bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pore‐Size Distribution and Frequency‐Dependent Attenuation in Human Cortical Tibia Bone Discriminate Fragility Fractures in Postmenopausal Women With Low Bone Mineral Density
Authors: Armbrecht Gabriele , Nguyen Minh Huong , Massmann Jonas , Raum Kay 
Published: August 2021

ABSTRACTOsteoporosis is a disorder of bone remodeling leading to reduced bone mass, structural deterioration, and increased bone fragility. The established diagnosis is based on the measurement of areal bone mineral density by dual‐energy X‐ray absorptiometry (DXA), which poorly captures individual bone loss and structural decay. Enlarged cortical pores in the tibia have been proposed to indicate structural deterioration and reduced bone strength in the hip. Here, we report for the first time the in vivo assessment of the cortical pore‐size distribution together with frequency‐dependent attenuation at the anteromedial tibia midshaft by means of a novel ultrasonic cortical backscatter (CortBS) technology. We hypothesized that the CortBS parameters are associated with the occurrence of fragility fractures in postmenopausal women (n = 55). The discrimination performance was compared with those of DXA and high‐resolution peripheral computed tomography (HR‐pQCT). The results suggest a superior discrimination performance of CortBS (area under the receiver operating characteristic curve [AUC]: 0.69 ≤ AUC ≤ 0.75) compared with DXA (0.54 ≤ AUC ≤ 0.55) and a similar performance compared with HR‐pQCT (0.66 ≤ AUC ≤ 0.73). CortBS is the first quantitative bone imaging modality that can quantify microstructural tissue deteriorations in cortical bone, which occur during normal aging and the development of osteoporosis. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
A novel strategy for efficient expression of an antibody fragment in Escherichia coli: ranibizumab as a case study
Authors: Priyanka Priyanka , Rathore Anurag S 
Published: August 2021

AbstractBACKGROUNDComplex biotherapeutics such as non‐glycosylated antibody fragments can be easily manufactured in Escherichia coli due to advancements in recombinant DNA technology. Ranibizumab is one such example of a complex, non‐glycosylated protein used to treat age‐related macular degeneration and macular oedema. Ranibizumab, a humanized monoclonal antibody fragment, is often expressed as inclusion bodies using the E. coli expression system. In this study, we propose a novel strategy for achieving efficient expression of antibody fragments in E. coli BL21 (DE3). Here, the whole antibody fragment (heavy chain + light chain of ranibizumab) has been engineered and cloned in a pET series vector under single promoter belonging to a prokaryotic host along with an extra ribosome binding site to allow equal expression of the light and heavy chains.RESULTSWe demonstrate heterologous expression of ranibizumab with a protein concentration of 0.4 ± 0.019 mg mL–1, confirmed using reversed‐phase high‐performance liquid chromatography with the double copy clone. The reduced and refolded antibody fragment have been analytically characterized using liquid chromatography–mass spectrometry, where masses of the in‐house clone were in correspondence with marketed product. Native polyacrylamide gel electrophoresis and surface plasmon resonance (SPR) analyses were performed to confirm the formation of purified and active recombinant product. Binding kinetics to the target analyte vascular endothelial growth factor of refolded in‐house product was found to be similar to the marketed product as per SPR (12.7 nmol L−1 vs. 10.4 nmol L−1).CONCLUSIONCloning and process optimization have been performed to enhance expression yield. The proposed strategy offers an efficient approach for enhanced production of antibody fragments in microbial hosts. © 2021 Society of Chemical Industry (SCI).
Photoelastic characterization of shear‐bands in mechanically stretched polymeric fibers
Authors: Sokkar Taha Z. N. , El‐Bakary Mohammed A. , Azam Amira A. S. , Hamza Ahmed A. 
Published: August 2021

AbstractIn this work, the shear bands formed during the stretching of isotactic polypropylene fibers are studied. The digital photoelasticity technique is applied to provide full‐field visualization of the stress of the shear bands regions. The mechanical testing device is modified to be suitable for mechanical measurements. The effect of different parameters, that is, the stretching rates and the ambient temperature on the formation of shear bands is investigated. Finally, the influence of heating pre‐existed shear bands is studied. Photoelastic patterns of the shear bands at these conditions are included for illustration.
Following NCCN guidelines within one hospital system in the United States: Comparison between cancer centers and genetic counselor utilization
Authors: Powell Karen , Rakestraw Jonathan , Gupta Sat , Shou Wenhao , Lee Kyung , Leitner Ofri 
Published: August 2021

