bluuebunny/crossref_metadata_2025 huggingface dataset:
No Reading Aloud! Sound and Silence in Plato’s Socrates and Derrida’s Plato
Authors: Naas Michael
Published: December 2022

In ‘Reading and Its Discontents’, Anne Emmanuelle Berger makes a plea for the specificity of reading literature. Unlike other kinds of reading, the reading of literature has the unique ability to ‘keep the wound open’. As such, it can never be reduced, as some have recently tried, to just another form of culture production or to some politically motivated pedagogical therapeutics. It is also a type of reading, this essay will argue, that cannot be reduced to the kind of silent reading that, as Derrida demonstrated in ‘Plato’s Pharmacy’, has been the model and telos of reading since Plato. After a brief look at the controversy surrounding the history of silent reading, this essay looks at the question of reading in Plato and, especially, at the surprising number of references in the dialogues to Socrates as a reader. It then turns to Derrida’s reading of Plato in ‘Plato’s Pharmacy’, first to Derrida’s critique of the Platonic model of reading and writing in the dialogues and then to the deployment of a new kind of philosophical reading and writing in Derrida’s own work, a reading that, as Berger herself suggests, is always also a writing, a reading that is itself then always double, at once silent and aloud.
Effectiveness of the feed additive "AspiSorb" in the pathology of the digestive system in pigs
Authors: VELIKANOV Vitaliy
Published: December 2022

The article presents the results of the scientific experiment on the study of a new sorbent feed additive "AspiSorb", the use of which will increase the effectiveness of veterinary measures in the prevention and treatment of the pigs’ digestive system diseases. It is shown that "AspiSorb" does not have chronic toxicity. It does not adversely affect the condition of healthy piglets, and the quality and safety of animal slaughter products. It helps to reduce the level of endogenous intoxication of the body and the rapid disappearance of signs of exsicosis, which is confirmed by the normalization of general analysis of blood, as well as the activity of ASAT, AST, alkaline phosphatase, the concentration of cholesterol, bilirubin, glucose and albumin. The inclusion of "AspiSorb" sorbent in the complex scheme for the prevention of gastroenteritis and toxic hepatodystrophy in piglets helps to reduce the incidence and reduce the severity of the disease.
Breeding achievements of the SFNCA RAS for feed production in Siberia
Authors: Polyudina Revmira , Grishin Vasiliy , Potapov Dmitriy
Published: December 2022

Over the past 5 years, 16 varieties have been created and included in the state register of breeding achievements of the Russian Federation and the Republic of Kazakhstan in the SFNCA RAS: meadow clover — Meteor, Prima; Sudanese grass — Dostyk 15, Karagandinskaya, Nika; spring rapeseed — SibNIIK 21, SibNIIK 32; oilseed radish — Sibiryachka; soy — SibNIIK 9, Gorinskaya; sandy sainfoin — Mikhailovsky 5, Mikhailovsky 10; bromus inermis — Flagman. 14 varieties of agricultural crops are evaluated at the state variety testing of the Russian Federation.
Yield of sugar corn depending on sowing time
Authors: KALAShNIKOV Maksim , KOCAREVA Nadezhda
Published: December 2022

The results of cultivation of sugar corn in the agricultural enterprise CJSC Pobeda of the Belgorod district of the Belgorod region are presented. As a result of the work, it was found that the yield of sweet corn depends on the timing of sowing. The yield of cobs and grains of corn of the main hybrid Royalty F1, cultivated on the farm, increased at the time of sowing, starting from the second decade of May, from 16.26 t/ha to 23.38 t/ha. The replacement of the main hybrid Royalty F1 with new hybrids led to a loss in yield of both cobs and grain yield of sugar corn for all sowing dates. According to the yield of grain from one cob, no definite dependence on the timing of sowing was noted.
Combined clover varieties of Russia and Belarus created under the TOS «Clever» program
Authors: Bushueva Vera Ivanovna , KOVALEVSKAYa Liliya , AVRAMENKO Marina , LYuBEZNAYa Margarita , Novoselov Mikhail
Published: December 2022

The article presents the results of selection of red clover in the EE BSAA under the program of TOS "Clover". The characteristics of the source material and methods for creating four varieties of red clover jointly bred by the EE BSAA and the Federal Williams fodder and agroecology research center. Directions and methods of further selection are demonstrated. The results of the assessment of the created varieties according to economically useful traits and properties in competitive and state variety trials in comparison with control varieties are presented. In total, four varieties of red clover of joint breeding were created, of which Sozh is late-ripening, TOS-870 is medium-late-ripening, GPTT-early and Verbush are early-ripening. Of all the varieties, GPTT-early turned out to be the most productive, which has been included in the state register of varieties of the Republic of Belarus since 2017 and approved for use in production conditions throughout the country. By the decision of the state inspectorate for the testing and protection of plant varieties, it has been approved since 2018 as a control in the state test of red clover being the best zoned variety. To create new varieties, the methods of chemical mutagenesis (phosphemid) and polyploidy (colchicine) are used in the EE BSAA). The created new source material is being evaluated in the breeding process nurseries.
Handling multiple levels in agent-based models of complex socio-environmental systems: A comprehensive review
Authors: Brugière Arthur , Nguyen-Ngoc Doanh , Drogoul Alexis
Published: December 2022

