bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Bi-Specific Immuno-Modulatory Tribodies Potentiate T Cell Activation and Increase Anti-Tumor Efficacy
Authors: Passariello Margherita , Yoshioka Asami , Takahashi Kota , Hashimoto Shu-ichi , Rapuano Lembo Rosa , Manna Lorenzo , Nakamura Koji , De Lorenzo Claudia
Published: March 2022

Cancer immunotherapy has already shown significant improvements by combining different antibodies specific for distinct immune checkpoints, such as Ipilimumab and Nivolumab. Here, we tested combinatorial treatments of immunomodulatory antibodies, previously generated in our laboratory, for their effects on hPBMC activation, either upon stimulation with SEB or in co-cultures with tumor cells by cytokine secretion assays. We found that some of them showed additive or synergistic effects, and on the basis of these observations, we constructed, for the first time, four novel bispecific tribodies (TR), made up of a Fab derived from one anti-IC mAb and two scFvs derived from another mAb targeting a different IC. All four TRs cotargeting either programmed cell death protein 1 (PD-1) and Lymphocyte Activating 3 (LAG-3) or programmed death-ligand 1 (PD-L1) and LAG-3 retained binding affinity for their targets and the antagonistic effects of their parental mAbs, but some of them also showed an increased ability to induce lymphocyte activation and increased in vitro cytotoxicity against tumor cells compared to parental antibodies used either alone or in combinatorial treatments. Furthermore, none of the tribodies showed significant increased cytotoxicity on human cardiomyocytes. Considering that the tribody format reduces production costs (as only one construct provides the inhibitory effects of two antibodies), has an intermediate molecular size (100 kDa) which is well suited for both tumor penetration and an acceptable half-life, we think that these novel immunomodulatory TRBs have the potential to become precious tools for therapeutic applications, particularly in monotherapy-resistant cancer patients.
Role of ERK Pathway in the Pathogenesis of Atopic Dermatitis and Its Potential as a Therapeutic Target
Authors: Zeze Nahoko , Kido-Nakahara Makiko , Tsuji Gaku , Maehara Eriko , Sato Yuki , Sakai Sawako , Fujishima Kei , Hashimoto-Hachiya Akiko , Furue Masutaka , Nakahara Takeshi
Published: March 2022

Atopic dermatitis (AD) is an eczematous skin disorder characterized by type 2 inflammation, barrier disruption, and intense itch. In addition to type 2 cytokines, many other cytokines, such as interferon gamma (IFN-γ), interleukin 17 (IL-17), and interleukin 22 (IL-22), play roles in the pathogenesis of AD. It has been reported that the extracellular signal-regulated kinase (ERK) is downstream of such cytokines. However, the involvement of the ERK pathway in the pathogenesis of AD has not yet been investigated. We examined the expression of p-ERK in mouse and human AD skin. We also investigated the effects of the topical application of an ERK inhibitor on the dermatitis score, transepidermal water loss (TEWL), histological change, and expression of filaggrin, using an AD-like NC/Nga murine model. The effects of an ERK inhibitor on filaggrin expression in normal human epidermal keratinocytes (NHEKs) and on chemokine production from bone marrow-derived dendritic cells (BMDCs) were also evaluated. p-ERK was highly expressed in mouse and human AD skin. Topical application of an ERK inhibitor alleviated the clinical symptoms, histological changes, TEWL, and decrease in expression of filaggrin in the AD-like NC/Nga murine model. The ERK inhibitor also restored the IL-4 induced reduction in the expression of filaggrin in NHEK, and inhibited chemokine production from BMDC induced by IL-4. These results indicate that the ERK pathway is involved in the pathogenesis of AD, and suggest that the ERK pathway has potential as a therapeutic target for AD in the future.
The Conserved and Specific Roles of the LUX ARRHYTHMO in Circadian Clock and Nodulation
Authors: Kong Yiming , Zhang Yuxue , Liu Xiu , Meng Zhe , Yu Xiaolin , Zhou Chuanen , Han Lu
Published: March 2022

LUX ARRHYTHMO (LUX) plays a key role in circadian rhythms and flowering. Here, we identified the MtLUX gene which is the putative ortholog of LUX in Medicago truncatula. The roles of MtLUX, in both the nodulation belowground and leaf movement aboveground, were investigated by characterizing a loss-of-function mtlux mutant. MtLUX was required for the control of flowering time under both long-day and short-day conditions. Further investigations showed that the early flowering in the mtlux mutant was correlated with the elevated expression level of the MtFTa1 gene but in a CO-like independent manner. MtLUX played a conserved role in the regulatory interactions with MtLHY, MtTOC1, and MtPRR genes, which is similar to those in other species. Meanwhile, the unexpected functions of MtLUX were revealed in nodule formation and nyctinastic leaf movement, probably through the indirect regulation in MtLHY. Its participation in nodulation is of interest in the context of functional conservation and the neo-functionalization of the products of LUX orthologs.
Molecular Mechanisms of Cutaneous Squamous Cell Carcinoma
Authors: Hedberg Matthew L. , Berry Corbett T. , Moshiri Ata S. , Xiang Yan , Yeh Christopher J. , Attilasoy Cem , Capell Brian C. , Seykora John T.
Published: March 2022

