East Asian summer monsoon delivers large abundances of very-short-lived organic chlorine substances to the lower stratosphere.

Deep convection in the Asian summer monsoon is a significant transport process for lifting pollutants from the planetary boundary layer to the tropopause level. This process enables efficient injection into the stratosphere of reactive species such as chlorinated very-short-lived substances (Cl-VSLSs) that deplete ozone. Past studies of convective transport associated with the Asian summer monsoon have focused mostly on the south Asian summer monsoon. Airborne observations reported in this work identify the East Asian summer monsoon convection as an effective transport pathway that carried record-breaking levels of ozone-depleting Cl-VSLSs (mean organic chlorine from these VSLSs ~500 ppt) to the base of the stratosphere. These unique observations show total organic chlorine from VSLSs in the lower stratosphere over the Asian monsoon tropopause to be more than twice that previously reported over the tropical tropopause. Considering the recently observed increase in Cl-VSLS emissions and the ongoing strengthening of the East Asian summer monsoon under global warming, our results highlight that a reevaluation of the contribution of Cl-VSLS injection via the Asian monsoon to the total stratospheric chlorine budget is warranted.

Molecular portraits of patients with intrahepatic cholangiocarcinoma who diverge as rapid progressors or long survivors on chemotherapy.

OBJECTIVE: Cytotoxic agents are the cornerstone of treatment for patients with advanced intrahepatic cholangiocarcinoma (iCCA), despite heterogeneous benefit. We hypothesised that the pretreatment molecular profiles of diagnostic biopsies can predict patient benefit from chemotherapy and define molecular bases of innate chemoresistance. DESIGN: We identified a cohort of advanced iCCA patients with comparable baseline characteristics who diverged as extreme outliers on chemotherapy (survival <6 m in rapid progressors, RP; survival >23 m in long survivors, LS). Diagnostic biopsies were characterised by digital pathology, then subjected to whole-transcriptome profiling of bulk and geospatially macrodissected tissue regions. Spatial transcriptomics of tumour-infiltrating myeloid cells was performed using targeted digital spatial profiling (GeoMx). Transcriptome signatures were evaluated in multiple cohorts of resected cancers. Signatures were also characterised using in vitro cell lines, in vivo mouse models and single cell RNA-sequencing data. RESULTS: Pretreatment transcriptome profiles differentiated patients who would become RPs or LSs on chemotherapy. Biologically, this signature originated from altered tumour-myeloid dynamics, implicating tumour-induced immune tolerogenicity with poor response to chemotherapy. The central role of the liver microenviroment was confrmed by the association of the RPLS transcriptome signature with clinical outcome in iCCA but not extrahepatic CCA, and in liver metastasis from colorectal cancer, but not in the matched primary bowel tumours. CONCLUSIONS: The RPLS signature could be a novel metric of chemotherapy outcome in iCCA. Further development and validation of this transcriptomic signature is warranted to develop precision chemotherapy strategies in these settings.

Targeting the Antifungal Activity of Carbon Dots against Candida albicans Biofilm Formation by Tailoring Their Surface Functional Groups.

Carbon dots (CDs) are an emerging class of carbon nanoparticles, which for their characteristics have found applications in many fields such as catalysis, materials and biomedicine. Within this context, the application of CDs as antibacterial agents has received much attention in very recent years, while their use as antifungal nanoparticles has been scarcely investigated. Here we report a systematic investigation of the surface functional groups of CDs to study their influence on these nanoparticles' against Candida albicans. Three classes of CDs have been synthesised and fully characterized. A thorough in vitro and in vivo biological screening against C. albicans was performed to test their antifungal, antiadhesion and antibiofilm formation activities. Moreover, the interaction with C. albicans cells was investigated by microscopic analysis. Our results evidence how the presence of a positively polarised surface results crucial for the internalization into COS-7 cells. Positively charged nanoparticles were also able to inhibit adhesion and biofilm formation, to interact with the cellular membrane of C. albicans, and to increase the survival of G. mellonella infected larvae after the injection with positive nanoparticles. The antifungal activity of CDs and their extremely low toxicity may represent a new strategy to combat infections sustained by C.albicans.

The Role of Deep Learning and Gait Analysis in Parkinson's Disease: A Systematic Review.

