Miracle-dz/UniFAR-FTUs huggingface dataset:
Multimodality therapy in early-stage neuroendocrine carcinoma of the uterine cervix.

OBJECTIVE Patients with early-stage neuroendocrine cervical carcinoma (NECC) have a high mortality rate despite aggressive therapy. The rarity of this tumor precludes initiation of a randomized, prospective trial. We reviewed our experience in early stage disease and performed a meta-analysis of the literature to identify prognostic factors and determine optimal multimodality therapy. METHODS Eleven women with International Federation of Gynecology and Obstetrics (FIGO) early stage (IB--IIA) NECC were treated with surgery and chemotherapy at our institutions between 1978 and 1998. Administration of radiation therapy was recorded, but not required for inclusion in this study. A gynecologic pathologist reviewed all histopathologic sections. Medical records were retrospectively reviewed and clinical data obtained. Twenty-three early-stage NECC patients who were similarly treated during the study interval were identified by a Medline search of the English literature and included in the analysis. The Kaplan--Meier method and log-rank test were used for survival analysis. RESULTS The overall 2-year survival rate for the 34 patients was 38%. The median age was 37 years (range, 20--75 years). Median cervical tumor diameter was 3.2 cm (range 0.5--11.0 cm). Lymphovascular space invasion was present in 21 (78%) of 27 patients (7 unknown). Fifteen (52%) of twenty-nine had lymph node metastases (5 unknown). Fifteen patients received postoperative platinum/etoposide (PE), seven received vincristine/adriamycin/cyclophosphamide (VAC), two received alternating cycles of VAC and PE, and ten received other chemotherapy regimens. Twenty women were treated with radiation therapy. The presence of lymph node metastases was a poor prognostic factor (P < 0.001). PE and VAC chemotherapy was associated with increased survival (P < 0.01). CONCLUSION NECC is a highly lethal variant of cervical cancer. The presence of lymph node metastases is the most important prognostic variable. Postoperative VAC or PE appears most likely to improve chances for survival.
Prediction of protein surface accessibility with information theory

A new, simple method based on information theory is introduced to predict the solvent accessibility of amino acid residues in various states defined by their different thresholds. Prediction is achieved by the application of information obtained from a single amino acid position or pair‐information for a window of seventeen amino acids around the desired residue. Results obtained by pairwise information values are better than results from single amino acids. This reinforces the effect of the local environment on the accessibility of amino acid residues. The prediction accuracy of this method in a jackknife test system for two and three states is better than 70 and 60%, respectively. A comparison of the results with those reported by others involving the same data set also testifies to a better prediction accuracy in our case. Proteins 2001;42:452–459. © 2001 Wiley‐Liss, Inc.
Subjective Duration Distortions Mirror Neural Repetition Suppression

Background Subjective duration is strongly influenced by repetition and novelty, such that an oddball stimulus in a stream of repeated stimuli appears to last longer in duration in comparison. We hypothesize that this duration illusion, called the temporal oddball effect, is a result of the difference in expectation between the oddball and the repeated stimuli. Specifically, we conjecture that the repeated stimuli contract in duration as a result of increased predictability; these duration contractions, we suggest, result from decreased neural response amplitude with repetition, known as repetition suppression. Methodology/Principal Findings Participants viewed trials consisting of lines presented at a particular orientation (standard stimuli) followed by a line presented at a different orientation (oddball stimulus). We found that the size of the oddball effect correlates with the number of repetitions of the standard stimulus as well as the amount of deviance from the oddball stimulus; both of these results are consistent with a repetition suppression hypothesis. Further, we find that the temporal oddball effect is sensitive to experimental context – that is, the size of the oddball effect for a particular experimental trial is influenced by the range of duration distortions seen in preceding trials. Conclusions/Significance Our data suggest that the repetition-related duration contractions causing the oddball effect are a result of neural repetition suppression. More generally, subjective duration may reflect the prediction error associated with a stimulus and, consequently, the efficiency of encoding that stimulus. Additionally, we emphasize that experimental context effects need to be taken into consideration when designing duration-related tasks.
Modeling of variant copies of subunit D1 in the structure of photosystem II from Thermosynechococcus elongatus

