bluuebunny/crossref_metadata_2025 huggingface dataset:
Problematic Internet Use in Children and Adolescents: Associations with psychiatric disorders and impairment
Authors: Restrepo Anita , Scheininger Tohar , Clucas Jon , Alexander Lindsay , Salum Giovanni , Georgiades Kathy , Paksarian Diana , Merikangas Kathleen , Milham Michael
Published: February 2020

Background: Problematic internet use (PIU) is an increasingly worrisome issue, as youth population studies are establishing links with internalizing and externalizing problems. There is a need for a better understanding of psychiatric diagnostic profiles associated with this issue, as well as its unique contributions to impairment. Here, we leveraged the ongoing, large-scale Child Mind Institute Healthy Brain Network, a transdiagnostic self-referred, community sample of children and adolescents (ages 5-21), to examine the associations between PIU and psychopathology, general impairment, physical health and sleep disturbances.
Methods: A total sample of 564 (190 female) participants between the ages of 7-15 (mean = 10.80, SD = 2.16), along with their parents/guardians, completed diagnostic interviews with clinicians, answered a wide range of self-report (SR) and parent-report (PR) questionnaires, including the Internet Addiction Test (IAT) and underwent physical testing as part of the Healthy Brain Network protocol.
Results: PIU was positively associated with depressive disorders (SR: aOR = 2.43, CI: 1.22-4.74, p = .01; PR: aOR = 2.56, CI: 1.31-5.05, p = .01), the combined presentation of ADHD (SR: aOR = 1.91, CI: 1.14-3.22, p = .01; PR: n.s.), Autism Spectrum Disorder (SR: n.s.; PR: aOR = 2.24, CI: 1.34-3.73, p < .001), greater levels of impairment (SR: Standardized Beta = 4.63, CI: 3.06-6.20, p < .001; PR: Standardized Beta = 5.05, CI: 3.67-6.42, p < .001) and increased sleep disturbances (SR: Standardized Beta = 3.15, CI: 0.71-5.59, p = .01; PR: Standardized Beta = 3.55, CI: 1.34-5.75, p < .001), even when accounting for demographic covariates and psychiatric comorbidity.
Conclusions: The association between PIU and psychopathology, as well as its impact on impairment and sleep disturbances, highlight the urgent need to gain an understanding of mechanisms in order to inform public health recommendations on internet use in U.S. youth.
Expert Curation of the Human and Mouse Olfactory Receptor Gene Repertoires Identifies Conserved Coding Regions Split Across Two Exons.
Authors: Barnes If Habib Ahmed , Ibarra-Soria Ximena , Fitzgerald Stephen , Gonzalez Jose Manuel , Davidson Claire , Hardy Matthew Philip , Manthravadi Deepa , Gerven Laura Van , Jorissen Mark , Zeng Zhen , Khan Mona , Mombaerts Peter , Harrow Jennifer , Logan Darren William , Frankish Adam
Published: February 2020

Background Olfactory receptor (OR) genes are the largest multi-gene family in the mammalian genome, with 874 in human and 1483 loci in mouse (including pseudogenes). The expansion of the OR gene repertoire has occurred through numerous duplication events followed by diversification, resulting in a large number of highly similar paralogous genes. These characteristics have made the annotation of the complete OR gene repertoire a complex task. Most OR genes have been predicted in silico and are typically annotated as intronless coding sequences. Results Here we have developed an expert curation pipeline to analyse and annotate every OR gene in the human and mouse reference genomes. By combining evidence from structural features, evolutionary conservation and experimental data, we have unified the annotation of these gene families, and have systematically determined the protein-coding potential of each locus. We have defined the non-coding regions of many OR genes, enabling us to generate full-length transcript models. We found that 13 human and 41 mouse OR loci have coding sequences that are split across two exons. These split OR genes are conserved across mammals, and are expressed at the same level as protein-coding OR genes with an intronless coding region. Our findings challenge the long-standing and widespread notion that the coding region of a vertebrate OR gene is contained within a single exon. Conclusions This work provides the most comprehensive curation effort of the human and mouse OR gene repertoires to date. The complete annotation has been integrated into the GENCODE reference gene set, for immediate availability to the research community.
Does the medical insurance system really achieved the effect of poverty alleviation for the middle-aged and elderly people in China?Characteristics of vulnerable groups and failure links.
Authors: Ma Meiyan , Li Ye , Wang Nianshi , Wu Qunhong , Shan Linghan , Jiao Mingli , Fu Xuelian , Li Heng , Sun Tao , Yi Bin , Tian Wanxin , Xia Qi , Shi Baoguo , Hao Yanhua , Yin Hui , Ning Ning , Gao Lijun , Liang Libo , Wang Jiahui
Published: February 2020

