Miracle-dz/UniFAR-FTUs huggingface dataset:
Global Cancer in Women: Cancer Control Priorities

This review is an abbreviated version of a report prepared for the American Cancer Society Global Health department and EMD Serono, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany, which was released at the Union for International Cancer Control World Cancer Congress in Paris in November 2016. The original report can be found at https://www.cancer. org/health-care-professionals/our-global-health-work/global-cancer-burden/global-burden-of-cancer-in-women.html. Staff in the Intramural Research Department of the American Cancer Society designed and conducted the study, including analysis, interpretation, and presentation of the review. The funding sources had no involvement in the study design, data analysis and interpretation, or preparation of the review. The global burden of cancer in women has recently received much attention, but there are few comprehensive reviews of the burden and policy approaches to reduce it. This article, second in series of two, summarizes the most important cancer control priorities with specific examples of proven interventions, with a particular focus on primary prevention in low- and middle-income countries (LMIC). There are a number of effective cancer control measures available to countries of all resource levels. Many of these measures are extremely cost-effective, especially in the case of tobacco control and vaccination. Countries must prioritize efforts to reduce known cancer risk factors and make prevention accessible to all. Effective treatments and palliative care are also needed for those who develop cancer. Given scarce resources, this may seem infeasible in many LMICs, but past experience with other diseases like HIV, tuberculosis, and malaria have shown that it is possible to make affordable care accessible to all. Expansion of population-based cancer registries and research in LMICs are needed for setting cancer control priorities and for determining the most effective interventions. For LMICs, all of these activities require support and commitment from the global community. Cancer Epidemiol Biomarkers Prev; 26(4); 458–70. ©2017 AACR. See related article by Torre et al. in this CEBP Focus section, “Global Cancer in Women. ”
Species selection under long-term experimental warming and drought explained by climatic distributions.

Global warming and reduced precipitation may trigger large-scale species losses and vegetation shifts in ecosystems around the world. However, currently lacking are practical ways to quantify the sensitivity of species and community composition to these often-confounded climatic forces. Here we conducted long-term (16 yr) nocturnal-warming (+0.6°C) and reduced precipitation (-20% soil moisture) experiments in a Mediterranean shrubland. Climatic niche groups (CNGs) - species ranked or classified by similar temperature or precipitation distributions - informatively described community responses under experimental manipulations. Under warming, CNGs revealed that only those species distributed in cooler regions decreased. Correspondingly, under reduced precipitation, a U-shaped treatment effect observed in the total community was the result of an abrupt decrease in wet-distributed species, followed by a delayed increase in dry-distributed species. Notably, while partially correlated, CNG explanations of community response were stronger for their respective climate parameter, suggesting some species possess specific adaptations to either warming or drought that may lead to independent selection to the two climatic variables. Our findings indicate that when climatic distributions are combined with experiments, the resulting incorporation of local plant evolutionary strategies and their changing dynamics over time leads to predictable and informative shifts in community structure under independent climate change scenarios.
Understanding the origin of number sense: a review of fish studies

The ability to use quantitative information is thought to be adaptive in a wide range of ecological contexts. For nearly a century, the numerical abilities of mammals and birds have been extensively studied using a variety of approaches. However, in the last two decades, there has been increasing interest in investigating the numerical abilities of teleosts (i.e. a large group of ray-finned fish), mainly due to the practical advantages of using fish species as models in laboratory research. Here, we review the current state of the art in this field. In the first part, we highlight some potential ecological functions of numerical abilities in fish and summarize the existing literature that demonstrates numerical abilities in different fish species. In many cases, surprising similarities have been reported among the numerical performance of mammals, birds and fish, raising the question as to whether vertebrates' numerical systems have been inherited from a common ancestor. In the second part, we will focus on what we still need to investigate, specifically the research fields in which the use of fish would be particularly beneficial, such as the genetic bases of numerical abilities, the development of these abilities and the evolutionary foundation of vertebrate number sense. This article is part of a discussion meeting issue ‘The origins of numerical abilities’.
Reynolds number influence on the formation of vortical structures on a pitching flat plate

