Miracle-dz/UniFAR-FTUs huggingface dataset:
A Basic Model to Predict Enteric Methane Emission from Dairy Cows and Its Application to Update Operational Models for the National Inventory in Norway

Simple Summary Many techniques exist to quantify enteric methane (CH4) emissions from dairy cows. Since measurement on the entire national cow populations is not possible, it is necessary to use estimates for national inventory reporting. This study aimed to develop (1) a basic equation of enteric CH4 emissions from individual animals based on feed intake and nutrient contents of the diet, and (2) to update the operational way of calculation used in the Norwegian National Inventory Report based on milk yield and concentrate share of the diet. An international database containing recently published data was used for this updating process. By this the accuracy of the CH4 production estimates included in the national inventory was improved. Abstract The aim of this study was to develop a basic model to predict enteric methane emission from dairy cows and to update operational calculations for the national inventory in Norway. Development of basic models utilized information that is available only from feeding experiments. Basic models were developed using a database with 63 treatment means from 19 studies and were evaluated against an external database (n = 36, from 10 studies) along with other extant models. In total, the basic model database included 99 treatment means from 29 studies with records for enteric CH4 production (MJ/day), dry matter intake (DMI) and dietary nutrient composition. When evaluated by low root mean square prediction errors and high concordance correlation coefficients, the developed basic models that included DMI, dietary concentrations of fatty acids and neutral detergent fiber performed slightly better in predicting CH4 emissions than extant models. In order to propose country-specific values for the CH4 conversion factor Ym (% of gross energy intake partitioned into CH4) and thus to be able to carry out the national inventory for Norway, the existing operational model was updated for the prediction of Ym over a wide range of feeding situations. A simulated operational database containing CH4 production (predicted by the basic model), feed intake and composition, Ym and gross energy intake (GEI), in addition to the predictor variables energy corrected milk yield and dietary concentrate share were used to develop an operational model. Input values of Ym were updated based on the results from the basic models. The predicted Ym ranged from 6.22 to 6.72%. In conclusion, the prediction accuracy of CH4 production from dairy cows was improved with the help of newly published data, which enabled an update of the operational model for calculating the national inventory of CH4 in Norway.
RNAi-Mediated Screening of Selected Target Genes Against Culex quinquefasciatus (Diptera: Culicidae)

Abstract Culex quinquefasciatus, a member of the Culex pipiens complex, is widespread in Saudi Arabia and other parts of the world. It is a vector for lymphatic filariasis, Rift Valley fever, and West Nile virus. Studies have shown the deleterious effect of RNA interference (RNAi)-mediated knockdown of various lethal genes in model and agricultural pest insects. RNAi was proposed as a tool for mosquito control with a focus on Aedes aegypti and Anopheles gambiae. In this study, we examined the effect of RNAi of selected target genes on both larval mortality and adult emergence of Cx. quinquefasciatus through two delivery methods: soaking and nanoparticles. Ten candidate genes were selected for RNAi based on their known lethal effect in other insects. Disruption of three genes, chitin synthase-1, inhibitor of apoptosis 1, and vacuolar adenosine triphosphatase, resulted in the highest mortality among the selected genes using the two treatment methods. Silencing the other seven genes resulted in a medium to low mortality in both assays. These three genes are also active against a wide range of insects and could be used for RNAi-based mosquito control in the future.
Chronic Kidney Disease-Associated Itch (CKD-aI) in Children—A Narrative Review

Chronic kidney disease (CKD) is a condition of widespread epidemiology and serious consequences affecting all organs of the organism and associated with significant mortality. The knowledge on CKD is rapidly evolving, especially concerning adults. Recently, more data is also appearing regarding CKD in children. Chronic itch (CI) is a common symptom appearing due to various underlying dermatological and systemic conditions. CI may also appear in association with CKD and is termed chronic kidney disease-associated itch (CKD-aI). CKD-aI is relatively well-described in the literature concerning adults, yet it also affects children. Unfortunately, the data on paediatric CKD-aI is particularly scarce. This narrative review aims to describe various aspects of CKD-aI with an emphasis on children, based on the available data in this population and the data extrapolated from adults. Its pathogenesis is described in details, focusing on the growing role of uraemic toxins (UTs), as well as immune dysfunction, altered opioid transmission, infectious agents, xerosis, neuropathy and dialysis-associated aspects. Moreover, epidemiological and clinical aspects are reviewed based on the few data on CKD-aI in children, whereas treatment recommendations are proposed as well, based on the literature on CKD-aI in adults and own experience in managing CI in children.
Diagnostic Power of Circulatory Metabolic Biomarkers as Metabolic Syndrome Risk Predictors in Community-Dwelling Older Adults in Northwest of England (A Feasibility Study)

