bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic Profiling of Chinese Urothelial Carcinoma Patients
Authors: Yang Bo , Zhao Xiao , Wan Chong , Ma Xin , Niu Shaoxi , Guo Aitao , Wang Jieli , Wang Jinliang , Sun Decong , Jiao Shunchang
Published: August 2020

Background
Urothelial carcinoma (UC) is the most common genitourinary malignancy in China. In this study, we studied the genomic features in Chinese UC patients, and investigated the concordance of genetic alterations between serum circulating tumor free DNA (ctDNA) and matched tumor tissue.
Methods
A total of 112 UC patients were enrolled, and 31 of which were upper tract UC (UTUC) and 81 were UC of bladder (UCB), respectively. Utilizing target next-generation sequencing, we analyzed genomic alterations of 92 selected genes.
Results
94.64%, 86.61% and 62.50% of patients in our cohort were identified as having valid, oncogenic or actionable somatic alterations, respectively, and the most altered genes were TP53, KMT2D, KDM6A, FAT4, FAT1, CREBBP and ARID1A. HRAS (22.0% vs 3.7%) and KMT2D (59.26% vs 34.57%) were more altered in UTUC than in UCB in our cohort. Comparisons of somatic alterations of UCB and UTUC between our cohort and western cohorts revealed significant differences in gene prevalence. Notably, 28.57%, 17.86% and 47.32% of cases harbored alterations in FGFRs, ERBBs and DNA damage repair genes, respectively. Furthermore, 75% of patients carried non-benign germline variants, but only two (1.79%) were pathogenic. By comparison of ctDNA and matched tumor tissue, the overall concordance for genomic alterations was 42.97% (0-100%). 47.25% of alterations detected in ctDNA were not detected in the matched tissue, and 25.58% of which were oncogenic.
Conclusions
We found a unique genomic feature of Chinese UC patients. A good concordance of genomic features between ctDNA and tissue samples were identified.
Basil interspecific hybridization and transcriptome study indicates altered developmental and metabolic gene expression
Authors: Shah Saumya , Rastogi Shubhra , Vashisth Divya , . Mytrai , Lal R K , Lavania Umesh Chandra , Shasany Ajit
Published: August 2020

Background
In order to understand the developmental modulation of transcriptome and associated gene expression in inter-genomic combinations, a systematic study was planned using two diverse yet closely related species of Ocimum, targeting their hybrid F1 and derived amphidiploid (colchiploid of F1 hybrid). The existing developmental alterations between F1 and amphidiploid through phenotypical and anatomical assessments were analyzed.
Results
Study of several genes and transcription factors putatively involved in the growth and developmental processes of plants clearly amalgamates the transcriptome data linking the phenotypic differences in F1 and amphidiploid. Additionally, differentially expressed genes of stomatal patterning and development revealed their involvement leading to higher density of stomata in F1 while larger size of stomata in the amphidiploid. Absence of 8,330 transcripts of interspecific hybrid F1 in its amphidiploid and exclusive presence of two detected transcripts in amphidiploid provides a set of genes to analyze the suppressed or activated functions between F1 and amphidiploid. Estimation of chlorophyll, lignin, flavonoid and phenylpropenes (eugenol and methyleugenol) content were correlated with the average FPKM and digital gene expression values in F1 and amphidiploid.
Conclusion
This is the first investigation which describes the genes and transcription factors influenced by interspecific hybridization leading to developmental changes and alleviation of intergenomic instability in amphidiploid.
Chromosomal painting of the sandpiper (Actitis macularius) detects several fissions for the Scolopacidae family (Charadriiformes)
Authors: Pinheiro Melquizedec Luiz Silva , Nagamachi Cleusa Yoshiko , Ribas Talita Fernanda Augusto , Diniz Cristovam Guerreiro , O´Brien Patricia Caroline Mary , Ferguson-Smith Malcolm Andrew , Yang Fengtang , Pieczarka Julio Cesar
Published: August 2020

Background: The Scolopacidae family (Suborder Scolopaci, Charadriiformes) is composed of sandpipers and snipes; these birds are long-distance migrants that show great diversity in their behavior and habitat use. Cytogenetic studies in the Scolopacidae family show the highest diploid numbers for order Charadriiformes. This work analyzes for the first time the karyotype of Actitis macularius by classic cytogenetics and chromosome painting. Results: The species has a diploid number of 92, composed mostly of telocentric pairs. This high 2n is greater than the proposed 80 for the avian ancestral putative karyotype, suggesting that fission rearrangements have formed smaller macrochromosomes and microchromosomes. Fluorescence In Situ Hybridization using Burhinus oedicnemus whole chromosome probes confirmed these fissions in all pairs of macrochromosomes. Conclusion: Comparative analysis with other species of Charadriiformes studied by chromosome painting together with the molecular phylogenies for the order allowed us to raise hypotheses about the chromosomal evolution in suborder Scolopaci. From this, we can establish a clear idea of ​​how chromosomal evolution occurred in this suborder.
Efficacy-specific Herbal Group Detection from Traditional Chinese Medicine Prescriptions via Hierarchical Attentive Neural Network Model
Authors: Chen Li , Liu Xinglong , Zhang Siyuan , Yi Hong , Lu Yongmei , Yao Pan , Yu Zhonghua
Published: August 2020

