bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbial Communication via Pyrazine Signaling: A New Class of Signaling Molecules Identified in Vibrio cholerae
Authors: Silpe Justin E. , Duddy Olivia P. , Papenfort Kai 
Published: November 2022

AbstractQuorum sensing is a microbial signaling process that relies on the production, release, and response to extracellular signaling molecules called autoinducers. This Review covers quorum‐sensing systems controlled by a pyrazine‐type autoinducer, 3,5‐dimethyl‐pyrazin‐2‐ol (DPO). The systems we cover span the human pathogen Vibrio cholerae, where DPO regulates pathogenicity and biofilm formation, and phage VP882, where DPO controls lytic development and viral dissemination. In both cases, detection of DPO occurs via a dedicated receptor‐transcription factor called VqmA. In V. cholerae, DPO activates the production of the VqmR regulatory RNA, and in the phage, DPO triggers production of the small protein Qtip. We present our current understanding of DPO biosynthesis, ongoing efforts to resolve the mechanisms underlying DPO‐mediated signal transduction, and a forward‐facing perspective on the role of DPO in human health and undiscovered pyrazine‐based signals in biology, more broadly.
TIGIT-expressing zoledronate-specific γδ T cells display enhanced antitumor activity
Authors: You Hongqin , Zhu Huifang , Zhao Yajie , Guo Jindong , Gao Quanli 
Published: November 2022

AbstractHuman γδ T cells hold a pivotal role in tumor immunosurveillance through their prompt activation and cytokine secretion and have received much attention in adoptive immunotherapy of clear cell renal cell carcinoma (ccRCC). However, the therapeutic effects are limited in ccRCC. Therefore, it is now critical to improve therapeutic strategies based on γδ T cells, especially identification of functional γδ T cell subsets. In this study, we aimed to identify γδ T cells that might have enhanced responses against ccRCC. Bioinformatic analysis showed that ccRCC patients with high T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) expression had higher levels of effector molecules. Then, we examined the changes in the TIGIT+ γδ T cell percentages of 6 ccRCC patients and 14 healthy subjects through zoledronate (ZOL) stimulation. Results indicated that percentages of TIGIT+ γδ T cells were positively correlated with activated γδ T cells in early activation stage. Further study demonstrated that TIGIT+ γδ T cells exhibited enhanced activation, contained more terminally differentiated effector γδ T cells and produced higher cytokine compared with TIGIT- γδ T cells. Finally, we investigated the functions and found that TIGIT+ γδ T cells exhibited stronger tumor reactivities and higher cytotoxicity when challenged by tumor cells. Above results imply that TIGIT+ γδ T cells are the main effectors in ZOL recognition and tumor cells challenging. The results of the present study serve as basis for future functional studies on TIGIT+ γδ T cells and provide a promising approach of immunotherapy in ccRCC.
Infantile primary carnitine deficiency: A severe cardiac presentation unresponsive to carnitine supplementation
Authors: Louis Lebreton , Margaux Gaschignard , Claire Guibet , Delphine Lamireau , Sandrine Roche , Emmanuel Richard , Cécile Ged , Samir Mesli , Isabelle Redonnet‐Vernhet 
Published: November 2022

AbstractPrimary carnitine deficiency (PCD) is an inherited disease of fatty acid beta‐oxidation with autosomal recessive inheritance. The disease manifests as metabolic decompensation with hypoketotic hypoglycaemia associated with cardiomyopathy, hepatomegaly, rhabdomyolysis, and seizures. Various outcomes are described from asymptomatic adults to dramatic sudden infant death syndrome cases. We present a severe case of PCD decompensation in an 18‐week‐old female. She presented with hypotonia, moaning, diarrhea, and vomiting at the pediatric emergency. Initially suspected as intracranial hypertension, the clinical condition evolved rapidly and caused a reversible cardiac arrest with profound hypoglycemia. Despite carnitine supplementation, she succumbed from cardiac arrhythmia and multivisceral failure 4 days after admission. The genetic analyses showed a PCD with biallelic pathogenic variants of SLC22A5 gene. The case report is notable for the severity of the cardiac damage possibly favored by maternal carnitine deficiency during pregnancy. The analysis of previously published PCD cases highlights (i) the importance of having large access to emergency biochemical tests for early therapeutic care although the disease has unpredictable severity and (ii) the fact that the clinical outcome remains unpredictable if carnitine treatment is initiated late.
Temperature‐dependent alcohol acyltransferase reactions as the main enzymatic way to produce short‐chain (C4–C8) and medium‐chain (C9–C13) esters over the whole Daqu‐making process
Authors: Wang Yan , Du Yake , Jin Xuelian , Xia Yu , Zhao Yajiao , Wu Zhengyun , Gomi Katsuya , Zhang Wenxue 
Published: November 2022

