bluuebunny/crossref_metadata_2025 huggingface dataset:
Human RNASET2: A Highly Pleiotropic and Evolutionary Conserved Tumor Suppressor Gene Involved in the Control of Ovarian Cancer Pathogenesis
Authors: Bruno Antonino , Noonan Douglas M. , Valli Roberto , Porta Giovanni , Taramelli Roberto , Mortara Lorenzo , Acquati Francesco
Published: August 2022

Ovarian cancer represents one of the most malignant gynecological cancers worldwide, with an overall 5-year survival rate, being locked in the 25–30% range in the last decade. Cancer immunotherapy is currently one of the most intensively investigated and promising therapeutic strategy and as such, is expected to provide in the incoming years significant benefits for ovarian cancer treatment as well. Here, we provide a detailed survey on the highly pleiotropic oncosuppressive roles played by the human RNASET2 gene, whose protein product has been consistently reported to establish a functional crosstalk between ovarian cancer cells and key cellular effectors of the innate immune system (the monocyte/macrophages lineage), which is in turn able to promote the recruitment to the cancer tissue of M1-polarized, antitumoral macrophages. This feature, coupled with the ability of T2 ribonucleases to negatively affect several cancer-related parameters in a cell-autonomous manner on a wide range of ovarian cancer experimental models, makes human RNASET2 a very promising candidate to develop a “multitasking” therapeutic approach for innovative future applications for ovarian cancer treatment.
Experimental Evidence for the Anti-Metastatic Action of Ginsenoside Rg3: A Systematic Review
Authors: Oh Hyeon-Muk , Cho Chong-Kwan , Son Chang-Gue
Published: August 2022

Cancer metastasis is the leading cause of death in cancer patients. Due to the limitations of conventional cancer treatment, such as chemotherapy, there is a need for novel therapeutics to prevent metastasis. Ginsenoside Rg3, a major active component of Panax ginseng C.A. Meyer, inhibits tumor growth and has the potential to prevent tumor metastasis. Herein, we systematically reviewed the anti-metastatic effects of Rg3 from experimental studies. We searched for articles in three research databases, MEDLINE (PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) through March 2022. In total, 14 studies (eight animal and six in vitro) provide data on the anti-metastatic effects of Rg3 and the relevant mechanisms. The major anti-metastatic mechanisms of Rg3 involve cancer stemness, epithelial mesenchymal transition (EMT) behavior, and angiogenesis. Taken together, Rg3 would be one of the herbal resources in anti-metastatic drug developments through further well-designed investigations and clinical studies. Our review provides valuable reference data for Rg3-derived studies targeting tumor metastasis.
Tumor Necrosis Factor-α-Induced C-C Motif Chemokine Ligand 20 Expression through TNF Receptor 1-Dependent Activation of EGFR/p38 MAPK and JNK1/2/FoxO1 or the NF-κB Pathway in Human Cardiac Fibroblasts
Authors: Yang Chuen-Mao , Yang Chien-Chung , Hsu Wun-Hsin , Hsiao Li-Der , Tseng Hui-Ching , Shih Ya-Fang
Published: August 2022

Tumor necrosis factor (TNF)-α is involved in the pathogenesis of cardiac injury, inflammation, and apoptosis. It is a crucial pro-inflammatory cytokine in many heart disorders, including chronic heart failure and ischemic heart disease, contributing to cardiac remodeling and dysfunction. The implication of TNF-α in inflammatory responses in the heart has been indicated to be mediated through the induction of C-C Motif Chemokine Ligand 20 (CCL20). However, the detailed mechanisms of TNF-α-induced CCL20 upregulation in human cardiac fibroblasts (HCFs) are not completely defined. We demonstrated that in HCFs, TNF-α induced CCL20 mRNA expression and promoter activity leading to an increase in the secretion of CCL20. TNF-α-mediated responses were attenuated by pretreatment with TNFR1 antibody, the inhibitor of epidermal growth factor receptor (EGFR) (AG1478), p38 mitogen-activated protein kinase (MAPK) (p38 inhibitor VIII, p38i VIII), c-Jun amino N-terminal kinase (JNK)1/2 (SP600125), nuclear factor kappaB (NF-κB) (helenalin), or forkhead box O (FoxO)1 (AS1841856) and transfection with siRNA of TNFR1, EGFR, p38α, JNK2, p65, or FoxO1. Moreover, TNF-α markedly induced EGFR, p38 MAPK, JNK1/2, FoxO1, and NF-κB p65 phosphorylation which was inhibited by their respective inhibitors in these cells. In addition, TNF-α-enhanced binding of FoxO1 or p65 to the CCL20 promoter was inhibited by p38i VIII, SP600125, and AS1841856, or helenalin, respectively. Accordingly, in HCFs, our findings are the first to clarify that TNF-α-induced CCL20 secretion is mediated through a TNFR1-dependent EGFR/p38 MAPK and JNK1/2/FoxO1 or NF-κB cascade. We demonstrated that TNFR1-derived EGFR transactivation is involved in the TNF-α-induced responses in these cells. Understanding the regulation of CCL20 expression by TNF-α on HCFs may provide a potential therapeutic strategy in cardiac inflammatory disorders.
UDP-Glucose: A Cereblon-Dependent Glucokinase Protein Degrader
Authors: Cho Jaeyong , Miyagawa Atsushi , Yamaguchi Kazuki , Abe Wakana , Tsugawa Yoji , Yamamura Hatsuo , Imai Takeshi
Published: August 2022

