bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytokine Dysregulation Persists in Childhood Post Neonatal Encephalopathy
Authors: Zareen Zunera , Strickland Tammy , Eneaney Victoria Mc , Kelly Lynne A. , McDonald Denise , Sweetman Deirdre , Molloy Eleanor J.
Published: February 2020

Background: Cytokines are possible mediators of neuroinflammation and associated with adverse outcome in neonatal encephalopathy (NE) . Our aim was to explore cytokine response in children with Neonatal Encephalopathy (NE) at school age compared to age-matched controls.
Method: Follow up at school age, children who had NE and age-matched controls were assessed for their cytokine responses and neurodevelopment outcome. Pro- and anti-inflammatory cytokines in the serum, [Interleukin (IL)-1α, IL-1β, IL-2, IL-6, IL-8, IL-18, Tumor necrosis factor (TNF)-α, TNF β, Interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), erythropoietin (EPO), IL-10 & IL-1RA] were measured at baseline and in response to in vitro stimulation with lipopolysaccharide (LPS: endotoxin).
Results: GM­-CSF, TNF-β, IL-2 IL-6 and IL-8 were significantly elevated at school age following NE (n=40) compared to controls (n=37). A rise in GM-CSF, IL-8, TNF-α, IL-1β, & IL-6 were seen in NE group following LPS stimulation. Relative LPS hypo-responsiveness was also noted in children with severe NE with IL-10, VEGF, EPO and TNF-β. Elevated TNF-β was associated with low gross motor scores on assessment at school age.

Conclusion: School-age children post-NE had significantly altered cytokine responses to endotoxin compared to controls. TNF-β was associated with adverse developmental outcomes. This suggests the inflammatory process may persist into childhood and a longer therapeutic window may be available for neuroprotection therapies.
Spatio-temporal dynamics of EEG features during sleep in major depressive disorder after treatment with escitalopram: A pilot study
Authors: Wu Li , Wang Xue-Qin , Yang Yong , Dong Teng-Fei , Lei Ling , Cheng Qi-Qi , Li Su-Xia
Published: February 2020

Background: Previous studies have shown escitalopram is related to sleep quality. However, effects of escitalopram on dynamics of electroencephalogram (EEG) features especially during different sleep stages have not been reported. This study may help to reveal pharmacological mechanism underlying escitalopram treatment.Methods: The spatial and temporal responses of patients with major depressive disorder (MDD) to escitalopram treatment were analyzed in this study. Eleven MDD patients and eleven healthy control subjects who completed eight weeks’ treatment of escitalopram were included in the final statistics. Six-channel sleep EEG signals were acquired during sleep. Power spectrum and nonlinear dynamics were used to analyze the spatio-temporal dynamics features of the sleep EEG after escitalopram treatment. Results: For temporal dynamics: after treatment, there was a significant increase in the relative energy (RE) ofA band (0.5 - 2Hz), accompanied by a significant decrease in the RE ofb band (20 - 30Hz). Lempel-Ziv complexity and Co - complexity values were significantly lower. EEG changes at different sleep stages also showed the same regulation as throughout the night sleep. For spatio dynamics: after treatment, the EEG response of the left and right hemisphere showed asymmetry. Regarding band-specific EEG complexity estimations, δ1 and β2 in stage-1 and δ1 in stage-2 sleep stage in frontal cortex is found to be much more sensitive to escitalopram treatment in comparison to central and occipital cortices.Conclusions: The sleep quality of MDD patients improved, EEG response occurred asymmetry in left and right hemispheres due to escitalopram treatment, and frontal cortex is found to be much more sensitive to escitalopram treatment. These findings may contribute to a comprehensive understanding of the pharmacological mechanism of escitalopram in the treatment of depression.
Value of digital mammography in predicting lymphovascular invasion of breast cancer
Authors: Liu Zhuangsheng , Li Ruqiong , Liang Keming , Chen Junhao , Chen Xiangmeng , Li Xiaoping , Li Ronggang , Zhang Xin , Yi Lilei , Long Wansheng
Published: February 2020

Background: Lymphovascular invasion (LVI) has never been revealed by preoperative scans. It is necessary to use digital mammography in predicting LVI in patients with breast cancer preoperatively. Methods: Overall 122 cases of invasive ductal carcinoma diagnosed between May 2017 and September 2018 were enrolled and assigned into the LVI positive group (n = 42) and the LVI negative group (n = 80). Independent t-test and χ2 test were performed. Results: Difference in Ki-67 between the two groups was statistically significant (P = 0.012). Differences in interstitial edema (P=0.013) and skin thickening (P=0.000) were statistically significant between the two groups. Multiple factor analysis showed that there were three independent risk factors for LVI: interstitial edema (odds ratio [OR] = 12.610; 95% confidence interval [CI]: 1.061-149.922; P=0.045), blurring of subcutaneous fat (OR = 0.081; 95% CI: 0.012-0.645; P = 0.017) and skin thickening (OR = 9.041; 95% CI: 2.553-32.022; P = 0.001). Conclusions: Interstitial edema, blurring of subcutaneous fat, and skin thickening are independent risk factors for LVI. The specificity of LVI prediction is as high as 98.8% when the three are used together.
Telomere Length in Patients with Transfusion-Dependent Thalassemia
Authors: Nanthatanti Nithita , Tantiworawit Adisak , Piriyakhuntorn Pokpong , Rattanathammethee Thanawat , Hantrakool Sasinee , Chai-Adisaksopha Chatree , Rattarittamrong Eakarat , Norasetthada Lalita , Tuntiwechapikul Wirote , Fanhchaksai Kanda , Charoenkwan Pimlak , Kumfu Sirinart , Chattipakorn Nipon
Published: February 2020

