bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controlled release of resveratrol from a composite nanofibrous scaffold: Effect of resveratrol on antioxidant activity and osteogenic differentiation
Authors: Karimi‐Soflou Reza , Mohseni‐Vadeghani Elham , Karkhaneh Akbar 
Published: July 2021

AbstractBiocompatibility, mechanical strength, and osteogenesis properties of three‐dimensional scaffolds are critical for bone tissue engineering. In addition, reactive oxygen species accumulate around bone defects and limit the activities of surrounding cells and bone formation. Therefore, the presence of an antioxidant in a bone tissue scaffold is also essential to address this issue. This study aimed to evaluate a composite nanofibrous scaffold similar to the natural extracellular matrix with antioxidant and osteogenic properties. To this end, polylactic acid (PLA)/organophilic montmorillonite (OMMT)/resveratrol (RSV) nanofibers were fabricated using the electrospinning method and characterized. RSV was used as an antioxidant, which promotes osteogenic differentiation, and OMMT was used as a mineral phase to increase the mechanical strength and control the release of RSV. The scaffolds' antioxidant activity was measured using DPPH assay and found 83.75% for PLA/OMMT/RSV nanofibers. The mechanical strength was increased by adding OMMT to the neat PLA. The biocompatibility of the scaffolds was investigated using an MTT assay, and the results did not show any toxic effects on human adipose mesenchymal stem cells (hASCs). Moreover, the Live/Dead assay indicated the appropriate distribution of live cells after 5 days. Cell culture results displayed that hASCs could adhere and spread on the surface of composite nanofibers. Meanwhile, the level of alkaline phosphatase, osteocalcin, and osteopontin was increased for hASCs cultured on the PLA/OMMT/RSV nanofibrous scaffold. Therefore, this study concludes that the RSV‐loaded composite nanofibers with antioxidant and osteogenesis properties and appropriate mechanical strength can be introduced for bone tissue regeneration applications.
A comprehensive account of insulin and LDL receptor activity over the years: A highlight on their signaling and functional role
Authors: Chandra Nimai C. 
Published: July 2021

AbstractInsulin receptor (IR) was discovered in 1970. Shortcomings in IR transcribed signals were found pro‐diabetic, which could also inter‐relate obesity and atherosclerosis in a time‐dependent manner. Low‐density lipoprotein receptor (LDLR) was discovered in 1974. Later studies showed that insulin could modulate LDLR expression and activity. Repression of LDLR transcription in the absence or inactivity of insulin showed a direct cause of atherosclerosis. Leptin receptor (OB‐R) was found in 1995 and its resistance became responsible for developing obesity. The three interlinked pathologies namely, diabetes, atherosclerosis, and obesity were later on marked as metabolic syndrome‐X (MSX). In 2012, the IR–LDLR inter‐association was identified. In 2019, the proficiency of signal transmission from this IR–LDLR receptor complex was reported. LDLR was found to mimic IR‐generated signaling path when it remains bound to IR in IR–DLR interlocked state. This was the first time LDLR was found sending messages besides its LDL‐clearing activity from blood vessels.
Inhibition of NFAM1 suppresses phospho‐SAPK/JNK signaling during osteoclast differentiation and bone resorption
Authors: Ethiraj Purushoth , Haque Ishraq A. , Alford Anna K. , Gou Wenyu , Singh Toolika , Sambandam Yuvaraj , Hathaway‐Schrader Jessica D. , Reddy Sakamuri V. 
Published: July 2021

AbstractWe have recently demonstrated NFAT activating protein with ITAM motif 1 (NFAM1) signaling increases osteoclast (OCL) formation/bone resorption associated with the Paget's disease of bone, however, the underlying molecular mechanisms of the NFAM1 regulation of OCL differentiation and bone resorption remains unclear. Here, we showed that RANK ligand stimulation enhances NFAM1 expression in preosteoclast cells. Conditioned media collected from RANKL stimulated RAW264.7 NFAM1 knockdown (KD) stable cells showed inhibition of interleukin‐6 (2.5‐fold), tumour necrosis factor‐α (2.2‐fold) and CXCL‐5 (3‐fold) levels compared to wild‐type (WT) cells. Further, RANKL stimulation significantly increased p‐STAT6 expression (5.5‐fold) in WT cells, but no significant effect was observed in NFAM1‐KD cells. However, no changes were detected in signal transducer and activator of transcription 3 levels in either of cell groups. Interestingly, NFAM1‐KD suppressed the RANKL stimulated c‐fos, p‐c‐Jun and c‐Jun N‐terminal kinase (JNK) activity in preosteoclasts. We further showed that the suppression of JNK activity is through inhibition of p‐SAPK/JNK in these cells. In addition, NFATc1 expression, a critical transcription factor associated with osteoclastogenesis is significantly inhibited in NFAM1‐KD preosteoclast cells. Interestingly, NFAM1 inhibition suppressed the OCL differentiation and bone resorption capacity in mouse bone marrow cell cultures. We also demonstrated inhibition of tartrate‐resistant acid phosphatase expression in RANKL stimulated NFAM1‐KD preosteoclast cells. Thus, our results suggest that NFAM1 control SAPK/JNK signaling to modulate osteoclast differentiation and bone resorption.
Shake tube perfusion cell cultures are suitable tools for the prediction of limiting substrate, CSPR, bleeding strategy, growth and productivity behavior
Authors: Mayrhofer Patrick , Castan Andreas , Kunert Renate 
Published: July 2021

