bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering the distinct transcriptomic and gene regulatory map in adult macaque basal ganglia cells
Authors: Li Zihao , Sun Yunong , Ding Lingjun , Yang Jing , Huang Jinrong , Cheng Mengnan , Wu Liang , Zhuang Zhenkun , Chen Cheng , Huang Yunqi , Zhu Zhiyong , Jiang Siyuan , Huang Fubaoqian , Wang Chunqing , Liu Shiping , Liu Longqi , Lei Ying
Published: December 2023

Background

The basal ganglia are a complex of interconnected subcortical structures located beneath the mammalian cerebral cortex. The degeneration of dopaminergic neurons in the basal ganglia is the primary pathological feature of Parkinson's disease. Due to a lack of integrated analysis of multiomics datasets across multiple basal ganglia brain regions, very little is known about the regulatory mechanisms of this area.

Findings

We utilized high-throughput transcriptomic and epigenomic analysis to profile over 270,000 single-nucleus cells to create a cellular atlas of the basal ganglia, characterizing the cellular composition of 4 regions of basal ganglia in adult macaque brain, including the striatum, substantia nigra (SN), globus pallidum, and amygdala. We found a distinct epigenetic regulation on gene expression of neuronal and nonneuronal cells across regions in basal ganglia. We identified a cluster of SN-specific astrocytes associated with neurodegenerative diseases and further explored the conserved and primate-specific transcriptomics in SN cell types across human, macaque, and mouse. Finally, we integrated our epigenetic landscape of basal ganglia cells with human disease heritability and identified a regulatory module consisting of candidate cis-regulatory elements that are specific to medium spiny neurons and associated with schizophrenia.

Conclusions

In general, our macaque basal ganglia atlas provides valuable insights into the comprehensive transcriptome and epigenome of the most important and populous cell populations in the macaque basal ganglia. We have identified 49 cell types based on transcriptomic profiles and 47 cell types based on epigenomic profiles, some of which exhibit region specificity, and characterized the molecular relationships underlying these brain regions.
DriverMP enables improved identification of cancer driver genes
Authors: Liu Yangyang , Han Jiyun , Kong Tongxin , Xiao Nannan , Mei Qinglin , Liu Juntao
Published: December 2023

Background

Cancer is widely regarded as a complex disease primarily driven by genetic mutations. A critical concern and significant obstacle lies in discerning driver genes amid an extensive array of passenger genes.

Findings

We present a new method termed DriverMP for effectively prioritizing altered genes on a cancer-type level by considering mutated gene pairs. It is designed to first apply nonsilent somatic mutation data, protein‒protein interaction network data, and differential gene expression data to prioritize mutated gene pairs, and then individual mutated genes are prioritized based on prioritized mutated gene pairs. Application of this method in 10 cancer datasets from The Cancer Genome Atlas demonstrated its great improvements over all the compared state-of-the-art methods in identifying known driver genes. Then, a comprehensive analysis demonstrated the reliability of the novel driver genes that are strongly supported by clinical experiments, disease enrichment, or biological pathway analysis.

Conclusions

The new method, DriverMP, which is able to identify driver genes by effectively integrating the advantages of multiple kinds of cancer data, is available at https://github.com/LiuYangyangSDU/DriverMP. In addition, we have developed a novel driver gene database for 10 cancer types and an online service that can be freely accessed without registration for users. The DriverMP method, the database of novel drivers, and the user-friendly online server are expected to contribute to new diagnostic and therapeutic opportunities for cancers.
Multi-omics landscape to decrypt the distinct flavonoid biosynthesis of Scutellaria baicalensis across multiple tissues
Authors: Guo Dandan , Zhu Zhenyu , Wang Zhe , Feng Fei , Cao Qi , Xia Zhewei , Jia Xinlei , Lv Diya , Han Ting , Chen Xiaofei
Published: December 2023

Scutellaria baicalensis Georgi, also known as huang-qin in traditional Chinese medicine, is a widely used herbal remedy due to its anticancer, antivirus, and hepatoprotective properties. The S. baicalensis genome was sequenced many years ago; by contrast, the proteome as the executer of most biological processes of S. baicalensis in the aerial parts, as well as the secondary structure of the roots (xylem, phloem, and periderm), is far less comprehensively characterized. Here we attempt to depict the molecular landscape of the non-model plant S. baicalensis through a multi-omics approach, with the goal of constructing a highly informative and valuable reference dataset. Furthermore, we provide an in-depth characterization dissection to explain the two distinct flavonoid biosynthesis pathways that exist in the aerial parts and root, at the protein and phosphorylated protein levels. Our study provides detailed spatial proteomic and phosphoproteomic information in the context of secondary structures, with implications for the molecular profiling of secondary metabolite biosynthesis in non-model medicinal plants.
Tracking organelle activities through efficient and stable root genetic transformation system in woody plants
Authors: Gong Jinli , Chen Yishan , Xu Yanna , Gu Miaofeng , Ma Haijie , Hu Xiaoli , Li Xiaolong , Jiao Chen , Sun Xuepeng
Published: December 2023

