We introduce monosaccharides as versatile water‐soluble units to compatibilise supramolecular polymers based on the benzene‐1,3,5‐tricarboxamide (BTA) moiety with water. A library of ...monosaccharide‐based BTAs is evaluated, varying the length of the alkyl chain (hexyl, octyl, decyl and dodecyl) separating the BTA and saccharide units, as well as the saccharide units (α‐glucose, β‐glucose, α‐mannose and α‐galactose). In all cases, the monosaccharides impart excellent water compatibility. The length of the alkyl chain is the determining factor to obtain either long, one‐dimensional supramolecular polymers (dodecyl spacer), small aggregates (decyl spacer) or molecularly dissolved (octyl and hexyl) BTAs in water. For the BTAs comprising a dodecyl spacer, our results suggest that a cooperative self‐assembly process is operative and that the introduction of different monosaccharides does not significantly change the self‐ assembly behaviour. Finally, we investigate the potential of post‐assembly functionalisation of the formed supramolecular polymers by taking advantage of dynamic covalent bond formation between the monosaccharides and benzoxaboroles. We observe that the supramolecular polymers readily react with a fluorescent benzoxaborole derivative permitting imaging of these dynamic complexes by confocal fluorescence microscopy.
Sugar‐coating BTAs: Functionalising the periphery of benzene‐1,3,5‐tricarboxamide (BTA) with monosaccharides affords high aspect ratio supramolecular polymers in water, which are readily post‐modified using benzoxaboroles by dynamic covalent chemistry (see figure).
Recent excavations at the early Middle Pleistocene site of Mata Menge in the So'a Basin of central Flores, Indonesia, have yielded hominin fossils attributed to a population ancestral to Late ...Pleistocene Homo floresiensis. Here we describe the age and context of the Mata Menge hominin specimens and associated archaeological findings. The fluvial sandstone layer from which the in situ fossils were excavated in 2014 was deposited in a small valley stream around 700 thousand years ago, as indicated by (40)Ar/(39)Ar and fission track dates on stratigraphically bracketing volcanic ash and pyroclastic density current deposits, in combination with coupled uranium-series and electron spin resonance dating of fossil teeth. Palaeoenvironmental data indicate a relatively dry climate in the So'a Basin during the early Middle Pleistocene, while various lines of evidence suggest the hominins inhabited a savannah-like open grassland habitat with a wetland component. The hominin fossils occur alongside the remains of an insular fauna and a simple stone technology that is markedly similar to that associated with Late Pleistocene H. floresiensis.
Wastewater surveillance for pathogens using reverse transcription-polymerase chain reaction (RT-PCR) is an effective and resource-efficient tool for gathering community-level public health ...information, including the incidence of coronavirus disease-19 (COVID-19). Surveillance of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in wastewater can potentially provide an early warning signal of COVID-19 infections in a community. The capacity of the world's environmental microbiology and virology laboratories for SARS-CoV-2 RNA characterization in wastewater is increasing rapidly. However, there are no standardized protocols or harmonized quality assurance and quality control (QA/QC) procedures for SARS-CoV-2 wastewater surveillance. This paper is a technical review of factors that can cause false-positive and false-negative errors in the surveillance of SARS-CoV-2 RNA in wastewater, culminating in recommended strategies that can be implemented to identify and mitigate some of these errors. Recommendations include stringent QA/QC measures, representative sampling approaches, effective virus concentration and efficient RNA extraction, PCR inhibition assessment, inclusion of sample processing controls, and considerations for RT-PCR assay selection and data interpretation. Clear data interpretation guidelines (e.g., determination of positive and negative samples) are critical, particularly when the incidence of SARS-CoV-2 in wastewater is low. Corrective and confirmatory actions must be in place for inconclusive results or results diverging from current trends (e.g., initial onset or reemergence of COVID-19 in a community). It is also prudent to perform interlaboratory comparisons to ensure results' reliability and interpretability for prospective and retrospective analyses. The strategies that are recommended in this review aim to improve SARS-CoV-2 characterization and detection for wastewater surveillance applications. A silver lining of the COVID-19 pandemic is that the efficacy of wastewater surveillance continues to be demonstrated during this global crisis. In the future, wastewater should also play an important role in the surveillance of a range of other communicable diseases.
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•Harmonized QA/QC procedures for SARS-CoV-2 wastewater surveillance are lacking.•Wastewater analysis protocols are not optimized for trace analysis of viruses.•False-positive and -negative errors have consequences for public health responses.•Inter-laboratory studies utilizing standardized reference materials and protocols are needed.
The relationship between cannabis use and cognitive functioning in patients with psychosis has yielded contradictory findings. In individuals at genetic high risk for psychosis, information is ...sparse. The aim of this study was to assess the association between recency and frequency of cannabis use and cognitive functioning in patients with psychosis and their unaffected siblings.
