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Circadian rhythms have received increasing attention within the context of mental disorders. Evening chronotype has been associated with enhanced risk to develop anxiety and post-traumatic stress disorder (PTSD). The classical fear conditioning paradigm is a powerful tool to reveal key mechanisms of anxiety and PTSD. We used this paradigm to study the neurocognitive basis of the association between chronotype and fear responses in healthy humans. 20 participants with evening chronotype and 20 controls (i.e., intermediate chronotype) completed a 2-day Pavlovian fear learning and extinction virtual reality task. Participants received fear conditioning, and extinction learning on day 1. Extinction memory recall was tested on day 2. To address interactions between chronotype and time of day of the fear conditioning, and extinction performance, half of the participants were tested in the morning, and the other half in the evening. Skin conductance response (SCR) and subjective fear ratings were measured as primary outcomes. Chronotype was established via the morningness-eveningness questionnaire (MEQ). We found an overall higher SCR for fear acquisition in participants with the evening chronotype profile, compared to controls. Moreover, the higher the MEQ scores -indicative of less eveningness - the lower the SCR was. No effects of chronotype were found for extinction and extinction recall. The higher vulnerability of the evening chronotype for anxiety and related disorders may thus be explained by enhanced fear acquisition of this group. [ABSTRACT FROM AUTHOR]

The popularity of mixed reality (MR) technologies, including virtual (VR) and augmented (AR) reality, have advanced many training and skill development applications. If successful, these technologies could be valuable for high-impact professional training, like medical operations or sports, where the physical resources could be limited or inaccessible. Despite MR's potential, it is still unclear whether repeatedly performing a task in MR would affect performance in the same or related tasks in the physical environment. To investigate this issue, participants executed a series of visually-guided manual pointing movements in the physical world before and after spending one hour in VR or AR performing similar movements. Results showed that, due to the MR headsets' intrinsic perceptual geometry, movements executed in VR were shorter and movements executed in AR were longer than the veridical Euclidean distance. Crucially, the sensorimotor bias in MR conditions also manifested in the subsequent post-test pointing task; participants transferring from VR initially undershoot whereas those from AR overshoot the target in the physical environment. These findings call for careful consideration of MR-based training because the exposure to MR may perturb the sensorimotor processes in the physical environment and negatively impact performance accuracy and transfer of training from MR to UR., (© 2024. The Author(s).)

Previous studies have shown that aerobic exercise has beneficial effects on executive function in adolescents with attention-deficit hyperactivity disorder (ADHD). The underlying mechanisms could be partially due to aerobic exercise-induced cortical excitability modulation. The aim of this study was to explore the effects of acute aerobic exercise on executive functions and cortical excitability and the association between these phenomena in adolescents with ADHD. The study was conducted using a complete crossover design. Executive functions (inhibitory control, working memory, and planning) and cortical excitability were assessed in twenty-four drug-naïve adolescents with ADHD before and after acute aerobic exercise or a control intervention. Inhibitory control, working memory, and planning improved after acute aerobic exercise in adolescents with ADHD. Moreover, cortical excitability monitored by transcranial magnetic stimulation (TMS) decreased after intervention in this population. Additionally, improvements in inhibitory control and working memory performance were associated with enhanced cortical inhibition. The findings provide indirect preliminary evidence for the assumption that changes in cortical excitability induced by aerobic exercise partially contribute to improvements in executive function in adolescents with ADHD., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Mixed reality technologies, such as virtual (VR) and augmented (AR) reality, present promising opportunities to advance education and professional training due to their adaptability to diverse contexts. Distortions in the perceived distance in such mediated conditions, however, are well documented and have imposed nontrivial challenges that complicate and limit transferring task performance in a virtual setting to the unmediated reality (UR). One potential source of the distance distortion is the vergence-accommodation conflict-the discrepancy between the depth specified by the eyes' accommodative state and the angle at which the eyes converge to fixate on a target. The present study involved the use of a manual pointing task in UR, VR, and AR to quantify the magnitude of the potential depth distortion in each modality. Conceptualizing the effect of vergence-accommodation offset as a constant offset to the vergence angle, a model was developed based on the stereoscopic viewing geometry. Different versions of the model were used to fit and predict the behavioral data for all modalities. Results confirmed the validity of the conceptualization of vergence-accommodation as a device-specific vergence offset, which predicted up to 66% of the variance in the data. The fitted parameters indicate that, due to the vergence-accommodation conflict, participants' vergence angle was driven outwards by approximately 0.2°, which disrupted the stereoscopic viewing geometry and produced distance distortion in VR and AR. The implications of this finding are discussed in the context of developing virtual environments that minimize the effect of depth distortion., Competing Interests: Conflict of interestThe authors have no conflicts of interest to declare that are relevant to the content of this article., (© The Author(s) 2024.)

