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Small-cell lung cancer (SCLC) transformation from EGFR mutant adenocarcinoma is a rare entity that is considered to be a new phenotype of SCLC. While transformation from adenocarcinoma (ADC) with EGFR exon 19 deletions and exon 21 L858R point mutations has been described, to our knowledge, no cases of transformation to SCLC from exon-18-mutated ADC have been reported. We reported a clinical case of a patient with exon-18-EGFR-transformed SCLC, and we performed a systematic review of the literature.

NR+ is a highly effective vitamin B3 type supplement due to its unique ability to replenish NAD+ levels. While NR+ chloride is already on the market as a nutritional supplement, its synthesis is challenging, expensive, and low yielding, making it cumbersome for large-scale industrial production. Here we report the novel crystalline NR+ salts, d/l/dl-hydrogen tartrate and d/l/dl-hydrogen malate. Their high-yielding, one-pot manufacture does not require specific equipment and is suitable for multi-ton scale production. These new NR+ salts seem ideal for nutritional applications due to their bio-equivalence compared to the approved NR+ chloride. In addition, the crystal structures of all stereoisomers of NR+ hydrogen tartrate and NR+ hydrogen malate and a comparison to the known NR+ halogenides are presented.

The ability to detect, identify and quantify bacteria is crucial in clinical diagnostics, environmental testing, food security settings and in microbiology research. Recently, the threat of multidrug-resistant bacterial pathogens pushed the global scientific community to develop fast, reliable, specific and affordable methods to detect bacterial species. The use of synthetically modified enzyme substrates is a convenient approach to detect bacteria in a specific, economic and rapid manner. The method is based on the use of specific enzyme substrates for a given bacterial marker enzyme, conjugated to a signalogenic moiety. Following enzymatic reaction, the signalophor is released from the synthetic substrate, generating a specific and measurable signal. Several types of signalophors have been described and are defined by the type of signal they generate, such as chromogenic, fluorogenic, luminogenic, electrogenic and redox. Signalophors are further subdivided into groups based on their solubility in water, which is key in defining their application on solid or liquid media for bacterial culturing. This comprehensive review describes synthetic enzyme substrates and their applications for bacterial detection, showing their mechanism of action and their synthetic routes.

Background: This work is part of the regional research project PIPER—Intelligent Platform for the Optimization of Recycling Operations, which aims to develop a network design model for waste collection in the metropolitan city of Rome, Italy. The goal is to enhance the strategic planning of treatment and disposal facilities by incorporating transshipment locations to improve the efficiency of waste collection. The motivation for this study stems from the stringent targets set by the European Green Deal to achieve near-zero emissions and the critical role of waste management in realizing circular economy practices. Methods: The problem is formulated as a mixed integer linear program (MILP) that includes constraints on vehicle allocation to shifts and driver requirements. An additional feature of the model is its ability to account for vehicle maintenance issues when deployed on consecutive shifts. Results: The model was tested against a real-world case study in Rome and demonstrated significant potential savings, with a reduction in total traveled distance exceeding 10%. The mathematical model was also used for evaluating strategic scenarios in a “what-if” analysis, allowing the municipal collection company to assess location options for depots, waste treatment facilities, and transshipment points, as well as to optimize the fleet composition and driver allocation during work shifts. Conclusions: This study presents a robust tool for strategic planning in waste collection operations, highlighting the benefits of using transshipment locations to improve efficiency. The findings indicate substantial potential for cost savings and operational improvements, making the model a valuable asset for municipal waste management planning.

A good integration of the polymer materials that form a mixed-matrix membrane (MMM) for gas separation is essential to reaching interesting permselective properties. In this work, a porous polymer network (PPN), obtained by combining triptycene and trifluoroacetophenone, has been used as a filler, which was blended with two o-hydroxypolyamides (HPAs) that act as polymer matrices. These polymer matrices have been thermally treated to induce a thermal rearrangement (TR) of the HPAs to polybenzoxazoles (β-TR-PBOs) through a solid-state reaction. For its structural study, various techniques have been proposed that allow us to undertake a morphological investigation into the integration of these materials. To access the internal structure of the MMMs, three different methods were used: a polishing process for the material surface, the partial dissolution of the polymer matrix, or argon plasma etching. The argon plasma technique has not only revealed its potential to visualize the internal structure of these materials; it has also been proven to allow for the transformation of their permselective properties. Force modulation and phase contrast in lift-mode techniques, along with the topographic images obtained via the tapping mode using a scanning probe microscope (SPM), have allowed us to study the distribution of the filler particles and the interaction of the polymer and the filler. The morphological information obtained via SPM, along with that of other more commonly used techniques (SEM, TGA, DSC, FTIR, WASX, gas adsorption, and permeability measurements), has allowed us to postulate the most probable structural configuration in this type of system.

