bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bipolar high-frequency electric welding in radical resection of frontal sinus tumors
Authors: Zabolotnyi Dmytro , Kvasha Olena 
Published: April 2023

Abstract
The aim of study is to develop a new method of connecting the dura mater (DM) defects in frontal sinus tumors with intracranial spread using high-frequency bipolar coagulation for welding of living tissues. Depending on the method of DM defect repair, patients were divided into two groups. The 1st group (control) included patients whose DM defect was connected according to the conventional method (suturing with polypropylene threads), in the 2nd group—the DM defect was connected by high-frequency bipolar electric welding using EKVZ-300, Patonmed. As a result of the study, the authors proposed an effective method of connecting the DM defects after the removal of frontal sinus tumors spreading intracranially. Such methods include a high-frequency bipolar electric welding method, the use of which contributed to a minimal destructive effect on adjacent tissues, but at the same time hermetically connected the DM. This was possible due to the supply of current with certain wave characteristics in a certain modulation at a temperature of 40–48°C, resulting in the connection of tissues without the formation of a coagulation scab due to the mechanism of protein-associated electrothermal adhesion of tissues. Presented data indicate significant advantages of using high-frequency bipolar electric welding the DM defects and fascia lata to restore the closed physiological circuit of cerebrospinal fluid circulation, compared to the traditional suture method. This approach has reduced intra- and post-operative complications, the time of surgery, and the length of the postoperative period.
Study on flame propagation characteristics of coal dust explosion in horizontal straight pipe
Authors: Song Baichao 
Published: April 2023

AbstractCoal dust explosion is one of the common accidents in mines. The flame generated in the explosion process spreads rapidly, and the high-temperature flame will cause personal injury and equipment damage in the working environment. In order to study the flame propagation characteristics of coal dust explosion, four kinds of coal dust explosion flame propagation experiments were carried out by using the intelligent coal dust explosion identification device, and the flame propagation process was simulated by computational fluid dynamics (CFD) simulation. The results show that the flame length of lignite dust explosion is obviously longer than that of long flame coal, non-caking coal and gas coal. From the ignition of lignite coal dust, the flame length increases continuously, reaches the maximum of 52 cm at a certain time and then gradually decreases to 0. While the flame length increases, the flame propagation rate also experiences the propagation process of accelerating and decelerating. By comparing the explosion flame length obtained by CFD numerical simulation with the experimental results, it is found that the simulation error is within the acceptable range. Further statistical analysis is made on the simulation results of overpressure generated by explosion, and it is found that the change law is consistent with the theoretical formula, so as to further verify the feasibility of numerical simulation for explosion research. The research results lay a theoretical foundation for predicting the disaster scope of coal dust explosion accidents, and have practical significance for taking explosion suppression and flameproof measures in mines.
Functional analysis of rare anti-Müllerian hormone protein-altering variants identified in women with PCOS
Authors: Meng L , McLuskey A , Dunaif A , Visser J A 
Published: April 2023

Abstract
Recently, rare heterozygous AMH protein-altering variants were identified in women with polycystic ovary syndrome (PCOS), causing reduced anti-Müllerian hormone (AMH) signaling. However, the exact functional mechanism remains unknown. Here, we analyzed the processing, secretion, and signaling of these AMH variants. Functional analysis of six PCOS-specific AMH variants (V12G, P151S, P270S, P352S, P362S, H506Q) and one control-specific variant (A519V) was performed in the mouse granulosa cell-line KK-1. Human (h) AMH-151S and hAMH-506Q have ∼90% decreased AMH signaling compared to wild-type (wt) AMH signaling. Coexpression of hAMH-151S or hAMH-506Q with wt-hAMH dose-dependently inhibited wt-hAMH signaling. Western blotting revealed that hAMH-151S and hAMH-506Q proteins were detected in the cell lysate but not in the supernatant. Confocal microscopy showed that HEK293 cells expressing hAMH-151S and hAMH-506Q had higher cellular AMH protein levels with endoplasmic reticulum (ER) retention compared to cells expressing wt-hAMH. Using two AMH ELISA kits, hAMH-151S was detected in the cell lysate, while only very low levels were detected in the supernatant. Both hAMH-362S and hAMH-519V were detectable using the automated AMH ELISA but showed severely reduced immunoactivity in the manual ELISA. Surprisingly, hAMH-506Q was undetectable in both the cell lysate and supernatant using either ELISA. However, in PCOS cases, heterozygous carriers of the P151S and H506Q variants still had detectable AMH in both assays. Thus, P151S and H506Q disrupt normal processing and secretion of AMH, causing ER retention. Additionally, AMH variants can impair the AMH immunoactivity. An AMH variant may be considered when serum AMH levels are relatively low in PCOS cases.
Caudal epidural steroid injection versus transforaminal ESI for unilateral S1 radiculopathy: a prospective, randomized trial
Authors: Ozturk Ekim Can , Sacaklidir Rekib , Sencan Savas , Gunduz Osman Hakan 
Published: April 2023

