bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment switch in Fabry disease- a matter of dose?
Authors: Lenders Malte , Nordbeck Peter , Canaan-Kühl Sima , Kreul Lukas , Duning Thomas , Lorenz Lora , Pogoda Christian , Brand Stefan-Martin , Wanner Christoph , Brand Eva 
Published: June 2020

BackgroundPatients with Fabry disease (FD) on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in chronic kidney disease epidemiology collaboration-based estimated glomerular filtration rate (eGFR) and a worsened plasma lyso-Gb3 decrease. Hence, the most effective dose is still a matter of debate.MethodsIn this prospective observational study, we assessed end-organ damage and clinical symptoms in 78 patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, which were assigned to continue this treatment (agalsidase-beta, regular-dose group, n=17); received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa (switch group, n=22); or were re-switched to agalsidase-beta after receiving agalsidase-alfa for 12 months (re-switch group, n=39) with a follow-up of 88±25 months.ResultsNo differences for clinical events were observed for all groups. Patients within the re-switch group started with the worst eGFR values at baseline (p=0.0217). Overall, eGFR values remained stable in the regular-dose group (p=0.1052) and decreased significantly in the re-switch and switch groups (p<0.0001 and p=0.0052, respectively). However, in all groups males presented with an annual loss of eGFR by –2.9, –2.5 and −3.9 mL/min/1.73 m² (regular-dose, re-switch, switch groups, all p<0.05). In females, eGFR decreased significantly only in the re-switch group by −2.9 mL/min/1.73 m² per year (p<0.01). Lyso-Gb3 decreased in the re-switch group after a change back to agalsidase-beta (p<0.05).ConclusionsOur data suggest that a re-switch to high dosage of agalsidase results in a better biochemical response, but not in a significant renal amelioration especially in classical males.
ACE2 and COVID-19 and the resulting ARDS
Authors: Zhang Xiaoqing , Li Shuren , Niu Shaoqian 
Published: June 2020

AbstractThis article reviews the correlation between ACE2 and COVID-19 and the resulting acute respiratory distress syndrome (ARDS). ACE2 is a crucial component of the renin-angiotensin system (RAS). The classical ACE-angiotensin Ⅱ (Ang II)-angiotensin type 1 receptor (AT1R) axis and the ACE2-Ang(1-7)-Mas counter-regulatory axis play an essential role in RAS system. ACE2 antagonises the activation of the classical RAS ACE-Ang II-AT1R axis and protects against lung injury. Similar to severe acute respiratory syndrome-related coronavirus, 2019 novel coronavirus (2019-nCoV) also uses ACE2 for cell entry. ARDS is a clinical high-mortality disease which is probably due to the excessive activation of RAS caused by 2019-nCoV infection, and ACE2 has a protective effect on ARDS caused by COVID-19. Because of these protective effects of ACE2 on ARDS, the development of drugs enhancing ACE2 activity may become one of the most promising approaches for the treatment of COVID-19 in the near future. In the meantime, however, the use of RAS blockers such as ACE inhibitors and angiotensin II receptor blockers that inhibit the damaging (ACE-Ang II) arm of the RAS cascade in the lung may also be promising. Trial registration number: NCT04287686.
Identifying the nature of the QCD transition in relativistic collision of heavy nuclei with deep learning
Authors: Du Yi-Lun , Zhou Kai , Steinheimer Jan , Pang Long-Gang , Motornenko Anton , Zong Hong-Shi , Wang Xin-Nian , Stöcker Horst 
Published: June 2020

AbstractUsing deep convolutional neural network (CNN), the nature of the QCD transition can be identified from the final-state pion spectra from hybrid model simulations of heavy-ion collisions that combines a viscous hydrodynamic model with a hadronic cascade “after-burner”. Two different types of equations of state (EoS) of the medium are used in the hydrodynamic evolution. The resulting spectra in transverse momentum and azimuthal angle are used as the input data to train the neural network to distinguish different EoS. Different scenarios for the input data are studied and compared in a systematic way. A clear hierarchy is observed in the prediction accuracy when using the event-by-event, cascade-coarse-grained and event-fine-averaged spectra as input for the network, which are about 80%, 90% and 99%, respectively. A comparison with the prediction performance by deep neural network (DNN) with only the normalized pion transverse momentum spectra is also made. High-level features of pion spectra captured by a carefully-trained neural network were found to be able to distinguish the nature of the QCD transition even in a simulation scenario which is close to the experiments.
Synchrotron radiation in terms of accelerator for CEPC MDI
Authors: Bai Sha , Yu Chenghui , Wang Yiwei , Gao Jie 
Published: June 2020

