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Abstract Cement mediated peri-implantitis accounts for 1.9–75% of dental implant failures associated with peri-implant diseases. This study evaluated the biological impact of dental cements on osseointegrated implants using Lewis rats. Twenty-two rats were distributed into 6 groups: negative control (NC) soft diet (SD), and hard diet (HD); positive control SD and HD (n = 3); Implant + bio-ceramic Cement (BC) SD and HD which included contralateral Sham sites (n = 5). Titanium implants were placed on either side of the maxillae and allowed to heal for 14 days. Later, both sides of experimental groups underwent a re-entry surgery to simulate clinical cementation. The right side received 0.60 mg of BC. At 14 days post cement application, maxillae were harvested for clinical, microtomographic, and histological evaluations. Clinical and microtomographic evaluations indicated evidence of extensive inflammation and circumferential bone resorption around BC implants in comparison to NC. Histology revealed cement particles surrounded by inflammatory infiltrate in the implant area accompanied by biofilm for SD groups. Both sides of BC indicated intensive bone resorption accompanied by signs of osteolysis when compared to NC. Cemented groups depicted significantly lower bone to implant contact when compared to NC. In conclusion, residual cement extravasation negatively impacted osseointegrated implants after re-entry surgeries.

Objectives To analyse the effectiveness of a physical exercise programme guided by a mobile health technology system (COVIDReApp) for patients with post-acute COVID-19 syndrome. This syndrome is a multisystem disease that occurs in people with a history of COVID-19 between 1 and 3 months after the onset of the disease. This study will assess the impact of the intervention on fatigue, post-exertional dyspnoea, quality of life, pain severity, physical fitness, anxiety, depression and cognitive function. We also aim to analyse whether there are associations between the variables studied and the evolution of these associations during follow-up. Design A single-blind randomised controlled trial. Methods One hundred patients diagnosed with post-acute COVID-19 will be enrolled and randomly assigned to two groups. The experimental group will perform the intervention through a physical exercise programme guided by the COVIDReApp system, whereas the control group will perform the programme in paper format. Study outcomes will be collected at baseline and at 4, 12 and 24 weeks. Student's t -tests or Mann–Whitney U -tests will be used to analyse differences between groups, mixed ANOVA for differences over time and longitudinal structural equations for associations between variables at follow-up. Discussion This study is based on current evidence regarding exercise prescription recommendations for patients with post-acute COVID-19 syndrome. Our intervention is supported by a solid theoretical framework; however, challenges include tailoring the physical exercise programme to everyone's predominant symptoms and ensuring adherence to the programme. Trial registration number NCT05725538.

Summary: Background: Gut L-type enteroendocrine cells (EECs) are intestinal chemosensory cells that secrete satiety hormones GLP-1 and PYY in response to activation of G-protein coupled receptors (GPCRs) by luminal components of nutrient digestion and microbial fermentation. Regulator of G-protein Signaling (RGS) proteins are negative regulators of GPCR signaling. The expression profile of RGS in EECs, and their potential role in satiety hormone secretion and obesity is unknown. Methods: Transcriptomic profiling of RGS was completed in native colonic EECs was completed using single-cell RNA sequencing (scRNA-Seq) in lean and obesity, and human jejunal EECs with data obtained from a publicly available RNAseq dataset (GSE114853). RGS validation studies were completed using whole mucosal intestinal tissue obtained during endoscopy in 61 patients (n = 42 OB, n = 19 Lean); a subset of patients’ postprandial plasma was assayed for GLP-1 and PYY. Ex vivo human intestinal cultures and in vitro NCI–H716 cells overexpressing RGS9 were exposed to GLP-1 secretagogues in conjunction with a nonselective RGS-inhibitor and assayed for GLP-1 secretion. Findings: Transcriptomic profiling of colonic and jejunal enteroendocrine cells revealed a unique RGS expression profile in EECs, and further within GLP-1+ L-type EECs. In obesity the RGS expression profile was altered in colonic EECs. Human gut RGS9 expression correlated positively with BMI and negatively with postprandial GLP-1 and PYY. RGS inhibition in human intestinal cultures increased GLP-1 release from EECs ex vivo. NCI–H716 cells overexpressing RGS9 displayed defective nutrient-stimulated GLP-1 secretion. Interpretation: This study introduces the expression profile of RGS in human EECs, alterations in obesity, and suggests a role for RGS proteins as modulators of GLP-1 and PYY secretion from intestinal EECs. Funding: AA is supported by the NIH(C-Sig P30DK84567, K23 DK114460), a Pilot Award from the Mayo Clinic Center for Biomedical Discovery, and a Translational Product Development Fund from The Mayo Clinic Center for Clinical and Translational Science Office of Translational Practice in partnership with the University of Minnesota Clinical and Translational Science Institute.

