The Asymptomatic Proportion of SARS-CoV-2 Omicron Variant Infections in Households: A Systematic Review.

Understanding the clinical spectrum of SARS-CoV-2 infection, including the asymptomatic fraction, is important as asymptomatic individuals are still able to infect other individuals and contribute to ongoing transmission. The WHO Unity Household transmission investigation (HHTI) protocol provides a platform for the prospective and systematic collection of high-quality clinical, epidemiological, serological and virological data from SARS-CoV-2 confirmed cases and their household contacts. These data can be used to understand key severity and transmissibility parameters-including the asymptomatic proportion-in relation to local epidemic context and help inform public health response. We aimed to estimate the asymptomatic proportion of SARS-CoV-2 Omicron variant infections in Unity-aligned HHTIs. We conducted a systematic review and meta-analysis in alignment with the PRISMA 2020 guidelines and registered our systematic review on PROSPERO (CRD42022378648). We searched EMBASE, Web of Science, MEDLINE and bioRxiv and medRxiv from 1 November 2021 to 22 August 2023. We identified 8368 records, of which 98 underwent full text review. We identified only three studies for data extraction, with substantial variation in study design and corresponding estimates of the asymptomatic proportion. As a result, we did not generate a pooled estimate or I2 metric. The limited number of quality studies that we identified highlights the need for improved preparedness and response capabilities to facilitate robust HHTI implementation, analysis and reporting, to better inform national, regional and global risk assessments and policymaking.

The interaction of size-selected Ru3 clusters with TiO2: depth-profiling of encapsulated clusters.

Ru is a metal of interest in catalysis. Monodisperse Ru3 clusters as catalytic sites are relevant for the development of catalysts because clusters use significantly lower amounts of precious materials for forming active sites due to the small size of the cluster. However, retaining the mono-dispersity of the cluster size after deposition is a challenge because surface energy could drive both agglomeration and encapsulation of the clusters. In the present work Ru3 clusters are deposited by chemical vapor deposition (CVD) of Ru3(CO)12 and cluster source depositions of bare Ru3 onto radio frequency sputter-deposited TiO2 (RF-TiO2) substrates, TiO2(100), and SiO2. When supported on RF-TiO2, bare Ru3 is encapsulated by a layer of titania substrate material during deposition with a cluster source. Ligated Ru3(CO)12 is also encapsulated by a layer of titania when deposited onto sputter-treated RF-TiO2, but only through heat treatment which is required to remove most of the ligands. The titania overlayer thickness was determined to be 1-2 monolayers for Ru3(CO)12 clusters on RF-TiO2, which is thin enough for catalytic or photocatalytic reactions to potentially occur even without clusters being part of the very outermost layer. The implication for catalysis of the encapsulation of Ru3 into the RF-TiO2 is discussed. Temperature-dependent X-ray photoelectron spectroscopy (XPS), angle-resolved XPS, and temperature-dependent low energy ion scattering (TD-LEIS) are used to probe how the cluster-surface interaction changes due to heat treatment and scanning transmission electron microscopy (STEM) was used to image the depth of the surface from side-on.

Reducing the lipase LIPE in mutant α-synuclein mice improves Parkinson-like deficits and reveals sex differences in fatty acid metabolism.

