bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pitavastatin induces caspase‐mediated apoptotic death through oxidative stress and DNA damage in combined with cisplatin in human cervical cancer cell line
Authors: Hacıseyitoğlu Aysun Ökçesiz , Doğan Tuğbagül Çal , Dilsiz Sevtap Aydın , Canpınar Hande , Eken Ayşe , Bucurgat Ülkü Ündeğer 
Published: December 2023

AbstractPitavastatin (PITA) is a 3‐hydroxy‐3‐methylglutaryl‐CoA (HMG‐CoA) reductase inhibitor to treat hypercholesterolemia and in recent studies is focused that its potential anti‐cancer effect. This study was aimed to elucidate the effect of PITA alone and in combination with cisplatin on cervical cancer cells (HeLa) in vitro. Cytotoxicity of PITA (5–200 μM) was evaluated by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) and neutral red uptake (NRU) assays for 24, 48, and 72 h. Cell apoptosis and cell cycle analyses were performed in flow cytometry (0.1–100 μM). The evaluation of genotoxic effects and oxidative DNA damage of PITA (2–200 μM) were performed with standard comet assay, formamidopyrimidine glycosylase (fpg)‐modified comet assay, and reactive oxygen species (ROS) activation in HeLa cells. PITA alone reduced cell viability in a dose‐dependent manner (20–200, 20–200, and 5–200 μM for 24, 48, and 72 h, respectively, in MTT). The combined treatment of PITA with cisplatin resulted in significantly greater inhibition of cell viability. ROS and DNA damage increased significantly at 100 μM for 4 h and 20 μM for 24 h, respectively. PITA‐induced apoptosis, an increased proportion of sub G1 cells, was monitored, and also, it increased the expression of active caspase‐9 and caspase‐3 and upregulated cleaved poly adenosine diphosphate ribose polymerase (PARP) by western blotting and caspase 3/8/9 multiple assay kit. We conclude that PITA can be used to efficiently cervical cancer studies, and promising findings have been obtained for further studies.
7,8‐dihydroxyflavone displayed antioxidant effect through activating HO‐1 expression and inhibiting caspase‐3/PARP activation in RAW264.7 cells
Authors: Chen Ting‐Xiao , Wang Shou‐Kai , Zhang Yu‐Qing , Wang Wei , Wang Qi , Yu Jian‐Chun , Zhao Sheng‐Chen , Xi Gao‐Lei , Jin Zhen , Chen Ze‐Shao , Tang You‐Zhi 
Published: December 2023

AbstractFlavonoids, which contain a benzo‐γ‐pyrone (C6–C3–C6) skeleton, have been reported to exhibit effective antioxidant ability. This study aimed to compare the antioxidant activities of 7,8‐dihydroxyflavone (7,8‐DHF) and 7‐hydroxyflavone (7‐HF) in H2O2, lipopolysaccharide (LPS), or tert‐butyl hydroperoxide (t‐BHP)‐induced RAW264.7 cells, respectively. The antioxidant capacities of 7,8‐DHF and 7‐HF were firstly evaluated by 2,2‐azinobis‐3‐ethyl‐benzothiazoline‐6‐sulphonic acid (ABTS), 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Then, reactive oxygen species (ROS), super oxide dismutase (SOD), and malondialdehyde (MDA) productions in H2O2, LPS, or t‐BHP‐induced RAW264.7 cells were tested and compared, respectively. Finally, the antioxidant mechanisms of 7‐HF and 7,8‐DHF were initially investigated by western blot. Our results showed that 7,8‐DHF possessed stronger free‐radical scavenging capacity than 7‐HF. Both 7,8‐DHF and 7‐HF suppressed MDA production and ROS accumulation, improved the activity of SOD in H2O2, LPS, or t‐BHP‐induced RAW264.7 cells, respectively. And 7,8‐DHF exerted a better antioxidant effect than 7‐HF, especially in t‐BHP‐induced oxidative stress. Mechanically, 7,8‐DHF prevented the activation of poly ADP‐ribosepolymerase and caspase‐3, meanwhile markedly upregulated the expression of HO‐1 protein in t‐BHP‐induced oxidative stress. These results suggested that 7,8‐DHF might serve as a potential pharmaceutical drug against oxidative stress injury.
A clinically relevant large‐scale biomanufacturing workflow to produce natural killer cells and natural killer cell‐derived extracellular vesicles for cancer immunotherapy
Authors: St‐Denis‐Bissonnette Frederic , Cummings Sarah E. , Qiu Shirley , Stalker Andrew , Muradia Gauri , Mehic Jelica , Mediratta Karan , Kaczmarek Shelby , Burger Dylan , Lee Seung‐Hwan , Wang Lisheng , Lavoie Jessie R. 
Published: December 2023

