Background: In Transcranial Direct Current Stimulation (tDCS) the injected current gets distributed across the brain areas. The motive is to stimulate the target region-of-interest (ROI), while minimizing the current in non-target ROIs. For this purpose, determining the appropriate current-dose for an individual is difficult. Aim: To introduce Dose-Target-Determination-Index (DTDI) to quantify the focality of tDCS and examine the dose-focality relationship in three different populations. Method: Here, we extended our previous toolbox i-SATA to the MNI reference space. After a tDCS montage is simulated for a current-dose, the i-SATA(MNI) computes the average (over voxels) current density for every region in the brain. DTDI is the ratio of average current density at target ROI to the ROI with maximum value (peak region). Ideally target ROI should be the peak region, so DTDI shall range from 0 to 1. Higher the value, the better the dose. We estimated the variation of DTDI within and across individuals using T1-weighted brain images of 45 males and females distributed equally across three age groups- (a) Young adults (20 ≥ x ˂ 40 years), (b) Mid adults (40 ≥ x ˂ 60 years), and (c) Older adults (60 ≥ x ˂ 80 years). DTDI’s were evaluated for the frontal montage with electrodes at F3 and right supra-orbital for three current doses 1mA, 2mA, and 3mA with the target ROI at left middle frontal gyrus. Result: As the dose is incremented, DTDI may show (a) increase, (b) decrease, and (c) no change across the individuals. The focality decreases with age and the decline is stronger in males. Higher current dose at older age can enhance the focality of stimulation. Conclusion: DTDI provides information on which tDCS current dose will optimize the focality of stimulation. DTDI recommended dose should be prioritised based on the age (> 40 years) and sex (especially males) of an individual. The toolbox i-SATA(MNI) is freely available.

Abstract Introduction: In the last thirty years, brain neuromodulation techniques have been used as an alternative to pharmacological treatment of neurological disorders. Parkinson's disease (PD) is a neurodegenerative disorder leading to bradykinesia, rest tremor, postural changes, and non-motor symptoms such as depression, anxiety, sleep disorders, pain, and cognitive decline that compromises executive functions (EFs), responsible for the orderly execution of behaviors and tasks of daily life and intentional and directed actions. To this date, a few studies with transcranial direct current stimulation (tDCS) have shown beneficial effects in PD patients concerning specific motor and non-motor symptoms, targeting the motor cortex and/or prefrontal regions. Objective: The main objective of this study was to evaluate the effects of left prefrontal tDCS across a broad spectrum of motor and non-motor symptoms of PD using established validated scales. Method: Single-blind randomized clinical trial with 18 volunteers with PD, aged between 45 and 80 years (66.1 ± 9.65), who met inclusion and exclusion criteria. Participants were submitted to assessments of motor and non-motor functions employing psychometric scales and tests to evaluate EFs and were randomly divided into two groups: control (sham stimulation) and experimental (active stimulation). All participants were involved in three separate tDCS sessions. The anode was positioned over the left dorsolateral prefrontal cortex and the cathode over the right supraorbital region, with a direct current intensity of 2mA, lasting 20 minutes. At the end of the three sessions, all participants were reassessed. Results: Significant effects of tDCS on non-motor functions were observed for cognition (verbal fluency of actions, clock copy test, appointment by visual confrontation, and verbal memory with immediate free recall) and subjective assessment of sleep quality (overall restlessness and discomfort in the arms and legs at night, leg and arm cramps at night and distressing dreams). There was also an improvement in the rate of errors and successes for congruent and incongruent stimuli of the Stroop Test. The beneficial effects on motor function were decreased rigidity, improved gait, and greater agility in the finger-tapping test. Conclusion: Three tDCS sessions showed positive results for participants with PD, producing significant improvements in various motor and non-motor functions, including sleep quality, cognition, and EFs. Additionally, the present results indicate that tDCS neuromodulation of the left dorsolateral prefrontal cortex region is feasible, safe, and provides significant objective benefits for PD patients.

ADHD, a neurodevelopmental condition, is distinguished by a triad of symptoms including inattention, hyperactivity, and impulsivity. It is frequently accompanied by comorbidities such as anxiety, depression, and learning disabilities. As a result, clinicians often face challenges in accurately diagnosing ADHD and differentiating it from other conditions. As a prospective remedy for ADHD, scientists have investigated Transcranial Direct Current Stimulation (tDCS), a non-invasive technique of stimulating the brain. It involves applying low-intensity electrical currents to specific regions of the brain to modulate neural activity. This review paper aims to provide an overview of the comorbidities associated with ADHD and the differential diagnosis of the condition. It also explores the potential of tDCS as a treatment option for ADHD, including its mechanisms of action and efficacy in improving ADHD symptoms. The comorbidities discussed in this review include anxiety disorders, mood disorders, and substance use disorders. These comorbidities are frequently seen in individuals with ADHD and can complicate the diagnosis and treatment of the condition. The paper also highlights the importance of considering comorbidities when assessing ADHD, as well as the potential impact of these conditions on treatment outcomes. The differential diagnosis section of the paper explores conditions that can present with symptoms similar to ADHD, such as anxiety disorders, mood disorders, and learning disabilities. It emphasizes the need for a thorough assessment and differential diagnosis to identify ADHD and differentiate it from other conditions accurately. The final section of the paper discusses the potential of tDCS as a treatment option for ADHD. It examines the mechanisms of action of tDCS and its efficacy in improving ADHD symptoms, including attention, hyperactivity, and impulsivity. It also explores the potential for tDCS to improve comorbid conditions associated with ADHD. Overall, this review provides a comprehensive overview of comorbidities and differential diagnoses in ADHD and the potential of tDCS as a treatment option. The paper highlights the importance of a thorough assessment and personalized treatment plan for individuals with ADHD, particularly those with comorbidities.

Background: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low levels of a constant current via scalp electrodes to specifically targeted areas of the brain. The effects of tDCS on whole-body exercise performance has been of interest in recent literature. The purpose of the current investigation was to investigate if tDCS, administered via Halo Sport, influences time trial performance in trained cyclists, and if changes in exercise performance are associated with prefrontal cortex (PFC) activation and/or muscle oxygenation (SmO2). Methods: Twelve recreationally trained cyclists volunteered to participate in two 10-kilometer time trials following 20 minutes of tDCS or a sham condition. Results: T-tests showed there was no significant difference in performance (time to completion) or physiological measures (BLa-, HR, SmO2, PFC oxygenation) between the Halo and sham conditions. Conclusions: These results indicate that the application of tDCS via Halo Sport does not induce changes in exercise performance or related physiological parameters during a 10-kilometer cycling time trial.

Transcranial direct current stimulation (tDCS) is acknowledged for its non-invasive modulation of neuronal activity in psychiatric disorders. However, its application in insomnia research yields varied outcomes depending on different tDCS types and patient conditions. Our primary objective is to elucidate its efficiency and uncover the underlying mechanisms in insomnia treatment. We hypothesized that anodal prefrontal cortex stimulation activates glutaminergic projections from the infralimbic cortex (IL) to ventrolateral preoptic area (VLPO) to promote sleep. After administering 0.06 mA of electrical currents for 8 minutes, our results indicate significant non-rapid eye movement (NREM) enhancement in naïve mice within the initial 3 hours post-stimulation, persisting up to 16-24 hours. In the insomnia group, tDCS enhanced NREM sleep bout numbers during acute stress response and improved NREM and REM sleep duration in subsequent acute insomnia. Sleep quality, assessed through NREM delta powers, remains unaffected. Interference of the IL-VLPO pathway, utilizing designer receptors exclusively activated by designer drugs (DREADDs) with the cre-DIO system, partially blocked tDCS's sleep improvement in stress-induced insomnia. This study elucidated that the activation of the IL-VLPO pathway mediates tDCS's effect on stress-induced insomnia. These findings support the understanding of tDCS effects on sleep disturbances, providing valuable insights for future research and clinical applications in sleep therapy.

Objective: Cerebrovascular accidents are the second leading cause of death and the third leading cause of disability worldwide. We hypothesized that cerebellar transcranial direct current stimulation (ctDCS) of the dentate nuclei and the lower-limb representations in the cerebellum can improve standing balance functional reach in chronic (> 6 months’ post-stroke) stroke survivors. Materials and Methods: Magnetic resonance imaging(MRI) based subject-specific electric field was computed across 10 stroke survivors and one healthy MRI template to find an optimal bipolar bilateral ctDCS montage to target dentate nuclei and lower-limb representations (lobules VII-IX). Then, in a repeated-measure crossover study on 5 stroke survivors, we compared 15minutes of 2mA ctDCS based on the effects on successful functional reach(%) during standing balance task. Three-way ANOVA investigated the factors of interest– brain regions, montages, stroke participants, and their interactions.Results: “One-size-fits-all” ctDCS montage for the clinical study was found to be bipolar PO9h – PO10h for dentate nuclei and bipolar Exx7–Exx8 for lobules VII-IX with contalesional anode. Bipolar PO9h–PO10h ctDCS performed significantly (alpha=0.05) better in facilitating successful functional reach (%) when compared to bipolar Exx7–Exx8 ctDCS. Furthermore, a linear relationship between successful functional reach (%) and electric field strength was found where bipolar PO9h–PO10h montage resulted in a significantly (alpha=0.05) higher electric field strength when compared to bipolar Exx7–Exx8 montage for the same 2mA current. Conclusion: We presented a rational neuroimaging based approach to optimize deep ctDCS of the dentate nuclei and lower limb representations in the cerebellum for post-stroke balance rehabilitation.

Apraxia of speech is a persistent speech motor disorder that affects speech intelligibility. Studies on speech motor disorders with transcranial Direct Current Stimulation (tDCS) have been mostly directed to post-stroke aphasia. Only a few tDCS studies have focused on apraxia of speech or childhood apraxia of speech (CAS), and no study has investigated individuals with CAS and people with trisomy 21 (T21, Down Syndrome). This study examined the effects of tDCS combined with a motor learning task in developmental apraxia of speech co-existing with T21 (ReBEC RBR-5435x9). The accuracy of speech sound production of nonsense words (NSWs) during Rapid Syllable Transition Training (ReST) under 10 sessions of anodal tDCS (1.5 mA, 25 cm) over the Broca’s area with cathode over the contralateral region was compared to 10 sessions of sham-tDCS and 4 control sessions in a 20-year-old male individual with T21 presenting moderate-severe childhood apraxia of speech (CAS). The accuracy for NSWs production progressively improved (gain 40%) under tDCS only (sham-tDCS and control sessions showed <20% gain). A decrease in speech severity from moderate-severe to mild-moderate indicated transfer effects in speech production. The speech accuracy under tDCS was correlated with Wernicke’s area activation (P3 current source density), which in turn, was correlated with the activation of the left supramarginal gyrus and the Sylvian Parietal Temporal Junction. Repetitive bihemispheric tDCS paired with ReST may have facilitated the speech sound acquisition in a young adult with T21 and CAS, possibly by recruiting brain regions required for the phonological working memory.

Introduction: The transcranial direct current stimulation (tDCS) is a promising technique for brain modulation after cerebrovascular accident (CVA). This treatment modality has been previously studied in the recovery of patients. The aim of this review is to analyze the evidence in the ap-plication of tDCS in the recovery of gait disturbance in stroke patients. Methods: This review was conducted according to the recommendations of the PRISMA statement. Three different elec-tronic databases were searched for relevant results: PubMed, Scopus, and Cochrane. We included reviews and meta-analyses that only considered randomized controlled trials (RCTs) that inves-tigated the effects of transcranial direct electrical stimulation, in combination or not with other physiotherapy treatment, on gait recovery. Results: Thirteen studies with a total of 195 RCTs were included. Data on population, outcome measures, protocols and outcomes were extracted. The Amstar-2 scale and the GRADE system of certainty of evidence were used. Only one study re-ceived high certainty of evidence, 5 received low certainty of evidence and 7 received critically low certainty of evidence. Conclusions: Although the tDCS produces positive changes in gait recovery in spatio-temporal parameters, mobility, endurance, strength and motor function, there is insuf-ficient evidence to recommend this treatment.

Stroke often results in impaired gait, which can limit community ambulation and the quality of life. Recent works have shown the feasibility of transcranial Direct Current Stimulation (tDCS) as an adjuvant treatment to facilitate gait rehabilitation. Since the cerebellum plays an essential role in balance and movement coordination, which is crucial for independent overground ambulation, so, we investigated the effects of cerebellar tDCS (ctDCS) on the post-stroke overground gait performance in chronic stroke survivors. Fourteen chronic post-stroke male subjects were recruited based on convenience sampling at the collaborating hospitals where ten subjects finally participated in the ctDCS study. We evaluated the effects of two ctDCS montages with 2mA direct current, a) optimized configuration for dentate stimulation with 3.14cm² disc anode at PO10h (10/5 EEG system) and 3.14cm² disc cathode at PO9h (10/5 EEG system), and b) optimized configuration for leg lobules VII-IX stimulation with 3.14cm² disc anode at Exx8 (electrodes defined by ROAST) and 3.14cm² disc cathode at Exx7. We found ctDCS to be acceptable by all the exposed subjects. The ctDCS intervention had an effect on the 'Normalised Step length Affected side' (p=0.1) and 'Gait Stability Ratio' (p=0.0569), which was found using Wilcoxon signed-rank test at 10% significance level. Also, ctDCS montage specific effect was found using a two-sided Wilcoxon rank-sum test at a 5% significance level for 'Step Time Affected Leg' (p=0.0257) and '%Stance Time Unaffected Leg' (p=0.0376). Moreover, the changes in the quantitative gait parameters across both the montages were found to be correlated to the mean electric field strength in the lobules based on partial least squares regression analysis (R² statistic = 0.6574) where the mean electric field strength at the cerebellar lobules, Vermis VIIIb, Ipsilesional IX, Vermis IX, Ipsilesional X, had the most loading. In conclusion, our feasibility study indicated the potential of a single session of ctDCS to contribute to the immediate improvement in the balance and gait performance in terms of gait-related indices and clinical gait measures.

