bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced PRL-1 expression in placenta-derived mesenchymal stem cells accelerates hepatic function via mitochondrial dynamics in a cirrhotic rat model
Authors: Kim Jae Yeon , Choi Jong Ho , Jun Ji Hye , Park Sohae , Jung Jieun , Bae Si Hyun , Kim Gi Jin
Published: September 2020

Background: Placenta-derived mesenchymal stem cells (PD-MSCs) have been highlighted as an alternative cell therapy agent that has become a next-generation stem cell treatment. Phosphatase of regenerating liver-1 (PRL-1), an immediate early gene, plays a critical role during liver regeneration. Here, we generated enhanced PRL-1 in PD-MSCs (PD-MSCsPRL-1, PRL-1+) using lentiviral and nonviral gene delivery systems and investigated mitochondrial functions by PD-MSCPRL-1 transplantation for hepatic functions in a rat bile duct ligation (BDL) model.Methods: PD-MSCsPRL-1 were generated by lentiviral and nonviral AMAXA gene delivery systems and analyzed for their characteristics and mitochondrial metabolic functions. Liver cirrhosis was induced in Sprague-Dawley (SD) rats using common BDL for 10 days. PKH67+ naïve and PD-MSCsPRL-1 were intravenously administered into cirrhotic rats using a nonviral system (2x106 cells/animal). The animals were sacrificed at 1, 2, 3, and 5 weeks after transplantation and engraftment of stem cells, and histopathological analysis and hepatic mitochondrial functions were performed.Results: PD-MSCsPRL-1 were successfully generated using lentiviral and nonviral AMAXA systems and maintained characteristics similar to those of naïve cells. Compared with naïve cells, PD-MSCsPRL-1 improved respirational metabolic states of mitochondria. In particular, mitochondria in PD-MSCsPRL-1 generated by the nonviral AMAXA system showed a significant increase in the respirational metabolic state, including ATP production and mitochondrial biogenesis (*p<0.05). Furthermore, transplantation of PD-MSCsPRL-1 using a nonviral AMAXA system promoted engraftment into injured target liver tissues of a rat BDL cirrhotic model and enhanced the metabolism of mitochondria via increased mtDNA and ATP production, thereby improving therapeutic efficacy.Conclusions: Our findings will further our understanding of the therapeutic mechanism of enhanced MSCs and provide useful data for the development of next-generation MSC-based cell therapy and therapeutic strategies for regenerative medicine in liver disease.
Illuminating the dark side of the human transcriptome with long read transcript sequencing
Authors: Kuo Richard , Cheng Yuanyuan , Zhang Runxuan , Brown John W.S. , Smith Jacqueline , Archibald Alan L. , Burt Dave W.
Published: September 2020

Background: The human transcriptome annotation is regarded as one of the most complete of any eukaryotic species. However, limitations in sequencing technologies have biased the annotation toward multi-exonic protein coding genes. Accurate high-throughput long read transcript sequencing can now provide additional evidence for rare transcripts and genes such as mono-exonic and non-coding genes that were previously either undetectable or impossible to differentiate from sequencing noise. Results: We developed the Transcriptome Annotation by Modular Algorithms (TAMA) software to leverage the power of long read transcript sequencing and address the issues with current data processing pipelines. TAMA achieved high sensitivity and precision for gene and transcript model predictions in both reference guided and unguided approaches in our benchmark tests using simulated Pacific Biosciences (PacBio) and Nanopore sequencing data and real PacBio datasets. By analyzing PacBio Sequel II Iso-Seq sequencing data of the Universal Human Reference RNA (UHRR) using TAMA and other commonly used tools, we found that the convention of using alignment identity to measure error correction performance does not reflect actual gain in accuracy of predicted transcript models. In addition, inter-read error correction can cause major changes to read mapping, resulting in potentially over 6K erroneous gene model predictions in the Iso-Seq based human genome annotation. Using TAMA’s genome assembly based error correction and gene feature evidence, we predicted 2,566 putative novel non-coding genes and 1,557 putative novel protein coding gene models.Conclusions: Long read transcript sequencing data has the power to identify novel genes within the highly annotated human genome. The use of parameter tuning and extensive output information of the TAMA software package allows for in depth exploration of eukaryotic transcriptomes. We have found long read data based evidence for thousands of unannotated genes within the human genome. More development in sequencing library preparation and data processing are required for differentiating sequencing noise from real genes in long read RNA sequencing data.
Peritumoral ductular reaction can be a prognostic factor for intrahepaticcholangiocellular carcinoma
Authors: Shen Zhenyang , Xiao Jingbo , Wang Junjun , Lu Lungen , Wan Xinjian , Cai Xiaobo
Published: September 2020

