Miracle-dz/UniFAR-FTUs huggingface dataset:
The Bioidentical Hormone Debate: Are Bioidentical Hormones (Estradiol, Estriol, and Progesterone) Safer or More Efficacious than Commonly Used Synthetic Versions in Hormone Replacement Therapy?

Abstract Background: The use of bioidentical hormones, including progesterone, estradiol, and estriol, in hormone replacement therapy (HRT) has sparked intense debate. Of special concern is their relative safety compared with traditional synthetic and animal-derived versions, such as conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), and other synthetic progestins. Proponents for bioidentical hormones claim that they are safer than comparable synthetic and nonhuman versions of HRT. Yet according to the US Food and Drug Administration and The Endocrine Society, there is little or no evidence to support claims that bioidentical hormones are safer or more effective. Objective: This paper aimed to evaluate the evidence comparing bioidentical hormones, including progesterone, estradiol, and estriol, with the commonly used nonbioidentical versions of HRT for clinical efficacy, physiologic actions on breast tissue, and risks for breast cancer and cardiovascular disease. Methods: Published papers were identified from PubMed/MEDLINE, Google Scholar, and Cochrane databases, which included keywords associated with bioidentical hormones, synthetic hormones, and HRT. Papers that compared the effects of bioidentical and synthetic hormones, including clinical outcomes and in vitro results, were selected. Results: Patients report greater satisfaction with HRTs that contain progesterone compared with those that contain a synthetic progestin. Bioidentical hormones have some distinctly different, potentially opposite, physiological effects compared with their synthetic counterparts, which have different chemical structures. Both physiological and clinical data have indicated that progesterone is associated with a diminished risk for breast cancer, compared with the increased risk associated with synthetic progestins. Estriol has some unique physiological effects, which differentiate it from estradiol, estrone, and CEE. Estriol would be expected to carry less risk for breast cancer, although no randomized controlled trials have been documented. Synthetic progestins have a variety of negative cardiovascular effects, which may be avoided with progesterone. Conclusion: Physiological data and clinical outcomes demonstrate that bioidentical hormones are associated with lower risks, including the risk of breast cancer and cardiovascular disease, and are more efficacious than their synthetic and animal-derived counterparts. Until evidence is found to the contrary, bioidentical hormones remain the preferred method of HRT. Further randomized controlled trials are needed to delineate these differences more clearly.
A Computational Model of Perceived Agency in Video Games

Agency, being one's ability to perform an action and have some influence over the world, is fundamental to interactive entertainment. Although much of the games industry is concerned with providing more agency to its players, what seems to matter more is how much agency each player will actually perceive. In this paper, we present a computational model of this phenomena, based on the notion that the amount of agency that one perceives depends on how much they desire the outcomes that result from their decisions. Using a structure for high-agency stories that we designed specifically for this intent, we present the results of a 141-participant user study that tests our model's ability to select subsequent events in an original interactive story. Using a newly validated survey instrument for measuring both agency and fun, we found with a high degree of confidence that event sequences selected by our model result in players perceiving more agency than players who experience event sequences that our model does not recommend.
The effect of pyridostigmine on bispectral index during recovery from sevoflurane anesthesia

