bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra-Articular Mesenchymal Stem Cell Injection for Knee Osteoarthritis: Mechanisms and Clinical Evidence
Authors: Wei Pengxu , Bao Ruixue
Published: December 2022

Knee osteoarthritis presents higher incidences than other joints, with increased prevalence during aging. It is a progressive process and may eventually lead to disability. Mesenchymal stem cells (MSCs) are expected to repair damaged issues due to trilineage potential, trophic effects, and immunomodulatory properties of MSCs. Intra-articular MSC injection was reported to treat knee osteoarthritis in many studies. This review focuses on several issues of intra-articular MSC injection for knee osteoarthritis, including doses of MSCs applied for injection and the possibility of cartilage regeneration following MSC injection. Intra-articular MSC injection induced hyaline-like cartilage regeneration, which could be seen by arthroscopy in several studies. Additionally, anatomical, biomechanical, and biochemical changes during aging and other causes participate in the development of knee osteoarthritis. Conversely, appropriate intervention based on these anatomical, biomechanical, biochemical, and functional properties and their interactions may postpone the progress of knee OA and facilitate cartilage repair induced by MSC injection. Hence, post-injection rehabilitation programs and related mechanisms are discussed.
Design and Synthesis of Acridine-Triazole and Acridine-Thiadiazole Derivatives and Their Inhibitory Effect against Cancer Cells
Authors: Huo Lini , Liu Xiaochen , Jaiswal Yogini , Xu Hao , Chen Rui , Lu Rumei , Nong Yaqin , Williams Leonard , Liang Yan , Jia Zhiruo
Published: December 2022

We report herein the design and synthesis of a series of novel acridine-triazole and acridine-thiadiazole derivatives. The newly synthesized compounds and the key intermediates were all evaluated for their antitumor activities against human foreskin fibroblasts (HFF), human gastric cancer cells-803 (MGC-803), hepatocellular carcinoma bel-7404 (BEL-7404), large cell lung cancer cells (NCI-H460), and bladder cancer cells (T24). Most of the compounds exhibited high levels of antitumor activity against MGC-803 and T24 but low toxicity against human normal liver cells (LO2), and their effect was even better than the commercial anticancer drugs, 5-fluorouracil (5-FU) and cis-platinum. Further, pharmacological mechanisms such as topo I, cell cycle, cell apoptosis, and neovascularization were all evaluated. Only a few compounds exhibited potent topo I inhibitory activity at 100 μM. In addition, the most active compounds with an IC50 value of 5.52–8.93 μM were chosen, and they could induce cell apoptosis in the G2 stage of MGC-803 or mainly arrest T24 cells in the S stage. To our delight, most of the compounds exhibited lower zebrafish cytotoxicity but could strongly inhibit the formation of zebrafish sub-intestinal veins, indicating a potential for clinical application.
Old and Promising Markers Related to Autophagy in Traumatic Brain Injury
Authors: Livieri Tommaso , Cuttaia Calogero , Vetrini Raffaella , Concato Monica , Peruch Michela , Neri Margherita , Radaelli Davide , D’Errico Stefano
Published: December 2022

Traumatic brain injury (TBI) is one of the first causes of death and disability in the world. Because of the lack of macroscopical or histologic evidence of the damage, the forensic diagnosis of TBI could be particularly difficult. Considering that the activation of autophagy in the brain after a TBI is well documented in literature, the aim of this review is to find all autophagy immunohistological protein markers that are modified after TBI to propose a method to diagnose this eventuality in the brain of trauma victims. A systematic literature review on PubMed following PRISMA 2020 guidelines has enabled the identification of 241 articles. In all, 21 of these were enrolled to identify 24 markers that could be divided into two groups. The first consisted of well-known markers that could be considered for a first diagnosis of TBI. The second consisted of new markers recently proposed in the literature that could be used in combination with the markers of the first group to define the elapsed time between trauma and death. However, the use of these markers has to be validated in the future in human tissue by further studies, and the influence of other diseases affecting the victims before death should be explored.
Lipids in Atherosclerosis: Pathophysiology and the Role of Calculated Lipid Indices in Assessing Cardiovascular Risk in Patients with Hyperlipidemia
Authors: Gaggini Melania , Gorini Francesca , Vassalle Cristina
Published: December 2022

The role of lipids is essential in any phase of the atherosclerotic process, which is considered a chronic lipid-related and inflammatory condition. The traditional lipid profile (including the evaluation of total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein) is a well-established tool to assess the risk of atherosclerosis and as such has been widely used as a pillar of cardiovascular disease prevention and as a target of pharmacological treatments in clinical practice over the last decades. However, other non-traditional lipids have emerged as possible alternative predictors of cardiometabolic risk in addition to traditional single or panel lipids, as they better reflect the overall interaction between lipid/lipoprotein fractions. Therefore, this review deals with the lipid involvement characterizing the pathophysiology of atherosclerosis, discussing some recently proposed non-traditional lipid indices and, in the light of available knowledge, their actual potential as new additive tools to better stratify cardiovascular risk in patients with hyperlipidemia as well as possible therapeutic targets in the clinical practice.
Light-Dependent Nitrate Removal Capacity of Green Microalgae
Authors: Rani Vaishali , Maróti Gergely
Published: December 2022

