bluuebunny/crossref_metadata_2025_split huggingface dataset:
Basal and IL-1β enhanced chondrocyte chemotactic activity on monocytes are co-dependent on both IKKα and IKKβ NF-κB activating kinases
Authors: Olivotto Eleonora , Minguzzi Manuela , D’Adamo Stefania , Astolfi Annalisa , Santi Spartaco , Uguccioni Mariagrazia , Marcu Kenneth B. , Borzì Rosa Maria 
Published: November 2021

AbstractIKKα and IKKβ are essential kinases for activating NF-κB transcription factors that regulate cellular differentiation and inflammation. By virtue of their small size, chemokines support the crosstalk between cartilage and other joint compartments and contribute to immune cell chemotaxis in osteoarthritis (OA). Here we employed shRNA retroviruses to stably and efficiently ablate the expression of each IKK in primary OA chondrocytes to determine their individual contributions for monocyte chemotaxis in response to chondrocyte conditioned media. Both IKKα and IKKβ KDs blunted both the monocyte chemotactic potential and the protein levels of CCL2/MCP-1, the chemokine with the highest concentration and the strongest association with monocyte chemotaxis. These findings were mirrored by gene expression analysis indicating that the lowest levels of CCL2/MCP-1 and other monocyte-active chemokines were in IKKαKD cells under both basal and IL-1β stimulated conditions. We find that in their response to IL-1β stimulation IKKαKD primary OA chondrocytes have reduced levels of phosphorylated NFkappaB p65pSer536 and H3pSer10. Confocal microscopy analysis revealed co-localized p65 and H3pSer10 nuclear signals in agreement with our findings that IKKαKD effectively blunts their basal level and IL-1β dependent increases. Our results suggest that IKKα could be a novel OA disease target.
Novel LysM motifs for antigen display on lactobacilli for mucosal immunization
Authors: Raya-Tonetti Fernanda , Müller Melisa , Sacur Jacinto , Kitazawa Haruki , Villena Julio , Vizoso-Pinto Maria Guadalupe 
Published: November 2021

AbstractWe characterized two LysM domains of Limosilactobacillus fermentum, belonging to proteins Acglu (GenBank: KPH22907.1) and Pgb (GenBank: KPH22047.1) and bacterium like particles (BLP) derived from the immunomodulatory strain Lacticaseibacillus rhamnosus IBL027 (BLPs027) as an antigen display platform. The fluorescence protein Venus fused to the novel LysM domains could bind to the peptidoglycan shell of lactobacilli and resisted harsh conditions such as high NaCl and urea concentrations. Acglu with five LysM domains was a better anchor than Pgb baring only one domain. Six-week-old BALB/c mice were nasally immunized with the complex Venus-Acglu-BLPs027 at days 0, 14 and 28. The levels of specific serum IgG, IgG1 and IgG2a and the levels of total immunoglobulins (IgT) and IgA in broncho-alveolar lavage (BAL) were evaluated ten days after the last boosting. Venus-Acglu-BLPs027, nasally administered, significantly increased specific BAL IgT and IgA, and serum IgG levels. In addition, spleen cells of mice immunized with Venus-Acglu-BLPs027 secreted TNF-α, IFN-γ and IL-4 when stimulated ex vivo in a dose-dependent manner. We constructed a Gateway compatible destination vector to easily fuse the selected LysM domain to proteins of interest for antigen display to develop mucosal subunit vaccines.
Association between antibiotics use and diabetes incidence in a nationally representative retrospective cohort among Koreans
Authors: Park Sun Jae , Park Young Jun , Chang Jooyoung , Choi Seulggie , Lee Gyeongsil , Son Joung Sik , Kim Kyae Hyung , Oh Yun Hwan , Park Sang Min 
Published: November 2021