Background: Peritumoral ductular reaction (DR) was reported to be related to the prognosis of combined hepatocellular-cholangiocarcinoma and hepatocellular carcinoma. Non-mucin-producing intrahepatic cholangiocarcinoma (ICC) which may be derived from small bile duct cells or liver progenitor cells (LPCs) was known to us. However, whether peritumoral DR is also related to non-mucin-producing ICCs remains to be investigated. Methods: Forty-seven patients with non-mucin-producing ICC were eventually included in the study and clinicopathological variables were collected. Immunohistochemical analysis and immunofluorescence staining for cytokeratin 19, proliferating cell nuclear antigen, and α-smooth muscle actin were performed in tumor and peritumor liver tissues.Results: A significant correlation existed between peritumoral DR and local inflammation and fibrosis. (r = 0.357, 95% CI, 0.037-0.557; P = 0.008 and r = 0.742, 95% CI, 0.580-0.849; P < 0.001, respectively). Patients with obvious peritumoral DR had high recurrence rate (81.8% vs 56.0%, P = 0.058) and poor overall and disease-free survival time (P = 0.01 and P = 0.03, respectively) comparing with mild peritumoral DR. Compared with the mild peritumoral DR group, the proliferation activity of LPCs/ cholangiocytes was higher in obvious peritumoral DR, which, however, was not statistically significant. (0.43±0.29 vs 0.28±0.31, P = 0.172). Furthermore, the correlation analysis showed that the DR grade was positively related to the portal/septalα-SMA level (r = 0.359, P = 0.001).Conclusions: Peritumoral DR was associated with local inflammation and fibrosis. Patients with non-mucin-producing ICC having obvious peritumoral DR had a poor prognosis. Peritumoral DR could be a prognostic factor for ICC. However, the mechanism should be further investigated.
Genome-wide small RNA profiling reveals tiller development in tall fescue (Festuca arundinacea Schreb.)
Authors: Hu Tao , Wang Tao , Li Huiying , Wassie Misganaw , Xu Huawei , Chen Liang
Published: September 2020

Background: Tall fescue (Festuca arundinacea Schreb.) is a major cool-season forage and turfgrass species. The low tiller density and size dramatically limits its turf performance and forage yield. MicroRNAs (miRNA)-genes modules play critical roles in tiller development in plants. In this study, a genome-wide small RNA profiling was carried out in two tall fescue genotypes contrasting for tillering production (‘Ch-3’, high tiller production rate and ‘Ch-5’, low tiller production rate) and two types of tissue samples at different tillering development stage (Pre-tillering, grass before tillering; Tillering, grass after tillering). ‘Ch-3’, ‘Ch-5’, Pre-tillering, and Tillering samples were analyzed using high-throughput RNA sequencing. Results: A total of 222 million high-quality clean reads were generated and 208 miRNAs were discovered, including 148 known miRNAs belonging to 70 families and 60 novel ones. Furthermore, 18 miRNAs were involved in tall fescue tiller development process. Among them, 14 miRNAs displayed increased abundance in both Ch-3 and Tillering plants compared with that in Ch-5 and Pre-tillering plants and were positive with tillering, while another four miRNAs were negative with tiller development. Out of the three miRNAs osa-miR156a, zma-miR528a-3p and osa-miR444b.2, the rest of 15 miRNAs were newfound and associated with tiller development in plants. Based on our previous full-length transcriptome analysis in tall fescue, 2 8927 potential target genes were discovered for all identified miRNAs. Most of the 212 target genes of the 18 miRNAs were dominantly enriched into “ubiquitin-mediated proteolysis”, “phagosome”, “fatty acid biosynthesis”, “oxidative phosphorylation”, and “biosynthesis of unsaturated fatty acids” KEGG pathways. In addition, bdi-miR167e-3p targets two kinase proteins EIF2AK4 and IRAK4, and osa-miR397a targets auxin response factor 5, which may be the significant miRNA-genes controllers in tillering development. Conclusions: This is the first genome-wide miRNA profiles analysis to identify regulators involved in tiller development in cool-season turfgrass. Tillering related 18 miRNAs and their 212 target genes provide novel information for the understanding of the molecular mechanisms of miRNA-genes mediated tiller development in cool-season turfgrass.
Reliability of Echocardiographic Measurements in Infants Exposed to Zika Virus.
Authors: Orofino Dulce Helena Gonçalves , Passos Sonia Regina Lambert , Leite Maria de Fatima Moreira Pereira , Farias Carla Verona Barreto , Ramos Thiago Moreira , Silva Leticia Machado Lima e , Oliva Raffaela Andrade , Oliveira Raquel de Vasconcellos Carvalhaes
Published: September 2020

Background: Ecocardiography is currently the gold standard imaging method for the diagnosis of most congenital and acquired cardiopathies and for the evaluation of myocardial function and cardiac chamber size and overload. Ecocardiographic measures of left ventricular and right ventricular structure and function are used to define ventricular function and guide medical decisions.The objective of this study is to assess the reproducibility of echocardiographic cardiac chamber measurements in infants in utero exposed to Zika virus. Methods: Masked cross-sectional diagnostic study with two independent measurements of cardiac chamber dimensions using echocardiography. We studied 50 infants with in utero exposure to Zika virus ranging from 30 to 270 days old of the outpatient clinic of a national reference center for maternal and child health, Rio de Janeiro, Brazil.The analysis included the measurements of the aortic root, left atrium, end diastolic left ventricle, systolic left ventricule, left ventricular ejection fraction, ventricular end diastolic septal thickness, end diastolic thickness of the left ventricular posterior wall and right ventricule. Bland-Altman plots were used to explore differences. Agreement according to intraclass correlation coefficients (ICC) was interpreted as follows: excellent≥0.75, fair to good 0.4≤ICC<0.75, and poor with ICC<0.4. Results: All parameters had mean difference of diameters near to zero, excluding left ventricule ejection fraction. Ventricular end-diastolic septal thickness and end-diastolic-thickness of the left ventricular posterior wall showed few unique mean values. Reproducibility was excellent for the aortic root and end diastolic left ventricule (ICC=0.86 and 0.91, respectively), fair/good to poor for other parameters and the left ventricule ejection fraction, ventricular end diastolic septal thickness and the end diastolic thickness of the left ventricular posterior wall showed the lowest reproducibility (ICC=0.46,0.37,0.53, respectively). Conclusions: The minor divergences did not affect the echocardiography results in our sample. However, caution is required to interpret results of measures with low reproducibility.
Factors Influencing the Result of Superior Oblique Weakening Procedures in Patients with Superior Oblique Overaction in Horizontal Strabismus
Authors: Chun Junwoo , Kim Seong-Joon
Published: September 2020

