FINCA syndrome [MIM: 618278] is an autosomal recessive multisystem disorder characterized by fibrosis, neurodegeneration and cerebral angiomatosis. To date, 13 patients from nine families with biallelic NHLRC2 variants have been published. In all of them, the recurrent missense variant p.(Asp148Tyr) was detected on at least one allele. Common manifestations included lung or muscle fibrosis, respiratory distress, developmental delay, neuromuscular symptoms and seizures often followed by early death due to rapid disease progression.Here, we present 15 individuals from 12 families with an overlapping phenotype associated with nine novel NHLRC2 variants identified by exome analysis. All patients described here presented with moderate to severe global developmental delay and variable disease progression. Seizures, truncal hypotonia and movement disorders were frequently observed. Notably, we also present the first eight cases in which the recurrent p.(Asp148Tyr) variant was not detected in either homozygous or compound heterozygous state.We cloned and expressed all novel and most previously published non-truncating variants in HEK293-cells. From the results of these functional studies, we propose a potential genotype-phenotype correlation, with a greater reduction in protein expression being associated with a more severe phenotype.Taken together, our findings broaden the known phenotypic and molecular spectrum and emphasize that NHLRC2-related disease should be considered in patients presenting with intellectual disability, movement disorders, neuroregression and epilepsy with or without pulmonary involvement.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy that derives from precursors of plasmacytoid dendritic cells and is characterized by disseminated, erythematous or bluish-livid plaques or nodi. Because of the disease's rarity the diagnosis and treatment still pose a significant challenge. We present a case of a patient with BPDCN and show clinical and diagnostic characteristics as well as potential treatment regimes.

Objectives: The aims are (a) assessment of the prevalence of psychosocial emergencies in the emergency department (ED), (b) determination of the proportion of cases not coded as diagnosis (unreported cases), and (c) characterization of identified patients.Methods: In a retrospective study, psychosocial emergencies in one week were identified from routine documentation of the central ED of the Charite - Universitatsmedizin Berlin, Charite Campus Mitte (CCM). After exclusion of planned admitted cases, 862 patients were included in the study. The identified psychosocial emergencies were descriptively analyzed with regard to their sociodemographic and clinical characteristics and compared with other emergencies.Results: The prevalence of psychosocial emergencies in the reported period was 11.9% (n = 103). A large proportion of psychosocial emergencies were not coded (35.9%) or not fully coded (20.4%) as an ICD diagnosis (unreported cases). There was a statistically relevant difference in gender distribution with a significantly higher proportion of males among psychosocial emergencies (70.9%) compared to other emergencies (50.7%; p < 0.0001). The two most common treatment causes among psychosocial emergencies were substance abuse (66.0%) and homelessness (20.4%).Conclusions: This study shows a relevant proportion of psychosocial emergencies among all treatments in ED routine data and a high proportion of cases not captured in the coded diagnoses. EDs thus represent an important point of contact for vulnerable patient groups but standardized screening and identification are still lacking.

The increasing use of artificial intelligence (AI) in medicine is associated with new ethical challenges and responsibilities. However, special considerations and concerns should be addressed when integrating AI applications into medical education, where healthcare, AI, and education ethics collide. This commentary explores the biomedical ethical responsibilities of medical institutions in incorporating AI applications into medical education by identifying potential concerns and limitations, with the goal of implementing applicable recommendations. The recommendations presented are intended to assist in developing institutional guidelines for the ethical use of AI for medical educators and students.

