Miracle-dz/UniFAR-FTUs huggingface dataset:
Iron biofortification interventions to improve iron status and functional outcomes

This analysis was conducted to evaluate the evidence of the efficacy of iron biofortification interventions on iron status and functional outcomes. Iron deficiency is a major public health problem worldwide, with a disproportionate impact on women and young children, particularly those living in resource-limited settings. Biofortification, or the enhancing of micronutrient content in staple crops, is a promising and sustainable agriculture-based approach to improve nutritional status. Previous randomised efficacy trials and meta-analyses have demonstrated that iron-biofortification interventions improved iron biomarkers; however, no systematic reviews to date have examined the efficacy of biofortification interventions on health outcomes. We conducted a systematic review of the efficacy of iron-biofortified staple crops on iron status and functional outcomes: cognitive function (e.g. attention, memory) and physical performance. Five studies from three randomised efficacy trials (i.e. rice, pearl millet, beans) conducted in the Philippines, India and Rwanda were identified for inclusion in this review. Iron status (Hb, serum ferritin, soluble transferrin receptor, total body iron, α-1-acid glycoprotein) was measured at baseline and endline in each trial; two studies reported cognitive outcomes, and no studies reported other functional outcomes. Meta-analyses were conducted using DerSimonian and Laird random-effects methods. Iron-biofortified crop interventions significantly improved cognitive performance in attention and memory domains, compared with conventional crops. There were no significant effects on categorical outcomes such as iron deficiency or anaemia. Further studies are needed to determine the efficacy of iron-biofortified staple crops on human health, including additional functional outcomes and other high-risk populations.
Whole Genome Sequencing of A(H3N2) Influenza Viruses Reveals Variants Associated with Severity during the 2016–2017 Season

Influenza viruses cause a remarkable disease burden and significant morbidity and mortality worldwide, and these impacts vary between seasons. To understand the mechanisms associated with these differences, a comprehensive approach is needed to characterize the impact of influenza genomic traits on the burden of disease. During 2016–2017, a year with severe A(H3N2), we sequenced 176 A(H3N2) influenza genomes using next generation sequencing (NGS) for routine surveillance of circulating influenza viruses collected via the French national influenza community-based surveillance network or from patients hospitalized in the intensive care units of the University Hospitals of Lyon, France. Taking into account confounding factors, sequencing and clinical data were used to identify genomic variants and quasispecies associated with influenza severity or vaccine failure. Several amino acid substitutions significantly associated with clinical traits were found, including NA V263I and NS1 K196E which were associated with severity and co-occurred only in viruses from the 3c.2a1 clade. Additionally, we observed that intra-host diversity as a whole and on a specific set of gene segments increased with severity. These results support the use of whole genome sequencing as a tool for the identification of genetic traits associated with severe influenza in the context of influenza surveillance.
Dynamics of Human Gut Microbiota and Short-Chain Fatty Acids in Response to Dietary Interventions with Three Fermentable Fibers

These results reveal that not all fermentable fibers are equally capable of stimulating SCFA production, and they highlight the importance of the composition of an individual’s microbiota in determining whether or not they respond to a specific dietary supplement. In particular, R. bromii or C. chartatabidum may be required for enhanced butyrate production in response to RS. Bifidobacteria, though proficient at degrading RS and inulin, may not contribute to the butyrogenic effect of those fermentable fibers in the short term. ABSTRACT Production of short-chain fatty acids (SCFAs), especially butyrate, in the gut microbiome is required for optimal health but is frequently limited by the lack of fermentable fiber in the diet. We attempted to increase butyrate production by supplementing the diets of 174 healthy young adults for 2 weeks with resistant starch from potatoes (RPS), resistant starch from maize (RMS), inulin from chicory root, or an accessible corn starch control. RPS resulted in the greatest increase in total SCFAs, including butyrate. Although the majority of microbiomes responded to RPS with increases in the relative abundance of bifidobacteria, those that responded with an increase in Ruminococcus bromii or Clostridium chartatabidum were more likely to yield higher butyrate concentrations, especially when their microbiota were replete with populations of the butyrate-producing species Eubacterium rectale. RMS and inulin induced different changes in fecal communities, but they did not generate significant increases in fecal butyrate levels. IMPORTANCE These results reveal that not all fermentable fibers are equally capable of stimulating SCFA production, and they highlight the importance of the composition of an individual’s microbiota in determining whether or not they respond to a specific dietary supplement. In particular, R. bromii or C. chartatabidum may be required for enhanced butyrate production in response to RS. Bifidobacteria, though proficient at degrading RS and inulin, may not contribute to the butyrogenic effect of those fermentable fibers in the short term.
Killer Immunoglobulin-Like Receptor 2DS2 (KIR2DS2), KIR2DL2-HLA-C1, and KIR2DL3 as Genetic Markers for Stratifying the Risk of Cytomegalovirus Infection in Kidney Transplant Recipients