Due to the protracted transgenic timeline and low efficiency in stable genetic transformation of woody plants, there has been limited exploration of real-time organelle imaging within stable transgenic woody plant cells. Here, we established an efficient in vivo genetic transformation system for woody plants using an Agrobacterium rhizogenes-mediated approach. This system was successfully validated in multiple perennial woody species. Using citrus as a model, we introduced organelle-targeted fluorescent reporters via genetic transformation and investigated their subcellular localization and dynamics using advanced imaging techniques, such as confocal microscopy and live-cell imaging. Moreover, we subjected transgenic MT-GFP-labeled mitochondria in root cells to stress conditions simulating agricultural adversities faced by fruit crops. The stress-induced experiments revealed notable alterations in mitochondrial morphology. Our study contributes novel insights into membrane trafficking processes, protein localization dynamics, and cellular physiology in woody plants, while also providing stable and efficient genetic transformation methods for perennial woody species.
An efficient protoplast-based genome editing protocol for Vitis species
Authors: Tricoli David M , Debernardi Juan M
Published: December 2023

CRISPR-Cas technologies allow for precise modifications in plant genomes and promise to revolutionize agriculture. These technologies depend on the delivery of editing components into plant cells and the regeneration of fully edited plants. In vegetatively propagated plants, such as grape, protoplast culture provides one of the best avenues for producing non-chimeric and transgene-free genome-edited plants. However, poor regeneration of plants from protoplasts has hindered their implementation for genome editing. Here, we report an efficient protocol for regenerating plants from protoplasts from multiple grape varieties. By encapsulating the protoplasts in calcium alginate beads and co-culturing them with feeder cultures, the protoplasts divide to form callus colonies that regenerate into embryos and ultimately plants. This protocol worked successfully in wine and table grape (Vitis vinifera) varieties, as well as grape rootstocks and the grapevine wild relative Vitis arizonica. Moreover, by transfecting protoplasts with CRISPR-plasmid or ribonucleoprotein (RNP) complexes, we regenerated albino plants with edits in VvPHYTOENE DESATURASE gene in three varieties and in V. arizonica. The results reveal the potential of this platform to facilitate genome editing in Vitis species.
The Interrelationship between EFL Learning Motivation and Dictionary Use
Authors: Fajt Balázs , Bánhegyi Mátyás , Márkus Katalin P
Published: December 2023

Using dictionaries has been seen as an important aspect of L2 learning at all levels of L2 proficiency. Yet, in many cases dictionary use seems a considerably neglected part of L2 teaching. There is no doubt, however, that L2 learners should be encouraged to use dictionaries independently and autonomously, as they will be unable to rely on language teachers or other proficient L2 speakers to assist them throughout their whole lives. Using Dörnyei’s (2005) L2 Motivational Self System (L2MSS) framework, this quantitative study (N=925) investigates the interrelationship between L2 learning motivation, willingness to pay for dictionaries, reading dictionaries’ usage guides and willingness to use dictionaries. The accumulated data were analysed through structural equation modelling (SEM). Even though not necessarily generalisable to other contexts, the results show that EFL learning motivation has an impact on willingness to buy dictionaries and willingness to use dictionaries. Our data reveal that in the L2MSS, two components (motivated language learning behaviour and the ideal L2 self) have an impact on attitudes to dictionary use.
Greenness Assessment and Validation of HPLC Method for Simultaneous Determination of Resveratrol and Vitamin E in Dietary Supplements
Authors: Topkoska Marina , Miloshevska Martina , Piponski Marjan , Slaveska Spirevska Irena , Nakov Natalija , Brezovska Katerina , Acevska Jelena
Published: December 2023

Background

There is an increasing interest in the use of a combination of trans-resveratrol and vitamin E in dietary supplements. Determination of the content of both components is essential for confirmation of the quality of the product.

Objective

To establish the applicability and ensure the greenness of the previously developed high-throughput HPLC/UV method for the simultaneous determination of trans-resveratrol and alpha-tocopherol acetate (vitamin E) in dietary supplements.

Method

Separation was performed on RP C8 Select B chromatographic column, using acetonitrile and water in the mobile phase, with gradient elution. Full method validation was performed in accordance with ICH Q2(R1). The greenness of the method was assessed using the analytical eco-scale (AES) methodology and the analytical greenness metric (AGREE).

Results

The method is selective, linear, precise, and accurate over defined concentration ranges (185–369 µg/mL of trans-resveratrol and 37–75 µg/mL of alpha-tocopherol acetate), and it has a suitable sensitivity (limits of detection and quantification are 7.7 and 23.3 µg/mL for resveratrol and 2.6 and 7.8 µg/mL for tocopherol acetate, respectively). The obtained analytical eco-scale score of 77 and the pale green AGREE pictogram with an overall score of 0.61 confirm the method’s greenness.

Conclusions

The sensitivity and selectivity of the method, its short analysis time (7 min), the low negative environmental impact, and the simple sample preparation make the method readily applicable to inline quality control procedures.

Highlights

A method for simultaneously analyzing vitamin E and resveratrol in dietary supplements is presented. The method is rapid, includes a simple sample preparation procedure, and has a low environmental impact.
VMAT with DIBH in hypofractionated radiotherapy for left-sided breast cancer after breast-conserving surgery: results of a non-inferiority clinical study
Authors: Jingu Keiichi , Ito Kengo , Sato Kiyokazu , Umezawa Rei , Yamamoto Takaya , Takahashi Noriyoshi , Suzuki Yu , Kishida Keita , Omata So , Harada Hinako , Seki Yasuhiro , Chiba Nanae , Kadoya Noriyuki
Published: December 2023

