bluuebunny/crossref_metadata_2025 huggingface dataset:
The revised International Code of Medical Ethics: an exercise in international professional ethical self-regulation
Authors: Parsa-Parsi Ramin W , Gillon Raanan , Wiesing Urban
Published: July 2023

The World Medical Association (WMA), the global representation of the medical profession, first adopted the International Code of Medical Ethics (ICoME) in 1949 to outline the professional duties of physicians to patients, other physicians and health professionals, themselves and society as a whole. The ICoME recently underwent a major 4-year revision process, culminating in its unanimous adoption by the WMA General Assembly in October 2022 in Berlin. This article describes and discusses the ICoME, its revision process, the controversial and uncontroversial issues, and the broad consensus achieved among WMA constituent members, representing over 10 million physicians worldwide. The authors analyse the ICoME, including its response to contemporary changes and challenges like ethical plurality and globalisation, in light of ethical theories and approaches, reaching the conclusion that the document is a good example of international ethical professional self-regulation.
Microenvironment has little effect on the litter decomposition rate of temperate trees
Authors: Piper Frida I. , Cárdenas Alejandro , Zúñiga-Feest Alejandra , Orlando Julieta , Leiva Diego , Rolleri Aldo
Published: July 2023

Individual tree species might affect underground soil properties to favor the decomposition of their own litter. However, in some studies, monospecific litter decomposed faster underneath multispecific canopies than under canopies of the same species as the litter, suggesting that plant diversity in the overstorey creates a more favorable decomposition microenvironment. We compared the decomposition rate of monospecific litter from eight temperate tree species under the crown of the same species as the litter (conspecific canopy), and a multispecific canopy formed by eight species. Using model selection, we determined the influence of the microenvironments, species, and litter chemistry on decomposition rates. The most robust model included the species and canopy type, but it differed only slightly from the model including only the species. Decomposition rates were significantly different among species and higher in conspecific canopy than multispecific canopy in all species. Models including specific leaf area and different combinations of chemical traits of the litter were less robust than the null model. These results show that the species origin of the litter was significantly more important than the microenvironment to explain litter decomposition rates.
Investigation of anomalous triple gauge couplings in μγ collision at multi-TeV muon colliders
Authors: Spor Serdar , Köksal Murat
Published: July 2023

The pursuit of discovery in particle physics has always required study at the highest possible energies. Multi-TeV muon colliders, which have important advantages, offer unprecedented potential for investigating new physics beyond the Standard Model. We extensively assume a range of center-of-mass energies from 3 to 30 TeV and a range of integrated luminosities from 1 to 90 ab−1 for future multi-TeV muon colliders. We perform a phenomenological study of the anomalous WWγ couplings via the process [Formula: see text] using a model-independent analysis in the effective field theory framework at multi-TeV muon colliders. The sensitivity estimates obtained for the anomalous WWγ couplings at systematic uncertainties of δsys = 0%, 3%, 5% are compared with the experimental results. Our best sensitivity limits at 95% confidence level for cWWW/Λ2, [Formula: see text], c B /Λ2, c W /Λ2, and [Formula: see text] couplings are [−0.030; 0.025], [−0.014; 0.014], [−0.185; 0.187], [−0.187; 0.189], and [−1.177; 1.097] TeV−2 at the multi-TeV muon collider with center-of-mass energy of 30 TeV and integrated luminosity of 90 ab−1, respectively.
Laser-assisted electron–nucleon scattering
Authors: Dahiri I. , Baouahi M. , Ouali M. , Manaut B. , El Idrissi M. , Taj S.
Published: July 2023

In the absence and presence of a circularly polarized monochromatic electromagnetic pulse, we have analyzed the electron–nucleon scattering process, where the nucleon is assumed to be spinless with a spherical shape. We have provided the theoretical calculation of the differential cross section (DCS) by using the Dirac–Volkov formalism. This research paper aims to provide two comparisons: We first compare the DCS in the absence of the laser field with its corresponding laser-assisted DCS. A second comparison is made between the electron–proton and electron–neutron scattering processes to study the effect of the laser on both processes. The results obtained about the effect of the laser field on the DCS and the electric form factor have been discussed for both scattering processes. We have found that the DCS is reduced when the laser field is applied for both processes. In addition, the form factor is also decreased by raising the incident electron energy in electron–proton scattering, but it increases in electron–neutron scattering. Moreover, the form factors for both scattering situations are unchanged by raising the laser field strength up to [Formula: see text].
A novel mathematical model of MHD boundary layer flow of an activated micropolar nanofluid over a stretching surface under the effect of electro-osmosis forces
Authors: Eldabe Nabil T. , Hussein Sameh A. , Gabr Mahmoud E. , Zaher Abdullah Z.
Published: July 2023

