Miracle-dz/UniFAR-FTUs huggingface dataset:
Application of a Pillared-Layer Zn-Triazolate Metal-Organic Framework in the Dispersive Miniaturized Solid-Phase Extraction of Personal Care Products from Wastewater Samples

The pillared-layer Zn-triazolate metal-organic framework (CIM-81) was synthesized, characterized, and used for the first time as a sorbent in a dispersive micro-solid phase extraction method. The method involves the determination of a variety of personal care products in wastewaters, including four preservatives, four UV-filters, and one disinfectant, in combination with ultra-high performance liquid chromatography and UV detection. The CIM-81 MOF, constructed with an interesting mixed-ligand synthetic strategy, demonstrated a better extraction performance than other widely used MOFs in D-µSPE such as UiO-66, HKUST-1, and MIL-53(Al). The optimization of the method included a screening design followed by a Doehlert design. Optimum conditions required 10 mg of CIM-81 MOF in 10 mL of the aqueous sample at a pH of 5, 1 min of agitation by vortex and 3 min of centrifugation in the extraction step; and 1.2 mL of methanol and 4 min of vortex in the desorption step, followed by filtration, evaporation and reconstitution with 100 µL of the initial chromatographic mobile phase. The entire D-µSPE-UHPLC-UV method presented limits of detection down to 0.5 ng·mL−1; intra-day and inter-day precision values for the lowest concentration level (15 ng·mL−1)-as a relative standard deviation (in %)-lower than 8.7 and 13%, respectively; average relative recovery values of 115%; and enrichment factors ranging from ~3.6 to ~34. The reuse of the CIM-81 material was assessed not only in terms of maintaining the analytical performance but also in terms of its crystalline stability.
High-Throughput Virtual Screening, Molecular Dynamics Simulation, and Enzyme Kinetics Identified ZINC84525623 as a Potential Inhibitor of NDM-1

The bacteria expressing New Delhi Metallo-β-lactamase-1 (NDM-1) can hydrolyze all β-lactam antibiotics including carbapenems, causing multi-drug resistance. The worldwide emergence and dissemination of gene blaNDM-1 (produces NDM-1) in hospital and community settings, rising problems for public health. Indeed, there is an urgent need for NDM-1 inhibitors to manage antibiotic resistance. Here, we have identified novel non-β-lactam ring-containing inhibitors of NDM-1 by applying a high-throughput virtual screening of lead-like subset of ZINC database. The screened compounds were followed for the molecular docking, the molecular dynamics simulation, and then enzyme kinetics assessment. The adopted screening procedure funnels out five novel inhibitors of NDM-1 including ZINC10936382, ZINC30479078, ZINC41493045, ZINC7424911, and ZINC84525623. The molecular mechanics-generalized born surface area and molecular dynamics (MD) simulation showed that ZINC84525623 formed the most stable complex with NDM-1. Furthermore, analyses of the binding pose after MD simulation revealed that ZINC84525623 formed two hydrogen bonds (electrostatic and hydrophobic interaction) with key amino acid residues of the NDM-1 active site. The docking binding free energy and docking binding constant for the ZINC84525623 and NDM-1 interaction were estimated to be −11.234 kcal/mol, and 1.74 × 108 M−1 respectively. Steady-state enzyme kinetics in the presence of ZINC84525623 show the decreased catalytic efficiency (i.e., kcat/Km) of NDM-1 on various antibiotics. The findings of this study would be helpful in identifying novel inhibitors against other β-lactamases from a pool of large databases. Furthermore, the identified inhibitor (ZINC84525623) could be developed as efficient drug candidates.
Influence of residual bone height and sinus width on the outcome of maxillary sinus bone augmentation using anorganic bovine bone