Purpose: Dysarthria, a neurological injury of the motor component of the speech circuitry, is of common consequences of traumatic brain injury (TBI). Palilalia is a speech disorder characterized by involuntary repetition of words, phrases, or sentences. Based on the evidence supporting the effectiveness of transcranial direct current stimulation (tDCS) in some speech and language disorders, we hypothesized that using tDCS would enhances the effectiveness of speech therapy in a client with chronic dysarthria following TBI. Method: We applied the constructs of the “Be Clear” protocol, a relatively new approach in speech therapy in dysarthria, together with tDCS on a chronic subject who affected by dysarthria and palilalia after TBI. Since there was no research on the use of tDCS in such cases, regions of interest (ROIs) were identified based on deviant brain electrophysiological patterns in speech tasks and resting state compared with normal expected patterns using the Quantitative Electroencephalography (QEEG) analysis. Results: Measures of perceptual assessments of intelligibility, an important index in the assessment of dysarthria, ​​were superior to the primary protocol results immediately and 4 months after intervention. We did not find any factor other than the use of tDCS to justify this superiority. The percentage of repeated words, an index in palilalia assessment, had a remarkable improvement immediately after intervention but fell somewhat after 4 months. We justified this case with subcortical origins of palilalia. Conclusion: Our present case-based findings suggested that applying tDCS together with speech therapy may improve intelligibility in similar case profiles as compared to traditional speech therapy. To reconfirm the effectiveness of the above approach in cases with dysarthria following TBI, more investigation need to be pursued.

Transcranial magnetic stimulation, TMS, has been an innovative method of demure neuromodulation. This paper aims to delve into the different forms of its existence and to evaluate the use of TMS in five psychiatric disorders; Parkinson’s disease, schizophrenia, obsessive-compulsive disorder, major depressive disorder, and major anxiety disorder. Literature pertaining to the use of TMS in treating these specific diseases will be analyzed, and its efficacy and mechanisms will be explored. The literature will be evaluated through sources with established facts and research studies demonstrating function, potency, or inefficacy. TMS poses a method to have a more explicit effect on the regions of the brain, and the exploration of its use in the treatment of psychiatric diseases poses new possibilities in the treatment of psychiatric disorders. Venturing into the options it could have in a sole or combinatorial setting could provide penetrating insight into innovative forms of treatment and research.

Neuropathic pain is caused by a lesion or disease of the somatosensory system and is one of the most incapacitating pain types, representing a significant non met medical need. Due to the increase in research in the field and since innovative therapeutic strategies are required, namely in intractable neuropathic pain, neurostimulation has been used. Within this approaches, transcranial magnetic stimulation (TMS) that uses a transient magnetic field to produce electrical currents over the cortex emerges in the literature. Since this is an area in expansion and due to the putative role of TMS, we performed a bibliometric analysis in Scopus with the primary objective of identify the scientific production related to the use of TMS to manage neuropathic pain. The research had no restrictions and the analysis focused on the characteristics of the literature retrieved, scientific collaboration and main research topics from inception to July 6, 2023. A total of 474 articles were collected. A biggest co-occurrence between the terms “neuropathic pain” and “transcranial magnetic stimulation” was obtained. The journal “Clinical Neurophysiology” leads the Top 5 most productive sources. The United States is the most productive country with 50% of the documents being “review articles” followed by France with 56% of the documents being “original articles”. Lefaucheur, JP and Saitoh, Y are the two most influents authors. The most frequent type of documents was “original article”. This study allows to perform a general overview in the field of TMS application for neuropathic pain and is useful to establish future directions of research in this field.

Cannabis is the most widely cultivated, trafficked and abused illicit drug (“WHO | Cannabis,” n.d.; “World Drug Report 2020,” n.d.). In 2018, an estimated 192 million people aged 15-64 years used cannabis for nonmedical purposes globally (Degenhardt et al., 2013). The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated that, across the globe, there were more than 22·1 million people with cannabis dependence (Degenhardt et al., 2018). Moreover, the same study calculated that cannabis dependence could be accounted for 646 thousand Disability Adjusted Life Years, globally. Importantly, cannabis dependence mostly affects young adults (20-24 years), and thus has significant negative impact on the growth and productivity of not only these individuals but also to the societies and nations (Degenhardt et al., 2013). In addition to the dependence syndrome, cannabis use is associated with increased risk of psychosis, cognitive dysfunction, academic problems, and road side accidents (Volkow et al., 2014). A review showed a fairly consistent associations between cannabis use and both lower educational attainment and increased reported use of other illicit drugs (Macleod et al., 2004). In the United States, Cannabis Use Disorder (CUD) is an escalating problem in young adults by legalization (Cerdá et al., 2020) where National Survey on Drug Use and Health reported increased prevalence from 5.1% in 2015 to 5.9% in 2018 in 18-25 year olds (“2019 NSDUH Detailed Tables | CBHSQ Data,” n.d.). The psychoactive effects are due to type 1 cannabinoid receptor (CB1), the cannabinoid binding protein, that are highly expressed in the cerebellar cortex (Marcaggi, 2015). CB1 is primarily found in the molecular layer at the most abundant synapse type in the cerebellum (Marcaggi, 2015) that can shape the spike activity of cerebellar Purkinje cell (Brown et al., 2019). Moreover, granule cell to Purkinje cell synaptic transmission can trigger endocannabinoid release (Alger and Kim, 2011), which may be important for information processing by cerebellar molecular layer interneurons (Dorgans et al., 2019). This suggests that endocannabinoids could be essential to neurocognitive aspects of cerebellar function (Di Marzo et al., 2015)^,(Marcaggi, 2015)^,(Alger and Kim, 2011). Accumulating evidence also suggests cerebellar modulation of the reward circuitry and social behaviour, via direct cerebellar innervation of the ventral tegmental area (VTA) including dopamine cell bodies (A1) in the VTA (Carta et al., 2019). The VTA-dopamine (DA) signalling in the nucleus accumbens (NAc) and the medial prefrontal cortex (mPFC) (Lohani et al., 2019) play a key role in motivatedbehaviours and cognition. Cerebellar neuropathological changes can result in aberrant dopaminergic activity in the NAc and mPFC (ROGERS et al., 2011)^,(Lohani et al., 2019). Therefore, there is a critical need to determine how cerebellum modulate limbic VTA-DA signalling. Cerebellar Non-Invasive Brain Stimulation (NIBS) is postulated to be most relevant in CUD since endocannabinoids are essential to cerebellar function that includes reward-related behaviours, information processing, and cognitive control. (Di Marzo et al., 2015)^,(Marcaggi, 2015)^,(Alger and Kim, 2011). Furthermore, cerebellar NIBS can facilitate training of cognitive control in CUD during a during visual cue reactivity paradigm using a mobile virtual reality (VR) interface that can also allow remote delivery of cerebellar NIBS in conjunction with VR-based cognitive training for home-based intervention. Specifically, transcranial electrical stimulation (tES) can be translatable to low-cost (<$150) mobile devices that can be used in a low resource home-based setting (Carvalho et al., 2018).

Background: Cervical myelopathy (CM) is a common cause of morbidity and disability in patients with mucopolysaccharidosis (MPS) and, therefore, early detection is crucial for best surgical intervention and follow-up. Transcranial Magnetic Stimulation (TMS) non-invasively evaluates the conductivity along the cortico-spinal tract, also allowing preclinical diagnosis and monitoring. Methods: motor evoked potentials (MEPs) to TMS were recorded in a group of 8 patients with MPS-related CM. Responses were obtained during mild tonic contraction through a circular coil applied over the “hot spot” of the first dorsal interosseous and tibialis anterior muscles, bilaterally. Central motor conduction time was estimated as the difference between MEP cortical latency and the peripheral motor conduction time by cervical or lumbar magnetic stimulation. Peak-to-peak MEP amplitude to cortical stimulation and right-to-left difference of each parameter were also measured. Results: TMS revealed abnormal findings from both upper and lower limbs compatible with axonal damage and demyelination in 6 of them. Notably, a subclinical cervical spinal disease was detected before the occurrence of an overt CM in two patients, whereas TMS signs compatible with a CM of variable degree persisted despite surgery in all treated subjects. Conclusions: TMS screening should be performed in MPS patients, before and after surgery.

The capacity to externally control transcranial magnetic stimulation (TMS) devices is becoming increasingly important in brain stimulation research. Here we introduce MAGIC (MAGnetic stimulator Interface Controller), an open-source MATLAB toolbox for controlling Magstim and MagVenture stimulators. MAGIC includes a series of MATLAB functions which allow the user to arm/disarm the stimulator, send triggers, change stimulator settings such as amplitude, interpulse intervals, and frequency, and receive stimulator setting information via a serial port connection between a computer and the stimulator. By providing external control capability, MAGIC enables greater flexibility in designing research protocols which require trial-by-trial changes of device settings to realize a priori trial randomization or interactive ad hoc adjustment of parameters during an ongoing experiment. MAGIC thus helps to prevent experimental confounds related to the block-wise variation of parameters and facilitates the integration of TMS with cognitive/sensory tasks, and the development of more adaptive brain state-dependent brain stimulation protocols.

Background: Objectives. The objective of this study was to compare the efficacy of direct current stimulation (DCS) applied at the transcranial, suboccipital and spinal level on experimental sensory modalities and pain outcome measures in healthy subjects. The hypothesis of this study was that systematic analysis of the efficacy of DCS on modulating evoked thermal and mechanical pain modalities and mechanisms such as endogenous pain modulation in healthy individuals would reveal sensitive outcome measures help develop this technique for the control of chronic pain. Materials and Methods. Database searches were conducted up to December 2019 for randomized controlled trials that performed sham-controlled DCS of experimental sensory modalities and pain outcomes following transcranial, suboccipital and spinal locations in healthy participants. Standardized mean differences with 95% confidence intervals were calculated for sensory modalities, including random-effect metanalysis. Results: Thirty-one studies were included for analysis (647 participants). A significant decrease in pain intensity for active vs sham transcranial stimulation was identified for pain intensity (n=158; SMD=0.79; 95% CI=0.56 to 1.02), a significant increase in heat pain threshold (n=222; SMD=1.16; 95% CI=0.95 to 1.37), and a significant increase in cold pain threshold (n = 155; SMD = 0.77, 95% CI 0.53 to 1.01). No significant modulation of pressure pain threshold was identified with DCS and only a limited number of studies focused on experimental pain modulation following neuromodulation at the suboccipital or spinal level. Conclusions: These results show significant transcranial DCS neuromodulation of pain intensity and on thermal pain modalities. Future studies should focus on endogenous pain and sensory modality modulation with sham-controlled DCS applied at transcranial, suboccipital and spinal locations.

Previous studies on the mechanisms underlying willed actions reported that the premotor cortex may be involved in the construction of motor awareness. However, its exact role is still under investigation. Here we investigated the role of the dorsal premotor cortex (PMd) in motor awareness by modulating its activity applying inhibitory rTMS to PMd, before a specific motor awareness task (under three conditions: without stimulation, after rTMS and after sham stimulation). During the task, subjects had to trace straight lines to a given target, receiving a visual feedback of the line trajectories on a computer screen. Crucially, in most trials the trajectories on the screen were deviated and to produce straight lines, subjects had to correct their movements towards the opposite direction. After each trial, participants were asked to judge whether the line seen on the computer screen corresponded to the line actually drawn. Results show that participants in the no stimulation condition did not recognize the perturbation until 14 degrees of deviation. Importantly, active, but not sham, rTMS significantly modulated motor awareness, decreasing the amplitude of the angle at which participants became aware of the trajectory correction. These results suggest that PMd plays a crucial role in action self- monitoring.

Multiple sclerosis (MS) is an immune-mediated, chronic inflammatory disease of the central nervous system (CNS), characterized by demyelination, axonal degeneration, and cognitive impairment. It also has an important impact on the quality of life of patients and their family members. An estimated 2,500,000 people in the world have multiple sclerosis. Neurophysiological parameters, like sensitivity to demyelination and the strength of excitatory and inhibitory synaptic interactions in the cerebral cortex, can be identified through transcranial magnetic stimulation (TMS) in patients affected by multiple sclerosis (MS). These parameters can be valid and objective parameters that can be correlated with the progression of MS, and can provide reliable indices for the severity of illness and the efficacy of drugs used to treat it. The discovery of specific and detailed neurophysiological parameters as surrogate end points for disease activity could represent an important step in clinical trials. Changes in cortical connectivity have already been demonstrated in MS, but in clinical practice, other measures are usually used to evaluate disease activity. We speculate that TMS may be more effective in identifying disease progression that leads to long-term disability, compared to standard surrogate markers, due to the fact that it represents a direct measure of synaptic transmission(s) in MS.

Transcranial magnetic stimulation (TMS) represents a distinctive technique for non-invasive brain stimulation. Recent advancements in image processing have enabled the enhancement of TMS by integrating magnetic resonance imaging (MRI) modalities with TMS via a neuronavigation system. The aim of this study is to assess the efficacy of navigated TMS for cortical mapping in comparison to surgical mapping using direct electrical stimulation (DES). The study involved 30 neurosurgical procedures for tumors located in or adjacent to the precentral gyrus. The DES points were compared with TMS responses based on the original distances of vectorial modules. There was a notable similarity in the points obtained from the two mapping methods. The distances between the geometric centers of TMS and DCS were 4.85 ± 1.89 mm. A strong correlation was identified between these vectorial points (r = 0.901, p < 0.001). The motor threshold in TMS was highest in the motor cortex adjacent to the tumor compared to the normal cortex (p < 0.001). Patients with deficits exhibited excellent accuracy in both methods. In view of this, TMS demonstrated reliable and precise application in brain mapping, which is a promising method for preoperative functional mapping in motor cortex tumor surgery.

This paper introduces a systematic approach to the design of Direct Current-to-Digital Converter (DCDC) specifically engineered to overcome the limitations of traditional current measurement methodologies in System-on-Chip (SoC) designs. The proposed DCDC addresses critical challenges such as high power consumption, large area requirements, and the need for intermediate analog signals. By incorporating a current mirror in a cascode topology and managing the current across multiple binary-sized branches with the Successive Approximation Register (SAR) logic, the design achieves precise current measurement. A simple comparator, coupled with an isolation circuit, ensures accurate and reliable sensing. Fabricated using the TSMC 180 nm process, the DCDC achieves 8-bit precision without the need for nonlinearity calibration, showcasing remarkable energy efficiency with an energy per conversion of 1.52 pJ, power consumption of 117 µW, and a compact area of 0.016 mm². This innovative approach not only reduces power consumption and area, but also provides a scalable and efficient solution for next-generation semiconductor technologies. The ability to conduct online measurements during both standard operations and in-field conditions significantly enhances the performance and reliability of SoCs, making this DCDC a promising advancement in the field.

