bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emotional dysregulation in women with endometriosis with cyclical and non-cyclical chronic pelvic pain
Authors: Rodríguez-Lozano Dulce Carolina , Meza-Rodríguez María del Pilar , Cruz-Orozco Olivier Paul , Sánchez-Ramírez Brenda , Olguin-Ortega Andrea , Silvestri-Tomassoni José Roberto , Corona-Barsse Guillermo , Escobar-Ponce Luis Fernando , Solis-Paredes Juan Mario , Dominguez-Trejo Benjamín , Camacho-Arroyo Ignacio 
Published: December 2022

Abstract
Background
Endometriosis is a pathophysiological condition characterized by glands and stroma outside the uterus in regions such as the bladder, ureter, fallopian tubes, peritoneum, ovaries, and even in extra pelvic sites. One of the main clinical problems of endometriosis is chronic pelvic pain (CPP), which considerably affects the patients’ quality of life. Patients with endometriosis may, cyclically or non-cyclically (80% of cases) experience CPP. High levels of anxiety and depression have been described in patients with endometriosis related to CPP; however, this has not been evaluated in endometriosis women with different types of CPP. Therefore, the research question of this study was whether there is a difference in the emotional dysregulation due to the type of pain experienced by women with endometriosis?

Methods
This work was performed in the National Institute of Perinatology (INPer) in Mexico City from January 2019 to March 2020 and aimed to determine if there are differences in emotional dysregulation in patients with cyclical and non-cyclical CPP. 49 women from 18 to 52 years-old diagnosed with endometriosis presenting cyclical and non-cyclical CPP answered several batteries made up of Mini-Mental State Examination, Visual Analog Scale, Beck's Depression Inventory, State Trait-Anxiety Inventory, and Generalized Anxiety Inventory. Mann–Whitney U and Student’s t-test for independent samples to compare the difference between groups was used. Relative risk estimation was performed to determine the association between non-cyclical and cyclical CPP with probability of presenting emotional dysregulation.

Results
We observed that patients with non-cyclical CPP exhibited higher levels of depression and anxiety (trait-state and generalized anxiety) than patients with cyclical pain, p < 0.05 was considered significant. No differences were observed in pain intensity, but there was a higher probability of developing emotional dysregulation (anxiety or depression) in patients with non-cyclical CPP. No differences were observed in cognitive impairment.

Conclusions
Our data suggest that patients with non-cyclical (persistent) CPP present a higher emotional dysregulation than those with cyclical pain.
A real-world economic analysis of biologic therapies for psoriatic arthritis in Italy: results of the CHRONOS observational longitudinal study
Authors: Zagni Emanuela , Frassi Micol , Mariano Giuseppa Pagano , Fusaro Enrico , Lomater Claudia , Del Medico Patrizia , Iannone Florenzo , Foti Rosario , Limonta Massimiliano , Marchesoni Antonio , Raffeiner Bernd , Viapiana Ombretta , Grassi Walter , Grembiale Rosa Daniela , Guggino Giuliana , Mazzone Antonino , Tirri Enrico , Perricone Roberto , Sarzi Puttini Pier Carlo , De Vita Salvatore , Conti Fabrizio , Zullo Alessandro , Simoni Lucia , Fiocchi Martina , Orsenigo Roberto , Colombo Delia 
Published: December 2022

AbstractBackgroundPsoriatic arthritis (PsA) is a chronic, immune-mediated, spondyloarthropathy characterised by musculoskeletal signs and symptoms with associated joint pain and tenderness. The average worldwide PsA prevalence is 133/100,000, while in the Italian population is 90–420/100,000.Traditionally, nonsteroidal anti-inflammatory drugs, glucocorticoid, and disease-modifying antirheumatic drugs have been used in the treatment of PsA. However, for those patients who are not adequately controlled with conventional therapies, the new biologics compounds represent a valid option. Biologic therapies have been shown to be more effective but also more expensive than conventional systemic treatments. Based on the CHRONOS study, the economic analyses presented in this paper aim to assess the annualised direct costs and the cost-per-responder of biologics in a real-world context assuming the Italian National Health System perspective.MethodsThe economic assessments were carried out on the overall cohort of patients, and on the tumour necrosis factor alpha inhibitors (TNFi) and the secukinumab subgroup, the most prescribed biologic therapies within the CHRONOS study.ResultsThe annual economic impact of PsA in the overall group was €12,622, €11,725 in the secukinumab subgroup, and €12,791 in the TNFi subgroup. Biologics absorbed the main expenditure costs in the treatment of PsA accounting for about the 93% of total costs. At 6 months, secukinumab performed better in all the considered outcomes: cost-per-responder according to EULAR DAS28 and ACR50 response criteria were €12,661- €28,975, respectively, while they were €13,356 - €33,368 in the overall cohort and €13,138 - €35,166 in the TNFi subgroup. At 12 months secukinumab remained the subgroup with the lowest cost-per-responder ratio in EULAR DAS28 and ACR50 response criteria, while TNFi subgroup was the lowest one considered the ACR20.ConclusionDespite some potential methodological limitations, our cost-per-response analysis provides physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.
Echolocating bats rapidly adjust their mouth gape to control spatial acquisition when scanning a target
Authors: Eitan Ofri , Taub Mor , Boonman Arjan , Zviran Amir , Tourbabin Vladimir , Weiss Anthony J. , Yovel Yossi 
Published: December 2022

