bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular mechanisms regulating natural menopause in the female ovary: a study based on transcriptomic data
Authors: Liu Quan , Wei Fangqin , Wang Jiannan , Liu Haiyan , Zhang Hua , Liu Min , Liu Kaili , Ye Zheng 
Published: July 2023

IntroductionNatural menopause is an inevitable biological process with significant implications for women's health. However, the molecular mechanisms underlying menopause are not well understood. This study aimed to investigate the molecular and cellular changes occurring in the ovary before and after perimenopause.MethodsSingle-cell sequencing data from the GTEx V8 cohort (30-39: 14 individuals; 40-49: 37 individuals; 50-59: 61 individuals) and transcriptome sequencing data from ovarian tissue were analyzed. Seurat was used for single-cell sequencing data analysis, while harmony was employed for data integration. Cell differentiation trajectories were inferred using CytoTrace. CIBERSORTX assessed cell infiltration scores in ovarian tissue. WGCNA evaluated co-expression network characteristics in pre- and post-perimenopausal ovarian tissue. Functional enrichment analysis of co-expression modules was conducted using ClusterprofileR and Metascape. DESeq2 performed differential expression analysis. Master regulator analysis and signaling pathway activity analysis were carried out using MsViper and Progeny, respectively. Machine learning models were constructed using Orange3.ResultsWe identified the differentiation trajectory of follicular cells in the ovary as ARID5B+ Granulosa -&gt; JUN+ Granulosa -&gt; KRT18+ Granulosa -&gt; MT-CO2+ Granulosa -&gt; GSTA1+ Granulosa -&gt; HMGB1+ Granulosa. Genes driving Granulosa differentiation, including RBP1, TMSB10, SERPINE2, and TMSB4X, were enriched in ATP-dependent activity regulation pathways. Genes involved in maintaining the Granulosa state, such as DCN, ARID5B, EIF1, and HSP90AB1, were enriched in the response to unfolded protein and chaperone-mediated protein complex assembly pathways. Increased contents of terminally differentiated HMGB1+ Granulosa and GSTA1+ Granulosa were observed in the ovaries of individuals aged 50-69. Signaling pathway activity analysis indicated a gradual decrease in TGFb and MAPK pathway activity with menopause progression, while p53 pathway activity increased. Master regulator analysis revealed significant activation of transcription factors FOXR1, OTX2, MYBL2, HNF1A, and FOXN4 in the 30-39 age group, and GLI1, SMAD1, SMAD7, APP, and EGR1 in the 40-49 age group. Additionally, a diagnostic model based on 16 transcription factors (Logistic Regression L2) achieved reliable performance in determining ovarian status before and after perimenopause.ConclusionThis study provides insights into the molecular and cellular mechanisms underlying natural menopause in the ovary. The findings contribute to our understanding of perimenopausal changes and offer a foundation for health management strategies for women during this transition.
Effect of gluten-free diet on autoimmune thyroiditis progression in patients with no symptoms or histology of celiac disease: a meta-analysis
Authors: Piticchio Tommaso , Frasca Francesco , Malandrino Pasqualino , Trimboli Pierpaolo , Carrubba Nunzia , Tumminia Andrea , Vinciguerra Federica , Frittitta Lucia 
Published: July 2023

