bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonbinary and Transgender Male Patient Preferences for Gender-Affirming Top Surgery
Authors: Schafer Rachel E. , Fodor R'ay , Marlar Riley , Jensen Kate K. , Meyers Abigail , Isakov Raymond , Ferrando Cecile , Rampazzo Antonio , Gharb Bahar Bassiri 
Published: July 2024

Background
This study aimed to identify patient preferences and outcomes of chest masculinization surgery in patients identifying as nonbinary versus transgender (trans-) males.

Methods
Patients who underwent chest masculinization (2003–2022) were included. Demographics, medical comorbidities, surgical approaches, complications, secondary procedures, and BODY-Q chest module survey responses were compared between cohorts.

Results
Three hundred two patients were included. Thirteen percent identified as nonbinary and 87% as trans-male. The most common surgical approach in both groups was double incision with free nipple-areola graft (63% vs 71%, P = 0.33). Nonbinary patients more frequently opted for double incision without free nipple areola graft compared to trans-male patients (18% vs 2.7%, P < 0.001). Other unique surgical requests of nonbinary patients included nipple areola preservation and small breast mound preservation (5.2%) and balance between losing bulk and achieving a more androgynous appearance (5.3%). The survey response rate was 31% (93/302). Both groups reported improved quality of life postoperatively (P = 0.16). Three nonbinary patients elected not to keep their nipple-areola complexes (P = 0.005). Trans-male patients were more likely to report having a male chest as very important for their gender identity (82% vs 95%, P = 0.043). Nonbinary patients were less likely to prefer small nipples (82% vs 95%, P = 0.033) and 18% stated that they preferred no nipples (vs 2.7% trans-male patients, P < 0.001).

Conclusions
Nonbinary patients have distinct surgical preferences regarding nipple-areola complexes. Chest masculinization planning can differ for this group of patients compared to their trans-male counterparts.
Evaluation of reported claims of sex-based differences in treatment effects across meta-analyses: A meta-research study
Authors: Kastrati Lum , Farina Sara , Gris Angelica-Valz , Raeisi-Dehkordi Hamidreza , Llanaj Erand , Quezada-Pinedo Hugo G. , Bally Lia , Muka Taulant , Ioannidis John P.A. 
Published: July 2024

ABSTRACTImportanceDifferences in treatment effects between men and women may be important across diverse interventions and diseases.ObjectiveWe aimed to evaluate claims of sex-based differences in treatment effects across published meta-analyses.Data SourcesPubMed (searched up to January 17, 2024).Study SelectionPublished meta-analyses of randomized controlled trials (RCTs) that had any mention of sex (male/female) subgroup or related analysis in their abstract.Data Extraction and SynthesisWe determined how many meta-analyses had made claims of sex-based differences in treatment effects. These meta-analyses were examined in depth to determine whether the claims reflected sex-treatment interactions with statistical support or fallacious claims and categorized the frequency of different fallacies. For claims with statistical support, we examined whether they were considered and discussed in UpToDate. Whenever possible, we re-analyzed the p-value for sex-treatment interaction.Main Outcomes and MeasuresNumber of claims with statistical support and fallacious claims; clinical implications of subgroup differences.Results216 meta-analysis articles fulfilled the eligibility criteria. Of them, 99 stated in the abstract that that there was no sex-based difference, and 20 mentioned a sex-based subgroup analysis without reporting results in the abstract. 97 meta-analyses made 115 claims of sex-based differences. Of them, 27 claims across 21 articles had statistical support at p<0.05. 4/27 claims were mentioned in UpToDate, but none led to different recommendations for men and women. 35 articles had 39 fallacious claims where the sex-treatment interaction was not statistically significant (significant effects in one sex (29 claims in 25 articles), larger effects in one sex (7 claims in 7 articles), other (3 claims in 3 articles)). Another 44 articles made claims based on potentially fallacious methods (39 based on meta-regression of percentage of one group and 5 providing the results of only one group), but proper data were unavailable to assess statistical significance.Conclusions and relevanceFew meta-analyses of RCTs make claims of sex-based differences in treatment effects and most of these claims lack formal statistical support. Statistically significant and clinically actionable sex-treatment interactions may be rare.
Anti-inflammatory effects of electrostimulation
Authors: Di Pietro Biagio , Villata Simona , Dal Monego Simeone , Degasperi Margherita , Ghini Veronica , Guarnieri Tiziana , Plaksienko Anna , Liu Yuanhua , Pecchioli Valentina , Manni Luigi , Tenori Leonardo , Licastro Danilo , Angelini Claudia , Napione Lucia , Frascella Francesca , Nardini Christine 
Published: July 2024

