bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Changes in Puffing Intensity When Exclusively Using Open-Label Very Low Nicotine Content Cigarettes
Authors: White Cassidy M , Watson Clifford , Bravo Cardenas Roberto , Ngac Phuong , Valentin-Blasini Liza , Blount Benjamin C , Koopmeiners Joseph S , Denlinger-Apte Rachel L , Pacek Lauren R , Benowitz Neal L , Hatsukami Dorothy K , Donny Eric C , Carpenter Matthew J , Smith Tracy T 
Published: May 2022

Abstract

Introduction
In response to reducing cigarette nicotine content, people who smoke could attempt to compensate by using more cigarettes or by puffing on individual cigarettes with greater intensity. Such behaviors may be especially likely under conditions where normal nicotine content (NNC) cigarettes are not readily accessible. The current within-subject, residential study investigated whether puffing intensity increased with very low nicotine content (VLNC) cigarette use, relative to NNC cigarette use, when no other nicotine products were available.

Aims and Methods
Sixteen adults who smoke daily completed two four-night hotel stays in Charleston, South Carolina (United States) in 2018 during which only NNC or only VLNC cigarettes were accessible. We collected the filters from all smoked cigarettes and measured the deposited solanesol to estimate mouth-level nicotine delivery per cigarette. These estimates were averaged within and across participants, per each 24-h period. We then compared the ratio of participant-smoked VLNC and NNC cigarette mouth-level nicotine with the ratio yielded by cigarette smoking machines (when puffing intensity is constant).

Results
Average mouth-level nicotine estimates from cigarettes smoked during the hotel stays indicate participants puffed VLNC cigarettes with greater intensity than NNC cigarettes in each respective 24-h period. However, this effect diminished over time (p &lt; .001). Specifically, VLNC puffing intensity was 40.0% (95% CI: 29.9, 53.0) greater than NNC puffing intensity in the first period, and 16.1% (95% CI: 6.9, 26.0) greater in the fourth period.

Conclusion
Average puffing intensity per cigarette was elevated with exclusive VLNC cigarette use, but the extent of this effect declined across four days.

Implications
In an environment where no other sources of nicotine are available, people who smoke daily may initially attempt to compensate for cigarette nicotine reduction by puffing on individual cigarettes with greater intensity. Ultimately, the compensatory behavior changes required to achieve usual nicotine intake from VLNC cigarettes are drastic and unrealistic. Accordingly, people are unlikely to sustain attempts to compensate for very low cigarette nicotine content.
The HD-Zip transcription factor SlHB15A regulates abscission by modulating jasmonoyl-isoleucine biosynthesis
Authors: Liu Xianfeng , Cheng Lina , Li Ruizhen , Cai Yue , Wang Xiaoyang , Fu Xin , Dong Xiufen , Qi Mingfang , Jiang Cai-Zhong , Xu Tao , Li Tianlai 
Published: May 2022

Abstract
Plant organ abscission, a process that is important for development and reproductive success, is inhibited by the phytohormone auxin and promoted by another phytohormone, jasmonic acid (JA). However, the molecular mechanisms underlying the antagonistic effects of auxin and JA in organ abscission are unknown. We identified a tomato (Solanum lycopersicum) class III homeodomain-leucine zipper transcription factor, HOMEOBOX15A (SlHB15A), which was highly expressed in the flower pedicel abscission zone and induced by auxin. Knocking out SlHB15A using clustered regularly interspaced short palindromic repeats-associated protein 9 technology significantly accelerated abscission. In contrast, overexpression of microRNA166-resistant SlHB15A (mSlHB15A) delayed abscission. RNA sequencing and reverse transcription-quantitative PCR analyses showed that knocking out SlHB15A altered the expression of genes related to JA biosynthesis and signaling. Furthermore, functional analysis indicated that SlHB15A regulates abscission by depressing JA-isoleucine (JA-Ile) levels through inhabiting the expression of JASMONATE-RESISTANT1 (SlJAR1), a gene involved in JA-Ile biosynthesis, which could induce abscission-dependent and abscission-independent ethylene signaling. SlHB15A bound directly to the SlJAR1 promoter to silence SlJAR1, thus delaying abscission. We also found that flower removal enhanced JA-Ile content and that application of JA-Ile severely impaired the inhibitory effects of auxin on abscission. These results indicated that SlHB15A mediates the antagonistic effect of auxin and JA-Ile during tomato pedicel abscission, while auxin inhibits abscission through the SlHB15A–SlJAR1 module.
Hierarchical Symptom Components in Early Psychosis
Authors: Longenecker Julia M , Haas Gretchen L , Salisbury Dean F 
Published: May 2022

