bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes of Extreme Agro-Climatic Droughts and Their Impacts on Grain Yields in Rain-Fed Agricultural Regions in China over the Past 50 Years
Authors: Liu Min , Guo Ying , Wang Yanfang , Hao Jing
Published: December 2021

Climate change and climate extremes and their impacts on agriculture, water resources, and ecosystems have become important issues globally. Agricultural sustainability and food security are facing unprecedented challenges due to the increasing occurrence of extreme climatic events, including, notably, extreme droughts in recent years in China. In this study, a threshold determination model of extreme agro-climatic droughts (EADs) was built based on the cumulative probability distribution functions (CDF) of an agricultural drought index—the consecutive days without available precipitation (CDWAP). The CDWAP was established by combining meteorological data with the characteristics of cropping patterns and the water requirement in different growing periods of crops. The CDF of CDWAP was obtained based on the relationship of CDWAP and its occurrence frequency. Based on the model, the spatial pattern of the thresholds of EADs and the threshold exceedance time series of EADs in 500 meteorological stations were obtained, and then changes in the frequencies and intensities of EADs in China and their impacts on grain yields in rain-fed regions during the past 50 years were analyzed. The results follow: (1) The threshold value of EADs in China gradually increased from southeast to northwest. The stations of the highest value were located in the Northwest China, with the CDWAP more than 60 days, while the lowest value was in the middle reaches of the Yangzi River, with the CDWAP less than 16 days. (2) The frequencies and intensities of the EADs increased mostly in the east areas of the Hu Huanyong line, which was also the main agricultural production region in China. The North China (NC) and Southwest China (SW) regions showed the highest increasing rates of the EADs; their frequencies and intensities were 11.3% and 2.2%, respectively, for the NC region, and 9.3% and 2.7%, respectively, for the SW region. (3) Case studies in the NC, SW, and SE regions indicated that there was a negative correlation between grain yields and EAD frequency and intensity; i.e., the low grain yields often occurred in the year with relatively higher frequency or/and stronger intensity of EADs. The correlation coefficients of grain yield and EAD were generally greater than that of merely extreme climatic droughts; therefore, the study of EAD is necessary when researching the impacts of extreme drought events on grain yield.
The Space and Terrestrial Weather Variations as Possible Factors for Ischemia Events in Saint Petersburg
Authors: Stupishina Olga M. , Golovina Elena G. , Noskov Sergei N. , Eremin Gennady B. , Gorbanev Sergei A.
Published: December 2021

The Space and Terrestrial Weather (Weather Complex) impact on ischemia cases in Saint Petersburg is investigated. The results show the main feature of the Weather Complex when it was related to the days of the different ischemia situations in the different ischemia people gender groups. The data treatment was done with some elements of the Folder Epochs Method, Cluster Analysis and the Mann–Whitney hypothesis test criterion.
Interdisciplinary Approaches to the Study of Listening Effort in Young Children with Cochlear Implants
Authors: Saksida Amanda , Ghiselli Sara , Bembich Stefano , Scorpecci Alessandro , Giannantonio Sara , Resca Alessandra , Marsella Pasquale , Orzan Eva
Published: December 2021

Very early bilateral implantation is thought to significantly reduce the attentional effort required to acquire spoken language, and consequently offer a profound improvement in quality of life. Despite the early intervention, however, auditory and communicative outcomes in children with cochlear implants remain poorer than in hearing children. The distorted auditory input via the cochlear implants requires more auditory attention resulting in increased listening effort and fatigue. Listening effort and fatigue may critically affect attention to speech, and in turn language processing, which may help to explain the variation in language and communication abilities. However, measuring attention to speech and listening effort is demanding in infants and very young children. Three objective techniques for measuring listening effort are presented in this paper that may address the challenges of testing very young and/or uncooperative children with cochlear implants: pupillometry, electroencephalography, and functional near-infrared spectroscopy. We review the studies of listening effort that used these techniques in paediatric populations with hearing loss, and discuss potential benefits of the systematic evaluation of listening effort in these populations.
Symmetric Aqueous Batteries of Titanium Hexacyanoferrate in Na+, K+, and Mg2+ Media
Authors: Li Min , Bina Alessandro , Maisuradze Mariam , Giorgetti Marco
Published: December 2021

Symmetric batteries, in which the same active material is used for the positive and the negative electrode, simplifying the manufacture process and reducing the fabrication cost, have attracted extensive interest for large-scale stationary energy storage. In this paper, we propose a symmetric battery based on titanium hexacyanoferrate (TiHCF) with two well-separated redox peaks of Fe3+/Fe2+ and Ti4+/Ti3+ and tested it in aqueous Na-ion/ K-ion/Mg-ion electrolytes. The result shows that all the symmetric batteries exhibit a voltage plateau centered at around 0.6 V, with discharge capacity around 30 mAhg−1 at C/5. Compared to a Mg-ion electrolyte, the TiHCF symmetric batteries in Na-ion and K-ion electrolytes have better stability. The calculated diffusion coefficient of Na+, K+, and Mg2+ are in the same order of magnitude, which indicates that the three-dimensional ionic channels and interstices in the lattice of TiHCF are large enough for an efficient Na+, K+ and Mg2+ insertion and extraction.
Sheep β-Defensin 2 Regulates Escherichia coli F17 Resistance via NF-κB and MAPK Signaling Pathways in Ovine Intestinal Epithelial Cells
Authors: Ge Ling , Zou Shuangxia , Yuan Zehu , Chen Weihao , Wang Shanhe , Cao Xiukai , Lv Xiaoyang , Getachew Tesfaye , Mwacharo Joram M. , Haile Aynalem , Sun Wei
Published: December 2021

