bluuebunny/crossref_metadata_2025 huggingface dataset:
Clin.iobio: A Collaborative Diagnostic Workflow to Enable Team-Based Precision Genomics
Authors: Ward Alistair , Velinder Matt , Di Sera Tonya , Ekawade Aditya , Malone Jenkins Sabrina , Moore Barry , Mao Rong , Bayrak-Toydemir Pinar , Marth Gabor
Published: January 2022

The primary goal of precision genomics is the identification of causative genetic variants in targeted or whole-genome sequencing data. The ultimate clinical hope is that these findings lead to an efficacious change in treatment for the patient. In current clinical practice, these findings are typically returned by expert analysts as static, text-based reports. Ideally, these reports summarize the quality of the data obtained, integrate known gene–phenotype associations, follow allele segregation and affected status within the sequenced samples, and weigh computational evidence of pathogenicity. These findings are used to prioritize the variant(s) most likely to cause the given patient’s phenotypes. In most diagnostic settings, a team of experts contribute to these reports, including bioinformaticians, clinicians, and genetic counselors, among others. However, these experts often do not have the necessary tools to review genomic findings, test genetic hypotheses, or query specific gene and variant information. Additionally, team members often rely on different tools and methods based on their given expertise, resulting in further difficulties in communicating and discussing genomic findings. Here, we present clin.iobio—a web-based solution to collaborative genomic analysis that enables diagnostic team members to focus on their area of expertise within the diagnostic process, while allowing them to easily review and contribute to all steps of the diagnostic process. Clin.iobio integrates tools from the popular iobio genomic visualization suite into a comprehensive diagnostic workflow, encompassing (1) genomic data quality review, (2) dynamic phenotype-driven gene prioritization, (3) variant prioritization using a comprehensive set of knowledge bases and annotations, (4) and an exportable findings summary. In conclusion, clin.iobio is a comprehensive solution to team-based precision genomics, the findings of which stand to inform genomic considerations in clinical practice.
Integration of Genomic Risk Scores to Improve the Prediction of Childhood Asthma Diagnosis
Authors: Kothalawala Dilini M. , Kadalayil Latha , Curtin John A. , Murray Clare S. , Simpson Angela , Custovic Adnan , Tapper William J. , Arshad S. Hasan , Rezwan Faisal I. , Holloway John W. ,   on behalf of STELAR/UNICORN investigators
Published: January 2022

Genome-wide and epigenome-wide association studies have identified genetic variants and differentially methylated nucleotides associated with childhood asthma. Incorporation of such genomic data may improve performance of childhood asthma prediction models which use phenotypic and environmental data. Using genome-wide genotype and methylation data at birth from the Isle of Wight Birth Cohort (n = 1456), a polygenic risk score (PRS), and newborn (nMRS) and childhood (cMRS) methylation risk scores, were developed to predict childhood asthma diagnosis. Each risk score was integrated with two previously published childhood asthma prediction models (CAPE and CAPP) and were validated in the Manchester Asthma and Allergy Study. Individually, the genomic risk scores demonstrated modest-to-moderate discriminative performance (area under the receiver operating characteristic curve, AUC: PRS = 0.64, nMRS = 0.55, cMRS = 0.54), and their integration only marginally improved the performance of the CAPE (AUC: 0.75 vs. 0.71) and CAPP models (AUC: 0.84 vs. 0.82). The limited predictive performance of each genomic risk score individually and their inability to substantially improve upon the performance of the CAPE and CAPP models suggests that genetic and epigenetic predictors of the broad phenotype of asthma are unlikely to have clinical utility. Hence, further studies predicting specific asthma endotypes are warranted.
Changes in Bihemispheric Structural Connectivity Following Middle Cerebral Artery Infarction
Authors: Kim Dae Hyun , Kang Hyunkoo
Published: January 2022

This study investigated the changes in the structural connectivity of the bilateral hemispheres over time following a middle cerebral artery infarction. Eighteen patients in the subacute group and nine patients in the chronic group with mild upper extremity motor impairment (Fugl-Meyer motor assessment score for the upper limb > 43) following middle cerebral artery infarction were retrospectively evaluated in this study. All the patients underwent T1-weighted and diffusion tensor imaging. Tract-based statistical analyses of fractional anisotropy were used to compare the changes in the bilateral structural connectivity with those of age-matched normal controls. The corticospinal tract pathway of the affected hemisphere, corpus callosum, and corona radiata of the unaffected hemisphere had decreased structural connectivity in the subacute group, while the motor association area and anterior corpus callosum in the bilateral frontal lobes had increased structural connectivity in the chronic group. The bilateral hemispheres were influenced even in patients with mild motor impairment following middle cerebral artery infarction, and the structural connectivity of the bilateral hemispheres changed according to the time following the stroke.
Risk Factors for Pancreatic Cancer: Emerging Role of Viral Hepatitis
Authors: Gheorghe Gina , Diaconu Camelia Cristina , Ionescu Vlad , Constantinescu Gabriel , Bacalbasa Nicolae , Bungau Simona , Gaman Mihnea-Alexandru , Stan-Ilie Madalina
Published: January 2022

