bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sexual health and serotonin 4 receptor brain binding in unmedicated patients with depression—a NeuroPharm study
Authors: Rasmussen Annika Læbo , Larsen Søren Vinther , Ozenne Brice , Köhler-Forsberg Kristin , Stenbæk Dea Siggaard , Jørgensen Martin Balslev , Giraldi Annamaria , Frokjaer Vibe G. 
Published: July 2023

AbstractSexual dysfunction is prominent in Major Depressive Disorder (MDD) and affects women with depression more than men. Patients with MDD relative to healthy controls have lower brain levels of the serotonin 4 receptor (5-HT4R), which is expressed with high density in the striatum, i.e. a key hub of the reward system. Reduced sexual desire is putatively related to disturbed reward processing and may index anhedonia in MDD. Here, we aim to illuminate plausible underlying neurobiology of sexual dysfunction in unmedicated patients with MDD. We map associations between 5-HT4R binding, as imaged with [11C]SB207145 PET, in the striatum, and self-reported sexual function. We also evaluate if pre-treatment sexual desire score predicts 8-week treatment outcome in women. From the NeuroPharm study, we include 85 untreated MDD patients (71% women) who underwent eight weeks of antidepressant drug treatment. In the mixed sex group, we find no difference in 5-HT4R binding between patients with sexual dysfunction vs normal sexual function. However, in women we find lower 5-HT4R binding in the sexual dysfunctional group compared to women with normal sexual function (β = −0.36, 95%CI[−0.62:−0.09], p = 0.009) as well as a positive association between sexual desire and 5-HT4R binding (β = 0.07, 95%CI [0.02:0.13], p = 0.012). Sexual desire at baseline do not predict treatment outcome (ROC curve AUC = 52%[36%:67%]) in women. Taken together, we find evidence for a positive association between sexual desire and striatal 5-HT4R availability in women with depression. Interestingly, this raises the question if direct 5-HT4R agonism can target reduced sexual desire or anhedonia in MDD.
Effect of silver diamine fluoride/potassium iodide treatment on the prevention of dental erosion in primary teeth: an in vitro study
Authors: Gadallah Lamia Khairy , Safwat Engie Mohamed , Saleh Reham Sayed , Azab Shereen Musa , Azab Maha Moussa 
Published: July 2023

Abstract
Introduction
Dental erosion has a great effect on oral health, when diagnosed it is irreversible, this sets the importance of different preventive measures being investigated against dental erosion.

Aim
This in vitro study aims to evaluate the effectiveness of silver diamine fluoride and Potassium iodide (SDF-KI) in comparison to casein phosphopeptide-amorphous calcium phosphate fluoride (CPP-ACPF) varnish, sodium fluoride (NaF) varnish, silver diamine fluoride (SDF) alone and deionized water as a control group in the prevention of dental erosion in primary teeth and assessing its staining effect.

Materials and methods
Forty deciduous teeth enamel specimens were randomly allocated into the five study groups. Tested materials were applied. An erosive challenge was done by immersing the specimens in a citric acid-containing soft drink with pH 2.85, for 5 min, 4 times/day, for 5 days. Changes in surface microhardness, mineral loss, and color change were evaluated besides recording of the surface topography and surface roughness for selected specimens.

Results
The highest decrease in surface microhardness was recorded in the control group (−85.21 ± 10.60%), with a statistically significant difference (p = 0.002). SDF-KI group (−61.49 ± 21.08%) showed no statistically significant difference when compared to CPP-ACPF, NaF, and SDF groups. For calcium and phosphorous loss, control group was statistically significantly higher compared to the treatment groups (p = 0.003) and (p < 0.001) respectively, while there was no statistically significant difference between the tested treatment groups. The highest mean value for color change was recorded in SDF group (26.26 ± 10.31), followed by SDF-KI group (21.22 ± 12.87) with no statistically significant difference between groups.