Neuromonitoring of the efferent nerve impulses transmission in the spinal cord tracts during surgical scoliosis treatment makes it possible to assess whether the functional status is deteriorating, affecting the procedure's safety. Is there any relationship between pre- and intraoperative motor evoked potentials recordings and does idiopathic scoliosis (IS) surgical correction improve directly the spinal efferent transmission? This study aimed to compare the results of surface recorded electromyography (EMG), electroneurography (ENG, M and F-waves), and especially motor evoked potentials (MEP) from tibialis anterior (TA) muscle bilaterally in 353 girls with the right idiopathic scoliosis (types 1A-4C according to Lenke classification). It has not yet been documented whether the results of MEPs recordings induced by transcranial single magnetic stimulus (TMS, pre – and postoperatively) and trains of electrical stimuli (TES; intraoperatively in T0-before surgery, T1 – after pedicle screws implantation, T2 – after scoliosis curvature distraction and derotation following two rods implantation) can be compared for diagnostic verification of improvement of the spinal neural transmission. The study also attempted to determine whether the constant level of optimal anesthesia during the certain surgical steps of scoliosis treatment affects the parameters of MEPs recorded during neuromonitoring procedures. No neurological deficits have been observed postoperatively. Values of amplitudes but not latencies in MEPs recordings evoked with TMS in IS patients compared before and after surgery indicated a slight improvement in the efferent transmission of neural impulses within the fibers of the spinal tracts postoperatively. Results of all neurophysiological studies in IS patients were significantly asymmetrical and recorded worse on the concave side, suggesting greater neurological motor deficits at p=0.04. This asymmetry had been significantly reduced following IS surgery. The surgeries in IS patients brought significant improvement (p=0.04) in parameters of amplitudes of sEMG recordings, however reflecting still the consequences of the neurogenic injury of TA muscle motor units. ENG studies results indicated the symptoms of the axonal type injury in peroneal motor fibers improved only on the concave side at p=0.04 in parallel with the significant improvement of F-waves parameters, which suggests that surgeries might result in the lumbar ventral roots decompression. There were not detected significant differences in amplitudes or latencies of MEPs induced with TMS or TES comparing the parameters recorded preoperatively (one day before surgery) and intraoperatively in T0. The amplitudes of TES evoked MEPs increased gradually at p=0.04 in the subsequent periods (T1 and T2) of observation. The significant reduction of MEPs latency at p=0.05 was observed only at the end of the IS surgery. Studies on the possible connections between the level of anesthesia fluctuations and the required TMS stimulus strength, as well as the MEPs amplitude changes measured in T0-T2 revealed lack of relationships. It is not likely that they could be the factors influencing the efferent transmission in spinal pathways beside the surgical procedures. Considering that MEPs amplitude parameter reflects the number of axons excited from the motor cortex and transmitting the efferent impulses via spinal descending tracts in the white matter, pre- (TMS evoked) and intraoperative (TES evoked) recordings are reliable for evaluating the patient’s neurological status before and during surgical scoliosis correction procedures. The results of this study indicate an agreement between preoperative and early-intraoperative evaluations with these both diagnostic methods. An increase of MEPs amplitude parameters recorded on both sides after scoliosis surgery proves immediate improvement of the total efferent spinal cord transmission. Considering comparative pre- and postoperative sEMG and ENG recordings it can be concluded that surgeries might directly result in the additional lumbar ventral roots decompression. Our results of the tests on the possible variability of the anesthesia level on the parameters of intraoperative recorded MEPs show no clear relationships. We can conclude that MEPs parameters changes are determined by the surgery procedures during neuromonitoring, not the anesthesia conditions if they are kept stable, which influences a decrease in the number of false-positive neuromonitoring warnings. Further studies on a larger population of patients with long-lasting observation postoperatively are required to confirm the presented conclusions on the direct influences of scoliosis surgery on improvement of the motor function in patients with IS.

Predictive processes and numerous cognitive, motor, and social skills depend heavily on sequence and statistical learning. The visuomotor Serial Reaction Time Task (SRTT) can measure these fundamental cognitive processes. In this review, we sought to answer whether repetitive transcranial magnetic stimulation (rTMS) is suitable for modulating visuomotor sequence learning and which factors mediate its efficacy. We systematically analyzed the eligible records (n = 17) that attempted to modulate the performance of the SRTT with rTMS. The purpose of the analysis was to determine how the following factors affected SRTT performance: (1) stimulated brain areas, (2) rTMS protocols, (3) stimulated hemisphere, (4) timing of the stimulation, (5) SRTT sequence properties, and (6) other methodological features. The primary motor cortex (M1) and the dorsolateral prefrontal cortex (DLPFC) were found to be the most promising stimulation targets. Low-frequency protocols over the M1 usually weaken performance, but the results are less consistent for the DLPFC. These inconsistencies (at least in part) may be due to the current frequency-based heuristics of rTMS effects developed for explaining local stimulation effects in the motor cortex. Although this review cannot provide an ultimate answer about the optimal stimulation and task parameters, it comprehensively discusses the behavioral effects of six factors that are crucial for designing future studies to modulate sequence learning with rTMS. Moreover, we conclude that synergistically combining functional neuroimaging with rTMS could adequately link the rTMS-induced network effects with the behavioral findings that are crucial to develop a unified cognitive model of visuomotor sequence learning.

Objective: to evaluate the effects of excitatory repetitive transcranial magnetic stimulation (rTMS) of the international 10-20 system P3 point (intraparietal sulcus region) in chronic patients with a frontal lesion and parietal sparing due to stroke on the impaired upper (UL) and lower limb (LL) as measured by Fugl-Meyer Assessment (FMA). Methods: three patients (C1: 49.83/2.75, C2: 53.17/3.83, C3: 63.33/3.08 years-old at stroke/ years post-stroke, respectively) received two weeks (five days/ week) of rTMS at 10 Hz of P3. A patient was treated in similar conditions with a sham coil (S1: 56.58/4.33). No complimentary therapy was delivered during the study. Patients were evaluated before, after- and two months post-treatment (A1, A2 and A3, respectively). Results: we found increased scores for LL in motor function subsection for C1 and C3 and in sensory function for C2 by A2 that remained at A3. We also found an increased score for UL motor function for C2 and C3, but the score decreased by A3 for C2. C3 score for UL range of motion increased by A3 compared to A1 and A2. Conclusion: In a variable way, P3 excitatory rTMS increased FMA scores in different upper and lower limb subsections of our three treated patients.

Individual differences in the responsiveness of the brain to transcranial electrical stimulation (tES) is increasingly demonstrated in large variability in the tES effects. Anatomically detailed computational brain models have been developed to address this variability; however, static brain models are not ‘realistic’ in accounting for the dynamic state of the brain. Therefore, human-in-the-loop optimization is proposed in this perspective article based on an extensive systems analysis of the tES neurovascular effects. First, modal analysis was conducted using a physiologically detailed neurovascular model that found stable modes in the 0 Hz to 0.05 Hz range for the pathway for vessel response through the smooth muscle cells, measured with functional near-infrared spectroscopy (fNIRS). tES effects in the 0 Hz to 0.05 Hz range can also be measured with functional magnetic resonance imaging (fMRI)-tDCS data with a maximum TR=10sec. Therefore, we investigated an open-source fMRI-tDCS dataset that used a TR=3.36sec. We found that both the anodal tDCS condition and sham tDCS condition had similar Finite Impulse Response at the region of interest underlying the anode and a remote location, which indicated a global hemodynamic effect of sham tDCS beyond the intended transient sensations. Here, transient sensations can have arousal effects on the hemodynamics so we conducted a healthy case series for black box modeling of fNIRS-pupillometry of short-duration tDCS effects. The block exogeneity test rejected the claim that tDCS is not a 1-step Granger-cause of the fNIRS total hemoglobin changes (HbT) and pupil dilation changes (p<0.05). Also, grey-box modeling using fNIRS of the tDCS effects in chronic stroke showed HbT response to be significantly different (paired-sample t-test, p<0.05) between the ipsilesional and the contralesional hemisphere for primary motor cortex tDCS and cerebellar tDCS which was subserved by the smooth muscle cells. Here, our perspective is that various physiological pathways subserving tES effects can lead to state-trait variability that can be challenging for clinical translation. Therefore, we conducted a case study on human-in-the-loop optimization using our reduced dimension model and a stochastic, derivative-free Covariance Matrix Adaptation Evolution Strategy. Future studies need to investigate human-in-the-loop optimization of tES for reducing inter-subject and intra-subject variability in tES effects.

Objective. To test the hypothesis that a session of unilateral tSMS over the dominant primary motor cortex (M1) in healthy subjects produces a transient decrease in manual dexterity. Methods. A triple-blinded randomized control trial was conducted in 40 healthy participants who were allocated to real- or sham-tSMS group. Each participant underwent one session of tSMS and were assessed before, immediately after, 15 minutes, and 40 minutes after stimulation. Outcome measures were Finger Tapping Test (FTT), 5-seconds FTT, nine Hole Peg Test, and the hand grip assessment. Results: Significant differences were found between groups 15 minutes after stimulation in favor of the tSMS group in the FTT (2.2 ± 0.99; CI= .18-4.22; d= .84p=.034), and 5-second FTT (4.2 ± 1.98; CI= .199-8.2, d= .68; p=.04). In the intragroup analysis, a significantly lower number of taps 15 minutes after stimulation was observed in sham group (3.3 ± 1.01; CI= .47-6.13; d= .42; p=.015), but not in the real stimulation group. Conclusion: A unilateral session of tSMS in the M1 of the dominant hemisphere of healthy individuals does not reduce manual dexterity or grip strength. This technique could have benefits on the motor performance of the arm contralateral to the stimulated motor cortex

The integrated DC-DC converter is appropriate for use in many domains, namely, display, cellular, and portable applications. This paper presents an integrated monolithic voltage-mode DC-DC boost converter with a low-power control circuit. The driver circuit requires an integrated converter to power up a digital logic circuit and converts the unregulated DC input to the controlled DC output at the desired voltage level. It is the integration of both power switches and control circuitry within the same CMOS technology to buck down and boost voltages using a switch mode regulator. In order to increase power efficiency in the DC-DC boost converter that provides low-power operation with a small chip size, a low-voltage operation is applied to the unique circuit characteristic. The operational transconductance amplifier(OTA), comparator, and oscillator in the control circuit are designed with the supply voltage of 3.3V and the operating frequency of 5.5 MHz. A compensator is used to create a pole that has sufficient phase margin for high stability. The DC- DC boost converter is measured in both experiment and simulation. Testing of the proposed circuit on the 0.35μm CMOS process shows that the output transient time of the amplifier can be controlled within of 7μsec and the output voltage is accurately controlled with a ripple ratio of 3%.

Objective: To evaluate the effects of left intraparietal sulcus (IPS) inhibition by repetitive transcranial magnetic stimulation (rTMS) on grip force modulation (GFM) for both hands during a unimanual task. Methods: GFM induced by manual action-verb listening was evaluated for each hand in a unimanual task, and the motor-evoked potentials (MEP) were recorded for both left and right hemispheres prior to and following the left IPS inhibition. Left IPS inhibition was obtained by rTMS (5 min of 1.0 Hz, 60% of maximal stimulator output) of the international 10–20 system P3 point. Seven healthy right-handed subjects were evaluated. Results: One-way repeated measures ANOVA found that MEP amplitude and duration increased following IPS inhibition in the left hemisphere and did not change in the right hemisphere. Language-induced modulation did not change in the left hemisphere, while it was significantly attenuated in the right hemisphere. Since IPS inhibition increased the left primary motor cortex (M1) excitability, the maintenance of language-induced modulation intensity suggests it was also attenuated. Conclusion: Left IPS inhibition increased left M1 excitability without changing right M1 excitability, while attenuating the language-induced GFM for both the left and right hands.

A space charge density wireless measurement system based on the idea of distributed measurement is proposed for collecting and monitoring the space charge density in an ultra-high-voltage direct-current (UHVDC) environment. The proposed system architecture is composed of a number of wireless nodes connected with space charge density sensors and a base station. The space charge density sensor based on atmospheric ion counter method is elaborated and developed, and the ARM microprocessor and Zigbee radio frequency module are applied. The wireless network communication quality and the relationship between energy consumption and transmission distance in the complicated electromagnetic environment is tested. Based on the experimental results, the proposed measurement system demonstrates that it can adapt to the complex electromagnetic environment under the UHVDC transmission lines and can accurately measure the space charge density.

Day by day, the share of renewable energy-based power plants such as offshore wind farms and photovoltaic power plants, in the present-day power systems is escalating. Nevertheless, most of these power-producing facilities have been located quite far away from the load centers. At this stage, HVDC power systems provide satisfactory options due to qualities such as reduced line losses, substantial controllability, and environmental advantages. Nevertheless, unique converter designs are required to combine asynchronous HVDC networks with each other and with already existing high voltage alternating current (HVAC) networks. In this study, based on the above special cases, a unique DC-DC modular multilevel converter (MMC) architecture is presented that provides an excellent solution for both integrating modern asynchronous HVDC networks and integrating these modern HVDC power systems with existing asynchronous HVAC power systems. The mathematical analysis of the recommended DC-DC MMC design has been examined in detail and the power transfer between two asynchronous power grids has been realized in a simulation environment. Efficient bilateral power transmission has been made achievable by the control system. The recommended DC-DC MMC topology has shown to be a highly successful approach, in the interconnection of HVDC power systems, according to the simulation results.

Remote Photoplethysmography (rPPG) has emerged as a non-intrusive and promising physiological sensing capability in HCI research, gradually extending its applications in health-monitoring and clinical care contexts. With advanced machine learning models, recent datasets collected in real-world conditions have gradually enhanced the performance of rPPG methods in recovering heart-rate and heart-rate variability metrics. However, the signal quality of reference ground-truth PPG data in existing datasets is by and large neglected, while poor quality references negatively influence models. Here, this work introduces a new imaging blood volume pulse (iBVP) dataset of synchronized RGB and thermal infrared videos with PPG ground-truth signals from the ear and its high resolution signal quality labels, for the first time. Participants perform rhythmic breathing, head-movement, and stress-inducing tasks, which help reflect real-world variations in psycho-physiological states. This work conducts dense (per sample) signal quality assessment to discard noisy segments of ground-truth and corresponding video frames. We further present a novel end-to-end machine learning framework, iBVPNet that features an efficient and effective spatio-temporal feature aggregation for reliable estimation of BVP signals. Finally, this work examines the feasibility of extracting BVP signals from thermal video frames, which is underexplored. The iBVP dataset and source codes are publicly available for research use.

