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The objective of this investigation was to improve the diagnosis of breast cancer by combining two significant datasets: the Wisconsin Breast Cancer Database and the DDSM Curated Breast Imaging Subset (CBIS-DDSM). The Wisconsin Breast Cancer Database provides a detailed examination of the characteristics of cell nuclei, including radius, texture, and concavity, for 569 patients, of which 212 had malignant tumors. In addition, the CBIS-DDSM dataset-a revised variant of the Digital Database for Screening Mammography (DDSM)-offers a standardized collection of 2,620 scanned film mammography studies, including cases that are normal, benign, or malignant and that include verified pathology data. To identify complex patterns and trait diagnoses of breast cancer, this investigation used a hybrid deep learning methodology that combines Convolutional Neural Networks (CNNs) with the stochastic gradients method. The Wisconsin Breast Cancer Database is used for CNN training, while the CBIS-DDSM dataset is used for fine-tuning to maximize adaptability across a variety of mammography investigations. Data integration, feature extraction, model development, and thorough performance evaluation are the main objectives. The diagnostic effectiveness of the algorithm was evaluated by the area under the Receiver Operating Characteristic Curve (AUC-ROC), sensitivity, specificity, and accuracy. The generalizability of the model will be validated by independent validation on additional datasets. This research provides an accurate, comprehensible, and therapeutically applicable breast cancer detection method that will advance the field. These predicted results might greatly increase early diagnosis, which could promote improvements in breast cancer research and eventually lead to improved patient outcomes., (© 2024. The Author(s).)

Mapping the production of Ecosystem Services (ES) is imperative for sustainable ecosystem management. Likewise, incorporating expert knowledge enhances ES research. Here, we calculate eight multi-temporal ES indicators for mainland Portugal using a spatial modelling approach. These indicators are then integrated into the novel ASEBIO index-Assessment of Ecosystem Services and Biodiversity-which depicts a combined ES potential based on CORINE Land Cover, using a multi-criteria evaluation method with weights defined by stakeholders through an Analytical Hierarchy Process (AHP). Outputs from the modelling show how ES have changed in Portugal in relation to land use changes, including trade-offs between 1990 and 2018. The composed ASEBIO index is compared against the stakeholders' valuation of ES potential for the year 2018. The results reveal a significant mismatch between the ES potential perceived by stakeholders and the models, with stakeholder estimates being 32.8% higher on average. All the selected ES were overestimated by the stakeholders. Drought regulation and erosion prevention have the highest contrasts, while water purification, food production and recreation are the most closely aligned among both approaches. Providing the first national overview about the status of multiple ES over a 28 year-period, our findings highlight potential disparities between data-driven and stakeholder-based evaluations. Therefore, we suggest the need for integrative strategies that consider scientific models with expert knowledge for more effective ES assessments and land-use planning. This approach could help bridge the gap between data-driven models and human perspectives, resulting in more balanced and inclusive decision-making., (© 2024. The Author(s).)

Life sciences research and experimentation are resource-intensive, requiring extensive trials and considerable time. Often, experiments do not achieve their intended objectives, but progress is made through trial and error, eventually leading to breakthroughs. Machine learning is transforming this traditional approach, providing methods to expedite processes and accelerate discoveries. Deep Learning is becoming increasingly prominent in chemistry, with Convolutional Graph Networks (CGN) being a key focus, though other approaches also show significant potential. This research explores the application of Natural Language Processing (NLP) to evaluate the effectiveness of chemical language representations, specifically SMILES and SELFIES, using tokenization methods such as Byte Pair Encoding (BPE) and a novel approach developed in this study, Atom Pair Encoding (APE), in BERT-based models. The primary objective is to assess how these tokenization techniques influence the performance of chemical language models in biophysics and physiology classification tasks. The findings reveal that APE, particularly when used with SMILES representations, significantly outperforms BPE by preserving the integrity and contextual relationships among chemical elements, thereby enhancing classification accuracy. Performance was evaluated in downstream classification tasks using three distinct datasets for HIV, toxicology, and blood-brain barrier penetration, with ROC-AUC serving as the evaluation metric. This study highlights the critical role of tokenization in processing chemical language and suggests that refining these techniques could lead to significant advancements in drug discovery and material science., (© 2024. The Author(s).)

