bluuebunny/crossref_metadata_2025 huggingface dataset:
How to Manage Type 2 Diabetes Mellitus During the COVID-19 Pandemic: Let’s Hear the Patient’s Voice
Authors: Lusher Joanne , Cameron Dawn
Published: December 2021

Diabetes is one of the most significant comorbidities associated with COVID-19 susceptibility and severity, and recent statistics have identified that up to half of all individuals with COVID-19 have had diabetes. Over 90% of people with Type 2 diabetes mellitus are overweight or obese, and obesity itself increases the severity of COVID-19 and the risk of needing intensive care and ventilation. Careful glycaemic control improves outcomes for individuals with diabetes and also significantly reduces risks if they become infected with COVID-19. It is, therefore, essential that research focuses on effective ways in which to manage Type 2 diabetes mellitus during this global pandemic. What healthcare professionals focus their attention and resources on is also crucial to its niftiness and, considering that patient self-management is key to effective glycaemic control, it makes sense that healthcare practitioners call on the patient for some advice.
New Long-Life Concrete Pavements in the Czech Republic
Authors: Slánský Bohuslav , Šmilauer Vit , Hlavatý Jiří , Dvořák Richard
Published: December 2021

A jointed plain concrete pavement represents a reliable, historically proven technical solution for highly loaded roads, highways, airports and other industrial surfaces. Excellent resistance to permanent deformations (rutting) and also durability and maintenance costs play key roles in assessing the economic benefits, rehabilitation plans, traffic closures, consumption and recycling of materials. In the history of concrete pavement construction, slow-to-normal hardening Portland cement was used in Czechoslovakia during the 1970s-1980s. The pavements are being replaced after 40-50 years of service, mostly due to vertical slab displacements due to missing dowel bars. However, pavements built after 1996 used rapid hardening cements, resulting in long-term surface cracking and decreased durability. In order to build durable concrete pavements, slower hardening slag-blended binders were designed and tested in the restrained ring shrinkage test and in isothermal calorimetry. Corresponding concretes were tested mainly for the compressive/tensile strength evolution and deicing salt-frost scaling to meet current specifications. The pilot project was executed on a 14 km highway, where a unique temperature-strain monitoring system was installed to provide long-term data from the concrete pavement. A thermo-mechanical coupled model served for data validation, showing a beneficial role of slower hydration kinetics. Continuous monitoring interim results at 24 months have revealed small curling induced by drying and the overall small differential shrinkage of the slab.
Análise do Programa Nacional de Alimentação Escolar (PNAE) em Passo Fundo (RS) no período de 2009 a 2017
Authors: Dias Lopes Indaia
Published: December 2021

Recebido: 13/04/2019

Aprovado: 02/06/2020

Este trabalho busca identificar como ocorreu o desenvolvimento do Programa Nacional de Alimentação Escolar (PNAE) no município de Passo Fundo, no estado do Rio Grande do Sul, a partir da implementação da Lei nº 11.947/2009. Essa legislação determinou que, no mínimo 30% dos recursos destinados ao PNAE pelo Fundo Nacional de Educação (FNDE) devem ser investidos em produtos da agricultura familiar. Com a implementação da Lei n° 11.947/2009 ocorreu a organização de fornecedores da agricultura familiar em Passo Fundo. Tanto por parte do órgão responsável pela alimentação escolar na prefeitura municipal, quanto dos agricultores que fornecem produtos para estes locais, decorreu um tempo para que os mesmos pudessem se adaptar e atender as exigências propostas por essa Lei. Ainda existem entraves a serem superados para aprimorar este mercado em Passo Fundo, mas é a partir da interação entre os diferentes atores sociais envolvidos com o PNAE que pode-se alcançar melhores resultados.

Palavras-chave: Alimentação escolar. Agricultura Familiar. Passo Fundo.
O Desafio Chinês Para A África
Authors: Klein Magno
Published: December 2021

Recebida: 11/08/2020

Aprovada: 07/12/2020
A Secure Two Factor Authentication Protocol for Cloud-Assisted Wireless Body Area Network Using Blockchain
Authors: Ujil Jacqualine Cristhy
Published: December 2021

The recent advancements in technologies have allowed us to come so far and resulted in many breakthroughs. One of the various examples is internet of things, wireless communication, and cloud computing which can be useful if utilize in many fields. In the field of medical, these advancements allowed any medical centres to improve patient’s health remotely simply by using wearable devices on patients that then will amalgamate with the wireless body area network (WBAN). However, WBAN has limited resources which limits its services. To solve this problem, cloud computing is used to provide storage and computation. Unfortunately, these methods allow the system to be vulnerable to various malicious attacks. Attackers can easily gain access to the medical records of patients hence the integrity of security and privacy of confidential data have been compromised. In this paper, we presented a secure protocol for cloud-assisted database using multi-factor authentication and blockchain as an added measure to ensure security. Accordingly, we prove that the presented scheme offers more security and privacy. Therefore, it is the most practical method to be applied in the medical field.
Biometric Blockchain-based Multifactor Privacy Perserving Authentication Scheme for VANETs
Authors: Dineal Gumis Myra Annatasha Umang , Money Travis Iran , Affandi Zetty Elica , Sapuan Siti Najihah , Tony Mastura , Safian Mohd. Haziq Qayyim , Hamka Nur Huda
Published: December 2021

