bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating CCR6+ILC proportions are lower in multiple sclerosis patients
Authors: Aglas‐Leitner Florentina , Juillard Pierre , Juillard Anette , Byrne Scott N , Hawke Simon , Grau Georges E , Marsh‐Wakefield Felix 
Published: December 2022

AbstractObjectivesThe role of innate lymphoid cells (ILC), particularly helper ILC, in the pathogenesis of multiple sclerosis (MS) is not well understood. Here, we present a comprehensive analysis of peripheral ILC subsets in MS patients prior and after alemtuzumab administration using mass cytometry.MethodsCirculating ILC were analysed by mass cytometry in MS patients before and after alemtuzumab. These were compared with non‐MS controls. MS‐related shifts among ILC immunophenotypes were further elucidated by fast interpolation‐based t‐SNE (Flt‐SNE) dimensionality reduction.ResultsNeither natural killer (NK) cells nor helper ILC (ILC1, ILC2 and ILC3) levels were altered following alemtuzumab treatment. However, CD56bright NK cell expansions were observed in relapsing patients. MS patients prior to alemtuzumab further displayed proportional shifts from ILC1 to ILC2, with MS‐associated decreases in CCR6+ helper ILC proportions.ConclusionCD56bright NK cells during relapse indicate an immediate response to disease reactivation, while CCR6‐related shifts among helper ILC suggest altered ILC migration to the CNS during MS.
A novel endoscopic finding of a scratch sign is useful for evaluating the Helicobacter pylori infection status
Authors: Yada Tomoyuki , Itakura Yoshiyuki , Watanabe Ryo , Odaka Keita , Yagi Toyokazu , Ikegami Yurika , Sekine Katsunori , Uemura Naomi 
Published: December 2022

AbstractObjectivesDuring esophagogastroduodenoscopy, a red linear scrape‐like appearance with white deposits sometimes appears on the gastric mucosa at the lower greater curvature of the gastric body, a finding we named the “scratch sign.” We aimed to clarify the clinical significance of this new endoscopic finding in the endoscopic evaluation of the Helicobacter pylori infection status.MethodsAmong patients who underwent esophagogastroduodenoscopy at our hospital between October 2016 and June 2017, 437 patients were included in the study. We first examined the overall scratch sign positivity rate, and then this was compared according to the H. pylori infection status. Subsequently, other variables were compared and examined between the positive and negative scratch sign groups.ResultsOverall, 437 patients were included in the analysis. The scratch sign was observed in 1.4% of 71 patients with current infections, 26.9% of 290 patients with past infections, and 31.6% of 76 uninfected patients. In the multivariate analysis, H. pylori‐negative, severe gastric mucosal atrophy, and acid secretion depressant were independent factors that significantly affected the appearance of the scratch sign.ConclusionsA novel endoscopic finding, the scratch sign, was found to be a good endoscopic predictor of H. pylori‐negative gastric mucosa. Furthermore, combined with atrophic changes and xanthomas that persisted after eradication, these findings were found to be useful in accurately diagnosing H. pylori past‐infected gastric mucosa endoscopically.
Employing QbD strategies to assess the impact of cell viability and density on the primary recovery of monoclonal antibodies
Authors: Wohlenberg Ole Jacob , Kortmann Carlotta , Meyer Katharina V. , Scheper Thomas , Solle Dörte 
Published: December 2022

