Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of hyporheic zone characteristics on the structure and activity of microbial assemblages

Summary The hyporheic zone is a pivotal environment for biogeochemical processes in riverine ecosystems. However, the responses of hyporheic microbial assemblage structure and activity to environmental variables remain poorly understood. The objective of this study was to determine the influence of hyporheic zone characteristics on microbial assemblages in three French rivers (Usses, Isere and Drome). For each river, microbial structure (assemblage composition and abundance) and activity were measured at three sites with contrasting environmental characteristics (e.g. effective streambed porosity, oxygen and nutrient concentrations). Firstly, we expected that the structure and activity of the hyporheic microbial assemblage would be significantly affected by the environmental characteristics of the hyporheic zone. We also expected a strong relationship between the structure and activity of hyporheic microbial communities in the Usses River, due to greater spatial heterogeneity (i.e. greater porosity differences between the studied sites) compared with the two other rivers. Our results showed that porosity reduction, greatest in the Usses River, affected the exchanges of flows and energy through the hyporheic zone and, consequently, led to a distinct microbial assemblage composition in comparison with the two other rivers. Significant relationships between bacterial assemblage structure and activity were detected for the Usses and Drome rivers, due to the greater spatial variability in sediment and physicochemical variables observed in these two rivers than in the Isere. Hyporheic zone characteristics (sediment permeability, water chemistry, particulate organic matter) appear to be the key factors controlling microbial structure and activity in riverine environments. As the hyporheic zone is essential for biogeochemical processes, including those attenuating pollution, a better quantification of the influences of environmental factors controlling microbial activity is needed to understand and predict ecosystem processes in the hyporheic zone.
The Imaging Features and Clinical Associations of a Novel Tau PET Tracer—18F-APN1607 in Alzheimer Disease

Supplemental digital content is available in the text. Purpose of the Report In vivo tau PET imaging could help clarify the spatial distribution of tau deposition in Alzheimer disease (AD) and aid in the differential diagnosis of tauopathies. To date, there have been no in vivo 18F-APN1607 tau PET studies in patients with AD. Methods We applied tau tracer in 12 normal controls (NCs) and 10 patients in the mild to moderate stage of probable AD. Detailed clinical information, cognitive measurements, and disease severity were documented. Regional SUV ratios (SUVRs) from 18F-AV-45 (florbetapir), 18F-APN1607 PET images, and regional gray matter (GM) atrophic ratios were calculated for further analysis. Results Quantitative analyses showed significantly elevated SUVRs in the frontal, temporal, parietal, occipital lobes, anterior and posterior cingulate gyri, precuneus, and parahippocampal region (all P’s < 0.01) with medium to large effect sizes (0.44–0.75). The SUVRs from 18F-APN1607 PET imaging showed significant correlations with the Alzheimer’s Disease Assessment Scale (ADAS-cog) scores (all P’s < 0.01) and strong correlation coefficients (R2 ranged from 0.54 to 0.68), even adjusted for age and sex effects. Finally, the SUVRs from 18F-APN1607 PET imaging of the parahippocampal region showed rapid saturation as the ADAS-cog scores increased, and the SUVRs of the posterior cingulate gyrus and the temporal, frontal, parietal, and occipital regions slowly increased. The combined SUVRs from amyloid, tau PET, and regional GM atrophic ratio showed regional specific patterns as the ADAS-cog scores increased. Conclusions Our findings suggest that the 18F-APN1607 tau tracer correlated well with cognitive changes and demonstrated the spatial pattern of amyloid, tau deposition, and GM atrophy in the progression of AD.
A Hybrid CMOS-Memristive Approach to Designing Deep Generative Models