In the present study, Chlamydomonas sp. MACC-216 was used to investigate total nitrate removal in TAP medium with sodium nitrate as the sole nitrogen source under several light conditions made up of permuted combinations of three light colors (referred to as blue, red, and white light) and three light intensities (50 µmol m−2 s−1, 100 µmol m−2 s−1, and 250 µmol m−2 s−1). It was observed that nitrate removal efficiency is influenced by light color as well as light intensity. Additionally, Chlamydomonas sp. MACC-216 was cultivated in synthetic wastewater under four light conditions, namely, Blue 250, Blue 125 + Red 125, Red 250, and White 250, where it showed the highest nitrate removal efficiency and nitrate reductase activity under the Blue 125 + Red 125 light condition. To observe the impact of light color on the nitrate removal capacity of Chlamydomonas sp. MACC-216, the expression of five genes participating in nitrate transport and reduction (NRT1, NRT2.1, NRT2.2, NIA, and MCP) was also analyzed; these genes showed the highest expression under the Blue 125 + Red 125 light condition. Based on the above-mentioned findings, the blue + red light combination emerged as a promising light combination for nitrate removal. Hence, our study suggests the importance of the blue + red light combination together with high light intensity, as the optimal light condition for nitrate removal from synthetic wastewater in comparison to other monochromatic lights with high light intensity.
Bacterial DNAemia in Alzheimer’s Disease and Mild Cognitive Impairment: Association with Cognitive Decline, Plasma BDNF Levels, and Inflammatory Response
Authors: Giacconi Robertina , D’Aquila Patrizia , Balietti Marta , Giuli Cinzia , Malavolta Marco , Piacenza Francesco , Costarelli Laura , Postacchini Demetrio , Passarino Giuseppe , Bellizzi Dina , Provinciali Mauro
Published: December 2022

Microbial dysbiosis (MD) provokes gut barrier alterations and bacterial translocation in the bloodstream. The increased blood bacterial DNA (BB-DNA) may promote peripheral- and neuro-inflammation, contributing to cognitive impairment. MD also influences brain-derived neurotrophic factor (BDNF) production, whose alterations contribute to the etiopathogenesis of Alzheimer’s disease (AD). The purpose of this study is to measure BB-DNA in healthy elderly controls (EC), and in patients with mild cognitive impairment (MCI) and AD to explore the effect on plasma BDNF levels (pBDNF), the inflammatory response, and the association with cognitive decline during a two-year follow-up. Baseline BB-DNA and pBDNF were significantly higher in MCI and AD than in EC. BB-DNA was positively correlated with pBDNF in AD, plasma Tumor necrosis factor-alpha (TNF-α), and Interleukin-10 (IL-10) levels in MCI. AD patients with BB-DNA values above the 50th percentile had lower baseline Mini-Mental State Examination (MMSE). After a two-year follow-up, AD patients with the highest BB-DNA tertile had a worse cognitive decline, while higher BB-DNA levels were associated with higher TNF-α and lower IL-10 in MCI. Our study demonstrates that, in early AD, the higher the BB-DNA levels, the higher the pBDNF levels, suggesting a defensive attempt; BB-DNA seems to play a role in the AD severity/progression; in MCI, higher BB-DNA may trigger an increased inflammatory response.
Association between Downstream Taste Signaling Genes, Oral Microbiome, and Severe Early Childhood Caries
Authors: de Jesus Vivianne Cruz , Mittermuller Betty-Anne , Hu Pingzhao , Schroth Robert J. , Chelikani Prashen
Published: December 2022

Polymorphisms in taste receptor genes have been shown to play a role in early childhood caries (ECC), a multifactorial, biofilm-mediated disease. This study aimed to evaluate associations between severe-ECC (S-ECC), the oral microbiome, and variants in genes that encode components of the G protein-coupled receptor (GPCR) signaling cascade involved in taste sensation. A total of 176 children (88 caries-free; 88 with S-ECC) were recruited. Analyses of 16S and ITS1 rRNA microbial genes and seven (GNAQ, GNAS, GNAT3, GNAI2, RAC1, RALB, and PLCB2) human genes were pursued using next-generation sequencing. Regression analyses were performed to evaluate associations between genetic variants, S-ECC, and the supragingival plaque microbiome. Results suggest that PLCB2 rs2305645 (T), rs1869901 (G), and rs2305649 (G) alleles had a protective effect on S-ECC (rs2305645, odds ratio (OR) = 0.27 (95% confidence interval (CI): 0.14–0.51); rs1869901, OR = 0.34 (95% CI: 0.20–0.58); and rs2305649, OR = 0.43 (95% CI: 0.26–0.71)). Variants in GNAQ, GNAS, GNAT3, PLCB2, RALB, and RAC1 were associated with oral fungal and bacterial community composition. This study revealed that three loci at PLCB2 are significantly associated with S-ECC. Variants in multiple genes were associated with the composition of dental biofilm. These findings contribute to the current knowledge about the role of genetics in S-ECC.
Reported Cases and Diagnostics of Occupational Insect Allergy: A Systematic Review
Authors: Ganseman Eva , Gouwy Mieke , Bullens Dominique M. A. , Breynaert Christine , Schrijvers Rik , Proost Paul
Published: December 2022

