Immunophenotypic and Gene Expression Analyses of the Inflammatory Microenvironment in High-Grade Oral Epithelial Dysplasia and Oral Lichen Planus.

BACKGROUND: Oral lichen planus (OLP) and oral epithelial dysplasia (OED) present diagnostic challenges due to clinical and histologic overlap. This study explores the immune microenvironment in OED, hypothesizing that immune signatures could aid in diagnostic differentiation and predict malignant transformation. METHODS: Tissue samples from OED and OLP cases were analyzed using immunofluorescence/immunohistochemistry (IF/IHC) for CD4, CD8, CD163/STAT1, and PD-1/PDL-1 expression. RNA-sequencing was performed on the samples, and data was subjected to CIBERSORTx analysis for immune cell composition. Gene Ontology analysis on the immune differentially expressed genes was also conducted. RESULTS: In OED, CD8 + T-cells infiltrated dysplastic epithelium, correlating with dysplasia severity. CD4 + lymphocytes increased in the basal layer. STAT1/CD163 + macrophages correlated with CD4 + intraepithelial distribution. PD-1/PDL-1 expression varied. IF/IHC analysis revealed differential immune cell composition between OED and OLP. RNA-sequencing identified upregulated genes associated with cytotoxic response and immunosurveillance in OED. Downregulated genes were linked to signaling, immune cell recruitment, and tumor suppression. CONCLUSIONS: The immune microenvironment distinguishes OED and OLP, suggesting diagnostic potential. Upregulated genes indicate cytotoxic immune response in OED. Downregulation of TRADD, CX3CL1, and ILI24 implies dysregulation in TNFR1 signaling, immune recruitment, and tumor suppression. This study contributes to the foundation for understanding immune interactions in OED and OLP, offering insights into future objective diagnostic avenues.

Response of Central Giant Cell Granuloma of the Jaw to Imatinib.

Central giant cell granuloma of the jaw (CGCJ) can be locally aggressive and result in facial and dental deformity. A child with CGCJ was treated surgically and with denosumab with a response but life-threatening toxicity. Imatinib, a tyrosine kinase inhibitor, was prescribed based on clinical similarities between CGCJ and cherubism, for which Imatinib has been effective. Within 2 months, a computed tomographic scan showed significant ossification, which increased over the following 8 months. This case suggests that tyrosine kinase inhibitors may be an effective option, and one with limited toxicity, for CGCJ.

Malignant Lymphoproliferative Disorders of the Oral and Maxillofacial Region: Report of Two Institutions.

BACKGROUND: Report of the incidence of malignant hematologic neoplasms in the oral cavity according to the experience of the two oral and maxillofacial pathology institutions in North Carolina, USA. METHODS: A 10-year retrospective review was carried out in the records of patients at ECU SoDM and UNC Adams SoD. Age, sex, location of the lesion, clinical impression, initial diagnosis, and the expression immunohistochemical and molecular markers were recorded for each subject. All diagnoses were reviewed according to the 2016 revision of the WHO classification of lymphoid neoplasms. RESULTS: A total of 318 records from both institutions were reviewed. Seventy males and 68 females with an average age of 60.7 comprised the study population. The most common neoplasm encountered was plasma cell myeloma, followed by diffuse large B-cell lymphoma, B-lymphoblastic lymphoma, and follicular lymphoma. We encountered primarily intraosseous tumors, with the posterior mandible and posterior maxilla being the most common locations. Twelve cases were identified initially as a periapical radiolucency. CONCLUSION: Our findings are concurrent with the existing literature regarding epidemiologic data. However, the type and location of tumors encountered do not, as the most common lymphoma in the oral cavity is diffuse large B-cell lymphoma, typically present in soft tissue. To aid in diagnosis and treatment, the collection of data should continue over time so that eventually, a more specific diagnostic profile of North Carolina residents with these neoplasms can be made.

Crop fertilisation potential of phosphorus in hydrochars produced from sewage sludge.

