bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between endoscopic pressure study integrated system (EPSIS) and high-resolution manometry
Authors: Fujiyoshi Yusuke , Inoue Haruhiro , Shimamura Yuto , Fujiyoshi Mary Raina Angeli , de Santiago Enrique Rodriguez , Nishikawa Yohei , Toshimori Akiko , Tanabe Mayo , Sumi Kazuya , Ono Masashi , Iwaya Yugo , Ikeda Haruo , Onimaru Manabu 
Published: June 2022

Abstract
Background and study aims The endoscopic pressure study integrated system (EPSIS), a novel diagnostic tool for gastroesophageal reflux disease (GERD), allows evaluation of the anti-reflux barrier using endoscopy by monitoring the intragastric pressure (IGP) during insufflation. In this study, we evaluated the association between EPSIS results and lower esophageal sphincter (LES) function measured by high-resolution manometry (HRM) to elucidate whether EPSIS can evaluate the LES function.
Patients and methods A retrospective, single-center study of patients with GERD symptoms who underwent endoscopy, pH-impedance monitoring, EPSIS, and HRM was conducted. The primary outcome was basal LES pressure and the secondary outcomes were end-respiratory LES pressure and integrated relaxation pressure (IRP). As EPSIS parameters, the following were measured: 1) pressure difference (mmHg), the difference between maximum and basal IGP; and 2) pressure gradient (mmHg/s), calculated by dividing pressure difference by the insufflating time. Pressure difference < 4.7 mmHg or pressure gradient < 0.07 mmHg/s was defined as an EPSIS GERD pattern.
Results Forty-seven patients (median age: 53 years, 37 female) were analyzed. Pressure difference and pressure gradient significantly correlated with basal LES pressure (ρ = 0.29; P = 0.04 and ρ = 0.29; P = 0.04). Patients with EPSIS GERD pattern showed significantly lower basal LES pressure [13.2 (4.8–26.6) vs 25.3 (10.4–66.7) mmHg, P = 0.002], lower end-respiratory LES pressure [8.5 (1.1–15.9) vs 15.5 (1.9–43.9) mmHg, P = 0.019] and lower IRP [5.9 (1.0–12.0) vs 9.8 (1.3–17.8) mmHg, P = 0.020].
Conclusions This study showed a close association between EPSIS results and LES pressures measured by HRM. This indicates that EPSIS can evaluate the LES function during endoscopy and endorse the role of EPSIS as a diagnostic tool for GERD.
Entwicklungen in der Diagnostik und Planung der Therapie bei der Apert-Hand
Authors: Piza-Katzer Hildegunde 
Published: June 2022

ZusammenfassungAuf die Notwendigkeit einer frühzeitigen Korrektur von Apert-Händen für die Gesamtentwicklung des Kindes wurde mehrfach bereits in der älteren Literatur hingewiesen. Dennoch bestehen weiterhin Unsicherheiten hinsichtlich des Zeitpunktes der ersten Operation und auch bezüglich deren Umfang. Erfolgten früher nach Abschluss der Fingertrennung keine regelmäßigen Kontrollen mehr, wissen wir heute, dass es im Laufe des Wachstums zu knöchernen Veränderungen an Apert-Händen kommt, die regelmäßige Kontrollen und ggf. Revisionsoperationen erfordern. Betroffene Eltern benötigen von Beginn an eine umfassende Aufklärung über ein klares und zeitlich effizientes Therapiekonzept. Die vorliegende Arbeit beschreibt unser aktuelles Therapiekonzept.
Der Apert-Fuß: Anatomische Veränderungen, Klassifikation und Überlegungen zur Operation
Authors: Piza-Katzer Hildegunde , Mandici Sandra , Ramach Wolfgang 
Published: June 2022

ZusammenfassungDiagnostik und Therapie des Apert-Fußes sind in der Literatur nur spärlich behandelt. Dieser Artikel beschreibt anatomische Veränderungen von 30 Apert-Füßen (15 Patienten). Anhand der Analyse von Röntgen- und CT-Bildern wurden 5 Schweregrade der Knochenveränderungen identifiziert und daran orientiert Therapieempfehlungen entwickelt.
Conception rate according to antral follicle count and oestrus expression in Nelore cows submitted to timed artificial insemination
Authors: Moraes Fábio Lucas Zito de , Bonato Denis Vinicius , Souza Ana Clara Canto , Morotti Fábio , Seneda Marcelo Marcondes 
Published: June 2022

