Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNA Profile and Adaptive Response to Exercise Training: A Review

Abstract MicroRNAs are small non-coding regulatory RNAs which may be released into the systemic circulation as a consequence of the body's adaptation to exercise. The expression profile of circulating miRNAs (ci-miRNAs) has been proposed as a potential diagnostic biomarker for adaptive responses of particular systems to physical exertion. Several miRNAs are recognized as regulators of signalling pathways such as the IGF1/PI3K/AKT/mTOR axis, relevant to exercise adaptation. MicroRNA levels may fluctuate depending on training type/exercise regimen in correlation with phenotypic features such as VO2 max. Muscle-specific miRNAs have been proposed as regulators of skeletal muscle/myocardial interactions during physical exertion, thereby facilitating adaptation. Differential expression of miRNAs may relate to molecular patterns of communication triggered during/after exercise as response, recovery and adaptation mechanisms to training load. This review highlights recent findings and the potential significance of specific miRNAs in the process of exercise adaptation. Altered ci-miRNA profiles following exercise suggest that they may be useful biomarkers of health and adaptation to intervention strategies. Identification of the concert of miRNA expression signatures together with their targets is critical towards understanding gene regulation in this context. Understanding how the external environment influences gene expression via miRNAs will provide insight into potential therapeutic target strategies for disease.
Chlorophyllin e6-mediated photodynamic therapy inhibits proliferation and induces apoptosis in human bladder cancer cells

Patients with non-muscle invasive bladder cancer (NMIBC) frequently relapse following surgery due to incomplete resection and chemoresistance, highlighting the importance of developing novel therapeutic strategies that mechanistically assist in eradicating the residual tumor. The aim of the present study was to evaluate the anticancer effect of chlorophyllin e6-mediated photodynamic therapy (e6-PDT) and its potential mechanisms by using monolayer cells or multicellular tumor spheroid models of human bladder cancer cells (T24 and 5637). The results revealed that e6-PDT exhibited significant cytotoxicity in the T24 and 5637 cells of these two models as detected by the Water-Soluble Tetrazolium Salts-1 and CellTiter-Glo Luminescent Cell Viability assays, respectively. Cell migration and invasion capacities decreased markedly following e6-PDT. In addition, the cells following e6-PDT exhibited typical morphological changes of apoptosis as detected by fluorescence microscopy with 4′,6-diamidino-2-phenylindole staining and transmission electron microscopy. A greater number of apoptotic cells were observed post-e6-PDT by flow cytometry. The expression levels of poly(adenosine diphosphate-ribose) polymerase (PARP) and B-cell lymphoma 2 protein were decreased, while cleaved PARP was increased, significantly following e6-PDT as determined by western blotting. The level of intracellular reactive oxygen species (ROS) was increased, while the activity of superoxide dismutase (SOD) was decreased, significantly in e6-PDT-treated cells. Thus, the novel e6-PDT exhibits prominent photo-cytotoxicity effect and the induction of apoptosis was probably due to the inhibition of SOD activity and the generation of ROS. These results indicate that chlorophyllin e6 is an effective photosensitizer and that e6-PDT may have a therapeutic application for the treatment of bladder cancer.
Testosterone Administration after Traumatic Brain Injury Reduces Mitochondrial Dysfunction and Neurodegeneration.

