App-based assessment of patient-reported outcomes in the Molecular Tumor Board in the Center for Personalized Medicine-(TRACE).

Background: Biomarker-based therapies are increasingly used in cancer patients outside clinical trials. Systematic assessment of patient-reported outcomes (PRO) is warranted to take patients' perspectives during biomarker-based therapies into consideration. We assessed the feasibility of an electronic PRO assessment via a smartphone application.

Glacial vicariance and secondary contact shape demographic histories in a freshwater mussel species complex.

Characterizing the mechanisms influencing the distribution of genetic variation in aquatic species can be difficult due to the dynamic nature of hydrological landscapes. In North America's Central Highlands, a complex history of glacial dynamics, long-term isolation, and secondary contact have shaped genetic variation in aquatic species. Although the effects of glacial history have been demonstrated in many taxa, responses are often lineage- or species-specific and driven by organismal ecology.

Discovery and overproduction of novel highly bioactive pamamycins through transcriptional engineering of the biosynthetic gene cluster.

Background: Pamamycins are a family of highly bioactive macrodiolide polyketides produced by Streptomyces alboniger as a complex mixture of derivatives with molecular weights ranging from 579 to 705 Daltons. The large derivatives are produced as a minor fraction, which has prevented their isolation and thus studies of chemical and biological properties.

Results: Herein, we describe the transcriptional engineering of the pamamycin biosynthetic gene cluster (pam BGC), which resulted in the shift in production profile toward high molecular weight derivatives.

Holistic rockfall risk assessment in high mountain areas affected by seismic activity: Application to the Uspallata valley, Central Andes, Chile.

Over large regions exposed to natural disasters, cascading effects resulting from complex or concatenated natural processes may represent a large portion of total risk. Populated high-mountain environments are a major concern, and methods for large-scale quantitative risk analyses are urgently required to improve risk mitigation. This article presents a comprehensive quantitative rockfall risk assessment over a large archetypal valley of the Andean mountains, in Central Chile, which integrates a wide spectrum of elements at risk.

An investigation of neurological and/or biomechanical factors underpinning the effect of a thrust manipulation on chronic ankle symptoms: an observational study.

Background: Ankle sprains are a commonly occurring musculoskeletal injury potentially resulting in persistent pain and/or altered motion. Thrust manipulation may serve as an interventional strategy but limited evidence exists on the mechanism(s) by which a change to symptoms might occur.

Objective: The study sought to quantify the immediate effect of a thrust manipulation to the ankle to determine a mechanism by which change to symptoms occurred.

Parent-child separation and cardiometabolic outcomes and risk factors in adulthood: A systematic review.

Background: Parent-child separation has been associated with negative mental health across childhood and adulthood, yet little is known about the long-term impacts for cardiovascular health. This systematic review synthesized and evaluated the quality of the literature examining the association between exposures to parent-child separation and cardiometabolic outcomes in adulthood.

Methods: Following a registered protocol, online databases (Pubmed, PsycInfo, and Web of Science) were searched for relevant studies.

Sustainable Development Goals and risks: The Yin and the Yang of the paths towards sustainability.

The United Nations 2030 Agenda and Sustainable Development Goals (SDGs) define a path towards a sustainable future, but given that uncertainty characterises the outcomes of any SDG-related actions, risks in the implementation of the Agenda need to be addressed. At the same time, most risk assessments are narrowed to sectoral approaches and do not refer to SDGs. Here, on the basis of a literature review and workshops, it is analysed how SDGs and risks relate to each other's in different communities.

Towards a holistic paradigm for long-term snow avalanche risk assessment and mitigation.

In mountain territories, snow avalanches are a prevalent threat. Long-term risk management involves defining meaningful compromises between protection and overall sustainability of communities and their environment. Methods able to (i) consider all sources of losses, (ii) account for the high uncertainty levels that affect all components of the risk and (iii) cope for marked non-stationarities should be employed.

Assuming accuracy, pretending influence? Risks of measuring, monitoring and reporting sustainable development goals.

From the local to global level, indicators and reports are produced and published to support the transition towards sustainable development. Building from two European-level science-policy workshops, this perspective essay discusses the types of risks involved with such sustainability reporting. The analysis is rooted in the framework of the UN 2030 Agenda and sustainable development goals (SDG).

Modulation of Motor Evoked Potentials via the Cutaneous Silent Period within Proximal-Distal Muscles in the Upper-Limb.

A single pulse of high intensity electrical current delivered to the digits of the hand during voluntary contractions produces a period of decreased electromyographic (EMG) activity, known as a cutaneous silent period (CSP) (Caccia and Violini, 1973; Inghilleri et al., 1997; Uncini et al., 1991).

Upslope migration of snow avalanches in a warming climate.

Snow is highly sensitive to atmospheric warming. However, because of the lack of sufficiently long snow avalanche time series and statistical techniques capable of accounting for the numerous biases inherent to sparse and incomplete avalanche records, the evolution of process activity in a warming climate remains little known. Filling this gap requires innovative approaches that put avalanche activity into a long-term context.

Educational mobility and telomere length in middle-aged and older adults: testing three alternative hypotheses.

Critical period, social mobility, and social accumulation are three hypotheses that may explain how educational mobility impacts health. Thus far, there is little evidence on how these processes are associated with biological aging as measured by telomere length. Using cross-sectional data from the 2008 Health and Retirement Study, we examined the association between educational mobility (parental education and contemporaneous education) and telomere length.

