bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of the NF-κB Signaling Pathway Alleviates Pyroptosis in Bladder Epithelial Cells and Neurogenic Bladder Fibrosis
Authors: Chen Jing , Li Qi , Hong Yifan , Zhou Xiazhu , Yu Chengjun , Tian Xiaomao , Zhao Jie , Long Chunlan , Shen Lianju , Wu Shengde , Wei Guanghui
Published: July 2023

Most children with a neurogenic bladder (NB) have bladder fibrosis, which causes irreversible bladder dysfunction and damage to the upper urinary tract. However, the mechanism of bladder fibrosis remains unclear. This study aimed to investigate the underlying causes of bladder fibrosis. Here, the lumbar 6 (L6) and sacral 1 (S1) spinal nerves of Sprague Dawley rats were severed bilaterally to establish NB models. Using RNA-seq, we discovered that the NF-κB signaling pathway and inflammation were upregulated in spinal cord injury (SCI)-induced bladder fibrosis. Subsequent Western blotting, enzyme-linked immunosorbent assays, immunohistochemical staining, and immunofluorescence staining verified the RNA-seq findings. To further clarify whether the NF-κB signaling pathway and pyroptosis were involved in bladder fibrosis, a TGF-β1-treated urinary epithelial cell line (SV-HUC-1 cells) was used as an in vitro model. Based on the results of RNA-seq, we consistently found that the NF-κB signaling pathway and pyroptosis might play important roles in TGF-β1-treated cells. Further experiments also confirmed the RNA-seq findings in vitro. Moreover, using the NLRP3 inhibitor MCC950 rescued TGF-β1-induced fibrosis, and the NF-κB signaling pathway inhibitor BAY 11-7082 effectively rescued TGF-β1-induced pyroptosis and the deposition of extracellular matrix by SV-HUC-1 cells. In summary, our research demonstrated for the first time that the NF-κB signaling pathway inhibition rescued bladder epithelial cells pyroptosis and fibrosis in neurogenic bladders.
Extracellular Succinate: A Physiological Messenger and a Pathological Trigger
Authors: Wu Kenneth K.
Published: July 2023

When tissues are under physiological stresses, such as vigorous exercise and cold exposure, skeletal muscle cells secrete succinate into the extracellular space for adaptation and survival. By contrast, environmental toxins and injurious agents induce cellular secretion of succinate to damage tissues, trigger inflammation, and induce tissue fibrosis. Extracellular succinate induces cellular changes and tissue adaptation or damage by ligating cell surface succinate receptor-1 (SUCNR-1) and activating downstream signaling pathways and transcriptional programs. Since SUCNR-1 mediates not only pathological processes but also physiological functions, targeting it for drug development is hampered by incomplete knowledge about the characteristics of its physiological vs. pathological actions. This review summarizes the current status of extracellular succinate in health and disease and discusses the underlying mechanisms and therapeutic implications.
Impact of Truncated Oxidized Phosphatidylcholines on Phospholipase A2 Activity in Mono- and Polyunsaturated Biomimetic Vesicles
Authors: Yordanova Vesela , Hazarosova Rusina , Vitkova Victoria , Momchilova Albena , Robev Bozhil , Nikolova Biliana , Krastev Plamen , Nuss Philippe , Angelova Miglena I. , Staneva Galya
Published: July 2023

The interplay between inflammatory and redox processes is a ubiquitous and critical phenomenon in cell biology that involves numerous biological factors. Among them, secretory phospholipases A2 (sPLA2) that catalyze the hydrolysis of the sn-2 ester bond of phospholipids are key players. They can interact or be modulated by the presence of truncated oxidized phosphatidylcholines (OxPCs) produced under oxidative stress from phosphatidylcholine (PC) species. The present study examined this important, but rarely considered, sPLA2 modulation induced by the changes in biophysical properties of PC vesicles comprising various OxPC ratios in mono- or poly-unsaturated PCs. Being the most physiologically active OxPCs, 1-palmitoyl-2-(5′-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC) have been selected for our study. Using fluorescence spectroscopy methods, we compared the effect of OxPCs on the lipid order as well as sPLA2 activity in large unilamellar vesicles (LUVs) made of the heteroacid PC, either monounsaturated [1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)], or polyunsaturated [1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (PDPC)] at a physiological temperature. The effect of OxPCs on vesicle size was also assessed in both the mono- and polyunsaturated PC matrices. Results: OxPCs decrease the membrane lipid order of POPC and PDPC mixtures with PGPC inducing a much larger decrease in comparison with POVPC, indicative that the difference takes place at the glycerol level. Compared with POPC, PDPC was able to inhibit sPLA2 activity showing a protective effect of PDPC against enzyme hydrolysis. Furthermore, sPLA2 activity on its PC substrates was modulated by the OxPC membrane content. POVPC down-regulated sPLA2 activity, suggesting anti-inflammatory properties of this truncated oxidized lipid. Interestingly, PGPC had a dual and opposite effect, either inhibitory or enhancing on sPLA2 activity, depending on the protocol of lipid mixing. This difference may result from the chemical properties of the shortened sn-2-acyl chain residues (aldehyde group for POVPC, and carboxyl for PGPC), being, respectively, zwitterionic or anionic under hydration at physiological conditions.
Complete Chloroplast Genomes and Comparative Analyses of Three Paraphalaenopsis (Aeridinae, Orchidaceae) Species
Authors: Chen Jinliao , Wang Fei , Zhao Zhuang , Li Minghe , Liu Zhongjian , Peng Donghui
Published: July 2023