To provide the most suitable or compatible scheme to work against various attack toward vehicular ad hoc networks (VANETs) is very challenging. Not only that the high authentication and communication overhead also became a problem for VANETs. Thus, in this paper we use multifactor authentication that could resist various attack toward VANETs. A biometric blockchain-based multifactor privacy-preserving authentication scheme for VANETs. This scheme is proposed by using a new robust pseudo-identity multifactor VANET scheme based on Physical Unclonable Functions (PUF) and biometric data of the vehicle’s authorized user. To calculate the computational cost and the authentication overhead, we compare three of our computational cost and authentication overhead below. From the complexity analysis this proposed scheme has a lower authentication overhead and offers better security level and a low computational cost can be achieved. From the perspective of future, we hope that the cost that involve in this scheme still can be reduce as we offer a high security level. Not only that, but we also hope that this scheme can be implemented practically.
Proteomics Profiling to Distinguish DOCK8 Deficiency From Atopic Dermatitis
Authors: Jacob Minnie , Masood Afshan , Shinwari Zakiya , Abdel Jabbar Mai , Al-Mousa Hamoud , Arnaout Rand , AlSaud Bandar , Dasouki Majed , Alaiya Ayodele A. , Abdel Rahman Anas M.
Published: December 2021

Dedicator of cytokinesis 8 deficiency is an autosomal recessive primary immune deficiency disease belonging to the group of hyperimmunoglobulinemia E syndrome (HIES). The clinical phenotype of dedicator of cytokinesis 8 (DOCK8) deficiency, characterized by allergic manifestations, increased infections, and increased IgE levels, overlaps with the clinical presentation of atopic dermatitis (AD). Despite the identification of metabolomics and cytokine biomarkers, distinguishing between the two conditions remains clinically challenging. The present study used a label-free untargeted proteomics approach using liquid-chromatography mass spectrometry with network pathway analysis to identify the differentially regulated serum proteins and the associated metabolic pathways altered between the groups. Serum samples from DOCK8 (n = 10), AD (n = 9) patients and healthy control (Ctrl) groups (n = 5) were analyzed. Based on the proteomics profile, the PLS-DA score plot between the three groups showed a clear group separation and sample clustering (R2 = 0.957, Q2 = 0.732). Significantly differentially abundant proteins (p < 0.05, FC cut off 2) were identified between DOCK8-deficient and AD groups relative to Ctrl (n = 105, and n = 109) and between DOCK8-deficient and AD groups (n = 85). Venn diagram analysis revealed a differential regulation of 24 distinct proteins from among the 85 between DOCK8-deficient and AD groups, including claspin, haptoglobin-related protein, immunoglobulins, complement proteins, fibulin, and others. Receiver-operating characteristic curve (ROC) analysis identified claspin and haptoglobin-related protein, as potential biomarkers with the highest sensitivity and specificity (AUC = 1), capable of distinguishing between patients with DOCK8 deficiency and AD. Network pathway analysis between DOCK8-deficiency and AD groups revealed that the identified proteins centered around the dysregulation of ERK1/2 signaling pathway. Herein, proteomic profiling of DOCK8-deficiency and AD groups was carried out to determine alterations in the proteomic profiles and identify a panel of the potential proteomics biomarker with possible diagnostic applications. Distinguishing between DOCK8-deficiency and AD will help in the early initiation of treatment and preventing complications.
Classification of X-Ray Attenuation Properties of Additive Manufacturing and 3D Printing Materials Using Computed Tomography From 70 to 140 kVp
Authors: Ma Xiangjie , Buschmann Martin , Unger Ewald , Homolka Peter
Published: December 2021

Additive manufacturing and 3D printing is particularly useful in the production of phantoms for medical imaging applications including determination and optimization of (diagnostic) image quality and dosimetry. Additive manufacturing allows the leap from simple slab and stylized to (pseudo)-anthropomorphic phantoms. This necessitates the use of materials with x-ray attenuation as close as possible to that of the tissues or organs mimicked. X-ray attenuation properties including their energy dependence were determined for 35 printing materials comprising photocured resins and thermoplastic polymers. Prior to measuring x-ray attenuation in CT from 70 to 140 kVp, printing parameters were thoroughly optimized to ensure maximum density avoiding too low attenuation due to microscopic or macroscopic voids. These optimized parameters are made available. CT scanning was performed in a water filled phantom to guarantee defined scan conditions and accurate HU value determination. The spectrum of HU values covered by polymers printed using fused deposition modeling reached from −258 to +1,063 at 120 kVp (−197 to +1,804 at 70 kVp, to −266 to +985 at 140 kVp, respectively). Photocured resins covered 43 to 175 HU at 120 kVp (16–156 at 70, and 57–178 at 140 kVp). At 120 kVp, ASA mimics water almost perfectly (+2 HU). HIPS (−40 HU) is found close to adipose tissue. In all photocurable resins, and 17 printing filaments HU values decreased with increasing beam hardness contrary to soft tissues except adipose tissue making it difficult to mimic water or average soft tissue in phantoms correctly over a range of energies with one single printing material. Filled filaments provided both, the HU range, and an appropriate energy dependence mimicking bone tissues. A filled material with almost constant HU values was identified potentially allowing mimicking soft tissues by reducing density using controlled under-filling. The measurements performed in this study can be used to design phantoms with a wide range of x-ray contrasts, and energy dependence of these contrasts by combining appropriate materials. Data provided on the energy dependence can also be used to correct contrast or contrast to noise ratios from phantom measurements to real tissue contrasts or CNRs.
Evaluation of the Anti-Inflammatory and Anti-Oxidative Effects of Therapeutic Human Lactoferrin Fragments
Authors: Pan Yu , Liu Zhao , Wang Yijie , Zhang Linshen , Chua Niying , Dai Lei , Chen Jun , Ho Chun Loong
Published: December 2021