The relationships between gas permeability and free volume fraction, intersegmental distance, and glass transition temperature, are investigated. They are analyzed for He, CO2, O2, CH4, and N2 gases and for five similar polyimides with a wide range of permeabilities, from very low to extremely high ones. It has been established here that there is an exponential relationship between permeability and the free volume fraction, and between permeability and the most probable intersegmental distance as measured by WAXS; in both cases, with an exponential coefficient that depends on the kinetic gas diameter as a quadratic polynomial and with a preexponential positive constant. Moreover, it has been proven that the intersegmental distance increases linearly with the free volume fraction. Finally, it has been established that the free volume fraction increases with the glass transition temperature for the polymers tested, and that they depend on each other in an approximate linear way.

Chronic insomnia (insomnia disorder—ID) afflicts up to 10% of the adult population, increases with age and affects more women than men. ID is associated with significant daytime impairments and an increased risk for developing major somatic and mental disorders, especially depression and anxiety disorders. Almost all insomnia models assume persistent hyperarousal on cognitive, emotional, cortical and physiological levels as a central pathophysiological component. The marked discrepancy between only minor objective alterations in polysomnographic parameters of sleep continuity and the profound subjective impairment in patients with insomnia is still puzzling. We and others have proposed that alterations in the microstructure of sleep, especially in REM sleep (REM sleep instability), may explain this discrepancy and be at the core of the experience of fragmented and poor sleep in ID. The REM sleep instability concept is based on evidence showing REM time to be related to subjective wake time in insomnia as well as increased micro- and macro-arousals during REM sleep in insomnia patients compared to good-sleeper controls. Our own work showed that ID patients awoken from REM sleep more frequently reported the perception of having been awake than good sleepers as well as having had more negative ideations. The continuous measurement of event-related potentials throughout the whole night demonstrated reduced P2 amplitudes specifically during phasic REM sleep in insomnia, which points to a mismatch negativity in ID reflecting automatic change detection in the auditory system and a concomitant orienting response. REM sleep represents the most highly aroused brain state during sleep and thus might be particularly prone to fragmentation in individuals with persistent hyperarousal, resulting in a more conscious-like wake experience reflecting pre-sleep concerns of patients with ID, i.e., worries about poor sleep and its consequences, thus leading to the subjective over-estimation of nocturnal waking time and the experience of disrupted and non-restorative sleep. Chronic REM sleep instability might also lead to a dysfunction in a ventral emotional neural network, including limbic and paralimbic areas activated during REM sleep. Along with a postulated weakened functioning in a dorsal executive neural network, including frontal and prefrontal areas, this might contribute to emotional and cognitive alterations and an elevated risk of developing depression and anxiety.

Despite countless papers in the field of radioresistance, researchers are still far from clearly understanding the mechanisms triggered in glioblastoma. Cancer stem cells (CSC) are important to the growth and spread of cancer, according to many studies. In addition, more recently, it has been suggested that CSCs have an impact on glioblastoma patients’ prognosis, tumor aggressiveness, and treatment outcomes. In reviewing this new area of biology, we will provide a summary of the most recent research on CSCs and their role in the response to radio-chemotherapy in GB. In this review, we will examine the radiosensitivity of stem cells. Moreover, we summarize the current knowledge of the biomarkers of stemness and evaluate their potential function in the study of radiosensitivity.

Dairy products can be contaminated by parabens and phenolic compounds from a vast variety of sources, such as packaging and manufacturing processes, or livestock through feed and environmental water. A two-step continuous solid-phase extraction (SPE) and purification methodology was developed here for the determination of both types of compounds. In the first step, a sample extract is passed in sequence through an EMR-lipid sorbent and an Oasis PRiME HBL sorbent to remove fat and preconcentrate the analytes for subsequent detection and quantification by UHPLC−MS/MS. This method enabled the determination of 28 parabens and phenolic contaminant with excellent recovery (91–105%) thanks to the SPE sorbent combination used. The proposed method was validated through the determination of the target compounds, and was found to provide low detection limits (1–20 ng/kg) with only slight matrix effects (0–10%). It was used to analyse 32 different samples of dairy products with different packaging materials. Bisphenol A and bisphenol Z were the two phenolic compounds quantified in the largest number of samples, at concentrations over the range of 24–580 ng/kg, which did not exceed the limit set by European regulations. On the other hand, ethylparaben was the paraben found at the highest levels (33–470 ng/kg).