Background: Few studies have evaluated the surgical outcome of superior oblique weakening procedures in patients with superior oblique overaction associated with exotropia or esotropia. This study aimed to evaluate the outcome of superior oblique muscle weakening and the influencing factors in patients with superior oblique overaction.Methods: The medical charts of 37 patients (55 eyes) with superior oblique overaction associated with esotropia or exotropia who were treated with a superior oblique weakening procedure at the Seoul National University Hospital from January 2010 to June 2017 were retrospectively reviewed. Superior oblique overaction was graded using, a 6-point scale ranging from +0.5 to +3, and pre- and postoperative grades were recorded for all patients. Results: The mean age of the patients was 91.81 ± 59.37 months. Superior oblique muscle suture spacer and superior oblique posterior tenectomy were performed for 17 (23 eyes) and 20 (32 eyes) patients, respectively. Surgical success was achieved in 15 (65.2%) eyes in the suture spacer group and 23 (71.9%) eyes in the posterior tenectomy group. Surgical success was achieved for 69.1% (38/55 eyes) of patients. Dissociated vertical deviation exhibited a significant negative association with the surgical success rate (p<0.001).Conclusions: There was no significant difference in surgical success rate between the superior oblique posterior tenectomy and superior oblique suture spacer groups in superior oblique overaction associated with horizontal strabismus. Associated dissociated vertical deviation can affect the surgical success of the superior oblique weakening procedure.
Two-year outcomes after full-thickness astigmatic keratotomy combined with small-incision lenticule extraction for high astigmatism
Authors: Kim Bu Ki , Chung Young Taek
Published: September 2020

Background: To evaluate clinical outcomes after full-thickness astigmatic keratotomy (FTAK) combined with small-incision lenticule extraction (SMILE) in eyes with high astigmatism.Methods: This study comprised 75 eyes of 43 patients with over 4.0 diopters (D) of astigmatism who were treated with SMILE after FTAK. Visual acuities and refractive measurements were evaluated at 1 month after FTAK, and 1, 6, 12, and 24 months after SMILE. Vector analysis of the astigmatic changes was performed using the Alpins method.Results: Twenty-four months after the combined procedure, the average spherical equivalent was reduced from -6.56 ± 2.38 D to -0.36 ± 0.42 D (p < 0.001). The uncorrected and corrected distance visual acuities improved from 1.54 ± 5.53 to -0.02 ± 0.09 and from -0.03 ± 0.07 D to -0.07 ± 0.08 D (both p < 0.001), respectively. The preoperative mean astigmatism was -5.48 ± 1.17 D, which was reduced to -2.27 ± 0.97 D and -0.34 ± 0.26 D at 1 month after FTAK and 24 months after SMILE, respectively (p <0.001). The surgically-induced astigmatism after FTAK, SMILE, and FTAK and SMILE combined was 3.38 ± 1.18 D, 2.22 ± 0.84 D, and 5.39 ± 1.20 D, respectively. Furthermore, the correction index of FTAK, SMILE, and FTAK and SMILE combined was 0.63 ± 0.17, 0.90 ± 0.40, and 0.98 ± 0.06, respectively. There were no intraoperative or postoperative complications. Conclusion: Our surgical procedure combining FTAK and SMILE showed good and stable clinical outcomes during two-year follow-up for the treatment of high astigmatism.
Prospective study on a fast-track training in psychiatry for medical students: The Psychiatric Hat Game
Authors: Clément Anthony , Delage Raphaël , Chollier Marie , Josse Laure , Gaudry Stéphane , Zahar Jean-Ralph , Baubet Thierry , Degos Bertrand
Published: September 2020

Background: While medical students are losing interest in lectures in favor of other educational materials, many studies suggest the benefit of active learning, combined with gamified educational tools. The authors developed a psychiatric adaptation of the « Hat Game ». It was hypothesised that this game would increase both knowledge and motivation in medical students toward psychiatric semiology. The aim of the study was to assess the benefit of a Psychiatric Hat Game session for learning psychiatric symptoms in third-year medical students. Student performance was also evaluated at 3 months.Methods: This gamified fast-track training consisted of two teams and each team must guess as many psychiatric semiology terms as possible using different techniques (i.e. speech, mime). The study involved a pre- and post-evaluation of knowledge (Multiple Choice Questions) and a satisfaction survey. Baseline, post-immediate, and three-months scores were compared by using Friedman analysis for paired samples. Comparisons of mean scores at two different times were performed by using Wilcoxon test for paired samples.Results: Knowledge mean scores were significantly higher after the game than before (+ 28.6%, p < 0.001). Improvement was maintained three months after the game (+ 18.9%, p < 0.001). Satisfaction survey items highlighted that students enjoyed and would recommend this type of gamified training.Conclusions: The Psychiatric Hat Game improved knowledge of psychiatric semiology in medical students. Results suggest that it is a promising and efficient tool to playfully teach medical semiology, with transferable features, utility and acceptability from one medical field to another. This study contributes to the growing body of knowledge advocating for serious games and gamified training in medical education.
Autopsy and Informatics Analysis Evidence Coagulopathy Progress in COVID-19 Patients
Authors: Jiang Tiebin , Lv Bo , Liu Hongxia , He Shiwen , Zhang Guogang , Li Chanyi , Li Wanqiong , Li Weilin , He Yaqi , Zhang Tong , Wang Yunyun , Mo Wu , Yi Ning , Peng Luying , Li Ying , Ruan Chunhong , Li Chengyuan , Liu Yaqi , Luo Peipei , Jiang Huan , Xue Zhigang , Liu Liang , Wang Wenjun
Published: September 2020

