bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological and exercise‐induced activation of AMPK as emerging therapies for myotonic dystrophy type 1 patients
Authors: Ravel‐Chapuis Aymeric , Duchesne Elise , Jasmin Bernard J. 
Published: June 2022

AbstractMyotonic dystrophy type 1 (DM1) is a multisystemic disorder with variable clinical features. Currently, there is no cure or effective treatment for DM1. The disease is caused by an expansion of CUG repeats in the 3′ UTR of DMPK mRNAs. Mutant DMPK mRNAs accumulate in nuclei as RNA foci and trigger an imbalance in the level and localization of RNA‐binding proteins causing the characteristic missplicing events that account for the varied DM1 symptoms, a disease mechanism referred to as RNA toxicity. In recent years, multiple signalling pathways have been identified as being aberrantly regulated in skeletal muscle in response to the CUG expansion, including AMPK, a sensor of energy status, as well as a master regulator of cellular energy homeostasis. Converging lines of evidence highlight the benefits of activating AMPK signalling pharmacologically on RNA toxicity, as well as on muscle histology and function, in preclinical DM1 models. Importantly, a clinical trial with metformin, an activator of AMPK, resulted in functional benefits in DM1 patients. In addition, exercise, a known AMPK activator, has shown promising effects on RNA toxicity and muscle function in DM1 mice. Finally, clinical trials involving moderate‐intensity exercise also induced functional benefits for DM1 patients. Taken together, these studies clearly demonstrate the molecular, histological and functional benefits of AMPK activation and exercise‐based interventions on the DM1 phenotype. Despite these advances, several key questions remain; in particular, the extent of the true implication of AMPK in the observed beneficial improvements, as well as how, mechanistically, activation of AMPK signalling improves the DM1 pathophysiology.
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An Investigation of Performance and Emissions of Diesel Engine Using Heterogeneous Catalyst Jatropha Biodiesel: A Sustainable Model Using Taguchi and Response Surface Methodology
Authors: Singh Aparna , Choudhary Akhilesh Kumar , Sinha Shailendra 
Published: June 2022

Abstract
Excessive consumption of fossil fuels has exacerbated global warming and led to an increase in air pollution levels in the environment. The increasing oil demand prompted recent research to explore the future application of alternative, eco-friendly fuels for diesel engines. Jatropha biodiesel has been produced from JCO, using heterogeneous catalyst (CaO) through transesterification process. In this study, the performance and emission characteristics of an engine powered by a Jatropha biodiesel blends have been investigated. The application of response surface methodology (RSM) coupled with Taguchi method for optimization of engine input parameters is promising approach to derive the most accurate optimized models for output responses. Input parameters such as biodiesel blend, load, CR, and FIP were selected, experiments were designed as per L18 orthogonal array in Taguchi, and CCFCD L20 design matrix for RSM methodology. Injection timing is an essential engine characteristic, which has a considerable effect on the ordering emissions. If injection is done early, the starting air temperature and pressure are lower, which means the ignition delay will rise. The ignition delay may begin at any time after the injection begins, resulting in somewhat increased temperature and pressure initially but which then rapidly declines as the ignition delay progresses. The optimal setting of engine input parameters is recorded at 270 bar fuel injection pressure, compression ratio of 18, 7.61 kg load, and 25% blend of Jatropha biodiesel with diesel for optimum BTHE, BMEP, BSFC, Pmax, CO, and NOx emissions. Experimental results are compared with optimum output responses and deviations are found within the accepted range of errors.
Automatic segmentation of multitype retinal fluid from optical coherence tomography images using semisupervised deep learning network
Authors: Li Feng , Pan WenZhe , Xiang Wenjie , Zou Haidong 
Published: June 2022