Background: Mining massive prescriptions in Traditional Chinese Medicine (TCM) accumulated in the lengthy period of several thousand years to discover essential herbal groups for distinct efficacies is of significance for TCM modernization, thus starting to draw attentions recently. However, most existing methods for the task treat herbs with different surface forms orthogonally and determine efficacy-specific herbal groups based on the raw frequencies an herbal group occur in a collection of prescriptions. Such methods entirely overlook the fact that prescriptions in TCM are formed empirically by different people at different historical stages, and thus full of herbs with different surface forms expressing the same material, or even noisy and redundant herbs.Methods: We propose a two-stage approach for efficacy-specific herbal group detection from prescriptions in TCM. For the first stage we devise a hierarchical attentive neural network model to capture essential herbs in a prescription for its efficacy, where herbs are encoded with dense real-valued vectors learned automatically to identify their differences on the semantical level. For the second stage, frequent patterns are mined to discover essential herbal groups for an efficacy from distilled prescriptions obtained in the first stage.Results: We verify the effectiveness of our proposed approach from two aspects, the first one is the ability of the hierarchical attentive neural network model to distill a prescription, and the second one is the accuracy in discovering efficacy-specific herbal groups.Conclusion: The experimental results demonstrate that the hierarchical attentive neural network model is capable to capture herbs in a prescription essential to its efficacy, and the distilled prescriptions significantly could improve the performance of efficacy-specific herbal group detection.
Identification of SNP markers associated with antler growth rate in sika deer (Cervus nippon)
Authors: Hu Pengfei , Deng Yongyan , Ba Hengxing , li chunyi
Published: August 2020

Sika deer (Cervus nippon) constitutes one of the most valuable animal genetic resources in east Asia. The aim of this study was to identify and validate single nucleotide polymorphisms (SNPs) from antler growth-related genes of sika deer. The whole genome sequencing data of sika deer were used to identify SNP markers. Among them, 31 SNPs from antler growth-related genes exhibited significant polymorphism using genotyping by mass spectrometry. The observed and expected heterozygosities were ranged from 0.147 to 0.997 and 0.201 to 0.500, respectively. Significant deviation from the Hardy-Weinberg equilibrium was observed in 6 loci. These findings provide effective molecular detection markers for the study of variation in antler growth rate of sika deer.
Genome-Wide Identification and Functional Characterization of the PheE2F/DP Gene Family in Moso Bamboo
Authors: Li Long , Shi Qianqian , Gao Jian
Published: August 2020

Background
E2F/DP proteins have been shown to regulate genes implicated in cell cycle control and DNA repair. However, to date, research into the E2F/DP family and its functional role in Moso bamboo has been limited.
Results
Here, we identified 24 E2F/DP genes in the Moso bamboo genome, including nine E2F, six DP, and eight DEL genes. Simulation of the divergence time of paralogous gene pairs revealed an important role of whole-genome duplication in the expansion of the E2F/DP family. The regulatory element and coexpression network analysis indicated that E2F/DP regulated the expression of cell cycle-related genes. Yeast two hybrid assay and expression analysis based on transcriptome data and in situ hybridization indicated that PheE2F-PheDP complex play important roles in winter moso bamboo shoot growth. Expressional analysis based on qRT-PCR performed diverse expression patterns of PheE2F/DPs in response to both various abiotic stimuli and diurnal cycles.
Conclusion
These findings provide insights into the E2F/DP family members in Moso bamboo and experimental evidence for further functional verification of the E2F/DP family.
2D Crystalline Monolayer Nanosheets Produced from 1D-Amorphous Metal-Organic Framework
Authors: wang jiahui , Yang Pengfei , Liu Lingmei , Zheng Bin , Jiang Jing , Ma Jian-Ping , Yan Yi , Yang Song , Lin Bin , Liu Qi-kui , Han Yu , Chen Yin
Published: August 2020

MOFs are typical 3D crystalline materials, and amorphous MOFs emerges as a new attractive material family very recently. Herein, we report a novel layered MOF, IPM-1, which is synthesized from a cage-like organic linker with extremely weak interlaminar interaction. When subjected to external disturbance, IPM-1 degraded to an intermediate state between the crystalline and amorphous phase (1D-amorphours), in which the layers retain the in-plane two-dimension periodic structure but are misaligned in the third dimension, leading to the loss of apparent porosity and crystallinity. 1D-amorphous IPM-1 is readily exfoliated into crystalline 2D nanosheets with a thickness of 1.15 nm at gram-scale, excellent uniformity and homogeneity, lateral size up to 10 µm, and restored microporosity. They can fabricate wafer-scale thin films and present the first mass-producible 2D monolayer material. This work underlines that MOFs without apparent crystallinity can be idea precursors for the successful preparation of 2D crystalline monolayer nanosheets.
Classification of Sagittal Root Position and Angulation of Premolars for Immediate Implant Placement: A Cone Beam Computed Tomography Study
Authors: Zhan Yalin , Wang Miaozhen , Cheng Xueyuan , Liu Feng
Published: August 2020