The major objective of this research is to create a novel mathematical model for the flow of an electro-osmotic boundary layer in a micropolar Williamson nanofluid. This development is achieved by considering the influence of electro-osmotic force on an incompressible micropolar Williamson nanofluid through a Darcian flow (Darcy model) when combined with a binary chemical reaction and the energy of activation over a linearly stretching sheet. The constituent parts of the energy equation include heat radiation, thermal and mass transport, along with joule-based heating and dissipation of viscous fluids. The problem is computationally analyzed using an equation set of nonlinear partial differential equations (PDEs), which are then similarly converted into a system of ordinary differentiation equations (ODEs). The obtained ODEs system is solved numerically using the built-in command (Parametric ND Solve) via MATHEMATICA software. A series of figures are used to demonstrate numerically and graphically the influence of physical characteristics on the fluid behavior. The behavior of flow is obtained by studying the streamlines around the plate in contour and three-dimensional form. In the case of non-Newtonian fluid, the results indicated that the boundary layer velocity is slower compared with the Newtonian fluid case. It is also mentioned that the graphic representation of the results shows that increasing the radiation parameter enhances thermal distribution, which means that the rate of heat transfer improved. The main findings revealed that the upward trend in the Williamson number diminishes the nanofluid flow while enhancing the skin friction coefficient. Also, it is discovered that as [Formula: see text] rises, the fluid’s velocity distributions in the boundary layer rise. Consequently, this type of research’s significance stems from its potential uses in biomedical engineering since it could be used to dewater liquids and solids from infected human tissues.
Fine_Denseiganet: Automatic Medical Image Classification in Chest CT Scan Using Hybrid Deep Learning Framework
Authors: Sahu Hemlata P. , Kashyap Ramgopal
Published: July 2023

Medical image classification is one of the most significant tasks in computer-aided diagnosis. In the era of modern healthcare, the progress of digitalized medical images has led to a crucial role in analyzing medical image analysis. Recently, accurate disease recognition from medical Computed Tomography (CT) images remains a challenging scenario which is important in rendering effective treatment to patients. The infectious COVID-19 disease is highly contagious and leads to a rapid increase in infected individuals. Some drawbacks noticed with RT-PCR kits are high false negative rate (FNR) and a shortage in the number of test kits. Hence, a Chest CT scan is introduced instead of RT-PCR which plays an important role in diagnosing and screening COVID-19 infections. However, manual examination of CT scans performed by radiologists can be time-consuming, and a manual review of each individual CT image may not be feasible in emergencies. Therefore, there is a need to perform automated COVID-19 detection with the advances in AI-based models. This work presents effective and automatic Deep Learning (DL)-based COVID-19 detection using Chest CT images. Initially, the data is gathered and pre-processed through Spatial Weighted Bilateral Filter (SWBF) to eradicate unwanted distortions. The extraction of deep features is processed using Fine_Dense Convolutional Network (Fine_DenseNet). For classification, the Softmax layer of Fine_DenseNet is replaced using Improved Generative Adversarial Network_Artificial Hummingbird (IGAN_AHb) model in order to train the data on the labeled and unlabeled dataset. The loss in the network model is optimized using Artificial Hummingbird (AHb) optimization algorithm. Here, the proposed DL model (Fine_DenseIGANet) is used to perform automated multi-class classification of COVID-19 using CT scan images and attained a superior classification accuracy of 95.73% over other DL models.
Anthropogenic influence on groundwater geochemistry in Horn Creek Watershed near the Orphan Mine in Grand Canyon National Park, Arizona, USA
Authors: Beisner Kimberly R. , Davidson Collin , Tillman Fred
Published: July 2023

Breccia pipe deposits of the Grand Canyon region contain ore grade copper and uranium. Horn Creek is located near the Orphan Mine mineralized breccia pipe deposit, and groundwater emerging from the bedrock in the headwaters of Horn Creek has the highest uranium concentrations in the region. Uranium decreases an order of magnitude between the groundwater at the top of the watershed and the groundwater emerging from the alluvial material lower in the watershed. Horn Creek water has low sulfur and uranium isotopic ratios which may suggest interaction with sulfide and uranium minerals found in mineralized breccia pipe deposits. Per- and polyfluoroalkyl substances were found in low concentrations in groundwater from the bedrock and may be related to mining process materials or other anthropogenic activities. PHREEQC modelling suggests that water that is elevated in uranium emerging from the bedrock in the upper watershed may mix with other groundwater and atmospheric precipitation infiltrated into the alluvial material in the lower watershed. Tritium is elevated in Horn Creek groundwaters, suggesting a component of modern water, some of which may have interacted with Orphan Mine workings. Additional studies could build on this understanding of chemistry changes in the waters of Horn Creek to provide more direct evidence of the contribution of water moving through the Orphan Mine.

Supplementary material:
Chemical data for this paper are available at
https://doi.org/10.5066/F7P55KJN
, PHREEQC geochemical simulations are available at
https://doi.org/10.5066/P9X17FKG
and groundwater chemistry from south of Grand Canyon, AZ is available at
https://doi.org/10.6084/m9.figshare.c.6747638

Thematic collection:
This article is part of the Geochemical processes related to mined, milled, or natural metal deposits collection available at:
https://www.lyellcollection.org/topic/collections/geochemical-processes-related-to-mined-milled-or-natural-metal-deposits
Origin of the Songpan–Garzê terrane, Tibetan Plateau: a perspective from the tectonic evolution of the Palaeo-Tethys Ocean
Authors: Dan Wei , Yu Zhi-Wei , Wang Qiang , Tang Gong-Jian , Zhang Xiu-Zheng , Wang Jun
Published: July 2023