Agent-based modeling (ABM) has been successfully used, since its emergence in the 1990s, to model and simulate the dynamics at work in complex socio-environmental systems, in many domains and applications where interactions between people and their environments give rise to emergent phenomena that are difficult to study otherwise (urban planning, land-use change, adaptation to environmental changes, biodiversity protection in socio-ecosystems, environmental pollution control, etc.). The inclusion of multiple levels of analysis, abstraction, and representation in these models, however, is much more recent and is still the subject of many proposals and discussions within a relatively informal field, Multilevel Agent-Based Modeling (ML-ABM), which is most often presented as an approach that extends the classical ABM paradigm to include multilevel concepts. Over the past decade, ML-ABM has been increasingly adopted and explored by researchers as an effective paradigm for framing and defining the mechanisms underlying multilevel dynamics. However, due to the youth of the field, no single definition, methodology, or tool unifies studies in this rapidly expanding area. This review will begin with an introduction to socio-environmental systems (SES) and the challenges that modeling approaches face in representing them properly, especially regarding the complexity of human behaviors and organizations. ABM presents opportunities for modeling SESs with respect to these challenges, including the simulation of individual and social behavior and their ability to provide a descriptive and generative representation of the simulated system. However, ABM is limited in its ability to represent levels and scales, as these concepts are absent from the classical ABM metamodel. A complete review of the ML-ABM literature will be carried out, structured around a continuum that emerged during the review: that of the distribution of behaviors (and thus, from a software engineering perspective, of control) across the levels, from approaches that allow only one level to be active at a time, to approaches that rely on simultaneous activity and feedback loops between several levels. Different design choices will, thus, be presented to meet the different needs of multi-level representation, focusing on the interest on modelers and the strengths and limitations of each. In particular, we will highlight a limitation shared by all the reviewed approaches, namely their inability to represent several parallel hierarchies of levels and their interactions, a capability that appears more and more crucial to finely represent social behaviors in SES. A new perspective on the interest that the AGR approach could represent to allow this representation of hierarchies allows us to conclude on the research perspectives are still open.
Novel axial compressive endoprosthesis ACE can enhance metaphyseal fixation and facilitate osseointegration: A biomechanical study
Authors: Huang Siyi , Ji Tao , Tang Xiaodong , Guo Wei
Published: December 2022

Background: Metaphyseal fixation for endoprosthetic reconstruction after bone tumor resection is difficult due to the short residual bone length and reverse funnel shape of the metaphysis. In the current study, 3D-printed axial compressive endoprosthesis (ACE) with a short stem and intramedullary axial compressive mechanism is proposed to improve metaphyseal fixation. The rationales of ACE are that 1) intramedullary axial compress enhances the stability of endoprosthesis and facilitates bone ingrowth at the osteotomy site; 2) 3D printed porous metallic surface at osteotomy surface and stem allows bone ingrowth to achieve osseointegration.

Methods: A biomechanical study was performed to explore the initial stability using Sawbones. A diaphysis and metaphyseal segmental defect were created and four fixation structures were simulated: 1) ACE; 2) ACE + lateral plate; 3) stem prosthesis + unilateral plate; 4) stem prosthesis + bilateral plates. Bending and torsional stiffness were determined with a material testing machine. The relationship between the torque of the compression nut and the axial compression force of the bone-implant surface was measured using a round gasket load sensor.

Results: ACE + lateral plate was the stiffest in the bending test (sagittal 324.3 ± 110.8 N/mm, coronal 307.7 ± 8.7 N/mm). ACE + lateral plate and stem prosthesis + bilateral plates had the highest torsional stiffness (10.9 ± 1.3 Nm/° and 10.7 ± 0.2 Nm/° respectively). The bending stiffness of ACE was equivalent to stem prosthesis + bilateral plates (sagittal 196 ± 10 N/mm vs. 200 ± 7 N/mm, coronal 197 ± 14 N/mm vs. 209 ± 3 N/mm), but the torsional stiffness of ACE was inferior to stem prosthesis + bilateral plates (6.1 ± 1.3 Nm/° vs. 10.7 ± 0.2 Nm/°). Stem prosthesis + unilateral plate was the least stiff both in bending and torsion. The relationship between torque (T/Nm) and axial pressure (F/N) was F = 233.5T.

Conclusion: The axial compressive design of ACE enhances primary stability and facilitates osseointegration, which provides an alternative option of metaphyseal fixation for endoprosthetic reconstruction.
DNA-enabled fluorescent-based nanosensors monitoring tumor-related RNA toward advanced cancer diagnosis: A review
Authors: Dong Fengqi , Yan Weizhen , Dong Wuqi , Shang Xiaofei , Xu Yanli , Liu Wei , Wu Yunkai , Wei Wenmei , Zhao Tingting
Published: December 2022

As a burgeoning non-invasive indicator for reproducible cancer diagnosis, tumor-related biomarkers have a wide range of applications in early cancer screening, efficacy monitoring, and prognosis predicting. Accurate and efficient biomarker determination, therefore, is of great importance to prevent cancer progression at an early stage, thus reducing the disease burden on the entire population, and facilitating advanced therapies for cancer. During the last few years, various DNA structure-based fluorescent probes have established a versatile platform for biological measurements, due to their inherent biocompatibility, excellent capacity to recognize nucleic and non-nucleic acid targets, obvious accessibility to synthesis as well as chemical modification, and the ease of interfacing with signal amplification protocols. After decades of research, DNA fluorescent probe technology for detecting tumor-related mRNAs has gradually grown to maturity, especially the advent of fluorescent nanoprobes has taken the process to a new level. Here, a systematic introduction to recent trends and advances focusing on various nanomaterials-related DNA fluorescent probes and the physicochemical properties of various involved nanomaterials (such as AuNP, GO, MnO2, SiO2, AuNR, etc.) are also presented in detail. Further, the strengths and weaknesses of existing probes were described and their progress in the detection of tumor-related mRNAs was illustrated. Also, the salient challenges were discussed later, with a few potential solutions.
Islet cilia and glucose homeostasis
Authors: Melena Isabella , Hughes Jing W.
Published: December 2022