Parkinson's disease (PD) is the second most common movement disorder in the world. It is characterized by motor and non-motor symptoms that have a profound impact on the independence and quality of life of people affected by the disease, which increases caregivers' burdens. The use of the quantitative gait data of people with PD and deep learning (DL) approaches based on gait are emerging as increasingly promising methods to support and aid clinical decision making, with the aim of providing a quantitative and objective diagnosis, as well as an additional tool for disease monitoring. This will allow for the early detection of the disease, assessment of progression, and implementation of therapeutic interventions. In this paper, the authors provide a systematic review of emerging DL techniques recently proposed for the analysis of PD by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Scopus, PubMed, and Web of Science databases were searched across an interval of six years (between 2018, when the first article was published, and 2023). A total of 25 articles were included in this review, which reports studies on the movement analysis of PD patients using both wearable and non-wearable sensors. Additionally, these studies employed DL networks for classification, diagnosis, and monitoring purposes. The authors demonstrate that there is a wide employment in the field of PD of convolutional neural networks for analyzing signals from wearable sensors and pose estimation networks for motion analysis from videos. In addition, the authors discuss current difficulties and highlight future solutions for PD monitoring and disease progression.

Healthcare Risk Management and Monitoring of patient falls in Italian National Service. The experience of a Local Health Authority.

Falls are a widespread concern in hospitals settings. In Italy, falls are the fourth frequent damage claim type after surgical, diagnostic and therapeutic error and 90% of falls are avoidable. The first necessary action for the prevention of falls consists in identifying the possible risk factors, in relation to the characteristics of the patient and those of the environment and the structure that hosts him, in terms of safety, organization and adequacy of the process welfare. In this work we wanted to evaluate the extent, frequency and characteristics of the phenomenon of falls in the population hospitalized at the Local Health Authority called "Roma 2", with the aim of analyzing the critical issues to allow the identification of possible preventive and improvement interventions as well as reducing the risk of falls.

Impact of the Number of Needle Tip Bevels on the Exerted Forces and Energy in Insulin Pen Injections.

Patients affected with type 1 diabetes and a non-negligible number of patients with type 2 diabetes are insulin dependent. Both the injection technique and the choice of the most suitable needle are fundamental for allowing them to have a good injection experience. The needles may differ in several parameters, from the length and diameter, up to the forces required to perform the injection and to some geometrical parameters of the needle tip (e.g., number of facets or bevels). The aim of the research is to investigate whether an increased number of bevels could decrease forces and energy involved in the insertion-extraction cycle, thus potentially allowing patients to experience lower pain. Two needle variants, namely, 31 G × 5 mm and 32 G × 4 mm, are considered, and experimental tests are carried out to compare 3-bevels with 5-bevels needles for both the variants. The analysis of the forces and energy for both variants show that the needles with 5 bevels require a statistically significant lower drag or sliding force (p-value = 0.040 for the 31 G × 5 mm needle and p-value < 0.001 for 32 G × 4 mm), extraction force (p-value < 0.001 for both variants), and energy (p-value < 0.001 for both variants) during the insertion-extraction cycle. As a result, 3-bevels needles do not have the same functionality of 5-bevels needles, show lower capacity of drag and extraction, and can potentially be related to more painful injection experience for patients.

Identification of a Gait Pattern for Detecting Mild Cognitive Impairment in Parkinson's Disease.

The aim of this study was to determine a gait pattern, i.e., a subset of spatial and temporal parameters, through a supervised machine learning (ML) approach, which could be used to reliably distinguish Parkinson's Disease (PD) patients with and without mild cognitive impairment (MCI). Thus, 80 PD patients underwent gait analysis and spatial-temporal parameters were acquired in three different conditions (normal gait, motor dual task and cognitive dual task). Statistical analysis was performed to investigate the data and, then, five ML algorithms and the wrapper method were implemented: Decision Tree (DT), Random Forest (RF), Naïve Bayes (NB), Support Vector Machine (SVM) and K-Nearest Neighbour (KNN). First, the algorithms for classifying PD patients with MCI were trained and validated on an internal dataset (sixty patients) and, then, the performance was tested by using an external dataset (twenty patients). Specificity, sensitivity, precision, accuracy and area under the receiver operating characteristic curve were calculated. SVM and RF showed the best performance and detected MCI with an accuracy of over 80.0%. The key features emerging from this study are stance phase, mean velocity, step length and cycle length; moreover, the major number of features selected by the wrapper belonged to the cognitive dual task, thus, supporting the close relationship between gait dysfunction and MCI in PD.

