bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Canopy Damage and Litterfall Input on CO2-Fixing Bacterial Communities
Authors: Yu Fei , Li Zhen , Liang Junfeng , Zhao Houben
Published: August 2023

Extreme weather events often cause canopy disturbance and litter deposition. To study the CO2-fixing bacterial response to forest damage, we simulated the canopy damage caused by extreme weather with four different treatments: control (CN), canopy trimming + removal of branches and leaves debris (TR), canopy trimming + retaining of branches and leaves debris (TD), and undamaged + transplantation of branches and leaves debris (UD). We used the cbbL gene, which encodes ribulose-1,5-biphosphate carboxylase/oxygenase (RubisCO), for Miseq sequencing to analyze the dynamics of community composition of soil CO2-fixing bacteria for five consecutive years after canopy damage. Double treatments of canopy damage and litterfall inputs (TD) facilitate forest restoration better than single treatments (TR or UD). Most soil CO2-fixing bacteria are facultative autotrophic bacteria, and Nitrosospira, Streptomyces, and Saccharomonospora are the main carbon-fixing microorganisms, which have significant differences during the restoration of damaged forest canopy. The forest ecosystem restoration after canopy damage lasted 4–5 years. Rainfall and pH showed a significant negative correlation with most soil CO2-fixing bacteria communities. This study provides a theoretical basis for improving the carbon sequestration capacity of forest soil CO2-fixing bacteria after extreme weather and also provides guidance for forest ecosystem management.
Thermal, Mechanical and Morphological Properties of Cellulose/Lignin Nanocomposites
Authors: Zor Mustafa , Şen Ferhat , Yazıcı Hikmet , Candan Zeki
Published: August 2023

Lignin, a lignocellulosic polymer material, is an important active ingredient for the high-value use of renewable resources. Thus, policies for the recovery and high value-added use of renewable lignocellulosic biomass are a realistic engineering approach to address concerns such as the climate and energy crisis. In this work, the mechanical properties, thermal stability and morphology of cellulose/lignin nanocomposites were studied. Nanocomposite films containing different proportions of lignin (2.5%, 5%, 10% and 20%) were prepared. Thermal properties were assessed via thermogravimetric analysis and differential scanning calorimetry, mechanical properties via tensile test and morphological properties via scanning electron microscopy techniques. It was observed that nanolignin and nanocellulose structures are compatible with each other and depending on the main degradation temperature, the thermal stability of 2.5% lignin-containing nanocomposites is higher than that of other composites. From the results obtained, it was determined that the nanocomposite film containing 2.5% nanolignin had high thermal stability, mechanical strength and suitable morphological structure compared to other samples.
Multiple Factors Jointly Lead to the Lower Soil Microbial Carbon Use Efficiency of Abies fanjingshanensis in a Typical Subtropical Forest in Southwest China
Authors: Wu Xianliang , Zhang Zhenming , Zhang Jiachun , Liu Yingying , Luo Wenmin , Mou Guiting , Huang Xianfei
Published: August 2023

Abies fanjingshanensis trees are the only remaining Abies species in a type of subtropical forest of southwest China and are in imminent danger. Previous studies suggested that the massive death of Abies was caused by the unbalanced chemometrics and nutrients in the soil. To the best of our knowledge, for the first time, we evaluated the microbial carbon use efficiency (CUE) in the rhizospheric topsoil and subsoil of A. fanjingshanensis, at high elevation, middle elevation, and low elevation as well as investigated their physicochemical indices, soil enzyme activities, bacteria, fungi, and microbial biomass. The results showed that the physicochemical parameters (TP, SOC, AK, AP, MC, TN, NO3-N, NH4-N and cation exchange capacity) of the topsoil were higher than those of the subsoil. Acidobacteria, Proteobacteria, Planctomycetes, and Actinobacteria were the dominant phyla in the two soil layers. Candidatus_Koribacter was the main indicator species in the rhizospheric topsoil and subsoil. The positive correlation in the bacterial co-occurrence networks implied that cooperation was dominant between the bacteria in four soil types, and the same phenomenon was found in the co-occurrence networks of fungi. A structural equation model confirmed that pH was the most important factor affecting microbial CUE in the topsoil and subsoil. We inferred that the microorganisms in the acidic soil environment were forced to consume more energy to maintain cellular pH, while less energy was used for growth. The increased solubility of some toxic metals in the acidic soil affected the microbes, resulting in a lower microbial CUE in the A. fanjingshanensis rhizospheric soil. Our results highlight that pH values in soil mainly affected microbial CUE, and a lower microbial CUE may be another important factor in the death of large numbers of A. fanjingshanensis. Several measures must be carried out to improve the microbial CUE in the rhizospheric soil of A. fanjingshanensis by the department of forest management, such as adding the appropriate biochar and nitrogenous fertilizer.
Morphology of Anisotropic Banded Structures in an Emulsion under Simple Shear
Authors: Mateus Jairo Eduardo Leiva , Huesca Marco Antonio Reyes , Lavielle Federico Méndez , Aguilar Enrique Geffroy
Published: August 2023

