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Microplastics (MPs) are an emerging environmental issue due to their accumulation in ecosystems and living organisms. Increasing evidence shows that MPs impact vascular function, with recent studies finding MPs in atheromas linked to cardiovascular events. Since vascular smooth muscle cells (VSMCs) are crucial to maintaining vascular function, this study examined how MPs activate VSMCs, leading to cardiovascular diseases like atherosclerosis and vascular calcification. The study used polyethylene (PE) and polystyrene (PS), common in food packaging, as "virgin" or photo-degraded to simulate environmental conditions. VSMC viability, apoptosis, cytotoxicity, inflammation, and activation markers were evaluated. PE and PS affected VSMC viability, induced apoptosis, and triggered pathological changes such as altered migration and proliferation. Key markers like RUNX-2 and galectin-3, which regulate cardiovascular pathology, were activated, alongside the inflammasome complex. In conclusion, MPs can induce harmful activation of VSMCs, posing potential health risks through inflammation, cell damage, and phenotypic changes. Understanding these toxic mechanisms may reveal critical pathways for intervention and prevention. [ABSTRACT FROM AUTHOR]

Alexander disease (ALXDRD) is a rare neurodegenerative disorder of astrocytes resulting from pathogenic variants in the GFAP gene. The genotype-phenotype correlation remains elusive due to the variable expressivity of clinical manifestations. In an attempt to clarify the effects of GFAP variants in ALXDRD, numerous studies were collected and analyzed. In particular, we systematically searched for GFAP variants associated with ALXDRD and collected information on the location within the gene and protein, prediction of deleteriousness/pathogenicity, occurrence, sex and country of origin of patients, DNA source, genetic testing, and clinical signs. To identify possible associations, statistical analyses and meta-analyses were applied, thus revealing a higher than expected percentage of adult patients with ALXDRD. Furthermore, substitution of Arginine, the most frequently altered residue among the 550 predominantly missense causative GFAP variants collected, were mostly de novo and more prevalent in early-onset forms of ALXDRD. The effect of defective splicing in modifying the impact of GFAP variants on the age of onset of ALXDRD was also postulated after evaluating the distribution of the corresponding deleterious predictive values. In conclusion, not only previously unrecognized genotype-phenotype correlations were revealed in ALXDRD, but also subtle mechanisms could explain the variable manifestations of the ALXDRD clinical phenotype. [ABSTRACT FROM AUTHOR]

Marsh lateral expansion and retreat are often attributed to sediment availability, but a causal link is difficult to establish. To shed light on this problem, we analyzed changes in salt marsh area along the ~ 200-km-long Georgia coast (USA) from the 1850s to 2010s in relation to total suspended sediment (TSS) and to proxies for river sediment input and local sediment resuspension. Marsh area is characterized by large gains and losses (up to 200 m2/m/yr), but relatively small net change (-50 to 50 m2/m/yr or -0.1 to 0.1%/yr). This has resulted in a general loss of marsh area, except close to the mouths of major rivers, where there is net gain. Net expansion rates decreased in the Savannah Estuary but increased in the Altamaha Estuary from the 1850s–1930s period to the 1930s–2010s period, which are consistent with observed decreases and likely increases in sediment discharge in the two estuaries, respectively. To explain the spatial patterns in the 1930s–2010s marsh area change, we estimated TSS from satellite measurements (2003 to 2020). Along the northern part of the Georgia coast, net marsh gain is positively correlated to the average TSS within the estuarine region. However, this correlation breaks down in more southern areas (Cumberland Sound). Coast-wide, there is a better correlation between TSS associated with new input from the rivers, estimated as the TSS difference between high-discharge (Jan–Mar) and low-discharge (Sept–Nov) months. To identify the effect of wave resuspension in the nearshore, we consider the TSS difference between high-wave, low-discharge (Sept–Nov) and low-wave, low-discharge periods (Jun–Aug). Wave resuspension is relatively uniform along the coast and does not explain spatial patterns of marsh area change. Sediment input from the nearshore is likely contributing to the estuarine sediment budget in Georgia, but it is not sufficient to prevent marsh lateral retreat. To identify the role of tidal resuspension and advection, we consider differences in TSS between low and high tide. This differential is relatively constant along most of the coast, but it is much lower in the southern part of the coast, suggesting a lower tidal action in this region. Sediment resuspended by tides is likely originating from internal recycling (i.e., erosion) within the estuary, and thus does not contribute to marsh lateral expansion. The proposed approach to partition TSS is a general demonstration and could be applied to other coastal regions. [ABSTRACT FROM AUTHOR]

Tropical forest degradation from selective logging, fire and edge effects is a major driver of carbon and biodiversity loss1–3, with annual rates comparable to those of deforestation4. However, its actual extent and long-term impacts remain uncertain at global tropical scale5. Here we quantify the magnitude and persistence of multiple types of degradation on forest structure by combining satellite remote sensing data on pantropical moist forest cover changes4 with estimates of canopy height and biomass from spaceborne6 light detection and ranging (LiDAR). We estimate that forest height decreases owing to selective logging and fire by 15% and 50%, respectively, with low rates of recovery even after 20 years. Agriculture and road expansion trigger a 20% to 30% reduction in canopy height and biomass at the forest edge, with persistent effects being measurable up to 1.5 km inside the forest. Edge effects encroach on 18% (approximately 206 Mha) of the remaining tropical moist forests, an area more than 200% larger than previously estimated7. Finally, degraded forests with more than 50% canopy loss are significantly more vulnerable to subsequent deforestation. Collectively, our findings call for greater efforts to prevent degradation and protect already degraded forests to meet the conservation pledges made at recent United Nations Climate Change and Biodiversity conferences.A global survey on the magnitude and persistence of moist forest cover change and canopy height following degradation using satellite remote sensing data finds that the effects are substantial and persist for decades. [ABSTRACT FROM AUTHOR]