AbstractNatural killer cell‐derived extracellular vesicles (NK‐EVs) have shown promising potential as biotherapeutics for cancer due to their unique attributes as cytotoxic nanovesicles against cancer cells and immune‐modulatory activity towards immune cells. However, a biomanufacturing workflow is needed to produce clinical‐grade NK‐EVs for pre‐clinical and clinical applications. This study established a novel biomanufacturing workflow using a closed‐loop hollow‐fibre bioreactor to continuously produce NK‐EVs from the clinically relevant NK92‐MI cell line under serum‐free, Xeno‐free and feeder‐free conditions following GMP‐compliant conditions. The NK92 cells grown in the bioreactor for three continuous production lots resulted in large quantities of both NK cell and NK‐EV biotherapeutics at the end of each production lot (over 109 viable cells and 1013 EVs), while retaining their cytotoxic payload (granzyme B and perforin), pro‐inflammatory cytokine (interferon‐gamma) content and cytotoxicity against the human leukemic cell line K562 with limited off‐target toxicity against healthy human fibroblast cells. This scalable biomanufacturing workflow has the potential to facilitate the clinical translation of adoptive NK cell‐based and NK‐EV‐based immunotherapies for cancer with GMP considerations.
Strengthening the directed Brooks' theorem for oriented graphs and consequences on digraph redicolouring
Authors: Picasarri‐Arrieta Lucas 
Published: December 2023

AbstractLet be a digraph. We define as the maximum of and as the maximum of . It is known that the dichromatic number of is at most . In this work, we prove that every digraph which has dichromatic number exactly must contain the directed join of and for some such that , except if in which case must contain a digon. In particular, every oriented graph with has dichromatic number at most . Let be an oriented graph of order such that . Given two 2‐dicolourings of , we show that we can transform one into the other in at most steps, by recolouring exactly one vertex at each step while maintaining a dicolouring at any step. Furthermore, we prove that, for every oriented graph on vertices, the distance between two ‐dicolourings is at most when . We then extend a theorem of Feghali, Johnson and Paulusma to digraphs. We prove that, for every digraph with and every , the ‐dicolouring graph of consists of isolated vertices and at most one further component that has diameter at most , where is a constant depending only on .
Metabolic alterations unravel the maternofetal immune responses with disease severity in pregnant women infected with SARS‐CoV‐2
Authors: Hora Sandhya , Pahwa Prabhjyoti , Siddiqui Hamda , Saxena Anoushka , Kashyap Minal , Sevak Jayesh K. , Singh Ravinder , Javed Maryam , Yadav Pushpa , Kale Pratibha , Ramakrishna Gayatri , Bajpai Meenu , Rathore Asmita , Maras Jaswinder S. , Tyagi Shakun , Sarin Shiv K. , Trehanpati Nirupama 
Published: December 2023

