Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictive risk score for unplanned 30-day rehospitalizations in the French universal health care system based on a medico-administrative database

Background Reducing unplanned rehospitalizations is one of the priorities of health care policies in France and other Western countries. An easy-to-use algorithm for identifying patients at higher risk of rehospitalizations would help clinicians prioritize actions and care concerning discharge transitions. Our objective was to develop a predictive unplanned 30-day all-cause rehospitalization risk score based on the French hospital medico-administrative database. Methods This was a retrospective cohort study of all 2015 discharges from acute-care inpatient hospitalizations in a tertiary-care university center comprising four hospitals. The study endpoint was unplanned 30-day all-cause rehospitalization via emergency departments, and we collected sociodemographic, clinical, and hospital characteristics based on hospitalization database computed for reimbursement of fees. We derived a predictive rehospitalization risk score using a split-sample design and multivariate logistic regression, and we compared the discriminative properties with the LACE index risk-score. Result Our analysis included 118,650 hospitalizations, of which 4,127 (3.5%) led to rehospitalizations via emergency departments. Variables independently associated with rehospitalization were age, gender, state-funded medical assistance, as well as disease category and severity, Charlson comorbidity index, hospitalization via emergency departments, length of stay (LOS), and previous hospitalizations 6 months before. The predictive rehospitalization risk score yielded satisfactory discriminant properties (C statistic: 0.74) exceeding the LACE index (0.66). Conclusion Our findings indicate that the possibility of unplanned rehospitalization remains high for some patient characteristics, indicating that targeted interventions could be beneficial for patients at the greatest risk. We developed an easy-to-use predictive rehospitalization risk-score of unplanned 30-day all-cause rehospitalizations with satisfactory discriminant properties. Future works should, however, explore if other data from electronic medical records and other databases could improve the accuracy of our predictive rehospitalization risk score based on medico-administrative data.
Hierarchical porous carbon sheets derived on a MgO template for high-performance supercapacitor applications

Carbon-based supercapacitors have attracted considerable academic and practical interest due to their advantages of low cost, high power density, and superior durability. Herein, we report the facile synthesis of hierarchical porous carbon sheets (HPCSs) featuring a high specific surface area (2788 m2 g−1), derived from pyrrole through a combination of MgO template carbonization and KOH activation. The hierarchical pores with the co-existence of micropores and mesopores were obtained in the HPCSs. Benefiting from the high surface area, well-balanced pore size distribution as well as high conductivity, the prepared HPCSs exhibited a high gravimetric specific capacitance of 226.4 F g−1 at a scan rate of 1 mV s−1 in the electrolyte of 1 M H2SO4 in the two-electrode configuration. Moreover, the excellent electrochemical long-cycle stability has been demonstrated by 10 000 cycles of rapid charging–discharging at 10 A g−1 with a capacitance retention of 97.3%. The electrochemical performance clearly indicates the promising potential of using HPCSs as electrode materials for supercapacitors.
False discovery control for penalized variable selections with high-dimensional covariates

Abstract Modern bio-technologies have produced a vast amount of high-throughput data with the number of predictors much exceeding the sample size. Penalized variable selection has emerged as a powerful and efficient dimension reduction tool. However, control of false discoveries (i.e. inclusion of irrelevant variables) for penalized high-dimensional variable selection presents serious challenges. To effectively control the fraction of false discoveries for penalized variable selections, we propose a false discovery controlling procedure. The proposed method is general and flexible, and can work with a broad class of variable selection algorithms, not only for linear regressions, but also for generalized linear models and survival analysis.
Cubosomal based oral tablet for controlled drug delivery of telmisartan: formulation, in-vitro evaluation and in-vivo comparative pharmacokinetic study in rabbits