Prevention of fatal side effects during cancer therapy of cancer patients with high-dosed pharmacological inhibitors is to date a major challenge. Moreover, the development of drug resistance poses severe problems for the treatment of patients with leukemia or solid tumors. Particularly drug-mediated dimerization of RAF kinases can be the cause of acquired resistance, also called "paradoxical activation." In the present work we re-analyzed the effects of different tyrosine kinase inhibitors (TKIs) on the proliferation, metabolic activity, and survival of the Imatinib-resistant, KIT V560G, D816V-expressing human mast cell (MC) leukemia (MCL) cell line HMC-1.2. We observed that low concentrations of the TKIs Nilotinib and Ponatinib resulted in enhanced proliferation, suggesting paradoxical activation of the MAPK pathway. Indeed, these TKIs caused BRAF-CRAF dimerization, resulting in ERK1/2 activation. The combination of Ponatinib with the MEK inhibitor Trametinib, at nanomolar concentrations, effectively suppressed HMC-1.2 proliferation, metabolic activity, and induced apoptotic cell death. Effectiveness of this drug combination was recapitulated in the human KIT D816V MC line ROSA KIT D816V and in KIT D816V hematopoietic progenitors obtained from patient-derived induced pluripotent stem cells (iPS cells) and systemic mastocytosis patient samples. In conclusion, mutated KIT-driven Imatinib resistance and possible TKI-induced paradoxical activation can be efficiently overcome by a low concentration Ponatinib and Trametinib co-treatment, potentially reducing the negative side effects associated with MCL therapy., (© 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