AbstractThe therapeutic usage of physical stimuli is framed in a highly heterogeneous research area, with variable levels of maturity and of translatability into clinical application. In particular, electrostimulation is deeply studied for its application on the autonomous nervous system, but less is known about the anti-inflammatory effects of such stimuli beyond theinflammatory reflex. Further, reproducibility and meta-analyses on existing results are extremely challenging, owing to the limited rationale on dosage and experimental standardization. In this work we propose a series of controlled experiments on the effects of electrical stimuli (in direct and alternate current) delivered on a standardized 3D bioconstruct constituted by fibroblasts and keratinocytes in a collagen matrix. Transcriptomics backed by metabolomics at selected time points allow to obtain a first systematic overview of the biological functions at stake, highlighting the differential anti-inflammatory potential of such approaches, with promising results for 5V direct current stimuli. We hope that our results will trigger an interest and a facilitation in the study of the anti-inflammatory effects of physical stimuli, highlighting not only the potential but also the limitations of such approaches, offering, ultimately, solid evidence for future translation into the clinic.
A microvascularizedin vitroliver model for disease modeling and drug discovery
Authors: Bonanini Flavio , Dinkelberg Roelof , Torregrosa Manuel Caro , Kortekaas Nienke , Hagens Tessa M. S. , Treillard Stéphane , Kurek Dorota , van Duinen Vincent , Vulto Paul , Bircsak Kristin 
Published: July 2024

AbstractDrug discovery for complex liver diseases faces alarming attrition rates. The lack of non-clinical models that recapitulate key aspects of liver (patho)-physiology is likely contributing to the inefficiency of developing effective treatments. Of particular notice is the common omission of an organized microvascular component despite its importance in maintaining liver function and its involvement in the development of several pathologies. Increasing the complexity ofin vitromodels is usually associated with a lack of scalability and robustness which hinders their implementation in drug development pipelines. Here, we describe a comprehensive liver MPS model comprising stellates, liver-derived endothelial cells and hepatocytes conceived within a scalable and automated platform. We show that endothelial cells self-organize in a microvascular network when co-cultured with stellates in a hydrogel. In a tri-culture, hepatocytes polarize accordingly, with a basolateral side facing blood vessels and an apical side facing bile-canaliculi-like structures. Stellates interact and surround the hollow microvessels. Steatosis was induced by exogenous administration of fatty acids which could be prevented by co-administration of firsocostat. Administration of TGF-β resulted in an activated stellate cells phenotype which could be prevented by the co-administration of SB-431542. The model was implemented on a microtiter plate format comprising 64 chips which enabled the development of a fully automated, multiplexed fibrosis assay with a robust Z’ factor suitable for high-throughput applications.
DNA Origami Signal Amplification in Lateral Flow Immunoassays
Authors: Ijäs Heini , Trommler Julian , Nguyen Linh , van Rest Stefan , Nickels Philipp C. , Liedl Tim , Urban Maximilian J. 
Published: July 2024

AbstractLateral flow immunoassays (LFIAs) enable a rapid detection of analytes in a simple, paper-based test format. Despite their multiple advantages, such as low cost and ease of use, their low sensitivity compared to laboratory-based testing limits their use ine.g. many critical point-of-care applications. Here, we present a DNA origami-based signal amplification technology for LFIAs. DNA origami is used as a structurally precise adapter to connect detection antibodies to tailored numbers of signal-generating labels. As a proof of concept, we apply the DNA origami signal amplification in a sandwich-based LFIA for the detection of cardiac troponin I (cTnI) in human serum. We show a 55-fold improvement of the assay sensitivity with 40 nm gold nanoparticle labels and an adjustable signal amplification of up to 125-fold with fluorescent dyes. The technology is compatible with a wide range of existing analytes, labels, and sample matrices, and presents a modular approach for improving the sensitivity and reliability of lateral flow testing.
Diverse effects of fluorescent labels on alpha-synuclein condensate formation during liquid-liquid phase separation
Authors: Ziaunys Mantas , Sulskis Darius , Veiveris Dominykas , Sakalauskas Andrius , Mikalauskaite Kamile , Smirnovas Vytautas 
Published: July 2024

