bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Prognostic Factors and Molecular Subtypes of Breast Cancer With a Continuous‐Time Random‐Walk MR Diffusion Model: Using Whole Tumor Histogram Analysis
Authors: Qin Yanjin , Tang Caili , Hu Qilan , Yi Jingru , Yin Ting , Ai Tao 
Published: October 2022

BackgroundThe continuous‐time random‐walk (CTRW) diffusion model to evaluate breast cancer prognosis is rarely reported.PurposeTo investigate the correlations between apparent diffusion coefficient (ADC) and CTRW‐specific parameters with prognostic factors and molecular subtypes of breast cancer.Study TypeRetrospective.PopulationOne hundred fifty‐seven women (median age, 50 years; range, 26–81 years) with histopathology‐confirmed breast cancer.Field Strength/SequenceSimultaneous multi‐slice readout‐segmented echo‐planar imaging at 3.0T.AssessmentThe histogram metrics of ADC, anomalous diffusion coefficient (D), temporal diffusion heterogeneity (α), and spatial diffusion heterogeneity (β) were calculated for whole‐tumor volume. Associations between histogram metrics and prognostic factors (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2], and Ki‐67 proliferation index), axillary lymph node metastasis (ALNM), and tumor grade were assessed. The performance of histogram metrics, both alone and in combination, for differentiating molecular subtypes (HER2‐positive, Luminal or triple negative) was also assessed.Statistical TestsComparisons were made using Mann–Whitney test between different prognostic factor statuses and molecular subtypes. Receiver operating characteristic curve analysis was used to assess the performance of mean and median histogram metrics in differentiating the molecular subtypes. A P value <0.05 was considered statistically significant.ResultsThe histogram metrics of ADC, D, and α differed significantly between ER‐positive and ER‐negative status, and between PR‐positive and PR‐negative status. The histogram metrics of ADC, D, α, and β were also significantly different between the HER2‐positive and HER2‐negative subgroups, and between ALNM‐positive and ALNM‐negative subgroups. The histogram metrics of α and β significantly differed between high and low Ki‐67 proliferation subgroups, and between histological grade subgroups. The combination of αmean and βmean achieved the highest performance (AUC = 0.702) to discriminate the Luminal and HER2‐positive subtypes.Data ConclusionWhole‐tumor histogram analysis of the CTRW model has potential to provide additional information on the prognosis and intrinsic subtyping classification of breast cancer.Evidence Level4Technical EfficacyStage 2
Comparison of nucleocapsid and spike antibody ELISAs for determining SARS‐CoV‐2 seropositivity in Kenyan women and infants
Authors: Fish Carolyn S. , Owiti Prestone , Begnel Emily R. , Itell Hannah L. , Ojee Ednah , Adhiambo Judith , Ogweno Vincent , Holland LaRinda A. , Richardson Barbra A. , Khan Adam K. , Maqsood Rabia , Gantt Soren , Lim Efrem S. , Slyker Jennifer , Kinuthia John , Overbaugh Julie , Wamalwa Dalton , Lehman Dara A. , Chohan Bhavna H. 
Published: October 2022

AbstractA multitude of enzyme‐linked immunosorbent assays (ELISAs) has been developed to detect severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antibodies since the coronavirus disease 2019 pandemic started in late 2019. Assessing the reliability of these assays in diverse global populations is critical. This study compares the use of the commercially available Platelia Total Ab Assay (Bio‐Rad) nucleocapsid ELISA to the widely used Mount Sinai spike IgG ELISA in a Kenyan population seroprevalence study. Using longitudinal plasma specimens collected from a mother–infant cohort living in Nairobi, Kenya between May 2019 and December 2020, this study demonstrates that the two assays have a high qualitative agreement (92.7%) and strong correlation of antibody levels (R2 = 0.973) in repeated measures. Within this cohort, seroprevalence detected by either ELISA closely resembled previously published seroprevalence estimates for Kenya during the sampling period and no significant difference in the incidence of SARS‐CoV‐2 antibody detection by either assay was observed. Assay comparability was not affected by HIV exposure status. These data support the use of the Platelia SARS‐CoV‐2 Total Ab ELISA as a suitable high‐throughput method for seroprevalence studies in Kenya.
Small molecule RAF265 as an antiviral therapy acts against HSV‐1 by regulating cytoskeleton rearrangement and cellular translation machinery
Authors: Li Cui‐Cui , Chi Xiao‐Jing , Wang Jing , Potter Alexandra L , Wang Xiao‐Jia , Yang Chi‐Fu Jeffrey 
Published: October 2022

