bluuebunny/crossref_metadata_2025 huggingface dataset:
Fall Detection using Sensors on a Smartphone
Authors: Priswanto Budi , Haryono Haryono
Published: April 2022

A work accident on a technician causes injury. When doing work, even though the technician is equipped with work safety, there are still factors that can cause accidents intentionally or unintentionally. The development of technology is now more advanced. Now the industrial revolution has reached the era of 4.0. Its progress is accompanied by information technology that is growing very rapidly. Many internets of things devices can already be used in everyday life. In today's life, the use of IoT devices has become a habit of today's modern society. For example, to travel using public transportation, there are many mobile apps that are connected to transportation providers. Including trade, the number of marketplaces has caused the growth of smartphones to be very fast. Smartphones are now equipped with many sensors, ranging from GPS sensors, wi-fi sensors, temperature sensors, and various sensors. Often the technicians in charge of climbing towers or heights are never caught by management or project leaders. Even though this causes losses both losses for technicians and losses for management. Therefore, how to monitor the technicians to be careful in carrying out their duties. Android smartphone devices have many sensors. Sensors in Android are used as a fall detection tool. By using Android sensors, the use of Internet of Thing sensors on smartphones will produce very useful monitoring tools. The use of Flutter framework as a medium for utilizing the accelerometer sensor and gyroscope sensor as a fall detection tool. This study aims to create a prototype of a fall detection application system.
Empoderamento da gestante contra a violência obstétrica
Authors: Souza Tainá Pereira e , Santos Maria Victória de Almeida , Corgozinho Viviane Aparecida , Oliveira Maila Martins , Almeida Camila Souza de , Souza Débora Aparecida Silva
Published: April 2022

Objetivo: descrever as estratégias educativas para o empoderamento da gestante na prevenção da violência obstétrica. Método: revisão integrativa da literatura estruturada em seis etapas guiadas pelo checklist Preferred eporting Itens for Systematic Reviews and Meta-Analyses. As bases de dados utilizadas foram Literatura Latino-Americana e do Caribe em Ciências da Saúde, Sistema Online de Busca e Análise de Literatura Médica, Banco de Dados em Enfermagem, INDEX Psicologia e o Índice Bibliográfico Español em Ciencias de La Salud. Resultados: a amostra final totalizou onze artigos que consideraram as rodas de conversa, adesão ao pré-natal, educação permanente para a equipe multiprofissional, uso de material de apoio e utilização da rede cegonha como abordagens importantes para realizar a educação em saúde para o empoderamento de gestantes na prevenção da violência obstétrica. Conclusão: estratégias educativas realizadas no pré-natal promove o empoderamento das gestantes a partir do desenvolvimento da sua autonomia nas tomadas de decisões sobre o parto prevenindo situações de violência obstétrica.
Therapeutic schemes of denosumab in the treatment of giant cell tumor of bone - Protocol for a systematic review with meta-analysis
Authors: Barreto Bruno Garcia , Santili Cláudio , Guedes Alex , Paz Cláudio Luiz da Silva Lima , Moreira Fernando Delmonte , Mattos Enilton Santana Ribeiro de
Published: April 2022

The aim of this study is to evaluate the efficacy of different therapeutic regimens using denosumab in patients with giant cell tumor of bone (GCTB), regarding primary outcomes related to therapeutic response (lesion size, pain and function) and presentation to imaging exams, in addition to secondary outcomes related to age (in years) and tumor location, reduction or downgrade of surgical indication, local recurrence, presence of pulmonary metastases and therapeutic side effects. A systematic literature search will be carried out in the PubMed/MEDLINE, Embase (CAPES Journals), Science Direct/Elsevier, Scielo, Cochrane Library and clinical trial records (ClinicalTrials.gov and Registro Brasileiro de Ensaios Clínicos) databases; for exploration of grey literature, the Open Access Theses and Dissertations and the Biblioteca Digital Brasileira de Teses e Dissertações databases will be consulted. We will also conduct a "snowball" survey to identify additional eligible studies for full-text review. Two evaluators will select, extract and assess the risk of bias of the obtained data. If appropriate, a meta-analysis will be carried out, extracting data for the number of events and total patients to perform proportion meta-analysis using the R software, with the "meta" package (version 4.9–6), the "metaprop function" for aspect ratio data. The results of this review will provide convincing information on the efficacy of different therapeutic regimens using denosumab in GCTB, providing a reliable theoretical basis for the research that will follow.
Genetic variation in wood properties of mid-rotation age Eucalyptus globoidea
Authors: Iyiola Ebenezer A. , Altaner Clemens M. , Apiolaza Luis A.
Published: April 2022