The formation of flow-induced, oriented structures in two-phase systems, as in this study, is a phenomenon of considerable interest to the scientific and industrial sectors. The main difficulty in understanding the formation of bands of droplets is the simultaneous interplay of physicochemical, hydrodynamic, and mechanical effects. Additionally, banded structure materials frequently show multiple length scales covering several decades as a result of complex time-dependent stress fields. Here, to facilitate understanding a subset of these structures, we studied water in oil emulsions and focused on the effects of three variables specifically: the confinement factor (Co=2R/H), the viscosity ratio (p), and the applied shear rate (γ˙). The confinement (Co) is the ratio between the drop’s diameter (2R) and the separation of (the gap between) the circular rotating disks (H) containing the emulsion. We carried out (a) observations of the induced structure under different simple shear rates, as well as (b) statistical and morphological analysis of these bands. At low shear rates, the system self-assembles into bands along the direction of the flow and stacked normal to the velocity gradient direction. At higher shear rates is possible to observe bands normal to the vorticity direction. Here, we show that a detailed analysis of the dynamics of the band structures is amenable, as well as measurements of flow field anomalies simultaneously observed. The local emulsion viscosity varies in time, increasing in regions of higher droplet concentration and subsequently inducing velocity components perpendicular to the main flow direction. Thus, the emulsion morphology evolves and changes macroscopically. A relatively plausible explanation is attributed to the competitive effects of coalescence and the rupture of drops, where p values less than one predominate coalescence.
The Huntington’s Disease Gene in an Italian Cohort of Patients with Bipolar Disorder
Authors: Ferrari Camilla , Capacci Elena , Bagnoli Silvia , Ingannato Assunta , Sorbi Sandro , Nacmias Benedetta
Published: August 2023

Background and objectives: Huntington’s disease (HD) is characterized by motor, cognitive and psychiatric manifestations and caused by an expansion of CAG repeats over 35 triplets on the huntingtin (HTT) gene. However, expansions in the range 27–35 repeats (intermediate allele) can be associated with pathological phenotypes. The onset of HD is conventionally defined by the onset of motor symptoms, but psychiatric disturbances can precede the motor phase by up to twenty years. The aims of the present study are to identify HD patients in the pre-motor phase of the disease among patients diagnosed with bipolar disorders and evaluate any differences between bipolar patients carrying the normal HTT allele and patients with the expanded HTT gene. Methods: We assessed the HTT genotype in an Italian cohort of 69 patients who were affected by either type 1 or type 2 bipolar disorder. Results: No patient was found to be a carrier of the pathological HTT allele, but 10% of bipolar subjects carried an intermediate allele. Carriers of the intermediate allele were older at the onset of psychiatric symptoms than non-carriers. Conclusion: The pathological HTT gene was not associated with bipolar disorder, while we found a higher frequency of the intermediate allele among the bipolar population with respect to healthy controls. The identification of this subset of bipolar subjects has implications for the clinical management of patients and their family members and promotes further investigation into possible pathological mechanisms common to both HD and bipolar disorder.
Optical Genome Mapping: Integrating Structural Variations for Precise Homologous Recombination Deficiency Score Calculation
Authors: Sahajpal Nikhil Shri , Mondal Ashis K. , Vashisht Ashutosh , Singh Harmanpreet , Pang Andy Wing Chun , Saul Daniel , Nivin Omar , Hilton Benjamin , DuPont Barbara R. , Kota Vamsi , Savage Natasha M. , Hastie Alex R. , Chaubey Alka , Kolhe Ravindra
Published: August 2023

Homologous recombination deficiency (HRD) is characterized by the inability of a cell to repair the double-stranded breaks using the homologous recombination repair (HRR) pathway. The deficiency of the HRR pathway results in defective DNA repair, leading to genomic instability and tumorigenesis. The presence of HRD has been found to make tumors sensitive to ICL-inducing platinum-based therapies and poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitors (PARPi). However, there are no standardized methods to measure and report HRD phenotypes. Herein, we compare optical genome mapping (OGM), chromosomal microarray (CMA), and a 523-gene NGS panel for HRD score calculations. This retrospective study included the analysis of 196 samples, of which 10 were gliomas, 176 were hematological malignancy samples, and 10 were controls. The 10 gliomas were evaluated with both CMA and OGM, and 30 hematological malignancy samples were evaluated with both the NGS panel and OGM. To verify the scores in a larger cohort, 135 cases were evaluated with the NGS panel and 71 cases with OGM. The HRD scores were calculated using a combination of three HRD signatures that included loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale transitions (LST). In the ten glioma cases analyzed with OGM and CMA using the same DNA (to remove any tumor percentage bias), the HRD scores (mean ± SEM) were 13.2 (±4.2) with OGM compared to 3.7 (±1.4) with CMA. In the 30 hematological malignancy cases analyzed with OGM and the 523-gene NGS panel, the HRD scores were 7.6 (±2.2) with OGM compared to 2.6 (±0.8) with the 523-gene NGS panel. OGM detected 70.8% and 66.8% of additional variants that are considered HRD signatures in gliomas and hematological malignancies, respectively. The higher sensitivity of OGM to capture HRD signature variants might enable a more accurate and precise correlation with response to PARPi and platinum-based drugs. This study reveals HRD signatures that are cryptic to current standard of care (SOC) methods used for assessing the HRD phenotype and presents OGM as an attractive alternative with higher resolution and sensitivity to accurately assess the HRD phenotype.
Genome-Wide Association Study Reveals the Genetic Basis of Total Flavonoid Content in Brown Rice
Authors: Xia Haijian , Pu Xiaoying , Zhu Xiaoyang , Yang Xiaomeng , Guo Haifeng , Diao Henan , Zhang Quan , Wang Yulong , Sun Xingming , Zhang Hongliang , Zhang Zhanying , Zeng Yawen , Li Zichao
Published: August 2023

