bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel psoralen derivatives as anti-breast cancer agents and their light-activated cytotoxicity against HER2 positive breast cancer cells
Authors: Aekrungrueangkit Chiphada , Wangngae Sirilak , Kamkaew Anyanee , Ardkhean Ruchuta , Thongnest Sanit , Boonsombat Jutatip , Ruchirawat Somsak , Khotavivattana Tanatorn 
Published: August 2022

AbstractPsoralen derivatives are well known for their unique phototoxicity and also exhibits promising anti-breast cancer activity both in the presence and the absence of UVA irradiation. However, the structure–activity relationship on this scaffold remains lacking. Herein, a series of psoralen derivatives with various C-5 substituents were synthesized and evaluated for their in vitro dark and light-activated cytotoxicity against three breast cancer cell lines: MDA-MB-231, T47-D, and SK-BR-3. The type of substituents dramatically impacted the activity, with the 4-bromobenzyl amide derivative (3c) exhibiting the highest dark cytotoxicity against T47-D (IC50 = 10.14 µM), with the activity comparable to those of the reference drugs (doxorubicin, 1.46 µM; tamoxifen citrate, 20.86 µM; lapatinib 9.78 µM). On the other hand, the furanylamide 3g exhibits the highest phototoxicity against SK-BR-3 cells with the IC50 of 2.71 µM, which is almost tenfold increase compared to the parent compound, methoxsalen. Moreover, these derivatives showed exceptional selectivity towards HER2+ (SK-BR-3) over the HER2− (MDA-MB-231) breast cancer cell lines, which correlates well with the results from the molecular docking study, revealing that 3g formed favorable interactions within the active site of the HER2. Additionally, the cell morphology of SK-BR-3 cells suggested that the significant phototoxicity was related to induction of cell apoptosis. Most of the synthesized psoralen derivatives possess acceptable physicochemical properties and are suitable for being further developed as a novel anti-breast cancer agent in the future.
Modelling pandemic behaviour using an economic multiplayer game
Authors: van Baal Simon T. , Walasek Lukasz , Hohwy Jakob 
Published: August 2022

AbstractDuring a pandemic, isolating oneself from the community limits viral transmission and helps avoid repeated societal lockdowns. This entails a social dilemma—either distance oneself from others for the benefit of the public good or free-ride and enjoy the benefits of freedom. It is not yet understood how the unfamiliar incentive structure and interpersonal context presented by a pandemic together modulate individuals’ approach to this social dilemma. In this preregistered study, we take a game-theoretical approach and investigate people’s decisions to self-isolate, using a novel iterated multiplayer game designed to capture the decision-making environment in the pandemic. To elucidate players’ thinking, we use a variation of the strategy method and elicit beliefs about how much others will self-isolate. Players tend to respond to social norms with abidance, rather than transgression; they resist the temptation to freeride when others are self-isolating. However, they deal with exponential growth poorly, as they only self-isolate sufficiently when lockdowns are imminent. Further, increased collective risk can motivate more self-isolation, even though the link between self-isolation and lockdowns is stochastic. Players underreport the influence of others’ choices on their own, and underestimate others’ self-isolation. We discuss implications for public health, and communication to the public.
Auxetic structures used in kinesiology tapes can improve form-fitting and personalization
Authors: Meeusen Luna , Candidori Sara , Micoli Laura Loredana , Guidi Gabriele , Stanković Tino , Graziosi Serena 
Published: August 2022

AbstractEach year 65% of young athletes and 25% of physically active adults suffer from at least one musculoskeletal injury that prevents them from continuing with physical activity, negatively influencing their physical and mental well-being. The treatment of musculoskeletal injuries with the adhesive elastic kinesiology tape (KT) decreases the recovery time. Patients can thus recommence physical exercise earlier. Here, a novel KT based on auxetic structures is proposed to simplify the application procedure and allow personalization. This novel KT exploits the form-fitting property of auxetics as well as their ability to simultaneously expand in two perpendicular directions when stretched. The auxetic contribution is tuned by optimizing the structure design using analytical equations and experimental measurements. A reentrant honeycomb topology is selected to demonstrate the validity of the proposed approach. Prototypes of auxetic KT to treat general elbow pains and muscle tenseness in the forearm are developed.
Thermospheric parameters contribution to the formation of Yakutsk F2-layer diurnal summer time anomaly
Authors: Mikhailov Andrey V. , Perrone Loredana 
Published: August 2022

