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New direct-acting antivirals have the potential to transform the hepatitis C (HCV) treatment landscape, with rates of sustained viral response in excess of 90%. As these new agents are expensive, an important question is whether to focus on minimizing the consequences of severe liver disease, or reducing transmission via 'treatment as prevention'. A back-calculation model was used to estimate the impact of treatment of mild, moderate and compensated cirrhosis on incident cases of HCV-related end-stage liver disease/hepatocellular carcinoma (ESLD/HCC). In addition, a dynamic model was used to determine the impact on incidence and prevalence of chronic infection in people who inject drugs (PWID), the main risk group in England. Treating 3500 cirrhotics per year was predicted to reduce ESLD/HCC incidence from 1100 (95% CrI 970-1240) cases per year in 2015 to 630 (95% CrI 530-770) in 2020, around half that currently expected, although treating moderate-stage disease will also be needed to sustain this reduction. Treating mild-stage PWID was required to make a substantial impact on transmission: with 2500 treated per year, chronic prevalence/annual incidence in PWID was reduced from 34%/4.8% in 2015 to 11%/1.4% in 2030. There was little overlap between the two goals: treating mild stage had virtually no impact on ESLD/HCC within 15 years, but the long timescale of liver disease means relatively few PWID reach cirrhosis before cessation of injecting. Strategies focussing on treating advanced disease have the potential for dramatic reductions in severe morbidity, but virtually no preventative impact.

Purpose: Diffusion magnetic resonance imaging (MRI) and 6-[18F]fluoro-l-dopa ([18F]FDOPA) positron emission tomography (PET) are used to interrogate malignant tumor microenvironment. It remains unclear whether there is a relationship between [18F]FDOPA uptake, diffusion MRI estimates of apparent diffusion coefficient (ADC), and mitotic activity in the context of recurrent malignant gliomas, where the tumor may be confounded by the effects of therapy. The purpose of the current study is to determine whether there is a correlation between these imaging techniques and mitotic activity in malignant gliomas.Procedures: We retrospectively examined 29 patients with recurrent malignant gliomas who underwent structural MRI, diffusion MRI, and [18F]FDOPA PET prior to surgical resection. Qualitative associations were noted, and quantitative voxel-wise and median measurement correlations between [18F]FDOPA PET, ADC, and mitotic index were performed.Results: Areas of high [18F]FDOPA uptake exhibited low ADC and areas of hyperintensity T2/fluid-attenuated inversion recovery (FLAIR) with low [18F]FDOPA uptake exhibited high ADC. There was a significant inverse voxel-wise correlation between [18F]FDOPA and ADC for all patients. Median [18F]FDOPA uptake and median ADC also showed a significant inverse correlation. Median [18F]FDOPA uptake was positively correlated, and median ADC was inversely correlated with mitotic index from resected tumor tissue.Conclusions: A significant association may exist between [18F]FDOPA uptake, diffusion MRI, and mitotic activity in recurrent malignant gliomas.

Bevacizumab is a therapeutic drug used in treatment of recurrent glioblastoma to inhibit angiogenesis. Treatment response is often monitored through the use of perfusion MRI measures of cerebral blood volume, flow, and other pharmacokinetic parameters; however, most methods for deriving these perfusion parameters can produce errors depending on bolus kinetics. Recently, a number of new methods have been developed to overcome these challenges. In the current study we examine cerebral blood volume and blood flow characteristics in 45 recurrent glioblastoma patients before and after treatment with bevacizumab. Perfusion MRI data was processed using a standard single value decomposition (SVD) technique, two block-circulant SVD techniques, and a Bayesian estimation technique. A proportional hazards model showed that patients with a large decrease in relative blood volume (RBV) after treatment had extended overall survival (P = 0.0048). Patients with large pre-treatment relative blood flow (RBF) showed extended progression-free survival (P = 0.0216) and overall survival (P = 0.0112), and patients with a large decrease in RBF following treatment showed extended overall survival (P = 0.0049). These results provide evidence that blood volume and blood flow measurements can be used as biomarkers in patients treated with bevacizumab.

