Miracle-dz/UniFAR-FTUs huggingface dataset:
Real-world treatment practice in patients with advanced melanoma

Introduction The treatment outcomes of patients with advanced/metastatic melanoma were poor before the use of new therapeutic options. Material and methods A retrospective analysis was conducted among 287 patients with unresectable stage III and stage IV melanoma treated at the Maria Sklodowska-Curie National Research Institute of Oncology Cracow Branch, from 2013 to 2019. All enrolled patients were treated with immunotherapy (IT; consisting of pembrolizumab/nivolumab, or ipilimumab) or target therapy (TT; consisting of vemurafenib ±cobimetinib or dabrafenib ±trametinib) in at least one treatment line. Results mutation was detected in 152 (55%) patients. In general, the majority of patients (92%) were in very good or good condition (Eastern Cooperative Oncology Group [ECOG] 0 or 1). Brain metastasis was detected in 64 (22%) patients. Median OS and PFS in the experimental group from the beginning of the first-line treatment were 14.9 and 6.7 months, respectively. Across the study population, as a first-line treatment patients received IT, TT as well as CHT, and the median OS was 19.2, 12.6 and 15.9 months, respectively. Multivariate analysis confirmed that normal LDH levels, no brain metastases, ECOG 0, and objective response to the treatment were strong predictors of longer OS. For PFS, absence of brain metastases, ECOG 0, and treatment response were found to be predictive factors on multivariate analysis. Conclusions The administration of new therapies for the treatment of patients with advanced/disseminated melanoma significantly prolonged survival in this group of patients. Nevertheless, further studies should be conducted to assess the effectiveness of various sequences of treatment.
Effects on Gastroesophageal Reflux of Donkey Milk-Derived Human Milk Fortifier Versus Standard Fortifier in Preterm Newborns: Additional Data from the FortiLat Study

Background: Feeding intolerance is a frequent diagnosis in very preterm infants. As seen in the FortiLat trial, human milk fortification with the new donkey milk-derived human milk fortifier (DF) seems to improve feeding tolerance in these infants. The aim of this study was to evaluate the effects of using the DF compared with bovine milk-derived fortifier (BF) on gastroesophageal reflux (GER) in very low birth weight (VLBW) infants. Methods: Over a total of 156 preterm infants were enrolled into the FortiLat trial (GA <32 weeks and birth weight <1500 g) and randomized into the BF arm or DF arm, and we selected all infants with clinical signs of GER and cardiorespiratory (CR) symptoms. All the infants underwent CR and multichannel intraluminal impedance and pH (MII/pH) monitoring associated with gastric ultrasound to evaluate GER and gastric emptying time. Results: 10 infants were enrolled, and 5 were in the DF arm. At MII/pH, infants enrolled into the DF arm showed a lower GER frequency than BF arm infants (p = 0.036). Half gastric emptying time was similar in DF and BF arm infants (p = 0.744). Conclusion: The use of donkey-derived human milk fortifier reduced the GER frequency and consequently should be recommended in infants with feeding intolerance.
Testing for top‐down cascading effects in a biomass‐driven ecological network of soil invertebrates

Abstract To investigate the structural changes of a food‐web architecture, we considered real data coming from a soil food web in one abandoned pasture with former low‐pressure agriculture management and we reproduced the corresponding ecological network within a multi‐agent fully programmable modeling environment in order to simulate dynamically the cascading effects due to the removal of entire functional guilds. We performed several simulations differing from each other for the functional implications. At the first trophic level, we simulated a removal of the prey, that is, herbivores and microbivores, while at the second trophic level, we simulated a removal of the predators, that is, omnivores and carnivores. The five main guilds were removed either separately or in combination. The alteration in the food‐web architecture induced by the removal of entire functional guilds was the highest when the entire second trophic level was removed, while the removal of all microbivores caused an alteration in the food‐web structure of less than 5% of the total changes due to the removal of opportunistic and predatory species. Omnivores alone account for the highest shifts in time of the numerical abundances of the remaining species, providing computational evidence of the importance of the degree of omnivory in the stabilization of soil biota.
The Powdered Root of Eurycoma longifolia Jack Improves Beta-Cell Number and Pancreatic Islet Performance through PDX1 Induction and Shows Antihyperglycemic Activity in db/db Mice

