Deep Learning for hand tracking in Parkinson's Disease video-based assessment: Current and future perspectives.

BACKGROUND: Parkinson's Disease (PD) demands early diagnosis and frequent assessment of symptoms. In particular, analysing hand movements is pivotal to understand disease progression. Advancements in hand tracking using Deep Learning (DL) allow for the automatic and objective disease evaluation from video recordings of standardised motor tasks, which are the foundation of neurological examinations. In view of this scenario, this narrative review aims to describe the state of the art and the future perspective of DL frameworks for hand tracking in video-based PD assessment. METHODS: A rigorous search of PubMed, Web of Science, IEEE Explorer, and Scopus until October 2023 using primary keywords such as parkinson, hand tracking, and deep learning was performed to select eligible by focusing on video-based PD assessment through DL-driven hand tracking frameworks RESULTS:: After accurate screening, 23 publications met the selection criteria. These studies used various solutions, from well-established pose estimation frameworks, like OpenPose and MediaPipe, to custom deep architectures designed to accurately track hand and finger movements and extract relevant disease features. Estimated hand tracking data were then used to differentiate PD patients from healthy individuals, characterise symptoms such as tremors and bradykinesia, or regress the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) by automatically assessing clinical tasks such as finger tapping, hand movements, and pronation-supination. CONCLUSIONS: DL-driven hand tracking holds promise for PD assessment, offering precise, objective measurements for early diagnosis and monitoring, especially in a telemedicine scenario. However, to ensure clinical acceptance, standardisation and validation are crucial. Future research should prioritise large open datasets, rigorous validation on patients, and the investigation of new frontiers such as tracking hand-hand and hand-object interactions for daily-life tasks assessment.

Brain tumor surgery guided by navigated transcranial magnetic stimulation mapping for arithmetic calculation.

OBJECTIVE: The onco-functional balance represents the primary goal in neuro-oncology. The increasing use of navigated transcranial magnetic stimulation (nTMS) allows the noninvasive characterization of cortical functional anatomy, and its reliability for motor and language mapping has previously been validated. Calculation and arithmetic processing has not been studied with nTMS so far. In this study, the authors present their preliminary data concerning nTMS calculation. METHODS: The authors designed a monocentric prospective study, adopting an internal protocol to use nTMS for preoperative planning, including arithmetic processing. When awake surgery was possible, according to the patients' conditions, nTMS points were used to guide direct cortical stimulation (DCS), i.e., the gold standard for cortical mapping. Navigated TMS-based tractography was used for surgical planning. Statistical analyses on the nTMS and DCS points were performed. RESULTS: From February 2021 to October 2023, 61 procedures for nTMS calculation mapping were performed. The clinical evaluation, including pre- and postoperative evaluations (3 months after surgery), demonstrated a good clinical outcome with preservation of arithmetic function and recovery (92.8% of patients). Between the awake and asleep surgery groups, the postoperative clinical results were comparable at the 3-month follow-up, with > 90% of the patients achieving improved calculation function. The surgical strategy adopted was aimed at sparing nTMS positive points in asleep procedures, whereas nTMS and DCS positive points were not removed in awake procedures. Overall, 62% of the positive points for calculation functions were exposed by craniotomy and 85% were spared during surgery. None of the patients developed nTMS-related seizures. Diffusion tensor imaging fiber tracking based on nTMS positive points for calculation was used. The white matter fiber tracts involved in calculation functions were the arcuate fasciculus (56%) and frontal aslant tract (22%). When nTMS and DCS points were compared in awake surgery (n = 10 patients), a sensitivity of 31.71%, specificity of 85.76%, positive predictive value of 22.41%, negative predictive value of 90.64%, and accuracy of approximately 69% were achieved. CONCLUSIONS: Based on the authors' preliminary data, nTMS can be an advantageous tool to study cognitive functions, aimed at minimizing neurological impairment. The postoperative clinical outcome for patients who underwent operation with nTMS was very good. Considering these results, nTMS has proved to be a feasible method to map cognitive areas including those for calculation functions. Further analyses are needed to validate these data. Finally, other cognitive functions (e.g., visuospatial) may be explored with nTMS.

Genetic Causes of Qualitative Sperm Defects: A Narrative Review of Clinical Evidence.

Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in male factor infertility (MFI). However, there are still few genetic analyses that are currently recommended for use in clinical practice. In this manuscript, we reviewed the genetic causes of qualitative sperm defects. We distinguished between alterations causing reduced sperm motility (asthenozoospermia) and alterations causing changes in the typical morphology of sperm (teratozoospermia). In detail, the genetic causes of reduced sperm motility may be found in the alteration of genes associated with sperm mitochondrial DNA, mitochondrial proteins, ion transport and channels, and flagellar proteins. On the other hand, the genetic causes of changes in typical sperm morphology are related to conditions with a strong genetic basis, such as macrozoospermia, globozoospermia, and acephalic spermatozoa syndrome. We tried to distinguish alterations approved for routine clinical application from those still unsupported by adequate clinical studies. The most important aspect of the study was related to the correct identification of subjects to be tested and the correct application of genetic tests based on clear clinical data. The correct application of available genetic tests in a scenario where reduced sperm motility and changes in sperm morphology have been observed enables the delivery of a defined diagnosis and plays an important role in clinical decision-making. Finally, clarifying the genetic causes of MFI might, in future, contribute to reducing the proportion of so-called idiopathic MFI, which might indeed be defined as a subtype of MFI whose cause has not yet been revealed.

Correction: Masi et al. Stress and Workload Assessment in Aviation-A Narrative Review. Sensors 2023, 23, 3556.

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Epidemiology, surveillance and diagnosis of Usutu virus infection in the EU/EEA, 2012 to 2021.

BackgroundUsutu virus (USUV) is a flavivirus with an enzootic cycle between birds and mosquitoes; humans are incidental dead-end hosts. In Europe, the virus was first detected in Italy in 1996; since then, it has spread to many European countries.AimWe aimed to report on the epidemiology, surveillance, diagnosis and prevention of USUV infection in humans, mosquitoes and other animals in the European Union/European Economic Area (EU/EEA) from 2012 to 2021.MethodsWe collected information through a literature review, an online survey and an expert meeting.ResultsEight countries reported USUV infection in humans (105 cases, including 12 [corrected] with neurological symptoms), 15 countries in birds and seven in mosquitoes. Infected animals were also found among pets, wild and zoo animals. Usutu virus was detected primarily in Culex pipiens but also in six other mosquito species. Detection of USUV infection in humans is notifiable only in Italy, where it is under surveillance since 2017 and now integrated with surveillance in animals in a One Health approach. Several countries include USUV infection in the differential diagnosis of viral encephalitis and arbovirus infections. Animal USUV infection is not notifiable in any EU/EEA country.ConclusionHuman USUV infections, mainly asymptomatic and, less frequently, with a febrile illness or a neuroinvasive disease, have been reported in several EU/EEA countries, where the virus is endemic. Climate and environmental changes are expected to affect the epidemiology of USUV. A One Health approach could improve the monitoring of its evolution in Europe.

Stress and Workload Assessment in Aviation-A Narrative Review.

In aviation, any detail can have massive consequences. Among the potential sources of failure, human error is still the most troublesome to handle. Therefore, research concerning the management of mental workload, attention, and stress is of special interest in aviation. Recognizing conditions in which a pilot is over-challenged or cannot act lucidly could avoid serious outcomes. Furthermore, knowing in depth a pilot's neurophysiological and cognitive-behavioral responses could allow for the optimization of equipment and procedures to minimize risk and increase safety. In addition, it could translate into a general enhancement of both the physical and mental well-being of pilots, producing a healthier and more ergonomic work environment. This review brings together literature on the study of stress and workload in the specific case of pilots of both civil and military aircraft. The most common approaches for studying these phenomena in the avionic context are explored in this review, with a focus on objective methodologies (e.g., the collection and analysis of neurophysiological signals). This review aims to identify the pros, cons, and applicability of the various approaches, to enable the design of an optimal protocol for a comprehensive study of these issues.

Feasibility of Intraoperative Visual Evoked Potential Monitoring by Cortical Strip Electrodes in Patients During Brain Surgery: A Preliminary Study.

OBJECTIVE: The role of visual evoked potentials (VEPs) monitoring during neurosurgical procedure in patient remains unclear. The purpose of our study was to determine the feasibility of intraoperative VEP recording using a strip cortical electrode during surgical resection of intracranial lesions. METHODS: In this prospective, monocentric, observational study, we enrolled consecutive patients undergoing neurosurgical procedure for intracranial lesions. After dural opening, a cortical strip was positioned on the lateral occipital surface. Flash VEPs were continuously recorded using both subdermal corkscrew electrodes and strip electrodes. An electroretinogram was also recorded to guarantee delivery of adequate flash stimuli to the retina. RESULTS: We included 10 patients affected by different intracranial lesions. Flash VEPs were recorded using subdermal corkscrew electrodes in all patients except 1 in whom they were never identified during the recording. Flash VEPs were recorded using strip electrodes in all patients and showed a polyphasic morphology with a significantly larger amplitude compared with that of flash VEPs measured using subdermal corkscrew electrodes. No patient reported worsened postoperative vision and a >50% decrease in the VEPs amplitude was never registered. CONCLUSIONS: We have reported for the first time in the literature that VEP monitoring during a neurosurgical procedure is feasible via a cortical strip located on the occipital surface. The technique demonstrated greater stability and a larger amplitude compared with recordings with scalp electrodes, facilitating identification of any changes. Studies with more patients are needed to assess the clinical reliability of the technique.