The widespread adoption of IoT networks has revolutionized modern life thanks to their diverse range of applications. With their increased usage, the need to transfer data securely has never been more vital. Often IoT devices are battery-driven and possess limited processing and storage capabilities. In response to those limitations, there has been a shift towards the implementation of resource-efficient and lighter protocols. This research aims to evaluate how lightweight key establishment through Object Security for Constrained RESTful Environments (OSCORE) and Ephemeral Diffie-Hellman Over COSE (EDHOC) can enhance cybersecurity in IoT networks where resources are limited. The study aims to explore different key management approaches and the effects of certificates on security, efficiency, and power consumption. The research methodology consists of the practical implementation of the protocols in a physical system where factors such as the impact of hardware acceleration on computational overhead and overall power consumption will be assessed. Furthermore, the study will verify the cost of resources and overall efficiency, evaluating them against real-world scenarios. The expected contributions of this study are insights into the tradeoffs between security, power consumption, and efficiency in resource-limited IoT environments.

The main focus of the in vitro toxicity assessment methods is on the viability of the cells, which is usually based on metabolism changes. Yet, when exposed to toxic substances, the cell triggers multiple signals in response. With this in mind, we have developed a promising cell-based toxicity method that observes various cell responses when exposed to toxic substances (either death, division or remaining viable). Based on the collective cell response, we observed and predicted the dynamics of the cell population to determine the toxicity of the toxicant. The method was tested with two different conformations: In the first conformation, we exposed a monoculture model of blood macrophages to UV light, hydrogen peroxide, nutrient deprivation, tetrabromobisphenol A, fatty acids and 5-fluorouracil. In the second, we exposed a coculture liver model consisting of hepatocytes, hepatic stellate cells, Kupffer cells and liver sinusoidal endothelial cells to rifampicin, ibuprofen and 5-fluorouracil. The method showed good accuracy compared to established toxicity assessment methods. In addition, this approach provided more representative information on the toxic effects of the compounds as it considers the different cellular responses induced by toxic agents.

This study builds on our previous Systematic Literature Review (SLR) that assessed the applications and performance of zk-SNARK, zk-STARK, and Bulletproof Non-Interactive Zero-Knowledge Proof (NIZKP) protocols. To address identified research gaps, we designed and implemented a benchmark comparing these three protocols using a dynamic MiMC hash application. We evaluated performance across four general-purpose programming libraries and two programming languages. Our results show that zk-SNARK produced the smallest proofs, while zk-STARK generated the largest. In terms of proof generation and verification times, zk-STARK was the fastest, and Bulletproof the slowest. Interestingly, zk-SNARK proofs verified marginally faster than zk-STARK, contrary to other findings. These insights enhance our understanding of the functionality, security, and performance of NIZKP protocols, providing valuable guidance for selecting the most suitable protocol for specific applications.

Tremor is a prevalent symptom associated with multiple conditions, including Essential Tremor (ET), Parkinson’s disease (PD), multiple sclerosis (MS), stroke, and trauma. The surgical management of tremor evolved from stereotactic lesions to deep-brain stimulation (DBS), which allowed safe and reversible interference with specific neural networks. This paper reviews the current literature on DBS for tremor, starting with a detailed discussion of current tremor targets (Vim, Raprl, caudal Zi, Vo and STN) and continuing with a discussion of results obtained when performing DBS in the various aforementioned tremor syndromes. Future directions for DBS research are then briefly discussed.

Resonance inductive coupling is widely used for wireless power transfer (WPT) in medical applications. In this paper, we analyze the LCL-compensated WPT structure and propose a novel constant voltage transmission system based on gain estimation, without any extra feedback from the receiver. The system is capable for implant neural stimulation where the load impedance and the coupling coefficient are both variable. Compared to existing methods for constant voltage transmission, our approach offers advantages in compact size and the compatibility with the industrial, scientific and medical (ISM) band. We validate the load-independent resonant characteristic and the feasibility of constant voltage transmission using an experimental prototype working at 6.78MHz. Finally, we discuss the structure of the implant stimulator and methods of applying the proposed WPT system.

To investigate the impact of electrode structure on Electrical Stimulation Therapy (EST) for chronic wound healing, this study designed three variants of flexible microelectrodes (FMs) with Ag-Cu coverings (ACCs), each exhibiting distinct geometrical configurations: hexagonal, cross-shaped, and serpentine. These were integrated with PPY@PDA/PANI (3/6) hydrogel dressings. Comprehensive animal studies, coupled with detailed electrical and mechanical modeling and simulations, were conducted to assess their performance. Results indicated that the serpentine-shaped FM outperformed its counterparts in terms of flexibility and safety, exhibiting minimal thermal effects and a reduced risk of burns. Notably, FMs with metal coverings under 3% demonstrated promising potential for optoelectronic self-powering capabilities. Additionally, simulation data highlighted the significant influence of hydrogel non-uniformity on the distribution of electrical properties across the skin surface, providing critical insights for optimizing EST protocols when employing hydrogel dressings.

Repetitive transcranial magnetic stimulation (rTMS) with intensive occupational therapy improves upper limb motor paralysis and activities of daily living after stroke; however, amount of improvement according to paralysis severity remains unverified. Target activities for daily living using patients’ upper limb functions can be established by predicting the amount of change after treatment for each severity level of upper limb motor paralysis and further aid practice planning. This study estimated post-treatment score changes for each severity level of motor paralysis (no, poor, limited, notable, and full) stratified according to Action Research Arm Test (ARAT) scores before combined rTMS and intensive occupational therapy. Severity of motor paralysis was the fixed factor for analysis of covariance, delta (post-pre) of the scores was the dependent variable. Ordinal logistic regression analysis was used to compare changes in ARAT subscores in patients, divided according to paralysis severity before treatment. A multicenter retrospective cohort dataset analyzed 907 patients with stroke hemiplegia. Largest treatment-related changes in scores were observed in the Limited recovery group for upper limb motor paralysis and Full recovery group for quality-of-life activities using paralyzed upper limb. These results will help predict treatment effects and determine exercises and goal movements for occupational therapy after rTMS.

Background/Objectives: The aim of this study was to investigate feasibility and safety of neuromuscular electrical stimulation (NMES) in patients on extracorporeal membrane oxygenation (ECMO) and assess thoroughly any potential adverse events. Methods: We conducted a safety and feasibility study including 16 ICU patients on ECMO support who were admitted to the cardiac surgery ICU from January 2022 to December 2023. Patients underwent a 45-minute NMES session, still on ECMO support, that included a warm up phase of 5 minutes, a main phase of 35 minutes and a recovery phase of 5 minutes. NMES was implemented on vastus lateralis, vastus medialis, gastrocnemius and peroneus longus muscle of both lower extremities. Two stimulators delivered biphasic, symmetric impulses of 75 Hz, with 400 μsec pulse duration, 5 sec on (1,6 sec ramp up and 0,8 sec ramp down) and 21 sec off. The intensity levels aimed to cause visible contractions and be well tolerated. Primary outcomes of the study were feasibility and safety, evaluated by whether the NMES sessions were successfully achieved, and by any adverse events and complications. Secondary outcomes included indices of rhabdomyolysis from biochemical blood test, 24 hours after the application of NMES. Results: All patients successfully completed their 45-minute NMES session, without presenting hemodynamic deterioration, adverse events or signs of rhabdomyolysis. The majority of patients achieved type 4 and 5 quality of muscle contraction. Conclusions: NMES is a safe and feasible exercise methodology in patients supported with ECMO.

Greek roots: "phos" (φῶς) - means "light" and "dynamis" (δύναμις) - means "force" or "power". Photodynamic therapy (PDT) is an innovative treatment method based on the ability of photosensitizers to produce reactive oxygen species after exposure to light of a specific wavelength range, either in the visible or near infrared range. This process results in damage to pathological cells, such as cancer cells, while minimizing the impact on healthy tissues. PDT is a promising direction in the treatment of many diseases, with particular emphasis on the fight against cancer and other diseases asso-ciated with excessive cell growth. The power of light contributed to the creation of phototherapy, whose history dates back to ancient times. It was then noticed that some substances exposed to the sun have a negative effect on the body, while others have a therapeutic effect. This work provides a detailed review of photodynamic therapy, from its origins to the present day. It is surprising how a seemingly simple beam of light can have such a powerful healing effect, which is used not only in dermatology, but also in oncology, surgery, microbiology, virology, and even dentistry. However, despite promising re-sults, photodynamic therapy still faces many challenges. The availability of this thera-py is limited due to the small number of centers offering this type of treatment and the high costs, which may be unaffordable for many patients. Moreover, photodynamic therapy requires further research and improvement.

This research presents a novel algorithmic implementation to improve the analysis of visually controlled interception and accompanying motor action through the computational application of harmonic ratios and stimulation invariants. Unlike traditional models that focus mainly on psychological aspects, our approach integrates the relevant constructs into a practical mathematical framework. This allows for dynamic prediction of interception points with improved accuracy and real-time perception-action capabilities, essential for applications in neurorehabilitation and virtual reality. Our methodology uses stimulation invariants as key parameters within a mathematical model to quantitatively predict and improve interception outcomes. The results demonstrate the superior performance of our algorithms over conventional methods, confirming their potential for ad-vancing robotic vision systems and adaptive virtual environments. By translating complex theo-ries of visual perception into algorithmic solutions, this study provides innovative ways to im-prove motion perception and interactive systems. This study aims to articulate the complex inter-play of geometry, perception, and technology in understanding and utilizing cross-ratios at infin-ity, emphasizing their practical applications in virtual and augmented reality settings.

A novel plasma source of pulsed electrolyte cathode atmospheric pressure discharge (pulsed-ECAD) driven by an alternating current (AC) power supply coupled with a high voltage diode was generated, and the discharge was generated in the open-to-air atmosphere between a metal electrode and a small-sized flowing liquid cathode. The spatial distribution of plasma temperatures (excitation, vibrational and rotational) of the pulsed-ECAD were investigated. The electron excitation temperature of H T_exc(H), vibrational temperature of N₂ T_vib(N₂), and rotational temperature of OH T_rot(OH) were measured as 4900±36-6800±108 K, 4600±86-5800±100 K and 1050±20-1140±10 K, respectively. Meanwhile, the temperature characteristics of dc solution cathode glow discharge (dc-SCGD) were also studied for comparison with pulsed-ECAD. The effects of operating parameters, including discharge voltage and discharge frequency, on the plasma temperatures were investigated. The electron number density determined in the discharge system and dc-SCGD were within the range (3.8–18.9) ×10¹⁴ cm^-3 and 2.6×10¹⁴-17.2×10¹⁴ cm^-3, respectively.

Regeneration of lost tail is of great importance to lizards. Anolis carolinensis, a green lizard, is capable of regenerating its tail efficiently after autotomy. Hence, it is considered as a model organism in regeneration study. A. carolinensis shed its tail in order to distract the predator’s attention and thus makes a way to escape. Restoring of the amputated tail takes several days and the mechanism is currently clearly understood. Although save its life, tail regeneration is associated with the impairment of several vital functions in Anoles. In addition, various differences have been observed between original and regenerated tail in terms of mechanism and structure. To date, very little work has been conducted on tail autotomy and regeneration at molecular and genetic level. The genes responsible for regeneration in anoles are identified recently. These genes are evolutionarily conserved through all tetrapod vertebrates. They are, however, in a state of ‘switched-off’ in other vertebrates including humans. Consequently, a throughout study of these so called ‘switched-off’ genes may provide a way of restoring lost organs in human, and thus could revolutionize the modern medical science.

Small peptides (SPs), ranging from 5 to 100 amino acids, play integral roles in plants due to their diverse functions. Despite their low abundance and small molecular weight, SPs intricately regulate critical aspects of plant life, including cell division, growth, differentiation, flowering, fruiting, maturation, and stress responses. As vital mediators of intercellular signaling, SPs have garnered significant attention in plant biology research. This comprehensive review delves into SPs' structure, classification, and identification, providing a detailed understanding of their significance. Additionally, we summarize recent findings on the biological functions and signaling pathways of prominent SPs that regulate plant growth and development. The review also offers a forward-looking perspective on future research directions in peptide signaling pathways.

Immune checkpoint inhibitors (ICI) are a promising form of immunotherapy that has significantly changed the therapeutic landscape for many advanced cancers. They have shown unique clinical benefit against a broad range of tumour types and a strong overall impact on survival in studied patient populations. However, there are still many limitations holding back this immunotherapy from reaching its full potential as a possible curative option for advanced cancer patients. A great deal of research is being undertaken in the hope of driving advancements in this area, building a better understanding of the mechanisms behind immune checkpoint inhibition and ultimately developing more effective, safer, and wider-reaching agents. Taking into account the current literature on this topic, this review aims to explore in depth the basis of the use of ICIs in the treatment of advanced cancers, evaluate its efficacy and safety, consider its current limitations, and finally reflect on what the future holds for this very promising form of cancer immunotherapy.

After decades of studies, the pathogenesis of Autism Spectrum Disorder (ASD) remains unclear and there still lackseffective treatment strategies for core symptoms. Our recent work, combined with others’ research in a diversity ofmodels and clinical trials, suggested a concise, but potentially rational theory that can illustrate the key of the pathogenesis and treatment of ASD from the aspect of damage control.

Nanomaterials have shown significant promise for enhancing the performance of composite materials and increasing their functionality for various industrial applications. This review explores the unique properties of nanomaterials, particularly carbon-based nanomaterials, and provides key findings in utilizing them to enhance composite performance. It highlights specific nano-based composite materials and their significant potential in advancing the field of nanocomposites. Challenges associated with nanocomposite production and utilization are also discussed, along with possible solutions to address them. Finally, the study provides recommendations for continued research and innovation in nanocomposites to fully unlock the benefits of these advanced materials for broader future applications.