Background: Eucalyptus globoidea Blakely produces ground-durable (Class 2) and stiff wood and has the potential to be grown in New Zealand to supply high-value environmentally-friendly timber for use as posts in the agricultural sector and stiff veneers for the LVL industry. The New Zealand Dryland Forests Initiative (NZDFI) has established a breeding programme for this species. The objective of this study was to identify trees with superior wood properties for commercial propagation enabling the establishment of a domestic plantation resource of ground-durable timber. Methods: The genetic variation in wood properties at mid-rotation age (8-year-old) of 141 E. globoidea families was assessed for the following traits: heartwood diameter, diameter under bark at ~0.5 m height, combined sapwood diameter, heartwood collapse, sapwood collapse, standing tree acoustic velocity and extractive content in the heartwood. Families were ranked and genotypes with large heartwood diameter, high extractive content and stiffness as well as low collapse were identified. Results: Heartwood diameter (h2 = 0.51) and extractive content (h2 = 1.16) showed good heritability, which in combination with high variation are promising traits for a breeding programme. The high heritability for extractive content indicated a closer relatedness within the population than the assumption of unrelated families of half-siblings. The unfavourable correlation between the heartwood diameter and extractive content (genetic correlation (rg) = −0.45) indicated that a compromise is required for simultaneous improvement of both traits. Heritability estimates for heartwood collapse (h2 = 0.30) and acoustic velocity (h2 = 0.36) were moderate. Conclusions: Genetic selection for wood quality traits of E. globoidea is practically feasible. Superior individuals with above average performance for multiple traits were present in the breeding populations, however, this was dependent on the intended end use of the timber.
Algal flora Saint-Petersburg water bodies
Authors: Balashova Nataliya B. , Kiselev Grigorii A.
Published: April 2022

In the spring and summer of 2019, 43 lakes and ponds of Saint Petersburg were surveyed. The algal flora contains 110 species of algae of the following divisions: Cyanophyta =Cyanobacteria=Cyanoprokaryota – 18, Cryptophyta – 1, Dinophyta – 9, Euglenophyta – 11, Chlorophyta – 57 Streptophyta - 2, Ochrophyta (classes Chrysophyceae – 2, Bacillariophyceae – 10). For the majority of the found species, the saprobity mark and saprobic index were specified. The most diverse group in the water bodies of Saint Petersburg is green algae, which includes single and coenobial algae of the coccoid and monad tallom organization, which are well adapted to vegetation in the water column. In most reservoirs at spring Monoraphidium arcuatum (Korshikov) Hindák and Monoraphidium contortum (Thuret) Komárkova-Legnerova, species of genera Scenedesmus, including species of the genera Desmodesmus and Tetradesmus actively vegetate. In the reservoirs of Saint Petersburg, the leading positions are taken by euglenic algae, especially species of genera Trachelomonas (Trachelomonas hispida (Perty) F. Stein, Trachelomonas volvocina (Ehrenberg) Ehrenberg). Summer phytoplankton differs in the more vigorous development of blue-green algae-especially such species as Dolichospermum flosaquae (Brébisson ex Bornet & Flahault) P. Wacklin, L. Hoffmann & Komárek, Dolichospermum spiroides (Klebhan) Wacklin, L. Hoffmann & Komárek. The species of β- mesosaprobic dominate. There are also α-mesosaprobes and species with a wide range of existence in reservoirs with different degrees of organic content. Biological analysis of the surveyed water bodies shows that their condition is satisfactory.
The current state of the population of the rare species Chara strigosa A. Braun in the Nizhny Novgorod region
Authors: Biryukova Olga V. , Schestakova Anna A. , Vishnyakov Vasily S. , Belyakov Eugeny A.
Published: April 2022

The information about the habitats of the rare relict species Chara strigosa A. Braun is updated. The data on the state of the population and the phytocenotic role of the species in the composition of the vegetation coverof lakes are presented.
Study of the algae flora of the Orenburg region: history and modernity
Authors: Ignatenko Marina E. , Yatsenko-Stepanova Tatyana N.
Published: April 2022

The article deals with the history of studying the species richness of algae in the Orenburg region from the first publications of the early nineteenth century to the present.
The Influence of Thematic Monopoly Media on Learning Outcomes on The Theme of Technology Development of Third Grade
Authors: Ayunin Qurrota , Siswanto M. Bambang Edi
Published: April 2022

This study discusses thematic monopoly media on learning outcomes on the theme of third grade technology development at SD Islam Al Washoya Jombang which aims (1) To determine learning outcomes in the theme of technology development for third grade students at SD Islam Al Washoya without using thematic monopoly media. (2) To find out the learning outcomes in the theme of technology development of third grade students of Al Washoya Islamic Elementary School by using thematic monopoly media. (3) To find out there is a difference in the average thematic learning outcomes between students who learn to use thematic monopoly media and students who study without using monopoly media for class III Al Washoya Islamic Elementary School. In this study, the type of research was "Quasy Experiment" using a "non-equivalent control group design" design. The population of this research is all third grade students of Al Washoya Islamic Elementary School which has a total of 16 students. The sample used is class III students who have a total of 16 students, namely 8 students as the control class and 8 students as the experimental class. Based on the results of the descriptive analysis, the average value of the two groups was obtained, namely the control class with a pretest score of 68.13 and a post-test score of 66.88, while in the experimental class the pretest score was 66.88 and the posttest score was 91.88. The results of inferential statistical analysis obtained the value of Sig. (2-tailed) < or (0.000 < 0.05). Thus, it can be concluded that there is a difference in the average learning outcomes of third grade students of SD Islam Al Washoya who are taught to use thematic monopoly media and those who are not taught to use thematic monopoly media.
Development of Puzzle Learning Media to Introduce the Types of Animals Based on Their Breeding Methods in Grade 3 Students at SDN Catakgayam 1
Authors: Muna Lailatul , Nuruddin Muhammad
Published: April 2022