BackgroundHashimoto’s thyroiditis (HT) is the most common autoimmune disease. HT may be associated with nonthyroidal autoimmune diseases, including celiac disease (CD) or other gluten-related conditions (GRC). In the last years, interest about gluten-free diet (GFD) has increased for its supposed extraintestinal anti-inflammatory effect; thus, many patients with HT initiate GFD on their own.ObjectivesThe aim of this meta-analysis is to examine all available data in literature about the effect of a GFD on TgAb, TPOAb, TSH, FT4, and FT3 levels in patients with HT and no symptoms or histology of CD.MethodsThe study was conducted according to MOOSE (Meta-analysis Of Observational Studies in Epidemiology). The search was performed on databases PubMed and Scopus. The last search was performed on 7 February 2023. Quality assessment was performed. Meta-analyses were performed using the random-effect model. Hedges’ g was used to measure the effect size (ES). Statistical analyses were performed using StataSE 17.ResultsThe online search retrieved 409 articles, and 4 studies with a total of 87 patients were finally included for quantitative analysis. The risk of bias was generally low. The mean period of GFD was almost 6 months. The meta-analyses showed reduction in antibody levels with ES: −0.39 for TgAb (95% CI: −0.81 to +0.02; p = 0.06; I² = 46.98%) and −0.40 for TPOAb (95% CI: −0.82 to +0.03; p = 0.07; I² = 47.58%). TSH showed a reduction with ES: −0.35 (95% CI: −0.64 to −0.05; p = 0.02; I² = 0%) and FT4 showed an increase with ES: +0.35% (95% CI: 0.06 to 0.64; p = 0.02; I² = 0%). FT3 did not display variations (ES: 0.05; 95% CI: −0.38 to +0.48; p = 0.82; I² = 51%). The heterogeneity of TgAb, TPOAb, and FT3 data was solved performing sub-analyses between patients with or without GRC (TgAb p = 0.02; TPOAb p = 0.02; FT3 p = 0.04) and only for FT3, performing a sub-analysis between patients taking and not taking LT4 (p = 0.03).ConclusionThis is the first meta-analysis investigating the effect of GFD on HT. Our results seem to indicate a positive effect of the gluten deprivation on thyroid function and its inflammation, particularly in patients with HT and GRC. However, current lines of evidence are not yet sufficient to recommend this dietary approach to all patients with a diagnosis of HT.
The new histological system for the diagnosis of adrenocortical cancer
Authors: Urusova Liliya , Porubayeva Erika , Pachuashvili Nano , Elfimova Alina , Beltsevich Dmitry , Mokrysheva Natalia 
Published: July 2023

IntroductionAdrenocortical cancer (ACC) is a rare malignant tumor that originates in the adrenal cortex. Despite extensive molecular-genetic, pathomorphological, and clinical research, assessing the malignant potential of adrenal neoplasms in clinical practice remains a daunting task in histological diagnosis. Although the Weiss score is the most prevalent method for diagnosing ACC, its limitations necessitate additional algorithms for specific histological variants. Unequal diagnostic value, subjectivity in evaluation, and interpretation challenges contribute to a gray zone where the reliable assessment of a tumor’s malignant potential is unattainable. In this study, we introduce a universal mathematical model for the differential diagnosis of all morphological types of ACC in adults.MethodsThis model was developed by analyzing a retrospective sample of data from 143 patients who underwent histological and immunohistochemical examinations of surgically removed adrenal neoplasms. Statistical analysis was carried out on Python 3.1 in the Google Colab environment. The cutting point was chosen according to Youden’s index. Scikit-learn 1.0.2 was used for building the multidimensional model for Python. Logistical regression analysis was executed with L1-regularization, which is an effective method for extracting the most significant features of the model.ResultsThe new system we have developed is a diagnostically meaningful set of indicators that takes into account a smaller number of criteria from the currently used Weiss scale. To validate the obtained model, we divided the initial sample set into training and test sets in a 9:1 ratio, respectively. The diagnostic algorithm is highly accurate [overall accuracy 100% (95% CI: 96%-100%)].DiscussionOur method involves determining eight diagnostically significant indicators that enable the calculation of ACC development probability using specified formulas. This approach may potentially enhance diagnostic precision and facilitate improved clinical outcomes in ACC management.
Inappropriate therapy of euvolemic hyponatremia, the most frequent type of hyponatremia in SARS-CoV-2 infection, is associated with increased mortality in COVID-19 patients
Authors: Pazos-Guerra Mario , Ruiz-Sánchez Jorge Gabriel , Pérez-Candel Xavier , López-Nevado Celia , Hernández-Olmeda Fernando , Cuesta-Hernández Martin , Martín-Sánchez Javier , Calle-Pascual Alfonso Luis , Runkle-de la Vega Isabelle 
Published: July 2023

