Circulating biomarkers as predictors of response to immune checkpoint inhibitors in NSCLC: Are we on the right path?

Immune checkpoints inhibitors (ICIs) have markedly improved the therapeutic management of advanced NSCLC and, more recently, they have demonstrated efficacy also in the early-stage disease. Despite better survival outcomes with ICIs compared to standard chemotherapy, a large proportion of patients can derive limited clinical benefit from these agents. So far, few predictive biomarkers, including the programmed death-ligand 1 (PD-L1), have been introduced in clinical practice. Therefore, there is an urgent need to identify novel biomarkers to select patients for immunotherapy, to improve efficacy and avoid unnecessary toxicity. A deeper understanding of the mechanisms involved in antitumor immunity and advances in the field of liquid biopsy have led to the identification of a wide range of circulating biomarkers that could potentially predict response to immunotherapy. Herein, we provide an updated overview of these circulating biomarkers, focusing on emerging data from clinical studies and describing modern technologies used for their detection.

Electrocortical correlates of attention differentiate individual capacity in associative learning.

Associative learning abilities vary considerably among individuals, with attentional processes suggested to play a role in these variations. However, the relationship between attentional processes and individual differences in associative learning remains unclear, and whether these variations reflect in event-related potentials (ERPs) is unknown. This study aimed to investigate the relationship between attentional processes and associative learning by recording electrocortical activity of 38 young adults (18-32 years) during an associative learning task. Learning performance was assessed using the signal detection index d'. EEG topographic analyses and source localizations were applied to examine the neural correlates of attention and associative learning. Results revealed that better learning scores are associated with (1) topographic differences during early (126-148 ms) processing of the stimulus, coinciding with a P1 ERP component, which corresponded to a participation of the precuneus (BA 7), (2) topographic differences at 573-638 ms, overlapping with an increase of global field power at 530-600 ms, coinciding with a P3b ERP component and localized within the superior frontal gyrus (BA11) and (3) an increase of global field power at 322-507 ms, underlay by a stronger participation of the middle occipital gyrus (BA 19). These insights into the neural mechanisms underlying individual differences in associative learning suggest that better learners engage attentional processes more efficiently than weaker learners, making more resources available and displaying increased functional activity in areas involved in early attentional processes (BA7) and decision-making processes (BA11) during an associative learning task. This highlights the crucial role of attentional mechanisms in individual learning variability.

Interindividual variations in associative visual learning: Exploration, description, and partition of response characteristics.

Relying on existing literature to identify suitable techniques for characterizing individual differences presents practical and methodological challenges. These challenges include the frequent absence of detailed descriptions of raw data, which hinders the assessment of analysis appropriateness, as well as the exclusion of data points deemed outliers, or the reliance on comparing only extreme groups by categorizing continuous variables into upper and lower quartiles. Despite the availability of algorithmic modeling in standard statistical software, investigations into individual differences predominantly focus on factor analysis and parametric tests. To address these limitations, this application-oriented study proposes a comprehensive approach that leverages behavioral responses through the use of signal detection theory and clustering techniques. Unlike conventional methods, signal detection theory considers both sensitivity and bias, offering insights into the intricate interplay between perceptual ability and decision-making processes. On the other hand, clustering techniques enable the identification and classification of distinct patterns within the dataset, allowing for the detection of singular behaviors that form the foundation of individual differences. In a broader framework, these combined approaches prove particularly advantageous when analyzing large and heterogeneous datasets provided by data archive platforms. By applying these techniques more widely, our understanding of the cognitive and behavioral processes underlying learning can be expedited and enhanced.

Dynamic rewiring of electrophysiological brain networks during learning.

Human learning is an active and complex process. However, the brain mechanisms underlying human skill learning and the effect of learning on the communication between brain regions, at different frequency bands, are still largely unknown. Here, we tracked changes in large-scale electrophysiological networks over a 6-week training period during which participants practiced a series of motor sequences during 30 home training sessions. Our findings showed that brain networks become more flexible with learning in all the frequency bands from theta to gamma ranges. We found consistent increase of flexibility in the prefrontal and limbic areas in the theta and alpha band, and over somatomotor and visual areas in the alpha band. Specific to the beta rhythm, we revealed that higher flexibility of prefrontal regions during the early stage of learning strongly correlated with better performance measured during home training sessions. Our findings provide novel evidence that prolonged motor skill practice results in higher, frequency-specific, temporal variability in brain network structure.