Accessible SARS-CoV-2-specific immunoassays may inform clinical management in people with HIV, particularly in case of persisting immunodysfunction. We prospectively studied their application in vaccine recipients with HIV, purposely including participants with a history of advanced HIV infection. Participants received one (n = 250), two (n = 249) or three (n = 42) doses of the BNT162b2 vaccine. Adverse events were documented through questionnaires. Sample collection occurred pre-vaccination and a median of 4 weeks post-second dose and 14 weeks post-third dose. Anti-spike and anti-nucleocapsid antibodies were measured with the Roche Elecsys chemiluminescence immunoassays. Neutralising activity was evaluated using the GenScript cPass surrogate virus neutralisation test, following validation against a Plaque Reduction Neutralization Test. T-cell reactivity was assessed with the Roche SARS-CoV-2 IFNγ release assay. Primary vaccination (2 doses) was well tolerated and elicited measurable anti-spike antibodies in 202/206 (98.0%) participants. Anti-spike titres varied widely, influenced by previous SARS-CoV-2 exposure, ethnicity, intravenous drug use, CD4 counts and HIV viremia as independent predictors. A third vaccine dose significantly boosted anti-spike and neutralising responses, reducing variability. Anti-spike titres > 15 U/mL correlated with neutralising activity in 136/144 paired samples (94.4%). Three participants with detectable anti-S antibodies did not develop cPass neutralising responses post-third dose, yet displayed SARS-CoV-2 specific IFNγ responses. SARS-CoV-2 vaccination is well-tolerated and immunogenic in adults with HIV, with responses improving post-third dose. Anti-spike antibodies serve as a reliable indicator of neutralising activity. Discordances between anti-spike and neutralising responses were accompanied by detectable IFN-γ responses, underlining the complexity of the immune response in this population. [ABSTRACT FROM AUTHOR]

In recent decades, the use of plastic mulch in agriculture has largely increased to meet the growing demand for food. Despite their potential benefits, it is still unknown the long-term impact of mulches on soil microbiome. In this study, we compared at a mesocosm level the effects of polyethylene (Plastic) and Mater-bi® (Bioplastic) mulches on the soil physico-chemical (i.e., pH, soil water content, Fourier transform infrared-attenuated total reflection-FTIR), microbiological, and biochemical (i.e., microbial respiration, enzymatic activities, abundances and composition of bacterial, fungal and microarthropod communities) properties after 6 and 12 months. The analysis of the microbiome revealed an increase in bacterial richness and diversity in the 12-month-treated bioplastic soils. Members of Solirubrobacterales, Vicinamibacterales, Nitrososphaerales, Crenarchaeota, and Clostridiales were the most abundant following the bioplastic treatment. While the fungal and microarthropod communities varied over time, neither of them was affected by the type of mulching. Further longer-term research is needed to clarify the impact of bioplastic and plastic mulches on the soil microbiome, including microarthropods, and its dynamics over time. [ABSTRACT FROM AUTHOR]

One of the critical challenges in the fiber-based packaging industry is to produce low-density paperboards with high functionality and attractive cost structure. In this study, we examine how control of the hierarchical fiber swelling can be used to enhance bonding and generate a low-density fiber network with excellent strength properties. Here, the osmotic pressure inside the cell wall is increased by adding phosphate groups with a deep eutectic solvent (DES) functional drying method. Together with mechanical refining, this process causes the fibril aggregates to split and swell up massively. This effect was measured by a novel thermoporosimetry analysis method. The treated fibers have enhanced external fibrillation, fibrillar fines and bonding potential. When mixed with relatively stiff, unrefined fibers, a well-bonded sheet with lower density than a conventionally refined reference sheet was achieved. The results suggest that pulp fibers can be "nanoengineered" to enhance performance without the complications of producing and adding nanocellulose. [ABSTRACT FROM AUTHOR]

Visceral myopathy is a rare, life-threatening disease linked to identified genetic mutations in 60% of cases. Mostly due to the dearth of knowledge regarding its pathogenesis, effective treatments are lacking. The disease is most commonly diagnosed in children with recurrent or persistent disabling episodes of functional intestinal obstruction, which can be life threatening, often requiring long-term parenteral or specialized enteral nutritional support. Although these interventions are undisputedly life-saving as they allow affected individuals to avoid malnutrition and related complications, they also seriously compromise their quality of life and can carry the risk of sepsis and thrombosis. Animal models for visceral myopathy, which could be crucial for advancing the scientific knowledge of this condition, are scarce. Clearly, a collaborative network is needed to develop research plans to clarify genotype–phenotype correlations and unravel molecular mechanisms to provide targeted therapeutic strategies. This paper represents a summary report of the first 'European Forum on Visceral Myopathy'. This forum was attended by an international interdisciplinary working group that met to better understand visceral myopathy and foster interaction among scientists actively involved in the field and clinicians who specialize in care of people with visceral myopathy. [ABSTRACT FROM AUTHOR]

The purpose of this study is to examine the hornification of enzymatically hydrolyzed high consistency softwood kraft pulp in an experimental defibration dryer. This device dries pulp under turbulent conditions which can prevent interfiber bonding and produce a separated fiber population. This is useful in certain applications, such as composites, which require dry, unbonded pulp fibers. In this study, we examine how fibrillated pulps behave in the dryer with respect to pore expansion in hydrolysis and collapse in drying (hornification). It was found that the endoglucanase cocktail increased the micro-, meso-, and macropore volumes as a function of hydrolysis time. Drying decreased the pore volumes of each size category, with the biggest changes in the macropore region. The pulp with the highest swelling after hydrolysis had the lowest swelling after drying. The mesopores that were formed in hydrolysis were somewhat preserved after drying. After drying, unfibrillated pulp had good fiber separation, while the highly fibrillated samples formed sub-millimeter, spherical particles. [ABSTRACT FROM AUTHOR]