Abstract
Background
As well known to any photographer, controlling the “field of view” offers an extremely powerful mechanism by which to adjust target acquisition. Only a few natural sensory systems can actively control their field of view (e.g., dolphins, whales, and bats). Bats are known for their active sensing abilities and modify their echolocation signals by actively controlling their spectral and temporal characteristics. Less is known about bats’ ability to actively modify their bio-sonar field of view.

Results
We show that Pipistrellus kuhlii bats rapidly narrow their sensory field of view (i.e., their bio-sonar beam) when scanning a target. On-target vertical sonar beams were twofold narrower than off-target beams. Continuous measurements of the mouth gape of free-flying bats revealed that they control their bio-sonar beam by a ~3.6 mm widening of their mouth gape: namely, bats open their mouth to narrow the beam and vice versa.

Conclusions
Bats actively and rapidly control their echolocation vertical beam width by modifying their mouth gape. We hypothesize that narrowing their vertical beam narrows the zone of ensonification when estimating the elevation of a target. In other words, bats open their mouth to improve sensory localization.
Sex-specific expression of pheromones and other signals in gravid starfish
Authors: Jönsson Mathias , Morin Marie , Wang Conan K. , Craik David J. , Degnan Sandie M. , Degnan Bernard M. 
Published: December 2022

Abstract
Background
Many echinoderms form seasonal aggregations prior to spawning. In some fecund species, a spawning event can lead to population outbreaks with detrimental ecosystem impacts. For instance, outbreaks of crown-of-thorns starfish (COTS), a corallivore, can destroy coral reefs. Here, we examine the gene expression in gravid male and female COTS prior to spawning in the wild, to identify genome-encoded factors that may regulate aggregation and spawning. This study is informed by a previously identified exoproteome that attracts conspecifics. To capture the natural gene expression profiles, we isolated RNAs from gravid female and male COTS immediately after they were removed from the Great Barrier Reef.

Results
Sexually dimorphic gene expression is present in all seven somatic tissues and organs that we surveyed and in the gonads. Approximately 40% of the exoproteome transcripts are differentially expressed between sexes. Males uniquely upregulate an additional 68 secreted factors in their testes. A suite of neuropeptides in sensory organs, coelomocytes and gonads is differentially expressed between sexes, including the relaxin-like gonad-stimulating peptide and gonadotropin-releasing hormones. Female sensory tentacles—chemosensory organs at the distal tips of the starfish arms—uniquely upregulate diverse receptors and signalling molecules, including chemosensory G-protein-coupled receptors and several neuropeptides, including kisspeptin, SALMFamide and orexin.

Conclusions
Analysis of 103 tissue/organ transcriptomes from 13 wild COTS has revealed genes that are consistently differentially expressed between gravid females and males and that all tissues surveyed are sexually dimorphic at the molecular level. This finding is consistent with female and male COTS using sex-specific pheromones to regulate reproductive aggregations and synchronised spawning events. These pheromones appear to be received primarily by the sensory tentacles, which express a range of receptors and signalling molecules in a sex-specific manner. Furthermore, coelomocytes and gonads differentially express signalling and regulatory factors that control gametogenesis and spawning in other echinoderms.
Berberine increases stromal production of Wnt molecules and activates Lgr5+ stem cells to promote epithelial restitution in experimental colitis
Authors: Luo Zecheng , Li Zihao , Liang Zheng , Wang Lin , He Guanlin , Wang Dongdi , Shen Lei , Wang Zhengting , Ma Xiuying , Geng Funeng , Wang Haozhong , Liu Wenping , Liu Huijuan , Li Baojie 
Published: December 2022

Abstract
Background
Inflammatory bowel diseases (IBDs) are characterized by sustained inflammation and/or ulcers along the lower digestive tract, and have complications such as colorectal cancer and inflammation in other organs. The current treatments for IBDs, which affect 0.3% of the global population, mainly target immune cells and inflammatory cytokines with a success rate of less than 40%.