AbstractThe role of thermospheric neutral composition in the formation of the Yakutsk diurnal summer time foF2anomaly is analyzed. Ionospheric stations inside and outside the anomaly area are considered. The effect of neutral composition in foF2is the most noticeable around noontime hours. The difference between observed noontime foF2in two areas is significant at the 99.9% confidence level both for monthly median and individual days. The inferred from ionosonde observations and Swarm neutral gas density thermospheric parameters indicate a significant difference between two areas. The inferred exospheric temperature, Tex at Magadan (inside the anomaly area) is significantly larger than Tex at Tunguska (outside the anomaly area). On the contrary, the inferred atomic oxygen [O] at Tunguska is significantly larger than at Magadan. Different [O] abundance in the two areas is the main reason of the observed difference in noontime foF2values. Vertical plasma drift depending on magnetic declination, D is the only process responsible for the difference between nighttime foF2at Tunguska and Magadan. A possible mechanism of the revealed difference in thermospheric parameters inside and outside the anomaly area is discussed.
Detection and molecular characterization of Avipoxvirus in Culex spp. (Culicidae) captured in domestic areas in Rio de Janeiro, Brazil
Authors: van der Meer Carolina Soares , Paulino Patrícia Gonzaga , Jardim Talys Henrique Assumpção , Senne Nathália Alves , Araujo Thamires Rezende , dos Santos Juliano Daniele , Massard Carlos Luiz , Peixoto Maristela Peckle , da Costa Angelo Isabele , Santos Huarrisson Azevedo 
Published: August 2022

AbstractAvian pox is a highly contagious poultry disease that causes significant economic losses. Mosquitoes belonging to the genus Culex (Diptera: Culicidae) have a fundamental role in disseminating Avipoxvirus (Poxviridae). This study proposes investigating the presence of Avipoxvirus (APV) DNA in Culex spp. from Rio de Janeiro to determine its frequency and perform a phylogenetic analysis based on the core like the 4b protein (p4b) gene. The detection of APVs was conducted individually on four hundred Culex spp. mosquitoes. A total of 12.23% (47/384) of the Culex spp. were positive in the PCR. Sequencing the p4b gene revealed that this study’s sequences displayed 98.8–99% identity with Fowlpoxvirus (FWPW) sequences available in GenBank. In the phylogenetic analysis, these APVs were clustered in the A1 subclade together with FWPW sequences from several countries. The evolutionary distance of the p4b gene was 0.61 ± 0.21% in rural areas and 0.38 ± 0.16% in peri-urban areas. The current investigation is the first study to report the detection of APVs in field-caught mosquitoes. Moreover, a high frequency of APV DNA was observed in Culex spp. captured in domestic areas, where backyard poultry is present. This data demonstrates the importance of implementing control measures for Culex spp. to mitigate the transmission of APVs in backyard poultry in Rio de Janeiro.
Enhancing nanoparticle accumulation in two dimensional, three dimensional, and xenograft mouse cancer cell models in the presence of docetaxel
Authors: Bromma Kyle , Dos Santos Nancy , Barta Ingrid , Alexander Abraham , Beckham Wayne , Krishnan Sunil , Chithrani Devika B. 
Published: August 2022

AbstractRecent clinical trials show docetaxel (DTX), given in conjunction with radiation therapy (RT) and androgen suppression, improves survival in high-risk prostate cancer. Addition of gold nanoparticles (GNPs) to this current DTX/RT protocol is expected to further improve therapeutic benefits remarkably. However, the foundation for the triple combination of RT, DTX, and GNPs must be elucidated to ensure quicker facilitation to the clinic. In this study, we explored the use of low concentrations of DTX combined with GNPs in two prostate cancer cell lines in a two-dimensional monolayer, a three-dimensional spheroid, and a mouse xenograft model. When used together, DTX and GNPs induced a nearly identical relative increase in uptake of gold in both the spheroid model and the mouse xenograft, which saw a 130% and 126% increase respectively after 24 h, showcasing the benefit of using spheroids as an in vitro model to better optimize in vivo experiments. Further, the benefits of using low concentrations of DTX combined with GNPs extended for over 72 h, allowing for less frequency in dosing when translating to the clinic. Overall, these results highlight the benefits of using DTX combined with GNPs and lays the groundwork for the translation of the triple combination of RT, GNPs, and DTX to the clinic.
A multiomics disease progression signature of low-risk ccRCC
Authors: Strauss Philipp , Rivedal Mariell , Scherer Andreas , Eikrem Øystein , Nakken Sigrid , Beisland Christian , Bostad Leif , Flatberg Arnar , Skandalou Eleni , Beisvåg Vidar , Furriol Jessica , Marti Hans-Peter 
Published: August 2022