Flavonoids have anti-inflammatory, antioxidative, and anticarcinogenic effects. Breeding rice varieties rich in flavonoids can prevent chronic diseases such as cancer and cardio-cerebrovascular diseases. However, most of the genes reported are known to regulate flavonoid content in leaves or seedlings. To further elucidate the genetic basis of flavonoid content in rice grains and identify germplasm rich in flavonoids in grains, a set of rice core collections containing 633 accessions from 32 countries was used to determine total flavonoid content (TFC) in brown rice. We identified ten excellent germplasms with TFC exceeding 300 mg/100 g. Using a compressed mixed linear model, a total of 53 quantitative trait loci (QTLs) were detected through a genome-wide association study (GWAS). By combining linkage disequilibrium (LD) analysis, location of significant single nucleotide polymorphisms (SNPs), gene expression, and haplotype analysis, eight candidate genes were identified from two important QTLs (qTFC1-6 and qTFC9-7), among which LOC_Os01g59440 and LOC_Os09g24260 are the most likely candidate genes. We also analyzed the geographic distribution and breeding utilization of favorable haplotypes of the two genes. Our findings provide insights into the genetic basis of TFC in brown rice and could facilitate the breeding of flavonoid-rich varieties, which may be a prevention and adjuvant treatment for cancer and cardio-cerebrovascular diseases.
3′ UTR Deletion of FBXO28 in a Patient with Brain Abnormalities and Developmental Delay
Authors: Bi Xin , Mulhern Maureen S. , Spiegel Erica , Wapner Ronald J. , Levy Brynn , Bain Jennifer M. , Liao Jun
Published: August 2023

Constitutional deletions of chromosome 1q42 region are rare. The phenotype spectrum associated with this copy number change is variable, including developmental delay, intellectual disability, seizures, and dysmorphology. This study describes a patient with developmental delays and brain abnormalities. G-banded karyotype, FISH, SNP oligonucleotide microarray analysis (SOMA), and whole exome sequencing analysis were performed. Postnatal reanalysis of prenatal SOMA and follow-up parental testing revealed a paternally inherited 63 kb deletion at 1q42.11 in the patient. We characterized the clinical features of this patient, providing insight into the clinical phenotype associated with deletions of the 1q42.11 sub-band. Our study provides new evidence supporting the potential functional importance of the FBXO28 3′ UTR region and the hypothesis that FBXO28 is a critical gene in the pathogenesis of chromosome 1q41q42 microdeletion syndrome. It also highlights the different goals and reporting criteria between prenatal and postnatal microarray tests.
Vitamin D: An Overview of Gene Regulation, Ranging from Metabolism to Genomic Effects
Authors: Voltan Giacomo , Cannito Michele , Ferrarese Michela , Ceccato Filippo , Camozzi Valentina
Published: August 2023

Vitamin D is a pro-hormone characterized by an intricate metabolism and regulation. It is well known for its role in calcium and phosphate metabolism, and in bone health. However, several studies have assessed a huge number of extra-skeletal functions, ranging from cell proliferation in some oncogenic pathways to antioxidant and immunomodulatory functions. Vitamin D exerts its role by binding to VDRs (vitamin D receptors), which are located in many different tissues. Moreover, VDRs are able to bind hundreds of genomic loci, modulating the expression of various primary target genes. Interestingly, plenty of gene polymorphisms regarding VDRs are described, each one carrying a potential influence against gene expression, with relapses in several chronic diseases and metabolic complications. In this review, we provide an overview of the genetic aspects of vitamin D and VDR, emphasizing the gene regulation of vitamin D, and the genetic modulation of VDR target genes. In addition, we briefly summarize the rare genetic disease linked to vitamin D metabolism.
Insights into Late Quaternary Rock Shelter Sedimentation at Santuario Della Madonna Cave (Northern Calabria, Italy)
Authors: Robustelli Gaetano , Lucà Federica
Published: August 2023

Shelter caves serve as crucial repositories that provide valuable insights into Late Pleistocene–Holocene depositional mechanisms and environmental changes. In this study, we conducted a stratigraphic analysis of the easternmost cave-fill succession within the Santuario della Madonna cave, located along the Tyrrhenian coasts of southern Italy. By examining the cave-fill deposits and their relationship with archaeological successions from previous excavation campaigns, we aimed to enhance our understanding of sedimentary evolution, specifically, the interplay between local and global environmental factors. A comprehensive sedimentological analysis was conducted, enabling the identification of three distinct sedimentary facies within the clastic succession that overlays the calcareous cave roof. Our findings reveal a noticeable shift in cave sedimentation processes, characterized by a gap in detritus accumulation followed by the deposition of flowstones. Furthermore, the presence of oversized boulders within the succession was attributed to failures from the cliffs that overhang the cave opening. We interpret these boulders as possible evidence of cave collapses induced by earthquakes, similarly to rockfall phenomena observed in the archaeological test pits within the shelter, which show a strong correlation with paleoseismic events.
Making Capital of ‘Illegal’ Publication under Japanese Imperial Censorship: Publication Strategies of Senki (Battle Flag) around 1930
Authors: Ko Young Ran , Ogonek Nick , Choi Kyeong-Hee
Published: August 2023