Forward osmosis (FO) has attracted special attention in water and wastewater treatment due to its role in addressing the challenges of water scarcity and contamination. The presence of emerging contaminants in water sources raises concerns regarding their environmental and public health impacts. Conventional wastewater treatment methods cannot effectively remove these contaminants; thus, innovative approaches are required. FO membranes offer a promising solution for wastewater treatment and removal of the contaminants in wastewater. Several factors influence the performance of FO processes, including concentration polarization, membrane fouling, draw solute selection, and reverse salt flux. Therefore, understanding and optimizing these factors are crucial aspects for improving the efficiency and sustainability of the FO process. This review stresses the need for research to explore the potential and challenges of FO membranes to meet municipal wastewater treatment requirements, to optimize the process, to reduce energy consumption, and to promote scalability for potential industrial applications. In conclusion, FO shows promising performance for wastewater treatment, dealing with emerging pollutants and contributing to sustainable practices. By improving the FO process and addressing its challenges, we could contribute to improve the availability of water resources amid the global water scarcity concerns, as well as contribute to the circular economy.

Impedance spectroscopy has been widely used for the study of the electrical properties of membranes for their characterization. The most common use of this technique is the measure of the conductivity of different electrolyte solutions to study the behavior and movement of electrically charged particles inside the pores of membranes. The objective of this investigation was to observe if there is a relation present between the retention that a nanofiltration membrane possesses to certain electrolytic solutions (NaCl, KCl, MgCl2, CaCl2, and Na2SO4) and the parameters that are obtained through IS measurements of the active layer of the membrane. To achieve our objective, different characterization techniques were performed to obtain the permeability, retention, and zeta potential values of a Desal-HL nanofiltration membrane. Impedance spectroscopy measurements were performed when a gradient concentration was present between both sides of the membrane to study the variation that the electrical parameters had with the time evolution.

Sleep changes significantly throughout the human lifespan. Physiological modifications in sleep regulation, in common with many mammals (especially in the circadian rhythms), predispose adolescents to sleep loss until early adulthood. Adolescents are one-sixth of all human beings and are at high risk for mental diseases (particularly mood disorders) and self-injury. This has been attributed to the incredible number of changes occurring in a limited time window that encompasses rapid biological and psychosocial modifications, which predispose teens to at-risk behaviors. Adolescents’ sleep patterns have been investigated as a biunivocal cause for potential damaging conditions, in which insufficient sleep may be both a cause and a consequence of mental health problems. The recent COVID-19 pandemic in particular has made a detrimental contribution to many adolescents’ mental health and sleep quality. In this review, we aim to summarize the knowledge in the field and to explore implications for adolescents’ (and future adults’) mental and physical health, as well as to outline potential strategies of prevention.

Psychological inflexibility is related to depressive symptoms through the ‘ruminative response style’ (RR) and ‘cognitive fusion’ (CF). We aimed at exploring whether university students were more exposed to CF, RR and depressive symptoms because of their intellectual performance than non-university students of the same age. We compared university students (US) (n = 105) vs. non-university students (NUS) (n = 76) through online administration of the ‘Cognitive Fusion Questionnaire’ (CFQ-7), the ‘Depression-Zung Self-Assessment Scale’ (ZSDS) and the ‘Perseverative Thinking Questionnaire’ (PTQ) (study protocol #0077818/2022, approved by the Ethical Committee of the University of Pisa, Italy). University students scored significantly higher than non-university students in the CFQ-7 Total Score (27.5 ± 9.4 vs. 24.4 ± 9.5; p = 0.040), ZSDS Total Score (41.1 ± 7.7 vs. 39.0 ± 7.3; p = 0.031), PTQ Total Score (26.1 ± 13.1 vs. 21.8 ± 13.9; p = 0.029), PTQ ‘Repetitiveness’ (5.3 ± 2.8 vs. 4.5 ± 2.9; p = 0.034), ‘Intrusiveness’ (5.8 ± 3.0 vs. 4.8 ± 3.1; p = 0.046) and ‘Repetitive Negative Thinking capturing mental resources’ (5.0 ± 3.1 vs. 4.0 ± 3.0; p = 0.013) (MANOVA analysis). In a binary logistic regression analysis of US (with ZSDS scores < 44 vs. ≥44 as the dependent variable, and PTQ Total Score and dimensions, CFQ-7 Total Score, age and gender as the covariates), PTQ Total Score predicted the more severe depressive symptomatology (OR = 1.44, 95% CI: 1.017–2.039; p = 0.040). We believe that RR and CF should be specifically targeted through psychoeducational/psychotherapeutic interventions in university students.

