Surgery in the elderly patients with cancer.

With an increasing aging population, there will be a greater need for cancer evaluation and treatment in older patients. Age alone is not a good predictor of postoperative morbidity, and a multidisciplinary approach is crucial for managing comorbidities. Preoperative optimisation, such as prehabilitation, may in some cases reduce postoperative complications, and minimal invasive techniques should be preferred whenever possible. In general, as summarised in this review, cancer treatment in older patients should be individualised based on comorbidities and life expectancy.

Toward scalable biocatalytic conversion of 5-hydroxymethylfurfural by galactose oxidase using coordinated reaction and enzyme engineering.

5-Hydroxymethylfurfural (HMF) has emerged as a crucial bio-based chemical building block in the drive towards developing materials from renewable resources, due to its direct preparation from sugars and its readily diversifiable scaffold. A key obstacle in transitioning to bio-based plastic production lies in meeting the necessary industrial production efficiency, particularly in the cost-effective conversion of HMF to valuable intermediates. Toward addressing the challenge of developing scalable technology for oxidizing crude HMF to more valuable chemicals, here we report coordinated reaction and enzyme engineering to provide a galactose oxidase (GOase) variant with remarkably high activity toward HMF, improved O2 binding and excellent productivity (>1,000,000 TTN). The biocatalyst and reaction conditions presented here for GOase catalysed selective oxidation of HMF to 2,5-diformylfuran offers a productive blueprint for further development, giving hope for the creation of a biocatalytic route to scalable production of furan-based chemical building blocks from sustainable feedstocks.

Fecal microbiota transplantation in hepatic encephalopathy: a systematic review.

Hepatic encephalopathy (HE) is a reversible neurocognitive dysfunction that ranges in severity from subclinical alterations to coma. Patients with chronic liver disease are predisposed to HE due to metabolic failure and portosystemic shunting of toxins, of which ammonia is believed to be the main toxic chemical. Fecal microbiota transplantation (FMT) may reduce ammonia synthesis by altering the gut microbiota composition to a taxon low in urease, diminish uptake of ammonia by reestablishing the integrity of the intestinal barrier and increase ammonia clearance by improving liver function. In this systematic review, we summarize the insights of the current literature examining FMT as a treatment for HE.PubMed and EMBASE were searched on 08 February 2021 using the MeSH terms 'fecal microbiota transplantation & hepatic encephalopathy' and the abbreviations 'FMT & HE'.Eight studies fulfilled our inclusion criteria, comprising two randomized clinical trials, three case reports and three rodent studies. Thirty-nine patients with HE were treated with FMT. Thirty-nine rodents received FMT in laboratory tests. FMT improved neurocognitive test results in four human studies and two rodent studies. Microbiota originating from donors was found in human recipients one year post-FMT. Readmission of patients was lower after treatment with FMT compared to standard of care.FMT may improve neurocognitive function and reduce serious adverse events in patients with HE, but the studies conducted so far have been small and their long-term follow-up is limited. Large-scale, randomized and controlled trials are needed to validate and help standardize the clinical application of FMT in cases of HE.

The Dat Project, an open and decentralized research data tool.

Today's scientific data are primarily stored and accessed via centralized Web-based infrastructure. Centralization has advantages but also carries risks such as link rot and content drift, which can hinder scientific progress. It is time to ask whether traditional, centralized Web architecture aligns with scholarly priorities and values, and to collaboratively move towards new approaches that do.

Cognitive Metaphor Theory and the Metaphysics of Immediacy.

One of the core tenets of cognitive metaphor theory is the claim that metaphors ground abstract knowledge in concrete, first-hand experience. In this paper, I argue that this grounding hypothesis contains some problematic conceptual ambiguities and, under many reasonable interpretations, empirical difficulties. I present evidence that there are foundational obstacles to defining a coherent and cognitively valid concept of "metaphor" and "concrete meaning," and some general problems with singling out certain domains of experience as more immediate than others. I conclude from these considerations that whatever the facts are about the comprehension of individual metaphors, the available evidence is incompatible with the notion of an underlying conceptual structure organized according to the immediacy of experience.

