dataesr/scientific-paragraphs-categorization huggingface dataset:
In addition, open and uncontrolled reports covering a total of 63 patients were published, which reported beneficial outcomes with moderate to marked tic improvement in the vast majority of patients (59/63 patients). Since this review, five subsequent RCTs have been published, resulting in a total of 62 patients in all RCTs. Thus, until today there is still only a total of eight RCTs available including a maximum of 17 patients  [25] [26] [27] [28] [29] [30] [31] [32]. A summary of these studies is presented in Table  1. In addition, data from the International Deep Brain Stimulation Database and Registry including 185 patients (published in 2018  [33] ), one retrospective analysis on long-term follow-up in 110 patients (published in 2019  [34] ), and two meta-analyses (published in 2016 and 2018) including 58  [35]  and 156  [36]  patients were published.
The International Deep Brain Stimulation Database and Registry In 2018, data from a large international cohort were published based on the International Deep Brain Stimulation Database and Registry  [33]. At the time, this registry included 185 patients with otherwise treatment-refractory TS, who underwent DBS implantation between 2012 and December 2016 at 31 institutions in 10 different countries (exact details about methodology of the data collection and analysis can be consulted in the paper by Martinez-Ramirez et al. [33] ). The authors mainly focused on the efficacy of DBS in reducing tics at 6 and 12 months after DBS implantation as measured using the YGTSS-TTS) and the number and profile of adverse events (AEs) related to both surgery (such as infections and hemorrhage) and stimulation (such as paresthesias, bradykinesia, depression, and dystonia).
Target selection To date it is not clear which target should be selected in TS. The most often used targets are different parts of the thalamus (CM-Pf and CM/Voi) and the postero-ventrolateral and the anteromedial part of the GPi. However, several other targets have been suggested for the management of tics (and comorbidities) in TS including the NA, the ALIC, the globus pallidus externus (GPe), the subthalamic nucleus (STN) and the H Fields of Forel. According to both the International Deep Brain Stimulation Database and Registry and the two meta-analyses  [35, 36] , no significant differences between targets could be detected. However, both analyses reported that stimulation at the anteromedial GPi resulted in slightly, but nonsignificantly higher improvement rates compared to thalamic (centromedian region) DBS-followed by the postero-ventrolateral GPi.
Adverse events When evaluating the value of DBS in TS, type and frequency of AEs has to be considered too. According to the International Deep Brain Stimulation Database and Registry  [33] , more than one third of patients (35. 4%) experienced AEs. The most frequently reported AEs were stimulation-related (30. 8%) and included dysarthria and paresthesias. Dystonia and dyskinesias were more frequently reported after GPi DBS, while paresthesias and weight gain were more frequently reported after thalamic DBS. The only surgery-related AEs (in 3. 8%) were hemorrhage found in 1. 3% of cases and infections, which occurred with a rate of 2. 5%. Only 1. 3% of AEs were device-related. Overall, in TS the average rate of AEs after DBS seems to be similar compared to other patient populations such as dystonia and Parkinson's disease  [39, 126, 127].
In contrast to the data from the International Deep Brain Stimulation Database and Registry  [33] , but in line with other studies  [24, 25] , Servello et al. [72]  reported a higher risk of infections in patients with TS (18%, p < 0. 001) compared to other populations. In a recently published metaanalysis in different populations  [127] , a mean prevalence rate of surgical site infections of 5. 0% was reported. Infection rates above average were found in epilepsy (9. 5%), dystonia (6. 5%), and TS (5. 9%), while rates were lower in OCD (4. 5%), Parkinson's disease (3. 3%), essential tremor (2. 9%), and multiple sclerosis (2. 4%). It has been speculated that increased infection rate in TS might be related to complications caused by SIB or alternatively to an underlying immunological dysfunction related to the pathology of TS  [36].
However, in a recent study based on the cohort of the Tourette Association of America's International Tourette Syndrome Registry and Database  [128] , the incidence of lead removal was only 5. 6% and hence lower than previously reported rates in TS  [72]. Infections accounted for nearly half of DBS explantations in this cohort. Partly contradictory data might be explained by lack of harmonized methodology to assess AEs such as a unified questionnaire. Further details of the AE profile reported in RCTs and meta-analyses are given in Table  4.
