bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanodosimetric Calculations of Radiation-Induced DNA Damage in a New Nucleus Geometrical Model Based on the Isochore Theory
Authors: Thibaut Yann , Tang Nicolas , Tran Hoang Ngoc , Vaurijoux Aurélie , Villagrasa Carmen , Incerti Sébastien , Perrot Yann
Published: March 2022

Double-strand breaks (DSBs) in nuclear DNA represents radiation-induced damage that has been identified as particularly deleterious. Calculating this damage using Monte Carlo track structure modeling could be a suitable indicator to better assess and anticipate the side-effects of radiation therapy. However, as already demonstrated in previous work, the geometrical description of the nucleus and the DNA content used in the simulation significantly influence damage calculations. Therefore, in order to obtain accurate results, this geometry must be as realistic as possible. In this study, a new geometrical model of an endothelial cell nucleus and DNA distribution according to the isochore theory are presented and used in a Monte Carlo simulation chain based on the Geant4-DNA toolkit. In this theory, heterochromatin and euchromatin compaction are distributed along the genome according to five different families (L1, L2, H1, H2, and H3). Each of these families is associated with a different hetero/euchromatin rate related to its compaction level. In order to compare the results with those obtained using a previous nuclear geometry, simulations were performed for protons with linear energy transfers (LETs) of 4.29 keV/µm, 19.51 keV/µm, and 43.25 keV/µm. The organization of the chromatin fibers at different compaction levels linked to isochore families increased the DSB yield by 6–10%, and it allowed the most affected part of the genome to be identified. These new results indicate that the genome core is more radiosensitive than the genome desert, with a 3–8% increase in damage depending on the LET. This work highlights the importance of using realistic distributions of chromatin compaction levels to calculate radio-induced damage using Monte Carlo simulation methods.
Targeting of Proteins for Translocation at the Endoplasmic Reticulum
Authors: Pool Martin R.
Published: March 2022

The endoplasmic reticulum represents the gateway to the secretory pathway. Here, proteins destined for secretion, as well as soluble and membrane proteins that reside in the endomembrane system and plasma membrane, are triaged from proteins that will remain in the cytosol or be targeted to other cellular organelles. This process requires the faithful recognition of specific targeting signals and subsequent delivery mechanisms to then target them to the translocases present at the ER membrane, which can either translocate them into the ER lumen or insert them into the lipid bilayer. This review focuses on the current understanding of the first step in this process representing the targeting phase. Targeting is typically mediated by cleavable N-terminal hydrophobic signal sequences or internal membrane anchor sequences; these can either be captured co-translationally at the ribosome or recognised post-translationally and then delivered to the ER translocases. Location and features of the targeting sequence dictate which of several overlapping targeting pathway substrates will be used. Mutations in the targeting machinery or targeting signals can be linked to diseases.
A Liquid Biopsy-Based Approach for Monitoring Treatment Response in Post-Operative Colorectal Cancer Patients
Authors: Barták Barbara Kinga , Fodor Tamás , Kalmár Alexandra , Nagy Zsófia Brigitta , Zsigrai Sára , Szigeti Krisztina Andrea , Valcz Gábor , Igaz Péter , Dank Magdolna , Takács István , Molnár Béla
Published: March 2022

Monitoring the therapeutic response of colorectal cancer (CRC) patients is crucial to determine treatment strategies; therefore, we constructed a liquid biopsy-based approach for tracking tumor dynamics in non-metastatic (nmCRC) and metastatic (mCRC) patients (n = 55). Serial blood collections were performed during chemotherapy for measuring the amount and the global methylation pattern of cell-free DNA (cfDNA), the promoter methylation of SFRP2 and SDC2 genes, and the plasma homocysteine level. The average cfDNA amount was higher (p < 0.05) in nmCRC patients with recurrent cancer (30.4 ± 17.6 ng) and mCRC patients with progressive disease (PD) (44.3 ± 34.5 ng) compared to individuals with remission (13.2 ± 10.0 ng) or stable disease (12.5 ± 3.4 ng). More than 10% elevation of cfDNA from first to last sample collection was detected in all recurrent cases and 92% of PD patients, while a decrease was observed in most patients with remission. Global methylation level changes indicated a decline (75.5 ± 3.4% vs. 68.2 ± 8.4%), while the promoter methylation of SFRP2 and SDC2 and homocysteine level (10.9 ± 3.4 µmol/L vs. 13.7 ± 4.3 µmol/L) presented an increase in PD patients. In contrast, we found exact opposite changes in remission cases. Our study offers a more precise blood-based approach to monitor the treatment response to different chemotherapies than the currently used markers.
In Pancreatic Adenocarcinoma Alpha-Synuclein Increases and Marks Peri-Neural Infiltration
Authors: Bianchini Matteo , Giambelluca Maria , Scavuzzo Maria Concetta , Di Franco Gregorio , Guadagni Simone , Palmeri Matteo , Furbetta Niccolò , Gianardi Desirée , Costa Aurelio , Gentiluomo Manuel , Gaeta Raffaele , Pollina Luca Emanuele , Falcone Alfredo , Vivaldi Caterina , Di Candio Giulio , Biagioni Francesca , Busceti Carla Letizia , Soldani Paola , Puglisi-Allegra Stefano , Morelli Luca , Fornai Francesco
Published: March 2022

