Miracle-dz/UniFAR-FTUs huggingface dataset:
Copper/Zinc Superoxide Dismutase from the Crocodile Icefish Chionodraco hamatus: Antioxidant Defense at Constant Sub-Zero Temperature

In the present study, we describe the purification and molecular characterization of Cu,Zn superoxide dismutase (SOD) from Chionodraco hamatus, an Antarctic teleost widely distributed in many areas of the Ross Sea that plays a pivotal role in the Antarctic food chain. The primary sequence was obtained using biochemical and molecular biology approaches and compared with Cu,Zn SODs from other organisms. Multiple sequence alignment using the amino acid sequence revealed that Cu,Zn SOD showed considerable sequence similarity with its orthologues from various vertebrate species, but also some specific substitutions directly linked to cold adaptation. Phylogenetic analyses presented the monophyletic status of Antartic Teleostei among the Perciformes, confirming the erratic differentiation of these proteins and concurring with the theory of the “unclock-like” behavior of Cu,Zn SOD evolution. Expression of C. hamatus Cu,Zn SOD at both the mRNA and protein levels were analyzed in various tissues, highlighting the regulation of gene expression related to environmental stress conditions and also animal physiology. The data presented are the first on the antioxidant enzymes of a fish belonging to the Channichthyidae family and represent an important starting point in understanding the antioxidant systems of these organisms that are subject to constant risk of oxidative stress.
ARNT‐dependent CCR8 reprogrammed LDH isoform expression correlates with poor clinical outcomes of prostate cancer

Lactate dehydrogenase isozyme (LDH) is a tetramer constituted of two isoforms, LDHA and LDHB, the expression of which is associated with cell metabolism and cancer progression. Our previous study reveals that CC‐chemokine ligand‐18 (CCL18) is involved in progression of prostate cancer (PCa). This study aims to investigate how CCL18 regulates LDH isoform expression, and therefore, contributes to PCa progression. The data revealed that the expression of LDHA was upregulated and LDHB was downregulated in PCa cells by CCL18 at both messenger RNA and protein levels. The depletion of CCR8 reduced the ability of CCL18 to promote the proliferation, migration, and lactate production of PCa cells. Depletion of a CCR8 regulated transcription factor, ARNT, significantly reduced the expression of LDHA. In addition, The Cancer Genome Atlas dataset analyses revealed a positive correlation between CCR8 and ARNT expression. Two dimension difference gel electrophoresis revealed that the LDHA/LDHB ratio was increased in the prostatic fluid of patients with PCa and PCa tissues. Furthermore, increased LDHA/LDHB ratio was associated with poor clinical outcomes of patients with PCa. Together, our results indicate that the CCR8 pathway programs LDH isoform expression in an ARNT dependent manner and that the ratio of LDHA/LDHB has the potential to serve as biomarkers for PCa diagnosis and prognosis.
Muscle swelling following blood flow‐restricted exercise does not differ between cuff widths in the proximal or distal portions of the upper leg

The purpose was to understand how wider cuffs, covering larger portions of the limb, may affect acute muscle swelling when used during low‐load knee extension exercise with blood flow restriction. A total of 96 individuals (53 females and 43 males) completed two visits, with visit one used for measuring maximal strength and arterial occlusion pressure (AOP), and visit two to compare between a narrow (5 cm) and a wide (12 cm) cuff for acute changes in muscle thickness and echo intensity following exercise. Ultrasound measurements were completed at a proximal and distal site within both legs, with the proximal site located beneath the cuff within the leg exercising using the wide cuff. Study findings indicate that the difference in acute changes for muscle thickness [median difference (95% credible interval) of 0.009 (−0.03, 0.05) cm] and echo intensity [median difference (95% credible interval) of 0.79 (−0.28, 1.89) AU] between cuff widths did not differ between proximal and distal sites. Additionally, acute changes in muscle thickness did not differ between cuff widths, sexes or participants who had AOP measured and those who were estimated. Lastly, acute changes in echo intensity did not differ between cuff widths and those who had AOP measured and those who were estimated. However, there was evidence showing how there might be greater reductions in echo intensity for females at the distal site. The previously observed attenuation of muscle growth under the cuff is unlikely to be related to differences in the acute muscle swelling response.
Examination of Nonlinear and Functional Mixed-Effects Models with Nonparametrically Generated Data

