bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteolytic Landscapes in Gastric Pathology and Cancerogenesis
Authors: Bernegger Sabine , Jarzab Miroslaw , Wessler Silja , Posselt Gernot
Published: February 2022

Gastric cancer is a leading cause of cancer-related death, and a large proportion of cases are inseparably linked to infections with the bacterial pathogen and type I carcinogen Helicobacter pylori. The development of gastric cancer follows a cascade of transformative tissue events in an inflammatory environment. Proteases of host origin as well as H. pylori-derived proteases contribute to disease progression at every stage, from chronic gastritis to gastric cancer. In the present article, we discuss the importance of (metallo-)proteases in colonization, epithelial inflammation, and barrier disruption in tissue transformation, deregulation of cell proliferation and cell death, as well as tumor metastasis and neoangiogenesis. Proteases of the matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase domain-containing protein (ADAM) families, caspases, calpain, and the H. pylori proteases HtrA, Hp1012, and Hp0169 cleave substrates including extracellular matrix molecules, chemokines, and cytokines, as well as their cognate receptors, and thus shape the pathogenic microenvironment. This review aims to summarize the current understanding of how proteases contribute to disease progression in the gastric compartment.
The Diminishment of Novel Endometrial Carcinoma-Derived Stem-like Cells by Targeting Mitochondrial Bioenergetics and MYC
Authors: Helweg Laureen P. , Windmöller Beatrice A. , Burghardt Leonie , Storm Jonathan , Förster Christine , Wethkamp Nils , Wilkens Ludwig , Kaltschmidt Barbara , Banz-Jansen Constanze , Kaltschmidt Christian
Published: February 2022

Cancer stem cells (CSCs) are a small subpopulation of tumor cells harboring properties that include self-renewal, multi-lineage differentiation, tumor reconstitution, drug resistance and invasiveness, making them key players in tumor relapse. In the present paper, we develop new CSC models and analyze the molecular pathways involved in survival to identify targets for the establishment of novel therapies. Endometrial carcinoma-derived stem-like cells (ECSCs) were isolated from carcinogenic gynecological tissue and analyzed regarding their expression of prominent CSC markers. Further, they were treated with the MYC-signaling inhibitor KJ-Pyr-9, chemotherapeutic agent carboplatin and type II diabetes medication metformin. ECSC populations express common CSC markers, such as Prominin-1 and CD44 antigen as well as epithelial-to-mesenchymal transition markers, Twist, Snail and Slug, and exhibit the ability to form free-floating spheres. The inhibition of MYC signaling and treatment with carboplatin as well as metformin significantly reduced the cell survival of ECSC-like cells. Further, treatment with metformin significantly decreased the mitochondrial membrane potential of ECSC-like cells, while the extracellular lactate concentration was increased. The established ECSC-like populations represent promising in vitro models to further study the contribution of ECSCs to endometrial carcinogenesis. Targeting MYC signaling as well as mitochondrial bioenergetics has shown promising results in the diminishment of ECSCs, although molecular signaling pathways need further investigations.
New Insights into the Interaction of Class II Dihydroorotate Dehydrogenases with Ubiquinone in Lipid Bilayers as a Function of Lipid Composition
Authors: Orozco Rodriguez Juan Manuel , Wacklin-Knecht Hanna P. , Clifton Luke A. , Bogojevic Oliver , Leung Anna , Fragneto Giovanna , Knecht Wolfgang
Published: February 2022

The fourth enzymatic reaction in the de novo pyrimidine biosynthesis, the oxidation of dihydroorotate to orotate, is catalyzed by dihydroorotate dehydrogenase (DHODH). Enzymes belonging to the DHODH Class II are membrane-bound proteins that use ubiquinones as their electron acceptors. We have designed this study to understand the interaction of an N-terminally truncated human DHODH (HsΔ29DHODH) and the DHODH from Escherichia coli (EcDHODH) with ubiquinone (Q10) in supported lipid membranes using neutron reflectometry (NR). NR has allowed us to determine in situ, under solution conditions, how the enzymes bind to lipid membranes and to unambiguously resolve the location of Q10. Q10 is exclusively located at the center of all of the lipid bilayers investigated, and upon binding, both of the DHODHs penetrate into the hydrophobic region of the outer lipid leaflet towards the Q10. We therefore show that the interaction between the soluble enzymes and the membrane-embedded Q10 is mediated by enzyme penetration. We can also show that EcDHODH binds more efficiently to the surface of simple bilayers consisting of 1-palmitoyl, 2-oleoyl phosphatidylcholine, and tetraoleoyl cardiolipin than HsΔ29DHODH, but does not penetrate into the lipids to the same degree. Our results also highlight the importance of Q10, as well as lipid composition, on enzyme binding.
Screening of Novel Bioactive Peptides from Goat Casein: In Silico to In Vitro Validation
Authors: Coscueta Ezequiel R. , Batista Patrícia , Gomes José Erick Galindo , da Silva Roberto , Pintado Maria Manuela
Published: February 2022