Porous α-Al2O3 ceramics is a highly demanded material for multitude applications such as filters, substrates, biomedicine materials, etc. Despite the availability of the raw materials, a challenge of their technology is in a high energy budget caused by the sintering above 1500 °C. For a cold sintering processing (CSP) of ceramics, the lowering of α-Al2O3 sintering temperature is one of the most urgent challenges at the background of its rapid development. The current paper for the first time demonstrates the solution of the mentioned problem by the CSP of α-alumina ceramics in a presence of pure water as a transient liquid. The manufactured materials were examined by XRD analysis; the evolution of their microstructures during the CSP was revealed by SEM, and the porosity evaluated by the Archimedes method. The ceramics with an open porosity up to 36 % was produced at 380-450 °C, 220 MPa in 30 min. An increase in the pressure was found to impede α-Al2O3 formation from γ-AlOOH. The development of the microstructure was discussed within the frameworks of the dissolution-precipitation model and the homogenous nucleation. The results of the SEM study pointed to the coalescence of γ-AlOOH grains during the CSP.

The results of experimental studies of ohmic conductivity degradation in the ensembles of nanostructured anatase bridges under long-term effect of direct current are presented. Stochastic sets of interelectrode partially conducting bridges consisting of close-packed anatase nanoparticles were formed by the seeding particles from drying aqueous suspensions on the surfaces of silica substrates with interdigital platinum electrodes. Multiple-run experiments at room temperature have shown that ohmic conductivity degradation in these systems is irreversible. It is presumably due to accumulated capture of conduction electrons by deep traps in anatase nanoparticles. The scaling analysis of voltage drops across the samples at the final stage of degradation gives a critical exponent for ohmic conductivity as 1.597. This value satisfactorily agrees with the reported model data for percolation systems. At an early stage of degradation, the spectral density of conduction current fluctuations wihin the frequency range of 0.01 Hz - 1 Hz decreases approximately as , while near the percolation threshold the decrease trend changes to . This transition is interpreted in terms of an increasing contribution of blockages and subsequent avalanche-like breakdowns of part of the local conduction channels in the bridges into electron transport near the percolation threshold.

To clarify the risk factors for aggravation of esophagogastric varices (EGV) after hepatitis C virus (HCV) eradication with direct-acting antiviral (DAA) therapy, we enrolled 167 consecutive patients with HCV-related compensated cirrhosis who achieved a sustained virological response (SVR) after DAA therapy. During a median of 69 months, EGV was aggravated in 42 (25%) patients despite SVR. The cumulative 1, 3, 5, and 10-year aggravated EGV rates were 7%, 23%, 25%, and 27%, respectively. Multivariate analysis identified platelet count <11.0×10⁴/μL, LSM ≥18.0 kPa, total bile acid ≥33.0 μmol/L, and diameter of left gastric vein (LGV) ≥5.0 mm at HCV eradication as independent risk factors for EGV aggravation post-SVR. In groups that meet all of these risks, the cumulative EGV aggravation rates at 1, 3, and 5 years were 27%, 87%, and 91%, respectively. However, none of the patients who had only one or none of the risk factors experienced EGV aggravation. Platelet count, LSM, total bile acid, and diameter of LGV at HCV eradication were associated with aggravated EGV post-SVR. EGV tends to worsen as two or more of these risk factors increase.

Cell viability refers to the proportion of living, healthy cells within a given population. This information is crucial in any cell-based research, especially in toxicology. Over the past century, numerous methods for assessing cell viability have been developed. These methods can be categorized into five main types: non-invasive cell structure damage, invasive cell structure damage, cell growth, cellular metabolism, and cell membrane potential. Each method operates on different principles and has its own advantages and disadvantages, making it essential for researchers to choose the method that best fits their experimental design. Despite the variety of cell viability methods available, most rely on indirect measurements of cell viability, which may compromise their accuracy. In this sense, there is insufficient information regarding their accuracy, highlighting the need for researchers to investigate the accuracy of both existing and future methods.

Very heavy stratiform precipitation (> 200 mm/per day) occurred in the Hokitika region on the west coast of the South Island of New Zealand on 18 June 2015, under north-westerlies with small CAPE (< 25 J/kg). Analyses of model simulations and observations showed that this heavy rainfall was due to cold front lifting enhanced by orographic lifting over the Southern Alps. At 1.5 km grid-length, the model terrain underestimated the average height of the 103 tallest mountains over the South Island by ~ 800 m. This leads to weaker orographic lifting and mountain blocking, and a faster-moving and stronger cold front in the Hokitika region. As a result, large errors in the heavy rainfall prediction occur. By increasing either the resolved or the sub-grid mountain heights, the simulated rainfall errors were largely reduced through stronger orographic lifting and mountain blocking, and a better simulation of the cold front movement and strength. All the experiments have the same “flow-over” regime with mountain waves and/or wave breaking (Fm ranges 0.61 – 1.21). However, the rainfall amount and distribution on the windward side of mountains altered significantly. Our new findings were that the Southern Alps can have significant indirect effects on heavy rainfall by altering the speed and strength of the cold front, in addition to the well-known direct dynamical effects (i.e., orographic lifting and mountain blocking). A combination of these direct and indirect effects makes the heavy rainfall simulation sensitive to mountain heights even under the same “flow-over” regime.

BACKGROUNDBrain death in most countries requires supplementation of clinical diagnosis with ancillary tests such as EEG, cerebral angiography, or radionuclide imaging. Transcranial Doppler sonography (TCD) is one such non-invasive, real-time, bedside test that sidesteps the logistic hurdles associated with some of the tests mentioned above. OBJECTIVETo substantiate the utility of TCD as a reliable ancillary test to diagnose brain death with more certainty and reliability.METHODOLOGYMeta-analysis was performed with the use of statistical and analytical software to obtain data and estimate Sensitivity, Specificity, positive predictive value(PPV), diagnostic odds ratio (DOR), and relative risk with 95 percent confidence intervals to examine critical clinical outcomes(CI).RESULTSInitial dataset of 31 studies of which 16 studies, with a total of 1317 patients was used considering the reliability of the data. The pooled sensitivity and specificity of TCD were 0.91 (95% CI range: 0.89-0.93) and 0.99 (95% CI range: 0.97-0.99) respectively. The summary of the ROC curve showed an area under the curve of 0.9750 and an overall diagnostic odds ratio (DOR) was 323.26 with the Younden Index being 0.9. Summary of Fagan plot analysis of all studies showed a prior probability of 63% (1.7); a Positive Likelihood Ratio of 56, a post-test probability of 99% (96); a Negative likelihood ratio of 0.09, and a post-test probability of 13% (0.2).CONCLUSIONOur study emphasizes that clinical diagnosis is sufficiently adequate to declare a patient cerebrally dead. However, for ambiguous cases, TCD is a practical and fast method showing close correspondence to angiography and is superior to other bedside tests like EEG.

Neurologic disorders such as traumatic brain injury, multiple sclerosis, Alzheimer’s disease, and drug-resistant epilepsy have a high socioeconomic impact around the world. Current therapies for these disorders are often not effective. This creates a demand for the development of new therapeutic approaches to treat these disorders. Recent data suggest that autoreactive naturally occurring immunoglobulins produced by subsets of B cells called B1 B cells combined with complement are actively involved in the processes of restoration of neuronal functions during pathological conditions and remyelination. The focus of this review is to discuss the possibility of creating specific therapeutic antibodies that can activate and fix complement to enhance neuronal survival and promote central nervous system repair after injuries associated with many types of neurodegenerative diseases.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder characterized by the development and progression of multiple renal cysts, leading to progressive renal function decline. To date, the only approved treatment for this condition is able to slow down the loss of annual renal function, without stopping the disease progression. Furthermore, this therapy is approved only for patients with rapid disease progression and its compliance is problematic because of the impact of this drug on quality of life. The recent literature suggests that cystic cells are subject to metabolic dysregulation in the glucose pathway (Warburg Effect). This finding paved the way for new lines of research targeting potential therapeutic interventions for ADPKD. In particular, this review highlights the latest studies on the use of ketosis, through ketogenic dietary interventions (daily calorie restriction, intermittent fasting, time-restricted feeding, and ketogenic diets), as a potential strategy for patients with ADPKD, and the possible involvement of microbiota in the ketogenic interventions’ effect.

Digital gait monitoring is increasingly used to assess locomotion and fall risk. The aim of this work is analyzing the changes in the foot-floor contact sequences of Parkinson’s Disease (PD) patients in the year following the implant for deep brain stimulation (DBS). During their best-ON condition, 30 PD patients underwent gait analysis at baseline (T0), at 3 months (T1), and 12 months (T2) after the DBS neurosurgery for bilateral high-frequency subthalamic nucleus stimulation. Thirty age-matched controls underwent gait analysis once. Each subject was equipped with bilateral foot-switches and a 5-minute walk was recorded, including both straight-line and turnings. The walking speed, turning time, stride time variability, percentage of atypical gait cycles, stance, swing, and double support duration were estimated. Overall, the gait performance of PD patients improved after DBS, as also confirmed by the decrease in the UPDRS-III score from 19.4±1.8 to 10.2±1.0 points (T0 vs. T2) (p < 0.001). In particular, the percentage change of atypical gait cycles of PD more affected side decreased at T1 (Straigh-line: -72%; Turnings: -43%) and at T2 (Straigh-line: -54%; Turnings: -20%). The percentage of atypical gait cycles proved an informative digital biomarker for quantifying PD gait changes after DBS, both in straight-line paths and turnings.

As the number of end-of-life vehicles continues to grow, the field of separation technology for broken copper and aluminium parts of end-of-life vehicles has emerged as a significant area of research. As a key technology for the separation of non-magnetic non-ferrous metals, such as copper and aluminium, eddy current separation can achieve efficient separation of non-magnetic non-ferrous metals according to their differing conductivity and density. Nevertheless, further research is required in the separation of large-scale broken copper and aluminium parts of end-of-life vehicles. This paper presents a novel magnetic roller model comprising circumferential and axial periodic arrangements of permanent magnets. A single permanent magnet was constructed as an equivalent current model, and the magnetic scalar potential equations were solved using simulation tools. This allowed the distribution of the magnetic field outside the magnetic roller to be studied. The results demonstrate that the novel permanent magnet array magnetic roller can enhance the magnetic field intensity and action distance of the external magnetic field, which is more conducive to the separation of large-scale broken copper and aluminium parts of scrap cars. The findings of this research provide a theoretical foundation for the separation of scrap car broken copper and aluminium parts.

In the field of railroad safety, effective detection of surface cracks is critical, necessitating reliable, high-speed non-destructive testing (NDT) methods. This study introduces a hybrid Eddy Current Testing (ECT) probe, specifically engineered for railroad inspection, to address the common issue of ’lift-off noise’ due to varying distances between the probe and test material. Unlike traditional ECT methods, this probe integrates transmit and differential receiver coils, aiming to enhance detection sensitivity and minimize lift-off impact. The study optimizes ECT probes employing different driver coils, emphasizing three main objectives: a) quantitatively evaluating each probe using signal- to-noise ratio (SNR) and outlining a real-time data processing algorithm based on SNR methodology; b) exploring the frequency range proximal to the electrical resonance of the receiver coil; c) examining sensitivity variations across varying lift-off distances. The experimental outcomes indicate that the newly designed probe with figure 8-shape driver coil significantly improves sensitivity in detecting surface cracks on railroads. It achieves an impressive SNR exceeding 100 for defects with minimal dimensions of 1 mm in width and depth. Simulation results closely align with experimental findings, validating the investigation of optimal operational frequency and lift-off distance for selected probe performance, determined to be 0.3 MHz and 0.5 mm, respectively. The realization of this project would lead to notable advancements in enhancing railroad safety by improving crack detection efficiency.

In individuals with spinal cord injury (SCI), rapid skeletal muscle atrophy and metabolic dysfunction pose profound rehabilitation challenges, often resulting in substantial loss of muscle mass and function. This study evaluates the effect of combined neuromuscular electrical stimulation (Comb-NMES) on skeletal muscle cross-sectional area (CSA) and inflammatory signaling within the acute phase of SCI. We applied a novel Comb-NMES regimen, integrating both high-frequency resistance and low-frequency aerobic protocols on the vastus lateralis muscle, to participants early post-SCI. Muscle biopsies were analyzed for CSA and inflammatory markers pre-and post-intervention. The results revealed a preservation of muscle CSA in the Comb-NMES group compared to a control group receiving transcutaneous electrical nerve stimulation and passive movements. Inflammatory signaling proteins such as TLR4 and Atrogin-1 were downregulated, whereas markers associated with muscle repair and growth were modulated beneficially in the Comb-NMES group. The study's findings suggest that early application of Comb-NMES post-SCI can attenuate inflammatory pathways linked to muscle atrophy and potentially promote muscle repair, advocating for its inclusion in early rehabilitation efforts. However, the small sample size and variability in injury characteristics emphasize the need for further research to corroborate these results across a more diverse and extensive SCI population.

Air pollution has become one of the biggest problems throughout the world. Smog has a severe effect on the pulmonary and circulatory systems, which causes a significant number of deaths globally. Therefore, the remediation of air pollutants to maintain ecosystem processes and functions and to improve human health is a crucial problem confronting mankind today. This review aims to discuss the health effects of smog on humans. This review will also focus on the bioremediation of air pollution (smog) using bacteria, fungi, phytoremediation, nanotechnology, and phylloremediation (using plants and microbes). Phyllo-remediation is the most effective technology for removing air pollution naturally. The future perspective presents a great need to produce an ecosystem where microbes, plants, and nanoparticles synergistically control smog. In addition, further advancements would be needed to modify the genetic makeup of microbes and plants. Biotechnological approaches like CRISPR-Cas9 can be applied to the editing and cutting specific genes responsible for the bioremediation of VOCs, NOx, SOx, and harmful hydrocarbons. The extracted genes can then be expressed in biologically modified microorganisms and plants for enhanced bioremediation of smog.