Escherichia coli (E. coli) F17 is a member of enterotoxigenic Escherichia coli, which can cause massive diarrhea and high mortality in newborn lambs. β-defensin is mainly produced by the epithelial tissue of the gastrointestinal tract in response to microbial infection. However, the molecular mechanism of sheep β-defensin 2 (SBD-2) against E. coli F17 remains unclear. This study aims to reveal the antibacterial ability of SBD-2 against E. coli F17 infection in sheep. Firstly, we established the culture system of ovine intestinal epithelial cells (OIECs) in vitro, treated with different concentrations of E. coli F17 for an indicated time. Secondly, we performed RNA interference and overexpression to investigate the effect of SBD-2 expression on E. coli F17 adhesion to OIECs. Finally, inhibitors of NF-κB and MAPK pathways were pre-treated to explore the possible relationship involving in E. coli F17 infection regulating SBD-2 expression. The results showed that E. coli F17 markedly (p < 0.01) upregulated the expression levels of SBD-2 mRNA and protein in a concentration- and time-dependent manner. Overexpression of SBD-2 contributed to enhancing E. coli F17 resistance in OIECs, while silencing SBD-2 dramatically improved the adhesion of E. coli F17 to OIECs (p < 0.05 or p < 0.01). Furthermore, E. coli F17 stimulated SBD-2 expression was obviously decreased by pre-treatment with NF-κB inhibitor PDTC, p38 MAPK inhibitor SB202190 and ERK1/2 MAPK inhibitor PD98095 (p < 0.05 or p < 0.01). Interestingly, adhesion of E. coli F17 to OIECs were highly enhanced by pre-treated with PDTC, SB202190 and PD98095. Our data suggested that SBD-2 could inhibit E. coli F17 infection in OIECs, possibly through NF-κB and MAPK signaling pathways. Our results provide useful theoretical basis on developing anti-infective drug and breeding for E. coli diarrhea disease-resistant sheep.
Virus Mimetic Poly (I:C)-Primed Airway Exosome-like Particles Enter Brain and Induce Inflammatory Cytokines and Mitochondrial Reactive Oxygen Species in Microglia
Authors: Kulakauskienė Deimantė , Narauskaitė Deimantė , Gečys Dovydas , Juknaitė Otilija , Jankauskaitė Lina , Masaitytė Aistė , Šventoraitienė Jurgita , Inokaitis Hermanas , Miknienė Zoja , Sadauskienė Ilona , Steponaitis Giedrius , Balion Zbigniev , Morkūnienė Ramunė , Paužienė Neringa , Pauža Dainius Haroldas , Jekabsone Aistė
Published: December 2021

Viral infections induce extracellular vesicles (EVs) containing viral material and inflammatory factors. Exosomes can easily cross the blood-brain barrier during respiratory tract infection and transmit the inflammatory signal to the brain; however, such a hypothesis has no experimental evidence. The study investigated whether exosome-like vesicles (ELVs) from virus mimetic poly (I:C)-primed airway cells enter the brain and interact with brain immune cells microglia. Airway cells were isolated from Wistar rats and BALB/c mice; microglial cell cultures—from Wistar rats. ELVs from poly (I:C)-stimulated airway cell culture medium were isolated by precipitation, visualised by transmission electron microscopy, and evaluated by nanoparticle analyser; exosomal markers CD81 and CD9 were determined by ELISA. For in vitro and in vivo tracking, particles were loaded with Alexa Fluor 555-labelled RNA. Intracellular reactive oxygen species (ROS) were evaluated by DCFDA fluorescence and mitochondrial superoxide—by MitoSOX. ELVs from poly (I:C)-primed airway cells entered the brain within an hour after intranasal introduction, were internalised by microglia and induced intracellular and intramitochondrial ROS production. There was no ROS increase in microglial cells was after treatment with ELVs from airway cells untreated with poly (I:C). In addition, poly (I:C)-primed airway cells induced inflammatory cytokine expression in the brain. The data indicate that ELVs secreted by virus-primed airway cells might enter the brain, cause the activation of microglial cells and neuroinflammation.
Controlled Synthesis of Up-Conversion NaYF4:Yb,Tm Nanoparticles for Drug Release under Near IR-Light Therapy
Authors: Moyano Rodríguez Edelweiss , Gomez-Mendoza Miguel , Pérez-Ruiz Raúl , Peñín Beatriz , Sampedro Diego , Caamaño Antonio , de la Peña O’Shea Víctor A.
Published: December 2021

