bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assisted reproductive technology outcomes and gene expression in unexplained infertility patients
Authors: Vaigauskaitė-Mažeikienė Brigita , Baušytė Raminta , Valatkaitė Elvina , Maželytė Rūta , Kazėnaitė Edita , Ramašauskaitė Diana , Navakauskienė Rūta 
Published: July 2023

Background: Unexplained infertility (UI) can be a frustrating and challenging diagnosis for doctors and couples as it can be difficult to understand why they are unable to conceive despite increasing diagnostic tools. Assisted reproductive technology (ART) procedures have been successfully applied to many couples aiming to overcome UI. However, they can be not only expensive but also require multiple cycles to achieve a successful pregnancy. The endometrium and the follicular fluid have been investigated as target tissues not only to determine the cause of UI but also to increase conception rates.Results: In this study, we analyzed the outcomes of ART in 223 UI couples and gene expression associated with DNA modification, cell death, immune response and senescence (TET1, TET2, BCL2, BAK1, HMGA2, IL-6, IL-8) in infertile women’s endometrium and follicular fluid. We found significant differences in women who successfully got pregnant compared to women unable to conceive depending on age, duration of infertility, number of retrieved oocytes, zygotes, transferred embryos. Further, the expression of genes BAK1 (pro-apoptotic), TET2 (associated with epigenetic DNA modification) and IL-6 (associated with immune responses) were significantly higher in the endometrium of women who successfully got pregnant.Conclusion: Younger parental age couples showed higher ART success rates, shorter duration of infertility, higher number of retrieved oocytes, zygotes and transferred embryos. The gene expression analysis revealed significant changes in the endometrium depending on genes associated with cell death and immune response which were upregulated in females with diagnosed unexplained infertility.
Relating polar bears killed, human presence, and ice conditions in Svalbard 1987–2019
Authors: Vongraven D. , Amstrup S. C. , McDonald T. L. , Mitchell J. , Yoccoz N. G. 
Published: July 2023

Conflicts between humans and polar bears have been predicted to increase as polar bear prime habitat, sea ice, is decreasing. In Svalbard, a strict protection and control schemes have secured near complete records of bears killed and found dead since 1987. We analyzed the trend in the number of kills and related this to human visitation to the archipelago. We found a slight decrease in the number of kills in the period 1987-2019, and a decrease in per capita number of kills when monthly kills were compared to the monthly number of visitors disembarking in the main settlement. We then used a discrete choice resource selection model to assess whether polar bear kill events are related to attributes of the kill sites and environmental conditions at the time. We divided Svalbard in four sectors, North, East, South, and West, and monthly average ice cover was calculated in 25-km rings around Svalbard, rings that were further delineated by the four sectors. We found that the odds of a kill was greater along the shoreline, and that the odds would be reduced by 50% when moving only 900 m from the shoreline when all sectors were included. Distance from other covariates like settlements, trapper’s cabins, and landing sites for tourists did for the most part not have a significant impact on the odds of a kill. Sectorwise, ice cover had no significant impact on the odds for a kill. The decreasing trend in kills of polar bears might partly be explained by the success of strict protection and management regimes of Svalbard wilderness.
3D Virtual modelling, 3D printing and extended reality for planning of implant procedure of short-term and long-term mechanical circulatory support devices and heart transplantation
Authors: Stepanenko Alexander , Perez Laura Maroto , Ferre Jordi Candela , Ybarra Falcón Cristina , Pérez de la Sota Enrique , San Roman Jose Alberto , Redondo Diéguez Alfredo , Baladron Carlos 
Published: July 2023

IntroductionThe use of three-dimensional (3D) reconstruction and printing technology, together with extended reality applied to advanced heart failure adult patients with complex anatomy, is rapidly spreading in clinical practice. We report practical experience with application to acute and chronic heart failure: planning and performing mechanical circulatory device insertion or heart transplantation.MethodsFrom November 2019 until February 2022, 53 3D virtual biomodels were produced for intervention planning (using Virtual/Augmented Reality and/or 3D printing), following a specific segmentation and preprocessing workflow for biomodelling, in patients with advanced heart failure due to structural heart disease or cardiomyopathies. Four of those patients were complex cases requiring mechanical circulatory support implant procedures in our center.ResultsOne short-term and three long-term ventricular assist device system were successfully clinically implanted after application of this technique. In other two cases with extremely high procedural risk, visualized after application of this multimodality imaging, heart transplantation was elected.Conclusion3D printing based planning and virtual procedure simulation, are of great importance to select appropriate candidates for mechanical circulatory support in case of complex patient anatomy and may help to diminish periprocedural complications. Extended reality represents a perspective tool in planification of complex surgical procedures or ventricular assist device insertion in this setting.
Integrative single-cell analysis of cardiac and pulmonary sarcoidosis using publicly available cardiac and bronchoalveolar lavage fluid sequencing datasets
Authors: Daoud Abdel , Lema Diego A. , Won Taejoon , Čiháková Daniela 
Published: July 2023

