bluuebunny/crossref_metadata_2025 huggingface dataset:
The Differential Impact of Screen Time on Children’s Wellbeing
Authors: Belton Sarahjane , Issartel Johann , Behan Stephen , Goss Hannah , Peers Cameron
Published: August 2021

Increased screen time has been found to be associated with a number of negative health and wellbeing indicators in youth populations. An increasing number of studies have investigated the association between screen time and wellbeing in adolescents, but evidence in younger children is still emerging. This 2017 study explored the effect of leisure screen time and gender on dimensions of wellbeing (measured using KIDSCREEN-27) in a national sample of 897 Irish primary school children aged 8–12 years. Participants had a mean age of 10.9 ± 1.16 years and were 47.7% female. Just over 30% of the sample accumulated 2 h or more of leisure screen time daily. Results show that there was no significant interaction between screen time category (<2 h/2 h + daily) and gender on overall wellbeing, while controlling for BMI. Children who self-reported <2 h of leisure screen time scored significantly higher on four dimensions of wellbeing: physical, parental, peers, and school, but not psychological. This study supports the growing evidence of the impact that leisure screen time has on health. Further longitudinal research investigating the impact of sub-categories of leisure screen time behaviour on wellbeing is warranted.
Quality of Life and Physical Activity of Persons with Spinal Cord Injury
Authors: Filipcic Tjasa , Sember Vedrana , Pajek Maja , Jerman Janez
Published: August 2021

The higher quality of life of people with spinal cord injury is closely related with their reintegration into the social environment. Social reintegration is a demanding and complex process, requiring individuals to become active again and acquire age-, gender-, and culture-appropriate roles and social status. It also involves independence and productive behavior as part of multiple interpersonal relationships with family, friends, and others. In order to establish whether individuals with spinal cord injury who are physically active subjectively rate their quality of life to be higher compared to those who are not, sixty-two respondents from Slovenia with spinal cord injury were interviewed. Thirty-one of them were physically active, and 31 were not. The level of injury of the responders was from Th6–Th12. The participants gave the highest assessments to their interpersonal relationships, and the lowest to their satisfaction with material prosperity. Data comparison showed that subjective estimates in all areas of quality of life are higher in respondents who were involved in physical activity after their injury. The results may encourage persons with spinal cord injury to participate more often in sports programs, and also encourage others to do so.
Rapid Test Ag 2019-nCoV (PROGNOSIS, BIOTECH, Larissa, Greece); Performance Evaluation in Hospital Setting with Real Time RT-PCR
Authors: Kyritsi Maria , Vontas Alexandros , Voulgaridi Ioanna , Matziri Alexia , Komnos Apostolos , Babalis Dimitris , Papadogoulas Antonios , Oikonomou Aikaterini , Mouchtouri Varvara A. , Speletas Matthaios , Hadjichristodoulou Christos
Published: August 2021

Introduction: Rapid antigen tests (RATs) are convenient for SARS-CoV-2 detection because they are simpler and faster than nucleic acid amplification tests (NAATs). This study aimed to assess the accuracy of a locally manufactured test; Rapid Test Ag 2019-nCoV (PROGNOSIS, BIOTECH, Larissa, Greece) in a clinical setting and during mass screening. Methods: Nasopharyngeal samples from 624 individuals were analyzed. The results of the rapid test were compared to real-time reverse-transcription quantitative polymerase chain reaction (RT-qPCR). At the end of the test’s procedure, positive test strips were scanned in an S-Flow reader in order to roughly estimate the antigen concentration. Results: The lower limit of detection of the test was 468.75 genome copies/mL. The PROGNOSIS rapid test displayed a sensitivity of 85.5% (141/165) (95%CI: 79.1–90.5) and a specificity of 99.8% (458/459) (95%CI: 98.8–100.0%). The general inter-rater agreement was 0.89 (95%CI: 85.1–93.3). The regression analysis between the S-flow reader measurements (viral antigen) and the viral load of the positive samples demonstrated a weak correlation (R2 = 0.288, p < 0.001). Conclusion: The Rapid Test Ag 2019-nCoV demonstrated sufficient sensitivity, excellent specificity and could be available to be used with low overall cost. Thus, it could be used as point of care test, but also for mass screening for rapid detection of infected persons (e.g., for travelers).
Zebrafish Bioassay for Screening Therapeutic Candidates Based on Melanotrophic Activity
Authors: Hong Ted I. , Hwang Kyu-Seok , Choi Tae-Ik , Kleinau Gunnar , Scheerer Patrick , Bang Jeong Kyu , Jung Seung-Hyun , Kim Cheol-Hee
Published: August 2021

