bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Cancer Pain: Opioids within Tumor Microenvironment Affect Neuroinflammation, Tumor and Pain Evolution
Authors: Santoni Angela , Santoni Matteo , Arcuri Edoardo
Published: May 2022

Pain can be a devastating experience for cancer patients, resulting in decreased quality of life. In the last two decades, immunological and pain research have demonstrated that pain persistence is primarily caused by neuroinflammation leading to central sensitization with brain neuroplastic alterations and changes in pain responsiveness (hyperalgesia, and pain behavior). Cancer pain is markedly affected by the tumor microenvironment (TME), a complex ecosystem consisting of different cell types (cancer cells, endothelial and stromal cells, leukocytes, fibroblasts and neurons) that release soluble mediators triggering neuroinflammation. The TME cellular components express opioid receptors (i.e., MOR) that upon engagement by endogenous or exogenous opioids such as morphine, initiate signaling events leading to neuroinflammation. MOR engagement does not only affect pain features and quality, but also influences directly and/or indirectly tumor growth and metastasis. The opioid effects on chronic cancer pain are also clinically characterized by altered opioid responsiveness (tolerance and hyperalgesia), a hallmark of the problematic long-term treatment of non-cancer pain. The significant progress made in understanding the immune-mediated development of chronic pain suggests its exploitation for novel alternative immunotherapeutic approaches.
Cell Free Methylated Tumor DNA in Bronchial Lavage as an Additional Tool for Diagnosing Lung Cancer—A Systematic Review
Authors: Wen Sara Witting Christensen , Wen Jan , Hansen Torben Frøstrup , Jakobsen Anders , Hilberg Ole
Published: May 2022

This systematic review investigated circulating methylated tumor DNA in bronchial lavage fluid for diagnosing lung cancer. PROSPERO registration CRD42022309470. PubMed, Embase, Medline, and Web of Science were searched on 9 March 2022. Studies of adults with lung cancer or undergoing diagnostic workup for suspected lung cancer were included if they used bronchial lavage fluid, analyzed methylated circulating tumor DNA, and reported the diagnostic properties. Sensitivity, specificity, and lung cancer prevalence were summarized in forest plots. Risk of bias was assessed using the QUADAS-2 tool. A total of 25 studies were included. All were case-control studies, most studies used cell pellet for analysis by quantitative PCR. Diagnostic sensitivity ranged from 0% for a single gene to 97% for a four-gene panel. Specificity ranged from 8% for a single gene to 100%. The studies employing a gene panel decreased the specificity, and no gene panel had a perfect specificity of 100%. In conclusion, methylated circulating tumor DNA can be detected in bronchial lavage, and by employing a gene panel the sensitivity can be increased to clinically relevant levels. The available evidence regarding applicability in routine clinical practice is limited. Prospective, randomized clinical trials are needed to determine the further usefulness of this biomarker.
Neurokinin-1 Receptor (NK-1R) Antagonists as a New Strategy to Overcome Cancer Resistance
Authors: García-Aranda Marilina , Téllez Teresa , McKenna Lauraine , Redondo Maximino
Published: May 2022

Nowadays, the identification of new therapeutic targets that allow for the development of treatments, which as monotherapy, or in combination with other existing treatments can contribute to improve response rates, prognosis and survival of oncologic patients, is a priority to optimize healthcare within sustainable health systems. Recent studies have demonstrated the role of Substance P (SP) and its preferred receptor, Neurokinin 1 Receptor (NK-1R), in human cancer and the potential antitumor activity of NK-1R antagonists as an anticancer treatment. In this review, we outline the relevant studies published to date regarding the SP/NK-1R complex as a key player in human cancer and also evaluate if the repurposing of already marketed NK-1R antagonists may be useful in the development of new treatment strategies to overcome cancer resistance.
Clinical Significance of Molecular Alterations and Systemic Therapy for Meningiomas: Where Do We Stand?
Authors: Pellerino Alessia , Bruno Francesco , Palmiero Rosa , Pronello Edoardo , Bertero Luca , Soffietti Riccardo , Rudà Roberta
Published: May 2022

Meningiomas are common intracranial tumors that can be treated successfully in most cases with surgical resection and/or adjuvant radiotherapy. However, approximately 20% of patients show an aggressive clinical course with tumor recurrence or progressive disease, resulting in significant morbidity and increased mortality. Despite several studies that have investigated different cytotoxic agents in aggressive meningiomas in the past several years, limited evidence of efficacy and clinical benefit has been reported thus far. Novel molecular alterations have been linked to a particular clinicopathological phenotype and have been correlated with grading, location, and prognosis of meningiomas. In this regard, SMO, AKT, and PIK3CA mutations are typical of anterior skull base meningiomas, whereas KLF4 mutations are specific for secretory histology, and BAP1 alterations are common in progressive rhabdoid meningiomas. Alterations in TERT, DMD, and BAP1 correlate with poor outcomes. Moreover, some actionable mutations, including SMO, AKT1, and PIK3CA, regulate meningioma growth and are under investigation in clinical trials. PD-L1 and/or M2 macrophage expression in the microenvironment provides evidence for the investigation of immunotherapy in progressive meningiomas.
Semaphorin-3F/Neuropilin-2 Transcriptional Expression as a Predictive Biomarker of Occult Lymph Node Metastases in HNSCC
Authors: Meler-Claramonte Carla , Avilés-Jurado Francesc Xavier , Vilaseca Isabel , Terra Ximena , Bragado Paloma , Fuster Gemma , León Vintró Xavier , Camacho Mercedes
Published: May 2022