Sewage sludges are a rich underused source of phosphorus (P) which contributes to environmental degradation, yet if recaptured, could return significant amounts of P to agricultural systems. Hydrothermal carbonisation (HTC) can efficiently recover P, with the added ability to transform P species into potentially more desirable forms for direct application to crops. P dynamics in hydrochars have primarily examined P speciation and chemical extractability as indicators of P bioavailability, but few studies directly evaluate the agronomic effectiveness of hydrochars as P fertilisers. As such, there is a clear need to assess the suitability of hydrochar as a source of bioavailable P in plant systems and the influence of HTC synthesis conditions. Response Surface Modelling of HTC synthesis conditions (pH, temperature and time), revealed initial pH significantly influence P distribution. Mild conditions of 180 °C for 30 min at pH 8.0 maximised P recovery (99%) along with carbon (62%) and nitrogen (43%) in hydrochars. Systematic characterisation of hydrochar P by chemical extraction and P L2,3-edge X-ray absorption near edge spectroscopy revealed H2O, NaHCO3 and NaOH- P fractions were significantly (p < 0.05) reduced in all hydrochars, while HCl-P fraction increased with HTC temperatures at pH 7. In contrast, P L2,3-edge XANES spectra were remarkably similar in raw sludges and corresponding hydrochars, regardless of HTC temperature or pH, revealing P was predominantly present as ferric phosphate with some hydroxyapatite. Multiple linear regression modelling suggested a significant relationship between chemical extractability and P bioavailability to wheat present in the raw sludges and hydrochars. This research provides further insight into the potential to use hydrothermal treatment for recovery and agricultural reuse of P, the importance of operational conditions on P transformation and the relationship between P speciation and bioavailability. The value of sewage sludge in a more sustainable global P cycle is also highlighted.

A Comprehensive Review on Smart Grids: Challenges and Opportunities.

Recently, the operation of distribution systems does not depend on the state or utility based on centralized procedures, but rather the decentralization of the decisions of the distribution companies whose objectives are the efficiency of interconnectivity. Therefore, distribution companies are exposed to greater risks, and due to this, the need to make decisions based on increasingly reliable models has grown up considerably. Therefore, we present a survey of key aspects, technologies, protocols, and case studies of the current and future trend of Smart Grids. This work proposes a taxonomy of a large number of technologies in Smart Grids and their applications in scenarios of Smart Networks, Neural Networks, Blockchain, Industrial Internet of Things, or Software-Defined Networks. Therefore, this work summarizes the main features of 94 research articles ranging the last four years. We classify these survey, according Smart Grid Network Topologies, because it can group as the main axis the sensors applied to Smart Grids, as it shows us the interconnection forms generalization of the Smart Networks with respect to the sensors found in a home or industry.

VirtualCPR: Virtual Reality Mobile Application for Training in Cardiopulmonary Resuscitation Techniques.

Deaths due to heart diseases are a leading cause of death in Mexico. Cardiovascular diseases are considered a public health problem because they produce cardiorespiratory arrests. During an arrest, cardiac and/or respiratory activity stops. A cardiorespiratory arrest is rapidly fatal without a quick and efficient intervention. As a response to this problem, the VirtualCPR system was designed in the present work. VirtualCPR is a mobile virtual reality application to support learning and practicing of basic techniques of cardiopulmonary resuscitation (CPR) for experts or non-experts in CPR. VirtualCPR implements an interactive virtual scenario with the user, which is visible by means of employment of virtual reality lenses. User's interactions, with our proposal, are by a portable force sensor for integration with training mannequins, whose development is based on an application for the Android platform. Furthermore, this proposal integrates medical knowledge in first aid, related to the basic CPR for adults using only the hands, as well as technological knowledge, related to development of simulations on a mobile virtual reality platform by three main processes: (i) force measurement and conversion, (ii) data transmission and (iii) simulation of a virtual scenario. An experiment by means of a multifactorial analysis of variance was designed considering four factors for a CPR session: (i) previous training in CPR, (ii) frequency of compressions, (iii) presence of auditory suggestions and (iv) presence of color indicator. Our findings point out that the more previous training in CPR a user of the VirtualCPR system has, the greater the percentage of correct compressions obtained from a virtual CPR session. Setting the rate to 100 or 150 compressions per minute, turning on or off the auditory suggestions and turning the color indicator on or off during the session have no significant effect on the results obtained by the user.

SARS-CoV-2 infection of the oral cavity and saliva.

Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae. Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.

CRTC1/MAML2 directs a PGC-1α-IGF-1 circuit that confers vulnerability to PPARγ inhibition.