A significant part of adult-onset asthma is caused by occupational exposure to both high- and low-molecular-mass agents. Insects are occasionally described to cause occupational allergy in professions including anglers and fishers, laboratory workers, employees of aquaculture companies, farmers, bakers, sericulture workers and pet shop workers. Occupational insect allergies are often respiratory, causing asthma or rhinoconjunctivitis, but can be cutaneous as well. The European Union recently approved three insect species for human consumption, enabling an industry to develop where more employees could be exposed to insect products. This review overviews knowledge on occupational insect allergy risks and the tools used to diagnose employees. Despite the limited availability of commercial occupational insect allergy diagnostics, 60.9% of 164 included reports used skin prick tests and 63.4% of reports used specific IgE tests. In 21.9% of reports, a more elaborate diagnosis of occupational asthma was made by specific inhalation challenges or peak expiratory flow measurements at the workplace. In some work environments, 57% of employees were sensitized, and no less than 60% of employees reported work-related symptoms. Further development and optimization of specific diagnostics, together with strong primary prevention, may be vital to the health conditions of workers in the developing insect industry.
The Role of Helicobacter pylori Neutrophil-Activating Protein in the Pathogenesis of H. pylori and Beyond: From a Virulence Factor to Therapeutic Targets and Therapeutic Agents
Authors: Fu Hua-Wen , Lai Yu-Chang
Published: December 2022

Helicobacter pylori neutrophil-activating protein (HP-NAP), a major virulence factor of H. pylori, plays a role in bacterial protection and host inflammation. HP-NAP activates a variety of innate immune cells, including neutrophils, monocytes, and mast cells, to induce their pro-oxidant and pro-inflammatory activities. This protein also induces T-helper type 1 (Th1) immune response and cytotoxic T lymphocyte (CTL) activity, supporting that HP-NAP is able to promote gastric inflammation by activation of adaptive immune responses. Thus, HP-NAP is a potential therapeutic target for the treatment of H. pylori-induced gastric inflammation. The inflammatory responses triggered by HP-NAP are mediated by a PTX-sensitive G protein-coupled receptor and Toll-like receptor 2. Drugs designed to block the interactions between HP-NAP and its receptors could alleviate the inflammation in gastric mucosa caused by H. pylori infection. In addition, HP-NAP acts as a promising therapeutic agent for vaccine development, allergy treatment, and cancer immunotherapy. The high antigenicity of HP-NAP makes this protein a component of vaccines against H. pylori infection. Due to its immunomodulatory activity to stimulate the Th1-inducing ability of dendritic cells, enhance Th1 immune response and CTL activity, and suppress Th2-mediated allergic responses, HP-NAP could also act as an adjuvant in vaccines, a drug candidate against allergic diseases, and an immunotherapeutic agent for cancer. This review highlights the role of HP-NAP in the pathogenesis of H. pylori and the potential for this protein to be a therapeutic target in the treatment of H. pylori infection and therapeutic agents against H. pylori-associated diseases, allergies, and cancer.
Pathogenesis of Alzheimer’s Disease
Authors: Rostagno Agueda A.
Published: December 2022

Alzheimer’s disease (AD) is the most common type of dementia, accounting for 60% to 80% of all cases [...]
Physiological and Morphological Response of Argania spinosa (L.) Skeels to a Competing Liana: Case Study under Arid Climate
Authors: Boukhalef Laila , Nait Douch Aicha , Bouqbis Laila , El Asbahani Abdelhafed , Touaf Mourad , Ain-Lhout Fatima
Published: December 2022

Lianas are woody climbing plants and are thought to impact the hosting trees negatively. Ephedra altissima is a liana rising on the Moroccan endemic tree Argania spinosa (L.) Skeels. In this study, our objective was to investigate the impact of the liana on the Argan tree’s physiology and leaf morphology. For that purpose, we compared gas exchange, relative water content, photosynthetic pigment content, and leaf dry mass per unit area of Argan trees associated and not associated with the liana. Our study on individual leaves does not give evidence of the existence or absence of aboveground competition between the liana and the hosting tree. Indeed, photosynthetic rates may suggest that no aboveground competition is occurring. In contrast, pigment content suggests a shading effect of the liana on the hosting tree during the winter season. Otherwise, Argan associated with the liana exhibited a high Chl a/b ratio at the beginning of the dry season, suggesting a belowground competition for nutrient resources. On the other hand, WUEi results indicate that the impact of the liana on the Argan tree may go through seasons with belowground competition for water during spring. The increased LMA values registered in trees associated with the lianasuggest the existence of belowground competition for nutrient resources that persist throughout the year.
Numerical Investigation on Effect of Opening Ratio on Structural Performance of Reinforced Concrete Deep Beam Reinforced with CFRP Enhancements
Authors: Ali Yasar Ameer , Assi Lateef Najeh , Abas Hussein , Taresh Hussein R. , Dang Canh N. , Ghahari SeyedAli
Published: December 2022

Reinforced concrete deep beams are a vital member of infrastructures such as bridges, shear walls, and foundation pile caps. Thousands of dollars and human lives are seriously threatened due to shear failure, which have developed in deep beams containing web openings. This paper investigates numerically the overall behavior of simply supported concrete deep beams reinforced with carbon fiber-reinforced polymer (CFRP) sheets through forty specimens grouped in four groups. The numerical analysis results agreed well with the experimental results in the literature, particularly the visual failure initiation with a failure load difference of nearly 7%. Finite element analyses indicated that the presence of an opening with considerable width reduced the failure load by about 71% compared to the corresponding solid specimens. In addition, the reinforced concrete deep beam samples started to behave differently when the (b/h) ratio increased more than (2.0). The findings showed that the compression stress strut pathway had been disrupted by the web opening leading to stress redistribution, and the structure will behave as two separate members. Thus, the upper web-opening part sustained the most stress, while the part under the web-opening did not show any stress concentration. The numerical stress distribution results showed that the attributed reason is that rebars and openings helped redirect the stresses to the compression strut. Using CFRP sheets with a width of more than 160 mm significantly improved the reinforced concrete deep beam with web-opening due to the increasing confinement to the upper part of the reinforced concrete deep beams with the opening.
Prognostic Significance of Baseline Blood Glucose Levels and Glucose Variability in Severe Acute Kidney Injury: A Secondary Analysis from the RENAL Study
Authors: Xie Ying , Lin Jin , Gallagher Martin , Bellomo Rinaldo , Wang Xia , Jardine Meg , Duan Meili , Wang Amanda
Published: December 2022

