Miracle-dz/UniFAR-FTUs huggingface dataset:
Nutritional adequacy of goat milk infant formulas for term infants: a double-blind randomised controlled trial

The safety and nutritional adequacy of goat milk infant formulas have been questioned. The primary aim of the present study was to compare the growth and nutritional status of infants fed a goat milk infant formula with those of infants fed a typical whey-based cow milk infant formula. The secondary aim was to examine a range of health- and allergy-related outcomes. A double-blind, randomised controlled trial with 200 formula-fed term infants randomly assigned to receive either goat or cow milk formula from 2 weeks to at least 4 months of age was conducted. A cohort of 101 breast-fed infants was included for comparison. Weight, length and head circumference were measured at 2 weeks and 1, 2, 3, 4, 6 and 12 months of age. Nutritional status was assessed from serum albumin, urea, creatinine, Hb, ferritin, and folate and plasma amino acid concentrations at 4 months. Z-scores for weight, length, head circumference and weight for length were not different between the two formula-fed groups. There were differences in the values of some amino acids and blood biomarkers between the formula-fed groups, but the mean values for biomarkers were within the normal reference range. There were no differences in the occurrence of serious adverse events, general health, and incidence of dermatitis or medically diagnosed food allergy. The incidence of parentally reported blood-stained stools was higher in the goat milk formula-fed group, although this was a secondary outcome and its importance is unclear. Goat milk formula provided growth and nutritional outcomes in infants that did not differ from those provided by a standard whey-based cow milk formula.
The Relationship between Total Blood Cholesterol Levels and All-cause Mortality in Fukui City, and Meta-analysis of This Relationship in Japan

Shirasaki published a Japanese paper about the relationship between total cholesterol levels and all-cause mortality in Fukui City, Japan. His cholesterol data were not grouped according to ordinal 20mg⁄dL (0.52 mmol⁄L) intervals. In the present study, we re-calculated his data for meta-analysis. The relative risk (RR) of all-cause mortality adjusted for age and sex showed a decreasing trend with total cholesterol levels (p for trend <0.0001). In order to summarize the relationship between total cholesterol and all-cause mortality, literature describing this relationship in Japan was collected mainly using computer search engines. Literature published before 1995 was excluded. Reports with the total number of study subjects smaller than 5,000 were also excluded. Five reports were found suitable for meta-analysis of cholesterol levels and all-cause mortality. Meta-analysis revealed that the RR in the <160 mg⁄dL (<4.14 mmol⁄L) group [RR=1.71 (1.41, 2.08)] was significantly higher than in the reference group [160-199 mg⁄dL (4.14-5.17 mmol⁄L)], and that the RRs in the 200-239 mg⁄dL (5.18-6.21 mmol⁄L) group [RRs=0.83 (0.74, 0.94)] and ≥240 mg⁄dL (≥6.22 mmol⁄L) group [0.78 (0.65, 0.95)] were significantly lower than in the reference group when both men and women were combined. We suggest that Japanese subjects with cholesterol levels ≥240 mg⁄dL (≥6.22 mmol⁄L) should not be regarded as hypercholesterolemic or dyslipidemic except when having some genetic disorders like familial hypercholesterolemia because they are in the safest ranges in terms of all-cause mortality.
Convergence in relationships between leaf traits, spectra and age across diverse canopy environments and two contrasting tropical forests.

Leaf age structures the phenology and development of plants, as well as the evolution of leaf traits over life histories. However, a general method for efficiently estimating leaf age across forests and canopy environments is lacking. Here, we explored the potential for a statistical model, previously developed for Peruvian sunlit leaves, to consistently predict leaf ages from leaf reflectance spectra across two contrasting forests in Peru and Brazil and across diverse canopy environments. The model performed well for independent Brazilian sunlit and shade canopy leaves (R2 = 0.75-0.78), suggesting that canopy leaves (and their associated spectra) follow constrained developmental trajectories even in contrasting forests. The model did not perform as well for mid-canopy and understory leaves (R2 = 0.27-0.29), because leaves in different environments have distinct traits and trait developmental trajectories. When we accounted for distinct environment-trait linkages - either by explicitly including traits and environments in the model, or, even better, by re-parameterizing the spectra-only model to implicitly capture distinct trait-trajectories in different environments - we achieved a more general model that well-predicted leaf age across forests and environments (R2 = 0.79). Fundamental rules, linked to leaf environments, constrain the development of leaf traits and allow for general prediction of leaf age from spectra across species, sites and canopy environments.
Riboflavin (vitamin B2) and oxidative stress: a review