Chronic inflammation is considered a pressing health issue that needs resolving. Inflammatory disease such as inflammatory bowel disease requires a long-term medical regimen to prevent disease progression. Conventionally, lactoferrin is used to treat mild gastrointestinal tract and skin inflammation. Protease-digested lactoferrin fragments often exhibit improved therapeutic properties compared to full-length lactoferrin (flHLF). However, there are no studies on the use of protease-digested lactoferrin fragments to treat inflammation. Herein, we assess the anti-inflammatory properties of engineered recombinant lactoferrin fragments (rtHLF4, rteHLF1, and rpHLF2) on non-malignant colonic fibroblast cells and colorectal cancer cells. We found that rtHLF4 is 10 times more effective to prevent inflammation compared to flHLF. These results were investigated by looking into the reactive oxygen species (ROS) production, angiogenesis activity, and cellular proliferation of the treated cells. We have demonstrated in this study the anti-inflammatory properties of the flHLF and the various lactoferrin fragments. These results complement the anti-cancer properties of these proteins that were demonstrated in an earlier study.
The Prognostic Value and Immune Landscapes of a m6A/m5C/m1A-Related LncRNAs Signature in Head and Neck Squamous Cell Carcinoma
Authors: Wang Enhao , Li Yang , Ming Ruijie , Wei Jiahui , Du Peiyu , Zhou Peng , Zong Shimin , Xiao Hongjun
Published: December 2021

Background: N6-methyladenosine (m6A), 5-methylcytosine (m5C) and N1-methyladenosine (m1A) are the main RNA methylation modifications involved in the progression of cancer. However, it is still unclear whether m6A/m5C/m1A-related long non-coding RNAs (lncRNAs) affect the prognosis of head and neck squamous cell carcinoma (HNSCC).

Methods: We summarized 52 m6A/m5C/m1A-related genes, downloaded 44 normal samples and 501 HNSCC tumor samples with RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) database, and then searched for m6A/m5C/m1A-related genes co-expressed lncRNAs. We adopt the least absolute shrinkage and selection operator (LASSO) Cox regression to obtain m6A/m5C/m1A-related lncRNAs to construct a prognostic signature of HNSCC.

Results: This prognostic signature is based on six m6A/m5C/m1A-related lncRNAs (AL035587.1, AC009121.3, AF131215.5, FMR1-IT1, AC106820.5, PTOV1-AS2). It was found that the high-risk subgroup has worse overall survival (OS) than the low-risk subgroup. Moreover, the results showed that most immune checkpoint genes were significantly different between the two risk groups (p < 0.05). Immunity microenvironment analysis showed that the contents of NK cell resting, macrophages M2, and neutrophils in samples of low-risk group were significantly lower than those of high-risk group (p < 0.05), while the contents of B cells navie, plasma cells, and T cells regulatory (Tregs) were on the contrary (p < 0.05). In addition, patients with high tumor mutational burden (TMB) had the worse overall survival than those with low tumor mutational burden.

Conclusion: Our study elucidated how m6A/m5C/m1A-related lncRNAs are related to the prognosis, immune microenvironment, and TMB of HNSCC. In the future, these m6A/m5C/m1A-related lncRNAs may become a new choice for immunotherapy of HNSCC.
Differential Role of PD-1 Expressed by Various Immune and Tumor Cells in the Tumor Immune Microenvironment: Expression, Function, Therapeutic Efficacy, and Resistance to Cancer Immunotherapy
Authors: Kim Myeong Joon , Ha Sang-Jun
Published: December 2021

In the tumor immune microenvironment (TIME), tumor cells interact with various cells and operate various strategies to avoid antitumor immune responses. These immune escape strategies often make the TIME resistant to cancer immunotherapy. Neutralizing immune escape strategies is necessary to overcome resistance to cancer immunotherapy. Immune checkpoint receptors (ICRs) expressed in effector immune cells inhibit their effector function via direct interaction with immune checkpoint ligands (ICLs) expressed in tumor cells. Therefore, blocking ICRs or ICLs has been developed as a promising cancer immunotherapy by reinvigorating the function of effector immune cells. Among the ICRs, programmed cell death 1 (PD-1) has mainly been antagonized to enhance the survival of human patients with cancer by restoring the function of tumor-infiltrating (TI) CD8+ T cells. It has been demonstrated that PD-1 is expressed not only in TI CD8+ T cells, but also in other TI immune cells and even tumor cells. While PD-1 suppresses the function of TI CD8+ T cells, it is controversial whether PD-1 suppresses or amplifies the suppressive function of TI-suppressive immune cells (e.g., regulatory T cells, tumor-associated macrophages, and myeloid cells). There is also controversy regarding the role of tumor-expressing PD-1. Therefore, a precise understanding of the expression pattern and function of PD-1 in each cell subset is important for improving the efficacy of cancer immunotherapy. Here, we review the differential role of PD-1 expressed by various TI immune cells and tumor cells. We focused on how cell-type-specific ablation or blockade of PD-1 affects tumor growth in a murine tumor model. Furthermore, we will also describe how the blockade of PD-1 acts on TI immune cells in human patients with cancer.
Targeting Splicing Factor SRSF6 for Cancer Therapy
Authors: She Wenting , Shao Jun , Jia Rong
Published: December 2021

