Post-COVID recovery is faster after an infection with the SARS-CoV-2 Omicron variant: a population-based cohort study.

Purpose: Post-COVID-19 condition (PCC) poses a substantial burden to affected individuals, health care systems, and society as a whole. We examined factors associated with recovery from PCC, focusing on the vaccination status prior to infection and the virus variant.

Methods: Our analyses are based on the population-based cohort study for digital health research in Germany (DigiHero).

Differential associations between SARS-CoV-2 infection, perceived burden of the pandemic and mental health in the German population-based cohort for digital health research.

Understanding the potential adverse effects of the COVID-19-pandemic on mental health remains a challenge for public health. Differentiation between potential consequences of actual infection with SARS-CoV-2 and the subjective burden of the pandemic due to measures and restrictions to daily life still remains elusive. Therefore, we investigated the differential association between infection with SARS-Cov-2 and subjective burden of the pandemic in a study cohort of 7601 participants from the German population-based cohort for digital health research (DigiHero), who were recruited between March 4th and April 25th 2022.

Transplant-associated thrombotic microangiopathy in pediatrics: incidence, risk factors, therapeutic options, and outcome based on data from a single center.

Background: Transplant-associated thrombotic microangiopathy (TA-TMA) is a critical complication of hematopoietic stem cell transplantation. Awareness about TA-TMA has increased in recent years, resulting in the implementation of TA-TMA screening in most centers.

Methods: Retrospective analysis of children who underwent autologous or allogeneic hematopoietic stem cell transplantation at our center between January 2018 and December 2022 was conducted to evaluate the incidence, clinical features, and outcomes of TA-TMA following the administration of different therapeutic options.

Insights into early recovery from Long COVID-results from the German DigiHero Cohort.

65 million people worldwide are estimated to suffer from long-term symptoms after their SARS-CoV-2 infection (Long COVID). However, there is still little information about the early recovery among those who initially developed Long COVID, i.e.

SARS-CoV-2 vaccination may mitigate dysregulation of IL-1/IL-18 and gastrointestinal symptoms of the post-COVID-19 condition.

The rapid development of safe and effective vaccines helped to prevent severe disease courses after SARS-CoV-2 infection and to mitigate the progression of the COVID-19 pandemic. While there is evidence that vaccination may reduce the risk of developing post-COVID-19 conditions (PCC), this effect may depend on the viral variant. Therapeutic effects of post-infection vaccination have been discussed but the data for individuals with PCC remains inconclusive.

Regional Differences in Uptake of Vaccination against COVID-19 and Influenza in Germany: Results from the DigiHero Cohort.

During the COVID-19 pandemic in Germany, vaccination uptake exhibited considerable regional disparities. To assess the factors contributing to this variation, we examined the association of sociodemographic variables with COVID-19, COVID-19 booster, and influenza vaccination status within a cohort of 37,078 participants from 13 German federal states in the digital health cohort study commonly known as DigiHero. Our findings revealed variations in vaccination rates based on sociodemographic factors.

Association between virus variants, vaccination, previous infections, and post-COVID-19 risk.

Objectives: The SARS-CoV-2 Omicron variant has spread rapidly and has been the dominant variant since 2022. The course of acute infection, in a vaccinated population, with Omicron is milder compared with earlier variants. However, little is known about how the occurrence of long-term symptoms after Omicron infection compared with other variants is modulated by previous infections and/or vaccinations.

Anxiety, depressive symptoms, and distress over the course of the war in Ukraine in three federal states in Germany.

Introduction: The Russian invasion of Ukraine and the resulting consequences are in the center of political discussions, media, and likely individual thinking of the population in Germany. Yet, the impact of this prolonged exposure on mental health is not known hitherto.

Methods: Using the population based cohort study DigiHero from three federal states (Saxony-Anhalt, Saxony, and Bavaria), we assessed anxiety levels (GAD-7), depressive symptoms (PHQ-9), and distress (modified PDI) in the first weeks of war and 6 months later.

A noncanonical enzymatic function of PIWIL4 maintains genomic integrity and leukemic growth in AML.

RNA-binding proteins (RBPs) form a large and diverse class of factors, many members of which are overexpressed in hematologic malignancies. RBPs participate in various processes of messenger RNA (mRNA) metabolism and prevent harmful DNA:RNA hybrids or R-loops. Here, we report that PIWIL4, a germ stem cell-associated RBP belonging to the RNase H-like superfamily, is overexpressed in patients with acute myeloid leukemia (AML) and is essential for leukemic stem cell function and AML growth, but dispensable for healthy human hematopoietic stem cells.

Mental health in Germany in the first weeks of the Russo-Ukrainian war.

Background: In the connected world, although societies are not directly involved in a military conflict, they are exposed to media reports of violence.

Aims: We assessed the effects of such exposures on mental health in Germany during the military conflict in Ukraine.

Method: We used the German population-based cohort for digital health research, DigiHero, launching a survey on the eighth day of the Russo-Ukrainian war.

YBX1 mediates translation of oncogenic transcripts to control cell competition in AML.

Persistence of malignant clones is a major determinant of adverse outcome in patients with hematologic malignancies. Despite the fact that the majority of patients with acute myeloid leukemia (AML) achieve complete remission after chemotherapy, a large proportion of them relapse as a result of residual malignant cells. These persistent clones have a competitive advantage and can re-establish disease.

Mutational mechanisms shaping the coding and noncoding genome of germinal center derived B-cell lymphomas.

B cells have the unique property to somatically alter their immunoglobulin (IG) genes by V(D)J recombination, somatic hypermutation (SHM) and class-switch recombination (CSR). Aberrant targeting of these mechanisms is implicated in lymphomagenesis, but the mutational processes are poorly understood. By performing whole genome and transcriptome sequencing of 181 germinal center derived B-cell lymphomas (gcBCL) we identified distinct mutational signatures linked to SHM and CSR.