Around 1930, the Japanese publishing market was restructured, and as part of this process, the colonial market emerged within the Japanese Empire. In an attempt to expand into the colonial market, publishers such as Kaizō-sha, Chūōkōron-sha, and Senki-sha competed among each other, producing ‘legal’ and ‘illegal’ commodities related to socialism. This paper examines the circulation of illegal commodities such as the often-banned magazine Senki (Battle Flag), cross-reading them with internal documents from Senki-sha (Senki’s publisher) and NAPF (All-Japan Federation of Proletarian Arts), as well as with those from the Japanese Home Ministry and the Japanese Government-General in Korea. By doing so, the essay argues that the main actors of the socialist cultural movement around 1930 purposefully planned to capitalize on the ‘illegal’ nature of their commodities, while adopting a public stance of differentiation from commercial capital. Furthermore, by proposing that the publication of illegal commodities was in fact deeply imbricated with the movement of capital in the publishing market, this paper also reveals that Korean-language publications–notably, the magazine Uri tongmu (Our Comrades)–produced by socialists in the Japanese interior around 1930, ended up playing a role in undermining the reconstruction of socialism in Korea. For this reason, it is crucial to reconsider the prevailing narrative about the history of the Japanese socialist movement of the late 1920s and early 1930s, which often essentializes the connection between Japanese and Korean socialists as pure ideological solidarity, paying little attention to the complex movement of capital, legal and illegal, at work in the Japanese Empire around 1930.
Effect of Ozone Stresses on Growth and Secondary Plant Metabolism of Brassica campestris L. ssp. chinensis
Authors: Han Young Jong , Beck Winston , Mewis Inga , Förster Nadja , Ulrichs Christian
Published: August 2023

Determining plant responses to hazardous air pollutants is critical in predicting food security programs and challenges in the future. This study aimed to determine the effects of various ozone levels on plant growth responses (leaf area, dry matter, and number of leaves) and biochemical quality (photopigments and glucosinolates) on Brassica campestris L. ssp. chinensis (Pak-Choi). The experiment was conducted within test chambers under different ozone concentrations (60, 150, and 240 ppb for 2 h/day). Leaf area and dry matter were negatively correlated with increasing ozone concentrations, but the number of leaves was not affected by ozone treatment. Lycopene and chlorophylls also showed the same tendency. Even if the ambient ozone concentration was only elevated for a short time, various glucosnilates (GLS) have been diversely affected. The total aliphatic GLS content was reduced. In contrast, the total indole GLS increased at the highest ozone concentration, and the aromatic GLS significantly increased and then decreased as the ozone concentration level increased. These results provide evidence of the strong effect of ozone stress on the plant quality of Pak-Choi with respect to certain secondary plant metabolites. These findings provide an understanding of elevated ozone effects in urban horticulture sites on the growth and metabolite profiling of Brassica plants.
Incorporating Monoclonal Antibodies into the First-Line Treatment of Classical Hodgkin Lymphoma
Authors: Vassilakopoulos Theodoros P. , Liaskas Athanasios , Pereyra Patricio , Panayiotidis Panayiotis , Angelopoulou Maria K. , Gallamini Andrea
Published: August 2023

The long-term survival of Hodgkin lymphoma (HL) patients treated according to the current standard of care is excellent. Combined-modality schedules (ABVD plus radiotherapy) in early-stage disease, along with treatment intensity adaptation to early metabolic response assessed by PET/CT in advanced stage HL, have been the cornerstones of risk stratification and treatment decision-making, minimizing treatment-related complications while keeping efficacy. Nevertheless, a non-negligible number of patients are primary refractory or relapse after front-line treatment. Novel immunotherapeutic agents, namely Brentuximab Vedotin (BV) and immune checkpoint inhibitors (CPI), have already shown outstanding efficacy in a relapsed/refractory setting in recent landmark studies. Several phase 2 single-arm studies suggest that the addition of these agents in the frontline setting could further improve long-term disease control permitting one to reduce the exposure to cytotoxic drugs. However, a longer follow-up is needed. At the time of this writing, the only randomized phase 3 trial so far published is the ECHELON-1, which compares 1 to 1 BV-AVD (Bleomycin is replaced by BV) with standard ABVD in untreated advanced-stage III and IV HL. The ECHELON-1 trial has proven that BV-AVD is safe and more effective both in terms of long-term disease control and overall survival. Just recently, the results of the S1826 SWOG trial demonstrated that the combination nivolumab-AVD (N-AVD) is better than BV-AVD, while preliminary results of other randomized ongoing phase 3 trials incorporating anti-PD-1 in this setting will be soon available. The aim of this review is to present the recent data regarding these novel agents in first-line treatment of HL and to highlight current and future trends which will hopefully reshape the overall management of this disease.
Pluripotential GluN1 (NMDA NR1): Functional Significance in Cellular Nuclei in Pain/Nociception
Authors: McNearney Terry A. , Westlund Karin N.
Published: August 2023

