bluuebunny/crossref_metadata_2025 huggingface dataset:
3D Cephalometric Normality Range: Auto Contractive Maps (ACM) Analysis in Selected Caucasian Skeletal Class I Age Groups
Authors: Farronato Marco , Baselli Giuseppe , Baldini Benedetta , Favia Gianfranco , Tartaglia Gianluca Martino
Published: May 2022

The objective of this paper is to define normal values of a novel 3D cephalometric analysis and to define the links through an artificial neural network (ANN). Methods: One hundred and fifteen CBCTs of Class I young patients, distributed among gender-adjusted developmental groups, were selected. Three operators identified 18 cephalometric landmarks from which 36 measurements were obtained. The repeatability was assessed through the ICC. Two-dimensional values were extracted by an automatic function, and the mean value and standard deviation were compared by paired Student’s t-tests. Correlation coefficient gave the relationships between 2D and 3D measurements for each group. The values were computed with the ANN to evaluate the parameters normality link and displayed by Pajek software. Results: The ICC assessed an excellent (≥0.9) repeatability. Normal values were extracted, and compared with 2D measurements, they showed a high correlation on the mid-sagittal plane, reaching 1.00, with the lowest 0.71 on the lateral plane. The ANN showed strong links between the values with the centrality of the go-sagittal plane compared to the rest. Conclusions: The study provides a set of 3D cephalometric values obtained by the upper and lower 95% CI for the mean divided into the developmental stage subgroups. The two-dimensional measurements showed variable concordance, while the ANN showed a centrality between the parameters.
Transcriptome Analysis of Plenodomus tracheiphilus Infecting Rough Lemon (Citrus jambhiri Lush.) Indicates a Multifaceted Strategy during Host Pathogenesis
Authors: Sicilia Angelo , Russo Riccardo , Caruso Marco , Arlotta Carmen , Di Silvestro Silvia , Gmitter Frederick G. , Gentile Alessandra , Nicolosi Elisabetta , Lo Piero Angela Roberta
Published: May 2022

The causal agent of mal secco disease is the fungus Plenodomus tracheiphilus, mainly affecting lemon tree survival in the Mediterranean area. Using a fully compatible host-pathogen interaction, the aim of our work was to retrieve the fungus transcriptome by an RNA seq approach during infection of rough lemon (Citrus jambhiri Lush.) to identify crucial transcripts for pathogenesis establishment and progression. A total of 2438 clusters belonging to P. tracheiphilus were retrieved and classified into the GO and KEGG categories. Transcripts were categorized mainly within the “membrane”, “catalytic activity”, and “primary metabolic process” GO terms. Moreover, most of the transcripts are included in the “ribosome”, “carbon metabolism”, and “oxidative phosphorylation” KEGG categories. By focusing our attention on transcripts with FPKM values higher than the median, we were able to identify four main transcript groups functioning in (a) fungus cell wall remodeling and protection, (b) destroying plant defensive secondary metabolites, (c) optimizing fungus development and pathogenesis, and (d) toxin biosynthesis, thus indicating that a multifaceted strategy to subdue the host was executed.
Chronic Inflammation Modulates Opioid Receptor Gene Expression and Triggers Respiratory Burst in a Teleost Model
Authors: Peixoto Diogo , Machado Marina , Azeredo Rita , Costas Benjamín
Published: May 2022

Stress-inducing husbandry and rearing conditions, bacterial infections or parasitic diseases may all lead to chronic inflammation. The immune response will then channel energy away from growth, reproduction and other important physiological processes, to fuel immune-related metabolic responses. The present study aims to unravel the mechanisms and contribute with new information on the molecular, cellular and humoral parameters of European seabass (Dicentrarchus labrax) undergoing chronic inflammation that can be used as health indicators for application in fish health management. European seabass individuals were intra-peritoneally injected with either Freund’s Incomplete Adjuvant (FIA) to induce inflammation or Hanks Balanced Salt Solution (HBSS) to serve as sham. Fish were sampled at 24 h, 7, 14 and 21 days post-injection and blood, plasma and head-kidney were collected. The results found were clear indicators of an inflamed peritoneal cavity and an ongoing systemic immune response that persisted for at least 21 days. Locally, inflammation was characterized by an intense recruitment of immune cells that was still evident 21 days after injection, thus illustrating the chronic character of the immune response. Cellular response was also noticed peripherally with leukocyte numbers rising in the blood of FIA-injected fish. Furthermore, the cellular-mediated respiratory burst peaked at 21 days post-FIA injection, suggesting that phagocytes were still actively fighting the phlogistic agent. Regarding the head-kidney molecular analysis, cxcr4 and il34 appear to be good markers of a chronic inflammation response due to their importance for pathways with high relevance in chronic inflammation settings. In addition, opioid receptor nopr seems to be a good marker of a chronic inflammation response due to its role in detecting noxious stimuli. The present study can serve as a baseline to assess long-term immune-related responses in future studies. For that, more research is nonetheless required to select more responsive and specific molecular markers.
Insulin-Like Growth Factor-Binding Protein 7 (IGFBP-7)—New Diagnostic and Prognostic Marker in Symptomatic Peripheral Arterial Disease?—Pilot Study
Authors: Szyszkowska Anna , Barańska Sylwia , Sawicki Robert , Tarasiuk Ewa , Dubatówka Marlena , Kondraciuk Marcin , Sawicka-Śmiarowska Emilia , Knapp Małgorzata , Głowiński Jerzy , Kamiński Karol , Lisowska Anna
Published: May 2022

