bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis and grading of pancreatic neuroendocrine tumors: a retrospective analysis of 110 cases
Authors: Paiella Salvatore , Landoni Luca , Rota Roberta , Valenti Matteo , Elio Giovanni , Crinò Stefano Francesco , Manfrin Erminia , Parisi Alice , Cingarlini Sara , D’Onofrio Mirko , Scarpa Aldo , Lawlor Rita Teresa , Bernardoni Laura , Capelli Paola , Nessi Chiara , Miotto Marco , Gabbrielli Armando , Bassi Claudio , Salvia Roberto
Published: June 2020

Background Data on the reliability of the Ki-67 index and grading calculations from endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic neuroendocrine tumors (PanNETs) are controversial. We aimed to assess the accuracy of these data compared with histology.

Methods Cytological analysis from EUS-FNA in patients with suspected PanNETs (n = 110) were compared with resection samples at a single institution. A minimum of 2000 cells were considered to be adequate for grading. Correlation and agreement between cytology and histology in grading and Ki-67 values, respectively, were investigated. Secondary outcomes included the diagnostic performance of EUS-FNA.

Results EUS-FNA samples were adequate for PanNET diagnosis and PanNET grading in 98/110 (89.1 %) and 77/110 (70.0 %) patients, respectively; thus, 77 samples were adequate for comparing cytology vs. histology. There were 67 (62.0 %), 40 (36.4 %), and 1 (0.9 %) patients with a final diagnosis of G1, G2, and G3 tumors, respectively. EUS-FNA grading was concordant with surgical pathology in 81.8 % of patients; under- and overgrading occurred in 15.6 % and 2.6 %, respectively. The overall level of agreement for grading was moderate (Cohen’s κ = 0.59, 95 % confidence interval [CI] 0.34 – 0.78). Spearman’s rho for Ki-67 in tumors ≤ 20 mm and > 20 mm was strong and moderate, respectively (rho = 0.68, 95 %CI 0.47 – 0.83; rho = 0.59, 95 %CI 0.35 – 0.75). The Bland – Altman plot showed that the Ki-67 values were comparable and reproducible between the two measurements.

Conclusions Although they were not available for a significant number of patients, grading and Ki-67 values from cytology correlated with histology moderately to strongly.
Evolution of a Cycloaddition–Rearrangement Approach to the Squalestatins: A Quarter-Century Odyssey
Authors: Hodgson David M. , Almohseni Hasanain A. A.
Published: June 2020

The highs, lows, and diversions of a journey leading to two syntheses of 6,7-dideoxysqualestatin H5 is described. Both syntheses relied on highly diastereoselective n-alkylations of a tartrate acetonide enolate and subsequent oxidation–hydrolysis to provide an asymmetric entry to β-hydroxy-α-ketoester motifs. The latter were differentially elaborated to diazoketones which underwent stereo- and regioselective Rh(II)-catalysed cyclic carbonyl ylide formation–cycloaddition and then acid-catalysed transketalisation to generate the 2,8-dioxabicyclo[3.2.1]octane core of the squalestatins/zaragozic acids at the correct tricarboxylate oxidation level. The unsaturated side chain was either protected with a bromide substituent during the transketalisation or introduced afterwards by a stereoretentive Ni-catalyzed Csp3–Csp2 cross-electrophile coupling.

1 Introduction  

2 Racemic Model Studies to the Squalestatin/Zaragozic Acid Core

3 Asymmetric Model Studies to a Keto α-Diazoester

3.1 Dialkyl Squarate Desymmetrisation

3.2 Tartrate Alkylation

3.2.1 Further Studies on Seebach’s Alkylation Chemistry 

4 Failure at the Penultimate Step to DDSQ 

5 Second-Generation Approach to DDSQ: A Bromide Substituent Strategy 

5.1 Stereoselective Routes to E-Alkenyl Halides via β-Oxido Phosphonium Ylides 

5.2 Back to DDSQ Synthesis

6 An Alternative Strategy to DDSQ: By Cross-Electrophile Coupling

7 Alkene Ozonolysis in the Presence of Diazo Functionality: Accessing α-Ketoester Intermediates

8 Summary
Prevalence and Awareness of Stroke and Other Comorbidities Associated with Diabetes in Northwest India
Authors: Podder Vivek , Srivastava Vinod , Kumar Saurabh , Nagarathna Raghuram , Sivapuram Madhava Sai , Kaur Navneet , Sharma Kanupriya , Singh Amit Kumar , Malik Neeru , Anand Akshay , Nagendra Hongasandra R.
Published: June 2020

Objectives The main purpose of this study is to investigate the prevalence of comorbid conditions in diabetic, prediabetic, and nondiabetic individuals. Additionally, the current study examines the levels of awareness of those comorbidities among North Indian population.

Methods As a part of a national study (Niyantrit Madhumeh Bharat [NMB] screening program), different comorbidity parameters were screened in the northern part of India between April and September 2017. There were 1,215 participants recruited in this study. Biochemical analyses of hemoglobin A1c (HbA1c) were conducted on the study subjects. Subsequently, the study subjects were divided into diabetic, prediabetic, and nondiabetic groups based on their HbA1c results.