AbstractPregnancy being an immune compromised state, coronavirus disease of 2019 (COVID‐19) disease poses high risk of premature delivery and threat to fetus. Plasma metabolome regulates immune cellular responses, therefore we aimed to analyze the change in plasma secretome, metabolome, and immune cells with disease severity in COVID‐19 positive pregnant females and their cord blood. COVID‐19 reverse transcriptase‐polymerase chain reaction positive pregnant females (n = 112) with asymptomatic (Asy) (n = 82), mild (n = 21), or moderate (n = 9) disease, healthy pregnant (n = 18), COVID‐19 positive nonpregnant females (n = 7) were included. Eighty‐two cord blood from COVID‐19 positive and seven healthy cord blood were also analyzed. Mother's peripheral blood and cord blood were analyzed for untargeted metabolome profiling and cytokines by using high‐resolution mass spectrometry and cytokine bead array. Immune scan was performed only in mothers' blood by flow cytometry. In Asy severe acute respiratory syndrome coronavirus 2 infection, the amino acid metabolic pathways such as glycine, serine, l‐lactate, and threonine metabolism were upregulated with downregulation of riboflavin and tyrosine metabolism. However, with mild‐to‐moderate disease, the pyruvate and nicotinamide adenine dinucleotide (NAD+) metabolism were mostly altered. Cord blood mimicked the mother's metabolomic profiles by showing altered valine, leucine, isoleucine, glycine, serine, threonine in Asy and NAD+, riboflavin metabolism in mild and moderate. Additionally, with disease severity tumor necrosis factor‐α, interferon (IFN)‐α, IFN‐γ, interleukin (IL)‐6 cytokine storm, IL‐9 was raised in both mothers and neonates. Pyruvate, NAD metabolism and increase in IL‐9 and IFN‐γ had an impact on nonclassical monocytes, exhausted T and B cells. Our results demonstrated that immune‐metabolic interplay in mother and fetus is influenced with increase in IL‐9 and IFN‐γ regulated pyruvate, lactate tricarboxylic acid, and riboflavin metabolism with context to disease severity.
Fully automatic system to detect and segment the proximal femur in pelvic radiographic images for Legg–Calvé–Perthes disease
Authors: Ditmer Sofie , Dwenger Nicole , Jensen Louise N. , Kim Harry , Boel Rikke V. , Ghaffari Arash , Rahbek Ole 
Published: December 2023

AbstractThis study aimed to develop a method using computer vision techniques to accurately detect and delineate the proximal femur in radiographs of Legg–Calvé–Perthes disease (LCPD) patients. Currently, evaluating femoral head deformity, a crucial predictor of LCPD outcomes, relies on unreliable categorical and qualitative classifications. To address this limitation, we employed the pretrained object detection model YOLOv5 to detect the proximal femur on over 2000 radiographs, including images of shoulders and chests, to enhance robustness and generalizability. Subsequently, we utilized the U‐Net convolutional neural network architecture for image segmentation of the proximal femur in more than 800 manually annotated images of stage IV LCPD. The results demonstrate outstanding performance, with the object detection model achieving high accuracy (mean average precision of 0.99) and the segmentation model attaining an accuracy score of 91%, dice coefficient of 0.75, and binary IoU score of 0.85 on the held‐out test set. The proposed fully automatic proximal femur detection and segmentation system offers a promising approach to accurately detect and delineate the proximal femoral bone contour in radiographic images, which is essential for further image analysis in LCPD patients. Clinical significance: This study highlights the potential of computer vision techniques for enhancing the reliability of Legg–Calvé–Perthes disease staging and outcome prediction.
Lactational changes in Filipino human milk oligosaccharides reveal maternal secretor status
Authors: Albaladejo Anthony Salvador B. , Nacario Ruel C. , Navarro Baby Richard R. , Lebrilla Carlito B. , Completo Gladys C. 
Published: December 2023