Abstract Previous research has shown functional mixed-effects models and traditional mixed-effects models perform similarly when recovering individual trajectories when data were generated following a parametric structure. We extend this previous work and compare nonlinear mixed-effects (NMEM) and functional mixed-effects models’ (FMEM) ability to recover underlying trajectories when generated from an inherently nonparametric process. Nonlinear trajectories were generated using B-splines, NMEMs and FMEMs were estimated, and the accuracy of the estimated curves was examined. Sample size, number of time points per curve, and measurement design were varied across simulation conditions. Results showed the FMEMs recovered the underlying mean curve more accurately than the NMEMs, and that, the FMEMs tended to recover the underlying individual curves more accurately than the NMEMs. Progesterone cycle data were then analyzed to demonstrate the utility of both approaches, and models performed similarly when analyzing these data.
Metagenomic analysis of historical herbarium specimens reveals a postmortem microbial community

Advances in DNA extraction and next‐generation sequencing have made a vast number of historical herbarium specimens available for genomic investigation. These specimens contain not only genomic information from the individual plants themselves, but also from associated microorganisms such as bacteria and fungi. These microorganisms may have colonized the living plant (e.g., pathogens or host‐associated commensal taxa) or may result from postmortem colonization that may include decomposition processes or contamination during sample handling. Here we characterize the metagenomic profile from shotgun sequencing data from herbarium specimens of two widespread plant species (Ambrosia artemisiifolia and Arabidopsis thaliana) collected up to 180 years ago. We used blast searching in combination with megan and were able to infer the metagenomic community even from the oldest herbarium sample. Through comparison with contemporary plant collections, we identify three microbial species that are nearly exclusive to herbarium specimens, including the fungus Alternaria alternata, which can comprise up to 7% of the total sequencing reads. This species probably colonizes the herbarium specimens during preparation for mounting or during storage. By removing the probable contaminating taxa, we observe a temporal shift in the metagenomic composition of the invasive weed Am. artemisiifolia. Our findings demonstrate that it is generally possible to use herbarium specimens for metagenomic analyses, but that the results should be treated with caution, as some of the identified species may be herbarium contaminants rather than representing the natural metagenomic community of the host plant.
Adjunctive effect of mouthrinse on treatment of peri‐implant mucositis using mechanical debridement: A randomized clinical trial

Abstract Aim To study effect of delmopinol hydrochloride (DEL) in comparison with chlorhexidine digluconate (CHX) and a placebo (PLA) in addition to non‐surgical mechanical debridement in patients with peri‐implant mucositis. Materials and methods Eighty‐nine patients with at least one implant diagnosed with peri‐implant mucositis were randomly assigned to one of three study groups (DEL, CHX and PLA). Professional non‐surgical mechanical debridement was performed at baseline. Mouth rinsing was carried out by the patients twice a day in addition to their regular oral hygiene practices. Assessments of efficacy were performed for the primary outcome ‐ Implant bleeding on probing (IBOP%) and secondary outcomes ‐ modified Bleeding Index (mBI) and modified Plaque Index (mPI) at 1 and 3 months. Results At 3 months, there was statistically significant reduction in IBOP% and mBI within the study groups compared to baseline. However, there was no statistically significant difference between the study groups at 3 months follow‐up. Moreover, there was a statistically significant difference according to mPI at 1 month between the chlorhexidine and placebo group (p = .004). Conclusions This study confirms that mechanical debridement combined with oral hygiene instruction is effective in treatment of peri‐implant mucositis. The clinical effects between groups were comparable.
Outpatient decolonization after recurrent skin infection with Panton-Valentine leukocidin (PVL)-producing S. aureus—The importance of treatment repetition

