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Additive manufacturing (AM) has transformed the process of shaping refractory metals into complex form factors. This study was undertaken to investigate the AM processing parameters for pure tantalum (Ta) and to understand their influence on the attendant properties. Computational fluid dynamics simulations informed a subset of AM laser parameters that were manufactured and characterized for their porosity and mechanical response. Manufacturing with high energy densities (350-470 J/mm3) increased material density and mechanical strength, but dramatically reduced the ductility owing to the prolific formation of pre-existing edge cracks. While low porosity is typically a key metric for success in AM, the results presented here elucidate that a balance between maximizing bulk material density and minimizing steep thermal gradients during processing is needed to optimize the strength-ductility tradeoff.

The integration of magnetic resonance (MR) imaging and linear accelerators into hybrid treatment systems has made MR-guided radiation therapy a clinical reality. This work aims to evaluate the influence of the Electron Return Effect (ERE) on the dose distributions. This study was conducted using MRIdian (ViewRay, Cleveland, Ohio) system. Monte-Carlo simulations (MCs) and experimental measurements with EBT3 Gafchromic films were performed to investigate the dose distribution in a slab water phantom with and without a 2-cm air gap. Plus, MCs took into account different field sizes and a lung gap. A gamma analysis compared calculated versus measured dose distributions. The MCs have shown an increase of the ERE with the radiation field size both in Percent Depth Dose (PDD) and crossline direction. As concerns to the PDD direction, the smallest field for which there was a significant dose accumulation was 4.15 × 4.15 cm 2 both for air-gap (13.5%) and lung-gap (3.3%). The largest field for which there was a significant dose accumulation was 24.07 × 24.07 cm 2 both for air-gap (39.7%) and lung-gap (4.9%). Instead for the crossline direction, the smallest field for which there was a significant dose accumulation was 2.49 × 2.49 cm 2 both for air-gap (8.6% ) and lung-gap (0.5%). The largest field for which there was a significant dose accumulation was 24.07 × 24.07 cm 2 both for air-gap (46.2%) and lung-gap (4.2%). PDD and crossline profiles showed good agreement with a gamma-passing rate higher than 91.15% for 2%/2 mm. The ERE can be adequately calculated by MC dose calculation platform available in the MRIdian Treatment Planning System. The MCs show an increase of the ERE directly proportional with the radiation field size. Good agreement was observed between the experimental measurements and calculated dose distributions., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Cerebral cavernous malformations (CCMs) are anomalies of the cerebral vasculature. Loss of the CCM proteins CCM1/KRIT1, CCM2, or CCM3/PDCD10 trigger a MAPK-Krüppel-like factor 2 (KLF2) signaling cascade, which induces a pathophysiological pattern of gene expression. The downstream target genes that are activated by KLF2 are mostly unknown. Here we show that Chromobox Protein Homolog 7 (CBX7), component of the Polycomb Repressive Complex 1, contributes to pathophysiological KLF2 signaling during zebrafish cardiovascular development. CBX7/cbx7a mRNA is strongly upregulated in lesions of CCM patients, and in human, mouse, and zebrafish CCM-deficient endothelial cells. The silencing or pharmacological inhibition of CBX7/Cbx7a suppresses pathological CCM phenotypes in ccm2 zebrafish, CCM2-deficient HUVECs, and in a pre-clinical murine CCM3 disease model. Whole-transcriptome datasets from zebrafish cardiovascular tissues and human endothelial cells reveal a role of CBX7/Cbx7a in the activation of KLF2 target genes including TEK, ANGPT1, WNT9, and endoMT-associated genes. Our findings uncover an intricate interplay in the regulation of Klf2-dependent biomechanical signaling by CBX7 in CCM. This work also provides insights for therapeutic strategies in the pathogenesis of CCM., Competing Interests: Disclosure and competing interests statement SA-S holds a European patent (EP4 154 876) related to this study., (© 2024. The Author(s).)