AbstractBackgroundBreast milk contains human milk oligosaccharides (HMOs), which are the third most abundant solid component and are considered indigestible with no nutritional value to infants. However, HMOs provide protection against pathogens, support gut bacteria, and aid in brain development. This study investigated the relationship between HMOs and secretor status and tracked changes in HMO levels throughout lactation. The study employed a rapid‐throughput extraction method, nano‐HPLC Chip/TOF‐MS analysis, and an annotated HMO structure library for oligosaccharide analysis.ResultsResults from the study revealed that 81% of Filipino mothers (N = 155) are secretors, while 19% are non‐secretors. The total HMO abundance significantly decreased (p = 0.0001) throughout lactation but was significantly (p = 0.0390) higher in colostrum compared with mature milk. The total fucosylated HMOs had a significantly (p = 0.0460) lower absolute abundance, while the total sialylated HMOs showed a significantly (p = 0.0012) higher abundance in colostrum relative to mature milk. Non‐fucosylated neutral HMOs showed no significant (p = 0.1040) difference in abundance between colostrum and mature milk.ConclusionThis is the first comprehensive data on the maternal secretor status of Filipino mothers, showing the decrease in total HMO abundance throughout lactation and differences in the abundances of various oligosaccharide types between colostrum and mature milk.
Effects of rosmarinic acid on immune response and intestinal microbiota in ovalbumin‐induced intestinal allergy mice
Authors: Yang Qing , Jia Binmei , Shang Jieli , Wang Xuanpei , Xu Lin , Liu Xin , Fang Min , Zeng Fengbo , Zeng Hao‐Long , Gong Zhiyong 
Published: December 2023

AbstractBACKGROUNDRosmarinic acid (RA) is an active polyphenol that is widely found in various edible herbs. This study explored the potential anti‐allergic activities and the underlying mechanisms of RA in ovalbumin (OVA)‐induced intestinal allergic mice.RESULTSForty female BALB/c mice were randomly divided into five groups: control group, model group (OVA sensitized/challenged), RA‐Low group (OVA sensitized/challenged, 30 mg kg−1 RA intervention), RA‐Middle group (OVA sensitized/challenged, 90 mg kg−1 RA intervention) and RA‐High group (OVA sensitized/challenged, 270 mg kg−1 RA intervention). RA effectively attenuated allergic reactions, including alleviating allergic symptoms and regulating the hypothermia of mice in the model group. Moreover, the anaphylactic mediator (OVA‐specific IgE, histamine and mMCP‐1) levels of OVA allergic mice were markedly decreased after RA intervention. Quantitative polymerase chain reaction analysis showed that RA significantly inhibited Th2 cytokine expression, while Th1 and Treg cytokines were markedly increased. 16S rRNA gene sequence analysis indicated that RA effectively regulated the richness and diversity of the intestinal microbiota in OVA allergic mice. At the phylum level, the relative abundance of Bacteroidetes and Firmicutes and the Firmicutes/Bacteroidetes ratio were altered by RA intervention. At the genus level, RA was found to regulate the disturbances in the relative abundance of Muribaculaceae, Lactobacillus and Prevotella.CONCLUSIONRA exhibited potential anti‐allergic activity in OVA allergic mice by regulating hypersensitive immune responses and the intestinal microbiota structure. These results provide important evidence that RA can be developed into a novel functional food‐derived ingredient against food allergy. © 2023 Society of Chemical Industry.
A multidimensional evaluation of the effects of sweetener selection and UV‐C treatment on orange juice and pectin‐based confectionery gels
Authors: Andreone Antonella , Kozono María Luz , Schenk Marcela , Guerrero Sandra 
Published: December 2023

