Miracle-dz/UniFAR-FTUs huggingface dataset:
Interplay of PNPLA3 and HSD17B13 Variants in Modulating the Risk of Hepatocellular Carcinoma among Hepatitis C Patients

A single-nucleotide polymorphism causing a C to G change in the PNPLA3 gene (rs738409) is associated with disease severity and development of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease; the insertion variant rs72613567:TA of the 17β-hydroxysteroid dehydrogenase type 13 (HSD17B13) mitigates this detrimental effect. Our aim was to evaluate if the same holds true in chronic hepatitis C virus infection (HCV). With a case control retrospective study design, we selected 110 patients who developed HCC on a background of HCV infection, matching each patient for sex and age (±30 months) to three HCV-infected, non-HCC patients. All participants underwent genotyping for PNPLA3 and HSD17B13 gene variants. Both univariate and multivariate analyses of risk factors for advanced disease and HCC were performed. Carriage of PNPLA3 G∗ allele was associated with a trend of progressively more severe liver disease, from mild fibrosis to significant fibrosis, cirrhosis, and HCC (p = 0.007). When the HSD17B13:TA status of these patients was taken into account, the abovementioned trend was strengthened among HSD17B13 major allele homozygotes and completely blunted among carriers of the minor allele (p = 0.0003 and 0.953, respectively). In a conditional logistic regression model including diabetes and AST to platelet ratio index among predictor variables, the unfavourable genetic profile characterized by the coexistence of the PNPLA3 minor allele and HSD17B13 major allele (vs. all other possible combinations) was an independent risk factor for HCC (OR = 2.00, 95% CI: 1.23-3.26) together with a history of alcohol abuse. In conclusion, carriage of the combination PNPLA3 minor allele and HSD17B13 major allele may represent a risk factor for HCC among HCV-infected patients. The interplay between the two genes may explain some of the controversy on this topic and may be exploited to stratify HCC risk in hepatitis C.
The role of PNI to predict survival in advanced hepatocellular carcinoma treated with Sorafenib

Background and aims The present study aims to investigate the role of the prognostic nutritional index (PNI) on survival in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Methods This multicentric study included a training cohort of 194 HCC patients and three external validation cohorts of 129, 76 and 265 HCC patients treated with Sorafenib, respectively. The PNI was calculated as follows: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). Univariate and multivariate analyses were performed to investigate the association between the covariates and the overall survival (OS). Results A PNI cut-off value of 31.3 was established using the ROC analysis. In the training cohort, the median OS was 14.8 months (95% CI 12–76.3) and 6.8 months (95% CI 2.7–24.6) for patients with a high (>31.3) and low (<31.3) PNI, respectively. At both the univariate and the multivariate analysis, low PNI value (p = 0.0004), a 1-unit increase of aspartate aminotransferase (p = 0.0001), and age > 70 years (p< 0.0038) were independent prognostic factors for OS. By performing the same multivariate analysis of the training cohort, the PNI <31.3 versus >31.3 was found to be an independent prognostic factor for predicting OS in all the three validation cohorts. Conclusions PNI represents a prognostic tool in advanced HCC treated with first-line Sorafenib. It is readily available and low-cost, and it could be implemented in clinical practice in patients with HCC.
Ultrastructural modifications of rat liver cells induced by lead nitrate

Abstract Lead nitrate administration dramatically modified liver cells and sinusoids assayed by scanning and transmission electron microscopy. Hepatocytes became more roundish and many apoptot‐ic cells were visible both inside the parenchyma and in the sinusoidal lumen. Many of the those free in the sinusoids, probably derives from Kupffer cells, since their number was apparently reduced and some showed nuclear chromatin condensation. The remaining healthy Kupffer cells were often observed present beneath the endothelial wall into the space of Disse or between the disconnected hepatocytes. Except for scarce signs of apoptosis and a reduced number of fenestrae that were sometimes observed, the endothelial lining cells appeared almost healthy. At the longer times following treatment, further modifications of the liver were described: the presence of fribrotic materials, many sinusoids destroyed and enlarged spaces between hepatocytes.
Response to “Lupus anticoagulant is frequent in patients with Covid‐19” (JTH‐2020‐00483)