Paraphalaenopsis, a genus of perennial herbs from the family Orchidaceae, contains a number of ornamental species. However, there is no information on the chloroplast genomes of Paraphalaenopsis, which limits our studies of this genus. In this study, we reported the chloroplast genomes of three species of Paraphalaenopsis (P. labukensis, P. denevel, and P. laycockii ‘Semi-alba’) and performed comprehensive comparative analysis. These three chloroplast genomes showed a typical quadripartile structure. Their lengths ranged from 147,311 bp to 149,240 bp. Each genome contained 120 unique genes, including 74 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Comparative analysis revealed major differences in sequence divergence in the three chloroplast genomes. In addition, six hypervariable regions were identified (psbM-trnDGUC, psbB, ccsA, trnKUUU, trnSGCU-trnGUCC, rps16-trnQUUG) that can be used as DNA molecular markers. Phylogenetic relationships were determined using the chloroplast genomes of 28 species from 12 genera of Aeridinae. Results suggested that Paraphalaenopsis was a clade of Aeridinae that was sister to the Holcoglossum-Vanda clade, with 100% bootstrap support within Aeridinae. The findings of this study provided the foundation for future studies on the phylogenetic analysis of Aeridinae.
Involvement of the p38/MK2 Pathway in MCLR Hepatotoxicity Revealed through MAPK Pharmacological Inhibition and Phosphoproteomics in HepaRG Cells
Authors: Lynch Katherine D. , Iverson Dayne T. , Bachhav Namrata K. , Call Michael Ridge , Yue Guihua Eileen , Prasad Bhagwat , Clarke John D.
Published: July 2023

Microcystin-leucine arginine (MCLR) is one of the most common and toxic microcystin variants, a class of cyanotoxins produced by cyanobacteria. A major molecular mechanism for MCLR-elicited liver toxicity involves the dysregulation of protein phosphorylation through protein phosphatase (PP) inhibition and mitogen-activated protein kinase (MAPK) modulation. In this study, specific pharmacological MAPK inhibitors were used in HepaRG cells to examine the pathways associated with MCLR cytotoxicity. SB203580 (SB), a p38 inhibitor, rescued HepaRG cell viability, whereas treatment with SP600125 (JNK inhibitor), MK2206 (AKT inhibitor), or N-acetylcysteine (reactive oxygen species scavenger) did not. Phosphoproteomic analysis revealed that phosphosites—which were altered by the addition of SB compared to MCLR treatment alone—included proteins involved in RNA processing, cytoskeletal stability, DNA damage response, protein degradation, and cell death. A closer analysis of specific proteins in some of these pathways indicated that SB reversed the MCLR-mediated phosphorylation of the necroptosis-associated proteins, the mixed lineage kinase domain-like protein (MLKL), receptor-interacting serine/threonine kinase 1 (RIP1), DNA damage response proteins, ataxia telangiectasia and Rad3-related kinase (ATR), and checkpoint kinase 1 (CHK1). Overall, these data implicate p38/MK2, DNA damage, and necroptosis in MCLR-mediated hepatotoxicity, and suggest these pathways may be targets for prevention prior to, or treatment after, MCLR toxicity.
Advancing Cancer Research: Current Knowledge on Cutaneous Neoplasia
Authors: Stătescu Laura , Trandafir Laura Mihaela , Țarcă Elena , Moscalu Mihaela , Leon Constantin Maria Magdalena , Butnariu Lăcrămioara Ionela , Trandafirescu Mioara Florentina , Tîrnovanu Mihaela Camelia , Heredea Rodica , Pătrașcu Andrei Valentin , Botezat Doru , Cojocaru Elena
Published: July 2023

Skin cancers require a multidisciplinary approach. The updated guidelines introduce new insights into the management of these diseases. Melanoma (MM), the third most common skin cancer, a malignant melanocytic tumor, which is classified into four major histological subtypes, continues to have the potential to be a lethal disease. The mortality–incidence ratio is higher in Eastern European countries compared to Western European countries, which shows the need for better prevention and early detection in Eastern European countries. Basal cell carcinoma (BCC) and squamous cell carcinoma (cSCC) remain the top two skin cancers, and their incidence continues to grow. The gold standard in establishing the diagnosis and establishing the histopathological subtype in BCC and SCC is a skin biopsy. Sebaceous carcinoma (SeC) is an uncommon and potentially aggressive cutaneous malignancy showing sebaceous differentiation. It accounts for 0.7% of skin cancers and 3–6.7% of cancer-related deaths. Due to the rapid extension to the regional lymph nodes, SeC requires early treatment. The main treatment for sebaceous carcinoma is surgical treatment, including Mohs micrographic surgery, which has the advantage of complete margin evaluation and low recurrence rates. Primary cutaneous lymphomas (PCLs) are a heterogeneous group of lymphoproliferative diseases, with no evidence of extracutaneous determination at the moment of the diagnosis. PCLs have usually a very different evolution, prognosis, and treatment compared to the lymphomas that may secondarily involve the skin. The aim of our review is to summarize the important changes in the approach to treating melanoma, non-melanoma skin, cutaneous T and B cell lymphomas, and other types of skin cancers. For all skin cancers, optimal patient management requires a multidisciplinary approach including dermatology, medical oncology, and radiation oncology.
New Insights on the Role of Marinobufagenin from Bench to Bedside in Cardiovascular and Kidney Diseases
Authors: Carullo Nazareno , Fabiano Giuseppe , D'Agostino Mario , Zicarelli Maria Teresa , Musolino Michela , Presta Pierangela , Michael Ashour , Andreucci Michele , Bolignano Davide , Coppolino Giuseppe
Published: July 2023