Objective ： We examined the physiological, household, and spatial agglomeration characteristics of the health poverty population in China. We identified weak links that affect the implementation of the medical insurance and further improve its effectiveness for health poverty alleviation. Methods: A national representative sample from the 2015 China Health and Pension Tracking Survey (CHARLS) was analyzed. The WHO recommended method was adopted to calculate catastrophic health expenditure (CHE) and impoverishment by medical expenses (IME). We created a binary indicator for IME as the outcome variable and applied the treatment-effect model to analyze the determinants of IME. Results ： The rate of IME was 7.2% of the overall population, compared to 20.3% of the sample households trapped in CHE. The rate of IME enrolled in insurance schemes was 7.4% higher than that of uninsured families (4.8%). Economic level, living area, family size, age of household head, having hospitalized members, and participating in insurance were statistically significant for the rate of IME. Conclusion ： The original poverty -promoting policies has not reached the maximum point of convergence with China’s current demand for health. The overlapped health vulnerabilities exacerbated the risk of poverty among the elderly and households with high health needs and utilization. In addition, the medical insurance schemes have proven to be insufficient for protection against economic burden of poor households. So, special health needs, age, and household capacity to pay should be comprehensively considered while strengthening the connection between the disease insurance scheme with supplementary insurance. Keywords: medical insurance, poverty alleviation, healthy poverty, catastrophic health expenditure, impoverishment by medical expenses.
Rapid shifts in the age-specific burden of malaria following successful control interventions in four regions of Uganda
Authors: Kigozi Simon P. , Kigozi Ruth N. , Epstein Adrienne , Mpimbaza Arthur , Sserwanga Asadu , Yeka Adoke , Nankabirwa Joaniter I. , Halliday Katherine , Pullan Rachel L , Rutazaana Damian , Sebuguzi Catherine M , Opigo Jimmy , Kamya Moses R , Staedke Sarah G , Dorsey Grant , Greenhouse Bryan , Rodriguez-Barraquer Isabel
Published: February 2020

Background: Malaria control using long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) has been associated with reduced transmission throughout Africa. However, the impact of transmission reduction on the age distribution of malaria cases remains unclear.
Methods: Over a 10-year period (January, 2009 to July, 2018), outpatient surveillance data from four health facilities in Uganda were used to estimate the impact of control interventions on temporal changes in the age distribution of malaria cases using multinomial regression. Interventions included mass distribution of LLINs at all sites and IRS at two sites.
Results: Overall, 896,550 patient visits were included in the study; 211,632 aged <5 years, 171,166 aged 5-15 years, and 513,752 >15 years. Over time, the age distribution of patients not suspected of malaria and those malaria negative either declined or remained the same across all sites. In contrast, the age distribution of suspected and confirmed malaria cases increased across all four sites. In the two LLINs-only sites, the proportion of malaria cases in <5 years decreased from 31% to 16% and 35% to 25%, respectively. In the two sites receiving LLINs plus IRS, these proportions decreased from 58% to 30% and 64% to 47%, respectively. Similarly, in the LLINs-only sites, the proportion of malaria cases >15 years increased from 40% to 61% and 29% to 39%, respectively. In the sites receiving LLINs plus IRS, these proportions increased from 19% to 44% and 18% to 31%, respectively.
Discussion: These findings demonstrate a shift in the burden of malaria from younger to older individuals following implementation of successful control interventions, which has important implications for malaria prevention, surveillance, case management and control strategies.
Prdx1 Promotes the Loss of Primary Cilia in Esophageal Squamous Cell Carcinoma
Authors: Chen Qiongzhen , Li Jinmeng , Yang Xiaoning , Ma Junfeng , Gong Fanghua , Liu Yu
Published: February 2020

Background: Loss of primary cilia is frequently observed in tumor cells, suggesting that the absence of this organelle may promote tumorigenesis through aberrant signal transduction, the inability to exit the cell cycle, and promotion of tumor cell invasion. Primary cilia loss also occurs in esophageal squamous cell carcinoma (ESCC) cells, but the molecular mechanisms that explain how ESCC cells lose primary cilia remain poorly understood.

Methods: Inhibiting the expression of Prdx1 in the ESCC cells to detect the up-regulated genes related to cilium regeneration and down-regulated genes related to cilium disassembly by Gene chip. And, mice and cell experiments were carried to confirm the role of the HEF1-Aurora A-HDAC6 signaling axis in ESCC.

Results: In this study, we found that silencing Peroxiredoxin 1 (Prdx1) restores primary cilia formation, and over-expressing Prdx1 induces primary cilia loss in ESCC cells. We also showed that the expression of Prdx1 regulates the action of the HEF1-Aurora A-HDAC6 signaling axis to promote the disassembly of primary cilia, and suppression of Prdx1 results in decreased tumor formation and tumor mass volume in vivo.

Conclusions: These results suggest that Prdx1 is a novel regulator of primary cilia formation in ESCC cells.
Cholecystectomy outcomes after endoscopic sphincterotomy in patients with choledocholithiasis: A meta-analysis
Authors: Xu Jie , Yang Chuang
Published: February 2020

Background Endoscopic sphincterotomy is the standard treatment for common bile duct stones.There is different evidence considering complications specifically biliary pancreatitis and cholangitis with the use of cholecystectomy after endoscopic sphincterotomy.The purpose of this article is to compare the positive cholecystectomy after endoscopic treatment of common bile duct stones, whether the incidence of recurrent pancreatitis cholangitis is reduced, especially in high-risk patients. Methods We searched Pubmed(1990-2019)、Embase(1990-2019)和 Cochrane(1990-2019)database for trials comparing the 2 strategies for gallstones after ES.A related article on the removal of gallbladder after endoscopic sphincterotomy was collected,followed by analysis of each group using RevMan. Results We have adopted a total of 8 studies, including 7 randomized controlled trials and 1 retrospective study. A total of 12718 patients were included in the study, 4922 in the early cholecystectomy group, and 7795 in the gallbladder in situ group.During the follow-up period, 41 patients had pancreatitis after endoscopic sphincterotomy in the cholecystectomy group, and 177 patients in the wait-and-see group. The incidence of pancreatitis in the gallbladder in situ group was significantly reduced(RR 0.38, 95%CI 0.27 to 0.53, P < 0.00001,I 2 =0%).The incidence of cholangitis and jaundice in the removal of the gallbladder group was also less than that in the preserved gallbladder group(RR 0.31, 95%CI 0.26 to 0.38, P < 0.00001,I 2 =0%).There was no significant difference in mortality between the two groups(RR 0.73, 95%CI 0.52 to 1.02, P =0.07,I 2 =14%).There is a significant difference in cholecystitis or biliary colic(RR 0.25, 95% CI 0.21 to 0.29, P < 0.00001,I 2 =28%). Conclusions Early endoscopic cholecystectomy after removal of common bile duct stones can effectively reduce biliary complications such as recurrent pancreatitis, cholangitis and cholecystitis. This is still true for high-risk patients, and has no significant effect on the mortality of patients. After ES,laparoscopic cholecystectomy should be recommended.
Increased PD-1-positive macrophages in the tissue of gastric cancer are closely associated with poor prognosis in gastric cancer patients.
Authors: Kono Yusuke , Saito Hiroaki , Miyauchi Wataru , Shimizu Shota , Murakami Yuki , Shishido Yuji , Miyatani Kozo , Matsunaga Tomoyuki , Fukumoto Yoji , Nakayama Yuji , Sakurai Chiye , Hatsuzawa Kiyotaka , Fujiwara Yoshiyuki
Published: February 2020