Agreement between Optoelectronic System and Wearable Sensors for the Evaluation of Gait Spatiotemporal Parameters in Progressive Supranuclear Palsy.

The use of wearable sensors for calculating gait parameters has become increasingly popular as an alternative to optoelectronic systems, currently recognized as the gold standard. The objective of the study was to evaluate the agreement between the wearable Opal system and the optoelectronic BTS SMART DX system for assessing spatiotemporal gait parameters. Fifteen subjects with progressive supranuclear palsy walked at their self-selected speed on a straight path, and six spatiotemporal parameters were compared between the two measurement systems. The agreement was carried out through paired data test, Passing Bablok regression, and Bland-Altman Analysis. The results showed a perfect agreement for speed, a very close agreement for cadence and cycle duration, while, in the other cases, Opal system either under- or over-estimated the measurement of the BTS system. Some suggestions about these misalignments are proposed in the paper, considering that Opal system is widely used in the clinical context.

Percutaneous vacuum-assisted excision (VAE) of breast lesions of uncertain malignant potential (B3 lesions): a preliminary single-centre Italian experience.

PURPOSE: In recent years vacuum-assisted excision (VAE) has been described as an alternative treatment for some B3 lesions. This study aims to assess the effectiveness of using VAE to manage selected B3 lesions by quantifying the number of B3 lesions undergoing VAE, the malignant upgrade rate, and the complications encountered. MATERIALS AND METHODS: Our department evaluated all B3 lesions diagnosed between January 2019 and October 2021 and treated them with VAE. The data were collected during the initial biopsy and final histology based on VAE image guidance, also considering initial lesions and complications. The exclusion criteria were: B3 lesion of size > 20 mm, presence of a concomitant malignant lesion, lesion < 5.0 mm distant from the skin, nipple or pectoral muscle, phyllodes tumours or indeterminate B3 lesions. Lesions that upgraded to malignancy underwent surgical excision, while benign lesions performed radiological follow-ups. RESULTS: From 416 B3 lesions diagnosed, 67 (16.1%) underwent VAE. VAE was performed under X-ray (50/67) or ultrasound guidance (17/67). Five cases (7.5%) upgraded to a malignant lesion, 2 ADH, 2 LIN and one papillary lesion that underwent surgery. No malignancy or new lesions has occurred at the site of the VAE, with an average radiological follow-up of 14.9 months. CONCLUSIONS: VAE could be a safe and effective pathway for managing selected B3 lesions. Lesions initially subjected to CNB with ADH and LN outcome, before undergoing VAE, should perform a VAB for better tissue characterization and management.

Statistical Analysis and Kinematic Assessment of Upper Limb Reaching Task in Parkinson's Disease.

The impact of neurodegenerative disorders is twofold; they affect both quality of life and healthcare expenditure. In the case of Parkinson's disease, several strategies have been attempted to support the pharmacological treatment with rehabilitation protocols aimed at restoring motor function. In this scenario, the study of upper limb control mechanisms is particularly relevant due to the complexity of the joints involved in the movement of the arm. For these reasons, it is difficult to define proper indicators of the rehabilitation outcome. In this work, we propose a methodology to analyze and extract an ensemble of kinematic parameters from signals acquired during a complex upper limb reaching task. The methodology is tested in both healthy subjects and Parkinson's disease patients (N = 12), and a statistical analysis is carried out to establish the value of the extracted kinematic features in distinguishing between the two groups under study. The parameters with the greatest number of significances across the submovements are duration, mean velocity, maximum velocity, maximum acceleration, and smoothness. Results allowed the identification of a subset of significant kinematic parameters that could serve as a proof-of-concept for a future definition of potential indicators of the rehabilitation outcome in Parkinson's disease.

Overcrowding analysis in emergency department through indexes: a single center study.