AbstractNumerous studies have reported that antibiotics could lead to diabetes, even after adjusting for confounding variables. This study aimed to determine the causal relationship between antibiotics use and diabetes in a nationally representative cohort. This retrospective cohort study included adults aged 40 years or older who were enrolled in the Korean National Health Insurance Service-Health Screening Cohort. Antibiotic exposure was assessed from 2002 to 2005 and newly diagnosed diabetes mellitus was determined based on diagnostic codes and history of antidiabetic medication use from 2006 to 2015. Multivariate Cox proportional hazards model was used to assess the association between antibiotic use and diabetes incidence. The mean age of the 201,459 study subjects was 53.2 years. People who used antibiotics for 90 or more days had a higher risk of diabetes (adjusted hazard ratio [aHR] 1.16, 95% confidence interval [CI] 1.07–1.26) compared to non-users. Those who used five or more classes of antibiotics had a higher risk of diabetes than those who used one antibiotic class (aHR 1.14; 95% CI 1.06–1.23). The clear dose-dependent association between antibiotics and diabetes incidence supports the judicious use of antibiotics in the future.
TGF-β1 is involved in senescence-related pathways in glomerular endothelial cells via p16 translocation and p21 induction
Authors: Ueda Sayo , Tominaga Tatsuya , Ochi Arisa , Sakurai Akiko , Nishimura Kenji , Shibata Eriko , Wakino Shu , Tamaki Masanori , Nagai Kojiro 
Published: November 2021

Abstractp16 inhibits cyclin-dependent kinases and regulates senescence-mediated arrest as well as p21. Nuclear p16 promotes G1 cell cycle arrest and cellular senescence. In various glomerular diseases, nuclear p16 expression is associated with disease progression. Therefore, the location of p16 is important. However, the mechanism of p16 trafficking between the nucleus and cytoplasm is yet to be fully investigated. TGF-β1, a major cytokine involved in the development of kidney diseases, can upregulate p21 expression. However, the relationship between TGF-β1 and p16 is poorly understood. Here, we report the role of podocyte TGF-β1 in regulating the p16 behavior in glomerular endothelial cells. We analyzed podocyte-specific TGF-β1 overexpression mice. Although p16 was found in the nuclei of glomerular endothelial cells and led to endothelial cellular senescence, the expression of p16 did not increase in glomeruli. In cultured endothelial cells, TGF-β1 induced nuclear translocation of p16 without increasing its expression. Among human glomerular diseases, p16 was detected in the nuclei of glomerular endothelial cells. In summary, we demonstrated the novel role of podocyte TGF-β1 in managing p16 behavior and cellular senescence in glomeruli, which has clinical relevance for the progression of human glomerular diseases.
Silencing of vitellogenin gene contributes to the promise of controlling red palm weevil, Rhynchophorus ferrugineus (Olivier)
Authors: Rasool Khawaja G. , Mehmood Khalid , Tufail Muhammad , Husain Mureed , Alwaneen Waleed S. , Aldawood Abdulrahman S. 
Published: November 2021

AbstractRed palm weevil [Rhynchophorus ferrugineus (Olivier)], is native to South Asia and expanding its distribution range globally. Recent invasions of red palm weevil around the world, including Saudi Arabia, has become a global constraint for the production of palm species. Although, several control measures have been tested, none of them seemed successful against this invasive species. Therefore, we focused on silencing the reproduction control gene vitellogenin (Vg) based on RNA interference (RNAi) strategy for its possible application in the management of R. ferrugineus. The Vg is a major yolk protein precursor critical for oogenesis. To do this, fat body transcriptome of R. ferrugineus female adults was sequenced, which provided partial Vg gene transcript (FPKM 5731.60). A complete RfVg gene transcript of 5504 bp encoding 1787 amino acids was then sequenced using RCAE-PCR strategy and characterized. Phylogenetic analysis suggested that RfVg has closer ancestry to the coleopteran insects. The RfVg-based RNAi significantly suppressed the expressions of Vg gene. The 15, 20 and 25 days post-injection periods suppressed Vg expressions by 95, 96.6 and 99%, respectively. The suppressed Vg expressions resulted in the dramatic failure of Vg protein expression, which caused atrophied ovaries or no oogenesis and ultimately eggs were not hatched. These results suggest that knockdown of Vg gene involved in R. ferrugineus reproduction is a promising target for RNAi-based management of R. ferrugineus.
Annual assessment of the wastewater treatment capacity of the microalga Scenedesmus almeriensis and optimisation of operational conditions
Authors: Sánchez-Zurano Ana , Morillas-España Ainoa , Gómez-Serrano Cintia , Ciardi Martina , Acién Gabriel , Lafarga Tomás 
Published: November 2021