α-Synuclein (α-syn) is a protein involved in neuronal degeneration. However, the family of synucleins has recently been demonstrated to be involved in the mechanisms of oncogenesis by selectively accelerating cellular processes leading to cancer. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers, with a specifically high neurotropism. The molecular bases of this biological behavior are currently poorly understood. Here, α-synuclein was analyzed concerning the protein expression in PDAC and the potential association with PDAC neurotropism. Tumor (PDAC) and extra-tumor (extra-PDAC) samples from 20 patients affected by PDAC following pancreatic resections were collected at the General Surgery Unit, University of Pisa. All patients were affected by moderately or poorly differentiated PDAC. The amount of α-syn was compared between tumor and extra-tumor specimen (sampled from non-affected neighboring pancreatic areas) by using in situ immuno-staining with peroxidase anti-α-syn immunohistochemistry, α-syn detection by using Western blotting, and electron microscopy by using α-syn-conjugated immuno-gold particles. All the methods consistently indicate that each PDAC sample possesses a higher amount of α-syn compared with extra-PDAC tissue. Moreover, the expression of α-syn was much higher in those PDAC samples from tumors with perineural infiltration compared with tumors without perineural infiltration.
Telomere Targeting Approaches in Cancer: Beyond Length Maintenance
Authors: Vertecchi Eleonora , Rizzo Angela , Salvati Erica
Published: March 2022

Telomeres are crucial structures that preserve genome stability. Their progressive erosion over numerous DNA duplications determines the senescence of cells and organisms. As telomere length homeostasis is critical for cancer development, nowadays, telomere maintenance mechanisms are established targets in cancer treatment. Besides telomere elongation, telomere dysfunction impinges on intracellular signaling pathways, in particular DNA damage signaling and repair, affecting cancer cell survival and proliferation. This review summarizes and discusses recent findings in anticancer drug development targeting different “telosome” components.
Brain Metabolic Alterations in Alzheimer’s Disease
Authors: Ardanaz Carlos G. , Ramírez María J. , Solas Maite
Published: March 2022

The brain is one of the most energy-consuming organs in the body. Satisfying such energy demand requires compartmentalized, cell-specific metabolic processes, known to be complementary and intimately coupled. Thus, the brain relies on thoroughly orchestrated energy-obtaining agents, processes and molecular features, such as the neurovascular unit, the astrocyte–neuron metabolic coupling, and the cellular distribution of energy substrate transporters. Importantly, early features of the aging process are determined by the progressive perturbation of certain processes responsible for adequate brain energy supply, resulting in brain hypometabolism. These age-related brain energy alterations are further worsened during the prodromal stages of neurodegenerative diseases, namely Alzheimer’s disease (AD), preceding the onset of clinical symptoms, and are anatomically and functionally associated with the loss of cognitive abilities. Here, we focus on concrete neuroenergetic features such as the brain’s fueling by glucose and lactate, the transporters and vascular system guaranteeing its supply, and the metabolic interactions between astrocytes and neurons, and on its neurodegenerative-related disruption. We sought to review the principles underlying the metabolic dimension of healthy and AD brains, and suggest that the integration of these concepts in the preventive, diagnostic and treatment strategies for AD is key to improving the precision of these interventions.
In Silico Three-Dimensional (3D) Modeling of the SecY Protein of ‘Candidatus Phytoplasma Solani’ Strains Associated with Grapevine “Bois Noir” and Its Possible Relationship with Strain Virulence
Authors: Pierro Roberto , De Pascali Mariarosaria , Panattoni Alessandra , Passera Alessandro , Materazzi Alberto , De Bellis Luigi , Luvisi Andrea , Bianco Piero Attilio , Quaglino Fabio
Published: March 2022

Grapevine “bois noir”, related to the presence of ‘Candidatus Phytoplasma solani’ (‘Ca. P. solani’), represents a serious threat in several vine-growing areas worldwide. In surveys conducted over two years, mild and/or moderate symptoms and lower pathogen titer were mainly associated with ‘Ca. P. solani’ strains harboring a secY gene sequence variant (secY52), whereas severe symptoms and higher titer were mainly observed in grapevines infected by phytoplasma strains carrying any one of another four variants. A comparison of amino acid sequences of the protein SecY of ‘Ca. P. solani’ strains revealed the presence of conservative and semi-conservative substitutions. The deduced three-dimensional (3D) protein analysis unveiled that one semi-conservative substitution identified in the sequence variant secY52 is responsible for a structural disordered region that probably confers a flexibility for binding to distinct molecular complexes. In fact, the other analyzed variants show an organized structure and the 3D in silico prediction allowed the identification of β-sheets. Thus, differences in symptom severity and pathogen concentration observed in grapevines infected by ‘Ca. P. solani’ strains carrying distinct secY gene sequence variants suggest a possible relationship between SecY protein structure and phytoplasma strain virulence.
Multimodal Information Processing and Associative Learning in the Insect Brain
Authors: Thiagarajan Devasena , Sachse Silke
Published: March 2022

The study of sensory systems in insects has a long-spanning history of almost an entire century. Olfaction, vision, and gustation are thoroughly researched in several robust insect models and new discoveries are made every day on the more elusive thermo- and mechano-sensory systems. Few specialized senses such as hygro- and magneto-reception are also identified in some insects. In light of recent advancements in the scientific investigation of insect behavior, it is not only important to study sensory modalities individually, but also as a combination of multimodal inputs. This is of particular significance, as a combinatorial approach to study sensory behaviors mimics the real-time environment of an insect with a wide spectrum of information available to it. As a fascinating field that is recently gaining new insight, multimodal integration in insects serves as a fundamental basis to understand complex insect behaviors including, but not limited to navigation, foraging, learning, and memory. In this review, we have summarized various studies that investigated sensory integration across modalities, with emphasis on three insect models (honeybees, ants and flies), their behaviors, and the corresponding neuronal underpinnings.
Neonatal Neuroimaging in Neonatal Intensive Care Graduates Who Subsequently Develop Cerebral Palsy
Authors: Battin Malcolm R. , Williams Sîan A. , Mackey Anna , Alzaher Woroud , Sorhage Alexandra , Stott N. Susan
Published: March 2022

