bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ovotransferrin exerts bidirectional immunomodulatory activities via TLR4‐mediated signal transduction pathways in RAW264.7 cells
Authors: Ru Zhiying , Xu Mingsheng , Zhu Gaoxiang , Tu Yonggang , Jiang Yan , Du Huaying 
Published: September 2021

AbstractThe immune regulation function of ovotransferrin (OVT) explored using the RAW264.7 was induced by lipopolysaccharide (LPS) as vitro model in this study. The results showed that RAW264.7 cultured with OVT (200 μg/ml) alone not only enhanced the phagocytic activity and the production and expression of inflammatory factors, but also expression of toll‐like receptor 4 (TLR4) gene was significantly promoted by OVT. OVT (50 μg/ml) significantly inhibited the secretion and expression of inflammatory factors in LPS‐stimulated RAW264.7, but CD14 and TLR4 genes expressions were no obvious effects. Inflammatory cytokines and NO secreted by OVT‐induced macrophages pretreated with inhibitors of TLR4 were down‐regulated. We further verified the effects of OVT on inflammatory signaling pathway‐related proteins through immunofluorescence and western blotting, MyD88, TLR4 and the phosphorylation of IκBα and p65 were significantly promoted by OVT, but there was no significant effects on the phosphorylation of IRF3. OVT promoted the phosphorylation of ERK and p38 in RAW264.7 and inhibited the phosphorylated expression of MAPK in LPS‐mediated inflammation. These results indicated that OVT had the bidirectional immunoregulatory function through TLR4‐mediated NF‐κB/MAPK signaling pathway, that is, anti‐inflammatory effect of low concentration and immune‐enhancing activity of high concentration were showed. That provides a theoretical utilization for the development and utilization of OVT.
The impact of primary care physician density on perinatal health: Evidence from a natural experiment
Authors: Kinge Jonas Minet , Grytten Jostein 
Published: September 2021

AbstractWe examined the impact of primary care physician density on perinatal health outcomes in Norway. From 1992 and onwards, primary care physicians who chose to work in selected remote municipalities were given an annual reduction in their student loan. This reduction, combined with increased supply of physicians, led to an increase in the density of primary care physicians in these selected municipalities. Our register‐based population study showed that this increase in physician density significantly improved perinatal health in terms of fewer fetal deaths and increased birth weight. The richness of the data allowed us to perform several robustness tests.
Cervical dysplasia among migrant women with female genital mutilation/cutting type III: A cross‐sectional study
Authors: Frick Albertina , Azuaga Alicia , Abdulcadir Jasmine 
Published: September 2021

AbstractObjectiveTo assess the rate of cervical dysplasia in a population of migrant women with female genital mutilation/cutting (FGM/C) type III who attended a specialized clinic for FGM/C.MethodsDescriptive retrospective cross‐sectional study reviewing electronic medical records of all infibulated women who attended a specialized clinic for women and girls with FGM/C at Geneva University Hospitals (2010–2016). We examined sociodemographic characteristics, parity, FGM/C subtypes, presence/grade of cervical dysplasia, colposcopy follow up/treatment, infections, and history of sexual violence.ResultsOut of 360 women reviewed, 188 women with FGM/C type III were included. Mean age of the women was 37.7 (±5.14) years. They were mostly from East Africa (n = 116, 61.7%). A total of 113 (60%) had undergone defibulation, the majority (105; 92.9%) without undergoing re‐infibulation. Cervical dysplasia was found in 20 (10.6%): 16 (8.5%) had a low‐grade grade squamous intraepithelial lesion or HPV‐positive atypical squamous cells of undetermined significance, Four (2.1%) had a high‐grade squamous intraepithelial lesions, of which one was a carcinoma in situ. Seven (35%) of the women with dysplasia underwent colposcopies regularly, five (25%) irregularly, and eight (40%) dropped out of colposcopy follow up.ConclusionCervical dysplasia is frequent among women with FGM/C type III and efforts should be made to guarantee follow up for migrant women.
Survey‐based assessment of shifting trends in first solid organ transplant pharmacist jobs
Authors: Horwedel Timothy A. , Crowther Barrett R. , Lourenco Jenkins Laura M. , Doligalski Christina T. , Geyston Jennifer , Suarez Tricia , Fleming James N. 
Published: September 2021