Purpose: With contemporaneous advances in congenital central hypoventilation syndrome (CCHS), recognition, confirmatory diagnostics with PHOX2B genetic testing, and conservative management to reduce the risk of early morbidity and mortality, the prevalence of identified adolescents and young adults with CCHS and later-onset (LO-) CCHS has increased. Accordingly, there is heightened awareness and need for transitional care of these patients from pediatric medicine into a multidisciplinary adult medical team. Hence, this review summarizes key clinical and management considerations for patients with CCHS and LO-CCHS and emphasizes topics of particular importance for this demographic. Methods: We performed a systematic review of literature on diagnostics, pathophysiology, and clinical management in CCHS and LO-CCHS, and supplemented the review with anecdotal but extensive experiences from large academic pediatric centers with expertise in CCHS. Results: We summarized our findings topically for an overview of the medical care in CCHS and LO-CCHS specifically applicable to adolescents and adults. Care topics include genetic and embryologic basis of the disease, clinical presentation, management, variability in autonomic nervous system dysfunction, and clarity regarding transitional care with unique considerations such as living independently, family planning, exposure to anesthesia, and alcohol and drug use. Conclusions: While a lack of experience and evidence exists in the care of adults with CCHS and LO-CCHS, a review of the relevant literature and expert consensus provides guidance for transitional care areas. [ABSTRACT FROM AUTHOR]

Purpose: NLRC4-associated autoinflammatory disease (NLRC4-AID) is an autosomal dominant condition presenting with a range of clinical manifestations which can include macrophage activation syndrome (MAS) and severe enterocolitis. We now report the first homozygous mutation in NLRC4 (c.478G > A, p.A160T) causing autoinflammatory disease with immune dysregulation and find that heterozygous carriers in the general population are at increased risk of developing ulcerative colitis. Methods: Circulating immune cells and inflammatory markers were profiled and historical clinical data interrogated. DNA was extracted and sequenced using standard procedures. Inflammasome activation assays for ASC speck formation, pyroptosis, and IL-1β/IL-18 secretion confirmed pathogenicity of the mutation in vitro. Genome-wide association of NLRC4 (A160T) with ulcerative colitis was examined using data from the IBD exomes portal. Results: A 60-year-old Brazilian female patient was evaluated for recurrent episodes of systemic inflammation from six months of age. Episodes were characterized by recurrent low-grade fever, chills, oral ulceration, uveitis, arthralgia, and abdominal pain, followed by diarrhea with mucus and variable skin rash. High doses of corticosteroids were somewhat effective in controlling disease and anti-IL-1β therapy partially controlled symptoms. While on treatment, serum IL-1β and IL-18 levels remained elevated. Genetic investigations identified a homozygous mutation in NLRC4 (A160T), inherited in a recessive fashion. Increased ASC speck formation and IL-1β/IL-18 secretion confirmed pathogenicity when NLRC4 (A160T) was analyzed in human cell lines. This allele is significantly enriched in patients with ulcerative colitis: OR 2.546 (95% 1.778–3.644), P = 0.01305. Conclusion: NLRC4 (A160T) can either cause recessively inherited autoinflammation and immune dysregulation, or function as a heterozygous risk factor for the development of ulcerative colitis. [ABSTRACT FROM AUTHOR]

Response to ritonavir-boosted-protease inhibitors (PI/r)-based regimen is associated with some Gag mutations among HIV-1 B-clade. There is limited data on Gag mutations and their covariation with mutations in protease among HIV-1 non-B-clades at PI/r-based treatment failure. Thus, we characterized Gag mutations present in isolates from HIV-1 infected individuals treated with a PI/r-regimen (n = 143) and compared them with those obtained from individuals not treated with PI/r (ART-naïve [n = 101] or reverse transcriptase inhibitors (RTI) treated [n = 118]). The most frequent HIV-1 subtypes were CRF02_AG (54.69%), A (13.53%), D (6.35%) and G (4.69%). Eighteen Gag mutations showed a significantly higher prevalence in PI/r-treated isolates compared to ART-naïve (p < 0.05): Group 1 (prevalence < 1% in drug-naïve): L449F, D480N, L483Q, Y484P, T487V; group 2 (prevalence 1–5% in drug-naïve): S462L, I479G, I479K, D480E; group 3 (prevalence ≥ 5% in drug-naïve): P453L, E460A, R464G, S465F, V467E, Q474P, I479R, E482G, T487A. Five Gag mutations (L449F, P453L, D480E, S465F, Y484P) positively correlated (Phi ≥ 0.2, p < 0.05) with protease-resistance mutations. At PI/r-failure, no significant difference was observed between patients with and without these associated Gag mutations in term of viremia or CD4 count. This analysis suggests that some Gag mutations show an increased frequency in patients failing PIs among HIV-1 non-B clades. [ABSTRACT FROM AUTHOR]

Barataria (LA, USA) is an interdistributary deltaic basin that has experienced extensive marsh loss. The fate of these marshes is strongly controlled by the concentration of total suspended sediments (TSS) in the adjacent open bay water. This parameter, however, is poorly constrained, thus limiting the ability to predict the future marsh evolution. Here we investigate the open bay water sediment dynamics using three complementary approaches: monthly field surveys at 37 locations along the bay axis over 22 years, remote sensing over 20 years, and turbidity time series at 5 locations over 4 years. Monthly field sampling and remote sensing reveal that the TSS is highly seasonal and spatially variable. In particular, the sediment delivered through the Gulf Intracoastal Waterway (GIWW) during the flood season (January–April) dominates the TSS signal in mid-Barataria. This sediment originates mainly from the Atchafalaya River and is advected for more than 100 km before reaching Barataria. Because of a hysteresis in sediment transport, the TSS in the river water, and hence in the GIWW, is not uniquely related to the river discharge. As such, late flood season discharges do not contribute much sediment to Barataria. We estimate that the GIWW delivers on average 0.21 Tg of sediment per year to mid-Barataria. A different sediment input is instead present in lower Barataria, where river-borne sediment exiting the "birdfoot" of the Mississippi Delta is advected by easterly winds, especially during spring. At all five stations within Barataria, turbidity time series reveal that the daily sediment dynamics is mainly associated with local wind wave resuspension. River inputs and wave resuspension contribute nearly equally to the yearly averaged TSS, of about 80 mg/l on average. The GIWW, built in the 1920s, is an important but overlooked source of sediments for Barataria that can serve as a present-day analogue for the proposed Mississippi River sediment diversions. [ABSTRACT FROM AUTHOR]

