bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human pluripotent stem cell-derived kidney organoids for personalized congenital and idiopathic nephrotic syndrome modeling
Authors: Jansen Jitske , van den Berge Bartholomeus T , van den Broek Martijn , Maas Rutger J , Willemsen Brigith , Kuppe Christoph , Reimer Katharina C , Giovanni Gianluca Di , Mooren Fieke , Nlandu Quincy , Mudde Helmer , Wetzels Roy , den Braanker Dirk , Parr Naomi , Nagai James S , Drenic Vedran , Costa Ivan G , Steenbergen Eric , Nijenhuis Tom , Endlich Nicole , van de Kar Nicole CAJ , Schneider Rebekka K , Wetzels Jack FM , van der Vlag Johan , Kramann Rafael , Schreuder Michiel F , Smeets Bart 
Published: October 2021

AbstractNephrotic syndrome (NS) is characterized by severe proteinuria as a consequence of kidney glomerular injury due to podocyte damage. In vitro models mimicking in vivo podocyte characteristics are a prerequisite to resolve NS pathogenesis. Here, we report human induced pluripotent stem cell derived kidney organoids containing a podocyte population that heads towards adult podocytes and were superior compared to 2D counterparts, based on scRNA sequencing, super-resolution imaging and electron microscopy. In this study, these next-generation podocytes in kidney organoids enabled personalized idiopathic nephrotic syndrome modeling as shown by activated slit diaphragm signaling and podocyte injury following protamine sulfate treatment and exposure to NS plasma containing pathogenic permeability factors. Organoids cultured from cells of a patient with heterozygous NPHS2 mutations showed poor NPHS2 expression and aberrant NPHS1 localization, which was reversible after genetic correction. Repaired organoids displayed increased VEGFA pathway activity and transcription factor activity known to be essential for podocyte physiology, as shown by RNA sequencing. This study shows that organoids are the preferred model of choice to study idiopathic and congenital podocytopathies.Summary StatementKidney organoid podocytes allow personalized nephrotic sydrome modeling,
Investigating Biases Associated with Dietary Starch Incorporation and Retention with an Oral Biofilm Model
Authors: Bartholdy Bjørn Peare , Henry Amanda G. 
Published: October 2021

AbstractDental calculus has proven to contain a wealth of information on the dietary habits of past populations. These insights have, to a large extent, been obtained by the extraction and identification of starch granules contained within the mineralised dental plaque from a wide range of regions and time periods. The scope of previous studies have been limited to microfossil extraction and identification to reconstruct dietary preferences from the archaeological record, and few studies have attempted to address the biases of starch retention in dental calculus. Those that have considered this problem have been limited toin vivostudies on modern humans and non-human primates. Here, we present a multispecies oral biofilm model, which allows experimental research on starch incorporation and retention to be conducted onin vitrodental calculus in a controlled laboratory setting. The biofilms were exposed to treatment solutions with known quantities of dietary starches (wheat and potato) during the 25-day growth period. After this, the starch granules were extracted from the mature biofilm (by dissolution in EDTA), and counted. We show that the granule counts extracted from the model dental calculus represented a low proportion (ranging from 0.06% to 0.16%) of the total number of granules exposed to the biofilms throughout the experiment. Additionally, we found that the ratios of granule sizes from the extracted starch granules differed from the original treatment solutions, with large granules (>20μm) consistently being under-represented. We also found a correlation between the absolute granule counts and dry-weight of the biofilm (r= 0.66, 90%CI[0.46,0.79]), as well as between the concentration (count per mg) of granules and dry-weight (r= 0.30, 90%CI[0.06,0.51]).Our results reinforce previousin vivostudies suggesting that dental calculus presents a very small, and partly biased picture of the original dietary intake of starches, with an over-representation of plants producing granules smaller than 20μm in size. The experimental model presented here is well-suited to address the need for further validation of methods and biases associated with dietary research on dental calculus.
Syrbactin-class dual constitutive- and immuno-proteasome inhibitor TIR-199 impedes myeloma-mediated bone degenerationin vivo
Authors: Tandon Vasudha , Vala Ruturajsinh M , Chen Albert , Sah Robert L , Patel Hitendra M , Pirrung Michael C , Banerjee Sourav 
Published: October 2021

