bluuebunny/crossref_metadata_2025_split huggingface dataset:
FoxP1 is a transcriptional repressor associated with cancer cachexia that induces skeletal muscle wasting and weakness
Authors: Neyroud Daria , Nosacka Rachel L. , Callaway Chandler S. , Trevino Jose G. , Hu Hui , Judge Sarah M. , Judge Andrew R. 
Published: February 2021

AbstractBackgroundSkeletal muscle wasting is a devastating consequence of cancer that affects up to 80% of cancer patients and associates with reduced survival. Herein, we investigated the biological significance of Forkhead box P1 (FoxP1), a transcriptional repressor that we demonstrate is up‐regulated in skeletal muscle in multiple models of cancer cachexia and in cachectic cancer patients.MethodsInducible, skeletal muscle‐specific FoxP1 over‐expressing (FoxP1iSkmTg/Tg) mice were generated through crossing conditional Foxp1a transgenic mice with HSA‐MCM mice that express tamoxifen‐inducible Cre recombinase under control of the skeletal muscle actin promoter. To determine the requirement of FoxP1 for cancer‐induced skeletal muscle wasting, FoxP1‐shRNA was packaged and targeted to muscles using AAV9 delivery prior to inoculation of mice with Colon‐26 Adenocarcinoma (C26) cells.ResultsUp‐regulation of FoxP1 in adult skeletal muscle was sufficient to induce features of cachexia, including 15% reduction in body mass (P < 0.05), and a 16–27% reduction in skeletal muscle mass (P < 0.05) that was characterized by a 20% reduction in muscle fibre cross‐sectional area of type IIX/B muscle fibres (P = 0.020). Skeletal muscles from FoxP1iSkmTg/Tg mice also showed significant damage and myopathy characterized by the presence of centrally nucleated myofibres, extracellular matrix expansion, and were 19–26% weaker than controls (P < 0.05). Transcriptomic analysis revealed FoxP1 as a potent transcriptional repressor of skeletal muscle gene expression, with enrichment of pathways related to skeletal muscle structure and function, growth signalling, and cell quality control. Because FoxP1 functions, at least in part, as a transcriptional repressor through its interaction with histone deacetylase proteins, we treated FoxP1iSkmTg/Tg mice with Trichostatin A, and found that this completely prevented the loss of muscle mass (p = 0.007) and fibre atrophy (P < 0.001) in the tibialis anterior. In the context of cancer, FoxP1 knockdown blocked the cancer‐induced repression of myocyte enhancer factor 2 (MEF2)‐target genes critical to muscle differentiation and repair, improved muscle ultrastructure, and attenuated muscle fibre atrophy by 50% (P < 0.05).ConclusionsIn summary, we identify FoxP1 as a novel repressor of skeletal muscle gene expression that is increased in cancer cachexia, whose up‐regulation is sufficient to induce skeletal muscle wasting and weakness, and required for the normal wasting response to cancer.
The role of recipient myosteatosis in graft and patient survival after deceased donor liver transplantation
Authors: Czigany Zoltan , Kramp Wiebke , Lurje Isabella , Miller Hannah , Bednarsch Jan , Lang Sven Arke , Ulmer Tom Florian , Bruners Philipp , Strnad Pavel , Trautwein Christian , von Websky Martin Wolfgang , Tacke Frank , Neumann Ulf Peter , Lurje Georg 
Published: February 2021