The expression of the semaphorin-3F (SEMA3F) and neuropilin-2 (NRP2) is involved in the regulation of lymphangiogenesis. The present study analyzes the relationship between the transcriptional expression of the SEMA3F-NRP2 genes and the presence of occult lymph node metastases in patients with cN0 head and neck squamous cell carcinomas. We analyzed the transcriptional expression of SEMA3F and NRP2 in a cohort of 53 patients with cN0 squamous cell carcinoma treated with an elective neck dissection. Occult lymph node metastases were found in 37.7% of the patients. Patients with occult lymph node metastases (cN0/pN+) had significantly lower SEMA3F expression values than patients without lymph node involvement (cN0/pN0). Considering the expression of the SEMA3F-NRP2 genes, patients were classified into two groups according to the risk of occult nodal metastasis: Group 1 (n = 34), high SEMA3F/low NRP2 expression, with a low risk of occult nodal involvement (14.7% cN0/pN+); Group 2 (n = 19), low SEMA3F or high SEMA3F/high NRP2 expression, with a high risk of occult nodal involvement (78.9% cN0/pN+). Multivariate analysis showed that patients in Group 2 had a 26.2 higher risk of lymph node involvement than patients in Group 1. There was a significant relationship between the transcriptional expression values of the SEMA3F-NRP2 genes and the risk of occult nodal metastases.
TRPM8-Rap1A Interaction Sites as Critical Determinants for Adhesion and Migration of Prostate and Other Epithelial Cancer Cells
Authors: Chinigò Giorgia , Grolez Guillaume P. , Audero Madelaine , Bokhobza Alexandre , Bernardini Michela , Cicero Julien , Toillon Robert-Alain , Bailleul Quentin , Visentin Luca , Ruffinatti Federico Alessandro , Brysbaert Guillaume , Lensink Marc F. , De Ruyck Jerome , Cantelmo Anna Rita , Fiorio Pla Alessandra , Gkika Dimitra
Published: May 2022

Emerging evidence indicates that the TRPM8 channel plays an important role in prostate cancer (PCa) progression, by impairing the motility of these cancer cells. Here, we reveal a novel facet of PCa motility control via direct protein-protein interaction (PPI) of the channel with the small GTPase Rap1A. The functional interaction of the two proteins was assessed by active Rap1 pull-down assays and live-cell imaging experiments. Molecular modeling analysis allowed the identification of four putative residues involved in TRPM8-Rap1A interaction. Point mutations of these sites impaired PPI as shown by GST-pull-down, co-immunoprecipitation, and PLA experiments and revealed their key functional role in the adhesion and migration of PC3 prostate cancer cells. More precisely, TRPM8 inhibits cell migration and adhesion by trapping Rap1A in its GDP-bound inactive form, thus preventing its activation at the plasma membrane. In particular, residues E207 and Y240 in the sequence of TRPM8 and Y32 in that of Rap1A are critical for the interaction between the two proteins not only in PC3 cells but also in cervical (HeLa) and breast (MCF-7) cancer cells. This study deepens our knowledge of the mechanism through which TRPM8 would exert a protective role in cancer progression and provides new insights into the possible use of TRPM8 as a new therapeutic target in cancer treatment.
Vulvar Cancer: 2021 Revised FIGO Staging System and the Role of Imaging
Authors: Virarkar Mayur , Vulasala Sai Swarupa , Daoud Taher , Javadi Sanaz , Lall Chandana , Bhosale Priya
Published: May 2022

Vulvar cancer is a rare gynecological malignancy. It constitutes 5–8% of all gynecologic neoplasms, and squamous cell carcinoma is the most common variant. This article aims to review the etiopathogenesis revised 2021 International Federation of Gynecology and Obstetrics (FIGO) classification and emphasize imaging in the staging of vulvar cancer. The staging has been regulated by FIGO since 1969 and is subjected to multiple revisions. Previous 2009 FIGO classification is limited by the prognostic capability, which prompted the 2021 revisions and issue of a new FIGO classification. Although vulvar cancer can be visualized clinically, imaging plays a crucial role in the staging of the tumor, assessing the tumor extent, and planning the management. In addition, sentinel lymph node biopsy facilitates the histopathological staging of the draining lymph node, thus enabling early detection of tumor metastases and better survival rates.
Engineering Induced Pluripotent Stem Cells for Cancer Immunotherapy
Authors: Zhou Yang , Li Miao , Zhou Kuangyi , Brown James , Tsao Tasha , Cen Xinjian , Husman Tiffany , Bajpai Aarushi , Dunn Zachary Spencer , Yang Lili
Published: May 2022

Cell-based immunotherapy, such as chimeric antigen receptor (CAR) T cell therapy, has revolutionized the treatment of hematological malignancies, especially in patients who are refractory to other therapies. However, there are critical obstacles that hinder the widespread clinical applications of current autologous therapies, such as high cost, challenging large-scale manufacturing, and inaccessibility to the therapy for lymphopenia patients. Therefore, it is in great demand to generate the universal off-the-shelf cell products with significant scalability. Human induced pluripotent stem cells (iPSCs) provide an “unlimited supply” for cell therapy because of their unique self-renewal properties and the capacity to be genetically engineered. iPSCs can be differentiated into different immune cells, such as T cells, natural killer (NK) cells, invariant natural killer T (iNKT) cells, gamma delta T (γδ T), mucosal-associated invariant T (MAIT) cells, and macrophages (Mφs). In this review, we describe iPSC-based allogeneic cell therapy, the different culture methods of generating iPSC-derived immune cells (e.g., iPSC-T, iPSC-NK, iPSC-iNKT, iPSC-γδT, iPSC-MAIT and iPSC-Mφ), as well as the recent advances in iPSC-T and iPSC-NK cell therapies, particularly in combinations with CAR-engineering. We also discuss the current challenges and the future perspectives in this field towards the foreseeable applications of iPSC-based immune therapy.
Regulatory Role of the Adipose Microenvironment on Ovarian Cancer Progression
Authors: Chehade Hussein , Tedja Roslyn , Ramos Harry , Bawa Tejeshwar Singh , Adzibolosu Nicholas , Gogoi Radhika , Mor Gil , Alvero Ayesha B.
Published: May 2022