Food-derived bioactive peptides are of great interest to science and industry due to evolving drivers of food product innovation, including health and wellness. This study aims to draw attention through a critical study on how bioinformatics analysis is employed in the identification of bioactive peptides in the laboratory. An in silico analysis (PeptideRanker, BIOPEP, AHTpin, and mAHTPred) of a list of peptides from goat casein hydrolysate was performed to predict which sequences could potentially be bioactive. To validate the predictions, the in vitro antihypertensive potential of the five peptides with the highest potential was first measured. Then, for three of these, gastrointestinal digestion was simulated in vitro, followed by the analysis of the resulting ACE inhibitory activity as well as antioxidant capacity. We thus observed that the use of new computational biology technologies to predict peptide sequences is an important research tool, but they should not be used alone and complementarity with various in vitro and in vivo assays is essential.
Bioactive Secondary Metabolites from Plant Sources: Types, Synthesis, and Their Therapeutic Uses
Authors: Twaij Baan Munim , Hasan Md. Nazmul
Published: February 2022

Plants are the source of various photochemicals; metabolites are used in medicinal and environmental sectors as well as being widely used in commercial and pharmaceutical products. Although they produce a number of medicinal products, either already on the market or under trial, the amounts obtained from plant sources are very minute or difficult to synthesize at an industrial level due to the complex chemical composition and chirality exhibited by these compounds. However, plant cell cultures offer a good alternative for the consistent production of desired secondary metabolites under the influence of precursors and elicitors. In this review, we discuss the various aspects of secondary metabolites, production synthesis, and sources of medical products from plant sources.
The Postmortem Interval of Two Decedents and Two Dog Carcasses at the Same Scene Based on Forensic Entomology
Authors: Li Liangliang , Wang Yinghui , Liao Mingqing , Zhang Yanan , Kang Chengtao , Hu Gengwang , Guo Yi , Wang Jiangfeng
Published: February 2022

In this paper, we report the estimation of the minimum PMIs of two human corpses and two dog carcasses using entomological evidence. Corpses of an elderly couple and carcasses of four dogs were found scattered on different floors in a house. The scene was very dirty. In addition, there were 12 emaciated live dogs at the scene. The corpses had been eaten by the dogs to different degrees, but the damage was greater on the man’s corpse. After forensic examination, it was concluded that both individuals died of natural causes. The minimum PMIs of the two individuals and the two dogs were estimated using entomological evidence. The minimum PMIs of the other two dogs were not estimated because of the risk of contamination with the human corpses. Different insect species were found on each of the corpses and carcasses. The minimum PMIs were estimated as about 8.75 days for the woman, 4.17 days for the man, 3.13 days for the dog found in the stairwell and about 28.80 days for the dog found in the toilet. These estimations coincided with the time the woman stopped communicating with her daughter and when the electricity consumption at the house decreased significantly.
Risk of Death and Ischemic Stroke in Patients with Atrial Arrhythmia and Thrombus or Sludge in Left Atrial Appendage at One-Year Follow-Up
Authors: Kosmalska Katarzyna , Gilis-Malinowska Natasza , Rzyman Malgorzata , Danilowicz-Szymanowicz Ludmila , Fijalkowski Marcin
Published: February 2022

Thrombus in the left atrial appendage is a contraindication for cardioversion. Sludge is considered similarly as threatening as thrombus; however, the risk of death and ischemic stroke in patients with atrial arrhythmia and thrombus or sludge is not well-known. This study focused on assessing the risk of death and ischemic stroke at one-year follow-up in patients with atrial arrhythmia and thrombus or sludge, as well as the effectiveness of anticoagulation in thrombus resolution. 77 out of 267 (29%) of patients who were scheduled for cardioversion were diagnosed with thrombus or sludge. The annual mortality in patients with thrombus or sludge was 23%. In the group without thrombus, the annual mortality was 1.6%. Overall, 17% of patients with thrombus or sludge experienced ischemic stroke. In patients without thrombus, the risk of stroke was 1%. Sludge increased risk of stroke compared to those without thrombus or sludge by 11% vs. 1%, respectively. No differences in mortality or stroke prevalence were observed between sludge and thrombus. Thrombus or sludge in the LAA have a poor prognosis. A diagnosis of sludge has a similar impact on risk of ischemic strokes as does a diagnosis of thrombus.
Characterization of Conjunctival Sac Microbiome from Patients with Allergic Conjunctivitis
Authors: Song Hang , Xiao Kang , Min Hanyi , Chen Zhengyu , Long Qin
Published: February 2022

Conjunctival sac microbiome alterations have been reported to be closely associated with many ocular diseases. However, the characteristic of conjunctival sac microbiome in allergic conjunctivitis (AC) was scarcely described. In this study, we aimed to identify the differences of the conjunctival sac microbiome composition in AC patients compared with normal controls (NCs) using high-throughput 16S rDNA sequencing metagenomic analysis. The conjunctival sac microbiome samples from 28 AC patients and 39 NC patients were collected. The V3-V4 region of 16S rRNA gene high-throughput sequencing was performed on the illumina MiSeq platform. Alpha diversity, beta diversity and the relative abundance at the phylum and genus levels were analyzed using QIIME. Alpha diversity demonstrated by Chao1, Observed_species and PD_whole_tree indexes did not show significant difference between the AC and NC groups, while the Shannon index was higher in the AC group. Beta diversity showed divergent microbiome composition in different groups (p < 0.005). The top five abundant phyla were Firmicutes, Proteobacteria, Actinobacteriota, Bacteroidota and Cyanobacteria in both groups. The top five abundant genera were Bacillus, Staphylococcus, Corynebacterium, Acinetobacter and Ralstonia in the AC group and Acinetobacter, Staphylococcus, Bacillus, Clostridium_sensu_stricto_1, Corynebacterium and Geobacillus in the NC group. The Firmicutes/Bacteroidetes (F/B) ratio at the phylum level was similar between groups (p = 0.144). The Bacillus/Acinetobacter (B/A) ratio at the genus level was higher in the AC group (p = 0.021). The dysbiosis detected in this study might provide further evidence to investigate the mechanism and treatment methods for allergic conjunctivitis.
Arthroscopy-Assisted Reduction and Internal Fixation versus Open Reduction and Internal Fixation for Glenoid Fracture with Scapular Involvement: A Retrospective Cohort Study
Authors: Lin I-Hao , Lin Tsung-Li , Chang Hao-Wei , Lin Chia-Yu , Tsai Chun-Hao , Lo Chien-Sheng , Chen Hui-Yi , Chen Yi-Wen , Hsu Chin-Jung
Published: February 2022