In this study, we used the zebrafish animal model to establish a bioassay by which physiological efficacy differential of alpha-melanocyte-stimulating hormone (α-MSH) analogues could be measured by melanosome dispersion in zebrafish larvae. Brain-skin connection research has purported the interconnectedness between the nervous system and skin physiology. Accordingly, the neuropeptide α-MSH is a key regulator in several physiological processes, such as skin pigmentation in fish. In mammals, α-MSH has been found to regulate motivated behavior, appetite, and emotion, including stimulation of satiety and anxiety. Several clinical and animal model studies of autism spectrum disorder (ASD) have already demonstrated the effectiveness of α-MSH in restoring the social deficits of autism. Therefore, we sought to analyze the effect of synthetic and naturally-occurring α-MSH variants amongst different species. Our results showed that unique α-MSH derivatives from several fish species produced differential effects on the degree of melanophore dispersion. Using α-MSH human form as a standard, we could identify derivatives that induced greater physiological effects; particularly, the synthetic analogue melanotan-II (MT-II) exhibited a higher capacity for melanophore dispersion than human α-MSH. This was consistent with previous findings in an ASD mouse model demonstrating the effectiveness of MT-II in improving ASD behavioral symptoms. Thus, the melanophore assay may serve as a useful screening tool for therapeutic candidates for novel drug discovery.
Mood Stabilizers in Psychiatric Disorders and Mechanisms Learnt from In Vitro Model Systems
Authors: Nayak Ritu , Rosh Idan , Kustanovich Irina , Stern Shani
Published: August 2021

Bipolar disorder (BD) and schizophrenia are psychiatric disorders that manifest unusual mental, behavioral, and emotional patterns leading to suffering and disability. These disorders span heterogeneous conditions with variable heredity and elusive pathophysiology. Mood stabilizers such as lithium and valproic acid (VPA) have been shown to be effective in BD and, to some extent in schizophrenia. This review highlights the efficacy of lithium and VPA treatment in several randomized, controlled human trials conducted in patients suffering from BD and schizophrenia. Furthermore, we also address the importance of using induced pluripotent stem cells (iPSCs) as a disease model for mirroring the disease’s phenotypes. In BD, iPSC-derived neurons enabled finding an endophenotype of hyperexcitability with increased hyperpolarizations. Some of the disease phenotypes were significantly alleviated by lithium treatment. VPA studies have also reported rescuing the Wnt/β-catenin pathway and reducing activity. Another significant contribution of iPSC models can be attributed to studying the molecular etiologies of schizophrenia such as abnormal differentiation of patient-derived neural stem cells, decreased neuronal connectivity and neurite number, impaired synaptic function, and altered gene expression patterns. Overall, despite significant advances using these novel models, much more work remains to fully understand the mechanisms by which these disorders affect the patients’ brains.
Synthetic NAC 71-82 Peptides Designed to Produce Fibrils with Different Protofilament Interface Contacts
Authors: Näsström Thomas , Dahlberg Tobias , Malyshev Dmitry , Ådén Jörgen , Andersson Per Ola , Andersson Magnus , Karlsson Björn C. G.
Published: August 2021

Alpha-synucleinopathies are featured by fibrillar inclusions in brain cells. Although α-synuclein fibrils display structural diversity, the origin of this diversity is not fully understood. We used molecular dynamics simulations to design synthetic peptides, based on the NAC 71-82 amino acid fragment of α-synuclein, that govern protofilament contacts and generation of twisted fibrillar polymorphs. Four peptides with structures based on either single or double fragments and capped or non-capped ends were selected for further analysis. We determined the fibrillar yield and the structures from these peptides found in the solution after fibrillisation using protein concentration determination assay and circular dichroism spectroscopy. In addition, we characterised secondary structures formed by individual fibrillar complexes using laser-tweezers Raman spectroscopy. Results suggest less mature fibrils, based on the lower relative β-sheet content for double- than single-fragment peptide fibrils. We confirmed this structural difference by TEM analysis which revealed, in addition to short protofibrils, more elongated, twisted and rod-like fibril structures in non-capped and capped double-fragment peptide systems, respectively. Finally, time-correlated single-photon counting demonstrated a difference in the Thioflavin T fluorescence lifetime profiles upon fibril binding. It could be proposed that this difference originated from morphological differences in the fibril samples. Altogether, these results highlight the potential of using peptide models for the generation of fibrils that share morphological features relevant for disease, e.g., twisted and rod-like polymorphs.
Is Cenobamate the Breakthrough We Have Been Wishing for?
Authors: Specchio Nicola , Pietrafusa Nicola , Vigevano Federico
Published: August 2021

Close to one-third of patients with epilepsies are refractory to current anti-seizure medications; however, trials with cenobamate suggest effectiveness in such patients with focal onset seizures. We searched for data published or otherwise reported on cenobamate and outlined these here. Despite being marketed in the USA, few studies are yet published in full, and trials are ongoing. Nevertheless, cenobamate showed potential for a high degree of efficacy in reducing seizures with an unprecedented seizure-free rate of up to 28%. Rare cases of hypersensitivity reactions seen in early trials seem to be avoided by the current recommended titration schedule. Other adverse events were rated mild-to-moderate and most commonly included dizziness, drowsiness, and headache. If data are confirmed in further published trials, cenobamate will be a welcome new treatment and further analyses may identify those that will benefit the most.
RGS5 Determines Neutrophil Migration in the Acute Inflammatory Phase of Bleomycin-Induced Lung Injury
Authors: Sharma Neha , Nagaraj Chandran , Nagy Bence M. , Marsh Leigh M. , Bordag Natalie , Zabini Diana , Wygrecka Malgorzata , Klepetko Walter , Gschwandtner Elisabeth , Genové Guillem , Heinemann Akos , Weir E Kenneth , Kwapiszewska Grazyna , Olschewski Horst , Olschewski Andrea
Published: August 2021

