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Background: Although sex hormones are recognized to induce immune variations, the effect of hormonal therapy use on immunity is only poorly understood. Here, we quantified how hormonal therapy use affects HIV‐1 immune markers in cis women (CW) and trans women and non‐binary people (TNBP) with HIV. Methods: We considered CD4, CD8 and lymphocyte measurements from cis men (CM), CW and TNBP in the Swiss HIV Cohort Study. We modelled HIV‐1 markers using linear mixed‐effects models with an interaction between 'gender' (CW, TNBP) and 'hormonal therapy use' (yes/no). Models were adjusted on age, ethnicity, education level, time since start of antiretroviral therapy and use of intravenous drugs. We assessed the inflammatory effect of hormonal therapy use in 31 TNBP using serum proteomics measurements of 92 inflammation markers. Results: We included 54 083 measurements from 3092 CW and 83 TNBP, and 147 230 measurements from 8611 CM. Hormonal therapy use increased CD4 count and CD4:CD8 ratio in TNBP more than in CW (pinteraction = 0.02 and 0.007, respectively). TNBP with hormonal therapy use had significantly higher CD4 counts [median = 772 cells/μL, interquartile range (IQR): 520–1006] than without (617 cells/μL, 426–892). This was similar to the effect of CW versus CM on CD4 T cells. Hormonal therapy use did not affect serum protein concentrations in TNBP. Conclusion: This study highlights the potential role of hormonal therapy use in modulating the immune system among other biological and social factors, especially in TNBP with HIV. [ABSTRACT FROM AUTHOR]

This viewpoint analyzes recent experiments in guaranteed income (GI) projects and identifies implementation issues that extend the frontiers of public administration. GI programs provide low‐income individuals with substantial and regular cash with few or no strings or conditions attached and are being used to assist the lower income population, including informal workers who are left out of many government programs. The following implementation issues are discussed as frontiers in current public administration research and theory: (1) increasing the federal role in vertical collaboration; (2) improving data integration across levels of government; and (3) finding new solutions to financial and political sustainability. As GI programs and experiments proliferate, it becomes critical to examine implementation and not just outcomes or impact. [ABSTRACT FROM AUTHOR]

The use of seismic catalogs enhanced through advanced detection techniques improves the understanding of earthquake processes by illuminating the geometry and mechanics of fault systems. In this study, we performed accurate hypocentral locations, source parameters estimation and stress release modeling from catalogs of microseismic sequences nucleating in the complex normal fault system of the Southern Apennines (Italy). The application of advanced location techniques resulted in the relocation of ∼30% of the earthquakes in the enhanced catalogs, with hypocenters clearly identifying local patches on kilometer‐scale structures that feature consistent orientation with the main faults of the area. When mapping the stress change on the fault plane, the inter‐event distance compared to the size of the events suggests that the dominant triggering mechanism within the sequences is static stress transfer. The distribution of events is not isotropic but dominantly aligned along the dip direction. These slip‐dominated lineations could be associated with striations related to fault roughness and could map the boundary between locked and creeping domains in Apulian platform and basement. Plain Language Summary: The development of earthquake detection techniques, based on machine learning or similarity, has allowed an increase in the content of seismic catalogs of more than one order of magnitude. However, how much information can be extracted from these small fractures is still to be understood, especially in complex normal fault systems, such as the Apennine environment in Italy. For seismic sequences in Southern Apennines, we show that only a small portion (about 30%) of events in enhanced catalogs can be further characterized in terms of location and source properties. Nevertheless, the use of comprehensive catalogs allows the illumination of kilometric scale structures at depths between 8 and 15 km, to define mechanisms for seismicity evolution, mainly driven by static stress triggering, and to identify seismicity alignments along the slip direction, that can be associated with fault roughness or delimiting boundaries between locked and creeping regions. Key Points: Accurate earthquake location for enhanced catalogs unveils kilometric scale structures where seismic sequences occur in Southern ApenninesStatic stress transfer drives the evolution of these seismic sequences, with earthquakes dominantly distributed along the dip directionSlip‐dominated alignments of the seismicity could map the fault roughness or the boundary between locked and creeping domains [ABSTRACT FROM AUTHOR]

Introduction: Apheresis practices in the United States (US) have not been comprehensively characterized to date. This study aimed to address this gap by evaluating apheresis therapy through a national survey. Methods: A multi‐institutional survey was conducted between April and July 2023. The survey, comprising 54 questions, focused on institutional demographics, procedures, equipment, staffing, training, and impacts of the Coronavirus Disease 2019 (COVID‐19) pandemic. Responses from 22 institutions, primarily academic medical centers, were analyzed. Results: Therapeutic plasma exchange (TPE) was the most common procedure, followed by hematopoietic progenitor cell collection (HPC‐A) and red blood cell exchange (RCE). CAR‐T cell collections were widespread, with some institutions supporting over 30 protocols concurrently. Most sites used the Spectra Optia Apheresis System, were managed by a transfusion medicine service, and employed internal apheresis providers. Insufficient staffing levels, exacerbated by the COVID‐19 pandemic, were common and most often addressed using overtime. Discussion: The survey highlighted the ubiquity of TPE, expanding cellular collections and staffing challenges. The role of apheresis in supporting cellular therapy, particularly in newly developing cell and gene therapies and clinical trials, was evident. Staffing issues during the pandemic emphasized the need for innovative recruitment strategies. Conclusion: This nationwide survey provides the most comprehensive analysis to date of apheresis practices in large US academic centers. [ABSTRACT FROM AUTHOR]

People alive many years after breast (BC) or colorectal cancer (CRC) diagnoses are increasing. This paper aimed to estimate the indicators of cancer cure and complete prevalence for Italian patients with BC and CRC by stage and age. A total of 31 Italian Cancer Registries (47% of the population) data until 2017 were included. Mixture cure models allowed estimation of net survival (NS); cure fraction (CF); time to cure (TTC, 5‐year conditional NS >95%); cure prevalence (who will not die of cancer); and already cured (prevalent patients living longer than TTC). 2.6% of all Italian women (806,410) were alive in 2018 after BC and 88% will not die of BC. For those diagnosed in 2010, CF was 73%, 99% when diagnosed at stage I, 81% at stage II, and 36% at stages III–IV. For all stages combined, TTC was >10 years under 45 and over 65 years and for women with advanced stages, but ≤1 year for all BC patients at stage I. The proportion of already cured prevalent BC women was 75% (94% at stage I). Prevalent CRC cases were 422,407 (0.7% of the Italian population), 90% will not die of CRC. For CRC patients, CF was 56%, 92% at stage I, 71% at stage II, and 35% at stages III–IV. TTC was ≤10 years for all age groups and stages. Already cured were 59% of all prevalent CRC patients (93% at stage I). Cancer cure indicators by stage may contribute to appropriate follow‐up in the years after diagnosis, thus avoiding patients' discrimination. [ABSTRACT FROM AUTHOR]

This systematic review investigates the diagnostic and prognostic utility of coronary flow reserve (CFR) assessment through echocardiography in patients with left bundle branch block (LBBB), a condition known to complicate the clinical evaluation of coronary artery disease (CAD). The literature search was performed on PubMed, EMBASE, Web of Science, Scopus, and Google Scholar, was guided by PRISMA standards up to March 2024, and yielded six observational studies that met inclusion criteria. These studies involved a diverse population of patients with LBBB, employing echocardiographic protocols to clarify the impact of LBBB on coronary flow dynamics. The findings emphasize the importance of CFR in stratifying cardiovascular risk and guiding clinical decision‐making in patients with LBBB. Pooled results reveal that patients with LBBB and significant left anterior descending (LAD) artery stenosis exhibited a marked decrease in stress‐peak diastolic velocity (MD = ‐19.03 [‐23.58; ‐14.48] cm/s; p <.0001) and CFR (MD = ‐.60 [‐.71; ‐.50]; p <.0001), compared to those without significant LAD lesions, suggesting the efficacy of stress echocardiography CFR assessment in the identification of clinically significant CAD among the LBBB population. This review highlights the clinical relevance of echocardiography CFR assessment as a noninvasive tool for evaluating CAD and stratifying risk in the presence of LBBB and underscores the need for standardized protocols in CFR measurement. [ABSTRACT FROM AUTHOR]

