bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbe-associated molecular pattern recognition receptors have little effect on endophytic Arabidopsis thaliana microbiome assembly in the field
Authors: Oldstone-Jackson Caroline , Huang Feng , Bergelson Joy
Published: November 2023

Plant microbiome structure affects plant health and productivity. A limited subset of environmental microbes successfully establishes within plant tissues, but the forces underlying this selectivity remain poorly characterized. Transmembrane pattern recognition receptors (PRRs), used by plants to detect microbe-associated molecular patterns (MAMPs), are strong candidates for achieving this selectivity because PRRs can potentially interact with many members of the microbiome. Indeed, MAMPs found in many microbial taxa, including beneficials and commensals, can instigate a robust immune response that affects microbial growth. Surprisingly, we found that MAMP-detecting PRRs have little effect on endophytic bacterial and fungal microbiome structure in the field. We compared the microbiomes of four PRR knockout lines of Arabidopsis thaliana to wild-type plants in multiple tissue types over several developmental stages and detected only subtle shifts in fungal, but not bacterial, β-diversity in one of the four PRR mutants. In one developmental stage, lore mutants had slightly altered fungal β-diversity, indicating that LORE may be involved in plant-fungal interactions in addition to its known role in detecting certain bacterial lipids. No other effects of PRRs on α-diversity, microbiome variability, within-individual homogeneity, or microbial load were found. The general lack of effect suggests that individual MAMP-detecting PRRs are not critical in shaping the endophytic plant microbiome. Rather, we suggest that MAMP-detecting PRRs must either act in concert and/or are individually maintained through pleiotropic effects or interactions with coevolved mutualists or pathogens. Although unexpected, these results offer insights into the role of MAMP-detecting PRRs in plant-microbe interactions and help direct future efforts to uncover host genetic elements that control plant microbiome assembly.
Barriers to the development of community-based nursing in Iran
Authors: Peyrovi Hamid , Seyedfatemi Naiemeh , Goharinezhad Salime , Oghli Saeid Hossein
Published: November 2023

Purpose

Today, the care of chronic patients and older adult people in hospitals has moved towards community-based care, and health systems focus on disease prevention, health promotion, and rehabilitation. Community-based nurses play an essential role in early identification and intervention for these conditions. On the other hand, there is an increasing trend in ageing and chronic diseases in the world especially in Iran, which increases the importance of disease prevention and public health promotion. Therefore, the current research aims to identify barriers to the development of community-based nursing in Iran.

Methods

In this qualitative study, 12 semi-structured interviews were conducted with nursing experts recruited in the study by purposive sampling in 2021–2022. Interviews were recorded and transcribed and a framework analysis method was used to analyse the data.

Results

The results obtained from the analysis of documents and qualitative interviews led to the identification of 4 barriers: not having a specific position, inappropriate image of nursing in society, inadequacy of education with the needs of society, and high cost of home nursing services.

Conclusion

Improving the image of nursing in society, locating a special place in the health system, improving education, and adjusting the costs of home care could be the strategies that help the further development of community-based nursing (CBN).
Evolution of psychopathology, purpose in life, and moral courage in healthcare workers during the COVID-19 pandemic: a longitudinal study
Authors: Echeverria Iván , Roselló-Jiménez Lorena , Benito Ana , Rojas-Bernal Luz Angela , O’Higgins Marcelo , Haro Gonzalo
Published: November 2023

Introduction

Almost 2 years and five infection waves after the COVID-19 pandemic started, healthcare workers continued dealing with the pandemic situation and facing the health consequences and the mental health disorders it caused. This study aimed to evaluate the onset and progression of psychopathology as well as the role of predictor variables such as purpose in life and moral courage among healthcare workers during this time.

Materials and methods

This was a longitudinal prospective study carried out with 45 Spanish healthcare workers who answered two questionnaires, the first questionnaire in April–May 2020 (T1) and the second questionnaire in September–October 2021 (T2).

Results

Although 29.5% of the sample considered that their mental health had improved over this time, almost half of them (47.7%) said it had not changed, while 22.7% reported a decline in their mental health from the first time they were asked. Specifically, 46.8% presented anxiety, 23.4% depression, and 42.6% acute stress at T1, and 38.3% had anxiety, 17% depression, and 27.7% post-traumatic stress disorder at T2. Despite this, there were no differences between T1 and T2 anxiety scores (p = 0.53), although there was a decrease in depression (p = 0.03) and acute stress (p = 0.02) scores. Predictor variable outcomes such as purpose in life (p = 0.88) and moral courage (p = 0.86; p = 0.38) did not change over time, but when modelling the data, purpose in life predicted psychopathology at T1, which in turn affected the psychopathology results at T2.

Conclusion

This study showed that, although psychopathology decreased over the months, its prevalence remained high. Even though the purpose in life predicted psychopathology at T1, it seems that once the psychopathology is established (T2), the factors that would improve it would be different from the protective factors that prevented its establishment, which become secondary.
Study of the isomeric yield ratio in the photoneutron reaction of natural holmium induced by laser-accelerated electron beams
Authors: Zhang Jingli , Qi Wei , Fan Wenru , Cao Zongwei , Luo Kaijun , Tan Changxiang , Zhang Xiaohui , Deng Zhigang , Zhang Zhimeng , Li Xinxiang , Yuan Yun , Luo Wen , Zhou Weimin
Published: November 2023

Introduction: An accurate knowledge of the isomeric yield ratio (IR) induced by the photonuclear reaction is crucial to study the nuclear structure and reaction mechanisms. 165Ho is a good candidate for the investigation of the IR since the Ho target has a natural abundance of 100% and the residual nuclide has a good decay property.