Background/aimsTo develop and validate a deep learning model for automated segmentation of multitype retinal fluid using optical coherence tomography (OCT) images.MethodsWe retrospectively collected a total of 2814 completely anonymised OCT images with subretinal fluid (SRF) and intraretinal fluid (IRF) from 141 patients between July 2018 and June 2020, constituting our in-house retinal OCT dataset. On this dataset, we developed a novel semisupervised retinal fluid segmentation deep network (Ref-Net) to automatically identify SRF and IRF in a coarse-to-refine fashion. We performed quantitative and qualitative analyses on the model’s performance while verifying its generalisation ability by using our in-house retinal OCT dataset for training and an unseen Kermany dataset for testing. We also determined the importance of major components in the semisupervised Ref-Net through extensive ablation. The main outcome measures were Dice similarity coefficient (Dice), sensitivity (Sen), specificity (Spe) and mean absolute error (MAE).ResultsOur model trained on a handful of labelled OCT images manifested higher performance (Dice: 81.2%, Sen: 87.3%, Spe: 98.8% and MAE: 1.1% for SRF; Dice: 78.0%, Sen: 83.6%, Spe: 99.3% and MAE: 0.5% for IRF) over most cutting-edge segmentation models. It obtained expert-level performance with only 80 labelled OCT images and even exceeded two out of three ophthalmologists with 160 labelled OCT images. Its satisfactory generalisation capability across an unseen dataset was also demonstrated.ConclusionThe semisupervised Ref-Net required only la few labelled OCT images to generate outstanding performance in automate segmentation of multitype retinal fluid, which has the potential for providing assistance for clinicians in the management of ocular disease.
Impact of COVID-19 on patients awaiting ablation for atrial fibrillation
Authors: Pius Charlene , Ahmad Hasan , Snowdon Richard , Ashrafi Reza , Waktare Johan EP , Borbas Zoltan , Luther Vishal , Mahida Saagar , Modi Simon , Hall Mark , Gupta Dhiraj , Todd Derick 
Published: June 2022

ObjectiveAtrial fibrillation (AF) ablation services were significantly affected by the COVID-19 pandemic. We aimed to evaluate a symptom-based clinician prioritisation scheme for waiting list management compared with patient-completed quality of life (QoL) scores. We also sought to understand factors influencing QoL, particularly the impact of COVID-19, on patients awaiting AF ablation, via a bespoke questionnaire.MethodsPatients awaiting AF ablation were sent two QoL questionnaires (Atrial Fibrillation Effect on QualiTy of Life (AFEQT) and EuroQol 5D (EQ5D-5L)) and the bespoke questionnaire. At a separate time point, patients were categorised as C1—urgent, C2—priority or C3—routine by their cardiologist based on review of clinic letters.ResultsThere were 118 patients included with priority categorisation available for 86 patients. Median AFEQT scores were lower in C2 (30.4; 17.2–51.9) vs C3 patients (56.5; 32.1–74.1; p<0.01). Unplanned admission occurred in 3 patients in C3 with AFEQT scores of <40. Although 65 patients had AF symptoms during the pandemic, 43.1% did not seek help where they ordinarily would have. An exercise frequency of ≥3–4 times a week was associated with higher AFEQT (56.5; 41.2–74.1; p<0.001) and EQ5D (0.84; 0.74–0.88; p<0.0001) scores.ConclusionThe QoL of patients awaiting AF ablation is impaired and AFEQT helps to identify patients at risk of admission, over and above physician assessment. COVID-19 influenced patients seeking medical attention with symptomatic AF when they normally would. Regular exercise is associated with better QoL in patients awaiting AF ablation.
Excise taxes and pricing activities of e-liquid products sold in online vape shops
Authors: Ma Shaoying , Jiang Shuning , Ling Meng , Lu Bo , Chen Jian , Shang Ce 
Published: June 2022

BackgroundAlthough e-cigarette excise taxes have great potential to prevent the initiation and escalation of e-cigarette use, little information is available on pricing activities of online vape shops, and how well taxation is implemented during web-based sales remains unclear.ObjectivesWe examine e-liquid pricing activities in popular online vape shops that sell nationwide in the USA and present how those stores charge excise taxes based on shipping addresses in states and local jurisdictions that have e-cigarette taxation in place.MethodsWe collect e-liquid sales prices from five online vape shops using web data extraction, standardise prices for e-liquid products, and present e-liquid price distribution in the whole sample and in each store, as well as variations of excise taxes across states/local jurisdictions and between stores. The price data were scraped from the store websites from February to May in 2021.ResultsWe collected data on 14 477 e-liquid products from five stores. The average price of e-liquids is $0.25/mL, and the median price is $0.20/mL in our sample. E-liquid products sold online are very affordable and the average prices are lower compared with price estimates using other sources (eg, self-reports, sales data). In addition, online stores charge state excise taxes inconsistently and fail to comply with county-level or city-level excise taxes.ConclusionE-liquid products sold online are priced low, and stricter enforcement of e-cigarette excise tax is needed in online purchasing channels.
Resolving naked singularities in $$\alpha ^{\prime }$$-corrected string theory
Authors: Ying Shuxuan 
Published: June 2022