The impact of chord-based Reynolds number on the formation of leading-edge vortices (LEVs) on unsteady pitching flat plates is investigated. The influence of secondary flow structures on the shear layer feeding the LEV and the subsequent topological change at the leading edge as the result of viscous processes are demonstrated. Time-resolved velocity fields are measured using particle image velocimetry simultaneously in two fields of view to correlate local and global flow phenomena in order to identify unsteady boundary-layer separation and the subsequent flow structures. Finally, the Reynolds number is identified as a parameter that is responsible for the transition in mechanisms leading to LEV detachment from an aerofoil, as it determines the viscous response of the boundary layer in the vortex–wall interaction.
The connections between group maturity, software development velocity, and planning effectiveness

Empirical evidence regarding the connection between group development (maturity) and the success of software development teams is lacking. The purpose of this research is to gain a qualitative and quantitative understanding of how velocity and planning effectiveness of software teams connect to a group development model. The Group Development Questionnaire was given to 19 software developers from 4 work groups to assess their group development maturity. The work groups' responses to the survey were checked for correlation with development velocity and planning effectiveness. Semistructured interviews were conducted with 16 individuals from the same 4 work groups to explore issues about their group maturity and to validate the responses of the interviewees in the Group Development Questionnaire. The measurement of the fourth stage of group development had a strong association with the planning effectiveness measurement, which means that a team with less issues in the fourth phase of group development is more effective in adhering to its plans. On the other hand, group development and velocity showed no significant convergent validity. We conclude that the dynamics within software development teams might correlate to their ability to deliver the expected outcome as planned but not to their ability to develop tasks faster.
Applying transmission-coverage algorithms for secure geocasting in VANETs

Existing geocasting algorithms for VANETs provide either high availability or security, but fail to achieve both together. Most of the privacy preserving algorithms for VANETs have low availability and involve high communication and computation overheads. The reliable protocols do not guarantee secrecy and privacy. We propose a secure, privacy-preserving geocasting algorithm for VANETs, which uses direction-based dissemination. Privacy and security are achieved using public key encryption and authentication and pseudonyms. To reduce communication overheads resulting from duplication of messages, we adapt a transmission-coverage algorithm used in mobile sensor networks, where nodes delay forwarding messages based on its uncovered transmission perimeter after neighbouring nodes have broadcast the message. Our analysis shows that our protocol achieves a high delivery rate, with reasonable computation and communication overheads.
A porcine model of skin wound infected with a polybacterial biofilm

Abstract A clinically relevant porcine model of a biofilm-infected wound was established in 10 minipigs. The wounds of six experimental animals were infected with a modified polymicrobial Lubbock chronic wound biofilm consisting of Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Bacillus subtilis. Four animals served as uninfected controls. The wounds were monitored until they had healed for 24 days. The biofilm persisted in the wounds up to day 14 and significantly affected healing. The control to infected healed wound area ratios were: 45%/21%, 66%/37%, and 90%/57% on days 7, 10 and 14, respectively. The implanted biofilm prolonged inflammation, increased necrosis, delayed granulation and impaired development of the extracellular matrix as seen in histological and gene expression analyses. This model provides a therapeutic one-week window for testing of anti-biofilm treatments and for research on the pathogenesis of wound infections in pig that is clinically the most relevant animal wound healing model.
Regulatory role of the respiratory supercomplex factors in Saccharomyces cerevisiae