We previously reported that glucokinase is ubiquitinated and degraded by cereblon with an unknown endogenous glucokinase protein degrader. Here, we show that UDP-glucose is a glucokinase protein degrader. We identified that both glucose and UDP-glucose bind to glucokinase and that both uridine and UDP-glucose bind to cereblon in a similar way to thalidomide. From these results, UDP-glucose was identified as a molecular glue between cereblon and glucokinase. Glucokinase produces glucose-6-phosphate in the pancreas and liver. Especially in β-cells, glucokinase is the main target of glucose for glucose-induced insulin secretion. UDP-glucose administration ubiquitinated and degraded glucokinase, lowered glucose-6-phosphate production, and then reduced insulin secretion in β-cell lines and mice. Maturity-onset diabetes of the young type 2 (MODY2) glucokinaseE256K mutant protein was resistant to UDP-glucose induced ubiquitination and degradation. Taken together, glucokinase ubiquitination and degradation signaling might be impaired in MODY2 patients.
Controllable Nitric Oxide Storage and Release in Cu-BTC: Crystallographic Insights and Bioactivity
Authors: Lee Do Nam , Kim Yeong Rim , Yang Sohyeon , Tran Ngoc Minh , Park Bong Joo , Lee Su Jung , Kim Youngmee , Yoo Hyojong , Kim Sung-Jin , Shin Jae Ho
Published: August 2022

Crystalline metal–organic frameworks (MOFs) are extensively used in areas such as gas storage and small-molecule drug delivery. Although Cu-BTC (1, MOF-199, BTC: benzene-1,3,5-tricarboxylate) has versatile applications, its NO storage and release characteristics are not amenable to therapeutic usage. In this work, micro-sized Cu-BTC was prepared solvothermally and then processed by ball-milling to prepare nano-sized Cu-BTC (2). The NO storage and release properties of the micro- and nano-sized Cu-BTC MOFs were morphology dependent. Control of the hydration degree and morphology of the NO delivery vehicle improved the NO release characteristics significantly. In particular, the nano-sized NO-loaded Cu-BTC (NO⊂nano-Cu-BTC, 4) released NO at 1.81 µmol·mg−1 in 1.2 h in PBS, which meets the requirements for clinical usage. The solid-state structural formula of NO⊂Cu-BTC was successfully determined to be [CuC6H2O5]·(NO)0.167 through single-crystal X-ray diffraction, suggesting no structural changes in Cu-BTC upon the intercalation of 0.167 equivalents of NO within the pores of Cu-BTC after NO loading. The structure of Cu-BTC was also stably maintained after NO release. NO⊂Cu-BTC exhibited significant antibacterial activity against six bacterial strains, including Gram-negative and positive bacteria. NO⊂Cu-BTC could be utilized as a hybrid NO donor to explore the synergistic effects of the known antibacterial properties of Cu-BTC.
Melatonin Regulates the Daily Levels of Plasma Amino Acids, Acylcarnitines, Biogenic Amines, Sphingomyelins, and Hexoses in a Xenograft Model of Triple Negative Breast Cancer
Authors: Junior Rubens Paula , Chuffa Luiz Gustavo de Almeida , Simão Vinicius Augusto , Sonehara Nathália Martins , Chammas Roger , Reiter Russel J. , Zuccari Debora Aparecida Pires de Campos
Published: August 2022

Metabolic dysregulation as a reflection of specific metabolite production and its utilization is a common feature of many human neoplasms. Melatonin, an indoleamine that is highly available during darkness, has a variety of metabolic functions in solid tumors. Because plasma metabolites undergo circadian changes, we investigated the role of melatonin on the profile of amino acids (AAs), biogenic amines, carnitines, sphingolipids, and hexoses present in the plasma of mice bearing xenograft triple negative breast cancer (MDA-MB-231 cells) over 24 h. Plasma concentrations of nine AAs were reduced by melatonin, especially during the light phase, with a profile closer to that of non-breast cancer (BC) animals. With respect to acylcarnitine levels, melatonin reduced 12 out of 24 molecules in BC-bearing animals compared to their controls, especially at 06:00 h and 15:00 h. Importantly, melatonin reduced the concentrations of asymmetric dimethylarginine, carnosine, histamine, kynurenine, methionine sulfoxide, putrescine, spermidine, spermine, and symmetric dimethylarginine, which are associated with the BC metabolite sets. Melatonin also led to reduced levels of sphingomyelins and hexoses, which showed distinct daily variations over 24 h. These results highlight the role of melatonin in controlling the levels of plasma metabolites in human BC xenografts, which may impact cancer bioenergetics, in addition to emphasizing the need for a more accurate examination of its metabolomic changes at different time points.
Aortic Arch Phenotypes in Double Outlet Right Ventricle (DORV)—Implications for Surgery and Multi-Modal Imaging
Authors: Gressani Alessandro , Aynetdinova Renata , Kostolny Martin , Schievano Silvia , Cook Andrew , Belitsis Georgios
Published: August 2022

