Integration of personalised ultrasensitive ctDNA monitoring of patients with metastatic breast cancer to reduce imaging requirements.

Circulating tumour DNA (ctDNA) is an emerging biomarker for monitoring cancers. The personalised disease monitoring in metastatic breast cancer (PDM-MBC) study is an ongoing study instigated to evaluate ctDNA as a biomarker to individualise imaging requirements in patients with MBC. Patients receiving first-line endocrine therapy (aromatase inhibitor + cyclin-dependent kinase 4/6 inhibitor) had plasma samples collected pre-treatment, weeks 2 and 4, and concurrently with imaging until progressive disease (PD).

From Crisis to Complications: A Nationwide Cohort Study Assessing One-Year Cardiovascular and Thromboembolic Risks After Severe COVID-19 Compared to Matched Controls.

The long-term risk of cardiovascular and thrombotic events following severe COVID-19 remains largely unknown. This study aimed to assess the risk of atherosclerotic cardiovascular disease (ASCVD) within one year after hospital discharge in patients who received intensive care for severe COVID-19. A register-based nationwide case-control study on a cohort of patients with severe COVID-19 (cases) requiring mechanical ventilation and discharged alive without experiencing cardiovascular or thrombotic events during their hospital stay.

Personalized circulating tumor DNA analysis for sensitive disease monitoring and detection of relapse in neuroblastoma.

Circulating tumor DNA (ctDNA) has shown potential as a non-invasive tumor biomarker in neuroblastoma. Previous studies used generic assays for detection of selected predefined oncogenic variants as markers of ctDNA, which limits the sensitivity and excludes a subset of patients from analysis. Here we assessed patient-specific ctDNA analysis for treatment evaluation and detection of relapse in neuroblastoma.

Mechanistic basis of atypical TERT promoter mutations.

Non-coding mutations in the TERT promoter (TERTp), typically at one of two bases -124 and -146 bp upstream of the start codon, are among the most prevalent driver mutations in human cancer. Several additional recurrent TERTp mutations have been reported but their functions and origins remain largely unexplained. Here, we show that atypical TERTp mutations arise secondary to canonical TERTp mutations in a two-step process.

Optimal Operation of Cryogenic Calorimeters Through Deep Reinforcement Learning.

Cryogenic phonon detectors with transition-edge sensors achieve the best sensitivity to sub-GeV/c dark matter interactions with nuclei in current direct detection experiments. In such devices, the temperature of the thermometer and the bias current in its readout circuit need careful optimization to achieve optimal detector performance. This task is not trivial and is typically done manually by an expert.

Plasmodial slime moulds (myxomycetes) in Swedish and Nordic folk biology.

Background: Folk biology commonly contains knowledge of many more taxa than those of immediate economic importance. Species with little or no practical use are, however, often overlooked by ethnobiological research. An example are a few Myxomycetes taxa which played an important role in the folk biology and beliefs of pre-industrial Sweden and adjacent Nordic countries, Denmark, Norway and Finland.

From Supernatural to Ornamental: Black Elder ( L., Family Adoxaceae) in Sweden.

Black elder, , is a non-native but now partly naturalized shrub in Sweden; it has been cultivated here at least since the Middle Ages. Previously, this plant was associated with a supernatural being to whom sacrifices were made, and its fruits were used in folk medicine and wood for fuel and crafts. Traditional economic uses vanished with industrialization and urbanization and black elder was mostly planted as an ornamental shrub in urban parks.

Modulation of ABCG2 Transporter Activity by Ko143 Derivatives.

ABCG2 is a multidrug transporter that protects tissues from xenobiotics, affects drug pharmacokinetics, and contributes to multidrug resistance of cancer cells. Here, we present tetracyclic fumitremorgin C analog Ko143 derivatives, evaluate their modulation of purified ABCG2, and report four high-resolution cryo-EM structures and computational analyses to elucidate their interactions with ABCG2. We found that Ko143 derivatives that are based on a ring-opened scaffold no longer inhibit ABCG2-mediated transport activity.

Parental psychopathology and offspring anxiety disorders in childhood and adolescence: A Finnish nationwide register study.

Background: Research suggests an association between parental psychiatric disorders and offspring anxiety disorders, yet comprehensive studies are limited. This study aims to investigate the associations between various parental psychiatric disorders and anxiety disorders in their offspring.

Method: Using Finnish register data, this nested case-control study analyzed 867,175 singleton live births from 1992 to 2006, identifying 21,671 cases of anxiety disorders diagnosed between 1998 and 2016.

