Search

Abstract Neurological disorders, such as Parkinson’s disease (PD), multiple sclerosis (MS), cerebral palsy (CP) and stroke are well-known causes of gait and balance alterations. Innovative devices (i.e., robotics) are often used to promote motor recovery. As an alternative, anti-gravity treadmills, which were developed by NASA, allow early mobilization, walking with less effort to reduce gait energy costs and fatigue. A systematic search, according to PRISMA guidelines, was conducted for all peer-reviewed articles published from January 2010 through September 2023, using the following databases: PubMed, Scopus, PEDro and IEEE Xplore. After an accurate screening, we selected only 16 articles (e.g., 5 RCTs, 2 clinical trials, 7 pilot studies, 1 prospective study and 1 exploratory study). The evidence collected in this systematic review reported promising results in the field of anti-gravity technology for neurological patients, in terms of improvement in gait and balance outcomes. However, we are not able to provide any clinical recommendation about the dose and parameters of anti-gravity treadmill training, because of the lack of robust high-quality RCT studies and large samples. Registration number CRD42023459665.

Abstract Algal biomass is a viable source of chemicals and metabolites for various energy, nutritional, medicinal and agricultural uses. While stresses have commonly been used to induce metabolite accumulation in microalgae in attempts to enhance high-value product yields, this is often very detrimental to growth. Therefore, understanding how to modify metabolism without deleterious consequences is highly beneficial. We demonstrate that low-doses (1–5 Gy) of ionizing radiation in the X-ray range induces a non-toxic, hormetic response in microalgae to promote metabolic activation. We identify specific radiation exposure parameters that give reproducible metabolic responses in Chlorella sorokiniana caused by transcriptional changes. This includes up-regulation of >30 lipid metabolism genes, such as genes encoding an acetyl-CoA carboxylase subunit, phosphatidic acid phosphatase, lysophosphatidic acid acyltransferase, and diacylglycerol acyltransferase. The outcome is an increased lipid yield in stationary phase cultures by 25% in just 24 hours, without any negative effects on cell viability or biomass.

Abstract No prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBIT (NCT02631447) was a randomized, three-arm, noncomparative phase II trial in which patients were randomized to one of two sequences with immunotherapy or targeted therapy first, with a third arm in which an 8-week induction course of targeted therapy followed by a planned switch to immunotherapy was the first treatment. BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. Primary outcome of overall survival was previously reported, demonstrating improved survival with immunotherapy administered until progression and followed by BRAF/MEK inhibition. Here we report 4-year survival outcomes, confirming long-term benefit with first-line immunotherapy. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy.

Lower limb exoskeletons represent a relevant tool for rehabilitating gait in patients with lower limb movement disorders. Partial assistance exoskeletons adaptively provide the joint torque needed, on top of that produced by the patient, for a correct and stable gait, helping the patient to recover an autonomous gait. Thus, the device needs to identify the different phases of the gait cycle to produce precisely timed commands that drive its joint motors appropriately. In this study, EMG signals have been used for gait phase detection considering that EMG activations lead limb kinematics by at least 120 ms. We propose a deep learning model based on bidirectional LSTM to identify stance and swing gait phases from EMG data. We built a dataset of EMG signals recorded at 1500 Hz from four muscles from the dominant leg in a population of 26 healthy subjects walking overground (WO) and walking on a treadmill (WT) using a lower limb exoskeleton. The data were labeled with the corresponding stance or swing gait phase based on limb kinematics provided by inertial motion sensors. The model was studied in three different scenarios, and we explored its generalization abilities and evaluated its applicability to the online processing of EMG data. The training was always conducted on 500-sample sequences from WO recordings of 23 subjects. Testing always involved WO and WT sequences from the remaining three subjects. First, the model was trained and tested on 500 Hz EMG data, obtaining an overall accuracy on the WO and WT test datasets of 92.43% and 91.16%, respectively. The simulation of online operation required 127 ms to preprocess and classify one sequence. Second, the trained model was evaluated against a test set built on 1500 Hz EMG data. The accuracies were lower, yet the processing times were 11 ms faster. Third, we partially retrained the model on a subset of the 1500 Hz training dataset, achieving 87.17% and 89.64% accuracy on the 1500 Hz WO and WT test sets, respectively. Overall, the proposed deep learning model appears to be a valuable candidate for entering the control pipeline of a lower limb rehabilitation exoskeleton in terms of both the achieved accuracy and processing times.