Abstract

Objective
Epidural steroid injections are frequently performed to manage radicular symptoms. Most research investigating the effectiveness of different routes of epidural injections were conducted with non-homogeneous groups. In this study our aim was to investigate the efficacy of caudal versus transforaminal approaches in patients with unilateral S1 radiculopathy secondary to a paracentral L5–S1 disc herniation.

Study design
Prospective, randomized clinical trial.

Setting
A university hospital pain management center.

Methods
The study was conducted between January 2022 and February 2023. Patients with unilateral S1 radiculopathy were randomly divided into two groups: the caudal epidural steroid injection (CESI) and the transforaminal epidural steroid injection (TFESI) group. Severity of pain and disability were assessed with Numeric Rating Scale (NRS-11) and Oswestry Disability Index (ODI) at baseline, 3 weeks, and 3 months after treatment. Fifty percent or more improvement in NRS-11 was defined as treatment success. Fluoroscopy time and doses of exposed radiation were also recorded.

Results
A total of 60 patients were included in the final analysis (n = 30 for each group). Significant improvement in pain and disability scores was observed at 3rd week and 3rd month compared to baseline (P &lt; .001). Treatment success rate at 3rd month was 77% for the CESI group and 73% for the TFESI group without any significant difference between the groups (P = .766).

Conclusions
CESI is equally effective as TFESI in the management of S1 radiculopathy due to a paracentral L5–S1 disc herniation. Both approaches can reduce pain and disability, while CESI requires shorter fluoroscopy time and less radiation exposure.
Paediatric rheumatologists do not score the physician’s global assessment of juvenile idiopathic arthritis disease activity in the same way
Authors: Backström Maria , Tarkiainen Maarit , Gottlieb Beth S , Trincianti Chiara , Qiu Tingting , Morgan Esi , Lovell Daniel J , Bovis Francesca , Löyttyniemi Eliisa , Ruperto Nicolino , Vähäsalo Paula , Consolaro Alessandro 
Published: April 2023

Abstract

Objectives
To assess the heterogeneity in factors affecting physician’s global assessment of disease activity (PhGA) and in PhGA scoring of multiple JIA patient’s case scenarios.

Methods
An electronic web-based questionnaire of factors potentially considered in PhGA was sent worldwide to members of PRINTO and the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN). The respondents were asked to rate from 0 to 100 the relevance of 17 factors possibly affecting PhGA scoring and to derive a PhGA score of 17 detailed JIA patient cases. The median and interquartile range was used to measure the heterogeneity in the scoring. To demonstrate the consistency among the PhGA scores of the patient cases provided by multiple physicians, we assessed the inter-rater reliability using intra-class correlation.

Results
The questionnaire was completed by 491 respondents. A large individual variation was observed in the impact of different factors on PhGA when assessing JIA. For non-systemic JIA the presence of fever had the largest variation and swollen joint count had the smallest. For sJIA, the largest variation was seen in the presence of erosions and the smallest in the presence of fever. The intra-class correlation of the group for PhGA scoring of patient cases was 0.53 (95% CI 0.38, 0.72).