The purpose of this study was to show the safety of volumetric modulated arc therapy (VMAT) with deep inspiration breath-hold (DIBH) in hypofractionated radiotherapy for left-sided breast cancer after breast-conserving surgery in a clinical setting. Twenty-five Japanese women, aged 20–59 years, who were enrolled in this prospective non-inferiority study received VMAT under the condition of DIBH with 42.4 Gy/16 fractions for whole-breast irradiation (WBI) ± boost irradiation for the tumor bed to show the non-inferiority of VMAT with DIBH to conventional fractionated WBI with free breathing. The primary endpoint was the rate of occurrence of radiation dermatitis of Grade 3 or higher or pneumonitis of Grade 2 or higher within 6 months after the start of radiotherapy. This study was registered with UMIN00004321. All of the enrolled patients completed the planned radiotherapy without interruption. The evaluation of adverse events showed that three patients (12.0%) had Grade 2 radiation dermatitis. There was no other Grade 2 adverse event and there was no patient with an adverse event of Grade 3 or higher. Those results confirmed our hypothesis that the experimental treatment method is non-inferior compared with our historical results. There was no patient with locoregional recurrence or metastases. In conclusion, VMAT under the condition of DIBH in hypofractionated radiotherapy for left-sided breast cancer after breast-conserving surgery can be performed safely in a clinical setting.
Modelling JWST mid-infrared counts: excellent consistency with models derived for IRAS, ISO, and Spitzer
Authors: Rowan-Robinson Michael
Published: December 2023

Models derived in 2009 to fit mid-infrared (8–24 micron) source counts from the IRAS, ISO, and Spitzer missions, provide an excellent fit to deep counts with JWST, demonstrating that the evolution of dusty star-forming galaxies is well understood. The evolution of dust in galaxies at high redshifts is discussed and a simple prescription is proposed to model this. This allows more realistic models for source-counts at submillimetre wavelength. A reasonable fit to 250, 500, 850, and 1100 micron counts is obtained. This paper therefore draws together the IRAS, ISO, Spitzer, Akari, Herschel, submillimetre ground-based, and JWST surveys into a single picture.
Ursa: A Comprehensive Multiomics Toolbox for High-Throughput Single-Cell Analysis
Authors: Pan Lu , Mou Tian , Huang Yue , Hong Weifeng , Yu Min , Li Xuexin
Published: December 2023

The burgeoning amount of single-cell data has been accompanied by revolutionary changes to computational methods to map, quantify, and analyze the outputs of these cutting-edge technologies. Many are still unable to reap the benefits of these advancements due to the lack of bioinformatics expertise. To address this issue, we present Ursa, an automated single-cell multiomics R package containing 6 automated single-cell omics and spatial transcriptomics workflows. Ursa allows scientists to carry out post-quantification single or multiomics analyses in genomics, transcriptomics, epigenetics, proteomics, and immunomics at the single-cell level. It serves as a 1-stop analytic solution by providing users with outcomes to quality control assessments, multidimensional analyses such as dimension reduction and clustering, and extended analyses such as pseudotime trajectory and gene-set enrichment analyses. Ursa aims bridge the gap between those with bioinformatics expertise and those without by providing an easy-to-use bioinformatics package for scientists in hoping to accelerate their research potential. Ursa is freely available at https://github.com/singlecellomics/ursa.
Cryptotis nigrescens (Eulipotyphla: Soricidae)
Authors: Woodman Neal , Timm Robert M
Published: December 2023

The blackish small-eared shrew, Cryptotis nigrescens (Allen, 1895), is a blarinine soricid that occurs in high-elevation premontane wet forest and cloud forest in the Central American countries of Costa Rica and Panama. The species is taxonomically monotypic, although it exhibits size variation that manifests as a gradual increase in size from northwest to southeast. Habitat loss is currently the greatest threat to the species’ existence, although populations in the few areas where C. nigrescens has been studied appear to be healthy, and the International Union for Conservation of Nature (IUCN) classifies it as a species whose conservation status is “Least Concern” (LC). We include a complete synonymy for the genus Cryptotis Pomel, 1848.
A Bayesian noisy logic model for inference of transcription factor activity from single cell and bulk transcriptomic data
Authors: Arriojas Argenis , Patalano Susan , Macoska Jill , Zarringhalam Kourosh
Published: December 2023

The advent of high-throughput sequencing has made it possible to measure the expression of genes at relatively low cost. However, direct measurement of regulatory mechanisms, such as transcription factor (TF) activity is still not readily feasible in a high-throughput manner. Consequently, there is a need for computational approaches that can reliably estimate regulator activity from observable gene expression data. In this work, we present a noisy Boolean logic Bayesian model for TF activity inference from differential gene expression data and causal graphs. Our approach provides a flexible framework to incorporate biologically motivated TF–gene regulation logic models. Using simulations and controlled over-expression experiments in cell cultures, we demonstrate that our method can accurately identify TF activity. Moreover, we apply our method to bulk and single cell transcriptomics measurements to investigate transcriptional regulation of fibroblast phenotypic plasticity. Finally, to facilitate usage, we provide user-friendly software packages and a web-interface to query TF activity from user input differential gene expression data: https://umbibio.math.umb.edu/nlbayes/.
Sizes of Countable Sets
Authors: Trlifajová Kateřina
Published: December 2023

The paper introduces the notion of size of countable sets, which preserves the Part-Whole Principle. The sizes of the natural and the rational numbers, their subsets, unions, and Cartesian products are algorithmically enumerable as sequences of natural numbers. The method is similar to that of Numerosity Theory, but in comparison it is motivated by Bolzano’s concept of infinite series, it is constructive because it does not use ultrafilters, and set sizes are uniquely determined. The results mostly agree, but some differ, such as the size of rational numbers. However, set sizes are only partially, not linearly, ordered. Quid pro quo.
Relativistic Faddeev 3D equations for three-body bound states without two-body t-matrices
Authors: Mohammadzadeh M , Radin M , Hadizadeh M R
Published: December 2023