IntroductionAdmission hyponatremia, frequent in patients hospitalized for COVID-19, has been associated with increased mortality. However, although euvolemic hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis (SIAD) is the single most common cause of hyponatremia in community-acquired pneumonia (CAP), a thorough and rigorous assessment of the volemia of hyponatremic COVID-19 subjects has yet to be described. We sought to identify factors contributing to mortality and hospital length-of-stay (LOS) in hospitalized COVID-19 patients admitted with hyponatremia, taking volemia into account.MethodRetrospective study of 247 patients admitted with COVID-19 to a tertiary hospital in Madrid, Spain from March 1st through March 30th, 2020, with a glycemia-corrected serum sodium level (SNa) &lt; 135 mmol/L. Variables were collected at admission, at 2nd-3rd day of hospitalization, and ensuing days when hyponatremia persisted. Admission volemia (based on both physical and analytical parameters), therapy, and its adequacy as a function of volemia, were determined.ResultsAge: 68 years [56-81]; 39.9% were female. Median admission SNa was 133 mmol/L [131- 134]. Hyponatremia was mild (SNa 131-134 mmol/L) in 188/247 (76%). Volemia was available in 208/247 patients; 57.2% were euvolemic and the rest (42.8%) hypovolemic. Hyponatremia was left untreated in 154/247 (62.3%) patients. Admission therapy was not concordant with volemia in 43/84 (51.2%). In fact, the majority of treated euvolemic patients received incorrect therapy with isotonic saline (37/41, 90.2%), whereas hypovolemics did not (p=0.001). The latter showed higher mortality rates than those receiving adequate or no therapy (36.7% vs. 19% respectively, p=0.023). The administration of isotonic saline to euvolemic hyponatremic subjects was independently associated with an elevation of in-hospital mortality (Odds Ratio: 3.877, 95%; Confidence Interval: 1.25-12.03).ConclusionHyponatremia in COVID-19 is predominantly euvolemic. Isotonic saline infusion therapy in euvolemic hyponatremic COVID-19 patients can lead to an increased mortality rate. Thus, an exhaustive and precise volemic assessment of the hyponatremic patient with CAP, particularly when due to COVID-19, is mandatory before instauration of therapy, even when hyponatremia is mild.
Assessing the carbon footprint of soccer events through a lightweight CNN model utilizing transfer learning in the pursuit of carbon neutrality
Authors: Liu Zhewei , Guo Dayong 
Published: July 2023

IntroductionSoccer events require a lot of energy, resulting in significant carbon emissions. To achieve carbon neutrality, it is crucial to reduce the cost and energy consumption of soccer events. However, current methods for cost minimization often have high equipment requirements, time-consuming training, and many parameters, making them unsuitable for real-world industrial scenarios. To address this issue, we propose a lightweight CNN model based on transfer learning to study cost minimization strategies for soccer events in a carbon-neutral context.MethodsOur proposed lightweight CNN model uses a downsampling module based on the human brain for efficient information processing and a transfer learning-based module to speed up the training progress. We conducted experiments to evaluate the performance of our model and compared it with existing models in terms of the number of parameters and computation and recognition accuracy.ResultsThe experimental results show that our proposed network model has significant advantages over existing models in terms of the number of parameters and computation while achieving higher recognition accuracy than conventional models. Our model effectively predicts soccer event data and proposes more reasonable strategies to optimize event costs and accelerate the realization of carbon neutral goals.DiscussionOur proposed lightweight CNN model based on transfer learning is a promising method for studying cost minimization strategies for soccer events in a carbon-neutral context. The use of a downsampling module based on the human brain and a transfer learning-based module allows for more efficient information processing and faster training progress. The results of our experiments indicate that our model outperforms existing models and can effectively predict soccer event data and propose cost optimization strategies. Our model can contribute to the realization of carbon-neutral goals in the sports industry.
Emerald ash borer (Agrilus planipennis) infestation bioassays and metabolic profiles of green ash (Fraxinus pennsylvanica) provide evidence for an induced host defensive response to larval infestation
Authors: Stanley Robert K. , Carey David W. , Mason Mary E. , Doran Aletta , Wolf Julia , Otoo Kingsley Owusu , Poland Therese M. , Koch Jennifer L. , Jones A. Daniel , Romero-Severson Jeanne 
Published: July 2023

