A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer.

While the effect of amplification-induced oncogene expression in cancer is known, the impact of copy-number gains on "bystander" genes is less understood. We create a comprehensive map of dosage compensation in cancer by integrating expression and copy number profiles from over 8000 tumors in The Cancer Genome Atlas and cell lines from the Cancer Cell Line Encyclopedia. Additionally, we analyze 17 cancer open reading frame screens to identify genes toxic to cancer cells when overexpressed.

Genetic coupling of enhancer activity and connectivity in gene expression control.

Gene enhancers often form long-range contacts with promoters, but it remains unclear if the activity of enhancers and their chromosomal contacts are mediated by the same DNA sequences and recruited factors. Here, we study the effects of expression quantitative trait loci (eQTLs) on enhancer activity and promoter contacts in primary monocytes isolated from 34 male individuals. Using eQTL-Capture Hi-C and a Bayesian approach considering both intra- and inter-individual variation, we initially detect 19 eQTLs associated with enhancer-eGene promoter contacts, most of which also associate with enhancer accessibility and activity.

Acute respiratory tract infections during the first six years of life - results from the German birth cohort study LoewenKIDS.

Objectives: Acute respiratory infections (ARI) often occur in early childhood and are mostly self-limited. However, they impose a high socioeconomic burden and can be associated with chronic diseases later in life. To date, data on self-reported ARI beyond infancy are limited.

A Short Cognitive and Neuropsychiatric Assessment Scale for Progressive Supranuclear Palsy.

Background: Patients with Progressive Supranuclear Palsy (PSP) suffer from several neuropsychological impairments. These mainly affect the frontal lobe and subcortical brain structures. However, a scale for the assessment of cognitive and neuropsychiatric disability in PSP is still missing.

Assessing the Clinical and Functional Status of COPD Patients Using Speech Analysis During and After Exacerbation.

Background: Chronic obstructive pulmonary disease (COPD) affects breathing, speech production, and coughing. We evaluated a machine learning analysis of speech for classifying the disease severity of COPD.

Methods: In this single centre study, non-consecutive COPD patients were prospectively recruited for comparing their speech characteristics during and after an acute COPD exacerbation.

Two-pore channel regulators - Who is in control?

Two-pore channels (TPCs) are adenine nucleotide and phosphoinositide regulated cation channels. NAADP activates and ATP blocks TPCs, while the endolysosomal phosphoinositide PI(3,5)P activates TPCs. TPCs are ubiquitously expressed including expression in the innate as well as the adaptive immune system.

Selection of Early Life Codons by Ultraviolet Light.

How life developed in its earliest stages is a central but notoriously difficult question in science. The earliest lifeforms likely used a reduced set of codon sequences that were progressively completed over time, driven by chemical, physical, and combinatorial constraints. However, despite its importance for prebiotic chemistry, UV radiation has not been considered a selection pressure for the evolution of early codon sequences.

Propensity score matched comparison of lymph node upstaging in early-stage lung cancer: open versus minimally invasive surgery with standardized lymphadenectomy.

Background: Lymph node upstaging represents a quality criterion for standardized lymphadenectomy in lung cancer surgery. The aim of the study was to compare whether the quality of standardized lymphadenectomy in lung cancer surgery is comparable in minimally invasive (video-assisted thoracoscopic surgery) and the open approach (thoracotomy). Furthermore, factors associated with lymph node upstaging were assessed, as was its impact on overall survival and progression-free survival.

Relationship between plasma urea and copeptin in response to arginine stimulation in healthy adults, patients with vasopressin deficiency and primary polydipsia.

Background: Arginine infusion stimulates copeptin secretion, a surrogate marker of arginine vasopressin (AVP), thereby serving as a diagnostic test in the differential diagnosis of suspected AVP deficiency (AVP-D). Yet, the precise mechanism underlying the stimulatory effect of arginine on the vasopressinergic system remains elusive. Arginine plays a significant role in the urea cycle and increases the production of urea.

Lung function-associated exposome profile in the era of climate change: Pooled analysis of 8 population-based European cohorts within the EXPANSE project.

Background: The independent and interrelated long-term effects of the exposome such as air pollution, greenness, and ambient temperature on lung function are not well understood, yet relevant in the light of climate change.

Methods: Pre-bronchodilation FEV1 from five mature birth cohorts (N = 4724) and three adult cohorts (N = 6052) from five European countries were used to assess cross-sectional associations with air pollution, greenness, and ambient temperature, assigned to their residential address. All two-way interactions and square terms were a priori included in building the final elastic net regression model.

Changes in the Microcirculation and Physiologic Perfusion Dynamics of Free DIEP Flaps in the First 72 h After Breast Reconstruction.

The autologous reconstruction of the female breast using a microsurgical DIEP flap is a reliable and safe method. To detect impairments early and preserve the microvascular flap through timely revision, a better understanding of physiologic perfusion dynamics is necessary. This exploratory study examines changes in microcirculation in free DIEP flaps within the first 72 h after vascular anastomosis using laser Doppler flowmetry and white-light spectrophotometry.

Prepartum Vaccination Against Neonatal Calf Diarrhea and Its Effect on Mammary Health and Milk Yield of Dairy Cows: A Retrospective Study Addressing Non-Specific Effects of Vaccination.

Prepartum vaccinations against neonatal calf diarrhea pathogens are administered in late pregnancy to provide passive immunity to calves through protective colostral antibodies. Potential non-specific effects of the vaccine on maternal innate immune responses and disease susceptibility during the sensitive transition period have not been addressed so far. In this retrospective study, data from 73,378 dairy cows on 20 farms in Germany were analyzed, using linear mixed-effects regression, quantile regression, and decision-tree-algorithms, to investigate the effects of prepartum vaccination on mammary health and milk yield by comparing non-vaccinated and vaccinated transition periods.