AbstractQuality by Design (QbD) is one of the most important tools for the implementation of Process Analytical Technology (PAT) in biopharmaceutical production. For optimal characterization of a monoclonal antibody (mAb) upstream process a stepwise approach was implemented. The upstream was divided into three process stages, namely inoculum expansion, production, and primary recovery, which were investigated individually. This approach enables analysis of process parameters and associated intermediate quality attributes as well as systematic knowledge transfer to subsequent process steps. Following previous research, this study focuses on the primary recovery of the mAb and thereby marks the final step toward a holistic characterization of the upstream process. Based on gained knowledge during the production process evaluation, the cell viability and density were determined as critical parameters for the primary recovery. Directed cell viability adjustment was achieved using cytotoxic camptothecin in a novel protocol. Additionally, the cell separation method was added to the Design of Experiments (DoE) as a qualitative factor and varied between filtration and centrifugation. To assess the quality attributes after cell separation, the bioactivity of the mAb was analyzed using a cell‐based assay and the purity of the supernatant was evaluated by measurement of process related impurities (host cell protein proportion, residual DNA). Multivariate data analysis of the compiled data confirmed the hypothesis that the upstream process has no significant influence on the bioactivity of the mAb. Therefore, process control must be tuned towards high mAb titers and purity after the primary recovery, enabling optimal downstream processing of the product. To minimize amounts of host cell proteins and residual DNA the cell viability should be maintained above 85% and the cell density should be controlled around 15 × 106 cells/ml during the cell removal. Thereby, this study shows the importance of QbD for the characterization of the primary recovery of mAbs and highlights the useful implementation of the stepwise approach over subsequent process stages.
Pesticide Prioritization by Potential Biological Effects in Tributaries of the Laurentian Great Lakes
Authors: Oliver Samantha K. , Corsi Steven R. , Baldwin Austin K. , Nott Michele A. , Ankley Gerald T. , Blackwell Brett R. , Villeneuve Daniel L. , Hladik Michelle L. , Kolpin Dana W. , Loken Luke , DeCicco Laura A. , Meyer Michael T. , Loftin Keith A. 
Published: December 2022

Abstract
Watersheds of the Great Lakes Basin (USA/Canada) are highly modified and impacted by human activities including pesticide use. Despite labeling restrictions intended to minimize risks to nontarget organisms, concerns remain that environmental exposures to pesticides may be occurring at levels negatively impacting nontarget organisms. We used a combination of organismal-level toxicity estimates (in vivo aquatic life benchmarks) and data from high-throughput screening (HTS) assays (in vitro benchmarks) to prioritize pesticides and sites of concern in streams at 16 tributaries to the Great Lakes Basin. In vivo or in vitro benchmark values were exceeded at 15 sites, 10 of which had exceedances throughout the year. Pesticides had the greatest potential biological impact at the site with the greatest proportion of agricultural land use in its basin (the Maumee River, Toledo, OH, USA), with 72 parent compounds or transformation products being detected, 47 of which exceeded at least one benchmark value. Our risk-based screening approach identified multiple pesticide parent compounds of concern in tributaries of the Great Lakes; these compounds included: eight herbicides (metolachlor, acetochlor, 2,4-dichlorophenoxyacetic acid, diuron, atrazine, alachlor, triclopyr, and simazine), three fungicides (chlorothalonil, propiconazole, and carbendazim), and four insecticides (diazinon, fipronil, imidacloprid, and clothianidin). We present methods for reducing the volume and complexity of potential biological effects data that result from combining contaminant surveillance with HTS (in vitro) and traditional (in vivo) toxicity estimates. Environ Toxicol Chem 2023;42:367–384. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Evaluation of Pediococcus acidilacticiAS185 as an adjunct culture in probiotic cheddar cheese manufacture
Authors: Wang Chao , Gao Lei , Gao Yansong , Yang Ge , Zhao Zijian , Zhao Yujuan , Wang Jihui , Li Shengyu 
Published: December 2022

AbstractA novel probiotic Pediococcus acidilactici AS185, isolated from traditional Chinese fermented foods, was used as an adjunct culture for probiotic cheddar cheese production. The physicochemical composition, textural, free amino acids (FAAs), short‐chain fatty acids (SCFAs) profiles, sensory properties, and microbial survival, was evaluated during the 90‐day ripening period. The addition of P. acidilactici AS185 did not influence the physicochemical composition of cheddar cheese but significantly decreased the hardness without affecting its textural profile. During ripening, P. acidilactici AS185 was able to grow and promote the generation of FAAs and SCFAs, but did not alter the overall sensory properties; it rather improved the flavor and taste of cheese. In addition, the cheese matrix protected strain P. acidilactici AS185 during transit throughout the simulated gastrointestinal system. These results demonstrated that P. acidilactici AS185 adjunct cultures might be useful for producing high‐quality probiotic cheddar cheese.
Preparation of oral nanoparticles of Perillae Fructus oil and prevention application of cold stress in mice
Authors: Xu Junfei , Zhang Jianxi , Lin Huiying , Zhang Jiayu , Zhou Rong , Wu Xianjin , Niu Youya , Zhang Juzuo 
Published: December 2022

