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Near-infrared (NIR) photothermal conversion materials have recently received widespread attention due to their potential in diverse applications. However, highly efficient organic-based NIR photothermal agents remain limited. Developing strategies to enhance the efficiency of NIR photothermal materials and elucidating the relationship between the NIR photothermal performance and molecular aggregation are highly desired. Herein, we report two coordination polymers {[Cd 2 (ONDI)(ox)]·2/3(H 2 O)} n ( 1 ) and [Ba(ONDI)(H 2 O) 2 ] n ( 2 ), in which the ONDI 2- ligands assemble into different π-π stacking arrangements. Compound 1 exhibits H-aggregation, while compound 2 displays X-aggregation. The X-aggregation in compound 2 extends the optical absorption into the NIR region and enhances the absorption intensity. Consequently, compound 2 demonstrates a 1.8-fold increase in NIR photothermal efficiency (68.6%) compared to compound 1 (38.8%), attributed to more effective π-π interactions in X-aggregation. In addition, both compounds show semiconductive properties, with conductivities of 2.1 × 10 -7 S/cm for compound 1 and 3.0 × 10 -7 S/cm for compound 2 at 30 °C in a nitrogen atmosphere. These properties arise from the synergistic effects of "band-like" charge transport within crystals and "hopping" charge transport across grain boundaries. By integration of their NIR photothermal effects and semiconductive properties, compounds 1 and 2 show interesting NIR photoelectrical responses.

Commercial SSZ-13 zeolite with different n(Si)/n(Al) ratios and from different suppliers were subjected to a post-synthetic treatment in order to create mesopores of up to 15 nm. Furthermore, the materials were modified with copper ions and thoroughly physico-chemically characterized. The modified textural properties varied the nature of copper species, and thus, activity in the selective catalytic reduction of NO x with ammonia (NH 3 -SCR-DeNO x ). Pulsed-field gradient nuclear magnetic resonance (PFG-NMR) studies with hexane as probe liquid revealed improved intracrystalline diffusion for some Cu-containing SSZ-13 materials. The NH 3 -SCR-DeNO x pathways are verified via in situ DR UV-Vis, in situ FT-IR and EPR, temperature-programmed studies as well as SSITKA studies that provide a mechanistic understanding of the reaction. Kinetic modelling results demonstrate the highest NH 3 -SCR-DeNO x reaction rates and up to 20 % lower energy barriers with n(Si)/n(Al) ratio of 6.5 for all modified forms (i. e., (NH 4 )Cu-SSZ-13_6.5 and Cu-SSZ-13_6.5_NaOH/0.1) and cause only negligible parasitic ammonia oxidation. The modelling of the stop-flow experiments further demonstrates that the SCR pathway via the HONO surface intermediate is present but barely contributes to the overall NO conversion compared to the dominant path between adsorbed NH 3 and NO from the gas phase., (© 2024 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Due to its high sensitivity and high negative predictive value, computed tomography angiography of the coronary arteries (CCTA) has proven to be particularly useful for ruling out obstructive coronary artery disease (CAD) in cases of suspected chronic coronary syndrome (CCS), which is why CCTA will also be included in the care of patients with statutory health insurance in Germany according to the G-BA decision of January 24, 2024. The value of CCTA is clearly confirmed in the current guidelines of the European Society of Cardiology (ESC) and the national care guideline from August 2024. However, good results from CCTA can only be achieved-in addition to appropriate qualifications of those performing the test and the necessary technical requirements-if the right patients are included, namely those with a low intermediate pretest probability for the presence of obstructive CAD. For this purpose, the pretest probability (PTP) for the presence of obstructive CAD must be determined before the indication is established. As it is not yet clear which method should be used for this purpose, this overview presents various methods for calculating the PTP for the presence of obstructive CAD. In the latest methods of the ESC Guideline 2024, cardiovascular risk factors, previous findings or the calcium score are included in the calculation in addition to age, gender and symptoms, which increases the accuracy of the prediction. The advantages and disadvantages of the various methods are explained using case studies., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Photosynthetic reaction centers (RCs) serve as natural engines converting solar energy to chemical energy. Understanding the principles of efficient charge separation and light-induced electron transfer (ET) between the chlorophyll-type pigments might guide the synthesis for artificial photosynthetic systems. We present detailed insight into the dynamics at the atomic level using solid-state NMR techniques applied to the RCs of Heliobacillus (Hb.) mobilis (HbRCs) and the purple bacterium Rhodobacter (R.) sphaeroides (PbRCs). It is assumed that heliobacteria were among the first phototrophic organisms; therefore, their RC can be regarded as ancient. They are constructed homodimerically with perfect C 2 symmetry, enabling ET over both branches of cofactors. Modern RCs of R. sphaeroides wild-type (WT) have higher redox power and are functionally highly asymmetric. The dynamics of the cofactors in both RCs has been explored using nuclear hyperpolarization, induced by the solid-state photochemically induced dynamic nuclear polarization (photo-CIDNP) effect. Based on the individual incorporation of 13 C positions of the cofactors (through supplementation by 13 C-δ-aminolevulinic acid), photo-CIDNP magic-angle spinning (MAS) NMR experiments provide access to the local dynamics of the cofactors along the ET path over a broad range of time scales. Theoretical analysis of the dynamic deformation of these macrocycles is also discussed in terms of function. The dynamics observed in HbRCs appears to be correlated to ET. The cofactors in PbRC are significantly less dynamic than those in the HbRC. Relevance for efficiency and redox properties are discussed.

