bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the Mobilization of an Unsaturated Infinite Natural Slope Due to Strength Reduction
Authors: Navarro Vicente , De la Morena Gema , Torres-Serra Joel , Ruiz Emilio , Asensio Laura
Published: November 2022

This work analyses the mobilization of infinite natural slopes that are initially partially saturated. Starting from dry conditions (the water table is assumed to be deep, far from the slope surface), the soil shear strength will decrease when the wetting front advances from the surface. First, the geometry of the failure mechanism that can develop because of such strength reduction is determined. Second, after the mobilization causes the progressive reduction in the soil strength, the slide speed reached the minimum strength is determined, obtaining an indicator of the risk derived from failure.
A Pilot Feasibility Study to Establish Full Pulpotomy in Mature Permanent Teeth with Symptomatic Irreversible Pulpitis as a Routine Treatment in Mexican Public Healthcare Services
Authors: Sánchez-Lara y Tajonar Roberto Gustavo , Vergara-Tinoco Jaime Vicente , Dammaschke Till , Domínguez-Pérez Rubén Abraham
Published: November 2022

Symptomatic irreversible pulpitis is a common dental disease for which root canal treatment (RCT) has been the standard treatment. However, in many countries, RCT is considered a high-cost treatment that is not covered by public healthcare services; this forces patients to have dental extraction as their only option to relieve pain. In the last decade, several investigations have provided evidence that an alternative treatment known as full pulpotomy (FP) could be an alternative for patients who could not afford the cost of an RCT. Nevertheless, evidence is lacking on the success rate that could be obtained if it is performed in a public dental care clinic (PDCC). The present investigation has two main objectives. To be the first approach of a multicentric feasibility study to find out whether an FP performed by a general practice dentist (GPD) in a PDCC could be suitable and establish its success rate and patient satisfaction. Patients attending a PDCC with symptoms of irreversible pulpitis were invited to participate. FP was performed and followed up at 1, 3, 6, 9, and 12 months. The treatment success was assessed by combining three variables, patient satisfaction, clinical, and radiographic outcomes. Forty-one patients from 17 to 78 years old received the intervention. In total, 97.5% were completely satisfied with the treatment and were considered successful since none of the clinical or radiographic variables were present in any of the follow-ups. An FP performed by a GPD in a PDCC could be suitable as a routine treatment for symptomatic irreversible pulpitis due to the excellent success rate and patient satisfaction.
Structural and Biophysical Characterization of Stable Alpha-Synuclein Oligomers
Authors: Vaikath Nishant , Sudhakaran Indulekha , Abdi Ilham , Gupta Vijay , Majbour Nour , Ghanem Simona , Abdesselem Houari , Vekrellis Kostas , El-Agnaf Omar
Published: November 2022

The aggregation of α-synuclein (α-syn) into neurotoxic oligomers and fibrils is an important pathogenic feature of synucleinopatheis, including Parkinson’s disease (PD). A further characteristic of PD is the oxidative stress that results in the formation of aldehydes by lipid peroxidation. It has been reported that the brains of deceased patients with PD contain high levels of protein oligomers that are cross-linked to these aldehydes. Increasing evidence also suggests that prefibrillar oligomeric species are more toxic than the mature amyloid fibrils. However, due to the heterogenous and metastable nature, characterization of the α-syn oligomeric species has been challenging. Here, we generated and characterized distinct α-syn oligomers in vitro in the presence of DA and lipid peroxidation products 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE). HNE and ONE oligomer were stable towards the treatment with SDS, urea, and temperature. The secondary structure analysis revealed that only HNE and ONE oligomers contain β-sheet content. In the seeding assay, both DA and ONE oligomers significantly accelerated the aggregation. Furthermore, all oligomeric preparations were found to seed the aggregation of α-syn monomers in vitro and found to be cytotoxic when added to SH-SY5Y cells. Finally, both HNE and ONE α-syn oligomers can be used as a calibrator in an α-syn oligomers-specific ELISA.
Methylone and MDMA Pharmacokinetics Following Controlled Administration in Humans
Authors: Poyatos Lourdes , Lo Faro Alfredo Fabrizio , Berardinelli Diletta , Sprega Giorgia , Malaca Sara , Pichini Simona , Huestis Marilyn A. , Papaseit Esther , Pérez-Mañá Clara , Busardò Francesco Paolo , Farré Magí
Published: November 2022

The aim of this study is to define, for the first time, human methylone and HMMC plasma pharmacokinetics following controlled administration of 50–200 mg methylone to 12 male volunteers. A new LC-MS/MS method was validated to quantify methylone, MDMA, and their metabolites in plasma. The study was a randomized, cross-over, double-blinded and placebo-controlled study, with a total of 468 plasma samples collected. First, 10 µL of MDMA-d5, MDA-d5 and methylone-d3 internal standards were added to 100 µL of plasma. Two mL of chloroform and ethyl acetate 9:1 (v/v) were then added, mixed well and centrifuged. The supernatant was fortified with 0.1 mL acidified methanol and evaporated under nitrogen. Samples were reconstituted with a mobile phase and injected into the LC-MS/MS instrument. The method was fully validated according to OSAC guidelines (USA). Methylone plasma concentrations increased in a dose-proportional manner, as demonstrated by the increasing maximum concentration (Cmax) and area under the curve of concentrations (AUC). Methylone Cmax values were reported as 153, 304, 355 and 604 ng/mL, AUC0–24 values were reported as 1042.8, 2441.2, 3524.4 and 5067.9 h·ng/mL and T1/2 values as 5.8, 6.4, 6.9 and 6.4 h following the 50, 100, 150 and 200 mg doses, respectively. Methylone exhibited rapid kinetics with a Tmax of 1.5 h for the 50 mg dose and 2 h approximately after all the other doses. HMMC exhibited faster kinetics compared to methylone, with a Cmax value that was 10–14-fold lower and an AUC0–24 value that was 21–29-fold lower. Methylone pharmacokinetics was linear across 50–200 mg oral doses in humans, unlike the previously described non-linear oral MDMA pharmacokinetics. An LC-MS/MS method for the quantification of methylone, MDMA and their metabolites in human plasma was achieved. Methylone exhibited linear pharmacokinetics in humans with oral doses of 50–200 mg.
Na+/K+- and Mg2+-ATPases and Their Interaction with AMPA, NMDA and D2 Dopamine Receptors in an Animal Model of Febrile Seizures
Authors: Crespo María , León-Navarro David Agustín , Martín Mairena
Published: November 2022