AbstractBACKGROUNDThe ester‐synthesis enzymes influenced by environmental factors during Daqu‐making process largely determine the flavor of Chinese liquor, but the main ester‐synthesis enzyme and its key influencer remain unclear. Here, the volatile ester profiles over the whole Daqu‐making process, under different treatments, for at least 90 days, were carefully analyzed, and the potential ester‐synthesis enzymes, as well as their dependently environmental factors, were explored.RESULTSIn the detected 46 volatile esters, only the short‐chain (C4–C8) and medium‐chain (C9–C13) ester content obviously changed, as the primary contributor discriminating different samples. Their trends were both consistent with that of the alcohols and the primary metabolism, which included alcohol acyltransferases (AATs) reaction with alcohols and acyl‐CoAs as the substrates. Among the potential ester‐synthesis enzymes, the typical AAT activity also exhibited the highest correlation with the short‐ and medium‐chain esters (r > 0.78, P < 0.05). The Mantel test between environmental factors and ester production showed that temperature of Daqu was directly correlated with the short‐chain esters (r = 0.58, P < 0.01) and AAT activity (r = 0.56, P < 0.01). Further, the short‐ and medium‐chain ester content in Daqu under the treatment nearer to the reported optimal temperature of 40–50 °C of AATs reaction was overall higher than that of the other treatment Daqu.CONCLUSIONThis study revealed that the temperature‐dependent AATs reaction was the main enzymatic method producing the short‐ and medium‐chain esters over the whole Daqu‐making process. The results could contribute to the flavor improvement of Baijiu. © 2022 Society of Chemical Industry.
Capn4 regulates Snail to promote the epithelial–mesenchymal transition of nasopharyngeal carcinoma by mediating the transcriptional activity of claudin‐11
Authors: Yang Feng , Wang Feng , Gao Ze‐Shou , Quang Guang‐Qian , Hu Hai‐Bei , Zheng Ming 
Published: November 2022

AbstractThe metastasis and recurrence of nasopharyngeal carcinoma (NPC) contribute to the poor prognosis of patients. Inhibiting epithelial–mesenchymal transition (EMT) is an effective strategy to obstruct metastasis. Therefore, this study aimed to explore the effects of Capn4 on the EMT of NPC cells and its specific mechanism of action. The mRNA and protein expression levels of objective genes in NPC cell lines (5‐8F and CNE‐2) were evaluated by qRT‐PCR and western blotting methods. The subcellular localization of Capn4 was detected by immunofluorescence (IF). Migration and invasion abilities of NPC cells were examined via wound‐healing and trans‐well methods, and the linkage between Snail and its downstream effector gene (claudin‐11) was validated by chromatin immunoprecipitation (ChIP), dual‐luciferase, and the yeast one‐hybrid assays in series. Over‐expression of Capn4 activated the PI3K/AKT signaling pathway and improved the expression of Snail, thus promoting the migration and invasion abilities of NPC cells. Mechanically, claudin‐11 is one of the target genes in NPC cells that Snail regulates in a transcriptional regulatory manner. By blocking the regulatory axis of CAPN4/AKT/Snail/claudin‐11 can significantly inhibit the invasion and metastasis of NPC cells. Capn4 promoted the EMT of NPC cells by activating the PI3K/AKT/Snail/claudin‐11 axis, thereby promoting the malignant development of NPC. The Capn4/PI3K/AKT/Snail/claudin‐11 axis might be a novel target to prevent NPC progression.
Posisep Versus PureRegen Gel for Post ESS Nasal Packing – A Randomized Blinded Prospective Study
Authors: Chen Itay , Gete Maru , Sichel Jean Yves , Forer Boaz 
Published: November 2022

