bluuebunny/crossref_metadata_2025 huggingface dataset:
Desain Aplikasi Android-Based Integrated Management of Chilhood Illness (IMCI)
Authors: Nurmawati Ida
Published: August 2021

Integrated management of Chilhood Illness (IMCI) is an integrated approach in the management of children illness aged 0-59 months or less than 5 years as a whole. The development of technology and information allows the development of IMCI into information system can easy use for user. This study was an operational research that aimed to design android-based IMCI applications. Application design was done by creating flowchart, data flow diagram (DFD), entity relationship diagram (ERD), and IMCI application interface. IMCI application design results allowed the user to perform automatic disease assessment and classification as well as giving first action for childhood illness automatically. Design IMCI application was also integrated with web applications in first-level health services to produce reports. The design of android-based IMCI applications was expected to help the discovery of sick chilhood quickly. Therefore it is necessary to empower health cadres who have been trained to help find sick chilhood in the neighborhood.

Keywords: android; childhood illness; IMCI

ABSTRAK

Manajemen terpadu balita sakit atau Integrated Management of Childhood Illnes (IMCI) merupakan suatu pendekatan terpadu atau terintegrasi dalam penatalaksanaan balita sakit dengan fokus kepada kesehatan anak usia 0-59 bulan atau kurang dari 5 tahun secara menyeluruh. Perkembangan teknologi dan informasi memungkinkan pengembangan MTBS ke dalam sistem informasi yang mudah digunakan pengguna. Penelitian ini merupakan operational research yang bertujuan untuk merancang aplikasi IMCI berbasis android. Perancangan aplikasi dilakukan dengan membuat flowchart, data flow diagram (DFD), entity relationship diagram (ERD), dan interface aplikasi IMCI. Hasil perancangan aplikasi IMCI memungkinkan user untuk melakukan penilaian dan klasifikasi penyakit secara otomatis serta pemberian tindakan pertama bagi balita sakit secara otomatis. Perancangan aplikasi IMCI juga diintegrasikan dengan aplikasi web dimana admin pelayanan kesehatan tingkat pertama sebagai usernya untuk menghasilkan laporan berupa data balita, resep, dan penyakit. Perancangan aplikasi IMCI berbasis android ini diharapkan mampu membantu penemuan balita sakit secara cepat. Oleh karena itu perlu memberdayakan kader kesehatan yang telah dilatih untuk membantu menemukan balita sakit di lingkungan sekitar.

Kata kunci: android; balita sakit; IMCI
Wobble Editing of Cre-box by Unspecific CRISPR/Cas9 Causes CCR Release and Phenotypic Changes in Bacillus pumilus
Authors: Wang Yingxiang , Cao Linfeng , Bi Meiying , Wang Sicheng , Chen Meiting , Chen Xingyu , Ying Ming , Huang Lei
Published: August 2021

CRISPR-associated Cas9 endonuclease (CRISPR/Cas9) systems are widely used to introduce precise mutations, such as knocking in/out at targeted genomic sites. Herein, we successfully disrupted the transcription of multiple genes in Bacillus pumilus LG3145 using a series of unspecific guide RNAs (gRNAs) and UgRNA:Cas9 system-assisted cre-box editing. The bases used as gRNAs shared 30–70% similarity with a consensus sequence, a cis-acting element (cre-box) mediating carbon catabolite repression (CCR) of many genes in Bacillus. This triggers trans-crRNA:Cas9 complex wobble cleavage up/downstream of cre sites in the promoters of multiple genes (up to 7), as confirmed by Sanger sequencing and next-generation sequencing (NGS). LG3145 displayed an obvious CCR release phenotype, including numerous secondary metabolites released into the culture broth, ∼ 1.67 g/L white flocculent protein, pigment overflow causing orange-coloured broth (absorbance = 309 nm), polysaccharide capsules appearing outside cells, improved sugar tolerance, and a two-fold increase in cell density. We assessed the relationship between carbon catabolite pathways and phenotype changes caused by unspecific UgRNA-directed cre site wobble editing. We propose a novel strategy for editing consensus targets at operator sequences that mediates transcriptional regulation in bacteria.
Atrial Cardiomyopathy: An Emerging Cause of the Embolic Stroke of Undetermined Source
Authors: Ning Yuye , Tse Gary , Luo Guogang , Li Guoliang
Published: August 2021

Nearly 30% of ischemic strokes have an unknown cause, which are referred to as cryptogenic strokes (CS). Imaging studies suggest that a large proportion of these patients show features that are consistent with embolism, and thus the term embolic stroke of undetermined source (ESUS) was proposed to describe these CS patients. Atrial cardiomyopathy predisposes to thrombus formation and thus embolic stroke even in the absence of atrial fibrillation (AF). This may provide a mechanistic link with ESUS, suggesting that anticoagulant therapy may be more beneficial than antiplatelet therapy in ESUS patients with atrial cardiomyopathy. The present review discusses the concept of atrial cardiomyopathy and ESUS and the relationship between them based on the mechanisms and clinical evidence, suggests that atrial cardiomyopathy may be a potential mechanism of ESUS, and highlights a theoretical basis that supports that anticoagulant therapy may be more applicable to ESUS patients with atrial cardiomyopathy and aims to help us better understand and identify the risk of ESUS, thereby improving the management of these patients in clinical practice.
Congenital Heart Disease: An Immunological Perspective
Authors: Singampalli Kavya L. , Jui Elysa , Shani Kevin , Ning Yao , Connell Jennifer P. , Birla Ravi K. , Bollyky Paul L. , Caldarone Christopher A. , Keswani Sundeep G. , Grande-Allen Kathryn Jane
Published: August 2021