Febrile seizures (FS) are one of the most common seizure disorders in childhood which are classified into short and prolonged, depending on their duration. Short FS are usually considered as benign. However, epidemiological studies have shown an association between prolonged FS and temporal lobe epilepsy. The development of animal models of FS has been very useful to investigate the mechanisms and the consequences of FS. One of the most used, the “hair dryer model”, has revealed that prolonged FS may lead to temporal lobe epilepsy by altering neuronal function. Several pieces of evidence suggest that Na+/ K+-ATPase and Mg2+-ATPase may play a role in this epileptogenic process. In this work, we found that hyperthermia-induced seizures (HIS) significantly increased the activity of Na+/ K+-ATPase and Mg2+-ATPase five and twenty days after hyperthermic insult, respectively. These effects were diminished in response to AMPA, D2 dopamine A1 and A2A receptors activation, respectively. Furthermore, HIS also significantly increased the protein level of the AMPA subunit GluR1. Altogether, the increased Na+/ K+-ATPase and Mg2+-ATPase agree well with the presence of protective mechanisms. However, the reduction in ATPase activities in the presence of NMDA and AMPA suggest an increased propensity for epileptic events in adults.
The Innate Immune System in Cardiovascular Diseases and Its Role in Doxorubicin-Induced Cardiotoxicity
Authors: Bhagat Anchit , Shrestha Pradeep , Kleinerman Eugenie S.
Published: November 2022

Innate immune cells are the early responders to infection and tissue damage. They play a critical role in the initiation and resolution of inflammation in response to insult as well as tissue repair. Following ischemic or non-ischemic cardiac injury, a strong inflammatory response plays a critical role in the removal of cell debris and tissue remodeling. However, persistent inflammation could be detrimental to the heart. Studies suggest that cardiac inflammation and tissue repair needs to be tightly regulated such that the timely resolution of the inflammation may prevent adverse cardiac damage. This involves the recognition of damage; activation and release of soluble mediators such as cytokines, chemokines, and proteases; and immune cells such as monocytes, macrophages, and neutrophils. This is important in the context of doxorubicin-induced cardiotoxicity as well. Doxorubicin (Dox) is an effective chemotherapy against multiple cancers but at the cost of cardiotoxicity. The innate immune system has emerged as a contributor to exacerbate the disease. In this review, we discuss the current understanding of the role of innate immunity in the pathogenesis of cardiovascular disease and dox-induced cardiotoxicity and provide potential therapeutic targets to alleviate the damage.
Quasispecies Fitness Partition to Characterize the Molecular Status of a Viral Population. Negative Effect of Early Ribavirin Discontinuation in a Chronically Infected HEV Patient
Authors: Gregori Josep , Colomer-Castell Sergi , Campos Carolina , Ibañez-Lligoña Marta , Garcia-Cehic Damir , Rando-Segura Ariadna , Adombie Caroline Melanie , Pintó Rosa , Guix Susanna , Bosch Albert , Domingo Esteban , Gallego Isabel , Perales Celia , Cortese Maria Francesca , Tabernero David , Buti Maria , Riveiro-Barciela Mar , Esteban Juan Ignacio , Rodriguez-Frias Francisco , Quer Josep
Published: November 2022

The changes occurring in viral quasispecies populations during infection have been monitored using diversity indices, nucleotide diversity, and several other indices to summarize the quasispecies structure in a single value. In this study, we present a method to partition quasispecies haplotypes into four fractions according to their fitness: the master haplotype, rare haplotypes at two levels (those present at <0.1%, and those at 0.1–1%), and a fourth fraction that we term emerging haplotypes, present at frequencies >1%, but less than that of the master haplotype. We propose that by determining the changes occurring in the volume of the four quasispecies fitness fractions together with those of the Hill number profile we will be able to visualize and analyze the molecular changes in the composition of a quasispecies with time. To develop this concept, we used three data sets: a technical clone of the complete SARS-CoV-2 spike gene, a subset of data previously used in a study of rare haplotypes, and data from a clinical follow-up study of a patient chronically infected with HEV and treated with ribavirin. The viral response to ribavirin mutagenic treatment was selection of a rich set of synonymous haplotypes. The mutation spectrum was very complex at the nucleotide level, but at the protein (phenotypic/functional) level the pattern differed, showing a highly prevalent master phenotype. We discuss the putative implications of this observation in relation to mutagenic antiviral treatment.
Immunoproteasome Inhibition Ameliorates Aged Dystrophic Mouse Muscle Environment
Authors: Tripodi Luana , Molinaro Davide , Fortunato Francesco , Mella Carolina , Cassani Barbara , Torrente Yvan , Farini Andrea
Published: November 2022