AbstractBackgroundMyosteatosis is associated with perioperative outcomes in orthotopic liver transplantation (OLT). Here, we investigated the effects of body composition and myosteatosis on long‐term graft and patient survival following OLT.MethodsClinical data from 225 consecutive OLT recipients from a prospective database were retrospectively analysed (May 2010 to December 2017). Computed tomography‐based lumbar skeletal muscle index (SMI) (muscle mass) and mean skeletal muscle radiation attenuation (SM‐RA) (myosteatosis) were calculated using a segmentation tool (3D Slicer). Patients with low skeletal muscle mass (low SMI) and myosteatosis (low SM‐RA) were identified using predefined and validated cut‐off values.ResultsThe mean donor and recipient age was 55 ± 16 and 54 ± 12 years, respectively. Some 67% of the recipients were male. The probability of graft and patient survival was significantly lower in patients with myosteatosis compared with patients with higher SM‐RA values (P = 0.011 and P = 0.001, respectively). Low skeletal muscle mass alone was not associated with graft and patient survival (P = 0.273 and P = 0.278, respectively). Dividing the cohort into quartiles, based on the values of SMI and SM‐RA, resulted in significant differences in patient but not in graft survival (P = 0.011). Even though multivariable analysis identified low SM‐RA as an important prognostic marker (hazard ratio: 2.260, 95% confidence interval: 1.177–4.340, P = 0.014), myosteatosis lost its significance when early mortality (90 days) was excluded from the final multivariable model. Patients with myosteatosis showed significantly higher all‐cause mortality and in particular higher rates of deaths due to respiratory and septic complication (P = 0.002, P = 0.022, and P = 0.049, respectively).ConclusionsPreoperative myosteatosis may be an important prognostic marker in patients undergoing deceased donor liver transplantation. The prognostic value of myosteatosis seems to be particularly important in the early post‐operative phase. Validation in prospective clinical trials is warranted.
Contribution of protein A step towards cost of goods for continuous production of monoclonal antibody therapeutics
Authors: Bansode Vikrant , Gupta Paridhi , Kateja Nikhil , Rathore Anurag S 
Published: February 2021

AbstractBACKGROUNDMonoclonal antibodies (mAbs) presently dominate the biotherapeutic market. However, biotherapeutics in general, and mAbs in particular, are expensive therapies and outside the realm of affordability for most of the world. In an attempt to lower their cost of manufacturing, a novel in‐house non‐protein A continuous platform has recently been reported for mAb purification. In this paper, we perform an in‐depth evaluation of the process economics to assess the impact of removing the protein A step on the cost of goods (COGs).RESULTSThe non‐protein A platform was found to result in significant savings in COGs at about 23% when comparing both platforms in batch mode. Conversion of the non‐protein A platform from batch to continuous mode led to a further increase in these savings with about 39% gains in COGs over the conventional protein A platform.CONCLUSIONSThe non‐protein A purification platform offers a viable alternative to the standard protein A platform and can be considered when setting up a new facility. The continuous non‐protein A platform can especially be considered given the flexibility of the setup and the utility at both small and large scales. © 2021 Society of Chemical Industry
‘Do language and culturereallymatter?’: A trans‐disciplinary investigation of cultural diversity in genetic counseling in Hong Kong
Authors: Zayts‐Spence Olga , Fung Jasmine L. F. , Chung Brian H. Y. 
Published: February 2021

AbstractIn this paper, we present evidence that in counseling culturally diverse patients, differences in spoken language and cultural beliefs of the patients and genetic counseling professionals do not necessarily impede successful counseling. We also highlight sociocultural factors, including socioeconomic background and genetic literacy, that may impact communication in multicultural/ multilingual contexts or when languages other than English are used. While genetic counseling is not short of insights and practical guidelines on sociocultural and language issues, and increasingly, research that employs interviews and surveys, empirical research that draws onauthenticinteractional data (in the form of video‐ and audio‐recorded interactions and their transcripts) is limited. Our goal here is to assess how needs are communicated among a diverse population using an innovative empirical approach that builds on the analysis of transcribed interactions as the primary data and optimizes trans‐disciplinary expertise in linguistics, genetics and genetic counseling. We present data from 42 genetic counseling encounters addressing Sudden Arrhythmic Death Syndrome (SADS) in Hong Kong. We demonstrate the value of thesituatedanalysis of genetic counseling, which focuses on those junctures in the interaction where participants orient to their different linguistic and/or cultural backgrounds asrelevantto the ongoing interaction. We further show that participants draw on various interactional resources to negotiate and resolve possible differences or misunderstandings. We highlight the advantages of incorporating authentic (i.e., non‐simulated) data into the training of genetic counselors to increasecultural awarenessand to provide communication tools (i.e., interactional strategies) they can draw on in their counseling practice.
Uptake of moss‐derived human recombinant GAA in Gaa−/− mice
Authors: Hintze Stefan , Dabrowska‐Schlepp Paulina , Berg Birgit , Graupner Alexandra , Busch Andreas , Schaaf Andreas , Schoser Benedikt , Meinke Peter 
Published: February 2021

