bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preexisting morbidity profile of women newly diagnosed with breast cancer in sub‐Saharan Africa: African Breast Cancer—Disparities in Outcomes study
Authors: Ayeni Oluwatosin A. , Norris Shane A. , Joffe Maureen , Cubasch Herbert , Galukande Moses , Zietsman Annelle , Parham Groesbeck , Adisa Charles , Anele Angelica , Schüz Joachim , Anderson Benjamin O. , Foerster Milena , dos Santos Silva Isabel , McCormack Valerie A. 
Published: November 2020

AbstractThe presence of preexisting morbidities poses a challenge to cancer patient care. There is little information on the profile and prevalence of multi‐morbidities in breast cancer patients across middle income countries (MIC) to lower income countries (LIC) in sub‐Saharan Africa (SSA). The African Breast Cancer–Disparities in Outcomes (ABC‐DO) breast cancer cohort spans upper MICs South Africa and Namibia, lower MICs Zambia and Nigeria and LIC Uganda. At cancer diagnosis, seven morbidities were assessed: obesity, hypertension, diabetes, asthma/chronic obstructive pulmonary disease, heart disease, tuberculosis and HIV. Logistic regression models were used to assess determinants of morbidities and the influence of morbidities on advanced stage (stage III/IV) breast cancer diagnosis. Among 2189 women, morbidity prevalence was the highest for obesity (35%, country‐specific range 15‐57%), hypertension (32%, 15‐51%) and HIV (16%, 2‐26%) then for diabetes (7%, 4%‐10%), asthma (4%, 2%‐10%), tuberculosis (4%, 0%‐8%) and heart disease (3%, 1%‐7%). Obesity and hypertension were more common in upper MICs and in higher socioeconomic groups. Overall, 27% of women had at least two preexisting morbidities. Older women were more likely to have obesity (odds ratio: 1.09 per 10 years, 95% CI 1.01‐1.18), hypertension (1.98, 1.81‐2.17), diabetes (1.51, 1.32‐1.74) and heart disease (1.69, 1.37‐2.09) and were less likely to be HIV positive (0.64, 0.58‐0.71). Multi‐morbidity was not associated with stage at diagnosis, with the exception of earlier stage in obese and hypertensive women. Breast cancer patients in higher income countries and higher social groups in SSA face the additional burden of preexisting non‐communicable diseases, particularly obesity and hypertension, exacerbated by HIV in Southern/Eastern Africa.
Experiences in the prevention and screening of cervical cancer within Thailand
Authors: Kengsakul Malika , Laowahutanont Piyawat , Wilailak Sarikapan 
Published: November 2020

AbstractCervical cancer is the third most common cancer among Thai women, after breast and colon cancer, with an age‐standardized incidence rate (ASR) of 11.7/100 000 women each year, as of 2015. Over decades, comprehensive national cervical cancer screening programs, research, and the HPV vaccination policy have gradually helped decrease the incidence of cervical cancer in Thailand. In 2017, the Thai Ministry of Public Health signed a memorandum of understanding with the Royal Thai College of Obstetricians and Gynecologists to eliminate invasive cervical cancer from Thailand. This is a tremendous challenge for Thailand as a whole. The present paper reviews and discusses the experiences in the prevention and screening of cervical cancer in Thailand.
Vitamin D Receptor Mediates a Myriad of Biological Actions Dependent on Its 1,25‐Dihydroxyvitamin D Ligand: Distinct Regulatory Themes Revealed by Induction of Klotho and Fibroblast Growth Factor‐23
Authors: Haussler Mark R , Livingston Sarah , Sabir Zhela L , Haussler Carol A , Jurutka Peter W 
Published: November 2020