AbstractLiquid-liquid phase separation is an emerging field of study, dedicated to understanding the mechanism and role of biomolecule assembly into membraneless organelles. One of the main methods employed in studying protein and nucleic acid droplet formation is fluorescence microscopy. Despite functioning as an excellent tool for monitoring biomolecule condensation, a few recent reports have presented possible drawbacks of using fluorescently labeled particles. It was observed that fluorescent tags could alter the process of protein liquid-liquid phase separation and even promote their aggregation. In this study, we examined the influence of three different protein labels on alpha-synuclein phase separationin vitroand determined that the changes in droplet formation were related to both the type, as well as concentration of the fluorescently tagged alpha-synuclein. Both protein-based labels (mCherry and eGFP) induced the formation of significantly larger droplets, while fluorescein-tagged alpha-synuclein generated an abundance of small condensates. The study also revealed that alpha-synuclein with protein-based labels could self-associate at much lower concentrations than its untagged counterpart, forming either large droplets or protein aggregates.
Pathogenicity is associated with population structure in a fungal pathogen of humans
Authors: Hatmaker E. Anne , Barber Amelia E. , Drott Milton T. , Sauters Thomas J. C. , Alastruey-Izquierdo Ana , Garcia-Hermoso Dea , Kurzai Oliver , Rokas Antonis 
Published: July 2024

AbstractAspergillus flavusis a clinically and agriculturally important saprotrophic fungus responsible for severe human infections and extensive crop losses. We analyzed genomic data from 250 (95 clinical and 155 environmental)A. flavusisolates from 9 countries, including 70 newly sequenced clinical isolates, to examine population and pan-genome structure and their relationship to pathogenicity. We identified fiveA. flavuspopulations, including a new population, D, corresponding to distinct clades in the genome-wide phylogeny. Strikingly, > 75% of clinical isolates were from population D. Accessory genes, including genes within biosynthetic gene clusters, were significantly more common in some populations but rare in others. Population D was enriched for genes associated with zinc ion binding, lipid metabolism, and certain types of hydrolase activity. In contrast to the major human pathogenAspergillus fumigatus,A. flavuspathogenicity in humans is strongly associated with population structure, making it a great system for investigating how population-specific genes contribute to pathogenicity.
Draft genome ofPalmaria palmataand intraspecific genetic variations in the North-East Atlantic
Authors: Rosignoli Serena , Inaba Masami , Schmid Matthias , McHale Marcus , Fort Antoine , Edwards Maeve D. , Mortensen Agnes Mols , Bartle Roy , Endal Arild , Baud Aurélien , Maggs Christine , Sulpice Ronan 
Published: July 2024

AbstractThe rhodophytePalmaria palmata(L.) Weber & Mohr is one of the target species of a growing European seaweed industry due to its high content of protein and essential amino acids which makes it suitable for human food, dietary supplements, and as salmon feed. However, the lack of a published nuclear genome limits phylogenetics analyses and gene function investigations which could help the development of a breeding programme.We present the first draft genome ofP. palmatathat was obtained with PacBio HiFi long read sequencing with average coverage of 10×, consisting of an assembly of 1.05 Gb, N50=2.75Mb and BUSCO completeness of 72.1%. Additionally, a population study on the whole genome of 33P. palmataindividuals from across the Northern East Atlantic area found three main clusters consistent with their geographic distribution: (1) Denmark and Norway, (2) France and western Ireland, (3) Faroe Islands. All individuals from Northern Ireland share ancestry with western Ireland and Denmark, and some individuals from the Faroe Islands show admixture from Faroe, western Ireland and Northern Ireland. These results represent a fundamental step towards breeding and genetic studies to further explore the vastly unexploited economic potential ofPalmaria palmata.Highlights- We report the first draft genome ofPalmaria palmata, from PacBio HiFi long reads.- The size of the genome, 1.05 Gb, is among the largest so far among the Rhodophyta.- Busco completeness of 72.1% and contig N50 of 2.75 Mb indicate good quality.- The genomes of 33 more individuals from North Atlantic Europe have been sequenced.- Phylogenetic analysis found three clusters consistent with geographic distribution.
Nonergodicity and Simpson’s paradox in neurocognitive dynamics of cognitive control
Authors: Mistry Percy K. , Branigan Nicholas K. , Gao Zhiyao , Cai Weidong , Menon Vinod 
Published: July 2024