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) have been underestimated in Hirschsprung disease (HSCR). This paper aims at reporting results of patients with HSCR who underwent kidney and urinary tract assessment. Methods: Patients seen between December 2005 and November 2020 underwent a complete kidney and urinary tract diagnostic workup. Data regarding CAKUT, gender, length of aganglionosis, familial history, HSCR-associated enterocolitis (HAEC), RET genotype, and outcome were collected. Results: Out of 472 patients, 280 completed the workup and represented the focus. Male to female ratio was 3.24:1. Familial cases accounted for 9.8% of patients. RET mutations were detected in 19.8%. We encountered a total of 61 patients with 70 nephrological issues (21.8%), including 28 hypoplasia/dysplasia, 12 hydronephrosis, 11 vesicoureteric reflux, 7 duplex collecting system, 2 kidney agenesis, 2 horseshoe kidney, and 8 miscellanea, involving 91 kidneys without side preponderance (50 right, 41 left). Of these 61 patients, 20 (7.1% of the whole series) required medical or surgical treatment. When comparing patients with and without CAKUT, familial history proved to occur with a significantly lower frequency in the former as did better patient perspectives of outcome. Conclusions: We confirmed that all diagnostic workups in HSCR should include a complete kidney and urinary tract diagnostic workup. Our study suggests that genes other than RET could play a role in determining CAKUT. Given worse patient perspectives of outcome, CAKUT seems to significantly interfere with quality of life thus confirming the need for early diagnosis and tailored prevention strategies. [ABSTRACT FROM AUTHOR]

We prove that every expansive continuous action with the weak specification property of an amenable group G on a compact Hausdorff space X has the Myhill property, i.e., every pre-injective continuous self-mapping of X commuting with the action of G on X is surjective. This extends a result previously obtained by Hanfeng Li in the case when X is metrizable. [ABSTRACT FROM AUTHOR]

Male breast cancer (MBC) is a rare disease. The few studies on MBC reported conflicting data regarding survival outcomes compared to women. This study has two objectives: to describe the characteristics of a single-cohort of MBC and to compare overall survival (OS) and disease-free survival (DFS) between men and women using the propensity score matching (PSM) analysis. We considered MBC patients (n = 40) diagnosed between January 2004 and May 2019. Clinical, pathological, oncological and follow-up data were analyzed. Univariate analysis was performed to determine the prognostic factors on OS and DFS for MBC. We selected female patients with BC (n = 2678). To minimize the effect of the imbalance of the prognostic factors between the two cohorts, the PSM method (1:3 ratio) was applied and differences in survival between the two groups were assessed. The average age of MBC patients was 73 years. The 5-year OS and DFS rates were 76.7% and 72.2% respectively. The prognostic factors that significantly influenced OS and DFS were tumor size and lymph node status. After the PSM, 5 year-OS was similar between MBC and FBC (72.9% vs 72.3%, p = 0.70) while we found a worse DFS for MBC (72.2% vs 91.4%, p = 0.03). Our data confirmed previous reported MBC characteristics: we found a higher risk of recurrence in MBC compared to FMC but similar OS. MBC and FMC are different entities and studies are needed to understand its epidemiology and guide its management. [ABSTRACT FROM AUTHOR]

Purpose: Prediction algorithms estimating survival rates for breast cancer (BC) based upon risk factors and treatment could give a help to the clinicians during multidisciplinary meetings. The aim of this study was to evaluate accuracy and clinical utility of three different scores: the Clinical Treatment Score Post-5 Years (CTS5), the PREDICT Score, and the Nottingham Prognostic Index (NPI). Methods: This is a retrospective cohort analysis conducted on prospectively recorded databases of two EUSOMA certified centers (Breast Unit of Trieste Academic Hospital and of Cremona Hospital, Italy). We included patients with Luminal BC undergone to breast surgery between 2010 and 2015, and subsequent endocrine therapy for 5 years for curative intent. Results: A total of 473 patients were enrolled in this study. ROC analysis showed fair accuracy for NPI, good accuracy for PREDICT, and optimal accuracy for CTS5 (AUC 0.7, 0.76, and 0.83, respectively). The three scores seemed strongly correlated in Spearman's rank correlation coefficient analysis. PREDICT partially overestimated OS in patients undergone to mastectomy, and in pT3-4, G3 tumors. Considering DRFS as a surrogate of OS, CTS5 showed women in intermediate and high risk class had shorter OS too (respectively p = 0.001 and p < 0.001). Combining scores does not improve prognostication power. Conclusion: Mathematical models may help clinicians in decision making (adjuvant therapies, CDK4/6i, genomic test's gray zones). CTS5 has the higher prognostic accuracy in predicting recurrence, while score predicting OS did not show substantial advances, proving that pN, G, and pT are still the most important variables in predicting OS. [ABSTRACT FROM AUTHOR]