Background: Metabolic Syndrome (MetS) is a cluster of risk factors for diabetes and cardiovascular diseases with pathophysiology strongly linked to aging. A range of circulatory metabolic biomarkers such as inflammatory adipokines have been associated with MetS; however, the diagnostic power of these markers as MetS risk correlates in elderly has yet to be elucidated. This cross-sectional study investigated the diagnostic power of circulatory metabolic biomarkers as MetS risk correlates in older adults. Methods: Hundred community dwelling older adults (mean age: 68.7 years) were recruited in a study, where their blood pressure, body composition and Pulse Wave Velocity (PWV) were measured; and their fasting capillary and venous blood were collected. The components of the MetS; and the serum concentrations of Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), Plasminogen Activator Inhibitor-I (PAI-I), Leptin, Adiponectin, Resistin, Cystatin-C, C-Reactive Protein (CRP), insulin and ferritin were measured within the laboratory, and the HOMA1-IR and Atherogenic Index of Plasma (AIP) were calculated. Results: Apart from other markers which were related with some cardiometabolic (CM) risk, after Bonferroni correction insulin had significant association with all components of Mets and AIP. These associations also remained significant in multivariate regression. The multivariate odds ratio (OR with 95% confidence interval (CI)) showed a statistically significant association between IL-6 (OR: 1.32 (1.06–1.64)), TNF-α (OR: 1.37 (1.02–1.84)), Resistin (OR: 1.27 (1.04–1.54)) and CRP (OR: 1.29 (1.09–1.54)) with MetS risk; however, these associations were not found when the model was adjusted for age, dietary intake and adiposity. In unadjusted models, insulin was consistently statistically associated with at least two CM risk factors (OR: 1.33 (1.16–1.53)) and MetS risk (OR: 1.24 (1.12–1.37)) and in adjusted models it was found to be associated with at least two CM risk factors and MetS risk (OR: 1.87 (1.24–2.83) and OR: 1.25 (1.09–1.43)) respectively. Area under curve (AUC) for receiver operating characteristics (ROC) demonstrated a good discriminatory diagnostics power of insulin with AUC: 0.775 (0.683–0.866) and 0.785 by cross validation and bootstrapping samples for at least two CM risk factors and AUC: 0.773 (0.653–0.893) and 0.783 by cross validation and bootstrapping samples for MetS risk. This was superior to all other AUC reported from the ROC analysis of other biomarkers. Area under precision-recall curve for insulin was also superior to all other markers (0.839 and 0.586 for at least two CM risk factors and MetS, respectively). Conclusion: Fasting serum insulin concentration was statistically linked with MetS and its risk, and this link is stronger than all other biomarkers. Our ROC analysis confirmed the discriminatory diagnostic power of insulin as CM and MetS risk correlate in older adults.
Interaction between a Novel Oligopeptide Fragment of the Human Neurotrophin Receptor TrkB Ectodomain D5 and the C-Terminal Fragment of Tetanus Neurotoxin

This article presents experimental evidence and computed molecular models of a potential interaction between receptor domain D5 of TrkB with the carboxyl-terminal domain of tetanus neurotoxin (Hc-TeNT). Computational simulations of a novel small cyclic oligopeptide are designed, synthesized, and tested for possible tetanus neurotoxin-D5 interaction. A hot spot of this protein-protein interaction is identified in analogy to the hitherto known crystal structures of the complex between neurotrophin and D5. Hc-TeNT activates the neurotrophin receptors, as well as its downstream signaling pathways, inducing neuroprotection in different stress cellular models. Based on these premises, we propose the Trk receptor family as potential proteic affinity receptors for TeNT. In vitro, Hc-TeNT binds to a synthetic TrkB-derived peptide and acts similar to an agonist ligand for TrkB, resulting in phosphorylation of the receptor. These properties are weakened by the mutagenesis of three residues of the predicted interaction region in Hc-TeNT. It also competes with Brain-derived neurotrophic factor, a native binder to human TrkB, for the binding to neural membranes, and for uptake in TrkB-positive vesicles. In addition, both molecules are located together in vivo at neuromuscular junctions and in motor neurons.
Assessment of Antidiabetic Activity of the Shikonin by Allosteric Inhibition of Protein-Tyrosine Phosphatase 1B (PTP1B) Using State of Art: An In Silico and In Vitro Tactics