The article 'Ocular Syphilis: An Update (2019)' provides a thorough review of the challenges in diagnosing ocular syphilis. However, our research on 'Dermatological and Ocular Manifestations of Syphilis,' identifies a significant gap in both literature and clinical practice: the lack of recognition of dermatological signs during ophthalmological assessments. Ocular syphilis often mimics other conditions and can remain undiagnosed for months or years. Detecting dermatological signs, such as the characteristic palmar rash of secondary syphilis and extragenital chancres, could prompt earlier investigation and serological testing, reducing unnecessary diagnostic workups and inappropriate management. Early recognition would facilitate timely administration of Penicillin G, helping prevent vision loss, which is often reversible with prompt treatment. We urge Ocular Immunology and Inflammation to highlight the importance of incorporating dermatological assessments in future ocular syphilis publications to improve diagnostic protocols and patient outcomes.

Photodetectors are of great interest in several technological applications thanks to their capability to convert an optical signal into an electrical one through light-matter interactions. In particular, broadband photodetectors based on graphene/silicon heterojunctions could be useful in multiple applications due to their compelling performances. Here, we present a 2D photodiode heterojunction based on a graphene single layer deposited on p-type and n-type Silicon substrates. We report on the electro-optical properties of the device that have been measured in dark and light conditions in a spectral range from 400 nm to 800 nm. The comparison of the device's performance in terms of responsivity and rectification ratio is presented. Raman spectroscopy provides information on the graphene single layer's quality and oxidation. The results showcase the importance of the doping of the silicon substrate to realize an efficient heterojunction that improves the photoresponse, reducing the dark current.

Achieving microscopy with large space-bandwidth products plays a key role in diagnostic imaging and is widely significant in the overall field of clinical practice. Among quantitative microscopy techniques, Fourier Ptychography (FP) provides a wide field of view and high-resolution images, suitable to the histopathological field, but onerous in computational terms. Artificial intelligence can be a solution in this sense. In particular, this research delves into the application of Generative Adversarial Networks (GAN) for the dual-channel complex FP image enhancement of human kidney samples. The study underscores the GANs' efficacy in promoting biological architectures in FP domain, thereby still guaranteeing high resolution and visibility of detailed microscopic structures. We demonstrate successful GAN-based enhanced reconstruction through two strategies: cross-explainability and expert survey. The cross-explainability is evaluated through the comparison of explanation maps for both real and imaginary components underlining its robustness. This comparison further shows that their interplay is pivotal for accurate reconstruction without hallucinations. Secondly, the enhanced reconstruction accuracy and effectiveness in a clinical workflow are confirmed through a two-step survey conducted with nephrologists., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Authors M.V., V.B., L.M., P.M., P.Fe., P.Fi., F.B., and R.T. declare no financial or any other competing interest associated with the present manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine whether small, incidentally detected testicular lesions can be safely followed up, by assessing growth rate and volume threshold for benign vs. malignant lesions., Methods: This retrospective observational study includes a consecutive series of 130 testicular incidentalomas < 1 cm and with negative tumour markers identified from October 2001 to November 2022, which were initially followed up with ultrasound. A total of 39 cases proceeded to surgery during the study period, either due to lesion growth (n = 28) or patient preference/recommendation by the referring urologist (n = 11). For the lesions that were growing, specific growth rate (SGR) and doubling time (DT) were calculated assuming an exponential growth pattern. In addition, the velocity of increase of the average diameter (∆D av ) and of the maximum diameter (∆D max ) were calculated., Results: Of the 130 nodules that were initially followed up, six disappeared, eight were reduced in size, eighty-eight were stable, and twenty-eight increased in size. For operated nodules all 18 malignant tumours, 8/9 benign tumours, and 2/12 surgically proved non-neoplastic lesions were growing. The best cut-off values of the growth indicators to differentiate between malignant and non-malignant histology were 3.47 × 10 -3 %volume/day, ≤ 179 days, > 10 × 10 -3  mm/day, and > 5 × 10 -3  mm/day for SGR, DT, ∆D max , ∆D av , respectively., Conclusions: Malignant and non-malignant small incidentalomas can be effectively differentiated based on growing parameters, even though overlap exists. An increase of the maximum diameter of about 1 mm and 2 mm in three months and in six months, respectively, suggests malignancy., Clinical Relevance Statement: Growing parameters allow an educated assessment of benign and malignant small testicular incidentalomas. Non-aggressive management is justified and safe when follow-up includes self-examination and tumour marker assessment to reduce the risk of interval tumour growth., Key Points: Small, non-palpable and asymptomatic testicular nodules < 1 cm are unexpectedly discovered during scrotal ultrasound. Growth indicators estimate the potential malignancy, even though overlap with non-malignant lesions exists. Non-growing incidentalomas can be safely followed up., (© 2024. The Author(s).)