Abnormal aortic arches (AAAs) cover a spectrum of malformations, including abnormal laterality, branching patterns, and flow-limiting narrowing, which themselves vary from tubular hypoplasia, through discrete coarctation, to complete interruption of the arch. Neonatal surgery within the first days of life is necessary for most of these morphologies. Patch aortoplasty is widely used as it can offer a good haemodynamic result, being tailored to each combination of presenting pathologies. Our study hypothesis was that arch malformations are frequent in DORV and exhibit a plethora of phenotypes. We reviewed 54 post-mortem heart specimens from the UCL Cardiac Archive, analysing morphological features that would potentially influence the surgical repair, and taking relevant measurements of surgical importance. AAAs were found in half of the specimens, including 22.2% with aortic arch narrowing. In total, 70% and 30% of narrow arches had a subpulmonary and subaortic interventricular defect, respectively. Z-scores were significantly negative for all cases with tubular hypoplasia. We concluded that arch malformations are a common finding among hearts with DORV. Surgery on the neonatal aortic arch in DORV, performed in conjunction with other interventions that aim to balance pulmonary to systemic flow (Qp/Qs), should be anticipated and form an important part of multi-modal imaging.
A Prospective Analysis of Skin and Fingertip Advanced Glycation End-Product Devices in Healthy Volunteers
Authors: Adl Amini Dominik , Moser Manuel , Chiapparelli Erika , Oezel Lisa , Zhu Jiaqi , Okano Ichiro , Shue Jennifer , Sama Andrew A. , Cammisa Frank P. , Girardi Federico P. , Hughes Alexander P.
Published: August 2022

Background: Advanced glycation end products (AGEs) have been shown to accumulate in bone and are gaining interest in connective tissue research. Aims: To investigate the intrarater reliability, two-timepoint agreement and correlations within and between two commercially available skin autofluorescence (SAF) AGE devices. Methods: Healthy volunteers were enrolled in a prospective study at a single academic institution. Each participant underwent SAF analysis by two different, commercially available devices on two occasions, 14 days apart. Upon enrollment, a general survey about the participant’s lifestyle and health status was completed and followed up on for any changes at timepoint two. Results: In total, 40 participants (F:M ratio 5:3) with an average age of 39.0 ± 12.5 years were analyzed. For the AGE reader (skin) and AGE sensor (fingertip), both intrarater reliability and two-timepoint agreement were excellent with an interclass correlation coefficient (ICC) > 0.90 and a strong correlation within both machines. However, there was no correlation between both machines for either timepoint. In total, 4 participants were identified as outliers above the +2SD. Additionally, 5 participants with dark-colored skin could not be measured with the AGE reader at timepoint one and 4 at timepoint two. In contrast, all participants were able to undergo SAF analysis with the AGE sensor, irrespective of their skin type. Conclusions: Both machines showed excellent intrarater reliability and two-timepoint agreement, but the skin AGE reader might have limited applicability in individuals with dark-colored skin. Future research on AGEs might take our findings into consideration.
The Profile of Markers of Bone Turnover, Inflammation and Extracellular Neutrophil Traps on Bone Mass in Haemophilia and the Development of Haemophilic Arthropathy
Authors: Czajkowska Sylwia , Rupa-Matysek Joanna , Wojtasińska Ewelina , Nijakowski Kacper , Surdacka Anna , Gil Lidia
Published: August 2022

Background: The aim of the study is to evaluate selected biomarkers of bone turnover, inflammation, neutrophil trap and factors predisposing haemophiliacs to bone loss, and to analyse their relationship with clinical features, treatment and complications. Methods: The levels of interleukin 6 (IL-6); citrullinated histone (CH3); osteocalcin (BGLAP); bone alkaline phosphatase (BALP); N-terminal procollagen type I propeptide (P1NP); and C-terminal collagen type I telopeptide (C1CP) were examined in 60 patients with haemophilia. Results: The cut-off value for BGLAP is 26.41 ng/mL, and 929.7 pg/mL for CH3. There is a statistically significant difference between BGLAP, BALP, C1CP and CH3 concentrations, depending on the prophylaxis used. The median concentration of BGLAP in patients taking the factor on demand is 28.0 ng/mL, BALP 322.5 U/L, C1CP 191.2 ng/mL and CH3 1114.4 pg/mL. In patients taking recombinant coagulation factor VIII/IX as prophylaxis of bleeding, the median BGLAP concentrations are 35.9 ng/mL, BALP 280.9 U/L, C1CP 161.6 ng/mL and CH3 952.5 pg/mL. BGLAP and BALP concentrations are dependent on the development of haemophilic arthropathic. Conclusions: The concentrations of selected markers of bone turnover and NETs may help to identify patients at particular risk of developing haemophilic arthropathy and bone metabolic turnover abnormalities.
Current Options and Future Perspectives in the Treatment of Dyslipidemia
Authors: Muscoli Saverio , Ifrim Mihaela , Russo Massimo , Candido Francesco , Sanseviero Angela , Milite Marialucia , Di Luozzo Marco , Marchei Massimo , Sangiorgi Giuseppe
Published: August 2022

