bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomics-Based Identification of Retinal Protein Networks Impacted by Elevated Intraocular Pressure in the Hypertonic Saline Injection Model of Experimental Glaucoma
Authors: Zaman Khadiza , Nguyen Vien , Prokai-Tatrai Katalin , Prokai Laszlo
Published: August 2023

Elevated intraocular pressure is considered a major cause of glaucomatous retinal neurodegeneration. To facilitate a better understanding of the underlying molecular processes and mechanisms, we report a study focusing on alterations of the retina proteome by induced ocular hypertension in a rat model of the disease. Glaucomatous processes were modeled through sclerosing the aqueous outflow routes of the eyes by hypertonic saline injections into an episcleral vein. Mass spectrometry-based quantitative retina proteomics using a label-free shotgun methodology identified over 200 proteins significantly affected by ocular hypertension. Various facets of glaucomatous pathophysiology were revealed through the organization of the findings into protein interaction networks and by pathway analyses. Concentrating on retinal neurodegeneration as a characteristic process of the disease, elevated intraocular pressure-induced alterations in the expression of selected proteins were verified by targeted proteomics based on nanoflow liquid chromatography coupled with nano-electrospray ionization tandem mass spectrometry using the parallel reaction monitoring method of data acquisition. Acquired raw data are shared through deposition to the ProteomeXchange Consortium (PXD042729), making a retina proteomics dataset on the selected animal model of glaucoma available for the first time.
Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development
Authors: Günter Alexander , Sothilingam Vithiyanjali , Orlich Michael M. , Nordheim Alfred , Seeliger Mathias W. , Mühlfriedel Regine
Published: August 2023

Serum response factor (SRF) controls the expression of muscle contraction and motility genes in mural cells (MCs) of the vasculature. In the retina, MC-SRF is important for correct angiogenesis during development and the continuing maintenance of the vascular tone. The purpose of this study was to provide further insights into the effects of MC SRF deficiency on the vasculature and function of the mature retina in SrfiMCKO mice that carry a MC-specific deletion of Srf. Retinal morphology and vascular integrity were analyzed in vivo via scanning laser ophthalmoscopy (SLO), angiography, and optical coherence tomography (OCT). Retinal function was evaluated with full-field electroretinography (ERG). We found that retinal blood vessels of these mutants exhibited different degrees of morphological and functional alterations. With increasing severity, we found vascular bulging, the formation of arteriovenous (AV) anastomoses, and ultimately, a retinal detachment (RD). The associated irregular retinal blood pressure and flow distribution eventually induced hypoxia, indicated by a negative ERG waveform shape. Further, the high frequency of interocular differences in the phenotype of individual SrfiMCKO mice points to a secondary nature of these developments far downstream of the genetic defect and rather dependent on the local retinal context.
Sex-Dependent Altered Expression of Cannabinoid Signaling in Hippocampal Astrocytes of the Triple Transgenic Mouse Model of Alzheimer’s Disease: Implications for Controlling Astroglial Activity
Authors: Pacheco-Sánchez Beatriz , Tovar Rubén , Ben Rabaa Meriem , Sánchez-Salido Lourdes , Vargas Antonio , Suárez Juan , Rodríguez de Fonseca Fernando , Rivera Patricia
Published: August 2023

Alzheimer’s disease (AD) is a common neurodegenerative disease. In AD-associated neuroinflammation, astrocytes play a key role, finding glial activation both in patients and in animal models. The endocannabinoid system (ECS) is a neurolipid signaling system with anti-inflammatory and neuroprotective properties implicated in AD. Astrocytes respond to external cannabinoid signals and also have their own cannabinoid signaling. Our main objective is to describe the cannabinoid signaling machinery present in hippocampal astrocytes from 3×Tg-AD mice to determine if they are actively involved in the neurodegenerative process. Primary cultures of astrocytes from the hippocampus of 3×Tg-AD and non-Tg offspring were carried out. We analyzed the gene expression of astrogliosis markers, the main components of the ECS and Ca2+ signaling. 3×Tg-AD hippocampal astrocytes show low inflammatory activity (Il1b, Il6, and Gls) and Ca2+ flow (P2rx5 and Mcu), associated with low cannabinoid signaling (Cnr1 and Cnr2). These results were more evident in females. Our study corroborates glial involvement in AD pathology, in which cannabinoid signaling plays an important role. 3×Tg-AD mice born with hippocampal astrocytes with differential gene expression of the ECS associated with an innate attenuation of their activity. In addition, we show that there are sex differences from birth in this AD animal, which should be considered when investigating the pathogenesis of the disease.
SsCak1 Regulates Growth and Pathogenicity in Sclerotinia sclerotiorum
Authors: Qin Lei , Nong Jieying , Cui Kan , Tang Xianyu , Gong Xin , Xia Yunong , Xu Yan , Qiu Yilan , Li Xin , Xia Shitou
Published: August 2023