Conclusions
SDF-KI is as effective as CPP-ACPF, NaF varnishes and SDF in the prevention of dental erosion in primary teeth, there was no statistically significant difference regarding its staining potential.
Diacylglycerol lipase alpha promotes hepatocellular carcinoma progression and induces lenvatinib resistance by enhancing YAP activity
Authors: Yan Yu-Chuan , Meng Guang-Xiao , Yang Chun-Cheng , Yang Ya-Fei , Tan Si-Yu , Yan Lun-Jie , Ding Zi-Niu , Ma Yun-Long , Dong Zhao-Ru , Li Tao 
Published: July 2023

AbstractAs an important hydrolytic enzyme that yields 2-AG and free fatty acids, diacylglycerol lipase alpha (DAGLA) is involved in exacerbating malignant phenotypes and cancer progression, but the role of the DAGLA/2-AG axis in HCC progression remains unclear. Here, we found that the upregulation of components of the DAGLA/2-AG axis in HCC samples is correlated with tumour stage and patient prognosis. In vitro and in vivo experiments demonstrated that the DAGLA/2-AG axis promoted HCC progression by regulating cell proliferation, invasion and metastasis. Mechanistically, the DAGLA/2AG axis significantly inhibited LATS1 and YAP phosphorylation, promoted YAP nuclear translocation and activity, and ultimately led to TEAD2 upregulation and increased PHLDA2 expression, which could be enhanced by DAGLA/2AG-induced activation of the PI3K/AKT pathway. More importantly, DAGLA induced resistance to lenvatinib therapy during HCC treatment. Our study demonstrates that inhibiting the DAGLA/2-AG axis could be a novel therapeutic strategy to inhibit HCC progression and enhance the therapeutic effects of TKIs, which warrant further clinical studies.
Effectiveness and safety of XEN45 implant over 12 months of follow-up: data from the XEN-Glaucoma Treatment Registry
Authors: Oddone Francesco , Roberti Gloria , Giammaria Sara , Posarelli Chiara , Ghirelli Giorgio , Mastropasqua Leonardo , Agnifili Luca , Micelli Ferrari Tommaso , Pace Vincenzo , Nucci Paolo , Sacchi Matteo , Monsellato Gianluca , Altafini Romeo , Scuderi Gianluca , Perdicchi Andrea , Uva Maurizio , Carnevale Carmela , Covello Giuseppe , Maglionico Maria Novella , Fea Antonio , Figus Michele 
Published: July 2023

Abstract
Objectives
To evaluate the 1-year effectiveness and safety of the XEN45, either alone or in combination with phacoemulsification, in glaucoma patients.

Methods
This multicentre, prospective, observational study included consecutive eyes of glaucoma patients from the Italian XEN-Glaucoma Treatment Registry (XEN-GTR) who underwent XEN45 alone or in combination with phacoemulsification, with at least 1 year of follow-up. Surgical success was defined as intraocular pressure (IOP) < 18 mmHg and ≥20% reduction from preoperative IOP, over 1 year of follow-up.

Results
Two hundred thirty-nine eyes (239 patients) were analyzed, 144 (60.2%) eyes in the XEN-solo and 95 (39.8%) eyes in the XEN+Phaco groups. One hundred-sixty-eight (70.3%) eyes achieved overall success, without statistically significant differences between study groups (p = 0.07). Preoperative IOP dropped from a median (IQR) of 23.0 (20.0–26.0) mmHg to 14.0 (12.0–16.0) mmHg at month 12 (p < 0.001), with overall 39.9 ± 18.3% IOP reduction. The mean number of preoperative ocular hypotensive medications (OHM) was significantly reduced from 2.7 ± 0.9 to 0.5 ± 0.9 at month 12 (p < 0.001). Preoperative IOP < 15 mmHg (HR: 6.63; 95%CI: 2.61–16.84, p < 0.001) and temporal position of the surgeon (HR: 4.25; 95%CI: 2.62–6.88, p < 0.001) were significantly associated with surgery failure. One hundred-forty-six (61.1%) eyes had no intraoperative complications, whereas 91 (38.1%) and 56 (23.4%) eyes experienced at least one complication, respectively early (< month 1) and late (≥ month 1), all self-limiting or successfully treated without sequelae. Needling occurred in 55 (23.0%) eyes at least once during follow-up.