Abstract In the cyanobacterium Thermosynechococcus elongatus BP-1, living in hot springs, the light environment directly regulates expression of genes that encode key components of the photosynthetic multi-subunit protein-pigment complex photosystem II (PSII). Light is not only essential as an energy source to power photosynthesis, but leads to formation of aggressive radicals which induce severe damage of protein subunits and organic cofactors. Photosynthetic organisms develop several protection mechanisms against this photo-damage, such as the differential expression of genes coding for the reaction center subunit D1 in PSII. Testing the expression of the three different genes (psbAI, psbAII, psbAIII) coding for D1 in T. elongatus under culture conditions used for preparing the material used in crystallization of PSII showed that under these conditions only subunit PsbA1 is present. However, exposure to high-light intensity induced partial replacement of PsbA1 with PsbA3. Modeling of the variant amino acids of the three different D1 copies in the 3.0 Å resolution crystal structure of PSII revealed that most of them are in the direct vicinity to redox-active cofactors of the electron transfer chain. Possible structural and mechanistic consequences for electron transfer are discussed.
The operad of wiring diagrams: formalizing a graphical language for databases, recursion, and plug-and-play circuits

Wiring diagrams, as seen in digital circuits, can be nested hierarchically and thus have an aspect of self-similarity. We show that wiring diagrams form the morphisms of an operad $\mcT$, capturing this self-similarity. We discuss the algebra $\Rel$ of mathematical relations on $\mcT$, and in so doing use wiring diagrams as a graphical language with which to structure queries on relational databases. We give the example of circuit diagrams as a special case. We move on to show how plug-and-play devices and also recursion can be formulated in the operadic framework as well. Throughout we include many examples and figures.
Hero turned villain: NLRP3 inflammasome‐induced inflammation during influenza A virus infection

The severity of influenza A virus (IAV) infection can range from asymptotic to mild to severe. Infections, such as those seen following outbreaks of avian IAV, are associated with hyperinflammatory responses and the development of fatal disease. There is a continual threat that a novel or pandemic IAV will circulate in humans with high rates of mortality. The neuronal apoptosis inhibitor protein, class 2 transcription activator of the MHC, heterokaryon incompatibility, telomerase‐associated protein 1, leucine‐rich repeat, and pyrin domain‐containing protein 3 (NLRP3) inflammasome is an innate immune sensor that has been shown to be critical for the secretion of the potent proinflammatory cytokines, IL‐1β and IL‐18, as well as chemokine production and cellular inflammation in vivo following IAV infection. Initial studies illustrated a protective role of NLRP3 during severe IAV infection in mice. However, the NLRP3 inflammasome may be a hero that turns villain in the later stages of severe IAV infection via the promotion of a hyperinflammatory state. Current treatments for patients who present to hospitals with a severe IAV infection are limited. The understanding of the mechanisms involved in the induction of NLRP3‐dependent inflammation during severe IAV infections may provide new therapeutic targets that reduce human mortality.
An Extended Spatio-Temporal Granger Causality Model for Air Quality Estimation with Heterogeneous Urban Big Data

This paper deals with city-wide air quality estimation with limited air quality monitoring stations which are geographically sparse. Since air pollution is influenced by urban dynamics (e.g., meteorology and traffic) which are available throughout the city, we can infer the air quality in regions without monitoring stations based on such spatial-temporal (ST) heterogeneous urban big data. However, big data-enabled estimation poses three challenges. The first challenge is data diversity, i.e., there are many different categories of urban data, some of which may be useless for the estimation. To overcome this, we extend Granger causality to the ST space to analyze all the causality relations in a consistent manner. The second challenge is the computational complexity due to processing the massive volume of data. To overcome this, we introduce the non-causality test to rule out urban dynamics that do not “Granger” cause air pollution, and the region of influence (ROI), which enables us to only analyze data with the highest causality levels. The third challenge is to adapt our grid-based algorithm to non-grid-based applications. By developing a flexible grid-based estimation algorithm, we can decrease the inaccuracies due to grid-based algorithm while maintaining computation efficiency.
Basolateral protein transport in streptolysin O-permeabilized MDCK cells