Results
Here we show that berberine, a natural plant product, is more effective than the frontline drug sulfasalazine in treating DSS (dextran sulfate sodium)-induced colitis in mice, and that berberine not only suppresses macrophage and granulocyte activation but also promotes epithelial restitution by activating Lgr5+ intestinal stem cells (ISCs). Mechanistically, berberine increases the expression of Wnt genes in resident mesenchymal stromal cells, an ISC niche, and inhibiting Wnt secretion diminishes the therapeutic effects of berberine. We further show that berberine controls the expression of many circadian rhythm genes in stromal cells, which in turn regulate the expression of Wnt molecules.

Conclusions
Our findings suggest that berberine acts on the resident stromal cells and ISCs to promote epithelial repair in experimental colitis and that Wnt-β-Catenin signaling may be a potential target for colitis treatment.
Contraceptive use and contraceptive counselling interventions for women of reproductive age with cancer: a systematic review and meta-analysis
Authors: Harris Melissa L. , Feyissa Tesfaye R. , Bowden Nikola A. , Gemzell-Danielsson Kristina , Loxton Deborah 
Published: December 2022

Abstract
Background
A lack of clarity exists regarding contraceptive uptake and counselling among women with cancer, despite these women having unique family planning needs. This study aimed to systematically review the available literature and produce an overall summary estimate of contraceptive use and counselling among women with cancer across the cancer care continuum.

Methods
A systematic search of articles reporting on contraceptive counselling and/or contraceptive use among women of reproductive age (15–49 years) with cancer across the cancer care continuum (e.g. diagnosis, treatment, survivorship) was conducted in MEDLINE, Embase, CINAHL, Maternity and Infant Care and Cochrane Library. Two independent reviewers conducted the data screening, data extraction and risk of bias assessment. Qualitative synthesis and meta-analyses were conducted to summarise the key findings.

Results
We included 21 articles involving 3835 participants in this review. Studies varied according to the cancer population and time along the cancer care continuum it was assessed. Of the studies that reported the overall contraceptive prevalence among women diagnosed with cancer (n = 8), contraceptive use ranged from 25 to 92%. Of the four studies that focused on cancer survivors, the contraceptive prevalence ranged from 47 to 84%. When the prevalence of these studies was pooled, a crude summary prevalence of 64% (62% among women with cancer versus 68% among cancer survivors) was found. The rate of contraceptive counselling was assessed in ten studies. A pooled prevalence of 50% (44% among women with cancer versus 58% among cancer survivors) was found, with the prevalence ranging from 12 to 78% among individual studies depending on the point in the cancer care continuum that it was provided. When contraceptive counselling was provided, it was found to significantly increase contraceptive use although biases were identified in its application.

Conclusions
Contraceptive counselling interventions as part of standard cancer care have the potential to not only empower women with cancer and cancer survivors to make informed choices regarding their reproductive health but also provide the ability to plan future pregnancies for times of better health.
Construction of a ferroptosis-related signature based on seven lncRNAs for prognosis and immune landscape in clear cell renal cell carcinoma
Authors: Wei Shi-Yao , Feng Bei , Bi Min , Guo Hai-Ying , Ning Shang-Wei , Cui Rui 
Published: December 2022