Abstract

Background and Hypothesis
Quantitative models of psychopathology can empirically guide subclassification of heterogeneous clinical presentations such as psychosis; they are particularly well-equipped to capture the nuanced symptomatology observed in first-episode psychosis. As well, components may be better aligned with biological variables. The current study sought to confirm and extend knowledge of the hierarchical structure of psychosis symptoms in first-episode psychosis. Based on past hierarchical work, we hypothesized that a 4 component level would be most closely associated with longitudinal disability.

Study Design
Participants with early-stage psychosis (N = 370) underwent clinical assessment with the scale for the assessment of positive symptoms (SAPS), scale for assessment of negative symptoms (SANS), and global assessment scale(GAS). A subset was assessed at 6 months (N = 221) and 1 year (N = 207). Hierarchical symptom components were extracted at 12 levels. The predictive utility of the components for global functioning was tested.

Study Results
As predicted, the 4-component model (reality distortion, thought disorder, inexpressivity, apathy/asociality) provided a superior prediction of functioning over other levels of the hierarchy. Baseline apathy/asociality longitudinally predicted functioning beyond the shared variance of the components at 6 months (b = −4.83, t(216) = −5.37, p &lt; .001, R2adj = 0.12) and 1-year (b = −4.49, t(202) = −4.38, p &lt; .001, R2adj = 0.09).

Conclusions
The hierarchical structure of psychotic symptomatology and its external validity have been robustly established in independent, longitudinal first-episode psychosis samples. The established model incorporates multiple levels of granularity that can be flexibly applied based on the level that offers the greatest predictive utility for external validators.
Porcine Pluripotent Stem Cells Established from LCDM Medium with Characteristics Differ from Human and Mouse Extended Pluripotent Stem Cells
Authors: Yu Zhuoran , Zhou Sihan , Liu Minli , Chen Lijun , Zhang Xue , Yang Xu , Cui Hongdi , Jiang Chaoqian , Lv Yanjiao , Yan Tingsheng , Kong Qingran , Liu Zhonghua 
Published: May 2022

Abstract
Pluripotent stem cells (PSCs) have unlimited self-renewal and multifunctional development potential in vitro. Porcine PSCs are highly desirable due to the conserved characteristics between pigs and humans. Extended PSCs (EPSCs) are additionally capable of differentiating into embryonic (Em) and extraembryonic (E×Em) parts. Here, we employed the LCDM culture system (consisting of human LIF, CHIR99021, (S)-(+)-dimethindene maleate, and minocycline hydrochloride), which can establish EPSCs from humans and mice, to derive and maintain stable porcine PSCs (pLCDM) from in vivo blastocysts. Transcriptome analysis revealed the unique molecular characteristics of pLCDMs compared with early-stage embryos. Meanwhile, the parallels and differences in the transcriptome features among pLCDMs, human EPSCs, and mouse EPSCs were carefully analyzed and evaluated. Most noteworthy, the trophoblast lineage differentiation tendency of pLCDMs was clarified by inducing trophoblast-like cells and trophoblast stem cells (TSCs) in vitro. Further research found that 2 of the small molecules in LCDM culture system, (S)-(+)-dimethindene maleate (DiM) and minocycline hydrochloride (MiH), probably play a crucial role in promoting trophoblast lineage differentiation potential of pLCDMs.
Effects of Low Level Laser Therapy on Tendinopathies: A Systematic Literature Review
Authors: Pham Hieu , Baloy Rodiel K. 
Published: May 2022