AbstractThe depth of the culture and the dilution rate have a striking effect on the biomass productivity and the nutrient recovery capacity of microalgal cultures. The combination of culture depth and dilution rate that allows to maximise the performance of the system depends on environmental conditions. In the current study, a response surface methodology was used to explore the relationship between the two most relevant operational conditions and the biomass productivity achieved in 8.3 m2 pilot-scale raceways operated using urban wastewater. Four polynomial models were developed, one for each season of the year. The software predicted biomass productivities of 12.3, 25.6, 32.7, and 18.9 g·m−2·day−1 in winter, spring, summer, and autumn, respectively. The models were further validated at pilot-scale with R2 values ranging within 0.81 and 0.91, depending on the season. Lower culture depths had the advantage of minimising nitrification and stripping but allow to process a lower volume of wastewater per surface area. Biomass productivity was higher at culture depths of 0.05 m, when compared to 0.12 and 0.20 m, while the optimal dilution rate was season-dependent. Results reported herein are useful for optimising the biomass productivity of raceway reactors located outdoors throughout the year.
The transcriptome of Balamuthia mandrillaris trophozoites for structure-guided drug design
Authors: Phan Isabelle Q. , Rice Christopher A. , Craig Justin , Noorai Rooksana E. , McDonald Jacquelyn R. , Subramanian Sandhya , Tillery Logan , Barrett Lynn K. , Shankar Vijay , Morris James C. , Van Voorhis Wesley C. , Kyle Dennis E. , Myler Peter J. 
Published: November 2021

AbstractBalamuthia mandrillaris, a pathogenic free-living amoeba, causes cutaneous skin lesions as well as granulomatous amoebic encephalitis, a ‘brain-eating’ disease. As with the other known pathogenic free-living amoebas (Naegleria fowleri and Acanthamoeba species), drug discovery efforts to combat Balamuthia infections of the central nervous system are sparse; few targets have been validated or characterized at the molecular level, and little is known about the biochemical pathways necessary for parasite survival. Current treatments of encephalitis due to B. mandrillaris lack efficacy, leading to case fatality rates above 90%. Using our recently published methodology to discover potential drugs against pathogenic amoebas, we screened a collection of 85 compounds with known antiparasitic activity and identified 59 compounds that impacted the growth of Balamuthia trophozoites at concentrations below 220 µM. Since there is no fully annotated genome or proteome of B. mandrillaris, we sequenced and assembled its transcriptome from a high-throughput RNA-sequencing (RNA-Seq) experiment and located the coding sequences of the genes potentially targeted by the growth inhibitors from our compound screens. We determined the sequence of 17 of these target genes and obtained expression clones for 15 that we validated by direct sequencing. These will be used in the future in combination with the identified hits in structure guided drug discovery campaigns to develop new approaches for the treatment of Balamuthia infections.
A large Canadian cohort provides insights into the genetic architecture of human hair colour
Authors: Lona-Durazo Frida , Mendes Marla , Thakur Rohit , Funderburk Karen , Zhang Tongwu , Kovacs Michael A. , Choi Jiyeon , Brown Kevin M. , Parra Esteban J. 
Published: November 2021

AbstractHair colour is a polygenic phenotype that results from differences in the amount and ratio of melanins located in the hair bulb. Genome-wide association studies (GWAS) have identified many loci involved in the pigmentation pathway affecting hair colour. However, most of the associated loci overlap non-protein coding regions and many of the molecular mechanisms underlying pigmentation variation are still not understood. Here, we conduct GWAS meta-analyses of hair colour in a Canadian cohort of 12,741 individuals of European ancestry. By performing fine-mapping analyses we identify candidate causal variants in pigmentation loci associated with blonde, red and brown hair colour. Additionally, we observe colocalization of several GWAS hits with expression and methylation quantitative trait loci (QTLs) of cultured melanocytes. Finally, transcriptome-wide association studies (TWAS) further nominate the expression of EDNRB and CDK10 as significantly associated with hair colour. Our results provide insights on the mechanisms regulating pigmentation biology in humans.
Location-dependent threat and associated neural abnormalities in clinical anxiety
Authors: Suarez-Jimenez Benjamin , Balderston Nicholas L. , Bisby James A. , Leshin Joseph , Hsiung Abigail , King John A. , Pine Daniel S. , Burgess Neil , Grillon Christian , Ernst Monique 
Published: November 2021