Objective: People with mental illness should live independently in the community. This study analyzed the housing situation and the use and need of psychiatric housing facilities of people with severe mental illness., Methods: Data from a cross-sectional study with 397 people with severe mental illness from two Bavarian districts were used and analyzed descriptively., Results: 70% of the patients live independently. 6% use supported housing or residential care. 25% of the participants have housing needs, but 39% of them do not receive adequate help. Most of the patients are familiar with supported housing or residential care and find these helpful., Conclusion: Most patients live in a housing situation that meets the social norm. However, some patients have an unresolved housing problem. The use of supported housing or residential care is helpful, but is rarely used., Competing Interests: Alkomiet Hasan erhielt Vortragshonorare von AbbVie, Advanz, Janssen, Otsuka, Rovi, Recordati und Lundbeck. Er war Mitglied in Advisory Boards für Boehringer-Ingelheim, Janssen, Otsuka, Rovi, Recordati und Lundbeck. Einladungen zu Kongressen oder Essen wurden nicht angenommen. Er ist Herausgeber der AWMF S3-Leitlinie Schizophrenie, Angestellter des Freistaats Bayern und der Bezirkskliniken Schwaben. Karel Frasch hat Kongressreiseunterstützungen von Janssen erhalten. Er ist stellv. Sprecher von ackpa und Mitglied im Vorstand der DGPPN. Alle anderen Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Insects process their food with their cuticle-based mouthparts. These feeding structures reflect their diversity and can, in some cases, showcase adaptations in material composition, mechanical properties, and shape to suit their specific dietary preferences. To pave the way to deeply understand the interaction between mouthparts and food and to determine potential adaptations of the structures to the food, this study focuses on the mandibles of two praying mantis species. Gongylus gongylodes feeds mainly on Diptera, and Sphodromantis lineola forages on larger prey. Employing scanning electron microscopy, the mandibular morphologies were analyzed. The degree of the cuticle tanning was tested using confocal laser scanning microscopy. Furthermore, the contents of transition and alkaline earth metals in the mandible cuticle were studied using energy-dispersive X-ray spectroscopy and the mechanical properties tested by nanoindentation. We found that S. lineola mandibles show pronounced gradients of Young's modulus and hardness from the basis to the tip, which might be an adaptation against high stresses during biting and chewing. G. gongylodes, in contrast, did not show pronounced gradients, which may indicate that there is less stress involved in feeding-necessary to test in future studies. The mechanical properties of manidibles in both species are related to the degree of cuticle tanning but also positively correlate with the content of magnesium. These findings enrich our understanding of insect cuticle biology but also present new sets of data on praying mantis structures., (© 2024 The Author(s). The Anatomical Record published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Child abuse increases the risk of adult mental health problems. Limited research explores the association of early institutional childhood care in the GDR with experienced childhood abuse and mediates anxiety and depression in adulthood. The sample includes N=1743 individuals born in the GDR (1949-1983). In multi-group path analyses (stratified men/women), we analysed the influence of pre-school care as a predictor and experienced child abuse (CTS) as a mediator variable for anxiety (GAD-7) and depression (PHQ-9) in adulthood. There are no direct effects of pre-school care on anxiety and depression. Childhood trauma significantly affected current mental health (women β=0.253-0.610; men β=0.092-0.439). Analyses suggest no link between early institutional care and childhood abuse. Considering other contextual factors in childcare is crucial for establishing population-wide prevention strategies for child safety., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Objective: Currently, there is an intensive discussion on advancing and expanding outpatient rhinosurgical procedures. Many questions about how to stratify into out- and inpatient procedures are still not sufficiently clarified. Particularly, the use of nasal packing materials is not adequately discussed., Material and Methods: Development of a checklist to stratify sinunasal procedures into in- or outpatient procedures with consideration of current scientific literature and risk factors., Results and Conclusions: After comprehensive assessment of the literature and analysis of specific risk factors, a list of sinunasal procedures is presented, which should be performed as inpatient procedures. We present a checklist for in- and outpatient sinunasal procedures, which considers social, medical and surgical factors as well as the use of nasal packing materials. Furthermore, a checklist is added to assess, whether patients are ready for discharge after a planned outpatient procedure., Competing Interests: Rainer Weber: Empfang von Honoraren oder Beratungsgebühren: GSK, Hommel Pharma, Infectopharm, KARL STORZ, Sanofi-Aventis, Sidroga, Spiggle & Theis, Stryker Bernhard Olzowy: Vortragshonorare für Radiofrequenzchirurgiekurse seitens der Fa. Neuwirth Medical Products, die selbstauflösende Chitosantamponaden (PosisepX) vertreibt. Frank Haubner: Honorare für Vorträge bei folgenden Firmen: Brainlab, Spiggle&Theis, RG Ärzteberatung, Neuwirth Robert Böscke: Reisekosten, Vortragshonorare: Sanofi, GSK Achim Beule: Vorträge für AstraZeneca, GlaxoSmithKline, Happersberger otopront, Medtronic, Novartis, Sanofi Aventis, Xion; Beratertätigkeit für AstraZeneca, GlaxoSmithKline, Medtronic, Novartis, Sanofi Aventis, Durchführung von wissenschaftlichen Studien an der Uniklinik Münster für Allakos, AstraZeneca, BioMed Elements/EU, Bristol Myers Squibb, GlaxoSmithKline, Happersberger otopront/AiF,Sanofi Aventis, Winicker Norimed; insgesamt aber keine Tätigkeiten mit Schwerpunkt „Nasentamponaden“ oder mit Bezug zu dieser Publikation Thomas Kühnel: Glaxo Smith Kline: Advisory Board; Karl Storz Endoskope: bezahlte Tätigkeit bei Operationskursen; Sanofi: Advisory Board (Einladung), Vortragstätigkeit; Dt. Fachgesellschaft für HNO-Heilkunde, Kopf- und Halschirurgie; Dt. Fachgesellschaft für Schädelbasischirurgie, (Thieme. All rights reserved.)

Objective: Currently, there is an intensive discussion about enhancing and expanding outpatient rhinosurgical procedures. Many questions about how to stratify into out- and inpatient procedures are still not sufficiently clarified. Particularly, the use of nasal packing materials is not adequately discussed., Material and Methods: We performed a Germany-wide survey among otorhinolaryngologists regarding the use of nasal packing materials in sinonasal surgery. Additionally, we asked for any complication in relation to nasal packing., Results: In 85,6% nasal packing was used for septal and turbinate surgery at least occasionally, in 44,2% always. In sinus surgery these numbers are 94,1% and 49%, respectively. Non-resorbable nasal packing materials were predominantly used.Most frequent complications were bleeding with nasal packing in situ (> 50% of respondents) and posterior dislocation (24% of respondents), requiring emergency treatment. Death was listed in 5 patients. One patient suffered from permanent brain damage due to hypoxia., Conclusions: Application of non-resorbable nasal packing materials with occlusion of the nasal cavity carry a substantial risk of complications, which necessitate emergency treatment, thus requiring inpatient care., Competing Interests: Rainer Weber: Empfang von Honoraren oder Beratungsgebühren: GSK, Hommel Pharma, Infectopharm, KARL STORZ, Sanofi-Aventis, Sidroga, Spiggle & Theis, Stryker. Bernhard Olzowy: Vortragshonorare für Radiofrequenzchirurgiekurse seitens der Fa. Neuwirth Medical Products, die selbstauflösende Chitosantamponaden (PosisepX) vertreibt. Frank Haubner: Honorare für Vorträge bei folgenden Firmen: Brainlab, Spiggle&Theis, Neuwirth, RG Ärzteberatung. Robert Böscke: Reisekostenerstattungen: Sanofi, GSK, Allergopharma, MedEL, Cochlear; Vortragshonorare: Sanofi, GSK Achim Beule: Vorträge für AstraZeneca, GlaxoSmithKline, Happersberger otopront, Medtronic, Novartis, Sanofi Aventis, Xion; Beratertätigkeit für AstraZeneca, GlaxoSmithKline, Medtronic, Novartis, Sanofi Aventis, Durchführung von wissenschaftlichen Studien an der Uniklinik Münster für Allakos, AstraZeneca, BioMed Elements/EU, Bristol Myers Squibb, GlaxoSmithKline, Happersberger otopront/AiF,Sanofi Aventis, Winicker Norimed; insgesamt aber keine Tätigkeiten mit Schwerpunkt „Nasentamponaden“ oder mit Bezug zu dieser Publikation Thomas Kühnel: Glaxo Smith Kline: Advisory Board; Karl Storz Endoskope: bezahlte Tätigkeit bei Operationskursen; Sanofi: Advisory Board (Einladung), Vortragstätigkeit; Dt. Fachgesellschaft für HNO-Heilkunde, Kopf- und Halschirurgie; Dt. Fachgesellschaft für Schädelbasischirurgie, (Thieme. All rights reserved.)