We appreciate the opportunity to respond to the letter from Dr. Inès Harzallah, et al. Antiphospholipid antibody assays including lupus anticoagulant (LAC), anticardiolipin and anti-β2-glycoprotein I have also been performed in dozens of our patients, however, very few of them got positive results, we don't think that antiphospholipid antibody exists universally in COVID-19 patients. In addition, two of the three reported cases with antiphospholipid antibodies mentioned in the letter [1] also seem to meet the International Society on Haemostasis and Thrombosis (ISTH) criteria of disseminated intravascular coagulation [2], the causality between antiphospholipid antibodies and thrombosis in these cases is still uncertain.
SARS-CoV-2 receptor ACE2 expression in the human heart: cause of a post-pandemic wave of heart failure?

The current ongoing pandemic COVID-19 (coronavirus disease outbreak at the end of 2019) is based on a positive-sense single-stranded RNA virus associated with a nucleoprotein within a capsid comprised of matrix proteins. Together with SARS-CoV and MERS-CoV, SARS-CoV-2 belongs to human betacoronaviruses. Although those viruses show many similarities, there are differences in their genomic and phenotypic structure resulting in huge consequences for their patho-genesis. Whereas fatality rates with previous SARS-CoV and MERS-CoV outbreaks were much higher, SARS-CoV-2 shows several unique features. There is a much higher contagiosity with a high prevalence for asymptomatic disease spreaders. The prolonged incu-bation period additionally helps the virus spreading towards a world-wide pandemic.
Bird diversity and environmental gradients in Britain: a test of the species–energy hypothesis

1. We tested the species diversity–energy hypothesis using the British bird fauna. This predicts that temperature patterns should match diversity patterns. We also tested the hypothesis that the mechanism operates directly through effects of temperature on thermoregulatory loads; this further predicts that seasonal changes in temperature cause matching changes in patterns of diversity, and that species’ body mass is influential. 2. We defined four assemblages using migration status (residents or visitors) and season (summer or winter distribution). Records of species’ presence/absence in a total of 2362, 10 × 10-km, quadrats covering most of Britain were used, together with a wide selection of habitat, topographic and seasonal climatic data. 3. We fitted a logistic regression model to each species’ distribution using the environmental data. We then combined these individual species models mathematically to form a diversity model. Analysis of this composite model revealed that summer temperature was the factor most strongly associated with diversity. 4. Although the species–energy hypothesis was supported, the direct mechanism, predicting an important role for body mass and matching seasonal patterns of change between diversity and temperature, was not supported. 5. However, summer temperature is the best overall explanation for bird diversity patterns in Britain. It is a better predictor of winter diversity than winter temperature. Winter diversity is predicted more precisely from environmental factors than summer diversity. 6. Climate change is likely to influence the diversity of different areas to different extents; for resident species, low diversity areas may respond more strongly as climate change progresses. For winter visitors, higher diversity areas may respond more strongly, while summer visitors are approximately neutral.
Fertilization in northern forests – biological, economic and environmental constraints and possibilities

Forests of northern ecosystems respond slowly to management activities and the possibilities to increase the growth in a short-term perspective and meet swift increases in society's demand for biomass are small. An exception among the silvicultural measures is fertilization which can be applied in combination with present management systems and, almost instantly, enhances forest productivity. There may, however, be both economic and environmental constraints to large-scale applications of fertilizers in forest. Here we review the literature concerning biomass production of forests under different fertilization regimens, environmental constraints and possibilities in northern forests on mineral soils. Further on we discuss the implications of both extensive and more intensive fertilization in relation to the developing bioeconomy, which encompasses the production and conversion of renewable biological resources into food, health and industrial products and energy. Fertilization in Sweden and Finland is currently practiced by extensive fertilization regimens where nitrogen fertilizers are applied once, or up to three times, during a rotation period, mainly in mature forest. This type of fertilization gives, in most cases, a small and transient effect on the environment as well as a high rate of return to the forest owner with low-economic risk. The increase in biomass production, however, is relatively small and consequently the impact on the processing industry and the bioeconomy is limited. More intensive fertilization regimens implying intensive fertilization starting in young forests may, on the other hand, considerably increase the biomass supply and value for the industry. The economic and environmental risks of this type of fertilization may, however, be larger and more research is needed on the effects on the stand level, and especially on the landscape level, including late rotation management of the forest.
Dopamine regulation of contextual fear and associated neural circuit function