The N-methyl-D-aspartate (NMDA) glutamate receptors function as plasma membrane ionic channels and take part in very tightly controlled cellular processes activating neurogenic and inflammatory pathways. In particular, the NR1 subunit (new terminology: GluN1) is required for many neuronal and non-neuronal cell functions, including plasticity, survival, and differentiation. Physiologic levels of glutamate agonists and NMDA receptor activation are required for normal neuronal functions such as neuronal development, learning, and memory. When glutamate receptor agonists are present in excess, binding to NMDA receptors produces neuronal/CNS/PNS long-term potentiation, conditions of acute pain, ongoing severe intractable pain, and potential excitotoxicity and pathology. The GluNR1 subunit (116 kD) is necessary as the anchor component directing ion channel heterodimer formation, cellular trafficking, and the nuclear localization that directs functionally specific heterodimer formation, cellular trafficking, and nuclear functions. Emerging studies report the relevance of GluN1 subunit composition and specifically that nuclear GluN1 has major physiologic potential in tissue and/or subnuclear functioning assignments. The shift of the GluN1 subunit from a surface cell membrane to nuclear localization assigns the GluN1 promoter immediate early gene behavior with access to nuclear and potentially nucleolar functions. The present narrative review addresses the nuclear translocation of GluN1, focusing particularly on examples of the role of GluN1 in nociceptive processes.
Novel Electroactive Mineralized Polyacrylonitrile/PEDOT:PSS Electrospun Nanofibers for Bone Repair Applications
Authors: Barbosa Frederico , Garrudo Fábio F. F. , Marques Ana C. , Cabral Joaquim M. S. , Morgado Jorge , Ferreira Frederico Castelo , Silva João C.
Published: August 2023

Bone defect repair remains a critical challenge in current orthopedic clinical practice, as the available therapeutic strategies only offer suboptimal outcomes. Therefore, bone tissue engineering (BTE) approaches, involving the development of biomimetic implantable scaffolds combined with osteoprogenitor cells and native-like physical stimuli, are gaining widespread interest. Electrical stimulation (ES)-based therapies have been found to actively promote bone growth and osteogenesis in both in vivo and in vitro settings. Thus, the combination of electroactive scaffolds comprising conductive biomaterials and ES holds significant promise in improving the effectiveness of BTE for clinical applications. The aim of this study was to develop electroconductive polyacrylonitrile/poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PAN/PEDOT:PSS) nanofibers via electrospinning, which are capable of emulating the native tissue’s fibrous extracellular matrix (ECM) and providing a platform for the delivery of exogenous ES. The resulting nanofibers were successfully functionalized with apatite-like structures to mimic the inorganic phase of the bone ECM. The conductive electrospun scaffolds presented nanoscale fiber diameters akin to those of collagen fibrils and displayed bone-like conductivity. PEDOT:PSS incorporation was shown to significantly promote scaffold mineralization in vitro. The mineralized electroconductive nanofibers demonstrated improved biological performance as observed by the significantly enhanced proliferation of both human osteoblast-like MG-63 cells and human bone marrow-derived mesenchymal stem/stromal cells (hBM-MSCs). Moreover, mineralized PAN/PEDOT:PSS nanofibers up-regulated bone marker genes expression levels of hBM-MSCs undergoing osteogenic differentiation, highlighting their potential as electroactive biomimetic BTE scaffolds for innovative bone defect repair strategies.
The Association between Vascular Abnormalities and Glaucoma—What Comes First?
Authors: Wang Xiaosha , Wang Maoren , Liu Hanhan , Mercieca Karl , Prinz Julia , Feng Yuan , Prokosch Verena
Published: August 2023

Glaucoma is a leading cause of irreversible blindness worldwide. While intraocular pressure (IOP) presents a major risk factor, the underlying pathophysiology still remains largely unclear. The correlation between vascular abnormalities and glaucoma has been deliberated for decades. Evidence for a role played by vascular factors in the pathogenesis of glaucomatous neurodegeneration has already been postulated. In addition, the fact that glaucoma causes both structural and functional changes to retinal blood vessels has been described. This review aims to investigate the published evidence concerning the relationship between vascular abnormalities and glaucoma, and to provide an overview of the “chicken or egg” dilemma in glaucoma. In this study, several biomarkers of glaucoma progression from a vascular perspective, including endothelin-1 (ET-1), nitric oxide, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs), were identified and subsequently assessed for their potential as pharmacological intervention targets.
Hallmarks of the Tumour Microenvironment of Gliomas and Its Interaction with Emerging Immunotherapy Modalities
Authors: Linares Christian A. , Varghese Anjana , Ghose Aruni , Shinde Sayali D. , Adeleke Sola , Sanchez Elisabet , Sheriff Matin , Chargari Cyrus , Rassy Elie , Boussios Stergios
Published: August 2023

Gliomas are aggressive, primary central nervous system tumours arising from glial cells. Glioblastomas are the most malignant. They are known for their poor prognosis or median overall survival. The current standard of care is overwhelmed by the heterogeneous, immunosuppressive tumour microenvironment promoting immune evasion and tumour proliferation. The advent of immunotherapy with its various modalities—immune checkpoint inhibitors, cancer vaccines, oncolytic viruses and chimeric antigen receptor T cells and NK cells—has shown promise. Clinical trials incorporating combination immunotherapies have overcome the microenvironment resistance and yielded promising survival and prognostic benefits. Rolling these new therapies out in the real-world scenario in a low-cost, high-throughput manner is the unmet need of the hour. These will have practice-changing implications to the glioma treatment landscape. Here, we review the immunobiological hallmarks of the TME of gliomas, how the TME evades immunotherapies and the work that is being conducted to overcome this interplay.
The Role of Echocardiography and Cardiac Computed Tomography in Diagnosis of Infective Endocarditis
Authors: Petkovic Ana , Menkovic Nemanja , Petrovic Olga , Bilbija Ilija , Radovanovic Nikola N. , Stanisavljevic Dejana , Putnik Svetozar , Maksimovic Ruzica , Ivanovic Branislava
Published: August 2023