Low-density lipoprotein cholesterol (LDL-C) plays a crucial role in the development of atherosclerosis. Statin therapy is the standard treatment for lowering LDL-C in primary and secondary prevention. However, some patients do not reach optimal LDL-C target levels or do not tolerate statins, especially when taking high doses long-term. Combining statins with different therapeutic approaches and testing other new drugs is the future key to reducing the burden of cardiovascular disease (CVD). Recently, several new cholesterol-lowering drugs have been developed and approved; others are promising results, enriching the pharmacological armamentarium beyond statins. Triglycerides also play an important role in the development of CVD; new therapeutic approaches are also very promising for their treatment. Familial hypercholesterolemia (FH) can lead to CVD early in life. These patients respond poorly to conventional therapies. Recently, however, new and promising pharmacological strategies have become available. This narrative review provides an overview of the new drugs for the treatment of dyslipidemia, their current status, ongoing clinical or preclinical trials, and their prospects. We also discuss the new alternative therapies for the treatment of dyslipidemia and their relevance to practice.
The Role and Implications of Epicardial Fat in Coronary Atherosclerotic Disease
Authors: Braescu Laurentiu , Gaspar Marinica , Buriman Darius , Aburel Oana Maria , Merce Adrian-Petru , Bratosin Felix , Aleksandrovich Klokov Sergei , Alambaram Satish , Mornos Cristian
Published: August 2022

The current minireview aims to assess the implications of epicardial fat secretory function in the development of coronary artery disease. The epicardial adipose tissue (EAT) is a visceral fat depot that has been described as a cardiovascular risk factor. In addition to its mechanical protection role and physiological secretory function, it seems that various secretion products of the epicardial fat are responsible for metabolic disturbances at the level of the cardiac muscle when in association with pre-existing pathological conditions, such as metabolic syndrome. There is a pathological reduction in sarcomere shortening, abnormal cytosolic Ca2+ fluxes, reduced expression of sarcoplasmic endoplasmic reticulum ATPase 2a and decreased insulin-mediated Akt-Ser473-phosphorylation in association with abnormal levels of epicardial fat tissue. Activin A, angiopoietin-2, and CD14-positive monocytes selectively accumulate in the diseased myocardium, resulting in reduced cardiomyocyte contractile function. At the same time, it is believed that these alterations in secretory products directly decrease the myocyte function via molecular changes, thus contributing to the development of coronary disease when certain comorbidities are associated.
Early Adverse Events and Immune Response Following Second and Third COVID-19 Vaccination in Pregnancy
Authors: Toussia-Cohen Shlomi , Yinon Yoav , Peretz-Machluf Ravit , Segal Omri , Regev Noam , Asraf Keren , Doolman Ram , Kubani Yonatan , Gonen Tal , Regev-Yochay Gili , Bookstein Peretz Shiran
Published: August 2022

(1) Background: The adverse-effect profile and short-term obstetric and neonatal outcomes among pregnant women who were vaccinated with the BNT162b2 vaccine at any stage of pregnancy do not indicate any safety concerns. The vaccine is effective in generating a humoral immune response in pregnant women. (2) Objective: To determine the vaccine-induced immunity and adverse events associated with the third (booster) dose of the BNT162b2 vaccine compared to the first and second dose of the vaccine among pregnant women. (3) Study design: A prospective cohort study in a tertiary referral center comparing pregnant women who were vaccinated by the first and second dose of the BNT162b2 (Pfizer/BioNTech) vaccine to pregnant women vaccinated by a third (booster) dose, between January and November 2021. A digital questionnaire regarding adverse events was filled by both groups 2–4 weeks after vaccination. Blood samples were collected and tested for SARS-COV-2 IgG antibodies 28–32 days after the administration of the second or third BNT162b2 dose. (4) Results: Seventy-eight pregnant women who received the first and second doses of the vaccine were compared to eighty-four pregnant women who received the third dose of the vaccine. In terms of adverse events following vaccination, local rash/pain/swelling (93.6% vs. 72.6%, p < 0.001) was significantly less common after the third vaccination compared to after the second vaccination. Other adverse events, including early obstetric complications, did not differ between the two groups. SARS-CoV-2 IgG serum levels 28–32 days after the vaccination were significantly higher after the third vaccination compared to the second vaccination (1333.75 vs. 2177.93, respectively, p < 0.001). (5) Conclusion: This study confirms the safety regarding early adverse events and immunogenicity, and the lack of early obstetric complications of the BNT162b2 second- and third-dose vaccine in pregnant women. The third (booster) dose is effective in generating a stronger humoral immune response in pregnant women compared with the second dose.
Application of Machine Learning in Hospitalized Patients with Severe COVID-19 Treated with Tocilizumab
Authors: Ramón Antonio , Zaragozá Marta , Torres Ana María , Cascón Joaquín , Blasco Pilar , Milara Javier , Mateo Jorge
Published: August 2022

Among the IL-6 inhibitors, tocilizumab is the most widely used therapeutic option in patients with SARS-CoV-2-associated severe respiratory failure (SRF). The aim of our study was to provide evidence on predictors of poor outcome in patients with COVID-19 treated with tocilizumab, using machine learning (ML) techniques. We conducted a retrospective study, analyzing the clinical, laboratory and sociodemographic data of patients admitted for severe COVID-19 with SRF, treated with tocilizumab. The extreme gradient boost (XGB) method had the highest balanced accuracy (93.16%). The factors associated with a worse outcome of tocilizumab use in terms of mortality were: baseline situation at the start of tocilizumab treatment requiring invasive mechanical ventilation (IMV), elevated ferritin, lactate dehydrogenase (LDH) and glutamate-pyruvate transaminase (GPT), lymphopenia, and low PaFi [ratio between arterial oxygen pressure and inspired oxygen fraction (PaO2/FiO2)] values. The factors associated with a worse outcome of tocilizumab use in terms of hospital stay were: baseline situation at the start of tocilizumab treatment requiring IMV or supplemental oxygen, elevated levels of ferritin, glutamate-oxaloacetate transaminase (GOT), GPT, C-reactive protein (CRP), LDH, lymphopenia, and low PaFi values. In our study focused on patients with severe COVID-19 treated with tocilizumab, the factors that were weighted most strongly in predicting worse clinical outcome were baseline status at the start of tocilizumab treatment requiring IMV and hyperferritinemia.
The Use of 3D-Printed Custom-Made Implants as an Attractive Potential Alternative to the Treatment of Segmental Bone Loss in Foot and Ankle
Authors: Caravelli Silvio , Ambrosino Giuseppe , Grassi Alberto , Zaffagnini Stefano , Mosca Massimiliano
Published: August 2022