The tumor microenvironment of ovarian cancer is the peritoneal cavity wherein adipose tissue is a major component. The role of the adipose tissue in support of ovarian cancer progression has been elucidated in several studies from the past decades. The adipocytes, in particular, are a major source of factors, which regulate all facets of ovarian cancer progression such as acquisition of chemoresistance, enhanced metastatic potential, and metabolic reprogramming. In this review, we summarize the relevant studies, which highlight the role of adipocytes in ovarian cancer progression and offer insights into unanswered questions and possible future directions of research.
Combined Biological and Photocatalytic Degradation of Dibutyl Phthalate in a Simulated Wastewater Treatment Plant
Authors: Mphahlele Ipoteng Justice , Malinga Soraya Phumzile , Dlamini Langelihle Nsikayezwe
Published: May 2022

The removal of organic pollutant in wastewater has become a major priority in water treatment. In this study, organic pollutant dibutyl phthalate (DBP) has been biologically and photocatalytically degraded in wastewater using modified transition metal dichalcogenides. The as-synthesized nanoparticles were characterized using various characterization techniques, which includes XRD, Raman, FT-IR, SEM, TEM, UV-Vis, XPS, PL, EIS, and photocurrent responses. The nanoparticles synthesized by slightly modified hydrothermal method depicted a hexagonal phase, as evidenced by XRD and Raman analyses. The biological degradation of 69% dibutyl phthalate was achieved. Moreover, the total organic carbon removal efficiency of 70% was further achieved. Incorporating biological and photocatalytic systems significantly improved dibutyl phthalate removal in secondary effluent by three folds when compared to the unilateral operating setup. The optimized parameters such as pH = 7, 5 ppm and DBP concentration with the addition of 10 mg catalysts loading were employed for the photocatalytic degradation of dibutyl phthalate in water. Pristine WS2 exhibited photocatalytic efficiencies of 46% after 60 min illumination. The use of dual system 3% Ce/Gd-WS2 exhibited the highest photodegradation of 85%, with a chemical oxygen demand of 80% and total organic carbon of 77%. The enhanced activity by the composite is attested to the formation of heterojunction exhibiting excellent charge separation and low rate of recombination. The 3% Ce/Gd-WS2 can be used up to seven times and still achieve a degradation of 56%.
Tetrabutyl Ammonium Salts of Keggin-Type Vanadium-Substituted Phosphomolybdates and Phosphotungstates for Selective Aerobic Catalytic Oxidation of Benzyl Alcohol
Authors: Díaz Juan , Pizzio Luis R. , Pecchi Gina , Campos Cristian H. , Azócar Laura , Briones Rodrigo , Romero Romina , Henríquez Adolfo , Gaigneaux Eric M. , Contreras David
Published: May 2022

A series of tetrabutyl ammonium (TBA) salts of V-included Keggin-type polyoxoanions with W (TBA4PW11V1O40 and TBA5PW10V2O40) and Mo (TBA4PMo11V1O40 and TBA5PMo10V2O40) as addenda atoms were prepared using a hydrothermal method. These synthesized materials were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), UV-Vis diffuse reflectance (DRS UV-Vis), thermogravimetric analysis (TGA), CHN elemental analysis (EA), inductively coupled plasma spectrometry (ICP-MS), and N2 physisorption techniques to assess their physicochemical/textural properties and correlate them with their catalytic performances. According to FT-IR and DRS UV-Vis, (PVXW(Mo)12−XO40)(3+X)− anions are the main species present in the TBA salts. Additionally, CHN-EA and ICP-MS revealed that the desired stoichiometry was obtained. Their catalytic activities in the liquid-phase aerobic oxidation of benzyl alcohol to benzaldehyde were studied at 5 bar of O2 at 170 °C. Independently of the addenda atom nature, the catalytic activity increased with the number of V in the Keggin anion structure. For both series of catalysts, TBA salts of polyoxometalates with the highest V-substitution degree (TBA5PMo10V2O40 and TBA5PW10V2O40) showed higher activity. The maximum benzyl alcohol conversions obtained were 93% and 97% using (TBA)5PMo10V2O40 and (TBA)5PW10V2O40 as catalysts, respectively. In all the cases, the selectivity toward benzaldehyde was higher than 99%.
Preparation of TiO2-CNT-Ag Ternary Composite Film with Enhanced Photocatalytic Activity via Plasma-Enhanced Chemical Vapor Deposition
Authors: Lang Jianghua , Takahashi Kazuma , Kubo Masaru , Shimada Manabu
Published: May 2022