Background: Thalassemia is a hereditary hemolytic anemia with a severity ranging from mild, non-transfusion dependent to severe chronic anemia requiring lifelong transfusion. Transfusional iron overload is a major complication in patients with transfusion-dependent thalassemia (TDT). Telomeres are sequences of nucleotides forming the end caps of chromosomes that act as a DNA repair system. Iron overload in thalassemia can cause increased oxidative stress which leads to cellular damage and senescence. This may result in telomere length shortening. The degree of telomere length shortening may reflect the severity of thalassemia. Methods: This research aimed to study the telomere length in patients with TDT in comparison to non-thalassemic individuals and to identify the clinical and laboratory parameters that are associated with telomere length. We conducted a cross-sectional study in patients with TDT aged ³18 years. Telomere length was measured by real-time quantitative PCR. Results: Sixty-five patients with TDT were enrolled onto the study. There were 37 female patients (54.4%). The median age was 27 (18-57) years, and mean pre-transfusion hemoglobin (Hb) was 7.1 (± 1.07) g/dL. The mean telomere terminal restriction fragment (TRF) length of patients with TDT and the controls was 6.11 (± 0.61) kb and 6.79 (± 0.84) kb, respectively (p <0.0001). There was a significant correlation between telomere TRF length and age (p =0.0002), and Hb (p=0.044). There was no correlation of telomere length with other factors. Conclusions: Our study showed that TDT patients had shorter telomere length compared with controls. Telomere shortening in TDT was an aging-dependent process and associated with lower hemoglobin level.
Identification of the regulatory networks and hub genes controlling alfalfa floral pigmentation variation using RNA-sequencing analysis
Authors: Duan Hui-Rong , Wang Li-Rong , Cui Guang-Xin , Zhou Xue-Hui , Duan Xiao-Rong , Yang Hongshan
Published: February 2020

Background: To understand the gene expression networks controlling flower color formation in alfalfa, flowers anthocyanins were identified using two materials with contrasting flower colors, namely Defu and Zhongtian No. 3, and transcriptome analyses of PacBio full-length sequencing combined with RNA sequencing were performed, across four flower developmental stages.
Results: Malvidin and petunidin glycoside derivatives were the major anthocyanins in the flowers of Defu, which were lacking in the flowers of Zhongtian No. 3. The two transcriptomic datasets provided a comprehensive and systems-level view on the dynamic gene expression networks underpinning alfalfa flower color formation. By weighted gene coexpression network analyses, we identified candidate genes and hub genes from the modules closely related to floral developmental stages. PAL , 4CL , CHS , CHR , F3’H , DFR , and UFGT were enriched in the important modules. Additionally, PAL6 , PAL9 , 4CL18 , CHS2 , 4 and 8 were identified as hub genes. Thus, a hypothesis explaining the lack of purple color in the flower of Zhongtian No. 3 was proposed.
Conclusions: These analyses identified a large number of potential key regulators controlling flower color pigmentation, thereby providing new insights into the molecular networks underlying alfalfa flower development.
Lentivirus expressing shRNAs inhibit the replication of Contagious Ecthyma virus by targeting DNA polymerase gene
Authors: Samani Leila Asadi , saffar behnaz , Mokhtari Azam , Arefian Ehsan
Published: February 2020

Background: Contagious ecthyma or Orf is known as a zoonotic disease remains prevalently worldwide despite the application of some control strategies against it. RNAi particularly shRNA provides us with the chance to tackle this obstacle by an encouraging new approach. The current study indicates the design and experiment of third-generation lentivirus packaging systems delivering shRNAs to inhibit Orf virus (ORFV) replication and infection. Given the importance of DNA-pol gene in virus replication, in this study, three shRNAs against this gene were designed and cloned into lentiviral vectors to stabilize the expression of shRNAs. After producing lentivectors expressing ORFV-DNA– pol in HEK293T cells, the synthesized shRNAs were applied to downregulate viral replication and gene expression. The reduction in viral titer and RNA was evaluated by TCID50 test as well as real-time RT-PCR. The results were then analyzed in comparison with the control group. Results: Designed shRNAs significantly reduced virus yield approximately 90% to 97% and 96.8% to 99.4%, respectively compared to the control groups (cells infected with ORFV and infected with ORFV and scrambled vector) by TCID50 test. Real-time RT-PCR revealed a dramatic reduction in the expression of viral RNA approximately 99% compared to cells infected with ORFV and from 92.6% to 99%, respectively compared to cells infected with ORFV and scrambled vector. Conclusions: Therefore, it can be stated that RNAi is capable of being used as a potent therapeutically option against viruses like ORFV.
The effect of improved housing on indoor mosquito density and exposure to malaria in the rural community of Minkoameyos, Centre Region of Cameroon.
Authors: Nguela Rachel Laure , Bigoga Jude D. , Armel Tedjou N. , Esther Tallah Tayie Ngobiyo , Dongmo Line Leukou , Boris Njeambosay A. , Frederic Tchouine , Kazi Riksum , Williams Peter , Mbacham Wilfred F. , Leke Rose G. F.
Published: February 2020