In recent decades, global oil palm production has shown an abrupt increase, with almost 90% produced in Southeast Asia alone. To understand trends in oil palm plantation expansion and for landscape-level planning, accurate maps are needed. Although different oil palm maps have been produced using remote sensing in the past, here we use Sentinel 1 imagery to generate an oil palm plantation map for Indonesia, Malaysia and Thailand for the year 2017. In addition to location, the age of the oil palm plantation is critical for calculating yields. Here we have used a Landsat time series approach to determine the year in which the oil palm plantations are first detected, at which point they are 2 to 3 years of age. From this, the approximate age of the oil palm plantation in 2017 can be derived. Measurement(s) 2-D extent • age Technology Type(s) Classification Factor Type(s) input dataset Sample Characteristic - Organism Elaeis guineensis Sample Characteristic - Environment oil palm plantation Sample Characteristic - Location Southeast Asia Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13899713 [ABSTRACT FROM AUTHOR]

In this study, sound absorbing materials were produced through foam forming technique using hardwood and softwood pulps with varying chemical composition, ultrastructural, and morphological properties as raw materials. The sound absorption properties of the produced foams were measured and related to the ultrastructure and the morphology of the pulp fibres. All the fibre foams provided sound absorption properties comparable to those of conventional porous materials used for acoustic purposes. In general, further processing, as well as smaller fibre dimensions contribute to improve the sound absorption properties of the pulp fibre foams. The results provide valuable insight on the optimization of wood-based sound absorbing materials. [ABSTRACT FROM AUTHOR]

Forest disturbance regimes are expected to intensify as Earth's climate changes. Quantifying forest vulnerability to disturbances and understanding the underlying mechanisms is crucial to develop mitigation and adaptation strategies. However, observational evidence is largely missing at regional to continental scales. Here, we quantify the vulnerability of European forests to fires, windthrows and insect outbreaks during the period 1979–2018 by integrating machine learning with disturbance data and satellite products. We show that about 33.4 billion tonnes of forest biomass could be seriously affected by these disturbances, with higher relative losses when exposed to windthrows (40%) and fires (34%) compared to insect outbreaks (26%). The spatial pattern in vulnerability is strongly controlled by the interplay between forest characteristics and background climate. Hotspot regions for vulnerability are located at the borders of the climate envelope, in both southern and northern Europe. There is a clear trend in overall forest vulnerability that is driven by a warming-induced reduction in plant defence mechanisms to insect outbreaks, especially at high latitudes. Natural disturbances imperil healthy and productive forests, but quantifying their effects at large scales is challenging. Here the authors apply machine learning to disturbance records and satellite data to quantify and map European forest vulnerability to fires, windthrows, and insect outbreaks through 1979-2018. [ABSTRACT FROM AUTHOR]

Blau syndrome is a rare autosomal dominant monogenic auto-inflammatory disorder characterized by triad of granulomatous polyarthritis, dermatitis, and uveitis. However, it may be difficult to recognize this syndrome in the absence of all three characteristic clinical manifestations. A 3-year-old girl presented with early onset symmetric polyarthritis and developed granulomatous uveitis at 13 years of age. However, Blau syndrome was suspected at 21 years of age when she was diagnosed to have disseminated granulomas in liver and kidneys. Diagnosis of Blau syndrome was confirmed by finding a mutation in NOD2 gene (p.Arg334Gln; FP2678). She was initiated on adalimumab therapy and she showed good response to this treatment. We did a literature search to find out all reported cases of Blau syndrome with disseminated granulomatous inflammation and all cases of Blau syndrome that were treated with adalimumab therapy. Seventeen patients with Blau syndrome have been reported to have granulomas at unusual locations (liver; kidneys; lungs; salivary glands; intestine; and lymph nodes). Adalimumab has been reported to be used in 33 patients with Blau syndrome. The indication to initiate adalimumab in large majority of these patients was persistence of uveitis. A possibility of Blau syndrome should be considered in all children presenting with early onset arthritis (especially with the presence of boggy swelling) and granulomatous uveitis. Granulomas in the liver and kidney are uncommon disease manifestations. Adalimumab may be an effective treatment for patients with Blau syndrome who are resistant to other forms of therapy. [ABSTRACT FROM AUTHOR]

Forests provide a series of ecosystem services that are crucial to our society. In the European Union (EU), forests account for approximately 38% of the total land surface1. These forests are important carbon sinks, and their conservation efforts are vital for the EU's vision of achieving climate neutrality by 20502. However, the increasing demand for forest services and products, driven by the bioeconomy, poses challenges for sustainable forest management. Here we use fine-scale satellite data to observe an increase in the harvested forest area (49 per cent) and an increase in biomass loss (69 per cent) over Europe for the period of 2016–2018 relative to 2011–2015, with large losses occurring on the Iberian Peninsula and in the Nordic and Baltic countries. Satellite imagery further reveals that the average patch size of harvested area increased by 34 per cent across Europe, with potential effects on biodiversity, soil erosion and water regulation. The increase in the rate of forest harvest is the result of the recent expansion of wood markets, as suggested by econometric indicators on forestry, wood-based bioenergy and international trade. If such a high rate of forest harvest continues, the post-2020 EU vision of forest-based climate mitigation may be hampered, and the additional carbon losses from forests would require extra emission reductions in other sectors in order to reach climate neutrality by 20503. Fine-scale satellite data are used to quantify forest harvest rates in 26 European countries, finding an increase in harvested forest area of 49% and an increase in biomass loss of 69% between 2011–2015 and 2016–2018. [ABSTRACT FROM AUTHOR]