AbstractHost‐targeting antivirals (HTAs) have received increasing attention for their potential as broad‐spectrum antivirals that pose relatively low risk of developing drug resistance. The repurposing of pharmaceutical drugs for use as antivirals is emerging as a cost‐ and time‐ efficient approach to developing HTAs for the treatment of a variety of viral infections. In this study, we used a virus titer method to screen 30 small molecules for antiviral activity against Herpes simplex virus‐1 (HSV‐1). We found that the small molecule RAF265, an anticancer drug that has been shown to be a potent inhibitor of B‐RAF V600E, reduced viral loads of HSV‐1 by 4 orders of magnitude in Vero cells and reduced virus proliferation in vivo. RAF265 mediated cytoskeleton rearrangement and targeted the host cell's translation machinery, which suggests that the antiviral activity of RAF265 may be attributed to a dual inhibition strategy. This study offers a starting point for further advances toward clinical development of antivirals against HSV‐1.
Establishment of an indirect ELISA method for antibody detection of porcine pseudorabies by recombinant gB, gC, and gD proteins
Authors: Wu Xuemin , Chen Rujing , Chen Qiuyong , Che Yongliang , Yan Shan , Zhou Lunjiang , Wang Longbai 
Published: October 2022

AbstractPseudorabies virus (PRV), as a neuroherpes virus, leads to heavy economic losses in the pig industry worldwide. This study was designed to establish recombinant PRV glycoprotein B (gB), C, and D proteins as PRV diagnostic antigens. The gB/C, gC/D, and gB/C/D fusion sequences were synthesized and inserted into pET‐28a+ vector to generate the recombinant plasmids. The identified positive recombinant plasmids were transformed into BL21 Escherichia coli. The results of the polymerase chain reaction and enzyme digestion showed that the gB/C, gC/D, and gB/C/D fusion proteins were successfully expressed. An indirect sandwich ELISA was developed with the gB/C, gC/D, and gB/C/D as coating antigens. The results of indirect enzyme‐linked immunosorbent assay (ELISA) analysis of 184 PRV‐positive porcine sera showed that the positive coincidence rates of three recombinant proteins ELISAs relative to IDEXX kit were 98.25%, 95.32%, and 98.83%, and the negative coincidence rates were 85.71%, 75% and 100%, respectively. The inter and intra batch repeatability tests showed that the coefficient of variations of our kits were all less than 5%. Especially, the gB/C/D‐ELISA has the highest specificity and sensitivity among the ELISA methods developed in this study. We established a series expression system of gB/C, gC/D, and gB/C/D antigen epitope genes and Recombinant protein‐based indirect ELISA, providing new ideas for PV diagnosis and vaccine development.
Spatial and temporal characteristics of various cold surges over China during 1962–2018
Authors: Ma Li , Wei Zhigang , Li Xianru 
Published: October 2022

AbstractThe cold surge (CS) is an extreme climate event that frequently affects China. By using a 0.25° × 0.25° gridded observation dataset provided by the China Meteorological Administration (CN05.1), this paper investigates the spatial–temporal characteristics of various CSs in China during 1962–2018. According to the duration and coverage area (CA), CSs are classified into the short‐lived cold surges (SLCSs), the persistent cold surges (PCSs) and the extensive and persistent cold surges (EPCSs). They are also divided into the weak cold surges (WCSs), the strong cold surges (SCSs) and the super strong cold surges (SSCSs) based on the temperature drop (ΔT). The extreme cold surges (ECSs) are also defined and occur 38 times over 57 years. The total CSs and various CSs all display patterns of higher frequencies in the northeast and lower frequencies in the southwest. Northeast China and Inner Mongolia are frequently hit by various CSs, but the frequencies show overall downward trends in the regions during 1962–2018. The ΔT of the total CSs and ECSs both show significant decreasing trends in the whole of China from 1962 to 2018. From 1962 to 2018, the annual frequency and the ΔT of the total CSs both show decreasing trends. SLCSs and WCSs frequencies show overall increasing trends, but other kinds of CSs show overall decreasing trends. The annual frequencies of the total CSs and various CSs all have trend abrupt changes around 2000. The ΔT of ECSs shows a sharply increasing trend during 1962–2018. The total CSs and all kinds of CSs frequencies have a significant periodic oscillation. ECSs occur most in February. The total CSs and other kinds of CSs occur most in January. There are obvious differences between the multiyear average ECSs frequencies before 2000 and after 2000.
Single‐cell RNAseq provides insight into altered immune cell populations in human fracture nonunions
Authors: Avin Keith G. , Dominguez James M. , Chen Neal X. , Hato Takashi , Myslinski Jered J. , Gao Hongyu , Liu Yunlong , McKinley Todd O. , Brown Krista M. , Moe Sharon M. , Natoli Roman M. 
Published: October 2022