AbstractPerillae Fructus oil has an important function in relieving cold stress. However, its application in this aspect has still been restricted because of instability and low bioavailability. In this study, Perillae Fructus oil was extracted through Soxhlet extraction, analyzed through gas chromatography–mass spectrometry (GC–MS), and nanopackaged into a yeast shell for the preparation of nanoparticles for oral administration. The characteristics of the nanoparticles were investigated using a Malvern zeta‐size nanoinstrument, scanning electron microscopy (SEM), and high‐performance liquid chromatography (HPLC). Then, the roles of orally administered nanoparticles in relieving cold stress were evaluated by investigating blood physiological and biochemical indexes in mice. The results showed that the oil yield from Perillae Fructus and shell yield from yeast cells were ~48.37% and ~16.87%, respectively. Approximately 89.21% of the added oil was packaged into the yeast shell to form nanoparticles with an average diameter of 316.74 nm and a surface charge of +2.9 mV. The nanoparticles were stable in simulated gastric acid and could be effectively released in simulated intestinal fluid with an efficiency of ~91.34%. After oral administration of nanoparticles, the mouse blood indexes of white blood cells (WBCs), superoxide dismutase (SOD) activity, and malonaldehyde (MDA) content were recovered compared to those in model mice, with a more remarkable effect than oral administration of free Perillae Fructus oil. Overall, the stability and bioavailability were improved by packaging Perillae Fructus oil into a yeast shell. These nanoparticles are a new agent for the prevention of cold stress.
Treatment outcomes and cost comparisons for older adults with T4 laryngeal squamous cell cancer
Authors: McDermott Jessica D. , Amini Arya , Molina Elizabeth , Stokes William A. , Karam Sana D. 
Published: December 2022

AbstractBackgroundTo evaluate treatment modalities of T4 larynx cancer in older adults using SEER‐Medicare.MethodsThe database was queried for patients aged 66 and older with nonmetastatic T4 laryngeal squamous cell cancer from 2006 to 2015. Treatment modalities compared were surgery plus chemoradiation (SCR), surgery plus radiation (SR), chemoradiation (CR), surgery (S), and radiation (R). Multivariate analysis and Kaplan–Meier methods were used to explore the relationship of treatment modality and survival. Total cancer‐related costs were calculated.ResultsA total of 438 patients met inclusion criteria. Patients receiving CR or SR had similar CSS to SCR (HR 1.36 and HR 1.24, respectively). Those receiving S (HR 2.00) or R (HR 2.41) had significantly worse CSS. Similar findings were observed for OS. Cancer care‐related costs were not significantly different but highest in SCR ($162215) and lowest in R ($121421).ConclusionOlder patients with T4 larynx cancer had similar survival rates when treated with CR, SR, and SCR. Average total health care costs were not significantly different between modalities. Patients not eligible for triple‐modality could consider these other treatment options.
Carbohydrate‐Derived Dienes as Building Blocks for Pharmaceutically Relevant Molecules
Authors: Dubbu Sateesh , Santhi Jampani , Hevey Rachel 
Published: December 2022

AbstractCarbohydrate‐based dienes are valuable building blocks for a variety of highly functionalized carbo‐ and oxa‐cycles by virtue of their high degree of inherent stereochemical information, and suitability in various synthetic transformations. Research into the chemistry of carbohydrate‐based dienes has been expanding over the last decades due to its unique applications in the construction of diverse and complex structural frameworks. In this review, we describe the main transformations of this interesting class of molecule and highlight their utility in the construction of diverse ring systems important for drug development.
Run‐up flow of MHD fluid between parallel porous plates in the presence of transverse magnetic field
Authors: Jha Basant K. , Jibril H. M. , Yusuf K. L. 
Published: December 2022