Impaired lipid metabolism is a risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB) and can shift the physiological α-synuclein (αS) tetramer-monomer (T:M) ratio toward aggregation prone monomers. A resultant increase in phospho-serine 129+ αS monomers associating with excess mono- and polyunsaturated fatty acids contributes to the αS aggregation. We previously reported that decreasing the release of monounsaturated fatty acids (MUFAs) by reducing or inhibiting the hormone sensitive lipase (LIPE) reversed pathologic αS phosphorylation and improved soluble αS homeostasis in cultured αS triplication PD neurons and reduced DAergic neurodegeneration in a C.elegans αS model. However, assessing LIPE as a potential therapeutic target for progressive PD motor phenotypes has not been investigated. 3 K αS mice, representing a biochemical and neuropathological amplification of the E46K fPD-causing mutation, have decreased αS T:M ratios, lipidic aggregates, and a L-DOPA responsive PD-like motor syndrome. Here, we reduced LIPE by crossings of 3 K mice with LIPE null mice, which attenuated motor deficits in male LIPE+/- knockdown (LKD)-3 K mice. Heterozygous LIPE reduction was associated with an improved αS T:M ratio, and dopaminergic neurotransmitter levels and fiber densities. In female 3 K-LKD mice, an increase in pS129+ and larger lipid droplets (LDs) likely decreased the benefits seen in males. Reducing LIPE decreased MUFA release from neutral lipid storage, thereby reducing MUFA in phospholipid membranes with which αS interacts. Our study highlights fatty acid turnover as a therapeutic target for Lewy body diseases and support LIPE as a promising target in males. LIPE regulation represents a novel approach to mitigate PD and DLB risk and treat disease.

Efficiency droop in zincblende InGaN/GaN quantum wells.

The decrease in emission efficiency with increasing drive current density, known as 'droop', of c-plane wurtzite InGaN/GaN quantum wells presently limits the use of light-emitting diodes based on them for high brightness lighting applications. InGaN/GaN quantum wells grown in the alternative zincblende phase are free of the strong polarisation fields that exacerbate droop and so were investigated by excitation-dependent photoluminescence and photoreflectance studies. Polarisation-resolved measurements revealed that for all excitation densities studied the emission from such samples largely originates from similar microstructures or combinations of microstructures that form within the quantum well layers. Emission efficiency varies significantly with excitation at 10 K showing that non-radiative recombination processes are important even at low temperature. The onset of efficiency droop, as determined by photomodulated reflection measurements, occurred at a carrier density of around 1.2 × 1020 cm-3 - an order of magnitude greater than the value reported for a reference wurtzite quantum well sample using the same method. The high carrier density droop onset combined with the much shorter carrier lifetime within zincblende InGaN/GaN quantum wells indicate they have the potential to effectively delay efficiency droop when used in GaN based light-emitting diodes. However, the material quality of the quantum well layers need to be improved by preventing the formation of microstructures within these layers, and the importance of the role played by non-radiative centres in the QW layer needs to be elucidated, to fully realise the material's potential.

Multi-centric evaluation of Truenat MTB and MTB-RIF Dx assays for diagnosis of extrapulmonary tuberculosis.

Extra-pulmonary TB (EPTB) is difficult to diagnose due to paucibacillary nature of disease. Current study evaluated accuracy of Truenat MTB and MTB-Rif Dx (TN), for detection of Mycobacterium tuberculosis and resistance to rifampicin. Samples were collected from 2103 treatment naive adults with presumptive EPTB, and tested by smear microscopy, liquid culture (LC) (MGIT-960) and GeneXpert MTB/RIF (GX) (Microbiological Reference Standards, MRS). TN results were compared to MRS and Composite Reference Standards (CRS, Microbiology, histopathology, radiology, clinical features prompting decision to treat, response to treatment). CRS grouped patients into 551 confirmed, 1096 unconfirmed, and 409 as unlikely TB. TN sensitivity and specificity was 73.7% and 90.4% against GX. Against LC, Overall sensitivity of GX was 67.6%, while that of TN was 62.3%. Highest sensitivity by TN was observed in pus samples (89%) and highest specificity (92%) in CSF samples, similar to GX. TN sensitivity was better in fluid and biopsy samples and slightly inferior for lymph node aspirates compared to GX. TN sensitivity for RIF resistance detection was slightly superior to GX. TN and GX results were further compared to Clinical Reference Standards. TN detected 170 TB patients initiated on treatment missed by GX, while GX detected 113 such patients missed by TN. Of 124 samples with RIF resistance discordance between GX and TN, GX reported 103/124 as sensitive, 3/124 as indeterminate and 18 as resistant (13/18 samples had low/very low DNA load) while TN reported RIF resistance indeterminate in 103/111 low/very low DNA load samples. Due to paucibacillary nature of EPTB samples, culture yield was poor and phenotypic drug susceptibility testing failed to resolve the discordance. The study establishes TN at par with GX and can be utilized for quick and accurate diagnosis of EPTB.