AbstractNonunion describes bone fractures that fail to heal, resulting in the fracture callus failing to fully ossify or, in atrophic cases, not forming altogether. Fracture healing is regulated, in part, by the balance of proinflammatory and anti‐inflammatory processes occurring within the bone marrow and surface cell populations. We sought to further understand the role of osteoimmunology (i.e., study of the close relationship between the immune system and bone) by examining immune cell gene expression via single‐cell RNA sequencing of intramedullary canal tissue obtained from human patients with femoral nonunions. Intramedullary canal tissue samples obtained by reaming were collected at the time of surgical repair for femur fracture nonunion (n = 5) or from native bone controls when harvesting autologous bone graft (n = 4). Cells within the samples were isolated and analyzed using the Chromium Single‐Cell System (10x Genomics Inc.) and Illumina sequencers. Twenty‐three distinct cell clusters were identified, with higher cell proportions in the nonunion samples for monocytes and CD14 + dendritic cells (DCs), and lower proportions of T cells, myelocytes, and promyelocytes in nonunion samples. Gene expression differences were identified in each of the cell clusters from cell types associated with osteoimmunology, including CD14 + DC, monocytes, T cells, promyelocytes, and myelocytes. These results provide human‐derived gene profiles that can further our understanding of pathways that may be a cause or a consequence of nonunion, providing the clinical rationale to focus on specific components of osteoimmunology. Clinical significance: The novel single‐cell approach may lead to clinically relevant diagnostic biomarkers during earlier stages of nonunion development and/or investigation into therapeutic options.
Platelet‐rich plasma versus corticosteroid injections in the management of patients with rotator cuff disease: A systematic review and meta‐analysis
Authors: Adra Maamoun , El Ghazal Nour , Nakanishi Hayato , Smayra Karen , Hong Sam S. , Miangul Shahid , Matar Reem H. , Than Christian A. , Tennent Duncan 
Published: October 2022

AbstractPlatelet‐rich plasma (PRP) is an alternative to corticosteroid (CS) injections in managing rotator cuff disease. This meta‐analysis investigated differences between PRP and CS for function and pain scores in significance and minimal clinical important difference (MCID). A literature search of Ovid Cochrane Library, Medline, Embase, Epub, and Scopus was conducted from inception to October 28, 2021. Eligible studies reported patients older than 18 years with a diagnosis of rotator cuff disease. This review was registered in PROSPERO (ID: CRD42021278740). Twelve studies met eligibility criteria (n = 639) of patients receiving either PRP or CS. At short‐term follow‐up, a difference favored CS compared to PRP in baseline change for disability of arm, shoulder, and hand (DASH) score (MD = −5.08, 95% CI: −8.00, −2.15; p = 0.0007; I2 = 0%) and simple shoulder test (SST) (MD = 1.25, 95% CI: 0.33, 2.18; p = 0.008; I2 = 0%). At intermediate follow‐up, a difference favored PRP to CS baseline change of the DASH score (MD = 3.41, 95% CI: 0.67, 6.15; p = 0.01; I2 = 0%). At medium‐term, a difference favored PRP to CS baseline change of the American Shoulder and Elbow Surgeons Shoulder (ASES) score (MD = −4.42, 95% CI: −8.16, −0.67; p = 0.02; I2 = 0%). Both treatments achieved individual MCID for each score. Despite favoring CS at short‐term follow‐up and PRP at intermediate‐ and medium‐term follow‐up, functional and pain scores did not demonstrate any clinical difference between the two treatment modalities in management of rotator cuff disease at all follow‐up periods.
Mechanical strain drives exosome production, function, and miRNA cargo in C2C12 muscle progenitor cells
Authors: Mullen Michael , Williams Katherine , LaRocca Tom , Duke Victoria , Hambright William S. , Ravuri Sudheer K. , Bahney Chelsea S. , Ehrhart Nicole , Huard Johnny 
Published: October 2022