Recent years have witnessed an increasing interest in man-made cellulosic fibers, whose production generally requires cellulose dissolution and regeneration. Cellulosic fibers are difficult to dissolve. Thus, the recalcitrance of wood pulp can be an estimate of its reactivity. Pulp reactivity is usually assessed via complex and time-consuming laboratory simulations of the viscose process. This study proposes a faster and more convenient approach. The dissolution-based torque reactivity (DTR) test measures the evolution of the rheological properties of a pulp suspension under dissolution in cupriethylenediamine. Reactivity is quantified in terms of initial dissolution rates (IDR) and dissolution times (DT). This study describes the measurement protocol for the DTR test and its application to some commercial pulps and a series of pulps hornified to different extents. The IDR and DT values were compared with other pulp features, including degree of polymerization, molecular weight distribution, specific surface area and water retention value. The DTR test proved to be reasonably precise and fast to carry out. [ABSTRACT FROM AUTHOR]

Background: There are currently few data concerning the cerebrospinal fluid (CSF) penetration of daptomycin in patients with healthcare-associated meningitis. This study aims (1) to better characterize the pharmacokinetics of daptomycin in humans during a 7-day intravenous (IV) therapy course, and (2) to study the penetration of daptomycin in the CSF after IV infusion at the dose of 10 mg/kg.Results: In this prospective observational study, we enrolled nine patients with an implanted external ventricular drainage and a diagnosis of a healthcare-associated meningitis. Daptomycin was administered at 10 mg/kg for a maximum of 7 days. The pharmacokinetic of daptomycin was studied using a two-compartment population/pharmacokinetic (POP/PK) model and by means of a nonlinear mixed effects modeling approach. A large inter-individual variability in plasma area under the curve (Range: 574.7-1366.3 h mg/L), paralleled by high-peak plasma concentration (Cmax) (all values > 60 mg/L), was noted. The inter-individual variability of CSF-AUC although significant (range: 1.17-6.81 h mg/L) was narrower than previously reported and with a late occurrence of CSF-Cmax (range: 6.04-9.54 h). The terminal half-life between plasma and CSF was similar. tmax values in CSF did not show a high inter-individual variability, and the fluctuations of predicted CSF concentrations were minimal. The mean value for daptomycin penetration obtained from our model was 0.45%.Conclusions: Our POP/PK model was able to describe the pharmacokinetics of daptomycin in both plasma and CSF, showing that daptomycin (up to 7 days at 10 mg/kg) has minimal penetration into central nervous system. Furthermore, the observed variability of AUC, tmax and predicted concentration in CSF was lower than what previously reported in the literature. Based on the present findings, it is unlikely that daptomycin could reach CSF concentrations high enough to have clinical efficacy; this should be tested in future studies. [ABSTRACT FROM AUTHOR]

The origins of the unique properties of natural fibres have remained largely unresolved because of the complex interrelations between structural hierarchy, chirality and bound water. In this paper, analysis of the melting endotherms for bleached hardwood pulps indicates that the amount of non-freezing bound water (0.21 g/g) is roughly half of the amount of freezing bound water (0.42 g/g). We link this result to the two smallest constitutive units, microfibrils and their bundles, using molecular dynamics simulations at both hierarchical levels. The molecular water layers found in the simulations correspond quite accurately to the measured amount of non-freezing and freezing bound water. Disorder that results from the microfibril twist and amphiphilicity prevents co-crystallisation, leaving routes for water molecules to diffuse inside the microfibril bundle. Moreover, the simulations predict correctly the magnitude of the right-handed twist at different hierarchical levels. Significant changes in hydroxymethyl group conformations are seen during twisting that compare well with existing experimental data. Our findings go beyond earlier modelling studies in predicting the twist and structure of the microfibril bundle. [ABSTRACT FROM AUTHOR]

Let Γ be a countable Abelian group and f ∈ Z [ Γ ] , where Z [ Γ ] denotes the integral group ring of Γ . Consider the Pontryagin dual Xf of the cyclic Z [ Γ ] -module Z [ Γ ] / Z [ Γ ] f and suppose that f is weakly expansive (e.g., f is invertible in ℓ 1 (Γ) , or, when Γ is not virtually Z or Z 2 , f is well-balanced) and that Xf is connected. We prove that if τ : X f → X f is a Γ -equivariant continuous map, then τ is surjective if and only if the restriction of τ to each Γ -homoclinicity class is injective. We also show that this equivalence remains valid in the case when Γ = Z d and f ∈ Z [ Γ ] = Z [ u 1 , u 1 - 1 , ... , u d , u d - 1 ] is an irreducible atoral polynomial whose zero-set Z(f) satisfies some suitable finiteness conditions (e.g., when d ≥ 2 such that Z(f) is finite). These two results are analogues of the classical Garden of Eden theorem of Moore and Myhill for cellular automata with finite alphabet over Γ . [ABSTRACT FROM AUTHOR]