Pancreatic cancer is one of the most aggressive malignant neoplastic diseases. The incidence and mortality rates of this disease vary depending on geographical area, which might be explained by the different exposure to risk factors. To improve the prognosis of patients with pancreatic cancer, different approaches are needed for an earlier diagnosis. Identification of risk factors and implementation of screening strategies are essential for a better prognosis. Currently, the risk factors for pancreatic cancer fall into two broad categories, namely extrinsic and intrinsic factors. Extrinsic factors include alcohol consumption, smoking, a diet rich in saturated fats, and viral infections such as chronic infection with hepatitis B and C viruses. The pathophysiological mechanisms explaining how these hepatotropic viruses contribute to the development of pancreatic cancer are not fully elucidated. The common origin of hepatocytes and pancreatic cells in the multipotent endodermal cells, the common origin of the blood vessels and biliary ducts of the pancreas and the liver, or chronic inflammatory changes may be involved in this interaction. A careful monitoring of patients with viral liver infections may contribute to the early diagnosis of pancreatic cancer and improve the prognosis of these patients.
Blockchain-Based Security Model for LoRaWAN Firmware Updates
Authors: Mtetwa Njabulo Sakhile , Tarwireyi Paul , Sibeko Cecilia Nombuso , Abu-Mahfouz Adnan , Adigun Matthew
Published: January 2022

The Internet of Things (IoT) is changing the way consumers, businesses, and governments interact with the physical and cyber worlds. More often than not, IoT devices are designed for specific functional requirements or use cases without paying too much attention to security. Consequently, attackers usually compromise IoT devices with lax security to retrieve sensitive information such as encryption keys, user passwords, and sensitive URLs. Moreover, expanding IoT use cases and the exponential growth in connected smart devices significantly widen the attack surface. Despite efforts to deal with security problems, the security of IoT devices and the privacy of the data they collect and process are still areas of concern in research. Whenever vulnerabilities are discovered, device manufacturers are expected to release patches or new firmware to fix the vulnerabilities. There is a need to prioritize firmware attacks, because they enable the most high-impact threats that go beyond what is possible with traditional attacks. In IoT, delivering and deploying new firmware securely to affected devices remains a challenge. This study aims to develop a security model that employs Blockchain and the InterPlanentary File System (IPFS) to secure firmware transmission over a low data rate, constrained Long-Range Wide Area Network (LoRaWAN). The proposed security model ensures integrity, confidentiality, availability, and authentication and focuses on resource-constrained low-powered devices. To demonstrate the utility and applicability of the proposed model, a proof of concept was implemented and evaluated using low-powered devices. The experimental results show that the proposed model is feasible for constrained and low-powered LoRaWAN devices.
Residents’ Perceptions of Sustainable Tourism Destination Recovery: The Case of Northern Cyprus
Authors: Seyedabolghasemi Maryam Alsadat , Kilic Hasan , Avci Turgay , Eluwole Kayode Kolawole , Lasisi Taiwo Temitope
Published: January 2022

As nations and tourism destinations are beginning to relax nonpharmaceutical measures for the prevention of the COVID-19 virus, a major quest of tourism stakeholders is to restart and restore the once viable and productive industry to its prior state. While the urge to restart and restore may necessitate a strategic plan and drastic measures, care must be taken not to undermine the sustainability of the destination. The current study seeks to understand the perceptions of residents of Northern Cyprus as key tourism stakeholders concerning the impacts of COVID-19 to the island’s tourism activities and recommendations for recovery post pandemic. To this end, the study used grounded theory and semistructured interviews to explore how residents perceive the contribution of focused advertisements and stakeholder engagement in the sustainable restoration of tourism activities post COVID-19 on the island. While divergent opinions were gathered, it can be inferred that stakeholders expect the implementation of strategic plans aided by focused advertisements to ensure the sustainability of their tourist destinations. Policy directions and academic contributions are also stated as requirements.
Topology, Vegetation and Stratigraphy of Far Eastern Aapa Mires (Khabarovsk Region, Russia)
Authors: Kutenkov Stanislav , Chakov Vladimir , Kuptsova Viktoriya
Published: January 2022

Aapa mires (string-flark fens) are one of the main types of mires in northern Eurasia. It has an almost continuous distribution from Scandinavia to Kamchatka, disappearing in continental climate areas and becoming one of the dominant types in more oceanic zones. This article first presents the topological features of string-flark aapa, their vegetation and peat stratigraphy related to different elements of microrelief at the southernmost borders of boreal mires of cryolithozone (51–52 N), in the Lower Amur region (Russia). String-flark fens are very similar to the aapa mires originally reported for the European North. The waterlogged minerotrophic central fen, with a ribbed surface pattern, is surrounded by oligotrophic bogs. The mosaic structure of the vegetation cover in the fens is determined by microtopography: mesooligotrophic dwarf shrub–herb–sphagnum strings, mesoeutrophic herb–sphagnum lawns, and sparse herb cover in water flarks. The flora, for the most part, corresponds with the European aapa, and has some characteristics of eastern features. We relate the localized evolution of string-flark complexes with water basin hydrology changes. The formation of string-flark complexes in pre-existing fens was preceded by the cessation of river flood waters over the surface of the mires. The further decline of erosion has led to the development of dwarf shrub–sphagnum communities containing microrelief. The immature strings of the aapa mires attest to the ongoing active change processes of the mires.
How Might World Heritage Status Support the Protection of Sacred Natural Sites? An Analysis of Nomination Files, Management, and Governance Contexts
Authors: Verschuuren Bas , Ormsby Alison , Jackson Wendy
Published: January 2022