AbstractPompe disease, an autosomal recessive lysosomal storage disorder, is caused by deficiency of lysosomal acid alpha‐glucosidase (GAA). On cellular level, there is lysosomal‐bound and free accumulation of glycogen and subsequent damage of organelles and organs. The most severe affected tissues are skeletal muscles and heart. The only available treatment to date is an enzyme replacement therapy (ERT) with alglucosidase alfa, a recombinant human GAA (rhGAA) modified with mannose‐6‐phosphate (M6P), which is internalized via M6P‐mediated endocytosis. There is an unmet need to improve this type of therapy, especially in regard to skeletal muscle. Using different tissue culture models, we recently provided evidence that a moss‐derived nonphosphorylated rhGAA (moss‐GAA), carrying a glycosylation with terminal N‐acetylglucosamine residues (GnGn), might have the potential to improve targeting of skeletal muscle. Now, we present a pilot treatment of Gaa−/− mice with moss‐GAA. We investigated general effects as well as the uptake into different organs following short‐term treatment. Our results do confirm that moss‐GAA reaches the target disease organs and thus might have the potential to be an alternative or complementary ERT to the existing one.
Dynamics of ecosystem carbon stocks in a chronosequence of nitrogen‐fixing Nepalese alder (Alnus nepalensis D. Don.) forest stands in the central Himalayas
Authors: Joshi Rajendra Kr. , Garkoti Satish Chandra 
Published: February 2021

AbstractNitrogen‐fixing Nepalese alder (Alnus nepalensis D. Don.) is a rapidly‐growing pioneer tree species that often forms pure stands in areas affected by landslides, but also occurs mixed with other late‐successional species in the central Himalayas. In this study, we assessed the distribution of carbon in vegetation and soil in a chronosequence of A. nepalensis (3–270 years old) forest stands and evaluated its correlation with the stand and alder total basal area (TBA). The study was conducted in six different naturally occurring forest stands in a chronosequence, viz., alder‐early regenerating (AER), alder‐late regenerating (ALR), alder young‐mixed (AYM), alder mature‐oak (Quercus leucotrichophora) mixed (AMOM), alder mature‐rhododendron (Rhododendron arboreum) mixed (AMR), and alder old‐oak (Q. leucotrichophora) mixed (AOOM) forests. The chronosequence consisted of three young unreserved, AER, ALR, and AYM (age 3–25) and three older reserved, AMOM, AMR, and AOOM (age 80–270) stands. We used structural equation modelling (SEM) to quantify the contribution of various carbon pools on ecosystem carbon stock. Forest carbon stock significantly increased (p < 0.05) with forest age and TBA, indicating that succession is the driving factor of the forest ecosystem processes, carbon accumulation, and therefore, change in vegetation biomass carbon and soil carbon in the chronosequence of A. nepalensis forests. Total vegetation biomass carbon (tree, shrubs, herbs, and litter) contained ~12.54–289.85 Mg ha−1 (79.11–57.77% total carbon stock), and soil carbon (depths of 0–10 cm in AER, 0–30 cm in AYM, 0–100 cm in remaining forest stands) contained ~3.31–210.13 Mg ha−1 (20.8–42% total carbon stock) and positively increased with stand and A. nepalensis TBA. The tree layer biomass carbon stock was considerably higher than the understory (shrubs, herbs, and forest floor). The soil carbon stock was reported to be influenced by the successional stages. Therefore, these findings reflect that the A. nepalensis forest development in the central Himalayas lead to storage of large amount of carbon stock in both plant biomass and soil.
Ageing of PBF‐Grade Poly(Phenylene Sulfide) Powder and its Effect on Critical Printability Properties
Authors: Chatham Camden A. , Das Arit , Long Timothy E. , Bortner Michael J. , Williams Christopher B. 
Published: February 2021