Background and purposePre-treatment ADC characteristics have been shown to predict response to bevacizumab in recurrent glioblastoma multiforme. However, no studies have examined whether ADC characteristics are specific to this particular treatment. The purpose of the current study was to determine whether ADC histogram analysis is a bevacizumab-specific or treatment-independent biomarker of treatment response in recurrent glioblastoma multiforme.Materials and methodsEighty-nine bevacizumab-treated and 43 chemotherapy-treated recurrent glioblastoma multiformes never exposed to bevacizumab were included in this study. In all patients, ADC values in contrast-enhancing ROIs from MR imaging examinations performed at the time of recurrence, immediately before commencement of treatment for recurrence, were extracted and the resulting histogram was fitted to a mixed model with a double Gaussian distribution. Mean ADC in the lower Gaussian curve was used as the primary biomarker of interest. The Cox proportional hazards model and log-rank tests were used for survival analysis.ResultsCox multivariate regression analysis accounting for the interaction between bevacizumab- and non-bevacizumab-treated patients suggested that the ability of the lower Gaussian curve to predict survival is dependent on treatment (progression-free survival, P = .045; overall survival, P = .003). Patients with bevacizumab-treated recurrent glioblastoma multiforme with a pretreatment lower Gaussian curve > 1.2 μm(2)/ms had a significantly longer progression-free survival and overall survival compared with bevacizumab-treated patients with a lower Gaussian curve < 1.2 μm(2)/ms. No differences in progression-free survival or overall survival were observed in the chemotherapy-treated cohort. Bevacizumab-treated patients with a mean lower Gaussian curve > 1.2 μm(2)/ms had a significantly longer progression-free survival and overall survival compared with chemotherapy-treated patients.ConclusionsThe mean lower Gaussian curve from ADC histogram analysis is a predictive imaging biomarker for bevacizumab-treated, not chemotherapy-treated, recurrent glioblastoma multiforme. Patients with recurrent glioblastoma multiforme with a mean lower Gaussian curve > 1.2 μm(2)/ms have a survival advantage when treated with bevacizumab.

Background and purposeTumor location is a significant prognostic factor in glioblastoma, which may reflect the genetic profile of tumor precursor cells. The purpose of the current study was to construct and analyze probabilistic radiographic atlases reflecting preoperative tumor locations and corresponding demographic, "-omic," and interventional phenotypes to provide insight into potential niche locations of glioblastoma cells of origin.Materials and methodsPreoperative anatomic MR images in 507 patients with de novo glioblastoma were analyzed. Images were registered to stereotactic space, tumors were segmented, and the stereospecific frequency of tumor occurrence was analyzed statistically by age, extent of resection, MGMT methylation, IDH1 mutation, gene expression subclassification, PTEN loss, PTEN deficiency, EGFR amplification, EGFR variant 3 expression, progression-free survival from the start of radiochemotherapy, and overall survival from initial diagnosis.ResultsMost glioblastomas grow into the periventricular white matter regions adjacent to the subventricular zone. MGMT promoter methylated tumors occur more frequently in the left temporal lobe, in young patients with glioblastoma, in IDH1 mutant tumors, in tumors having the proneural gene expression subtype, and in tumors lacking loss of PTEN occurring most frequently in the frontal lobe. MGMT methylated tumors with the IDH1 mutation tended to occur in the left frontal lobe. EGFR amplified and EGFR variant 3-expressing tumors occurred most frequently in the left temporal lobe. A similar region in the left temporal lobe was associated with favorable response to radiochemotherapy and increased survival.ConclusionsRadiographic atlases for specific phenotypes provide insight into overlap between prognostic variables and may help to identify niche locations for cancer cells of origin.

The purpose of this study was to compare the clinical root coverage achieved with two connective tissue grafts that were removed from the same donor area at different times and used in subepithelial grafts for root coverage. Sixty patients, each of whom had two connective tissue grafts removed from the same donor area at different times, were included in this study. The connective tissue grafts were used in two different subepithelial grafts for root coverage. The subepithelial grafts with both the first and second connective tissue grafts produced statistically significant changes in recession, probing depth, width of keratinized tissue, and attachment level. The changes obtained in the clinical measurements were not statistically significantly different between the first and second connective tissue grafts. The mean percentages of root coverage with the first and second connective tissue grafts were 95.4% and 98.2%, respectively, a statistically significant difference. None of the factors evaluated (sex, age, smoking history, and time between the two surgeries) could be related to statistically significant differences in the mean root coverage obtained. In this study, the second connective tissue graft produced greater mean root coverage than the first connective tissue graft. [ABSTRACT FROM AUTHOR]

