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Abstract Background The present study was aimed at investigating the writing parameters of writer's cramp patients and control subjects during handwriting of a test sentence in the absence of visual control. Methods Eight right-handed patients with writer's cramp and eight healthy volunteers as age-matched control subjects participated in the study. The experimental task consisted in writing a test sentence repeatedly for fifty times on a pressure-sensitive digital board. The subject did not have visual control on his handwriting. The writing performance was stored on a PC and analyzed off-line. Results During handwriting all patients developed a typical dystonic limb posture and reported an increase in muscular tension along the experimental session. The patients were significantly slower than the controls, with lower mean vertical pressure of the pen tip on the paper and they could not reach the endmost letter of the sentence in the given time window. No other handwriting parameter differences were found between the two groups. Conclusion Our findings indicate that during writing in the absence of visual feedback writer's cramp patients are slower and could not reach the endmost letter of the test sentence, but their level of automatization is not impaired and writer's cramp handwriting parameters are similar to those of the controls except for even lower vertical pressure of the pen tip on the paper, which is probably due to a changed strategy in such experimental conditions.

The identification of cancer stem cells in various malignancies led to the hypothesis that these cells have the exclusive ability of self-renewal, contribute to the plasticity of the tumours and may be the cause for ineffective cancer therapies. Several markers of melanoma stem cells have been described in recent studies including CD133, CD166, Nestin and BMI-1. Further studies are necessary to identify, better define and understand the origin and function of cancer stem cells. If confirmed that cancer stem cells play an important role in malignancy, therapeutic strategies may need to be redirected towards these cells to circumvent the failure of conventional therapies. [ABSTRACT FROM AUTHOR]

A correction to the article "Cancer stem cells in melanoma" that was published in the previous issue is presented.

Premise: Plants generate a wide array of signals such as olfactory cues to attract and manipulate the response of pollinators. The present study addresses the temporal patterns of scent emission as an additional dimension to the scent composition. The expectation is that divergent floral function is reflected in divergent qualitative and temporal emission patterns., Methods: We used GC-ion mobility spectrometry with an integrated pre-concentration for automated acquisition of the temporal trends in floral volatile emissions for N. viridiflorus, N. papyraceus, and N. cantabricus subsp. foliosus., Results: We found a considerable increase in scent emissions and changes in scent composition for N. viridiflorus at night. This increase was particularly pronounced for aromatic substances such as benzyl acetate and p-cresol. We found no diurnal patterns in N. papyraceus, despite a similar qualitative composition of floral volatiles. Narcissus cantabricus subsp. foliosus showed no diurnal patterns either and differed considerably in floral scent composition., Conclusions: Scent composition, circadian emission patterns, and floral morphology indicate divergent, but partially overlapping pollinator communities. However, the limited pollinator data from the field only permits a tentative correlation between emission patterns and flower visitors. Narcissus papyraceus and N. cantabricus show no clear diurnal patterns and thus no adjustment to the activity patterns of their diurnal pollinators. In N. viridiflorus, timing of scent emission indicates an adaptation to nocturnal flower visitors, contradicting Macroglossum as the only reported pollinator. We propose that the legitimate pollinators of N. viridiflorus are nocturnal and are still unidentified., (© 2024 The Author(s). American Journal of Botany published by Wiley Periodicals LLC on behalf of Botanical Society of America.)