Background This study evaluated the effectiveness of improved housing on indoor residual mosquito density and exposure to malaria-carrying anophelines in Minkoameyos, a rural community in southern forested Cameroon. Methods Following the identification of housing factors affecting malaria prevalence in 2013, 218 houses were improved by screening the doors and windows, installing plywood ceilings on open eaves and closing holes on walls and doors. Monthly entomological surveys were conducted in a sample of 21 improved and 21 non-improved houses from November 2014 to October 2015. Mosquitoes sampled from night collections on human volunteers were identified morphologically and their parity status determined. Mosquito infectivity was verified through Plasmodium falciparum CSP ELISA and the average entomological inoculation rates determined. A Reduction Factor (RF), defined as the ratio of the values for mosquitoes collected outdoor to those collected indoor was calculated in improved houses (RFI) and non-improved houses (RFN). An Intervention Effect (IE=RFI/RFN) measured the true effect of the intervention. Chi-square test was used to determine variable significance. The threshold for statistical significance was set at P < 0.05. Results A total of 1113 mosquitoes were collected comprising Anopheles sp (58.6%), Culex sp (36.4%), Aedes sp (2.5%), Mansonia sp (2.4%) and Coquillettidia sp (0.2%). Amongst the anophelines were An. gambiae s.l. (95.2%), An. funestus (2.9%), An. ziemanni (0.2%), An. brohieri (1.2%) and An. paludis (0.5%). An. gambiae s.s. was the only Anopheles gambiae siblings found. The intervention reduced the indoor Anopheles density by 1.8 folds (RFI=3.99; RFN=2.21; P=0.001 ). The indoor density of parous Anopheles reduced by 1.7 folds (RFI=3.99; RFN=2.21; P=0.04 ) and that of infected Anopheles by 1.8 folds (RFI=3.26; RFN=1.78; P=0.04 ). Indoor peak biting rates were observed between 02am to 04am in non-improved houses and from 02am to 06am in improved houses. Conclusion Housing improvement contributed to reducing indoor residual anopheline density and malaria transmission. This highlights the need for policy specialists to further evaluate and promote aspects of house design as a complementary control tool that could reduce indoor human–vector contact and malaria transmission in similar epidemiological settings.
Characterisation of proliferation, differentiation potential, and gene expression among clonal cultures of human dental pulp cells
Authors: Kobayashi Tomoko , Torii Daisuke , Iwata Takanori , Izumi Yuichi , Nasu Masanori , Tsutsui Takeo W.
Published: February 2020

The authors have withdrawn the journal submission associated with this preprint and requested that the preprint also be withdrawn.
Methicillin-resistant Staphylococcus aureus nasal colonization among HIV-infected patients in Taiwan: prevalence, molecular characteristics and associated factors with nasal carriage
Authors: Hsu Yi-Yu , Wu David , Hung Chien-Ching , Huang Shie-Shian , Yuan Fang-Hsueh , Lee Ming-Hsun , Huang Ching-Tai , Shie Shian-Sen , Huang Po-Yen , Yang Chien-Chang , Cheng Chun-Wen , Leu Hsieh-Shong , Wu Ting-Shu , Huang Yhu-Chering
Published: February 2020

Objective To evaluate nasal carriage, antibiotic susceptibility and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA), as well as the risk factors of MRSA colonization, in human immunodeficiency virus (HIV)-infected patients in northern Taiwan. Methods From September 2014 to November 2015, HIV-infected patients seeking outpatient care at four hospitals were eligible for this study. A nasal specimen was obtained from each subject for the detection of S. aureus and a questionnaire was completed by each subject. MRSA isolates once identified were characterized. Results Of 553 patients surveyed, methicillin-susceptible S. aureus (MSSA) was detected in 119 subjects (21.5%) and MRSA in 19 subjects (3.4%). Female gender, injection drug use, smoking, hepatitis C virus carrier, cancer and antibiotic use within one year were positively associated with MRSA colonization. By multivariate analysis, only cancer (adjust odds ratio (aOR) 7.78, [95% confidence interval (CI), 1.909-31.731]) and antibiotic use within one year (aOR 3.89, [95% CI, 1.219-12.433]) were significantly associated with MRSA colonization. Ten isolates were characterized as sequence type (ST) 59/staphylococcal chromosome cassette (SCC) IV or V T , endemic community strains in Taiwan, four isolates as ST 8/SCC mec IV (USA 300) and one isolate as ST 239/SCC mec IIIA, a hospital strain. All the community-associated MRSA isolates were susceptible to trimethoprim-sulfamethoxazole (TMP-SMX). Conclusions Nasal MRSA carriage in HIV-infected patients seeking outpatient care was low (3.4%) in northern Taiwan. Most of the colonizing isolates were genetically endemic community strains and exhibited high susceptibility to TMP-SMX and fluoroqinolones. Cancer and antibiotic use within one year were associated with MRSA colonization.
Implementation of the WHO Hand Hygiene Strategy in Faranah Regional Hospital, Guinea
Authors: Müller Sophie Alice , Diallo Alpha Oumar Karim , Wood Rebekah , Bayo Mouctar , Eckmanns Tim , Tounkara Ousmane , Arvand Mardjan , Diallo Mamadou , Borchert Matthias
Published: February 2020

Background: Healthcare-associated infections are the most frequent adverse events in healthcare worldwide, with limited available evidence suggesting highest burden in resource-limited settings. Recent Ebola epidemics emphasize the disastrous impact that spread of infectious agents within healthcare facilities can have, accentuating the need for improvement of infection control practices. Hand hygiene (HH) measures are considered to be the most effective tool to prevent healthcare-associated infections. However, HH knowledge and compliance are low, especially in vulnerable settings such as Guinea.