The goal of this study was to evaluate the clinical changes obtained when intra-bony defects were treated with an enamel matrix derivative (EMD), a bone graft, and guided tissue regeneration. Fifty patients with a periodontal defect not associated with a furcation and with an attachment loss of at least 7.0 mm were included in this study. Full-thickness flaps were reflected, the roots were planed, EMD was applied, a demineralized freeze-dried bone allograft combined with EMD was placed, a bioabsorbable membrane was placed, and more EMD was applied. The defect areas were then sutured. At a mean of 5.3 months after treatment, there was a mean increase in recession of 0.7 mm, a mean reduction in probing depth of 5.7 mm, and a mean gain in attachment level of 5.0 mm. In this study there was more recession in smokers than in nonsmokers and in defects associated with anterior teeth. Additionally, the deeper defects (those with greater probing depths and attachment level loss) had the greatest reductions in probing depth and gains in attachment level. Based on this study, this technique proved itself to be an effective method to improve the clinical situation when treating periodontal defects not involving furcations. [ABSTRACT FROM AUTHOR]

The goal of this study was to evaluate the incidence and severity of the complications that occur after connective tissue grafts are used. Five hundred consecutively treated patients, for whom connective tissue grafts were used for root coverage or gingival augmentation, were included in this study. Complications did occur, but the rates and intensities seemed clinically acceptable. There was no pain reported in 81.4% of the patients, no bleeding in 97.0% of the patients, no infection in 99.2% of the patients, and no swelling in 94.6% of the patients. None of the factors evaluated in this study were associated with a statistically significant increase in the rate or intensity of complications. These factors included: age, sex of patient, smoking status, purpose of the graft (ie, for root coverage or for gingival augmentation), size of the recipient area, and the location of the defect being treated. Based on the results of this study, the incidence and severity of complications seemed to be clinically acceptable. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate two variations of the subepithelial graft. Two hundred consecutively treated patients received subepithelial grafts to obtain root coverage. One hundred patients were treated with connective tissue grafts combined with double pedicle grafts. The other 100 patients were treated with connective tissue grafts combined with coronally positioned pedicle grafts. The mean root coverages were 97.6% and 96.1%, respectively. When the overlying pedicle was a double pedicle, there was a larger increase in the amount of keratinized tissue (3.0 mm versus 1.8 mm). When the preoperative recession depth was 5.0 mm or greater and a connective tissue graft was combined with a coronally positioned pedicle, there was less mean root coverage. The results of this study confirm that the subepithelial graft is an effective method to obtain root coverage. Additionally, the type of pedicle used to cover the connective tissue graft can affect the results. [ABSTRACT FROM AUTHOR]

The purpose of this study was to histologically evaluate furcation defects in humans treated with an allograft-alloplast-tetracycline composite graft combined with an absorbable membrane for guided tissue regeneration (GTR). Three teeth with Class II furcation involvement on the buccal aspects were included in this study. A notch was placed in calculus during the procedure to serve as a reference point for histologic evaluation. The defects were then treated with an allograft-alloplast-tetracycline composite graft combined with an absorbable membrane for GTR. At 6 months postoperative, the teeth were extracted with conservative block sections and processed for histologic evaluation. Regeneration (new bone, cementum, and connective tissue attachment) coronal to a notch could be seen in one of the three defects treated. In the other two defects, a new connective tissue attachment was demonstrated (new connective tissue attachment into new cementum) in the notch placed in calculus. In this study, regeneration of a furcation defect in a human was documented with histology. [ABSTRACT FROM AUTHOR]

The goal of this study was to evaluate the long-term stability of the root coverage results obtained with an acellular dermal matrix. The mean root coverage at 12 weeks postoperative was 91.7%. The mean root coverage at the final postoperative evaluation (mean 18.6 months) was 87.0%. This difference was not statistically or clinically significant. The root coverage results obtained with an acellular dermal matrix were predictable, esthetic, and stable over time. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the long-term stability of the results obtained when guided tissue regeneration (GTR) is used to obtain root coverage. A mean root coverage of 92.3% was obtained at 6 months postoperative. However, at the final postoperative visit (mean 25.3 months), the mean root coverage was reduced to 58.8%. This difference was statistically and clinically significant. There was a statistically significant increase in recession (1.4 mm) and a statistically significant loss in attachment levels (1.7 mm) between the 6-month and final postoperative evaluations. The results of this study question the long-term stability of the result when GTR is used for root coverage. [ABSTRACT FROM AUTHOR]

