Miracle-dz/UniFAR-FTUs huggingface dataset:
Noise-Induced Vascular Dysfunction, Oxidative Stress, and Inflammation Are Improved by Pharmacological Modulation of the NRF2/HO-1 Axis

Vascular oxidative stress, inflammation, and subsequent endothelial dysfunction are consequences of traditional cardiovascular risk factors, all of which contribute to cardiovascular disease. Environmental stressors, such as traffic noise and air pollution, may also facilitate the development and progression of cardiovascular and metabolic diseases. In our previous studies, we investigated the influence of aircraft noise exposure on molecular mechanisms, identifying oxidative stress and inflammation as central players in mediating vascular function. The present study investigates the role of heme oxygenase-1 (HO-1) as an antioxidant response preventing vascular consequences following exposure to aircraft noise. C57BL/6J mice were treated with the HO-1 inducer hemin (25 mg/kg i.p.) or the NRF2 activator dimethyl fumarate (DMF, 20 mg/kg p.o.). During therapy, the animals were exposed to noise at a maximum sound pressure level of 85 dB(A) and a mean sound pressure level of 72 dB(A). Our data showed a marked protective effect of both treatments on animals exposed to noise for 4 days by normalization of arterial hypertension and vascular dysfunction in the noise-exposed groups. We observed a partial normalization of noise-triggered oxidative stress and inflammation by hemin and DMF therapy, which was associated with HO-1 induction. The present study identifies possible new targets for the mitigation of the adverse health effects caused by environmental noise exposure. Since natural dietary constituents can achieve HO-1 and NRF2 induction, these pathways represent promising targets for preventive measures.
LED and HPS Supplementary Light Differentially Affect Gas Exchange in Tomato Leaves

Using light emitting diodes (LED) instead of conventionally used high pressure sodium (HPS) lamps as a supplemental light source in greenhouses results in a higher efficacy (µmol light per J electricity) and makes it possible to customize the light spectrum. To explore the effects of LED and HPS on gas exchange, thermal relations, photosynthesis, and water status of young tomato plants, seven genotypes were grown in a greenhouse under LED (95% red, 5% blue) or HPS lamps in four experiments differing in the fraction of lamp light over natural light. HPS lights emit a broader spectrum of red (40%), green–yellow (50%), blue (5%), and far-red (5%) and a substantial amount of infrared radiation (heat). Young tomato plants grown under LED showed lower leaf temperature and higher stomatal density, stomatal conductance (gs) and transpiration rate (E) than plants grown under HPS; this may be due to the different supplemental light spectrum. The young plants grown under LED tended to have increased photosynthetic capacity. Furthermore, the water stress indices CWSI and IG, which were obtained using thermal imaging, were positively correlated with gas exchange-derived gs and E, putting forward the use of thermal imaging for the phenotyping of transpiration. Under LED light, photosynthetic gas exchange was generally increased, which agreed with the water stress indices. The extent of this increase was genotype-dependent. All differences between LED and HPS were smaller in the experiments where the fraction of lamp light over natural light was smaller.
Diet–Cognition Associations Differ in Mild Cognitive Impairment Subtypes