Aberrant alternative splicing of pre-mRNA is an emerging cancer hallmark. Many cancer-associated genes undergo alternative splicing to produce multiple isoforms with diverse or even antagonistic functions. Oncogenic isoforms are often up-regulated, whereas tumor suppressive isoforms are down-regulated during tumorigenesis. Serine/arginine-rich splicing factor 6 (SRSF6) is an important splicing factor that regulates the alternative splicing of hundreds of target genes, including many cancer-associated genes. The potential roles of SRSF6 in cancers have attracted increasing attentions in the past decade. Accumulated pieces of evidence have shown that SRSF6 is a potential oncogenic gene that promotes oncogenic splicing when overexpressed. Targeting SRSF6 may suppress tumorigenesis. In this review, we describe the gene, mRNA, and protein structure of SRSF6; summarize the current understanding of the expression, functions, and regulatory mechanisms of SRSF6 during tumorigenesis; and discuss the potential application of targeting SRSF6 in cancer treatment.
TGF-β Signaling and Resistance to Cancer Therapy
Authors: Zhang Maoduo , Zhang Ying Yi , Chen Yongze , Wang Jia , Wang Qiang , Lu Hezhe
Published: December 2021

The transforming growth factor β (TGF-β) pathway, which is well studied for its ability to inhibit cell proliferation in early stages of tumorigenesis while promoting epithelial-mesenchymal transition and invasion in advanced cancer, is considered to act as a double-edged sword in cancer. Multiple inhibitors have been developed to target TGF-β signaling, but results from clinical trials were inconsistent, suggesting that the functions of TGF-β in human cancers are not yet fully explored. Multiple drug resistance is a major challenge in cancer therapy; emerging evidence indicates that TGF-β signaling may be a key factor in cancer resistance to chemotherapy, targeted therapy and immunotherapy. Finally, combining anti-TGF-β therapy with other cancer therapy is an attractive venue to be explored for the treatment of therapy-resistant cancer.
Insights Into the Detection Selectivity of Redox and Non-redox Based Probes for the Superoxide Anion Using Coumarin and Chromone as the Fluorophores
Authors: Wang Yuchen , Jia Shumi , Yu Zhenyan , Wen Hui , Cui Huaqing
Published: December 2021

In this study, we evaluated the applicability of various superoxide anion sensors which were designed based on either redox or non-redox mechanisms. Firstly, both redox- and non–redox-based superoxide anion probes were designed and synthesized using either coumarin or chromone as the fluorophores, and the photophysical properties of these probes were measured. Subsequently, the sensing preference of both types of probes toward various reactive oxygen species (ROS) was evaluated. We found that non–redox-based O2•− probes exhibited broad sensing ability toward various ROS. By contrast, redox based O2•− probes showed a clear reactivity hierarchy which was well correlated to the oxidizing strength of the ROS. Lastly, the detection selectivity of redox-based O2•− recognizing probes was also observed when balancing various factors, such as reactant ROS concentrations, temperature, and changing reaction transformation rates. Herein, we concluded the selectivity advantage of redox-based O2•− probes.
Synthesis and Discovery of Schiff Base Bearing Furopyrimidinone for Selective Recognition of Zn2+ and its Applications in Cell Imaging and Detection of Cu2+
Authors: Hu Yanggen , Luo Chao , Gui Lili , Lu Jing , Fu Juncai , Han Xinya , Ma Junkai , Luo Lun
Published: December 2021

A simplefuro [2,3-d]pyrimidinone-based Schiff base FPS was synthesized via aza-Wittig reaction and structure elucidation was carried out by spectroscopic studies FT-IR, 1H NMR, and 13C NMR and mass spectrometry. FPS showed weak fluorescence emission in methanol and the selectivity of FPS to different metal ions (Mn2+, Ca2+, Fe2+, Fe3+, Mg2+, Al3+, Ba2+, Ag+, Co2+, Na+, K+, Cu2+, Zn2+, Pb2+, Bi3+) were studied by absorption and fluorescence titration. The results show that FPS has selective fluorescence sensing behavior for Zn2+ ions and the limit of detection (LOD) was calculated to be 1.19 × 10–8 mol/L. Moreover, FPS-Zn2+ acts as a metal based highly selective and sensitive new chemosensor for Cu2+ ions and the LOD was calculated to be 2.25 × 10–7 mol/L. In accordance with the results and theoretical calculations, we suspected that the binding mechanisms of FPS to Zn2+ and Cu2+ were assigned to be the cooperative interaction of Zn2+(Cu2+)-N.
Meteorological Factors Influence the Presence of Fungi in the Air; A 14-Month Surveillance Study at an Adult Cystic Fibrosis Center
Authors: van Rhijn Norman , Coleman James , Collier Lisa , Moore Caroline , Richardson Malcolm D. , Bright-Thomas Rowland J. , Jones Andrew M.
Published: December 2021

Background

Cystic fibrosis is an inherited disease that predisposes to progressive lung damage. Cystic fibrosis patients are particularly prone to developing pulmonary infections. Fungal species are commonly isolated in lower airway samples from patients with cystic fibrosis. Fungal spores are prevalent in the air.