Congenital heart disease (CHD) poses a significant global health and economic burden—despite advances in treating CHD reducing the mortality risk, globally CHD accounts for approximately 300,000 deaths yearly. Children with CHD experience both acute and chronic cardiac complications, and though treatment options have improved, some remain extremely invasive. A challenge in addressing these morbidity and mortality risks is that little is known regarding the cause of many CHDs and current evidence suggests a multifactorial etiology. Some studies implicate an immune contribution to CHD development; however, the role of the immune system is not well-understood. Defining the role of the immune and inflammatory responses in CHD therefore holds promise in elucidating mechanisms underlying these disorders and improving upon current diagnostic and treatment options. In this review, we address the current knowledge coinciding CHDs with immune and inflammatory associations, emphasizing conditions where this understanding would provide clinical benefit, and challenges in studying these mechanisms.
Designing Oral Health Curriculum That Facilitates Greater Integration of Oral Health Into Overall Health
Authors: Mays Keith A.
Published: August 2021

For several decades, health professions education has been transforming; pedagogical constructs such as active learning, recorded lectures, electronic assessment, asynchronous content delivery, and interprofessional education and practice. However, the typical oral health curriculum has need for further transformation to ensure graduates' ability to function in an integrated health system. There is significant literature outlining associations between oral health and overall health, therefore, it is paramount that oral health learners develop skills to collaborate in an integrated model. Satcher, in 2000, outlined the gravity of oral health inequities and the importance of oral health. He said, “Too little time is devoted to oral health and disease topics in the education of non-dental health professional.” However, on the contrary typical oral health curriculum provide knowledge acquisition of topics related to overall health but isn't specifically designed to guide integrated care. In order to increase integrated care, groups like the Interprofessional Education Collaborative (IPEC) have developed competencies for interprofessional education and collaborative practice that guides the training of health professionals. One way to improve integration is accreditation standards that guide transformation as well incorporate IPEC competencies. Having competencies is important to prepare learners to function in clinics like Kaiser Permanente's medical-dental integration model that rely upon teams and teamwork and clarity of roles and responsibilities. This manuscript outlines principle of oral health curriculum that facilitate graduates ability to work in an integrated health system and how that contributes to the improvement overall health of patients.
Emerging Trends and Research Foci in Cataract Genes: A Bibliometric and Visualized Study
Authors: Zhu Hongli , Zhang Zhichang
Published: August 2021

Background: Approximately 50% of cataracts are associated with genetic factors. Genetic etiology and molecular mechanisms based on gene research increase the understanding of cataracts and provide direction for diagnosis and intervention. In the present study, SCIE papers related to the modeling of cataract gene research from 2010–2019 were evaluated and qualitative and quantitative analyses with modeling performed.

Methods: The SCIE database was searched on July 6, 2021 for cataract gene publications and relevant papers published since 2010 were considered for review. Subsequently, 1,904 SCIE papers associated with cataract genes from 2010–2019 were analyzed using a bibliometric method. The publication, country, institution, journal, references, knowledgebase, keywords, and research hotspots of the papers were analyzed using an online analysis platform of literature metrology, bibliographic item co-occurrence matrix builder (BICOMB), CiteSpace V, and VOS viewer analysis tool.

Results: 78 countries published the related articles, and the United States ranks of America had the most publications. Two thousand seven hundred and eighty three institutions contributed to the related publications. Fudan University had the most publications. The reference clusters of SCI papers were clustered into six categories, namely, causing congenital cataract-microcornea syndrome, functional snp, cataractous lenses, a1 mutation, foxe3 mutation, cell adhesion gene pvrl3, nid1 gene. The key words representing the research frontiers were cerebrotendinous xanthomatosis (2017-2019), oxidative stress (2017–2019).

Conclusion: This study provided a systematic, objective and comprehensive analysis of the literature related to gene research of cataract. Moreover, this study demonstrated the current hotspots and the future trends in the field of gene research of cataract. This review will help ophthalmologist to discern the dynamic evolution of cataract gene research, as well as highlight areas for future research.
Validation of Genes Affecting Rice Grain Zinc Content Through Candidate Gene-Based Association Analysis
Authors: Liu Jindong , Zhan Junhui , Chen Jingguang , Lu Xiang , Zhi Shuai , Ye Guoyou
Published: August 2021

