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Single versus combination treatment in tinnitus: an international, multicentre, parallel-arm, superiority, randomised controlled trial
No full textTinnitus is defined as the conscious awareness of a tonal or composite noise in the absence of a corresponding external acoustic source. This international multicentre, parallel-arm, superiority, randomised controlled trial investigated whether combination therapies are superior to single interventions in the treatment of chronic subjective tinnitus. Tinnitus patients were recruited from five clinical sites across the EU and randomly assigned using a web-based system, stratified by their hearing and distress level, to single or combination treatment of 12 weeks. Cognitive-behavioural therapy, hearing aids, app-based structured counselling, or app-based sound therapy were administered either alone or as a combination of two treatments resulting in ten treatment arms. App-based treatments were delivered without direct contact or guidance from clinicians. The primary outcome was the difference in the change from baseline to week 12 in the total score of the Tinnitus Handicap Inventory (THI) between single and combination treatments in the intention-to-treat population. All statistical analysis were performed blinded to treatment allocation. 674 patients of both sexes aged between 18 and 80 years were screened for eligibility. 461 participants (190 females) with chronic subjective tinnitus and at least mild tinnitus handicap were enroled, 230 of which were randomly assigned to single and 231 to combination treatment. Least-squares mean changes from baseline to week 12 were −11.7 for single treatment (95% confidence interval [CI], −14.4 to −9.0) and −14.9 for combination treatments (95% CI, −17.7 to −12.1), with a statistically significant group difference (p = 0.034). Cognitive-behavioural therapy and hearing aids alone had large effect sizes, which could not be further increased by combination treatment. No serious adverse events occurred. In this trial involving patients with chronic tinnitus, all treatment arms showed improvement in THI scores from baseline to week 12. Combination treatments showed a stronger clinical effect than single treatment, however, no clear synergistic effect was observed when combining treatments. Instead, we observed a compensatory effect, where a more effective treatment offsets the clinical effects of a less effective treatment. ClinicalTrials.gov Identifier: NCT04663828
Characterisation of a university student sample with a lifetime history of non-suicidal self-injury: mixed-methods analysis of stress factors, coping mechanisms and reasons for self-injury
No full textBackground
Non-suicidal self-injury (NSSI) displays an alarmingly high
prevalence rate among university students, placing them at high
risk for adverse long-term outcomes, including suicide.
Aims
This study aimed to achieve a better understanding of factors
contributing to NSSI in university student populations by
examining reasons for NSSI and histories of stressful events and
coping strategies.
Method
A total of 185 university students with a lifetime history of NSSI
were assessed for depressive symptoms and NSSI characteristics.
They completed three questionnaires on NSSI reasons,
stressful events and coping strategies during childhood and
adolescence. Each questionnaire included an ‘others’ option
combined with an open-ended response box. After descriptive
analysis of the closed questions, these open-ended responses
were qualitatively categorised and analysed as predictors of
depression severity and NSSI continuation from adolescence
into adulthood.
Results
Qualitative analysis identified eight, five and ten categories from
the open-ended responses for NSSI reasons, stressful events
and coping strategies, respectively, with substantial to almost
perfect interrater reliability. Two qualitative reason categories,
one stressful event category and two coping strategy categories
significantly predicted depression severity (β = 0.21–0.23).
Participants reporting events in the stressful events category
‘Traumatisation and experiences of violence’ were three times
more likely to continue NSSI into adulthood (f 2 = 0.07).
Conclusions
This study demonstrates the value of mixed-methods
approaches. Stable qualitative categories highlight the need to
capture individual variations in NSSI-related factors. It emphasises
trauma-related stressors due to their influence on
depression severity and persistence of NSSI into adulthood
Machine Learning-Identified Potent Antimicrobial Peptides Against Multidrug-Resistant Bacteria and Skin Infections
No full textBackground: The escalating global crisis of antibiotic resistance necessitates the discovery of novel antimicrobial agents. Antimicrobial peptides (AMPs) represent a promising alternative to combat multidrug-resistant (MDR) pathogens. Because traditional AMP discovery is labour-intensive and costly, machine learning (ML) is applied to identify AMPs effective against MDR bacteria and skin infections. Methods: The ML-based CalcAMP model predicts the antimicrobial activity of 16,384 unique 14-amino-acid peptide sequences, resulting in a novel Guided Designed Smart antimicrobial Therapeutic (GDST) peptide catalogue. Parent sequences and retro-inverso (RI) variants of two prime GDST peptides undergo extensive testing against MDR bacteria and in skin infection models. Results: GDST-038 and GDST-045, along with their RI variants, show potent antimicrobial activity against Acinetobacter baumannii and Staphylococcus aureus, rapidly depolarizing the cytoplasmic membrane, exhibiting broad-spectrum bactericidal effects against ESKAPE pathogens, and causing minimal haemolysis. RI variants display superior A. baumannii biofilm killing compared to parent sequences, while all GDST peptides achieve >3-log reductions in S. aureus biofilm CFU within 24 h. Potent efficacy is observed in a 3D human skin epidermal infection model, with elimination of S. aureus at ≥15 μM. No resistance develops after 22 passages. Conclusions: ML-driven screening enables rapid identification of two novel candidate AMPs, highlighting the therapeutic potential of GDST peptides for MDR bacterial infections
Case Report: Nirogacestat therapy induces rapid response in a patient with refractory, life-threatening desmoid tumor
No full textBackground: Desmoid tumor (DT) is a rare soft tissue neoplasm characterized by locally aggressive infiltration into adjacent tissues with few established treatment regimens. So far, the evidence-based therapeutic arsenal for DT has comprised surgery, locoregional therapy, tyrosine kinase inhibitor treatment, and chemotherapy. The γ-secretase inhibitor nirogacestat was approved by the FDA in 2023 and, in 2025, received European authorization as the first and only agent for treatment of progressive DT requiring systemic therapy predicated on positive results from an international phase 3 clinical trial.
