bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Papillomavirus Prevalence and Integration Status in Tissue Samples of Bladder Cancer in the Chinese Population
Authors: Yan Yongji , Zhang Hongfeng , Jiang Chunfan , Ma Xin , Zhou Xueying , Tian Xun , Song Yuping , Chen Xu , Yu Liyao , Li Rui , Chen Hongwei , Wang Xin , Liu Ting , He Zhaohui , Li Hongzhao
Published: November 2020

Background

Human papillomavirus (HPV) infection is associated with multiple types of cancer, but the evidence has not yet been fully elucidated in bladder cancer.

Methods

Frozen tissue samples collected from 146 patients aged 32 to 89 years with bladder cancer pathological diagnosis between 2015 and 2019 were analyzed. HPV genotyping and integration status determination were performed by capture-based next generation sequencing. Statistical analysis of HPV type distributions was performed according to stage, grade, sex, and age group of patients.

Results

Mean (SD) age of the 146 patients was 66.64 ± 10.06 years and 83.56% were men. Overall HPV infection rate was 28.77% (37.50% in women and 27.05% in men), with 11.90% HPV integration events. Among them, 17.12% single and 11.65% coinfections were observed. HPV18 (24.66%) was the most prevalent genotype, followed by HPV33, 16, and 39. All HPV were European lineage (A). HPV16 was more prevalent in women (P = .04).

Conclusions

HPV infection may contribute to the etiology both in men and women with bladder cancer. HPV18, followed by HPV33, 16, and 39 genotypes, potentially represent the predominant oncogenic risk types for bladder carcinogenesis.
Recent advances in generalized thermoelasticity theory and the modified models: a review
Authors: Shakeriaski Farshad , Ghodrat Maryam , Escobedo-Diaz Juan , Behnia Masud
Published: November 2020

A review of the recent studies on the generalized thermoelasticity theories and their associated modified models is presented. The aim is to outline an overview of the utilization and physical limitations of available relevant theories. By contrast to classical thermoelasticity theory, generalized thermoelasticity theories (second sound) can involve a hyperbolic-form transport correlation and are motivated by experiments illustrating more accurately of the wave-form heat transfer (second sound). Many researchers have formulated such theories on different fields and analyzed various problems, presenting characteristic properties of these theories. This paper expresses a self-included bibliographical review of previous documents in the area of the second sound. The general structure of this review contains theories, formulations, real limitations, and used solution techniques of the equations for different geometries and loadings. Given that the classical theory is feeble in simulating the temperature distribution, especially in the structures under a sudden thermal shock, this review may be a useful tool for researchers who work in sensitive industries such as steam turbines, micro-temperature sensors, and lithium battery manufacturing.
Cerebrum: Modelling the Mind through Psychedelic and Playful Environments
Authors: Lovell Jonathan
Published: November 2020

This article explores Cerebrum, a hybrid of a nightclub and a gallery, which for a brief moment in the late 1960s, used the combined force of media, performance and architecture to transform a Manhattan storefront into a series of virtual realities. Described as a ‘Psychedelic Playpen’, Cerebrum became—as its name suggests—an environmental model on the contemporary discourse on altered states of consciousness. It provided an eloquent expression of Timothy Leary’s advice on how to conduct a psychedelic trip, and Marshall McLuhan’s prediction that electronic media technologies would return humanity to the playful sensuality of preliterate societies. After being attended by Gene Youngblood and Alvin Toffler, Cerebrum was cited within their respective texts—Expanded Cinema and Future Shock—as evidence within their debate upon whether the pleasure generated by such environments would be used to challenge or consolidate structures of power. The purpose of this article is to elaborate on what constituted a typical night at Cerebrum and evaluate how it contributed to the post-war debate about the psycho-social implications of immersive multimedia environments.
US Court of Appeals for the Federal Circuit finds that administrative patent judges were unconstitutionally appointed in case now the subject of multiple appeals to the US Supreme Court
Authors: Macedo Charles R , Goldberg David P , Sturm Chandler
Published: November 2020

On 31 October 2020, a three-judge panel of the US Court of Appeals for the Federal Circuit (‘Federal Circuit’) issued a decision in Arthrex, Inc v Smith & Nephew, Inc finding that administrative patent judges of the Patent Trial and Appeal Board were appointed in violation of the Appointments Clause of the US Constitution and instituting measures to remedy the situation. On 23 March 2020, the Federal Circuit refused to the rehear the case sitting en banc. Since then, the panel decision has become the subject of multiple appeals to the US Supreme Court. We expect to learn in early autumn whether the US Supreme Court decides to grant certiorari with respect to any of the appeals and review this important decision.
Extraskeletal myxoid chondrosarcoma: a case report with adjuvant intraoperative treatment
Authors: Bacchetti Stefano , Pegolo Enrico , Adani Gianluigi , Macrì Antonio , Andreetta Claudia , Ermacora Paola , Girometti Rossano , Trovò Marco , Driul Lorenza , Di Loreto Carla , Pasqual Enricomaria
Published: November 2020

Extraskeletal myxoid chondrosarcoma is a rare form of malignant mesenchymal neoplasm mainly localized into the limbs, particularly in the thigh and popliteal fossa. It has been classified as a low-grade sarcoma so far, but it shows a tendency to relapse and metastasize. In the early stage of disease, surgery represents the only chance of cure. In case of diffuse metastatic disease, systemic chemotherapy with anthracyclines is the standard of care. In this paper, we present a case of a patient affected by this rare disease and the analysis of radiological, surgical and histopathological aspects.
Incidence of Hepatotoxicity in Iranian Patients With HIV on Antiretroviral Therapies and Its Correlation with Virologic Response to HIV Treatment
Authors: Hashempour Tayebeh , Moayedi Javad , Mousavi Zahra , Esmaeli Masoumeh , Asadzadeh Azizeh , Hasanshahi Zahra , Dehghani Behzad
Published: November 2020

Objective

To investigate hepatotoxicity in Iranian patients with HIV to assess the association between virologic response to HIV treatment and serum alanine aminotransferase (ALT).