Abstract A nanoparticulate system; cubosomes has been suggested to support the controlled release of Telmisartan (TEL), a poorly water-soluble medication. Four distinctive formulae were selected according to the results of three estimated responses. The liquid cubosomes were successfully adsorbed onto Aerosil 380 to form granules. The formulae were evaluated for their flow properties. The best granules were compressed into tablets suitable for oral administration. The tablets were evaluated for its performance. The in vivo study of the best selected cubosomal tablets was checked after oral administration in the blood of albino rabbits utilizing an HPLC method. Results revealed that the highest EE was shown in formulae C5 (59.68 ± 1.3). All the prepared formulae had particle size less than 500 nm with PDI < 0.5 and the highest zeta potential results were observed in C5, C7, C9, C11 and C12 (>30 mv). A7 and A9 prepared using Aerosil 380 showed a perfect flowability. After 1 h of dissolution testing, the commercial product showed a 66% drug release while the release of all cubosomal formulae didn’t exceed 35% during the first hour reaching a 85% of the drug released at the end of 24 h. A7 was selected for the in vivo study; Tmax of TEL absorption is increased for cubosomal formula by three folds indicating sustained release pattern. The relative bioavailability is also increased by 2.6 fold. The investigation proposed the rationality of cubosome to figure an effective controlled release tablets to improve its bioavailability and expand its activity.
Multi-year Quantitative Evaluation of Stilbenoids Levels Among Selected Muscadine Grape Cultivars

Stilbenoids such as t-piceid, t-resveratrol, ε-viniferins, and t-pterostilbene can differ significantly among grape cultivars and years due to variation in environmental conditions and subsequent stressors encountered during a year. This study evaluated diverse muscadine grape cultivars for their ability to consistently produce four major stilbenoids such as t-piceid, t-resveratrol, ε-viniferins, and t-pterostilbene irrespective of environmental changes that can impact their production. Berries from forty-two muscadine grape cultivars were collected for three years (2013, 2014, and 2015) to measure stilbenoids. Results showed significant differences in the composition of four stilbenoids among the muscadine cultivars. The highest level of stilbenoids was observed in ‘Fry Seedless’ (270.20 µg/g fresh weight) in each of the three consecutive years tested followed by ‘Pride’ (46.18 µg/g fresh weight) while ‘Doreen’ produced the lowest level of stilbenoids (1.73 µg/g fresh weight). Results demonstrated that certain muscadine grape cultivars consistently produced varied levels of the four major stilbenoids year after year. Based on the total content of stilbenoids, the 42 muscadine cultivars studied were grouped into three categories such as High, Medium and Low stilbenoid-containing cultivars. This information will help establish new vineyards with cultivars that are less prone to variations in environmental conditions and can consistently produce stilbenoid-rich muscadine grape berries with enhanced market value to promote consumer health.
Gamma-Tocotrienol Induces Apoptosis in Prostate Cancer Cells by Targeting the Ang-1/Tie-2 Signalling Pathway

Emerging evidence suggests that gamma-tocotrienol (γ-T3), a vitamin E isomer, has potent anti-cancer properties against a wide-range of cancers. γ-T3 not only inhibited the growth and survival of cancer cells in vitro, but also suppressed angiogenesis and tumour metastasis under in vivo conditions. Recently, γ-T3 was found to target cancer stem cells (CSCs), leading to suppression of tumour formation and chemosensitisation. Despite its promising anti-cancer potential, the exact mechanisms responsible for the effects of γ-T3 are still largely unknown. Here, we report the identification of Ang-1 (Angiopoietin-1)/Tie-2 as a novel γ-T3 downstream target. In prostate cancer cells, γ-T3 treatment leads to the suppression of Ang-1 at both the mRNA transcript and protein levels. Supplementing the cells with Ang-1 was found to protect them against the anti-CSC effect of γ-T3. Intriguingly, inactivation of Tie-2, a member receptor that mediates the effect of Ang-1, was found to significantly enhance the cytotoxic effect of γ-T3 through activation of AMP-activated protein kinase (AMPK) and subsequent interruption of autophagy. Our results highlighted the therapeutic potential of using γ-T3 in combination with a Tie-2 inhibitor to treat advanced prostate cancer.
NADH-GOGAT Overexpression Does Not Improve Maize (Zea mays L.) Performance Even When Pyramiding with NAD-IDH, GDH and GS