The Songpan–Garzê terrane is the largest Triassic remnant flysch basin on Earth and formed as the Palaeo-Tethys Ocean closed during the final amalgamation of the Pangaea supercontinent. However, the origin of the Songpan–Garzê terrane is highly controversial. A synthesis of the tectonic evolution of the Palaeo-Tethys Ocean and its branches surrounding the Songpan–Garzê terrane is presented, which clarifies the nature and relationships among the many Palaeo-Tethys sutures. Provenance analyses suggest that branches of the Palaeo-Tethys near the Songpan–Garzê terrane closed before the Early Triassic. In contrast, the main Palaeo-Tethys Ocean (Longmu Co-Shuanghu) did not close until the beginning of the Late Triassic. This study argues against the Songpan–Garzê terrane being a remnant ocean basin, and proposes that it was a back-arc basin of the main Palaeo-Tethys Ocean. It initially underwent extension by the combined effects of the main Palaeo-Tethys Ocean subduction and the Emeishan mantle plume in the Late Permian, and subsequently developed into a back-arc basin in the Triassic, into which huge turbiditie units were deposited derived from all surrounding terranes and orogens. The final closure of the main Palaeo-Tethys Ocean in the beginning of the Late Triassic and subsequent continent–continent collision led to basin inversion in the Late Triassic.
A Fast Algorithm for Aperiodic Linear Stencil Computation using Fast Fourier Transforms
Authors: Ahmad Zafar , Chowdhury Rezaul , Das Rathish , Ganapathi Pramod , Gregory Aaron , Zhu Yimin
Published: July 2023

Stencil computations are widely used to simulate the change of state of physical systems across a multidimensional grid over multiple timesteps. The state-of-the-art techniques in this area fall into three groups: cache-aware tiled looping algorithms, cache-oblivious divide-and-conquer trapezoidal algorithms, and Krylov subspace methods.

In this article, we present two efficient parallel algorithms for performing linear stencil computations. Current direct solvers in this domain are computationally inefficient, and Krylov methods require manual labor and mathematical training. We solve these problems for linear stencils by using discrete Fourier transforms preconditioning on a Krylov method to achieve a direct solver that is both fast and general. Indeed, while all currently available algorithms for solving general linear stencils perform Θ(NT) work, whereNis the size of the spatial grid andTis the number of timesteps, our algorithms performo(NT) work.

To the best of our knowledge, we give the first algorithms that use fast Fourier transforms to compute final grid data by evolving the initial data for many timesteps at once. Our algorithms handle both periodic and aperiodic boundary conditions and achieve polynomially better performance bounds (i.e., computational complexity and parallel runtime) than all other existing solutions.

Initial experimental results show that implementations of our algorithms that evolve grids of roughly 107cells for around 105timesteps run orders of magnitude faster than state-of-the-art implementations for periodic stencil problems, and 1.3× to 8.5× faster for aperiodic stencil problems.

Code Repository:https://github.com/TEAlab/FFTStencils
A General Layout Pattern Clustering Using Geometric Matching-based Clip Relocation and Lower-bound Aided Optimization
Authors: He Xu , Wang Yao , Fu Zhiyong , Wang Yipei , Guo Yang
Published: July 2023

With the continuous shrinking of feature size, detection of lithography hotspots has been raised as one of the major concerns in Design-for-Manufacturability (DFM) of semiconductor processing. Hotspot detection, along with other DFM measures, trades off turnaround time for the yield of IC manufacturing, and thus a simplified but wide-ranging pattern definition is a key to the problem. Layout pattern clustering methods, which group geometrically similar layout clips into clusters, have been vastly proposed to identify layout patterns efficiently. To minimize the clustering number for subsequent DFM processing, in this article, we propose a geometric-matching-based clip relocation technique to increase the opportunity of pattern clustering. Particularly, we formulate the lower bound of the clustering number as a maximum-clique problem, and we have also proved that the clustering problem can be solved by the result of the maximum-clique very efficiently. Compared with the experimental results of the state-of-the-art approaches on ICCAD 2016 Contest benchmarks, the proposed method can achieve the optimal solutions for all benchmarks with very competitive runtime. To evaluate the scalability, the ICCAD 2016 Contest benchmarks are extended and evaluated. Moreover, experimental results on the extended benchmarks demonstrate that our method can reduce the cluster number by 16.59% on average, while the runtime is 74.11% faster on large-scale benchmarks compared with previous works.
DDNAS: Discretized Differentiable Neural Architecture Search for Text Classification
Authors: Chen Kuan-Chun , Li Cheng-Te , Lee Kuo-Jung
Published: July 2023

Neural Architecture Search (NAS) has shown promising capability in learning text representation. However, existing text-based NAS neither performs a learnable fusion of neural operations to optimize the architecture nor encodes the latent hierarchical categorization behind text input. This article presents a novel NAS method, Discretized Differentiable Neural Architecture Search (DDNAS), for text representation learning and classification. With the continuous relaxation of architecture representation, DDNAS can use gradient descent to optimize the search. We also propose a novel discretization layer via mutual information maximization, which is imposed on every search node to model the latent hierarchical categorization in text representation. Extensive experiments conducted on eight diverse real datasets exhibit that DDNAS can consistently outperform the state-of-the-art NAS methods. While DDNAS relies on only three basic operations, i.e., convolution, pooling, and none, to be the candidates of NAS building blocks, its promising performance is noticeable and extensible to obtain further improvement by adding more different operations.
Adenosine reuptake inhibition reduces diabetes-induced glomerular hyperfiltration via the adenosine A2a receptor
Authors: Persson Patrik , Fasching Angelica , Pihl Liselotte , Palm Fredrik
Published: July 2023