China’s greenhouse industry has thousands of years of development history, although the development of modern greenhouses has come late. After decades of development of China, its greenhouse industry is in the forefront of the world. China’s greenhouse industry is experiencing rapid development, transformation and upgrading. China ranks first in the world in terms of greenhouse area, used mainly for vegetable cultivation and plays an important role in the utilization of agricultural resources and food production. In 2023, the cumulative area of new greenhouses nationwide was 1835.87 million ha. In this paper we present the latest developments in the greenhouse sector. More specifically, we present a greenhouse market development overview, the greenhouse production, the greenhouse industry, and technology development. Current problems are underpinned, development opportunities and prospects are analyzed, and measures and specific proposals are detailed for the technological development of the greenhouse sector both for increasing product quantity and quality.

Several studies report an impact of the neurotransmitter dopamine (DA) on human immune cells, with effects dependent on immune cell type addressed and their activation status. Another contributing factor appears to be sex, as sex-specific differences in the dopaminergic pathway are described in the neurological context as well as in autoimmune diseases. However, a deeper understanding of these differences in peripheral immune cells remains limited. In this study, we investigated the effects of dopaminergic stimulation on activation and cytokine secretion of peripheral blood mononuclear cells from women and men using flow cytometry, ELISA and multiplex assay. We found a B cell-driven downregulation in cytokine secretion of monocytes exclusively from women under physiological conditions. Moreover, B cells from men showed higher dopamine receptor (DR) expression, which was shown to be further increased by sex hormones only in men. In monocytes from women, an acute inflammatory stimulus via CpG combined with dopaminergic stimulation caused a switch to a proinflammatory phenotype, which was less pronounced in men. These novel findings in sex-specific responses to dopaminergic stimulation are crucial for understanding DA’s function in the healthy and activated immune system and provide evidence to treat DA-related pathologies in a sex-specific manner.

In this work, non-ordered and ordered CeO2-based catalysts are proposed for the CO2 conversion to dimethyl carbonate (DMC). Particularly, a non-ordered mesoporous CeO2, consisting of small nanoparticles of about 8 nm, is compared with two highly porous (635-722 m2/g) ordered CeO2@SBA-15 nanocomposites obtained by two different impregnation strategies (a two-solvent impregnation (TS) and a self-combustion (SC) method), with a final CeO2 loading of 10 wt%. The Rietveld analyses on XRD data combined with TEM imaging evidence the influence of the impregnation strategy on the dispersion of the active phase: nanoparticles of 8 nm for the TS composite vs. 3 nm for the SC composite. The catalytic results show comparable activity for the mesoporous ceria and the CeO2@SBA-15_SC nanocomposite, while a lower DMC yield was found for the CeO2@SBA-15_TS nanocomposite. This finding is presumably ascribed to a partial obstruction of the pores by the CeO2 nanoparticles in the case of the TS composite, which leads to a reduced accessibility of the active phase. On the other hand, in the case of the SC composite, where the CeO2 particle size is much lower than the pore size, there is an improved accessibility of the active phase to the molecules of the reactants.

This work presents a novel compact CMOS potentiostat designed circuit for electrochemical cell. The proposed topology functions as a circuit interface, controlling the polarization of voltage signals at the sensor electrodes and facilitating current measurement during the oxidation-reduction process of a analyzed solution. The potentiostat, designed for CMOS technology, comprises a two-stage amplifier, two current mirror blocks coupled to this amplifier, and a CMOS push-pull output stage. It employs the electrochemical method of cyclic voltammetry, operating within voltage range of ±0.8 V and scan rates of 10mV/s, 25mV/s, 100mV/s and 250 mV/s. The circuit is capable of reading currents ranging from 10 µA to 500 µA. Experimental results were obtained using a potassium ferrocyanide (K3(FeCN)6) redox solution with concentrations of 10, 15 and 20 mmol/L, and their corresponding voltammograms were evaluated. The experimental results from a discrete circuit demonstrate that the proposed potentiostat topology produces outcomes consistent with those of classical topologies presented in the literature and industrial equipment.

In the field of quality control, the critical challenge of analyzing microdefects in steel filament holds significant importance. This is particularly vital as steel filaments serve as reinforced fibers in the use and applications within various component manufacturing industries. This paper addresses the crucial requirement of identifying and investigating microdefects on steel filaments. Eddy current signals are used for the identification of microdefects, and an in-depth investigation is conducted. The core objective is to establish the relationship between the depth of defects and the signals detected through the eddy current sensing principle. The threshold of eddy current instrument was set at 10%, corresponding to a created depth of 20 µm, to identify defective specimens. A total of 30 defective samples were analyzed, and the phase angles between the experimental and theoretical results were compared. The depths of defects ranged from 20 to 60 µm, with one sample having a depth exceeding 75 µm. The calculated threshold of 10.18% closely aligns with the set threshold of 10%, with a difference of only 1.77%. The resulting root mean square error (RMSE) was found to be 10.53 degrees, equivalent to 3.49 µm for the difference in depth and phase between measured results and estimated results. This underscores the methodology's accuracy and its applicability across diverse manufacturing industries.

The rapid advancement of large language models (LLMs), such as ChatGPT, has revolutionized natural language processing, enabling these models to generate coherent and contextually relevant text. These capabilities hold significant potential for various applications, particularly in the medical field. LLMs can assist healthcare professionals by providing accurate information, supporting diagnostic processes, and enhancing medical education. However, the implementation of LLMs in clinical settings faces several barriers, including technical limitations, ethical concerns, regulatory constraints, and practical challenges. Ensuring accuracy, reliability, and interpretability is crucial, along with addressing biases, ensuring data privacy, and establishing ethical guidelines. Future research should focus on improving training techniques, developing explainable AI methods, and creating efficient, resource-saving models. Expanding applications through domain-specific models and multi-modal integration can further unlock the potential of LLMs. By addressing these challenges and prioritizing responsible development, LLM technology can be safely and effectively integrated into various domains, driving innovation and improving outcomes. This paper explores the current state of LLM technology, its medical applications, barriers to implementation, and directions for future research and development

Smart electronic devices and telemedicine are widely used in humans' daily lives. This provides remote treatment of patients using information and communications technology. New telemedicine technologies, such as the Internet of Medical Things (IoMT), make it easier for medical and computing devices to communicate regularly and effectively. Critical motivations for adapting the IoMT are reduced cost, increased quality of life, and timely medical intervention. IoMT is significant because it enables continuous, real-time patient monitoring during routine everyday activities using a variety of wearables and sensors. With big data, the IoMT technology makes excellent use of Artificial Intelligence (AI) to support disease detection and health condition prediction, alerting patients and healthcare providers. Many research studies have been conducted to explore various aspects of IoMT and its applications in the real world. However, it is challenging to comprehend all the techniques and solutions proposed by the research community. Therefore, this survey sheds light on some crucial aspects of IoMT technologies and explores the potential research gaps and directions the research community could tackle. The survey examines and discusses the characteristics of IoMT standards, protocols, and types. It then delves into the layers of IoMT and distinguishes them into Fog and edge. The studies published under each type were explored, and the limitations of these works were highlighted. The research gaps and directions on IoMT approaches and technologies were also highlighted. With such findings and research directions, further research endeavors could be carried out to address the issues and existing limitations in the IoMT.

Extracellular electron transfer (EET) is key to the success of microbial fuel cells (MFCs). Clostridium sp. often occurs in MFC anode communities, but its ability to perform EET remains controversial. We have employed Clostridium pasteurianum DSM 525 as biocatalyst in a glycerol-fed MFC, designated MFC_DSM. We have also followed the EET of this biocatalyst in the presence of a mediator, namely soluble neutral red (NR), soluble methyl viologen (MV), neutral red film (FNR), or methyl viologen film (FMV). MFC_DSM provided power and current densities (j) of 0.39 mW.cm^-2 and 2.47 mA.cm^-2, respectively, which evidenced that the biocatalyst performs direct electron transfer (DET). Introducing 150.0 µM NR or MV into the MFC_DSM improved the current density by 7.0- and 3.7-fold (17.05 and 8.45 mA.cm^-2), respectively. After 20 cyclic voltammetry (CV) cycles, the presence of FNR in the MFC_DSM anodic chamber provided almost twofold higher current density (30.76 µA.cm^-2) compared the presence of NR in the MFC_DSM. Introducing MV or FMV into the MFC_DSM anodic chamber gave practically the same current density after 10 CV cycles. The MFC_DSM anodic electrode might interact with FMV weakly than with FNR, so FNR is more promising to enhance C. pasteurianum DSM 525 EET within MFC_DSM.

Among natural disasters, earthquakes have a considerable impact and are among the ten deadliest, with an extreme impact on the healthcare sector. This study aimed to analyze best practices in nursing care for earthquake victims. An in-depth analysis was carried out by using a scoping review, a method used in accordance with the PRISMA-ScR recommendations to identify best nursing practice in these circumstances based on searches of eight databases: MEDLINE via PubMed; Cochrane Library; Embase; VHL; PDQ-Evidence; Scopus; ProQuest; Google Scholar. Twenty-one studies were selected. The nursing practices identified were grouped into two distinct dimensions, each subdivided into four subcategories: (i) care practices: a) immediate care, b) intermediate care, psychosocial care and d) ethical care; (ii) care management and coordination practices, which cover (a) care coordination, (b) victim care network organization, (c) teamwork and (d) training. By analyzing these nursing practices during care and relief operations for earthquake victims, this study identified the various actions carried out, the nursing skills to be developed and the reinforcement of these advanced practices through the systematization of nurses’ skills, in order to promote victims’ rehabilitation, minimize their suffering and improving their quality of life during and after an earthquake.

Abstract: High step-up voltage gain nonisolated DC-DC converter have attracted much attention in photovoltaic, fuel cells and other renewable energy system applications. In this paper, by combining input current ripple-free boost cell with coupled-inductor voltage-doubler cell, an input current ripple-free high voltage gain nonisolated converter is proposed. In addition, passive lossless clamp circuit is adopted to recycle the leakage inductor energy and to reduce the voltage spike across the power switch. By utilizing voltage-doubler cell consisting of diode and capacitor, the voltage stress of switch is further reduced and the resonance between the leakage inductor and the stray capacitor of the output diode is eliminated. A low switch-on-resistance low-voltage-rated MOSFET can therefore be employed to reduce the conduction loss and cost. The reverse recovery loss of output diode is reduced, and the efficiency of converter can be improved. Furthermore, the proposed converter can achieve nearly zero input current-ripple and make the design of electromagnetic interference (EMI) filter easy. Steady state analysis and operation mode of the converter is performed. Finally, experimental results are presented to verify the analysis results of the proposed converter.

Automatic and blind parameter estimation based on the inherent features of wireless signals is a major research area due to the fact that these techniques lead to the simplification of receivers, especially in terms of coarse synchronization, more importantly reduce down the signaling load at the control channels. Thus, in the literature many techniques are proposed to estimate a vast set of parameters including modulation types and orders, data and chip rates, phase and frequency offsets and so on. In this paper, a cyclostationary feature detection based method is proposed to estimate the carrier numbers and carrier spacing of carrier-aggregated direct sequence spread spectrum cellular signals blindly. The particular chip rate of the signal is also estimated through the process jointly. In the paper, after the proposed method is formulated, the measurement setup which is developed to collect the data for the validation of the proposed method is introduced. The measurement results are post-processed for performance analysis purposes. To that end, the method is investigated in terms of SNR values, different channel conditions, and measurement durations. Furthermore, the performance of the proposed method is compared with that of energy detection. Measurement results indicate superior performance of the proposed method under significant wireless channel impairments and in low-SNR regions.

Background and Aims: Sustained virologic response (SVR) lead to the decrease of portal hypertension, the regression of fibrosis, the improvement of the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in HCV cirrhotic patients treated with DAAs. Methods: We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological and coagulation tests were collected at baseline, EOT and SVR12/24. Results: We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), the degree of severity of cirrhosis placed the patients mainly in Child-Pugh classes B (40%) and C (36%). All patients achieved SVR. The MELD score decrease at EOT (13.48 ± 4.273; p =0.001), and SVR (9.88 ± 2.774; p = 0.000), compared to baseline (14.92 ± 4.707). Fibroscan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT) there was a trend towards improvement during treatment, changes that were statistically significant for the majority of patients. Factor II low at baseline (75.40 ± 7.506), increases at EOT (87.40 ± 9.587), and later at SVR (99.12 ± 11.695; p = 0.000). FVIII values increased at baseline (175.52 ± 16.414) decrease at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). FvW values decreased during treatment (146.84 ± 9.428 – baseline, 141.32 ± 9.690; p =0.000 – EOT, 126.68 ± 17.960 – SVR). In regards to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at baseline and in Child-Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions: Our study proved that the “reset” of the coagulopathy might be due to the improving of the liver function due to viral eradication secondary to AAD therapy.

Embryo’s Implantation is a question that we are not in the position to answer in full details. We know that it depends on embryo’s quality and uterine receptivity. It is possible to access uterine cavity before in vitro fertilisation by a variety of tools, however hysteroscopy is the gold standard in evaluation of uterine cavity and potential pathology. The frequencies of unrecognised uterine pathology revealed by hysteroscopy are 18-50% and 40-43% in patients undergoing in vitro fertilisation or after recurrent implantation failure respectively. Data is inconclusive regarding the role of hysteroscopy on pregnancy outcome after in vitro fertilisation. This review aims to evaluate the validity of office hysteroscopy in subfertile population before or after IVF treatment

Background: Aging impacts semantic abilities, therefore semantic exercises might be a valuable tool for cognitive stimulation in healthy older adults. However, programs in this area are limited. Methods: In the current paper, we adapted the BOX linguistic semantic program for online use via the CerUp platform. Our goal was to prepare the optimization future experience of CerUp users, including potential changes in task structure, level of difficulty and instructions, and participants’ adherence, engagement, performance accuracy, perceived difficulty, and adequacy ratings assigned to the instructions we provided that might guide future changes. Additionally, we created a map of hypothesized task-specific features that may guide tailor-made uses of the program. Results: To that end, we present preliminary results on the usability of CerUp. By analyzing task-specific usability data alongside the hypothesized map of task-specific features, we also tested the validity of the latter. Conclusions: These preliminary results on the usability of the CerUp platform highlight the potential of programs for semantic stimulation. Such findings can inform future optimizations of the program, tailored to users’ needs and effectively supporting overall language skills and general cognition.