Purpose: Palliative radiotherapy for patients with head and neck cancer can be used to alleviate symptoms. Only a few studies have investigated its impact on patient-reported outcomes (PRO). Therefore, we conducted a prospective multicenter observational study. The primary objective was to assess changes in health-related quality of life (HrQoL) per PRO., Methods: Eligibility criteria included i.) head and neck cancer and ii.) palliative radiotherapy indicated (EQD 2Gy  < 60 Gy). The primary follow-up date was eight weeks after radiotherapy (t 8w ). PRO measures included the EORTC QLQ-C30 and EORTC QLQ-H&N43 and pain per Numeric Rating Scale (NRS). Per protocol, five PRO domains were to be reported in detail as well as PRO domains corresponding to a primary and secondary symptom as determined by the individual patient. We defined a minimal important difference (MID) of 10 points., Results: From 06/2020 to 06/2022, 61 patients were screened and 21 patients were included. Due to death or decline in health-status, HrQoL data was available for 18 patients at the first fraction and for eight patients at t 8w . The MID was not met for the predefined domains in terms of mean values as compared from first fraction to t 8w . Individually in those patients with available HrQoL data at t 8w , 71% (5/7) improved in their primary and 40% (2/5) in their secondary symptom domain reaching the MID from first fraction to t 8w , respectively. There was a significant improvement in pain per NRS in those patients with available data at t 8w per Wilcoxon signed rank test (p = 0.041). Acute mucositis of grade ≥3 per CTCAE v5.0 occurred in 44% (8/18) of the patients. The median overall survival was 11 months., Conclusion: Despite low patient numbers and risk of selection bias, our study shows some evidence of a benefit from palliative radiotherapy for head and neck cancer as measured by PRO.German Clinical Trial Registry identifier: DRKS00021197., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DK received honoraria from Merck Sharp & Dohme and Pfizer as well as research funding from Merck KGaA, outside of the submitted work. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Purpose: For patients with large tumors palliative radiotherapy often is the only local treatment option. To prevent toxicity the administered doses are low. Dose escalation to the tumor could be an option to better smyptom control and prolong local control rates. In this prospective study we used a very pragmatic approach with a simultaneously integrated boost (SIB) to an almost geometrically defined tumor core to achieve this. The primary endpoint was to demonstrate feasibility., Method: Patients with solid tumors > 4 cm in diameter of different histologies were eligible in this single arm, prospective, multi-institutional clinical feasibility trial with two treatment concepts: 5 × 5 Gy with an integrated boost to the tumor core of 5 × 10 Gy or 10 × 3 Gy with a boost of 10 × 6 Gy. The objective of dose escalation in this study was to deliver a minimum dose of 150% of the prescribed dose to the gross tumor volume (GTV) tumor core and to reach a maximum of at least 200% in the tumor core., Results: In all, 21 patients at three study sites were recruited between January 2019 and November 2020 and were almost evenly spread (9 to 12) between the two concepts. The treated planning target volumes (PTV) averaged 389.42 cm 3 (range 49.4-1179.6 cm 3 ). The corresponding core volumes were 72.85 cm 3 on average (range 4.21-338.3 cm 3 ). Dose escalation to the tumor core with mean doses of 167.7-207.7% related to the nonboost prescribed isodose led to PTV mean doses of 120.5-163.3%. Treatment delivery and short-term follow-up was successful in all patients., Conclusions: Palliative radiotherapy with SIB to the tumor core seems to be a feasible and well-tolerated treatment concept for large tumors. The applied high doses of up to 50 Gy in 5 fractions (or 60 Gy in 10 fractions) did not cause unexpected side effects in the 42 day follow-up period. Further research is needed for more information on efficacy and long-term toxicity., (© 2022. The Author(s).)

Tool-embodiment is said to occur when the representation of the body extends to incorporate the representation of a tool following goal-directed tool-use. The present study was designed to determine if tool-embodiment-like phenomenon emerges following different interventions. Participants completed body-part compatibility task in which they responded with foot or hand presses to colored targets presented on the foot or hand of a model, or on a rake held by the model. This response time (RT) task was performed before and after one of four interventions. In the Virtual-Tangible and the Virtual-Keyboard interventions, participants used customized controllers or keyboards, respectively, to move a virtual rake and ball around a course. Participants in the Tool-Perception intervention manually pointed to targets presented on static images of the virtual tool-use task. Participants in the Tool-Absent group completed math problems and were not exposed to a tool task. Results revealed that all four interventions lead to a pattern of pre-/post-intervention changes in RT thought to indicate the emergence of tool-embodiment. Overall, the study indicated that tool-embodiment can occur through repeated exposure to the body-part compatibility paradigm in the absence of any active tool-use, and that the paradigm may tap into more than just body schema.

Introduction: The persistence of post-detoxification problems in drug addiction is one of the disadvantages of the ultra-rapid opioid detoxification (UROD) method. Transcranial direct current stimulation (tDCS) has been introduced in experimental addiction treatment for some years. Results of pilot studies suggest that it might be a promising method for addiction treatment. This study explores the adjunctive application of tDCS during treating opiate addiction with the UROD approach., Methods: This double-blind, sham-controlled clinical trial was carried out on patients with substance abuse admitted to the Bahman Clinic of Yazd City in Iran (from March to September 2014). Forty participants were randomly allocated to treatment and control groups. Two sessions of tDCS (real or sham) over dorsolateral prefrontal cortices (DLPFC) were applied, accompanied by UROD. Withdrawal symptoms and craving were assessed by the drug desire questionnaire and objective opiate withdrawal scale before UROD and for the 24-hour interval after., Results: Transcranial direct current stimulation optimized the opiate addiction treatment through craving and withdrawal syndrome alleviation., Conclusion: The study results indicate that prefrontal tDCS may promote the efficacy of the UROD method in opioid addiction., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright© 2022 Iranian Neuroscience Society.)

