bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multitranscriptome analyses of keloid fibroblasts reveal the role of the HIF-1α/HOXC6/ERK axis in keloid development
Authors: Wang Qi , Zhong Yixiu , Li Zhijia , Zhu Dingheng , Lu Hongyan , Chen Pingjiao , Li Changxing , Peng Xuebiao , Li Qian , Zeng Kang 
Published: April 2022

Abstract

Background
A keloid is a disease of excessive fibrosis that is characterized by the aberrant proliferation of fibroblasts. However, the molecular mechanisms of fibroblasts during the development of keloids remain unclear. This study aims to identify new molecular targets that promote the proliferation and migration of keloid fibroblasts, providing new ideas for the prevention and treatment of keloids.

Methods
We utilized bioinformatics tools to analyze data from keloid fibroblasts (KFs) available in the Gene Expression Omnibus (GEO) database to identify the key genes involved in keloid development. Homeobox C6 (HOXC6) emerged as a hub gene in KFs from the GEO database was verified in keloid tissue samples and KFs using reverse transcription-quantitative polymerase chain reaction, western blot (WB) and immunohistochemistry. Subsequently, the effects of downregulated HOXC6 expression on the cellular behaviors of KFs were examined by performing Cell Counting Kit-8, flow cytometry, transwell migration and WB assays. Meanwhile, we performed transcriptome sequencing and gene set enrichment analysis (GSEA) to further explore HOXC6-related mechanisms and validated the signaling pathways by performing a series of experiments.

Results
HOXC6 was the top-ranking hub gene of KFs in microarray datasets from GEO and was upregulated in keloid tissue samples and KFs. Downregulation of HOXC6 inhibited proliferation, migration and extracellular matrix (ECM) accumulation and promoted KF apoptosis. GSEA predicted that the hypoxia signaling pathway was associated with HOXC6 in KFs. Transcriptome sequencing suggested that the extracellular regulated protein kinase (ERK) pathway was one of the downstream pathways of HOXC6 in KFs. Our experiments confirmed that hypoxia-inducible factor-1α (HIF-1α) upregulates HOXC6, contributing to KFs proliferation, migration, apoptosis inhibition and collagen accumulation through the ERK signaling pathway.

Conclusions
Our findings first revealed that HOXC6 acts as an oncogenic driver in the molecular mechanisms of fibroblasts in keloids. The HIF-1α/HOXC6/ERK axis promotes proliferation, migration and ECM production by KFs, contributing to the progression of keloids. Taken together, HOXC6 may serve as a promising novel therapeutic target and new focus for research designed to understand the pathogenesis of keloids.
Effectiveness of Messenger RNA–based Vaccines During the Emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant
Authors: Sharma Aditya , Oda Gina , Holodniy Mark 
Published: April 2022

AbstractBackgroundWe evaluated the effectiveness of mRNA-based vaccines following emergence of SARS-CoV-2 Omicron variant.MethodsRecipients of a third dose of BNT162b2 or mRNA-1273 ≥180 days after the primary series were matched to primary-series recipients and unvaccinated persons. Participants were followed from 1 December 2021 to 12 March 2022. Outcomes were documented SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 death. Effectiveness was calculated from 100-day risks estimated with the Kaplan-Meier estimator.ResultsBNT162b2 and mRNA-1273 groups included 221 267 and 187 507 third-dose recipients, respectively, matched to equal numbers of primary-series recipients and unvaccinated persons. Compared with no vaccination, effectiveness of a third dose of BNT162b2 was 47.8% (95% confidence interval [CI], 45.2–50.3), 81.8% (95% CI, 79.2–84.2), and 89.6% (95% CI, 85.0–93.6) against infection, hospitalization, and death, respectively. Effectiveness of a third dose of BNT162b2 compared with the primary series was 30.1% (95% CI, 26.2–33.7), 61.4% (95% CI, 55.0–67.1), and 78.8% (95% CI, 67.9–87.5) against infection, hospitalization, and death, respectively. Effectiveness of a third dose of mRNA-1273 compared with no vaccination was 61.9% (95% CI, 59.4–64.4), 87.9% (95% CI, 85.3–90.2), and 91.4% (95% CI, 86.4–95.6) against infection, hospitalization, and death, respectively. Effectiveness of a third dose of mRNA-1273 compared with the primary series was 37.1% (95% CI, 32.2–41.7), 63.5% (95% CI, 53.7–71.6), and 75.0% (95% CI, 55.4–88.0) against infection, hospitalization, and death, respectively.ConclusionsBNT162b2 and mRNA-1273 were effective against COVID-19 following emergence of Omicron variant. A third dose provided additional protection over the primary series.
Case Series: Re-induction of Intravenous, Weight-Based Ustekinumab Is Well Tolerated in Patients With Moderate–Severe Crohn’s Disease
Authors: Lee Scott David , Kamp Kendra , Clark-Snustad Kindra Dawn 
Published: April 2022