Context Antral follicle count (AFC) has been related to bovine fertility and response to reproductive biotechnologies, but its relationship to oestrus expression during timed artificial insemination (TAI) is not known. Aims This study evaluated the relationship between the AFC and oestrus expression in regard to the conception rate in beef cows that received an ovulation synchronisation protocol for TAI. Methods Multiparous Nelore cows up to 40 days postpartum were evaluated by an ultrasound to determine the AFC, and were classified into low (≤15 follicles; n = 150), intermediate (≥19 and ≤26 follicles; n = 150) and high count (≥30 follicles; n = 150). AFC evaluation was performed on a random day of the oestrous cycle (Day 0). The animals received a conventional TAI protocol based on progesterone and oestradiol benzoate. On Day 8, the animals received cloprostenol, equine chorionic gonadotrophin and oestradiol cypionate, in addition to a painting in the sacrococcygeal region. On Day 10, TAI was performed, and oestrus expression was evaluated and classified as high, low or absent, according to the removal of paint. Pregnancy diagnosis was performed by ultrasound 30 days after TAI. The data were analysed using a generalised linear model and a binary logistic regression model (P < 0.05). Key results Regardless of AFC, a high proportion of cows showed high oestrus expression (low 61.3%; intermediate 67.3% and high 58.7%) at the end of the TAI protocol. The conception rate was influenced by AFC (low 69.3% vs high 56.7%; P = 0.04) and oestrus expression (high oestrus: 67.3% vs no oestrus: 45.4%; P = 0.003). In addition, an interaction (P = 0.008) between AFC and oestrus expression showed that low AFC cows and high oestrus expression had the highest conception rate to TAI. Conclusion AFC and oestrus expression classification influenced the conception rate of Nelore cows in the TAI programme. In addition, the interaction of AFC with oestrus expression revealed that the best conception rate was observed in females with low AFC that expressed high-intensity oestrus. Implications The associated assessment of AFC and oestrus expression represents a strategy to increase the conception rate in TAI programmes in cattle.
Multiplex Detection of Antibody Landscapes to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)/Influenza/Common Human Coronaviruses Following Vaccination or Infection With SARS-CoV-2 and Influenza
Authors: Li Zhu Nan , Liu Feng , Jefferson Stacie , Horner Lauren , Carney Paul , Johnson Michael D L , King Jennifer P , Martin Emily T , Zimmerman Richard K , Wernli Karen , Gaglani Manjusha , Thompson Mark , Flannery Brendan , Stevens James , Tumpey Terrence , Levine Min Z 
Published: June 2022

Abstract

Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses continue to co-circulate, representing 2 major public health threats from respiratory infections with similar clinical presentations. SARS-CoV-2 and influenza vaccines can also now be co-administered. However, data on antibody responses to SARS-CoV-2 and influenza coinfection and vaccine co-administration remain limited.

Methods
We developed a 41-plex antibody immunity assay that can simultaneously characterize antibody landscapes to SARS-CoV-2/influenza/common human coronaviruses. We analyzed sera from 840 individuals (11–93 years), including sera from reverse transcription–polymerase chain reaction (RT-PCR)–confirmed SARS-CoV-2–positive (n = 218) and –negative (n = 120) cases, paired sera from SARS-CoV-2 vaccination (n = 29) and infection (n = 11), and paired sera from influenza vaccination (n = 56) and RT-PCR–confirmed influenza infection (n = 158) cases. Last, we analyzed sera collected from 377 individuals who exhibited acute respiratory illness (ARI) in 2020.