Background: We investigated the superiority of arthroscopy-assisted reduction and internal fixation (ARIF) to open reduction and internal fixation (ORIF) for treating glenoid fracture with scapular involvement. Methods: We retrospectively enrolled patients with glenoid fracture who underwent ARIF or ORIF from 2010–2020. Radiographic outcomes were assessed, and clinical outcomes (active range of motion [ROM], visual analog scale [VAS], Constant, and Disabilities of the Arm, Shoulder and Hand [DASH]) were evaluated 12 months postoperatively. Results: Forty-four patients with Ideberg type II–VI glenoid fractures (ARIF: 20; ORIF: 24; follow-up 12–22 months) were included. Union was achieved in all patients. Active ROM values were comparable between the approaches. Constant and DASH scores were non-significantly better with ARIF (90.9 ± 9.2 vs. 86.6 ± 18.1 [p = 0.341] and 6.8 ± 9.4 vs. 9.3 ± 21.3 [p = 0.626], respectively). However, VAS scores were significantly lower with ARIF (1.5 ± 0.6 vs. 2.7 ± 1.4, p = 0.001). Associated intra-articular lesions (articular depressions [80%], superior labral anterior-posterior tear [20%], labral tears [30%]) were found in most ARIF cases and were repaired during ARIF. Conclusions: For glenoid fracture with scapular involvement, ARIF allows accurate diagnosis of fracture pattern and the management of associated intra-articular lesions, with better pain control outcomes than ORIF. Thus, arthroscopy-assistant surgery should be considered in patient with glenoid fracture.
New Strategy for the Detection and Treatment of Helicobacter pylori Infections in Primary Care Guided by a Non-Invasive PCR in Stool: Protocol of the French HepyPrim Study
Authors: Pichon Maxime , Freche Bernard , Burucoa Christophe
Published: February 2022

Helicobacter pylori (Hp) infects half of the world population and is responsible for gastric, duodenal ulcers and gastric cancer. The eradication of Hp cures ulcers and prevents ulcer recurrences and gastric cancer. Antibiotic resistance of Hp, and particularly clarithromycin resistance, is the primary cause of treatment failure and is a major concern identified by the WHO as a high priority requiring research into new strategies. Treatments guided by the detection of antibiotic resistance have proven their medical and economical superiority. However, this strategy is severely hampered by the invasive nature of the fibroscopy, since antibiotic resistance detection requires gastric biopsies. The eradication of Hp involves primary care physicians. The objective of this study will be to evaluate the feasibility of a strategy for the management of Hp infection in primary care by a recently developed non-invasive procedure and its non-inferiority in eradication rates compared with the strategy recommended by the French National Authority of Health. The non-invasive procedure is a PCR on stool to detect Hp infection and mutations conferring resistance to clarithromycin allowing a treatment guided by the results of the PCR. We present the protocol of a prospective, multicenter, randomized, controlled interventional study in two arms.
Influence of Obesity and Unemployment on Fertility Rates: A Multinational Analysis of 30 Countries from 1976 to 2014
Authors: König-Castillo Deirdre Maria , Ott Johannes , König Daniel , Hager Marlene , Kahr Maike Katja , Dorffner Georg
Published: February 2022

Background: The rationale of a postulated decrease in fertility rate development is still being debated. Among the multiple influencing factors, socioeconomic variables and their complex influence are of particular interest. Methods: Data on socioeconomic and health variables from 1976–2014 of 30 countries within the OECD region were analysed for their respective influence on fertility rates by using mixed-effect regression models. Results: A significant negative influence of the increase in unemployment rate on the following year’s changes in fertility rate in Western (−0.00256; p < 0.001) as well as Eastern European (−0.0034; p < 0.001) countries was revealed. The effect of being overweight was significant for Western European (−0.00256; p < 0.001) countries only. When analysing the whole OECD region, an increase in unemployment retained its significant negative influence on the fertility rate (−0.0028; p < 0.001), while being overweight did not. Interestingly, divergent influences of time were revealed and fertility rates increased with time in Eastern Europe while they decreased in Western Europe. Conclusion: Importantly, a significant negative influence of increase in unemployment on the fertility rate was revealed—irrespective of the region and time analysed. Furthermore, an adverse effect of being overweight on the fertility rate in Western European countries was revealed. Interestingly, time was associated with a decreasing fertility rate in Western but not in Eastern Europe.
Procalcitonin to Predict Severity of Acute Cholangitis and Need for Urgent Biliary Decompression: Systematic Scoping Review
Authors: Silangcruz Krixie , Nishimura Yoshito , Czech Torrey , Kimura Nobuhiko , Yess James
Published: February 2022