Cerebral palsy is a common cause of physical disability. The New Zealand Cerebral Palsy Register (NZCPR) was established in 2015 and reports national data. Internationally, an early CP diagnosis has been a focus, with imaging and clinical tools used to enable early accurate detection. Accordingly, guidelines are being developed for New Zealand, including a specific pathway for high-risk neonatal intensive care (NICU) graduates, reflecting the high rate of CP in this group. To inform this work, we reviewed imaging data from a retrospective NICU cohort identified from the NZCPR. In these 140 individuals with CP and a confirmed NICU admission during 2000–2019 inclusive, imaging frequency, modality, and rate of abnormality was determined. Overall, 114 (81.4%) had imaging performed in the NICU, but the frequency and modality used varied by gestational subgroup. For infants born at less than 32 weeks gestation, 53/55 had routine imaging with ultrasound, and IVH was graded as none or mild (grade 1–2) in 35 or severe (grade 3–4) in 18 infants. For the 34 infants born between 32–36 weeks gestation, only 13/19 imaged in the NICU were reported as abnormal. For 51 term-born infants, 41/42 imaged in the NICU with MRI had abnormal results.
Comparative Clinical Value of Pharmacologic Therapies for B-Cell Chronic Lymphocytic Leukemia: An Umbrella Analysis
Authors: Marchetti Monia , Rivela Paolo , Bertassello Claudia , Canicattì Manuela
Published: March 2022

Several new drugs are progressively improving the life span of patients with B-cell chronic lymphocytic leukemia (CLL). However, the rapidly evolving standard of care precludes robust assessments of the incremental clinical value of further innovative drugs. Therefore, we systematically reviewed comparative evidence on newly authorized CLL drugs, as reported by standard and network meta-analyses (MA) published since 2016. Overall, 17 MAs addressed the relative survival or safety of naïve and/or refractory/relapsed (R/R) CLL patients. In R/R patients, therapies including BTK- and BCL2-inhibitors reported progression free survival (PFS) hazard ratios ranging from 0.08 to 0.24 (versus chemotherapy) and a significant advantage in overall survival (OS). In naïve patients, the PFS hazard ratios associated with four recent chemo-free therapies (obinutuzumab- and/or acalabrutinib-based) ranged from 0.11 to 0.61 versus current standard treatments (STs), without a significant OS advantage. Ten MAs addressed the risk of cardiovascular, bleeding, and infective events associated with BTK inhibitors, with some reporting a different relative safety in naïve and R/R patients. In conclusion, last-generation therapies for CLL consistently increase PFS, but not OS, and minimally decrease safety, as compared with STs. Based on available evidence, the patient-customized adoption of new therapies, rather than universal recommendations, seems desirable in CLL patients.
NLRP3, NLRC4 and NLRC5 Gene Polymorphisms Associate with Susceptibility of Pulmonary Aspergillosis in Non-Neutropenic Patients
Authors: Zhong Jinjin , Liu Lulu , Lu Yajie , Gu Yu , Zhao Jiangnan , Chen Bilin , Zhou Wei , Su Xin
Published: March 2022

Background: Non-neutropenic pulmonary aspergillosis is one of the most common and serious fungal infections. Previous studies have shown that single nucleotide polymorphisms (SNPs) of pattern recognition receptors genes are associated with susceptibility to aspergillosis. NOD-like receptors (NLRs) play an important role in the immunological response against fungal infection. In this study, we investigated the relationship between polymorphisms of three NLRs and susceptibility to pulmonary aspergillosis disease in non-neutropenic patients. Methods: We included 73 patients with proven pulmonary aspergillosis and 103 healthy controls. A total of sixteen SNPs in the NLRP3, NLRC4, and NLRC5 genes were detected by PCR-direct sequencing. Then, we evaluated the association between these polymorphisms and susceptibility to aspergillosis. Results: Fifteen SNPs were consistent with Hardy–Weinberg equilibrium except for NLRP3 rs7525979. A total of eight SNPs (NLRP3 rs3806265, NLRC4 rs212704 and NLRC5 rs1684579, rs12598522, rs3995817, rs3995818, rs34531240, rs28438857) were observed an association with susceptibility of pulmonary aspergillosis. The CC homozygote of NLRP3 rs3806265, TT homozygote of NLRC5 rs1684579 and T allele of NLRC5 rs12598522 were associated with a higher risk of aspergillosis while TT homozygote of NLRC4 rs212704 was associated with a lower risk of aspergillosis. Especially in the invasive pulmonary aspergillosis subgroup, the TT homozygote of NLRC5 rs1684579 and rs3995817, the CC homozygote of NLRC5 rs34531240 and rs28438857, GG homozygote of NLRC5 rs3995818, the C allele and CC homozygote of NLRP3 rs3806265 were associated with higher susceptibility. Conclusions: This study showed an association between polymorphisms of NLRP3, NLRC4, and NLRC5 and susceptibility to pulmonary aspergillosis for the first time. Further investigations in larger populations are needed, and functional studies are also required to investigate the function of these NLRs in aspergillosis, as well as other fungal infection diseases.
Factors Influencing Immune Restoration in People Living with HIV/AIDS
Authors: Aksak-Wąs Bogusz Jan , Urbańska Anna , Scheibe Kaja , Serwin Karol , Leszczyszyn-Pynka Magdalena , Rafalska-Kosior Milena , Gołąb Joanna , Chober Daniel , Parczewski Miłosz
Published: March 2022

