Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of heart rate variability in diabetic patients affected by autonomic cardiovascular neuropathy

In this paper, time- and frequency-domain parameters of the heart rate variability (HRV) are investigated in 45 Holter records for a group of diabetic patients with neuropathy (DNG) other group of diabetics without neuropathy (DWNG) and the control group (CG). Obtained results show that: 1) DNG vs. CG present significant differences of parameters in time- and frequency-domain at diurnal and nocturnal periods. 2) Only frequency-domain parameters can distinguish diabetic patients with and without neuropathy. 3) No differences have been appreciated between control and diabetic patients without neuropathy.
Comprehending Drug Use: Ethnographic Research at the Social Margins

Comprehending Drug Use , the first full-length critical overview of the use of ethnographic methods in drug research, synthesizes more than one hundred years of study on the human encounter with psychotropic drugs. J. Bryan Page and Merrill Singer create a comprehensive examination of the whole field of drug ethnography-methodology that involves access to the hidden world of drug users, the social spaces they frequent, and the larger structural forces that help construct their worlds. They explore the important intersections of drug ethnography with globalization, criminalization, public health (including the HIV/AIDS epidemic, hepatitis, and other diseases), and gender, and also provide a practical guide of the methods and career paths of ethnographers.
Differences in functional and xylem anatomical features allow Cistus species to co-occur and cope differently with drought in the Mediterranean region

A significant increase in drought events frequency is predicted for the next decades induced by climate change, potentially affecting plant species mortality rates and distributions worldwide. The main trigger of plant mortality is xylem hydraulic failure due to embolism and induced by the low pressures at which water is transported through xylem. As the Mediterranean basin will be severely affected by climate change, the aim of this study was to provide novel information about drought resistance and tolerance of one of its most widely distributed and common genera as a case study: the genus Cistus. Different functional and anatomical traits were evaluated in four co-occurring Cistus species in the Mediterranean Montado ecosystem. Soil water availability for each species was also assessed to evaluate if they show different ecological niches within the area. Results showed physiological and xylem anatomical differences between the four co-occurring species, as well as in the soil water availability of the sites they occupy. Despite the significant differences in embolism resistance across species, no trade-off between hydraulic safety and efficiency was observed. Interestingly, species with narrower vessels showed lower resistance to embolism than those with higher proportions of large conduits. No correlation, however, was observed between resistance to embolism and wood density. The four species showed different water-use and drought-tolerance strategies, occupying different ecological niches that would make them cope differently with drought. These results will allow us to improve the predictions about the expected changes in vegetation dynamics in this area due to ongoing climate change.
Proteomic Analysis of Tendon Extracellular Matrix Reveals Disease Stage-specific Fragmentation and Differential Cleavage of COMP (Cartilage Oligomeric Matrix Protein)*

Background: Tendon disease is characterized by extensive remodeling of the extracellular matrix. Results: Novel COMP cleavage fragments were identified in both an in vitro inflammatory model and natural disease. Conclusion: Inflammatory mediators drive distinct COMP fragmentation at different stages of tendon disease. Significance: Novel COMP neo-terminal fragments provide opportunities for developing markers for tendon injury. During inflammatory processes the extracellular matrix (ECM) is extensively remodeled, and many of the constituent components are released as proteolytically cleaved fragments. These degradative processes are better documented for inflammatory joint diseases than tendinopathy even though the pathogenesis has many similarities. The aims of this study were to investigate the proteomic composition of injured tendons during early and late disease stages to identify disease-specific cleavage patterns of the ECM protein cartilage oligomeric matrix protein (COMP). In addition to characterizing fragments released in naturally occurring disease, we hypothesized that stimulation of tendon explants with proinflammatory mediators in vitro would induce fragments of COMP analogous to natural disease. Therefore, normal tendon explants were stimulated with IL-1β and prostaglandin E2, and their effects on the release of COMP and its cleavage patterns were characterized. Analyses of injured tendons identified an altered proteomic composition of the ECM at all stages post injury, showing protein fragments that were specific to disease stage. IL-1β enhanced the proteolytic cleavage and release of COMP from tendon explants, whereas PGE2 had no catabolic effect. Of the cleavage fragments identified in early stage tendon disease, two fragments were generated by an IL-1-mediated mechanism. These fragments provide a platform for the development of neo-epitope assays specific to injury stage for tendon disease.
Proapoptotic Bax and Bak Proteins Form Stable Protein-permeable Pores of Tunable Size