Background and purpose: The study compares early outcomes after simultaneous and staged knee arthroplasty in patients with bilateral knee osteoarthritis (OA) to evaluate whether simultaneous bilateral TKA shows comparable early outcomes and complication rates to staged bilateral TKA. Methods: A retrospective cohort study including all patients scheduled for primary TKA for bilateral knee OA (n = 127) was conducted. Patients received either simultaneous (n = 53, 41.7%) or staged (n = 74, 58.3%) bilateral TKA by a single, high-volume surgeon-depending on their individual preference. Demographic data, haemoglobin drop (Hb), length of stay (LOS), operation time, 30-day complication rate and achievement of rehabilitation key points were evaluated. Results: There was no difference between the groups concerning age, sex, BMI or complication rate. ASA scoring was better in the simultaneous group [2.2, (15.1% ASA 1, 49.1% ASA 2, 35.8% ASA 3) vs. 2.4 (2.7% ASA 1, 51.4% ASA 2, 45.9% ASA 3)]. Average LOS was 7.8 +/- 2.1 days for simultaneous TKA, 7.4 +/- 1.7 days for single procedure of staged group (p < 0.453) and 14.7 +/- 3.1 days if combined (p < 0.001). Cumulative Hb loss was significantly higher in the staged group (3.8 +/- 1.2 g/dl vs. 2.4 +/- 0.8 g/dl, p < 0.001). Detailed comparison of early outcome parameters between staged and simultaneous procedure depending on ASA score only revealed slightly slower assessment of stairs (p < 0.001) and increased Hb drop per surgery in case of simultaneous procedure (p < 0.011) if ASA score was >= 2. Only patients scored ASA 3 demonstrated a significant longer LOS per procedure in simultaneous group (8.5 +/- 2.4 vs.7.3 +/- 1.6 days, p = 0.034). Interpretation: Simultaneous bilateral TKA results in comparable early outcome and complication rate than staged bilateral procedure-even for patients scored ASA 3.

Purpose: The aim of this study was to compare early outcomes after simultaneous and staged hip arthroplasty (THA) in patients with bilateral symptomatic pathology.Methods: We conducted a retrospective cohort study including all patients scheduled for primary THA for bilateral hip osteoarthritis (OA, n = 290). Patients either received simultaneous (n = 152, 52.4%) or staged (n = 138, 47.6%) bilateral THA based on individual preference. All operations (n = 428) were performed by one single, high-volume surgeon. Demographic data (e.g., age, ASA score) as well as perioperative parameters (haemoglobin drop (Hb), red blood cell transfusion, length of stay (LOS), operation time, six week complication rate and achievement of inpatient rehabilitation key points) were evaluated.Results: Patients in the simultaneous bilateral THA group were younger (62.8 & PLUSMN; 8.9 vs. 65 & PLUSMN; 9.7 years, p = 0.022) and had lower ASA scores (1.8, (34.2% ASA 1, 55.3% ASA 2, 37.2% ASA 3) vs. 2.0 (18.8% ASA 1, 61.6% ASA 2, 19.6% ASA 3)) than the staged group. While the average LOS was 7.1 & PLUSMN; 1.7 days for simultaneous bilateral THA, the combined LOS for the staged group was 12.9 & PLUSMN; 2.4 days (p < 0.001). The cumulative operation time in the simultaneous bilateral THA group was 61.1 & PLUSMN; 11.5 min and 57.6 & PLUSMN; 7.3 min in the staged group (p < 0.015). Cumulative Hb loss was significantly higher in the staged group (2.1 & PLUSMN; 7.2 g/dl vs. 3.7 & PLUSMN; 1.3 g/dl, p < 0.001). No significant differences were found concerning the complication rate or early inpatient rehabilitation.Conclusion: Simultaneous bilateral hip arthroplasty in patients with symptomatic bilateral hip osteoarthritis is as safe and successful as a staged procedure if performed by a high-volume surgeon.

The leptin-melanocortin pathway is playing a pivotal role for central body weight regulation. The melanocortin 4 receptor (MC4R) is essential to induce satiety after activation by the endogenous ligands α-/β-melanocyte-stimulating hormone. The relevance of biased signaling is exemplified by an MC4R agonist, which has been approved for the treatment of rare forms of monogenic obesity. Here biased signaling is discussed as new option to develop drugs with an improved safety profile.

Autoimmune encephalitides are seldom diseases. How rare they actually are, however, is not known. The low incidence combined with the problematic identification may dampen efforts of neurologists, to identify patients with unclear symptoms as suffering from autoimmune encephalitis. Here, we aim to obtain a better estimate, how many patients with autoimmune disorders should be expected among 100 inpatients in a conventional neurological department. From a total number of 2603 non-stroke patients attended in a 2-year period (2018-2019) 460 CSFs were obtained. From this collection 187 samples (40.7%, > 500 sections) could be analyzed with our immunocytochemical technique. Autoreactive antibodies were detected in 102 (55%) of these 187 CSF samples. Certainly, the presence of autoreactive antibodies does not necessarily indicate that the patient suffers from an autoimmune disease. Our data indicate that from roughly 2000 patients during 1 year about 125 patients with autoreactive CSF antibodies should be expected in a conventional neurological department. This represents the about 35-fold value of what is generally expected at present. Being aware of this high incidence may intensify the efforts of neurologist to identify patients with any type of autoimmune encephalitis. This will be beneficial for patients, because they often profit from immunomodulatory therapy. Interestingly, some CFSs from our patients react with the CA2 subdivision of the hippocampus. While long neglected, recent research places this area into an important position to influence hippocampal network physiology. Autoreactive antibodies in the CSF may disturb the function of CA2 neurons, thereby explaining some neuropsychiatric symptoms in patients with autoimmune encephalitides.

