bluuebunny/crossref_metadata_2025_split huggingface dataset:
IncobotulinumtoxinA for Aesthetic Treatments: Review and Recommendations From Latin America
Authors: de Sanctis Pecora Carla , Trindade de Almeida Ada , Figueredo Vinicius , Hirano Cyro , Bugallo Alejandra , Cortés Cristina , Welsh Esperanza C. , Spada Julieta , Heredia Nicolás , de La Fuente Victoria , Muniz Mariana 
Published: August 2024

BACKGROUND
As new aesthetic treatment techniques are developed, the understanding of botulinum toxin type A safety and treatment outcomes continues to evolve.

OBJECTIVE
This article was developed to provide a comprehensive up-to-date reference for clinicians using incobotulinumtoxinA (INCO; Xeomin/Bocouture, Merz Pharmaceuticals GmbH, Frankfurt, Germany) for aesthetic treatments.

PATIENTS AND METHODS/MATERIALS
A Latin American panel of 11 physicians was assembled to discuss and develop recommendations on the use of INCO for aesthetic treatment based on the literature review and their private medical practice.

RESULTS
The panel found that INCO is a highly purified botulinum toxin, without other clostridial proteins (hemagglutinins and nonhemagglutinins). IncobotulinumtoxinA has proven its efficacy and duration over time, maintaining response after multiple treatment cycles.

CONCLUSION
This recommendation provides up-to-date information on the use of INCO for aesthetic treatment, focusing on the differential properties of this product regarding its purity, performance, customization, and patient satisfaction.
Versatility of OnabotulinumtoxinA in Aesthetic Medicine
Authors: Brin Mitchell F. , Maltman John , Chapman Mary Ann , Sangha Sara 
Published: August 2024

BACKGROUNDOnabotulinumtoxinA is an injectable product that was introduced into medicine in the 1970s and has been the subject of thousands of clinical and nonclinical publications.OBJECTIVETo review the data related to the versatility of onabotulinumtoxinA in medical aesthetics.METHODSPubMed was searched to identify literature evaluating the effects of onabotulinumtoxinA, with preference given to randomized, placebo-controlled trials and safety meta-analyses.RESULTSOnabotulinumtoxinA is effective and safe across multiple facial indications, racial and ethnic groups, age groups, genders, and facial line severities. Patient-reported outcomes have been prioritized in aesthetic clinical trials and indicate high patient satisfaction and appearance-related psychological outcomes. Integrated safety meta-analysis and immunogenicity analyses have documented acceptable adverse event rates and low immunogenicity of onabotulinumtoxinA.CONCLUSIONOnabotulinumtoxinA is a versatile aesthetic product supported by a strong literature base and positive physician and patient-reported outcomes that reflect a meaningful impact on patient’s quality of life.
Pregnancy and fertility in people with cystic fibrosis following lung transplantation
Authors: Taylor-Cousar Jennifer L. , Sole Amparo , Jain Raksha 
Published: August 2024

Purpose of review
The purpose of this review is to summarize available data on fertility, fertility preservation, pregnancy and parenthood following lung transplantation for people with cystic fibrosis (pwCF).

Recent findings
In the era of cystic fibrosis transmembrane conductance regulator (CFTR) modulator use, oral therapies that positively impact fundamental CFTR protein abnormalities, the number of pregnancies has increased dramatically with a concomitant decrease in lung transplantation. Nonetheless, some pwCF still require lung transplantation as a life-saving measure, and a fraction of those individuals desires parenthood. Cystic fibrosis (CF) providers infrequently discuss fertility preservation with pwCF, and pwCF feel uneducated about their fertility options posttransplant. However, because the immunosuppression required to successfully maintain lung allografts may impact future fertility, pwCF should receive genetic and reproductive counseling prior to lung transplantation. While pregnancies posttransplantation are high-risk, selected females with CF may be able to pursue this path to parenthood.