Treatment of a cracked tooth can be difficult and unpredictable. Quite often, the most predictable treatment possible is simply extraction. This is a case report of the treatment of a cracked tooth with a resin-ionomer restoration and a connective tissue with partial-thickness double pedicle graft. The crack was detected during a routine root coverage procedure using this type of graft. A resin-ionomer was used to repair the crack. Then, the root coverage procedure was completed. Complete root coverage was obtained, including the portion of the root that was repaired. The results remained stable and the tooth treated remained asymptomatic. Clinically, the treatment was a success. [ABSTRACT FROM AUTHOR]

There are many possible goals and outcomes of periodontal surgical therapy, but the ultimate goal is regeneration. Since the definition of periodontal regeneration is histologic, it is difficult to document. The purpose of this study was to evaluate a technique that combined a bone graft and guided tissue regeneration (GTR) to see if regeneration occurred. Four teeth with dehiscence-type osseous defects that were scheduled for extraction were treated with bone grafts and GTR. During the surgical procedure, a notch was placed into the root at the apical extent of the calculus. The teeth were extracted with conservative block sections 7 months after the treatment. They were processed, sectioned, stained, and evaluated histologically. The results revealed that regeneration did not occur in any of the teeth treated. In 2 of the teeth new connective tissue attachment was formed. In these 2 teeth cementum could be seen in the notch with connective tissue fibers inserting into the cementum. In one of the teeth the junctional epithelium extended apical to the notch, while in 3 cases the epithelium stopped at or coronal to the notch. In this case report, no regeneration could be documented, but new attachment could be seen in 2 of the 4 teeth treated. [ABSTRACT FROM AUTHOR]

Background We examined whether determinants of disease progression and causes of death differ between injecting drug users (IDUs) and non-IDUs who initiate combination antiretroviral therapy (cART). Methods The ART Cohort Collaboration combines data from participating cohort studies on cART-naïve adults from cART initiation. We used Cox models to estimate hazard ratios for death and AIDS among IDUs and non-IDUs. The cumulative incidence of specific causes of death was calculated and compared using methods that allow for competing risks. Results Data on 6269 IDUs and 37 774 non-IDUs were analysed. Compared with non-IDUs, a lower proportion of IDUs initiated cART with a CD4 cell count <200 cells/μL or had a prior diagnosis of AIDS. Mortality rates were higher in IDUs than in non-IDUs (2.08 vs. 1.04 per 100 person-years, respectively; P<0.001). Lower baseline CD4 cell count, higher baseline HIV viral load, clinical AIDS at baseline, and later year of cART initiation were associated with disease progression in both groups. However, the inverse association of baseline CD4 cell count with AIDS and death appeared stronger in non-IDUs than in IDUs. The risk of death from each specific cause was higher in IDUs than non-IDUs, with particularly marked increases in risk for liver-related deaths, and those from violence and non-AIDS infection. Conclusion While liver-related deaths and deaths from direct effects of substance abuse appear to explain much of the excess mortality in IDUs, they are at increased risk for many other causes of death, which may relate to suboptimal management of HIV disease in these individuals. [ABSTRACT FROM AUTHOR]

In salt marsh ecosystems, daggerblade grass shrimp, Palaemon (Palaemonetes) pugio, play a crucial role in food webs and serve as the definitive host for the bopyrid isopod Probopyrus pandalicola. These ectoparasites infest the branchial chambers of grass shrimp, which can lead to decreased energy availability and sterilization of infected hosts. Although bopyrid isopod infestation of daggerblade grass shrimp has been frequently reported in literature from coastal marshes of the southeastern United States, the prevalence of this parasite has not been recently documented in daggerblade grass shrimp from marshes of the northeastern United States. The goal of this project was to quantify the prevalence of Pr. pandalicola infestations in Pa. pugio across Cape Cod, Massachusetts. We evaluated bopyrid isopod prevalence from shrimp collected from 5 different salt marsh habitats along Cape Cod in August 2021. Bopyrid isopod infestations were found in shrimp at 4 of 5 salt marshes, with prevalence ranging from 0.04 to 14.1%. Seasonal resampling of one of the salt marshes revealed the highest average infestation prevalence in spring (<17.1%) and an isolated high of 30.3% prevalence in a single salt panne. A series of linear and multivariate models showed that panne area, shrimp abundance, and distance to shoreline were related to Pr. pandalicola shrimp infestations in salt pannes in summer. This study describes the prevalence of the bopyrid isopod infesting daggerblade grass shrimp in salt marshes in New England, with implications for how parasitized shrimp influence salt marsh food webs in which they are found., (© American Society of Parasitologists 2024.)