Sclerotinia sclerotiorum is a devastating fungal pathogen that causes severe crop losses worldwide. It is of vital importance to understand its pathogenic mechanism for disease control. Through a forward genetic screen combined with next-generation sequencing, a putative protein kinase, SsCak1, was found to be involved in the growth and pathogenicity of S. sclerotiorum. Knockout and complementation experiments confirmed that deletions in SsCak1 caused defects in mycelium and sclerotia development, as well as appressoria formation and host penetration, leading to complete loss of virulence. These findings suggest that SsCak1 is essential for the growth, development, and pathogenicity of S. sclerotiorum. Therefore, SsCak1 could serve as a potential target for the control of S. sclerotiorum infection through host-induced gene silencing (HIGS), which could increase crop resistance to the pathogen.
In Silico Discovery of Potential Inhibitors Targeting the RNA Binding Loop of ADAR2 and 5-HT2CR from Traditional Chinese Natural Compounds
Authors: Broni Emmanuel , Ashley Carolyn , Velazquez Miriam , Khan Sufia , Striegel Andrew , Sakyi Patrick O. , Peracha Saqib , Bebla Kristeen , Sodhi Monsheel , Kwofie Samuel K. , Ademokunwa Adesanya , Miller Whelton A.
Published: August 2023

Adenosine deaminase acting on RNA 2 (ADAR2) is an important enzyme involved in RNA editing processes, particularly in the conversion of adenosine to inosine in RNA molecules. Dysregulation of ADAR2 activity has been implicated in various diseases, including neurological disorders (including schizophrenia), inflammatory disorders, viral infections, and cancers. Therefore, targeting ADAR2 with small molecules presents a promising therapeutic strategy for modulating RNA editing and potentially treating associated pathologies. However, there are limited compounds that effectively inhibit ADAR2 reactions. This study therefore employed computational approaches to virtually screen natural compounds from the traditional Chinese medicine (TCM) library. The shortlisted compounds demonstrated a stronger binding affinity to the ADAR2 (<−9.5 kcal/mol) than the known inhibitor, 8-azanebularine (−6.8 kcal/mol). The topmost compounds were also observed to possess high binding affinity towards 5-HT2CR with binding energies ranging from −7.8 to −12.9 kcal/mol. Further subjecting the top ADAR2–ligand complexes to molecular dynamics simulations and molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) calculations revealed that five potential hit compounds comprising ZINC000014637370, ZINC000085593577, ZINC000042890265, ZINC000039183320, and ZINC000101100339 had favorable binding free energies of −174.911, −137.369, −117.236, −67.023, and −64.913 kJ/mol, respectively, with the human ADAR2 protein. Residues Lys350, Cys377, Glu396, Cys451, Arg455, Ser486, Gln488, and Arg510 were also predicted to be crucial in ligand recognition and binding. This finding will provide valuable insights into the molecular interactions between ADAR2 and small molecules, aiding in the design of future ADAR2 inhibitors with potential therapeutic applications. The potential lead compounds were also profiled to have insignificant toxicities. A structural similarity search via DrugBank revealed that ZINC000039183320 and ZINC000014637370 were similar to naringin and naringenin, which are known adenosine deaminase (ADA) inhibitors. These potential novel ADAR2 inhibitors identified herein may be beneficial in treating several neurological disorders, cancers, viral infections, and inflammatory disorders caused by ADAR2 after experimental validation.
Shedding Light on the Photophysics and Photochemistry of I-Motifs Using Quantum Mechanical Calculations
Authors: Improta Roberto
Published: August 2023

I-motifs are non-canonical DNA structures formed by intercalated hemiprotonated (CH·C)+ pairs, i.e., formed by a cytosine (C) and a protonated cytosine (CH+), which are currently drawing great attention due to their biological relevance and promising nanotechnological properties. It is important to characterize the processes occurring in I-motifs following irradiation by UV light because they can lead to harmful consequences for genetic code and because optical spectroscopies are the most-used tools to characterize I-motifs. By using time-dependent DFT calculations, we here provide the first comprehensive picture of the photoactivated behavior of the (CH·C)+ core of I-motifs, from absorption to emission, while also considering the possible photochemical reactions. We reproduce and assign their spectral signatures, i.e., infrared, absorption, fluorescence and circular dichroism spectra, disentangling the underlying chemical–physical effects. We show that the main photophysical paths involve C and CH+ bases on adjacent steps and, using this basis, interpret the available time-resolved spectra. We propose that a photodimerization reaction can occur on an excited state with strong C→CH+ charge transfer character and examine some of the possible photoproducts. Based on the results reported, some future perspectives for the study of I-motifs are discussed.
A Novel Transgenic Mouse Model Implicates Sirt2 as a Promoter of Hepatocellular Carcinoma
Authors: Schmidt Alexandra V. , Monga Satdarshan P. , Prochownik Edward V. , Goetzman Eric S.
Published: August 2023

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths globally. Incidence rates are steadily increasing, creating an unmet need for new therapeutic options. Recently, the inhibition of sirtuin-2 (Sirt2) was proposed as a potential treatment for HCC, despite contradictory findings of its role as both a tumor promoter and suppressor in vitro. Sirt2 functions as a lysine deacetylase enzyme. However, little is known about its biological influence, despite its implication in several age-related diseases. This study evaluated Sirt2’s role in HCC in vivo using an inducible c-MYC transgene in Sirt2+/+ and Sirt2−/− mice. Sirt2−/− HCC mice had smaller, less proliferative, and more differentiated liver tumors, suggesting that Sirt2 functions as a tumor promoter in this context. Furthermore, Sirt2−/− HCCs had significantly less c-MYC oncoprotein and reduction in c-MYC nuclear localization. The RNA-seq showed that only three genes were significantly dysregulated due to loss of Sirt2, suggesting the underlying mechanism is due to Sirt2-mediated changes in the acetylome, and that the therapeutic inhibition of Sirt2 would not perturb the oncogenic transcriptome. The findings of this study suggest that Sirt2 inhibition could be a promising molecular target for slowing HCC growth.
Simple Knowledge Graph Completion Model Based on Differential Negative Sampling and Prompt Learning
Authors: Duan Li , Wang Jing , Luo Bing , Sun Qiao
Published: August 2023