Success in learning depends on the skills of teachers who manage learning activities. There is a new syllabus in the world of Indonesian education, namely thematic. Thematic is a learning method that presents various lessons into a subject that has a subject process with one theme and is adapted to student development (Diani, 2017: 105). Therefore, when using thematic applied teaching in primary schools, teachers should use tools to provide a variety of teaching materials. However, SDN Catak Gayam 1 Mojowarno in its teaching staff is still not varied when teaching during the pandemic. The purpose of this study was to develop a puzzle learning media to introduce the types of animals based on their breeding methods. This type of research is research and development using 4D models. The data was obtained by using a questionnaire/questionnaire and the observation of the research results produced a product in the form of puzzle learning media. The eligibility of puzzle media is included in the criteria, with an average score or score 91% and the effectiveness of the puzzle media can be seen from the results of the observation sheet during learning which is assessed by the class teacher and gets a percentage of 88% containing the very effective category.
Establishment of Discipline Character Through PKn Materials on Class V Students of SDN Gelaran 2
Authors: Rohmah Fitria Ani , Raharja Hawwin Fitra
Published: April 2022

Charakter training right now is extremely fundamental, on the grounds that as of now the Indonesian country is encountering a person emergency in the country's kids. As far as what is implied by character is the person, character, ethics, or character in an individual that is shaped from the consequences of encouraging different excellencies that have been accepted and utilized as a reason for viewpoint, think, act, and act. This study utilizes a subjective exploration approach and the kind of spellbinding subjective examination. Information were gathered utilizing perception, meetings, and documentation techniques. The targets of this study are (1) to depict the development of disciplinary person in students through Civics subjects for class V SDN Gelaran 2, (2) To describe Civics subjects can shape the discipline character of students in class V at SDN Gelaran 2. The results of this study are (1) The formation of a disciplined character in students through Civics Class V subjects at SDN Gelaran 2 is realized through material understanding the rights, obligations and responsibilities as citizens in everyday life and the teacher also always provides confirmation of the values of disciplined character and ethics or good morals such as showing discipline in the process of learning activities, both time discipline, discipline in doing assignments, and discipline in the classroom, one of which is creating a conducive atmosphere, focusing on lessons, and then the teacher also always sets an example of being disciplined to students , (2) very good for students, students can not violating school rules, wearing uniforms in accordance with school regulations, not being late for school, listening to explanations from teachers when learning activities are in progress, carrying out class picket assignments and not disturbing friends while teaching and learning activities.
Forming The Disciplined Characters for Grade 2A Students of SDN Bareng III Through Online Learning Models
Authors: Hasanah Irodatul , Yunita Rahma Pratiwi Emy
Published: April 2022

Condition of the world that is currently uncertain due to the pandemic means engulfing both the world community in general and Indonesian people in particular. This is also very influential on the teaching and learning process in Indonesia. The thing that is considered more important during online learning is the formation of a disciplined character that must be instilled students under any conditions. In order for learning activities to continue, learning is carried out using online learning models in an effort to form a disciplined character in students during the Covid-19 pandemic. This research is a qualitative descriptive study that aims to describe (1) the online learning process, (2) learning method. (3) role of parents, (4) advantages and disadvantages, in forming the disciplined character of grade 2 A students at SDN Bareng III. The method used in this study is a descriptive qualitative method which implies that the research is carried out in natural conditions. Based on the findings, it can be described as follows: (1) The teaching and learning process is using an online learning model. (2) The learning method used assignment and some materials as well as the cultivation of disciplined characters are carried out by using learning media in the form of videos and pictures. (3) The role of parents is considered very important. (4) The advantage that students understand rules that exist in house, while the disadvantage is that students cannot divide time between learning and playing.
Development of The Thematic Module Based on Local Wisdom of Jombang Regency on The Uniqueness of The Sub-theme of The Area I Live in
Authors: Kulsum Umaiyah Binti Umi , Asmarani Ratih
Published: April 2022

The direction of the showing modelals involved by instructors in grade IV at the State Primary School Title II Bareng, Jombang Regime is an administration distributed book comprising of topical pack book, the learning of which has not zeroed in on the attributes, needs and living climate of understudies, particularly understudies. who lives in Jombang Rule. This innovative work expects to create a topical module for grade IV Primary School in sub-subject 2 of the uniqueness of the area where I reside in light of neighborhood intelligence of Jombang Rule which is substantial and possible to utilize. This innovative work utilizes the ADDIE model. Wellsprings of information from the module advancement process are acquired from portrayals of exercises and consequences of exercises beginning from the investigation stage to the assessment stage. The wellspring of information from the nature of the module is acquired from the evaluation of modelal specialists and media specialists, clients (instructors), and understudy reactions. This innovative work is completed in the levels semester of the 2020/2021 scholastic year. This innovative work was brought out through 5 phases, specifically the investigation stage, the plan stage, the advancement stage, the execution stage, and the assessment stage. The aftereffects of this innovative work were gotten (1) The consequences of the approval of the achievability of the module from the modelal master acquired a rate score of 95% the rules were exceptionally substantial and appropriate for use. Approval of media specialists got a rate score of 93.3% exceptionally legitimate standards and practical to utilize. (2) The aftereffects of the execution of the topical module in view of neighborhood shrewdness in Jombang Rule were done utilizing an educator and understudy reaction poll. The instructor's reaction survey acquired a worth of 93.3% awesome models and doable to utilize. The understudy reaction survey got a score of 90% with awesome rules and should be utilized. The normal evaluation of modelal specialists, media specialists and clients (reaction of instructors and understudies) is 93%. Alluding to the score understanding standards, the Topical Module for Grade IV Primary School in Sub-subject 2 "The Uniqueness of the Area I Live" In light of Neighborhood Astuteness in Jombang Rule has met the models of being exceptionally legitimate and reasonable for use.
The Effect of Pop Up Book Media on Mathematics Learning Outcomes in Building Space Materials on Class II
Authors: Imroatus Solikhah Alfi , Edi Siswanto M. Bambang
Published: April 2022