OBJECTIVE To evaluate the influence of the posterior residual bone height and sinus width on the outcome of maxillary sinus bone augmentation using anorganic bovine bone. MATERIAL AND METHODS Bilateral sinus bone augmentation was performed using anorganic bovine bone in 20 patients with residual bone height <2 mm in at least one site on each side. Trephine samples were removed at the implant insertion site 8 months after the grafting procedure, and histological and histomorphometric analyses were performed to examine the relative amount (%) of new bone, anorganic bovine bone, and soft tissue in the grafted area. Based on cone beam computed tomography evaluation, the sites of implant insertion were classified according to sinus width into narrow, average, and wide, and according to residual bone height into ≤2 and >2 mm. RESULTS A total of 146 implants were installed and 103 biopsies were evaluated. New bone formation in sites classified as narrow (69 sites), average (19 sites), and wide (15 sites) was 28.5% ± 9.24, 28.9% ± 8.61, and 30.3% ± 7.80, respectively. The mean posterior maxillary residual bone height was 4.0 ± 2.43 mm, and 26 and 77 sites were classified as ≤2 and >2 mm, respectively. New bone formation was 26.2% ± 9.10 and 29.8% ± 8.67 for residual bone height ≤2 and >2 mm, respectively. The differences were non-significant. CONCLUSIONS Within the limitations of the present study, posterior residual bone height and sinus width were not factors with influence on new bone formation in sinuses grafted exclusively with anorganic bovine bone after 8 months of healing.
Neural correlates of attentional capture by stimuli previously associated with social reward

ABSTRACT Our attention is strongly influenced by reward learning. Stimuli previously associated with monetary reward have been shown to automatically capture attention in both behavioral and neurophysiological studies. Stimuli previously associated with positive social feedback similarly capture attention; however, it is unknown whether such social facilitation of attention relies on similar or dissociable neural systems. Here, we used the value-driven attentional capture paradigm in an fMRI study to identify the neural correlates of attention to stimuli previously associated with social reward. The results reveal learning-dependent priority signals in the contralateral visual cortex, posterior parietal cortex, and caudate tail, similar to studies using monetary reward. An additional priority signal was consistently evident in the right middle frontal gyrus (MFG). Our findings support the notion of a common neural mechanism for directing attention on the basis of selection history that generalizes across different types of reward.
The nutrition transition and the double burden of malnutrition.

Chronic noncommunicable diseases are increasingly frequent in low- and medium-income countries, but problems of malnutrition, such as growth restriction in children or micronutrient deficiencies in both children and adults, persist in these same countries. This double burden of malnutrition and the emergence of chronic diseases such as type 2 diabetes strain healthcare systems and constitute a sometimes unbearable load for the countries concerned, for the government, but also for the individuals affected and their families. This double burden is often associated with the nutrition transition or the progression away from the local traditional diet towards a Westernized diet frequently high in fat, salt, and sugar, with low nutritional density. This transition is attributed to worldwide changes in dietary systems expressed by an increased availability of foodstuffs marketed across the planet, such as vegetable oils, sugars, and refined flours, but also the multiplication of points of sale of food that has been processed, even ultraprocessed. The efforts to battle this scourge must take into account the complexity of the phenomenon and the many factors associated with it. A systemic approach that considers the global forces governing the food systems must be promoted. Actions concerning nutrition must therefore emphasize simultaneously the problems of undernutrition and of overnutrition. WHO labels these interventions "double duty actions. "
The angiotensin‐(1‐7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation

Endothelial cell senescence is a hallmark of vascular aging that predisposes to vascular disease. We aimed to explore the capacity of the renin–angiotensin system (RAS) heptapeptide angiotensin (Ang)‐(1‐7) to counteract human endothelial cell senescence and to identify intracellular pathways mediating its potential protective action. In human umbilical vein endothelial cell (HUVEC) cultures, Ang II promoted cell senescence, as revealed by the enhancement in senescence‐associated galactosidase (SA‐β‐gal+) positive staining, total and telomeric DNA damage, adhesion molecule expression, and human mononuclear adhesion to HUVEC monolayers. By activating the G protein‐coupled receptor Mas, Ang‐(1‐7) inhibited the pro‐senescence action of Ang II, but also of a non‐RAS stressor such as the cytokine IL‐1β. Moreover, Ang‐(1‐7) enhanced endothelial klotho levels, while klotho silencing resulted in the loss of the anti‐senescence action of the heptapeptide. Indeed, both Ang‐(1‐7) and recombinant klotho activated the cytoprotective Nrf2/heme oxygenase‐1 (HO‐1) pathway. The HO‐1 inhibitor tin protoporphyrin IX prevented the anti‐senescence action evoked by Ang‐(1‐7) or recombinant klotho. Overall, the present study identifies Ang‐(1‐7) as an anti‐senescence peptide displaying its protective action beyond the RAS by consecutively activating klotho and Nrf2/HO‐1. Ang‐(1‐7) mimetic drugs may thus prove useful to prevent endothelial cell senescence and its related vascular complications.
Posaconazole for the treatment of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis.