Knowledge graphs (KGs) serve as a crucial resource for numerous artificial intelligence tasks, significantly contributing to the advancement of the AI field. However, the incompleteness of existing KGs hinders their effectiveness in practical applications. Consequently, researchers have proposed the task of KG completion. Currently, embedding-based techniques dominate the field as they leverage the structural information within KGs to infer and complete missing parts. Nonetheless, these methods exhibit limitations. They are limited by the quality and quantity of structural information and are unable to handle the missing entities in the original KG. To overcome these challenges, researchers have attempted to integrate pretrained language models and textual data to perform KG completion. This approach utilizes the definition statements and description text of entities within KGs. The goal is to compensate for the latent connections that are difficult for traditional methods to obtain. However, text-based methods still lag behind embedding-based models in terms of performance. Our analysis reveals that the critical issue lies in the selection process of negative samples. In order to enhance the performance of the text-based methods, various types of negative sampling methods are employed in this study. We introduced prompt learning to fill the gap between the pre-training language model and the knowledge graph completion task, and to improve the model reasoning level. Simultaneously, a ranking strategy based on KG structural information is proposed to utilize KG structured data to assist reasoning. The experiment results demonstrate that our model exhibits strong competitiveness and outstanding inference speed. By fully exploiting the internal structural information of KGs and external relevant descriptive text resources, we successfully elevate the performance levels of KG completion tasks across various metrics.
Surgery for Infective Endocarditis after Primary Transcatheter Aortic-Valve Replacement—A Retrospective Single-Center Analysis
Authors: Rösch Romina Maria , Brendel Lena , Buschmann Katja , Vahl Christian-Friedrich , Treede Hendrik , Dohle Daniel-Sebastian
Published: August 2023

Transcatheter aortic-valve replacement (TAVR) is increasingly being used for the treatment of aortic-valve stenosis. Therefore, the total number of patients with an aortic-valve prosthesis is increasing, causing the incidence of prosthetic-valve endocarditis to increase. Methods: Between March 2016 and July 2019, ten patients underwent surgery due to prosthetic-valve endocarditis after TAVR. They were identified in our institutional database and analyzed. Results: Infective endocarditis was diagnosed 17 ± 16 month after TAVR. Mean age was 79 ± 4.4 years. Microbiological detection showed 6/10 positive blood cultures for enterococcus faecalis. Median EuroScore II was 24.64%. The mean size of the surgically replaced aortic prosthesis was 23.6 ± 1.3 and that of the TAVR was 28.4 ± 2.3 mm. The surgically implanted aortic valves had a mean gradient of 8.5 ± 2.2 mmHg. One patient died in hospital due to septic multiorgan failure. After discharge, all patients survived with a mean follow-up of 9 ± 8 month. Conclusions: With a rising number of patients after TAVR, prosthetic-valve endocarditis will increasingly occur in patients who were previously considered high or intermediate risk. Our results show that patients with TAVR infective endocarditis can be operated on with good results. Surgical therapy should not be withheld from TAVR patients with infective endocarditis.
Current Knowledge on the Different Characteristics of Back Pain in Adults with and without Scoliosis: A Systematic Review
Authors: Zaina Fabio , Marchese Rosemary , Donzelli Sabrina , Cordani Claudio , Pulici Carmelo , McAviney Jeb , Negrini Stefano
Published: August 2023

Patients with scoliosis have a high prevalence of back pain (BP). It is possible that scoliosis patients present with specific features when experiencing back or leg pain pathology. The aim of this systematic review is to report the signs, symptoms and associated features of BP in patients with scoliosis compared to adults without scoliosis during adulthood. From inception to 15 May 2023, we searched the following databases: PubMed, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus. We found 10,452 titles, selected 25 papers for full-text evaluation and included 8 in the study. We found that scoliosis presents with asymmetrical pain, most often at the curve’s apex, eventually radiating to one leg. Radiating symptoms are usually localised on the front side of the thigh (cruralgia) in scoliosis, while sciatica is more frequent in non-scoliosis subjects. These radiating symptoms relate to rotational olisthesis. The type and localization of the curve have an impact, with lumbar and thoracolumbar curves being more painful than thoracic. Pain in adults with scoliosis presents specific features: asymmetrical localization and cruralgia. These were the most specific features. It remains unclear whether pain intensity and duration can differentiate scoliosis and non-scoliosis-related pain in adults.
A New Test for Achilles Tendinopathy Based on Kager’s Fat Pad Clinical Assessment Predictive Values
Authors: Rodríguez-Sanz David , Losa-Iglesias Marta Elena , de Bengoa-Vallejo Ricardo Becerro , Sánchez-Milá Zacarías , Dorgham Hend Adel Abdelhalim , Elerian Ahmed Ebrahim , Yu Tian , Calvo-Lobo César , Velázquez-Saornil Jorge , Martínez Jimene Eva María
Published: August 2023

