Holmbergfanning0954

Cetuximab, an EGFR inhibitor used to treat multiple cancer types, including colon cancer, causes severe skin toxicity in 5%-20% of patients, leading to decreased quality of life and treatment delays. click here Our understanding of which patients have an increased risk of severe toxicities is limited. We conducted a genome-wide association study to identify germline variants predictive of cetuximab-induced severe skin toxicity.

Our study included 1,209 patients with stage III colon cancer randomized to receive cetuximab plus 5-fluorouracil and oxaliplatin as part of the NCCTG N0147 (Alliance) clinical trial. Skin toxicity outcomes were collected using the Common Toxicity Criteria for Adverse Events version 3.0. We performed genotyping, evaluating approximately 10 million genetic variants. We used logistic regression to evaluate the association of each genetic variant and severe (grade ≥ 3) skin toxicity, adjusting for age, sex, and genetic ancestry. Genome-wide significance was defined as

< 5 × 10

.

Participants were predominantly middle-aged white men; 20% (

= 243) experienced severe skin toxicity. Two genetic variants in the retinoic acid receptor alpha (

) gene were significantly associated with severe skin toxicity [OR, 3.93; 95% confidence interval (CI), 2.47-6.25;

< 7.8 × 10

]. Functional annotations indicate these variants are in the

promoter. Additional significantly associated variants were identified in chromosome 2 intergenic regions.

Identified variants could represent a potential target for risk stratification of patients with colon cancer receiving cetuximab.

Retinoids have shown promise in the treatment of cetuximab-induced skin toxicity, so follow-up work could evaluate whether individuals with the

variant would benefit from retinoid therapy.

Retinoids have shown promise in the treatment of cetuximab-induced skin toxicity, so follow-up work could evaluate whether individuals with the RARA variant would benefit from retinoid therapy.How the diverse bacterial communities inhabiting desert soils maintain energy and carbon needs is much debated. Traditionally, most bacteria are thought to persist by using organic carbon synthesized by photoautotrophs following transient hydration events. Recent studies focused on Antarctic desert soils have revealed, however, that some bacteria use atmospheric trace gases, such as hydrogen (H2), to conserve energy and fix carbon independently of photosynthesis. In this study, we investigated whether atmospheric H2 oxidation occurs in four nonpolar desert soils and compared this process to photosynthesis. To do so, we first profiled the distribution, expression, and activities of hydrogenases and photosystems in surface soils collected from the South Australian desert over a simulated hydration-desiccation cycle. Hydrogenase-encoding sequences were abundant in the metagenomes and metatranscriptomes and were detected in actinobacterial, acidobacterial, and cyanobacterial metagenome-assembled genomes. Native dn this work, we reveal that atmospheric hydrogen serves as a major previously overlooked energy source for a large proportion of desert bacteria. We show that both chemoheterotrophic and photoautotrophic bacteria have the potential to oxidize hydrogen across deserts sampled across four continents. Whereas hydrogen oxidation was slow in native dry deserts, it increased by three orders of magnitude together with photosynthesis following hydration. This study revealed that continual harvesting of atmospheric energy sources may be a major way that desert communities adapt to long periods of water and energy deprivation, with significant ecological and biogeochemical ramifications.Acinetobacter baumannii has been reported as a multidrug-resistant bacterium due to biofilms and antimicrobial resistance mechanisms. Hence, novel therapeutic strategies are necessary to overcome A. baumannii infections. This study revealed that citral at 200 μg/ml attenuated A. baumannii biofilms by up to 90% without affecting viability. Furthermore, microscopic analyses and in vitro assays confirmed the antibiofilm efficacy of citral. The global effect of citral on A. baumannii was evaluated by proteomic, transcriptional, and in silico approaches. Two-dimensional (2D) gel electrophoresis and matrix-assisted laser desorption ionization-time of flight/time of flight (MALDI-TOF/TOF) analyses were used to assess the effect of citral on the A. baumannii cellular proteome. Quantitative real-time PCR (qPCR) analysis was done to validate the proteomic data and identify the differentially expressed A. baumannii genes. Protein-protein interactions, gene enrichment, and comparative gene network analyses were performedol A. baumannii biofilm-associated issues. The present study demonstrated the strong antibiofilm and antivirulence efficacy of citral against A. baumannii In addition, proteomic analysis revealed the multitarget potential of citral against A. baumannii Furthermore, citral treatment enhances the susceptibility of A. baumannii to the host innate immune system and reactive oxygen species (ROS). Cytotoxicity analysis revealed the nonfatal effect of citral on human PBMCs. Therefore, citral could be the safest therapeutic compound and can be taken for further clinical evaluation for the treatment of biofilm-associated infections by A. baumannii.Here, we report three new Acidiphilium genomes, reclassified existing Acidiphilium species, and performed the first comparative genomic analysis on Acidiphilium in an attempt to address the metabolic potential, ecological functions, and evolutionary history of the genus Acidiphilium In the genomes of Acidiphilium, we found an abundant repertoire of horizontally transferred genes (HTGs) contributing to environmental adaption and metabolic expansion, including genes conferring photosynthesis (puf, puh), CO2 assimilation (rbc), capacity for methane metabolism (mmo, mdh, frm), nitrogen source utilization (nar, cyn, hmp), sulfur compound utilization (sox, psr, sqr), and multiple metal and osmotic stress resistance capacities (czc, cop, ect). Additionally, the predicted donors of horizontal gene transfer were present in a cooccurrence network of Acidiphilium Genome-scale positive selection analysis revealed that 15 genes contained adaptive mutations, most of which were multifunctional and played critical roles in ticated by phylogenetic reconstruction and gene context comparison. This study has advanced our understanding of microbial evolution and biogeochemical cycling in extreme niches.Colonization resistance, i.e., the protective effects of associated microbiota for the animal host against pathogen infection, has been studied widely over the last 100 years. However, few molecules mediating colonization resistance have been identified. In the symbiosis formed by Delia antiqua and its associated microbes, six bacteria protect larvae from infection with the entomopathogen Beauveria bassiana, providing an ideal model to investigate the chemical mechanism for colonization resistance. Subsequently using this symbiotic system, we first compared effects of the six bacterial species, and one control bacterium (Klebsiella oxytoca) that showed no antifungal effects, on B. bassiana and its infection of D. antiqua Second, metabolomic profiles of the six bacteria and K. link2 oxytoca were compared to identify candidate metabolites that may prevent infection. link3 Third, the concentrations of candidate metabolites in situ from axenic and nonaxenic larvae were determined. Finally, effects of artificial metabolite coy microbes that protect the insect and microbes that cannot protect the insect, the question of how the microbes protect the insect is answered. It turns out that body surface bacteria produce a metabolite cocktail that inhibits colonization of B.bassiana and consequently protects the insect. This work reveals novel molecules with antifungal activity, which may aid in discovery and expansion of new prophylactic and therapeutic natural chemicals for treating infectious diseases.Magnetotactic bacteria (MTB) stand out by their ability to manufacture membrane-enclosed magnetic organelles, so-called magnetosomes. Previously, it has been assumed that a genomic region of approximately 100 kbp, the magnetosome island (MAI), harbors all genetic determinants required for this intricate biosynthesis process. Recent evidence, however, argues for the involvement of additional auxiliary genes that have not been identified yet. In the present study, we set out to delineate the full gene complement required for magnetosome production in the alphaproteobacterium Magnetospirillum gryphiswaldense using a systematic genome-wide transposon mutagenesis approach. By an optimized procedure, a Tn5 insertion library of 80,000 clones was generated and screened, yielding close to 200 insertants with mild to severe impairment of magnetosome biosynthesis. Approximately 50% of all Tn5 insertion sites mapped within the MAI, mostly leading to a nonmagnetic phenotype. In contrast, in the majority of weakly magneticas been mainly gathered using reverse genetics and candidate approaches. In contrast, nontargeted forward genetics studies are lacking, since application of such techniques in MTB has been complicated for a number of technical reasons. Here, we report on the first comprehensive transposon mutagenesis study in MTB, aiming at systematic identification of auxiliary genes necessary to support magnetosome formation in addition to key genes harbored in the magnetosome island (MAI). Our work considerably extends the candidate set of novel subsidiary determinants and shows that the full gene complement underlying magnetosome biosynthesis is larger than assumed. In particular, we were able to define certain cellular pathways as specifically important for magnetosome formation that have not been implicated in this process so far.

