Miracle-dz/UniFAR-FTUs huggingface dataset:
Improving blood glucose level predictability using machine learning

This study was designed to improve blood glucose level predictability and future hypoglycemic and hyperglycemic event alerts through a novel patient‐specific supervised‐machine‐learning (SML) analysis of glucose level based on a continuous‐glucose‐monitoring system (CGM) that needs no human intervention, and minimises false‐positive alerts. The CGM data over 7 to 50 non‐consecutive days from 11 type‐1 diabetic patients aged 18 to 39 with a mean HbA1C of 7.5% ± 1.2% were analysed using four SML models. The algorithm was constructed to choose the best‐fit model for each patient. Several statistical parameters were calculated to aggregate the magnitudes of the prediction errors. The personalised solutions provided by the algorithm were effective in predicting glucose levels 30 minutes after the last measurement. The average root‐mean‐square‐error was 20.48 mg/dL and the average absolute‐mean‐error was 15.36 mg/dL when the best‐fit model was selected for each patient. Using the best‐fit‐model, the true‐positive‐hypoglycemia‐prediction‐rate was 64%, whereas the false‐positive‐ rate was 4.0%, and the false‐negative‐rate was 0.015%. Similar results were found even when only CGM samples below 70 were considered. The true‐positive‐hyperglycemia‐prediction‐rate was 61%. State‐of‐the‐art SML tools are effective in predicting the glucose level values of patients with type‐1diabetes and notifying these patients of future hypoglycemic and hyperglycemic events, thus improving glycemic control. The algorithm can be used to improve the calculation of the basal insulin rate and bolus insulin, and suitable for a closed loop “artificial pancreas” system. The algorithm provides a personalised medical solution that can successfully identify the best‐fit method for each patient.
A New Clamping Technique for Biomechanical Testing of Tendons in Small Animals

When biomechanical properties of tendons are studied, the technique of clamping the tendons in the testing machine presents a methodological challenge, especially when murine tendons are examined. These short tendons tend to rupture at the transition line to the fixation, leading to false interpretations. Therefore a new clamping technique for investigation of healthy murine Achilles tendons (n = 50) was developed, in which the intramuscular tendon fibers were fixed between two paper strips and the calcaneus was wedged into a conical slot in a wooden block and then mounted in the testing machine (n = 20). This technique was compared with the conventional clamping technique that fixes both ends of the tendon by clamps (n = 15) and an earlier described method that used glue or plastic cement for the fixation of the intramuscular tendon fibers and calcaneus in the testing machine (n
Intercellular Communication within the Rat Anterior Pituitary : Immunohistochemical Study on the Relationship between the Hypothalamus, Agranular Cells and GnRH Neurons in the Pars Tuberalis and Anterior Pituitary Gland

The pars tuberalis has been generally understood as a simple forward elongation of the glandular pituitary that develops into an architecturally similar structure. In rats, it is also believed that the pars tuberalis completely encircles the infundibular stalk at the ventral portion of hypothalamus. Intact Wistar-Imamichi rats were used in the present study, and frontal and sagittal serial sections of the pituitary gland/brain complex were prepared. Serial sections were stained with hematoxylin-eosin and with antibodies to LH-RH, S-100 protein or LH-RH receptor. Electron microscopic analyses were also conducted. The anatomical end of the epithelial structure of the pars tuberalis was observed at approximately 1 mm behind the optic chiasm. At this point, both the capillaries and the pars tuberalis spread and interdigitated over the median eminence. The pars tuberalis did not, however, completely encircle the pituitary stalk. Electron microscopic observations revealed some profiles of neuroendocrine nerve elements that were also present between the agranular cells of the pars tuberalis. A few LH-RH-positive nerve fibers were initially found just behind the optic chiasm, while the number of LH-RH-positive reactions increased around the capillary vessels. These reactions then decreased significantly and were sparsely distributed both in the diencephalon and in the area near the pituitary stalk where the two separated. LH-RH receptors were observed on S-100 protein-positive cells in the pars tuberalis. The present observations show the significance of the pars tuberalis and its relationship between the anterior pituitary gland and the hypothalamus as organs that possibly form another collaborating mechanism for the regulation of hormone secretion of the anterior pituitary gland.
Seasonal distribution of picoplanktonic cyanobacteria of Synechococcus type in the Eastern Skagerrak