We conducted a cross-sectional study in 956 patients with non-affective psychosis, 953 unaffected siblings, and 554 control subjects. Participants completed a cognitive test battery including assessments of verbal learning, set shifting, sustained attention, processing speed, working memory, acquired knowledge, reasoning and problem solving and social cognition. Cannabis use was assessed by urinalysis and by the Composite International Diagnostic Interview. Using random-effect regression models the main effects of cannabis (recency and frequency) and the interaction with status (patient, sibling, control) on cognitive functioning were assessed.
Current cannabis use was associated with poorer performance on immediate verbal learning, processing speed and working memory (Cohen's d -0.20 to -0.33, p<0.005). Lifetime cannabis use was associated with better performance on acquired knowledge, facial affect recognition and face identity recognition (Cohen's d+0.17 to +0.33, p<0.005). There was no significant interaction between cannabis and status on cognitive functioning.
Lifetime cannabis-using individuals might constitute a subgroup with a higher cognitive potential. The residual effects of cannabis may impair short-term memory and processing speed.
Bioluminescent molecular beacons have been developed using a modular design approach that relies on BRET between the bright luciferase NanoLuc and a Cy3 acceptor. While classical molecular beacons ...are hampered by background fluorescence and scattering, these BRET-beacons allow detection of low pM concentrations of nucleic acids directly in complex media.
Background Current management of autosomal dominant polycystic kidney disease (ADPKD) is focused on treating disease complications, not on slowing cyst development or preventing progression to kidney ...failure. Tolvaptan, a selective vasopressin V2 (vasopressin 2) receptor antagonist, has been proved to inhibit kidney cyst growth and preserve kidney function in multiple animal models of polycystic kidney disease. The TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) 3-4 Study will examine the long-term effectiveness and safety of tolvaptan in patients with ADPKD. We report baseline characteristics and revised power calculations for the trial. Study Design A prospective, 3-year, multicenter, double-blind, placebo-controlled trial of tolvaptan, a selective V2 receptor antagonist. Primary outcome is total kidney volume percentage of change from baseline for tolvaptan relative to placebo. Secondary outcome parameters include time to ADPKD-associated complications (kidney function decrease, blood pressure control, renal pain, and albuminuria) and safety end points. Setting & Participants This trial includes patients with ADPKD with relatively preserved kidney function (baseline estimated creatinine clearance ≥60 mL/min), aged 50 years or younger, and with total kidney volume measured using magnetic resonance imaging ≥750 mL. Intervention Administration of placebo or tolvaptan, dose titrated to tolerance. Outcomes Number of subjects enrolled and baseline characteristics. Measurements Total kidney volume, kidney function, albuminuria, kidney pain, and vital signs. Results 1,445 patients with ADPKD were enrolled between March 2007 and January 2009. Preliminary baseline median total kidney volume was 1.46 L, and estimated creatinine clearance was 105 ± 34 mL/min. A prespecified blinded sample-size recalculation at two-thirds enrollment confirmed the likely power of the study to detect 20% differences from placebo in the primary and key secondary end points at P < 0.05. Limitations This is a preselected ADPKD population chosen for its risk of progression to kidney failure and may not represent the general ADPKD population. If study results are positive with regard to the primary end point, positive effects on other secondary clinical outcomes will be required to assess overall benefit. Conclusions This randomized trial is the largest clinical study of a proposed ADPKD intervention to date. It targets patients with ADPKD with early disease who are projected to have rapid cyst growth and accelerated outcomes. Blockade of vasopressin V2 receptor is hypothesized to inhibit cyst growth, thereby delaying additional adverse clinical outcomes.
Pregnant women diagnosed with CIN3 have high regression rates after delivery. Biomarkers are needed to only identify pregnant women with progressive CIN requiring treatment to reduce overreferral and ...overtreatment. In our study we evaluated the performance of the FAM19A4/miR124‐2 methylation test for molecular triage on FFPE samples of CIN3+‐diagnosed pregnant women with known clinical course over time as well in a cross‐sectional setting. In this German multicenter retrospective study biopsy material was collected from pregnant women diagnosed with cervical cancer (n = 16), with CIN3 that progressed to cancer during pregnancy (n = 7), with CIN3 that regressed to CIN1 or less within 6 months after delivery (n = 41), without CIN (n = 16), CIN3 covering 3‐4 quadrants (n = 14) and randomly selected CIN3 (n = 41). FAM19A4/miR124‐2 methylation analysis was performed blinded on first diagnosis. All pregnant women with cervical cancer and with CIN3 progressing to cancer tested positive for FAM19A4/miR124‐2 methylation (100%, 22/22). In the regressing CIN3 group 47.5% and in the group without CIN 21.6% tested methylation positive. High‐volume CIN3 and random selected CIN3 were methylation‐positive in 91.7% and 82.1%, respectively. Methylation levels were significantly higher in progressive CIN3 and cancer compared to the controls (P < .0005). The likelihood ratio of a negative methylation test (LR−) for progressive CIN3+ was 0 (95% CI: 0‐0.208). A negative FAM19A4/miR124‐2 methylation test can rule out progressive CIN disease in pregnant women diagnosed with CIN3. This can help the clinician by managing these pregnant women with conservative follow‐up until after delivery.