Cardiorespiratory fitness modulates prestimulus EEG microstates during a sustained attention task.

Higher cardiorespiratory fitness is associated with an increased ability to perform sustained attention tasks and detect rare and unpredictable signals over prolonged periods. The electrocortical dynamics underlying this relationship were mainly investigated after visual stimulus onset in sustained attention tasks. Prestimulus electrocortical activity supporting differences in sustained attention performance according to the level of cardiorespiratory fitness have yet to be examined. Consequently, this study aimed to investigate EEG microstates 2 seconds before the stimulus onset in 65 healthy individuals aged 18-37, differing in cardiorespiratory fitness, while performing a psychomotor vigilance task. The analyses showed that a lower duration of the microstate A and a higher occurrence of the microstate D correlated with higher cardiorespiratory fitness in the prestimulus periods. In addition, increased global field power and occurrence of microstate A were associated with slower response times in the psychomotor vigilance task, while greater global explained variance, coverage, and occurrence of microstate D were linked to faster response times. Our collective findings showed that individuals with higher cardiorespiratory fitness exhibit typical electrocortical dynamics that allow them to allocate their attentional resources more efficiently when engaged in sustained attention tasks.

Raw eye tracking data of healthy adults reading aloud words, pseudowords and numerals.

This paper describes data from de Chambrier et al. (2023). The dataset [2] contains raw eye tracking data of 36 healthy adults, collected using an EyeLink 1000 (SR Research Ltd., ON, Canada) during an on-screen reading task. Participants read 96 items including words, pseudowords and numerals. Each item was presented at the center of the screen until the participant produced an oral response and pressed the keyboard's space bar. Part of the data were analyzed to extract key metrics such as fixation number, fixation duration, saccade number, and saccade amplitude identified by the EyeLink 1000 [1]. Reuse potential includes (but is not limited to) pupil diameter data analysis, identification of fixations and saccades using custom algorithms, and secondary analyses using participant demographics (age, gender) as independent variables.

Reading numbers is harder than reading words: An eye-tracking study.

We recorded the eye movements of adults reading aloud short (four digit) and long (eight to 11 digit) Arabic numerals compared to matched-in-length words and pseudowords. We presented each item in isolation, at the center of the screen. Participants read each item aloud at their pace, and then pressed the spacebar to display the next item. Reading accuracy was 99 %. Results showed that adults make 2.5 times more fixations when reading short numerals compared to short words, and up to 7 times more fixations when reading long numerals with respect to long words. Similarly, adults make 3 times more saccades when reading short numerals compared to short words, and up to 9 times more saccades when reading long numerals with respect to long words. Fixation duration and saccade amplitude stay almost the same when reading short numerals with respect to short words. However, fixation duration increases by ∼50 ms when reading long numerals (∼300 ms) with respect to long words (∼250 ms), and saccade amplitude decreases up to 0.83 characters when reading long numerals with respect to long words. The pattern of findings for long numerals-more and shorter saccades as well as more and longer fixations-shows the extent to which reading long Arabic numerals is a cognitively costly task. Within the phonographic writing system, this pattern of eye movements stands for the use of the sublexical print-to-sound correspondence rules. The data highlight that reading large numerals is an unautomatized activity and that Arabic numerals must be converted into their oral form by a step-by-step process even by expert readers.

Lung and diaphragm ultrasound in noninvasive respiratory support: A real tool or fashion?