Methods

This study was conducted with 200 control patients, 75 patients with HIV naïve to antiretroviral therapy (ART), and 443 patients who received ARTs with virologic response (≤1000 copies/mL) or virologic treatment failure (>1000 copies/mL). Serum ALT level and HIV viral load were determined in all patients.

Results

Patient ALT levels were significantly higher than those of control patients (45.1 ± 44.4 IU/L vs 23.8 ± 5.4 IU/L). Compared to patients who were ART-naïve, patients with ART experience had significantly higher ALT levels (38.2 ± 26.2 IU/L vs 46.3 ± 46.7 IU/L), and severe hepatotoxicity was only detected in those with ART experience (8 patients, 1.8%). Mean ALT had no significant difference between virologic response/failure groups. The ALT activity and HIV load had a negative correlation coefficient, but it was not significant.

Conclusion

Periodic monitoring for the possibility of hepatotoxicity is highly recommended in all patients with HIV, especially in those receiving ART treatment.
The Impact of Graduate Medical Education on Scholarly Activity at a Military Medical Treatment Facility
Authors: Morris Michael J , Aden James K , Bell David G , Faux Brian M , Matos Renee I , Mu Thornton S , Valdez Michelle M , Bonjour Timothy J , True Mark W
Published: November 2020

Introduction

Graduate medical education (GME) faculty and trainees have required scholarly activities to meet accreditation requirements. The impact of this contribution to the Military Health System, especially regarding innovations in military medicine, has not been previously examined. This study measured the contribution of GME in published manuscripts from a tertiary military medical center.

Materials and Methods

Utilizing the Scopus database, published manuscripts from the primary military GME institutions for the San Antonio Uniformed Services Health Education Consortium were identified from 2008 to 2018. Manuscripts were sorted based on the number of citations in Scopus and analyzed for their overall impact in medicine to include military unique topics.

Results

A total of 3,700 manuscripts were identified through Scopus and based on a 10 citation minimum, 1,365 manuscripts were further analyzed; 1,152 (84.4%) included authors with GME affiliation and 554 (40.6%) had direct applicability to unique aspects of military medicine. The mean number of citations per manuscript was 39.2 ± 63.6; Mean Cite Score was 2.97 ± 2.14 and Field Weighted Citation Index of 2.22 ± 3.27. Analysis of number of citations (10-19; 20-39; or >40) did not show any significant differences in Cite Score or military relevance, whereas the percentage of military relevant articles remained consistent yearly.

Conclusions

These findings highlight the importance of military medical research and addressing specific medical needs of the warfighter. Graduate medical education in a tertiary Military Health System facility has enormous impact in scholarly activity, in particular the importance related to military medicine topics that emphasize combat casualty care and military readiness.
Cosmic ray transport in mixed magnetic fields and their role on the observed anisotropies
Authors: Fitz Axen Margot , Speicher Julia , Hungerford Aimee , Fryer Chris L
Published: November 2020

There is a growing set of observational data demonstrating that cosmic rays exhibit small-scale anisotropies (5°–30°) with amplitude deviations lying between 0.01–0.1 per cent that of the average cosmic ray flux. A broad range of models have been proposed to explain these anisotropies ranging from finite-scale magnetic field structures to dark matter annihilation. The standard diffusion transport methods used in cosmic ray propagation do not capture the transport physics in a medium with finite-scale or coherent magnetic field structures. Here, we present a Monte Carlo transport method, applying it to a series of finite-scale magnetic field structures to determine the requirements of such fields in explaining the observed cosmic ray, small-scale anisotropies.
Detailed chemical evolution models of the Tucana dSph galaxy
Authors: Avila-Vergara N , Carigi L , Hidalgo S L , Arrieta A
Published: November 2020

We use semi-analytical methods to obtain detailed chemical evolution models (CEMs) for the dwarf spheroidal (dSph) galaxy Tucana. Published star formation rates and the age–metallicity relationship are used to constrain the observables. The results show that Tucana: (i) behaved like a closed box for 75 per cent of its life, (ii) had either a primordial-gas accretion or a metal-rich wind during 15 per cent of its life (between 0.5 and 2.0 Gyr), and (iii) lost 95 per cent of its gas through a well-mixed wind at t ∼ 4.5 Gyr. Specifically, we find two CEMs: the metal-dilution model and the metal-loss model, which differ mainly during the range 0.5–2.0 Gyr. In order to discriminate between these CEMs, we compare the predicted [Xi/Fe]–[Fe/H] trends, which differ less than the average error of the observed trends for other dSphs of the Local Group. Furthermore, the models predict very different metallicity distribution functions. Therefore, an observational metallicity distribution function for Tucana is essential in order to discriminate between the metal-dilution and the metal-loss scenarios. In addition, because the difference of [Xi/Fe] between the two models is less than the average of the errors observed for others dSph and ultra-faint dwarf galaxies of the Local Group, greater precision is required in future observations, so that the errors are less than the difference between the models, thus enabling discrimination between them.
Revealing the relation between black hole growth and host-galaxy compactness among star-forming galaxies
Authors: Ni Q , Brandt W N , Yang G , Leja J , Chen C-T J , Luo B , Matharu J , Sun M , Vito F , Xue Y Q , Zhang K
Published: November 2020