INTRODUCTION: Overcrowding in the Emergency Department (ED) is one of the major issues that must be addressed in order to improve the services provided in emergency circumstances and to optimize their quality. As a result, in order to help the patients and professionals engaged, hospital organizations must implement remedial and preventative measures. Overcrowding has a number of consequences, including inadequate treatment and longer hospital stays; as a result, mortality and the average duration of stay in critical care units both rise. In the literature, a number of indicators have been used to measure ED congestion. EDWIN, NEDOCS and READI scales are considered the most efficient ones, each of which is based on different parameters regarding the patient management in the ED. METHODS: In this work, EDWIN Index and NEDOCS Index have been calculated every hour for a month period from February 9th to March 9th, 2020 and for a month period from March 10th to April 9th, 2020. The choice of the period is related to the date of the establishment of the lockdown in Italy due to the spread of Coronavirus; in fact on 9 March 2020 the Italian government issued the first decree regarding the urgent provisions in relation to the COVID-19 emergency. Besides, the Pearson correlation coefficient has been used to evaluate how much the EDWIN and NEDOCS indexes are linearly dependent. RESULTS: EDWIN index follows a trend consistent with the situation of the first lockdown period in Italy, defined by extreme limitations imposed by Covid-19 pandemic. The 8:00-20:00 time frame was the most congested, with peak values between 8:00 and 12:00. on the contrary, in NEDOCS index doesn't show a trend similar to the EDWIN one, resulting less reliable. The Pearson correlation coefficient between the two scales is 0,317. CONCLUSION: In this study, the EDWIN Index and the NEDOCS Index were compared and correlated in order to assess their efficacy, applying them to the case study of the Emergency Department of "San Giovanni di Dio e Ruggi d'Aragona" University Hospital during the Covid-19 pandemic. The EDWIN scale turned out to be the most realistic model in relation to the actual crowding of the ED subject of our study. Besides, the two scales didn't show a significant correlation value.

Nuclear Magnetic Resonance Reveals Molecular Species in Carbon Nanodot Samples Disclosing Flaws.

Carbon nanodots are currently one of the hot topics in the nanomaterials world, due to their accessible synthesis and promising features. However, the purification of these materials is still a critical aspect, especially for syntheses involving molecular precursors. Indeed, the presence of unreacted species or small organic molecules formed during solvothermal treatments can affect the properties of the synthesized nanomaterials. To illustrate the extreme importance of this issue, we present two case studies in which insufficient purification results in misleading conclusions regarding the chiral and fluorescent properties of the investigated materials. Key to identify molecular species is the use of nuclear magnetic resonance, which proves to be an effective tool. Our work highlights the need to include nuclear magnetic resonance as a standard characterization technique for carbon-based nanomaterials, to minimize the risk of observing properties that arise from molecular species, rather than the target carbon nanodots.

Transfer of Axial Chirality to the Nanoscale Endows Carbon Nanodots with Circularly Polarized Luminescence.

We report the synthesis, purification and characterization of chiral carbon nanodots starting from atropoisomeric precursors. The obtained atropoisomeric carbon nanodots are soluble in organic solvents and have good thermal stability, which are desirable features for technological applications. The synthetic protocol is robust, as it supports a number of variations in terms of molecular doping agents. Remarkably, the combination of axially chiral precursors and 1,4-benzoquinone as doping agent results in green-emissive carbon dots displaying circularly polarized luminescence. Dissymmetry factors of |3.5|×10-4 are obtained in solution, without the need of any additional element of chirality. Introducing axial chirality expands the strategies available to tailor the properties of carbon nanodots, paving the way for carbon nanoparticles that combine good processability in organic solvents with engineered advanced chiroptical properties.

Analysis on chronic pain management: Focus on the Italian network.

The Italian Law 38/2010, 'Dispositions to guarantee access to Palliative Care and Pain Management' orders that the health care systems of Italian regions create dedicated structures for palliative care and pain therapies, according to a specific organizational model called 'Hub-Spoke', to ensure the diagnostic-therapeutic continuity of patients affected by chronic pain (CP). The aim of our study was to investigate the Italian pain therapy network, 8 years following the approval of the Law. We sent a questionnaire to the national health representatives operating in CP management. The main result emerging from the analysis concerns the management of mini-invasive procedures, showing that 93.2% of the responding facilities carry out invasive procedures, 6.8% do not perform them and that 100% of the facilities belonging to 12 regions provided these procedures, while in eight regions more than 80%. Finally, only 38.5% of facilities declared to have a shared protocol with the relevant territorial facilities in order to guarantee the process of care and assistance of patients affected by CP. In conclusion, our study demonstrated the efficacy of the organizational model in most of the responding facilities, although the territorial management of patients after their hospital discharge should be strengthened.