BackgroundActive individuals may become afflicted by degeneration of tendon protein collagen. This phenomenon, termed tendinopathy, manifests with pain, swelling, and loss of function. Low Level Laser Therapy (LLLT) is a proposed modality for the management of pain and inflammation associated with tendinopathies.PurposeThis literature review aims to look at the state of evidence among previously conducted randomized controlled trials (RCT) examining the effects of LLLT on tendinopathies in humans.Methods and Data ExtractionSystematic literature searches for randomized controlled trials between 2011‐2021 were performed in the databases of PubMed, PEDro, CINAHL, Cochrane, and Medline between July 7 to 23, 2021. A total of three randomized controlled trials (full text available, PEDro score > 6, met search criteria, and conducted in the past 10 years) with a total of 132 subjects met quality guidelines using the PEDro scale.ResultsA total of 171 articles were screened, and three studies with a total population of n=132 were included. With heterogeneity in frequency, dosage, and volume of treatment prescription, no meta‐analysis was conducted. Majority of the RCT’s did not meet PEDro quality guidelines (6 of 10 total points). Of the three studies that met criteria, there were statistically significant improvements reported in terms of pain and function in 2 of the 3 studies (n=92). On the other hand, no notable clinically significant effects were found in 1 of the studies (n=40). The results suggest that in the management of tendinopathies, the use of LLLT has some clinically significant effect on pain and functional outcomes.Conclusion and RecommendationsThis review of current randomized controlled trials and systematic reviews presented limited evidence for LLLT for tendinopathies. While the use of LLLT may improve pain and functional outcome, improving the quality of RCT’s, their methodology, and dosing and prescription guidelines are suggested.
iTRAQ proteomics of sentinel lymph nodes for the identification of extra cellular matrix protein signatures that can flag metastasis in early breast cancer
Authors: Hariprasad Gururao , Pathania Sheetal , Bandyopadhyay Sabyasachi , Mishra Piyush R. , Mathur Sandeep , Hari Smriti 
Published: May 2022

BackgroundBreast cancer patients who present in the early stage of disease are affected by metastasis to the axillary group of lymph nodes. The first among this group that is affected is called as sentinel lymph node, and metastasis to this lymph node is crucial for the staging of cancer and the quality of surgical intervention. Sentinel Lymph Node Biopsy (SLNB) that is currently used to assess lymph node metastasis is neither sensitive, nor specific, is time‐consuming, thereby necessitating the identification of novel biomarkers that can flag sentinel lymph node metastasis.MethodsThis study was conducted after approval was obtained from the Institute Ethics Committee (Ref. No. IECPG‐ 27/23.01.2019, RT‐03/28.02.2019). Breast cancer patients were screened, and those with early stage were recruited in the study. Surgical resection of the breast was followed by identification of sentinel lymph nodes by methylene fluorescent technique. Histo‐pathology of fresh frozen section biopsy was used as the gold standard to assign the clinical phenotypes of metastatic (SLNM+) and non‐metastatic sentinel lymph nodes (SLNM‐). Discovery phase of the experiment included isobaric Tags for Relative and Absolute Quantitation (iTRAQ) technique comprising of six comparative experiments coupled with mass spectrometric analysis to identify differentially expressed proteins. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD027668. Validation was done by ELISA and protein concentrations were used to estimate the ROC for computing diagnostic parameters. Pathway analysis and gene ontology analysis was done to understand the relevance of the differentially expressed proteins in this study.ResultsBased on MS/MS spectra there were 7510 differentially expressed proteins comparing SLNB + and SLNB ‐. Nineteen proteins up‐regulated, and eight proteins that were down regulated in SLNB+ as compared to SLNB‐. ELISA confirmed the up‐regulation of caveolin 1, collagen α‐1, desmin, fibrillin‐1, and microfibrillar associated glycoprotein 4 in metastatic, as compared to non‐metastatic lymph nodes. These proteins are known to be integral in tumorogenesis, cell proliferation, invasion, cell survival and anti‐apoptosis. These proteins have 80%‐100%, of sensitivity and specificity to differentiate the two clinical phenotypes.ConclusionIdentified protein biomarkers have requisite diagnostic parameters to be developed as a translational tool to assess the status of sentinel lymph nodes during mastectomy procedure to guide surgical therapy of axillary lymph nodes in early breast oncology.
Structure and function of DNA transposition assemblies involved in antibiotic resistance spreading
Authors: Barabas Orsolya , Smyshlyaev Georgy , Isbilir Buse , Khedkar Supriya , Rojas‐Cordova Carlos , Bateman Alex G. , Bork Peer 
Published: May 2022