Maize plants overexpressing NADH-GOGAT were produced in order to determine if boosting 2-Oxoglurate production used as a carbon skeleton for the biosynthesis of amino acids will improve plant biomass and kernel production. The NADH-GOGAT enzyme recycles glutamate and incorporates carbon skeletons into the ammonium assimilation pathway using the organic acid 2-Oxoglutarate as a substrate. Gene pyramiding was then conducted with NAD-IDH and NADH-GDH, two enzymes also involved in the synthesis of 2-Oxoglurate. NADH-GOGAT overexpression was detrimental for shoot biomass production but did not markedly affect kernel yield. Additional NAD-IDH and NADH-GDH activity did not improve plant performance. A decrease in kernel production was observed when NADH-GDH was pyramided to NADH-GOGAT and NAD-IDH. This decrease could not be restored even when additional cytosolic GS activity was present in the plants overexpressing the three enzymes producing 2-Oxoglutarate. Detailed leaf metabolic profiling of the different transgenic plants revealed that the NADH-GOGAT over-expressors were characterized by an accumulation of amino acids derived from glutamate and a decrease in the amount of carbohydrates further used to provide carbon skeletons for its synthesis. The study suggests that 2-Oxoglutarate synthesis is a key element acting at the interface of carbohydrate and amino acid metabolism and that its accumulation induces an imbalance of primary carbon and nitrogen metabolism that is detrimental for maize productivity.
Mass spectrometry‐based analysis of macromolecular complexes of Staphylococcus aureus uracil‐DNA glycosylase and its inhibitor reveals specific variations due to naturally occurring mutations

The base excision repair pathway plays an important role in correcting damage induced by either physiological or external effects. This repair pathway removes incorrect bases from the DNA. The uracil base is among the most frequently occurring erroneous bases in DNA, and is cut out from the phosphodiester backbone via the catalytic action of uracil‐DNA glycosylase. Uracil excision repair is an evolutionarily highly conserved pathway and can be specifically inhibited by a protein inhibitor of uracil‐DNA glycosylase. Interestingly, both uracil‐DNA glycosylase (Staphylococcus aureus uracil‐DNA glycosylase; SAUDG) and its inhibitor (S. aureus uracil‐DNA glycosylase inhibitor; SAUGI) are present in the staphylococcal cell. The interaction of these two proteins effectively decreases the efficiency of uracil‐DNA excision repair. The physiological relevance of this complexation has not yet been addressed in detailed; however, numerous mutations have been identified within SAUGI. Here, we investigated whether these mutations drastically perturb the interaction with SAUDG. To perform quantitative analysis of the macromolecular interactions, we applied native mass spectrometry and demonstrated that this is a highly efficient and specific method for determination of dissociation constants. Our results indicate that several naturally occurring mutations of SAUGI do indeed lead to appreciable changes in the dissociation constants for complex formation. However, all of these Kd values remain in the nanomolar range and therefore the association of these two proteins is preserved. We conclude that complexation is most likely preserved even with the naturally occurring mutant uracil‐DNA glycosylase inhibitor proteins.
A Tablet Based Embodied Conversational Agent to Promote Smoking Cessation among Veterans: A Feasibility Study

Embodied Conversational Agent (ECA) offer a new means to support smokers as a virtual coach and motivate them to quit smoking. In this study we assess the feasibility and acceptability of an ECA to support quit smoking (“aka ECA-Q”). ECA-Q, a 14-days program, delivered through Tablet computers, interacts with participants with supporting messages for quit smoking and motivates them to set a quit date. Study participants (n = 6) were Veterans receiving medical care at Boston VA Healthcare System who responded to an open advertisement. Participants completed a survey at baseline and after 14 days follow-up. All participants were satisfied with the ECA program and liked the features of the agent; three out of six participants had set a quit date by the end of the 14 days. Participants reported several positive and less important features of the agent and made suggestions to improve the agent. This study shows that a conversation agent is acceptable to smoking veterans to help them in setting a quit date with an ultimate goal of quit smoking. Insights gained from this study would be useful to redesign the current version of ECA-Q program for a future randomized controlled trial to test the efficacy.
Mode Seeking Generative Adversarial Networks for Diverse Image Synthesis

