On July 7, 2023, at 1:21 am, a fire was declared in a retirement home in Milan, Italy. The number of casualties (n = 87) according to the Simple Triage and Rapid Treatment (START) triage system was ...categorized as 65 green, 14 yellow, 2 red, and 6 black; 75% were women, and the mean age was 85.1 years (± 9). Most patients were unable to walk. A total of 30 basic life support (BLS) ambulances, 3 advanced cardiac life support (ACLS) teams on fast cars, 2 buses, and 1 coordination team were deployed. A scoop and run approach was adopted with patients being transported to 15 health care facilities. The event was terminated at 5:43 am. Though the local mass casualty incident (MCI) response plan was correctly applied, the evacuation of the building was difficult due to the age and comorbidities of the patients. START failed to correctly identify patients categorized as minor. Communication problems arose on site that led to the late evacuation of critical patients.
Glass in jewelry is often regarded with both reverence and fear, a delicate material that offers infinite possibilities through the many ways it can be worked to achieve different results. Certain ...processing techniques, especially in relation to the use of glass in combination with metals, reflects both the times and tastes of the present era as well as the language of jewelry at a conceptual and subtle level.
Curcumin, the dietary polyphenol isolated from
(turmeric), is commonly used as an herb and spice worldwide. Because of its bio-pharmacological effects curcumin is also called "spice of life", in fact ...it is recognized that curcumin possesses important proprieties such as anti-oxidant, anti-inflammatory, anti-microbial, antiproliferative, anti-tumoral, and anti-aging. Neurodegenerative diseases such as Alzheimer's Diseases, Parkinson's Diseases, and Multiple Sclerosis are a group of diseases characterized by a progressive loss of brain structure and function due to neuronal death; at present there is no effective treatment to cure these diseases. The protective effect of curcumin against some neurodegenerative diseases has been proven by in vivo and in vitro studies. The current review highlights the latest findings on the neuroprotective effects of curcumin, its bioavailability, its mechanism of action and its possible application for the prevention or treatment of neurodegenerative disorders.
In this paper we study a stochastic gradient algorithm which rules the increase of the mini-batch size in a predefined fashion and automatically adjusts the learning rate by means of a monotone or ...non-monotone line search procedure. The mini-batch size is incremented at a suitable a priori rate throughout the iterative process in order that the variance of the stochastic gradients is progressively reduced. The a priori rate is not subject to restrictive assumptions, allowing for the possibility of a slow increase in the mini-batch size. On the other hand, the learning rate can vary non-monotonically throughout the iterations, as long as it is appropriately bounded. Convergence results for the proposed method are provided for both convex and non-convex objective functions. Moreover it can be proved that the algorithm enjoys a global linear rate of convergence on strongly convex functions. The low per-iteration cost, the limited memory requirements and the robustness against the hyperparameters setting make the suggested approach well-suited for implementation within the deep learning framework, also for GPGPU-equipped architectures. Numerical results on training deep neural networks for multi-class image classification show a promising behaviour of the proposed scheme with respect to similar state of the art competitors.
Abstract
i-Motifs (iMs) are four-stranded DNA structures that form at cytosine (C)-rich sequences in acidic conditions in vitro. Their formation in cells is still under debate. We performed CUT&Tag ...sequencing using the anti-iM antibody iMab and showed that iMs form within the human genome in live cells. We mapped iMs in two human cell lines and recovered C-rich sequences that were confirmed to fold into iMs in vitro. We found that iMs in cells are mainly present at actively transcribing gene promoters, in open chromatin regions, they overlap with R-loops, and their abundance and distribution are specific to each cell type. iMs with both long and short C-tracts were recovered, further extending the relevance of iMs. By simultaneously mapping G-quadruplexes (G4s), which form at guanine-rich regions, and comparing the results with iMs, we proved that the two structures can form in independent regions; however, when both iMs and G4s are present in the same genomic tract, their formation is enhanced. iMs and G4s were mainly found at genes with low and high transcription rates, respectively. Our findings support the in vivo formation of iM structures and provide new insights into their interplay with G4s as new regulatory elements in the human genome.