Camelid single-domain antibodies (VHH) represent a promising class of immunobiologicals for therapeutic applications due to their remarkable stability, specificity, and therapeutic potential. To enhance the effectiveness of antivenoms for snakebites, various methods have been explored to address limitations associated with serum therapy, particularly focusing on mitigating local damage and ensuring sustainable production. Our study aimed to characterize the pharmacological profile and neutralization capacity of anti-Phospholipase A 2 (PLA 2 ) monomeric VHH (Genbank accessions: KC329718). Using a post-envenoming mouse model, we used intravital microscopy to assess leukocyte influx, measured CK and LDH levels, and conducted a histopathology analysis to evaluate VHH KC329718's ability to neutralize myotoxic activity. Our findings demonstrated that VHH KC329718 exhibited heterogeneous distribution in muscle tissue. Treatment with VHH KC329718 reduced leukocyte influx caused by BthTX-I (a Lys-49 PLA2) by 28 %, as observed through intravital microscopy. When administered at a 1:10 ratio [venom or toxin:VHH (w/w)], VHH KC329718 significantly decreased myotoxicity, resulting in a 35-40 % reduction in CK levels from BthTX-I and BthTX-II (an Asp-49 PLA 2 ) and a 60 % decrease in CK levels from B. jararacussu venom. LDH levels also showed reductions of 60%, 80%, and 60% induced by BthTX-I, BthTX-II, and B. jararacussu venom, respectively. Histological analysis confirmed the neutralization potential, displaying a significant reduction in tissue damage and inflammatory cell count in mice treated with VHH KC329718 post B. jararacussu venom inoculation. This study underscores the potential of monomeric anti-PLA 2 VHH in mitigating myotoxic effects, suggesting a promising avenue for the development of new generation antivenoms to address current therapeutic limitations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients' safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts' opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery., (© 2024. The Author(s).)

Breast cancer is one of the most spread and monitored pathologies in high-income countries. After breast biopsy, histological tissue is stored in paraffin, sectioned and mounted. Conventional inspection of tissue slides under benchtop light microscopes involves paraffin removal and staining, typically with H&E. Then, expert pathologists are called to judge the stained slides. However, paraffin removal and staining are operator-dependent, time and resources consuming processes that can generate ambiguities due to non-uniform staining. Here we propose a novel method that can work directly on paraffined stain-free slides. We use Fourier Ptychography as a quantitative phase-contrast microscopy method, which allows accessing a very wide field of view (i.e., mm 2 ) in one single image while guaranteeing high lateral resolution (i.e., 0.5 µm). This imaging method is multi-scale, since it enables looking at the big picture, i.e. the complex tissue structure and connections, with the possibility to zoom-in up to the single-cell level. To handle this informative image content, we introduce elements of fractal geometry as multi-scale analysis method. We show the effectiveness of fractal features in describing and classifying fibroadenoma and breast cancer tissue slides from ten patients with very high accuracy. We reach 94.0 ± 4.2% test accuracy in classifying single images. Above all, we show that combining the decisions of the single images, each patient's slide can be classified with no error. Besides, fractal geometry returns a guide map to help pathologist to judge the different tissue portions based on the likelihood these can be associated to a breast cancer or fibroadenoma biomarker. The proposed automatic method could significantly simplify the steps of tissue analysis and make it independent from the sample preparation, the skills of the lab operator and the pathologist., Competing Interests: The authors have no conflict of interests to declare., (© 2024 The Authors.)

