Clinical trials in depression lack objective measures. Speech latencies are an objective measure of psychomotor slowing with face validity and empirical support. \'Turn latency\' is the response time between speakers. Retrospective analysis was carried-out on the utility of turn latencies as an enrichment tool in a clinical trial of bipolar I depression. Speech data was obtained from 274 participants during 1,352 Montgomery-Åsberg Depression Rating Scale (MADRS) recordings in a randomized, placebo controlled, 6-week clinical trial of SEP-4199 (200 mg or 400 mg). Post-randomization turn latencies were compared between patients with moderate to severe depression and patients whose depression had remitted. A cutoff was determined and applied to turn latencies pre-randomization to classify individuals into two groups: Speech Latencies Slow (SL-Slow) and Speech Latencies Normal (SL-Normal). At week 6, SL-Slow (N = 172) showed significant separation in MADRS scores between placebo and treatment arms. SL-Normal (N = 102) showed larger MADRS improvements and no significant separation between placebo and treatment arms. Excluding SL-Normal increased primary outcome effect size by 52 % and 100 % for the treatment arms. Turn latencies are an objective measure available from standard clinical assessments and may assess the severity of symptoms more accurately and screen out placebo responders.

A novel and facile surface molecularly imprinted polymer coated on magnetic chitosan (Fe3O4@CS@MIP) was fabricated for the selective recognition and enrichment of naringin (NRG). The Fe3O4@CS@MIP was prepared based on covalent-noncovalent synergistic imprinting strategies, utilizing 4-vinyl phenyl boric acid as covalent functional monomer, deep eutectic solvent (choline chloride/methacrylic acid [ChCl/MAA]) as non-covalent functional monomer and Fe3O4@CS nanoparticles as the magnetic support. The obtained Fe3O4@CS@MIP exhibited a uniform morphology, excellent crystallinity, outstanding magnetic properties, and high surface area. Owing to the double recognition abilities, the resultant polymer showed exceptional binding performance and rapid mass transfer in phosphate buffer (pH 7.0). The maximum binding amount of Fe3O4@CS@MIP was found to be 15.08 mg g-1, and the equilibrium adsorption could be achieved within 180 min. Moreover, they also exhibited stronger selectivity for NRG and satisfactory reusability, with only 11.0% loss after five adsorption-desorption cycles. Additionally, the Fe3O4@CS@MIP, serving as an adsorbent, presented practical application potential in the separation and enrichment of NRG from pummelo peel, with extraction efficiency in the range of 79.53% to 84.63%. This work provided a new strategy for improving the performance of MIP and contributed an attractive option for the extraction of NRG in complex samples.

The sea surface microlayer (SML), particularly in monsoon-influenced regions, remains largely unexplored. This study aims to determine the concentrations, enrichment, and factors controlling the enrichment processes of surface-active substances (SASs), which include surfactants, dissolved monosaccharides (MCHOs), polysaccharides (PCHOs), total dissolved carbohydrates (TDCHOs), and transparent exopolymer particles (TEPs) around the coastal area of Malaysian Peninsula. The SML samples and underlying water (ULW) from a depth of 1 m were collected during the southwest (August and September 2023) and northeast (November 2023) monsoons. Surfactants, TEPs, and dissolved carbohydrates were measured spectrometrically using methylene blue, the Alcian blue assay, and 2,4,6-Tri(2-pyridyl)-s-triazine (TPTZ), respectively. The results showed that stations influenced by anthropogenic activities were generally enriched with surfactants (Enrichment factor, EF = 1.40 ± 0.91) and carbohydrate species (TDCHOs = 1.38 ± 0.28, MCHOs = 1.54 ± 0.57, PCHOs = 1.85 ± 1.43). However, TEP enrichment was not observed in our study (EF = 0.68 ± 0.24). The SASs in the SML were correlated with their underlying concentrations, implying that transport from underlying water could be a major source of substances in the SML. High carbohydrate concentrations and enrichment were found during the northeast monsoon, implying that rain and runoff water affect concentrations in the SML. Besides, the enrichment of SASs persists at moderate wind speeds and is depleted at high wind speeds.