Mucoepidermoid carcinoma (MEC) is a life-threatening salivary gland cancer that is driven primarily by a transcriptional coactivator fusion composed of cyclic AMP-regulated transcriptional coactivator 1 (CRTC1) and mastermind-like 2 (MAML2). The mechanisms by which the chimeric CRTC1/MAML2 (C1/M2) oncoprotein rewires gene expression programs that promote tumorigenesis remain poorly understood. Here, we show that C1/M2 induces transcriptional activation of the non-canonical peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) splice variant PGC-1α4, which regulates peroxisome proliferator-activated receptor gamma (PPARγ)-mediated insulin-like growth factor 1 (IGF-1) expression. This mitogenic transcriptional circuitry is consistent across cell lines and primary tumors. C1/M2-positive tumors exhibit IGF-1 pathway activation, and small-molecule drug screens reveal that tumor cells harboring the fusion gene are selectively sensitive to IGF-1 receptor (IGF-1R) inhibition. Furthermore, this dependence on autocrine regulation of IGF-1 transcription renders MEC cells susceptible to PPARγ inhibition with inverse agonists. These results yield insights into the aberrant coregulatory functions of C1/M2 and identify a specific vulnerability that can be exploited for precision therapy.

Non-Parametric Evaluation Methods of the Brain Activity of a Bottlenose Dolphin during an Assisted Therapy.

Dolphin-Assisted Therapies (DAT) are alternative therapies aimed to reduce anxiety levels, stress relief and physical benefits. This paper is focused on measuring and analyzing dolphins brain activity when DAT is taking place in order to identify if there is any differences in female dolphin's neuronal signal when it is interacting with control or intervention subjects, performing our research in Delfiniti, Ixtapa, Mexico facilities. We designed a wireless and portable electroencephalographic single-channel signal capture sensor to acquire and monitor the brain activity of a female bottle-nose dolphin. This EEG sensor was able to show that dolphin activity at rest is characterized by high spectral power at slow-frequencies bands. When the dolphin participated in DAT, a 23.53% increment in the 12-30 Hz frequency band was observed, but this only occurred for patients with some disease or disorder, given that 0.5-4 Hz band keeps it at 17.91% when there is a control patient. Regarding the fractal or Self-Affine Analysis, we found for all samples studied that at the beginning the dolphin's brain activity behaved as a self-affine fractal described by a power-law until the fluctuations of voltage reached the crossovers, and after the crossovers these fluctuations left this scaling behavior. Hence, our findings validate the hypothesis that the participation in a DAT of a Patient with a certain disease or disorder modifies the usual behavior of a female bottle-nose dolphin.

Defining a no-reference image quality assessment by means of the self-affine analysis.

In this paper we propose a novel Blind Image Quality Assessment via Self-Affine Analysis (BIQSAA) method by considering the wavelet transform as a linear operation that decomposes a complex signal into elementary blocks at different scales or resolutions. BIQSAA decomposes a distorted image into a set of wavelet planes ω λ, ϕ of different spatial frequencies λ and spatial orientations ϕ, and it transforms these wavelet planes into one-dimension vector Ω using a Hilbert scanning. From the vector Ω there were obtained their wavelet coefficient fluctuations estimated by the inverse of the Hurst exponent in decibels, whose scaling-law or fractal behavior was obtained by applying Fractal Geometry or Self-Affine Analysis. The scaling exponents calculated for the coefficient fluctuation behavior of Image Lena at 24bpp, at 1.375bpp, and at 0.50bpp were H 24b p p = 0.0395, H 1.375b p p = 0.0551, and H 0.50b p p = 0.0612, respectively. Our experiments show that BIQSAA algorithm improves in 14.36% the Human Visual System correlation, respect to the four state-of-the-art No-Reference Image Quality Assessments.

Biomedical Signal Acquisition Using Sensors under the Paradigm of Parallel Computing.

