bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aesthetic Specialization: A Comparative Study Across Medical and Surgical Specialties
Authors: Katz Abigail , Oleru Olachi , Wang Anya , Seyidova Nargiz , Mandelbaum Max , Melamed Eitan , Taub Peter J. 
Published: October 2024

Background:
Post-residency fellowship training has become increasingly popular as a career option. Specifically, the subspecialty of aesthetic surgery has grown tremendously over the past two decades within several fields, including plastic and reconstructive surgery (PRS), otolaryngology, dermatology, and ophthalmology. However, the popularity of aesthetic specialization through fellowship remains unknown. The present study aims to analyze trends in aesthetic specialization across these specialties and compare its popularity to other fellowships.

Methods:
A retrospective review of data from the San Francisco Match, National Resident Matching Program, American Society for Dermatologic Surgery, and the Accreditation Council for Graduate Medical Education was performed. Data on graduating residents and applicants to fellowship were collected. ANOVA and t-tests were used to compare differences between groups.

Results:
Significant disparities were observed in applicants and matched applicants to aesthetic fellowships among the four residencies (p<0.001). Aesthetic fellowship was the most popular option after otolaryngology residency (12.5%-27% depending on the year) and second most popular choice after PRS (8%-17%) and dermatology (2%-5%). A comparison between PRS and otolaryngology demonstrated a significantly higher percent of the latter choosing aesthetic fellowship over time (p<0.001). However, no significant difference in applicants to aesthetic fellowship was found between dermatology and ophthalmology (t-test, p=0.060).

Conclusions:
The number of applicants to aesthetic fellowship has increased over time across all eligible residencies with the more surgical heavy specialties (ENT and PRS) having the highest percent of applicants. Differences in aesthetic training between fields was also observed, which may reflect underlying variations in training and residency exposure.
Overlooked and misunderstood: can glutathione conjugates be clues to understanding plant glutathione transferases?
Authors: Micic Nikola , Holmelund Rønager Asta , Sørensen Mette , Bjarnholt Nanna 
Published: September 2024

Plant glutathione transferases (GSTs) constitute a large and diverse family of enzymes that are involved in plant stress response, metabolism and defence, yet their physiological functions remain largely elusive. Consistent with the traditional view on GSTs across organisms as detoxification enzymes,in vitromost plant GSTs catalyse glutathionylation, conjugation of the tripeptide glutathione (GSH; γ-Glu-Cys-Gly) onto reactive molecules. However, when it comes to elucidating GST functions, it remains a key challenge that the endogenous plant glutathione conjugates (GS-conjugates) that would result from such glutathionylation reactions are rarely reported. Furthermore, GSTs often display high substrate promiscuity, and their proposed substrates are prone to spontaneous chemical reactions with GSH; hence, single-gene knockouts rarely provide clear chemotypes or phenotypes. In a few cases, GS-conjugates are demonstrated to be biosynthetic intermediates that are rapidly further metabolized towards a pathway end product, explaining their low abundance and rare detection. In this review, we summarize the current knowledge of plant GST functions and how and possibly why evolution has resulted in a broad and extensive expansion of the plant GST family. Finally, we demonstrate that endogenous GS-conjugates are more prevalent in plants than assumed and suggest they are overlooked as clues towards the identification of plant GST functions.This article is part of the theme issue ‘The evolution of plant metabolism’.
The transcriptomic response of cells of the thermophilic bacteriumGeobacillus icigianusto terahertz irradiation
Authors: Peltek Sergey , Bannikova Svetlana , Khlebodarova Tamara , Uvarova Yulia , Mukhin Aleksey , Vasiliev Gennady , Scheglov Mikhail , Shipova Aleksandra , Vasilievа Asya , Oshchepkov Dmitry , Bryanskaya Alla , Popik Vasiliy 
Published: September 2024