Modern natural language processing (NLP) state-of-the-art (SoTA) deep learning (DL) models have hundreds of millions of parameters, making them extremely complex. Large datasets are required for training these models, and while pretraining has reduced this requirement, human-labelled datasets are still necessary for fine-tuning. Few-shot learning (FSL) techniques, such as meta-learning, try to train models from smaller datasets to mitigate this cost. However, the tasks used to evaluate these meta-learners frequently diverge from the problems in the real world that they are meant to resolve. This work aims to apply meta-learning to a problem that is more pertinent to the real world: class incremental learning (IL). In this scenario, after completing its training, the model learns to classify newly introduced classes. One unique quality of meta-learners is that they can generalise from a small sample size to classes that have never been seen before, which makes them especially useful for class incremental learning (IL). The method describes how to emulate class IL using proxy new classes. This method allows a meta-learner to complete the task without the need for retraining. To generate predictions, the transformer-based aggregation function in a meta-learner that modifies data from examples across all classes has been proposed. The principal contributions of the model include concurrently considering the entire support and query sets, and prioritising attention to crucial samples, such as the question, to increase the significance of its impact during inference. The outcomes demonstrate that the model surpasses prevailing benchmarks in the industry. Notably, most meta-learners demonstrate significant generalisation in the context of class IL even without specific training for this task. This paper establishes a high-performing baseline for subsequent transformer-based aggregation techniques, thereby emphasising the practical significance of meta-learners in class IL., (© 2024. The Author(s).)

In this paper, we present the potential of Terahertz Time-Domain Imaging (THz-TDI) as a tool to perform non-invasive 3D analysis of an ancient enamel plate manufactured by Longwy Company in France. The THz data collected in the reflection mode were processed using noise filtering procedures and an advanced imaging approach. The results validate the capability to identify glaze layers and the thickness of ceramic materials. To characterize the nature of the pigments, we also use with X-ray images, visible near-infrared hyperspectral imaging spectroscopy, and p-XRF (portable X-ray fluorescence) to qualitatively and quantitively identify the materials used. The obtained information enables a better understanding of the decoration chromogens nature and, thus, to determine the color palette of the artists who produced such decorative object. We also establish the efficiency of a focus, Z-tracker, which enables to perform THz imaging on non-flat samples and to attenuate artifacts obtained with a short focus lens. Then, 3D images are extracted and generated, providing a real vision. We also report the evaluation of the internal damage state through the detection of fractures., (© 2024. The Author(s).)

Excess amounts of histones in the cell induce mitotic chromosome loss and genomic instability, and are therefore detrimental to cell survival. In yeast, excess histones are degraded by the proteasome mediated via the DNA damage response factor Rad53. Histone expression, therefore, is tightly regulated at the protein level. Our understanding of the transcriptional regulation of histone genes is far from complete. In this study, we found that calcineurin inhibitor treatment increased histone protein levels, and that the transcription factor NFATc1 (nuclear factor of activated T cells 1) repressed histone transcription and acts downstream of the calcineurin. We further revealed that NFATc1 binds to the promoter regions of many histone genes and that histone transcription is downregulated in a manner dependent on intracellular calcium levels. Indeed, overexpression of histone H3 markedly inhibited cell proliferation. Taken together, these findings suggest that NFATc1 prevents the detrimental effects of histone H3 accumulation by inhibiting expression of histone at the transcriptional level., (© 2024. The Author(s).)

Familial platelet disorder with associated myeloid malignancies (FPDMM) is an autosomal dominant disease caused by heterozygous germline mutations in RUNX1. It is characterized by thrombocytopenia, platelet dysfunction, and a predisposition to hematological malignancies. Although FPDMM is a precursor for diseases involving abnormal DNA methylation, the DNA methylation status in FPDMM remains unknown, largely due to a lack of animal models and challenges in obtaining patient-derived samples. Here, using genome editing techniques, we established two lines of human induced pluripotent stem cells (iPSCs) with different FPDMM-mimicking heterozygous RUNX1 mutations. These iPSCs showed defective differentiation of hematopoietic progenitor cells (HPCs) and megakaryocytes (Mks), consistent with FPDMM. The FPDMM-mimicking HPCs showed DNA methylation patterns distinct from those of wild-type HPCs, with hypermethylated regions showing the enrichment of ETS transcription factor (TF) motifs. We found that the expression of FLI1, an ETS family member, was significantly downregulated in FPDMM-mimicking HPCs with a RUNX1 transactivation domain (TAD) mutation. We demonstrated that FLI1 promoted binding-site-directed DNA demethylation, and that overexpression of FLI1 restored their megakaryocytic differentiation efficiency and hypermethylation status. These findings suggest that FLI1 plays a crucial role in regulating DNA methylation and correcting defective megakaryocytic differentiation in FPDMM-mimicking HPCs with a RUNX1 TAD mutation., (© 2024. The Author(s).)

In this study, a commercial dental resin was reinforced by SiO 2 nanoparticles (NPs) with different concentrations to enhance its mechanical functionality. The material characterization and finite element analysis (FEA) have been performed to evaluate the mechanical properties. Wedge indentation and 3-point bending tests were conducted to assess the mechanical behavior of the prepared nanocomposites. The results revealed that the optimal content of NPs was achieved at 1% SiO 2 , resulting in a 35% increase in the indentation reaction force. Therefore, the sample containing 1% SiO 2 NPs was considered for further tests. The morphology of selected sample was examined using field emission scanning electron microscopy (FE-SEM), revealing the homogeneous dispersion of SiO 2 NPs with minimal agglomeration. X-ray diffraction (XRD) was employed to investigate the crystalline structure of the selected sample, indicating no change in the dental resin state upon adding SiO 2 NPs. In the second part of the study, a novel approach called iterative FEA, supported by the experiment wedge indentation test, was used to determine the mechanical properties of the 1% SiO 2 -dental resin. Subsequently, the accurately determined material properties were assigned to a dental crown model to virtually investigate its behavior under oblique loading. The virtual test results demonstrated that most microcracks initiated from the top of the crown and extended through its thickness., (© 2024. The Author(s).)