ObjectiveEndoscopic sinus surgery (ESS) is the procedure of choice for chronic rhinosinusitis (CRS). Adhesions are the most common postoperative complications, causing recurrent disease and revision surgery. Postoperative care is thus essential for the healing of the operated cavity. A wide variety of packing materials are used to prevent bleeding and adhesions postoperatively. Two main absorbable packing materials are used: Foam‐based packs (e.g., Posisep and Nasopore) and gel‐based packs (PureRegen Gel – PRG). The current study is a randomized, blinded, prospective analysis of cavity healing using Posisep and PRG in ESS, aiming to compare the pros and cons of the two.MethodsPatients with bilateral symmetric CRS were recruited for the study. At the end of surgery, one side was randomly packed with Posisep, whereas the other was packed with PRG. The postoperative cavity cleaning was video recorded and a blinded physician evaluated the mucosal healing.ResultsThe side packed with Posisep had significantly less middle turbinate (MT) lateralization and adhesions yet dissolved significantly slower than the PRG, causing more mucosal edema. Severe MT scarring requiring recurrent medialization and adhesiolysis was exclusively observed in the PRG group. All differences were observed in the early postoperative period (up to 12 weeks after surgery). By that time, only the MT position was significantly different between groups, despite recurrent adhesiolysis and medialization.ConclusionThe authors recommend using Posisep for MT support only when it is unstable or lateralized. Packing the surgical cavity in other cases with PRG is more beneficial.Level of Evidence2 Laryngoscope, 133:1834–1838, 2023
Ultrasonographic Features of Salivary Glands after Radioiodine Therapy in Patients with Thyroid Cancer
Authors: Tsur Nir , Avishai Gal , Alkan Uri , Hod Roy , Shpitzer Thomas , Bitton Eden , Gilat Hanna 
Published: November 2022

ObjectiveChronic sialadenitis is the most common complication of radioactive iodine (RAI) treatment. The aim of the study was to ascertain sonographic features of the major salivary glands in patients with papillary thyroid cancer (PTC) treated with RAI.MethodsThe database of a tertiary medical center was retrospectively searched for consecutive patients who underwent total thyroidectomy for PTC in 2011–2020 with ultrasound follow‐up after 1 year. Changes in ultrasound features of the major salivary glands were compared between patients treated or not treated with RAI postoperatively.ResultsThe cohort included 158 patients, of whom 109 (69%) were treated postoperatively with RAI (mean dose, 131 mCi) and 49 were not (control group). Sonographic changes were observed in the major salivary glands in 43% of the study group and 18% of the control group (p = 0.002), including coarse echotexture, decreased echogenicity, fibrosis, and atrophy. Higher RAI doses were significantly correlated with the prevalence and severity of glandular changes (p < 0.0001).ConclusionRAI treatment following thyroidectomy is associated with a dose–response effect and adverse changes in the major salivary glands and should be prescribed carefully.Level of Evidence4 Laryngoscope, 133:1271–1275, 2023
Sampling uncertainties of particle size distributions and derived fluxes
Authors: Bisson Kelsey M. , Kiko Rainer , Siegel David A. , Guidi Lionel , Picheral Marc , Boss Emmanuel , Cael B. B. 
Published: November 2022

AbstractIn this study, we provide a method to quantify the uncertainty associated with sampling particle size distributions (PSD), using a global compilation of Underwater Vision Profiler observations (UVP, version 5). The UVP provides abundant in situ data of the marine PSD on global scales and has been used for a diversity of applications, but the uncertainty associated with its measurements has not been quantified, including how this uncertainty propagates into derived products of interest. We model UVP sampling uncertainty using Bayesian Poisson statistics and provide formulae for the uncertainty associated with a given sampling volume and observed particle count. We also model PSD observations using a truncated power law to better match the low concentration associated with rare large particles as seen by the UVP. We use the two shape parameters from this statistical model to describe changes in the PSD shape across latitude band, season, and depth. The UVP sampling uncertainty propagates into an uncertainty for modeled carbon flux exceeding 50%. The statistical model is used to extend the size interval used in a PSD‐derived carbon flux model, revealing a high sensitivity of the PSD‐derived flux model to the inclusion of small particles (80–128 μm). We provide avenues to address additional uncertainties associated with UVP‐derived carbon flux calculations.
Synthetic dyes: A mass spectrometry approach and applications
Authors: Millbern Zoe , Trettin Alison , Wu Rachel , Demmler Morgan , Vinueza Nelson R. 
Published: November 2022