Objective of the Study: To investigate the importance of individual topics in outpatient care services and the preferences for their design from the perspective of young adults with cancer (AYA="adolescents and young adults") in Germany., Methodology: A total of 514 AYAs aged 18-39 years were surveyed twice over a 12-month period (t1=immediately after acute treatment, t2=12 months post-treatment) regarding the importance and satisfaction with topics such as anxiety, the impact of the illness on partnerships/family and social environment, future perspectives, personal coping strategies, sexuality, and desire for children/fertility, as well as the types of care services. The subjective importance and satisfaction with the care topics and services were analyzed using variance and moderator analyses., Results: The most important topics for care services were future career prospects (M=3.22, SD=1.56), social impact (M=3.19, SD=1.54), and personal coping strategies (M=3.52, SD=1.46). The greatest dissatisfaction was noted in the areas of sexuality (M=2.01, SD=1.59) and desire for children/fertility (M=2.08, SD=1.72). At time t2, relaxation techniques (M=3.46, SD=1.36) and psychological counseling (M=3.43, SD=1.46) were the most desired care services. Female AYAs rated psychological counseling (F[1.199)=9.21, p=0.003), social counseling (F[1.221]=6.60, p=0.011), creative therapy options (F[1.219]=21.74, p<0.001), support groups (F[1.215]=4.29, p=0.040), patient education (F[1.210]=6.96, p=0.009), and relaxation techniques (F[1.194]=23.68, p<0.001) significantly more important than male AYAs., Conclusions: The study highlighted several areas of dissatisfaction with the current outpatient care services for AYAs. The results demonstrate the need to incorporate cross-sex and gender-specific care preferences of AYAs to improve outpatient psychosocial care. A specific set of AYA-care services should be designed and implemented to address the aforementioned psychosocial topics, which include sexuality and the desire for children/fertility. It is also crucial for outpatient practice to raise awareness among the involved professional groups. Further research is required to gain a deeper understanding of sex differences., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Study Question: What is the impact of the EuroNet-PHL-C2 treatment for boys with classical Hodgkin lymphoma (cHL) on semen parameters?, Summary Answer: More than half of the patients (52%, n = 16/31) had oligozoospermia or azoospermia at 2 years from cHL diagnosis; particularly boys treated for advanced-stage cHL had low sperm counts and motility., What Is Known Already: Chemotherapy and radiotherapy to the inguinal region or testes can impair spermatogenesis and result in reduced fertility. The EuroNet-PHL-C2 trial aims to minimize radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. The present study aims to assess the (gonadotoxic) impact of this treatment protocol on semen parameters and reproductive hormones in boys aged ≤18 years., Study Design, Size, Duration: This international, prospective, multi-centre cohort study was an add-on study to the randomized phase-3 EuroNet-PHL-C2 trial, where the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) was compared to intensified OEPA-DECOPDAC-21 chemotherapy (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide). Patients were recruited between January 2017 and September 2021., Participants/materials, Setting, Methods: Eligibility criteria included male patients, diagnosed with classical HL before or at the age of 18 years, and treated according to the EuroNet-PHL-C2 protocol in any of the 18 participating sites in the Netherlands, Germany, Belgium, Czech Republic, and Austria. Sperm parameters (sperm concentration, progressive motility, sperm volume, and calculated total motile sperm count) were assessed at diagnosis and 2 years after diagnosis in (post)pubertal boys. Laboratory measurements (serum follicle-stimulating hormone (FSH) and inhibin B) were performed in samples drawn at diagnosis, during treatment (2-3 times), and at 2 years post-diagnosis, and (age-adjusted) analyses were conducted separately for pre-pubertal and (post)pubertal boys. Outcomes were compared between the treatment levels (TL1, TL2, and TL3) and consolidation treatment schemes (COPDAC-28 and DECOPDAC-21)., Main Results and the Role of Chance: In total, 101 boys were included in the present analysis: 73 were (post)pubertal (median age 15.4 years, (IQR 14.4; 16.6), 10 TL1, 29 TL2, 34 TL3, 62% of TL2/3 patients received COPDAC-28) and 28 boys were pre-pubertal (median age 9.6 years (IQR 6.6; 11.4), 4 TL1, 7 TL2, 17 TL3, 38% of TL2/3 patients received COPDAC-28). The study included six boys who had received pelvic radiotherapy; none were irradiated in the inguinal or testicular area. At diagnosis, 48 (post)pubertal boys delivered semen for cryopreservation; 19 (40%) semen samples were oligospermic and 4 (8%) were azoospermic. Low sperm concentration (<15 mil/ml) appeared to be related to the HL disease itself, with a higher prevalence in boys who presented with B symptoms (76% vs 26%, aOR 2.3 (95% CI 1.0; 3.8), P = 0.001) compared to those without such symptoms. At 2 -years post-diagnosis, 31 boys provided semen samples for analysis, of whom 12 (39%) boys had oligozoospermia and 4 (13%) had azoospermia, while 22 boys (71%) had low total motile sperm counts (TMSC) (<20 mil). Specifically, the eight boys in the TL3 group treated with DECOPDAC-21 consolidation had low sperm counts and low progressive motility after 2 years (i.e. median sperm count 1.4 mil/ml (IQR <0.1; 5.3), n = 7 (88%), low sperm concentration, low median progressive motility 16.5% (IQR 0.0; 51.2), respectively). Age-adjusted serum FSH levels were significantly raised and inhibin B levels (and inhibin B:FSH ratios) were decreased during chemotherapy in (post)pubertal boys, with subsequent normalization in 80% (for FSH) and 60% (for inhibin B) of boys after 2 years. Only 4 out of the 14 (post)pubertal boys (29%) with low sperm concentrations after 2 years had elevated FSH (>7.6 IU/l), while 7 (50%) had low inhibin B levels (<100 ng/l). In pre-pubertal boys, reproductive hormones were low overall and remained relatively stable during chemotherapy., Limitations, Reasons for Caution: The present analyses included sperm and laboratory measurements up to 2 years post-diagnosis. Long-term reproductive outcomes and potential recovery of spermatogenesis remain unknown, while recovery was reported up to 5- or even 10-year post-chemotherapy in previous studies.Boys who were pre-pubertal at diagnosis were still too young and/or physically not able to deliver semen after 2 years and we could not assess a potential difference in gonadotoxicity according to pubertal state at the time of treatment. Overall, the statistical power of the analyses on sperm concentration and quality after 2 years was limited., Wider Implications of the Findings: Results of the semen analyses conducted among the 31 boys who had provided a semen sample at 2 years post-treatment were generally poor. However, additional long-term and adequately powered data are crucial to assess the potential recovery and clinical impact on fertility. The participating boys will be invited to deliver a semen sample after 5 years. Until these data become available, benefits of intensified chemotherapy in cHL treatment to reduce radiotherapy and lower risk for development of secondary tumours should be carefully weighed against potentially increased risk of other late effects, such as diminished fertility due to the increased chemotherapy burden. Boys with newly diagnosed cHL should be encouraged to deliver sperm for cryopreservation whenever possible. However, patients and clinicians should also realize that the overall state of disease and inflammatory milieu of cHL can negatively affect sperm quality and thereby reduce chance of successful fertility preservation. Furthermore, the measurement of FSH and inhibin B appears to be of low value in predicting low sperm quality at two years from cHL treatment., Study Funding/competing Interest(s): This study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M.-K., D.K., W.H.W., D.H., MC, A.U., and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors declare no potential conflict of interest., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