ABSTRACTThe hormonal vitamin D metabolite, 1,25‐dihydroxyvitamin D [1,25(OH)2D], produced in kidney, acts in numerous end organs via the nuclear vitamin D receptor (VDR) to trigger molecular events that orchestrate bone mineral homeostasis. VDR is a ligand‐controlled transcription factor that obligatorily heterodimerizes with retinoid X receptor (RXR) to target vitamin D responsive elements (VDREs) in the vicinity of vitamin D‐regulated genes. Circulating 1,25(OH)2D concentrations are governed by PTH, an inducer of renal D‐hormone biosynthesis catalyzed by CYP27B1 that functions as the key player in a calcemic endocrine circuit, and by fibroblast growth factor‐23 (FGF23), a repressor of the CYP27B1 renal enzyme, creating a hypophosphatemic endocrine loop. 1,25(OH)2D/VDR–RXR acts in kidney to induce Klotho (a phosphaturic coreceptor for FGF23) to correct hyperphosphatemia, NPT2a/c to correct hypophosphatemia, and TRPV5 and CaBP28k to enhance calcium reabsorption. 1,25(OH)2D‐liganded VDR–RXR functions in osteoblasts/osteocytes by augmenting RANK‐ligand expression to paracrine signal osteoclastic bone resorption, while simultaneously inducing FGF23, SPP1, BGLP, LRP5, ANK1, ENPP1, and TNAP, and conversely repressing RUNX2 and PHEX expression, effecting localized control of mineralization to sculpt the skeleton. Herein, we document the history of 1,25(OH)2D/VDR and summarize recent advances in characterizing their physiology, biochemistry, and mechanism of action by highlighting two examples of 1,25(OH)2D/VDR molecular function. The first is VDR‐mediated primary induction of Klotho mRNA by 1,25(OH)2D in kidney via a mechanism initiated by the docking of liganded VDR–RXR on a VDRE at −35 kb in the mouse Klotho gene. In contrast, the secondary induction of FGF23 by 1,25(OH)2D in bone is proposed to involve rapid nongenomic action of 1,25(OH)2D/VDR to acutely activate PI3K, in turn signaling the induction of MZF1, a transcription factor that, in cooperation with c‐ets1‐P, binds to an enhancer element centered at −263 bp in the promoter‐proximal region of the mouse fgf23 gene. Chronically, 1,25(OH)2D‐induced osteopontin apparently potentiates MZF1. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Piezo1 Inactivation in Chondrocytes Impairs Trabecular Bone Formation
Authors: Hendrickx Gretl , Fischer Verena , Liedert Astrid , von Kroge Simon , Haffner-Luntzer Melanie , Brylka Laura , Pawlus Eva , Schweizer Michaela , Yorgan Timur , Baranowsky Anke , Rolvien Tim , Neven Mona , Schumacher Udo , Beech David J , Amling Michael , Ignatius Anita , Schinke Thorsten 
Published: November 2020

ABSTRACT
The skeleton is a dynamic tissue continuously adapting to mechanical stimuli. Although matrix-embedded osteocytes are considered as the key mechanoresponsive bone cells, all other skeletal cell types are principally exposed to macroenvironmental and microenvironmental mechanical influences that could potentially affect their activities. It was recently reported that Piezo1, one of the two mechanically activated ion channels of the Piezo family, functions as a mechanosensor in osteoblasts and osteocytes. Here we show that Piezo1 additionally plays a critical role in the process of endochondral bone formation. More specifically, by targeted deletion of Piezo1 or Piezo2 in either osteoblast (Runx2Cre) or osteoclast lineage cells (Lyz2Cre), we observed severe osteoporosis with numerous spontaneous fractures specifically in Piezo1Runx2Cre mice. This phenotype developed at an early postnatal stage and primarily affected the formation of the secondary spongiosa. The presumptive Piezo1Runx2Cre osteoblasts in this region displayed an unusual flattened appearance and were positive for type X collagen. Moreover, transcriptome analyses of primary osteoblasts identified an unexpected induction of chondrocyte-related genes in Piezo1Runx2Cre cultures. Because Runx2 is not only expressed in osteoblast progenitor cells, but also in prehypertrophic chondrocytes, these data suggested that Piezo1 functions in growth plate chondrocytes to ensure trabecular bone formation in the process of endochondral ossification. To confirm this hypothesis, we generated mice with Piezo1 deletion in chondrocytes (Col2a1Cre). These mice essentially recapitulated the phenotype of Piezo1Runx2Cre animals, because they displayed early-onset osteoporosis with multiple fractures, as well as impaired formation of the secondary spongiosa with abnormal osteoblast morphology. Our data identify a previously unrecognized key function of Piezo1 in endochondral ossification, which, together with its role in bone remodeling, suggests that Piezo1 represents an attractive target for the treatment of skeletal disorders. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Treatment With Tocilizumab for Patients With COVID‐19 Infections: A Case‐Series Study
Authors: Mo Yoonsun , Adarkwah Obed , Zeibeq John , Pinelis Evgeny , Orsini Jose , Gasperino James 
Published: November 2020