Objective: Self-management interventions may enhance health-related quality of life (HRQoL) in epilepsy. However, several barriers often impair their implementation in the real world. Digital interventions may help to overcome some of these barriers. Considering this, the Helpilepsy Plus Prototype was developed as a prototype smartphone-delivered self-care treatment program for adults with epilepsy., Methods: The 12-week Helpilepsy Plus Prototype was evaluated through a randomized controlled feasibility trial with a waiting-list control (WLC) group. Outcome measurement at baseline and at 12 weeks assessed adherence to the prototype intervention and changes in epilepsy-related outcomes. The primary endpoint was patient autonomy measured with EASE, and secondary endpoints included HRQoL measured with QOLIE-31, health literacy measured with HLQ, anxiety, and depression symptoms measured with HADS. Semi-structured interviews were conducted with a heterogeneous sample of participants to assess user-friendliness and usefulness. The prototype program was delivered through the Neuroventis Platform (Neuroventis, BV, Overijse, Belgium), a certified medical device (under EU/MDD Class I, and EU/MDR grace period)., Results: Ninety-two patients were included (46 in the intervention group, 46 in WLC). Most participants (63%, 58/92 women, median age 30 years) had pharmacoresistant epilepsy (61%, 56/92). Only 22% of participants (10/46) in the intervention group completed at least half of all intervention sessions. No significant differences between the intervention group and WLC were observed. Although there was a larger proportion of patients in the intervention group with meaningful improvements in HRQoL compared to WLC (19/46 versus 11/46), the difference was not significant (p = 0.119). Qualitative feedback showed that participants would appreciate more personalization, such as adaptation of the content to their current epilepsy knowledge level, a more interactive interface, shorter text sections, and interaction through reminders and notifications., Significance: Digital interventions should allow sufficient scope for personalization and interaction to increase patient engagement and enable benefits from self-care apps. Feedback loops allow the participatory development of tailored interventions., Plain Language Summary: In this study, we investigated the effectiveness of an app-based self-help intervention. Study participants were either randomly assigned to a group that had access to the app or a group that received access to the app after the end of the study. Although a larger proportion of participants in the intervention group showed a relevant improvement in quality of life, the difference between the two groups was not statistically significant. Less than one-fifth of participants in the intervention group attended at least half of all intervention sessions; patient feedback showed that patients required more personalization and interactive options., (© 2024 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Plants emit a range of volatile organic compounds (VOCs) as a way of interacting with their biotic and abiotic surroundings. These VOCs can have various ecological functions, such as attracting pollinators, repelling herbivores, or may be emitted in response to abiotic stress. For the present dataset, we used gas chromatography coupled ion mobility spectrometry (GC-IMS) to analyse the VOCs emitted by different plant species under controlled conditions. GC-IMS is a rapid and sensitive technique for gas phase analysis, that separates VOCs based on their retention time and drift time, resulting in characteristic heatmaps where the xy-position of a signal corresponds to compound identity, while signal intensity reflects its abundance. In this dataset, rapid analysis by GC-IMS was used to record emission pattern of 140 plant species from different taxonomic groups. This includes both floral volatiles and emission from leaves after induced damage. The data was pre-evaluated and listed in one table, containing information on the plant material used, as well as information on the respective emission patterns (including already identified compounds). Thus, this dataset provides a broad overview over plant VOC emissions. These can be used to either check the distribution of knowns substances, or the specific emissions of plants for functional, ecological or physiological studies or as the starting point for chemotaxonomic studies. The extraordinary ease with which these data can be generated - with the suitable set-up - lends itself to larger scale systematic or ecological studies across plant (or animal) groups and even ecosystems., (© 2024 The Author(s).)

Premise: Daffodils ( Narcissus , Amaryllidaceae) are iconic ornamentals with a complex floral biology and many fragrant species; however, little is known about floral plant volatile organic compounds (pVOCs) across the genus and additional sampling is desirable. The present study investigates whether the floral scent of 20 species of Narcissus can be characterized using gas chromatography - coupled ion mobility spectrometry (GC-IMS), with the aim of building a comparative pVOC data set for ecological and evolutionary studies., Methods: We used a commercial GC-IMS equipped with an integrated in-line enrichment system for a fast, sensitive, and automated pVOC analysis. This facilitates qualitative and (semi)-quantitative measurements without sample preparation., Results: The GC-IMS provided detailed data on floral pVOCs in Narcissus with very short sampling times and without floral enclosure. A wide range of compounds was recorded and partially identified. The retrieved pVOC patterns showed a good agreement with published data, and five "chemotypes" were characterized as characteristic combinations of floral volatiles., Discussion: The GC-IMS setup can be applied to rapidly generate large amounts of pVOC data with high sensitivity and selectivity. The preliminary data on Narcissus obtained here indicate both considerable pVOC variability and a good correspondence of the pVOC patterns with infrageneric classification, supporting the hypothesis that floral scent could represent a considerable phylogenetic signal., (© 2023 The Authors. Applications in Plant Sciences published by Wiley Periodicals LLC on behalf of Botanical Society of America.)

Reactions that require strictly dry conditions are challenging to translate to a DNA-encoded library format. Controlled pore glass solid support-connected DNA oligonucleotide-aldehyde conjugates could be condensed with SnAP reagents and cyclized to various sp 3 -rich heterocycles. The Boc-group of products provided a handle for product purification, and its facile removal under acidic conditions was tolerated by a chemically stabilized barcode. The reaction provides reagent-based scaffold diversity with functionalities for further library synthesis.

Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug (AED) approved as monotherapy for partial-onset seizures in adults and as adjunctive therapy in patients aged above 6 years in the European Union (EU). The prospective observational Zebinix Effects in DEpendency of BAseline Conditions (ZEDEBAC) study aimed at investigating the effectiveness of ESL in clinical practice, with ESL being administered as monotherapy (mono group), as only add-on to a current monotherapy (1+ group), or as add-on to ≥2 baseline AEDs (≥2+ group). In total, 237 patients were included, 35 in the mono group, 114 in the 1+, and 88 in the ≥2+ group. Six-month retention rates were 93.9%, 78.0%, and 75.3% in the mono, 1+, and ≥2+ group. There were 90.5%, 77.6%, and 48.3% of patients in the mono, 1+, and ≥2+ groups who were responders (patients with a ≥50% reduction in seizure frequency at follow-up vs. baseline). Seizure freedom rates were 81.5%, 47.9%, and 23.4%, respectively. Adverse drug reactions (ADRs) occurred in 11.4% of patients of the mono, 19.3% of the 1+, and 28.4% of patients of the ≥2+ group. Hyponatremia was reported as ADR in 3.4% of all patients. Although baseline variables differed considerably, with most elderly patients with tumor-related and vascular etiologies in the mono group and most patients with refractory epilepsies with pronounced use of concomitant sodium channel blockers (SCBs) in the ≥2+ group, retention as a measure of real-life effectiveness turned out not to be substantially different and favorable in all groups., (Copyright © 2019 Elsevier Inc. All rights reserved.)

DNA-encoded compound libraries are a widely used technology for target-based small molecule screening. Generally, these libraries are synthesized by solution phase combinatorial chemistry requiring aqueous solvent mixtures and reactions that are orthogonal to DNA reactivity. Initiating library synthesis with readily available controlled pore glass-coupled DNA barcodes benefits from enhanced DNA stability due to nucleobase protection and choice of dry organic solvents for encoded compound synthesis. We screened the compatibility of solid-phase coupled DNA sequences with 53 metal salts and organic reagents. This screening experiment suggests design of encoded library synthesis. Here, we show the reaction optimization and scope of three sp 3 -bond containing heterocyclic scaffolds synthesized on controlled pore glass-connected DNA sequences. A ZnCl 2 -promoted aza-Diels-Alder reaction with Danishefsky's diene furnished diverse substituted DNA-tagged pyridones, and a phosphoric acid organocatalyst allowed for synthesis of tetrahydroquinolines by the Povarov reaction and pyrimidinones by the Biginelli reaction, respectively. These three reactions caused low levels of DNA depurination and cover broad and only partially overlapping chemical space though using one set of DNA-coupled starting materials., (This journal is © The Royal Society of Chemistry 2019.)

DNA-encoded libraries of chemically synthesized compounds are an important small molecule screening technology. The synthesis of encoded compounds in solution is currently restricted to a few DNA-compatible and water-tolerant reactions. Encoded compound synthesis of short DNA-barcodes covalently connected to solid supports benefits from a broad range of choices of organic solvents. Here, we show that this encoded chemistry approach allows for the synthesis of DNA-coupled isoquinolones by an Yb(iii)-mediated Castagnoli-Cushman reaction under anhydrous reaction conditions and for the synthesis of highly substituted pyrrolidines by Ag(i)-mediated 1,3-dipolar azomethine ylide cycloaddition. An encoding scheme for these DNA-barcoded compounds based on a DNA hairpin is demonstrated.