AbstractPoly(phenylene sulfide) (PPS) is a high‐performance polymer suiting the needs of powder bed fusion (PBF) early‐adopter industries. Although there are many benefits to PBF's powder bed‐based, one drawback is thermal ageing of the powder not incorporated into printed parts. Ideally, unfused powder can be reused in future builds; however, it is unlikely that critical printability properties of the thermally aged powder will remain unchanged. Changes in properties lead to either limited reuse through a practice of mixing used and new powder, or elimination of all powder after each build. In this paper, the authors report effects of thermal ageing in simulated printing conditions on properties of PPS critical to PBF processing. PBF‐grade PPS powder is exposed to process‐mimicking conditions. Properties relevant to the three PBF manufacturing process sub‐functions are assessed for the aged powders. Single‐layer prints are made using aged powder to observe polymer‐PBF interactions ad machina. Significant and systematic deviations from the as‐received state of the powder are observed for thermal and coalescence related properties with increasing exposure time and temperature. These changes are interpreted both in terms of physical and chemical changes in PPS and in terms of how these changes may impact the PBF printing process.
Properties of hyperbolic sinusoidal Gaussian beam propagating through strong atmospheric turbulence
Authors: Bayraktar Mert 
Published: February 2021

AbstractThis paper presents evolution of hyperbolic sinusoidal Gaussian (HSG) beam and its point‐like scintillation while propagating through turbulent atmosphere. We benefit from random phase screen approach to evaluate received field and scintillation. We see that astigmatic beams, which source parameters are not equal, are resistive against atmosphere considering intensity distribution. In case of scintillation, all selected HSG beams have less scintillation index than Gauss beam. In addition, astigmatism decreases scintillation at constant Gaussian source size. We anticipate that optical wireless communication devices can be designed using our outputs.
Development and preclinical evaluation of a patient‐specific high energy x‐ray phase sensitive breast tomosynthesis system
Authors: Ghani Muhammad U. , Wu Xizeng , Fajardo Laurie L. , Jing Zhengxue , Wong Molly D. , Zheng Bin , Omoumi Farid , Li Yuhua , Yan Aimin , Jenkins Peter , Hillis Stephen L. , Linstroth Laura , Liu Hong 
Published: February 2021

BackgroundThis article reports the first x‐ray phase sensitive breast tomosynthesis (PBT) system that is aimed for direct translation to clinical practice for the diagnosis of breast cancer.PurposeTo report the preclinical evaluation and comparison of the newly built PBT system with a conventional digital breast tomosynthesis (DBT) system.Methods and materialsThe PBT system is developed based on a comprehensive inline phase contrast theoretical model. The system consists of a polyenergetic microfocus x‐ray source and a flat panel detector mounted on an arm that is attached to a rotating gantry. It acquires nine projections over a 15° angular span in a stop‐and‐shoot manner. A dedicated phase retrieval algorithm is integrated with a filtered back‐projection method that reconstructs tomographic slices. The American College of Radiology (ACR) accreditation phantom, a contrast detail (CD) phantom and mastectomy tissue samples were imaged at the same glandular dose levels by both the PBT and a standard of care DBT system for image quality characterizations and comparisons.ResultsThe PBT imaging scores with the ACR phantom are in good to excellent range and meet the quality assurance criteria set by the Mammography Quality Standard Act. The CD phantom image comparison and associated statistical analyses from two‐alternative forced‐choice reader studies confirm the improvement offered by the PBT system in terms of contrast resolution, spatial resolution, and conspicuity. The artifact spread function (ASF) analyses revealed a sizable lateral spread of metal artifacts in PBT slices as compared to DBT slices. Signal‐to‐noise ratio values for various inserts of the ACR and CD phantoms further validated the superiority of the PBT system. Mastectomy sample images acquired by the PBT system showed a superior depiction of microcalcifications vs the DBT system.ConclusionThe PBT imaging technology can be clinically employed for improving the accuracy of breast cancer screening and diagnosis.
Improving linac integrated cone beam computed tomography image quality using tube current modulation
Authors: Stankovic Uros , Ploeger Lennert S. , Sonke Jan‐Jakob 
Published: February 2021