Background This study aimed to check the diagnostic accuracy of a new test to identify Achilles tendinopathy. Study Design: Observational study. Methods: Seventy patients recruited from a private medical centre met the diagnostic criteria for unilateral Achilles tendinopathy (age, 45.1 ± 12.7 years; weight, 75.00 ± 10 kg; height, 1.75 ± 0.1 m) and were tested based on both Achilles tendons. Seventy patients with a unilateral Achilles tendinopathy ultrasound diagnosis were tested using David’s test. Results: Most (86%) subjects demonstrated Kager’s fat pad asymmetry in relation to the Achilles tendon in the complete passive dorsiflexion in the prone position (David’s sign). No healthy tendons had David’s sign. Conclusions: The presence of asymmetry in Kager’s fat pad in relation to the Achilles tendon during complete passive dorsiflexion is strongly indicative of ultrasound-diagnosed tendinopathy. David’s test demonstrated a sensitivity of 85.71% (95% CI, 77.51% to 93.91%) and a specificity of 100% (95% CI, 100% to 100%), while noting the lack of blinding of the assessors and the uncertainty of the diagnostic measures (95% CI). Asymmetry of the fat pad could potentially serve as a characteristic marker for patients with Achilles tendinopathy.
Effects of Etanercept and Adalimumab on Serum Levels of Cartilage Remodeling Markers in Women with Rheumatoid Arthritis
Authors: Szeremeta Anna , Jura-Półtorak Agnieszka , Zoń-Giebel Aleksandra , Olczyk Krystyna , Komosińska-Vassev Katarzyna
Published: August 2023

Tumor necrosis factor α inhibitor (TNFαI) therapy is associated with a significant inhibition of radiographic progression, resulting in improved physical function and quality of life among patients with rheumatoid arthritis (RA). The mechanism by which TNFαI prevent joint destruction is still unknown. In this study, the effect of 15-month anti-TNF-α therapy in combination with methotrexate on circulating levels of biochemical markers of cartilage turnover in female RA patients was assessed. Serum levels of collagen type II C-terminal cleavage neoepitope (C2C), C-terminal propeptide of type II collagen (PIICP), cartilage oligomeric matrix protein (COMP), and matrix metalloproteinase-3 (MMP-3) were evaluated using immunoassays at baseline and 15 months after the start of TNFαI treatment. Baseline COMP, C2C, and MMP-3 levels and C2C/PIICP ratios were significantly higher in women with RA compared with those observed in the healthy subjects. No differences in PIICP levels between the controls and the women with RA were observed. After 15 months of TNFαI treatment, serum levels of C2C, COMP, and MMP-3 decreased, whereas the levels of PIICP increased but were still not different from those of the controls. These changes were accompanied by significantly reduced C2C/PIICP ratios. Before the start of TNFαI therapy, serum levels of COMP significantly correlated with the patients’ ages (p < 0.05) and their 28-joint disease activity score values based on their erythrocyte sedimentation rates (DAS28-ESR; p < 0.05). Moreover, multiple linear regression analysis showed that baseline COMP levels retained a significant association with DAS28-ESR value (β = 287.74, p = 0.022, R2 model = 0.25) after model adjustments. The largest area under the ROC curve was obtained for C2C/PIICP ratios (AUC: 0.830, 95% CI: 0.727–0.932, p < 0.001). Our results suggest that long-term anti-TNF-α therapy combined with MTX has a beneficial effect on cartilage remodeling that is associated with clinical improvement among RA patients. Serum C2C/PIICP ratios may help to monitor the effectiveness of anti-TNF-α treatment among RA patients.
Diaphragm Dysfunction and ICU-Acquired Weakness in Septic Shock Patients with or without Mechanical Ventilation: A Pilot Prospective Observational Study
Authors: Takahashi Yuta , Morisawa Tomoyuki , Okamoto Hiroshi , Nakanishi Nobuto , Matsumoto Noriko , Saitoh Masakazu , Takahashi Tetsuya , Fujiwara Toshiyuki
Published: August 2023

Sepsis is a risk factor for diaphragm dysfunction and ICU-acquired weakness (ICU-AW); however, the impact of mechanical ventilation (MV) on these relationships has not been thoroughly investigated. This study aimed to compare the incidence of diaphragm dysfunction and ICU-AW in patients with septic shock, with and without MV. We conducted a single-center prospective observational study that included consecutive patients diagnosed with septic shock admitted to the ICU between March 2021 and February 2022. Ultrasound measurements of diaphragm thickness and manual measurements of limb muscle strength were repeated after ICU admission. The incidences of diaphragm dysfunction and ICU-AW, as well as their associations with clinical outcomes, were compared between patients with MV and without MV (non-MV). Twenty-four patients (11 in the MV group and 13 in the non-MV group) were analyzed. At the final measurements in the MV group, eight patients (72.7%) had diaphragm dysfunction, and six patients (54.5%) had ICU-AW. In the non-MV group, 10 patients (76.9%) had diaphragm dysfunction, and three (23.1%) had ICU-AW. No association was found between diaphragm dysfunction and clinical outcomes. Patients with ICU-AW in the MV group had longer ICU and hospital stays. Among patients with septic shock, the incidence of diaphragm dysfunction was higher than that of ICU-AW, irrespective of the use of MV. Further studies are warranted to examine the association between diaphragm dysfunction and clinical outcomes.
Long-Term Outcomes of Extracorporeal Life Support in Respiratory Failure
Authors: Burša Filip , Frelich Michal , Sklienka Peter , Jor Ondřej , Máca Jan
Published: August 2023