Background: There is limited empirical work assessing the effectiveness of treatment as prevention (TasP) in reducing HCV prevalence among people who inject drugs (PWID). Here, we used survey data from the UK during 2010-2020, to evaluate the impact of direct-acting antiviral agent (DAA) treatment scale-up, which started in 2015, on HCV prevalence among PWID., Methods: We fitted a logistic regression to time/location specific data on prevalence from the Needle Exchange Surveillance Initiative in Scotland and Unlinked Anonymous Monitoring programme in England. For each post-intervention year and location, we quantified the effect of TasP as the difference between estimated prevalence and its counterfactual (prevalence in the absence of scale-up). Progress to elimination was assessed by comparing most recent prevalence against one in 2015., Results: In 2015, prevalence ranged from 0.44 to 0.71 across the 23 locations (3 Scottish, 20 English). Compared to counterfactuals, there was an absolute reduction of 46% (95% credible interval [32%,59%]) in Tayside in 2020, 35% ([24%,44%]) in Glasgow in 2019, and 25% ([10%,39%]) in the Rest of Scotland in 2020. The English sites with highest estimated absolute reductions in 2021 were South Yorkshire (45%, [29%,58%]), Thames Valley (49%, [34%,59%]) and West London (41%, [14%,59%]). Compared to 2015, there was 80% probability that prevalence had fallen by 65% in Tayside, 53% in Glasgow and 36% in the Rest of Scotland. The English sites with highest % prevalence decrease compared to 2015, achieved with probability 80%, were Chesire & Merseyside (70%), South Yorkshire (65%) and Thames Valley (71%). Higher treatment intensity was associated with higher reductions in prevalence., Conclusion: Conclusion. Real-world evidence showing substantial reductions in chronic HCV associated with increase of HCV treatment scale-up in the community thus supporting the effectiveness of HCV treatmen as prevention in people who inject drugs., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: The introduction of new direct-acting antivirals for hepatitis C virus (HCV) infection, has enabled the formulation of a HCV elimination strategy led by the World Health Organisation (WHO). Guidelines for elimination of HCV target a reduction in incidence, but this is difficult to measure and needs estimating., Methods: Serial cross-sectional bio-behavioural sero-surveys provide information on an individual's infection status and duration of exposure and how these change over time. These data can be used to estimate the rate of first infection through appropriate statistical models. This study utilised updated HCV seroprevalence information from the Unlinked Anonymous Monitoring survey, an annual survey of England, Wales and Northern Ireland monitoring the prevalence of blood borne viruses in people who inject drugs. Flexible parametric and semiparametric approaches, including fractional polynomials and splines, for estimating incidence rates by exposure time and survey year were implemented and compared., Results: Incidence rates were shown to peak in those recently initiating injecting drug use at approximately 0.20 infections per person-year followed by a rapid reduction in the subsequent few years of injecting to approximately 0.05 infections per person-year. There was evidence of a rise in incidence rates for recent initiates between 2011 and 2020 from 0.17 infections per person-year (95 % CI, 0.16-0.19) to 0.26 infections per person-year (0.23-0.30). In those injecting for longer durations, incidence rates were stable over time., Conclusions: Fractional polynomials provided an adequate fit with relatively few parameters, but splines may be preferable to ensure flexibility, in particular, to detect short-term changes in the rate of first infection over time that may be a result of treatment effects. Although chronic HCV prevalence has declined with treatment scale up over 2016-2020, there is no evidence yet of a corresponding fall in the rate of first infection. Seroprevalence and risk behaviour data can be used to estimate and monitor HCV incidence, providing insight into progress towards WHO defined elimination of HCV., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Snakes in the family Elapidae largely produce venoms rich in three-finger toxins (3FTx) that bind to the α 1 subunit of nicotinic acetylcholine receptors (nAChRs), impeding ion channel activity. These neurotoxins immobilize the prey by disrupting muscle contraction. Coral snakes of the genus Micrurus are specialist predators who produce many 3FTx, making them an interesting system for examining the coevolution of these toxins and their targets in prey animals. We used a bio-layer interferometry technique to measure the binding interaction between 15 Micrurus venoms and 12 taxon-specific mimotopes designed to resemble the orthosteric binding region of the muscular nAChR subunit. We found that Micrurus venoms vary greatly in their potency on this assay and that this variation follows phylogenetic patterns rather than previously reported patterns of venom composition. The long-tailed Micrurus tend to have greater binding to nAChR orthosteric sites than their short-tailed relatives and we conclude this is the likely ancestral state. The repeated loss of this activity may be due to the evolution of 3FTx that bind to other regions of the nAChR. We also observed variations in the potency of the venoms depending on the taxon of the target mimotope. Rather than a pattern of prey-specificity, we found that mimotopes modeled after snake nAChRs are less susceptible to Micrurus venoms and that this resistance is partly due to a characteristic tryptophan → serine mutation within the orthosteric site in all snake mimotopes. This resistance may be part of a Red Queen arms race between coral snakes and their prey., (© 2024. The Author(s).)