The regulator of G protein signaling (RGS) represents a widespread system of controllers of cellular responses. The activities of the R4 subfamily of RGSs have been elucidated in allergic pulmonary diseases. However, the R4 signaling in other inflammatory lung diseases, with a strong cellular immune response, remained unexplored. Thus, our study aimed to discern the functional relevance of the R4 family member, RGS5, as a potential modulating element in this context. Gene profiling of the R4 subfamily showed increased RGS5 expression in human fibrosing lung disease samples. In line with this, RGS5 was markedly increased in murine lungs following bleomycin injury. RGS knock-out mice (RGS-/-) had preserved lung function while control mice showed significant combined ventilatory disorders three days after bleomycin application as compared to untreated control mice. Loss of RGS5 was associated with a significantly reduced neutrophil influx and tissue myeloperoxidase expression. In the LPS lung injury model, RGS5-/- mice also failed to recruit neutrophils into the lung, which was accompanied by reduced tissue myeloperoxidase levels after 24 h. Our in-vitro assays showed impaired migration of RGS5-/- neutrophils towards chemokines despite preserved Ca2+ signaling. ERK dephosphorylation might play a role in reduced neutrophil migration in our model. As a conclusion, loss of RGS5 preserves lung function and attenuates hyperinflammation in the acute phase of bleomycin-induced pulmonary fibrosis and LPS-induced lung injury. Targeting RGS5 might alleviate the severity of exacerbations in interstitial lung diseases.
High Resolution Analysis of Proteome Dynamics during Bacillus subtilis Sporulation
Authors: Tu Zhiwei , Dekker Henk L. , Roseboom Winfried , Swarge Bhagyashree N. , Setlow Peter , Brul Stanley , Kramer Gertjan
Published: August 2021

Bacillus subtilis vegetative cells switch to sporulation upon nutrient limitation. To investigate the proteome dynamics during sporulation, high-resolution time-lapse proteomics was performed in a cell population that was induced to sporulate synchronously. Here, we are the first to comprehensively investigate the changeover of sporulation regulatory proteins, coat proteins, and other proteins involved in sporulation and spore biogenesis. Protein co-expression analysis revealed four co-expressed modules (termed blue, brown, green, and yellow). Modules brown and green are upregulated during sporulation and contain proteins associated with sporulation. Module blue is negatively correlated with modules brown and green, containing ribosomal and metabolic proteins. Finally, module yellow shows co-expression with the three other modules. Notably, several proteins not belonging to any of the known transcription regulons were identified as co-expressed with modules brown and green, and might also play roles during sporulation. Finally, levels of some coat proteins, for example morphogenetic coat proteins, decreased late in sporulation.
Heterologous Complementation of SPO11-1 and -2 Depends on the Splicing Pattern
Authors: Sprink Thorben , Hartung Frank
Published: August 2021

In the past, major findings in meiosis have been achieved, but questions towards the global understanding of meiosis remain concealed. In plants, one of these questions covers the need for two diverse meiotic active SPO11 proteins. In Arabidopsis and other plants, both meiotic SPO11 are indispensable in a functional form for double strand break induction during meiotic prophase I. This stands in contrast to mammals and fungi, where a single SPO11 is present and sufficient. We aimed to investigate the specific function and evolution of both meiotic SPO11 paralogs in land plants. By performing immunostaining of both SPO11-1 and -2, an investigation of the spatiotemporal localization of each SPO11 during meiosis was achieved. We further exchanged SPO11-1 and -2 in Arabidopsis and could show a species-specific function of the respective SPO11. By additional changes of regions between SPO11-1 and -2, a sequence-specific function for both the SPO11 proteins was revealed. Furthermore, the previous findings about the aberrant splicing of each SPO11 were refined by narrowing them down to a specific developmental phase. These findings let us suggest that the function of both SPO11 paralogs is highly sequence specific and that the orthologs are species specific.
A-FABP in Metabolic Diseases and the Therapeutic Implications: An Update
Authors: Li Hang-Long , Wu Xiaoping , Xu Aimin , Hoo Ruby Lai-Chong
Published: August 2021

Adipocyte fatty acid-binding protein (A-FABP), which is also known as ap2 or FABP4, is a fatty acid chaperone that has been further defined as a fat-derived hormone. It regulates lipid homeostasis and is a key mediator of inflammation. Circulating levels of A-FABP are closely associated with metabolic syndrome and cardiometabolic diseases with imminent diagnostic and prognostic significance. Numerous animal studies have elucidated the potential underlying mechanisms involving A-FABP in these diseases. Recent studies demonstrated its physiological role in the regulation of adaptive thermogenesis and its pathological roles in ischemic stroke and liver fibrosis. Due to its implication in various diseases, A-FABP has become a promising target for the development of small molecule inhibitors and neutralizing antibodies for disease treatment. This review summarizes the clinical and animal findings of A-FABP in the pathogenesis of cardio-metabolic diseases in recent years. The underlying mechanism and its therapeutic implications are also highlighted.
Effects of Cardiolipin on the Conformational Dynamics of Membrane-Anchored Bcl-xL
Authors: Tyagi Vivek , Vasquez-Montes Victor , Freites J. Alfredo , Kyrychenko Alexander , Tobias Douglas J. , Ladokhin Alexey S.
Published: August 2021