Oxidative stress is involved in the development of many chronic diseases. One of the main factors involved in oxidative stress reduction is increased antioxidant potential. Some nutrients such as vitamin C, vitamin E and carotenoids are known to act as antioxidants; however, riboflavin is one of the neglected antioxidant nutrients that may have an antioxidant action independently or as a component of the glutathione redox cycle. Herein, studies that have examined the antioxidant properties of riboflavin and its effect on oxidative stress reduction are reviewed. The results of the reviewed studies confirm the antioxidant nature of riboflavin and indicate that this vitamin can protect the body against oxidative stress, especially lipid peroxidation and reperfusion oxidative injury. The mechanisms by which riboflavin protects the body against oxidative stress may be attributed to the glutathione redox cycle and also to other possible mechanisms such as the conversion of reduced riboflavin to the oxidised form.
The cbfs triple mutants reveal the essential functions of CBFs in cold acclimation and allow the definition of CBF regulons in Arabidopsis.

In Arabidopsis, the C-repeat binding factors (CBFs) have been extensively studied as key transcription factors in the cold stress response. However, their exact functions in the cold response remains unclear due to the lack of a null cbf triple mutant. In this study, we used CRISPR/Cas9 technology to mutate CBF1 or CBF1/CBF2 in a cbf3 T-DNA insertion mutant to generate cbf1,3 double and cbf1 cbf2 cbf3 (cbfs) triple mutants. The response of the cbfs triple mutants to chilling stress is impaired. Furthermore, no significant difference in freezing tolerance was observed between the wild-type and the cbf1,3 and cbfs mutants without cold acclimation. However, the cbfs mutants were extremely sensitive to freezing stress after cold acclimation, and freezing sensitivity ranking was cbfs > cbf1,3 > cbf3. RNA-Seq analysis showed that 134 genes were CBF regulated, of which 112 were regulated positively and 22 negatively by CBFs. Our study reveals the essential functions of CBFs in chilling stress response and cold acclimation, as well as defines a set of genes as CBF regulon. It also provides materials for the genetic dissection of components in CBF-dependent cold signaling.
Organ failure and infection of pancreatic necrosis as determinants of mortality in patients with acute pancreatitis.

BACKGROUND & AIMS There is no consistency between the individual studies in the literature on whether organ failure (OF) or infected pancreatic necrosis (IPN) is the main determinant of severity in acute pancreatitis. We aimed to statistically aggregate the available data and determine the pooled influence of OF and IPN on mortality in patients with acute pancreatitis. METHODS The search for relevant observational studies was undertaken in the MEDLINE, EMBASE, and Scopus electronic databases, as well as in the proceedings of major gastroenterology meetings. The summary estimates are presented as relative risk (RR) and 95% confidence interval (CI). RESULTS Fourteen studies comprising 1478 patients with acute pancreatitis were meta-analyzed. A total of 600 patients developed OF and 179 of them died (mortality, 30%); 314 patients developed IPN and 102 of them died (mortality, 32%). In a stratified analysis, patients with OF and IPN had a significantly higher risk of death in comparison with patients with OF and no IPN (RR = 1.94; 95% CI: 1.32-2.85; P = .0007) and in comparison with patients with IPN and no OF (RR = 2.65; 95% CI: 1.30-5.40; P = .0007). CONCLUSIONS In patients with acute pancreatitis, the absolute influence of OF and IPN on mortality is comparable and thus the presence of either indicates severe disease. The relative risk of mortality doubles when OF and IPN are both present and indicates extremely severe disease or critical acute pancreatitis.
Patients with irritable bowel syndrome have altered emotional modulation of neural responses to visceral stimuli.