Diabetes is a growing pandemic affecting over ten percent of the U.S. population. Individuals with all types of diabetes exhibit glucose dysregulation due to altered function and coordination of pancreatic islets. Within the critical intercellular space in pancreatic islets, the primary cilium emerges as an important physical structure mediating cell-cell crosstalk and signal transduction. Many events leading to hormone secretion, including GPCR and second-messenger signaling, are spatiotemporally regulated at the level of the cilium. In this review, we summarize current knowledge of cilia action in islet hormone regulation and glucose homeostasis, focusing on newly implicated ciliary pathways that regulate insulin exocytosis and intercellular communication. We present evidence of key signaling proteins on islet cilia and discuss ways in which cilia might functionally connect islet endocrine cells with the non-endocrine compartments. These discussions aim to stimulate conversations regarding the extent of cilia-controlled glucose homeostasis in health and in metabolic diseases.
Mechano-biochemical marine stimulation of inversion, gastrulation, and endomesoderm specification in multicellular Eukaryota
Authors: Nguyen Ngoc Minh , Merle Tatiana , Broders-Bondon Florence , Brunet Anne-Christine , Battistella Aude , Land Emelie Britt Linnea , Sarron Florian , Jha Aditya , Gennisson Jean-Luc , Röttinger Eric , Fernández-Sánchez María Elena , Farge Emmanuel
Published: December 2022

The evolutionary emergence of the primitive gut in Metazoa is one of the decisive events that conditioned the major evolutionary transition, leading to the origin of animal development. It is thought to have been induced by the specification of the endomesoderm (EM) into the multicellular tissue and its invagination (i.e., gastrulation). However, the biochemical signals underlying the evolutionary emergence of EM specification and gastrulation remain unknown. Herein, we find that hydrodynamic mechanical strains, reminiscent of soft marine flow, trigger active tissue invagination/gastrulation or curvature reversal via a Myo-II-dependent mechanotransductive process in both the metazoan Nematostella vectensis (cnidaria) and the multicellular choanoflagellate Choanoeca flexa. In the latter, our data suggest that the curvature reversal is associated with a sensory-behavioral feeding response. Additionally, like in bilaterian animals, gastrulation in the cnidarian Nematostella vectensis is shown to participate in the biochemical specification of the EM through mechanical activation of the β-catenin pathway via the phosphorylation of Y654-βcatenin. Choanoflagellates are considered the closest living relative to metazoans, and the common ancestor of choanoflagellates and metazoans dates back at least 700 million years. Therefore, the present findings using these evolutionarily distant species suggest that the primitive emergence of the gut in Metazoa may have been initiated in response to marine mechanical stress already in multicellular pre-Metazoa. Then, the evolutionary transition may have been achieved by specifying the EM via a mechanosensitive Y654-βcatenin dependent mechanism, which appeared during early Metazoa evolution and is specifically conserved in all animals.
Doxorubicin aqueous systems at low concentrations: Interconnection between self-organization, fluorescent and physicochemical properties, and action on hydrobionts
Authors: Ryzhkina Irina , Murtazina Lyaisan , Kostina Larisa , Dokuchaeva Irina , Sergeeva Svetlana , Meleshenko Kristina , Shevelev Maxim , Petrov Andrew
Published: December 2022

Doxorubicin (Dox) is a highly effective cytostatic antibiotic that exhibits activity against a wide range of malignant neoplasms and is often used as the basis of various anti-tumor compositions. However, the use of Dox in therapeutic doses is associated with high systemic toxicity, which makes it urgent to find ways to reduce therapeutic concentrations, which is necessary primarily to minimize the side effects on the patient’s body, as well as to reduce the harmful effects on aquatic ecosystems, commonly polluted by toxic pharmaceuticals. Studying the self-organization, physicochemical and spectral patterns, and their relation to bioeffects of Dox solutions in the range of low concentrations can reveal useful insights into the unknown effects of Dox as a cytostatic and potential pollutant of ecosystems. The self-organization in solutions and on substrates, physicochemical and spectral properties, and action of Dox solutions on hydrobionts were studied in the range of calculated concentrations from 1·10−20 to 1·10−4 M by methods of dynamic and electrophoretic light scattering (DLS and ELS), scanning electron microscopy (SEM), scanning probe microscopy (SPM), fluorescence spectroscopy, UV absorption spectroscopy, conductometry, tensiometry, pH-metry. Certified techniques for monitoring the toxicity of natural water and wastewater were used to establish the interconnection between these phenomena. It was shown that aqueous solutions of Dox are dispersed systems which rearrange their dispersed phase measuring hundreds of nm in size (nanoassociates) at dilution, followed by concerted changes in nanoassociates’ parameters (size and ζ-potential) and properties of systems, as well as their bioassay results. SPM and SEM results confirm and complement the DLS and ELS data indicating the existence of nanoassociates in dilute Dox solutions.
Carbazole-based aggregation-induced phosphorescent emission-active gold(I) complexes with various phosphorescent mechanochromisms
Authors: Chen Zhao , Deng Xiao-Wen , Wang Xiao-Yan , Wang An-Qi , Luo Wen-Tao
Published: December 2022