Summary
Although there is a paucity of data specific to pwCF who have undergone lung transplantation, recently developed general guidelines should inform discussions regarding fertility, pregnancy and parenthood in pwCF who desire parenthood following lung transplantation for optimal shared decision-making.
Organomics
Authors: Salimi Yazdan , Hajianfar Ghasem , Mansouri Zahra , Sanaat Amirhosein , Amini Mehdi , Shiri Isaac , Zaidi Habib 
Published: August 2024

PurposeNon–small cell lung cancer is the most common subtype of lung cancer. Patient survival prediction using machine learning (ML) and radiomics analysis proved to provide promising outcomes. However, most studies reported in the literature focused on information extracted from malignant lesions. This study aims to explore the relevance and additional value of information extracted from healthy organs in addition to tumoral tissue using ML algorithms.Patients and MethodsThis study included PET/CT images of 154 patients collected from available online databases. The gross tumor volume and 33 volumes of interest defined on healthy organs were segmented using nnU-Net deep learning–based segmentation. Subsequently, 107 radiomic features were extracted from PET and CT images (Organomics). Clinical information was combined with PET and CT radiomics from organs and gross tumor volumes considering 19 different combinations of inputs. Finally, different feature selection (FS; 5 methods) and ML (6 algorithms) algorithms were tested in a 3-fold data split cross-validation scheme. The performance of the models was quantified in terms of the concordance index (C-index) metric.ResultsFor an input combination of all radiomics information, most of the selected features belonged to PET Organomics and CT Organomics. The highest C-index (0.68) was achieved using univariate C-index FS method and random survival forest ML model using CT Organomics + PET Organomics as input as well as minimum depth FS method and CoxPH ML model using PET Organomics as input. Considering all 17 combinations with C-index higher than 0.65, Organomics from PET or CT images were used as input in 16 of them.ConclusionsThe selected features and C-indices demonstrated that the additional information extracted from healthy organs of both PET and CT imaging modalities improved the ML performance. Organomics could be a step toward exploiting the whole information available from multimodality medical images, contributing to the emerging field of digital twins in health care.
PET/CT Manifestations of a Case of Cavernous Hemangioma Misdiagnosed as Reproductive Tumor
Authors: Liu Tao , Cheng You , Huang Jian-Jiang , Shao Dan , Wang Si-yun 
Published: August 2024

Abstract
Cavernous hemangioma of mediastinum is a rare, benign tumor originating from vascular endothelial cells. It typically arises in the anterior mediastinum but has also been reported in the posterior mediastinum or the middle mediastinum, and occasionally involves both the anterior and middle compartments. We present the case of a 20-year-old man with a cavernous hemangioma of mediastinum initially misdiagnosed as a reproductive tumor by 18F-FDG PET/CT.
Increase 68Ga-FAPI Uptake in Urogenital Tuberculosis
Authors: Yu Qiuming , Xie Qiang , Zhu Xingxing , Wang Xuemei , Ni Ming 
Published: August 2024

Abstract
Urogenital tuberculosis is one of common sites of extrapulmonary tuberculosis. A 60-year-old man with an elevated prostate-specific antigen level underwent multiparametric MRI, which revealed abnormal signals in the prostate. However, the 68Ga-PSMA PET/CT results were unrevealing. Subsequent 68Ga-FAPI PET/CT imaging revealed intense radioactivity uptake in the prostate and mild radioactivity uptake in the left kidney, which was eventually proven due to tuberculosis.
ARHGAP12 suppresses F-actin assembly to control epithelial tight junction mechanics and paracellular leak pathway permeability
Authors: Tambrin Hana Maldivita , Liu Yun , Zhu Kexin , Teng Xiang , Toyama Yusuke , Miao Yansong , Ludwig Alexander 
Published: August 2024

AbstractTight junctions (TJ) separate body compartments and control the paracellular transport of ions, solutes, and macromolecules across epithelial barriers. There is evidence that claudin-based ion transport (the pore pathway) and the paracellular transport of macromolecules (the leak pathway) are independently regulated processes. However, how leak pathway permeability is controlled is not well understood. Here we have identified the Cdc42/Rac GTPase activating protein ARHGAP12 as a novel and specific regulator of the leak pathway. ARHGAP12 is recruited to TJ via an interaction between its SH3 domain and the TJ protein ZO-2. Using a combination of biochemical and biophysical approaches, in vitro actin polymerisation assays, and permeability assays in MDCK-II cells, we show that ARHGAP12 suppresses N-WASP-mediated F-actin assembly at TJ to dampen junctional tension. This promotes paracellular leak pathway permeability without affecting ion flux. Mechanistically, we demonstrate that the ARHGAP12 tandem WW domain interacts directly and in a multivalent manner with an array of PPxR motifs in the proline-rich domain of N-WASP. This interaction is sufficient to suppress SH3 domain-mediated N-WASP oligomerisation and Arp2/3-driven F-actin assembly in vitro. Collectively our data demonstrate a critical role for ARHGAP12 in suppressing junctional F-actin assembly and tension to promote the flux of small macromolecules across the TJ.
A forward genetic screen identifies Sirtuin1 as a driver of neuroendocrine prostate cancer
Authors: de Almeida Francisca Nunes , Vasciaveo Alessandro , Antao Ainsley Mike , Zou Min , Di Bernardo Matteo , de Brot Simone , Rodriguez-Calero Antonio , Chui Alexander , Wang Alexander L.E. , Floc’h Nicolas , Kim Jaime Y. , Afari Stephanie N. , Mukhammadov Timur , Arriaga Juan Martín , Lu Jinqiu , Shen Michael M. , Rubin Mark A. , Califano Andrea , Abate-Shen Cory 
Published: August 2024