Introduction: Over the past few years, there has been an increase in lung and diaphragm ultrasound applications as a tool to evaluate the outcomes and settings of noninvasive respiratory supports. However, actual clinical practices in this field are yet to be known. The aim of this study was to investigate the current clinical utilization of ultrasound for noninvasive respiratory supports on an international level. Materials and Methods: The study employed an online survey consisting of 32 items, which was sent via email to intensivists, pulmonologists, emergency medicine physicians, and other specialists with expertise in using ultrasound and/or noninvasive respiratory supports. Result: We collected 52 questionnaires. The ultrasound study of diaphragm dysfunction was well-known by the majority of respondents (57.7%). Diaphragm performance was used as a weaning failure predictor (48.5%), as a predictor of noninvasive ventilation failure (38.5%) and as a tool for the ventilator settings adjustment (30.8%). In patients with acute respiratory failure, 48.1% used ultrasound to assess the damaged lung area to set up ventilatory parameters, 34.6% to monitor it after noninvasive ventilation application, and 32.7% to match it with the ventilatory settings for adjustment purposes. When administering high flow nasal cannula - oxygen therapy, 42.3% of participants used ultrasound to evaluate lung involvement and assess flow parameters. Conclusions: Lung and diaphragm ultrasound is an established clinical practice to evaluate noninvasive respiratory supports outcomes and settings. Further studies are needed to evaluate the educational aspects to increase confidence and indications for its use.

The field of expertise modulates the time course of neural processes associated with inhibitory control in a sport decision-making task.

Inhibitory control (IC), the ability to suppress inappropriate actions, can be improved by regularly facing complex and dynamic situations requiring flexible behaviors, such as in the context of intensive sport practice. However, researchers have not clearly determined whether and how this improvement in IC transfers to ecological and nonecological computer-based tasks. We explored the spatiotemporal dynamics of changes in the brain activity of three groups of athletes performing sport-nonspecific and sport-specific Go/NoGo tasks with video footages of table tennis situations to address this question. We compared table tennis players (n = 20), basketball players (n = 20) and endurance athletes (n = 17) to identify how years of practicing a sport in an unpredictable versus predictable environment shape the IC brain networks and increase the transfer effects to untrained tasks. Overall, the table tennis group responded faster than the two other groups in both Go/NoGo tasks. The electrical neuroimaging analyses performed in the sport-specific Go/NoGo task revealed that this faster response time was supported by an early engagement of brain structures related to decision-making processes in a time window where inhibition processes typically occur. Our collective findings have relevant applied perspectives, as they highlight the importance of designing more ecological domain-related tasks to effectively capture the complex decision-making processes acquired in real-life situations. Finally, the limited effects from sport practice to laboratory-based tasks found in this study question the utility of cognitive training intervention, whose effects would remain specific to the practice environment.

Electrocortical correlates of the association between cardiorespiratory fitness and sustained attention in young adults.

Cardiorespiratory fitness is thought to be positively related to sustained attention. However, the underlying mechanisms of this relationship have yet to be fully elucidated. The objective of this study was to i) explore the relationship between cardiorespiratory fitness and sustained attention in 72 young adults (18-37 years old) and ii) provide insight on the electrocortical dynamics supporting sustained attention performance in individuals differing in cardiorespiratory fitness by means of EEG topographic analyses and source localization. Behaviorally, cardiorespiratory fitness was related to faster response times and higher accuracy in the psychomotor vigilance task even when adjusting the model with confounding variables such as age, body mass index and chronic physical activity. However, there was no relationship between cardiorespiratory fitness and the classic vigilance decrement observed in the sustained attention task. At the electrocortical level, higher cardiorespiratory fitness was related to increased global field power (310-333 ms poststimulus) localized in the posterior cingulate cortex (BA 30) followed by changes in scalp topographies around the P3b ERP component (413-501 ms poststimulus), which corresponded to earlier activation of the supplementary motor areas (BA 6). This is the first study using high-density EEG, which harnesses the whole spatiotemporal dynamics of the relationship between cardiorespiratory fitness and sustained attention in young adults.

Comments on "Post severe COVID-19 infection lung damages study. The experience of early three months multidisciplinary follow-up" by De Michele et al.

Dear Editor, we read the original study by De Michele et al. titled "Post severe COVID-19 infection lung damages study. The experience of early three months multidisciplinary follow-up" with great interest...

Age-Related Differences in Resting-State EEG and Allocentric Spatial Working Memory Performance.