The limits of the standard, behaviour‐based clinical assessment of patients with disorders of consciousness (DoC) prompted the employment of functional neuroimaging, neurometabolic, neurophysiological and neurostimulation techniques, to detect brain‐based covert markers of awareness. However, uni‐modal approaches, consisting in employing just one of those techniques, are usually not sufficient to provide an exhaustive exploration of the neural underpinnings of residual awareness. This systematic review aimed at collecting the evidence from studies employing a multimodal approach, that is, combining more instruments to complement DoC diagnosis, prognosis and better investigating their neural correlates. Following the PRISMA guidelines, records from PubMed, EMBASE and Scopus were screened to select peer‐review original articles in which a multi‐modal approach was used for the assessment of adult patients with a diagnosis of DoC. Ninety‐two observational studies and 32 case reports or case series met the inclusion criteria. Results highlighted a diagnostic and prognostic advantage of multi‐modal approaches that involve electroencephalography‐based (EEG‐based) measurements together with neuroimaging or neurometabolic data or with neurostimulation. Multimodal assessment deepened the knowledge on the neural networks underlying consciousness, by showing correlations between the integrity of the default mode network and the different clinical diagnosis of DoC. However, except for studies using transcranial magnetic stimulation combined with electroencephalography, the integration of more than one technique in most of the cases occurs without an a priori‐designed multi‐modal diagnostic approach. Our review supports the feasibility and underlines the advantages of a multimodal approach for the diagnosis, prognosis and for the investigation of neural correlates of DoCs. [ABSTRACT FROM AUTHOR]

Background: Non‐invasive molecular biomarkers for classifying azoospermia by origin into either obstructive or non‐obstructive/secretory azoospermia, as well as for inferring the spermatogenic reserve of the testis of non‐obstructive/secretory azoospermia patients, are of great interest for testicular sperm retrieval outcome prediction for assisted reproduction. Prior analyses of semen small non‐coding RNA expression in azoospermia have focused on microRNAs, but there has been a lack of attention on other regulatory small RNA species. In this regard, studying more in‐depth expression changes of small non‐coding RNA subtypes in small extracellular vesicles from semen of azoospermic individuals could be useful to select additional non‐invasive biomarkers with diagnostic/prognostic purposes. Material and methods: A high‐throughput small RNA profiling analysis to determine the expression pattern of seminal small extracellular vesicle microRNAs (analyzed at the isomiR level), PIWI‐interacting RNAs, and transfer RNA‐derived small RNAs in normozoospermic (n = 4) and azoospermic (obstructive azoospermia because of pathological occurring obstruction in the genital tract, n = 4; secretory azoospermic individuals with positive testicular sperm extraction value, n = 5; secretory azoospermic individuals with negative testicular sperm extraction value, n = 4) individuals was carried out. Reverse transcriptase‐quantitative real‐time polymerase chain reaction validation analysis of selected microRNAs was additionally performed in a larger number of individuals. Results and discussion: Clinically relevant quantitative changes in the small non‐coding RNA levels contained in semen small extracellular vesicles can be used as biomarkers for the origin of azoospermia and for predicting the presence of residual spermatogenesis. In this regard, canonical isoform microRNAs (n = 185) but also other isomiR variants (n = 238) stand out in terms of numbers and fold‐change differences in expression, underlining the need to consider isomiRs when investigating microRNA‐based regulation. Conversely, although transfer RNA‐derived small RNAs are shown in our study to represent a high proportion of small non‐coding RNA sequences in seminal small extracellular vesicle samples, they are not able to discriminate the origin of azoospermia. PIWI‐interacting RNA cluster profiles and individual PIWI‐interacting RNAs with significant differential expression were also not able to discriminate. Our study demonstrated that expression values of individual and/or combined canonical isoform microRNAs (miR‐10a‐5p, miR‐146a‐5p, miR‐31‐5p, miR‐181b‐5p; area under the receiver operating characteristic curve >0.8) in small extracellular vesicles provide considerable clinical value in identifying samples with a high likelihood of sperm retrieval while discriminating azoospermia by origin. Although no individual microRNA showed sufficient discriminating power on its own to identify severe spermatogenic disorders with focal spermatogenesis, multivariate microRNA models in semen small extracellular vesicles have the potential to identify those individuals with residual spermatogenesis. Availability and adoption of such non‐invasive molecular biomarkers would represent a great improvement in reproductive treatment decision protocols for azoospermia in clinical practice. [ABSTRACT FROM AUTHOR]

T‐cell mediated rejection (TCMR), de novo anti‐HLA donor‐specific antibodies (dnDSAs) and ensuing antibody‐mediated rejection (ABMR) reduce kidney transplantation (KT) survival. The immunomodulatory effects of 25‐hydroxyvitamin D [25(OH)D] could be beneficial for KT outcomes. We aimed to evaluating the association between 25(OH)D levels, the development of dnDSAs, clinical TCMR and ABMR, and graft survival. This single center retrospective study included 253 KT recipients (KTRs) transplanted without preformed DSA between 2010 and 2013. We measured 25(OH)D in successive serum samples: at KT (M0) and M12 for the entire cohort, and additionally at M24 and/or M36 when sera were available. We assessed graft outcomes up to 5 years post‐KT. The proportion of KTRs having sufficient 25(OH)D at KT (M0) was high (81.4%) and then dropped at M12 (71.1%). KTRs with sufficient 25(OH)D at M0 experienced less clinical TCMR (HR, 0.41; 95% CI, 0.19–0.88 in multivariate analysis). A sufficient 25(OH)D at M12 was independently associated with a longer dnDSA‐free survival (HR, 0.34; 95% CI, 0.17–0.69). There was no association between 25(OH)D and clinical AMBR. Studying the KTRs with 25(OH)D measurements at M12, M24 and M36 (n = 203), we showed that 25(OH)D sufficiency over the 3 first‐years post‐KT was associated with a longer graft survival in multivariate analyses (HR, 0.39; 95% CI, 0.22–0.70). To our knowledge, this study is the first showing an association between 25(OH)D sufficiency post‐KT and dnDSA occurrence in KTRs. Moreover, we reinforce previously published data showing an association between 25(OH)D, TCMR and graft survival in KT. [ABSTRACT FROM AUTHOR]

Neuroligins are synaptic cell adhesion proteins with a role in synaptic function, implicated in neurodevelopmental disorders. The autism spectrum disorder‐associated substitution Arg451Cys (R451C) in NLGN3 promotes a partial misfolding of the extracellular domain of the protein leading to retention in the endoplasmic reticulum (ER) and the induction of the unfolded protein response (UPR). The reduced trafficking of R451C NLGN3 to the cell surface leads to altered synaptic function and social behavior. A screening in HEK‐293 cells overexpressing NLGN3 of 2662 compounds (FDA‐approved small molecule drug library), led to the identification of several glucocorticoids such as alclometasone dipropionate, desonide, prednisolone sodium phosphate, and dexamethasone (DEX), with the ability to favor the exit of full‐length R451C NLGN3 from the ER. DEX improved the stability of R451C NLGN3 and trafficking to the cell surface, reduced the activation of the UPR, and increased the formation of artificial synapses between HEK‐293 and hippocampal primary neurons. The effect of DEX was validated on a novel model system represented by neural stem progenitor cells and differentiated neurons derived from the R451C NLGN3 knock‐in mouse, expressing the endogenous protein. This work shows a potential rescue strategy for an autism‐linked mutation affecting cell surface trafficking of a synaptic protein. [ABSTRACT FROM AUTHOR]

The performance limitations of traditional computer architectures have led to the rise of brain‐inspired hardware, with optical solutions gaining popularity due to the energy efficiency, high speed, and scalability of linear operations. However, the use of optics to emulate the synaptic activity of neurons has remained a challenge since the integration of nonlinear nodes is power‐hungry and, thus, hard to scale. Neuromorphic wave computing offers a new paradigm for energy‐efficient information processing, building upon transient and passively nonlinear interactions between optical modes in a waveguide. Here, an implementation of this concept is presented using broadband frequency conversion by coherent higher‐order soliton fission in a single‐mode fiber. It is shown that phase encoding on femtosecond pulses at the input, alongside frequency selection and weighting at the system output, makes transient spectro‐temporal system states interpretable and allows for the energy‐efficient emulation of various digital neural networks. The experiments in a compact, fully fiber‐integrated setup substantiate an anticipated enhancement in computational performance with increasing system nonlinearity. The findings suggest that broadband frequency generation, accessible on‐chip and in‐fiber with off‐the‐shelf components, may challenge the traditional approach to node‐based brain‐inspired hardware design, ultimately leading to energy‐efficient, scalable, and dependable computing with minimal optical hardware requirements. [ABSTRACT FROM AUTHOR]

