Miracle-dz/UniFAR-FTUs huggingface dataset:
on Dietary Reference Values for phosphorus

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies derived Dietary Reference Values (DRVs) for phosphorus. The Panel considered data from balance studies, losses of phosphorus from the body and intestinal absorption for possible use in a factorial approach, and studies on phosphorus intake and long-term health outcomes. The Panel concluded that these data were insufficient for setting DRVs for phosphorus. Data on the calcium to phosphorus ratio in bones of healthy adults, adjusted for the proportion of phosphorus found outside bone, and data on whole-body calcium and phosphorus contents in Caucasian adults indicate that the calcium to phosphorus molar ratio in the body ranges from 1.4:1 to 1.9:1. Although the fractional absorption of phosphorus is higher than that of calcium, the Panel considered that the actual amounts of calcium and phosphorus that are available for absorption from the diet cannot be determined; therefore, the whole-body calcium to phosphorus ratio was used to set DRVs. The data were considered insufficient to derive Average Requirements and Population Reference Intakes. Based on the DRVs for calcium and considering a molar calcium to phosphorus ratio of 1.4:1 to 1.9:1, amounts of phosphorus were calculated. The Panel chose the lower bound of this range (a ratio of 1.4:1, which results in a higher phosphorus intake value) for setting an Adequate Intake (AI), taking into account estimated phosphorus intakes in Western countries, which are considerably higher than the values calculated. The AI is 160 mg/day for infants (7–11 months) and between 250 and 640 mg/day for children. For adults, the AI is 550 mg/day. Taking into consideration adaptive changes in phosphorus metabolism that occur during pregnancy and lactation, it was considered that the AI for adults also applies to pregnant and lactating women. © European Food Safety Authority, 2015
A Survey on Big Data and Hadoop Ecosystem Components

Big data describes techniques and technologies to store, distribute, manage, analyse large size of data set with high velocity. Here this paper is effort to present the basic understanding of the big data and its usefulness to an organization from the performance, also evaluate the challenges faced by a small organization. Hadoop is popular tool for big data implementation. Hadoop is the core platform for structuring Big Data, and solves the problem of making it useful for analytics purposes. Hadoop and HDFS by Apache are widely used for strong and managing data. Hadoop is the platform for structuring big data and solves the problem of making it useful for analytic purpose. This paper is dealt with big data challenges, hadoop components and problem with hadoop were described in detail.
Valutazione di costo-efficacia di ponatinib nella terapia della leucemia mieloide cronica in Italia

50% probability when compared to the lower value (90% probability when compared with the higher). This analysis suggests that treating CML-CP with ponatinib provides a substantial clinical benefit as compared with current alternatives, with an incremental survival of 3-4 QALYs and at reasonable costs from the perspective of the Italian NHS. Sensitivity analysis confirmed the robustness of these results.
Oxytocin and serotonin in the modulation of neural function: Neurobiological underpinnings of autism-related behavior

Autism spectrum disorders (ASD) is a group of generalized neurodevelopmental disorders. Its main clinical features are social communication disorder and repetitive stereotyped behavioral interest. The abnormal structure and function of brain network is the basis of social dysfunction and stereotyped performance in patients with autism spectrum disorder. The number of patients diagnosed with ASD has increased year by year, but there is a lack of effective intervention and treatment. Oxytocin has been revealed to effectively improve social cognitive function and significantly improve the social information processing ability, empathy ability and social communication ability of ASD patients. The change of serotonin level also been reported affecting the development of brain and causes ASD-like behavioral abnormalities, such as anxiety, depression like behavior, stereotyped behavior. Present review will focus on the research progress of serotonin and oxytocin in the pathogenesis, brain circuit changes and treatment of autism. Revealing the regulatory effect and neural mechanism of serotonin and oxytocin on patients with ASD is not only conducive to a deeper comprehension of the pathogenesis of ASD, but also has vital clinical significance.
Diversity and composition of soil bacteria between abandoned and selective-farming farmlands in an antimony mining area