Most conditional generation tasks expect diverse outputs given a single conditional context. However, conditional generative adversarial networks (cGANs) often focus on the prior conditional information and ignore the input noise vectors, which contribute to the output variations. Recent attempts to resolve the mode collapse issue for cGANs are usually task-specific and computationally expensive. In this work, we propose a simple yet effective regularization term to address the mode collapse issue for cGANs. The proposed method explicitly maximizes the ratio of the distance between generated images with respect to the corresponding latent codes, thus encouraging the generators to explore more minor modes during training. This mode seeking regularization term is readily applicable to various conditional generation tasks without imposing training overhead or modifying the original network structures. We validate the proposed algorithm on three conditional image synthesis tasks including categorical generation, image-to-image translation, and text-to-image synthesis with different baseline models. Both qualitative and quantitative results demonstrate the effectiveness of the proposed regularization method for improving diversity without loss of quality.
The Effects of β-Lactam Antibiotics on Surface Modifications of Multidrug-Resistant Escherichia coli: A Multiscale Approach

Abstract Possible multidrug-resistant (MDR) mechanisms of four resistant strains of Escherichia coli to a model β-lactam, ampicillin, were investigated using contact angle measurements of wettability, crystal violet assays of permeability, biofilm formation, fluorescence imaging, and nanoscale analyses of dimensions, adherence, and roughness. Upon exposure to ampicillin, one of the resistant strains, E. coli A5, changed its phenotype from elliptical to spherical, maintained its roughness and biofilm formation abilities, decreased its length and surface area, maintained its cell wall integrity, increased its hydrophobicity, and decreased its nanoscale adhesion to a model surface of silicon nitride. Such modifications are suggested to allow these cells to conserve energy during metabolic dormancy. In comparison, resistant strains E. coli D4, A9, and H5 elongated their cells, increased their roughness, increased their nanoscale adhesion forces, became more hydrophilic, and increased their biofilm formation upon exposure to ampicillin. These results suggest that these strains resisted ampicillin through biofilm formation that possibly introduces diffusion limitations to antibiotics. Investigations of how MDR bacterial cells modify their surfaces in response to antibiotics can guide research efforts aimed at designing more effective antibiotics and new treatment strategies for MDR bacterial infections.
Docosahexaenoic Acid Inhibits Proliferation of EoL-1 Leukemia Cells and Induces Cell Cycle Arrest and Cell Differentiation

Τhe effect of docosahexaenoic acid (DHA, an omega-3 polyunsaturated fatty acid) upon the proliferation of EoL-1 (Eosinophilic leukemia) cell line was assessed, while additional cellular events during the antiproliferative action were recorded. DHA inhibited EoL-1 cells growth dose-dependently by inducing growth arrest at G0/1 phase of the cell cycle. After DHA addition to the cells, the expression of MYC oncogene was decreased, PTAFR-mRNA overexpression was observed which was used as a marker of differentiation, and PLA2G4A-mRNA increase was recorded. The enzymatic activities of phospholipase A2 (PLA2), a group of hydrolytic enzymes, whose action precedes and leads to PAF biosynthesis through the remodeling pathway, as well as platelet activating factor acetylhydrolase (PAFAH) which hydrolyses and deactivates PAF, were also measured. DHA had an effect on the levels of both the intracellular and secreted activities of PLA2 and PAFAH. The inflammatory cytokines IL-6 and TNF-α were also detected in high levels. In conclusion, DHA-induced EoL-1 cells differentiation was correlated with downregulation of MYC oncogene, overexpression of PTAFR and PLA2G4A-mRNAs, increase of the inflammatory cytokines production, and alteration of the enzymatic activities that regulate PAF levels. DHA is a natural substance and the understanding of its action on EoL-1 cells on molecular level could be useful in further investigation as a future therapeutic tool against F/P + hypereosinophilic syndrome.
The Position of Inhaled Chemotherapy in the Care of Patients with Lung Tumors: Clinical Feasibility and Indications According to Recent Pharmaceutical Progresses