An optimized synthesis of the monomer 2,2′3,3′-biphenyltetracarboxylic dianhydride, iBPDA, was performed to obtain high molecular weight polymers. This monomer has a contorted structure that produces a non-linear shape, hindering the packing of the polymer chain. Aromatic polyimides of high molecular weight were obtained by reaction with the commercial diamine 2,2-bis(4-aminophenyl) hexafluoropropane, 6FpDA, which is a very common monomer in gas separation applications. This diamine has hexafluoroisopropylidine groups which introduce rigidity in the chains, hindering efficient packing. The thermal treatment of the polymers processed as dense membranes had two targets: on the one hand, to achieve the complete elimination of the solvent used, which could remain occluded in the polymeric matrix, and on the other hand to ensure the complete cycloimidization of the polymer. A thermal treatment exceeding the glass transition temperature was performed to ensure the maximum degree of imidization at 350 °C. The good mechanical properties of these materials allow for their use in high-pressure gas purification applications. Moreover, models of the polymers exhibited an Arrhenius-like behavior characteristic of secondary relaxations, normally associated with local motions of the molecular chain. The gas productivity of these membranes was high.

Currently, freshwater scarcity is one of the main issues that the world population has to face. To address this issue, new wastewater treatment technologies have been developed such as membrane processes. Among them, due to the energy disadvantages of pressure-driven membrane processes, Forward Osmosis (FO) and Low-Pressure Reverse Osmosis (LPRO) have been introduced as promising alternatives. In this study, the behavior of a 2.3 m2 tubular membrane TFO-D90 when working with municipal wastewater has been studied. Its performances have been evaluated and compared in two operating modes such as FO and LPRO. Parameters such as fouling, flow rates, water flux, draw solution concentration, organic matter concentration, as well as its recovery have been studied. In addition, the biogas production capacity has been evaluated with the concentrated municipal wastewater obtained from each process. The results of this study indicate that the membrane can work in both processes (FO and LPRO) but, from the energy and productivity point of view, FO is considered more appropriate mainly due to its lower fouling level. This research may offer a new point of view on low-energy and energy recovery wastewater treatment and the applicability of FO and LPRO for wastewater concentration.

Copoly(o-hydroxyamide)s (HPA) and copoly(o-hydroxyamide-amide)s (PAA) have been synthesized to be used as continuous phases in mixed matrix membranes (MMMs). These polymeric matrices were blended with different loads (15 and 30 wt.%) of a relatively highly microporous porous polymer network (PPN). SEM images of the manufactured MMMs exhibited good compatibility between the two phases for all the membranes studied, and their mechanical properties have been shown to be good enough even after thermal treatment. The WAX results show that the addition of PPN as a filler up to 30% does not substantially change the intersegmental distance and the polymer packing. It seems that, for all the membranes studied, the free volume that determines gas transport is in the high end of the possible range. This means that gas flow occurs mainly between the microvoids in the polymer matrix around the filler. In general, both HPA- and PAA-based MMMs exhibited a notable improvement in gas permeability, due to the presence of PPN, for all gases tested, with an almost constant selectivity. In summary, although the thermal stability of the PAA is limited by the thermal stability of the polyamide side chain, their mechanical properties were better. The permeability was higher for the PAA membranes before their thermal rearrangement, and these values increased after the addition of moderate amounts of PPN.

A set of thermally rearranged mixed matrix membranes (TR-MMMs) was manufactured and tested for gas separation. These membranes were obtained through the thermal treatment of a precursor MMM with a microporous polymer network and an o-hydroxypolyamide,(HPA) created through a reaction of 2,2-bis(3-amino-4-hydroxyphenyl)-hexafluoropropane (APAF) and 5′-terbutil-m-terfenilo-3,3″-dicarboxylic acid dichloride (tBTmCl). This HPA was blended with different percentages of a porous polymer network (PPN) filler, which produced gas separation MMMs with enhanced gas permeability but with decreased selectivity. The thermal treatment of these MMMs gave membranes with excellent gas separation properties that did not show the selectivity decreasing trend. It was observed that the use of the PPN load brought about a small decrease in the initial mass losses, which were lower for increasing PPN loads. Regarding the glass transition temperature, it was observed that the use of the filler translated to a slightly lower Tg value. When these MMMs and TR-MMMs were compared with the analogous materials created from the isomeric 5′-terbutil-m-terfenilo-4,4″-dicarboxylic acid dichloride (tBTpCl), the permeability was lower for that of tBTmCl, compared with the one from tBTpCl, although selectivity was quite similar. This fact could be attributed to a lower rigidity as roughly confirmed by the segmental length of the polymer chain as studied by WAXS. A model for FFV calculation was proposed and its predictions compared with those evaluated from density measurements assuming a matrix-filler interaction or ideal independence. It turns out that permeability as a function of FFV for TR-MMMs follows an interaction trend, while those not thermally treated follow the non-interaction trend until relatively high PPN loads were reached.