Melanoma showcases a complex interplay of genetic alterations and intra- and inter-cellular morphological changes during metastatic transformation. While pivotal, the role of specific mutations in dictating these changes still needs to be fully elucidated. Telomerase promoter mutations (TERTp mutations) significantly influence melanoma's progression, invasiveness, and resistance to various emerging treatments, including chemical inhibitors, telomerase inhibitors, targeted therapy, and immunotherapies. We aim to understand the morphological and phenotypic implications of the two dominant monoallelic TERTp mutations, C228T and C250T, enriched in melanoma metastasis. We developed isogenic clonal cell lines containing the TERTp mutations and utilized dual-color expression reporters steered by the endogenous Telomerase promoter, giving us allelic resolution. This approach allowed us to monitor morpholomic variations induced by these mutations. TERTp mutation-bearing cells exhibited significant morpholome differences from their wild-type counterparts, with increased allele expression patterns, augmented wound-healing rates, and unique spatiotemporal dynamics. Notably, the C250T mutation exerted more pronounced changes in the morpholome than C228T, suggesting a differential role in metastatic potential. Our findings underscore the distinct influence of TERTp mutations on melanoma's cellular architecture and behavior. The C250T mutation may offer a unique morpholomic and systems-driven advantage for metastasis. These insights provide a foundational understanding of how a non-coding mutation in melanoma metastasis affects the system, manifesting in cellular morpholome.

The availability of high-resolution satellite images has accelerated the creation of new datasets designed to tackle broader remote sensing (RS) problems. Although popular tasks, such as scene classification, have received significant attention, the recent release of the Land-1.0 RS dataset marks the initiation of endeavors to estimate land-use and land-cover (LULC) fraction values per RGB satellite image. This challenging problem involves estimating LULC composition, i.e., the proportion of different LULC classes from satellite imagery, with major applications in environmental monitoring, agricultural/urban planning, and climate change studies. Currently, supervised deep learning models—the state-of-the-art in image classification—require large volumes of labeled training data to provide good generalization. To face the challenges posed by the scarcity of labeled RS data, self-supervised learning (SSL) models have recently emerged, learning directly from unlabeled data by leveraging the underlying structure. This is the first article to investigate the performance of SSL in LULC fraction estimation on RGB satellite patches using in-domain knowledge. We also performed a complementary analysis on LULC scene classification. Specifically, we pretrained Barlow Twins, MoCov2, SimCLR, and SimSiam SSL models with ResNet-18 using the Sentinel2GlobalLULC small RS dataset and then performed transfer learning to downstream tasks on Land-1.0. Our experiments demonstrate that SSL achieves competitive or slightly better results when trained on a smaller high-quality in-domain dataset of 194 877 samples compared to the supervised model trained on ImageNet-1k with 1 281 167 samples. This outcome highlights the effectiveness of SSL using in-distribution datasets, demonstrating efficient learning with fewer but more relevant data.