Recent studies show that a universal relation between black hole (BH) growth and stellar mass (M⋆) or star formation rate (SFR) is an oversimplification of BH–galaxy coevolution, and that morphological and structural properties of host galaxies must also be considered. Particularly, a possible connection between BH growth and host-galaxy compactness was identified among star-forming (SF) galaxies. Utilizing ≈6300 massive galaxies with I814W  <  24 at z < 1.2 in the Cosmic Evolution Survey (COSMOS) field, we perform systematic partial correlation analyses to investigate how sample-averaged BH accretion rate ($\rm \overline{BHAR}$) depends on host-galaxy compactness among SF galaxies, when controlling for morphology and M⋆ (or SFR). The projected central surface mass density within 1 kpc, Σ1, is utilized to represent host-galaxy compactness in our study. We find that the $\rm \overline{BHAR}$–Σ1 relation is stronger than either the $\rm \overline{BHAR}$–M⋆ or $\rm \overline{BHAR}$–SFR relation among SF galaxies, and this $\rm \overline{BHAR}$–Σ1 relation applies to both bulge-dominated galaxies and galaxies that are not dominated by bulges. This $\rm \overline{BHAR}$–Σ1 relation among SF galaxies suggests a link between BH growth and the central gas density of host galaxies on the kpc scale, which may further imply a common origin of the gas in the vicinity of the BH and in the central ∼kpc of the galaxy. This $\rm \overline{BHAR}$–Σ1 relation can also be interpreted as the relation between BH growth and the central velocity dispersion of host galaxies at a given gas content (i.e. gas mass fraction), indicating the role of the host-galaxy potential well in regulating accretion on to the BH.
Mode changing, subpulse drifting, and nulling in four component conal pulsar PSR J2321+6024
Authors: Rahaman S k Minhajur , Basu Rahul , Mitra Dipanjan , Melikidze George I
Published: November 2020

In this study, we report on a detailed single pulse polarimetric analysis of the radio emission from the pulsar J2321+6024 (B2319+60) observed with the Giant Metrewave Radio Telescope, over wide frequencies ranging between 300 to 500 MHz and widely separated observing sessions. The pulsar profile shows the presence of four distinct conal components and belongs to a small group of pulsars classified as a conal quadrupole profile type. The single pulse sequence reveals the presence of three distinct emission modes, A, B, and ABN showing subpulse drifting. Besides, there were sequences when the pulsar did not show any drifting behaviour suggesting the possibility of a new emission state, which we have termed as mode C. The evolution of the mode changing behaviour was seen during the different observing sessions with different abundance as well as the average duration of the modes seen on each date. The drifting periodicities were 7.8 ± 0.3 P, 4.3 ± 0.4 P, and 3.1 ± 0.2 P in the modes A, B, and ABN, respectively, and showed large phase variations within the mode profile. The pulsar also showed the presence of orthogonal polarization modes, particularly in the leading and trailing components, which has different characteristics for the stronger and weaker pulses. However, no correlation was found between the emission modes and their polarization behaviour, with the estimated emission heights remaining roughly constant throughout. We have used the Partially Screened Gap model to understand the connection between drifting, mode changing, and nulling.
Linking globular cluster formation at low and high redshift through the age–metallicity relation in E-MOSAICS
Authors: Horta Danny , Hughes Meghan E , Pfeffer Joel L , Bastian Nate , Kruijssen J M Diederik , Reina-Campos Marta , Crain Rob A
Published: November 2020

We set out to compare the age–metallicity relation (AMR) of massive clusters from Magellanic Cloud mass galaxies in the E-MOSAICS suite of numerical cosmological simulations with an amalgamation of observational data of massive clusters in the Large and Small Magellanic Clouds (LMC/SMC). We aim to test if: (i) star cluster formation proceeds according to universal physical processes, suggestive of a common formation mechanism for young-massive clusters (YMCs), intermediate-age clusters (IACs), and ancient globular clusters (GCs); (ii) massive clusters of all ages trace a continuous AMR; and (iii) the AMRs of smaller mass galaxies show a shallower relation when compared to more massive galaxies. Our results show that, within the uncertainties, the predicted AMRs of L/SMC-mass galaxies with similar star formation histories to the L/SMC follow the same relation as observations. We also find that the metallicity at which the AMR saturates increases with galaxy mass, which is also found for the field star AMRs. This suggests that relatively low-metallicity clusters can still form in dwarfs galaxies. Given our results, we suggest that ancient GCs share their formation mechanism with IACs and YMCs, in which GCs are the result of a universal process of star cluster formation during the early episodes of star formation in their host galaxies.
Physical properties and scaling relations of molecular clouds: the impact of star formation
Authors: Grisdale Kearn
Published: November 2020

Using hydrodynamical simulations of a Milky Way-like galaxy, reaching 4.6 pc resolution, we study how the choice of star formation criteria impacts both galactic and giant molecular cloud (GMC) scales. We find that using a turbulent, self-gravitating star formation criteria leads to an increase in the fraction of gas with densities between 10 and $10^{4}{\, \rm {cm^{-3}}}$ when compared with a simulation using a molecular star formation method, despite both having nearly identical gaseous and stellar morphologies. Furthermore, we find that the site of star formation is effected with the the former tending to only produce stars in regions of very high density (${\gt}10^{4}{\, \rm {cm^{-3}}}$) gas, while the latter forms stars along the entire length of its spiral arms. The properties of GMCs are impacted by the choice of star formation criteria with the former method producing larger clouds. Despite the differences, we find that the relationships between clouds properties, such as the Larson relations, remain unaffected. Finally, the scatter in the measured star formation efficiency per free-fall time of GMCs remains present with both methods and is thus set by other factors.
A rotation-driven pulsar radio emission mechanism
Authors: Melrose D B , Rafat M Z , Mastrano A
Published: November 2020