Background: Sagittal root position (SRP) and thickness of buccal plate were of clinical guiding significance in implant treatment planning. The study was to classify the SRP and angulations of the maxillary and mandibular premolar to each osseous housing, and to measure the thickness of buccal plate by cone beam computed tomography (CBCT) in order to estimate the distributions and provide clinical decision support. Methods: CBCT images was reviewed on 150 patients who fulfilled the inclusion criteria. The sagittal root position and angulations of the maxillary and mandibular premolars to their respective osseous housing were evaluated and classified using CBCT images. The thickness of buccal plate at 1 mm, 3 mm, 5 mm apical to the alveolar crest was also measured. Results: The frequency distribution of SRP types indicated that, 41.67%, 51.83%, 3.67%, and 2.83% of maxillary premolars; 84.33%, 15%, 0%, and 0.67% of mandibular premolars were classified as type B, M, L, and N. The frequency distribution of angulation classifications indicated that, 20.83%, 46%, 32.17%, and 1% of maxillary premolars; 2%, 5.33%, 36.67%, and 56% of mandibular premolars were classified as class 1, 2, 3, and 4. The buccal bone thickness in most locations of premolar sites was less than 1 mm. Conclusions: The classification of clinical relevance of SRP and angulation of the premolar root to osseous housing would help for treatment planning and improving interdisciplinary communication of immediate implant placement (IIP) in the premolar region.
Nigella A ameliorates experimental colitis via interacting with gut microbiota on dextran sulphate sodium (DSS)-induced C57BL/6 mice
Authors: Hu XingJiang , Xu Nana , Yang Xi , Hu Xi , Zheng Yunliang , Zhang Qiao
Published: August 2020

Nigella A, also named Sieboldianoside A, has been extracted from many kinds of Traditional Chinese Medicine (TCM), such as Nigella glandulifera, Stauntonia chinensis DC., and the leaves of Acanthopanax sieboldianus. Nigella A exhibited potential analgesic, anti-inflammatory, anti-tumor, and antioxidant activities. However, whether Nigella A could treat ulcerative colitis (UC) is still unknown. As saponins always be regarded as the kinds of ingredients that could regulate immunity and intestinal flora. This research aimed to investigate the therapeutic effect of Nigella A on UC and explore its effect on intestinal flora. We noted that Nigella A and SASP could significantly improve the signs and symptoms, alleviate colonic pathological injury in DSS-induced mice. The changing of many specific bacterial genus such as Lactobacillus, Porphyromonadaceae, Bacteroides and Escherichia might closely related to the recovery of intestinal inflammatory response. This study initially confirmed the therapeutic effect of Nigella A and SASP on DSS-induced colitis by improving the diversity of intestinal microbial composition. Nigella A has the potential to be developed for the treatment of UC and other disorders related to the imbalance of intestinal flora.
Isolation and identification of a novel bacterium, Pseudomonas sp. ZyL-01, involved in the biodegradation of CL-20
Authors: Liu Zhiyong , Dang Kai , Li Cunzhi , Gao Junhong , Wang Hong , Gao Yongchao , Zhao Bin , Fan Peng , Qian Airong
Published: August 2020

Hexanitrohexaazaisowurtzitane (CL-20) is a compound with a polycyclic cage and an N-nitro group that has been shown to play an unfavorable role in several aspects, including environmental fate, biosafety, and physical health. The aim of this study was to isolate the microbial community and to identify a single microbial strain that can degrade CL-20 with desirable efficiency. Metagenomic sequencing methods were performed to investigate the dynamic changes in the composition of the community diversity. The most varied genus among the microbial community was Pseudomonas , which increased from 1.46% to 44.63% during the period of incubation (MC0–MC4). Furthermore, the new strain was isolated and identified from the activated sludge by bacterial morphological and 16s rRNA sequencing analyses. The CL-20 concentrations decreased by 75.21 μg/mL and 74.02 μg/mL in 48 h by MC4 and Pseudomonas sp. ZyL-01, respectively. However, the initial speed of CL-20 degradation by MC4 was more rapid than that by ZyL-01. Finally, a draft genome sequence was obtained to predict possible degrading enzymes involved in the biodegradation of CL-20. Specifically, 330 genes that are involved in energy production and conversion were annotated by Gene Ontology functional enrichment analysis, and some of these candidates may encode enzymes that are responsible for CL-20 degradation. In summary, our studies indicate that microbes might be a valuable biological resource for the treatment of environmental contamination caused by CL-20 and that Pseudomonas sp. ZyL-01 might be a promising candidate for eradicating CL-20 to achieve a more biosafe environment and improve public health.
Ovarian Function Preservation in Patients With Cervical Cancer Undergoing Hysterectomy and Ovarian Transposition Before Pelvic Radiotherapy
Authors: Jung Wonguen , Kim Yun Hwan , Kim Kyung Su
Published: August 2020

Background: To examine the factors associated with ovarian failure (OF) and assess the effectiveness of ovarian transposition (OT) before pelvic irradiation for preserving ovarian function in patients with cervical cancer (CC) undergoing hysterectomy.Methods: During 2003-2017, patients who underwent hysterectomy with preservation of one or both ovaries were retrospectively enrolled. Patients were divided into 4 groups, depending on whether radiotherapy (RT) and OT were performed: group 1, RT(+) and OT(+); group 2, RT(+) and OT(-); group 3, RT(-) and OT(+); group 4, RT(-) and OT(-). OF was defined as serum follicle-stimulating hormone levels of ≥30 mIU/mL.Results: Sixty-six patients (59 [89.4%] invasive CC and 7 [10.6%] cervical intraepithelial neoplasia) were included. The 2-year ovarian failure-free survival (OFFS) rate was 61.4% (95% confidence interval (CI) 37.8–86.0), 0%, 91.7% (95% CI 76.0–100), and 75.8% (95% CI 58.2–93.4) for groups 1, 2, 3, and 4, respectively. In groups 1 and 2 receiving RT, OT and combination of external beam radiotherapy and vaginal brachytherapy (VB) were associated with OF on multivariate analysis (MVA) (p-value=0.002 and 0.046, respectively). In groups 3 and 4 without RT, older age (40 years) and OT did not affect OF; however, the number of remaining ovaries was independently associated with OF in MVA (p=0.035).Conclusions: OT could effectively preserve ovarian function in adjuvant RT-treated patients. Lower location of transposed ovary with VB boost was significantly associated with early OF.
Management Practices of Emergency Departments in General Hospitals Based on Blockage of Chain of Infection during an COVID-19 Epidemic
Authors: Hu Xiaojing , Liu Si , Wang Bo , Xiong Hui , Wang Ping
Published: August 2020