The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients., (© 2024. The Author(s).)

Atopic dermatitis (AD) is a common inflammatory skin condition that significantly affects patients' lives and imposes both economic and non-economic burdens. The precise societal and individual consequences of AD remain incompletely understood. This study aimed to characterize AD in Portuguese patients and assess its personal, familial, and societal implications, including health status and quality of life. The research, conducted from June 2019 to January 2020, involved 204 confirmed AD patients in Portugal, who completed a 70-question questionnaire. Results show that, on average, patients experienced a two-year delay in diagnosis, with two-thirds having allergic comorbidities. Late-onset AD (after age 20) was found to be correlated with worsening symptoms post-diagnosis. Globally, patients reported substantial effects on health, quality of life, and mental well-being. Effects include significant levels of anxiety, frustration and sleep disorders. Severe AD correlated with more suffering and reduced perceived health, indicating a link between disease severity and quality of life. Remarkably, despite questionable effectiveness, 92% of severe AD patients were prescribed antihistamines, while only 19% received biological treatments. In Portugal, delayed AD diagnosis hinders timely treatment, and despite its profound impact and high comorbidity rates, AD patients tend to remain undertreated. Recognizing the personal and societal repercussions is crucial for enhancing care, contributing to improving QoL, social functioning and global well-being., (© 2024. The Author(s).)

The pronounced change in the profile of hospitalized patients during COVID-19 and the severe respiratory component of this disease, with a great need for mechanical ventilation, led to changes in the consumption pattern of some medicines and supplies. This time-series study analyzed the in-hospital consumption of opioids during the COVID-19 pandemic in 24 Brazilian hospitals compared to the pre-pandemic period. Data included 711,883 adult patients who had opioids prescribed. In 2020, the mean consumption was significantly higher compared to 2019 for parenteral fentanyl, enteral methadone, and parenteral methadone. It was significantly lower for parenteral morphine parenteral sufentanil, and parenteral tramadol. For remifentanil, it did not differ. The number of patients in 2020 was lower but the mean consumption was higher for fentanyl, parenteral methadone, and remifentanil. It was lower for enteral methadone and parenteral sufentanil. The consumption of parenteral morphine and parenteral tramadol was stable. There was a relevant increase in hospital consumption of some potent opioids during the COVID-19 pandemic in Brazil. These results reinforce the concern about epidemiological surveillance of opioid use after periods of increased hospital use since in-hospital consumption can be the gateway to the misuse or other than the prescribed use of opioids after discharge., (© 2023. Springer Nature Limited.)

Piezoelectric nanogenerators (PENGs) have attracted great interest owing to their broad range application in environmental mechanical energy harvesting to power small electronic devices. In this study, novel flexible and high-performance double-layer sandwich-type PENGs based on one-dimensional (1-D) and two-dimensional (2-D) zinc oxide (ZnO) nanostructures and Ni foam as the middle layer have been developed. The morphology and structure of 1- and 2-D ZnO nanostructures have been studied by scanning electron microscopy (SEM) and X-ray diffraction (XRD). To investigate the effect of structural design on the piezoelectric performance, single-layer PENGs were also fabricated. The piezoelectric output of all prepared PENGs were evaluated under different human impacts at various forces and frequencies. The double-layer designed PENGs showed a two times larger voltage output compared to the single-layer PENGs, and the use of Ni foam as middle-layer and of 2-D ZnO nanosheets (compared to 1-D nanorods) was also found to increase the performance of the designed PENGs. The working mechanism of the prepared PENGs is also discussed. The design of nanogenerators as double-layer sandwich structures instead of two integrated single-layer devices reduces the overall preparation time and processing steps and enhances their output performance, thus opening the gate for widening their practical applications., (© 2023. Springer Nature Limited.)

Multiple Sclerosis (MS) is an autoimmune demyelinating disease characterised by changes in iron and myelin content. These biomarkers are detectable by Quantitative Susceptibility Mapping (QSM), an advanced Magnetic Resonance Imaging technique detecting magnetic properties. When analysed with radiomic techniques that exploit its intrinsic quantitative nature, QSM may furnish biomarkers to facilitate early diagnosis of MS and timely assessment of progression. In this work, we explore the robustness of QSM radiomic features by varying the number of grey levels (GLs) and echo times (TEs), in a sample of healthy controls and patients with MS. We analysed the white matter in total and within six clinically relevant tracts, including the cortico-spinal tract and the optic radiation. After optimising the number of GLs (n = 64), at least 65% of features were robust for each Volume of Interest (VOI), with no difference (p > .05) between left and right hemispheres. Different outcomes in feature robustness among the VOIs depend on their characteristics, such as volume and variance of susceptibility values. This study validated the processing pipeline for robustness analysis and established the reliability of QSM-based radiomics features against GLs and TEs. Our results provide important insights for future radiomics studies using QSM in clinical applications., (© 2023. Springer Nature Limited.)