AbstractGenetic testing is an instrumental tool used to determine whether an individual has a predisposition to certain cancers. Knowing of a hereditary cancer predisposition may allow a patient and their family to consider high‐risk screening or risk‐reducing options. Genetic counselors work with physicians to identify patients at increased risk for genetic testing using available guidelines such as those provided by the National Comprehensive Cancer Network (NCCN). Information within one hospital system's cancer registry was used to identify individuals who qualify for genetic testing. This includes patients with a history of cancer of the breast (diagnosis ≤45, triple negative (TN) ≤60, and male), ovaries, colon (diagnosis ≤50), or uterus (diagnosis ≤50). Within this hospital system's registry, there are six cancer centers. Data were collected from cancer centers that utilized genetic counselors (GCs), and cancer centers that did not (non‐GC) to determine whether there was a difference in genetic testing rates between GC and non‐GC cancer centers. An analysis of 695 patients demonstrated a significantly higher proportion of eligible patients undergoing genetic testing at the GC cancer centers than at the non‐GC cancer centers (91.6% versus 68.7%, p < .001). Further analysis of specific cancers showed a significantly higher uptake of genetic testing for eligible patients with colon cancer (90.8% versus 50%, p < .001), breast cancer ≤45 (99.5% versus 86%, p < .001), and ovarian cancer (91.3% versus 62.8%, p < .001) at the GC cancer centers than at the non‐GC cancer centers. There was no significant difference in the proportion of testing of TN breast cancer ≤60 or uterine cancer ≤50 between cancer centers. These data suggest that having a GC working within a cancer center increases the ability to identify and offer testing to patients who meet NCCN genetic testing criteria based on their cancer type.
Delayed Diagnosis of Idiopathic Subglottic Stenosis
Authors: Berges Alexandra J. , Lina Ioan A. , Chen Lena , Ospino Rafael , Davis Ruth , Hillel Alexander T. 
Published: August 2021

ObjectiveIdiopathic subglottic stenosis (iSGS) is a rare disease, causing life‐threatening dyspnea secondary to scarring. Perhaps because it is rarely encountered, there is often a delay in diagnosing iSGS. The objective of this study is to characterize diagnostic delay of iSGS, factors that prolong delay, and its impact on iSGS patients.Study DesignRetrospective chart review.MethodsA retrospective chart review of 124 iSGS patients was performed. Times of symptom onset, presentation to otolaryngologist, diagnosis, imaging, pulmonary function testing (PFTs), surgeries, emergency department (ED) visits, and hospitalizations were recorded and univariate analyses were used to identify risk factors for delay.ResultsThe median total time to diagnosis from symptom onset was 24.5 months, with time to first presentation of 6.3 months and healthcare delay of 17.8 months. 54.8% of patients were diagnosed with asthma. Earlier presentation to otolaryngologist was associated with shorter healthcare delay and total time to diagnosis (rho = 0.75, rho = 0.99, P < .0001). Earlier CT imaging was correlated to shorter healthcare delay (rho = 0.84, P < .0001) and total time to diagnosis (rho = 0.74, P < .001), while earlier PFTs were correlated to shorter total time to diagnosis alone (rho = 0.71, P = .01). During evaluation, 10.5% (n = 17/124) of patients had ED visits and 13.7% (n = 13/124) patients were hospitalized. Before diagnosis, 7% (9/124) of patients underwent surgeries (including 3% (n = 4) undergoing tracheostomy) and 8% (n = 10) of patients required unplanned urgent endoscopic surgery that may have been avoided with earlier diagnosis.ConclusioniSGS diagnosis is frequently delayed, resulting in additional surgeries (including tracheostomy), ED visits, and hospitalizations. Further, patients' symptoms are commonly attributed to asthma. Earlier otolaryngologist evaluation, PFTs, and CT imaging may expedite iSGS diagnosis.Level of Evidence4 Laryngoscope, 132:413–418, 2022
Anisotropic subloading surface Cam‐clay plasticity model with rotational hardening: Deformation gradient‐based formulation for finite strain
Authors: Yamakawa Yuki , Hashiguchi Koichi , Sasaki Tomohiro , Higuchi Masaki , Sato Kiyoshi , Kawai Tadashi , Machishima Tomohiro , Iguchi Takuya 
Published: August 2021

