bluuebunny/crossref_metadata_2025 huggingface dataset:
Axillary uniportal video-assisted thoracoscopic surgery for bullae is a cosmetically superior approach to primary spontaneous pneumothorax: a case report
Authors: Ma Weijiang , Deng Xiuping , Wen Ming , Yang Limin , Ouyang Xun , Liu Xin , Liu Yin
Published: October 2021

Background

Bulla is a common cause of primary spontaneous pneumothorax. Video-assisted thoracoscopic surgery (VATS) through the lateral chest wall is a common surgical approach and an effective treatment for this condition, but postoperative incision scars affect the aesthetic outcome. VATS via axillary approach can hide the scar in the axilla, and the wound in its natural state is invisible; this greatly improves the cosmetic appearance. To our knowledge, this is the first report of VATS-based bullectomy via the axillary approach in a patient with spontaneous pneumothorax.

Case presentation

A 20-year-old female patient was admitted to the hospital with a 2-day history of chest tightness and chest pain. Plain chest computed tomography showed right spontaneous pneumothorax, lung compression of 75%, and right pulmonary bulla. After complete preoperative examination, VATS bullectomy via right axillary approach was performed. During the operation, a bulla measuring about 4 × 4 cm was found at the apex of the right lung and resected. The incision healed well, and the patient was discharged after surgery.

Conclusions

VATS bullectomy via axillary approach is safe and feasible, with the incision hidden in the axilla and not visible in the natural state. This method leaves no scar on the chest wall and has good cosmetic outcome.
A multicenter cross-sectional French study of the impact of COVID-19 on neuromuscular diseases
Authors: Pisella Lucie Isoline , Fernandes Sara , Solé Guilhem , Stojkovic Tanya , Tard Céline , Chanson Jean-Baptiste , Bouhour Françoise , Salort-Campana Emmanuelle , Beaudonnet Guillemette , Debergé Louise , Duval Fanny , Grapperon Aude-Marie , Masingue Marion , Nadaj-Pakleza Aleksandra , Péréon Yann , Audic Frédérique , Behin Anthony , Friedman Diane , Magot Armelle , Noury Jean-Baptiste , Souvannanorath Sarah , Wahbi Karim , Antoine Jean-Christophe , Bigaut Kévin , Camdessanché Jean-Philippe , Cintas Pascal , Debs Rabab , Espil-Taris Caroline , Kremer Laurent , Kuntzer Thierry , Laforêt Pascal , Laugel Vincent , Mallaret Martial , Michaud Maud , Nollet Sylvain , Svahn Juliette , Vicart Savine , Villar-Quiles Rocio Nur , Desguerre Isabelle , Adams David , Segovia-Kueny Sandrine , Merret Géraldine , Hammouda Elhadi , Molon Annamaria , Attarian Shahram
Published: October 2021

Background

Due to their health condition, patients with neuromuscular diseases (NMD) are at greater risk of developing serious complications with COVID-19. The objective of this study was to analyze the prevalence of COVID-19 among NMD patients and the risk factors for its impact and severity during the first wave of the pandemic. Clinical data were collected from NMD-COVID-19 patients, between March 25, 2020 and May 11, 2020 in an anonymous survey carried out by expert physicians from the French Health Care Network Filnemus.

Results

Physicians reported 84 patients, including: 34 with myasthenia gravis, 27 with myopathy and 23 with neuropathy. COVID-19 had no effect on NMD for 48 (58%) patients and 48 (58%) patients developed low COVID-19 severity. COVID-19 caused the death of 9 (11%) NMD patients. Diabetic patients were at greater risk of dying. Patients with diabetes, hypertension or severe forms of NMD had a higher risk of developing a moderate or severe form of COVID-19. In our cohort, corticosteroids and other immunosuppressants were not significantly associated with higher COVID-19 severity for acquired NMD.

Conclusion

During this period, a small percentage of French NMD patients was affected by COVID-19 compared to the general French population and COVID-19 had a limited short-term effect on them. Diabetes, hypertension and a severe degree of NMD were identified as risk factors of unfavorable outcome following COVID-19. Conversely, in our cohort of patients with acquired NMD, corticosteroids or other immunosuppressants did not appear to be risk factors for more severe COVID-19.
The impact of deep versus standard neuromuscular block on intraoperative safety during laparoscopic surgery: an international multicenter randomized controlled double-blind strategy trial — EURO-RELAX TRIAL
Authors: Honing Maarten , Reijnders-Boerboom Gabby , Dell-Kuster Salome , van Velzen Monique , Martini Chris , Valenza Franco , Proto Paolo , Cambronero Oscar Díaz , Broens Suzanne , Panhuizen Ivo , Roozekrans Margot , Fuchs-Buder Thomas , Boon Martijn , Dahan Albert , Warlé Michiel
Published: October 2021

Background

Muscle relaxants are routinely used during anesthesia to facilitate endotracheal intubation and to optimize surgical conditions. However, controversy remains about the required depth of neuromuscular block (NMB) needed for optimal surgical working conditions and how this relates to other outcomes. For instance, a deep neuromuscular block yields superior surgical working conditions compared to a standard NMB in laparoscopic surgery, however, a robust association to other (safety) outcomes has not yet been established.

Methods

Trial design: an international multicenter randomized controlled double-blind strategy trial.

Trial population: 922 patients planned for elective, laparoscopic or robotic, abdominal surgery.

Intervention: Patients will be randomized to a deep NMB (post-tetanic count 1–2 twitches) or standard care (single-dose muscle relaxant administration at induction and repeated only if warranted by surgical team).