This paper explores a novel revision of the Faddeev equation for three-body (3B) bound states, as initially proposed in Ref. [J. Golak, K. Topolnicki, R. Skibiński, W. Glöckle, H. Kamada, A. Nogga, Few Body Syst. 54, 2427 (2013)]. This innovative approach, referred to as t-matrix-free in this paper, directly incorporates two-body (2B) interactions and completely avoids the 2B transition matrices. We extend this formalism to relativistic 3B bound states using a three-dimensional (3D) approach without using partial wave decomposition. To validate the proposed formulation, we perform a numerical study using spin-independent Malfliet–Tjon and Yamaguchi interactions. Our results demonstrate that the relativistic t-matrix-free Faddeev equation, which directly implements boosted interactions, accurately reproduces the 3B mass eigenvalues obtained from the conventional form of the Faddeev equation, referred to as t-matrix-dependent in this paper, with boosted 2B t-matrices. Moreover, the proposed formulation provides a simpler alternative to the standard approach, avoiding the computational complexity of calculating boosted 2B t-matrices and leading to significant computational time savings.
Comparative role of acetaminophen, carbon tetrachloride and thioacetamide in development of fibrosis in rats
Authors: Singh Shubham , Nirala Satendra Kumar , Bhadauria Monika
Published: December 2023

Background

Several hepatotoxicants such as acetaminophen, carbon tetrachloride, and thioacetamide are repeatedly used to develop hepatic fibrosis to mimic the histological and hemodynamic characteristics of human illness. It may be a good idea to establish a better model among these hepatotoxicants to develop hepatic fibrosis.

Aim

The present study evaluated comparative toxic effects of three model hepatotoxicants for experimental progression of fibrosis or cirrhosis.

Materials and methods

Acetaminophen (200 mg/kg), carbon tetrachloride (200 µl/kg) and thioacetamide (200 mg/kg) were administered orally, thrice in a week for 8 weeks in different groups. After 8 weeks of exposure, animals were euthanized, blood and tissues were collected for various hematological, serological, tissue biochemical analysis and histological observations for comparative assessment of toxic consequences.

Results

Significant deviation was noted in liver function tests, lipid peroxidation, glutathione, activities of superoxide dismutase, catalase, and GSH cycle enzymes; aniline hydroxylase, amidopyrine-N-demethylase, DNA fragmentation and level of hydroxyproline when compared with control group. Histology also depicted damage in liver histoarchitecture with exposure to acetaminophen, carbon tetrachloride and thioacetamide. Tukey’s HSD post hoc test confirmed that thioacetamide produced severe toxic effects in comparison to carbon tetrachloride and acetaminophen.

Conclusion

In conclusion, toxic effects were noted in ascending order as acetaminophen.
Evaluation of a computational model for mycetoma-causative agents identification
Authors: Omar Ali Hyam , Abraham Romain , Desoubeaux Guillaume , Fahal Ahmed H , Tauber Clovis
Published: December 2023

Background

The therapeutic strategy for mycetoma relies heavily on the identification of the causative agents, which are either fungal or bacterial. While histopathological examination of surgical biopsies is currently the most used diagnostic tool, it requires well-trained pathologists, who are lacking in most rural areas where mycetoma is endemic. In this work we propose and evaluate a machine learning approach that semi-automatically analyses histopathological microscopic images of grains and provides a classification of the disease as eumycetoma or actinomycetoma.

Methods

The computational model is based on radiomics and partial least squares. It is assessed on a dataset that includes 890 individual grains collected from 168 patients originating from the Mycetoma Research Centre in Sudan. The dataset contained 94 eumycetoma cases and 74 actinomycetoma cases, with a distribution of the species among the two causative agents that is representative of the Sudanese distribution.

Results

The proposed model achieved identification of causative agents with an accuracy of 91.89%, which is comparable to the accuracy of experts from the domain. The method was found to be robust to a small error in the segmentation of the grain and to changes in the acquisition protocol. Among the radiomics features, the homogeneity of mycetoma grain textures was found to be the most discriminative feature for causative agent identification.

Conclusion

The results presented in this study support that this computational approach could greatly benefit rural areas with limited access to specialized clinical centres and also provide a second opinion for expert pathologists to implement the appropriate therapeutic strategy.
BCAS2 regulates oocyte meiotic prophase I by participating in mRNA alternative splicing
Authors: Yao Xiaohong , Wang Chaofan , Yu Weiran , Sun Longjie , Lv Zheng , Xie Xiaomei , Tian Shuang , Yan Lu , Li Lei , Liu Jiali
Published: December 2023