Non-melanoma skin cancers are cutaneous malignancies representing the most common form of cancer in the United States. They are comprised predominantly of basal cell carcinomas and squamous cell carcinomas (cSCC). The incidence of cSCC is increasing, resulting in substantial morbidity and ever higher treatment costs; currently in excess of one billion dollars, per annum. Here, we review research defining the molecular basis and development of cSCC that aims to provide new insights into pathogenesis and drive the development of novel, cost and morbidity saving therapies.
Potential Resistance of SARS-CoV-2 Main Protease (Mpro) against Protease Inhibitors: Lessons Learned from HIV-1 Protease
Authors: Mótyán János András , Mahdi Mohamed , Hoffka Gyula , Tőzsér József
Published: March 2022

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome 2 (SARS-CoV-2), has been one of the most devastating pandemics of recent times. The lack of potent novel antivirals had led to global health crises; however, emergence and approval of potent inhibitors of the viral main protease (Mpro), such as Pfizer’s newly approved nirmatrelvir, offers hope not only in the therapeutic front but also in the context of prophylaxis against the infection. By their nature, RNA viruses including human immunodeficiency virus (HIV) have inherently high mutation rates, and lessons learnt from previous and currently ongoing pandemics have taught us that these viruses can easily escape selection pressure through mutation of vital target amino acid residues in monotherapeutic settings. In this paper, we review nirmatrelvir and its binding to SARS-CoV-2 Mpro and draw a comparison to inhibitors of HIV protease that were rendered obsolete by emergence of resistance mutations, emphasizing potential pitfalls in the design of inhibitors that may be of important relevance to the long-term use of novel inhibitors against SARS-CoV-2.
Genomics and Epigenomics of Gestational Diabetes Mellitus: Understanding the Molecular Pathways of the Disease Pathogenesis
Authors: Abu Samra Nadia , Jelinek Herbert F. , Alsafar Habiba , Asghar Farah , Seoud Muhieddine , Hussein Shahad M. , Mubarak Hisham M. , Anwar Siddiq , Memon Mashal , Afify Nariman , Manzoor Ridda , Al-Homedi Zahrah , Osman Wael
Published: March 2022

One of the most common complications during pregnancy is gestational diabetes mellitus (GDM), hyperglycemia that occurs for the first time during pregnancy. The condition is multifactorial, caused by an interaction between genetic, epigenetic, and environmental factors. However, the underlying mechanisms responsible for its pathogenesis remain elusive. Moreover, in contrast to several common metabolic disorders, molecular research in GDM is lagging. It is important to recognize that GDM is still commonly diagnosed during the second trimester of pregnancy using the oral glucose tolerance test (OGGT), at a time when both a fetal and maternal pathophysiology is already present, demonstrating the increased blood glucose levels associated with exacerbated insulin resistance. Therefore, early detection of metabolic changes and associated epigenetic and genetic factors that can lead to an improved prediction of adverse pregnancy outcomes and future cardio-metabolic pathologies in GDM women and their children is imperative. Several genomic and epigenetic approaches have been used to identify the genes, genetic variants, metabolic pathways, and epigenetic modifications involved in GDM to determine its etiology. In this article, we explore these factors as well as how their functional effects may contribute to immediate and future pathologies in women with GDM and their offspring from birth to adulthood. We also discuss how these approaches contribute to the changes in different molecular pathways that contribute to the GDM pathogenesis, with a special focus on the development of insulin resistance.
Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania
Authors: Priestley Jessica R. C. , Adang Laura A. , Drewes Williams Sarah , Lichter-Konecki Uta , Menello Caitlin , Engelhardt Nicole M. , DiPerna James C. , DiBoscio Brenda , Ahrens-Nicklas Rebecca C. , Edmondson Andrew C. , Reynoso Santos Francis Jeshira , Ficicioglu Can
Published: March 2022

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It results from pathogenic variants in ABCD1, which encodes the peroxisomal very-long-chain fatty acid transporter, causing a spectrum of neurodegenerative phenotypes. The childhood cerebral form of the disease is particularly devastating. Early diagnosis and intervention improve outcomes. Because newborn screening facilitates identification of at-risk individuals during their asymptomatic period, X-ALD was added to the Pennsylvania newborn screening program in 2017. We analyzed outcomes from the first four years of X-ALD newborn screening, which employed a two-tier approach and reflexive ABCD1 sequencing. There were 51 positive screens with elevated C26:0-lysophosphatidylcholine on second-tier screening. ABCD1 sequencing identified 21 hemizygous males and 24 heterozygous females, and clinical follow up identified four patients with peroxisomal biogenesis disorders. There were two false-positive cases and one false-negative case. Three unscreened individuals, two of whom were symptomatic, were diagnosed following their young siblings’ newborn screening results. Combined with experiences from six other states, this suggests a U.S. incidence of roughly 1 in 10,500, higher than had been previously reported. Many of these infants lack a known family history of X-ALD. Together, these data highlight both the achievements and challenges of newborn screening for X-ALD.
Proteogenomics Analysis Reveals Novel Micropeptides in Primary Human Immune Cells
Authors: Subbannayya Yashwanth , Bhatta Ankit , Pinto Sneha M. , Fitzgerald Katherine A. , Kandasamy Richard K.
Published: March 2022