Non-insulin-dependent diabetes mellitus (NIDDM) is a common metabolic disorder worldwide. In addition to the chief feature of long-standing hyperglycemia, dyslipidemia, hyperinsulinemia, and a number of complications develop in parallel. It is believed that an adequate control of blood glucose levels can cause these complications to go into remission. This study was performed to evaluate the antidiabetic activity of Eurycoma longifolia Jack (EL) in vivo. The blood-glucose-lowering activity of EL was studied in db/db mice administered crude powdered EL root (25, 50, and 100 mg/kg) orally for eight weeks. At the end of the study, HbA1c, insulin, plasma lipid levels, and histopathology were performed. Powdered EL root showed significant antihyperglycemic activity along with the control of body weight. After eight weeks of treatment, both the blood cholesterol level and the glycogen deposit in hepatocytes were remarkably lower, whereas the secreting insulin level was elevated. An improvement in islet performance was manifested as an increase in beta-cell number and pancreatic and duodenal homeobox 1 (PDX1) expression. Neogenesis or formation of new islets from pancreatic duct epithelial cells seen in the EL-treated group was encouraging. This study confirms the antihyperglycemic activity of EL through PDX1-associated beta-cell expansion resulting in an enhancement of islet performance.
Evolution of the Teaching of Animal Welfare Science, Ethics and Law in European Veterinary Schools (2012–2019)

Simple Summary Nowadays, animal welfare is seen as a ‘common good’ and a societal expectation. Veterinarians are expected to promote and ensure the welfare of animals under their care by using their scientific knowledge and skills in ethical reasoning and advocacy. In 2013, the Federation of Veterinarians of Europe (FVE) and the European Association of Establishments for Veterinary Education (EAEVE) adopted the Day-1 competences on animal welfare science, ethics and law for veterinary undergraduate education after having surveyed 33 European veterinary schools in 2012. In 2019, a follow-up survey was done to monitor the evolution of animal welfare teaching in Europe. A total of 82 responses were received, representing 57 veterinary schools from 25 European countries. Overall results showed that the teaching of animal welfare science, ethics and law has increased in response to growing societal needs, and that welfare is more and more internally embedded in the profession, which is reflected in the curriculum. Abstract Nowadays, animal welfare is seen as a ‘common good’ and a societal expectation. Veterinarians are expected to promote and ensure the welfare of animals under their care by using their scientific knowledge and skills in ethical reasoning and advocacy. Veterinary education must equip veterinary graduates with the necessary competences to fulfil these roles. In 2013, the Federation of Veterinarians of Europe (FVE) and the European Association of Establishment of Veterinary Education (EAEVE) adopted the Day-1 competences on animal welfare science, ethics and law for veterinary undergraduate education after having surveyed European veterinary schools in 2012. In 2019, the FVE carried out a follow-up survey to monitor the evolution of animal welfare teaching in Europe. A total of 82 responses were received, representing 57 faculties from 25 European countries. Overall results showed that the teaching of animal welfare science, ethics and law has increased in response to growing societal needs, and that welfare is more and more internally embedded in the profession, which is reflected in the curriculum. Nevertheless, at least one quarter of European schools still only partially meet the 2013 Day-1 competencies. This indicates the need for greater efforts, both from the EAEVE and from individual schools, to ensure that the teaching of animal welfare across Europe is standardised.
Economic Viability of Adoption of Automated Oestrus Detection Technologies on Dairy Farms: A Review

