bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sorafenib and nitazoxanide disrupt mitochondrial function and inhibit regrowth capacity in three-dimensional models of hepatocellular and colorectal carcinoma
Authors: Ek Frida , Blom Kristin , Selvin Tove , Rudfeldt Jakob , Andersson Claes , Senkowski Wojciech , Brechot Christian , Nygren Peter , Larsson Rolf , Jarvius Malin , Fryknäs Mårten 
Published: May 2022

AbstractQuiescent cancer cells in malignant tumors can withstand cell-cycle active treatment and cause cancer spread and recurrence. Three-dimensional (3D) cancer cell models have led to the identification of oxidative phosphorylation (OXPHOS) as a context-dependent vulnerability. The limited treatment options for advanced hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) metastatic to the liver include the multikinase inhibitors sorafenib and regorafenib. Off-target effects of sorafenib and regorafenib are related to OXPHOS inhibition; however the importance of this feature to the effect on tumor cells has not been investigated in 3D models. We began by assessing global transcriptional responses in monolayer cell cultures, then moved on to multicellular tumor spheroids (MCTS) and tumoroids generated from a CRC patient. Cells were treated with chemotherapeutics, kinase inhibitors, and the OXPHOS inhibitors. Cells grown in 3D cultures were sensitive to the OXPHOS inhibitor nitazoxanide, sorafenib, and regorafenib and resistant to other multikinase inhibitors and chemotherapeutic drugs. Furthermore, nitazoxanide and sorafenib reduced viability, regrowth potential and inhibited mitochondrial membrane potential in an additive manner at clinically relevant concentrations. This study demonstrates that the OXPHOS inhibition caused by sorafenib and regorafenib parallels 3D activity and can be further investigated for new combination strategies.
Polyploid giant cancer cells are dependent on cholesterol for progeny formation through amitotic division
Authors: White-Gilbertson Shai , Lu Ping , Esobi Ikechukwu , Echesabal-Chen Jing , Mulholland Patrick J. , Gooz Monika , Ogretmen Besim , Stamatikos Alexis , Voelkel-Johnson Christina 
Published: May 2022

AbstractPolyploid Giant Cancer Cells (PGCC) are increasingly being recognized as drivers of cancer recurrence. Therapy stress promotes the formation of these cells, which upon stress cessation often successfully generate more aggressive progeny that repopulate the tumor. Therefore, identification of potential PGCC vulnerabilities is key to preventing therapy failure. We have previously demonstrated that PGCC progeny formation depends on the lysosomal enzyme acid ceramidase (ASAH1). In this study, we compared transcriptomes of parental cancer cells and PGCC in the absence or presence of the ASAH1 inhibitor LCL521. Results show that PGCC express less INSIG1, which downregulates cholesterol metabolism and that inhibition of ASAH1 increased HMGCR which is the rate limiting enzyme in cholesterol synthesis. Confocal microscopy revealed that ceramide and cholesterol do not colocalize. Treatment with LCL521 or simvastatin to inhibit ASAH1 or HMGCR, respectively, resulted in accumulation of ceramide at the cell surface of PGCC and prevented PGCC progeny formation. Our results suggest that similarly to inhibition of ASAH1, disruption of cholesterol signaling is a potential strategy to interfere with PGCC progeny formation.
Economic and social deprivation predicts impulsive choice in children
Authors: Tunney Richard J. 
Published: May 2022

AbstractImpulsivity is an individual difference in decision-making that is a risk factor for a number of health concerns including addiction and obesity. Although impulsivity has a large heritable component, the health concerns associated with impulsivity are not uniformly distributed across society. For example, people from poorer backgrounds are more likely to be overweight, and be dependent on tobacco or alcohol. This suggests that the environmental component of impulsivity might be related to economic circumstances and the availability of resources. This paper provides evidence that children aged 4 to 12 from the most deprived areas in England show greater impulsivity in the form of delay discounting than do children from the least deprived areas. The data are discussed with reference to scarcity-based models of decision-making and to public health inequalities.
Energy and thermal modelling of an office building to develop an artificial neural networks model
Authors: Santos-Herrero Jose Maria , Lopez-Guede Jose Manuel , Flores Abascal Ivan , Zulueta Ekaitz 
Published: May 2022