Purpose: Childhood exposure to domestic violence and abuse (DVA) can lead to major short- and long-term effects on the victim. Despite this, there is no accepted measure for children's experiences, with most existing measures being validated only in high income countries and not in low- and middle- income countries. As a result, international statistics are not comparable. This paper seeks to critically appraise existing measures and discuss whether any are fit-for-purpose on a global scale., Method: The COSMIN PROMs approach was followed to critically appraise and compare the appropriateness of measures. A comprehensive literature search was undertaken in seven journal databases for measures mentioned in formally peer-reviewed articles exploring childhood exposure to DVA., Results: A literature search resulted in the identification of 10 measures and, following criteria to only keep original measures and remove modifications, four measures which have been validated cross-culturally are discussed in detail in line with the COSMIN PROMs criterion: The Child Exposure to Domestic Violence Scale, Children's Perception of Interparental Conflict Scale, Juvenile Victimization Questionnaire and The Violence Exposure Scale for Children. Strengths and limitations of each are discussed, along with any validations undertaken not in the country of origin., Conclusion: Despite childhood exposure to DVA being an urgent research priority worldwide, the current measures to explore the extent of the issue are not validated cross-culturally, leading to concerns about comparisons across different population groups. The development and implementation of interventions to reduce the levels and effects of exposure relies heavily on cross-cultural comparisons, which may indicate different strategies are needed in different contexts. The lack of these validated comparisons is constraining advances, and the paper advocates for further efforts to be made in this regard., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Harris, Channon and Morgan.)

We evaluated the effects of Roundup QuikPRO™ (73.3 % glyphosate) using real-world herbicide application treatments: (1) overspray (low-dose), (2) powder spill (high-dose), and (3) controls (no-dose). Seagrass and water quality were monitored to observe responses to acute herbicide application. Seagrass shoot densities significantly declined over time in high-dose treatments, whereas seagrass shoot densities in low-dose treatments were comparable to controls. In high-dose treatments, seagrass mortality increased over time, 100 % Halophila ovalis and 81 % Halodule wrightii mortality from day zero to 53. Collectively, glyphosate concentrations were negatively correlated with seagrass shoot densities, and positively correlated with water column nutrients (TN and TP). Based on these results we do not attribute local seagrass declines to low-dose glyphosate exposure, i.e., herbicide overspray events. However, we advise caution against improper herbicide handling, since glyphosate remained detectable in relatively high concentrations (<88 mg/L) after 53 days, resulting in seagrass mortality and increased water column nutrients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Histone modifications influence the recruitment of reader proteins to chromosomes to regulate events including transcription and cell division. The idea of a histone code, where combinations of modifications specify unique downstream functions, is widely accepted and can be demonstrated in vitro. For example, on synthetic peptides, phosphorylation of Histone H3 at threonine-3 (H3T3ph) prevents the binding of reader proteins that recognize trimethylation of the adjacent lysine-4 (H3K4me3), including the TAF3 component of TFIID. To study these combinatorial effects in cells, we analyzed the genome-wide distribution of H3T3ph and H3K4me2/3 during mitosis. We find that H3T3ph anti-correlates with adjacent H3K4me2/3 in cells, and that the PHD domain of TAF3 can bind H3K4me2/3 in isolated mitotic chromatin despite the presence of H3T3ph. Unlike in vitro, H3K4 readers are still displaced from chromosomes in mitosis in Haspin-depleted cells lacking H3T3ph. H3T3ph is therefore unlikely to be responsible for transcriptional downregulation during cell division., (© 2023. The Author(s).)