Serum procalcitonin (PCT) has been reported as a potential biomarker to predict the severity of acute cholangitis (AC) or the need for urgent biliary decompression. This study aimed to identify and summarize the existing research about serum PCT and the severity of AC, and to find gaps towards which future studies can be targeted. Following the PRISMA extension for scoping reviews, MEDLINE, EMBASE, and Google Scholar were searched for all peer-reviewed articles with relevant keywords including “cholangitis” and “procalcitonin” from their inception to 13 July 2021. We identified six studies. All the studies employed a case-control design and aimed to evaluate the usefulness of serum PCT to predict the severity of AC with key identified outcomes. While the potential cut-off values of serum PCT for severe AC ranged from 1.8–3.1 ng/mL, studies used different severity criteria and the definition of urgent biliary decompression. No studies proposed cut-off PCT values for the need for urgent biliary decompression. This scoping review identified the current level of evidence regarding the usefulness of serum PCT in assessing the severity of AC. Further clinical research is warranted with a focus on standardized outcome measures employing prospective or experimental designs.
The Association between the Oral-Gut Axis and the Outcomes of Severe COVID-19 Patients Receiving Extracorporeal Membrane Oxygenation: A Case-Control Study
Authors: Yoshino Aya , Nakamura Yoshihiko , Hashiguchi Shiho , Ishida Shintaro , Mano Ryosuke , Nakamura Shinsuke , Kita Ryosuke , Seto Mika , Takata Tohru , Ishikura Hiroyasu , Kondo Seiji
Published: February 2022

The novel conceptual disease model, the oral–gut axis, which represents the immunomodulatory mutual relationship between oral and gut microbial compartments, has been attracting attention in relation to systemic health issues. We investigated whether this unique crosstalk influences the systemic condition of patients with COVID-19 infections who received extracorporeal membrane oxygenation (ECMO) in the intensive care unit (ICU) during April and December 2020. In this case-control study, patients were divided into two groups according to their survival (total entry size, n = 21; survivors, n = 13; non-survivors, n = 8). Patients were evaluated using the oral assessment guide from Fukuoka University (OAG-F) and the Bristol Stool Form Scale (BSFS) to examine the oral and fecal conditions. A blood-based inflammatory factor, the neutrophil-to-lymphocyte ratio (NLR), was used as an indicator of systemic immunity. The high total OAG-F scores were associated with both elevated BSFS and NLR values, and a mutually positive correlation between BSFS and NLR was observed. This indicated an interplay between oral deterioration, gut dysbiosis, and the impairment of immunity. Furthermore, oral deterioration was more frequently observed in non-survivors on day 14 of ICU admission. In addition, on days 7 and 21 of ICU admission, impaired immunity, reflected by an elevated NLR, was observed in non-survivors. However, the distribution of the gut microbiome—reflected by increased BSFS values—with the time it was examined was not directly observed in non-survivors. Taken together, these findings suggested that oral–gut health may be specifically associated with mortality in COVID-19 patients receiving ECMO in the ICU.
Establishing a Risk Assessment Framework for Marine Assets and Assessing Typhoon Lekima Storm Surge for the Laizhou Bay Coastal Area of the Bohai Sea, China
Authors: Li Jian , Mo Dongxue , Li Rui , Hou Yijun , Liu Qingrong
Published: February 2022

Effective risk assessment can reduce the economic losses and physical damage caused by marine dynamic processes, such as storm surges. Most risk assessments of marine disasters are based on regional parameters and discrete hazard grades. Targeted, multilevel, and multiangle risk assessments are urgently needed. This study focuses on specific types of affected infrastructure. We established a sensitivity matrix by considering the effects of different disaster causal factors on different types of affected infrastructure. Through this matrix, hazards, vulnerability, and emergency response and recovery capability were effectively combined in a risk assessment framework. We completed the risk calculation for multiple concurrent effects of disasters in areas with superimposed key infrastructure using complementary risk superposition. The hazard grade, vulnerability grade, and coefficient of emergency response and recovery capability were established based on the means of return period, characteristics of disaster distribution, types of affected infrastructure and disaster relief distance, and were continuous by solving functions, normal cumulative distributions, and analytic functions. On the basis of reasonable MIKE21 numerical simulation and abstract spatial distribution of vulnerable assets, we tested the rationality of the assessment system in the Lekima typhoon storm surge process. The results showed that the assessment system accurately reflected the risk of damage to the important infrastructure in terms of spatial distribution. Therefore, this risk assessment framework was suitable for the assessment of a marine dynamic disaster process in the lower Laizhou Bay coastal area of the Bohai Sea, China. Moreover, it provided a reference for disaster prevention and reduction, guided the way for decision making, and effectively reduced disaster losses.
Growth Heterogeneity of Chub Mackerel (Scomber japonicus) in the Northwest Pacific Ocean
Authors: Cai Kai , Kindong Richard , Ma Qiuyun , Han Xiaobin , Qin Song
Published: February 2022