Background and aims Land abandonment and selective farming are two common management methods to restore the soil conditions of low-pollution farmland in mining areas. The soil bacterial community plays an important role in farmland soil restoration; however, few studies have compared the composition and diversity of soil bacteria between the abandoned farmlands (AFS) and selective-farming farmlands (FFS). Here, the effects of AFS and FFS on soil properties and bacterial diversity were evaluated in an antimony (Sb) mining area in southern China. This study aimed to identify effective land management methods in terms of positive or negative changes in soil environment and bacterial diversity. Methods 16S rRNA high-throughput sequencing was used to compare the diversity and composition of soil bacteria between AFS and FFS in the Xikuangshan (the largest Sb mine in the world). Results Compared to AFS, FFS had higher Sb concentration and nutritional properties (e.g., available N, P, and K) and lower Zn concentration (p < 0.05). The bacterial alpha diversity including Chao1 index, Simpson index, Shannon index and Pielou−e index in FFS was higher than AFS (p < 0.05). At the phylum level, FFS had higher relative abundances of Chloroflexi, Acidobacteria, Gemmatimonadetes, and Rokubacteria, and lower relative abundances of Firmicutes, Actinobacteria, and Bacteroidetes. At the genus level, FFS had higher relative abundances of Acidothermus, Haliangium, and Rokubacteriales, and lower relative abundances of Bacillus, Rhodococcus, Sphingomonas, and 67-14. Redundancy analysis indicated that soil heavy metal content and soil fertility were closely correlated with the soil bacterial community. Altogether, selective farming of low-pollution farmland in the mining area can improve soil properties and soil bacterial diversity.
Stress-related expression of the chloroplast EGY3 pseudoprotease and its possible impact on chloroplasts’ proteome composition

The EGY3 is a pseudoprotease, located in the thylakoid membrane, that shares homology with the family of site-2-proteases (S2P). Although S2P proteases are present in the cells of all living organisms, the EGY3 was found only in plant cells. The sequence of the pseudoprotease is highly conserved in the plant kingdom; however, little is known about its physiological importance. Results obtained with real-time PCR indicated that the expression of the EGY3 gene is dramatically induced during the first few hours of exposure to high light and high-temperature stress. The observed increase in transcript abundance correlates with protein accumulation level, which indicates that EGY3 participates in response to both high-temperature and high light stresses. The lack of the pseudoprotease leads, in both stresses, to lower concentrations of hydrogen peroxide. However, the decrease of chloroplast copper/zinc superoxide dismutase 2 level was observed only during the high light stress. In both analyzed stressful conditions, proteins related to RubisCO folding, glycine metabolism, and photosystem I were identified as differently accumulating in egy3 mutant lines and WT plants; however, the functional status of PSII during analyzed stressful conditions remains very similar. Our results lead to a conclusion that EGY3 pseudoprotease participates in response to high light and high-temperature stress; however, its role is associated rather with photosystem I and light-independent reactions of photosynthesis.
Availability and Affordability of Oncology Drugs in 2012-2021 in China and the United States

Objective To systematically summarize the landscape and characteristics of all approved new anticancer drugs for the last 10 years in China and the United States (US) to further inform the trend, current state, and existing gap in the availability and affordability of cancer medicine between the two countries. Methods Mainly based on the Pharmcube database, a list and detailed information of anticancer drugs approved in China and the United States were acquired. The annual number, time lag, and basic characteristics, including drug type, mechanism, enterprise type, indication population, drug target, and cancer type of approved drugs were compared. Results Eighty-seven and 118 new anticancer drugs were approved in China and the US, respectively, showing a stable trend in the US, while a significant increase was observed after 2016 in China. Of the 42 cancer medicines launched in both countries, the US took precedence, and the median time lag markedly decreased, from 6.53 years in 2012 to 0.88 years in 2020. A total of 14.4% of drugs were applicable to children in the US, while only 2.3% were applicable in China, and there was no difference in drug type and enterprise. Thirty-one and 43 targets were explored, with respect to 27 and 36 cancer types in China and the US, respectively, during the period. In addition, the expenditure of drugs on PD-1 and PD-L1 in China was generally lower than that in America. Conclusion The availability of new anticancer drugs has increased dramatically in the past decade, particularly in China. Compared with the US, the launch of new anticancer drugs in China lags behind, but the time lag has been shortened significantly, and better affordability is observed in immune drugs. More attention should be given to differentiated innovation, and unmet medical needs in special populations like childhood tumors, which are important directions of new drug R&D in China.
Recombinant Listeria ivanovii strain expressing listeriolysin O in place of ivanolysin O might be a potential antigen carrier for vaccine construction

Listeria monocytogenes (LM) induces efficient and specific T-cell immune responses in the host. Listeriolysin O (LLO) is the main virulence protein of LM. LLO helps LM escape from the lysosome. However, the pronounced pathogenicity of LM limits its practical application as a live bacterial vector. Listeria ivanovii (LI) also displays intracellular parasitic abilities, cell to cell transfer, and other LM properties, with an elevated biosafety relative to LM. We have confirmed that LI can be used as a viable bacterial vaccine vector. However, we have also observed in vivo that LI vector vaccine candidates survive in the immune organ (spleen) for a shorter time compared with the survival time of LM and elicit weaker immune responses compared with LM. Studies have confirmed that hemolysin correlates with some important biological properties of Listeria, including cell invasion, intracellular proliferation, and the ability to induce immune responses. We speculated that the weaker immunogenicity of LI compared to LM may be related to the function of ivanolysin O (ILO). Here, we established a hemolysin gene deletion strain, LIΔilo, and a modified strain, LIΔilo:hly, whose ilo was replaced by hly. The hemolysin-modified strain was attenuated; however, it led to significantly improved invasive and proliferative activities of antigen-presenting cells, including those of RAW 264.7 macrophages, compared with the effects of LI. Mice immunized twice with LIΔilo:hly showed higher cytokine levels and better challenge protection rates than LI-immunized mice. This is the first description in Listeria carrier vaccine research of the modification of LI hemolysin to obtain a better vaccine carrier than LI. The recombinant strain LIΔilo:hly showed good biosafety and immunogenicity, and thus appears to be a good vector strain for vaccine development.
Role of Gut Microbiome in Autism Spectrum Disorder and Its Therapeutic Regulation