Background: In patients taking antiepileptic drugs (AEDs) for epilepsy, adverse effects (AEs) often lead to unfavorable quality of life, impaired adherence, and, eventually, discontinuation of pharmacological treatment. In a true-to-life sample of subjects from our academic epilepsy outpatient clinic, we aimed to identify predictors for overall high AE burden and for specific AEs focusing on patients on monotherapy., Methods: All patients ≥16years of age with epilepsy for ≥12months were routinely asked to complete the Liverpool Adverse Event Profile (LAEP) just before their appointment. Demographic, epilepsy, and treatment variables were derived from our comprehensive outpatient database., Results: Out of 841 patients, 438 (61% female, mean age: 44.7±17.1years) on monotherapy were included in this study. Levetiracetam (n=151), lamotrigine (n=167), valproic acid (n=73), or controlled-release carbamazepine (n=47) were the most commonly used antiepileptic drugs (AEDs). Independent predictors for general high AE burden (LAEP score≥45) were duration of epilepsy, lack of 12-month seizure freedom, and partial epilepsy, but none of the four individual AEDs. The most frequent LAEP-defined specific AEs were sleepiness, difficulty concentrating, tiredness, and memory problems. The three most frequent independent predictors for each of the 19 AEs were lack of 12-month seizure freedom (13/19 AEs), individual AED (7/19 AEs), and partial epilepsy (6/19 AEs). Levetiracetam was independently associated with anger/aggression, nervousness/agitation, upset stomach, depression, and sleep disturbance; lamotrigine with nervousness/agitation, upset stomach, and difficulty concentrating; and valproic acid with upset stomach and shaky hands., Conclusion: Individual AEDs independently predicted some specific AEs, but not overall high AE burden. Our findings may help to characterize patients with epilepsy who are at high risk for specific AEs. Dose reduction or change to another AED may reduce LAEP score and potential nonadherence., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Motor recovery after stroke is attributed to neuronal plasticity, however not all post-stroke neuronal changes relate to regaining fine motor control. Corticomuscular coherence (CMC) is a measure allowing to trace neuronal reorganizations which are functionally relevant for motor recovery. Contrary to previous studies which were performed only in chronic stage, we measured CMC in patients with stroke at both acute and chronic stroke stages., Methods: For the detection of CMC we used multichannel EEG and EMG recordings along with an optimization algorithm for the detection of corticomuscular interactions., Results: In acute stroke, the CMC amplitude was larger on the unaffected side compared to the affected side and also larger compared to the unaffected side in the chronic period. Additionally, CMC peak frequencies on both sides decreased in the acute compared to the chronic period and to control subjects. In chronic stage, there were no inter-hemispheric or group differences in CMC amplitude or frequency., Conclusions: The changes in CMC parameters in acute stroke could result from a temporary decrease in inhibition, which normalizes in the course of recovery. As all patients showed very good motor recovery, the modulation of CMC amplitude and frequency over time might thus reflect the process of motor recovery., Significance: We demonstrate for the first time the dynamical changes of corticomuscular interaction both at acute and chronic stage of stroke., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Cortico-muscular coherence (CMC) reflects interactions between muscular and cortical activities as detected with EMG and EEG recordings, respectively. Most previous studies utilized EMG rectification for CMC calculation. Yet, recent modeling studies predicted that EMG rectification might have disadvantages for CMC evaluation. In addition, previously the effect of rectification on CMC was estimated with single-channel EEG which might be suboptimal for detection of CMC. In order to optimally detect CMC with un-rectified EMG and resolve the issue of EMG rectification for CMC estimation, we introduce a novel method, Regression CMC (R-CMC), which maximizes the coherence between EEG and EMG. The core idea is to use multiple regression where narrowly filtered EEG signals serve as predictors and EMG is the dependent variable. We investigated CMC during isometric contraction of the abductor pollicis brevis muscle. In order to facilitate the comparison with previous studies, we estimated the effect of rectification with frequently used Laplacian filtering and C3/C4 vs. linked earlobes. For all three types of analysis, we detected CMC in the beta frequency range above the contralateral sensorimotor areas. The R-CMC approach was validated with simulations and real data and was found capable of recovering CMC even in case of high levels of background noise. When using single channel data, there were no changes in the strength of CMC estimated with rectified or un-rectified EMG--in agreement with the previous findings. Critically, for both Laplacian and R-CMC analyses EMG rectification resulted in significantly smaller CMC values compared to un-rectified EMG. Thus, the present results provide empirical evidence for the predictions from the earlier modeling studies that rectification of EMG can reduce CMC., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Recent investigations revealed strong immunosuppressive mechanisms in tumors that may block anti-tumor T cells and be responsible for failures of immunotherapies. Current attempts to overcome this immunosuppression include blockade of co-inhibitory factors on T cells. Reports from the respective trials indicate that the strategy can improve efficacy of therapeutic vaccination, but at the cost of severe inflammatory and autoimmune reactions. We tried to circumvent tumor-associated immunosuppression by mimotope vaccination to broaden reactive anti-tumor T cell repertoires to include T cells that have not been rendered anergic by the tumor. Initial clinical observations suggest that this strategy bears considerable promise.