ABSTRACTAs areas of application of terahertz (THz) radiation expand in science and practice, evidence is accumulating that this type of radiation can affect not only biological molecules directly but also cellular processes as a whole. In this study, the transcriptome in cells of the thermophilic bacteriumGeobacillus icigianuswas analyzed immediately after THz irradiation (0.23 W/cm2, 130 μm, 15 min) and at 10 min after its completion. THz irradiation does not affect the activity of heat shock protein genes and diminishes the activity of genes whose products involved in peptidoglycan recycling, participate in redox reactions and in protection of DNA and proteins from damage, including genes of chaperone protein ClpB and of DNA repair protein RadA as well as genes of catalase and kinase McsB, which play an essential role in the regulation of the cellular response to oxidative stress. Gene systems responsible for the homeostasis of transition metals (copper, iron, and zinc) proved to be the most sensitive to THz irradiation; downregulation of these systems increased significantly 10 min after the end of the irradiation. Blockage of the expression of genes responsible for copper export and iron import systems under the influence of THz irradiation may be a harbinger of toxic stress inG. icigianuscells, which leads to destabilization of the function of proteins containing Fe/S clusters. It was also hypothesized that some negative effects of THz radiation on metabolism inG. icigianuscells are related to disturbances in activities of gene systems controlled by metal-sensitive transcription factors.
Distinct regulatory mechanisms by the nuclear Argonautes HRDE-1 and NRDE-3 in the soma ofCaenorhabditis elegans
Authors: Mendoza Hector , Jash Eshna , Davis Michael B. , Haines Rebecca A. , Van Diepenbos Sarah , Csankovszki Györgyi 
Published: September 2024

ABSTRACTRNA interference is a conserved silencing mechanism that depends on the generation of small RNA molecules that disrupt synthesis of their corresponding transcripts. Nuclear RNA interference is a unique process that triggers regulation through epigenetic alterations to the genome. This pathway has been extensively characterized inCaenorhabditis elegansand involves the nuclear recruitment of H3K9 histone methyltransferases by the Argonautes HRDE-1 and NRDE-3. The coordinate regulation of genetic targets by H3K9 methylation and the nuclear Argonautes is highly complex and has been mainly described based on the small RNA populations that are involved.Recent studies have also linked the nuclear RNAi pathway to the compaction of the hermaphrodite X chromosomes during dosage compensation, a mechanism that balances genetic differences between the biological sexes by repressing X chromosomes in hermaphrodites. This chromosome-wide process provides an excellent opportunity to further investigate the relationship between H3K9 methylation and the nuclear Argonautes from the perspective of the transcriptome. Our work suggests that the nuclear RNAi and the H3K9 methylation pathways each contribute to the condensation of the X chromosomes during dosage compensation but the consequences on their transcriptional output are minimal. Instead, nuclear RNAi mutants exhibit global transcriptional differences, in which HRDE-1 and NRDE-3 affect expression of their native targets through different modes of regulation and different relationships to H3K9 methylation.ARTICLE SUMMARYThis study examines the transcriptional consequences during the disruption of the nuclear RNAi silencing mechanism inC. elegans. Through microscopy and bioinformatic work, we demonstrate that although nuclear RNAi mutants exhibit significantly decondensed X chromosomes, chromosome-wide transcriptional de-repression is not detectable. Downstream analyses further explore the global influence of the nuclear RNAi pathway, indicating that the nuclear Argonautes HRDE-1 and NRDE-3 function through two distinct mechanisms.
PP mediated the relationship between METS-IR and AIS in non-diabetic patients
Authors: Li Zhaoyang , Jia Ruirui , Chen Dong , Wang Hui , Zhang Youyou 
Published: September 2024

AbstractBackgroundThe correlation between metabolic score for insulin resistance (METS-IR) and high insulin normal glucose clamp test is stronger than other non-insulin-based insulin resistance scores. Insulin resistance was related to the occurrence and development of hypertension and stroke, however, the association between METS-IR and hypertension, as well as ischemic stroke is lack of evidence. This study aimed to determine the association between METS-IR and acute ischemic stroke in non-diabetic patients, and the mediating role of blood pressure parameters on it.MethodsThis hospital-based study included 557 non-diabetic subjects diagnosed with premature acute ischemic stroke. Logistic regression models and mediation analyses were conducted to assess the role of blood pressure parameters (systolic blood pressure, diastolic blood pressure, pulse pressure and mean arterial pressure) in the associations between METS-IR and risk of acute ischemic stroke.ResultsAfter adjusting for potential covariates, each SD increment of METS-IR was associated with 26% higher odds (OR = 1.26, 95% CI: 1.06-1.52) increment in ORs of acute ischemic stroke. The OR for acute ischemic stroke in patients with highest quartile of METS-IR was 1.73 hold (OR = 1.73, 95% CI: 1.12-2.70) higher than that in those with the lowest quartile of METS-IR. Furthermore, mediation analyses indicated that pulse pressure partially mediate the detrimental effect of insulin resistance (assessed by the METS-IR) on acute ischemic stroke (mediation percentage: 11.70%).ConclusionsOur study suggests a relationship between METS-IR and acute ischemic stroke, and the association of METS-IR with acute ischemic stroke was partially mediated by pulse pressure.
Rapid prediction of thermodynamically destabilizing tyrosine phosphorylations in cancers
Authors: Woodard Jaie , Liu Zhengqing , Chegini Atena Malemir , Tian Jian , Bhowmick Rupa , Pennathur Subramanium , Mashaghi Alireza , Brender Jeffrey , Chandrasekaran Sriram 
Published: September 2024

