Residual biomasses at scale: Ensuring future bioeconomy uses outperform current baseline.

To shift towards low-fossil carbon economies, making more out of residual biomass is increasingly promoted. Yet, it remains unclear if implementing advanced technologies to reuse these streams really achieves net environmental benefits compared to current management practices. By integrating spatially-explicit resource flow analysis, consequential life cycle assessment (LCA), and uncertainty analysis, we propose a single framework to quantify the residual biomass environmental baseline of a territory, and apply it to the case of France. The output is the environmental threshold that a future large-scale territorial bioeconomy strategy should overpass. For France, we estimate the residual biomass baseline to generate 18.4 ±â€¯2.7 MtCO2-eq·y-1 (climate change), 255 ±â€¯35 ktN-eq·y-1 (marine eutrophication), and 12,300 ±â€¯800 disease incidences per year (particulate matter formation). The current use of crop residues and livestock effluents, being essentially a return to arable lands, was found to represent more than 90 % of total environmental impacts and uncertainties, uncovering a need for more certain data. At present, utilizing residual streams as organic fertilizers fulfills over half of France's total phosphorus (P) and potassium (K) demands. However, it only meets 6 % of the nitrogen demand, primarily because nitrogen is lost through air and water. This, coupled with the overall territorial diagnosis, led us to revisit the idea of using the current situation (based on 2018 data) as a baseline for future bioeconomy trajectories. We suggest that these should rather be compared to a projected baseline accounting for ongoing basic mitigation efforts, estimated for France at 8.5 MtCO2-eq·y-1.

Upgrading agrifood co-products via solid fermentation yields environmental benefits under specific conditions only.

Transforming residual biomass into edible ingredients is increasingly promoted to alleviate the environmental impacts of food systems. Yet, these approaches mostly rely on emerging technologies and constrained resources, and their environmental benefits remain unclear. By combining process-based consequential life cycle analysis, uncertainty assessment and biomass resource estimation, we quantified the impacts of deploying waste-to-nutrition pathways, here applied to the upgrading of agrifood co-products by solid-state fermentation (SSF). The benefits of reducing the demand for soybean meal by enhancing the protein concentration of feed through SSF do not compensate for the environmental burdens induced by the process on climate change, water depletion and land use. Besides unlocking feed markets to low-feed-quality streams, SSF outperforms energy valorization for most environmental impacts but is less competitive to mitigate climate change. Yet, SSF yields overall environmental benefits when unlocking food markets rather than supplying feed and energy services. Systematic methodological harmonization is required to assess the potential of novel ingredients, as outcomes vary according to the displaced food and feed baskets, and related land use changes.

Waste-to-nutrition: a review of current and emerging conversion pathways.

Residual biomass is acknowledged as a key sustainable feedstock for the transition towards circular and low fossil carbon economies to supply whether energy, chemical, material and food products or services. The latter is receiving increasing attention, in particular in the perspective of decoupling nutrition from arable land demand. In order to provide a comprehensive overview of the technical possibilities to convert residual biomasses into edible ingredients, we reviewed over 950 scientific and industrial records documenting existing and emerging waste-to-nutrition pathways, involving over 150 different feedstocks here grouped under 10 umbrella categories: (i) wood-related residual biomass, (ii) primary crop residues, (iii) manure, (iv) food waste, (v) sludge and wastewater, (vi) green residual biomass, (vii) slaughterhouse by-products, (viii) agrifood co-products, (ix) C1 gases and (x) others. The review includes a detailed description of these pathways, as well as the processes they involve. As a result, we proposed four generic building blocks to systematize waste-to-nutrition conversion sequence patterns, namely enhancement, cracking, extraction and bioconversion. We further introduce a multidimensional representation of the biomasses suitability as potential as nutritional sources according to (i) their content in anti-nutritional compounds, (ii) their degree of structural complexity and (iii) their concentration of macro- and micronutrients. Finally, we suggest that the different pathways can be grouped into eight large families of approaches: (i) insect biorefinery, (ii) green biorefinery, (iii) lignocellulosic biorefinery, (iv) non-soluble protein recovery, (v) gas-intermediate biorefinery, (vi) liquid substrate alternative, (vii) solid-substrate fermentation and (viii) more-out-of-slaughterhouse by-products. The proposed framework aims to support future research in waste recovery and valorization within food systems, along with stimulating reflections on the improvement of resources' cascading use.

Modifications of the endosomal compartment in peripheral blood mononuclear cells and fibroblasts from Alzheimer's disease patients.