In this study, a TiO2-CNT-Ag ternary composite film was successfully synthesized using the plasma-enhanced chemical vapor deposition method by simultaneously feeding a carbon nanotube (CNT)/Ag suspension and titanium tetraisopropoxide gas. The prepared TiO2-CNT-Ag film was characterized by scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and ultraviolet-visible spectroscopy. Moreover, the Ag/Ti ratio of the film was confirmed using an inductivity-coupled plasma optical emission spectrometer. The performance of the TiO2-composite film for the degradation of rhodamine 6G under simulated solar light irradiation was evaluated. The rate constant of the prepared TiO2-CNT-Ag for rhodamine 6G degradation was approximately 1.8 times greater than that of prepared TiO2. This result indicates that the addition of CNT and Ag significantly improved the photocatalytic activity of the prepared films.
Unraveling the Molecular Basis of the Dystrophic Process in Limb-Girdle Muscular Dystrophy LGMD-R12 by Differential Gene Expression Profiles in Diseased and Healthy Muscles
Authors: Depuydt Christophe E. , Goosens Veerle , Janky Rekin’s , D’Hondt Ann , De Bleecker Jan L. , Noppe Nathalie , Derveaux Stefaan , Thal Dietmar R. , Claeys Kristl G.
Published: May 2022

Limb-girdle muscular dystrophy R12 (LGMD-R12) is caused by two mutations in anoctamin-5 (ANO5). Our aim was to identify genes and pathways that underlie LGMD-R12 and explain differences in the molecular predisposition and susceptibility between three thigh muscles that are severely (semimembranosus), moderately (vastus lateralis) or mildly (rectus femoris) affected in this disease. We performed transcriptomics on these three muscles in 16 male LGMD-R12 patients and 15 age-matched male controls. Our results showed that LGMD-R12 dystrophic muscle is associated with the expression of genes indicative of fibroblast and adipocyte replacement, such as fibroadipogenic progenitors and immune cell infiltration, while muscle protein synthesis and metabolism were downregulated. Muscle degeneration was associated with an increase in genes involved in muscle injury and inflammation, and muscle repair/regeneration. Baseline differences between muscles in healthy individuals indicated that muscles that are the most affected by LGMD-R12 have the lowest expression of transcription factor networks involved in muscle (re)generation and satellite stem cell activation. Instead, they show relative high levels of fetal/embryonic myosins, all together indicating that muscles differ in their baseline regenerative potential. To conclude, we profiled the gene expression landscape in LGMD-R12, identified baseline differences in expression levels between differently affected muscles and characterized disease-associated changes.
Antigen Cross-Presentation by Murine Proximal Tubular Epithelial Cells Induces Cytotoxic and Inflammatory CD8+ T Cells
Authors: Linke Alexandra , Cicek Hakan , Müller Anne , Meyer-Schwesinger Catherine , Melderis Simon , Wiech Thorsten , Wegscheid Claudia , Ridder Julius , Steinmetz Oliver M. , Diehl Linda , Tiegs Gisa , Neumann Katrin
Published: May 2022

Immune-mediated glomerular diseases are characterized by infiltration of T cells, which accumulate in the periglomerular space and tubulointerstitium in close contact to proximal and distal tubuli. Recent studies described proximal tubular epithelial cells (PTECs) as renal non-professional antigen-presenting cells that stimulate CD4+ T-cell activation. Whether PTECs have the potential to induce activation of CD8+ T cells is less clear. In this study, we aimed to investigate the capacity of PTECs for antigen cross-presentation thereby modulating CD8+ T-cell responses. We showed that PTECs expressed proteins associated with cross-presentation, internalized soluble antigen via mannose receptor-mediated endocytosis, and generated antigenic peptides by proteasomal degradation. PTECs induced an antigen-dependent CD8+ T-cell activation in the presence of soluble antigen in vitro. PTEC-activated CD8+ T cells expressed granzyme B, and exerted a cytotoxic function by killing target cells. In murine lupus nephritis, CD8+ T cells localized in close contact to proximal tubuli. We determined enhanced apoptosis in tubular cells and particularly PTECs up-regulated expression of cleaved caspase-3. Interestingly, induction of apoptosis in the inflamed kidney was reduced in the absence of CD8+ T cells. Thus, PTECs have the capacity for antigen cross-presentation thereby inducing cytotoxic CD8+ T cells in vitro, which may contribute to the pathology of immune-mediated glomerulonephritis.
Fourier Ptychographic Microscopy via Alternating Direction Method of Multipliers
Authors: Wang Aiye , Zhang Zhuoqun , Wang Siqi , Pan An , Ma Caiwen , Yao Baoli
Published: May 2022

Fourier ptychographic microscopy (FPM) has risen as a promising computational imaging technique that breaks the trade-off between high resolution and large field of view (FOV). Its reconstruction is normally formulated as a blind phase retrieval problem, where both the object and probe have to be recovered from phaseless measured data. However, the stability and reconstruction quality may dramatically deteriorate in the presence of noise interference. Herein, we utilized the concept of alternating direction method of multipliers (ADMM) to solve this problem (termed ADMM-FPM) by breaking it into multiple subproblems, each of which may be easier to deal with. We compared its performance against existing algorithms in both simulated and practical FPM platform. It is found that ADMM-FPM method belongs to a global optimization algorithm with a high degree of parallelism and thus results in a more stable and robust phase recovery under noisy conditions. We anticipate that ADMM will rekindle interest in FPM as more modifications and innovations are implemented in the future.
The Role of N6-Methyladenosine in the Promotion of Hepatoblastoma: A Critical Review
Authors: Auld Finn Morgan , Sergi Consolato M. , Leng Roger , Shen Fan
Published: May 2022