With the discovery of the Higgs boson at around 125 GeV, a circular Higgs factory design with high luminosity [Formula: see text] is becoming more popular in the accelerator world. The Circular Electron and Positron Collider (CEPC) project in China is one of them. Machine Detector Interface (MDI) is the key research area in electron–positron colliders, especially in CEPC. Since the [Formula: see text] beams collide at the Interaction Point (IP) with a horizontal angle of 33 mrad, the horizontal trajectory will couple to the vertical. Due to the solenoid and anti-solenoid combined field strength quite high, the maximum could be up to 4.2 T, the transverse magnetic field component is also quite high. Thus synchrotron radiation (SR) from vertical trajectory in combined field should be taken into account. And also synchrotron radiation is an important influential factor in the collimator design of CEPC MDI. These two effects are analyzed in this paper.
Design and beam dynamics of the CEPC booster
Authors: Wang Dou , Yu Chenghui , Cui Xiaohao , Ji Daheng , Liu Yudong , Zhai Jiyuan , Wang Na , Zhang Yuan , Gao Jie 
Published: June 2020

The CEPC booster needs to provide electron and positron beams to the collider at different energy with required injection speed. A 10 GeV linac is adopted as the injector for CDR. Then the beam energy is accelerated to specific energy according to three modes of operation of the CEPC collider ring ([Formula: see text], [Formula: see text] and [Formula: see text]). The geometry of the booster is designed carefully in order to share the same tunnel with the collider. The design status of the booster with the CDR lattice including parameters, optics and dynamic aperture is discussed in this paper.
Targeting MEF2D-fusion Oncogenic Transcriptional Circuitries in B-cell Precursor Acute Lymphoblastic Leukemia
Authors: Tsuzuki Shinobu , Yasuda Takahiko , Kojima Shinya , Kawazu Masahito , Akahane Koshi , Inukai Takeshi , Imaizumi Masue , Morishita Takanobu , Miyamura Koichi , Ueno Toshihide , Karnan Sivasundaram , Ota Akinobu , Hyodo Toshinori , Konishi Hiroyuki , Sanada Masashi , Nagai Hirokazu , Horibe Keizo , Tomita Akihiro , Suzuki Kyogo , Muramatsu Hideki , Takahashi Yoshiyuki , Miyazaki Yasushi , Matsumura Itaru , Kiyoi Hitoshi , Hosokawa Yoshitaka , Mano Hiroyuki , Hayakawa Fumihiko 
Published: June 2020

Abstract

The cellular context that integrates gene expression, signaling, and metabolism dictates the oncogenic behavior and shapes the treatment responses in distinct cancer types. Although chimeric fusion proteins involving transcription factors (TF) are hallmarks of many types of acute lymphoblastic leukemia (ALL), therapeutically targeting the fusion proteins is a challenge. In this work, we characterize the core regulatory circuitry (CRC; interconnected autoregulatory loops of TFs) of B-ALL involving MEF2D-fusions and identify MEF2D-fusion and SREBF1 TFs as crucial CRC components. By gene silencing and pharmacologic perturbation, we reveal that the CRC integrates the pre-B-cell receptor (BCR) and lipid metabolism to maintain itself and govern malignant phenotypes. Small-molecule inhibitors of pre-BCR signaling and lipid biosynthesis disrupt the CRC and silence the MEF2D fusion in cell culture and show therapeutic efficacy in xenografted mice. Therefore, pharmacologic disruption of CRC presents a potential therapeutic strategy to target fusion protein–driven leukemia.

Significance:
Cancer type–specific gene expression is governed by transcription factors involved in a highly interconnected autoregulatory loop called CRC. Here, we characterized fusion protein–driven CRC and identified its pharmacologic vulnerabilities, opening therapeutic avenues to indirectly target fusion-driven leukemia by disrupting its CRC.
See related commentary by Sadras and Müschen, p. 18.
This article is highlighted in the In This Issue feature, p. 5
Genomic Characterization of HIV-Associated Plasmablastic Lymphoma Identifies Pervasive Mutations in the JAK–STAT Pathway
Authors: Liu Zhaoqi , Filip Ioan , Gomez Karen , Engelbrecht Dewaldt , Meer Shabnum , Lalloo Pooja N. , Patel Pareen , Perner Yvonne , Zhao Junfei , Wang Jiguang , Pasqualucci Laura , Rabadan Raul , Willem Pascale 
Published: June 2020