Background: During apoptosis Bax/Bak release differently sized proteins out of the mitochondria. Results: The size of Bax/Bak pores depends on protein concentration. Conclusion: Bax/Bak form stable toroidal pores tunable in size. Significance: Pore size-tuning constitutes a new level for the regulation of Bax/Bak activity. The Bcl-2 proapoptotic proteins Bax and Bak mediate the permeabilization of the mitochondrial outer membrane during apoptosis. Current models consider that Bax and Bak form pores at the mitochondrial outer membrane that are responsible for the release of cytochrome c and other larger mitochondrial apoptotic factors (i.e. Smac/DIABLO, AIF, and endoglycosidase G). However, the properties and nature of Bax/Bak apoptotic pores remain enigmatic. Here, we performed a detailed analysis of the membrane permeabilizing activity of Bax and Bak at the single vesicle level. We directly visualized that cBid-activated Bax and BakΔC21 can form membrane pores large enough to release not only cytochrome c, but also allophycocyanine, a protein of 104 kDa. Interestingly, the size of Bax and BakΔC21 pores is not constant, as typically observed in purely proteinaceous channels, but evolves with time and depends on protein concentration. We found that Bax and BakΔC21 formed long-lived pores, whose areas changed with the amount of Bax/BakΔC21 but not with cardiolipin concentration. Altogether, our results demonstrate that Bax and BakΔC21 follow similar mechanisms of membrane permeabilization characterized by the formation of protein-permeable pores of dynamic size, in agreement with the proteolipidic nature of these apoptotic pores.
Application of the commission's recommendations for the protection of people in emergency exposure situations

Abstract Editorial Executive summary 1. Introduction 2. Scope of this advice 3. Objectives of protection in emergency exposure situations 4. Protection of emergency workers 5 Description of emergency exposure situations 6 Applying the Commission's System to emergency exposure situations 7. Arrangements for emergency exposure situations 8. Implementing protection strategies 9. Transition to rehabilitation References Annexes: A. Assessment of the contribution of different exposure pathways to the residual dose B. Characteristics of selected individual urgent protective measures C. Specific guidance for the termination of protective measures ADDITIONAL MATERIAL The history of ICRP and the evolution of its policies by Jack Valentin and Roger Clarke
Evolutionary trade-offs between drought resistance mechanisms across a precipitation gradient in a seasonally dry tropical oak (Quercus oleoides).

Tree Physiology 2017; doi:10.1093/treephys/tpx040 When this paper was first published on the Advance Access section of the Tree Physiology website, there were some errors in Figure 2J. ‘gs,mass’ on the y-axis and legend for Figure2J should have read ‘gs,area’. ‘mol H2O kg −1 s’ on the y-axis of Figure2J should have read ‘mol H2O m −2 s’. These errors have been corrected online and in print. The authors apologise for this error.
Asymmetrical Fc Engineering Greatly Enhances Antibody-dependent Cellular Cytotoxicity (ADCC) Effector Function and Stability of the Modified Antibodies*

