bluuebunny/crossref_metadata_2025 huggingface dataset:
The First Study of Successful Pregnancies in Chinese patients with Phenylketonuria
Authors: Lin Wang , Fang Ye , Hui Zou , Kundi Wang , Zhihua Chen , Qin Hui , Bingjuan Han , Chun He , Xiaowen Li , Shen Ming
Published: October 2019

Background
Since the inception of newborn screening programs in China in the 1990s, pregnancy among patients with inherited, metabolic disorders has become more common. This study explores the management and outcomes of planned, full-term pregnancies in patients with phenylketonuria (PKU).
Method
Married patients with PKU from 2012 to 2017 were enrolled to receive prenatal counseling and regular health assessments. Study-related assessments included the timing of Phe-restricted diets, maternal weight gain, gestational age, pregnancy complications, and blood Phe concentrations (both pre-conception and during pregnancy), obstetrical data, and offspring outcomes(e.g.anthropomorphic measurements and developmental quotients [DQs]).
Results
A total of six offspring were successfully delivered. The mean±SD (range) age of the mother at delivery was 26.3±4.7 (range:21.1-32.5) years. The mean duration of Phe control before pregnancy was 5.5±1.3(range:3.1-6.5) months. During pregnancy, the proportion of blood Phe concentrations within the clinically-recommended target range (120–360μmol/L) ranged from 63.2-83.5%. Low birth weight (<2500g) offspring occurred in two women who experienced suboptimal metabolic control. In addition, offspring DQ was related to the proportion of blood Phe levels per trimester that were within the recommended range (r=0.886, p=0.016).
Conclusion
This is the first report of women in China with PKU who successfully gave birth to clinically healthy babies. Infant outcomes were related to maternal blood Phe management prior to and during pregnancy. In maternal PKU patients with poor compliance todietary treatment, sapropterin dihydrochloride（6R-BH 4 ）may be an option to improve the management of blood Phe levels.
Cost-effectiveness of two long-lasting insecticidal nets delivery models in mass campaign in rural Mozambique
Authors: Arroz Jorge , Candrinho Baltazar , Mendis Chandana , Lopez Melanie , Martins Maria do Rosário Oliveira
Published: October 2019

Objective The aim is to compare the cost-effectiveness of two long-lasting insecticidal nets (LLINs) delivery models (standard vs new) in universal coverage (UC) campaigns in rural Mozambique. Results The total financial cost of delivering LLINs was US$ 231,237.30 and US$ 174,790.14 in the intervention (302,648 LLINs were delivered) and control districts (219,613 LLINs were delivered), respectively. The average cost-effectiveness ratio (ACER) per LLIN delivered and ACER per household (HH) achieving UC was lower in the intervention districts. The incremental cost-effectiveness ratio (ICER) per LLIN and ICER per HH reaching UC were US$ 0.68 and US$ 2.24, respectively. Both incremental net benefit (for delivered LLIN and for HHs reaching UC) were positive (intervention deemed cost-effective). Overall, the newer delivery model was the more cost-effective intervention. However, the long-term sustainability of either delivery models is far from guaranteed in Mozambique’s current economic context.
Prevalence and associated factors of chronic kidney disease among adult hypertensive patients in Tigray teaching hospitals: A cross-sectional study
Authors: Bahrey Degena , Gebremedhn Gebreamlak , Mariye Teklewoini , Girmay Alem , Aberhe Woldu , Hika Assefa , Teklay Girmay , Tasew Hagos , Zeru Teklay , Gerensea Hadgu , Demoz Gebre Teklemariam
Published: October 2019