AbstractLow energy effective action of bosonic string theory possesses a kind of singular static solution which can be interpreted as a naked singularity. Based on the Hohm–Zwiebach action, the naked singularities could be smoothed out by introducing the complete $$\alpha ^{\prime }$$

α
′

corrections of string theory. In this paper, we present two sets of non-singular solutions, which are also regular everywhere in the Einstein frame. In the perturbative region $$\alpha ^{\prime }\rightarrow 0$$

α
′

→
0

, the solutions reduce to the perturbative results. Our result provides extra evidence for weak cosmic censorship conjecture (WCCC) from a viewpoint of string theory.
Event topology and constituent-quark scaling of elliptic flow in heavy-ion collisions at the Large Hadron Collider using a multiphase transport model
Authors: Mallick Neelkamal , Tripathy Sushanta , Sahoo Raghunath 
Published: June 2022

AbstractTransverse spherocity is an event shape observable, which separates the events based on their geometrical shapes. In this work, we use transverse spherocity to study the identified light flavor production in heavy-ion collisions using A Multi-Phase Transport (AMPT) model. We obtain the elliptic flow coefficients for pions, kaons and protons in Pb+Pb collisions at $$\sqrt{s_\mathrm{{NN}}} = 5.02$$

s
NN

=
5.02

TeV as a function of transverse spherocity and collision centrality. Also, we study the number of constituent-quark (NCQ) scaling of elliptic flow which interprets the dominance of the quark degrees of freedom at the early stages of the collision. We observe a clear dependence of the elliptic flow for identified particles on transverse spherocity. It is found that the NCQ-scaling is strongly violated in events with low transverse spherocity compared to transverse spherocity-integrated events, confirming the fragmentation-based hadronization mechanism for high-momentum partons involved in the dynamics of jetty-like events.
A test of the evolution of gas depletion factor in galaxy clusters using strong gravitational lensing systems
Authors: Holanda R. F. L. , Bora Kamal , Desai Shantanu 
Published: June 2022

AbstractIn this work, we discuss a new method to probe the redshift evolution of the gas depletion factor, i.e. the ratio by which the gas mass fraction of galaxy clusters is depleted with respect to the universal mean of baryon fraction. The dataset we use for this purpose consists of 40 gas mass fraction measurements measured at $$r_{2500}$$

r
2500

using Chandra X-ray observations, strong gravitational lensing sub-samples obtained from SLOAN Lens ACS + BOSS Emission-line Lens Survey (BELLS) + Strong Legacy Survey SL2S + SLACS. For our analysis, the validity of the cosmic distance duality relation is assumed. We find a mildly decreasing trend for the gas depletion factor as a function of redshift at about 2.7$$\sigma $$
σ
.
Constitutive Activation of the Tumor Suppressor p53 in Hepatocytes Paradoxically Promotes Non–Cell Autonomous Liver Carcinogenesis
Authors: Makino Yuki , Hikita Hayato , Fukumoto Kenji , Sung Ji Hyun , Sakano Yoshihiro , Murai Kazuhiro , Sakane Sadatsugu , Kodama Takahiro , Sakamori Ryotaro , Kondo Jumpei , Kobayashi Shogo , Tatsumi Tomohide , Takehara Tetsuo 
Published: June 2022

Abstract

In chronic liver diseases (CLD), p53 is constitutively activated in hepatocytes due to various etiologies as viral infection, ethanol exposure, or lipid accumulation. This study was aimed to clarify the significance of p53 activation on the pathophysiology of CLDs. In Kras-mutant liver cancer model, murine double minute 2 (Mdm2), a negative regulator of p53, was specifically deleted in hepatocytes [Alb-Cre KrasLSL-G12D Mdm2fl/fl (LiKM; KrasG12D mutation and Mdm2 loss in the liver)]. Accumulation of p53 and upregulation of its downstream genes were observed in hepatocytes in LiKM mice. LiKM mice showed liver inflammation accompanied by hepatocyte apoptosis, senescence-associated secretory phenotype (SASP), and the emergence of hepatic progenitor cells (HPC). More importantly, Mdm2 deletion promoted non–cell autonomous development of liver tumors. Organoids generated from HPCs harbored tumor-formation ability when subcutaneously inoculated into NOD/Shi-scid/IL2Rγ (null) mice. Treatment with acyclic retinoid suppressed growth of HPCs in vitro and inhibited tumorigenesis in LiKM mice. All of the phenotypes in LiKM mice, including accelerated liver tumorigenesis, were negated by further deletion of p53 in hepatocytes (Alb-Cre KrasLSL-G12D Mdm2fl/fl p53fl/fl). Activation of hepatic p53 was noted in liver biopsy samples obtained from 182 patients with CLD, in comparison with 23 normal liver samples without background liver diseases. In patients with CLD, activity of hepatic p53 was positively correlated with the expression of apoptosis, SASP, HPC-associated genes and tumor incidence in the liver after biopsy. In conclusion, activation of hepatocyte p53 creates a microenvironment prone to tumor formation from HPCs. Optimization of p53 activity in hepatocytes is important to prevent patients with CLD from hepatocarcinogenesis.