Membrane dialysis is studied as a promising technique for partial dealcoholization of white wines. The performance of three membrane processes applied for the partial dealcoholization of white wines of the Verdejo variety has been studied in the present work. Combination of Nanofiltration with Pervaporation, single step Pervaporation and, finally, Dialysis, have been applied to white wines from same variety and different vintages. The resulting wines have been chemically and sensorially analyzed and results have been compared with initial characteristics of the wines. From the results obtained, we can conclude that all procedures lead to significant alcohol content reduction (2%, 0.9% and 1.23% v/v respectively). Nevertheless, the best procedure consists in the application of Dialysis to the wines which resulted in a reasonable alcohol content reduction while maintaining organoleptic properties (only 14 consumers were able to distinguish the filtered and original wines, with 17 consumers needed to be this differences significant) and consumer acceptability of the original wine. Therefore, membrane dialysis, as a method of partial dealcoholization of white wines, has undoubted advantages over other techniques based on membranes, which must be confirmed in subsequent studies under more industrial conditions. This work represents the first application of Dialysis for the reduction of alcohol content in wines.

Seven months after the launch of a pilot study to screen newborns for Duchenne Muscular Dystrophy (DMD) in New York State, New York City became an epicenter of the coronavirus disease 2019 (COVID-19) pandemic. All in-person research activities were suspended at the study enrollment institutions of Northwell Health and NewYork-Presbyterian Hospitals, and study recruitment was transitioned to 100% remote. Pre-pandemic, all recruitment was in-person with research staff visiting the postpartum patients 1–2 days after delivery to obtain consent. With the onset of pandemic, the multilingual research staff shifted to calling new mothers while they were in the hospital or shortly after discharge, and consent was collected via emailed e-consent links. With return of study staff to the hospitals, a hybrid approach was implemented with in-person recruitment for babies delivered during the weekdays and remote recruitment for babies delivered on weekends and holidays, a cohort not recruited pre-pandemic. There was a drop in the proportion of eligible babies enrolled with the transition to fully remote recruitment from 64% to 38%. In addition, the proportion of babies enrolled after being approached dropped from 91% to 55%. With hybrid recruitment, the proportion of eligible babies enrolled (70%) and approached babies enrolled (84%) returned to pre-pandemic levels. Our experience adapting our study during the COVID-19 pandemic led us to develop new recruitment strategies that we continue to utilize. The lessons learned from this pilot study can serve to help other research studies adapt novel and effective recruitment methods.

Forward osmosis (FO) is a promising technology for the treatment of urban wastewater. FO can produce high-quality effluents and preconcentrate urban wastewater for subsequent anaerobic treatment. This membrane technology makes it possible to eliminate the pollutants present in urban wastewater, which can cause adverse effects in the ecosystem even at low concentrations. In this study, a 0.6 m2 hollow fiber aquaporin forward osmosis membrane was used for the treatment of urban wastewater from the Valladolid wastewater treatment plant (WWTP). A total of 51 Contaminants of Emerging Concern (CECs) were investigated, of which 18 were found in the target urban wastewater. They were quantified, and their ecotoxicological risk impact was evaluated. Different salts with different concentrations were tested as draw solutions to evaluate the membrane performances when working with pretreated urban wastewater. NaCl was found to be the most appropriate salt since it leads to higher permeate fluxes and lower reverse saline fluxes. The membrane can eliminate or significantly reduce the pollutants present in the studied urban wastewater, producing water without ecotoxicological risk or essentially free of pollutants. In all cases, good recovery was achieved, which increased with molecular weight, although chemical and electrostatic interactions also played a role.

Mixed-matrix membranes (MMMs) consisting of an ortho-hydroxy polyamide (HPA) matrix, and variable loads of a porous polymer network (PPN) were thermally treated to induce the transformation of HPA to polybenzoxazole (β-TR-PBO). Two different HPAs were synthesized to be used as a matrix, 6FCl-APAF and tBTpCl-APAF, while the PPN used as a filler was prepared by reacting triptycene and trifluoroacetophenone. The permeability of He, H2, N2, O2, CH4 and CO2 gases through these MMMs are analyzed as a function of the fraction of free volume (FFV) of the membrane and the kinetic diameter of the gas, allowing for the evaluation of the free volume. Thermal rearrangement entails an increase in the FFV. Both before and after thermal rearrangement, the free volume increases with the PPN content very similarly for both polymeric matrices. It is shown that there is a portion of free volume that is inaccessible to permeation (occluded volume), probably due to it being trapped within the filler. In fact, permeability and selectivity change below what could be expected according to densities, when the fraction of occluded volume increases. A higher filler load increases the percentage of inaccessible or trapped free volume, probably due to the increasing agglomeration of the filler. On the other hand, the phenomenon is slightly affected by thermal rearrangement. The fraction of trapped free volume seems to be lower for membranes in which the tBTpCl-APAF is used as a matrix than for those with a 6FCl-APAF matrix, possibly because tBTpCl-APAF could approach the PPN better. The application of an effective medium theory for permeability allowed us to extrapolate for a 100% filler, giving the same value for both thermally rearranged and non-rearranged MMMs. The pure filler could also be extrapolated by assuming the same tendency as in the Robeson’s plots for MMMs with low filler content.