AbstractThis study is aimed at developing an anisotropic elastoplastic constitutive model for geomaterials at finite strain and its stress calculation algorithm based on the fully implicit return‐mapping scheme. The Cam‐clay plasticity model is adopted as a specific prototype model of geomaterials. As a pertinent representation of deformation‐induced anisotropy in geomaterials, nonlinear rotational hardening is incorporated into the model in a theoretically reasonable manner by introducing the dual multiplicative decompositions of the deformation gradient tensor. In addition to the usual decomposition into elastic and plastic parts, the plastic part is decomposed further into a part contributing to the rotational hardening and a remainder part. The former part leads to a back stress ratio tensor related to the rotational hardening via a hyperelastic‐type hardening rule. The constitutive theory is thereby formulated on proper intermediate configurations entirely in terms of deformation‐like tensorial variables possessing invariance property, without resort to any objective rates of stress or stress‐like variables. Combining the Cam‐clay plasticity with the concept of subloading surface, a class of unconventional plasticity, enables the model to be capable of reproducing complex hardening/softening accompanied by volumetric contractive/dilative responses. Basic characteristics and predictive capability of the proposed model, as well as the accuracy of the developed numerical scheme, are verified through several numerical examples including monotonic and cyclic loadings.
Urinary FABP1 is a biomarker for impaired proximal tubular protein reabsorption and is synergistically enhanced by concurrent liver injury
Authors: Kawakami Ryo , Matsui Miki , Konno Ayumu , Kaneko Ryosuke , Shrestha Shreya , Shrestha Suman , Sunaga Hiroaki , Hanaoka Hirofumi , Goto Sawako , Hosojima Michihiro , Kabasawa Hideyuki , Obokata Masaru , Koitabashi Norimichi , Matsui Hiroki , Sasaki Tsutomu , Saito Akihiko , Yanagita Motoko , Hirai Hirokazu , Kurabayashi Masahiko , Iso Tatsuya 
Published: August 2021

AbstractUrinary fatty acid binding protein 1 (FABP1, also known as liver‐type FABP) has been implicated as a biomarker of acute kidney injury (AKI) in humans. However, the precise biological mechanisms underlying its elevation remain elusive. Here, we show that urinary FABP1 primarily reflects impaired protein reabsorption in proximal tubule epithelial cells (PTECs). Bilateral nephrectomy resulted in a marked increase in serum FABP1 levels, suggesting that the kidney is an essential organ for removing serum FABP1. Injected recombinant FABP1 was filtered through the glomeruli and robustly reabsorbed via the apical membrane of PTECs. Urinary FABP1 was significantly elevated in mice devoid of megalin, a giant endocytic receptor for protein reabsorption. Elevation of urinary FABP1 was also observed in patients with Dent disease, a rare genetic disease characterized by defective megalin function in PTECs. Urinary FABP1 levels were exponentially increased following acetaminophen overdose, with both nephrotoxicity and hepatotoxicity observed. FABP1‐deficient mice with liver‐specific overexpression of FABP1 showed a massive increase in urinary FABP1 levels upon acetaminophen injection, indicating that urinary FABP1 is liver‐derived. Lastly, we employed transgenic mice expressing diphtheria toxin receptor (DT‐R) either in a hepatocyte‐ or in a PTEC‐specific manner, or both. Upon administration of diphtheria toxin (DT), massive excretion of urinary FABP1 was induced in mice with both kidney and liver injury, while mice with either injury type showed marginal excretion. Collectively, our data demonstrated that intact PTECs have a considerable capacity to reabsorb liver‐derived FABP1 through a megalin‐mediated mechanism. Thus, urinary FABP1, which is synergistically enhanced by concurrent liver injury, is a biomarker for impaired protein reabsorption in AKI. These findings address the use of urinary FABP1 as a biomarker of histologically injured PTECs that secrete FABP1 into primary urine, and suggest the use of this biomarker to simultaneously monitor impaired tubular reabsorption and liver function. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Comparative study of far‐field pyroshock responses of epoxy laminated composite panels
Authors: E. Mohamed Najeeb , M. Murugan 
Published: August 2021