A Comprehensive Review of Techniques for Processing and Analyzing Fetal Heart Rate Signals.

The availability of standardized guidelines regarding the use of electronic fetal monitoring (EFM) in clinical practice has not effectively helped to solve the main drawbacks of fetal heart rate (FHR) surveillance methodology, which still presents inter- and intra-observer variability as well as uncertainty in the classification of unreassuring or risky FHR recordings. Given the clinical relevance of the interpretation of FHR traces as well as the role of FHR as a marker of fetal wellbeing autonomous nervous system development, many different approaches for computerized processing and analysis of FHR patterns have been proposed in the literature. The objective of this review is to describe the techniques, methodologies, and algorithms proposed in this field so far, reporting their main achievements and discussing the value they brought to the scientific and clinical community. The review explores the following two main approaches to the processing and analysis of FHR signals: traditional (or linear) methodologies, namely, time and frequency domain analysis, and less conventional (or nonlinear) techniques. In this scenario, the emerging role and the opportunities offered by Artificial Intelligence tools, representing the future direction of EFM, are also discussed with a specific focus on the use of Artificial Neural Networks, whose application to the analysis of accelerations in FHR signals is also examined in a case study conducted by the authors.

A new technique for the histological diagnosis of Paget's disease of the breast using a semiautomated core needle biopsy with a 14-gauge needle.

PURPOSE: The aim of our work is to illustrate a new technique for the histological diagnosis of Paget's disease (PD) using a core needle biopsy with a semiautomated 14-gauge needle called nipple-core needle biopsy (N-CNB). We report 3 years' experience in our senology unit. MATERIALS AND METHODS: Twenty-six women with 26 clinical of nipple-areola complex (NAC) changes with suspected PD and subjected to core needle biopsy using our new 14G semiautomated needle technique were included in our study group. Institutional review board approval was obtained for this retrospective analysis. A semiautomated biopsy gun with a 14-gauge, 15-cm-long needle was used for this new procedure. After a subcutaneous injection of anesthetic and spray-ice application to the NAC, the 14G needle was opened with the cradle exposed and positioned on the NAC with considerable pressure exerted on the same. The cradle was then closed by triggering the needle spring, and 2-4 core samples were withdrawn by moving the needle position each time. Clinical, instrumental and histological differences between the lesions that gave benign results after N-CNB and those that resulted PD were analyzed by applying the Fisher's exact test. RESULTS: After N-CNB, 13/26 lesions were found to be PD (50%) while 13/26 alterations were benign (50%). No malignant lesions were detected during the follow-up in patients with benign N-CNB results. The diagnosis of PD obtained with N-CNB was confirmed in all 13 cases by means of a histological analysis of the surgical specimens. No significant post-biopsy complications were recorded. Patients with PD more frequently presented nipple retraction (ρ = 0.0407) and associated suspicious (i.e., BI-RADS 4 and 5) mammographic (ρ = 0.0006) findings compared to patients whose N-CNB had given benign results and the difference was statistically significant. CONCLUSIONS: In conclusion, with this novel technique, we were able to obtain an easy, painless, major complication-free and accurate diagnosis of PD of the NAC using a semiautomated core needle biopsy with a 14-gauge needle.

Patient-Derived Organoids as a Model for Cancer Drug Discovery.

In the search for the ideal model of tumours, the use of three-dimensional in vitro models is advancing rapidly. These are intended to mimic the in vivo properties of the tumours which affect cancer development, progression and drug sensitivity, and take into account cell-cell interactions, adhesion and invasiveness. Importantly, it is hoped that successful recapitulation of the structure and function of the tissue will predict patient response, permitting the development of personalized therapy in a timely manner applicable to the clinic. Furthermore, the use of co-culture systems will allow the role of the tumour microenvironment and tissue-tissue interactions to be taken into account and should lead to more accurate predictions of tumour development and responses to drugs. In this review, the relative merits and limitations of patient-derived organoids will be discussed compared to other in vitro and ex vivo cancer models. We will focus on their use as models for drug testing and personalized therapy and how these may be improved. Developments in technology will also be considered, including the use of microfluidics, 3D bioprinting, cryopreservation and circulating tumour cell-derived organoids. These have the potential to enhance the consistency, accessibility and availability of these models.