Aim: To study the associations between baseline blood glucose levels (BGL), glycemic variability and clinical outcomes in patients with severe acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT). Methods: We performed a secondary analysis of the Randomized Evaluation of Normal versus Augmented Level of RRT (RENAL) study. A multivariate Cox regression model was used to assess the association between baseline BGL, glycemic variability and clinical outcomes. The primary outcome was all-cause mortality, and secondary outcomes were duration of hospital and intensive care unit (ICU) stay. Results: Baseline BGL data were available in 1404 out of 1508 patients from the RENAL study. Among them, 627 patients died within 90 days of randomization. Compared to patients in the second quartile (BGL 5.8–7.2 mmol/L), patients in the first quartile (BGL < 5.8 mmol/L) had increased mortality rate (90-day HR 1.48; p = 0.001; 28-day HR 1.47; p = 0.042). However, there were no significant differences in ICU and hospital length of stay (LOS) (p = 0.82 and p = 0.33, respectively). Glycemic variability data were from 1345 out of 1404 patients who had data for BG values within 28 days. Higher coefficient of variation (CV) (HR 1.02; P trend = 0.002) and standard deviation value (SD) (HR 1.29; P trend = 0.027) were associated with higher risk of death at day 90. Conclusions: We identified a low BGL within the normal physiological range at baseline and greater CV and SD values as significant modifiable risk factors for mortality in severe AKI patients in ICU, which may be a target for intervention.
Impact of Chronic Kidney Disease on Corneal Neuroimmune Features in Type 2 Diabetes
Authors: Asiedu Kofi , Markoulli Maria , Tummanapalli Shyam Sunder , Chiang Jeremy Chung Bo , Alotaibi Sultan , Wang Leiao Leon , Dhanapalaratnam Roshan , Kwai Natalie , Poynten Ann , Krishnan Arun V.
Published: December 2022

Aim: To determine the impact of chronic kidney disease on corneal nerve measures and dendritic cell counts in type 2 diabetes. Methods: In vivo corneal confocal microscopy images were used to estimate corneal nerve parameters and compared in people with type 2 diabetes with chronic kidney disease (T2DM-CKD) (n = 29) and those with type 2 diabetes without chronic kidney disease (T2DM-no CKD) (n = 29), along with 30 healthy controls. Corneal dendritic cell densities were compared between people with T2DM-CKD and those with T2DM-no CKD. The groups were matched for neuropathy status. Results: There was a significant difference in corneal nerve fiber density (p < 0.01) and corneal nerve fiber length (p = 0.04) between T2DM-CKD and T2DM-no CKD groups. The two diabetes groups had reduced corneal nerve parameters compared to healthy controls (all parameters: p < 0.01). Immature central dendritic cell density was significantly higher in the T2DM-CKD group compared to the T2DM-no CKD group ((7.0 (3.8–12.8) and 3.5 (1.4–13.4) cells/mm2, respectively, p < 0.05). Likewise, central mature dendritic cell density was significantly higher in the T2DM-CKD group compared to the T2DM-no CKD group (0.8 (0.4–2.2) and 0.4 (0.6–1.1) cells/mm2, respectively, p = 0.02). Additionally, total central dendritic cell density was increased in the T2DM-CKD group compared to T2DM-no CKD group (10.4 (4.3–16.1) and 3.9 (2.1–21.0) cells/mm2, respectively, p = 0.03). Conclusion: The study showed that central corneal dendritic cell density is increased in T2DM-CKD compared to T2DM-no CKD, with groups matched for peripheral neuropathy severity. This is accompanied by a loss of central corneal nerve fibers. The findings raise the possibility of additional local factors exacerbating central corneal nerve injury in people with diabetic chronic kidney disease.
Advantages of DES over BMS in Preventing the Risk of Myocardial Infarction, Ischemic Stroke, and Mortality in Various Populations
Authors: Wu Pei-Ning , Chen Jia-Hung , Yang Chuan-Pin , Hsu Jason C.
Published: December 2022

Backgrounds: Previous studies have demonstrated that drug-eluting stents (DESs) are more effective than bare metal stents (BMSs) in reducing the risk of myocardial infarction in the short term, but the long-term preventive benefits for myocardial infarction, ischemic stroke, and mortality are not clear. Objective: This study deeply analyzed the long-term (within 3 years) advantages of the use of DESs in preventing the risk of myocardial infarction, ischemic stroke, and mortality in various populations compared with those of using BMSs. Methods: This was a retrospective observational cohort study. We used the 2015–2019 claims data from Taiwan’s National Health Insurance Research Database. Patients over the age of 18 who underwent coronary stent placement (both DESs and BMSs) for the first time in 2016 were included in the study population. Propensity-score matching was applied to increase the comparability of the DES and BMS groups. We used a Cox proportional hazard regression analysis to compare the effectiveness of DESs and BMSs in preventing myocardial infarction, ischemic stroke, and all-cause mortality. A subgroup analysis was also performed. Results: In total, 21,608 cases were included in this study. Overall, the risk of myocardial infarction (aHR = 0.82; 95% CI: 0.78–0.85), ischemic stroke (aHR = 0.88; 95% CI: 0.81–0.95), and mortality (aHR = 0.61; 95% CI: 0.57–0.65) in the DES group were significantly lower than those in the BMS group. However, in some special cases, the results were not statistically significant. In particular, in patients with obesity (aHR = 2.61; 95% CI: 1.20–5.69), the DES group appeared to have a significantly higher long-term intermediate ischemic risk than the BMS group. Conclusions and Relevance: In conclusion, although DESs were more effective than BMSs in reducing the risk of long-term myocardial infarction, ischemic stroke, and mortality, this study also found that, in some cases, the advantages of DESs over BMSs were not clearly observed.
Psychopathological Determinants of Quality of Life in People with Borderline Personality Disorder
Authors: Stefanatou Pentagiotissa , Xenaki Lida Alkisti , Konstantakopoulos George , Papaiakovou Anthoula , Ralli Irene , Berk Aristea D. , Katopodi Diamantina S. , Pantagoutsou Aphrodite D. , Charitaki Aimilia , Ginieri-Coccossis Maria , Giannouli Eleni , Malogiannis Ioannis A.
Published: December 2022