Muscle wasting is a major pathological feature observed in Duchenne muscular dystrophy (DMD) and is the result of the concerted effects of inflammation, oxidative stress and cell senescence. The inducible form of proteasome, or immunoproteasome (IP), is involved in all the above mentioned processes, regulating antigen presentation, cytokine production and immune cell response. IP inhibition has been previously shown to dampen the altered molecular, histological and functional features of 3-month-old mdx mice, the animal model for DMD. In this study, we described the role of ONX-0914, a selective inhibitor of the PSMB8 subunit of immunoproteasome, in ameliorating the pathological traits that could promote muscle wasting progression in older, 9-month-old mdx mice. ONX-0914 reduces the number of macrophages and effector memory T cells in muscle and spleen, while increasing the number of regulatory T cells. It modulates inflammatory markers both in skeletal and cardiac muscle, possibly counteracting heart remodeling and hypertrophy. Moreover, it buffers oxidative stress by improving mitochondrial efficiency. These changes ultimately lead to a marked decrease of fibrosis and, potentially, to more controlled myofiber degeneration/regeneration cycles. Therefore, ONX-0914 is a promising molecule that may slow down muscle mass loss, with relatively low side effects, in dystrophic patients with moderate to advanced disease.
Overexpression of TcNTPDase-1 Gene Increases Infectivity in Mice Infected with Trypanosoma cruzi
Authors: Silva-Gomes Natália Lins da , Ruivo Leonardo Alexandre de Souza , Moreira Claudia , Meuser-Batista Marcelo , Silva Cristiane França da , Batista Denise da Gama Jaen , Fragoso Stênio , Oliveira Gabriel Melo de , Soeiro Maria de Nazaré Correia , Moreira Otacilio C.
Published: November 2022

Ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) are enzymes located on the surface of the T. cruzi plasma membrane, which hydrolyze a wide range of tri-/-diphosphate nucleosides. In this work, we used previously developed genetically modified strains of Trypanosoma cruzi (T. cruzi), hemi-knockout (KO +/−) and overexpressing (OE) the TcNTPDase-1 gene to evaluate the parasite infectivity profile in a mouse model of acute infection (n = 6 mice per group). Our results showed significantly higher parasitemia and mortality, and lower weight in animals infected with parasites OE TcNTPDase-1, as compared to the infection with the wild type (WT) parasites. On the other hand, animals infected with (KO +/−) parasites showed no mortality during the 30-day trial and mouse weight was more similar to the non-infected (NI) animals. In addition, they had low parasitemia (45.7 times lower) when compared with parasites overexpressing TcNTPDase-1 from the hemi-knockout (OE KO +/−) group. The hearts of animals infected with the OE KO +/− and OE parasites showed significantly larger regions of cardiac inflammation than those infected with the WT parasites (p < 0.001). Only animals infected with KO +/− did not show individual electrocardiographic changes during the period of experimentation. Together, our results expand the knowledge on the role of NTPDases in T. cruzi infectivity, reenforcing the potential of this enzyme as a chemotherapy target to treat Chagas disease (CD).
Red Algae “Sarcodia suieae” Acetyl-Xylogalactan Downregulate Heat-Induced Macrophage Stress Factors Ddit3 and Hyou1 Compared to the Aquatic Animal Model of Nile Tilapia (Oreochromis niloticus) Brain Arachidonic Acid Expression
Authors: Pan Po-Kai , Wang Kuang-Teng , Nan Fan-Hua , Wu Tsung-Meng , Wu Yu-Sheng
Published: November 2022

Anthropogenic climate change is known to be an increased stress that affects aquatic animal behavior and physiological alternations, which can induce the animal’s death. In order to known whether the extracted acetyl-xylogalactan function on the regulation of the external high temperature induced death, we first selected the mammalian cell line “RAW 264.7” used in the previous experiment to evaluate the extracted acetyl-xylogalactan function. We aimed to evaluate the effects of the acetyl-xylogalactan on the RAW 264.7 macrophages and Nile Tilapia stress factor expression under the heat environment. In the in vitro cell observation, we assessed the cell survival, phagocytic activity, intracellular Ca2+ level, mitochondria potential exchange, apoptotic assay findings, galactosidase activity, RNA-seq by NGS and real-time polymerase chain reaction (QPCR) expression. In the in vivo Nile Tilapia observation aimed to evaluate the blood biochemical indicator, brain metabolites exchange and the liver morphology. In our evaluation of RAW 264.7 macrophages, the RNA sequencing and real-time polymerase chain reaction (PCR) was shown to upregulate the expression of the anti-apoptosis Cflar gene and downregulate the expression of the apoptosis factors Ddit3 and Hyou1 to protect macrophages under heat stress. We already knew the extracted acetyl-xylogalactan function on the mammalian “RAW 264.7” system. Following, we used the aquatic Nile Tilapia model as the anthropogenic climate change high temperature experiment. After feeding the Nile Tilapia with the acetyl-xylogalactan, it was found to reduce the brain arachidonic acid (AA) production, which is related to the NF-κB-induced apoptosis mechanism. Combined with the in vitro and in vivo findings, the acetyl-xylogalactan was able to reduce the heat induced cell or tissue stress.
Regulation of P-Glycoprotein in the Brain
Authors: Chai Amanda B. , Callaghan Richard , Gelissen Ingrid C.
Published: November 2022