We have reconstituted polarized protein transport in streptolysin O- permeabilized MDCK cells from the TGN to the basolateral surface and to the apical surface. These transport steps are dependent on temperature, energy and exogenously supplied cytosol. Using this in vitro system we show that a whole tail peptide (WT peptide) corresponding to the cytoplasmic tail of a basolaterally sorted protein, the vesicular stomatitis virus glycoprotein (VSV G) inhibits the TGN to basolateral transport but does not affect any other transport step. Inhibition of VSV G transport to basolateral surface by WT peptide did not result in missorting of the protein to the apical surface. Mutation of the single tyrosine residue in the WT peptide reduced its inhibitory potency four- to fivefold. These results suggest that the VSV G tail physically interacts with a component of the sorting machinery. Using a cross- linking approach, we have identified proteins that associate with the cytoplasmic tail domain of VSV G. One of these polypeptides, Tin-2 (Tail interacting protein-2), associates with VSV G in the TGN, the site of protein sorting, but not in the ER nor at the cell surface. Tin- 2 does not associate with apically targeted hemagglutinin. WT peptide that inhibited the basolateral transport of VSV G also inhibited the association of Tin-2 with VSV G. Together, these properties make Tin-2 a candidate basolateral sorter. The results demonstrate the usefulness of the SLO-permeabilized cell system in dissecting the sorting machinery.
Comparison of Rapid Tests for Evaluation of Chloride Resistance of Concretes with Supplementary Cementitious Materials

AbstractIn this research, the performance of three rapid methods for evaluation of chloride resistance of concrete, including the rapid chloride penetration test (RCPT), rapid chloride migration test (RCMT), and electrical resistance test, are compared. Because the ability of the RCPT method to evaluate of concrete mixes containing supplementary cementitious materials has been questioned by some researchers, the mixes studied included the control mix and mixes containing 2.5, 5, 7.5, and 10% silica fume (SF); 7.5 and 15% fine fly ash (VFA); 15 and 30% fly ash (FA); 15 and 30% pumice (PU); and 15, 30, and 50% slag (SL). The results of all three methods show a considerable decrease in chloride permeability of mixes containing silica fume at the ages of 28 and 90 days and mixes containing other supplementary cementitious materials at 90 days. However, the RCPT test considerably overestimated the improvement compared to the other two methods, mainly as a result of the temperature rise effect in this test. Des.
DOES NICHE CONSERVATISM PROMOTE SPECIATION? A CASE STUDY IN NORTH AMERICAN SALAMANDERS

Abstract Recent speciation research has generally focused on how lineages that originate in allopatry evolve intrinsic reproductive isolation, or how ecological divergence promotes nonallopatric speciation. However, the ecological basis of allopatric isolation, which underlies the most common geographic mode of speciation, remains poorly understood and largely unstudied. Here, we explore the ecological and evolutionary factors that promote speciation in Desmognathus and Plethodon salamanders from temperate eastern North America. Based on published molecular phylogenetic estimates and the degree of geographic range overlap among extant species, we find strong evidence for a role for geographic isolation in speciation. We then examine the relationship between climatic variation and speciation in 16 sister-taxon pairs using geographic information system maps of climatic variables, new methods for modeling species' potential geographic distributions, and data on geographic patterns of genetic variation. In contrast to recent studies in tropical montane regions, we found no evidence for parapatric speciation along climatic gradients. Instead, many montane sister taxa in the Appalachian Highlands inhabit similar climatic niches and seemingly are allopatric because they are unable to tolerate the climatic conditions in the intervening lowlands. This temporal and spatial-ecological pattern suggests that niche conservatism, rather than niche divergence, plays the primary role in promoting allopatric speciation and montane endemism in this species-rich group of vertebrates. Our results demonstrate that even the relatively subtle climatic differences between montane and lowland habitats in eastern North America may play a key role in the origin of new species.
Metabolism of (2S)-Pterosin A: Identification of the Phase I and Phase II Metabolites in Rat Urine