Methods: In this study, the photoneutron production of 164m, gHo induced by laser-accelerated electron beams is investigated experimentally. The γ-ray spectra of activated Ho foils are off-line detected. Since the direct transitions from the 164mHo are not successfully observed, we propose to extract the IRs of the 164m, gHo using only the photopeak counts from the ground-state decay.

Results: The production yields of 164m, gHo are extracted to be (0.45 ± 0.10) × 106 and (1.48 ± 0.14) × 106 per laser shot, respectively. The resulting IR is obtained to be 0.30 ± 0.08 at the effective γ-ray energy of 12.65 MeV.

Discussion: The present data, available experimental data, and TALYS calculations are then compared to examine the role of the excitation energy. It is found that besides the giant dipole resonance, the excitation energy effect also plays a key role in the determination of the IRs.
Renal Lobulation—A Benign Macroanatomical Variation?
Authors: Covantsev Serghei , Arnaut Oleg , Mulaeva Karina , Belic Olga
Published: November 2023

Introduction: Renal lobulation (also known as fetal or embryonic lobulation) is a rare variation during development in which renal lobules have a visible anatomical space between them, and this can be seen in 0.5–4% of adults. Material and methods: this study was conducted on 54 human kidneys from patients who died due to causes unrelated to renal pathology which were fixed in a 10% formaldehyde solution and then carefully dissected. Results: The group with fetal lobulation (n = 16) was associated with a length M = 9.89 (SD = 0.6, p = 0.15). By comparison, the kidneys without lobulation (n = 38) were associated with a numerically longer length M = 10.29 (SD = 0.607, p = 0.098). To test the hypothesis that lobulation is associated with a statistically significant different length a Mann–Whitney test was performed, which indicated that the length of the kidneys is smaller in scase of lobulation U = 198, Z = −2.04, p = 0.04. Cross-tabulation also demonstrated that kidney lobulation may be influenced by the presence of polar arteries with r = 0.41 (p < 0.02). The likelihood ratio was 7.28, df 1, p = 0.003, with an odds ratio of 6.857 (CI 95% = 1.84–25.61). Logistic regression analysis demonstrated that kidneys with lobulation were 6.85 times more likely to have polar arteries than kidneys without lobulation. Conclusions: the data from our research indicate that even though no pathological conditions have been linked with lobulated kidneys, the incidence of vascular variations (specifically polar arteries) is higher when there is persistent fetal lobulation.
Pheromone Sensing in Mammals: A Review of the Vomeronasal System
Authors: Torres Mateo V. , Ortiz-Leal Irene , Sanchez-Quinteiro Pablo
Published: November 2023

This review addresses the role of chemical communication in mammals, giving special attention to the vomeronasal system in pheromone-mediated interactions. The vomeronasal system influences many social and sexual behaviors, from reproduction to species recognition. Interestingly, this system shows greater evolutionary variability compared to the olfactory system, emphasizing its complex nature and the need for thorough research. The discussion starts with foundational concepts of chemocommunication, progressing to a detailed exploration of olfactory systems. The neuroanatomy of the vomeronasal system stands in contrast with that of the olfactory system. Further, the sensory part of the vomeronasal system, known as the vomeronasal organ, and the integration center of this information, called the accessory olfactory bulb, receive comprehensive coverage. Secondary projections of both the olfactory and vomeronasal systems receive attention, especially in relation to the dual olfactory hypothesis. The review concludes by examining the organization of the vomeronasal system in four distinct mammalian groups: rodents, marsupials, herpestids, and bovids. The aim is to highlight the unique morphofunctional differences resulting from the adaptive changes each group experienced.
The Role of Ozone as an Nrf2-Keap1-ARE Activator in the Anti-Microbial Activity and Immunity Modulation of Infected Wounds
Authors: Franzini Marianno , Valdenassi Luigi , Pandolfi Sergio , Tirelli Umberto , Ricevuti Giovanni , Chirumbolo Salvatore
Published: November 2023

Ozone is an allotrope of oxygen, widely known to exert an anti-oxidant potential. The ability of low, controlled and standardized doses of ozone in the ozone adjunct treatment of bacterial infections, which occur in wounds, is engaging clinical research to deepen the role of ozone in eradicating even multidrug-resistant bacteria. Ozone activates the nuclear factor erythroid 2-related factor 2 (Nrf2), and this activation triggers a complex cascade of events, which ultimately leads to macrophage training and an improvement in their ability to operate a clearance of bacteria in the patient’s anatomical districts. In this review, we try to elucidate the recent evidence about the mechanisms with which ozone can actually remove bacteria and even multi-drug-resistant (MDR) bacteria, accounting on its complex ability in modulating immunity.
Multistep Approach Points to Compounds Responsible for the Biological Activity and Safety of Hydrolates from Nine Lamiaceae Medicinal Plants on Human Skin Fibroblasts
Authors: Smiljanić Katarina , Prodić Ivana , Trifunovic Sara , Krstić Ristivojević Maja , Aćimović Milica , Stanković Jeremić Jovana , Lončar Biljana , Tešević Vele
Published: November 2023