PurposeLinac integrated cone beam CT (CBCT) scanners have become widespread tool for image guidance in radiotherapy. The current implementation uses constant imaging fluence across all the projection angles, which leads to anisotropic noise properties and suboptimal image quality for noncircular symmetric objects. Tube current modulation (TCM) is widely used in conventional CT. The purpose of this work was to implement TCM on a linac integrated CBCT scanner and evaluate its impact on image quality under varying scatter conditions and scatter correction strategies.MethodsWe have implemented TCM on a nonclinical Elekta Versa HD linear accelerator with enhanced x‐ray generator functionality including pulse width modulation. The pulse width was modulated using two Arduino programmable microcontrollers: one placed on the kV arm to measure the projection angle and the other connected to the kV generator control board to vary x‐ray pulse width as function of gantry angle and precalculated transmission. An in‐house developed phantom with a ratio of the left–right to anterior–posterior path length of 1.85:1 was scanned. Image quality was determined using the anisotropicity of the 2D noise power spectra (NPS) in the transverse plane and the contrast‐to‐noise ratio (CNR). In addition, to determine the impact of scatter on the applicability of the TCM method we have modified the generated scatter using three different collimators in the cranio‐caudal direction as well as with and without an antiscatter grid (ASG).ResultsApplication of the TCM led to 30–78% reduction of the angular anisotropicity of the NPS in the transverse plane. The amount of reduction depended on the scatter conditions, with lower values corresponding to higher scatter conditions. The same was true for the CNR: when scatter contribution was low (presence of an ASG or very aggressive collimation) the CNR was improved by about 30%, while in high scatter conditions the CNR was improved by about 12%.ConclusionsTCM has the potential to improve CBCT image quality, but this depends on the amount of detected x‐ray scatter.
A novel primal‐dual eigenstress‐driven method for shakedown analysis of structures
Authors: Li Kai , Cheng Gengdong , Wang Yu , Liang Yuan 
Published: February 2021

AbstractThe shakedown load of elastoplastic structures under multiple variable loading is an important factor in structural design and integrity analysis. In classical plasticity shakedown analysis is an essential and challenging problem. Most existing methods are based on the solution of super large‐scale mathematical programming, basis reduction or mechanics insight method which have their own limitations in practical engineering problem. In the present study, the proposed method explores the Karush–Kuhn–Tucker (KKT) conditions and the physical reinterpretation of its primal‐dual variables of the Melan's lower bound theorem, and establishes the relation of the primal‐dual variables in finite element formulation. Based on the primal‐dual theory, the primal‐dual eigenstress‐driven method is proposed which is a two‐level nested algorithm: the inner level is the eigenstress‐driven incremental algorithm for constructing the beneficial residual stress field and calculating the safe multiplier and the outer level is the load multiplier descent algorithm for searching the shakedown multiplier. For the purpose of algorithm's universality, the proposed algorithm is fully integrated with the commercial finite element software ANSYS APDL without special optimization solvers, which is well suited for large‐scale practical engineering structures. Several numerical examples are provided to demonstrate the accuracy and efficiency of the proposed algorithm.
You′re brave, I′ll be your friend: Children's evaluations of peers with cancer
Authors: Nash Jane Gradwohl , Weinberger Nanci 
Published: February 2021

AbstractThe focus of this study was to explore children's evaluations of healthy peers and peers with cancer. A racially and ethnically diverse group of fourth‐ and fifth‐grade children (n = 109) viewed a story about a child engaged in a physically challenging rock climbing tower activity at camp. The way the child (healthy or with cancer) ascended and descended the climbing tower (independently or with assistance) was manipulated. Assessment from the participants included their evaluations of the climber (regarding peer acceptance and trait favorability) and their knowledge of cancer. Also, participants’ own behavioral difficulties were assessed by their parents. Results showed that when the climber was healthy, peer acceptance and bravery were higher when ascending independently compared to doing so with assistance. In contrast, the climber with cancer was accepted as a friend and deemed brave, regardless of climbing method. Results revealed that participants had high levels of knowledge about cancer and were likely to know that children with cancer can play outside if they saw just that in the story they heard. These findings suggest that presenting children with cancer engaging in authentic and destigmatizing activities can impact how they are perceived by their potential peers and thus could be an important component for school re‐entry programs.