As instituições do sistema financeiro brasileiro são pressionadas, por parte dos investidores, a aumentarem a eficiência operacional. Essas instituições tornam-se dependentes de plataformas tecnológicas, que precisam estar disponíveis, pois o risco operacional decorrente de indisponibilidades potencializa perdas financeiras significativas. A criação de uma gestão de continuidade de negócios eficaz permite a execução de um plano de resposta a eventos de alto impacto, indicando métodos, métricas e ferramentas para momentos de crise. Assim, este estudo tem como objetivo analisar a capacidade das empresas do setor financeiro para responderem a eventos de crises e de total parada em suas operações, atendendo aos requisitos específicos da NBR ISO/IEC 22301. Neste estudo de casos múltiplos, propomos uma coleta de informações, com entrevistas semiestruturadas, junto a uma amostra de cinco instituições do segmento financeiro, localizadas em Brasília e São Paulo e que aplicam frameworks de boas práticas de gestão de negócios e governança corporativa.

CDK4/6 inhibitors have revolutionized the treatment algorithm of luminal metastatic breast cancer, becoming the recommended first-line therapy in association with endocrine therapy. However, due to its theoretically greater and more rapid tumor shrinkage, the upfront use of chemotherapy is considered in some clinical situations like visceral crisis. At the state of the art level, a paucity of data is available about the use of CDK4/6 inhibitors in patients presenting with visceral crisis or with life-threatening conditions since this population was historically excluded from clinical trials. In addition, data regarding direct comparison between combinations of chemotherapy and CDK4/6 inhibitors in terms of efficacy, rapidity of responses and long-term outcomes are lacking. We report the case of a 68-year-old woman with luminal metastatic breast cancer presenting at diagnosis with a critical and potentially life-threatening condition. The patient was treated with first-line Abemaciclib plus letrozole and achieved a rapid partial response with sudden clinical stabilization. Although the patient did not technically present with a visceral crisis, this case presentation also endorsed the upfront use of CDK4/6 inhibitor combinations in critical clinical situations in the absence of severe organ dysfunction and after multidisciplinary discussion.

Purpose: To assess the diagnostic accuracy of traditional chest X-ray (CXR) and digital tomosynthesis (DTS) compared to computed tomography (CT) in detecting pulmonary interstitial changes in patients having recovered from severe COVID-19. Materials and Methods: This was a retrospective observational study, and received local ethics committee approval. Patients suspected of having COVID-19 pneumonia upon emergency department admission between 1 March and 31 August 2020, and who underwent CXR followed by DTS and CT, were considered. Inclusion criteria were as follows: (1) patients with previous SARS-CoV-2 infection proven by a positive RT-PCR on nasopharyngeal swabs performed upon admission to the hospital, and with complete clinical recovery; (2) a diagnosis of SARS-CoV-2-related ARDS, according to the Berlin criteria, during hospitalization; (3) no recent history of other lung disease; and (4) complete imaging follow-up by CXR, DTS, and CT for at least 6 months and up to one year. Analysis of DTS images was carried out independently by two radiologists with 16 and 10 years of experience in chest imaging, respectively. The following findings were evaluated: (1) ground-glass opacities (GGOs); (2) air-space consolidations with or without air bronchogram; (3) reticulations; and (4) linear consolidation. Indicators of diagnostic performance of RX and digital tomosynthesis were calculated using CT as a reference. All data were analyzed using R statistical software (version 4.0.2, 2020). Results: Out of 44 patients initially included, 25 patients (17 M/8 F), with a mean age of 64 years (standard deviation (SD): 12), met the criteria and were included. The overall average numbers of findings confirmed by CT were GGOs in 11 patients, lung consolidations in 8 patients, 7 lung interstitial reticulations, and linear consolidation in 20 patients. DTS showed a significantly higher diagnostic accuracy compared to CXR in recognizing interstitial lung abnormalities—especially GGOs (p = 0.0412) and linear consolidations (p = 0.0009). The average dose for chest X-ray was 0.10 mSv (0.07–0.32), for DTS was 1.03 mSv (0.74–2.00), and for CT scan was 3 mSv. Conclusions: According to our results, DTS possesses a high diagnostic accuracy, compared with CXR, in revealing lung fibrotic changes in patients who have recovered from COVID-19 pneumonia.