OBJECTIVES Allergic bronchopulmonary aspergillosis (ABPA) can accelerate lung function decline in patients with cystic fibrosis (CF). Antifungal medication can be used in addition to systemic corticosteroid treatment. PATIENTS AND METHODS We evaluated Aspergillus-specific IgE and the use of therapeutic drug monitoring of triazoles in a retrospective analysis of 32 patients. RESULTS There was a significant reduction in Aspergillus IgE with posaconazole but not with other triazoles (P = 0.026). Aspergillus IgE levels were inversely correlated with the therapeutic drug level of posaconazole. CONCLUSIONS These data suggest that posaconazole is better than comparator azoles at decreasing serological response to Aspergillus and that this response was better with therapeutic levels of posaconazole.
Modifying release of poorly soluble active pharmaceutical ingredients with the amine functionalized SBA-16 type mesoporous materials

SBA-16 and two modified SBA-16 type ordered mesoporous silica were used as the carriers for ibuprofen (anti-inflammatory drug) and furosemide (loop diuretic drug). Modification of the solid carrier was prepared with chitosan or N-3[(amino(poly-propylenoxy)]aminopropyltrimethoxysilane. The samples of carriers and carrier-drug loaded materials were characterized by X-ray diffraction, N2 adsorption, Fourier-transform infrared spectroscopy, thermogravimetry, and differential scanning calorimetry. The release profiles of active pharmaceutical ingredients were performed in media with different pH in the USP 2 apparatus as well as in two biorelevant media (fasted state simulated gastric fluid and fasted state small intestinal fluid) in USP 4 apparatus. The loading of active substances into mesoporous materials was performed with modified immersion method. The maximum content of deposited drug in mesoporous material was close to 12.0 and 2.2 wt. % for ibuprofen and furosemide, respectively. After drug adsorption, the reduction of BET surface area, pore volume and pore diameter of non-modified and modified SBA-16 was observed, while the cubic arrays of siliceous matrix were well preserved. The release profiles of ibuprofen and furosemide loaded in mesoporous materials in media with different pH and biorelevant fasted state simulated gastric fluid and fasted state small intestinal fluid showed that the new SBA-16 type materials modify the release profiles of furosemide, increasing the dissolution rate of these substances in the medium at pH 1.2. The cytotoxicity of the materials and permeability of drugs after their loading on SBA-16 materials were evaluated on Caco-2 model. The results of our study showed that mesoporous materials did not exert cytotoxic effects and did not influence on the permeability of both active pharmaceutical ingredients in relation to pure substances.
Frequent germline mutations of HAVCR2 in sporadic subcutaneous panniculitis-like T-cell lymphoma.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of peripheral T-cell lymphoma affecting younger patients and associated with hemophagocytic lymphohistiocytosis. To clarify the molecular pathogenesis of SPTCL, we analyzed paired tumor and germline DNAs from 13 patients by whole-exome sequencing. All cases were Asians and were phenotypically sporadic with no family history of SPTCL. Consistent with a recent report, germline mutations in HAVCR2, encoding T-cell immunoglobulin mucin 3 (TIM3), were identified in 11 of 13 (85%) cases. All mutated cases were primary SPTCL, whereas the 2 cases without mutation were secondary SPTCL associated with underlying diseases, including viral infection and autoimmune disease. Ten patients harbored homozygous p.Y82C mutations, and 1 showed compound heterozygous mutations (p.Y82C and p.T101I). Both missense mutations altered highly conserved residues located in the extracellular immunoglobulin variable-like domain. According to the Genome Aggregation Database of >138 500 general individuals, both mutations were documented with minor allele frequencies < 0.007, indicating remarkable enrichment of these HAVCR2 alleles in SPTCL. SPTCL cells also harbored somatic mutations (6.2 per patient) that are frequently identified in genes associated with epigenetic regulation and signal transduction. In conclusion, individuals harboring biallelic HAVCR2 (TIM3) germline mutations were highly susceptible to sporadic SPTCL, which was also associated with clonal somatic mutations.
The effects of male social environment on sperm phenotype and genome integrity