Up-Conversion materials have received great attention in drug delivery applications in recent years. A specifically emerging field includes the development of strategies focusing on photon processes that promote the development of novel platforms for the efficient transport and the controlled release of drug molecules in the harsh microenvironment. Here, modified reaction time, thermal treatment, and pH conditions were controlled in the synthesis of NaYF4:Yb,Tm up-converted (UC) material to improve its photoluminescence properties. The best blue-emission performance was achieved for the UC3 sample prepared through 24 h-synthesis without thermal treatment at a pH of 5, which promotes the presence of the β-phase and smaller particle size. NaYF4:Yb,Tm has resulted in a highly efficient blue emitter material for light-driven drug release under near-IR wavelength. Thus, NaYF4:Yb,Tm up-converted material promotes the N-O bond cleavage of the oxime ester of Ciprofloxacin (prodrug) as a highly efficient photosensitized drug delivery process. HPLC chromatography and transient absorption spectroscopy measurements were performed to evaluate the drug release conversion rate. UC3 has resulted in a very stable and easily recovered material that can be used in several reaction cycles. This straightforward methodology can be extended to other drugs containing photoactive chromophores and is present as an alternative for drug release systems.
Butyrate Protects against Diet-Induced NASH and Liver Fibrosis and Suppresses Specific Non-Canonical TGF-β Signaling Pathways in Human Hepatic Stellate Cells
Authors: Gart Eveline , van Duyvenvoorde Wim , Toet Karin , Caspers Martien P. M. , Verschuren Lars , Nielsen Mette Juul , Leeming Diana Julie , Souto Lima Everton , Menke Aswin , Hanemaaijer Roeland , Keijer Jaap , Salic Kanita , Kleemann Robert , Morrison Martine C.
Published: December 2021

In obesity-associated non-alcoholic steatohepatitis (NASH), persistent hepatocellular damage and inflammation are key drivers of fibrosis, which is the main determinant of NASH-associated mortality. The short-chain fatty acid butyrate can exert metabolic improvements and anti-inflammatory activities in NASH. However, its effects on NASH-associated liver fibrosis remain unclear. Putative antifibrotic effects of butyrate were studied in Ldlr-/-.Leiden mice fed an obesogenic diet (HFD) containing 2.5% (w/w) butyrate for 38 weeks and compared with a HFD-control group. Antifibrotic mechanisms of butyrate were further investigated in TGF-β-stimulated primary human hepatic stellate cells (HSC). HFD-fed mice developed obesity, insulin resistance, increased plasma leptin levels, adipose tissue inflammation, gut permeability, dysbiosis, and NASH-associated fibrosis. Butyrate corrected hyperinsulinemia, lowered plasma leptin levels, and attenuated adipose tissue inflammation, without affecting gut permeability or microbiota composition. Butyrate lowered plasma ALT and CK-18M30 levels and attenuated hepatic steatosis and inflammation. Butyrate inhibited fibrosis development as demonstrated by decreased hepatic collagen content and Sirius-red-positive area. In TGF-β-stimulated HSC, butyrate dose-dependently reduced collagen deposition and decreased procollagen1α1 and PAI1 protein expression. Transcriptomic analysis and subsequent pathway and upstream regulator analysis revealed deactivation of specific non-canonical TGF-β signaling pathways Rho-like GTPases and PI3K/AKT and other important pro-fibrotic regulators (e.g., YAP/TAZ, MYC) by butyrate, providing a potential rationale for its antifibrotic effects. In conclusion, butyrate protects against obesity development, insulin resistance-associated NASH, and liver fibrosis. These antifibrotic effects are at least partly attributable to a direct effect of butyrate on collagen production in hepatic stellate cells, involving inhibition of non-canonical TGF-β signaling pathways.
Improving Biosensors by the Use of Different Nanomaterials: Case Study with Microcystins as Target Analytes
Authors: Park Hanbin , Kim Gahyeon , Seo Yoseph , Yoon Yejin , Min Junhong , Park Chulhwan , Lee Taek
Published: December 2021

The eutrophication of lakes and rivers without adequate rainfall leads to excessive growth of cyanobacterial harmful algal blooms (CyanoHABs) that produce toxicants, green tides, and unpleasant odors. The rapid growth of CyanoHABs owing to global warming, climate change, and the development of rainforests and dams without considering the environmental concern towards lakes and rivers is a serious issue. Humans and livestock consuming the toxicant-contaminated water that originated from CyanoHABs suffer severe health problems. Among the various toxicants produced by CyanoHABs, microcystins (MCs) are the most harmful. Excess accumulation of MC within living organisms can result in liver failure and hepatocirrhosis, eventually leading to death. Therefore, it is essential to precisely detect MCs in water samples. To date, the liquid chromatography–mass spectrometry (LC–MS) and enzyme-linked immunosorbent assay (ELISA) have been the standard methods for the detection of MC and provide precise results with high reliability. However, these methods require heavy instruments and complicated operation steps that could hamper the portability and field-readiness of the detection system. Therefore, in order for this goal to be achieved, the biosensor has been attracted to a powerful alternative for MC detection. Thus far, several types of MC biosensor have been proposed to detect MC in freshwater sample. The introduction of material is a useful option in order to improve the biosensor performance and construct new types of biosensors. Introducing nanomaterials to the biosensor interface provides new phenomena or enhances the sensitivity. In recent times, different types of nanomaterials, such as metallic, carbon-based, and transition metal dichalcogenide-based nanomaterials, have been developed and used to fabricate biosensors for MC detection. This study reviews the recent advancements in different nanomaterial-based MC biosensors.
Pressure-Free Assembling of Poly(methyl methacrylate) Microdevices via Microwave-Assisted Solvent Bonding and Its Biomedical Applications
Authors: Trinh Kieu The Loan , Chae Woo Ri , Lee Nae Yoon
Published: December 2021