AbstractSynthetic dyes are found in a wide variety of applications today, including but not limited to textiles, foods, and medicine. The analysis of these molecules is pertinent to several fields such as forensics, environmental monitoring, and quality control, all of which require the sensitivity and selectivity of analysis provided by mass spectrometry (MS). Recently, there has been an increase in the implementation of MS evaluation of synthetic dyes by various methods, with the majority of research thus far falling under electrospray ionization and moving toward direct ionization methods. This review covers an overview of the chemistry of synthetic dyes needed for the understanding of MS sample preparation and spectral results, current fields of application, ionization methods, and fragmentation trends and works that have been reported in recent years.
Forecasting extreme precipitation in the central Mediterranean: Changes in predictors' strength with prediction lead time
Authors: Mastrantonas Nikolaos , Furnari Luca , Magnusson Linus , Senatore Alfonso , Mendicino Giuseppe , Pappenberger Florian , Matschullat Jörg 
Published: November 2022

AbstractThis work compares forecasting strategies for improving the prediction of extreme precipitation events at different timescales. Our study focuses on forecasting extreme precipitation in Calabria, southern Italy. This region with complex and abruptly varying topography poses additional challenges in forecasting precipitation. Here, we use gridded observational precipitation data from the E‐OBS dataset, reanalysis data from ERA5, and forecasts from ECMWF reforecasts. We show that different forecasting horizons require different forecasting strategies. For short to medium‐range lead times, post‐processing the forecasted extreme precipitation probabilities provides the most informative outputs for end users. For extended‐range forecasts though, it is beneficial to use the large‐scale weather variability, as depicted based on nine Mediterranean patterns in combination with moisture‐related information, to infer reliable information about extreme precipitation. We present benefits and limitations of the methods based on long‐term statistical analysis using a range of indicators, such as the Brier skill score and its decomposition, and the cost–loss model.
Chinese familial central precocious puberty with hyperuricemia due to recurrent DLK1 mutation: Case report and review of the literature
Authors: Yuan Gaopin , Zhang Xiaohong , Liu Shaofeng , Chen Tingli 
Published: November 2022

AbstractBackgroundCentral precocious puberty (CPP) is a precocious puberty due to premature activation of the hypothalamic–pituitary‐gonadal axis (HPG). MKRN3 defects are well‐known causes of CPP, while DLK1 mutations were recently identified in a few patients with CPP.MethodsThe study was approved by the Institutional Review and the scientific committee of the hospital. The clinical data were collected. Whole‐exome sequencing (WES) was performed to detect causative variants. Key words ‘DLK1’, ‘MKRN3’, and “central precocious puberty” were used for literature search in PubMed, Google Scholar, HGMD, and OMIM databases.ResultsThe patient, a male, whose puberty began before age nine, had significant metabolic abnormalities including overweight, hyperlipidemia, and hyperuricemia. WES detected a recurrent frame‐shift mutation, NM_003836.5:c.479delC(p.P160fs*50) in DLK1 in the patient and his father.ConclusionThe familial DLK1‐CPP was identified in China for the first time, which supported that short stature is predicted in patients with CPP without GnRHa treatment. Therefore, we recommend that children with DLK1‐CPP should be treated as early as possible to improve adult height. The patient in this study had persistent hyperuricemia, further suggests that this antiadipogenic factor represents a link between reproduction and metabolism.
Exploring trade‐offs in treatment planning for brain tumor cases with a probabilistic definition of the clinical target volume
Authors: Buti Gregory , Shusharina Nadya , Ajdari Ali , Sterpin Edmond , Bortfeld Thomas 
Published: November 2022

