Miracle-dz/UniFAR-FTUs huggingface dataset:
Machine Learning Approach for Determining the Formation of β-Lactam Antibiotic Complexes with Cyclodextrins Using Multispectral Analysis

The problem of determining the formation of complexes of β-lactam antibiotics with cyclodextrins (CDs) and the interactions involved in this process were addressed by machine learning on multispectral images. Complexes of β-lactam antibiotics, including cefuroxime axetil, cefetamet pivoxil, and pivampicillin, as well as CDs, including αCD, βCD, γCD, hydroxypropyl-αCD, methyl-βCD, hydroxypropyl-βCD, and hydroxypropyl-γCD, were prepared in all combinations. Thermograms confirming the formation of cyclodextrin complexes were obtained using differential scanning calorimetry. Transmission Fourier-transform infrared (tFTIR) and complementary attenuated total reflectance FTIR (ATR) coupled with machine learning were techniques chosen as a nondestructive alternative. The machine learning algorithm was used to determine the formation of complexes in samples using solely their tFTIR and ATR spectra at the prediction stage. Parameterized method 7 (PM7) was used to support the analysis by molecular modeling of the complexes. The model developed through machine learning properly distinguished samples with formed complexes form noncomplexed samples with a cross-validation accuracy of 90.4%. Analysis of the contribution of spectral bands to the model indicated interactions of ester groups of β-lactam antibiotics with CDs, as well as some interactions of cephem ring in cefetamet pivoxil and penam moiety in pivampicillin. Molecular modeling with PM7 helped to explain experimental results and allowed to propose possible binding modes.
Chelation Therapy: A New Look at an Old Treatment for Heart Disease, Particularly in Diabetics

Don’t cringe when you hear the term chelation (key-LAY-shun) therapy. If you have heard about it at all, you may have heard that it is alternative medicine, quackery, expensive, and even dangerous. New research funded by the National Institutes of Health is suggesting that this old treatment has some real life in it and that it may particularly benefit patients with diabetes mellitus and prior heart attacks. Chelation therapy was first used in the early 20th century to treat metal poisoning. The treatment involves administering a drug called a chelator, which has a magnetically charged pocket that can “grab” a metal and hang onto it, kind of like a baseball mitt with a magnet in its pocket, allowing the metal to be excreted in the urine. One chelator, calcium ethylenediaminetetraacetic acid (EDTA), is approved by the US Food and Drug Administration to treat lead poisoning. Alternative medicine practitioners have been using a similar chelator, disodium EDTA, to treat heart disease, claiming to see benefits, since the 1950s. Disodium EDTA chelation therapy is usually administered intravenously each week for 20 to 40 sessions. Each intravenous infusion may last …
Association between Lifestyle Factors and CpG Island Methylation in a Cancer-Free Population

Background: Many risk factors have been associated with cancer, such as age, family history, race, smoking, high-fat diet, and poor nutrition. It is important to reveal the molecular changes related to risk factors that could facilitate early detection, prevention, and overall control of cancer. Methods: We selected six cancer-specific methylated genes that have previously been reported in primary tumors and have also been detected in different bodily fluids of cancer patients. Here, we used quantitative fluorogenic real-time methylation-specific PCR in plasma DNA samples for the detection of methylation changes from an asymptomatic population who do not have any known cancer. Results: The promoter methylation frequencies of the studied genes were as follows: APC (7%), CCND2 (22%), GSTP1 (2%), MGMT (9%), RARβ2 (29%), and P16 (3%). Promoter methylation of at least one of the genes analyzed was observed in ∼46% (72 of 157) of the samples by binary dichotomization. Promoter hypermethylation of at least two genes was detected in 17% (26 of 157) of the samples. RARβ2 methylation was observed in 45% of subjects who had a high-fat diet in contrast with those who had a low-fat diet (23%; P = 0.007). Discussion: Our findings may help to elucidate early methylation changes that may lead to cancer development. These methylation changes could be due to exposure to risk factors and may be useful for cancer prevention measures such as changes in lifestyle. Longitudinal follow-up of a high-risk population is needed to understand the association of methylation of candidate genes in cancer development. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2984–91)
Peroxiredoxins and Beyond; Redox Systems Regulating Lung Physiology and Disease.