AbstractMesenchymal stem cells (MSCs) have been proven to promote tissue repair. However, concerns related to their clinical application and regulatory hurdles remain. Recent data has demonstrated the proregenerative secretome of MSCs can result in similar effects in the absence of the cells themselves. Within the secretome, exosomes have emerged as a promising regenerative component. Exosomes, which are nanosized lipid vesicles secreted by cells, encapsulate micro‐RNA (miRNA), RNA, and proteins that drive MSCs regenerative potential with cell specific content. As such, there is an opportunity to optimize the regenerative potential of MSCs, and thus their secreted exosome fraction, to improve clinical efficacy. Exercise is one factor that has been shown to improve muscle progenitor cell function and regenerative potential. However, the effect of exercise on MSC exosome content and function is still unclear. To address this, we used an in vitro culture system to evaluate the effects of mechanical strain, an exercise mimetic, on C2C12 (muscle progenitor cell) exosome production and proregenerative function. Our results indicate that the total exosome production is increased by mechanical strain and can be regulated with different tensile loading regimens. Furthermore, we found that exosomes from mechanically stimulated cells increase proliferation and myogenic differentiation of naïve C2C12 cells. Lastly, we show that exosomal miRNA cargo is differentially expressed following strain. Gene ontology mapping suggests positive regulation of bone morphogenetic protein signaling, regulation of actin‐filament‐based processes, and muscle cell apoptosis may be at least partially responsible for the proregenerative effects of exosomes from mechanically stimulated C2C12 muscle progenitor cells.
Impact of Bifidobacterium animalis subsp. lactis HN019 probiotic in the prevention of periodontitis associated with immunosuppression
Authors: Maia Luciana Prado , de Almeida Silva Levi Yara Loyanne , Henrique Félix Silva Pedro , Carla Wons Luana , Pizzo Pitelli Livia , Goulart de Castro Jéssica , da Silva Dólens Eder , Gregorio Danielle , Gouveia Straioto Fabiana , dos Santos Santinoni Carolina , Casarin Renato , Ervolino Edilson , Aparecida Chaves Furlaneto Flávia , Reis Messora Michel 
Published: October 2022

AbstractBackgroundThis study evaluated the effects of the probiotic Bifidobacterium animalis subsp. lactis HN019 (HN019) in the development of experimental periodontitis (EP) in rats submitted to chemotherapy (5‐fluorouracil [5FU]).MethodsEighty male rats were divided into the following groups: control (C); treated with 5FU (60 mg/kg at day 30 and 40 mg/kg at day 32); treated with probiotic (HN019) (daily, for 44 days, starting at day 0); treatment with 5FU and probiotic (5FU‐HN019); only EP (EP) (ligature placed on lower first molars at day 30, maintained for 14 days); EP and treatment with 5FU (EP‐5FU); EP and treatment with probiotic (EP‐HN019); and EP and treatment with 5FU and probiotic (EP‐5FU‐HN019). Euthanasia occurred at day 44. Morphometric, histomorphometric, microtomographic, immunohistochemical, immunoenzymatic, and gene expressions analyses were performed. The data obtained were statistically analyzed (p < 0.05).ResultsThe EP‐5FU‐HN019 group showed less bone and connective tissue loss when compared with EP‐5FU group, while EP‐HN019 and EP‐5FU‐HN019 groups had greater bone volume than EP and EP‐5FU groups, respectively (p < 0.05). A decrease in immunostaining for tartrate‐resistant acid phosphatase and RANKL, an increase for osteoprotegerin and lower interleukin‐1β levels were observed in EP‐5FU‐HN019 group, when compared with EP‐5FU group (p < 0.0001). Probiotic therapy led to an increase in the proportions of B. lactis in the feces (p = 0.0018), but not in the biofilm, and reduced the expression of Fusobacterium nucleatum and Prevotella intermedia in the biofilm (p < 0.0001).ConclusionB. lactis HN019 reduced the severity of EP in rats submitted to chemotherapy, modulating immunoinflammatory parameters in periodontal tissues and reducing periodontopathogens expression on biofilm in rats submitted to chemotherapy.
Storage impact on egg white powder's physical and functional properties
Authors: Zhang Ting , Tang Yuanhu , Ge Huifang , Zhang Deju , Li Ting , Cheng Dongkun , Liu Jingbo , Yu Yiding 
Published: October 2022