Simple Summary The accurate and timely detection of oestrus is a central element of good dairy herd management as it ultimately determines the level of milk production and is core to the economic viability of the farm business. However, the traditional method of oestrus detection, which occurs by observing the dairy cows standing immobile while being mounted, is usually time-consuming, repetitive and requires considerable skill and experience on the part of the farmer to attain a reasonable level of efficiency. Given the limitation of the traditional method of oestrus detection, a number of automated oestrus detection (AOD) technologies have been developed. However, the rate of adoption of these technologies remains low. One reason that has been proposed for farmers’ low adoption of such technologies has been their lack of knowledge around the potential economic returns from investing in AOD technologies. In this paper, we review the empirical literature on the viability of investment in AOD technologies from an economic perspective. The conclusion of this study provides evidence from which farmers can make more informed decisions in relation to investing in AOD technologies. The review and analysis is also of importance for informing policy, as it provides an examination of the incentives and levers that could improve productivity on dairy farms. Abstract The decision for dairy farmers to invest in automated oestrus detection (AOD) technologies involves the weighing up of the costs and benefits of implementation. In this paper, through a review of the existing literature, we examine the impacts of investment in AOD technologies in relation to the profitability and technical performance of dairy farms. Peer-reviewed articles published between 1970 and 2019 on the investment viability of AOD technologies were collated and analysed. We capture the different measures used in assessing the economic performance of investment in AOD technologies over time which include net present value (NPV), milk production, Benefit-Cost Ratio (BCR), internal rate of return (IRR) and payback period (PBP). The study concludes that investment in AOD technologies is not only worthwhile but also contributes to farm profitability.
Affective and Psychotic Disorders in War-Torn Eastern Part of the Democratic Republic of the Congo: A Cross-Sectional Study

Background There is lack of information about prevalence of affective and psychotic disorders triggered by traumatic events among people living in war-affected regions. This study is aimed at determining the prevalence rate of affective and psychotic disorders and the associated factors in a war-torn eastern part of Democratic Republic of the Congo. Methods This epidemiological cross-sectional descriptive study was carried out from 1st January 2019 to 31st December 2019 at Cepima and Muyisa health centers. This study enrolled 344 patients that had experienced traumatic events in Eastern Democratic Republic of the Congo from the 1119 participants, of whom 229 had positive bipolar affective disorder and 115 patients had psychotic disorders. Results The results revealed that bipolar affective disorders were two times more than psychotic disorders. Sexual abuse, sudden death of a relative, kidnapping, the physical torture, and childhood trauma were the psychological factors correlated to the occurrence of bipolar affective and psychotic disorders. Conclusions It was concluded that the traumatic experiences were precursors for the occurrence of bipolar affective and psychotic spectrum disorders.
Silver Nanoparticle Production by Ruta graveolens and Testing Its Safety, Bioactivity, Immune Modulation, Anticancer, and Insecticidal Potentials

Ruta graveolens, a plant belonging to the family Rutaceae, is traditionally used as a medicinal plant and a flavoring agent in food. This work aimed to prepare silver nanoparticles (AgNPs) using the ethanol extract from R. graveolens leaves and test different biological activities as well as insecticidal potentials in the extract and extract prepared AgNPs. Dried and powdered R. graveolens leaves were subjected to extraction using ethanol, and this extract was used to synthesize AgNPs. AgNP synthesis was monitored by the change in color, UV spectrophotometry, and electron microscopy (scanning). Fourier transform infrared (FT-IR) spectroscopy was used to monitor the functional groups in the extracts. Immunological, physiological, anticancer, antibacterial, and insecticidal potentials of the extract and its prepared AgNPs were tested. Results showed the ability of the leaf extract to synthesize. SEM examination revealed a spherical shape of AgNPs with a size of 40–45 nm. The extract contained many functional groups as indicated by FT-IR. The extract alone inhibited the growth of normal rat splenic cells, while the extract containing AgNPs stimulated its growth. Extract alone stimulated HeLa cell proliferation and inhibited HepG2 growth, while both cell line growth was inhibited by the extract containing AgNPs. Both the extract and extract with AgNPs were safe on RBCs and did not cause any severe elevation in liver enzymes. The extract alone and with AgNPs showed insecticidal activity against Culex pipiens. Our findings suggest that the R. graveolens leaf extract, alone or with AgNPs, is biologically safe on animal cells and has antibacterial, insecticidal, and immunomodulation potentials.
Genetic diversity at major histocompatibility complex and its effect on production and immune traits in indigenous chicken breeds of India