The reason for this review is to add knowledge into the consequences of the pretest and post-test when and without the utilization of learning media as Pop Up Books on learning results of Mathematics, the impact of utilizing Pop Up Book media on understudy learning results. exploration is Pre-Experimental Design. This examination was led at SDN Kampungbaru III. The example in this review comprised of one class of 17 understudies. Into two gatherings where the principal meeting understudies are given learning not utilizing spring up book media or customary strategies while at the second gathering understudies are surrendered getting the hang of utilizing pop book media. Information examination strategies include: (1) Normality Test and (2) Hypothesis Testing or T Test, information investigation utilizing clear investigation and inferential factual examination with PC help with the Statistical Package for Social Science (SPSS) adaptation 17.0 program. The consequences of the review can be reasoned that The capacity to comprehend understudies' spatial development material in the wake of utilizing spring up book media in class II SD Negeri Kampungbaru III understudies is sorted as fit, this is confirmed by the normal score acquired by understudies contacting the number 87-94 and the impact of learning Mathematics on the material of class II SD Negeri Kampungbaru III shows that there is a huge contrast of 0.000 which is more modest than the 0.05 importance (0.000 < 0.05), so the speculation (H) in this review is announced acknowledged.
E-learning From Faculty Members’ Perspectives
Authors: Zomrawi Nagi , Omer Emadeldin
Published: April 2022

Face-to-face conventional learning is the dominant method of education all over the world. But the Covid-19 pandemic opens the way for e-learning to take an unexpected wide trial chance to grow and take place in a short period. This study research targeted and concentrated on English language faculty members who are presenting the preparatory-year English language courses delivered by the deanship of the preparatory year. Results reflected that all English language faculty members have a positive perspective towards e-learning, regarding skills and experience, self and student efficiency, and enjoyment, but some of them face technical problems in dealing with the e-learning management system concerned with adding academic materials making tests, etc. but when these problems are solved for them, they look with favor on e-learning. Also, the complication of deceit prevention during online assessments represents one of the faculty members’ worries.
Jet-Grouting Technology for Reinforcement Strata Disturbance After Sand Mining
Authors: Fu Tao , Wang Kai , Ren Xiaoqian , Zhu Zhixin , Wang Liang
Published: April 2022

During the construction of a bridge, due to the deep sand mining in the riverbed at the bridge site, a sand mining disturbance stratum is formed at the bridge site, and it has an impact on the construction quality of the pile group foundation. In this paper, in view of the special geological conditions caused by sand mining, the high-pressure jet grouting method was used to reinforce the disturbed stratum at the bridge site, and a scheme and key construction technology high-pressure rotary jet pile grouting to reinforce the disturbed stratum caused by sand mining is proposed. A three-dimensional finite element model of the pile group before and after reinforcement of the disturbed stratum by high-pressure jet grouting method is established. The distribution characteristics of the lateral displacement of the borehole wall in the disturbed stratum before and after reinforcement are compared and analysed. Application on an actual bridge proves that the high-pressure jet grouting method has a good reinforcement effect on the disturbed stratum, which effectively solves the phenomenon of hole expansion and pile casing falling in the construction process of the pile foundation caused by sand mining disturbance and improves the working performance and construction quality of the pile group foundation. The high-pressure jet grouting technique for reinforcement of disturbed stratum is proved to be effective in practice.
Time-Course Transcriptome Analysis of Lungs From Mice Infected With Hypervirulent Klebsiella pneumoniae via Aerosolized Intratracheal Inoculation
Authors: Zheng Xinying , Guo Jianshu , Cao Chaoyue , Qin Tongtong , Zhao Yue , Song Xiaolin , Lv Meng , Hu Lingfei , Zhang Lili , Zhou Dongsheng , Fang Tongyu , Yang Wenhui
Published: April 2022