In a coronavirus disease 2019 (COVID-19) epidemic, management of the emergency department is a difficult task in terms of prevention and control of the disease in general hospitals. On top of meeting urgent needs of patients for medical treatment, the emergency department also has to devote resources into investigation and prevention of COVID-19. At the beginning of the epidemic, with the strategy to intercept the chain of infection, Peking University First Hospital (PKUFH) focused on three important aspects: controlling the source of infection, cutting off the route of transmission, and protecting vulnerable populations, to expeditiously draft scientific and proper management measures for the emergency department, followed by real-time dynamic adjustments based on the development trend of the epidemic. These measures effectively ensured a smooth, orderly and safe operation of the emergency department. As of the writing of this manuscript, there has been no active COVID-19 infection in patients and medical staff in the emergency department, and no infection in patients admitted to PKUFH through the emergency department. This study describes the prevention and control measures in the emergency department of PKUFH during the outbreak of COVID-19, aiming to provide some reference for domestic and international medical institutions.
Identification of a gene signature closely related to immunosuppressive tumor microenvironment predicting prognosis of patients in EGFR mutant lung adenocarcinoma
Authors: Li Jia , Li Huahua , Zhang Chenyue , Zhang Chenxing , Wang Haiyong
Published: August 2020

Background: Lung adenocarcinomas (LUAD) harboring epidermal growth factor receptor (EGFR) mutations generally are unable to benefit from immune checkpoint inhibitors (ICIs), due to an immunosuppressive tumor microenvironment (TME) and a lower tumor mutation burden (TMB). Currently, there has been no gene signature that can comprehensively evaluate the TME and predict the prognosis of EGFR mutant LUAD patients. Methods: Using the cancer genome atlas (TCGA) database of EGFR mutant LUAD based on the immune score derived from the ESTIMATE algorithm, we screened the differential immune-related genes with prognostic value and compared the TMB profiles. Gene ontology (GO) and Kyoto encyclopedia of gene and genomic (KEGG) enrichment analysis were used to analyze the potential functions. The least absolute shrinkage and selectionator operator (LASSO) cox regression model was applied to identify a gene signature and constructed risk model. Kaplan-Meier survival and receiver operating characteristic (ROC) analysis were used to evaluate the prognostic value of the gene signature. CIBERSORT was used to evaluate the abundance of immune cells infiltration.Results: We screened 396 the differential immune-related genes based on immune score, whose potential functions were significantly related to T cell differentiation, immune response, cell cycle and cell proliferation. The disparities of TMB profile could be found between the high and low immune score group. Then, we identified a three-gene signature, including B and T lymphocyte attenuator (BTLA), BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) and centromere protein E (CENPE). The three-gene signature could well identify at-risk patients of EGFR-mutant LUAD patients in the training and validating set, and the high-risk patients were related to shorter overall survival (OS) (p=0.0053 and p=0.035). The immune activity of B cells and macrophages were higher in the low-risk group, in contrast the immune activity of Natural Killer (NK) cells and T cells were higher in the high-risk group. Conclusions: The three-gene signature closely related to immunosuppressive TME could predict risk prognosis of patients in EGFR mutant LUAD.
Fine and dynamic tuning the glycolytic flux ratio of an artificial carbon saving pathway for high yield of mevalonate in Escherichia coli
Authors: Li Ying , Xian He , Xu Ya , Zhu Yuan , Sun Zhijie , Wang Qian , Qi Qingsheng
Published: August 2020

Background In natural Escherichia coli, glucose is mainly metabolized via the Embden-Meyerhoff-Parnas (EMP) pathway. However, in the metabolic process of conversion of pyruvate to acetyl-CoA, one-third of the carbon is lost at CO2. To decrease the loss of glucose in the metabolic process and enhance the carbon conversion efficiency production of desired products by E. coli, we constructed a carbon saving pathway, EP-bifido pathway. As the balance of energy and reducing power was not optimal, we use synthetic biology methods to precisely and dynamically adjust the EMP pathway and pentose phosphate pathway (PPP) flux to improve the production of mevalonate (MVA) via the EP-bifido pathway. ResultHere, we enhanced the MVA titer and yield in E. coli in two ways. First, the promoter of the first gene of the PPP, zwf, was replaced with a set of promoters of different strength to enhance PPP flux for NADPH supply. Compared with the previous EP-bifido strains, the zwf-modified strains showed obvious differences in NADPH, NADH, and ATP synthesis levels and production routes. Among them, strain BP10BF accumulated 11.2 g/L of MVA after 72 h of fermentation and the molar conversion rate from glucose reached 62.2%. Second, the expression of pfkA was suppressed at a certain time by the clustered regularly interspaced short palindromic repeats interference (CRISPRi) system to avoid the growth defect caused by pfkA direct knock-out. The resulting MVA yield of strain BiB1F was 8.53 g/L, and the conversion rate from glucose reached 68.7%. ConclusionThis is the highest MVA conversion rate reported in shaken flask fermentation. The CRISPRi and promoter fine-tuning provided an effective strategy for metabolic flux redistribution in many metabolic pathways and promotes the chemicals production.
How a cardiovascular patient education system can be improved: Introducing a novel model for identifying hospital educational challenges and solutions
Authors: Saboktakin Atiyeh , Sepehri Mohammad Mehdi , Khasha Roghaye
Published: August 2020