Despite new treatment modalities, including targeted therapies and checkpoint inhibitors, cytotoxic chemotherapy remains central in the care of patients with lung tumors. Use of the pulmonary route to deliver chemotherapy has been proved to be feasible and safe in phase I, Ib/IIa and II trials for lung tumors, with the administration of drug doses to the lungs without prior distribution in the organism. The severe systemic toxicities commonly observed with conventional systemic chemotherapy are consequently reduced. However, development has failed in phase II at best. This review first focuses on the causes of failure of inhaled chemotherapy. It then presents new promising technologies able to take up the current challenges. These technologies include the use of a dry powder inhaler or a smart nebulizer with advanced drug formulations such as controlled-release formulations and nanomedicine. Finally, the potential position of inhaled chemotherapy in patient care is discussed and some indications are proposed based on the literature.
Prebiotic Iron Originates the Peptidyl Transfer Origin

Abstract The ribosome is responsible for protein synthesis in all living organisms. It is best known to exist around 3.5–3.7 Ga whereat life on Earth inhabited anoxic environment with abundant soluble irons. The RNAs and proteins are the two biopolymers that constitute the ribosome. However, both proteins and RNAs require metal cations to fold and to function. There are four Mg-microcluster (Mg2+-μc) structures conserved in core of large subunit, and the 23S ribosomal RNA (rRNA) was shown to catalyze electron transfer in an anoxic environment in the presence of Fe2+. The Mg2+-μc features two idiosyncratic Mg2+ ions that are chelated and bridged by a common phosphate group and along with that, the adjacent residues of RNA backbone together forming ten-membered chelation ring(s). Here, we utilized four rRNA fragments of the large subunit 23S rRNA of Haloarcula marismortui, that includes the residues that form the four Mg2+-μc’s. These four rRNA fragments are shown competent to assemble with Mg2+. Our results show that when these rRNA fragments fold or assembly in the presence of Fe2+ under anoxic conditions, each Fe2+-microcluster can catalyze electron transfer. We propose that Fe2+-microclusters of the ribosome, which use Fe2+ as a cofactor to regulate electron transfer, are pivotal and primordial and may be an origin in evolution of the ribosome.
Effects of Enteric Environmental Modification by Coffee Components on Neurodegeneration in Rotenone-Treated Mice

Epidemiological studies have shown that coffee consumption decreases the risk of Parkinson’s disease (PD). Caffeic acid (CA) and chlorogenic acid (CGA) are coffee components that have antioxidative properties. Rotenone, a mitochondrial complex I inhibitor, has been used to develop parkinsonian models, because the toxin induces PD-like pathology. Here, we examined the neuroprotective effects of CA and CGA against the rotenone-induced degeneration of central dopaminergic and peripheral enteric neurons. Male C57BL/6J mice were chronically administered rotenone (2.5 mg/kg/day), subcutaneously for four weeks. The animals were orally administered CA or CGA daily for 1 week before rotenone exposure and during the four weeks of rotenone treatment. Administrations of CA or CGA prevented rotenone-induced neurodegeneration of both nigral dopaminergic and intestinal enteric neurons. CA and CGA upregulated the antioxidative molecules, metallothionein (MT)-1,2, in striatal astrocytes of rotenone-injected mice. Primary cultured mesencephalic or enteric cells were pretreated with CA or CGA for 24 h, and then further co-treated with a low dose of rotenone (1–5 nM) for 48 h. The neuroprotective effects and MT upregulation induced by CA and CGA in vivo were reproduced in cultured cells. Our data indicated that intake of coffee components, CA and CGA, enhanced the antioxidative properties of glial cells and prevents rotenone-induced neurodegeneration in both the brain and myenteric plexus.