Results The study analysis reveals a higher prevalence of peripheral vascular disease (21.2%), ocular diseases (18%), and hypertension (13.4%) in diabetics with other comorbidities. Furthermore, the study found that a vast majority of the participants were unaware of the presence of hypertension (67.2%), dyslipidemia (84.5%), kidney disease (95.2%), peripheral vascular disease (34.5%), and stroke (95.1%).

Conclusion The study concluded that in the northern India, the prevalence of multiple comorbid conditions, such as peripheral vascular disease and hypertension, is higher among diabetic population. Also, the level of awareness of diabetic comorbidities is surprisingly low, which has implications for policymakers, health practitioners, and educators of alternate medicine to increase awareness about diabetes, comorbid conditions, health risk, and possible solution at community and rural level, such as periodic screening programs in this population.
Platelet to Lymphocyte Ratio and Neutrophil to Lymphocyte Ratio in Missed Abortion
Authors: Biyik Ismail , Albayrak Mustafa , Keskin Fatih
Published: June 2020

Objective Missed abortion occurs in ∼ 15% of all clinical pregnancies. The pathogenesis is not clearly known. However, defective placentation resulting in maternal systemic inflammatory response is considered responsible for missed abortion. Platelet lymphocyte ratio (PLR) and neutrophil lymphocyte ratio (NLR) are increasingly cited parameters of inflammation in the literature. However, no study evaluated the PLR and NLR rates in missed abortions so far. The aim of the present study is to investigate whether complete blood count (CBC) inflammatory parameters such as NLR and PLR are increased in patients with missed abortion.

Methods Medical records of 40 pregnant women whose gestation ended in missed abortion at between 6 and14 weeks of gestation and of 40 healthy pregnant women were collected and compared retrospectively. The groups were compared regarding hemoglobin, hematocrit, platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), PLR and NLR.

Results Platelet distribution width, NLR and PLR values were higher in the missed abortion group compared with the healthy pregnant women group (rates are p = 0.043; p = 0.038; and p = 0.010, respectively). Hematocrit, MPV, and lymphocyte values were found to be lower in the missed abortion group compared with the healthy pregnant women group (p = 0.027, p = 0.044 and p = 0.025, respectively).

Conclusion The PDW, NLR and PLR values of the missed abortion group were reported high; and MPV values were reported low in the present study. These findings may help to speculate a defective placentation in the pathogenesis of missed abortion.
Guidelines for Management of Neurosurgical Cases during COVID-19 Pandemic
Authors: Kumar Raj , Mahapatra Ashok Kumar , Mittal Radhe Shyam , Prajapati Hanuman Prasad
Published: June 2020

Transmission of Coronavirus Disease 2019 (COVID-19) infection can occur to health care workers while providing treatment. It is vital to ensure the safety and to avoid any undue exposure of health care workers, leading to collapse of the entire health care system. As the world is facing this grave threat due to COVID-19, a proper protocol should be there. Daily updates and modifications are being made available by the Ministry of Health & Family Welfare and the ministry advises that protocols be tailored as per prevailing local conditions. We are trying to lay down guidelines based on available literature, data, and guidelines to take the procedures of neurosurgery and neurosciences.
Impact of byproducts formed on a 4H–SiC surface on interface state density of Al2O3/4H–SiC(0001) gate stacks
Authors: Doi Takuma , Shibayama Shigehisa , Takeuchi Wakana , Sakashita Mitsuo , Taoka Noriyuki , Shimizu Mitsuaki , Nakatsuka Osamu
Published: June 2020

The impact of byproducts formed on a 4H–SiC(0001) surface by substrate oxidation on the interface state density (Dit) of Al2O3/4H–SiC gate stacks was investigated in this study, because some C-related byproducts are predicted to have defect states near the conduction band minimum (EC) of 4H–SiC. At first, by developing an in situ cyclic metal layer oxidation method, we realized the formation of an Al2O3/4H–SiC gate stack without substrate oxidation, which was verified using conventional X-ray photoelectron spectroscopy (XPS). Then, the amount of byproducts on the 4H–SiC surface was controlled by chemical etching of thermally oxidized 4H–SiC. The results showed that the Dit near the EC of 4H–SiC for the Al2O3/4H–SiC gate stack increased with the amount of byproducts until it fully covered the 4H–SiC surface; thereafter, it did not increase. For the sample with byproducts below the detection limit of XPS, a Dit value as low as 5 × 1011 cm−2 eV−1 at around EC − 0.15 eV of 4H–SiC was obtained.
Correlation of exchange-bias effect with negative magnetization in perovskite compound, La0.5Pr0.5CrO3
Authors: Deepak  , Kumar A. , Yusuf S. M.
Published: June 2020