Recommendations from recently published guidelines Since the publication of the first ESSTS DBS guidelines in 2011, further guidelines/recommendations specifically for DBS in patients with TS have been published: (i) in 2015 by the Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group  [129] , (ii) in 2019 by an international team of the American Academy of Neurology (AAN)  [5] , and (iii) in 2021 by an international group of experts  [130]. In addition, in 2014 members of different psychiatric and neurosurgical societies published more general consensus guidelines on DBS in psychiatric disorders  [131]. Conclusions from the systematic review of the AAN  [5]  were that (i) the optimal brain target for DBS in TS is still unknown, (ii) DBS of the anteromedial GPi seems to     [132]  recommended an age limit of 25 years (with rare potential exceptions).
However, AAN recommendations  [5] -as well as the consensus guidelines published in 2014  [131] -deserve some comment regarding the target selection. In both guidelines, an RCT published by Ackermans et al. [31]  describing the results of thalamic DBS in TS was not considered, presumably because of the small sample size of only six patients. The International Deep Brain Stimulation Database and Registry Study Group  [129]  gave the following recommendations: (i) patients qualified for the procedure should have a diagnosis of TS with severe motor and vocal tics, which did not respond to behavioral interventions per current expert standards and pharmacological treatments from three pharmacological classes (including alpha-adrenergic agonist, two dopamine antagonists (typical and atypical), and a drug from at least one additional class (e.
Updated recommendations of the ESSTS DBS guidelines group Currently no definite conclusions can be drawn on efficacy and safety of DBS in TS and many issues are still a matter of debate (Table  5 ). Therefore, surgical treatment should still be considered as an experimental therapeutic option for carefully selected patients with otherwise treatment-refractory tics. Noteworthy, RCTs consistently reported fewer positive effects on both tics and psychiatric comorbidities compared to data obtained from uncontrolled studies. This fact should also be taken into consideration when interpreting the results from the available data, meta-analyses, and from the International Deep Brain Stimulation Database and Registry, since the majority of these results are based on open and uncontrolled studies. Furthermore, there are specific DBSrelated methodological difficulties that may hamper RCTs (e.
(7) DBS should be performed in specialized centers by a dedicated multidisciplinary team including a psychi-1 3 atrist, psychologist and/or neurologist trained in the treatment of patients with TS. This multidisciplinary approach is not only required preoperatively (e. g. for correct diagnosing and assessment of inclusion criteria and judgement on "treatment-refractoriness"), but also during follow-up treatment with regular consultations of both surgical as well as psychiatric or neurological experts. (8) If possible, DBS should be performed following a specified protocol and within the context of a controlled trial, a cohort study, or registry database, but at least should include systematic pre-and post-DBS assessment of tics, premonitory urges, psychiatric comorbidities (including at least ADHD, OCD, depression, and anxiety), and quality of life.
No data are included from the International Tourette DBS Registry and Database, since no results on comorbidities were given Authors Study type N* Comorbidities assessed Results of the double blind phase Results of the open label phase Coulombe et al. [35]** M 58 Depression, anxiety, OCD Range of change of -75 to + 100% in OCD (Y-BOCS) Range of change of -2. 6 to + 58% in anxiety (STAI) Range of change of -80 to + 100% in depression (HAM-D) Range of change of -75 to + 100% in OCD (Y-BOCS) Range of change of -2. 6 to + 58% in anxiety (STAI) Range of change of -80 to + 100% in depression (HAM-D) Table 3.
published results of the largest retrospective analysis so far based on the International Deep Brain Stimulation Database and Registry involving 13 sites from North America (39 patients), Europe (63 patients) and Asia (21 patients). They assessed the effects of DBS in the long-term follow-up (up to 96 months) of 110 patients with TS, who were implanted in the CM-Pf and the CM/ Voi of the thalamus (n = 51), the GPi (n = 47), the NA/ALIC.