Background: Programmed cell death 1 (PD-1) is one of the immune checkpoint molecules that negatively regulate the function of T cells. Although recent studies indicate that PD-1 is also expressed on other immune cells besides T cells, its role remains unclear. This study aims to evaluate PD-1 expression on macrophages and examine its effect on anti-tumor immunity in gastric cancer (GC) patients.
Methods : The frequency of PD-1 + macrophages obtained from GC tissue was determined by multicolor flow cytometry (n = 15). Double immunohistochemistry staining of PD-1 and CD68 was also performed to evaluate the correlations among the frequency of PD-1 + macrophages, clinicopathological characteristicus, and prognosis in GC patients (n = 102).
Results: The frequency of PD-1 + macrophages was significantly higher in GC tissue than in non-tumor gastric tissue. The phagocytotic activity of PD-1 + macrophages was severely impaired compared with that of PD-1 - macrophages. The 5-year disease specific survival rates in patients with PD-1 + macrophage Low (the frequency of PD-1 + macrophages; < 0.85%) and those with PD-1 + macrophage High (the frequency of PD-1 + macrophages; ≥ 0.85%) were 85.9% and 65.8%, respectively ( P = 0.008). Finally, multivariate analysis showed the frequency of PD-1 + macrophage to be an independent prognostic factor.
Conclusions: The function of PD-1 + macrophage was severely impaired and increased frequency of PD-1 + macrophage worsened the prognosis of GC patients. PD-1–PD-L1 therapies may function through a direct effect on macrophages in GC.
Antibiotic treatment regimens for bone infection after debridement ： a study of 902 cases
Authors: Wang Xiaohua , Fang Li , Wang Shulin , Chen Yueqi , Ma Huan , Zhao Hongwen , Xie Zhao
Published: February 2020

Purpose: Our aim was to investigate the clinical efficacy and complications of antibiotics treatment duration for the patients of bone infection.
Methods: We retrospectively analyzed the patients with bone infection admitted to our hospital between March 2013 and October 2018. The surgical debridement was performed and the patients were divided into three groups: IV group (Intravenous antibiotics for 2 weeks); Oral group (Intravenous antibiotics for 2 weeks followed by oral antibiotics for 4 weeks); Rifampicin group (Intravenous antibiotics for 2 weeks followed by oral antibiotics plus rifampicin for 4 weeks). The infection control rate and complications were compared.
Results ： A total of 902 patients were enrolled, the infection sites included 509 tibias, 228 femurs, 32 humeri, 23 radii and ulnae, 40 calcanei, 23 multiple-site infections and the other sites 47 cases. After at least 6 months of follow-up, 148 (16.4%) patients had recurrence of infection. The recurrence rate of IV group was 17.9%, which was no significant higher than that of Oral group (10.1%) or Rifampicin group (10.5%). The abnormal rate of Glutamic-pyruvic transaminase(ALT) in IV group was 15.1%, which was lower than that of Oral group (18.0%) and Rifampicin group (27.4%), P=0.026. The positive rates of proteinuria in the three groups were 3.2%, 4.5%, and 9.3%, respectively, P=0.020.
Conclusion: After debridement of bone infection, the additional oral antibiotic treatment may increase the damage of liver and kidney, and can not significantly reduce the infection recurrence rate. Therefore, it is recommended to adopt short-term systemic antibiotic treatment after debridement.
αβ-Dehydrocurvularin isolated from the fungus Aspergillus welwitschiae effectively inhibited the behaviour and development of the root-knot nematode Meloidogyne graminicola in rice roots
Authors: xiang Chao , Liu Ying , Liu Shi-Ming , Huang Ya-Fei , Kong Ling-An , Peng Huan , Liu Mao-Yan , Liu Jing , Peng De-Liang , Huang Wen-Kun
Published: February 2020

Background: The root-knot nematode Meloidogyne graminicola has become a serious threat to rice production as a result of the cultivation changes from transplanting to direct seeding. The nematicidal activity of Aspergillus welwitschiae have been investigated in vitro , and the disease control efficacy of the active compound has been evaluated under greenhouse and field conditions.
Results: The active compound αβ-dehydrocurvularin (αβ-DC), isolated by nematicidal assay-directed fractionation, showed significant nematicidal activity against M. graminicola , with an median lethal concentration (LC 50 ) value of 122.2 μg mL −1 . αβ-DC effectively decreased the attraction of rice roots to nematodes and the infection of nematodes and also suppressed the development of nematodes under greenhouse conditions. Moreover, αβ-DC efficiently reduced the root gall index under field conditions.
Conclusion: To our knowledge, this is the first report to describe the nematicidal activity of αβ-DC against M. graminicola . The results obtained under greenhouse and field conditions provide a basis for developing commercial formulations from αβ-DC to control M. graminicola in the future.
Keywords: Meloidogyne graminicola ; αβ-dehydrocurvularin; nematicidal activity; attractiveness; development; behaviour
Persistent postoperative pain and healthcare costs associated with instrumented and non-instrumented spinal surgery: a case-control study
Authors: Weir Sharada , Samnaliev Mihail , Kuo Tzu-Chun , Tierney Travis S. , Manca Andrea , Taylor Rod S. , Bruce Julie , Eldabe Sam , Cumming David
Published: February 2020