G-protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by promoting guanine nucleotide exchange. Here, we investigate the coupling of G proteins with GPCRs and describe the events that ultimately lead to the ejection of GDP from its binding pocket in the Gα subunit, the rate-limiting step during G-protein activation. Using molecular dynamics simulations, we investigate the temporal progression of structural rearrangements of GDP-bound G s protein (G s ·GDP; hereafter G s GDP ) upon coupling to the β 2 -adrenergic receptor (β 2 AR) in atomic detail. The binding of G s GDP to the β 2 AR is followed by long-range allosteric effects that significantly reduce the energy needed for GDP release: the opening of α1-αF helices, the displacement of the αG helix and the opening of the α-helical domain. Signal propagation to the G s occurs through an extended receptor interface, including a lysine-rich motif at the intracellular end of a kinked transmembrane helix 6, which was confirmed by site-directed mutagenesis and functional assays. From this β 2 AR-G s GDP intermediate, G s undergoes an in-plane rotation along the receptor axis to approach the β 2 AR-G s empty state. The simulations shed light on how the structural elements at the receptor-G-protein interface may interact to transmit the signal over 30 Å to the nucleotide-binding site. Our analysis extends the current limited view of nucleotide-free snapshots to include additional states and structural features responsible for signaling and G-protein coupling specificity., Competing Interests: Competing interests G.S. is a co-founder of, and consultant for, Deep Apple Therapeutics. B.K.K. is a co-founder of, and consultant for, ConfometRx., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: Whereas (GCC)-repeats are overrepresented in genic regions, and mutation hotspots, they are largely unexplored with regard to their link with natural selection. Across numerous primate species and tissues, SMAD9 (SMAD Family Member 9) reaches highest level of expression in the human brain. This gene contains a (GCC)-repeat in the interval between + 1 and + 60 of the transcription start site, which is in the high-ranking (GCC)-repeats with respect to length., Methods: Here we sequenced this (GCC)-repeat in 396 Iranian individuals, consisting of late-onset neurocognitive disorder (NCD) (N = 181) and controls (N = 215)., Results: We detected two predominantly abundant alleles of 7 and 9 repeats, forming 96.2% of the allele pool. The (GCC)7/(GCC)9 ratio was in the reverse order in the NCD group versus controls (p = 0.005), resulting from excess of (GCC)7 in the NCD group (p = 0.003) and (GCC)9 in the controls (p = 0.01). Five genotypes, predominantly consisting of (GCC)7 and lacking (GCC)9 were detected in the NCD group only (p = 0.008). The patients harboring those genotypes received the diagnoses of Alzheimer's disease (AD) and vascular dementia (VD). Five genotypes consisting of (GCC)9 and lacking (GCC)7 were detected in the control group only (p = 0.002). The group-specific genotypes formed approximately 4% of the genotype pool in the human samples studied., Conclusion: We propose natural selection and a novel locus for late-onset AD and VD at the SMAD9 (GCC)-repeat in humans., (© 2024. Fondazione Società Italiana di Neurologia.)

Objective: The bejective was to determine health literacy (HL) and care aspects of those affected by Long-COVID., Method: 407 patients with Long-COVID and long-term neuropsychiatric symptoms were interviewed in the LIFE study center. In addition to descriptive analyses, regression models were calculated to examine the relationships between health literacy (HLS-EU-Q16) and various aspects of care (RehaQ-N1)., Results: The results show that 35.8% had problematic and 17.9% had inadequate HL. The majority of subjective needs were unmet and 47.7% of those affected were dissatisfied with the therapy they received., Discussion: Among those affected by Long-COVID, subjective HL is rather reduced. The healthcare system appears to be unprepared for these patients, which is reflected in unmet needs and low treatment satisfaction. This was even more pronounced among those exhibiting lower HL., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme. All rights reserved.)

Background: Self-help can play an important supplementary role in the treatment of people with severe mental illness; however, little is known about the utilization of the various approaches., Objective: This study describes the use of various self-help options by patients with severe mental illness and examines potential predictors., Material and Methods: As part of the observational cross-sectional study on patients with severe mental illness (IMPPETUS, N = 397), trained staff collected sociodemographic, illness-associated and treatment-associated data between March 2019 and September 2019. Binary logistic regression was used to analyze a possible association with the use of self-help., Results: The participants most frequently reported using self-help literature (n = 170; 45.5%) followed by self-help groups (n = 130; 33.2%), electronic mental health applications (n = 56; 15.5%) and self-management approaches (n = 54; 14.8%). Trialogue seminars (n = 36; 9.9%) were the least used by the participants. The utilization of the various approaches is influenced by sociodemographic and disease-related characteristics (age, education, marital status, migration background, age at onset of initial mental health problems, psychosocial functioning level) but not by factors associated with treatment., Conclusion: The potential of self-help is not being fully utilized in the sample investigated. The reported use of self-help approaches by the participants ranged between 10% and 46%. The various formats address specific target groups. More targeted information must be provided about the various options and the use of self-help in routine treatment must be actively fostered in order to increase the utilization of self-help., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Among the different micro- and nanostructures located on cuticular surfaces, grooming devices represent fundamental tools for insect survival. The present study describes the grooming microstructures of the damselfly Ischnura elegans (Odonata, Coenagrionidae) at the adult stage. These structures, situated on the foreleg tibiae, were observed using scanning electron microscopy, and the presence and distribution of resilin, an elastomeric protein that enhances cuticle flexibility, were analyzed using confocal laser scanning microscopy. Eye and antennal grooming behavior were analyzed to evaluate the particle removal efficiency in intact insects and in insects with ablated grooming devices. The grooming devices are constituted of long setae from which a concave cuticular lamina develops towards the medial side of the leg. Each seta shows a material gradient of resilin from its basal to the distal portion and from the seta to the cuticular lamina. The removal of the grooming devices induces a strong increase in the contaminated areas on the eyes after grooming. Further studies on insect grooming can provide valuable data on the functional morphology of insect micro- and nanostructures and can represent a starting point to develop advanced biomimetic cleaning tools., Competing Interests: All the authors declare that they have no conflict of interest., (Copyright © 2024, Piersanti et al.)

Bioimage analysis (BIA), a crucial discipline in biological research, overcomes the limitations of subjective analysis in microscopy through the creation and application of quantitative and reproducible methods. The establishment of dedicated BIA support within academic institutions is vital to improving research quality and efficiency and can significantly advance scientific discovery. However, a lack of training resources, limited career paths and insufficient recognition of the contributions made by bioimage analysts prevent the full realization of this potential. This Perspective - the result of the recent The Company of Biologists Workshop 'Effectively Communicating Bioimage Analysis', which aimed to summarize the global BIA landscape, categorize obstacles and offer possible solutions - proposes strategies to bring about a cultural shift towards recognizing the value of BIA by standardizing tools, improving training and encouraging formal credit for contributions. We also advocate for increased funding, standardized practices and enhanced collaboration, and we conclude with a call to action for all stakeholders to join efforts in advancing BIA., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