Role of the membrane anchor in the regulation of Lck activity.

Theoretical work suggests that collective spatiotemporal behavior of integral membrane proteins should be modulated by boundary lipids sheathing their membrane anchors. Here, we show evidence for this prediction while investigating the mechanism for maintaining a steady amount of the active form of integral membrane protein Lck kinase (LckA) by Lck trans-autophosphorylation regulated by the phosphatase CD45. We used super-resolution microscopy, flow cytometry, and pharmacological and genetic perturbation to gain insight into the spatiotemporal context of this process. We found that LckA is generated exclusively at the plasma membrane, where CD45 maintains it in a ceaseless dynamic equilibrium with its unphosphorylated precursor. Steady LckA shows linear dependence, after an initial threshold, over a considerable range of Lck expression levels. This behavior fits a phenomenological model of trans-autophosphorylation that becomes more efficient with increasing LckA. We then challenged steady LckA formation by genetically swapping the Lck membrane anchor with structurally divergent ones, such as that of Src or the transmembrane domains of LAT, CD4, palmitoylation-defective CD4 and CD45 that were expected to drastically modify Lck boundary lipids. We observed small but significant changes in LckA generation, except for the CD45 transmembrane domain that drastically reduced LckA due to its excessive lateral proximity to CD45. Comprehensively, LckA formation and maintenance can be best explained by lipid bilayer critical density fluctuations rather than liquid-ordered phase-separated nanodomains, as previously thought, with "like/unlike" boundary lipids driving dynamical proximity and remoteness of Lck with itself and with CD45.

Assessment Tasks and Virtual Exergames for Remote Monitoring of Parkinson's Disease: An Integrated Approach Based on Azure Kinect.

Motor impairments are among the most relevant, evident, and disabling symptoms of Parkinson's disease that adversely affect quality of life, resulting in limited autonomy, independence, and safety. Recent studies have demonstrated the benefits of physiotherapy and rehabilitation programs specifically targeted to the needs of Parkinsonian patients in supporting drug treatments and improving motor control and coordination. However, due to the expected increase in patients in the coming years, traditional rehabilitation pathways in healthcare facilities could become unsustainable. Consequently, new strategies are needed, in which technologies play a key role in enabling more frequent, comprehensive, and out-of-hospital follow-up. The paper proposes a vision-based solution using the new Azure Kinect DK sensor to implement an integrated approach for remote assessment, monitoring, and rehabilitation of Parkinsonian patients, exploiting non-invasive 3D tracking of body movements to objectively and automatically characterize both standard evaluative motor tasks and virtual exergames. An experimental test involving 20 parkinsonian subjects and 15 healthy controls was organized. Preliminary results show the system's ability to quantify specific and statistically significant (p < 0.05) features of motor performance, easily monitor changes as the disease progresses over time, and at the same time permit the use of exergames in virtual reality both for training and as a support for motor condition assessment (for example, detecting an average reduction in arm swing asymmetry of about 14% after arm training). The main innovation relies precisely on the integration of evaluative and rehabilitative aspects, which could be used as a closed loop to design new protocols for remote management of patients tailored to their actual conditions.

Evaluation of Arm Swing Features and Asymmetry during Gait in Parkinson's Disease Using the Azure Kinect Sensor.

Arm swinging is a typical feature of human walking: Continuous and rhythmic movement of the upper limbs is important to ensure postural stability and walking efficiency. However, several factors can interfere with arm swings, making walking more risky and unstable: These include aging, neurological diseases, hemiplegia, and other comorbidities that affect motor control and coordination. Objective assessment of arm swings during walking could play a role in preventing adverse consequences, allowing appropriate treatments and rehabilitation protocols to be activated for recovery and improvement. This paper presents a system for gait analysis based on Microsoft Azure Kinect DK sensor and its body-tracking algorithm: It allows noninvasive full-body tracking, thus enabling simultaneous analysis of different aspects of walking, including arm swing characteristics. Sixteen subjects with Parkinson's disease and 13 healthy controls were recruited with the aim of evaluating differences in arm swing features and correlating them with traditional gait parameters. Preliminary results show significant differences between the two groups and a strong correlation between the parameters. The study thus highlights the ability of the proposed system to quantify arm swing features, thus offering a simple tool to provide a more comprehensive gait assessment.