Cyclofaulknamycin with the Rare Amino Acid D-capreomycidine Isolated from a Well-Characterized Strain.

Targeted genome mining is an efficient method of biosynthetic gene cluster prioritization within constantly growing genome databases. Using two capreomycidine biosynthesis genes, alpha-ketoglutarate-dependent arginine beta-hydroxylase and pyridoxal-phosphate-dependent aminotransferase, we identified two types of clusters: one type containing both genes involved in the biosynthesis of the abovementioned moiety, and other clusters including only arginine hydroxylase. Detailed analysis of one of the clusters, the cluster from , led to the identification of a cyclic peptide that contains a rare D-capreomycidine moiety for the first time.

Stressful Life Events and Obesity in the United States: The Role of Nativity and Length of Residence.

Purpose: Obesity is a public health issue in the United States (US), that disproportionately affects marginalized group members. Stressful life events (SLE) have been implicated as an obesogenic risk factor. However, there is scant research examining of the role of nativity status and length of residence in the relationship between SLE and obesity.

Effects of controlled ovarian stimulation on vascular barrier and endothelial glycocalyx: a pilot study.

Purpose: Controlled ovarian stimulation significantly amplifies the number of maturing and ovulated follicles as well as ovarian steroid production. The ovarian hyperstimulation syndrome (OHSS) increases capillary permeability and fluid extravasation. Vascular integrity intensely is regulated by an endothelial glycocalyx (EGX) and we have shown that ovulatory cycles are associated with shedding of EGX components.

Efficient IL-2R signaling differentially affects the stability, function, and composition of the regulatory T-cell pool.

Signaling via interleukin-2 receptor (IL-2R) is a requisite for regulatory T (Treg) cell identity and function. However, it is not completely understood to what degree IL-2R signaling is required for Treg cell homeostasis, lineage stability and function in both resting and inflammatory conditions. Here, we characterized a spontaneous mutant mouse strain endowed with a hypomorphic Tyr129His variant of CD25, the α-chain of IL-2R, which resulted in diminished receptor expression and reduced IL-2R signaling.

Efficient homing of T cells via afferent lymphatics requires mechanical arrest and integrin-supported chemokine guidance.

Little is known regarding lymph node (LN)-homing of immune cells via afferent lymphatics. Here, we show, using a photo-convertible Dendra-2 reporter, that recently activated CD4 T cells enter downstream LNs via afferent lymphatics at high frequencies. Intra-lymphatic immune cell transfer and live imaging data further show that activated T cells come to an instantaneous arrest mediated passively by the mechanical 3D-sieve barrier of the LN subcapsular sinus (SCS).

Author Correction: Global glacier mass changes and their contributions to sea-level rise from 1961 to 2016.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

B cell hyperactivation in an Ackr4-deficient mouse strain is not caused by lack of ACKR4 expression.

The majority of genetically modified C57BL/6 mice contain congenic passenger DNA around the targeted gene locus as they were generated from 129-derived embryonic stem cells (ESCs) with subsequent backcrossing to the C57BL/6 genetic background. When studying the role of atypical chemokine receptor 4 (ACKR4) in the immune system, we realized that the two available Ackr4-deficient mouse strains (Ackr4 and Ackr4 ) show profoundly different phenotypes: Compared to wild-type and Ackr4 mice, Ackr4 mice show a strong accumulation of plasma blasts in mesenteric lymph node and spleen as well as increased B cell proliferation after in vitro activation. This phenotype was maintained after further backcrossing to C57BL/6 mice and was even present in heterozygous Ackr4 animals, suggesting that a gene variant on the targeted chromosome might cause this phenotype.

Approaching measles elimination in Switzerland: changing epidemiology 2007-2018.

Switzerland is aiming to eliminate measles, in line with the objectives of the World Health Organization (WHO). Physicians, laboratories and public health authorities have made great efforts to reach this goal. A continually increasing measles vaccination coverage and other preventive measures have made an impact: no major measles outbreak has been recorded since 2011.

Tree-ring reconstruction of snow avalanche activity: Does avalanche path selection matter?

In the current context of anthropogenic global warming, one of the purposes of dendrogeomorphic analyses is to provide long and continuous chronologies of mass movements, so as to detect potential trends or shift related to increasing temperatures. However, on documented slopes, the comparison between historical archives and tree-ring records suggests that dendrogeomorphic reconstructions systematically underestimate the natural activity of the process under investigation. In the specific case of snow avalanches, underestimation generally amounts to 50% and the main causes generally given for this difference are related to the magnitude of past events.

Climate controls on snow reliability in French Alps ski resorts.

Ski tourism is a major sector of mountain regions economy, which is under the threat of long-term climate change. Snow management, and in particular grooming and artificial snowmaking, has become a routine component of ski resort operations, holding potential for counteracting the detrimental effect of natural snow decline. However, conventional snowmaking can only operate under specific meteorological conditions.

Chemokines and other mediators in the development and functional organization of lymph nodes.

Secondary lymphoid organs like lymph nodes (LNs) are the main inductive sites for adaptive immune responses. Lymphocytes are constantly entering LNs, scanning the environment for their cognate antigen and get replenished by incoming cells after a certain period of time. As only a minor percentage of lymphocytes recognizes cognate antigen, this mechanism of permanent recirculation ensures fast and effective immune responses when necessary.