Background: Subjective quality of life (SQOL) in people with borderline personality disorder (BPD) is a marker of disease burden; a crucial treatment outcome; an indicator of psychosocial functioning; and a measure of interventions’ effectiveness. Given the dearth of consolidated data, the current study examined psychopathological determinants of global and domain-specific SQOL in people with BPD. Methods: Hierarchical regression models were employed to examine in BPD patients (n = 150) the relationships of the number of BPD diagnostic criteria; the co-occurrence of other personality disorders (PDs); depression; state and trait anxiety; suicidality; self-harming; alcohol and substance use disorders with SQOL indices, namely physical health, psychological health, social relationships, environment, overall QOL and overall health. SQOL was estimated using the WHOQOL-BREF instrument. Results: Co-existing symptomatology such as depression, state and trait anxiety, and personality pathology, namely the co-occurrence of other PDs, exhibited significant associations with global and domain-specific SQOL, albeit depression was the strongest determinant of the most SQOL domains. In contrast, the number of BPD diagnostic criteria and central illness features such as suicidality, self-harming behaviour, and impulsivity manifested through alcohol and substance use did not exhibit significant associations with any SQOL dimension. Conclusions: Comprehensive assessment of depressive symptoms should be regularly implemented in BPD services to facilitate early detection and treatment, thereby ensuring patients’ SQOL. Accordingly, tackling anxiety and other PDs co-occurrence through appropriate interventions can facilitate more effectively SQOL improvement. Our findings can be explained by the hypothesis that co-existing psychopathology such as depression, anxiety and co-occurrence of other PDs in BPD patients represent illness severity indices rather than comorbid disorders, and might fully mediate the effect of BPD traits on SQOL. Future mediation analysis is required to elucidate this hypothesis.
Safety Profile of Molnupiravir in the Treatment of COVID-19: A Descriptive Study Based on FAERS Data
Authors: Santi Laurini Greta , Montanaro Nicola , Motola Domenico
Published: December 2022

Concerns have been raised about the actual benefit and safety of molnupiravir, a new antiviral treatment for coronavirus disease 2019 (COVID-19). In order to provide additional evidence to support its use, we aimed to evaluate the real safety profile based on post-marketing pharmacovigilance data. Molnupiravir safety data were captured from the FDA Adverse Event Reporting System (FAERS). We performed a descriptive analysis of the baseline demographic characteristics of patients who experienced at least one adverse drug reaction (ADRs) related to molnupiravir, and then evaluated those most frequently reported. As of 31 March 2022, 612 reports of ADRs related to molnupiravir were submitted to the FDA, 301 (49.18%) were related to females and 281 (45.92%) to males. Most reports (524; 85.62%) were submitted by healthcare professionals and 345 (56.37%) concerned serious outcomes. The most common reported ADRs were diarrhoea (57; 4.51%), rash (36; 2.85), nausea (29; 2.30%), and COVID-19 pneumonia (22; 1.74%). The most frequent adverse reactions reported with molnupiravir in the U.S. post-marketing experience are consistent with the safety evaluation of the antiviral medicine. Even if no evident safety concerns emerged, an unexpectedly high rate of serious adverse reactions together with a few cases of potential new adverse reactions occurred.
The Concordance of Alveolar Bone Deficiency with Severity of Lip Deformity in Microform Cleft Lip
Authors: Jo Taehee , Choi Kyehoon , Choi Jaehoon , Kim Junhyung , Han Kihwan , Jeong Woonhyeok
Published: December 2022

Background: We assessed the anthropometric measurements of bone defects in microform cleft lip. Methods: The external phenotypes of the nose and upper lip, and alveolar bone defects in microform cleft lip were measured anthropometrically using multimodal tools and clinical photographs. The height and thickness of the alveolar bone, paranasal hypoplasia, and alveolar volume were measured on CT. Results: Our study included 23 patients with unilateral microform cleft lip. The mean age of the patients was 13.84 ± 12.35 years (range: 1.25–50 years). Alveolar height (C1), thickness (C2), and paranasal hypoplasia (C3) were evaluated on 3D CT scans. The mean differences in C1, C2, and C3 between the cleft and normal sides were 5.52 ± 3.76 mm (p < 0.0001), 1.96 ± 2.8 mm (p < 0.0001), and 5.57 ± 9.72 mm (p < 0.0001), respectively. There was bony deficiency at the cleft side of the alveolar bone and paranasal area. In volumetric analysis, the means of the normal and cleft-side alveolar bone volumes were 6579 ± 2200 mm3 and 6528 ± 2255 mm3, respectively. The mean difference in alveolar bone volume between the cleft and normal sides was 51.05 ± 521 mm3 (p < 0.0001). C1 was positively correlated with lip height (F2; correlation coefficient (r) = 0.564, p = 0.0051) and dry vermilion thickness (F3; r = −0.543, p = 0.0074). The linear regression test revealed significant correlations between C1 and F2 (r2 = 0.318, p = 0.0051), and F3 (r2 = 0.295, p = 0.0074). However, there was no correlation between alveolar height and nasal anthropometric measurements. Conclusions: Alveolar bone deficiency was concordant with the severity of soft tissue in microform cleft lip.
Predictive Value of Motor Evoked Potentials in the Resection of Intradural Extramedullary Spinal Tumors in Children
Authors: Antkowiak Lukasz , Putz Monika , Sordyl Ryszard , Pokora Szymon , Mandera Marek
Published: December 2022