Non-toroidal shape primary pass through protection current transformers (CTs) are used to measure high currents. Their design provides them with a big airgap that allow passing several cables per phase though them, which is the main advantage versus toroidal types, as the number of CTs required to measure the whole phase current is drastically reduced. The cables pass through the transformer window can be in several positions. As the isolines of the magnetic field generated by the primary currents are centered in the cables, if these cables are not centered in the transformer window, the magnetic field will be non-uniform along the transformer core. Consequently, local saturations can appear if the cables are not properly disposed causing the malfunction of the CT. In this paper, the performance of a non-toroidal shape protection CT is studied. The research is focused on the cable position influence in possible partial saturations of the CT when it is operating near to its accuracy limit. Depending on the cable position, the ratio of the primary and secondary currents can depart from assigned ratio. The validation of this phenomenon has been carried out via Finite Element Analysis (FEA) showing that partial transformer core saturations appears in areas of the magnetic core close to the cable. Applying FEA, also the admissible accuracy region for cable positioning inside the CT is delimited. Finally, the simulation results are ratified with experimental tests performed in non-toroidal protection CTs varying the primary cables’ positions, which are subjected to currents up to 5 kA, achieving satisfactory results. From this analysis, installation recommendations are given.

Thyroid surgery rates have tripled over the past 3 decades making it one of the most frequently performed procedures within general surgery. They are associated with the possibility of serious postoperative complications having a significant impact on the patient's quality of life. The recurrent laryngeal nerve (RLN) palsy and the external branch of the superior laryngeal nerve (EBSLN) palsy are, next to hypoparathyroidism and bleeding after operation, one of the most common complications. The introduction of neuromonitoring into thyroid surgery, enabling both confirmation of anatomical integrity and assessment of laryngeal nerve function, was a milestone that has begun a new era in thyroid surgery. The International Neural Monitoring Study Group made standardization of the technique of RLN and EBSLN monitoring during thyroid and parathyroid surgery which increased prevalence of neural monitoring during thyroidectomy. Current status of IONM and benefits of its use have been presented in this publication.

Recent advancements in brain stimulation and nanomedicine have ushered in a new era of therapeutic interventions for psychiatric and neurodegenerative disorders. This review explores the cutting-edge innovations in brain stimulation techniques, including their applications in alleviating symptoms of main neurodegenerative disorders and addiction. Emphasis is placed on the underlying main neurotransmitter modifications and their specific brain area location, particularly focusing on the dopaminergic system, which plays a critical role in these conditions. Furthermore, the review delves into the groundbreaking developments in nanomedicine, highlighting how nanotechnology can be utilized to target aberrant signaling in neurodegenerative diseases, with a specific focus on the dopaminergic system. The discussion extends to emerging technologies such as magnetoelectric nanoparticles (MENPs), which represent a novel intersection between nanoformulation and brain stimulation approaches. These innovative technologies offer promising avenues for enhancing the precision and effectiveness of treatments by enabling non-invasive, targeted delivery of therapeutic agents as well as on site, on-demand stimulation. By integrating insights from recent research and technological advances, this review aims to provide a comprehensive understanding of how brain stimulation and nanomedicine can be synergistically applied to address complex neuropsychiatric and neurodegenerative disorders, paving the way for future therapeutic strategies.

As the penetration of renewable energies increases, their acceptance of the power grid system is becoming an important issue. In the case of South Korea, a 22.9kV transformer is frequently utilized to reduce the power loss of the generated renewable energy transmission, so the power quality at the point of common connection (PCC) is inevitably influenced by the nonlinearity of the transformer and the uncertainty of the inductance and resistance of the transmission line. In this paper, we present a point of common connection voltage-modulated direct power control (PCCVM-DPC) system that enhances power quality at the PCC. First, we present the mathematical dynamics of active and reactive power at the PCC side, which contains the step-up transformer’s nonlinearity, the grid voltage harmonics, and the parameter uncertainties. By analyzing the disturbance terms of the PCCVM-DPC system, we present the disturbance observer (DOB) for the PCCVM-DPC system. To assess the efficacy of our approach, we perform comparative studies of the PCCVM-DPC without DOB and PCCVM-DPC with DOB by constructing the simulation environment based on the commercial step-up transformer and ESS inverter datasheet. We have validated that the active and reactive power control performance of the PCCVM-DPC with DOB outperforms the PCCVM-DPC without DOB from the observation that the current total harmonic distortion reduced by more than 40% compared to the PCCVM-DPC without the DOB.

Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric alpha-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with alpha-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused bundling of actin filaments in the absence of alpha-actinin and enhanced alpha-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to alpha-actinin via its globular ends. The interaction between alpha-actinin and SYNPO2La stabilized the two proteins on actin filaments. These results strongly suggest that SYNPO2L cooperates with alpha-actinin during actin bundle formation to facilitate sarcomere formation and maintenance.

The agonist-antagonist myoneural interface (AMI), a surgical method to reinnervate physiologically-relevant proprioceptive feedback for control of limb prostheses, has demonstrated the ability to provide natural afferent sensations for limb amputees when actuating their prostheses. Following an AMI surgery, one potential challenge is atrophy of the disused muscles, which would weaken the reinnervation efficacy of AMI. It is well known that electrical muscle stimulus (EMS) can reduce the muscle atrophy. In this study, we conducted an animal investigation to explore whether the EMS can significantly improve the electrophysiological performance of AMI. The AMI surgery was performed in 14 rats, in which the distal tendons of bilateral solei donors were connected and positioned on the surface of the left biceps femoris. Subsequently, the left tibial nerve and the common peroneus nerve were sutured onto the ends of the connected donor solei. Two stimulation electrodes were affixed onto the ends of the donor solei for EMS delivery. The AMI rats were randomly divided into two groups. One group regularly received the EMS treatment (designated as EMS_on) for eight weeks and another was no EMS (designated as EMS_off). Two physiological parameters, nerve conduction velocity (NCV) and motor unit number, were derived from the electrically evoked compound action potential (CAP) signals to assess the electrophysiological performance of AMI. Our experimental results demonstrated that the reinnervated muscles of the EMS_on group generated higher CAP signals in comparison to the EMS_off group. Both NCV and motor unit number were significantly elevated in the EMS_on group. Moreover, the EMS_on group displayed statistically higher CAP signals on the indirectly activated proprioceptive afferents than the EMS_off group. These findings may suggested that the EMS treatment would be promise in enhancing the electrophysiological performance and facilitating the reinnervation process of AMI.

Despite improvements in participation in population-based screening programs, colorectal cancer remains a major cause of cancer-related mortality worldwide. Targeted interventions are desirable to reduce the health and economic burden of this disease. Two-dimensional monolayers of colorectal cancer cell lines represent the traditional in vitro models for disease and are often used for diverse purposes, including delineation of molecular pathways associated with disease aetiology or to gauge drug efficacy. The lack of complexity in such models, chiefly the limited epithelial cell diversity and differentiation, attenuated mucus production, lack of microbial interactions and mechanical stresses, has driven interest in development of more holistic and physiologically relevant in vitro model systems. In particular, established ex vivo patient-derived explant and patient-derived tumour xenograft models have been supplemented by progress in organoid and microfluidic organ-on-a-chip cultures. Here we discuss the applicability of advanced culturing technologies, such as organoid systems, as models for colorectal cancer and for testing chemotherapeutic drug sensitivity and efficacy. We highlight current challenges associated with organoid technologies and discuss their future for more accurate disease modelling and personalized medicine.

Dogs and cats have become the most influential and successful pets through long-term domestication. People keep them for various reasons, such as their functional roles or for physical or psychological support. However, why humans are so attached to dogs and cats remains unclear. A comprehensive understanding of the current state of human preferences for dogs and cats and the potential influential factors behind it is required. Here, we investigate this question using two independent online datasets and anonymous questionnaires. We find that current human preferences for dogs and cats are relatively higher than for most other interests, such as games and music. Genetic variations, gender, age, and economic development levels notably influence these preferences for dogs and cats. Specifically, dog and cat ownership is significantly heritable (h2 = 0.43, 95%CI: 0.35 -0.51) and further analysis found that women, young people, and those with higher incomes are more likely to keep dogs and cats, and the primary reason is to gain emotional support. Our study provides insights into why humans get so attached to dogs and cats and establishes a foundation for developing co-evolutionary models.

Introduction Livestock abortigenic agents, which are microorganisms that lead to premature foetal death and expulsion before completion of the gestation period, are common in Africa and Asia. Abortion events cause economic losses by lowering reproduction (and hence herd/flock sizes) and effects on milk production. Despite the importance of livestock production for food security and livelihoods of millions of the world’s poorest communities, very little is known about the scale, magnitude or causes of livestock abortion in Africa. The aim of this review was to determine the current status of the burden of livestock abortion and surveillance measures adopted for livestock abortigenic pathogens in Africa and Asia, and to explore feasible surveillance technologies. Methodology A systematic literature search was conducted using Preferred Reporting of Systematic Reviews and Meta-analyses (PRISMA) guidelines in four databases for studies published between 1 Jan 1990 and 31 July 2021 that reported epidemiological surveys of livestock abortigenic pathogens in cattle, goats and sheep in Africa and Asia including; Brucella spp., Neospora caninum, Toxoplasma gondii, Rift valley fever virus, Coxiella burnetii, Chlamydia, Leptospira and Bovine viral Diarrhoea Virus. A meta-analysis was used to estimate the species-specific prevalence of the abortigenic diseases and the region where they were detected. Results In the systematic literature search, 48 full papers were included which in total included 50 species-specific surveillance reports from Africa and 19 from Asia. Adjusted median seroprevalence calculations estimated Brucella at 6.85% (range 1.2-11.6) of 9071 sheep, 3.35% (range 0.90-5.40) of 17,007 goats, 8.95% (range 0.50-63.60) of 171,733 cattle, Neospora at 6.80% (range 6.80 -6.80) of 555 sheep, 10.80 (range 10.80-10.80) of 185 goats, 12.65% (range 3.40- 25.60) of 3775 cattle, Toxoplasma at 27.50% (range 1.40 – 75.90) of 2284 sheep, 32.0% (range 20.00- 64.80) of 1226 goats, 7.50% (range 7.50 - 7.50) of 174 cattle, Coxiella at 9.20 (range 9.20 – 9.20) of 184 sheep, 24.20% (range 24.20-24.20) of 91 goats, 13.80% (range 13.80-13.80) of 217 cattle, Rift valley fever virus at 7.70 (2.40-40.00) of 874 sheep, 20.95 (range 2.50-40.00) of 547 goats, 7.45% (range 3.60-11.30) of 309 cattle, Bovine viral diarrhea virus at 78.90 (range 78.90 – 78.90) of 398 cattle, Leptospira at 70.50 (range 70.50 – 70.50) of 373 cattle and Chlamydia at 6.60 (6.60-6.60) of 803 sheep. We found that most studies, 45 (89%) used serological surveys, 1 (2%) used molecular and 1 (2%) reported to have used Mobile-phone based surveillance approach. Three studies (6.25%) of the 48 included were embedded in the national surveillance programs of the respective countries they were conducted, majority 89% were stand-alone cross-sectional studies. Conclusion In conclusion, livestock abortigenic pathogens are still a burden in many African and Asian countries.

Hepatitis B surface antigen (HBsAg) is not only the biomarker of hepatitis B virus (HBV) infection and expression activity in hepatocytes, but also contributes to viral specific T cell exhaustion and HBV persistent infection. Therefore, anti-HBV therapies targeting HBsAg to achieve HBsAg loss are key approaches for HBV functional cure. In this study, we found that YZH-106, a rupestonic acid derivative, inhibited HBsAg secretion and viral replication. Further investigation demonstrated that YZH-106 promoted the lysosomal degradation of viral L- and M-HBs proteins. Mechanistic study by Biacore and docking analysis revealed that YZH-106 bound directly to PreS2 domain of L- and M-HBsAg, thereby blocking their entry to the endoplasmic reticulum (ER) and promoting their degradation in cytoplasm. Our work thereby provide basis for design of novel compound therapy to target HBsAg against HBV infection.

Nanotechnology has applications in a variety of scientific specialties, encompassing health, technological devices, and now cosmetics under the generic term of nanocosmetics. Due to the improved particle qualities, such as color, transparency, and solubility, acquired at the nanoscale, nanotechnology significantly affects the cosmetic industry. Skin penetration mechanism depends heavily on the nanoparticles' physicochemical properties, including stiffness, hydrophobicity, size, and charge. An expanding industry that requires more research and development has been created by nanoparticle production technologies. Liposomes, solid lipid nanoparticles, cubosomes, dendrimers, and other nanomaterials offer advanced skincare properties. Cosmetics made using nanotechnology have the advantages of product diversity, increased bioavailability of active compounds, and enhanced pleasing appearance of cosmetics with long-lasting benefits. The various cosmetic brands' utilization of various types of nanomaterials in their products is highlighted in this review.

Global stress is widespread in todays post-pandemic world of political and economic uncertainty. Vibroacoustic technology is a vibrotactile intervention with multiple uses, and its impact on stress lacks interpretation. This research assessed if the vibroacoustic technology of a Vibroacoustic Sound Massage (VSM) can reduce psychological, physiological and cognitive stress. The Perceived Stress Scale (PSS-10), and electrocardiogram (ECG) and electroencephalogram (EEG) biosignals were used to quantify results. Participants were divided into Low Stress and High Stress groups. ECG results show VSM increased parasympathetic activity for all participants, with the Low Stress group more effected. EEG results indicate increased concentration (TBR), reduced arousal and increased relaxation (BAR), and non-significant effects on participant well-being (FAA), though variability in this metric was homogenised after VSM. Together, these results validate VSM as an effective support tool for stress management and further research is required.

Plant growth promoting rhizobacteria (PGPR) are a diverse group of microorganisms including genera such as Pseudomonas, Bacillus, Serratia, Enterobacter and Klebsiella. These bacteria have the ability to colonize roots externally and internally, and to directly enhance plant growth employing various mechanisms like phytohormone production and nutrient mineralization. These microbes can also promote plant growth indirectly by secreting antimicrobial compounds (e.g., siderophores, hydrogen cyanide) to antagonize root pathogens or by inducing defensive responses in the plant. Interestingly, there are also cases where production of antibiotic compounds such as 2,4-Diacetylphloroglucinol have the direct effect of enhancing plant growth and yield, irrespective of their biocontrol effects. The objective of this paper is to review publications showcasing PGPRs that have the capacity to both control root pathogens and stimulate plant growth, and to discuss what mechanisms might be involved.