Mobile phone video call applications generally did not undergo testing in randomised controlled clinical trials prior to their implementation in patient care regarding the rate of successful patient visits and impact on the physician-patient relationship.

The National Center for Tumour Diseases (NCT) MOBILE trial was a monocentric open-label randomised controlled clinical trial of patients with solid tumours undergoing systemic cancer therapy with need of a follow-up visit with their consulting physician at outpatient clinics. 66 patients were 11 randomised to receive either a standard in-person follow-up visit at outpatient clinics or a video call via a mobile phone application. The primary outcome was feasibility defined as the proportion of patients successfully completing the first follow-up visit. Secondary outcomes included success rate of further video calls, time spent by patient and physician, patient satisfaction and quality of physician-patient relationship.

Success rate of the first follow-u88.

DRKS00015788.Political and environmental factors-e.g., regional conflicts and global warming-increase large-scale migrations, posing extraordinary societal challenges to policymakers of destination countries. A common concern is that such a massive arrival of people-often from a country with a disrupted healthcare system-can increase the risk of vaccine-preventable disease outbreaks like measles. We analyze human flows of 3.5 million (M) Syrian refugees in Turkey inferred from massive mobile-phone data to verify this concern. We use multilayer modeling of interdependent social and epidemic dynamics to demonstrate that the risk of disease reemergence in Turkey, the main host country, can be dramatically reduced by 75 to 90% when the mixing of Turkish and Syrian populations is high. Our results suggest that maximizing the dispersal of refugees in the recipient population contributes to impede the spread of sustained measles epidemics, rather than favoring it. Targeted vaccination campaigns and policies enhancing social integration of refugees are the most effective strategies to reduce epidemic risks for all citizens.