AbstractNowadays everyone should be aware of the importance of reducing CO2 emissions which produce the greenhouse effect. In the field of construction, several options are proposed to reach nearly-Zero Energy Building (nZEB) standards. Obviously, before undertaking a modification in any part of a building focused on improving the energy performance, it is generally better to carry out simulations to evaluate its effectiveness. Using Artificial Neural Networks (ANNs) allows a digital twin of the building to be obtained for specific characteristics without using very expensive software. This can simulate the effect of a single or combined intervention on a particular floor or an event on the remaining floors. In this paper, an example has been developed based on ANN. The results show a reasonable correlation between the real data of the Operative Temperature with the Energy Consumption and their estimates obtained through an ANN model, trained using an hourly basis, on each of the floors of an office building. This model confirms it is possible to obtain simulations in existing public buildings with an acceptable degree of precision and without laborious modelling, which would make it easier to achieve the nZEB target, especially in existing public office buildings.
Biogenic silver/silver chloride nanoparticles inhibit human cancer cells proliferation in vitro and Ehrlich ascites carcinoma cells growth in vivo
Authors: Kabir Syed Rashel , Islam Farhadul , Asaduzzaman A. K. M. 
Published: May 2022

AbstractSilver/silver chloride nanoparticles (Ag/AgCl-NPs) were synthesized for the first time from the herbal Geodorum densiflorum rhizome extracts and characterized by different techniques. The surface plasmon resonance peak at 455 nm was observed in the UV–Visible spectrum, the average particle size of 25 nm was determined by SEM, XRD reflection peaks (28.00°, 32.42°, 38.28°, 46.38°, 54.94°, 57.60°, 64.64°, and 67.48°) indicated the presence of Ag-NPs and AgCl-NPs, heat stability was confirmed by TGA and FTIR analysis indicated the presence of alcohol/phenol, alkanes, primary amines, nitro compounds, alkyl chloride functional groups. The synthesized Ag/AgCl-NPs, previously synthesized Kaempferia rotunda and Zizyphus mauritiana mediated Ag/AgCl-NPs separately inhibited the proliferation of BxPC-3 cells with the IC50 values of 7.8, 17.1, and 20.1 µg/ml, respectively. In the case of MCF-7 cells, the IC50 values of G. densiflorum- Ag/AgCl-NPs and K. rotunda-Ag/AgCl-NPs were 21.5 and 23.5 µg/ml, respectively. Whereas the IC50 of G. densiflorum-Ag/AgCl-NPs was 28.0 µg/ml against glioblastoma stem cells (GSCs). Induction of apoptosis in GSCs, BxPC-3 and MCF-7 cells was noted followed by NPs treatment. In GSCs, the expression level of NFκB, TNFα, p21, and TLR9 genes were upregulated after treatment with G. densiflorum-Ag/AgCl-NPs while in the MCF-7 cells, the expression of p53, FAS, Caspase-8 and -9, NFκB, MAPK, JNK and p21 genes were increased. G. densiflorum-Ag/AgCl-NPs inhibited 60% and 95% of EAC cells growth at the doses of 2 and 4 mg/Kg/day after intraperitoneal treatment with five consequent days, respectively. A remarkable improvement of hematological parameters with the decreased average tumor weight and increase of 75% life span of G. densiflorum-Ag/AgCl-NPs treated mice were observed. Altogether, this study reported for the first time in vitro anticancer activity of biogenic G. densiflorum-Ag/AgCl-NPs against GSC cells along with MCF-7 and BxPC-3 cells and in vivo anticancer properties against EAC cells.
LCA and negative emission potential of retrofitted cement plants under oxyfuel conditions at high biogenic fuel shares
Authors: Cavalett Otavio , Watanabe Marcos D. B. , Fleiger Kristina , Hoenig Volker , Cherubini Francesco 
Published: May 2022