Deep learning and its applications have gained tremendous interest recently in both academia and industry. Restricted Boltzmann machines (RBMs) offer a key methodology to implement deep learning paradigms. This brief presents a novel approach for realizing hybrid CMOS-memristive-based deep generative models (DGMs). In our proposed DGM architecture, HfOx-based (filamentary-type switching) memristive devices are extensively used for realizing both computational as well as storage functions, such as: 1) synapses (weights); 2) internal neuron-state storage; 3) stochastic neuron activation; and 4) programmable signal normalization. To validate the proposed scheme, we have simulated two different architectures: 1) deep belief network (DBN) for classification and 2) stacked denoising autoencoder for the reconstruction of handwritten digits from the MNIST data set. The maximum test accuracy achieved by pretraining of the proposed DBN was 92.6%, whereas the best case mean squared error (mse) achieved by pretraining of the proposed SDA network was 0.046. When the proposed model-based weights are used for weight initialization, they offer a significant advantage in terms of learning performance in comparison with randomized initialization.
Morphologic and Immunohistochemical Characteristics of Fluorescent In Situ Hybridization Confirmed TFE3-Gene Fusion Associated Renal Cell Carcinoma

TFE3-fusion associated renal cell carcinoma (TFE3-RCC) accounts for up to 5% adults and 40% of childhood RCC. Their comprehensive immunohistochemical (IHC) profile in correlation to fluorescence in situ hybridization (FISH) testing and their role in the diagnostic approach are not well documented because of lacking published data. FISH confirmed TFE3-RCC between years 2010 and 2020 were identified from institutional electronic database and retrospectively reviewed. Eighty-five TFE3-RCC were identified. Seventy-six of 85 (89.4%) TFE3-RCC cases had positive TFE3 expression, with diffuse and strong/moderate TFE3 expression in 45 (54.2%). Three (3.5%) TFE3-RCC had negative TFE3 expression whereas 6 (7%) cases had equivocal TFE3 expression. On the other hand, positive TFE3-IHC expression was observed in 17/29 (58.6%) TFE3-FISH negative RCC cases, although only 8 (27.5%) had diffuse and moderate/strong TFE3 expression. Diffuse and strong TFE3-IHC expression was statistically significant in predicting TFE3-FISH positivity (P<0.0001) regardless of morphologic features. After univariate and multivariate analyses, TFE3-IHC was the only parameter with significant predictive value for detecting positive TFE3-FISH (P<0.0001). On univariate analysis, sex, classic morphology, age, negative AE1/AE3 or cytokeratin 7 were not predictive of TFE3-FISH positivity. Diffuse and strong nuclear TFE3-IHC expression is significantly associated with TFE3-FISH positivity and can be used as a surrogate marker to confirm translocation associated cases. TFE3-rearranged RCCs show variable histomorphologic features and TFE3-FISH should be performed in cases presenting at a younger age or, regardless of the age, tumors with unusual morphology. Despite previous reports, negative pancytokeratin and positive cathepsin K expression may not be reliable markers for TFE3-RCC.
Role of COX-2 Promoter Methylation and Helicobacter pylori Infection in Impaired Gastric Ulcer Healing