Short open reading frames (sORFs) encoding functional peptides have emerged as important mediators of biological processes. Recent studies indicate that sORFs of long non-coding RNAs (lncRNAs) can encode functional micropeptides regulating immunity and inflammation. However, large-scale identification of potential micropeptide-encoding sequences is a significant challenge. We present a data analysis pipeline that uses immune cell-derived mass spectrometry-based proteomic data reanalyzed using a rigorous proteogenomics-based workflow. Our analysis resulted in the identification of 2815 putative lncRNA-encoded micropeptides across three human immune cell types. Stringent score cut-off and manual verification confidently identified 185 high-confidence putative micropeptide-coding events, of which a majority have not been reported previously. Functional validation revealed the expression and localization of lnc-MKKS in both nucleus and cytoplasmic compartments. Our pilot analysis serves as a resource for future studies focusing on the role of micropeptides in immune cell response.
Lotus-Leaf-Inspired Biomimetic Coatings: Different Types, Key Properties, and Applications in Infrastructures
Authors: Collins Christopher M. , Safiuddin Md.
Published: March 2022

A universal infrastructural issue is wetting of surfaces; millions of dollars are invested annually for rehabilitation and maintenance of infrastructures including roadways and buildings to fix the damages caused by moisture and frost. The biomimicry of the lotus leaf can provide superhydrophobic surfaces that can repel water droplets, thus reducing the penetration of moisture, which is linked with many deterioration mechanisms in infrastructures, such as steel corrosion, sulfate attack, alkali-aggregate reactions, and freezing and thawing. In cold-region countries, the extent of frost damage due to freezing of moisture in many components of infrastructures will be decreased significantly if water penetration can be minimized. Consequently, it will greatly reduce the maintenance and rehabilitation costs of infrastructures. The present study was conducted to explore any attempted biomimicry of the lotus leaf to produce biomimetic coatings. It focuses on anti-wetting characteristics (e.g., superhydrophobicity, sliding angle, contact angle), self-cleaning capability, durability, and some special properties (e.g., light absorbance and transmission, anti-icing capacity, anti-fouling ability) of lotus-leaf-inspired biomimetic coatings. This study also highlights the potential applications of such coatings, particularly in infrastructures. The most abundant research across coating materials showed superhydrophobicity as being well-tested while self-cleaning capacity and durability remain among the properties that require further research with existing promise. In addition, the special properties of many coating materials should be validated before practical applications.
The Effect of Wind Speed on Male Potato Aphid, Macrosiphum euphorbiae, Responses to Primary Host Plant Volatiles and Female Sex Pheromone
Authors: Alexander W. Marie , Rubin Benjamin D. , McNeil Jeremy N.
Published: March 2022

In fall, alate males of the potato aphid, Macrosiphum euphorbiae (Thomas), migrate from their summer (secondary) host plants, such as potatoes, to primary host plants, such as roses, where they mate with wingless oviparae who produce the overwintering egg stage. Males are weak fliers and generally walk towards a pheromone source under windy conditions, so we tested the hypothesis that upwind walking behaviour in response to wind velocity would be affected by the volatile cues present. We compared male responses to the odour of a rugosa rose cutting alone and to the combination of host plant volatiles and the female sex pheromone under a range of wind speeds in a laboratory walking bioassay. The proportion of males responding decreased as the wind speed increased, but at all wind velocities, the responses to the combined odours were higher than to the host plant alone. However, at any given wind velocity, the speed at which responding aphids moved was not influenced by the odour source. These findings support the idea that host plant volatiles serve as long-distance cues for males and that the female sex pheromone is used once on the host plant.
Miniature Inverted-Repeat Transposable Elements (MITEs) in the Two Lepidopteran Genomes of Helicoverpa armigera and Helicoverpa zea
Authors: Klai Khouloud , Zidi Marwa , Chénais Benoît , Denis Françoise , Caruso Aurore , Casse Nathalie , Mezghani Khemakhem Maha
Published: March 2022

Miniature inverted-repeat transposable elements MITEs are ubiquitous, non-autonomous class II transposable elements. The moths, Helicoverpa armigera and Helicoverpa zea, are recognized as the two most serious pest species within the genus. Moreover, these pests have the ability to develop insecticide resistance. In the present study, we conducted a genome-wide analysis of MITEs present in H. armigera and H. zea genomes using the bioinformatics tool, MITE tracker. Overall, 3570 and 7405 MITE sequences were identified in H. armigera and H. zea genomes, respectively. Comparative analysis of identified MITE sequences in the two genomes led to the identification of 18 families, comprising 140 MITE members in H. armigera and 161 MITE members in H. zea. Based on target site duplication (TSD) sequences, the identified families were classified into three superfamilies (PIF/harbinger, Tc1/mariner and CACTA). Copy numbers varied from 6 to 469 for each MITE family. Finally, the analysis of MITE insertion sites in defensome genes showed intronic insertions of 11 MITEs in the cytochrome P450, ATP-binding cassette transporter (ABC) and esterase genes in H. armigera whereas for H. zea, only one MITE was retrieved in the ABC-C2 gene. These insertions could thus be involved in the insecticide resistance observed in these pests.
Slow-Pathway Visualization by Using Panoramic View: A Novel Ablation Technique for Ablation of Atrioventricular Nodal Reentrant Tachycardia
Authors: Ding Lei , Weng Sixian , Zhang Hongda , Yu Fengyuan , Qi Yingjie , Zhang Shu , Tang Min
Published: March 2022