Objective . Transcranial electrical stimulation (tES) is a promising method for modulating brain activity and excitability with variable results to date. To minimize electric (E-)field strength variability, we introduce the 2-sample prospective E-field dosing (2-SPED) approach, which uses E-field strengths induced by tES in a first population to individualize stimulation intensity in a second population. Approach . We performed E-field modeling of three common tES montages in 300 healthy younger adults. First, permutation analyses identified the sample size required to obtain a stable group average E-field in the primary motor cortex (M1), with stability being defined as the number of participants where all group-average E-field strengths ± standard deviation did not leave the population's 5-95 percentile range. Second, this stable group average was used to individualize tES intensity in a second independent population (n = 100). The impact of individualized versus fixed intensity tES on E-field strength variability was analyzed. Main results . In the first population, stable group average E-field strengths (V/m) in M1 were achieved at 74-85 participants, depending on the tES montage. Individualizing the stimulation intensity (mA) in the second population resulted in uniform M1 E-field strength (all p < 0.001) and significantly diminished peak cortical E-field strength variability (all p < 0.01), across all montages. Significance . 2-SPED is a feasible way to prospectively induce more uniform E-field strengths in a region of interest. Future studies might apply 2-SPED to investigate whether decreased E-field strength variability also results in decreased physiological and behavioral variability in response to tES., (Creative Commons Attribution license.)

Attention bias is a tendency to preferably detect, orient and select emotionally valued stimuli, as compared to neutral stimuli, and plays a crucial role in the psychopathology of various psychiatric disorders. Transcranial direct current stimulation (tDCS) has been applied for the alteration of attention bias in health and disease with different parameters and conditions, but the contribution of these factors to the magnitude and directionality of effects has not previously been comprehensively reviewed. In this review, we aimed to systematically explore the effects of tDCS on attention bias in different tasks, tDCS conditions, and health states. Data were collected in accordance with the PRISMA approach. A literature search identified 22 original experiments that explored the effects of tDCS on attention bias. Determinants of tDCS effects on attention bias were cortical target areas, the specific task under study, stimulation parameters, and the presence of psychopathology. Relevant cortical areas for modification of attention bias via tDCS were the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC). The observed heterogeneity of the impact of tDCS on the modulation of attention bias can be explained by the area of stimulation, valence of stimuli, task characteristics, and the intensity of stimulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