A series of carbazole-containing gold(I) complexes modified with different substituents were successfully designed and synthesized, and their molecular structures were characterized by nuclear magnetic resonance spectroscopy and mass spectrometry. The aggregation-induced behaviors of these gold(I) complexes were studied by ultraviolet/visible and photoluminescence spectroscopy. Meanwhile, their mechanical force-responsive emissive properties were also investigated via solid-state photoluminescence spectroscopy. Interestingly, all these gold(I)-based luminogenic molecules were capable of exhibiting aggregation-induced phosphorescent emission phenomena. Furthermore, their solids of three gold(I) complexes displayed contrasting mechano-responsive phosphorescence features. More specifically, trifluoromethyl or methoxyl-substituted luminophores 1 and 3 demonstrated mechanochromic behaviors involving blue-shifted phosphorescence changes, and their mechanoluminochromic phenomena were reversible. However, the solid-state phosphorescence of phenyl-substituted luminophor 2 was not sensitive to external mechanical force.
Full-length transcriptome sequencing and comparative transcriptome analysis of Eriocheir sinensis in response to infection by the microsporidian Hepatospora eriocheir
Authors: Hou Libo , Wang Mengdi , Zhu Lei , Ning Mingxiao , Bi Jingxiu , Du Jie , Kong Xianghui , Gu Wei , Meng Qingguo
Published: December 2022

As a new generation of high-throughput sequencing technology, PacBio Iso-Seq technology (Iso-Seq) provides a better alternative sequencing method for the acquisition of full-length unigenes. In this study, a total of 22.27 gigabyte (Gb) subread bases and 128,614 non-redundant unigenes (mean length: 2,324 bp) were obtained from six main tissues of Eriocheir sinensis including the heart, nerve, intestine, muscle, gills and hepatopancreas. In addition, 74,732 unigenes were mapped to at least one of the following databases: Non-Redundant Protein Sequence Database (NR), Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG), KEGG Orthology (KO) and Protein family (Pfam). In addition, 6696 transcription factors (TFs), 28,458 long non-coding RNAs (lncRNAs) and 94,230 mRNA-miRNA pairs were identified. Hepatospora eriocheir is the primary pathogen of E. sinensis and can cause hepatopancreatic necrosis disease (HPND); the intestine is the main target tissue. Here, we attempted to identify the key genes related to H. eriocheir infection in the intestines of E. sinensis. By combining Iso-Seq and Illumina RNA-seq analysis, we identified a total of 12,708 differentially expressed unigenes (DEUs; 6,696 upregulated and 6,012 downregulated) in the crab intestine following infection with H. eriocheir. Based on the biological analysis of these DEUs, several key processes were identified, including energy metabolism-related pathways, cell apoptosis and innate immune-related pathways. Twelve selected genes from these DEUs were subsequently verified by quantitative real-time PCR (qRT-PCR) analysis. Our findings enhance our understanding of the E. sinensis transcriptome and the specific association between E. sinensis and H. eriocheir infection.
Transcriptome and proteome profiling of activated cardiac fibroblasts supports target prioritization in cardiac fibrosis
Authors: Moita Maria Raquel , Silva Marta M. , Diniz Cláudia , Serra Margarida , Hoet René M. , Barbas Ana , Simão Daniel
Published: December 2022

Background

Activated cardiac fibroblasts (CF) play a central role in cardiac fibrosis, a condition associated with most cardiovascular diseases. Conversion of quiescent into activated CF sustains heart integrity upon injury. However, permanence of CF in active state inflicts deleterious heart function effects. Mechanisms underlying this cell state conversion are still not fully disclosed, contributing to a limited target space and lack of effective anti-fibrotic therapies.

Materials and methods

To prioritize targets for drug development, we studied CF remodeling upon activation at transcriptomic and proteomic levels, using three different cell sources: primary adult CF (aHCF), primary fetal CF (fHCF), and induced pluripotent stem cells derived CF (hiPSC-CF).

Results

All cell sources showed a convergent response upon activation, with clear morphological and molecular remodeling associated with cell-cell and cell-matrix interactions. Quantitative proteomic analysis identified known cardiac fibrosis markers, such as FN1, CCN2, and Serpine1, but also revealed targets not previously associated with this condition, including MRC2, IGFBP7, and NT5DC2.

Conclusion

Exploring such targets to modulate CF phenotype represents a valuable opportunity for development of anti-fibrotic therapies. Also, we demonstrate that hiPSC-CF is a suitable cell source for preclinical research, displaying significantly lower basal activation level relative to primary cells, while being able to elicit a convergent response upon stimuli.
Skeletal muscle phenotypic switching in heart failure with preserved ejection fraction
Authors: Saw Eng Leng , Werner Louis Dominic , Zamani Payman , Chirinos Julio A. , Valero-Muñoz María , Sam Flora
Published: December 2022

Background

Skeletal muscle (SkM) phenotypic switching is associated with exercise intolerance in heart failure with preserved ejection fraction (HFpEF). Patients with HFpEF have decreased type-1 oxidative fibers and mitochondrial dysfunction, indicative of impaired oxidative capacity. The SAUNA (SAlty drinking water/Unilateral Nephrectomy/Aldosterone) mice are commonly used in HFpEF pre-clinical studies and demonstrate cardiac, lung, kidney, and white adipose tissue impairments. However, the SkM (specifically the oxidative-predominant, soleus muscle) has not been described in this preclinical HFpEF model. We sought to characterize the soleus skeletal muscle in the HFpEF SAUNA mice and investigate its translational potential.