Infection with cytomegalovirus (CMV) remains a major problem in kidney transplant recipients, resulting in serious infectious complications and occasionally mortality. Accumulating evidence indicates that natural killer cell immunoglobulin-like receptors (KIRs) and their ligands affect the susceptibility to various diseases, including viral infections (e.g., CMV infection). We investigated whether KIR genes and their ligands affect the occurrence of CMV infection in a group of 138 kidney transplant recipients who were observed for 720 days posttransplantation. We typed the recipients for the presence of KIR genes (human leukocyte antigen C1 [HLA-C1], HLA-C2, HLA-A, HLA-B, and HLA-DR1) by polymerase chain reaction with sequence-specific primers. The multivariate analysis revealed that the lack of KIR2DS2 (p = 0.035), the presence of KIR2DL3 (p = 0.075), and the presence of KIR2DL2–HLA-C1 (p = 0.044) were risk factors for posttransplant CMV infection. We also found that a lower estimated glomerular filtration rate (p = 0.036), an earlier time of antiviral prophylaxis initiation (p = 0.025), lymphocytopenia (p = 0.012), and pretransplant serostatus (donor-positive/recipient-negative; p = 0.042) were independent risk factors for posttransplant CMV infection. In conclusion, our findings confirm that the KIR/HLA genotype plays a significant role in anti-CMV immunity and suggest the contribution of both environmental and genetic factors to the incidence of CMV infection after kidney transplantation.
Genetic Regulation of Neuronal Progranulin Reveals a Critical Role for the Autophagy-Lysosome Pathway

Deficient progranulin levels cause dose-dependent neurological syndromes: haploinsufficiency leads to frontotemporal lobar degeneration (FTLD) and nullizygosity produces adult-onset neuronal ceroid lipofuscinosis. Mechanisms controlling progranulin levels are largely unknown. To better understand progranulin regulation, we performed a genome-wide RNAi screen using an ELISA-based platform to discover genes that regulate progranulin levels in neurons. We identified 830 genes that raise or lower progranulin levels by at least 1.5-fold in Neuro2a cells. When inhibited by siRNA or some by submicromolar concentrations of small-molecule inhibitors, 33 genes of the druggable genome increased progranulin levels in mouse primary cortical neurons; several of these also raised progranulin levels in FTLD model mouse neurons. “Hit” genes regulated progranulin by transcriptional or posttranscriptional mechanisms. Pathway analysis revealed enrichment of hit genes from the autophagy–lysosome pathway (ALP), suggesting a key role for this pathway in regulating progranulin levels. Progranulin itself regulates lysosome function. We found progranulin deficiency in neurons increased autophagy and caused abnormally enlarged lysosomes and boosting progranulin levels restored autophagy and lysosome size to control levels. Our data link the ALP to neuronal progranulin: progranulin levels are regulated by autophagy and, in turn, progranulin regulates the ALP. Restoring progranulin levels by targeting genetic modifiers reversed FTLD functional deficits, opening up potential opportunities for future therapeutics development. SIGNIFICANCE STATEMENT Progranulin regulates neuron and immune functions and is implicated in aging. Loss of one functional allele causes haploinsufficiency and leads to frontotemporal lobar degeneration (FTLD), the second leading cause of dementia. Progranulin gene polymorphisms are linked to Alzheimer's disease (AD) and complete loss of function causes neuronal ceroid lipofuscinosis. Despite the critical role of progranulin levels in neurodegenerative disease risk, almost nothing is known about their regulation. We performed an unbiased screen and identified specific pathways controlling progranulin levels in neurons. Modulation of these pathways restored levels in progranulin-deficient neurons and reversed FTLD phenotypes. We provide a new comprehensive understanding of the genetic regulation of progranulin levels and identify potential targets to treat FTLD and other neurodegenerative diseases, including AD.
The effectiveness of noise interventions in the ICU.