The aim of our study was to evaluate the importance of insulin-like growth-factor-binding protein 7 (IGFBP-7) as a potential marker of symptomatic peripheral artery disease (PAD) occurrence. The study group consisted of 145 patients with diagnosed PAD, who qualified for the invasive treatment. The control group consisted of 67 individuals representing the local population and an ischemic heart disease (IHD) group of 88 patients after myocardial infarction or percutaneous coronary intervention. Patients with PAD had significantly higher IGFBP-7 concentrations than control group (1.80 ± 1.62 vs. 1.41 ± 0.45 ng/mL, p = 0.04). No significant differences between PAD patients and IHD patients were found (1.80 ± 1.62 vs. 1.76 ± 1.04 ng/mL, p = 0.783). Patients with multilevel PAD presented significantly higher IGFBP-7 concentrations than patients with aortoiliac PAD—median 1.18 (IQR 0.48–2.23) vs. 1.42 ng/mL (0.71–2.63), p = 0.035. In the group of patients who died or had a major adverse cardiovascular event (MACE) during six months of follow-up, a statistically significant higher IGFBP-7 concentration was found (median 2.66 (IQR 1.80–4.93) vs. 1.36 ng/mL (IQR 0.65–2.34), p = 0.004). It seems that IGFBP-7 is elevated in patients with atherosclerotic lesions—regardless of their locations. Further research should be conducted to verify IGFBP-7 usefulness as a predictor of MACE or death.
BMP4 Exerts Anti-Neurogenic Effect via Inducing Id3 during Aging
Authors: Li Tingting , Liu Hongmei , Jiang Dongfang , Yang Keyan , Shen Jiaqi , Feng Haiping , Wang Sijia , Zhang Yuxin , Wang Yun , Tang Tie-Shan
Published: May 2022

Bone morphogenetic protein (BMP) signaling has been shown to be intimately associated with adult neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ). Adult neurogenesis declines in aging rodents and primates. However, the role of BMP signaling in the age-related neurogenesis decline remains elusive and the effect of BMP4 on adult SVZ neurogenesis remains controversial. Here, the expression of BMP4 and its canonical effector phosphorylated-Smad1/5/8 (p-Smad1/5/8) in the murine SVZ and SGZ were found to be increased markedly with age. We identified Id3 as a major target of BMP4 in neuronal stem cells (NSCs) of both neurogenic regions, which exhibited a similar increase during aging. Intracerebroventricular infusion of BMP4 activated Smad1/5/8 phosphorylation and upregulated Id3 expression, which further restrained NeuroD1, leading to attenuated neurogenesis in both neurogenic regions and defective differentiation in the SGZ. Conversely, noggin, a potent inhibitor of BMP4, demonstrated opposing effects. In support of this, BMP4 treatment or lentiviral overexpression of Id3 resulted in decreased NeuroD1 protein levels in NSCs of both neurogenic regions and significantly inhibited neurogenesis. Thus, our findings revealed that the increased BMP4 signaling with age inhibited adult neurogenesis in both SVZ and SGZ, which may be attributed at least in part, to the changes in the Id3-NeuroD1 axis.
SERTAD1 Sensitizes Breast Cancer Cells to Doxorubicin and Promotes Lysosomal Protein Biosynthesis
Authors: Nguyen Hai Anh , Vu Son Hai , Jung Samil , Lee Beom Suk , Nguyen Thi Ngoc Quynh , Lee Hyojeong , Lee Hye-gyeong , Myagmarjav Davaajargal , Jo Taeyeon , Choi Yeongseon , Lee Myeong-Sok
Published: May 2022

Acquired chemoresistance of tumor cells is an unwanted consequence of cancer treatment. Overcoming chemoresistance is particularly important for efficiently improving cancer therapies. Here, using multiple lines of evidence, we report the suppressive role of SERTAD1 in apoptosis/anoikis. Among various breast cancer cell lines, higher SERTAD1 expression was found in MCF7 and MDA-MB-231 in suspension than in adherent cell culture. We revealed an unexpected phenomenon that different types of cell deaths were induced in response to different doses of doxorubicin (Dox) in breast cancer cells, presumably via lysosomal membrane permeabilization. A low dose of Dox highly activated autophagy, while a high dose of the chemotherapy induced apoptosis. Inhibition of SERTAD1 promoted the sensitivity of breast cancer cells to Dox and paclitaxel, leading to a significant reduction in tumor volumes of xenograft mice. Simultaneously targeting cancer cells with Dox and autophagy inhibition successfully induced higher apoptosis/anoikis. The novel role of SERTAD1 in maintaining cellular homeostasis has also been suggested in which lysosomal contents, including LAMP1, LAMP2, CTSB, and CTSD, were reduced in SERTAD1-deficient cells.
Amyloid Beta Oligomers-Induced Ca2+ Entry Pathways: Role of Neuronal Networks, NMDA Receptors and Amyloid Channel Formation
Authors: Caballero Erica , Hernando-Pérez Elena , Tapias Victor , Calvo-Rodríguez María , Villalobos Carlos , Núñez Lucía
Published: May 2022