Although extracorporeal life support is an expensive method with serious risks of complications, it is nowadays a well-established and generally accepted method of organ support. In patients with severe respiratory failure, when conventional mechanical ventilation cannot ensure adequate blood gas exchange, veno-venous extracorporeal membrane oxygenation (ECMO) is the method of choice. An improvement in oxygenation or normalization of acid–base balance by itself does not necessarily mean an improvement in the outcome but allows us to prevent potential negative effects of mechanical ventilation, which can be considered a crucial part of complex care leading potentially to an improvement in the outcome. The disconnection from ECMO or discharge from the intensive care unit should not be viewed as the main goal, and the long-term outcome of the ECMO-surviving patients should also be considered. Approximately three-quarters of patients survive the veno-venous ECMO, but various (both physical and psychological) health problems may persist. Despite these, a large proportion of these patients are eventually able to return to everyday life with relatively little limitation of respiratory function. In this review, we summarize the available knowledge on long-term mortality and quality of life of ECMO patients with respiratory failure.
Liver dECM–Gelatin Composite Bioink for Precise 3D Printing of Highly Functional Liver Tissues
Authors: Kim Min Kyeong , Jeong Wonwoo , Kang Hyun-Wook
Published: August 2023

In recent studies, liver decellularized extracellular matrix (dECM)-based bioinks have gained significant attention for their excellent compatibility with hepatocytes. However, their low printability limits the fabrication of highly functional liver tissue. In this study, a new liver dECM–gelatin composite bioink (dECM gBioink) was developed to overcome this limitation. The dECM gBioink was prepared by incorporating a viscous gelatin mixture into the liver dECM material. The novel dECM gBioink showed 2.44 and 10.71 times higher bioprinting resolution and compressive modulus, respectively, than a traditional dECM bioink. In addition, the new bioink enabled stable stacking with 20 or more layers, whereas a structure printed with the traditional dECM bioink collapsed. Moreover, the proposed dECM gBioink exhibited excellent hepatocyte and endothelial cell compatibility. At last, the liver lobule mimetic structure was successfully fabricated with a precisely patterned endothelial cell cord-like pattern and primary hepatocytes using the dECM gBioink. The fabricated lobule structure exhibited excellent hepatic functionalities and dose-dependent responses to hepatotoxic drugs. These results demonstrated that the gelatin mixture can significantly improve the printability and mechanical properties of the liver dECM materials while maintaining good cytocompatibility. This novel liver dECM gBioink with enhanced 3D printability and resolution can be used as an advanced tool for engineering highly functional liver tissues.
Copy Number Variations and Gene Mutations Identified by Multiplex Ligation-Dependent Probe Amplification in Romanian Chronic Lymphocytic Leukemia Patients
Authors: Balla Beata , Tripon Florin , Candea Marcela , Banescu Claudia
Published: August 2023

Chronic lymphocytic leukemia (CLL) is known for its wide-ranging clinical and genetic diversity. The study aimed to assess the associations between copy number variations (CNVs) and various biological and clinical features, as well as the survival rates of CLL patients and to evaluate the effectiveness of the multiplex ligation-dependent probe amplification (MLPA) technique in CLL patients.DNA was extracted from 110 patients, and MLPA was performed. Mutations in NOTCH1, SF3B1, and MYD88 were also analyzed. A total of 52 patients showed at least one CNV, 26 had at least one somatic mutation, and 10 presented both, CNVs, and somatic mutations. The most commonly identified CNVs were del(114.3), del(11q22.3), and dup(12q23.2). Other CNVs identified included del(17p13.1), del(14q32.33), dup(10q23.31), and del(19p13.2). One patient was identified with concomitant trisomy 12, 13, and 19. NOTCH1 and SF3B1 mutations were found in 13 patients each, either alone or in combination with other mutations or CNVs, while MYD88 mutation was identified in one patient. Forty-two patients had normal results. Associations between the investigated CNVs and gene mutations and patients’ overall survival were found. The presence of NOTCH1 and SF3B1 mutations or the combination of NOTCH1 mutation and CNVs significantly influenced the survival of patients with CLL. Both mutations are frequently associated with different CNVs. Del(13q) is associated with the longest survival rate, while the shortest survival is found in patients with del(17p). Even if MLPA has constraints, it may be used as the primary routine analysis in patients with CLL.
A Transition to Multimodal Multilingual Practice: From SimCom to Translanguaging
Authors: Silvestri Julia , Falk Jodi L.
Published: August 2023

Historically, the field of deaf education has revolved around language planning discourse, but little research has been conducted on Deaf and Hard of Hearing (DHH) students with additional disabilities as dynamic multilingual and multimodal language users. The current study focuses on the language planning process at a school serving DHH and Deaf–Blind students with varied additional disabilities. A previous Total Communication philosophy at the school was implemented in practice as Simultaneous Communication (SimCom) and later revised as a multimodal-multilingual approach with the goal of separating American Sign Language (ASL) and English and using multimodal communication such as tactile ASL and Augmentative and Alternative Communication (AAC). To implement this philosophy without reverting back to SimCom, the school employed a language planning process using action research to reflect on cycles of improvement. A grounded theory approach was used to identify and analyze themes over a three-year period of language planning and professional development in multimodal communication. Triangulated data includes language planning artifacts and an online survey of staff perceptions—analyzed by coding concepts and categories, relating concepts to define translanguaging mechanisms and attitudes, and developing an overarching theory on how a school values translanguaging after 3 years of valuing complete access to language. In the context of a multilingual, multimodal language planning cycle, developing a shared language ideology guided by how Deaf, DeafBlind, and Deaf-Disabled (DDBDD) people use language emerged as an overarching theme that promoted dynamic languaging and understanding of strategies for effective communication.
First Fossil Record of Trichomanes sensu lato (Hymenophyllaceae) from the Mid-Cretaceous Kachin Amber, Myanmar
Authors: Li Ya , Ebihara Atsushi , Nosova Natalya , Tan Zhen-Zhen , Cui Yi-Ming
Published: August 2023