Objective: The aim of this study was to assess the prevalence of chronic kidney disease and to identify associated factors of chronic kidney disease among hypertensive patients. A cross-sectional study was conducted among selected five hundred seventy eight hypertensive patients. Data were collected using face to face interviewing questionnaires and from medical chart review. Binary logistic regression analyses were performed and analyzed using SPSS version 23.0.
Result: Of the total 578 hypertensive patients the prevalence of chronic kidney disease was found to be 128 ( 22.1%). Of these hypertensive patients, patients with uncontrolled blood pressure, overweight/obesity, dyslipidemia and diabetic mellitus, 43.3%, 33.7% , 27.3 % and 28.2 respectively. After adjustment, the independent variables the significant associated factors of chronic kidney disease among hypertensive patients were age [AOR (95% CI = 1.43 (1.07-1.81) ] , uncontrolled hypertension 4.434 [AOR ( 95%CI =9.45 (1.34, 14.73) ] , overweight/obese [AOR ( 95%CI =7.422 ( 2.72, 20.28) ] , dyslipidemia [AOR (95% CI) = 13.749 (5.69, 33.215)], diabetic mellitus [AOR (95% CI) = 2.137 (1.07, 4.26)]. In conclusion, the prevalence of chronic kidney disease was considerably high. The major associated factors of chronic kidney disease were age, uncontrolled hypertension, overweight/obese, diabetic mellitus and dyslipidemia.
Maternal H. pylori seropositivity is associated with gestational hypertension but irrelevant to fetal growth and development in early childhood
Authors: Lai Fu-Ping , Tu Yi-Fang , Sheu Bor-Shyang , Yang Yao-Jong
Published: October 2019

Background: Helicobacter pylori infection is known to alter growth-related hormones and cause growth faltering in young children. It is still unknown if maternal H. pylori infection has an impact on the levels of cord blood growth-related hormones and can predict intrauterine growth restriction and poor physical and neurodevelopmental outcomes in children. This study aimed to examine the associations between maternal H. pylori infection and pregnancy-related adverse events, fetal growth and early childhood development. Methods: The prospective cohort study recruited singleton pregnant women without major medical illnesses from January 2014 to January 2015. Seropositivity for H. pylori was defined by >12 U/ml of anti- H. pylori IgG in the maternal serum. Demographic data and pregnancy-related medical issues of the cohort were documented. Cord blood levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), insulin, and ghrelin were determined using ELISA test. The growth of eligible neonates was monitored annually for up to 3 years, and cognitive development was assessed using the comprehensive developmental inventory for infants and toddlers (CDIIT) test 3 years after birth. Results: Of the 106 enrolled women, 25 (23.6%) were H. pylori -seropositive. Maternal H. pylori seropositivity was correlated with a higher risk of developing gestational hypertension (GH) (12% vs. 1.2%, p =0.04) and lower cord blood levels of IGF-1 (<35 ng/ml, 70.0% vs. 40.7%, p =0.02) and IGFBP-3 (<1120 ng/ml, 100.0% vs. 76.3%, p =0.02) compared with the seronegative women. No significant impact on birth weight, childhood growth and cognitive development was found to correlate with maternal H. pylori seropositivity during pregnancy. Conclusions: Maternal H. pylori infection during pregnancy was more likely to develop GH, but not correlated with fetal and childhood growth and development. In addition to close monitoring of hypertension, H. pylori eradication can be considered for such H. pylori -infected mothers.
Trends and Distribution in Mortality Rates of Coronary Heart Disease in Hexi Corridor of Gansu in China from 2006 to 2015
Authors: li xinghui , ren xiaolan , qiao yan , xie ping , wang nan , nie fangfei , lei linfeng , wang chenchen , wang lijun , han junxian
Published: October 2019

Background: The mortality rate of coronary heart disease (CHD) in China is different from region to region, and there are sex, age and urban-rural differences. This study described trend and distribution of CHD in Hexi corridor of Gansu province from 2006 to 2015.
Method: The death data of CHD were obtained using the Death Reporting System of Gansu CDC for 2006-2015. The trend of the death cases of CHD by year, month and its distribution by sex, age and region were studied, and the changing characteristics of epidemiology was analyzed.
Results: Overall, The mortality rate of CHD in Hexi corridor showed a decline trend from 2006 to 2015, a tendency that higher in winter and spring, and lowest in summer.
The relative mortality of males was higher than that of females ( P < 0.05), increased with age ( P < 0.05), and that of rural areas was higher than that of urban areas ( P < 0.05). The trend analysis of death rate for ten-year showed a marked decline in females, an increase in 18-39 years old, a small change in 40-59 years old, a decrease in over 60 years old, and a downward tendency of urban areas. Further analysis showed that the mortality rate of males were higher than that of females in 18-39 years old and 40-59 years old group and also in urban areas group ( P < 0.05), while no sex difference in over 60 years old group and rural areas group ( P > 0.05).
Conclusion: The mortality of CHD in Hexi corridor of Gansu province in China was lower than the national average from 2006 to 2015, but increased gradually in specified population such as in males, young and middle-age, rural areas groups. The prevention and control measures should be strengthened in these special populations.
A prospective cohort study of maternal body mass index and maternal and neonatal outcomes in Fiji
Authors: Black Kirsten , Mudaliar Jyotishna , Nusair Pushpa , Rouse Ian
Published: October 2019