Transposons are mobile genetic elements that drive evolution and adaptation throughout the tree of life. In bacteria, they often transfer antibiotic resistance genes and contribute to the emergence of multidrug‐resistant pathogens.In this talk, I will present our recent discoveries on a group of transposons that efficiently propagate antibiotic resistance genes across diverse microbial communities. Using a dedicated computational pipeline, we mapped the most wide‐spread transposons in bacterial genomes and characterized their diversity, genetic cargo, and transfer dynamics. Selected elements were experimentally reconstituted to describe their molecular mechanisms and biochemical pathways. We determined numerous high‐resolution crystal and cryo‐EM structures of the protein‐DNA assemblies involved in transposon movement. The structures capture various stages of transposition and reveal an intricate interplay between the core transposition machinery and host‐encoded proteins. Protein interactions shape transposon and genomic DNA in unique ways to cut, exchange and re‐join strands in a tightly regulated manner. Importantly, our data also explain how specific DNA distortion and cleavage mechanisms enable the transposons to move between diverse genomic sites, expanding gene transfer across many species.These results shed new light onto the molecular strategies of antibiotic resistance carrying transposons and show how they evolved to effectively spread key genetic traits. Our insights also open new opportunities to develop strategies for blocking transposition and thereby help control resistance spreading.
SLC3A2 N‐glycosylation and alternate evolutionary trajectories for amino acid metabolism
Authors: Dennis James W. , Zhang Cunjie , Pawling Judy , Hesketh Geoff G. , Dransart Eselle , Shafaq‐Zahah Massiullah , Penn Linda Z. , Gingras Anne‐Claude , Johannes Ludger 
Published: May 2022

Cancer and other proliferative diseases are driven by cooperative rewiring of growth signaling and metabolism, where posttranslational modifications to proteins play a critical role in maintaining the disease state. Most PTMs require metabolites as donor substrates, providing underappreciated link between metabolism and signaling. Protein N‐glycosylation and Golgi remodeling of N‐glycan on receptor kinases, T cell receptor, glucagon receptor, and glucose transporters provides feedback between signaling and metabolism. In turn, N‐glycosylation requires uridine diphosphate N‐acetylglucosamine (UDP‐GlcNAc), generated by the hexosamine biosynthesis pathway (HBP) from glucose, glutamine and acetyl‐CoA, where the flux of these substrates into UDP‐GlcNAc are in competition with glycolysis, glutaminolysis and fatty‐acid turnover. Thus, N‐glycan branching, a pathway of N‐acetylglucosaminyltransferases (MGAT1, 2, 4 and 5, avian 6) in the Golgi, is a sensor of central metabolism.In a search for additional glycoproteins that link metabolism, N‐glycosylation and signaling, we identified SLC3A2 (4F2hc, CD98),an adaptor to amino acid (AA) transporters SLC7A5‐11, ‐13 which stabilizes cell surface residency. The SLC3A2*SLC7A5 exchanger imports essential AA that stimulate mTOR signaling and anabolic metabolism, while SLC3A2*SLC7A11 supports glutathione synthesis and mitigation of oxidative stress. Analysis of SLC3A2 N‐glycans revealed stable site‐specific profiles of Golgi remodeling, with the exception of the conserved N365 where branching and poly‐N‐acetyllactosamine content were sensitive to the insertion of lost ancestral sites and to HBP. The N‐glycans are positioned to promote galectin‐mediated clustering with N‐glycosylated Na++/AA symporters and enhance diffusion‐limited flux between exchangers and AA /Na+ symporters. In a successful experiment of Nature, SLC3A2 has been deleted in Neoaves, a clade representing 95% of Ave species that are adapted for flapping flight, the most metabolically intense form of vertebrate locomotion. Neoaves have also acquired a unique N‐glycan branching specificity GnT‐VI (Mgat6, Q9DGD1), which may support an alternate clustering of N‐glycosylated transporters. KEAP1, and four SLC7A family exchangers are also absent, and two others have duplicated, consistent with a shift in metabolic imperatives of Neoaves. The fate of these genes in Primates, Neoaves and Naked mole rat highlights the tension between metabolic rates and oxidative stress that govern lifestyle and longevity.
Creative strategies to perform an inclusive faculty search
Authors: Corbett Anita H. 
Published: May 2022