Integrase-strand-transfer inhibitors (INSTIs) are known to rapidly reduce HIV-1 plasma viral load, replication cycles, and new viral integrations, thus potentially limiting viral evolution. Here, we assessed the role of INSTIs on HIV-1 V3 evolution in a cohort of 89 HIV-1-infected individuals starting an INSTI- (N = 41, [dolutegravir: N = 1; elvitegravir: N = 3; raltegravir: N = 37]) or a non-INSTI-based (N = 48) combined antiretroviral therapy (cART), with two plasma RNA V3 genotypic tests available (one before [baseline] and one during cART). V3 sequences were analysed for genetic distance (Tajima-Nei model) and positive selection (dN/dS ratio). Individuals were mainly infected by B subtype (71.9%). Median (interquartile-range, IQR) plasma viral load and CD4 + T cell count at baseline were 4.8 (3.5–5.5) log10 copies/mL and 207 (67–441) cells/mm3, respectively. Genetic distance (median, IQR) between the V3 sequences obtained during cART and those obtained at baseline was 0.04 (0.01–0.07). By considering treatment, genetic distance was significantly lower in INSTI-treated than in non-INSTI-treated individuals (median [IQR]: 0.03[0.01–0.04] vs. 0.05[0.02–0.08], p = 0.026). In line with this, a positive selection (defined as dN/dS ≥ 1) was observed in 36.6% of V3 sequences belonging to the INSTI-treated group and in 56.3% of non-INSTI group (p = 0.05). Multivariable logistic regression confirmed the independent correlation of INSTI-based regimens with a lower probability of both V3 evolution (adjusted odds-ratio: 0.35 [confidence interval (CI) 0.13–0.88], p = 0.027) and positive selection (even if with a trend) (adjusted odds-ratio: 0.46 [CI 0.19–1.11], p = 0.083). Overall, this study suggests a role of INSTI-based regimen in limiting HIV-1 V3 evolution over time. Further studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Enzymatic modification of bleached softwood kraft fibres for improved fibre reactivity was studied at high (20% w/w) and low (1% w/w) dry matter content. The role of enzyme family and structure in fibre modification was assessed using endoglucanases from three structurally different glycoside hydrolase (GH) families (5, 7 and 45) with and without a carbohydrate binding module (CBM). Based on the amount of dissolved sugars, enzyme action at high consistency was about sixfold higher compared to a fibre treatment at low consistency. The GH45 endoglucanase was found to be most specific in acting on pulp cellulose whereas the family 5 and 7 endoglucanases had activity also on pulp hemicelluloses. The GH45 endoglucanase was found to be most efficient in reducing molecular weight and viscosity of the pulp. In addition, treatment with the GH45 endoglucanase resulted in the highest micropore volume in fibres and thus an increase in cellulose accessibility. The increased accessibility could be seen as decreased dissolution time in cupriethylenediamine using recently developed analytical techniques: viscometric analysis and microscopic video analysis. At high consistency, CBM was not promoting enzyme action, although CBMs are known to be beneficial at low dry matter conditions. [ABSTRACT FROM AUTHOR]

The biology of HIV is rather complex due to high rate of replication, frequent recombination, and introduction of mutations. This gives rise to a number of distinct variants referred as quasispecies. In addition, the latency within reservoir allows the periodic reactivation of virus replication. The rapid replication of HIV allows immune response escape and establishment of resistance to therapy that can be acquired through drug selection and/or transmitted among individuals. This prompted, over the years, the development of a range of assays aimed to determine drug resistance and sensitivity, to be used both in clinical practice and in antiviral research. Reverse transcriptase (RT) inhibitors have an eminent place among the anti-HIV drugs, being constantly present from the beginning until today in the most commonly used antiviral regimens. This mini-review seeks to provide an up-to-date overview of recent efforts in developing even more reliable and simple methods, of both genotypic and phenotypic types, for specifically detecting drug resistance and sensitivity to RT inhibitors. [ABSTRACT FROM AUTHOR]

Direct-acting antivirals (DAAs) for the treatment of HCV have dramatically increased the rate of sustained virological response: patients not achieving sustained virological response represent a challenge and rates of late recurrent viremia are very low. We describe here the first case of a very late HCV relapse, following an atypical kinetics (characterized by a spontaneous but transient HCV clearance after an early virological relapse), in a HIV co-infected patient treated with DAAs. Optimal adherence to the therapy was well documented and a phylogenetic analysis ruled out a possible reinfection from a different HCV strain. In conclusion, our case underlines the importance of a long follow-up (> 48 weeks) after DAAs therapies in HCV-HIV co-infected patients who might benefit the most from a very rigorous virological surveillance. [ABSTRACT FROM AUTHOR]

To evaluate incidence rates of and predictors for any antiretroviral (ART) drug discontinuation by HCV infection status in a large Italian cohort of HIV infected patients. All patients enrolled in ICONA who started combination antiretroviral therapy (cART) containing abacavir or tenofovir or emtricitabine or lamivudine plus efavirenz or rilpivirine or atazanavir/r or darunavir/r (DRV/r) or lopinavir/r or dolutegravir or elvitegravir or raltegravir were included. Multivariate Poisson regression models were used to determine factors independently associated with single ART drug discontinuation. Inverse probability weighting method to control for potential informative censoring was applied. Data from 10,637 patients were analyzed and 1,030 (9.7%) were HCV-Ab positive. Overall, there were 15,464 ART discontinuations due to any reason in 82,415.9 person-years of follow-up (PYFU) for an incidence rate (IR) of 18.8 (95% confidence interval [95%CI] 18.5-19.1) per 100 PYFU. No difference in IR of ART discontinuation due to any reason between HCV-infected and -uninfected patients was found. In a multivariable Poisson regression model, HCV-infected participants were at higher risk of darunavir/r discontinuation due to any reason (adjusted incidence rate ratio = 1.5, 95%CI 1.01-2.22, p value = 0.045) independently of demographics, HIV-related, ART and life-style factors. Among DRV/r treated patients, we found that HCV-viremic patients had twice the risk of ART discontinuation due to any reason than HCV-aviremic patients. In conclusion, HIV/HCV coinfected patients had a marginal risk increase of DRV/r discontinuation due to any reason compared with those without coinfection. [ABSTRACT FROM AUTHOR]

Purpose: The present study was aimed at investigating whether imatinib pharmacogenetics is related to its pharmacodynamics in patients affected by chronic myeloid leukemia.Methods: Through a procedure based on a sequence of classical statistics methods, we investigated the possible relationships between treatment efficacy/tolerability and combinations of time-independent variables as gender and genetic covariates in the form of single nucleotide polymorphisms (SNPs) or combinations thereof. Moreover, since the drug tolerability has a strong incidence on the discontinuation of the therapy, we investigated whether the time of manifestation of the most frequent toxic effects can be related to time-independent patients' characteristics or not.Results: We found that a combination of two polymorphisms, namely hOCT1 c.480C>G (rs683369) and ABCB1 c.3435C>T (rs1045642), seems to play the role of predictor for imatinib in both efficacy and toxicity. Furthermore, the time of manifestation of edema toxicity is found to be associated to a combination of gender and ABCB1 c.3435C>T, whereas the time of manifestation of cramp toxicity appears related to gender.Conclusions: The novelty of this study is dual: the achievement of results that potentially have a significant clinical interest and the demonstration that the adoption of composed covariates may represent a unique tool to study different aspects of the treatment with imatinib. [ABSTRACT FROM AUTHOR]