Maintenance of the tightly regulated homeostatic environment of the brain is facilitated by the blood–brain barrier (BBB). P-glycoprotein (P-gp), an ATP-binding cassette transporter, is expressed on the luminal surface of the endothelial cells in the BBB, and actively exports a wide variety of substrates to limit exposure of the vulnerable brain environment to waste buildup and neurotoxic compounds. Downregulation of P-gp expression and activity at the BBB have been reported with ageing and in neurodegenerative diseases. Upregulation of P-gp at the BBB contributes to poor therapeutic outcomes due to altered pharmacokinetics of CNS-acting drugs. The regulation of P-gp is highly complex, but unravelling the mechanisms involved may help the development of novel and nuanced strategies to modulate P-gp expression for therapeutic benefit. This review summarises the current understanding of P-gp regulation in the brain, encompassing the transcriptional, post-transcriptional and post-translational mechanisms that have been identified to affect P-gp expression and transport activity.
Mechanisms of Resistance and Strategies to Combat Resistance in PD-(L)1 Blockade
Authors: Moise John , Murthy Jeevan , Dabir Dolma , Yu Stephen , Kisto Farah , Herron Emily , Aulakh Sonikpreet
Published: November 2022

Prolonged survival and durable responses in several late-stage cancers such as melanoma and lung cancer have been made possible with the use of immune checkpoint inhibitors targeting the programmed cell-death protein 1 (PD-1) or its ligand PD-L1. While it is prudent to focus on the unprecedented and durable clinical responses, there are subsets of cancer patients that do not respond to immunotherapies or respond early and then relapse later. Many pathways of resistance have been characterized, and more continue to be uncovered. To overcome the development of resistance, an in-depth investigation is necessary to identify alternative immune receptors and signals with the overarching goal of expanding treatment options for those with demonstrated resistance to PD1 checkpoint immunotherapy. In this mini-review, we will discuss the mechanisms by which tumors exhibit resistance to anti-PD-1/PD-L1 immunotherapy and explore strategies to overcome such resistances.
Identification of Sliding Hiatus Hernia by High-Resolution Manometry and Upper Gastrointestinal Endoscopy in Patients with Gastro-Oesophageal Reflux Disease
Authors: Stadnicki Antoni , Kurek Józef , Klimacka-Nawrot Ewa , Stadnicka Anna , Rerych Katarzyna
Published: November 2022

Background/Aim: The aim of this study was to compare high-resolution manometry (HRM) and upper gastrointestinal (GI) endoscopy as diagnostic utilities in detecting a sliding hiatus hernia in patients with gastro-oesophageal reflux disease (GORD) symptoms. Material and Methods: For both diagnostic modalities, the data obtained from 31 patients (20 females; mean age 48.2) who qualified for Nissen fundoplication were analysed using oesophageal pressure topography in line with the Chicago Classification. Confirmation of hiatus hernia during the surgery was considered the gold standard. HRM protocol involved 10 consecutive boluses of 10 mL of water. Results: Sliding hiatus hernia was confirmed intraoperatively in 29 out of 31 patients. In 14 patients, hiatus hernia was detected in HRM, while 19 patients were found to have hiatus hernia by upper GI endoscopy before surgery. No false positive results were obtained in HRM, while 15 false negative results were shown. In upper GI endoscopy, false positive data were observed in 1 patient, while false negative results were found in 10 patients. Thus, the sensitivity of HRM in detecting hiatus hernia was 48% (95%CIs: 29–67%), and sensitivity of upper GI endoscopy was 66% (95%CIs: 46–82%). It was not possible to assess the specificity of HRM or upper GI endoscopy because only 2 of 31 patients had no hiatus hernia during fundoplication (gold standard). False negative results (sensitivity) were not significantly different between compared diagnostic modalities HRM and upper GI endoscopy (52% vs. 34%, respectively, p = 0.29). Conclusions: Due to poor sensitivity, both modalities, i.e., HRM and upper GI endoscopy, are not reliable tools to diagnose sliding hiatus hernia in patients with GORD symptoms.
Eryptosis in Peritoneal Dialysis-Related Peritonitis: The Potential Role of Inflammation in Mediating the Increase in Eryptosis in PD
Authors: Virzì Grazia , Milan Manani Sabrina , Marturano Davide , Clementi Anna , Lerco Silvia , Tantillo Ilaria , Giuliani Anna , Battaglia Giovanni , Ronco Claudio , Zanella Monica
Published: November 2022

Background: Peritonitis and exit site infections are the main complications of patients treated with peritoneal dialysis (PD). Erythrocytes (red blood cells—RBCs) are very sensitive cells, and they are characterized by eryptosis (programmed cell death). The purpose of this research was to assess eryptosis in PD patients with PD-related peritonitis and its connection to inflammatory markers in vivo and in vitro. Material and Methods: In this study, we included 65 PD patients: 34 PD patients without systemic inflammation nor PD-related peritonitis in the previous 3 months, and 31 PD patients with an acute episode of PD-related peritonitis. We measured C-reactive protein (CRP) and cytokine (IL-1β, IL-6, and IL-18) levels as systemic inflammatory markers. Eryptosis was evaluated by flow cytometric analyses in freshly isolated RBCs. The induction of eryptosis due to in vitro exposure to IL-1β, IL-6, and IL-18 was verified. Results: Eryptosis was significantly higher in PD patients with peritonitis (9.6%; IQR 4.2–16.7), compared to the those in the other group (2.7%; IQR 1.6–3.9) (p < 0.0001). Significant positive correlations were noticed between eryptosis and CRP, IL-1β, and IL-6. RBCs, incubated with greater concentrations of all cytokines in vitro, resulted in significantly higher occurrences of eryptosis in comparison with those incubated with lower concentration and with untreated cell (p < 0.05), and for those with extensive exposure (p < 0.05). Conclusion: In conclusion, we investigated a potential relationship between systemic eryptosis and the in vivo and in vitro inflammatory damage of the peritoneal membrane during peritonitis. Thus, the presented results revealed that upregulated inflammatory markers and immune system dysregulation could be the cause of high levels of systemic eryptosis during PD-related peritonitis.
Measurements of Anterior and Posterior Corneal Curvatures with OCT and Scheimpflug Biometers in Patients with Low Total Corneal Astigmatism
Authors: Muzyka-Woźniak Maria , Oleszko Adam , Grzybowski Andrzej
Published: November 2022