Mental health discourse has gained prominence in public media, significantly influencing societal perceptions. This study explores the application of Natural Language Processing (NLP) techniques to analyze the representation of mental health in news media texts. The complex interplay between media representation and public understanding of mental health requires advanced analytical tools. NLP offers promising avenues for unpacking these narratives but faces challenges in capturing the nuances of mental health discourse. We employ a scoping review to examine several NLP applications, including sentiment analysis, topic modeling, and bias detection. Our study compares news media to social media, highlighting the unique linguistic challenges of formal journalistic language. The analysis reveals significant limitations of current NLP techniques when applied to mental health news coverage. We uncover significant biases and accuracy issues in sentiment analysis of mental health content across different media platforms. Our findings underscore the need for specialized NLP techniques in mental health news analysis. We propose ten recommendations for tailored NLP approaches that provide critical insights for researchers, policymakers, and media professionals. This work aims to improve mental health communication strategies and promote more nuanced, effective public discourse and media coverage.

Background: Until now the long-term consequences of the medical treatment for bipolar disorder have barely been examined, especially the consequences with respect to cognitive impairment and dementia. Some studies show signs that some treatment options have a better effect on the brain than others. This review summarizes the current state of research. Objective: The effects of long-term consequences of lithium, valproic acid, carbamazepine and antipsychotic agents on the development of dementia or cognitive impairments in patients with bipolar disorder were investigated. Methods: A systematic literature search was carried out in the PubMed data base from May to July 2022. Results: The majority of studies showed that lithium has a neuroprotective effect and can lower the risk of developing dementia, whereas an increased risk was found in patients taking valproic acid. There are only very few studies that deal with antipsychotic medication and the long-term consequences concerning dementia. Conclusion: Lithium should be recommended for the long- term treatment of bipolar disorder. Valproic acid should not or carefully be used as it can affect the risk of developing dementia. With respect to antipsychotics there is no recommendation as more studies are needed to evaluate the long-term consequences.

Epigenetic regulators are multiprotein complexes that modify chromatin architecture to control gene expression in response to developmental and environmental cues. These complexes function in a highly coordinated manner, often collaborating with various accessory proteins to precisely regulate the dynamic nature of chromatin states. However, our understanding of how these core histone-modifying regulators co-evolved with accessory proteins during plant evolution remains limited. Therefore, in this review, we summarize the evolution of major histone modification regulators, with a focus on Polycomb group complexes and their associated accessory proteins. We discuss how accessory proteins have evolved to modulate the activity of conserved core components, supporting key innovations during plant evolution. Lastly, we highlight the role of accessory proteins in mediating crosstalk between histone-modifying complexes, emerging as key evolutionary factors that shape the epigenetic landscape and influence plant development and environmental adaptation.

Multimodal remote sensing data, including spectral and LiDAR or photogrammetry, is crucial for achieving satisfactory land-use/land-cover classification results in urban scenes. So far, most studies have been conducted in a 2-D context. When 3-D information is available in the dataset, it is typically integrated with the 2-D data by rasterizing the 3-D data into 2-D formats. Although this method yields satisfactory classification results, it falls short in fully exploiting the potential of 3-D data by restricting the model’s ability to learn 3-D spatial features directly from raw point clouds. In addition, it limits the generation of 3-D predictions, as the dimensionality of the input data has been reduced. In this study, we propose a fully 3D-based method that fuses all modalities within the 3-D point cloud and employs a dedicated dual-branch Transformer model to simultaneously learn geometric and spectral features. To enhance the fusion process, we introduce a cross-attention-based mechanism that fully operates on 3-D points, effectively integrating features from various modalities across multiple scales. The purpose of cross-attention is to allow one modality to assess the importance of another by weighing the relevant features. We evaluated our method by comparing it against both 3-D and 2-D methods using the 2018 IEEE GRSS Data Fusion Contest (DFC2018) dataset. Our findings indicate that 3-D fusion delivers competitive results compared to 2-D methods and offers more flexibility by providing 3-D predictions. These predictions can be projected onto 2-D maps, a capability that is not feasible in reverse. In addition, we evaluated our method on different datasets, specifically the ISPRS Vaihingen 3-D and the IEEE DFC2019.