The enteric nervous system (ENS) consists of an extensive network of neurons and glial cells embedded within the wall of the gastrointestinal (GI) tract. Alterations in neuronal distribution and function are strongly associated with GI dysfunction. Current methods for assessing neuronal distribution suffer from undersampling, partly due to challenges associated with imaging and analyzing large tissue areas, and operator bias due to manual analysis. We present the Gut Analysis Toolbox (GAT), an image analysis tool designed for characterization of enteric neurons and their neurochemical coding using two-dimensional images of GI wholemount preparations. GAT is developed in Fiji, has a user-friendly interface, and offers rapid and accurate segmentation via custom deep learning (DL)-based cell segmentation models developed using StarDist, as well as a ganglia segmentation model in deepImageJ. We apply proximal neighbor-based spatial analysis to reveal differences in cellular distribution across gut regions using a public dataset. In summary, GAT provides an easy-to-use toolbox to streamline routine image analysis tasks in ENS research. GAT enhances throughput, allowing rapid unbiased analysis of larger tissue areas, multiple neuronal markers and numerous samples., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Halogenated closo -dodecaborates are very robust and versatile weakly coordinating anions for numerous applications. The introduction of additional substituents, e.g., pseudohalides, allows the tuning of their chemical and physical properties. In this report, the synthesis of the isocyanate-substituted closo -dodecaborates [B 12 X 11 (NCO)] 2- (X = H, F-I) was investigated. In an attempt to synthesize the undecahalogenated derivatives, a selective and halogen-dependent reaction yielding boron clusters carrying the functional groups amidinium (-NHCHNMe 2 ) and formamide (-NHC(O)H) was discovered. The halogenated anions were fully characterized by vibrational and NMR spectroscopy, mass spectrometry, and X-ray diffraction. Salts of the formamide-substituted anion [B 12 X 11 (NHC(O)H)] 2- are surprisingly thermally stable in the condensed phase. In contrast, collision-induced dissociation in the gas phase reveals that the isolated dianion [B 12 X 11 (NHC(O)H)] 2- in the gas phase preferentially loses water, while the protonated form, which was generated from decomposition of the tetraalkylammonium counterion [B 12 X 11 (NHC(O)H)H] - , tends to lose carbon monoxide. Possible reaction mechanisms are discussed.

Background: The predicted prevalence of people with dementia (PWD) in Germany has risen to 1.8 million since 2010. In the near future, we will see the approval of antibody therapies. The study aims to demonstrate the recent anti-dementia medication prescriptions and diagnosis prevalence., Methods: Data from 357 general practitioner (GP) and 71 specialist practices (SP) (1.1 Mio. patients) were analyzed to demonstrate the prevalence of dementia diagnoses and anti-dementia drug prescriptions between 2010 and 2021., Results: The diagnosis prevalence of PWD (Alzheimer's dementia) remained relatively constant in GP practices at 1.0-1.3% (0.19-0.21%). Among SP, the prevalence increased from 4.9% (2.8%) to 5.9% (3.6%). The anti-dementia prescription rate decreased in GP (from 0.14% to 0.10%) and increased in SP practices (from 2.1% to 2.4%)., Discussion: The diagnosis and prescription rate, especially in GP practices, remained below the prevalence forecasts and the expected prescriptions., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The red/green cyanobacteriochrome (CBCR) slr1393g3 exhibits a quantum yield of only 8 % for its forward photoconversion, significantly lower than other species from the same CBCR subfamily. The cause for this reduced photoconversion is not yet clear, although in the related NpR6012g4 dark-state structural heterogeneity of a paramount Trp residue has been proposed to cause the formation of nonproductive subpopulation. However, there is no such information on the equivalent residue in slr1393g3, W496. Here we use solid-state NMR to explore all possible sidechain rotamers of this Trp residue and their local interactions at the atomic level. The indole nitrogen (Nϵ1) is used as an NMR probe, achieved by site-specific 15 N-indole labeling of a quadruply Trp-deleted variant and trehalose vitrification technique. The data reveal a set of seven indole rotamers of W496 with four distinct environments for the Nϵ1-H group. Only a minority population of 20 % is found to retain the π-stacking and hydrogen-bonding interactions with the chromophore in the dark state that has been assigned to account for complete forward photoconversion. Our results demonstrate the direct role of W496 in modulating the forward quantum yield of slr1393g3 via rearrangement of its sidechain rotameric conformations., (© 2024 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)

Alpha-band activity is thought to be involved in orchestrating neural processing within and across brain regions relevant to various functions such as perception, cognition, and motor activity. Across different studies, attenuated alpha-band activity has been linked to increased neural excitability. Yet, there have been conflicting results concerning the consequences of alpha-band modulations for early sensory processing. We here examined whether movement-related alterations in visual alpha-band activity affected the early sensory processing of visual stimuli. For this purpose, in an EEG experiment, participants were engaged in a voluntary finger-tapping task while passively viewing flickering dots. We found extensive and expected movement-related amplitude modulations of motor alpha- and beta-band activity with event-related-desynchronization (ERD) before and during, and event-related-synchronization (ERS) after single voluntary finger taps. Crucially, while a visual alpha-band ERS accompanied the motor alpha-ERD before and during each finger tap, flicker-evoked Steady-State-Visually-Evoked-Potentials (SSVEPs), as a marker of early visual sensory gain, were not modulated in amplitude. As early sensory stimulus processing was unaffected by amplitude-modulated visual alpha-band activity, this argues against the idea that alpha-band activity represents a mechanism by which early sensory gain modulation is implemented. The distinct neural dynamics of visual alpha-band activity and early sensory processing may point to distinct and multiplexed neural selection processes in visual processing., (© 2024 The Author(s). Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Cannabidiol (CBD), a non-psychotropic main component of the Cannabis plant, has been approved as a drug in the European Union (EU) under the name "Epidyolex". However, its approval process as a food ingredient under the Novel Food Regulation was paused by the European Food Safety Authority (EFSA) due to a lack of safety data. Nevertheless, there is a growing, unregulated market in which CBD is advertised with various health claims and dosage instructions. Of particular concern is its toxic effect on the liver and possible reproductive toxicity in humans. Studies suitable for calculating the benchmark dose were identified from the available data. Animal studies yielded a benchmark dose lower confidence limit (BMDL) of 43 mg/kg bw/day, which translates into a safe human dose of approximately 15 mg/day. Only the Lowest-Observed-Adverse-Effect Level (LOAEL) of 4.3 mg/kg bw/day could be identified from the human data. This updated risk assessment confirmed a health-based guidance value (HBGV) of 10 mg/day based on human LOAEL. Despite the existing data gaps, preliminary regulation appears advisable because the current form of the gray CBD market is unacceptable from the standpoint of consumer safety and protection.

An organocatalytic, highly enantioselective [6 + 2]-cycloaddition of 2-methide-2 H -pyrroles with aryl acetaldehydes represents a novel and straightforward route toward densely substituted 2,3-dihydro-1 H -pyrrolizin-3-ols, which were generated with good yields and high enantio- and diastereoselectivity. This one-step process involves a BINOL-phosphoric acid catalyzed reaction of 1 H -pyrrole-2-carbinols with aryl acetaldehydes via the corresponding hydrogen-bonded, chiral 2-methide-2 H -pyrroles.