AbstractAnxiety disorders are characterized by maladaptive defensive responses to distal or uncertain threats. Elucidating neural mechanisms of anxiety is essential to understand the development and maintenance of anxiety disorders. In fMRI, patients with pathological anxiety (ANX, n = 23) and healthy controls (HC, n = 28) completed a contextual threat learning paradigm in which they picked flowers in a virtual environment comprising a danger zone in which flowers were paired with shock and a safe zone (no shock). ANX compared with HC showed 1) decreased ventromedial prefrontal cortex and anterior hippocampus activation during the task, particularly in the safe zone, 2) increased insula and dorsomedial prefrontal cortex activation during the task, particularly in the danger zone, and 3) increased amygdala and midbrain/periaqueductal gray activation in the danger zone prior to potential shock delivery. Findings suggest that ANX engage brain areas differently to modulate context-appropriate emotional responses when learning to discriminate cues within an environment.
Using Peer Supports to Encourage Adolescents With Autism Spectrum Disorder to Show Interest in Their Conversation Partners
Authors: Bambara Linda M. , Cole Christine L. , Telesford Alana , Bauer Kathleen , Bilgili-Karabacak Irem , Weir Amanda , Thomas Amanda 
Published: November 2021

Purpose:
This study was conducted to evaluate the effects of a multicomponent peer-mediated intervention (PMI) on teaching adolescents with autism spectrum disorder (ASD) how to show interest in peer conversation partners by asking partner-focused questions about the person, their interests, or their experiences and by making partner-focused comments that positively affirm peer statements or express concern.

Method:

A multiple-baseline design across three verbally fluent high school students with ASD was used to assess the effects of the PMI, which involved training peers (
n
= 10) to support conversation and the students' use of target skills, and training the students to use partner-focused skills with the aid of a self-reflection cue sheet during conversation with trained peers in a high school cafeteria. Ten-minute samples of student–peer conversations were transcribed and analyzed. Generalization with untrained peers was assessed.

Results:
The PMI was highly effective in increasing all students' use of partner-focused skills. Gains were maintained by two students in a return-to-baseline condition. Generalization was evident for all students with varied results. Peers and students with ASD perceived the intervention to be beneficial.

Conclusions:
This study adds to the limited research showing that PMI can be used in high school settings to improve target conversational skills and provides preliminary evidence that PMI can successfully address an underresearched pragmatic language difficulty (i.e., introducing and maintaining topics of conversation of relevance and interest to conversation partners) common among adolescents with ASD. These findings invite replication to extend generality and assess the impact of the intervention on peer relationships.

Supplemental Material

https://doi.org/10.23641/asha.16915663
Audiovisual Speech Processing in Relationship to Phonological and Vocabulary Skills in First Graders
Authors: Gijbels Liesbeth , Yeatman Jason D. , Lalonde Kaylah , Lee Adrian K. C. 
Published: November 2021

Purpose:
It is generally accepted that adults use visual cues to improve speech intelligibility in noisy environments, but findings regarding visual speech benefit in children are mixed. We explored factors that contribute to audiovisual (AV) gain in young children's speech understanding. We examined whether there is an AV benefit to speech-in-noise recognition in children in first grade and if visual salience of phonemes influences their AV benefit. We explored if individual differences in AV speech enhancement could be explained by vocabulary knowledge, phonological awareness, or general psychophysical testing performance.

Method:
Thirty-seven first graders completed online psychophysical experiments. We used an online single-interval, four-alternative forced-choice picture-pointing task with age-appropriate consonant–vowel–consonant words to measure auditory-only, visual-only, and AV word recognition in noise at −2 and −8 dB SNR. We obtained standard measures of vocabulary and phonological awareness and included a general psychophysical test to examine correlations with AV benefits.

Results:
We observed a significant overall AV gain among children in first grade. This effect was mainly attributed to the benefit at −8 dB SNR, for visually distinct targets. Individual differences were not explained by any of the child variables. Boys showed lower auditory-only performances, leading to significantly larger AV gains.

Conclusions:
This study shows AV benefit, of distinctive visual cues, to word recognition in challenging noisy conditions in first graders. The cognitive and linguistic constraints of the task may have minimized the impact of individual differences of vocabulary and phonological awareness on AV benefit. The gender difference should be studied on a larger sample and age range.
Instance contrastive learning with dynamic weighted variance for small sample steel defect recognition
Authors: Liang Yanyang , Chen Jiacong , Zhou Wenlve , Xu Ying , Zhai Yikui , Labati Ruggero Donida , Piuri Vincenzo , Scotti Fabio 
Published: November 2021