This study explores the voting potential for the new left-authoritarian German party, Bündnis Sahra Wagenknecht (BSW). We focus on the congruence regarding three policy dimensions. We identify three primary issue dimensions underlying the agreement with BSW’s policies: cultural issues, where BSW advocates for conservative policies; economic issues, emphasising left-wing stances on redistribution and the structure of the economic system; and foreign policy issues, focusing on ‘peace-oriented’ strategies, scepticism of NATO and the USA, and inclusion of Russia in European security frameworks. We build our analytical framework on the Michigan model and the proximity model of voting. Our findings reveal that socio-demographic characteristics – age, education, gender, and east/west location – influence the congruence with BSW’s policies. Older voters, less educated individuals, women, and east Germans exhibit greater congruence with BSW’s ideological stances across all three dimensions. The east-west divide is particularly pronounced. We demonstrate that congruence on the three issue dimensions significantly predicts the propensity to vote (PTV) for BSW. Once we introduce policy congruence to the models, all socio-demographic factors, including an east/west variable, are not statistically significant anymore. Our results support the classic “funnel of causality”, where socio-demographics shape political attitudes, which in turn drive voting behaviour. Contrary to assumptions that BSW’s appeal is related to a vague notion of “east Germanness,” our results indicate that ideological proximity explains the party’s higher electoral potential in east Germany.

Background and purpose: C-reactive protein serves as a marker of inflammation and is linked to depression in the general population. We aimed to assess whether elevated baseline levels of high-sensitivity C-reactive protein (hs-CRP) are associated with depressive symptoms over time in a prospective cohort of mild-to-moderate first-ever ischemic stroke patients.Methods: Data were obtained from the Prospective Cohort with Incident Stroke Berlin (NCT01363856). Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) at three annual follow-up points. We assessed the association of elevated levels of hs-CRP with CES-D scores over time via linear mixed models. In a subgroup analysis, we explored an interaction effect with sex.Results: We included 585 ischemic stroke patients with baseline data on CRP levels. The mean age was 67 (13 SD), 39% (n = 226) were female, and the median National Institutes of Health Stroke Scale (NIHSS) was 3 (IQR 1-4). Twenty percent of survivors showed evidence for depressive symptoms one year after stroke with CES-D >= 16, 21% at year two, and 17% at year three. Higher log-transformed baseline hs-CRP levels were associated with higher CES-D Scores over time in the adjusted linear mixed model (beta = 1.28; (95% CI 0.22-2.34)). The subgroup analysis revealed an interaction effect of hs-CRP on depressive symptoms in women (beta = 2.33; (95% CI 0.71-3.95)).Conclusion: In our cohort with mild-to-moderate first-ever ischemic stroke patients, hs-CRP levels were associated with more depressive symptoms over time, with an interaction effect for the female sex.Study registration: https://clinicaltrials.gov; Unique identifier: NCT01363856.

The concept of the ‘nomad’ in central Eurasian archaeology and anthropology is highly problematic. Nomadic people and their way of life, mobile pastoralism, have consistently been characterised by what they lack in opposition to settled agriculturalists. This has resulted in the depiction of nomads through time as entirely dependent on their environment, living in politically unstable ‘tribes’ and constantly raiding their sedentary neighbours. This essay deconstructs these long-standing assumptions which are inherent to Western and Russo-Soviet scholarship about so-called nomads. Instead, it highlights new approaches which focus on the diversity and resilience of past mobile pastoralists in central Eurasia. The archaeological project at Begash, Kazakhstan, is presented and discussed as a case study. Ultimately, the concept of the nomad proves to be a paradox which should be abandoned in favour of more relational definitions and approaches.