AbstractTyrosine phosphorylations are a prominent characteristic of numerous cancers, necessitating the use of computational tools to comprehensively analyze phosphoproteomes and identify potentially (dys)functional phosphorylations. Here we propose a machine learning-based method to predict the thermodynamic stability change resulting from tyrosine phosphorylation. Our approach, based on prediction of phosphomimetic delta-delta-G from structural features, strongly correlates with experimental mutational scanning cDNA proteolysis data (R = 0.71). We predicted the destabilizing effects of all 384,857 tyrosine residues from the Alphafold2 database. We then applied our approach to a pan-cancer phosphoproteomics dataset, comprising over 600 unique tyrosine phosphorylations across 11 cancer subtypes. We predict destabilizing phosphorylations in both oncogenes and tumor suppressors, where the former likely reflects a generalized relief of auto-inhibition or activating conformational change. We find that the number of circuit topological parallel relations with respect to residues contacting the phosphorylated site is greater for autoinhibited oncogenes than for other proteins (Wilcoxon p = 0.03). Utilizing an extreme gradient-boosting machine learning approach, we obtain an AUC of 0.85 for the prediction of autoinhibited phosphorylation states from circuit topological features. The top destabilized proteins from the pan-cancer data are enriched for chemical and oxidative stress pathways. Among metabolic proteins, highly destabilizing phosphorylations tend to occur in more peripheral proteins with lower network centrality measures (Wilcoxon p = 0.005). We predict 58% of recurrent tyrosine cancer phosphorylations to be destabilizing at the 1 kcal/mol threshold. Our approach can enable rapid screening of destabilizing phosphorylations and phosphomimetic mutations.
mTORC1 and STAT3 signalings are indispensable for in vitro TGFβ1-dependent Three-Dimensional (3D) tendon construct
Authors: Koo Bon-hyeock , Smith Aiden , Joeng Kyu Sang 
Published: September 2024

ABSTRACTThe Transforming Growth Factor-β 1 (TGFβ1) is a well-known growth factor involved in tenocytes differentiation, extracellular matrix production, and cell fate regulation. We previously demonstrated that TGFβ1 has a critical role in the formation ofin vitro3D tendon constructs using mouse primary tendon cells. In this study, we investigated the function of Mammalian target of rapamycin complex 1 (mTORC1) and Signal transducer and activator of transcription 3 (STAT3) signaling in the formation of TGFβ1-inducedin vitro3D tendon constructs using specific inhibitors, rapamycin (mTORC1 inhibitor) and stattic (stat3 inhibitor). TGFβ1 treatment activated both mTORC1 and STAT3 in 3D tendon constructs. The treatment of rapamycin or stattic partly attenuated TGFβ1-dependent cellular, molecular, and matrix changes in the 3D tendon constructs. Overall, this study demonstrates that mTORC1-STAT3 signaling axis is a downstream mediator of TGFβ1 signaling in the formation of 3D tendon constructs.
Potentiation of active locomotor state by spinal-projecting serotonergic neurons
Authors: Fenstermacher Sara J. , Vonasek Ann , Gattuso Hannah , Chaimowitz Corryn , Dymecki Susan M. , Jessell Thomas M. , Dasen Jeremy S. 
Published: September 2024

AbstractAnimals produce diverse motor actions that enable expression of context-appropriate behaviors. Neuromodulators facilitate behavioral flexibility by altering the temporal dynamics and output of neural circuits. Discrete populations of serotonergic (5-HT) neurons target circuits in the brainstem and spinal cord, but their role in the control of motor behavior is unclear. Here we define the pre- and post-synaptic organization of the spinal-projecting serotonergic system and define a role in locomotor control. We show that while forebrain-targeting 5-HT neurons decrease their activity during locomotion, subpopulations of spinal projecting neurons increase their activity in a context-dependent manner. Optogenetic activation of ventrally projecting 5-HT neurons does not trigger initiation of movement, but rather enhances the speed and duration of ongoing locomotion over extended time scales. These findings indicate that the descending serotonergic system potentiates locomotor output and demonstrate a role for serotonergic neurons in modulating the temporal dynamics of motor circuits.
Untargeted CUT&Tag and BG4 CUT&Tag are both enriched at G-quadruplexes and accessible chromatin
Authors: Thompson Matthew , Byrd Alicia 
Published: September 2024