Detailed investigations of the negative magnetization (NM) phenomenon and associated exchange bias (EB) effect in a single phase perovskite compound, La0.5Pr0.5CrO3, have been carried out. DC magnetization measurement under 200 Oe reveals a magnetic ordering (TN) at 264 K and a magnetization compensation at temperature, TCOMP ∼ 160 K. The compound exhibits NM as well as EB below TCOMP. The temperature and cooling field dependencies of EB have been investigated to reveal the dominant antiferromagnetic (AFM) and ferromagnetic (FM) interactions in La0.5Pr0.5CrO3. Both positive horizontal (HEB) and negative vertical (MEB) shifts (with respect to the origin) of field-cooled hysteresis curves are observed. Interestingly, both magnetization and EB (HEB and MEB) become zero at TCOMP. In addition, the EB (HEB and MEB) effect is maximum for a cooling field of 5 kOe, which is also the maximum field for observing NM behavior in La0.5Pr0.5CrO3, indicating a correlation between EB and NM. Rietveld refined neutron diffraction patterns at various temperatures infer a Gy type AFM ordering of Cr3+ moments below TN. Both NM and positive EB phenomena have been explained by considering the AFM exchange interaction between an induced moment of Pr3+ and a FM component of canted Cr3+ moment. The understanding is significant as it may open up the possibility for making thermomagnetic switches, magnetic memory, and other spintronic devices.
Material informatics for layered high-T
C superconductors
Authors: Liu Zhong-Li , Kang Peng , Zhu Yu , Liu Lei , Guo Hong
Published: June 2020

Superconductors were typically discovered by trial-and-error aided by the knowledge and intuition of individual researchers. In this work, using materials informatics aided by machine learning (ML), we build an ML model of superconductors, which is based on several material descriptors with apparent physical meanings to efficiently predict critical superconducting temperature TC. The descriptors include the average atomic mass of a compound, the average number of electrons in an unfilled shell, the average ground state atomic magnetic moments, the maximum difference of electronegativity, etc. To fully optimize the ML model, we develop a multi-step learning and multi-algorithm cross-verification approach. For known high TC superconductors, our ML model predicts excellent TC values with over 92% confidence. When the ML model is applied to about 2500 layered materials in the inorganic crystal structure database, 25 of them are predicted to be superconductors not known before, including 12 cuprates, 7 iron-based crystals, and 6 others, with TC ranging from ∼32 K to ∼138 K. The findings shed considerable light on the mapping between the material descriptors and TC for layered superconductors. The ML calculates that in our descriptors, the maximum difference of electronegativity is the most important one.
Laser-induced magnetization dynamics in a van der Waals ferromagnetic Cr2Ge2Te6 nanoflake
Authors: Zhang Tongyao , Chen Yuansen , Li Yanxu , Guo Zhichao , Wang Zhi , Han Zheng , He Wei , Zhang Jing
Published: June 2020

Laser-induced magnetization dynamics is quantitatively investigated in a van der Waals ferromagnetic Cr2Ge2Te6 nanoflake by means of time-resolved Faraday rotation. Under ferromagnetic resonance conditions, the angular dependence of spin precession dynamics gives rise to a perpendicular magnetic anisotropy with an effective field of 125 ± 8 mT. We further determine the field dependence of the effective damping coefficient, which is dominated by the inhomogeneous broadening of magnetic anisotropy in the regime of a small magnetic field while it diminishes to an intrinsic value of 0.006 ± 0.002 at high fields.
Thermal convection studies in liquid metal flow inside a horizontal duct under the influence of transverse magnetic field
Authors: Sahu S. , Courtessole C. , Ranjan A. , Bhattacharyay R. , Sketchley T. , Smolentsev S.
Published: June 2020

An experiment is conducted to study the effect of magnetic field on heat transfer in a magnetohydrodynamic flow of molten lead–lithium, in a stainless steel thin-wall duct, with a uniform surface heat flux at its bottom wall. A novel technique of measuring fluid temperature inside the duct is applied to map the temperature profile in a flow cross section, at both ends of the heated section, using a 4 × 4 array of 16 equidistantly placed thermocouples. Surface temperature, as well as electric potential, is measured at seven different locations along the heated section. Based on the temperature profiles obtained at the outlet of the heated section, various flow regimes have been identified over the experimentally investigated flow parameters. Distinctively, three flow regimes have been recognized depending on the dominance of buoyancy force, electromagnetic force, and inertial force. In order to better understand the experimental data, numerical simulations are performed using COMSOL. In the buoyancy force dominated flow regime, a quasi-two-dimensional turbulence flow is predominant, determining the overall heat transfer mechanism. In the electromagnetic force dominated regime, the perturbation due to buoyancy force is suppressed by the magnetic field. Finally, in the inertial force dominated regime, the electromagnetic force and buoyancy force do not play a significant role in determining the heat transfer mechanism. The transition between observed flow regimes has been identified in terms of Grashof, Reynolds, and Hartmann numbers, and the Nusselt number has been calculated for quantitative comparison of heat transfer in these flow regimes.
Detecting causality from time series in a machine learning framework
Authors: Huang Yu , Fu Zuntao , Franzke Christian L. E.
Published: June 2020

Detecting causality from observational data is a challenging problem. Here, we propose a machine learning based causality approach, Reservoir Computing Causality (RCC), in order to systematically identify causal relationships between variables. We demonstrate that RCC is able to identify the causal direction, coupling delay, and causal chain relations from time series. Compared to a well-known phase space reconstruction based causality method, Extended Convergent Cross Mapping, RCC does not require the estimation of the embedding dimension and delay time. Moreover, RCC has three additional advantages: (i) robustness to noisy time series; (ii) computational efficiency; and (iii) seamless causal inference from high-dimensional data. We also illustrate the power of RCC in identifying remote causal interactions of high-dimensional systems and demonstrate its usability on a real-world example using atmospheric circulation data. Our results suggest that RCC can accurately detect causal relationships in complex systems.
The collaborative and selective nature of interpreting in police interviews with stand-by interpreting
Authors: Monteoliva-García Eloísa
Published: June 2020