Abstract Abundance of picoplanktonic chroococcoid cyanobacteria of Synechococcus type, inorganic nutrient levels and chl a were measured on 13 occasions from September 1989 to September 1990 in the eastern Skagerrak. Phycoerythrin-rich cyanobacteria (PEC) cells were present throughout the year but were most abundant in summer, when they also constituted the largest part of the phytoplank-ton biomass. Maximum abundance occurred in June when 2 x 108 cells 1-1 were recorded. PEC abundance was positively correlated with temperature and negatively correlated with nutrient concentrations. Our results support the general view that picophytoplankton are quantitatively most important under oligotrophic conditions and at high temperatures. PEC constituted a substantial part of the total phytoplankton biomass in the Skagerrak from May to September.
Interferon-γ Regulation of B Lymphocyte Differentiation: Activation of B Cells Is a Prerequisite for IFN-γ-Mediated Inhibition of B Cell Differentiation

Abstract The Th1 and NK cell-derived cytokine interferon-γ (IFN-γ) influences both immune and inflammatory responses, and under some circumstances, IFN-γ can inhibit B cell differentiation. We found that IFN-γ inhibited LPS-induced IgM production in B cells by reducing the precursor frequency of IgM-secreting cells. This occurred without a significant decrease in B cell proliferation in response to either LPS or F(ab′) 2 anti-IgM. We also found that IFN-γ inhibited IgM secretion, even when added as late as 48 hr after LPS stimulation. Small resting B cells were not affected by a pulse with IFN-γ. However, a pulse of IFN-γ inhibited the response of activated B cells to subsequent stimulation with LPS. Also, LPS upregulated expression of the IFN-γ receptor on B cells. Our studies show that IFN-γ targets stimulated but not resting B cells and suggest that IFN-γ plays an important role in the normal homeostatic control of B cell polyclonal responses.
Optimization of a chest computed tomography protocol for detecting pure ground glass opacity nodules: A feasibility study with a computer-assisted detection system and a lung cancer screening phantom

Objective This study aimed to optimize computed tomography (CT) parameters for detecting ground glass opacity nodules (GGNs) using a computer-assisted detection (CAD) system and a lung cancer screening phantom. Methods A lung cancer screening phantom containing 15 artificial GGNs (−630 Hounsfield unit [HU], 2–10 mm) in the left lung was examined with a CT scanner. Three tube voltages of 80, 100, and 120 kVp were used in combination with five tube currents of 25, 50, 100, 200, and 400 mA; additionally, three slice thicknesses of 0.625, 1.25, and 2.5 mm and four reconstruction algorithms of adaptive statistical iterative reconstruction (ASIR-V) of 30, 60, and 90% were used. For each protocol, accuracy of the CAD system was evaluated for nine target GGNs of 6, 8, or 10 mm in size. The cut-off size was set to 5 mm to minimize false positives. Results Among the 180 combinations of tube voltage, tube current, slice thickness, and reconstruction algorithms, combination of 80 kVp, 200 mA, and 1.25-mm slice thickness with an ASIR-V of 90% had the best performance in the detection of GGNs with six true positives and no false positives. Other combinations had fewer than five true positives. In particular, any combinations with a 0.625-mm slice thickness had 0 true positive and at least one false positive result. Conclusion Low-voltage chest CT with a thin slice thickness and a high iterative reconstruction algorithm improve the detection rate of GGNs with a CAD system in a phantom model, and may have potential in lung cancer screening.
CPK32-mediated phosphorylation is essential for the ammonium transport activity of AMT1;1 in Arabidopsis roots.