Abstract The genetic diversity at major histocompatibility complex (MHC) in indigenous chicken breeds of India (Ghagus and Nicobari) in comparison with the White Leghorn (WLH) breed was investigated by genotyping the MHC-linked LEI0258 marker. Altogether 38 alleles and 96 genotypes were observed among three breeds. The observed and effective alleles were highest in Ghagus (23, 8.3) followed by Nicobari (14, 3.2) and WLH (10 and 2.2) breeds. The size of alleles ranged from 193 to 489 bp in Ghagus, 193 to 552 bp in Nicobari and 241 to 565 bp in the WLH breed. The number of private alleles was also highest in Ghagus (18) followed by Nicobari (8) and WLH (5) breeds. The most frequent allele was 261 bp in WLH (66 %), 343 bp in Nicobari (50.4 %) and 309 bp in the Ghagus (28.15 %) breed. Observed and expected heterozygosities were highest in Ghagus (0.83, 0.88) followed by Nicobari (0.58, 0.68) and WLH (0.53, 0.54). The genetic distance (Nei) between Ghagus and Nicobari breeds (2.24) was higher as compared to that of Ghagus and WLH (1.23) and that between Nicobari and WLH breeds (0.89). Association analysis revealed significant influence of MHC alleles on body weight, egg production in Ghagus and WLH breeds and antibody titres to Newcastle disease vaccine in the Nicobari breed.
Assessing biotic and abiotic effects on forest productivity in three temperate forests

Abstract It is well understood that biotic and abiotic variables influence forest productivity. However, in regard to temperate forests, the relative contributions of the aforementioned drivers to biomass demographic processes (i.e., the growth rates of the survivors and recruits) have not received a great deal of attention. Thus, this study focused on the identification of the relative influencing effects of biotic and abiotic variables in the demographic biomass processes of temperate forests. This study was conducted in the Changbai Mountain Nature Reserve, in northeastern China. Based on the observational data collected from three 5.2‐hectare forest plots, the annual above‐ground biomass (AGB) increment (productivity) of the surviving trees, recruits, and the total tree community (survivors + recruits) were estimated. Then, the changes in the forest productivity in response to biotic variables (including species diversity, structural diversity, and density variables) along with abiotic variables (including topographic and soil variables) were evaluated using linear mixed‐effect models. This study determined that the biotic variables regulated the variabilities in productivity. Density variables were the most critical drivers of the annual AGB increments of the surviving trees and total tree community. Structural diversity enhanced the annual AGB increments of the recruits, but diminished the annual AGB increments of the surviving trees and the total tree community. Species diversity and abiotic variables did not have impacts on the productivity in the examined forest plots. The results highlighted the important roles of forest density and structural diversity in the biomass demographic processes of temperate forests. The surviving and recruit trees were found to respond differently to the biotic variables, which suggested that the asymmetric competition had shaped the productivity dynamics in forests. Therefore, the findings emphasized the need to consider the demographic processes of forest productivity to better understand the functions of forests.
Autophagy Upregulation by the TFEB Inducer Trehalose Protects against Oxidative Damage and Cell Death Associated with NRF2 Inhibition in Human RPE Cells