Main trial endpoints: Primary endpoint is the difference in incidence of intraoperative adverse events during laparoscopic surgery graded according to ClassIntra® classification (i.e., ClassIntra® grade ≥ 2) between both groups. Secondary endpoints include the surgical working conditions, 30-day postoperative complications, and patients’ quality of recovery.

Discussion

This trial was designed to analyze the effect of deep neuromuscular block compared to standard neuromuscular block on intra- and postoperative adverse events in patients undergoing laparoscopic surgery.

Trial registration

ClinicalTrials.gov NCT04124757(EURO-RELAX); registration URL: https://clinicaltrials.gov/ct2/show/NCT04124757, registered on October 11th, 2019.
The current status, challenges and prospects of using biomass energy in Ethiopia
Authors: Benti Natei Ermias , Gurmesa Gamachis Sakata , Argaw Tegenu , Aneseyee Abreham Berta , Gunta Solomon , Kassahun Gashaw Beyene , Aga Genene Shiferaw , Asfaw Ashenafi Abebe
Published: October 2021

Despite enormous challenges in accessing sustainable energy supplies and advanced energy technologies, Ethiopia has one of the world's fastest growing economies. The development of renewable energy technology and the building of a green legacy in the country are being prioritized. The total installed capacity for electricity generation in Ethiopia is 4324.3 MW as on October, 2018. Renewable energy accounts for 96.5% of total generation; however, despite the county's enormous biomass energy potential, only 0.58% of power is generated using biomass. Ethiopia has surplus woody biomass, crop residue and animal dung resources which comprise about 141.8 million metric tons of biomass availability per year. At present the exploited potential is about 71.9 million metric tons per year. This review paper provides an in-depth assessment of Ethiopia's biomass energy availability, potential, challenges, and prospects. The findings show that, despite Ethiopia's vast biomass resource potential, the current use of modern energy from biomass is still limited. As a result, this study supports the use of biomass-based alternative energy sources without having a negative impact on the socioeconomic system or jeopardizing food security or the environment. This finding also shows the challenges, opportunities and possible solutions to tackle the problem to expand alternative energy sources. The most effective techniques for producing and utilizing alternate energy sources were also explored. Moreover, some perspectives are given based on the challenges of using efficient energy production and sustainable uses of biomass energy in Ethiopia as it could be also implemented in other developing countries. We believe that the information in this review will shed light on the current and future prospects of biomass energy deployment in Ethiopia.
The methylome of Biomphalaria glabrata and other mollusks: enduring modification of epigenetic landscape and phenotypic traits by a new DNA methylation inhibitor
Authors: Luviano Nelia , Lopez Marie , Gawehns Fleur , Chaparro Cristian , Arimondo Paola B. , Ivanovic Slavica , David Patrice , Verhoeven Koen , Cosseau Céline , Grunau Christoph
Published: October 2021

Background

5-Methylcytosine (5mC) is an important epigenetic mark in eukaryotes. Little information about its role exists for invertebrates. To investigate the contribution of 5mC to phenotypic variation in invertebrates, alteration of methylation patterns needs to be produced. Here, we apply new non-nucleoside DNA methyltransferase inhibitors (DNMTi) to introduce aleatory changes into the methylome of mollusk species.

Results

Flavanone inhibitor Flv1 was efficient in reducing 5mC in the freshwater snails Biomphalaria glabrata and Physa acuta, and to a lesser degree, probably due to lower stability in sea water, in the oyster Crassostrea gigas. Flv1 has no toxic effects and significantly decreased the 5mC level in the treated B. glabrata and in its offspring. Drug treatment triggers significant variation in the shell height in both generations. A reduced representation bisulfite-sequencing method called epiGBS corroborates hypomethylation effect of Flv1 in both B. glabrata generations and identifies seven Differential Methylated Regions (DMR) out of 32 found both in Flv1-exposed snails and its progeny, from which 5 were hypomethylated, demonstrating a multigenerational effect. By targeted bisulfite sequencing, we confirmed hypomethylation in a locus and show that it is associated with reduced gene expression.

Conclusions

Flv1 is a new and efficient DNMTi that can be used to induce transient and heritable modifications of the epigenetic landscape and phenotypic traits in mollusks, a phylum of the invertebrates in which epigenetics is understudied.
Identification and drug-induced reversion of molecular signatures of Alzheimer’s disease onset and progression in AppNL-G-F, AppNL-F, and 3xTg-AD mouse models
Authors: Pauls Eduardo , Bayod Sergi , Mateo Lídia , Alcalde Víctor , Juan-Blanco Teresa , Sánchez-Soto Marta , Saido Takaomi C. , Saito Takashi , Berrenguer-Llergo Antoni , Attolini Camille Stephan-Otto , Gay Marina , de Oliveira Eliandre , Duran-Frigola Miquel , Aloy Patrick
Published: October 2021

Background

In spite of many years of research, our understanding of the molecular bases of Alzheimer’s disease (AD) is still incomplete, and the medical treatments available mainly target the disease symptoms and are hardly effective. Indeed, the modulation of a single target (e.g., β-secretase) has proven to be insufficient to significantly alter the physiopathology of the disease, and we should therefore move from gene-centric to systemic therapeutic strategies, where AD-related changes are modulated globally.

Methods

Here we present the complete characterization of three murine models of AD at different stages of the disease (i.e., onset, progression and advanced). We combined the cognitive assessment of these mice with histological analyses and full transcriptional and protein quantification profiling of the hippocampus. Additionally, we derived specific Aβ-related molecular AD signatures and looked for drugs able to globally revert them.