Sperm function and quality are primary determinants of male reproductive performance and hence fitness. The presence of rival males has been shown to affect ejaculate and sperm traits in a wide range of taxa. However, male physiological conditions may not only affect sperm phenotypic traits but also their genetic and epigenetic signatures, affecting the fitness of the resulting offspring. We investigated the effects of male‐male competition on sperm quality using TUNEL assays and geometric morphometrics in the zebrafish, Danio rerio. We found that the sperm produced by males exposed to high male–male competition had smaller heads but larger midpiece and flagellum than sperm produced by males under low competition. Head and flagella also appeared less sensitive to the osmotic stress induced by activation with water. In addition, more sperm showed signals of DNA damage in ejaculates of males under high competition. These findings suggest that the presence of a rival male may have positive effects on sperm phenotypic traits but negative effects on sperm DNA integrity. Overall, males facing the presence of rival males may produce faster swimming and more competitive sperm but this may come at a cost for the next generation.
Global transcriptional regulation of innate immunity by ATF-7 in C. elegans

The nematode Caenorhabditis elegans has emerged as a genetically tractable animal host in which to study evolutionarily conserved mechanisms of innate immune signaling. We previously showed that the PMK-1 p38 mitogen-activated protein kinase (MAPK) pathway regulates innate immunity of C. elegans through phosphorylation of the CREB/ATF bZIP transcription factor, ATF-7. Here, we have undertaken a genomic analysis of the transcriptional response of C. elegans to infection by Pseudomonas aeruginosa, combining genome-wide expression analysis by RNA-seq with ATF-7 chromatin immunoprecipitation followed by sequencing (ChIP-Seq). We observe that PMK-1-ATF-7 activity regulates a majority of all genes induced by pathogen infection, and observe ATF-7 occupancy in regulatory regions of pathogen-induced genes in a PMK-1-dependent manner. Moreover, functional analysis of a subset of these ATF-7-regulated pathogen-induced target genes supports a direct role for this transcriptional response in host defense. The genome-wide regulation through PMK-1– ATF-7 signaling reveals a striking level of control over the innate immune response to infection through a single transcriptional regulator.
The Interdependence of Tonal and Durational Cues in the Perception of Rhythmic Groups

Abstract This experiment investigated whether rising fundamental frequency (f0) and increased duration are interdependent perceptual cues to rhythmic groups in speech, and whether this depends on listeners’ native language. In a twoalternative forced- choice decision task, listeners had to indicate whether they perceived a 3 + 2 or 2 + 3 grouping in 5- syllable- long series of various digits and letters, in which f0 and duration were manipulated in the second and/or third syllable. The listeners were native speakers of Swiss German, Swiss French, or French. These languages differ from each other in terms of prosodic properties involving f0 and duration. The results demonstrate that rising f0 and increased duration are interdependent cues to rhythmic groups, since the two cues were significantly more effective than one when heard simultaneously, but significantly less effective than one when heard in conflicting positions around the rhythmic- group boundary location. Moreover, listeners’ native language influenced whether f0 or duration was the more effective cue. These findings are important not only for their insight into the perception of prosodic groups in speech, but also because they have implications for current research on speech rhythm.
Effect of 7 Months of Physical Training and Military Routine on the Bone Mass of Young Adults.