The metabolic profile of the potent hypoglycemic agent, (2S)-pterosin A (1), in rat urine via intragastrical oral administration was investigated. In total, 19 metabolites (M1–M19) were identified. Among these, 16 metabolites were characterized by high-performance liquid chromatography solid-phase extraction-tube transfer-NMR, and seven metabolites were further isolated from the treated urine to enable further structural determination. Twelve of these are new compounds. The phase I metabolites of 1 were formed via various oxidations at positions C-3, C-10, C-12, C-13, or C-1 followed by decarboxylation of C-10 or C-14, and lactonization at C-12/C-14 or C-14/C-12. The phase II metabolites were glucuronide conjugates from the parent compound or phase I metabolites. The major metabolites were found to be (2S)-14-O-glucuronylpterosin A (M9), (2S)-2-hydroxymethylpterosin E (M14), and (±)-pterosin B (M19). Quantitative HPLC analysis of metabolites, based on similar UV absorption and use of the regression equation of 1, indicated that ∼71% 1 was excreted as metabolites in rat urine.
On Evaluation Validity in Music Autotagging

Music autotagging, an established problem in Music Information Retrieval, aims to alleviate the human cost required to manually annotate collections of recorded music with textual labels by automating the process. Many autotagging systems have been proposed and evaluated by procedures and datasets that are now standard (used in MIREX, for instance). Very little work, however, has been dedicated to determine what these evaluations really mean about an autotagging system, or the comparison of two systems, for the problem of annotating music in the real world. In this article, we are concerned with explaining the figure of merit of an autotagging system evaluated with a standard approach. Specifically, does the figure of merit, or a comparison of figures of merit, warrant a conclusion about how well autotagging systems have learned to describe music with a specific vocabulary? The main contributions of this paper are a formalization of the notion of validity in autotagging evaluation, and a method to test it in general. We demonstrate the practical use of our method in experiments with three specific state-of-the-art autotagging systems --all of which are reproducible using the linked code and data. Our experiments show for these specific systems in a simple and objective two-class task that the standard evaluation approach does not provide valid indicators of their performance.
Relapsing-remitting multiple sclerosis and whole-brain N-acetylaspartate measurement: evidence for different clinical cohorts initial observations.

PURPOSE To quantify the rate of concentration decline of neuronal marker N-acetylaspartate (NAA) in the entire brain of patients with relapsing-remitting multiple sclerosis (MS) in relation to healthy age-matched control subjects. MATERIALS AND METHODS Whole-brain NAA (WBNAA) concentration was quantified in 49 patients with relapsing-remitting MS by using magnetic resonance (MR) imaging and proton MR spectroscopy. It was statistically analyzed by using Spearman rank correlation coefficients to test the intragroup relationship between WBNAA and Expanded Disability Status Scale (EDSS) score and Mann-Whitney analyses to test for differences between subgroups' EDSS scores versus previously published WBNAA values for healthy subjects, disease duration, and age. RESULTS Analyses indicated three subgroups of WBNAA dynamics: Ten patients' conditions were "stable," exhibiting an insignificant change of about 0% (0.02/14.37) per year of clinically definite disease duration (P =.54); 27 patients showed "moderate" decline, -2.8% (-0.34/12.18) per year (P <.01); and 12 patients experienced "rapid" decline, -27.9% (-3.39/12.14) per year (P <.01). No correlation was found between WBNAA deficit, EDSS score, and age. CONCLUSION Ascertaining an individual's NAA concentration dynamics might enable early forecast of disease course, reflect disease severity and thus influence treatment decisions, and improve clinical trial efficiency by allowing selection of candidates on the basis of WBNAA dynamics in addition to clinical status.
Medical apps for smartphones: lack of evidence undermines quality and safety

