bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver Sinusoidal Endothelial Cells Suppress Bone Morphogenetic Protein 2 Production in Response to TGFβ Pathway Activation
Authors: Colucci Silvia , Altamura Sandro , Marques Oriana , Dropmann Anne , Horvat Natalie K. , Müdder Katja , Hammad Seddik , Dooley Steven , Muckenthaler Martina U. 
Published: May 2021

Background and Aims
TGFβ/bone morphogenetic protein (BMP) signaling in the liver plays a critical role in liver disease. Growth factors, such as BMP2, BMP6, and TGFβ1, are released from LSECs and signal in a paracrine manner to hepatocytes and hepatic stellate cells to control systemic iron homeostasis and fibrotic processes, respectively. The misregulation of the TGFβ/BMP pathway affects expression of the iron‐regulated hormone hepcidin, causing frequent iron overload and deficiency diseases. However, whether LSEC‐secreted factors can act in an autocrine manner to maintain liver homeostasis has not been addressed so far.

Approach and Results
We analyzed publicly available RNA‐sequencing data of mouse LSECs for ligand‐receptor interactions and identified members of the TGFβ family (BMP2, BMP6, and TGFβ1) as ligands with the highest expression levels in LSECs that may signal in an autocrine manner. We next tested the soluble factors identified through in silico analysis in optimized murine LSEC primary cultures and mice. Exposure of murine LSEC primary cultures to these ligands shows that autocrine responses to BMP2 and BMP6 are blocked despite high expression levels of the required receptor complexes partially involving the inhibitor FK‐506–binding protein 12. By contrast, LSECs respond efficiently to TGFβ1 treatment, which causes reduced expression of BMP2 through activation of activin receptor‐like kinase 5.

Conclusions
These findings reveal that TGFβ1 signaling is functionally interlinked with BMP signaling in LSECs, suggesting druggable targets for the treatment of iron overload diseases associated with deficiency of the BMP2‐regulated hormone hepcidin, such as hereditary hemochromatosis, β‐thalassemia, and chronic liver diseases.
Usefulness of virtual touch tissue quantification for predicting the presence of esophageal varices in patients with liver cirrhosis
Authors: Matsui Teppei , Nagai Hidenari , Watanabe Gou , Yoshimine Naoyuki , Amanuma Makoto , Kobayashi Kojiro , Ogino Yuu , Mukozu Takanori , Matsukiyo Yasushi , Daido Yasuko , Wakui Noritaka , Nakano Shigeru , Shinohara Mie , Momiyama Koichi , Kudo Takehide , Maruyama Kenichi , Igarashi Yoshinori 
Published: May 2021

AbstractBackground and AimMeasuring the hepatic venous pressure gradient (HVPG) is an established technique to detect increased portal pressure and predict the presence of esophageal varices (EVs); however, the risk of the test is greater than the information it provides. This study aimed to clarify the usefulness of virtual touch tissue quantification (VTQ), which assesses liver stiffness, in predicting the presence of EVs in patients with liver cirrhosis by comparing it with HVPG.MethodsTwo hundred seventeen patients with liver cirrhosis underwent VTQ, HVPG measurement, and upper endoscopy. Patients were divided into three groups: group V, hepatitis C virus liver cirrhosis (n = 40); group A, alcoholic liver cirrhosis (n = 116); and group N, other liver cirrhosis (n = 61). In each group, we performed linear regression analysis of VTQ and HVPG data. The accuracy of VTQ and HVPG measurement in predicting the presence of EVs and high‐risk EVs (EV category F2 and F3) was assessed by area under the receiver operating characteristic curve (AUROC).ResultsVTQ was significantly correlated with the HVPG in the whole patients and in each group, and both VTQ and HVPG values were significantly higher in patients with EVs and high‐risk EVs than in those without. The AUROC for the presence of EVs for VTQ was 0.76 in the whole sample, 0.76 in group V, 0.79 in group A, and 0.67 in group N; and for HVPG, 0.92, 0.94, 0.93, and 0.88, respectively. For VTQ, the AUROC for the presence of high‐risk EVs was 0.78 in the whole sample, 0.78 in group V, 0.73 in group A, and 0.73 in group N; and for HVPG, it was 0.85, 0.82, 0.85, and 0.82, respectively.ConclusionVTQ was reliable at predicting the presence of EVs and high‐risk EVs. Therefore, we propose that VTQ is a useful, noninvasive tool for predicting the presence of EVs in daily medical care.
Dual‐contrast computed tomography enables detection of equine posttraumatic osteoarthritis in vitro
Authors: Saukko Annina E. A. , Nykänen Olli , Sarin Jaakko K. , Nissi Mikko J. , te Moller Nikae C. R. , Weinans Harrie , Mancini Irina A. D. , Visser Jetze , Brommer Harold , van Weeren P. Réné , Malda Jos , Grinstaff Mark W. , Töyräs Juha 
Published: May 2021