AbstractTocilizumab (TCZ), a humanized monoclonal antibody targeting the interleukin‐6 receptor, holds the potential for treating coronavirus disease 2019 (COVID‐19) patients, particularly those at high risk of cytokine storm syndrome. However, data regarding the clinical impact of treatment with TCZ in patients with COVID‐19 are limited. This study was conducted to evaluate the safety and effectiveness of TCZ as an adjunct therapy for the treatment of severe COVID‐19 infection. This was a retrospective observational chart review of confirmed COVID‐19 patients who received TCZ, along with other COVID‐19 therapies. The outcomes of interest included changes in vital signs such as temperature and laboratory biomarkers, duration of mechanical ventilation, adverse events possibly associated with TCZ, and intensive care unit and hospital lengths of stay. This study included 38 patients with an average age of 63 years (IQR, 48‐70 years). The average dose of TCZ given was 519 ± 61 mg. Median C‐reactive protein significantly decreased following TCZ administration (189.9 vs 54.8 mg/L, P = .003). Nineteen of all febrile patients before the initiation of TCZ (73%) became fever free on the fourth day of TCZ treatment. Following TCZ treatment, 11 patients developed infections because of multidrug‐resistant bacteria, and elevated liver transaminases were observed in 6 patients. The preliminary findings of this study suggested TCZ appeared to ameliorate COVID‐19‐related cytokine storm syndrome. However, large randomized, controlled trials are needed to investigate whether treatment with TCZ is associated with better outcomes in COVID‐19.
Measuring (biological) materials mechanics with atomic force microscopy. 2. Influence of the loading rate and applied force (colloidal particles)
Authors: Weber Andreas , Zbiral Barbara , Iturri Jagoba , Benitez Rafael , Toca‐Herrera José L. 
Published: November 2020

AbstractAtomic force microscopy (AFM) is the most often used tool to study the mechanical properties of eukaryotic cells. Due to their complex assembly, cells show viscoelastic properties. When performing experiments, one has to consider the influence of both loading rate and maximum load on the measured mechanical properties. Here, we employed colloidal particles of various sizes (from 2 to 20 μm diameter) to perform force spectroscopy measurements on endothelial cells at loading rates varying from 0.1 to 50 μm/s, and maximum loads ranging from 1 to 25 nN. We were able to determine the non‐linear dependence of cell viscoelastic properties on the loading rate which followed a weak power law. In addition, we show that previous loading at high forces leads to a stiffening of cells. Based on these results we discuss a road map for determining cell mechanical properties using AFM. Finally, this work provides an experimental framework for cell mechanical measurements using force‐cycle experiments.
Surgery versus external beam radiotherapy for hepatocellular carcinoma involving the inferior vena cava or right atrium: A systematic review and meta‐analysis
Authors: Lee Han Ah , Park Sunmin , Seo Yeon Seok , Yoon Won Sup , Shin In‐Soo , Rim Chai Hong 
Published: November 2020