Background:
Maternal obesity is highly prevalent in Fiji and the perinatal and long-term consequences are likely to be significant. We investigated the relationship between maternal body mass index and maternal and neonatal outcomes and birth weight centiles in Fijian women.
Aims: We sought to use the Intergrowth 21 st (IG21) standard to record the proportion of babies born over the 90 th centile and to examine the association of other maternal and neonatal outcomes with normal weight, overweight and obesity amongst women presenting for antenatal care at the Colonial War Memorial Hospital in Fiji.
Methods: From January 2014 – December 2015 we undertook a prospective cohort study that used a structured questionnaire to collect data on women presenting for antenatal care. Body weight was recorded at the booking visit and adjusted to estimated pre-pregnancy bodyweight based on gestation at booking. Midwives collected follow up data regarding the outcomes of these pregnancies and we used the IG21 standard to estimate birthweight centiles.
Results: Of the 1397 records, 79 women were underweight and were excluded for detailed analysis. For the remaining 1318 cases detailed pregnancy and follow-up data were available. Compared to normal weight women overweight women were older, parous and were more likely to have pregnancy-related hypertension and were more likely to have an induction of labour. A sixth (n=224;16.7%) of the babies were above the 90 th centile of birthweight according to IG21 standard and as maternal BMI class increased, the odds of the baby’s birthweight being > 90 th centile increased. Compared to normal weight women, women with class II or II obesity were three times more likely to have a baby over the 90 th centile (AOR 3.053; CI 1.907-4.889).
Conclusions: A significant proportion of babies born in Fiji are large for gestational age which predisposes them to long term adverse metabolic health outcomes. Addressing maternal obesity before pregnancy is going to be key if Fiji is to curb the growing trend in child and adult obesity and metabolic disease in later life.
Genome-wide Survey of bHLH Super Gene Family in Brassica napus and Their Roles in Roots
Authors: Ke Yunzhuo , Wu Yunwen , Zhou Hongjun , Chen Ping , Wang Mangmang , Liu Mingming , Li Pengfeng , Yang Jing , Li Jiana , Du Hai
Published: October 2019

Background: Basic helix-loop-helix (bHLH) gene family is one of the largest transcription factors in plants and are functionally characterized in diverse species. However, less is known about their functions in the economically important allopolyploid oil crop, Brassica napus .
Results : We identified 602 potential bHLHs in B. napus genome ( BnbHLHs ) and categorized them into 36 subfamilies, including seven newly separated subfamilies, based on phylogeny, protein structure and exon-intron organization analysis. The intron insertion patterns of this gene family were corrected and a total of eight types were identified in the bHLH regions of BnbHLHs . Chromosome distribution and synteny analyses revealed that hybridization between Brassica rapa and Brassica oleracea was the main expansion mechanism for BnbHLHs . Expression analyses showed that BnbHLHs were wide and formed six main patterns, suggesting they may participate in various aspects in B. napus during the development. The expression profiles under five hormone treatments (IAA, ABA, ACC, GA3, 6-BA) in roots further revealed the active response of BnbHLHs with a large proportion of which being induced. qRT-PCR analysis confirmed the expression profiles of five candidate BnbHLHs under five hormone inductions. Up to 246 BnbHLHs from nine subfamilies were predicted to have potential roles relating to root development by joint analysis of expression profile and homolog function. Further, the MYB/bHLH/WD40 (MBW) protein complex regulating root hair development were verified in B. napus by yeast two-hybrid experiment.
Conclusion: The 602 BnbHLHs identified from B. napus could be classed into 36 subfamilies, and those members from the same subfamily generally have similar sequence motifs. BnbHLHs may widely involve in root biological process in B. napus . Overall, this study provides important insights into the characterization and potential functions of B. napus bHLH super gene family and thus will be useful in future gene function research.
Rationale and design of influence of volatile anesthesia versus total intravenous anesthesia on chronic postsurgical pain after cardiac surgery using Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials criteria assessment: study protocol for a prospective randomized controlled trial
Authors: Yu Hong , Zheng Jianqiao , Hua Yusi , Ren Shuofang , Yu Hai
Published: October 2019