Protective effects of neutrophil serine protease inhibition against ischemia-reperfusion injury in lung or heart transplantation.

Transplanted organs are inevitably exposed to ischemia-reperfusion (IR) injury, which is known to cause graft dysfunction. Functional and structural changes that follow IR tissue injury are mediated by neutrophils through the production of oxygen-derived free radicals, as well as from degranulation which entails the release of proteases and other pro-inflammatory mediators. Neutrophil serine proteases (NSPs) are believed to be the principal triggers of post-ischemic reperfusion damage.

ATM Expression and Activation in Ataxia Telangiectasia Patients with and without Class Switch Recombination Defects.

Background: Ataxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.

RNase T2 restricts TLR13-mediated autoinflammation in vivo.

RNA-sensing TLRs are strategically positioned in the endolysosome to detect incoming nonself RNA. RNase T2 plays a critical role in processing long, structured RNA into short oligoribonucleotides that engage TLR7 or TLR8. In addition to its positive regulatory role, RNase T2 also restricts RNA recognition through unknown mechanisms, as patients deficient in RNase T2 suffer from neuroinflammation.

Addition by Subtraction: Reversing Epikeratophakia and Stromal Scarring in a Patient With Myopia Magna.

Purpose: To describe a three-phase surgical approach for managing progressive visual decline in a patient with myopia magna and a history of epikeratophakia.

Methods: A 55-year-old woman with previous epikeratophakia surgery in both eyes experienced progressive visual deterioration. The three-phase approach included: (1) removal of the epikeratophakia lenticule, (2) cataract extraction with intraocular lens implantation, and (3) transepithelial topography-guided photorefractive keratectomy (trans-PRK).

Simplified Outcome Prediction in Patients Undergoing Transcatheter Tricuspid Valve Intervention by Survival Tree-Based Modelling.

Background: Patients with severe tricuspid regurgitation (TR) typically present with heterogeneity in the extent of cardiac dysfunction and extra-cardiac comorbidities, which play a decisive role for survival after transcatheter tricuspid valve intervention (TTVI).

Objectives: This aim of this study was to create a survival tree-based model to determine the cardiac and extra-cardiac features associated with 2-year survival after TTVI.

Methods: The study included 918 patients (derivation set, n = 631; validation set, n = 287) undergoing TTVI for severe TR.

A single gene orchestrates androgen variation underlying male mating morphs in ruffs.

Androgens are pleiotropic and play pivotal roles in the formation and variation of sexual phenotypes. We show that differences in circulating androgens between the three male mating morphs in ruff sandpipers are linked to 17-beta hydroxysteroid dehydrogenase 2 (HSD17B2), encoded by a gene within the supergene that determines the morphs. Low-testosterone males had higher expression in blood than high-testosterone males, as well as in brain areas related to social behaviors and testosterone production.

Persistent symptoms and clinical findings in adults with post-acute sequelae of COVID-19/post-COVID-19 syndrome in the second year after acute infection: A population-based, nested case-control study.

Background: Self-reported health problems following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are common and often include relatively non-specific complaints such as fatigue, exertional dyspnoea, concentration or memory disturbance and sleep problems. The long-term prognosis of such post-acute sequelae of COVID-19/post-COVID-19 syndrome (PCS) is unknown, and data finding and correlating organ dysfunction and pathology with self-reported symptoms in patients with non-recovery from PCS is scarce. We wanted to describe clinical characteristics and diagnostic findings among patients with PCS persisting for >1 year and assessed risk factors for PCS persistence versus improvement.

Centriolar cap proteins CP110 and CPAP control slow elongation of microtubule plus ends.

Centrioles are microtubule-based organelles required for the formation of centrosomes and cilia. Centriolar microtubules, unlike their cytosolic counterparts, are stable and grow very slowly, but the underlying mechanisms are poorly understood. Here, we reconstituted in vitro the interplay between the proteins that cap distal centriole ends and control their elongation: CP110, CEP97, and CPAP/SAS-4.

Stay Connected to Be Diverse!

Plankton biodiversity is crucial for the functioning of aquatic ecosystems, influencing nutrient cycling, food web dynamics, and carbon storage. Global change and habitat destruction disrupt these ecosystems, reducing species diversity and ecosystem resilience. Connectivity between aquatic habitats supports biodiversity by enabling species migration, genetic diversity, and recovery from disturbances.

Does the habitual dietary intake of adults in Bavaria, Germany, match dietary intake recommendations? Results of the 3rd Bavarian Food Consumption Survey.

Objective: Monitoring dietary habits is crucial for identifying shortcomings and delineating countermeasures. About 20 years after the last population-based surveys in Bavaria and Germany, dietary habits were assessed to describe the intake distributions and compare these with recommendations at food and nutrient level.

Methods: The 3rd Bavarian Food Consumption Survey (BVS III) was designed as a diet survey representative of adults in Bavaria; from 2021 to 2023, repeated 24-h diet recalls were collected by telephone using the software GloboDiet©.

Direct and indirect effects of land use on microbiomes of trap-nesting solitary bee larvae and nests.

Introduction: The global decline in biodiversity and insect populations highlights the urgent need to conserve ecosystem functions, such as plant pollination by solitary bees. Human activities, particularly agricultural intensification, pose significant threats to these essential services. Changes in land use alter resource and nest site availability, pesticide exposure and other factors impacting the richness, diversity, and health of solitary bee species.

Influence of sintering temperature and aging on the color and translucency of zirconia.

Statement Of Problem: Translucent zirconias are promising materials for monolithic prostheses. However, information on their optical behavior after sintering and aging protocols is scarce.

Purpose: The purpose of this in vitro study was to evaluate the color and translucency of zirconia subjected to different sintering temperatures and aging.