AbstractTo prevent the progression of posttraumatic osteoarthritis, assessment of cartilage composition is critical for effective treatment planning. Posttraumatic changes include proteoglycan (PG) loss and elevated water content. Quantitative dual‐energy computed tomography (QDECT) provides a means to diagnose these changes. Here, we determine the potential of QDECT to evaluate tissue quality surrounding cartilage lesions in an equine model, hypothesizing that QDECT allows detection of posttraumatic degeneration by providing quantitative information on PG and water contents based on the partitions of cationic and nonionic agents in a contrast mixture. Posttraumatic osteoarthritic samples were obtained from a cartilage repair study in which full‐thickness chondral defects were created surgically in both stifles of seven Shetland ponies. Control samples were collected from three nonoperated ponies. The experimental (n = 14) and control samples (n = 6) were immersed in the contrast agent mixture and the distributions of the agents were determined at various diffusion time points. As a reference, equilibrium moduli, dynamic moduli, and PG content were measured. Significant differences (p < 0.05) in partitions between the experimental and control samples were demonstrated with cationic contrast agent at 30 min, 60 min, and 20 h, and with non‐ionic agent at 60 and 120 min. Significant Spearman's rank correlations were obtained at 20 and 24 h (ρ = 0.482–0.693) between the partition of cationic contrast agent, cartilage biomechanical properties, and PG content. QDECT enables evaluation of posttraumatic changes surrounding a lesion and quantification of PG content, thus advancing the diagnostics of the extent and severity of cartilage injuries.
Multi‐scale attention‐based convolutional neural network for classification of breast masses in mammograms
Authors: Niu Jing , Li Hua , Zhang Chen , Li Dengao 
Published: May 2021

PurposeBreast cancer is the cancer with the highest incidence in women, and early detection can effectively improve the survival rate of patients. Mammography is an important method for physicians to screening breast cancer, but the diagnosis of mammograms by physicians depends largely on clinical practice experience. Studies have shown that using computer‐aided diagnosis techniques can help doctors diagnose breast cancer.MethodsIn this paper, the method of convolutional neural network is mainly used to classify benign and malignant breast masses in the mammograms. First, we use multi‐scale residual networks and densely connected networks as backbone networks to extract the features of global image patches and local image patches. Second, we use the attention module named convolutional block attention module (CBAM) to improve the two feature extraction networks to enhance the network's feature expression ability. Finally, we fuse the features of multi‐scale image patches to achieve the classification of benign and malignant breast masses.ResultsIn the digital database for screening mammography (DDSM) database, the accuracy, sensitivity, AUC value and corresponding standard deviation of our method are 0.9626 ± 0.0110, 0.9719 ± 0.0126, and 0.9576 ± 0.0064, respectively. Compared with the commonly used ResNet (AUC = 0.8823 ± 0.0112) and DenseNet (AUC = 0.9141 ± 0.0085), the performance of our method has improved. In addition, we also used the INbreast database to train and validate the proposed method. The accuracy, sensitivity, AUC and corresponding standard deviations are 0.9554 ± 0.0296, 0.9605 ± 0.0228, and 0.9468 ± 0.0085, respectively.ConclusionsCompared with the previous work, our proposed method uses multi‐scale image features, has better classification performance in breast mass patches classification tasks, and can effectively assist physicians in breast cancer diagnosis.
Relative associations of abdominal and thigh compositions with cardiometabolic diseases in African Caribbean men
Authors: Tilves Curtis , Zmuda Joseph M. , Kuipers Allison L. , Nair Sangeeta , Carr John Jeffrey , Terry James G. , Peddada Shyamal , Wheeler Victor , Miljkovic Iva 
Published: May 2021