Methods

We performed environmental air sampling surveillance at the Manchester Adult Cystic Fibrosis Centre, UK (MACFC) over a 14-month period to assess fungal growth inside and outside the CF center.

Results

Airborne counts of fungal spores peaked from May to October, both in outdoor and indoor samples. Collection of meteorological data allowed us to correlate fungal presence in the air with elevated temperatures and low wind speeds. Additionally, we demonstrated patient rooms containing windows had elevated fungal counts compared to rooms not directly connected to the outdoors.

Conclusions

This study suggests that airborne Aspergillus fumigatus spores were more abundant during the summer months of the survey period, which appeared to be driven by increased temperatures and lower wind speeds. Indoor counts directly correlated to outdoor A. fumigatus levels and were elevated in patient rooms that were directly connected to the outdoor environment via an openable window designed for ventilation purposes. Further studies are required to determine the clinical implications of these findings for cystic fibrosis patients who are predisposed to Aspergillus related diseases, and in particular whether there is seasonal influence on incidence of Aspergillus related conditions and if screening for such complications such be increased during summer months and precautions intensified for those with a known history of Aspergillus related disease.
Profiling the Quality and Quantity of Naturally Induced Antibody Responses Against Pfs230 and Pfs48/45 Among Non-Febrile Children Living in Southern Ghana: A Longitudinal Study
Authors: Broni Fermin K. , Acquah Festus K. , Obiri-Yeboah Dorcas , Obboh Evans K. , Sarpong Esther , Amoah Linda E.
Published: December 2021

A clear understanding of the properties of naturally induced antibody responses against transmission-blocking vaccine candidates can accelerate the understanding of the development of transmission-blocking immunity. This study characterized the naturally induced IgG responses against two leading transmission-blocking vaccine antigens, Pfs230 and Pfs48/45, in non-febrile children living in Simiw, Ghana. Consecutive sampling was used to recruit 84 non-febrile children aged from 6 to 12 years old into the 6-month (November 2017 until May 2018) longitudinal study. Venous blood (1 ml) was collected once every 2 months and used to determine hemoglobin levels, P. falciparum prevalence using microscopy and polymerase chain reaction, and the levels and relative avidity of IgG responses against Pfs230 and Pfs48/45 using indirect ELISA. IgG levels against Pfs230 and Pfs48/45 decreased from the start (November) to the middle (January) and end (March) of the dry season respectively, then they began to increase. Participants, especially older children (10–12 years old) with active infections generally had lower antibody levels against both antigens. The relative avidities of IgG against both antigens followed the trend of IgG levels until the middle of the dry season, after which the relative avidities of both antigens correlated inversely with the antibody levels. In conclusion, although IgG antibody levels against both Pfs48/45 and Pfs230 began to increase by the early rainy season, they were inversely correlated to their respective relative avidities.
Scaling Biodiversity Conservation Efforts: An Examination of the Relationship Between Global Biodiversity Targets and Local Plans
Authors: Pierce Jennifer Rae , Drill Sabrina , Halder Michael D. , Tan Mika Mei Jia , Tiwari Anushri , López Guijosa Pablo A.
Published: December 2021

Cities have a critical role to play in meeting global-scale biodiversity targets. Urban socio-ecological systems connect human and ecological well-being. The outsized impact of cities reaches well-beyond their geographic borders through cultural, ecological, and economic interactions. Although cities account for just 2% of the earth's surface, they host over half of the human population and are responsible for 75% of consumption. The Parties to the Convention on Biological Diversity (CBD) and others have acknowledged the important role cities can play in achieving global targets. In response, at least 110 cities have produced plans focused on biodiversity, but we do not know the extent to which these city plans align with global targets or what role they play in achieving these targets. Here, we explore the relationship between global biodiversity conservation targets and local biodiversity plans to identify how elements at the two scales align or diverge. We compared the CBD Strategic Plan 2011–2020 (Aichi Targets) with 44 local biodiversity plans (often called LBSAPs) from cities around the world. We analyzed more than 2,800 actions from the local plans to measure the relationship with these global targets. Our results show how local approaches to biodiversity conservation can inform post-2020 global frameworks to improve coordination between global and local scale processes. We identify actions particular to the local scale that are critical to conserve global biodiversity and suggest a framework for improved coordination between actors at different scales that address their respective roles and spheres of influence.
Plasma Exosomes at the Late Phase of Remote Ischemic Pre-conditioning Attenuate Myocardial Ischemia-Reperfusion Injury Through Transferring miR-126a-3p
Authors: Li Danni , Zhao Yang , Zhang Chuyi , Wang Fan , Zhou Yan , Jin Sanqing
Published: December 2021

Background: Remote ischemic pre-conditioning (RIPC) alleviated the myocardial ischemia-reperfusion injury, yet the underlying mechanisms remain to be fully elucidated, especially at the late phase. Searching a key component as a transfer carrier may provide a novel insight into RIPC-mediated cardioprotection in the condition of myocardial ischemia-reperfusion.

Objective: To investigate the cardioprotective effect of plasma exosomes at the late phase of RIPC and its potential signaling pathways involved.