Significance:
This study reveals that activation of p53 in hepatocytes promotes liver carcinogenesis derived from HPCs, which elucidates a paradoxical aspect of a tumor suppressor p53 and novel mechanism of liver carcinogenesis.
See related commentary by Barton and Lozano, p. 2824
WEE1 Inhibition Augments CDC7 (DDK) Inhibitor–induced Cell Death in Ewing Sarcoma by Forcing Premature Mitotic Entry and Mitotic Catastrophe
Authors: Martin Jeffrey C. , Sims Jennie R. , Gupta Ajay , Bakin Andrei V. , Ohm Joyce Ellen 
Published: June 2022

Ewing sarcoma is an aggressive childhood cancer for which treatment options remain limited and toxic. There is an urgent need for the identification of novel therapeutic strategies. Our group has recently shown that Ewing cells rely on the S-phase kinase cell division cycle 7 (CDC7) DBF4-dependent kinase (DDK) to maintain replication rates and cell viability and that DDK inhibition causes an increase in the phosphorylation of CDK1 and a significant delay in mitotic entry. Here, we expand on our previous findings and show that DDK inhibitor–induced mitotic entry delay is dependent upon WEE1 kinase. Specifically, WEE1 phosphorylates CDK1 and prevents mitotic entry upon DDK inhibition due to the presence of underreplicated DNA, potentially limiting the cytotoxic effects of DDK inhibition. To overcome this, we combined the inhibition of DDK with the inhibition of WEE1 and found that this results in elevated levels of premature mitotic entry, mitotic catastrophe, and apoptosis. Importantly, we have found that DDK and WEE1 inhibitors display a synergistic relationship with regards to reducing cell viability of Ewing sarcoma cells. Interestingly, the cytotoxic nature of this combination can be suppressed by the inhibition of CDK1 or microtubule polymerization, indicating that mitotic progression is required to elicit the cytotoxic effects. This is the first study to display the potential of utilizing the combined inhibition of DDK and WEE1 for the treatment of cancer. We believe this will offer a potential therapeutic strategy for the treatment of Ewing sarcoma as well as other tumor types that display sensitivity to DDK inhibitors.Significance:Ewing sarcoma is an aggressive pediatric cancer for which chemotherapy is very intense and often results in acute toxicities. Here, we have found that the combined inhibition of CDC7 kinase (DDK) and WEE1 kinase forces high levels of mitotic errors and synergistic cell death, specifically in Ewing sarcoma cells. This combination has the potential to provide a highly efficacious and minimally toxic treatment strategy for patients with Ewing sarcoma.
Ansiedade, depressão e desesperança no cuidador familiar de pacientes com alterações neuropsicológicas
Authors: Nobre Isadora Di Natale , Lemos Carolina dos Santos , Pardini Adriana Cristina Guimarães , Carvalho Janaína de , Salles Isabel Chateaubriand Diniz 
Published: June 2022

Objetivo: Identificar a incidência de ansiedade, depressão e desesperança em 54 cuidadores familiares de pacientes com alteração neuropsicológica após lesão encefálica ocorrida na idade adulta. Métodos: Trata-se de um estudo observacional com corte transversal e análise quantitativa, desenvolvido em um centro de reabilitação (Associação de Assistência à Criança Deficiente - AACD) localizado na cidade de São Paulo. Foram aplicados os instrumentos: Inventário de Ansiedade Beck (BAI), Inventário de Depressão Beck (BDI) e Escala de Desesperança Beck (BHS), juntamente com um questionário de caracterização da amostra. Resultados: Os dados foram analisados estatisticamente e dos familiares entrevistados 55,6% apresentou índices de ansiedade, 20,4% apresentou depressão e 31,5% desesperança. Conclusão: Os cuidadores familiares desta pesquisa apresentaram relevante sofrimento psíquico, apontando a necessidade de ações voltadas especificamente a eles nos programas de reabilitação.
Estresse infantil e a percepção do suporte familiar das crianças submetidas à cirurgia ortopédica
Authors: Nakao Gabriella Ribeiro , Ito Paula Hiromi , Pontes Rafael Oliveira , Costa Regina Célia Villa 
Published: June 2022