Purpose. To compare rates of persistent postoperative pain (PPP) after lumbar spine surgery—commonly known as Failed Back Surgery Syndrome—and healthcare costs for instrumented lumbar spinal fusion versus decompression/discectomy. Methods. UK population-based healthcare data from the Hospital Episode Statistics (HES) database from NHS Digital and the Clinical Practice Research Datalink (CPRD) were queried to identify patients with PPP following lumbar spinal surgery. Rates of PPP were calculated by type of surgery (instrumented and non-instrumented). Total healthcare costs associated with the surgery and covering the 24 month period after index hospital discharge were estimated using standard methods for classifying health care encounters into major categories of health care resource utilization (i.e., inpatient hospital stays, outpatient clinic visits, accident and emergency attendances, primary care encounters, and medications prescribed in primary care) and applying the appropriate unit costs (expressed in 2013 GBP). Results. Increasing the complexity of surgery with instrumentation was not associated with an increased rate of PPP. However, 2-year healthcare costs following discharge after surgery are significantly higher among patients who underwent instrumented surgery compared with decompression/discectomy. Conclusions. Although there is a not insubstantial risk of ongoing pain following spine surgery, with 1-in-5 patients experiencing PPP within two years of surgery, the choice of surgical procedure does not, by itself, appear to be a driving factor.
Reversible splenial lesion syndrome (RESLES) due to acute intermittent porphyria with a novel mutation in the hydroxymethylbilane synthase gene
Authors: li xiaoqing , han fei , chen qianlong , zhu tienan , zhao yongqiang , yu xuezhong , zhu huadong , cao jian , yang jing
Published: February 2020

Background: Reversible splenial lesion syndrome (RESLES) is a clinico-radiological syndrome characterized by the presence of reversible lesions specifically involving the splenium of the corpus callosum (SCC). The cause of RESLES is unknown. However, infectious-related mild encephalitis/encephalopathy (MERS) with a reversible splenial lesion remains the most common cause of reversible splenial lesions. Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a partial deficiency of porphobilinogen deaminase (PBGD), the third enzyme in the heme biosynthetic pathway. It can affect the autonomic, peripheral, and central nervous system. Result: In this study, we report a 20-year-old woman with AIP who presented with MRI manifestations suggestive of RESLES, she had a novel HMBS nonsense mutation, a G to A mutation in base 594, which changed tryptophan to a stop codon (W198*). Conclusion: To the best of our knowledge, this is only one published case of RELES associated with AIP.
Radiographic and clinical outcome of lumbar lateral interbody fusion for extreme lumbar spinal stenosis of Schizas grade D: a retrospective study
Authors: Li Jun , Li Hao , Ning Zhang , Wang Zhi-wei , Zhao Teng-fei , Chen Lin-wei , Chen Gang , Chen Qi-xin , Li Fang-cai
Published: February 2020

Background: Extreme lumbar spinal stenosis was thought to be a relative contraindication for lumbar lateral interbody fusion (LLIF) and was excluded in most studies. This is a retrospective study to analyze the radiographic and clinical outcome of LLIF for extreme lumbar spinal stenosis of Schizas grade D.Methods: For radiographic analysis, we included 202 segments from 124 patients who underwent LLIF between June 2017 and December 2018. Lumbar spinal stenosis was graded according to Schizas’ classification. Anterior and posterior disc heights, disc angle, foramen height, spinal canal diameter and central canal area were measured on CT and MRI. For clinical analysis, 18 patients with at least one segment of grade D were included. Visual analogue scale (VAS) and Oswestry disability index (ODI) scores were used to evaluate clinical outcome. Continuous variables were confronted by using Student's t-test, obtaining a statistically significant difference for values inferior to 0.05.Results: Among the 202 segments included for radiological evaluation, there were 42 grade A segments, 41 grade B segments, 101 grade C segments and 18 grade D segments. Postoperatively, the average change of midsagittal canal diameter of grade D was significantly greater than that of grade A, and not significantly different compared to grades B and C. As to the average changes of disc height, bilateral foraminal height, disc angle and central canal area (CCA), grade D was not significantly different from the others. The average postoperative CCA of grade D was significantly smaller than the average preoperative CCA of grade C. Eighteen patients with grade D stenosis were followed up for an average of 19.61 ± 6.32 months. Clinical evaluation revealed an average improvement in the ODI and VAS scores for back and leg pain by 20.77%, 3.67 and 4.15 points, respectively. Sixteen of 18 segments with grade D underwent posterior decompression.Conclusion: The radiographic decompression effect of LLIF for Schizas grade D segments were comparable with that of other grades. Posterior decompression was necessary for LLIF to achieve a satisfactory clinical outcome for extreme lumbar spinal stenosis of Schizas grade D.
Intracellular toxic advanced glycation end-products (TAGE) in myoblasts may cause sarcopenia: Research article of a non-clinical study
Authors: Takata Takanobu , Sakasai-Sakai Akiko , Takeuchi Masayoshi
Published: February 2020