Hepatoblastoma (HB) is a rare primary malignancy of the developing fetal liver. Its course is profoundly influenced by genetics, in the context of sporadic mutation or genetic syndromes. Conventionally, subtypes of HB are histologically determined based on the tissue type that is recapitulated by the tumor and the direction of its differentiation. This classification is being reevaluated based on advances on molecular pathology. The therapeutic approach comprises surgical intervention, chemotherapy (in a neoadjuvant or post-operative capacity), and in some cases, liver transplantation. Although diagnostic modalities and treatment options are evolving, some patients experience complications, including relapse, metastatic spread, and suboptimal response to chemotherapy. As yet, there is no consistent framework with which such outcomes can be predicted. N6-methyladenosine (m6A) is an RNA modification with rampant involvement in the normal processing of cell metabolism and neoplasia. It has been observed to impact the development of a variety of cancers via its governance of gene expression. M6A-associated genes appear prominently in HB. Literature data seem to underscore the role of m6A in promotion and clinical course of HB. Illuminating the pathogenetic mechanisms that drive HB are promising additions to the understanding of the clinically aggressive tumor behavior, given its potential to predict disease course and response to therapy. Implicated genes may also act as targets to facilitate the evolving personalized cancer therapy. Here, we explore the role of m6A and its genetic associates in the promotion of HB, and the impact this may have on the management of this neoplastic disease.
Focused Ultrasound Treatment of a Spheroid In Vitro Tumour Model
Authors: Landgraf Lisa , Kozlowski Adam , Zhang Xinrui , Fournelle Marc , Becker Franz-Josef , Tretbar Steffen , Melzer Andreas
Published: May 2022

Focused ultrasound (FUS) is a non-invasive technique producing a variety of biological effects by either thermal or mechanical mechanisms of ultrasound interaction with the targeted tissue. FUS could bring benefits, e.g., tumour sensitisation, immune stimulation, and targeted drug delivery, but investigation of FUS effects at the cellular level is still missing. New techniques are commonly tested in vitro on two-dimensional (2D) monolayer cancer cell culture models. The 3D tumour model—spheroid—is mainly utilised to mimic solid tumours from an architectural standpoint. It is a promising method to simulate the characteristics of tumours in vitro and their various responses to therapeutic alternatives. This study aimed to evaluate the effects of FUS on human prostate and glioblastoma cancer tumour spheroids in vitro. The experimental follow-up enclosed the measurements of spheroid integrity and growth kinetics, DNA damage, and cellular metabolic activity by measuring intracellular ATP content in the spheroids. Our results showed that pulsed FUS treatment induced molecular effects in 3D tumour models. With the disruption of the spheroid integrity, we observed an increase in DNA double-strand breaks, leading to damage in the cancer cells depending on the cancer cell type.
Exploring the Adsorption of Pb on Microalgae-Derived Biochar: A Versatile Material for Environmental Remediation and Electroanalytical Applications
Authors: Binda Gilberto , Faccini Davide , Zava Martina , Pozzi Andrea , Dossi Carlo , Monticelli Damiano , Spanu Davide
Published: May 2022

Biochar, a carbon material obtained by pyrolysis of biomasses, is increasingly applied in environmental remediation and sensing thanks to its functional properties, cost-effectiveness and eco-friendliness. The adsorption capacity of biochar, strictly dependent on its specific surface area, heteroatom doping and surface functional groups, is crucial for these applications. Here, biochar produced at low temperature (350 °C) from a marine microalga (Nannochloropsis sp.) is proposed as an efficient adsorbent of lead (II) ions in aqueous solution; this production strategy promotes the natural self-doping of biochar without requiring harsh conditions. The kinetics and thermodynamics of the adsorption process, as well as the effect of pH, ionic strength and dissolved organic matter on the adsorption efficiency were systematically assessed. The microalgae-derived biochar shows superior adsorption performances compared to a nutshell-derived one (used as a reference of lignocellulosic feedstocks) under all the tested conditions. The microalgae-derived biochar was finally used to decorate screen-printed carbon electrodes to improve the electroanalytical performances towards the voltammetric detection of lead (II) ions. A two-fold increase in sensitivity was obtained compared to the unmodified electrode thanks to the enhanced electron transfer and adsorption properties provided by biochar. These results highlight the potentialities of microalgae-derived biochar for environmental and sensing applications.
Factor Structure of the KABC-II at Ages 5 and 6: Is It Valid in a Clinical Sample?
Authors: Renner Gerolf , Irblich Dieter , Schroeder Anne
Published: May 2022

The factor structure of the German edition of the KABC-II for ages 5 and 6 was examined in a clinical sample. Participants were 450 children ages 5 and 6 who had been assessed due to various behavioral, emotional, or developmental disorders in five Centers for Social Pediatrics (SPCs). Confirmatory factor analyses of the standard test structure including core subtests of the Cattell-Horn-Carroll model and of the Luria model were conducted using maximum likelihood estimation. Several modified structures derived from CHC ability classifications were evaluated. Second-order factor structures corresponding to the standard test structure of the KABC-II demonstrated an adequate global fit for both theoretical models and were superior to unidimensional models. The fit of bifactor models was comparable to second-order models. In all subtests, the general factor accounted for more variance than group factors (broad abilities). However, in more than half of the subtests, unique variance explained the largest portion of the variance. The scale Learning/Glr showed a lack of convergent validity. At age 6, a model omitting subtest Rover significantly improved the fit. In the combined sample of 5- and 6-year-old children, both second-order and bifactor models with nine subtests demonstrated excellent fit.
Association between Cardiopulmonary Capacity and Body Mass Composition in Children and Adolescents with High Body Weight: A Cross-Sectional Study
Authors: Dobrowolska Agata , Domagalska-Szopa Małgorzata , Siwiec Andrzej , Szopa Andrzej
Published: May 2022