Significance The last steps of energy conversion in aerobic eukaryotes take place in cellular organelles called mitochondria. The process involves a number of protein complexes, referred to as the respiratory chain, that reside in the inner mitochondrial membrane. This chain shuttles electrons, which originate from degradation of foodstuff, to the acceptor dioxygen. The process is regulated to optimize the energy supply, depending on requirements and external factors. We found that two small proteins that have been found to associate with the respiratory–enzyme complexes regulate the electron flux at the last two components of the chain. Furthermore, we identified the regulatory mechanism at the molecular level. The respiratory supercomplex factors (Rcf) 1 and 2 mediate supramolecular interactions between mitochondrial complexes III (ubiquinol-cytochrome c reductase; cyt. bc1) and IV (cytochrome c oxidase; CytcO). In addition, removal of these polypeptides results in decreased activity of CytcO, but not of cyt. bc1. In the present study, we have investigated the kinetics of ligand binding, the single-turnover reaction of CytcO with O2, and the linked cyt. bc1-CytcO quinol oxidation-oxygen-reduction activities in mitochondria in which Rcf1 or Rcf2 were removed genetically (strains rcf1Δ and rcf2Δ, respectively). The data show that in the rcf1Δ and rcf2Δ strains, in a significant fraction of the population, ligand binding occurs over a time scale that is ∼100-fold faster (τ ≅ 100 μs) than observed with the wild-type mitochondria (τ ≅ 10 ms), indicating structural changes. This effect is specific to removal of Rcf and not dissociation of the cyt. bc1–CytcO supercomplex. Furthermore, in the rcf1Δ and rcf2Δ strains, the single-turnover reaction of CytcO with O2 was incomplete. This observation indicates that the lower activity of CytcO is caused by a fraction of inactive CytcO rather than decreased CytcO activity of the entire population. Furthermore, the data suggest that the Rcf1 polypeptide mediates formation of an electron-transfer bridge from cyt. bc1 to CytcO via a tightly bound cyt. c. We discuss the significance of the proposed regulatory mechanism of Rcf1 and Rcf2 in the context of supramolecular interactions between cyt. bc1 and CytcO.
The molecular genetics of the telomere biology disorders

ABSTRACT The importance of telomere function for human health is exemplified by a collection of Mendelian disorders referred to as the telomere biology disorders (TBDs), telomeropathies, or syndromes of telomere shortening. Collectively, the TBDs cover a spectrum of conditions from multisystem disease presenting in infancy to isolated disease presentations in adulthood, most notably idiopathic pulmonary fibrosis. Eleven genes have been found mutated in the TBDs to date, each of which is linked to some aspect of telomere maintenance. This review summarizes the molecular defects that result from mutations in these genes, highlighting recent advances, including the addition of PARN to the TBD gene family and the discovery of heterozygous mutations in RTEL1 as a cause of familial pulmonary fibrosis.
Indicadores predictivos de mortalidad y su relación con el tratamiento definitivo en la hemorragia subaracnoidea

Introduction: The subarachnoid hemorrhage (SAH) is a non solved health problem with a momentous significance influencing negatively in survival. The predictive or prognostic indicators of mortality have a significant role in clinical management of patients. Objectives: To assess entirely the patient presenting with SHA using predictive indicators characterizing the variables related to mortality. Method: A longitudinal, retrospective, cross-sectional, analytical and observational study was conducted in patients admitted in the care to severe patient area of the “Dr. Luis Diaz Soto” Central Military Hospital presenting with subarachnoid hemorrhage from January, 2000 to January, 2008 to determine the predictive indicators of mortality in relation to implementation of its definitive treatment. Results: The sample universe was of 58 patients, mortality was of 48.2 % in patients aged over 59 with predominance of female sex. Complications like the re-bleeding, intracerebral hemorrhage, vasospasm, respiratory infections and the pulmonary edema were the major causes of death. The predictive indicators of a high risk of death are the re-bleeding, intracerebral hemorrhage, the Fisher IV degrees and IV-V of the World Federation of Neurosurgeons (WFNS) and score < 8 of the Glasgow Coma Scale, the need of mechanical ventilation and the vasospasm. Conclusions: The mortality due to SHA is high and of multi-cause origin where the lack of a common management protocol could be determinant.
An Investigation of Classification Techniques For Handwritten Digit Recognition