Purpose: Abdominal aortic aneurysm (AAA) accompanied by common iliac artery (CIA) aneurysms requires a more demanding procedure owing to the difficulties in obtaining an adequate distal landing zone for the stent-graft limb(s), a potential site of endoleak. The "sandwich technique" is a procedure to increase EVAR feasibility in the setting of adverse or challenging CIA anatomy. Its main advantages include no restrictions in terms of CIA diameter or length or internal iliac artery (IIA) diameter, no need to wait for a specific stent-graft. Our purpose is to describe our single-center experience and one year follow-up results of this new procedure. Materials and Methods: From April 2009 to June 2010, the sandwich technique was performed in our institution in 7 patients treated for AAA and unilateral CIA aneurysms (n. 5) or bilateral CIA aneurysms (n. 2). Inclusion criteria were the presence of unilateral or bilateral CIA aneurysm (independently from its diameter), IIA artery measuring up to 9 mm in its maximum diameter, not dilatation of IIA and EIA. Results: The mean follow-up length was 15 months (range: 14-20 months). All stent-implanted iliac branches remained patent on 1 year follow-up and IIA flow was preserved. None of the patients had symptoms of pelvic ischemia. CT scan follow-up showed aneurysm shrinkage in five patients, without any sign of endoleaks in all cases. Conclusions: In selected cases, the "sandwich technique" showed good outcomes confirming to be a safe and easy to perform way to overcome anatomical constraints and expanding the limits of EVAR. [ABSTRACT FROM AUTHOR]

Alexander disease is an hereditary leukodystrophy related to mutations of GFAP. Classically AxD was divided in infantile, juvenile, and adult subgroups. Recent data suggested considering only two subtypes: type I (infantile onset with lesions extending to the cerebral hemispheres); type II (adult onset with primary involvement of subtentorial structures). We report two related and one unrelated patients presenting with a peculiar association of clinical and neuroradiological features. GFAP analysis disclosed the presence of one novel and two previously reported mutations. Our patients underline the importance of considering AxD in patients with bulbar symptoms and autonomic dysfunction even if MRI shows only posterior fossa abnormalities, supporting the hypothesis of a third type of AxD sharing features of both type I and type II. The evidence of an intrafamilial phenotypic variability suggests the possible role of still unknown factors influencing the effect of GFAP mutation and determining the phenotype. [ABSTRACT FROM AUTHOR]

We studied the molecular diversity of β-glucosidase-encoding genes, microbial biomass, cellulase, N-acetyl-glucosaminidase, β-glucosidase, and β-galactosidase activities in the rhizosphere and bulk soil of two maize lines differing in nitrogen use efficiency (NUE). The maize lines had significant differences in diversity of β-glucosidase-encoding genes in their rhizosphere, and Actinobacteria and Proteobacteria were the dominating phyla in all samples, but representatives of Bacteroidetes, Chloroflexi, Deinococcus- Thermus, Firmicutes, and Cyanobacteria were also detected. Among the Proteobacteria, β-glucosidase genes from α-, β-, and γ-Proteobacteria were dominant in the rhizosphere of the high NUE maize line, whereas δ- Proteobacteria β-glucosidase genes were dominant in the rhizosphere of the low NUE maize line. The high NUE maize line also showed higher glucosidase activities in the rhizosphere than the low NUE maize line. We concluded that plants with high NUE select bacterial communities in the rhizosphere differing in the diversity of β-glucosidase-encoding genes which likely result in higher C-hydrolyzing enzyme activities. These effects on the diversity of β-glucosidase-encoding genes may influence the C dynamics in the agro-ecosystems. [ABSTRACT FROM AUTHOR]

The aim of the present paper is to expose two contributions of Mackey, together with a more recent result of Kawanaka and Matsuyama, generalized by Bump and Ginzburg, on the representation theory of a finite group equipped with an involutory anti-automorphism (e.g. the anti-automorphism $${g \mapsto g^{-1}}$$ ). Mackey's first contribution is a detailed version of the so-called Gelfand criterion for weakly symmetric Gelfand pairs. Mackey's second contribution is a characterization of simply reducible groups (a notion introduced by Wigner). The other result is a twisted version of the Frobenius-Schur theorem, where 'twisted' refers to the above-mentioned involutory anti-automorphism. [ABSTRACT FROM AUTHOR]

We performed a longitudinal study (repeated observations of the same sample over time) to investigate both the composition and structure of temporal changes of bacterial community composition in soil mesocosms, subjected to three different treatments (water and 5 or 25 mg kg of dried soil Cd). By analogy with the pan genome concept, we identified a core bacteriome and an accessory bacteriome. Resident taxa were assigned to the core bacteriome, while occasional taxa were assigned to the accessory bacteriome. Core and accessory bacteriome represented roughly 35 and 50 % of the taxa detected, respectively, and were characterized by different taxonomic signatures from phylum to genus level while 15 % of the taxa were found to be unique to a particular sample. In particular, the core bacteriome was characterized by higher abundance of members of Planctomycetes, Actinobacteria, Verrucomicrobia and Acidobacteria, while the accessory bacteriome included more members of Firmicutes, Clamydiae and Proteobacteria, suggesting potentially different responses to environmental changes of members from these phyla. We conclude that the pan-bacteriome model may be a useful approach to gain insight for modeling bacterial community structure and inferring different abilities of bacteria taxa. [ABSTRACT FROM AUTHOR]