Abstract

Background
Crohn’s disease (CD) patients may benefit from biologic optimization.

Methods
We retrospectively assessed adverse events (AEs) and clinical/endoscopic response after ustekinumab re-induction in CD patients.

Results
We identified 28 patients, all with prior biologic exposure. Eight weeks following re-induction, 10.7% reported ≥1 AE. Three serious AEs occurred in a single patient (CD flares). No infusion reactions occurred. 53.8% and 38.5% achieved clinical response and remission, respectively. 42.8% achieved both endoscopic improvement and remission.

Conclusions
Ustekinumab re-induction was well tolerated. Clinical and endoscopic disease activity improved in some patients. Further larger studies are needed to verify these findings in a broader population.
Inheritance of social dominance is associated with global sperm DNA methylation in inbred male mice
Authors: Hou Guan-Mei , Zhang Yao-Hua , Zhang Jian-Xu 
Published: April 2022

Abstract
Dominance relationships between males and their associated traits are usually heritable and have implications for sexual selection in animals. In particular, social dominance and its related male pheromones are heritable in inbred mice; thus, we wondered whether epigenetic changes due to altered levels of DNA methylation determine inheritance. Here, we used C57BL/6 male mice to establish a social dominance–subordination relationship through chronic dyadic encounters, and this relationship and pheromone covariation occurred in their offspring, indicative of heritability. Through transcriptome sequencing and whole-genome DNA methylation profiling of the sperm of both generations, we found that differential methylation of many genes was induced by social dominance–subordination in sires and could be passed on to the offspring. These methylated genes were mainly related to growth and development processes, neurodevelopment, and cellular transportation. The expression of the genes with similar functions in whole-genome methylation/bisulfite sequencing was also differentiated by social dominance–subordination, as revealed by RNA-seq. In particular, the gene Dennd1a, which regulates neural signaling, was differentially methylated and expressed in the sperm and medial prefrontal cortex in paired males before and after dominance–subordination establishment, suggesting the potential epigenetic control and inheritance of social dominance-related aggression. We suggest that social dominance might be passed on to male offspring through sperm DNA methylation and that the differences could potentially affect male competition in offspring by affecting the development of the nervous system.
Social buffer or avoidance depends on the similarity of stress between queen ants
Authors: Sanmartín-Villar Iago 
Published: April 2022

AbstractThe association of unrelated ant queens (pleometrosis) is supposed to improve nest foundation and competitiveness under environmental stress, but its evolutionary maintenance is difficult to explain because only one of the queens survives after nest foundation. My aim was to test the potential effect of queen association as a social buffer, that is, as a mechanism reducing stress and improving fitness due to the benefits of social contact. I analyzed the survival, fecundity, and behavior of isolated and paired Lasius flavus queens exposed and not exposed to stressors (disturbing environmental conditions). I found no difference in survivorship between isolated and paired queens or between stressed and unstressed isolated queens. Groups in which 1 or 2 paired queens were stressed showed higher mortality. Unstressed queens died similarly to their stressed nestmates, suggesting stress transmission. A trend suggested that paired queens produced eggs more quickly, but eggs were produced similarly between isolated and paired queens. Social avoidance was observed in groups with 1 stressed and 1 unstressed queen. However, the groups with 2 stressed queens showed the expected behaviors according to social buffering: lower mobility and more interindividual inspection. My findings suggest the synergistic effect of pleometrosis and stress and the dependence of stress level similarity between nestmates on social buffering or rejection on ant queens.
Discrimination and Deaf Adolescents’ Subjective Well-Being: The Role of Deaf Identity
Authors: Ma Yidan , Xue Weifeng , Liu Qin , Xu Yin 
Published: April 2022