Several key genes governing Zn homeostasis and grain zinc content (GZC) have been functionally characterized. However, the effects of these genes in diverse breeding populations have not been evaluated; thus, their availability in breeding is unclear. In this study, the effects of 65 genes related to rice zinc responses on GZC were evaluated using two panels of breeding lines, and the superior haplotypes were identified. One panel consisted of mega varieties from the International Rice Research Institute (IRRI), South Asia, and Southeast Asia (SEA), and the other panel is breeding lines/varieties from South China (SC). In addition, a multiparent advanced generation intercross (MAGIC) population, named as DC1, was also employed. Three analytical methods, single-locus mixed linear model (SL-MLM), multilocus random-SNP-effect mixed linear model (mrMLM), and haplotype-based association analysis (Hap-AA), were applied. OsIDEF1 (which explained 12.3% of the phenotypic variance) and OsZIFL7 (8.3–9.1%), OsZIP7 (18.9%), and OsIRT1 (17.9%) were identified by SL-MLM in SEA and SC, respectively, whereas no gene was significantly associated with GZC in DC1. In total, five (OsNRAMP6, OsYSL15, OsIRT1, OsIDEF1, and OsZIFL7, 7.70–15.39%), three (OsFRDL1, OsIRT1, and OsZIP7, 11.87–17.99%), and two (OsYSL7 and OsZIP7, 9.85–10.57%) genes were detected to be significantly associated with GZC in SEA, SC, and DC1 by mrMLM, respectively. Hap-AA indicated that Hap1-OsNRAMP5, Hap5-OsZIP4, Hap1-OsIRT1, Hap3-OsNRAMP6, Hap6-OsMTP1, and Hap6-OsYSL15 had the largest effects for GZC in SEA, whereas Hap3-OsOPT7, Hap4-OsIRT2, Hap4-OsZIP7, Hap5-OsIRT1, and Hap5-OsSAMS1 were the most significant in the SC population. Besides, superior alleles were also identified for the significant genes. The genes significantly associated with GZC and their superior haplotypes identified in different panels could be used in enhancing GZC through molecular breeding, which could further address the problem of Zn malnutrition among rice consumers.
Dynamic Network Biomarker of Pre-Exhausted CD8+ T Cells Contributed to T Cell Exhaustion in Colorectal Cancer
Authors: Hu Jiaqi , Han Chongyin , Zhong Jiayuan , Liu Huisheng , Liu Rui , Luo Wei , Chen Pei , Ling Fei
Published: August 2021

Immunotherapy has achieved positive clinical responses in various cancers. However, in advanced colorectal cancer (CRC), immunotherapy is challenging because of the deterioration of T-cell exhaustion, the mechanism of which is still unclear. In this study, we depicted CD8+ T-cell developmental trajectories and characterized the pre-exhausted T cells isolated from CRC patients in the scRNA-seq data set using a dynamic network biomarker (DNB). Moreover, CCT6A identified by DNB was a biomarker for pre-exhausted T-cell subpopulation in CRC. Besides, TUBA1B expression was triggered by CCT6A as DNB core genes contributing to CD8+ T cell exhaustion, indicating that core genes serve as biomarkers in pre-exhausted T cells. Remarkably, both TUBA1B and CCT6A expressions were significantly associated with the overall survival of COAD patients in the TCGA database (p = 0.0082 and p = 0.026, respectively). We also observed that cellular communication between terminally differentiated exhausted T cells and pre-exhausted T cells contributes to exhaustion. These findings provide new insights into the mechanism of T-cell exhaustion and provide clue for targeted immunotherapy in CRC.
Distinct Bioenergetic Features of Human Invariant Natural Killer T Cells Enable Retained Functions in Nutrient-Deprived States
Authors: Khurana Priya , Burudpakdee Chakkapong , Grupp Stephan A. , Beier Ulf H. , Barrett David M. , Bassiri Hamid
Published: August 2021

Invariant natural killer T (iNKT) cells comprise a unique subset of lymphocytes that are primed for activation and possess innate NK-like functional features. Currently, iNKT cell-based immunotherapies remain in early clinical stages, and little is known about the ability of these cells to survive and retain effector functions within the solid tumor microenvironment (TME) long-term. In conventional T cells (TCONV), cellular metabolism is linked to effector functions and their ability to adapt to the nutrient-poor TME. In contrast, the bioenergetic requirements of iNKT cells – particularly those of human iNKT cells – at baseline and upon stimulation are not well understood; neither is how these requirements affect effector functions such as production of cytokines and cytolytic proteins. We find that unlike TCONV, human iNKT cells are not dependent upon glucose or glutamine for these effector functions upon stimulation with anti-CD3 and anti-CD28. Additionally, transcriptional profiling revealed that stimulated human iNKT cells are less glycolytic than TCONVand display higher expression of fatty acid oxidation (FAO) and adenosine monophosphate-activated protein kinase (AMPK) pathway genes. Furthermore, stimulated iNKT cells displayed higher mitochondrial mass and membrane potential relative to TCONV. Real-time Seahorse metabolic flux analysis revealed that stimulated human iNKT cells utilize fatty acids as substrates for oxidation more than stimulated TCONV.Together, our data suggest that human iNKT cells possess different bioenergetic requirements from TCONVand display a more oxidative metabolic program relative to effector TCONV. Importantly, iNKT cell-based immunotherapeutic strategies could co-opt such unique features of iNKT cells to improve their efficacy and longevity of anti-tumor responses.
Impact of Seawater Temperature on Coral Reefs in the Context of Climate Change. A Case Study of Cu Lao Cham – Hoi An Biosphere Reserve
Authors: Dao Hung N. , Vu Hang T. , Kay Susan , Sailley Sevrine
Published: August 2021