The anti-apoptotic protein Bcl-xL regulates apoptosis by preventing the permeation of the mitochondrial outer membrane by pro-apoptotic pore-forming proteins, which release apoptotic factors into the cytosol that ultimately lead to cell death. Two different membrane-integrated Bcl-xL constructs have been identified: a membrane-anchored and a membrane-inserted conformation. Here, we use molecular dynamics simulations to study the effect of the mitochondrial specific lipid cardiolipin and the protein protonation state on the conformational dynamics of membrane-anchored Bcl-xL. The analysis reveals that the protonation state of the protein and cardiolipin content of the membrane modulate the orientation of the soluble head region (helices α1 through α7) and hence the exposure of its BH3-binding groove, which is required for its interaction with pro-apoptotic proteins.
The Aneugenicity of Ketone Bodies in Colon Epithelial Cells Is Mediated by Microtubule Hyperacetylation and Is Blocked by Resveratrol
Authors: Sudo Haruka , Kubo Akira
Published: August 2021

Diabetes mellitus (DM) is considered to be associated with an increased risk of colorectal cancer. Recent studies have also revealed that tubulin hyperacetylation is caused by a diabetic status and we have reported previously that, under microtubule hyperacetylation, a microtubule severing protein, katanin-like (KL) 1, is upregulated and contributes to tumorigenesis. To further explore this phenomenon, we tested the effects of the ketone bodies, acetoacetate and β-hydroxybutyrate, in colon and fibroblast cells. Both induced microtubule hyperacetylation that responded differently to a histone deacetylase 3 knockdown. These two ketone bodies also generated intracellular reactive oxygen species (ROS) and hyperacetylation was commonly inhibited by ROS inhibitors. In a human fibroblast-based microtubule sensitivity test, only the KL1 human katanin family member showed activation by both ketone bodies. In primary cultured colon epithelial cells, these ketone bodies reduced the tau protein level and induced KL1- and α-tubulin acetyltransferase 1 (ATAT1)-dependent micronucleation. Resveratrol, known for its tumor preventive and tubulin deacetylation effects, inhibited this micronucleation. Our current data thus suggest that the microtubule hyperacetylation induced by ketone bodies may be a causal factor linking DM to colorectal carcinogenesis and may also represent an adverse effect of them that needs to be controlled if they are used as therapeutics.
Immune Checkpoint Therapy: Tumor Draining Lymph Nodes in the Spotlights
Authors: Fransen Marieke F. , van Hall Thorbald , Ossendorp Ferry
Published: August 2021

Tumor-draining lymph nodes play a paradoxical role in cancer. Surgeons often resect these sentinel lymph nodes to determine metastatic spread, thereby enabling prognosis and treatment. However, lymph nodes are vital organs for the orchestration of immune responses, due to the close encounters of dedicated immune cells. In view of the success of immunotherapy, the removal of tumor-draining lymph nodes needs to be re-evaluated and viewed in a different light. Recently, an important role for tumor-draining lymph nodes has been proposed in the immunotherapy of cancer. This new insight can change the use of immune checkpoint therapy, particularly with respect to the use in neoadjuvant settings in which lymph nodes are still operational.
Epigenetic Modulation of Vasopressin Expression in Health and Disease
Authors: Török Bibiána , Fazekas Csilla Lea , Szabó Adrienn , Zelena Dóra
Published: August 2021

Vasopressin is a ubiquitous molecule playing an important role in a wide range of physiological processes thereby implicated in the pathomechanism of many disorders. Its effect is well characterized through V2 receptors, which regulates the water resorption in kidney, while its vasoconstrictory effect through V1a receptor also received a lot of attention in the maintenance of blood pressure during shock. However, the most striking is its central effect both through the V1b receptors in stress-axis regulation as well as through V1a receptors regulating many aspects of our behavior (e.g., social behavior, learning and memory). Vasopressin has been implicated in the development of depression, due to its connection with chronic stress, as well as schizophrenia because of its involvement in social interactions and memory processes. Epigenetic changes may also play a role in the development of these disorders. The possible mechanism includes DNA methylation, histone modification and/or micro RNAs, and these possible regulations will be in the focus of our present review.
Classification and Treatment of Diseases in the Age of Genome Medicine Based on Pathway Pathology
Authors: Petersen Iver
Published: August 2021

The focus of pathology as a biomedical discipline is the identification of the pathomechanisms of diseases and the integration of this knowledge into routine diagnosis and classification. Standard tools are macroscopic and microscopic analysis complemented by immunohistochemistry and molecular pathology. So far, classification has been based on the paradigm of cellular pathology established by Rudolf Virchow and others more than 150 years ago, stating that diseases originate from diseased cells. This dogma is meanwhile challenged by the fact that cells can be fully reprogrammed. Many diseases are nowadays considered to originate from undifferentiated stem cells, induced into a diseased state by genetic or epigenetic alterations. In addition, the completion of the Human Genome Project, with the identification of more than 20.000 genes and a much higher number of gene variants and mutations, led to the concept that diseases are dominated by genetics/epigenetics rather than cells of origin. The axiom of cellular pathology, however, still holds true, as cells are the smallest animate units from which diseases originate. Medical doctors and researchers nowadays have to deal with a tremendous amount of data. The International Classification of Diseases will expand from 14.400 entities/codes in ICD-10 to more than 55.000 in ICD-11. In addition, large datasets generated by “genomics“, e.g., whole-genome sequencing, expression profiling or methylome analysis, are meanwhile not only applied in research but also introduced into clinical settings. It constitutes a major task to incorporate all the data into routine medical work. Pathway pathology may help solve this problem. It is based on the realization that diseases are characterized by three essential components: (i) cells of origin/cellular context and (ii) the alteration of cellular as well as (iii) molecular/signal transduction pathways. The concept is illustrated by elaborating on two key cellular pathways, i.e., the cellular senescence of normal cells and the immortality of cancer cells, and by contrasting single cell/single pathway diseases, such as mycoplasma and coughing pneumonia, with complex diseases such as cancer, with multiple cell types as well as multiple affected cellular and signaling pathways. Importantly, the concept of pathway pathology is not just intended to classify disease, but also to conceive new treatment modalities. This article is dedicated to Dr. Leonard Hayflick, who made basic discoveries in pathway pathology not only by identifying cells causing disease (Mycoplasma pneumoniae) and establishing cell strains for treating disease (WI-38 for viral vaccines), but also by first describing cellular senescence and immortality.
Ophelimus bipolaris sp. n. (Hymenoptera, Eulophidae), a New Invasive Eucalyptus Pest and Its Host Plants in China
Authors: Chen Hua-Yan , Yao Jie-Min , Huang Shao-Bin , Pang Hong
Published: August 2021