The next generation of brain–machine interfaces are envisioned to couple signal transduction, filtering, and sorting on board with minimum power consumption and maximum bio‐integrability. These functional needs shall be mandatorily met in order to design efficient closed‐loop brain–machine interfaces aimed at treating and monitoring various disorders of the central and peripheral nervous system. Here, the pivotal role is highlighted that organic bioelectronics may have in the contextual development of all these three desiderata, by demonstrating a modular organic‐electronics circuit toward real‐time signal filtering. The inherent filtering capabilities of electrolyte‐gated organic transistor are tuned via adjustment of operational conditions and benchmarked in an electromyography experiment. Additionally, a whole‐organic signal processing circuitry is presented, coupling such transistors with ad hoc designed organic passive components. This provides the possibility to sort complex signals into their constitutive frequency components in real time, thereby delineating innovative strategies to devise organic‐based functional building‐blocks for brain–machine interfaces. [ABSTRACT FROM AUTHOR]

Introduction: Suicide is one of the leading causes of death, with a trend for its increase in Brazil in past decades. This study aimed to review the characteristics of suicides in Brazilian postmortem studies. Methods: Studies investigating suicide deaths in Brazil, and based on autopsy or psychological autopsy were included. Proportions were pooled across studies with the use of random and fixed effects models. Results: 6777 references were retrieved from six databases (searches up to January, 2023), and 45 studies included. In autopsy studies (k = 37, n = 16,231), substance use at toxicological analysis was found in 36.42% of cases (95% CI: 30.05–43.32), previous suicide attempts in 23.92% (95% CI: 6.73–57.78). In psychological autopsy studies (k = 8, n = 139), previous suicide attempts were reported in 28.09% (95% CI: 19.74–38.28), psychiatric conditions/symptoms in 90.67% (95% CI: 67.79–97.82), family history of suicidality in 21.33% (95% CI: 13.5–32.03). Most suicide deaths were reported in males and took place at the victim's home, hanging was the most frequent suicide method. Included studies presented significant limitations in quality assessment. Conclusion: Future studies should present more robust methodology, including bigger samples, the use of controls, and validated methodology. [ABSTRACT FROM AUTHOR]

In this study, we compared the genomes of three metal‐resistant bacteria isolated from mercury‐contaminated soil. We identified diverse and novel MGEs with evidence of multiple LGT events shaping their genomic structure and heavy metal resistance. Among the three metal‐resistant strains, Sphingobium sp SA2 and Sphingopyxis sp SE2 were resistant to multiple metals including mercury, cadmium, copper, zinc and lead. Pseudoxanthomonas sp SE1 showed resistance to mercury only. Whole genome sequencing by Illumina and Oxford Nanopore technologies was undertaken to obtain comprehensive genomic data. The Sphingobium and Sphingopyxis strains contained multiple chromosomes and plasmids, whereas the Pseudoxanthomonas strain contained one circular chromosome. Consistent with their metal resistance profiles, the strains of Sphingobium and Sphingopyxis contained a higher quantity of diverse metal resistance genes across their chromosomes and plasmids compared to the single‐metal resistant Pseudoxanthomonas SE1. In all three strains, metal resistance genes were principally associated with various novel MGEs including genomic islands (GIs), integrative conjugative elements (ICEs), transposons, insertion sequences (IS), recombinase in trio (RIT) elements and group II introns, indicating their importance in facilitating metal resistance adaptation in a contaminated environment. In the Pseudoxanthomonas strain, metal resistance regions were largely situated on a GI. The chromosomes of the strains of Sphingobium and Sphingopyxis contained multiple metal resistance regions, which were likely acquired by several GIs, ICEs, numerous IS elements, several Tn3 family transposons and RIT elements. Two of the plasmids of Sphingobium were impacted by Tn3 family transposons and ISs likely integrating metal resistance genes. The two plasmids of Sphingopyxis harboured transposons, IS elements, an RIT element and a group II intron. This study provides a comprehensive annotation of complex genomic regions of metal resistance associated with novel MGEs. It highlights the critical importance of LGT in the evolution of metal resistance of bacteria in contaminated environments. [ABSTRACT FROM AUTHOR]

Space‐time analysis of mortality risk is useful to evaluate the epidemiologic transitions at the subnational level. In our study, we analysed the death certificate records for lung cancer in Italy in 1995‐2016, obtained from the Italian National Institute of Statistics. Our objective was to investigate the spatial‐temporal evolution of lung cancer mortality by sex and province of residence (n = 107) using the birth cohort as relevant time axis. We built Bayesian space‐time models with space‐time interactions. Among males (n = 554 829), mortality peaked in the 1920‐1929 cohort, followed by a generalised decline. Among females (n = 158 619), we found novel original evidence for a peak in the 1955‐1964 cohort, equivalent to a 35‐year delay, with a downward trend being observed thereafter. Over time, the documented north‐south decreasing mortality gradient has been replaced by a west‐east decreasing gradient. Naples has become the province at highest risk in Italy, both among males and females. This pattern is consistent with an epidemiologic transition of risk factors for lung cancer to the south‐west of the country and raises concern, because 5‐year age‐standardised net survival from the disease in this geographic area is lower than in northern and central Italy. The variability of mortality rates among provinces has changed over time, with an increasing homogeneity for males and an opposite trend for females in the more recent birth cohorts. These unprecedented observations provide evidence for a profound spatio‐temporal transition of lung cancer mortality in Italy. [ABSTRACT FROM AUTHOR]

The global population of Dicotyles tajacu (Linnaeus, 1758) (Cetartiodactyla: Tayassuidae), commonly known as the collared peccary and distributed in the Neotropics, is currently in decline due to anthropogenic pressures. In this study, five microsatellite loci were used to genetically characterize a group of 20 captive‐born collared peccaries intended for reintroduction. This study aimed to evaluate the genetic diversity and relatedness of captive individuals using microsatellite markers. The genetic data generated were used to evaluate the viability of the reintroduction and to propose measures for the management and conservation of this species. In this study, we found relatively high genetic diversity indices, indicating that the group was genetically diverse. Inbreeding coefficients with negative values were observed, indicating an excess of alleles in heterozygosis and an absence of inbreeding. One locus showed deviation from Hardy–Weinberg equilibrium, which may have been caused by the mixing of individuals from different origins. Relatedness analysis indicated that some individuals were highly related, with coefficients indicating they may be first‐degree relatives. Our findings indicate that the studied group has enough genetic diversity to be released into nature, but the high individual relatedness found would require the adoption of strategies after the release of animals in the wild to ensure their persistence. Highlights: The captive group of collared peccaries showed relatively high genetic diversity indices, indicating that the group was genetically diverse.Inbreeding coefficients with negative values were observed, indicating an excess of alleles in heterozygosis and an absence of inbreeding.Our findings indicate that the studied group has enough genetic diversity to be released into nature. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic is still a continuing worldwide challenge for public health systems. Early and ultrasensitive identification of the infection is essential for preventing the spread of COVID‐19 by pre‐symptomatic or asymptomatic individuals, particularly in the community and in‐home settings. This work presents a versatile photoelectrochemical (PEC) immunosensor for SARS‐CoV‐2 detection based on a composite material formed by bismuth vanadate (BiVO4) and strontium titanate (SrTiO3). The PEC platform was denoted as BiVO4/SrTiO3/FTO, and it can be tuned for the detection of either Spike (S) or Nucleocapsid (N) protein by simply altering the antibody immobilized on the platform's surface. Chemical, morphological, and electrochemical characterizations were performed by X‐Ray Diffraction, Scanning Electron microscopy, Energy‐dispersive X‐ray spectroscopy, Electrochemical Impedance Spectroscopy, and Amperometry. With a simple sensing architecture of the PEC platform, it was possible to achieve a linear response range of 0.1 pg mL−1 to 1000 ng mL−1 for S protein and 0.01 pg mL−1 to 1000 ng mL−1 for N protein. The PEC immunosensors presented recovery values for the two SARS‐CoV‐2 proteins in artificial saliva samples between 97 % and 107.20 % suggesting a good accuracy for the proposed immunosensors. [ABSTRACT FROM AUTHOR]