AbstractWe investigated the efficacy and safety of surgery and external beam radiotherapy (EBRT), in patients with hepatocellular carcinoma (HCC) involving the inferior vena cava (IVC) and/or right atrium (RA) through a comparative meta‐analysis. A systematic search of PubMed, MEDLINE, EMBASE, and the Cochrane library was performed for entries until July 2020. Eighteen studies with 22 cohorts were included, encompassing 755 patients. The pooled median overall survival (OS) and 1‐ and 2‐year OS rates were 14.2 months, 55.6%, and 27.4%, respectively. The pooled median OS in the surgery and EBRT arms were 15.3 and 11.7 months, respectively. The pooled 1‐year OS rate in the surgery arm was significantly higher than that in the EBRT arm (62.4%, 95% CI: 53.8%‐70.3% vs 48.8%, 95% CI: 40.9‐56.8, respectively; P = .023), while the 2‐year OS rates were similar (27.5%, 95% CI: 19.7%‐37.1% vs 26.9%, 95% CI: 20.7‐34.2, respectively; P = .913). In the surgical arm, the perioperative mortality and grade ≥3 complication rates were 0%‐7.6% and 3.9%‐67%, respectively. Grade ≥3 complications and radiation‐induced liver disease were rarely observed in the EBRT arm. Surgery could be an effective local modality for achieving the best survival rate, though it requires efforts to minimize morbidities and careful patient selection. EBRT, as a noninvasive modality, is a valid palliative option, especially for high‐risk patients with a shorter life expectancy.
A new approach for the synthesis of spiro and gem‐dimethyl‐substituted 1,4‐oxazepines from N‐propargylic β‐enaminones
Authors: Karadeniz Eda , Kelgokmen Yilmaz , Zora Metin 
Published: November 2020

AbstractAn efficient and general method for the synthesis of spiro‐1,4‐oxazepines and 3,3‐dimethyl‐1,4‐oxazepines is reported. When treated with ZnI2 and AgSbF6 in refluxing DCE, cyclohexane‐embedded N‐propargylic β‐enaminones underwent 7‐exo‐dig cyclization to afford spiro‐1,4‐oxazepines, specifically 12‐methylene‐11‐oxa‐7‐azaspiro[5.6]dodeca‐7,9‐dienes, in good to high yields. Accordingly, N‐(1,1‐dimethyl)propargylic β‐enaminones produced 3,3‐dimethyl‐1,4‐oxazepines. Cyclization was found to be general for a diverse range of N‐propargylic β‐enaminones with high efficiency and broad functional group tolerance. This operationally easy method might provide quick access to a library of functionalized spiro and gem‐dimethyl‐substituted 1,4‐oxazepine derivatives of pharmacological interest.
Expression of tyrosine pathway enzymes in mice demonstrates that homogentisate 1,2‐dioxygenase deficiency in the liver is responsible for homogentisic acid‐derived ochronotic pigmentation
Authors: Wilson Peter J. M. , Ranganath Lakshminarayan R. , Bou‐Gharios George , Gallagher James A. , Hughes Juliette H. 
Published: November 2020

AbstractAlkaptonuria (AKU) is caused by homogentisate 1,2‐dioxygenase (HGD) deficiency. This study aimed to determine if HGD and other enzymes related to tyrosine metabolism are associated with the location of ochronotic pigment. Liver, kidney, skin, bone, brain, eyes, spleen, intestine, lung, heart, cartilage, and muscle were harvested from 6 AKU BALB/c Hgd−/− (3 females, 3 males) and 4 male C57BL/6 wild type (WT) mice. Hgd, 4‐hydroxyphenylpyruvate dioxygenase (4‐Hppd), tyrosine hydroxylase (Th), and tyrosinase (Tyr) mRNA expression was investigated using qPCR. Adrenal gland and gonads from AKU Hgd tm1a −/− mice were LacZ stained, followed by qPCR analysis of Hgd mRNA. The liver had the highest expression of Hgd, followed by the kidney, with none detected in cartilage or brain. Low‐level Hgd expression was observed within developing male germ cells within the testis and epididymis in Hgd tm1a −/−. 4‐Hppd was most abundant in liver, with smaller amounts in kidney and low‐level expression in other tissues. Th was expressed mainly in brain and Tyr was found primarily in the eyes. The tissue distribution of both Hgd and 4‐Hppd suggest that ochronotic pigment in AKU mice is a consequence of enzymes within the liver, and not from enzymatic activity within ochronotic tissues. Excessive accumulation of HGA as ochronotic pigment in joints and other connective tissues originates from the circulation and therefore the extracellular fluid. The tissue distribution of both Th and Tyr suggests that these enzymes are not involved in the formation of HGA‐derived ochronotic pigment.
Reproducibility of Aorta Segmentation on 4D Flow MRI in Healthy Volunteers
Authors: Juffermans Joe F. , Westenberg Jos J.M. , van den Boogaard Pieter J. , Roest Arno A.W. , van Assen Hans C. , van der Palen Roel L.F. , Lamb Hildo J. 
Published: November 2020