We report the case of an 11-year-old girl with difficultly speaking and a history of singular, self-limiting oral bleeding. Clinical and radiological examination in the emergency room showed a vascularized tumor of the base of the tongue, which almost completely occluded the oropharynx. After complex anesthesiologic preparation and endoluminal embolization, the tumor was safely removed by transoral laser microsurgery. Histology revealed a rare benign schwannoma of the oropharynx. Further clinical examinations and genetic screening were recommended., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Although a variety of theories have been proposed to explain the etiology of stuttering, the exact neurological origin of it is still uncertain. The aim of this study is to investigate the correlation between stuttering severity and ERP measures. The population of this study consisted of 12 adults with moderate, 12 adults with severe stuttering, and 12 fluent speakers as the control group. ERPs were recorded during an auditory task in which subjects should determine an oddball stimulus. The result of mismatch negativity (MMN) amplitude analysis revealed significant differences between severe stuttering and fluent speakers groups and between two stuttering groups. Moreover, the result showed significant differences between the three study groups for P300 amplitude. The findings of the present study suggest that the differences in ERP components are existed not only between people who stutter and fluent speakers but also between people with different levels of stuttering severity., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Stuttering is a disorder that begins in childhood and can persist into adulthood. In the present study, it was hypothesized that the combined intervention of transcranial direct current stimulation (tDCS) and Delayed Auditory Feedback (DAF) would cause greater improvement in speech fluency in comparison to the intervention with DAF alone., Methods: A randomized, double-blind, sham-controlled clinical trial was conducted to investigate the effects of the combined intervention. Fifty adults with moderate to severe stuttering (25 females, 25 males, Mean age=26.92, SD=6.23) were randomly allocated to the anodal or sham tDCS group. In the anodal tDCS group, participants received DAF combined with anodal tDCS (1 mA), while the sham tDCS group was exposed to sham tDCS simultaneously with DAF. In this study, a 60-ms delay was used for DAF intervention, and tDCS was applied over the left superior temporal gyrus. Each individual participated in six 20-minute intervention sessions (held on six consecutive days). Speech fluency was assessed before and after the intervention., Results: In the anodal tDCS group, the scores of the Stuttering Severity Instrument, Overall Assessment of the Speaker's Experience of Stuttering questionnaire, and the percentage of stuttered syllable reduced significantly (from average baseline rates of 8.45%, across three tasks, to 5.36% at the follow-up assessment) after the intervention., Conclusion: The results of this study suggest that delivery of anodal tDCS when combined with DAF may enhance stuttering reduction effects for six weeks following the intervention., (Copyright © 2022. Published by Elsevier Inc.)

Background: In the multimodal breast-conserving curative therapy of some high-risk breast cancer patients, extended external beam radiotherapy (EBRT) not only to the breast but also to the supraclavicular fossa and the internal mammary chain (parasternal region (PSR)) is indicated. We report a dosimetric study on the EBRT of the breast ("B") and the breast including PSR ("B + PSR"), comparing the supine and the laterally tilted prone patient positions in free breathing., Methods: The planning CT scans of 20 left- and 20 right-sided patients were analyzed. EBRT plans were calculated with 3D conformal EBRT (3D) and with intensity-modulated EBRT (IMRT) for "B" and "B + PSR" in the prone and supine positions. The mean and threshold doses were computed. The quality of EBRT plans was compared with an overall plan assessment factor (OPAF), comprising three subfactors, homogeneity, conformity, and radiogenic exposure of OAR., Results: In the EBRT of "B", prone positioning significantly reduced the exposure of the OARs "heart" and "ipsilateral lung" and "lymphatic regions". The OPAF was significantly better in the prone position, regardless of the planning technique or the treated breast side. In the EBRT of "B + PSR", supine positioning significantly reduced the OAR "heart" exposure but increased the dose to the OARs "ipsilateral lung" and "lymphatic regions". There were no significant differences for the OPAF, independent of the irradiated breast side. Only the IMRT planning technique increased the chance of a comparatively good EBRT plan., Conclusion: Free breathing prone positioning significantly improves plan quality in the EBRT of the breast but not in the EBRT of the breast + PSR.

Acute myeloid leukemia (AML) is a malignant disorder derived from neoplastic myeloid progenitor cells characterized by abnormal proliferation and differentiation. Although novel therapeutics have recently been introduced, AML remains a therapeutic challenge with insufficient cure rates. In the last years, immune-directed therapies such as chimeric antigen receptor (CAR)-T cells were introduced, which showed outstanding clinical activity against B-cell malignancies including acute lymphoblastic leukemia (ALL). However, the application of CAR-T cells appears to be challenging due to the enormous molecular heterogeneity of the disease and potential long-term suppression of hematopoiesis. Here we report on the generation of CD33-targeted CAR-modified natural killer (NK) cells by transduction of blood-derived primary NK cells using baboon envelope pseudotyped lentiviral vectors (BaEV-LVs). Transduced cells displayed stable CAR-expression, unimpeded proliferation, and increased cytotoxic activity against CD33-positive OCI-AML2 and primary AML cells in vitro. Furthermore, CD33-CAR-NK cells strongly reduced leukemic burden and prevented bone marrow engraftment of leukemic cells in OCI-AML2 xenograft mouse models without observable side effects., (© 2022. The Author(s).)