The data for our project was taken from the MNIST dataset. As written on a Kaggle competition using the MNIST dataset, “The MNIST (’Modified National Institute of Standards and Technology’) dataset is a classic within the Machine Learning community that has been extensively studied. More detail about the dataset, including Machine Learning algorithms that have been tried on it and their levels of success, can be found at http://yann.lecun. com/exdb/mnist/index.html. ”
Peptide Blocking of PD-1/PD-L1 Interaction for Cancer Immunotherapy

A PD-L1–targeting peptide, TPP-1, was identified by bacterial surface display methods. TPP-1 was found to block PD-1/PD-L1 interactions, leading to T-cell reactivation, improved responses, and inhibition of tumor growth in a xenograft model. Immunotherapy has become a promising alternative therapeutic approach for cancer patients. Interruption of immune checkpoints, such as CTLA-4 and PD-1, has been verified to be a successful means for cancer therapy in clinical trials. mAb targeting PD-L1 has been approved to treat urothelial carcinoma, non–small cell lung cancer, or Merkel cell carcinoma by the FDA. However, the high cost of the antibody can limit its application. In our study, targeting PD-L1 peptide (TPP-1), which specifically binds to PD-L1 with high affinity, was identified through bacterial surface display methods. Using a T-cell activation assay and mixed lymphocyte reaction, TPP-1 was verified to interfere with the interaction of PD-1/PD-L1. To examine the inhibitory effect of TPP-1 on tumor growth in vivo, a xenograft mouse model using H460 cells was established. The growth rate of tumor masses in TPP-1 or PD-L1 antibody–treated mice was 56% or 71% lower than that in control peptide–treated mice, respectively, indicating that TPP-1 inhibits, or at least retards, tumor growth. IHC of the tumors showed that IFNγ and granzyme B expression increased in the TPP-1 or PD-L1 antibody–treated groups, indicating that TPP-1 attenuates the inhibitory effect of PD-L1 on T cells and that T cells may get reactivated. On the basis of our data, TPP-1 peptide could work as an alternative to antibodies for tumor immunotherapy. Cancer Immunol Res; 6(2); 178–88. ©2017 AACR.
Stimulation of luteinizing hormone release and cyclic nucleotide production by arachidonic acid in cultured pituitary gonadotrophs.

Gonadotropin-releasing hormone (GnRH) stimulates luteinizing hormone (LH) release and cyclic guanosine 3',5-cyclic monophosphate (cGMP) production in rat anterior pituitary cells through a calcium-dependent activation mechanism that involves increased phospholipid turnover and liberation of arachidonic acid. In enriched pituitary gonadotrophs, LH release was stimulated by arachidonic acid and its oxygenated metabolite, 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), in a dose-dependent manner. The prominent LH responses of purified gonadotrophs to arachidonic acid suggest that the secretory actions of arachidonate are exerted primarily on the gonadotroph and do not involve the participation of other pituitary cell types. Preincubation of pituitary cells with stimulatory concentrations of arachidonic acid for up to 120 min did not alter the subsequent LH responses elicited by GnRH, indicating that the secretory mechanism was unimpaired by arachidonate treatment and that no cross-desensitization occurs during sequential exposure of gonadotrophs to the two stimuli of LH release. Cyclic adenosine 3',5-monophosphate (cAMP) production was stimulated by 10 microM arachidonic acid to the same degree (about 2-fold) as by GnRH, but did not parallel the progressive LH response to higher arachidonate concentrations. cGMP production was initially stimulated by addition of arachidonic acid but returned to the control value after 5 min, whereas GnRH typically elicited a prolonged cGMP response. In contrast to the calcium-independent action of arachidonic acid, the stimulatory effect of 5-HETE on LH release required the presence of extracellular Ca2+, as previously observed for GnRH. These findings demonstrate that arachidonic acid and its metabolite, 5-HETE, partially reproduce the actions of GnRH upon LH release and cyclic nucleotide production. (ABSTRACT TRUNCATED AT 250 WORDS)
A Ba2+-Insensitive K+ Conductance in the Basolateral Membrane of Rabbit Cortical Thick Ascending Limb Cells