Background: In May of 2022, an mpox (formerly known as monkeypox) outbreak was reported from countries where the disease is not endemic, rising worldwide concern. Malta, the smallest European Union member state, faced unique challenges, with high infection rates compared to the rest of Europe. The aim of the study is to describe the clinical characteristics, diagnostic challenges, and unique demographics of mpox patients diagnosed in Malta., Methods: This is a retrospective analysis of medical records of all mpox cases recorded from May to September 2022. Demographic data, sexual behaviors and practices, travel history, comorbidities, and HIV status were investigated., Results: In the study period, we recorded 33 mpox cases, 97% of them were male, in the age group 30-39 (39%). Ninety percent were gay or bisexual men and 76% non-Maltese. The most common clinical presentations included skin rash (78%), lymphadenopathy (71%), anogenital lesions (67%), and fever (67%). Twenty-seven percent of the patients were people living with HIV. In terms of coinfection with STIs, 27% of patients tested positive for gonorrhea, 12% for syphilis, 15% for chlamydia, 9% for herpes simplex virus, and 3% for hepatitis C virus., Conclusion: The results shed light on unique challenges faced by the local sexual health clinic and call for more resources in response to the global emerging of infectious diseases., (© 2023 the International Society of Dermatology.)

Background: The purpose of this study is to measure the effects of stereotactic MR-guided adaptive radiotherapy (SMART) for rectal cancer patients in terms of early toxicity and pathological response., Materials and Methods: For this prospective pilot study, patients diagnosed with locally advanced rectal cancer (LARC) with positive lymph node clinical staging underwent SMART on rectal lesion and mesorectum using hybrid MR-Linac (MRIdian ViewRay). Dose prescription at 80% isodose for the rectal lesion and mesorectum was 40 Gy (8 Gy/fr) and 25 Gy (5 Gy/fr), respectively, delivered on 5 days (3 fr/week). Response assessment by MRI was performed 3 weeks after SMART, then patients fit for surgery underwent total mesorectal excision. Primary endpoint was evaluation of adverse effect of radiotherapy. Secondary endpoint was pathological complete response rate. Early toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0)., Results: From October 2020 to January 2022, twenty patients underwent rectal SMART. No grade 3-5 toxicity was recorded. Twelve patients were eligible for total mesorectal excision (TME). Mean interval between the completion of SMART and surgery was 4 weeks. Pathological downstaging occurred in all patients; rate of pathological complete response (pCR) was 17%. pCR occurred with a prolonged time to surgery (> 7 weeks)., Conclusion: To our knowledge, this is the first study to use stereotactic radiotherapy for primary rectal cancer. SMART for rectal cancer is well tolerated and effective in terms of tumor regression, especially if followed by delayed surgery., Competing Interests: Conflict of interest None declared., (© 2023 Greater Poland Cancer Centre.)

The trend toward personalized medicine necessitates drawing conclusions from descriptive indexes of physiopathological states estimated from individual recordings of biomedical signals, using statistical analyses that focus on subject-specific differences between experimental conditions. In this context, the present work introduces an approach to assess functional connectivity in brain and physiologic networks by pairwise information-theoretic measures of coupling between signals, whose significance and variations between conditions are statistically validated on a single-subject basis through the use of surrogate and bootstrap data analyses. The approach is illustrated on single-subject recordings of (i) resting-state functional magnetic resonance imaging (rest-fMRI) signals acquired in a pediatric patient with hepatic encephalography associated to a portosystemic shunt and undergoing liver vascular shunt correction, and of (ii) cardiovascular and cerebrovascular time series acquired at rest and during head-up tilt in a subject suffering from orthostatic intolerance.

Many countries are facing an aging population. As people live longer, surgeons face the prospect of operating on increasingly older patients. Traditional teaching is that with older age, these patients face an increased risk of mortality and morbidity, even to a level deemed too prohibitive for surgery. However, this is not always true. An active 90-year-old patient can be much fitter than an overweight, sedentary 65-year-old patient with comorbidities. Recent literature shows that frailty-an age-related cumulative decline in multiple physiological systems, is therefore a better predictor of mortality and morbidity than chronological age alone. Despite recognition of frailty as an important tool in identifying vulnerable surgical patients, many surgeons still shun objective tools. The aim of this position paper was to perform a review of the existing literature and to provide recommendations on emergency laparotomy and in frail patients. This position paper was reviewed by an international expert panel composed of 37 experts who were asked to critically revise the manuscript and position statements. The position paper was conducted according to the WSES methodology. We shall present the derived statements upon which a consensus was reached, specifying the quality of the supporting evidence and suggesting future research directions., (© 2023. The Author(s).)