Chub mackerel (Scomber japonicus) is a pelagic fish widely distributed in temperate and subtropical zones throughout the Indian and Pacific Oceans and is commercially exploited, particularly in the North Pacific. Although highly targeted in this region, little is known about their life history aspects. The objectives of this study are to evaluate the growth heterogeneities and ageing analysis of this species. We describe the length-at-age, weight-at-length, relative condition factor relationships, spatiotemporal heterogeneity and compare estimated growth parameter values to those reported from other regions. This study used data obtained from Chinese fishing vessels collected from 2016–2020 in the northwest Pacific Ocean. Length-weight data from 2686 specimens (40–294 mm, fork length; 0.8–311.8 g body weight) were analyzed, and the Length-weight relationship was W = (1.41 × 10−6) × FL3.37. Seven linear mixed-effects models (LMEM) were used to analyze the heterogeneity of length-weight relationships of Chub mackerel. The Length-weight relationships for Chub mackerel were best described by a model with random effects with both year and season (spring, summer, autumn) with the scalar parameter a. Age estimates were obtained from 175 specimens, and the length-at-estimated ages relationship was described using three non-linear candidate growth models. The von Bertalanffy growth model fit the data best for Chub mackerel in the northwest Pacific Ocean. Comparing the results to that of previous studies, we observed that individual Chub mackerel exhibited a slower growth rate than that observed in previous studies. In addition, relative condition factors varied among years, seasons, and regions. Information presented in this study provides an effective scientific basis for stock assessment and fishery management of Chub mackerel in the northwest Pacific Ocean.
Cerebral Protection in TAVR—Can We Do Without? A Real-World All-Comer Intention-to-Treat Study—Impact on Stroke Rate, Length of Hospital Stay, and Twelve-Month Mortality
Authors: Donà Carolina , Koschutnik Matthias , Nitsche Christian , Winter Max-Paul , Seidl Veronika , Siller-Matula Jolanta , Mach Markus , Andreas Martin , Bartko Philipp , Kammerlander Andreas Anselm , Goliasch Georg , Lang Irene , Hengstenberg Christian , Mascherbauer Julia
Published: February 2022

Background: Stroke associated with transcatheter aortic valve replacement (TAVR) is a potentially devastating complication. Until recently, the Sentinel™ Cerebral Protection System (CPS; Boston Scientific, Marlborough, MA, USA) has been the only commercially available device for mechanical prevention of TAVR-related stroke. However, its effectiveness is still undetermined. Objectives: To explore the impact of Sentinel™ on stroke rate, length of hospital stay (LOS), and twelve-month mortality in a single-center, real-world, all-comers TAVR cohort. Material and Methods: Between January 2019 and August 2020 consecutive patients were assigned to TAVR with or without Sentinel™ in a 1:1 fashion according to the treating operator. We defined as primary endpoint clinically detectable cerebrovascular events within 72 h after TAVR and as secondary endpoints LOS and 12-month mortality. Logistic and linear regression analyses were used to assess associations of Sentinel™ use with endpoints. Results: Of 411 patients (80 ± 7 y/o, 47.4% female, EuroSCORE II 6.3 ± 5.9%), Sentinel™ was used in 213 (51.8%), with both filters correctly deployed in 189 (46.0%). Twenty (4.9%) cerebrovascular events were recorded, ten (2.4%) of which were disabling strokes. Patients with Sentinel™ suffered 71% less (univariate analysis; OR 0.29, 95%CI 0.11–0.82; p = 0.02) and, respectively, 76% less (multivariate analysis; OR 0.24, 95%CI 0.08–0.76; p = 0.02) cerebrovascular events compared to patients without Sentinel™. Sentinel™ use was also significantly associated with shorter LOS (Regression coefficient −2.47, 95%CI −4.08, −0.87; p < 0.01) and lower 12-month all-cause mortality (OR 0.45; 95%CI 0.22–0.93; p = 0.03). Conclusion: In the present prospective all-comers TAVR cohort, patients with Sentinel™ use showed (1) lower rates of cerebrovascular events, (2) shortened LOS, and (3) improved 12-month survival. These data promote the use of a CPS when implanting TAVR valves.
Is There Any Witching in the Cryptocurrency Market?
Authors: Plastun Alex , Khomutenko Ludmila , Bashlai Serhii
Published: February 2022

This paper explores price effects caused by the expiration of derivatives in the cryptocurrency market. Applying different statistical tests (ANOVA, Mann–Whitney, and t-tests) and econometric methods (the modified cumulative abnormal return approach, regression analysis with dummy variables, and the trading simulation approach) to daily and weekly Bitcoin data over the period 2018–2021, the following hypotheses are tested: (H1) Expiration days create patterns in price behavior in the cryptocurrency market; and (H2) Price patterns can be exploited to generate abnormal profits from trading. The results suggest that expiration effects are only nominally present in the cryptocurrency market. There are differences in returns between expiration-related periods and average returns, but these differences are statistically insignificant. The only case in which an anomaly was detected was related to abnormally high returns during the week of expiration: returns during such weeks were positive in 65% of cases, and were on average 5 times higher than during usual weeks. Trading strategies based on this fact were able to generate results different from those of random trading, with a Sharpe ratio above 1. This is evidence in favor of the existence of a real price anomaly, which contradicts the efficient market hypothesis, and this could be implemented in the practice of traders and investors by creating trading strategies based on detected price effects or special technical analysis indicators to generate trading signals. For academics, these results might provide an opportunity to improve time series forecasting analysis in the case of Bitcoin.
Fires on Ice: Emerging Permafrost Peatlands Fire Regimes in Russia’s Subarctic Taiga
Authors: Kuklina Vera , Sizov Oleg , Rasputina Elena , Bilichenko Irina , Krasnoshtanova Natalia , Bogdanov Viktor , Petrov Andrey N.
Published: February 2022