AbstractIntroductionTremendous growth in post‐graduate year 2 (PGY2) and fellowship training opportunities in Solid Organ Transplantation has been seen throughout the 2010s, and efforts to assess the impact and ongoing needs for training are needed.ObjectivesThe American College of Clinical Pharmacy Immunology/Transplantation Practice and Research Network (ACCP IMTR PRN) conducted a survey of its membership in 2018 to assess the initial positions held by its members within the solid organ transplant space in order to evaluate the job market to optimize trainee competitiveness upon graduation.MethodsThe ACCP IMTR PRN Workforce Committee developed a survey through an iterative process assessing pharmacists' first job related to solid organ transplant. Survey content was divided into questions regarding formal training, first job structure, and first job responsibilities. The final survey included 59 questions utilizing branch logic questioning, thus respondents did not answer questions that were not relevant based upon previous responses.ResultsThere were 206 analyzable responses representing pharmacists starting between 1986 and 2017, with the majority starting between 2013 and 2017. Before 2013, 52% of respondents had completed a PGY2 residency specializing in solid organ transplant, compared with 68% of respondents between 2013 and 2017. When comparing responses with first jobs between 2013 and 2017 as compared with the earlier era, more jobs were purely inpatient (32 vs 24%) more were purely dedicated to the transplant population (87 vs 79%), and more had medication order entry as a job responsibility (65 vs 47%).ConclusionsThe results of this survey should be used to help guide the development of post‐graduate specialty training in solid organ transplant to prepare residency and fellowship graduates for first job responsibilities.
Medication nonadherence monitoring and management in adult kidney transplantation: A survey of practices and perceptions at US‐based transplant programs
Authors: Patel Samir J. , Hofmeyer Brooke A. , Moore Cody A. , Descourouez Jillian L. , Nguyen Duc T. , Graviss Edward A. , Taber David J. 
Published: September 2021

AbstractIntroductionMedication nonadherence is a predominant contributor to graft loss, however little is known about currently utilized strategies by transplant centers to monitor or manage this issue.ObjectiveUtilizing standard surveying and analysis techniques, assess health care professionals' (HCPs) perceptions of the scope and scale of medication nonadherence and strategies used to manage this issue at US‐based transplant centers.MethodsA survey to gain insights into pre‐ and post‐transplant medication nonadherence screening, mitigation strategies and perceptions of HCPs regarding nonadherence was developed through an iterative process. This was followed by broad distribution to HCPs at US‐based adult kidney transplant centers. Standard descriptive and comparative statistics were utilized to assess responses and develop inferences and themes from participant responses.ResultsOne hundred and ninety HCPs from 99 centers responded; 56.5% felt medication nonadherence was a major contributor to post‐transplant rejection and graft loss, while 71.1% acknowledged not having a prospective medication nonadherence screening protocol. Of those centers with a protocol, screening declined over time (first post‐transplant month: 92.7%; after 1‐year: <50%). Medication nonadherence management strategies also declined over time (initial transplant stay: 76%; after 1‐year: 6.5%). Few HCPs (24.1%) felt their centers had adequate resources to implement management strategies. Barriers to implement strategies included large patient volume (68.2%) and lack of a validated, easy to use, noninvasive medication nonadherence measure (65.9%).ConclusionWhile HCPs at US‐based adult kidney transplant programs feel that medication nonadherence is a significant issue, the use of systematic processes aimed at prospectively identifying and addressing medication nonadherence is uncommon. Opportunities exist to better address medication nonadherence in kidney transplantation, using feasible noninvasive monitoring and management strategies that align with current HCPs workflow and logistic constraints.
Redox ratio in the left ventricle of the growth restricted fetus is positively correlated with cardiac output
Authors: Dimasi Catherine G. , Lazniewska Joanna , Plush Sally E. , Saini Brahmdeep S. , Holman Stacey L. , Cho Steven K. S. , Wiese Michael D. , Sorvina Alexandra , Macgowan Christopher K. , Seed Mike , Brooks Doug A. , Morrison Janna L. , Darby Jack R. T. 
Published: September 2021