Strong doping reduction on wafer-scale CVD graphene devices via Al2O3ALD encapsulation.

We present the electrical characterization of wafer-scale graphene devices fabricated with an industrially-relevant, contact-first integration scheme combined with Al2O3encapsulation via atomic layer deposition. All the devices show a statistically significant reduction in the Dirac point position,Vcnp, from around +47 V to between -5 and 5 V (on 285 nm SiO2), while maintaining the mobility values. The data and methods presented are relevant for further integration of graphene devices, specifically sensors, at the back-end-of-line of a standard CMOS flow.

A catalogue of recombination coldspots in interspecific tomato hybrids.

Increasing natural resistance and resilience in plants is key for ensuring food security within a changing climate. Breeders improve these traits by crossing cultivars with their wild relatives and introgressing specific alleles through meiotic recombination. However, some genomic regions are devoid of recombination especially in crosses between divergent genomes, limiting the combinations of desirable alleles. Here, we used pooled-pollen sequencing to build a map of recombinant and non-recombinant regions between tomato and five wild relatives commonly used for introgressive tomato breeding. We detected hybrid-specific recombination coldspots that underscore the role of structural variations in modifying recombination patterns and maintaining genetic linkage in interspecific crosses. Crossover regions and coldspots show strong association with specific TE superfamilies exhibiting differentially accessible chromatin between somatic and meiotic cells. About two-thirds of the genome are conserved coldspots, located mostly in the pericentromeres and enriched with retrotransposons. The coldspots also harbor genes associated with agronomic traits and stress resistance, revealing undesired consequences of linkage drag and possible barriers to breeding. We presented examples of linkage drag that can potentially be resolved by pairing tomato with other wild species. Overall, this catalogue will help breeders better understand crossover localization and make informed decisions on generating new tomato varieties.

Diagnostic accuracy of lung ultrasound in diagnosis of ARDS and identification of focal or non-focal ARDS subphenotypes: a systematic review and meta-analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory condition with high mortality rates, accounting for 10% of all intensive care unit admissions. Lung ultrasound (LUS) as diagnostic tool for acute respiratory failure has garnered widespread recognition and was recently incorporated into the updated definitions of ARDS. This raised the hypothesis that LUS is a reliable method for diagnosing ARDS. OBJECTIVES: We aimed to establish the accuracy of LUS for ARDS diagnosis and classification of focal versus non-focal ARDS subphenotypes. METHODS: This systematic review and meta-analysis used a systematic search strategy, which was applied to PubMed, EMBASE and cochrane databases. Studies investigating the diagnostic accuracy of LUS compared to thoracic CT or chest radiography (CXR) in ARDS diagnosis or focal versus non-focal subphenotypes in adult patients were included. Quality of studies was evaluated using the QUADAS-2 tool. Statistical analyses were performed using "Mada" in Rstudio, version 4.0.3. Sensitivity and specificity with 95% confidence interval of each separate study were summarized in a Forest plot. RESULTS: The search resulted in 2648 unique records. After selection, 11 reports were included, involving 2075 patients and 598 ARDS cases (29%). Nine studies reported on ARDS diagnosis and two reported on focal versus non-focal ARDS subphenotypes classification. Meta-analysis showed a pooled sensitivity of 0.631 (95% CI 0.450-0.782) and pooled specificity of 0.942 (95% CI 0.856-0.978) of LUS for ARDS diagnosis. In two studies, LUS could accurately differentiate between focal versus non-focal ARDS subphenotypes. Insufficient data was available to perform a meta-analysis. CONCLUSION: This review confirms the hypothesis that LUS is a reliable method for diagnosing ARDS in adult patients. For the classification of focal or non-focal subphenotypes, LUS showed promising results, but more research is needed.