Objectives: Malignant pleural mesothelioma (MPM) is an aggressive disease with grim prognosis due to lack of effective treatment options. Disease prediction in association with early diagnosis may both contribute to improved MPM survival. Inflammation and autophagy are two processes associated with asbestos-induced transformation. We evaluated the level of two autophagic factors ATG5 and HMGB1, microRNAs (miRNAs) such as miR-126 and miR-222, and the specific biomarker of MPM, soluble mesothelin related proteins (Mesothelin) in asbestos-exposed individuals, MPM patients, and healthy subjects. The performance of these markers in detecting MPM was investigated in pre-diagnostic samples of asbestos-subjects who developed MPM during the follow-up and compared for the three groups., Results: The ATG5 best distinguished the asbestos-exposed subjects with and without MPM, while miR-126 and Mesothelin were found as a significant prognostic biomarker for MPM. ATG5 has been identified as an asbestos-related biomarker that can help to detect MPM with high sensitivity and specificity in pre-diagnostic samples for up to two years before diagnosis. To utilize this approach practically, higher number of cases has to be tested in order to give the combination of the two markers sufficient statistical power. Performance of the biomarkers should be confirmed by testing their combination in an independent cohort with pre-diagnostic samples., (© 2023. The Author(s).)

Microplastic (MP) pollution is seriously threatening the environmental health of the world, which has accelerated the development of new identification and characterization methods. Digital holography (DH) is one of the emerging tools to detect MPs in a high-throughput flow. Here, we review advances in MP screening by DH. We examine the problem from both the hardware and software viewpoints. Automatic analysis based on smart DH processing is reported by highlighting the role played by artificial intelligence for classification and regression tasks. In this framework, the continuous development and availability in recent years of field-portable holographic flow cytometers for water monitoring also is discussed.

Extremely low-frequency electromagnetic fields (ELF-MF) can modify the cell viability and regulatory processes of some cell types, including breast cancer cells. Breast cancer is a multifactorial disease where a role for ELF-MF cannot be excluded. ELF-MF may influence the biological properties of breast cells through molecular mechanisms and signaling pathways that are still unclear. This study analyzed the changes in the cell viability, cellular morphology, oxidative stress response and alteration of proteomic profile in breast cancer cells (MDA-MB-231) exposed to ELF-MF (50 Hz, 1 mT for 4 h). Non-tumorigenic human breast cells (MCF-10A) were used as control cells. Exposed MDA-MB-231 breast cancer cells increased their viability and live cell number and showed a higher density and length of filopodia compared with the unexposed cells. In addition, ELF-MF induced an increase of the mitochondrial ROS levels and an alteration of mitochondrial morphology. Proteomic data analysis showed that ELF-MF altered the expression of 328 proteins in MDA-MB-231 cells and of 242 proteins in MCF-10A cells. Gene Ontology term enrichment analysis demonstrated that in both cell lines ELF-MF exposure up-regulated the genes enriched in "focal adhesion" and "mitochondrion". The ELF-MF exposure decreased the adhesive properties of MDA-MB-231 cells and increased the migration and invasion cell abilities. At the same time, proteomic analysis, confirmed by Real Time PCR, revealed that transcription factors associated with cellular reprogramming were upregulated in MDA-MB-231 cells and downregulated in MCF-10A cells after ELF-MF exposure. MDA-MB-231 breast cancer cells exposed to 1 mT 50 Hz ELF-MF showed modifications in proteomic profile together with changes in cell viability, cellular morphology, oxidative stress response, adhesion, migration and invasion cell abilities. The main signaling pathways involved were relative to focal adhesion, mitochondrion and cellular reprogramming., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The development of ultrasensitive analytical detection methods for organophosphorus pesticides such as dimethoate (DMT) plays a key role in healthy food production. DMT is an inhibitor of acetylcholinesterase (AChE), which can lead to the accumulation of acetylcholine and result in symptoms related to the autonomous and central nervous systems. Herein, we report the first spectroscopic and electrochemical study on template removal after an imprinting process from a polypyrrole-based molecularly imprinted polymer (PPy-MIP) film for the detection of DMT. Several template removal procedures were tested and evaluated using X-ray photoelectron spectroscopy. The most effective procedure was achieved in 100 mM NaOH. The proposed DMT PPy-MIP sensor exhibits a limit of detection of (8 ± 2) × 10 -12 M.