Identification of blood-based biomarkers of Alzheimer's disease (AD) remains a challenge. Neuropathological studies have identified enlarged endosomes in post-mortem brains as the earliest cellular change associated to AD. Here the presence of enlarged endosomes was investigated in peripheral blood mononuclear cells from 48 biologically defined AD patients (25 with mild cognitive impairment and 23 with dementia (AD-D)), and 23 age-matched healthy controls using immunocytochemistry and confocal microscopy. The volume and number of endosomes were not significantly different between AD and controls. However, the percentage of cells containing enlarged endosomes was significantly higher in the AD-D group as compared with controls. Furthermore, endosomal volumes significantly correlated to [C(11)]PiB cortical index measured by positron emission tomography in the AD group, independently of the APOE genotype, but not to the levels of amyloid-beta, tau and phosphorylated tau measured in the cerebrospinal fluid. Importantly, we confirmed the presence of enlarged endosomes in fibroblasts from six unrelated AD-D patients as compared with five cognitively normal controls. This study is the first, to our knowledge, to report morphological alterations of the endosomal compartment in peripheral cells from AD patients correlated to amyloid load that will now be evaluated as a possible biomarker.

Plasma DYRK1A as a novel risk factor for Alzheimer's disease.

To determine whether apparent involvement of DYRK1A in Alzheimer's disease (AD) pathology makes it a candidate plasma biomarker for diagnosis, we developed a method to quantify plasma DYRK1A by immunoblot in transgenic mouse models having different gene dosages of Dyrk1a, and, consequently, different relative protein expression. Then, we measured plasma DYRK1A levels in 26 patients with biologically confirmed AD and 25 controls (negative amyloid imaging available on 13). DYRK1A was detected in transgenic mouse brain and plasma samples, and relative levels of DYRK1A correlated with the gene copy number. In plasma from AD patients, DYRK1A levels were significantly lower compared with controls (P<0.0001). Results were similar when we compared AD patients with the subgroup of controls confirmed by negative amyloid imaging. In a subgroup of patients with early AD (CDR=0.5), lower DYRK1A expression was confirmed. In contrast, no difference was found in levels of DYRK1B, the closest relative of DYRK1A, between AD patients and controls. Further, AD patients exhibited a positive correlation between plasma DYRK1A levels and cerebrospinal fluid tau and phosphorylated-tau proteins, but no correlation with amyloid-ß42 levels and Pittsburgh compound B cortical binding. DYRK1A levels detected in lymphoblastoid cell lines from AD patients were also lower when compared with cells from age-matched controls. These findings suggest that reduced DYRK1A expression might be a novel plasma risk factor for AD.

Magnetic resonance imaging for diagnosis of early Alzheimer's disease.

A major challenge for neuroimaging is to contribute to the early diagnosis of Alzheimer's disease (AD). In particular, magnetic resonance imaging (MRI) allows detecting different types of structural and functional abnormalities at an early stage of the disease. Anatomical MRI is the most widely used technique and provides local and global measures of atrophy. The recent diagnostic criteria of "mild cognitive impairment due to AD" include hippocampal atrophy, which is considered a marker of neuronal injury. Advanced image analysis techniques generate automatic and reproducible measures both in the hippocampus and throughout the whole brain. Recent modalities such as diffusion-tensor imaging and resting-state functional MRI provide additional measures that could contribute to the early diagnosis but require further validation.

[Necrotizing autoimmune myopathies]. / Les myopathies nécrosantes auto-immunes.

Necrotizing autoimmune myopathies are included in the spectrum of inflammatory myopathies, together with polymyosis, dermatopolymyosis and inclusion body myositis, despite the characteristic feature of marked muscular necrosis without inflammatory infiltrates. The clinical presentation is highly variable, often similar to the other inflammatory myopathies. The most common finding is nevertheless the severe form with rhabdomyolysis. The creatine kinase level is elevated (around 10,000IU/l) and electromyography shows myopathic changes with increased spontaneous activities reflecting the importance of the muscular necrosis. Muscle biopsy is required for diagnosis, revealing active necrosis of the muscle fibers without inflammatory invasion by CDA+ or CD8+ T-cells. Deposition of a microvascular membrane attack complex (C5b9) is often noted, whereas the upregulation of MHC class 1 is rarely detected. Signs of endomysial microangiopathy are frequently reported. Necrotizing autoimmune myopathies can be associated with antisignal recognition particle (SRP) antibodies or more rarely with the usual inflammatory myopathy antibodies. Paraneoplasic forms are described but remain exceptional. Lastly, necrotizing autoimmune myopathies, sometimes associated with statin therapy, have been recently described. They are linked with an antibody directed against 3-hydroxy-3-methyglutaryl-coenzyme A. Treatment is based on corticosteroid therapy, immunosuppressive drugs or intravenous immunoglobulins. Response is variable, depending on the clinical form.

Major ABO-incompatible BMT: isohemagglutinin reduction with plasma exchange is safe and avoids graft manipulation.

The impact of donor-recipient ABO incompatibility on long-term BMT outcomes remains controversial. A common strategy is to deplete the donor marrow of red cells, although this variably reduces the number of CD34+ cells. This 10-year retrospective study assessed the impact of recipient plasma exchange in major ABO-incompatible allogeneic BMT on outcomes and survival. Target Ab titres were ≤ 1:4 for anti-A and ≤ 1:8 for anti-B. Patients with higher titres underwent plasma exchange before marrow infusion. Of 133 patients who underwent allogeneic BMT, 34 had a major ABO-incompatible donor. The median number of exchanges was 2 (range 1-4). There were no acute haemolytic transfusion reactions. Engraftment times, transfusion requirements and acute and chronic GVHD were no different from those of patients with an ABO-identical donor. Treatment-related mortality at 100 days was 21% in the group with a major ABO-incompatible donor and 17% in the group with an identical donor (P=0.8). Plasma exchange of the recipient is a safe method of managing donor-recipient major ABO incompatibility before BMT without the risk of haematopoietic progenitor cell loss associated with red cell depletion of the graft.