Background: Individuals with major depressive disorder (MDD) have deficits in emotion regulation, which plays a putative role in psychopathology. The ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are assumed to be involved in respective processes. In the present study, we aimed to explore the effect of stimulation over the dlPFC and vmPFC on emotion regulation in female with MDD., Material and Methods: Twenty women with MDD performed the Emotional Stroop, Emotional Go/No-Go, and Emotional 1-Back tasks during transcranial direct current stimulation (tDCS) in three separate sessions with the following electrode montages: anodal dlPFC (F3)/cathodal vmPFC (Fp2), anodal vmPFC (Fp2)/cathodal dlPFC (F3), and sham stimulation., Results: Independent of the valence of the respective stimuli, accuracy and speed of interference control, accuracy of pre-potent inhibition, and accuracy, but not speed, of working memory performance improved during anodal left dlPFC/cathodal right vmPFC stimulation. Independent of stimulation conditions, interference control was reduced for sad faces, as compared to happy and neutral faces, and working memory performance was faster for happy than for neutral and sad faces. For the impact of stimulation on specific emotional qualities, anodal left dlPFC/cathodal right vmPFC, compared to sham stimulation, led to improved interference control of sad and neutral faces in the emotional Stroop task, as shown by faster reaction times. Furthermore, in that task accuracy with respect to neutral and happy face conditions was higher during both real stimulation conditions, as compared to sham stimulation., Conclusion: The dlPFC is involved in emotion regulation in MDD. Emotional valence is moreover relevant for the effect of stimulation over this area on interference control in MDD., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The generation and expansion of functionally competent NK cells in vitro is of great interest for their application in immunotherapy of cancer. Since CD33 constitutes a promising target for immunotherapy of myeloid malignancies, NK cells expressing a CD33-specific chimeric antigen receptor (CAR) were generated. Unexpectedly, we noted that CD33-CAR NK cells could not be efficiently expanded in vitro due to a fratricide-like process in which CD33-CAR NK cells killed other CD33-CAR NK cells that had upregulated CD33 in culture. This upregulation was dependent on the stimulation protocol and encompassed up to 50% of NK cells including CD56 dim NK cells that do generally not express CD33 in vivo . RNAseq analysis revealed that upregulation of CD33 + NK cells was accompanied by a unique transcriptional signature combining features of canonical CD56 bright (CD117 high , CD16 low ) and CD56 dim NK cells (high expression of granzyme B and perforin). CD33 + NK cells exhibited significantly higher mobilization of cytotoxic granula and comparable levels of cytotoxicity against different leukemic target cells compared to the CD33 - subset. Moreover, CD33 + NK cells showed superior production of IFNγ and TNFα, whereas CD33 - NK cells exerted increased antibody-dependent cellular cytotoxicity (ADCC). In summary, the study delineates a novel functional divergence between NK cell subsets upon in vitro stimulation that is marked by CD33 expression. By choosing suitable stimulation protocols, it is possible to preferentially generate CD33 + NK cells combining efficient target cell killing and cytokine production, or alternatively CD33 - NK cells, which produce less cytokines but are more efficient in antibody-dependent applications., Competing Interests: CZ, MQ, MN, SC, RP, and NM are employees of Miltenyi Biotec. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hejazi, Zhang, Bennstein, Balz, Reusing, Quadflieg, Hoerster, Heinrichs, Hanenberg, Oberbeck, Nitsche, Cramer, Pfeifer, Oberoi, Rühl, Oldenburg, Brossart, Horn, Babor, Wels, Fischer, Möker and Uhrberg.)