Ecosystem properties of semiarid savanna grassland in West Africa and its relationship with environmental variability.

The Dahra field site in Senegal, West Africa, was established in 2002 to monitor ecosystem properties of semiarid savanna grassland and their responses to climatic and environmental change. This article describes the environment and the ecosystem properties of the site using a unique set of in situ data. The studied variables include hydroclimatic variables, species composition, albedo, normalized difference vegetation index (NDVI), hyperspectral characteristics (350-1800 nm), surface reflectance anisotropy, brightness temperature, fraction of absorbed photosynthetic active radiation (FAPAR), biomass, vegetation water content, and land-atmosphere exchanges of carbon (NEE) and energy. The Dahra field site experiences a typical Sahelian climate and is covered by coexisting trees (~3% canopy cover) and grass species, characterizing large parts of the Sahel. This makes the site suitable for investigating relationships between ecosystem properties and hydroclimatic variables for semiarid savanna ecosystems of the region. There were strong interannual, seasonal and diurnal dynamics in NEE, with high values of ~-7.5 g C m(-2)  day(-1) during the peak of the growing season. We found neither browning nor greening NDVI trends from 2002 to 2012. Interannual variation in species composition was strongly related to rainfall distribution. NDVI and FAPAR were strongly related to species composition, especially for years dominated by the species Zornia glochidiata. This influence was not observed in interannual variation in biomass and vegetation productivity, thus challenging dryland productivity models based on remote sensing. Surface reflectance anisotropy (350-1800 nm) at the peak of the growing season varied strongly depending on wavelength and viewing angle thereby having implications for the design of remotely sensed spectral vegetation indices covering different wavelength regions. The presented time series of in situ data have great potential for dryland dynamics studies, global climate change related research and evaluation and parameterization of remote sensing products and dynamic vegetation models.

Lu AA21004, a novel multimodal antidepressant, produces regionally selective increases of multiple neurotransmitters--a rat microdialysis and electrophysiology study.

The monoaminergic network, including serotonin (5-HT), norepinephrine (NE), and dopamine (DA) pathways, is highly interconnected and has a well-established role in mood disorders. Preclinical research suggests that 5-HT receptor subtypes, including 5-HT1A, 5-HT1B, 5-HT3, and 5-HT7 receptors as well as the 5-HT transporter (SERT), may have important roles in treating depression. This study evaluated the neuropharmacological profile of Lu AA21004, a novel multimodal antidepressant combining 5-HT3 and 5-HT7 receptor antagonism, 5-HT1B receptor partial agonism, 5-HT1A receptor agonism, and SERT inhibition in recombinant cell lines. Extracellular 5-HT, NE and DA levels were evaluated in the ventral hippocampus (vHC), medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) after acute and subchronic treatment with Lu AA21004 or escitalopram. The acute effects of LuAA21004 on NE and DA neuronal firing were also evaluated in the locus coeruleus (LC) and ventral tegmental area (VTA), respectively. Acute Lu AA21004 dose-dependently increased 5-HT in the vHC, mPFC and NAc. Maximal 5-HT levels in the vHC were higher than those in the mPFC. Furthermore, mPFC 5-HT levels were increased at low SERT occupancy levels. In the vHC and mPFC, but not the NAc, high Lu AA21004 doses increased NE and DA levels. Lu AA21004 slightly decreased LC NE neuronal firing and had no effect on VTA DA firing. Results are discussed in context of occupancy at 5-HT3, 5-HT1B and 5-HT1A receptors and SERT. In conclusion, Lu AA21004, acting via two pharmacological modalities, 5-HT receptor modulation and SERT inhibition, results in a brain region-dependent increase of multiple neurotransmitter concentrations.