AbstractThe experimental study on far‐field pyroshock responses of carbon/glass/Kevlar‐epoxy composite panels are presented in this article. Bi‐Plate Technology is used to conduct all the experiments on different combination of carbon, E‐glass, and Kevlar composite panel parameters, with epoxy resin as matrix. The structural responses computed from the acceleration–time histories are analyzed. Low range of chamber pressure and projectiles of three different lengths are used to carry out the experiments so that the far‐field response of the test panel is ensured. PCB accelerometers and NI‐DAQ system are used to capture the accelerations of panel at selected locations. Among all the composite panels, the one which is of Kevlar‐epoxy laminate shows the least acceleration because the said material has high vibrational energy absorption rate. The glass‐epoxy laminate being higher mass rate shows the intermediate category and the carbon‐epoxy accelerates itself the most. Hence, these types of fibers may be utilized in appropriate areas according to their degree of acceleration to minimize the effect of the far‐field pyroshock response.
Exploring the Role of Manufacturing Parameters on Microstructure and Mechanical Properties in Fused Deposition Modeling (FDM) Using PETG
Authors: Özen Arda , Abali Bilen Emek , Völlmecke Christina , Gerstel Jonathan , Auhl Dietmar 
Published: August 2021

AbstractAdditive manufacturing develops rapidly, especially, fused deposition modeling (FDM) is one of the economical methods with moderate tolerances and high design flexibility. Ample studies are being undertaken for modeling the mechanical characteristics of FDM by using the Finite Element Method (FEM). Even in use of amorphous materials, FDM creates anisotropic structures effected by the chosen manufacturing parameters. In order to investigate these process-related characteristics and tailored properties of FDM structures, we prepare FDM-printed poly(ethylene terephthalate) glycol (PETG) samples with different process parameters. Mechanical and optical characterizations are carried out. We develop 2D-digital-image-correlation code with machine learning algorithm, namely K-means cluster, to analyze microstructures (contact surfaces, the changes in fiber shapes) and calculate porosity. By incorporating these characteristics, we draw CAD images. A digital twin of mechanical laboratory tests are realized by the FEM. We use computational homogenization approach for obtaining the effective properties of the FDM-related anisotropic structure. These simulations are validated by experimental characterizations. In this regard, a systematic methodology is presented for acquiring the anisotropy from the process related inner substructure (microscale) to the material response at the homogenized length scale (macroscale). We found out that the layer thickness and overlap ratio parameters significantly alter the microstructures and thereby, stiffness of the macroscale properties.
Graphical Abstract
Can mechanical circulatory support be an effective treatment for HFpEF patients?
Authors: Gude Einar , Fiane Arnt E. 
Published: August 2021

AbstractHeart failure with preserved ejection fraction (HFpEF) is increasing in prevalence and represents approximately 50% of all heart failure (HF) patients. Patients with this complex clinical scenario, characterized by high filling pressures, and reduced cardiac output (CO) associated with progressive multi-organ involvement, have so far not experienced any significant improvement in quality of life or survival with traditional HF treatment. Left ventricular assist devices (LVAD) have offered a new treatment alternative in terminal heart failure patients with reduced ejection fraction (HFrEF), providing a unique combination of significant pressure and volume unloading together with an increase in CO. The small left ventricular cavity in HFpEF patients challenges left-sided pressure unloading, and new anatomical entry points need to be explored for mechanical pressure and volume unloading. Optimized and pressure/volume-adjusted mechanical circulatory support (MCS) devices for HFrEF patients may conceivably be customized for HFpEF anatomy and hemodynamics. We have developed a long-term MCS device for HFpEF patients with atrial unloading in a pulsed algorithm, leading to a significant reduction of filling pressure, maintenance of pulse pressure, and increase in CO demonstrated in animal testing. In this article, we will discuss HFpEF pathology, hemodynamics, and the principles behind our novel MCS device that may improve symptoms and prognosis in HFpEF patients. Data from mock-loop hemolysis studies, acute, and chronic animal studies will be presented.
Price-based regulation of oligopolistic markets under discrete choice models of demand
Authors: Bortolomiol Stefano , Lurkin Virginie , Bierlaire Michel 
Published: August 2021