Introduction: Immune restoration is a key clinical aspect that is pursued in the care of human immunodeficiency virus (HIV)-infected patients. Despite effective antiretroviral treatment and undetectable viremia, immune recovery is often incomplete. Materials and methods: Data from 311 Caucasian patients were collected. SNP in CCR2(rs1799864), CX3CR1(rs3732378), HLAC-35(rs9264942), and CCR5(promoter, rs1799988); a 32bp deletion(Δ32) in CCR5; and HLA-B*5701 genotypes were correlated with clinical data and selected endpoints. Kaplan–Meier and Cox proportional hazards models were used to analyze the effects of genetic factors over time. Results: For HLA-B*5701, the effect on the CD4+/CD8+ >0.8 cell ratio was lost within 48 months (HR = 2.04, 95% CI: 1.04–4.03), and the effect on the CD4+ cell count >500 cells/µL was lost within 12 months (HR = 2.12, CI: 1.11–4.04). The effect of CCR2 GG on the CD4+/CD8+ >0.8 cell ratio was lost within 36 months (HR = 1.7, CI: 1.05–2.75). For CCR5 wt/Δ32, the effect on the CD4+/CD8+ >1.0 cell ratio was lost within 24 months (HR = 2.0, CI: 1.08–3.69), and the effect on the CD4+ >800 cells/µL cell count was lost within 18 months (HR = 1.98, CI: 1.14–4.73). Conclusions: Selected genetic polymorphisms, namely CCR2 GG and CCR5 Δ32, and the presence of the HLA-B*5701 allele positively influenced immune restoration in cART-treated patients with HIV/AIDS.
The Impact of the Age, Dyspnoea, and Airflow Obstruction (ADO) Index on the Medical Burden of Chronic Obstructive Pulmonary Disease (COPD)
Authors: Li Chin-Ling , Lin Mei-Hsin , Tsai Yuh-Chyn , Tseng Ching-Wan , Chang Chia-Ling , Shen Lien-Shi , Kuo Ho-Chang , Liu Shih-Feng
Published: March 2022

There are currently no good indicators that can be used to predict the medical expenses of chronic obstructive pulmonary disease (COPD). This was a retrospective study that focused on the correlation between the age, dyspnoea, and airflow obstruction (ADO) index and the Charlson comorbidity index (CCI) on the medical burden in COPD patients, specifically, those of patients with complete ADO index and CCI data in our hospital from January 2015 to December 2016. Of the 396 patients with COPD who met the inclusion criteria, 382 (96.5%) were male, with an average age of 71.3 ± 8.4 years. Healthcare resource utilisation was positively correlated with the ADO index. A significant association was found between the ADO index and CCI of COPD patients (p < 0.001). In-hospitalization expenses were positively correlated with the CCI (p < 0.001). Under the same CCI, the higher the ADO score, the higher the hospitalisation expenses. The ADO quartiles were positively correlated with the number of hospitalisations (p < 0.001), hospitalisation days (p < 0.001), hospitalisation expenses (p = 0.03), and total medical expenses (p = 0.037). Findings from this study show that the ADO index can predict the medical burden of COPD.
Associations between Phosphate Concentrations and Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation
Authors: Kim Beong Ki , Kim Chi Young , Kim Sua , Kim Yu Jin , Lee Seung Heon , Kim Je Hyeong
Published: March 2022

Phosphate concentrations change continuously throughout hospitalization; however, it is unclear which available phosphate measures are most clinically important for predicting hospital mortality. Therefore, we investigated phosphate concentrations in association with hospital mortality following admission to the intensive care unit. We retrospectively enrolled all adult patients receiving mechanical ventilation. Phosphate concentrations were divided into three categories: initially measured phosphate (iP); maximum–minimum phosphate values (ΔP); and phosphate arithmetic average (Pmean). In total, 175 patients were enrolled. The hospital mortality rate was 32.6%, and the most common primary diagnosis was respiratory failure. In multivariable logistic regression analyses, the odds ratios for hospital mortality in association with ΔP and Pmean values were 1.56 and 2.13, respectively (p < 0.0001). According to the obtained receiver operating characteristic curve, ΔP (0.75) and Pmean (0.72) each showed a fair predictive power for hospital mortality. In evaluating relative risks, we found that higher concentrations of Pmean and ΔP were each associated with a higher hospital mortality. ΔP and Pmean values were significantly associated with hospital mortality in critically ill patients, compared to iP. These findings showed that throughout hospitalization, it is important to reduce phosphate level fluctuations and maintain appropriate phosphate concentrations through consistent monitoring and corrections.
Multimorbidity Profile of COVID-19 Deaths in Portugal during 2020
Authors: Nogueira Paulo Jorge , de Araújo Nobre Miguel , Elias Cecília , Feteira-Santos Rodrigo , Martinho António C.-V. , Camarinha Catarina , Bacelar-Nicolau Leonor , Costa Andreia Silva , Furtado Cristina , Morais Liliane , Rachadell Juan , Pinto Mário Pereira , Pinto Fausto , Vaz Carneiro Antó
Published: March 2022