AbstractProteasome-addicted neoplastic malignancies present a considerable refractory and relapsed phenotype with patients exhibiting drug-resistance and high mortality rates. To counter this global problem, novel proteasome-based therapies are being developed. In the current study we extensively characterize TIR-199, a syrbactin-class proteasome inhibitor derived from a plant virulence factor of bacteriumPseudomonas syringae pv syringae.We report that TIR-199 is a potent constitutive and immunoproteasome inhibitor, capable of inducing cell death in multiple myeloma, triple-negative breast cancer and non-small cell lung cancer lines, effectively inhibit proteasome in primary myeloma cells of refractory patients, and bypass the PSMB5 A49T+A50V bortezomib-resistant mutant. TIR-199 treatment leads to accumulation of canonical proteasome substrates in cells, it is specific, and does not inhibit 50 other enzymes tested in vitro. The drug exhibits synergistic cytotoxicity in combination with proteasome-activating-kinase DYRK2 inhibitor LDN192960. Furthermore, low dose TIR-199 exhibits in vivo activity in delaying myeloma-mediated bone degeneration in a mouse xenograft model. Together, our data indicates that proteasome inhibitor TIR-199 could indeed be a next generation drug within the repertoire of proteasome-based therapeutics with a potential to target relapsed and refractory proteasome-addicted neoplasia.
Ultra-deep sequencing reveals no evidence of oncogenic mutations or enrichment by ex vivo CRISPR/Cas9 genome editing in human hematopoietic stem and progenitor cells
Authors: Cromer M. Kyle , Barsan Valentin V. , Jaeger Erich , Wang Mengchi , Hampton Jessica P. , Chen Feng , Kennedy Drew , Khrebtukova Irina , Granat Ana , Truong Tiffany , Porteus Matthew H. 
Published: October 2021

AbstractAs CRISPR-based therapies enter the clinic, evaluation of the safety remains a critical and still active area of study. While whole genome sequencing is an unbiased method for identifying somatic mutations introduced by ex vivo culture and genome editing, this methodology is unable to attain sufficient read depth to detect extremely low frequency events that could result in clonal expansion. As a solution, we utilized an exon capture panel to facilitate ultra-deep sequencing of >500 tumor suppressors and oncogenes most frequently altered in human cancer. We used this panel to investigate whether transient delivery of high-fidelity Cas9 protein targeted to three different loci (using guide RNAs (gRNAs) corresponding to sites at AAVS1, HBB, and ZFPM2) at day 4 and day 10 timepoints post-editing resulted in the introduction or enrichment of oncogenic mutations. In three separate primary human HSPC donors, we identified a mean of 1,488 variants per Cas9 treatment (at <0.07% limit of detection). After filtering to remove germline and/or synonymous changes, a mean of 3.3 variants remained per condition, which were further reduced to six total mutations after removing variants in unedited treatments. Of these, four variants resided at the predicted off-target site in the myelodysplasia-associated EZH2 gene that were subject to ZFPM2 gRNA targeting in Donors 2 and 3 at day 4 and day 10 timepoints. While Donor 1 displayed on-target cleavage at ZFPM2, we found no off-target activity at EZH2. Sanger sequencing revealed a homozygous single nucleotide polymorphism (SNP) at position 14bp distal from the Cas9 protospacer adjacent motif in EZH2 that eliminated any detectable off-target activity. We found no evidence of exonic off-target INDELs with either of the AAVS1 or HBB gRNAs. These findings indicate that clinically relevant delivery of high-fidelity Cas9 to primary HSPCs and ex vivo culture up to 10 days does not introduce or enrich for tumorigenic variants and that even a single SNP outside the seed region of the gRNA protospacer is sufficient to eliminate Cas9 off-target activity with this method of delivery into primary, repair competent human HSPCs.
Auditory Brainstem Responses in the C57BL/6J Fragile X Syndrome Knockout Mouse Model
Authors: Chawla Amita , McCullagh Elizabeth A 
Published: October 2021

AbstractSensory hypersensitivity, especially in the auditory system, is a common symptom in Fragile X Syndrome (FXS), the most common monogenic form of intellectual disability. However, linking phenotypes across genetic background strains of mouse models has been a challenge and could underly some of the issues with translatability of drug studies to the human condition. This study is the first to characterize the auditory brainstem response (ABR), a minimally invasive physiological readout of early auditory processing that is also used in humans, in a commonly used mouse background strain model of FXS, C57BL/6J. We measured morphological features of pinna and head and used ABR to measure hearing range, monaural and binaural auditory responses in hemizygous males, homozygous females and heterozygous females compared to wildtype mice. Consistent with previous work we showed no difference in morphological parameters across genotypes or sexes. Male FXS mice had increased threshold for high frequency hearing at 64 kHz compared to wildtype males, while females had no difference in hearing range between genotypes. In contrast, female homozygous FXS mice had decreased amplitude of wave IV of the monaural ABR, while there was no difference in males for amplitudes and no change in latency of ABR waveforms across sexes and genotypes. Lastly, FXS males had increased latency of the binaural interaction component (BIC) at 0 ITD compared to wildtype males. These findings further clarify auditory brainstem processing in FXS by adding more information across genetic background strains allowing for a better understanding of shared phenotypes.
Coccolith Sr/Ca is a Robust Temperature and Growth Rate Indicator that Withstands Dynamic Microbial Interactions
Authors: Eliason Or , Segev Einat 
Published: October 2021