This study provides an overview of how sacred natural sites are given recognition within the World Heritage system. It offers an analysis of the extent to which sacred natural sites that are part of nine World Heritage sites are recognised in site nomination files, management plans, and governance of these sites. The World Heritage sites are located across all continents except for Antarctica. We analysed sites in Australia, Greece, Guatemala, India, Japan, Kenya, Malaysia, New Zealand and the Russian Federation. We found that the cultural and spiritual significance of sacred natural sites is under-recognised, especially in natural World Heritage sites. In addition, Indigenous and religious custodians are frequently excluded from site management and governance. We make four recommendations for improving the recognition of sacred natural sites and the involvement of their custodians in the World Heritage process and in site nomination, governance, and management: (1) identification and recognition of sacred natural sites including their associated cultural and spiritual values; (2) recognition of, and articulated roles for custodians of sacred natural sites in the governance and management of World Heritage sites; (3) increased uptake of religious groups and Indigenous Peoples’ conservation approaches to the joint management of World Heritage sites that contain sacred natural sites, and (4) prevention of exclusion of custodians and ecological migration by applying inclusive conservation practices through rights-based approaches.
Spatial Patterns and Driving Factors of Rural Population Loss under Urban–Rural Integration Development: A Micro-Scale Study on the Village Level in a Hilly Region
Authors: Liu Yaqiu , Zhang Xiaoqian , Xu Meng , Zhang Xinghao , Shan Bowen , Wang Ailing
Published: January 2022

Under the background of urban–rural integration, balanced development between urban and rural areas has been increasingly advocated. Rural population loss (RPL) is not only due to the laws of social and economic development but also the comprehensive action of natural, social, and economic factors. Taking 774 administrative villages in Laiyang County, which is in a hilly region, as our research area, we comprehensively used spatial analysis and geographic detectors to explore the spatial characteristics and driving factors of RPL, which was significantly correlated with rural planning. The research demonstrated that: (1) The rural population in Laiyang County generally had a low level of RPL (1.9%), but each village varied greatly. The village with the greatest RPL had a rate of 56%. The RPL between urban and rural areas, towns and streets, and villages and villages were unbalanced, and rural population flow mainly occurred between urban and rural areas. (2) RPL in Laiyang County was generally low in the central urban area and high in the northern and southern areas. Population loss presents agglomeration globally and high–low agglomeration locally. (3) The distance from village to county, elevation, cultivated land quantity, collective economic income, village area, and ecological service value were the key factors influencing RPL in Laiyang County. When comparing the dominant factors, the interaction between collective income and elevation was the strongest. Exploring the spatial characteristics and influencing factors of RPL provided us with ideas for the classified promotion of rural revitalization, preparation of rural development planning, and promotion of the integrated development of urban and rural areas.
Documentary Evidence of 17th Century Landcover and Climate Change in Northern China and Mongolia Compared to Modern Spectral Greening Trends
Authors: Kempf Michael
Published: January 2022

Fighting land degradation of semi-arid and climate-sensitive grasslands are among the most urgent tasks of current eco-political agenda. Particularly, northern China and Mongolia are prone to climate-induced surface transformations, which were reinforced by the heavily increased numbers of livestock during the 20th century. Extensive overgrazing and resource exploitation amplified regional climate change effects and triggered intensified land degradation that forced policy-driven interventions to prevent desertification. In the past, however, the regions have been subject to continuous shifts in environmental and socio-cultural and political conditions, which makes it particularly difficult to distinguish into regional anthropogenic impact and global climate change effects. This article presents analyses of historical written sources, palaeoenvironmental data, and Normalized Difference Vegetation Index (NDVI) temporal series from the Moderate Resolution Imaging Spectroradiometer (MODIS) to compare landcover change during the Little Ice Age (LIA) and current spectral greening trends over the period 2001–2020. Results show that decreasing precipitation and temperature records triggered increased land degradation during the late 17th century in the transition zone from northern China and Inner Mongolia Autonomous Region to Mongolia. From current climate change perspectives, modern vegetation shows enhanced physical vegetation response related to an increase in precipitation (Ptotal) and temperature (T). Vegetation response is strongly related to Ptotal and T and an increase in physical plant condition indicates local to regional grassland recovery compared to the past 20-year average.
Preliminary Model-Based Evaluation of Water Conservation Strategies in a Semi-Arid Urban Zone
Authors: Zúñiga-Estrada Marcelino Antonio , Lizárraga-Mendiola Liliana , Bigurra-Alzati Carlos Alfredo , Aldana-Alonso Sergio Esteban , Ramírez-Núñez Jorge Santiago , Vázquez-Rodríguez Gabriela A.
Published: January 2022