The aim of PASQUALE (Partnership to Improve Patient Safety and Quality of Care) was to assess knowledge and compliance with HH and improve HH by incorporating the WHO HH Strategy within the Faranah Regional Hospital (FRH), Guinea.

Methods: In a participatory approach, a team of FRH staff and leadership was invited to identify priorities of the hospital prior to the start of PASQUALE. The local hygiene committee was empowered to increase its activities and take ownership of the HH improvement strategy. A baseline assessment of knowledge, perception and compliance was performed months before the intervention. The main intervention consisted of local alcohol-based-hand-rub (ABHR) production, with final product efficacy testing, in conjunction with a training adapted to the needs identified in the baseline assessment. A follow-up assessment was conducted directly after the training. Effectiveness of the intervention was assessed via uncontrolled before-and-after comparison.

Results: Baseline knowledge score (13.0/25) showed a significant increase to 19.0/25 in follow-up. Baseline-Compliance was 23.7% and increased significantly to 71.5% in follow-up. Compliance rose significantly across all professional groups except for midwifes and in all indications for HH, with the largest in the indication “Before aseptic tasks”. The increase in compliance was associated with the intervention and remained significant after adjusting for confounders. The local pharmacy successfully supplies the entire hospital. The local supply resulted in a ten-fold increase of monthly hospital disinfectant consumption.

Conclusion: The WHO HH strategy is an adaptable and effective method to improve HH knowledge and compliance in a resource-limited setting. Local production is a feasible method for providing self-sufficient supply of ABHR to regional hospitals like the FRH. Participatory approaches like hygiene committee ownership builds confidence of sustainability.
Environmental factors and spatiotemporal distribution of Japanese encephalitis after vaccination campaign in Guizhou Province, China (2004–2016)
Authors: Zhao Suye , Li Yidan , Fu Shihong , Liu Ming , Li Fan , Liu Chunting , Yu Jing , Rui Liping , Wang Dingming , Wang Huanyu , Tian Huaiyu
Published: February 2020

Background Although a vaccination campaign has been conducted since 2004, Japanese encephalitis (JE) is still a public health problem in Guizhou, one of the provinces with the highest incidence of JE in China. The aim of this study was to understand the spatiotemporal distribution of JE and its relationship with environmental factors in Guizhou Province in the post-vaccination era, 2004–2016. Methods We collected data on human JE cases in Guizhou Province from 2004 to 2016 from the national infectious disease reporting system. A Poisson regression model was used to analyze the relationship between JE occurrence and environmental factors amongst counties. Results Our results showed that the incidence and mortality of JE decreased after the initiation of vaccination. JE cases were mainly concentrated in preschool and school-age children and the number of cases in children over age 15 years was significantly decreased compared with the previous 10 years; the seasonality of JE before and after the use of vaccines was unchanged. JE incidence was positively associated with cultivated land and negatively associated with gross domestic product (GDP) per capita, vegetation coverage, and developed land. In areas with cultivated land coverage <25%, vegetation coverage >55%, and urban area coverage >25%, the JE risk was lower. The highest JE incidence was among mid-level GDP per capita areas and in moderately urbanized areas. Conclusions This study assessed the relationship between incidence of JE and environmental factors in Guizhou Province. Our results highlight that the highest risk of JE transmission in the post-vaccination era is in mid-level developed areas. Keywords: Japanese encephalitis; spatial analysis; spatial epidemiology;mosquito; vaccine
Can direct smear results that are routinely collected at health centre level be used for monitoring the impact of mass drug administration with praziquantel on schistosomiasis in Burundi? A preliminary assessment.
Authors: BIZIMANA Paul , POLMAN Katja , ORTU Giuseppina , KRIT Meryam , NSABIYUMVA Frédéric , NKESHIMANA Audace , BIJABUKA Urlich , NIBAKIRE Marcelline , GEERTRUYDEN Jean-Pierre VAN
Published: February 2020

Background : Intestinal schistosomiasis is still a public health problem in Burundi. Since 2008, annual mass drug administration with praziquantel have been rolled out in 11 endemic districts. The national programme relies on school-based surveys with Kato-Katz to monitor the impact of mass drug administration. We explored whether routine data on intestinal schistosomiasis as determined by direct fecal smears at health centre level could be used.

Methods : From the Burundian National Health Information System, we collected routine incidence data on intestinal schistosomiasis as determined by direct smear examination in all 45 sanitary districts between 2011 and 2015. A temporal trends analysis was performed using a mixed negative binomial regression. Sanitary districts with mass drug administration campaigns with praziquantel (n=11) were compared with those without (n=34). In addition, prevalence data on intestinal schistosomiasis based on Kato-Katz results from a school-based national mapping in 2014 were compared with the incidence data in health centres based on direct smear results, in the same 45 sanitary districts.

Findings : In the 11 sanitary districts applying mass drug administration with praziquantel, the incidence rate decreased significantly for the years 2014 (β 2014 =-0.826, p=0.010) and 2015 (β 2015 =-1.294, p<0.001) and for the five-year period (β=-0.286, p<0.001), whereas in the 34 districts where mass drug administration was not delivered, there was no significant decrease over time (β=-0.087, p=0.219). In most of the 45 sanitary districts, the low prevalences based on Kato-Katz in schoolchildren were confirmed by low incidence rates based on direct smear in the health centres.