Abstract Background To evaluate the capability of basal and one-month differed white blood cells (WBC), neutrophil, lymphocyte and platelet values and their ratios (neutrophils-to-lymphocytes ratio, NLR, and platelets-to-lymphocytes ratio, PLR) in predicting the response to immune checkpoint inhibitors (ICI) in metastatic melanoma (MM). Methods We performed a retrospective study of 272 BRAF wild-type MM patients treated with first line ICI. Bivariable analysis was used to correlate patient/tumor characteristics with clinical outcomes. Variations between time 1 and time 0 (Δ) of blood parameters were also calculated and dichotomized using cut-off values assessed by ROC curve. Results At baseline, higher neutrophils and NLR negatively correlated with PFS, OS and disease control rate (DCR). Higher PLR was also associated with worse OS. In multivariable analysis, neutrophils (p = 0.003), WBC (p = 0.069) and LDH (p = 0.07) maintained their impact on PFS, while OS was affected by LDH (p

Lower limb exoskeletons represent a relevant tool for rehabilitating gait in patients with lower limb movement disorders. Partial assistance exoskeletons adaptively provide the joint torque needed, on top of that produced by the patient, for a correct and stable gait, helping the patient to recover an autonomous gait. Thus, the device needs to identify the different phases of the gait cycle to produce precisely timed commands that drive its joint motors appropriately. In this study, EMG signals have been used for gait phase detection considering that EMG activations lead limb kinematics by at least 120 ms. We propose a deep learning model based on bidirectional LSTM to identify stance and swing gait phases from EMG data. We built a dataset of EMG signals recorded at 1500 Hz from four muscles from the dominant leg in a population of 26 healthy subjects walking overground (WO) and walking on a treadmill (WT) using a lower limb exoskeleton. The data were labeled with the corresponding stance or swing gait phase based on limb kinematics provided by inertial motion sensors. The model was studied in three different scenarios, and we explored its generalization abilities and evaluated its applicability to the online processing of EMG data. The training was always conducted on 500-sample sequences from WO recordings of 23 subjects. Testing always involved WO and WT sequences from the remaining three subjects. First, the model was trained and tested on 500 Hz EMG data, obtaining an overall accuracy on the WO and WT test datasets of 92.43% and 91.16%, respectively. The simulation of online operation required 127 ms to preprocess and classify one sequence. Second, the trained model was evaluated against a test set built on 1500 Hz EMG data. The accuracies were lower, yet the processing times were 11 ms faster. Third, we partially retrained the model on a subset of the 1500 Hz training dataset, achieving 87.17% and 89.64% accuracy on the 1500 Hz WO and WT test sets, respectively. Overall, the proposed deep learning model appears to be a valuable candidate for entering the control pipeline of a lower limb rehabilitation exoskeleton in terms of both the achieved accuracy and processing times. [ABSTRACT FROM AUTHOR]

Critically ill patients admitted to the intensive care unit require continuous monitoring of vital functions as well as mechanical and pharmacological support, provided through different devices. Chest radiographs play a fundamental role in monitoring the conditions of these patients and assessing the intensive-care devices after their insertion; therefore, the radiologist needs to know their normal appearance and their correct position and should be aware of the possible complications that may occur after their placement. This pictorial review illustrates the radiographic appearance of non-cardiological devices commonly used in clinical practice (central venous catheters, tunneled catheters, Swan-Ganz catheters, chest tubes, endotracheal tubes, and nasogastric tubes), their correct position and the most common complications that may occur after their placement.

When brain damage occurs, gait and balance are often impaired. Evaluation of the gait cycle, therefore, has a pivotal role during the rehabilitation path of subjects who suffer from neurological disorders. Gait analysis can be performed through laboratory systems, non-wearable sensors (NWS), and/or wearable sensors (WS). Using these tools, physiotherapists and neurologists have more objective measures of motion function and can plan tailored and specific gait and balance training early to achieve better outcomes and improve patients’ quality of life. However, most of these innovative tools are used for research purposes (especially the laboratory systems and NWS), although they deserve more attention in the rehabilitation field, considering their potential in improving clinical practice. In this narrative review, we aimed to summarize the most used gait analysis systems in neurological patients, shedding some light on their clinical value and implications for neurorehabilitation practice.