We propose and discuss an alternative pulsar radio emission mechanism that relies on rotation-driven plasma oscillations, rather than on a beam-driven instability, and suggest that it may be the generic radio emission mechanism for pulsars. We identify these oscillations as superluminal longitudinal waves in the pulsar plasma and point out that these waves can escape directly in the O mode. We argue that the frequency of the oscillations is ω0 ≈ ωp(2〈γ〉)1/2/γs, where γs is the Lorentz factor of bulk streaming motion and 〈γ〉 is the mean Lorentz factor in the rest frame of the plasma. The dependence of the plasma frequency ωp on radial distance implies a specific frequency-to-radius mapping, ω0∝r−3/2. Escape of the energy in these oscillations is possible if they are generated in overdense, field-aligned regions that we call fibres; the wave energy is initially refracted into underdense regions between the fibres, which act as ducts. Some implications of the model for the interpretation of pulsar radio emission are discussed.
Dynamical masses of brightest cluster galaxies – II. Constraints on the stellar IMF
Authors: Loubser S I , Hoekstra H , Babul A , Bahé Y M , Donahue M
Published: November 2020

We use stellar and dynamical mass profiles, combined with a stellar population analysis, of 32 brightest cluster galaxies (BCGs) at redshifts of 0.05 ≤$z$ ≤ 0.30, to place constraints on their stellar initial mass function (IMF). We measure the spatially resolved stellar population properties of the BCGs, and use it to derive their stellar mass-to-light ratios ($\Upsilon _{\star \rm POP}$). We find young stellar populations (<200 Myr) in the centres of 22 per cent of the sample, and constant $\Upsilon _{\star \rm POP}$ within 15 kpc for 60 per cent of the sample. We further use the stellar mass-to-light ratio from the dynamical mass profiles of the BCGs ($\Upsilon _{\star \rm DYN}$), modelled using a multi-Gaussian expansion and Jeans Anisotropic Method, with the dark matter contribution explicitly constrained from weak gravitational lensing measurements. We directly compare the stellar mass-to-light ratios derived from the two independent methods, $\Upsilon _{\star \rm POP}$ (assuming some IMF) to $\Upsilon _{\star \rm DYN}$ for the subsample of BCGs with no young stellar populations and constant $\Upsilon _{\star \rm POP}$. We find that for the majority of these BCGs, a Salpeter (or even more bottom-heavy) IMF is needed to reconcile the stellar population and dynamical modelling results although for a small number of BCGs, a Kroupa (or even lighter) IMF is preferred. For those BCGs better fit with a Salpeter IMF, we find that the mass-excess factor against velocity dispersion falls on an extrapolation (towards higher masses) of known literature correlations. We conclude that there is substantial scatter in the IMF amongst the highest mass galaxies.
The study of multipeaked type-I X-ray bursts in the neutron star low-mass X-ray binary 4U 1636 − 536 with RXTE
Authors: Li Chen , Zhang Guobao , Méndez Mariano , Wang Jiancheng , Lyu Ming
Published: November 2020

We have found and analysed 16 multipeaked type-I bursts from the neutron-star low-mass X-ray binary 4U 1636 − 53 with the Rossi X-ray Timing Explorer (RXTE). One of the bursts is a rare quadruple-peaked burst that was not previously reported. All 16 bursts show a multipeaked structure not only in the X-ray light curves but also in the bolometric light curves. Most of the multipeaked bursts appear in observations during the transition from the hard to the soft state in the colour–colour diagram. We find an anticorrelation between the second peak flux and the separation time between two peaks. We also find that in the double-peaked bursts the peak-flux ratio and the temperature of the thermal component in the pre-burst spectra are correlated. This indicates that the double-peaked structure in the light curve of the bursts may be affected by enhanced accretion rate in the disc, or increased temperature of the neutron star.
Machines learn to infer stellar parameters just by looking at a large number of spectra
Authors: Sedaghat Nima , Romaniello Martino , Carrick Jonathan E , Pineau François-Xavier
Published: November 2020

Machine learning has been widely applied to clearly defined problems of astronomy and astrophysics. However, deep learning and its conceptual differences to classical machine learning have been largely overlooked in these fields. The broad hypothesis behind our work is that letting the abundant real astrophysical data speak for itself, with minimal supervision and no labels, can reveal interesting patterns that may facilitate discovery of novel physical relationships. Here, as the first step, we seek to interpret the representations a deep convolutional neural network chooses to learn, and find correlations in them with current physical understanding. We train an encoder–decoder architecture on the self-supervised auxiliary task of reconstruction to allow it to learn general representations without bias towards any specific task. By exerting weak disentanglement at the information bottleneck of the network, we implicitly enforce interpretability in the learned features. We develop two independent statistical and information-theoretical methods for finding the number of learned informative features, as well as measuring their true correlation with astrophysical validation labels. As a case study, we apply this method to a data set of ∼270 000 stellar spectra, each of which comprising ∼300 000 dimensions. We find that the network clearly assigns specific nodes to estimate (notions of) parameters such as radial velocity and effective temperature without being asked to do so, all in a completely physics-agnostic process. This supports the first part of our hypothesis. Moreover, we find with high confidence that there are ∼4 more independently informative dimensions that do not show a direct correlation with our validation parameters, presenting potential room for future studies.
Evolution of Embryo Implantation Was Enabled by the Origin of Decidual Stromal Cells in Eutherian Mammals
Authors: Chavan Arun R , Griffith Oliver W , Stadtmauer Daniel J , Maziarz Jamie , Pavlicev Mihaela , Fishman Ruth , Koren Lee , Romero Roberto , Wagner Günter P
Published: November 2020