The molecular basis of amyloid toxicity in Alzheimer’s disease (AD) remains controversial. Amyloid β (Aβ) oligomers promote Ca2+ influx, mitochondrial Ca2+ overload and apoptosis in hippocampal neurons in vivo and in vitro, but the primary Ca2+ entry pathways are unclear. We studied Ca2+ entry pathways induced by Aβ oligomers in rat hippocampal and cerebellar neurons. Aβ oligomers induce Ca2+ entry in neurons. Ca2+ responses to Aβ oligomers are large after synaptic networking and prevented by blockers of synaptic transmission. In contrast, in neurons devoid of synaptic connections, Ca2+ responses to Aβ oligomers are small and prevented only by blockers of amyloid channels (NA7) and NMDA receptors (MK801). A combination of NA7 and MK801 nearly abolished Ca2+ responses. Non-neuronal cells bearing NMDA receptors showed Ca2+ responses to oligomers, whereas cells without NMDA receptors did not exhibit Ca2+ responses. The expression of subunits of the NMDA receptor NR1/ NR2A and NR1/NR2B in HEK293 cells lacking endogenous NMDA receptors restored Ca2+ responses to NMDA but not to Aβ oligomers. We conclude that Aβ oligomers promote Ca2+ entry via amyloid channels and NMDA receptors. This may recruit distant neurons intertwisted by synaptic connections, spreading excitation and recruiting further NMDA receptors and voltage-gated Ca2+ channels, leading to excitotoxicity and neuron degeneration in AD.
Solving Color Reproducibility between Digital Devices: A Robust Approach of Smartphones Color Management for Chemical (Bio)Sensors
Authors: Cebrián Pablo , Pérez-Sienes Leticia , Sanz-Vicente Isabel , López-Molinero Ángel , de Marcos Susana , Galbán Javier
Published: May 2022

In the past twelve years, digital image colorimetry (DIC) on smartphones has acquired great importance as an alternative to the most common analytical techniques. This analysis method is based on fast, low-cost, and easily-accessible technology, which can provide quantitative information about an analyte through the color changes of a digital image. Despite the fact that DIC is very widespread, it is not exempt from a series of problems that are not fully resolved yet, such as variability of the measurements between smartphones, image format in which color information is stored, power distribution of the illuminant used for the measurements, among others. This article proposes a methodology for the standardization and correction of these problems using self-developed software, together with the use of a 3D printed light box. This methodology is applied to three different colorimetric analyses using different types and brands of smartphones, proving that comparable measurements between devices can be achieved. As color can be related to many target analytes, establishing this measurement methodology can lead to new control analysis applicable to diverse sectors such as alimentary, industrial, agrarian, or sanitary.
Antidepressant-like Effects of Renin Inhibitor Aliskiren in an Inflammatory Mouse Model of Depression
Authors: Alzarea Sami I. , Alhassan Hassan H. , Alzarea Abdulaziz I. , Al-Oanzi Ziad H. , Afzal Muhammad
Published: May 2022

Depression is considered a neuropsychic disease that has global prevalence and is associated with disability. The pathophysiology of depression is not well understood; however, emerging evidence has indicated that neuroinflammation could contribute to developing depression symptoms. One of the factors that have a role in the development of neuroinflammation is the renin–angiotensin system. Therefore, the goal of the current study is to determine the antidepressant-like effects of Aliskiren, a renin inhibitor, against lipopolysaccharide (LPS)-induced depressive-like behavior in mice, glial cell activation, and the upregulation of proinflammatory cytokines in the prefrontal cortex. For behavioral studies, the open field test (OFT), tail suspension test (TST), forced swim test (FST), and sucrose preference test (SPT) were used. Inflammatory markers were assessed using real-time polymerase chain reaction (RT-PCR). LPS administration (0.5 mg/kg, intraperitoneal injection (i.p.)) sufficiently reduced the number of crossings in OFT, whereas Aliskiren pretreatment (10 mg/kg, i.p.) attenuated the LPS effect for two hours after LPS injection. The treatments did not show effects on locomotor activity in OFT 24 h after LPS administration. LPS increased the immobility time in TST and FST or reduced sucrose consumption in SPT after 24 h. Aliskiren reversed the effects induced by LPS in TST, FST, and SPT. CD11 b mRNA, a microglial marker, GFAP mRNA, an astroglial marker, and proinflammatory cytokines genes (TNF-α, IL-1β, and IL-6) were upregulated in the prefrontal cortex in LPS exposed animals. However, Aliskiren reduced LPS-induced inflammatory genes in the prefrontal cortex. Hence, the outcomes conclude that Aliskiren prevents depressive illness associated with neuroinflammation in humans.
Anxiety and Sleep Quality Amelioration in College Students: A Comparative Study between Team Sports and Individual Sports
Authors: Ji Chaoxin , Yang Jun , Lin Lin , Chen Song
Published: May 2022

Background: Anxiety is one of the most common mental disorders and is often accompanied by sleep disturbances. Studies have focused on the ameliorative effect of sports games on anxiety and its subsidiary issues. However, the effect on the improvement of such mental and physical disorders between individual sports and team group sports is not yet clear, especially regarding their effects on anxiety and sleep quality improvement. Therefore, this paper explores the improvement effects of individual sports and team sports participation on anxiety symptoms and sleep quality amelioration. Objective: To explore the effects of individual and team group sports participation on ameliorating college students’ anxiety symptoms and sleep quality. Methods: A total of 197 college students were sampled in the study. The self-rating anxiety scale (SAS) and Pittsburgh sleep quality index (PSQI) were used to assess the severity of anxiety symptoms and level of sleep quality. Participants were randomly divided into three groups: team sports, individual sports, and control groups. The distribution ratio of these groups was 1:1:1. Results: Generally, compared with the control group, the subjects in the team sports group and individual sports group had greater improvements in anxiety amelioration and sleep quality improvements. Specifically, the improvement effect between individual and team sports groups was different. To assess the resulting differences, improvements in anxiety symptoms and sleep quality were compared between the team sports group and the individual sports group with reference to the mean change in the control group. In the corrected model, the odds advantage ratio (OR) of anxiety symptom improvement after individual sports was 3.18 (CI 2.87–11.21), and the advantage OR of anxiety symptom improvement after team sports was 4.99 (CI 4.06–14.87). The advantage OR of sleep quality improvement after individual sports was 7.32 (CI 5.53–18.22), and the advantage OR of anxiety symptom improvement after team sports was 7.98 (CI 6.69–19.98). Conclusion: After 6 weeks of intervention, it was found that both team sports and individual sports improved anxiety symptoms and sleep quality with different effects. Team sports were better at improving anxiety, while individual sports and team sports shared the same improvement effect with no significant difference in sleep quality improvement.
Learning Environment Design and Use
Authors: Woolner Pamela , Cardellino Paula
Published: May 2022