This study explores interaction in two authentic interpreter-mediated police interviews with suspects. The
analysis focuses on the interpreting regime used: stand-by interpreting. The interactional regime in the analysed interviews
featured exolingual communication in English between a Spanish-speaking suspect with emerging competencies in English and
English-speaking interviewers, with intermittent interpreter participation. Drawing on Conversation Analysis and interactional
sociolinguistics, this study analyses how the interpreting regime was negotiated, how it was constructed over the course of the
interviews, and the observable function of interpreting episodes. The analysis revealed a markedly collaborative nature of
stand-by interpreting, differences in the distribution of interactional power over interpreting episodes among the three
participants depending on their activity role and the interview phase, and the multimodal nature of turn-management. Interpreting
was used selectively as a resource to either repair or prevent miscommunication, aligning with the way the interpreting regime was
set up. Rather than advocating for or against the stand-by mode of interpreting, this paper describes its features in the police
interview and highlights both its potential and its risks for communication in interpreter-mediated police interviews as a
discourse genre.
L2 Spanish clitic pronouns
Authors: Peace Meghann M.
Published: June 2020

Spanish clitic pronouns present multiple morphosyntactic and semantic challenges to second language learners. One
particular issue is that of case marking, which can be further complicated by variable native input. As a result, a number of factors have
been proposed to explain L2 clitics, such as acquisition sequences, classroom input, dialect-specific input, and animacy cues (e.g. Andersen, 1984; Geeslin, García-Amaya, Hasler-Barker, Henriksen,
& Killam, 2010; Malovrh, 2008; Malovrh &
Lee, 2013; VanPatten, 1990; Zyzik, 2004).
This paper uses the Dynamic Systems Theory to describe and explain L2 Spanish clitic development. The multiple social and linguistic
variables that interact in clitic production suggest that clitics constitute a dynamic system. The data presented here come from a
cross-sectional analysis of four groups of university-level L1 English learners of L2 Spanish, as well as a group of native Spanish
speakers, who produced semi-spontaneous narration as well as post-production stimulated recall and interview. The results show a progression
that is not always linear in terms of certain levels, learners, and measures. The quantitative and qualitative results reveal various
interrelated social, linguistic, and cognitive factors which all play a role in the dynamic system of clitic case development.
Triangular lattice models for pattern formation by core–shell particles with different shell thicknesses
Authors: Grishina V S , Vikhrenko V S , Ciach A
Published: June 2020

Triangular lattice models for pattern formation by hard-core soft-shell particles at interfaces are introduced and studied in order to determine the effect of the shell thickness and structure. In model I, we consider particles with hard-cores covered by shells of cross-linked polymeric chains. In model II, such inner shell is covered by a much softer outer shell. In both models, the hard cores can occupy sites of the triangular lattice, and nearest-neighbor repulsion following from overlapping shells is assumed. The capillary force is represented by the second or the fifth neighbor attraction in model I or II, respectively. Ground states with fixed chemical potential μ or with fixed fraction of occupied sites c are thoroughly studied. For T > 0, the μ(c) isotherms, compressibility and specific heat are calculated by Monte Carlo simulations. In model II, 6 ordered periodic patterns occur in addition to 4 phases found in model I. These additional phases, however, are stable only at the phase coexistence lines at the (μ, T) diagram, which otherwise looks like the diagram of model I. In the canonical ensemble, these 6 phases and interfaces between them appear in model II for large intervals of c and the number of possible patterns is much larger than in model I. We calculated line tensions for different interfaces, and found that the favorable orientation of the interface corresponds to its smoothest shape in both models.
Coherent control for qubit state readout
Authors: Roman Conrad , Ransford Anthony , Ip Michael , Campbell Wesley C
Published: June 2020

Short pulses from mode-locked lasers can produce background-free atomic fluorescence by allowing temporal separation of the prompt incidental scatter from the subsequent atomic emission. We use this to improve our quantum state detection of optical-frequency and electron-shelved trapped ion qubits by more than two orders of magnitude. For direct detection of qubits defined on atomic hyperfine structure, however, the large bandwidth of short pulses is greater than the hyperfine splitting, and repeated excitation is not qubit state selective. Here, we show that the state resolution needed for projective quantum measurement of hyperfine qubits can be recovered by applying techniques from coherent control to the orbiting valence electron of the queried ion. We demonstrate electron wavepacket interference to allow readout of the original qubit state using broadband pulses, even in the presence of large amounts of background laser scatter.
Influence of Tumor Number on Clinicopathologic Features and Outcomes of Patients With Papillary Thyroid Carcinoma
Authors: Feng Jia-Wei , Wu Wan-Xiao , Hu Jun , Hong Li-Zhao , Qin An-Cheng , Jiang Yong , Ye Jing
Published: June 2020

Objectives

The purpose of this study was to investigate the significance of tumor number on clinicopathologic factors and outcomes of patients with papillary thyroid carcinoma (PTC).

Methods

We retrospectively analyzed 667 patients with PTC. We compared clinicopathologic features of patients with a different tumor number. Cox proportional hazards model was used to analyze risk factors of recurrence.