Background: Posterior keratometry measurements are evolving features of the optical biometers. The differences between devices have bigger impact for the low astigmatism values. The majority of adults present the corneal astigmatism below 1.5 D. Objectives: To compare the total corneal astigmatism measured with two different technologies in cataract patients with corneal astigmatism below 1.5 D. Material and Methods: Three automated exams were performed on each of the two devices: swept-source optical coherence tomography (SS-OCT) and Scheimpflug biometers. The anterior and total corneal astigmatism and power were analysed. Statistical comparisons were performed for within-subject standard deviation, repeatability, Bland–Altman and vector analysis. Results: Twenty-nine eyes of twenty-seven patients were included. The limits of agreement between anterior and total corneal astigmatism were narrower for the SS-OCT than for the Scheimpflug biometer (−0.16 to 0.29 D and −0.40 to 0.39 D, respectively). The >0.5 D difference between SS-OCT and Scheimpflug total astigmatism was noticed in 5 (17%) of cases. The difference between mean total keratometric power for both devices was statistically significant (0.2 D, p < 0.001). SS-OCT total corneal flat measurements had worse repeatability than Scheimpflug (p = 0.007). Conclusions: For the corneal astigmatism <1.5 D, the difference between anterior and total corneal astigmatism measured with SS-OCT was clinically not significant. The mean anterior and total keratometry values obtained with Scheimpflug and SS-OCT biometers are not interchangeable.
Conjunctival Swabs Reveal Higher Detection Rate Compared to Schirmer Strips for SARS-CoV-2 RNA Detection in Tears of Hospitalized COVID-19 Patients
Authors: Sabage Luís Expedito , Sun Young Joo , Wolf Julian , Sabage Josmar , Mazzo Alessandra , Santos Carlos Ferreira , Mahajan Vinit B. , Manzoni Lourençone Luiz Fernando
Published: November 2022

Purpose: To determine the prevalence of SARS-CoV-2 in tear samples and to investigate whether it correlates with ocular findings and patients’ prognosis in Brazil. Methods: Tears were collected using Schirmer strips (SS) and conjunctival swabs (CS) from patients hospitalized with laboratory-confirmed SARS-CoV-2 infection. Samples were analyzed using qRT-PCR. Demographic and clinical data, ocular symptoms, and Schirmer tests (ST) were collected from patients. Charlson Comorbidity Index (CCI) was used to rate comorbidities, and patients were monitored until hospital discharge or death. Results: There were 61 hospitalized patients, 33 of which were diagnosed with COVID-19. Within the confirmed COVID-19 patients, SARS-CoV-2 was detected in 18.2% (n = 6) of CS and 12.1% (n = 4) of SS samples. Subjective and objective parameters for dry eye syndrome (e.g., ST COVID-19: 8.3 ± 6.4mm, non-COVID-19: 8.9 ± 6.6mm, p > 0.05) were comparable between COVID-19 (n = 33) and non-COVID-19 patients (n = 28). Among the 16 COVID-19 patients exhibiting ocular symptoms, only tearing was reported significantly more frequently when tear samples were positive for SARS-CoV-2 (p < 0.05). Strikingly, patients whose tears tested positive for SARS-CoV-2 had significantly inferior CCI (pos.: 34.0 ± 31.8%, neg.: 67.6 ± 36.4%, p < 0.05) and higher mortality rates (pos.: 50.0%, neg.: 7.4%, p < 0.01). Conclusions: SARS-CoV-2 was detected with a prevalence of 18.2% on the ocular surface. Decreased CCI and increased mortality rate in the positive tear group suggests that viral detection may relate to prognosis and highlight the need of personal protective measures for healthcare professionals. Most of the patients, regardless of COVID-19 diagnosis, had low tear production and eye discomfort, possibly pointing to the need for artificial tear use during hospitalization.
Color Image Enhancement Focused on Limited Hues
Authors: Azetsu Tadahiro , Suetake Noriaki , Kohashi Keisuke , Handa Chisa
Published: November 2022

Some color images primarily comprise specific hues, for example, food images predominantly contain a warm hue. Therefore, these hues are essential for creating delicious impressions of food images. This paper proposes a color image enhancement method that can select hues to be enhanced arbitrarily. The current chroma is considered such that near achromatic colors are not over-enhanced. The effectiveness of the proposed method was confirmed through experiments using several food images.
Branch-And-Price Algorithm for the Tramp Ship Routing and Scheduling Problem Considering Ship Speed and Payload
Authors: Li Lingzi , Ji Bin , Yu Samson S. , Zhou Saiqi , Fang Xiaoping
Published: November 2022