SIGNIFICANCE The lung is a unique organ, as it is constantly exposed to air, and thus it requires a robust antioxidant defense system to prevent the potential damage from exposure to an array of environmental insults, including oxidants. The peroxiredoxin (PRDX) family plays an important role in scavenging peroxides and is critical to the cellular antioxidant defense system. Recent Advances: Exciting discoveries have been made to highlight the key features of PRDXs that regulate the redox tone. PRDXs do not act in isolation as they require the thioredoxin/thioredoxin reductase/NADPH, sulfiredoxin (SRXN1) redox system, and in some cases glutaredoxin/glutathione, for their reduction. Furthermore, the chaperone function of PRDXs, controlled by the oxidation state, demonstrates the versatility in redox regulation and control of cellular biology exerted by this class of proteins. CRITICAL ISSUES Despite the long-known observations that redox perturbations accompany a number of pulmonary diseases, surprisingly little is known about the role of PRDXs in the etiology of these diseases. In this perspective, we review the studies that have been conducted thus far to address the roles of PRDXs in lung disease, or experimental models used to study these diseases. Intriguing findings, such as the secretion of PRDXs and the formation of autoantibodies, raise a number of questions about the pathways that regulate secretion, redox status, and immune response to PRDXs. FUTURE DIRECTIONS Further understanding of the mechanisms by which individual PRDXs control lung inflammation, injury, repair, chronic remodeling, and cancer, and the importance of PRDX oxidation state, configuration, and client proteins that govern these processes is needed. Antioxid. Redox Signal. 00, 000-000.
Leukocytes from obese individuals exhibit an impaired SPM signature

Specialized proresolving mediators (SPMs) biosynthesized from docosahexaenoic acids (DHAs) including resolvins (Rvs), protectins, and maresins are potent endogenous autacoids that actively resolve inflammation, protect organs, and stimulate tissue regeneration. Our hypothesis was that failure of resolution programs may lead to unremitting inflammation in obesity, contributing to the development of metabolic comorbidities in this condition. Obese individuals with persistent low‐grade systemic inflammation showed reduced leukocyte production of the DHA‐derived monohydroxy fatty acid 17—hydroxy‐DHA (HDHA) and unbalanced formation of SPMs (in particular d‐series Rvs) accompanied by enhanced production of proinflammatory lipid mediators such as leukotriene B4. Mechanistic studies attributed this impairment to reduced 15‐lipoxygenase (LOX) activity rather than altered DHA cellular uptake. Moreover, leukocytes from obese individuals exhibited decreased 5‐LOX levels and reduced 5‐LOX Ser271 phosphorylation and distinct intracellular 5‐LOX redistribution. However, 15‐LOX appears to be the most critical factor for the deficient production of SPMs by obese leukocytes because the formation of d‐series Rvs was completely rescued by incubation with the intermediate precursor 17‐HDHA. These data provide proof of concept that administration of intermediate precursors of SPM biosynthesis (e.g., 17‐HDHA) could be more efficient in overriding impaired formation of these proresolving lipid mediators in conditions characterized by dysfunctional LOX activity, such as obesity. —López‐Vicario, C, Titos, E. , Walker, M. E. , Alcaraz‐Quiles, J., Casulleras, M. , Durán‐Güell, M. , Flores‐Costa, R. , Pérez‐Romero, N. , Forné, M. , Dalli, J., Clària, J. Leukocytes from obese individuals exhibit an impaired SPM signature. FASEB J. 33, 7072–7083 (2019). www.fasebj. org
Identifying the risk factors for catheter-associated urinary tract infections: a large cross-sectional study of six hospitals