A growth mode of pentacene thin films deposited by high vacuum sublimation where the morphology versus thickness h "rings" back and forth between rough 3D films with pyramid islands and smooth 2D films with ziqqurat islands is discovered. The roughness σ versus h exhibits seamless coherent oscillations whose amplitude and wavelength increase as integer multiples of 1.5 ML thickness. The quantized oscillations are reconducted to dynamic wetting/dewetting transitions involving the upper layers of pentacene film. Importantly, the transconductance of organic field effect transistors, either in solid state or electrolyte‐gated, exhibits antiphase oscillations with one‐decade swing. Charge mobilities in the wetting regime reach 0.1 cm2 V−1 s−1, in line with high‐end values reported for thin‐film pentacene transistors. Controlling this growth mode enables the limitations of charge transport imposed by the roughening transition to be overcome, a universal feature of high vacuum growth to date. [ABSTRACT FROM AUTHOR]

Aims: The current study aims to evaluate the effectiveness of a multidisciplinary diabetic foot team (MDFT) in the management of in‐patients affected by diabetic foot problems. Materials and Methods: The study was a retrospective observational study. Consecutive patients with a diabetic foot problem requiring hospitalisation were included. All patients were managed by a MDFT led by diabetologists according to the guidance. The rate of in‐hospital complications (IHCs), major amputation, and survival were recorded at the end of patient's hospitalisation. IHC was defined as any new infection different from wound infection, cardiovascular events, acute renal injury, severe anaemia requiring blood transfusion, and any other clinical problem not present at the assessment. Results: Overall, 350 patients were included. The mean age was 67.9 ± 12.6 years, 254 (72.6%) were males, 323 (92, 3%) showed Type 2 diabetes with a mean duration of 20.2 ± 9.6 years; 224 (64%) had ischaemic diabetic foot ulcers (DFUs) and 299 (85.4%) had infected DFUs. IHCs were recorded in 30/350 (8.6%) patients. The main reasons for IHCs were anaemia requiring blood transfusion (2.8%), pneumonia (1.7%), acute kidney failure (1.1%). Patients with IHCs showed a higher rate of major amputation (13.3 vs. 3.1%, p = 0.02) and mortality (16.7 vs. 0.6%, p < 0.0001) in comparison to those without. Ischaemic heart disease (IHD) and wound duration at the assessment (>1 month) were independent predictors of IHC, whereas IHCs, heart failure, and dialysis were independent predictors of in‐hospital mortality. Conclusions: The multidisciplinary management of diabetic foot problems leads to an IHC rate of 8%. The risk of IHCs is higher in patients with IHD and long wound duration. [ABSTRACT FROM AUTHOR]

Objective: The term "mood stabilizer" is controversial in the literature and criticized for being imprecise and overly inclusive, having its retirement suggested to avoid misuse. Nevertheless, it continues to be employed as it may still carry important meaning. Methods: We employed document analysis for reviewing relevant definitions of mood stabilizer employed in the literature. Then, we clarify the meanings associated with the term by employing evolutionary concept analysis. Based on its results, we present a theoretical model for a mood stabilizer and further match it with evidence gathered from published meta‐analyses and other sources for drugs used in the treatment of bipolar disorder. Results: Concept analysis unearthed four attributes of a mood stabilizer that were nested into the following ascending hierarchy: "not worsening," "acute effects," "prophylactic effects," and "advanced effects." "Prophylactic effects" were often considered the core aspect of a legitimate mood stabilizer. Conclusion: The proposed model uses a hierarchy of attributes that take into account the complexity of the term and help to determine whether a drug is a mood stabilizer. Prophylaxis is pivotal to the concept, whose utility lies in implying a drug able to truly treat bipolar disorder, as opposed to merely targeting symptoms. Consistent use of the term could encourage investigation of drugs that modify long‐term outcomes and illness trajectory, instead of simply approaching symptom clusters. [ABSTRACT FROM AUTHOR]

In situ magnetic field measurements are often difficult to obtain due to the presence of stray magnetic fields generated by spacecraft electrical subsystems. The conventional solution is to implement strict magnetic cleanliness requirements and place magnetometers on a deployable boom. However, this method is not always feasible on low‐cost platforms due to factors such as increased design complexity, increased cost, and volume limitations. To overcome these problems, we propose using the Quad‐Mag CubeSat magnetometer with an improved Underdetermined Blind Source Separation (UBSS) noise removal algorithm. The Quad‐Mag consists of four magnetometer sensors in a single CubeSat form‐factor card that allows distributed measurements of stray magnetic fields. The UBSS algorithm can remove stray magnetic fields without prior knowledge of the magnitude, orientation, or number of noise sources. UBSS is a two‐stage algorithm that identifies signals through cluster analysis and separates them through compressive sensing. We use UBSS with single‐source point detection to improve the identification of noise signals and iteratively‐weighted compressed sensing to separate noise signals from the ambient magnetic field. Using a mock CubeSat, we demonstrate in the lab that UBSS reduces four noise signals producing more than 100 nT of noise at each magnetometer to below the expected instrument resolution (5 nT at 65 Hz). Additionally, we show that the integrated Quad‐Mag and improved UBSS system works well for 1U, 2U, 3U, and 6U CubeSats in simulation. Our results show that the Quad‐Mag and UBSS noise cancellation package enables high‐fidelity magnetic field measurements from a CubeSat without a boom. Plain Language Summary: Measuring magnetic fields in their natural space environment, or "in situ," can be difficult because of interference from other artificial magnetic fields. These other magnetic fields, called "stray magnetic fields," are often created by the electrical subsystems on the spacecraft. The usual way to solve this problem is by making sure the spacecraft is very clean magnetically and by putting special sensors on a long boom that sticks out from the spacecraft. However, this solution can be difficult to use on small spacecraft, such as CubeSats, because it makes the spacecraft more expensive and harder to design. In this study, we propose an alternative solution by using a special sensor called Quad‐Mag and a method to cancel out noise called Underdetermined Blind Source Separation (UBSS). This new solution allows accurate measurements without the need for a long arm and it works well even on CubeSats. The combination of Quad‐Mag and UBSS technology has the potential to revolutionize CubeSat magnetometry, offering valuable opportunities for space research and exploration. Key Points: The Quad‐Mag CubeSat magnetometer combined with the UBSS noise cancellation technique enable high‐fidelity magnetic field measurements without the need for a boomQuad‐Mag instrument equipped with four magneto‐inductive magnetometers has a resolution two times better than that of any single sensorUBSS algorithm can remove stray magnetic field noise without prior knowledge of the magnitude, orientation, or number of noise sources [ABSTRACT FROM AUTHOR]

To date (5/27/2023) nearly 3 years after the official declaration of the COVID-19 pandemic, a total of 766 895 075 cases and 6 935 889 deaths have been officially reported to the world health organization (WHO) (https://covid19.who.int/). Furthermore, multiple VOC and variants of interest, (VOI), have been identified from these clades, with the clade GRA (phylogenetic clade based on GISAID classification) comprising the VOC omicron, which became dominant in 2022 (Figure 1B). Deciphering the evolutionary mechanisms of SARS-CoV-2: Absence of ORF8 protein and its potential advantage in the emergence of viral lineages (E) Evidence of intensified diversifying selection in the GRA clade (comprising the VOC omicron) in relation with the rest of the clades was obtained by the algorithm RELAX. [Extracted from the article]

Monitoring insects of different species to understand the factors affecting their diversity and decline is a major challenge. Laser remote sensing and spectroscopy offer promising novel solutions to this. Coherent scattering from thin wing membranes also known as wing interference patterns (WIPs) have recently been demonstrated to be species specific. The colors of WIPs arise due to unique fringy spectra, which can be retrieved over long distances. To demonstrate this, a new concept of infrared (950–1650 nm) hyperspectral lidar with 64 spectral bands based on a supercontinuum light source using ray‐tracing and 3D printing is developed. A lidar with an unprecedented number of spectral channels, high signal‐to‐noise ratio, and spatio‐temporal resolution enabling detection of free‐flying insects and their wingbeats. As proof of principle, coherent scatter from a damselfly wing at 87 m distance without averaging (4 ms recording) is retrieved. The fringed signal properties are used to determine an effective wing membrane thickness of 1412 nm with ±4 nm precision matching laboratory recordings of the same wing. Similar signals from free flying insects (2 ms recording) are later recorded. The accuracy and the method's potential are discussed to discriminate species by capturing coherent features from free‐flying insects. [ABSTRACT FROM AUTHOR]