(1) Background: The panoramic view of a novel wide-band dielectric mapping system could show the individual anatomy. We aimed to compare the feasibility, efficacy and safety of the panoramic view guided approach for ablation of AVNRT with the conventional approach. (2) Methods: Ablation distributions in eight patients were retrospectively analyzed using the panoramic view. The para-slow-pathway (para-SP) region was divided into three regions, and the region that most frequently appeared with the appropriate junctional rhythm or eliminated the slow-pathway was defined as the adaptive slow-pathway (aSP) region. Twenty patients with AVNRT were then ablated in the aSP region under the panoramic view and compared with 40 patients using the conventional approach. (3) Results: Thirty ablation points were analyzed. The majority of effective points (95.0%) were located in the inferior and anterior portions of the para-SP region and defined as the aSP region. Baseline characteristics, fluoroscopic duration, and mean number of ablations were similar among the two groups. The panoramic view group had a significantly higher percentage of appropriate junctional rhythm (81.9% ± 26.0% vs. 55.7% ± 30.5%, p = 0.002) than the conventional group. (4) Conclusions: The use of the panoramic view for AVNRT ablation achieved similar clinical endpoints with higher ablation efficiency than the conventional approach.
The Risk of Bleeding and Adverse Events with Clopidogrel in Elective Hip and Knee Arthroplasty Patients
Authors: Wu Cheng-Ta , Lien Tzu-Hsien , Chen I-Ling , Wang Jun-Wen , Ko Jih-Yang , Lee Mel S.
Published: March 2022

Orthopedic surgeons often face a clinical dilemma on how to manage antiplatelet therapies during the time of surgery. This retrospective study is aimed to investigate the bleeding risk and adverse events in patients who hold or keep clopidogrel during elective major joints arthroplasty. Two hundred and ninety-six patients that were treated with clopidogrel while undergoing total hip or knee joint replacement between January 2009 and December 2018 were studied. Group 1 included 56 patients (18.9%) who kept using clopidogrel preoperatively. Group 2 included 240 patients who hold clopidogrel use ≥5 days preoperatively. Blood transfusion rates, estimated blood loss, complication rates, and adverse cardiocerebral events were collected and analyzed. The mean total blood loss was more in the group 1 patients as compared with that in the group 2 patients (1212.3 mL (685.8 to 2811.8) vs. 1068.9 mL (495.6 to 3294.3), p = 0.03). However, there was no significant difference between the two groups of patients regarding transfusion rates, bleeding-related complications, and infection rates. There was a trend toward a higher incidence of adverse cardiocerebral events in patients withholding clopidogrel for more than 5 days before surgery. The results of this study suggest that clopidogrel continuation could be safe and advisable for patients at thrombotic risk undergoing primary major joint replacement. Acute antiplatelet withdrawal for an extended period of time might be associated with an increased risk of postoperative thromboembolic events. More studies are required in the future to further prove this suggestion.
Improvement of Type 2 Diabetes Mellitus and Attenuation of NAFLD Are Associated with the Success of Obesity Therapy
Authors: Schmid Andreas , Arians Miriam , Karrasch Thomas , Pons-Kühnemann Jörn , Schäffler Andreas , Roderfeld Martin , Roeb Elke
Published: March 2022

Obesity and type 2 diabetes mellitus (T2D) represent important comorbidities of the metabolic syndrome, which are associated with non-alcoholic fatty liver disease (NAFLD)-related hepatic fibrosis. In total, 160 morbidly obese patients—81 following a low-calorie formula diet (LCD) program and 79 undergoing bariatric surgery (Roux-en-Y gastric bypass, RYGB)—were examined for anthropometric and metabolic parameters at base-line and during 12 months of weight loss, focusing on a putative co-regulation of T2D parameters and liver fibrosis risk. High NAFLD fibrosis scores (NFS) before intervention were associated with elevated HbA1c levels and T2D. Loss of weight and body fat percentage (BFL) were associated with improved glucose and lipid metabolism and reduced risk of NAFLD-related fibrosis, with particularly beneficial effects by RYGB. Both T2D improvement and NFS decrease were positively associated with high BFL. A highly significant correlation of NFS reduction with BFL was restricted to male patients while being absent in females, accompanied by generally higher BFL in men. Overall, the data display the relation of BFL, T2D improvement, and reduced NAFLD-related fibrosis risk during weight loss in morbidly obese individuals induced by diet or RYGB. Furthermore, our data suggest a considerable sexual dimorphism concerning the correlation of fat loss and improved risk of liver fibrosis.
Comparison of LC-MS and LC-DAD Methods of Detecting Abused Piperazine Designer Drugs
Authors: Welz Anna , Koba Marcin , Kośliński Piotr , Siódmiak Joanna
Published: March 2022