Learning to associate certain contexts with threat and adapting to changing environmental contingencies by learning that such contexts are no longer associated with threat are both crucial for survival. Research over the last few decades has made considerable progress in determining the brain areas involved in the encoding, retrieval and extinction of contextual fear. These studies have identified the hippocampus and amygdala, along with the prefrontal cortex and other inter‐connected brain areas, as key players in contextual fear processing. In contrast to the neural circuit basis of contextual fear, the neurochemical mechanisms involved in its regulation remain poorly understood. Dopamine is well known for its role in appetitive learning but this neurotransmitter is also important for other types of learning, including spatial and aversive memory processing. Dopamine is ideally positioned to regulate contextual fear given that the areas involved receive dopamine input and express dopamine receptors. Moreover, neuronal activity, functional connectivity and synaptic plasticity in this neural circuitry are modulated by dopamine receptor signalling. Here, we review the evidence indicating that dopamine regulates various contextual fear processes, along with the more recent studies that have begun to elucidate the brain areas and neurophysiological mechanisms involved. From a fundamental research perspective, understanding how dopamine regulates contextual fear will lead to novel insights on the neurochemical modulation of neural circuit function underlying memory processing. This research may also have translational relevance given that contextual fear conditioning and extinction also provide useful preclinical models of certain aspects of anxiety‐related disorders and their treatment.
Ammonium uptake by seagrass epiphytes: Isolation of the effects of water velocity using an isotope label

In a series of flume experiments, 15N‐labeled ammonium was used to isolate the effects of water velocity on ammonium uptake by epiphytes from that of an assemblage of organisms that included seagrass leaves, epiphytes, and phytoplankton. Rates of NH4+ uptake for epiphytes, seagrass leaves, and the total assemblage were dependent on water velocity. Ammonium uptake rates for epiphytes, normalized to chlorophyll a, increased by an order of magnitude (0.65 to 6.8 × 1028 g N removed [mg Chl a]−1 s−1) over a range of velocity (0.02–0.20 m s−1) and were correlated to uptake by the entire assemblage. The relationship between NH4+ uptake and velocity for the epiphytes was within the range expected for mass transfer limited uptake, which suggests that water flow strongly influences NH4+ uptake by this important component of seagrass communities. Our results demonstrate that isotopically labeled nutrients can be used to isolate the effects of water velocity on rates of nutrient uptake by an individual component of a community and to evaluate how uptake rates for the component compare to those of the community as a whole.
Peptide Interference with APP and Tau Association: Relevance to Alzheimer’s Disease Amelioration

The two major proteins involved in Alzheimer’s disease (AD) are the amyloid precursor protein (APP) and Tau. Here, we demonstrate that these two proteins can bind to each other. Four possible peptides APP1 (390–412), APP2 (713–730), Tau1 (19–34) and Tau2 (331–348), were predicted to be involved in this interaction, with actual binding confirmed for APP1 and Tau1. In vivo studies were performed in an Alzheimer Disease animal model—APP double transgenic (Tg) 5xFAD—as well as in 5xFAD crossed with Tau transgenic 5xFADXTau (FT), which exhibit declined cognitive reduction at four months of age. Nasal administration of APP1 and Tau1 mixture, three times a week for four or five months, reduced amyloid plaque burden as well as the level of soluble Aβ 1–42 in the brain. The treatment prevented the deterioration of cognitive functions when initiated at the age of three months, before cognitive deficiency was evident, and also at the age of six months, when such deficiencies are already observed, leading to a full regain of cognitive function.
A genetically hmgb2 attenuated blood stage P. berghei induces crossed-long live protection