Methods and Results: Exosomes were isolated from the plasma of rats 48 h after the RIPC or control protocol. Although the total plasma exosomes level had no significant change at the late phase of RIPC (RIPC-exosome) compared with the control exosomes (Control-exosome), the RIPC-exosome afforded remarkable protection against myocardial ischemia-reperfusion (MI/R) injury in rats and hypoxia-reoxygenation (H/R) injury in cells. The miRNA array revealed significant enrichment of miR-126a-3p in RIPC-exosome. Importantly, both miR-126a-3p inhibitor and antagonist significantly blunted the cardioprotection of RIPC-exosome in H/R cells and MI/R rats, respectively, while miR-126a-3p mimic and agomir showed significant cardioprotection against H/R injury in cells and MI/R injury in rats. Mechanistically, RIPC-exosome, especially exosomal miR-126a-3p, activated the reperfusion injury salvage kinase (RISK) pathway by enhancing the phosphorylation of Akt and Erk1/2, and simultaneously inhibited Caspase-3 mediated apoptotic signaling.

Conclusions: Our findings reveal a novel myocardial protective mechanism that plasma exosomes at the late phase of RIPC attenuate myocardial ischemia-reperfusion injury via exosomal miR-126a-3p.
Heart Failure Probability and Early Outcomes of Critically Ill Patients With COVID-19: A Prospective, Multicenter Study
Authors: Gao Weibo , Fan Jiasai , Sun Di , Yang Mengxi , Guo Wei , Tao Liyuan , Zheng Jingang , Zhu Jihong , Wang Tianbing , Ren Jingyi
Published: December 2021

Background: The relationship between cardiac functions and the fatal outcome of coronavirus disease 2019 (COVID-19) is still largely underestimated. We aim to explore the role of heart failure (HF) and NT-proBNP in the prognosis of critically ill patients with COVID-19 and construct an easy-to-use predictive model using machine learning.

Methods: In this multicenter and prospective study, a total of 1,050 patients with clinical suspicion of COVID-19 were consecutively screened. Finally, 402 laboratory-confirmed critically ill patients with COVID-19 were enrolled. A “triple cut-point” strategy of NT-proBNP was applied to assess the probability of HF. The primary outcome was 30-day all-cause in-hospital death. Prognostic risk factors were analyzed using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression, further formulating a nomogram to predict mortality.

Results: Within a 30-day follow-up, 27.4% of the 402 patients died. The mortality rate of patients with HF likely was significantly higher than that of the patient with gray zone and HF unlikely (40.8% vs. 25 and 16.5%, respectively, P < 0.001). HF likely [Odds ratio (OR) 1.97, 95% CI 1.13–3.42], age (OR 1.04, 95% CI 1.02–1.06), lymphocyte (OR 0.36, 95% CI 0.19–0.68), albumin (OR 0.92, 95% CI 0.87–0.96), and total bilirubin (OR 1.02, 95% CI 1–1.04) were independently associated with the prognosis of critically ill patients with COVID-19. Moreover, a nomogram was developed by bootstrap validation, and C-index was 0.8 (95% CI 0.74–0.86).

Conclusions: This study established a novel nomogram to predict the 30-day all-cause mortality of critically ill patients with COVID-19, highlighting the predominant role of the “triple cut-point” strategy of NT-proBNP, which could assist in risk stratification and improve clinical sequelae.
U-Shaped Association of the Heart Rate Variability Triangular Index and Mortality in Hemodialysis Patients With Atrial Fibrillation
Authors: Braunisch Matthias C. , Mayer Christopher C. , Werfel Stanislas , Bauer Axel , Haller Bernhard , Lorenz Georg , Günthner Roman , Matschkal Julia , Bachmann Quirin , Thunich Stephan , Schlegl Michaela , Ludwig Maximilian , Holzmann-Littig Christopher , Assali Tarek , Pachmann Martin , Küchle Claudius , Renders Lutz , Wassertheurer Siegfried , Müller Alexander , Schmidt Georg , Heemann Uwe , Malik Marek , Schmaderer Christoph
Published: December 2021

Background: Atrial fibrillation (AF) is common in hemodialysis patients and contributes to increased mortality. We aimed to examine heart rate variability triangular index (HRVI) in hemodialysis patients with AF as it has recently been reported to predict mortality in AF patients without kidney disease.

Methods: A total of 88 patients on hemodialysis with a medical history of AF or newly diagnosed AF underwent 24-h electrocardiography recordings. The primary endpoint of cardiovascular mortality was recorded during a median follow up of 3.0 years. Risk prediction was assessed by Cox regression, both unadjusted and adjusted for the Charlson Comorbidity Index and the Cardiovascular Mortality Risk Score.

Results: Median age was 76 years, median dialysis vintage was 27 months. Altogether, 22 and 44 patients died due to cardiovascular and non-cardiovascular causes. In 55% of patients AF was present during the recording. Kaplan-Meier plots of HRVI quartiles suggested a non-linear association between HRVI, cardiovascular, and all-cause mortality which was confirmed in non-linear Cox regression analysis. Adjusted linear Cox regression revealed a hazard ratio of 6.2 (95% CI: 2.1–17.7, p = 0.001) and 2.2 (95% CI: 1.3–3.8, p = 0.002) for the outer quartiles (combined first and fourth quartile) for cardiovascular and all-cause mortality, respectively. Patients in the first quartile were more likely to have sinus rhythm whereas patients in the fourth quartile were more likely to have AF.