Background
The outbreak of COVID-19 around the world resulted in more than 480 thousand deaths.
Objective
To clarify the thrombotic phenomena with coagulation progress in COVID-19 patients based on epidemiological statistics combining the autopsy and informatics analysis.
Methods
Using 9 autopsy results with COVID-19 pneumonia and the medical records of 407 patients including 39 deceased ones whose discharge status was certain, time-sequential changes of 11 coagulation relevant indices within mild, severe and critical infection throughout hospitalization according to NHC guidelines were evaluated. Informatics tools were applied to calculate the importance and correlation between them and the progression of thrombosis.
Results
At the beginning of the hospitalization, PLT had a significant decrease in critically ill patients. GLU, PT, APTT, and D-dimer in critical patients were higher than those in mild and severe during the whole admission period. The ISTH DIC score also showed the continuous overt DIC in critical patients. At the late stage of non-survivors, the dynamic profiles of PLT, PT, and D-dimer were significantly different from survivors. A random forest model indicated that the most important feature was PT, followed by D-dimer, indicating their crucial roles for the progression of disease.
Conclusions
COVID-19 is constantly spreading wildly around the world, combining autopsy data, time-sequential profiles and informatics methods to explore the dynamic changes of coagulation relevant indices throughout the course of the disease deterioration, which helps guide the therapy and detect the prognosis in different level of COVID-19 infection.
Identification of co-existence of Alport syndrome and C3 glomerulonephritis in a proband with family history
Authors: Ding Yin , Tang Xuanli , Du Yuanyuan , Chen hongyu , Yu Dongrong , Zhu Bin , Yuan Bohan
Published: September 2020

Background

Alport syndrome and C3 glomerulonephritis (C3GN) are rare kidney diseases, frequently responsible for familial haematuria, proteinuria, and renal impairment. With the rapid development of molecular genetic testing, Alport syndrome causes have been restricted mostly to variants in the COL4A5 or COL4A3/COL4A4 genes. Moreover, a broad range of genetic contributors in the complement and complement-regulating proteins are definitely implicated in the pathogenesis of C3GN.

Methods

We sought a family with persistent microscopic haematuria associated with renal failure. Clinicopathologic and follow-up data were obtained, and molecular genetic testing was used to screen for pathogenic variants.

Results

We describe a three-generation family with Alport syndrome showing a dominant maternal inheritance. Notably, renal biopsy showed the concurrent histological evidence of C3GN in the proband harbouring a rare heterozygous variation in CFHR5 , c.508G>A. The alteration leads to replacement of a highly conserved residue at position 170 of the β-strand subunit of CFHR5 (p.Val170Met). In silico analysis showed that the variation was predicted to deregulate complement activation by altering the structural properties and enhancing C3b binding capacity to compete with Complement Factor H (CFH), which was in line with experimental data previously published.

Conclusions

The comorbidity findings between Alport syndrome and C3GN indicate an underlying overlap and require further study.
Exogenous melatonin enhances salt secretion from salt glands by upregulating the expression of ion transporter and vesicle transport genes in Limonium bicolor
Authors: Li Junpeng , Yuan Fang , Liu Yanlu , Zhang Mingjing , Liu Yun , Zhao Yang , Wang Baoshan , Chen Min
Published: September 2020