Results

We found that AD models show accelerated aging and that factors specifically associated with Aβ pathology are involved. We discovered a few proteins whose abundance increases with AD progression, while the corresponding transcript levels remain stable, and showed that at least two of them (i.e., lfit3 and Syt11) co-localize with Aβ plaques in the brain. Finally, we found two NSAIDs (dexketoprofen and etodolac) and two anti-hypertensives (penbutolol and bendroflumethiazide) that overturn the cognitive impairment in AD mice while reducing Aβ plaques in the hippocampus and partially restoring the physiological levels of AD signature genes to wild-type levels.

Conclusions

The characterization of three AD mouse models at different disease stages provides an unprecedented view of AD pathology and how this differs from physiological aging. Moreover, our computational strategy to chemically revert AD signatures has shown that NSAID and anti-hypertensive drugs may still have an opportunity as anti-AD agents, challenging previous reports.
The protein-protein interaction between connective tissue growth factor and annexin A2 is relevant to pannus formation in rheumatoid arthritis
Authors: Yin Guoyu , Yang Chenglin , Wu Gan , Yu Xinxin , Tian Qingqing , Chen Daoxing , Cao Ben , Zhao Lin , Xu Nannan , Jin Shengwei , Zhang Wei , Wang Jianguang
Published: October 2021

Background

Connective tissue growth factor (CTGF)-induced angiogenesis is a crucial factor in rheumatoid arthritis (RA), but CTGF-interacting protein and related molecular mechanism of their interaction have not been fully elucidated.

Methods

CTGF-interacting proteins were identified through the LC-MS/MS analysis of the Co-IP products from fibroblast-like synoviocyte (FLS) lysates, and the interaction between CTGF and annexin A2 (ANXA2) was further confirmed through Co-IP and BiFC assay. The binding domain, mutant, mechanism, and angiogenesis function were assessed by homology modeling, molecular docking, MTT, cell scratch, tube formation, and chick chorioallantoic membrane (CAM) assays. Additionally, severe combined immunodeficiency (SCID) mouse co-implantation model was constructed to confirm the effect of ANXA2/CTGF-TSP1 in the process of RA in vivo.

Results

ANXA2 was identified and verified as an interaction partner of CTGF for the first time by Co-IP and LC-MS/MS analysis. Co-localization of CTGF and ANXA2 was observed in RA-FLS, and direct interaction of the TSP-1 domain of CTGF and ANXA2 was determined in HEK293T cells. The spatial conformation and stable combination of the ANXA2/CTGF-TSP1 complex were assessed by homology modeling in the biomimetic environment. The function of the ANXA2/CTGF-TSP1 complex was proved on promoting FLS proliferation, migration, and angiogenesis in vitro and deteriorating FLS invasion and joint damage in SCID mice.

Conclusions

TSP-1 is the essential domain in CTGF/ANXA2 interaction and contributes to FLS migration and pannus formation, inducing the process of RA.
Galectin-3, metalloproteinase-2 and cardiovascular disease were independently associated with metalloproteinase-14 in patients with type 1 diabetes: a cross sectional study
Authors: Melin Eva Olga , Dereke Jonatan , Hillman Magnus
Published: October 2021

Background

Type 1 diabetes (T1D) is a major risk factor for cardiovascular disease (CVD). Matrix metalloproteinase-14 (MMP-14) is involved in the development of atherosclerosis and CVD. The main aim was to explore the associations between MMP-14 and selected inflammatory and metabolic variables, CVD, depression, physical activity, smoking and medication in patients with T1D. The secondary aim was to explore associations with CVD.

Methods

Cross-sectional design. The participants were consecutively recruited from one specialist diabetes out-patient clinic. Depression was assessed by a self-report instrument. Blood samples, anthropometrics and blood pressure were collected, supplemented with data from electronic health records. High MMP-14 was defined as  ≥  5.81 ng/mL. Non-parametric tests, Chi2tests and multiple logistic regression analyses were performed.

Results

Two hundred and sixty-eighth T1D patients aged 18–59 years participated (men 58%, high MMP-14 25%, CVD 3%). Sixty-seven patients with high MMP-14, compared to 201 patients with lower MMP-14, had higher prevalence of CVD (8% versus 1%,p  =  0.012), and had higher levels of galectin-3 (p <  0.001) and MMP-2 (p =  0.018). Seven patients with CVD, compared to 261 without, were older (p  =  0.003), had longer diabetes duration (p  =  0.027), and had higher prevalence of high MMP-14 (71% versus 24%,p  =  0.012), abdominal obesity (p  =  0.014), depression (p =  0.022), usage of antidepressants (p  =  0.008), antihypertensive drugs (p  =  0.037) and statins (p  =  0.049).

Galectin-3 (per ng/mL) [adjusted odds ratio (AOR) 2.19,p  <  0.001], CVD (AOR 8.1,p  =  0.027), and MMP-2 (per ng/mL) (AOR 1.01,p =  0.044) were associated with high MMP-14. Depression (AOR 17.4,p =  0.006), abdominal obesity (15.8,p  =  0.006), high MMP-14 (AOR 14.2,p  =  0.008), and diabetes duration (AOR 1.10,p  =  0.012) were associated with CVD.

Conclusions

The main findings of this study were that galecin-3, MMP-2, and CVD were independently associated with high levels of MMP-14 in T1D patients. The association between MMP-14 and galectin-3 is a new finding. No traditional risk factors for CVD were associated with MMP-14. Depression, abdominal obesity and MMP-14 were independently associated with CVD.
Microbial analysis and virulence genes detection of milk preserved using heat-assisted pulsed electric field
Authors: Yuliangsih Suci , Waturangi Diana Elizabeth , Yogiara
Published: October 2021

Objective

Microbial analysis in milk preserved using heat-assisted Pulsed Electric Field (PEF) need to be assessed. In this study we analyze the microbial quality and virulence-associated genes in milk samples preserved using heat-assisted PEF from several producers in Indonesia.