AbstractBACKGROUNDScale‐down models (SDM) are crucial for efficient setting of different experimental conditions in cell culture media‐ or clone‐screening applications and to predict the expected performance in larger bioreactor cultivations. However, the availability of such models for continuous bioprocessing are scarce and hampered by the requirement for proper cell retention in perfusion applications.RESULTSIn this study, perfusion scale‐down models were optimized for increased cell performance in shake tubes by a semi‐continuous operation mode without any instrumental monitoring. A 40 L perfusion bioreactor was simulated with 10 mL shake tubes by daily medium exchange with or without cell bleeding for process fine‐tuning. Specifically, the optimal cell‐specific perfusion rate (CSPR) was efficiently identified using the perfusion SDM. The cellular growth and productivity were nearly identical to those of the large‐scale experiments. The 24‐h interval of metabolite analysis identified the limits of the SDMs and underscores the need for perfusion processes in large‐scale animal cell bioprocesses.CONCLUSIONOptimized perfusion scale‐down models in semi‐continuous operation mode are highly suitable tools to define important process parameters of larger perfusion bioreactor cultures and are predictive of cellular growth and production behavior.
Detection of Prostate Cancer Using Biparametric Prostate MRI, Radiomics, and Kallikreins: A Retrospective Multicenter Study of Men With a Clinical Suspicion of Prostate Cancer
Authors: Montoya Perez Ileana , Merisaari Harri , Jambor Ivan , Ettala Otto , Taimen Pekka , Knaapila Juha , Kekki Henna , Khan Ferdhos L. , Syrjälä Elise , Steiner Aida , Syvänen Kari T. , Verho Janne , Seppänen Marjo , Rannikko Antti , Riikonen Jarno , Mirtti Tuomas , Lamminen Tarja , Saunavaara Jani , Falagario Ugo , Martini Alberto , Pahikkala Tapio , Pettersson Kim , Boström Peter J. , Aronen Hannu J. 
Published: July 2021

BackgroundAccurate detection of clinically significant prostate cancer (csPCa), Gleason Grade Group ≥ 2, remains a challenge. Prostate MRI radiomics and blood kallikreins have been proposed as tools to improve the performance of biparametric MRI (bpMRI).PurposeTo develop and validate radiomics and kallikrein models for the detection of csPCa.Study TypeRetrospective.PopulationA total of 543 men with a clinical suspicion of csPCa, 411 (76%, 411/543) had kallikreins available and 360 (88%, 360/411) did not take 5‐alpha‐reductase inhibitors. Two data splits into training, validation (split 1: single center, n = 72; split 2: random 50% of pooled datasets from all four centers), and testing (split 1: 4 centers, n = 288; split 2: remaining 50%) were evaluated.Field strength/SequenceA 3 T/1.5 T, TSE T2‐weighted imaging, 3x SE DWI.AssessmentIn total, 20,363 radiomic features calculated from manually delineated whole gland (WG) and bpMRI suspicion lesion masks were evaluated in addition to clinical parameters, prostate‐specific antigen, four kallikreins, MRI‐based qualitative (PI‐RADSv2.1/IMPROD bpMRI Likert) scores.Statistical TestsFor the detection of csPCa, area under receiver operating curve (AUC) was calculated using the DeLong's method. A multivariate analysis was conducted to determine the predictive power of combining variables. The values of P‐value < 0.05 were considered significant.ResultsThe highest prediction performance was achieved by IMPROD bpMRI Likert and PI‐RADSv2.1 score with AUC = 0.85 and 0.85 in split 1, 0.85 and 0.83 in split 2, respectively. bpMRI WG and/or kallikreins demonstrated AUCs ranging from 0.62 to 0.73 in split 1 and from 0.68 to 0.76 in split 2. AUC of bpMRI lesion‐derived radiomics model was not statistically different to IMPROD bpMRI Likert score (split 1: AUC = 0.83, P‐value = 0.306; split 2: AUC = 0.83, P‐value = 0.488).Data ConclusionThe use of radiomics and kallikreins failed to outperform PI‐RADSv2.1/IMPROD bpMRI Likert and their combination did not lead to further performance gains.Level of Evidence1Technical EfficacyStage 2
Clinical features and outcome of COVID‐19 positive children from a tertiary healthcare hospital in Karachi
Authors: Shahid Saba , Raza Mohammad , Junejo Samina , Maqsood Sidra 
Published: July 2021