Traumatic brain injury (TBI) increases Ca2+ influx into neurons and desynchronizes mitochondrial function leading to energy depletion and apoptosis. This process may be influenced by brain testosterone (TS) levels, which are known to decrease after TBI. We hypothesized that a TS-based therapy could preserve mitochondrial neuroenergetics after TBI, thereby reducing neurodegeneration. C57BL/6J mice were submitted to sham treatment or severe parasagittal controlled cortical impact (CCI) and were subcutaneously injected with either vehicle (VEH-SHAM and VEH-CCI) or testosterone cypionate (15 mg/kg, TS-CCI) for 10 days. Cortical tissue homogenates ipsilateral to injury were used for neurochemical analysis. The VEH-CCI group displayed an increased Ca2+-induced mitochondrial swelling after the addition of metabolic substrates (pyruvate, malate, glutamate, succinate, and adenosine diphosphate [PMGSA]). The addition of Na+ stimulated mitochondrial Ca2+ extrusion through Na+/Ca2+/Li+ exchanger (NCLX) in VEH-SHAM and TS-CCI, but not in the VEH-CCI group. Reduction in Ca2+ efflux post-injury was associated with impaired mitochondrial membrane potential formation/dissipation, and decreased mitochondrial adenosine triphosphate (ATP)-synthase coupling efficiency. Corroborating evidence of mitochondrial uncoupling was observed with an increase in H2O2 production post-injury, but not in superoxide dismutase (SOD2) protein levels. TS administration significantly reduced these neuroenergetic alterations. At molecular level, TS prevented the increase in pTauSer396 and alpha-Spectrin fragmentation by the Ca2+dependent calpain-2 activation, and decreased both caspase-3 activation and Bax/BCL-2 ratio, which suggests a downregulation of mitochondrial apoptotic signals. Search Tool for the Retrieval of Interacting Genes/Proteins database provided two distinct gene/protein clusters, "upregulated and downregulated," interconnected through SOD2. Therefore, TS administration after a severe CCI improves the mitochondrial Ca2+extrusion through NCLX exchanger and ATP synthesis efficiency, ultimately downregulating the overexpression of molecular drivers of neurodegeneration.
Whole-genome analysis of extraintestinal Escherichia coli sequence type 73 from a single hospital over a 2 year period identified different circulating clonal groups

Sequence type (ST)73 has emerged as one of the most frequently isolated extraintestinal pathogenic Escherichia coli. To examine the localized diversity of ST73 clonal groups, including their mobile genetic element profile, we sequenced the genomes of 16 multiple-drug resistant ST73 isolates from patients with urinary tract infection from a single hospital in Sydney, Australia, between 2009 and 2011. Genome sequences were used to generate a SNP-based phylogenetic tree to determine the relationship of these isolates in a global context with ST73 sequences (n=210) from public databases. There was no evidence of a dominant outbreak strain of ST73 in patients from this hospital, rather we identified at least eight separate groups, several of which reoccurred, over a 2 year period. The inferred phylogeny of all ST73 strains (n=226) including the ST73 clone D i2 reference genome shows high bootstrap support and clusters into four major groups that correlate with serotype. The Sydney ST73 strains carry a wide variety of virulence-associated genes, but the presence of iss, pic and several iron-acquisition operons was notable.
A CASPR1–ATP1B3 protein interaction modulates plasma membrane localization of Na+/K+-ATPase in brain microvascular endothelial cells

Contactin-associated protein 1 (CASPR1 or CNTNAP1) was recently reported to be expressed in brain microvascular endothelial cells (BMECs), the major component of the blood–brain barrier. To investigate CASPR1's physiological role in BMECs, here we used CASPR1 as a bait in a yeast two-hybrid screen to identify CASPR1-interacting proteins and identified the β3 subunit of Na+/K+-ATPase (ATP1B3) as a CASPR1-binding protein. Using recombinant and purified CASPR1, RNAi, GST-pulldown, immunofluorescence, immunoprecipitation, and Na+/K+-ATPase activity assays, we found that ATP1B3's core proteins, but not its glycosylated forms, interact with CASPR1, which was primarily located in the endoplasmic reticulum of BMECs. CASPR1 knockdown reduced ATP1B3 glycosylation and prevented its plasma membrane localization, phenotypes that were reversed by expression of full-length CASPR1. We also found that the CASPR1 knockdown reduces the plasma membrane distribution of the α1 subunit of Na+/K+-ATPase, which is the major component assembled with ATP1B3 in the complete Na+/K+-ATPase complex. The binding of CASPR1 with ATP1B3, but not the α1 subunit, indicated that CASPR1 binds with ATP1B3 to facilitate the assembly of Na+/K+-ATPase. Furthermore, the activity of Na+/K+-ATPase was reduced in CASPR1-silenced BMECs. Interestingly, shRNA-mediated CASPR1 silencing reduced glutamate efflux through the BMECs. These results demonstrate that CASPR1 binds with ATP1B3 and thereby contributes to the regulation of Na+/K+-ATPase maturation and trafficking to the plasma membrane in BMECs. We conclude that CASPR1-mediated regulation of Na+/K+-ATPase activity is important for glutamate transport across the blood–brain barrier.
Simulation of Field Assisted Sintering of Silicon Germanium Alloys