(1) Background: Excessive body weight is a global problem in the 21st century. Children and adolescents, in particular, are at risk. Recently, there has been an increasing interest in the relationship between aerobic capacity and body composition. Therefore, this study aimed to determine the association between the individual parameters of cardiopulmonary capacity obtained in cardiopulmonary exercise testing (CPET) and selected parameters of body mass composition in high-BMI children and children over the 85th percentile according to the WHO growth reference. (2) Materials and Method: The research included 100 children of school-age (7–15 years) with an excessive BMI, i.e., over the 85th percentile as per the WHO Growth Reference (BMI percentile 95.21 ± 4.65; Z-score BMI: 2.07 ± 0.94). The study consisted of three parts: anthropometric measurements, measurement of body mass composition using a body composition analyzer (TANITA MC-780 S MA) using the bioimpedance method, and a cardiopulmonary exercise test on a pediatric cycle ergometer (Corival Pediatric, Lode BV) using the Godfrey protocol; (3) Results: The correlation between BMI and fat mass (FM) was very high (rho = 0.83; p = 0.00) with moderate body fat percentage (BF%) (rho = 0.48; p = 0.00). There was a relevant correlation between the amount of fat-free mass in total body mass and cardiopulmonary capacity expressed as the absolute aerobic capacity (VO2peak) (rho = 0.55; p = 0.00). (4) Conclusions: In the case of children and youth with higher BMI, there was a correlation between the amount of fat-free mass in total body mass and cardiopulmonary capacity in terms of absolute aerobic capacity.
Effect of Porcine Placental Extract Mixture on Alcohol-Induced Hepatotoxicity in Rats
Authors: Kim Se-Mi , Diao Wen-Jing , An Wen , Kim Hyun-Jin , Lim Ha-Jong , Kim Keun-Nam , Bae Gun-Won , Kang Ju-Seop
Published: May 2022

This study was conducted to examine the effect of porcine placenta extract mixture (pPEM, enzymatic/acidic extract = 1/3) on alcoholic hepatotoxicity after pPEM dosing with alcohol in rats. The experimental groups were normal, control, silymarin, three pPEM (590, 1771, and 2511 mg/kg/day, po), and silymarin (100 mg/kg/day, po) groups (n = 10). Alcoholic hepatotoxicity was caused by a liquid ethanol diet for 4 weeks. The effect of pPEM and silymarin on alcoholic hepatotoxicity was evaluated by serology, hepatic ADH and ALDH activities, and histopathological findings. After oral dosing with alcohol for 4 weeks, ALT and AST were significantly increased to 33.7 → 115.6 and 81.37 → 235.0 in the alcohol group, respectively. These levels were decreased significantly to 83.9 and 126.7 in the silymarin group and dose-dependently to 73.6–56.9 and 139.2–122.8 in all pPEM groups. Hepatic ADH and ALDH might have been increased in the control and not in the silymarin and pPEM groups for hepatic ADH. All pPEM groups exhibited no effects on hepatic ALDH except for the high pPEM group. Mild inflammation and fatty lesions were observed in the alcohol group and were attenuated in the silymarin and pPEM groups. As a results, the pPEM showed protective activities against alcoholic hepatotoxicity on the serological markers, hepatic ADH and ALDH, and pathological findings.
In Silico Analysis of Peptide-Based Derivatives Containing Bifunctional Warheads Engaging Prime and Non-Prime Subsites to Covalent Binding SARS-CoV-2 Main Protease (Mpro)
Authors: Brogi Simone , Rossi Sara , Ibba Roberta , Butini Stefania , Calderone Vincenzo , Campiani Giuseppe , Gemma Sandra
Published: May 2022

Despite the progress of therapeutic approaches for treating COVID-19 infection, the interest in developing effective antiviral agents is still high, due to the possibility of the insurgence of viable SARS-CoV-2-resistant strains. Accordingly, in this article, we describe a computational protocol for identifying possible SARS-CoV-2 Mpro covalent inhibitors. Combining several in silico techniques, we evaluated the potential of the peptide-based scaffold with different warheads as a significant alternative to nitriles and aldehyde electrophilic groups. We rationally designed four potential inhibitors containing difluorstatone and a Michael acceptor as warheads. In silico analysis, based on molecular docking, covalent docking, molecular dynamics simulation, and FEP, indicated that the conceived compounds could act as covalent inhibitors of Mpro and that the investigated warheads can be used for designing covalent inhibitors against serine or cysteine proteases such as SARS-CoV-2 Mpro. Our work enriches the knowledge on SARS-CoV-2 Mpro, providing a novel potential strategy for its inhibition, paving the way for the development of effective antivirals.
Grossular Exsolution at Pyrope Dislocation: New Evidence for the Ultradeep Origin of Dabie Orogenic Peridotite
Authors: Xie Zhanjun , Liu Xiangwen , Jin Zhenmin , Liu Xiaoqing
Published: May 2022