Wildfires in permafrost areas, including smoldering fires (e.g., “zombie fires”), have increasingly become a concern in the Arctic and subarctic. Their detection is difficult and requires ground truthing. Local and Indigenous knowledge are becoming useful sources of information that could guide future research and wildfire management. This paper focuses on permafrost peatland fires in the Siberian subarctic taiga linked to local communities and their infrastructure. It presents the results of field studies in Evenki and old-settler communities of Tokma and Khanda in the Irkutsk region of Russia in conjunction with concurrent remote sensing data analysis. The study areas located in the discontinuous permafrost zone allow examination of the dynamics of wildfires in permafrost peatlands and adjacent forested areas. Interviews revealed an unusual prevalence and witness-observed characteristics of smoldering peatland fires over permafrost, such as longer than expected fire risk periods, impacts on community infrastructure, changes in migration of wild animals, and an increasing number of smoldering wildfires including overwintering “zombie fires” in the last five years. The analysis of concurrent satellite remote sensing data confirmed observations from communities, but demonstrated a limited capacity of satellite imagery to accurately capture changing wildfire activity in permafrost peatlands, which may have significant implications for global climate.
The Case for Clinical Trials with Novel GABAergic Drugs in Diabetes Mellitus and Obesity
Authors: Antoni Ferenc A.
Published: February 2022

Obesity and diabetes mellitus have become the surprising menaces of relative economic well-being worldwide. Gamma amino butyric acid (GABA) has a prominent role in the control of blood glucose, energy homeostasis as well as food intake at several levels of regulation. The effects of GABA in the body are exerted through ionotropic GABAA and metabotropic GABAB receptors. This treatise will focus on the pharmacologic targeting of GABAA receptors to reap beneficial therapeutic effects in diabetes mellitus and obesity. A new crop of drugs selectively targeting GABAA receptors has been under investigation for efficacy in stroke recovery and cognitive deficits associated with schizophrenia. Although these trials have produced mixed outcomes the compounds are safe to use in humans. Preclinical evidence is summarized here to support the rationale of testing some of these compounds in diabetic patients receiving insulin in order to achieve better control of blood glucose levels and to combat the decline of cognitive performance. Potential therapeutic benefits could be achieved (i) By resetting the hypoglycemic counter-regulatory response; (ii) Through trophic actions on pancreatic islets, (iii) By the mobilization of antioxidant defence mechanisms in the brain. Furthermore, preclinical proof-of-concept work, as well as clinical trials that apply the novel GABAA compounds in eating disorders, e.g., olanzapine-induced weight-gain, also appear warranted.
An Immunological Perspective of Circulating Tumor Cells as Diagnostic Biomarkers and Therapeutic Targets
Authors: Dotse Eunice , Lim King H. , Wang Meijun , Wijanarko Kevin Julio , Chow Kwan T.
Published: February 2022

Immune modulation is a hallmark of cancer. Cancer–immune interaction shapes the course of disease progression at every step of tumorigenesis, including metastasis, of which circulating tumor cells (CTCs) are regarded as an indicator. These CTCs are a heterogeneous population of tumor cells that have disseminated from the tumor into circulation. They have been increasingly studied in recent years due to their importance in diagnosis, prognosis, and monitoring of treatment response. Ample evidence demonstrates that CTCs interact with immune cells in circulation, where they must evade immune surveillance or modulate immune response. The interaction between CTCs and the immune system is emerging as a critical point by which CTCs facilitate metastatic progression. Understanding the complex crosstalk between the two may provide a basis for devising new diagnostic and treatment strategies. In this review, we will discuss the current understanding of CTCs and the complex immune-CTC interactions. We also present novel options in clinical interventions, targeting the immune-CTC interfaces, and provide some suggestions on future research directions.
The Shortcomings of COVID-19 Testing in Ecuador: Time to Incentivize Research and Innovation
Authors: Chalen Izan , Cobo María Mercedes , Gutierrez Bernardo , Carrazco-Montalvo Andrés , Ponce Patricio , Cisneros-Heredia Diego F.
Published: February 2022

The COVID-19 pandemic hit Ecuador severely. The country caught the attention of international media due to its high death toll and overwhelmed healthcare system. The clinical diagnostics system was rapidly overloaded, and the import of PCR tests was delayed. The case of Ecuador illustrates how middle-income countries rely heavily on the importation of biotechnological products for their healthcare systems. The Ecuadorian experience during the COVID-19 pandemic serves as a call for the formation of policies for the development of the biotechnological industry.
Identification of Potential Genes Encoding Protein Transporters in Arabidopsis thaliana Glucosinolate (GSL) Metabolism
Authors: Harun Sarahani , Afiqah-Aleng Nor , Abdul Hadi Fatin Izzati , Lam Su Datt , Mohamed-Hussein Zeti-Azura
Published: February 2022