Diabetes-induced glomerular hyperfiltration is an early alteration in kidney function in diabetes. Previous studies have shown that reduced adenosine A2a receptor signaling contributes to diabetes-induced glomerular hyperfiltration. The present study investigated the effects of enhanced interstitial adenosine concentration by inhibition of cellular adenosine reuptake, thereby promoting endogenous adenosine signaling. Insulinopenic diabetes was induced by streptozotocin in adult male Sprague-Dawley rats. Two weeks after diabetes induction, kidney function in terms of glomerular filtration rate, and total, cortical, and medullary renal blood flows were evaluated under thiobutabarbital anesthesia during baseline and after renal artery infusion of two doses of the adenosine reuptake inhibitor dilazep. Dilazep did not affect mean arterial pressure indicating that the effects of the interventions were intrarenal. Diabetics had increased glomerular filtration rate compared with controls and dilazep dose-dependently decreased glomerular filtration rate in diabetics, whereas it had no significant effect in controls. Dilazep increased cortical renal blood flows in controls, whereas medullary blood flow was not significantly changed. Dilazep did not affect total renal blood flow in any of the groups but decreased cortical blood flow in diabetics, resulting in decreased filtration fraction by dilazep in diabetics. Pretreatment with the adenosine A2a antagonist ZM241385 prevented intrarenal dilazep-mediated effects on glomerular filtration rate and filtration fraction in diabetics. In conclusion, enhancing intrarenal adenosine signaling by dilazep normalizes diabetes-induced glomerular hyperfiltration at least in part by activation of adenosine A2a receptors.
Feeding during hibernation shifts gene expression toward active season levels in brown bears (Ursus arctos)
Authors: Perry Blair W. , McDonald Anna L. , Trojahn Shawn , Saxton Michael W. , Vincent Ellery P. , Lowry Courtney , Evans Hutzenbiler Brandon D. , Cornejo Omar E. , Robbins Charles T. , Jansen Heiko T. , Kelley Joanna L.
Published: July 2023

Hibernation in bears involves a suite of metabolical and physiological changes, including the onset of insulin resistance, that are driven in part by sweeping changes in gene expression in multiple tissues. Feeding bears glucose during hibernation partially restores active season physiological phenotypes, including partial resensitization to insulin, but the molecular mechanisms underlying this transition remain poorly understood. Here, we analyze tissue-level gene expression in adipose, liver, and muscle to identify genes that respond to midhibernation glucose feeding and thus potentially drive postfeeding metabolical and physiological shifts. We show that midhibernation feeding stimulates differential expression in all analyzed tissues of hibernating bears and that a subset of these genes responds specifically by shifting expression toward levels typical of the active season. Inferences of upstream regulatory molecules potentially driving these postfeeding responses implicate peroxisome proliferator-activated receptor gamma (PPARG) and other known regulators of insulin sensitivity, providing new insight into high-level regulatory mechanisms involved in shifting metabolic phenotypes between hibernation and active states.
Analysis of Antimicrobial Susceptibility in Bacterial Pathogens Associated with Urinary Tract Infections from Beijing Teaching Hospital in China, 2009–2017
Authors: Xie Zeqiang , Jian Jiyong , Chen Liang
Published: July 2023

Objective. Since a urinary tract infection (UTI) is easy to relapse and difficult to treat, the antibiotic resistance rate has increased year by year in recent years. This study was to analyze the characteristics of the common pathogenic bacteria and the changes of antibiotic resistance in urinary system infection, so as to guide the standard use of antibiotics in a clinical urinary tract infection and control nosocomial infection effectively. Methods. A total of 5,669 strains of a urinary tract infection in the hospital from January 2009 to December 2017 were retrospectively analyzed. Bacterial identification and the antibiotic sensitivity test (AST) were analyzed by using a VITEK-2 Compact system. Results. Of the 5669 pathogens, 3,256 (57.44%) of the strains were Gram-negative bacteria (GNB), 1,474 (26%) were Gram-positive bacteria (GPB), and 939 (16.56%) were fungi. Resistant rates of ESBL-producing strains were all significantly different from non-ESBL-producing strains in Escherichia coli (

p
<
0.05

). The resistance rate of ESBL-producing strains to β-lactam antibiotics was all higher than that of non-ESBL-producing strains in Klebsiella pneumoniae (

p
<
0.05

). The detection rate of vancomycin-resistantEnterococcus faecium and Enterococcus faecalis was 37.3% and 3.1%, respectively, and the detection rate of linezolid-resistantEnterococcus faecium and Enterococcus faecalis was 0.68% and 0%, respectively. The drug resistance rate of candida sp. to fluconazole, itraconazole, and voriconazole was 1.7%, 8.5%, and 3.4%, respectively. No amphotericin B-resistant strains were detected in the research. Conclusions. Among the 5669 strains isolated from urinary tract infection patients, GNB were the main pathogens. Escherichia coli was the major pathogen. The resistance rate of ESBLs-producingEscherichia coli was higher than that of non-ESBLs-producingEscherichia coli in general; meanwhile, β-lactam/β-lactamase inhibitors and carbapenems maintained good antimicrobial activity against Escherichia coli. The resistance rate of non-ESBLs-producingKlebsiella pneumoniae strains was significantly higher than that of ESBLs-producingKlebsiella pneumoniae strains, and drug resistance was more prominent; most of the antibiotic resistance rates were over 50%. The antimicrobial resistance rate of Enterococcus faecium was significantly higher than that of Enterococcus faecalis. There were rare linezolid-resistant strains. The antimicrobial resistance rate of imidazole to fungi was controlled less than 10%.
Antibacterial Activity of Eight Medicinal Plants from the Traditional Pharmacopoeia of Niger
Authors: Abdoulahi Mahamane Idi Issa , Yanick Kevin Melogmo Dongmo , Lauve Rachel Tchokouaha Yamthe , Habibou Hama Hamadou , Sahabi Bakasso , Abdelkader Alio Sanda , Boyom Fabrice Fekam , Tidjani Ilagouma Amadou
Published: July 2023