AbstractAlthough localized prostate cancer is relatively indolent, advanced prostate cancer manifests with aggressive and often lethal variants, including neuroendocrine prostate cancer (NEPC). To identify drivers of aggressive prostate cancer, we leveragedSleeping Beauty (SB)transposon mutagenesis in a mouse model based on prostate-specific loss-of-function ofPtenandTp53. Compared with control mice,SBmice developed more aggressive prostate tumors, with increased incidence of metastasis. Notably, a significant percentage of theSBprostate tumors display NEPC phenotypes, and the transcriptomic features of theseSBmouse tumors recapitulated those of human NEPC. We identified commonSBtransposon insertion sites (CIS) and prioritized associated CIS-genes differentially expressed in NEPC versus non-NEPCSBtumors. Integrated analysis of CIS-genes encoding for proteins representing upstream, post-translational modulators of master regulators controlling the transcriptional state ofSB-mouse and human NEPC tumors identifiedsirtuin 1(Sirt1) as a candidate mechanistic determinant of NEPC. Gain-of-function studies in human prostate cancer cell lines confirmed that SIRT1 promotes NEPC, while its loss-of-function or pharmacological inhibition abrogates NEPC. This integrative analysis is generalizable and can be used to identify novel cancer drivers for other malignancies.SummaryUsing an unbiased forward mutagenesis screen in an autochthonous mouse model, we have investigated mechanistic determinants of aggressive prostate cancer. SIRT1 emerged as a key regulator of neuroendocrine prostate cancer differentiation and a potential target for therapeutic intervention.
Stepwise Bayesian Machine Learning Uncovers a Novel Gene Regulatory Network Component in Neural Tube Development
Authors: Xing Chen , Sakumura Yuichi , Kokaji Toshiya , Kunida Katsuyuki , Sasai Noriaki 
Published: August 2024

AbstractRecent advancements in machine learning-based data processing techniques have facilitated the inference of gene regulatory interactions and the identification of key genes from multidimensional gene expression data. In this study, we applied a stepwise Bayesian framework to uncover a novel regulatory component involved in differentiation of specific neural and neuronal cells. We treated naive neural precursor cells with Sonic Hedgehog (Shh) at various concentrations and time points, generating comprehensive whole-genome sequencing data that captured dynamic gene expression profiles during differentiation. The genes were categorized into 224 subsets based on their expression profiles, and the relationships between these subsets were extrapolated. To accurately predict gene regulation among subsets, known networks were used as a core model and subsets to be added were tested stepwise. This approach led to the identification of a novel component involved in neural tube patterning within gene regulatory networks (GRNs), which was experimentally validated. Our study highlights the effectiveness of in silico modeling for extrapolating GRNs during neural development.
c-Abl Kinase Targets Tight Junction Protein ZO-2 in Regulation of Cell Migration and Morphology
Authors: Choi Doo Eun , Gweon Bomi , Notbohm Jacob , Liu Xue-song , Fredberg Jeffrey J. 
Published: August 2024

Abstractc-Abl is a non-receptor tyrosine kinase involved in the regulation of cell migration and morphogenesis, but underlying mechanism remains unclear. Here, we report the identification of tight junction protein ZO-2 as a bona fide substrate of c-Abl. We show that c-Abl directly binds to and phosphorylates the C-terminus of ZO-2. In addition, c-Abl stimulates the activity of JAK1, which subsequently phosphorylates the N-terminus of ZO-2. Using the RNAi-mediated knockdown/rescue strategy, we demonstrate that c-Abl regulates cellular morphology and migration through targeting ZO-2 for phosphorylation. c-Abl activity is also associated with decreased traction forces exerted on the cell substrate and reduced monolayer tension, thus corroborating c-Abl kinase activity-mediated inhibition of cell migration. Collectively, our data uncover ZO-2 as a novel mediator for c-Abl-dependent regulation of cell migration.
Spatial model of cell-fate choice uncovers strong links between tissue morphology and tissue regeneration
Authors: Mani Somya , Tlusty Tsvi 
Published: August 2024