Comparing environmental consequences of anaerobic mono- and co-digestion of pig manure to produce bio-energy--a life cycle perspective.

The aim of this work was to assess the environmental consequences of anaerobic mono- and co-digestion of pig manure to produce bio-energy, from a life cycle perspective. This included assessing environmental impacts and land use change emissions (LUC) required to replace used co-substrates for anaerobic digestion. Environmental impact categories considered were climate change, terrestrial acidification, marine and freshwater eutrophication, particulate matter formation, land use, and fossil fuel depletion. Six scenarios were evaluated: mono-digestion of manure, co-digestion with: maize silage, maize silage and glycerin, beet tails, wheat yeast concentrate (WYC), and roadside grass. Mono-digestion reduced most impacts, but represented a limited source for bio-energy. Co-digestion with maize silage, beet tails, and WYC (competing with animal feed), and glycerin increased bio-energy production (up to 568%), but at expense of increasing climate change (through LUC), marine eutrophication, and land use. Co-digestion with wastes or residues like roadside grass gave the best environmental performance.

A randomized trial of granulocyte colony-stimulating factor (Neupogen) starting day 1 vs day 7 post-autologous stem cell transplantation.

The purpose of the study was to evaluate the effect of delayed granulocyte colony-stimulating factor (G-CSF) use on hematopoietic recovery post-autologous peripheral blood progenitor cell (PBPC) transplantation. Patients were randomized to begin G-CSF on day +1 or day +7 post transplantation. Thirty-seven patients with lymphoma or myeloma undergoing high-dose therapy and autologous PBPC rescue were randomized to daily subcutaneous G-CSF beginning on day +1 or day +7 post-transplant. Patients < or =70 kg received 300 microg/day and >70 kg 480 microg/day. All patients were reinfused with PBPCs with a CD34+ cell count >2.0 x 10(6)/kg. Baseline characteristics of age, sex and CD34+ cell count were similar between the two arms, the median CD34+ cell count being 5.87 x 10(6)/kg in the day +1 group and 7.70 x 10(6)/kg in the day +7 group (P=0.7). The median time to reach a neutrophil count of >0.5 x 10(9)/l was 9 days in the day +1 arm and 10 days in the day +7 arm, a difference which was not statistically significant (P=0.68). Similarly, there was no difference in median days to platelet recovery >20000 x 10(9)/l, which was 10 days in the day +1 arm and 11 days in the day +7 arm (P=0.83). There was also no significant difference in the median duration of febrile neutropenia (4 vs 6 days; P=0.7), intravenous antibiotic use (7 vs 8 days; P=0.54) or median number of red blood cell transfusions (4 vs 7 units; P=0.82) between the two arms. Median length of hospital stay was 11 days post-PBPC reinfusion in both groups. The median number of G-CSF injections used was 8 in the day +1 group and 3 in the day +7 group (P < 0.0001). There is no significant difference in time to neutrophil or platelet recovery when G-CSF is initiated on day +7 compared to day +1 post-autologous PBPC transplantation. There is also no difference in number of febrile neutropenic or antibiotic days, number of red blood cell transfusions or length of hospital stay. The number of doses of G-CSF used per transplant is significantly reduced with delayed initiation, resulting in a significant reduction in drug costs. For patients with an adequately mobilized PBPC graft, the initiation of G-CSF can be delayed until day +7 post-PBPC reinfusion.

Intestinal M3 antigen, a marker for the intestinal-type differentiation of gastric carcinomas.

The mucus-associated intestinal M3 antigen, normally restricted to intestinal goblet cells, was found in 35 out of 100 gastric adenocarcinomas belonging to intestinal (19/64) as well as diffuse (16/36) types according to Laurén's classification. often accompanying the other mucus-associated gastric M1 and M2 antigens. This M3 antigen was predominant over the gastric M antigens in 25 of these 35 tumors; 18 of these belonged to the histological intestinal type. According to the WHO classification, the M3 antigen was found to predominate in all mucinous adenocarcinomas (7/7), was never present in the undifferentiated carcinomas (0/8), but was also found in some tubulo-papillar (16/57) and signet-ring cell (12/27) adenocarcinomas. This antigen could be used as a new criterion and incorporated into a point system containing morphological and tumor cell behavioral considerations; then it would appear to be a good marker for intestinal-type differentiation. Indeed, 22 of these 25 gastric adenocarcinomas which produced predominantly M3 antigen showed such an intestinal-like differentiation. The M antigen pattern of gastric carcinoma suggested a duodenal rather than colonic-type differentiation.