Marinobufagenin (MBG) is a member of the bufadienolide family of compounds, which are natural cardiac glycosides found in a variety of animal species, including man, which have different physiological and biochemical functions but have a common action on the inhibition of the adenosine triphosphatase sodium-potassium pump (Na+/K+-ATPase). MBG acts as an endogenous cardiotonic steroid, and in the last decade, its role as a pathogenic factor in various human diseases has emerged. In this paper, we have collated major evidence regarding the biological characteristics and functions of MBG and its implications in human pathology. This review focused on MBG involvement in chronic kidney disease, including end-stage renal disease, cardiovascular diseases, sex and gender medicine, and its actions on the nervous and immune systems. The role of MBG in pathogenesis and the development of a wide range of pathological conditions indicate that this endogenous peptide could be used in the future as a diagnostic biomarker and/or therapeutic target, opening important avenues of scientific research.
Transcriptomic and Metabolomic Investigation on Leaf Necrosis Induced by ZmWus2 Transient Overexpression in Nicotiana benthamiana
Authors: Zhang Xianwen , Liang Shuang , Luo Biao , Zhou Zhongjing , Bao Jiandong , Fang Ruiqiu , Wang Fang , Song Xijiao , Liao Zhenfeng , Chen Guang , Wang Yan , Xu Fei , Teng Yi , Li Wanchang , Xu Shengchun , Lin Fu-Cheng
Published: July 2023

WUSCHEL (WUS) is a crucial transcription factor in regulating plant stem cell development, and its expression can also improve genetic transformation. However, the ectopic expression of WUS always causes pleiotropic effects during genetic transformation, making it important to understand the regulatory mechanisms underlying these phenomena. In our study, we found that the transient expression of the maize WUS ortholog ZmWus2 caused severe leaf necrosis in Nicotiana benthamiana. We performed transcriptomic and non-target metabolomic analyses on tobacco leaves during healthy to wilted states after ZmWus2 transient overexpression. Transcriptomic analysis revealed that ZmWus2 transformation caused active metabolism of inositol trisphosphate and glycerol-3-phosphate, while also upregulating plant hormone signaling and downregulating photosystem and protein folding pathways. Metabolomic analysis mainly identified changes in the synthesis of phenylpropanoid compounds and various lipid classes, including steroid synthesis. In addition, transcription factors such as ethylene-responsive factors (ERFs), the basic helix–loop–helix (bHLH) factors, and MYBs were found to be regulated by ZmWus2. By integrating these findings, we developed a WUS regulatory model that includes plant hormone accumulation, stress responses, lipid remodeling, and leaf necrosis. Our study sheds light on the mechanisms underlying WUS ectopic expression causing leaf necrosis and may inform the development of future genetic transformation strategies.
PRGF Membrane with Tailored Optical Properties Preserves the Cytoprotective Effect of Plasma Rich in Growth Factors: In Vitro Model of Retinal Pigment Epithelial Cells
Authors: Anitua Eduardo , Muruzabal Francisco , de la Fuente María , Del Olmo-Aguado Susana , Alkhraisat Mohammad H. , Merayo-Lloves Jesús
Published: July 2023

The present study evaluates the ability of a novel plasma rich in growth factors (PRGF) membrane with improved optical properties to reduce oxidative stress in retinal pigment epithelial cells (ARPE-19 cells) exposed to blue light. PRGF was obtained from three healthy donors and divided into four main groups: (i) PRGF membrane (M-PRGF), (ii) PRGF supernatant (S-PRGF), (iii) platelet-poor plasma (PPP) membrane diluted 50% with S-PRGF (M-PPP 50%), and (iv) M-PPP 50% supernatant (S-PPP 50%). ARPE-19 cells were exposed to blue light and then incubated with the different PRGF-derived formulations or control for 24 and 48 h under blue light exposure. Mitochondrial and cell viability, reactive oxygen species (ROS) production, and heme oxygenase-1 (HO-1) and ZO-1 expression were evaluated. Mitochondrial viability and cell survival were significantly increased after treatment with the different PRGF-derived formulations. ROS synthesis and HO-1 expression were significantly reduced after cell treatment with any of the PRGF-derived formulations. Furthermore, the different PRGF-derived formulations significantly increased ZO-1 expression in ARPE-19 exposed to blue light. The new PRGF membrane with improved optical properties and its supernatant (M-PPP 50% and S-PPP 50%) protected and reversed blue light-induced oxidative stress in ARPE-19 cells at levels like those of a natural PRGF membrane and its supernatant.
High-Confidence Placement of Fragments into Electron Density Using Anomalous Diffraction—A Case Study Using Hits Targeting SARS-CoV-2 Non-Structural Protein 1
Authors: Ma Shumeng , Mykhaylyk Vitaliy , Bowler Matthew W. , Pinotsis Nikos , Kozielski Frank
Published: July 2023