This study aimed to evaluate the predictive value of motor evoked potentials (MEP) in the resection of pediatric intradural extramedullary (IDEM) tumors. Additionally, we aimed to assess the impact of MEP alerts on the extent of tumor resection. Medical records of pediatric patients who underwent resection of IDEM tumors with the assistance of MEP between March 2011 and October 2020 were reviewed. The occurrence of postoperative motor deficits was correlated with intraoperative MEP alerts. Sixteen patients were included. MEP alerts appeared in 2 patients (12.5%), being reflective of new postoperative motor deficits. Among the remaining 14 patients without any intraoperative MEP alerts, no motor decline was found. Accordingly, MEP significantly predicted postoperative motor deficits, reaching sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100% (p < 0.001). In the absence of MEP alerts, 11 out of 14 patients (78.6%) underwent GTR, while no patient with intraoperative IONM alerts underwent GTR (p = 0.025). Although MEP alerts limit the extent of tumor resection, the high sensitivity and PPV of MEP underline its importance in avoiding iatrogenic motor deficits. Concurrently, high specificity and NPV ensure safer tumor excision. Therefore, MEP can reliably support surgical decisions in pediatric patients with IDEM tumors.
Impact of SGLT2 Inhibitor Therapy on Right Ventricular Function in Patients with Heart Failure and Reduced Ejection Fraction
Authors: Mustapic Ivona , Bakovic Darija , Susilovic Grabovac Zora , Borovac Josip A
Published: December 2022

Background: The impact of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in addition to optimal medical therapy (OMT) on the right ventricular (RV) systolic function using advanced echocardiographic analysis among outpatients with heart failure and a reduced ejection fraction (HFrEF) has thus far been poorly investigated. Methods: This was a single-center, prospective, single-blinded study in which an echocardiographic expert was blinded to the allocation of the treatment. A total of 36 outpatients with HFrEF were randomized to either OMT or OMT+SGLT2i. Both groups underwent an echocardiographic examination of the RV systolic function at the baseline and at the 3-month follow-up (3mFU). Results: The patients in both groups did not significantly differ with respect to the relevant baseline comorbidities, therapy, and clinical characteristics. The patients receiving OMT+SGLT2i showed a significant improvement from the baseline to the 3mFU in all the measured RV echocardiographic parameters, while for the OMT group, a significant improvement after the 3mFU was observed for TAPSE and s’. The mean percent change from the baseline to the 3mFU was significant when comparing OMT+SGLT2i to the OMT group concerning RV FWS (+91% vs. +28%, p = 0.039), TR maxPG (−27% vs. +19%, p = 0.005), and TR Vmax (−17% vs. +13%, p = 0.008), respectively. Conclusions: Adding SGLT2i to OMT in patients with HFrEF resulted in a greater improvement in the RV systolic function from the baseline to the 3mFU compared to the OMT alone.
Effect of Topical Prostaglandin Analogue Therapy on Central Corneal Thickness: A Systematic Review
Authors: Kim Jae-Yun , Yim Hyeon-Woo
Published: December 2022

To investigate whether prostaglandin analogue (PGA) eyedrops have a significant effect on central corneal thickness (CCT), we conducted a systematic search of literature published from 2000 to 2021. Among the studies conducted on topical PGA therapy in open-angle glaucoma or ocular hypertension patients over 18 years old, prospective studies with CCT change as an outcome were included. A single-arm meta-analysis was conducted to assess the overall effect on CCT, and subgroup analysis according to exposure time of PGA eyedrops was also performed. We counted the number of articles that reported on severe events (CCT reduction of 25 μm or more) and obtained their proportion. The methodological quality was assessed by the McHarm tool. Twenty-two reports of prospective studies were selected. The results of the single-arm meta-analysis showed very high heterogeneity. Still, in subgroup analysis, when PGA was used for more than 6 months, heterogeneity was low, and a significant decrease in CCT was observed. Severe events were reported in two reports and occurred in 3.8% to 14.8% of participants. PGA eyedrop use may cause a clinically significant CCT decrease, requiring CCT follow-up.
Dynamics Modeling and Analysis of an Underwater Glider with Dual-Eccentric Attitude Regulating Mechanism Using Dual Quaternions
Authors: Wang Peng , Wang Xuehao , Wang Yanhui , Niu Wendong , Yang Shaoqiong , Sun Chao , Luo Chenyi
Published: December 2022