Hymenophyllaceae (filmy ferns), with ca. 430 species, are the most species-rich family of early diverging leptosporangiate ferns but have a poor fossil record dating back to the Late Triassic period. Traditionally, Hymenophyllaceae comprise two species-rich genera or clades: Hymenophyllum (hymenophylloids) and Trichomanes sensu lato (s.l.) (trichomanoids). Unequivocal fossils of Hymenophyllum have been reported from the Early Cretaceous of central Mongolia and the early Eocene of Okanogan Highlands, Washington, USA. However, despite being a highly diversified lineage with an estimated 184 extant species, Trichomanes s.l. lack a definitive fossil record, which severely affects the reliability of the molecular dating of this group. Here, we report the first unequivocal fossil record of Trichomanes s.l. as T. angustum comb. nov. on the basis of fertile material with tubular involucres and long exserted receptacles from the mid-Cretaceous Kachin amber, Myanmar. This species was previously tentatively assigned to Hymenophyllites due to a lack of fertile evidence. Inferred to be an epiphytic fern, T. angustum further enriches the species diversity of the epiphytic palaeocommunities in the mid-Cretaceous Kachin amber, which are mainly composed of Porellalean leafy liverworts and Dicranalean and Hypnodendralean mosses. Fossil records indicate that Hymenophyllaceae probably originated in the tropical Pangea at the latest in the Triassic when all continents were coalesced into a single landmass and had already accumulated some notable diversity in low-middle latitude areas of Laurasia by the mid-Cretaceous period.
Pressure Ulcer Diagnosis Is Associated with Increased Mortality in Patients with End-Stage Renal Disease: A Retrospective Study
Authors: Duchesne Gabriela A. , Waller Jennifer L. , Baer Stephanie L. , Young Lufei , Bollag Wendy B.
Published: August 2023

Pressure ulcers are associated with multiple comorbidities and annually affect approximately 3 million Americans, directly accounting for approximately 60,000 deaths per year. Because patients with end-stage renal disease (ESRD) are known to present with unique factors which impair wound healing, pressure ulcers diagnosed in ESRD patients might independently increase the risk of mortality. To investigate the association between pressure ulcer diagnosis and mortality risk in the ESRD population, a retrospective analysis of the United States Renal Data System (USRDS) database was performed. The records of 1,526,366 dialysis patients who began therapy between 1 January 2005 and 31 December 2018 were included. Our analysis showed that the diagnosis of pressure ulcers in this population was independently associated with mortality even after controlling for confounding factors (p < 0.001). A Kaplan–Meier survival analysis demonstrated reduced survival in patients with a pressure ulcer diagnosis compared to those without a pressure ulcer diagnosis. These results establish pressure ulcers as a significant independent risk factor for mortality, as well as suggesting several comorbidities as potential risk factors for pressure ulcers in the ESRD population.
Experimental Investigation and Modeling of Film Flow Corrosion
Authors: Ilie Marius Ciprian , Maior Ioana , Raducanu Cristian Eugen , Deleanu Iuliana Mihaela , Dobre Tanase , Parvulescu Oana Cristina
Published: August 2023

The paper focuses on the experimental investigation and mathematical modeling of the corrosion of steel when a film of water flows over its surface. The experimental monitoring of corrosion dynamics in the flowing film was carried out using a laboratory pilot model, exploited in such a way as to obtain data necessary to identify some characteristic parameters of the mathematical model of this problem. The mathematical model of the case takes into account the transfer of oxygen through the liquid film flowing on the surface of the corroding plate where the chemical surface processes characteristic of corrosion occur (dissolution of Fe, oxidation of Fe2+ to Fe3+, formation of surface deposit, etc.). Experimental measurements were used to identify the parameters of the mathematical model, especially the reaction constant of the Fe dissolution rate and the surface oxidation yield of Fe2+ to Fe3+. Calculation of the correlation coefficients for the apparent constant surface reaction rate and process factors showed that they correlate strongly and non-linearly with the Reynolds number (Re) of the film flow, with the cumulative flow duration, and with the cumulative standby time of the experiments. Using the dynamics of the resistance to the transfer of oxygen through the rust film and the dynamics of its thickness resulting from the specific flow of rust deposition, the apparent oxygen diffusion coefficient through the rust film formed on the plate was expressed.
Microstructure and Wear Resistance of Laser-Treated and Slow Cooled AlSi10Mg-(x)Ni Alloys
Authors: Moura Danusa , Gouveia Guilherme , Spinelli José
Published: August 2023