HypervirulentKlebsiella pneumoniae(hvKp) can cause life-threatening community-acquired infections among healthy young individuals and is thus of concern for global dissemination. In this study, a mouse model of acute primary hvKp pneumonia was establishedviaaerosolized intratracheal (i.t.) inoculation, laying the foundation for conducting extensive studies related to hvKp. Subsequently, a time-course transcriptional profile was created of the lungs from the mouse model at 0, 12, 24, 48 and 60 hours post-infection (hpi) using RNA Sequencing (RNA-Seq). RNA-Seq data were analyzed with the use of Mfuzz time clustering, weighted gene co-expression network analysis (WGCNA) and Immune Cell Abundance Identifier for mouse (ImmuCellAI-mouse). A gradual change in the transcriptional profile of the lungs was observed that reflected expected disease progression. At 12 hpi, genes related to acute phase inflammatory response increased in expression and lipid metabolism appeared to have a pro-inflammatory effect. At 24 hpi, exacerbation of inflammation was observed and active IFN-γ suggested that signaling promoted activation and recruitment of macrophages occurred. Genes related to maintaining the structural integrity of lung tissues showed a sustained decrease in expression after infection and the decrease was especially marked at 48 hpi. TNF, IL-17, MAPK and NF-kB signaling pathways may play key roles in the immunopathogenesis mechanism at all stages of infection. Natural killer (NK) cells consistently decreased in abundance after infection, which has rarely been reported in hvKp infection and could provide a new target for treatment. GenesSaa1andSlpiwere significantly upregulated during infection. BothSaa1, which is associated with lipopolysaccharide (LPS) that elicits host inflammatory response, andSlpi, which encodes an antimicrobial protein, have not previously been reported in hvKp infections and could be important targets for subsequent studies. To t our knowledge, this paper represents the first study to investigate the pulmonary transcriptional response to hvKp infection. The results provide new insights into the molecular mechanisms underlying the pathogenesis of hvKp pulmonary infection that can contribute to the development of therapies to reduce hvKp pneumonia.
Cryoballoon Ablation for Treatment of Atrial Fibrillation in a Chinese Population: Five-Year Outcomes and Predictors of Recurrence After a Single Procedure
Authors: Chen Xiongbiao , Xia Yu , Lin Yuan , Li Xiaofeng , Wang Chun , Chen Yanjun , Fang Pihua , Liu Jun
Published: April 2022

Background

The 5-year outcomes and predictors of atrial fibrillation (AF) recurrence following cryoballoon (CB) ablation in Chinese population remain scarce. Our aim was to report 5-year outcomes and predictors of AF recurrence following a single CB ablation procedure in a Chinese population.

Methods

From December 2013 to August 2016, we included 256 consecutive patients (mean age: 58 ± 10.9 years old; female: 41.0%) with paroxysmal or persistent AF successfully underwent first-generation CB ablation at Fuwai hospital in this prospective study. All patients were followed at least 5 years or when there was recurrent AF. Independent predictors of AF recurrence were determined by Cox proportional hazards regression analysis.

Results

The 5-year success rate after pulmonary vein isolation (PVI) by a single procedure was 59.4%. The recurrence rate was the highest (14.5%) within the first year after the index procedure, and then stabilized. Patients with paroxysmal AF had a higher incidence of freedom from AF recurrence than patients with persistent AF (63.2% vs. 36.4%, log-rank P < 0.01). The overall incidence of complications related to CB ablation was 7.8%. Phrenic nerve injury (PNI) was the most common complication, with an incidence of 3.5%, and patients with PNI were recovered within the 1-year follow-up. Only persistent AF (HR 1.72, 95%CI 1.028–2.854, P < 0.05) was significantly and independently associated with an increased risk of AF recurrence after adjusting for other factors.

Conclusion

Pulmonary vein isolation using CB ablation was safe and effective with an acceptable complication and 5-year success rate in a Chinese population with AF, and persistent AF was the independent predictor for 5-year AF recurrence after a single CB ablation procedure.
Efficacy of INtensive Treatment vs. Standard Treatment of COmpound DanshEn Dripping Pills in Refractory Angina Patients With Incomplete Revascularization (INCODER Study): Study Protocol for a Multicenter, Double-Blind, Randomized Controlled, Superiority Trial
Authors: Wu Zexuan , Xu Danping , Wu Zhen , Chen Ailan , Liu Lijuan , Ling Li , Zhou Yan , Liu Duoduo , Liu Yin , Dong Yugang , Chen Yili
Published: April 2022

Introduction

Patients with incomplete revascularization (ICR) tend to develop refractory angina despite optimal medical therapy. The Compound Danshen Dripping Pills (CDDP) is a widely used antianginal drug in China and is shown to significantly alleviate myocardial ischemia. Previous studies showed dose-efficacy tendency when increasing doses of CDDP. This study aims to investigate the efficacy and safety of intensive doses of CDDP in patients with refractory angina with ICR.

Methods and Analysis

The INCODER study is a multicenter, double-blind, randomized controlled, superiority trial. We plan to recruit 250 patients aged 18–85 years with a diagnosis of refractory angina with ICR. Patients will be randomized (1:1) to intensive treatment group (CDDP 20 pills three times per day) or standard treatment group (10 pills CDDP and 10 pills placebo three times per day). Patients will have a 6-week medication period and be followed up every 2 weeks. The primary endpoint is the change of total exercise time from baseline to week 6 as assessed by cardiopulmonary exercise testing (CPET). Secondary endpoints include changes in the frequency of angina, Canadian Cardiovascular Society angina class, nitroglycerin use, Seattle Angina Questionnaire scores, peak oxygen uptake (VO2 peak) and other parameters as measured by CPET, and the levels of plasma C-reactive protein, homocysteine, and N-terminal pro-B-type natriuretic peptide. Safety events related to CDDP use will be monitored.