Associations of early changes in lung ultrasound aeration scores and mortality in invasively ventilated patients: a post hoc analysis.

BACKGROUND: Lung ultrasound (LUS) in an emerging technique used in the intensive care unit (ICU). The derivative LUS aeration score has been shown to have associations with mortality in invasively ventilated patients. This study assessed the predictive value of baseline and early changes in LUS aeration scores in critically ill invasively ventilated patients with and without ARDS (Acute Respiratory Distress Syndrome) on 30- and 90-day mortality. METHODS: This is a post hoc analysis of a multicenter prospective observational cohort study, which included patients admitted to the ICU with an expected duration of ventilation for at least 24 h. We restricted participation to patients who underwent a 12-region LUS exam at baseline and had the primary endpoint (30-day mortality) available. Logistic regression was used to analyze the primary and secondary endpoints. The analysis was performed for the complete patient cohort and for predefined subgroups (ARDS and no ARDS). RESULTS: A total of 442 patients were included, of whom 245 had a second LUS exam. The baseline LUS aeration score was not associated with mortality (1.02 (95% CI: 0.99 - 1.06), p = 0.143). This finding was not different in patients with and in patients without ARDS. Early deterioration of the LUS score was associated with mortality (2.09 (95% CI: 1.01 - 4.3), p = 0.046) in patients without ARDS, but not in patients with ARDS or in the complete patient cohort. CONCLUSION: In this cohort of critically ill invasively ventilated patients, the baseline LUS aeration score was not associated with 30- and 90-day mortality. An early change in the LUS aeration score was associated with mortality, but only in patients without ARDS. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT04482621.

Heterogeneity of treatment effect of vilobelimab in COVID-19: a secondary analysis of a randomised controlled trial.

In a phase 3 trial (PANAMO, NCT04333420), vilobelimab, a complement 5a (C5a) inhibitor, reduced 28-day mortality in mechanically ventilated COVID-19 patients. This post hoc analysis of 368 patients aimed to explore treatment heterogeneity through unsupervised learning. All available clinical variables at baseline were used as input. Treatment heterogeneity was assessed using latent class analysis (LCA), Ward's hierarchical clustering (HC) and the adjudication to previously described clinical sepsis phenotypes. The primary outcome was 28-day mortality. For LCA, a 2-class latent model was deemed most suitable. In the LCA model, 82 (22%) patients were assigned to class 1 and 286 (78%) to class 2. Class 1 was defined by more severely ill patients with significantly higher mortality. In an adjusted logistic regression, no heterogeneity of treatment effect (HTE) between classes was observed (p = 0.998). For HC, no significant classes were found (p = 0.669). Using the previously described clinical sepsis subtypes, 41 patients (11%) were adjudicated subtype alpha (α), 17 (5%) beta (ß), 112 (30%) delta (δ) and 198 (54%) gamma (γ). HTE was observed between clinical subtypes (p = 0.001) with improved 28-day mortality after treatment with vilobelimab for the δ subtype (OR = 0.17, 95% CI 0.07-0.40, p < 0.001). No signal for harm of treatment with vilobelimab was observed in any class or clinical subtype. Overall, treatment effect with vilobelimab was consistent across different classes and subtypes, except for the δ subtype, suggesting potential additional benefit for the most severely ill patients.

Post-mortem changes of anisotropic mechanical properties in the porcine brain assessed by MR elastography.