Methods

HFpEF was induced in mice by uninephrectomy, d-aldosterone or saline (Sham) infusion by osmotic pump implantation, and 1% NaCl drinking water was given for 4 weeks. Mice were euthanized, and the oxidative-predominant soleus muscle was collected. We examined fiber composition, fiber cross-sectional area, capillary density, and fibrosis. Molecular analyses were also performed. To investigate the clinical relevance of this model, the oxidative-predominant, vastus lateralis muscle from patients with HFpEF was biopsied and examined for molecular changes in mitochondrial oxidative phosphorylation, vasculature, fibrosis, and inflammation.

Results

Histological analyses demonstrated a reduction in the abundance of oxidative fibers, type-2A fiber atrophy, decreased capillary density, and increased fibrotic area in the soleus muscle of HFpEF mice compared to Sham. Expression of targets of interest such as a reduction in mitochondrial oxidative-phosphorylation genes, increased VEGF-α and an elevated inflammatory response was also seen. The histological and molecular changes in HFpEF mice are consistent and comparable with changes seen in the oxidative-predominant SkM of patients with HFpEF.

Conclusion

The HFpEF SAUNA model recapitulates the SkM phenotypic switching seen in HFpEF patients. This model is suitable and relevant to study SkM phenotypic switching in HFpEF.
Malnutrition and infection lead to poor prognosis and heavy financial burden of patients with chronic heart failure
Authors: Jia Xu , Yu Xing-long , Lu Bin , Shang Yuan-yuan , Shen Long-fei , Li Yu-lin , Zhang Wei , Zhong Ming , Han Lu , Wang Zhi-Hao
Published: December 2022

Background

Chronic heart failure (CHF) is a major public health concern, as it is associated with poor prognosis and heavy financial burden. In recent years, there has been increasing interest in medications for CHF in China, but few studies pay attention to the effects of nutrition and infection.

Methods and results

This was a retrospective study collected patients with CHF admitted to the Department of Cardiology of Qilu Hospital of Shandong University from January 2017 to May 2018. Patients were classified according to the prognosis and the financial burden. Through comparison and regression analysis, we found that the factor associated with worse prognosis were decreased heart rate, albumin and prealbumin; β-blockers and mineralocorticoid receptor antagonism (MRA) were the factor improved the prognosis of patients with CHF; the factor overburdening financial condition were infection, decreased prealbumin, high Alanine aminotransferase (ALT), usage of recombinant human brain natriuretic peptide (rhBNP) and Levosimendan; aspirin and Sacubitril/Valsartan were the factor releasing financial burden of patients with CHF. Then, we grouped by Controlling Nutritional Status (CONUT) score, which enabled evaluation of the patient's protein reserve and immune defenses. Patients in the malnutrition group had higher infection ratios, longer hospital stays, and greater hospital expenses than the normal group. The improvement ratios of therapeutic outcomes in the moderate or severe malnutrition group were lower than in the normal and mild malnutrition group.

Conclusion

Malnutrition and infection caused poor prognosis and increased financial burden of patients with CHF. The high CONUT score indicated the CHF patient's unfavorable prognosis and heavy financial burden.
Mild COVID-19 induces early, quantifiable, persistent troponin I elevations in elder men
Authors: Bürgi Justus J. , Rösslein Matthias , Nolte Oliver , Wick Peter , Garcia Boy Regine , Stranders Siegfried , Dollenmaier Günter , Peier Karen , Nohynek Brigitte , Fischer Aldo , Stolz Raphael , Cettuzzi Michele , Graf Lukas , Korte Wolfgang
Published: December 2022

Importance

Elderly patients, especially men, are at risk of increased morbidity from coronavirus disease 2019 (COVID-19). Long-term data on troponin I levels in longitudinal observational studies of outpatients with mild to moderate COVID-19 are scarce.

Objective

This controlled cohort study aimed to evaluate the course of troponin I concentrations over a long period in convalescent COVID-19 outpatients with mild to moderate symptoms.

Setting and participants

In this cohort study, individuals with PCR-confirmed, mild to moderate SARS-CoV-2 infection as well as control individuals with confirmed negative PCR and negative SARS-CoV-2 serology were included. Study visits were performed from April 2020 through July 2021 (initialized during the first wave of the corona pandemic in Switzerland). A study visit in patients comprised blood draws every week in the first month and additionally after 8 weeks. This course was repeated in patients observed long-term.

Results

This study enrolled 278 individuals from the Canton of St. Gallen, Switzerland, aged 12–92 years (59.5% women), who had mild to moderate COVID-19 symptoms (outpatients only) and a diagnosis confirmed by positive RT-PCR. Fifty-four of the participants with confirmed SARS-CoV-2 infection were followed for 14 months with repeat cycles of the testing protocol. In addition, 115 symptomatic patients that were PCR and serology negative were enrolled in the same time period as a control group. In COVID-19 patients, low-level troponin I concentrations (cTnI) were significantly increased from baseline until week 9 after positive RT-PCR diagnosis in men older than 54 years [ΔcTnI = 5.0 ng/L (median); 95% CI 4.1–6.0; p = 0.02]. The troponin I concentration remained elevated throughout 14 months in men older than 54 years within the cohort with a prolonged observation period. This statistically significant change in troponin I concentration was not dependent on co-morbidities in this group. ALT, Creatinine, BNP, and D-Dimer values after convalescence did not differ in comparison to the control cohort.