IntroductionCardiac presentation of autoimmune sarcoidosis, known as cardiac sarcoidosis (CS), is a poorly understood disease with high mortality and low diagnosis rate. While CS is an immunological syndrome, little is known about how cardiac parenchymal and stromal cells mediate its pathogenesis. Moreover, while most current sarcoidosis research is based on research in pulmonary sarcoidosis (PS), it remains unclear how much both presentations of sarcoidosis overlap. To tackle these concerns, we leveraged publicly available sarcoidosis transcriptomic datasets.MethodsTwo publicly available bronchoalveolar lavage single-cell RNA sequencing datasets were integrated to analyze PS relative to control. Additionally, two publicly available cardiac single-nucleus RNA sequencing datasets were integrated to analyze CS relative to control. Following integration, we ran cell-cell communication, transcription factor, and differential expression analyses on parenchymal, stromal, and immune subsets identified in our analysis.ResultsOur analysis revealed that there was an expansion of stromal and immune cells in PS and CS. We also observed upregulation of Th17.1 and attenuated activation transcriptional profiles in the immune cells of CS and PS relative to control. Additionally, we found upregulation of pro-inflammatory and pro-fibrotic transcriptional profiles in the cardiac stromal cells of CS relative to control. We also found that cardiomyocytes exhibited upregulated cardiac stress and proliferation transcriptional profiles in CS relative to control.ConclusionsOur integrative transcriptomic analysis shows that despite tissue-specific differences, there are shared transcriptional trends between CS and PS. It also shows that stromal and parenchymal populations exhibit transcriptional trends that could explain their pathogenic role in CS.
Interannual and decadal variabilities of phytoplankton community in the Bering Sea and the Arctic Ocean: a case study of relationship with ENSO and Arctic Oscillation abnormity
Authors: Liu Qian , Yang Dan , Zhang Haisheng , Lu Bing 
Published: July 2023

We used molecular biomarkers (brassicasterol, dinosterol and C37 alkenones) measured from the surface sediments of the Bering Sea, the Chukchi Sea and the western Arctic Ocean in years of 1999 and 2010 to represent the groups of phytoplankton (diatoms, dinoflagellates and coccolithophores) and reconstruct the phytoplankton composition structure and biomass. The distribution of concentrations of three biomarkers were compatible to previous studies on measured phytoplankton, which showed that the phytoplankton biomass was most abundant in the Chukchi Sea, followed by the Bering Sea and the western Arctic Ocean, and diatoms were the dominant group. It suggests that molecular biomarkers are the suitable indicators of phytoplankton composition, structure and abundance. A record of biomarkers in a sediment core (NB01) collected at the Bering Sea in 2010 presented that the biomass of three phytoplankton groups increased in past 107 years, and their variation patterns were consistent. The synchronous increase of concentrations of phytoplankton biomarkers and cholesterol, a proxy of zooplankton biomass, implied that the primary production increased intensely in the last hundreds of years, corresponding to the trend of sea-ice melting as a result of global warming. Moreover, our results suggested that the combined effect of the anormal interannual changes of the El Niño-Southern Oscillation (ENSO) and the Arctic Oscillations (AO) played a key role in regulating the interannual and decadal variations of phytoplankton biomass and community composition, giving us an insight into the impact of atmospheric circulation on phytoplankton production and carbon flux in the Arctic seas.
How to promote preservice teachers’ reflections through critical incident training
Authors: Anselmann Veronika 
Published: July 2023

