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In a year marked by challenging market dynamics, the importance of ESG investments remains unwavering. But the wave of ESG regulations and requests generates a demand for more scalable ways to collect and analyze ESG data. The rise of AI could mark a turning point in an industry heavily burdened by reporting requirements, and unlock the true potential of ESG for businesses and investors alike.
Yes, they are. The securities services industry is at a tipping point of its digital transformation and will now see industry solutions to scale. We identify three fundamental drivers being adopted more broadly: cloud migration, data, and digitization. This triage also drives the scaling of Clearstream’s digital infrastructure D7, one of the leading digital infrastructures globally.
This study explores high-frequency cross-asset lead-lag relationships for various market microstructure dimensions. Utilizing data from stocks, futures, and exchange traded products, the findings uncover significant lead-lag patterns, particularly among fundamentally related instruments. Our results demonstrate that knowledge about lead-lag relationships can be leveraged for forecasting short-term changes in financial markets.
Nowadays, firms lack information to derive the share of wallet, a vital metric that identifies how much additional spending a firm could capture from each customer. However, decoding Blockchain data enables observing all transactions of each wallet, respectively customer, on the Ethereum NFT market. To shed light on the share of wallet, we analyzed 22.7 million transactions from over 1.3 million customers across eight competing firms on the Ethereum NFT market.
Beyond well-established difficulties with working memory in individuals with attention deficit hyperactivity disorder (ADHD), evidence is emerging that other memory processes may also be affected. We investigated, first, which memory processes show differences in adults and adolescents with ADHD in comparison to control participants, focusing on working and short-term memory, initial learning, interference, delayed and recognition memory. Second, we investigated whether ADHD severity, co-occurring depressive symptoms, IQ and physical fitness are associated with the memory performance in the individuals with ADHD.
We assessed 205 participants with ADHD (mean age 25.8 years, SD 7.99) and 50 control participants (mean age 21.1 years, SD 5.07) on cognitive tasks including the digit span forward (DSF) and backward (DSB), the Rey Auditory Verbal Learning Test (RAVLT), and the vocabulary and matrix reasoning subtests of the Wechsler Abbreviated Scale of Intelligence. Participants with ADHD were additionally assessed on ADHD severity, depression symptoms and cardiorespiratory fitness. A series of regressions were run, with sensitivity analyses performed when variables were skewed.
ADHD-control comparisons were significant for DSF, DSB, delayed and recognition memory, with people with ADHD performing less well than the control participants. The result for recognition memory was no longer significant in sensitivity analysis. Memory performance was not associated with greater ADHD or depression symptoms severity. IQ was positively associated with all memory variables except DSF. Cardiorespiratory fitness was negatively associated with the majority of RAVLT variables.
Individuals with ADHD showed difficulties with working memory, short-term memory and delayed memory, as well as a potential difficulty with recognition memory, despite preserved initial learning.
Targeted protein degradation (TPD) has recently emerged as an exciting new drug modality. However, the strategy of developing small molecule-based protein degraders has evolved over the past two decades and has now established molecular tags that are already in clinical use, as well as chimeric molecules, PROteolysis TArgeting Chimeras (PROTACs), based mainly on ligand systems developed for the two E3 ligases CRBN and VHL. The large size of the human E3 ligase family suggests that PROTACs can be developed by targeting a large diversity of E3 ligases, some of which have restricted expression patterns with the potential to design disease- or tissue-specific degraders. Indeed, many new E3 ligands have been published recently, confirming the druggability of E3 ligases. This review summarises recent data on E3 ligases and highlights the challenges in developing these molecules into efficient PROTACs rivalling the established degrader systems.
Highlights
• Pre-service teachershave stereotypes towards pupils with autism, Down syndrome and dyslexia.
• Pupils with Down syndrome, autism and dyslexia are associated with distinctive stereotypes.
• These stereotypes can be classified in three resp. four different dimensions.
Abstract
Stereotypes about pupils with special educational needs are prevalent both in society and among pre- and in-service teachers. However, little is known about the specific stereotypes pre-service teachers associate with autistic pupils, pupils with Down syndrome, and pupils with dyslexia. We explored these in two studies. Study 1 (N=13) involved qualitative interviews to identify potential stereotype content. Study 2 (N=213) used these findings to create a questionnaire to quantify these stereotypes. We found distinct stereotypes associated with all three groups of pupils. For successful inclusion, teachers must recognize the uniqueness of each pupil, including those with different diagnoses.