Conclusions: We found a U-shaped association between HRVI and mortality in hemodialysis AF patients. The results might contribute to risk stratification independent of known risk scores in hemodialysis AF patients.
Plasma Big Endothelin-1 Level Predicted 5-Year Major Adverse Cardiovascular Events in Patients With Coronary Artery Ectasia
Authors: Cai Zhongxing , Wang Haoyu , Yuan Sheng , Yin Dong , Song Weihua , Dou Kefei
Published: December 2021

Background: Coronary artery ectasia (CAE) is found in about 1% of coronary angiography and is associated with poor clinical outcomes. The prognostic value of plasma big Endothelin-1 (ET-1) in CAE remains unknown.

Methods: Patients with angiographically confirmed CAE from 2009 to 2015, who had big ET-1 data available were included. The primary outcome was 5-year major adverse cardiovascular events (MACE), defined as a component of cardiovascular death and non-fatal myocardial infarction (MI). Patients were divided into high or low big ET-1 groups using a cut-off value of 0.58 pmol/L, according to the receiver operating characteristic curve. Kaplan-Meier method, propensity score method, and Cox regression were used to assess the clinical outcomes in the 2 groups.

Results: A total of 992 patients were included, with 260 in the high big ET-1 group and 732 in the low big ET-1 group. At 5-year follow-up, 57 MACEs were observed. Kaplan-Meier analysis and univariable Cox regression showed that patients with high big ET-1 levels were at increased risk of MACE (9.87 vs. 4.50%; HR 2.23, 95% CI 1.32–3.78, P = 0.003), cardiovascular death (4.01 vs. 1.69%; HR 2.37, 95% CI 1.02–5.48, P = 0.044), and non-fatal MI (6.09 vs. 2.84%; HR 2.17, 95% CI 1.11–4.24, P = 0.023). A higher risk of MACE in the high big ET-1 group was consistent in the propensity score matched cohort and propensity score weighted analysis. In multivariable analysis, a high plasma big ET-1 level was still an independent predictor of MACE (HR 1.82, 95% CI 1.02–3.25, P = 0.043). A combination of high plasma big ET-1 concentrate and diffuse dilation, when used to predict 5-year MACE risk, yielded a C-statistic of 0.67 (95% CI 0.59–0.74).

Conclusion: Among patients with CAE, high plasma big ET-1 level was associated with increased risk of MACE, a finding that could improve risk stratification.
Uncovering the Role of Gut Microbiota in Amino Acid Metabolic Disturbances in Heart Failure Through Metagenomic Analysis
Authors: Hayashi Tomohiro , Yamashita Tomoya , Takahashi Tomoya , Tabata Tokiko , Watanabe Hikaru , Gotoh Yasuhiro , Shinohara Masakazu , Kami Kenjiro , Tanaka Hidekazu , Matsumoto Kensuke , Hayashi Tetsuya , Yamada Takuji , Hirata Ken-ichi
Published: December 2021

Aims: Circulating amino acid (AA) abnormalities serve as predictors of adverse outcomes in patients with heart failure (HF). However, the role of the gut microbiota in AA disturbances remains unknown. Thus, we investigated gut microbial functions and their associations with AA metabolic alterations in patients with HF.

Methods and Results: We performed whole-genome shotgun sequencing of fecal samples and mass spectrometry-based profiling of AAs in patients with compensated HF. Plasma levels of total essential AAs (EAAs) and histidine were significantly lower in patients with HF than in control subjects. HF patients also displayed increased and decreased abundance of gut microbial genes involved in the degradation and biosynthesis, respectively, of EAAs, including branched-chain AAs (BCAAs) and histidine. Importantly, a significant positive correlation was observed between the abundance of microbial genes involved in BCAA biosynthesis and plasma BCAA levels in patients with HF, but not in controls. Moreover, network analysis revealed that the depletion of Eubacterium and Prevotella, which harbor genes for BCAA and histidine biosynthesis, contributed to decreased abundance of microbial genes involved in the biosynthesis of those EAAs in patients with HF.

Conclusions: The present study demonstrated the relationship between gut microbiota and AA metabolic disturbances in patients with HF.
Adaptive On-the-Fly Changes in Distributed Processing Pipelines
Authors: Albers Toon , Lazovik Elena , Hadadian Nejad Yousefi Mostafa , Lazovik Alexander
Published: December 2021

Distributed data processing systems have become the standard means for big data analytics. These systems are based on processing pipelines where operations on data are performed in a chain of consecutive steps. Normally, the operations performed by these pipelines are set at design time, and any changes to their functionality require the applications to be restarted. This is not always acceptable, for example, when we cannot afford downtime or when a long-running calculation would lose significant progress. The introduction of variation points to distributed processing pipelines allows for on-the-fly updating of individual analysis steps. In this paper, we extend such basic variation point functionality to provide fully automated reconfiguration of the processing steps within a running pipeline through an automated planner. We have enabled pipeline modeling through constraints. Based on these constraints, we not only ensure that configurations are compatible with type but also verify that expected pipeline functionality is achieved. Furthermore, automating the reconfiguration process simplifies its use, in turn allowing users with less development experience to make changes. The system can automatically generate and validate pipeline configurations that achieve a specified goal, selecting from operation definitions available at planning time. It then automatically integrates these configurations into the running pipeline. We verify the system through the testing of a proof-of-concept implementation. The proof of concept also shows promising results when reconfiguration is performed frequently.
Link Prediction Between Structured Geopolitical Events: Models and Experiments
Authors: Kejriwal Mayank
Published: December 2021