Results

In papillary thyroid microcarcinoma (PTMC), the increase in the number of tumor foci was related to a higher risk of minimal extrathyroidal extension (ETE) and lymphovascular invasion (P < .05). Patients with PTMC with four or more foci had a significantly higher risk of central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) than patients with solitary tumors (P < .05). Patients with macro-PTC with four or more foci and with three foci had a higher risk of gross ETE and lymphovascular invasion than patients with solitary tumors (P < .05). The increase in the tumor number was related to a higher risk of CLNM in macro-PTC (P < .05). The number of foci was the independent predictor of recurrence in patients with macro-PTC (P < .05).

Conclusions

An increase in the number of tumors was associated with an increased risk of aggressive clinicopathologic features in PTMC and macro-PTC. The number of tumor foci could influence risk of recurrence in macro-PTC.
GLIDE: combining local methods and diffusion state embeddings to predict missing interactions in biological networks
Authors: Devkota Kapil , Murphy James M , Cowen Lenore J
Published: June 2020

Motivation

One of the core problems in the analysis of biological networks is the link prediction problem. In particular, existing interactions networks are noisy and incomplete snapshots of the true network, with many true links missing because those interactions have not yet been experimentally observed. Methods to predict missing links have been more extensively studied for social than for biological networks; it was recently argued that there is some special structure in protein–protein interaction (PPI) network data that might mean that alternate methods may outperform the best methods for social networks. Based on a generalization of the diffusion state distance, we design a new embedding-based link prediction method called global and local integrated diffusion embedding (GLIDE). GLIDE is designed to effectively capture global network structure, combined with alternative network type-specific customized measures that capture local network structure. We test GLIDE on a collection of three recently curated human biological networks derived from the 2016 DREAM disease module identification challenge as well as a classical version of the yeast PPI network in rigorous cross validation experiments.

Results

We indeed find that different local network structure is dominant in different types of biological networks. We find that the simple local network measures are dominant in the highly connected network core between hub genes, but that GLIDE’s global embedding measure adds value in the rest of the network. For example, we make GLIDE-based link predictions from genes known to be involved in Crohn’s disease, to genes that are not known to have an association, and make some new predictions, finding support in other network data and the literature.

Availability and implementation

GLIDE can be downloaded at https://bitbucket.org/kap_devkota/glide.

Supplementary information

Supplementary data are available at Bioinformatics online.
A new classification ofCarex(Cyperaceae) subgenera supported by a HybSeq backbone phylogenetic tree
Authors: Villaverde Tamara , Jiménez-Mejías Pedro , Luceño Modesto , Waterway Marcia J , Kim Sangtae , Lee Bora , Rincón-Barrado Mario , Hahn Marlene , Maguilla Enrique , Roalson Eric H , Hipp Andrew L ,   THE GLOBAL CAREX GROUP, Wilson K L , Larridon I , Gebauer S , Hoffmann M H , Simpson D A , Naczi R F C , Reznicek A A , Ford B A , Starr J R , Park J , Escudero M , Martín-Bravo S
Published: June 2020

The field of systematics is experiencing a new molecular revolution driven by the increased availability of high-throughput sequencing technologies. As these techniques become more affordable, the increased genomic resources have increasingly far-reaching implications for our understanding of the Tree of Life. With c. 2000 species, Carex (Cyperaceae) is one of the five largest genera of angiosperms and one of the two largest among monocots, but the phylogenetic relationships between the main lineages are still poorly understood. We designed a Cyperaceae-specific HybSeq bait kit using transcriptomic data of Carex siderosticta and Cyperus papyrus. We identified 554 low-copy nuclear orthologous loci, targeting a total length of c. 1 Mbp. Our Cyperaceae-specific kit shared loci with a recently published angiosperm-specific Anchored Hybrid Enrichment kit, which enabled us to include and compile data from different sources. We used our Cyperaceae kit to sequence 88 Carex spp., including samples of all the five major clades in the genus. For the first time, we present a phylogenetic tree of Carex based on hundreds of loci (308 nuclear exon matrices, 543 nuclear intron matrices and 66 plastid exon matrices), demonstrating that there are six strongly supported main lineages in Carex: the Siderostictae, Schoenoxiphium, Unispicate, Uncinia, Vignea and Core Carex clades. Based on our results, we suggest a revised subgeneric treatment and provide lists of the species belonging to each of the subgenera. Our results will inform future biogeographic, taxonomic, molecular dating and evolutionary studies in Carex and provide the step towards a revised classification that seems likely to stand the test of time.
Risk of Viral Infection in Patients Using Either Angiotensin-converting Enzyme Inhibitors or Angiotensin Receptor Blockers: A Nationwide Population-based Propensity Score Matching Study
Authors: Lin Shih-Yi , Ju Shu-Woei , Lin Cheng-Li , Lin Cheng-Chieh , Hsu Wu-Huei , Chou Chia-Hui , Chi Chih-Yu , Hsu Chung-Y , Kao Chia-Hung
Published: June 2020

Background

We hypothesized that renin–angiotensin system (RAS) blockers have systemic protective effects beyond the respiratory tract and could reduce the risk of viral infections.