Ethics and Dissemination

The research had been approved by the Clinical research and laboratory animal ethics committee of the First Affiliated Hospital, Sun Yat-sen University ([2019]65). The results will be reported through peer-reviewed journals, seminars, and conference presentations.

Trial Registration Number

www.chictr.org.cn (ChiCTR2000032384). Registered on 27 April 2020.
Exploring Key Genes to Construct a Diagnosis Model of Dilated Cardiomyopathy
Authors: Zheng Youyang , Liu Zaoqu , Yang Xinyue , Weng Siyuan , Xu Hui , Guo Chunguang , Xing Zhe , Liu Long , Wang Libo , Dang Qin , Qiu Chunguang
Published: April 2022

Background

Dilated cardiomyopathy (DCM) is characterized by left ventricular dilatation and systolic dysfunction. The pathogenesis and etiologies of DCM remain elusive. This study aims to identify the key genes to construct a genetic diagnosis model of DCM.

Methods

A total of 257 DCM samples from five independent cohorts were enrolled. The Weighted Gene Co-Expression Network Analysis (WGCNA) was performed to identify the key modules associated with DCM. The latent mechanisms and protein-protein interaction network underlying the key modules were further revealed. Subsequently, we developed and validated a LASSO diagnostic model in five independent cohorts.

Results

Two key modules were identified using WGCNA. Novel mechanisms related to the extracellular, mitochondrial matrix or IL-17 signaling pathway were pinpointed, which might significantly influence DCM. Besides, 23 key genes were screened out by combining WGCNA and differential expression analysis. Based on the key genes, a genetic diagnosis model was constructed and validated using five cohorts with excellent AUCs (0.975, 0.954, 0.722, 0.850, 0.988). Finally, significant differences in immune infiltration were observed between the two groups divided by the diagnostic model.

Conclusion

Our study revealed several novel pathways and key genes to provide potential targets and biomarkers for DCM treatment. A key genes’ diagnosis model was built to offer a new tool for diagnosing DCM.
Bayesian Joint Modeling of Multivariate Longitudinal and Survival Data With an Application to Diabetes Study
Authors: Huang Yangxin , Chen Jiaqing , Xu Lan , Tang Nian-Sheng
Published: April 2022

Joint models of longitudinal and time-to-event data have received a lot of attention in epidemiological and clinical research under a linear mixed-effects model with the normal assumption for a single longitudinal outcome and Cox proportional hazards model. However, those model-based analyses may not provide robust inference when longitudinal measurements exhibit skewness and/or heavy tails. In addition, the data collected are often featured by multivariate longitudinal outcomes which are significantly correlated, and ignoring their correlation may lead to biased estimation. Under the umbrella of Bayesian inference, this article introduces multivariate joint (MVJ) models with a skewed distribution for multiple longitudinal exposures in an attempt to cope with correlated multiple longitudinal outcomes, adjust departures from normality, and tailor linkage in specifying a time-to-event process. We develop a Bayesian joint modeling approach to MVJ models that couples a multivariate linear mixed-effects (MLME) model with the skew-normal (SN) distribution and a Cox proportional hazards model. Our proposed models and method are evaluated by simulation studies and are applied to a real example from a diabetes study.
How Can We Reap Learning Benefits for Individuals With Growth and Fixed Mindsets?: Understanding Self-Reflection and Self-Compassion as the Psychological Pathways to Maximize Positive Learning Outcomes
Authors: Kwan Letty Y. -Y. , Hung Yu Sheng , Lam Lam
Published: April 2022

Having a growth mindset has been hailed as one of the most critical advancements in understanding students’ motivation in recent years. The attention on the growth mindset indicates an increased surge in the public’s interest in using evidence-based intervention models to facilitate learning. Because the positive benefits of growth mindsets are apparent, changing ones’ mindset becomes the core focus of growth mindset literature. But aside from “changing” students’ mindsets, finding the right kind of psychological interventions that leverage student’s growth or fixed mindset with sustainable improvement for students can be as, if not more important. The current study seeks to fill this research gap. Our first study indicated that learners with a relatively high growth mindset benefit from a self-reflection learning strategy. However, this very same self-reflection strategy can harm the learning benefits for those learners with a fixed mindset. The second study used experimental manipulation to show that learners with a growth mindset can enhance their learning process and outcomes from self-reflection strategies. In contrast, learners with a fixed mindset can improve their learning process and result from self-compassion strategies. The current study identified two distinct psychological mechanisms – self-reflection and self-compassion and linked them with mindsets with the learning process and learning outcomes. It also demonstrates how learners with growth and fixed mindsets can directly benefit from these two psychological mechanisms in an experimental design.
Gender- and Age-Associated Differences in Bone Marrow Adipose Tissue and Bone Marrow Fat Unsaturation Throughout the Skeleton, Quantified Using Chemical Shift Encoding-Based Water–Fat MRI
Authors: Beekman Kerensa M. , Regenboog Martine , Nederveen Aart J. , Bravenboer Nathalie , den Heijer Martin , Bisschop Peter H. , Hollak Carla E. , Akkerman Erik M. , Maas Mario
Published: April 2022