AbstractNonergodicity and Simpson’s paradox present significant, yet underappreciated challenges in neuroscience. Leveraging brain imaging and behavioral data from over 4,000 children and a Bayesian computational model of cognitive dynamics, we investigated brain-behavior relationships underlying cognitive control at both between-subjects and within-subjects levels. Strikingly, we observed a reversal of associations of inhibitory control brain activations with dynamic behavioral measures when comparing between-subjects and within-subjects analyses, revealing the nonergodic nature of these processes. This nonergodicity was pervasive throughout the brain but most pronounced in the salience network. Additionally, within-subjects analysis uncovered dissociated brain representations of reactive and proactive control processes, as well as distinct brain-behavior associations for individuals who adaptively versus maladaptively regulated cognitive control. Our findings offer insights into dynamic neural mechanisms of cognitive control during a critical developmental period. This work highlights the importance of embracing nonergodicity in human neuroscience, with implications for both theoretical understanding and applications to AI and psychopathology.
Main sequence of human luminance-evoked pupil dynamics
Authors: Coutinho Jonathan D , Huang Jeff , Lefèvre Philippe , Blohm Gunnar , Munoz Douglas P 
Published: July 2024

AbstractPupil responses are commonly used to provide insight into visual perception, autonomic control, cognition, and various brain disorders. However, making inferences from pupil data can be complicated by nonlinearities in pupil dynamics and variability within and across individuals, which challenge the assumptions of linearity or group level homogeneity required for common analysis methods. In this study, we evaluated luminance evoked pupil dynamics in young healthy adults (N=10, 5:5 M:F, ages 19-25) by identifying nonlinearities, variability, and conserved relationships across individuals to improve the ability to make inferences from pupil data. We found a nonlinear relationship between final pupil diameter and luminance, linearized by considering the logarithm of luminance. Peak diameter change and peak velocity were nonlinear functions of log-luminance for constriction but not dilation responses. Across participants, curve fit parameters characterizing pupil responses as a function of luminance were highly variable, yet there was an across-participant linear correlation between overall pupil size and pupil gain (i.e. diameter change per unit log-luminance change). In terms of within-participant trial-by-trial variability, participants showed greater variability in final pupil size compared to constriction peak diameter change as a function of log-luminance. Despite the variability in stimulus-response metrics within and across participants, we found that all participants showed a highly stereotyped “main sequence” relationship between peak diameter change and peak velocity (independent of luminance). The main sequence relationship can be used to inform models of the neural control of pupil dynamics and as an empirical analysis tool to evaluate variability and abnormalities in pupil behaviour.
Divide and conquer: Using RhizoVision Explorer to aggregate data from multiple root scans using image concatenation and statistical methods
Authors: Seethepalli Anand , Ottley Chanae , Childs Joanne , Cope Kevin , Fine Aubrey K. , Lagergren John , Iversen Colleen M. , Kalluri Udaya , York Larry M. 
Published: July 2024