Oocyte meiotic prophase I (MI) is an important event in female reproduction. Breast cancer amplified sequence 2 (BCAS2) is a component of the spliceosome. Previous reports have shown that BCAS2 is critical in male germ cell meiosis, oocyte development, and early embryo genome integrity. However, the role of BCAS2 in oocyte meiosis has not been reported. We used Stra8‐GFPCre mice to knock out Bcas2 in oocytes during the pachytene phase. The results of fertility tests showed that Bcas2 conditional knockout (cKO) in oocytes results in infertility in female mice. Morphological analysis showed that the number of primordial follicles in the ovaries of 2‐month‐old (M) mice was significantly reduced and that follicle development was blocked. Further analysis showed that the number of primordial follicles decreased and that follicle development was slowed in 7‐day postpartum (dpp) ovaries. Moreover, primordial follicles undergo apoptosis, and DNA damage cannot be repaired in primary follicle oocytes. Meiosis was abnormal; some oocytes could not reach the diplotene stage, and more oocytes could not develop to the dictyotene stage. Alternative splicing (AS) analysis revealed abnormal AS of deleted in azoospermia like (Dazl) and diaphanous related formin 2 (Diaph2) oogenesis‐related genes in cKO mouse ovaries, and the process of AS was involved by CDC5L and PRP19.
Single‐cell sequencing of head and neck carcinoma: Transcriptional landscape and prognostic model based on malignant epithelial cell features
Authors: Xiong Ming , Hu Juan‐Juan , Yao Meng‐Lin , Song Ting‐Ting , Zhao Lei , Mou Bi‐Qin , Qian Ying‐Xue , Zheng Mei‐Jun , Dong Yi‐Jun , Wang Hai‐Yang , Zou Jian , Yang Hui
Published: December 2023

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the development of novel therapeutic strategies for HNSCC requires a profound understanding of tumor cells and the tumor microenvironment (TME). Additionally, HNSCC has a poor prognosis, necessitating the use of genetic markers for predicting clinical outcomes in HNSCC. In this study, we performed single‐cell sequencing analysis on tumor tissues from seven HNSCC patients, along with one adjacent normal tissue. Firstly, the analysis of epithelial cell clusters revealed two clusters of malignant epithelial cells, characterized by unique gene expression patterns and dysregulated signaling pathways compared to normal epithelial cells. Secondly, the examination of the TME unveiled extensive crosstalk between fibroblasts and malignant epithelial cells, potentially mediated through ligand‐receptor interactions such as COL1A1‐SDC1, COL1A1‐CD44, and COL1A2‐SDC1. Furthermore, transcriptional heterogeneity was observed in immune cells present in the TME, including macrophages and dendritic cells. Finally, leveraging the gene expression profiles of malignant epithelial cells, we developed a prognostic model comprising six genes, which we validated using two independent datasets. These findings shed light on the heterogeneity within HNSCC tumors and the intricate interplay between malignant cells and the TME. Importantly, the developed prognostic model demonstrates high efficacy in predicting the survival outcomes of HNSCC patients.
Fusobacterium nucleatum exacerbates the progression of pulpitis by regulating the STING‐dependent pathway
Authors: Zhou Lu , Mao Han‐Qing , Li Jia‐Qi , Chen Zhi , Zhang Lu
Published: December 2023

Bacterial infection is the main cause of pulpitis. However, whether a dominant bacteria can promote the progression of pulpitis and its underlying mechanism remains unclear. We provided a comprehensive assessment of the microbiota alteration in pulpitis using 16S rRNA sequencing. Fusobacterium nucleatum was the most enriched in pulpitis and played a pathogenic role accelerating pulpitis progression in rat pulpitis model. After odontoblast‐like cells cocultured with F. nucleatum, the stimulator of interferon genes (STING) pathway and autophagy were activation. There was a float of STING expression during F. nucleatum stimulation. STING was degraded by autophagy at the early stage. At the late stage, F. nucleatum stimulated mitochondrial Reactive Oxygen Species (ROS) production, mitochondrial dysfunction and then mtDNA escape into cytosol. mtDNA, which escaped into cytosol, caused more cytosolic mtDNA binds to cyclic GMP‐AMP synthase (cGAS). The release of IFN‐β was dramatically reduced when mtDNA‐cGAS‐STING pathway inhibited. STING−/− mice showed milder periapical bone loss and lower serum IFN‐β levels compared with wildtype mice after 28 days F. nucleatum‐infected pulpitis model establishment. Our data demonstrated that F. nucleatum exacerbated the progression of pulpitis, which was mediated by the STING‐dependent pathway.
An Initial Investigation of Diaphragm Neurostimulation in Patients with Acute Respiratory Distress Syndrome
Authors: Parfait Mélodie , Rohrs Elizabeth , Joussellin Vincent , Mayaux Julien , Decavèle Maxens , Reynolds Steven , Similowski Thomas , Demoule Alexandre , Dres Martin
Published: December 2023

Background

Lung protective ventilation aims at limiting lung stress and strain. By reducing the amount of pressure transmitted by the ventilator into the lungs, diaphragm neurostimulation offers a promising approach to minimize ventilator-induced lung injury. This study investigates the physiologic effects of diaphragm neurostimulation in acute respiratory distress syndrome (ARDS) patients. The hypothesis was that diaphragm neurostimulation would improve oxygenation, would limit the distending pressures of the lungs, and would improve cardiac output.

Methods

Patients with moderate ARDS were included after 48 h of invasive mechanical ventilation and had a left subclavian catheter placed to deliver bilateral transvenous phrenic nerve stimulation. Two 60-min volume-controlled mechanical ventilation (control) sessions were interspersed by two 60-min diaphragm neurostimulation sessions delivered continually, in synchrony with the ventilator. Gas exchange, lung mechanics, chest electrical impedance tomography, and cardiac index were continuously monitored and compared across four sessions. The primary endpoint was the Pao2
/fraction of inspired oxygen (Fio
2) ratio at the end of each session, and the secondary endpoints were lung mechanics and hemodynamics.