Due to the lack of efficiency to control malaria elicited by sub-unit vaccine preparations, vaccination with live-attenuated Plasmodium parasite as reported 70 years ago with irradiated sporozoites regained recently a significant interest. The complex life cycle of the parasite and the different stages of development between mammal host and anopheles do not help to propose an easy vaccine strategy. In order to achieve a complete long-lasting protection against Plasmodium infection and disease, we considered a genetically attenuated blood stage parasite in the hmgb2 gene coding for the high-mobility-group-box 2 (HMGB2). This Plasmodium protein belongs to the HMGB family and hold as the mammal proteins, a double life since it acts first as a nuclear factor involved in chromatin remodelling and transcription regulation and second, when secreted as an active pro-inflammatory alarmin protein. Even though the number of reports on whole living attenuated blood stage parasites is limited when compared to attenuated sporozoites, the results reported with Plasmodium KO parasites are very encouraging. In this report, we present a novel strategy based on pre-immunization with Δhmgb2PbNK65 parasitized red blood cells that confer long-lasting protection in a murine experimental cerebral malaria model against two highly pathogenic homologous and heterologous parasites.
Recent Progress on Lipid Intake and Chronic Kidney Disease

The incidence of chronic kidney disease (CKD) is associated with major abnormalities in circulating lipoproteins and renal lipid metabolism. This article elaborates on the mechanisms of CKD and lipid uptake abnormalities. The viewpoint we supported is that lipid abnormalities directly cause CKD, resulting in forming a vicious cycle. On the theoretical and experiment fronts, this inference has been verified by elaborately elucidating the role of lipid intake and accumulation as well as their influences on CKD. Taken together, these findings suggest that further understanding of lipid metabolism in CKD may lead to novel therapeutic approaches.
Alleviation of Fatty Liver by α-Linolenic Acid

We compared the efficacy of alpha-linolenic acid (α-LNA, n-3) and linoleic acid (LA, n-6) on orotic acid (OA)-induced fatty liver in Sprague-Dawley rats, Rats were fed semi-synthetic diets containing either LA or α-LNA With or without 1% OA for 2 wk, OA supplementation lowered serum lipids in LA+OA groups. In addition to the decline of serum lipids in α-LNA groups compared to LA groups, a further decrease was found in α-LNA+OA groups compared to LA+OA groups. OA-containing diets significantly increased the liver weights and triacylglycerol (TG) accumulations compared with the OA-free diets. These results were attributed to the significant increases in the activities of phosphatidate phosphohydrolase (PAP), a rate-limiting enzyme of TG synthesis, and glucose-6-phosphate dehydrogenase, a fatty acid synthesis-related enzyme. However, the increase of PAP activity was significantly less in the α-LNA+OA group as compared with the LA+OA group, These results suggest that dietary α-LNA alleviates OA-induced hepatic TG accumulation through the attenuation of hepatic TG synthesis in rats
Ewonetu Kebede and Feyisa Hundessa

The objective of this study was to determine effect of replacing grass hay with maize silage on milk production and composition. The study was conducted at Haramaya University dairy research farm -using sixteen crossbred dairy cows (Zebu × HolsteinFriesian) which were assigned to two treatment groups. Each treatment group consisted of eight cows and arranged in a completely randomized experimental design. Cows in both treatment groups were provided similar supplemental concentrate ration formulated from various ingredients but fed on different basal diets which were silage and grass hay. The feeding trial was conducted for a total of 90 days. Milk yield of individual cows were recorded every day and analyzed every two weeks for its chemical composition. Data were analyzed by t-Test for means. The group of cows fed on grass hay relatively produced higher milk yield (17.1) than cows fed on silage (16.1 liters per day). The protein, total solid, solid not fat, and milk urea nitrogen composition were found significantly different between a group of cows fed grass hay and silage. Silage-fed cows gave higher percentage of fat and protein content throughout the experimental period. Milk urea-nitrogen concentration was intensive in cows fed on hay and it was higher than the acceptable range (12 to 18 mg/dl) for the two experimental diets. In conclusion, farmers could use both grass hay and maize silage as substitute to each other in dairy cow diets that could ensure higher quantity and quality milk production.
Skin autofluorescence and malnutrition as predictors of mortality in persons receiving dialysis: a prospective cohort study.