Methods

We used the National Health Insurance Research Database and identified 2 study cohorts: the angiotensin receptor blocker (ARB) cohort and angiotensin-converting enzyme inhibitor (ACEI) cohort. Propensity score matching was applied at a 1:1 ratio by all associated variables to select 2 independent control cohorts for the ARB and ACEI cohorts. A Cox proportional hazards model was applied to assess the end outcome of viral infection.

Results

The number of ARB and ACEI users was 20 207 and 18 029, respectively. The median age of ARB users and nonusers was 53.7 and 53.8 years, respectively. The median follow-up duration of ARB users and nonusers was 7.96 and 7.08 years; the median follow-up duration of ACEI users and nonusers was 8.70 and 8.98 years, respectively. The incidence rates of viral infections in ARB users and nonusers were 4.95 and 8.59 per 1000 person-years, respectively, and ARB users had a lower risk of viral infection than nonusers (adjusted hazard ratio [aHR], 0.53 [95% confidence interval {CI}, .48–.58]). The incidence rates of viral infections in ACEI users and nonusers were 6.10 per 1000 person-years and 7.72 per 1000 person-years, respectively, and ACEI users had a lower risk of viral infection than nonusers (aHR, 0.81 [95% CI, .74–.88]).

Conclusions

Hypertensive patients using either ARBs or ACEIs exhibit a lower risk of viral infection than nonusers.
A Machine Learning Approach for the Automated Interpretation of Plasma Amino Acid Profiles
Authors: Wilkes Edmund H , Emmett Erin , Beltran Luisa , Woodward Gary M , Carling Rachel S
Published: June 2020

BACKGROUND

Plasma amino acid (PAA) profiles are used in routine clinical practice for the diagnosis and monitoring of inherited disorders of amino acid metabolism, organic acidemias, and urea cycle defects. Interpretation of PAA profiles is complex and requires substantial training and expertise to perform. Given previous demonstrations of the ability of machine learning (ML) algorithms to interpret complex clinical biochemistry data, we sought to determine if ML-derived classifiers could interpret PAA profiles with high predictive performance.

METHODS

We collected PAA profiling data routinely performed within a clinical biochemistry laboratory (2084 profiles) and developed decision support classifiers with several ML algorithms. We tested the generalization performance of each classifier using a nested cross-validation (CV) procedure and examined the effect of various subsampling, feature selection, and ensemble learning strategies.

RESULTS

The classifiers demonstrated excellent predictive performance, with the 3 ML algorithms tested producing comparable results. The best-performing ensemble binary classifier achieved a mean precision-recall (PR) AUC of 0.957 (95% CI 0.952, 0.962) and the best-performing ensemble multiclass classifier achieved a mean F4 score of 0.788 (0.773, 0.803).

CONCLUSIONS

This work builds upon previous demonstrations of the utility of ML-derived decision support tools in clinical biochemistry laboratories. Our findings suggest that, pending additional validation studies, such tools could potentially be used in routine clinical practice to streamline and aid the interpretation of PAA profiles. This would be particularly useful in laboratories with limited resources and large workloads. We provide the necessary code for other laboratories to develop their own decision support tools.
Family Planning and Development: Aggregate Effects of Contraceptive Use
Authors: Cavalcanti Tiago , Kocharkov Georgi , Santos Cezar
Published: June 2020

What is the role of family planning interventions on fertility, savings, human capital investment and development? To examine this, endogenous unwanted fertility is embedded in an otherwise standard quantity–quality overlapping generations model of fertility and growth. The model features costly fertility control and families can (partially) insure against a fertility risk by using costly modern contraceptives. In the event of unexpected pregnancies, households can also opt to abort some pregnancies, at a cost. Given the number of children born, parents decide how much education to provide and how much to save out of their income. We fit the model to Kenyan data, implement several family planning policies and decompose their aggregate effects. Our results suggest that with a small government budget (say, up to 0.5% of GDP), family planning interventions might be more cost-effective in improving long-run living standards than policies that subsidise basic education.
Cardiac arrest at rest and during sport activity: causes and prevention
Authors: Basso Cristina , Rizzo Stefania , Carturan Elisa , Pilichou Kalliopi , Thiene Gaetano
Published: June 2020

In the Western Countries, cardiovascular diseases are still the most frequent cause of death, which is often sudden. Sudden death (SD) in the young population occurs at a rate of 1/100 000/year and carries a profound social impact both for the young age of the victims and the unanticipated occurrence. Physical effort is a triggering risk factor, in fact SD occurs three times more frequently in athletes than in non-athletes. The screening for sport activity fitness can identify apparently healthy subjects carrying a silent abnormality able to trigger sudden cardiac death during sport activity, thus the fitness screening could be lifesaving. The spectrum of cardiovascular conditions identified at post-mortem examination is quite extensive, and include: coronary, myocardial, valvular diseases, as well as conduction system abnormalities. In 20% of the cases, the heart is normal, and sudden cardiac death is ascribed to ionic channel disease. The diagnosis of cardiomyopathy is possible with the integration of electrocardiogram and echography, thus decreasing significantly the occurrence of SD of athletes in Italy, but early diagnosis of coronary artery disease still remains challenging. The best strategy to further decrease sudden cardiac death during sport activities consists in combining early diagnosis with widespread availability of defibrillators on site.
The argument of the ORBITA study: angioplasty is useless
Authors: Bolognese Leonardo
Published: June 2020