Recreational use of piperazine designer drugs is a serious threat to human health. These compounds act on the body in a similar fashion to illegal drugs. They induce psychostimulatory effects as well as visual and auditory hallucinations to varying degrees. In many cases of poisoning and deaths, the presence of two or even several psychoactive substances have been demonstrated. Piperazine derivatives are often found in such mixtures and pose a great analytical problem during their identification. Additionally, some piperazine derivatives can be detected in biological material as a result of metabolic changes to related drugs. Therefore, it is necessary to correctly identify these compounds and ensure repeatability of determinations. This article presents a comparison of the methods used to detect abused piperazine designer drugs using liquid chromatography in combination with a diode-array detector (LC-DAD) or mass spectrometer (LC-MS). Each of methods can be used independently for determinations, obtaining reliable results in a short time of analysis. These methods can also complement each other, providing qualitative and quantitative confirmation of results. The proposed methods provide analytical confirmation of poisoning and may be helpful in toxicological diagnostics.
Expression of Calbindin, a Marker of Gamma-Aminobutyric Acid Neurons, Is Reduced in the Amygdala of Oestrogen Receptor β-Deficient Female Mice
Authors: Kalinowski Daniel , Bogus-Nowakowska Krystyna , Kozłowska Anna , Równiak Maciej
Published: March 2022

Oestrogen receptor β (ERβ) knock-out female mice display increased anxiety and decreased threshold for synaptic plasticity induction in the basolateral amygdala. This may suggest that the γ-aminobutyric acid (GABA) inhibitory system is altered. Therefore, the immunoreactivity of main GABAergic markers—i.e., calbindin, parvalbumin, calretinin, somatostatin, α1 subunit-containing GABAA receptor and vesicular GABA transporter—were compared in the six subregions (LA, BL, BM, ME, CE and CO) of the amygdala of adult female wild-type and ERβ knock-out mice using immunohistochemistry and quantitative methods. The influence of ERβ knock-out on neuronal loss and glia was also elucidated using pan-neuronal and astrocyte markers. The results show severe neuronal deficits in all main amygdala regions in ERβ knock-out mice accompanied by astroglia overexpression only in the medial, basomedial and cortical nuclei and a decrease in calbindin-expressing neurons (CB+) in the amygdala in ERβ knock-out mice compared with controls, while other markers of the GABAergic system remain unchanged. Concluding, the lack of ERβ led to failure in the structural integrity of the CB+ subpopulation, reducing interneuron firing and resulting in a disinhibitory effect over pyramidal function. This fear-promoting excitatory/inhibitory alteration may lead to the increased anxiety observed in these mice. The impact of neuronal deficits and astroglia overexpression on the amygdala functions remains unknown.
Hearing Therapy Improves Tinnitus-Related Distress in Mildly Distressed Patients with Chronic Tinnitus and Mild-to-Moderate Hearing Loss: A Randomized-Controlled Cross-Over Design
Authors: Boecking Benjamin , Rausch Leonie , Psatha Stamatina , Nyamaa Amarjargal , Dettling-Papargyris Juliane , Funk Christine , Brueggemann Petra , Rose Matthias , Mazurek Birgit
Published: March 2022

Background: The psychological effects of hearing aids and auditory training are underinvestigated. Objective: To assess the short- and long-term effects of an industry-developed auditory training on tinnitus-related distress, perceived stress, and psychological epiphenomena in patients with chronic tinnitus and mild-to-moderate hearing loss. Method: One-hundred-seventy-seven gender-stratified patients were randomized to an immediate [IIG] or delayed [DIG] intervention group. Following binaural hearing aid fitting, participants completed a CD-enhanced 14-days self-study program. Applying a randomized-controlled cross-over design, psychological measures were obtained at four times: pre-treatment/wait [IIG: t1; DIG: wait], post-treatment/pre-treatment [IIG: t2; DIG: t1], follow-up/post-treatment [IIG: t3; DIG: t2], and follow-up [DIG: t3]. Between- and within-group analyses investigated treatment-related effects and their stability at a 70-day follow-up. Results: Overall, distress symptom severity was mild. Unlike the DIG, the IIG showed significant improvements in tinnitus-related distress. Some psychological epiphenomena, notably anxiety, slightly improved in both groups. Within-group analyses demonstrated the stability of the tinnitus-distress-related effects, alongside uncontrolled improvements of perceived stress and mood-related symptoms at follow-up. Conclusions: The investigated hearing therapy lastingly improves tinnitus-related distress in mildly distressed patients with chronic tinnitus and mild-to-moderate hearing loss. Beneficial psychological knock-on effects deserve further investigation.
Does the Serum Concentration of Angiotensin II Type 1 Receptor Have an Effect on the Severity of COVID-19? A Prospective Preliminary Observational Study among Healthcare Professionals
Authors: Janc Jarosław , Suchański Michał , Mierzchała-Pasierb Magdalena , Woźnica-Niesobska Ewa , Łysenko Lidia , Leśnik Patrycja
Published: March 2022