Conclusion
Over 1-year follow-up, XEN45 alone or in combination with phacoemulsification, had comparable success rates and effectively and safely lowered IOP and the need for OHM.
A mid-Cambrian tunicate and the deep origin of the ascidiacean body plan
Authors: Nanglu Karma , Lerosey-Aubril Rudy , Weaver James C. , Ortega-Hernández Javier 
Published: July 2023

AbstractTunicates are an evolutionarily significant subphylum of marine chordates, with their phylogenetic position as the sister-group to Vertebrata making them key to unraveling our own deep time origin. Tunicates greatly vary with regards to morphology, ecology, and life cycle, but little is known about the early evolution of the group, e.g. whether their last common ancestor lived freely in the water column or attached to the seafloor. Additionally, tunicates have a poor fossil record, which includes only one taxon with preserved soft-tissues. Here we describe Megasiphon thylakos nov., a 500-million-year-old tunicate from the Marjum Formation of Utah, which features a barrel-shaped body with two long siphons and prominent longitudinal muscles. The ascidiacean-like body of this new species suggests two alternative hypotheses for early tunicate evolution. The most likely scenario posits M. thylakos belongs to stem-group Tunicata, suggesting that a biphasic life cycle, with a planktonic larva and a sessile epibenthic adult, is ancestral for this entire subphylum. Alternatively, a position within the crown-group indicates that the divergence between appendicularians and all other tunicates occurred 50 million years earlier than currently estimated based on molecular clocks. Ultimately, M. thylakos demonstrates that fundamental components of the modern tunicate body plan were already established shortly after the Cambrian Explosion.
Important role of endogenous microbial symbionts of fish gills in the challenging but highly biodiverse Amazonian blackwaters
Authors: François-Étienne Sylvain , Nicolas Leroux , Eric Normandeau , Jaqueline Custodio , Pierre-Luc Mercier , Sidki Bouslama , Aleicia Holland , Danilo Barroso , Luis Val Adalberto , Nicolas Derome 
Published: July 2023

AbstractAmazonian blackwaters are extremely biodiverse systems containing some of Earth’s most naturally acidic, dissolved organic carbon -rich and ion‐poor waters. Physiological adaptations of fish facing these ionoregulatory challenges are unresolved but could involve microbially-mediated processes. Here, we characterize the physiological response of 964 fish-microbe systems from four blackwater Teleost species along a natural hydrochemical gradient, using dual RNA-Seq and 16 S rRNA of gill samples. We find that host transcriptional responses to blackwaters are species-specific, but occasionally include the overexpression of Toll-receptors and integrins associated to interkingdom communication. Blackwater gill microbiomes are characterized by a transcriptionally-active betaproteobacterial cluster potentially interfering with epithelial permeability. We explore further blackwater fish-microbe interactions by analyzing transcriptomes of axenic zebrafish larvae exposed to sterile, non-sterile and inverted (non-native bacterioplankton) blackwater. We find that axenic zebrafish survive poorly when exposed to sterile/inverted blackwater. Overall, our results suggest a critical role for endogenous symbionts in blackwater fish physiology.
Ultrasensitive mechanical/thermal response of a P(VDF-TrFE) sensor with a tailored network interconnection interface
Authors: Li Bo , Cai Chuanyang , Liu Yang , Wang Fang , Yang Bin , Li Qikai , Zhang Pengxiang , Deng Biao , Hou Pengfei , Liu Weishu 
Published: July 2023