The nature of the K<sup>+</sup> exit across the basolateral membrane of microperfused rabbit cortical thick ascending limbs (cTALs) was investigated using the transepithelial and transmembrane potential difference (PD<sub>te</sub>, PD<sub>bl</sub>) and conductance measurements. An increase in bath K<sup>+</sup> concentration from 4 to 10, 25, 50 mmol/l depolarized the basolateral membrane in a concentration-dependent manner, accompanied by a decrease in the fractional resistance of the basolateral membrane (FR<sub>bl</sub>). The Cl<sup>–</sup> channel blocker, 5-nitro-2-(3-phenylpropyl-amino)-benzoic acid (NPPB), did not prevent these effects. The effect of Ba<sup>2+</sup> on PD<sub>bl</sub> was bimodally distributed: paradoxically, in the tubules in which Ba<sup>2+</sup> largely depolarized, the effects on PD<sub>bl</sub> of the bath K<sup>+</sup> concentration increases were not inhibited by extracellular Ba<sup>2+</sup>, in tubules in which Ba<sup>2+</sup> moderately depolarized, Ba<sup>2+</sup> partially inhibited the K<sup>+</sup> concentration increase-induced depolarization of the basolateral membrane. However, the parallel decrease in FR<sub>bl</sub> was Ba<sup>2+</sup> insensitive, indicating that the K<sup>+</sup> channel of the basolateral membrane was not modified by extracellular Ba<sup>2+</sup>. The Ba<sup>2+</sup>-induced depolarizations were prevented by furosemide suggesting that Ba<sup>2+</sup> acts by inhibiting basolateral KCl extrusion. Finally, the K<sup>+</sup> concentration increase-induced depolarizations were insensitive to tetraethylammonium, charybdotoxin, apamin and verapamil. In conclusion, the present study provides evidence that, in addition to a Ba<sup>2+</sup>-sensitive KCl cotransport system, the basolateral membrane of rabbit cTAL cells possesses a K<sup>+</sup> conductance which is insensitive to extracellular Ba<sup>2+</sup>.
Plasma midregional proadrenomedullin (MR-proADM) concentrations and their biological determinants in a reference population

Abstract Background: Midregional proadrenomedullin (MR-proADM) is emerging as a prognostic biomarker for detecting the failure of multiple organs. Establishment of scientifically robust reference intervals facilitates interpretation of laboratory test results. The objectives of this study were (i) to establish reliable reference intervals for plasma MR-proADM using a commercially available automated fluoroimmunoassay in apparently healthy individuals, and (ii) to identify biological determinants of MR-proADM concentrations. Methods: A total of 506 questionnaire-identified apparently healthy adults were enrolled in a single-center, cross-sectional study. A final reference group (n=172) was selected after exclusion of obese individuals, those with increased values of laboratory biomarkers indicating asymptomatic myocardial injury or dysfunction, ongoing inflammation, diabetes, dyslipidemia and renal dysfunction and outliers. Results: The 2.5th and 97.5th percentile intervals for MR-proADM values in the reference group (90% confidence interval) were 0.21 (0.19–0.23) and 0.57 (0.55–0.59) nmol/L, respectively. Although older age, higher values of HbA1c, C-reactive protein, B-type natriuretic peptide and body mass index, together with a history of smoking and a decreased estimated glomerular filtration rate were significantly associated with increasing concentrations of MR-proADM in both univariate and multivariate analyses, magnitudes of these relationships were modest and did not substantially influence MR-proADM reference intervals. Sex-dependent difference in MR-proADM reference intervals was not detected [0.19 (0.16–0.22)–0.56 (0.54–0.60) nmol/L in females vs. 0.22 (0.20–0.25)–0.58 (0.57–0.63) nmol/L in males]. Conclusions: Our study successfully established robust reference intervals for MR-proADM concentrations in plasma. Considering the negligible influence of potential biological determinants on plasma MR-proADM, we recommend the adoption of single reference intervals for adult population as a whole.