Part II of the S3 guideline report deals with the surgical treatment of hypopharyngeal carcinoma, neck dissection for oropharyngeal and hypopharyngeal carcinomas and adjuvant therapy options. Primary surgical therapy ± adjuvant radio- or radiochemotherapy and primary radio- or radiochemotherapy are established as primary therapies for local-regional hypopharyngeal carcinomas. Direct randomized comparisons of both basic therapeutic procedures were never conducted. Available registry data show a worse prognosis of hypopharyngeal carcinoma compared to oropharyngeal carcinomas in all locoregional tumor stages, regardless of the treatment method. For T1N0-T2N0 squamous cell carcinoma of the hypopharynx, there are no relevant differences in overall survival and locoregional relapse rate between primary surgical and primary non-surgical treatment. Primary surgical therapy ± adjuvant radiotherapy or radiochemotherapy and primary radiotherapy or radiochemotherapy are established as primary therapies for advanced but locoregionally limited hypopharyngeal carcinomas. Neck dissection is an integral part of the primary surgical treatment of oropharyngeal and hypopharyngeal cancer. There are only a few randomized studies on non-surgical organ preservation for advanced hypopharyngeal cancer as an alternative to pharyngolaryngectomy, but these have led to the recommendation of alternative concepts in the new guideline. The indication and implementation of postoperative adjuvant radiotherapy and radiochemotherapy for hypopharyngeal carcinoma do not differ from those for HPV/p16-negative and -positive oropharyngeal carcinoma., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Nicht‐Sponsor der Veranstaltung): nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Sponsor der Veranstaltung): nein Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

DNA double-strand break (DSB) repair by homologous recombination is initiated by DNA end resection, a process involving the controlled degradation of the 5'-terminated strands at DSB sites 1,2 . The breast cancer suppressor BRCA1-BARD1 not only promotes resection and homologous recombination, but it also protects DNA upon replication stress 1,3-9 . BRCA1-BARD1 counteracts the anti-resection and pro-non-homologous end-joining factor 53BP1, but whether it functions in resection directly has been unclear 10-16 . Using purified recombinant proteins, we show here that BRCA1-BARD1 directly promotes long-range DNA end resection pathways catalysed by the EXO1 or DNA2 nucleases. In the DNA2-dependent pathway, BRCA1-BARD1 stimulates DNA unwinding by the Werner or Bloom helicase. Together with MRE11-RAD50-NBS1 and phosphorylated CtIP, BRCA1-BARD1 forms the BRCA1-C complex 17,18 , which stimulates resection synergistically to an even greater extent. A mutation in phosphorylated CtIP (S327A), which disrupts its binding to the BRCT repeats of BRCA1 and hence the integrity of the BRCA1-C complex 19-21 , inhibits resection, showing that BRCA1-C is a functionally integrated ensemble. Whereas BRCA1-BARD1 stimulates resection in DSB repair, it paradoxically also protects replication forks from unscheduled degradation upon stress, which involves a homologous recombination-independent function of the recombinase RAD51 (refs. 4-6,8 ). We show that in the presence of RAD51, BRCA1-BARD1 instead inhibits DNA degradation. On the basis of our data, the presence and local concentration of RAD51 might determine the balance between the pronuclease and the DNA protection functions of BRCA1-BARD1 in various physiological contexts., (© 2024. The Author(s).)

Background: Population-based studies on the relationship between social isolation and obesity, which also include younger adults, are still lacking in Germany. The aim of this study is to investigate the prevalence of social isolation in people with and without obesity. In addition, socially isolated people with and without obesity are examined with regard to socio-demographic and socio-economic factors as well as with regard to depressive symptoms., Methods: This study was based on baseline data from the LIFE Adult Study (18-79 years) from the 2011-2014 study period. The sample comprised n = 8350 participants. In addition to socio-demographic characteristics and socio-economic status (SES), data on social isolation (LSNS-6), depression (ADS), and body mass index (BMI) were collected. Evaluations were carried out using inferential statistical analyses., Results: Overall, 13.1% of the total sample were affected by social isolation. Participants with obesity (20.4%) had a significantly (p < 0.001) higher prevalence compared to those without obesity (11.4%). A better social integration was significantly associated with younger age (p < 0.001), female sex (p < 0.001), being married (and cohabiting) (p < 0.001), higher socioeconomic status (p < 0.001), and lower depressive symptoms (p < 0.001)., Discussion: A higher BMI was not associated per se with poorer social integration. However, the present study showed that socially isolated people with obesity represent a special risk group for impaired mental health and had twice the prevalence of social isolation compared to those without obesity., (© 2024. The Author(s).)

Background: Loneliness is a widespread phenomenon, and it is associated with a variety of health problems and diseases. Unemployed individuals diagnosed with a mental illness (UMIs) are at a high risk of experiencing loneliness, with serious repercussions for their health and vocational rehabilitation. With this study we wanted to better understand the associations between sociodemographic variables, mental health, and loneliness in UMIs., Methods: We analyzed the data of 526 unemployed individuals that received means-tested benefits as well as at least one psychiatric diagnosis. Data were collected between September 2020 and September 2023. We conducted two robust regressions with loneliness (University of California, Los Angeles, Loneliness Scale, UCLA) as an outcome (N = 526). In the first regression, we used social network as a predictor (Lubben Social Network Scale, LSNS-6); in the second regression we included the additional predictors personal debt (yes/no), depression (Patient Health Questionnaire, PHQ-9), anxiety (Mini-Symptom-Checklist,MSCL), and somatization (MSCL) as well as age, gender, education, and living with a partner as control variables., Results: We found a significant negative association between social network and loneliness, and a significant positive association between a high level of education, depression, anxiety, and loneliness., Conclusions: Unemployed individuals diagnosed with a mental illness in our sample exhibited high levels of depression, anxiety, somatization, and loneliness. The associations between social network, mental health, and loneliness that we found emphasize the importance of psychological screening and/or diagnostics, and they highlight areas for prevention., (© 2024. The Author(s).)

Objective: Accurate psychodiagnostics is crucial for diagnosing and ensuring quality treatment for individuals with mental health disorders. However, there is limited understanding of psychodiagnostic practices within Psychosocial Centers (PSZ) when dealing with refugees, particularly in the presence of language and cultural barriers and resource constraints. This study aims to evaluate the current status and potential pathways for enhancing culturally sensitive diagnostics in this context., Methods: We conducted an online survey using a self-developed questionnaire with representatives from 32 PSZ to examine psychodiagnostic practices, barriers, and perceived development potentials, and analyzed the data descriptively., Results: Most centers prefer individual case assessments over standardized diagnostics. Key barriers to using standardized questionnaires and interviews include communication difficulties (unfamiliarity with question formats, reading and writing difficulties) and resource limitations (time, translation). When conducting diagnostics, time constraints and prioritizing complex cases are the primary challenges. Additional assessments are needed for several disorders and languages. Employees are interested in receiving training in the field of culturally sensitive diagnostics., Discussion: Diagnostic practice in the PSZs is characterized by numerous challenges that differ from the challenges in standard care. In order to ensure appropriate standardized diagnostics and care for mentally distressed people with a refugee or migrant background, further expansion of the linguistic and cultural adaptation of established diagnostic instruments is essential., Conclusion: In the care of psychologically distressed refugees, culturally sensitive standardized diagnostics offer critical benefits for both practitioners and affected individuals. Existing resources are being referred to., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The aim of this study was to describe how the therapy of anorexia nervosa (AN) and food refusal have been discussed in leading textbooks used in German-speaking academic psychiatry over the past 200 years. For this purpose, 18 textbooks of important school psychiatrists were selected. These were analyzed in a structured way to determine the content of the subject taught at universities in German-speaking countries at a given period. We found that AN was not taught as a distinct disorder until the end of the 20th century, although great attention had been paid to food refusal as a symptom and manifold therapeutic concepts had been developed much earlier. Whereas at the beginning of the 19th century forced feeding using feeding tubes was established, in the following years pharmacotherapies and special diets were developed. It is noteworthy that since the beginnings of academic psychiatry, some early forms of psychotherapy have been developed; for instance, special kinds of behavior were recommended when dealing with the patient, as the therapist was supposed to serve as a role model to encourage patients to eat. Treatment of food refusal by means of structured psychotherapeutic approaches were not established before AN was generally accepted as a distinct disease entity. The understanding of etiological factors that might lead to AN as well as potential psychotherapeutic interventions have changed fundamentally over the past decades., Competing Interests: Alle Autor*innen geben keinen Interessenkonflikt zum Inhalt dieses Beitrags an., (Thieme. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Zebrafish ( Danio rerio ) is an important animal model for a wide range of neurodegenerative diseases. However, obtaining the cellular resolution that is essential for studying the zebrafish brain remains challenging as it requires high spatial resolution and signal-to-noise ratios (SNR). In the current study, we present the first MRI results of the zebrafish brain at the state-of-the-art magnetic field strength of 28.2 T. The performance of MRI at 28.2 T was compared to 17.6 T. A 20% improvement in SNR was observed at 28.2 T as compared to 17.6 T. Excellent contrast, resolution, and SNR allowed the identification of several brain structures. The normative T 1 and T 2 relaxation values were established over different zebrafish brain structures at 28.2 T. To zoom into the white matter structures, we applied diffusion tensor imaging (DTI) and obtained axial, radial, and mean diffusivity, as well as fractional anisotropy, at a very high spatial resolution. Visualisation of white matter structures was achieved by short-track track-density imaging by applying the constrained spherical deconvolution method (stTDI CSD). For the first time, an algorithm for stTDI with multi-shell multi-tissue (msmt) CSD was tested on zebrafish brain data. A significant reduction in false-positive tracks from grey matter signals was observed compared to stTDI with single-shell single-tissue (ssst) CSD. This allowed the non-invasive identification of white matter structures at high resolution and contrast. Our results show that ultra-high field DTI and tractography provide reproducible and quantitative maps of fibre organisation from tiny zebrafish brains, which can be implemented in the future for a mechanistic understanding of disease-related microstructural changes in zebrafish models of various brain diseases.