Background Recurrent skin abscesses are often associated with Panton-Valentine leukocidin-producing strains of S. aureus (PVL-SA). Decolonization measures are required along with treatment of active infections to prevent re-infection and spreading. Even though most PVL-SA patients are treated as outpatients, there are few studies that assess the effectiveness of outpatient topical decolonization in PVL-SA patients. Methods We assessed the results of topical decolonization of PVL-SA in a retrospective review of patient files and personal interviews. Successful decolonization was defined as the absence of any skin abscesses for at least 6 months after completion of the final decolonization treatment. Clinical and demographic data was assessed. An intention-to-treat protocol was used. Results Our cohort consisted of 115 symptomatic patients, 66% from PVL-positive MSSA and 19% from PVL-positive MRSA. The remaining 16% consisted of symptomatic patients with close contact to PVL-SA positive index patients but without detection of PVL-SA. The majority of patients were female (66%). The median age was 29.87% of the patients lived in multiple person households. Our results showed a 48% reduction in symptomatic PVL-SA cases after the first decolonization treatment. The results also showed that the decrease continued with each repeated decolonization treatment and reached 89% following the 5th treatment. A built multivariable Cox proportional-hazards model showed that the absence of PVL-SA detection (OR 2.0) and living in single person households (OR 2.4) were associated with an independently increased chance of successful decolonization. Conclusion In our cohort, topical decolonization was a successful preventive measure for reducing the risk of PVL-SA skin abscesses in the outpatient setting. Special attention should be given to patients living in multiple person households because these settings could confer a risk that decolonization will not be successful.
Gas Plasma-Treated Prostate Cancer Cells Augment Myeloid Cell Activity and Cytotoxicity

Despite recent improvements in cancer treatment, with many of them being related to foster antitumor immunity, tumor-related deaths continue to be high. Novel avenues are needed to complement existing therapeutic strategies in oncology. Medical gas plasma technology recently gained attention due to its antitumor activity. Gas plasmas act via the local deposition of a plethora of reactive oxygen species (ROS) that promote the oxidative cancer cell death. The immunological consequences of plasma-mediated tumor cell death are only poorly understood, however. To this end, we exposed two prostate cancer cell lines (LNCaP, PC3) to gas plasma in vitro, and investigated the immunomodulatory effects of the supernatants in as well as of direct co-culturing with two human myeloid cell lines (THP-1, HL-60). After identifying the cytotoxic action of the kINPen plasma jet, the supernatants of plasma-treated prostate cancer cells modulated myeloid cell-related mitochondrial ROS production and their metabolic activity, proliferation, surface marker expression, and cytokine release. Direct co-culture amplified differentiation-like surface marker expression in myeloid cells and promoted their antitumor-toxicity in the gas plasma over the untreated control conditions. The results suggest that gas plasma-derived ROS not only promote prostate cancer cell death but also augment myeloid cell activity and cytotoxicity.
Glycemic impact of intensified self monitoring of blood glucose in insulin treated subjects with type 2 diabetes mellitus

Objective:The aim of this study was to evaluate if intensified self-monitoring of blood glucose (SMBG) improves glycemic control in insulin-treated subjects with type 2 diabetes mellitus (T2DM). Methods:Ninety-six adults with stable but poorly controlled [glycated hemoglobin (HbA1c) level >7.5%] T2DM receiving twice-daily biphasic insulin were randomly assigned to either of the two groups: intensive monitors (IM) that performed SMBG at least twice daily or conventional monitors (CM) that performed SMBG at their discretionary frequency for 12 weeks. Demographic, clinical, and glycemic indices, including fasting blood glucose (FBG), postprandial glucose (PPG), and HbA1c, were compared at baseline and week 12. Results:A total of 71 subjects (25 IM and 46 CM) completed the study. Both groups had similar HbA1c at baseline. From baseline to week 12, the IM group had higher mean daily test strip usage (P <0.001), engaged in more frequent insulin dose adjustments (P <0.001), and attained greater daily insulin dosage (P = 0.002). All glycemic indices including FBG, PPG, and HbA1c improved significantly from baseline to week 12 in the IM but not in the CM group. HbA1c level declined by −1.2 ±0.4% in the IM group (P = 0.002). There was no difference in the frequency of hypoglycemia in both groups. The monthly cost of intensified SMBG was nearly four times that of conventional monitoring (P <0.001). Conclusion:Both short- and long-term glycemic control significantly improved by intensified SMBG in stable but poorly controlled insulin-treated adults with T2DM. Intensified SMBG enabled better self-titration of insulin and probably other self-care practices. This benefit, however, occurred at the expense of costs that may be difficult to sustain in resource-poor countries.
Treatment of infantile spasms: why do we know so little?