OBJECTIVE: Novel interventions for the prevention or treatment of acute kidney injury (AKI) are currently lacking. To facilitate the evaluation and adoption of new treatments, the use of the most appropriate design and endpoints for clinical trials in AKI is critical and yet there is little consensus regarding these issues. We aimed to develop recommendations on endpoints and trial design for studies of AKI prevention and treatment interventions based on existing data and expert consensus.
METHODS: At the 31st Acute Disease Quality Initiative (ADQI) meeting, international experts in critical care, nephrology, involving adults and pediatrics, biostatistics and people with lived experience (PWLE) were assembled. We focused on four main areas: (1) patient enrichment strategies, (2) prevention and attenuation studies, (3) treatment studies, and (4) innovative trial designs of studies other than traditional (parallel arm or cluster) randomized controlled trials. Using a modified Delphi process, recommendations and consensus statements were developed based on existing data, with > 90% agreement among panel members required for final adoption.
RESULTS: The panel developed 12 consensus statements for clinical trial endpoints, application of enrichment strategies where appropriate, and inclusion of PWLE to inform trial designs. Innovative trial designs were also considered.
CONCLUSIONS: The current lack of specific therapy for prevention or treatment of AKI demands refinement of future clinical trial design. Here we report the consensus findings of the 31st ADQI group meeting which has attempted to address these issues including the use of predictive and prognostic enrichment strategies to enable appropriate patient selection.

The Greater Sydney (Australia) region is dissected by eleven major estuaries comprising a wide range of sizes, sediment and contaminant types, while the catchments also vary in size, land use type, populations size and geology/soils. The magnitude and breadth of the current study are rare and offered an unusual opportunity to provide new information on interactions between source, fate and effect relationships of a highly diverse estuarine-catchment environment using sedimentary metals (Co, Cr, Cu, Ni, Pb and Zn). Advanced methodologies used in this study revealed that although metal concentrations were generally high, ecological risk was surprisingly reduced due to the presence of metal-poor coarse sediment. Stormwater was identified as the dominant source of metals to estuaries of Greater Sydney and relates to development of high-density road networks. Industrial sources, frequently identified as a major contributor to estuarine contamination, was significantly reduced due to the decline of industry through decentralisation and gentrification and because waste is discharged to the sewer system, which is released offshore, or tertiary-treated to the Hawkesbury. Groundwater leachate associated with shoreline reclamation and wetland infilling and metals related to boating activities were important sources of metals impacting local bays and coastal lagoons. Temporal monitoring and unique modelling approaches indicated that the concentration of sedimentary metals is generally declining in these estuaries, (especially for Pb), except for areas with rapidly increasing urban populations. Multivariate statistical modelling was able to differentiate the 11 estuaries on a chemical basis by aligning Cu, Pb, Zn vectors with metal-rich estuaries and also identified catchment attributes (percent area, total yield, anthropogenic yield and population density) normalised to catchment areas as having a major influence on estuarine condition. The new knowledge derived from this study should be used to assess the environmental status of estuaries and to prioritise management actions in future investigations.

BACKGROUND: Clinical trial scenarios can be modeled using data from observational studies, providing critical information for design of real-world trials. The Huntington\'s Disease Integrated Staging System (HD-ISS) characterizes disease progression over an individual\'s lifespan and allows for flexibility in the design of trials with the goal of delaying progression. Enrichment methods can be applied to the HD-ISS to identify subgroups requiring smaller estimated sample sizes.
OBJECTIVE: Investigate time to the event of functional decline (HD-ISS Stage 3) as an endpoint for trials in HD and present sample size estimates after enrichment.
METHODS: We classified individuals from observational studies according to the HD-ISS. We assessed the ability of the prognostic index normed (PIN) and its components to predict time to HD-ISS Stage 3. For enrichment, we formed groups from deciles of the baseline PIN distribution for HD-ISS Stage 2 participants. We selected enrichment subgroups closer to Stage 3 transition and estimated sample sizes, using delay in the transition time as the effect size.
RESULTS: In predicting time to HD-ISS Stage 3, PIN outperforms its components. Survival curves for each PIN decile show that groups with PIN from 1.48 to 2.74 have median time to Stage 3 of approximately 2 years and these are combined to create enrichment subgroups. Sample size estimates are presented by enrichment subgroup.
CONCLUSIONS: PIN is predictive of functional decline. A delay of 9 months or more in the transition to Stage 3 for an enriched sample yields feasible sample size estimates, demonstrating that this approach can aid in planning future trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