Knowledge of the mechanical properties of brain tissue in vivo is essential to understanding the mechanisms underlying traumatic brain injury (TBI) and to creating accurate computational models of TBI and neurosurgical simulation. Brain white matter, which is composed of aligned, myelinated, axonal fibers, is structurally anisotropic. White matter in vivo also exhibits mechanical anisotropy, as measured by magnetic resonance elastography (MRE), but measurements of anisotropy obtained by mechanical testing of white matter ex vivo have been inconsistent. The minipig has a gyrencephalic brain with similar white matter and gray matter proportions to humans and therefore provides a relevant model for human brain mechanics. In this study, we compare estimates of anisotropic mechanical properties of the minipig brain obtained by identical, non-invasive methods in the live (in vivo) and dead animals (in situ). To do so, we combine wave displacement fields from MRE and fiber directions derived from diffusion tensor imaging (DTI) with a finite element-based, transversely-isotropic nonlinear inversion (TI-NLI) algorithm. Maps of anisotropic mechanical properties in the minipig brain were generated for each animal alive and at specific times post-mortem. These maps show that white matter is stiffer, more dissipative, and more anisotropic than gray matter when the minipig is alive, but that these differences largely disappear post-mortem, with the exception of tensile anisotropy. Overall, brain tissue becomes stiffer, less dissipative, and less mechanically anisotropic post-mortem. These findings emphasize the importance of testing brain tissue properties in vivo. Statement of Significance: In this study, MRE and DTI in the minipig were combined to estimate, for the first time, anisotropic mechanical properties in the living brain and in the same brain after death. Significant differences were observed in the anisotropic behavior of brain tissue post-mortem. These results demonstrate the importance of measuring brain tissue properties in vivo as well as ex vivo, and provide new quantitative data for the development of computational models of brain biomechanics.

Mannose-Presenting "Glyco-Colicins" Convert the Bacterial Cell Surface into a Multivalent Adsorption Site for Adherent Bacteria.

Biofilm formation is integral to the pathogenesis of numerous adherent bacteria and contributes to antimicrobial resistance (AMR). The rising threat of AMR means the need to develop novel nonbactericidal antiadhesion approaches against such bacteria is more urgent than ever. Both adherent-invasive Escherichia coli (AIEC, implicated in inflammatory bowel disease) and uropathogenic E. coli (UPEC, responsible for ∼80% of urinary tract infections) adhere to terminal mannose sugars on epithelial glycoproteins through the FimH adhesin on their type 1 pilus. Although mannose-based inhibitors have previously been explored to inhibit binding of adherent bacteria to epithelial cells, this approach has been limited by monovalent carbohydrate-protein interactions. Herein, we pioneer a novel approach to this problem through the preparation of colicin E9 bioconjugates that bind to the abundant BtuB receptor in the outer membrane of bacteria, which enables multivalent presentation of functional motifs on the cell surface. We show these bioconjugates label the surface of live E. coli and furthermore demonstrate that mannose-presenting "glyco-colicins" induce E. coli aggregation, thereby using the bacteria, itself, as a multivalent platform for mannose display, which triggers binding to adjacent FimH-presenting bacteria.

Associative white matter tracts selectively predict sensorimotor learning.

Human learning varies greatly among individuals and is related to the microstructure of major white matter tracts in several learning domains, yet the impact of the existing microstructure of white matter tracts on future learning outcomes remains unclear. We employed a machine-learning model selection framework to evaluate whether existing microstructure might predict individual differences in learning a sensorimotor task, and further, if the mapping between tract microstructure and learning was selective for learning outcomes. We used diffusion tractography to measure the mean fractional anisotropy (FA) of white matter tracts in 60 adult participants who then practiced drawing a set of 40 unfamiliar symbols repeatedly using a digital writing tablet. We measured drawing learning as the slope of draw duration over the practice session and measured visual recognition learning for the symbols using an old/new 2-AFC task. Results demonstrated that tract microstructure selectively predicted learning outcomes, with left hemisphere pArc and SLF3 tracts predicting drawing learning and the left hemisphere MDLFspl predicting visual recognition learning. These results were replicated using repeat, held-out data and supported with complementary analyses. Results suggest that individual differences in the microstructure of human white matter tracts may be selectively related to future learning outcomes.

Optimisation of pharmacotherapy in psychiatry through therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests: focus on antipsychotics.