Tissues in multicellular organisms are immensely diverse: animal tissues include sheet-like epithelia, bundles of syncitial muscle fibres and the branched and interconnected nerves, while plants contain sheet-like epidermis and highly organized bundles of vascular tissue. However, at the microanatomical level, tissues are notably similar in that they are organized into distinct domains: domains are characterized by their cellular compositions and hold precise adjacency relations among each other. These morphological similarities are surprising because multicellularity has evolved multiple times independently. Separately, tissues also hold a remarkable functional similarity: across all multicellular organisms, including poor regenerators such as mammals, tissues routinely heal from injuries. The cellular organization within tissues, as well as the ability regenerate result from developmental processes: cells divide, die, differentiate and migrate according to cues they receive from their neighborhoods.We ask two interlinked questions: What diversity of tissue morphology can simple developmental processes generate? And is tissue morphology related to tissue regeneration? We address these questions using an agent based model of cell-fate decisions where cells use simple rules to respond to their cellular neighborhoodsOur model produces a rich diversity of tissue morphologies: By simply tuning the density of cellular interactions and the propensity of cellular differentiation, we produce tissues that go from disordered and sparse to tissues organized into dense and contiguous domains. Importantly, tissue morphology was strongly linked to regeneration in the model: the ability to heal was highly enriched in densely packed, contiguous tissues. Moreover, the predominant mode of tissue healing in the model recapitulates natural mechanisms: tissues healed through the replacement of injured cells through cell-division in adjacent regions. Our work generates experimentally testable predictions on the effects of manipulating cellular interactions on tissue morphology and in turn, on tissue regeneration.
Replicated blood-based biomarkers for Myalgic Encephalomyelitis not explicable by inactivity
Authors: Beentjes Sjoerd Viktor , Kaczmarczyk Julia , Cassar Amanda , Samms Gemma Louise , Hejazi Nima S. , Khamseh Ava , Ponting Chris P. 
Published: August 2024

AbstractMyalgic Encephalomyelitis (ME; sometimes referred to as chronic fatigue syndrome [CFS]) is a relatively common and female-biased disease of unknown pathogenesis that profoundly decreases patients’ health-related quality-of-life. ME/CFS diagnosis is hindered by the absence of robustly-defined and specific biomarkers that are easily measured from available sources such as blood, and unaffected by ME/CFS patients’ low level of physical activity. Previous studies of blood biomarkers have not yielded replicated results, perhaps due to low study sample sizes (n <100). Here, we use UK Biobank (UKB) data for up to 1,455 ME/CFS cases and 131,303 population controls to discover hundreds of molecular and cellular blood traits that differ significantly between cases and controls. Importantly, 116 of these traits are replicated, as they are significant for both female and male cohorts. Our analysis used semi-parametric efficient estimators, an initial Super Learner fit followed by a one-step correction, three types of mediators, and natural direct and indirect estimands, to decompose the average effect of ME/CFS status on molecular and cellular traits. Strikingly, these trait differences cannot be explained by ME/CFS cases’ restricted activity. Of 3,237 traits considered, ME/CFS status had a significant effect on only one, via the “Duration of walk” (UKB field 874) mediator. By contrast, ME/CFS status had a significant direct effect on 290 traits (9%). As expected, these effects became more significant with increased stringency of case and control definition. Significant female and male traits were indicative of chronic inflammation, insulin resistance and liver disease. Individually, significant effects on blood traits, however, were not sufficient to cleanly distinguish cases from controls. Nevertheless, their large number, lack of sex-bias, and strong significance, despite the ‘healthy volunteer’ selection bias of UKB participants, keep alive the future ambition of a blood-based biomarker panel for accurate ME/CFS diagnosis.
The Effects of Social Distancing Policy on the Changes of Floating Population in Korea
Authors: Oh Jaehwan , Choi Minsu , Lee Kwang-soo 
Published: August 2024