Conclusions
In a sample of worldwide respondents, the scoring of the PhGA is divergent. Consensus on PhGA scoring guidelines is required to obtain a consistent assessment of patients.
Impact of population size on early adaptation in rugged fitness landscapes
Authors: Servajean Richard , Bitbol Anne-Florence 
Published: April 2023

Owing to stochastic fluctuations arising from finite population size, known as genetic drift, the ability of a population to explore a rugged fitness landscape depends on its size. In the weak mutation regime, while the mean steady-state fitness increases with population size, we find that the height of the first fitness peak encountered when starting from a random genotype displays various behaviours versus population size, even among small and simple rugged landscapes. We show that the accessibility of the different fitness peaks is key to determining whether this height overall increases or decreases with population size. Furthermore, there is often a finite population size that maximizes the height of the first fitness peak encountered when starting from a random genotype. This holds across various classes of model rugged landscapes with sparse peaks, and in some experimental and experimentally inspired ones. Thus, early adaptation in rugged fitness landscapes can be more efficient and predictable for relatively small population sizes than in the large-size limit.
This article is part of the theme issue ‘Interdisciplinary approaches to predicting evolutionary biology’.
SERPINB3 induces the basal-like/squamous subtype and enhances disease progression in pancreatic cancer
Authors: Ohara Yuuki , Tang Wei , Liu Huaitian , Yang Shouhui , Dorsey Tiffany H. , Cawley Helen , Moreno Paloma , Azizian Azadeh , Gaedcke Jochen , Ghadimi B. Michael , Hanna Nader , Ambs Stefan , Hussain S. Perwez 
Published: April 2023

AbstractPancreatic cancer is a heterogeneous disease with distinct subtypes. Here, we investigated candidate driver genes of the highly aggressive basal-like/squamous molecular subtype of pancreatic ductal adenocarcinoma (PDAC). Integrative transcriptomic analyses identified the upregulated serine/cysteine protease inhibitor, SERPINB3 (squamous cell carcinoma antigen 1, SCCA1) in basal-like/squamous PDAC using discovery and validation approaches. Upregulation of SERPINB3 associated with decreased patient survival and a transcriptome profile indicative of the basal-like/squamous subtype. In human PDAC cell lines, SERPINB3 transgene expression enhanced their invasion capability. Moreover, upregulated expression of SERPINB3 in AsPC-1 cells resulted in enhanced lung metastasis in an orthotopic xenograft model. Molecular analysis of the primary tumor xenografts indicated activation of pathways related to metastasis, increased oxidative damage, and angiogenesis when SERPINB3 was upregulated. Furthermore, metabolomic analysis, using patient cohorts and PDAC cell lines showed a distinct metabolic pattern closely associated with both SERPINB3 and the basal-like/squamous subtype, which included upregulation of carnitine/acylcarnitine, amino acid, glutathione, and purine metabolic pathways, and glycolysis. Further RNA-seq and metabolomic analyses indicated that SERPINB3 may potentially induce the basal-like/squamous subtype and metabolic reprogramming through MYC activation. Taken together, our findings identified SERPINB3 as a candidate marker gene for the basal-like/squamous subtype, which may contribute to the disease aggressiveness in this subtype of PDAC.Abbreviations8-Hydroxy-2’-deoxyguanosine (8-OHdG), Diaminobenzene (DAB), Gene Set Enrichment Analysis (GSEA), Human Metabolome Technologies, Inc. (HMT), Immunohistochemistry (IHC), Ingenuity pathway analysis (IPA), Pancreatic ductal adenocarcinoma (PDAC), Serine/Cysteine Proteinase Inhibitor Family B Member 3 (SERPINB3)Graphical abstractHighlightsSERPINB3 is upregulated in basal-like/squamous PDAC and associates with decreased patient survivalSERPINB3 promotes differentiation into the basal-like/squamous subtype and enhances invasion and metastasis of PDACSERPINB3 induces metabolic reprogramming and MYC activation and a metabolic signature indicative of basal-like/squamous PDAC
The structure of the teleost Immunoglobulin M core provides insights on polymeric antibody evolution, assembly, and function
Authors: Lyu Mengfan , Malyutin Andrey G. , Stadtmueller Beth M. 
Published: April 2023

