Search

Introduction Cognitive impairment in Bipolar Disorder (BD) is frequent and is associated with reduced function in several areas. Close to half of the patients with BD have persistent cognitive dysfunction. The causes of cognitive impairments and factors associated with normal cognitive function are not clearly described. Some preliminary evidence links sleep disturbances and cognition impairment in BD. A limited number of studies have investigated the link between sleep and cognitive function in BD using objective measures. Objectives We aim to investigate associations between sleep and objective and subjective cognitive function in patients with BD in full or partial remission. Methods This is a cross-sectional study. The participants will be 90 adults meeting criteria for DSM 5 BD type 1 or type 2 in full or partial remission. Participants are recruited from psychoeducational groups for BD and from a specialist outpatient clinic. Diagnoses are set with SCID-5 and are confirmed in a consensus meeting with at least two psychiatrists and/or specialists in psychology. Symptoms of depression and mania are measured with Montgomery Asberg depression rating scale (MADRS) and Young Mania Rating Scale (YMRS). Sleep is measured subjectively with Insomnia Severity Index (ISI) and objectively with actigraphs which participants wear on their non-dominant hand for ten days. Subjective cognition is measured with Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA). Participants undergo neurocognitive testing with a self-administered validated web-based neuropsychological test platform. The testing is carried out in the participant’s home on their smart phones. The tests include measures of learning, storing, recalling, and recognizing visual and verbal information, working memory and reaction time. Normal cognitive function is defined as scores within or above mean on all cognitive subtests. The test-platform has been validated. We will use descriptive statistics to examine distribution of demographic characteristics. We will test for correlations between sleep factors and subjective and objective measures of cognitive function. Ethics The Regional Committees for Medical and Health research ethics approved the study. Results Results will be presented at the conference. So far, 74 out of 90 participants have been included. Conclusions We anticipate that normal sleep may be associated with good cognitive functioning. The findings of this study could offer supplementary insights into BD heterogeneity and potential treatment targets. Abbreviations: SCID-5, Structured Clinical Interview for DSM-5 Disclosure of Interest None Declared

This study explores the synchronization of multimodal physiological data streams, in particular, the integration of electroencephalography (EEG) with a virtual reality (VR) headset featuring eye-tracking capabilities. A potential use case for the synchronized data streams is demonstrated by implementing a hybrid steady-state visually evoked potential (SSVEP) based brain-computer interface (BCI) speller within a fully immersive VR environment. The hardware latency analysis reveals an average offset of 36 ms between EEG and eye-tracking data streams and a mean jitter of 5.76 ms. The study further presents a proof of concept brain-computer interface (BCI) speller in VR, showcasing its potential for real-world applications. The findings highlight the feasibility of combining commercial EEG and VR technologies for neuroscientific research and open new avenues for studying brain activity in ecologically valid VR environments. Future research could focus on refining the synchronization methods and exploring applications in various contexts, such as learning and social interactions.

Providing targeted experiences for first-year students both inside and outside the classroom is essential for building connections and creating a foundation for skill development necessary for academic success. Many first-year programs include a standalone course for incoming students or specific content weaved into existing course offerings. Information literacy skill-building holds an important place in these efforts; therefore, instruction librarians are provided additional opportunities to collaborate with faculty and reach students. Depending upon the size of the institution, however, the sheer number of first-year courses combined with shrinking library staff pose challenges. This Innovative Practices article is one library’s experience with building, executing, and assessing an information literacy program specific to the needs of first-year students in response to these challenges. Offering an array of library resources, collaborating on ideas for instruction delivery, and crafting a more intentional approach to assigning classes are solutions that may be adapted to address scalability and sustainability concerns.