AbstractThis paper investigated the run‐up flow of magnetohydrodynamics (MHD) incompressible, viscous, Newtonian fluid bounded by two parallel horizontal porous plates in the presence of transverse magnetic field. The fluid flow is initially due to constant pressure gradient, placed parallel to the plates. On attaining steady state, the pressure gradient is suddenly withdrawn and the lower porous plate is set into motion in its own plane, this phenomenon is termed as run‐up flow. The transfer of momentum is as a result of the disturbances emanating from the boundary into the fluid. The initial value problem is solved using Laplace transform technique to obtain the closed‐form solution for the velocity in the Laplace domain. Semi‐analytical result is obtained by an inversion technique based on Riemann‐sum approximation to invert the solution for velocity into its corresponding time domain. The mathematical simulation conducted shows that increasing the Hartmann number is observed to decrease the fluid velocity while increasing the pressure gradient is found to enhance the fluid velocity. Furthermore, the opposing effects of suction/injection parameter on the fluid velocity have been established in the research.
Bacterial Quorum Sensing Signals at the Interdomain Interface
Authors: Laganenka Leanid , Sourjik Victor 
Published: December 2022

AbstractChemical interactions among microorganisms and between microorganisms and their hosts involve bidirectional release and sensing of various signalling molecules. Quorum sensing, mediated by small molecules termed autoinducers, is well known to be used by bacteria to coordinate their collective behaviours. However, there is a growing body of evidence suggesting that autoinducers are involved not only in intraspecies and interspecies communication among bacteria, but also in signalling interactions with eukaryotic hosts and even with phages. Although a clear picture is yet to emerge, in this minireview we briefly summarize recent advances in our understanding of interdomain signalling mediated by the major classes of the bacterial quorum sensing molecules, including its effects on the host cells and its potential physiological relevance.
EANet: Multiscale autoencoder based edge attention network for fluid segmentation from SD‐OCT images
Authors: Pappu Geetha Pavani , Tankala Sreekar , Talabhaktula Krishna , Biswal Birendra 
Published: December 2022

AbstractMacular edema is a retinal complication that occurs due to the presence of excess fluid between the retinal layers. This might lead to swelling in the retina and cause severe vision impairment if not detected in its early stages. This paper presents a robust Edge Attention network (EANet) for segmenting the different retinal fluids like Intraretinal Fluid (IRF), Subretinal Fluid (SRF), and Pigment Epithelial Detachment (PED) from the Spectral Domain – Optical Coherence Tomography (SD‐OCT) images. The proposed method employs a novel image enhancement technique by filtering OCT images using a BM3D (Block Matching and 3D Filtering) filter followed by Contrast Limited Adaptive Histogram Equalization (CLAHE) and a linear filter based on multivariate Taylor series to acquire the edge maps of the OCT images. A novel autoencoder based multiscale attention mechanism is incorporated with EANet that feeds on both the OCT image and edge‐enhanced OCT image at every level of the encoder. The proposed network, EANet, has been trained and tested for the segmentation of all three types of fluids on the RETOUCH challenge dataset, and the segmentation of the IRF on the OPTIMA challenge and DUKE DME datasets. The average dice coefficient of IRF, SRF, and PED for the RETOUCH dataset is 0.683, 0.873, and 0.756, respectively, whereas it is 0.805, 0.77, and 0.756 for Cirrus, Spectralis, and Topcon vendors, respectively. The proposed method outperformed all the teams that participated in the OPTIMA challenge on all types of vendor images in terms of dice coefficient. The average dice coefficients of IRF on the OPTIMA and DUKE DME datasets are 0.84 and 0.72, respectively.
Apigenin protects from hepatorenal damage caused by lead acetate in rats
Authors: Fehaid Alaa , Al‐Ghamdi Mohammad S. , Alzahrani Khalid J. , Theyab Abdulrahman , Al‐Amer Osama M. , Al‐Shehri Saad S. , Algahtani Mohammad , A. Oyouni Atif Abdulwahab , Alnfiai Mrim M. , Aly Mohamed H. , Alsharif Khalaf F. , Albrakati Ashraf , Kassab Rami B. , Althagafi Hussam A. , Alharthi Fahad , Abdel Moneim Ahmed E. , Lokman Maha S. 
Published: December 2022