Validation of a Novel Three-Dimensional (3D Fusion) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study.

We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3-G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion (p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods (p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.

Allosteric activation of T cell antigen receptor signaling by quaternary structure relaxation.

The mechanism of T cell antigen receptor (TCR-CD3) signaling remains elusive. Here, we identify mutations in the transmembrane region of TCRß or CD3ζ that augment peptide T cell antigen receptor (pMHC)-induced signaling not explicable by enhanced ligand binding, lateral diffusion, clustering, or co-receptor function. Using a biochemical assay and molecular dynamics simulation, we demonstrate that the gain-of-function mutations loosen the interaction between TCRαß and CD3ζ. Similar to the activating mutations, pMHC binding reduces TCRαß cohesion with CD3ζ. This event occurs prior to CD3ζ phosphorylation and at 0°C. Moreover, we demonstrate that soluble monovalent pMHC alone induces signaling and reduces TCRαß cohesion with CD3ζ in membrane-bound or solubilised TCR-CD3. Our data provide compelling evidence that pMHC binding suffices to activate allosteric changes propagating from TCRαß to the CD3 subunits, reconfiguring interchain transmembrane region interactions. These dynamic modifications could change the arrangement of TCR-CD3 boundary lipids to license CD3ζ phosphorylation and initiate signal propagation.

Electrodiagnostic findings in patients with non-COVID-19- and COVID-19-related acute respiratory distress syndrome.

BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) is a frequent neurological manifestation in patients with acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19) infection. CIPNM diagnosis is usually limited to clinical evaluation. We compared patients with ARDS from COVID-19 and other aetiologies, in whom a neurophysiological evaluation for the detection of CIPNM was performed. The aim was to determine if there were any differences between these two groups in frequency of CINPM and outcome at discharge from the intensive care unit (ICU). MATERIALS AND METHODS: This was a single-centre retrospective study performed on mechanically ventilated patients consecutively admitted (January 2016-June 2020) to the ICU of Careggi Hospital, Florence, Italy, with ARDS of different aetiologies. Neurophysiological evaluation was performed on patients with stable ventilation parameters, but marked widespread hyposthenia (Medical Research Council score <48). Creatine phosphokinase (CPK), lactic dehydrogenase (LDH) and mean morning glycaemic values were collected. RESULTS: From a total of 148 patients, 23 with COVID-19 infection and 21 with ARDS due to other aetiologies, underwent electroneurography/electromyography (ENG/EMG) recording. Incidence of CIPNM was similar in the two groups, 65% (15 of 23) in COVID-19 patients and 71% (15 of 21) in patients affected by ARDS of other aetiologies. At ICU discharge, subjects with CIPNM more frequently required ventilatory support, regardless the aetiology of ARDS. CONCLUSION: ENG/EMG represents a useful tool in the identification of the neuromuscular causes underlying ventilator wean failure and patient stratification. A high incidence of CIPNM, with a similar percentage, has been observed in ARDS patients of all aetiologies.

Improving the Corrosion Resistance of Wrought ZM21 Magnesium Alloys by Plasma Electrolytic Oxidation and Powder Coating.

Plasma Electrolytic Oxidation (PEO) was applied to extruded ZM21 Mg alloys to improve their corrosion resistance in a chloride-containing environment. PEO was carried out in DC mode and voltage control in a fluoride-free electrolyte. Potentiodynamic polarization tests in 3.5 wt.% NaCl aqueous solution and neutral salt spray (NSS) tests were carried out. Microstructural and profilometric characterization, as well as NSS tests were performed in different conditions: (i) bare ZM21, (ii) PEO-treated ZM21, (iii) powder-coated ZM21 (without PEO interlayer), and (iv) PEO-treated ZM21 with powder coating top layer (carboxyl-functionalized polyester resin). The PEO + powder coating double layer was identified as the best-performing corrosion protection.

Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo'.