Spectroscopic Techniques versus Pitot Tube for the Measurement of Flow Velocity in Narrow Ducts.

In order to assess the limits and applicability of Pitot tubes for the measurement of flow velocity in narrow ducts, e.g., biomass burning plants, an optical, dual function device was implemented. This sensor, based on spectroscopic techniques, targets a trace gas, injected inside the stack either in bursts, or continuously, so performing transit time or dilution measurements. A comparison of the two optical techniques with respect to Pitot readings was carried out in different flow conditions (speed, temperature, gas composition). The results of the two optical measurements are in agreement with each other and fit quite well the theoretical simulation of the flow field, while the results of the Pitot measurements show a remarkable dependence on position and inclination of the Pitot tube with respect to the duct axis. The implications for the metrology of small combustors' emissions are outlined.

A quantitative approach for determining the role of geometrical constraints when shaping mesenchymal condensations.

In embryogenesis, mesenchymal condensation is a critical event during the formation of many organ systems, including cartilage and bone. During organ formation, mesenchymal cells aggregate and undergo compaction while activating developmental programmes. The final three-dimensional form of the organ, as well as cell fates, can be influenced by the size and shape of the forming condensation. This process is hypothesized to result from multiscale cell interactions within mesenchymal microenvironments; however, these are complex to investigate in vivo. Three-dimensional in vitro models that recapitulate key phenotypes can contribute to our understanding of the microenvironment interactions regulating this fundamental developmental process. Here we devise such models by using image analysis to guide the design of polydimethylsiloxane 3D microstructures as cell culture substrates. These microstructures establish geometrically constrained micromass cultures of mouse embryonic skeletal progenitor cells which influence the development of condensations. We first identify key phenotypes differentiating face and limb bud micromass cultures by linear discriminant analysis of the shape descriptors for condensation morphology, which are used to guide the rational design of a micropatterned polydimethylsiloxane substrate. High-content imaging analysis highlights that the geometry of the microenvironment affects the establishment and growth of condensations. Further, cells commit to establish condensations within the first 5 h; condensations reach their full size within 17 h; following which they increase cell density while maintaining size for at least 7 days. These findings elucidate the value of our model in dissecting key aspects of mesenchymal condensation development.

Preoperative loco-regional staging of invasive lobular carcinoma with contrast-enhanced digital mammography (CEDM).

The aim of our study was to assess the performance of contrast-enhanced digital mammography (CEDM) in the preoperative loco-regional staging of invasive lobular carcinoma (ILC) patients, about the valuation of the extension of disease and in measurement of lesions. Then, we selected retrospectively, among the 1500 patients underwent to CEDM at the Breast Diagnostics Department of the Careggi University Hospital of Florence and the National Cancer Institute of Milan from September 2016 to November 2018, 31 women (mean age 57.1 aa; range 41-78 aa) with a definitive histological diagnosis of ILC. CEDM has proved to be a promising imaging technique, being characterized by a sensitivity of 100% in the detection of the index lesion, and of 84.2% in identifying any adjunctive lesions: It was the presence of a non-mass enhancement (NME) to lower the sensitivity of the technique (25% vs. 100% for mass-like enhancements or a mass closely associated with a NME). Specificity in the characterization of additional lesions was 66.7%, and the diagnosis of the extension of disease was correct in 77.4% of cases: NME also led to a decrease in diagnostic accuracy in the evaluation of disease extension up to 40% versus 85% for masses and 80% for masses associated with NME (M/NME). Moreover, in 12/31 (38.7%), CEDM allowed to correctly identify lesions not shown by mammography + ultrasonography + tomosynthesis: In the half of these (6/12), there was a multicentricity, thus allowing an adequate surgical planning change. CEDM was also very accurate in analyzing the maximum diameter of the masses, while it was much less reliable in the case of the M/NME and pure NME. In conclusion, CEDM is a new promising imaging technique in the loco-regional preoperative staging and in the evaluation of disease extension for ILC, especially in case of mass enhancement lesions.