Abstract As the coronavirus disease 2019 (COVID‐19) pandemic continues to evolve, differences in epidemiological and clinical features among pediatrics have been noticed across different countries. We describe the spectrum of COVID‐19 in pediatric patients treated in tertiary health care. We conducted a retrospective chart review of pediatric patients admitted to Indus Hospital & Health care network, Korangi campus, Karachi; from April 1st, 2020 to July 31st, 2020. A total of 141 COVID‐19 cases were reported, males were 81 (57%) and the median age was 8 (0.3–17) years. Moderate and severe infections were noted in 36(26%), and 17(12%) children respectively. Fever (50%) was the most common clinical feature. The SF ratio less than 264 was significantly associated with severe disease (p < .05). Lab investigations that differed significantly across disease severity groups included IL‐6 levels (p < .01) and Prothrombin time (p < .05). Majority of children were advised home isolation 89 (63%), 29 (20.5%) were admitted while mortality was observed in 10 (7%) children. No significant difference was observed between children with and without malignancy. Pre‐existing comorbidities are significantly associated with COVID‐19 infections among children. Reduced SF ratio, elevated Prothrombin time, and interleukin‐6 levels are associated with greater disease severity.
Rhinovirus spread in children during the COVID‐19 pandemic despite social restrictions—A nationwide register study in Finland
Authors: Kuitunen Ilari , Artama Miia , Haapanen Marjut , Renko Marjo 
Published: July 2021

AbstractSocial restrictions during the coronavirus disease 2019 pandemic strongly affected the epidemiology of influenza and respiratory syncytial virus (RSV). As rhinovirus seemed to spread despite the restrictions, we aimed to analyze rhinovirus epidemiology in children during the pandemic. This register‐based study used data from the Finnish Infectious Disease Register. Nationwide rhinovirus findings from July 2015 to March 2021 were included and stratified by age (0–4, 5–9, and 10–14). Cumulative 14‐day incidence per 100000 children was calculated. Four thousand five hundred and seventy six positive rhinovirus findings were included, of which 3788 (82.8%) were among children aged 0–4. The highest recorded incidence was 36.2 among children aged 0–4 in October 2017. The highest recorded incidence during the pandemic period was 13.6 in November 2020. The impact of the restrictions was mostly seen among children aged 0–4 years of age in weeks 14–22 in 2020. The incidence has since remained near reference levels in all age groups. Strict restrictions temporarily interrupted the circulation of rhinovirus in spring 2020. Rhinovirus incidence returned to normal levels soon after the harsh restrictions were lifted. These looser social restrictions prevented RSV and influenza seasons but failed to prevent the spread of rhinovirus.
Biological and chemical characterization of antimicrobial activity in Arthrobacter spp. isolated from disease‐suppressive compost
Authors: Ramlawi Serine , Abusharkh Sawsan , Carroll Alexa , McMullin David R. , Avis Tyler J. 
Published: July 2021

AbstractAntagonistic bacteria can act as biocontrol agents against various phytopathogens. Recently, Arthrobacter spp. demonstrated antifungal activity, but were not further characterized. In this study, the antimicrobial activity of Arthrobacter humicola strains M9‐1A, M9‐2, and M9‐8, and Arthrobacter psychrophenolicus strain M9‐17 were evaluated against nine plant pathogens in vitro, and their cell‐free filtrates were additionally assessed for inhibition of Alternaria alternata and suppression of black mold disease on tomato fruit. Results indicated that A. humicola M9‐1A and A. psychrophenolicus M9‐17 were the most inhibitory, reducing growth of seven of the pathogens studied. Cell‐free filtrates of A. psychrophenolicus M9‐17 reduced the growth of most pathogens. All cell‐free bacterial filtrates, except those from A. humicola M9‐2, suppressed black mold on tomato fruit. Disk diffusion assays with ethyl acetate soluble culture filtrate extracts of all bacteria reduced the mycelial growth of A. alternata. Clear inhibition zones were observed for A. psychrophenolicus M9‐17 extracts using drop bioassays. The antifungal compound N‐acetyltryptamine was purified and characterized from the A. psychrophenolicus M9‐17 cell‐free ethyl acetate soluble extract. This study suggests that antibiosis may play a key role in the antimicrobial activity of Arthrobacter spp.
Identification of sustainable trypsin active‐site inhibitors from Nigrospora sphaerica strain AVA‐1
Authors: Kallingal Anoop , Thachan Kundil Varun , Ayyolath Aravind , Muringayil Joseph Tomy , Kar Mahapatra Debarshi , Haponiuk Józef T. , Variyar E. Jayadevi 
Published: July 2021