AbstractFerroelectric polymers have great potential applications in mechanical/thermal sensing, but their sensitivity and detection limit are still not outstanding. We propose interface engineering to improve the charge collection in a ferroelectric poly(vinylidene fluoride-co-trifluoroethylene) copolymer (P(VDF-TrFE)) thin film via cross-linking with poly(3,4-ethylenedioxythiophene) doped with polystyrenesulfonate (PEDOT:PSS) layer. The as-fabricated P(VDF-TrFE)/PEDOT:PSS composite film exhibits an ultrasensitive and linear mechanical/thermal response, showing sensitivities of 2.2 V kPa−1 in the pressure range of 0.025–100 kPa and 6.4 V K−1 in the temperature change range of 0.05–10 K. A corresponding piezoelectric coefficient of −86 pC N−1 and a pyroelectric coefficient of 95 μC m−2 K−1 are achieved because more charge is collected by the network interconnection interface between PEDOT:PSS and P(VDF-TrFE), related to the increase in the dielectric properties. Our work shines a light on a device-level technique route for boosting the sensitivity of ferroelectric polymer sensors through electrode interface engineering.
A spatio-temporal analysis investigating completeness and inequalities of global urban building data in OpenStreetMap
Authors: Herfort Benjamin , Lautenbach Sven , Porto de Albuquerque João , Anderson Jennings , Zipf Alexander 
Published: July 2023

AbstractOpenStreetMap (OSM) has evolved as a popular dataset for global urban analyses, such as assessing progress towards the Sustainable Development Goals. However, many analyses do not account for the uneven spatial coverage of existing data. We employ a machine-learning model to infer the completeness of OSM building stock data for 13,189 urban agglomerations worldwide. For 1,848 urban centres (16% of the urban population), OSM building footprint data exceeds 80% completeness, but completeness remains lower than 20% for 9,163 cities (48% of the urban population). Although OSM data inequalities have recently receded, partially as a result of humanitarian mapping efforts, a complex unequal pattern of spatial biases remains, which vary across various human development index groups, population sizes and geographic regions. Based on these results, we provide recommendations for data producers and urban analysts to manage the uneven coverage of OSM data, as well as a framework to support the assessment of completeness biases.
Multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function
Authors: Liu Kai , Nilsson Ralf , Lázaro-Ibáñez Elisa , Duàn Hanna , Miliotis Tasso , Strimfors Marie , Lerche Michael , Salgado Ribeiro Ana Rita , Ulander Johan , Lindén Daniel , Salvati Anna , Sabirsh Alan 
Published: July 2023

AbstractIn terms of lipid nanoparticle (LNP) engineering, the relationship between particle composition, delivery efficacy, and the composition of the biocoronas that form around LNPs, is poorly understood. To explore this we analyze naturally efficacious biocorona compositions using an unbiased screening workflow. First, LNPs are complexed with plasma samples, from individual lean or obese male rats, and then functionally evaluated in vitro. Then, a fast, automated, and miniaturized method retrieves the LNPs with intact biocoronas, and multiomics analysis of the LNP-corona complexes reveals the particle corona content arising from each individual plasma sample. We find that the most efficacious LNP-corona complexes were enriched with high-density lipoprotein (HDL) and, compared to the commonly used corona-biomarker Apolipoprotein E, corona HDL content was a superior predictor of in-vivo activity. Using technically challenging and clinically relevant lipid nanoparticles, these methods reveal a previously unreported role for HDL as a source of ApoE and, form a framework for improving LNP therapeutic efficacy by controlling corona composition.
A deep learning approach for morphological feature extraction based on variational auto-encoder: an application to mandible shape
Authors: Tsutsumi Masato , Saito Nen , Koyabu Daisuke , Furusawa Chikara 
Published: July 2023