Background: Endocrine therapy (ET) plus cyclin-dependent-kinases 4/6 inhibitors (CDK4/6i) represents the standard treatment for luminal-metastatic breast cancer (MBC). However, prospective head-to-head comparisons are still lacking for 1st line (L) options, and it is still crucial to define the best strategy between 1st and 2nd L. Materials and methods: 717 consecutive luminal-MBC pts treated between 2008 and 2020 were analyzed at the Oncology Department of Aviano and Udine, Italy. Differences about survival outcomes (OS, PFS and PPS) were tested by log-rank test. The attrition rate (AR) between 1st and 2ndL was calculated. Results: At 1stL, pts were treated with ET (49%), chemotherapy (CT) (31%) and ET-CDKi (20%) while, at 2ndL, 33% received ET, 33% CT and 8% ET-CDKi. Overall AR was 10%, 7% for CT, 8% for ET and 17% for ET-CDKi. By multivariate analysis, 1stL ET-CDK4/6i showed a better mPFS1 and OS. Moreover, 2ndL ET-CDK4/6i demonstrated better mPFS2 compared to ET and CT. Notably, 1stL ET-CDKi resulted in higher mPFS than 2ndL ET-CDKi. Intriguingly, 1stL ET-CDK4/6i was associated with worse mPPS compared to CT and ET. Secondarily, 1stL ET-CDK4/6i followed by CT had worse OS compared to 1stL ET-CDK4/6i followed by ET. Notably, none of baseline characteristics at 2ndL influenced 2ndL treatment choice (ET vs. CT) after ET-CDKi. Conclusion: Our real-world data demonstrated that ET-CDKi represents the best option for 1stL luminal-MBC compared to ET and CT. Also, the present study pointed out that 2ndL ET, potentially combined with other molecules, could be a feasible option after CDK4/6i failure, postponing CT on later lines.

BackgroundA multidisciplinary team meeting (MDM) approach in breast cancer (BC) management is a standard of care. One of the roles of MDMs is to identify the best diagnostic and therapeutic strategies for patients (pts) with new diagnosis of early BC. The purpose of this study was to define whether there was an agreement between the planned program (i.e., MDMs-based decision) and that actually applied. In addition, the study explored factors associated with discordance.MethodsWe conducted a retrospective study of a consecutive series of 291 patients with new diagnosis of early BC, discussed at MDMs at the University Hospital of Udine (Italy), from January 2017 to June 2018. The association between clinico-biological factors and discordance between what was decided during the MDMs and what was consequently applied by the oncologist was explored through uni- and multivariate logistic regression analyses.ResultsThe median age was 62 years (range 27–88 years). Among invasive early BC patients, the most frequent phenotype was luminal A (38%), followed by luminal B (33%), HER2-positive (12%), and triple-negative (5%). In situ carcinoma (DCIS) represented 12% of cases. The median time from MDM discussion to first oncologic examination was 2 weeks. The rate of discordance between MDM-based decision and final choice, during a face-to-face consultation with the oncologist, was 15.8% (46/291). The most frequent reason for changing the MDM-based program was clinical decision (87%). Follow-up was preferred to the chemotherapy (CT) proposed within the MDMs in 15% of cases, and to the endocrine therapy (ET) in 39% of cases (among these, 44.5% had a diagnosis of DCIS). Therapeutic change from sequential CT-ET to ET alone was chosen in 16/46 pts (35%): among these patients, seven had a luminal B disease and six had an HER2-positive disease. On univariate analysis, factors associated with discordance were values of Ki-67 14%–30% (OR 3.91; 95% CI 1.19–12.9), age >70 years (OR 2.44, 95% CI 1.28–4.63), housewife/retired status (OR 2.35, 95% CI 1.14–4.85), polypharmacy (OR 1.95; 95% CI 1.02–3.72), postmenopausal status (OR 4.15; 95% CI 1.58–10.9), and high Charlson Comorbidity Index (OR 1.31; 95% CI 1.09–1.57). The association with marital status, educational level, alcohol and smoke habits, presence of a caregiver, parity, grading, histotype and phenotype, and stage was not statistically significant. On multivariate analysis, only Ki-67 value maintained its statistical significance.ConclusionThe results of our study could be useful for enhancing the role of MDMs in the clinical decision-making process in early BC.