As byproducts of essential oil distillation, hydrolates are used in natural cosmetics/biomedicine due to their beneficial skin effects. However, data on their safety with relevant biological targets, such as human skin cells, are scarce. Therefore, we have tested nine hydrolates from the Lamiaceae family with skin fibroblasts that are responsible for extracellular collagenous matrix builds. Thyme, oregano, and winter savoury hydrolates showed several times higher total phenolics, which correlated strongly with their radical scavenging and antioxidative capacity; there was no correlation between their viability profiles and the reducing sugar levels. No proteins/peptides were detected. All hydrolates appeared safe for prolonged skin exposure except for 10-fold diluted lavender, which showed cytotoxicity (~20%), as well as rosemary and lavandin (~10%) using viability, DNA synthesis, and cell count testing. Clary sage, oregano, lemon balm, and thyme hydrolates (10-fold diluted) increased fibroblast viability and/or proliferation by 10–30% compared with the control, while their viability remained unaffected by Mentha and winter savoury. In line with the STITCH database, increased viability could be attributed to thymol presence in oregano and thyme hydrolates in lemon balm, which is most likely attributable to neral and geranial. The proliferative effect of clary sage could be supported by alpha-terpineol, not linalool. The major volatile organic compounds (VOCs) associated with cytotoxic effects on fibroblasts were borneol, 1,8-cineole, and terpinene-4-ol. Further research with pure compounds is warranted to confirm the roles of VOCs in the observed effects that are relevant to cosmetic and wound healing aspects.
In Silico Design of a New Epitope-Based Vaccine against Grass Group 1 Allergens
Authors: Moten Dzhemal , Batsalova Tsvetelina , Apostolova Desislava , Mladenova Tsvetelina , Dzhambazov Balik , Teneva Ivanka
Published: November 2023

Allergic diseases are a global public health problem that affects up to 30% of the population in industrialized societies. More than 40% of allergic patients suffer from grass pollen allergy. Grass pollen allergens of group 1 and group 5 are the major allergens, since they induce allergic reactions in patients at high rates. In this study, we used immunoinformatic approaches to design an effective epitope-based vaccine against the grass group 1 allergens. After the alignment of all known pollen T-cell and B-cell epitopes from pollen allergens available in the public databases, the epitope GTKSEVEDVIPEGWKADTSY was identified as the most suitable for further analyses. The target sequence was subjected to immunoinformatics analyses to predict antigenic T-cell and B-cell epitopes. Population coverage analysis was performed for CD8+ and CD4+ T-cell epitopes. The selected T-cell epitopes (VEDVIPEGW and TKSEVEDVIPEGWKA) covered 78.87% and 98.20% of the global population and 84.57% and 99.86% of the population of Europe. Selected CD8+, CD4+ T-cell and B-cell epitopes have been validated by molecular docking analysis. CD8+ and CD4+ T-cell epitopes showed a very strong binding affinity to major histocompatibility complex (MHC) class I (MHC I) molecules and MHC class II (MHC II) molecules with global energy scores of −72.1 kcal/mol and −89.59 kcal/mol, respectively. The human IgE-Fc (PDB ID 4J4P) showed a lower affinity with B-cell epitope (ΔG = −34.4 kcal/mol), while the Phl p 2-specific human IgE Fab (PDB ID 2VXQ) had the lowest binding with the B-cell epitope (ΔG = −29.9 kcal/mol). Our immunoinformatics results demonstrated that the peptide GTKSEVEDVIPEGWKADTSY could stimulate the immune system and we performed ex vivo tests showed that the investigated epitope activates T cells isolated from patients with grass pollen allergy, but it is not recognized by IgE antibodies specific for grass pollen allergens. This confirms the importance of such studies to establish universal epitopes to serve as a basis for developing an effective vaccine against a particular group of allergens. Further in vivo studies are needed to validate the effectiveness of such a vaccine against grass pollen allergens.
Architecture of Medieval Armenia as a Field of Research for Russian and Italian Scholars: Comparative Analyses of the Historiography
Authors: Kazaryan Armen
Published: November 2023

For the first time in the literature, this study provides an analysis of the activities of two major architectural–archeological missions that investigated the architectural heritage of the Armenian Highlands: the Russian Ani Archaeological Expedition (1892–1893 and 1904–1917) and the Italian academic programs of the Universities of Rome and Venice and that of Milan Polytechnic (from 1966 to the 1980s). In this article, the results of the conducted research are compared, and their contribution to the development of the history of medieval architecture is evaluated. The differences in the results are related to the chronological distance between the missions, as well as the main focus of each work: the activities of the Russians are primarily archeological, while those of the Italian groups are architectural. The head of the Ani Institute, Nikolay Marr, set himself the task of exhibiting the original artifacts in the museum he had created in the medieval capital of Armenia, Ani, while the Italian professors relied on photography for both permanent and touring exhibitions. The second mission was in unspoken contact with the first, forming a kind of time-stretched dialog. Although, by the 1970s, almost none of the participants in Marr’s expedition remained alive, his scientific works were periodically being published, with some still waiting their turn in the scientific archives.
The Relationship between PM2.5 and Health Vulnerability in Argentina in 2010
Authors: Bullo Manuela , Lakkis Gabriela , Pustilnik Martin , Bonfiglio Juan Ignacio , Di Pasquale Ricardo , Gonzalez Luciana Marisol , Gonzalez-Aleman Gabriela , Lamas Maria Cristina , Salvia Agustin , Langsam Martín , Olego Tomás , Starosta Valentín , Perez-Lloret Santiago
Published: November 2023