The identification of multiple simultaneous orientations of small molecule inhibitors binding to a protein target is a common challenge. It has recently been reported that the conformational heterogeneity of ligands is widely underreported in the Protein Data Bank, which is likely to impede optimal exploitation to improve affinity of these ligands. Significantly less is even known about multiple binding orientations for fragments (<300 Da), although this information would be essential for subsequent fragment optimisation using growing, linking or merging and rational structure-based design. Here, we use recently reported fragment hits for the SARS-CoV-2 non-structural protein 1 (nsp1) N-terminal domain to propose a general procedure for unambiguously identifying binding orientations of 2-dimensional fragments containing either sulphur or chloro substituents within the wavelength range of most tunable beamlines. By measuring datasets at two energies, using a tunable beamline operating in vacuum and optimised for data collection at very low X-ray energies, we show that the anomalous signal can be used to identify multiple orientations in small fragments containing sulphur and/or chloro substituents or to verify recently reported conformations. Although in this specific case we identified the positions of sulphur and chlorine in fragments bound to their protein target, we are confident that this work can be further expanded to additional atoms or ions which often occur in fragments. Finally, our improvements in the understanding of binding orientations will also serve to improve the rational optimisation of SARS-CoV-2 nsp1 fragment hits
Recent Advances in Anode Materials for Sodium-Ion Batteries
Authors: Bai Xue , Wu Nannan , Yu Gengchen , Li Tao
Published: July 2023

Although lithium-ion battery (LIB) technology has prevailed for years, the growing pressure and increased cost of lithium sources urge the rapid development of other promising energy storage devices. As a low-cost alternative, sodium-ion batteries (SIBs) with similar properties of electrochemical reaction have caught researchers’ attention. Nevertheless, great challenges of inferior reversible capacity and poor lifespan induced by the bigger ionic radius of sodium ions still exist. To solve these problems, improvements to anode materials prove to be an effective way. Herein, the latest research on promising anodes in SIBs is summarized, and the further prospects are also illustrated.
Ticks and Tick-Borne Pathogens from Wild Pigs in Northern and Central Florida
Authors: Mays Maestas Sarah E. , Campbell Lindsay P. , Milleson Michael P. , Reeves Lawrence E. , Kaufman Phillip E. , Wisely Samantha M.
Published: July 2023

Invasive wild pigs are distributed across much of the U.S. and are hosts to tick vectors of human disease. Herein, adult ticks were collected from 157 wild pigs in 21 northern and central Florida counties from 2019–2020 during removal efforts by USDA-APHIS Wildlife Services personnel and evaluated for their potential to be used as a method of tick-borne disease surveillance. Collected ticks were identified, screened for pathogens, and the effects of landscape metrics on tick community composition and abundance were investigated. A total of 1415 adult ticks of four species were collected. The diversity of tick species collected from wild pigs was comparable to collections made throughout the state with conventional surveillance methods. All species collected have implications for pathogen transmission to humans and other animals. Ehrlichia, Anaplasma-like, and Rickettsia spp. were detected in ticks collected from wild pigs. These results suggest that tick collection from wild pigs is a suitable means of surveillance for pathogens and vectors. The strongest drivers of variation in tick community composition were the developed open space and mixed forest landcover classes. Fragmented shrub/scrub habitat was associated with increased tick abundance. Similar models may be useful in predicting tick abundance and distribution patterns.
Reduced Invasiveness of Cardiopulmonary Bypass: The Mini-Circuit and the Micro-Cardioplegia
Authors: Carrel Thierry
Published: July 2023

The aim of cardiopulmonary bypass is the maintenance of a sufficient whole body perfusion and gas exchange during open or closed heart surgery procedure (coronary artery bypass grafting, valve repair and replacement, surgical intervention on the ascending aorta and/or aortic arch, repair of congenital malformations, and finally implantation of ventricular assist devices or cardiac transplantation). The main components of cardiopulmonary bypass are the pump that supplies the circulation and the oxygenator that regulates gas exchange. However, even though this technology has been extensively developed and improved over the last decades, one of the major drawbacks—which is the fact that blood has to flow through tubing systems with foreign surfaces—persists so far. Nevertheless, interesting innovations have been made more recently in order to better control the side-effects that culminate into a major activation of the coagulation and inflammatory systems: among them, miniaturization of the circuits, together with reduction of the priming volume and a simplified cardioplegia concept. All of these lead to a significant decrease of hemodilution and thereby a significant reduction of volume overload during surgery. In this brief review we will present some of these most interesting topics around minimized circuits and the simplified low-volume cardioplegia and discuss their potential benefits on the clinical outcome.
Development of Machine Learning-Based Web System for Estimating Pleural Effusion Using Multi-Frequency Bioelectrical Impedance Analyses
Authors: Nose Daisuke , Matsui Tomokazu , Otsuka Takuya , Matsuda Yuki , Arimura Tadaaki , Yasumoto Keiichi , Sugimoto Masahiro , Miura Shin-Ichiro
Published: July 2023