Background: Salt, a common environmental stress factor, inhibits plant growth and reduces yields. Melatonin is a pleiotropic molecule that regulates plant growth and can alleviate environmental stress in plants. All previous research on this topic has focused on the use of melatonin to improve the relatively low salt tolerance of glycophytes by promoting growth and enhancing antioxidant ability. It is unclear whether exogenous melatonin can increase the salt tolerance of halophytes, particularly recretohalophytes, by enhancing salt secretion from the salt glands. Results: To examine the mechanisms of melatonin-mediated salt tolerance, we explored the effects of exogenous applications of melatonin on the secretion of salt from the salt glands of Limonium bicolor (a kind of recretohalophyte) seedlings and on the expression of associated genes. A pretreatment with 5 μM melatonin significantly improved the growth of L. bicolor seedlings under 300 mM NaCl. Furthermore, exogenous melatonin significantly increased the dry weight and endogenous melatonin content of L. bicolor. In addition, this treatment reduced the content of Na+ and Cl– in leaves, but increased the K+ content. Both the salt secretion rate of the salt glands and the expression level of genes encoding ion transporters (LbHTK1, LbSOS1, LbPMA, and LbNHX1) and vesicular transport proteins (LbVAMP721, LbVAP27, and LbVAMP12) were significantly increased by exogenous melatonin treatment. These results indicate that melatonin improves the salt tolerance of the recretohalophyte L. bicolor via the upregulation of salt secretion by the salt glands.Conclusions: Our results showed that melatonin can upregulate the expression of genes encoding ion transporters and vesicle transport proteins to enhance salt secretion from the salt glands. Combining the results of the current study with previous research, we formulated a novel mechanism by which melatonin increases salt secretion in L. bicolor. Ions in mesophyll cells are transported to the salt glands through ion transporters located at the plasma membrane. After the ions enter the salt glands, they are transported to the collecting chamber adjacent to the secretory pore through vesicle transport and ions transporter and then are secreted from the secretory pore of salt glands, which maintain ionic homeostasis in the cells and alleviate NaCl-induced growth inhibition.
RNA-seq reveals tight junction-relevant erythropoietic fate induced by OCT4 in human hair follicle mesenchymal stem cells
Authors: Yu Xiaozhen , Sun Pengpeng , Huang Xingang , Chen Hua , Huang Weiqing , Ruan Yingchun , Jiang Weina , Tan Xiaohua , Liu Zhijing
Published: September 2020

Background: Human hair follicle mesenchymal stem cells (hHFMSCs) isolated from hair follicles possess multilineage differentiation potential. OCT4 is a gene critically associated with pluripotency properties. The cell morphology and adhesion of hHFMSCs significantly changed after transduction of OCT4 and two subpopulations emerged, including adherent cells and floating cell. Floating cells cultured in hematopoietic induction medium and stimulated with erythropoetic growth factors could transdifferentiate into mature erythrocytes, whereas adherent cells formed negligible hematopoietic colonies. The aim of this study was to reveal the role of cell morphology and adhesion on erythropoiesis induced by OCT4 in hHFMSCs and to characterize the molecular mechanisms involved.Methods: Floating cell were separated from adherent cell by centrifugation of the upper medium during cell culture. Cell size was observed through flow cytometry and cell adhesion was tested by disassociation and adhesion assays. RNA sequencing was performed to detect genome-wide transcriptomes and identify differentially expressed genes. GO enrichment analysis and KEGG pathway analysis were performed to analysis the functions and pathways enriched by differentially expressed genes. The expression of tight junction core members was verified by qPCR and Western blot. A regulatory network was constructed to figure out the relationship between cell adhesin, cytoskeleton, pluripotency and hematopoiesis.Results: The overexpression of OCT4 influenced the morphology and adhesion of hHFMSCs. Transcripts in floating cells and adherent cells are quite different. Data analysis showed that upregulated genes in floating cells were mainly related to pluripotency, germ layer development (including hematopoiesis lineage development), and downregulated genes were mainly related to cell adhesion, cell junctions and the cytoskeleton. Most molecules of the tight junction (TJ) pathway were downregulated and molecular homeostasis of the TJ was disturbed, as CLDNs were disrupted, and JAMs and TJPs were upregulated. The dynamic expression of cell adhesion-related gene E-cadherin and cytoskeleton-related gene ACTN2 might cause different morphology and adhesion. Finally, a regulatory network centered to OCT4 was constructed, which elucidated that he TJ pathway critically bridges pluripotency and hematopoiesis in a TJP1-dependent way.Conclusions: Regulations of cell morphology and adhesion via the TJ pathway conducted by OCT4 might modulate hematopoiesis in hHFMSCs, thus developing potential mechanism of erythropoiesis in vitro.
Association between Economic Development Level and Tuberculosis Registered Incidence in Shandong,China
Authors: Zhang Qianyun , Yang Dongmei , Cao Linqing , Liu Jinyue , Tao Ningning , Li Yifan , Liu Yao , Song Wanmei , Xu Tingting , Li Shijin , An Qiqi , Liu Siqi , Gao Lei , Song Wanyan , Li Huaichen
Published: September 2020

Background : Tuberculosis (TB) is one of the major infectious diseases that seriously endanger people's health.In Shandong province, the relationship between the level of economic development and TB incidence has not been studied.This study aims to provide more research basis for the government to prevent and control TB by exploring the impact of different economic factors on TB incidence. Methods : By constructing threshold regression model (TRM),we described the extent to which different economic factors contribute to TB registered incidence and differences in TB registered incidence among seventeen cities with different levels of economic development in Shandong province, China, during 2006-2017. Data were retrieved from the China Information System for Disease Control and Prevention. Results: Per capita medical expenditure（regression coefficient，-0.0314462；SD，0.0079305；P>|t|，0.000）and per capita savings（regression coefficient，0.0001924；SD，0.0000566；P>|t|，0.001） passed the significance test at the level of 1%.They are the two economic indicators that have the greatest impact on TB registered incidence.Through the threshold test, we selected the per capita savings as the threshold variable.In the three stages of per capita savings(＜9772.8086 China Yuan(CNY)；9772.8086 - 33835.5391 CNY；＞33835.5391 CNY), rural per capita income always has a significant negative impact on the TB registered incidence (The regression coefficients are -0.0015682, -0.0028132 and -0.0022253 respectively.P is 0.007,0.000 and 0.000 respectively.).In cities with good economies,TB registered incidence was 38.30% in 2006 and dropped to 25.10% by 2017. In cities with moderate economies, TB registered incidence peaked in 2008 at 43.10% and dropped to 27.1% by 2017.In poorer cities, TB registered incidence peaked in 2008 at 56.30% and dropped to 28.9% in 2017. Conclusion: We found that per capita savings and per capita medical expenditure are most closely related to the TB incidence. Therefore, relevant departments should formulate a more complete medical system and medical insurance policy to effectively solve the problem of "difficult and expensive medical treatment". In order to further reduce the TB incidence, in addition to timely and accurate diagnosis and treatment, it is more important for governments to increase investment in medicine and health care.
Response inhibition alterations in migraine: Evidence from event-related potentials and evoked oscillations
Authors: Chen Guoliang , Li Yansong , Dong Zhao , Wang Rongfei , Zhao Dengfa , Obeso Ignacio , Yu Shengyuan
Published: September 2020