This study aimed to further explore the concept of health vulnerability in Argentina, including environmental pollution in 2010. To this end, we developed a geo-referenced database of PM2.5 concentrations and emissions data from the national emissions inventory to analyze possible correlations with the demographic, activity, education, and health data from the 2010 national census. In addition, to provide a more complete picture of health vulnerability in Argentina, an extended index (SVI + PM2.5) was constructed and mapped, including PM concentration. We obtained data for annual PM2.5 values emissions and air concentrations in Argentina from public sources (GEEA-AEIv3.0M for emissions and the Atmospheric Composition Analysis Group V5.GL.03 dataset for surface PM2.5). We evaluated health vulnerability using the “Sanitary Vulnerability Index” (SVI). PM2.5 emissions are concentrated in urban and intensive agricultural areas of Argentina. PM2.5 air concentrations were acceptable (≤10 µg/m3) in only 15% of the Argentinean territory. The newly developed SVI + PM2.5 index showed that exposure to particulate material significantly increases the vulnerability shown by SVI in almost all census blocks. These results indicate that the new SVI + PM2.5 index might help identify populations that are at risk because of social issues or air pollution.
Role of Akt/Protein Kinase B in Cancer Metastasis
Authors: Islam Mohammad , Jones Sarah , Ellis Ian
Published: November 2023

Metastasis is a critical step in the process of carcinogenesis and a vast majority of cancer-related mortalities result from metastatic disease that is resistant to current therapies. Cell migration and invasion are the first steps of the metastasis process, which mainly occurs by two important biological mechanisms, i.e., cytoskeletal remodelling and epithelial to mesenchymal transition (EMT). Akt (also known as protein kinase B) is a central signalling molecule of the PI3K-Akt signalling pathway. Aberrant activation of this pathway has been identified in a wide range of cancers. Several studies have revealed that Akt actively engages with the migratory process in motile cells, including metastatic cancer cells. The downstream signalling mechanism of Akt in cell migration depends upon the tumour type, sites, and intracellular localisation of activated Akt. In this review, we focus on the role of Akt in the regulation of two events that control cell migration and invasion in various cancers including head and neck squamous cell carcinoma (HNSCC) and the status of PI3K-Akt pathway inhibitors in clinical trials in metastatic cancers.
Relationship between the Ubiquitin–Proteasome System and Autophagy in Colorectal Cancer Tissue
Authors: Bednarczyk Martyna , Muc-Wierzgoń Małgorzata , Dzięgielewska-Gęsiak Sylwia , Waniczek Dariusz
Published: November 2023

Background: Dysregulation of the autophagy process via ubiquitin is associated with the occurrence of a number of diseases, including cancer. The present study analyzed the changes in the transcriptional activity of autophagy-related genes and the ubiquitination process (UPS) in colorectal cancer tissue. (2) Methods: The process of measuring the transcriptional activity of autophagy-related genes was analyzed by comparing colorectal cancer samples from four clinical stages I-IV (CS I-IV) of adenocarcinoma to the control (C). The transcriptional activity of genes associated with the UPS pathway was determined via the microarray technique (HG-U133A, Affymetrix). (3) Results: Of the selected genes, only PTEN-induced kinase 1 (PINK1) indicated statistical significance for all groups of colon cancer tissue transcriptome compared to the control. The transcriptional activity of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene increased in all stages of the cancer, but the p-value was only less than 0.05 in CSIV vs. C. Forkhead box O1 (FOXO 1) and ubiquitin B (UBB) are statistically overexpressed in CSI. (4) Conclusions: The pathological expression changes in the studied proteins observed especially in the early stages of colorectal cancer suggest that the dysregulation of ubiquitination and autophagy processes occur during early neoplastic transformation. Stopping or slowing down the processes of removal of damaged proteins and their accumulation may contribute to tumor progression and poor prognosis.
The Clinical Relevance of Selected Cytokines in Newly Diagnosed Multiple Myeloma Patients
Authors: Mielnik Michał , Szudy-Szczyrek Aneta , Homa-Mlak Iwona , Mlak Radosław , Podgajna-Mielnik Martyna , Gorący Aneta , Małecka-Massalska Teresa , Hus Marek
Published: November 2023