Background: Co-crystal structure of Fc-FcγRIII complex revealed that Fc binds to FcγRIII asymmetrically. Results: We identified a panel of novel Fc heterodimers with enhanced ADCC activity. Conclusion: Asymmetrical Fc engineering is an efficient approach for enhancing ADCC activity and stability of engineered antibodies. Significance: The discovery could be applied in therapeutic antibodies for the treatment of cancers and infectious diseases. Antibody-dependent cellular cytotoxicity (ADCC) is mediated through the engagement of the Fc segment of antibodies with Fcγ receptors (FcγRs) on immune cells upon binding of tumor or viral antigen. The co-crystal structure of FcγRIII in complex with Fc revealed that Fc binds to FcγRIII asymmetrically with two Fc chains contacting separate regions of the FcγRIII by utilizing different residues. To fully explore this asymmetrical nature of the Fc-FcγR interaction, we screened more than 9,000 individual clones in Fc heterodimer format in which different mutations were introduced at the same position of two Fc chains using a high throughput competition AlphaLISA® assay. To this end, we have identified a panel of novel Fc variants with significant binding improvement to FcγRIIIA (both Phe-158 and Val-158 allotypes), increased ADCC activity in vitro, and strong tumor growth inhibition in mice xenograft human tumor models. Compared with previously identified Fc variants in conventional IgG format, Fc heterodimers with asymmetrical mutations can achieve similar or superior potency in ADCC-mediated tumor cell killing and demonstrate improved stability in the CH2 domain. Fc heterodimers also allow more selectivity toward activating FcγRIIA than inhibitory FcγRIIB. Afucosylation of Fc variants further increases the affinity of Fc to FcγRIIIA, leading to much higher ADCC activity. The discovery of these Fc variants will potentially open up new opportunities of building the next generation of therapeutic antibodies with enhanced ADCC effector function for the treatment of cancers and infectious diseases.
Seasonal importance of flowers to Costa Rican capuchins (Cebus capucinus imitator): Implications for plant and primate.

OBJECTIVES Our goal is to investigate flower foraging by capuchin monkeys, a behavior rarely studied in wild primates. We ask what drives seasonal variation in florivory rates: flower quality and abundance or fluctuations in fruit and invertebrate abundances. We explore how capuchins affect the reproductive success of flower food species by quantifying the potential pollination rate. MATERIALS AND METHODS We followed capuchin groups from dawn to dusk and recorded all flower foraging bouts. Flower food nutritional composition was compared to fruit and invertebrate foods. We recorded overall flower, fruit, and invertebrate abundances and compared the rate of flower foraging to these. We estimated the likelihood of pollination from the proportion of flower patch visits to each plant species that satisfied minimum behavioral requirements. RESULTS Flower eating was highly seasonal, and was significantly negatively related to overall fruit and invertebrate abundance but not flower abundance. Although smaller than most fruits, flowers were nutritionally comparable to fruit foods by dry mass and contained higher average concentrations of protein. Capuchins are likely pollinators for Luehea speciosa; most foraging visits to this species occurred in a manner that makes outcrossing or geitonogamous pollination likely. DISCUSSION Flowers are an important seasonal resource for capuchins. Flowers likely act as fallback foods during periods of reduced fruit and invertebrate abundance, and may exert evolutionary pressure disproportionate to their consumption. Capuchin florivory likely affects the reproductive success of some plants, potentially shaping forest structure. Our study illustrates the value of assessing the importance of rare foods in the primate diet.
Metabolome and transcriptome profiling reveal new insights into somatic embryo germination in Norway spruce (Picea abies)

Transcriptome, metabolome and histological profiling were performed on normal and aberrant somatic embryo germinants of Norway spruce (Picea abies L. Karst) providing a simplistic systems biology description of conifer germination. Aberrant germinants (AGs) formed periderm-like tissue at the apical pole and lacked shoot growth above the cotyledons. Transcriptome profiling (RNA-Sequencing) revealed a total of 370 differentially expressed genes at ≥1 or ≤-1 log2-fold change, where 92% were down-regulated in AGs compared with normal germinants (NGs). Genes associated with shoot apical meristem formation were down-regulated in AGs, or not differentially expressed between AGs and NGs. Genes involved in hormone signaling and transport were also down-regulated. Metabolite profiling by gas chromatography-mass spectrometry (MS) and liquid chromatography-MS revealed biochemical difference between AGs and NGs, notably increased levels of sugars including glucose in AGs. Genes involved in glucose signaling were down-regulated and genes involved in starch biosynthesis were up-regulated, suggesting involvement of sugar signaling during late embryo development and germination. The overall results provide new data enabling further studies to confirm potential markers for a normal germination process in conifers.
Efeito de fármacos ototóxicos na audição de recém-nascidos de alto risco