BackgroundHemodynamic aorta parameters can be derived from 4D flow MRI, but this requires lumen segmentation. In both commercially available and research 4D flow MRI software tools, lumen segmentation is mostly (semi‐)automatically performed and subsequently manually improved by an observer. Since the segmentation variability, together with 4D flow MRI data and image processing algorithms, will contribute to the reproducibility of patient‐specific flow properties, the observer's lumen segmentation reproducibility and repeatability needs to be assessed.PurposeTo determine the interexamination, interobserver reproducibility, and intraobserver repeatability of aortic lumen segmentation on 4D flow MRI.Study TypeProspective and retrospective.PopulationA healthy volunteer cohort of 10 subjects who underwent 4D flow MRI twice. Also, a clinical cohort of six subjects who underwent 4D flow MRI once.Field Strength/Sequence3T; time‐resolved three‐directional and 3D velocity‐encoded sequence (4D flow MRI).AssessmentThe thoracic aorta was segmented on the 4D flow MRI in five systolic phases. By positioning six planes perpendicular to a segmentation's centerline, the aorta was divided into five segments. The volume, surface area, centerline length, maximal diameter, and curvature radius were determined for each segment.Statistical TestsTo assess the reproducibility, the coefficient of variation (COV), Pearson correlation coefficient (r), and intraclass correlation coefficient (ICC) were calculated.ResultsThe interexamination and interobserver reproducibility and intraobserver repeatability were comparable for each parameter. For both cohorts there was very good reproducibility and repeatability for volume, surface area, and centerline length (COV = 10–32%, r = 0.54–0.95 and ICC = 0.65–0.99), excellent reproducibility and repeatability for maximal diameter (COV = 3–11%, r = 0.94–0.99, ICC = 0.94–0.99), and good reproducibility and repeatability for curvature radius (COV = 25–62%, r = 0.73–0.95, ICC = 0.84–0.97).Data ConclusionThis study demonstrated no major reproducibility and repeatability limitations for 4D flow MRI aortic lumen segmentation.Level of Evidence3Technical Efficacy Stage2
Predicting Isocitrate Dehydrogenase (IDH)Mutation Status in Gliomas Using MultiparameterMRIRadiomics Features
Authors: Peng Hong , Huo Jiaohua , Li Bo , Cui Yuanyuan , Zhang Hao , Zhang Liang , Ma Lin 
Published: November 2020