Motivation Catheter-associated urinary tract infections (CAUTI) are a common and serious healthcare-associated infection. Despite many efforts to reduce the occurrence of CAUTI, there remains a gap in the literature about CAUTI risk factors, especially pertaining to the effect of catheter dwell-time on CAUTI development and patient comorbidities. Objective To examine how the risk for CAUTI changes over time. Additionally, to assess whether time from catheter insertion to CAUTI event varied according to risk factors such as age, sex, patient type (surgical vs medical) and comorbidities. Design Retrospective cohort study of all patients who were catheterised from 2012 to 2016, including those who did and did not develop CAUTIs. Both paediatric and adult patients were included. Indwelling urinary catheterisation is the exposure variable. The variable is interval, as all participants were exposed but for different lengths of time. Setting Urban academic health system of over 2500 beds. The system encompasses two large academic medical centres, two community hospitals and a paediatric hospital. Results The study population was 47 926 patients who had 61 047 catheterisations, of which 861 (1.41%) resulted in a CAUTI. CAUTI rates were found to increase non-linearly for each additional day of catheterisation; CAUTI-free survival was 97.3% (CI: 97.1 to 97.6) at 10 days, 88.2% (CI: 86.9 to 89.5) at 30 days and 71.8% (CI: 66.3 to 77.8) at 60 days. This translated to an instantaneous HR of. 49%–1.65% in the 10–60 day time range. Paraplegia, cerebrovascular disease and female sex were found to statistically increase the chances of a CAUTI. Conclusions Using a very large data set, we demonstrated the incremental risk of CAUTI associated with each additional day of catheterisation, as well as the risk factors that increase the hazard for CAUTI. Special attention should be given to patients carrying these risk factors, for example, females or those with mobility issues.
Apoptosis-Related Gene Transcription in Human A549 Lung Cancer Cells via A3 Adenosine Receptor

Background/Aims: Extracellular adenosine induces apoptosis in a variety of cancer cells via diverse signaling pathways. The present study investigated the mechanism underlying adenosine-induced apoptosis in A549 human lung cancer cells. Methods: MTT assay, TUNEL staining, flow cytometry using propidium iodide and annexin V-FITC, real-time RTPCR, Western blotting, monitoring of mitochondrial membrane potentials, and assay of caspase-3, -8, and -9 activities were carried out in A549 cells, and the siRNA to silence the A3 adenosine receptortargeted gene was constructed. Results: Extracellular adenosine induces A549 cell apoptosis in a concentration (0.01-10 mM)-dependent manner, and the effect was inhibited by the A3 adenosine receptor inhibitor MRS1191 or knocking-down A3 adenosine receptor. Like adenosine, the A3 adenosine receptor agonist 2-Cl-IB-MECA also induced A549 cell apoptosis. Adenosine increased expression of mRNAs for Puma, Bax, and Bad, disrupted mitochondrial membrane potentials, and activated caspase-3 and -9 in A549 cells, and those adenosine effects were also suppressed by knocking-down A3 adenosine receptor. Conclusion: Adenosine induces A549 cell apoptosis by upregulating expression of Bax, Bad, and Puma, to disrupt mitochondrial membrane potentials and to activate caspase-9 followed by the effector caspase-3, via A3 adenosine receptor.
A Systematic Review of the Short-Term Health Effects of Air Pollution in Persons Living with Coronary Heart Disease

Persons living with chronic medical conditions (such as coronary artery disease (CAD)) are thought to be at increased risk when exposed to air pollution. This systematic review critically evaluated the short-term health effects of air pollution in persons living with CAD. Original research articles were retrieved systematically through searching electronic databases (e.g., Medical Literature Analysis and Retrieval System Online (MEDLINE)), cross-referencing, and the authors’ knowledge. From 2884 individual citations, 26 eligible articles were identified. The majority of the investigations (18 of 22 (82%)) revealed a negative relationship between air pollutants and cardiac function or overall health. Heart rate variability (HRV) was the primary cardiovascular outcome measure, with 10 out of 13 studies reporting at least one index of HRV being significantly affected by air pollutants. However, there was some inconsistency in the relationship between HRV and air pollutants, mediated (at least in part) by the confounding effects of beta-blocker medications. In conclusion, there is strong evidence that air pollution can have adverse effects on cardiovascular function in persons living with CAD. All persons living with CAD should be educated on how to monitor air quality, should recognize the potential risks of excessive exposure to air pollution, and be aware of strategies to mitigate these risks. Persons living with CAD should minimize their exposure to air pollution by limiting outdoor physical activity participation when the forecast air quality health index indicates increased air pollution (i.e., an increased risk).
Analysis of the burden and variability in the management of NAFLD patients in the clinical practice: unifying the required criteria.