Background Many patients develop chronic postsurgical pain (CPSP) after cardiac surgery, which interferes with sleep, mood and quality of life. Studies have suggested that propofol improved postoperative analgesia compared with volatile anesthetics, but the prevention effect on CPSP following cardiac surgery is still unknown. This study has been designed to compare the incidence in CPSP following cardiac surgery receiving volatile anesthesia compared to propofol-based total intravenous anesthesia (TIVA) using Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) criteria assessment.
Methods This is a prospective randomized controlled trial. Five hundred adult patients undergoing cardiac surgery will be randomly allocated to the volatile or the TIVA group. The volatile group will receive sevoflurane or desflurane during surgery to provide general anesthesia. The TIVA group will receive propofol-based intravenous agents and no volatile agents during surgery. The primary outcome will be the frequency of CPSP at 3 months, 6 months and 1 year after surgery. CPSP is defined as two ways: sternal and/or thoracic pain: (1) numeric rating scale, NRS >0; (2) meets all six IMMPACT criteria for CPSP assessed using validated pain instruments.
Discussion To our knowledge, this is the first prospective randomized protocol investigating the prevention of CPSP following cardiac surgery receiving volatile anesthesia compared to propofol-based TIVA using validated pain instruments in accordance with the IMMPACT recommendations. This study will provide important information on whether the choice of these two anesthetic regimens might influence CPSP after cardiac surgery.
Trial registration: Chictr.org.cn, ID ChiCTR1900020747. Registered on 16 January 2019.
Angiographic Features of Drug-Induced Bilateral Angle Closure and Transient Myopia with Ciliochoroidal Effusion
Authors: Kang Yong Koo , Son Byeong Jae , Park Dong Ho , Shin Jae Pil
Published: October 2019

Background: To report five cases of acute drug-induced bilateral angle closure and transient myopia with ciliochoroidal effusion, and to suggest a pathogenesis for this condition based upon angiography. Methods: This study is an observational case series. Five patients with acute drug-induced angle closure with ciliochoroidal effusion were examined by ultrasound biomicroscopy, fluorescein angiography, and indocyanine green angiography (ICGA). Results: Five patients presented with bilateral visual impairment and ocular pain after treatment with mefenamic acid, phendimetrazine tartrate, topiramate, or methazolamide. All patients presented a shallow anterior chamber and elevated intraocular pressure in both eyes. They showed a myopic shift from -0.5 to -17.0 diopters. Ultrasound biomicroscopy revealed annular ciliochoroidal effusions with diffuse thickening of the ciliary body in all cases. Rapid clinical improvement occurred in all patients after discontinuing the suspected drugs. ICGA findings were classified into two major signs (hypofluorescent dark spots and hyperfluorescent pinpoints) and three minor signs (early choroidal stromal vessel hyperfluorescence and leakage, diffuse hyperfluorescence of the choroid, and tortuous and dilated retinal vessels). Conclusions: The basic mechanism of pathogenesis involved an idiosyncratic reaction in uveal tissue to systemic drugs. Angiography showed that accumulation of extravascular fluid in the ciliochoroidal layer had a major role in pathogenesis. Angiography could therefore be a useful method to examine the pathophysiology of this condition by imaging of the choroidal layer.
Reducing shoulder complaints in employees with high occupational shoulder exposures: study protocol for a cluster-randomised controlled study (The Shoulder-Café Study)
Authors: Trøstrup Jeanette , Mikkelsen Lone Ramer , Frost Poul , Dalbøge Annett , Høybye Mette Terp , Casper Sven Dalgas , Jørgensen Lene Bastrup , Klebe Thomas Martin , Svendsen Susanne Wulff
Published: October 2019