ABSTRACT Introduction Infantile spasm (IS) is an epileptic syndrome with typical onset within the first 2 years of life. This condition might be caused by several etiologies. IS is associated with pathological neuronal networks; however, definite hypotheses on neurobiological processes are awaited. Areas covered Changes in NMDA and GABAB receptors and increase of Ca2+ conductance are some of the possible pathophysiological mechanisms. Animal models can help, but most have only some features of IS. Outcome is strongly affected by etiology and the timing of treatment, which relies still on ACTH, oral steroids, and vigabatrin. No significant differences in terms of efficacy have been documented, though a combination of ACTH and vigabatrin seems to be associated with better long-term outcomes. Despite the increasing knowledge about the etiology and pathophysiology of IS, in the last years, no new treatment approaches have been recognized to be able to modify the neurobiological process underlying IS. Precision medicine has far to come in IS. Expert opinion Recently, no new therapeutic options for IS have emerged, probably due to the lack of reliable animal models and to the extreme variability in etiologies. Consequently, the outlook for patients and families is poor and early recognition and intervention remain research priorities.
Compartmentalization of adenosine metabolism in cancer cells and its modulation during acute hypoxia

ABSTRACT Extracellular adenosine mediates diverse anti-inflammatory, angiogenic and vasoactive effects, and has become an important therapeutic target for cancer, which has been translated into clinical trials. This study was designed to comprehensively assess adenosine metabolism in prostate and breast cancer cells. We identified cellular adenosine turnover as a complex cascade, comprising (1) the ectoenzymatic breakdown of ATP via sequential ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1, officially known as ENPP1), ecto-5′-nucleotidase (CD73, also known as NT5E), and adenosine deaminase reactions, and ATP re-synthesis through a counteracting adenylate kinase and members of the nucleoside diphosphate kinase (NDPK, also known as NME/NM23) family; (2) the uptake of nucleotide-derived adenosine via equilibrative nucleoside transporters; and (3) the intracellular adenosine phosphorylation into ATP by adenosine kinase and other nucleotide kinases. The exposure of cancer cells to 1% O2 for 24 h triggered an ∼2-fold upregulation of CD73, without affecting nucleoside transporters, adenosine kinase activity and cellular ATP content. The ability of adenosine to inhibit the tumor-initiating potential of breast cancer cells via a receptor-independent mechanism was confirmed in vivo using a xenograft mouse model. The existence of redundant pathways controlling extracellular and intracellular adenosine provides a sufficient justification for reexamination of the current concepts of cellular purine homeostasis and signaling in cancer. This article has an associated First Person interview with the first author of the paper. Summary: The identification of redundant pathways that tightly control cellular ATP and adenosine levels provides novel insights into the purinergic mechanisms governing cancer cell metabolism and signaling.
Kidney function and glucose metabolism in overweight and obese cats