Organized retail crime (ORC) is a significant issue for retailers, marketplace platforms, and consumers. Its prevalence and influence have increased fast in lockstep with the expansion of online commerce, digital devices, and communication platforms. Today, it is a costly affair, wreaking havoc on enterprises' overall revenues and continually jeopardizing community security. These negative consequences are set to rocket to unprecedented heights as more people and devices connect to the Internet. Detecting and responding to these terrible acts as early as possible is critical for protecting consumers and businesses while also keeping an eye on rising patterns and fraud. The issue of detecting fraud in general has been studied widely, especially in financial services, but studies focusing on organized retail crimes are extremely rare in literature. To contribute to the knowledge base in this area, we present a scalable machine learning strategy for detecting and isolating ORC listings on a prominent marketplace platform by merchants committing organized retail crimes or fraud. We employ a supervised learning approach to classify postings as fraudulent or real based on past data from buyer and seller behaviors and transactions on the platform. The proposed framework combines bespoke data preprocessing procedures, feature selection methods, and state-of-the-art class asymmetry resolution techniques to search for aligned classification algorithms capable of discriminating between fraudulent and legitimate listings in this context. Our best detection model obtains a recall score of 0.97 on the holdout set and 0.94 on the out-of-sample testing data set. We achieve these results based on a select set of 45 features out of 58., (© 2023. The Author(s).)

Commensal bacteria-derived metabolites are critical in regulating the host immune system. Although the impact of gut microbiota-derived hydrophilic metabolites, such as short-chain fatty acids, on immune cell functions and development has been well documented, the immunomodulatory effects of gut microbiota-derived lipids are still of interest. Here, we report that lipid extracts from the feces of specific-pathogen-free (SPF), but not germ-free (GF), mice showed regulatory T (Treg)-cell-inducing activity. We conducted RP-HPLC-based fractionation and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipidome profiling and identified two bioactive lipids, 9,10-dihydroxy-12Z-octadecenoic acid (9,10-DiHOME) and all-trans retinoic acid (atRA), with Treg-inducing activity in vitro. The luminal abundance of 9,10-DiHOME in the large intestine was significantly decreased by dextran sulfate sodium (DSS)-induced colitis, indicating that 9,10-DiHOME may be a potential biomarker of colitis. These observations implied that commensal bacteria-derived lipophilic metabolites might contribute to Treg development in the large intestine., (© 2023. The Author(s).)

The potential health risks of exposure to radiofrequency electromagnetic fields from mobile communications technologies have raised societal concerns. Guidelines have been set to protect the population (e.g. non-specific heating above 1 °C under exposure to radiofrequency fields), but questions remain regarding the potential biological effects of non-thermal exposures. With the advent of the fifth generation (5G) of mobile communication, assessing whether exposure to this new signal induces a cellular stress response is one of the mandatory steps on the roadmap for a safe deployment and health risk evaluation. Using the BRET (Bioluminescence Resonance Energy-Transfer) technique, we assessed whether continuous or intermittent (5 min ON/ 10 min OFF) exposure of live human keratinocytes and fibroblasts cells to 5G 3.5 GHz signals at specific absorption rate (SAR) up to 4 W/kg for 24 h impact basal or chemically-induced activity of Heat Shock Factor (HSF), RAt Sarcoma virus (RAS) and Extracellular signal-Regulated Kinases (ERK) kinases, and Promyelocytic Leukemia Protein (PML), that are all molecular pathways involved in environmental cell-stress responses. The main results are (i), a decrease of the HSF1 basal BRET signal when fibroblasts cells were exposed at the lower SARs tested (0.25 and 1 W/kg), but not at the highest one (4 W/kg), and (ii) a slight decrease of As 2 O 3 maximal efficacy to trigger PML SUMOylation when fibroblasts cells, but not keratinocytes, were continuously exposed to the 5G RF-EMF signal. Nevertheless, given the inconsistency of these effects in terms of impacted cell type, effective SAR, exposure mode, and molecular cell stress response, we concluded that our study show no conclusive evidence that molecular effects can arise when skin cells are exposed to the 5G RF-EMF alone or with a chemical stressor., (© 2023. The Author(s).)