The U.S. Environmental Protection Agency stormwater management model was applied to a semi-arid urban micro watershed. The sub-catchment’s current features were modeled as scenario A, while the insertion of a set of LID technologies (rain barrels, bioretention cells, permeable pavement, and infiltration trenches) was represented as scenario B. A third scenario (C), considering only the most feasible LID technologies, was also modeled. All the scenarios were evaluated under two representative storm events (30 and 9 mm in two consecutive days, and 39 mm of rainfall in one day) occurred during the sampling performed in this study. Water quality was also simulated for a 30-mm storm event and compared against field assessment results after a real 30-mm storm event. Through the model, the inefficiency of current evacuation methods after 30- and 39-mm storm events was demonstrated. Simulation of scenario B showed that LID technologies could satisfactorily diminish peak flows generated by the selected storm events as well as runoff-conveyed pollution, while the realistic scenario allowed a lower but satisfactory hydrological performance and almost the same runoff quality than scenario B. This preliminary study could contribute to spread awareness about the benefits of LID technologies in semi-arid urban areas of the developing world.
FGFR Pathway Inhibition in Gastric Cancer: The Golden Era of an Old Target?
Authors: Lengyel Csongor G. , Hussain Sadaqat , Seeber Andreas , Jamil Nidhamalddin Sara , Trapani Dario , Habeeb Baker S. , Elfaham Essam , Mazher Syed Ayub , Seid Fahmi , Khan Shah Z. , El Bairi Khalid , Odhiambo Andrew , Altuna Sara C. , Petrillo Angelica
Published: January 2022

Gastric cancer (GC) is the third leading cause of cancer-associated death worldwide. The majority of patients are diagnosed at an advanced/metastatic stage of disease due to a lack of specific symptoms and lack of screening programs, especially in Western countries. Thus, despite the improvement in GC therapeutic opportunities, the survival is disappointing, and the definition of the optimal treatment is still an unmet need. Novel diagnostic techniques were developed in clinical trials in order to characterize the genetic profile of GCs and new potential molecular pathways, such as the Fibroblast Growth Factor Receptor (FGFR) pathway, were identified in order to improve patient’s survival by using target therapies. The aim of this review is to summarize the role and the impact of FGFR signaling in GC and to provide an overview regarding the potential effectiveness of anti-FGFR agents in GC treatment in the context of precision medicine.
Deep Sea Water-Dissolved Organic Matter Intake Improves Hyperlipidemia and Inhibits Thrombus Formation and Vascular Inflammation in High-Fat Diet Hamsters
Authors: Wu Chia-Chun , Cheng Yu-Hsuan , Chen Kuo-Hsin , Chien Chiang-Ting
Published: January 2022

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease caused by oxidative stress, inflammation and lipid deposition within liver cells, and is subsequently contributing to cardiovascular diseases such as atherosclerosis. Deep sea water (DSW) is characterized by its clearance and abundant nutrients with antioxidant and anti-inflammatory activity to confer therapeutic potential. We aimed to explore the therapeutic capability of our prepared multi-filtration DSW-dissolved organic matter (DSW-DOM) on high-fat diet-induced hyperlipidemia and endothelial dysfunction in hamsters. A high-fat/high-cholesterol diet led to increased oxidative stress, including blood reactive oxygen species (ROS), plasma malondialdehyde (MDA) and hepatic CYP2E1 expression; an increased hyperlipidemic profile and SREBP 1-mediated fatty liver; promoted NFκB p65-mediated hepatic inflammation; triggered PARP-mediated hepatic apoptosis; and enhanced endothelial intercellular adhesion molecule-1 (ICAM-1) and von Willebrand factor (VWF)-mediated atherosclerosis associated with the depressed hepatic antioxidant Paraoxonase 1 (PON1) expression. The DSW-DOM-enriched 1295 fraction, with strong H2O2 scavenging activity, efficiently reduced several oxidative stress parameters, the lipid profile, inflammation, and apoptosis, possibly through the PON1-mediated antioxidant capability. Furthermore, DSW-DOM treatment significantly decreased the endothelial ICAM-1 and VWF expression, subsequently leading to the elongation of time to occlusion of FeCl3-induced arterial thrombosis and to the inhibition of FeCl3-induced fluorescent platelet adhesion to mesentery arterioles in the high-fat diet. Based on the above results, our data suggest that DSW-DOM intake via antioxidant defense mechanisms confers protective effects against high-fat diet-enhanced, oxidative stress-mediated hyperlipidemia, and endothelial dysfunction evoked atherosclerosis by downregulating oxidative injury, lipogenesis, inflammation and apoptosis.
Identification of an Amylomaltase from the Halophilic Archaeon Haloquadratum walsbyi by Functional Metagenomics: Structural and Functional Insights
Authors: Leoni Claudia , Manzari Caterina , Tran Hai , Golyshin Peter N. , Pesole Graziano , Volpicella Mariateresa , Ceci Luigi R.
Published: January 2022