Non-IgA vasculitis is a rare disease that belongs to the group of small-vessel vasculitides. Due to nomenclature and classification changes introduced in 2018, there are few published data under this name. The aim of this study is to characterize non-IgA vasculitis as an independent vasculitis entity in terms of demographic, clinical, and treatment-related features. A retrospective data analysis of patients with biopsy-confirmed non-IgA vasculitis treated at the Department of Dermatology at the University Medical Center Hamburg-Eppendorf between January 1, 2018, and December 31, 2022, was performed. A total of 28 patients with non-IgA vasculitis were included; 53.6% (15/28) were women and 42.9% (12/28) were older than 71 years. Previous infection as a possible triggering factor was found in 42.6% (12/28) of the cases. Palpable purpura was the most common skin finding (78.6%, 22/28) and 28.6% patients (8/28) had skin lesions above the waist. On direct immunofluorescence, C3 (89.3%, 25/28) was the most frequent deposition, followed by fibrinogen (71.4%, 20/28) and IgM (53.6%, 15/28). Hospitalization was required in 85.7% (24/28), with a mean hospital stay of 9.4 ± 4.1 days. No fatal courses were reported. This study is the first characterization of non-IgA vasculitis based on patient cases from Germany and contributes to a better understanding of non-IgA vasculitis as an independent entity. Non-IgA vasculitis primarily affects older patients of both sexes, with most cases having an identifiable trigger. Our results indicate that cutaneous manifestations often extend beyond the lower legs. Treatment is usually required in the inpatient setting and requires a longer stay than other dermatological conditions. With proper treatment, the disease is not expected to be fatal., (© 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Background: Interferon-alpha is an important therapeutic option for the treatment of the cutaneous T-cell lymphomas (CTCL). Since the approved recombinant interferon-α-2a (IFN-α2a) has no longer been produced since January 2020, pegylated interferon-α2a (pegIFN-α2a) can be used as an alternative treatment, even though it is not approved for the treatment of CTCL. The aim of this multicentre study was to generate comprehensive data on the efficacy and tolerability of pegIFN-α2a in the treatment of CTCL., Patients and Methods: A multicenter retrospective study was conducted with 70 patients with CTCL from twelve German skin centers., Results: In total, 70 patients were included in the study, with 57.2% male and a mean age of 58.8 ± 14.9 years. Mycosis fungoides was present in 71.4% of cases and Sézary Syndrome in 28.6%. An overall response rate of 55.2% was observed with pegIFNα-2a therapy. In 50% of cases, therapy was discontinued after 63.6 ± 33.5 weeks. The most common reason for discontinuation was adverse events, which occurred in 68.6% of cases and which were classified as severe in 29.2%. Blood count changes, fatigue and liver toxicity occurred most frequently., Conclusions: Our analysis provides comprehensive data on the efficacy and tolerability of pegIFNα-2a therapy in patients with CTCL. In terms of response rates and side effect profile, pegIFNα-2a appears to be comparable to IFN-α2a therapy., (© 2024 The Author(s). Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Background: Adjuvant treatment of stage II-IV melanoma with PD-1-based immune checkpoint inhibitors (ICI) has improved relapse-free survival (RFS) and has therefore become a standard-of-care treatment option. Approximately 25%-30% of patients still recur within 1 year. Predictive biomarkers reflecting real-world data are desired. The predictive relevance of tumour tissue PD-L1 expression in the adjuvant setting remains inconclusive., Objectives: This retrospective, observational study was conducted to evaluate the value of PD-L1 expression scores in different tumour tissue locations in predicting response towards adjuvant immunotherapeutic treatment., Methods: Tumour tissue taken prior to anti-PD-1 adjuvant ICI in 243 stage II-IV melanoma patients was collected at University Skin Cancer Center Hamburg. PD-L1 expression was evaluated on immune cells (ICS), tumour cells (TPS) and combined (CPS). Scores were determined by independent pathological physician quantification and correlated with therapy outcome at different cut-off (CO) levels (relapse-free survival, RFS) for different tumour tissue locations (primary tumour, metastases)., Results: A total of 104 patients were eligible for analysis. Positivity of ICS, TPS and CPS showed no predictive RFS outcome association at different CO levels when analysed irrespective of tissue origin. In primary tumours, ICS at CO 1% showed a significantly improved RFS upon positivity (HR 0.22). In contrast, positivity to TPS (CO 1%) correlated significantly and independently with improved RFS when evaluated in metastatic tumour tissue specimens (HR 0.37)., Conclusions: PD-L1 tumour tissue expression may serve as a predictive biomarker for adjuvant ICI treatment response stratification in melanoma, but caution should be spent on the origin of tumour tissue analysed. The cell-type relevant for the predictive value of PD-L1 expression is tissue-specific with immune cells being important in primary tumours while tumour cells are key in metastases. The present results should be validated in a multicentre cohort., (© 2024 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Neurofilament light chain (NfL) is known for indicating adult brain injury, but the role of NfL in extremely preterm infants is less studied. This study examines the relationship between NfL and neurovascular morbidities in these infants., Methods: A secondary analysis of the Mega Donna Mega trial was conducted on preterm infants <28 weeks gestational age (GA). The study measured NfL levels and proteomic profiles related to the blood-brain barrier in serum from birth to term-equivalent age, investigating the association of NfL with GA, retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), and blood-brain barrier proteins., Results: Higher NfL levels were seen in the first month in infants with severe IVH and for those born <25 weeks GA (independent of ROP or IVH). Additionally, infants born at 25-27 weeks GA with high NfL were at increased risk of developing severe ROP (independent of IVH). NfL was significantly associated with the proteins CDH5, ITGB1, and JAM-A during the first month., Conclusion: NfL surges after birth in extremely preterm infants, particularly in those with severe IVH and ROP, and in the most immature infants regardless of IVH or ROP severity. These findings suggest NfL as a potential predictor of neonatal morbidities, warranting further validation studies., Impact Statement: This study shows that higher NfL levels are related to neurovascular morbidities in extremely preterm infants. The degree of immaturity seems important as infants born <25 weeks gestational age exhibited high postnatal serum NfL levels irrespective of neurovascular morbidities. Our findings suggest a potential link between NfL and neurovascular morbidities possibly affected by a more permeable blood-brain barrier., (© 2024. The Author(s).)