The emergence of multidrug bacterial resistance poses a great public health problem and requires a constant search for new antibacterial agents. However, Niger’s flora possesses several medicinal plants used in traditional medicine to cure infectious diseases and can be used as sources of bioactive ingredients. This current study was designed to evaluate the antibacterial activity of eight plants used in the traditional pharmacopeia of Niger. The extracts were prepared by maceration using ethanol, methanol, and distilled water. The obtained extracts were screened against Salmonella spp., Shigella spp., and Escherichia coli using the microdilution method coupled with a resazurin-based assay. Phytochemical screening was performed using colorimetry, while the quantification of total polyphenols, total flavonoids, and total tannins was determined by spectrophotometry. Out of the eight plants obtained, five named Cassia italica, Limeum pterocarpum, Phyllanthus pentandrus, Strychnos innocua, and Ximenia americanum exhibited antibacterial activity with MICs ranging from 500 μg/mL to 2000 μg/mL. Phytochemical screening showed the presence of alkaloids, saponosides, tannins, flavonoids, terpenes/sterols, quinones, and polyphenols. The ethanolic and methanolic extracts of X. americana contained important quantities of total polyphenols, with 43.59 ± 0.15 and 41.97 ± 0.02 mg EAG/100 mg of extract, respectively. These extracts showed the highest contents of total tannins at 46.49 g/L and 45.52 g/L, respectively. For total flavonoids, the highest content was obtained with the methanolic extract of P. pentandrus, with 3.12 ± 0.01 mg QE/100 mg of extract. These findings justify the uses of these plants in traditional medicine for the treatment of infectious diseases such as diarrhea and can be used as starting points for the development of phytodrugs against infectious diarrhea.
Seismic Performance of Precast Concrete Column-to-Column Joint Using the Steel Plate Hoop and Bolts Connection
Authors: Yuan Dawei , Shang Qi , Han Chun , Sun Jianpeng , Li Qingning
Published: July 2023

The traditional precast concrete column-to-column connections are widely used in the prefabricated concrete frame structures in China. However, many studies on the column-to-column joints have demonstrated their complex forms and poor construction efficiency. To overcome these shortcomings, a new type column–column connection with steel plate hoop and bolts was designed and proposed. In order to reveal the seismic performance of this new type connection, four precast concrete columns and two cast-in-situ columns were tested by cyclic lateral loading. They were compared and analyzed from the aspects of test phenomenon, failure mode, load–displacement relationship, strength, and stiffness degradation. The results showed that the prefabricated columns with this new type connection had the same seismic performance as the cast-in-place columns. Additionally, the strain curves of longitudinal reinforcement, stirrups, and steel plate hoops were presented, and the force transmission mode of this novel connection was analyzed. The results indicated that the innovative connection had reliable force transmission mode, which can provide reference for the application of prefabricated frame structure in the earthquake area.
Size-Dependent Chlorinated Nitrogen-Doped Carbon Nanotubes: Their Use as Electrochemical Detectors for Catechol and Resorcinol
Authors: Maboya Winny Kgabo , Rantho Mologadi Nkiyasi
Published: July 2023

In this study, various-sized nitrogen-doped carbon nanotubes (NCNTs) were fabricated by varying the concentration of chlorine in the feed. The diameter of the NCNTs was found to influence the sensing ability of the nanomaterials when coated onto the glassy carbon electrode (GCE) and used for the detection of catechol (CC) and resorcinol (RS). Larger diameter NCNTs (denoted NCNTs (2 : 1)) were produced when a low concentration of chlorine was added into the acetonitrile feed, whereas smaller diameter NCNTs (denoted NCNTs (1 : 2)) were produced when a large concentration of chlorine was added. This investigation revealed that the addition of controllable amounts of chlorine during the fabrication of NCNTs led to the creation of nanostructures with different properties. The greatest current response which was evidenced by an enhanced anodic peak of CC and RS was obtained when GCE was coated with NCNTs (2 : 1), and this was attributed to their large diameter and high graphitic nature which facilitated electron transfer as evidenced by scanning electron microscopy (SEM), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS) analysis. A linear response was obtained when varying the concentration of both CC and RS, with the limits of detection of about 0.059 μM (CC) and 0.034 μM (RS) (3S/M) obtained.
Topical Nitric Acid Burns: Initial Assessment and Management
Authors: Laanaya Asmaa , Ami Ali Mehdi , Miqdadi Amal , Noussair Mustapha , Nafaa Mourad , Belyamani Lahcen
Published: July 2023

Nitric acid (NA) is corrosive. On contact with the skin, liquid splashes with nitric acid and may produce severe burns. These burns usually take on a characteristic yellowish hue. We report the case of a 54-year-old man presenting a nitric acid burn with a pathognomonic skin lesion and perfect healing. NA is a chemical that is important in industry, and it is a very strong acid that is used for engraving, metal refining, electroplating, and fertilizer manufacturing. Skin contact with NA leads to severe burns. The pathophysiology depends on the type of concentration, the strength, quality, and duration of contact, and the penetration power of the acids concerned. The early and abundant irrigation with water or sterile isotonic saline solution, the use of panthenol-containing creams and covering with silver sulphadiazine dressing, carefully monitoring wounds, keeping wounds clean and moist, and preventing and managing secondary infection allow the healing.
An Inflammatory Checkpoint Generated by IL1RN Splicing Offers Therapeutic Opportunity for KRAS-Mutant Intrahepatic Cholangiocarcinoma
Authors: Zhang Mao , Huang Yingying , Pan Jiaomeng , Sang Chen , Lin Youpei , Dong Liangqing , Shen Xia , Wu Yingcheng , Song Guohe , Ji Shuyi , Liu Fen , Wang Mengcheng , Zheng Yuyan , Zhang Sirui , Wang Zefeng , Ren Jianke , Gao Daming , Zhou Jian , Fan Jia , Wei Wu , Lin Jian , Gao Qiang
Published: July 2023