Cortisol is a steroid hormone naturally produced by the adrenal glands. It participates in and controls several processes in the body and is considered an important physiological biomarker. Due to its very low concentrations in body fluids, its detection requires high sensitivity and specificity. Here, we present a simple electrochemical biosensor based on reduced graphene oxide (rGO) modified with gold nanoparticles (AuNPs) for the immobilization of the cortisol‐specific aptamer (Ap) (MCH‐Ap‐AurGO/GCE). Important analytical parameters for identifying the target analyte were optimized, such as conditions and amount of immobilized Ap, the influence of the concentration and nature of the supporting electrolyte, pH of the medium, and incubation time. The optimized conditions for the aptasensor were: concentration of Ap 1.0 × 10−6 mol L−1, support electrolyte Tris/HCl 50 mmol L−1, MgCl2 10 mmol L−1, and NaCl 10 mmol L−1, at pH 5.0 and incubation time of 15 min. A linear response range was obtained from 1 × 10−18 up to 1 × 10−11 mol L−1 of cortisol with a detection limit (LOD) of 1.0 × 10−18 mol L−1. A curve adjusted for operational purposes in the saliva sample was fitted for the concentration range between 0.5 × 10−14 and 1 × 10−11 mol L−1, with a linear regression equation ΔRtc/Rtc1 = 2.70 + 0.17 × log([Cortisol]). The aptasensor demonstrated a great potential for detecting cortisol in a simple, fast, and highly sensitive way, opening its path for application in real samples, which present levels below the concentration in which cortisol is commonly found in body fluids. [ABSTRACT FROM AUTHOR]

Genotype‐by‐environment interaction (GEI) is a major concern in tropical maize breeding. Here, we used factor analytic mixed models (FAMM) to study GEI in a tropical maize dataset. Our goal was to select high‐performance and stable hybrids using factor analytic selection tools (FAST) derived from FAMM outputs. Because the dataset comprised two different planting seasons, we also investigated differences in the genetic gains between seasonal and general selection (i.e., for both seasons simultaneously). The trials were installed in a lattice design with 36 hybrids containing two replicates and blocks with six plants each. We evaluated 53 hybrids and seven checks in 48 environments, represented by a combination of locations, years and seasons. We fitted the FAMMs with distinct sets of factors. The best‐fitted FAMM was selected considering a parsimony‐explained variance balance. Using the best FAMM for both seasonal and general analyses, we estimated the following selection tools: overall performance (OP$\textit{OP}$); root mean square deviation (RMSD$\textit{RMSD}$), which represents general stability; and responsiveness , which represents specific stability. We selected hybrids based on an index built with OP$\textit{OP}$ and RMSD$\textit{RMSD}$. Five and three hybrids were selected considering both general and seasonal analyses for the first and second season, respectively. Two hybrids were amongst the top eight for both seasonal analyses (i.e., only first season and only second season simultaenously). Higher genetic gains may be obtained by employing FAMM and using FAST in each season rather than analysing both seasons in a joint fashion. Core Ideas: Factor analytic selection tools are suitable for recommending maize genotypes in multi‐environment trials.A seasonal selection approach provides higher genetic gains.High‐performance and stable single‐cross hybrids were recommended for tropical conditions. [ABSTRACT FROM AUTHOR]

Inkjet printing is a popular technique for depositing high-precision ink lines. This study reports the printing parameters' influence on the electrical properties of the sensing devices. The electrochemical sensors are fabricated with a commercial piezoelectric printer and silver ink. Different substrates are evaluated in the printing process, including paper, polyimide, and polyvinyl chloride (PVC) tapes. Ink depositions' temperature, ink drop spacing, length, and the number of the ink layer are also evaluated in this study. Higher temperatures (40 °C) make the substrate surface smoother, improving the printing quality. Controlling the ink drop spacing produces narrow continuous ink lines. The number of ink layers changes the film thickness, altering their electroactive surface area. The best printing parameters are PVC tape at 40 °C, 17 µm drop spacing, one layer, and 13 mm length. Under optimized conditions, three-electrode electrochemical systems are fully printed with silver ink, showing batch-to-batch reproducibility (RSD = 3%). Their analytical performance is evaluated for picric acid, hydrogen peroxide, and glucose quantification. The sensors are modified with glucose oxidase to quantify glucose in artificial saliva, confirming their analytical applicability. Therefore, this work reports fundamental aspects of inkjet printing, bringing valuable findings to guide new research involving inkjet-printed electrochemical biosensors/sensors ((bio)sensors). [ABSTRACT FROM AUTHOR]

The study of the ground deformation in active calderas provides valuable indications of the ongoing dynamical processes. In this framework, we analyze the borehole tiltmeter data recorded at Campi Flegrei (Southern Italy) from their first installation (1 April 2015), in order to retrieve the kinematics of the ground deformation and its main anomalies. Our approach involves the nonlinear dynamics analysis aimed at the identification of the degrees of freedom of the system and thus its complexity. Starting from the second part of the year 2020, the behavior of the dynamical system becomes collective, and a locally significant deviation of the deformative pattern from the background trend is observed. In particular, a series of 15 slow tilt variations (like jumps lasting a few days) appears in the ground deformation. They are associated with a very low‐dimensional system likely generated by a local second‐order source. The latter is related to fluid migration and it is superimposed on the primary one located in Pozzuoli town and driving the current uplift of Campi Flegrei. The effects of such a local, second‐order stress field are, indeed, evident in the area of the volcanic dome of Mt. Olibano, where they are measured as tilt steps. The superposition of primary and second‐order sources of deformation acting contemporaneously can justify the recent variations in geophysical and geochemical parameters. Our approach based on the joint dynamical and kinematical analyses of the tiltmeter data can be applied to other volcanic/tectonic areas or extended to other geophysical and geochemical variables. Plain Language Summary: In order to help understand the deformative processes that characterize the bradyseism at Campi Flegrei caldera, we use tiltmeter sensors deployed at various depths in the surveyed area. The tiltmeter network is able to detect slight ground tilt variations of the caldera in both direction and amplitude. In addition to the general uplift of the area recorded since 2005, whose primary source, located in Pozzuoli, generates a radial field, we find some interesting anomalies under kinematics and dynamics profiles. By comparing the ground tilt with seismicity, we notice the greatest release of energy after a large tilt change in July 2018 and, since mid‐September 2020, an increase in the earthquakes' occurrence as well as in the tilt rate. Simultaneously, a second‐order local source overlaps with the primary. In this context, the complex dynamics associated with the volcano becomes more organized and collective. The new approach based on the joint dynamics and kinematics analyses of the tiltmeter data is a powerful tool able to extract features from a complex volcanic region and isolate small signals. Due to its generality, it can be applied to other volcanic/tectonic areas to monitor the background activity or extended to other geophysical and geochemical variables. Key Points: Ground deformation pattern is inferred by tiltmeters analysis at Campi FlegreiNonlinear dynamics analysis identifies the evolution of a complex system that undergoes collective behaviorA deviation from the main source radial deformative pattern in Pozzuoli is observed due to a second‐order local source at Mt Olibano [ABSTRACT FROM AUTHOR]