The underwater glider has difficulty accessing the complex and narrow hadal trench for observation, which is affected by its limited regulation capability of pitch angle (−45°~45°). In this study, a compact attitude regulating mechanism is proposed to extend the regulation range of pitch angle from −90°to 90° and to install it on the hadal-class underwater glider Petrel-XPLUS. Subsequently, the dynamics model of Petrel-XPLUS is established using dual quaternions to solve the “gimbal lock” problem caused by the increased pitch angle range. Within the extended pitch range, the motion modes of the glider are enriched into long-range, virtual mooring, and Lagrangian float modes for long-range, small-area, and current-following observation missions, respectively, and are analyzed using the established dynamics model. Moreover, a ballast method was used to modify the pitch angle range and initial equilibrium state of a constructed underwater glider. Finally, Petrel-XPLUS achieved a pitch angle regulation range of −90°~90° in a water pool experiment and completed three consecutive profiles in a sea trial in the Challenger Deep, Mariana Trench, with all depths over 10,000 m, of which the maximum depth was 10,619 m. The proposed mechanism and methods can also be applied to other submersibles to facilitate ocean observations.
New Research Advances on Marine Invertebrates
Authors: Lobo-da-Cunha Alexandre
Published: December 2022

Marine ecosystems encompass a wide variety of invertebrates, pelagic and benthonic, from intertidal to deep-sea habitats in polar to tropical regions [...]
Complementary Strategies to Unlock Biosynthesis Gene Clusters Encoding Secondary Metabolites in the Filamentous Fungus Podospora anserina
Authors: Shen Ling , Roullier Catherine , Porée François-Hugues , Gaslonde Thomas , Riffault-Valois Ludivine , Grovel Olivier , Ruprich-Robert Gwenaël , Chapeland-Leclerc Florence
Published: December 2022

The coprophilous ascomycete Podospora anserina is known to have a high potential to synthesize a wide array of secondary metabolites (SMs). However, to date, the characterization of SMs in this species, as in other filamentous fungal species, is far less than expected by the functional prediction through genome mining, likely due to the inactivity of most SMs biosynthesis gene clusters (BGCs) under standard conditions. In this work, our main objective was to compare the global strategies usually used to deregulate SM gene clusters in P. anserina, including the variation of culture conditions and the modification of the chromatin state either by genetic manipulation or by chemical treatment, and to show the complementarity of the approaches between them. In this way, we showed that the metabolomics-driven comparative analysis unveils the unexpected diversity of metabolic changes in P. anserina and that the integrated strategies have a mutual complementary effect on the expression of the fungal metabolome. Then, our results demonstrate that metabolite production is significantly influenced by varied cultivation states and epigenetic modifications. We believe that the strategy described in this study will facilitate the discovery of fungal metabolites of interest and will improve the ability to prioritize the production of specific fungal SMs with an optimized treatment.
Strategies for Controlling the Sporulation in Fusarium spp.
Authors: Ajmal Maria , Hussain Adil , Ali Asad , Chen Hongge , Lin Hui
Published: December 2022

Fusarium species are the most destructive phytopathogenic and toxin-producing fungi, causing serious diseases in almost all economically important plants. Sporulation is an essential part of the life cycle of Fusarium. Fusarium most frequently produces three different types of asexual spores, i.e., macroconidia, chlamydospores, and microconidia. It also produces meiotic spores, but fewer than 20% of Fusaria have a known sexual cycle. Therefore, the asexual spores of the Fusarium species play an important role in their propagation and infection. This review places special emphasis on current developments in artificial anti-sporulation techniques as well as features of Fusarium’s asexual sporulation regulation, such as temperature, light, pH, host tissue, and nutrients. This description of sporulation regulation aspects and artificial anti-sporulation strategies will help to shed light on the ways to effectively control Fusarium diseases by inhibiting the production of spores, which eventually improves the production of food plants.
A Comparative Analysis of Anticardiolipin, Anti-Β2-Glycoprotein-1, and Lupus Anticoagulants in Saudi Women with Recurrent Spontaneous Abortions
Authors: Shaikhomar Osama Abdulrahman , Ali Syed Tabrez
Published: December 2022

Association and pathogenesis of antiphospholipid antibodies (APAs) in patients with Antiphospholipid syndrome (APS) as well as systemic lupus erythematosus (SLE) suffering from unexplained spontaneous abortions is controversial. Moreover, the majority of the published evidence is based on the patient histories rather than the study groups. The main objective of the present study is to do a comparative analysis of the high levels of antiphospholipid antibodies (APAs) including anticardiolipin (ACA), anti-β2-glycoprotein-1 (β2 GP1), and Lupus anticoagulants (LA) and their association with the gestational age of abortion and duration past abortion in Saudi women. In this study, 100 women living in Makkah city, located in the Western region of Saudi Arabia, with a mean age of 30.5 ± 12.60 years (mean ± standard deviation), having a previous history of recurrent spontaneous abortions were enrolled as case group and 100 healthy pregnant women previously having one or more successful pregnancies were selected as control group. Based on the gestational age of the patient’s miscarriages, our results revealed consistently and significantly high levels of ACA, β2 GP1, and LA, being greatest at more than 15 weeks when compared with 10 weeks and 11–15 weeks, respectively. Based on duration of past miscarriages, a slightly increased level was observed at ≤4 years after their first miscarriage. In addition, less or more equal levels of these antibodies were observed at 5–12 and more than 12 years in all the cases of miscarriages. We concluded an elevated pattern of APAs in these patients with an increase in the age of abortion. A comparison between the levels of ACA, β2 GP1, and LA further indicated a highly significant level of LA in all the cases of abortions (p < 0.0005).
Asymmetric Information Flow between Exchange Rate, Oil, and Gold: New Evidence from Transfer Entropy Approach
Authors: Maiti Moinak , Kayal Parthajit
Published: December 2022