Reflecting a global trend of increased school construction, research into the built environment of education has multiplied over the last two decades [...]
Vision-Based Methods for Relative Sag Measurement of Suspension Bridge Cables
Authors: Huang Can , Wang Yongwei , Xu Shuyuan , Shou Wenchi , Peng Chengming , Lv Danfeng
Published: May 2022

Main cables, comprising a number of wire strands, constitute a vital element in long-span suspension bridges. The determination of their alignment during construction is of great importance, and relative sag is commonly measured for the efficient sag adjustment of general strands. The conventional approach uses the caterpillar method, which is inconvenient, difficult-to-implement, and potentially dangerous. In order to realize the high-precision measurement of cable alignment in a strong wind environment, a vision-based method for relative sag measurement of the general cable strands is proposed in this paper. In the proposed measurement system, images of pre-installed optical targets are collected and analyzed to realize the remote, automatic, and real-time measurement of the relative sag. The influences of wind-induced cable shaking and camera shaking on the accuracy of the height difference measurement are also theoretically analyzed. The results show that cable strand torsion and camera roll have a great impact on the measurement accuracy, while the impacts of the cable strand swing and vibration, camera swing and vibration, and camera pitch and yaw are insignificant. The vision-based measurement system tested in the field experiment also shows a measurement error within 3 mm, which meets the requirements for cable adjustment construction. At the same time, the vision-based measurement method proposed and validated in this paper can improve the measurement accuracy and efficiency of strand alignment in a strong wind environment. Potential risks involved in the manual measurement, e.g., working at heights and in strong wind environments, can be eliminated, facilitating the automation of the cable erection process.
Adverse Events in 1406 Patients Receiving 13,780 Cycles of Azacitidine within the Austrian Registry of Hypomethylating Agents—A Prospective Cohort Study of the AGMT Study-Group
Authors: Leisch Michael , Pfeilstöcker Michael , Stauder Reinhard , Heibl Sonja , Sill Heinz , Girschikofsky Michael , Stampfl-Mattersberger Margarete , Tinchon Christoph , Hartmann Bernd , Petzer Andreas , Schreder Martin , Kiesl David , Vallet Sonia , Egle Alexander , Melchardt Thomas , Piringer Gudrun , Zebisch Armin , Machherndl-Spandl Sigrid , Wolf Dominik , Keil Felix , Drost Manuel , Greil Richard , Pleyer Lisa
Published: May 2022

Background: Azacitidine is the treatment backbone for patients with acute myeloid leukemia, myelodysplastic syndromes and chronic myelomonocytic leukemia who are considered unfit for intensive chemotherapy. Detailed reports on adverse events in a real-world setting are lacking. Aims: To analyze the frequency of adverse events in the Austrian Registry of Hypomethylating agents. To compare real-world data with that of published randomized clinical trials. Results: A total of 1406 patients uniformly treated with a total of 13,780 cycles of azacitidine were analyzed. Hematologic adverse events were the most common adverse events (grade 3–4 anemia 43.4%, grade 3–4 thrombopenia 36.8%, grade 3–4 neutropenia 36.1%). Grade 3–4 anemia was significantly more common in the Registry compared to published trials. Febrile neutropenia occurred in 33.4% of patients and was also more common in the Registry than in published reports. Other commonly reported adverse events included fatigue (33.4%), pain (29.2%), pyrexia (23.5%), and injection site reactions (23.2%). Treatment termination due to an adverse event was rare (5.1%). Conclusion: The safety profile of azacitidine in clinical trials is reproducible in a real-world setting. With the use of prophylactic and concomitant medications, adverse events can be mitigated and azacitidine can be safely administered to almost all patients with few treatment discontinuations.
Mechanism and Management of Checkpoint Inhibitor-Related Toxicities in Genitourinary Cancers
Authors: Li Haoran , Sahu Kamal K. , Maughan Benjamin L.
Published: May 2022

The use of immune checkpoint inhibitors (ICIs) is rapidly increasing as more combinations and clinical indications are approved in the field of genitourinary malignancies. Most immunotherapeutic agents being approved are for the treatment of renal cell carcinoma and bladder cancer, which mainly involve PD-1/PD-L1 and CTLA-4 pathways. There is an ongoing need for recognizing and treating immunotherapy-related autoimmune adverse effects (irAEs). This review aims to critically appraise the recent literature on the mechanism, common patterns, and treatment recommendations of irAEs in genitourinary malignancies. We review the epidemiology of these adverse effects as well as general treatment strategies. The underlying mechanisms will also be discussed. Diagnostic considerations including differential diagnosis are also included in this review.
T-DM1 after Pertuzumab plus Trastuzumab: Treatment Sequence-Induced Selection Bias in HER2-Positive Metastatic Breast Cancer
Authors: Sanglier Thibaut , Fabi Alessandra , Flores Carlos , Flahavan Evelyn M. , Pena-Murillo Claudia , Meyer Anne-Marie , Montemurro Filippo
Published: May 2022