It has recently been suggested that clay minerals, which are widespread on the Martian surface, could be the possible source of the basal bright reflections detected by MARSIS at Ultimi Scopuli, instead of briny water. This hypothesis is based on dielectric measurements on a wet Ca‐Montorillonite (STx‐1b) sample conducted at 230 K, which reported permittivity values (apparent permittivity of 39 at 4 MHz) compatible with the median value of 33 retrieved by MARSIS 4 MHz data inversion in the high reflectivity area. These experimental results are, however, incompatible with well‐established dielectric theory and with laboratory measurements on clays, at MARSIS frequency and Martian temperatures, reported in the literature. Here, we replicate the experiment using a setup to precisely control the rate of cooling/warming and the temperature inside and outside the clay sample. We found that the rate of cooling, the position of the temperature sensor and, consequently, the thermal equilibrium between the sample and the sensor play a fundamental role in the reliability of the measurements. Our results indicate that even for a large water content in the clay sample, at 230 K and 4 MHz, the apparent permittivity is only 8.4, dropping to 4.1 at 200 K, ruling out clays as a possible source of the bright reflections detected by MARSIS at the base of the SPLD. Plain Language Summary: The recent discovery of bright basal reflections below the South polar ice cap at Ultimi Scopuli (Mars) by MARSIS has sparked an intense debate on their origin. Because bright radar reflections detected below the ice sheets in Antarctica and Greenland usually indicate the presence of basal water, and based on additional data processing methods, these anomalies were interpreted to be caused by liquid briny water. Recent laboratory measurements questioned this hypothesis and instead suggested that the presence of clay could explain the observed results. According to these measurements, the dielectric properties of wet clay at 230 K (−43°C) mimic the high reflectivity of briny water. Here, we replicate the experiment, making sure to reach thermal equilibrium during each measurement run to guarantee that the temperature is correctly evaluated when the dielectric properties of the sample are measured. This was accomplished using a dedicated setup to precisely control the thermal cycle and to carefully check the internal and external temperatures of the wet clay sample. Our experimental results clearly show that the dielectric properties of clay at 230 K are incompatible with the observed MARSIS anomalies and thus briny water remains the most plausible explanation for the bright basal reflections detected by MARSIS. Key Points: Anomalous bright basal reflections have been detected by MARSIS at Ultimi Scopuli, MarsDielectric measurements of wet clays at low temperature show that they cannot generate strong basal reflectionsReliable measurements of dielectric behavior of planetary analogs require a careful control of the temperature inside the sample [ABSTRACT FROM AUTHOR]

Background: The global increase in incidence of cutaneous malignant melanoma (CMM) occurring in the past decades has been partly attributed to increased diagnostic scrutiny of early lesions, with a potential phenomenon of overdiagnosis. The reported positive linear relation between skin biopsy rate and incidence of early CMM is compatible with this hypothesis. Objectives: We explored the ecological association between the trends in annual dermatologic office visit rates, skin biopsy rates, incidence rates of in situ and invasive CMM by tumour thickness category, and CMM mortality rates in the Emilia‐Romagna Region (northern Italy). Methods: Four cancer registries covering a population of 2,696,000 provided CMM incidence data for the years 2003–2017. Dermatologic office visit rates and skin biopsy rates were calculated using the Regional outpatient care database. All rates were age‐standardized. Trends were described with the estimated average annual per cent change (EAAPC). Correlations were tested with the Spearman correlation coefficient. Results: Incidence increased significantly. The increase was steeper for in situ CMM (EAAPC: men, 10.2; women, 6.9) followed by CMM <0.8 mm thick (9.1; 5.2), but the rates grew significantly for most subgroups of CMMs ≥0.8 mm thick. Mortality decreased significantly among women (−2.3) and non‐significantly among men. For dermatologic office visit rate and skin biopsy rate the EAAPC were, respectively, 1.7 and 1.8 for men and 1.2 and 0.9 for women. Annual dermatologic office visit rate correlated with skin biopsy rate in both sexes. However, the proportion of skin biopsies out of dermatologic office visits was constant across the years (range: men, 0.182–0.216; women, 0.157–0.191). Conclusions: In Italy, the increasing CMM incidence trend is, at least in part, genuine. Overdiagnosis—if any—is due to an increased patient presentation at dermatologic offices and not to a lower dermatologic threshold to perform biopsy. [ABSTRACT FROM AUTHOR]

Such hypotheses find additional feedback when patients are asked about deodorants use during a flare-up; only 25% of them used deodorants in such condition, with higher PGA score related to reduced deodorants use ( I p i = 0.037). Deodorant use is similar and frequent in patients with minimal to mild HS, while almost half of the patients scoring HS-PGA 3 stated to not use deodorants. Diode laser and intense pulsed light laser, indeed, showed better outcomes than any other method, with no patients reporting worsening after laser hair removal even if it was used only by 8% of patients. [Extracted from the article]

Introduction: Identifying CSF‐based biomarkers for the β‐amyloidosis that initiates Alzheimer's disease (AD) could provide inexpensive and dynamic tests to distinguish AD from normal aging and predict future cognitive decline. Methods: We developed immunoassays specifically detecting all C‐terminal variants of secreted amyloid β‐protein and identified a novel biomarker, the Aβ 37/42 ratio, that outperforms the canonical Aβ42/40 ratio as a means to evaluate the γ‐secretase activity and brain Aβ accumulation. Results: We show that Aβ 37/42 can distinguish physiological and pathological status in (1) presenilin‐1 mutant vs wild‐type cultured cells, (2) AD vs control brain tissue, and (3) AD versus cognitively normal (CN) subjects in CSF, where 37/42 (AUC 0.9622) outperformed 42/40 (AUC 0.8651) in distinguishing CN from AD. Discussion: We conclude that the Aβ 37/42 ratio sensitively detects presenilin/γ‐secretase dysfunction and better distinguishes CN from AD than Aβ42/40 in CSF. Measuring this novel ratio alongside promising phospho‐tau analytes may provide highly discriminatory fluid biomarkers for AD. [ABSTRACT FROM AUTHOR]

Miniaturized paper‐based electrochemical sensors were fabricated using kraft paper and CO2 laser, dispensing the need for chemical reagents and controlled atmospheric conditions. This study initially evaluated the paper type and laser processing parameters, enhancing the electrodes′ robustness, electrochemical response, and electrical resistance. The sensors were also treated by applying −1 V for 60 s in 1.0 mol L−1 KCl, which is a simple and rapid procedure. The electrochemical treatment increased the electroactive area and roughness, confirmed by scanning electron microscopy. These aspects helped modulate the sensors′ electrochemical response for nitrite determination, improving selectivity and sensitivity for this compound. The sensors also showed repeatability and batch‐to‐batch reproducibility, with 2.2 and 10 % RSD, respectively. Therefore, this work brings a protocol to fabricating competitive electrochemical sensors through a sustainable strategy, opening possibilities for designing new analytical systems. [ABSTRACT FROM AUTHOR]

Over the past few years, the emergence of electrochemical wearable sensors has attracted considerable attention because of their promising application in point‐of‐care testing due to some features such as high sensitivity, simplicity, miniaturization, and low fabrication cost. Recent developments in new fabrication approaches and innovative substrates have resulted in sensors able to real‐time and on‐body measurements. Wearable electrochemical sensors have also been combined with paper‐based substrates and directly used on human skin for different applications for non‐invasive analyses. Furthermore, wearable electrochemical sensors enable monitoring analytes in different biofluids without complex procedures, such as pre‐treatment or sample manipulation. The coupling of IoT to various wearable sensors has also attracted attention due to real‐time data collection and handling in remote and resource‐limited conditions. This mini‐review presents the significant advances in developing wearable electrochemical devices, such as sampling, data collection, connection protocols, and power sources, and discusses some critical challenges for higher performance in this field. We also present an overview of the application of paper as an intelligent substrate for electrochemical wearable sensors and discuss their advantages and drawbacks. Lastly, conclude by highlighting the future advances in wearable sensors and diagnostics by coupling real‐time and on‐body measurements to multiplexed detection of different biomarkers simultaneously, reducing the cost and time of classical analysis to provide fast and complete overall physiological conditions to the wearer. [ABSTRACT FROM AUTHOR]

Herein we have proposed that a redox mechanism can produce surface charges and negative zeta potential on an aqueous graphite dispersion. Graphite was kept in contact with a concentrated ammonia aqueous solution, washed, and exfoliated in water, resulting in a dispersion with lyophobic nature. Ammonia treatment did not provide functional groups or nitrogen doping to graphite. Moreover, this material was washed twice before sonication to remove most hydroxide. Therefore, neither functional groups, nitrogen atoms, nor hydroxide excess is responsible for the zeta potential. Kelvin probe force microscopy has shown that the ammonia‐treated and exfoliated graphite has higher Fermi level than the water‐treated material, indicating that the contact between ammonia and graphite promotes redox reactions that provide electrons to graphite. These electrons raise the Fermi level of graphite and generate the negative zeta potential, consequently, they account for the colloidal stability. [ABSTRACT FROM AUTHOR]