KRAS mutations are causally linked to protumor inflammation and are identified as driving factors in tumorigenesis. Here, using multiomics data gathered from a large set of patients, we showed that KRAS mutation was associated with a specific landscape of alternative mRNA splicing that connected to myeloid inflammation in intrahepatic cholangiocarcinoma (iCCA). Then, we identified a negative feedback mechanism in which the upregulation of interleukin 1 receptor antagonist (IL1RN)-201/203 due to alternative splicing confers vital anti-inflammatory effects in KRAS-mutant iCCA. In KRAS-mutant iCCA mice, both IL1RN-201/203 upregulation and anakinra treatment ignited a significant antitumor immune response by altering neutrophil recruitment and phenotypes. Furthermore, anakinra treatment synergistically enhanced anti–PD-1 therapy to activate intratumoral GZMB+ CD8+ T cells in KRAS-mutant iCCA mice. Clinically, we found that high IL1RN-201/203 levels in patients with KRAS-mutant iCCA were significantly associated with superior response to anti–PD-1 immunotherapy.

Significance:

This work describes a novel inflammatory checkpoint mediated by IL1RN alternative splicing variants that may serve as a promising basis to develop therapeutic options for KRAS-mutant iCCA and other cancers.

This article is featured in Selected Articles from This Issue, p. 2109
Clinicopathological Characteristics and Impacts on Clinical Outcomes of Thrombotic Microangiopathy Lesions in Patients with Immunoglobulin A Nephropathy in Thailand
Authors: Puapatanakul Pongpratch , Banjongjit Athiphat , Kanjanabuch Talerngsak , Surintrspanont Jerasit , Iampenkhae Kroonpong , Praditpornsilpa Kearkiat , Eiam-Ong Somchai , Boonpucknavig Vijitr
Published: July 2023

Introduction: More reports of thrombotic microangiopathy (TMA) in immunoglobulin A (IgA) nephropathy suggest its association with poor clinical outcomes. However, the prevalence and clinical significance of TMA in IgA nephropathy have not been widely studied in different populations. Methods: Kidney biopsies of all patients with primary IgA nephropathy from 1995 to 2015 at the King Chulalongkorn Memorial Hospital, Thailand, were retrospectively reviewed and reclassified by two pathologists following the Oxford MEST-C classification. TMA lesions were detected based solely on light microscopic findings. Associations between the presence of TMA and clinical data, other pathologic findings, and clinical outcomes were studied. Results: Among 267 patients with primary IgA nephropathy, 166 had adequate clinical data and kidney tissues for the analysis. TMA was observed in 21 patients (13%) and was associated with higher mean arterial pressure (MAP), history of malignant hypertension, higher proteinuria, and lower estimated glomerular filtration rate (eGFR) at diagnosis compared to those without TMA. According to the Oxford MEST-C classification, TMA showed a significant association with severe tubular atrophy/interstitial fibrosis (T2) but not with mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), or crescents (C1–2). After a median follow-up of 50 months, patients with TMA had a significantly higher risk of progression to end-stage kidney disease (ESKD) (hazard ratio [HR] 5.8, 95% confidence interval [CI]: 3.1–10.9) and all-cause mortality (HR 3.4, 95% CI: 1.3–8.8). After adjusting for baseline eGFR, MAP, proteinuria, and other pathological lesions, TMA remained an independent predictor of ESKD (adjusted HR 2.4, 95% CI: 1.1–5.4). Conclusions: Kidney TMA in IgA nephropathy is associated with advanced disease stages, carries a poor prognosis, and thus should be considered in the pathological classification of IgA nephropathy.
Ecological Validity of the Montreal Cognitive Assessment in Non-Demented Parkinson’s Disease Patients
Authors: Aiello Edoardo Nicolò , D’Iorio Alfonsina , Solca Federica , Torre Silvia , Colombo Eleonora , Maranzano Alessio , De Lorenzo Alberto , Patisso Valerio , Treddenti Mauro , Morelli Claudia , Doretti Alberto , Maderna Luca , Verde Federico , Ferrucci Roberta , Barbieri Sergio , Ruggiero Fabiana , Priori Alberto , Silani Vincenzo , Ticozzi Nicola , Santangelo Gabriella , Ciammola Andrea , Poletti Barbara
Published: July 2023