AbstractBACKGROUNDConsumers are seeking healthier alternatives to traditional confectioneries. They value the use of sugar replacers, more natural ingredients and/or environmentally friendly preservation technologies. UV‐C light is considered an emerging alternative to thermal pasteurization that leaves no residue and requires minimal energy. The present study aimed to investigate the effect of novel sweetener combinations and juice UV‐C assisted by mild heat treatment (UV‐C/H) on the physicochemical, microbiological, morphological, rheological and sensory properties of orange juice pectin‐based confectioneries stored at 5 ± 1 °C for 35 days.RESULTSFor orange juice processing, UV‐C/H (pilot‐scale Dean‐flow reactor; 892 mJ cm−2; 50 ± 1 °C) and thermal (T‐coil, 80 °C; 6 min) treatments were used. Low‐calorie confectionery gels were elaborated using the treated juices, low‐methoxyl pectin and various sweetener combinations. UV‐C/H and T‐coil effectively inactivated juice native microbiota. The proposed formulations, derived from a previous Box–Behnken optimization study, included partial (F1: 3%‐sucrose‐S + 0.019%‐rebaudioside‐A‐RA) or complete sucrose replacement (F2: 5.5%‐erythritol‐E + 0.019%‐RA), and one control (C:10%‐S). In general, the microbiota of the gels prepared with the UV‐C/H or T‐coil treated juices did not recover during storage. The physicochemical and mechanical parameters of the formulations were significantly influenced by the choice of sweetener and the duration of storage. The gel surface got smoother and had fewer holes when the sucrose level dropped, according to a scanning electron microscopy study. The UV‐C/H‐treated samples did not differ in acceptability, whereas the measured sensory attributes approached ideal levels. F1 and F2 showed distinctive temporal‐dominance‐of‐sensations profiles, mainly dominated by sweetness and orange taste, respectively. However, consumers perceived sourness and astringency in C during consumption.CONCLUSIONThe present study provides significant evidence in support of the development of confectionery gels F1 and F2 made from fruit juice treated by UV‐C light assisted by mild heat and combinations of sucrose‐alternative sweeteners. In terms of the properties investigated, these confectionery gels were comparable to, or even outperformed the full‐sucrose option. © 2023 Society of Chemical Industry.
Serum Neurofilament Light Chain in Replication Factor Complex Subunit 1 CANVAS and Disease Spectrum
Authors: Quartesan Ilaria , Vegezzi Elisa , Currò Riccardo , Heslegrave Amanda , Pisciotta Chiara , Iruzubieta Pablo , Salvalaggio Alessandro , Fernández‐Eulate Gorka , Dominik Natalia , Rugginini Bianca , Manini Arianna , Abati Elena , Facchini Stefano , Manso Katarina , Albajar Ines , Laban Rhiannon , Rossor Alexander M. , Pichiecchio Anna , Cosentino Giuseppe , Saveri Paola , Salsano Ettore , Andreetta Francesca , Valente Enza M. , Zetterberg Henrik , Giunti Paola , Stojkovic Tanya , Briani Chiara , López de Munain Adolfo , Pareyson Davide , Reilly Mary M. , Houlden Henry , Tassorelli Cristina , Cortese Andrea 
Published: December 2023

AbstractBackgroundBiallelic intronic AAGGG repeat expansions in the replication factor complex subunit 1 (RFC1) gene were identified as the leading cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome. Patients exhibit significant clinical heterogeneity and variable disease course, but no potential biomarker has been identified to date.ObjectivesIn this multicenter cross‐sectional study, we aimed to evaluate neurofilament light (NfL) chain serum levels in a cohort of RFC1 disease patients and to correlate NfL serum concentrations with clinical phenotype and disease severity.MethodsSixty‐one patients with genetically confirmed RFC1 disease and 48 healthy controls (HCs) were enrolled from six neurological centers. Serum NfL concentration was measured using the single molecule array assay technique.ResultsSerum NfL concentration was significantly higher in patients with RFC1 disease compared to age‐ and‐sex‐matched HCs (P < 0.0001). NfL level showed a moderate correlation with age in both HCs (r = 0.4353, P = 0.0020) and patients (r = 0.4092, P = 0.0011). Mean NfL concentration appeared to be significantly higher in patients with cerebellar involvement compared to patients without cerebellar dysfunction (27.88 vs. 21.84 pg/mL, P = 0.0081). The association between cerebellar involvement and NfL remained significant after controlling for age and sex (β = 0.260, P = 0.034).ConclusionsSerum NfL levels are significantly higher in patients with RFC1 disease compared to HCs and correlate with cerebellar involvement. Longitudinal studies are warranted to assess its change over time.
Cystic acne treatment: A comprehensive review
Authors: Durairaj Akiladevi , Elumalai Karthikeyan , Shanmugam Anandakumar 
Published: December 2023