Results

Milk samples were collected consisting of raw milk, milks taken after the heating, PEF, mixing, cooling, and packaging. Microbiological and Polymerase Chain Reaction (PCR) detection for virulence genes were performed. Heat-assisted PEF treatment gave 2.7–7.47 log reduction for TPC; 1.6–2.56 log reduction for MPN number; 3.13–6.48 log reduction for S. aureus; and for B. cereus there was an increase of 0.76 log and a reduction of 0.46 log. While milk samples from thermal pasteurization gave log reduction numbers of TPC, MPN, and S. aureus respectively 5.28; 2.56; and 4.73, for B. cereus was increasing 2.4 log. Producer C performed the best results with significant reduction compared with others (p < 0.005). There were no colonies of L. monocytogenes found in all of the samples. PCR results showed that milk samples possessed virulence genes 17.5% (10/57) of invA genes, 54.4% (31/57) of nheA genes, 68.4% (39/57) of cytK genes, 38.6% (22/57) of nuc genes, 63.2% (36/57) of ileS genes, while hly and actA genes were not detected.
Supplementation of Lactobacillus casei reduces the mortality of Bombyx mori larvae challenged by Nosema bombycis
Authors: Suraporn Siripuk , Terenius Olle
Published: October 2021

Objective

Pebrine, caused by the microsporidium Nosema bombycis, is one of the severe diseases in Thai polyvoltine strains of the silkworm Bombyx mori. Studies showing the presence of Lactobacillus species in the silkworm gut, where the Nosema parasites enter, suggests that these bacteria may have a protective effect. The aim of this study was to investigate the effect of supplementation of Lactobacillus casei on the survival ratio of silkworm larvae challenged with N. bombycis.

Results

A group of silkworm larvae of the commercial Thai polyvoltine hybrid strain DokBua was supplemented with L. casei on the second day of the 2nd, 3rd, 4th, and 5th instar. When a control group of silkworm larvae were challenged with N. bombycis on the second day of the 4th instar, the survival rate was 68%, but it was 91% for larvae supplemented with L. casei. For those larvae that survived the treatments until pupation, we determined the growth characters larval weight, cocooning ratio, and pupation ratio, and the economic characters cocoon weight and cocoon shell weight. When infected with N. Bombycis, growth characters were significantly higher in larvae also receiving L. casei.
Validating biomarkers and models for epigenetic inference of alcohol consumption from blood
Authors: Maas Silvana C. E. , Vidaki Athina , Teumer Alexander , Costeira Ricardo , Wilson Rory , van Dongen Jenny , Beekman Marian , Völker Uwe , Grabe Hans J. , Kunze Sonja , Ladwig Karl-Heinz , van Meurs Joyce B. J. , Uitterlinden André G. , Voortman Trudy , Boomsma Dorret I. , Slagboom P. Eline , van Heemst Diana , van der Kallen Carla J. H. , van den Berg Leonard H. , Waldenberger Melanie , Völzke Henry , Peters Annette , Bell Jordana T. , Ikram M. Arfan , Ghanbari Mohsen , Kayser Manfred
Published: October 2021

Background

Information on long-term alcohol consumption is relevant for medical and public health research, disease therapy, and other areas. Recently, DNA methylation-based inference of alcohol consumption from blood was reported with high accuracy, but these results were based on employing the same dataset for model training and testing, which can lead to accuracy overestimation. Moreover, only subsets of alcohol consumption categories were used, which makes it impossible to extrapolate such models to the general population. By using data from eight population-based European cohorts (N = 4677), we internally and externally validated the previously reported biomarkers and models for epigenetic inference of alcohol consumption from blood and developed new models comprising all data from all categories.

Results

By employing data from six European cohorts (N = 2883), we empirically tested the reproducibility of the previously suggested biomarkers and prediction models via ten-fold internal cross-validation. In contrast to previous findings, all seven models based on 144-CpGs yielded lower mean AUCs compared to the models with less CpGs. For instance, the 144-CpG heavy versus non-drinkers model gave an AUC of 0.78 ± 0.06, while the 5 and 23 CpG models achieved 0.83 ± 0.05, respectively. The transportability of the models was empirically tested via external validation in three independent European cohorts (N = 1794), revealing high AUC variance between datasets within models. For instance, the 144-CpG heavy versus non-drinkers model yielded AUCs ranging from 0.60 to 0.84 between datasets. The newly developed models that considered data from all categories showed low AUCs but gave low AUC variation in the external validation. For instance, the 144-CpG heavy and at-risk versus light and non-drinkers model achieved AUCs of 0.67 ± 0.02 in the internal cross-validation and 0.61–0.66 in the external validation datasets.