Real-world studies have suggested decreased trastuzumab emtansine (T-DM1) effectiveness in patients with metastatic breast cancer (mBC) who received prior trastuzumab plus pertuzumab (H + P). However, these studies may have been biased toward pertuzumab-experienced patients with more aggressive disease. Using an electronic health record-derived database, patients diagnosed with mBC on/after 1 January 2011 who initiated T-DM1 in any treatment line (primary cohort) or who initiated second-line T-DM1 following first-line H ± P (secondary cohort) from 22 February 2013 to 31 December 2019 were included. The primary outcome was time from index date to next treatment or death (TTNT). In the primary cohort (n = 757), the percentage of patients with prior P increased from 37% to 73% across the study period, while population characteristics and treatment effectiveness measures were generally stable. Among P-experienced patients from the secondary cohort (n = 246), median time from mBC diagnosis to T-DM1 initiation increased from 10 to 14 months (2013–2019), and median TTNT increased from 4.4 to 10.2 months (2013–2018). Over time, prior H + P prevalence significantly increased with no observable impact on T-DM1 effectiveness. Drug approval timing should be considered when assessing treatment effectiveness within a sequence.
Local and Regional Therapies for Hepatocellular Carcinoma and Future Combinations
Authors: Hatzidakis Adam , Müller Lukas , Krokidis Miltiadis , Kloeckner Roman
Published: May 2022

Background: Hepatocellular carcinoma (HCC) can be treated by local and regional methods of percutaneous interventional radiological techniques. Indications depend on tumor size, type and stage, as well as patient’s condition, liver function and co-morbidities. According to international classification systems such as Barcelona Clinic Liver Cancer (BCLC) classification, very early, early or intermediate staged tumors can be treated either with ablative methods or with transarterial chemoembolization (TACE), depending on tumor characteristics. The combination of both allows for individualized forms of treatment with the ultimate goal of improving response and survival. In recent years, a lot of research has been carried out in combining locoregional approaches with immune therapy. Although recent developments in systemic treatment, especially immunotherapy, seem quite promising and have expanded possible combined treatment options, there is still not enough evidence in their favor. The aim of this review is to provide a comprehensive up-to-date overview of all these techniques, explaining indications, contraindications, technical problems, outcomes, results and complications. Moreover, combinations of percutaneous treatment with each other or with immunotherapy and future options will be discussed. Use of all those methods as down-staging or bridging solutions until surgery or transplantation are taken into consideration will also be reviewed. Conclusion: Local and regional therapies remain a mainstay of curative and palliative treatment of patients with HCC. Currently, evidence on potential combination of the local and regional treatment options with each other as well as with other treatment modalities is growing and has the potential to further individualize HCC therapy. To identify the most suitable treatment option out of these new various options, a repeated interdisciplinary discussion of each case by the tumor board is of utmost importance.
Tumour Size and T-Stage in Pancreatic Cancer Resection Specimens Depend on the Pathology Examination Approach
Authors: Tran My Linh , Holm Maia Blomhoff , Verbeke Caroline Sophie
Published: May 2022

In the eighth edition of the TNM classification for pancreatic ductal adenocarcinoma (PDAC), stages T1 to T3 are defined by tumour size, size measurement being deemed objective and accurate. This study investigated whether various, currently used approaches to tumour measurement result in different tumour sizes and differences in T-stage assignment. In a series of 315 resected PDAC, tumour sizes were measured as follows: macroscopically in a single or in two perpendicular planes and with or without microscopic corroboration. Comparison of the resulting tumour sizes showed that both macroscopic measurement in two planes and microscopic corroboration gave significantly different results (p < 0.001). Compared to the most simple approach (macroscopic measurement in one plane), the comprehensive approach (macroscopic measurement in two planes with microscopic corroboration) resulted in a larger tumour size in 263 (83%) cases (mean absolute size difference: 10 mm; mean relative size change: 36%). T-stage assignment differed in 142 (45%) cases between the simple and comprehensive approach and affected 87%, 38% and 48% of the cases deemed to be stage T1, T2 and T3, respectively. In conclusion, tumour size and T-stage are highly approach-dependent. Consensus on an accurate method is required to ensure comparability of these basic data.
Behind the Wall—Compartment-Specific Neovascularisation during Post-Stroke Recovery in Mice
Authors: Kolbinger Anja , Kestner Roxane Isabelle , Jencio Lara , Schäufele Tim J. , Vutukuri Rajkumar , Pfeilschifter Waltraud , Scholich Klaus
Published: May 2022

Ischemic stroke is a highly prevalent vascular disease leading to oxygen- and glucose deprivation in the brain. In response, ischemia-induced neovascularization occurs, which is supported by circulating CD34+ endothelial progenitor cells. Here, we used the transient middle cerebral artery occlusion (tMCAO) mouse model to characterize the spatio-temporal alterations within the ischemic core from the acute to the chronic phase using multiple-epitope-ligand cartography (MELC) for sequential immunohistochemistry. We found that around 14 days post-stroke, significant angiogenesis occurs in the ischemic core, as determined by the presence of CD31+/CD34+ double-positive endothelial cells. This neovascularization was accompanied by the recruitment of CD4+ T-cells and dendritic cells as well as IBA1+ and IBA1− microglia. Neighborhood analysis identified, besides pericytes only for T-cells and dendritic cells, a statistically significant distribution as direct neighbors of CD31+/CD34+ endothelial cells, suggesting a role for these cells in aiding angiogenesis. This process was distinct from neovascularization of the peri-infarct area as it was separated by a broad astroglial scar. At day 28 post-stroke, the scar had emerged towards the cortical periphery, which seems to give rise to a neuronal regeneration within the peri-infarct area. Meanwhile, the ischemic core has condensed to a highly vascularized subpial region adjacent to the leptomeningeal compartment. In conclusion, in the course of chronic post-stroke regeneration, the astroglial scar serves as a seal between two immunologically active compartments—the peri-infarct area and the ischemic core—which exhibit distinct processes of neovascularization as a central feature of post-stroke tissue remodeling. Based on our findings, we propose that neovascularization of the ischemic core comprises arteriogenesis as well as angiogenesis originating from the leptomenigeal vasculature.
Metabolic Reprogramming of Innate Immune Cells as a Possible Source of New Therapeutic Approaches in Autoimmunity
Authors: Mohammadnezhad Leila , Shekarkar Azgomi Mojtaba , La Manna Marco Pio , Sireci Guido , Rizzo Chiara , Badami Giusto Davide , Tamburini Bartolo , Dieli Francesco , Guggino Giuliana , Caccamo Nadia
Published: May 2022