SARS-CoV-2 is a virus that causes severe respiratory distress syndrome. The pathophysiology of COVID-19 is related to the renin–angiotensin system (RAS). SARS-CoV-2, a vector of COVID-19, uses angiotensin-converting enzyme 2 (ACE-2), which is highly expressed in human lung tissue, nasal cavity, and oral mucosa, to gain access into human cells. After entering the cell, SARS-CoV-2 inhibits ACE-2, thus favouring the ACE/Ang II/angiotensin II type 1 receptor (AT1R) axis, which plays a role in the development of acute lung injury (ALI). This study aimed to analyse the influence of angiotensin 1 receptor (AT1R) levels in the serum on the course of the severity of symptoms in healthcare professionals who had a SARS-CoV-2 infection. This prospective observational study was conducted on a group of 82 participants. The study group included physicians and nurses who had a COVID-19 infection confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2. The control group consisted of healthy medical professionals who had not had a SARS-CoV-2 infection or who had no symptoms of COVID-19 and who tested negative for SARS-CoV-2 on the day of examination. We analysed the correlation between AT1R concentration and the severity of COVID-19, as well as with sex, age, blood group, and comorbidities. There were no statistically significant differences in the mean values of AT1R concentration in the recovered individuals and the non-COVID-19 subjects (3.29 vs. 3.76 ng/mL; p = 0.32). The ROC curve for the AT1R assay showed an optimal cut-off point of 1.33 (AUC = 0.44; 95% CI = 0.32–0.57; p = 0.37). There was also no correlation between AT1R concentration and the severity of symptoms associated with COVID-19. Blood type analysis showed statistically significantly lower levels of AT1R in COVID-19-recovered participants with blood group A than in those with blood group O. In conclusion, AT1R concentration does not affect the severity of symptoms associated with COVID-19 among healthcare professionals.
PEEK Biomaterial in Long-Term Provisional Implant Restorations: A Review
Authors: Suphangul Suphachai , Rokaya Dinesh , Kanchanasobhana Chatruethai , Rungsiyakull Pimduen , Chaijareenont Pisaisit
Published: March 2022

Polyetheretherketone (PEEK) has become a useful polymeric biomaterial due to its superior properties and has been increasingly used in dentistry, especially in prosthetic dentistry and dental implantology. Promising applications of PEEK in dentistry are dental implants, temporary abutment, implant-supported provisional crowns, fixed prosthesis, removable denture framework, and finger prosthesis. PEEK as a long-term provisional implant restoration has not been studied much. Hence, this review article aims to review PEEK as a long-term provisional implant restoration for applications focusing on implant dentistry. Articles published in English on PEEK biomaterial for long-term provisional implant restoration were searched in Google Scholar, ScienceDirect, PubMed/MEDLINE, and Scopus. Then, relevant articles were selected and included in this literature review. PEEK presents suitable properties for various implant components in implant dentistry, including temporary and long-term provisional restorations. The modifications of PEEK result in wider applications in clinical dentistry. The PEEK reinforced by 30–50% carbon fibers can be a suitable material for the various implant components in dentistry.
Addressing Motion Blurs in Brain MRI Scans Using Conditional Adversarial Networks and Simulated Curvilinear Motions
Authors: Li Shangjin , Zhao Yijun
Published: March 2022

In-scanner head motion often leads to degradation in MRI scans and is a major source of error in diagnosing brain abnormalities. Researchers have explored various approaches, including blind and nonblind deconvolutions, to correct the motion artifacts in MRI scans. Inspired by the recent success of deep learning models in medical image analysis, we investigate the efficacy of employing generative adversarial networks (GANs) to address motion blurs in brain MRI scans. We cast the problem as a blind deconvolution task where a neural network is trained to guess a blurring kernel that produced the observed corruption. Specifically, our study explores a new approach under the sparse coding paradigm where every ground truth corrupting kernel is assumed to be a “combination” of a relatively small universe of “basis” kernels. This assumption is based on the intuition that, on small distance scales, patients’ moves follow simple curves and that complex motions can be obtained by combining a number of simple ones. We show that, with a suitably dense basis, a neural network can effectively guess the degrading kernel and reverse some of the damage in the motion-affected real-world scans. To this end, we generated 10,000 continuous and curvilinear kernels in random positions and directions that are likely to uniformly populate the space of corrupting kernels in real-world scans. We further generated a large dataset of 225,000 pairs of sharp and blurred MR images to facilitate training effective deep learning models. Our experimental results demonstrate the viability of the proposed approach evaluated using synthetic and real-world MRI scans. Our study further suggests there is merit in exploring separate models for the sagittal, axial, and coronal planes.
Concept and Performance Analysis of Propulsion Units Intended for Distributed Ship Systems
Authors: Illes Ladislav , Jurkovic Martin , Kalina Tomas , Sosedova Jarmila , Gorzelanczyk Piotr , Stopka Ondrej , Kubjatko Tibor
Published: March 2022

Limited navigation depth, especially on inland waterways, is one of the main limiting factors that shorten the navigation period. Distributed propulsion systems represent an opportunity to increase the navigability of ships across critical sections of waterways characterized by limited navigation depth. In the case of distributed propulsion systems, it is necessary to examine the position of the propellers and their efficiency, suitable design, and interaction with the surroundings. In this study, self-propelled propulsion units located on the side of the ship are investigated at the level of computational fluid dynamics (CFD) analyses. Seven different types of ducts are considered for the proposed propeller geometry in order to ensure the necessary water supply, to prevent air intake, and to ensure high performance in the serial arrangement of propulsors on the side of the hull. Comparative analyses have shown that propulsion units with Ducts 5 and 6 have sufficient resistance to ventilation at a limited depth and deliver acceptable performance at low inflow and outflow rates. This feature is important in serial configurations, which confirms previous research on this issue. Performance can be further increased by reducing the duct resistance at higher speeds.
Optimizing Source Wavelets Extracted from the Chirp Sub-Bottom Profiler Using an Adaptive Filter with Machine Learning
Authors: Kim Sung-Bo , Park Hong-Lyun
Published: March 2022