Background There have been some conflicting reports showing that muscle relaxants and anticholinesterases affect the level of the bispectral index (BIS). The purpose of this study was to investigate whether pyridostigmine affects the level of the BIS during recovery from sevoflurane anesthesia. Methods Fifty-two adult patients scheduled for laparoscopic cholecystectomy and laparoscopic appendectomy. Anesthesia was induced with thiopental 4 mg/kg and rocuronium 0.6 mg/kg. The lung was mechanically ventilated with 1-3 vol% sevoflurane, 50% oxygen and 50% nitrous oxide. After a specimen was removed, the sevoflurane concentration was maintained at 1.5 vol%. When skin closure began, sevoflurane was stopped; however, 50% oxygen and 50% nitrous oxide were maintained. The patients then received either (1) a group that received an injection of glycopyrrolate 0.04 mg/kg and pyridostigmine 0.2 mg/kg (reverse (R) group, n = 26) or (2) a group that received normal saline (control (C) group, n = 26). Group assignment was random. Pyridostigmine, a reversible cholinesterase inhibitor, is a parasympathomimetic. End-tidal sevoflurane concentration, train of four (TOF) ratio, bispectral index (BIS), blood pressure and heart rate were measured from the end of the operation to 15 min after inject of pyridostigmine or placebo. Results There were no significant between group differences in the time dependent decrease in end-tidal sevoflurane concentration (P = 0.0642). There were significant differences between the two groups for the time course for increases in the TOF value (P < 0.0001). There were significant differences between the two groups for the time course for increases in the BIS value (P = 0.0107). There were no significant differences in the mean BIS value up to 10 minutes after administering drug, but 15 minutes after administrating the reverse drug or the control drug, the BIS value showed significantly different BIS values: 68.2 ± 6.2 (Group R) and 63.2 ± 6.2 (Group C) (P = 0.0058). Conclusions The finding that pyridostigmine increases TOF and BIS suggests that pyridostigmine may enhance recovery during recovery from sevoflurane anesthesia.
Antibiotics induce redox-related physiological alterations as part of their lethality

Significance Substantial knowledge exists about how antibiotics interfere with core bacterial processes by binding to specific targets. Recently it has become appreciated that blocking these functions alters cellular redox state, and these perturbations may contribute to the lethality of antibiotics. In this work we explore whether antibiotic treatment of bacteria affects cellular oxidative stress and the role of such stress in antibiotic-mediated killing. We find that antibiotics dynamically alter cellular respiration and induce lethal levels of intracellular hydrogen peroxide. Antioxidants, including oxidative stress defense proteins, significantly reduce the killing by antibiotics, which is highly sensitive to the presence of molecular oxygen. These findings underscore the complex nature of antibiotic action and suggest practical approaches to enhancing our current antibiotic arsenal. Deeper understanding of antibiotic-induced physiological responses is critical to identifying means for enhancing our current antibiotic arsenal. Bactericidal antibiotics with diverse targets have been hypothesized to kill bacteria, in part by inducing production of damaging reactive species. This notion has been supported by many groups but has been challenged recently. Here we robustly test the hypothesis using biochemical, enzymatic, and biophysical assays along with genetic and phenotypic experiments. We first used a novel intracellular H2O2 sensor, together with a chemically diverse panel of fluorescent dyes sensitive to an array of reactive species to demonstrate that antibiotics broadly induce redox stress. Subsequent gene-expression analyses reveal that complex antibiotic-induced oxidative stress responses are distinct from canonical responses generated by supraphysiological levels of H2O2. We next developed a method to quantify cellular respiration dynamically and found that bactericidal antibiotics elevate oxygen consumption, indicating significant alterations to bacterial redox physiology. We further show that overexpression of catalase or DNA mismatch repair enzyme, MutS, and antioxidant pretreatment limit antibiotic lethality, indicating that reactive oxygen species causatively contribute to antibiotic killing. Critically, the killing efficacy of antibiotics was diminished under strict anaerobic conditions but could be enhanced by exposure to molecular oxygen or by the addition of alternative electron acceptors, indicating that environmental factors play a role in killing cells physiologically primed for death. This work provides direct evidence that, downstream of their target-specific interactions, bactericidal antibiotics induce complex redox alterations that contribute to cellular damage and death, thus supporting an evolving, expanded model of antibiotic lethality.
Multimode fiber optical imaging using wavefront control