Background: COVID-19 is caused by SARS-CoV-2 infection and has reached pandemic proportions. Since then, several clinical characteristics have been associated with poor outcomes. This study aimed to describe the morbidity profile of COVID-19 deaths in Portugal. Methods: A study was performed including deaths certificated in Portugal with “COVID-19” (ICD-10: U07.1 or U07.2) coded as the underlying cause of death from the National e-Death Certificates Information System between 16 March and 31 December 2020. Comorbidities were derived from ICD-10 codes using the Charlson and Elixhauser indexes. The resident Portuguese population estimates for 2020 were used. Results: The study included 6701 deaths (death rate: 65.1 deaths/100,000 inhabitants), predominantly males (72.1). The male-to-female mortality ratio was 1.1. The male-to-female mortality rate ratio was 1.2; however, within age groups, it varied 5.0–11.4-fold. COVID-19 deaths in Portugal during 2020 occurred mainly in individuals aged 80 years or older, predominantly in public healthcare institutions. Uncomplicated hypertension, uncomplicated diabetes mellitus, congestive heart failure, renal failure, cardiac arrhythmias, dementia, and cerebrovascular disease were observed among COVID-19 deceased patients, with prevalences higher than 10%. A high prevalence of zero morbidities was registered using both the Elixhauser and Charlson comorbidities lists (above 40.2%). Nevertheless, high multimorbidity was also identified at the time of COVID-19 death (about 36.5%). Higher multimorbidity levels were observed in men, increasing with age up to 80 years old. Zero-morbidity prevalence and high multimorbidity prevalences varied throughout the year 2020, seemingly more elevated in the mortality waves’ peaks, suggesting variation according to the degree of disease incidence at a given period. Conclusions: This study provides detailed sociodemographic and clinical information on all certificated deaths from COVID-19 in Portugal during 2020, showing complex and extreme levels of morbidity (zero-morbidity vs. high multimorbidity) dynamics during the first year of the pandemic in Portugal.
Dynamical Sliding Mode Control for Robust Dynamic Positioning Systems of FPSO Vessels
Authors: Cho Seongpil , Shim Hyungwon , Kim Young-Shik
Published: March 2022

The conventional proportional derivative (PD) control algorithm with appropriate gain scheduling is generally applied to a dynamic positioning (DP) system. However, finding appropriate gains through gain scheduling makes the DP system more complicated. A sliding-mode control algorithm controls an arbitrary point, such as the turret system on a floating production storage and offloading (FPSO) vessel. This algorithm was developed for DP and can be applied to FPSO vessels considering the uncertainty of the vessel dynamics, unknown time-varying environmental disturbances, and transient performance. To control an arbitrary point on the FPSO vessel using a DP controller, the Jacobian matrix in the kinematic equation is modified to present the arbitrary point in the control. The Lyapunov stability theory is applied in the design of the SM control algorithm to provide robustness to the control system. A time-domain simulation tool was developed to verify the effectiveness of the proposed SM control algorithm. The performance of the control algorithm was evaluated numerically to address its efficacy. The results were compared with those obtained using the conventional PD control algorithm.
Effects of Seawater Acidification on Echinoid Adult Stage: A Review
Authors: Asnicar Davide , Marin Maria Gabriella
Published: March 2022

The continuous release of CO2 in the atmosphere is increasing the acidity of seawater worldwide, and the pH is predicted to be reduced by ~0.4 units by 2100. Ocean acidification (OA) is changing the carbonate chemistry, jeopardizing the life of marine organisms, and in particular calcifying organisms. Because of their calcareous skeleton and limited ability to regulate the acid–base balance, echinoids are among the organisms most threatened by OA. In this review, 50 articles assessing the effects of seawater acidification on the echinoid adult stage have been collected and summarized, in order to identify the most important aspects to consider for future experiments. Most of the endpoints considered (i.e., related to calcification, physiology, behaviour and reproduction) were altered, highlighting how various and subtle the effects of pH reduction can be. In general terms, more than 43% of the endpoints were modified by low pH compared with the control condition. However, animals exposed in long-term experiments or resident in CO2-vent systems showed acclimation capability. Moreover, the latitudinal range of animals’ distribution might explain some of the differences found among species. Therefore, future experiments should consider local variability, long-term exposure and multigenerational approaches to better assess OA effects on echinoids.
Innovations in the Integrated Management of Breast Cancer
Authors: Franceschini Gianluca , Sanchez Alejandro Martin , Mason Elena Jane , Masetti Riccardo
Published: March 2022

Breast cancer is commonly acknowledged as an international priority in healthcare [...]
Association of Elevated Expression Levels of COL4A1 in Stromal Cells with an Immunosuppressive Tumor Microenvironment in Low-Grade Glioma, Pancreatic Adenocarcinoma, Skin Cutaneous Melanoma, and Stomach Adenocarcinoma
Authors: Shin Hyo-Jae , Gil Minchan , Lee Im-Soon
Published: March 2022