PURPOSE OF REVIEW Excessive noise has direct adverse physiological and psychological effects, and may also have indirect negative health consequences by reducing sleep quality and quantity. This review presents a synthesis of the epidemiology of noise in the ICU, and the potential interventions designed to attenuate noise and protect patients. RECENT FINDINGS Noise increases cortisol release, oxygen consumption, and vasoconstriction. ICU noise levels are excessive throughout the 24-h cycle, irrespective of level of intervention or whether the patient is in a side room or open ward. Direct measurement suggests that noise is a substantial contributor to poor sleep quantity and quality in the ICU and is frequently recalled by survivors of critical illness as a negative experience of ICU admission. Noise abatement, environmental masking and pharmacological interventions may all reduce the impact of noise on patients. However, the sustainability of behavioural interventions remains uncertain and high-quality evidence demonstrating the benefit of any intervention on patient-centered outcomes is lacking. SUMMARY Noise levels in the ICU are consistently reported to reach levels likely to have both direct and indirect adverse health consequences for both patients and staff. Noise reduction, abating the transmission of noise and pharmacological modulation of the adverse neural effects of noise are all potentially beneficial strategies, although definitive evidence of improved patient-centered outcomes is lacking.
Excess early postnatal weight gain and blood pressure in healthy young children

Abstract Blood pressure (BP) tracks from childhood to adulthood, and early BP trajectories predict cardiovascular disease risk later in life. Excess postnatal weight gain is associated with vascular changes early in life. However, to what extent it is associated with children’s BP is largely unknown. In 853 healthy 5-year-old children of the Wheezing-Illnesses-Study-Leidsche-Rijn (WHISTLER) birth cohort, systolic (SBP) and diastolic BP (DBP) were measured, and z scores of individual weight gain rates adjusted for length gain rates were calculated using at least two weight and length measurements from birth until 3 months of age. Linear regression analyses were conducted to investigate the association between weight gain rates adjusted for length gain rates and BP adjusted for sex and ethnicity. Each standard deviation increase in weight gain rates adjusted for length gain rates was associated with 0.9 mmHg (95% CI 0.3, 1.5) higher sitting SBP after adjustment for confounders. Particularly in children in the lowest birth size decile, high excess weight gain was associated with higher sitting SBP values compared to children with low weight gain rates adjusted for length gain rates. BMI and visceral adipose tissue partly explained the association between excess weight gain and sitting SBP (β 0.5 mmHg, 95% CI −0.3, 1.3). Weight gain rates adjusted for length gain rates were not associated with supine SBP or DBP. Children with excess weight gain, properly adjusted for length gain, in the first three months of life, particularly those with a small birth size, showed higher sitting systolic BP at the age of 5 years.
Review of the impact of MALDI-TOF MS in public health and hospital hygiene, 2018

Introduction MALDI-TOF MS represents a new technological era for microbiology laboratories. Improved sample processing and expanded databases have facilitated rapid and direct identification of microorganisms from some clinical samples. Automated analysis of protein spectra from different microbial populations is emerging as a potential tool for epidemiological studies and is expected to impact public health. Aim To demonstrate how implementation of MALDI-TOF MS has changed the way microorganisms are identified, how its applications keep increasing and its impact on public health and hospital hygiene. Methods A review of the available literature in PubMED, published between 2009 and 2018, was carried out. Results Of 9,709 articles retrieved, 108 were included in the review. They show that rapid identification of a growing number of microorganisms using MALDI-TOF MS has allowed for optimisation of patient management through prompt initiation of directed antimicrobial treatment. The diagnosis of Gram-negative bacteraemia directly from blood culture pellets has positively impacted antibiotic streamlining, length of hospital stay and costs per patient. The flexibility of MALDI-TOF MS has encouraged new forms of use, such as detecting antibiotic resistance mechanisms (e.g. carbapenemases), which provides valuable information in a reduced turnaround time. MALDI-TOF MS has also been successfully applied to bacterial typing. Conclusions MALDI-TOF MS is a powerful method for protein analysis. The increase in speed of pathogen detection enables improvement of antimicrobial therapy, infection prevention and control measures leading to positive impact on public health. For antibiotic susceptibility testing and bacterial typing, it represents a rapid alternative to time-consuming conventional techniques.
Codon stabilization coefficient as a metric to gain insights into mRNA stability and codon bias and their relationships with translation