In this study, we extracted three source wavelets of a Chirp sub-bottom profiler (SBP), which is widely used for high-resolution marine seismic exploration, using a MATLAB-based graphical user interface tool for computational processing. To extract the source wavelet for general seismic exploration data processing techniques, including that for Chirp SBPs, we first evaluated source wavelet extraction techniques using an adaptive machine learning filter. Subsequently, we performed deterministic deconvolution by extracting the optimal source wavelet from the raw data of Chirp SBP. This source wavelet was generated by applying an adaptive filter. Various methods have been studied to solve the multivariate optimization problem of minimizing the error; in this study, a least-mean-square algorithm was selected owing to its suitability for application to geophysical time-series data. Extracting the source wavelet is a crucial part of high-resolution marine seismic wave exploration data processing. Our results highlight the effectiveness of performing deterministic deconvolution by extracting source wavelets using adaptive filters, and we believe that our method is useful for marine seismic exploration data processing.
Genome-Wide Analysis of Cytochrome P450s of Alternaria Species: Evolutionary Origin, Family Expansion and Putative Functions
Authors: Dauda Wadzani Palnam , Morumda Daji , Abraham Peter , Adetunji Charles Oluwaseun , Ghazanfar Shakira , Glen Elkanah , Abraham Shittu Emmanuel , Peter Grace Wabba , Ogra Israel Ogwuche , Ifeanyi Ulasi Joseph , Musa Hannatu , Azameti Mawuli Kwamla , Paray Bilal Ahamad , Gulnaz Aneela
Published: March 2022

Cytochrome P450s are a group of monooxygenase enzymes involved in primary, secondary and xenobiotic metabolisms. They have a wide application in the agriculture sector where they could serve as a target for herbicides or fungicides, while they could function in the pharmaceutical industry as drugs or drugs structures or for bioconversions. Alternaria species are among the most commonly encountered fungal genera, with most of them living as saprophytes in different habitats, while others are parasites of plants and animals. This study was conducted to elucidate the diversity and abundance, evolutionary relationships and cellular localization of 372 cytochrome P450 in 13 Alternaria species. The 372 CYP proteins were phylogenetically clustered into ten clades. Forty (40) clans and seventy-one (71) cyp families were identified, of which eleven (11) families were found to appear in one species each. The majority of the CYP proteins were located in the endomembrane system. Polyketide synthase (PKS) gene cluster was the predominant secondary metabolic-related gene cluster in all the Alternaria species studied, except in A. porriof, where non-ribosomal peptide synthetase genes were dominant. This study reveals the expansion of cyps in these fungal genera, evident in the family and clan expansions, which is usually associated with the evolution of fungal characteristics, especially their lifestyle either as parasites or saprophytes, with the ability to metabolize a wide spectrum of substrates. This study can be used to understand the biology, physiology and toxigenic potentials of P450 in these fungal genera.
Antimicrobial Volatiles of the Insect Pathogen Metarhizium brunneum
Authors: Hummadi Esam Hamid , Cetin Yarkin , Demirbek Merve , Kardar Nadeems M. , Khan Shazia , Coates Christopher J. , Eastwood Daniel C. , Dudley Ed , Maffeis Thierry , Loveridge Joel , Butt Tariq M.
Published: March 2022

Fungal volatile organic compounds (VOCs) represent promising candidates for biopesticide fumigants to control crop pests and pathogens. Herein, VOCs produced using three strains of the entomopathogenic fungus Metarhizium brunneum were identified via GC-MS and screened for antimicrobial activity. The VOC profiles varied with fungal strain, development state (mycelium, spores) and culture conditions. Selected VOCs were screened against a range of rhizosphere and non-rhizosphere microbes, including three Gram-negative bacteria (Escherichia coli, Pantoea agglomerans, Pseudomonas aeruginosa), five Gram-positive bacteria (Micrococcus luteus, Staphylococcus aureus, Bacillus subtilis, B. megaterium, B. thuringiensis), two yeasts (Candida albicans, Candida glabrata) and three plant pathogenic fungi (Pythium ultimum, Botrytis cinerea, Fusarium graminearum). Microbes differed in their sensitivity to the test compounds, with 1-octen-3-ol and isovaleric acid showing broad-spectrum antimicrobial activity. Yeasts and bacteria were inhibited by the same VOCs. Cryo-SEM showed that both yeasts and bacteria underwent some form of “autolysis”, where all components of the cell, including the cell wall, disintegrated with little evidence of their presence in the clear, inhibition zone. The oomycete (P. ultimum) and ascomycete fungi (F. graminearum, B. cinerea) were sensitive to a wider range of VOCs than the bacteria, suggesting that eukaryotic microbes are the main competitors to M. brunneum in the rhizosphere. The ability to alter the VOC profile in response to nutritional cues may assist M. brunneum to survive among the roots of a wide range of plant species. Our VOC studies provided new insights as to how M. brunneum may protect plants from pathogenic microbes and correspondingly promote healthy growth.
Adherence to Therapy in Glaucoma Treatment—A Review
Authors: Zaharia Alexandra-Cătălina , Dumitrescu Otilia-Maria , Radu Mădălina , Rogoz Roxana-Elena
Published: March 2022