AbstractTrypsin is a protein‐digesting enzyme that is essential for the growth and regeneration of bone, muscle, cartilage, skin, and blood. The trypsin inhibitors have various role in diseases such as inflammation, Alzheimer's disease, pancreatitis, rheumatoid arthritis, cancer prognosis, metastasis and so forth. From 10 endophytic fungi isolated, we were able to screen only one strain with the required activity. The fungus with activity was obtained as an endophyte from Dendrophthoe falcata and was later identified as Nigrospora sphaerica. The activity was checked by enzyme assays using trypsin. The fungus was fermented and the metabolites were extracted and further purified by bioassay‐guided chromatographic methods and the compound isolated was identified using gas chromatography–mass spectrometry. The compound was identified as quercetin. Docking studies were employed to study the interaction. The absorption, distribution, metabolism, and excretion analysis showed satisfactory results and the compound has no AMES and hepatotoxicity. This study reveals the ability of N. sphaerica to produce bioactive compound quercetin has been identified as a potential candidate for trypsin inhibition. The present communication describes the first report claiming that N. sphaerica strain AVA‐1 can produce quercetin and it can be considered as a sustainable source of trypsin active‐site inhibitors.
Oleanolic acid reshapes the gut microbiota and alters immune‐related gene expression of intestinal epithelial cells
Authors: Xue Chenyu , Lv Hao , Li Ying , Dong Na , Wang Yanhui , Zhou Jiale , Shi Baoming , Shan Anshan 
Published: July 2021

AbstractBACKGROUNDOleanolic acid (OA) is a pentacyclic triterpenoid compound that is present at high levels in olive oil and has several promising pharmacological effects, such as liver protection and anti‐inflammatory, antioxidant, and anticancer effects. The purpose of the present study was to assess whether OA treatment affects gut health compared to a control condition, including gut microbiota and intestinal epithelial immunity.RESULTSIllumina MiSeq sequencing (16S rRNA gene) was used to investigate the effect of OA on the microbial community of the intestinal tract, while Illumina HiSeq (RNA‐seq) technology was used to investigate the regulatory effect of OA on gene expression in intestinal epithelial cells, which allowed for a comprehensive analysis of the effects of OA on intestinal health. The results showed that the consumption of OA initially controlled weight gain in mice and altered the composition of the gut microbiota. At the phylum level, OA significantly increased the relative abundances of cecum Firmicutes but decreased the abundance of Actinobacteria, and at the genus level it increased the relative abundance of potentially beneficial bacteria such as Oscillibacter and Ruminiclostridium 9. Oleanolic acid treatment also altered the expression of 12 genes involved in the Kyoto Encyclopedia of Genes and Genomes（KEGG）pathways of complement and coagulation cascades, hematopoietic cell lineage, and leukocyte transendothelial migration in intestinal epithelial cells to improve gut immunity.CONCLUSIONIntake of OA can contribute beneficial effects by optimizing gut microbiota and altering the immune function of intestinal epithelial cells, potentially to improve intestinal health status. © 2021 Society of Chemical Industry.
Free vascularized iliac periosteal graft for bilateral forearm nonunion reconstruction in a child with bilateral transfemoral amputation
Authors: Soldado Francisco , Barrera‐Ochoa Sergi , Campillo‐Recio David , Nguyen‐Saint‐Paul Quynh , Cherqaoui Abdelmounim , Knörr Jorge 
Published: July 2021