AbstractClear cell renal cell carcinoma (ccRCC) is the most common renal cancer. Identification of ccRCC likely to progress, despite an apparent low risk at the time of surgery, represents a key clinical issue. From a cohort of adult ccRCC patients (n = 443), we selected low-risk tumors progressing within a 5-years average follow-up (progressors: P, n = 8) and non-progressing (NP) tumors (n = 16). Transcriptome sequencing, miRNA sequencing and proteomics were performed on tissues obtained at surgery. We identified 151 proteins, 1167 mRNAs and 63 miRNAs differentially expressed in P compared to NP low-risk tumors. Pathway analysis demonstrated overrepresentation of proteins related to “LXR/RXR and FXR/RXR Activation”, “Acute Phase Response Signaling” in NP compared to P samples. Integrating mRNA, miRNA and proteomic data, we developed a 10-component classifier including two proteins, three genes and five miRNAs, effectively differentiating P and NP ccRCC and capturing underlying biological differences, potentially useful to identify “low-risk” patients requiring closer surveillance and treatment adjustments. Key results were validated by immunohistochemistry, qPCR and data from publicly available databases. Our work suggests that LXR, FXR and macrophage activation pathways could be critically involved in the inhibition of the progression of low-risk ccRCC. Furthermore, a 10-component classifier could support an early identification of apparently low-risk ccRCC patients.
Allele-biased expression of the bovine APOB gene associated with the cholesterol deficiency defect suggests cis-regulatory enhancer effects of the LTR retrotransposon insertion
Authors: Becker Doreen , Weikard Rosemarie , Heimes Annika , Hadlich Frieder , Hammon Harald M. , Meyerholz Marie M. , Petzl Wolfram , Zerbe Holm , Schuberth Hans-Joachim , Hoedemaker Martina , Schmicke Marion , Engelmann Susanne , Kühn Christa 
Published: August 2022

AbstractThe insertion of an endogenous retroviral long terminal repeat (LTR) sequence into the bovine apolipoprotein B (APOB) gene is causal to the inherited genetic defect cholesterol deficiency (CD) observed in neonatal and young calves. Affected calves suffer from developmental abnormalities, symptoms of incurable diarrhoea and often die within weeks to a few months after birth. Neither the detailed effects of the LTR insertion on APOB expression profile nor the specific mode of inheritance nor detailed phenotypic consequences of the mutation are undisputed. In our study, we analysed German Holstein dairy heifers at the peak of hepatic metabolic load and exposed to an additional pathogen challenge for clinical, metabolic and hepatic transcriptome differences between wild type (CDF) and heterozygote carriers of the mutation (CDC). Our data revealed that a divergent allele-biased expression pattern of the APOB gene in heterozygous CDC animals leads to a tenfold higher expression of exons upstream and a decreased expression of exons downstream of the LTR insertion compared to expression levels of CDF animals. This expression pattern could be a result of enhancer activity induced by the LTR insertion, in addition to a previously reported artificial polyadenylation signal. Thus, our data support a regulatory potential of mobile element insertions. With regard to the phenotype generated by the LTR insertion, heterozygote CDC carriers display significantly differential hepatic expression of genes involved in cholesterol biosynthesis and lipid metabolism. Phenotypically, CDC carriers show a significantly affected lipomobilization compared to wild type animals. These results reject a completely recessive mode of inheritance for the CD defect, which should be considered for selection decisions in the affected population. Exemplarily, our results illustrate the regulatory impact of mobile element insertions not only on specific host target gene expression but also on global transcriptome profiles with subsequent biological, functional and phenotypic consequences in a natural in-vivo model of a non-model mammalian organism.
Pharmacokinetic and metabolomic studies with a BIO 300 Oral Powder formulation in nonhuman primates
Authors: Li Yaoxiang , Girgis Michael , Jayatilake Meth , Serebrenik Artur A. , Cheema Amrita K. , Kaytor Michael D. , Singh Vijay K. 
Published: August 2022