ABSTRACTPolymeric (p) immunoglobulins (Igs) serve broad functions during vertebrate immune responses. Typically, pIgs contain between two and six Ig monomers, each with two antigen binding fragments and one fragment crystallization (Fc). In addition, many pIgs assemble with a joining-chain (JC); however, the number of monomers and potential to include JC varies with species and heavy chain class. Here, we report the cryo-electron microscopy structure of IgM from a teleost (t) species, which does not encode JC. The structure revealed four tIgM Fcs linked through eight C-terminal tailpieces (Tps), which adopt a single β-sandwich-like domain (Tp assembly) located between two Fcs. Remarkably, two of eight heavy chains fold uniquely, resulting in a structure distinct from mammalian IgM, which typically contains five IgM monomers, one JC and a centrally-located Tp assembly. Together with mutational analysis, structural data indicate that pIgs have evolved a range of assembly mechanisms and structures, each likely to support unique antibody effector functions.
Characterization of uranyl (UO22+) ion binding to amyloid beta (Aβ) peptides: effects on Aβ structure and aggregation
Authors: Berntsson Elina , Vosough Faraz , Noormägi Andra , Padari Kärt , Asplund Fanny , Gielnik Maciej , Paul Suman , Jarvet Jüri , Tõugu Vello , Roos Per M. , Kozak Maciej , Gräslund Astrid , Barth Andreas , Pooga Margus , Palumaa Peep , Wärmländer Sebastian K. T. S. 
Published: April 2023

AbstractUranium (U) is naturally present in ambient air, water, and soil, and depleted uranium (DU) is released into the environment via industrial and military activities. While the radiological damage from U is rather well understood, less is known about the chemical damage mechanisms, which dominate in DU. Heavy metal exposure is associated with numerous health conditions including Alzheimer’s disease (AD), the most prevalent age-related cause of dementia. The pathological hallmark of AD is deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils in the brain. However, the toxic species in AD are likely oligomeric Aβ aggregates. Exposure to heavy metals such as Cd, Hg, Mn, and Pb is known to increase Aβ production, and these metals bind to Aβ peptides and modulate their aggregation. Possible effects of U in AD pathology have been sparsely studied. Here, we use biophysical techniques to studyin vitrointeractions between Aβ peptides and uranyl ions, UO22+, of DU. We show for the first time that uranyl ions bind to Aβ peptides with affinities in the micromolar range, induce structural changes in Aβ monomers and oligomers, and inhibit Aβ fibrillization. General toxic mechanisms of uranyl ions could be modulation of protein folding, misfolding, and aggregation.
Characterization of the Root-Associated Microbiome Provides Insights into Endemism ofThymusSpecies Growing in the Kazdagi National Park
Authors: Ercan Gökçe , Arıkan Muzaffer , Yüzbaşıoğlu İ. Sırrı , Yüzbaşıoğlu F. Elif Çepni 
Published: April 2023

AbstractPlant associated microbiomes have a large impact on the fitness of the plants in the particular environmental conditions. The root associated microbiomes are shaped by the interactions between the microbial community members, their plant host, and environmental factors. Hence, further understanding of the composition and functions of the plant root associated microbiomes can pave the way for the development of more effective conservation strategies for endangered endemic plants. Here, we characterized the bacterial and fungal microbiomes in bulk and rhizosphere soil of an endemic and a non-endemicThymusspecies from Kazdagi National Park, Türkiye,Thymus pulvinatusandThymus longicaulissubsp.chaubardii, respectively, by 16S rRNA gene and ITS amplicon sequencing. Our findings revealed no significant differences in alpha diversity between plant species and soil types. However, we found that the bacterial microbiome profiles differentiate not onlyThymusspecies but also soil types while fungal microbiome profiles show distinct profiles particularly between the species in beta diversity.Proteobacteria, Actinobacteria, Acidobacteria, andChlorofleximembers form the core bacterial microbiome while the fungal core microbiome consists ofAscomycotaandBasidiomycotamembers in bothThymusspecies. Moreover, we identified the association of the bacterial taxa contributing to the biogeochemical cycles of carbon and nitrogen and providing the stress resistance with the rhizosphere soil of endemicT. pulvinatus. In addition, functional predictions suggested distinct enriched functions in rhizosphere soil samples of the two plant species. Also, employing an exploratory integrative analysis approach, we determined the plant species-specific nature of transkingdom interactions in twoThymusspecies.
Recombulator-X: a fast and user-friendly tool for estimating X chromosome recombination rates in forensic genetics
Authors: Aneli Serena , Fariselli Piero , Chierto Elena , Bini Carla , Robino Carlo , Birolo Giovanni 
Published: April 2023