Amylomaltases are prokaryotic 4-α-glucanotransferases of the GH77 family. Thanks to the ability to modify starch, they constitute a group of enzymes of great interest for biotechnological applications. In this work we report the identification, by means of a functional metagenomics screening of the crystallization waters of the saltern of Margherita di Savoia (Italy), of an amylomaltase gene from the halophilic archaeon Haloquadratum walsbyi, and its expression in Escherichia coli cells. Sequence analysis indicated that the gene has specific insertions yet unknown in homologous genes in prokaryotes, and present only in amylomaltase genes identified in the genomes of other H. walsbyi strains. The gene is not part of any operon involved in the metabolism of maltooligosaccharides or glycogen, as it has been found in bacteria, making it impossible currently to assign a precise role to the encoded enzyme. Sequence analysis of the H. walsbyi amylomaltase and 3D modelling showed a common structure with homologous enzymes characterized in mesophilic and thermophilic bacteria. The recombinant H. walsbyi enzyme showed starch transglycosylation activity over a wide range of NaCl concentrations, with maltotriose as the best acceptor substrate compared to other maltooligosaccharides. This is the first study of an amylomaltase from a halophilic microorganism.
The Influence of an Acute Bout of Aerobic Exercise on Vascular Endothelial Function in Moderate Stages of Chronic Kidney Disease
Authors: Forsse Jeffrey S. , Papadakis Zacharias , Peterson Matthew N. , Taylor James Kyle , Hess Burritt W. , Schwedock Nicholas , Allison Dale C. , Griggs Jackson O. , Wilson Ronald L. , Grandjean Peter W.
Published: January 2022

Chronic kidney disease (CKD) is directly influenced by the deleterious effects of systemic inflammation and oxidative stress. The vascular endothelium may transiently respond to aerobic exercise and improve post-exercise vascular renal function in moderate stages of CKD. Brachial artery flow-mediated dilation (FMD) is a nitric-oxide-dependent measure of endothelial function that is transiently potentiated by exercise. The purpose of the study was to determine the acute influence of a single bout of high-intensity interval exercise (HIIE) or steady-state moderate-intensity exercise (SSE) on endothelial dysfunction in moderate stages of CKD. Twenty participants (n = 6 men; n = 14 women) completed 30 min of SSE (65%) and HIIE (90:20%) of VO2reserve in a randomized crossover design. FMD measurements and blood samples were obtained before, 1 h, and 24 h post-exercise. FMD responses were augmented 1 h post-exercise in both conditions (p < 0.005). Relative to pre-exercise measures, total antioxidant capacity increased by 4.3% 24 h post-exercise (p = 0.012), while paraoxonase-1 was maintained 1 h and elevated by 6.1% 24 h after SSE, but not HIIE (p = 0.035). In summary, FMD can be augmented by a single episode of either HIIE or SSE in moderate stages of CKD. Modest improvements were observed in antioxidant analytes, and markers of oxidative stress were blunted in response to either SSE or HIIE.
Overexpression of BQ323636.1 Modulated AR/IL-8/CXCR1 Axis to Confer Tamoxifen Resistance in ER-Positive Breast Cancer
Authors: Tsoi Ho , Shi Ling , Leung Man-Hong , Man Ellen , So Zi-Qing , Chan Wing-Lok , Khoo Ui-Soon
Published: January 2022

NCOR2 is a co-repressor for estrogen receptor (ER) and androgen receptor (AR). Our group previously identified a novel splice variant of NCOR2, BQ323636.1 (BQ), that mediates tamoxifen resistance via interference of NCOR2 repression on ER. Luciferase reporter assay showed BQ overexpression could enhance the transcriptional activity of androgen response element (ARE). We proposed that BQ employs both AR and ER to confer tamoxifen resistance. Through in silico analysis, we identified interleukin-8 (IL-8) as the sole ERE and ARE containing gene responsiveness to ER and AR activation. We confirmed that BQ overexpression enhanced the expression of IL-8 in ER+ve breast cancer cells, and AR inhibition reduced IL-8 expression in the BQ overexpressing cell lines, suggesting that AR was involved in the modulation of IL-8 expression by BQ. Moreover, we demonstrated that IL-8 could activate both AKT and ERK1/2 via CXCR1 to confer tamoxifen resistance. Targeting CXCR1/2 by a small inhibitor repertaxin reversed tamoxifen resistance of BQ overexpressing breast cancer cells in vitro and in vivo. In conclusion, BQ overexpression in ER+ve breast cancer can enhance IL-8 mediated signaling to modulate tamoxifen resistance. Targeting IL-8 signaling is a promising approach to overcome tamoxifen resistance in ER+ve breast cancer.
Invasive Fungal Infections in Under-Five Diarrheal Children: Experience from an Urban Diarrheal Disease Hospital
Authors: Shaly Nusrat Jahan , Pervez Mohammed Moshtaq , Huq Sayeeda , Ahmed Dilruba , Ahsan Chowdhury Rafiqul , Sarmin Monira , Afroze Farzana , Nuzhat Sharika , Chisti Mohammod Jobayer , Ahmed Tahmeed
Published: January 2022