AbstractBIO 300, a pharmaceutical formulation of genistein, is being developed as a radiation countermeasure to treat hematopoietic acute radiation syndrome (H-ARS) and the delayed effects of acute radiation exposure (DEARE). Several studies have affirmed its safety and efficacy in alleviating the damaging effects of ionizing radiation. However, dose optimization of any drug has always been an important area of research because unnecessarily high drug doses may result in serious complications. In this study, we assessed the pharmacokinetics (PK) and metabolic profiles of two different doses of a novel solid-dosage formulation of BIO 300 (BIO 300 Oral Powder; 100 mg/kg and 200 mg/kg), when administered orally to nonhuman primates (NHPs). While the Tmax values of both doses remained the same, the area under the curve at 48 h (AUC0-48) was tripled by doubling the dose. Additionally, we monitored serum samples for global metabolomic/lipidomic changes using high resolution mass spectrometry followed by functional pathway analysis prior to and at various time points up to 48 h post drug administration. Interestingly, the metabolomic profiles of sera from NHPs that received the lower dose demonstrated a transient perturbation in numerous metabolites between the 4 and 12 h time points. Eventually, the metabolite abundance reverted to near-normal by 48 h. These study results are consistent with our previous studies focused on the PK and metabolomic analysis for parenteral and oral aqueous nanosuspension formulations of BIO 300. This study affirms that administration of a single dose of up to 200 mg/kg of BIO 300 Oral Powder is safe in NHPs and conferred no metabolomic-mediated safety features.
Primary CNS vasculitis (PCNSV): a cohort study
Authors: Agarwal Ayush , Sharma Jyoti , Srivastava M. V. Padma , Sharma M. C. , Bhatia Rohit , Dash Deepa , Goyal Vinay , Srivastava Achal K. , Tripathi Manjari , Suri Vaishali , Singh Mamta B. , Agarwal Sushant , Sarkar Chitra , Joseph Leve , Singh Manmohan , Suri Ashish , Singh Rajesh K. , Vibha Deepti , Pandit Awadh K. , Rajan Roopa , Gupta Anu , Elavarasi A. , Radhakrishnan Divya M. , Das Animesh , Gaikwad Shailesh , Tandon Vivek , Doddamani Ramesh , Upadhyay Ashish , Garg Ajay , Vishnu Venugopalan Y. 
Published: August 2022

AbstractPrimary CNS Vasculitis (PCNSV) is a rare inflammatory disorder affecting the blood vessels of the central nervous system. Patients present with a combination of headaches, seizures, and focal neurological deficits. There is usually a diagnostic delay. Treatment is based on observational studies and expert opinion. Our objective was to identify clinical, laboratory, neuroimaging, pathologic or management-related associations with 2 year outcome in patients with primary CNS vasculitis. We conducted a cohort study at a single tertiary care referral centre of prospectively (2018-2019) and retrospectively (2010-2018) identified individuals with primary CNS vasculitis (diagnosis was proven by either brain biopsy or cerebral digital subtraction angiography). Clinical, imaging and histopathologic findings, treatment, and functional outcomes were recorded. Univariate and stepwise multiple logistic regression were applied. P-value<0.05 was considered statistically significant. The main outcome measures were documentation of clinical improvement or worsening (defined by mRS scores) and identification of independent predictors of good functional outcome (mRS 0-2) at 2 years. We enrolled eighty-two biopsy and/or angiographically proven PCNSV cases. The median age at presentation was 34 years with a male predilection and a median diagnostic delay of 23 months. Most patients presented with seizures (70.7%). All patients had haemorrhages on MRI. Histologically lymphocytic subtype was the commonest. Corticosteroids with cyclophosphamide was the commonest medication used. The median mRS at follow-up of 2 years was 2 (0-3), and 65.2% of patients achieved a good functional outcome. Myelitis and longer duration of illness before diagnosis were associated with poorer outcomes. The presence of hemorrhages on SWI sequence of MRI might be a sensitive imaging marker. Treatment with steroids and another immunosuppressant probably reduced relapse rates in our cohort. We have described the third largest PCNSV cohort and multi-centre randomised controlled trials are required to study the relative efficacy of various immunosuppressants.Study registration: CTRI/2018/03/012721.
Lombard Effect in Individuals With Nonphonotraumatic Vocal Hyperfunction: Impact on Acoustic, Aerodynamic, and Vocal Fold Vibratory Parameters
Authors: Castro Christian , Prado Pavel , Espinoza Víctor M. , Testart Alba , Marfull Daphne , Manriquez Rodrigo , Stepp Cara E. , Mehta Daryush D. , Hillman Robert E. , Zañartu Matías 
Published: August 2022

Purpose:
This exploratory study aims to investigate variations in voice production in the presence of background noise (Lombard effect) in individuals with nonphonotraumatic vocal hyperfunction (NPVH) and individuals with typical voices using acoustic, aerodynamic, and vocal fold vibratory measures of phonatory function.