During the academic year 2020‐2021, the Biology Department at Emory University conducted a faculty search that was designed to continue the success of the department in building an inclusive department. There were several actions taken to ensure an equitable search process despite the challenges and biases inherent in search processes that were likely further exacerbated by a raging global pandemic.The search was approved for two tenure track faculty positions with no formal limitation on the academic rank of the hires. The whole department invested in efforts to have a very broad search that would have the highest likelihood of identifying and recruiting outstanding scientists with a commitment to teaching who also showed evidence of actions toward the mission of diversity, equity, and inclusion.For this search, we modified aspects of our traditional search in several ways that included the strategy for the search, the ad that described the position, the composition of the search committee, which was expanded to include trainee members, and aspects of the process (performed largely virtually due to COVID‐19). We were fortunate to have strong support from leadership at all levels from the Department to the Dean and Dean’s Office to allow us to make changes aligned with the goals of the search.A successful search takes a great deal of time and effort dedicated from the search committee as well as all members of the department. The input from trainees, which was new to our process, was invaluable. We will seek to incorporate some of the lessons learned during this recent experience in future searches, with the caveat that we all hope to hold future searches in person. However, there are aspects of the virtual process that may enhance equity and, thus, should be considered for the future. Each search is unique with distinct challenges and opportunities, but there are concrete actions we can take to mitigate bias in the process.
Chronic stress, omics, and asthma
Authors: Celedon Juan C. 
Published: May 2022

The U.S. has the highest rate of firearm‐related deaths of all economically developed nations. Current evidence suggests that exposure to violence (ETV) and violence‐related distress may cause or worsen asthma. Indeed, violence‐related distress may affect asthma pathogenesis through direct effects including abnormal responses to catecholamines and glucocorticoid therapy, and altered immune responses resulting in airway inflammation. Violence‐related distress may also affect asthma through indirect effects such as decreased physical activity and weight gain.We previously showed that ETV is associated with asthma in a high‐risk population (Puerto Ricans), in whom ETV is also associated with methylation of a CpG site in the promoter of the gene for the pituitary adenylate cyclase activating polypeptide 1 type 1 receptor (ADCYAP1R1) in white blood cells. Moreover, we reported that such methylation is associated with childhood asthma in Puerto Ricans.Based on previous results, we hypothesized that ETV and violence‐related distress would be linked to asthma through airway epithelial methylation of genes regulating autonomic, neuroendocrine, and immune responses. To examine this hypothesis, we carried out a epigenome‐wide association study (EWAS) of ETV or chronic stress measures and nasal (airway) epithelial methylation in 487 Puerto Rican participants (aged 9 to 20 years) in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA‐PR]). We evaluated four measures of ETV and chronic stress in children (ETV scale, gun violence, and perceived stress) and their mothers (perceived stress). Linear regression was used for each of the EWASs, with CpGs as dependent variables and the violence or stress scale as a predictor, adjusting for age, sex, principal components, and latent factors. We then selected the top 100 CpGs (by P‐value) associated with each scale in EVA‐PR. Since no replication cohort had data on stress or violence, we conducted a meta‐analysis of the selected CpGs and atopic asthma using data from EVA‐PR and two other cohorts (Project Viva and PIAMA).Three CpGs (in SNN, PTPRN2,and LINC01164) were associated with maternal stress or gun violence (P=1.28 to 3.36 ×10‐7), but not with atopic asthma, in EVA‐PR. In a meta‐analysis of three cohorts, which included the top CpGs associated with stress/violence measures in EVA‐PR, 12 CpGs (in STARD3NL, SLC35F4, TSR3, CDC42SE2, KLHL25, PLCB1, BUD13, OR2B3, GALR1, TMEM196, TEAD4 and ANAPC13) were associated with atopic asthma at FDR‐P< 0.05. PLCB1 has been associated with bronchodilator response and is differentially expressed in children with treatment‐resistant asthma compared with children with controlled persistent asthma or healthy controls.Pending confirmation in longitudinal studies, our results suggest that nasal epithelial methylation markers associated with ETV and chronic stress may be linked to atopic asthma in youth.