AbstractShape measurements are crucial for evolutionary and developmental biology; however, they present difficulties in the objective and automatic quantification of arbitrary shapes. Conventional approaches are based on anatomically prominent landmarks, which require manual annotations by experts. Here, we develop a machine-learning approach by presenting morphological regulated variational AutoEncoder (Morpho-VAE), an image-based deep learning framework, to conduct landmark-free shape analysis. The proposed architecture combines the unsupervised and supervised learning models to reduce dimensionality by focusing on morphological features that distinguish data with different labels. We applied the method to primate mandible image data. The extracted morphological features reflected the characteristics of the families to which the organisms belonged, despite the absence of correlation between the extracted morphological features and phylogenetic distance. Furthermore, we demonstrated the reconstruction of missing segments from incomplete images. The proposed method provides a flexible and promising tool for analyzing a wide variety of image data of biological shapes even those with missing segments.
Interstitial-fluid shear stresses induced by vertically oscillating head motion lower blood pressure in hypertensive rats and humans
Authors: Murase Shuhei , Sakitani Naoyoshi , Maekawa Takahiro , Yoshino Daisuke , Takano Kouji , Konno Ayumu , Hirai Hirokazu , Saito Taku , Tanaka Sakae , Shinohara Keisuke , Kishi Takuya , Yoshikawa Yuki , Sakai Takamasa , Ayaori Makoto , Inanami Hirohiko , Tomiyasu Koji , Takashima Atsushi , Ogata Toru , Tsuchimochi Hirotsugu , Sato Shinya , Saito Shigeyoshi , Yoshino Kohzoh , Matsuura Yuiko , Funamoto Kenichi , Ochi Hiroki , Shinohara Masahiro , Nagao Motoshi , Sawada Yasuhiro 
Published: July 2023

AbstractThe mechanisms by which physical exercise benefits brain functions are not fully understood. Here, we show that vertically oscillating head motions mimicking mechanical accelerations experienced during fast walking, light jogging or treadmill running at a moderate velocity reduce the blood pressure of rats and human adults with hypertension. In hypertensive rats, shear stresses of less than 1 Pa resulting from interstitial-fluid flow induced by such passive head motions reduced the expression of the angiotensin II type-1 receptor in astrocytes in the rostral ventrolateral medulla, and the resulting antihypertensive effects were abrogated by hydrogel introduction that inhibited interstitial-fluid movement in the medulla. Our findings suggest that oscillatory mechanical interventions could be used to elicit antihypertensive effects.
Dynamic de novo heterochromatin assembly and disassembly at replication forks ensures fork stability
Authors: Gaggioli Vincent , Lo Calvin S. Y. , Reverón-Gómez Nazaret , Jasencakova Zuzana , Domenech Heura , Nguyen Hong , Sidoli Simone , Tvardovskiy Andrey , Uruci Sidrit , Slotman Johan A. , Chai Yi , Gonçalves João G. S. C. Souto , Manolika Eleni Maria , Jensen Ole N. , Wheeler David , Sridharan Sriram , Chakrabarty Sanjiban , Demmers Jeroen , Kanaar Roland , Groth Anja , Taneja Nitika 
Published: July 2023

AbstractChromatin is dynamically reorganized when DNA replication forks are challenged. However, the process of epigenetic reorganization and its implication for fork stability is poorly understood. Here we discover a checkpoint-regulated cascade of chromatin signalling that activates the histone methyltransferase EHMT2/G9a to catalyse heterochromatin assembly at stressed replication forks. Using biochemical and single molecule chromatin fibre approaches, we show that G9a together with SUV39h1 induces chromatin compaction by accumulating the repressive modifications, H3K9me1/me2/me3, in the vicinity of stressed replication forks. This closed conformation is also favoured by the G9a-dependent exclusion of the H3K9-demethylase JMJD1A/KDM3A, which facilitates heterochromatin disassembly upon fork restart. Untimely heterochromatin disassembly from stressed forks by KDM3A enables PRIMPOL access, triggering single-stranded DNA gap formation and sensitizing cells towards chemotherapeutic drugs. These findings may help in explaining chemotherapy resistance and poor prognosis observed in patients with cancer displaying elevated levels of G9a/H3K9me3.
Class 3 PI3K coactivates the circadian clock to promote rhythmic de novo purine synthesis
Authors: Alkhoury Chantal , Henneman Nathaniel F. , Petrenko Volodymyr , Shibayama Yui , Segaloni Arianna , Gadault Alexis , Nemazanyy Ivan , Le Guillou Edouard , Wolide Amare Desalegn , Antoniadou Konstantina , Tong Xin , Tamaru Teruya , Ozawa Takeaki , Girard Muriel , Hnia Karim , Lutter Dominik , Dibner Charna , Panasyuk Ganna 
Published: July 2023