Poly(methyl methacrylate) (PMMA) has become an appealing material for manufacturing microfluidic chips, particularly for biomedical applications, because of its transparency and biocompatibility, making the development of an appropriate bonding strategy critical. In our research, we used acetic acid as a solvent to create a pressure-free assembly of PMMA microdevices. The acetic acid applied between the PMMA slabs was activated by microwave using a household microwave oven to tightly merge the substrates without external pressure such as clamps. The bonding performance was tested and a superior bond strength of 14.95 ± 0.77 MPa was achieved when 70% acetic acid was used. Over a long period, the assembled PMMA device with microchannels did not show any leakage. PMMA microdevices were also built as a serpentine 2D passive micromixer and cell culture platform to demonstrate their applicability. The results demonstrated that the bonding scheme allows for the easy assembly of PMMAs with a low risk of clogging and is highly biocompatible. This method provides for a simple but robust assembly of PMMA microdevices in a short time without requiring expensive instruments.
Maximizing the Surface Sensitivity of LSPR Biosensors through Plasmon Coupling—Interparticle Gap Optimization for Dimers Using Computational Simulations
Authors: Bonyár Attila
Published: December 2021

The bulk and surface refractive index sensitivities of LSPR biosensors, consisting of coupled plasmonic nanosphere and nano-ellipsoid dimers, were investigated by simulations using the boundary element method (BEM). The enhancement factor, defined as the ratio of plasmon extinction peak shift of multi-particle and single-particle arrangements caused by changes in the refractive index of the environment, was used to quantify the effect of coupling on the increased sensitivity of the dimers. The bulk refractive index sensitivity (RIS) was obtained by changing the dielectric medium surrounding the nanoparticles, while the surface sensitivity was modeled by depositing dielectric layers on the nanoparticle in an increasing thickness. The results show that by optimizing the interparticle gaps for a given layer thickness, up to ~80% of the optical response range of the nanoparticles can be utilized by confining the plasmon field between the particles, which translates into an enhancement of ~3–4 times compared to uncoupled, single particles with the same shape and size. The results also show that in these cases, the surface sensitivity enhancement is significantly higher than the bulk RI sensitivity enhancement (e.g., 3.2 times vs. 1.8 times for nanospheres with a 70 nm diameter), and thus the sensors’ response for molecular interactions is higher than their RIS would indicate. These results underline the importance of plasmonic coupling in the optimization of nanoparticle arrangements for biosensor applications. The interparticle gap should be tailored with respect to the size of the used receptor/target molecules to maximize the molecular sensitivity, and the presented methodology can effectively aid the optimization of fabrication technologies.
Early Pupillometry Assessment in Traumatic Brain Injury Patients: A Retrospective Study
Authors: Luz Teixeira Thomas , Peluso Lorenzo , Banco Pierluigi , Njimi Hassane , Abi-Khalil Layal , Chanchay Pillajo Mélanie , Schuind Sophie , Creteur Jacques , Bouzat Pierre , Taccone Fabio Silvio
Published: December 2021

Background: The aim of this study was to evaluate whether the early assessment of neurological pupil index (NPi) values derived from automated pupillometry could predict neurological outcome after traumatic brain injury (TBI). Methods: Retrospective observational study including adult (>18 years) TBI patients admitted from January 2018 to December 2020, with available NPi on admission. Abnormal NPi was considered if <3. Unfavorable neurological outcome (UO) at hospital discharge was considered for a Glasgow Outcome Scale of 1–3. Results: 100 patients were included over the study period (median age 48 (34–69) years and median GCS on admission 11 (6–15)); 49 (49%) patients had UO. On admission, 20 (20%) patients had an abnormal NPi (NPi < 3); median worst (i.e., from both eyes) NPi was 4.2 (3.2–4.5). Median worst and mean NPi on admission were significantly lower in the UO group than others (3.9 (1.7–4.4) vs. 4.4 (3.7–4.6); p = 0.005–4.0 (2.6–4.5) vs. 4.5 (3.9–4.7); p = 0.002, respectively). The ROC curve for the worst and mean NPi showed a moderate accuracy to predict UO (AUC 0.66 (0.56–0.77); p = 0.005 and 0.68 (0.57–0.78); p = 0.002). However, in a generalized linear model, the prognostic role of NPi on admission was limited. Conclusions: Low NPi on admission has limited prognostic value in TBI.
Self-Awareness of Soviet Lithuanian Architects in Their Creative Power and Social Significance
Authors: Dijokienė Dalia , Navickienė Eglė , Riaubienė Edita
Published: December 2021

The field of contemporary Lithuanian architecture is influenced by architects from different periods with different attitudes. This is manifested by increasing miscommunication between generations of architects and a crisis of values. Various tensions in the community of architects triggered the idea to look to the past and examine the self-awareness of professional architects in Soviet society. In this study, we delved into their understanding of the architect’s mission, role, status, and significance in society through their expectations, powers, impact, and perceived responsibility. This study is based on semi-structured in-depth interviews with 9prominent and influential architects who received their professional education in post-war Lithuania and were actively working in the Soviet period (1955–1990) and later. In general, Lithuanian architects managed to withstand Soviet doctrine and remained loyal to Western cultural values. The study’s findings reveal five components of the architect’s self-awareness, which define the dual scope of this field, where architects perform their direct professional tasks and where they express themselves as people of culture. The self-awareness crisis becomes prominent in the main axis of the architect’s choice of art creator vs. service provider, where Lithuanian modernists position themselves as artist–creator’, leading to frustration regarding the current reality.
Differential Expression of Polyamine Pathways in Human Pancreatic Tumor Progression and Effects of Polyamine Blockade on Tumor Microenvironment
Authors: Nakkina Sai , Gitto Sarah , Pandey Veethika , Parikh Jignesh , Geerts Dirk , Maurer Hans , Olive Kenneth , Phanstiel Otto , Altomare Deborah
Published: December 2021