We report a numerical study of the field assisted sintering of silicon germanium alloys by a finite element method, which takes into account contact resistances, thermal expansion and the thermoelectric effect. The distribution of electrical and thermal fields was analyzed numerically, based on the experimental data collected from spark plasma sintering (SPS) apparatus. The thermoelectric properties of Si-Ge used within the simulation were considered as the function of density and the sintering temperature. Quantitative estimation of the temperature distribution during the sintering pointed to a significant, up to 60 °C, temperature difference within the specimen volume for the case of the sintering temperature at 1150 °C.
Sugar-Sweetened Beverage Consumption 3 Years After the Berkeley, California, Sugar-Sweetened Beverage Tax

Objectives To estimate changes in sugar-sweetened beverage (SSB) and water consumption 3 years after an SSB tax in Berkeley, California, relative to unexposed comparison neighborhoods. Methods Data came from repeated annual cross-sectional beverage frequency questionnaires from 2014 to 2017 in demographically diverse Berkeley (n = 1513) and comparison (San Francisco and Oakland; n = 3712) neighborhoods. Pretax consumption (2014) was compared with a weighted average of 3 years of posttax consumption. Results At baseline, SSBs were consumed 1.25 times per day (95% confidence interval [CI] = 1.00, 1.50) in Berkeley and 1.27 times per day (95% CI = 1.13, 1.42) in comparison city neighborhoods. When we adjusted for covariates, consumption in Berkeley declined by 0.55 times per day (95% CI = −0.75, −0.35) for SSBs and increased by 1.02 times per day (95% CI = 0.54, 1.50) for water. Changes in consumption in Berkeley were significantly different from those in the comparison group, which saw no significant changes. Conclusions Reductions in SSB consumption were sustained in demographically diverse Berkeley neighborhoods over the first 3 years of an SSB tax, relative to comparison cities. These persistent, longer-term reductions in SSB consumption suggest that SSB taxes are an effective policy option for jurisdictions focused on improving public health.
Abnormal expression of estrogen receptor is associated with thin endometrium

Abstract This study was conducted to investigate the association of estrogen receptor (ER) and progesterone receptor (PR) expressions with thin endometrium. Patients with endometrial thickness of less than 7 mm were classified as the study group, while the control group was comprised of patients with endometrial thickness of 7 to 14 mm. The expressions of ER and PR were detected with semi-quantitative immunohistochemical analysis, and the differences were compared between the two groups. The expression of ER was significantly decreased (p < .05) in the stromal cells of thin endometrium during both proliferative and secretory phases as compared to those of normal endometrium. Likewise, ER expression was found to be lower in the glandular cells of thin endometrium than those of normal endometrium during proliferative phase. However, no significant differences were observed for the expression of PR in both glandular and stromal cells between the two groups. Thin endometrium was associated with reduced expression of ER in stromal cells both during proliferative and secretory phase, but in glandular epithelial cells only during proliferative phase.
A Semiconducting Polymer Nano-prodrug for Hypoxia-Activated Photodynamic Cancer Therapy.