Conclusions : National Health Information System surveillance data, based on routinely collected direct smear results at health centre level, may be able to monitor the impact of mass drug administration with praziquantel on intestinal schistosomiasis in Burundi. Control and elimination of intestinal schistosomiasis call for integration of adequate diagnosis and treatment into routine activities of primary health care facilities, as recommended by the World Health Organization since more than 20 years. When moving towards elimination, more sensitive tests, such as the Point-of-care Circulating Cathodic Antigen assay are desirable.

Keywords : Direct smear, Health centre, Mass drug administration, Monitoring, Praziquantel, Routine data, Schistosomiasis, Burundi
Genome-wide identification and characterization of lectin receptor-like kinase gene family in cucumber and expression profiling analysis under different treatments
Authors: Lv Duo , Wang Gang , Xiong Liang-Rong , Sun Jing-Xian , Chen Yue , Guo Chun-Li , Yu Yao , He Huan-Le , Cai Run , Pan Junsong
Published: February 2020

Background: Lectin receptor-like kinases (LecRLKs) are a class of membrane proteins found in plants that are involved in diverse functions, including plant development and stress responses. Although LecRLK families have been identified in a variety of plants, a comprehensive analysis has not yet been undertaken in cucumber (Cucumis sativus L.). Results: In this study, 46 putative LecRLK genes were identified in cucumber genome, including 23 G-type, 22 L-type and 1 C-type LecRLK genes. They unequally distributed on all 7 chromosomes with a clustering trendency. Most of the genes in the cucumber LecRLK (CsLecRLK) gene family lacked introns. In addition, there were many regulatory elements associated with phytohormone and stress on these genes’ promoters. Transcriptome data demonstrated that distinct expression patterns of CsLecRLK genes in various tissues. Furthermore, we found that each member of the CsLecRLK family had its own unique expression pattern under hormone and stress treatment by the quantitative real time PCR (qRT-PCR) analysis.Conclusion: This study provides a better understanding of the evolution and function of LecRLK gene family in cucumber, and opens the possibility to explore the roles that LecRLKs might play in the life cycle of cucumber.
In vitro and Numerical Simulation of Blood Removal from Cerebrospinal Fluid: Comparison of Lumbar Drain to Neurapheresis Therapy
Authors: Khani Mohammadreza , Sass Lucas , Sharp M. Keith , McCabe Aaron , Verbick Laura Zitella , Lad Shivanand , martin bryn
Published: February 2020

Background: Blood removal from cerebrospinal fluid (CSF) in post-subarachnoid hemorrhage patients may reduce the risk of related secondary brain injury. We formulated a computational fluid dynamics (CFD) model to investigate the impact of a dual-lumen catheter-based CSF filtration system, called Neurapheresis TM therapy, on blood removal from CSF compared to lumbar drain.
Methods: A subject-specific multiphase CFD model of CSF system-wide solute transport was constructed based on MRI measurements. The Neurapheresis catheter geometry was added to the model within the spinal subarachnoid space. Neurapheresis flow aspiration and return rate was 2.0 and 1.8 (mL/min), versus 0.2 (mL/min) drainage for lumbar drain. Blood was modeled as a bulk fluid phase within CSF with a 10% initial tracer concentration and identical viscosity and density as CSF. Subject-specific oscillatory CSF flow was applied at the model inlet. The dura and spinal cord geometry were considered to be stationary. Spatial-temporal tracer concentration was quantified based on time-average steady-streaming velocities throughout the domain under Neurapheresis therapy and lumbar drain. To help verify CFD results, an optically clear in vitro CSF model was constructed with fluorescein used as a blood surrogate. Quantitative comparison of numerical and in vitro results was performed by linear regression of spatial-temporal tracer concentration over 24-hours.
Results: After 24-hours, tracer concentration was reduced to 4.9% under Neurapheresis therapy compared to 6.5% under lumbar drain. Tracer clearance was most rapid between the catheter aspiration and return ports. Neurapheresis therapy was found to have a greater impact on steady-streaming compared to lumbar drain. Steady-streaming in the cranial SAS was ~50X smaller than in the spinal subarachnoid space for both cases. CFD results were strongly correlated with the in vitro spatial-temporal tracer concentration under Neurapheresis therapy (R 2 =0.89 with +2.13% and -1.93% tracer concentration confidence interval).
Conclusion: A subject-specific CFD model of CSF system-wide solute transport was used to investigate the impact of Neurapheresis therapy on tracer removal from CSF compared to lumbar drain over a 24-hour period. Neurapheresis therapy was found to substantially increase tracer clearance compared to lumbar drain. The multiphase CFD results were verified by in vitro fluorescein tracer experiments.
Early open reduction of dislocated hips using a modified Smith-Petersen approach in arthrogyposis multiplex congenita
Authors: Miao Mingyuan , Cai Haiqing , Wang Zhigang , Hu Liwei , Bian Jingxia , Cai Haoqi
Published: February 2020