BACKGROUND: For psychotic disorders (i.e. schizophrenia), pharmacotherapy plays a key role in controlling acute and long-term symptoms. To find the optimal individual dose and dosage strategy, specialized tools are used. Three tools have been proven useful to personalize drug treatments: therapeutic drug monitoring (TDM) of drug levels, pharmacogenetic testing (PG), and molecular neuroimaging. METHODS: In these Guidelines, we provide an in-depth review of pharmacokinetics, pharmacodynamics, and pharmacogenetics for 50 antipsychotics. Over 30 international experts in psychiatry selected studies that have measured drug concentrations in the blood (TDM), gene polymorphisms of enzymes involved in drug metabolism, or receptor/transporter occupancies in the brain (positron emission tomography (PET)). RESULTS: Study results strongly support the use of TDM and the cytochrome P450 (CYP) genotyping and/or phenotyping to guide drug therapies. Evidence-based target ranges are available for titrating drug doses that are often supported by PET findings. CONCLUSION: All three tools discussed in these Guidelines are essential for drug treatment. TDM goes well beyond typical indications such as unclear compliance and polypharmacy. Despite its enormous potential to optimize treatment effects, minimize side effects and ultimately reduce the global burden of diseases, personalized drug treatment has not yet become the standard of care in psychiatry.

[Current status of tuberculosis burden in China].

Tuberculosis, caused by Mycobacterium tuberculosis, is an infectious disease that most often affects the lungs. China is still among the high-burden tuberculosis countries in the world. Although the estimated incidence of tuberculosis in China has declined in recent years, the declining rate is slow. It still faces major issues such as a slower rate of decline, a widening gap between estimated and notified incidence, higher risk among middle-aged and older adults, a high number of cases among agriculture and related workers, and a heavier disease burden in the country's western regions. In addition, latent tuberculosis infection, drug-resistant tuberculosis, tuberculosis coinfection with HIV, and extrapulmonary tuberculosis have also exacerbated the disease burden of tuberculosis to some extent. This paper reviewed the epidemic characteristics of tuberculosis, the epidemiological triad, three links and two factors in the transmission process, the disease burden, and other aspects to provide a reference for formulating prevention and control strategies on tuberculosis.

Combination Targeted Therapy with Lenvatinib and Pembrolizumab in Progressive, Radioiodine-Refractory Differentiated Thyroid Cancers.

PURPOSE: Lenvatinib, a potent multi-kinase inhibitor, improves progression-free survival (PFS) in patients with radioiodine (RAI)-refractory differentiated thyroid cancer (DTC); however, most patients experience disease progression, warranting further therapy. We evaluated the efficacy and safety of combination lenvatinib plus pembrolizumab (LP) in these patients. PATIENTS AND METHODS: We enrolled patients with progressive, RAI-refractory DTC that were either naïve to multi-kinase inhibitors (cohort 1) or who had progressed on lenvatinib (cohort 2). Patients received oral lenvatinib daily (cohort 1, 20 mg; cohort 2, dose at progression ) and intravenous pembrolizumab (200 mg) every 21 days. RESULTS: 30 and 27 patients were enrolled in cohort 1 and 2, respectively. Adverse events were consistent with those observed in other cancers. In cohort 1, the confirmed overall response rate (ORR) was 65.5%. There were no complete responses (CR, primary endpoint). The 12 and 18-month PFS were 72.0% and 58.0%, respectively, and median PFS was 26.8 months. In cohort 2, the confirmed ORR was 16% (primary endpoint), and median PFS was 10.0 months (95% CI; 7.0-17.9 months). Tumor histology, driver mutations, and immune-related biomarkers, including PD-L1 expression, thyroid-specific antibody levels, and CD8+ T cell tumor infiltrate, did not correlate with response to therapy. Increased baseline peripheral blood monocytes and neutrophil to lymphocyte ratio were associated with a worse PFS in cohort 1. CONCLUSIONS: Combination lenvatinib plus pembrolizumab may enhance the durability of lenvatinib monotherapy in lenvatinib-naïve patients. Furthermore, the addition of pembrolizumab may be a viable salvage therapy for patients who have progressed on lenvatinib.