AIM to assess the prevalence of non-alcoholic fatty liver disease (NAFLD) in the gastroenterology outpatient clinic and describe the use of the resources accordingly. METHODS a prospective and observational study of 403 patients seen in the gastroenterology outpatient clinic to rule out liver disease during three randomized months in 2016. The overall prevalence of NAFLD, disease severity, heterogeneity of the final diagnosis, the use of medical resources and their respective cost were analyzed. RESULTS the main reason for consultation was hypertransaminasemia (42.9%, 173/403), followed by hepatitis C virus (HCV) (28.5%, 115/403). NAFLD was identified as the definitive diagnosis in 29.8% (120/403) of the cohort, 69.2% (83/120) derived by hypertransaminasemia and 24.2% (29/120) by steatosis. Laboratory tests were performed in 96.7% (116/120), abdominal ultrasound in 88.3% (106/120), viral serology in 79.2% (95/120) and autoimmunity in 70% (84/120) of patients with NAFLD. Liver fibrosis was not assessed in 87.5% of cases. In a post-hoc analysis, 12.1% (17/120) had advanced fibrosis by FIB-4. On ultrasound, 65% (73/106) had hepatic steatosis and 15% (17/106) chronic liver disease (significant fibrosis). The mean time for diagnosis was 2.23 ± 0.8 visits. The terminology used to define the clinical diagnosis was heterogeneous as follows: a) 48.3% (58/120) hepatic steatosis; b) 15% (18/120) non-alcoholic steatohepatitis; c) 15.8% (19/120) fatty liver; d) 13.3% (16/120) metabolic syndrome; and e) 7.5% (9/120) dual liver disease (fatty liver and alcohol). A pharmacological intervention was performed in six patients, a liver biopsy in two patients and another six were referred to another specialist. The average cost per patient until diagnosis was €570.78, which included analytical, autoantibodies, viral serology and abdominal ultrasound, with a mean of 2.5 consultations. Thus, the total expense in patients with NAFLD was €68,493.6. CONCLUSION NAFLD is a frequent cause of hypertransaminasemia. However, the heterogeneity in the management and terminology of the disease makes it necessary to initiate medical training actions in order to unify the criteria for disease control.
The IBM ASIC/SoC methodology - A recipe for first-time success

This paper describes the methodology employed by the IBM Microelectronics Division for the design of its Blue LogicÂ® application-specific integrated circuits (ASICs) and system-on-a-chip (SoC) designs. This methodology is used by both IBM ASIC and SoC designers, as well as OEM customers. A key focus of the IBM ASIC/SoC methodology, outlined in the first section of this paper, is the first-time-right methods of design and verification that maximize correct operation of the chip upon product integration. The second section of this paper describes advances in methodology that deal with the physical effects of shrinking device geometries and enable design using the performance and density capabilities available in the new technologies, and methodology advances that have improved design turnaround time (TAT) for large, complex designs. Upcoming nanometer-level technologies present new opportunities to integrate systems on a single chip, including functional components of mixed libraries and mixed analog and digital design. The final section of this paper outlines strategies that are enabling SoC design at these levels.
Evaluation of the Efficacy of Sildenafil Citrate Following Severe Head Trauma in an Experimental Rat Model.

AIM This study aims to investigate the acute effects of sildenafil citrate in severe head trauma, a leading cause of death, and to compare it with the efficacy of mannitol, which is an osmotically active agent frequently used in clinically treating head trauma. MATERIAL AND METHODS Twenty-eight Wistar-derived albino strain female rats were randomized into four groups comprising seven rats each. These groups were designated as follows: Group I: sham; Group II: traumatic brain injury (TBI); Group III: TBI + mannitol (20% 1 gr/kg, intraperitoneal); and Group IV: TBI + sildenafil citrate (10 mg/kg, intraperitoneal). Sections prepared following the tissue processing of samples obtained from the right prefrontal cortex and right hippocampal regions of the brains of sacrificed rats were histopathologically evaluated. Fractionator method via the StereoInvestigator software program (MicroBrightField) was used to count the neurons. Pyknotic neuron count and pyknotic/ total neuron count were compared between the groups. RESULTS In the comparison of Group II and IV, pyknotic neuron count (prefrontal; group II: 116.00±30.50, group IV: 80.00±19.47) and pyknotic/ total neuron count (prefrontal; group II: 0,30±0.08, group IV: 0.21±0.02) were significantly lower in Group IV in both regions (p 0.05). Similarly, in the comparison of Group II and III, the values in Group III were lower in both regions (p 0.05). CONCLUSION Sildenafil citrate decreases neuronal death in the acute phase and produces similar results with mannitol. Therefore, we believe that sildenafil citrate can be a useful alternative for clinically treating acute TBI.
Risk Factors of γ-Hydroxybutyrate Overdosing