Helicobacter pylori ( H. pylori ) infection causes aberrant DNA methylation of various genes in the gastric mucosa. Cyclooxygenases (COX) play a critical role in peptic ulcer development and healing. Human COX-2 has CpG islands (CGIs) in its promoter region, suggest- ing a possible epigenetic regulation. Here, we evaluated COX-2 promoter methylation in the gastric mucosa of patients with various gastric diseases and found that COX-2 meth- ylation levels in the gastric mucosa were significantly increased in patients with H. pylori infection. We further investigated the roles of COX-2 during the healing of acetic acid- induced gastric ulcers in H. pylori -infected Mongolian gerbils (MGs). While COX-2 mRNA expression levels on the edges of acetic acid-induced gastric ulcers were significantly increased after ulcer induction in MGs in the absence of H. pylori , no such induction was observed in H. pylori -infected gastric mucosa. Cloning of the MG COX-2 gene revealed abundant CGIs in the promoter region. COX-2 mRNA expression in MG-derived gastric carcinoma MGC2 cells was significantly increased by addition of the demethylating agent 5-Aza-dC. Additionally, COX-2 methylation levels were higher in H. pylori -infected MG gastric mucosa than in control mucosa. These results indicated that epigenetic inhibition of COX-2 mRNA induced by H. pylori impairs gastric ulcer healing. possible between COX and of 5′-CpG (CGIs) the range of genes involved COX-2 has CGIs in its promoter region, suggests regulation. discuss our recent results on the epigenetic regulation of COX-2 activity in H. pylori -infected gastric mucosa of humans and Mongolian gerbils (MGs), and the possible relationship between COX-2 methylation and delayed gastric ulcer healing. sustained inflammation in the gastric mucosa. This chronic inflammation causes aberrant DNA methylation in various genes. The COX-2 promoter regions in both MGs and humans contain abundant CGIs. COX plays critical roles in peptic ulcer development and healing, and both COX-1 and COX-2 are necessary for the gastric mucosal defense system. COX-1 is a housekeeping enzyme, which maintains microcirculation and mucous production. During ulcer healing, COX-2 is expressed at the margin of an ulcer, and COX-2-derived PGs induce various growth factors to promote mucosal healing and angiogenesis. Ulcer healing is delayed in H. pylori infected-MG stomachs, which is the best model of H. pylori infection in humans. We showed that COX-2 mRNA induction during ulcer healing was impaired in H. pylori -infected-MG stomachs. The COX-2 promoter region is methylated in both H. pylori -infected human and MG gastric mucosa. These CGIs are also methylated in human Kato III cells and MGC2 gastric carcinoma cells. COX-2 mRNA expression in these cells is restored by treatment with a demethylating agent. In H. pylori -infected gastric mucosa, COX-2 promoter methylation appears to be involved in the impaired COX-2 mRNA induction typically observed during ulcer healing, which leads to delayed ulcer healing.
Analysis of PAX8 immunohistochemistry in lung cancers: a meta-analysis

Background In this meta-analysis, we aimed to evaluate the PAX8 immunohistochemical expressions in primary lung cancers and metastatic cancers to the lung. Methods We identified and reviewed relevant articles from the PubMed databases. Ultimately, 18 articles were included in this meta-analysis. PAX8 expression rates were analyzed and compared between primary and metastatic lung cancers. Results The PAX8 expression rate in primary lung cancers was 0.042 (95% confidence interval [CI], 0.025 to 0.071). PAX8 expression rates of small cell (0.129; 95% CI, 0.022 to 0.496) and non-small cell carcinomas of the lung (0.037; 95% CI, 0.022 to 0.061) were significantly different (p=.049 in a meta-regression test). However, the PAX8 expression rates of adenocarcinoma (0.013; 95% CI, 0.006 to 0.031) and squamous cell carcinoma (0.040; 95% CI, 0.016 to 0.097) were not significantly different. PAX8 expression rates of metastatic carcinomas to the lung varied, ranging from 1.8% to 94.9%. Metastatic carcinomas from the lung to other organs had a PAX8 expression rate of 6.3%. The PAX8 expression rates of metastatic carcinomas from the female genital organs, kidneys, and thyroid gland to the lung were higher than those of other metastatic carcinomas. Conclusions Primary lung cancers had a low PAX8 expression rate regardless of tumor subtype. However, the PAX8 expression rates of metastatic carcinomas from the female genital organs, kidneys, and thyroid were significantly higher than those of primary lung cancers.
Synergistic effects of Cinnamomum cassia L. essential oil in combination with polymyxin B against carbapenemase-producing Klebsiella pneumoniae and Serratia marcescens

Multidrug resistance prompts the search for new sources of antibiotics with new targets at bacteria cell. To investigate the antibacterial activity of Cinnamomum cassia L. essential oil (CCeo) alone and in combination with antibiotics against carbapenemase-producing Klebsiella pneumoniae and Serratia marcescens. The antimicrobial susceptibility of the strains was determined by Vitek® 2 and confirmed by MALDI-TOF/TOF. The antibacterial activity of CCeo and its synergism with antibiotics was determined using agar disk diffusion, broth microdilution, time-kill, and checkboard methods. The integrity of the bacterial cell membrane in S. marcescens was monitored by protein leakage assay. CCeo exhibited inhibitory effects with MIC = 281.25 μg. mL-1. The association between CCeo and polymyxin B showed a decrease in terms of viable cell counts on survival curves over time after a 4 hour-treatment with a FIC index value of 0.006. Protein leakage was observed with increasing concentrations for CCeo and CCeo + polymyxin B treatments. CCeo showed antibacterial activity against the studied strains. When associated with polymyxin B, a synergistic effect was able to inhibit bacterial growth rapidly and consistently, making it a potential candidate for the development of an alternative treatment and drug delivery system for carbapenemase-producing strains.
Transcriptomic Classification of Neurons Innervating Teeth