Low-dose cryo-electron ptychography of proteins at sub-nanometer resolution.

Cryo-transmission electron microscopy (cryo-EM) of frozen hydrated specimens is an efficient method for the structural analysis of purified biological molecules. However, cryo-EM and cryo-electron tomography are limited by the low signal-to-noise ratio (SNR) of recorded images, making detection of smaller particles challenging. For dose-resilient samples often studied in the physical sciences, electron ptychography - a coherent diffractive imaging technique using 4D scanning transmission electron microscopy (4D-STEM) - has recently demonstrated excellent SNR and resolution down to tens of picometers for thin specimens imaged at room temperature.

CRISPR-Cas target recognition for sensing viral and cancer biomarkers.

Nucleic acid-based diagnostics is a promising venue for detection of pathogens causing infectious diseases and mutations related to cancer. However, this type of diagnostics still faces certain challenges, and there is a need for more robust, simple and cost-effective methods. Clustered regularly interspaced short palindromic repeats (CRISPRs), the adaptive immune systems present in the prokaryotes, has recently been developed for specific detection of nucleic acids.

Long-Lasting Response to Lorlatinib in Patients with ALK-Driven Relapsed or Refractory Neuroblastoma Monitored with Circulating Tumor DNA Analysis.

Unlabelled: Patients with anaplastic lymphoma kinase (ALK)-driven neuroblastoma may respond to tyrosine kinase inhibitors, but resistance to treatment occurs and methods currently used for detection of residual disease have limited sensitivity. Here, we present a national unselected cohort of five patients with relapsed or refractory ALK-driven neuroblastoma treated with lorlatinib as monotherapy and test the potential of targeted circulating tumor DNA (ctDNA) analysis as a guide for treatment decisions in these patients. We developed a sequencing panel for ultrasensitive detection of ALK mutations associated with neuroblastoma or resistance to tyrosine kinase inhibitors and used it for ctDNA analysis in 83 plasma samples collected longitudinally from the four patients who harbored somatic ALK mutations.

Automated fiducial-based alignment of cryo-electron tomography tilt series in Dynamo.

With the advent of modern technologies for cryo-electron tomography (cryo-ET), high-quality tilt series are more rapidly acquired than processed and analyzed. Thus, a robust and fast-automated alignment for batch processing in cryo-ET is needed. While different software packages have made available several approaches for automated marker-based alignment of tilt series, manual user intervention remains necessary for many datasets, thus preventing high-throughput tomography.

Hierarchical Protofilament Intertwining Rules the Formation of Mixed-Curvature Amyloid Polymorphs.

Amyloid polymorphism is a hallmark of almost all amyloid species, yet the mechanisms underlying the formation of amyloid polymorphs and their complex architectures remain elusive. Commonly, two main mesoscopic topologies are found in amyloid polymorphs characterized by non-zero Gaussian and mean curvatures: twisted ribbons and helical fibrils, respectively. Here, a rich heterogeneity of configurations is demonstrated on insulin amyloid fibrils, where protofilament packing can occur, besides the common polymorphs, also in a combined mode forming mixed-curvature polymorphs.

H, C and N backbone resonance assignment of Cel45A from Phanerochaete chrysosporium.

A glycoside hydrolase family 45 (GH45) enzyme from the white-rot basidiomycete fungus Phanerochaete chrysosporium (PcCel45A) was expressed in Pichia pastoris with C and N labelling. A nearly complete assignment of H, C and N backbone resonances was obtained, as well as the secondary structure prediction based on the assigned chemical shifts using the TALOS-N software. The predicted secondary structure was almost identical to previously published crystal structures of the same enzyme, except for differences in the termini of the sequence.

Which leadership style do more narcissistic subordinates prefer in supervisors?

Background And Objective: Subordinates in Western cultures generally prefer supervisors with a democratic rather than autocratic leadership style. It is unclear, however, whether more narcissistic subordinates share or challenge this prodemocratic default attitude. On the one hand, more narcissistic individuals strive for power and thus may favor a democratic supervisor, who grants them power through participation.

Unmet need for mental health care among adolescents in Asia and Europe.

The unmet need for mental health care is a global concern. There is a lack of cross-cultural studies examining adolescent help-seeking behavior from both formal and informal sources, including both high-and lower-income countries. This study investigates mental health help-seeking behavior in eight Asian and European countries.