IntroductionThis study with a pre-post design reports the results of training developed from the framework of reflective practice and the critical incident technique (CIT) for teacher education.MethodsFifty-three preservice teachers participated in either online or face-to-face training, with the aim of determining if the training sufficiently improved their reflection abilities. To this purpose, an online questionnaire with validated scales on educational satisfaction, reflection abilities, and learning logs were used. The data were analyzed using descriptive statistical analysis and t-tests, as well as qualitative data analysis.ResultsThe results show that the students significantly improved their teaching reflection abilities after participating in the training.DiscussionGiving preservice teachers the opportunity to reflect on their own experiences is thus an appropriate way to foster their reflection abilities.
The proteome and phosphoproteome of circulating extracellular vesicle-enriched preparations are associated with characteristic clinical features in type 1 diabetes
Authors: Casu Anna , Nunez Lopez Yury O. , Yu Gongxin , Clifford Christopher , Bilal Anika , Petrilli Alejandra M. , Cornnell Heather , Carnero Elvis Alvarez , Bhatheja Ananya , Corbin Karen D. , Iliuk Anton , Maahs David M. , Pratley Richard E. 
Published: July 2023

IntroductionThere are no validated clinical or laboratory biomarkers to identify and differentiate endotypes of type 1 diabetes (T1D) or the risk of progression to chronic complications. Extracellular vesicles (EVs) have been studied as biomarkers in several different disease states but have not been well studied in T1D.MethodsAs the initial step towards circulating biomarker identification in T1D, this pilot study aimed to provide an initial characterization of the proteomic and phosphoproteomic landscape of circulating EV-enriched preparations in participants with established T1D (N=10) and healthy normal volunteers (Controls) (N=7) (NCT03379792) carefully matched by age, race/ethnicity, sex, and BMI. EV-enriched preparations were obtained using EVtrap® technology. Proteins were identified and quantified by LC-MS analysis. Differential abundance and coexpression network (WGCNA), and pathway enrichment analyses were implemented.ResultsThe detected proteins and phosphoproteins were enriched (75%) in exosomal proteins cataloged in the ExoCarta database. A total of 181 proteins and 8 phosphoproteins were differentially abundant in participants with T1D compared to controls, including some well-known EVproteins (i.e., CD63, RAB14, BSG, LAMP2, and EZR). Enrichment analyses of differentially abundant proteins and phosphoproteins of EV-enriched preparations identified associations with neutrophil, platelet, and immune response functions, as well as prion protein aggregation. Downregulated proteins were involved in MHC class II signaling and the regulation of monocyte differentiation. Potential key roles in T1D for C1q, plasminogen, IL6ST, CD40, HLA-DQB1, HLA-DRB1, CD74, NUCB1, and SAP, are highlighted. Remarkably, WGCNA uncovered two protein modules significantly associated with pancreas size, which may be implicated in the pathogenesis of T1D. Similarly, these modules showed significant enrichment for membrane compartments, processes associated with inflammation and the immune response, and regulation of viral processes, among others.DiscussionThis study demonstrates the potential of proteomic and phosphoproteomic signatures of EV-enriched preparations to provide insight into the pathobiology of T1D. The WGCNA analysis could be a powerful tool to discriminate signatures associated with different pathobiological components of the disease.
Characterization of the TRPV6 calcium channel-specific phenotype by RNA-seq in castration-resistant human prostate cancer cells
Authors: Cordier Clément , Haustrate Aurélien , Prevarskaya Natalia , Lehen’kyi V’yacheslav 
Published: July 2023

Background: Transient receptor potential vanilloid subfamily member 6 (TRPV6), a highly calcium-selective channel, has been shown to play a significant role in calcium homeostasis and to participate both in vitro and in vivo in growth, cell survival, and drug resistance of prostate cancer. Its role and the corresponding calcium-dependent pathways were mainly studied in hormone-dependent human prostate cancer cell lines, often used as a model of early-stage prostate cancers. The goal of the present study was to describe the TRPV6-specific phenotype and signaling pathways it is involved in, using castration-resistant prostate cancer cell lines.Methods: RNA sequencing (RNA-seq) was used to study the gene expression impacted by TRPV6 using PC3Mtrpv6−/−versus PC3Mtrpv6+/+ and its derivative PC3M-luc-C6trpv6+/+ cell line in its native and TRPV6 overexpressed form. In addition to the whole-cell RNA sequencing, immunoblotting, quantitative PCR, and calcium imaging were used to validate trpv6 gene status and functional consequences, in both trpv6-/- and TRPV6 overexpression cell lines.Results:trpv6-/- status was validated using both immunoblotting and quantitative PCR, and the functional consequences of either trpv6 gene deletion or TRPV6 overexpression were shown using calcium imaging. RNA-seq analysis demonstrated that the calcium channel TRPV6, being a crucial player of calcium signaling, significantly impacts the expression of genes involved in cancer progression, such as cell cycle regulation, chemotaxis, migration, invasion, apoptosis, ferroptosis as well as drug resistance, and extracellular matrix (ECM) re-organization.Conclusion: Our data suggest that the trpv6 gene is involved in and regulates multiple pathways related to tumor progression and drug resistance in castration-resistant prostate cancer cells.
Functional reprogramming of peripheral blood monocytes by soluble mediators in patients with pancreatic cancer and intraductal papillary mucinous neoplasms
Authors: Eckhoff Austin M. , Brown Michael C. , Landa Karenia , Naqvi Ibtehaj , Holl Eda K. , Boczkowski David , Fletcher Ashley , Rhodin Kristen E. , Giang Minh Huy , Sullenger Bruce , Beasley Georgia M. , Allen Peter J. , Nair Smita K. 
Published: July 2023