Optical microscopy enables us to observe at high resolution and with a large field of view objects otherwise invisible for the naked eye. This is why it is becoming a fundamental tool in biology and in diagnostics, where observation at cellular level can tell about the health status of a tissue. At visible wavelengths, light undergoes scattering when propagating through tissues, limiting the imaging depth to the first cellular layers of a biological sample. Endoscopic approaches allow the bypass of the scattering layers and move the accessible volume centimeters inside tissues, ideally keeping large field of view and high-resolution capabilities. In this thesis we explore the combination of wavefront control and ultrathin multimode optical fibers to develop a new family of endoscopes able to generate images with micrometric resolution being, at the same time, minimally invasive. We demonstrate that a variety of imaging techniques can be implemented in optical fiber-based endoscopy, maximizing the amount of information that can be collected through a few hundreds of micrometers-thick probe. Firstly, we describe digital phase conjugation (DPC), which is the utilized wavefront shaping technique to convert a multimode optical fiber in an ultrathin endoscope. The use of DPC in synergy with multimode optical fibers resulted in ultrathin probes able to perform fluorescence imaging, photoacoustic imaging, and multiphoton imaging. Moreover, we show that using saturation excitation of fluorescent samples we can beat the resolution limit imposed by the numerical aperture of the optical fiber and obtain optical sectioning. In the first part of the thesis we describe which steps have been performed towards the implementation of these techniques. In the second part, we exploit coherent fiber bundles as imaging probes. This kind of fiber is typically utilized in endoscopy, but their resolution is limited by the distance between the fiberâs cores. Here we show two techniques - one based on DPC and a second based on statistical properties of speckle patterns - to obtain images with a better resolution than the one imposed by the core-to-core spacing, both relying on a unique property of multicore fibers: the memory effect. We also accomplished complex pattern transmission through multicore fibers with high resolution. Overall, the presented work provides new insights in imaging through optical fibers based on wavefront shaping techniques, opening up pathways for addressing current issues in this research field.
Synthesis of Chiral 1,4-Disubstituted-1,2,3-Triazole Derivatives from Amino Acids

A versatile method for the synthesis of chiral 1,4-disubstituted-1,2,3-triazole derivatives starting from easily accessible naturally occurring D-or L-amino acids as chiral synthons is described. The amino acids were converted into azido alcohols, followed by copper catalyzed [3+2] cycloaddition reactions between the azido alcohols and methyl propiolate and subsequent ester aminolysis with primary and secondary amines furnished the target compounds, which were obtained in excellent yields with no racemization. Docking of selected target compounds shows that the chiral 1,4-disubstituted-1,2,3-triazoles derivatives has the potential of mimicking the binding mode of known purine analogues.
Atmospheric Chemistry and Physics Aerosol Hygroscopicity in the Marine Atmosphere: a Closure Study Using High-time-resolution, Multiple-rh Dash-sp and Size-resolved C-tof-ams Data

We have conducted the first airborne hygro-scopic growth closure study to utilize data from an Aero-dyne compact Time-of-Flight Aerosol Mass Spectrometer (C-ToF-AMS) coupled with size-resolved, multiple-RH, high-time-resolution hygroscopic growth factor (GF) measurements from the differential aerosol sizing and hygro-scopicity spectrometer probe (DASH-SP). These data were collected off the coast of Central California during seven of the 16 flights carried out during the MASE-II field campaign in July 2007. Two of the seven flights were conducted in airmasses characterized by continental origin. These flights exhibited elevated organic volume fractions (VF organic =0.56±0.19, as opposed to 0.39±0.20 for all other flights), corresponding to significantly suppressed GFs at high RH (1.61±0.14 at 92% RH, as compared with 1.91±0.07 for all other flights), more moderate GF suppression at intermediate RH (1.53±0.10 at 85%, compared with 1.58±0.08 for all other flights), and no measurable GF suppression at low RH (1.31±0.06 at 74%, compared with 1.31±0.07 for all other flights). Organic loadings were slightly elevated in above-cloud aerosols, as compared with below-cloud aerosols, and corresponded to a similar trend of significantly suppressed GF at high RH, but more moderate impacts at lower values of RH. A hygroscopic closure based on a volume-weighted mixing rule provided good agreement with DASH-SP measurements (R 2 =0.78). Minimization of root mean square error between observations and predictions indicated mission-averaged organic GFs of 1.22, 1.45, and 1.48 at 74, 85, and 92% RH, respectively. These values agree with previously reported values for water-soluble or-ganics such as dicarboxylic and multifunctional acids, and correspond to a highly oxidized, presumably water-soluble, organic fraction (mission-averaged O:C=0.92±0.33). Finally , a backward stepwise linear regression revealed that, other than RH, the most important predictor for GF is VF organic , indicating that a simple emperical model relating GF, RH, and the relative abundance of organic material can provide accurate predictions (R 2 =0.77) of hygroscopic growth for the California coast.
Nanocrystalline SiC metal-semiconductor-metal photodetector with ZnO nanorod arrays for high-temperature applications