Mammalian pregnancy evolved in the therian stem lineage, that is, before the common ancestor of marsupials and eutherian (placental) mammals. Ancestral therian pregnancy likely involved a brief phase of attachment between the fetal and maternal tissues followed by parturition—similar to the situation in most marsupials including the opossum. In all eutherians, however, embryo attachment is followed by implantation, allowing for a stable fetal–maternal interface and an extended gestation. Embryo attachment induces an attachment reaction in the uterus that is homologous to an inflammatory response. Here, we elucidate the evolutionary mechanism by which the ancestral inflammatory response was transformed into embryo implantation in the eutherian lineage. We performed a comparative uterine transcriptomic and immunohistochemical study of three eutherians, armadillo (Dasypus novemcinctus), hyrax (Procavia capensis), and rabbit (Oryctolagus cuniculus); and one marsupial, opossum (Monodelphis domestica). Our results suggest that in the eutherian lineage, the ancestral inflammatory response was domesticated by suppressing one of its modules detrimental to pregnancy, namely, neutrophil recruitment by cytokine IL17A. Further, we propose that this suppression was mediated by decidual stromal cells, a novel cell type in eutherian mammals. We tested a prediction of this model in vitro and showed that decidual stromal cells can suppress the production of IL17A from helper T cells. Together, these results provide a mechanistic understanding of early stages in the evolution of eutherian pregnancy.
Staying true to yourself: mechanisms of DNA methylation maintenance in mammals
Authors: Petryk Nataliya , Bultmann Sebastian , Bartke Till , Defossez Pierre-Antoine
Published: November 2020

DNA methylation is essential to development and cellular physiology in mammals. Faulty DNA methylation is frequently observed in human diseases like cancer and neurological disorders. Molecularly, this epigenetic mark is linked to other chromatin modifications and it regulates key genomic processes, including transcription and splicing. Each round of DNA replication generates two hemi-methylated copies of the genome. These must be converted back to symmetrically methylated DNA before the next S-phase, or the mark will fade away; therefore the maintenance of DNA methylation is essential. Mechanistically, the maintenance of this epigenetic modification takes place during and after DNA replication, and occurs within the very dynamic context of chromatin re-assembly. Here, we review recent discoveries and unresolved questions regarding the mechanisms, dynamics and fidelity of DNA methylation maintenance in mammals. We also discuss how it could be regulated in normal development and misregulated in disease.
CRISPRidentify: identification of CRISPR arrays using machine learning approach
Authors: Mitrofanov Alexander , Alkhnbashi Omer S , Shmakov Sergey A , Makarova Kira S , Koonin Eugene V , Backofen Rolf
Published: November 2020

CRISPR–Cas are adaptive immune systems that degrade foreign genetic elements in archaea and bacteria. In carrying out their immune functions, CRISPR–Cas systems heavily rely on RNA components. These CRISPR (cr) RNAs are repeat-spacer units that are produced by processing of pre-crRNA, the transcript of CRISPR arrays, and guide Cas protein(s) to the cognate invading nucleic acids, enabling their destruction. Several bioinformatics tools have been developed to detect CRISPR arrays based solely on DNA sequences, but all these tools employ the same strategy of looking for repetitive patterns, which might correspond to CRISPR array repeats. The identified patterns are evaluated using a fixed, built-in scoring function, and arrays exceeding a cut-off value are reported. Here, we instead introduce a data-driven approach that uses machine learning to detect and differentiate true CRISPR arrays from false ones based on several features. Our CRISPR detection tool, CRISPRidentify, performs three steps: detection, feature extraction and classification based on manually curated sets of positive and negative examples of CRISPR arrays. The identified CRISPR arrays are then reported to the user accompanied by detailed annotation. We demonstrate that our approach identifies not only previously detected CRISPR arrays, but also CRISPR array candidates not detected by other tools. Compared to other methods, our tool has a drastically reduced false positive rate. In contrast to the existing tools, our approach not only provides the user with the basic statistics on the identified CRISPR arrays but also produces a certainty score as a practical measure of the likelihood that a given genomic region is a CRISPR array.
Urine proteomics for prediction of disease progression in patients with IgA nephropathy
Authors: Rudnicki Michael , Siwy Justyna , Wendt Ralph , Lipphardt Mark , Koziolek Michael J , Maixnerova Dita , Peters Björn , Kerschbaum Julia , Leierer Johannes , Neprasova Michaela , Banasik Miroslaw , Sanz Ana Belen , Perez-Gomez Maria Vanessa , Ortiz Alberto , Stegmayr Bernd , Tesar Vladimir , Mischak Harald , Beige Joachim , Reich Heather N ,   PERSTIGAN working group, Beige Joachim , Wendt Ralph , Siwy Justyna , Zürbig Petra , Mischak Harald , Durban Annika , Raad Julia , Golovko Igor , Reich Heather , Lam Ping , Yang Stuart , Díaz Jiménez , Sanz Ana Belen , Fernandez-Fernandez Beatriz , Rojas-Rivera Jorge Enrique , Perez-Gomez Maria Vanessa , Ortiz Alberto , Sanchez-Niño Maria Dolores , Sanchez-Rodriguez Jinny , Rudnicki Michael , Kerschbaum Julia , Leierer Johannes , Mayer Gert , Stegmayr Bernd , Peters Björn
Published: November 2020

Background

Risk of kidney function decline in immunoglobulin A (IgA) nephropathy (IgAN) is significant and may not be predicted by available clinical and histological tools. To serve this unmet need, we aimed at developing a urinary biomarker-based algorithm that predicts rapid disease progression in IgAN, thus enabling a personalized risk stratification.