The treatment of segmental tibial and ankle bone loss after radical surgery for chronic osteomyelitis is one of the most challenging problems encountered by orthopaedic surgeons [...]
A Study on the Pathogenesis of Vascular Cognitive Impairment and Dementia: The Chronic Cerebral Hypoperfusion Hypothesis
Authors: Yu Weiwei , Li Yao , Hu Jun , Wu Jun , Huang Yining
Published: August 2022

The pathogenic mechanisms underlying vascular cognitive impairment and dementia (VCID) remain controversial due to the heterogeneity of vascular causes and complexity of disease neuropathology. However, one common feature shared among all these vascular causes is cerebral blood flow (CBF) dysregulation, and chronic cerebral hypoperfusion (CCH) is the universal consequence of CBF dysregulation, which subsequently results in an insufficient blood supply to the brain, ultimately contributing to VCID. The purpose of this comprehensive review is to emphasize the important contributions of CCH to VCID and illustrate the current findings about the mechanisms involved in CCH-induced VCID pathological changes. Specifically, evidence is mainly provided to support the molecular mechanisms, including Aβ accumulation, inflammation, oxidative stress, blood-brain barrier (BBB) disruption, trophic uncoupling and white matter lesions (WMLs). Notably, there are close interactions among these multiple mechanisms, and further research is necessary to elucidate the hitherto unsolved questions regarding these interactions. An enhanced understanding of the pathological features in preclinical models could provide a theoretical basis, ultimately achieving the shift from treatment to prevention.
Real-Time Weight Optimization of a Nonlinear Model Predictive Controller Using a Genetic Algorithm for Ship Trajectory Tracking
Authors: Yu Dunjing , Deng Fang , Wang Hongyan , Hou Xiuhui , Yang Hualin , Shan Tikun
Published: August 2022

This paper presents a weight optimization method for a nonlinear model predictive controller (NMPC) based on the genetic algorithm (GA) for ship trajectory tracking. The weight coefficients Q and R of the objective function in NMPC are obtained via the real-time optimization of the genetic algorithm instead of the trial and error method, which improves the efficiency and accuracy of the controller. In addition, targeted improvements are made to the internal crossover operator, mutation operator, crossover rate, and mutation rate of the genetic algorithm. The simulation comparison of trajectory tracking between NMPC with real-time-optimized weight coefficients and the one with constant coefficients is performed. Finally, the simulation result shows that the controller with real-time-optimized weight coefficients has a better trajectory tracking effect than that with constant weight coefficients.
Novel Freshwater Ascomycetes from Spain
Authors: Magaña-Dueñas Viridiana , Cano-Lira José Francisco , Stchigel Alberto Miguel
Published: August 2022

Freshwater ascomycetes are a group of fungi of great ecological importance because they are involved in decomposition processes and the recycling of organic matter in aquatic ecosystems. The taxonomy of these fungi is complex, with representatives in several orders of the phylum Ascomycota. In the present study, we collected ninety-two samples of plant debris submerged in freshwater in different locations in Spain. The plant specimens were placed in wet chambers and developed several fungi that were later isolated in pure culture. A main phylogenetic tree using the nucleotide sequences of D1–D2 domains of the 28S nrRNA gene (LSU) was built to show the taxonomic placement of all our fungal strains, and, later, individual phylogenies for the different families were built using single or concatenated nucleotide sequences of the most suitable molecular markers. As a result, we found a new species of Amniculicola that produces a coelomycetous asexual state, a new species of Elongatopedicellata that produces an asexual state, a new species of Neovaginatispora that forms both sexual and asexual states in vitro, and the sexual states of two species of Pyrenochaetopsis, none of which have been reported before for these genera. In addition, we describe a new species of Pilidium characterized by the production of copper-colored globose conidiomata, and of Pseudosigmoidea, which produces well-developed conidiophores.
Nanomedicine in Cancer Targeting and Therapy
Authors: Palamà Ilaria Elena , Leporatti Stefano
Published: August 2022

Currently, cancer represents a major cause of death in the world, despite all the progress made in developing new therapies [...]
A Mixed-Methods Protocol to Identify Best Practices for Implementing Pharmacogenetic Testing in Clinical Settings
Authors: Sperber Nina R. , Cragun Deborah , Roberts Megan C. , Bendz Lisa M. , Ince Parker , Gonzales Sarah , Haga Susanne B. , Wu R. Ryanne , Petry Natasha J. , Ramsey Laura , Uber Ryley
Published: August 2022