Objetivo: Investigar a correlação existente entre o nível de estresse de crianças pós-operadas, de 11 a 14 anos de idade, em relação à qualidade da percepção destes pacientes sobre o suporte familiar recebido durante o processo de reabilitação física. Método: Trata-se de um estudo transversal, com análise qualitativa e quantitativa, desenvolvido em um centro de reabilitação, no município de São Paulo. Os instrumentos aplicados nos pacientes foram: Escala de Stress Infantil (ESI), Inventário de Percepção do Suporte Familiar (IPSF) e no respectivo cuidador, um questionário de caracterização dos participantes. Resultados: Os dados foram analisados estatisticamente e se observou significância estatística entre o fator Adaptação (IPSF) com a dimensão Reações psicológicas com componente depressivo (ESI). Houve associação significativa entre o escore total da ESI e do IPSF. Neste estudo, das crianças com sinais significativos de estresse, a maioria apresentou baixa/ médio-baixa percepção do suporte familiar. Discussão: A percepção do paciente sobre o meio pelo qual se relaciona é um importante indício do enfrentamento às situações adversas vividas no meio social, conforme associação encontrada neste estudo. Conclusão: Os aspectos relacionados à maturidade cognitiva e emocionais da criança contribuem na qualidade da percepção do suporte familiar. É importante que novos estudos sejam realizados para ampliar as discussões nessa área
Noun2Verb: Probabilistic Frame Semantics for Word Class Conversion
Authors: Yu Lei , Xu Yang 
Published: June 2022

Abstract
Humans can flexibly extend word usages across different grammatical classes, a phenomenon known as word class conversion. Noun-to-verb conversion, or denominal verb (e.g., to Google a cheap flight), is one of the most prevalent forms of word class conversion. However, existing natural language processing systems are impoverished in interpreting and generating novel denominal verb usages. Previous work has suggested that novel denominal verb usages are comprehensible if the listener can compute the intended meaning based on shared knowledge with the speaker. Here we explore a computational formalism for this proposal couched in frame semantics. We present a formal framework, Noun2Verb, that simulates the production and comprehension of novel denominal verb usages by modeling shared knowledge of speaker and listener in semantic frames. We evaluate an incremental set of probabilistic models that learn to interpret and generate novel denominal verb usages via paraphrasing. We show that a model where the speaker and listener cooperatively learn the joint distribution over semantic frame elements better explains the empirical denominal verb usages than state-of-the-art language models, evaluated against data from (1) contemporary English in both adult and child speech, (2) contemporary Mandarin Chinese, and (3) the historical development of English. Our work grounds word class conversion in probabilistic frame semantics and bridges the gap between natural language processing systems and humans in lexical creativity.
Low-noise delta-sigma analog front end with capacitor swapping technique for capacitive microsensors
Authors: Nam Kyeongsik , Kim Hyungseup , Choi Gyuri , Yoo Mookyoung , Ko Hyoungho 
Published: June 2022

In this paper, low-noise incremental delta–sigma analog front end (AFE) integrated circuit (IC) for capacitive microsensors is presented. A conventional capacitance-to-digital converter (CDC) mainly uses a multi-stage capacitive sensing amplified stage (CSA) and analog-to-digital converters. The multi-stage CSA is not suitable for application in various Internet of things (IoT) devices that require low power because the power consumption of the analog front-end circuit increases in proportion to the number of amplifiers and the chip area increases. So, the presented delta-sigma AFE can convert the capacitance changes to the digital codes directly. This structure can achieve a small active area and low power consumption. The delta–sigma AFE achieves low-noise and high linearity using a capacitor polarity swapping technique. The measured effective resolution is 16.2 bits, and the non-linearity is 0.05% full-scale output (FSO). The integrated circuit is implemented in a 0.18-µm standard CMOS process. All functional blocks, including the analog circuits (bandgap reference, voltage reference, and delta–sigma capacitance-to-digital converter) and digital block (accumulator and timing generator), are integrated on a chip. The proposed incremental delta–sigma AFE consumes 1.12 mW of power from a 3.3-V supply at a sampling frequency of 500 kHz and occupies a total active area of 0.42 mm2.