BackgroundAccurate and noninvasive detection of isocitrate dehydrogenase (IDH, including IDH1 and IDH2) status is clinically meaningful for molecular stratification of glioma, but remains challenging.PurposeTo establish a model for classifying IDH status in gliomas based on multiparametric MRI.Study TypeRetrospective, radiomics.PopulationIn all, 105 consecutive cases of grade II–IV glioma with 50 IDH1 or IDH2 mutant (IDHm) and 55 IDH wildtype (IDHw) were separated into a training cohort (n =73) and a test cohort (n =32).Field Strength/SequenceContrast‐enhanced T1‐weighted (CE‐T1W), T2‐weighted (T2W), and arterial spin labeling (ASL) images were acquired at 3.0T.AssessmentTwo doctors manually labeled the volume of interest (VOI) on CE‐T1W, then T2W and ASL were coregistered to CE‐T1W. A total of 851 radiomics features were extracted on each VOI of three sequences. From the training cohort, all radiomics features with age and gender were processed by the Mann–WhitneyU‐test, Pearson test, and least absolute shrinkage and selection operator to obtain optimal feature groups to train support vector machine models. The accuracy and area under curve (AUC) of all models for classifying the IDH status were calculated on the test cohort. Two subtasks were performed to verify the efficiency of texture features and the Pearson test in IDH status classification, respectively.Statistical TestsThe permutation test with Bonferroni correction; chi‐square test.ResultsThe accuracy and AUC of the classifier, which combines the features of all three sequences, achieved 0.823 and 0.770 (P < 0.05), respectively. The best model established by texture features only had an AUC of 0.819 and an accuracy of 0.761. The best model established without the Pearson test got an AUC of 0.747 and an accuracy of 0.719.Data ConclusionIDH genotypes of glioma can be identified by radiomics features from multiparameter MRI. The Pearson test improved the performance of the IDH classification models.Level of Evidence4Technical Efficacy Stage1
Numerical solution ofVolterra‐Fredholmintegral equation via hyperbolic basis functions
Authors: Esmaeili Hamid , Rostami Majid , Hooshyarbakhsh Vahideh 
Published: November 2020

AbstractIn this paper, a new method using hyperbolic basis functions is presented to solve second kind linear Volterra‐Fredholm integral equation. In other words, our method approximates the solution of a Volterra‐Fredholm integral equation by the hyperbolic basis functions, which produce block‐pulse functions. Hence, the new method reduces the linear Volterra‐Fredholm integral equation to a system of algebraic equations. Some numerical examples are provided to illustrate the computational efficiency and accuracy of the new method.
Anti‐VEGF antibody delivered locally reduces bony bar formation following physeal injury in rats
Authors: Erickson Christopher B. , Newsom Jake P. , Fletcher Nathan A. , Yu Yangyi , Rodriguez‐Fontan Francisco , Weatherford Shane A. , Hadley‐Miller Nancy , Krebs Melissa D. , Payne Karin A. 
Published: November 2020

AbstractPhyseal injuries can result in the formation of a “bony bar” which can lead to bone growth arrest and deformities in children. Vascular endothelial growth factor (VEGF) has been shown to play a role in bony bar formation, making it a potential target to inhibit bony repair tissue after physeal injury. The goal of this study was to investigate whether the local delivery of anti‐VEGF antibody (α‐VEGF; 7.5 μg) from alginate:chitosan hydrogels to the tibial physeal injury site in rats prevents bony bar formation. We tested the effects of quick or delayed delivery of α‐VEGF using both 90:10 and 50:50 ratio alginate:chitosan hydrogels, respectively. Male and female 6‐week‐old Sprague‐Dawley rats received a tibial physeal injury and the injured site injected with alginate‐chitosan hydrogels: (1) 90:10 (Quick Release); (2) 90:10 + α‐VEGF (Quick Release + α‐VEGF); (3) 50:50 (Slow Release); (4) 50:50 +  α‐VEGF (Slow Release +  α‐VEGF); or (5) Untreated. At 2, 4, and 24 weeks postinjury, animals were euthanized and tibiae assessed for bony bar and vessel formation, repair tissue type, and limb lengthening. Our results indicate that Quick Release + α‐VEGF reduced bony bar and vessel formation, while also increasing cartilage repair tissue. Further, the quick release of α‐VEGF neither affected limb lengthening nor caused deleterious side‐effects in the adjacent, uninjured physis. This α‐VEGF treatment, which inhibits bony bar formation without interfering with normal bone elongation, could have positive implications for children suffering from physeal injuries.