Abstract Background In people, obesity and prediabetes mellitus might predispose to chronic kidney disease (CKD). Aims To assess the association of overweight [Body condition score (BCS) >5] and glucose metabolism alterations, with established or potential markers of CKD. In addition, fructosamine and fasted blood glucose were compared as predictors of early abnormal glucose metabolism. Methods 54 clinically healthy cats were included in a cross-sectional study comprising 25 neutered males and 29 (28 neutered) females aged 7.2 (5.5–9.4) years. Two potential markers of CKD, namely urinary free active transforming growth factor-β1-creatinine ratio and urinary retinol binding protein-creatinine ratio were measured along with other parameters to assess CKD. A receiver operating curve was used to identify the best sensitivity and specificity of fructosamine to identify cats with fasting glucose >6.5 mmol/L. Results No association was found between BCS and markers of CKD. Fructosamine was greater in cats with fasting glucose >6.5 mmol/L compared to those with fasting glucose ≤6.5 mmol/L. A fructosamine concentration ≥250 µmol/L was able to detect cats with hyperglycemia with a sensitivity of 77% and a specificity of 65%. Furthermore, fructosamine was more strongly correlated with fasting glucose than albumin-corrected fructosamine (r = 0.43, p = 0.002 vs r = 0.32, p = 0.026). Cats with higher fructosamine had lower serum symmetric dimethylarginine concentrations. Conclusion The present study does not suggest an effect of obesity on renal function in domestic cats. Clinical relevance Fructosamine might be of value for the diagnosis of prediabetes mellitus in cats.
Sympatho–Vagal Dysfunction in Patients with End-Stage Lung Disease Awaiting Lung Transplantation

Although the literature demonstrates that cardiac autonomic control (CAC) might be impaired in patients with chronic pulmonary diseases, the interplay between CAC and disease severity in end-stage lung disease has not been studied yet. We investigated the effects of end-stage lung disease on CAC through the analysis of heart rate variability (HRV) among patients awaiting lung transplantation. Forty-nine patients on the waiting list for lung transplantation (LTx; 19 men, age 38 ± 15 years) and 49 healthy non-smoking controls (HC; 22 men, age 40 ± 16 years) were enrolled in a case–control study at Policlinico Hospital in Milan, Italy. LTx patients were divided into two groups, according to disease severity evaluated by the Lung Allocation Score (LAS). To assess CAC, electrocardiogram (ECG) and respiration were recorded at rest for 10 min in supine position and for 10 min during active standing. Spectral analysis identified low and high frequencies (LF, sympathetic, and HF, vagal). Symbolic analysis identified three patterns, i.e., 0V% (sympathetic) and 2UV% and 2LV% (vagal). Compared to HCs, LTx patients showed higher markers of sympathetic modulation and lower markers of vagal modulation. However, more severely affected LTx patients, compared to less severely affected ones, showed an autonomic profile characterized by loss of sympathetic modulation and predominant vagal modulation. This pattern can be due to a loss of sympathetic rhythmic oscillation and a subsequent prevalent respiratory modulation of heart rate in severely affected patients.
Endothelial Hyper-Permeability Induced by T1D Sera Can be Reversed by iNOS Inactivation

Type 1 Diabetes Mellitus (T1D) is associated with accelerated atherosclerosis that is responsible for high morbidity and mortality. Endothelial hyperpermeability, a feature of endothelial dysfunction, is an early step of atherogenesis since it favours intimal lipid uptake. Therefore, we tested endothelial leakage by loading the sera from T1D patients onto cultured human endothelial cells and found it increased by hyperglycaemic sera. These results were phenocopied in endothelial cells cultured in a medium containing high concentrations of glucose, which activates inducible nitric oxide synthase with a consequent increase of nitric oxide. Inhibition of the enzyme prevented high glucose-induced hyperpermeability, thus pointing to nitric oxide as the mediator involved in altering the endothelial barrier function. Since nitric oxide is much higher in sera from hyperglycaemic than normoglycaemic T1D patients, and the inhibition of inducible nitric oxide synthase prevents sera-dependent increased endothelial permeability, this enzyme might represent a promising biochemical marker to be monitored in T1D patients to predict alterations of the vascular wall, eventually promoting intimal lipid accumulation.