Background: Transthoracic impedance values have not been widely used to measure extravascular pulmonary water content due to accuracy and complexity concerns. Our aim was to develop a foundational model for a novel system aiming to non-invasively estimate the intrathoracic condition of heart failure patients. Methods: We employed multi-frequency bioelectrical impedance analysis to simultaneously measure multiple frequencies, collecting electrical, physical, and hematological data from 63 hospitalized heart failure patients and 82 healthy volunteers. Measurements were taken upon admission and after treatment, and longitudinal analysis was conducted. Results: Using a light gradient boosting machine, and a decision tree-based machine learning method, we developed an intrathoracic estimation model based on electrical measurements and clinical findings. Out of the 286 features collected, the model utilized 16 features. Notably, the developed model demonstrated high accuracy in discriminating patients with pleural effusion, achieving an area under the receiver characteristic curves (AUC) of 0.905 (95% CI: 0.870–0.940, p < 0.0001) in the cross-validation test. The accuracy significantly outperformed the conventional frequency-based method with an AUC of 0.740 (95% CI: 0.688–0.792, and p < 0.0001). Conclusions: Our findings indicate the potential of machine learning and transthoracic impedance measurements for estimating pleural effusion. By incorporating noninvasive and easily obtainable clinical and laboratory findings, this approach offers an effective means of assessing intrathoracic conditions.
Relationship between Inter-Eye Asymmetries in Corneal Hysteresis and Visual Field Severity in Patients with Primary Open-Angle Glaucoma
Authors: Akagi Tadamichi , Kato-Takano Yukiho , Miyamoto Daiki , Sakaue Yuta , Igarashi Ryoko , Iikawa Ryu , Arimatsu Mao , Miyajima Makoto , Togano Tetsuya , Fukuchi Takeo
Published: July 2023

This study investigated the influence of asymmetric corneal hysteresis (CH) on asymmetric visual field impairment between right and left eyes in patients with primary open-angle glaucoma (POAG) without a history of intraocular surgery. CH, corneal resistance factor (CRF), and corneal compensated intraocular pressure (IOPcc) were measured using the Ocular Response Analyzer. Differences between the eyes (right eye–left eye: DIFRL) and CH-based and in target parameters (higher CH eye–lower CH eye: DIFCH) were calculated in the same patient. In 242 phakic eyes of 121 patients, older age (p < 0.001), lower CH (p = 0.001), and lower CRF (p = 0.007) were significantly associated with worse standard automated perimetry (SAP) 24-2 mean deviation (MD). The DIFsRL in axial length (p = 0.003), IOPcc (p = 0.028), and CH (p = 0.001) were significantly associated with the DIFRL in SAP24-2 MD, but not in central corneal thickness (CCT), Goldmann applanation tonometry (GAT) measurement, and CRF. When dividing the patients into two groups based on the median of the CH DIFsCH (0.46), the DIFsCH in CRF (p < 0.001), IOPcc (p < 0.001), CCT (p = 0.004), SAP24-2 MD (p < 0.001), and SAP10-2 MD (p = 0.010) were significantly different between the groups. Large inter-eye asymmetry in CH is an important explanatory factor for disease worsening in patients with POAG.
Immediate Loaded Full-Arch Mandibular Rehabilitations in Younger vs. Elderly Patients: A Comparative Retrospective Study with 7-Year Follow-Up
Authors: Capparè Paolo , Tetè Giulia , D’Orto Bianca , Nagni Matteo , Gherlone Enrico Felice
Published: July 2023

The aim of this comparative retrospective clinical study was to assess the effect of age on immediate loaded full-arch mandibular rehabilitation in younger vs. elderly patients. Patients with an age between 45 and 60 years (younger group, YG) or with an age more or equal to 75 years (older group, OG), requiring a mandibular full-arch rehabilitation were scheduled for the present study. Implant and prosthetic failure, biological and prosthetic complications, and peri-implant marginal bone level changes were recorded until a 7-year follow-up. Sixty-six patients were included in the study; a total of 264 implants were placed and, in total, 66 “all-on-four” rehabilitations were delivered. In total, 33 patients were scheduled in the YG and 33 patients in the OG. At the 7-year follow-up, an overall implant failure rate of 1.14% was reported. Moreover, at the 7-year radiographic evaluation, peri-implant crestal bone loss averaged 1.12 ± 0.91 mm for the YG and 1.04 ± 1.01 mm for the OG. No statistically significant differences were found between the YG and OG except for the rate of peri-implantitis, which was statistically higher in the YG. The present study reported that immediate fixed mandibular full-arch rehabilitation is a viable procedure in elderly people of equal or more than 75 years of age.
Engaging in Awkward Social Interactions in a Virtual Environment Designed for Exposure-Based Psychotherapy for People with Generalized Social Anxiety Disorder: An International Multisite Study
Authors: Quintana Pamela , Bouchard Stéphane , Botella Cristina , Robillard Geneviève , Serrano Berenice , Rodriguez-Ortega Alejandro , Torp Ernst Mathias , Rey Beatriz , Berthiaume Maxine , Corno Giulia
Published: July 2023

The effectiveness of in virtuo exposure-based treatment of performance-only social anxiety disorder (SAD) has been demonstrated in several studies. However, few studies have validated virtual environments with participants suffering from generalized SAD. The goal of this study is to confirm the potential of a virtual environment in inducing anxiety in adults suffering from generalized SAD, compared to adults without SAD, when engaged in awkward social interactions. Differences between participants from two different countries were also explored. The sample consisted of 15 participants with SAD from Canada, 17 participants without SAD from Canada, 16 participants with SAD from Spain, and 21 participants without SAD from Spain. All participants were immersed in a control virtual environment and in an experimental virtual environment considered potentially anxiety-inducing for individuals with generalized SAD. As hypothesized, results showed that the experimental virtual environment induced a higher level of anxiety than the control environment among participants with SAD compared to those without SAD. The impact on anxiety of each socially threatening task performed during the experimental immersion was statistically significant. In terms of anxiety responses, no significant differences were found between participants from Canada and Spain. However, spatial presence and ecological validity were higher in Canadians than in Spaniards. Unwanted negative side effects induced by immersions in virtual reality were higher in the SAD group. This study highlights the importance for therapists to engage people with SAD in clinically relevant tasks while immersed in VR psychotherapeutic applications.
Intraspinal and Intracranial Neurotuberculosis, Clinical and Imaging Characteristics and Outcomes in Hospitalized Patients: A Cohort Study (2000–2022)
Authors: Corona-Nakamura Ana Luisa , Arias-Merino Martha Judith , Miranda-Novales María Guadalupe , Nava-Jiménez David , Delgado-Vázquez Juan Antonio , Bustos-Mora Rafael , Cisneros-Aréchiga Aldo Guadalupe , Aguayo-Villaseñor José Francisco , Hernández-Preciado Martha Rocio , Mireles-Ramírez Mario Alberto
Published: July 2023