Functionalization of surface-grown coordination polymer layers by ion soft-landing of highly reactive molecular fragment ions is demonstrated. The ions form covalent bonds to terminal functional groups of the polymer at the vacuum interface, opening new perspectives for controlled bond formation using reactive ions.

This study presents a new risk assessment of pulegone, a substance classified as possibly carcinogenic to humans (Group 2B) by the WHO International Agency for Research on Cancer (IARC). The analysis used data from a two-year carcinogenicity studies in rats and mice conducted by the National Toxicology Program (NTP) in 2011. Because of the absence of a no-observed adverse effect level (NOAEL) in these studies, the benchmark dose (BMD) approach was employed as an alternative risk assessment method. The lowest BMD lower confidence level (BMDL) of 4.8 mg/kg b.w./day among the eight endpoints served as the point of departure for calculating an acceptable daily intake (ADI) of 48 μg/kg b.w./day. This new ADI is significantly lower than the previously established tolerable daily intake of 0.1 mg/kg b.w./day set in 1997. The analysis also considered various genotoxicity studies, which indicate that pulegone's effects follow a nongenotoxic, thresholded mechanism. The estimated intake levels of pulegone in the European Union and USA were below the newly calculated ADI, suggesting a low health risk based on current consumption patterns.

This study aimed to develop a graph neural network (GNN) for automated three-dimensional (3D) magnetic resonance imaging (MRI) visualization and Pfirrmann grading of intervertebral discs (IVDs), and benchmark it against manual classifications. Lumbar IVD MRI data from 300 patients were retrospectively analyzed. Two clinicians assessed the manual segmentation and grading for inter-rater reliability using Cohen's kappa. The IVDs were then processed and classified using an automated convolutional neural network (CNN)-GNN pipeline, and their performance was evaluated using F1 scores. Manual Pfirrmann grading exhibited moderate agreement (κ = 0.455-0.565) among the clinicians, with higher exact match frequencies at lower lumbar levels. Single-grade discrepancies were prevalent except at L5/S1. Automated segmentation of IVDs using a pretrained U-Net model achieved an F1 score of 0.85, with a precision and recall of 0.83 and 0.88, respectively. Following 3D reconstruction of the automatically segmented IVD into a 3D point-cloud representation of the target intervertebral disc, the GNN model demonstrated moderate performance in Pfirrmann classification. The highest precision (0.81) and F1 score (0.71) were observed at L2/3, whereas the overall metrics indicated moderate performance (precision: 0.46, recall: 0.47, and F1 score: 0.46), with variability across spinal levels. The integration of CNN and GNN offers a new perspective for automating IVD analysis in MRI. Although the current performance highlights the need for further refinement, the moderate accuracy of the model, combined with its 3D visualization capabilities, establishes a promising foundation for more advanced grading systems., (© 2024. The Author(s).)

In an effort to expand the domain of mathematical chemistry and inspire research beyond the realms of graph theory and quantum chemistry, we explore five mathematical chemistry spaces and their interconnectedness. These spaces comprise the chemical space, which encompasses substances and reactions; the space of reaction conditions, spanning the physical and chemical aspects involved in chemical reactions; the space of reaction grammars, which encapsulates the rules for creating and breaking chemical bonds; the space of substance properties, covering all documented measurements regarding substances; and the space of substance representations, composed of the various ontologies for characterising substances., (© 2024. The Author(s).)

Nudibranchs, with their mesmerizing diversity and ecological significance, play crucial roles in marine ecosystems. Central to their feeding prowess is the radula, a chitinous structure with diverse morphologies adapted to prey preferences and feeding strategies. This study focuses on elucidating wear coping mechanisms in radular teeth of carnivorous molluscs, employing Dendronotus lacteus (Dendronotidae) and Flabellina affinis (Flabellinidae) as model species. Both species forage on hydrozoans. Through scanning electron microscopy, confocal laser scanning microscopy, nanoindentation, and energy-dispersive X-ray spectroscopy, the biomechanical and compositional properties of their teeth were analyzed. Notably, tooth coatings, composed of calcium (Ca) or silicon (Si) and high hardness and stiffness compared to the internal tooth structure, with varying mineral contents across tooth regions and ontogenetic zones, were found. The presence of the hard and stiff tooth coatings highlight their role in enhancing wear resistance. The heterogeneities in the autofluorescence patterns related to the distribution of Ca and Si of the coatings. Overall, this study provides into the biomechanical adaptations of nudibranch radular teeth, shedding light on the intricate interplay between tooth structure, elemental composition, and ecological function in marine molluscs., (© 2024 The Author(s). Journal of Morphology published by Wiley Periodicals LLC.)