Autism spectrum disorder (ASD) is a neurological disorder that affects normal brain development. The recent finding of the microbiota–gut–brain axis indicates the bidirectional connection between our gut and brain, demonstrating that gut microbiota can influence many neurological disorders such as autism. Most autistic patients suffer from gastrointestinal (GI) symptoms. Many studies have shown that early colonization, mode of delivery, and antibiotic usage significantly affect the gut microbiome and the onset of autism. Microbial fermentation of plant-based fiber can produce different types of short-chain fatty acid (SCFA) that may have a beneficial or detrimental effect on the gut and neurological development of autistic patients. Several comprehensive studies of the gut microbiome and microbiota–gut–brain axis help to understand the mechanism that leads to the onset of neurological disorders and find possible treatments for autism. This review integrates the findings of recent years on the gut microbiota and ASD association, mainly focusing on the characterization of specific microbiota that leads to ASD and addressing potential therapeutic interventions to restore a healthy balance of gut microbiome composition that can treat autism-associated symptoms.
Quantitative Comparison of Breast Cancer Resistance Protein (BCRP/ABCG2) Expression and Function Between Maternal Blood-Brain Barrier and Placental Barrier in Mice at Different Gestational Ages

Breast cancer resistance protein (BCRP) is expressed by brain capillary endothelial cells and at the interface between two placental syncytiotrophoblast layers in rodents and serves to suppress drug distribution to the brain and the fetus. The purpose of the present study is to determine and compare the apparent impact of a single BCRP molecule on drug transfer between the maternal blood-brain barrier and placental barrier in pregnant mice at different gestation ages. BCRP protein was quantified by liquid chromatography-tandem mass spectrometry. Genistein or dantrolene was continuously administered to pregnant Bcrp −/− or wild-type (WT) mice, and the brain-to-plasma concentration ratio in the mother (K p,brain) and the fetal-to-maternal ratio of plasma concentrations (K p,fp) were determined. At gestational day 15.5 (GD15.5), the protein amount of BCRP at the murine placental barrier was estimated to be approximately three times higher than at the maternal blood-brain barrier, but the levels were approximately the same at GD17.5 due to the decline of placental BCRP expression during gestation. On the other hand, the values of Bcrp −/−/WT ratio of K p,brain for genistein and dantrolene were 6.1 and 3.8, respectively, while the K p,fp ratios were all less than 2.0. These results indicate that the apparent impact of a single placental BCRP molecule on the restriction of drug distribution is much less than that of a single brain BCRP molecule, probably because the function of placental BCRP is attenuated by bypass transfer through the connexin26 gap junctions between adjacent syncytiotrophoblast layers. The present study also found that the expression amount of BCRP protein at the human placental barrier formed by the monolayer of syncytiotrophoblasts was lower than that in mice, but this species difference appears to be functionally compensated by the murine-specific bypass route through gap junctions, at least in part.
Higher dietary inflammatory index is associated with increased all-cause mortality in adults with chronic kidney disease

Background Diet property grounded on inflammatory potential, evaluated by the dietary inflammatory index (DII), has been proven to be connected with mortality, while studies of adults with chronic kidney disease (CKD) are scarce. Objective The purpose of this research was to evaluate the interrelationships between DII and all-cause mortality among adults with CKD. Methods In the National Health and Nutrition Examination Survey (NHANES) 2001–2006, we identified and evaluated data of 4,554 adults with CKD. DII scores were calculated from 24 h of dietary consumption at baseline. Vital status was followed through 31 December 2015. The association of all-cause mortality with DII score was assessed using the Kaplan–Meier curve and the Cox regression analysis. Results After an average follow-up of 132.103 months, a total of 1,246 (27.36%) deaths were recorded. The death rates in the DII tertile categories were 24.04, 26.81, and 31.23%, respectively. The Kaplan–Meier curve showed increased death risks for the high DII tertile as compared with the low DII tertile. After we adjusted for a broad range of possible confounders, the estimation between extreme tertiles of DII scores presented a positive and significant association with all-cause mortality [hazard ratio (HR): 1.21, 95% CI: 1.05–1.39]. Conclusion Our results confirm the hypothesis that proinflammatory diets contribute to the increased all-cause mortality in adults with CKD.
NKCC1 and KCC2: Structural insights into phospho-regulation