Abstract The codon stabilization coefficient (CSC) is derived from the correlation between each codon frequency in transcripts and mRNA half-life experimental data. In this work, we used this metric as a reference to compare previously published Saccharomyces cerevisiae mRNA half-life datasets and investigate how codon composition related to protein levels. We generated CSCs derived from nine studies. Four datasets produced similar CSCs, which also correlated with other independent parameters that reflected codon optimality, such as the tRNA abundance and ribosome residence time. By calculating the average CSC for each gene, we found that most mRNAs tended to have more non-optimal codons. Conversely, a high proportion of optimal codons was found for genes coding highly abundant proteins, including proteins that were only transiently overexpressed in response to stress conditions. We also used CSCs to identify and locate mRNA regions enriched in non-optimal codons. We found that these stretches were usually located close to the initiation codon and were sufficient to slow ribosome movement. However, in contrast to observations from reporter systems, we found no position-dependent effect on the mRNA half-life. These analyses underscore the value of CSCs in studies of mRNA stability and codon bias and their relationships with protein expression.
Effects of thrombolysis within 6 hours on acute cerebral infarction in an improved rat embolic middle cerebral artery occlusion model for ischaemic stroke

Recombinant tissue plasminogen activator (rt‐PA) is the first‐line drug for revascularization in acute cerebral infarction (ACI) treatment. In this study, an improved rat embolic middle cerebral artery occlusion model for ischaemic stroke was used and the rats were killed on the first, third and seventh day after model establishment. Increases in infarct volume were significantly less in the thrombolytic group than in the conventional group at every time‐point. The microvascular density (MVD) in the thrombolytic group was significantly higher than that in the conventional group at every time‐point, especially on the seventh day. Increases in the expressions of neuronal nitric‐oxide synthase (NOS) and caspase‐3 in the ischaemic region and in the nitric oxide contents, malondialdehyde contents, and inducible NOS activities in the cortex of infarct side were significantly less in the thrombolytic group than in the conventional group. Furthermore, decreases in the superoxide dismutase activities in the thrombolytic group were significantly less than those in the conventional group. In conclusion, thrombolytic rt‐PA therapy within a broadened therapeutic window (6 hours) could significantly decrease the infarct volume after ACI, possibly by increasing MVD in the ischaemic region, decreasing apoptotic molecule expression, and alleviating the oxidative stress response.
Shared and differential features of Robo3 expression pattern in amniotes

In Bilaterians, commissural neurons project their axons across the midline of the nervous system to target neurons on the opposite side. In mammals, midline crossing at the level of the hindbrain and spinal cord requires the Robo3 receptor which is transiently expressed by all commissural neurons. Unlike other Robo receptors, mammalian Robo3 receptors do not bind Slit ligands and promote midline crossing. Surprisingly, not much is known about Robo3 distribution and mechanism of action in other vertebrate species.
Efecto in vitro del aceite esencial de los frutos de Caesalpinia spinosa (molina) Kuntze, tara sobre la viabilidad de cultivos de Staphylococcus aureus meticilino resistente