AbstractBACKGROUNDChanges in storage temperature and time alter the functional properties of egg white powder (EWP) and determine its quality and shelf‐life, finally affecting the consumer acceptance of the products made from EWP. In the present study, the EWP samples were stored at four different temperatures (−20, 4, 25 and 37 °C) for 60 days, and then the protein structural, physical and functional properties of EWP were measured and assessed further for correlation with storage conditions using heatmap.RESULTSThe viscosity of the EWP solution increased after 30 days. Foaming ability and rheological properties increased first and then decreased compared to untreated samples with the prolonged storage time. Correlation analysis results indicated that the gel hardness, water holding capacity, foaming ability, emulsifying ability, particle size, dispersibility and viscosity of EWP were significantly related to storage time (P < 0.05). Only the gelation properties of EWP stored at 37 °C for 60 days changed significantly and were negatively related to its moisture content (P < 0.05). Additionally, the random coil content of EWP was positively correlated with particle size, moisture content, solubility and gel properties, whereas β‐sheet was negatively correlated with them.CONCLUSIONCompared to other temperatures, the functional properties of EWP were relatively stable under 4 °C. Therefore, the low temperature (4 °C) was selected as the most suitable storage temperature for EWP. The results of the present study could provide a theoretical basis for the shelf‐life extension of EWP. © 2022 Society of Chemical Industry.
Deep learning image analysis quantifies tumor heterogeneity and identifies microsatellite instability in colon cancer
Authors: Rubinstein Jill C. , Foroughi Pour Ali , Zhou Jie , Sheridan Todd B. , White Brian S. , Chuang Jeffrey H. 
Published: October 2022

AbstractBackground and ObjectivesDeep learning utilizing convolutional neural networks (CNNs) applied to hematoxylin & eosin (H&E)‐stained slides numerically encodes histomorphological tumor features. Tumor heterogeneity is an emerging biomarker in colon cancer that is, captured by these features, whereas microsatellite instability (MSI) is an established biomarker traditionally assessed by immunohistochemistry or polymerase chain reaction.MethodsH&E‐stained slides from The Cancer Genome Atlas (TCGA) colon cohort are passed through the CNN. Resulting imaging features are used to cluster morphologically similar slide regions. Tile‐level pairwise similarities are calculated and used to generate a tumor heterogeneity score (THS). Patient‐level THS is then correlated with TCGA‐reported biomarkers, including MSI‐status.ResultsH&E‐stained images from 313 patients generated 534 771 tiles. Deep learning automatically identified and annotated cells by type and clustered morphologically similar slide regions. MSI‐high tumors demonstrated significantly higher THS than MSS/MSI‐low (p < 0.001). THS was higher in MLH1‐silent versus non‐silent tumors (p < 0.001). The sequencing derived MSIsensor score also correlated with THS (r = 0.51, p < 0.0001).ConclusionsDeep learning provides spatially resolved visualization of imaging‐derived biomarkers and automated quantification of tumor heterogeneity. Our novel THS correlates with MSI‐status, indicating that with expanded training sets, translational tools could be developed that predict MSI‐status using H&E‐stained images alone.
Can low‐grade chondrosarcoma in flat bones be treated with intralesional curettage and cryotherapy?
Authors: Park Kwangwon , Krumme John , Adebayo Moses , Adams Brock W. , Henshaw Robert M. 
Published: October 2022

AbstractBackground and objectivesChondrosarcomas in flat bones are thought to be more aggressive in their behavior, and little is known about intralesional treatment outcomes of low‐grade chondrosarcoma in these locations. We tried to find the differences between patients who had low‐grade chondrosarcoma in their flat bones versus those with long bone involvement with regard to (1) disease outcome, (2) functional outcome, and (3) treatment complications.MethodsWe retrospectively reviewed 44 patients with primary low‐grade chondrosarcoma who were treated with intralesional curettage and cryotherapy. The patients were divided by location of tumor, group I (flat bones, seven patients) and group II (long bones, 37 patients).ResultsThe local recurrence rate was higher in group I with 5 years disease‐free survival of 80.0% in group I and 97.0% in group II (p = 0.001). All recurrent cases were noted to have initially presented with soft tissue extension (Enneking stage IB). The mean Musculoskeletal Tumor Society score at the last follow‐up was 21.7 in group I and 27.9 in group II (p = 0.045).ConclusionsIntralesional curettage and cryotherapy for low‐grade chondrosarcoma appear to be a safe and reasonable surgical option for patients with lesions confined to bone (Enneking stage IA).Level of evidenceLevel III, retrospective cohort study. See the Guidelines for Authors for a complete description of levels of evidence.