UNASSIGNED: Chronic kidney disease (CKD) burden is crucial both on a global scale and at individual patient level, affecting morbidity and mortality directly and through its effect on both cardiovascular damage and CKD progression to end-stage-kidney-disease (ESKD). Unfortunately, the awareness of CKD is poor, with few CKD patients conscious of the severity of their health status. The principal biomarker of kidney function is estimated glomerular filtration rate (eGFR).
UNASSIGNED: We searched the literature and present a review article with the aim of summarizing the role of eGFR in clinical research. In particular, we report the eGFR role as a prognostic, enrichment and endpoint biomarker and its role in the early detection of CKD.
UNASSIGNED: eGFR has a major role as a biomarker in clinical research. As a prognostic marker, eGFR reduction is associated with cardiovascular events, ESKD and mortality. As an enrichment biomarker, eGFR values are pivotal for selecting patients to be included in randomized and observational studies; it helps to test a pre-defined drug in early CKD or in more advanced CKD allowing also to avoid screening failures and to shorten the duration of clinical trials. Moreover, eGFR decline (expressed as a percentage of reduction from baseline or continuous slope) can be considered a good endpoint in clinic trials overcoming delays whilst waiting for hard endpoints to develop.
UNASSIGNED: eGFR is a strong clinical measure for both observational and intervention studies. It is also helpful in screening the general population for kidney disease and, in particular, to increase awareness of CKD.

Both natural and anthropogenic activities are responsible for heavy metal abundance in the environment. Due to the high persistence, heavy metals can accumulate and remain in the sediment for very long periods, becoming a source of contaminants for aquatic biota. Within small urbanized watercourse catchments, the accumulation of heavy metals in bottom sediments takes place and sediments can be adopted as an efficient indicator for monitoring heavy metal pollution levels and pollution sources in aquatic environments. Tiber River, the most polluted river among the 20 longest Italian rivers, has different tributaries distributed from north to south of Rome city. The aim of the study was to evaluate the heavy metal pollution in water and sediment of six Tiber River small tributaries through the use of land cover, water physico-chemical parameters and geochemical multi-index (Concentration factor, Pollution Load index, Enrichment factor and Geoaccumulation index). The results indicate that in general the contamination of water and sediments is moderate as the threshold values are exceeded only by some metals and in some sites. As regards the indices that evaluate the enrichment factors, it has been seen that some sampling sites have high values of specific metal enrichment (As, Hg, Pb). A more compromised situation is highlighted by the Concentration Factor and the Pollution Load index where more than half of the sampling sites are found at levels of significant heavy metal pollution suggesting that point sources of heavy metals in the water and sediments should be closely monitored by the use of combined analysis.

Rare earth elements (REEs) have attracted much attention because of their unique physical and chemical properties. The root system is the plant organ most directly in contact with REEs, and it is critical to understand the mechanisms of interaction between the two. This paper investigates the effects of REEs on plant enrichment and fractionation, as well as on various developmental and toxicity indices of the root system. REEs are more likely to be deposited on the root surface under the influence of root secretion. The complexation between the two affects the uptake and fractionation of REEs and the altered pattern of root secretion. The toxicity mechanisms of REEs on plant root cells were lied in: (1) REEs generate reactive oxygen species after entering the plant, leading to oxidative stress and damage to plant cells; (2) REEs with higher charge-to-volume ratios compete for organic ligands with or displace Ca2+, further disrupting the normal function of plant root cells. It was shown that the sensitivity of inter-root microorganisms to REEs varied depending on the content and physicochemical properties of REEs. The paper also concluded with a meta-analysis of phytotoxicity induced by REEs, which showed that REEs affect plant physiological parameters. REEs, as a source of oxidative stress, triggered lipid peroxidation damage in plants and enhanced the activity of antioxidant enzymes, thus revealing the significant toxicity of REEs to plants. The phytotoxic effects of REEs increased with time and concentration. These results help to elucidate the ecotoxicology of rare earth-induced phytotoxicity.

Ricin is a toxic protein regarded as a potential chemical weapon for bioterrorism or criminal use. In the event of a ricin incident, rapid analytical methods are essential for ricin confirmation in a diversity of matrices, from environmental to human or food samples. Mass spectrometry-based methods provide specific toxin identification but require prior enrichment by antibodies to reach trace-level detection in matrices. Here, we describe a novel assay using the glycoprotein asialofetuin as an alternative to antibodies for ricin enrichment, combined with the specific detection of signature peptides by high-resolution mass spectrometry. Additionally, optimizations made to the assay reduced the sample preparation time from 5 h to 80 min only. Method evaluation confirmed the detection of ricin at trace levels over a wide range of pH and in protein-rich samples, illustrating challenging matrices. This new method constitutes a relevant antibody-free solution for the fast and specific mass spectrometry detection of ricin in the situation of a suspected toxin incident, complementary to active ricin determination by adenine release assays.