Conclusions

The outcomes of our internal and external validation demonstrate that the previously reported prediction models suffer from both overfitting and accuracy overestimation. Our results show that the previously proposed biomarkers are not yet sufficient for accurate and robust inference of alcohol consumption from blood. Overall, our findings imply that DNA methylation prediction biomarkers and models need to be improved considerably before epigenetic inference of alcohol consumption from blood can be considered for practical applications.
Successful treatment with radiation therapy for desmoid-type fibromatosis with unilateral hydronephrosis: a case report
Authors: Ishikawa Yojiro , Umezawa Rei , Yamamoto Takaya , Takahashi Noriyoshi , Takeda Kazuya , Suzuki Yu , Jingu Keiichi
Published: October 2021

Background

Desmoid-type fibromatosis is a rare disease that can result in hydronephrosis. Hydronephrosis associated with desmoid-type fibromatosis often requires surgery or ureteral stent insertion. Although radiation therapy is recommended for inoperable cases of desmoid-type fibromatosis, there has been no report of treatment for hydronephrosis associated with desmoid-type fibromatosis by radiation therapy alone. We herein report a case of successful treatment for inoperable recurrence of desmoid-type fibromatosis with unilateral hydronephrosis by radiation therapy alone.

Case presentation

A 43-year-old Japanese female underwent resection of desmoid-type fibromatosis in the right inguinal region and combined resection of the right external iliac vein 5 years before. Other treatment was not performed because of her pregnancy. Four years after surgery, desmoid-type fibromatosis recurred in the right pelvic wall. Cyclooxygenase-2 selective inhibitor treatment was given for 1 year, but her desmoid-type fibromatosis enlarged to more than 10 cm, and she had swelling of her right leg and hydronephrosis of her right kidney. The patient received 50.4 Gy in 28 fractions of prophylactic irradiation using 10 MV X-ray and 9 Gy in five fractions of a sequential boost for the recurrent desmoid-type fibromatosis. Although there was temporary tumor progression at 1 month after radiation therapy, slow regression of the tumor was seen. At 5 years after radiation therapy, there was no disease progression or severe complications.

Conclusion

We experienced successful treatment for an inoperable case of desmoid-type fibromatosis with hydronephrosis. Moderate-dose radiation therapy alone is an effective and feasible approach for the management of hydronephrosis associated with desmoid-type fibromatosis.
RETRACTED ARTICLE: Secretome of endothelial progenitor cells from stroke patients promotes endothelial barrier tightness and protects against hypoxia-induced vascular leakage
Authors: Loiola Rodrigo Azevedo , García-Gabilondo Miguel , Grayston Alba , Bugno Paulina , Kowalska Agnieszka , Duban-Deweer Sophie , Rizzi Eleonora , Hachani Johan , Sano Yasuteru , Shimizu Fumitaka , Kanda Takashi , Mysiorek Caroline , Mazurek Maciej Piotr , Rosell Anna , Gosselet Fabien
Published: October 2021

Background

Cell-based therapeutic strategies have been proposed as an alternative for brain repair after stroke, but their clinical application has been hampered by potential adverse effects in the long term. The present study was designed to test the effect of the secretome of endothelial progenitor cells (EPCs) from stroke patients (scCM) on in vitro human models of angiogenesis and vascular barrier.

Methods

Two different scCM batches were analysed by mass spectrometry and a proteome profiler. Human primary CD34+-derived endothelial cells (CD34+-ECs) were used for designing angiogenesis studies (proliferation, migration, and tubulogenesis) or in vitro models of EC monolayer (confluent monolayer ECs—CMECs) and blood–brain barrier (BBB; brain-like ECs—BLECs). Cells were treated with scCM (5 μg/mL) or protein-free endothelial basal medium (scEBM—control). CMECs or BLECs were exposed (6 h) to oxygen–glucose deprivation (OGD) conditions (1% oxygen and glucose-free medium) or normoxia (control—5% oxygen, 1 g/L of glucose) and treated with scCM or scEBM during reoxygenation (24 h).

Results

The analysis of different scCM batches showed a good reproducibility in terms of protein yield and composition. scCM increased CD34+-EC proliferation, tubulogenesis, and migration compared to the control (scEBM). The proteomic analysis of scCM revealed the presence of growth factors and molecules modulating cell metabolism and inflammatory pathways. Further, scCM decreased the permeability of CMECs and upregulated the expression of the junctional proteins such as occludin, VE-cadherin, and ZO-1. Such effects were possibly mediated through the activation of the interferon pathway and a moderate downregulation of Wnt signalling. Furthermore, OGD increased the permeability of both CMECs and BLECs, while scCM prevented the OGD-induced vascular leakage in both models. These effects were possibly mediated through the upregulation of junctional proteins and the regulation of MAPK/VEGFR2 activity.

Conclusion

Our results suggest that scCM promotes angiogenesis and the maturation of newly formed vessels while restoring the BBB function in ischemic conditions. In conclusion, our results highlight the possibility of using EPC-secretome as a therapeutic alternative to promote brain angiogenesis and protect from ischemia-induced vascular leakage.
Decoding antibacterial and antibiofilm properties of cinnamon and cardamom essential oils: a combined molecular docking and experimental study
Authors: Pourkhosravani Elahe , Dehghan Nayeri Fatemeh , Mohammadi Bazargani Mitra
Published: October 2021

This study sets out to compare the antibacterial and antibiofilm profiles of Ci/Ca EOs alone and in combination together against infectious bacterial strains. MIC assay was carried out to survey the effectiveness of prepared EOs by two-fold serial dilution method and MTT evaluation. Synergic antibacterial properties of EOs against target strains were studied by using checkerboard titration method. Biofilm growth and development were evaluated using CV and XTT reduction assays. Antibacterial activity was observed for EOs against both bacterial strains with stronger activity for CiEO against both bacteria. The synergistic antibacterial effect was observed only against B. subtilis. Based on the FIC index, combinations could not inhibit the growth of E. coli. The pure EOs and their combination inhibited cell attachment for both studied bacteria with stronger effect on E. coli. CV and XTT reduction assays results showed that Ci EO and its combination with CaEO had the highest antibiofilm activity at lowest MIC value 0.08% and 0.04/0.02% against biofilm formed by E. coli and B. subtilis respectively, indicating a high antibiofilm potential. Computational docking analyses also postulated that the active constituents of evaluated EOs have the potential to interact with different bacterial targets, suggested binding mode of action of EOs metabolites. By and large, synergistic anti-biofilm properties of EOs may provide further options for developing novel formula to inhibit a variety of infectious clinical and industrial strains without (or less) toxicity effects on human body.