Coral reefs are a natural habitat for many species, as well as being of high economic and touristic significance. However, they represent an extremely sensitive ecosystem with a narrow ecological limit: prolonged high temperatures can lead to bleaching, in which corals expel their symbiotic algae and eventually corals will degrade and die. Based on climate change projections from the Blue Communities regional model, using linear regression, exponential regression, polynomial regression, we found that by the decades 2041–2050 and 2051–2060, whether with RCP 4.5 or RCP 8.5, the environmental temperature will change beyond the coral capacity threshold. Of particular concern is RCP 8.5, where the number of weeks per decade in which SST exceeds the threshold of coral reef bleaching is up to 55, compared to 0 at the beginning of the century. As well, the El Niño phenomenon often heats up waters to abnormally high temperatures in Cu Lao Cham and, it is projected to rise even further. Consequently, the combination of climate change and El Niño will cause abnormal increases in the seawater environment beyond the coral resistance threshold, leading to degradation of this internationally important site. Decisive and practical action must be taken to deal with climate change in this part of the world.
Medical Affairs in Pharmaceutical Companies and Related Pharmaceutical Regulations in Japan
Authors: Maeda Hideki
Published: August 2021

Medical affairs has received a lot of attention in recent years in Japan, but it is also often misunderstood or poorly understood in the healthcare industry in Japan. In the United States, the function of medical affairs has been established for a long time, whereas its history in Japan is relatively short. Many scandals in clinical trials occurred with inappropriate relationship between medical doctors and the sales departments of pharmaceutical companies from 2012. These incidents undermined confidence in clinical trials in Japan and triggered the enforced separation of sales departments from the conduct of post-marketing clinical trials and evidence generation. There have been growing compliance issues identified in marketing and sales practices, and off-label promotion is also becoming an issue in Japan. These issues resulted in the establishment of independent medical affairs departments from sales departments in pharmaceutical companies operating in Japan. Due to the short history of medical affairs in Japan, the roles and responsibilities vary between companies in Japan. Medical affairs departments aim to fulfill unmet medical needs through the generation of scientific evidence and to deliver scientific value to key stakeholders and patients. People working in medical affairs need to engage in scientific exchange activities with key opinion leaders independent of sales departments. Through these activities, medical affairs ensures that patients receive optimal medical care. Medical affairs in Japan is still developing, and its roles, responsibilities, and functions are improving. This article covers the history of medical affairs in Japan and the current status and future perspectives of medical affairs in Japan.
Role of Th22 Cells in Human Viral Diseases
Authors: Gong Jianguang , Zhan Huifang , Liang Yan , He Qiang , Cui Dawei
Published: August 2021

Naive CD4+ T cells can differentiate into different cell subsets after receiving antigen stimulation, which secrete corresponding characteristic cytokines and thereby exert biological effects in various diseases. Th22 cells, a novel subset of CD4+ T cells, are different from Th1, Th2, Th17, and Treg cell subsets, which have been discovered in recent years. They can express CCR4, CCR6, and CCR10 molecules and secrete IL-22, IL-13, and TNF-α. They are not able to secrete IL-17, IL-4, and interferon-γ (IFN-γ). IL-22 is considered as a major effector molecule of Th22 cells whose functions and mechanisms of regulating cell differentiation have been constantly improved. In this review, we provide an overview of the origin, differentiation of Th22 cells. Moreover, we also describe the interrelationships between Th22 cells and Th17, Th1, and Th2 cells. Additionally, the role of Th22 cells were discussed in human diseases with virus infection, which will provide novel insight for the prevention and treatment of viral infection in human.
Dermatoscopic Features of Naevi During Pregnancy—A Mini Review
Authors: Cosgarea Ioana , Trevisan-Herraz Marco , Ungureanu Loredana , Zalaudek Iris
Published: August 2021

Changes in melanocytic naevi and development of new naevi have been reported in pregnant women. The association between pregnancy and melanoma is a controversial topic. We conducted this review to identify the dermatoscopic changes that occur in naevi during pregnancy that could facilitate in distinguishing benign from suspicious lesions. Medline, Scopus, and Embase datasets were reviewed for clinical studies on dermatoscopic characteristics of melanoma and naevus in pregnancy. Six cohort studies with a total of 258 patients with 1,167 skin lesions that were examined fulfilled the conditions to be included in the review. None of the patients developed melanoma. Development of new naevi, when reported, was observed in less than half of the participants. The most frequent observed dermatoscopic change among the studies was the increase in the number of dots. Development of new vessels, hypo- and hyperpigmentations and changes in the pigment network were common described changes. The included studies were heterogeneous not allowing head-to-head comparisons between them. Robust and larger studies of dermatoscopic evaluation of naevi in pregnant women are needed to determine high-risk dermatoscopic characteristics.
Resource Allocation During the Transition to Diazotrophy in Klebsiella oxytoca
Authors: Waite Christopher J. , Lindström Battle Anya , Bennett Mark H. , Carey Matthew R. , Hong Chun K. , Kotta-Loizou Ioly , Buck Martin , Schumacher Jörg
Published: August 2021