Background: Cardiovascular diseases (CVDs) have always been considered by healthcare specialists for different reasons, including extensive prevalence, high cost, chronicity, and high risk of death. the recovery from CVDs is highly influenced by the behavior and lifestyle. As a result, it seems necessary to train and develop special abilities for patients and their companions, the development of efficient and effective training systems should be considered by healthcare specialists. Methods: Hence, in this study, an existing training system for cardiovascular patients is reviewed, and using field observation and targeted interviews with hospital experts, all aspects of its training process, including involved components, inputs, outputs, processes and interactions are extracted. Then the process maps of the training system are drawn up through the BPMN (Business Process Model and Notation) methodology. Next, its challenges and difficulties are identified with the aid of semi-structured interviews with experts, and due to the importance and different influence of the identified problems, these challenges are prioritized using the Multi Criteria Decision Making method (MCDM). Results: The most important identified challenges included high nursing workload and shortage of time, lack of understanding of training concepts by patients, lack of attention to training, disruption of training process by the patients’ companions, and patient's weakness in understanding the standard language. In identifying the root causes, learner, educator, and educational tools are the most effective in the training process; therefore, the improvement scenarios were designed accordingly. Conclusions: In the present study, a novel framework for cardiovascular patients' education has been designed and presented based on the analysis of the results of ranking the challenges and their root causes.
Enhancement of L-amino Acid Oxidase Production by Bacillus Subtilis H-8 With Oxygen-vector and Asymmetric Degradation of DL Arginine to D-arginine
Authors: xu peng , Pan Changpei , Cui Gongcheng , Wei ChunYan , Wang Lijuan , Li Yanting , Li Xiangping , Huang Shihai
Published: August 2020

The Bacillus subtilis H-8 independently screened by our laboratory can produce L-amino acid oxidase (L-AAO), and DL-arginine can be degraded asymmetrically by suspending the wet bacteria in the degradation liquid. By adding oxygen-vectors to the fermentation medium, the collected amount of wet bacteria can be increased. Taking n-dodecane, n-hexadecane, oleic acid, paraffin, and n-hexane as oxygen-vectors, the optimal oxygen-vector oleic acid was 1.2% (v/v). The weight of wet cells increased by 66.83% compared with before, and the activity of L-AAO in fermentation broth increased by 38.88% compared with before. The standard sample DL-arginine was derivatized by phenyl isothiocyanate, and then subjected to high performance liquid chromatography(HPLC), and the obtained peak area and arginine content were used as standard curves to measure the DL-arginine. The content of D-arginine and L-arginine in the initial degradation solution was 50% each, and the bacterial cells are added to the initial degradation solution of DL-arginine. After 21 hours of reaction, L-arginine was completely Degraded, remaining 47% of D-arginine.D-alanine was easily extracted from the reaction solution using cation-exchange resin,after centrifugation, decolorization, concentration and vacuum drying, and the chemical and optical purity of the extracted d-alanine was 92.68 and 97.46%, respectively.
Impact of Spinal Muscular Atrophy on Caregivers’ Daily Activities and Health-Related Quality of Life
Authors: Chen Er , Bawa Komal , Noone Josh , Whitmire Sarah , Buchenberger Daniel , Arnold William David , Mills Rosalina , Dixon Stacy
Published: August 2020

Background:Spinal muscular atrophy (SMA) is a genetic debilitating disease affecting approximately 10,000 individuals in the United States. Individuals with SMA frequently require caregiver support and care. Through a partnership with Cure SMA, we surveyed caregivers of individuals with SMA <18 years of age to understand the impact of SMA on caregivers with respect to their daily activities and health-related quality of life (HRQoL). In addition to structured questions, a standardized HRQoL instrument, the EQ-5D-5L and visual analogue scale, were administered.Results:The sample consisted of 45 unpaid caregivers of children with SMA. Of them, 22% reported that they were sole caregivers that received no additional caregiving support and 98% were parents of an affected individual. The majority of caregivers cared for individuals with type 2 (58%), followed by type 1 (38%) and type 3 (4%) SMA. Sixty-four percent of the individuals with SMA were able to sit without support or better, while 31% had some motor function and 5% reported no motor function. Across SMA types, caregivers reported spending a median 80 hours per month managing the overall care and treatment of the affected individual.. Most of the individuals (91%) were reported to have received nusinersen. Caregiver time investment correlated directly with disease severity measured by both SMA type and patient motor function level. The mean EQ-5D utility score for caregivers was 0.71 and their mean score on the EQ-5D visual analogue scale was 76. Specifically, 42% of caregivers reported any inability to do their usual activities and 73% reported any anxiety or depression.Conclusions:SMA negatively affects caregiver’s daily activities and HRQoL, representing a substantial burden. Disease severity is associated with an increasing amount of time required for care and support for patients with SMA and a decrease in a caregiver’s HRQoL. As treatments become available, evaluation of these treatments should include effects on the family as well.
Seasonal Variation of Nutritional Status and Oxidative Stress in Haemodialysis Patients - Are They Related?
Authors: Begovic Tanja Ilic , Radic Josipa , Radic Mislav , Modun Darko , Seselja-Perisin Ana , Tandara Leida
Published: August 2020