Background: Arthrogryposis multiplex congenita (AMC) is a rare syndrome with multiple joint contractures. Within the medical community, there is controversy surrounding AMC in terms of the ideal surgical approach and age for performing a reduction of dislocated hips. The purpose of this retrospective study was to evaluate the clinical outcomes of early open reduction of infant hip dislocation with arthrogryposis multiplex congenita following a modified Smith-Petersen approach that preserves the rectus femoris.
Methods: From 2010 to 2017, we performed this procedure on 28 dislocated hips in 20 infants under 12 months of age with AMC. The clinical and radiology data were reviewed retrospectively. The mean age at surgery was 6.9 ± 5.1 months, with a mean follow-up of 42.4 ± 41.1 months.
Results: After open reduction, the average hip acetabular index (AI), the international hip dysplasia institute classification (IHDI), and the hip range of motion significantly improved (all P<0.001). After the surgery, 16 patients were community walkers, and four patients were home walkers. Three hips in two patients required secondary revision surgery for residual acetabular dysplasia with combined pelvic osteotomy and femoral osteotomy. Seven of the hips that had been operated on showed signs of avascular necrosis (AVN). Among them, four were degree II, two were degree III, and one was degree IV. Multiple linear regression analysis demonstrated that greater age (in months) heightened the risk for secondary revision surgery (P=0.032).
Conclusions: The modified Smith-Petersen approach preserving the rectus femoris is an encouraging and safe option for treating hip dislocation in young AMC patients (before 12 months). If surgery takes place at less than 12 months of age for patients with AMC, this earlier open reduction for hip dislocation may reduce the chances of secondary revision surgery.
Mode of delivery and weight shape the intestinal microbiome composition progression in preterm infants: results of a prospective study
Authors: Heida Fardou , Kooi Elisabeth , Nguyen Thi-Yen , Hulscher Jan , Zoonen Anne van , Bos Arend , Harmsen Hermie , Goffau Marcus de
Published: February 2020

Background: In preterm infants the intestinal microbiome differs markedly from term infants. However, it is unclear whether the microbiome follows infant specific maturation patterns or whether it is mainly characterized by varying states of dysbiosis. We investigated the development of the intestinal microbiome in extremely preterm infants over time by 16S rRNA amplicon sequencing. We analysed the first meconium and faecal samples from the 2 nd , 3 rd and 4 th weeks, and (clinical) metadata to identify the main factors influencing the microbiota composition development. Results: The study included 41 extremely preterm infants (gestational age 25-30 weeks; birth weight (BW) 430-990g). Birth via Caesarean section (CS) was associated with placental insufficiency during pregnancy and lower BW. In meconium and in weeks 2 and 3 an increased combined abundance of Escherichia and Bacteroides (maternal aerotolerant fecal bacteria) was associated with vaginal delivery (p=0.039, p=0.0002, p=0.034, respectively) while Staphylococcus epidermidis (skin bacterium) was associated with CS (p=0.001, p=0.0003 p=0.048, respectively). Secondly, a switch was observed from a microbiome dominated by S. epidermidis (Bacilli) towards a microbiome dominated by Enterobacteriaceae (Gammaproteobacteria, mainly represented by Klebsiella and Escherichia ), in which the stage of progression appeared to be dependent upon the current weight of the infant, irrespective of the week of sampling or the mode of birth. Conclusions: Our data shows that the mode of delivery does affect the meconium microbiome composition. It also suggests that the weight of the infant at the time of sampling is a better predictor for the stage of progression of the intestinal microbiome development/maturation than gestational/postnatal age. We hypothesize that impaired growth, for example due the effects of diminished placental function during pregnancy, is a key factor in the maturation of the intestinal microbiome in extreme premature infants.
Development and validation of a CT-TA nomogram for preoperatively differentiating thymic epithelial tumor histologic subtypes
Authors: Ren Caiyue , Li Mingli , Zhang Yunyan , Zhang Shengjian
Published: February 2020

Background: Thymic epithelial tumors (TETs) are the most common primary tumors in the anterior mediastinum with considerable histologic heterogeneity. This study aimed to develop and validate a nomogram based on computed tomography (CT) and texture analysis (TA) for preoperatively predicting pathological classification for TET patients.Methods: Totally 172 patients with pathologically confirmed TET after surgery were retrospectively analyzed and randomly divided into a training cohort (n=120) and a validation cohort (n=52). Preoperative clinical demographic, CT signs and texture features of each patient were analyzed and prediction models were developed using the least absolute shrinkage and selection operator (LASSO) regression. The performance of models was evaluated and compared by the area under receiver operating characteristic (ROC) curve (AUC) and DeLong test. The clinical application value of models was determined through the decision curve analysis (DCA). Then a nomogram was developed based on the model with the best predictive accuracy and clinical utility and validated using the calibration plots.Results: Totally 87 patients with low-risk TET (LTET) (types A, AB, B1) and 85 patients with high-risk TET (HTET) (types B2, B3, C) were enrolled in this study. We separately constructed 4 prediction models for differentiating LTET from HTET using clinical, CT, texture features and their combination. These 4 prediction models achieved AUC values of 0.66, 0.79, 0.82, 0.88 in the training cohort and 0.64, 0.82, 0.86, 0.94 in the validation cohort, respectively. DeLong test and DCA analysis showed that the Combined model consisting of 2 CT signs and 2 texture parameters held the highest predictive efficiency and clinical utility ( p <0.05). A prediction nomogram was subsequently developed using the combined model’s 4 independently risk factors. The calibration curves indicated a good consistency between the actual observation and nomogram prediction for differentiating TET classifications.Conclusion: A prediction nomogram incorporating both the CT and texture parameters was constructed and validated in our study, which was conveniently used to facilitate the preoperative individualized prediction of simplified histologic subtypes in TET patients, assisting in clinical treatment decision making and achieving precision treatment.
Fatty acid synthase (FASN), a novel signature for visceral adipose tissues, regulates proliferation, migration and predicts prognosis of clear cell renal cell carcinoma
Authors: Xu Wen-Hao , Anwaier Aihetaimujiang , Wang Hong-Kai , Wang Jun , Zhu Wen-Kai , Tian Xi , Ma Chung-Guang , Wan Fang-Ning , Cao Da-Long , Shi Guo-Hai , Qu Yuan-Yuan , Zhang Hai-Liang , Ye Ding-Wei
Published: February 2020