Cognitive function is not generally associated with diet, and there is debate over that association. Moreover, little is known about such associations with the specific cognitive domains and subtypes of mild cognitive impairment (MCI). We analyzed data of 4309 Chinese adults aged 55 and over from the Community-based Cohort Study on Nervous System Diseases from 2018–2019. Dietary habits were assessed at inclusion using a validated semi-quantitative food frequency questionnaire. Cognitive function of the participants was measured by using the Montreal Cognitive Assessment. Analyses were performed using multiple logistic regression and quantile regression with adjustment for socio-demographic, lifestyle, and health-related factors. Compared with normal cognition participants, those with a worse cognition state were characterized as being an older age and lower economic level. After adjustment for potential factors, participants with higher consumption of rice, legumes, fresh vegetables, fresh fruit, pork, poultry, fish, and nuts tended to have higher scores of global cognitive function and domains, and to have lower odds of MCI, while those with higher consumption levels of wheat and eggs had worse cognition, compared with the corresponding bottom consumption level of each food. Participants with a medium consumption level of beef or mutton had 57% (OR: 1.57, 95%CI: 1.07–2.32) higher odds of aMCI-SD, whereas they had 50% (OR: 0.50, 95%CI: 0.34–0.73) lower odds of naMCI-MD. Similarly, the highest consumption level of dairy was positively associated with the odds of aMCI-SD (OR:1.51, 95%CI:1.00–2.29), but inversely linked to the odds of naMCI-SD (OR: 0.60, 95%CI: 0.38–0.93) and naMCI-MD (OR: 0.49, 95%CI: 0.29–0.82). Most diet global cognitive benefits were observed to be associated with the preexisting higher consumption of rice, legumes, fresh vegetables, fresh fruit, meat, and nuts. In addition, the heterogeneity of associations between the consumption of certain foods and MCI subtypes was observed among Chinese adults aged over 55 years. These cross-sectional observations require validation in prospective studies.
The Effect of Colistin Treatment on the Selection of Colistin-Resistant Escherichia coli in Weaner Pigs

The treatment of diarrhea in the postweaning period is a common reason for the use of antimicrobials in pig production, and Escherichia coli is the single most important causative agent for this condition. Colistin has recently been classified as a critically important antimicrobial for human health, as it is a last-resort drug against certain multi-drug-resistant Gram-negative bacteria. Therefore, the use of colistin has been significantly reduced in some countries, including Denmark. Despite this, the drug is still commonly used to treat diarrhea in pigs in many countries, and there is a need to understand the risks associated with this practice. We performed a prospective cohort study to investigate the effect of colistin treatment on the changes in the average minimum inhibitory concentration (MIC) in commensal E. coli in a pig herd where no colistin-resistant bacteria were detectable before treatment. One group of pigs was batch treated with colistin after the clinical observation of diarrhea, one group was batch treated with colistin approximately 10 days before the expected onset of diarrhea, and a control group was not treated with colistin but provided with nonantimicrobial antidiarrheal feed supplement. Treatment with colistin in the dose and time combinations used did not result in a significant increase in the average colistin MIC values in E. coli. Moreover, no E. coli strains showed a MIC above the breakpoint of >2 mg/L against colistin. Co-selection of resistance to other antimicrobials was not observed.
Predicting Hospital Overall Quality Star Ratings in the USA

The U.S. Centers for Medicare and Medicaid Services (CMS) assigns quality star ratings to hospitals upon assessing their performance across 57 measures. Ratings can be used by healthcare consumers for hospital selection and hospitals for quality improvement. We provide a simpler, more intuitive modeling approach, aligned with recent criticism by stakeholders. An ordered logistic regression approach is proposed to assess associations between performance measures and ratings across eligible (n = 4519) U.S. hospitals. Covariate selection reduces the double counting of information from highly correlated measures. Multiple imputation allows for inference of star ratings when information on all measures is not available. Twenty performance measures were found to contain all the relevant information to formulate star rating predictions upon accounting for performance measure correlation. Hospitals can focus their efforts on a subset of model-identified measures, while healthcare consumers can predict quality star ratings for hospitals ineligible under CMS criteria.
Myelodysplasia Syndrome, Clonal Hematopoiesis and Cardiovascular Disease

Simple Summary The development of blood cancers is a complex process that involves the acquisition of specific blood disorders that precede cancer. These blood disorders are often driven by the accumulation of genetic abnormalities, which are discussed in this review. Likewise, predicting the rate of progression of these diseases is difficult, but it appears to be linked to which specific gene mutations are present in blood cells. In this review, we discuss a variety of genetic abnormalities that drive blood cancer, conditions that precede clinical symptoms of blood cancer, and how alterations in these genes change blood cell function. Additionally, we discuss the novel links between blood cancer development and heart disease. Abstract The development of myelodysplasia syndromes (MDS) is multiphasic and can be driven by a plethora of genetic mutations and/or abnormalities. MDS is characterized by a hematopoietic differentiation block, evidenced by increased immature hematopoietic cells, termed blast cells and decreased mature circulating leukocytes in at least one lineage (i.e., cytopenia). Clonal hematopoiesis of indeterminate potential (CHIP) is a recently described phenomenon preceding MDS development that is driven by somatic mutations in hemopoietic stem cells (HSCs). These mutant HSCs have a competitive advantage over healthy cells, resulting in an expansion of these clonal mutated leukocytes. In this review, we discuss the multiphasic development of MDS, the common mutations found in both MDS and CHIP, how a loss-of-function in these CHIP-related genes can alter HSC function and leukocyte development and the potential disease outcomes that can occur with dysfunctional HSCs. In particular, we discuss the novel connections between MDS development and cardiovascular disease.
NTRK Fusion Genes in Thyroid Carcinomas: Clinicopathological Characteristics and Their Impacts on Prognosis