The goal of treatment in stable coronary artery disease is to improve prognosis and quality of life of the patients. International Guidelines support revascularization procedures for symptomatic patients unresponsive to optimal medical treatment. Previous studies demonstrated, in fact, the therapeutic efficacy of coronary angioplasty in reducing angina and improving the functional capacity of these patients. The ORBITA study, recently published, challenged these assertions by demonstrating the lack of benefit of angioplasty over placebo in terms of effort tolerance in a population of patients with single-vessel coronary artery disease. What lesson could we learn from the ORBITA study?
Treatment of stable ischaemic heart disease: the old and the new
Authors: Santucci Andrea , Riccini Clara , Cavallini Claudio
Published: June 2020

Stable ischaemic heart disease is a frequent and very heterogeneous condition. Drug therapy is important, in these patients, for improving their prognosis and controlling their symptoms. The typical clinical manifestation of obstructive coronary disease is angina pectoris. This symptom can be improved by various classes of compounds, namely beta-blockers (BBs), calcium antagonist, and nitrates. More recently, ranolazine and ivabradine have been introduced. All these drugs have been proven to reduce significantly angina. On the other hand, there are no evidences supporting improvement in prognosis, besides for the use of BBs, in patients with previous myocardial infarction (MI) or systolic dysfunction. Besides drugs for symptoms control, these patients also receive antiplatelet drugs, specifically aspirin, and lipid lowering compounds such as statins. Furthermore, recent evidences supported the use of low doses direct anticoagulant, or a second antiplatelet agent in patients with previous MI. Similarly, a very low LDL cholesterol level, such as obtained with PCKS9 inhibitors, seems very beneficial in these patients. It is possible that in the near future a specific role for neo-angiogenesis factors and cellular therapies, could be proven, albeit, presently these treatments are not supported by solid evidences.
Transcatheter aortic valve implantation in Italy: an uneven growth
Authors: Masiero Giulia , Musumeci Giuseppe
Published: June 2020

Transcatheter aortic valve implantation (TAVI) is the treatment of choice in patients with severe symptomatic aortic stenosis who are not suitable for surgery. The procedure has become the preferred strategy in patients at intermediate/high surgical risk with favourable clinical and anatomical characteristics. The collected scientific evidences, as well as the technologic innovations shaping the newer devices, allowed for a progressive reduction of the procedure-related complications as a well as a simplification of the procedure itself, promoting the gradual expansion of the indication for TAVI with the consequent increase in the estimated number of procedures performed each year. There are significant geographic and socio-economic disparities in the use of TAVI around the world and in Italy as well, reflecting an application of the procedure directly related to the economic prosperity of the Health System of the Country examined. The Italian situation, similar to the worldwide reality, reveals an uneven application of the procedure, signalling a disparity in the socio-economic and organizational capabilities of each single region. Standardization of patient selection for treatment, and of the clinical pathway for TAVI are crucial for an homogeneous integration of this new technology in the current Health Care System.
Preventing myocardial infarction: use and limitation of non-invasive imaging modalities
Authors: Perna Gian Piero
Published: June 2020

Identifying patients at high risk of coronary events is the main focus of cardiovascular prevention. For primary prevention score and risk cards are very low cost solutions, but only of limited efficacy, thus justifying the use of non-invasive imaging testing for the purpose of increasing the ‘diagnostic gain’. Considering all the diagnostic tests employed, only few demonstrated significant additional contribution to the risk score stratification. Coronary imaging with high speed volumetric computed tomography can provide essential information in ruling out and/or definition of coronary artery disease but also has limitations as far as the biological risk, the costs, and the difficulties of putting into perspective the results obtained in asymptomatic patients.
Coronary inflammation: why searching, how to identify and treat it
Authors: Prati Francesco , Marco Valeria , Paoletti Giulia , Albertucci Mario
Published: June 2020

Inflammation plays an important role in the development of atherosclerotic lesions. A variety of stimuli promote atherosclerosis, including increased LDL cholesterol in blood, exposure to tobacco, diabetes mellitus, hypertension, or rheological stress. Inflammatory cells have an established role in the growth of atherosclerotic lesions. Macrophages recognize and internalise ox-LDL to eventually become lipid-laden foam cells, the hallmark cellular component of atheroma. Infiltrating CD4-T cells have a role too, by interacting with ox-LDL and other antigens. Cytokines secreted by inflammatory cells stimulate smooth muscle cells migration whilst macrophages produce metalloprotease that lead to fibrous cap rupture. The necrotic debris of died macrophages and smooth muscle cells help to continue the inflammatory process. The inflammatory response can also directly activate platelets and promote thrombus formation at the surface of complicated coronary plaques. The CANTOS trial can be waived as an innovative study promoting a novel approach of personalized medicine. In patients with previous myocardial infarction, high-sensitivity C-reactive protein level of 2 mg and normal LDL level (<70 mg/dL), canakinumab a therapeutic monoclonal antibody targeting interleukin-1β, at a dose of 150 mg every 3 months, led to a significant reduction of the primary efficacy end point: nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death at 48 months. Based on the CANTOS results, patients on statins and residual inflammatory risk as assessed by means of a high-sensitivity CRP >2 mg/l at baseline have a high risk of future cardiac events, comparable to that of statin-treated patients with suboptimal cholesterol LDL level. The inhibition of interleukin-1β by means of canakinumab, which is only one of many potential anti-inflammatory pathways, open new perspectives, showing that a selective inhibition of the inflammatory pathway may be beneficial in reducing cardiovascular risk. In a process of personalized medicine, there is need to accurately identify patients at high risk of events, to be treated with potent statins or anti-inflammatory drugs. Perhaps in the near future a more specific assessment of coronary inflammations, possibly obtained with imaging modalities (either invasive or non-invasive), will better select patients at risk of events. In this scenario, in the setting of secondary prevention, OCT may serve the scope of identifying vulnerable plaques with local aggregates of inflammatory cells. Future studies are needed to understand the clinical effectiveness of strategies based on invasive coronary assessment.
Prevention after acute coronary syndrome the ‘less is more’ philosophy
Authors: Temporelli Pier Luigi
Published: June 2020