Several species in Brassicaceae produce glucosinolates (GSLs) to protect themselves against pests. As demonstrated in A. thaliana, the reallocation of defence compounds, of which GSLs are a major part, is highly dependent on transport processes and serves to protect high-value tissues such as reproductive tissues. This study aimed to identify potential GSL-transporter proteins (TPs) using a network-biology approach. The known A. thaliana GSL genes were retrieved from the literature and pathway databases and searched against several co-expression databases to generate a gene network consisting of 1267 nodes and 14,308 edges. In addition, 1151 co-expressed genes were annotated, integrated, and visualised using relevant bioinformatic tools. Based on three criteria, 21 potential GSL genes encoding TPs were selected. The AST68 and ABCG40 potential GSL TPs were chosen for further investigation because their subcellular localisation is similar to that of known GSL TPs (SULTR1;1 and SULTR1;2) and ABCG36, respectively. However, AST68 was selected for a molecular-docking analysis using AutoDOCK Vina and AutoDOCK 4.2 with the generated 3D model, showing that both domains were well superimposed on the homologs. Both molecular-docking tools calculated good binding-energy values between the sulphate ion and Ser419 and Val172, with the formation of hydrogen bonds and van der Waals interactions, respectively, suggesting that AST68 was one of the sulphate transporters involved in GSL biosynthesis. This finding illustrates the ability to use computational analysis on gene co-expression data to screen and characterise plant TPs on a large scale to comprehensively elucidate GSL metabolism in A. thaliana. Most importantly, newly identified potential GSL transporters can serve as molecular tools in improving the nutritional value of crops.
Modelling of Lubricated Electrical Contacts
Authors: Jackson Robert L. , Angadi Santosh
Published: February 2022

Electrical contacts, although critically important for a wide range of applications, are susceptible to degradation due to fretting corrosion, especially when sliding and vibrations occur. To overcome fretting corrosion and sliding wear, lubricants are often used. However, the use of lubricants can cause other detrimental issues. Lubricants usually consist of non-conductive fluids such as hydrocarbons and fluorocarbons. Due to fluid dynamics, when sliding, vibration or other excitation occurs, these fluids can cause prolonged gaps between the conducting metal surfaces. Practically, this has been observed in data centers where vibrations due to technician maintenance or even earthquakes can occur. Depending on the viscosity and roughness of the surfaces, the time it takes these connector surfaces to return to solid conductive contact can be many seconds or longer. This work uses a novel theoretical model of the coupled fluid and solid mechanics between the rough metallic surfaces to evaluate these intermittent breaks in contact due to sliding. The influence of variation in lubricant properties, roughness, contact radius and contact force are considered by the model.
Synthesis of Novel Pyrazolo[3,4-b]pyridines with Affinity for β-Amyloid Plaques
Authors: Vidali Veroniki P. , Nigianni Georgia , Athanassopoulou Georgia D. , Canko Aleksander , Mavroidi Barbara , Matiadis Dimitris , Pelecanou Maria , Sagnou Marina
Published: February 2022

Three novel pyrazolo[3,4-b]pyridines were synthesized via the cyclization of 5-amino-1-phenylpyrazole with the corresponding unsaturated ketone in the catalytic presence of ZrCl4. The ketones were afforded by modifying a stabilized ylide facilitated Wittig reaction in fairly high yields. The novel compounds exhibited exciting photophysical properties with the dimethylamine phenyl-bearing pyrazolopyridine showing exceptionally large Stoke’s shifts. Finally, both the dimethylamino- and the pyrene-substituted compounds demonstrated high and selective binding to amyloid plaques of Alzheimer’s disease (AD) patient brain slices upon fluorescent confocal microscopy observation. These results reveal the potential application of pyrazolo[3,4-b]pyridines in the development of AD amyloid plaque probes of various modalities for AD diagnosis.
Investigation of the Effect of Graphene Oxide on the Properties and Microstructure of Clay-Cement Composite Grouting Materials
Authors: Ling Xianzhang , Guo Xiaoyu , Zhong Jing , Ma Jinji , Tang Liang , Xing Dongliang , Su Jianguang , Cong Shengyi
Published: February 2022

Reductions in bleeding rates and bulk shrinkage of grouting repair materials comprise the key to solving the leakage of earth–rock dams. In this paper, an anti-seepage grouting material for earth–rock dam was developed by introducing mineral admixtures and graphene oxide (GO) nano sheets into low-cost clay–cement grouting materials and by adding polycarboxylate superplasticizers (PCs) to improve slurry viscosity. The experimental results show that the shear stress and viscosity of the slurry increase with the increase in GO concentration, and the slurry has a certain thixotropy. GO can provide a platform to promote the formation of hydration products and fill the pores of clay particles due to its high specific surface area and low volume; in this paper, the microstructure of clay–cement–graphene oxide (CCGO) grouting materials were improved. Therefore, the bleeding rate, bulk shrinkage rate, setting time and unconfined compressive strength (UCS) of the sample were macroscopically improved. In particular, the bleeding rate and bulk shrinkage rate were shown to be 0% when the content of GO reached 1.08 g/kg. Thus, the grouting anti-seepage and reinforcement performance of CCGO grouting materials were improved.
Stress Calculations of Heat Storage Tanks
Authors: Wiśniewska Weronika , Matysko Robert
Published: February 2022