Background: Sarcopenia is a progressive disease that is characterized by decreases in skeletal muscle mass and function. Skeletal muscle consists of myotubes that differentiated from myoblasts. Although sarcopenia is associated with non-alcoholic steatohepatitis (NASH) and type 2 diabetes mellitus (T2DM), the underlying mechanisms remain unclear. We considered that glyceraldehyde (GA), a glucose/fructose metabolism intermediate, plays a crucial role in sarcopenia. We previously designated GA-derived advanced glycation end-products (AGEs) as toxic AGEs (TAGE) because of their cytotoxicity and involvement in lifestyle-related diseases (LSRD), such as NASH and T2DM. We hypothesized that TAGE induce cytotoxicity in myoblasts.
Methods: C2C12 cells, which are murine myoblasts, were treated with 0, 0.5, 1, 1.5, and 2 mM GA for 24 h, and cell viability and intracellular TAGE were measured using WST-8 and slot blot assays. Cells were pretreated with 8 mM aminoguanidine (AG), an inhibitor of AGE production, for 2 h followed by 0, 1.5, and 2 mM GA for 24 h. Cell viability and intracellular TAGE were then measured. Serum TAGE levels in STAM mice, in which there were four stages (pre-simple steatosis, simple steatosis, steatohepatitis, and fibrosis), were measured using an enzyme-linked immunosorbent assay. Results were expressed as TAGE units (U) per milliliter of serum, with 1 U corresponding to 1.0 μg of GA-derived AGE-bovine serum albumin (BSA) (TAGE-BSA). The viabilities of cells treated with 20 μg/mL non-glycated BSA (NG-BSA) and TAGE-BSA for 24 h were assessed using the WST-8 assay.
Results: In C2C12 cells treated with 1.5 and 2 mM GA, cell viability decreased to 47.7 and 5.0% and intracellular TAGE increased to 6.0 and 15.9 μg/mg protein, respectively. Decreases in cell viability and TAGE production were completely inhibited by 8 mM AG. Serum TAGE levels at the steatohepatitis and fibrosis stages were 10.51 ±1.16 and 10.44±0.95 U/mL, respectively, and increased from the pre-simple steatosis stage. The viabilities of C2C12 cells treated with 20 μg/mL NG-BSA and TAGE-BSA were 99.7 and 88.3%, respectively.
Conclusion: Intracellular TAGE were generated in C2C12 cells and induced cell death more strongly than extracellular TAGE. Intracellular TAGE in myoblasts may cause sarcopenia in patients with LSRD.
Analysis of lifetime death probabilities for major death causes among residents in China
Authors: Yuan Ping , Xiang Jianjun , Chen Tiehui , Lin Xiuquan , Peng Xianer , Zheng Kuicheng
Published: February 2020

Background: Cumulative mortality rate and cumulative risk are the two commonly used indicators at present to measure the significance and severity of diseases, while both of them have limitations and cannot represent the life-time death probability. This study aims to use a new indicator, lifetime death probability (LDP), to estimate the lifetime death probabilities for the top five leading causes of death in China and explore the regional differences and trends over time. Methods: The LDPs were calculated using a probability additive formula and an abridged life table. Results: In 2014, the LDPs for heart disease, cerebrovascular disease, malignant tumor, respiratory disease, and injury and poisoning were 24.4%, 23.7%, 19.2%, 15.5%, and 5.3%, respectively. Compared to 2004-2005, the LDPs for heart disease and malignant tumor in 2014 increased 7.3% and 0.5%, respectively. In contrast, the LDPs for cerebrovascular and respiratory diseases in 2014 were 1.0% and 3.9% respectively lower than that in 2004-2005. In the eastern region, malignant tumors had the highest LDP among the five diseases, while in the central and western regions they were ‘cerebrovascular and heat diseases’ and ‘respiratory diseases, and injury and poisoning’, respectively. Conclusions: LDP is an effective indicator for comparing health outcomes, which can be applied in future disease surveillance. Heart disease and cancer are the two major lifetime risks of death in China, but with regional differences. There is a need to take targeted preventive measures to prevent diseases in different regions.
Intra-carotid arterial transfusion of circulatory-derived autologous CD34+ cells in rodent after ischemic stroke — evaluate the impact of therapeutic time points on prognostic outcomes
Authors: Lin Kun-Chen , Chai Han-Tan , Chen Kuan-Hung , Sung Pei‐Hsun , Chiang John Y. , Shao Pei-Lin , Huang Chi-Ruei , Li Yi-Chen , Ko Sheung-Fat , Yip Hon-Kan
Published: February 2020