AbstractCoccolithophores are a diverse group of calcifying microalgae that have left a prominent fossil record on Earth. Various coccolithophore relics, both organic and inorganic, serve as proxies for reconstruction of past oceanic conditions.Emiliania huxleyi is the most widely distributed representative of the coccolithophores in modern oceans, and is known to engage in dynamic interactions with bacteria. Algal-bacterial interactions influence various aspects of algal physiology and alter algal alkenone unsaturation (UK’37), a frequently used organic coccolithophore-derived paleotemperature proxy. Whether algal-bacterial interactions influence inorganic coccolithophore-derived paleo-proxies, is yet unknown.A commonly used inorganic proxy for past productivity and sea surface temperature is the Sr/Ca ratio of the coccolith calcite. Interestingly, during interactions between bacteria and a population of calcifying algae, bacteria were shown to physically attach only to non-calcified algal cells, suggesting an influence on algal calcification.In this study we explore the effects of algal-bacterial interactions on calcification and coccolith Sr/Ca ratios. We find that while bacteria attach only to non-calcified algal cells, coccolith cell coverage and overall calcite production in algal populations with and without bacteria, is similar. Furthermore, we find that Sr/Ca values are impacted only by water temperature and algal growth rate, regardless of bacterial influences on algal physiology. Our observations reinforce the robustness of coccolith Sr/Ca ratios as a paleo-proxy independent of microbial interactions, and highlight a fundamental difference between organic and inorganic paleo-proxies.Summary StatementThe current research investigates the effect of microbial interactions on coccolith Sr/Ca ratio and overall calcification in the coccolithophore Emiliania huxleyi. We co-cultured E. huxleyi with the marine bacterium Phaeobacter inhibens and compared coccolith Sr/Ca between different growth stages in a range of temperatures. Our results indicate that coccolith Sr/Ca depends on temperature and algal growth rate, and remains robust despite significant bacterial influences on algal physiology.
Corrosion protection of some Cu-based alloys by polyacrylate-alumina nanocomposite coatings
Authors: Attia Adel , Khorshed Lobna , Morsi Samir , Ashour Elsayed 
Published: October 2021

Purpose
The purpose of this study was to investigate the polyacrylic polymer/Al2O3 as a new nanocomposite coating to protect brass and Al-bronze in 3.5% NaCl and the role of alumina formulation on their protection efficiency

Design/methodology/approach
The corrosion efficiency of the nanocomposite coating (NCC) was evaluated by open circuit potential and electrochemical impedance spectroscopy (EIS).

Findings
The protection efficiency was more in the case of Al-bronze even for the same formulation of alumina NCC indicated the Cu substrate contribution. The Cu oxides in alloys and Al2O3 from the NCC and Al-bronze were responsible for this protection.

Originality/value
All the techniques supported each other, the presence of alumina was responsible for the corrosion protection efficiency.
Evaluation of the corrosion behavior of AZ31 magnesium alloy with different protein concentrations
Authors: Ma Yucong , Talha Mohd , Wang Qi , Li Zhonghui , Lin Yuanhua 
Published: October 2021

Purpose
The purpose of this paper is to study systematically the corrosion behavior of AZ31 magnesium (Mg) alloy with different concentrations of bovine serum albumin (BSA) (0, 0.5, 1.0, 1.5, 2.0 and 5.0 g/L).

Design/methodology/approach
Electrochemical impedance spectroscopy and potential dynamic polarization tests were performed to obtain corrosion parameters. Scanning electrochemical microscopy (SECM) was used to analyze the local electrochemical activity of the surface film. Atomic force microscope (AFM), Scanning electron microscope-Energy dispersive spectrometer and Fourier transform infrared spectroscopy were used to determine the surface morphology and chemical composition of the surface film.

Findings
Experimental results showed the presence of BSA in a certain concentration range (0 to 2.0 g/L) has a greater inhibitory effect on the corrosion of AZ31, however, the presence of high-concentration BSA (5.0 g/L) would sharply reduce the corrosion resistance.