The Berlin Brain--Computer Interface (BBCI) project develops a noninvasive BCI system whose key features are: 1) the use of well-established motor competences as control paradigms; 2) high-dimensional features from multichannel EEG; and 3) advanced machine-learning techniques. Spatio-spectral changes of sensorimotor rhythms are used to discriminate imagined movements (left hand, right hand, and foot). A previous feedback study [M. Krauledat, K.-R. MUller, and G. Curio. (2007) The non-invasive Berlin brain--computer Interface: Fast acquisition of effective performance in untrained subjects. NeuroImage. [Online]. 37(2), pp. 539--550. Available: http://dx.doi.org/10.1016/j.neuroimage.2007.01.051] with ten subjects provided preliminary evidence that the BBCI system can be operated at high accuracy for subjects with less than five prior BCI exposures. Here, we demonstrate in a group of 14 fully BCI-naIve subjects that 8 out of 14 BCI novices can perform at >84% accuracy in their very first BCI session, and a further four subjects at >70%. Thus, 12 out of 14 BCI-novices had significant above-chance level performances without any subject training even in the first session, as based on an optimized EEG analysis by advanced machine-learning algorithms.

Background: The present study was aimed at investigating the writing parameters of writer's cramp patients and control subjects during handwriting of a test sentence in the absence of visual control., Methods: Eight right-handed patients with writer's cramp and eight healthy volunteers as age-matched control subjects participated in the study. The experimental task consisted in writing a test sentence repeatedly for fifty times on a pressure-sensitive digital board. The subject did not have visual control on his handwriting. The writing performance was stored on a PC and analyzed off-line., Results: During handwriting all patients developed a typical dystonic limb posture and reported an increase in muscular tension along the experimental session. The patients were significantly slower than the controls, with lower mean vertical pressure of the pen tip on the paper and they could not reach the endmost letter of the sentence in the given time window. No other handwriting parameter differences were found between the two groups., Conclusion: Our findings indicate that during writing in the absence of visual feedback writer's cramp patients are slower and could not reach the endmost letter of the test sentence, but their level of automatization is not impaired and writer's cramp handwriting parameters are similar to those of the controls except for even lower vertical pressure of the pen tip on the paper, which is probably due to a changed strategy in such experimental conditions.

We investigated cortical activation as reflected in task-related spectral power (TRPow) changes in 8 writer's cramp patients during writing on a digital board and during isometric contraction and compared them to those of 8 age-matched healthy subjects. Scalp EEG was recorded over the contralateral primary sensorimotor area (SM1(c)), and from the ipsilateral sensorimotor area (SM1(i)). The electromyogram (EMG) was recorded from the Extensor Digitorum Communis (Extensor), Flexor Digitorum Superficialis (Flexor), and First Dorsal Interosseous (FDI) muscles. We analyzed (1) handwriting performance, (2) changes in the TRPow confined to alpha and beta band, and (3) the EMG spectral power during both tasks, writing and isometric contraction. During writing, all patients developed writer's cramp. The handwriting in writer's cramp patients was associated with significantly less reduction of the beta-range TRPow and lower frequency of the TRPow reduction compared to controls. No significant differences between patients and controls for the alpha band TRPow reduction during handwriting were observed. During writing, the patients showed higher EMG spectral power than the controls but this difference was at the border of significance. The present results indicate disorder in the motor execution system, in writer's cramp patients, associated with impaired functional beta-network state of the contra- and ipsilateral sensorimotor cortices, most probably due to inadequate modulation of the intracortical inhibition associated with writing.

To enhance human interaction with machines, research interest is growing to develop a 'brain-computer interface', which allows communication of a human with a machine only by use of brain signals. So far, the applicability of such an interface is strongly limited by low bit-transfer rates, slow response times and long training sessions for the subject. The Berlin Brain-Computer Interface (BBCI) project is guided by the idea to train a computer by advanced machine learning techniques both to improve classification performance and to reduce the need of subject training. In this paper we present two directions in which brain-computer interfacing can be enhanced by exploiting the lateralized readiness potential: (1) for establishing a rapid response BCI system that can predict the laterality of upcoming finger movements before EMG onset even in time critical contexts, and (2) to improve information transfer rates in the common BCI approach relying on imagined limb movements.