PURPOSE: To calculate the incidence of sensorineural hearing loss (SNHL), to verify if there is a causal association between the use of ototoxic drugs and SNHL, and to establish the frequency of genetic mutations related to SNHL in high risk newborns. METHODS: The study was a retrospective and prospective cohort research with 250 children. Data was gathered from subjects' charts and with their caregivers. Moreover, subjects were submitted to auditory evaluation with distortion product otoacoustic emissions, timpanometry, visual reinforcement audiometry, auditory brainstem response and transient otoacoustic emissions. The study of the genetic mutation 35delG, and the mitochondrial mutations A1555G and A7445G was essential to evaluate the possibility that SNHL had a non-syndromic genetic origin. The association between the medicine use and the occurrence of hearing loss had been analyzed. RESULTS: The incidence of SNHL in high risk newborns was 11.6%, and causal associations between SNHL and the drugs administered were: amikacin and cefotaxime (OR=5.35), cefotaxime and furosemide (OR=7.02), ceftazidime and vancomycin (OR=9.12). The frequencies of the mutation 35deIG and mitochondrial mutations A1555G and A7445G were, respectively, 0.8% and 0%. CONCLUSION: The incidence of SNHL in high risk newborns was high, showing an important causal relation with the use of ototoxic drugs and a small relation with genetic mutations.
Age estimation in older adults: Use of pulp/tooth ratios calculated from tooth sections.

OBJECTIVES Accurate age estimates are foundational for bioarchaeological research, yet the ability to accurately age older adult skeletons remains elusive. This study uses a new version of pulp/tooth area calculations to investigate chronological age of older archaeological individuals. MATERIALS AND METHODS Pulp/tooth area ratios were calculated on modern control teeth (n = 10) that were first radiographed and then sectioned for comparative analysis. Pulp/tooth area ratios were determined on sectioned teeth using ImageJ software for: (a) modern individuals of known age (n = 26); (b) individuals from Belleville, Ontario, Canada (1821-1874) with documented age (n = 50); and (c) Belleville individuals with skeletally estimated age (n = 122). RESULTS Calculations from tooth sections on modern teeth (n = 10) resulted in a mean absolute error (MAE) of ±3.9 years, whereas the radiographic method for the same teeth had an MAE of ±14.45 years. Results indicate that sectioned pulp/tooth area ratios are a significant predictor of chronological age (p < .005), with MAEs of ±4.53 years for Belleville and ±3.77 years for modern individuals. There were no statistically significant differences in age estimations between modern and archaeological individuals, or with respect to tooth type, sex, or intra/inter-observer estimations. DISCUSSION This study provides a new more accurate method for estimating age-at-death, particularly for individuals in the 50+ age category. Sectioning the teeth and directly measuring exposed pulp chambers results in age estimations that were within ±4.15 years for both modern and archaeological individuals, thus presenting a method that will enhance the ability to age older individuals.
Strand-specific Recognition of DNA Damages by XPD Provides Insights into Nucleotide Excision Repair Substrate Versatility*

Background: XPD is important for DNA lesion recognition by the nucleotide excision repair (NER) system. Results: Dependent on the lesion type, XPD recognizes lesions either on the protein-translocated or on the nontranslocated DNA strand. Conclusion: XPD employs different recognition strategies for different types of damage. Significance: Different lesion-specific recognition approaches may enhance the remarkably broad target spectrum of NER. Recognition and removal of DNA damages is essential for cellular and organismal viability. Nucleotide excision repair (NER) is the sole mechanism in humans for the repair of carcinogenic UV irradiation-induced photoproducts in the DNA, such as cyclobutane pyrimidine dimers. The broad substrate versatility of NER further includes, among others, various bulky DNA adducts. It has been proposed that the 5′-3′ helicase XPD (xeroderma pigmentosum group D) protein plays a decisive role in damage verification. However, despite recent advances such as the identification of a DNA-binding channel and central pore in the protein, through which the DNA is threaded, as well as a dedicated lesion recognition pocket near the pore, the exact process of target site recognition and verification in eukaryotic NER still remained elusive. Our single molecule analysis by atomic force microscopy reveals for the first time that XPD utilizes different recognition strategies to verify structurally diverse lesions. Bulky fluorescein damage is preferentially detected on the translocated strand, whereas the opposite strand preference is observed for a cyclobutane pyrimidine dimer lesion. Both states, however, lead to similar conformational changes in the resulting specific complexes, indicating a merge to a “final” verification state, which may then trigger the recruitment of further NER proteins.
Clinical and preclinical pharmacokinetic and dynamic studies with cisplatin, topotecan and docetaxel