Background: The ecological validity of performance-based cognitive screeners needs to be tested in order for them to be fully recommended for use within clinical practice and research. Objectives: The objective of this study was to examine, within an Italian cohort of non-demented Parkinson’s disease (PD) patients, the ecological validity of the Montreal Cognitive Assessment (MoCA) by assessing its association with (1) functional independence (FI), (2) quality of life (QoL), and (3) behavioural-psychological (BP) outcomes. Methods: Seventy-four non-demented PD patients were administered the MoCA and underwent motor functional – i.e., Unified Parkinson’s Disease Rating Scale (UPDRS), Modified Hoehn-Yahr Scale (HY), and Schwab and England Scale (SES) –, behavioural and psychological – i.e., State- and Trait-Anxiety Inventory-Form Y (STAI-Y1/-Y2), Beck Depression Inventory (BDI), and Dimensional Apathy Scale (DAS) – and QoL evaluations – i.e., MOS 36-Item Short Form Health Survey (SF-36). Associations of interest against FI, QoL, and BP outcomes were tested via Bonferroni-corrected Pearson’s/Spearman’s correlations while covarying for demographics, disease duration as well as UPDRS-III, UPDRS-IV, and HY scores. Intake of psychotropic drugs was also covaried when assessing the association between the MoCA and BP/QoL measures. Results: MoCA scores were significantly associated with the SES (rs(73) = 0.34; p = 0.005) and the DAS-Executive (r(67) = −0.47; p < 0.001), while not to other FI/BP outcomes and QoL measures. Conclusions: The MoCA is a valid estimate of daily life functional autonomy in non-demented PD patients, also reflecting apathetic features of a dysexecutive nature.
Implementing Preeclampsia Screening in Switzerland (IPSISS): First Results from a Multicentre Registry
Authors: Trottmann Fabienne , Challande Pauline , Manegold-Brauer Gwendolin , Ardabili Sara , Hösli Irene , Schönberger Heidrun , Amylidi-Mohr Sofia , Kohl Joachim , Hodel Markus , Surbek Daniel , Raio Luigi , Mosimann Beatrice
Published: July 2023

Introduction: The Fetal Medicine Foundation (FMF) London developed a first trimester combined screening algorithm for preterm preeclampsia (pPE) that allows a significantly higher detection of pregnancies at risk compared to conventional screening by maternal risk factors only. The aim of this trial is to validate this screening model in the Swiss population in order to implement this screening into routine first trimester ultrasound and to prescribe low-dose aspirin 150 mg (LDA) in patients at risk for pPE. Therefore, a multicentre registry study collecting and screening pregnancy outcome data was initiated in 2020; these are the preliminary results. Methods: Between June 1, 2020, and May 31, 2021, we included all singleton pregnancies with pPE screening at the hospitals of Basel, Lucerne, and Bern. Multiple of medians of uterine artery pulsatility index (UtA-PI), mean arterial pressure (MAP), placental growth factor (PlGF), and pregnancy-associated plasma protein A (PAPP-A) as well as risks were analysed as calculated by each centre’s software and recalculated on the FMF online calculator for comparative reasons. Statistical analyses were performed by GraphPad Version 9.1. Results: During the study period, 1,027 patients with singleton pregnancies were included. 174 (16.9%) had a risk >1:100 at first trimester combined screening. Combining the background risk, MAP, UtA-PI, and PlGF only, the cut-off to obtain a screen positive rate (SPR) of 11% is ≥1:75. Outcomes were available for 968/1,027 (94.3%) of all patients; 951 resulted in live birth. Fifteen (1.58%) developed classical preeclampsia (PE), 23 (2.42%) developed PE according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) definition. Conclusion: First trimester combined screening for PE and prevention with LDA results in a low prevalence of PE. The screening algorithm performs according to expectations; however, the cut-off of >1:100 results in a SPR above the accepted range and a cut-off of ≥1:75 should be considered for screening. More data are needed to evaluate, if these results are representative for the general Swiss population.
Fotografias como instrumento motivador de divulgação das geociências: a experiência da oficina “Mapa Geológico do estado do Rio de Janeiro”
Authors: Guedes Eliane , Oliveira Felipe Martins de , Matos Suzana , Quadros Patrícia , Mayato Bruna
Published: July 2023

Conectar e transmitir o conhecimento geocientífico à sociedade é um desafio aos geocientistas. O conteúdo precisa ser divulgado de maneira simples, sem prolixidade, mas também sem perder o rigor semântico científico. A geologia é uma área pouco compreendida pela população, mas a quem incute grande curiosidade com a utilização dos recursos didáticos corretos. O trabalho descreve a elaboração e aplicação de uma oficina de geociências para divulgação científica. Ela tem como base um mapa geológico simplificado do estado do Rio de Janeiro e utiliza fotografias de atrativos turísticos naturais e/ou construídos, rochas, minerais e sedimentos como recursos de apoio para ilustrar a geologia representada no mapa. Neste trabalho, relatamos nossa experiência durante a aplicação da atividade e detalhamos as principais questões levantadas pelo público participante.
Dronedarone Versus Sotalol in Antiarrhythmic Drug–Naive Veterans With Atrial Fibrillation
Authors: Pundi Krishna , Fan Jun , Kabadi Shaum , Din Natasha , Blomström-Lundqvist Carina , Camm A. John , Kowey Peter , Singh Jagmeet P. , Rashkin Jason , Wieloch Mattias , Turakhia Mintu P. , Sandhu Alexander T.
Published: July 2023

BACKGROUND:

Sotalol and dronedarone are both used for maintenance of sinus rhythm for patients with atrial fibrillation. However, while sotalol requires initial monitoring for QT prolongation and proarrhythmia, dronedarone does not. These treatments can be used in comparable patients, but their safety and effectiveness have not been compared head to head. Therefore, we retrospectively evaluated the effectiveness and safety using data from a large health care system.

METHODS:

Using Veterans Health Administration data, we identified 11 296 antiarrhythmic drug–naive patients with atrial fibrillation prescribed dronedarone or sotalol in 2012 or later. We excluded patients with prior conduction disease, pacemakers or implantable cardioverter-defibrillators, ventricular arrhythmia, cancer, renal failure, liver disease, or heart failure. We used natural language processing to identify and compare baseline left ventricular ejection fraction between treatment arms. We used 1:1 propensity score matching, based on patient demographics, comorbidities, and medications, and Cox regression to compare strategies. To evaluate residual confounding, we performed falsification analysis with nonplausible outcomes.