AbstractVascularized periosteal flaps have been reported as very effective for treating biologically complex bone nonunion in pediatric patients, owing to their high angiogenic and osteogenic potentials. The purpose of this article is to report a case of a 6‐year‐old patient with nonunion involving both forearms and a very limited bone flap donor site in the context of prior bilateral transfemoral amputation due to meningococcal sepsis. Two free vascularized iliac periosteal flaps (VIPF), supplied by the deep circumflex iliac vessels, were used in two stages to reconstruct the forearms. In the first stage, the left forearm, which had a diaphyseal bone defect of 5 cm diameter in the ulna and 4 cm in the radius, was combined with an iliac‐crest bone allograft, fixed with two longitudinal 1.8 mm Kirschner wires and surrounded with a free VIPF of 24 cm2. Consolidation was achieved 3 months after left forearm surgery, while complete allograft revascularization and remodeling was observed at 12 months. In the second stage, the right forearm, which had a diaphyseal bone defect of 3 cm diameter in the ulna and 1 cm in the radius, was fixed the radius with a 2.7 mm plate and surrounded with a free VIPF of 24 cm2. The radius nonunion healed 6 weeks after surgery. There were no postoperative complications. Two years postoperatively, the patient had again resumed his arm gait painlessly and without a splint. VIPF may be considered a valuable and reliable surgical option for nonunion reconstruction in complex clinical scenarios in children.
Oromandibular reconstruction with double‐skin paddle fibular free flap: A systematic review and meta‐analysis
Authors: Lucattelli Elena , Brogi Mattia , Cipriani Federico , Innocenti Marco , Cannamela Giacomo , Innocenti Alessandro 
Published: July 2021

AbstractBackgroundReconstruction of complex head and neck defects is challenging, especially when more than one soft‐tissue subunit is involved. The osteocutaneous fibular flap underwent continual evolution to improve its soft‐tissue characteristics, such as including a second skin island. The purpose of this study was to evaluate outcomes regarding oromandibular reconstruction with a double‐skin paddle fibular free flap (DSPFFF) using three different techniques: central de‐epithelialized skin paddle, distally‐based double‐skin paddle (DSP), or proximally and distally‐based DSP.MethodsA systematic review was performed in December 2020 using Pubmed and MedLine Ovid databases according to the PRISMA guidelines. A meta‐analysis of functional outcome and complications was performed to estimate single incidence rates.ResultsA total of 449 patients were included, with a follow‐up of 1–84 months, where 330 patients underwent reconstruction with the first technique, 23 patients with the second technique, and 96 patients with the third technique. The meta‐analysis showed an overall good functional outcome and a low‐complication rate for oromandibular reconstruction with DSPFFF. A better functional outcome and a lower complication rate were found when a distally‐based DSPFFF was harvested compared to a proximally and distally‐based DSPFFF.ConclusionThe DSPFFF was found to be useful and reliable for reconstructing composite and extensive head and neck defects, with an overall good functional outcome and a low‐complication rate. The meta‐analysis showed a better positive outcome on distally‐based DSPFFF rather than proximally and distally‐based DSPFFF. In addition, distally‐based DSPFFF showed a lower complications rate when compared with proximally and distally‐based DSPFFF.
Comprehensive Human Milk Patterns Are Related to Infant Growth and Allergy in the CHMP Study
Authors: Jiang Shilong , Pan Jiancun , Li Yuanyuan , Ju Mengnan , Zhang Wei , Lu Jing , Lv Jiaping , Li Kaifeng 
Published: July 2021

ScopeThe aim of the present study is to identify human milk pattern using multi‐omics datasets and to explore association between patterns, infant growth, and allergy using data from the Chinese Human Milk Project (CHMP) study.Methods and ResultsThree patterns are identified from integrative analysis of proteome, lipidome, and glycome profiles of 143 mature human milk samples. Factor 1 is positively associated with 128 proteins, phospholipids, and human milk oligosaccharides (HMOs) including lacto N‐neohexaose (LNnH) and lacto‐N‐difucohexaose II (LNDFH II); factor 2 is negatively associated with as1‐casein, phospholipids while positively associates with HMOs including LNnH, lactosialyl tetrasaccharide c (LSTc), and 2’‐fucosyllactose (2'FL); factor 3 is positively associated with lysophospholipids while negatively associates with 27 proteins, triglycerides with two saturated fatty acids, 6'‐sialyllactose (6'SL) and 2'FL. In general, factor 1 and factor 2 are associated with slower while factor 3 is associated with faster growth rate (p < 0.044). One unit higher in loadings of factor 2 is associated with 34% lower risk of allergies (p ≤ 0.017). Associations are not significant after adjustment for city except for factor 1.ConclusionsThree possible human milk patterns with varying degree of stability are identified. Future work is needed to understand these patterns in terms of generalization, biologic mechanisms, and genotype influences.