This work demonstrates a method to develop high temperature metal-semiconductor-metal photodetectors using low-temperature, ion beam assisted deposition of nanocrystalline silicon carbide (SiC) and hydrothermal synthesis of zinc oxide (ZnO) nanorod arrays. Due to incorporation of ZnO nanorod arrays, the photo-to-dark current ratio of Au/nanocrystalline SiC is increased from 4.9 to 13.3 at 25°C and from 4.85 to 7.57 at 200°C. The results, suggest that the ZnO nanorod arrays could serve as an antireflection layers to guide more light into the SiC photodetectors. These preliminary results support the integration of nanocrystalline SiC and ZnO nanorod arrays for use in high temperature photo-detection applications.
Ghrelin in Central Neurons

Ghrelin, an orexigenic peptide synthesized by endocrine cells of the gastric mucosa, is released in the bloodstream in response to a negative energetic status. Since discovery, the hypothalamus was identified as the main source of ghrelin in the CNS, and effects of the peptide have been mainly observed in this area of the brain. In recent years, an increasing number of studies have reported ghrelin synthesis and effects in specific populations of neurons also outside the hypothalamus. Thus, ghrelin activity has been described in midbrain, hindbrain, hippocampus, and spinal cord. The spectrum of functions and biological effects produced by the peptide on central neurons is remarkably wide and complex. It ranges from modulation of membrane excitability, to control of neurotransmitter release, neuronal gene expression, and neuronal survival and proliferation. There is not at present a general consensus concerning the source of ghrelin acting on central neurons. Whereas it is widely accepted that the hypothalamus represents the most important endogenous source of the hormone in CNS, the existence of extra-hypothalamic ghrelin-synthesizing neurons is still controversial. In addition, circulating ghrelin can theoretically be another natural ligand for central ghrelin receptors. This paper gives an overview on the distribution of ghrelin and its receptor across the CNS and critically analyses the data available so far as regarding the effects of ghrelin on central neurotransmission.
Role of microRNAs in cardiac development and disease

Heart disease-related deaths are the highest in most societies and congenital heart diseases account for approximately 40% of prenatal deaths and over 20% of mortality in the first few months after birth. Congenital heart disease affects approximately 1% of all newborns and is the causative factor for more deaths within the first year of life as compared to all other genetic defects. Advances in treatment approaches increased life expectancy and led to an expansion of adult population with clinical manifestation of congenital heart defects in up to 90% of the children born with congenital heart diseases. Regulation of cardiac gene expression involves multiple independent enhancers that play a critical role in maintaining a restricted and specific pattern of gene expression in the heart. Cardiac transcriptional pathways are intimately regulated by microRNAs (miRNAs), which are small, regulatory RNAs, approximately 22 nucleotides in length, also coded by specific genes. These miRNAs act as suppressors of gene expression by inhibiting translation and/or promoting degradation of target protein-coding mRNAs. There are several miRNAs involved in the development of heart and dysregulation of specific miRNAs is associated with congenital and other cardiac defects. Stress responsive cardiac hypertrophy is orchestrated among other factors, by specific miRNAs. miRNAs such as miR-499 are considered useful as biomarkers of a given heart disease. Therapeutic application of miRNAs is also envisaged considering the small size and specific effects of these molecules. In this review, we addressed different roles of miRNAs in the development and diseases of the heart.
Phosphorylation of p27Kip1 Regulates Assembly and Activation of Cyclin D1-Cdk4