Semiconductor spin qubits represent a promising platform for future large-scale quantum computers owing to their excellent qubit performance, as well as the ability to leverage the mature semiconductor manufacturing industry for scaling up. Individual qubit control, however, commonly relies on spectral selectivity, where individual microwave signals of distinct frequencies are used to address each qubit. As quantum processors scale up, this approach will suffer from frequency crowding, control signal interference and unfeasible bandwidth requirements. Here, we propose a strategy based on arrays of degenerate spins coherently dressed by a global control field and individually addressed by local electrodes. We demonstrate simultaneous on-resonance driving of two degenerate qubits using a global field while retaining addressability for qubits with equal Larmor frequencies. Furthermore, we implement SWAP oscillations during on-resonance driving, constituting the demonstration of driven two-qubit gates. Significantly, our findings highlight how dressing can overcome the fragility of entangling gates between superposition states and increase their noise robustness. These results constitute a paradigm shift in qubit control in order to overcome frequency crowding in large-scale quantum computing., (© 2024. The Author(s).)

Background: Oral finasteride and topical minoxidil are the current standard of care for male androgenetic alopecia and a combination of the two treatments can be considered for greater efficacy. Clinical trials of topical finasteride have also yielded promising results, but routine care data are lacking., Aims: To examine patient-reported outcomes of men with androgenetic alopecia who received topical finasteride admixed with minoxidil compared to the current standard of care (oral finasteride)., Methods: Retrospective, cross-sectional study with data from a German direct-to-consumer teledermatology platform between December 2021 and January 2023. Patient-reported outcomes were collected through voluntary follow-up questionnaires provided after 6 weeks on topical finasteride/minoxidil or oral finasteride treatment., Results: A total of 1545 patients who received topical finasteride/minoxidil treatment were included; 238 (15.4%) participated in the follow-up questionnaire. At week six, 62.2% (148/238) reported positive changes in their hair appearance, and 44.1% (105/238) reported an improvement of self-esteem. Treatment-related adverse events were reported in 11.8% (28/238). Full treatment adherence was observed in 74.4% (177/238). Comparing the topical treatment group to those receiving oral finasteride, lower treatment adherence was reported, along with higher rates of local adverse events; no difference was found in the incidence of sexual adverse events., Conclusion: Based on patient-reported outcomes, topical finasteride/minoxidil seems to be effective and well tolerated, but not superior to oral finasteride. Lower treatment adherence for topical usage must be considered when considering treatment options. Additional real-world data are needed to further evaluate the efficacy and safety of topical finasteride/minoxidil., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Congenital myasthenic syndromes (CMS) are a group of genetic disorders characterized by impaired neuromuscular transmission. CMS typically present at a young age with fatigable muscle weakness, often with an abnormal response after repetitive nerve stimulation (RNS). Pharmacologic treatment can improve symptoms, depending on the underlying defect. Prevalence is likely underestimated. This study reports on patients with CMS followed in Belgium in 2022., Methods: Data were gathered retrospectively from the medical charts. Only likely pathogenic and pathogenic variants were included in the analysis., Results: We identified 37 patients, resulting in an estimated prevalence of 3.19 per 1,000,000. The patients harbored pathogenic variants in CHRNE, RAPSN, DOK7, PREPL, CHRNB1, CHRNG, COLQ, MUSK, CHRND, GFPT1, and GMPPB. CHRNE was the most commonly affected gene. Most patients showed disease onset at birth, during infancy, or during childhood. Symptom onset was at adult age in seven patients, caused by variants in CHRNE, DOK7, MUSK, CHRND, and GMPPB. Severity and distribution of weakness varied, as did the presence of respiratory involvement, feeding problems, and extraneuromuscular manifestations. RNS was performed in 23 patients of whom 18 demonstrated a pathologic decrement. Most treatment responses were predictable based on the genotype., Conclusions: This is the first pooled characterization of patients with CMS in Belgium. We broaden the phenotypical spectrum of pathogenic variants in CHRNE with adult-onset CMS. Systematically documenting larger cohorts of patients with CMS can aid in better clinical characterization and earlier recognition of this rare disease. We emphasize the importance of establishing a molecular genetic diagnosis to tailor treatment