Using a patient’s genetic information to inform medication prescriptions can be clinically effective; however, the practice has not been widely implemented. Health systems need guidance on how to engage with providers to improve pharmacogenetic test utilization. Approaches from the field of implementation science may shed light on the complex factors affecting pharmacogenetic test use in real-world settings and areas to target to improve utilization. This paper presents an approach to studying the application of precision medicine that utilizes mixed qualitative and quantitative methods and implementation science frameworks to understand which factors or combinations consistently account for high versus low utilization of pharmocogenetic testing. This approach involves two phases: (1) collection of qualitative and quantitative data from providers—the cases—at four clinical institutions about their experiences with, and utilization of, pharmacogenetic testing to identify salient factors; and (2) analysis using a Configurational Comparative Method (CCM), using a mathematical algorithm to identify the minimally necessary and sufficient factors that distinguish providers who have higher utilization from those with low utilization. Advantages of this approach are that it can be used for small to moderate sample sizes, and it accounts for conditions found in real-world settings by demonstrating how they coincide to affect utilization.
Self-Reported Measures of Periodontitis in a Portuguese Population: A Validation Study
Authors: Machado Vanessa , Lyra Patrícia , Santos Catarina , Proença Luís , Mendes José João , Botelho João
Published: August 2022

Self-reported questionnaires have been developed and validated in multiple populations as useful tools to estimate the prevalence of periodontitis in epidemiological settings. This study aimed to explore the accuracy of self-reporting for predicting the prevalence of periodontitis in a Portuguese population. The questionnaires were given to patients at a university clinic. Thirteen self-reported questions on periodontal health were gathered in a patient-reported questionnaire. Then, self-reporting responses were validated using full-mouth periodontal examination as a comparison. Multivariable logistic regression was used to analyze sensitivity, specificity, accuracy, precision, and area under the curve-receiver operator characteristic (AUC-ROC). Self-reported answers from 103 participants (58 females and 45 males) were included. Self-reported gum health, loose teeth, tooth appearance, and use of dental floss were associated with different definitions of severe periodontitis. The self-reported questions on “having gum disease,” combined with “having gum treatment” and “having lost bone” were the items with higher performance for the 2018 case definition and the 2012 case definition, as well as for each respective severity staging. Categorization of tooth loss was only valuable for the prediction of periodontitis cases according to the 2012 case definition and its severe stage. Multiple self-reporting set-ups showed elevated performance levels for predicting periodontitis in Portuguese patients. These results may pave the way for future epidemiological surveillance programs using self-reporting approaches.
Identifying Primary Drivers of Participants from Various Socioeconomic Backgrounds to Choose National Forest Lands in the Southeastern Region of the US as a Travel Destination for Recreation
Authors: Jean Rosny , Naka Kozma , Christian Colmore S. , Gyawali Buddhi Raj , Bowman Troy , Hopkinson Sampson
Published: August 2022

Growing demand for National Forests (NFs) recreational activities makes it crucial to understand the attitudes towards valuing public recreational resources and the potential conflicts with other functions of the forests. The study was conducted to identify the primary drivers influencing individual participation in outdoor recreation on NF lands in the southeastern region of the US among participants of various socioeconomic backgrounds. The study was based on the 2010–2014 dataset of fourteen NFs across thirteen states in the Southeastern USA—retrieved from the United States Department of Agriculture (USDA). Different statistical models and statistical analyses were utilized for the study. The statistical results revealed that individual needs for relaxation were the main driver for participation in forest recreation for the whole sample and pulled data (approximately 52% of the participants). It has been noted that the drivers varied depending on the forest. The personal need for mental development was the least valued driver with only 2%. Some significant differences were observed by gender, age category, and income level. The study results have practical importance for different stakeholders such as tourism operators, the USDA Forest Service, and local authorities.
Spatial-Temporal Effect of Sea–Land Gradient on Land Use Change in Coastal Zone: A Case Study of Dalian City
Authors: Han Ying , Zhu Jianfeng , Wei Donglan , Wang Fangxiong
Published: August 2022

Geographically, the coastal zone is a unit where the marine system and the terrestrial system intersect and have the closest relationship with human survival and development. The study of coastal-zone land use change is therefore of great significance in promoting the sustainable development of coastal areas in terms of resources and environment. However, the relationship between urban land use change and distance from the coastline is indeterminate in current research. This paper aims to assess the spatial and temporal characteristics of coastal land use change with the sea–land gradient, as well as to reveal the role of coastal ecosystems. The indices of the dynamic index, net transfer matrix, and aggregation index were measured in different coastal buffer zones quantitatively. A case study of Dalian between 2000 and 2015 indicates that Dalian’s urban construction land is distributed among the coastal zones with a high total and fast growth rate. The land use conversion direction varies significantly between different buffer zones, with [0, 2.5] km tilted mainly towards urban types and [10, Max] km tilted mainly towards rural areas. The aggregation of land use structure in Dalian fluctuated and increased year by year. As the distance from the coastline gets closer, land use is going to get more diverse.
Quantitative Analysis of Spatial–Temporal Differentiation of Rural Settlements Extinction in Mountainous Areas Based on Reclamation Projects: A Case Study of Chongqing, China
Authors: Luo Guanglian , Wang Bin , Li Bin , Li Ruiwei , Luo Dongqi
Published: August 2022