Background: Migraine is characterized by a hypersensitivity to environmental stimulation which climaxes during headache attacks but persists during attack-free period. Despite ongoing debates about the nature of the mechanisms giving rise to this abnormality, the presence of deficient inhibitory cortical processes has been proposed to be one possible mechanism underlying its pathogenesis. Empirical evidence supporting this claim is mainly based on previous accounts showing functional cortical disexcitability in the sensory domain. Considering that a general inhibitory control process can play an important role across early to later stage of information processing, this may indicate the important role other dimensions of inhibitory control can play in migraine disability. The present study examined the pathophysiological features of inhibitory control that takes place during suppression of prepotent responses in migraineurs. Methods: Twenty-two patients with migraine without aura (mean age = 30.86 ± 5.69 years; 19 females) during the interictal period and 25 healthy controls (mean age = 30.24 ± 3.52 years; 18 females) were recruited. We used a stop signal task in combination with event-related potentials (ERPs) to examine participants’ neural activity supporting response inhibition. Results: Behaviorally, migraineurs exhibited prolonged stop signal reaction times relative to healthy controls. At the neural level, the amplitude of the stop-N2 over fronto-central, central and centro-parietal scalp regions, a component of the ERPs related to conflict monitoring during early, non-motoric stages of inhibition, was significantly increased in migraineurs. Meanwhile, the amplitude of the stop-P3 over central and centro-parietal scalp regions, a component of the ERPs reflecting late-stage inhibition of the motor system and cognitive evaluation of motor inhibition, was also significantly increased in migraineurs. Ultimately, our time-frequency analysis further revealed increased delta activity in migraineurs. Conclusions: Consistent with the theory that alterations in cognitive cortical processes are a key signature of migraine, our findings revealed an abnormal state of suppressing prepotent responses in migraineurs, which can be attributed to cortical disexcitability of the pre-frontal executive network and centro-parietal sensorimotor network. These novel findings extend to show the existence of dysfunctional inhibition control that occurs during suppression of prepotent responses in migraneurs.nctional inhibition control that occurs during suppression of prepotent responses in migraneurs.
Detecting Land Use Modification And Its Influence on Resident Communities
Authors: Endalew Tesfahun Admas
Published: September 2020

Background

The study intended to detecting the land use land cover changes, trends and their magnitude between 1986 and 2019 years by using GIS and remote sensing in Fagita Lekoma District, Amhara region, Ethiopia. Three satellite data set of Landsat Thematic Mapper for 1986, Enhanced Thematic Mapper Plus for 2002 and Operational Land Imager for 2019 were used generate land use and land cover maps of the study area. Post classification comparison changed detection method was employed to identify gains and losses between Land Use Land Cover classes. Socioeconomic survey, key informant interview and field observation were also used conclude the encouragement of land use /land cover change in the study area.
Results

The result shows that cultivated land and wetland similarly decline in the entire study periods. In the 33 years, forest lands expanded by upon 200% of the original forest cover what was existed on the base year. Whereas, a result of the socioeconomic analysis the expansion of Acacia decurrens tree plantations and agricultural land are main causes of land use land cover change in the study area. The impact of this land use land cover change is more significant on the livelihood condition and status of the study area.
Conclusion

The land use system of the study area highly converted cultivation land into forest/tree plantation. Mainly, the expansion of Acacia decurrens tree plantation on farmland is increasing the income of local residence when compare with the previous living condition in the study area.
Broad Spectrum Epidemiological Contribution of Cannabis and Other Substances to the Teratological Profile of Northern New South Wales: Geospatial and Causal Inference Analysis
Authors: Reece Albert Stuart , Hulse Gary Kenneth
Published: September 2020