The present study used transfer entropy and effective transfer entropy to examine the asymmetric information flow between exchange rates, oil, and gold. The dataset is composed of daily data covering the period of 1 January 2018 to 31 December 2021. Further, the dataset is bifurcated for analysis for before and during COVID. The bidirectional information flow is observed between EUR/USD and Oil for the whole study period unlike before COVID. However, during COVID, there was a unidirectional information flow from Oil→EUR/USD. The study finds a significant unidirectional information flow from Gold→EUR/USD. The study estimates also indicate that before COVID, the direction of information flow was from Oil→Gold. However, the direction of information flow reversed during COVID from Gold→Oil. Overall, the direction of information flow among these three variables is asymmetric. The highest transfer entropy was observed for Gold→EUR/USD among all the pairs under consideration.
Portfolio Diversification, Hedge and Safe-Haven Properties in Cryptocurrency Investments and Financial Economics: A Systematic Literature Review
Authors: Almeida José , Gonçalves Tiago Cruz
Published: December 2022

Our study collected and synthetized the existing knowledge on portfolio diversification, hedge, and safe-haven properties in cryptocurrency investments. We sampled 146 studies published in journals ranked in the Association of Business Schools 2021 journals list, considering all fields of knowledge, and elaborated a systematic literature review along with a bibliometric analysis. Our results indicate a fast-growing literature evidencing cryptocurrencies’ ability to hedge against stocks, fiat currencies, geopolitical risks, and Economic Policy Uncertainty (EPU) risk; also, that cryptocurrencies present diversification and safe-haven properties; that stablecoins reveal unstable peg with the US dollar; that uncertainty is a determinant for cryptocurrency returns. Additionally, we show that investors should consider Gold, along with the European carbon market, CBOE Bitcoin futures, and crude oil to hedge against unexpected movements in the cryptocurrency market.
The Writ of Amparo and Indigenous Consultation as Instruments to Enforce Inclusive Land Management in San Andrés Cholula, Mexico
Authors: Schumacher Melissa , Guizar Villalvazo María , Kurjenoja Anne Kristiina , Durán-Díaz Pamela
Published: December 2022

In 2019, residents of the rural district of San Rafael Comac in the municipality of San Andrés Cholula, Mexico, challenged the implementation of the 2018 Municipal Program for Sustainable Urban Development of San Andrés Cholula (MPSUD), a rapacious urban-planning policy that was negatively affecting ancestral communities—pueblos originarios—and their lands and traditions. In 2020, a legal instrument called the writ of amparo was proven effective in ordering the repeal of the MPSUD and demanding an Indigenous consultation, based on the argument of self-recognition of local and Indigenous identity. Such identity would grant them the specific land rights contained in the Mexican Constitution and in international treaties. To explain their Indigenous identity in the writ of amparo, they referred to an established ancient socio-spatial system of organization that functioned beyond administrative boundaries: the Mesoamerican altepetl system. The altepetl, consisting of the union between land and people, is appointed in the writ of amparo as the foundation of their current form of socio-spatial organization. This paper is a land-policy review of the MPSUD and the writ of amparo, with a case-study approach for San Rafael Comac, based on a literature review. The research concludes that Indigenous consultation is a key tool and action for empowerment towards responsible land-management in a context where private urban-development impinges on traditional land uses and customs, and could be beneficial for traditional communities in Mexico and other Latin American countries.
High-Speed Railway Opening and Urban Innovation Dividend—A Case Study of Guangzhou Zhuhai Intercity High-Speed Railway
Authors: Cheng Shuping , Liu Jinli , Xu Jingxue , Qiu Yumin
Published: December 2022

Based on the panel data of 41 cities along and around the Guangzhou Zhuhai intercity railway (GZR) from 2005 to 2018 and taking the opening of the GZR as a natural experimental scenario, the difference-in-difference (DID) method was used to empirically test the impact of the opening of the GZR on the innovation of cities along the line. The research results show that the opening of GZR has had a statistically positive effect on the innovation of cities along the route—that is, the innovation dividend of high-speed railway (HSR)cities exists, which improves the level of urban innovation—and further, there is time dynamics and regional heterogeneity in the innovation dividend. The research results of this paper have significant policy implications for optimizing China’s HSR network.
Expression Profile of Hydroxysteroid Dehydrogenase-like 2 in Polychaete Perinereis aibuhitensis in Response to BPA
Authors: Li Yingpeng , Zhao Huan , Pang Min , Huang Yi , Zhang Boxu , Yang Dazuo , Zhou Yibing
Published: December 2022

Hydroxysteroid dehydrogenases (HSDs) play an important role in the metabolism of steroids and xenobiotics. However, the function of HSDs in invertebrates is unclear. In this study, we cloned the hydroxysteroid dehydrogenase-like 2 (HSDL2) gene in Perinereis aibuhitensis, which is 1652 bp in length, encoding 400 amino acids. This sequence contains conserved short-chain dehydrogenase and sterol carrier protein-2 domain, and the alignment analysis showed its close relationship with other invertebrate HSDL2. Further, the tissue distribution analysis of the HSDL2 gene showed it is expressed strongly in the intestine. The expression level of HSDL2 after inducement with bisphenol A (BPA) was also detected both at transcriptional and translational levels. The results inferred that BPA exposure can induce HSDL2 expression, and the inductive effect was obvious in the high-concentration BPA group (100 μg/L). In summary, our results showed the detoxification function of HSDL2 in polychaetes.