Abstract The inter-session Intraclass Correlation Coefficient (ICC) is a commonly investigated and clinically important metric of reliability for pressure pain threshold (PPT) measurement. However, current investigations do not account for inter-repetition variability when calculating inter-session ICC, even though a PPT measurement taken at different sessions must also imply different repetitions. The primary aim was to evaluate and report a novel metric of reliability in PPT measurement: the inter-session-repetition ICC. One rater recorded ten repetitions of PPT measurement over the lumbar region bilaterally at two sessions in twenty healthy adults using a pressure algometer. Variance components were computed using linear mixed-models and used to construct ICCs; most notably inter-session ICC and inter-session-repetition ICC. At 70.1% of the total variance, the source of greatest variability was between subjects ( $${\sigma }_{subj}^{2}$$ σ subj 2 = 222.28 N2), whereas the source of least variability (1.5% total variance) was between sessions ( $${\sigma }_{sess}^{2}$$ σ sess 2 = 4.83 N2). Derived inter-session and inter-session-repetition ICCs were 0.88 (95%CI: 0.77 to 0.94) and 0.73 (95%CI: 0.53 to 0.84) respectively. Inter-session-repetition ICC provides a more conservative estimate of reliability than inter-session ICC, with the magnitude of difference being clinically meaningful. Quantifying individual sources of variability enables ICC construction to be reflective of individual testing protocols.

Simple Summary: Our study demonstrated neural encoding of incidental sensory regularities leading to modulation of cortical responses to both predictive and predicted sensory stimuli. As in the case of goal-directed behavior, such task-irrelevant predictive mechanisms might result from the brain's intrinsic drive of reducing uncertainty about state transition dynamics of the environment. Statistical learning of sensory patterns can lead to predictive neural processes enhancing stimulus perception and enabling fast deviancy detection. Predictive processes have been extensively demonstrated when environmental statistical regularities are relevant to task execution. Preliminary evidence indicates that statistical learning can even occur independently of task relevance and top-down attention, although the temporal profile and neural mechanisms underlying sensory predictions and error signals induced by statistical learning of incidental sensory regularities remain unclear. In our study, we adopted an implicit sensory conditioning paradigm that elicited the generation of specific perceptual priors in relation to task-irrelevant audio–visual associations, while recording Electroencephalography (EEG). Our results showed that learning task-irrelevant associations between audio–visual stimuli resulted in anticipatory neural responses to predictive auditory stimuli conveying anticipatory signals of expected visual stimulus presence or absence. Moreover, we observed specific modulation of cortical responses to probabilistic visual stimulus presentation or omission. Pattern similarity analysis indicated that predictive auditory stimuli tended to resemble the response to expected visual stimulus presence or absence. Remarkably, Hierarchical Gaussian filter modeling estimating dynamic changes of prediction error signals in relation to differential probabilistic occurrences of audio–visual stimuli further demonstrated instantiation of predictive neural signals by showing distinct neural processing of prediction error in relation to violation of expected visual stimulus presence or absence. Overall, our findings indicated that statistical learning of non-salient and task-irrelevant perceptual regularities could induce the generation of neural priors at the time of predictive stimulus presentation, possibly conveying sensory-specific information about the predicted consecutive stimulus. [ABSTRACT FROM AUTHOR]

This study investigates whether a not informative, irrelevant emotional reaction of disgust interferes with decision-making under uncertainty. We manipulate the Iowa Gambling Task (IGT) by associating a disgust-eliciting image with selections from Disadvantageous/Bad decks (Congruent condition) or Advantageous/Good decks (Incongruent condition). A Control condition without manipulations is also included. Results indicate an increased probability of selecting from a Good deck as the task unfolds in all conditions. However, this effect is modulated by the experimental manipulation. Specifically, we detect a detrimental effect (i.e., a significant decrease in the intercept) of the disgust-eliciting image in Incongruent condition (vs. Control), but this effect is limited to the early stages of the task (i.e., first twenty trials). No differences in performance trends are detected between Congruent and Control conditions. Anticipatory Skin Conductance Response, heart rate, and pupil dilation are also assessed as indexes of anticipatory autonomic activation following the Somatic Marker Hypothesis, but no effects are shown for the first two indexes in any of the conditions. Only a decreasing trend is detected for pupil dilation as the task unfolds in Control and Incongruent conditions. Results are discussed in line with the "risk as feelings" framework, the Somatic Marker Hypothesis, and IGT literature. [ABSTRACT FROM AUTHOR]