The extraordinary circumstances of the COVID-19 pandemic led to measures to mitigate the spread of the disease, with lockdowns and mobility restrictions at national and international levels. These measures led to sudden and sometimes dramatic reductions in human activity, including significant reductions in ship traffic in the maritime sector. We report on a reduction of deep-ocean acoustic noise in three ocean basins in 2020, based on data acquired by hydroacoustic stations in the International Monitoring System of the Comprehensive Nuclear-Test-Ban Treaty. The noise levels measured in 2020 are compared with predicted levels obtained from modelling data from previous years using Gaussian Process regression. Comparison of the predictions with measured data for 2020 shows reductions of between 1 and 3 dB in the frequency range from 10 to 100 Hz for all but one of the stations., (© 2023. The Author(s).)

Glycans play an important role in biology with multiple cellular functions ranging from cell signaling, mobility and growth to protein folding and localization. The N-glycosylation state within a tissue has been found to vary greatly between healthy and diseased patients and has proven to have an important clinical diagnostic value. Matrix assisted laser-desorption ionization (MALDI) mass spectrometry imaging (MSI) allows for untargeted analysis of biomolecules, including N-glycans, on a tissue section and provides a spatial context of the analyte. Until now, N-glycans have been predominantly analyzed using MALDI MSI on formalin-fixed paraffin embedded (FFPE) tissue sections, however this greatly reduces the clinical applicability, as the FFPE embedding process alters the biological environment of the tissue. Here we developed a protocol that allows for MALDI MSI of N-glycans from fresh frozen tissue that matches the current standard of FFPE analysis. By optimizing several steps in the sample preparation, we see orders of magnitude increase in signal intensity. Furthermore, this method limits delocalization of released N-glycans, thus improving the effective spatial resolution of the label-free molecular images. This protocol provides a novel perspective towards clinical application of MALDI MSI and capitalizes on the diagnostic value of N-glycan analysis., (© 2023. The Author(s).)

Crocodilians are a taxonomic group of large predators with important ecological and evolutionary benefits for ecosystem functioning in the face of global change. Anthropogenic actions affect negatively crocodilians' survival and more than half of the species are threatened with extinction worldwide. Here, we map and explore three dimensions of crocodilian diversity on a global scale. To highlight the ecological importance of crocodilians, we correlate the spatial distribution of species with the ecosystem services of nutrient retention in the world. We calculate the effectiveness of global protected networks in safeguarding crocodilian species and provide three prioritization models for conservation planning. Our results show the main hotspots of ecological and evolutionary values are in southern North, Central and South America, west-central Africa, northeastern India, and southeastern Asia. African species have the highest correlation to nutrient retention patterns. Twenty-five percent of the world's crocodilian species are not significantly represented in the existing protected area networks. The most alarming cases are reported in northeastern India, eastern China, and west-central Africa, which include threatened species with low or non-significant representation in the protected area networks. Our highest conservation prioritization model targets southern North America, east-central Central America, northern South America, west-central Africa, northeastern India, eastern China, southern Laos, Cambodia, and some points in southeastern Asia. Our research provides a global prioritization scheme to protect multiple dimensions of crocodilian diversity for achieving effective conservation outcomes., (© 2023. The Author(s).)

Exposure to heavy metals can affect cell differentiation, neurocognitive development, and growth during early life, even in low doses. Little is known about heavy metal exposure and its relationship with nutrition outcomes in non-mining rural environments. We carried out a community-based cross-sectional study to describe the distribution of four heavy metal concentrations [arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg)] in the serum of a representative population of children aged 12 to 59 months old from the rural region of Popokabaka, Democratic Republic of Congo. The four metals were measured in 412 samples using inductively coupled plasma-mass spectrometry (ICP-MS). Limits of detection (LoD) and quantification (LoQ) were set. Percentiles were reported. Statistical and geospatial bivariate analyses were performed to identify relationships with other nutrition outcomes. Arsenic was quantified in 59.7%, while Cd, Hg, and Pb were quantified in less than 10%, all without toxicities. The arsenic level was negatively associated with the zinc level, while the Hg level was positively associated with the selenium level. This common detection of As in children of Popokabaka requires attention, and urgent drinking water exploration and intervention for the profit of the Popokabaka community should be considered., (© 2022. The Author(s).)

Polyp detection through colonoscopy is a widely used method to prevent colorectal cancer. The automation of this process aided by artificial intelligence allows faster and improved detection of polyps that can be missed during a standard colonoscopy. In this work, we propose to implement various object detection algorithms for polyp detection. To improve the mean average precision (mAP) of the detection, we combine the baseline models through a stacking approach. The experiments demonstrate the potential of this new methodology, which can reduce the workload for oncologists and increase the precision of the localization of polyps. Our proposal achieves a mAP of 0.86, translated into an improvement of 34.9% compared to the best baseline model and 28.8% with respect to the weighted boxes fusion ensemble technique., (© 2022. The Author(s).)