Pancreatic cancer is the fourth leading cause of cancer death. Existing therapies only moderately improve pancreatic ductal adenocarcinoma (PDAC) patient prognosis. The present study investigates the importance of the polyamine metabolism in the pancreatic tumor microenvironment. Relative mRNA expression analysis identified differential expression of polyamine biosynthesis, homeostasis, and transport mediators in both pancreatic epithelial and stromal cells from low-grade pancreatic intraepithelial neoplasia (PanIN-1) or primary PDAC patient samples. We found dysregulated mRNA levels that encode for proteins associated with the polyamine pathway of PDAC tumors compared to early lesions. Next, bioinformatic databases were used to assess expression of select genes involved in polyamine metabolism and their impact on patient survival. Higher expression of pro-polyamine genes was associated with poor patient prognosis, supporting the use of a polyamine blockade therapy (PBT) strategy for inhibiting pancreatic tumor progression. Moreover, PBT treatment of syngeneic mice injected intra-pancreatic with PAN 02 tumor cells resulted in increased survival and decreased tumor weights of PDAC-bearing mice. Histological assessment of PBT-treated tumors revealed macrophage presence and significantly increased expression of CD86, a T cell co-stimulatory marker. Collectively, therapies which target polyamine metabolism can be used to disrupt tumor progression, modulate tumor microenvironment, and extend overall survival.
The Tubulin Code and Tubulin-Modifying Enzymes in Autophagy and Cancer
Authors: Trisciuoglio Daniela , Degrassi Francesca
Published: December 2021

Microtubules are key components of the cytoskeleton of eukaryotic cells. Microtubule dynamic instability together with the “tubulin code” generated by the choice of different α- and β- tubulin isoforms and tubulin post-translational modifications have essential roles in the control of a variety of cellular processes, such as cell shape, cell motility, and intracellular trafficking, that are deregulated in cancer. In this review, we will discuss available evidence that highlights the crucial role of the tubulin code in determining different cancer phenotypes, including metastatic cell migration, drug resistance, and tumor vascularization, and the influence of modulating tubulin-modifying enzymes on cancer cell survival and aggressiveness. We will also discuss the role of post-translationally modified microtubules in autophagy—the lysosomal-mediated cellular degradation pathway—that exerts a dual role in many cancer types, either promoting or suppressing cancer growth. We will give particular emphasis to the role of tubulin post-translational modifications and their regulating enzymes in controlling the different stages of the autophagic process in cancer cells, and consider how the experimental modulation of tubulin-modifying enzymes influences the autophagic process in cancer cells and impacts on cancer cell survival and thereby represents a new and fruitful avenue in cancer therapy.
Evaluation of Changes to the Oral Microbiome Based on 16S rRNA Sequencing among Children Treated for Cancer
Authors: Proc Patrycja , Szczepańska Joanna , Zarzycka Beata , Szybka Małgorzata , Borowiec Maciej , Płoszaj Tomasz , Fendler Wojciech , Chrzanowski Jędrzej , Zubowska Małgorzata , Stolarska Małgorzata , Młynarski Wojciech
Published: December 2021

A child’s mouth is the gateway to many species of bacteria. Changes in the oral microbiome may affect the health of the entire body. The aim of the study was to evaluate the changes in the oral microbiome of childhood cancer survivors. Saliva samples before and after anti-cancer treatment were collected from 20 patients aged 6–18 years, diagnosed de novo with cancer in 2018–2019 (7 girls and 13 boys, 7.5–19 years old at the second time point). Bacterial DNA was extracted, and the microbial community profiles were assessed by 16S rRNA sequencing. The relative abundances of Cellulosilyticum and Tannerella genera were found to significantly change throughout therapy (p = 0.043 and p = 0.036, respectively). However, no differences in the alpha-diversity were observed (p = 0.817). The unsupervised classification revealed two clusters of patients: the first with significant changes in Campylobacter and Fusobacterium abundance, and the other with change in Neisseria. These two groups of patients differed in median age (10.25 vs. 16.16 years; p = 0.004) and the length of anti-cancer therapy (19 vs. 4 months; p = 0.003), but not cancer type or antibiotic treatment.
Immune-Proteome Profiling in Classical Hodgkin Lymphoma Tumor Diagnostic Tissue
Authors: Gholiha Alex Reza , Hollander Peter , Löf Liza , Larsson Anders , Hashemi Jamileh , Ulfstedt Johan Mattsson , Molin Daniel , Amini Rose-Marie , Freyhult Eva , Kamali-Moghaddam Masood , Enblad Gunilla
Published: December 2021

In classical Hodgkin Lymphoma (cHL), immunoediting via protein signaling is key to evading tumor surveillance. We aimed to identify immune-related proteins that distinguish diagnostic cHL tissues (=diagnostic tumor lysates, n = 27) from control tissues (reactive lymph node lysates, n = 30). Further, we correlated our findings with the proteome plasma profile between cHL patients (n = 26) and healthy controls (n = 27). We used the proximity extension assay (PEA) with the OlinkTM multiplex Immuno-Oncology panel, consisting of 92 proteins. Univariate, multivariate-adjusted analysis and Benjamini–Hochberg’s false discovery testing (=Padj) were performed to detect significant discrepancies. Proteins distinguishing cHL cases from controls were more numerous in plasma (30 proteins) than tissue (17 proteins), all Padj < 0.05. Eight of the identified proteins in cHL tissue (PD-L1, IL-6, CCL17, CCL3, IL-13, MMP12, TNFRS4, and LAG3) were elevated in both cHL tissues and cHL plasma compared with control samples. Six proteins distinguishing cHL tissues from controls tissues were significantly correlated to PD-L1 expression in cHL tissue (IL-6, MCP-2, CCL3, CCL4, GZMB, and IFN-gamma, all p ≤0.05). In conclusion, this study introduces a distinguishing proteomic profile in cHL tissue and potential immune-related markers of pathophysiological relevance.
Technological Aspects of Highly Selective Synthesis of Allyloxyalcohols—New, Greener, Productive Methods
Authors: Urbala Magdalena
Published: December 2021