Background: Infective endocarditis (IE) is a rare disease with a high mortality rate and rising incidence, requiring timely and precise diagnosis in order to choose appropriate therapy. Imaging of morphologic lesions is an integrative part of diagnosis. Artifacts and the patient’s habitus make echocardiography difficult to visualize advanced-form IE. Cardiac computed tomography (CCT) constantly shows an additive diagnostic value due to high resolution of cardiac anatomy. Conjecturally, joint application of both diagnostic tests improves overall sensitivity and specificity in diagnosing IE. Methods: Patients with definite IE underwent transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), and CCT. We analyzed valvular and paravalvular IE lesions in all three imaging methods and compared them to surgical or autopsy findings. We calculated sensitivity, specificity, diagnostic accuracy, and positive and negative predictive value of both imaging tests individually and jointly used. Results: We examined 78 patients, male to female ratio 2:1, mean age 52.29 ± 16.62. We analyzed 85 valves, 70 native valves, 13 prosthetic valves, and 2 corrected valves due to Ozaki procedure, along with a central shunt and 4 pacemaker leads. As a single test, the sensitivity and specificity of CCT, TTE, and TEE for valvular lesions were 91.6/20%, 65.5/57.9%, and 60/84%, and paravalvular lesions were 100/0%, 46/10.5%, and 14.7/100%. When combined together, sensitivity and specificity for valvular lesions rose to 96.6/0% and paravalvular lesions to 100/0%. We also analyzed the diagnostic performance for each test in single and mutual application, per specific IE lesion. Conclusion: In the individual application, CCT in comparison to TTE and TEE shows better diagnostic performance in detection of valvular and paravalvular lesions. In joint application, there is a statistically significant difference in performance compared to their single use, especially in prosthetic valves and invasive forms of IE native valves.
The Complexities of Diagnosis with Co-Existing Gaucher Disease and Hemato-Oncology—A Case Report and Review of the Literature
Authors: Sudul Paulina , Piatkowska-Jakubas Beata , Pawlinski Lukasz , Galazka Krystyna , Sacha Tomasz , Kiec-Wilk Beata
Published: August 2023

Hematological abnormalities are the most common early symptoms of Gaucher disease (GD), with an increased risk of hematopoietic system malignancies reported in patients with GD. GD may be associated with monoclonal and polyclonal gammopathies; however, the mechanism of association of GD with multiple myeloma (MM) remains uncertain. Enzyme replacement therapy (ERT) has been shown to improve patients’ cytopenia and it seems to facilitate anti-myeloma therapy in patients with co-occurring GD and MM. Although it is necessary to demonstrate the deficiency of enzymatic activity, as well as using genetic tests to finally diagnose GD, due to changes in the blood count image, bone marrow biopsy is still a frequent element of the GD diagnosis procedure. The diagnosis of GD is often delayed, mainly due to the heterogeneity of the histopathological picture of bone marrow biopsy or overlapping hematological abnormalities. Unrecognized and untreated GD worsens the response of a patient with an oncological disease to targeted treatment. We present a literature review, inspired by the case of a Caucasian patient initially diagnosed with MM and later confirmed with comorbid GD type 1 (GD1). We would like to point out the problem of underdiagnosis and delay in patients with GD.
Is Serum 25-Hydroxyvitamin D Level Associated with Severity of COVID-19? A Retrospective Study
Authors: Mbata Munachimso Kizito , Hunziker Mireille , Makhdoomi Anja , Lüthi-Corridori Giorgia , Boesing Maria , Giezendanner Stéphanie , Muser Jürgen , Leuppi-Taegtmeyer Anne B. , Leuppi Jörg D.
Published: August 2023

(1) Background: SARS-COV2 infection has a clinical spectrum ranging from asymptomatic infection to COVID-19 with acute respiratory distress syndrome (ARDS). Although vitamin D deficiency is often found in patients with ARDS, its role in COVID-19 is not clear. The aim of this study was to explore a possible association between serum 25-hydroxyvitamin D levels and the severity of COVID-19 in hospitalised patients. (2) Methods: In this retrospective observational study, we analysed data from 763 patients hospitalised for COVID-19 in 2020 and 2021. Patients were included in the study if serum 25-hydroxyvitamin D was assessed 30 days before or after hospital admission. Vitamin D deficiency was defined as <50 nmol/L (<20 ng/mL). The primary outcome was COVID-19 severity. (3) Results: The overall median serum 25-hydroxyvitamin D level was 54 nmol/L (IQR 35–76); 47% of the patients were vitamin D deficient. Most patients had mild to moderate COVID-19 and no differences were observed between vitamin D deficient and non-deficient patients (81% vs. 84% of patients, respectively p = 0.829). (4) Conclusion: No association was found between serum 25-hydroxyvitamin D levels and COVID-19 severity in this large observational study conducted over 2 years of the pandemic.
Association between Hospital-Acquired Pneumonia and In-Hospital Mortality in Solid Organ Transplant Admissions: An Observational Analysis in Spain, 2004–2021
Authors: de-Miguel-Yanes José M. , Lopez-de-Andres Ana , Jimenez-Garcia Rodrigo , Zamorano-Leon José Javier , Carabantes-Alarcon David , Omaña-Palanco Ricardo , Hernández-Barrera Valentín , del-Barrio Jose Luis , de-Miguel-Diez Javier , Cuadrado-Corrales Natividad
Published: August 2023