Conflict of interest JM has received speaker's honoraria from Abbott, Medtronic, Boston Scientific and BrainLab. CG received research grants from the VolkswagenStiftung (Freigeist Fellowship) and the German Parkinson Society and was also supported by the Deutsche Forschungsgemeinschaft (GA2031/1-1 and GA2031/1-2) and Actelion Pharmaceuticals. He also received financial support/ honoraria to speak at meetings by Actelion pharmaceuticals and as ad hoc advisory board for Lundbeck. CD has been awarded travel grants from Medtronic, Boston Scientific and Merz Pharma. AFGL received a research grant from the Michael J Fox Foundation and royalties from Springer media. TF received honoraria for talks sponsored by Boston scientific, Bial and Profile Pharma. He also was funded with grants from NIHR, Innovate UK, Cure Parkinson's trust, Michael J Fox foundation, John Black Charitable Foundation, Van Andel Insti-tute and Defeat MSA.
published results of the largest retrospective analysis so far based on the International Deep Brain Stimulation Database and Registry involving 13 sites from North America (39 patients), Europe (63 patients) and Asia (21 patients). They assessed the effects of DBS in the long-term follow-up (up to 96 months) of 110 patients with TS, who were implanted in the CM-Pf and the CM/ Voi of the thalamus (n = 51), the GPi (n = 47), the NA/ALIC [96] 4)or combinations of these targets (n = 8). Similarly to Baldermann et al. 's meta-analysis[36], the authors report that both tics and OCS significantly improved over time (p < 0. 01). The median time to reach a 40% improvement of tics was 13 months. However, no significant differences were found between different brain targets (p > 0. 05). Just recently, Kimura et al.
Statistical analyses Demographic and clinical data were compared between the two groups by using χ2-test for categorical variables and independent t-tests for continuous variables. Internal consistency was assessed by Cronbach's alpha coefficient. Convergent validity was calculated using the Pearson correlation coefficient between the SNS total score and the BPRS negative score, and between the SNS subscores and the corresponding subscores of SANS. Sensitivity and specificity were calculated using receiver-operator curve (ROC), with all the patients coded as 'cases' and all the controls as 'non-cases'.
A systematic electronic database search (PubMed and PsycINFO), following PRISMA guidelines, was conducted on autistic women's needs for care relating to psychiatric rehabilitation in romantic relationships and reproductive health. Out of 27 articles, 22 reported on romantic relationships and 16 used a quantitative design. Most studies were cross-sectional (n = 21) and conducted in North America or Europe. Eight studies reported on interventions addressing romantic relationships; no published study reported on interventions on reproductive health or parenting. Most interventions did not include gender-sensitive content (i. e. , gender variance and gender-related social norms, roles, and expectations). Autistic women and autistic gender-diverse individuals may face unique challenges in the domains of romantic relationships and reproductive health (high levels of stigma, high risk of sexual abuse, increased psychiatric symptoms, and more.
Sample Our sample contains 733 CEOs of US public companies from all industries during the period from 2006-2011. We used the S&P Capital IQ database to gather all the data used in this study. Capital IQ is a financial information platform that focuses on financial data and analysis for companies and industries, in addition to profiles of executives and details about M&A transactions. Specifically, Capital IQ provides information about the stock option packages of some of the CEOs of US public firms. We use this information to construct our measure of overconfidence, so the availability of detailed information about stock-option packages' value and vesting periods is the main screening criterion for the selection of the initial sample. For the period between 2006 and 2011, such detailed stock-option data are available for 733 individual CEOs for which we have 3 years of observations on average.
Statistical Analysis. Normality of data was tested using the Kolmogorov-Smirnov test. Intragroup and intergroup comparisons at different timepoints for RAVLT and Stroop variables were performed using two-way analysis of variance (ANOVA) followed by Dunnett's post hoc test. Greenhouse-Geisser corrections were applied for data that violated sphericity assumptions. e level of significance was set at 5% (p < 0. 05), and all analyses were run using GraphPad Prism software (GraphPad Software, Inc. , San Diego, CA, USA).