RESULTS:

The matched cohort comprised 6212 patients (3106 dronedarone and 3106 sotalol; mean [±SD] age, 71±10 years; 2.5% female; mean [±SD] CHA
2
DS
2
-VASC, 2±1.3). The mean (±SD) left ventricular ejection fraction was 55±11 and 58±10 for dronedarone and sotalol users, correspondingly. Dronedarone, compared with sotalol, did not demonstrate a significant association with risk of cardiovascular hospitalization (hazard ratio, 1.03 [95% CI, 0.88–1.21]) or all-cause mortality (hazard ratio, 0.89 [95% CI, 0.68–1.16]). However, dronedarone was associated with significantly lower risk of ventricular proarrhythmic events (hazard ratio, 0.53 [95% CI, 0.38–0.74]) and symptomatic bradycardia (hazard ratio, 0.56 [95% CI, 0.37–0.87]). The primary findings were stable across sensitivity analyses. Falsification analyses were not significant.

CONCLUSIONS:

Dronedarone, compared with sotalol, was associated with a lower risk of ventricular proarrhythmic events and conduction disorders while having no difference in risk of incident cardiovascular hospitalization and mortality. These observational data provide the basis for prospective efficacy and safety trials.
Initial Experience With Intercostal Insertion of an Extravascular ICD Lead Compatible With Existing Pulse Generators
Authors: Burke Martin C. , Knops Reinoud E. , Reddy Vivek , Aasbo Johan , Husby Michael , Marcovecchio Alan , O’Connor Mark , Sanghera Rick , Scheck Don , Pepplinkhuizen Shari , Ebner Adrian
Published: July 2023

BACKGROUND:

This study assessed safety and feasibility of a novel extravascular implantable cardioverter defibrillator (ICD) lead when inserted anteriorly through a rib space and connected to various commercially available ICD pulse generators (PGs) placed in either a left mid-axillary or left pectoral pocket. Currently available or investigational, extravascular-ICDs include a subcutaneous or subxiphoid lead connected to customized extravascular-ICD PGs.

METHODS:

This novel extravascular-ICD (AtaCor Medical Inc, San Clemente, CA) employs a unique intercostal implant technique and is designed to function with commercial DF-4 ICD PGs. In this nonrandomized, single-center, acute study, 36 de novo or replacement ICD (transvenous ICD) patients enrolled to receive a concomitant extravascular-ICD lead inserted through an intercostal space along the left parasternal margin. extravascular-ICD leads were connected to DF-4 compatible ICD PGs positioned in either a left mid-axillary or pectoral pocket for acute sensing and defibrillation testing. Defibrillation testing started at 30 Joules (J) and stepped up or down in 5 to 10 joule increments depending on the success and limitations of the generator used.

RESULTS:

Successful acute defibrillation using ≤35 J was noted in 100% of left mid-axillary PG subjects (n=27, mean 16.3±8.6 J) and 83% of left pectoral PG subjects (n=6, mean 21.0±8.4 J). Furthermore, 24 of 27 (89%) of patients tested with a left, mid-axillary intermuscular PG had successful VF conversion with defibrillation energies at least 10 J below the maximum delivered output of the device. All evaluable episodes (n=93) were automatically sensed, detected, and shocked. No serious device-related intraoperative adverse events were observed.

CONCLUSIONS:

This first-in-human study documented the safe and reliable placement of a novel extravascular ICD lead with effective sensing and defibrillation of induced ventricular fibrillation using commercial DF-4 ICD PGs.
Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes
Authors: Packer Milton , Wilcox Christopher S. , Testani Jeffrey M.
Published: July 2023

SGLT2 (sodium-glucose cotransporter 2) inhibitors interfere with the reabsorption of glucose and sodium in the early proximal renal tubule, but the magnitude and duration of any ensuing natriuretic or diuretic effect are the result of an interplay between the degree of upregulation of SGLT2 and sodium-hydrogen exchanger 3, the extent to which downstream compensatory tubular mechanisms are activated, and (potentially) the volume set point in individual patients. A comprehensive review and synthesis of available studies reveals several renal response patterns with substantial variation across studies and clinical settings. However, the common observation is an absence of a large acute or chronic diuresis or natriuresis with these agents, either when given alone or combined with other diuretics. This limited response results from the fact that renal compensation to these drugs is rapid and nearly complete within a few days or weeks, preventing progressive volume losses. Nevertheless, the finding that fractional excretion of glucose and lithium (the latter being a marker of proximal sodium reabsorption) persists during long-term treatment with SGLT2 inhibitors indicates that pharmacological tolerance to the effects of these drugs at the level of the proximal tubule does not meaningfully occur. This persistent proximal tubular effect of SGLT2 inhibitors can be hypothesized to produce a durable improvement in the internal set point for volume homeostasis, which may become clinically important during times of fluid expansion. However, it is difficult to know whether a treatment-related change in the volume set point actually occurs or contributes to the effect of these drugs to reduce the risk of major heart failure events. SGLT2 inhibitors exert cardioprotective effects by a direct effect on cardiomyocytes that is independent of the presence of or binding to SGLT2 or the actions of these drugs on the proximal renal tubule. Nevertheless, changes in the volume set point mediated by SGLT2 inhibitors might potentially act cooperatively with the direct favorable molecular and cellular effects of these drugs on cardiomyocytes to mediate their benefits on the development and clinical course of heart failure.