BackgroundSeasonal variations in body composition and parameters that reflect nutritional status are well established in haemodialysis (HD) patients. However, no study has assessed changes in oxidative stress (OS). The objectives of our study were to assess seasonal variations in OS, body composition and other nutritional parameters, as well as their interactions. MethodsSeasonal variations in fat tissue mass (FTM), fat tissue index (FTI), adipose tissue mass (ATM), lean tissue mass (LTM), lean tissue index, body cell mass (BCM and overhydration (OH), OS (the blood levels of derivatives of reactive oxygen metabolites (d-ROMs), thiobarbituric reactive substances (TBARS), plasma protein reduced thiol content (THIOLS) and ferric reducing ability of plasma (FRAP) were measured) and other nutritional parameters were assessed in 45 HD patients aged 70 (60.5-76.5) years. ResultsSignificantly increase in FTM (P=<0.001), FTI (P=<0.001) and ATM (P=<0.001) and significantly decrease in LTI (P=<0.001), LTM (P=<0.001), BCM (P=<0.001) and OH (P=0.004) over season was found. Also, significantly seasonal variations in d-ROMs (P=0.02) and THIOLS (P=0.02) were found. Statistically significant predictor of LTM and BCM was d-ROM (β =-0.57 (95% CI -1.08 to -0.06); P=0.03; β =-0.04 (95% CI -0.075 to -0.006); P=0.02). Furthermore, statistically most significant predictor of d-ROM was hip circumference (β =2.66 (95% CI 0.28 to 5.04); P=0.03), while for THIOLS it was WHtR (β=251(95% CI 16.6 to 477.2); P=0.03) and serum prealbumin level (β=263 (95% CI 6.8 to 521.1); P=0.04). ConclusionsThese results suggest seasonal variations of OS in HD patients and possible interaction between OS and nutritional status in HD patients.
Identification of a novel small nucleolar RNAs prognostic signature for patients with acute myelocytic leukemia
Authors: Huang Rui , Liao Xiwen , Li Qiaochuan
Published: August 2020

Background: This study mainly used The Cancer Genome Atlas (TCGA) RNA sequencing dataset to screen prognostic snoRNAs of acute myeloid leukemia (AML), and used for the construction of prognostic snoRNAs signature for AML. Methods: A total of 130 AML patients with RNA sequencing dataset were used for prognostic snoRNAs screenning. SnoRNAs co-expressed genes and differentially expressed genes (DEGs) were used for functional annotation, as well as gene set enrichment analysis (GSEA). Connectivity Map (CMap) also used for potential targeted drugs screening. Results:Through genome-wide screening, we identified 30 snoRNAs that were significantly associated with the prognosis of AML. Then we used the step function to screen a prognostic signature composed of 14 snoRNAs (SNORD72, SNORD38, U3, SNORA73B, SNORD79, SNORA73, SNORD12B, SNORA74, SNORD116-12, SNORA65, SNORA14, snoU13, SNORA75, SNORA31), which can significantly divide AML patients into high- and low-risk groups. Through GSEA, snoRNAs co-expressed genes and DEGs functional enrichment analysis, we screened a large number of potential functional mechanisms of this prognostic signature in AML, such as phosphatidylinositol 3-kinase-Akt ,Wnt, epithelial to mesenchymal transition, T cell receptors, NF-kappa B, mTOR and other classic cancer-related signaling pathways. In the subsequent targeted drug screening using CMap, we also identified six drugs that can be used for AML targeted therapy, they were alimemazine, MG-262, fluoxetine, quipazine, naltrexone and oxybenzone. Conclusion: Our current study was constructed an AML prognostic signature based on the 14 prognostic snoRNAs, which may serve as a novel prognostic biomarker for AML.
Non-invasive intra-uterine administration of Botulinum Toxin A enhances endometrial angiogenesis and improves the rates of embryo implantation
Authors: Koo Hwa Seon , Yoon Min-Ji , Hong Seon-Hwa , Ahn Jungho , Cha Hwijae , Lee Danbi , Park Chan Woo , Kang Youn-Jung
Published: August 2020

Background. Endometrial angiogenesis plays crucial roles in determining the endometrial receptivity. Defects in endometrial receptivity often cause repeated implantation failure, which is one of the major unmet needs for infertility and contributes a major barrier to the assisted reproductive technology. Despite the numerous extensive research work, there are currently no effective evidence-based treatments to prevent or cure this condition.Method. As a non-invasive treatment strategy, Botulinum toxin A (BoTA) was administered into one side of mouse uterine horns and saline was infused into the other side of horns for the control. Impact of BoTA was assessed in the endometrium at 3 or 8 days after infusion.Results. We demonstrated that BoTA administration enhances the capacity of endothelial cell tube formation and sprouting. The intrauterine BoTA administration significantly induced endometrial angiogenesis displaying increased numbers of vessel formation and expression levels of related-marker genes. Moreover, BoTA intrauterine application promoted the endometrial receptivity and the rates of embryo implantation were improved with BoTA treatment with no morphologically retarded embryos. Conclusion. Intrauterine BoTA treatment has a beneficial effect on vascular reconstruction of functional endometrium prior to embryo implantation by increasing endometrial blood flow near the uterine cavity suggesting BoTA treatment as a potential therapeutic strategy for patients who are suffering from repeated implantation failure with the problems with endometrial receptivity.
Under Fire –simultaneous Volatilome and Transcriptome Analysis Unravels Fine-scale Responses of Tansy Chemotypes to Dual Herbivore Attack
Authors: Clancy Mary V. , Haberer Georg , Jud Werner , Niederbacher Bishu , Niederbacher Simon , Senft Matthias , Zytynska Sharon , Weisser Wolfgang W. , Schnitzler Jörg-Peter
Published: August 2020