Acknowledgments is work was supported by  Innovative Medicines Initiative-Joint Undertaking  ( IMI-JU # 115621 ), by the  Nonprofit Research Foundation "Centro Studi Achille e Linda Lorenzon " and by a scholarship to H. J. C. -J. from  Coordenação de Aperfeiçoamento de Pessoal de Nível Superior  ( CAPES; Finance Code 001 ).
Roughly 10% of the human population is left-handed, and this rate is increased in some brain-related disorders. The neuroanatomical correlates of hand preference have remained equivocal. We re-sampled structural brain image data from 28,802 right-handers and 3,062 left-handers (UK Biobank population dataset) to a symmetrical surface template, and mapped asymmetries for each of 8,681 vertices across the cerebral cortex in each individual. Left-handers and right-handers showed average differences of surface area asymmetry within fusiform, anterior insular, anterior-middle-cingulate and precentral cortex. Meta-analyzed functional imaging data implicated these regions in executive functions and language. Polygenic disposition to left-handedness was associated with two of these regional asymmetries, and 18 loci previously linked with left-handedness by genome-wide screening showed associations with one or more of these asymmetries.
Vertex-wise correspondence between the left and right hemispheres was achieved through re-sampling each individual's cortical surface model to a symmetrical template created by inter-hemispheric co-registration  (34, 35). This surface-based registration approach aligns cortical folding patterns across individuals and both hemispheres. Using these data, we first aimed to identify specific clusters of vertices where cortical surface area or thickness asymmetries differed significantly at the group level between right and left-handers, for a uniquely well-powered and precision mapping analysis of the cortical correlates of hand preference. We then used meta-analyzed functional MRI (fMRI) data to annotate the cognitive and behavioural functions of the implicated cortical regions, based on independent studies.
Handedness is a weakly but significantly heritable trait, with estimates of the heritability due to common genetic polymorphisms ranging from 1. 2% to 5. 9% across different large-scale studies and cohorts  (36, 37). Recent large-scale genome-wide association studies have made progress on the identification of genetic influences on handedness  (26, 36, 37) , and separately also on brain structural asymmetry  (11). However, no study has previously investigated shared genetic influences on handedness and its specific cortical structural correlates. Using genome-wide genotype data for single nucleotide polymorphisms (SNPs) in the UK Biobank individuals, we tested the heritabilities of the cortical asymmetry measures at each regional cluster associated with hand preference, and also the genetic correlations between these regional cortical asymmetries.
Functional annotation of cortical regional asymmetries linked to hand preference We used meta-analyzed fMRI activation data from 14,371 studies, compiled within the Neurosynth database  (38) , to annotate our handedness-associated structural asymmetry maps with cognitive and behavioural functions (see Materials and Methods). We found that the clusters with altered average surface area asymmetries in left-handedness are especially activated by tasks involving executive functions, language and reading, mood and pain perception (Fig. 3  and Supplementary Table  3 ). The language-related annotations such as 'word, phonological, orthographic, reading, language' were likely contributed by the anterior insula and fusiform clusters in particular (Fig. 2 ): clusters 2 and 8 on the anterior insula, and cluster 1 on the fusiform cortex, overlap with regions previously identified as being conjointly and left-asymmetrically activated in each of the three sentence-level language task contrasts  (39).
From an independent set of 272,673 right-handed and 33,704 left-handed individuals in the UK Biobank, who were not overlapping and unrelated to those with brain image data, we derived effect sizes for the association of each SNP across the genome with hand preference (see Materials and Methods). We then applied these effect size estimates, in mass combination, to the 28,802 right-handed and 3,062 lefthanded individuals having genetic and brain imaging data for the present study, in order to quantify their polygenic dispositions to left-handedness, using the PRS-CS toolbox  (42). Polygenic disposition to lefthandedness was significantly associated with hand preference in this sample as expected (logistic regression beta=0. 12, p=6. 63×10 -5 ), as well as cerebral cortical surface area asymmetry within the fusiform cluster (r=-0.