Invasive fungal infections (IFIs) are opportunistic, especially in immunocompromised and hospitalized patients. Children with IFIs are more vulnerable to a fatal outcome. For early diagnosis and treatment, knowledge of the spectrum and frequency of IFIs among children is prerequisite. In this prospective observational study, we enrolled 168 children of 2–59 months old of either sex from March 2018 to December 2019 admitted to the Dhaka hospital, icddr,b. Study participants with suspected IFIs were with or without severe acute malnutrition (SAM) along with sepsis/pneumonia and fulfilled any of the following criteria: (i) failure to respond to injectable antibiotics, (ii) development of a late-onset hospital-acquired infection, (iii) needed ICU care for >7 days, (iv) took steroids/antibiotics for >2 weeks before hospitalization, and (v) developed thrush after taking injectable antibiotics. The comparison group included non-SAM (weight-for-length Z score ≥ −2) children with diarrhea and fever <3 days in the absence of co-morbidity. We performed real-time PCR, ELISA, and blood culture for the detection of fungal pathogen. Study group children with SAM, positive ELISA and PCR considered to have a IFIs. In the study group, 15/138 (10.87%) children had IFIs. Among IFIs, invasive candidiasis, aspergillosis, histoplasmosis detected in 6 (4.53%), 11 (7.97%), and 1 (0.72%) children, respectively, and (3/15 [2.17%]) children had both candidiasis and aspergillosis. Children with IFIs more often encountered septic shock (26.7% vs. 4.9%; p = 0.013) and had a higher death rate (46.7% vs. 8.9%; p < 0.001) than those without IFIs. IFIs were independently associated with female sex (OR = 3.48; 95% CI = 1.05, 11.55; p = 0.042) after adjusting for potential confounders. Our findings thus implicate that, malnourished children with septic shock require targeted screening for the early diagnosis and prompt management of IFIs that may help to reduce IFIs related deaths.
Analysis of the Increase of Vascular Cell Adhesion Molecule-1 (VCAM-1) Expression and the Effect of Exposure in a Hyperbaric Chamber on VCAM-1 in Human Blood Serum: A Cross-Sectional Study
Authors: Van Damme-Ostapowicz Katarzyna , Cybulski Mateusz , Kozakiewicz Mariusz , Krajewska-Kułak Elżbieta , Siermontowski Piotr , Sobolewski Marek , Kaczerska Dorota
Published: January 2022

Background and Objectives: Vascular cell adhesion molecule-1 (VCAM-1) was identified as a cell adhesion molecule that helps to regulate inflammation-associated vascular adhesion and the transendothelial migration of leukocytes, such as macrophages and T cells. VCAM-1 is expressed by the vascular system and can be induced by reactive oxygen species, interleukin 1 beta (IL-1β) or tumor necrosis factor alpha (TNFα), which are produced by many cell types. The newest data suggest that VCAM-1 is associated with the progression of numerous immunological disorders, such as rheumatoid arthritis, asthma, transplant rejection and cancer. The aim of this study was to analyze the increase in VCAM-1 expression and the impact of exposure in a hyperbaric chamber to VCAM-1 levels in human blood serum. Materials and Methods: The study included 92 volunteers. Blood for the tests was taken in the morning, from the basilic vein of fasting individuals, in accordance with the applicable procedure for blood collection for morphological tests. In both groups of volunteers, blood was collected before and after exposure, in heparinized tubes to obtain plasma and hemolysate, and in clot tubes to obtain serum. The level of VCAM-1 was determined using the immunoenzymatic ELISA method. Results: The study showed that the difference between the distribution of VCAM-1 before and after exposure corresponding to diving at a depth of 30 m was at the limit of statistical significance in the divers group and that, in most people, VCAM-1 was higher after exposure. Diving to a greater depth had a much more pronounced impact on changes in VCAM-1 values, as the changes observed in the VCAM-1 level as a result of diving to a depth of 60 m were statistically highly significant (p = 0.0002). The study showed an increase in VCAM-1 in relation to the baseline value, which reached as much as 80%, i.e., VCAM-1 after diving was almost twice as high in some people. There were statistically significant differences between the results obtained after exposure to diving conditions at a depth of 60 m and the values measured for the non-divers group. The leukocyte level increased statistically after exposure to 60 m. In contrast, hemoglobin levels decreased in most divers after exposure to diving at a depth of 30 m (p = 0.0098). Conclusions: Exposure in the hyperbaric chamber had an effect on serum VCAM-1 in the divers group and non-divers group. There is a correlation between the tested morphological parameters and the VCAM-1 level before and after exposure in the divers group and the non-divers group. Exposure may result in activation of the endothelium.
Influence of Reverse Osmosis Process in Different Operating Conditions on Phenolic Profile and Antioxidant Activity of Conventional and Ecological Cabernet Sauvignon Red Wine
Authors: Ivić Ivana , Kopjar Mirela , Buljeta Ivana , Pichler Dubravko , Mesić Josip , Pichler Anita
Published: January 2022

Red wine polyphenols are responsible for its colour, astringency, and bitterness. They are known as strong antioxidants that protect the human body from the harmful effects of free radicals and prevent various diseases. Wine phenolics are influenced by viticulture methods and vinification techniques, and therefore, conventionally and ecologically produced wines of the same variety do not have the same phenolic profile. Ecological viticulture avoids the use of chemical adjuvants in vineyards in order to minimise their negative influence on the environment, wine, and human health. The phenolic profile and antioxidant activity of wine can also be influenced by additional treatments, such as concentration by reverse osmosis. The aim of this study was to investigate the influence of four different pressures (2.5, 3.5, 4.5, and 5.5 MPa) and two temperature regimes (with and without cooling) on the phenolic profile and antioxidant activity of conventional and ecological Cabernet Sauvignon red wine during concentration by reverse osmosis. The results showed that retention of individual phenolic compounds depended on the applied processing parameters, chemical composition of the initial wine, and chemical properties of a compound. Higher pressure and retentate cooling favoured the retention of total polyphenols, flavonoids, and monomeric anthocyanins, compared to the opposite conditions. The same trend was observed for antioxidant activity.
Heterogeneous Microstructure-Induced Creep Failure Responses in Various Sub-Zones of Modified 310S Welded Joints
Authors: Jiang Yunlu , Kan Ying , Chen Huaining
Published: January 2022