AbstractBackgroundRegional body compositions are differentially associated with cardiometabolic risk factors. Simultaneous inclusion of both upper and lower body composition predictors in models is not often done, and studies which do include both measures (1) tend to exclude some tissue(s) of potential metabolic relevance, and (2) have used study populations with underrepresentation of individuals with African ancestries. Further, most body composition analyses do not employ compositional data analytic approaches, which may result in spurious associations.ObjectiveThe objective of this analysis was to assess associations of abdominal and thigh adipose (AT) and muscle tissues with hypertension and type 2 diabetes using compositional data analytic methods.Research Design and MethodsThis cross‐sectional analysis included 610 African Caribbean men (median age: 62 years; mean BMI: 27.8 kg/m2). Abdominal (three components: subcutaneous [ASAT] and visceral [VAT] AT, ‘other’ abdominal tissue) and mid‐thigh (four components: subcutaneous and intermuscular AT, muscle, bone) compositions were measured by computed tomography; additive log ratio transformations were applied to each composition. Regression models were used to simultaneously assess associations of abdominal and thigh component ratios with continuous risk factors (blood pressures, fasting glucose and insulin, HOMA‐IR) and disease categories.ResultsA two‐fold increase in ASAT:‘Other’ ratio was associated with higher continuous risk factors and with odds of being in a higher hypertension (OR: 1.77, 95%CI: 1.10–2.84) or diabetes (OR: 1.81, 95%CI: 1.06–3.10) category. A two‐fold increased VAT ratio was only associated with higher log‐insulin and log‐HOMA‐IR (β = 0.10,p < 0.05 for both), while a two‐fold increased thigh muscle:bone ratio was associated with a lower diabetes category (OR: 0.37, 95%CI: 0.14–1.01).ConclusionsThese findings support ASAT as a significant driver of cardiometabolic disease in African Ancestry populations, independent of other abdominal and thigh tissues.
Methylation profile of imprinted genes provides evidence for teratomatous origin of a subset of mucinous ovarian tumours
Authors: Kato Noriko , Kamataki Akihisa , Kurotaki Hidekachi 
Published: May 2021

AbstractMucinous ovarian tumours are sometimes associated with mature teratomas. It is suggested that the mucinous tumours in this setting are derived from teratomas, but there remains the possibility of collision or metastasis from extra‐ovarian sites. Because mature ovarian teratomas are considered to be parthenogenetic tumours that arise from a single oocyte/ovum, they have only a maternal genome and therefore show maternal genome imprinting. If mucinous ovarian tumours originate from teratomas, their genome imprinting is theoretically maternal. One of the most important mechanisms of genome imprinting is DNA methylation. In the present study, we analysed a total of 28 mucinous ovarian tumours (7 with teratomas, 21 without teratomas; 14 malignant, 14 borderline) to clarify the methylation profiles of their imprinted genes using methylation‐specific multiplex ligation‐dependent probe amplification (MS‐MLPA) of 21 imprinting control regions (ICRs) of nine imprinted genes/gene clusters using formalin‐fixed, paraffin‐embedded samples. All cases lacked evidence of an extra‐ovarian primary mucinous tumour. In all seven mucinous tumours with teratomas, the overall methylation profile of mucinous tumours was comparable to that of teratomas, although some ICRs showed aberrant methylation. In contrast, all but one of the mucinous tumours without teratomas showed somatic or irregular methylation patterns. Morphologically, there was little teratomatous tissue in some mucinous tumours carrying teratoma‐type methylation profiles, suggesting that mucinous tumours overwhelmed ancestral teratomas. In conclusion, the methylation profile of imprinted genes provides evidence that a subset of mucinous ovarian tumours originated from mature teratomas. Genome imprinting‐based analysis is a promising strategy to verify the teratomatous origin of human tumours. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Interface adjustment between poly(ethylene terephthalate) and graphene oxide in order to enhance mechanical and thermal properties of nanocomposites
Authors: de Souza Ziani S. B. , Pinto Gabriel M. , Silva Giovanna da C. , Demarquette Nicole R. , Fechine Guilhermino J. M. , Sobrinho Maurício A. M. 
Published: May 2021