Research around the “glass escalator” demonstrates that men receive promotions faster than women in women-dominated occupations. However, it remains unclear how overall establishment composition affects the glass escalator. We use German longitudinal linked employer-employee data (LIAB) between 2012 and 2019 to examine how occupational and establishment gender composition shape gender differences in promotions to management. Establishment gender composition moderates the glass escalator, meaning women's mobility disadvantages in women-dominated jobs are most pronounced in men-dominated establishments. We hypothesize that changing occupational status is a central mechanism: When occupations mirror the composition of the establishment, their status increases locally. Higher occupational status offsets lower leadership expectations attributed to women and increases women's promotion odds relative to their male colleagues.
Highligthts
• Marburg virus infects and replicates in primary human proximal tubular cells (PTC).
• Transcriptome analyses at multiple time points revealed a profound inflammatory response by IFNα, -y and TNFα signaling.
• Among the strongly downregulated gene sets were targets of the transcription factors MYC and E2F, the G2M checkpoint, as well as oxidative phosphorylation.
• Importantly, the downregulated factors comprise PGC-1α, a key factor in mitochondrial biogenesis and renal energy homeostasis, to be substantially downregulated in MARV-infected PTC.
• Our results suggest inflammation-induced changes in tubular energy metabolism as a possible factor in MARV-associated tubular dysfunction.
Abstract
Marburg virus, a member of the Filoviridae, is the causative agent of Marburg virus disease (MVD), a hemorrhagic fever with a case fatality rate of up to 90 %. Acute kidney injury is common in MVD and is associated with increased mortality, but its pathogenesis in MVD remains poorly understood. Interestingly, autopsies show the presence of viral proteins in different parts of the nephron, particularly in proximal tubular cells (PTC). These findings suggest a potential role for the virus in the development of MVD-related kidney injury. To shed light on this effect, we infected primary human PTC with Lake Victoria Marburg virus and conducted transcriptomic analysis at multiple time points. Unexpectedly, infection did not induce marked cytopathic effects in primary tubular cells at 20 and 40 h post infection. However, gene expression analysis revealed robust renal viral replication and dysregulation of genes essential for different cellular functions. The gene sets mainly downregulated in PTC were associated with the targets of the transcription factors MYC and E2F, DNA repair, the G2M checkpoint, as well as oxidative phosphorylation. Importantly, the downregulated factors comprise PGC-1α, a well-known factor in acute and chronic kidney injury. By contrast, the most highly upregulated gene sets were those related to the inflammatory response and cholesterol homeostasis. In conclusion, Marburg virus infects and replicates in human primary PTC and induces downregulation of processes known to be relevant for acute kidney injury as well as a strong inflammatory response.
Background: Urachal cancer (UrC) is a rare disease with limited availability of representative incidence and clinical data. Although, the prevalence is accounting for less than 1% of bladder tumors, the 5-year survival rate is around only 50% for patients with resectable tumors, and even worse for patients with metastatic disease. Due to the lack of comprehensive prospective studies, our current knowledge of UrC is still limited.
Objective: The present study aimed to summarize the available registry-based studies with unselected UrC patients to evaluate its incidence and clinicopathological characteristics.
Material and methods: We conducted a systematic literature search of registry-based UrC publications on the 15th of May 2023 in 5 databases, which identified 4,748 publications. After duplicate removal and selection by 2 independent investigators, 6 publications proved to be appropriate for the final meta-analysis. Estimated incidence and clinicopathological parameters were extracted.
Results: Estimated incidence ranged between 0.022 and 0.060/ 100.000 person-years, with the highest occurrence in Japan and the lowest in Canada, while the random effect model calculated an overall incidence rate of 0.04 (95%CI: 0.03–0.05) 100.000 person-years. The median age at first diagnosis was 60 years (range: 58–64). The female to male ratio was 2:3. Lymph node or distant metastases were present in 9% and 14% of patients. The predominant tumour type was adenocarcinoma (86%) followed by urothelial carcinoma (12%) and squamous cell carcinoma (2%). The 5-year survival rate was 51.0% with 95%CI: 45.2–57.4.
Conclusions: Our study provides an up-to-date comparison of estimated incidence rates between 6 countries of 3 continents based on rigorously selected registry-based studies. The results suggest low incidence rates for UrC with considerable geographic differences. The present meta-analysis provides unbiased registry-based data on the incidence, clinicopathological parameters and survival of UrC.