Toothache is a common painful consequence of damage to the teeth, particularly when coupled to infection. Clinical restoration of tooth integrity, sometimes involving physical and chemical sterilization of the tooth with nerve fiber ablation (i.e., endodontic therapy), generally alleviates pain and allows long-lasting dental function. These observations raise questions regarding the biological role of tooth-innervating fibers. Here, we determined the transcriptomic diversity of the sensory neurons that can be retrogradely labeled from mouse molar teeth. Our results demonstrate that individual molars are each targeted by a dedicated population of about 50 specialized trigeminal neurons. Transcriptomic profiling identifies the majority of these as expressing markers of fast-conducting neurons, with about two-thirds containing nociceptive markers. Our data provide a new view of dental innervation, extending previous reports that used candidate gene approaches. Importantly, almost all retrogradely labeled neurons, including nociceptors, express the recently characterized mechanosensor Piezo2, an ion channel that endows cells with sensitivity to gentle touch. Intriguingly, about a quarter of the labeled neurons do not appear to be nociceptors, perhaps insinuating a role for them in discriminative touch. We hypothesize that dental neurons are capable of providing mechanosensitive information to drive rapid behavioral responses and protect teeth from damage. Damage to the teeth and exposure of the large population of molar nociceptors may trigger prolonged or abnormal activation driving toothache. Future studies examining the responses of these transcriptomically defined classes of neurons will help define their significance in oral sensation.
Regulation of Endothelial Barrier Function

Abstract The vascular endothelium lining the inner surface of blood vessels serves as the first interface for circulating blood components to interact with cells of the vascular wall and surrounding extravascular tissues. In addition to regulating blood delivery and perfusion, a major function of vascular endothelia, especially those in exchange microvessels (capillaries and postcapillary venules), is to provide a semipermeable barrier that controls blood–tissue exchange of fluids, nutrients, and metabolic wastes while preventing pathogens or harmful materials in the circulation from entering into tissues. During host defense against infection or tissue injury, endothelial barrier dysfunction occurs as a consequence as well as cause of inflammatory responses. Plasma leakage disturbs fluid homeostasis and impairs tissue oxygenation, a pathophysiological process contributing to multiple organ dysfunction associated with trauma, infection, metabolic disorder, and other forms of disease. In this book, we prov.
Effects of Diabetes Education on Emotional Distress in Patients with Type 2 Diabetes—An Experimental Study

Objective: It was to evaluate the effect of diabetes education on emotional distress in type 2 diabetes patients treated with oral medications. Methods: The experimental study took place in Albania and overall, 200 type 2 diabetes patients were enrolled (in both groups, intervention, and control) treated with oral medications, having levels of Glycated hemoglobin HbA1c > 6.5% as well the absence of associated diseases such as dementia and psychiatric disorders. Patients were randomly selected from the medical registry of family physicians in the Tirana region. Patients were screened for the emotional distress before and after the intervention with the self-administered questionnaire Problem Areas in Diabetes PAID 5. In addition, the levels of HbA1c in % were evaluated before and after intervention in both groups. Only intervention group underwent four diabetes education sessions offered by trained nursing staff while the control group continued the previous regime. The questionnaire reliability analysis was estimated by the Cronbach alpha coefficient. To compare the groups the t-test was used and the value of p < 0.05 was considered significant. Results: Mean age of patients in intervention and control group was respectively 54.03 ±9.57 and 55.82 ± 7.86. Before and after health education PAID 5 scores for the intervention group were respectively 11.3 vs. 8.75 while for the control group 11.9 vs. 11.35, p = 0.018. Levels of HbA1c% before and after education for the intervention group were 7.02 vs. 6.2 while for the control group 6.9 vs. 6.8, p = 0.001. Positive and significant correlation (r = 0.321, p = 0.001) was between level of emotional distress and the age of the patients. Conclusions: The study found that besides better control of diabetes, additional education of diabetic patients seemed to significantly improve the level of emotional distress due to diabetes in diabetic patients.
Metagenomic approaches in microbial ecology: an update on whole-genome and marker gene sequencing analyses