Aberrant expression of collagen type IV alpha chain 1 (COL4A1) can influence tumor cell behavior. To examine the association of COL4A1 expression in the tumor microenvironment (TME) with tumor progression, we performed bioinformatics analyses of The Cancer Genome Atlas RNA sequencing and RNA microarray datasets available in public databases and identified upregulated COL4A1 expression in most examined tumor types compared to their normal counterparts. The elevated expression of COL4A1 was correlated with low survival rates of patients with low-grade glioma, pancreatic adenocarcinoma, skin cutaneous melanoma, and stomach adenocarcinoma, thus suggesting its potential use as a biomarker for the poor prognosis of these tumors. However, COL4A1 was mostly expressed in adjacent stromal cells, such as cancer-associated fibroblasts (CAFs) and endothelial cells. Additionally, COL4A1 expression was highly correlated with the signatures of CAFs and endothelial cells in all four tumor types. The expression of marker genes for the infiltration of pro-tumoral immune cells, such as Treg, M2, and TAM, and those of immunosuppressive cytokines exhibited very strong positive correlations with COL4A1 expression. Collectively, our data suggest that COL4A1 overexpression in stromal cells may be a potential regulator of tumor-supporting TME composition associated with poor prognosis.
Characterization of Depressive Symptom Trajectories in Women between Childbirth and Diagnosis
Authors: Chechko Natalia , Stickel Susanne , Losse Elena , Shymanskaya Aliaksandra , Habel Ute
Published: March 2022

The inhomogeneity of postpartum mood and mother–child attachment was estimated from immediately after childbirth to 12 weeks postpartum in a cohort of 598 young mothers. At 3-week intervals, depressed mood and mother–child attachment were assessed using the EPDS and the MPAS, respectively. The diagnosis was based on clinical interviews at the end of the 12-week follow-up. The latent class mixed model estimated multiple distinct patterns in depressed mood and mother–child attachment. The baseline EPDS cluster contained 72% of the study population and showed low EPDS values during the follow-up period, while the five remaining clusters showed either deterioration or improvement of the EPDS levels. The majority of women with postpartum depression showed deteriorating, and the majority of adjustment disorder cases improving, behavior. While the cases with more pronounced EPDS values were found to constitute more homogeneous clusters in terms of diagnosis, subclinical or only temporarily increased EPDS levels represented less homogeneous clusters. Higher EPDS levels correlated with the higher risk factor profiles. The four MPAS/EPDS clusters demonstrated that higher EPDS lead to lower mother–child attachment, and vice versa.
An Item Response Theory Analysis of the Wisconsin Card Sorting Test in Normal Aging, Alzheimer’s Disease and Parkinson’s Disease: Neurophysiological Approach
Authors: Sánchez-Rodríguez Juan Luis , Juárez-Vela Raúl , Santolalla-Arnedo Iván , Ruiz de Viñaspre-Hernandez Regina , Sánchez-González Juan Luis
Published: March 2022

The Wisconsin Card Sorting Test (WCST) is widely used to assess executive function, specifically mental flexibility. Item Response Theory (IRT) has several advantages over classical test theory, including the invariance of the measure. This study aimed to apply IRT to study the psychometric properties of WCST in control subjects and patients with idiopathic Parkinson’s disease (PD) and Alzheimer’s disease (AD). The sample consisted of 86 controls, 77 Parkinson’s disease subjects, and 155 AD subjects. The Rasch model was applied to binary data from the conversion to percentiles adjusted for age and schooling. The R program was used to calibrate the difficulty parameter. The characteristic curves of the items and the estimation of the difficulty parameter for each diagnostic group were obtained. WCST makes it possible to separate between different skill levels among the three diagnostic entities and its application may be useful for other neuropsychological tests. In conclusion, WCST has good clinical sensitivity and excellent discriminant validity in the groups under study, making it possible to separate them between different levels of ability or latent trait. Its application may be useful for other neuropsychological tests.
Hepatectomy or/with Metastatectomy for Recurrent Intrahepatic Cholangiocarcinoma: Of Promise for Selected Patients
Authors: Tsai Chun-Yi , Wang Shang-Yu , Chan Kun-Ming , Lee Wei-Chen , Chen Tse-Ching , Yeh Ta-Sen , Jan Yi-Yin , Yeh Chun-Nan
Published: March 2022

Introduction: Intrahepatic cholangiocarcinoma (ICC) has devastating outcomes owing to its advanced stage at diagnosis and high recurrence after hepatectomy. There is no preferred treatment for recurrent ICC. We retrospectively reviewed our patients who underwent repeated operations for recurrent ICCs based on their different indications to appraise the outcomes. Methods: In all, 160 out of 216 patients with ICC (71.4%) experienced recurrence after curative resection from 1977 to 2014. The patterns of recurrence were categorized according to the locations and numbers of recurrent tumors. Results: Patients with merely intrahepatic recurrence (n = 38) had superior overall survival (OS) compared with those with beyond intrahepatic recurrence (p < 0.0001). Twenty-seven out of 160 patients (16.8%) underwent repeat hepatectomy or/with metastatectomy for recurrence and had superior OS when compared to the remaining 133 patients who received nonoperative treatment/palliation (85.6 months versus 20.9 months, p < 0.001). Furthermore, patients suitable for repeat hepatectomy in the intrahepatic recurrent group (n = 12) had superior post-recurrence overall survival (PROS) than the remaining 26 patients receiving nonoperative treatment (61.6 months versus 14.7 months, p < 0.05). Conclusion: Liver is the most commonly involved site of recurrent ICC. However, merely intrahepatic recurrence may have a favorable prognosis compared to recurrence involving other sites. Aggressive hepatectomy may provide a survival benefit in selected patients.
The MAX Effect in an Oil Exporting Country: The Case of Norway
Authors: Kashif Muhammad , Leirvik Thomas
Published: March 2022