Multiple myeloma (MM) is the second most common hematological neoplasm. Cytokines, chemokines, and their receptors, induced by the microenvironment of MM, participate in tumor growth, the attraction of leukocytes, cell homing, and bone destruction. This study aimed to assess the correlation between the pretreatment serum concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), angiogenic chemokine monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) and the clinical outcomes and survival of patients newly diagnosed with MM. The study group consisted of 82 individuals. The IL-8 concentration was significantly positively correlated with the age of onset (p = 0.007), the International Staging System (ISS) stage (p = 0.03), the Eastern Cooperative Oncology Group (ECOG) performance status (p < 0.001), the degree of anemia before treatment (p < 0.0001), the degree of kidney disease (p < 0.001), and VEGF (p = 0.0364). Chemotherapy responders had significantly lower concentrations of IL-8 (p < 0.001), IL-6 (p < 0.001), and VEGF (p = 0.04) compared with non-responders. Patients with treatment-induced polyneuropathy had significantly higher levels of IL-8 (p = 0.033). Patients with a high level of IL-6 had a 2-fold higher risk of progression-free survival (PFS) reduction (17 vs. 35 months; HR = 1.89; p = 0.0078), and a more than 2.5-fold higher risk of overall survival (OS) reduction (28 vs. 78 months; HR = 2.62; p < 0.001). High levels of IL-6, IL-8, and VEGF demonstrated significant predictive values for some clinical conditions or outcomes of newly diagnosed MM patients. Patients with an early response to chemotherapy had a significantly lower concentration of these cytokines. A high pretreatment IL-6 concentration was an independent negative prognostic marker for newly diagnosed MM patients.
Light-Stimulated IGZO Transistors with Tunable Synaptic Plasticity Based on Casein Electrolyte Electric Double Layer for Neuromorphic Systems
Authors: Kim Hwi-Su , Park Hamin , Cho Won-Ju
Published: November 2023

In this study, optoelectronic synaptic transistors based on indium–gallium–zinc oxide (IGZO) with a casein electrolyte-based electric double layer (EDL) were examined. The casein electrolyte played a crucial role in modulating synaptic plasticity through an internal proton-induced EDL effect. Thus, important synaptic behaviors, such as excitatory post-synaptic current, paired-pulse facilitation, and spike rate-dependent and spike number-dependent plasticity, were successfully implemented by utilizing the persistent photoconductivity effect of the IGZO channel stimulated by light. The synergy between the light stimulation and the EDL effect allowed the effective modulation of synaptic plasticity, enabling the control of memory levels, including the conversion of short-term memory to long-term memory. Furthermore, a Modified National Institute of Standards and Technology digit recognition simulation was performed using a three-layer artificial neural network model, achieving a high recognition rate of 90.5%. These results demonstrated a high application potential of the proposed optoelectronic synaptic transistors in neuromorphic visual systems.
Creation of a 3D Goethite–Spongin Composite Using an Extreme Biomimetics Approach
Authors: Kubiak Anita , Voronkina Alona , Pajewska-Szmyt Martyna , Kotula Martyna , Leśniewski Bartosz , Ereskovsky Alexander , Heimler Korbinian , Rogoll Anika , Vogt Carla , Rahimi Parvaneh , Falahi Sedigheh , Galli Roberta , Langer Enrico , Förste Maik , Charitos Alexandros , Joseph Yvonne , Ehrlich Hermann , Jesionowski Teofil
Published: November 2023

The structural biopolymer spongin in the form of a 3D scaffold resembles in shape and size numerous species of industrially useful marine keratosan demosponges. Due to the large-scale aquaculture of these sponges worldwide, it represents a unique renewable source of biological material, which has already been successfully applied in biomedicine and bioinspired materials science. In the present study, spongin from the demosponge Hippospongia communis was used as a microporous template for the development of a new 3D composite containing goethite [α-FeO(OH)]. For this purpose, an extreme biomimetic technique using iron powder, crystalline iodine, and fibrous spongin was applied under laboratory conditions for the first time. The product was characterized using SEM and digital light microscopy, infrared and Raman spectroscopy, XRD, thermogravimetry (TG/DTG), and confocal micro X-ray fluorescence spectroscopy (CMXRF). A potential application of the obtained goethite–spongin composite in the electrochemical sensing of dopamine (DA) in human urine samples was investigated, with satisfactory recoveries (96% to 116%) being obtained.
A New Case of Autosomal-Dominant POLR3B-Related Disorder: Widening Genotypic and Phenotypic Spectrum
Authors: Colona Vito Luigi , Bertini Enrico , Digilio Maria Cristina , D’Amico Adele , Novelli Antonio , Pro Stefano , Pisaneschi Elisa , Nicita Francesco
Published: November 2023

POLR3B encodes the RPC2 subunit of RNA polymerase III. Pathogenic variants are associated with biallelic hypomyelinating leukodystrophy belonging to the POLR-related disorders. Recently, the association with dominant demyelinating neuropathy, classified as Charcot–Marie–Tooth syndrome type 1I (CMT1I), has been reported as well. Here we report on an additional patient presenting with developmental delay and generalized epilepsy, followed by the onset of mild pyramidal and cerebellar signs, vertical gaze palsy and subclinical demyelinating polyneuropathy. A new heterozygous de novo missense variant, c.1297C > G, p.Arg433Gly, in POLR3B was disclosed via trio-exome sequencing. In silico analysis confirms the hypothesis on the variant pathogenicity. Our research broadens both the genotypic and phenotypic spectrum of the autosomal-dominant POLR3B-related condition.
Structural and Physiological Modeling (SAPM) for the Analysis of Functional MRI Data Applied to a Study of Human Nociceptive Processing
Authors: Stroman Patrick W. , Umraw Maya , Keast Brieana , Algitami Hannan , Hassanpour Shima , Merletti Jessica
Published: November 2023