In recent years, increasing fuel prices, depressed market conditions and air pollution issues have brought huge challenges to the tramp shipping industry. This work investigates the tramp ship routing and scheduling problem considering ship speeds and payloads, aiming at minimizing ship fuel consumption. A mixed integer non-linear programming model with a discretized speed variable and a set partitioning model for this problem is established, and a branch-and-price algorithm is proposed to solve the problem. Through the column generation approach, the problem at each branch-and-bound node is decomposed into a linear programming master problem and a pricing problem of the elementary shortest path with resource constraints. A labeling algorithm is adopted for solving the pricing problem. Multiple groups of instances are generated to test the effectiveness of the proposed model and algorithm and analyze the impacts of ship speed, payload, and speed discretization on the solution. Computational experiments are conducted, which verifies the proposed scheduling routing method for tramp ships and confirms that adopting the proposed model can effectively reduce fuel consumption of tramp ships which can not only deepen the theory of tramp routing and scheduling, but also provide theoretical guidance to tramp ship company. The branch-and-price algorithm can effectively solve large-scale tramp ship routing and scheduling problems. Reasonable number of speed discretization points can bring a desirable trade-off between solution accuracy and algorithm runtime.
Analysis of OTT Users’ Watching Behavior for Identifying a Profitable Niche: Latent Class Regression Approach
Authors: Shim Dongnyok , Lee Changjun , Oh Inha
Published: November 2022

Over-the-top (OTT) firms must overcome the hurdle of the competitive Korean media market to achieve sustainable growth. To do so, understating how users enjoy OTT and analyzing usage patterns is essential. This research aims to empirically identify a profitable niche in the Korean OTT market by applying market segmentation theory. In addition, it investigates an effective content strategy to convert free users into paying customers belonging to profitable niche segments. The latent class regression model was applied to Korean Media Panel Survey data to divide Korean OTT customers into submarkets. According to an empirical analysis, Korean OTT users can be divided into three submarkets based on their OTT usage patterns, with the third segment serving as a profitable niche market. An additional analysis of the profitable niche market revealed that bundling content, such as foreign content, original content, and movies, is a crucial content strategy for increasing paying subscribers in a profitable niche segment.
Analyzing the Structure of Residence–Leisure Network in Shenyang City
Authors: Ma Liya , Xiu Chunliang
Published: November 2022

Leisure is an important part of the daily activities of urban residents. A relatively dense flow of people will be generated between residential areas and supermarkets, as well as between residential areas and highly popular park facilities. These flows of people can reflect the characteristics of residents’ leisure activities and the spatial characteristics of urban residence–leisure functions, as opposed to static leisure facilities and places; it is a new perspective for the study of urban spatial structure. Network studies on the relationship between residential and leisure functions within cities are rarely seen. In this study, from the flow space perspective, based on the questionnaire data, points of interest data, and mobile phone signaling data, the actual leisure travel flows of residents with different travel purposes can be identified, including residence–shopping leisure flows and residence–park leisure flows, and the corresponding urban networks can be constructed from them. With the help of complex network analysis, this paper discusses different types of residence–leisure network structures and their influencing factors in terms of network characteristics, node strength, and QAP analysis. It deepens the understanding of the urban spatial structure and provides the theoretical basis and technical support for urban structure analysis, urban layout optimization, and urban planning and management. The results show that: ① Both residence–shopping leisure and residence–park leisure networks have the small-world characteristics and scale-free properties of complex networks. ② The characteristics of the nodes of the residence–leisure network for different leisure travel purposes indicate that residents go more to Taiyuan Street and the New North Station business circle for shopping activities, and the parks that attract residents to go out for walks are concentrated in the central part of the city. ③ Different types of network structures have a strong correlation with the number of residential functions and leisure facilities but have a weak correlation with the difference in the number of inhabitants and leisure travel distance. This study enriches the research cases of the urban residence–leisure network structure to a certain extent. Shenyang City has the same background of rapid expansion as other large cities in China, and this study has an important role in planning and inspiration for solving urban diseases and achieving the orderly and rational development of large cities.
Environmental Suitability Evaluation for Human Settlements of Rural Residential Areas in Hengshui, Hebei Province
Authors: Yu Lu , Xie Dinglong , Xu Xiang
Published: November 2022

To improve the development quality of rural residential areas in plain areas requires scientific evaluation. Based on the rural residential area in Hengshui City, Hebei Province, the study selected four indicators of location, production, ecology, and management, to build an evaluation model for the suitability of human settlements and evaluated rural residential areas in Hengshui City. The findings indicated the following: (1) The most suitable areas are mainly concentrated in the geographical center of Hengshui City. The generally suitable areas are mainly distributed in the east of the city. The basic suitable areas are scattered in the west and northeast of the city. The unsuitable areas are mainly concentrated in the north of the city. Most of the area of Hengshui City is suitable for the residence and development of rural residential areas, and 72.86% of rural residential areas are located in suitable areas, which is consistent with the geographical environment characteristics of plain areas. (2) The rural residential areas in unsuitable areas are mainly due to the low income, serious population loss and low urbanization rate, which are in line with the characteristics of rural residential areas. (3) The suitability of human settlements in rural residential areas in plain areas is mainly affected by the per capita agricultural land area, hydrology index, distance to river, distance to country, distance to a slow road, and distance to the fast road are low-level driving factors, of which distance to a fast road has the weakest influence. (4) There is a significant positive correlation between the environmental suitability and the distribution density of rural residential areas. The improvement of the suitability of human settlements can effectively promote the aggregation and distribution of rural residential areas. High-high clustering areas are mainly concentrated in the middle and northeast of Hengshui City, while low-low clustering areas are scattered in the north and southwest of Hengshui City. (5) The location index (LI) and management index (AI) play a limiting role in the suitability of human settlements in the northeast of Hengshui City, and the government should strengthen management intervention and infrastructure construction in the northeast of Hengshui City. The production index (PI) plays a limiting role in the suitability of human settlements in the west of Hengshui City and should consider the improvement of production capacity in the west of Hengshui City. The research results play a vital role in improving the carrying capacity of regional resources and the environment in the plain area, improving rural production, and living conditions, and promoting the development of rural planning in the whole region.
Quercetin Derivatives in Combating Spinal Cord Injury: A Mechanistic and Systematic Review
Authors: Fakhri Sajad , Gravandi Mohammad Mehdi , Abdian Sadaf , Moradi Seyed Zachariah , Echeverría Javier
Published: November 2022