Eucalyptus species have become one of the most commonly planted trees worldwide, including China, due to their fast growth and various commercial applications. However, the productivity of Eucalyptus plantations has been threatened by exotic invasive insect pests in recent years. Among these pests, gall inducers of the genus Ophelimus of the Eulophidae family are among the most important invasive species in Eucalyptus plantations. We report here for the first time the presence of a new invasive Eucalyptus gall wasp, Ophelimus bipolaris sp. n., in Guangzhou, China, which also represents the first species of the genus reported from China. The identity of the new species was confirmed by an integrative approach combing biological, morphological and molecular evidence. The new species is described and illustrated. This wasp induces galls only on the leaf blade surface of four Eucalyptus species: E. grandis, E. grandis × E. urophylla, E. tereticornis and E. urophylla. Our preliminary observation showed that O. bipolaris could complete a life cycle on E. urophylla in approximately 2 months under local climatic conditions (23.5–30 °C). Considering the severe damage it may cause to Eucalyptus production, further investigations of its biology and control are urgently needed in China.
The Association between Foot and Ulcer Microcirculation Measured with Laser Speckle Contrast Imaging and Healing of Diabetic Foot Ulcers
Authors: Mennes Onno A. , van Netten Jaap J. , van Baal Jeff G. , Slart Riemer H. J. A. , Steenbergen Wiendelt
Published: August 2021

Diagnosis of peripheral artery disease in people with diabetes and a foot ulcer using current non-invasive blood pressure measurements is challenging. Laser speckle contrast imaging (LSCI) is a promising non-invasive technique to measure cutaneous microcirculation. This study investigated the association between microcirculation (measured with both LSCI and non-invasive blood pressure measurement) and healing of diabetic foot ulcers 12 and 26 weeks after measurement. We included sixty-one patients with a diabetic foot ulcer in this prospective, single-center, observational cohort-study. LSCI scans of the foot, ulcer, and ulcer edge were conducted, during baseline and post-occlusion hyperemia. Non-invasive blood pressure measurement included arm, foot, and toe pressures and associated indices. Healing was defined as complete re-epithelialization and scored at 12 and 26 weeks. We found no significant difference between patients with healed or non-healed foot ulcers for both types of measurements (p = 0.135–0.989). ROC curves demonstrated moderate sensitivity (range of 0.636–0.971) and specificity (range of 0.464–0.889), for LSCI and non-invasive blood pressure measurements. Therefore, no association between diabetic foot ulcer healing and LSCI-measured microcirculation or non-invasive blood pressure measurements was found. The healing tendency of diabetic foot ulcers is difficult to predict based on single measurements using current blood pressure measurements or LSCI.
Mechanical Thrombectomy in Acute Terminal Internal Carotid Artery Occlusions Using a Large Manually Expandable Stentretriever (Tiger XL Device): Multicenter Initial Experience
Authors: Maus Volker , Hüsken Sabeth , Kalousek Vladimir , Karwacki Grzegorz Marek , Nordmeyer Hannes , Kleffner Ilka , Weber Werner , Fischer Sebastian
Published: August 2021

Background: The recently introduced Tigertriever XL Device for treatment of cerebral vessel occlusions combines manual adjustability and maximum length in one device. In this study, we report our initial experience with the Tigertriever XL in terminal ICA occlusions. Methods: Retrospective multicenter analysis of acute terminal ICA occlusions treated by mechanical thrombectomy using the Tigertriever XL Device. Results: 23 patients were treated using the Tigetriever XL due to an acute occlusion of the terminal ICA. The overall successful reperfusion rate after a median of two maneuvers using the Tigertriever XL Device was 78.3% (mTICI 2b-3). In 43.5% (10/23) additional smaller devices were applied to treat remaining occlusions in downstream territories, which resulted in a final successful reperfusion rate of 95.7%. Device related complications did not occur. Two symptomatic intracerebral hemorrhages (sICH) were observed. Conclusions: The Tigertriever XL Device might be a helpful tool in the treatment of ICA terminus occlusions with large clot burden resulting in high reperfusion rates. This is mainly related to the manual adjustability of the device combined with the maximum length.
Use of Phentolamine Mesylate in Implant Surgery: Analysis of Adverse Effects and Haemodynamic Changes
Authors: Vintanel-Moreno Clara , Martínez-González José María , Martínez-Rodríguez Natalia , Meniz-García Cristina , Leco-Berrocal Isabel
Published: August 2021