ABSTRACT p27 mediates Cdk2 inhibition and is also found in cyclin D1-Cdk4 complexes. The present data support a role for p27 in the assembly of D-type cyclin-Cdk complexes and indicate that both cyclin D1-Cdk4-p27 assembly and kinase activation are regulated by p27 phosphorylation. Prior work showed that p27 can be phosphorylated by protein kinase B/Akt (PKB/Akt) at T157 and T198. Here we show that PKB activation and the appearance of p27pT157 and p27pT198 precede p27-cyclin D1-Cdk4 assembly in early G1. PI3K/PKB inhibition rapidly reduced p27pT157 and p27pT198 and dissociated cellular p27-cyclin D1-Cdk4. Mutant p27 allele products lacking phosphorylation at T157 and T198 bound poorly to cellular cyclin D1 and Cdk4. Cellular p27pT157 and p27pT198 coprecipitated with Cdk4 but were not detected in Cdk2 complexes. The addition of p27 to recombinant cyclin D1 and Cdk4 led to cyclin D1-Cdk4-p27 complex formation in vitro. p27 phosphorylation by PKB increased p27-cyclin D1-Cdk4 assembly in vitro but yielded inactive Cdk4. In contrast, Src pretreatment of p27 did not affect p27-cyclin D1-Cdk4 complex formation. However, Src treatment led to tyrosine phosphorylation of p27 and catalytic activation of assembled cyclin D1-Cdk4-p27 complexes. Thus, while PKB-dependent p27 phosphorylation appears to increase cyclin D1-Cdk4-p27 assembly or stabilize these complexes in vitro, cyclin D1-Cdk4-p27 activation requires the tyrosine phosphorylation of p27. Constitutive activation of PKB and Abl or Src family kinases in cancers would drive p27 phosphorylation, increase cyclin D1-Cdk4 assembly and activation, and reduce the cyclin E-Cdk2 inhibitory function of p27. Combined therapy with both Src and PI3K/PKB inhibitors may reverse this process.
Connecting Genes with Diseases

This paper presents a visual data mining approach using the combination of clinical data, pathways and gene-expression data. The visual exploration of medical data using pathways to navigate and filter the data allows a more systematic and efficient investigation of problems in modern life science. A multiplicity of hypothesis can be evaluated in the same period of time, enabling a much better exploitation of the data. We present a system for data preprocessing and automatic classification, a set of visualization views and finally the integration in the Caleydo visualization framework, which enables the “coupling” of genetic and a broad spectrum of clinical data. With the help of the Caleydo framework the medical expert can identify connections between genetic parameters, patient subgroups, and drug responses.
Development and Study of Organic Polymer Resistive Memories For Crossbar Architectures

Over the past decade, non-volatile Flash storage technologies have played a major role in the development of mobile electronics and multimedia (MP3, Smartphone, USB, ultraportable computers .). To further enhance performances, increase the capacity and reduce manufacturing costs, new technological solutions are now studied to provide complementary solutions or replace Flash technology. Cited by ITRS, the polymer resistive memories present very promising characteristics: low cost processing and ability for integration at high densities above CMOS interconnections or on flexible substrate. This PhD specifically focused on the development and study of composite material made of Poly-Methyl-Methacrylate (PMMA) polymer resist doped with C60 fullerene molecules. Studies were carried out on three different axes in parallel: Composite materials development & characterization, integration of the organic material in specific test structure and advanced devices and finally detailed electrical characterization of memory cells and performances analysis.