Diabetes mellitus is a multifactorial disease that affects both developing and developed countries and is a major public health concern. Many synthetic drugs are available in the market, which counteracts the associated pathologies. However, due to the propensity of side effects, there is an unmet need for the investigation of safe and effective drugs. This research aims to find a novel phytoconstituent having diminished action on blood glucose levels with the least side effects. Shikonin is a naturally occurring naphthoquinone dying pigment obtained by the roots of the Boraginaceae family. Besides its use as pigments, it can be used as an antimicrobial, anti-inflammatory, and anti-tumor agent. This research aimed to hypothesize the physicochemical and phytochemical properties of Shikonin’s in silico interaction with protein tyrosine phosphate 1B, as well as it’s in vitro studies, in order to determine its potential anti-diabetic impact. To do so, molecular docking experiments with target proteins were conducted to assess their anti-diabetic ability. Analyzing associations with corresponding amino acids revealed the significant molecular interactions between Shikonin and diabetes-related target proteins. In silico pharmacokinetics and toxicity profile of Shikonin using ADMET Descriptor, Toxicity Prediction, and Calculate Molecular Properties tools from Biovia Discovery Studio v4.5. Filter by Lipinski and Veber Rule’s module from Biovia Discovery Studio v4.5 was applied to assess the drug-likeness of Shikonin. The in vitro studies exposed that Shikonin shows an inhibitory potential against the PTP1B with an IC50 value of 15.51 µM. The kinetics studies revealed that it has a competitive inhibitory effect (Ki = 7.5 M) on the enzyme system, which could be useful in the production of preventive and therapeutic agents. The findings of this research suggested that the Shikonin could be used as an anti-diabetic agent and can be used as a novel source for drug delivery.
Trends in Total, Added, and Natural Phosphorus Intake in Adult Americans, NHANES 1988–1994 to NHANES 2015–2016

Dietary phosphorus intake in the USA has been consistently greater than the Recommended Daily Allowance (RDA) with several studies reporting associations between intake and health risks as well as all-cause mortality within healthy subjects and patients with chronic kidney disease (CKD). The current study utilized a novel approach to calculate added phosphorus content in foods to determine sources (National Health and Nutrition Examination Survey, NHANES 2001–2016, n = 39,796) and trends in consumption (NHANES 1988–1994, 2001–2016, n = 55,744) of total, naturally occurring, and added phosphorus. Among adults (19+ years), the mean intake of total and natural phosphorus (mg/day) in 1988–1994 as compared with 2015–2016 increased (total: 1292 ± SE 11 vs. 1398 ± SE 17; natural: 1113 ± SE 10 vs. 1243 ± SE 16 mg/day); in contrast, added phosphorus intake decreased during this time (178 ± SE 2.9 vs. 155 ± SE 4.1 mg/day). Added phosphorus as a percent of total ranged from about 14.6% in 1988–1994 to about 11.6% in 2015–2016. The top five sources of total and naturally occurring phosphorus, representing approximately 20% of intake, were cheese, pizza, chicken (whole pieces), reduced-fat milk, and eggs/omelets. The top five sources of added phosphorus were cheese, soft drinks, cakes/pies, rolls/buns, and cookies/brownies, representing 45% of added phosphorus in the diet. Consumption of added phosphorus has decreased over the past few decades, possibly due to increased demand for foods with less additives/ingredients but may also be due to inaccurate phosphorus values in nutrition databases. Further studies are needed to validate the added phosphorus calculations utilized in this study and nutrition databases should consider providing added phosphorus content.
Sasso Pisano Geothermal Field Environment Harbours Diverse Ktedonobacteria Representatives and Illustrates Habitat-Specific Adaptations