This study examined the solidification features and wear of AlSi10Mg(-Ni) alloy samples generated under various conditions. Additions were varied from 0 to 3 wt% Ni while maintaining Si and Mg contents. All samples were directionally solidified (DS) and laser treated using surface laser remelting (LSR). Both DS and LSR samples were characterized by a number of methods, including the following: thermal analysis, optical microscopy, stereomicroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), wear tests, and Vickers hardness. Ranges for cooling rates, dendritic spacing and hardness, respectively, were from 0.4 to 13.3 K/s, from 77 to 388 μm, from 71 to 93 HV for the DS samples and from 4.3 × 104 to 8.7 × 104 K/s, from 1.0 to 2.0 μm, and from 114 to 143 HV for the LSR (100 J/mm2). The solidification kinetics had a large impact on the solidified samples, allowing a representative range of microstructures and morphologies to be examined in terms of wear. The 1% Ni alloy had the highest wear resistance among all the DS samples under slow cooling and the short-term wear test (10 min/0.5 N), while the LSR samples showed similar wear resistances regardless of the Ni content. The uniform dispersions of Si and Al3Ni forming intercellular dense walls at the top of the laser molten pool together with their rod-like morphologies and reduced dendrite spacing of less than 2 μm, improved bonding with the matrix, resulting in higher and more consistent wear resistance of the laser treated surfaces.
Baicalin Attenuated PANX-1/P2X7 Axis, P2Y6, and NLRP3/Caspase-1 Signaling Pathways in Peritonitis Induced by Glaesserella parasuis
Authors: Fu Shulin , Tian Xinyue , Li Jingyang , Yuan Yuzhen , Li Xiaoyi , Ren Mingxing , Guo Ling , Ye Chun , Zong Bingbing , Liu Yu , Lu Qirong , Qiu Yinsheng
Published: August 2023

Glaesserella parasuis (G. parasuis) can cause peritonitis in piglets. However, the pathogenesis of peritonitis remains unclear. Baicalin has been shown to possess anti-inflammatory and anti-oxidant functions. The aim of this study was to investigate the role of the PANX-1/P2X7 axis and the P2Y6 signaling pathway in peritonitis induced by G. parasuis and the effect of baicain on the PANX-1/P2X7 axis and P2Y6 pathway activation triggered by G. parasuis. A G. parasuis serovar 5 isolate SH0165 strain was obtained from the lungs of commercially produced pigs which had the typical symptoms of Glässer’s disease, namely arthritis, fibrinous polyserositis, hemorrhagic pneumonia, and meningitis. Then, 35 piglets were randomly divided into five groups, each group containing seven piglets. The groups consisted of a negative control group, an infection group, a 25 mg/kg baicalin group, a 50 mg/kg baicalin group, and a 100 mg/kg baicalin group. The results showed that G. parasuis could promote PANX-1/P2X7 axis and P2Y6 activation; induce NLRP3/caspase-1, IL-1β and IL-18 expression; trigger PLC/PKC and MLCK/MLC signaling activation; attenuate the expression of tight junction proteins ZO-1, E-cadherin, Occludins, and claudin 1; and stimulate CD14, CD24, CD36, CD47, and CD91 expression in the peritoneum as measured via Western blot (p < 0.01; PLC, p < 0.05). Baicalin could significantly inhibit PANX-1/P2X7 axis, P2Y6, and NLRP3/caspase-1 activation; reduce IL-1β and IL-18 expression; attenuate PLC/PKC and MLCK/MLC activation; promote ZO-1, E-cadherin, occludins, and claudin 1 expression; and reduce CD14, CD24, CD36, CD47, and CD91 expression in the peritoneum induced by G. parasuis as measured via Western blot. Our results deepen the understanding of the mechanism of peritonitis triggered by G. parasuis and provide some novel potential methods of controlling G. parasuis infection.
Mineralogy of Agates with Amethyst from the Tevinskoye Deposit (Northern Kamchatka, Russia)
Authors: Svetova Evgeniya N. , Palyanova Galina A. , Borovikov Andrey A. , Posokhov Viktor F. , Moroz Tatyana N.
Published: August 2023

The Tevinskoye agate deposit is located in the North of the Kamchatka peninsula (Russia) and represented by agate-bearing Eocene basaltic and andesitic rocks of the Kinkilsk complex. Agate mineralization occurs in lavas and tuffs as amygdales, geodes, lenses and veins, which are the main sources of the resupply of coastal agate placers. The present study aimed to perform a comprehensive mineralogical, geochemical, and O-isotope investigation of amethyst-bearing agates, and to evaluate data concerning the origin of mineralization and the conditions for amethyst formation. Agates exhibit spectacular textures, with variation in the sequence of silica filling of amygdales and geodes. The mineral composition of the agates is mainly represented by micro- and macro-crystalline quartz, amethyst, length-fast and zebraic chalcedony, moganite, goethite, and clinoptilolite. Carbonate forms individual bands in the outer zones of some agates. The presence of small amounts of native copper, covellite, chalcopyrite and pyrite is a feature of these agates. Copper and iron mineralization are probably typomorphic features related to the host rock composition. The measured values of crystallite size (525–560 Å) and the high moganite content (up to 50%) of agate with amethyst are evidenced by the young age (~45 Ma) of agate-hosting rocks. Agate formation temperatures (21–229 °C) were calculated from the O-isotope composition of chalcedony (+19.6 to +25.5‰), quartz (+18.1 to +22.3‰), and amethyst (+18.2 to +21.5‰). The cold-water monophase fluid inclusions revealed in amethyst crystals suggest that the mineralizing fluids have low temperatures (<100 °C) and low salinity. Magnetite grains in host rock, together with goethite inclusions identified within the amethyst crystals, point to a change in redox conditions and the presence of iron in the agate-forming fluids, which entered the quartz lattice during crystallization and influenced the formation of the violet color.
Dissipation, Processing Factors and Dietary Exposure Assessment of Myclobutanil in Tomato
Authors: Qi Yanli , Cao Junli , Li Chunyong , Ren Pengcheng , Qin Shu , Li Jindong
Published: August 2023