Free-living nitrogen-fixing bacteria can improve growth yields of some non-leguminous plants and, if enhanced through bioengineering approaches, have the potential to address major nutrient imbalances in global crop production by supplementing inorganic nitrogen fertilisers. However, nitrogen fixation is a highly resource-costly adaptation and is de-repressed only in environments in which sources of reduced nitrogen are scarce. Here we investigate nitrogen fixation (nif) gene expression and nitrogen starvation response signaling in the model diazotroph Klebsiella oxytoca (Ko) M5a1 during ammonium depletion and the transition to growth on atmospheric N2. Exploratory RNA-sequencing revealed that over 50% of genes were differentially expressed under diazotrophic conditions, among which the nif genes are among the most highly expressed and highly upregulated. Isotopically labelled QconCAT standards were designed for multiplexed, absolute quantification of Nif and nitrogen-stress proteins via multiple reaction monitoring mass spectrometry (MRM-MS). Time-resolved Nif protein concentrations were indicative of bifurcation in the accumulation rates of nitrogenase subunits (NifHDK) and accessory proteins. We estimate that the nitrogenase may account for more than 40% of cell protein during diazotrophic growth and occupy approximately half the active ribosome complement. The concentrations of free amino acids in nitrogen-starved cells were insufficient to support the observed rates of Nif protein expression. Total Nif protein accumulation was reduced 10-fold when the NifK protein was truncated and nitrogenase catalysis lost (nifK1–1203), implying that reinvestment of de novo fixed nitrogen is essential for further nif expression and a complete diazotrophy transition. Several amino acids accumulated in non-fixing ΔnifLA and nifK1–1203 mutants, while the rest remained highly stable despite prolonged N starvation. Monitoring post-translational uridylylation of the PII-type signaling proteins GlnB and GlnK revealed distinct nitrogen regulatory roles in Ko M5a1. GlnK uridylylation was persistent throughout the diazotrophy transition while a ΔglnK mutant exhibited significantly reduced Nif expression and nitrogen fixation activity. Altogether, these findings highlight quantitatively the scale of resource allocation required to enable the nitrogen fixation adaptation to take place once underlying signaling processes are fulfilled. Our work also provides an omics-level framework with which to model nitrogen fixation in free-living diazotrophs and inform rational engineering strategies.
White Matter Microstructural Damage Associated With Gait Abnormalities in Idiopathic Normal Pressure Hydrocephalus
Authors: Tang Yan-min , Yao Ye , Xu Shuai , Li Xin , Hu Fan , Wang He , Ding Jing , Wang Xin
Published: August 2021

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a common disease in elderly adults. Patients with iNPH are generally characterized by progressive gait impairment, cognitive deficits, and urinary urgency and/or incontinence. A number of radiographic studies have shown that iNPH patients have enlarged ventricles and altered brain morphology; however, few studies have focused on the relationships between altered brain structure and gait dysfunction due to iNPH. Thus, this study aimed to evaluate the abnormalities of white matter (WM) correlated with gait impairment in iNPH patients and to gain a better understanding of its underlying pathology.

Methods: Fifteen iNPH patients (five women, 10 men) were enrolled in this study, and each patient’s demographic and gait indices were collected. First, we performed a correlation analysis between the demographic and gait indices. Then, all gait indices were grouped according to the number of WM hyperintensities (WMH) among each WM tract (JHU WM tractography atlas), to perform comparative analysis.

Results: Considering sex and illness duration as covariates, correlation analysis showed a significantly negative correlation between step length (r = −0.80, p = 0.001), pace (r = −0.84, p = 2.96e-4), and age. After removing the effects of age, sex, and illness duration, correlation analysis showed negative correlation between step length (r = −0.73, p = 0.007), pace (r = −0.74, p = 0.005), and clinical-grade score and positive correlation between 3-m round trip time (r = 0.66, p = 0.021), rising time (r = 0.76, p = 0.004), and clinical-grade score. Based on WMH of each white matter tract, gait indices showed significant differences (p < 0.05/48, corrected by Bonferroni) between fewer WMH patients and more WMH in the middle cerebellar peduncle, left medial lemniscus, left posterior limb of the internal capsule (IC), and right posterior limb of the IC.

Conclusions: Our results indicated that iNPH patients exhibited gait-related WM abnormalities located in motor and sensory pathways around the ventricle, which is beneficial to understand the underlying pathology of iNPH.
Differences Between Exergaming Rehabilitation and Conventional Physiotherapy on Quality of Life in Parkinson's Disease: A Systematic Review and Meta-Analysis
Authors: Elena Papamichael , Demetris Solou , Christina Michailidou , Marios Papamichail
Published: August 2021

Parkinson's disease (PD) is a neurodegenerative condition with both motor and non-motor symptoms affecting the quality of life (QoL) of older adults. Exergaming rehabilitation allows the interaction of the subject with digital games through the implementation of repetitive functional activities. Conventional physiotherapy uses patient-centered programs that include a variety of active exercises. The aim of this review was to look into the effectiveness of exergaming rehabilitation on the QoL of people with PD and compare it with conventional physiotherapy. Five electronic databases were searched for eligible studies until February 2021. For the statistical analysis, the mean, standard deviation, and 95% confidence interval were used to calculate effect sizes between groups. To determine heterogeneity, statistical indexI2was used. A total of 548 participants were included in 14 studies. Exergaming rehabilitation related with improved QoL (p= 0.687, 95% CI: −1.682 to −0.734), balance (p= 0.039, 95% CI: 0.364–13.689), (p= 0.018, 95% CI: 0.446–4.830), and gait (p= 0.005, 95% CI: 0.351–1.924). No significant difference was found between groups regarding the Unified Parkinson's Disease Rating Scale (p= 0.196, 95% CI: −5.970 to 1.225) and for the Timed Up and Go Test (p= 0.12, 95% CI: 0.446–4.830). Exergames as a rehabilitation method can be used to provide alternative interactive intervention with positive results for QoL in people with PD. Further investigation is needed to assess the effect on mental health in this population group.
The Relationship Between Peritumoral Brain Edema and the Expression of Vascular Endothelial Growth Factor in Vestibular Schwannoma
Authors: You Hong-Hai , Chen Xiao-Yong , Chen Jin-Yuan , Bai Yue , Chen Fu-Xiang
Published: August 2021