Graphical Abstract
Efficacy and safety of IL-6 inhibitors in patients with COVID-19 pneumonia: a systematic review and meta-analysis of multicentre, randomized trials
Authors: Belletti Alessandro , Campochiaro Corrado , Marmiere Marilena , Likhvantsev Valery , Yavorovskiy Andrey , Dagna Lorenzo , Landoni Giovanni , Zangrillo Alberto , Hajjar Ludhmila Abrahão
Published: October 2021

Purpose

COVID-19 is characterized by dysregulated immune response, respiratory failure and a relevant mortality rate among hospitalized patients. Interleukin-6 (IL-6) is involved in COVID-19-associated cytokine storm, and several trials investigated whether its inhibition could improve patients’ outcome. We performed a meta-analysis of randomized trials (RCT) to test this hypothesis.

Materials and methods

Two independent investigators searched PubMed, Scopus, ClnicalTrials.gov and medRxiv up to September 1st, 2021. Inclusion criteria were: administration of tocilizumab or sarilumab; COVID-19 adult patients with pneumonia; and being a RCT. Primary outcome was mortality at the longest follow-up. Secondary outcomes included intubation rate and incidence of adverse events. Two independent investigators extracted data from eligible trials.

Results

Of the 763 studies assessed, 15 RCTs were included (9,320 patients), all were multicentre, and the majority open-label vs standard treatment. IL-6 inhibitors were associated with reduced all-cause mortality at the longest follow-up (1315/5,380 [24.4%] in the IL-6 inhibitors group versus 1080/3,814 [28.3%] in the control group, RR = 0.90; 95% CI 0.84 to 0.96; p for effect = 0.003, I2 = 0%, with 13 studies included), with reduction in 28/30-day mortality and intubation rates, and with no increase in adverse events and secondary infections.

Conclusion

IL-6 inhibitors reduced longest follow-up mortality and intubation in COVID-19 patients. Findings need to be confirmed in high-quality RCTs.
Influence of citrate buffer and flash heating in enhancing the sensitivity of ratiometric genosensing of Hepatitis C virus using plasmonic gold nanoparticles
Authors: Prakash Hrishikesh Shashi , Maroju Pranay Amruth , Boppudi Naga Sai Sriteja , Balapure Aniket , Ganesan Ramakrishnan , Ray Dutta Jayati
Published: October 2021

Gold nanoparticles (Au NPs) based technology has been shown to possess enormous potential in the viral nucleic acid diagnosis. Despite significant advancement in this domain, the existing literature reveals the diversity in the conditions employed for hybridization and tagging of thiolated nucleic acid probes over the Au NPs. Here we employ the probe sequence derived from the Hepatitis C virus to identify the optimal hybridization and thiol-Au NP tagging conditions. In a typical polymerase chain reaction, the probes are initially subjected to flash heating at elevated temperatures to obtain efficient annealing. Motivated by this, in the current study, the hybridization between the target and the antisense oligonucleotide (ASO) has been studied at 65 °C with and without employing flash heating at temperatures from 75 to 95 °C. Besides, the efficiency of the thiolated ASO’s tagging over the Au NPs with and without citrate buffer has been explored. The study has revealed the beneficial role of flash heating at 95 °C for efficient hybridization and the presence of citrate buffer for rapid and effective thiol tagging over the Au NPs. The combinatorial effect of these conditions has been found to be advantageous in enhancing the sensitivity of ratiometric genosensing using Au NPs.
Bioactive compounds from an endophytic fungi Nigrospora aurantiaca
Authors: Safwan Safwan , Hsiao George , Lee Tzong-Huei , Lee Ching-Kuo
Published: October 2021

Background

Many groups of fungi live as an endophyte in plants. Both published and undiscovered bioactive compounds can be found in endophytic fungi. Various biological activities of bioactive compounds from endophytic fungi had been reported, including anti-inflammatory and anticancerous effects.

The chemical investigation of biologically active compounds from endophytic fungi Melaleuca leucadendra Linn. have not yet been stated.

Results

One new compound, namely nigaurdiol (1), along with five known compounds, xyloketal K (2), bostrycin (3), deoxybostrycin (4), xylanthraquinone (5), and ergosterol (6), were isolated from the Melaleuca leucadendra Linn. associated fungal strain Nigrospora aurantiaca#TMU062. Their chemical structures were elucidated by spectroscopic data and compared with literature. All isolated compounds were evaluated for inhibitory effect of NO production in LPS-activated microglial BV-2 cells.

Conclusions

Compound 6 exhibited considerable inhibitory effect on NO production with IC50 values of 7.2 ± 1.4 µM and the survival rate of the cells was 90.8 ± 6.7% at the concentration of 10 µM.
Cerebral autoregulation in anoxic brain injury patients treated with targeted temperature management
Authors: Crippa Ilaria Alice , Vincent Jean-Louis , Zama Cavicchi Federica , Pozzebon Selene , Annoni Filippo , Cotoia Antonella , Njimi Hassane , Gaspard Nicolas , Creteur Jacques , Taccone Fabio Silvio
Published: October 2021

Background

Little is known about the prevalence of altered CAR in anoxic brain injury and the association with patients’ outcome. We aimed at investigating CAR in cardiac arrest survivors treated by targeted temperature management and its association to outcome.