Protein kinase-mediated phosphorylation modulates the absorption of many nutrients in plants. CALCIUM-DEPENDENT PROTEIN KINASES (CPKs) are key players in plant signaling to translate calcium signals into diverse physiological responses. However, the regulatory role of CPKs in ammonium uptake remains largely unknown. Here, using methylammonium (MeA) toxicity screening, CPK32 was identified as a positive regulator of ammonium uptake in roots. CPK32 specifically interacted with the AMMONIUM TRANSPORTER 1;1 (AMT1;1) and phosphorylated AMT1;1 at the non-conserved serine residue S450 in the C-terminal domain. In functional analysis in Xenopus oocytes, co-expression CPK32 and AMT1;1 significantly enhanced the AMT1;1-mediated inward ammonium currents. In transgenic plants, the phosphomimic variant AMT1;1S450E, but not the nonphosphorylatable variant AMT1;1S450A, fully complemented the MeA insensitivity and restored high-affinity 15NH4+ uptake in both amt1;1 and cpk32 mutants. Moreover, in the CPK32 knockout background, AMT1;1 lost its ammonium transport activity entirely. These results indicate that CPK32 is a crucial positive regulator of ammonium uptake in roots and the ammonium transport activity of AMT1;1 is dependent on CPK32-mediated phosphorylation.
GENE EXPRESSION of LUTEINIZING HORMONE RECEPTOR (LHR) ISOFORMS IN GRANULOSA CELLS of FOLLICLES FROM NELLORE HEIFERS BEFORE, DURING, and AFTER FOLLICULAR DEVIATION

During bovine follicular development, there is a phase known as follicular deviation in which the future dominant follicle grows faster than the other follicles and acquires LH receptors (LHR). In Nellore breed, deviation occurs 2.5 days after ovulation, and at this time, the dominant follicle has in average a diameter of 6.0 mm. Some authors believe that LHRs are present in the future dominant follicle before deviation and are essential for this process. However, others are convinced that LHRs are present only during or after follicular deviation. The aim of the present experiment was to evaluate the expression of 4 LHR isoforms (M1 to M4) in granulosa cells of follicles from Nellore heifers before, during, and after follicular deviation. At a random stage of the estrous cycle (D0), Nellore heifers (n = 21) received a progesterone intravaginal device (1.0 g, Primer®, Tecnopec, Sao Paulo, Brazil) and 2.5 mg of estradiol benzoate (EB, i.m., Estrogin®, Farmavet, Sao Paulo, Brazil). Eight days later (D8) PGF2α was administered (150 μg d-cloprostenol, i.m., Prolise®, ARSA S.R.L., Buenos Aires, Argentina), and the device was removed. Twenty-four hours after device removal, cows were treated with EB (1.0 mg, i.m.), and from this point in time, the growth of the dominant follicle growth was observed by ultrasonography (US, Aloka 900, Tokyo, Japan) every 12 h. The animals were allocated in 3 groups: Group 2 (G2, 2 days after ovulation, n = 7), Group 2.5 (G2.5, 2.5 days after ovulation, n = 7), and Group 3 (G3, 3 days after ovulation, n = 7), and were slaughtered 2, 2.5, and 3 days after ovulation, respectively, in order to remove the ovaries. The granulosa cells, obtained from ovarian follicles, were separated for total RNA extraction, and the gene expression of LHR isoforms was measured by semiquantitative RT-PCR. Since LHR expression was not detected in Group 2 (follicles with 4.5 to 6.7 mm), comparisons were performed between groups G2.5 and G3 by ANOVA. The LHR expression was detected only in 2 samples of Group G2 (7.0-mm follicles) and was significantly higher in Group G3 (63.6%; follicles from 8 to 14 mm, P < 0.05). In all samples that expressed LHR, the 4 isoforms were present. It is concluded that LHR expression is present in granulosa cells of follicles from Nellore heifers after follicular deviation. Support and fellowship from FAPESP (Sao Paulo, Brazil). We are grateful to Tecnopec (Sao Paulo, Brazil) for providing intravaginal devices used in the experiment.
Less Animal-Based Food, Better Weight Status: Associations of the Restriction of Animal-Based Product Intake with Body-Mass-Index, Depressive Symptoms and Personality in the General Population