AbstractWe propose a framework to find optimal price-based policies to regulate markets characterized by oligopolistic competition and in which consumers make a discrete choice among a finite set of alternatives. The framework accommodates general discrete choice models available in the literature in order to capture heterogeneous consumer behavior. In our work, consumers are utility maximizers and are modeled according to random utility theory. Suppliers are modeled as profit maximizers, according to the traditional microeconomic treatment. Market competition is modeled as a non-cooperative game, for which an approximate equilibrium solution is sought. Finally, the regulator can affect the behavior of all other agents by giving subsidies or imposing taxes to consumers. In transport markets, economic instruments might target specific alternatives, to reduce externalities such as congestion or emissions, or specific segments of the population, to achieve social welfare objectives. In public policy, different agents have different individual or social objectives, possibly conflicting, which must be taken into account within a social welfare function. We present a mixed integer optimization model to find optimal policies subject to supplier profit maximization and consumer utility maximization constraints. Then, we propose a model-based heuristic approach based on the fixed-point iteration algorithm that finds an approximate equilibrium solution for the market. Numerical experiments on an intercity travel case study show how the regulator can optimize its decisions under different scenarios.
Medicamenteuze behandeling van de overactieve blaas: het heden en de toekomst
Authors: Witte L. P. W. , Michel Martin C. 
Published: August 2021

SamenvattingMuscarine-receptorantagonisten en de β3-agonist mirabegron vormen de basis van de medicamenteuze behandeling van het overactieveblaassyndroom (OAB). De effectiviteit van muscarine-receptorantagonisten en mirabegron is vergelijkbaar en de combinatie solifenacine en mirabegron is minimaal effectiever dan dezelfde middelen als monotherapie. De bijwerkingen van antimuscarinica zijn onder andere een droge mond en obstipatie en die van mirabegron zijn vergelijkbaar met placebo. Weinig patiënten gebruiken deze middelen langdurig vanwege een gebrek aan effectiviteit ervan en vanwege de bijwerkingen. Er lijken op dit moment geen middelen met een nieuw werkingsmechanisme in ontwikkeling te zijn en de kans is klein daar op korte termijn verandering in komt. Omdat OAB een symptoomcomplex is, met mogelijk verschillende onderliggende pathologieën en symptoomcombinaties, is het onwaarschijnlijk dat nieuwe middelen duidelijk effectiever zullen zijn. De belangrijkste prioriteiten voor de toekomst zijn niet alleen de ontdekking van nieuwe therapeutische targets, maar ook identificatie van subgroepen met dezelfde symptomatologie of onderliggende pathologie. Biomarkers zouden een rol kunnen spelen bij deze zoektocht.
Endocrine-Disrupting Chemical Exposures in Pregnancy: a Sensitive Window for Later-Life Cardiometabolic Health in Women
Authors: Barrett Emily S. , Groth Susan W. , Preston Emma V. , Kinkade Carolyn , James-Todd Tamarra 
Published: August 2021

Abstract
Purpose of Review
Pregnancy can be seen as a “stress test” with complications predicting later-life cardiovascular disease risk. Here, we review the growing epidemiological literature evaluating environmental endocrine-disrupting chemical (EDC) exposure in pregnancy in relation to two important cardiovascular disease risk factors, hypertensive disorders of pregnancy and maternal obesity.

Recent Findings
Overall, evidence of EDC-maternal cardiometabolic associations was mixed. The most consistent associations were observed for phenols and maternal obesity, as well as for perfluoroalkyl substances (PFASs) with hypertensive disorders. Research on polybrominated flame retardants and maternal cardiometabolic outcomes is limited, but suggestive.

Summary
Although numerous studies evaluated pregnancy outcomes, few evaluated the postpartum period or assessed chemical mixtures. Overall, there is a need to better understand whether pregnancy exposure to these chemicals could contribute to adverse cardiometabolic health outcomes in women, particularly given that cardiovascular disease is the leading cause of death in women.