The clinical application of phentolamine mesylate (PM) as an anaesthetic reversal agent has been documented in the paediatric population and in conservative dentistry, but no studies have been conducted regarding dental implant surgery. A prospective randomised study was conducted on 60 patients eligible for mandibular implant treatment, randomly divided between a control group (CG) and an experimental group (EG), to whom PM was administered. Haemodynamic changes, adverse effects and patient satisfaction were assessed. No statistically significant differences in haemodynamic changes and postoperative pain were found between CG and EG (p < 0.05), except for systolic blood pressure (SBP), which increased slightly in EG, without posing a risk to patients. There were no differences in the occurrence of adverse effects between the two groups, except for greater difficulty in chewing and biting (p < 0.05) in CG and greater pain in the injection area (p = 0.043) in EG. Among EG patients, 83.3% reported that they would request PM again for future dental treatment. The use of PM offers an alternative to implant surgery, thereby increasing patients’ quality of life without increasing the risks.
Hemodynamics Prior to Valve Replacement for Severe Aortic Stenosis and Pulmonary Hypertension during Long-Term Follow-Up
Authors: Weber Lukas , Rickli Hans , Haager Philipp K. , Joerg Lucas , Weilenmann Daniel , Chronis Joannis , Rigger Johannes , Buser Marc , Ehl Niklas F. , Maeder Micha T.
Published: August 2021

(1) Background: Pulmonary hypertension after aortic valve replacement (AVR; post-AVR PH) carries a poor prognosis. We assessed the pre-AVR hemodynamic characteristics of patients with versus without post-AVR PH. (2) Methods: We studied 205 patients (mean age 75 ± 10 years) with severe AS (indexed aortic valve area 0.42 ± 0.12 cm2/m2, left ventricular ejection fraction 58 ± 11%) undergoing right heart catheterization (RHC) prior to surgical (70%) or transcatheter (30%) AVR. Echocardiography to assess post-AVR PH, defined as estimated systolic pulmonary artery pressure > 45 mmHg, was performed after a median follow-up of 15 months. (3) Results: There were 83/205 (40%) patients with pre-AVR PH (defined as mean pulmonary artery pressure (mPAP) ≥ 25 mmHg by RHC), and 24/205 patients (12%) had post-AVR PH (by echocardiography). Among the patients with post-AVR PH, 21/24 (88%) had already had pre-AVR PH. Despite similar indexed aortic valve area, patients with post-AVR PH had higher mPAP, mean pulmonary artery wedge pressure (mPAWP) and pulmonary vascular resistance (PVR), and lower pulmonary artery capacitance (PAC) than patients without. (4) Conclusions: Patients presenting with PH roughly one year post-AVR already had worse hemodynamic profiles in the pre-AVR RHC compared to those without, being characterized by higher mPAP, mPAWP, and PVR, and lower PAC despite similar AS severity.
The Defect in Regulatory T Cells in Psoriasis and Therapeutic Approaches
Authors: Kanda Naoko , Hoashi Toshihiko , Saeki Hidehisa
Published: August 2021

Psoriasis is a chronic inflammatory skin disease characterized by accelerated tumor necrosis factor-α/interleukin (IL)-23/IL-17 axis. Patients with psoriasis manifest functional defects in CD4+CD25+ forkhead box protein 3 (Foxp3)+ regulatory T cells (Tregs), which suppress the excess immune response and mediate homeostasis. Defects in Tregs contribute to the pathogenesis of psoriasis and may attribute to enhanced inhibition and/or impaired stimulation of Tregs. IL-23 induces the conversion of Tregs into type 17 helper T (Th17) cells. IL-17A reduces transforming growth factor (TGF)-β1 production, Foxp3 expression, and suppresses Treg activity. Short-chain fatty acids (SCFAs), butyrate, propionate, and acetate are microbiota-derived fermentation products that promote Treg development and function by inducing Foxp3 expression or inducing dendritic cells or intestinal epithelial cells to produce retinoic acids or TGF-β1, respectively. The gut microbiome of patients with psoriasis revealed reduced SCFA-producing bacteria, Bacteroidetes, and Faecallibacterium, which may contribute to the defect in Tregs. Therapeutic agents currently used, viz., anti-IL-23p19 or anti-IL-17A antibodies, retinoids, vitamin D3, dimethyl fumarate, narrow-band ultraviolet B, or those under development for psoriasis, viz., signal transducer and activator of transcription 3 inhibitors, butyrate, histone deacetylase inhibitors, and probiotics/prebiotics restore the defected Tregs. Thus, restoration of Tregs is a promising therapeutic target for psoriasis.
A Machine Learning Predictive Model for Post-Ureteroscopy Urosepsis Needing Intensive Care Unit Admission: A Case–Control YAU Endourology Study from Nine European Centres
Authors: Pietropaolo Amelia , Geraghty Robert M. , Veeratterapillay Rajan , Rogers Alistair , Kallidonis Panagiotis , Villa Luca , Boeri Luca , Montanari Emanuele , Atis Gokhan , Emiliani Esteban , Sener Tarik Emre , Al Jaafari Feras , Fitzpatrick John , Shaw Matthew , Harding Chris , Somani Bhaskar K.
Published: August 2021