Exsolution and dislocation microstructures are an important basis to decipher the conditions of metamorphic deformation and evolution processes of its host minerals and rocks. The grossular-rich exsolution in pyrope-rich garnet grains of Bixiling orogenic crustal cumulative peridotite, Dabie orogen, China, was studied by electron backscatter diffraction (EBSD), conventional and high-resolution transmission electron microscopy (TEM/HRTEM) and electron-microprobe analysis (EMPA). Our results indicate that the precursor pyrope-rich host grains had undergone plastic deformation and developed numerous dislocation microstructures before the grossular precipitated. When the pressure and/or temperature decreased during the exhumation of subducted slab, the grossular-rich lamellae exsolved and precipitated at the dislocation structures of host and inherited their shapes. EBSD and TEM analyses show that the crystallographic orientation of exsolution is controlled by, and coherent with, the host grain. These exsolution textures and the chemical composition of precursor garnet correspond to a balance pressure–temperature (P–T) condition of >6 GPa and >850 °C based on the previous thermodynamic models, which indicates that the origin depth of the Bixiling garnet peridotite should be more than 200 km.
Psychological Problems among Head and Neck Cancer Patients in Relation to Utilization of Healthcare and Informal Care and Costs in the First Two Years after Diagnosis
Authors: van Beek Florie E. , Jansen Femke , Baatenburg de Jong Rob J. , Langendijk Johannes A. , Leemans C. René , Smit Johannes H. , Takes Robert P. , Terhaard Chris H. J. , Custers José A. E. , Prins Judith B. , Lissenberg-Witte Birgit I. , Verdonck-de Leeuw Irma M.
Published: May 2022

Background: To investigate associations between psychological problems and the use of healthcare and informal care and total costs among head and neck cancer (HNC) patients. Method: Data were used of the NETherlands QUality of Life and Biomedical Cohort study. Anxiety and depression disorder (diagnostic interview), distress, symptoms of anxiety and depression (HADS), and fear of cancer recurrence (FCR) and cancer worry scale (CWS) were measured at baseline and at 12-month follow-up. Care use and costs (questionnaire) were measured at baseline, 3-, 6-, 12-, and 24-month follow-up. Associations between psychological problems and care use/costs were investigated using logistic and multiple regression analyses. Results: Data of 558 patients were used. Distress, symptoms of anxiety or depression, FCR, and/or anxiety disorder at baseline were significantly associated with higher use of primary care, supportive care, and/or informal care (odds ratios (ORs) between 1.55 and 4.76). Symptoms of anxiety, FCR, and/or depression disorder at 12-month follow-up were significantly associated with use of primary care, supportive care, and/or informal care (ORs between 1.74 and 6.42). Distress, symptoms of anxiety, and FCR at baseline were associated with higher total costs. Discussion: HNC patients with psychological problems make more use of healthcare and informal care and have higher costs. This is not the result of worse clinical outcomes.
Three-Dimensional Quantification of Copepods Predictive Distributions in the Ross Sea: First Data Based on a Machine Learning Model Approach and Open Access (FAIR) Data
Authors: Grillo Marco , Huettmann Falk , Guglielmo Letterio , Schiaparelli Stefano
Published: May 2022

Zooplankton is a fundamental group in aquatic ecosystems representing the base of the food chain. It forms a link between the lower trophic levels with secondary consumers and shows marked fluctuations in populations with environmental change, especially reacting to heating and water acidification. Marine copepods account for approx. 70% of the abundance of zooplankton and are a target of monitoring activities in key areas such as the Southern Ocean. In this study, we have used FAIR-inspired legacy data (dating back to the 1980s) collected in the Ross Sea by the Italian National Antarctic Program at GBIF.org. Together with other open-access GIS data sources and tools, it allows one to generate, for the first time, three-dimensional predictive distribution maps for twenty-six copepod species. These predictive maps were obtained by applying machine learning techniques to grey literature data, which were visualized in open-source GIS platforms. In a Species Distribution Modeling (SDM) framework, we used machine learning with three types of algorithms (TreeNet, RandomForest, and Ensemble) to analyze the presence and absence of copepods in different areas and depth classes as a function of environmental descriptors obtained from the Polar Macroscope Layers present in Quantartica. The models allow, for the first time, to map-predict the food chain per depth class in quantitative terms, showing the relative index of occurrence (RIO) in 3Dimensions and identifying the presence of each copepod species analyzed in the Ross Sea, a globally-relevant wilderness area of conservation concern. Our results show marked geographical preferences that vary with species and trophic strategy. This study demonstrates that machine learning is a successful method in accurately predicting the Antarctic copepod presence, also providing useful data to orient future sampling and the management of wildlife and conservation.
Interannual Winter Site Fidelity for Yellow and Black Rails
Authors: Butler Christopher J. , Olsen Tabitha W. , Kephart Bailey , Wilson Jennifer K. , Haverland Amanda A.
Published: May 2022

Yellow Rail (Coturnicops noveboracensis) is a species of conservation concern, while the Eastern Black Rail (Laterallus jamaicensis jamaicensis) has recently been listed as Threatened. Both species winter primarily in coastal areas from Texas through North Carolina. Between-year winter site fidelities of these species have not previously been reported, so we analyzed the recapture histories of Yellow Rails banded in southeastern Oklahoma (from 2008 to 2018) and coastal Texas (from 2006 to 2018), as well as Black Rails banded in Texas from 2006 to 2018. We banded 111 Yellow Rails in Oklahoma and 421 Yellow Rails in Texas during this time, as well as 94 Black Rails in Texas. Although Yellow Rails were routinely recaptured within season, only five individuals were recaptured between years. All recaptured birds were in Texas. Black Rails likewise exhibited low interannual site fidelity, with no interannual recaptures. The apparent low interannual site fidelity of Yellow Rails (1.1% in Texas, 0% in Oklahoma) and Black Rails (0%) is similar to that reported for other grassland species wintering in grasslands in this area (e.g., LeConte’s Sparrow (Ammodramus leconteii), Henslow’s Sparrow (A. henslowii), and Sedge Wren (Cistothorus stellaris)), and we speculate that low site fidelity could potentially be advantageous for species that use early successional habitats.
Poor Performance of Angiotensin II Enzyme-Linked Immuno-Sorbent Assays in Mostly Hypertensive Cohort Routinely Screened for Primary Aldosteronism
Authors: Łebek-Szatańska Agnieszka , Papierska Lucyna , Glinicki Piotr , Zgliczyński Wojciech
Published: May 2022