Method:
Nineteen participants with NPVH and 19 participants with typical voices produced simple vocal tasks in three sequential background conditions: baseline (in quiet), Lombard (in noise), and recovery (5 min after removing the noise). The Lombard condition consisted of speech-shaped noise at 80 dB SPL through audiometric headphones. Acoustic measures from a microphone, glottal aerodynamic parameters estimated from the oral airflow measured with a circumferentially vented pneumotachograph mask, and vocal fold vibratory parameters from high-speed videoendoscopy were analyzed.

Results:
During the Lombard condition, both groups exhibited a decrease in open quotient and increases in sound pressure level, peak-to-peak glottal airflow, maximum flow declination rate, and subglottal pressure. During the recovery condition, the acoustic and aerodynamic measures of individuals with typical voices returned to those of the baseline condition; however, recovery measures for individuals with NPVH did not return to baseline values.

Conclusions:
As expected, individuals with NPVH and participants with typical voices exhibited a Lombard effect in the presence of elevated background noise levels. During the recovery condition, individuals with NPVH did not return to their baseline state, pointing to a persistence of the Lombard effect after noise removal. This behavior could be related to disruptions in laryngeal motor control and may play a role in the etiology of NPVH.

Supplemental Material:

https://doi.org/10.23641/asha.20415600
Recursive recurrent neural network: A novel model for manipulator control with different levels of physical constraints
Authors: Li Zhan , Li Shuai 
Published: August 2022

AbstractManipulators actuate joints to let end effectors to perform precise path tracking tasks. Recurrent neural network which is described by dynamic models with parallel processing capability, is a powerful tool for kinematic control of manipulators. Due to physical limitations and actuation saturation of manipulator joints, the involvement of joint constraints for kinematic control of manipulators is essential and critical. However, current existing manipulator control methods based on recurrent neural networks mainly handle with limited levels of joint angular constraints, and to the best of our knowledge, methods for kinematic control of manipulators with higher order joint constraints based on recurrent neural networks are not yet reported. In this study, for the first time, a novel recursive recurrent network model is proposed to solve the kinematic control issue for manipulators with different levels of physical constraints, and the proposed recursive recurrent neural network can be formulated as a new manifold system to ensure control solution within all of the joint constraints in different orders. The theoretical analysis shows the stability and the purposed recursive recurrent neural network and its convergence to solution. Simulation results further demonstrate the effectiveness of the proposed method in end‐effector path tracking control under different levels of joint constraints based on the Kuka manipulator system. Comparisons with other methods such as the pseudoinverse‐based method and conventional recurrent neural network method substantiate the superiority of the proposed method.
Elastic temporal alignment for few‐shot action recognition
Authors: Pan Fei , Xu Chunlei , Zhang Hongjie , Guo Jie , Guo Yanwen 
Published: August 2022

AbstractFew‐shot action recognition aims to learn a classification model with good generalisation ability when trained with only a few labelled videos. However, it is difficult to learn discriminative feature representations for videos in such a setting. The Elastic Temporal Alignment (ETA) for few‐shot action recognition is proposed. First, a convolutional neural network is employed to extract feature representations of video frames sparsely sampled from videos. In order to obtain the similarity of two videos, a temporal alignment estimation function is utilised to estimate the matching score between each pair of frames from the two videos through an elastic alignment mechanism. The analysis shows that when we judge whether two frames from respective videos are matched, multiple adjacent frames in the videos should be considered, so as to embody the temporal information. Thus, before feeding per‐frame feature vectors of videos into the temporal alignment estimation function, a temporal message passing function is leveraged to propagate the information of per‐frame features in the temporal domain. The method has been evaluated on four action recognition datasets, including Kinetics, Something‐Something V2, HMDB51, and UCF101. The experimental results verify the effectiveness of ETA and show its superiority over state‐of‐the‐art methods.