A deep in silico investigation of various microsomal prostaglandin E2 synthase‐1 (mPGES‐1) protein systems is here reported using molecular dynamics (MD) simulations. Firstly, eight different proteins models (Models A−H) were built, starting from the active enzyme trimer system (Model A), namely that bound to three glutathione (GSH) cofactor molecules, and then gradually removing the GSHs (Models B−H), simulating each of them for 100 ns in explicit solvent. The analysis of the obtained data disclosed the structural role of GSH in the chemical architecture of mPGES‐1 enzyme, thus suggesting the unlikely displacement of this cofactor, in accordance with experimentally determined protein structures co‐complexed with small molecule inhibitors. Afterwards, Model A was submitted to microsecond‐scale molecular dynamics simulation (total simulation time=10 μs), in order to shed light about the dynamical behaviour of this enzyme at atomic level and to obtain further structural features and protein function information. We confirmed the structural stability of the enzyme machinery, observing a conformational rigidity of the protein, with a backbone RMSD of ∼3 Å along the simulation time, and highlighting the strong active contribution of GSH molecules due to their active role in packing the protein chains through a tight binding at monomer interfaces. Furthermore, the focused analysis on R73 residue disclosed its role in solvent exchange events, probably excluding its function as route for GSH to enter towards the endoplasmic reticulum membrane, in line with the recently reported function of cap domain residues F44‐D66 as gatekeeper for GSH entrance into catalytic site. [ABSTRACT FROM AUTHOR]

This study was aimed at developing a clinical risk score for cardiovascular autonomic neuropathy (CAN) for type 1 and type 2 diabetes. In a retrospective cross‐sectional one‐centre study in an unselected population, 115 participants with type 1 diabetes (age 41.1 ± 12.2 years) and 161 with type 2 diabetes (age 63.1 ± 8.9 years), well‐characterized for clinical variables, underwent standard cardiovascular reflex tests (CARTs). Strength of associations of confirmed CAN (based on 2 abnormal CARTs) with clinical variables was used to build a CAN risk score. CAN risk score was based on resting heart rate, HbA1c, retinopathy, nephropathy, cardiovascular disease in both type 1 and type 2 diabetes, and on HDL cholesterol, systolic blood pressure, and smoking in type 1 diabetes or insulin treatment and physical activity in type 2 diabetes (range 0‐10). In type 1 diabetes, CAN risk score showed an area under the ROC curve (AUC) of 0.890 ± 0.034, and at cut‐off of 4 sensitivity of 88%, specificity of 74.4%, and negative predictive value (NPV) of 95.7% for confirmed CAN. In type 2 diabetes, CAN risk score showed an AUC of 0.830 ± 0.051 and at the cut‐off of 4 sensitivity and specificity of 78.6% and 73.5%, respectively, and NPV of 97.3% for confirmed CAN. These newly developed CAN risk scores are accessible in clinical practice and, if confirmed in a validation study, they might identify asymptomatic individuals with diabetes at greater risk of CAN to be referred to CARTs, thus limiting the burden of a universal screening. [ABSTRACT FROM AUTHOR]

Short‐fiber‐reinforced‐materials are widely used in industry today. In this paper, microstructure and modal analyses are performed on short‐glass‐fiber‐reinforced polypropylene (PPGF) and short‐natural‐fiber‐reinforced polypropylene (PPNF), to study possible links between the first natural frequency and fibers' orientation and quantify the associated variability. In view of this, different specimens were tested with clamped‐free boundary conditions. The microstructural analysis, performed with micro‐computed tomography studies fibers' properties in injection‐molded plates. This study shows the importance of considering real fibers' orientation for modal predictions. [ABSTRACT FROM AUTHOR]

Stereotactic electroencephalography (SEEG) is an increasingly utilized method for invasive monitoring in patients with medically intractable epilepsy. Yet, the lack of standardization for labeling electrodes hinders communication among clinicians. A rational clustering of contacts based on anatomy rather than arbitrary physical leads may help clinical neurophysiologists interpret seizure networks. We identified SEEG electrodes on post‐implant CTs and registered them to preoperative MRIs segmented according to an anatomical atlas. Individual contacts were automatically assigned to anatomical areas independent of lead. These contacts were then organized using a hierarchical anatomical schema for display and interpretation. Bipolar‐referenced signal cross‐correlations were used to compare the similarity of grouped signals within a conventional montage versus this anatomical montage. As a result, we developed a hierarchical organization for SEEG contacts using well‐accepted, free software that is based solely on their post‐implant anatomical location. When applied to three example SEEG cases for epilepsy, clusters of contacts that were anatomically related collapsed into standardized groups. Qualitatively, seizure events organized using this framework were better visually clustered compared to conventional schemes. Quantitatively, signals grouped by anatomical region were more similar to each other than electrode‐based groups as measured by Pearson correlation. Further, we uploaded visualizations of SEEG reconstructions into the electronic medical record, rendering them durably useful given the interpretable electrode labels. In conclusion, we demonstrate a standardized, anatomically grounded approach to the organization of SEEG neuroimaging and electrophysiology data that may enable improved communication among and across surgical epilepsy teams and promote a clearer view of individual seizure networks. [ABSTRACT FROM AUTHOR]

Strong radar reflections have been previously mapped at the base of the Martian South Polar Layered Deposits. Here, we analyze laboratory measurements of dry and briny samples to determine the cause of this radar return. We find that liquid vein networks consisting of brines at the grain boundaries of ice crystals can greatly enhance the electrical conductivity, thereby causing strong radar reflections. A brine concentration of 2.7–6.0 vol% in ice is sufficient to match the electrical properties of the basal reflection as observed by Mars Advanced Radar for Subsurface and Ionospheric Sounding (MARSIS). When brine is mixed with sediments, the brine‐ice mixture in the pores must be 2–5 times more concentrated in salt, increasing the brine concentration to 6.3–29 vol%. Our best fit of the median observed MARSIS value suggests a salt‐bulk sample concentration of ∼6 wt%. Thus, salt enhancement mechanisms on the order of a magnitude greater than the Phoenix landing site are needed. To form brine, the basal reflector must reach a temperature greater than the eutectic temperature of calcium perchlorate of 197.3 ± 0.2 K, which may be possible if more complex thermal modeling is assumed. Colder metastable brines are possible, but stability over millions of years remains unclear. Conversely, gray hematite with a concentration of 33.2–59.0 vol% possess electrical properties that could cause the observed radar returns, but require concentrations 2–3 times larger than anywhere currently detected. We also argue that brines mixed with high‐surface‐area sediments, or dry red hematite, jarosite, and ilmenite cannot create the observed radar returns at low temperatures. Plain Language Summary: Previous research has detected strong radar reflections from the interface between Mars' southern ice cap and their underlying sediments over a region with an area of 20 × 30 km and 1.5 kms beneath the surface. Radar reflections are caused by changes in electrical properties. Here, we analyze electrical property laboratory measurements of materials under Mars‐like conditions. We find that a small amount of brine in ice samples could create strong radar reflections similar to those that are observed. A greater concentration of salt is needed in sediment‐ice mixtures. We suspect that the sublimation of a previous version of the ice cap may have deposited salt via sublimation in the base of the current ice cap. Additionally, the temperature at the base of the ice cap must be warmer than simple thermal models estimate, we suggest insulating materials such as CO2 ice may be incorporated into the ice cap. Additionally, dry gray hematite could also cause the observed radar returns, but must be even more concentrated than anywhere yet discovered on Mars. We can also rule out any brines mixed with clays, or dry red hematite, jarosite, and ilmenite as they cannot create the observed radar returns at low temperature. Key Points: Brines possess a significantly higher real part of dielectric permittivity and Direct Current (DC) conductivity than dry and frozen mineralsSalt enhancements of 5–16 times the salt‐regolith concentration at the Phoenix landing site is needed in brine‐sediment mixturesThe basal unit must be equal or greater than the eutectic temperature of calcium perchlorate (197.3 ± 0.2 K) to allow for brine formation [ABSTRACT FROM AUTHOR]