Myclobutanil residue poses a potential threat to consumers’ health. This work aims to investigate the degradation behavior, residue levels, processing factors (PFs) and dietary risk of myclobutanil in tomato. Myclobutanil was analyzed using a modified quick, easy, cheap, effective, rugged, safe (QuEChERS) method combined with ultra-performance liquid chromatography–mass spectrometry (UPLC-MS/MS), and average recoveries ranged from 82% to 102% with relative standard deviations RSDs ≤ 9.1%. After spraying myclobutanil miscible oil under field conditions, the initial concentration of myclobutanil was 0.055 mg/kg, and its dissipation followed the first-order kinetics equation with a half-life of 2.88 days. Myclobutanil was mainly present in the tomato skin, and its concentration was about four times that in the whole tomato. The initial concentration of myclobutanil in raw tomato was 0.100 mg/kg. After washing, peeling, homogenization, simmering and canning, the residual level of myclobutanil decreased to 0.067 mg/kg, 0.023 mg/kg, 0.013 mg/kg, 0.044 mg/kg and 0.041 mg/kg, respectively. Although the procedure of simmering led to an increase in myclobutanil concentration, the PFs were all less than 1 in the whole process, showing that the processing procedure significantly decreased the residual level of myclobutanil canned tomato paste in comparison with the raw agricultural commodity. Washing, peeling, and homogenization played critical roles in reducing pesticide residues. The residues of myclobutanil during the processing of tomato pose low dietary exposure risks to consumers in China, which were acceptable. However, the acute and chronic risk quotient for children revealed that it was necessary to monitor the dietary exposure of pesticide residues for children closely.
Molecular and Cellular Mechanisms of Action of Cannabidiol
Authors: Martinez Naya Nadia , Kelly Jazmin , Corna Giuliana , Golino Michele , Abbate Antonio , Toldo Stefano
Published: August 2023

Cannabidiol (CBD) is the primary non-psychoactive chemical from Cannabis Sativa, a plant used for centuries for both recreational and medicinal purposes. CBD lacks the psychotropic effects of Δ9-tetrahydrocannabinol (Δ9-THC) and has shown great therapeutic potential. CBD exerts a wide spectrum of effects at a molecular, cellular, and organ level, affecting inflammation, oxidative damage, cell survival, pain, vasodilation, and excitability, among others, modifying many physiological and pathophysiological processes. There is evidence that CBD may be effective in treating several human disorders, like anxiety, chronic pain, psychiatric pathologies, cardiovascular diseases, and even cancer. Multiple cellular and pre-clinical studies using animal models of disease and several human trials have shown that CBD has an overall safe profile. In this review article, we summarize the pharmacokinetics data, the putative mechanisms of action of CBD, and the physiological effects reported in pre-clinical studies to give a comprehensive list of the findings and major effects attributed to this compound.
Synthesis and NO2 Sensing Properties of In2O3 Micro-Flowers Composed of Nanorods
Authors: Wang Zhenyu , Ding Haizhen , Liu Xuefeng , Zhao Jing
Published: August 2023

Semiconductor oxide gas sensors have important applications in environmental protection, domestic health, and other fields. Research has shown that designing the morphology of sensitive materials can effectively improve the sensing characteristics of sensors. In this paper, by controlling the solvothermal reaction time, a unique hexagonal flower-like structure of In2O3 materials consisting of cuboid nanorods with a side length of 100–300 nm was prepared. The characterization results indicated that with the increase in reaction time, the materials exhibited significant morphological evolution. When the solvent heating time is 5 h, the flower-like structure is basically composed of hexagonal nanosheets with a thickness of several hundred nanometers and a side length of several micrometers. With the increase in reaction time, the apex angles of the nano sheets gradually become obtuse, and, finally, with the Ostwald ripening process, they become cuboid nanorods with side lengths of 100–300 nanometers, forming unique micro-flowers. Among them, the material prepared with a reaction time of 20 h has good sensing performance for NO2, exhibiting low operating temperature and detection limit, good selectivity, repeatability, and long-term stability, thus suggesting a good application prospect.
Pillared Carbon Membranes Derived from Cardo Polymers
Authors: Tajik Masoumeh , Bin Haque Syed Fahad , Perez Edson V. , Vizuet Juan P. , Firouzi Hamid Reza , Balkus Kenneth J. , Musselman Inga H. , Ferraris John P.
Published: August 2023

Carbon molecular sieve membranes (CMSMs) were prepared by carbonizing the high free volume polyimide BTDA-BAF that is obtained from the reaction of benzophenone-3,3′,4,4′-tetracarboxylic dianhydride (BTDA) and 9,9-bis(4-aminophenyl) fluorene (BAF). The bulky cardo groups prevented a tight packing and rotation of the chains that leads to high permeabilities of their CMSMs. The incorporation of metal–organic polyhedra 18 (MOP-18, a copper-based MOP) in the BTDA-BAF polymer before pyrolysis at 550 °C prevented the collapse of the pores and the aging of the CMSMs. It was found that upon decomposition of MOP-18, a distribution of copper nanoparticles minimized the collapse of the graphitic sheets that formed the micropores and mesopores in the CMSM. The pillared CMSMs displayed CO2 and CH4 permeabilities of 12,729 and 659 Barrer, respectively, with a CO2/CH4 selectivity of 19.3 after 3 weeks of aging. The permselectivity properties of these membranes was determined to be at the 2019 Robeson upper bound. In contrast, the CMSMs from pure BTDA-BAF aged three times faster than the CMSMs from MOP-18/BTDA-BAF and exhibited lower CO2 and CH4 permeabilities of 5337 and 573 Barrer, respectively, with a CO2/CH4 selectivity of 9.3. The non-pillared CMSMs performed below the upper bound.