choices., Competing Interests: Declaration of competing interest There has been no commercial involvement in the study design or manuscript preparation, and none of the authors report any other conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Skin diseases in patients with skin of colour (Fitzpatrick skin types IV to VI) are underrepresented in dermatology training, which may lead to lower quality of care for these patients. To address this underrepresentation in medical education, a newly developed seminar on skin type diversity using an interactive teaching method was implemented in an undergraduate medical curriculum. This study examined the effects of a seminar on the self-assessed competence of medical students in managing skin conditions in patients with skin of colour., Methods: A questionnaire survey was conducted among fourth-year undergraduate medical students at the University of Hamburg (Germany) between October 2023 and February 2024. Students' self-assessed competence was compared before and after the obligatory seminar (pre- and post-design)., Results: In total, 158 students participated in the survey. After the seminar, knowledge of the presentation of skin diseases in patients with skin of colour and the associated psychological burden, differences in the incidence of skin diseases in different skin types, and the ability to diagnose skin diseases in darker skin types increased. Most participants stated that they wanted to attend more courses on this topic., Discussion: Appropriate courses for medical students can improve their competence in managing different skin diseases in patients with skin of colour. In the future, more attention should be paid to teaching the diversity of skin types in dermatology education., (© 2024. The Author(s).)

Mogamulizumab, a monoclonal antibody directed against CC chemokine receptor 4, is approved as a second-line treatment of mycosis fungoides and Sézary syndrome. One of the most common side effects is mogamulizumab-associated rash (MAR), which can present in a variety of clinical and histological types. Clinically, it can be difficult to differentiate between MAR and progression of the underlying disease, so histological examination is crucial for clinicopathological correlation. Current data analyses suggest that MAR is more common in patients with Sézary syndrome and is associated with a significantly better response to treatment, making the distinction from disease progression particularly important. The management of MAR depends on its severity, and therapy may need to be paused. This article presents three cases from our clinic and reviews the current literature on MAR. It emphasizes the importance of understanding MAR in the management of patients with cutaneous lymphomas., (© 2024 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Background: The treatment of melanoma has been revolutionized by the use of immune checkpoint inhibition (ICI), but many patients do not benefit. Furthermore, immune-related adverse events may occur during therapy. A predictive biomarker is needed to reliably identify patients benefitting. In lung, renal cell and bladder cancer early C-reactive protein (CRP) kinetics were shown to be a predictive biomarker for ICI., Objective: Here, we investigate early CRP kinetics as predictive biomarker for ICI in melanoma patients., Methods: Two independent prospectively collected cohorts were analysed: Cohort 1 (n = 87) with advanced and Cohort 2 (n = 99) with completely resected melanoma. Patients were stratified by in the dynamics of CRP after ICI initiation: A doubling of baseline CRP within 30 days followed by at least a 30% drop within 3 months was classified as a CRP flare. If no doubling of CRP was reported, but a 30% drop within 3 months, patients were classified as CRP responders and all others as CRP non-responders. Analysed factors included clinical characteristics like S100B and LDH. Median follow-up was 1.5 and 1.7 years for Cohorts 1 and 2., Results: In Cohort 1 CRP flare (n = 12), CRP responders (n = 43) and CRP non-responders (n = 32) with a progression-free survival (PFS) of 0.7, 0.6 and 0.2 years (p = 0.017) and an overall survival (OS) of 2.2, 1.5 and 1.0 years (p = 0.014), respectively. Multivariable Cox analysis showed an independent risk reduction of progression for CRP responders by 62% compared to CRP non-responders (p = 0.001). In Cohort 2 CRP flare (n = 13), CRP responders (n = 70) and CRP non-responders (n = 16) the log-rank analysis showed a significant difference between OS and recurrence-free survival (RFS) curves (p = 0.046 and p = 0.049)., Conclusion: Early CRP kinetics could indicate a response to ICI with improved OS and RFS/PFS. CRP flare and CRP response indicating significantly improved outcomes compared to CRP non-responders., (© 2024 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Objective: A low expression of club cell secretory protein (CC16) and high levels of proinflammatory cytokines at preterm birth are associated with