Background: In Denmark, exercise therapy in combination with work modifications is the first choice treatment for persons with shoulder complaints and high occupational shoulder exposures. To obtain this treatment they must visit several healthcare providers, which makes usual care fragmented and uncoordinated. Therefore, we developed a new intervention which unifies the expertise that is needed. The main hypotheses are that a group-based Shoulder-Café intervention will more effectively reduce (I) shoulder complaints and (II) occupational shoulder exposures than an individual-based Shoulder-Guidance intervention (active control – enhanced usual care).
Methods: A cluster-randomised trial is conducted including 120 employees with high occupational shoulder exposures. Companies (clusters) are randomised to either Shoulder-Café or Shoulder-Guidance with a 1:1 allocation ratio. Participants are 18–65 years old and have an Oxford Shoulder Score (OSS) ≤ 40. Both interventions include a home-based shoulder exercise programme, assessment of shoulder exposures by technical measurements and self-report, and general information on how to reduce shoulder exposures. The Shoulder-Café course also includes three café meetings with physiotherapist-supervised exercises, clinical shoulder evaluation, education on shoulder anatomy, workplace-oriented counselling, and an opportunity for a workplace visit by a health and safety consultant. The primary outcomes are the OSS at 6 month follow-up (hypothesis I), and the mean number of minutes/day with the arm elevated > 60° shortly after end of intervention (hypothesis II). We will use mixed model analysis that allows for company clustering, and data will be analysed according to the intention-to-treat principle.
Discussion: Persons with shoulder complaints and high occupational shoulder exposures are an obvious target group for secondary prevention efforts. We developed the Shoulder-Café to reduce shoulder complaints and shoulder exposures while unifying the expertise that is needed to evaluate and treat shoulder complaints. If the intervention is effective, it would warrant widespread implementation.
Trial registration: The trial was registered at Clinicaltrials.gov on 18 May 2017 (ID: NCT03159910).
A Call for Consensus in Defining Efficacy in Clinical Trials for Opioid Addiction: Combined Results from a Systematic Review and Qualitative Study in Patients Receiving Pharmacological Assisted Therapy for Opioid Use Disorder
Authors: Dennis Brittany B. , Sanger Nitika , Bawor Monica , Naji Leen , Worster Andrew , Baptist-Mohseni Natasha , Hillmer Alannah , Rice Danielle , Corace Kim , Hutton Brian , Tugwell Peter , Thabane Lehana , Samaan Zainab
Published: October 2019

Background Given the complex nature of opioid addiction treatment and the rising number of available opioid substitution and antagonist therapies (OSAT), there is no ‘gold standard’ measure of treatment effectiveness, and each successive trial measures a different set of outcomes which reflect success in arbitrary or opportune terms.We sought to describe the variation in current outcomes employed across clinical trials for opioid addiction, as well as determine whether a discrepancy exists between the treatment targets that patients consider important and how treatment effectiveness is measured in the literature. Methods We searched nine commonly used databases (e.g. EMBASE, MEDLINE) from inception to August 1, 2015. Outcomes used across trials were extracted and categorized according to previously established domains. To evaluate patient reported goals of treatment, semi-structured interviews were conducted with 18 adults undergoing methadone treatment. Results We identified 60 trials eligible for inclusion. Once outcomes were categorized into eight broad domains (e.g. abstinence/substance abuse), we identified 21 specific outcomes with furthermore 53 subdomains and 118 measurements. Continued opioid use and treatment retention were the most commonly reported measures (46%, n=28). The majority of patients agreed that abstinence from opioids was a primary goal in their treatment, however they also stressed goals under-reported in clinical trials. Conclusion There is inconsistency in the measures used to evaluate the effectiveness of OSATs. Individual and population level decision making is being guided by a standard of effect considered useful to researchers yet in direct conflict with what patients deem important. PROSPERO ID CRD42013006507
Peripapillary retinal artery in first diagnosed and untreated normal tension glaucoma
Authors: RONG XIN , Cai Yu , Li Mei , Fang Yuan , Tian Tian , Pan Yingzi
Published: October 2019