AbstractPlasmablastic lymphoma (PBL) is an aggressive B-cell non-Hodgkin lymphoma associated with immunodeficiency in the context of human immunodeficiency virus (HIV) infection or iatrogenic immunosuppression. While a rare disease in general, the incidence is dramatically increased in regions of the world with high HIV prevalence. The molecular pathogenesis of this disease is poorly characterized. Here, we defined the genomic features of PBL in a cohort of 110 patients from South Africa (15 by whole-exome sequencing and 95 by deep targeted sequencing). We identified recurrent mutations in genes of the JAK–STAT signaling pathway, including STAT3 (42%), JAK1 (14%), and SOCS1 (10%), leading to its constitutive activation. Moreover, 24% of cases harbored gain-of-function mutations in RAS family members (NRAS and KRAS). Comparative analysis with other B-cell malignancies uncovered PBL-specific somatic mutations and transcriptional programs. We also found recurrent copy number gains encompassing the CD44 gene (37%), which encodes for a cell surface receptor involved in lymphocyte activation and homing, and was found expressed at high levels in all tested cases, independent of genetic alterations. These findings have implications for the understanding of the pathogenesis of this disease and the development of personalized medicine approaches.Significance:Plasmablastic lymphoma is a poorly studied and extremely aggressive tumor. Here we define the genomic landscape of this lymphoma in HIV-positive individuals from South Africa and identify pervasive mutations in JAK–STAT3 and RAS–MAPK signaling pathways. These data offer a genomic framework for the design of improved treatment strategies targeting these circuits.See related commentary by Küppers, p. 23.This article is highlighted in the In This Issue feature, p. 5
Exercise Capacity and Ventricular Remodeling After Transcatheter Ventricular Septal Defect Closure in Asymptomatic or Minimally Symptomatic Adolescents and Adults
Authors: Chen Chun-An , Wang Jou-Kou , Lin Ming-Tai , Chiu Hsin-Hui , Hsu Jui-Yu , Lin Shu-Man , Chang Ya-Mei , Chiu Shuenn-Nan , Lu Chun-Wei , Wu Mei-Hwan , Yang Ming-Chun 
Published: June 2020

Background:
Transcatheter ventricular septal defect (VSD) closure is a safe and efficacious alternative to surgery. However, its benefits in asymptomatic or minimally symptomatic patients remain unknown.

Methods:
Sixty patients with VSD aged 12 to 60 years underwent cardiopulmonary exercise test and echocardiography 1 day before transcatheter VSD closure and 6 months after intervention (closure group). Thirty patients who did not receive the intervention underwent the same evaluations over 6 months (observation group).

Results:

No significant change in exercise function was observed after VSD closure, except for increased peak oxygen (O
2
) pulse (absolute increase: 0.4±1.4 mL/beat). Left ventricular end-diastolic dimension and mitral peak early filling velocity-to-early diastolic annular velocity ratio decreased (absolute decrease: 0.3±0.6 cm and 0.7±1.9, respectively). Despite unchanged overall peak O
2
consumption, 33% of closure group patients exhibited clinically significant improvements in peak O
2
consumption (>10% increase relative to baseline). This was not related to the pulmonary flow-to-systemic flow ratio or baseline exercise capacity. By contrast, all exercise function parameters deteriorated significantly in the observation group. Subgroup analysis revealed that patients with a baseline left ventricular end-diastolic dimension
Z
score of >2 exhibited a significantly greater improvement in peak O
2
consumption, peak O
2
pulse, and oxygen uptake efficiency slope than did the observation group.

Conclusions:

Compared with conservative management, transcatheter VSD closure prevents deterioration in exercise capacity and promotes left ventricular reverse remodeling in asymptomatic or minimally symptomatic patients. These benefits are most prominent in patients whose left ventricular end-diastolic dimension
Z
score before intervention is >2, irrespective of baseline peak O
2
consumption and pulmonary flow/systemic flow ratio.

Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT03127748.
Can the plant immune system be activated against animal parasites such as nematodes?
Authors: Molinari Sergio 
Published: June 2020

Summary
Plants have an immune system that can be exerted by every cell against a vast array of pathogens and parasites. This immune system has several levels of specialisation. A first level induces a general basal defence, after which specific pathogen-associated molecular patterns (PAMPs) are recognised by plant receptors. Normally, this basal defence is overcome by specialised pests by secreting specific effectors that suppress this first line of defence. Plant-parasitic nematodes have been found to secrete several such effectors through amphid and cuticle secretions or directly into the cells through their stylets. Many studies carried out on endoparasitic sedentary nematodes (ESN), in particular, reported the suppression of plant defence, especially in terms of down-regulation of the genes involved in salicylic acid (SA)-mediated defence, in the very first stages of plant-nematode interaction. However, plants can be immunised or primed against nematode attacks. Immunised plants respond to nematode infection more rapidly and efficiently and let a minor number of invasive juveniles become sedentary, develop to gravid females and reproduce. Immunisation of plants can be achieved by pre-treatments with chemicals that are functional analogues of the phytohormones that mediate defence reactions, such as salicylic acid (SA). Moreover, plants provided with the beneficial microorganisms commonly present in a healthy rhizosphere, such as arbuscular mycorrhizal fungi or opportunistic symbiotic fungi, have been found to be immunised against ESN. Immunisation is mainly mediated by up-regulation of SA-dependent defence genes, such as pathogenesis-related genes (PR-genes). Immunisation is systemic and can also work against herbivorous insects.
A review of the leafhopper genus Pseudosubhimalus Ghauri (Hemiptera: Cicadellidae: Deltocephalinae) with description of a new species from Pakistan
Authors: NAVEED HASSAN , SHAH BISMILLAH , ZHANG YALIN 
Published: June 2020

A new species of the leafhopper genus Pseudosubhimalus Ghauri (Cicadellidae: Deltocephalinae: Cicadulini), Pseudosubhimalus pakistanicus sp. n., is described from Khyber Pakhtunkhwa Province, Pakistan. Figures for habitus and genitalic characters are given for this new species and newly recorded species from Pakistan. A key to all the known species of the genus Pseudosubhimalus is provided.
Taxonomy of some Boreoheptagyiini Brundin (Diptera: Chironomidae: Diamesinae) from the mountains of Central Asia and the Middle East, with description and DNA barcoding of new taxa
Authors: MAKARCHENKO EUGENYI A.  , SEMENCHENKO ALEXANDER A. , PALATOV DMITRY M. 
Published: June 2020

Chironomids of the tribe Boreoheptagyiini from the mountains of Iran, China and East Kazakhstan are revised using both morphological characters and partial DNA sequences of the mitochondrial cytochrome c oxidase subunit I gene. Using adult males, Palatovia lorestanica gen. nov. sp. nov., as well as Boreoheptagyia iranica sp. nov. both from Iran (Lorestan Province, Zagros Mountains), B. joeli sp. nov. from China (Tien Shan Mountains), and B. sarymsactyensis sp. nov. from Eastern Kazakhstan (Kazakh Mountain Altai), are described and figured. A brief redescription of the rare species B. brevitarsis (Tokunaga) from Iran (Mazandaran Province), previously known only from Japan, is also given. The DNA barcoding analysis shows well-supported genetic divergence between all studied taxa (four species of the genus Boreoheptagyia and one of Palatovia). Combining DNA barcodes obtained in this study with available sequences in GenBank, the phylogenetic relationships of the tribe Boreoheptagyiini are reconstructed. In the resulting Bayesian and maximum likelihood (ML) tree the polyphyly of the genus Boreoheptagyia is recognized. B. iranica is placed as a sister species to P. lorestanica, despite the lack of confirmation of their morphological similarity.
Utility of Second-Look Endoscopy with Debridement After Pediatric Functional Endoscopic Sinus Surgery in Patients with Cystic Fibrosis
Authors: Helmen Zachary M. , Little Ryan E. , Robey Thomas 
Published: June 2020