Photodynamic therapy (PDT) holds great promise for cancer therapy; however, its efficacy is often compromised by tumor hypoxia. Herein, we report the synthesis of a semiconducting polymer nanoprodrug (SPNpd) that not only efficiently generates singlet oxygen (1 O2 ) under NIR photoirradiation but also specifically activates its chemotherapeutic action in hypoxic tumor microenvironment. SPNpd is self-assembled from a amphiphilic polymer brush, which comprises a light-responsive photodynamic backbone grafted with poly(ethylene glycol) and conjugated with a chemodrug through hypoxia-cleavable linkers. The well-defined and compact nanostructure of SPNpd (30 nm) enables accumulation in the tumor of living mice. Owing to these features, SPNpd exerts synergistic photodynamic and chemo-therapy, and effectively inhibits tumor growth in a xenograft tumor mouse model. This study represents the first hypoxia-activatable phototherapeutic polymeric prodrug system with a high potential for cancer therapy.
Myosin IIA drives membrane bleb retraction

Membrane blebs are specialized cellular protrusions that play diverse roles in processes such as cell division and cell migration. Blebbing can be divided into three distinct phases: bleb nucleation, bleb growth, and bleb retraction. Following nucleation and bleb growth, the actin cortex, comprising actin, cross-linking proteins, and nonmuscle myosin II (MII), begins to reassemble on the membrane. MII then drives the final phase, bleb retraction, which results in reintegration of the bleb into the cellular cortex. There are three MII paralogues with distinct biophysical properties expressed in mammalian cells: MIIA, MIIB, and MIIC. Here we show that MIIA specifically drives bleb retraction during cytokinesis. The motor domain and regulation of the nonhelical tailpiece of MIIA both contribute to its ability to drive bleb retraction. These experiments have also revealed a relationship between faster turnover of MIIA at the cortex and its ability to drive bleb retraction.
Emergency Hospital Admissions for Cardiovascular Diseases and Ambient Levels of Carbon Monoxide: Results for 126 United States Urban Counties, 1999–2005

Background— Evidence on risk of cardiovascular disease (CVD) hospitalization associated with short-term exposure to outdoor carbon monoxide (CO), an air pollutant primarily generated by traffic, is inconsistent across studies. Uncertainties remain on the degree to which associations are attributable to other traffic pollutants and whether effects persist at low levels. Methods and Results— We conducted a multisite time-series study to estimate risk of CVD hospitalization associated with short-term CO exposure in 126 US urban counties during 1999–2005 for >9.3 million Medicare enrollees aged ≥65 years. We considered models with adjustment by other traffic-related pollutants: NO2, fine particulate matter (with aerodynamic diameter ≤2.5 &mgr;m), and elemental carbon. We found a positive and statistically significant association between same-day CO and increased risk of hospitalization for multiple CVD outcomes (ischemic heart disease, heart rhythm disturbances, heart failure, cerebrovascular disease, total CVD). The association remained positive and statistically significant but was attenuated with copollutant adjustment, especially NO2. A 1-ppm increase in same-day daily 1-hour maximum CO was associated with a 0.96% (95% posterior interval, 0.79%, 1.12%) increase in risk of CVD admissions. With same-day NO2 adjustment, this estimate was 0.55% (0.36%, 0.74%). The risk persisted at low CO levels <1 ppm. Conclusions— We found evidence of an association between short-term exposure to ambient CO and risk of CVD hospitalizations, even at levels well below current US health-based regulatory standards. This evidence indicates that exposure to current CO levels may still pose a public health threat, particularly for persons with CVD.
Cost-Effectiveness of Prasugrel Versus Clopidogrel in Patients With Acute Coronary Syndromes and Planned Percutaneous Coronary Intervention: Results From the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction TRI