In order to reveal the creep failure behavior of novel modified 310S austenite steel welded joints, the creep life and microstructure evolution of the 310S austenite steel welded joints were investigated in this study. The rupture life was assessed to estimate the damage of the welded joint based on creep rupture tests performed at 600 °C in the stress range of 170–238 MPa. Compared with WM, HAZ facilitated the occurrence of creep failure in long term creep due to the combination of a smaller hardness value, a more heterogenous microstructure accompanied by coarsened M23C6, a larger grain size, higher KAM and Schmid factor. Discontinuous Laves phases appeared near the boundaries between the δ-ferrite and γ-austenite grains in the WM, and dislocation strengthening and precipitation strengthening were observed near the boundary in the BM. Furthermore, segregation elements were detected by APT and EDS adjacent to the boundary. Cr and C segregation near grain boundaries weaken the creep resistance in long term creep service.
Enhanced Mechanical and Tribological Capabilities of a Silicon Aluminum Alloy with an Electroplated Ni–Co–P/Si3N4 Composite Coating
Authors: Li Zhijie , Ma Fei , Li Dongshan , Wan Shanhong , Yi Gewen , Geng Guofang , Guo Lingyan
Published: January 2022

Ni–Co–P/Si3N4 composite coatings were fabricated over an aluminum–silicon (Al–Si) substrate using a pulse-current electroplating process, in which the rapid deposition of an intermediate nickel–cobalt layer was used to improve coating adhesion. The microstructure, mechanical, and tribological behaviors of the electroplated Ni–Co–P/Si3N4 composite coating were characterized and evaluated. The results revealed that the electroplated Ni–Co–P/Si3N4 composite coating primarily consisted of highly crystalline Ni–Co sosoloid and P, and a volumetric concentration of 7.65% Si3N4. The electroplated Ni–Co–P/Si3N4 composite coating exhibited hardness values almost two times higher than the uncoated Al–Si substrate, which was comparable to hard chrome coatings. Under lubricated and dry sliding conditions, the electroplated Ni–Co–P/Si3N4 composite coating showed excellent anti-wear performance. Whether dry or lubricated with PAO and engine oil, the composite coating showed minimum abrasive wear compared to the severe adhesive wear and abrasive wear observed in the Al–Si substrate.
Understanding the Effect of Reflow Profile on the Metallurgical Properties of Tin–Bismuth Solders
Authors: Dušek Karel , Bušek David , Veselý Petr , Pražanová Anna , Plaček Martin , Re Julia Del
Published: January 2022

Sn–Bi alloys are desirable candidates for soldering components on printed circuit boards (PCBs) because of their low melting point and reduced cost. While certain tin–bismuth solders are well characterized many new alloys in this family have been developed which need proper characterization. The following study looks at the behavior of four different Sn–Bi alloys—traditional 42Sn58Bi and 42Sn57Bi1Ag and two new tin–bismuth alloys—in solder paste during the reflow soldering process. Each alloy was processed using different reflow profiles that had varying times above liquidus (TALs) and peak temperatures. The PCBs were then analyzed to see how the processing variables influenced wetting, voiding, microstructure, intermetallic layer composition, and thickness. After analysis, the PCBs were then subjected to thermal cycling experiments to see how reflow profile impacted microstructure evolution. The results demonstrated that reflow profile affects properties such as metal wetting and voiding. It does not however, greatly impact key metallurgical properties such as intermetallic layer thickness.
The Microstructure and Property of a Titanium-Carbon Steel Clad Plate Prepared Using Explosive Welding
Authors: Zhao Hui
Published: January 2022

The microstructure and properties of pure titanium (Ti)-carbon steel clad plate prepared using explosive welding were characterized. The bonding of the welding interface was inspected using C-scanning imaging technique. The microstructure and composition of the clad were characterized with optical microscopy and scanning electron microscopy. Mechanical and corrosion properties of the clad plate were investigated using tensile test, shearing test, and potentiodynamic polarization measurement. The results show that the pure titanium and carbon steel plate are joined successfully without visible defects. The interface wave is uniform. SEM observation and EDS analyses show that some melt blocks distribute at the interface waves vortices. Hardness testes results show that after heat treating, the hardness values in the titanium layer of the clad plate are similar to the original titanium plate, whereas the values at carbon steel layer increase from the interface to 300 μm away. Tensile and shearing test results indicate that the mechanical properties of the clad meet the requirements of ASTM B898 standard. Corrosion test shows that the Ecorr of the clad plate is more positive, and icorr is 1 order of magnitude lower compared to carbon steel material, suggesting that the corrosion resistance of clad plate is better than that of carbon steel material. These results suggest that the clad plate has good bonding quality and properties to meet the processing requirement and can be safely applicable in the petrochemical field.
Microenvironmental Metabolites in the Intestine: Messengers between Health and Disease
Authors: Zaurito Antonio Enrico , Tschurtschenthaler Markus
Published: January 2022