AbstractThe implementation of oxyfuel carbon capture and storage technologies in combination with use of alternative fuels comprising high biogenic shares is promoted as an attractive climate change mitigation option for the cement sector to achieve low or even negative carbon emissions. Here, we perform a prospective life cycle assessment of two state-of-the art cement plants, one in Sweden and one in Germany, under conventional and retrofitted oxyfuel conditions considering alternative fuel mixes with increasing bio-based fractions of forest residues or dedicated bioenergy crops. The analysis also considers effects of the projected changes in the electricity systems up to 2050. Retrofitting the cement plants to oxyfuel reduces climate change impacts between 74 and 91%, while with additional use of biomass as alternative fuel the cement plants reach negative emission between − 24 and − 169 gCO2eq. kgclinker−1, depending on operational condition, location, and biomass type. Additional emission reduction of − 10 (Sweden) and − 128 gCO2eq. kgclinker−1 (Germany) are expected from the decarbonization of the future electricity systems. Retrofitting the cement plants to oxyfuel conditions shows trade-offs with other environmental impacts (e.g., human toxicity, water and energy depletion), which are partially offset with projected changes in electricity systems. Our results illustrate the large climate change mitigation potential in the cement sector that can be achieved by the implementation of oxyfuel carbon capture and storage and biomass use as alternative fuel.
Chromatin accessibility analysis reveals regulatory dynamics and therapeutic relevance of Vogt-Koyanagi-Harada disease
Authors: Shi Wen , Ye Jinguo , Shi Zhuoxing , Pan Caineng , Zhang Qikai , Lin Yuheng , Luo Yuanting , Su Wenru , Zheng Yingfeng , Liu Yizhi 
Published: May 2022

AbstractThe barrier to curing Vogt–Koyanagi–Harada disease (VKH) is thought to reside in a lack of understanding in the roles and regulations of peripheral inflammatory immune cells. Here we perform a single-cell multi-omic study of 166,149 cells in peripheral blood mononuclear cells from patients with VKH, profile the chromatin accessibility and gene expression in the same blood samples, and uncover prominent cellular heterogeneity. Immune cells in VKH blood are highly activated and pro-inflammatory. Notably, we describe an enrichment of transcription targets for nuclear factor kappa B in conventional dendritic cells (cDCs) that governed inflammation. Integrative analysis of transcriptomic and chromatin maps shows that the RELA in cDCs is related to disease complications and poor prognosis. Ligand-receptor interaction pairs also identify cDC as an important predictor that regulated multiple immune subsets. Our results reveal epigenetic and transcriptional dynamics in auto-inflammation, especially the cDC subtype that might lead to therapeutic strategies in VKH.
PepNN: a deep attention model for the identification of peptide binding sites
Authors: Abdin Osama , Nim Satra , Wen Han , Kim Philip M. 
Published: May 2022

AbstractProtein-peptide interactions play a fundamental role in many cellular processes, but remain underexplored experimentally and difficult to model computationally. Here, we present PepNN-Struct and PepNN-Seq, structure and sequence-based approaches for the prediction of peptide binding sites on a protein. A main difficulty for the prediction of peptide-protein interactions is the flexibility of peptides and their tendency to undergo conformational changes upon binding. Motivated by this, we developed reciprocal attention to simultaneously update the encodings of peptide and protein residues while enforcing symmetry, allowing for information flow between the two inputs. PepNN integrates this module with modern graph neural network layers and a series of transfer learning steps are used during training to compensate for the scarcity of peptide-protein complex information. We show that PepNN-Struct achieves consistently high performance across different benchmark datasets. We also show that PepNN makes reasonable peptide-agnostic predictions, allowing for the identification of novel peptide binding proteins.
The Streptomyces viridochromogenes product template domain represents an evolutionary intermediate between dehydratase and aldol cyclase of type I polyketide synthases
Authors: Feng Yuanyuan , Yang Xu , Ji Huining , Deng Zixin , Lin Shuangjun , Zheng Jianting 
Published: May 2022