Background This study tested the optimal time point for left intra-carotid arterial (LICA) administration of circulatory-derived autologous endothelial progenitor cells (EPCs) for improving the outcome in rat after acute ischemic stroke (IS). Methods and Results Adult-male SD rats (n=70) were equally categorized into group 1 (sham-operated control), group 2 (IS), group 3 (IS+EPCs/1.2x10 6 cells/by LICA administration 3h after IS), group 4 (IS+EPCs/LICA administration post-day-3 IS), group 5 (IS+EPCs/LICA administration post-day-7 IS), group 6 (IS+EPCs/LICA administration post-day 14-IS) and group 7 (IS+EPCs/LICA administration post-day-28 IS). The brain-infarct volume (at day 60/MRI) was lowest in group 1, highest in group 2 and significantly progressively increased from groups 3 to 7, whereas among the IS animals, the neurological function (i.e., by corner test) was significantly preserved in groups 3 to 6 than in groups 2 and 7 post-day-60 IS (all p<0.0001). By day 60, the endothelial markers at protein (CD31/vWF) and cellular levels (CD31+/vWF+), and number of small vessels exhibited an opposite pattern of BIV among the groups (all p<0.0001). The protein (IL-1ß/TNF-α/p-NF-κB/MMP-9) and cellular (GFAP+/microglial+) inflammatory levels, oxidative stress (NOX-1/NOX-2/oxidized protein/p22phox), autophagic (LC3B-III/LC3B-I/Beclin-1/Atg-5) and apoptotic (mitochondrial-Bax/caspase-3/PARP), were highest in group 2, lowest in group 1 and progressively increased from groups 3 to 7 (all p<0.0001). The angiogenesis biomarkers at protein (VEGF/SDF-1α/CXCR4) and cellular (SDF-1α+/CXCR4+) levels were significantly progressively increased from groups 1 to 3, then significantly progressively decreased from groups 3 to 7 (all p<0.0001).Conclusion Early EPC administration provided better benefits on improving functional/image/molecular-cellular outcomes after acute IS in rat.
The estimation of transmitted drug resistance mutation strains probability in the treatment of HIV using the Beta-Binomial model
Authors: Haankuku Urban , Njuho Peter
Published: February 2020

Background The human immunodeficiency virus (HIV) is a viral infection that destroys the human immune system resulting in acquired immunodeficiency syndrome (AIDS). The Zambia HIV prevalence rate is among the highest in the sub-Saharan Africa. With no HIV vaccine and cure for HIV/AIDS, the antiretroviral (ARV) therapy that slows the spread of the virus remains the only option. The administration of ARV has challenges of Transmitted Drug Resistance Mutation strains (TDRMs) in the treatment of HIV naïve patients. To address these challenges, we propose use of transition probabilities when prescribing a switch from first-line to second-line or to third-line regimen on ARV drugs combination. Methods We formulate a statistical technique for determining an optimal ARV drugs combination. Using data from the Zambia National Health Research Authority, we compute transition probability matrix chart on ARV therapy combination of the first and second baseline regimens using a Beta-Binomial Hierarchical model. We check parameter convergence using history and density plots, and check model adequacy using the deviation information criteria. Results The estimates converge to the fitted model as demonstrated by the history and density plots. The transition probability matrices corresponding to, TDF+ETC+NVP, TDF+FTC+EFV, AZT+3TC+NVP, AZT+3TC+EFV, D4T+3TC+NVP and D4T+3TC+EFV provide an upper triangular matrix of the probabilities. We observe a higher probability of remaining in the same regimen state than that of moving to another state. The computed transition probability matrix chart aid in deciding on the most effective combination to prescribe to a patient, in the presence of TDRM test results. Based on transition probabilities TDF+ETC+NVP, TDF+FTC+EFV, AZT+3TC+EFV and D4T+3TC+EFV cannot be prescribed to the patients who test K101 E and 115Y F strains. The available option to the patients’ remains either AZT + 3TC + NVP or D4T + 3TC + NVP. Combination AZT + 3TC + NVP with success probability of 0.97027 should be prescribed to the patient. Conclusion The transmission probabilities play a major role in aiding the physicians make an informed decision when prescribing an optimal drug combination. All newly diagnosed HIV individuals should have a TDRM test before any prescription on ARV therapy combination is made.
The Prevalence of Shiga toxin-1 in Shigella spp. Isolates Collected from Diarrhea Patients, Ahvaz, Iran
Authors: Mahdian Nahid , Gheysarzadeh Ali , Valadbeigi Hassan , Maleki Abbas , Sadeghifard Norkhoda
Published: February 2020

ObjectiveShigellosis as one of the substantial causative agents of microbial dysentery still has a remarkable prevalence in areas with poor hygienic infrastructures. The probable existence of the deadly Shiga toxin-1(Stx1) in some Shigella strains would manifest life-threatening clinical symptoms of the infection. The aim of this study was to determine the presence of Stx1 in isolated from patients with diarrhea. ResultsTotally, 227 Shigella species including 60 S. flexneri, 157 S. sonnei, and 10 S. boydii were collected from diarrheal patients in tropical infectious diseases research center of Ahvaz, Iran, from 2013 to 2015. The isolates were collected mostly from the intensive care unit, infectious disease, and surgery department. The isolates were identified and the polymerase chain reaction (PCR) was performed to detect the stx gene. The results indicated that none of them encode the stx gene. In conclusion, isolates of this study were not capable of stx1 encoding.
Locoregional recurrence patterns in women with breast cancer who have not undergone post-mastectomy radiotherapy
Authors: Zhao Xuran , Tang Yu , Wang Shulian , Yang Yong , Fang Hui , Wang Jianyang , Jing Hao , Zhang Jianghu , Sun Guangyi , Chen Siye , Jin Jing , Song Yongwen , Liu Yueping , Chen Bo , Qi Shunan , Li Ning , Tang Yuan , Lu Ningning , Ren Hua , Li Ye-Xiong
Published: February 2020