ABSTRACTG-quadruplex DNA structures (G4s) form within single-stranded DNA in nucleosome-free chromatin. As G4s modulate gene expression and genomic stability, genome-wide mapping of G4s has generated strong research interest. Recently, the Cleavage Under Targets and Tagmentation (CUT&Tag) method was performed with the G4-specific BG4 antibody to target Tn5 transposase to G4s. While this method generated a novel high-resolution map of G4s, we unexpectedly observed a strong correlation between the genome-wide signal distribution of BG4 CUT&Tag and accessible chromatin. To examine whether untargeted Tn5 cutting at accessible chromatin contributes to BG4 CUT&Tag signal, we examined the genome-wide distribution of signal from untargeted (i.e. negative control) CUT&Tag datasets. We observed that untargeted CUT&Tag signal distribution was highly similar to both that of accessible chromatin and of BG4 CUT&Tag. We also observed that BG4 CUT&Tag signal increased at mapped G4s, but this increase was accompanied by a concomitant increase in untargeted CUT&Tag at the same loci. Consequently, enrichment of BG4 CUT&Tag over untargeted CUT&Tag was not increased at mapped G4s. These results imply that either the vast majority of accessible chromatin regions contain mappable G4s or that the presence of G4s within accessible chromatin cannot reliably be determined using BG4 CUT&Tag alone.GRAPHICAL ABSTRACT
DNA polymerase ζ is a robust reverse transcriptase
Authors: Mayle Ryan , Holloman William K. , O’Donnell Michael E. 
Published: September 2024

AbstractCell biology and genetic studies have demonstrated that DNA double strand break (DSB) repair can be performed using an RNA transcript that spans the site of the DNA break as a template for repair. This type of DSB repair requires a reverse transcriptase to convert an RNA sequence into DNA to facilitate repair of the break, rather than copying from a DNA template as in canonical DSB repair. Translesion synthesis (TLS) DNA polymerases (Pol) are often more promiscuous than DNA Pols, raising the notion that reverse transcription could be performed by a TLS Pol. Indeed, several studies have demonstrated that human Pol η has reverse transcriptase activity, while others have suggested that the yeast TLS Pol ζ is involved. Here, we purify all seven known nuclear DNA Pols ofSaccharomyces cerevisiaeand compare their reverse transcriptase activities. The comparison shows that Pol ζ far surpasses Pol η and all other DNA Pols in reverse transcriptase activity. We find that Pol ζ reverse transcriptase activity is not affected by RPA or RFC/PCNA and acts distributively to make DNA complementary to an RNA template strand. Consistent with priorS. cerevisiaestudies performedin vivo, we propose that Pol ζ is the major DNA Pol that functions in the RNA templated DSB repair pathway.
A Genetically Encoded Fluorescent Biosensor for Intracellular Measurement of Malonyl-CoA
Authors: Ranzau Brodie L. , Robinson Tiffany D. , Scully Jack M. , Kapelczack Edmund D. , Dean Teagan S. , TeSlaa Tara , Schmitt Danielle L. 
Published: September 2024

AbstractMalonyl-CoA is the essential building block of fatty acids and regulates cell function through protein malonylation and allosteric regulation of signaling networks. Accordingly, the production and use of malonyl-CoA is finely tuned by the cellular energy status. Most studies of malonyl-CoA dynamics rely on bulk approaches that take only a snapshot of the average metabolic state of a population of cells, missing out on dynamic changes in malonyl-CoA and fatty acid biosynthesis that could be occurring within a single cell. To overcome this limitation, we have developed a genetically encoded fluorescent protein-based biosensor for malonyl-CoA that can be used to capture malonyl-CoA dynamics in single cells. This biosensor, termed Malibu (malonyl-CoAintracellular biosensor to understand dynamics), exhibits an excitation-ratiometric change in response to malonyl-CoA binding. We first used Malibu to monitor malonyl-CoA dynamics during inhibition of fatty acid biosynthesis using cerulenin inE. coli, observing an increase in Malibu response in a time- and dose-dependent manner. In HeLa cells, we used Malibu to monitor the impact of fatty acid biosynthesis inhibition on malonyl-CoA dynamics in single cells, finding that two inhibitors of fatty acid biosynthesis, cerulenin and orlistat, which inhibit different steps of fatty acid biosynthesis, increase malonyl-CoA levels. Altogether, we have developed a new genetically encoded biosensor for malonyl-CoA, which can be used to sensitively study malonyl-CoA dynamics in single cells, providing an unparalleled view into fatty acid biosynthesis.
The extraordinarily long lead times of screen-detected lung cancer in never-smokers
Authors: Gao Wayne , Welch H Gilbert 
Published: September 2024