Results
This 41-plex assay has high sensitivity and specificity in detecting SARS-CoV-2 infections. It differentiated SARS-CoV-2 vaccination (antibody responses only to spike protein) from infection (antibody responses to both spike and nucleoprotein). No cross-reactive antibodies were induced to SARS-CoV-2 from influenza vaccination and infection, and vice versa, suggesting no interaction between SARS-CoV-2 and influenza antibody responses. However, cross-reactive antibodies were detected between spike proteins of SARS-CoV-2 and common human coronaviruses that were removed by serum adsorption. Among 377 individuals who exhibited ARI in 2020, 129 were influenza positive; none had serological evidence of SARS-CoV-2/influenza coinfections.

Conclusions
Multiplex detection of antibody landscapes can provide in-depth analysis of the antibody protective immunity to SARS-CoV-2 in the context of other respiratory viruses, including influenza.
Morphometric, histological and immunohistochemical study of the His bundle in humans and other animal species
Authors: Gomez-Torres FA , Rios Navarro C , Ortega M , Bodi V , Ruiz-Sauri A 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (grant numbers PI20/00637 and CIBERCV16/11/00486) and Conselleria de Educación – Generalitat Valenciana (PROMETEO/2021/008).

Introduction
The His bundle is responsible for transmitting the electrical impulse from the atria to the ventricles where it connects with the Purkinje cells in both normal and abnormal hearts. The aim of this study was to perform a morphometric analysis of His bundle characteristics of in humans, dogs, horses and pigs and compare them in these studied species.

Methods
We analyzed five hearts of human male adults, five male pig hearts, five hearts from male horses and five hearts of male dogs. Histological sections of 5 μm thickness were obtained and stained with hematoxylin–eosin and Masson’s trichrome; the desmin and periodic acid–Schiff methods were also used for precise identification of cells.

Results
The His bundle was found to be longer in horses (2.85 ± 1.02 mm) and pigs (1.77 ± 0.9 mm) than in dogs (1.53 ± 0.8 mm) or humans, in which it was shortest (1.06 ± 0.6 mm). The area and diameters in His bundle cells, were significantly larger in pigs and horses than in humans (p &lt; 0.001) or dogs (p &lt; 0.001). We found two organizational patterns of His bundle components: group I, with large cells and a high amount of collagen fibers in ungulates (pigs and horses); and group II, with smaller cells and lower abundance of collagen fibers in humans and dogs.

Conclusions
Determining morphometrically cell size variations in the His bundle allows us not only to identify this bundle by histological or anatomical location but also to differentiate these cells from others such as nodal or Purkinje cells. Our analysis revealed that His bundle cells have discrete identities based on their morphometric and histological characteristics.
m6A modification regulates early human cardiomyocyte lineage specification
Authors: Spano G , De Majo F , Hegenbarth JC , Tiburcy M , Zimmermann WH , De Windt LJ 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 813716.

Background
RNA modifications affect gene expression through the regulation of RNA metabolism. N6-methyladenosine (m6A) is the most abundant post-transcriptional modification that occurs in RNAs. Its dynamic expression is regulated by the "writer complex" (methyltransferases) and "erasers" (demethylases) and affects numerous biological functions, including mammalian embryonic stem cell (ESC) fate specification. However, the role of m6A in human cardiomyocyte (CM) lineage specification remains unclear.

Purpose
In this study, we aim to investigate the impact of m6A modification on early human cardiomyocyte differentiation, following the dynamic expression of m6A modification of human induced pluripotent stem cells (hiPSC) into cardiomyocytes (hiPSC-CMs).

Methods
hiPSCs were differentiated into hiPSC-CMs by mesodermal induction, followed by inhibition of WNT-signaling. We collected hiPSC derivates at different stages of the differentiation protocol: hiPSCs, hiPSC-derived cardiac mesoderm cells, hiPSC-derived cardiomyocyte progenitors (hiPSC-CPCs), and mature hiPSC-CMs. Protein levels of m6A key regulators were analyzed. To systematically profile the expression of m6A modification, we subjected hiPSC derivates to m6A immunoprecipitation combined with deep sequencing (MeRIP-seq) and RNA-seq. Enrichment analyses of gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were conducted to elucidate the biological significance of differentially expressed and methylated genes.