Polycyclic aromatic hydrocarbons (PAHs) have been classified as priority pollutants by the U.S. Environmental Protection Agency (EPA) and the European Commission on the grounds of their carcinogenic, mutagenic and teratogenic properties. Because of their ubiquity in industrial processes and the environment, PAHs can reach milk and dairy products and, eventually, humans. In this work, a new method was developed to detect and quantify sixteen of the EPA’s priority PAHs in commercial milk and dairy products. The method involves liquid–liquid extraction (LLE) followed by semi-automated solid-phase extraction (SPE) to clean up and preconcentrate the analytes prior their detection and quantification by gas chromatography–mass spectrometry (GC–MS). The proposed method provided high precision (relative standard deviation < 11.5%), recoveries of 80–107% and low detection limits (1–200 ng/kg). The method was applied to analyze 30 dairy products, the majority of which contained some PAH at concentrations from 7.1 to 1900 ng/kg. The most-detected analytes were the lighter PAHs (naphthalene, acenaphthylene, fluorene and phenanthrene). None of the samples, however, contained more than four PAHs.

Mixed matrix membranes (MMMs) consisting of a blend of a hydroxypolyamide (HPA) matrix and variable loads of a porous polymer network (PPN) were thermally treated to induce the transformation of HPA to polybenzoxazole (β-TR-PBO). Here, the HPA matrix was a hydroxypolyamide having two hexafluoropropyilidene moieties, 6FCl-APAF, while the PPN was prepared by reacting triptycene (TRP) and trifluoroacetophenone (TFAP) in a superacid solution. The most probable size of the PPN particles was 75 nm with quite large distributions. The resulting membranes were analyzed by SEM and AFM. Up to 30% PPN loads, both SEM and AFM images confirmed quite planar surfaces, at low scale, with limited roughness. Membranes with high hydrogen permeability and good selectivity for the gas pairs H2/CH4 and H2/N2 were obtained. For H2/CO2, selectivity almost vanished after thermal rearrangement. In all cases, their hydrogen permeability increased with increasing loads of PPN until around 30% PPN with ulterior fairly abrupt decreasing of permeability for all gases studied. Thermal rearrangement of the MMMs resulted in higher permeabilities but lower selectivities. For all the membranes and gas pairs studied, the balance of permeability vs. selectivity surpassed the 1991 Robeson’s upper bound, and approached or even exceeded the 2008 line, for MMMs having 30% PPN loads. In all cases, the HPA-MMMs before thermal rearrangement provided good selectivity versus permeability compromise, similar to their thermally rearranged counterparts but in the zone of high selectivity. For H2/CH4, H2/N2, these nonthermally rearranged MMMs approach the 2008 Robeson’s upper bound while H2/CO2 gives selective transport favoring H2 on the 1991 Robeson’s bound. Thus, attending to the energy cost of thermal rearrangement, it could be avoided in some cases especially when high selectivity is the target rather than high permeability.

Ammonia recovery from synthetic and real anaerobic digestates was accomplished using hydrophobic flat sheet membranes operated with H2SO4 solutions to convert ammonia into ammonium sulphate. The influence of the membrane material, flow rate (0.007, 0.015, 0.030 and 0.045 m3 h−1) and pH (7.6, 8.9, 10 and 11) of the digestate on ammonia recovery was investigated. The process was carried out with a flat sheet configuration at a temperature of 35 °C and with a 1 M, or 0.005 M, H2SO4 solution on the other side of the membrane. Polytetrafluoroethylene membranes with a nominal pore radius of 0.22 µm provided ammonia recoveries from synthetic and real digestates of 84.6% ± 1.0% and 71.6% ± 0.3%, respectively, for a membrane area of 8.6 × 10−4 m2 and a reservoir volume of 0.5 L, in 3.5 h with a 1 M H2SO4 solution and a recirculation flow on the feed side of the membrane of 0.030 m3 h−1. NH3 recovery followed first order kinetics and was faster at higher pHs of the H2SO4 solution and recirculation flow rate on the membrane feed side. Fouling resulted in changes in membrane surface morphology and pore size, which were confirmed by Atomic Force Microscopy and Air Displacement Porometry.