A novel method has been developed for analyzing connectivity between regions based on functional magnetic resonance imaging (fMRI) data. This method, termed structural and physiological modeling (SAPM), combines information about blood oxygenation-level dependent (BOLD) responses, anatomy, and physiology to model coordinated signaling across networks of regions, including input and output signaling from each region and whether signaling is predominantly inhibitory or excitatory. The present study builds on a prior proof-of-concept demonstration of the SAPM method by providing evidence for the choice of network model and anatomical sub-regions, demonstrating the reproducibility of the results and identifying statistical thresholds needed to infer significance. The method is further validated by applying it to investigate human nociceptive processing in the brainstem and spinal cord and comparing the results to the known neuroanatomy, including anatomical regions and inhibitory and excitatory signaling. The results of this analysis demonstrate that it is possible to obtain reliable information about input and output signaling from anatomical regions and to identify whether this signaling has predominantly inhibitory or excitatory effects. SAPM provides much more detailed information about neuroanatomy than was previously possible based on fMRI data.
Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging-Tractography in Resective Brain Surgery: Lesion Coverage Strategies and Patient Outcomes
Authors: Kokkinos Vasileios , Chatzisotiriou Athanasios , Seimenis Ioannis
Published: November 2023

Diffusion tensor imaging (DTI)-tractography and functional magnetic resonance imaging (fMRI) have dynamically entered the presurgical evaluation context of brain surgery during the past decades, providing novel perspectives in surgical planning and lesion access approaches. However, their application in the presurgical setting requires significant time and effort and increased costs, thereby raising questions regarding efficiency and best use. In this work, we set out to evaluate DTI-tractography and combined fMRI/DTI-tractography during intra-operative neuronavigation in resective brain surgery using lesion-related preoperative neurological deficit (PND) outcomes as metrics. We retrospectively reviewed medical records of 252 consecutive patients admitted for brain surgery. Standard anatomical neuroimaging protocols were performed in 127 patients, 69 patients had additional DTI-tractography, and 56 had combined DTI-tractography/fMRI. fMRI procedures involved language, motor, somatic sensory, sensorimotor and visual mapping. DTI-tractography involved fiber tracking of the motor, sensory, language and visual pathways. At 1 month postoperatively, DTI-tractography patients were more likely to present either improvement or preservation of PNDs (p = 0.004 and p = 0.007, respectively). At 6 months, combined DTI-tractography/fMRI patients were more likely to experience complete PND resolution (p < 0.001). Low-grade lesion patients (N = 102) with combined DTI-tractography/fMRI were more likely to experience complete resolution of PNDs at 1 and 6 months (p = 0.001 and p < 0.001, respectively). High-grade lesion patients (N = 140) with combined DTI-tractography/fMRI were more likely to have PNDs resolved at 6 months (p = 0.005). Patients with motor symptoms (N = 80) were more likely to experience complete remission of PNDs at 6 months with DTI-tractography or combined DTI-tractography/fMRI (p = 0.008 and p = 0.004, respectively), without significant difference between the two imaging protocols (p = 1). Patients with sensory symptoms (N = 44) were more likely to experience complete PND remission at 6 months with combined DTI-tractography/fMRI (p = 0.004). The intraoperative neuroimaging modality did not have a significant effect in patients with preoperative seizures (N = 47). Lack of PND worsening was observed at 6 month follow-up in patients with combined DTI-tractography/fMRI. Our results strongly support the combined use of DTI-tractography and fMRI in patients undergoing resective brain surgery for improving their postoperative clinical profile.
The Spatiotemporal Distribution Characteristics and Driving Factors of Carbon Emissions in the Chinese Construction Industry
Authors: Yang Jun , Zheng Xiaodan
Published: November 2023

As a pillar industry of the national economy, the construction industry not only promotes urban development and social prosperity but also has an irreversible impact on the environment with the trend of high carbon emissions. Therefore, it is of great significance for the construction industry to take the lead in achieving carbon emissions reduction. This paper attempts to explore the spatiotemporal distribution characteristics and specific driving factors of carbon emissions in the construction industry in 30 provinces of China from 2011 to 2020 based on the spatial econometric analysis, so as to clarify the development trajectory and formation mechanism. The key findings are (1) there are obvious differences in carbon emissions across Chinese provinces, culminating in a distinct “Belt–Ring–Dot” spatial distribution; (2) the carbon emissions in the construction industry follow an inverted U-shaped pattern from south to north, with lower emissions in the west and higher emissions in the east, which means the pressure and potential of carbon emissions reduction coexist; (3) the Moran’s I index values from 2011 to 2020 were all greater than 0, with a maximum value of 0.284, indicating that there is a notable positive spatial correlation in carbon emissions in the construction industry between provinces; and (4) among the five factors, the number of employees displays the most pronounced spatial correlation, passing the test a total of eight times, and the mean test coefficient is the largest at 0.552. This factor positively influences carbon emissions alongside the gross product. On the other hand, the patents granted factor significantly inhibits carbon emissions with all test coefficients being negative with a maximum absolute value of 0.166. The impact of the technical equipment rate shows a characteristic of initial positive stimulation followed by later negative inhibition. In contrast, the urbanization rate exhibits the weakest spatial correlation with the minimum test coefficient being only 0.001.
Winner-Take-All and Loser-Take-All Circuits: Architectures, Applications and Analytical Comparison
Authors: Rahiminejad Ehsan , Aminzadeh Hamed
Published: November 2023