There are several pathologies attacking the central nervous system and diverse therapies for each specific disease. These therapies seek as far as possible to minimize or offset the consequences caused by these types of pathologies and disorders in the patient. Therefore, comprehensive neurological care has been performed by neurorehabilitation therapies, to improve the patients' life quality and facilitating their performance in society. One way to know how the neurorehabilitation therapies contribute to help patients is by measuring changes in their brain activity by means of electroencephalograms (EEG). EEG data-processing applications have been used in neuroscience research to be highly computing- and data-intensive. Our proposal is an integrated system of Electroencephalographic, Electrocardiographic, Bioacoustic, and Digital Image Acquisition Analysis to provide neuroscience experts with tools to estimate the efficiency of a great variety of therapies. The three main axes of this proposal are: parallel or distributed capture, filtering and adaptation of biomedical signals, and synchronization in real epochs of sampling. Thus, the present proposal underlies a general system, whose main objective is to be a wireless benchmark in the field. In this way, this proposal could acquire and give some analysis tools for biomedical signals used for measuring brain interactions when it is stimulated by an external system during therapies, for example. Therefore, this system supports extreme environmental conditions, when necessary, which broadens the spectrum of its applications. In addition, in this proposal sensors could be added or eliminated depending on the needs of the research, generating a wide range of configuration limited by the number of CPU cores, i.e., the more biosensors, the more CPU cores will be required. To validate the proposed integrated system, it is used in a Dolphin-Assisted Therapy in patients with Infantile Cerebral Palsy and Obsessive-Compulsive Disorder, as well as with a neurotypical one. Event synchronization of sample periods helped isolate the same therapy stimulus and allowed it to be analyzed by tools such as the Power Spectrum or the Fractal Geometry.

Integrated Single-Cell Atlases Reveal an Oral SARS-CoV-2 Infection and Transmission Axis.

Despite signs of infection, the involvement of the oral cavity in COVID-19 is poorly understood. To address this, single-cell RNA sequencing data-sets were integrated from human minor salivary glands and gingiva to identify 11 epithelial, 7 mesenchymal, and 15 immune cell clusters. Analysis of SARS-CoV-2 viral entry factor expression showed enrichment in epithelia including the ducts and acini of the salivary glands and the suprabasal cells of the mucosae. COVID-19 autopsy tissues confirmed in vivo SARS-CoV-2 infection in the salivary glands and mucosa. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 expression and SARS-CoV-2 RNA. Matched nasopharyngeal and saliva samples found distinct viral shedding dynamics and viral burden in saliva correlated with COVID-19 symptoms including taste loss. Upon recovery, this cohort exhibited salivary antibodies against SARS-CoV-2 proteins. Collectively, the oral cavity represents a robust site for COVID-19 infection and implicates saliva in viral transmission.

Neurodynamics of Patients during a Dolphin-Assisted Therapy by Means of a Fractal Intraneural Analysis.

The recent proliferation of sensor technology applications in therapies for children's disabilities to promote positive behavior among such children has produced optimistic results in developing a variety of skills and abilities in them. Dolphin-Assisted Therapy (DAT) has also become a topic of public and research interest for these disorders' intervention and treatment. This work exposes the development of a system that controls brain-computer interaction when a patient with different abilities undergoes a DAT. To develop the proposed system, TGAM1, i.e., ThinkGear-AM1 series of NeuroSky company, was used, connecting it to an isolated Bluetooth 4.0 communication protocol from a brackish and humid environment, and a Notch Filter was applied to reduce the input noise. In this way, at Definiti Ixtapa-Mexico facilities, we explored the behavior of three children with Infantile Spastic Cerebral Palsy (Experiment 1), as well as the behavior of Obsessive Compulsive Disorder and neurotypic children (Experiment 2). This was done applying the Power Spectrum Density (PSD) and the Self-Affine Analysis (SSA) from Electroencephalogram (EEG) biosignals. The EEG Raw data were time series showing the cerebral brain activity (voltage versus time) before and during DAT for the Experiment 1, and before, during DAT and after for the Experiment 2. Likewise, the EEW RAW data were recorded by the first frontopolar electrode (FP1) by means of an EEG biosensor TGAM1 Module. From the PSD we found that in all child patients a huge increment of brain activity during DAT regarding the before and after therapy periods around 376.28%. Moreover, from the SSA we found that the structure function of the all five child patients displayed an antipersistent behavior, characterized by σ ∝ δ t H , for before, during DAT and after. Nonetheless, we propose that one way to assess whether a DAT is being efficient to the child patients is to increase the during DAT time when the samples are collected, supposing the data fitting by a power law will raise the time, displaying a persistent behavior or positive correlations, until a crossover appears and the curve tends to be horizontal, pointing out that our system has reached a stationary state.

Working collaboratively across schools to promote oral health education through interprofessional education.