Neurotuberculosis (neuroTB) is a devastating disease, and is difficult to diagnose. The aim of this study was to analyze the clinical and imaging characteristics, and outcomes of a retrospective cohort (2000–2022) of hospitalized patients diagnosed with intraspinal and intracranial neuroTB. This work was designed through clinical, laboratory and imaging findings. Variables included: demographic data, history of tuberculosis, neurological complications, comorbidities and outcomes. Morbi-mortality risk factors were identified by univariate analysis. The cohort included: 103 patients with intraspinal and 82 with intracranial neuroTB. During the study period, in-hospital mortality of 3% for intraspinal and 29.6% for intracranial neuroTB was estimated. Motor deficit was found in all patients with intraspinal neuroTB. Risk factors for the unfavorable outcome of patients with intraspinal neuroTB were: age ≥ 40 years, diabetes mellitus (DM), diagnostic delay, kyphosis and spondylodiscitis ≥ 3 levels of involvement. Among the patients with intracranial neuroTB, 79/82 (96.3%) had meningitis and 22 patients had HIV infection (10 of them died). Risk factors for mortality from intracranial neuroTB were: HIV infection, hydrocephalus, stroke, lymphopenia and disseminated and gastrointestinal TB. Patients with intraspinal neuroTB had a significant number of destroyed vertebrae that determined their neurological deficit status. The mortality burden in intracranial neuroTB was conditioned by HIV infection and renal transplantation patients.
Rhythm vs. Rate Control in Patients with Postoperative Atrial Fibrillation after Cardiac Surgery: A Systematic Review and Meta-Analysis
Authors: Ahmed Muneeb , Belley-Coté Emilie P. , Qiu Yuan , Belesiotis Peter , Tao Brendan , Wolf Alex , Kaur Hargun , Ibrahim Alex , Wong Jorge A. , Wang Michael K. , Healey Jeff S. , Conen David , Devereaux Philip James , Whitlock Richard P. , Mcintyre William F.
Published: July 2023

Background: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery; it is associated with morbidity and mortality. We undertook this review to compare the effects of rhythm vs. rate control in this population. Methods: We searched MEDLINE, Embase and CENTRAL to March 2023. We included randomized trials and observational studies comparing rhythm to rate control in cardiac surgery patients with POAF. We used a random-effects model to meta-analyze data and rated the quality of evidence using GRADE. Results: From 8,110 citations, we identified 8 randomized trials (990 patients). Drug regimens used for rhythm control included amiodarone in four trials, other class III anti-arrhythmics in one trial, class I anti-arrhythmics in four trials and either a class I or III anti-arrhythmic in one trial. Rhythm control compared to rate control did not result in a significant difference in length of stay (mean difference −0.8 days; 95% CI −3.0 to +1.4, I2 = 97%), AF recurrence within 1 week (130 events; risk ratio [RR] 1.1; 95%CI 0.6–1.9, I2 = 54%), AF recurrence up to 1 month (37 events; RR 0.9; 95%CI 0.5–1.8, I2 = 0%), AF recurrence up to 3 months (10 events; RR 1.0; 95%CI 0.3–3.4, I2 = 0%) or mortality (25 events; RR 1.6; 95%CI 0.7–3.5, I2 = 0%). Effect measures from seven observational studies (1428 patients) did not differ appreciably from those in randomized trials. Conclusions: Although atrial fibrillation is common after cardiac surgery, limited low-quality data guide its management. Limited available evidence suggests no clear advantage to either rhythm or rate control. A large-scale randomized trial is needed to inform this important clinical question.
Epidemiology of Coccidioidomycosis in the Veterans Health Administration, 2013–2022
Authors: Lucero-Obusan Cynthia , Deka Rishi , Schirmer Patricia , Oda Gina , Holodniy Mark
Published: July 2023