AbstractAs an essential element in industrial steel, automatic defect recognition can guarantee the surface quality through focused supervised learning with ample labelled samples. However, defect recognition inevitably features with data‐limiting characteristic under the influence of costly expert labelling. To address this problem, a novel framework, Instance Contrast (InCo), is proposed with the inspiration of contrastive learning. This framework consists of two streams. One with instance labels attributed to the unlabelled data in each batch for classification, which is called Batch Instance Discrimination (BID). The other with different enhanced samples embedding of the same image aggregated by a new function named dynamic weighted variance loss (DWV loss). Therefore, better semantic features can be learned by model due to the moderation of embedding distance between similar steel defect images. Experimental results on the NEU‐CLS database validate that the proposed method achieves 89.86% classification accuracy with only fine‐tuning on the 1:32 training data, outperforming other general contrastive learning methods.
Design parameters of a reluctance actuation system for stable operation conditions with applications of high‐precision motions in lithography machines
Authors: Al Saaideh Mohammad , Alatawneh Natheer , Al Janaideh Mohammad 
Published: November 2021

AbstractRecently, the reluctance actuator has attracted great attention to replace the Lorentz actuator in the next generation of wafer scanners in semi‐conductor lithography machines. The reluctance actuator has a non‐linear position‐force characteristic, which may cause high oscillations and unstable operation. This study presents a linearisation technique by optimising the main parameters of the reluctance actuator to operate away from the saturation point. Also, in this study, the critical current is formulated for the stable dynamic behaviour of the reluctance actuator. Optimisation based on the Grey Wolf Optimiser is performed considering the high‐precision motion requirements and physical constraints. The high‐precision motion requirements include the desired work‐space displacement, natural frequency, and maximum force. The electromechanical dynamic model of the reluctance actuator motion system is formulated to characterise the interaction among electrical, magnetic, and mechanical parts. The simulation results show that the optimal design of the reluctance actuator works in the linear region, and for stable dynamic behaviour, the input current is limited by the critical current. Finally, a feedforward controller is designed based on the approximation of the force–current relationship to improve the tracking performances of the reluctance actuator motion system. The simulation results in time and frequency domains show an improvement in tracking performances using the feedforward controller.
Level of Diffusion and Training of Lung Ultrasound during the COVID-19 Pandemic – A National Online Italian Survey (ITALUS) from the Lung Ultrasound Working Group of the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI)
Authors: Vetrugno Luigi , Mojoli Francesco , Boero Enrico , Berchialla Paola , Bignami Elena Giovanna , Orso Daniele , Cortegiani Andrea , Forfori Francesco , Corradi Francesco , Cammarota Gianmaria , De Robertis Edoardo , Mongodi Silvia , Chiumello Davide , Poole Daniele , Ippolito Mariachiara , Biasucci Daniele Guerino , Persona Paolo , Bove Tiziana , Ball Lorenzo , Pelosi Paolo , Navalesi Paolo , Antonelli Massimo , Corcione Antonio , Giarratano Antonino , Petrini Flavia 
Published: November 2021

Abstract
Purpose The goal of this survey was to describe the use and diffusion of lung ultrasound (LUS), the level of training received before and during the COVID-19 pandemic, and the clinical impact LUS has had on COVID-19 cases in intensive care units (ICU) from February 2020 to May 2020.
Materials and Methods The Italian Lung Ultrasound Survey (ITALUS) was a nationwide online survey proposed to Italian anesthesiologists and intensive care physicians carried out after the first wave of the COVID-19 pandemic. It consisted of 27 questions, both quantitative and qualitative.
Results 807 responded to the survey. The median previous LUS experience was 3 years (IQR 1.0–6.0). 473 (60.9 %) reported having attended at least one training course on LUS before the COVID-19 pandemic. 519 (73.9 %) reported knowing how to use the LUS score. 404 (52 %) reported being able to use LUS without any supervision. 479 (68.2 %) said that LUS influenced their clinical decision-making, mostly with respect to patient monitoring. During the pandemic, the median of patients daily evaluated with LUS increased 3-fold (p < 0.001), daily use of general LUS increased from 10.4 % to 28.9 % (p < 0.001), and the daily use of LUS score in particular increased from 1.6 % to 9.0 % (p < 0.001).
Conclusion This survey showed that LUS was already extensively used during the first wave of the COVID-19 pandemic by anesthesiologists and intensive care physicians in Italy, and then its adoption increased further. Residency programs are already progressively implementing LUS teaching. However, 76.7 % of the sample did not undertake any LUS certification.