AbstractExposure to lead (Pb) is associated with serious health problems including hepatorenal toxicity. Apigenin is a natural‐sourced flavonoid with promising antioxidant and anti‐inflammatory effects. In this research, we investigated the potential protective role of apigenin against lead acetate (PbAc)‐induced hepatorenal damage. Thus, this experiment studied the exposure of male Wistar Albino rats to apigenin and/or PbAc and their effects in comparison to the control rats. Apigenin administration decreased the levels of Pb and prevented the histopathological deformations in liver and kidney tissues following PbAc exposure. This was confirmed by the normalized levels of liver and kidney function markers. Additionally, apigenin inhibited significantly oxidative reactions through upregulating Nrf2 and HO‐1, and activating their downstreamed antioxidants accompanied by a marked depletion of pro‐oxidants. Moreover, apigenin decreased the elevated pro‐inflammatory cytokines and inhibited cell loss in liver and kidney tissues in response to PbAc intoxication in both tissues. The obtained results demonstrated that apigenin could be used to attenuate the molecular, biochemical, and histological alterations associated with Pb exposure due to its potent antioxidant, anti‐inflammatory, and antiapoptotic effects.
Arsenic‐induced toxicity and the ameliorative role of antioxidants and natural compounds
Authors: Shiek Sadiya S. , Sajai Sanai T. , Dsouza Herman S. 
Published: December 2022

AbstractArsenic (As) poisoning has proven to be a major threat worldwide because of its toxic effects on the human body. As toxicity through drinking water is a global health concern. The toxicity of As is known to affect the liver, kidney, lungs, muscles, cardiovascular system, and nervous system and can even induce diabetes. Further As can cause skin lesions leading to notable diseases in the skin like Bowen's disease. Chronic exposure to As has caused many tragedies in Eastern, and several Southeast Asian and Latin American countries. Long‐term exposure to As makes it an immediate threat that should be dealt with as a priority, and one of the ways to handle it may be with the use of antioxidants. In this review, we have discussed the natural and anthropogenic sources of As, its metabolism, pathophysiology, and mechanism of toxicity. Besides, we have also discussed some of the synthetic chelators and the ameliorative role of antioxidants and natural compounds in reducing As toxicity.
An integrated investigation of structural and pathway alteration caused by PIK3CA and TP53 mutations identified in cfDNA of metastatic breast cancer
Authors: R. Hephzibah Cathryn , Kumar S. Udhaya , R. Gnanasambandan , Naayanan P. Jeyaprakash , Sathiyarajeswaren P. , Devi M. S. Shree , K. Satish Srinivas , Doss C. George Priya 
Published: December 2022

AbstractIn peripheral blood, cell‐free DNA (cfDNA) contains circulating tumor DNA (ctDNA), which indicates molecular abnormalities in metastatic breast tumor tissue. The sequencing of cfDNA of Metastatic Breast Cancer (MBC) patients allows assessment of therapy response and noninvasive treatment. In the proposed study, clinically significant alterations in PIK3CA and TP53 genes associated with MBC resulting in a missense substitution of His1047Arg and Arg282Trp from an next‐generation sequencing‐based multi‐gene panel were reported in a cfDNA of a patient with MBC. To investigate the impact of the reported mutation, we used molecular docking, molecular dynamics simulation, network analysis, and pathway analysis. Molecular Docking analysis determined the distinct binding pattern revealing H1047R‐ATP complex has a higher number of Hydrogen bonds (H‐bonds) and binding affinity with a slight difference compared to the PIK3CA‐ATP complex. Following, molecular dynamics simulation for 200 ns, of which H1047R‐ATP complex resulted in the instability of PIK3CA. Similarly, for TP53 mutant R282W, the zinc‐free state (apo) and zinc‐bounded (holo) complexes were investigated for conformational change between apo and holo complexes, of which the holo complex mutant R282W was unstable. To validate the conformational change of PIK3CA and TP53, 80% mutation of H1047R in the kinase domain of p110α expressed ubiquitously in PIK3CA protein that alters PI3K pathway, while R282W mutation in DNA binding helix (H2) region of P53 protein inhibits the transcription factor in P53 pathway causing MBC. According to our findings, the extrinsic (hypoxia, oxidative stress, and acidosis); intrinsic factors (MYC amplification) in PIK3CA and TP53 mutations will provide potential insights for developing novel therapeutic methods for MBC therapy.