Background Tansy plants (Tanacetum vulgare L.) are known for their high intraspecific chemical variation, especially of volatile organic compounds (VOC) from the terpenoid group of substances. These VOCs are closely involved in plant-insect interactions and, when profiled, can be used to classify plants into groups known as chemotypes. Tansy chemotypes have been shown to influence plant-aphid interactions, however, to date no information is available on the response of different tansy chemotypes to simultaneous herbivory by more than one insect species. Results Using a multi-cuvette system, we investigated the responses of five tansy chemotypes to feeding by sucking and/or chewing herbivores (aphids and caterpillars; Metopeurum fuscoviride Stroyan and Spodoptera littoralis Boisduval). We did not observe any strong changes in plant VOC emissions when exposed to sucking aphids, while polyphagous caterpillars strongly increased VOC emissions for each plant chemotype. Herbivory by caterpillars following aphid infestation led to a plant chemotype-specific change in the patterns of terpenoids stored in trichome hairs and in VOC emissions. The transcriptomic analysis of a plant chemotype represents the first de novo assembly of a transcriptome in tansy and demonstrates priming effects of aphids on a subsequent herbivory. Overall, we show that the five chemotypes do not react in the same way to the two herbivores. As expected, we found that caterpillar feeding increased VOC emissions. However, the previous aphid infestation only led to a further increase in VOC emissions for some chemotypes. Conclusions We were able to show that different chemotypes respond to the double herbivore attack in different ways, and that pre-treatment with aphids had a priming effect on plants when they were subsequently exposed to a chewing herbivore. Our results will be important for the study of chemical communication of plants in nature. If neighbouring chemotypes in a field population react differently to herbivory/dual herbivory, this could possibly have effects from the individual level to the group level. Individuals of some chemotypes may respond more efficiently to herbivory stress than others, and in a group environment these "louder" chemotypes may affect the local insect community, including the natural enemies of herbivores, and other neighbouring plants.
Short-Term Physical Exercise Impacts On The Human Holobiont Obtained By A Randomised Intervention Study
Authors: Moitinho-Silva Lucas , Wegener Michelle , May Sandra , Schrinner Florian , Akhtar Awais , Boysen Teide Jens , Schaeffer Eva , Hansen Clint , Schmidt Timo , Ruehlemann Malte Christoph , Huebenthal Matthias , Rausch Philipp , Kondakci Mustafa T , Maetzler Walter , Weidinger Stephan , Laudes Matthias , Suess Philip , Schulte Dominik , Junker Ralf , Sommer Felix , Weisser Burkhard , Bang Corinna , Franke Andre
Published: August 2020

Background: Human well-being has been linked to the composition and functional capacity of the intestinal microbiota. As regular exercise is known to improve human health, it is not surprising that exercise was previously described to positively modulate the gut microbiota, too. However, most previous studies mainly focused on either elite athletes or animal models. Thus, we conducted a randomised intervention study that focused on the effects of different types of training (endurance and strength) in previously physically inactive, healthy adults in comparison to controls that did not perform regular exercise. Overall study duration was ten weeks including six weeks of intervention period. In addition to 16S rRNA gene amplicon sequencing of longitudinally sampled faecal material of participants (six time points), detailed body composition measurements and analysis of blood samples (at baseline and after the intervention) were performed to obtain overall physiological changes within the intervention period. Activity tracker devices (wrist-band wearables) provided activity status and sleeping patterns of participants as well as exercise intensity and heart measurements.Results: Different biometric responses between endurance and strength activities were identified, such as a significant increase of lymphocytes and decrease of mean corpuscular haemoglobin concentration (MCHC) only within the strength intervention group. In the endurance group, we observed a significant reduction in hip circumference and an increase in physical working capacity (PWC). Though a large variation of microbiota changes were observed between individuals of the same group, we did not find specific collective alterations in the endurance nor the strength groups, arguing for microbiome variations specific to individuals, and therefore, were not captured in our analysis. Conclusion: We could show that different types of exercise have distinct but moderate effects on the overall physiology of humans and very distinct microbial changes in the gut. The observed overall changes during the intervention highlight the importance of physical activity on well-being. Future studies should investigate the effect of exercise on a longer timescale, investigate different training intensities and consider high-resolution shotgun metagenomics technology.Trial registration: DRKS, DRKS00015873. Registered 12 December 2018; Retrospectively registered. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015873
Evaluating The Performance Of Malaysian Health Care Providers With Partial Least Squares Path Modeling
Authors: Salleh Mohd Idzwan Mohd , Abdullah Rosni , Zakaria Nasriah
Published: August 2020