Immune cells undergo different metabolic pathways or immunometabolisms to interact with various antigens. Immunometabolism links immunological and metabolic processes and is critical for innate and adaptive immunity. Although metabolic reprogramming is necessary for cell differentiation and proliferation, it may mediate the imbalance of immune homeostasis, leading to the pathogenesis and development of some diseases, such as autoimmune diseases. Here, we discuss the effects of metabolic changes in autoimmune diseases, exerted by the leading actors of innate immunity, and their role in autoimmunity pathogenesis, suggesting many immunotherapeutic approaches.
A New Benzoxazole-Based Fluorescent Macrocyclic Chemosensor for Optical Detection of Zn2+ and Cd2+
Authors: Paderni Daniele , Giorgi Luca , Voccia Maria , Formica Mauro , Caporaso Lucia , Macedi Eleonora , Fusi Vieri
Published: May 2022

Background: Benzoxazole-containing ligands find many applications both in medicinal chemistry, catalysis and fluorescence chemosensing. Benzoxazole-containing macrocycles could be therefore a good strategy to achieve stable and selective fluorescent complexes with suitable metal ions. In this work, the synthesis, binding, and photochemical properties of a new fluorescent ligand (L) are reported. L is a cyclophane macrocycle containing the 1,3-bis(benzo[d]oxazol-2-yl)phenyl (BBzB) fluorophore and an aliphatic tetra-amine chain to form the macrocyclic skeleton. Methods: Spectrophotometric and spectrofluorimetric measurements, 1H NMR analysis, and DFT calculations were performed. Results: L behaves as a PET-mediated chemosensor, being emissive at 390 nm at acidic pH and non-emissive at basic pH. The chemosensor is able to detect Zn2+ and Cd2+ in an aqueous medium (acetonitrile–water, 4:1 v/v) at neutral pH through a CHEF effect upon metal ion coordination. Paramagnetic metal ions (Cu2+) and heavy atoms (Pb2+, Hg2+) resulted in a quenching of fluorescence or very low emission. Conclusions: The new cyclophane macrocycle L was revealed to be a selective PET-regulated chemosensor for Zn2+ and Cd2+ in an aqueous medium, being able to bind up to two and one metal cations, respectively. The molecule showed a shifted emission towards the visible region compared to similar systems, suggesting a co-planar conformation of the aromatic fragment upon metal coordination. All these data are supported by both experimental measurements and theoretical calculations.
The Role of Cognitive Skills, Sex, and Parental Education for Social–Emotional Skills: A Cross-Sectional Study on the WPPSI-IV Performances of Children Aged 3 to 5 Years
Authors: Walter Franziska , Daseking Monika , Pauls Franz
Published: May 2022

Background: Current research suggests that knowledge about the relationship between cognition and social–emotional skills in preschoolers is important to better understand child development. The present study investigated possible effects of cognitive skills measured by the Wechsler Primary and Preschool Scale—Fourth Edition (WPPSI-IV), children’s sex, and parental educational level on social–-emotional skills measured by the Developmental Test 6 Months to 6 Years—Revision (ET 6-6 R) for children aged 3 to 5. Methods: Statistical analyses were based on a sample of N = 93 children (47 females, 46 males). First, bivariate correlations among relevant WPPSI-IV index scores, the ET social–emotional quotient, children’s sex, and parental educational level were calculated to identify possible significant associations between the variables under investigation. Subsequently, two multiple regression analyses were conducted to test for the hypothesized main effects of cognitive skills, children’s sex, and parental educational level on social–emotional skills. Finally, a moderated multiple regression analysis was carried out to investigate whether possible effects of cognitive skills on social–emotional skills were moderated by children’s sex and parental educational level. Results: Regression analyses indicated that visual–spatial skills measured by the WPPSI-IV and children’s sex have both a small but significant main effect on social–emotional skills. The main effect of sex was due to the fact that, on average, females achieved higher scores on the measure of social–emotional skills than males. Conclusions: The present findings suggest that the WPPSI-IV represents a suitable test battery for the assessment of those cognitive skills, which might play a reasonable role in social–emotional development
Antigenotoxic Effect of Ascorbic Acid and Resveratrol in Erythrocytes of Ambystoma mexicanum, Oreochromis niloticus and Human Lymphocytes Exposed to Glyphosate
Authors: Alvarez-Moya Carlos , Sámano-León Alexis Gerardo , Reynoso-Silva Mónica , Ramírez-Velasco Rafael , Ruiz-López Mario Alberto , Villalobos-Arámbula Alma Rosa
Published: May 2022