The intestinal mucosa is a highly absorptive organ and simultaneously constitutes the physical barrier between the host and a complex outer ecosystem. Intestinal epithelial cells (IECs) represent a special node that receives signals from the host and the environment and translates them into corresponding responses. Specific molecular communication systems such as metabolites are known to transmit information across the intestinal boundary. The gut microbiota or food-derived metabolites are extrinsic factors that influence the homeostasis of the intestinal epithelium, while mitochondrial and host-derived cellular metabolites determine the identity, fitness, and regenerative capacity of IECs. Little is known, however, about the role of intrinsic and extrinsic metabolites of IECs in the initiation and progression of pathological processes such as inflammatory bowel disease and colorectal cancer as well as about their impact on intestinal immunity. In this review, we will highlight the most recent contributions on the modulatory effects of intestinal metabolites in gut pathophysiology, with a particular focus on metabolites in promoting intestinal inflammation or colorectal tumorigenesis. In addition, we will provide a perspective on the role of newly identified oncometabolites from the commensal and opportunistic microbiota in shaping response and resistance to antitumor therapy.
A Cell Culture Chip with Transparent, Micropillar-Decorated Bottom for Live Cell Imaging and Screening of Breast Cancer Cells
Authors: Ermis Menekse , Antmen Ezgi , Kuren Ozgur , Demirci Utkan , Hasirci Vasif
Published: January 2022

In the recent years, microfabrication technologies have been widely used in cell biology, tissue engineering, and regenerative medicine studies. Today, the implementation of microfabricated devices in cancer research is frequent and advantageous because it enables the study of cancer cells in controlled microenvironments provided by the microchips. Breast cancer is one of the most common cancers in women, and the way breast cancer cells interact with their physical microenvironment is still under investigation. In this study, we developed a transparent cell culture chip (Ch-Pattern) with a micropillar-decorated bottom that makes live imaging and monitoring of the metabolic, proliferative, apoptotic, and morphological behavior of breast cancer cells possible. The reason for the use of micropatterned surfaces is because cancer cells deform and lose their shape and acto-myosin integrity on micropatterned substrates, and this allows the quantification of the changes in morphology and through that identification of the cancerous cells. In the last decade, cancer cells were studied on micropatterned substrates of varying sizes and with a variety of biomaterials. These studies were conducted using conventional cell culture plates carrying patterned films. In the present study, cell culture protocols were conducted in the clear-bottom micropatterned chip. This approach adds significantly to the current knowledge and applications by enabling low-volume and high-throughput processing of the cell behavior, especially the cell–micropattern interactions. In this study, two different breast cancer cell lines, MDA-MB-231 and MCF-7, were used. MDA-MB-231 cells are invasive and metastatic, while MCF-7 cells are not metastatic. The nuclei of these two cell types deformed to distinctly different levels on the micropatterns, had different metabolic and proliferation rates, and their cell cycles were affected. The Ch-Pattern chips developed in this study proved to have significant advantages when used in the biological analysis of live cells and highly beneficial in the study of screening breast cancer cell–substrate interactions in vitro.
Molecular Recognition by Silicon Nanowire Field-Effect Transistor and Single-Molecule Force Spectroscopy
Authors: Espinosa Francisco , Uhlig Manuel , Garcia Ricardo
Published: January 2022

Silicon nanowire (SiNW) field-effect transistors (FETs) have been developed as very sensitive and label-free biomolecular sensors. The detection principle operating in a SiNW biosensor is indirect. The biomolecules are detected by measuring the changes in the current through the transistor. Those changes are produced by the electrical field created by the biomolecule. Here, we have combined nanolithography, chemical functionalization, electrical measurements and molecular recognition methods to correlate the current measured by the SiNW transistor with the presence of specific molecular recognition events on the surface of the SiNW. Oxidation scanning probe lithography (o-SPL) was applied to fabricate sub-12 nm SiNW field-effect transistors. The devices were applied to detect very small concentrations of proteins (500 pM). Atomic force microscopy (AFM) single-molecule force spectroscopy (SMFS) experiments allowed the identification of the protein adsorption sites on the surface of the nanowire. We detected specific interactions between the biotin-functionalized AFM tip and individual avidin molecules adsorbed to the SiNW. The measurements confirmed that electrical current changes measured by the device were associated with the deposition of avidin molecules.
Antimicrobial Susceptibility of Clinical Oral Isolates of Actinomyces spp.
Authors: Wolff Alexandra , Rodloff Arne C. , Vielkind Paul , Borgmann Toralf , Stingu Catalina-Suzana
Published: January 2022

Actinomyces species play an important role in the pathogenesis of oral diseases and infections. Susceptibility testing is not always routinely performed, and one may oversee a shift in resistance patterns. The aim of the study was to analyze the antimicrobial susceptibility of 100 well-identified clinical oral isolates of Actinomyces spp. against eight selected antimicrobial agents using the agar dilution (AD) and E-Test (ET) methods. We observed no to low resistance against penicillin, ampicillin-sulbactam, meropenem, clindamycin, linezolid and tigecycline (0–2% ET, 0% AD) but high levels of resistance to moxifloxacin (93% ET, 87% AD) and daptomycin (83% ET, 95% AD). The essential agreement of the two methods was very good for benzylpenicillin (EA 95%) and meropenem (EA 92%). The ET method was reliable for correctly categorizing susceptibility, in comparison with the reference method agar dilution, except for daptomycin (categorical agreement 87%). Penicillin is still the first-choice antibiotic for therapy of diseases caused by Actinomyces spp.