Glaucoma is a chronic disease and the second leading cause of irreversible vision loss worldwide, whose initial treatment consists of self-administered topical ocular hypotensive eyedrops. Adherence with glaucoma medications is a fundamental problem in the care of glaucoma patients as up to 50% of patients fail to receive the intended benefits of the treatment. The literature has identified many barriers to patients’ compliance, from factors depending on the type of medication administered, communication between physician and patients, to factors dependent on patients’ behaviour and lifestyle. Failure to take medication as prescribed increases the risk that patients will not receive the desired benefit, which often leads to a worsening of the disease. Our aim is to synthesize the methods used for measuring adherence of patients to glaucoma therapy and the interventions used for addressing adherence, laying emphasis on a patient-centred approach, taking time to educate patients about their chronic disease and to assess their views on treatment.
The Effectiveness of Predicting Suicidal Ideation through Depressive Symptoms and Social Isolation Using Machine Learning Techniques
Authors: Kim Sunhae , Lee Kounseok
Published: March 2022

(1) Background: Social isolation is a major risk factor for suicidal ideation. In this study, we investigated whether the evaluation of both depression and social isolation in combination could effectively predict suicidal ideation; (2) Methods: A total of 7994 data collected from community residents were analyzed. Statistical analysis was performed using age, the Patient Health Questionnaire-9, and the Lubben Social Network Scale as predictors as the dependent variables for suicidal ideation; machine learning (ML) methods K-Nearest Neighbors, Random Forest, and Neural Network Classification were used; (3) Results: The prediction of suicidal ideation using depression and social isolation showed high area under the curve (0.643–0.836) and specificity (0.959–0.987) in all ML techniques. In the predictor model (model 2) that additionally evaluated social isolation, the validation accuracy consistently increased compared to the depression-only model (model 1); (4) Conclusions: It is confirmed that the machine learning technique using depression and social isolation can be an effective method when predicting suicidal ideation.
Quantitative Evaluation of Urban Style at Street Level: A Case Study of Hengyang County, China
Authors: Zheng Bohong , Guo Rui , Bedra Komi Bernard , Xiang Yanfen
Published: March 2022

Urban style is the comprehensive expression of the material environment, the associated cultural connotation and social life. Under the influence of globalization and rapid urban expansion, many cities around the world show a global convergence in style, which poses a challenge in terms of satisfying both function and local identity. However, the current insufficiency of research on the quantitative evaluation of urban style makes it hard to have a full grasp on how urban style can instruct land use and landscape planning strategies. In this paper, we propose Suitability, Aesthetics and Vitality as three core dimensions of urban style, and construct a quantitative evaluation framework for urban style evaluation at the street level. Taking a street in Hengyang County, China as an example, the method’s operability is demonstrated, and the results show that urban style performance is closely related to building construction periods, trends of urban expansion, and the natural environment. Improvement strategies include harmonizing urban spatial form, increasing the diversity of land use, and moderately improving the quality of building facades. This method can be applied at a greater scale to effectively reflect local characteristics and relevant problems. It can also provide an objective basis for future planning and construction.
Developing a Technology-Based Classroom Assessment of Academic Reading Skills for English Language Learners and Teachers: Validity Evidence for Formative Use
Authors: Wolf Mikyung Kim , Lopez Alexis A.
Published: March 2022

In U.S. K-12 schools, adequate education of English language learner (EL) students, particularly to support their attainment of English language and literacy skills, has attracted heightened attention. The increased academic rigor as well as sophisticated disciplinary language demands embodied in current academic content standards have posed considerable challenges to EL students. To address students’ needs, the present study utilized formative assessment as a means to support the teaching and learning of academic reading skills for EL students. We also endeavored to test our underlying assumption that sound assessment tools would facilitate effective formative assessment processes. In this study, we devised a technology-based assessment tool considering the increasing use of technology in K-12 schools. As a small-scale, exploratory study, we examined the usability and validity of the tool for formative purposes with three ESL teachers and their students (62 EL students) from secondary schools. The results indicated that the tool had the potential to extend teachers’ and students’ formative assessment practices in principled ways. However, we also found some teachers’ misconceptions about the tool’s purpose and their limited implementation skills to utilize the tool for formative assessment purposes. Implications for practice and further research are discussed.
Multiobjective Location Problems with Variable Domination Structures and an Application to Select a New Hub Airport
Authors: Zargini Bettina
Published: March 2022

Background: Nowadays, variable domination structure is instrumental in studying multiobjective decision making problems. We investigate multiobjective location problems with respect to variable domination structure and its applications in supply chain management. Methods: We formulate practical problems in supply chain management as an optimization problem with a variable domination structure. Moreover, we present the mathematical methods to solve such problems. We investigate two kinds of solutions derived from the concept of minimal and nondominated solutions from vector optimization problems with respect to variable domination structure. Furthermore, we explore how these solution concepts are characterized in practical problems. Results: We ex- pose how those solutions are beneficial in practical problems. However, these results hold true for multiobjective decision making problems with a continuous feasible set; we present a practical problem in the case of a finite set of feasible locations. Conclusions: In many multiobjective location problems, each location’s characterizations, preferences, and restrictions are involved in the decision making process. This study investigates the decision making problems, where different preferences of objective functions at each location are assumed. Moreover, we present a numerical experiment for selecting a new hub airport.