Methods

Retrospective analysis of prospectively collected data. Inclusion criteria: adult cardiac arrest survivors treated by targeted temperature management (TTM). Exclusion criteria: trauma; sepsis, intoxication; acute intra-cranial disease; history of supra-aortic vascular disease; severe hemodynamic instability; cardiac output mechanical support; arterial carbon dioxide partial pressure (PaCO2) > 60 mmHg; arrhythmias; lack of acoustic window. Middle cerebral artery flow velocitiy (FV) was assessed by transcranial Doppler (TCD) once during hypothermia (HT) and once during normothermia (NT). FV and blood pressure (BP) were recorded simultaneously and Mxa calculated (MATLAB). Mxa is the Pearson correlation coefficient between FV and BP. Mxa > 0.3 defined altered CAR. Survival was assessed at hospital discharge. Cerebral Performance Category (CPC) 3–5 assessed 3 months after CA defined unfavorable neurological outcome (UO).

Results

We included 50 patients (Jan 2015–Dec 2018). All patients had out-of-hospital cardiac arrest, 24 (48%) had initial shockable rhythm. Time to return of spontaneous circulation was 20 [10–35] min. HT (core body temperature 33.7 [33.2–34] °C) lasted for 24 [23–28] h, followed by rewarming and NT (core body temperature: 36.9 [36.6–37.4] °C). Thirty-one (62%) patients did not survive at hospital discharge and 36 (72%) had UO. Mxa was lower during HT than during NT (0.33 [0.11–0.58] vs. 0.58 [0.30–0.83]; p = 0.03). During HT, Mxa did not differ between outcome groups. During NT, Mxa was higher in patients with UO than others (0.63 [0.43–0.83] vs. 0.31 [− 0.01–0.67]; p = 0.03). Mxa differed among CPC values at NT (p = 0.03). Specifically, CPC 2 group had lower Mxa than CPC 3 and 5 groups. At multivariate analysis, initial non-shockable rhythm, high Mxa during NT and highly malignant electroencephalography pattern (HMp) were associated with in-hospital mortality; high Mxa during NT and HMp were associated with UO.

Conclusions

CAR is frequently altered in cardiac arrest survivors treated by TTM. Altered CAR during normothermia was independently associated with poor outcome.
Potential of megathrust earthquakes along the southern Ryukyu Trench inferred from GNSS data
Authors: Kano Masayuki , Ikeuchi Aoi , Nishimura Takuya , Miyazaki Shin’ichi , Matsushima Takeshi
Published: October 2021

The southern part of the Ryukyu subduction zone has recorded tsunami events with a recurrence interval of several hundred years. Although their source is controversial, one model suggests that the last 1771 Yaeyama tsunami was caused by a shallow megathrust earthquake with a magnitude of 8. However, the current knowledge on interplate coupling based on recent geodetic data is limited. Here, a time series of Global Navigation Satellite System data from January 2010 to February 2021 was analyzed, including newly installed stations by Kyoto and Kyushu Universities, to obtain the distance changes between stations and vertical secular velocities. The distance changes ranged from 2.4 mm/year in contraction and to 4.7 mm/year in extension, and the vertical velocities exhibited no clear uplift or subsidence, with − 2.4 to 1.1 mm/year. The back slip inversion results indicated a slip deficit of 17–47 mm/year to the south of the Yaeyama Islands. The large slip deficit area is complementarily intervened between the shallower source area of low-frequency earthquakes and the deeper slow slip region, suggesting the spatial heterogeneity of frictional properties along the plate interface. If the large slip deficit area accumulates stress in the same rate since the last 1771 earthquake, it could result in a megathrust event with a moment magnitude greater than 7.5. Because the limited onshore data cannot resolve the slip deficit on the shallow plate interface, seafloor geodetic observations are essential to clarify the detailed spatial distribution of the slip deficit and discuss its earthquake and tsunami potential.

Graphical Abstract
The SREBP (Sterol Regulatory Element-Binding Protein) pathway: a regulatory bridge between carotenogenesis and sterol biosynthesis in the carotenogenic yeast Xanthophyllomyces dendrorhous
Authors: Gómez Melissa , Baeza Marcelo , Cifuentes Víctor , Alcaíno Jennifer
Published: October 2021

Xanthophyllomyces dendrorhous is a basidiomycete yeast that naturally produces the red–orange carotenoid astaxanthin, which has remarkable antioxidant properties. The biosynthesis of carotenoids and sterols share some common elements that have been studied in X. dendrorhous. For example, their synthesis requires metabolites derived from the mevalonate pathway and in both specific pathways, cytochrome P450 enzymes are involved that share a single cytochrome P450 reductase, CrtR, which is essential for astaxanthin biosynthesis, but is replaceable for ergosterol biosynthesis. Research on the regulation of carotenoid biosynthesis is still limited in X. dendrorhous; however, it is known that the Sterol Regulatory Element-Binding Protein (SREBP) pathway, which is a conserved regulatory pathway involved in the control of lipid metabolism, also regulates carotenoid production in X. dendrorhous. This review addresses the similarities and differences that have been observed between mammal and fungal SREBP pathways and what it is known about this pathway regarding the regulation of the production of carotenoids and sterols in X. dendrorhous.
Effects of Greater Central Arterial Stiffness on Cardiovagal Baroreflex Sensitivity in Resistance-Trained Men
Authors: Nakamura Nobuhiro , Muraoka Isao
Published: October 2021

Background

Compared with age-matched untrained men, resistance-trained men who have undergone long duration training (> 2 years) at a high frequency (> 5 days/week) may be lower cardiovagal baroreflex sensitivity (BRS) because of central arterial stiffening. Therefore, the purpose of this study was to examine the effect of greater central arterial stiffness in resistance-trained men on cardiovagal BRS in a cross-sectional study to compare resistance-trained men with age-matched untrained men.