AbstractThe product template (PT) domains act as an aldol cyclase to control the regiospecific aldol cyclization of the extremely reactive poly-β-ketone intermediate assembled by an iterative type I polyketide synthases (PKSs). Up to now, only the structure of fungal PksA PT that mediates the first-ring cyclization via C4–C9 aldol cyclization is available. We describe here the structural and computational characterization of a bacteria PT domain that controls C2–C7 cyclization in orsellinic acid (OSA) synthesis. Mutating the catalytic H949 of the PT abolishes production of OSA and results in a tetraacetic acid lactone (TTL) generated by spontaneous O-C cyclization of the acyl carrier protein (ACP)-bound tetraketide intermediate. Crystal structure of the bacterial PT domain closely resembles dehydrase (DH) domains of modular type I PKSs in the overall fold, dimerization interface and His-Asp catalytic dyad organization, but is significantly different from PTs of fungal iterative type I PKSs. QM/MM calculation suggests that the catalytic H949 abstracts a proton from C2 and transfers it to C7 carbonyl to mediate the cyclization reaction. According to structural similarity to DHs and functional similarity to fungal PTs, we propose that the bacterial PT represents an evolutionary intermediate between the two tailoring domains of type I PKSs.
Humanoid robots to mechanically stress human cells grown in soft bioreactors
Authors: Mouthuy Pierre-Alexis , Snelling Sarah , Hostettler Rafael , Kharchenko Alona , Salmon Sarah , Wainman Alan , Mimpen Jolet , Paul Claudia , Carr Andrew 
Published: May 2022

AbstractFor more than 20 years, robotic bioreactor systems have facilitated the growth of tissue-engineered constructs using mechanical stimulation. However, we are still unable to produce functional grafts that can translate into clinical use. Humanoid robots offer the prospect of providing physiologically-relevant mechanical stimulation to grafts and implants which may expedite their clinical deployment. To investigate the feasibility of a humanoid bioreactor, we have designed a flexible bioreactor chamber that can be attached to a modified musculoskeletal (MSK) humanoid robot shoulder joint. We demonstrate that fibroblast cells can be grown in this chamber while undergoing physiological adduction-abduction on the robotic arm. A preliminary evaluation of the transcriptome of the cells after 14 days indicated a clear influence of the loading regime on the gene expression profile. These early results will facilitate the exploration of MSK humanoid robots as a biomechanically more realistic platform for tissue engineering and biomaterial testing applications.
Perceptions of Preceptors and Audiology Students on Practicum During the COVID-19 Pandemic
Authors: Brand Devora , Zachai Noa , Vider Gitit , Adelman Cahtia 
Published: May 2022

Purpose:
The aim of this study was to assess the perceptions of audiology students and preceptors regarding changes in the practicum as a result of COVID-19.

Method:
This study was conducted during two different periods, with Internet questionnaires posted on social media forums. Preceptors and newly graduated clinicians were recruited in 2019 for a study prior to COVID-19, and students and preceptors were recruited for comparison during COVID-19. Four groups participated in this study: (a) 101 students who were enrolled in the second, third, or fourth year of an Israeli communication disorders Bachelor of Arts (BA) program during the pandemic; (b) 94 newly graduated audiologists with a BA degree from an Israeli communication disorders program granted in the last 3 years (before COVID-19); (c) 18 audiologist preceptors who supervised audiology practicum in an Israeli communication disorders BA programs (before COVID-19); and (d) 20 audiologist preceptors who, during COVID-19, were supervising an audiology practicum in Israel. Perceptions of the various groups were compared.

Results:
Although perceptions of preceptors and students regarding the practicum were revealed to be similar, perceptions of the practicum before COVID-19 underwent changes in the course of the pandemic. In evaluating the COVID-19 experience, both preceptors and students agreed that more hours of practicum were needed, as well as more variety in types of cases and exposure to varied placements.

Conclusion:
Academic programs and employers should consider implications of changes implemented in the practicum due to COVID-19, which can be addressed either in continuing education and/or by additional supervision in the future workplace.

Supplemental Material:

https://doi.org/10.23641/asha.19855639
Rhythm Perception, Speaking Rate Entrainment, and Conversational Quality: A Mediated Model
Authors: Wynn Camille J. , Barrett Tyson S. , Borrie Stephanie A. 
Published: May 2022

Purpose:
Acoustic–prosodic entrainment, defined as the tendency for individuals to modify their speech behaviors to more closely align with the behaviors of their conversation partner, plays an important role in successful interaction. From a mechanistic perspective, acoustic–prosodic entrainment is, by its very nature, a rhythmic activity. Accordingly, it is highly plausible that an individual's rhythm perception abilities play a role in their ability to successfully entrain. Here, we examine the impact of rhythm perception in speaking rate entrainment and subsequent conversational quality.