(1) Background: To analyze the association between hospital-acquired pneumonia (HAP) and in-hospital mortality (IHM) during hospital admission for solid organ transplant in Spain during 2004–2021. (2) Methods: We used national hospital discharge data to select all hospital admissions for kidney, liver, heart, and lung transplants. We stratified the data according to HAP status. To examine time trends, we grouped data into three consecutive 6-year periods (2004–2009; 2010–2015; and 2016–2021). We assessed in-hospital mortality (IHM) in logistic regression analyses and obtained odds ratios (ORs) with their 95% confidence intervals (CIs). (3) Results: We identified a total of 71,827 transplants (45,262, kidney; 18,127, liver; 4734, heart; and 4598, lung). Two thirds of the patients were men. Overall, the rate of HAP during admission was 2.6% and decreased from 3.0% during 2004–2009 to 2.4% during 2016–2021. The highest rate of HAP corresponded to lung transplant (9.4%), whereas we found the lowest rate for kidney transplant (1.1%). Rates of HAP for liver and heart transplants were 3.8% and 6.3%, respectively. IHM was significantly lower during 2016–2021 compared to 2004–2009 for all types of transplants (ORs (CIs) = 0.65 (0.53–0.79) for kidney; 0.73 (0.63–0.84) for liver; 0.72 (0.59–0.87) for heart; and 0.39 (0.31–0.47) for lung). HAP was associated with IHM for all types of transplants (ORs (CIs) = 4.47 (2.85–9.08) for kidney; 2.96 (2.34–3.75) for liver; 1.86 (1.34–2.57) for heart; and 2.97 (2.24–3.94) for lung). (4) Conclusions: Rates of HAP during admission for solid organ transplant differ depending on the type of transplant. Although IHM during admission for solid organ transplant has decreased over time in our country, HAP persists and is associated with a higher IHM after accounting for potential confounding variables.
Atopic Dermatitis: Beyond the Skin and Into the Gut
Authors: Sadowsky Rachel L. , Sulejmani Pranvera , Lio Peter A.
Published: August 2023

Atopic dermatitis (AD) is a common, chronic and recurring inflammatory skin disorder characterized by an intensely pruritic, eczematous dermatitis. The etiology of AD is thought to involve a combination of environmental, genetic, and immunologic factors. Emerging research has investigated factors that may impact individual risk for developing AD, disease severity, and treatment response. One component is the gut microbiome, which is considered to play an essential role in maintaining the homeostasis of several organ systems. The gut microbiome has been described as a major regulator of the “gut–skin axis,” yet some studies have yielded conflicting evidence regarding the strength of the association of gut microbiota dysbiosis with AD. This review discusses recent insights into the role of the gut microbiome in AD pathogenesis and its interplay among other complex systems that govern the current assessments of and treatments for AD.
When Bladder and Brain Collide: Is There a Gender Difference in the Relationship between Urinary Incontinence, Chronic Depression, and Anxiety?
Authors: Dasdelen Muhammed Furkan , Almas Furkan , Celik Suleyman , Celik Nursanem , Seyhan Zuleyha , Laguna Pilar , Albayrak Selami , Horuz Rahim , Kocak Mehmet , de la Rosette Jean
Published: August 2023

In longitudinal and cross-sectional studies, depression and anxiety have been associated with urinary incontinence (UI) in women. However, this association has not been studied in men. Utilizing data from the 2008 Turkish Health Studies Survey conducted by the Turkish Statistical Institute, we analyzed 13,830 participants aged 15 years and above. We investigated the association of UI with psychological discomfort in both sexes using multivariable logistic regression. High psychological discomfort significantly correlated with UI in males (OR 2.30, 95% CI 1.43–3.71) and females (OR 2.78, 95% CI 1.80–4.29). Anxiety increased UI likelihood in females (OR 2.36, 95% CI 1.61–3.46) and males (OR 2.37, 95% CI 1.10–5.13). Depression related significantly to UI in females (OR 2.54, 95% CI 1.81–3.58) but not males (OR 1.63, 95% CI 0.71–3.76). Antidepressant and anxiolytic use was not significantly related to UI in either gender. Anxiety and psychological discomfort contribute to UI in both genders. While depression significantly correlates with UI in females, it does not show the same magnitude and significance in males. Antidepressant and anxiolytic use did not significantly influence the association. These findings underscore the psychological distress-UI link, advocating a holistic approach for managing UI in individuals with mental health conditions.
A Review of Recent Improvements, Developments, Effects, and Challenges on Using Phase-Change Materials in Concrete for Thermal Energy Storage and Release
Authors: Rashid Farhan , Al-Obaidi Mudhar , Dulaimi Anmar , Bernardo Luís , Eleiwi Muhammad , Mahood Hameed , Hashim Ahmed
Published: August 2023

Most concrete employs organic phase change materials (PCMs), although there are different types available for more specialised use. Organic PCMs are the material of choice for concrete due to their greater heat of fusion and lower cost in comparison to other PCMs. Phase transition materials are an example of latent heat storage materials (LHSMs) that may store or release thermal energy at certain temperatures. A phase transition occurs when a solid material changes from a solid state to a liquid state and back again when heat is added or removed. It is common knowledge that adding anything to concrete, including PCMs, will affect its performance. The goal of this review is to detail the ways in which PCMs affect certain concrete features. This overview also looks into the current challenges connected with employing PCMs in concrete. The review demonstrates a number of important findings along with the possible benefits that may pave the way for more research and broader applications of PCMs in construction. More importantly, it has been elucidated that the optimum PCM integrated percentage of 40% has doubled the quantity of thermal energy stored and released in concrete. Compared to conventional concrete, the macro-encapsulated PCMs showed thermal dependability, chemical compatibility, and thermal stability due to delaying temperature peaks. Furthermore, the maximum indoor temperature decreases by 1.85 °C and 3.76 °C in the test room due to the addition of 15% and 30% PCM composite, respectively. Last but not least, incorporating microencapsulated PCM has shown a positive effect on preventing freeze-thaw damage to concrete roads.
Review on Characterization of Biochar Derived from Biomass Pyrolysis via Reactive Molecular Dynamics Simulations
Authors: Hu Zhong , Wei Lin
Published: August 2023