BackgroundMonocytes and monocyte-derived tumor infiltrating cells have been implicated in the immunosuppression and immune evasion associated with pancreatic adenocarcinoma (PDAC). Yet, precisely how monocytes in the periphery and tumor microenvironment in patients with intraductal papillary mucinous neoplasm (IPMN), a precursor lesion to PDAC, change during disease progression has not been defined. Here we functionally profiled the peripheral immune system and characterized the tumor microenvironment of patients with both IPMN and PDAC. We also tested if sera from patients with IPMN and PDAC functionally reprogram monocytes relative to that of healthy donors.MethodsPancreatic tissue and peripheral blood were collected at the time of resection from 16 patients with IPMN and 32 patients with PDAC. Peripheral blood and pancreatic tissue/tumor were immunophenotyped using flow cytometry. Whole blood was plated and incubated with R848 (a TLR 7/8 agonist) or LPS (a TLR4 agonist) for 6 hours and TNF expression in monocytes was measured by flow cytometry to measure monocyte activation. To test if TLR sensitivity is determined by factors in patient sera, we preconditioned healthy donor monocytes in serum from PDAC (n=23), IPMN (n=15), or age-matched healthy donors (n=10) followed by in vitro stimulation with R848 or LPS and multiplex cytokine measurements in the supernatant.ResultsTNF expression in R848-stimulated peripheral blood monocytes was higher in patients with low grade vs high grade IPMN (65% vs 32%, p = 0.03) and stage 1 vs stage 2/3 PDAC (58% vs 42%, p = 0.03), this was not observed after LPS stimulation. TLR activation correlated with increasing grade of dysplasia from low grade IPMN to high grade IPMN. Serum from patients with IPMN and PDAC recapitulated suppression of TNF induction after R848 stimulation in naïve, healthy donor monocytes.ConclusionPeripheral blood monocyte TNF secretion inversely correlates with the degree of dysplasia in IPMN and cancer stage in PDAC, suggesting innate immune reprogramming as IPMNs progress to invasive disease. These effects are, at least in part, mediated by soluble mediators in sera.
Chitinase-3-like 1 regulates TH2 cells, TFH cells and IgE responses to helminth infection
Authors: Curtiss Miranda L. , Rosenberg Alexander F. , Scharer Christopher D. , Mousseau Betty , Benavides Natalia A. Ballesteros , Bradley John E. , León Beatriz , Steele Chad , Randall Troy D. , Lund Frances E. 
Published: July 2023

IntroductionData from patient cohorts and mouse models of atopic dermatitis, food allergy and asthma strongly support a role for chitinase-3-like-1 protein (CHI3L1) in allergic disease.MethodsTo address whether Chi3l1 also contributes to TH2 responses following nematode infection, we infected Chi3l1-/- mice with Heligmosomoides polygyrus (Hp) and analyzed T cell responses.ResultsAs anticipated, we observed impaired TH2 responses in Hp-infected Chi3l1-/- mice. However, we also found that T cell intrinsic expression of Chi3l1 was required for ICOS upregulation following activation of naïve CD4 T cells and was necessary for the development of the IL-4+ TFH subset, which supports germinal center B cell reactions and IgE responses. We also observed roles for Chi3l1 in TFH, germinal center B cell, and IgE responses to alum-adjuvanted vaccination. While Chi3l1 was critical for IgE humoral responses it was not required for vaccine or infection-induced IgG1 responses.DiscussionThese results suggest that Chi3l1 modulates IgE responses, which are known to be highly dependent on IL-4-producing TFH cells.
The landscape of the immunoglobulin repertoire in endemic pemphigus foliaceus
Authors: Calonga-Solís Verónica , Olbrich Michael , Ott Fabian , Adelman Cipolla Gabriel , Malheiros Danielle , Künstner Axel , Farias Ticiana D.J. , Camargo Carolina M. , Petzl-Erler Maria Luiza , Busch Hauke , Fähnrich Anke , Augusto Danillo G. 
Published: July 2023