Methods

This cross-sectional study included resistance-trained men (n = 20; age: 22 ± 3; body mass index: 26.7 ± 2.2) and age-matched untrained men (control group: n = 20; age: 25 ± 2; body mass index: 23.7 ± 2.4). The β-stiffness index and arterial compliance were assessed at the right carotid artery using a combination of a brightness mode ultrasonography system for the carotid artery diameter and applanation tonometry for the carotid blood pressure. And, the cardiovagal BRS was estimated by the slope of the R–R interval and systolic blood pressure during Phase II and IV of Valsalva maneuver (VM). The participants maintained an expiratory mouth pressure of 40 mmHg for 15 s in the supine position.

Results

The β-Stiffness index was significantly higher in the resistance-trained group than in the control group (5.9 ± 1.4 vs. 4.4 ± 1.0 a.u., P < 0.01). In contrast, the resistance-trained group had significantly lower arterial compliance (0.15 ± 0.05 vs. 0.20 ± 0.04 mm2/mmHg, P < 0.01) and cardiovagal BRS during Phase IV of VM (9.0 ± 2.5 vs. 12.9 ± 5.4 ms/mmHg, P < 0.01) than the control group and. Moreover, cardiovagal BRS during Phase IV of VM was inversely and positively correlated with the β-stiffness index (r = − 0.59, P < 0.01) and arterial compliance (r = 0.64, P < 0.01), respectively.

Conclusion

Resistance-trained group had greater central arterial stiffness and lower cardiovagal BRS Phase IV compared with control group. Moreover, the central arterial stiffening was related to cardiovagal BRS Phase IV. These results suggest that greater central arterial stiffness in resistance-trained men may be associated with lower cardiovagal BRS.

Trial Registration University hospital Medical Information Network (UMIN) in Japan, UMIN000038116. Registered on September 27, 2019.
Isolation and determination of bacterial microbiota of Varroa destructor and isolation of Lysinibacillus sp. from it
Authors: Usta Mehtap
Published: October 2021

Background

The importance of bees for environmental health is known. Within the scope of this importance, it is of great importance to protect the health of bees and to prevent colony extinction. In this context, it is very important to develop effective methods in combating microorganisms, parasitoids, mites and organisms that cause disease or harm in bees. Both use different methods in terms of bee health.

Result

In this study, the possibility of the bacteria isolated from Varroa destructor mite being bioinsecticide was investigated. Accordingly, six bacteria were isolated from the mite. Isolated bacteria were analyzed according to biochemical tests, molecular analysis, optimum growth pH and phylogenetic tree drawn as Pantoea dispersa (GV1), Lysinibacillus macroides (GV3), Bacillus mycoides (GV4), Lysinibacillus fusiformis (GV5), Pseodomonas lutea (GV5), Lysinibacillus varians (GV7). Lysinibacillus sp. The entomopathogenic feature of Lysinibacillus sp. ranked it as the most important species. When the insecticidal properties of bacteria were examined, they were determined as 53, 90, 62, 95, 74 and 83% for GV1, GV3, GV4, GV5, GV6 and GV7, respectively.

Conclusion

Based on these results and literature review, Lysinibacillus sp. species had a high potential to be used as bioinsecticide against V. destructor mite.
How do fire behavior and fuel consumption vary between dormant and early growing season prescribed burns in the southern Appalachian Mountains?
Authors: Vaughan Matthew C. , Hagan Donald L. , Bridges William C. , Dickinson Matthew B. , Coates T. Adam
Published: October 2021

Background

Despite the widespread use of prescribed fire throughout much of the southeastern USA, temporal considerations of fire behavior and its effects often remain unclear. Opportunities to burn within prescriptive meteorological windows vary seasonally and along biogeographical gradients, particularly in mountainous terrain where topography can alter fire behavior. Managers often seek to expand the number of burn days available to accomplish their management objectives, such as hazardous fuel reduction, control of less desired vegetation, and wildlife habitat establishment and maintenance. For this study, we compared prescribed burns conducted in the dormant and early growing seasons in the southern Appalachian Mountains to evaluate how burn outcomes may be affected by environmental factors related to season of burn. The early growing season was defined as the narrow phenological window between bud break and full leaf-out. Proportion of plot area burned, surface fuel consumption, and time-integrated thermocouple heating were quantified and evaluated to determine potential relationships with fuel moisture and topographic and meteorological variables.

Results

Our results suggested that both time-integrated thermocouple heating and its variability were greater in early growing season burns than in dormant season burns. These differences were noted even though fuel consumption did not vary by season of burn. The variability of litter consumption and woody fuelbed height reduction were greater in dormant season burns than in early growing season burns. Warmer air temperatures and lower fuel moisture, interacting with topography, likely contributed to these seasonal differences and resulted in more burn coverage in early growing season burns than in dormant season burns.

Conclusions

Dormant season and early growing season burns in southern Appalachian forests consumed similar amounts of fuel where fire spread. Notwithstanding, warmer conditions in early growing season burns are likely to result in fire spread to parts of the landscape left unburnt in dormant season burns. We conclude that early growing season burns may offer a viable option for furthering the pace and scale of prescribed fire to achieve management objectives.