Results
m6A distribution analysis on hiPSC derivates revealed a conserved pattern on a transcriptome-wide level: methylation sites are mainly located nearby the stop coding regions. However, we observed upregulated levels of writer proteins during the transition of hiPSC-derived cardiac mesoderm cells into hiPSC-CPCs. Interestingly, the dynamic changes in writer protein levels toward hiPSC-CPC transition were accompanied by a higher number of significantly upregulated and hyper-methylated mRNA transcripts. GO and KEGG analyses indicated hyper-methylated upregulated transcripts are enriched in muscle cell differentiation, cardiac physiology and calcium and MAPK signaling pathways regulating heart contraction.

Conclusion
For the first time, our study provides evidence that m6A modification is a mediator of early human cardiomyocyte differentiation. The role of specific writer regulators and individual m6A transcripts will be further investigated.
Transcriptomic analysis and comparative characterization of rat H9C2, human AC16 and murine HL-1 cardiac cell lines
Authors: Gulyas-Onodi Z , Visnovitz T , Koncz A , Varadi B , Agg B , Kiss B , Makkos A , Nagy NR , Toth VE , Leszek P , Gorbe A , Giricz Z , Buzas EI , Ferdinandy P , Varga ZV 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union's Horizon 2020 research and innovation programme
National Research, Development and Innovation Fund of Hungary

Background
Cardiac cell lines and primary cell cultures are widely used to model various cardiovascular diseases in vitro. Despite the increasing number of publications using these models, limitations of these cell lines are still undetermined.

Purpose
The aim of our study was to compare the most commonly used cardiac cell lines to primary cultures and to mature cardiac tissues by transcriptomic analysis and morphological characterization.

Methods
H9C2 (rat), AC16 (human) and HL-1 (mouse) cardiac cell lines were differentiated towards a phenotype more resembling cardiomyocytes, by methods most widely used in the literature, and cells were harvested at stages of proliferation and differentiation. Whole left ventricular tissue, neonatal primary cardiac myocytes isolated from mice and rats, or human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) were applied as references. Transcriptome analysis and immunocytochemical detection of cardiac structural proteins were performed on all cell models.

Results
RNA expression of cardiac markers (e.g. Tnnt2, Ryr2, Tnni3) was markedly lower in cell lines compared to primary cells or hiPSC-CM and adult tissue controls. Differentiation procedures induced a significant increase in cardiac- and decrease in embryonic markers in AC16 and H9C2 lines; however, the overall expression pattern of investigated genes in all cell lines showed significant differences in comparison to corresponding myocardium or primary cultures. Immunocytochemistry confirmed low expressions of structural protein alpha-actinin and troponin I in cell lines.

Conclusion
Expression patterns of cardiomyocyte markers and mRNA profile indicates low-to-moderate similarity of cell lines to primary cells/cardiac tissues regardless the differentiation protocol used. These limitations should be taken into account while choosing cells as in vitro platforms to model cardiomyocytes and cardiovascular diseases.
Endothelin-1 amplifies ventricular repolarization heterogeneities in chronic myocardial infarction pigs
Authors: Olivan-Viguera A , Perez-Martinez A , Pueyo E 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministerio de Ciencia e Innovación (Spain) Diputación General de Aragón

Introduction
Endothelin-1 (ET-1) is a vasoconstrictor peptide secreted by endothelial cells and cardiac myocytes and fibroblasts. It is involved in oxidative stress, apoptosis regulation and ventricular remodeling processes associated with heart failure and ischemic cardiomyopathy, including myocardial hypertrophy, fibrosis and impaired conduction. ET-1 has been shown to influence cardiac electrophysiology by modulation of calcium and potassium currents and to contribute to arrhythmogenesis and sudden cardiac death.

Purpose
We aim to characterize the functional role of ET-1 in the electrophysiology of healed myocardial infarction (MI) by analysis of porcine ventricular slices as a highly representative model of ventricular tissue with preserved cellular cross-talks and architecture.