This paper assesses the effects of investors’ lottery-seeking behavior on expected returns in the Norwegian equity market, a relatively small equity market dominated by the energy industry. We use the MAX factor defined as maximum daily return over the previous month as the proxy of investors’ preference for lottery-like stocks. Despite evidence from recent literature that MAX has a negative relationship with the expected returns in other developed European markets, we find that the relationship is generally insignificant in Norway; however, it becomes more nuanced when we control for the state of the oil market. The dominance of firms related to the oil industry, which have experienced tremendous growth over the last couple of decades, masks the effect to a large extent. Conditional regressions show that the MAX effect is only significant in the Norwegian stock market when the oil market is in the bearish state.
Farmland Suitability Evaluation Oriented by Non-Agriculturalization Sensitivity: A Case Study of Hubei Province, China
Authors: Cui Xufeng , Zhou Tingting , Xiong Xinxing , Xiong Jiaqi , Zhang Jing , Jiang Yuehua
Published: March 2022

Farmland is one of the key factors affecting national or regional food security, and farmland suitability evaluation can provide critical information for the spatial layout of farmland. Previous studies have mainly focused on the role of natural factors in suitability evaluation, while ignoring the important influence of socio-economic activities. This study selects natural factors such as elevation and slope and non-agriculturalization sensitivity factors to build a farmland suitability evaluation framework of “natural non-agriculturalization sensitivity”, quantify the farmland suitability, and uses GIS technology to classify the evaluation results into four levels: highly, moderately, barely, and unsuitable. The results show that the non-agriculturalization sensitivity of farmland in Hubei Province shows the spatial characteristics of multi-point clustering, with density increasing from west and north to central and east; the overall farmland suitability in Hubei Province is high, and the areas of highly, moderately, barely, and unsuitable farmland account for 2.32%, 67.69%, 11.49%, and 18.50%, respectively. In terms of spatial distribution, there are obvious spatial differences in the farmland suitability, with highly and moderately suitable areas mainly distributed in the central and eastern regions and barely suitable and unsuitable areas mainly distributed in the western, northeastern, and southeastern parts of Hubei Province.
Borrowing Size and Urban Green Development Efficiency in the City Network of China: Impact Measures and Size Thresholds
Authors: Guo Aijun , Liu Peixian , Zhong Fanglei , Yang Chunlin , Luo Xijing
Published: March 2022

Cities enhance the efficiency of green development among themselves through their borrowing population, economic activities density and advanced functions, but the positive green effect of the borrowing size is affected by the city size. Using panel data of 280 prefecture-level cities in China for the period 2009–2019, this paper measures the borrowing size in three dimensions, namely the borrowing population size, borrowing economic activity density and borrowing advanced functions, and uses the super efficiency slacks-based measure (SBM) model, including non-desired outputs, to measure the urban green development efficiency. After that, this paper empirically examines the effect of the borrowing size on the urban green development efficiency in the Chinese urban network using a double-fixed-effect model. A panel threshold regression with city size as the threshold variable is conducted to evaluate the nonlinear relationship quantitatively between the borrowing size and urban green development efficiency. The results show that all three dimensions of the borrowing size have positive effects on the urban green development efficiency. There is a significant double-threshold effect between the borrowing size and urban green development efficiency; under the threshold of the city size, there is a U-shaped relationship between the borrowing population size, borrowing advanced functions and urban green development efficiency, whereas there is an inverted U-shaped relationship between the borrowing economic activity density and urban green development efficiency. Accordingly, this paper argues that government should pay attention to the role of the borrowing size in promoting urban green development efficiency and reasonably expand the city size.
Do Social Pension and Family Support Affect Farmers’ Land Transfer? Evidence from China
Authors: Li Zuojuan , Li Guofeng , Zhang Ke , Zhu Jingxin
Published: March 2022

The issues of farmers’ old-age security and land use have long been the focus of Chinese scholars’ and governmental attention. Land transfer plays a vital role in promoting agricultural scale operations, adjusting agricultural structures, and improving land utilization, while the old-age security function of land is one of the important factors affecting land transfer. Based on the data of the China Health and Retirement Longitudinal Study (CHARLS), this study uses the probit and structural equation models to explore social pension and family support mechanisms and pathways with regard to farmers’ land transfer. The results show that: (1) Social pension has a significant negative effect on farmers’ rent-out land, but a significant positive effect on rent-in land. Compared to farmers who do not participate in the New Rural Pension System (NRPS), the probability of rent-out land for farmers who participated in NRPS decreased by 2.44%, and rent-in land increased by 2.26%. (2) Family support has a significant positive effect on farmers’ rent-out land, but a negative effect on rent-in land. (3) Agricultural labor time plays a mediating role in the effect of social pension and family support on both farmers’ rent-out land and rent-in land.
Safety and Efficacy of Cone-Beam Computed Tomography-Guided Lung Tumor Localization with a Near-Infrared Marker: A Retrospective Study of 175 Patients
Authors: Chang Chia-Jung , Lu Chi-Hsuan , Gao Xing , Fang Hsin-Yueh , Chao Yin-Kai
Published: March 2022