Methods: Single case study and review of the literature.
Case presentation: We report on a 29-year-old patient with a recurrent DT located below the right mastoid process with extensive infiltration into cervical tissue and compression of the right internal jugular vein. Following early relapse to surgery, the patient sequentially failed treatment with pegylated liposomal doxorubicin (PLD), sorafenib, and a combination of doxorubicin and dacarbazine. Against the backdrop of life-threatening circumstances due to pending infiltration of the right carotid artery, the patient was subjected to nirogacestat treatment as part of a compassionate use program. Upon four months of nirogacestat treatment, MRI-imaging revealed a sizable regression of the DT, substantially decreasing the danger of carotid artery infiltration. Currently, the patient continues nirogacestat treatment, and no severe side effects were observed.
Conclusion: Albeit rarely lethal in general, DT can exert life-threatening danger by local infiltration into vital tissue, such as blood vessels. The presented case highlights the novel γ-secretase inhibitor nirogacestat as a highly effective therapy preventing infiltration of the right carotid artery by a remarkably refractory DT
Regensburger Energie-Tagebuch
No full textDas multiFACE-Projekt untersucht chronische Fatigue aus neuropsychologischer und kognitiv-verhaltenstherapeutischer Perspektive und berücksichtigt dabei körperliche, kognitive und emotionale Dimensionen der Fatigue und Fatigability. Es basiert auf dem Verständnis, dass chronische Fatigue / Minderbelastbarkeit ein heterogenes Phänomen ist, das in verschiedenen Gesundheitsbedingungen auftreten kann, und entwickelt multidimensionale Ansätze zur Erfassung und Intervention.
Für eine Fortführung des Projekts multiFACE wurde ein Energietagebuch erstellt, das die tägliche Erfassung körperlicher, emotionaler und kognitiver Energielevels ermöglicht. Die Teilnehmer*innen dokumentieren ihr tägliches Energielevel auf einer Skala von 0 bis 10 (0 = keine Energie; 10 = gesundes Energieniveau wie vor der Erkrankung) und halten relevante Besonderheiten fest, einschließlich emotionaler Ereignisse, körperlicher Aktivität, kognitiv anspruchsvoller Aufgaben, Krankheit oder Erholungsphasen. Zusätzlich wird die tägliche Aktivitätszeit (z. B. Arbeits- oder Schulzeit) eingetragen, um Zusammenhänge zwischen Belastung und Energieverlauf sichtbar zu machen.
Am Ende jeder Woche werden die Werte mittels farbigen Kreuzchen (Körperlich: grau, Kognitiv: blau, Emotional: rot und Aktivitätszeit: schwarz)) in eine grafische Übersicht übertragen. Das Verbinden der Kreuzchen ermöglicht die Abbildung von Trends über die verschieden-farbigen Energielevels und Aktivitätszeiten.
Ein zweites Arbeitsblatt dient dazu, die wöchentlichen Durchschnittswerte über einen Zeitraum von 12 Wochen systematisch zu erfassen. Hier werden die Mittelwerte der körperlichen, kognitiven und emotionalen Energielevel sowie die wöchentliche Aktivitätszeit eingetragen. Dieses Vorgehen ermöglicht eine strukturierte, longitudinal nachvollziehbare Darstellung individueller Energieverläufe und unterstützt die Analyse kurz- und mittelfristiger Veränderungen über alle drei Energieebenen hinweg
Data set of publication "Structural remodeling of the mitochondrial protein 1 biogenesis machinery under proteostatic stress"
No full textKryptografisches Vermögen und der Erbfall - Eine Grundlagenanalyse der Theorie und Praxis anhand der derzeitigen technologischen Standards
No full textDie Arbeit behandelt die Frage der Vererbbarkeit kryptografischen Vermögens und die Handhabe von Kryptovermögen in Testamenten und anderen Verfügungen von Todes wegen.
Die Arbeit befasst sich insbesondere mit
1. den technischen Grundlagen des Kryptovermögens,
2. der Frage nach dem Anknüpfungsobjekt der Vererbbarkeit bei Kryptovermögen und
3. dem Umgang mit dem Kryptonachlass anhand der Gestaltungsmittel des Bürgerlichen Gesetzbuches
Dataset to "Quantum Chaos as an Essential Resource for Full Quantum State Controllability"
No full textDataset to the publication "Quantum Chaos as an Essential Resource for Full Quantum State Controllability"
The dataset contains relevant numerical raw data to reproduce the figures in the publication