Allyl ethers bearing free hydroxyl groups of CH2=CH-CH-O-A-OH type (hydroxyalkyl allyl ethers, allyloxyalcohols) are valuable chemicals in many environmentally friendly industrial applications. The development of technologically attractive methods for their production is necessary. The two pathways (L-L PTC and non-catalytic solvent-free conditions) were optimized for the highly selective and yield synthesis of 4-allyloxybutan-1-ol. Improvements in the PTC method (50% NaOH(aq), the equimolar ratio of NaOH to diol, cyclohexane as solvent) with a new highly selective and effective PT catalyst, i.e., Me(n-Oct)3N+Br− (0.3 mol%), resulted in 88% yield and 98% selectivity of 4-allyloxybutan-1-ol with minimal formation of allyl chloride hydrolysis by-products (<1%). In turn, application of non-catalytic solvent-free conditions and the change in the key substrate with an excess of diol and use of solid NaOH solely led to a mono-O-allylation product with an excellent yield of 99% in a relatively short reaction time (3.5 h), with trace amounts of by-products (<0.1%). This sustainable method is perfectly suitable for the synthesis on a larger scale (3 moles of the key substrate) and for the full O-allylation process.
Defucosylated Mouse–Dog Chimeric Anti-EGFR Antibody Exerts Antitumor Activities in Mouse Xenograft Models of Canine Tumors
Authors: Li Guanjie , Ohishi Tomokazu , Kaneko Mika K. , Takei Junko , Mizuno Takuya , Kawada Manabu , Saito Masaki , Suzuki Hiroyuki , Kato Yukinari
Published: December 2021

The epidermal growth factor receptor (EGFR) contributes to tumor malignancy via gene amplification and protein overexpression. Previously, we developed an anti-human EGFR (hEGFR) monoclonal antibody, namely EMab-134, which detects hEGFR and dog EGFR (dEGFR) with high sensitivity and specificity. In this study, we produced a defucosylated mouse–dog chimeric anti-EGFR monoclonal antibody, namely E134Bf. In vitro analysis revealed that E134Bf highly exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against a canine osteosarcoma cell line (D-17) and a canine fibroblastic cell line (A-72), both of which express endogenous dEGFR. Moreover, in vivo administration of E134Bf significantly suppressed the development of D-17 and A-72 compared with the control dog IgG in mouse xenografts. These results indicate that E134Bf exerts antitumor effects against dEGFR-expressing canine cancers and could be valuable as part of an antibody treatment regimen for dogs.
Immunoglobulin A Mucosal Immunity and Altered Respiratory Epithelium in Cystic Fibrosis
Authors: Gohy Sophie , Moeremans Alexandra , Pilette Charles , Collin Amandine
Published: December 2021

The respiratory epithelium represents the first chemical, immune, and physical barrier against inhaled noxious materials, particularly pathogens in cystic fibrosis. Local mucus thickening, altered mucociliary clearance, and reduced pH due to CFTR protein dysfunction favor bacterial overgrowth and excessive inflammation. We aimed in this review to summarize respiratory mucosal alterations within the epithelium and current knowledge on local immunity linked to immunoglobulin A in patients with cystic fibrosis.
The Cross-Talk between Myeloid and Mesenchymal Stem Cells of Human Bone Marrow Represents a Biomarker of Aging That Regulates Immune Response and Bone Reabsorption
Authors: Perico Maria Elisa , Maluta Tommaso , Conti Giamaica , Vella Antonio , Provezza Lisa , Cestari Tiziana , De Cao Giulia , Segalla Lydia , Tecchio Cristina , Benedetti Fabio , Santini Francesco , Bronte Vincenzo , Magnan Bruno , Sbarbati Andrea , Ramarli Dunia
Published: December 2021

One of the mechanisms that characterizes the aging process of different organs is the accumulation of fat. Different authors have demonstrated that adipose tissue replaces the loss of other cell types, deriving from mesenchymal cells. During aging, there is substitution or trans-differentiation of mesenchymal cells with other cells having the same embryological origin. Newly formed adipocytes were also observed in the trabecular matrix of elderly people’s bones, associated with myeloid cells. In this study, we have investigated the relationship between immature myeloid-derived suppressor cells (I-MDSCs) and mesenchymal stem cells (MSCs) in bone marrow (BM) samples harvested from 57 patients subjected to different orthopedic surgeries. Patients aged from 18 to 92 years were considered in order to compare the cellular composition of bone marrow of young and elderly people, considered a biomarker of immunity, inflammation, and bone preservation. The I-MDSC percentage was stable during aging, but in elderly people, it was possible to observe a strong basal immunosuppression of autologous and heterologous T cells’ proliferation. We hypothesized that this pattern observed in elders depends on the progressive accumulation in the BM of activating stimuli, including cell–cell contact, or the production of different cytokines and proteins that induce the differentiation of bone marrow mesenchymal stem cells in adipocytes. The collected data provided underline the importance of specific biomarkers of aging that promote a reduction in immune response and incremented inflammatory pathways, leading to bone reabsorption in elderly people.
Structural and Functional Characterization of a Novel Recombinant Antimicrobial Peptide from Hermetia illucens
Authors: Di Somma Angela , Moretta Antonio , Cané Carolina , Scieuzo Carmen , Salvia Rosanna , Falabella Patrizia , Duilio Angela
Published: December 2021