Preoperative localization holds promise for overcoming the limitations of video-assisted thoracoscopic surgery (VATS) in the treatment of impalpable lung nodules. The purpose of this study was to assess the safety and efficacy of cone-beam computed tomography (CBCT)-guided localization using near-infrared (NIR) marking. Between 2017 and 2021, patients presenting with a solitary pulmonary nodule (SPN) who had undergone CBCT-guided lesion localization with indocyanine green (ICG) in a hybrid operating room were included. The primary outcomes were the efficacy of localization and the occurrence of complications. The study cohort consisted of 175 patients with the mean age of 58.76 years. The mean size and depth of the 175 SPNs were 8.34 mm and 5.3 mm, respectively. The mean time required for lesion marking was 14.71 min. Upon thoracoscopic inspection, the NIR tattoo was detected in the vast majority of the study participants (98.3%). An utility thoracotomy to allow digital palpation was required in two of the three patients in whom the tattoo was not identifiable. The perioperative survival rate was 100%, and the mean length of hospital stay was 3.09 days. We conclude that needle localization with ICG injection is a safe and feasible technique to localize SPNs prior to resection.
Membrane-Free Stem Cell Extract Enhances Blood–Brain Barrier Integrity by Suppressing NF-κB-Mediated Activation of NLRP3 Inflammasome in Mice with Ischemic Stroke
Authors: Ryu Ji Hyeon , Kim Yeonye , Kim Min Jae , Park Jisu , Kim Ji Won , Park Hye Sook , Kim Young Sil , Shin Hwa Kyoung , Shin Yong-Il
Published: March 2022

Membrane-free stem cell extract (MFSCE) of human adipose tissues possesses various biological activities. However, the effects of MFSCE on blood–brain barrier dysfunction and brain damage are unknown. In this study, we determined the role of MFSCE in an ischemic stroke mouse model. Mice were treated with MFSCE once daily for 4 days and 1 h before ischemic damage. Experimental ischemia was induced by photothrombosis. Pretreatment with MFSCE reduced infarct volume and edema and improved neurological, as well as motor functions. Evans blue leakage and water content in the brain tissue were reduced by MFSCE pretreatment relative to those in the vehicle group. MFSCE increased the expression of the tight junction proteins zonula occludens 1 and claudin-5, as well as vascular endothelial-cadherin, but decreased that of matrix metalloproteinase 9. Notably, MFSCE treatment decreased cell death and the level of NOD-like receptor protein 3 inflammasome, consistent with the downregulated expression of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 in the ischemic brain. These effects might have occurred via the suppression of the expression of Toll-like receptor 4 and activation of nuclear factor-κB. The results highlighted the potential of MFSCE treatment as a novel and preventive strategy for patients at a high risk of ischemic stroke.
The Effect of Low-Temperature Thermal Processing on Bovine Hydroxyapatite Bone Substitutes, toward Bone Cell Interaction and Differentiation
Authors: Porter Gemma Claire , Abdelmoneim Dina , Li Kai Chun , Duncan Warwick John , Coates Dawn Elizabeth
Published: March 2022

Ideal bone grafting scaffolds are osteoinductive, osteoconductive, and encourage osteogenesis through the remodeling processes of bone resorption, new bone formation, and successful integration or replacement; however, achieving this trifecta remains challenging. Production methods of bone grafts, such as thermal processing, can have significant effects on the degree of cell-surface interactions via wide-scale changes in the material properties. Here, we investigated the effects of small incremental changes at low thermal processing temperatures on the degree of osteoclast and osteoblast attachment, proliferation, and differentiation. Bovine bone scaffolds were prepared at 100, 130, 160, 190, and 220 °C and compared with a commercial control, Bio-Oss®. Osteoclast attachment and activity were significantly higher on lower temperature processed bone and were not present ≥190 °C. The highest osteoblast proliferation and differentiation were obtained from treatments at 130 and 160 °C. Similarly, qRT2-PCR assays highlighted osteoblasts attached to bone processed at 130 and 160 °C as demonstrating the highest osteogenic gene expression. This study demonstrated the significant effects of small-scale processing changes on bone graft materials in vitro, which may translate to a tailored approach of cellular response in vivo.
Effects of a ZnCuO-Nanocoated Ti-6Al-4V Surface on Bacterial and Host Cells
Authors: Dabbah Kamal , Perelshtein Ilana , Gedanken Aharon , Houri-Haddad Yael , Feuerstein Osnat
Published: March 2022

This study aims to investigate the effects of a novel ZnCuO nanoparticle coating for dental implants—versus those of conventional titanium surfaces—on bacteria and host cells. A multispecies biofilm composed of Streptococcus sanguinis, Actinomyces naeslundii, Porphyromonas gingivalis, and Fusobacterium nucleatum was grown for 14 days on various titanium discs: machined, sandblasted, sandblasted and acid-etched (SLA), ZnCuO-coated, and hydroxyapatite discs. Bacterial species were quantified with qPCR, and their viability was examined via confocal microscopy. Osteoblast-like and macrophage-like cells grown on the various discs for 48 h were examined for proliferation using an XTT assay, and for activity using ALP and TNF-α assays. The CSLM revealed more dead bacteria in biofilms grown on titanium than on hydroxyapatite, and less on sandblasted than on machined and ZnCuO-coated surfaces, with the latter showing a significant decrease in all four biofilm species. The osteoblast-like cells showed increased proliferation on all of the titanium surfaces, with higher activity on the ZnCuO-coated and sandblasted discs. The macrophage-like cells showed higher proliferation on the hydroxyapatite and sandblasted discs, and lower activity on the SLA and ZnCuO-coated discs. The ZnCuO-coated titanium has anti-biofilm characteristics with desired effects on host cells, thus representing a promising candidate in the complex battle against peri-implantitis.