Introduction: With the rise in the use of ureteroscopy and laser stone lithotripsy (URSL), a proportionate increase in the risk of post-procedural urosepsis has also been observed. The aims of our paper were to analyse the predictors for severe urosepsis using a machine learning model (ML) in patients that needed intensive care unit (ICU) admission and to make comparisons with a matched cohort. Methods: A retrospective study was conducted across nine high-volume endourology European centres for all patients who underwent URSL and subsequently needed ICU admission for urosepsis (Group A). This was matched by patients with URSL without urosepsis (Group B). Statistical analysis was performed with ‘R statistical software’ using the ‘randomforests’ package. The data were segregated at random into a 70% training set and a 30% test set using the ‘sample’ command. A random forests ML model was then built with n = 300 trees, with the test set used for internal validation. Diagnostic accuracy statistics were generated using the ‘caret’ package. Results: A total of 114 patients were included (57 in each group) with a mean age of 60 ± 16 years and a male:female ratio of 1:1.19. The ML model correctly predicted risk of sepsis in 14/17 (82%) cases (Group A) and predicted those without urosepsis for 12/15 (80%) controls (Group B), whilst overall it also discriminated between the two groups predicting both those with and without sepsis. Our model accuracy was 81.3% (95%, CI: 63.7–92.8%), sensitivity = 0.80, specificity = 0.82 and area under the curve = 0.89. Predictive values most commonly accounting for nodal points in the trees were a large proximal stone location, long stent time, large stone size and long operative time. Conclusion: Urosepsis after endourological procedures remains one of the main reasons for ICU admission. Risk factors for urosepsis are reasonably accurately predicted by our innovative ML model. Focusing on these risk factors can allow one to create predictive strategies to minimise post-operative morbidity.
Soil fertility and corn yield changes depending on the tillage system
Authors:   National Center of Grain named after P. P. Lukyanenko, Mnatsakanyan A.A.
Published: August 2021

Tillage system is one of the factors that influences crop yield. The aim of the research was to determine the influence of the basic tillage systems on the change in soil fertility, yield and quality of corn grain in the soil and climatic conditions of the central zone of the Krasnodar Territory. The surveys were conducted in 2018–2020 on the experimental fields of the FSBSO “National Center of Grain named after P. P. Lukyanenko”. Soil – chernozems leached. All the experiments were carried out according to the standard methodology. In a stationary experiment, observations were performed to study several tillage practices: conventional tillage (25 cm depth plowing), mulch tillage with soil decompaction (reduced tillage done with a chisel plow to a depth of 32 cm for row crops), mulch tillage (deep tillage is excluded, disking to a depth of 10 cm twice or thrice is used instead). Plowing to a 25 cm depth improves the bulk of the soil in the 0–30 cm layer. However, chiseling to a depth of 32 cm and disking to a depth of 10 cm twice or thrice caused soil compaction. Standard tillage practice led to a decrease in the number of agronomically valuable aggregates (61.1 %) and their water resistance (59.4 %) compared to soil decompaction and minimum-tillage systems. The highest rates of productive moisture reserves were on the plots with traditional tillage and decompaction (140.6 and 141.5 mm, respectively, which is 14.7 % higher compared to the minimum mulching). The studied soil cultivation systems did not affect “1000-grain weight” but significantly affected the yield of grain from one ear (124.3 g) and the number of formed ears per one plant (1.04 pcs.). The corn yield on the fields with traditional and decompaction tillage methods was 56.9 and 55.9 c/ha, respectively; on minimum-tillage system, it decreased by 4.8 %. Protein content in grain harvested from the plots with traditional tillage practice was 11.4 %, which is higher compared to the minimum-tillage system. No significant differences were detected for crude ash and dry matter.
Chromatographic profiles of antifungal exo- and endometabolites of Bacillus velezensis
Authors:   Federal Research Center of Biological Plant Protection, Sidorova T.M. , Asaturova A.M. ,   Federal Research Center of Biological Plant Protection, Allakhverdyan V.V. ,   Federal Research Center of Biological Plant Protection
Published: August 2021

The antifungal activity of the Bacillus bacteria is based on their ability to produce metabolites. Therefore, when selecting a strain that produces an effective biofungicide, it is necessary to assess the metabolism of bacteria. The aim of this work is to isolate exo- and endometabolites of the promising B. velezensis BZR 336g and B. velezensis BZR 517 strains and assess their antifungal activity. Studies were carried out in 2020–2021. The object of the study is a liquid culture of the B. velezensis BZR 336g and B. velezensis BZR 517 strains. Methods of liquid extraction, ascending thin layer chromatography (TLC), bioautography with a test-culture of Fusarium oxysporum var. orthoceras and Alternaria sp. fungi were used to analyze metabolites. The ability of the strains to accumulate a complex of active metabolites showing antifungal effect from fungistatic to fungicidal action was revealed. On the bioautogram of exometabolites, we found two most pronounced zones (Rf 0.18 and 0.29) of Fusarium oxysporum var. orthoceras BZR P1 growth inhibition (fungicide). Zones with Rf 0.58 for B. velezensis BZR 336g and Rf 0.70 for B. velezensis BZR 517 correspond to the test fungus growth retardation (fungistatic). Significant suppression of Alternaria sp. BZR P8 growth was also observed in two zones (Rf 0.18 and 0.29). The use of surfactin, iturin A, fengycin (Sigma-Aldrich®) in the TLC analysis made it possible to detect similar lipopeptides in the composition of metabolite complexes produced by the studied bacteria. It should be noted that the studied strains differed both in their ability to produce metabolites of different structure (can be found when analyzing chromatograms under ultraviolet light) and in their effect on phytopathogenic fungi in vitro. This may indicate possible differences in the mechanism of antagonistic activity of bacteria against phytopathogenic fungi. Thus, B. velezensis BZR 336g and B. velezensis BZR 517 produce a significant set of antifungal metabolites and can be used as strains to produce effective biofungicides.
Influence of Bacillus subtilis strain on abscisic acid content in ABA-deficient barley mutant and its wild type
Authors:   Ufa Institute of Biology – subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, Akhtyamova Z.A. , Arkhipova T.N. ,   Ufa Institute of Biology – subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, Martynenko E.V. ,   Ufa Institute of Biology – subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, Nuzhnaya T.V. ,   Ufa Institute of Biology – subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences,   Institute of Biochemistry and Genetics – subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, Ivanov R.S. ,   Ufa Institute of Biology – subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, Kuzmina L.Yu. ,   Ufa Institute of Biology – subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences
Published: August 2021