BACKGROUND & AIMS In patients with irritable bowel syndrome (IBS), pain amplification and hypervigilance might result from altered affective-motivational modulation of the pain response. We investigated the effects of emotional context on the behavioral and neural response to visceral stimuli in IBS patients. METHODS We used functional magnetic resonance imaging (fMRI) to assess the blood oxygen level-dependent response to nonpainful and painful rectal distensions in 15 female IBS patients and 12 healthy women. Distensions were delivered during psychologic stress or relaxation; data were compared with those in a neutral condition (control). Group and context-dependent differences in the processing of visceral stimulation were assessed at behavioral and the neuronal levels. Secondary analyses of group differences were performed using anxiety scores as a covariate because of higher anxiety symptoms among patients with IBS. RESULTS During rectal stimulation, IBS patients demonstrated more pronounced stress-induced modulation of neural activation in multiple brain regions, including the insula, midcingulate cortex, and ventrolateral prefrontal cortex. In response to relaxation, IBS patients demonstrated reduced modulation of distension-induced activation in the insula. During relaxation, the difference observed between groups could be accounted for by higher anxiety symptoms in patients with IBS; differential effects of stress in the insula and prefrontal regions were not attributable to anxiety. CONCLUSIONS IBS patients appear to have disrupted emotional modulation of neural responses to visceral stimuli, possibly reflecting the neural basis for altered visceral interoception by stress and negative emotions.
A chronobiological approach to addiction

Recent chronobiological studies show that drug consumption has a negative effect on circadian rhythmic expression. Circadian rhythm may even disappear in extreme cases, which suggests a lesser quality of the wake and sleep periods. Moreover, some circadian genes (Clock, Period) may be involved as biological risk factors in drug addictions. At the same time, the modification of their genetic expression has been found in patients with addiction disorders. Evening circadian typology is currently being considered as a risk factor in the onset and maintenance of drug consumption, while the morning typology appears to be a protection factor. The circadian genes are also related to psychopathologies such as mood disorders, and in the future, their implication in dual pathology should be further studied. Preventive and therapeutic approaches to addiction should take into account circadian rhythmic organization. In many cases, it may suffice to establish regular time patterns of wake–sleep, meals and daily activity with a tendency towards a morningness pattern of functioning. Other strategies, such as light therapy and melatonin administration, may be applied for long periods of time, since they have shown an excellent degree of security, and may also be a protective measure against relapse or the appearance of neuropsychiatric symptoms. Part of this work was presented at the 13th International Symposium on Substance Abuse Treatment (23–25 March, Barcelona, Spain).
MicroRNAs control intestinal epithelial differentiation, architecture, and barrier function.

BACKGROUND & AIMS Whereas the importance of microRNA (miRNA) for the development of several tissues is well established, its role in the intestine is unknown. We aimed to quantify the complete miRNA expression profile of the mammalian intestinal mucosa and to determine the contribution of miRNAs to intestinal homeostasis using genetic means. METHODS We determined the miRNA transcriptome of the mouse intestinal mucosa using ultrahigh throughput sequencing. Using high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP), we identified miRNA-messenger RNA target relationships in the jejunum. We employed gene ablation of the obligatory miRNA-processing enzyme Dicer1 to derive mice deficient for all miRNAs in intestinal epithelia. RESULTS miRNA abundance varies dramatically in the intestinal mucosa, from 1 read per million to 250,000. Of the 453 miRNA families identified, mmu-miR-192 is the most highly expressed in both the small and large intestinal mucosa, and there is a 53% overlap in the top 15 expressed miRNAs between the 2 tissues. The intestinal epithelium of Dicer1(loxP/loxP);Villin-Cre mutant mice is disorganized, with a decrease in goblet cells, a dramatic increase in apoptosis in crypts of both jejunum and colon, and accelerated jejunal cell migration. Furthermore, intestinal barrier function is impaired in Dicer1-deficient mice, resulting in intestinal inflammation with lymphocyte and neutrophil infiltration. Our list of miRNA-messenger RNA targeting relationships in the small intestinal mucosa provides insight into the molecular mechanisms behind the phenotype of Dicer1 mutant mice. CONCLUSIONS We have identified all intestinal miRNAs and shown using gene ablation of Dicer1 that miRNAs play a vital role in the differentiation and function of the intestinal epithelium.
III. Meta-Analysis of Risedronate for the Treatment of Postmenopausal Osteoporosis