AbstractThere is great interest in the use of graphene and derivatives in the production of polymer nanocomposites as it provides improvements in the properties of the materials to which they are associated. Such improvements depend heavily on filler dispersion and the interaction between the nanomaterials and the matrix. This work aimed to study the compatibility of graphene oxide (GO) with a poly(ethylene terephthalate) matrix. For this, graphite was modified using Hummers method, using reaction times of 3 and 6 h. The obtained GO was functionalized with amine, amide, and magnetite groups (FGO). The effects of the oxidation degree, functionalization and concentration of the nanofillers on the dispersion and consequently on the properties of the polymer nanocomposites were evaluated. The nanocomposites were synthesized by the solid–solid deposition method followed by the melt mixing technique. It was observed that lower concentrations of nanofiller associated with the lower degree of oxidation and functionalization improved the interaction of the nanofillers with the matrix, which resulted in better mechanical properties under tensile stresses for strain at break, maximum stress, Young's modulus and toughness. It was also observed that the glass transition and crystallization of nanocomposites increased due to a nucleating effect of the nanofillers.
Aminoglycoside dosing and monitoring for Pseudomonas aeruginosa during acute pulmonary exacerbations in cystic fibrosis
Authors: Ochs Madeleine A. , Dillman Nicholas O. , Caverly Lindsay J. , Chaffee Valerie D. 
Published: May 2021

AbstractAminoglycosides are commonly used for the treatment of Pseudomonas aeruginosa (PsA) in the setting of acute pulmonary exacerbations (PEx) in pediatric patients with cystic fibrosis (CF). There are controversies and practice differences between institutions related to aminoglycoside dosing and monitoring strategies. The purpose of this review article is to summarize the currently available literature and identify gaps in the literature related to pharmacokinetic parameter goals, aminoglycoside dosing strategies, and methods for monitoring serum aminoglycoside concentrations for treatment of PsA in CF PEx, and throughout will discuss anticipated changes with the increasing availability of highly effective CF transmembrane conductance regulator modulators. This review focuses on tobramycin, as it is the most commonly used aminoglycoside in CF PEx, and will briefly discuss special circumstances surrounding use of amikacin and gentamicin.
Can laboratory findings predict pulmonary involvement in children with COVID‐19 infection?
Authors: Böncüoğlu Elif , Coşkun Mehmet , Kıymet Elif , Öztürk Atasoy Tülay , Şahinkaya Şahika , Cem Ela , Düzgöl Mine , Yılmaz Çelebi Miray , Akaslan Kara Aybüke , Arıkan Kamile Ö. , Bayram Nuri , Devrim İlker 
Published: May 2021

AbstractBackgroundStudies investigating clinical and imaging findings of coronavirus disease 2019 (COVID‐19) pneumonia and predictors for lung injury mostly focus on adults. In this study, we aimed to evaluate the role of laboratory findings in predicting lung involvement in children with COVID‐19.MethodsChildren with COVID‐19 confirmed by reverse‐transcription polymerase chain reaction or COVID‐19 IgM and who underwent chest computed tomography (CT) scans were reviewed retrospectively. Admission absolute neutrophil count (ANC), absolute lymphocyte count (ALC), ANC/ALC ratio, platelet count, D‐dimer, fibrinogen, ferritin, procalcitonin, C‐reactive protein (CRP), and lactate dehydrogenase levels were compared in patients with normal and abnormal CT scans.ResultsA total of 101 children were included. Among the patients, 68 (67.3%) had normal CT scans, and 33 (32.7%) had pulmonary involvement. The median CRP, ferritin, and fibrinogen levels were significantly higher in children with abnormal CT findings. The model of binary logistic regression based on the presence of cough, shortness of breath, fibrinogen, ferritin, and CRP levels showed that the possibility of having abnormal CT was 1.021 times more likely for every one unit increase in fibrinogen levels.ConclusionFibrinogen might be useful to predict pulmonary involvement of COVID‐19 in children. Restricting radiological imaging to patients with significant symptoms and high fibrinogen levels might be helpful in children with COVID‐19 infections.
Characterization of the multidrug efflux transporter styMdtM from Salmonella enterica serovar Typhi
Authors: Shaheen Aqsa , Ismat Fouzia , Iqbal Mazhar , Haque Abdul , Ul‐Haq Zaheer , Mirza Osman , De Zorzi Rita , Walz Thomas , Rahman Moazur 
Published: May 2021