Results

Thirteen patients were enrolled but the catheter could not be inserted in one, leaving 12 patients for analysis. All sessions were conducted without interruption and well tolerated. The Pao2
/Fio
2 ratio did not change during the four sessions. Median (interquartile range) plateau pressure was 23 (20 to 31) cm H2O and 21 (17 to 25) cm H2O, driving pressure was 14 (12 to 18) cm H2O and 11 (10 to 13) cm H2O, and end-inspiratory transpulmonary pressure was 9 (5 to 11) cm H2O and 7 (4 to 11) cm H2O during mechanical ventilation alone and during mechanical ventilation + neurostimulation session, respectively. The dorsal/ventral ventilation surface ratio was 0.70 (0.54 to 0.91) when on mechanical ventilation and 1.20 (0.76 to 1.33) during the mechanical ventilation + neurostimulation session. The cardiac index was 2.7 (2.3 to 3.5) l · min–1 · m–2 on mechanical ventilation and 3.0 (2.4 to 3.9) l · min–1 · m–2 on mechanical ventilation + neurostimulation.

Conclusions

This proof-of-concept study showed the feasibility of short-term diaphragm neurostimulation in conjunction with mechanical ventilation in ARDS patients. Diaphragm neurostimulation was associated with positive effects on lung mechanics and on hemodynamics.

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Improvement in Cellulite Appearance After a Single Treatment Visit With Acoustic Subcision: Long-Term Findings From a Multicenter Clinical Trial
Authors: Tanzi Elizabeth , Capelli Christopher C. , Robertson David , LaTowsky Brenda , Balcom-Luker Shenavia , Jacob Carolyn , Ibrahim Omer , Kaminer Michael S.
Published: December 2023

BACKGROUND

Cellulite is an aesthetically displeasing rippling or dimpling of the skin, primarily on the buttocks/thighs. A recent study showed a novel acoustic subcision device produced significant short-term (12-week) improvement in the appearance of cellulite after a single rapid acoustic pulse (RAP) treatment.

OBJECTIVE

To evaluate the long-term (>52-weeks) efficacy and safety of RAP treatment for improvement in the appearance of cellulite.

MATERIALS AND METHODS

In this prospective, multicenter trial, female participants (n = 42) with severe cellulite were treated with the acoustic subcision device in a single visit. At >52 weeks, blinded board-certified dermatologists assessed efficacy by correctly identifying post-treatment photographs and using a 6-point simplified Cellulite Severity Scale (CSS). Participant satisfaction was also collected. Safety was assessed throughout.

RESULTS

The blinded panel correctly identified post-treatment photographs at a rate of 95.2%; 70.4% of participants had a >1-point reduction in the CSS score from baseline (mean reduction of 1.09). All participants (100%) reported improved cellulite appearance. Overall pain during treatment was rated as 2.4 and 0.3 post-treatment (pain scale 0–10). No device or treatment-related adverse events were reported at the >52-week follow-up.

CONCLUSION

Rapid acoustic pulse treatment significantly improved the long-term appearance of cellulite and was well-tolerated.
Effects of Ultrasound-guided Lower Abdominal Lymphaticovenous Anastomosis on Lower Abdominal Lymphedema
Authors: Hara Hisako , Mihara Makoto
Published: December 2023

Lymphedema of the lower extremities can be further complicated by lymphedema of the lower abdomen and genitalia. This study aimed to clarify the effect of lower abdominal lymphaticovenous anastomosis (LVA) on lower abdominal lymphedema. The patient was a 61-year-old woman. At the age of 49 years, she underwent treatment for ovarian cancer, including pelvic lymphadenectomy, and she developed lymphedema in the lower abdomen and bilateral thigh 2 years later. During lymphoscintigraphy, isotopes injected into the dorsum of the bilateral feet accumulated in the corresponding areas, indicating that lymph flowed into these areas from the legs. Compression therapy was performed with a girdle; however, its effect was limited. According to the lymphoscintigraphic findings, we performed LVA in the bilateral thighs (two anastomoses each), and the edema symptoms slightly improved postoperatively. However, as edema was still present and the patient sought further relief, we evaluated the lymphatic vessels in the lower abdomen using lymphatic ultrasound and found dilated lymphatic vessels. We performed another LVA in the lower abdomen 1 year after the first LVA (two anastomoses in the right abdomen, one anastomosis in the left abdomen, and an additional anastomosis in the bilateral thighs). The patient’s subjective symptoms improved, and ultrasonography showed a reduction in abdominal lymphedema at 7 months follow-up. For lymphedema in the lower abdomen and genital area that does not improve with compression therapy, appropriate examination to evaluate lymphatic flow and lymphatic degeneration is necessary, and LVA in the lower abdomen may be effective.
The Modern Integrated Plastic Surgery Applicant Pays 150% More Than Their Counterparts Four Years Ago
Authors: Singh Nikhi P. , Kovac Stefan , Boyd Carter J. , King Timothy W.
Published: December 2023

Background:

Integrated plastic surgery residency positions are among the most difficult to obtain. We examine trends in the number of applicants, applications per applicant, and cost over the past five match cycles.

Methods:

In total, 2166 applicants to integrated plastic surgery programs were included. The American Association of Medical Colleges and Electronic Residency Application Service databases were examined to determine applicant trends for the years 2017 to 2021.