During normal aging resting-state brain activity changes and working memory performance declines as compared to young adulthood. Interestingly, previous studies reported that different electroencephalographic (EEG) measures of resting-state brain activity may correlate with working memory performance at different ages. Here, we recorded resting-state EEG activity and tested allocentric spatial working memory in healthy young (20-30 years) and older (65-75 years) adults. We adapted standard EEG methods to record brain activity in mobile participants in a non-shielded environment, in both eyes closed and eyes open conditions. Our study revealed some age-group differences in resting-state brain activity that were consistent with previous results obtained in different recording conditions. We confirmed that age-group differences in resting-state EEG activity depend on the recording conditions and the specific parameters considered. Nevertheless, lower theta-band and alpha-band frequencies and absolute powers, and higher beta-band and gamma-band relative powers were overall observed in healthy older adults, as compared to healthy young adults. In addition, using principal component and regression analyses, we found that the first extracted EEG component, which represented mainly theta, alpha and beta powers, correlated with spatial working memory performance in older adults, but not in young adults. These findings are consistent with the theory that the neurobiological bases of working memory performance may differ between young and older adults. However, individual measures of resting-state EEG activity could not be used as reliable biomarkers to predict individual allocentric spatial working memory performance in young or older adults.

[Risk of diabetes mellitus during regular long-term inhaled glucocorticoid treatment in COPD patients: narrative review of the literature.] / Rischio di diabete mellito durante il trattamento regolare a lungo termine con glucocorticoidi per via inalatoria nei pazienti con BPCO: revisione narrativa della letteratura.

Glucocorticoids are anti-inflammatory drugs used in combination with inhaled bronchodilators, such as ß2-agonists and antimuscarinics, for the treatment of stable chronic obstructive pulmonary disease (COPD), to improve respiratory symptoms, such as exertional dyspnoea, and to decrease the risk of future COPD exacerbations. However, it remains controversial whether their regular long-term use increases the risk of developing diabetes mellitus. The objective of this narrative review is therefore to analyse all the randomized controlled trials performed in patients with stable COPD to identify the risk of new onset diabetes mellitus during a long-term (at least 52 weeks) regular treatment with inhaled glucocorticoids alone compared to placebo. From a literature search on PubMed, 19 studies fulfilling these criteria have been identified. The inhaled glucocorticoids administered were: fluticasone propionate (7 studies), budesonide (6 studies), mometasone furoate (3 studies), beclomethasone dipropionate (1 study), triamcinolone acetonide (1 study), and fluticasone furoate (1 study) respectively. Only 3 out of the 19 trials identified in our narrative review reported data on diabetes mellitus, and in these the incidence of diabetes mellitus was not significantly different in both treatment arms (inhaled glucocorticoids and placebo), regardless of the type of glucocorticoid used.

Resting-State EEG Microstates Parallel Age-Related Differences in Allocentric Spatial Working Memory Performance.

Alterations of resting-state EEG microstates have been associated with various neurological disorders and behavioral states. Interestingly, age-related differences in EEG microstate organization have also been reported, and it has been suggested that resting-state EEG activity may predict cognitive capacities in healthy individuals across the lifespan. In this exploratory study, we performed a microstate analysis of resting-state brain activity and tested allocentric spatial working memory performance in healthy adult individuals: twenty 25-30-year-olds and twenty-five 64-75-year-olds. We found a lower spatial working memory performance in older adults, as well as age-related differences in the five EEG microstate maps A, B, C, C' and D, but especially in microstate maps C and C'. These two maps have been linked to neuronal activity in the frontal and parietal brain regions which are associated with working memory and attention, cognitive functions that have been shown to be sensitive to aging. Older adults exhibited lower global explained variance and occurrence of maps C and C'. Moreover, although there was a higher probability to transition from any map towards maps C, C' and D in young and older adults, this probability was lower in older adults. Finally, although age-related differences in resting-state EEG microstates paralleled differences in allocentric spatial working memory performance, we found no evidence that any individual or combination of resting-state EEG microstate parameter(s) could reliably predict individual spatial working memory performance. Whether the temporal dynamics of EEG microstates may be used to assess healthy cognitive aging from resting-state brain activity requires further investigation.

The role of non-invasive ventilation in weaning and decannulating critically ill patients with tracheostomy: A narrative review of the literature.