Rural settlements in mountainous areas change slowly and are not easy to measure. Reclamation is an important spatial indication of their demise. To measure the spatial–temporal variation of rural settlements extinction from the perspective of regional reclamation projects, and to provide a reference for the scientific evolution of rural settlements in mountainous areas. Based on the data of reclamation projects in Chongqing, China, from 2017 to 2021, with the number of projects, the scale of construction and the scale of newly cultivated land as indicators, coefficient of variation, gravity center model and spatial autocorrelation were used to analyze the distribution characteristics, gravity shift and spatial pattern evolution characteristics of reclamation projects at different spatial scales. The results show that: (1) From the time dimension, the number of reclamation projects, the scale of construction and the scale of newly cultivated land all showed a downward trend, but the differences in the absolute and relative scales of each index gradually decreased, showing a spatiotemporal equilibrium trend. (2) Reclamation projects showed different agglomeration characteristics at different spatial scales. At the regional level, the reclamation projects are concentrated in the city cluster of the Three Gorges reservoir area in Northeast Chongqing. At the district/county level, the reclamation projects are mainly concentrated in Fengjie County (458), followed by Yunyang County (330) and Pengshui County (305), and the least is Wansheng District (32) with an average of about 165. (3) All the centers of gravity in the moving track of the reclamation project center of gravity are located in the city cluster of the Three Gorges reservoir area in northeast Chongqing, and the spatial distribution is geographically balanced. (4) There is a significant agglomeration in the distribution of reclamation projects at the district and county scales. The high-high agglomeration area was mainly concentrated in the city cluster of the Three Gorges reservoir area in northeast Chongqing, and the low-low agglomeration area was mainly distributed in the city proper of Chongqing. The extinction of rural settlements reclamation is affected by regional nature, economy and society, but the land policy is the main driving force. At the same time, we should carefully treat the counties where the rural settlements are disappearing too fast, so as to avoid the drastic changes in the amount and space of cultivated land associated with them.
How Are Land-Use/Land-Cover Indices and Daytime and Nighttime Land Surface Temperatures Related in Eleven Urban Centres in Different Global Climatic Zones?
Authors: Li Yuanzheng , Zhao Zezhi , Xin Yashu , Xu Ao , Xie Shuyan , Yan Yi , Wang Lan
Published: August 2022

Improving the urban thermal environment can enhance humans’ well-being. Nevertheless, it was not clear which land-use/land-cover (LU/LC) indices were optimal for explaining land surface temperatures (LSTs) and how they affected LSTs in cities in different climatic zones, especially during the nighttime. Thus, the Aqua/MODIS and Landsat/OLI data were mainly used to explore the optimal indices of building, vegetation, water and bare soil and to analyze their effects on LSTs in eleven urban centers in global distinct climatic regions. Results showed several LU/LC indices had high probabilities of being optimal indices to explain LSTs under different conditions. The daytime LSTs were usually significantly negatively correlated with vegetation indices and positively correlated with building and bare soil indices (p < 0.05). These relationships were stronger in the summer than winter. The nighttime LSTs were usually significantly positively and negatively correlated with building and vegetation indices in the summer, respectively (p < 0.05). These correlations were generally weaker during the nighttime than daytime. The nighttime LSTs were significantly positively and negatively correlated with water and bare soil indices, respectively (p < 0.05). Significant linear multiple regressions commonly existed between daytime and nighttime LSTs and four kinds of LU/LC indices (p < 0.05). These findings helped optimize urban thermal comfort, downscale city LSTs, etc.
The Case for Early Use of Glucagon-like Peptide-1 Receptor Agonists in Obstructive Sleep Apnea Patients with Comorbid Diabetes and Metabolic Syndrome
Authors: Sultana Rizwana , Sissoho Fatoumatta , Kaushik Vinod P. , Raji Mukaila A.
Published: August 2022

Patients with obstructive sleep apnea (OSA) have high rates of co-occurring type 2 diabetes, hypertension, obesity, stroke, congestive heart failure, and accelerated atherosclerotic cardiovascular diseases. These conditions frequently require multiple medications, raising the risk of polypharmacy, adverse drug–drug and drug–disease interactions, decreased quality of life, and increased healthcare cost in these patients. The current review of extant literature presents evidence supporting glucagon-like peptide-1 receptor agonists (GLP-1RA) as one pharmacologic intervention that provides a “one-stop shop” for OSA patients because of the multiple effects GLP-1RA has on comorbidities (e.g., hypertension, diabetes, obesity, metabolic syndrome, and atherosclerotic cardiovascular diseases) that commonly co-occur with OSA. Examples of glucagon-like peptide-1 receptor agonists approved by the FDA for diabetes (some of which are also approved for obesity) are liraglutide, exenatide, lixisenatide, dulaglutide, semaglutide, and albiglutide. Prescribing of GLP-1RAs to address these multiple co-occurring conditions has enormous potential to reduce polypharmacy, cost, and adverse drug events, and to improve quality of life for patients living with OSA and diabetes. We thus strongly advocate for increased and early use of GLP-1RA in OSA patients with co-occurring diabetes and other cardiometabolic conditions common in OSA.
Macrophages in Glioblastoma Development and Therapy: A Double-Edged Sword
Authors: Wu Mengwan , Shi Ying , Zhu Luyi , Chen Luoyi , Zhao Xinchen , Xu Chuan
Published: August 2022