Kidney microscopy is a mainstay in studying the morphological structure, physiology and pathology of kidney tissues, as histology provides important results for a reliable diagnosis. A microscopy modality providing at same time high-resolution images and a wide field of view could be very useful for analyzing the whole architecture and the functioning of the renal tissue. Recently, Fourier Ptychography (FP) has been proofed to yield images of biology samples such as tissues and in vitro cells while providing high resolution and large field of view, thus making it a unique and attractive opportunity for histopathology. Moreover, FP offers tissue imaging with high contrast assuring visualization of small desirable features, although with a stain-free mode that avoids any chemical process in histopathology. Here we report an experimental measuring campaign for creating the first comprehensive and extensive collection of images of kidney tissues captured by this FP microscope. We show that FP microscopy unlocks a new opportunity for the physicians to observe and judge renal tissue slides through the novel FP quantitative phase-contrast microscopy. Phase-contrast images of kidney tissue are analyzed by comparing them with the corresponding renal images taken under a conventional bright-field microscope both for stained and unstained tissue samples of different thicknesses. In depth discussion on the advantages and limitations of this new stain-free microscopy modality is reported, showing its usefulness over the classical light microscopy and opening a potential route for using FP in clinical practice for histopathology of kidney., Competing Interests: Authors MV, VBi, LM, PM, and PF were employed by the company National Research Council (CNR) of Italy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Valentino, Bianco, Miccio, Memmolo, Brancato, Libretti, Gambacorta, Salvatore and Ferraro.)

Background: The exposure of breast cancer to extremely low frequency magnetic fields (ELF-MFs) results in various biological responses. Some studies have suggested a possible cancer-enhancing effect, while others showed a possible therapeutic role. This study investigated the effects of in vitro exposure to 50 Hz ELF-MF for up to 24 h on the viability and cellular response of MDA-MB-231 and MCF-7 breast cancer cell lines and MCF-10A breast cell line., Methods and Results: The breast cell lines were exposed to 50 Hz ELF-MF at flux densities of 0.1 mT and 1.0 mT and were examined 96 h after the beginning of ELF-MF exposure. The duration of 50 Hz ELF-MF exposure influenced the cell viability and proliferation of both the tumor and nontumorigenic breast cell lines. In particular, short-term exposure (4-8 h, 0.1 mT and 1.0 mT) led to an increase in viability in breast cancer cells, while long and high exposure (24 h, 1.0 mT) led to a decrease in viability and proliferation in all cell lines. Cancer and normal breast cells exhibited different responses to ELF-MF. Mitochondrial membrane potential and reactive oxygen species (ROS) production were altered after ELF-MF exposure, suggesting that the mitochondria are a probable target of ELF-MF in breast cells., Conclusions: The viability of breast cells in vitro is influenced by ELF-MF exposure at magnetic flux densities compatible with the limits for the general population and for workplace exposures. The effects are apparent after 96 h and are related to the ELF-MF exposure time., (© 2022. The Author(s).)

Locus coeruleus (LC) neurons, with their extensive innervations throughout the brain, control a broad range of physiological processes. Several ion channels have been characterized in LC neurons that control intrinsic membrane properties and excitability. However, ERG ( ether-à-go-go-related gene ) K + channels that are particularly important in setting neuronal firing rhythms and automaticity have not as yet been discovered in the LC. Moreover, the neurophysiological and pathophysiological roles of ERG channels in the brain remain unclear despite their expression in several structures. By performing immunohistochemical investigations, we found that ERG-1A, ERG-1B, ERG-2 and ERG-3 are highly expressed in the LC neurons of mice. To examine the functional role of ERG channels, current-clamp recordings were performed on mouse LC neurons in brain slices under visual control. ERG channel blockade by WAY-123,398, a class III anti-arrhythmic agent, increased the spontaneous firing activity and discharge irregularity of LC neurons. Here, we have shown the presence of distinct ERG channel subunits in the LC which play an imperative role in modulating neuronal discharge patterns. Thus, we propose that ERG channels are important players behind the changes in, and/or maintenance of, LC firing patterns that are implicated in the generation of different behaviors and in several disorders.