Different winner-take-all (WTA) and loser-take-all (LTA) circuits are studied, and their operations are analyzed in this review. The exclusive operation of the current conveyor, binary tree, and time-domain WTA/LTA architectures, as the most important architectures reported in the literature, are compared from the perspectives of power consumption, speed, and precision.
Fenbendazole Exhibits Differential Anticancer Effects In Vitro and In Vivo in Models of Mouse Lymphoma
Authors: Jung Haebeen , Kim Si-Yeon , Joo Hong-Gu
Published: November 2023

Fenbendazole (FBZ) has been safely used as an antiparasitic agent in animals for decades, and the anticancer effects of FBZ have been studied through various mechanisms. However, there is a lack of in vivo studies that include lymphoma. Therefore, this study examined the effects of FBZ on EL-4 cells and a mouse T lymphoma model. FBZ induced G2/M phase arrest in EL-4 cells, resulting in cell death and decreased metabolic activity. However, FBZ had no anticancer effects on an EL-4 mouse lymphoma model in vivo, as evident by rapid weight loss and tumor growth comparable to the control. The FBZ-treated EL-4 cells expressed higher levels of PD-L1 and CD86, which are associated with T cell immunity in the tumor microenvironment (TME), than the controls. Furthermore, the hematoxylin and eosin staining of the FBZ-treated tumor tissues showed a starry sky pattern, which is seen in actively proliferating cancer tissues, and an immunohistochemical analysis revealed a high percentage of immunosuppressive M2 macrophages. These changes in the immune activity in the TME contradict the results of the in vitro experiments, and further studies are needed to determine the detailed mechanisms by which FBZ induces these responses.
Facile Synthesis of PVP-Coated Silver Nanoparticles and Evaluation of Their Physicochemical, Antimicrobial and Toxic Activity
Authors: Neto Francisco N. Souza , Morais Leonardo A. , Gorup Luiz F. , Ribeiro Lucas S. , Martins Tassia J. , Hosida Thayse Y. , Francatto Patricia , Barbosa Debora B. , Camargo Emerson R. , Delbem Alberto C. B.
Published: November 2023

This study focuses on the synthesis of silver nanoparticles (AgNPs) at different high concentrations and investigates their physicochemical properties, antimicrobial activity, and cytotoxicity. AgNPs were synthesized using the alcohol reduction process, involving the reduction of AgNO3 and its subsequent stabilization via PVP at 80 °C for 4 h. The AgNO3/PVP molar ratio and the average molecular weight were modified in this study. Characterization analyses revealed that the synthesized AgNPs exhibited characteristic surface plasmon resonance absorption peaks at approximately 415 nm, as observed in the UV–Vis spectrum. The results presented in X-ray diffractograms confirmed the face-centered cubic structure of metallic Ag in the nanoparticles. The nanoparticles demonstrated uniform size and shape, with controllable dimensions ranging from 3 to 800 nm. Regarding antimicrobial activity, the MIC solutions exhibited higher potency against the planktonic cells of Candida albicans. The determination of inhibition halos indicated that the silver nanoparticles had an impact on the microorganisms Streptococcus mutans, Candida albicans, and Actinomyces israelii. Furthermore, lower-concentration compositions showed reduced cytotoxic effects compared to higher-concentration particles. Based on the findings, it was concluded that the AgNO3/PVP molar ratio plays a crucial role in the production of AgNPs. These synthesized nanoparticles exhibit desirable physicochemical properties and demonstrate potential antimicrobial activity and controlled cytotoxicity.
Iron Surveillance and Management in Gastro-Intestinal Oncology Patients: A National Physician Survey
Authors: Richard Emilie S. , Hrycyshyn Adriyan , Salman Noor , Remtulla Tharani Alliya , Abbruzzino Alexandria , Smith Janet , Kachura Jacob J. , Sholzberg Michelle , Mosko Jeffrey D. , Chadi Sami A. , Burkes Ronald L. , Pankiw Maya , Brezden-Masley Christine
Published: November 2023

Purpose: Iron deficiency (ID) is a complication of gastrointestinal (GI) cancers that may manifest as iron deficiency anemia (IDA). Serum ferritin monitoring and oral iron supplementation have the limitations of being falsely elevated and poorly absorbed, respectively. This study aims to assess the discordance in surveillance, treatment practices, and awareness of ID/IDA in GI cancer patients by Canadian physicians treating these patients. Methods: From February 2020 to September 2021, a 22-question electronic survey was sent to medical oncologists (MOs), surgical oncologists (SOs), and gastroenterologists (GEs). The survey collected information about four domains: physician demographics, surveillance practices, treatment practices, and awareness of ID/IDA in GI cancer patients and ASCO/ASH guidelines. Results: A total of 108 (34 MOs, 19 SOs, and 55 GEs) of the 872 (12.4%) invited physicians completed the survey. Of these, 26.5% of MOs, 36.8% of SOs, and 70.9% of GEs measured baseline iron parameters, with few continuing surveillance throughout treatment. Ferritin was widely measured by MOs (88.9%), SOs (100%), and GEs (91.4%). Iron was supplemented if ID/IDA was identified pre-treatment by 66.7% of MOs, 85.7% of SOs, and 94.2% of GEs. Parenteral iron was prescribed by SOs (100%), while oral iron was prescribed by MOs (83.3%) and GEs (87.9%). Only 18.6% of physicians were aware of the ASCO/ASH guidelines regarding erythropoiesis-stimulating agents with parenteral iron for treating chemotherapy-induced anemia. Conclusion: Results illustrate variations in practice patterns for IDA management across the different physician specialties. Moreover, there appeared to be gaps in the knowledge and care surrounding evidence-based IDA management principles which may contribute to poor clinical outcomes.
The Greater Midlands—A Mid-Elevation Centre of Floristic Endemism in Summer-Rainfall Eastern South Africa
Authors: Carbutt Clinton
Published: November 2023