Bone marrow adipose tissue (BMAT) is a dynamic tissue which is associated with osteoporosis, bone metastasis, and primary bone tumors. The aim of this study is to determine region-specific variations and age- and gender-specific differences in BMAT and BMAT composition in healthy subjects. In this cross-sectional study, we included 40 healthy subjects (26 male: mean age 49 years, range 22–75 years; 14 female: mean age 50 years, range 29–71) and determined the bone marrow signal fat fraction and bone marrow unsaturation in the spine (C3-L5), pelvis, femora, and tibiae using chemical shift encoding-based water–fat imaging (WFI) with multiple gradient echoes (mGRE). Regions of interest covered the individual vertebral bodies, pelvis and proximal epimetaphysis, diaphysis, and distal epimetaphysis of the femur and tibia. The spinal fat fraction increased from cervical to lumbar vertebral bodies (mean fat fraction ( ± SD or (IQR): cervical spine 0.37 ± 0.1; thoracic spine 0.41 ± 0.08. lumbar spine 0.46 ± 0.01; p < 0.001). The femoral fat fraction increased from proximal to distal (proximal 0.78 ± 0.09; diaphysis 0.86 (0.15); distal 0.93 ± 0.02; p < 0.001), while within the tibia the fat fraction decreased from proximal to distal (proximal 0.92 ± 0.01; diaphysis 0.91 (0.02); distal 0.90 ± 0.01; p < 0.001). In female subjects, age was associated with fat fraction in the spine, pelvis, and proximal femur (ρ = 0.88 p < 0.001; ρ = 0.87 p < 0.001; ρ = 0.63 p = 0.02; ρ = 0.74 p = 0.002, respectively), while in male subjects age was only associated with spinal fat fraction (ρ = 0.40 p = 0.04). Fat fraction and unsaturation were negatively associated within the spine (r = -0.40 p = 0.01), while in the extremities fat fraction and unsaturation were positively associated (distal femur: r = 0.42 p = 0.01; proximal tibia: r = 0.47, p = 0.002; distal tibia: r = 0.35 p = 0.03), both independent of age and gender. In conclusion, we confirm the distinct, age- and gender-dependent, distribution of BMAT throughout the human skeleton and we show that, contradicting previous animal studies, bone marrow unsaturation in human subjects is highest within the axial skeleton compared to the appendicular skeleton. Furthermore, we show that BMAT unsaturation was negatively correlated with BMAT within the spine, while in the appendicular skeleton, BMAT and BMAT unsaturation were positively associated.
Effect of Digital Financial Inclusion on Dredging the Path of Green Growth—New Evidence From Front-End and Back-End Perspectives
Authors: Cao Jianhong , Law Siong Hook , Wu Desheng , Tang Xianghua , Yang Xiaodong
Published: April 2022

To dredge China’s green growth path, this paper analyzes the front-end and back-end factors affecting green growth and also investigates the mediation role of digital financial inclusion from different dimensions. This study employs China’s provincial panel data in 2011–2018 and uses the dynamic threshold model to study the threshold effect of technological progress (TP) on green growth (GG) and the threshold effect of green growth (GG) on floating population (FP). The empirical results show that: first, with the digital financial inclusion as the threshold variable, there is a nonlinear relationship between technological progress (TP) and green growth (GG); second, with digital financial inclusion as the threshold variable, there is a nonlinear relationship between green growth (GG) and floating population (FP); third, output biased technological progress needs more support from digital financial inclusion than input biased technological progress than can significantly promote green growth. From the dimension of “digitization+financial scale+inclusion” digital financial inclusion not only improves the positive effect of technological progress on green growth but also alleviates the negative effect of green growth on the floating population. This study makes up for the research gap in the back-end impact of green growth based on new ideas of digital financial inclusion and floating population and has important theoretical reference significance for removing the obstacles in the green development path and realizing sustainable green growth.
Familial Hypercholesterolemia and Elevated Lipoprotein(a): Cascade Testing and Other Implications for Contextual Models of Care
Authors: Loh Wann Jia , Chan Dick C. , Mata Pedro , Watts Gerald F.
Published: April 2022

Elevated lipoprotein(a) [Lp(a)], a predominantly genetic disorder, is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valvular disease, particularly in patients with familial hypercholesterolemia (FH), a Tier I genomic condition. The combination from birth of the cumulative exposure to elevated plasma concentrations of both Lp(a) and low-density lipoprotein is particularly detrimental and explains the enhanced morbidity and mortality risk observed in patients with both conditions. An excellent opportunity to identify at-risk patients with hyper-Lp(a) at increased risk of ASCVD is to test for hyper-Lp(a) during cascade testing for FH. With probands having FH and hyper-Lp(a), the yield of detection of hyper-Lp(a) is 1 individual for every 2.1–2.4 relatives tested, whereas the yield of detection of both conditions is 1 individual for every 3–3.4 relatives tested. In this article, we discuss the incorporation of assessment of Lp(a) in the cascade testing in FH as a feasible and crucial part of models of care for FH. We also propose a simple management tool to help physicians identify and manage elevated Lp(a) in FH, with implications for the care of Lp(a) beyond FH, noting that the clinical use of RNA therapeutics for specifically targeting the overproduction of Lp(a) in at risk patients is still under investigation.
Targeting PARP1 to Enhance Anticancer Checkpoint Immunotherapy Response: Rationale and Clinical Implications
Authors: Wanderley Carlos Wagner S. , Correa Tatiana Strava , Scaranti Mariana , Cunha Fernando Queiroz , Barroso-Sousa Romualdo
Published: April 2022