BACKGROUND Skin autofluorescence (SAF), which is a measure of accumulation of advanced glycation end-products (AGE), and malnutrition are each associated with higher mortality in dialysis populations, although no studies have investigated these potentially related associations together. We simultaneously assessed SAF and malnutrition as risk factors for mortality in persons receiving dialysis. METHODS SAF was measured in 120 haemodialysis and 31 peritoneal dialysis patients using an AGE Reader (DiagnOptics, Groningen, The Netherlands). Dietary AGE, energy, protein and fat intake, handgrip strength, anthropometry, biochemistry and Subjective Global Assessment were also evaluated. Time to event was days from baseline to death, kidney transplantation or 30 September 2018. RESULTS Median observation time was 576 days, during which 33 (21.9%) patients died. Those who died had higher baseline SAF levels [3.8 ± 1.0 versus 3.3 ± 0.8 arbitrary units (AU); P = 0.001] and were more likely to be malnourished (58% versus 31%; P = 0.006). Malnourished persons who died had higher SAF values than those who died but were well-nourished (4.2 ± 1.1 versus 3.3 ± 0.7 AU; P = 0.007). Survival was significantly better in participants with baseline SAF below the median and in those well-nourished than those with baseline SAF above the median and in those malnourished, respectively. Multivariable analysis identified SAF [hazards ratio (HR) = 1.44; 95% confidence interval (CI) = 1.05-1.97; P = 0.02], malnutrition (HR = 2.35; 95% CI = 1.16-4.78; P = 0.02) and chronological age (HR = 1.60; 95% CI = 1.10-2.33; P = 0.01) as independent predictors of mortality. CONCLUSIONS Although higher SAF and malnutrition are potentially inter-related, they were both independently associated with increased mortality in this population. Interventions to improve outcomes by reducing SAF through correction of malnutrition or dietary AGE restriction require testing in prospective studies.
Treatment of Congenital Pseudarthrosis with Endomedullary Nail and Low Frequency Pulsing Electromagnetic Fields: A Controlled Study

We report our experience in the treatment of congenital pseudarthrosis with pulsing electromagnetic fields in a controlled study. Both the stimulated and control groups received the same surgical procedure: excision of the pseudarthrosis site, reduction and fixation by intramedullary nail. Stimulation with electromagnetic fields was begun within 3 days after surgery. The orthopaedic treatment was the same for all patients. The stimulation lasted up to 12 months. All patients were followed at least 24 months after the surgery. The data showed that the surgical approach in association with pulsing electromagnetic-field stimulation gave significantly better results than surgery alone.
Foraging Behaviour of Goats and Sheep in the Caatinga of Brazil

(1) This study quantified the seasonal feeding patterns of sheep and goats by determining the time spent per feeding station (TFS), and the proportion of foraging time spent by goats and sheep in the bipedal stance and feeding at several heights in the quadrupedal stance. The results were compared to determine whether goats gain a nutritional advantage over sheep by feeding bipedally. The animals grazed caatinga vegetation, a mix of deciduous trees with an annual herbaceous understorey that is strongly influenced by wet and dry seasons. (2) Sheep TFS was c. 8 s during the wet and dry seasons. The TFS by goats was 8 s in the dry season, but > 20 s in the wet season. (3) Goats and sheep grazed in different layers of vegetation. Sheep spent 36% of their foraging time grazing at or near ground level, compared with 18% for goats (P< 005). Goats stood on their hind legs for 4% of their foraging time overall; for 1 % of their foraging time in the dry season; and for 8% in the wet season. There was no nutritional advantage to goats in using a bipedal stance, compared with quadrupedally grazing sheep, because in the season of nutritional stress (the dry season) there was little or no forage in the bipedal foraging zone.
The March of Monocytes in Atherosclerosis: One Cell at a Time.

The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. Correspondence to: Rajat M. Gupta, MD, Department of Medicine, Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School, 77 Ave Louis Pasteur, Boston, MA 02115. Email rgupta@bwh.harvard. edu For Sources of Funding and Disclosures, see page 1326. © 2020 American Heart Association, Inc. EDITORIAL