Spinal cord injury (SCI) possesses a complicated etiology. There is no FDA-approved treatment for SCI, and the majority of current interventions focus on reducing symptoms. During SCI, inflammation, oxidative stress, apoptosis, and autophagy are behind the secondary phase of SCI and cause serious consequences. It urges the need for providing multi-targeting agents, that possess lower side effects and higher efficacy. The plant secondary metabolites are multi-targeting agents and seem to provide new roads in combating diseases. Flavonoids are phytochemicals of continual interest to scientists in combating neurodegenerative diseases (NDDs). Flavonoids are being studied for their biological and pharmacological effects, particularly as antioxidants, anti-inflammatory agents, anti-apoptotic, and autophagy regulators. Quercetin is one of the most well-known flavonols known for its preventative and therapeutic properties. It is a naturally occurring bioactive flavonoid that has recently received a lot of attention for its beneficial effects on NDDs. Several preclinical evidence demonstrated its neuroprotective effects. In this systematic review, we aimed at providing the biological activities of quercetin and related derivatives against SCI. Detailed neuroprotective mechanisms of quercetin derivatives are also highlighted in combating SCI.
Analysis of the Potential Relationship between Aging and Pulmonary Fibrosis Based on Transcriptome
Authors: Fu San , Tang Xiaoyan , Xu Yiming , Song Xianrui , Qian Xiuhui , Hu Yingying , Zhang Mian
Published: November 2022

Idiopathic pulmonary fibrosis (IPF) is an age-related interstitial lung disease with a high incidence in the elderly. Although many reports have shown that senescence can initiate pulmonary fibrosis, the relationship between aging and pulmonary fibrosis has not been explained systematically. In our study, young and old rats were intratracheally instilled with bleomycin (1 mg/kg), and the basic pathological indexes were determined using a commercial kit, hematoxylin, and eosin (H&E) and Masson’s Trichrome staining, immunohistochemistry, immunohistofluorescence, and q-PCR. Then, the lung tissues of rats were sequenced by next-generation sequencing for transcriptome analysis. Bioinformatics was performed to analyze the possible differences in the mechanism of pulmonary fibrosis between aged and young rats. Finally, the related cytokines were determined by q-PCR and ELISA. The results indicate that pulmonary fibrosis in old rats is more serious than that in young rats under the same conditions. Additionally, transcriptomic and bioinformatics analysis with experimental validation indicate that the differences in pulmonary fibrosis between old and young rats are mainly related to the differential expression of cytokines, extracellular matrix (ECM), and other important signaling pathways. In conclusion, aging mainly affects pulmonary fibrosis through the ECM–receptor interaction, immune response, and chemokines.
Temporal Compression in Shakespeare’s Richard III
Authors: Innes Paul , James Katie
Published: November 2022

Shakespeare’s treatment of Richard III has long been the cause of debates about Tudor defamations of the last Yorkist king. Within this context, some attention has been paid to the play’s extreme compression of events that in fact took place over a period of seven years, from the death of George, Duke of Clarence in 1478 to the Battle of Bosworth Field in 1485. This study investigates the momentum of events to gauge the extent to which the representation of Richard does paint him in an entirely negative light. Detailed analysis of the timeline demonstrates that the way the play re-structures historical moments is designed to foreground not only the figure of Richard himself, with all its attendant associations, but also the very methods used to concentrate attention upon him. The self-referential nature of the play’s relationship to history points to its own constructions, foregrounding the techniques used to show not only the legend of Richard, but how it is elaborated. The play therefore draws attention to its own manipulation of events, which in turn makes any assumptions about its representation of Richard as villain open to question.
A Class of Singular Sturm–Liouville Problems with Discontinuity and an Eigenparameter-Dependent Boundary Condition
Authors: Cai Jinming , Zheng Zhaowen , Li Kun
Published: November 2022

In this paper, we study a singular Sturm–Liouville problem with an eigenparameter-dependent boundary condition and transmission conditions at two interior points. Using an operator-theoretical formulation, we transfer the problem to an operator in an appropriate Hilbert space. It is proved that the operator is self-adjoint. We also give the asymptotic formulas of the eigenvalues of the problem. Moreover, Green’s function is also discussed.
Frequency and Antibiotic Susceptibility Patterns of Streptococcus agalactiae Strains Isolated from Women in Yaounde, Cameroon
Authors: Djuikoue Cécile Ingrid , Djoulako Paule Dana Djouela , Wouambo Rodrigue Kamga , Foutsa Rosine Yemetio , Ngatcheu Dorine Ekeu , Apalata Teke
Published: November 2022