Methods

In this multicentre study, urine samples were collected in 209 patients with biopsy-proven IgAN. Progression was defined by tertiles of the annual change of estimated glomerular filtration rate (eGFR) during follow-up. Urine samples were analysed using capillary electrophoresis coupled mass spectrometry. The area under the receiver operating characteristic curve (AUC) was used to evaluate the risk prediction models.

Results

Of the 209 patients, 64% were male. Mean age was 42 years, mean eGFR was 63 mL/min/1.73 m2 and median proteinuria was 1.2 g/day. We identified 237 urine peptides showing significant difference in abundance according to the tertile of eGFR change. These included fragments of apolipoprotein C-III, alpha-1 antitrypsin, different collagens, fibrinogen alpha and beta, titin, haemoglobin subunits, sodium/potassium-transporting ATPase subunit gamma, uromodulin, mucin-2, fractalkine, polymeric Ig receptor and insulin. An algorithm based on these protein fragments (IgAN237) showed a significant added value for the prediction of IgAN progression [AUC 0.89; 95% confidence interval (CI) 0.83–0.95], as compared with the clinical parameters (age, gender, proteinuria, eGFR and mean arterial pressure) alone (0.72; 95% CI 0.64–0.81).

Conclusions

A urinary peptide classifier predicts progressive loss of kidney function in patients with IgAN significantly better than clinical parameters alone.
Measuring the efficiency of VAT reforms: a demand system simulation approach
Authors: Tóth Peter , Cupák Andrej , Rizov Marian
Published: November 2020

Using an estimated demand model, we simulate household-level demand responses to the recent Slovak value added tax (VAT) reform and its hypothetical alternatives. We use simulation results, instead of the standard approximate measures, for constructing an improved efficiency indicator of tax reforms as a ratio of welfare and fiscal revenue effects and call it marginal welfare gain (MWG). We also contribute to the literature on optimal structure of indirect taxes and on marginal tax reforms with new evidence of actual and hypothetical reforms that could increase the welfare of households at zero fiscal costs. Regarding the general policy implications of our results, we conclude that using a demand model to rank commodities according to their MWGs can be helpful for designing both efficient and equitable VAT reforms.
Functional Group Oxidation and Reduction
Authors: Taber Douglass F.
Published: November 2020

Debabrata Maiti of the Indian Institute of Technology Bombay found (Chem. Commun. 2012, 48, 4253) that the relatively inexpensive Pd(OAc)2 effectively catalyzed the decarbonylation of an aldehyde 1 to the hydrocarbon 2. Hui Lou of Zhejiang University used (Adv. Synth. Catal. 2011, 353, 2577) a Mo catalyst to effect reduction of the ester 3 to the hydrocarbon 4, with retention of all the skeletal carbons. Jon T. Njardarson of the University of Arizona showed (Chem. Commun. 2012, 48, 7844) that the allylic ether 5 could be reduced with high regioselectivity to give 6. José Barluenga and Carlos Valdés of the Universidad de Oviedo effected (Angew. Chem. Int. Ed. 2012, 51, 5950) the direct conversion of a ketone 7 to the azide 8. Although no cyclic ketones were included in the examples, there is a good chance that this will be the long-sought diastereoselective reduction of a cyclohexanone to the equatorial amine. Hideo Nagashima of Kyushu University reduced (Chem. Lett. 2012, 41, 229) the acid 9 directly to the aldehyde 1 using a ruthenium catalyst with the bis silane 10. Georgii I. Nikonov of Brock University described (Adv. Synth. Catal. 2012, 354, 607) a similar Ru-mediated silane reduction of an acid chloride to the aldehyde. Professor Nagashima used (Angew. Chem. Int. Ed. 2012, 51, 5363) his same Ru catalyst to reduce the ester 11 to the protected amine 12. Shmaryahu Hoz of Bar-Ilan University used (J. Org. Chem. 2012, 77, 4029) photostimulation to promote the SmI2-mediated reduction of a nitrile 13 to the amine 14. Bakthan Singaram of the University of California, Santa Cruz effected (J. Org. Chem. 2012, 77, 221) the same transformation with InCl3/NaBH4. David J. Procter of the University of Manchester described (J. Org. Chem. 2012, 77, 3049) what promises to be a general method for activating Sm metal to form SmI2. Mark T. Hamann of the University of Mississippi directly reduced (J. Org. Chem. 2012, 77, 4578) the nitro group of 15 to the alkylated amine 16. Cleanly oxidizing aromatic methyl groups to the level of the aldehyde without overoxidation has been a challenge.
Functional Group Protection
Authors: Lambert Tristan H.
Published: November 2020