AbstractObjectivesIn response to the World Health Organization’s declaration of the COVID-19 pandemic in March 2020, nations worldwide, including Korea, implemented social distancing as a critical Non-Pharmaceutical Intervention (NPI) to curb the spread of the disease. Social distancing measures aimed to reduce person-to-person contact through various strategies such as facility restrictions, gathering limitations, travel bans, and lockdowns.MethodsThis study investigated the impact of social distancing policies on the floating population across 229 administrative districts in Korea. The dependent variable was the total floating population, while the independent variable was the social distancing stage of the week, focusing on stages that prevailed for more than half of each week. Control variables included sex ratio, season, and the number of weekly holidays.ResultsDescriptive analysis and t-tests were conducted to examine the variables, and Panel GEE analysis was performed to analyze changes in the floating population with the social distancing stage. The analysis revealed a significant decrease in the floating population when transitioning from stage 5 to stage 4 of social distancing. This indicates that stricter gathering restrictions and increased local government autonomy effectively reduced person- to-person contact.DiscussionThese findings underscore the importance of targeted social distancing measures in mitigating transmission risks during infectious disease outbreaks. The study provides valuable insights for future policymaking on infectious diseases, offering relevant data to inform effective public health strategies and responses. Understanding the impacts of such measures can help refine approaches to managing future pandemics and ensuring public health safety.
Common DNA sequence variation influences epigenetic aging in African populations
Authors: Meeks Gillian L. , Scelza Brooke , Asnake Hana M. , Prall Sean , Patin Etienne , Froment Alain , Fagny Maud , Quintana-Murci Lluis , Henn Brenna M. , Gopalan Shyamalika 
Published: August 2024

AbstractAging is associated with genome-wide changes in DNA methylation in humans, facilitating the development of epigenetic age prediction models. However, most of these models have been trained primarily on European-ancestry individuals, and none account for the impact of methylation quantitative trait loci (meQTL). To address these gaps, we analyzed the relationships between age, genotype, and CpG methylation in 3 understudied populations: central African Baka (n = 35), southern African ‡Khomani San (n = 52), and southern African Himba (n = 51). We find that published prediction methods yield higher mean errors in these cohorts compared to European-ancestry individuals, and find that unaccounted-for DNA sequence variation may be a significant factor underlying this loss of accuracy. We leverage information about the associations between DNA genotype and CpG methylation to develop an age predictor that is minimally influenced by meQTL, and show that this model remains accurate across a broad range of genetic backgrounds. Intriguingly, we also find that the older individuals and those exhibiting relatively lower epigenetic age acceleration in our cohorts tend to carry more epigenetic age-reducing genetic variants, suggesting a novel mechanism by which heritable factors can influence longevity.
MED26-enriched condensates drive erythropoiesis through modulating transcription pausing
Authors: Zhu Shicong , Zhang Xiaoting , Li Na , Zhao Xinying , Li Man , Xie Si , Yue Qiuyu , Li Yunfeng , Li Dong , Wu Fan , Zhang Zile , Feng Ziqi , Zhang Yiyang , Choi Wonhyung , Jia Xinyi , Deng Yuelin , Hu Qi , Yao Xingyun , Gao Xiaofei , Lee Hsiang-Ying 
Published: August 2024

AbstractThe Mediator complex regulates various aspects of hematopoietic development, but whether composition of the Mediator complex undergoes dynamic changes for diversifying transcription and functional outputs is unknown. Here, we found that MED26, a subunit in the core Mediator complex, played a distinctive role in facilitating transcription pausing essential for erythroid development. While most Mediator subunits drastically decreased during this process, MED26 remained relatively abundant. Intriguingly, in the early stages, more than half of MED26 occupancy sites did not co-localize with MED1, a representative Mediator subunit, suggesting these subunits exert context-dependent gene regulation. We revealed that MED26-enriched loci were associated with RNA polymerase Ⅱ pausing. MED26 manifested a markedly preferential recruitment of pausing-related factors, leading to an increase in Pol Ⅱ pausing critical for genome-wide transcription repression during erythropoiesis. Moreover, MED26 exhibited pronounced condensate-forming capability, which was necessary for its function in promoting erythropoiesis and recruiting pausing-related factors. Collectively, this study provides mechanistic insights into the functional coordination of distinct Mediator subunits during development and highlights the switch of transcription condensates towards a MED26 enriched form, which modulates transcription pausing to facilitate transcription repression and erythroid development.