The aim of this study was to identify in recreational drug users the factors which increase the risk of overdosing (OD) with γ-hydroxybutyrate (GHB). A purposive sample of 45 experienced GHB users was interviewed, equally divided into three groups (never OD, occasional OD, and repeat OD). The repeat OD group scored highest on many risk factors regarding GHB use, the occasional OD group scored intermediate, and the never OD group scored lowest. Participants, whether or not they had overdosed on GHB, most often perceived GHB use (e.g. using more GHB than usual, using GHB doses too closely together) as the main reason for GHB OD, and many participants who had overdosed on GHB reported that they had taken more GHB than usual at their most recent occasion of GHB OD. No significant differences in co-use of GHB with other substances were found between the three groups. Our findings indicate that using GHB in the company of groups of friends probably reduces, but does not eliminate, the risk of OD.
Driven spheres, ellipsoids and rods in explicitly modeled polymer solutions

Understanding the transport of driven nano- and micro-particles in complex fluids is of relevance for many biological and technological applications. Here we perform hydrodynamic multiparticle collision dynamics simulations of spherical and elongated particles driven through polymeric fluids containing different concentrations of polymers. We determine the mean particle velocities which are larger than expected from Stokes law for all particle shapes and polymer densities. Furthermore we measure the fluid flow fields and local polymer density and polymer conformation around the particles. We find that polymer-depleted regions close to the particles are responsible for an apparent tangential slip velocity which accounts for the measured flow fields and transport velocities. A simple two-layer fluid model gives a good match to the simulation results.
Unexpected drug emerges for stroke recovery.

In the hours after a stroke, the clot-busting treatment tissue plasminogen activator can limit damage to the brain. But once that damage is done, no drugs are known to promote recovery. New research suggests such a therapy could come from an unlikely target: a cellular protein called CCR5 that allows HIV to infect cells. Scientists found that in mice, disabling CCR5 helps surviving neurons make new connections, and that people who carry a CCR5 mutation may recover better from a stroke. They hope to launch a clinical trial this year that gives stroke patients an HIV drug that blocks CCR5.
The Interlinked Rising Epidemic of Insufficient Sleep and Diabetes Mellitus

For healthy existence, humans need to spend one-third of their time sleeping. Any qualitative or quantitative disturbances in sleep would result in an increased prevalence of obesity, metabolic disorders, diabetes, cardiovascular diseases, and hypertension. The paper aims to highlight the growing global problem of insufficient sleep and its significant impact on the rising incidence of diabetes mellitus. An extensive literature search was done in all major databases for “insufficient sleep” and “Diabetes Mellitus” for this review. Shorter (<6 h) and longer (>9 h) durations of sleep have been adversely related to insulin resistance. Though the relation between insufficient sleep and diabetes mellitus is more or less understood, little is known about how oversleeping or hypersomnia (10–12 h) increases the risk of diabetes. The relationship between sleep disturbances and diabetes is dual-sided, as chronic sleep disturbances would elevate the risk of developing insulin resistance, while diabetes would worsen the quality of sleep. Both the qualitative and quantitative disturbances in sleep significantly increase the risk of developing diabetes, which is supported by numerous community-based and hospital-based epidemiological studies discussed in this review. Obstructive sleep apnea is one of the most common sleep disorders and is characterized by chronic intermittent hypoxia and increased sympathetic activity, thus leading to a higher prevalence of diabetes. Sleep therapy may serve as a low-cost method for fighting against the rising epidemic of diabetes.