Objectives: To determine the utility of Second-look endoscopy with debridement (SLED) after functional endoscopic sinus surgery (ESS) in pediatric cystic fibrosis (CF) patients. To compare outcomes in pediatric CF patients undergoing sinus surgery for chronic sinusitis with or without SLED. To describe findings present at the time of SLED. Methods: Retrospective chart review of 61 ESS procedures performed at a tertiary care pediatric center from 2013 to 2016. Data collected included demographics, SLED findings, and 6-month pre-/postoperative disease specific outcomes including incidence of sinonasal and pulmonary exacerbations and revisions. Results: Sixty-one cases were reviewed. SLED was performed in 38 cases on average 22.4 days postoperatively. Average preoperative Lund-Mackay score was 14.9 and 14.8 among patients undergoing ESS with and without SLED, respectively. Pre-/postoperative intranasal steroid use and extent of surgery performed was similar among all patients. At the time of SLED, rates of synechiae, polyps and maxillary antrostomy obstruction were 26.3%, 23.7%, and 7.9%, respectively. The incidence and number of days to onset of postoperative sinonasal exacerbations requiring antibiotic therapy within 6 months of ESS were 1.0 (SD 1.0) and 85 days (SD 45.7); and 1.3 (SD 1.0) and 80.4 days (SD 40.5) for patients undergoing ESS with and without SLED, respectively ( P value .33). The number of days to first pulmonary exacerbation was 113.9 (SD 45.5) and 47.4 (SD 34.1) among SLED and non-SLED patients, respectively ( P value .01). No significant difference was observed in revision rates and time to revision ESS (30% and overall average 1.4 years, respectively). Conclusion: The utility of SLED among pediatric CF patients remains unclear. While debridement did not have a significant impact on sinonasal exacerbations or revision rates, pulmonary exacerbations for patients undergoing SLED were delayed. Further studies are needed to clarify the impact of SLED.
Analyzing the Bidirectional Relationship between Tourism Growth and Economic Development
Authors: Pulido-Fernández Juan Ignacio , Cárdenas-García Pablo Juan 
Published: June 2020

After having demonstrated the relationship between tourism and economic growth, tourism-led economic growth (TLGH), and economic-driven tourism growth (EDTG), the scientific literature was concerned with studying the relationship between tourism and economic development, limiting itself to analyzing a possible unidirectional relationship between tourism, economic growth, and economic development. In this context, the aim of this article is to determine if the relationship between tourism and economic development is bidirectional given that, although tourism can be a tool for economic development, it is also true that a higher level of economic development influences tourism growth. Using a sample of 143 countries, and applying confirmatory factor analysis together with a structural equations model, the bidirectional relationship is confirmed. Therefore, although tourism growth and economic development face different challenges, if public policies work in a coordinated manner, they may contribute significantly to improving economic development in countries that are configured as tourist destinations.
Clinical impact of multi-parameter continuous non-invasive monitoring in hospital wards: a systematic review and meta-analysis
Authors: Sun Lin , Joshi Meera , Khan Sadia N , Ashrafian Hutan , Darzi Ara 
Published: June 2020

Objective Delayed response to clinical deterioration as a result of intermittent vital sign monitoring is a cause of preventable morbidity and mortality. This review focuses on the clinical impact of multi-parameter continuous non-invasive monitoring of vital signs (CoNiM) in non-intensive care unit patients. Design Systematic review and meta-analysis of primary studies. Embase, MEDLINE, HMIC, PsycINFO and Cochrane were searched from April 1964 to 18 June 2019 with no language restriction. Setting The search was limited to hospitalised, non-intensive care unit adult patients who had two or more vital signs continuously monitored. Participants All primary studies that evaluated the clinical impact of using multi-parameter CoNiM in adult hospital wards outside of the intensive care unit. Main outcome measures Clinical impact of multi-parameter CoNiM. Results This systematic review identified 14 relevant studies from 3846 search results. Five studies were classified as Group A – associations found between measured vital signs and clinical parameters. Nine studies were classified as Group B – comparison between clinical outcomes of patients with and without multi-parameter CoNiM. Vital signs data from CoNiM were found to associate with type of presenting complaint, level of renal function and incidence of major clinical events. CoNiM also assisted in diagnosis by differentiating between patients with acute heart failure, stroke and sepsis (with sub-clustering of septic patients). In the meta-analysis, patients on multi-parameter CoNiM had a 39% decrease in risk of mortality (risk ratio [RR] 0.61; 95% confidence interval [95% CI] 0.39, 0.95) when compared to patients with regular intermittent monitoring. There was a trend of reduced intensive care unit transfer (RR 0.86; 95% CI 0.67, 1.11) and reduced rapid response team activation (RR 0.61; 95% CI 0.26–1.43). A trend towards reduced hospital length of stay was also found using weighted mean difference (WMD –3.32 days; 95% CI -8.82–2.19 days). Conclusion There is evidence of clinical benefit in implementing CoNiM in non-intensive care unit patients. This review supports the use of multi-parameter CoNiM outside of intensive care unit with further large-scale RCTs required to further affirm clinical impact.