AbstractSalmonellae are foodborne pathogens and the major cause of gastroenteritis in humans. Salmonellae express multidrug efflux transporters that play a key role in their drug resistance, which is becoming an increasing problem for therapeutic intervention. Despite their biomedical importance, the mechanisms underlying substrate transport by multidrug efflux transporters remain poorly understood. Here, we describe the first characterization of a multidrug transporter belonging to the major facilitator superfamily from the genus Salmonella. We show that several clinical Salmonella Typhi (S. Typhi) isolates constitutively express the styMdtM (STY4874) gene, which encodes a known multidrug‐resistance (MDR) transporter. Guided by the structure of the Escherichia coli (E. coli) homolog, we studied two residues critical for substrate transport, Asp25 and Arg111. Mutation of Asp25 to glutamate did not affect the transport function of styMdtM, whereas mutation to alanine reduced its transport activity, suggesting that a negative charge at this position is critical for substrate translocation across the membrane. Substrate‐affinity measurements by intrinsic fluorescence spectroscopy showed that the Asp25Ala mutant retained its capacity to bind substrate, albeit at a lower level. Mutation of Arg111 to alanine resulted in a decrease in secondary structure content of the transporter, and mutation to lysine completely destabilized the structure of the transporter. A homology model of styMdtM suggests that Arg111 is important for stabilizing the transmembrane domain by mediating necessary interactions between neighboring helices. Together, our studies provide new structural and mechanistic insights into the Salmonella MDR transporter styMdtM.
Fungal Ice2p is in the same superfamily as SERINCs, restriction factors for HIV and other viruses
Authors: Alli‐Balogun Ganiyu O. , Levine Tim P. 
Published: May 2021

AbstractIce2p is an integral endoplasmic reticulum (ER) membrane protein in budding yeast S. cerevisiae named ICE because it is required for Inheritance of Cortical ER. Ice2p has also been reported to be involved in an ER metabolic branch‐point that regulates the flux of lipid either to be stored in lipid droplets or to be used as membrane components. Alternately, Ice2p has been proposed to act as a tether that physically bridges the ER at contact sites with both lipid droplets and the plasma membrane via a long loop on the protein's cytoplasmic face that contains multiple predicted amphipathic helices. Here we carried out a bioinformatic analysis to increase understanding of Ice2p. First, regarding topology, we found that diverse members of the fungal Ice2 family have 10 transmembrane helices (TMHs), which places the long loop on the exofacial face of Ice2p, where it cannot form inter‐organelle bridges. Second, we identified Ice2p as a full‐length homolog of SERINC (serine incorporator), a family of proteins with 10 TMHs found universally in eukaryotes. Since SERINCs are potent restriction factors for HIV and other viruses, study of Ice2p may reveal functions or mechanisms that shed light on viral restriction by SERINCs.
Does atorvastatin therapy change the anti‐Xa activity in xabans‐treated patients with atrial fibrillation?
Authors: Škorňová Ingrid , Samoš Matej , Bolek Tomáš , Stančiaková Lucia , Vádelová Ľubica , Galajda Peter , Staško Ján , Kubisz Peter , Mokáň Marián 
Published: May 2021

AbstractAtorvastatin and direct oral factor Xa inhibitors (xabans) are frequently co‐administrated in patients with atrial fibrillation (AF). However, no studies investigating the possibility of the pharmacologic interaction between these agents have been conducted. The aim of this prospective observational study was to determine the impact of atorvastatin therapy on anti‐Xa activity in xabans‐treated patients with AF. We enrolled 115 AF patients on long‐term rivaroxaban (52 patients) and long‐term apixaban (63 patients) therapy. Long‐term atorvastatin (40 mg once daily) was administrated to 28 rivaroxaban‐treated patients and to 28 apixaban‐treated patients. Trough and peak samples were tested for anti‐Xa activity with drug‐specific anti‐Xa chromogenic analysis. For rivaroxaban, there were no significant differences in trough activity (45.5 ± 39.5 ng/ml vs. 46.2 ± 30.1 ng/ml; p = .34) and peak anti‐Xa activity (179.2 ± 108.8 ng/ml vs. 208.1 ± 104.1 ng/ml; p = .94) between atorvastatin‐treated patients and those without atorvastatin. Similarly, atorvastatin did not impact the trough activity (127.7 ± 71.1 ng/ml vs. 100.8 ± 61.1 ng/ml; p = .12) or peak anti‐Xa activity (213.8 ± 103.6 ng/ml vs. 179.3 ± 72.9 ng/ml; p = .14) among apixaban‐treated patients with AF. This observational study did not show a significant impact of atorvastatin on trough and peak anti‐Xa activity in xabans‐treated patients with AF.
Back Cover Image, Volume 77, Issue 6
Authors: Morrison William R , Scully Erin D , Campbell James F 
Published: May 2021

The back cover image is based on the Review Towards developing areawide semiochemical‐mediated, behaviorally‐based integrated pest management programs for stored product insects by William R Morrison III et al., https://doi.org/10.1002/ps.6289.
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