Background: Whilst cannabis commercialization is occurring rapidly guided by highly individualistic public narratives, evidence that all congenital anomalies (CA) increase alongside cannabis use in Canada, a link with 21 CA’s in Hawaii, and rising CA’s in Colorado indicate that transgenerational effects can be significant and impact public health. It was therefore important to study Northern New South Wales (NNSW) where cannabis use is high. Methods: Design: Cohort. 2008-2015. Setting: NNSW and Queensland (QLD), Australia. Participants. Whole populations. Exposures. Tobacco, alcohol, cannabis. Source: National Drug Strategy Household Surveys 2010, 2013. Main Outcomes. CA Rates. NNSW-QLD comparisons. Geospatial and causal regression. Results: Cardiovascular, respiratory and gastrointestinal anomalies rose with falling tobacco and alcohol but rising cannabis use rates across Queensland. Maternal age NNSW-QLD was not different (2008-2015: 4265/22084 v. 96473/490514 >35 years/total, Chi.Sq.=1.687, P=0.194). A higher rate of NNSW cannabis-related than cannabis-unrelated defects occurred (prevalence ratio (PR)=2.13, 95%C.I. 1.80-2.52, P=3.24x10-19). CA’s rose more potently with rising cannabis than with rising tobacco or alcohol use. Exomphalos and gastroschisis had the highest NNSW:QLD PR (6.29(2.94-13.48) and 5.85(3.54-9.67)) and attributable fraction in the exposed (84.11%(65.95-92.58%) and 82.91%(71.75-89.66%), P=2.83x10-8 and P=5.62x10-15). In multivariable geospatial models cannabis was significantly linked with cardiovascular (atrial septal defect, ventricular septal defect, tetralogy of Fallot, patent ductus arteriosus), genetic (chromosomal defects, Downs syndrome), gastrointestinal (small intestinal atresia), body wall (gastroschisis, diaphragmatic hernia) and other (hypospadias) (AVTPCDSGDH) CA’s. In linear modelling cannabis use was significantly linked with anal stenosis, congenital hydrocephalus and Turner syndrome (ACT) and was significantly linked in borderline significant models (model P<0.1) with microtia, microphthalmia, and transposition of the great vessels. At robust and mixed effects inverse probability weighted multivariable regression cannabis was related to 18 defects. 16/17 E-Values in spatial models were >1.25 ranging up to 5.2x1013 making uncontrolled confounding unlikely. Conclusions: These results suggest that population level CA’s react more strongly to small rises in cannabis use than tobacco or alcohol; cardiovascular, chromosomal, body wall and gastrointestinal CA’s rise significantly with small increases in cannabis use; that cannabis is a bivariate correlate of AVTPCDSGDH and ACT anomalies, is robust to adjustment for other substances; and is causal.
Hospitalized COVID-19 Patients treated with Convalescent Plasma in a Mid-size City in the Midwest
Authors: Hartman William R , Hess Aaron S , Connor Joseph P
Published: September 2020

BackgroundSARS-CoV-2 and its associated disease, COVID-19, has infected over seven million people world-wide, including two million people in the United States. While many people recover from the virus uneventfully, a subset of patients will require hospital admission, some with intensive care needs including intubation, and mechanical ventilation. To date there is no cure and no vaccine is available. Passive immunotherapy by the transfusion of convalescent plasma donated by COVID-19 recovered patients might be an effective option to combat the virus, especially if used early in the course of disease. Here we report our experience of using convalescent plasma at a tertiary care center in a mid-size, midwestern city that did not experience an overwhelming patient surge. Methods Hospitalized COVID-19 patients categorized as having Severe or Life-Threatening disease according to the Mayo Clinic Emergency Access Protocol were screened, consented, and treated with convalescent plasma collected from local donors recovered from COVID-19 infection. Clinical data and outcomes were collected retrospectively. Results 31 patients were treated, 16 severe patients and 15 life-threatened patients. Overall mortality was 27% (4/31) but only patients with life-threatening disease died. 94% of transfused patients with severe disease avoided escalation to ICU care and mechanical ventilation. 67% of patients with life-threatening disease were able to be extubated. Most transfused patients had a rapid decrease in their respiratory support requirements on or about day 7 following convalescent plasma transfusion. ConclusionOur results demonstrate that convalescent plasma is associated with reducing ventilatory requirements in patients with both severe and life-threatening disease, but appears to be most beneficial when administered early in the course of disease when patients meet the criteria for severe illness.
Noise2Atom: Unsupervised Denoising for Scanning Transmission Electron Microscopy Images
Authors: Wang Feng , Henninen Trond R , Keller Debora , Erni Rolf
Published: September 2020

We propose an effective deep learning model to denoise scanning transmission electron microscopy (STEM) image series, named Noise2Atom, to map images from a source domain S to a target domain C, where S is for our noisy experimental dataset, and C is for the desired clear atomic images. Noise2Atom uses two external networks to apply additional constraints from the domain knowledge. This model requires no signal prior, no noise model estimation, and no paired training images. The only assumption is that the inputs are acquired with identical experimental configurations. To evaluate the restoration performance of our model, as it is impossible to obtain ground truth for our experimental dataset, we propose consecutive structural similarity (CSS) for image quality assessment, based on the fact that the structures remain much the same as the previous frame(s) within small scan intervals. We demonstrate the superiority of our model by providing evaluation in terms of CSS and visual quality on different experimental datasets.
Cigarette Smoking Reduces BDNF in Heavy Smokers
Authors: Miladpour Behnoosh , Mohammadian Farideh , Kavousipour Soudabeh , Alimardani Parvaneh , Tavassoli Alireza
Published: September 2020