Stress calculations are necessary to determine the feasibility and profitability of a heat storage tank’s construction. The article presented normative methods of stress calculations for a heat storage tank. Results were verified by finite element analysis. These stress calculations enabled us to determine wall and weld thickness. The calculations were made on the example of a tank with a nominal pressure of 10 bar. The work undertook an extensive analysis of the stresses occurring in a pressure tank, described the finite element method and showed examples of ways in which it could be used. During stress analysis, three types of materials were compared: carbon steel St0 (S185), stainless steel (304) and boiler steel (P 265 GH). A brief overview of types of thermal energy storages was also provided.
Mild Solutions of Second-Order Semilinear Impulsive Differential Inclusions in Banach Spaces
Authors: Pavlačková Martina , Taddei Valentina
Published: February 2022

In this paper, the existence of a mild solution to the Cauchy problem for impulsive semilinear second-order differential inclusion in a Banach space is investigated in the case when the nonlinear term also depends on the first derivative. This purpose is achieved by combining the Kakutani fixed point theorem with the approximation solvability method and the weak topology. This combination enables obtaining the result under easily verifiable and not restrictive conditions on the impulsive terms, the cosine family generated by the linear operator and the right-hand side while avoiding any requirement for compactness. Firstly, the problems without impulses are investigated, and then their solutions are glued together to construct the solution to the impulsive problem step by step. The paper concludes with an application of the obtained results to the generalized telegraph equation with a Balakrishnan–Taylor-type damping term.
On a Modified Weighted Exponential Distribution with Applications
Authors: Chesneau Christophe , Kumar Vijay , Khetan Mukti , Arshad Mohd
Published: February 2022

Practitioners in all applied domains value simple and adaptable lifetime distributions. They make it possible to create statistical models that are relatively easy to manage. A novel simple lifetime distribution with two parameters is proposed in this article. It is based on a parametric mixture of the exponential and weighted exponential distributions, with a mixture weight depending on a parameter of the involved distribution; no extra parameter is added in this mixture operation. It can also be viewed as a special generalized mixture of two exponential distributions. This decision is based on sound mathematical and physical reasoning; the weight modification allows us to combine some joint properties of the exponential and weighted exponential distribution, which are known as complementary in several modeling aspects. As a result, the proposed distribution may have a decreasing or unimodal probability density function and possess the demanded increasing hazard rate property. Other properties are studied, such as the moments, Bonferroni and Lorenz curves, Rényi entropy, stress-strength reliability, and mean residual life function. Subsequently, a part is devoted to the associated model, which demonstrates how it can be used in a real-world statistical scenario involving data. In this regard, we demonstrate how the estimated model performs well using five different estimation methods and simulated data. The analysis of two data sets demonstrates these excellent results. The new model is compared to the weighted exponential, Weibull, gamma, and generalized exponential models for performance. The obtained comparison results are overwhelmingly in favor of the proposed model according to some standard criteria.
Synthesis of Marine Cyclopeptide Galaxamide Analogues as Potential Anticancer Agents
Authors: Li Daichun , Liao Xiaojian , Zhong Shenghui , Zhao Bingxin , Xu Shihai
Published: February 2022

In this paper, eight new galaxamide analogues (Z-1~Z-8) were synthesized and evaluated for their cytotoxic activities against five cancer cell lines, MCF-7, MD-MBA-231, HepG2, Hela, and A549, using MTT assays. The modified analogue Z-6 displayed broad spectrum cytotoxic activity toward each tested cell line with IC50 values of 1.65 ± 0.30 (MCF-7), 2.91 ± 0.17 (HepG2), 4.59 ± 0.27 (MD-MBA-231), 5.69 ± 0.37 (Hela), and 5.96 ± 0.41 (A549) μg/mL, respectively. The galaxamides Z-3 and Z-6 induced concentration-dependent apoptosis of the MCF-7 cells after 72 h as evaluated by the flow cytometry experiment. The results showed that these compounds could induce MCF-7 cell apoptosis by arresting the G0/G1 phase of the cell cycle and finally achieving the effect of inhibiting the proliferation of MCF-7 cells.
Prematurity—Risk Factor or Coincidence in Congenital Glaucoma?
Authors: Dragosloveanu Christiana D. M. , Potop Vasile , Coviltir Valeria , Dinu Valentin , Păsărică Mihai , Ducan Irina L. , Maier Călina , Dragosloveanu Şerban
Published: February 2022

Background and Objective: To correlate the intraocular pressure with the postconceptional age and identify a statistically significant connection between congenital glaucoma and prematurity. Materials and Methods: The current paper is a retrospective, comparative, case-control study. Data collection featured maternal age, gestational age at birth, birth weight, and intraocular ocular pressure (IOP) measurements. Results: Forty-two eyes of 21 children underwent examination. The participants were assigned into two groups. The Preterm-Glaucoma (PG) group included eight preterm-born children diagnosed with glaucoma, whereas the Preterm (P) group was comprised of premature newborns without the aforementioned condition. There was no statistically relevant difference in birth weight (p = 0.691078) nor in mean gestational age (p = 0.752623) between the two groups. The mean IOP in the PG group was 23.813 ± 4.5493, whereas in the P group, it ranged around 13.231 ± 1.0699, p < 0.0001. Using mixed-effects models, we obtained a reduction in IOP of 0.45 mmHg per week in the first month of life. A further weekly reduction of 0.36 mmHg was achieved in the next two months. Conclusions: The mean IOP of prematurely born children decreased with age. Our findings correlate with previously conducted studies, however, the drop in IOP values exceeded any data published so far. We found no correlation between prematurity and the incidence of congenital glaucoma.