Glyphosate is a controversial herbicide. Its genotoxicity and presence in various ecosystems have been reported. The use of ascorbic acid and resveratrol could protect different organisms from glyphosate-induced genetic damage. In the present study, specific genetic damage induced by glyphosate was evaluated in erythrocytes of Oreochromis niloticus, Ambystoma mexicanum and human lymphocytes. Simultaneously, the antigenotoxic capacity of various concentrations of ascorbic acid and resveratrol was evaluated by means of pretreatment and simultaneous treatment protocols. The 0.03, 0.05 and 0.07 mM concentrations of glyphosate induced significant genotoxic activity (p < 0.05) in human lymphocytes and in erythrocytes of the species studied, and could cause genomic instability in these populations. The reduction in genetic damage observed in human lymphocytes exposed to high concentrations of glyphosate is only apparent: excessive genetic damage was associated with undetectable excessive tail migration length. A significant (p < 0.05) antigenotoxic effect of ascorbic acid and resveratrol was observed in all concentrations, organisms and protocols used. Both ascorbic acid and resveratrol play an important role in maintaining the integrity of DNA. Ascorbic acid in Oreochromis niloticus, Ambystoma mexicanum reduced glyphosate-induced genetic damage to a basal level. Therefore, our data indicate that these antioxidants could help preserve the integrity of the DNA of organisms exposed to glyphosate. The consumption of antioxidants is a useful tool against the genotoxicity of glyphosate.
Dual-Band Terahertz Perfect Absorber Based on Metal Micro-Nano Structure
Authors: Guan Zehai , Liu Yanxiu , Li Ye , Zhao Peng , Zhang Yubin , Jiang Sheng
Published: May 2022

We propose a sub-wavelength range-based dual-band tunable ideal terahertz metamaterial perfect absorber. The absorber structure consists of three main layers, with the absorber layer consisting of a metal I-shaped structure. By simulating the incident wave absorbance of the structure, we found that the structure has more than 99% absorption peaks in both bands. In addition, we have investigated the relationship between structural absorbance and the structural geometrical parameters. We have studied the relationship between the thickness of the metal absorber layer hb and the absorbance of the metamaterial structure in the 4–14 THz band. Secondly, we have studied the relationship between the thickness of the SiO2 dielectric layer and structural absorbance. Afterwards, we have studied the relationship between the incident angle of the incident electromagnetic wave and structural absorbance. Finally, we have studied the relationship between the length of the metal structure and structural absorbance. The structure can be effectively used for detectors, thermal emitters, terahertz imaging and detection.
The Effect on Energy Efficiency of Yttria-Stabilized Zirconia on Brass, Copper and Hardened Steel Nozzle in Additive Manufacturing
Authors: Demir Hasan , Cosgun Atıl Emre
Published: May 2022

This study aimed to investigate if a thermal barrier coating (TBC) affected the energy efficiency of 3D printers. In accordance with this purpose, the used TBC technique is clearly explained and adapted to a nozzle in a simulation environment. Brass, copper, and hardened steel were selected to be the materials for the nozzles. The reason for the usage of a thermal barrier coating method is that the materials are made with low thermal conductivity, which reduces the thermal conductivity and energy losses. Yttria-stabilized zirconia was used to coat material on brass, copper, and hardened steel. To prevent temperature fluctuations, yttria-stabilized zirconia together with a NiCRAl bond layer was used and, thus, heat loss was prevented. Additionally, the paper addressed the effects of the coating on the average heat flux density and the average temperature of the nozzles. In addition, by means of the finite element method, steady-state thermal analyses of the coated and uncoated nozzles were compared, and the results show that the thermal barrier coating method dramatically reduced energy loss through the nozzle. It was found that the average heat flux was reduced by 89.4223% in the brass nozzle, 91.6678% in the copper nozzle, and 79.1361% in the hardened steel nozzle.
A Mathematical and Numerical Framework for Traffic-Induced Air Pollution Simulation in Bamako
Authors: Samaké Abdoulaye , Mahamane Amadou , Alassane Mahamadou , Diallo Ouaténi
Published: May 2022

We present a mathematical and numerical framework for the simulation of traffic-induced air pollution in Bamako. We consider a deterministic modeling approach where the spatio-temporal dynamics of the concentrations of air pollutants are governed by a so-called chemical transport model. The time integration and spatial discretization of the model are achieved using the forward Euler algorithm and the finite-element method, respectively. The traffic emissions are estimated using a road traffic simulation package called SUMO. The numerical results for two road traffic-induced air pollutants, namely the carbon monoxide (CO) and the fine particulate matter (PM2.5), support that the proposed framework is suited for reproducing the dynamics of the pollutants specified.
Elucidation of the Conformational Transition of Oligopeptidase B by an Integrative Approach Based on the Combination of X-ray, SAXS, and Essential Dynamics Sampling Simulation
Authors: Britikov Vladimir , Timofeev Vladimir , Petrenko Dmitry , Britikova Elena , Nikolaeva Alena , Vlaskina Anna , Boyko Konstantin , Mikhailova Anna , Rakitina Tatiana
Published: May 2022