AbstractPurposeThis study demonstrates how a novel probabilistic clinical target volume (CTV) concept—the clinical target distribution (CTD)—can be used to navigate the trade‐off between target coverage and organ sparing with a semi‐interactive treatment planning approach.MethodsTwo probabilistic treatment planning methods are presented that use tumor probabilities to balance tumor control with organ‐at‐risk (OAR) sparing. The first method explores OAR dose reduction by systematically discarding of CTD voxels with an unfavorable dose‐to‐probability ratio from the minimum dose coverage objective. The second method sequentially expands the target volume from the GTV edge, calculating the CTD coverage versus OAR sparing trade‐off after dosing each expansion. Each planning method leads to estimated levels of tumor control under specific statistical models of tumor infiltration: an independent tumor islets model and contiguous circumferential tumor growth model. The methods are illustrated by creating proton therapy treatment plans for two glioblastoma patients with the clinical goal of sparing the hippocampus and brainstem. For probabilistic plan evaluation, the concept of a dose‐expected–volume histogram is introduced, which plots the dose to the expected tumor volume considering tumor probabilities.ResultsBoth probabilistic planning approaches generate a library of treatment plans to interactively navigate the planning trade‐offs. In the first probabilistic approach, a significant reduction of hippocampus dose could be achieved by excluding merely 1% of CTD voxels without compromising expected tumor control probability (TCP) or CTD coverage: the hippocampus dose reduces with 9.5 and 5.3 Gy for Patient 1 and 2, while the TCP loss remains below 1%. Moreover, discarding up to 10% of the CTD voxels does not significantly diminish the expected CTD dose, even though evaluation with a binary volume suggests poor CTD coverage. In the second probabilistic approach, the expected CTD and TCP depend more strongly on the extent of the high‐dose region: the target volume margin cannot be reduced by more than 2 mm if one aims at keeping the expected CTD loss and TCP loss under 1 Gy and 2%, respectively. Therefore, there is less potential for improved OAR sparing without compromising TCP or expected CTD coverage.ConclusionsThis study proposes and implements treatment planning strategies to explore trade‐offs using tumor probabilities.
Modeling of Diffusive Transport of Polymers Moments Using Limiting Cases of the Maxwell–Stefan Model
Authors: Welzel Stefan , Säckel Winfried , Nieken Ulrich 
Published: November 2022

AbstractA polymer distribution is usually represented by its moments. Thus, to calculate transport in a polymer system, a formulation for the transport of moments of the polymer is needed. This is only possible if the moments close or if there is a suitable closing condition. To archive this, two simplifications of the Stefan–Maxwell diffusion are derived, which convert the transport equation of polymeric species to a closed set of transport equations for the polymer moments. The first approach corresponds to an infinitely diluted polymer system, whereas the second one describes a highly concentrated polymer system. Both formulations are compared with the full Stefan‐Maxwell model of a ternary mixture of a solvent and two polymer species of different chain length.
Simultaneous Optimization of MP2RAGE T1‐weighted (UNI) and FLuid And White matter Suppression (FLAWS) brain images at 7T using Extended Phase Graph (EPG) Simulations
Authors: Dokumacı Ayşe Sıla , Aitken Fraser R. , Sedlacik Jan , Bridgen Pip , Tomi‐Tricot Raphael , Mooiweer Ronald , Vecchiato Katy , Wilkinson Tom , Casella Chiara , Giles Sharon , Hajnal Joseph V. , Malik Shaihan J. , O'Muircheartaigh Jonathan , Carmichael David W. 
Published: November 2022

PurposeThe MP2RAGE sequence is typically optimized for either T1‐weighted uniform image (UNI) or gray matter–dominant fluid and white matter suppression (FLAWS) contrast images. Here, the purpose was to optimize an MP2RAGE protocol at 7 Tesla to provide UNI and FLAWS images simultaneously in a clinically applicable acquisition time at <0.7 mm isotropic resolution.MethodsUsing the extended phase graph formalism, the signal evolution of the MP2RAGE sequence was simulated incorporating T2 relaxation, diffusion, RF spoiling, and B1+ variability. Flip angles and TI were optimized at different TRs (TRMP2RAGE) to produce an optimal contrast‐to‐noise ratio for UNI and FLAWS images. Simulation results were validated by comparison to MP2RAGE brain scans of 5 healthy subjects, and a final protocol at TRMP2RAGE = 4000 ms was applied in 19 subjects aged 8–62 years with and without epilepsy.ResultsFLAWS contrast images could be obtained while maintaining >85% of the optimal UNI contrast‐to‐noise ratio. Using TI1/TI2/TRMP2RAGE of 650/2280/4000 ms, 6/8 partial Fourier in the inner phase‐encoding direction, and GRAPPA factor = 4 in the other, images with 0.65 mm isotropic resolution were produced in <7.5 min. The contrast‐to‐noise ratio was around 20% smaller at TRMP2RAGE = 4000 ms compared to that at TRMP2RAGE = 5000 ms; however, the 20% shorter duration makes TRMP2RAGE = 4000 ms a good candidate for clinical applications example, pediatrics.ConclusionFLAWS and UNI images could be obtained in a single scan with 0.65 mm isotropic resolution, providing a set of high‐contrast images and full brain coverage in a clinically applicable scan time. Images with excellent anatomical detail were demonstrated over a wide age range using the optimized parameter set.