Sample preparation for measurement of nonprotein bound platinum was evaluated by precipitation of plasma proteins with cold ethanol. The method was compared with the routinely used plasma ultrafiltration and with trichloroacetic acid (TCA) protein precipitation. After Incubation of human plasma samples with cisplatln or carboplatln unbound platinum concentrations were determined applying Amlcon Dlaflo ultrafiltration membranes and Mlilipore ultrafree·MC filters. For protein precipitation 1 ml of cold (-20 0 C) pure ethanol was added to 0.5 ml of human plasma and the supernatant was collected after 2 hours, or 0.5 ml of cold 20% TCA was added to 0.5 ml of plasma (22), Platinum was analyzed by atomic absorption spectrophotometry (AAS)' There were no significant differences between the ethanol and ultrafiltration methods in the unbound platinum concentration. The protein content In the supernatant (1.00 ± 0.20 %) was slightly higher than In the Amicon (0.58 ± 0.05 %) and Millipore (0.55 ± 0.04 %) ultrafiltrates. on average, the TCA and ethanol method seemed to be equally appropriate. The ethanol precipitation method is concluded to be simple, convenient, reproducible and has negligible costs. INTRODUCTION The quantltatlon of the unbound, I.e. nonprotein bound, plasma concentration of platinum is important for determination of the pharmacokinetics of the platinum drugs cisplatin and carboplatln. Only the unbound concentration of the drug Is likely to be pharmacologically active. After intravenous administration clsplatln and carboplatin become tightly bound to plasma proteins and other tissue components. previous studies have revealed that the binding to plasma proteins Is covalent and almost Irreversible (3, 4), Due to Its high reactivity the binding of cisplatin to plasma proteins Is very rapid, whereas the rate of binding of carboplatin is much lower (9, 10, 23, 241. Plasma ultrafiltration for the measurement of unbound platinum applying ultrafiltration tubes Is routinely used for this assay (2, 6, 7, 9,11,16,17,23), Mostly a cut off level of the filtration membranes of 30.000 D Is used. It has previously been suggested that precipitation of plasma proteins with cold ethanol may be a good alternative to the ultrafiltration of plasma for measurement of unbound platinum (181. In addition, trichloroacetic acid (TCAl has been used to measure unbound platinum (8, 13, 21, 22, 25). Here we report experiments In which the ethanol precipitation method is validated and compared with the results obtained with 2 ultrafiltration systems and the TCA precipitation method.
Reliability of the School Food Checklist for in-school audits and photograph analysis of children's packed lunches.

BACKGROUND Assessment of children's diets is problematic, typically relying on error-prone parent or child recall or reporting, or resource intensive direct observation. The School Food Checklist (SFC) is an objective instrument comprising of 20 food and beverage categories designed to measure the foods contained in children's packed lunches. The present study aimed to assess intra-rater and inter-rater reliability of each of the food and beverage categories of the SFC for both in-school audits and photograph analysis of children's school lunches. METHODS Participants comprised 176 children aged 5-8 years from five primary schools in Northern Metropolitan Melbourne. The SFC was used to measure the foods contained in children's packed lunches in the school setting and using photographs. Photograph analysis was conducted by the auditors 2-3 months after completion of in-school audits. RESULTS Both intra-rater [intra-class correlation coefficient (ICC) = 0.78-1] and inter-rater (ICC = 0.50-0.95) reliability analysis indicated strong agreement for in-school auditing. With the exception of the food category titled 'leftovers', there was strong intra-rater reliability for auditors' live audits and their analysis of photographs [ICC = 0.57-0.98 (Auditor 1); ICC = 0.72-0.90 (Auditor 2)], and strong inter-rater reliability for photograph analysis (ICC = 0.68-0.92). CONCLUSIONS The SFC is a reliable method of measuring the foods and beverages contained in children's packed lunches when used in the school setting or for photograph analysis. This finding has broad implications, particularly for the use of photograph analysis, because this approach offers a convenient and cost effective method of measuring what food and beverages children bring to school in home packed lunches.