Lay Summary
Among the secondary structures alternative to the DNA double helix, i-Motifs (iMs) and G-quadruplexes (G4s) are four-stranded non-canonical nucleic acid structures that form in cytosine- and guanine-rich regions, respectively. Because iMs fold in vitro under acidic conditions, they were long thought to form only in vitro. We now show that iMs, like G4s, form in live human cells mainly at gene promoters in open chromatin. iMs that are unstable in vitro still form in cells. iMs and G4s are cell-type specific and associated with increased transcription; however, transcript levels are remarkably different: low for iMs and high for G4s, indicating their distinct activity as regulators of the cell transcriptome. The iM/G4 interplay may represent a novel therapeutic target in disease.
Graphical Abstract
Graphical Abstract
Epidemiology of celiac disease (CD) is increasing. CD mainly presents in early childhood with small intestinal villous atrophy and signs of malabsorption. Compared to healthy individuals, CD patients ...seemed to be characterized by higher numbers of Gram-negative bacteria and lower numbers Gram-positive bacteria.
This study aimed at investigating the microbiota and metabolome of 19 celiac disease children under gluten-free diet (treated celiac disease, T-CD) and 15 non-celiac children (HC). PCR-denaturing gradient gel electrophoresis (DGGE) analyses by universal and group-specific primers were carried out in duodenal biopsies and faecal samples. Based on the number of PCR-DGGE bands, the diversity of Eubacteria was the higher in duodenal biopsies of T-CD than HC children. Bifidobacteria were only found in faecal samples. With a few exceptions, PCR-DGGE profiles of faecal samples for Lactobacillus and Bifidobacteria differed between T-CD and HC. As shown by culture-dependent methods, the levels of Lactobacillus, Enterococcus and Bifidobacteria were confirmed to be significantly higher (P = 0.028; P = 0.019; and P = 0.023, respectively) in fecal samples of HC than in T-CD children. On the contrary, cell counts (CFU/ml) of presumptive Bacteroides, Staphylococcus, Salmonella, Shighella and Klebsiella were significantly higher (P = 0.014) in T-CD compared to HC children. Enterococcus faecium and Lactobacillus plantarum were the species most diffusely identified. This latter species was also found in all duodenal biopsies of T-CD and HC children. Other bacterial species were identified only in T-CD or HC faecal samples. As shown by Randomly Amplified Polymorphic DNA-PCR analysis, the percentage of strains identified as lactobacilli significantly (P = 0.011) differed between T-CD (ca. 26.5%) and HC (ca. 34.6%) groups. The metabolome of T-CD and HC children was studied using faecal and urine samples which were analyzed by gas-chromatography mass spectrometry-solid-phase microextraction and 1H-Nuclear Magnetic Resonance. As shown by Canonical Discriminant Analysis of Principal Coordinates, the levels of volatile organic compounds and free amino acids in faecal and/or urine samples were markedly affected by CD.
As shown by the parallel microbiology and metabolome approach, the gluten-free diet lasting at least two years did not completely restore the microbiota and, consequently, the metabolome of CD children. Some molecules (e.g., ethyl-acetate and octyl-acetate, some short chain fatty acids and free amino acids, and glutamine) seems to be metabolic signatures of CD.
Since the outbreak, in 2019, of COVID-19, the world has experienced marked changes in daily habits, partly reflecting the exceptional social restrictions and health measures adopted to contain the ...disease. All these measures significantly affected not only peoples's daily lives and psychological well-being but also the possibility for the healthcare system to function properly. In this setting, brain tumour patients were at risk due to their higher physical and mental fragility and their need for regular care. The aim of the present study was to assess, using a self-reported online questionnaire, the patients's perceptions regarding their disease experience.