INTRODUCTION Physical activity (PA) has a great influence on bone mineral density (BMD) and bone mineral content (BMC), however longitudinal studies that seek to relate bone mass to physical activity are scarce and have a small sample size. The aim of this study was to evaluate and compare the effect of 7 months of military physical training (MPT), impact sports (IS), and swimming in the bone mass of young military adults. MATERIALS AND METHODS A prospective study was conducted with 213 military school students (male and aged 19.2 ± 1.2 years) divided into three groups: MPT (n = 144), IS (n = 56), and Swimming (n = 13). Dual-energy X-ray absorptiometry was used to determine body composition (percentage of fat, fat mass, and fat-free mass) and bone mass (BMD, BMD Z-Score, total BMC, arm BMC, leg BMC, and trunk BMC), at the beginning of the military service and after 7 months of training. RESULTS It was observed a significant increase in BMD, BMD Z-Score, total BMC and BMC of all segments analyzed for all groups (p < 0.01). There was a significantly greater variation in BMD of the IS group in relation to the MPT group (p < 0.01), and in the arm BMC of the MPT group in relation to the IS group (p < 0.05). CONCLUSION After 7 months of training, there were significant increases in BMC and BMD of all the groups evaluated. The bone response was associated with the muscular group used in the physical exercise and the IS group showed greater gain in BMD.
Patient-reported minor adverse events after colonoscopy: a systematic review

Abstract Objective: The purpose of this systematic review was to investigate the incidence and nature of minor adverse events (MAEs) after colonoscopy, and response rates to questionnaires concerning MAEs in patients undergoing colonoscopy. Materials and methods: A systematic literature search was conducted in the databases PubMed and Embase. Predictor variables were patient-reported MAEs after colonoscopy. The outcome was frequency and types of MAEs and the patients’ response rate to questionnaires after colonoscopy. Quality assessment for potential risk of bias and level of evidence was evaluated using the National Health and Medical Research Council guidelines. Results: Seven prospective cohorts were included with a pooled total of 6172 participants. Patients undergoing colonoscopy had a response rate to questionnaires ranging from 64% to 100%, with a mean of 81%. One-third of the patients experienced MAEs, most prominently in the first 1–2 weeks after colonoscopy, and less common at 30 days post colonoscopy. The most frequently reported MAEs were abdominal pain, bloating and abdominal discomfort. Conclusions: In general, patients undergoing colonoscopy have a high response rate to questionnaires about MAEs. MAEs after colonoscopy are commonly seen. High age and score of American Society of Anesthesiologists (ASA) classification, female gender and duration of procedure seem to be associated with a higher risk of MAEs, whereas adequate sedation seems to decreases the risk. MAEs after colonoscopy seems to be underreported in the current literature and the existing evidence is based on inhomogeneous reports. In the current study, it was not possible to conduct a meta-analysis. There is a need for larger scale studies addressing the MAEs patients experience in conjunction with a colonoscopy. Furthermore, the assessment of the MAEs should rely on questionnaires tested for validity, comprehensibility and reliability, to reflect the patient-reported experience of a colonoscopy as precise as possible.
De Novo Molecular Design by Combining Deep Autoencoder Recurrent Neural Networks with Generative Topographic Mapping

Here we show that Generative Topographic Mapping (GTM) can be used to explore the latent space of the SMILES-based autoencoders and generate focused molecular libraries of interest. We have built a sequence-to-sequence neural network with Bidirectional Long Short-Term Memory layers and trained it on the SMILES strings from ChEMBL23. Very high reconstruction rates of the test set molecules were achieved (>98%), which are comparable to the ones reported in related publications. Using GTM, we have visualized the autoencoder latent space on the two-dimensional topographic map. Targeted map zones can be used for generating novel molecular structures by sampling associated latent space points and decoding them to SMILES. The sampling method based on a genetic algorithm was introduced to optimize compound properties "on the fly". The generated focused molecular libraries were shown to contain original and a priori feasible compounds which, pending actual synthesis and testing, showed encouraging behavior in independent structure-based affinity estimation procedures (pharmacophore matching, docking).