Methods
Domestic pigs (60–80 kg, n = 3) were infarcted by temporal occlusion of the left anterior descending coronary artery. 8-12 weeks after infarct induction, animals were cardioplegically arrested under deep anesthesia and sacrificed. All animal procedures conformed to the guidelines from Directive 2010/63/EU and were approved by local authorities.
350 µm-thick ventricular slices were produced from transmural tissue blocks of healed MI ventricles. Tissue blocks were taken from remote, adjacent and border zones of the infarct area. Slices were optically mapped within 8 hours after tissue collection to record transmembrane potential and intracellular calcium. Action Potential Duration (APD) and Calcium Transient Duration (CaTD) were measured at 80% repolarization for 0.5, 1 and 2 Hz pacing frequencies in the presence and absence of 100 nM ET-1.
The notation n/N is used to denote n tissue slices from N pigs.

Results
ET-1 prolonged the APD at all frequencies in remote zones, with mean prolongation percentages of 30.5%, 32%, 26.2% at 0.5, 1 and 2 Hz, respectively, n/N=7/3. However, only minor effects were observed in adjacent (mean APD prolongation of 3.3%, 4.9% and 10.7%, n/N=5/3) and border zones (7%, 4% and 3.6%, n/N=5/3).
ET-1 caused an increase in CaTD at 1 Hz in the three zones, with no significant regional differences in the amount of CaTD increase: mean prolongation of 14.1% (n/N=7/3) in the remote zone, 12.4 % (n/N=5/3) in the adjacent zone and 20.9% (n/N=4/3) in the border zone.

Conclusions
In chronic MI pigs, ET-1 induces strong APD and moderate CaTD prolongation of remote normal myocardium at low (0.5 Hz) to high (2 Hz) frequencies. The ET-1-induced effects on the AP of normal tissue, but not on CaT, are disrupted in the border zones of the infarct area and in its proximity. Our results point to ET-1 acting to enhance ventricular repolarization dispersion in chronic MI pigs, which might contribute to increased arrhythmia vulnerability.
Increased thermogenesis in hairless SHR is associated with enhanced myocardial connexin-43 signaling and suppression of pro-fibrotic signaling
Authors: Andelova K , Szeiffova Bacova B , Sykora M , Pavelka S , Pravenec M , Barancik M , Tribulova N 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic VEGA 2/0158/19, 2/0002/20 and Slovak Research and Development Agency APVV 18-0548,19-0317

Background
We have previously shown that downregulation of myocardial gap junction channel protein, connexin-43 (Cx43), and up-regulation of extracellular matrix (ECM) proteins in spontaneously hypertensive rats (SHR) hearts promote occurrence of lethal arrhythmia. Cold acclimation has a potential for reducing cardiovascular risk but there is a gap of knowledge concern the heart response to adaptive thermogenesis.

Purpose
To explore myocardial Cx43 and ECM proteins in genetically hairless strain of SHR, that represents rewarding model of increased adaptive thermogenesis.

Methods
Adult hairless males and females SHRM strain that harbors mutated desmoglein-4 gene and their wild type SHR were housed at standard 22 °C (that is below thermo-neutrality for these animals) and 12:12 hour light: dark cycle. WKY control rats were used as reference normotensive strain. Heart samples of the left ventricular tissue from euthanatized rats were used for the proteomics of Cx43, protein kinases, which phosphorylates Cx43, and for ECM markers TGF-β, SMAD2/3, MMP-2, collagen-1. Immunofluoresence detection of Cx43 was performed to examine its myocardial topology.

Key Results
Cx43 protein and its phosphorylatetd status was reduced in males and females SHR vs WKY rat hearts. In contrast, adaptive thermogenesis resulted in increased both parameters in SHRM regardless the sex. Moreover, pathological topology of Cx43 attributed to its enhanced localization at lateral sides of the cardiomyocytes in SHR was attenuated in SHRM. In addition, there were gentle differences in protein levels of PKA, PKG, PKCε, MAPK, Akt between SHR and SHRM. Protein level of TGF-β and SMAD2/3 were increased in SHR vs WKY rat hearts but decreased in SHRM unlike collagen-1 that was not altered in SHRM vs SHR.

Conclusion
Findings revealed beneficial up-regulation of myocardial Cx43 along with down-regulation of extracellular matrix proteins in response of hairless SHR to increased thermogenesis.