AbstractBackgroundRecent studies have demonstrated that long non-coding RNAs (lncRNAs) are involved in regulating tumor cell ferroptosis. However, prognostic signatures based on ferroptosis-related lncRNAs (FRLs) and their relationship to the immune microenvironment have not been comprehensively explored in clear cell renal cell carcinoma (ccRCC).MethodsIn the present study, the expression profiles of ccRCC were acquired from The Cancer Genome Atlas (TCGA) database; 459 patient specimens and 69 adjacent normal tissues were randomly separated into training or validation cohorts at a 7:3 ratio. We identified 7 FRLs that constitute a prognostic signature according to the differential analysis, correlation analysis, univariate regression, and least absolute shrinkage and selection operator (LASSO) Cox analysis. To identify the independence of risk score as a prognostic factor, univariate and multivariate regression analyses were also performed. Furthermore, CIBERSORT was conducted to analyze the immune infiltration of patients in the high-risk and low-risk groups. Subsequently, the differential expression of immune checkpoint and m6A genes was analyzed in the two risk groups.ResultsA 7-FRLs prognostic signature of ccRCC was developed to distinguish patients into high-risk and low-risk groups with significant survival differences. This signature has great prognostic performance, with the area under the curve (AUC) for 1, 3, and 5 years of 0.713, 0.700, 0.726 in the training set and 0.727, 0.667, and 0.736 in the testing set, respectively. Moreover, this signature was significantly associated with immune infiltration. Correlation analysis showed that risk score was positively correlated with regulatory T cells (Tregs), activated CD4 memory T cells, CD8 T cells and follicular helper T cells, whereas it was inversely correlated with monocytes and M2 macrophages. In addition, the expression of fourteen immune checkpoint genes and nine m6A-related genes varied significantly between the two risk groups.ConclusionWe established a novel FRLs-based prognostic signature for patients with ccRCC, containing seven lncRNAs with precise predictive performance. The FRLs prognostic signature may play a significant role in antitumor immunity and provide a promising idea for individualized targeted therapy for patients with ccRCC.
Long noncoding RNA HOTAIR facilitates pulmonary vascular endothelial cell apoptosis via DNMT1 mediated hypermethylation of Bcl-2 promoter in COPD
Authors: Dai Zhongshang , Liu Xiangming , Zeng Huihui , Chen Yan 
Published: December 2022

Abstract
Background
To study the regulatory effect of Long non-coding RNA (LncRNA) HOX transcript antisense RNA (HOTAIR) on pulmonary vascular endothelial cell (HPVEC) apoptosis and determine whether the HOTAIR facilitate HPVEC apoptosis via DNMT1 mediated hypermethylation of Bcl-2 promoter in chronic obstructive pulmonary disease (COPD).

Methods
LncRNA array was used to measure the differentially expressed lncRNAs in COPD and non-COPD lung tissues. Expression of HOTAIR in COPD patient lungs and cigarette smoke extract (CSE)-induced HPVEC was assessed by qRT-PCR. The location of HOTAIR was determined in COPD patient lungs and HPVEC by RNA in situ hybridization (RNA-ISH). The emphysema mouse model and HOTAIR knockdown mice were each established by inhaling cigarette smoke or intratracheal lentiviral vectors instillation. The dysregulation of DNA methyltransferase enzyme 1 (DNMT1), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and Cleaved-caspase 3 protein expression were detected by Western blotting. HOTAIR, DNMT1, Bcl-2 and Bax mRNA expression were measured by quantitative real-time polymerase chain reaction. TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays were used to assess apoptotic ratio in mice and CSE-induced HPVEC. Methylation-specific PCR (MSP) assay was conducted to observe the alterations in the methylation of the Bcl-2 promoter in specimens. RNA pull-down assay was used for analysis of the correlation between HOTAIR and DNMT1.

Results
The expression levels of the HOTAIR were up-regulated in COPD patient lungs and CSE-induced HPVEC. HPVEC apoptosis with down-regulated Bcl-2 expression, increased promoter methylation, DNMT1, Bax and Cleaved-caspase 3 expression was found in emphysema mouse model and CSE-induced HPVEC. Knockdown HOTAIR can attenuate cell apoptosis and emphysema via DNMT1 mediated hypermethylation of Bcl-2 promoter in mice. In vitro, HOTAIR can aggravate the apoptosis of CSE-exposed HPVEC. DNMT1 was a target of HOTAIR and had a positive correlation with HOTAIR.

Conclusion
HOTAIR facilitates HPVEC apoptosis via DNMT1 mediated hypermethylation of Bcl-2 promoter in COPD, and attenuating the expression of HOTAIR may be a new therapy to prevent COPD.
Safety and efficacy of RT234 vardenafil inhalation powder on exercise parameters in pulmonary arterial hypertension: phase II, dose-escalation study design
Authors: Benza Raymond L. , Franco Veronica , Aras Mandar A. , Spikes Leslie , Grinnan Daniel , Satler Carol 
Published: December 2022

Abstract
Background
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by high mean pulmonary arterial pressure (≥ 20 mmHg) and remodeling of the vascular arteries. Approved therapies improve symptoms and delay clinical worsening in the long term, but they do not relieve acute exertional symptoms. RT234, a drug/device combination (Respira Therapeutics, Palo Alto, CA, USA) that delivers the phosphodiesterase 5 inhibitor vardenafil to the lungs via inhalation, has been shown to reduce pulmonary vascular resistance in patients with PAH. This study aims to evaluate whether RT234 can increase oxygen capacity during cardiopulmonary exercise testing (CPET) in patients with PAH.