The packaging of specific mRNAs into ribonucleoprotein granules called germ granules is required for germline proliferation and maintenance. During Drosophila germ granule development, mRNAs such as nanos (nos) and polar granule component (pgc) localize to germ granules through a stochastic seeding and self-recruitment process that generates homotypic clusters: aggregates containing multiple copies of a specific transcript. Germ granules vary in mRNA composition with respect to the different transcripts that they contain and their quantity. However, what influences germ granule mRNA composition during development is unclear. To gain insight into how germ granule mRNA heterogeneity arises, we created a computational model that simulates granule development. Although the model includes known mechanisms that were converted into mathematical representations, additional unreported mechanisms proved to be essential for modeling germ granule formation. The model was validated by predicting defects caused by changes in mRNA and protein abundance. Broader application of the model was demonstrated by quantifying nos and pgc localization efficacies and the contribution that an element within the nos 3' untranslated region has on clustering. For the first time, a mathematical representation of Drosophila germ granule formation is described, offering quantitative insight into how mRNA compositions arise while providing a new tool for guiding future studies., (Copyright © 2022 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

A reliable diagnosis and accurate monitoring are pivotal steps for treatment and prevention of COVID-19. Chest computed tomography (CT) has been considered a crucial diagnostic imaging technique for the injury assessment of the viral pneumonia. Furthermore, the automatization of the segmentation methods for lung alterations helps to speed up the diagnosis and lighten radiologists' workload. Considering the assiduous pathology monitoring, ultra-low dose (ULD) chest CT protocols have been implemented to drastically reduce the radiation burden. Unfortunately, the available AI technologies have not been trained on ULD-CT data and validated and their applicability deserves careful evaluation. Therefore, this work aims to compare the results of available AI tools (BCUnet, CORADS AI, NVIDIA CLARA Train SDK and CT Pneumonia Analysis) on a dataset of 73 CT examinations acquired both with conventional dose (CD) and ULD protocols. COVID-19 volume percentage, resulting from each tool, was statistically compared. This study demonstrated high comparability of the results on CD-CT and ULD-CT data among the four AI tools, with high correlation between the results obtained on both protocols (R > .68, P < .001, for all AI tools)., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Micron size fiber fragments (MFFs), both natural and synthetic, are ubiquitous in our life, especially in textile clothes, being necessary in modern society. In the Earth's aquatic ecosystem, microplastic fibers account for ~91% of microplastic pollution, thus deserving notable attention as one of the most alarming ecological problems. Accurate automatic identification of MFFs discharges in specific upstream locations is highly demanded. Computational microscopy based on Digital Holography (DH) and machine learning has been demonstrated to identify microplastics in respect to microalgae. However, DH is a non-specific optical tool, meaning it cannot distinguish different types of plastic materials. On the other hand, materials-specific assessments are pivotal to establish the environmental impact of different textile products and production processes. Spectroscopic assays can be employed to identify microplastics for their intrinsic specificity, although they are generally low-throughput and require large concentrations to enable effective measurements. Conversely, MFFs are usually finely dispersed within a water sample. Here we rely on a polarization-resolved holographic flow cytometer in a Lab-on-Chip (LoC) platform for analysing MFFs. We demonstrate that two important objectives can be achieved, i.e. adding material specificity through polarization analysis while operating in a microfluidic stream modality. Through a machine learning numerical pipeline, natural fibers (i.e. cotton and wool) can be clearly separated from synthetic microfilaments, namely PA6, PA6.6, PET, PP. Moreover, the proposed system can accurately distinguish between different polymers under investigation, thus fulfilling the specificity goal. We extract and select different features from amplitude, phase and birefringence maps retrieved from the digital holograms. These are shown to typify MFFs without the need for sample pre-treatment or large concentrations. The simplicity of the DH method for identifying MFFs in LoC-based flow cytometers could promote the use of polarization resolved field-portable analysis systems suitable for studying pollution caused by washing processes of synthetic textiles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)