Objective: To review the effect of risedronate on bone density and fractures in postmenopausal women. Data Sources: We searched MEDLINE from 1966 to the end of 2000 and examined citations of relevant articles and the proceedings of international osteoporosis meetings. Study Selection: We included eight randomized, placebo-controlled trials of postmenopausal women receiving risedronate or placebo with a follow-up of at least one year and providing data on bone density or fracture rate. Data Extraction: For each trial, two independent reviewers assessed the methodological quality and abstracted data. Data Synthesis: The major methodological limitation of the trials was the loss to follow-up, which was over 20% in most trials and over 35% in the largest study. However, the magnitude of the treatment effect was unrelated to loss to follow-up, and in one of the largest trials, more high-risk patients were lost to follow-up in the control than in the treatment group. The pooled relative risk (RR) for vertebral fractures in women given 2.5 mg or more of risedronate was 0.64 [95% confidence interval (CI) 0.54, 0.77]. The pooled RR of nonvertebral fractures in patients given 2.5 mg or more of risedronate was 0.73 (95% CI 0.61, 0.87). Risedronate produced positive effects on the percentage change in bone density of the lumbar spine, combined forearm, and femoral neck that were generally larger with the 5-mg daily dose than with cyclical administration or the 2.5-mg dose. The pooled estimate of the difference in percentage change between 5 mg risedronate and placebo after the final year of treatment (1.5-3 yr) was 4.54% (95% CI 4.12, 4.97) for the lumbar spine, and 2.75% (95% CI 2.32, 3.17) at the femoral neck. Conclusions: Risedronate substantially reduces the risk of both vertebral and nonvertebral fractures. This fracture reduction is accompanied by an increase in bone density of the lumbar spine and femoral neck in both early postmenopausal women and those with established osteoporosis.
Microsatellite alterations at selected tetranucleotide repeats are associated with morphologies of colorectal neoplasias.

BACKGROUND & AIMS Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) occurs during microsatellite instability (MSI) that is not associated with major defects in DNA mismatch repair (MMR) but rather the reduced (heterogenous) expression of the MMR protein hMSH3; it occurs in sporadic colorectal tumors. We examined the timing of development of EMAST during progression of colorectal neoplasias and looked for correlations between EMAST and clinical and pathology features of tumors. METHODS We evaluated tumor samples from a cohort of patients that had 24 adenomas and 84 colorectal cancers. EMAST were analyzed after DNA microdissection of matched normal and tumor samples using the polymorphic tetranucleotide microsatellite markers MYCL1, D9S242, D20S85, D8S321, and D20S82; data were compared with clinical and pathology findings. Traditional MSI analysis was performed and hMSH3 expression was measured. RESULTS Moderately differentiated adenocarcinomas and poorly differentiated adenocarcinomas had higher frequencies of EMAST (56.9% and 40.0%, respectively) than well-differentiated adenocarcinomas (12.5%) or adenomas (33.3%) (P = .040). In endoscopic analysis, ulcerated tumors had a higher frequency of EMAST (52.3%) than flat (44.0%) or protruded tumors (20.0%) (P = .049). In quantification, all tumors with >3 tetranucleotide defects lost MSH3 (>75% of cells); nuclear heterogeneity of hMSH3 occurred more frequently in EMAST-positive (40.0%) than in EMAST-negative tumors (13.2%) (P = .010). CONCLUSIONS EMAST is acquired during progression of adenoma and well-differentiated carcinomas to moderately and poorly differentiated carcinomas; it correlates with nuclear heterogeneity for hMSH3. Loss of hMSH3 corresponds with multiple tetranucleotide frameshifts. The association between EMAST and ulcerated tumors might result from increased inflammation.
Changes in turnover rather than production regulate biomass of ectomycorrhizal fungal mycelium across a Pinus sylvestris chronosequence.