Oligopeptidase B (OPB) is the least studied group from the prolyl oligopeptidase family. OPBs are found in bacteria and parasitic protozoa and represent pathogenesis factors of the corresponding infections. OPBs consist of two domains connected by a hinge region and have the characteristics of conformational dynamics, which include two types of movements: the bridging/separation of α/β-hydrolase catalytic and β-propeller-regulatory domains and the movement of a loop carrying catalytic histidine, which regulates an assembly/disassembly of the catalytic triad. In this work, an elucidation of the interdomain dynamics of OPB from Serratia proteamaculans (SpOPB) with and without modification of the hinge region was performed using a combination of X-ray diffraction analysis and small-angle X-ray scattering, which was complemented with an essential dynamics sampling (EDS) simulation. The first crystal structure of catalytically deficient SpOPB (SpOPBS532A) with an intact hinge sequence is reported. Similarly to SpOPB with modified hinges, SpOPBS532A was crystallized in the presence of spermine and adopted an intermediate conformation in the crystal lattice. Despite the similarity of the crystal structures, a difference in the catalytic triad residue arrangement was detected, which explained the inhibitory effect of the hinge modification. The SpOPBS532A structure reconstituted to the wild-type form was used as a starting point to the classical MD followed by EDS simulation, which allowed us to simulate the domain separation and the transition of the enzyme from the intermediate to open conformation. The obtained open state model was in good agreement with the experimental SAXS data.
Ni-CeO2/SBA-15 Catalyst Prepared by Glycine-Assisted Impregnation Method for Low-Temperature Dry Reforming of Methane
Authors: Yang Jiliang , Gong Dandan , Lu Xinkang , Han Cui , Liu Hui , Wang Luhui
Published: May 2022

Developing low-temperature nickel-based catalysts with good resistance to coking and sintering for dry reforming of methane (DRM) is of great significance. In this work, Ni (5 wt%) and CeO2 (5 wt%) were supported on SBA-15 porous material by glycine-assisted impregnation method to obtain Ni-CeO2/SBA-15-G catalyst. XRD and TEM results showed that the addition of glycine can effectively promote the dispersion of NiO and CeO2 in the pores of SBA-15. H2-TPR and XPS results confirmed the formation of stronger metal-support interaction. In addition, after the addition of glycine, the NixCe1−xOy solid solution content was increased significantly, meanwhile, the Ce3+ concentration was increased from 31% to 49%, accompanied by more oxygen vacancies and generation of active oxygen species. For the above reasons, Ni-CeO2/SBA-15-G had better catalytic performance in the low-temperature DRM test (20 h, 600 °C) with high GHSV (600,000 mL/gcat/h), its CH4 conversion after reaction of 20 h was 2 times that of Ni-CeO2/SBA-15-C catalyst prepared by a conventional impregnation method. TGA-DTA test also proved that Ni-CeO2/SBA-15-G almost completely eliminated carbon deposition. The above advantages of the Ni-CeO2/SBA-15-G catalyst may have originated from the complexation of glycine with metal cations and can prevent them from gathering.
Crystalline Derivatives of Dipyrazolo-1,5-diazocine and Dipyrazolopyrimidine: A Case of Unexpected Synthesis and Isostructural Polymorphism
Authors: Cuenú-Cabezas Fernando , Abonia Rodrigo , Gómez Castaño Jovanny A.
Published: May 2022

Pyrazole-phenylmethanimines (Shiff bases), Py–N=CH–Ph, form molecular crystals whose supramolecular and self-assembly properties can be tuned according to the substitution made on the aromatic and pyrazole rings. In pursuit of the first pyrazole-pyridinemethanimine member, Py–N=CH–Pyr, by following the well-known synthetic scheme for these Shiff bases, two hitherto unknown crystalline derivatives of dipyrazolo-1,5-diazocine and dipyrazolopyrimidine were obtained instead, this depending on the use or not of acetic acid as the catalyst. 1,5-diazocine crystallizes in a single P-1 triclinic packing system (Z = 2, Z′ = 1), while dipyrazolopyrimidine exhibits isostructural dimorphic behavior by adopting two (pale pink and yellow) alike P21/c monoclinic systems (both Z = 4, Z′ = 1) as a function of the solvent used. Crystal structures were resolved by means of X-ray diffraction technique and their intramolecular, intermolecular, and supramolecular assemblies analyzed with the assistance of decorated Hirshfeld surfaces and the topology study of electron density using the quantum-theory of atoms in molecules (QTAIM). Although both dipyrazolopyrimidine polymorphs are stabilized by the same type of noncovalent motifs, the pale pink crystal has a slightly more compact structure, with more efficient inter- and intramolecular interactions.
Biogeography and Diversification of the Tropical and Subtropical Asian Genus Gastrochilus (Orchidaceae, Aeridinae)
Authors: Li Yang , Jin Weitao , Zhang Liguo , Zhou Peng , Luo Yan , Zhu Ziwei , Xiang Xiaoguo
Published: May 2022

Tropical and subtropical Asia are major orchid diversity and endemism centers. However, the evolutionary dynamics of orchids in these areas remain poorly studied. Gastrochilus D. Don, a species-rich orchid genus from tropical and subtropical Asian forests, was employed to investigate the issue. We firstly used eight DNA regions to reconstruct the phylogeny and estimate the divergence times within Gastrochilus. We inferred the ancestral ranges and conducted a diversification analysis based on empirical and simulated data. Subsequently, we assessed the ancestral niche state and tested for phylogenetic signals in the evolution of niche conditions. Our results suggested that the most recent common ancestor of Gastrochilus occurred in the subtropical area of the East Asiatic region in the late Miocene (8.13 Ma). At least eight dispersal events and four vicariant events were inferred to explain the current distribution of Gastrochilus, associated with the global cooling from the Plio-Pleistocene. The genus experienced a slowly decreasing diversification rate since its origin, and no significant correlation between current niches and phylogenetic relatedness was observed. The diversification of Gastrochilus was attributed to accumulation through time, integrated with the intensification of the Asian Monsoon system during the Plio-Pleistocene, pollination, and epiphytism.