In recent years, there has been an increasing quest in improving our understanding of the neurocognitive deficits underly i n g adult attention-deficit/hyperactivity disorder (ADHD). Current statistical manuals of psychiatric disorders emphasize inattention and hyperactivity-impulsivity symptoms, but empirical studies have also shown consistent alterations in inhibitory control. To date, there is no established neuropsychological test to assess inhibitory control deficits in adult ADHD. A common paradigm for assessing response inhibition is the stop-signal task (SST). Following PRISMA-selection criteria, our systematic review and meta-analysis integrated the findings of 26 publications with 27 studies examining the SST in adult ADHD. The meta-analysis, which included 883 patients with adult ADHD and 916 control participants, revealed reliable inhibitory con-trol deficits, as expressed in prolonged SST response times, with a moderate effect size g = 0.51 (95% CI: 0.376-0.644,p < 0.0001). The deficits were not moderated by study quality, sample characteristics or clinical parameters, suggesting that they may be a phenotype in this disorder. The analyses of secondary outcome measures revealed greater SST omission errors and reduced go accuracy in patients, indicative of altered sustained attention. However, only few (N< 10) studies were available for these measures. Our meta-analysis suggests that the SST, in conjunction with other tests and questionnaires, could become a valuable tool for assessing inhibitory control deficits in adult ADHD.

Background: The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic causes a high burden of acute and long-term morbidity and mortality worldwide despite global efforts in containment, prophylaxis, and therapy. With unprecedented speed, the global scientific community has generated pivotal insights into the pathogen and the host response evoked by the infection. However, deeper characterization of the pathophysiology and pathology remains a high priority to reduce morbidity and mortality of coronavirus disease 2019 (COVID-19).Methods: NAPKON-HAP is a multi-centered prospective observational study with a long-term follow-up phase of up to 36 months post-SARS-CoV-2 infection. It constitutes a central platform for harmonized data and biospecimen for interdisciplinary characterization of acute SARS-CoV-2 infection and long-term outcomes of diverging disease severities of hospitalized patients.Results: Primary outcome measures include clinical scores and quality of life assessment captured during hospitalization and at outpatient follow-up visits to assess acute and chronic morbidity. Secondary measures include results of biomolecular and immunological investigations and assessment of organ-specific involvement during and post-COVID-19 infection. NAPKON-HAP constitutes a national platform to provide accessibility and usability of the comprehensive data and biospecimen collection to global research.Conclusion: NAPKON-HAP establishes a platform with standardized high-resolution data and biospecimen collection of hospitalized COVID-19 patients of different disease severities in Germany. With this study, we will add significant scientific insights and provide high-quality data to aid researchers to investigate COVID-19 pathophysiology, pathology, and chronic morbidity.

The status and origin of the species Pelargonium adulterinum L'Hér. (Geraniaceae) from the Western Cape of South Africa and its correct authorship are discussed. It is shown that L'Héritier not Aiton is the author of the name. A lectotype originating from L'Héritier's herbarium is designated on a collection kept in Candolle's herbarium (G-DC). The later name P. semitrilobum Jacq. is shown to be synonymous and a lectotype is designated originating from Jacquin's collections now in Vienna (W).

Background: Routine data such as claims data and health care documentation data are of increasing relevance in health services research—also in the field of general practice and family medicine. An increasing number of articles using these kind of data highlights the increasing relevance. Thus, it is essential for general practitioners (GPs) to know the strength and weaknesses of studies using routine data. Aim: The goal if this article is to empower readers to critically appraise articles based on routine data in a systematic and criteria-based fashion. Materials and methods: We used available guidelines and recommendations, a selective literature review, and our own expertise. Results: An advantage of routine data is that they are less cost intensive than primary data acquisition in prospective studies. Routine data have usually a lower selection bias; hence, they represent the reality of health care better than primarily acquired data. Another advantage is the high case numbers in routine data, which allows subgroup analyses even for low prevalent patient groups. Limitations are the restricted quality and validity of routine data. These limitations have to be addressed by measures of quality assurance such as internal and external validation. Conclusion: Routine data analyses are an important method in health care research. These analyses are especially good in researching everyday health care and analyzing subgroups with low prevalence. Results fromroutine data analyses should be reported transparently including the limitations of the study.