Conclusion

In this analysis of individuals with confirmed SARS-CoV-2 infection, hs troponin I levels of men aged 54 or older significantly increased after infection. They remained elevated for at least 14 months after diagnosis. This suggests the possibility of an ongoing, long-term, low-grade myocardial injury. Further studies with focus on elderly patients and a prolonged observational period are necessary to elucidate whether the phenomenon observed is associated with detectable structural changes to the heart muscle or is without further clinical consequences.
Assessing the risk of cardiovascular events in patients receiving immune checkpoint inhibitors
Authors: Torrente María , Blanco Mariola , Franco Fabio , Garitaonaindia Yago , Calvo Virginia , Collazo-Lorduy Ana , Gutiérrez Lourdes , Sánchez Juan Cristóbal , González-del-Alba Aranzazu , Hernández Roberto , Méndez Miriam , Cantos Blanca , Núñez Beatriz , Sousa Pedro A. C. , Provencio Mariano
Published: December 2022

Background

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, despite their excellent therapeutic effect, these medications typically result in a broad spectrum of toxicity reactions. Immune-related cardiotoxicity is uncommon but can be potentially fatal, and its true incidence is underestimated in clinical trials. The aim of this study is to assess the incidence and identify risk factors for developing a cardiac event in patients treated with ICIs.

Methods

We conducted a single-institution retrospective study, including patients treated with ICIs in our center. The main outcomes were cardiac events (CE) and cardiovascular death.

Results

A total of 378 patients were analyzed. The incidence of CE was 16.7%, during a median follow-up of 50.5 months. The multivariable analysis showed that age, a history of arrhythmia or ischemic heart disease, and prior immune-related adverse events were significantly associated with CE.

Conclusion

CE during ICI treatment are more common than currently appreciated. A complete initial cardiovascular evaluation is recommended, especially in high-risk patients, being necessary a multidisciplinary approach of a specialized cardio-oncology team.
Median nerve stimulation elevates ventricular fibrillation threshold via the cholinergic anti-inflammatory pathway in myocardial infarction canine model
Authors: Wang Xuewen , Qian Yongsheng , Yao Yajun , Wang Youcheng , Zhang Youjing , Zhang Shujuan , Zhao Qingyan
Published: December 2022

Background

Median nerve stimulation (MNS) diminishes regional myocardial ischemia and ventricular arrhythmia; however, the underlying mechanism has not been elucidated.

Methods

In this study, we randomly categorized 22 adult mongrel dogs into a control group, MNS group 1, and MNS group 2. After a 4-week experimental myocardial infarction (MI), ventricular electrophysiology was measured in the MNS group 1 before and after 30 min of MNS. The same measurements were performed in the MNS group 2 dogs via bilateral vagotomy. Venous blood and ventricular tissue were collected to detect molecular indicators related to inflammation and cholinergic pathways by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and Western blot (WB).

Results

No significant changes were reported in the ventricular effective refractory period (ERP) in the MNS group 1 and MNS group 2 dogs before and after MNS. The ventricular fibrillation threshold (VFT) in the MNS group 1 was significantly higher than that in the MNS group 2 (20.3 ± 3.7 V vs. 8.7 ± 2.9 V, P < 0.01). The levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nuclear transcription factor-κB (NF-κB) were lower (P < 0.01), whereas the levels of Ach were higher in the peri-infarct zone tissues in the MNS group 1 dogs than those in the MNS group 2 dogs (P < 0.01).

Conclusion

This study demonstrated that MNS increases VFT in a canine model with MI. The effects of MNS on VFT are potentially associated with the cholinergic anti-inflammatory pathway.
New methods for the diagnosis and monitoring of cognitive function in patients with type 2 diabetes
Authors: Ciudin Andreea , Simó Rafael
Published: December 2022

The presence of type 2 diabetes acts as an accelerator of cognitive impairment (mild cognitive impairment and later dementia), with a significant impact on the management of the disease and its complications. Therefore, it is recommended to perform an annual evaluation of cognitive function in patients with diabetes older than 65 years. Current guidelines still recommend the use of the Minimental State Evaluation Test (MMSE) as screening test, but it has a modest sensitivity and specificity for identifying mild cognitive impairment. This represents an important gap because patients with mild cognitive impairment are at risk of progressing to dementia. The neurocognitive diagnosis is based on complex neuropsychological tests, which require specifically trained personnel and are time consuming, making its routine incorporation into daily clinical practice unfeasible. Therefore, at present there are no reliable biomarkers to identify patients with type 2 diabetes at increased risk of developing cognitive impairment. Since the brain and the retina have a common embryological origin, our Research Group, has worked over the last 10 years evaluating the usefulness of the retina as a “window” to the brain. We provided evidence that retinal microperimetry is a simple, feasible and useful tool for screening and monitoring cognitive function in patients with type 2 diabetes. We propose a review of actual tests recommended for screening of cognitive impairment as well as an update of new emerging methods, such as retinal microperimetry.
Familial dietary intervention in children with excess body weight and its impact on eating habits, anthropometric and biochemical parameters
Authors: Strączek Kamilla , Horodnicka-Józwa Anita , Szmit-Domagalska Justyna , Jackowski Tomasz , Safranow Krzysztof , Petriczko Elżbieta , Walczak Mieczysław
Published: December 2022