Background & Aims: Autophagy plays roles in esophageal pathologies both benign and malignant. Here, we aim to define the role of autophagy in esophageal epithelial homeostasis. Methods: We generated tamoxifen-inducible, squamous epithelial-specific Atg7 (autophagy related 7) conditional knockout mice to evaluate effects on esophageal homeostasis and response to the carcinogen 4-nitroquinoline 1-oxide (4NQO) using histologic and biochemical analyses. We fluorescence-activated cell sorted esophageal basal cells based on fluorescence of the autophagic vesicle (AV)-identifying dye Cyto-ID and then subjected these cells to transmission electron microscopy, image flow cytometry, three-dimensional organoid assays, RNA sequencing, and cell cycle analysis. Three-dimensional organoids were subjected to passaging, single-cell RNA sequencing, cell cycle analysis, and immunostaining. Results: Genetic autophagy inhibition in squamous epithelium resulted in increased proliferation of esophageal basal cells under homeostatic conditions and also was associated with significant weight loss in mice treated with 4NQO that further displayed perturbed epithelial tissue architecture. Esophageal basal cells with high AV level (Cyto-IDHigh) displayed limited organoid formation capability on initial plating but passaged more efficiently than their counterparts with low AV level (Cyto-IDLow). RNA sequencing suggested increased autophagy in Cyto-IDHigh esophageal basal cells along with decreased cell cycle progression, the latter of which was confirmed by cell cycle analysis. Single-cell RNA sequencing of three-dimensional organoids generated by Cyto-IDLow and Cyto-IDHigh cells identified expansion of 3 cell populations and enrichment of G2/M-associated genes in the Cyto-IDHigh group. Ki67 expression was also increased in organoids generated by Cyto-IDHigh cells, including in basal cells localized beyond the outermost cell layer. Conclusions: Autophagy contributes to maintenance of the esophageal proliferation-differentiation gradient. Esophageal basal cells with high AV level exhibit limited proliferation and generate three-dimensional organoids with enhanced self-renewal capacity.

Abstract Plk1-interacting checkpoint helicase (PICH) is a DNA translocase involved in resolving ultrafine anaphase DNA bridges and, therefore, is important to safeguard chromosome segregation and stability. PICH is overexpressed in various human cancers, particularly in lymphomas such as Burkitt lymphoma, which is caused by MYC translocations. To investigate the relevance of PICH in cancer development and progression, we have combined novel PICH-deficient mouse models with the Eμ-Myc transgenic mouse model, which recapitulates B-cell lymphoma development. We have observed that PICH deficiency delays the onset of MYC-induced lymphomas in Pich heterozygous females. Moreover, using a Pich conditional knockout mouse model, we have found that Pich deletion in adult mice improves the survival of Eμ-Myc transgenic mice. Notably, we show that Pich deletion in healthy adult mice is well tolerated, supporting PICH as a suitable target for anticancer therapies. Finally, we have corroborated these findings in two human Burkitt lymphoma cell lines and we have found that the death of cancer cells was accompanied by chromosomal instability. Based on these findings, we propose PICH as a potential therapeutic target for Burkitt lymphoma and for other cancers where PICH is overexpressed.

Background: Esophageal organoids from a variety of pathologies including cancer are grown in Advanced Dulbecco’s Modified Eagle Medium-Nutrient Mixture F12 (hereafter ADF). However, the currently available ADF-based formulations are suboptimal for normal human esophageal organoids, limiting the ability to compare normal esophageal organoids with those representing a given disease state. Methods: We have utilized immortalized normal human esophageal epithelial cell (keratinocyte) lines EPC1 and EPC2 and endoscopic normal esophageal biopsies to generate three-dimensional (3D) organoids. To optimize the ADF-based medium, we evaluated the requirement of exogenous epidermal growth factor (EGF) and inhibition of transforming growth factor-(TGF)-β receptor-mediated signaling, both key regulators of the proliferation of human esophageal keratinocytes. We have modeled human esophageal epithelial pathology by stimulating esophageal 3D organoids with interleukin (IL)-13, an inflammatory cytokine, or UAB30, a novel pharmacological activator of retinoic acid signaling. Results: The formation of normal human esophageal 3D organoids was limited by excessive EGF and intrinsic TGFβ-receptor-mediated signaling. Optimized HOME0 improved normal human esophageal organoid formation. In the HOME0-grown organoids, IL-13 and UAB30 induced epithelial changes reminiscent of basal cell hyperplasia, a common histopathologic feature in broad esophageal disease conditions including eosinophilic esophagitis. Conclusions: HOME0 allows modeling of the homeostatic differentiation gradient and perturbation of the human esophageal epithelium while permitting a comparison of organoids from mice and other organs grown in ADF-based media.