Methods
This prospective, multi-center, open-label, two-cohort, dose-escalation, phase IIb trial in patients with PAH will evaluate the safety and efficacy of RT234 in improving exercise parameters. The trial began in September 2020 and is expected to be completed by early 2024. Patients eligible for enrollment will have a right heart catheterization–confirmed diagnosis of PAH, a 6-minute walking distance of ≥ 150 m, a minute ventilation/carbon dioxide production slope of ≥ 36, and will be on up to three stable oral and/or inhaled (not parenteral) PAH-specific background therapies. The estimated sample size is 86 patients, who will be divided into two dose cohorts. Cohort 1 will receive 0.5 mg RT234, and cohort 2 will receive 1.0 mg RT234. Each cohort will contain two subgroups based on the number of PAH background medications (up to two vs three). The trial will assess patients’ changes from baseline in peak oxygen consumption (VO2) during CPET 30 minutes after a single dose of 0.5 mg or 1.0 mg RT234, the change in the 6-minute walking distance, and the pharmacokinetics and safety profile of single doses of RT234.

Conclusion
This is the first trial involving an as-needed medication for PAH. The trial will provide insights into the safety and efficacy of as-needed RT234 in treating the acute symptoms of PAH during exercise and will inform the design of further trials.
Trial registration number: ClinicalTrials.gov identifier NCT04266197.
Sputum from patients with primary ciliary dyskinesia contains high numbers of dysfunctional neutrophils and inhibits efferocytosis
Authors: Blanter Marfa , Cockx Maaike , Wittebols Liesel , Abouelasrar Salama Sara , De Bondt Mirre , Berghmans Nele , Pörtner Noëmie , Vanbrabant Lotte , Lorent Natalie , Gouwy Mieke , Boon Mieke , Struyf Sofie 
Published: December 2022

Abstract
Background
Primary ciliary dyskinesia (PCD) is a genetic disorder characterized by recurrent airway infection and inflammation. There is no cure for PCD and to date there are no specific treatments available. Neutrophils are a crucial part of the immune system and are known to be dysfunctional in many inflammatory diseases. So far, the role of the neutrophils in PCD airways is largely unknown. The purpose of this study was to investigate the phenotype and function of airway neutrophils in PCD, and compare them to blood neutrophils.

Methods
Paired peripheral blood and spontaneously expectorated sputum samples from patients with PCD (n = 32) and a control group of patients with non-PCD, non-cystic fibrosis bronchiectasis (n = 5) were collected. The expression of neutrophil-specific surface receptors was determined by flow cytometry. Neutrophil function was assessed by measuring the extent of actin polymerization, production of reactive oxygen species (ROS) and release of neutrophil extracellular traps (NETs) in response to activating stimuli.

Results
Sputum neutrophils displayed a highly activated phenotype and were unresponsive to stimuli that would normally induce ROS production, actin polymerization and the expulsion of NETs. In addition, PCD sputum displayed high activity of neutrophil elastase, and impaired the efferocytosis by healthy donor macrophages.

Conclusions
Sputum neutrophils in PCD are dysfunctional and likely contribute to ongoing inflammation in PCD airways. Further research should focus on anti-inflammatory therapies and stimulation of efferocytosis as a strategy to treat PCD.
Considerations on dosimetry for in vitro assessment of e-cigarette toxicity
Authors: Forest Valérie , Mercier Clément , Pourchez Jérémie 
Published: December 2022

AbstractElectronic cigarettes (or e-cigarettes) can be used as smoking cessation aid. Some studies tend to show that they are less hazardous than tobacco cigarettes, even if it does not mean they are completely safe. The huge variation in study designs assessing in vitro toxicity of e-cigarettes aerosol makes it difficult to make comparisons and draw robust and irrefutable conclusions. In this paper, we review this heterogeneity (in terms of e-cigarette products, biological models, and exposure conditions) with a special focus on the wide disparity in the doses used as well as in the way they are expressed. Finally, we discuss the major issue of dosimetry and show how dosimetry tools enable to align data between different exposure systems or data from different laboratories and therefore allow comparisons to help further exploring the risk potential of e-cigarettes.