Group B Streptococcus (GBS), a commensal in the body, causes a wide range of infectious diseases. This bacterium is dangerous for pregnant women and their babies, in whom it is responsible for early neonatal bacterial sepsis (EOS). The colonisation levels of GBS and its resistance profile to antibiotics provide important information that is useful for orienting prevention strategies. There are few data available on the subject on the determination of resistance phenotypes in Cameroon. We therefore aimed to determine the prevalence of colonisation and antibiotic resistance, including patterns of inducible resistance to clindamycin, of GBS in the city of Yaounde. To achieve this goal, a prospective cross-sectional study with an analytical component was carried out from 28 June to 29 August 2020 at the BIOSANTE laboratory and the Yaounde Gynaeco-Obstetrics and Paediatrics hospital. Vaginal swabs and urine were collected from 163 women. This samples were analysed using 5% defibrinated sheep blood agar and chocolate plus polyvitex agar. The isolates were identified using the morphology of the colony, Gram staining, haemolysis, catalase tests and latex grouping tests. Antibiotic susceptibility testing was carried out by disk diffusion method following the recommendations of the ACFSM 2019. The double disk diffusion method was used to identify isolates with clindamycin-inducible resistance. Our data were analysed with SPSS version 2.1. The results obtained showed that the overall prevalence of colonisation by GBS was 37% (57/163), or 40.3% in non-pregnant women and 59.7% in pregnant women. Pregnancy (p-value = 0.019) and earlier (from the second semester of pregnancy) gestational age (p-value = 0.025) constituted the risk factors of maternal colonisation by GBS. In addition, the strains of GBS were resistant to all 16 antibiotics tested. A D test showed that 64.7% of GBS strains were constitutively resistant to clindamycin. We also note the presence of M phenotypes. As a whole, our results demonstrated that the rate of GBS colonisation in this study was similar to or higher than those in previous reports in Cameroon. All these results indicate that attention should be paid to this bacterium in the monitoring of antimicrobial resistance and in the care of pregnant women and newborns.
Theileria terrestris nov. sp.: A Novel Theileria in Lowland Tapirs (Tapirus terrestris) from Two Different Biomes in Brazil
Authors: Mongruel Anna Claudia Baumel , Medici Emília Patrícia , da Costa Canena Ariel , Calchi Ana Cláudia , Perles Lívia , Rodrigues Bianca Cardenal Balla , Soares João Fabio , Machado Rosangela Zacarias , André Marcos Rogério
Published: November 2022

The low-land tapir (Tapirus terrestris) is the largest wild terrestrial mammal found in Brazil. Although T. terrestris has been already reported as a host of hemoparasites, the occurrence and genetic identity of Piroplasmida agents in this species is still cloudy. Although it is reported that Theileria equi, an endemic equid-infective agent in Brazil, is occurring in lowland tapirs, these reports are probably misconceived diagnoses since they are solely based on small fragments of 18S rRNA that may not achieve accurate topologies on phylogenetic analyses. The present study aimed to detect and investigate the identity of Theileria spp. in tapirs from Pantanal and Cerrado biomes. Blood-DNA samples from tapirs were screened for a partial (~800 bp) 18S rRNA gene fragment from Piroplasmida and 64 (64/122; 52.46% CI: 43.66–61.11%) presented bands of expected size. Samples were submitted to different protocols for molecular characterization, including near-full length 18S rRNA gene (~1500 bp), and the ema-1 gene from T. equi. Eight sequences were obtained for extended fragments (1182–1473 bp) from the 18S rRNA gene. Moreover, three sequences from partial cox-1 and five from partial hsp70 gene were obtained. None of the samples presented amplifications for the ema-1 gene. Phylogenetic and distance analyses from the 18S rRNA sequences obtained demonstrated a clear separation from tapirs’ Theileria spp. and T. equi. Phylogenetic analyses of cox-1 and hsp70 sequences obtained herein also showed a unique clade formed by tapir’s Theileria spp. Theileria terrestris sp. nov. is positioned apart from all other Theileria species in 18S rRNA, cox-1, and hps70 phylogenetic analyses. This novel proposed species represents a new Piroplasmida clade, yet to be characterized regarding biological features, vectors involved in the transmission cycles, additional vertebrate hosts, and pathogenicity.
Closing the Gap between Bio-Based and Petroleum-Based Plastic through Bioengineering
Authors: Al-Khairy Dina , Fu Weiqi , Alzahmi Amnah Salem , Twizere Jean-Claude , Amin Shady A. , Salehi-Ashtiani Kourosh , Mystikou Alexandra
Published: November 2022

Bioplastics, which are plastic materials produced from renewable bio-based feedstocks, have been investigated for their potential as an attractive alternative to petroleum-based plastics. Despite the harmful effects of plastic accumulation in the environment, bioplastic production is still underdeveloped. Recent advances in strain development, genome sequencing, and editing technologies have accelerated research efforts toward bioplastic production and helped to advance its goal of replacing conventional plastics. In this review, we highlight bioengineering approaches, new advancements, and related challenges in the bioproduction and biodegradation of plastics. We cover different types of polymers, including polylactic acid (PLA) and polyhydroxyalkanoates (PHAs and PHBs) produced by bacterial, microalgal, and plant species naturally as well as through genetic engineering. Moreover, we provide detailed information on pathways that produce PHAs and PHBs in bacteria. Lastly, we present the prospect of using large-scale genome engineering to enhance strains and develop microalgae as a sustainable production platform.