Results:

In 2017, there were 564 applicants for integrated plastic surgery residency positions, and in 2021, there were 416 (26% decrease). Across this same time period, the number of applications per applicant nearly doubled (97%) from 30 in 2017 to 59 in 2021, resulting in a 45% increase in the total number of applications. The largest increase in applications per applicant was seen between 2018 and 2019, a 70% increase. From 2017 to 2021, a 10% increase in the number of female applicants and a 43% decrease in the number of male applicants was observed. Cost of applications per applicant increased by 146%, from $514 in 2017 to $1265 in 2021. Total application costs in 2021 were $526,323, an 81% increase from 2017. The future value of these expenditures equals an economic burden of $801,855, assuming a 10-year term student loan at a conservative 4.3% interest rate.

Conclusions:

Despite substantial decreases in the number of applicants, the number of applications and resulting cost of applications have increased by large margins since 2017. This is representative of the increasingly competitive plastic surgery application process.
Effects of trientine and penicillamine on intestinal copper uptake: A mechanistic 64Cu PET/CT study in healthy humans
Authors: Kirk Frederik Teicher , Munk Ditte Emilie , Swenson Eugene Scott , Quicquaro Adam Michael , Vendelbo Mikkel Holm , Schilsky Michael L. , Ott Peter , Sandahl Thomas Damgaard
Published: December 2023

Background and Aims:

Trientine (TRI) and D-penicillamine (PEN) are used to treat copper overload in Wilson disease. Their main mode of action is thought to be through the facilitation of urinary copper excretion. In a recent study, TRI was noninferior to PEN despite lower 24-hour urinary copper excretion than PEN. We tested whether TRI and/or PEN also inhibit intestinal copper absorption.

Approach and Results:

Sixteen healthy volunteers were examined with positron emission tomography (PET)/CT 1 and 15 hours after an oral Copper-64 (64Cu) dose. They then received 7 days of either PEN or TRI (trientine tetrahydrochloride), after which the 64Cu PET/CT scans were repeated. Venous blood samples were also collected. Pretreatment to posttreatment changes of the hepatic 64Cu uptake reflect the effect of drugs on intestinal absorption. 64Cu activity was normalized to dose and body weight and expressed as the mean standard uptake value. TRI (n=8) reduced hepatic 64Cu activity 1 hour after 64Cu dose from 6.17 (4.73) to 1.47 (2.97) standard uptake value, p<0.02, and after 15 hours from 14.24 (3.09) to 6.19 (3.43), p<0.02, indicating strong inhibition of intestinal 64Cu absorption. PEN (n=8) slightly reduced hepatic standard uptake value at 15 hours, from 16.30 (5.63) to 12.17 (1.44), p<0.04.

Conclusions:

In this mechanistic study, we show that TRI inhibits intestinal copper absorption, in addition to its cupriuretic effect. In contrast, PEN has modest effects on the intestinal copper absorption. This may explain why TRI and PEN are equally effective although urinary copper excretion is lower with TRI. The study questions whether the same therapeutic targets for 24-hour urinary excretion apply to both drugs.
Reversal of arterial stiffness in medically and surgically treated unilateral primary aldosteronism
Authors: Chen Zheng-Wei , Liao Che-Wei , Pan Chien-Ting , Tsai Cheng-Hsuan , Chang Yi-Yao , Chang Chin-Chen , Lee Bo-Ching , Chiu Yu-Wei , Huang Wei-Chieh , Lai Tai-Shuan , Lu Ching-Chu , Chueh Jeff S. , Wu Vin-Cent , Hung Chi-Sheng , Lin Yen-Hung ,   the TAIPAI Study Group
Published: December 2023

Objective:

Hyperaldosteronism has adverse effects on cardiovascular structure and function. Laparoscopic adrenalectomy is the gold standard for patients with unilateral primary aldosteronism. For unilateral primary aldosteronism patients unable or unwilling to undergo surgery, the effects of mineralocorticoid receptor antagonists (MRAs) on the reversibility of arterial stiffness and other clinical data remain unclear. We aimed to compare the reversibility of arterial stiffness using pulse wave velocity (PWV) and other clinical parameters between surgically and medically treated unilateral primary aldosteronism patients.

Methods:

We prospectively enrolled 306 unilateral primary aldosteronism patients, of whom 247 received adrenalectomy and 59 received medical treatment with MRAs. Detailed medical history, basic biochemistry and PWV data were collected in both groups before treatment and 1 year after treatment. After propensity score matching (PSM) for age, sex, SBP and DBPs, 149 patients receiving adrenalectomy and 54 patients receiving MRAs were included for further analysis.

Results:

After PSM, the patients receiving adrenalectomy had a greater reduction in blood pressure, increase in serum potassium, and change in PWV (ΔPWV, −53 ± 113 vs. −10 ± 140 cm/s, P = 0.028) than those receiving MRAs 1 year after treatment. Multivariable regression analysis further identified that surgery (compared with MRA treatment), baseline PWV, baseline DBP, the change in DBP and the use of diuretics were independently correlated with ΔPWV.

Conclusion:

Adrenalectomy is superior to MRA treatment with regards to vascular remodeling when treating unilateral primary aldosteronism patients.
Rapid Gastric emptying in spontaneously hypertensive rats
Authors: Salman Umber A. , Schwartz Joyce G. , McMahan Alex C. , Michalek Joel E. , Phillips William T.
Published: December 2023

Objective:

To assess the rate of gastric emptying in spontaneously hypertensive rats (SHR) and to evaluate rapid gastric emptying as a possible predisposing factor for hypertension. Rapid gastric emptying of carbohydrates, known to elevate postprandial serum glucose, has been reported to occur in many insulin-resistant states, including hypertension. SHR exhibit insulin resistance similar to human hypertensive patients. No prior studies have assessed gastric emptying of an oral glucose solution in SHR as compared with control Wistar Kyoto rats (WKY).