INTRODUCTION: Invasive mechanical ventilation (IMV) is associated with several complications. Placement of a long-term airway (tracheostomy) is also associated with short and long-term risks for patients. Nevertheless, tracheostomies are placed to help reduce the duration of IMV, facilitate weaning and eventually undergo successful decannulation. METHODS: We performed a narrative review by searching PubMed, Embase and Medline databases to identify relevant citations using the search terms (with synonyms and closely related words) "non-invasive ventilation", "tracheostomy" and "weaning". We identified 13 publications comprising retrospective or prospective studies in which non-invasive ventilation (NIV) was one of the strategies used during weaning from IMV and/or tracheostomy decannulation. RESULTS: In some studies, patients with tracheostomies represented a subgroup of patients on IMV. Most of the studies involved patients with underlying cardiopulmonary comorbidities and conditions, and primarily involved specialized weaning centres. Not all studies provided data on decannulation, although those which did, report high success rates for weaning and decannulation when using NIV as an adjunct to weaning patient off ventilatory support. However, a significant percentage of patients still needed home NIV after discharge. CONCLUSIONS: The review supports a potential role for NIV in weaning patients with a tracheostomy either off the ventilator and/or with its decannulation. Additional research is needed to develop weaning protocols and better characterize the role of NIV during weaning.

Which are the factors influencing NIV adaptation and tolerance in ALS patients?

Amyotrophic lateral sclerosis (ALS) is a multisystemic disease compromising both the neuromuscular system and the cognitive status. Non-invasive ventilation (NIV) has been shown to improve survival and quality of life in ALS patients with respiratory failure, but scanty literature investigated which are the predictors of NIV tolerance. The aim of this study was to evaluate the impact of functional, cognitive, neurobehavioral, and respiratory status on NIV compliance and tolerance in patients with ALS. We retrospectively evaluated clinical data of ALS patients who consecutively underwent a NIV trial during hospitalization. Cognitive and neurobehavioral assessments have been performed using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), the Hospital Anxiety and Depression Scale (HADS), the Frontal Assessment Battery (FAB), the Raven's 47 Colored Progressive Matrices (PM47), and the Neurobehavioral Rating Scale Revised (NRSR). Seventy-two patients (mean age ± SD; 63.9 ± 10.6 years) were included. Patients adapted were 63/72 (87.5%). The average time of adaptation was 7.82 ± 5.27 days. The time required to reach a satisfying NIV adaptation was significantly related to the presence of sialorrhea (p = 0.02), respiratory status (Borg Dyspnoea Scale, p = 0.006, and ALS-FRS-R respiratory subscore, p = 0.03) and behavioral and cognitive impairment (NRSR-F1, p = 0.04, NRSR- F5, p = 0.04). Presence of sialorrhea and neurobehavioral impairment, and absence of respiratory symptoms are negative predictors of NIV adaptation. This study highlights the need of a multidisciplinary patient-tailored approach including cognitive-behavioral assessment and a psychological support program to optimize patient's training and compliance to NIV.

Role of Atypical Chemokines and Chemokine Receptors Pathways in the Pathogenesis of COPD.

Chronic obstructive pulmonary disease (COPD) represents a heightened inflammatory response in the lung generally resulting from tobacco smoking-induced recruitment and activation of inflammatory cells and/or activation of lower airway structural cells. Several mediators can modulate activation and recruitment of these cells, particularly those belonging to the chemokines (conventional and atypical) family. There is emerging evidence for complex roles of atypical chemokines and their receptors (such as high mobility group box 1 (HMGB1), antimicrobial peptides, receptor for advanced glycosylation end products (RAGE) or toll-like receptors (TLRs)) in the pathogenesis of COPD, both in the stable disease and during exacerbations. Modulators of these pathways represent potential novel therapies for COPD and many are now in preclinical development. Inhibition of only a single atypical chemokine or receptor may not block inflammatory processes because there is redundancy in this network. However, there are many animal studies that encourage studies for modulating the atypical chemokine network in COPD. Thus, few pharmaceutical companies maintain a significant interest in developing agents that target these molecules as potential antiinflammatory drugs. Antibody-based (biological) and small molecule drug (SMD)-based therapies targeting atypical chemokines and/or their receptors are mostly at the preclinical stage and their progression to clinical trials is eagerly awaited. These agents will most likely enhance our knowledge about the role of atypical chemokines in COPD pathophysiology and thereby improve COPD management.