Background: To analyze the patterns of locoregional recurrence in breast cancer patients after mastectomy.Methods: The retrospective study included 7073 women with breast cancer without post-mastectomy radiotherapy: 4604 (65.1%) had pT1-2N0 disease (low risk); 2042 (28.9%), pT1-2N1 (intermediate risk); and 427 (6.0%), pT3-4 and/or pN2-3, or pT1-2N1 after neoadjuvant chemotherapy (high risk). The distribution of cumulative locoregional recurrence was analyzed. The local recurrence and regional recurrence rates were estimated by the Kaplan-Meier method, and differences were compared with the log-rank test. Multivariate analysis was performed using Cox logistic regression analysis.Results: In the median follow-up of 63.0 months, 469 patients had locoregional recurrence: chest wall recurrence in 238 cases (50.7%), supraclavicular/infraclavicular nodes in 236 (50.3%) cases, axilla in 92 (19.6%), and internal mammary nodes in 50 (10.7%) cases. The 5-year local recurrence and regional recurrence rates were 2.5% and 4.4%, respectively. Subgroup analysis of the three risk groups and five molecular subtypes (luminal A, luminal B-Her2 negative, luminal B-Her2 positive, Her2-enriched, and triple negative) also showed that the chest wall and supraclavicular/infraclavicular nodes were the most common recurrence sites. Age, tumor location, T stage, N stage, and hormone receptor status were independent prognostic factors for both local recurrence and regional recurrence (p < 0.05).Conclusions: The chest wall and supraclavicular/infraclavicular nodes are common sites of locoregional recurrence in breast cancer, irrespective of disease stage or molecular subtype, and the prognostic factors for local recurrence and regional recurrence are similar. Therefore, chest wall and supraclavicular/infraclavicular nodes irradiation should always be considered in post-mastectomy radiotherapy.
Ubiquitin specific peptidase 53 inhibits the occurrence and development of clear cell renal cell carcinoma through NF-κB pathway inactivation
Authors: Gui Dingwen , Dong Zhufeng , Peng Wei , Jiang Weidong , Huang Geng , Liu Gang , Ye Zhihua , Wang Yang , Xu Zuwei , Fu Jinlun , Luo Shuai , Zhao Yunfei
Published: February 2020

Background Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent malignant diseases in the urinary system with more than 140,000 related deaths annually. The lack of effective tumor biomarkers and understanding of the molecular mechanisms of this disease make the difficulty in the diagnosis and treatment. Ubiquitination-deubiquitination homeostasis is an important factor in ccRCC progression, ubiquitin specific peptidase 53 (USP53) belongs to the family of deubiquitinating enzymes, but its functions are rarely reported. Methods Databases obtained from GEO and TCGA were analyzed to reveal the role of USP53 in ccRCC. CCK-8/BrdU and EDU assays were used to detect the proliferation of ccRCC after USP53 overexpression or knockdown. Tumor xenograft experiment was used to verify the effect of clone formation of ccRCC after USP53 knockdown. Transwell assays were used to detect the metastasis of ccRCC after USP53 overexpression or knockdown. RNA sequencing and western blot analysis were employed to detect the change of genes after USP53 overexpression and knockdown. Results USP53 expression was down-regulated in ccRCC tissues and USP53 expression was significantly negative correlated with the tumor progression and clinical prognosis. The ability of growth and metastasis of ccRCC was inhibited after USP53 overexpression. And USP53 knockdown promoted ccRCC growth and metastasis. Moreover USP53 knockdown promoted the ability of clone formation of ccRCC in vivo . NF-κB signaling pathway significantly enriched and down regulated in USP53 overexpressed cells. And genes in the NF-κB pathway (such as IL1B, CXCL1-3, RELA, RELB, etc.) were obviously down regulated in USP53 overexpressed cells. USP53 overexpression decreased the phosphorylation of IKKβ and P65 in both Caki-1 and 786-O cells. And the expression of IκBα was increased. Phosphorylation of IKKβ and P65 was increased in both Caki-1 and 786-O cells after USP53 knockdown. Conclusion In summary, our data showed that USP53 inhibit ccRCC proliferation and metastasis through NF-κB pathway inactivation. The overexpression of USP53 is accompanied by changes in many inflammatory genes in the NF pathway. These findings may help better understand the pathogenesis of ccRCC and introduce new potential therapeutic targets for kidney cancer patients.
High-temperature requirement factor A1 rs11200638 polymorphism and age-related macular degenerative from a comprehensive analysis about 15316 subjects
Authors: Liu Ying , Jin Huipeng , Wei Dong , Li Wenxiu
Published: February 2020

Background The high-temperature requirement factor A1 (HTRA1) gene at the 10q26 locus has been associated with age-related macular degenerative (AMD) risk, with the significantly associated polymorphism being (rs11200638, -625G/A), however, above association is not consistent. We investigated an updated meta-analysis to evaluate the association between rs11200638 polymorphism and AMD risk thoroughly addressing this issue. Methods An identification was covered with the Pubmed and Chinese Wanfang databases through 27th Jan, 2020. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of associations. After a thorough and meticulous search, 35 different articles (33 case-control studies with HWE, 22 case-control studies about wet/dry AMD) were retrieved. Results Individuals carrying A-allele or AA genotype may have an increased risk to be AMD disease. For example, there has a significantly increased relationship between rs11200638 polymorphism and AMD both for Asians (OR: 2.50, 95%CI: 2.22-2.80 for A-allele vs. G-allele) and Caucasians (OR: 2.11, 95%CI: 1.43-3.13 for A-allele vs. G-allele). Moreover, a similar trend in the source of control subgroup was detected. To classify the type of AMD, increased association was also observed in both wet (OR: 3.40, 95%CI: 2.90-3.99 for dominant model) and dry (OR: 2.08, 95%CI: 1.24-3.48 for dominant model) AMD. Finally, based on the different genotyping methods, increased relationships were identified by sequencing, TaqMan, PCR-RFLP. Conclusions Our present meta-analysis suggests that the HTRA1 rs11200638 polymorphism are potentially associated with the risk of AMD development, especially about individuals carrying A-allele or AA genotype, who may be as identified targets to detect and intervene in advance. Further studies using larger sample sizes and including information about gene-environment interactions should be conducted to elucidate.
Whole-genome mate-pair sequencing of apparently balanced chromosome rearrangements reveals complex structural variations: two case studies
Authors: Tan Yaqi , Cheng Dehua , Tan Yue-Qiu
Published: February 2020