AbstractIntrauterine growth restriction (IUGR) is a result of limited substrate supply to the developing fetus in utero, and can be caused by either placental, genetic or environmental factors. Babies born IUGR can have poor long‐term health outcomes, including being at higher risk of developing cardiovascular disease. Limited substrate supply in the IUGR fetus not only changes the structure of the heart but may also affect metabolism and function of the developing heart. We have utilised two imaging modalities, two‐photon microscopy and phase‐contrast MRI (PC‐MRI), to assess alterations in cardiac metabolism and function using a sheep model of IUGR. Two‐photon imaging revealed that the left ventricle of IUGR fetuses (at 140–141 d GA) had a reduced optical redox ratio, suggesting a reliance on glycolysis for ATP production. Concurrently, the use of PC‐MRI to measure foetal left ventricular cardiac output (LVCO) revealed a positive correlation between LVCO and redox ratio in IUGR, but not control fetuses. These data suggest that altered heart metabolism in IUGR fetuses is indicative of reduced cardiac output, which may contribute to poor cardiac outcomes in adulthood.
Structural characterization of β‐propiolactone inactivated severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) particles
Authors: Bagrov Dmitry V. , Glukhov Grigory S. , Moiseenko Andrey V. , Karlova Maria G. , Litvinov Daniil S. , Zaitsev Petr А. , Kozlovskaya Liubov I. , Shishova Anna A. , Kovpak Anastasia A. , Ivin Yury Y. , Piniaeva Anastasia N. , Oksanich Alexey S. , Volok Viktor P. , Osolodkin Dmitry I. , Ishmukhametov Aydar A. , Egorov Alexey M. , Shaitan Konstantin V. , Kirpichnikov Mikhail P. , Sokolova Olga S. 
Published: September 2021

AbstractThe severe COVID‐19 pandemic drives the research toward the SARS‐CoV‐2 virion structure and the possible therapies against it. Here, we characterized the β‐propiolactone inactivated SARS‐CoV‐2 virions using transmission electron microscopy (TEM) and atomic force microscopy (AFM). We compared the SARS‐CoV‐2 samples purified by two consecutive chromatographic procedures (size exclusion chromatography [SEC], followed by ion‐exchange chromatography [IEC]) with samples purified by ultracentrifugation. The samples prepared using SEC and IEC retained more spikes on the surface than the ones prepared using ultracentrifugation, as confirmed by TEM and AFM. TEM showed that the spike (S) proteins were in the pre‐fusion conformation. Notably, the S proteins could be recognized by specific monoclonal antibodies. Analytical TEM showed that the inactivated virions retained nucleic acid. Altogether, we demonstrated that the inactivated SARS‐CoV‐2 virions retain the structural features of native viruses and provide a prospective vaccine candidate.
Profiling nonhuman primate germline RNA to understand the legacy of early life stress
Authors: Morin Elyse L. , Garza Kristie M. , Aoued Hadj , Sannigrahi Soma , Siebert Erin R. , Howell Brittany R. , Walum Hasse , Sanchez Mar M. , Dias Brian G. 
Published: September 2021

AbstractExposure to stress is a risk factor for perturbed mental health, including impoverished regulation of emotional and physiological responses that accompany anxiety and mood disorders, substance abuse and behavioral disorders. Such disruptions to well‐being could be triggered by discrete environmental events or pervasive early life stress (ELS) resulting for example from adverse caregiving. Recent data mostly collected from rodents exposed to anthropogenic stressors suggest that one way via which the detrimental effects of such stress extend beyond the exposed population to future offspring is via stress‐induced alterations of RNA found in the paternal germline. In contrast, less attention has been paid to how naturally occurring stress in males might influence offspring biology and behavior. In this study, we used a translational nonhuman primate model of ELS caused by naturally occurring adverse caregiving of infant macaques to (1) profile total RNA in the adolescent male germline, and (2) identify how those RNA profiles are affected by exposure to ELS. Our findings that the top 100 transcripts identified correspond to transcripts related to germline biology and reproduction demonstrate the validity and feasibility of profiling RNA in the germline of rhesus macaques. While our small sample sizes precluded definitive assessment of stress‐induced alterations of RNA in the male germline of rhesus macaques that experienced ELS, our study sets the foundation for future investigations of how early adversity might alter the male germline, across species and in experimental protocols that involve anthropogenic vs natural stressors.
Facilitating EMA binding test performance using fluorescent beads combined with next‐generation sequencing
Authors: Glenthøj Andreas , Brieghel Christian , Nardo‐Marino Amina , van Wijk Richard , Birgens Henrik , Petersen Jesper 
Published: September 2021