Sunitinib for the treatment of metastatic gastrointestinal stromal tumors: the effect of TDM-guided dose optimization on clinical outcomes.

BACKGROUND: Sunitinib is an oral anticancer drug approved for the treatment of among others gastrointestinal stromal tumor (GIST). Previous analyses demonstrated an exposure-response relationship at the standard dose, and minimum target levels of drug exposure have been defined above which better treatment outcomes are observed. Therapeutic drug monitoring (TDM) could be used as a tool to optimize the individual dose, aiming at sunitinib trough concentrations ≥37.5 ng/ml for continuous dosing. Nonetheless, data on the added value of TDM-guided dosing on clinical endpoints are currently lacking. Therefore, we evaluate the effect of TDM in patients with advanced and metastatic GIST treated with sunitinib in terms of efficacy and toxicity. PATIENTS AND METHODS: A TDM-guided cohort was compared to a non-TDM-guided cohort in terms of median progression-free survival (mPFS) and overall survival (mOS). Also, mPFS between patients with and without dose-limiting toxicities (DLTs) was compared. Patients in the prospective cohort were included in two studies on TDM-guided dosing (the DPOG-TDM study and TUNE study). The retrospective cohort consisted of patients from the Dutch GIST Registry who did not receive TDM-guided dosing. RESULTS: In total, 51 and 106 patients were included in the TDM-guided cohort and non-TDM-guided cohort, respectively. No statistical difference in mPFS was observed between these two cohorts (39.4 versus 46.9 weeks, respectively; P = 0.52). Patients who experienced sunitinib-induced DLTs had longer mPFS compared to those who did not (51.9 versus 28.9 weeks, respectively; P = 0.002). CONCLUSIONS: Our results do not support the routine use of TDM-guided dose optimization of sunitinib in patients with advanced/metastatic GIST to improve survival.

ExMove: An open-source toolkit for processing and exploring animal-tracking data in R.

Ongoing technological advances have led to a rapid increase in the number, type and scope of animal-tracking studies. In response, many software tools have been developed to analyse animal movement data. These tools generally focus on movement modelling, but the steps required to clean raw data files from different tracking devices have been largely ignored. Such pre-processing steps are often time-consuming and involve a steep learning curve but are crucial for the creation of high-quality, standardised and shareable data. Moreover, decisions made at this early stage can substantially influence subsequent analyses, and in the current age of reproducibility crisis, the transparency of this process is vital. Here we present an open-access, reproducible toolkit written in the programming language R for processing raw data files into a single cleaned data set for analyses and upload to online tracking databases (found here: https://github.com/ExMove/ExMove). The toolkit comprises well-documented and flexible code to facilitate data processing and user understanding, both of which can increase user confidence and improve the uptake of sharing open and reproducible code. Additionally, we provide an overview website (found here: https://exmove.github.io/) and a Shiny app to help users visualise tracking data and assist with parameter determination during data cleaning. The toolkit is generalisable to different data formats and device types, uses modern 'tidy coding' practices, and relies on a few well-maintained packages. Among these, we perform spatial manipulations using the package sf. Overall, by collating all required steps from data collection to archiving on open access databases into a single, robust pipeline, our toolkit provides a valuable resource for anyone conducting animal movement analyses and represents an important step towards increased standardisation and reproducibility in animal movement ecology.

Complete genome sequences of two closely related isolates of Staphylococcus saprophyticus isolated from human fingertips.

Complete genomes of two closely related isolates of Staphylococcus saprophyticus from human fingertips, SZ.YL11 and SZ.PL35w, were established through hybrid assembly. Each possesses a single circular chromosome and a circular plasmid, totaling 2,611,553 and 2,611,619 bp, respectively (with G + C 33.14% for both).