Abstract
This study tested the influence of Deaf identity (cognitive identification and affective identification) on the association between perceived deaf discrimination and subjective well-being among Chinese adolescents who are deaf and hard-of-hearing (DHH), based on the rejection-identification model. Questionnaires on perceived deaf discrimination, subjective well-being, Deaf identity, and demographic information were completed by 246 DHH students (15–23 years old) from special residential schools in China. The results indicated that: (1) higher level of perceived deaf discrimination was significantly associated with lower level of subjective well-being (direct effect = −0.24, 95% confidence interval [CI] = [−0.37, −0.12], p &lt; .001); (2) there was a significant indirect effect of perceived deaf discrimination on subjective well-being via cognitive identification (indirect effect = −0.07, 95% CI = [−0.12, −0.01], p &lt; .05); and (3) positive affective identification due to increased cognitive identification with Deaf community may help counteract the negative impact of perceived deaf discrimination on subjective well-being (indirect effect = 0.06, 95% CI = [0.03, 0.10], p &lt; .001). These findings further support the notion that the different components of group identification should be examined separately.
Effect of sex and surgical incision on survival after isolated primary mitral valve operations
Authors: Dębski Maciej , Taylor Rebecca , Abdelrahman Amr , Dębska Karolina , Assaf Omar , Qadri Syed , Wong Kenneth Y -K , Vassiliou Vassilios , Zacharias Joseph 
Published: April 2022

Abstract

OBJECTIVES
Multiple studies have suggested that women have worse outcomes than men following mitral valve (MV) surgery—most of those studies reported on conventional sternotomy (CS) MV surgery. Therefore, we aimed to explore whether or not the minimally invasive mitral valve surgery (MIMVS) approach might mitigate a worse survival in women following MV surgery.

METHODS
We identified patients with isolated primary MV operations with or without tricuspid valve repair performed between 2007 and 2019. Patients were propensity score-matched across the MIMVS and CS surgical approaches. Sex was excluded from the matching process to discern whether female patients had a different likelihood of receiving minimally invasive surgery than males. A Cox proportional hazards model was fitted in the matched cohort and adjusted for the imbalance in baseline characteristics using the propensity score.

RESULTS
Of 956 patients (417 MIMVS, 539 CS; 424 females), the matched set comprised 342 pairs (684 patients; 296 females) of patients who were well balanced across MIMVS and CS groups with regard to preoperative clinical characteristics. We observed a 47/53% female/male ratio in the CS group and a 39/61% in the MIMVS group, P = 0.054. In both matched groups, women were older than males. A Cox model adjusted for propensity scores showed no survival difference with sex, surgical type or interaction.

CONCLUSIONS
Women present to the surgical team at an older age. They appear less likely to be considered for a MIMVS approach than men. Neither sex nor surgical approach was associated with worse survival in a matched sample.
Weak Cation Selectivity in HCN Channels Results From K+-Mediated Release of Na+ From Selectivity Filter Binding Sites
Authors: Bauer Daniel , Wissmann Jan , Moroni Anna , Thiel Gerhard , Hamacher Kay 
Published: April 2022

Abstract
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels generate the pacemaker current which plays an important role in the timing of various biological processes like the heart beat. We used umbrella sampling to explore the potential of mean force for the conduction of potassium and sodium through the open HCN4 pore. Our data explain distinct functional features like low unitary conductance and weak selectivity as a result of high energetic barriers inside the selectivity filter of this channel. They exceed the 3-5 kJ/mol threshold which is presumed as maximal barrier for diffusion-limited conductance. Furthermore, simulations provide a thermodynamic explanation for the weak cation selectivity of HCN channels that contain only two ion binding sites in the selectivity filter (SF). We find that sodium ions bind more strongly to the SF than potassium and are easier released by binding of potassium than of another sodium. Hence ion transport and selectivity in HCN channels is not determined by the same mechanism as in potassium-selective channels; it rather relies on sodium as a weak blocker that can only be released by potassium.
Convergent evolution of polyploid genomes from across the eukaryotic tree of life
Authors: Hao Yue , Fleming Jonathon , Petterson Joanna , Lyons Eric , Edger Patrick P , Pires J Chris , Thorne Jeffrey L , Conant Gavin C 
Published: April 2022

