify new biomarkers. Therefore, we evaluated biomarkers that may contribute to the diagnosis and treatment of BC. We searched TCGA datasets and identified differentially expressed genes (DEGs) by comparing tumor (100 samples) and non-tumor (100 samples) tissues using the Deseq2 package. Pathway and functional enrichment analysis of the DEGs was performed using the DAVID (Database for Annotation, Visualization, and Integrated Discovery) database. The protein–protein interaction (PPI) network was identified using the STRING database and visualized through Cytoscape software. Hub gene analysis of the PPI network was completed using cytohubba plugins. The associations between the identified genes and overall survival (OS) were analyzed using a Kaplan–Meier plot. Finally, we have identified hub genes at the transcriptome level. A total of 824 DEGs were identified, which were mostly enriched in cell proliferation, signal transduction, and cell division. The PPI network comprised 822 nodes and 12,145 edges. Elevated expression of the five hub genes AURKA, BUB1B, CCNA2, CCNB2, and PBK are related to poor OS in breast cancer patients. A promoter methylation study showed these genes to be hypomethylated. Validation through genetic alteration and missense mutations resulted in chromosomal instability, leading to improper chromosome segregation causing aneuploidy. The enriched functions and pathways included the cell cycle, oocyte meiosis, and the p53 signaling pathway. The identified five hub genes in breast cancer have the potential to become useful targets for the diagnosis and treatment of breast cancer.
A Cross-Sectional Study on the Prevalence and Risk Stratification of Chronic Kidney Disease in Cardiological Patients in São Paulo, Brazil
Authors: Samaan Farid , Damiani Bruna Bronhara , Kirsztajn Gianna Mastroianni , Sesso Ricardo
Published: March 2023

Chronic kidney disease (CKD) provides a worse prognosis for patients with heart disease. In Latin America, studies that analyzed the prevalence and risk stratification of CKD in this population are scarce. We aimed to evaluate CKD prevalence and risk categories in patients of a public referral cardiology hospital in São Paulo, Brazil. This was a cross-sectional study based on a laboratory database. Outpatient serum creatinine and proteinuria results performed between 1 January 2021 and 31 December 2021 were analyzed. CKD was defined by estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and proteinuria, by the albumin/creatinine ratio in a spot urine sample (UACR) >30 mg/g. A total of 36,651 adults were identified with serum creatinine levels (median age 72.4 [IQR, 51.0–73.6] years, 51% male). Among them, 51.9% had UACR dosage (71.5% with UACR < 30 mg/g, 22.6%, between 30–300 mg/g, and 5.9% with UACR > 300 mg/g). The prevalence of CKD was 30.9% (15.3% stage 3a, 10.2% stage 3b, 3.6% stage 4, and 1.7% stage 5), and the distribution of patients in the risk categories of the disease was: 52.0% with low-risk, 23.5%, moderate risk, 13.0%, high risk, and 11.2%, very high. In an outpatient setting, the prevalence of CKD in cardiological patients was almost three times (31%) that of the general population; about half of the individuals evaluated (48%) were not screened for an important risk marker (proteinuria), and approximately a quarter of these patients (24%) were in the high or very high CKD risk categories.
Management of Traumatic Femur Fractures: A Focus on the Time to Intramedullary Nailing and Clinical Outcomes
Authors: Ghouri Syed Imran , Mustafa Fuad , Kanbar Ahad , Al Jogol Hisham , Shunni Adam , Almadani Ammar , Abdurraheim Nuri , Goel Atirek Pratap , Abdelrahman Husham , Babikir Elhadi , Ramzee Ahmed F. , Ahmed Khalid , Alhardallo Mutaz , Asim Mohammad , Al-Thani Hassan , El-Menyar Ayman
Published: March 2023

Background: Femur shaft factures (FSF) are common injuries following high-energy mechanisms mainly involving motor vehicle crashes (MVC). We evaluated the timings of nailing management and analyzed the pattern of fracture union and outcome in a level 1 trauma center. Methods: This was a retrospective observational study of all the admitted trauma patients who sustained femoral fractures between January 2016 and September 2020. Data were analyzed and compared based on time to Intramedullary Nailing (IMN) (<12 h, 12–24 h and >24 h) and outcomes of FSF (union, delayed union and nonunion). Results: A total of 668 eligible patients were included in the study, of which the majority were males (90.9%) with a mean age of 34.5 ± 15.8, and 54% of the injuries were due to MVCs. The chest (35.8%) was the most commonly associated injured body region, followed by the pelvis (25.9%) and spine (25.4%). Most of femur fractures (93.3%) were unilateral, and 84.4% were closed fractures. The complete union of fractures was observed in 76.8% of cases, whereas only 4.2% and 3.3% cases had delayed union and nonunion, respectively, on the clinical follow-up. Patients in the delayed IMN (>24 h) were severely injured, had bilateral femur fracture (p = 0.001) and had higher rate of external fixation, blood transfusion, pulmonary complications and prolonged hospitalization. Non-union proportion was greater in those who had IMN <24 h, whereas a delayed union was greater in IMN done after 24 h (p = 0.5). Those with a nonunion femur fracture were more likely to have bilateral fracture (p = 0.003), frequently had retrograde nailing (p = 0.01), and high-grade femur fracture (AO type C; p = 0.04). Conclusion: This study showed that femur fracture is not uncommon (8.9%), which is manifested with the variety of clinical characteristics, depending on the mechanism, management and outcome in our center. Bilateral fracture, retrograde nailing and AO classification type C were the significant risk factors of non-union in patients with diaphyseal fractures. The timing of IMN has an impact on the fracture union; however, it is not a statistically significant difference. Therefore, the treating physicians should consider the potential risk factors for a better outcome by careful selection of treatment in sub-groups of patients.
Management of Oral Hygiene in Head-Neck Cancer Patients Undergoing Oncological Surgery and Radiotherapy: A Systematic Review
Authors: Lanzetti Jacopo , Finotti Federica , Savarino Maria , Gassino Gianfranco , Dell’Acqua Alessandro , Erovigni Francesco M.
Published: March 2023

Background: In the literature, among oral health prevention programs dedicated to cancer patients, a wide heterogeneity is evident. The purpose of this work is to analyze the available scientific evidence for the treatment of head and neck cancer (HNC) patients undergoing resective surgery and radiotherapy and to draw up a diversified oral hygiene protocol during oncological therapy. Methods: PubMed was used as database. Studies published from 2017 to September 2022 were analyzed. Studies investigating the effectiveness of the preventive procedures carried out by the dental professionals in HNC patients undergoing postoperative adjuvant therapy have been taken into account. Results: The application of the search string on PubMed allowed the selection of 7184 articles. The systematic selection of articles led to the inclusion of 26 articles in this review, including 22 RCTs, 3 observational studies, and 1 controlled clinical study. Articles were divided according to the debated topic: the management of radiation-induced mucositis, xerostomia, the efficacy of an oral infection prevention protocol, and the prevention of radiation-induced caries. Conclusions: Dental hygienists are fundamental figures in the management of patients undergoing oncological surgery of the maxillofacial district. They help the patient prevent and manage the sequelae of oncological therapy, obtaining a clear improvement in the quality of life.