Se han evaluado, con resultados positivos, extractos de legumbres de Cesalpinia spinosa(Molina) Kuntze, tara, especie vegetal nativa del Peru, contra microorganismos procariotas (bacterias)y eucariotas (hongos). En el presente estudio se decidio utilizar aceite esencial, a fin de evaluar su efecto in vitro sobre la viabilidad de Staphylococcus aureus meticilino resistente(SARM) y a la vez determinar las CMIs y CMBs. De legumbres secas de tara se obtuvo aceite esencial, el que se extrajo por medio del sistema de hidrodestilacion. Fueron evaluadas S. aureusATCC 25923, cepa sensible y la cepa SARMATCC 43300, el cultivo SARM HRDT347 por medio de la prueba de difusion en agar y excavado en placa, asi como con la de dilucion en caldo. Para determinar las CMIs y las CMBs, las diluciones utilizadas de aceite esencial de tara fueron 5, 2.5, 1.25, 0.625, 0.312, 0.156, 0.078, 0.039,0.019 y 0.009 % respectivamente. Los resultados nos permitieron llegar a las siguientes conclusiones: existe efecto inhibitorio del aceite esencial tara sobre la viabilidad de cultivos SARM; las CMIs para S. aureus ATCC43300 y HRDT347 son similares, es decir, son del orden del 0.156% del aceite esencial, mientras que para S. aureus ATCC 25923 es 0.039%;las CMBs para S. aureus ATCC 4330 y HRDT347 son similares , es decir, son del orden del 0.312% del aceite esencial, mientras que para S. aureus ATCC 25923 es 0.156% Palabras clave: SARM, tara, efecto antimicrobiano,CMI, CMB.
Minocycline and the risk of acute psychiatric events in adolescence: A self-controlled case series

Background Minocycline has neurological anti-inflammatory properties and has been hypothesised to have antipsychotic effects. Aim The aim of this study was to investigate, using routinely collected United Kingdom primary health care data, whether adolescent men and women are more or less likely to receive an urgent psychiatric referral during treatment for acne with minocycline compared with periods of non-treatment. Method A self-controlled case series using United Kingdom Clinical Practice Research Datalink to calculate the incidence rate ratio of urgent psychiatric referrals for individuals, comparing periods during which minocycline was prescribed with unexposed periods, adjusted for age. Results We found 167 individuals who were at the time exposed to minocycline for a mean of 99 days and who received an urgent psychiatric referral. There was no difference in psychiatric referral risk during periods of exposure compared with periods of non-exposure: incidence rate ratio first 6 weeks of exposure 1.96, 95% confidence interval 0.82–4.71, p=0.132; incidence rate ratio remaining exposure period=1.97, 95% confidence interval 0.86–4.47, p=0.107. Conclusions We found no evidence in support of a protective effect of minocycline against severe psychiatric symptoms in adolescence.
Deceleration, Acceleration, and Impacts Are Strong Contributors to Muscle Damage in Professional Australian Football.

Gastin, PB, Hunkin, SL, Fahrner, B, and Robertson, S. Deceleration, acceleration, and impacts are strong contributors to muscle damage in professional Australian football. J Strength Cond Res XX(X): 000-000, 2019-The purpose of this study was to investigate the relationships between serum creatine kinase [CK], an indirect marker of muscle damage, and specific indices of match load in elite Australian football. Twenty-six professional players were assessed during a competitive Australian Football League (AFL) season. [CK] was collected 24-36 hours before match and 34-40 hours after match during 8 in-season rounds. An athlete-tracking technology was used to quantify match load. Generalized estimating equations and random forest models were constructed to determine the extent to which match-load indices and pre-match [CK] explained post-match [CK]. There was a 129 ± 152% increase in [CK] in response to AFL competition. Generalized estimating equations found that number of impacts >3g (p = 0.004) and game time (p = 0.016) were most strongly associated with post-match [CK]. Random forest, with considerably lower errors (130 vs. 316 U·L), found deceleration, acceleration, impacts >3g, and sprint distance to be the strongest predictors. Pre-match [CK] accounted for 11% of post-match [CK], and considerable interindividual and intraindividual variability existed in the data. Creatine kinase, an indicator of muscle damage, was considerably elevated as a result of AFL competition. Parametric and machine-learning analysis techniques found several indices of physical load associated with muscle damage during competition, with impacts >3g and high-intensity running variables as the strongest predictors. [CK] may be used as a global measure of muscle damage in field team sports such as AF, yet with some caution given cost, invasiveness, and inherent variability. Quantifying physical load and the responses to that load can guide athlete management decision-making and is best undertaken within a suite of practical, sport-specific measures, where data are interpreted individually and with an understanding of the limitations.