YBX1 Indirectly Targets Heterochromatin-Repressed Inflammatory Response-Related Apoptosis Genes through Regulating CBX5 mRNA.

Medulloblastomas arise from undifferentiated precursor cells in the cerebellum and account for about 20% of all solid brain tumors during childhood; standard therapies include radiation and chemotherapy, which oftentimes come with severe impairment of the cognitive development of the young patients. Here, we show that the posttranscriptional regulator Y-box binding protein 1 (YBX1), a DNA- and RNA-binding protein, acts as an oncogene in medulloblastomas by regulating cellular survival and apoptosis. We observed different cellular responses upon YBX1 knockdown in several medulloblastoma cell lines, with significantly altered transcription and subsequent apoptosis rates.

RNA-Binding Proteins in Acute Leukemias.

Acute leukemias are genetic diseases caused by translocations or mutations, which dysregulate hematopoiesis towards malignant transformation. However, the molecular mode of action is highly versatile and ranges from direct transcriptional to post-transcriptional control, which includes RNA-binding proteins (RBPs) as crucial regulators of cell fate. RBPs coordinate RNA dynamics, including subcellular localization, translational efficiency and metabolism, by binding to their target messenger RNAs (mRNAs), thereby controlling the expression of the encoded proteins.

Pediatric ALL relapses after allo-SCT show high individuality, clonal dynamics, selective pressure, and druggable targets.

Survival of patients with pediatric acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-SCT) is mainly compromised by leukemia relapse, carrying dismal prognosis. As novel individualized therapeutic approaches are urgently needed, we performed whole-exome sequencing of leukemic blasts of 10 children with post-allo-SCT relapses with the aim of thoroughly characterizing the mutational landscape and identifying druggable mutations. We found that post-allo-SCT ALL relapses display highly diverse and mostly patient-individual genetic lesions.

Facing the large variety of life-limiting conditions in children.

Life-limiting conditions in children in specialized pediatric palliative care (PPC) are manifold. The "Together for Short Lives" (TfSL) association established four disease categories, which represent the most common illness trajectories. Better understanding the palliative care needs and symptoms of children within these TfSL groups will result in improved anticipation of clinical problems and tailored care.

Molecular Approaches to Treating Pediatric Leukemias.

Over the past decades, striking progress has been made in the treatment of pediatric leukemia, approaching 90% overall survival in children with acute lymphoblastic leukemia (ALL) and 75% in children with acute myeloid leukemia (AML). This has mainly been achieved through multiagent chemotherapy including CNS prophylaxis and risk-adapted therapy within collaborative clinical trials. However, prognosis in children with refractory or relapsed leukemia remains poor and has not significantly improved despite great efforts.

Fragile X mental retardation protein protects against tumour necrosis factor-mediated cell death and liver injury.

Objective: The Fragile X mental retardation (FMR) syndrome is a frequently inherited intellectual disability caused by decreased or absent expression of the FMR protein (FMRP). Lack of FMRP is associated with neuronal degradation and cognitive dysfunction but its role outside the central nervous system is insufficiently studied. Here, we identify a role of FMRP in liver disease.

An alternative approach to establishing unbiased colorectal cancer risk estimation in Lynch syndrome.

Purpose: Biallelic pathogenic variants in the mismatch repair (MMR) genes cause a recessive childhood cancer predisposition syndrome known as constitutional mismatch repair deficiency (CMMRD). Family members with a heterozygous MMR variant have Lynch syndrome. We aimed at estimating cancer risk in these heterozygous carriers as a novel approach to avoid complicated statistical methods to correct for ascertainment bias.

Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma.

Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation.

Mutated SON putatively causes a cancer syndrome comprising high-risk medulloblastoma combined with café-au-lait spots.

Medulloblastoma is the most frequent malignant brain tumor in childhood. This highly malignant neoplasm occurs usually before 10 years of age and more frequently in boys. The 5-year event-free survival rate for high-risk medulloblastoma is low at 62% despite a multimodal therapy including surgical resection, radiation therapy and chemotherapy.

Deciphering human ribonucleoprotein regulatory networks.

RNA-binding proteins (RBPs) control and coordinate each stage in the life cycle of RNAs. Although in vivo binding sites of RBPs can now be determined genome-wide, most studies typically focused on individual RBPs. Here, we examined a large compendium of 114 high-quality transcriptome-wide in vivo RBP-RNA cross-linking interaction datasets generated by the same protocol in the same cell line and representing 64 distinct RBPs.

Transcriptome-wide analysis uncovers the targets of the RNA-binding protein MSI2 and effects of MSI2's RNA-binding activity on IL-6 signaling.

The RNA-binding protein Musashi 2 (MSI2) has emerged as an important regulator in cancer initiation, progression, and drug resistance. Translocations and deregulation of the gene are diagnostic of certain cancers, including chronic myeloid leukemia (CML) with translocation t(7;17), acute myeloid leukemia (AML) with translocation t(10;17), and some cases of B-precursor acute lymphoblastic leukemia (pB-ALL). To better understand the function of MSI2 in leukemia, the mRNA targets that are bound and regulated by MSI2 and their MSI2-binding motifs need to be identified.

The homeobox transcription factor HB9 induces senescence and blocks differentiation in hematopoietic stem and progenitor cells.

The homeobox gene encodes for the transcription factor HB9, which is essential for pancreatic as well as motor neuronal development. Beside its physiological expression pattern, aberrant HB9 expression has been observed in several neoplasias. Especially in infant translocation t(7;12) acute myeloid leukemia, aberrant HB9 expression is the only known molecular hallmark and is assumed to be a key factor in leukemic transformation.