We developed an online anonymous self-report survey to assess patients's disease experience during the pandemic. We investigated the impact of the COVID-19 pandemic on patients's cancer care schedules, their psychological distress and emotions felt during the pandemic, their levels of worry about COVID-19, and their oncological conditions.
107 patients answered our survey, most of them suffering from a glioma. Less than one-third of the sample had their appointments cancelled, delayed or converted into online visits due to the pandemic. Of the patients who answered the survey, 95% declared they were satisfied with their Institute's oncological management. The feelings reported most often were peacefulness or anxiety/worry; the majority of the sample reported high levels of loneliness, which tended to increase with age, whilst the psychological distress was correlated with age and with having a recurrence of the disease. Half of the sample declared severe worry about their oncological condition, in particular subjects with a recurrence or who were receiving adjuvant therapies. Patients with recurrence tended to worry more about the possibility of contracting COVID-19, and its effects.
Our findings illustrate how fragile and in need of care patients with a brain tumour may be, especially those with more severe clinical conditions. These data may help boost healthcare professionals's knowledge about brain tumour patients's needs and fears, so as to be able to offer them a better hospital experience and improve their clinical management, while possibly also reducing the psychological burden on patients and their families.
G-quadruplexes are four-stranded conformations of nucleic acids that act as cellular epigenetic regulators. A dynamic G-quadruplex forming region in the HIV-1 LTR promoter represses HIV-1 ...transcription when in the folded conformation. This activity is enhanced by nucleolin, which induces and stabilizes the HIV-1 LTR G-quadruplexes. In this work by a combined pull-down/mass spectrometry approach, we consistently found hnRNP A2/B1 as an additional LTR-G-quadruplex interacting protein. Surface plasmon resonance confirmed G-quadruplex specificity over linear sequences and fluorescence resonance energy transfer analysis indicated that hnRNP A2/B1 is able to efficiently unfold the LTR G-quadruplexes. Evaluation of the thermal stability of the LTR G-quadruplexes in different-length oligonucleotides showed that the protein is fit to be most active in the LTR full-length environment. When hnRNP A2/B1 was silenced in cells, LTR activity decreased, indicating that the protein acts as a HIV-1 transcription activator. Our data highlight a tightly regulated control of transcription based on G-quadruplex folding/unfolding, which depends on interacting cellular proteins. These findings provide a deeper understanding of the viral transcription mechanism and may pave the way to the development of drugs effective against the integrated HIV-1, present both in actively and latently infected cells.
Many optimization problems arising from machine learning applications can be cast as the minimization of the sum of two functions: the first one typically represents the expected risk, and in ...practice it is replaced by the empirical risk, and the other one imposes a priori information on the solution. Since in general the first term is differentiable and the second one is convex, proximal gradient methods are very well suited to face such optimization problems. However, when dealing with large-scale machine learning issues, the computation of the full gradient of the differentiable term can be prohibitively expensive by making these algorithms unsuitable. For this reason, proximal stochastic gradient methods have been extensively studied in the optimization area in the last decades. In this paper we develop a proximal stochastic gradient algorithm which is based on two main ingredients. We indeed combine a proper technique to dynamically reduce the variance of the stochastic gradients along the iterative process with a descent condition in expectation for the objective function, aimed to fix the value for the steplength parameter at each iteration. For general objective functionals, the a.s. convergence of the limit points of the sequence generated by the proposed scheme to stationary points can be proved. For convex objective functionals, both the a.s. convergence of the whole sequence of the iterates to a minimum point and an
O
(
1
/
k
)
convergence rate for the objective function values have been shown. The practical implementation of the proposed method does not need neither the computation of the exact gradient of the empirical risk during the iterations nor the tuning of an optimal value for the steplength. An extensive numerical experimentation highlights that the proposed approach appears robust with respect to the setting of the hyperparameters and competitive compared to state-of-the-art methods.
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