Trehalose is a natural dietary molecule that has shown antiaging and neuroprotective effects in several animal models of neurodegenerative diseases. The role of trehalose in the management of age-related macular degeneration (AMD) is yet to be investigated and whether trehalose could be a remedy for the treatment of diseases linked to oxidative stress and NRF2 dysregulation. Here, we showed that incubation of human retinal pigment epithelial (RPE) cells with trehalose enhanced the mRNA and protein expressions of TFEB, autophagy genes ATG5 and ATG7, as well as protein expressions of macroautophagy markers, LC3B and p62/SQTM1, and the chaperone-mediated autophagy (CMA) receptor LAMP2. Cathepsin D, a hydrolytic lysosomal enzyme, was also increased by trehalose, indicating higher proteolytic activity. Moreover, trehalose upregulated autophagy flux evident by an increase in the endogenous LC3B level, and accumulation of GFP-LC3B puncta and free GFP fragments in GFP-LC3 – expressing cells in the presence of chloroquine. In addition, the mRNA levels of key molecular targets implicated in RPE damage and AMD, such as vascular endothelial growth factor- (VEGF-) A and heat shock protein 27 (HSP27), were downregulated, whereas NRF2 was upregulated by trehalose. Subsequently, we mimicked in vitro AMD conditions using hydroquinone (HQ) as the oxidative insult on RPE cells and evaluated the cytoprotective effect of trehalose compared to vehicle treatment. HQ depleted NRF2, increased oxidative stress, and reduced the viability of cells, while trehalose pretreatment protected against HQ-induced toxicity. The cytoprotection by trehalose was dependent on autophagy but not NRF2 activation, since autophagy inhibition by shRNA knockdown of ATG5 led to a loss of the protective effect. The results support the transcriptional upregulation of TFEB and autophagy by trehalose and its protection against HQ-induced oxidative damage in RPE cells. Further investigation is, therefore, warranted into the therapeutic value of trehalose in alleviating AMD and retinal diseases associated with impaired NRF2 antioxidant defense.
Serum and Muscle 1H NMR-Based Metabolomics Profiles Reveal Metabolic Changes Influenced by a Maternal Leucine-Rich Diet in Tumor-Bearing Adult Offspring Rats

A maternal leucine-rich diet showed a positive effect on the gastrocnemius muscle of adult tumor-bearing offspring. To improve the understanding of the metabolic alterations of cancer cachexia and correlate this to preventive treatment, we evaluated the 1H NMR metabolic profiles from serum and gastrocnemius muscle samples of adult Wistar rats. These profiles were initially analyzed, and chemometrics tools were applied to investigate the following groups: C, control group; W, tumor-bearing group; L, the group without tumors and with a maternal leucine-rich diet; WL, the tumor-bearing group with a maternal leucine-rich diet. Tumor growth that led to a high protein breakdown in the W group was correlated to serum metabolites such as tyrosine, phenylalanine, histidine, glutamine, and tryptophan amino acids and uracil. Also, decreased muscle lactate, inversely to serum content, was found in the W group. Conversely, in the WL group, increased lactate in muscle and serum profiles was found, which could be correlated to the maternal diet effect. The muscle lipidomics and NAD+, NADP+, lysine, 4-aminohippurate, and glutamine metabolites pointed to modified energy metabolism and lower muscle mass loss in the WL group. In conclusion, this exploratory metabolomics analyses provided novel insights related to the Walker-256 tumor-bearing offspring metabolism modified by a maternal leucine-rich diet and the next steps in its investigation.
Effect of eight weeks high intensity aerobic exercise on C-reactive protein levels in obese middle-aged men

Introduction: C-reactive protein (CRP) is a marker of chronic systemic inflammation frequently used in cardiovascular disease risk assessment. The aim of this study was to investigate CRP concentrations in middle-aged men after 8 weeks high intensity aerobic exercise. Material & Methods: Twenty two sedentary obese middleaged men (aged: 46.4 ± 2.3 years and body mass index (BMI): 32.8 ± 2.0 kg/m; ± SD) volunteered to participate in this study. The subjects were randomly assigned to training group (n=11) or control group (n=11). The training group performed high intensity aerobic training 3 days a week for 8 weeks at an intensity corresponding to 75-80% individual maximum oxygen consumption for 45 min. Results: The results showed that the body weight, BMI, body fat percent and WHR were decreased and VO2max was increased in the training group compared to the control group (P<0.05). After 8 weeks, the training group resulted in 16 F. Hosseini, N. Abdollahpur, E. Bahrami Abdehgah a significant decrease (58.7 %) in the CRP in compared with the control group. Conclusions: The results suggest high intensity aerobic exercise improves body composition and decreases CRP concentrations in obese middle-aged men.