Objective: This study aimed to explore the potential mechanism of peritumoral brain edema (PTBE) formation in vestibular schwannoma (VS) by detecting intra-tumoral vascular endothelial growth factor (VEGF) expression.

Methods: Between January 2018 and May 2021, 15 patients with PTBE and 25 patients without PTBE were included in the analysis. All patients enrolled in our study underwent surgery in our institution. Expression level of VEGF and microvessel density (MVD) between the two groups were analyzed. Edema index (EI) of each patient with PTBE was calculated.

Results: In the PTBE group, the average of EI was 1.53 ± 0.22. VEGF expression levels were significantly enhanced in the PTBE group compared with the non-PTBE group (p < 0.001). The expression level of VEGF in the PTBE group and non-PTBE group was 1.14 ± 0.21 and 0.52 ± 0.09, respectively. Similarly, there were significantly different amounts of MVD in the two groups (p < 0.001). The amount of MVD in the PTBE group and non-PTBE group was 11.33 ± 1.59 and 6.28 ± 1.77, respectively. Correlation analysis showed a highly significant positive correlation between VEGF and MVD (r = 0.883, p < 0.001) and VEGF and EI (r = 0.876, p < 0.001).

Conclusion: Our study confirmed the close relationship among VEGF expression, tumor angiogenesis, and formation of PTBE in VS patients. It may be possible to develop new effective therapies to attenuate PTBE in VS for alleviation of symptoms and reduction of postoperative complication.
Neural Processing of Spectral and Durational Changes in Speech and Non-speech Stimuli: An MMN Study With Czech Adults
Authors: Nudga Natalia , Urbanec Josef , Oceláková Zuzana , Kremláček Jan , Chládková Kateřina
Published: August 2021

Neural discrimination of auditory contrasts is usually studied via the mismatch negativity (MMN) component of the event-related potentials (ERPs). In the processing of speech contrasts, the magnitude of MMN is determined by both the acoustic as well as the phonological distance between stimuli. Also, the MMN can be modulated by the order in which the stimuli are presented, thus indexing perceptual asymmetries in speech sound processing. Here we assessed the MMN elicited by two types of phonological contrasts, namely vowel quality and vowel length, assuming that both will elicit a comparably strong MMN as both are phonemic in the listeners’ native language (Czech) and perceptually salient. Furthermore, we tested whether these phonemic contrasts are processed asymmetrically, and whether the asymmetries are acoustically or linguistically conditioned. The MMN elicited by the spectral change between /a/ and /ε/ was comparable to the MMN elicited by the durational change between /ε/ and /ε:/, suggesting that both types of contrasts are perceptually important for Czech listeners. The spectral change in vowels yielded an asymmetrical pattern manifested by a larger MMN response to the change from /ε/ to /a/ than from /a/ to /ε/. The lack of such an asymmetry in the MMN to the same spectral change in comparable non-speech stimuli spoke against an acoustically-based explanation, indicating that it may instead have been the phonological properties of the vowels that triggered the asymmetry. The potential phonological origins of the asymmetry are discussed within the featurally underspecified lexicon (FUL) framework, and conclusions are drawn about the perceptual relevance of the place and height features for the Czech /ε/-/a/ contrast.
Adapting Medication for Type 2 Diabetes to a Low Carbohydrate Diet
Authors: Cucuzzella Mark , Riley Karen , Isaacs Diana
Published: August 2021

Healthcare professionals in the primary care setting need to be competent to safely adapt diabetes medications when patients with Type 2 Diabetes (T2D) alter their diet. Safe prescribing practice is supported through an understanding of the clinical evidence, basic science, and pharmacology of medications. This review article supports clinicians in the practical application of this knowledge to achieve safe practice. Traditional medical training and clinical practice for chronic disease has long revolved around the teaching of intensifying therapy and evidenced based prescribing, a crucial skill when chronic disease progresses. Now that we are witnessing remission of Type 2 Diabetes through nutritional interventions specifically low carbohydrate diets (LCD) we must apply the same effort and thought to de-prescribing as the underlying metabolic condition improves. There is minimal guidance in the literature on how to actively de-prescribe. The American Diabetes Association in theirStandards of Medical Care in Diabetes–2021acknowledges low carbohydrate nutritional therapy (LCD) as a viable option in the management of Type 2 Diabetes (T2D). Thus, the goal of our paper is to help close the gap between the clinical evidence, basic science, and pharmacology of T2D medications to the practical application and teamwork needed to facilitate safe medication reduction in the primary care setting when applied to a LCD. The LCD is an increasingly popular and effective option for managing T2D and can lead to an improvement in the condition, reduced medication burden, and contribute to significant weight loss. Safe initiation of a LCD in patients on medications requires significant monitoring and medication adjustments to decrease and eliminate the risk of hypoglycemia and hypotension. The health care team including clinicians in primary care, nursing, pharmacy and nutrition need to be competent in adjusting diabetes and antihypertensive medications to achieve safe and effective care. The most immediate and important adjustments are to insulin, sulfonylureas, SGLT2 inhibitors, blood pressure medications and diuretics. Interdisciplinary care teams can individualize therapy while following the guidance, which includes monitoring blood glucose and blood pressure closely, decreasing medications that can cause hypoglycaemia and hypotension, evaluating blood glucose and blood pressure data responses regularly, and open access communication with the team. The article is an international consensus document on de-prescribing that was put together by a multidisciplinary team of clinicians.
Dietary Inulin Regulated Gut Microbiota and Improved Neonatal Health in a Pregnant Sow Model
Authors: Li Hao , Ma Longteng , Zhang Longlin , Liu Nian , Li Zhiqing , Zhang Fan , Liu Xiang , Ma Xiaokang
Published: August 2021