Restricting animal-based products from diet may exert beneficial effects on weight status; however, less is known about such a diet and emotional health. Moreover, personality traits, for example high neuroticism, may contribute to restrictive eating habits and potentially confound diet-health associations. We aim to systematically assess if restrictive dietary intake of animal-based products relates to lower weight and higher depressive symptoms, and if differences in personality traits play a significant role. Cross-sectional data from the baseline LIFE-Adult study were collected from 2011–2014 in Leipzig, Germany (n = 8943). Main outcomes of interest were dietary frequency of animal-derived products in the last year measured using a Food Frequency Questionnaire (FFQ), body-mass-index (BMI) (kg/m2), and the Center of Epidemiological Studies Depression Scale (CES-D). Personality traits were assessed in a subsample of n = 7906 using the Five Factor Inventory (NEO-FFI). Higher restriction of animal-based product intake was associated with a lower BMI, but not with depression scores. Personality, i.e., lower extraversion, was related to higher frequency of animal product intake. Moreover, personality traits were significantly associated with depressive symptoms, i.e., higher neuroticism, lower extraversion, lower agreeableness, lower conscientiousness, and with higher BMI. These findings encourage future longitudinal studies to test the efficacy of restricting animal-based products as a preventive and therapeutic strategy for overweight and obesity.
High temperature inactivation of cucumber and alfalfa mosaic viruses in Nicotiana rustica cultures

SUMMARY Cucumber mosaic (CMV) and alfalfa mosaic (AlfMV) viruses could not be detected in Nicotiana rustica tissues cultured at 32 °C for 16–18 days or at 40 °C for 5 days, but infectivity remained high in comparable tissue cultured at 22 °C. Incubation of infected cultures at 28–30 °C resulted in an initial reduction followed by a partial recovery in the infectivity of both viruses. The infectivity of CMV in tissues grown between 12 and 32 °C was highest in cultures grown at 12 °C. Although CMV infectivity was not detected in cultures after 16–18 days at 32 °C, virus was eliminated only after a further 30 days at 32 °C. When cultures were transferred from 32 to 22 °C after shorter treatment periods, infectivity rapidly increased to levels higher than those of infected tissues grown continuously at 22 °C. At 40 °C, CMV was eliminated from infected tissues after 9 days and AlfMV after 7 days. Cultures grown continuously at 40 °C deteriorated rapidly but, when grown under diurnal alternating periods of 8 h at 40 °C and 16 h at 22 °C, they remained viable and CMV was also inactivated.
The Species Richness-Energy Hypothesis in a System Where Historical Factors Are Thought to Prevail: Coral Reefs

Much of the variance in species richness of terrestrial organisms has been related to levels of available energy (the species richness-energy hypothesis). In contrast, the global patterns of coral diversity have been hypothesized to depend mainly on disturbance and historical factors. In this study, we test several general diversity hypotheses as they relate to hermatypic corals by examining the relationships between coral generic richness at 130 sites worldwide and descriptors of the environment that would be suggested by the hypotheses. The best environmental predictors of diversity are mean annual ocean temperature and an estimate of regional coral biomass, which suggests that available energy limits regional generic richness. In contrast, we found little evidence supporting other ecological hypotheses, including the hypotheses that disturbance or environmental stability is an important control of diversity. We also investigated historical hypotheses proposed to explain coral distributions. We found a relationship between coral richness and up-current island density that is consistent with vicariance models of speciation and theories of coral dispersal. Using multiple regression, 71% of the variation in coral generic richness could be statistically explained using a combination of variables representing both ecological and historical factors. Similar patterns exist for both coral species and reef fishes.
The NRF2/KEAP1 Axis in the Regulation of Tumor Metabolism: Mechanisms and Therapeutic Perspectives

The NRF2/KEAP1 pathway is a fundamental signaling cascade that controls multiple cytoprotective responses through the induction of a complex transcriptional program that ultimately renders cancer cells resistant to oxidative, metabolic and therapeutic stress. Interestingly, accumulating evidence in recent years has indicated that metabolic reprogramming is closely interrelated with the regulation of redox homeostasis, suggesting that the disruption of NRF2 signaling might represent a valid therapeutic strategy against a variety of solid and hematologic cancers. These aspects will be the focus of the present review.
Carbonic Anhydrase Sensitivity to Pesticides: Perspectives for Biomarker Development

Carbonic anhydrase (CA) is a widespread metalloenzyme playing a pivotal role in several physiological processes. Many studies have demonstrated the in vitro and in vivo sensitivity of CA to the exposure to several classes of pesticides in both humans and wildlife. This review aims to analyze and to discuss the literature available in this field, providing a comprehensive view useful to foresee perspectives for the development of novel CA-based pesticide biomarkers. The analysis of the available data highlighted the ability of several pesticide molecules to interact directly with the enzyme in humans and wildlife and to inhibit CA activity in vitro and in vivo, with possible alterations of key physiological functions. The analysis disclosed key areas of further research and, at the same time, identified some perspectives for the development of novel CA-based sensitive biomarkers to pesticide exposure, suitable to be used in several fields from human biomonitoring in occupational and environmental medicine to environmental monitoring on non-target species.
Enhanced Intestinal Absorption of Insulin by Capryol 90, a Novel Absorption Enhancer in Rats: Implications in Oral Insulin Delivery