Often thought of as higher-order entities, events have recently become important subjects of research in the computational sciences, including within complex systems and natural language processing (NLP). One such application is event link prediction. Given an input event, event link prediction is the problem of retrieving a relevant set of events, similar to the problem of retrieving relevant documents on the Web in response to keyword queries. Since geopolitical events have complex semantics, it is an open question as to how to best model and represent events within the framework of event link prediction. In this paper, we formalize the problem and discuss how established representation learning algorithms from the machine learning community could potentially be applied to it. We then conduct a detailed empirical study on the Global Terrorism Database (GTD) using a set of metrics inspired by the information retrieval community. Our results show that, while there is considerable signal in both network-theoretic and text-centric models of the problem, classic text-only models such as bag-of-words prove surprisingly difficult to outperform. Our results establish both a baseline for event link prediction on GTD, and currently outstanding challenges for the research community to tackle in this space.
Improving Dyspnoea Symptom Control of Patients in Palliative Care Using a Smart Patch-A Proof of Concept Study
Authors: Mallick Mostafa Kamal , Biser Sarah , Haridas Aathira , Umesh Vaishnavi , Tönsing Olaf , Yari Imrana Abdullahi , Ollenschläger Malte , Heckel Maria , Ostgathe Christoph , Kluge Felix , Eskofier Bjoern , Steigleder Tobias
Published: December 2021

The world of healthcare constantly aims to improve the lives of people while nurturing their health and comfort. Digital health and wearable technologies are aimed at making this possible. However, there are numerous factors that need to be addressed such as aging, disabilities, and health hazards. These factors are intensified in palliative care (PC) patients and limited hospital capacities make it challenging for health care providers (HCP) to handle the crisis. One of the most common symptoms reported by PC patients with severe conditions is dyspnoea. Monitoring devices with sufficient comfort could improve symptom control of patients with dyspnoea in PC. In this article, we discuss the proof-of-concept study to investigate a smart patch (SP), which monitors the pulmonary parameters: (a) breathing rate (BR) and inspiration to expiration ratio (I:E); markers for distress: (b) heart rate (HR) and heart rate variability (HRV), and (c) transmits real-time data securely to an adaptable user interface, primarily geared for palliative HCP but scalable to specific needs. The concept is verified by measuring and analyzing physiological signals from different electrode positions on the chest and comparing the results achieved with the gold standard Task Force Monitor (TFM).
Diverse Inter-Annual Variations of Winter Siberian High and Link With Eurasian Snow in Observation and BCC-CSM2-MR Coupled Model Simulation
Authors: Sun Chenghu , Zuo Jinqing , Shi Xiaohui , Liu Xiangwen , Liu Haiwen
Published: December 2021

An observational study illustrates that three distinct modes of winter Siberian high variability exist in observations at the inter-annual time scale. In this paper, we compare the connection between these diverse Siberian high variation modes with pre-autumn and simultaneous Eurasian snow cover in an observation and BCC-CSM2-MR coupled climate model run under pre-industrial conditions from the CMIP6 project. Our analyses indicate that the inter-annual variation of observed Siberian high modes do have a connection with pre-autumn and simultaneous Eurasian snow cover anomalies, but the BCC-CSM2-MR coupled climate model does not capture the observed diverse Eurasian snow–Siberian high relationships well. The BCC-CSM2-MR coupled climate model can partly reproduce the observed Siberian high variation modes, but fail to capture the spatial distribution and statistics of boreal fall and winter Eurasian snowpack, which is a key facet of simulated diverse Siberian high variability irrespective of the influence of Eurasian snow cover.
Study on Production Optimization Method of Fractured Reservoir Based on Connectivity Model
Authors: Li Dajian , Zhao Zhenfeng , Wang Bai , Yang Haitao , Cui Wenhao , Ruan Jiayu , Zhang Yuxin , Wang Fan
Published: December 2021

Due to the extensive development of fractures and serious heterogeneity in fractured reservoirs, it is difficult for the traditional numerical simulation method to invert its geology, which greatly limits the efficiency and accuracy of simulation and cannot realize the real-time optimization of production scheme. The connectivity model can only consider the two characteristic parameters of conductivity and connectivity volume, which does not involve complex and rigorous geological modeling. It can quickly and accurately reflect the state of the real reservoir, greatly reducing the simulation time, and is suitable for real-time production performance prediction of the reservoir. Due to the large difference in conductivity of fractured reservoirs, the difficulty of fitting increases. In this paper, the connectivity model is first applied to fractured reservoirs to realize the production dynamic simulation of fractured reservoirs. The optimization principle is used to optimize the injection-production scheme with the economic net present value as the objective function. In order to verify the method, the connectivity model is applied to Mu 30 of Changqing Oilfield in this paper. The results show that this method can effectively reflect the real production situation of the oilfield and the connectivity of the reservoir, and the simulation time is relatively fast. After optimization, the cumulative oil production of the reservoir increases by 8.1%, the cumulative water injection decreases by 2.3%, and the rising rate of water cut decreases by 58.8%, indicating that the connectivity model can realize the real-time production optimization of the reservoir.