BACKGROUND: Apparently balanced chromosome rearrangements (ABCRs) in non-affected individuals are well-known to have high reproductive risks such as infertility, abnormal offspring, and pregnancy loss. However, caution should be exercised in genetic counseling and reproductive intervention because cryptic unbalanced defects and genome structural variations beyond the resolution of routine cytogenetics may get omitted.CASE PRESENTATION: Two cases of ABCRs were recruited in this study. In family 1, the couple suffered two terminated pregnancies and underwent labor induction. Single nucleotide polymorphism (SNP) array analysis of the aborted sample from the second pregnancy showed a 10.8 Mb heterozygous deletion at 10q26.13q26.3 and a 5.5 Mb duplication at 19q13.41-q13.43. The non-affected father was diagnosed as a carrier of three-way complex chromosomal rearrangement [t(6;10;19)(p22;q26;q13)] by karyotyping. Whole-genome mate-pair sequencing revealed a cryptic breakpoint on derivative (der) chromosome 19 indicating that the karyotype was a more complex structural rearrangement including four breakpoints. Three genes, FAM24B, CACNG8, and KIAA0556, were disrupted without causing any abnormal phenotype in the carrier. In family 2, the couple suffered from a spontaneous miscarriage. They had an affected child with multiple congenital malformations and an unbalanced karyotype, 46,XY,der(11)t(6;11)(q13;p11.2). The female partner was considered a balanced translocation carrier with the karyotype 46,XX,t(6;11)(q13;p11.2)dn. Further SNP array and fluorescent in situ hybridization (FISH) indicated a cryptic insertion between chromosome 6 and chromosome 11. Finally, whole-genome mate-pair sequencing revealed an extremely complex genomic structural variation, including a cryptic deletion and 12 breakpoints on derivative chromosome 11[der(11)], and 1 breakpoint on derivative chromosome 6 [der(6)].CONCLUSIONS: Our study investigated two rare cases of ABCRs and demonstrated that whole-genome mate-pair sequencing is a powerful approach to analyze the genome complex structural variation. In case of ABCRs detected by conventional cytogenetic techniques, whole genome sequencing (WGS) based approaches should be considered for accurate diagnosis, effective genetic counseling, and correct reproductive intervention to avoid recurrence risks.
The Role of NMDA receptors in rat propofol self-administration
Authors: Chen Bei ping , Huang Xi-xi , Dong Dong-mei , Wu Hui , Zhu Tian-qi , WANG Ben-fu
Published: February 2020

Aim

Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators of both neural plasticity and development, as well as of addiction and neurodegeneration. Herein we explored the role of these receptors in rat propofol self-administration.

Methods

Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using an FR fixed ratio schedule of the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, and then 10 minutes later were subjected to a propofol self-administration session. Results: After training, rats had acquired the ability to self-administer propofol successfully, as evidenced by a significant and stable rise in active nose-pokes leading to propofol administration relative to control nose-pokes (P<0.01) and became stable. Relative to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited significantly more propofol infusions (F(3, 28)=4.372, P<0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg. In addition, MK-801 failed to alter numbers of active (F(3, 28)=1.353, P>0.05) or inactive (F(3, 28)=0.047, P>0.05) responses in study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg (P=0.006, P<0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group exhibited a significant reduction in the number of active nose poke responses (F(3, 20)=20.8673, P<0.01) and the number of sucrose pellets (F(3, 20)=23.77, P<0.01), with increased locomotor activity (F(3, 20)=22.812, P<0.01).

Conclusion

These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.
Sahaj Samadhi Meditation versus a Health Enhancement Program for depression in chronic pain: protocol for a Randomized Controlled Trial and Implementation Evaluation
Authors: Sud Abhimanyu , Nelson Michelle L. A. , Cheng Darren K. , Armas Alana , Foat Kirk , Greiver Michelle , Hosseiny Fardous , Katz Joel , Moineddin Rahim , Mulsant Benoit H. , Newman Ronnie I. , Rivlin Leon , Vasudev Akshya , Upshur Ross
Published: February 2020

Background: Despite the high prevalence of comorbid chronic pain and depression, this comorbidity remains understudied. Meditation has demonstrated efficacy for both chronic pain and depression independently, yet there have been few studies examining its effectiveness when both conditions are present concurrently. Furthermore, while meditation is generally accepted as a safe and effective health intervention, little is known about how to implement meditation programs within or alongside the healthcare system. Methods: We will conduct a hybrid type 1 effectiveness-implementation evaluation. To measure effectiveness, we will conduct a randomized controlled trial (RCT) comparing Sahaj Samadhi Meditation (SSM) versus the Health Enhancement Program (HEP) in 160 people living with chronic pain, clinically significant depressive symptoms, and on long-term opioid therapy. Changes in depressive symptoms will be our primary outcome; pain severity, pain related function, opioid use, and quality of life will be the secondary outcomes. The primary endpoint will be at 12 weeks with a secondary endpoint at 24 weeks to measure sustainability of acute effects. Patients will be recruited from a community-based chronic pain clinic in a large urban centre in Mississauga, Canada. The meditation program will be delivered in the clinical environment where patients normally receive their chronic pain care by certified meditation teachers who are not regulated healthcare providers. We will use a mixed-methods design using the multi-level framework to understand the implementation of this particular co-location model. Discussion: Results of this hybrid evaluation will add important knowledge about the effectiveness of meditation for managing depressive symptoms in people with chronic pain. The implementation evaluation will inform both effectiveness outcomes and future program development, scalability, and sustainability.