We describe the epidemiology of coccidioidomycosis among a national cohort of Veterans. Using electronic health record data from adults tested for coccidioidomycosis between 1 January 2013 and 31 December 2022, we analyzed differences in baseline demographics (age, sex, race/ethnicity, birth country, comorbidities, residence, and Charlson Comorbidity Index score) between 4204 coccidioidomycosis-test-positive and 63,322 test-negative Veterans. Log-binomial regression models with adjusted risk ratios (aRRs) were used to evaluate risk factors associated with coccidioidomycosis including dissemination, hospitalization, and mortality. Case counts and incidence rates were highest in select counties in Arizona and California where Coccidioides is endemic. Coccidioidomycosis-positive Veterans were younger, more likely to be male, and Philippine-born. The risk factors most highly associated with being coccidioidomycosis-positive included Native Hawaiian/Pacific Islander (aRR 1.068 [95%CI: 1.039–1.098]), Asian (aRR 1.060 [95%CI: 1.037–1.083]), Black (aRR 1.029 [95%CI: 1.022–1.036]), American Indian/Alaska Native (aRR 1.026 [95%CI: 1.004–1.048]) race, and Hispanic/Latino ethnicity (aRR 1.021 [95%CI: 1.013–1.028]). Black race (aRR: 1.058 [95%CI: 1.037–1.081]) and Hispanic/Latino ethnicity (aRR 1.018 [95%CI: 1.0003–1.036]) were also associated with disseminated coccidioidomycosis, strengthening the evidence for the association of coccidioidomycosis, including severe infections, with specific racial and ethnic groups. There were no statistically significant differences in hospitalization within 45 days of testing or 30-day all-cause mortality. Improving our understanding of coccidioidomycosis risk factors is important for targeted prevention strategies and to reduce delays in diagnosis and ineffective treatment.
Physiological Modeling of Hemodynamic Responses to Sodium Nitroprusside
Authors: Rinehart Joseph , Coeckelenbergh Sean , Srivastava Ishita , Cannesson Maxime , Joosten Alexandre
Published: July 2023

Background: Computational modeling of physiology has become a routine element in the development, evaluation, and safety testing of many types of medical devices. Members of the Food and Drug Administration have recently published a manuscript detailing the development, validation, and sensitivity testing of a computational model for blood volume, cardiac stroke volume, and blood pressure, noting that such a model might be useful in the development of closed-loop fluid administration systems. In the present study, we have expanded on this model to include the pharmacologic effect of sodium nitroprusside and calibrated the model against our previous experimental animal model data. Methods: Beginning with the model elements in the original publication, we added six new parameters to control the effect of sodium nitroprusside: two for the onset time and clearance rates, two for the stroke volume effect (which includes venodilation as a “hidden” element), and two for the direct effect on arterial blood pressure. Using this new model, we then calibrated the predictive performance against previously collected animal study data using nitroprusside infusions to simulate shock with the primary emphasis on MAP. Root-mean-squared error (RMSE) was calculated, and the performance was compared to the performance of the model in the original study. Results: RMSE of model-predicted MAP to actual MAP was lower than that reported in the original model, but higher for SV and CO. The individually fit models showed lower RMSE than using the population average values for parameters, suggesting the fitting process was effective in identifying improved parameters. Use of partially fit models after removal of the lowest variance population parameters showed a very minor decrement in improvement over the fully fit models. Conclusion: The new model added the clinical effects of SNP and was successfully calibrated against experimental data with an RMSE of <10% for mean arterial pressure. Model-predicted MAP showed an error similar to that seen in the original base model when using fluid shifts, heart rate, and drug dose as model inputs.
A Statistical Approach to Assess the Robustness of Radiomics Features in the Discrimination of Mammographic Lesions
Authors: Ponsiglione Alfonso Maria , Angelone Francesca , Amato Francesco , Sansone Mario
Published: July 2023

Despite mammography (MG) being among the most widespread techniques in breast cancer screening, tumour detection and classification remain challenging tasks due to the high morphological variability of the lesions. The extraction of radiomics features has proved to be a promising approach in MG. However, radiomics features can suffer from dependency on factors such as acquisition protocol, segmentation accuracy, feature extraction and engineering methods, which prevent the implementation of robust and clinically reliable radiomics workflow in MG. In this study, the variability and robustness of radiomics features is investigated as a function of lesion segmentation in MG images from a public database. A statistical analysis is carried out to assess feature variability and a radiomics robustness score is introduced based on the significance of the statistical tests performed. The obtained results indicate that variability is observable not only as a function of the abnormality type (calcification and masses), but also among feature categories (first-order and second-order), image view (craniocaudal and medial lateral oblique), and the type of lesions (benign and malignant). Furthermore, through the proposed approach, it is possible to identify those radiomics characteristics with a higher discriminative power between benign and malignant lesions and a lower dependency on segmentation, thus suggesting the most appropriate choice of robust features to be used as inputs to automated classification algorithms.
Recent Advances in Time-Sensitive Network Configuration Management: A Literature Review
Authors: Shi Boxin , Tu Xiaodong , Wu Bin , Peng Yifei
Published: July 2023

At present, many network applications are seeking to implement Time-Sensitive Network (TSN) technology, which not only furnishes communication transmission services that are deterministic, low-latency, highly dependable, and have ample bandwidth, but also enables unified configuration management, permitting different network types to function under a single management system. These characteristics enable it to be widely used in many fields such as industrial sensor and actuator networks, in-vehicle networks, data center networks, and edge computing. Nonetheless, TSN’s configuration management faces numerous difficulties and challenges related to network deployment, automated operation, and maintenance, as well as real-time and safety assurance, rendering it exceedingly intricate. In recent years, some studies have been conducted on TSN configuration management, encompassing various aspects such as system design, key technologies for configuration management, protocol enhancement, and application development. Nevertheless, there is a dearth of systematic summaries of these studies. Hence, this article aims to provide a comprehensive overview of TSN configuration management. Drawing upon more than 70 relevant publications and the pertinent standards established by the IEEE 802.1 TSN working group, we first introduce the system architecture of TSN configuration management from a macro perspective and then explore specific technical details. Additionally, we demonstrate its application scenarios through practical cases and finally highlight the challenges and future research directions. We aspire to provide a comprehensive reference for peers and new researchers interested in TSN configuration management.
Habitat Use, Terrestriality and Feeding Behaviour of Javan Slow Lorises in Urban Areas of a Multi-Use Landscape in Indonesia
Authors: Karimloo Laura , Campera Marco , Imron Muhammad Ali , Rakholia Shrey , Mehta Abhinav , Hedger Katherine , Nekaris K.A.I.
Published: July 2023