In breast cancer, Poly(ADP-ribose) polymerase 3 (PARP3) has been identified as a key driver of tumor aggressiveness exemplifying its selective inhibition as a promising surrogate for clinical activity onto difficult-to-treat cancers. Here we explored the role of PARP3 in the oncogenicity of glioblastoma, the most aggressive type of brain cancer. The absence of PARP3 did not alter cell proliferation nor the in vivo tumorigenic potential of glioblastoma cells. We identified a physical and functional interaction of PARP3 with the histone H3 lysine 9 methyltransferase G9a. We show that PARP3 helps to adjust G9a-dependent repression of the adhesion genes Nfasc and Parvb and the hypoxia-responsive genes Hif-2α, Runx3, Mlh1, Ndrg1, Ndrg2 and Ndrg4. Specifically for Nfasc, Parvb and Ndrg4, PARP3/G9a cooperate for an adjusted establishment of the repressive mark H3K9me2. While examining the functional consequence in cell response to hypoxia, we discovered that PARP3 acts to maintain the cytoskeletal microtubule stability. As a result, the absence of PARP3 markedly increases the sensitivity of glioblastoma cells to microtubule-destabilizing agents providing a new therapeutic avenue for PARP3 inhibition in brain cancer therapy., (© 2022. The Author(s).)

In the process of terahertz (THz) wave generation via optical rectification of infrared femtosecond pulses in a non-linear optical crystal, the power of terahertz wave is directly proportional to the square of the optical pump power. Therefore, high power terahertz wave can be generated using a high power femtosecond laser provided that the crystal has both high laser induced damage threshold and optical non-linear coefficient. However, a significant amount of pump power is lost in this process due to the Fresnel's reflection at the air-crystal boundary. In this paper, we numerically and experimentally demonstrate that the coat of optical thin film called Cytop on the 4-N, N-dimethylamino-4'-N'-methyl-stilbazolium tosylate (DAST) crystal effectively reduces the reflection loss of pump power, thereby increasing the THz wave emission efficiency of the DAST crystal. We found that the average power of THz wave emitted by the thin film coated crystal is about 28% higher than the THz power emitted by the uncoated crystal when an equal amount of laser power is used. The thin film coated DAST crystals can be used not only in terahertz measurement systems but also in optical devices such as modulators and waveguides., (© 2022. The Author(s).)

Hidradenitis suppurativa (HS) is a recurrent inflammatory skin disease with a complex etiopathogenesis whose treatment poses a challenge in the clinical practice. Here, we present a novel integrated pipeline produced by the European consortium BATMAN (Biomolecular Analysis for Tailored Medicine in Acne iNversa) aimed at investigating the molecular pathways involved in HS by developing new diagnosis algorithms and building cellular models to pave the way for personalized treatments. The objectives of our european Consortium are the following: (1) identify genetic variants and alterations in biological pathways associated with HS susceptibility, severity and response to treatment; (2) design in vitro two-dimensional epithelial cell and tri-dimensional skin models to unravel the HS molecular mechanisms; and (3) produce holistic health records HHR to complement medical observations by developing a smartphone application to monitor patients remotely. Dermatologists, geneticists, immunologists, molecular cell biologists, and computer science experts constitute the BATMAN consortium. Using a highly integrated approach, the BATMAN international team will identify novel biomarkers for HS diagnosis and generate new biological and technological tools to be used by the clinical community to assess HS severity, choose the most suitable therapy and follow the outcome., (© 2022. The Author(s).)

Chemically functionalized or coated sensors are by far the most employed solution in gas sensing. However, their poor long term stability represents a concern in applications dealing with hazardous gases. Uncoated sensors are durable but their selectivity is poor or non-existent. In this study, multi-parametric discrimination is used as an alternative to selectivity for uncoated capacitive micromachined ultrasonic transducers (CMUTs). This paper shows how measuring simultaneously the attenuation coefficient and the time of flight under different nitrogen mixtures allows to identify hydrogen, carbon dioxide and methane from each other and determine their concentration along with identification of temperature and humidity drifts. Theoretical comparison and specific signal processing to deal with the issue of multiple reflections are also presented. Some potential applications are monitoring of refueling stations, vehicles and nuclear waste storage facilities., (© 2022. The Author(s).)

Anhydrobiosis, one of the most extensively studied forms of cryptobiosis, is induced in certain organisms as a response to desiccation. Anhydrobiotic species has been hypothesized to produce substances that can protect their biological components and/or cell membranes without water. In extremotolerant tardigrades, highly hydrophilic and heat-soluble protein families, cytosolic abundant heat-soluble (CAHS) proteins, have been identified, which are postulated to be integral parts of the tardigrades' response to desiccation. In this study, to elucidate these protein functions, we performed in vitro and in vivo characterizations of the reversible self-assembling property of CAHS1 protein, a major isoform of CAHS proteins from Ramazzottius varieornatus, using a series of spectroscopic and microscopic techniques. We found that CAHS1 proteins homo-oligomerized via the C-terminal α-helical region and formed a hydrogel as their concentration increased. We also demonstrated that the overexpressed CAHS1 proteins formed condensates under desiccation-mimicking conditions. These data strongly suggested that, upon drying, the CAHS1 proteins form oligomers and eventually underwent sol-gel transition in tardigrade cytosols. Thus, it is proposed that the CAHS1 proteins form the cytosolic fibrous condensates, which presumably have variable mechanisms for the desiccation tolerance of tardigrades. These findings provide insights into molecular strategies of organisms to adapt to extreme environments., (© 2021. The Author(s).)