IntroductionLarvae of the invasive emerald ash borer [EAB, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae)], kill over 99% of green ash (Fraxinus pennsylvanica Marshall) trees they infest, yet a small percentage of green ash (“lingering ash”) survive years of heavy EAB attack. In the face of an ongoing invasion that threatens multiple North American Fraxinus species with extinction, any evidence for reproducible defensive responses in the native species merits investigation.MethodsWe evaluated the capacity of three families of green ash F1 progeny to kill EAB larvae when challenged in greenhouse studies by infestation with a uniform density of EAB eggs followed by dissection 8 weeks post-infestation and comparison of the host metabolomic profiles.ResultsThe mean proportions of host-killed larvae in the two families of F1 progeny from lingering ash parents were significantly higher than that of host-killed larvae in the family of F1 progeny from susceptible ash parents (p &lt; 0.001). Untargeted metabolomics comparing F1 progeny in the quartile with the highest percent host-killed larvae (HHK) to F1 progeny in the quartile with the lowest percent host-killed larvae (LHK) and to the uninfested F1 progeny within each family revealed evidence for induced biochemical responses to EAB. Infested trees produced significantly higher levels of select secoiridoids than uninfested trees, and LHK progeny produced significantly higher levels of select secoiridoids than the HHK progeny. HHK progeny produced significantly higher abundances of three metabolites annotated as aromatic alkaloids than the LHK and uninfested individuals.DiscussionBased on these results, we hypothesize that green ash responds to EAB infestation. However, only certain trees have the genetic capacity to tailor a response that kills enough EAB larvae to prevent lethal damage to the vascular system. Rigorous tests of this hypothesis will require 15–20 years of additional crossing, phenotyping, and omics analyses. The results of this investigation will encourage the establishment and continuation of breeding programs that, in concert with biocontrol and management, could provide trees that slow, if not halt, the decimation of the Fraxinus gene pool. At the same time, ongoing work on host-insect interaction will contribute to our understanding of how forest trees recognize and defend themselves against phloem-feeding insects.
Identification of prior dengue-naïve Dengvaxia recipients with an increased risk for symptomatic dengue during fever surveillance in the Philippines
Authors: Dai Yu-Ching , Sy Ava Kristy , Jiz Mario , Tsai Jih-Jin , Bato Joan , Quinoñes Mary Ann , Reyes Mary Anne Joy , Wang Wei-Kung 
Published: July 2023

IntroductionDengue virus (DENV) is the leading cause of mosquito-borne viral diseases in humans. Dengvaxia, the first licensed dengue vaccine, is recommended for DENV-seropositive individuals aged 9–45 years. In the Philippines, Dengvaxia was administered to more than 830,000 children without prior serological testing in 2016–2017. Subsequently, it was revealed that DENV-seronegative children who received Dengvaxia developed severe disease following breakthrough DENV infection. As a result, thousands of children participating in the mass vaccination campaign were at higher risk of severe dengue disease. It is vital that an assay that identifies baseline DENV-naïve Dengvaxia recipients be developed and validated. This would permit more frequent and extensive assessments and timely treatment of breakthrough DENV infections.MethodsWe evaluated the performance of a candidate assay, the DENV1–4 nonstructural protein 1 (NS1) IgG enzyme-linked immunosorbent assay (ELISA), developed by the University of Hawaii (UH), using well-documented serum/plasma samples including those &gt;20 years post-DENV infection, and tested samples from 199 study participants including 100 Dengvaxia recipients from the fever surveillance programs in the Philippines.ResultsThe sensitivity and specificity of the assay were 96.6% and 99.4%, respectively, which are higher than those reported for pre-vaccination screening. A significantly higher rate of symptomatic breakthrough DENV infection was found among children that were DENV-naïve (10/23) than among those that were DENV-immune (7/53) when vaccinated with Dengvaxia (p=0.004, Fisher’s exact test), demonstrating the feasibility of the assay and algorithms in clinical practice.ConclusionThe UH DENV1–4 NS1 IgG ELISA can determine baseline DENV serostatus among Dengvaxia recipients not only during non-acute dengue but also during breakthrough DENV infection, and has implications for assessing the long-term safety and effectiveness of Dengvaxia in the post-licensure period.
Positive effects of two decades of passive ecological restoration in a historically polluted marine site
Authors: Fanelli Emanuela , Dell’Anno Antonio , Nepote Ettore , Martire Marco Lo , Musco Luigi , Bianchelli Silvia , Gambi Cristina , Falco Pierpaolo , Memmola Francesco , Coluccelli Alessandro , Meola Martina , Varrella Stefano , Danovaro Roberto , Corinaldesi Cinzia 
Published: July 2023