Simple Summary NTRK fusion genes are important but not well studied molecular markers in thyroid cancer. Their identification could help improve diagnosis and prognosis, and determine appropriate treatment. The aims of this study were to identify NTRK fusion-positive thyroid tumors in a large cohort of different thyroid tumors, to characterize these tumors by molecular, clinical and pathological features and to evaluate the impact of NTRK-rearranged tumors on prognosis of the disease. A suitable approach for selective NTRK fusion gene testing in thyroid cancer samples was created and utilized. In a cohort of 59 NTRK-rearranged carcinomas, characteristic features were described and recommendations for surgery and prognostic factors were determined thanks to the long-term follow-up of patients. Abstract Chromosomal rearrangements of NTRK genes are oncogenic driver mutations in thyroid cancer (TC). This study aimed to identify NTRK fusion-positive thyroid tumors and to correlate them with clinical and pathological data and determine their prognostic significance. The cohort consisted of 989 different TC samples. Based on the detected mutation, samples were triaged, and those that were positive for a BRAF, HRAS, KRAS, NRAS, RET, RET/PTC or PAX8/PPARγ mutation were excluded from further analyses. NTRK fusion gene testing was performed in 259 cases, including 126 cases using next-generation sequencing. NTRK fusion genes were detected in 57 of 846 (6.7%) papillary thyroid carcinomas and in 2 of 10 (20.0%) poorly differentiated thyroid carcinomas. A total of eight types of NTRK fusions were found, including ETV6/NTRK3, EML4/NTRK3, RBPMS/NTRK3, SQSTM1/NTRK3, TPM3/NTRK1, IRF2BP2/NTRK1, SQSTM1/NTRK1 and TPR/NTRK1. NTRK fusion-positive carcinomas were associated with the follicular growth pattern, chronic lymphocytic thyroiditis and lymph node metastases. NTRK1-rearranged carcinomas showed a higher frequency of multifocality and aggressivity than NTRK3-rearranged carcinomas. Tumor size, presence of metastases, positivity for the NTRK3 or NTRK1 fusion gene and a late mutation event (TERT or TP53 mutation) were determined as factors affecting patient prognosis. NTRK fusion genes are valuable diagnostic and prognostic markers.
Assessment of Gait after Treatment of Tibial Nonunion with the Ilizarov Method

Background: Tibial nonunion is a common bone union disorder leading to abnormal gait, and thus reducing quality of life in the social dimension. Research question: The aim of our work was to comprehensively assess gait parameters of patients who had undergone Ilizarov treatment for tibial nonunion compared to a control group of healthy individuals. Methods: This study evaluated patients treated for aseptic tibial nonunion with the Ilizarov method. 24 patients with a mean age of 55.0 years were included in the study. The control group consisted of 32 healthy volunteers with no significant medical history who were selected to match the gender and age of patients in the study group so that the groups were homogeneous. A Zebris Medical GmbH pedobarographic platform was used to assess the gait parameters. Results: For all gait parameters examined, force forefoot max, force backfoot max, step length, stance phase, swing phase and step time, we observed statistically significant differences between the group that had undergone treatment and the control group. In the group of patients, statistically significant differences between the operated lower limb and the non-operated limb were only observed for the force forefoot max and step time parameters (p = 0.029 and p = 0.045, respectively). Patients presented a longer loading of the operated limb (0.720 s) than the non-operated limb (0.635 s). For the stride time, step cadence and gait velocity parameters, healthy subjects achieved much better results during locomotion, and these differences were statistically significant at p < 0.001. Significance: Treatment of tibial nonunion with the Ilizarov method did not restore normal gait parameters in our group of patients. In fact, the gait parameters of patients were significantly worse than the healthy individuals in the control group. Furthermore, gait parameters following treatment were not symmetrical, and the dynamics of the musculoskeletal system remained impaired.
Dual Role for Astroglial Copper-Assisted Polyamine Metabolism during Intense Network Activity