Inhibitory neurotransmission plays a fundamental role in the central nervous system, with about 30–50% of synaptic connections being inhibitory. The action of both inhibitory neurotransmitter, gamma-aminobutyric-acid (GABA) and glycine, mainly relies on the intracellular Cl– concentration in neurons. This is set by the interplay of the cation chloride cotransporters NKCC1 (Na+, K+, Cl– cotransporter), a main Cl– uptake transporter, and KCC2 (K+, Cl– cotransporter), the principle Cl– extruder in neurons. Accordingly, their dysfunction is associated with severe neurological, psychiatric, and neurodegenerative disorders. This has triggered great interest in understanding their regulation, with a strong focus on phosphorylation. Recent structural data by cryogenic electron microscopy provide the unique possibility to gain insight into the action of these phosphorylations. Interestingly, in KCC2, six out of ten (60%) known regulatory phospho-sites reside within a region of 134 amino acid residues (12% of the total residues) between helices α8 and α9 that lacks fixed or ordered three-dimensional structures. It thus represents a so-called intrinsically disordered region. Two further phospho-sites, Tyr903 and Thr906, are also located in a disordered region between the ß8 strand and the α8 helix. We make the case that especially the disordered region between helices α8 and α9 acts as a platform to integrate different signaling pathways and simultaneously constitute a flexible, highly dynamic linker that can survey a wide variety of distinct conformations. As each conformation can have distinct binding affinities and specificity properties, this enables regulation of [Cl–]i and thus the ionic driving force in a history-dependent way. This region might thus act as a molecular processor underlying the well described phenomenon of ionic plasticity that has been ascribed to inhibitory neurotransmission. Finally, it might explain the stunning long-range effects of mutations on phospho-sites in KCC2.
The role of the Pseudomonas aeruginosa hypermutator phenotype on the shift from acute to chronic virulence during respiratory infection

Chronic respiratory infection (CRI) with Pseudomonas aeruginosa (Pa) presents many unique challenges that complicate treatment. One notable challenge is the hypermutator phenotype which is present in up to 60% of sampled CRI patient isolates. Hypermutation can be caused by deactivating mutations in DNA mismatch repair (MMR) genes including mutS, mutL, and uvrD. In vitro and in vivo studies have demonstrated hypermutator strains to be less virulent than wild-type Pa. However, patients colonized with hypermutators display poorer lung function and a higher incidence of treatment failure. Hypermutation and MMR-deficiency create increased genetic diversity and population heterogeneity due to elevated mutation rates. MMR-deficient strains demonstrate higher rates of mucoidy, a hallmark virulence determinant of Pa during CRI in cystic fibrosis patients. The mucoid phenotype results from simple sequence repeat mutations in the mucA gene made in the absence of functional MMR. Mutations in Pa are further increased in the absence of MMR, leading to microcolony biofilm formation, further lineage diversification, and population heterogeneity which enhance bacterial persistence and host immune evasion. Hypermutation facilitates the adaptation to the lung microenvironment, enabling survival among nutritional complexity and microaerobic or anaerobic conditions. Mutations in key acute-to-chronic virulence “switch” genes, such as retS, bfmS, and ampR, are also catalyzed by hypermutation. Consequently, strong positive selection for many loss-of-function pathoadaptive mutations is seen in hypermutators and enriched in genes such as lasR. This results in the characteristic loss of Pa acute infection virulence factors, including quorum sensing, flagellar motility, and type III secretion. Further study of the role of hypermutation on Pa chronic infection is needed to better inform treatment regimens against CRI with hypermutator strains.
Loss of coastal ecosystem services in Mexico: An approach to economic valuation in the face of sea level rise

The economic valuation of coastal ecosystem services is a critical step for the design of sound public policies that support the preservation of the services that nature provides to society in the context of climate change. Using the value transfer method, we obtained the economic valuation that represents the loss of coastal ecosystem services caused by sea level rise in Mexico. Using the Bathtub method, digital elevation models and sea level data, we identified the areas in the country prone to flooding and the associated ecosystem impacts. In Mexico, the annual economic loss caused by the disappearance of coastal ecosystem services is estimated at $6,476,402,405 USD, where wetlands represent the greatest economic losses, since they represent the largest affected ecosystem by area. However, beaches and dunes are the most valued ecosystem due to the economic activities that occur in these areas. In the mangroves, the service as habitat, refuge and nursery is the most valued for its positive relationship with fisheries. The states with the most economic losses are Baja California Sur, Sinaloa and Campeche. The protection of the coastal zone in Mexico should be a priority in the development strategies in the country because its loss and/or rehabilitation imply high economic costs and compromises the wellbeing of society.