AbstractMetabolic demands fluctuate rhythmically and rely on coordination between the circadian clock and nutrient-sensing signalling pathways, yet mechanisms of their interaction remain not fully understood. Surprisingly, we find that class 3 phosphatidylinositol-3-kinase (PI3K), known best for its essential role as a lipid kinase in endocytosis and lysosomal degradation by autophagy, has an overlooked nuclear function in gene transcription as a coactivator of the heterodimeric transcription factor and circadian driver Bmal1–Clock. Canonical pro-catabolic functions of class 3 PI3K in trafficking rely on the indispensable complex between the lipid kinase Vps34 and regulatory subunit Vps15. We demonstrate that although both subunits of class 3 PI3K interact with RNA polymerase II and co-localize with active transcription sites, exclusive loss of Vps15 in cells blunts the transcriptional activity of Bmal1–Clock. Thus, we establish non-redundancy between nuclear Vps34 and Vps15, reflected by the persistent nuclear pool of Vps15 in Vps34-depleted cells and the ability of Vps15 to coactivate Bmal1–Clock independently of its complex with Vps34. In physiology we find that Vps15 is required for metabolic rhythmicity in liver and, unexpectedly, it promotes pro-anabolic de novo purine nucleotide synthesis. We show that Vps15 activates the transcription of Ppat, a key enzyme for the production of inosine monophosphate, a central metabolic intermediate for purine synthesis. Finally, we demonstrate that in fasting, which represses clock transcriptional activity, Vps15 levels are decreased on the promoters of Bmal1 targets, Nr1d1 and Ppat. Our findings open avenues for establishing the complexity for nuclear class 3 PI3K signalling for temporal regulation of energy homeostasis.
De novo detection of somatic mutations in high-throughput single-cell profiling data sets
Authors: Muyas Francesc , Sauer Carolin M. , Valle-Inclán Jose Espejo , Li Ruoyan , Rahbari Raheleh , Mitchell Thomas J. , Hormoz Sahand , Cortés-Ciriano Isidro 
Published: July 2023

AbstractCharacterization of somatic mutations at single-cell resolution is essential to study cancer evolution, clonal mosaicism and cell plasticity. Here, we describe SComatic, an algorithm designed for the detection of somatic mutations in single-cell transcriptomic and ATAC-seq (assay for transposase-accessible chromatin sequence) data sets directly without requiring matched bulk or single-cell DNA sequencing data. SComatic distinguishes somatic mutations from polymorphisms, RNA-editing events and artefacts using filters and statistical tests parameterized on non-neoplastic samples. Using >2.6 million single cells from 688 single-cell RNA-seq (scRNA-seq) and single-cell ATAC-seq (scATAC-seq) data sets spanning cancer and non-neoplastic samples, we show that SComatic detects mutations in single cells accurately, even in differentiated cells from polyclonal tissues that are not amenable to mutation detection using existing methods. Validated against matched genome sequencing and scRNA-seq data, SComatic achieves F1 scores between 0.6 and 0.7 across diverse data sets, in comparison to 0.2–0.4 for the second-best performing method. In summary, SComatic permits de novo mutational signature analysis, and the study of clonal heterogeneity and mutational burdens at single-cell resolution.