Alfonso Iadonisi at the University of Naples Federico II developed (Eur. J. Org. Chem. 2013, 3137) a procedure for the selective acetolysis of the perbenzylated sugar 1 to furnish 3 using isopropenyl acetate (2) instead of the more typical and high-boiling acetic anhydride. The (3,4-dimethoxylphenyl)benzyl (DMPBn) protecting group, which is removed (cf. 4 → 5) under acidic conditions in the presence of the cation scavenger 5, was developed (J. Org. Chem. 2013, 78, 5264) by David S. Larsen at the University of Otago as an alternative to the p-methoxybenzyl (PMB) group. Another new hydroxyl-protecting group, the AzDMB group, which can be installed by simple acylation of (7 + 8 → 9) and removed under reductive conditions, was developed by Gijsbert A. van der Marel and Jeroen D.C. Codée of Leiden University. Stefan Grimme at the University of Bonn and Armido Studer at Westfälische-Wilhelms-Universität Münster found (Chem. Sci. 2013, 4, 2177) that NHC precatalyst 11 in the presence of NaH, benzaldehyde, and the oxidant 12 allows for the selective O-acylation of aminoalcohol 10 to 13. The reductive deprotection of benzyl carbamate 14 using the strong organic reductant 15 under photolytic conditions was achieved (Angew. Chem. Int. Ed. 2013, 52, 2239) by John A. Murphy at the University of Strathclyde. Liang-Qiu Lu and Wen-Jing Xiao at Central China Normal University found (Chem. Asian J. 2013, 8, 1090) that mixed imide 17 could be detosylated under visible light photoredox catalysis in the presence of Hantzsch ester 18. Frank Glorius at Westfälische-Wilhelms-Universität Münster developed (Org. Lett. 2013, 15, 1776) a ruthenium-catalyzed procedure for the N-formylation of amine 20 using methanol as the source of the formyl group. Protection of the thymine derivative 22 with a 2-(methoxycarbonyl)ethenyl (MocVinyl) group to produce 23 was developed (J. Org. Chem. 2013, 78, 5832) by Jaume Vilarrasa at the University of Barcelona. Deprotection of the MocVinyl group is readily achieved by treatment with a nucleophilic reagent such as pyrrolidine. Robert H. Grubbs at Caltech demonstrated (Chem. Sci. 2013, 4, 1640) that ether 24 could be demethylated with triethylsilane and potassium t-butoxide at high temperatures.
Reactions of Alkenes: The RajanBabu Synthesis of Pseudopterosin G-J Aglycone Dimethyl Ether
Authors: Taber Douglass F.
Published: November 2020

Xiangge Zhou of Sichuan University showed (Tetrahedron Lett. 2011, 52, 318) that even the monosubstituted alkene 1 was smoothly converted to the methyl ether 2 by catalytic FeCl3. Brian C. Goess of Furman University protected (J. Org. Chem. 2011, 76, 4132) the more reactive alkene of 3 as the 9-BBN adduct, allowing selective reduction of the less reactive alkene to give, after reoxidation, the monoreduced 4. Nobukazu Taniguchi of the Fukushima Medical University added (Synlett 2011, 1308) Na p-toluenesulfinate oxidatively to 1 to give the sulfone 5. Krishnacharya G. Akamanchi of the Indian Institute of Chemical Technology, Mumbai oxidized (Synlett 2011, 81) 1 directly to the bromo ketone 6. Osmium is used catalytically both to effect dihydroxylation, to prepare 8, and to mediate oxidative cleavage, as in the conversion of 7 to the dialdehyde 9. Ken-ichi Fujita of AIST Tsukuba devised (Tetrahedron Lett. 2011, 52, 3137) magnetically retrievable osmium nanoparticles that can be reused repeatedly for the dihydroxylation. B. Moon Kim of Seoul National University established (Tetrahedron Lett. 2011, 52, 1363) an extraction scheme that allowed the catalytic Os to be reused repeatedly for the oxidative cleavage. Maurizio Taddei of the Università di Siena showed (Synlett 2011, 199) that aqueous formaldehyde could be used in place of Co/H2 (syngas) for the formylation of 1 to 10. Hirohisa Ohmiya and Masaya Sawamura of Hokkaido University prepared (Org. Lett. 2011, 13, 1086) carboxylic acids (not illustrated) from alkenes using CO2. Joseph M. Ready of the University of Texas Southwestern Medical Center selectively arylated (Angew. Chem. Int. Ed. 2011, 50, 2111) the homoallylic alcohol 11 to give 12. Many reactions of alkenes are initiated by hydroboration, then conversion of the resulting alkyl borane. Hiroyuki Kusama of the Tokyo Institute of Technology photolyzed (J. Am. Chem. Soc. 2011, 133, 3716) 14 with 13 to give the ketone 15. William G. Ogilvie of the University of Ottawa added (Synlett 2011, 1113) the 9-BBN adduct from 1 to 16 to give 17. Professors Ohmiya and Sawamura effected (Org. Lett. 2011, 13, 482) a similar conjugate addition, not illustrated, of 9-BBN adducts to α,β-unsaturated acyl imidazoles.
Arrays of Stereogenic Centers: The Barker Synthesis of (+)-Galbelgin
Authors: Taber Douglass F.
Published: November 2020