What's new?
Pregnant women with cervical intraepithelial neoplasia grade 3 (CIN3) area big challange to the gynecologists in order to find an individual treatment that does no harm to neither the woman nor her unborn child. This study shows that a negative FAM19A4/miR124‐2 methylation test can rule out progressive CIN3 and cervical cancer and that a negative FMA19A4/miR124‐2 test can help the clinician safely managing these pregnant women with conservative follow‐up until after delivery.
Scenario‐based biodiversity modelling is a powerful approach to evaluate how possible future socio‐economic developments may affect biodiversity. Here, we evaluated the changes in terrestrial ...biodiversity intactness, expressed by the mean species abundance (MSA) metric, resulting from three of the shared socio‐economic pathways (SSPs) combined with different levels of climate change (according to representative concentration pathways RCPs): a future oriented towards sustainability (SSP1xRCP2.6), a future determined by a politically divided world (SSP3xRCP6.0) and a future with continued global dependency on fossil fuels (SSP5xRCP8.5). To this end, we first updated the GLOBIO model, which now runs at a spatial resolution of 10 arc‐seconds (~300 m), contains new modules for downscaling land use and for quantifying impacts of hunting in the tropics, and updated modules to quantify impacts of climate change, land use, habitat fragmentation and nitrogen pollution. We then used the updated model to project terrestrial biodiversity intactness from 2015 to 2050 as a function of land use and climate changes corresponding with the selected scenarios. We estimated a global area‐weighted mean MSA of 0.56 for 2015. Biodiversity intactness declined in all three scenarios, yet the decline was smaller in the sustainability scenario (−0.02) than the regional rivalry and fossil‐fuelled development scenarios (−0.06 and −0.05 respectively). We further found considerable variation in projected biodiversity change among different world regions, with large future losses particularly for sub‐Saharan Africa. In some scenario‐region combinations, we projected future biodiversity recovery due to reduced demands for agricultural land, yet this recovery was counteracted by increased impacts of other pressures (notably climate change and road disturbance). Effective measures to halt or reverse the decline of terrestrial biodiversity should not only reduce land demand (e.g. by increasing agricultural productivity and dietary changes) but also focus on reducing or mitigating the impacts of other pressures.
We project the changes in terrestrial biodiversity intactness from 2015 to 2050 corresponding with three of the shared socio‐economic pathways combined with different levels of climate change, using an updated version of the GLOBIO model. Biodiversity intactness declined in all three scenarios, with large losses particularly for sub‐Saharan Africa. Effective measures to halt or reverse the decline of terrestrial biodiversity should not only reduce land demand but also reduce or mitigate the impacts of other pressures.
Integrated 2-18 F-fluoro-2-deoxy- d -glucose (FDG) PET/CT and magnetic resonance imaging (MRI) with functional features of diffusion-weighted imaging (DWI) are advancing imaging technologies that ...have current and future potential to overcome important limitations of conventional staging methods in the management of patients with oesophageal cancer. PET/CT has emerged as an important part of the standard work-up of patients with oesophageal cancer. Besides its important ability to detect unsuspected metastatic disease, PET/CT may be useful in the assessment of treatment response, radiation treatment planning, and detection of recurrent disease. In addition, high-resolution T2-weighted MRI and DWI have potential complementary roles. Recent improvements in MRI protocols and techniques have resulted in better imaging quality with the potential to bring improvement in staging, radiation treatment planning, and the assessment of treatment response. Optimal use and understanding of PET/CT and MRI in oesophageal cancer will contribute to the impact of these advancing technologies in tailoring treatment to the individual patient and achieving best possible outcomes. In this article, we graphically outline the current and potential future roles of PET/CT and MRI in the multidisciplinary management of oesophageal cancer.
As part of a worldwide survey of the indoor mycobiota, dust was collected from nine countries. Analyses of dust samples included the culture-dependent dilution-to-extinction method and the ...culture-independent 454-pyrosequencing. Of the 7 904 isolates, 2 717 isolates were identified as belonging to Aspergillus, Penicillium and Talaromyces. The aim of this study was to identify isolates to species level and describe the new species found. Secondly, we wanted to create a reliable reference sequence database to be used for next-generation sequencing projects. Isolates represented 59 Aspergillus species, including eight undescribed species, 49 Penicillium species of which seven were undescribed and 18 Talaromyces species including three described here as new. In total, 568 ITS barcodes were generated, and 391 β-tubulin and 507 calmodulin sequences, which serve as alternative identification markers.
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