Background: Growing evidence has indicated obesity one of the important etiological indicators of clear cell renal cell carcinoma (ccRCC). This study aims to investigated FASN mRNA expression in anthropometric adipose tissue, and elucidate prognostic value and potential functions in ccRCC patients. Methods: Transcriptional expression profiles was obtained from 380 paired ccRCC and adjacent normal tissues from Fudan University Shanghai Cancer Center (FUSCC) and 533 ccRCC samples from the Cancer Genome Atlas (TCGA) cohort. The visceral adipose tissue (VAT) and the subcutaneous adipose tissue (SAT) at the level of the umbilicus were measured using magnetic resonance imaging. The Kaplan-Meier method and log-rank test, with cooperation from Cox regression analysis, were used in survival analysis. Subsequently, we transiently transfected FASN plasmid into A498 and 786O cells, and investigated the role of FASN in ccRCC cell proliferation, apoptosis and migration in vitro. Related hub gens, functional annotations and significant signal pathways were predicted using integrated bioinformatics. Results: FASN mRNA expression was significantly higher in tumor than normal tissues in 913 ccRCC patients from FUSCC and TCGA cohorts. In addition, increased FASN mRNA expression was significantly relevant to advanced T stage ( p <0.001), N stage ( p =0.019), and AJCC stage ( p =0.002). Pearson’s correlation coefficient indicated that FASN amplification positively correlated with VAT% ( r =0.772, p <0.001). VAT% was significantly correlated with poor PFS and OS, with hazard ratios of 2.066 (1.113-7.261, p =0.028) and 2.773 (1.168-8.974, p =0.023) in FUSCC. Meanwhile, ccRCC patients with elevated FASN expression significantly responded for poor PFS and OS, with hazard ratios of 1.529 (1.135-2.061, p =0.005) and 1.450 (1.030-2.041, p =0.033). Next, after transfection efficiency was verified in A498 and 786O cells, we found transient inhibition and overexpression of FASN significantly regulates cells proliferation and migration abilities, and inhibition of FASN displayed higher apoptotic rate in ccRCC cells. Conclusion: In conclusion, this study demonstrated that FASN mRNA expression is positively related with aggressive proliferation, migration progression and predicts prognosis of ccRCC. In addition, we first reveal that elevated FASN mRNA expression is significantly correlated with abdominal obesity distribution, especially VAT%, which also is a significant predictor of poor prognosis in patients with ccRCC.
A panel of DNA methylation signature from peripheral blood may predict colorectal cancer susceptibility
Authors: Onwuka Justina Ucheojor , Li Dapeng , Liu Yupeng , Huang Hao , Xu Jing , Liu Ying , Zhao Yashuang , Zhang Yuanyuan
Published: February 2020

Background Differential DNA methylation panel derived from peripheral blood could serve as biomarkers of CRC susceptibility. However, most of the previous studies utilized post-diagnostic blood DNA which may be markers of disease rather than susceptibility. In addition, to date no study has evaluated the predictive potential of such markers in a prospective cohort and on a genome-wide basis. The aim of this study was to identify potential panel of DNA methylation biomarkers in peripheral blood that are associated with CRC risk and therefore serve as epigenetic biomarkers of disease susceptibility. Methods DNA methylation profile of a nested case-control study with 166 CRC and 424 healthy normal subjects were obtained from Gene Expression Omnibus (GEO) database. The differentially methylated markers were identified by moderated t-statistics. The DNA methylation panel were constructed by stepwise logistic regression and least absolute shrinkage and selection operator in training dataset. A methylation risk score (MRS) model was constructed and the association between MRS and CRC risk assessed. Results We identified 48 differentially methylated CpGs sites, of which 33 were hypomethylated. Of these, sixteen-CpG based MRS that was associated with CRC risk (OR = 2.68, 95% CI: 2.13, 3.38, P < 0.0001) was constructed. This association is confirmed in the testing dataset (OR = 2.02, 95% CI: 1.48, 2.74, P < 0.0001) and persisted in both males and females, younger and older subjects, short and long time-to-diagnosis. The MRS also predicted CRC with AUC 0.82 (95% CI: 0.76, 0.88), indicating high accuracy. Conclusions Our study has identified a novel DNA methylation panel that is associated with CRC and could be-useful for the prediction of CRC risk in the future.
Farnesal-loaded pH-sensitive polymeric micelles provided effective prevention and treatment on dental caries
Authors: Yi Youping , Wang Lujun , Chen Lin , Lin Yan , Luo Zhongling , Chen Zhenyu , Li Ting , Wu Jianming , Zhong Zhirong
Published: February 2020