The Midlands region of KwaZulu-Natal (KZN) Province in South Africa was hitherto a putative centre of floristic endemism (CFE) based on conjecture. The aim of this study was to empirically explore this concept by delineating unambiguous boundaries for this CFE and documenting the endemic spermatophytes within a conservation framework. The Greater Midlands Centre of Floristic Endemism (GMCFE), a more expanded study area than the parochial Midlands region of KZN, is formally described as southern Africa’s 20th CFE. It is a mid-elevation region occupying the greater Midlands of KZN, with extensions of contiguous grasslands extending northwards into southern Mpumalanga and southwards into north-eastern Eastern Cape. This “foothills” CFE covers ca. 77,000 km2 of predominantly mesic C4 grassland, ranging in elevation from ca. 700–2200 m a.s.l. It is congruent with the “sub-escarpment ecoregion,” essentially a composite of the Sub-escarpment Grassland and Savanna Bioregions and the sub-escarpment grasslands of southern Mpumalanga and northern KZN. The GMCFE hosts at least 220 endemic spermatophytes, of which almost a fifth belong to the family Apocynaceae. Families Asteraceae, Asphodelaceae, Fabaceae, and Iridaceae also contribute significantly. Genera Ceropegia, Aloe, Dierama, Kniphofia, Helichrysum, and Streptocarpus contribute the most endemics. More than half are forbs, and almost three-quarters are confined to the Grassland Biome. Endemic radiations are attributed to geodiversity and geological complexity (especially the strong lithological influence of dolerite); physiographic heterogeneity (particularly elevation gradients and variable terrain units); strategic proximity to hyper-diverse temperate and subtropical “border floras”; and localized pollinator-driven adaptive radiations. Of alarming concern is the high number of threatened plant taxa, with ca. 60% of the endemic flora Red Listed in threat categories (CE, E, and VU) or considered “rare”. Extremely low levels of formal protection and poor ecological connectivity, coupled with high levels of land transformation and intensive utilization, render the GMCFE one of the most imperilled CFE in South Africa. Urgent conservation action is required to safeguard this unique and highly threatened “rangeland flora” and stem the biodiversity crisis gripping the region.
Metabolic Effects of Anti-TNF-α Treatment in Rheumatoid Arthritis
Authors: Macáková Kristína , Tekeľová Mária , Mlynáriková Vanda , Šebeková Katarína , Vlková Barbora , Celec Peter , Šteňová Emöke
Published: November 2023

Rheumatoid arthritis (RA) is associated with high cardiovascular mortality. It is not clear whether the metabolic consequences of chronic inflammation are involved. Biological disease-modifying anti-rheumatic drugs (bDMARDs) are highly efficient in the treatment of inflammation in RA. In this study, we aimed to describe the metabolic effects of anti-TNF-α treatment in RA patients. The clinical status of 16 patients was assessed using disease activity score-28 (DAS28) and C-reactive protein (CRP). Plasma samples were collected before treatment with anti-TNF-α treatment as well as after three and six months of treatment. Markers of lipid and glucose metabolism, as well as renal biomarkers, were assessed using standard biochemistry. ELISA was used for the quantification of insulin, leptin, and adiponectin. Although fasting insulin decreased by 14% at the end of the study, most of the analyzed parameters did not show any statistically or clinically significant dynamics. The exception was total bilirubin and cholesterol, which increased by 53% and 14%, respectively, after six months of treatment with anti-TNF-α treatment. Anti-TNF-α treatment did not induce major metabolic changes despite the strong anti-inflammatory and clinical symptoms of RA. Further studies will show whether longer observations are required for the detection of the metabolic effects of the anti-inflammatory treatment. Additional research is needed to understand the observed effect of bilirubin as an important endogenous antioxidant.
Prognostic Significance of Histopathological Parameters for Salivary Gland Adenoid Cystic Carcinoma
Authors: de Morais Everton Freitas , de Farias Morais Hannah Gil , de Almeida Freitas Roseana , Coletta Ricardo D.
Published: November 2023

Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor that accounts for approximately 1% of all head and neck cancers. Despite its initial indolent behavior, long-term survival is poor due to locoregional recurrence in approximately 40% and distant metastasis in up to 60% of patients who undergo radical treatment. The histological parameters of ACC and the combination of these parameters in histopathological grading systems provide valuable prognostic information about the clinical course of the disease. Within this context, this review aims to analyze the impact of histopathological parameters, individual or combined in histopathological grading systems of malignancy, on ACC prognosis. Individual histopathological parameters such as solid pattern, presence of tumor necrosis, high-grade transformation, dominance of the epithelial component, presence of perineural and lymphovascular invasion, and positive surgical margins have negative impacts on the survival of patients with ACC. There are currently four histopathological grading systems for ACC; however, few studies have validated these systems and most of them explored small cohorts with short follow-up. Considering that the application of grading systems has been associated with ACC prognosis, a broader validation will allow not only their use for prognostic prediction but also assist in treatment planning.