Objective: To describe the use of psychiatric medication and related health service utilization among college students receiving care on- and off-campus. Participants and methods: 3959 students from a large southern university participated in the Healthy Minds Study in May 2018. Results: Of students surveyed, 17.6% took psychiatric medication in the last year. Of these students, 22.0% received prescriptions on-campus, 61.7% received prescriptions off-campus, 6.4% received them both on- and off-campus, and 9.9% took medication without a prescription. Nonwhite, international, and younger students were more likely to utilize on-campus rather than off-campus psychiatric medication services (p < 0.05). Satisfaction with health services did not differ by location. Conclusions: The majority of students received psychiatric prescriptions off- rather than on-campus. While satisfaction with both on- and off-campus health services is equally high, minority, international, and younger students are more likely to seek care on- rather than off-campus.

The improvement of the conversion efficiency of the photovoltaic panels, the efficiency of the inverters for connection to the electrical grid, and the dynamism of the distribution systems have had a direct impact on how energy is being generated in the residential, industrial, commercial, and transport sectors. This article shows an experimental study related to the analysis of a Building Integrated Photovoltaic (BIPV) system and its performance. A monitoring process was applied during three years to evaluate the energy production, CO2 emissions and economical savings. The paper presents the energy performance results of a 9.5 kW BIPV system installed in the El Paso residential area, located in Colombia (in the city of Girardot, at 74.7799 longitude and 4.3828 latitude). The main results during the first 3 years of monitoring (March 2019–March 2022) show that the average energy generation of the system has been 9,910.5 kWh/year; the environmental impact has been 3,645.38 kgCO2-equ. for the first three years of operation and the economic savings by generating clean energy have been 4,776.24 USD.

Despite of scientific efforts to evaluate economically the photovoltaic plants integrating the costs generated by the technical behavior of the system, few studies have demonstrated the behavior of the economic parameters from experimental data obtained from the photovoltaic plants in real-time operation. On the other hand, the cost analysis carried out by various authors breaks down the equation for calculating the Levelized cost of energy in independent terms without considering the marketing options of local markets in remote regions.This article discusses the results of a lead–acid battery system monitored over six years of operation. The system is part of a 20 kWp independent, modular photovoltaic power plant and is divided into two parallel circuits, each consisting of 24 batteries. Technical parameters such as state of charge, Pb-A system voltage, temperature, and charge/discharge currents were monitored, along with power flow before and after the Pb-A system inverter. The incremental charge/discharge efficiency between two parallel circuits, the duration of the charge and discharge cycles, and the Coulombic efficiency were evaluated from the measured data. A statistical analysis of the state of charge was performed to specify the energy delivered from the series of battery banks. This allowed for an evaluation and understanding of the operational performance of the photovoltaic system from a technical and economic point of view. The average minimum and maximum state of charge for bank 1 was 78.9% and 99.96%, respectively, and for bank 2 was 78.15% and 99.83%, respectively, for the monitored period. The efficiency of the incremental cycle varies for Sb1 from 92% to 99% and for Sb2 between 80% and 99%. From the monitoring of these parameters and using actual costs, the Levelized Cost of Electricity was determined for various discount rates.