Robust machine learning models based on radiomic features might allow for accurate diagnosis, prognosis, and medical decision-making. Unfortunately, the lack of standardized radiomic feature extraction has hampered their clinical use. Since the radiomic features tend to be affected by low voxel statistics in regions of interest, increasing the sample size would improve their robustness in clinical studies. Therefore, we propose a Generative Adversarial Network (GAN)-based lesion-focused framework for Computed Tomography (CT) image Super-Resolution (SR); for the lesion (i.e., cancer) patch-focused training, we incorporate Spatial Pyramid Pooling (SPP) into GAN-Constrained by the Identical, Residual, and Cycle Learning Ensemble (GAN-CIRCLE). At [Formula: see text] SR, the proposed model achieved better perceptual quality with less blurring than the other considered state-of-the-art SR methods, while producing comparable results at [Formula: see text] SR. We also evaluated the robustness of our model's radiomic feature in terms of quantization on a different lung cancer CT dataset using Principal Component Analysis (PCA). Intriguingly, the most important radiomic features in our PCA-based analysis were the most robust features extracted on the GAN-super-resolved images. These achievements pave the way for the application of GAN-based image Super-Resolution techniques for studies of radiomics for robust biomarker discovery., (© 2021. The Author(s).)

Cancer cells acquire drug resistance through the following stages: nonresistant, pre-resistant, and resistant. Although the molecular mechanism of drug resistance is well investigated, the process of drug resistance acquisition remains largely unknown. Here we elucidate the molecular mechanisms underlying the process of drug resistance acquisition by sequential analysis of gene expression patterns in tamoxifen-treated breast cancer cells. Single-cell RNA-sequencing indicates that tamoxifen-resistant cells can be subgrouped into two, one showing altered gene expression related to metabolic regulation and another showing high expression levels of adhesion-related molecules and histone-modifying enzymes. Pseudotime analysis showed a cell transition trajectory to the two resistant subgroups that stem from a shared pre-resistant state. An ordinary differential equation model based on the trajectory fitted well with the experimental results of cell growth. Based on the established model, it was predicted and experimentally validated that inhibition of transition to both resistant subtypes would prevent the appearance of tamoxifen resistance., (© 2021. The Author(s).)

Alcohol consumption is a major risk factor for premature mortality. Although alcohol control policies are known to impact all-cause mortality rates, the effect that policies have on specific age groups is an important area of research. This study investigates the effect of alcohol control policies implemented in 2009 and 2017 in Lithuania on all-cause mortality rates. All-cause mortality rates (deaths per 100,000 people) were obtained for 2001-2018 by 10-year age groups (20-29, 30-39, 40-49 years, etc.). All-cause mortality rates, independent of macro-level secular trends (e.g., economic trends) were examined. Following a joinpoint analysis to control for secular trends, an interrupted time series analysis showed that alcohol control policies had a significant effect on all-cause mortality rates (p = .018), with the most significant impact occurring among young adults (20-29 and 30-39 years of age). For these age groups, their mortality rate decreased during the 12 months following policy implementation (following the policy in 2009 for those 20-29 years of age, p = .0026, and following the policy in 2017 for those 30-39 years of age, p = .011). The results indicate that alcohol control policy can impact all-cause mortality rates, above and beyond secular trends, and that the impact is significant among young adults., (© 2021. The Author(s).)

Breastfeeding influences the immune system development in infants and may even affect various immunological responses later in life. Breast milk provides a rich source of early nutrition for infant growth and development. However, the presence of certain compounds in breast milk, related to an unhealthy lifestyle or the diet of lactating mothers, may negatively impact infants. Based on a cohort study of atopic dermatitis (AD), we find the presence of damage-associated molecular patterns (DAMPs) activity in the mother's milk. By non-targeted metabolomic analysis, we identify the long-chain saturated fatty acids (LCSFA) as a biomarker DAMPs (+) breast milk samples. Similarly, a mouse model in which breastfed offspring are fed milk high in LCSFA show AD onset later in life. We prove that LCSFA are a type of damage-associated molecular patterns, which initiate a series of inflammatory events in the gut involving type 3 innate lymphoid cells (ILC3s). A remarkable increase in inflammatory ILC3s is observed in the gut, and the migration of these ILC3s to the skin may be potential triggers of AD. Gene expression analysis of ILC3s isolated from the gut reveal upregulation of genes that increase ILC3s and chemokines/chemokine receptors, which may play a role in ILC migration to the skin. Even in the absence of adaptive immunity, Rag1 knockout mice fed a high-LCSFA milk diet develop eczema, accompanied by increased gut ILC3s. We also present that gut microbiota of AD-prone PA milk-fed mice is different from non-AD OA/ND milk-fed mice. Here, we propose that early exposure to LCSFAs in infants may affect the balance of intestinal innate immunity, inducing a highly inflammatory environment with the proliferation of ILC3s and production of interleukin-17 and interleukin-22, these factors may be potential triggers or worsening factors of AD.