AbstractBy modeling the homoeologous gene losses that occurred in 50 genomes deriving from ten distinct polyploidy events, we show that the evolutionary forces acting on polyploids are remarkably similar, regardless of whether they occur in flowering plants, ciliates, fishes, or yeasts. We show that many of the events show a relative rate of duplicate gene loss before the first postpolyploidy speciation that is significantly higher than in later phases of their evolution. The relatively weak selective constraint experienced by the single-copy genes these losses produced leads us to suggest that most of the purely selectively neutral duplicate gene losses occur in the immediate postpolyploid period. Nearly all of the events show strong evidence of biases in the duplicate losses, consistent with them being allopolyploidies, with 2 distinct progenitors contributing to the modern species. We also find ongoing and extensive reciprocal gene losses (alternative losses of duplicated ancestral genes) between these genomes. With the exception of a handful of closely related taxa, all of these polyploid organisms are separated from each other by tens to thousands of reciprocal gene losses. As a result, it is very unlikely that viable diploid hybrid species could form between these taxa, since matings between such hybrids would tend to produce offspring lacking essential genes. It is, therefore, possible that the relatively high frequency of recurrent polyploidies in some lineages may be due to the ability of new polyploidies to bypass reciprocal gene loss barriers.
The role of geotectonic setting on the heat flow distribution of southern South America
Authors: Christiansen Rodolfo O , Gianni Guido M , Ballivián Justiniano Carlos A , García Héctor P A , Wohnlich Stefan 
Published: April 2022

SUMMARYThe surface heat flow of southern South America was examined based on an updated database containing 1113 locations. Accordingly, this study presents the most accurate heat flow map of the southern portion of the continent (south of 16°30′S latitude), covering areas that previously presented limited information. The main anomalies show a strong spatial correlation with geothermal zones and with the most up-to-date lithospheric thickness maps. The blanketing effect produced by the sedimentary basins reduce the surface heat flow up to 27 mW m–2 over the thickest basins. The study region was separated into four large areas and their connection to tectonic processes analysed. The Central Andes present high heat flow zones related to a thick radiogenic crust, volcanic activity, and a hot asthenospheric wedge. In the Pampean flat-slab region, the low heat flow coincides mostly with the horizontal projection of the Juan Fernández aseismic ridge and not with a wide region as previously thought. Furthermore, a close relationship between the subduction of the ridges at different angles and a cold upper-plate lithosphere is suggested. Besides active regions of arc magmatism and a thin lithosphere, we propose that a hot upper-plate upwelling beneath the Patagonian Platform is also contributing to the high heat flow in the area. The foreland region exhibits a low heat flow coinciding with a thick cratonic lithosphere, and local high heat flow values in suture zones possibly triggered by ancient delamination beneath these regions.
LcERF19, an AP2/ERF transcription factor from Litsea cubeba, positively regulates geranial and neral biosynthesis
Authors: Wang Minyan , Gao Ming , Zhao Yunxiao , Chen Yicun , Wu Liwen , Yin Hengfu , Yang Jiahui , Xiong Shifa , Wang Siqi , Wang Jue , Yang Yang , Wang Jia , Wang Yangdong 
Published: April 2022

Abstract
The APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors (TFs) are involved in the regulation of specialized terpenoid biosynthesis. However, the AP2/ERF TFs in Litsea cubeba have not been characterized and their role in the biosynthesis of terpenoids is unknown. Here, 174 LcAP2/ERF TFs were identified in L. cubeba and categorized into four subfamilies: 27 AP2, 7 RAV, 1 Soloist, and 139 ERF. Transcriptomic and qRT-PCR assays both showed that the expression levels of LcERF19 were similar to that of terpene synthase LcTPS42 in the pericarp, which is related to the synthesis of geranial and neral in L. cubeba. LcERF19 was further shown to encode a nuclear-localized protein and its expression was strongly induced by jasmonate. Yeast one-hybrid and dual-luciferase assays showed that LcERF19 associated with GCC box elements of the LcTPS42 promoter and promoted its activity. Transient overexpression of LcERF19 in L. cubeba and overexpression of LcERF19 in tomato resulted in a significant increase in geranial and neral. Our findings show that LcERF19 enhances geranial and neral biosynthesis through activation of LcTPS42 expression, which provides a strategy to improve the flavor of tomato and other fruits.
Development and validation of MicrobEx: an open-source package for microbiology culture concept extraction
Authors: Eickelberg Garrett , Luo Yuan , Sanchez-Pinto L Nelson 
Published: April 2022