AbstractRoots are important in agricultural and natural systems for determining plant productivity and soil carbon inputs. The collection of root samples from the field and their subsequent cleaning and scanning in a water-filled tray ranging in size from 5 to 20 cm, followed by digital image analysis has been commonly used since the 1990s for measuring root length, volume, area, and diameter. However, one common issue has been neglected. Sometimes, the amount of roots for a sample is too much to fit into a single scanned image, so the sample is divided among several scans. There is no standard method to aggregate the root measurements across the scans of the same sample. Here, we describe and validate two methods for standardizing measurements across multiple scans: image concatenation and statistical aggregation. Both methods rely on standardizing file naming conventions to identify scans that belong to the same sample. Image concatenation refers to combining digital images into a single larger image while maintaining the original resolution. We developed a Python script that identifies which images belong to the same sample and returns a single, larger concatenated image for every set of images in a directory. These concatenated images (combining up to 10 scans) and the original images were processed with RhizoVision Explorer, a free and open-source software developed for estimating root traits from images, with the same settings. An R script was developed that can identify the rows of data belonging to the same sample in RhizoVision Explorer data files and apply correct statistical methods such as summation, weighted average by length, and average to the appropriate measurement types to return a single data row for each sample. These two methods were compared using example images from switchgrass, poplar, and various tree and ericaceous shrub species from a northern peatland and the Arctic. Overall, the new methods accomplished the goal of standardizing measurement aggregation. Most root measurements were nearly identical except median diameter, which can not be accurately computed by statistical aggregation. We believe the availability of these methods will be useful to the root biology community.
Esophageal epithelialIkkβdeletion promotes eosinophilic esophagitis in experimental allergy mouse model
Authors: Clevenger Margarette H , Wei Cenfu , Karami Adam L , Tsikretsis Lia E , Carlson Dustin A , Pandolfino John E , Gonsalves Nirmala , Winter Deborah R , Whelan Kelly A , Tétreault Marie-Pier 
Published: July 2024

AbstractBackgroundEosinophilic esophagitis (EoE) is a chronic T helper type 2 (Th2)-associated inflammatory disorder triggered by food allergens, resulting in esophageal dysfunction through edema, fibrosis, and tissue remodeling. The role of epithelial remodeling in EoE pathogenesis is critical but not fully understood.ObjectiveTo investigate the role of epithelial IKKβ/NFκB signaling in EoE pathogenesis using a mouse model with conditionalIkkβ knockout in esophageal epithelial cells (IkkβEEC-KO).MethodsEoE was induced inIkkβEEC-KOmice through skin sensitization with MC903/Ovalbumin (OVA) followed by intraesophageal OVA challenge. Histological and transcriptional analyses were performed to assess EoE features. Single-cell RNA sequencing (scRNA-seq) was used to profile esophageal mucosal cell populations and gene expression changes.ResultsIkkβEEC-KO/EoE mice exhibited hallmark EoE features, including eosinophil infiltration, intraepithelial eosinophils, microabscesses, basal cell hyperplasia, and lamina propria remodeling. RNA-seq revealed significant alterations in IKKβ/NFκB signaling pathways, with decreased expression ofRELAand increased expression of IKKβ negative regulators. scRNA- seq analyses identified disrupted epithelial differentiation and barrier integrity, alongside increased type 2 immune responses and peptidase activity.ConclusionOur study demonstrates that loss of epithelial IKKβ signaling exacerbates EoE pathogenesis, highlighting the critical role of this pathway in maintaining epithelial homeostasis and preventing allergic inflammation. TheIkkβEEC-KO/EoE mouse model closely mirrors human EoE, providing a valuable tool for investigating disease mechanisms and therapeutic targets. This model can facilitate the development of strategies to prevent chronic inflammation and tissue remodeling in EoE.Key MessagesCritical Role of Epithelial IKKβ/NFκB Signaling: Loss of this signaling exacerbates EoE, causing eosinophil infiltration, basal cell hyperplasia, and tissue remodeling, highlighting its importance in esophageal health.Molecular Insights and Therapeutic Targets: scRNA-seq identified disrupted epithelial differentiation, barrier integrity, and enhanced type 2 immune responses, suggesting potential therapeutic targets for EoE.Relevance of theIkkβEEC-KO/EoE Mouse Model: This model replicates human EoE features, making it a valuable tool for studying EoE mechanisms and testing treatments, which can drive the development of effective therapies.Capsule SummaryThis study reveals the crucial role of epithelial IKKβ/NFκB signaling in EoE, providing insights into disease mechanisms and potential therapeutic targets, highly relevant for advancing clinical management of EoE.