Background: The Ministry of Health Malaysia invested significant resources to implement an electronic health record (EHR) system to ensure the full automation of hospitals for coordinated care delivery. Thus, evaluating whether the system has been utilized effectively is necessary, particularly on how it predicts the work performance of the health care providers. Methods: Convenience sampling was employed for data collection in three government hospitals for seven months. A standardized effectiveness survey for EHR systems was administered to health care providers (specialists, medical officers, and nurses) as they participated in medical education programs. Power analysis was conducted before and after the study to ensure adequate sample sizes and sufficient power. The empirical data was assessed by employing partial least squares-structural equation modeling for hypotheses testing. Results: As a results, knowledge quality had the highest score in predicting performance and had a large effect size, whereas system compatibility became the strongest component of system quality. The findings indicated that EHR systems supported the clinical tasks and workflows of care providers, which increased system quality, whereas increased quality of knowledge improved user performance. Conclusion: Therefore, knowledge quality and effective use should be incorporated into the evaluation study of EHR system effectiveness in health institutions. Data mining feature can be integrated into current systems for generating health populations and disease trend analysis easily and systematically, therefore improving clinical knowledge of care providers and effective use to maintain their productivity. The validated survey instrument can be further tested with empirical surveys in other public and private hospitals with different interoperable EHR systems.
Global model for uneven illumination enhancement of document images
Authors: Hakim Moad , Bella Fatim Zahra Ait , Mourabit Idriss El , Raghay Said
Published: August 2020

Exponential growth of low-cost digital imagery is latterly observed. Images acquired under uneven lighting are prone to experience poor visibility, which may severely limit the performance of most computational photography and automatic visual recognition applications. Different from current optimization techniques, we design a novel partial differential equation based model to rectify the variable illumination artifacts. In this study, a large number of document samples capturing uneven illumination and low contrast conditions are tested to compare the effectiveness of the proposed local and nonlocal approaches. The suggested algorithm can be applied in Arabic, Latin and Chinese document images with any type of shade.
Two ancient genome duplication events shape diversity in Hibiscus L. (Malvaceae)
Authors: Eriksson Jonna Sofia , Bacon Christine D. , Bennett Dominic J. , Pfeil Bernard E. , Oxelman Bengt , Antonelli Alexandre
Published: August 2020

Background: The great diversity in plant genome size and chromosome number is partly due to polyploidization (i.e., genome doubling events). The differences in genome size and chromosome number among diploid plant species can be a window into the intriguing phenomenon of past genome doubling that may be obscured through time by the process of diploidization. The genus Hibiscus L. (Malvaceae) has a wide diversity of chromosome numbers and an allegedly complex genomic history. Hibiscus is ideal for exploring past genomic events because although two ancient genome duplication events have been identified, as more are still likely to be found, considering its diverse background. To reappraise the group’s genomic history, we tested a series of scenarios describing different polyploidization events using previously identified duplications in Hibiscus syriacus.Results: The data showed that >54% of the single-copy genes where in fact paralogues. When testing for different genome duplication scenarios using gene count data; species of Hibiscus was shown to have shared one genome duplication with H. syriacus, -- while one whole genome duplication was contained within H. syriacus, -- to be the preferred model given the observed distribution of paralogous gene copies in Hibiscus.Conclusions: Here, we corroborated the independent genome doubling previously found in the lineage leading to H. syriacus and a shared genome doubling of this lineage and the remainder of Hibiscus. Additionally, we found a previously undiscovered genome duplication shared by the /Pavonia and /Malvaviscus clades (both nested within Hibiscus) with the occurrences of two copies in what were otherwise single-copy genes. Our results highlight the complexity of genomic diversity in some plant groups, which makes orthology assessment and accurate phylogenomic inference difficult.
Mesenchymal stem cells regulated liver DX5- natural killer cells in acute-on-chronic liver failure
Authors: Xiong Jing , Weng Weizhen , Lin Dengna , Cao Huijuan , Chen Junfeng , Zhang Shaoquan , Zhang Jing , Gao Juan , Gyory Ildiko , Gao Zhiliang , Xiong Shiqiu , Lin Bingliang
Published: August 2020

Background :Acute-on-chronic liver failure (ACLF) is a severe, life-threatening syndrome with high mortality. Transplantation of Mesenchymal Stem Cells (MSCs) have been shown their efficacy in reducing mortality of ACLF patients in our clinical trials. Unveiling the underlying mechanism of action will improve clinical regime of ACLF. Methods: Flow cytometry was applied to assess frequency and phenotype of peripheral blood natural killer cell (NK) from HBV-ACLF patients during MSCs treatment. An acute-on-chronic liver failure mouse model was established by injection of carbon tetrachloride (CCL4) intraperitoneally. We used flow cytometry to characterize frequency, phenotype, proliferation, cytokine secretion and cell conjugation of NK cells from different sources before and after MSCs treatment. Microscopy was applied to investigate cell-cell contact. Results: Frequency of peripheral blood NK cells from HBV-ACLF patients was upregulated by MSCs infusion, which correlated with hepatitis remission. MSCs infusion rescued ACLF mice efficiently, coinciding with hepatitis remission, liver regeneration and NK cells frequency increase both in blood and liver. Strikingly, NKP46+ DX5-, instead of NKP46+ DX5+ liver NK cells responded well to MSCs. In vitro, MSCs were proved to promote the proliferation and GM-CSF secretion of NKP46+ DX5- liver NK cells specifically, which may be owing to their high cell-cell adhesion. Conclusions: Promoting NKP46+ DX5- liver NK cells proliferation and secreting GM-CSF maybe the new machinery of MSCs’ efficacy in ACLF.