Originality/value
When the concentration of BSA is less than 2.0 g/L, the corrosion resistance of AZ31 enhances with the concentration. The adsorption BSA layer will come into being a physical barrier to inhibit the corrosion process. However, high-concentration BSA (5.0 g/L) will chelate with dissolved metal ions (such as Mg and Ni) to form soluble complexes, which increases the roughness of the surface and accelerates the corrosion process.
Designing two-period decentralized service chain incentives with the consideration of customer acquisition and retention
Authors: Wang Tian , Duan Yunan , Liang Yangyang 
Published: October 2021

PurposeThe authors address a two-dimensional (both customer acquisition and retention) incentive in a decentralized service chain consisting of a risk-neutral brand and agent (or averse). Design/methodology/approachThe authors focus on the relationship between acquisition and retention, that is, retained customers (repeated purchases) are based on and come from the acquired (new) customers in the former period. The authors also design a two-period separate incentive on both dimensions.FindingsThe authors found that a targeted incentive strategy should be applied for achieving more revenue when the incentive intensities are relatively small. Otherwise, the brand needs to adjust the targeted incentive strategy into incentivizing the opposite dimension, particularly on acquisition. Under the optimal contract, the brand needs to be very careful with deciding the fixed part of the incentive salary and the incentive intensities on both dimensions. For example, the fixed salary initially decreases and then increases in the incentive intensities. For the optimal incentive policies, the brand should incentivize acquisition but outsource retention if the agent is risk-neutral. When the agent is becoming risk-averse, the brand should lower its incentive intensity as the risk degree and variances become larger. Interestingly, the brand may benefit from introducing risks.Originality/valueThe study contributes to the literature by considering the following points. First, the authors extend the principal-agent incentive model by considering two-period decisions of customer acquisition and retention. Second, based on the two-period principal-agent problem, the authors design separate incentive intensities on acquisition and retention, respectively. While, most of the literature focused on acquisition incentives. Third, different from other works focusing on either risk-neutral or risk-averse environments, the authors consider both and compare the cases of risk-neutral and risk-averse to analyze the impact of risk on the optimal decisions and the brand's expected profit.
Quality intervention, supplier performance and buyer–supplier relationships: evidence from the garment industry
Authors: Hoque Imranul , Maalouf Miguel Malek 
Published: October 2021

PurposeThis study investigates the impact of a buyer-assisted quality intervention on suppliers' quality performance and buyer–supplier relational dynamics in the garment industry.Design/methodology/approachThis study employed a multiple-embedded case study following a qualitative research approach. The study used data from buyer-assisted quality interventions in sewing lines of four garment supplier factories. Qualitative data were collected through semi-structured interviews of buyer's representatives at their office and senior managers, line inspectors, supervisors and workers in supplier factories. In addition, data related to product quality was obtained from quality check sheets and observations on the shop floor. Data were analysed using qualitative data analysis techniques.FindingsThis study demonstrates that a buyer-assisted quality intervention improves product quality performance by reducing quality defects in targeted garment products resulting in improved buyer–supplier relationships. Moreover, this study identifies the lack of a systematic approach in quality control as a key reason for poor product quality.Research limitations/implicationsThe study adds knowledge to the literature on quality improvement and buyer–supplier relationships by analysing buyer-assisted quality interventions in the garment industry in Bangladesh. The study demonstrates that buyer's assistance and adopting a systematic approach in quality control can significantly improve product quality in the garment industry.Practical implicationsThis research can help the quality assurance managers in buyer and supplier firms understand the significance of quality interventions and systematic quality control approach to decrease product quality defects and ensure smooth buyer–supplier relationships.Originality/valueThe study adds new knowledge on the link between buyer-assisted quality interventions, systematic quality control and product quality in garments factories in Bangladesh.
Improving competitiveness in education institutes – ABC’s neglected potential
Authors: Sorros John , Lois Petros , Charitou Melita , Karagiorgos Alkiviadis Theofanis , Belesis Nicholas 
Published: October 2021

PurposeBecause of the education sector’s evolution, accounting initiatives are required regarding competitiveness. Activity-based costing’s (ABC) neglected potential as a cost strategic tool initiated this research, which aims to identify administrative and operational factors that support or hinder its implementation in educational institutions as a predictor of competitiveness.Design/methodology/approachA theoretical model was proposed and tested through structural equation modeling to identify relationships between accounting departments, cost procedures, the transmissibility of information and competitiveness. Using quantitative and qualitative methods, a scale of items was derived, denoting an institute’s cost strategy and ABC implementations and returned from 417 Greek education institutes.FindingsAn accounting department’s role in accurate data transmissibility and an institution’s organizational structure significantly affect cost-related competitiveness. The importance of information sharing is strengthened by current cost allocation capabilities and the accounting department’s influence on management.Research limitations/implicationsABC’s limited implementation in the Greek education sector complicated the theoretical model’s construction, as a variety of geographical and institutional factors were taken into consideration.Practical implicationsCustomer value provides a competitive advantage and constitutes the basis of solid price strategies. Research demonstrates ABC’s importance for education institutions’ competitiveness and resource exploitation.Social implicationsEducation’s commercialization urges costing strategy prioritization. ABC could benefit competitiveness and attract long-term funds and investments. To create value institutions, the allocation of incurred costs to added-value activities is crucial.Originality/valueThis study sheds light on vague issues institutions face when dealing with ABC. Understanding accounting departments’ influence shows ABC’s feasibility even for smaller or less efficiency-oriented education institutions.