Melatonin, the major regulator of the sleep/wake cycle, also plays important physiological and pharmacological roles in the control of neuronal plasticity and neuroprotection. Accordingly, the secretion of this hormone reaches the maximal extent during brain development (childhood-adolescence) while it is greatly reduced during aging, a condition associated to altered sleep pattern and reduced neuronal plasticity. Altogether, these properties of melatonin have allowed us to demonstrate in both experimental models and clinical studies the great chronobiotic efficacy and sleep promoting effects of exogenous melatonin. Thus, the prolonged release formulation of melatonin, present as a drug in the pharmaceutical market, has been recently recommended for the treatment of insomnia in over 55 years old subjects.

Endocrine disrupting chemicals (EDCs) are exogenous substances capable of altering the human hormone system and causing various diseases such as infertility and cancer as a result. In this work, a method for determining twenty-three different EDCs including parabens, alkylphenols, phenylphenols, organophosphorus pesticides, bisphenol A and triclosan in dairy products was developed. Samples are conditioned by addition of acetonitrile containing 1% formic acid, centrifugation and clean-up of the extract by continuous solid-phase extraction. EDCs in the extract are derivatised by heating in a microwave oven and quantified by gas chromatography–mass spectrometry. The proposed method features good limits of detection (6–40 ng/kg) and precision (relative standard deviation < 7.6%); also, it is scarcely subject to matrix effects (1–20%). EDC recoveries from spiked samples ranged from 80 to 108%. The method was used to analyse a total of 33 samples of dairy products including cow, sheep and goat milk, yoghourt, milkshakes, cheese, cream, butter and custard. Bisphenol A was the individual contaminant detected in the greatest number of samples, at concentrations from 180 to 4800 ng/kg. 2-Phenylphenol and ethylparaben were found in more than one-half, at concentrations over the range 130–3500 and 89–4300 ng/kg, respectively. In contrast, alkylphenols, organophosphorus pesticides and triclosan were detected in none.

A hydroxypolyamide (HPA) manufactured from 2,2-bis(3-amino-4-hydroxy phenyl)-hexafluoropropane (APAF) diamine and 5′-terbutyl-m-terphenyl-4,4′′-dicarboxylic acid chloride (tBTpCl), and a copolyimide produced by stochiometric copolymerization of APAF and 4,4′-(hexafluoroisopropylidene) diamine (6FpDA), using the same diacid chloride, were obtained and used as polymeric matrixes in mixed matrix membranes (MMMs) loaded with 20% (w/w) of two porous polymer networks (triptycene-isatin, PPN-1, and triptycene-trifluoroacetophenone, PPN-2). These MMMs, and also the thermally rearranged membranes (TR-MMMs) that underwent a thermal treatment process to convert the o-hydroxypolyamide moieties to polybenzoxazole ones, were characterized, and their gas separation properties evaluated for H2, N2, O2, CH4, and CO2. Both TR process and the addition of PPN increased permeability with minor decreases in selectivity for all gases tested. Excellent results were obtained, in terms of the permeability versus selectivity compromise, for H2/CH4 and H2/N2 separations with membranes approaching the 2008 Robeson’s trade-off line. The best gas separation properties were obtained when PPN-2 was used. Finally, gas permeation was characterized in terms of chain intersegmental distance and fraction of free volume of the membrane along with the kinetic diameters of the permeated gases. The intersegmental distance increased after TR and/or the addition of PPN-2. Permeability followed an exponential dependence with free volume and a quadratic function of the kinetic diameter of the gas.

The course of multiple sclerosis begins with a relapsing-remitting phase, which evolves into a secondarily progressive form over an extremely variable period, depending on many factors, each with a subtle influence. To date, no prognostic factors or risk score have been validated to predict disease course in single individuals. This is increasingly frustrating, since several treatments can prevent relapses and slow progression, even for a long time, although the possible adverse effects are relevant, in particular for the more effective drugs. An early prediction of disease course would allow differentiation of the treatment based on the expected aggressiveness of the disease, reserving high-impact therapies for patients at greater risk. To increase prognostic capacity, approaches based on machine learning (ML) algorithms are being attempted, given the failure of other approaches. Here we review recent studies that have used clinical data, alone or with other types of data, to derive prognostic models. Several algorithms that have been used and compared are described. Although no study has proposed a clinically usable model, knowledge is building up and in the future strong tools are likely to emerge.

The modifications of the ω-side chain have led to the most interesting biological activities of the prostaglandin analogues [...]