AbstractThe eosin‐5′‐maleimide (EMA) binding test is widely used as diagnostic test for hereditary spherocytosis (HS), one of the most common haemolytic disorders in Caucasian populations. We recently described the advantages of replacing the use of healthy control blood samples with fluorescent beads in a modified EMA binding assay. In this study we further explore this novel approach. We performed targeted next‐generation sequencing, modified EMA binding test and osmotic gradient ektacytometry on consecutive individuals referred to our laboratory on the suspicion of HS. In total, 33 of 95 carried a (likely) pathogenic variant, and 24 had variants of uncertain significance (VUS). We identified a total 79 different (likely) pathogenic variants and VUS, including 43 novel mutations. Discarding VUS and recessive mutations in STPA1, we used the occurrence of (likely) pathogenic variants to generate a diagnostic threshold for our modified EMA binding test. Twenty‐one of 23 individuals with non‐SPTA1 (likely) pathogenic variants had EMA ≥ 43.6 AU, which was the optimal threshold in receiver operating characteristic (ROC) analysis. Accuracy was excellent at 93.4% and close to that of osmotic gradient ektacytometry (98.7%). In conclusion, we were able to simplify the EMA‐binding test by using rainbow beads as reference and (likely) pathogenic variants to define an accurate cut‐off value.
Routine management, healthcare resource use and patient and carer‐reported outcomes of patients with transfusion‐dependent β‐thalassaemia in the United Kingdom: A mixed methods observational study
Authors: Shah Farrukh , Telfer Paul , Velangi Mark , Pancham Shivan , Wynn Robert , Pollard Sally , Chalmers Elizabeth , Kell Jonathan , Carter Angela M. , Hickey Joe , Paramore Clark , Jobanputra Minesh , Ryan Kate 
Published: September 2021

AbstractObjectivesWe evaluated routine healthcare management, clinical status and patient‐ and carer‐reported outcomes in UK paediatric and adult patients with transfusion‐dependent β‐thalassaemia (TDT).MethodsA multi‐centre, observational mixed‐methodology study evaluated 165 patients (50% male; median age 24.1 [interquartile range (IQR)] 11.8–37.2] years) from nine UK centres.ResultsPatients had a mean of 13.7 (standard deviation [SD] ±3.2) transfusion episodes/year (mean retrospective observation period 4.7 [±0.7] years). The median (IQR) for iron overload parameters at the last assessment during the observation period were: serum ferritin (n = 165) 1961.0 (1090.0–3003.0) μg/L (38% > 2500 μg/L); R2 liver iron (n = 119) 5.4 (2.9–11.6) mg/g (16% ≥15 mg/g); T2* cardiac iron (n = 132) 30.3 (22.0–37.1) ms (10% < 10 ms). All patients received ≥1 iron chelator during the observation period; 21% received combination therapy. Patients had a mean of 7.8 (±8.1) non‐transfusion‐related hospital attendances or admissions/year. Adult patients’ mean EQ‐5D utility score was 0.69 (±0.33; n = 94 [≥16 years]) and mean Transfusion‐dependent quality of life score was 58.6 (±18.4; n = 94 [≥18 years]). For Work Productivity and Activity impairment, mean activity impairment for patients ≥18 years (n = 88) was 48% (±32%) and for carers (n = 29) was 28% (±23%).ConclusionsTDT presents significant burden on patients, carers and healthcare resources.
Differential outcomes for frontal versus posterior demyelination in childhood cerebral adrenoleukodystrophy
Authors: Gupta Ashish O. , Nascene David R. , Shanley Ryan , Kenney‐Jung Daniel L. , Eisengart Julie B. , Lund Troy C. , Orchard Paul J. , Pierpont Elizabeth I. 
Published: September 2021

AbstractIn the most common variant of childhood cerebral adrenoleukodystrophy (cALD), demyelinating brain lesions are distributed predominately in parieto‐occipital white matter. Less frequently, lesions first develop in frontal white matter. This matched cohort study examined whether outcomes after standard treatment with hematopoietic cell transplantation (HCT) differ in patients with early stage frontal lesions as compared to parieto‐occipital lesions. Retrospective chart review identified seven pediatric patients with frontal cALD lesions and MRI severity score < 10 who underwent a single HCT at our center between 1990 and 2019. Concurrent MRI, neurocognitive and psychiatric outcomes at last comprehensive follow‐up (mean 1.2 years; range 0.5‐2.1 years) were compared with a group of seven boys with the parieto‐occipital variant matched on pre‐HCT MRI severity score. Both groups showed similar rates of transplant complications and radiographic disease advancement. Neurocognitive outcomes were broadly similar, with more frequent working memory deficits among individuals with frontal lesions. Psychiatric problems (hyperactivity, aggression, and atypical behavior) were considerably more common and severe among patients with frontal lesions. Aligned with the critical role of the frontal lobes in emotional and behavioral regulation, functional disruption of self‐regulation skills is widely observed among patients with frontal lesions. Comprehensive care for cALD should address needs for psychiatric care and management.
Characterizing the hyper‐ and hypometabolism in temporal lobe epilepsy using multivariate machine learning
Authors: Wu Dongyan , Yang Liyuan , Gong Gaolang , Zheng Yumin , Jin Chaoling , Qi Lei , Li Yanran , Wu Di , Cui Zaixu , He Xiaosong , Ren Liankun 
Published: September 2021

AbstractMesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy, presenting both structural and metabolic abnormalities in the ipsilateral mesial temporal lobe. While it has been demonstrated that the metabolic abnormalities in MTLE actually extend beyond the epileptogenic zone, how such multidimensional information is associated with the diagnosis of MTLE remains to be tested. Here, we explore the whole‐brain metabolic patterns in 23 patients with MTLE and 24 healthy controls using [18F]fluorodeoxyglucose PET imaging. Based on a multivariate machine learning approach, we demonstrate that the brain metabolic patterns can discriminate patients with MTLE from controls with a superior accuracy (>95%). Importantly, voxels showing the most extreme contributing weights to the classification (i.e., the most important regional predictors) distribute across both hemispheres, involving both ipsilateral negative weights over the anterior part of lateral and medial temporal lobe, posterior insula, and lateral orbital frontal gyrus, and contralateral positive weights over the anterior frontal lobe, temporal lobe, and lingual gyrus. Through region‐of‐interest analyses, we verify that in patients with MTLE, the negatively weighted regions are hypometabolic, and the positively weighted regions are hypermetabolic, compared to controls. Interestingly, despite that both hypo‐ and hypermetabolism have mutually contributed to our model, they may reflect different pathological and/or compensative responses. For instance, patients with earlier age at epilepsy onset present greater hypometabolism in the ipsilateral inferior temporal gyrus, while we find no evidence of such association with hypermetabolism. In summary, quantitative models utilizing multidimensional brain metabolic information may provide additional assistance to presurgical workups in TLE.
The Value of Contrast‐Enhanced Ultrasound in Diagnosing Small Renal Cell Carcinoma Subtypes and Angiomyolipoma
Authors: Cao Hongli , Fang Liang , Chen Lin , Zhan Jia , Diao Xuehong , Liu Yingchun , Lu Chen , Zhang Zhengwang , Chen Yue 
Published: September 2021

ObjectivesTo retrospectively explore the value of contrast‐enhanced ultrasound (CEUS) in differentiating small renal cell carcinomas (RCCs) from angiomyolipomas (AMLs), and distinguishing between clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC).MethodsA total of 151 patients with small renal masses (110 ccRCCs, 12 pRCCs, 9 chRCCs, and 20 AMLs) were enrolled between August 2016 and October 2019.ResultsThere were significant differences in terms of enhancement intensity (EI), enhancement homogeneity, perilesional rim‐like enhancement (PRE), wash in, and wash out (WO) between RCC and AML (P = .000, .011, .000, .001, .000, respectively). Although there was no significant difference in EI between pRCC and chRCC (P = .272), EI of ccRCC was higher than that of pRCC (P = .000) and chRCC (P = .010). Multivariate regression analysis showed PRE and fast WO were related to RCC (OR = 18.189, 15.141, respectively). Although there were no significant differences in the sensitivity and area under the curve (AUC) between PRE and fast WO (95.0% vs. 95.0%, P = 1.000 and .880 vs. 0.799, P = .123, respectively), the specificity of PRE in predicting RCC was higher than that of fast WO (80.92% vs. 64.89%, P = .011). The sensitivity, specificity, and AUC of the two characteristics combination for differentiating RCC from AML were 95.0%, 90.8%, and 0.920, respectively, and that of EI for differentiating between ccRCC, pRCC, and chRCC were 81.0%, 78.2%, and 0.796, respectively.ConclusionsCEUS has value in differentiating small RCCs from AMLs and distinguishing ccRCC, a subtype associated with a greater likelihood of malignant behavior from pRCC and chRCC.