On 21 February 2020, a resident of the municipality of Vo', a small town near Padua (Italy), died of pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection1. This was the first coronavirus disease 19 (COVID-19)-related death detected in Italy since the detection of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province2. In response, the regional authorities imposed the lockdown of the whole municipality for 14 days3. Here we collected information on the demography, clinical presentation, hospitalization, contact network and the presence of SARS-CoV-2 infection in nasopharyngeal swabs for 85.9% and 71.5% of the population of Vo' at two consecutive time points. From the first survey, which was conducted around the time the town lockdown started, we found a prevalence of infection of 2.6% (95% confidence interval (CI): 2.1-3.3%). From the second survey, which was conducted at the end of the lockdown, we found a prevalence of 1.2% (95% CI: 0.8-1.8%). Notably, 42.5% (95% CI: 31.5-54.6%) of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic (that is, did not have symptoms at the time of swab testing and did not develop symptoms afterwards). The mean serial interval was 7.2 days (95% CI: 5.9-9.6). We found no statistically significant difference in the viral load of symptomatic versus asymptomatic infections (P = 0.62 and 0.74 for E and RdRp genes, respectively, exact Wilcoxon-Mann-Whitney test). This study sheds light on the frequency of asymptomatic SARS-CoV-2 infection, their infectivity (as measured by the viral load) and provides insights into its transmission dynamics and the efficacy of the implemented control measures.

Genome editing technologies to treat rare liver diseases.

Liver has a central role in protein and lipid metabolism, and diseases involving hepatocytes have often repercussions on multiple organs and systems. Hepatic disorders are frequently characterized by production of defective or non-functional proteins, and traditional gene therapy approaches have been attempted for years to restore adequate protein levels through delivery of transgenes. Recently, many different genome editing platforms have been developed aimed at correcting at DNA level the defects underlying the diseases. In this Review we discuss the latest applications of these tools applied to develop therapeutic strategies for rare liver disorders, in particular updating the literature with the most recent strategies relying on base editors technology.

Long-Term Outcomes of Parathyroidectomy in Hyperparathyroidism-Jaw Tumor Syndrome: Analysis of Five Families with CDC73 Mutations.

BACKGROUND: Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare disease caused by CDC73 germline mutations, with familial primary hyperparathyroidism (pHPT), ossifying jaw tumors, genito-urinary neoplasms. The present study was aimed at determining the long-term postoperative outcome of parathyroidectomy in HPT-JT. METHODS: A retrospective analysis of a single-center series of 20 patients from five unrelated HPT-JT families undergoing parathyroid surgery was performed. RESULTS: Pathology confirmed a single-gland involvement in 95% of cases at onset. Parathyroid carcinoma occurred in three patients undergoing en-bloc parathyroidectomy and thyroid lobectomy: parathyroid benign lesions in 17 patients undergoing subtotal parathyroidectomy for evident multiglandular involvement (n = 1) or selective parathyroidectomy for single-gland involvement (n = 16), during bilateral (n = 13) or targeted unilateral neck exploration (n = 7). At a median overall follow-up of 16 years (range 2.5-42), patients with parathyroid carcinoma had a persistent/recurrent disease in 66.6%; patients with benign lesions had recurrent pHPT in 23.5% after a prolonged disease-free period; recurrent benign pHPT occurred slightly more often in cases of discordant preoperative localization (60% vs 9%; p = 0.06). CONCLUSION: pHPT in HPT-JT is generally characterized by a benign and single-gland involvement, with a relatively increased risk of malignancy (15%). Parathyroid carcinoma needs extensive surgery because of high risk of permanent/recurrent disease (66.6%). In benign involvement, targeted unilateral exploration with selective parathyroidectomy may be effective in cases of concordant single-gland localization at preoperative localization imaging techniques. Bilateral neck exploration with subtotal parathyroidectomy might be preferred in cases of negative or discordant preoperative localization, because of the increased risk of multiglandular involvement and long-term recurrences (23.5%).

Modelling Neurotropic Flavivirus Infection in Human Induced Pluripotent Stem Cell-Derived Systems.

Generation of human induced pluripotent stem cells (hiPSCs) and their differentiation into a variety of cells and organoids have allowed setting up versatile, non-invasive, ethically sustainable, and patient-specific models for the investigation of the mechanisms of human diseases, including viral infections and host-pathogen interactions. In this study, we investigated and compared the infectivity and replication kinetics in hiPSCs, hiPSC-derived neural stem cells (NSCs) and undifferentiated neurons, and the effect of viral infection on host innate antiviral responses of representative flaviviruses associated with diverse neurological diseases, i.e., Zika virus (ZIKV), West Nile virus (WNV), and dengue virus (DENV). In addition, we exploited hiPSCs to model ZIKV infection in the embryo and during neurogenesis. The results of this study confirmed the tropism of ZIKV for NSCs, but showed that WNV replicated in these cells with much higher efficiency than ZIKV and DENV, inducing massive cell death. Although with lower efficiency, all flaviviruses could also infect pluripotent stem cells and neurons, inducing similar patterns of antiviral innate immune response gene expression. While showing the usefulness of hiPSC-based infection models, these findings suggest that additional virus-specific mechanisms, beyond neural tropism, are responsible for the peculiarities of disease phenotype in humans.