We aimed to isolate Acinetobacter baumannii (A. baumannii) from wound infections, determine their resistance and virulence profile, and assess the impact of Silver nanoparticles (AgNPs) on the bacterial growth, virulence and biofilm-related gene expression. AgNPs were synthesized and characterized using TEM, XRD and FTIR spectroscopy. A. baumannii (n = 200) were isolated and identified. Resistance pattern was determined and virulence genes (afa/draBC, cnf1, cnf2, csgA, cvaC, fimH, fyuA, ibeA, iutA, kpsMT II, PAI, papC, PapG II, III, sfa/focDE and traT) were screened using PCR. Biofilm formation was evaluated using Microtiter plate method. Then, the antimicrobial activity of AgNPs was evaluated by the well-diffusion method, growth kinetics and MIC determination. Inhibition of biofilm formation and the ability to disperse biofilms in exposure to AgNPs were evaluated. The effect of AgNPs on the expression of virulence and biofilm-related genes (bap, OmpA, abaI, csuA/B, A1S_2091, A1S_1510, A1S_0690, A1S_0114) were estimated using QRT-PCR. In vitro infection model for analyzing the antibacterial activity of AgNPs was done using a co-culture infection model of A. baumannii with human fibroblast skin cell line HFF-1 or Vero cell lines. A. baumannii had high level of resistance to antibiotics. Most of the isolates harbored the fimH, afa/draBC, cnf1, csgA and cnf2, and the majority of A. baumannii produced strong biofilms. AgNPs inhibited the growth of A. baumannii efficiently with MIC ranging from 4 to 25 µg/ml. A. baumannii showed a reduced growth rate in the presence of AgNPs. The inhibitory activity and the anti-biofilm activity of AgNPs were more pronounced against the weak biofilm producers. Moreover, AgNPs decreased the expression of kpsMII , afa/draBC,bap, OmpA, and csuA/B genes. The in vitro infection model revealed a significant antibacterial activity of AgNPs against extracellular and intracellular A. baumannii. AgNPs highly interrupted bacterial multiplication and biofilm formation. AgNPs downregulated the transcription level of important virulence and biofilm-related genes. Our findings provide an additional step towards understanding the mechanisms by which sliver nanoparticles interfere with the microbial spread and persistence.

To prevent infections associated with medical implants, various antimicrobial silver-coated implant materials have been developed. However, these materials do not always provide consistent antibacterial effects in vivo despite having dramatic antibacterial effects in vitro, probably because the antibacterial effects involve silver-ion-mediated reactive oxygen species generation. Additionally, the silver application process often requires extremely high temperatures, which damage non-metal implant materials. We recently developed a bacteria-resistant coating consisting of hydroxyapatite film on which ionic silver is immobilized via inositol hexaphosphate chelation, using a series of immersion and drying steps performed at low heat. Here we applied this coating to a polymer, polyetheretherketone (PEEK), and analyzed the properties and antibacterial activity of the coated polymer in vitro and in vivo. The ionic silver coating demonstrated significant bactericidal activity and prevented bacterial biofilm formation in vitro. Bio-imaging of a soft tissue infection mouse model in which a silver-coated PEEK plate was implanted revealed a dramatic absence of bacterial signals 10 days after inoculation. These animals also showed a strong reduction in histological features of infection, compared to the control animals. This innovative coating can be applied to complex structures for clinical use, and could prevent infections associated with a variety of plastic implants.

In the ANRS 12174 trial, HIV-exposed uninfected African neonates who received lopinavir-ritonavir (LPV/r) prophylaxis for 1 year exhibited slower growth from birth to week 50 compared with those receiving lamivudine (3TC). We assessed whether this difference in growth persisted over time, and was accompanied by differences in neuropsychological and clinical outcomes. Between February 2017 and February 2018, we conducted a cross-sectional clinical evaluation among former trial participants who completed the 50-week follow-up and who were not HIV-infected. In addition to clinical examination, neuropsychological outcomes were assessed using the tests Kaufman-ABCII, Test of Variables of Attention, Movement Assessment Battery for Children and the Strengths and Difficulties questionnaire, parent version. Of 1101 eligible children, aged 5-7 years, 553 could be traced and analysed (274 in the LPV/r and 279 in the 3TC groups). Growth, clinical and neuropsychological outcomes did not differ between treatment groups. At school age, children exposed to LPV/r and 3TC at birth for 1 year had comparable growth and neuropsychological outcomes without evidence of long-term side-effects of LPV/r. It provides reassuring data on clinical outcomes for all HIV-infected children treated with this antiretroviral drug in early life.