IntroductionPrimarily driven by autoreactive B cells, pemphigus foliaceus (PF) is an uncommon autoimmune blistering skin disease of sporadic occurrence worldwide. However, PF reaches a prevalence of 3% in the endemic areas of Brazil, the highest ever registered for any autoimmune disease, which indicates environmental factors influencing the immune response in susceptible individuals. We aimed to provide insights into the immune repertoire of patients with PF living in the endemic region of the disease, compared to healthy individuals from the endemic region and a non-endemic area.MethodsWe characterized the B-cell repertoire in i) nontreated patients (n=5); ii) patients under immunosuppressive treatment (n=5); iii) patients in remission without treatment (n=6); and two control groups iv) from the endemic (n=6) and v) non-endemic areas in Brazil (n=4). We used total RNA extracted from peripheral blood mononuclear cells and performed a comprehensive characterization of the variable region of immunoglobulin heavy chain (IGH) in IgG and IgM using next-generation sequencing.ResultsCompared to individuals from a different area, we observed remarkably lower clonotype diversity in the B-cell immune repertoire of patients and controls from the endemic area (p &lt; 0.02), suggesting that the immune repertoire in the endemic area is under geographically specific and intense environmental pressure. Moreover, we observed longer CDR3 sequences in patients, and we identified differential disease-specific usage of IGHV segments, including increased IGHV3-30 and decreased IGHV3-23 in patients with active disease (p &lt; 0.04). Finally, our robust network analysis discovered clusters of CDR3 sequences uniquely observed in patients with PF.DiscussionOur results indicate that environmental factors, in addition to disease state, impact the characteristics of the repertoire. Our findings can be applied to further investigation of the environmental factors that trigger pemphigus and expand the knowledge for identifying new targeted and more effective therapies.
Associations of complete blood cell count-derived inflammatory biomarkers with asthma and mortality in adults: a population-based study
Authors: Ke Junhua , Qiu Fushan , Fan Wenxi , Wei Songqing 
Published: July 2023

ObjectiveThis study aims to assess the associations of complete blood cell count (CBC)-derived inflammatory biomarkers with the prevalence of asthma and mortality.MethodsData was collected from the 1999-2018 National Health and Nutrition Examination Survey (NHANES). Mortality was identified using the National Death Index until December 31, 2019. The study analyzed the relationship between CBC-derived inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic inflammatory response index (SIRI), and systemic immune-inflammation index (SII), and the prevalence of asthma using multiple logistic regressions. To assess the significance of CBC-derived inflammatory biomarkers in predicting all-cause and respiratory disease mortality in asthma patients, Cox proportional regressions and the random survival forest (RSF) analysis were utilized.ResultsA total of 48,305 participants were included, with a mean age of 47.27 ± 0.18 years and 49.44% male. Among them, 6,403 participants had asthma, with a prevalence of 13.28%. The all-cause and respiratory disease deaths at a median follow-up of 8.2 (4.5, 12.8) years were 929 and 137 respectively. After adjusting for confounders, the prevalence of asthma was found to be positively associated with NLR, PLR, MLR, SIRI and SII. Compared to the lowest quartile, the highest quartile of NLR (HR=1.765 [1.378-2.262]), MLR (HR=1.717 [1.316-2.241]), SIRI (HR=1.796 [1.353-2.383]) and SII (HR=1.432 [1.141-1.797]) were associated with an increased risk of all-cause mortality. These associations were more pronounced in respiratory disease mortality of asthma patients. RSF analysis showed that MLR had the highest predictive value for all-cause and respiratory disease mortality in adults with asthma. The sensitivity analysis demonstrated the stability of our results.ConclusionThe findings suggest that CBC-derived inflammatory biomarkers are associated with a higher risk of all-cause and respiratory disease mortality in adults with asthma.