AbstractBackground and ObjectiveGenetic markers (especially short tandem repeats or STRs) located on the X chromosome are a valuable resource to solve complex kinship cases in forensic genetics in addition or alternatively to autosomal STRs. Groups of tightly linked markers are combined into haplotypes, thus increasing the discriminating power of tests. However, this approach requires precise knowledge of the recombination rates between adjacent markers.Recombination rates vary across the human genome and cannot be automatically derived from linkage physical maps. The International Society of Forensic Genetics recommends that recombination rate estimation on the X chromosome is performed from pedigree genetic data while taking into account the confounding effect of mutations. However, the only existing implementations that satisfy these requirements have several drawbacks: they were never publicly released, they are very slow and/or need cluster-level hardware and strong computational expertise to use.In order to address these key concerns, we developed Recombulator-X, a new open-source Python tool.MethodsThe most challenging issue, namely the running time, was addressed with dynamic programming techniques to greatly reduce the computational complexity of the algorithm, coupled with JIT compilation to further increase performance. We also extended the statistical framework from STR to any polymorphic marker.ResultsCompared to the previous methods, Recombulator-X reduces the estimation times from weeks or months to less than one hour for typical datasets. Moreover, the estimation process, including preprocessing, has been streamlined and packaged into a simple command-line tool that can be run on a normal PC.Where previous approaches were limited to small panels of STR markers (up to 15), our tool can handle greater numbers (up to 100) of mixed STR and non-STR markers.ConclusionsIn the genetic forensic community, state-of-the-art estimation methods for X chromosome recombination rates have seen limited usage due to the technical hurdles posed by previous implementations. Recombulator-X makes the process much simpler, faster and accessible to researchers without a computational background, hopefully spurring increased adoption of best practices. Moreover, it extends the estimation framework to larger panels of genetic markers (not only STRs), allowing analyses of sequencing-based data.
Dysregulated Wnt and NFAT signaling in a Parkinson’s disease LRRK2 G2019S knock-in model
Authors: Wetzel Andrea , Lei Si Hang , Liu Tiansheng , Hughes Michael P. , Peng Yunan , McKay Tristan , Waddington Simon N. , Grannò Simone , Rahim Ahad A. , Harvey Kirsten 
Published: April 2023

AbstractBackgroundParkinson’s disease (PD) is a progressive late-onset neurodegenerative disease leading to physical and cognitive decline. Mutations of leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of PD. LRRK2 is a complex scaffolding protein with known regulatory roles in multiple molecular pathways. Two prominent examples of LRRK2-modulated pathways are Wingless/Int (Wnt) and nuclear factor of activated T-cells (NFAT) signaling. Both are well described key regulators of immune and nervous system development as well as maturation. The aim of this study was to establish the physiological and pathogenic role of LRRK2 in Wnt and NFAT signaling in the brain, as well as the potential contribution of the non-canonical Wnt/Calcium pathway.MethodsIn vivocerebral Wnt and NFATc1 signaling activity was quantified in LRRK2 G2019S mutant knock-in (KI) and LRRK2 knockout (KO) male and female mice with repeated measures over 28 weeks, employing lentiviral luciferase biosensors, and analyzed using a mixed-effect model. To establish spatial resolution, we investigated tissues, and primary neuronal cell cultures from different brain regions combining luciferase signaling activity, immunohistochemistry, qPCR and western blot assays. Results were analyzed by unpaired t-test with Welch’s correction or 2-way ANOVA with post hoc corrections.ResultsIn vivoWnt signaling activity in LRRK2 KO and LRRK2 G2019S KI mice was increased significantly ∼3-fold, with a more pronounced effect in males (∼4-fold) than females (∼2-fold). NFATc1 signaling was reduced ∼0.5-fold in LRRK2 G2019S KI mice. Brain tissue analysis showed region-specific expression changes in Wnt and NFAT signaling components. These effects were predominantly observed at the protein level in the striatum and cerebral cortex of LRRK2 KI mice. Primary neuronal cell culture analysis showed significant genotype-dependent alterations in Wnt and NFATc1 signaling under basal and stimulated conditions. Wnt and NFATc1 signaling was primarily dysregulated in cortical and hippocampal neurons respectively.ConclusionsOur study further built on knowledge of LRRK2 as a Wnt and NFAT signaling protein. We identified complex changes in neuronal models of LRRK2 PD, suggesting a role for mutant LRRK2 in the dysregulation of NFAT, and canonical and non-canonical Wnt signaling.