Primary aldosteronism (PA) is the most common, but broadly underdiagnosed, form of hormonal hypertension. To improve screening procedures, current biochemical approaches aim to determine newly appreciated angiotensin II (Ang II) and calculate the aldosterone-to-angiotensin II ratio (AA2R). Thus, the aim of this study was to assess the diagnostic performance of these screening tests in comparison to the aldosterone-to-direct renin ratio (ADRR), which is routinely used. Cheap and available ELISA was used for Ang II measurement. To our knowledge, this is the first study of this laboratory method’s usage in PA. The study cohort included 20 PA patients and 80 controls. Ang II concentrations were comparable between PA and non-PA patients (773.5 vs. 873.2 pg/mL, p = 0.23, respectively). The AA2R was statistically significantly higher in PA group when compared with non-PA (0.024 vs. 0.012 ng/dL/pg/mL, p < 0.001). However, the diagnostic performance of the AA2R was significantly worse than that of the ADRR (AUROC 0.754 vs. 0.939, p < 0.01). The sensitivity and specificity of the AA2R were 70% and 76.2%, respectively. Thus, the AA2R was not effective as a screening tool for PA. Our data provide important arguments in the discussion on the unsatisfactory accuracy of renin–angiotensin system evaluation by recently repeatedly used ELISA tests.
Physical Health, Media Use, Stress, and Mental Health in Pregnant Women during the COVID-19 Pandemic
Authors: Eleftheriades Makarios , Vousoura Eleni , Eleftheriades Anna , Pervanidou Panagiota , Zervas Iannis M. , Chrousos George , Vlahos Nikolaos F. , Sotiriadis Alexandros
Published: May 2022

Background: The COVID-19 pandemic has led to significant changes in the care of pregnant women and their fetuses. Emerging data show elevated depression and anxiety symptoms among pregnant women. Aims: The purpose of this article is to investigate the psychological and behavioral impact of the COVID-19 pandemic on pregnant women in Greece during the first national lockdown. Methods: We used a cross-sectional, anonymous survey to collect data in two fetal medicine clinics in the largest urban centers of Greece during the months of April and May 2020. The questionnaire was largely based on the CoRonavIruS Health Impact Survey (CRISIS), and assessed sociodemographic characteristics, general health and obstetric data and COVID-19-related worries and life changes. Mood symptoms, substance use and lifestyle behaviors were assessed at two time points (3 months prior to the pandemic and the 2 weeks before taking the survey), while perceived stress was measured with the perceived stress scale (PSS-14). Results: A total of 308 pregnant women (Mage = 34.72), with a mean gestation of 21.19 weeks participated in the study. Over one-third of the women found COVID-19 restrictions stressful, and their highest COVID-19-related worry was having to be isolated from their baby. Mean PSS-14 score was 21.94, suggesting moderate stress. The strongest predictors of stress were physical and mental health status before COVID-19 and having experienced a stressful life event during their pregnancy. Compared to 3 months before the pandemic, women reported higher scores on mood symptoms (p < 0.001), TV use (p = 0.01) and social media use (p = 0.031) in the last 2 weeks before taking the survey. Conclusion: Our study provides important preliminary evidence of the negative impact of the COVID-19 pandemic and the lockdown on pregnant women’s well-being and functioning.
Validation of GeneFinder COVID-19 Ag Plus Rapid Test and Its Potential Utility to Slowing Infection Waves: A Single-Center Laboratory Evaluation Study
Authors: Peronace Cinzia , Tallerico Rossana , Colosimo Manuela , Sacco Vanessa , Talarico Roberta , De Fazio Marco , Pasceri Federica , Talotta Ilenia , Panduri Giuseppina , Kim Jung-Hee , Cione Erika , Minchella Pasquale
Published: May 2022

Diagnostic laboratory tools are essential to keep everyone safe and track newly emerging variants; on the other hand, “filter” screening tests recognizing positivity are valuable tools to avoid hectic laboratory work that, besides COVID-19, are also part of the routine. Therefore, complementary assays, such as rapid antigen tests (RATs), are essential in controlling and monitoring virus spread within the community, especially in the asymptomatic population. A subset of nasopharyngeal swab specimens resulted in SARS-CoV-2 positive and investigated for genomic characterization were used for RAT validation. RATs were performed immediately after sampling, following the manufacturer’s instructions (reading at 15 min). RT-PCRs were carried out within 24 h of specimens’ collection. Out of 603 patients, 145 (24.05%) tested positive by RT-PCR and RAT and 451 (74.79%) tested negative by both methods; discordant results (RT-PCR+/RAT− or RT-PCR−/RAT+) were obtained in 7 patients (1.16%). RATs’ overall specificity and sensitivity were 96.03% (95%CI: 91.55–98.53%) and 99.78% (95%CI: 98.77–99.99%), respectively, taking RT-PCR as the reference. Overall, RAT negative predictive value was 98.69% (95%CI 97.17–99.40%). The GeneFinder COVID-19 Ag Plus Rapid Test performed well as a screening test for early diagnosis of COVID-19, especially in asymptomatic subjects. The data suggested that patients with RT-PCR-proven COVID-19 testing negative by RAT are unlikely to be infectious. GeneFinder COVID-19 Ag Plus Rapid Test also works on variants of concern (VOC) delta and omicron BA.1 and BA.2.