PURPOSE: The Association of American Medical Colleges and American Dental Education Association have identified oral health knowledge, skills, and attitudes shared by both medical and dental professionals. Although oral health was deemed an essential competency for medical practitioners, our state struggled to ensure learners received proper training. This training deficit resulted in conducting a needs assessment and implementing an oral health interprofessional module at our schools. METHODS: First-year medical students and clinical faculty were emailed surveys in 2016 to obtain baseline information. A team of faculty and students from the Schools of Medicine and Dentistry reviewed the curriculum to determine where to augment oral health content. An oral health module to teach a basic head, neck, and oral examination to first-year medical students during their patient-centered care small-group sessions was implemented and evaluated. RESULTS: Only 13.6% of faculty respondents were aware of national oral health competency recommendations, and <50% rated oral health important for primary care physicians (PCPs) to include in history, physical exam, or oral health counseling. On baseline, ≤25% of PCP respondents reported integrating the listed skills in their practice, and most indicated lacking expertise to teach oral health. Teaching sessions were rated helpful by students and faculty. After the teaching sessions, ratings on the importance of including oral health significantly increased from baseline. CONCLUSION: Collaboration between Schools of Dentistry and Medicine successfully integrated oral health into medical school curriculum and improved the tutors' attitudes of its importance.

Energy-Efficient Industrial Internet of Things Software-Defined Network by Means of the Peano Fractal.

The Industrial Internet of Things (IIoT) network generates great economic benefits in processes, system installation, maintenance, reliability, scalability, and interoperability. Wireless sensor networks (WSNs) allow the IIoT network to collect, process, and share data of different parameters among Industrial IoT sense Node (IISN). ESP8266 are IISNs connected to the Internet by means of a hub to share their information. In this article, a light-diffusion algorithm in WSN to connect all the IISNs is designed, based on the Peano fractal and swarm intelligence, i.e., without using a hub, simply sharing parameters with two adjacent IINSs, assuming that any IISN knows the parameters of the rest of these devices, even if they are not adjacent. We simulated the performance of our algorithm and compared it with other state-of-the-art protocols, finding that our proposal generates a longer lifetime of the IIoT network when few IISNs were connected. Thus, there is a saving-energy of approximately 5% but with 64 nodes there is a saving of more than 20%, because the IIoT network can grow in a 3 n way and the proposed topology does not impact in a linear way but log 3 , which balances energy consumption throughout the IIoT network.

Fractal Characterization of Stochastic Series Fluctuations of Children with Reading Disorders.

Reading is an emerging process from human brain activity. This process sometimes is subject to disorders which has been studied from the performance of studies that provide data that are treated with qualitative and quantitative linear tools to obtain the average behavior determined and the causality of it. This research focuses on the nonlinear quantitative study of reading disorder and in this way fractal geometry and roughness interface growth theory approach were selected to be used in the processing of brain wave quantification (EEG). From the EEG of children with and without reading disorders in the State of Mexico (experimental and control group) were built time series of standard deviation for each of the 19 channels distributed in cerebral cortex. The self-affinity of these time series (treated as interfaces in motion) is studied by the scaling behavior of their structure functions. It was found that the behavior of the time series of children with reading problems (experimental group) and without them (control group) is similar to the Family-Vicsek scaling dynamic for a kinetic roughening of moving interface.

Global deletion of Optineurin results in altered type I IFN signaling and abnormal bone remodeling in a model of Paget's disease.

Genome-wide association studies (GWAS) have identified Optineurin (OPTN) as genetically linked to Paget's disease of the bone (PDB), a chronic debilitating bone remodeling disorder characterized by localized areas of increased bone resorption and abnormal bone remodeling. However, only ~10% of mouse models with a mutation in Optn develop PDB, thus hindering the mechanistic understanding of the OPTN-PDB axis. Here, we reveal that 100% of aged Optn global knockout (Optn-/-) mice recapitulate the key clinical features observed in PDB patients, including polyostotic osteolytic lesions, mixed-phase lesions, and increased serum levels of alkaline phosphatase (ALP). Differentiation of primary osteoclasts ex vivo revealed that the absence of Optn resulted in an increased osteoclastogenesis. Mechanistically, Optn-deficient osteoclasts displayed a significantly decreased type I interferon (IFN) signature, resulting from both defective production of IFNß and impaired signaling via the IFNα/ßR, which acts as a negative feedback loop for osteoclastogenesis and survival. These data highlight the dual roles of OPTN in the type I IFN response to restrain osteoclast activation and bone resorption, offering a novel therapeutic target for PDB. Therefore, our study describes a novel and essential mouse model for PDB and define a key role for OPTN in osteoclast differentiation.