The hydrothermal steam environment of Sasso Pisano (Italy) was selected to investigate the associated microbial community and its metabolic potential. In this context, 16S and 18S rRNA gene partial sequences of thermophilic prokaryotes and eukaryotes inhabiting hot springs and fumaroles as well as mesophilic microbes colonising soil and water were analysed by high-throughput amplicon sequencing. The eukaryotic and prokaryotic communities from hot environments clearly differ from reference microbial communities of colder soil sites, though Ktedonobacteria showed high abundances in various hot spring samples and a few soil samples. This indicates that the hydrothermal steam environments of Sasso Pisano represent not only a vast reservoir of thermophilic but also mesophilic members of this Chloroflexi class. Metabolic functional profiling revealed that the hot spring microbiome exhibits a higher capability to utilise methane and aromatic compounds and is more diverse in its sulphur and nitrogen metabolism than the mesophilic soil microbial consortium. In addition, heavy metal resistance-conferring genes were significantly more abundant in the hot spring microbiome. The eukaryotic diversity at a fumarole indicated high abundances of primary producers (unicellular red algae: Cyanidiales), consumers (Arthropoda: Collembola sp.), and endoparasite Apicomplexa (Gregarina sp.), which helps to hypothesise a simplified food web at this hot and extremely nutrient-deprived acidic environment.
Nanocomposite Materials Based on TMDCs WS2 Modified Poly(l-Lactic Acid)/Poly(Vinylidene Fluoride) Polymer Blends

Novel multifunctional biopolymer blend nanocomposites composed of poly(vinylidene fluoride)(PVDF) and tungsten disulfide nanotubes (INT-WS2) that are layered transition metal dichalcogenides (TMDCs) were easily prepared by applying an economical, scalable, and versatile melt processing route. Furthermore, their synergistic effect to enhance the properties of poly(L-lactic acid) (PLLA) matrix was investigated. From morphological analysis, it was shown that the incorporation of 1D (INT)-WS2 into the immiscible PLLA/PVDF mixtures (weight ratios: 80/20, 60/40, 40/60, and 20/80) led to an improvement in the dispersibility of the PVDF phase, a reduction in its average domain size, and consequently a larger interfacial area. In addition, the nanoparticles INT-WS2 can act as effective nucleating agents and reinforcing fillers in PLLA/PVDF blends, and as such, greatly improve their thermal and dynamic-mechanical properties. The improvements are more pronounced in the ternary blend nanocomposites with the lowest PVDF content, likely due to a synergistic effect of both highly crystalline PVDF and 1D-TMDCs nano-additives on the matrix performance. Considering the promising properties of the developed materials, the inexpensive synthetic process, and the extraordinary properties of environmentally friendly and biocompatibe 1D-TMDCs WS2, this work may open up opportunities to produce new PLLA/PVDF hybrid nanocomposites that show great potential for biomedical applications.
The effects of ingestion of hydrogen-dissolved alkaline electrolyzed water on stool consistency and gut microbiota: a double-blind randomized trial

A relationship between Bifidobacterium and defecation has previously been reported. Our hypothesis on the effectiveness of alkaline electrolyzed water (AEW) proposes that ingestion of AEW, considered possessing antioxidative properties, increases the number of Bifidobacteria and improves stool hardness and gastrointestinal symptoms. A double-blind, randomized study was conducted to evaluate the connection between stool consistency and change in gut microbiota composition induced by drinking hydrogen-dissolved AEW. The participants drank 500 mL of purified tap water or AEW every day for 2 weeks. In this study, drinking AEW did not drastically change gut microbiota, but it appeared to act on a specific bacterial species. Drinking AEW was confirmed to cause an increase in Bifidobacterium. The AEW group also saw stool consistency significantly converge to Bristol stool scale Type 4 (“normal”). Therefore, it is highly likely that the gut microbiota will be changed by drinking AEW. This study was retrospectively registered in University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: UMIN000039507) on February 18, 2020, and was approved by the Ethics Committee of University of Yamanashi (approval No. H30-25) on January 9, 2018.
Transcriptional Profiling of Cardiac Cells Links Age-Dependent Changes in Acetyl-CoA Signaling to Chromatin Modifications