In boreal forest soils, ectomycorrhizal fungi are fundamentally important for carbon (C) dynamics and nutrient cycling. Although their extraradical mycelium (ERM) is pivotal for processes such as soil organic matter build-up and nitrogen cycling, very little is known about its dynamics and regulation. In this study, we quantified ERM production and turnover, and examined how these two processes together regulated standing ERM biomass in seven sites forming a chronosequence of 12- to 100-yr-old managed Pinus sylvestris forests. This was done by determining ERM biomass, using ergosterol as a proxy, in sequentially harvested in-growth mesh bags and by applying mathematical models. Although ERM production declined with increasing forest age from 1.2 to 0.5 kg ha-1 d-1 , the standing biomass increased from 50 to 112 kg ha-1 . This was explained by a drastic decline in mycelial turnover from seven times to one time per year with increasing forest age, corresponding to mean residence times from 25 d up to 1 yr. Our results demonstrate that ERM turnover is the main factor regulating biomass across differently aged forest stands. Explicit inclusion of ERM parameters in forest ecosystem C models may significantly improve their capacity to predict responses of mycorrhiza-mediated processes to management and environmental changes.
A large spectrum of alpha and beta papillomaviruses are detected in human stool samples.

Human papillomaviruses (HPVs) have been detected in urban wastewaters, demonstrating that epitheliotropic viruses can find their way into sewage through the washing of skin and mucous membranes. Papillomavirus shedding through faeces is still an unexplored issue. The objective of the present study was to investigate the presence of HPVs in stool samples. We analysed 103 faecal specimens collected from hospitalized patients with diarrhoea using validated primers able to detect α, β and γ HPVs. PCR products underwent sequencing analysis and sequences were aligned to reference genomes from the Papillomavirus Episteme database. A total of 15 sequences were characterized from the faecal samples. Thirteen samples (12.6 %) were positive for nine genotypes belonging to the α and β genera: HPV32 (LR, α1), HPV39 (HR, α7), HPV44 (LR, α10), HPV8 (β1), HPV9, HPV23, HPV37, HPV38 and HPV120 (β2). Two putative novel genotypes of the β genus, species 1 and 2, were also detected. The tissue(s) of origin is unknown, since faeces can collect HPVs originating from or passing through the entire digestive system. To our knowledge, this is the first investigation on the occurrence and diversity of HPVs in faecal samples. Results from this study demonstrate that HPVs can find their way into sewage as a consequence of shedding in the faeces. This highlights the need for further studies aimed at understanding the prevalence of HPV in different water environments and the potential for waterborne transmission.
Oral administration of veratric acid, a constituent of vegetables and fruits, prevents cardiovascular remodelling in hypertensive rats: a functional evaluation

Abstract In our previous studies, veratric acid (VA) shows beneficial effect on hypertension and its associated dyslipidaemia. In continuation, this study was designed to investigate the effect of VA, one of the major benzoic acid derivatives from vegetables and fruits, on cardiovascular remodelling in hypertensive rats, primarily assessed by functional studies using Langendorff isolated heart system and organ bath system. Hypertension was induced in male albino Wistar rats by oral administration of N ω -nitro-l-arginine methyl ester hydrochloride (l-NAME) (40 mg/kg body weight (b.w.)) in drinking water for 4 weeks. VA was orally administered at a dose of 40 mg/kg b.w. l-NAME-treated rats showed impaired cardiac ventricular and vascular function, evaluated by Langendorff isolated heart system and organ bath studies, respectively; a significant increase in the lipid peroxidation products such as thiobarbituric acid-reactive substances and lipid hydroperoxides in aorta; and a significant decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase and levels of GSH, vitamin C and vitamin E in aorta. Fibrotic remodelling of the aorta and heart were assessed by Masson’s Trichrome staining and Van Gieson’s staining, respectively. In addition, l-NAME rats showed increased heart fibronectin expression assessed by immunohistochemical analysis. VA supplementation throughout the experimental period significantly normalised cardiovascular function, oxidative stress, antioxidant status and fibrotic remodelling of tissues. These results of the present study conclude that VA acts as a protective agent against hypertension-associated cardiovascular remodelling.