Background— In patients with acute coronary syndromes and planned percutaneous coronary intervention, the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) demonstrated that treatment with prasugrel versus clopidogrel was associated with reduced rates of cardiovascular death, MI, or stroke and an increased risk of major bleeding. We evaluated the cost-effectiveness of prasugrel versus clopidogrel from the perspective of the US healthcare system by using data from TRITON-TIMI 38. Methods and Results— Detailed resource use data were prospectively collected for all patients recruited from 8 countries (United States, Australia, Canada, Germany, Italy, Spain, United Kingdom, and France; n=3373 prasugrel, n=3332 clopidogrel). Hospitalization costs were estimated on the basis of diagnosis-related group and in-hospital complications. Cardiovascular medication costs were estimated by using net wholesale prices (clopidogrel=$4.62/d; prasugrel=$5.45/d). Life expectancy was estimated from in-trial cardiovascular and bleeding events with the use of statistical models of long-term survival from a similar population from the Saskatchewan Health Database. Over a median follow-up of 14.7 months, average total costs (including study drug) were $221 per patient lower with prasugrel (95% confidence interval, −759 to 299), largely because of a lower rate of rehospitalization involving percutaneous coronary intervention. Prasugrel was associated with life expectancy gains of 0.102 years (95% confidence interval, 0.030 to 0.180), primarily because of the decreased rate of nonfatal MI. Thus, compared with clopidogrel, prasugrel was an economically dominant treatment strategy. If a hypothetical generic cost for clopidogrel of $1/d is used, the incremental net cost with prasugrel was $996 per patient, yielding an incremental cost-effectiveness ratio of $9727 per life-year gained. Conclusion— Among acute coronary syndrome patients with planned percutaneous coronary intervention, treatment with prasugrel versus clopidogrel for up to 15 months is an economically attractive treatment strategy. Clinical Trial Registration— clinicaltrials.gov. Unique identifier: NCT00097591.
Artificial Intelligence and Black-Box Medical Decisions: Accuracy versus Explainability.

Although decision-making algorithms are not new to medicine, the availability of vast stores of medical data, gains in computing power, and breakthroughs in machine learning are accelerating the pace of their development, expanding the range of questions they can address, and increasing their predictive power. In many cases, however, the most powerful machine learning techniques purchase diagnostic or predictive accuracy at the expense of our ability to access "the knowledge within the machine. " Without an explanation in terms of reasons or a rationale for particular decisions in individual cases, some commentators regard ceding medical decision-making to black box systems as contravening the profound moral responsibilities of clinicians. I argue, however, that opaque decisions are more common in medicine than critics realize. Moreover, as Aristotle noted over two millennia ago, when our knowledge of causal systems is incomplete and precarious-as it often is in medicine-the ability to explain how results are produced can be less important than the ability to produce such results and empirically verify their accuracy.
A critical assessment of case reports describing absent uterus in subjects with oestrogen deficiency

The dual diagnosis of hypoplastic uterus in association with ovarian dysgenesis is regularly reported but the pathogenesis of the association is unclear. The uterus, however, may be invisible to all imaging modalities without at least six months of exogenous oestrogen exposure in complete ovarian failure. We assessed all available case reports in this category to estimate whether the apparent association between primary ovarian insufficiency or Turner syndrome and Mullerian agenesis can be largely accounted for by oestrogen deficiency.
The Italian Words and Sentences MB-CDI: normative data and concordance between complete and short forms

Abstract One of the most popular and widely used parent report instruments for assessing early language acquisition is the MacArthur-Bates Communicative Development Inventories (MB-CDI). This study compares normative data of the Italian Words and Sentences complete form (WS-CF) and short form (WS-SF). The samples included 752 children for the WS-CF and 816 children for the WS-SF designed for children aged 18–36 months. The concordance between WS-SF and WS-CF is analyzed in a subgroup of 65 children. The results revealed strong correlations between WS-CF and WS-SF in both lexical and grammar skills as well as strong relationship between lexical and grammar skills. There was a high percentage agreement (97%) between the two forms for scores below the 10th percentile, suggesting that the two forms may be used interchangeably in order to describe vocabulary and grammatical development.
Carbohydrate antigen expression and anti‐pig antibodies in New World capuchin monkeys: Relevance to studies of xenotransplantation

Old World non‐human primates (OWNHPs) are used for preclinical pig‐to‐NHP studies. However, like pigs, OWNHPs express Neu5Gc, and therefore do not develop natural anti‐Neu5Gc antibodies. New World NHPs (NWNHPs) have been reported not to express Neu5Gc. We investigated the potential of NWNHPs in xenotransplantation research.