ABSTRACTBackgroundThe randomized trials of low-dose computed tomography (LDCT) screening enrolled individuals at high risk of lung cancer: heavy cigarette smokers. Nevertheless, opportunistic screening of never smokers has become commonplace in certain regions of East Asia. Lung cancer detection rates reported for this low risk group regularly exceed those reported in the randomized trials. We sought to determine the lead time – the length of time between screen detection and when symptoms would manifest (clinical presentation) – associated with LDCT detection rates reported in Taiwan.ObjectiveTo estimate the lead time for LDCT lung cancer detection in never smoking Taiwanese females, under the assumption that all detected cancers progress.MethodsWe analyzed data from the Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT), a prospective cohort of ≈12000 never smokers aged 55–75, and compared age-specific screen detection rates to lung cancer incidence rates in the pre-screening period. Lead time was estimated using Morrison’s approximation: one-half the ratio of screen detection to pre-screening incidence.ResultsInvasive lung cancer detection rates in never smoking females were 18 (age 70-74) to 37 (age 55-59) times higher than the respective age-specific lung cancer incidence rates prior to widespread screening. The estimated lead times for invasive lung cancers thus ranged from 9 (age 70-74) to 18.5 years (age 55-59). Had we included in situ lung cancer detection, the estimated lead time of screening would range from approximately 10 to 20 years.ConclusionIf all detected cancers progress, the lead times for LDCT lung cancer detection in never-smokers would be 5 to 20 times longer than that reported in the randomized trials of heavy smokers (1 to 2 years). Such extended lead times are not only undesirable (Why label and treat a patient for a cancer not destined to clinically present in the next 1 or 2 decades?), but also a major source of overdiagnosis – providing plenty of time for a patient to die from other causes before developing a symptomatic cancer (Type 1 overdiagnosis). Furthermore, some screen-detected cancers may not progress and thus have an infinite lead time (Type 2 overdiagnosis). Regardless, it appears that substantial overdiagnosis has occurred in screening low-risk, never smoking individuals.
Common pathogenic mechanisms for COVID-19 and differentiated thyroid cancer: a proteomic analysis
Authors: Liu Hanqing , Wang Jiaxi , Yang Dan , Chen Chuang 
Published: September 2024

AbstractBackgroundPrevious studies have proved that viral infection might have potential associations with differentiated thyroid cancer. COVID-19 has spread to hundreds of millions of individuals since Dec 2019. This study aimed to investigate the common pathogenic mechanisms of differentiated thyroid cancer and SARS-CoV-2 infection in thyroid tissues.MethodsThe proteomic profiles of COVID-19 and differentiated thyroid cancer were downloaded from iProx database and were analyzed for differentially expressed proteins. After the common proteins were identified using the Venn diagram, gene ontology and pathway enrichment analysis were performed. Subsequently, a protein-protein interaction network was constructed and hub genes were identified with eight algorithms. The diagnostic performance of hub genes was tested with the receiver operator characteristics curve. The associations between hub genes and diseases were evaluated with the Comparative Toxicogenomics Database.ResultsForty-nine common differentially expressed proteins were identified. Functional analysis revealed that the metabolism and transport of lipid and cholesterol and coagulation process were the main common biological activities affected by the two diseases. In addition, twelve genes, including AGT, AHSG, APOA2, APOM, C3, GC, ITIH2, KNG1, SERPINA1, SERPINC1, TF and TTR, were identified as the hub genes. These genes could serve as diagnostic markers for COVID-19 and differentiated thyroid cancers.ConclusionThe current study revealed common pathogenic mechanisms of COVID-19 and differentiated thyroid cancer. The concomitant infection of SARS-CoV-2 might exert adverse effects on patients with thyroid cancers.