Urban areas are rapidly expanding into natural habitats worldwide. When species are threatened with habitat loss, it is vital to understand how they will respond or adapt to the change in their environment. One primate species threatened by habitat loss is the fully arboreal Javan slow loris (Nycticebus javanicus). This non-leaping species not only relies on canopy continuity but is also subject to capture for illegal wildlife trade, especially in anthropogenic landscapes where they are easier to catch. We examine the use of urban areas by Javan slow lorises in terms of habitat use as well as feeding and terrestriality behaviours in the municipality of Cipaganti in West Java, Indonesia. For this study, we observed Javan slow lorises from May 2018 to April 2020 for two dry periods and two wet periods. We combined home ranges and core areas with a land cover classification of the area to understand the composition of the loris habitat. We also included feeding and terrestriality data to determine the ratio of these activities within each land cover class. We found that approximately half of their territory falls into natural areas (bamboo patches: 45–60%), and the other half is in human land use areas (agriculture, shade gardens, urban areas, and fallow land). Urban areas ranged from 0 to 54% of an individual loris’s habitat, with the proportion of urban land cover being higher in some individuals’ core areas than in their home ranges. Only urban areas showed a variation between periods, with p-values of 0.06 and 0.002 for home ranges and core areas, respectively, showing a significant increase usage during dry periods. Of all feeding observations, 4% occurred in urban areas with nectar being the most common feeding item. We recorded thirteen different food species in urban areas with Calliandra calothrysus being the most frequent. We found that 7% of terrestriality events occurred in urban areas. The findings from this study show that human land use areas cover a significant portion of the Javan slow lorises habitat in this region, further emphasising the need to consider the needs of these Critically Endangered primates when developing natural habitats into those of human managed landscapes. The same principles are true for the large number of species that are able to persist in urban areas in a world increasingly dominated by humans.
The Impact of the Rural–Urban Migration of Chinese Farmers on the Use of Rural Homesteads: A Threshold Model Analysis
Authors: Yao Rui , Ye Jianping , Song Lei
Published: July 2023

China’s urbanisation process is unique compared to that of other developed economies in that while the rural population is migrating to the cities in large numbers, the area of rural homestead use also continues to increase. This research uses macro data and a threshold model to further analyse this phenomenon of “farmers leaving while rural homestead increasing”. Specifically, we focus on the mechanisms of action, development patterns and regional differences in the impact of the rate of rural–urban migration (RRUM) on the rate of increase in the area of rural homesteads (IARH), and discuss the spatial spillover effects of the impact between the two. The results of the research show that: (1) There is an “inverted U-shaped” double threshold effect on the impact of RRUM on IARH. (2) Rural population density and regional urban–rural income disparity are used as threshold variables, respectively, resulting in a sudden change in the relationship between RRUM and IARH. (3) The threshold effect of RRUM on IARH mainly exists in the central and western regions, non-minority nationality areas, non-provincial capital cities and non-resource-based cities. (4) The RRUM can not only directly affect the local IARH, but also indirectly affect the surrounding areas through spatial spillover effects. Our research provides critical insights for policy makers on the reform of the rural homestead system and urbanisation development strategies in different regions.
Comparison between Low-Level and High-Intensity Laser Therapy as an Adjunctive Treatment for Knee Osteoarthritis: A Randomized, Double-Blind Clinical Trial
Authors: Ahmad Mohd Azzuan , Moganan Mageswari , A Hamid Mohamad Shariff , Sulaiman Norhuda , Moorthy Ushantini , Hasnan Nazirah , Yusof Ashril
Published: July 2023

Background: Low-level (LLLT) and high-intensity laser therapy (HILT) can be beneficial additions to knee osteoarthritis (KOA) rehabilitation exercises; however, it is still being determined which electrophysical agent is more effective. Aim: To compare the effects of LLLT and HILT as adjuncts to rehabilitation exercises (LL + EX and HL + EX) on clinical outcomes in KOA. Methods: Thirty-four adults with mild-to-moderate KOA were randomly allocated to either LL + EX or HL + EX (n = 17 each). Both groups underwent their respective intervention weekly for twelve weeks: LL + EX (400 mW, 830 nm, 10 to 12 J/cm2, and 400 J per session) or HL + EX (5 W, 1064 nm, 19 to 150 J/cm2, and 3190 J per session). The laser probe was placed vertically in contact with the knee and moved in a slow-scan manner on the antero-medial/lateral sides of the knee joint. Participants’ Knee Injury and Osteoarthritis Outcome Score (KOOS), Numerical Pain Rating Scale (NPRS), active knee flexion, and Timed Up-and-Go test (TUG) were assessed. Results: Post intervention, both groups showed improvements in their KOOS, NPRS, active knee flexion, and TUG scores compared to baseline (p < 0.01). The mean difference of change in KOOS, NPRS, and active knee flexion scores for the HL + EX group surpassed the minimal clinically important difference threshold. In contrast, the LL + EX group only demonstrated clinical significance for the NPRS scores. Conclusions: Incorporating HILT as an adjunct to usual KOA rehabilitation led to significantly higher improvements in pain, physical function, and knee-related disability compared to LLLT applied in scanning mode.