The Mediterranean Sea is one of the most exploited regions of the world’s oceans. Here industrial activities have determined either acute or long-term impacts on coastal marine ecosystems. In this study, we investigated macrofauna distribution and diversity, and food-web functioning in a coastal area of the Mediterranean Sea facing an industrial chemical plant abandoned in the ‘90s to assess benthic ecosystem health. This area has been identified as a Site of National Interest (SNI) since 2002 and has been closed to any human activity awaiting to be remediated according to national laws. Our results indicate that, two decades after the SNI declaration (a decade after the plant decommissioning), there is no longer any sign of the impact of historical contaminations on macrofauna and benthic food web functioning. Overall, all the thirty-six sites showed high/good ecological quality according to the score assigned by AMBI and M-AMBI indexes, reflecting the absence of chronic impacts. Our findings reveal, for the first time, the positive effects of passive restoration (i.e., unassisted, or spontaneous recovery following cessation of anthropogenic impacts) on historically impacted coastal ecosystems since their health conditions, in terms of both abiotic (environmental variables and contaminant concentration) and biotic (macrofauna diversity and community composition, and benthic food-web structure) factors, were indistinguishable from surrounding non-impacted areas. These findings also suggest that other effective area-based conservation measures (OECMs) could be useful not only for biodiversity conservation of vulnerable and priority habitats in larger ocean sectors but also to promote the passive recovery of historically contaminated ecosystems.
Comparative efficacies of various corticosteroids for preventing postextubation stridor and reintubation: a systematic review and network meta-analysis
Authors: Feng I-Jung , Lin Jia-Wei , Lai Chih-Cheng , Cheng Kuo-Chen , Chen Chin-Ming , Chao Chien-Ming , Wang Ying-Ting , Chiang Shyh-Ren , Liao Kuang-Ming 
Published: July 2023

ObjectivesWe assessed the efficacies of various corticosteroid treatments for preventing postexubation stridor and reintubation in mechanically ventilated adults with planned extubation.MethodsWe searched the Pubmed, Embase, the Cochrane databases and ClinicalTrial.gov registration for articles published through September 29, 2022. Only randomized controlled trials (RCTs) that compared the clinical efficacies of systemic corticosteroids and other therapeutics for preventing postextubation stridor and reintubation were included. The primary outcome was postextubation stridor and the secondary outcome was reintubation.ResultsThe 11 assessed RCTs reported 4 nodes: methylprednisolone, dexamethasone, hydrocortisone, and placebo, which yielded 3 possible pairs for comparing the risks of post extubation stridor and 3 possible pairs for comparing the risks of reintubation. The risk of postextubation stridor was significantly lower in dexamethasone- and methylprednisolone-treated patients than in placebo-treated patients (dexamethasone: OR = 0.39; 95% CI = 0.22–0.70; methylprednisolone: OR = 0.22; 95% CI = 0.11–0.41). The risk of postextubation stridor was significantly lower in methylprednisolone-treated patients than in hydrocortisone-treated: OR = 0.24; 95% CI = 0.08–0.67) and dexamethasone-treated patients: OR = 0.55; 95% CI = 0.24–1.26). The risk of reintubation was significantly lower in dexamethasone- and methylprednisolone-treated patients than in placebo-treated patients: (dexamethasone: OR = 0.34; 95% CI = 0.13–0.85; methylprednisolone: OR = 0.42; 95% CI = 0.25–0.70). Cluster analysis showed that dexamethasone- and methylprednisolone-treated patients had the lowest risks of stridor and reintubation. Subgroup analyses of patients with positive cuff-leak tests showed similar results.ConclusionsMethylprednisolone and dexamethasone were the most effective agents against postextubation stridor and reintubation.