Astrocytes serve essential roles in human brain function and diseases. Growing evidence indicates that astrocytes are central players of the feedback modulation of excitatory Glu signalling during epileptiform activity via Glu-GABA exchange. The underlying mechanism results in the increase of tonic inhibition by reverse operation of the astroglial GABA transporter, induced by Glu-Na+ symport. GABA, released from astrocytes, is synthesized from the polyamine (PA) putrescine and this process involves copper amino oxidase. Through this pathway, putrescine can be considered as an important source of inhibitory signaling that counterbalances epileptic discharges. Putrescine, however, is also a precursor for spermine that is known to enhance gap junction channel communication and, consequently, supports long-range Ca2+ signaling and contributes to spreading of excitatory activity through the astrocytic syncytium. Recently, we presented the possibility of neuron-glia redox coupling through copper (Cu+/Cu2+) signaling and oxidative putrescine catabolism. In the current work, we explore whether the Cu+/Cu2+ homeostasis is involved in astrocytic control on neuronal excitability by regulating PA catabolism. We provide supporting experimental data underlying this hypothesis. We show that the blockade of copper transporter (CTR1) by AgNO3 (3.6 µM) prevents GABA transporter-mediated tonic inhibitory currents, indicating causal relationship between copper (Cu+/Cu2+) uptake and the catabolism of putrescine to GABA in astrocytes. In addition, we show that MnCl2 (20 μM), an inhibitor of the divalent metal transporter DMT1, also prevents the astrocytic Glu-GABA exchange. Furthermore, we observed that facilitation of copper uptake by added CuCl2 (2 µM) boosts tonic inhibitory currents. These findings corroborate the hypothesis that modulation of neuron-glia coupling by copper uptake drives putrescine → GABA transformation, which leads to subsequent Glu-GABA exchange and tonic inhibition. Findings may in turn highlight the potential role of copper signaling in fine-tuning the activity of the tripartite synapse.
Associations between Pre-Bariatric High-Sensitivity C-Reactive Protein and Post-Surgery Outcomes

Background: Obesity is a chronic inflammatory condition associated with increased circulating levels of C-reactive protein (CRP). Bariatric surgery has been reported to be effective in improving both inflammatory and liver status. Our aims were to elucidate the relationships between pre-surgery high sensitivity-CRP (hs-CRP) values and post-surgery weight loss and liver steatosis and fibrosis in patients with severe obesity undergoing Roux-en-Y gastric bypass. Methods: We conducted an observational prospective study on 90 individuals with morbid obesity, who underwent gastric bypass. Anthropometric indices, laboratory assessment (lipid panel, glycemic status, liver enzymes, and hs-CRP), liver stiffness and steatosis were evaluated at baseline and 6-months after surgery. Results: There was a significant post-surgery reduction in all the anthropometric variables, with an average weight loss of 33.93 ± 11.79 kg; the mean percentage of total weight loss (TWL) was 27.96 ± 6.43%. Liver elasticity was significantly reduced (from 6.1 ± 1.25 to 5.42 ± 1.52 kPa; p = 0.002), as well as liver aminotransferases, nonalcoholic fatty liver disease fibrosis score (NFS) and the grade of steatosis. Serum hs-CRP levels significantly reduced (from 9.26 ± 8.45 to 3.29 ± 4.41 mg/L; p < 0.001). The correlations between hs-CRP levels and liver fibrosis (elastography), steatosis (ultrasonography), fibrosis-4 index, NFS, and surgery success rate were not significant. Regression analyses showed that serum hs-CRP levels were not predictive of liver status and success rate after surgery in both unadjusted and adjusted models. Conclusions: In patients with morbid obesity, bariatric surgery caused a significant decrease in hs-CRP levels, liver stiffness and steatosis. Baseline hs-CRP values did not predict the weight-loss success rate and post-surgery liver status.
Increased Creatine Kinase May Predict A Worse COVID-19 Outcome