Antibiotics are commonly used to treat pathogenic bacteria, but their prolonged use contributes to the development and spread of drug-resistant microorganisms raising the challenge to find new alternative drugs. Antimicrobial peptides (AMPs) are small/medium molecules ranging 10–60 residues synthesized by all living organisms and playing important roles in the defense systems. These features, together with the inability of microorganisms to develop resistance against the majority of AMPs, suggest that these molecules might represent effective alternatives to classical antibiotics. Because of their high biodiversity, with over one million described species, and their ability to live in hostile environments, insects represent the largest source of these molecules. However, production of insect AMPs in native forms is challenging. In this work we investigate a defensin-like antimicrobial peptide identified in the Hermetia illucens insect through a combination of transcriptomics and bioinformatics approaches. The C-15867 AMP was produced by recombinant DNA technology as a glutathione S-transferase (GST) fusion peptide and purified by affinity chromatography. The free peptide was then obtained by thrombin proteolysis and structurally characterized by mass spectrometry and circular dichroism analyses. The antibacterial activity of the C-15867 peptide was evaluated in vivo by determination of the minimum inhibitory concentration (MIC). Finally, crystal violet assays and SEM analyses suggested disruption of the cell membrane architecture and pore formation with leaking of cytosolic material.
Analyzing the Applicability of Random Forest-Based Models for the Forecast of Run-of-River Hydropower Generation
Authors: Sessa Valentina , Assoumou Edi , Bossy Mireille , Simões Sofia G.
Published: December 2021

Analyzing the impact of climate variables into the operational planning processes is essential for the robust implementation of a sustainable power system. This paper deals with the modeling of the run-of-river hydropower production based on climate variables on the European scale. A better understanding of future run-of-river generation patterns has important implications for power systems with increasing shares of solar and wind power. Run-of-river plants are less intermittent than solar or wind but also less dispatchable than dams with storage capacity. However, translating time series of climate data (precipitation and air temperature) into time series of run-of-river-based hydropower generation is not an easy task as it is necessary to capture the complex relationship between the availability of water and the generation of electricity. This task is also more complex when performed for a large interconnected area. In this work, a model is built for several European countries by using machine learning techniques. In particular, we compare the accuracy of models based on the Random Forest algorithm and show that a more accurate model is obtained when a finer spatial resolution of climate data is introduced. We then discuss the practical applicability of a machine learning model for the medium term forecasts and show that some very context specific but influential events are hard to capture.
High-Dose Liraglutide and SGLT2 Inhibitor: A Promising Combination
Authors: Chua Marvin Wei Jie
Published: December 2021

Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists are important drugs in our armamentarium of treatment for Type 2 diabetes mellitus (DM). In addition to their glucose-lowering effects, they have effects on weight, other metabolic diseases and perhaps most importantly, a cardioprotective and reno-protective effect. Liraglutide is a long-acting GLP-1 agonist which was originally used at 1.8 mg daily for the treatment of DM. However, high-dose liraglutide—liraglutide 3 mg daily, has been demonstrated to be a safe and effective treatment for obesity, with or without DM. In this manuscript, I present two patients who had unusual responses to combination therapy with high-dose liraglutide and SGLT2 inhibitor—marked and/or rapid improvement in glycemic control and weight loss. Drawing from the observations in both cases, I discuss the complementary mechanisms of actions of both drugs, review the clinical effects of combination therapy and distil them into clinical pearls of practical utility for the physician. Given the “clash of the two pandemics” of obesity and COVID-19 and the burgeoning rates of obesity which loom in the near horizon, this is most timely.
Limited Mobility to the Bed Reduces the Chances of Discharge and Increases the Chances of Death in the ICU
Authors: dos Santos Moraes Talita Leite , de Farias Joana Monteiro Fraga , Rezende Brunielly Santana , de Carvalho Fernanda Oliveira , Santiago Michael Silveira , Porto Erick Sobral , Doria Felipe Meireles , Santana Kleberton César Siqueira , Gomes Marcel Vieira , Leite Victor Siqueira , Madruga Reuthemann Esequias Teixeira Tenório Albuquerque , dos Santos Maciel Leonardo Yung , Andrade Juliana Dantas , de Farias Neto Jader Pereira , Aidar Felipe J. , da Silva Junior Walderi Monteiro
Published: December 2021

Background: Progressive mobility in the ICU has been recommended; however, the definitions of low, moderate, and high mobility in the ICU still diverge between studies. Therefore, our objective was to classify the mobility of the sample from verticalization and active withdrawal from the bed, and from that, to analyze the chances of discharge, death, and readmission to the ICU. Materials and methods: This is an observational and retrospective study that consults the medical records of individuals admitted to the ICU of the University Hospital of Sergipe (HU/SE) between August 2017 and August 2018. Mobility level was classified based on the Intensive Care Unit Mobility Scale (IMS). Results: A total of 121 individuals were included. The mean age was 61.45 ± 16.45, being 53.7% female. Of these, 28 (23.1%) had low mobility, 33 (27.3%) had moderate mobility, and 60 (49.6%) had high mobility. Individuals with low mobility were 45 times more likely to die (OR = 45.3; 95% CI = 3.23–636.3) and 88 times less likely to be discharged from the ICU (OR = 0.22; 95% CI = 0.002–0.30). Conclusion: Those who evolved with low mobility had a higher chance of death and a lower chance of discharge from the ICU. Moderate and high mobility were not associated with the investigated outcomes.
Tribo-Behavior and Corrosion Properties of Welded 304L and 316L Stainless Steel
Authors: Abdo Hany S. , Seikh Asiful H. , Alharbi Hamad F. , Mohammed Jabair Ali , Soliman Mahmoud S. , Fouly Ahmed , Ragab Sameh A.
Published: December 2021