Biochar is a carbon-rich solid produced during the thermochemical processes of various biomass feedstocks. As a low-cost and environmentally friendly material, biochar has multiple significant advantages and potentials, and it can replace more expensive synthetic carbon materials for many applications in nanocomposites, energy storage, sensors, and biosensors. Due to biomass feedstock species, reactor types, operating conditions, and the interaction between different factors, the compositions, structure and function, and physicochemical properties of the biochar may vary greatly, traditional trial-and-error experimental approaches are time consuming, expensive, and sometimes impossible. Computer simulations, such as molecular dynamics (MD) simulations, are an alternative and powerful method for characterizing materials. Biomass pyrolysis is one of the most common processes to produce biochar. Since pyrolysis of decomposing biomass into biochar is based on the bond-order chemical reactions (the breakage and formation of bonds during carbonization reactions), an advanced reactive force field (ReaxFF)-based MD method is especially effective in simulating and/or analyzing the biomass pyrolysis process. This paper reviewed the fundamentals of the ReaxFF method and previous research on the characterization of biochar physicochemical properties and the biomass pyrolysis process via MD simulations based on ReaxFF. ReaxFF implicitly describes chemical bonds without requiring quantum mechanics calculations to disclose the complex reaction mechanisms at the nano/micro scale, thereby gaining insight into the carbonization reactions during the biomass pyrolysis process. The biomass pyrolysis and its carbonization reactions, including the reactivity of the major components of biomass, such as cellulose, lignin, and hemicellulose, were discussed. Potential applications of ReaxFF MD were also briefly discussed. MD simulations based on ReaxFF can be an effective method to understand the mechanisms of chemical reactions and to predict and/or improve the structure, functionality, and physicochemical properties of the products.
Role of the Lactide:Glycolide Ratio in PLGA Nanoparticle Stability and Release under Lysosomal Conditions for Enzyme Replacement Therapy of Lysosomal Storage Disorders
Authors: del Moral Maria , Loeck Maximilian , Muntimadugu Eameema , Vives Guillem , Pham Vy , Pfeifer Peter , Battaglia Giuseppe , Muro Silvia
Published: August 2023

Prior studies demonstrated that encapsulation in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) enhanced the delivery of enzymes used for replacement therapy (ERT) of lysosomal storage disorders (LSDs). This study examined how the copolymer lactide:glycolide ratio impacts encapsulation, physicochemical characteristics, stability, and release under lysosomal conditions. Hyaluronidase, deficient in mucopolysaccharidosis IX, was encapsulated in NPs synthesized using 50:50, 60:40, or 75:25 lactide:glycolide copolymers. All NPs had diameters compatible with cellular transport (≤168 nm) and polydispersity indexes (≤0.16) and ζ-potentials (≤−35 mV) compatible with colloidal stability. Yet, their encapsulation efficiency varied, with 75:25 NPs and 60:40 NPs having the lowest and highest EE, respectively (15% vs. 28%). Under lysosomal conditions, the 50:50 copolymer degraded fastest (41% in 1 week), as expected, and the presence of a targeting antibody coat did not alter this result. Additionally, 60:40 NPs destabilized fastest (<1 week) because of their smaller diameter, and 75:25 NPs did not destabilize in 4 weeks. All formulations presented burst release under lysosomal conditions (56–78% of the original load within 30 min), with 50:50 and 60:40 NPs releasing an additional small fraction after week 1. This provided 4 weeks of sustained catalytic activity, sufficient to fully degrade a substrate. Altogether, the 60:40 NP formulation is preferred given its higher EE, and 50:50 NPs represent a valid alternative, while the highest stability of 75:25 NPs may impair lysosomes. These results can guide future studies aiming to translate PLGA NP-based ERT for this and other LSDs.
Influence of Sheet Covers on Filling Behavior in Electrochemical Joining of Additively Manufactured Components
Authors: Noack Marco , Rudolph Kris , Breimann Richard , Kirchner Eckhard
Published: August 2023

This paper focuses on the electrochemical joining of additively manufactured components using simulation-based and experimental methods. The study investigates the influence of cover screens on the filling behavior of the joining zone. Experimental methods involving additive manufacturing and electroplating are combined with simulation models to provide a realistic representation of the joining process. The results show a good agreement between the simulated and experimental findings, indicating the applicability of the simulation model. The parameter study reveals that higher cover factors result in a decrease in the excess material ratio, indicating reduced material deposition outside the joining zone. The filling time required to completely fill the joining zone is influenced by both the cover size and the opening angle of the joining zone. The optimal parameter combinations depend on whether the filling time or the excess material volume is to be minimized. Cavity formation within the joining zone was identified as a critical factor affecting the completeness of the filling. The study provides insights into the influence of cover screens on the electrochemical joining process and offers guidance for optimizing the design of the joining zone.