airway inflammation and more severe neonatal lung disease. The present study aimed to investigate if low levels of CC16, proinflammatory cytokines and vascular endothelial growth factors (VEGF) in tracheal aspirate early after birth were associated with lung function impairment at school age., Patients and Methods: Participants were 20 children, born very preterm (median gestational age 25+3 weeks+days, IQR: 24+1-27+0 weeks+days), who had tracheal aspirates collected during mechanical ventilation in their first day of life. CC16, cytokines, VEGF and matrix metalloproteinase-9 were measured in the tracheal aspirate and later correlated to results from advanced lung function measurements at 12 years of age., Results: Low levels of CC16 and high levels of the proinflammatory cytokines IL-1β and TNF-α in tracheal aspirate were associated with airway obstruction at school age but not with other lung function parameters. The correlation with airway obstruction was even stronger when the ratio between the respective proinflammatory cytokine and CC16 was used. In addition, low levels of VEGF and CC16 were associated with impaired diffusion capacity of the lung., Conclusions: An imbalance in inflammatory mediators and growth factors in the lungs at birth may have consequences for airway function and vasculature at school age in preterm born children., Competing Interests: Competing interests: CH has no conflict of interest. LB has received honoraria from Chiesi Pharma AB, Sweden, for being a member of the steering committee for the Nordic Neonatal Meetings and from AbbVie AB for lectures and for previously being a member of the steering committee for the NEOSPEX educational project. IHP holds stock/stock options in Premalux AB and has received honoraria from Baxter International for lectures. ET has received honoraria from Intramedic AB., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Several populations belonging to the genus Staurosirella have been observed in European rivers that were previously identified as Staurosirellapinnata . In light of the recent taxonomic revisions of the genus Staurosirella , the morphology of the unknown Staurosirella populations has been critically investigated using light and scanning electron microscopy. Following the comparison with previously described Staurosirella species, five taxa could not be identified using the currently available literature on the genus. These five taxa are described as new based on differences in valve outline; shape, size and structure of the apical pore fields; structure of the striae; and the presence, position and structure of the marginal spines. Two new species were described using historic collection material: Staurosirellabinodiformis sp. nov. and Svanheurckiana sp. nov. Two new species were observed in samples from rivers in Flanders: S.marginostriata sp. nov. and S.stoksiana sp. nov. whereas a fifth species was observed in rivers from Iceland: S.jonssoniana sp. nov. All new species are compared with similar Staurosirella species worldwide. Notes are added on their ecological preferences derived from both physicochemical data and the associated diatom flora., Competing Interests: The authors have declared that no competing interests exist., (Bart Van de Vijver, Valérie Peeters, Iris Hansen, Petra Ballings, Myriam de Haan.)

Objective: To determine the association between inpatient team continuity, defined as the maximum number of days the same student, resident, and attending worked together on the inpatient wards, and the academic performance of students in a pediatric block clerkship., Methods: We retrospectively identified students who rotated in the pediatric clerkship at a single institution from 2020 to 2022. We used multiple linear regression models to adjust for multiple confounders and used a one-way analysis of variance to compare adjusted outcomes across quartiles of inpatient team continuity., Results: A total of 227 students were included in the analysis. Students' preceptor ratings increased by 0.04 on a scale of 0-4 (95% confidence interval [CI] 0.01-0.06; p = .001), and their final pediatric grade increased by 0.02 on a scale of 0-4 (95% CI 0.01-0.02; p < .001) with each 1-day increase in inpatient team continuity. There was no statistically significant association between team continuity and shelf exam scores or observed structured clinical examination scores. Preceptor ratings and final clerkship grades increased across quartiles of team continuity, with the greatest increase being between the second, 6-7 days of continuity, and third, 8-10 days of continuity, quartiles., Conclusions: Increased inpatient team continuity is associated with students receiving higher preceptor ratings and achieving a higher final pediatric clerkship grade. While the mechanisms driving these associations remain unknown, the results add to the literature base supporting the importance of preceptor continuity in undergraduate medical education., (© 2024 Society of Hospital Medicine.)