Introduction

Obesity is considered a civilisation disease which increases mortality and impairs quality of life, also among children and adolescents. The prevalence of overweight and obesity is steadily increasing in the developmental age population. Environmental factors are responsible for the main reason of excessive adipose tissue accumulation. Among these, poor eating habits and lack of exercise play the largest role. Familial prevalence of obesity and family dietary patterns also receive significant attention. Many specialists believe that the treatment of obesity should be multidirectional, effective and minimally invasive. Therefore, effective and safe methods are being investigated to effectively reduce body weight and improve eating habits. Dietary education programmes are an alternative to improve the health status of obese and overweight children and adolescents. To be fully effective, these programmes should involve the whole family.

Aim of the study

In the face of constantly increasing prevalence of overweight and obesity in the developmental age population and the lack of effective methods to combat its occurrence, it seems appropriate to try to assess the effectiveness of a one-year-long dietary education of children and adolescents with excess body weight on their eating habits and the eating habits of their mothers, as well as selected anthropometric and biochemical parameters in these children using a simple educational tool, the Healthy Food Pyramid.

Patients and methods

The study group consisted of 68 children with overweight and obesity, patients of the Department of Paediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology of the Developmental Age of the Pomeranian Medical University in Szczecin. The study used a proprietary questionnaire to assess dietary habits. Patients participated in six individual educational meetings over a twelve-month period. Eating habits were assessed in children and mothers before and after dietary intervention. Sixty-seven questionnaires before and after the dietary intervention were used for analysis.

Results

Sixty-eight children completed the study. Those who did not complete the study came from families living in rural areas and their mothers mostly had primary or vocational education. One-year dietary education resulted in significant improvements in body weight, waist and hip circumference, WHtR and selected measured carbohydrate and lipid metabolism parameters with the exception of total cholesterol. The one-year dietary intervention did not have the same effect on the change in dietary habits in children and in their mothers.
Optimum non-invasive predictive indicators for metabolic dysfunction-associated fatty liver disease and its subgroups in the Chinese population: A retrospective case-control study
Authors: Liu Jing , Duan Shaojie , Wang Che , Wang Yutong , Peng Hongye , Niu Zuohu , Yao Shukun
Published: December 2022

Objective

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects 25% of the population without approved drug therapy. According to the latest consensus, MAFLD is divided into three subgroups based on different diagnostic modalities, including Obesity, Lean, and Type 2 diabetes mellitus (T2DM) MAFLD subgroups. This study aimed to find out the optimum non-invasive metabolism-related indicators to respectively predict MAFLD and its subgroups.

Design

1058 Chinese participants were enrolled in this study. Anthropometric measurements, laboratory data, and ultrasonography features were collected. 22 metabolism-related indexes were calculated, including fatty liver index (FLI), lipid accumulation product (LAP), waist circumference-triglyceride index (WTI), etc. Logistic regression analyzed the correlation between indexes and MAFLD. Receiver operating characteristics were conducted to compare predictive values among 22 indicators for screening the best indicators to predict MAFLD in different subgroups.

Results

FLI was the best predictor with the maximum odds ratio (OR) values of overall MAFLD (OR: 6.712, 95%CI: 4.766-9.452, area under the curve (AUC): 0.879, P < 0.05) and T2DM MAFLD subgroup (OR: 14.725, 95%CI: 3.712-58.420, AUC: 0.958, P < 0.05). LAP was the best predictor with the maximum OR value of Obesity MAFLD subgroup (OR: 2.689, 95%CI: 2.182-3.313, AUC: 0.796, P < 0.05). WTI was the best predictor with the maximum OR values of Lean MAFLD subgroup (OR: 3.512, 95%CI: 2.286-5.395, AUC: 0.920, P < 0.05).

Conclusion

The best predictors of overall MAFLD, Obesity, Lean, and T2DM MAFLD subgroups were respectively FLI, LAP, WTI, and FLI.
Association of maternal TSH and neonatal metabolism: A large prospective cohort study in China
Authors: Hou Qingzhi , Zou Hui , Zhang Shuping , Lin Jiujing , Nie Wenying , Cui Yazhou , Liu Sijin , Han Jinxiang
Published: December 2022

Aims

Neonatal metabolites are very important in neonatal disease screening, and maternal thyroid hormones play an important role in fetal and neonatal health. Our study aimed to explore the association of maternal thyroid hormones with neonatal metabolites and identify an important time windows.

Methods

Pregnant women were recruited in Jinan Maternity and Child Care Hospital and followed up until delivery. Multivariate generalized linear regression models (GLMs) and restricted cubic spline (RCS) regression analysis models were used to investigate the associations of maternal TSH and FT4 with neonatal metabolites.

Results

In total, 6,653 pairs of mothers and newborns were enrolled in our study. We identified 5 neonatal metabolites, including arginine/ornithine (Arg/Orn), C14:1/C2, C18:1, C3DC+C4OH and C8:1, that were significantly associated with maternal serum TSH during the whole pregnancy (P < 0.05), especially in the first trimester. Moreover, 10 neonatal metabolites were significantly associated with maternal serum FT4 (P < 0.05), most of which had positive correlations with maternal FT4 in the first trimester (P < 0.05). Some neonatal metabolites also had linear or nonlinear dose-effect relationships with maternal serum TSH and FT4 during the whole pregnancy, particularly in the first trimester.