B cells are known to contribute to the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized in these cancers to detail. Here we show comprehensive phenotyping in samples of circulating and tumor-resident B cells as well as serum antibodies in melanoma patients. Memory B cells are enriched in tumors compared to blood in paired samples and feature distinct antibody repertoires, linked to specific isotypes. Tumor-associated B cells undergo clonal expansion, class switch recombination, somatic hypermutation and receptor revision. Compared with blood, tumor-associated B cells produce antibodies with proportionally higher levels of unproductive sequences and distinct complementarity determining region 3 properties. The observed features are signs of affinity maturation and polyreactivity and suggest an active and aberrant autoimmune-like reaction in the tumor microenvironment. Consistent with this, tumor-derived antibodies are polyreactive and characterized by autoantigen recognition. Serum antibodies show reactivity to antigens attributed to autoimmune diseases and cancer, and their levels are higher in patients with active disease compared to post-resection state. Our findings thus reveal B cell lineage dysregulation with distinct antibody repertoire and specificity, alongside clonally-expanded tumor-infiltrating B cells with autoimmune-like features, shaping the humoral immune response in melanoma., (© 2023. The Author(s).)

Global water scarcity necessitates creative, yet practical, solutions to meet ever-growing demand. Green infrastructure is increasingly used in this context to provide water in environmentally friendly and sustainable ways. In this study, we focused on reclaimed wastewater from a joint gray and green infrastructure system employed by the Loxahatchee River District in Florida. The water system consists of a series of treatment stages for which we assessed 12 years of monitoring data. We measured water quality after secondary (gray) treatment, then in onsite lakes, offsite lakes, landscape irrigation (via sprinklers), and ultimately in downstream canals. Our findings show gray infrastructure designed for secondary treatment, integrated with green infrastructure, achieved nutrient concentrations nearly equivalent to advanced wastewater treatment systems. For example, we observed a dramatic decline in mean nitrogen concentration from 19.42 mg L -1 after secondary treatment to 5.26 mg L -1 after spending an average of 30 days in the onsite lakes. Nitrogen concentration continued to decline as reclaimed water moved from onsite lakes to offsite lakes (3.87 mg L -1 ) and irrigation sprinklers (3.27 mg L -1 ). Phosphorus concentrations exhibited a similar pattern. These decreasing nutrient concentrations led to relatively low nutrient loading rates and occurred while consuming substantially less energy and producing fewer greenhouse gas emissions than traditional gray infrastructure-at lower cost and higher efficiency. There was no evidence of eutrophication in canals downstream of the residential landscape whose sole source of irrigation water was reclaimed water. This study provides a long-term example of how circularity in water use can be used to work toward sustainable development goals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Venoms are complex chemical arsenals that have evolved independently many times in the animal kingdom. Venoms have attracted the interest of researchers because they are an important innovation that has contributed greatly to the evolutionary success of many animals, and their medical relevance offers significant potential for drug discovery. During the last decade, venom research has been revolutionized by the application of systems biology, giving rise to a novel field known as venomics. More recently, biotechnology has also made an increasing impact in this field. Its methods provide the means to disentangle and study venom systems across all levels of biological organization and, given their tremendous impact on the life sciences, these pivotal tools greatly facilitate the coherent understanding of venom system organization, development, biochemistry, and therapeutic activity. Even so, we lack a comprehensive overview of major advances achieved by applying biotechnology to venom systems. This review therefore considers the methods, insights, and potential future developments of biotechnological applications in the field of venom research. We follow the levels of biological organization and structure, starting with the methods used to study the genomic blueprint and genetic machinery of venoms, followed gene products and their functional phenotypes. We argue that biotechnology can answer some of the most urgent questions in venom research, particularly when multiple approaches are combined together, and with other venomics technologies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lüddecke, Paas, Harris, Talmann, Kirchhoff, Billion, Hardes, Steinbrink, Gerlach, Fry and Vilcinskas.)