Increasing numbers of healthcare professionals are using smartphones and their associated applications (apps) in daily clinical care. While these medical apps hold great potential for improving clinical practice, little is known about the possible dangers associated with their use. Breaches of patient confidentiality, conflicts of interests and malfunctioning clinical decision-making apps could all negatively impact on patient care. We propose several strategies to enhance the development of evidence-based medical apps while retaining their open nature. The increasing use of medical apps calls for broader discussion across medicine's organising and accrediting bodies. The field of medical apps is currently one of the most dynamic in medicine, with real potential to change the way evidence-based healthcare is delivered in the future. Establishing appropriate regulatory procedures will enable this potential to be fulfilled, while at all times ensuring the safety of the patient.
Factors Predicting the Efficacy of Adefovir Dipivoxil on Treatment-Naïve Chronic Hepatitis B Patients at 48 Weeks

Background/Aims To reveal possible factors predicting the effect of adefovir dipivoxil (ADV) treatment on chronic hepatitis B (CHB) and optimize the utilization of ADV. Methods In total, 168 treatment-naïve CHB patients were enrolled, including 117 hepatitis B e antigen (HBeAg)-positive patients and 51 HBeAg-negative patients who met the inclusion criteria. All patients were treated with ADV 10 mg per day for 48 weeks. Multiple logistic regression analyses were used to investigate baseline factors, and responses at weeks 12 and 24 were analyzed as predictive values. Results Multiple regression analyses showed that baseline HBeAg status and HBV DNA levels significantly affected the virological response (VR) (p<0.05), baseline ALT levels were an independent predictor of serological response (SR) (p<0.05) and the body mass index (BMI) may affect the biochemical response (BR) (p<0.05). There was a statistically significant difference in the VR and SR between patients with a primary nonresponse (PNR) at week 12 and those with a VR at week 12 (p<0.01). Additionally, the VR was significantly different between patients with HBV DNA lower than 103 copies/mL at week 24 and those with greater than 103 copies/mL (p<0.01). Conclusions Patients with negative HBeAg, lower HBV DNA levels and higher ALT values at baseline are more suitable for ADV treatment, whereas patients with lower BMIs may be more amenable to ALT normalization. Adjustments for treatment strategy should be considered if PNR at week 12 or HBV DNA ≥103 copies/mL at week 24 is observed.
Superiority of Dobutamine over Dopamine for Augmentation of Cardiac Output in Patients with Chronic Low Output Cardiac Failure

Dobutamine is a newly developed catecholamine reported to have minimal direct vascular effects relative to its inotropic activity and to have less chronotropic and arrhythmogenic properties than other catecholamines used in the treatment of low output states. In this study, the acute hemodynamic effects of dobutamine were compared to those of dopamine in 13 patients with chronic low output cardiac failure. At dosages adjusted to achieve similar increments in cardiac output, dobutamine reduced left yen tricular filling pressure (LVFP) from 25 ± 2 mm Hg (SEM) to 17 ± 2 mm Hg, while dopamine increased LVFP to 30 ± 3 mm Hg and in six patients caused arterial 02 saturation to fall below 90%. This poor response to dopamine was probably the result of its vasoconstrictive effects and illustrates the potential advantages of using a cardioselective agent such as dobutamine when the desired goal of therapy is to improve ventricular function by direct inotropic stimulation.
Does Your Configuration Code Smell?

Infrastructure as Code (IaC) is the practice of specifying computing system configurations through code, and managing them through traditional software engineering methods. The wide adoption of configuration management and increasing size and complexity of the associated code, prompt for assessing, maintaining, and improving the configuration code's quality. In this context, traditional software engineering knowledge and best practices associated with code quality management can be leveraged to assess and manage configuration code quality. We propose a catalog of 13 implementation and 11 design configuration smells, where each smell violates recommended best practices for configuration code. We analyzed 4,621 Puppet repositories containing 8.9 million lines of code and detected the cataloged implementation and design configuration smells. Our analysis reveals that the design configuration smells show 9% higher average co-occurrence among themselves than the implementation configuration smells. We also observed that configuration smells belonging to a smell category tend to co-occur with configuration smells belonging to another smell category when correlation is computed by volume of identified smells. Finally, design configuration smell density shows negative correlation whereas implementation configuration smell density exhibits no correlation with the size of a configuration management system.