Abstract

Objective
Microbiology culture reports contain critical information for important clinical and public health applications. However, microbiology reports often have complex, semistructured, free-text data that present a barrier for secondary use. Here we present the development and validation of an open-source package designed to ingest free-text microbiology reports, determine whether the culture is positive, and return a list of Systemized Nomenclature of Medicine (SNOMED)-CT mapped bacteria.

Materials and Methods
Our concept extraction Python package, MicrobEx, is built upon a rule-based natural language processing algorithm and was developed using microbiology reports from 2 different electronic health record systems in a large healthcare organization, and then externally validated on the reports of 2 other institutions with manually reviewed results as a benchmark.

Results
MicrobEx achieved F1 scores &gt;0.95 on all classification tasks across 2 independent validation sets with minimal customization. Additionally, MicrobEx matched or surpassed our MetaMap-based benchmark algorithm performance across positive culture classification and species capture classification tasks.

Discussion
Our results suggest that MicrobEx can be used to reliably estimate binary bacterial culture status, extract bacterial species, and map these to SNOMED organism observations when applied to semistructured, free-text microbiology reports from different institutions with relatively low customization.

Conclusion
MicrobEx offers an open-source software solution (available on both GitHub and PyPI) for bacterial culture status estimation and bacterial species extraction from free-text microbiology reports. The package was designed to be reused and adapted to individual institutions as an upstream process for other clinical applications such as: machine learning, clinical decision support, and disease surveillance systems.
Pneumomediastinum, Facial Nerve Injury, and Sialocele Secondary to a Firework Burn to the Cheek: A Case Report
Authors: Lambert Raphaella A , Shogan Andrea N , Vrouwe Sebastian Q 
Published: April 2022

AbstractFireworks injuries can result in devastating cutaneous burns and may be further complicated in the head and neck region by the presence of specialized deeper structures. In the United States, the head and neck remain the most commonly injured sites, with the majority of these injuries constituting burns. We present an adult patient who suffered an accidental right cheek burn injury and went on to experience a complex pattern of findings including pneumomediastinum, facial nerve palsy, and sialocele formation.
Current status of endoscopic detection, characterization and staging of superficial esophageal squamous cell carcinoma
Authors: Ishihara Ryu , Muto Manabu 
Published: April 2022

Abstract

Background
This review focuses on the current status of endoscopic detection, characterization and tumour category staging of oesophagealsquamous cell carcinoma.

Detection
The diagnostic yield of white-light imaging is limited and narrow-band imaging has demonstrated a better performance for detecting oesophageal cancer. Narrow-band imaging has also shown similar sensitivity and superior specificity to iodine staining.

Characterization
Accurate differentiation between cancerous and non-cancerous lesions can be achieved by magnifying narrow-band imaging or iodine staining with confirmation of a pink-colour sign. A per-patient analysis of a randomized study showed similar sensitivities, specificities and overall accuracies of magnifying narrow-band imaging and iodine staining of 82.2%, 95.1% and 91.2%, and 80.5%, 94.3% and 90.5%, respectively.

Tumour-staging
The diagnostic capability of endoscopic ultrasonography after conventional and narrow-band imaging in terms of tumour depth was evaluated in a multicentre prospective study. Endoscopic ultrasonography did not significantly improve the accuracy for distinguishing between mucosal or submucosal microinvasive cancer and deeper cancers from 72.9 to 74.0%, suggesting that additional endoscopic ultrasonography did not improve the diagnostic accuracy. In addition, endoscopic ultrasonography increased the incidence of overdiagnosis, defined as a diagnosis of cancer depth greater than the actual depth, by 6.6%. The risk of overdiagnosis by endoscopic ultrasonography was reconfirmed in two systematic reviews.

Conclusions
Narrow-band imaging is currently considered as the standard modality for the detection and characterization of oesophageal cancer. The risk of overdiagnosis should be considered when applying endoscopic ultrasonography for the evaluation of tumour invasion depth of superficial oesophageal squamous cell carcinoma.