The ability to produce phytohormones and influence their metabolism in plants is an important property of rhizosphere bacteria that determines their plant growth promoting effect. Since abscisic acid (ABA) reduces stomatal conductance and increases the ability of tissues to conduct water, maintenance of water balance in lettuce plants on the background of activation of their growth was associated with the accumulation of ABA under the influence of bacteria. The aim of the study is to test the hypothesis that the growth-stimulating effect of bacteria on plants depends on their ability to synthesize the hormone ABA. The plants were grown on a light platform; seedlings were treated with a bacterial suspension simultaneously with planting. The ABA content, the relative water content, the chlorophyll content, the level of non-photochemical quenching, the leaf area and the weight of the shoots were measured. The level of transcripts of the HvNCED1, HvNCED2, and HvCYP707A1 genes responsible for ABA metabolism in barley was assessed using real-time PCR. Comparison of the ABA-deficient mutant of barley and plants of its wild type revealed the stimulation of the growth of plants of both genotypes upon bacterial treatment. The shoot mass and leaf area of the untreated mutant with bacteria were about 30 % less compared to Steptoe. The stimulating effect of bacteria was manifested in an increase in leaf area by 15 % in Steptoe and by 35 % in Az 34; shoot mass – by 18 % and 41 %, respectively. As a result, the phenotype difference between plants of two genotypes decreased. In the deficient mutant, the ABA level increased under the influence of Bacillus subtilis IB-22 more than twice. It was due to the ability of bacteria to produce ABA and reduce the activity of ABA degradation in barley plants. The results obtained in this study indicate that certain bacterial strains are able to increase the level of ABA in plants, compensating for the genetically determined deficiency of this hormone.
УСТОЙЧИВОСТЬ АГРОЦЕНОЗОВ ЯРОВОЙ ПШЕНИЦЫ К СОВРЕМЕННЫМ КЛИМАТИЧЕСКИМ ИЗМЕНЕНИЯМ В ЗЕМЛЕДЕЛИИ СТЕПНОЙ ЗОНЫ ЮЖНОГО УРАЛА
Authors:   Institute of the Steppe of the Ural Branch of the Russian Academy of Sciences – a separate unit of the Federal State Budgetary Scientific Institution “Orenburg Federal Research Center” of the Ural Branch of the Russian Academy of Sciences, Gulyanov Yu.A.
Published: August 2021

The assessment of current meteorological trends is necessary for the scientific justification of measures aimed at stabilizing the gross harvest of food grain under conditions of changing climate. The purpose of the research was to assess the impact of climatic changes on the survival rate and safety of productive spring wheat crops until harvesting on the example of some administrative districts (natural and climatic zones) of the Orenburg region. Data on the average daily air temperatures, precipitation and yield of spring wheat during 2008–2019 obtained from open sources were the objects of the research. The average loss of the harvest area of spring wheat in the region, which amounted to 16.9 % of the sown area, for the analyzed period (2008–2019) was equal to 237,160 hectares per year. Its highest relative values were observed in Akbulaksky (45.7 %), Orenburg (40.0 %) and Dombarovsky (38.2 %) districts. The territories with the largest proportions of unharvested areas are characterized by rather “harsh” hydrothermal conditions. The average values of the Selyaninov Hydrothermal Coefficient (HTC) over twelve years were 0.57 mm/°С, 0.48 mm/°С and 0.42 mm/°С in the central, eastern and southern zone of the region, respectively. In the studied zones, there is a clear increase in the aridity of summer months (the growing seasons of spring wheat), especially in the southern zone, where the moisture conditions are characterized as dry. The strongest inverse relationship between the loss of spring wheat harvesting areas and the amount of precipitation (r = −0.50 – −0.71) is observed for the period September–July. The direct relationship between the loss of spring wheat harvesting areas and the sum of active temperatures is the strongest in the April-June period (r = 0.40–0.59). It coincides with the time of seedlings formation and reproductive organs laying, which are the basis of the future crop. To stabilize the gross grain harvest, it is appropriate to carry out a set of organizational, economic and agrotechnical measures aimed at optimizing the structure of the land fund and adapting agricultural technologies to the changing climate.