This study aimed to investigate the relationship between maternal dietary fiber intake and piglet health. Multiparous sows were randomly assigned to two groups and fed diets without inulin (control group, n = 20) or 1.6% inulin (1.6IN group, n = 20). The results indicate that 1.6IN prevented the prolonged farrowing duration of sows (P < 0.05) and shortened the average piglet birth interval (P < 0.1). In addition, 1.6IN decreased the percentage of the piglet born weak and the percentage of the piglet with hyperthermia after birth (P < 0.01). Compared with the control group, the 1.6IN group had a lower concentration of urea nitrogen in the colostrum, and also prevented diarrhea, increased litter gain, survival rate, and average daily gain for suckling piglets (P < 0.05). Furthermore, 1.6IN decreased the relative abundance of Firmicutes, Cyanobacteria, and Streptococcus; increased the relative abundance of Bacteroidetes, Desulfovibrio, Paludibacter, CF231, and Prevotella. Overall, this study showed that maternal fiber nutrition during pregnancy regulated the health of offspring, and the response of the maternal intestinal microbes played an important role in intervening in the phenotype of sows and neonatal piglets.
Advances of Tumorigenesis, Diagnosis at Early Stage, and Cellular Immunotherapy in Gastrointestinal Malignancies
Authors: Zhu Haipeng , Liu Xiaojun
Published: August 2021

Globally, in 2018, 4.8 million new patients have a diagnosis of gastrointestinal (GI) cancers, while 3.4 million people died of such disorders. GI malignancies are tightly relevant to 26% of the world-wide cancer incidence and occupies 35% of all cancer-associated deaths. In this article, we principally investigated molecular and cellular mechanisms of tumorigenesis in five major GI cancers occurring at esophagus, stomach, liver, pancreas, and colorectal region that illustrate high morbidity in Eastern and Western countries. Moreover, through this investigation, we not only emphasize importance of the tumor microenvironment in development and treatment of malignant tumors but also identify significance of M2PK, miRNAs, ctDNAs, circRNAs, and CTCs in early detection of GI cancers, as well as systematically evaluate contribution of personalized precision medicine including cellular immunotherapy, new antigen and vaccine therapy, and oncolytic virotherapy in treatment of GI cancers.
Adaptive Attention Convolutional Neural Network for Liver Tumor Segmentation
Authors: Luan Shunyao , Xue Xudong , Ding Yi , Wei Wei , Zhu Benpeng
Published: August 2021

Purpose

Accurate segmentation of liver and liver tumors is critical for radiotherapy. Liver tumor segmentation, however, remains a difficult and relevant problem in the field of medical image processing because of the various factors like complex and variable location, size, and shape of liver tumors, low contrast between tumors and normal tissues, and blurred or difficult-to-define lesion boundaries. In this paper, we proposed a neural network (S-Net) that can incorporate attention mechanisms to end-to-end segmentation of liver tumors from CT images.

Methods

First, this study adopted a classical coding-decoding structure to realize end-to-end segmentation. Next, we introduced an attention mechanism between the contraction path and the expansion path so that the network could encode a longer range of semantic information in the local features and find the corresponding relationship between different channels. Then, we introduced long-hop connections between the layers of the contraction path and the expansion path, so that the semantic information extracted in both paths could be fused. Finally, the application of closed operation was used to dissipate the narrow interruptions and long, thin divide. This eliminated small cavities and produced a noise reduction effect.

Results

In this paper, we used the MICCAI 2017 liver tumor segmentation (LiTS) challenge dataset, 3DIRCADb dataset and doctors’ manual contours of Hubei Cancer Hospital dataset to test the network architecture. We calculated the Dice Global (DG) score, Dice per Case (DC) score, volumetric overlap error (VOE), average symmetric surface distance (ASSD), and root mean square error (RMSE) to evaluate the accuracy of the architecture for liver tumor segmentation. The segmentation DG for tumor was found to be 0.7555, DC was 0.613, VOE was 0.413, ASSD was 1.186 and RMSE was 1.804. For a small tumor, DG was 0.3246 and DC was 0.3082. For a large tumor, DG was 0.7819 and DC was 0.7632.