Background: The incidence of multidrug resistant organisms (MDROs) infections among solid organ transplant (SOT) patients is very high in Brazil. Methods: This review will discuss antimicrobial use and resistance in SOT in Brazil, highlighting the main barriers and facilitators for implementation of an antimicrobial stewardship programme (ASP). Results: The most common group of MDROs is carbapenem‐resistant Gram‐negative bacteria and vancomycin‐resistant Enterococcus. Carbapenem‐resistant Enterobacterales (CREs) are the most frequent MDROs and have been reported as donor‐derived as well. Although ASPs are mandatory in the country, there is a lack of information regarding ASPs in SOT recipients. The main barriers for the implementation of ASPs in Brazilian hospitals are lack of electronic medical records, absence of national guidelines specific to SOT recipients, lack of recommendations on surveillance culture to evaluate colonization and transmission of donor‐derived MDROs, limited availability of rapid diagnostic tests, and insufficient pharmacist and clinician time allocated to ASP activities in some SOT centers. Conclusions: The incidence of MDRO infections caused mainly by VREs and CREs is very high in the country. There is limited data regarding antimicrobial use among SOT recipients in Brazil. The absence of antimicrobial stewardship national guidelines specific to SOT recipients is one of the main barriers for the implementation of ASPs in Brazilian hospitals. [ABSTRACT FROM AUTHOR]

6‐methylquinazolin‐4(3H)‐one‐based compounds were here identified and synthesized as novel binders of bromodomain‐containing protein 9 (BRD9) epigenetic reader. Accounting a fast and efficient synthetic route aimed to easily obtain differently 2‐ and 8‐disubstituted 6‐methylquinazolin‐4(3H)‐one derivatives, a virtual library of synthesizable items was built and submitted to molecular docking experiments. Based on two 3D structure‐based pharmacophore models recently developed by us on BRD9, 16 compounds were selected and synthesized, using mild conditions with good yields in relatively short reaction times. Among them, 14, 16, 18, 22, and 26 emerged as the most potent compounds of these series, able to bind BRD9 at the low micromolar range of concentrations. These molecules also showed a promising selective behavior when tested against BRD4 bromodomain. These results highlighted the quinazolin‐4(3H)‐one chemical core as a valuable scaffold for developing promising BRD9 binders. [ABSTRACT FROM AUTHOR]

Multi‐electrode arrays with 3D micropillars allow the recording of electrophysiological signals in vitro with higher precision and signal‐to‐noise ratio than planar arrays. This is the result of the tight interaction between the 3D electrode and the cell membrane. Most 3D electrodes are manufactured on rigid substrates and their integration on flexible substrates is largely unexplored. Here, a straightforward approach is presented for fabricating soft interfaces featuring 3D poly(3,4‐ethylenedioxythiophene)‐poly(styrenesulfonate) (PEDOT:PSS) micropillars on a soft flexible substrate made of polydimethylsiloxane (PDMS). Large‐area isotropic arrays of PEDOT:PSS micropillars with tailored geometric area, surface properties, and electrochemical characteristics are fabricated via a combination of soft‐lithography and electrodeposition. A 60% increase in capacitance is achieved for high density micropillars compared to planar electrodes and this is found to be correlated with the increased electroactive surface area. Furthermore, 3D PEDOT:PSS micropillars support adhesion, growth and differentiation of SH‐SY5Y cells, and influence the direction of neurite outgrowth. Finally, by virtue of their elasticity, soft micropillars act as excellent anchoring loci for elongating neurites, facilitating their bending and twisting around the micropillar, increasing the number of contact points between the cells and the electrode, a key requirement to obtain high performance neural interfaces. [ABSTRACT FROM AUTHOR]

Background: Peripheral blood stem cells (PBSCs) are the predominant graft source for adult allogeneic hematopoietic stem cell transplantation (HSCT). In poorly mobilized autologous donors, plerixafor improves collection outcomes. We examine plerixafor use in allogeneic donors who mobilize poorly with granulocyte colony‐stimulating factor (G‐CSF) in those who are healthy and those with pre‐existing medical conditions, and determine the optimal threshold to add plerixafor. Study Design/Methods: We retrospectively examined all allogeneic PBSC collections from January 2013 to October 2020 at our center. Donors received G‐CSF 10 mcg/kg daily for 4 days before undergoing apheresis collection on day 5. Plerixafor was added based on poor CD34+ cell collection yield after the first or second collection day. Results: Of the 1008 allogeneic donors, 41 (4.1%) received one dose of plerixafor in addition to G‐CSF due to poor collection yield. After starting plerixafor there was a 0.75‐ to 7.74‐fold (median 2.94) increase in CD34+ yield from the previous day. No donors with G‐CSF‐only mobilization who collected <2.0 × 106 CD34+ cells/kg recipient weight on day one achieved the goal of ≥4.0 × 106 CD34+ cells/kg recipient weight total over 2 days but 59.2% of donors who used rescue plerixafor did. Conclusion: Donors both healthy and those with pre‐existing disease responded well to plerixafor with minimal side effects. If the first‐day collection yield is less than ~63% of the collection goal, addition of plerixafor may be necessary to reach the collection goal and limit the number of collection days in allogeneic donors. [ABSTRACT FROM AUTHOR]

Background: Serological tests are a powerful tool in the monitoring of infectious diseases and the detection of host immunity. However, manufacturers often provide diagnostic accuracy data generated through biased studies, and the performance in clinical practice is essentially unclear. Objectives: We aimed to determine the diagnostic accuracy of various serological testing strategies for (a) identification of patients with previous coronavirus disease‐2019 (COVID‐19) and (b) prediction of neutralizing antibodies against SARS‐CoV‐2 in real‐life clinical settings. Methods: We prospectively included 2573 consecutive health‐care workers and 1085 inpatients with suspected or possible previous COVID‐19 at a Swiss University Hospital. Various serological immunoassays based on different analytical techniques (enzyme‐linked immunosorbent assays, ELISA; chemiluminescence immunoassay, CLIA; electrochemiluminescence immunoassay, ECLIA; and lateral flow immunoassay, LFI), epitopes of SARS‐CoV‐2 (nucleocapsid, N; receptor‐binding domain, RBD; extended RBD, RBD+; S1 or S2 domain of the spike [S] protein, S1/S2), and antibody subtypes (IgG, pan‐Ig) were conducted. A positive real‐time PCR test from a nasopharyngeal swab was defined as previous COVID‐19. Neutralization assays with live SARS‐CoV‐2 were performed in a subgroup of patients to assess neutralization activity (n = 201). Results: The sensitivity to detect patients with previous COVID‐19 was ≥85% in anti‐N ECLIA (86.8%) and anti‐S1 ELISA (86.2%). Sensitivity was 84.7% in anti‐S1/S2 CLIA, 84.0% in anti‐RBD+LFI, 81.0% in anti‐N CLIA, 79.2% in anti‐RBD ELISA, and 65.6% in anti‐N ELISA. The specificity was 98.4% in anti‐N ECLIA, 98.3% in anti‐N CLIA, 98.2% in anti‐S1 ELISA, 97.7% in anti‐N ELISA, 97.6% in anti‐S1/S2 CLIA, 97.2% in anti‐RBD ELISA, and 96.1% in anti‐RBD+LFI. The sensitivity to detect neutralizing antibodies was ≥85% in anti‐S1 ELISA (92.7%), anti‐N ECLIA (91.7%), anti‐S1/S2 CLIA (90.3%), anti‐RBD+LFI (87.9%), and anti‐RBD ELISA (85.8%). Sensitivity was 84.1% in anti‐N CLIA and 66.2% in anti‐N ELISA. The specificity was ≥97% in anti‐N CLIA (100%), anti‐S1/S2 CLIA (97.7%), and anti‐RBD+LFI (97.9%). Specificity was 95.9% in anti‐RBD ELISA, 93.0% in anti‐N ECLIA, 92% in anti‐S1 ELISA, and 65.3% in anti‐N ELISA. Diagnostic accuracy measures were consistent among subgroups. Conclusions: The diagnostic accuracy of serological tests for SARS‐CoV‐2 antibodies varied remarkably in clinical practice, and the sensitivity to identify patients with previous COVID‐19 deviated substantially from the manufacturer's specifications. The data presented here should be considered when using such tests to estimate the infection burden within a specific population and determine the likelihood of protection against re‐infection. [ABSTRACT FROM AUTHOR]