Early reports from Asia suggested that increased serum levels of the muscular enzyme creatine-(phospho)-kinase (CK/CPK) could be associated with a more severe prognosis in COVID-19. The aim of this single-center retrospective cohort study of 331 consecutive COVID-19 patients who were hospitalized during Italy’s “first wave” was to verify this relationship, and to evaluate the role of possible confounding factors (age, body mass index, gender, and comorbidities). We subdivided our cohort in two groups, based on “severe” (n = 99) or “mild” (n = 232) outcomes. “Severe” disease is defined here as death and/or mechanical invasive ventilation, in contrast to “mild” patients, who were discharged alive with no need for invasive ventilation; this latter group could also include those patients who were treated with non-invasive ventilation. The CK levels at admission were higher in those subjects who later experienced more severe outcomes (median, 126; range, 10–1672 U/L, versus median, 82; range, 12–1499 U/L, p = 0.01), and hyperCKemia >200 U/L was associated with a worse prognosis. Regression analysis confirmed that increased CK acted as an independent predictor for a “severe” outcome. HyperCKemia was generally transient, returning to normal during hospitalization in the majority of both “severe” and “mild” patients. Although the direct infection of voluntary muscle is unproven, transient muscular dysfunction is common during the course of COVID-19. The influence of this novel coronavirus on voluntary muscle really needs to be clarified.
Natural Product Gene Clusters in the Filamentous Nostocales Cyanobacterium HT-58-2

Cyanobacteria are known as rich repositories of natural products. One cyanobacterial-microbial consortium (isolate HT-58-2) is known to produce two fundamentally new classes of natural products: the tetrapyrrole pigments tolyporphins A–R, and the diterpenoid compounds tolypodiol, 6-deoxytolypodiol, and 11-hydroxytolypodiol. The genome (7.85 Mbp) of the Nostocales cyanobacterium HT-58-2 was annotated previously for tetrapyrrole biosynthesis genes, which led to the identification of a putative biosynthetic gene cluster (BGC) for tolyporphins. Here, bioinformatics tools have been employed to annotate the genome more broadly in an effort to identify pathways for the biosynthesis of tolypodiols as well as other natural products. A putative BGC (15 genes) for tolypodiols has been identified. Four BGCs have been identified for the biosynthesis of other natural products. Two BGCs related to nitrogen fixation may be relevant, given the association of nitrogen stress with production of tolyporphins. The results point to the rich biosynthetic capacity of the HT-58-2 cyanobacterium beyond the production of tolyporphins and tolypodiols.
Role of heat-shock proteins in infection of human adenocarcinoma cell line MCF-7 by tumor-adapted rotavirus isolates

Abstract Background: Viruses are being used as alternative and complementary tools for treating cancers. Oncolytic viruses exhibit tumor tropism, ability to enhance anti-tumor immunity and ability to be used in combination with conventional chemotherapy and radiotherapy. We have recently selected some rotavirus isolates which are adapted to efficiently infect and kill tumor cell lines. Aim: We tested five tumor cell-adapted rotavirus isolates for their ability to infect the human adenocarcinoma cell line MCF-7. Methods: Cell surface membrane-associated proteins mediating virus particle attachment were characterized using ELISA, immunoprecipitation, FACS analysis, and antibody blocking. Results: It was found that heat shock proteins (HSPs) such as Hsp90, Hsp70, Hsp60, and Hsp40 are expressed on the cell surface forming complexes with protein disulfide isomerase (PDI), integrin β3, and heat shock cognate protein 70 (Hsc70) in lipid raft microdomains. Interaction of rotavirus isolates with these cellular proteins was further confirmed by a competition assay and an inhibition assay involving the HSPs tested. Conclusion: Our findings suggest that the tumor cell-adapted rotavirus isolates studied here offer a promising tool for killing tumor cells, thus encouraging further research into this topic, including animal models.