Conclusion

S-Net obtained more semantic information with the introduction of an attention mechanism and long jump connection. Experimental results showed that this method effectively improved the effect of tumor recognition in CT images and could be applied to assist doctors in clinical treatment.
Single-Cell Transcriptomics of Glioblastoma Reveals a Unique Tumor Microenvironment and Potential Immunotherapeutic Target Against Tumor-Associated Macrophage
Authors: Cui Xiaoteng , Wang Qixue , Zhou Junhu , Wang Yunfei , Xu Can , Tong Fei , Wang Hongjun , Kang Chunsheng
Published: August 2021

Background

The main immune cells in GBM are tumor-associated macrophages (TAMs). Thus far, the studies investigating the activation status of TAM in GBM are mainly limited to bulk RNA analyses of individual tumor biopsies. The activation states and transcriptional signatures of TAMs in GBM remain poorly characterized.

Methods

We comprehensively analyzed single-cell RNA-sequencing data, covering a total of 16,201 cells, to clarify the relative proportions of the immune cells infiltrating GBMs. The origin and TAM states in GBM were characterized using the expression profiles of differential marker genes. The vital transcription factors were examined by SCENIC analysis. By comparing the variable gene expression patterns in different clusters and cell types, we identified components and characteristics of TAMs unique to each GBM subtype. Meanwhile, we interrogated the correlation between SPI1 expression and macrophage infiltration in the TCGA-GBM dataset.

Results

The expression patterns of TMEM119 and MHC-II can be utilized to distinguish the origin and activation states of TAMs. In TCGA-Mixed tumors, almost all TAMs were bone marrow-derived macrophages. The TAMs in TCGA-proneural tumors were characterized by primed microglia. A different composition was observed in TCGA-classical tumors, which were infiltrated by repressed microglia. Our results further identified SPI1 as a crucial regulon and potential immunotherapeutic target important for TAM maturation and polarization in GBM.

Conclusions

We describe the immune landscape of human GBM at a single-cell level and define a novel categorization scheme for TAMs in GBM. The immunotherapy against SPI1 would reprogram the immune environment of GBM and enhance the treatment effect of conventional chemotherapy drugs.
Comparison of Pinoresinol and its Diglucoside on their ADME Properties and Vasorelaxant Effects on Phenylephrine-Induced Model
Authors: Pu Yiqiong , Cai Yiqing , Zhang Qi , Hou Tianling , Zhang Teng , Zhang Tong , Wang Bing
Published: August 2021

Pinoresinol (PINL) and pinoresinol diglucoside (PDG), two natural lignans found in Eucommia ulmoides Oliv. (Duzhong), have several pharmacological activities. However, there is no report available on their absorption, distribution, metabolism, and elimination (ADME) properties. Given the possible wide spectrum of their application in therapeutic areas, this area should be investigated. This work studied the in vitro ADME properties of PDG and PINL, including their kinetic solubility, permeability across monolayer cells (PAMPA), protein binding, and metabolic stabilities in liver microsomes. The in vivo pharmacokinetic study and in vitro vasorelaxant effects on isolated phenylephrine-induced aortic rings of PINL and PDG were also investigated. It was found that both of their kinetic solubility in PBS (pH 7.4) was greater than 100 μM, indicating that they are both soluble compounds. The permeability investigations (Peff) by PAMPA indicated that PINL had higher permeability than PDG (p < 0.05). Both components represented moderate plasma protein binding activities (average binding rate in human plasma: PINL 89.03%, PDG 45.21%) and low metabolic rate (t1/2 in human liver microsome: PINL 1509.5 min, PDG 1004.8 min). Furthermore, the results of pharmacokinetic studies indicated that PINL might be eliminated less quickly than PDG from the rat plasma, and its cumulative urinary excretion was much lower than that of PDG. The phenylephrine-induced aortic rings demonstrated concentration-dependent vasorelaxation in PDG, PINL, or their combination group. The vasorelaxant effects of PINL were more obvious than those of PDG, whereas the vasorelaxant effect of the combinations was significantly better than that of the single component (p < 0.05). The similarity or difference between PINL and its diglucoside in these pharmaceutical aspects may offer valuable insights into the further exploration of lignans and might contribute to relevant studies involving natural products with similar molecular structure and their glucosides.
Driving Waveform Design Based on Driving Process Fusion and Black Reference Gray Scale for Electrophoretic Displays
Authors: Wang Li , Ma Pengchang , Zhang Jitao , Wan Qiming
Published: August 2021

An electrophoretic display (EPD) is a kind of paper display technology, which has the advantages of ultra-low power consumption and readability under strong light. However, in an EPD-driving process, four stages are needed to finish the driving of a pixel erase original images, reset to black state, clear-to-white state, and write a new image. A white reference gray scale can be obtained before writing a new image, and this driving process may take too long for the comfort of reading. In this article, an EPD-driving waveform, which takes the black state as the reference gray, is proposed to reduce the driving time. In addition, the rules of direct current (DC) balance are also followed to prevent the charge from getting trapped in the driving backplane. The driving process is fused and there are two stages in the driving waveform: reset to black state and write the next image. First, the EPD is written to a stable black state according to the original gray scale driving waveform and the black state is used as the reference gray for the next image. Second, the new image is written by the second stage of the new driving waveform. The experimental results show that the proposed driving waveform has a better performance. Compared with the traditional driving waveform which has four stages, the driving time of the new driving waveform is reduced by nearly 50%.