Method:
A round-robin paradigm was used to collect 90 dialogues from neurotypical adults. Additional assessments determined participants' rhythm perception abilities, social competence, and partner familiarity (i.e., whether the conversation partners knew each other prior to the interaction. Mediation analysis was used to examine the relationships between rhythm perception scores, speaking rate entrainment (using a measure of static local synchrony), and a measure of conversational success (i.e., conversational quality) based on third-party listener observations. Findings were compared to the same analysis with three additional predictive factors: participant gender, partner familiarity, and social competence.

Results:
Results revealed a relationship between rhythm perception and speaking rate entrainment. In unfamiliar conversation partners, there was a relationship between speaking rate entrainment and conversational quality. The relationships between entrainment and each of the three additional factors (i.e., gender, partner familiarity, and social competence) were nonsignificant.

Conclusions:
In unfamiliar conversation partners, better rhythm perception abilities were indicative of increased conversational quality mediated by higher levels of speaking rate entrainment. These results support theoretical postulations specifying rhythm perception abilities as a component of acoustic–prosodic entrainment, which, in turn, facilitates conversational success. Knowledge of this relationship contributes to the development of a causal framework for considering a mechanism by which rhythm perception deficits in clinical populations may impact conversational success.
Outage minimisation for two‐way piece‐wise and forward (PF) relaying with SWIPT based energy harvesting
Authors: Khodakhah Farnaz , Keshavarz‐Haddad Alireza , Jamshidi Ali 
Published: May 2022

AbstractSimultaneous wireless information power transfer with power splitting is a new technology for energy harvesting that splits the received signal into two streams with adjustable power levels for information decoding and energy saving. Traditionally, decode and forward (DF) and amplify and forward (AF) schemes are used for energy harvesting in three‐step two‐way relay networks (TWRNs). In this paper, piece‐wise and forward (PF) scheme are applied with power splitting for energy harvesting in TWRNs. In PF, the received signal from each source at relay is compared to an adaptive threshold, if the signal strength is above the threshold, the relay functions similar to DF scheme, otherwise, the relay transmits a particular combination of its received signals from the sources. Next, the outage performance of PF protocol in a three‐step TWRN is studied and optimal lossless energy saving (OLES) method are presented to minimise the outage probability by computing the optimum power splitting ratio. The simulation and analytical results indicate that the outage probability of PF can be significantly improved using OLES technique in comparison with other related relaying schemes. The results show that the outage probability of PF‐OLES is 13, 3, and lower than AF‐OLES, DF‐OLES, and DAPS [1], respectively.
An integrated approach of a field‐circuit coupling model and multi‐physics finite‐element simulation for analysing transient electromagnetic vibration of pump motors
Authors: Zhao Jin , Zhang Qing , Wei Xiaohan 
Published: May 2022

AbstractWe propose a method to investigate the generation mechanism of the transient vibration of a pump motor induced by electromagnetic (electromagnetic (EM)) forces. Compared with the steady vibration of a pump motor, the transient vibration characterised by a wider excitation frequency spectrum and larger instantaneous amplitude makes the vulnerable structure more easily exposed to potential damage. However, transient vibration of pump motor has not been analysed and verified before. Based on the fact that EM vibration dominates the vibration of pump motors, in this study, an approach which integrates the field‐circuit coupling method and multi‐physics finite‐element (finite‐element (FE)) simulation is proposed to estimate the structural response of pump motors under transient operating conditions. To determine the factors that determine the EM forces, an analytical model describing the transient interaction between the EM and the fluid torque is first created. It was revealed that the input voltage and slip rate are two key factors that affect the transient EM forces. Then, to quantitatively describe the transient EM forces governed by a specific control scheme during the start‐up process, a field–circuit coupling model embedding in the control scheme, electrical circuit model, motor FE model, and rotor dynamic model is established. This model allows the circuit equations, rotor dynamics equations, and magnetic field equations to be solved simultaneously. The transient EM forces obtained by the field–circuit coupling model provide excitation for the structural response calculation. Subsequently, a multi‐physics FE simulation, which takes a weak coupling strategy between the EM and structural dynamics fields, is utilised to link the different physical domains. Thus, the EM forces are transferred to a structural domain to compute the structural response by adopting a direct integration method. The integration approach developed in this study was verified on the pump motors in the main cooling units of ultra‐high voltage (UHV) converter stations. The trends of dominant components of simulated signals agree with the measured signals from the pump motors. This indicates that the proposed method can be widely applied for the transient vibration analysis and mitigation for pump motors.