AbstractAcne, a common skin condition, is primarily seen in teenagers and young adults and is characterised by large pus‐filled bumps beneath the skin. Cystic acne is a common form and is linked to a high incidence of acne‐related skin diseases. Causes include age, sex, and lifestyle changes. Treatment options for severe acne include medications, laser therapy, chemical peels, and microneedling patches. This review focuses on cystic acne treatment options and discusses their advantages and disadvantages. Medications like isotretinoin reduce inflammation but have side effects. Laser therapy targets bacteria without medication but may require multiple sessions for optimal results.
γ‐Oryzanol Ameliorates Depressive Behavior in Ovariectomized Mice by Regulating Hippocampal Nitric Oxide Synthase: A Potential Therapy for Menopausal Depression
Authors: Kim Minji , Yoon Minseok , Cho Suengmok , Lee Changho , Um Min Young 
Published: December 2023

ScopeDepression is a severe mental condition, common among menopausal women. γ‐Oryzanol (ORY) has various biological properties; however, the effect of ORY on menopausal depression and its underlying mechanisms have not been investigated.Methods and resultsORY is orally administered to ovariectomized (OVX) mice for 20 weeks. ORY administration results in lower immobility time in the tail suspension and forced swim test and increases locomotor activity in the open field test. In the primary hippocampal neurons and hippocampi of OVX mice, ORY treatment increases nitric oxide (NO) production and neuronal NO synthase (nNOS) expression. Further, the phosphorylation of extracellular signal‐regulated kinase (ERK), cAMP response element‐binding protein (CREB), and tropomyosin receptor kinase B, along with the expression of brain‐derived neurotrophic factior (BDNF), is upregulated. These stimulatory effects of ORY are diminished by treatment with estrogen receptor β (ERβ) antagonist. ORY similarly interacts with ERβ in the molecular docking analysis. Moreover, intracerebroventricular injection of 7‐nitroindazole, a nNOS inhibitor, abolishes the antidepressant effects of ORY.ConclusionsThe results indicate that ORY attenuates depressive behavior in OVX mice by upregulating ERβ‐mediated hippocampal nNOS expression and activating the ERK‐CREB‐BDNF signaling networks. The findings suggest that ORY is a potential therapeutic agent for attenuating menopausal depression.
AAPM Task Group Report 311: Guidance for performance evaluation of fluorescence‐guided surgery systems
Authors: Pogue Brian W. , Zhu Timothy C. , Ntziachristos Vasilis , Wilson Brian C. , Paulsen Keith D. , Gioux Sylvain , Nordstrom Robert , Pfefer T. Joshua , Tromberg Bruce J. , Wabnitz Heidrun , Yodh Arjun , Chen Yu , Litorja Maritoni 
Published: December 2023

AbstractThe last decade has seen a large growth in fluorescence‐guided surgery (FGS) imaging and interventions. With the increasing number of clinical specialties implementing FGS, the range of systems with radically different physical designs, image processing approaches, and performance requirements is expanding. This variety of systems makes it nearly impossible to specify uniform performance goals, yet at the same time, utilization of different devices in new clinical procedures and trials indicates some need for common knowledge bases and a quality assessment paradigm to ensure that effective translation and use occurs. It is feasible to identify key fundamental image quality characteristics and corresponding objective test methods that should be determined such that there are consistent conventions across a variety of FGS devices. This report outlines test methods, tissue simulating phantoms and suggested guidelines, as well as personnel needs and professional knowledge bases that can be established. This report frames the issues with guidance and feedback from related societies and agencies having vested interest in the outcome, coming from an independent scientific group formed from academics and international federal agencies for the establishment of these professional guidelines.