In the cardiology field, in recent years, we have witnessed an exponential increase in the use of both invasive and non-invasive instrument diagnostics. Particularly after an acute coronary syndrome, instrumental examinations, especially non-invasive ones, are often prescribed inappropriately until they almost completely replace the clinical evaluation. Their correct use, on the contrary, would require the choice of a test to be prescribed according to the epidemiological and clinical context of the individual patient. The strategy of early diagnosis, obtainable through instrumental screening and borrowed from oncological pathologies, was transferred ‘tout court’ in the cardiovascular field without any scientific basis, replacing the pharmacological or non-pharmacological intervention, such as the appropriate lifestyle, aimed at reducing cardiovascular risk factors. The guidelines of the main scientific societies define the most appropriate paths in the management of the coronary heart disease patients, both in the immediate post-acute phase and in the chronic phase. Although the guidelines sometimes show an excessive simplification of clinical problems, in an age in which the control of health expenditure has become a priority the correctness of the indications is an indispensable objective, being incontrovertible that a test is indicated only when an instrumental examination is able to modify the diagnostic-therapeutic path and the outcome of the patient.
Antiplatelet therapy and coronary artery bypass grafting: a systematic review and network meta-analysis
Authors: Gupta Saurabh , Belley-Cote Emilie P , Panchal Puru , Pandey Arjun , Basha Ameen , Pallo Lindsay , Rochwerg Bram , Mehta Shamir , Schwalm J -D , Whitlock Richard P
Published: June 2020

OBJECTIVES

Acetylsalicylic acid (ASA) monotherapy is the standard of care after coronary artery bypass grafting (CABG), but the benefits of more intense antiplatelet therapy, specifically dual antiplatelet therapy (DAPT), require further exploration in CABG patients. We performed a network meta-analysis to compare the effects of various antiplatelet regimens on saphenous vein graft patency, mortality, major adverse cardiovascular events and bleeding among CABG patients.

METHODS

We searched Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval Systems Online, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, American College of Physicians Journal Club and conference proceedings for randomized controlled trials. Screening, data extraction, risk of bias assessment and Grading of Recommendations Assessment, Development and Evaluation were performed in duplicate. We conducted a random effect Bayesian network meta-analysis including both direct and indirect comparisons.

RESULTS

We included 43 randomized controlled trials studying 15 511 patients. DAPT with low-dose ASA and ticagrelor [odds ratio (OR) 2.53, 95% credible interval (CrI) 1.35–4.72; I2 = 55; low certainty] or clopidogrel (OR 1.56, 95% CrI 1.02–2.39; I2 = 55; very low certainty) improved saphenous vein graft patency when compared to low-dose ASA monotherapy. DAPT with low-dose ASA and ticagrelor was associated with lower mortality (OR 0.52, 95% CrI 0.30–0.87; I2 = 14; high certainty) and lower major adverse cardiovascular events (OR 0.63, 95% CrI 0.44–0.91; I2 = 0; high certainty) when compared to low-dose ASA monotherapy. Based on moderate certainty evidence, DAPT was associated with an increase in major bleeding.

CONCLUSIONS

Our results suggest that DAPT improves saphenous vein graft patency, mortality and major adverse cardiovascular event. As such, surgeons and physicians should consider re-initiating DAPT for acute coronary syndrome patients after their CABG, at the expense of an increased risk for major bleeding.

Clinical trial registration

International Prospective Register of Systematic Reviews ID Number CRD42019127695
Elevated CXCL10 Serum Levels in Measles Virus Primary Infection and Reinfection Correlate With the Serological Stage and Hospitalization Status
Authors: Semmler Georg , Griebler Hannah , Aberle Stephan W , Stiasny Karin , Richter Lukas , Holzmann Heidemarie , Weseslindtner Lukas
Published: June 2020

We quantified serum concentrations of chemokine CXCL10 in 288 patients with measles virus (MeV) primary infection and 16 patients with reinfection (vaccine failure). CXCL10 peaked with emergence of IgM antibodies and was elevated in hospitalized patients (3233 vs 1930 pg/mL, P < .0001). CXCL10 differed between primary and reinfection (1958 vs 932 pg/mL, P = .0402). In comparison to other viral infections with rash-like symptoms, CXCL10 was highly elevated in MeV infection (area under the curve = 0.935; 95% confidence interval, .905–.965; P < .0001). CXCL10 is a potential marker for diagnosis, stage, and severity of MeV infection.