Purpose of Review: The role of Sentinel Lymph Node Biopsy (SLNB) is pivotal in the contemporary staging of cutaneous melanoma. In this review, we examine advanced molecular testing platforms like gene expression profiling (GEP) and immunohistochemistry (IHC) as tools for predicting the prognosis of sentinel lymph nodes. We compare these innovative approaches with traditional staging assessments. Additionally, we delve into the shared genetic and protein markers between GEP and IHC tests and their relevance to melanoma biology, exploring their prognostic and predictive characteristics. Finally, we assess alternative methods to potentially obviate the need for SLNB altogether., Recent Findings: Progress in adjuvant melanoma therapy has diminished the necessity of Sentinel Lymph Node Biopsy (SLNB) while underscoring the importance of accurately identifying high-risk stage I and II melanoma patients who may benefit from additional anti-tumor interventions. The clinical application of testing through gene expression profiling (GEP) or immunohistochemistry (IHC) is gaining traction, with platforms such as DecisionDx, Merlin Assay (CP-GEP), MelaGenix GEP, and Immunoprint coming into play. Currently, extensive validation studies are in progress to incorporate routine molecular testing into clinical practice. However, due to significant methodological limitations, widespread clinical adoption of tissue-based molecular testing remains elusive at present., Summary: While various tissue-based molecular testing platforms have the potential to stratify the risk of sentinel lymph node positivity (SLNP), most suffer from significant methodological deficiencies, including limited sample size, lack of prospective validation, and limited correlation with established clinicopathological variables. Furthermore, the genes and proteins identified by individual gene expression profiling (GEP) or immunohistochemistry (IHC) tests exhibit minimal overlap, even when considering the most well-established melanoma mutations. However, there is hope that the ongoing prospective trial for the Merlin Assay may safely reduce the necessity for SLNB procedures if successful. Additionally, the MelaGenix GEP and Immunoprint tests could prove valuable in identifying high-risk stage I-II melanoma patients and potentially guiding their selection for adjuvant therapy, thus potentially reducing the need for SLNB. Due to the diverse study designs employed, effective comparisons between GEP or IHC tests are challenging, and to date, there is no study directly comparing the clinical utility of these respective GEP or IHC tests., Competing Interests: Declaration of Competing Interest J.K. has received honoraria from Bristol-Myers Squibb and Sanofi Genzyme and has received travel support from SUN Pharma and Pierre-Fabre Pharma, outside the submitted work. I.He. has received honoraria from Bristol-Myers Squibb and Sysmex, outside the submitted work. G.G. has received honoraria from Bristol-Myers Squibb and has research funding from Sanofi Genzyme, outside the submitted work. N.Z., T.Z., A.R., D.J.S. and F.A. report no conflicts of interest. I.Ha. has received honoraria from Bristol-Myers Squibb, outside the submitted work. D.S. Grants or contracts from any entity: Bristol Myers Squibb, Novartis, Roche, MSD Oncology, Array BioPharma/Pfizer. Consulting fees: Roche/Genentech, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Immunocore, Merck Serono, Array BioPharna, Pfizer, Pierre Fabre, Philogen, Regeneron, 4SC, Sanofi/Regeneron, NeraCare GmbH, Sun Pharma, InflarxGmbH, Ultimovacs, Sandoz. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi/Regeneron, Merck KGaA – speakers bureaus. Support for attending meetings and/or travel: Roche/Genentech, Bristol Myers Squibb, Merck Serono, Novartis, Merck Sharp & Dohme, Pierre Fabre, Sanofi/Regeneron. Participation on a Data Safety Monitoring Board or Advisory Board: Roche/Genentech, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, 4SC, Pierre Fabre, Sanofi/Regeneron, Nektar – Advisory Board. A.M.M.E has received honoraria for Scientific Advisory Board or Data Safety Monitoring Board participation from: Agenus, Atreca, Boehringer Ingelheim, BioNTech, Brenus, CatalYm, Ellipses, Galecto, GSK, IO Biotech, IQVIA, ISA Pharmaceuticals, Merck, MSD, Pfizer, Pierre Fabre, Sairopa, Sellas, SkylineDX, TogaTC, Trained Immunity TX. Equity: IOBiotech, Sairopa, SkylineDX. Lectures: BMS, MSDS.P. Grants or contracts from any entity: Almirall, ISDIN, La Roche Posay - To My Institution. Consulting fees: ISDIN, Almirall, La Roche Posay, MSD, Sanofi, Sun Pharma, Pfizer, Roche, Regeneron. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: ISDIN, La Roche Posay, Leo Pharma, Pfizer, Roche, Regeneron, BMS, Sun Pharma. Support for attending meetings and/or travel: Almirall. Participation on a Data Safety Monitoring Board or Advisory Board: Roche, Sanofi, Sun Pharma, Almirall, ISDIN, Pfizer, Novartis. A.H. reports grants and personal fees from Amgen, grants and personal fees from BMS, grants and personal fees from MerckPfizer, grants and personal fees from MSD/Merck, grants and personal fees from Philogen, grants and personal fees from Pierre Fabre, grants and personal fees from Regeneron, grants and personal fees from Roche, grants and personal fees from Sanofi-Genzyme, grants and personal fees from Novartis Pharma, grants and personal fees from Eisai, personal fees from Immunocore, grants and personal fees from Replimune, personal fees from Seagen, personal fees from IO Biotech, personal fees from Dermagnostix, personal fees from Incyte, grants and personal fees from NeraCare, personal fees from Highlight Therapeutics, grants from Huya Biosciences, personal fees from Kyowa Kirin, and personal fees from Iovance, outside the submitted work. C.G. is on the advisory board or has received honoraria from Almirall, Amgen, Beiersdorf, BioNTech, Bristol-Myers Squibb, Immunocore, Janssen, MSD Sharp & Dohme, Novartis, Pierre-Fabre Pharma, Roche, Sanofi Genzyme, SUN Pharma and Sysmex/Inostix, research funding from Novartis and Sanofi Genzyme, and travel support from Bristol-Myers Squibb, Pierre Fabre Pharma and SUN Pharma, outside the submitted work. C.G. is co-founder of Dermagnostix and Dermagnostix R&D., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background & Aim: Clinical trials supplementing the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) to preterm infants have shown positive effects on inflammation-related morbidities, but the molecular mechanisms underlying these effects are not fully elucidated. This study aimed to determine associations between DHA, AA, and inflammation-related proteins during the neonatal period in extremely preterm infants., Methods: A retrospective exploratory study of infants (n = 183) born below 28 weeks gestation from the Mega Donna Mega trial, a randomized multicenter trial designed to study the effect of DHA and AA on retinopathy of prematurity. Serial serum samples were collected after birth until postnatal day 100 (median 7 samples per infant) and analyzed for phospholipid fatty acids and proteins using targeted proteomics covering 538 proteins. Associations over time between LCPUFAs and proteins were explored using mixed effect modeling with splines, including an interaction term for time, and adjusted for gestational age, sex, and center., Results: On postnatal day one, 55 proteins correlated with DHA levels and 10 proteins with AA levels. Five proteins were related to both fatty acids, all with a positive correlation. Over the first 100 days after birth, we identified 57 proteins to be associated with DHA and/or AA. Of these proteins, 41 (72%) related to inflammation. Thirty-eight proteins were associated with both fatty acids and the overall direction of association did not differ between DHA and AA, indicating that both LCPUFAs similarly contribute to up- and down-regulation of the preterm neonate inflammatory proteome. Primary examples of this were the inflammation-modulating cytokines IL-6 and CCL7, both being negatively related to levels of DHA and AA in the postnatal period., Conclusions: This study supports postnatal non-antagonistic and potentially synergistic effects of DHA and AA on the inflammation proteome in preterm infants, indicating that supplementation with both fatty acids may contribute to limiting the disease burden in this vulnerable population., Clinical Registration Number: ClinicalTrials.gov (NCT03201588)., Competing Interests: Conflicts of interest The authors have no potential conflicts of interest relevant to this article to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The encoding of qubits in semiconductor spin carriers has been recognized as a promising approach to a commercial quantum computer that can be lithographically produced and integrated at scale 1-10 . However, the operation of the large number of qubits required for advantageous quantum applications 11-13 will produce a thermal load exceeding the available cooling power of cryostats at millikelvin temperatures. As the scale-up accelerates, it becomes imperative to establish fault-tolerant operation above 1 K, at which the cooling power is orders of magnitude higher 14-18 . Here we tune up and operate spin qubits in silicon above 1 K, with fidelities in the range required for fault-tolerant operations at these temperatures 19-21 . We design an algorithmic initialization protocol to prepare a pure two-qubit state even when the thermal energy is substantially above the qubit energies and incorporate radiofrequency readout to achieve fidelities up to 99.34% for both readout and initialization. We also demonstrate single-qubit Clifford gate fidelities up to 99.85% and a two-qubit gate fidelity of 98.92%. These advances overcome the fundamental limitation that the thermal energy must be well below the qubit energies for the high-fidelity operation to be possible, surmounting a main obstacle in the pathway to scalable and fault-tolerant quantum computation., (© 2024. The Author(s).)