Aim: This article is part of the EKB-study which explores lived crisis and treatment experiences of mental health professionals in Berlin and Brandenburg. It addresses the disclosure of mental health workers' lived experiences in their workplace., Method: An online survey was conducted among 182 mental health professionals, containing questions on disclosure of lived experiences. Data were analyzed descriptively and analytically., Results: Participants reported disclosure mainly to supervisors and affiliated colleagues. Experiences were mostly positive, with severe negative exceptions. Central motives against disclosure were fear of vulnerability, fear of compromising professional identity, and shame., Conclusions: Disclosure of lived crisis experiences is not always the proper strategy for mental health professionals. Disclosure may be a means of reducing public and internalized stigma., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Early diagnosis of neosporosis in dogs is challenging., Objectives: To evaluate the feasibility of a compound multimodal testing approach for diagnosing in dogs neuromuscular and combined forms of neosporosis., Animals: A total of 16 dogs diagnosed with solely neuromuscular neosporosis or with a combination of neuromuscular and central nervous system neosporosis., Methods: Retrospective review of clinical signs, laboratory findings, treatment, and outcome with focus on the diagnostic utility of different tests. Development of a chromogenic in situ hybridization (ISH) assay for the identification of Neospora caninum in paraffin-embedded muscle samples., Results: 13/16 dogs had only neuromuscular signs of neosporosis, 3/16 had disease signs with concomitant central nervous system (CNS) involvement. Serology was performed in 15/16, with 10/15 showing titers >1 : 160 at admission. PCR on muscle samples detected N. caninum DNA in 11/16. Immunohistochemistry (IHC) detected N. caninum in 9/16 and ISH in 9/16. Histopathology revealed inflammatory myopathy in 10/16, necrotizing myopathy in 5/16, borderline changes in 1/16 and tachyzoites in 9/16. In 4 cases, N. caninum infection was confirmed with all 5 diagnostic methods, 3 cases with 4, 2 with 3, 6 with 2, and 1 animal with 1., Conclusions and Clinical Importance: Diagnosis of N. caninum infection should rely on a multimodal diagnostic approach and negativity of 1 single test should not allow for exclusion. Serology in combination with direct parasite identification via histopathology, DNA via PCR, or both modalities, appears a reliable diagnostic approach., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Ionic gating of oxide thin films has emerged as a novel way of manipulating the properties of thin films. Most studies are carried out on single devices with a three-terminal configuration, but, by exploring the electrokinetics during the ionic gating, such a configuration with initially insulating films leads to a highly non-uniform gating response of individual devices within large arrays of the devices. It is shown that such an issue can be circumvented by the formation of a uniform charge potential by the use of a thin conducting underlayer. This synchronized local ionic gating allows for the simultaneous manipulation of the electrical, magnetic, and/or optical properties of large arrays of devices. Designer metasurfaces formed in this way from SrCoO 2.5 thin films display an anomalous optical reflection of light that relies on the uniform and coherent response of all the devices. Beyond oxides, almost any material whose properties can be controlled by the addition or removal of ions via gating can form novel metasurfaces using this technique. These findings provide insights into the electrokinetics of ionic gating and a wide range of applications using synchronized local ionic gating., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Ethical Considerations of Including Minors in Clinical Trials Using the Example of the Indicated Prevention of Psychotic Disorders Abstract: As a vulnerable group, minors require special protection in studies. For this reason, researchers are often reluctant to initiate studies, and ethics committees are reluctant to authorize such studies. This often excludes minors from participating in clinical studies. This exclusion can lead to researchers and clinicians receiving only incomplete data or having to rely on adult-based findings in the treatment of minors. Using the example of the study "Computer-Assisted Risk Evaluation in the Early Detection of Psychotic Disorders" (CARE), which was conducted as an 'other clinical investigation' according to the Medical Device Regulation, we present a line of argumentation for the inclusion of minors which weighs the ethical principles of nonmaleficence (especially regarding possible stigmatization), beneficence, autonomy, and fairness. We show the necessity of including minors based on the development-specific differences in diagnostics and early intervention. Further, we present specific protective measures. This argumentation can also be transferred to other disorders with the onset in childhood and adolescence and thus help to avoid excluding minors from appropriate evidence-based care because of insufficient studies.

Background: Although people receiving means-tested benefits are regularly taken care of at the job center, little is known about their mental health situation and mental health care., Objective: The aim of the study was to describe the diagnostic spectrum and the functional status as well as the mental health care utilization of individuals with mental illnesses who are receiving means-tested benefits., Methods: Mentally ill people with means-tested benefits were recruited at the job center as part of the "Leipzig Individual Placement and Support for Mentally Ill People" (LIPSY) project, where they were initially diagnosed according to ICD-10 and included in the project if they had a mental disorder. Mental healthcare utilization was recorded. In the present study, data from n = 583 consecutively included persons were analyzed descriptively and by multivariate statistics., Results: Of the study participants 60.7% (n = 583; 51.5% female; average age 36 years; unemployed for an average of 4.8 years) suffered from affective disorders, followed by neurotic, stress and somatoform disorders (42.5%). With a mean global assessment of functioning (GAF) value of 49.4 (SD 7.7), there was on average a serious impairment. Nearly half of the subjects (48.5%) had never received psychotherapeutic, psychiatric or neurological treatment in the 6 months prior to inclusion in the project., Discussion: It could be shown that there is a broad spectrum of mental disorders with substantial functional impairment. The data suggest that this group is significantly undertreated and difficult to reach., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Lynch syndrome (LS) is the most frequent hereditary tumor syndrome and is associated with an increased risk of colorectal cancer (CRC). While gene-specific and age-specific differences are considered in patient surveillance, gender-specific risks in the development of CRC have been reported in many studies but are not consistently documented., Objective: This systematic review aims to investigate gender-specific differences in CRC development among LS patients., Material and Methods: A systematic literature search following PRISMA 2020 guidelines was conducted in the PubMed, Ovid, The Cochrane Library and Web of Science databases. A total of 688 studies were screened, and 41 met the inclusion criteria., Results: Men have a higher risk of CRC and develop CRC earlier compared to women., Conclusion: These findings indicate gender-specific differences in the risk of CRC among LS patients, although they do not currently justify separate surveillance strategies., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Centipedes are terrestrial and predatory arthropods that possess an evolutionary transformed pair of appendages used for venom injection-the forcipules. Many arthropods incorporate reinforcing elements into the cuticle of their piercing or biting structures to enhance hardness, elasticity or resistance to wear and structural failure. Given their frequent exposure to high mechanical stress, we hypothesise that the cuticle of the centipede forcipule might be mechanically reinforced. With a combination of imaging, analytical techniques and mechanical testing, we explore the centipede forcipule in detail to shed light on its morphology and performance. Additionally, we compare these data to characteristics of the locomotory leg to infer evolutionary processes., Results: We examined sclerotization patterns using confocal laser-scanning microscopy based on autofluorescence properties of the cuticle (forcipule and leg) and elemental composition by energy-dispersive X-ray spectroscopy in representative species from all five centipede lineages. These experiments revealed gradually increasing sclerotization towards the forcipular tarsungulum and a stronger sclerotization of joints in taxa with condensed podomeres. Depending on the species, calcium, zinc or chlorine are present with a higher concentration towards the distal tarsungulum. Interestingly, these characteristics are more or less mirrored in the locomotory leg's pretarsal claw in Epimorpha. To understand how incorporated elements affect mechanical properties, we tested resistance to structural failure, hardness (H) and Young's modulus (E) in two representative species, one with high zinc and one with high calcium content. Both species, however, exhibit similar properties and no differences in mechanical stress the forcipule can withstand., Conclusions: Our study reveals similarities in the material composition and properties of the forcipules in centipedes. The forcipules transformed from an elongated leg-like appearance into rigid piercing structures. Our data supports their serial homology to the locomotory leg and that the forcipule's tarsungulum is a fusion of tarsus and pretarsal claw. Calcium or zinc incorporation leads to comparable mechanical properties like in piercing structures of chelicerates and insects, but the elemental incorporation does not increase H and E in centipedes, suggesting that centipedes followed their own pathways in the evolutionary transformation of piercing tools., (© 2024. The Author(s).)