Metagenomics and marker gene approaches, coupled with high-throughput sequencing technologies, have revolutionized the field of microbial ecology. Metagenomics is a culture-independent method that allows the identification and characterization of organisms from all kinds of samples. Whole-genome shotgun sequencing analyses the total DNA of a chosen sample to determine the presence of micro-organisms from all domains of life and their genomic content. Importantly, the whole-genome shotgun sequencing approach reveals the genomic diversity present, but can also give insights into the functional potential of the micro-organisms identified. The marker gene approach is based on the sequencing of a specific gene region. It allows one to describe the microbial composition based on the taxonomic groups present in the sample. It is frequently used to analyse the biodiversity of microbial ecosystems. Despite its importance, the analysis of metagenomic sequencing and marker gene data is quite a challenge. Here we review the primary workflows and software used for both approaches and discuss the current challenges in the field.
Nonsteroidal Anti-inflammatory Drugs vs Cognitive Behavioral Therapy for Arthritis Pain: A Randomized Withdrawal Trial.

Importance Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for knee osteoarthritis. However, they are associated with uncertain long-term clinical benefit and significant toxic effects. Objective To evaluate whether discontinuing NSAIDs and engaging in a telephone-based cognitive behavioral therapy (CBT) program is noninferior to continuing NSAIDs for patients with knee osteoarthritis. Design, Setting, and Participants The Stopping NSAIDs for Arthritis Pain multicenter randomized withdrawal trial was conducted for 364 patients taking NSAIDs for knee osteoarthritis pain on most days of the week for at least 3 months between September 1, 2013, and September 30, 2018. Analysis was performed on an intent-to-treat basis. Interventions Participants discontinued their current NSAID and took 15 mg per day of meloxicam daily during a 2-week run-in period. Those who remained eligible were randomized in a 1:1 ratio to receive meloxicam or placebo for 4 weeks (blinded phase 1). Participants receiving meloxicam then continued this medication for 10 weeks, while those receiving placebo participated in a 10-week CBT program (unblinded phase 2). Main Outcomes and Measures The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at 4 weeks with the noninferiority margin set at 1. Secondary outcomes included the area under the curve of the pain score after 4 weeks as well as the WOMAC pain score, area under the curve of the pain score, WOMAC disability score, and global impression of change after treatment at 14 weeks. Results A total of 180 participants (161 men; mean [SD] age, 58. 2 [11.8] years) were randomized to receive placebo followed by CBT, and a total of 184 participants (154 men; mean [SD] age, 58.5 [10.0] years) were randomized to receive meloxicam. After adjustment for baseline pain and study site, the estimated mean difference in WOMAC pain score between the placebo and meloxicam groups after 4 weeks was 1.4 (95% CI, 0.8-2.0; noninferiority test P = .92). At week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (95% CI, 0.2-1.4; noninferiority P = .28). There was no statistically significant difference in the global impression of change (mean difference in scores, -0.2; 95% CI, -0.4 to 0.1; P = .15) or lower extremity disability (mean difference in scores, 0.9; 95% CI, -1.4 to 3.2; P = .45) between the 2 groups after 14 weeks. Conclusions and Relevance Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam. However, the WOMAC pain score differences between the 2 groups were small, and there were no statistically significant differences in participants' global impression of change or function after 14 weeks. Trial Registration ClinicalTrials.gov Identifier: NCT01799213.