Glioblastoma (GBM) is one of the leading lethal tumors, featuring aggressive malignancy and poor outcome to current standard temozolomide (TMZ) or radio-based therapy. Developing immunotherapies, especially immune checkpoint inhibitors, have improved patient outcomes in other solid tumors but remain fatigued in GBM patients. Emerging evidence has shown that GBM-associated macrophages (GAMs), comprising brain-resident microglia and bone marrow-derived macrophages, act critically in boosting tumor progression, altering drug resistance, and establishing an immunosuppressive environment. Based on its crucial role, evaluations of the safety and efficacy of GAM-targeted therapy are ongoing, with promising (pre)clinical evidence updated. In this review, we summarized updated literature related to GAM nature, the interplay between GAMs and GBM cells, and GAM-targeted therapeutic strategies.
Assessing the Effects of Landscape Change on the Occupancy Dynamics of the Greater White-Toothed Shrew Crocidura russula
Authors: Torre Ignasi , Díaz Mario
Published: August 2022

Land-use change is the main driver of biodiversity loss in the Mediterranean basin. New socio-economic conditions produced a rewilding process so that cultural landscapes are being invaded by more natural habitats. We analyze the effects of landscape change on the demography and the spatial distribution of Crocidura russula in six protected areas of the western Mediterranean basin. The study was conducted in the period 2008–2020 on 19 live trapping plots representing the three main natural habitats of the area (scrubland, pinewood, and holm oak woodland). We used a multiscale approach to ensure that the scale of response matched landscape structure (from plot to landscape) using either vegetation profiles (LiDAR) and land use data obtained from years 2007 and 2017. Statistical models (multiple-season single-species occupancy models) showed that C. russula populations were strongly associated to habitat features at the plot level. These models were used to predict occupancy at sampling units for the whole study area (850 km2), showing contrasting trends that shifted at relatively small spatial scales (expansions and retractions of species ranges). Parks showing extreme scrubland encroachment (−8% of area) and afforestation (+6%) significantly reduced habitat suitability for shrews and reductions in occupancy (−5%). Results would indicate faster changes in the spatial distribution of the target species than previously expected on the basis of climate change, driven by fast landscape changes.
Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity
Authors: He Shiyi , Yan Lu , Zhu Rongxin , Wei Hao , Wang Jianxiong , Zheng Lan , Zhang Ying
Published: August 2022

Disruption of circadian rhythms is related to disorders of glucose metabolism, and the molecular clock also exists in skeletal muscle. The ChIP-derived repressor of network oscillator (Chrono) and brain and muscle ARNT-like 1 (Bmal1) are core circadian components. Chrono is considered to be the repressor of Bmal1, and the Chrono–Bmal1 pathway is important in regulating the circadian rhythm; it has been speculated that this pathway could be a new mechanism for regulating glucose metabolism. The purpose of this study was to investigate the effects of Chrono on glucose metabolism in skeletal muscle and exercise capacity by using mice with skeletal-muscle-specific overexpression of Chrono (Chrono TG) and wild-type (WT) mice as the animal models. The results of this cross-sectional study indicated that the Chrono TG mice had an impaired glucose tolerance, lower exercise capacity, and higher levels of nonfasted blood glucose and glycogen content in skeletal muscle compared to WT mice. In addition, the Chrono TG mice also showed a significant increase in the amount of Chrono bound to Bmal1 according to a co-IP analysis; a remarkable decrease in mRNA expression of Tbc1d1, Glut4, Hk2, Pfkm, Pdp1, Gbe1, and Phka1, as well as in activity of Hk and protein expression of Ldhb; but higher mRNA expression of Pdk4 and protein expression of Ldha compared with those of WT mice. These data suggested the skeletal-muscle-specific overexpression of Chrono led to a greater amount of Chrono bound to Bmal1, which then could affect the glucose transporter, glucose oxidation, and glycogen utilization in skeletal muscle, as well as exercise capacity.
Review on Carbonation Study of Reinforcement Concrete Incorporating with Bacteria as Self-Healing Approach
Authors: Alshaeer Honin Ali Yahya , Irwan J. M. , Alshalif Abdullah Faisal , Al-Fakih Amin , Ewais Dina Yehia Zakaria , Salmi Abdelatif , Alhokabi Abdulmajeed Ali
Published: August 2022

This study carried out a comprehensive review to determine the carbonation process that causes the most deterioration and destruction of concrete. The carbonation mechanism involved using carbon dioxide (CO2) to penetrate the concrete pore system into the atmosphere and reduce the alkalinity by decreasing the pH level around the reinforcement and initiation of the corrosion process. The use of bacteria in the concrete was to increase the pH of the concrete by producing urease enzyme. This technique may help to maintain concrete alkalinity in high levels, even when the carbonation process occurs, because the CO2 accelerates to the concrete and then converts directly to calcium carbonate, CaCO3. Consequently, the self-healing of the cracks and the pores occurred as a result of the carbonation process and bacteria enzyme reaction. As a result of these reactions, the concrete steel is protected, and the concrete properties and durability may improve. However, there are several factors that control carbonation which have been grouped into internal and external factors. Many studies on carbonation have been carried out to explore the effect of bacteria to improve durability and concrete strength. However, an in-depth literature review revealed that the use of bacteria as a self-healing mechanism can still be improved upon. This review aimed to highlight and discuss the possibility of applying bacteria in concrete to improve reinforcement concrete.