Gang Zhao of the Shanghai Institute of Organic Chemistry and Gang Zou of the East China University of Science and Technology devised (Adv. Synth. Catal. 2011, 353, 3129) an elegant catalyst for the direct enantioselective epoxidation of a simple acyclic enone 1. Ismail Ibrahem and Armando Córdova of Mid Sweden University and Stockholm University prepared (Adv. Synth. Catal. 2011, 353, 3114) 6 by combining three catalysts to effect the enantioselective addition of 5 to 4. Giovanni Casiraghi and Franca Zanardi of the Università degli Studi di Parma used (J. Org. Chem. 2011, 76, 10291) a silver catalyst to mediate the addition of 8 to 7 to give 9. Keiji Maruoka of Kyoto University condensed (Nature Chem. 2011, 3, 642) the diazo ester 10 with an aldehyde 4, leading, after reduction of the initial adduct and protection, to the diamine 11. Christoph Schneider of the Universität Leipzig effected (Synthesis 2011, 4050) the vinylogous addition of 13 to an imine 12, setting both stereogenic centers of 14. In the course of the coupling of 16 with the diol 15, Michael J. Krische of the University of Texas established (J. Am. Chem. Soc. 2011, 133, 12795) four new stereogenic centers. By adding (Chem. Commun. 2011, 47, 10557) an α-nitro ester 18 to the maleimide 19, Professor Maruoka established both the alkylated secondary center and the N-substituted quaternary center of 20. Srinivas Hotha of the Indian Institute of Science Education & Research and Torsten Linker of the University of Potsdam showed (Chem. Commun. 2011, 47, 10434) that the readily prepared lactone 21 could be opened to 23 without disturbing the stereogenic center adjacent to the carbonyls. Allan D. Headley and Bukuo Ni of Texas A&M University-Commerce devised (Synthesis 2011, 1993) a recyclable catalyst for the addition of an aldehyde 7 to a nitroalkene 24 in water to give 25. Alexandre Alexakis of the University of Geneva effected (Chem. Commun. 2011, 47, 7212) the triply convergent coupling of 26, 27, and 28 to give 29 as a single dominant diastereomer.
Arrays of Stereogenic Centers: The Carbery Synthesis of Mycestericin G
Authors: Taber Douglass F.
Published: November 2020

Chi-Ming Che of the University of Hong Kong devised (Chem. Commun. 2011, 47, 11204) a manganese catalyst for the enantioselective cis-dihydroxylation of electron-deficient alkenes such as 1. Christine Greck of Université de Versailles-St-Quentin effected (Tetrahedron Lett. 2012, 53, 1085) enantioselective alkoxylation of 3, remarkably without β-elimination. Keiji Maruoka of Kyoto University developed (J. Am. Chem. Soc. 2012, 134, 7516) an organocatalyst for the enantioselective anti addition of 5 to 6 to give 7. Barry M. Trost of Stanford University developed (J. Am. Chem. Soc. 2012, 134, 2075) a Mg catalyst for the enantioselective addition of ethyl diazoacetate to an aldehyde 8, and carried the adduct onto 9. Professor Maruoka designed (Angew. Chem. Int. Ed. 2012, 51, 1187) for the enantioselective addition of a ketone 10 to the alkynyl ketone 11 to give 12. Naoya Kumagai and Masakatsu Shibasaki of the Institute of Microbial Chemistry found (Org. Lett. 2012, 14, 3108) that 14 could be added under very soft conditions to 13 to give the anti adduct 15. René Peters of the Universität Stuttgart added (Adv. Synth. Catal. 2012, 354, 1443) the azlactone formed in situ to 17 in a conjugate sense to give 18. Kaïss Aouadi and Jean-Pierre Praly of the Université de Lyon prepared (Tetrahedron Lett. 2012, 53, 2817) the nitrone 19 from the inexpensive (–)-menthone. Dipolar cycloaddition to a range of alkenes proceeded with substantial diastereocontrol, as illustrated for 20, which gave the crystalline adduct 21. Jeffrey S. Johnson of the University of North Carolina reduced (J. Am. Chem. Soc. 2012, 134, 7329) the α-keto ester 22 under equilibrating conditions to give the lactone 23. Claudio Palomo of the Universidad del País Vasco alkylated (J. Org. Chem. 2012, 77, 747) the aldehyde 24 with 25 to give the diester 26. Damien Bonne and Jean Rodriguez of Aix-Marseille Université added (Adv. Synth. Catal. 2012, 354, 563) the α-keto ester 27 to 28 in a conjugate sense to give 29. Glenn C. Micalizio of Scripps/Florida developed (Angew. Chem. Int. Ed. 2012, 51, 5152) a general strategy for the stereocontrolled construction of skipped-conjugate dienes such as 30.
C–O Ring Construction: (+)-Varitriol (Liu), (+)-Isatisine A (Panek), (+)-Herboxidiene/GEX1A (Ghosh), (–)-Englerin A (Chain), Platensimycin (Lear/Wright)
Authors: Taber Douglass F.
Published: November 2020

En route to (+)-varitriol 4, Xue-Wei Liu of Nanyang Technological University coupled (Org. Lett. 2011, 13, 42) the glycosyl fluoride derived from 1 with the alkynyl fluoroborate salt 2 to give 3. James S. Panek of Boston University condensed (Org. Lett. 2011, 13, 502) the enantiomerically pure allyl silane 6 with the aldehyde 5 to give the tetrahydrofuran 7. Further elaboration led to (+)-isatisine A 8, the only alkaloid so far isolated from the roots and leaves of the traditional Asian folk medicine Isatis indigotica. Arun K. Ghosh of Purdue University effected (Org. Lett. 2011, 13, 66) oxidative ring expansion of the enantiomerically pure furan 9 to give, after reduction, the enone 10. This established the tetrahydropyran of (+)-herboxidiene 11, also known as GEXIA. William J. Chain of the University of Hawaii observed (J. Am. Chem. Soc. 2011, 133, 6553) unusual diastereoselectivity in the conjugate addition of the enone 12 to the enantiomerically pure aldehyde 13. Although eight diastereomers could have been formed, the reaction mixture was 2/3 the diastereomer 14. Reductive cyclization (SmI2) of 14 then led to (–)-englerin A 15. Martin J. Lear of the National University of Singapore cyclized (Org. Lett. 2010, 12, 5510) the enantiomerically pure lactol 16 to 17 with catalytic Bi(OTf)3. Dennis L. Wright of the University of Connecticut prepared (Org. Lett. 2011, 13, 2263) 21 by dipolar cycloaddition of 20 to 19. Both 17 and 21 were carried on via intramolecular alkylation toward platensimycin 18.