The paper proposes an optimal siting and sizing methodology to design an energy storage system (ESS) for railway lines. The scope is to maximize the economic benefits. The problem of the optimal siting and sizing of an ESS is addressed and solved by a software developed by the authors using the particle swarm algorithm, whose objective function is based on the net present value (NPV). The railway line, using a standard working day timetable, has been simulated in order to estimate the power flow between the trains finding the siting and sizing of electrical substations and storage systems suitable for the railway network. Numerical simulations have been performed to test the methodology by assuming a new-generation of high-performance trains on a 3 kV direct current (d.c.) railway line. The solution found represents the best choice from an economic point of view and which allows less energy to be taken from the primary network.

Background and objectives: The efficacy and safety of ustekinumab have been proved in clinical trials. In daily clinical practice, knowing the factors that determine survival differences of biological drugs allows psoriasis treatment to be optimized as a function of patient characteristics. The main objectives of this work are to understand ustekinumab drug survival in patients diagnosed with plaque psoriasis in the Hospital Universitario Central de Asturias (HUCA Dermatology Department, and to identify the predictors of drug discontinuation. Materials and Methods: A retrospective hospital-based study, including data from 148 patients who were receiving ustekinumab (Stelara®) between 1 February 2009 and 30 November 2019, were collected. Survival curves were approximated through the Kaplan–Meier estimator and compared using the log-rank test. Proportional hazard Cox regression models were used for multivariate analyses while both unadjusted and adjusted hazard ratios (HR) were used for summarizing the studied differences. Results: The average duration of the treatment before discontinuation was 47.57 months (SD 32.63 months; median 41 months). The retention rates were 82% (2 years), 66% (5 years), and 58% (8 years). Median survival was 80 months (95% confidence interval. CI 36.9 to 123.01 months). The survival study revealed statistically significant differences between patients with arthritis (log-rank test, p < 0.001) and those who had previously received biological treatment (log-rank test, p = 0.026). The five-year prevalence in patients still under treatment was 80% (those without arthritis) and 54% (arthritis patients). In the multivariate analysis, only the patients with arthritis had a lower rate of drug survival. No statistically significant differences were observed for any of the other comorbidities studied. The first and second most frequent causes of discontinuation were secondary failure and arthritis inefficacy, respectively. Conclusion: Ustekinumab is a biological drug conferring high survival in plaque psoriasis patients. Ustekinumab survival is lower in patients with arthritis.

Aerosol-cloud interactions (ACI) represent one of the most important sources of uncertainties in climate modelling. In this sense, realistic simulations of ACI are needed for a better understanding of the complex interactions between air pollution and the climate system. This work quantifies the added value of including ACI in an online coupled climate/chemistry model (WRF-Chem, 0.44 ∘ horizontal resolution, years 2003 to 2010) in order to assess whether there is an improvement in the representation of aerosol optical depth (AOD). Modelling results for each species have been evaluated against the Copernicus Atmosphere Monitoring Service (CAMS) reanalysis, and AOD at 675 nm has been compared to AERONET data. Results indicate that the improvements of the monthly biases are around 8% for total AOD550 when including ACI, reaching 20% for the monthly bias in AOD550 coming from dust. Moreover, the temporal representation of AOD550 largely improves (increase in the Pearson time correlation coefficients), ranging from 6% to 20% depending on the chemical species considered. The benefits from this improvement overcome the problems derived from the high computational time required in ACI simulations (eight times higher with respect to simulations not including aerosol-cloud interactions).

A commercial ultrafiltration (UF) membrane (HFM-183 de Koch Membrane Systems) made of poly(vinylidene fluoride) (PVDF), was recovered with a negatively-charged polyelectrolyte (poly(sodium 4-styrenesulfonate)) (PSS), and the effects on its electric, chemical, and morphological properties were analyzed. Atomic force microscopy (AFM), liquid−liquid displacement porometry, Electrical Impedance Spectroscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy were used to investigate the modifications induced by the deposition of PSS on the PVDF positively-charged membrane and after its treatment by a radio frequency Ar-plasma. These techniques confirmed a real deposition and posterior compaction of PSS with increasing roughness and decreasing pore sizes. The evolution of the electric resistances of the membranes confirmed crosslinking and compaction with shielding of the sulfonated groups from PSS. In this way, a membrane with a negatively-charged active layer and a pore size which was 60% lower than the original membrane was obtained. The composition of the additive used by manufacturers to modify PVDF to make it positively charged was obtained by different procedures, all of which depended upon the results of X-ray photoelectron spectroscopy, leading to fairly consistent results. This polymer, carrying positive charges, contains quaternary nitrogen, as confirmed by XPS. Moreover, Raman spectroscopy confirmed that PVDF changes from mostly the β to the α phase, which is more stable as a substrate for the deposited PSS. The aim of the tested modifications was to increase the retention of divalent anions without reducing permeability.