Background: Cigarette smoke is a powerful environmental modifier of DNA methylation. BDNF is a neurotrophin family of growth factors and is important in growth, progression, regeneration, survival, maintenance, and function of neurons. In this study, we aimed to evaluate the epigenetic changes, serum level, and gene expression of BDNF, in cigarette smokers. Methods: To assess the BDNF DNA methylation, peripheral blood samples were obtained from 237 cigarette smokers and 90 healthy nonsmokers as controls. DNA methylation was evaluated with MS-PCR. Gene expression and serum level were carried out with qRT-PCR and ELISA assay respectively. Results: The results from MS-PCR showed that DNA methylation of BDNF gene is more significant in heavy smokers than healthy nonsmokers as control (p-value <0.05). Serum level of BDNF and gene expression is significantly lower in heavy smokers than in healthy nonsmokers (p-value <0.05). Conclusion: In conclusion, heavy smoking can modify BDNF gene epigenetics. The serum levels of BDNF and the gene expression decreases in heavy smokers compared to healthy nonsmokers.
Super-enhancer Associated Long Non-coding RNA AC005592.2 Promotes Tumor Progression by Regulating OLFM4 in Colorectal Cancer
Authors: Yan Linping , Chen Huanhuan , Tang Li , Jiang Pan , Yan Feng
Published: September 2020

Background: Super-enhancer-associated long non-coding RNAs (SE-lncRNAs) have been reported to play essential roles in tumorigenesis, but the fundamental mechanism of SE-lncRNAs in colorectal cancer (CRC) remains largely unknown. Methods: A microarray was performed to identify the differentially expressed SE-lncRNAs between CRC tissues and peritumoral tissues. A novel SE-lncRNA AC005592.2 was selected from these differentially expressed SE-lncRNAs to explore its effects in the CRC development. Fluorescence quantitative real-time PCR (qRT-PCR) was used to assay the expression of AC005592.2 in CRC tissues and cell lines. Functional assays were applied to identify the biological effects of AC005592.2 in CRC cells. Furthermore, RNA-seq was employed to predict potential targets of AC005592.2. Results: AC005592.2 was significantly increased in CRC tissues and cells. And the high expression of AC005592.2 was significantly associated with TNM stage and tumor differentiation of CRC patients. Knockdown of AC005592.2 suppressed CRC cell proliferation, invasion and migration, but promoted apoptosis, while AC005592.2 overexpression exerted precisely the opposite effects on CRC cells. Besides, AC005592.2 positively regulated the expression of olfactomedin 4 (OLFM4), which was also up-regulation in CRC tissues. Conclusion: The findings suggested that AC005592.2 is a crucial promoter of CRC progression, and may serve as an attractive therapeutic target for CRC.
Machine Learning based Tissue Analysis Reveals Brachyury has a Diagnosis Value in Breast Cancer
Authors: Li Kaichun , Wang Qiaoyun , Lu Yanyan , Pan Xiaorong , Liu Long , Cheng Shiyu , Wu Bingxiang , Song Zongchang , Gao Wei
Published: September 2020

Background The aim of this study was to confirm the role of Brachyury in breast cells and to establish and verify whether four types of machine learning models can use Brachyury expression to predict the survival of patients.Methods We conducted a retrospective review of the medical records to obtain patient information, and made the patient's paraffin tissue into tissue chips for staining analysis. We selected a total of 303 patients for research and implemented four machine learning prediction algorithms, including multivariate logistic regression model, decision tree, artificial neural network and random forest, and compared the results of these models with each other. Area under the receiver operating characteristic (ROC) curve (AUC) was used to compare the results.Results The chi-square test results of relevant data suggested that the expression of Brachyury protein in cancer tissues was significantly higher than that in paracancerous tissues (p=0.0335); breast cancer patients with high Brachyury expression had a worse overall survival (OS) compared with patients with low Brachyury expression. We also found that Brachyury expression was associated with ER expression (p=0.0489). Subsequently, we used four machine learning models to verify the relationship between Brachyury expression and the survival of breast cancer patients. The results showed that the decision tree model had the best performance (AUC=0.781).Conclusions Brachyury is highly expressed in breast cancer and indicates that the patient had a poor chance of survival. Compared with conventional statistical methods, decision tree model shows superior performance in predicting the survival status of breast cancer patients. This indicates that machine learning can thus be applied in a wide range of clinical studies.
A novel thermostable alkaline histamine oxidase from Glutamicibacter sp. N1A310, induced by histamine and its analogue betahistine
Authors: Sadeghi Hossein , Arjmand Sareh , Siadat Seyed Omid Ranaei , Fooladi Jamshid , Ebrahimipour Gholamhossein
Published: September 2020

Biogenic amines (BAs) are low molecular weight organic bases formed by natural amino acids decarboxylation and trigger an array of toxicological effects in humans and animals. Bacterial amine oxidases enzymes are determined as practical tools to implement the rapid quantification of BAs in foods. Our study set out to obtain a new efficient, amine oxidase enzyme for developing new enzyme-based quantification of histamine. The soils from different sources were screened using histamine as sole carbon and nitrogen sources, and histamine oxidase producing bacteria were selected and identified using specific primers for histamine oxidase (HOD) gene. The HOD gene of six strains, out of 26 isolated histamine-utilizing bacteria, were amplified using our designed primers. The HOD enzyme from Glutamicibacter sp. N1A3101, isolated from nettle soil, was found to be thermostable and showed the highest substrate specificity toward the histamine and with no detected activity in the presence of putrescine, cadaverine, spermine, and spermidine. Its oxidation activity toward tyramine was lower than other HOD reported so far. The isolated enzyme was stable at 60 °C for 30 min and showed pH stability ranging from 6-9. Furthermore, we indicated the induction of identified HOD activity in the presence of betahistine as well, with nearly equal efficiency and without the consumption of the substrate.