Labrasol® is a self-emulsifying excipient that contains saturated polyglycolysed C6–C14 glycerides and this additive is known to improve the intestinal absorption of poorly absorbed drugs after oral administration. However, the effects of formulations similar to Labrasol® on the intestinal absorption of poorly absorbed drugs have not been characterized. In this study, we used insulin as a model peptide drug and examined the absorption-enhancing effects of Labrasol® and its related formulations for insulin absorption in rats. The co-administration of Labrasol-related formulations with insulin reduced the blood glucose levels. Among these formulations, Capryol 90 was the most effective additive. Notably, the effect of Capryol 90 was greater at pH 3.0 than at pH 7.0. Additionally, almost no mucosal damage was observed in the presence of these formulations, as these formulations did not affect the activity of lactate dehydrogenase (LDH) and the amount of protein released from the small intestine. In mechanistic studies, Capryol 90 improved the stability of insulin and suppressed the association with insulin under acidic conditions. The loosening of the tight junctions (TJs) could be the underlying mechanism by which Capryol 90 improved intestinal insulin absorption via a paracellular route. These findings suggest that Capryol 90 is an effective absorption enhancer for improving the intestinal absorption of insulin, without inducing serious damage to the intestinal epithelium.
Sepsis Associated Delirium

Sepsis is a potentially life-threatening condition caused by a systemic dysregulated host response to infection. The brain is particularly susceptible to the effects of sepsis with clinical manifestations ranging from mild confusion to a deep comatose state. Sepsis-associated delirium (SAD) is a cerebral manifestation commonly occurring in patients with sepsis and is thought to occur due to a combination of neuroinflammation and disturbances in cerebral perfusion, the blood brain barrier (BBB) and neurotransmission. The neurological impairment associated with SAD can persist for months or even longer, after the initial septic episode has subsided which may impair the rehabilitation potential of sepsis survivors. Early identification and treatment of the underlying sepsis is key in the management of SAD as once present it can be difficult to control. Through the regular use of validated screening tools for delirium, cases of SAD can be identified early; this allows potentially aggravating factors to be addressed promptly. The usefulness of biomarkers, neuroimaging and electroencephalopathy (EEG) in the diagnosis of SAD remains controversial. The Society of Critical Care Medicine (SCCM) guidelines advise against the use of medications to treat delirium unless distressing symptoms are present or it is hindering the patient’s ability to wean from organ support.
Cell kinetics: prognostic and therapeutic implications in human tumours

Clinical evidence has shown the limitation of pathological staging to give accurate prognostic information and its inability to predict clinical response to specific treatments. It therefore has been considered of utmost importance to integrate pathological stage with biological variables of consolidated predictive relevance to improve prognostic accuracy and possibly to identify indicators of response to different treatments. With regard to the first point, successive generations of prognostic factors have been proposed (Table 1): a first generation of pathological factors including tumour size, stage and morphology; a second generation including biochemical markers, steroid and growth factor receptors, cell kinetics and ploidy; and a third generation including oncogenes and oncosuppressor genes, proteases, extra-cellular matrix-related antigens and angiogenesis markers. For some tumour types, biological markers have been increasingly used to complement clinicopathological findings for a more accurate definition of individual patient prognosis and for helping clinicians in treatment decision making.
The evolutionary significance of genetic variation at enzyme synthesizing loci in the teleost Fundulus heteroclitus

Using the teleost Fundulus heteroclitus as an experimental model, we demonstrate how a multi-disciplinary approach to problems of intraspecies genetic variation can provide a better understanding of complex biodiversity problems than can be addressed by a more monolithic approach. We emphasize the importance of starting with simple molecular systems and making predictions that can be tested by experimentation at a higher level of biological complexity-leading from molecules to cells to organ systems to organisms and eventually laboratory and field selection experiments. Using this interdisciplinary approach, we address the classical ‘selectionisti neutralist’ controversy.