Methods:

Using scintigraphic imaging, gastric emptying of a physiologic, orally consumed glucose solution was assessed in 12 SHR and 12 control WKY at 5 weeks of age, prior to the development of hypertension, and at 12 weeks of age after hypertension was fully established.

Results:

At 5 weeks, the gastric half-emptying time (GHET) was 67.8 ± 9.8 min for the SHR vs. 109.3 ± 18 (P = 0.042) minutes for the WKY controls. At 12 weeks, the GHET was 37.29 ± 10.3 min for the SHR vs. 138.53 ± 37.6 (P = 0.016) min for the WKY controls.

Conclusion:

Gastric emptying was significantly more rapid in the SHR before and after the development of hypertension. Even though SHR are known to have increased sympathetic activity associated with their development of hypertension, this increased sympathetic activity does not inhibit gastric emptying. SHR are a promising animal model for investigating therapeutic agents for treating hypertension aimed at slowing the rate of gastric emptying.
DELAYED CLOSURE OF A FULL-THICKNESS MACULAR HOLE AFTER PARS PLANA VITRECTOMY WITH INTERNAL LIMITING MEMBRANE FLAP
Authors: Ahmed Shahanaz B. , Shaikh Sufiyan , Ho Jason
Published: December 2023

Background/Purpose:

The aim of this study is to describe a patient with delayed closure of a stage 3 full-thickness macular hole after pars plana vitrectomy.

Methods:

This is a retrospective case report. Details of the case were obtained from the electronic patient record system, Medisoft.

Results:

A 65-year-old man was referred with a left stage 3 full-thickness macular hole measuring 720 μm and visual acuity of 6/36. He underwent phacovitrectomy, internal limiting membrane peel with an inverted internal limiting membrane flap, and C3F8 gas tamponade. Seven weeks after surgery, the macular hole was smaller at 196 μm but remained open. The patient was listed for repeat surgery; however, another 13 weeks later, the full-thickness macular hole demonstrated type 2 closure without further intervention.

Conclusion:

Delayed macular hole closure after pars plana vitrectomy is rare. In cases where there has been a substantial decrease in the size of a full-thickness macular hole after surgery without full closure, a short period of observation to allow for further closure may be appropriate before reconsidering surgery.
A CASE OF HYPERTENSIVE UVEITIS WITH INTRAVITREAL FARICIMAB
Authors: Kitson Samantha , McAllister Andrew
Published: December 2023

Purpose:

The aim of this study was to report a novel case of hypertensive uveitis with intravitreal faricimab.

Methods:

This is a case report. A 69-year-old woman undergoing treatment of bilateral diabetic macular edema with intravitreal faricimab presented for routine review. Ophthalmic examination was performed including VA, intraocular pressure, gonioscopy, and slitlamp examination. Findings consistent with hypertensive uveitis prompted further infectious/inflammatory/infiltrative uveitis screen.

Results:

The patient developed hypertensive uveitis in the left eye (four weeks after the third injection) with an intraocular pressure of 42 mmHg. Slitlamp examination revealed fine keratic precipitates and mild anterior uveitis. Anterior chamber angle was open on gonioscopy, and there was no vitritis or vasculitis. At the review a week later, the patient had developed hypertensive uveitis in the right eye (six weeks after the fourth injection) with intraocular pressure of 35 mmHg. Slitlamp examination revealed fine keratic precipitates, open angles, and mild vitritis. There was no vasculitis. At both presentations, the patient had preserved VA with no significant visual symptoms. The hypertensive uveitis resolved in both eyes with a course of steroid and antihypertensive eye drops. The uveitis screen was negative apart from elevated urine protein (negative beta-2 microglobulin), which could be explained by known diabetes and hypertension.

Conclusion:

Hypertensive uveitis is a potential adverse reaction to intravitreal faricimab. This case highlights the importance of monitoring intraocular pressure in patients undergoing treatment with faricimab and emphasizes the need for reporting other cases in the community.
What do health care professionals, students, and laypeople in Greece believe about informed consent for research on medical practices? Unleashing Pandora's box
Authors: Giannouli Vaitsa
Published: December 2023

Background:

Attitudes toward informed consent for research on medical practices has been little investigated in Greece in the general population as well as in health care students and professionals, and at the same time, undergraduate and postgraduate curricula with focus on informed consent issues are entirely missing.

Methods:

To explore attitudes toward informed consent for research on medical practices among students, doctors, and laypeople in Greece across several demographic variables. A total of 380 participants (180 first-year healthcare university students from various faculties including medicine, pharmacy, biology, nursing, physiotherapy, midwifery, health care engineers, 100 medical doctors of various specialties working in hospitals and private practice, and 100 laypeople) completed a survey questionnaire along with a detailed demographics questionnaire.

Results:

The results revealed that between the three groups, there were statistically significant differences in the responses for all aspects of attitudes toward informed consent. Overall, Greek participants reported more negative attitudes when compared with findings from the United States. In addition, most of the participants reported lack of educational experience regarding informed consent.

Conclusion:

The findings showed that the efforts and relevant initiatives by the Greek State, private institutions, and the Greek Medical Societies should refocus and emphasize on educational programs concerning the dissemination of relevant scientific information on informed consent processes, either as a provider or as a consumer. Future research should further investigate in more depth the complex influence of additional social and/or psychological factors for the reported differences.