Background: Farnesol is a sesquiterpene from propolis and citrus fruit that shows promising anti-bacterial activity for caries treatment and prevention, but its hydrophobicity limits the clinical application. We aimed to develop the novel polymeric micelles (PMs) containing a kind of derivative of farnesol and a ligand of pyrophosphate (PPi) that mediated PMs to adhere tightly with the tooth enamel.Results: Farnesal (Far) was derived from farnesol and successfully linked to PEG via an acid-labile hydrazone bond to form PEG-hyd-Far, which was then conjugated to PPi and loaded into PMs to form the aimed novel drug delivery system, PPi-Far-PMs. The in vitro test about the binding of PPi-Far-PMs to hydroxyapatite showed that PPi-Far-PMs could bind rapidly to hydroxyapatite and quickly release Far under the acidic conditions. Results from the mechanical testing and the micro-computed tomography indicated that PPi-Far-PMs could restore the microarchitecture of teeth with caries. Moreover, PPi-Far-PMs diminished the incidence and severity of smooth and sulcal surface caries in rats that were infected with Streptococcus mutans while being fed with a high-sucrose diet . The anti-caries efficacy of free Far can be improved significantly by PPi-Far-PMs through the effective binding of it with tooth enamel via PPi.Conclusions: This novel drug-delivery system may be useful for the treatment and prevention of dental caries as well as the targeting therapy of anti-bacterial drugs in the oral disease.
Ovarian inguinal hernia – a possibility in MURCS syndrome
Authors: Saini Rahul , Bains Lovenish , Kaur Tarangpreet , Lal Pawan , Pal Veer , Beg Mohd Yasir , Kaur Daljit
Published: February 2020

Background Inguinal hernia containing ovary can be found in paediatric population and is a rare finding in women of reproductive age group. Most of the cases are associated with congenital abnormalities of the female genital tract. Case Presentation A 20 year old female presented with right reducible inguinal hernia, primary amenorrhea and normal secondary sexual characteristics. Clinical examination revealed scoliosis with convexity towards left side, prominence of left rib cage with sprengel deformity and right sided heart sounds. Ultrasound of the inguinal swelling revealed right ovary within the hernial sac, Chest X-ray revealed right lung collapse and dextrocardia. Further Magnetic resonance imaging (MRI) of pelvis revealed inguinal hernia with right ovary as its content, normal left ovary and absent uterus. Computed tomography (CT) revealed complete collapse of right lung with compensatory left lung hyperinflation and absent right kidney. Karyotyping of the patient was normal, 46XX. A diagnosis of MURCS syndrome with right ovarian hernia was made. The hernia was surgically managed with repositioning of ovary into the pelvis. Discussion Ovary in inguinal hernia is rare in women of reproductive age group. MRKH syndrome, a mullerian duct anomaly, is the congenital aplasia of uterus and upper two-thirds of vagina in a female with normal ovaries, fallopian tube, secondary sexual characteristics and 46XX karyotype. MURCS is a subtype of MRKH type 2 having mullerian duct agenesis with renal, cardiac, muscular & vertebral defects. General physical examination and primary investigations if yields abnormal findings; the patient must undergo an array of investigations to rule out MRKH/MURCS, or other congenital abnormality. Early diagnosis is essential to prevent its incarceration or torsion. The primary treatment of ovary in inguinal hernia is repositioning the ovary back to pelvis to preserve fertility and repair of inguinal hernia. A multidisciplinary team is required to deal with various abnormalities present in a patient with MURCS.
Evaluation of injection-site-related adverse events with galcanezumab: a post hoc analysis of Phase 3 studies in participants with migraine
Authors: Stauffer Virginia , Wang Shufang , Bonner Jo , Kim ByungKun , Bhandari Rohit , Day Kathleen A. , Camporeale Angelo
Published: February 2020

Background: Injection-site reactions have been reported with biologicals. In this post hoc analysis of Phase 3 studies in participants with migraine, we provide a comprehensive overview and detailed summary of injection-site reaction with galcanezumab.Methods: Data were obtained from two randomised clinical studies in participants with episodic migraine (EVOLVE-1 and EVOLVE-2), one randomised study in participants with chronic migraine (REGAIN) and one open-label study (Study CGAJ) in participants with episodic or chronic migraine. The injection-site reactions were measured for two different cohorts: 1) six-month double-blind treatment phase in the EVOLVE-1 and EVOLVE-2 studies and three-month double-blind treatment phase in the REGAIN study, where participants received placebo and galcanezumab (placebo-controlled analysis set); 2) three month double-blind (Month 0 to Month 3; 1:1:placebo:galcanezumab) + nine months open-label extension phase (Month 3 to Month 12) of REGAIN and twelve month open-label phase of Study CGAJ, where participants received only galcanezumab (galcanezumab exposure analysis set).Results: A total of 477 participants in the placebo-controlled analysis set (galcanezumab 240 mg, 166/730 [22.7%]; galcanezumab 120 mg, 128/705 [18.2%]; placebo, 183/1451 [12.6%]) reported at least one injection-site reaction. Most of the injection-site reactions were reported as injection-site pain, unspecified injection-site reaction, injection-site erythema, and injection-site pruritus. The incidence of injection-site pain was highest among all reported Injection-site reactions and were reported with similar frequency by participants receiving galcanezumab (galcanezumab 120mg, 10.1%; galcanezumab 240 mg, 11.6%) and placebo (9.5%) and was the most common injection-site reaction reported within 60 minutes of injection (~86% of participants). The frequency of unspecified injection-site reaction, injection-site erythema and injection-site pruritus was significantly (P<0.001) higher in participant receiving galcanezumab versus placebo. In the galcanezumab exposure analysis set participants received up to 12 doses and the frequency of injection-site reactions reported for both doses combined was 21.8%. The reporting of injection-site reactions did not increase with the number of doses received. No ISR-related serious adverse events were reported in both the placebo-controlled and galcanezumab exposure analysis sets.Conclusions: The most common adverse event of galcanezumab is injection-site reactions. However, these events were generally mild-to-moderate in severity, non-serious, resolved spontaneously, and discontinuations due to injection-site reactions were low (1%).Trial registration: Clinicaltrials.gov identifier: NCT02614183, NCT02614196, NCT02614261, NCT02614287.