Background: and purpose of the study: Individuals with general anxiety disorder (GAD) have deficits in emotional and cognitive processing, including cognitive bias, which plays a causal role in anxiety. Hyperactivity of the ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) is assumed to be involved in cognitive bias. We aimed to explore the causal contribution of the dorsolateral and ventromedial prefrontal cortices (dlPFC, vmPFC) on cognitive bias via non-invasive brain stimulation, and expected a bias-reducing effect of cortical activity enhancement over these areas in GAD, with a larger contribution of the vmPFC to perceptual, and of the dlPFC to interpretation bias., Material and Methods: The study was conducted in a randomized, single-blinded, and complete crossover design. Thirty-four adults with GAD, received transcranial direct current stimulation (tDCS) in 5 separate sessions (1.5 mA, 20 min) with the following electrode montages: anodal dlPFC/cathodal vmPFC, anodal vmPFC/cathodal dlPFC, anodal dlPFC/cathodal right shoulder, anodal vmPFC/cathodal left shoulder, and sham stimulation. During stimulation, in each session, participants performed the Dot-Probe and Reading Mind from Eyes tests to measure attention and interpretation biases., Results: A significant effect of stimulation condition on attention and interpretation biases was observed. Anodal vmPFC and dlPFC stimulation coupled with an extracranial cathodal electrode reduced attention bias to threat-related stimuli in the dot-probe test. Furthermore, anodal dlPFC/cathodal vmPFC stimulation reduced negative interpretation bias in reading from eyes test., Conclusion: As suggested by the results of this study, both dlPFC and vmPFC are involved in cognitive bias in GAD, but with partially different roles. Anodal stimulation over the right vmPFC and the left dlPFC reduced attention bias, supporting the relevance of these areas for attention bias. For interpretation bias, the significant effect of anodal dlPFC/cathodal vmPFC stimulation, but only trendwise effect of anodal tDCS over the dlPFC combined with an extracephalic return electrode is in accordance with a predominant effect of the dlPFC on interpretation bias, but does not rule out an additional minor involvement of the vmPFC. Based on these results, a new model is suggested for the neural underpinnings of anxiety symptoms., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Retrospective studies have described the effectiveness of low-dose radiotherapy (LD-EBRT) in painful arthrosis of small finger joints, but two recent prospective studies have yielded ambiguous results. To generate accurate data for the planning of a trial, we conducted a prospective, monocentric, observational study to describe the effects of LD-EBRT as precisely as possible. Methods : Twenty-five consecutive patients with symptomatic trapeziometacarpal (TMC) arthrosis were irradiated with 6 × 0.5 Gy. Before, 3, and 12 months after LD-EBRT, we assessed subjective endpoints (modified "von-Pannewitz score", 10-point visual analogue scale (VAS), "patient-rated wrist evaluation" (PRWE)), and objective measurements ("active range of motion" (AROM), Kapandji index, grip strength, pinch grip). Results : At 3/12 months, 80%/57% reported partial and 4%/18% complete remission according to the "von-Pannewitz" score. VAS "overall pain" significantly decreased from a median of seven (IQR 4) at baseline to three (IQR 6; p = 0.046) and to two (IQR 2; p = 0.013). Similar results were obtained for VAS "pain during exercise", VAS "pain during daytime", and VAS "function". "PRWE overall score" was reduced from 0.5 at baseline (SD 0.19) to 0.36 (SD 0.24, p = 0.05) and to 0.27 (SD 0.18, p = 0.0009). We found no improvements of the objective endpoints (AROM, Kapandji, grip strength) except for flexion, which increased from 64° (SD 12°) at baseline to 73° (SD 9.7°, p = 0.046) at 12 months. Conclusions: We recommend the PRWE score as a useful endpoint for further studies for this indication. To prove a 15% superiority over sham irradiation, we calculated that 750 patients need to be prospectively randomized.