Metabolism has emerged as a regulator of core stem cell properties such as proliferation, survival, self-renewal, and multilineage potential. Metabolites serve as secondary messengers, fine-tuning signaling pathways in response to microenvironment alterations. Studies show a role for central metabolite acetyl-CoA in the regulation of chromatin state through changes in histone acetylation. Nevertheless, metabolic regulators of chromatin remodeling in cardiac cells in response to increasing biological age remains unknown. Previously, we identified novel cardiac-derived stem-like cells (CTSCs) that exhibit increased functional properties in the neonatal heart (nCTSC). These cells are linked to a unique metabolism which is altered with CTSC aging (aCTSC). Here, we present an in-depth, RNA-sequencing-based (RNA-Seq) bioinformatic with cluster analysis that details a distinct epigenome present in nCTSCs but not in aCTSCs. Gene Ontology (GO) and pathway enrichment reveal biological processes, including metabolism, gene regulation enriched in nCTSCs, and STRING analysis that identifies a network of genes related to acetyl-CoA that can potentially influence chromatin remodeling. Additional validation by Western blot and qRT-PCR shows increased acetyl-CoA signaling and histone acetylation in nCTSCs compared to aCTSCs. In conclusion, our data reveal that the link between metabolism and histone acetylation in cardiac cells is altered with the aging of the cardiac tissue.
Dementia in people with severe or profound intellectual (and multiple) disabilities: Focus group research into relevance, symptoms and training needs

Abstract Background Differentiating dementia from baseline level of functioning is difficult among people with severe/profound intellectual (and multiple) disabilities. Moreover, studies on observable dementia symptoms are scarce. This study examined (a) the relevance of dementia diagnosis, (b) observable symptoms and (c) training/information needs. Methods Four explorative focus groups were held with care professionals and family members who have experience with people with severe/profound intellectual (and multiple) disabilities (≥40 years) and decline/dementia. Results Thematic analysis showed that participants wanted to know about a dementia diagnosis for a better understanding and to be able to make informed choices (question 1). Using a categorisation matrix, cognitive and behavioural changes were shown to be most prominent (question 2). Participants indicated that they needed enhanced training, more knowledge development and translation, and supportive organisational choices/policies (question 3). Conclusions Timely identifying/diagnosing dementia allows for a timely response to changing needs. This requires a better understanding of symptoms.
Clinical efficacy of T-cell therapy after short-term BRAF-inhibitor priming in patients with checkpoint inhibitor-resistant metastatic melanoma

Purpose Despite impressive response rates following adoptive transfer of autologous tumor-infiltrating lymphocytes (TILs) in patients with metastatic melanoma, improvement is needed to increase the efficacy and broaden the applicability of this treatment. We evaluated the use of vemurafenib, a small-molecule BRAF inhibitor with immunomodulatory properties, as priming before TIL harvest and adoptive T cell therapy in a phase I/II clinical trial. Methods 12 patients were treated with vemurafenib for 7 days before tumor excision and during the following weeks until TIL infusion. TILs were grown from tumor fragments, expanded in vitro and reinfused to the patient preceded by a lymphodepleting chemotherapy regimen and followed by interleukin-2 infusion. Extensive immune monitoring, tumor profiling and T cell receptor sequencing were performed. Results No unexpected toxicity was observed, and treatment was well tolerated. Of 12 patients, 1 achieved a complete response, 8 achieved partial response and 3 achieved stable disease. A PR and the CR are ongoing for 23 and 43 months, respectively. In vitro anti-tumor reactivity was found in TILs from 10 patients, including all patients achieving objective response. Serum and tumor biomarker analyses indicate that baseline cytokine levels and the number of T cell clones may predict response to TIL therapy. Further, TCR sequencing suggested skewing of TCR repertoire during in vitro expansion, promoting certain low frequency clonotypes. Conclusions Priming with vemurafenib before infusion of TILs was safe and feasible, and induced objective clinical responses in this cohort of patients with checkpoint inhibitor-resistant metastatic melanoma. In this trial, vemurafenib treatment seemed to decrease attrition and could be considered to bridge the waiting time while TILs are prepared.