Reinvigorating the antitumor immune response using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of several malignancies. However, extended use of ICIs has resulted in a cancer-specific response. In tumors considered to be less immunogenic, the response rates were low or null. To overcome resistance and improve the beneficial effects of ICIs, novel strategies focused on ICI-combined therapies have been tested. In particular, poly ADP-ribose polymerase inhibitors (PARPi) are a class of agents with potential for ICI combined therapy. PARPi impairs single-strand break DNA repair; this mechanism involves synthetic lethality in tumor cells with deficient homologous recombination. More recently, novel evidence indicated that PAPRi has the potential to modulate the antitumor immune response by activating antigen-presenting cells, infiltrating effector lymphocytes, and upregulating programmed death ligand-1 in tumors. This review covers the current advances in the immune effects of PARPi, explores the potential rationale for combined therapy with ICIs, and discusses ongoing clinical trials.
Multiomics Studies Investigating Recurrent Pregnancy Loss: An Effective Tool for Mechanism Exploration
Authors: Li Jianan , Wang Linlin , Ding Jinli , Cheng Yanxiang , Diao Lianghui , Li Longfei , Zhang Yan , Yin Tailang
Published: April 2022

Patients with recurrent pregnancy loss (RPL) account for approximately 1%-5% of women aiming to achieve childbirth. Although studies have shown that RPL is associated with failure of endometrial decidualization, placental dysfunction, and immune microenvironment disorder at the maternal-fetal interface, the exact pathogenesis remains unknown. With the development of high-throughput technology, more studies have focused on the genomics, transcriptomics, proteomics and metabolomics of RPL, and new gene mutations and new biomarkers of RPL have been discovered, providing an opportunity to explore the pathogenesis of RPL from different biological processes. Bioinformatics analyses of these differentially expressed genes, proteins and metabolites also reflect the biological pathways involved in RPL, laying a foundation for further research. In this review, we summarize the findings of omics studies investigating decidual tissue, villous tissue and blood from patients with RPL and identify some possible limitations of current studies.
Biological Markers in Early Multiple Sclerosis: the Paved Way for Radiologically Isolated Syndrome
Authors: Rival Manon , Galoppin Manon , Thouvenot Eric
Published: April 2022

Radiologically Isolated Syndrome (RIS) is characterized by MRI-typical brain lesions fulfilling the 2009 Okuda criteria, detected in patients without clinical conditions suggestive of MS. Half of all RIS patients convert to MS within 10 years. The individual course of the disease, however, is highly variable with 12% of RIS converting directly to progressive MS. Demographic and imaging markers have been associated with the risk of clinical MS in RIS: male sex, younger age, infra-tentorial, and spinal cord lesions on the index scan and gadolinium-enhancing lesions on index or follow-up scans. Although not considered as a distinct MS phenotype, RIS certainly shares common pathological features with early active and progressive MS. In this review, we specifically focus on biological markers that may help refine the risk stratification of clinical MS and disability for early treatment. Intrathecal B-cell activation with cerebrospinal fluid (CSF) oligoclonal bands, elevated kappa free light chains, and cytokine production is specific to MS, whereas neurofilament light chain (NfL) levels reflect disease activity associated with neuroaxonal injury. Specific microRNA profiles have been identified in RIS converters in both CSF and blood. CSF levels of chitinases and glial acidic fibrillary protein (GFAP) reflecting astrogliosis might help predict the evolution of RIS to progressive MS. Innovative genomic, proteomic, and metabolomic approaches have provided several new candidate biomarkers to be explored in RIS. Leveraging data from randomized controlled trials and large prospective RIS cohorts with extended follow-up to identify, as early as possible, biomarkers for predicting greater disease severity would be invaluable for counseling patients, managing treatment, and monitoring.
Pathogen Prevalence Modulates Medication Behavior in Ant Formica fusca
Authors: Rissanen Jason , Helanterä Heikki , Freitak Dalial
Published: April 2022

Ants face unique challenges regarding pathogens, as the sociality which has allowed them to form large and complex colonies also raises the potential for transmission of disease within them. To cope with the threat of pathogens, ants have developed a variety of behavioral and physiological strategies. One of these strategies is self-medication, in which animals use biologically active compounds to combat pathogens in a way which would be harmful in the absence of infection. Formica fusca are the only ants that have previously been shown to successfully self-medicate against an active infection caused by a fungal pathogen by supplementing their diet with food containing hydrogen peroxide. Here, we build on that research by investigating how the prevalence of disease in colonies of F. fusca affects the strength of the self-medication response. We exposed either half of the workers of each colony or all of them to a fungal pathogen and offered them different combinations of diets. We see that workers of F. fusca engage in self-medication behavior even if exposed to a low lethal dose of a pathogen, and that the strength of that response is affected by the prevalence of the disease in the colonies. We also saw that the infection status of the individual foragers did not significantly affect their decision to forage on either control food or medicinal food as uninfected workers were also foraging on hydrogen peroxide food, which opens up the possibility of kin medication in partially infected colonies. Our results further affirm the ability of ants to self-medicate against fungal pathogens, shed new light on plasticity of self-medication and raise new questions to be investigated on the role self-medication has in social immunity.