Conclusions

Our study, for the first time, provides epidemiological evidence that maternal serum TSH and FT4, especially during the first trimester, are associated with linear or nonlinear variations in neonatal metabolites. Efforts to identify newborn metabolism levels should carefully consider the effects of maternal thyroid function.
Probiotic treatment with specific lactobacilli does not improve an unfavorable vaginal microbiota prior to fertility treatment—A randomized, double-blinded, placebo-controlled trial
Authors: Jepsen Ida E. , Saxtorph Malene Hviid , Englund Anne Lis Mikkelsen , Petersen Kathrine Birch , Wissing Marie Louise Muff , Hviid Thomas Vauvert F. , Macklon Nicholas
Published: December 2022

Objective

To investigate whether treatment with proprietary lactobacilli-loaded vaginal capsules improves an unfavorable vaginal microbiome diagnosed using a commercially available test and algorithm.

Design

A randomized, double-blinded, placebo-controlled study was conducted in 74 women prior to undergoing fertility treatment at a single university fertility clinic between April 2019 and February 2021. The women were randomly assigned in a 1:1 ratio to receive one vaginal capsule per day for 10 days containing either a culture of more than 108 CFU of Lactobacillus gasseri and more than 108 CFU Lactobacillus rhamnosus (lactobacilli group) or no active ingredient (placebo group). Vaginal swabs for microbiota analysis were taken at enrollment, after treatment and in the cycle following treatment.

Participants and methods

Women aged 18–40 years who prior to fertility treatment were diagnosed with an unfavorable vaginal microbiota, characterized by either a low relative load of Lactobacillus or a high proportion of disrupting bacteria using the criteria of the IS-pro™ diagnostic system (ARTPred, Amsterdam, the Netherlands), were enrolled in the study. The primary outcome measure was the proportion of women with improvement of the vaginal microbiota after intervention.

Results

The vaginal microbiota improved after intervention in 34.2% of all participants (lactobacilli group 28.9%, placebo group 40.0%), with no significant difference in the improvement rate between the lactobacilli and placebo groups, RR = 0.72 (95% CI 0.38–1.38).

Conclusion

This study indicates that administering vaginal probiotics may not be an effective means of modulating the vaginal microbiome for clinical purposes in an infertile population. However, a spontaneous improvement rate of 34.2% over a period of one to three months, confirming the dynamic nature of the vaginal microbiota, indicates that a strategy of postponing further IVF treatment to await microbiota improvement may be relevant in some patients, but further research is needed.

Clinical trial registration

ClinicalTrials.gov, identifier NCT03843112.
An innovative synthetic support for immunocytochemical assessment of cytologically indeterminate (Bethesda III) thyroid nodules
Authors: Taccogna Silvia , Papini Enrico , Novizio Roberto , D’Angelo Martina , Turrini Luca , Persichetti Agnese , Pontecorvi Alfredo , Guglielmi Rinaldo
Published: December 2022

Background

Fine needle aspiration (FNA) is the procedure of choice in the evaluation of thyroid nodules. Nodules with indeterminate cytological categories, Bethesda III and IV, pose challenges in clinical practice and are frequently submitted to diagnostic surgery. CytoFoam Core (CFCS) uses an absorbent foam device inserted into the needle hub to collect the cytological sample aspirated during FNA. Specimen is formalin-fixed and paraffin-embedded.

Aim of the study

Assessing diagnostic efficacy of CFCS, compared to traditional cytology, in re-evaluating thyroid nodules classified as Bethesda III, using post-surgical histology as reference standard.

Method

Retrospective study on 89 patients with a first indeterminate cytological report who were referred to the Department of Endocrinology of Regina Apostolorum Hospital (Albano L. Rome, Italy) for a second FNA. FNA was performed after at least one month under ultrasound guidance with a 23G needle according to the established procedure. During the second procedure, both traditional cytological (TC) smears and a single-pass CFCS specimen were obtained for each patient. On CFCS samples immunocytochemical staining for Galectin-3, HBME-1, and CK-19 was also performed. 51 patients eventually underwent surgery, and their histological diagnoses were compared to the TC and CFCS reports. Four parameters were evaluated: inadequacy rate, rate of persistent indeterminate (Bethesda III and IV) reports, rate of malignancy in persistently indeterminate nodules, and rate of cancer in lesions cytologically classified as malignant.

Results

Non-diagnostic samples were 6 (11.8%) in TC vs 3 (5.9%) in CFCS (p=0.4). Persistent indeterminate samples were 31 (60.8%) in TC vs 19 (37.2%) in CFCS (p=0.01). Rate of malignancy in persistently indeterminate nodules was 8/19 (42.1%) in CFCS vs 9/31 (29%) in TC group (p=0.3). Nine/51 (17.6%) samples were classified as benign by TC vs 21/51 (41.2%) samples by CFCS (p<0.01). All nodules resulted benign at post-surgical evaluation. Five/51 (9.8%) samples were classified as suspicious for malignancy/malignant in TC group against 8/51 (15.7%) samples in CFCS (p=0.5). Post-surgical evaluation confirmed malignancy in all these cases.

Conclusion

CFCS demonstrated greater diagnostic accuracy than TC in repeat FNA assessment of cytologically indeterminate nodules. CFCS increased the conclusive diagnosis rate and decreased the number of cytologically indeterminate cases.