The present study investigates the electrochemical corrosion response and tribo-behavior of 304L and 316L stainless steel welded by gas metal arc welding (GMAW), which offered a high deposition rate. During this research, the metallurgically prepared welded samples were subjected to a tribological test and a corrosion test. The wear results were favorable for 316L steel, and it showed a lower coefficient of friction than the 304L specimen. These samples also underwent characterization studies, such as X-ray diffractometry (XRD) and scanning electron microscopy (SEM), to identify the different phases obtained on the cooling of the weld pool. Finally, both specimens were compared against their mechanical properties. Owing to the above properties, the 316L sample showed lasting durability, as compared to the 304L steel. The primary compositional difference is the higher presence of molybdenum and chromium in the 316L steel, compared to the 304L stainless steel.
Investigations of Thermal Stability and Spectroscopic Features of Sm3+ Doped Strontium Aluminate Glasses
Authors: Li Pengfei , Zhang Xiaoyan , Zhang Jinrong , Qi Xiwei , Liu Xin
Published: December 2021

In the present work, a series of Sm3+ doped transparent strontium aluminate glasses with the composition Al2O3-(3-x)SrO: xSm3+ (x = 0, 0.01, 0.03, 0.06, 0.1, 0.2) were fabricated by a containerless process using an aerodynamic levitation furnace. The structural characteristics, density, Vicker’s hardness, and thermal and spectroscopic behaviors of these glasses were investigated. All the glasses exhibit excellent thermal stabilities (Tg ≥ 792 °C) and the glass-forming ability is enhanced with the increasing content of Sm3+. The emission spectra recorded under an excitation of 404 nm show four emission transitions as a result of 4G5/2 translated to the lower states of 6H5/2, 6H7/2, 6H9/2, and 6H11/2, and a bright orange-reddish luminescence can be observed in Al2O3-(3-x)SrO: xSm3+ glasses. The high thermal stability, good glass-forming ability and excellent hardness provide new options for the development of visible orange-reddish lasers and smart photoluminescent glass coating materials.
Ag Nanoislands Modified Carbon Fiber Nanostructure: A Versatile and Ultrasensitive Surface-Enhanced Raman Scattering Platform for Antiepileptic Drug Detection
Authors: Shi Guochao , Han Xue , Gu Jungai , Yuan Wenzhi , Li Kuihua , Wang Liyong , Han Wei , Gu Jianjun
Published: December 2021

A high-efficiency surface-enhanced Raman scattering (SERS) detection method with ultra-high sensitivity has been widely applied in drug component detection to optimize the product quality verification standards. Herein, a controllable strategy of sputtering Ag nanoislands on carbon fiber (C-fiber) via magnetron sputtering technology was proposed to fabricate a versatile Ag-C-fiber SERS active substrate. A wide range of multi-level electromagnetic enhancement “hot spots” distributed on Ag-C-fiber nanostructures can efficiently amplify Raman signals and the experimental enhancement factor (EEF) value was 3.871 × 106. Furthermore, substantial “hot spots” of large-scale distribution guaranteed the superior reproducibility of Raman signal with relative standard deviation (RSD) values less than 12.97%. Limit of detection (LOD) results indicated that when crystal violet (CV) is employed as probe molecule, the LOD was located at 1 × 10−13 M. By virtue of ultra-sensitivity and good flexibility of the Ag-C-fiber nanotemplate, Raman signals of two kinds of antiepileptic drugs called levetiracetam and sodium valproate were successfully obtained using an SERS-based spectral method. The Ag-C-fiber SERS detection platform demonstrated a good linear response (R2 = 0.97486) in sensing sodium valproate concentrations in the range of 1 × 103 ng/μL−1–1 ng/μL. We believe that this reliable strategy has potential application for trace detection and rapid screening of antiepileptic drugs in the clinic.
Post-Quantum and Code-Based Cryptography—Some Prospective Research Directions
Authors: Balamurugan Chithralekha , Singh Kalpana , Ganesan Ganeshvani , Rajarajan Muttukrishnan
Published: December 2021

Cryptography has been used from time immemorial for preserving the confidentiality of data/information in storage or transit. Thus, cryptography research has also been evolving from the classical Caesar cipher to the modern cryptosystems, based on modular arithmetic to the contemporary cryptosystems based on quantum computing. The emergence of quantum computing poses a major threat to the modern cryptosystems based on modular arithmetic, whereby even the computationally hard problems which constitute the strength of the modular arithmetic ciphers could be solved in polynomial time. This threat triggered post-quantum cryptography research to design and develop post-quantum algorithms that can withstand quantum computing attacks. This paper provides an overview of the various research directions that have been explored in post-quantum cryptography and, specifically, the various code-based cryptography research dimensions that have been explored. Some potential research directions that are yet to be explored in code-based cryptography research from the perspective of codes is a key contribution of this paper.