Enteral supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA) in extremely preterm infants has shown beneficial effects on retinopathy of prematurity and pulmonary outcome whereas exclusive DHA supplementation has been associated with increased pulmonary morbidity. This secondary analysis evaluates pulmonary outcome in 204 extremely preterm infants, randomized to receive AA (100 mg/kg/day) and DHA (50 mg/kg/day) enterally from birth until term age or standard care. Pulmonary morbidity was primarily assessed based on severity of bronchopulmonary dysplasia (BPD). Serum levels of AA and DHA during the first 28 days were analysed in relation to BPD. Supplementation with AA:DHA was not associated with increased BPD severity, adjusted OR 1.48 (95 % CI 0.85-2.61), nor with increased need for respiratory support at post menstrual age 36 weeks or duration of oxygen supplementation. Every 1 % increase in AA was associated with a reduction of BPD severity, adjusted OR 0.73 (95 % CI 0.58-0.92). In conclusion, in this study, with limited statistical power, enteral supplementation with AA:DHA was not associated with an increased risk of pulmonary morbidity, but higher levels of AA were associated with less severe BPD. Whether AA or the combination of AA and DHA have beneficial roles in the immature lung needs further research., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Primary cutaneous T-cell lymphomas (CTCLs) are rare lymphoproliferative malignancies characterized by significant morbidity and mortality in advanced disease stages. As curative approaches apart from allogeneic stem cell transplantation are lacking, establishing new treatment options, especially combination therapies, is crucial., Methods: This retrospective study included 11 patients with SS or MF receiving therapy with mogamulizumab in combination with ECP from four European expert centers. The response rates in the skin and blood as well as treatment use and adverse events (AE) were described., Results: 8/11 patients (73%) showed an overall response (OR) in the skin. The mean mSWAT decreased from 98.2 ± 40.8 to 34.6 ± 23.8. The overall response rate (ORR) in the blood was 64% with two complete responses. During combination therapy, the mean number of Sézary cells decreased from 3365.3 × 10 6 /L before treatment to 1268.6 × 10 6 /L. The mean minimum known period without progress was 7.2 months in the skin and 7.6 months in the blood. The most common AEs were mogamulizumab-associated rash (MAR) (45.5%), anemia (27.3%), lymphocytopenia (27.8%), and infusion related reaction (16.7%). No AE led to treatment discontinuation., Conclusions: Our study presents the combination of mogamulizumab and ECP as an effective therapy in the blood and skin in CTCL with good tolerability, similar to mogamulizumab monotherapy.

Necrobiotic xanthogranuloma is a rare disease that is part of the non-Langerhans cell histiocytoses. It is characterized by yellowish skin lesions, which are typically periorbitally localized. Extracutaneous manifestations of all organs are possible and can cause potentially life-threatening complications. The disease also belongs to the facultative paraneoplasias and is often associated with paraproteinemia. These aspects should be considered regarding further diagnostics. Due to the rarity of the disease, there are no standardized guidelines for therapy so far. The combination of prednisolone and chlorambucil as well as intravenous immunoglobulins seem to be effective therapeutic options. We present four cases from our clinic as well as the current results of the literature in this mini-review and would like to highlight the therapeutic challenge as well as the need for the development of guidelines., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Objective: Blood cell populations, including red blood cells (RBC) unique to the extremely preterm (EPT) infant, are potentially lost due to frequent clinical blood sampling during neonatal intensive care. Currently, neonatal RBC population heterogeneity is not described by measurement of total haemoglobin or haematocrit. We therefore aimed to describe a subpopulation of large RBCs with hyper high haemoglobin content, >49 pg (Hyper-He) following EPT birth., Design: Prospective observational cohort study., Setting: Two Swedish study centres., Participants: Infants (n=62) born between gestational weeks 22 +0 to 26 +6 ., Methods: Prospective data (n=280) were collected from March 2020 to September 2022 as part of an ongoing randomised controlled trial. Blood was sampled from the umbilical cord, at postnatal day 1-14, 1 month, 40 weeks' postmenstrual age and at 3 months' corrected age., Results: At birth, there was a considerable inter-individual variation; Hyper-He ranging from 1.5% to 24.9% (median 7.0%). An inverse association with birth weight and gestational age was observed; Spearman's rho (CI) -0.38 (-0.63 to -0.07) and -0.39 (-0.65 to -0.05), respectively. Overall, Hyper-He rapidly decreased, only 0.6%-5.0% (median 2.2%) remaining 2 weeks postnatally. Adult levels (<1%) were reached at corresponding term age., Conclusion: Our results point to gestational age and birth weight-dependent properties of the RBC population. Future work needs to verify results by different measurement techniques and elucidate the potential role of differing properties between endogenous and transfused RBCs in relation to neonatal morbidities during this important time frame of child development., Trial Registration Number: NCT04239690., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)