Antler is the fastest growing tissue. Because is based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus its extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound testing direct effects in cells of different tumours: glioblastoma (GBM), colorectal and breast cancer, and leukaemia. DVA reduced viability of tumour but not healthy cells. Mobility decreased at least at the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight 66.3% and 61.4% respectively, and also spleen weight. In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related with tumour fighting and down-regulated those related with inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system.

The gastrointestinal tract is colonized by trillions of different microorganisms, named the gut microbiota, which is key to degrade undigested food such as dietary fibers. The fermentation of these food components leads to the production of short-chain fatty acids (SCFA) acetate, propionate, and butyrate, which exploit several beneficial roles for the host’s health. Their production and absorption happen in different ways in the human intestine and depend on the type of dietary fiber reaching the gut and the microorganisms involved in the fermentation. The supplementation of SCFAs, mostly butyrate, in treating gastrointestinal, metabolic, cardiovascular, and gut-brain-related diseases has been reported in the medical literature. This review aims to give an overview of the production and absorption dynamics of acetate, propionate, and butyrate in the human gut, with a final focus on the role played by these SCFAs on gastrointestinal and metabolic health and the present therapeutic implications.

Technological advances in DBS hardware and software represent a significant growth area in functional neurosurgery. These advancements have the potential to significantly enhance treatment outcomes and expand the scope of neurological disorders that can be effectively addressed through DBS interventions. The introduction of directional DBS marks a new phase in neuromodulation, offering extended benefits for patients with Parkinson's disease, more efficient optimization of clinical outcomes, and targeted treatment of refractory symptoms through data-driven approaches. Implementing a multimodal programming strategy, incorporating novel current fractionation technology and image-guided tools for lead localization and brain sensing, further reduces reliance on traditional trial-and-error programming methods, paving the way for a more predictive application of this therapy. These advancements are expected to drive the development of sophisticated closed-loop stimulation systems capable of integrating continuous data streams for improved patient care.

Transcranial photobiomodulation (tPBM) has been suggested as a non-invasive neuromodulation tool. Repetitive administration of light-emitting diode (LED)-based tPBM for several weeks significantly improved human cognition. To understand the electrophysiological effects of LED-tPBM on the human brain, we investigated alterations by repeated tPBM in vigilance performance and brain networks using electroencephalography (EEG) in healthy participants. Active and sham LED-based tPBM were administered to the right forehead of young participants twice a week for four weeks. The participants performed a psychomotor vigilance task (PVT) during each tPBM/sham experiment. A 64-electrode EEG system recorded electrophysiological signals from each participant during the first and last visits in the 4-week study. Topographical maps of EEG power enhanced by tPBM were statistically compared for the repeated tPBM effect. A new data-processing framework combining the group singular value decompensation (gSVD) with eLORETA was implemented to identify EEG brain networks. The reaction time of PVT in the tPBM-treated group was significantly improved over four weeks compared to that in the sham group. We observed acute increases in EEG delta and alpha powers during 10-min LED-tPBM while the participants performed the PVT task. We also found that theta, beta, and gamma EEG powers significantly increased globally after four weeks of LED-tPBM. Combining gSVD with eLORETA enabled us to identify EEG brain networks and the corresponding network power changes by repeated 4-week tPBM. This study clearly demonstrated that 4-week prefrontal LED-tPBM can neuromodulate several key EEG networks, implying a possible causal effect between modulated brain networks and improved psychomotor vigilance outcomes.

As the additive manufacturing industry grows, it is compounding the global plastic waste problem. Distributed recycling and additive manufacturing (DRAM) offers an economic solution to this challenge, but it has been relegated to either small-volume 3D printers (limiting waste recycling throughput) or expensive industrial machines (limiting accessibility and lateral scaling). To overcome these challenges, this paper provides proof-of-concept for a novel open-source hybrid 3D printer that combines a low-cost hanging printer design with a compression screw-based end-effector that allows direct extrusion of recycled plastic waste in large expandable printing volumes. Mechanical testing of the resultant prints from 100% waste plastic, however, showed that combining challenges of non-uniform feedstocks and a heavy printhead for a hangprinter reduced the strength of the parts compared to fused filament fabrication. The preliminary results are technologically promising, however, and provide opportunities to improve on the open source design to help process the volumes of waste plastic needed for DRAM to address the negative environmental impacts of global plastic use.

Hydrogen is now recognized as the primary alternative to fossil fuels due to its renewable, safe, high energy density and environmentally friendly properties. Efficient hydrogen production through water splitting has laid the foundation for sustainable energy technologies. However, when hydrogen production is scaled up to industrial levels, operating at high current densities introduces unique challenges. It is necessary to design advanced electrocatalysts for hydrogen evolution reaction (HER) under high current densities. This review will briefly introduce chal-lenges posed by high current densities on electrocatalyst, including catalystic activity, mass dif-fusion and catalyst stability. In an attempt to address these issues, various electrocatalyst design strategies are summarized in detail. In the end, our insights into future challenges for efficient large-scale industrial hydrogen production from water splitting are presented. This review is expected to guide the rational design of efficient high current density water electrolysis electro-catalysts and promote the research progress of sustainable energy.

During the COVID-19 pandemic, the spread of the SARS-CoV-2 virus forced many individuals to confront their mortality and worry about losing loved ones also because social distancing policies often made it impossible to say goodbye. Those not directly experiencing loss were inundated with information about COVID-19-related deaths through various media, leading to vicarious grief. This study aims to explore the long-term effects of direct and vicarious mourning on people's mental health during the COVID-19 pandemic. A sample of 171 adults (65% female) aged 19 to 66 years (mean age = 25.8, SD = 8.57) voluntarily participated in an online survey assessing self-reported psychological measures of complicated grief, anxiety, stress, depression, dispositional neuroticism, and situational anxiety using the Fear of COVID-19 Scale. MANOVA tests revealed that individuals experiencing direct mourning had extremely severe scores for anxiety, stress, and fear of COVID-19, while those without personal losses had moderate scores. Participants reporting high media exposure had higher scores for depression and stress. In line with Terror Management Theory, the study supported that people during the COVID-19 pandemic engaged more in proximal defenses than distal ones, taking health-protective measures, experiencing increased anxiety levels toward SARS-CoV-2 infection, and feeling more distressed. Additionally, vicarious mourning was more strongly associated with depression due to emotional empathy with others. The discussion also addresses the strengths and limitations of the study.

Fibrodysplasia Ossificans Progressiva (FOP) is an enigmatic, ultra-rare genetic disorder characterized by progressive heterotopic ossification, wherein soft connective tissues undergo pathological transformation into bone structures. This incapacitating process severely limits patient mobility and poses formidable challenges for therapeutic intervention. Predominantly caused by missense mutations in the ACVR1 gene, the disorder has hitherto defied comprehensive mechanistic understanding and effective treatment paradigms. This write-up offers a comprehensive overview of the contemporary understanding of FOP's complex pathobiology, underscored by advances in molecular genetics and proteomic studies. We shed light on targeted therapy, spanning genetic therapeutics, enzymatic and transcriptional modulation, stem cell therapies, and innovative immunotherapies. We also focused on the intricate complexities surrounding clinical trial design for ultra-rare disorders like FOP, addressing fundamental statistical limitations, ethical conundrums, and methodological advancements essential for the success of interventional studies. We advocate for the adoption of a multi-disciplinary approach that converges bench-to-bedside research, clinical expertise, and ethical considerations to tackle the challenges of ultra-rare diseases like FOP and comparable ultra-rare diseases. Overall, this article serves a dual role: as a definitive scientific resource for ongoing and future FOP research and as a call to action for innovative solutions to address methodological and ethical challenges that impede progress in the broader field of medical research for ultra-rare conditions.

This paper presents the rationale for using ultra low intensity transcranial light photodynamic treatment (LIT-PDT) for treating glioblastoma. Glioblastoma is currently treated with maximal safe resection, temozolomide and ionizing irradiation. Mortality in 2024 remains at over 80% within several years from diagnosis. 5-aminolevulinic acid (5-ALA) is a heme precursor that is selectively taken up preferentially by malignant cells, including glioblastoma. Photon energy can be transduced to molecular oxygen by a 5-ALA metabolite, PpIX, transforming oxygen to the singlet state, a reactive oxygen species (ROS) that destroys or damages vital glioblastoma cell structures. In PDT, light energy ~ 100 to 200 J / cm2, at 630 nm is delivered intraoperatively after resection and preoperative oral 5-ALA. This generates ROS cytotoxicity in residual glioblastoma cells within the resection cavity wall. 630 nm light poorly penetrates skin, skull, and brain tissue. That currently restricts PDT to a single intraoperative session using high flux light. LIT-PDT addresses some current shortcomings of 5-ALA PDT treatment. Part 1 analyzes published data indicating that continuous ultra low light flux, 17 μW / cm2, over 24 hours for a total delivery of 1.5 J / cm2, is effective for 5-ALA PDT treatment. That opens the way for repetitive, extracranial light to deliver enough energy for low flux, long duration PDT to any deep brain structure using less than 12 W total distributed over the entire scalp area. In Part 2, by analysis of 5-ALA and PpIX physiology, it became apparent that four non oncology drugs - ciprofloxacin, deferiprone, telmisartan and ziprasidone, will increase energy capture by GB cells, thereby increasing PDT treatment cytotoxicity. A phased pilot study of LIT-PDT treatment is being planned.

This article presents a buck converter in which the inductor has been replaced by a transmission line. This approach would be practically conceivable if the power supply and load have a greater spatial distance. In the time domain, this new converter can be described by a system of coupled partial and ordinary differential equations. In the frequency domain, a transcendental transfer function is obtained. For comparison with an equivalently parameterized conventional converter, Padé approximants are derived. A linear controller is designed for the converter topology under consideration.

European Union (EU) regulations on in vitro diagnostics (IVD) and on serious cross-border threats to health provide for the establishment of European Reference Laboratories (EURLs) and their harmonisation and cooperation with National Reference Laboratories (NRLs). While the EURLs under the IVD Regulation will be operational by 1 October 2024, the EURLs under the Regulation on serious cross-border threats to health will be operational by January 2025. Although NRLs may have been operating for a long time on the basis of national legislation, they should now cooperate with each other and with EURLs in a network of centres of excellence for the authorisation and post-market surveillance of IVDs and for the epidemiological surveillance and control of communicable diseases. The term "reference laboratory" has long been used colloquially to refer to many kinds of laboratories, regardless of their tasks, competencies, responsibilities and designation. To clarify the roles and functioning of EURLs and NRLs, we evaluated the relevant current EU provisions and compared the findings with those of reference laboratories designated by other organisations, calibration (reference) laboratories and referral laboratories, which are simply referred to as "reference laboratories".

Objective: To evaluate the direct costs of treating patients with neuromyelitis optica spectrum disorders (NMOSD) in outpatient care, from a hospital and Unified Health System (SUS) perspective. Methods: Observational study with data collection by microfunding, carried out with patients diagnosed with neuromyelitis optics, treated at a university hospital, in the city of Rio de Janeiro. Mann-Whitney tests were performed to measure cost differences between patient groups by disease severity and analysis perspective. Results: Nine individuals with a median age of 48 years (IQR 30 - 59 years) were included. The median total costs for patients with greater severity from the perspective of the SUS and the hospital were R$ 21,638.22 (IIQ: R$ 15,614.63; R$ 25,985.32) and R$ 32,094.11 (IIQ: R$ 25,610 .60; R$ 38,617.25) respectively. For patients with moderate severity the median was R$ 7,339.85 (IIQ: R$ 6,235.45; R$ 11,912.05) from the SUS perspective and R$ 11,505.80 (IIQ: R$ 7,339.85; R$ 22,424.76) from the perspective of the hospital, where the use of medications had a major impact. Conclusion: The main cost drivers were medicines, especially those used off-label, and procedures.

A chronically stable electrode material with low impedance for recording neural activity and high charge-injection capacity for functional electro-stimulation is desirable for the fabrication of implantable microelectrode arrays that aims to restore impaired or lost neurological functions in humans. For this purpose, we have investigated the electrochemical properties of sputtered ruthenium oxide (RuOx) electrode coatings, deposited on planar microelectrode arrays, using an inorganic model of interstitial fluid (model-ISF) at 37o C as the electrolyte. Through a combination of cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) modelling study we have established the contribution of faradaic reaction as the major charge-injection contributor within the safe neural stimulation potential window of 0.6 V vs Ag|AgCl. We have also established the reversibility of the charge-injection process for sputtered RuOx film by applying constant charge-per-phase current stimulations at different pulse widths and by comparing the magnitudes of leading and trailing access voltages during voltage transient measurements. Finally, the impedance of the sputtered RuOx film was found to be reasonably comparable in both its oxidized and reduced states, although electronic contribution from capacitive double-layer was found to be slightly higher for the completely oxidized film around 0.6 V than its reduced counterpart around -0.6V.

Land transportation is contributing to global greenhouse gas (GHG) emissions significantly. Switching from gasoline-powered vehicles to electric vehicles (EVs) is the most practical way to decarbonize land transportation. Some regions of the world have seen significant advancements in the adoption of electric vehicles, largely due to government policies through subsidies and other rules and laws that globally made the cost of acquisition and ownership more advantageous for EV owners compared to their internal combustion engine (ICE) counterparts. The success of EV adoption in Norway, China, the United States of America (USA), the European Union (EU), and India has been linked to the favorable government policies. At present, China is the largest EV market in the world, enjoying a better advantage than any other market. It also has the highest manufacturing capacity and the largest number of EVs in operation. Norway has the highest EV penetration rate, with over 90% of newly registered cars, and one of the lowest costs of ownership globally. In this review, we present the current state of EV technology and performance, together with consumer perspectives and barriers, EV regulations in the regions with the highest penetration rates, and the decarbonization of land transportation. China is competing with the USA for leadership in manufacturing and technology, especially in the areas of artificial intelligence (AI) and batteries. In order to achieve the goal of decarbonizing road transportation, we proposed that a number of factors, including government energy policies and regulatory standard development, necessary infrastructure investments and developments, AI incorporation in EVs, innovation in EV and battery technologies, and consumer perspectives, play a crucial role.