Thus some specific handedness-related cortical asymmetries share genetic influences with hand preference, while others apparently do not, at least to extents that could be detected in the current sample size. In the adult cross-sectional data of the UK Biobank it is not possible to unambiguously establish causeeffect relations. Mediation models were compatible with fusiform and anterior insula surface area asymmetries partly mediating the effect of polygenic disposition on hand preference, but also with hand preference partly mediating the effect of polygenic disposition on these brain asymmetries. Both models are plausible, as brain anatomy may in principle be both causal to behavioural outcomes and shaped plastically by repeated behaviours, or indeed merely correlated due to shared underlying factors  (48).
The limitation of the UK Biobank cross-sectional data for making causal inferences from associations was already mentioned above. In addition, the UK Biobank is a volunteer cohort of middle-aged to older adults, and therefore not fully representative of the population, with generally superior health and socioeconomic circumstances for this age range, and greater female participation  (68). Higher risk for psychiatric disorders has been suggested to reduce participation in cohort studies (69), and we have previously found evidence for this in the UK Biobank  (70). In this study we linked genetic, brain structural and behavioural data, as well as making use of independent, meta-analyzed fMRI data to understand the functions of the implicated sets of cortical regions. Future studies of hand preference in large datasets may seek to integrate more aspects of brain structure and function from the same individuals into the analyses, including potentially resting-state fMRI and diffusion tensor imaging data on white matter structural connectivity.
Various other regional asymmetries associated with hand preference were not heritable, and may reflect plastic changes in support of hand preference, including those of primary sensorimotor cortex. Specific genes found to affect both hand preference and its cerebral cortical correlates include microtubule-related genes, one of which -NME7provides a potential mechanistic link between brain and visceral asymmetries which may not involve impaired ciliary function. This study provides an example of how linking across human genetics, brain structure and behavior in large datasets can provide tangible new knowledge, as well as mechanistic and developmental hypotheses for future research on typical and atypical human brain function.
Participants This study was conducted under UK Biobank application 16066, with Clyde Francks as principal investigator. The UK Biobank is a general adult population cohort  (72, 73). The UK Biobank received ethical approval from the National Research Ethics Service Committee North West-Haydock (reference 11/NW/0382), and all of their procedures were performed in accordance with the World Medical Association guidelines. Informed consent was obtained for all participants. Imaging-genetics dataset: We used the UK Biobank neuroimaging data  (74, 75)  released in February 2020, together with the genotype data from the same participants. To achieve a sufficiently high degree of homogeneity for the genetic analyses, we restricted the sample to participants with 'white British ancestry' defined by Bycroft et al.
We therefore excluded mixed handers and focused only on those indicating either right-or lefthandedness during their first visit. These steps resulted in a final sample of 31,864 participants, comprising 28,802 right-handers and 3,062 left-handers. The age range of these participants was from 45 to 81 years (mean 63. 75), and 15,064 were male, 16,800 female. Genome-wide screening dataset to obtain SNP-wise effect sizes for association with hand preference: These UK Biobank individuals had genetic and handedness data, but not brain image data. We applied the same genetic and handedness exclusion criteria as above, with the additional requirement that none of these individuals should have a kinship coefficient >0. 0442 with any of the individuals in the imaging-genetic data set. This yielded 272,673 right-handed and 33,704 left-handed participants, not overlapping and unrelated to the set with brain imaging data.
MRI processing Brain image data were derived from T1-weighted MRI scans (Siemens Skyra 3 Tesla MRI with 32channel radio frequency receive head coil). We started from the Freesurfer 6. 0 (77) 'recon-all' cortical reconstructions generated by the UK Biobank imaging team (UK Biobank data-field 20263, first imaging visit) -but did not make use of image-derived-phenotypes released by that team. Rather, the cortical thickness and surface area maps of both hemispheres of each individual were re-sampled into a standard symmetrical space created using inter-hemispheric co-registration (fsaverage_sym)  (34) , with 163,842 vertices per hemisphere (Supplementary Figure  4 ). This process required roughly 10 weeks of processing on 12 cluster server nodes running in parallel, and precisely aligned morphometry features between the two hemispheres to achieve vertex-wise correspondence.