Background Glaucoma, an important cause of visual impairment in many countries, remains a common eye condition due to difficulties in its early diagnosis. We analyzed the characteristics of retinal arteries to add a valuable technology for helping the normal tension glaucoma (NTG) diagnosis.
Methods This study included 51 patients with newly diagnosed NTG with hemifield defects and 60 age-matched controls. Peripapillary retinal arteriolar calibers (PRACs) photoed by non-mydriatic retinal camera were measured using ImageJ by two masked readers. We also performed spectral-domain optical coherence tomography to evaluate retinal nerve fiber layer thickness (RNFLT) and optic disc parameters. Their relations to retinal arteriolar calibers were investigated by univariate and multivariate linear regression. The area under the receiver operating characteristic curve (AUROC) was used to confirm the powers to detect NTG by PRACs.
Results PRACs in four quadrants were significantly reduced in individuals with first diagnosed NTG (82 ± 15.1 μm, 80 ± 13.6 μm, 71 ± 11.6 μm, and 64 ±10.0 μm) compared with those in age-matched controls (101 ± 9.8 μm, 105 ± 8.7 μm, 90 ± 7.5 μm, and 82 ± 9.8 μm). Superotemporal and inferotemporal PRACs in the visual field-affected hemifield were narrower than those in the unaffected hemifield in NTG group ( P ≤0.004). Temporal PRACs in the RNFL unaffected hemifield were significantly narrower than in healthy eyes ( P <0.001). Superotemporal PRAC showed a significant correlation with superior RNFLT (β=0.659, P <0.001), and a similar relationship was found between inferotemporal PRAC and inferior RNFLT (β=0.227, P =0.015). The diagnostic capability of temporal PRACs was satisfactory (superotemporal PRAC; AUROC 0.983, cut-off value 84.7 μm, inferotemporal PRAC; AUROC 0.946, cut-off value 94.2 μm).
Conclusions PRAC and infero temporal PRAC are valid parameters for discriminating patients with NTG.
Functional versus functional and anatomical criteria-guided ranibizumab treatment in patients with neovascular age-related macular degeneration – results from the randomized, phase IIIb OCTAVE study
Authors: Staurenghi Giovanni , Garweg Justus G. , Gerendas Bianca S. , Macfadden Wayne , Gekkiev Boris , Margaron Philippe , Dunger-Baldauf Cornelia , Kolář Petr
Published: October 2019

Background

To evaluate the efficacy and safety of two individualized ranibizumab retreatment schemes in neovascular age-related macular degeneration.Methods

Patients (N=671) were randomized (1:1) to receive three initial monthly ranibizumab 0.5 mg injections, then retreatment guided by either best-corrected visual acuity (BCVA) loss (Group I) or BCVA loss and/or signs of disease activity on optical coherence tomography (OCT; Group II). The study was terminated prematurely, as OCT-guided disease activity monitoring became a recommended retreatment criteria. Efficacy analyses were performed on patients who completed 12 months of the originally planned 24-month study. Safety analyses are presented for all safety analyzable patients.Results

Of 671 randomized patients, 305 completed 12 months of the study. For the 12-month completers, baseline mean (standard deviation) BCVA and reading-center evaluated central subfield thickness (CSFT) were comparable [Group I: 60.9 (13.10) letters and 517.7(201.79) µm; Group II: 60.2 (12.21) letters and 515.3 (198.37) µm]. The change from baseline at Month 12 in BCVA was 6.7 (13.48) letters in Group I and 8.3 (13.53) letters in Group II and the change in CSFT was −161.3 (163.48) µm and −175.3 (170.45) µm, respectively. The mean number of ranibizumab injections was 8.2 in Group I and 8.4 in Group II.Conclusion

Ranibizumab treatment resulted in visual and anatomic gains at 12 months for both retreatment strategies, with a trend in favor of OCT-guided vs BCVA loss guided retreatment. No new safety signals were seen.
Evaluating the Cerebrospinal Fluid ctDNA detection by Next-Generation Sequencing in the diagnosis of Meningeal Carcinomatosis
Authors: Zhao Yue , He Jun-Ying , Zou Yue-Li , Guo Xiao-Su , Cui Jun-Zhao , Guo Li , Bu Hui
Published: October 2019

Background

Meningeal carcinomatosis (MC) is the most severe form of brain metastasis and causes significant morbidity and mortality. Currently, the diagnosis of MC is routinely confirmed on the basis of clinical signs and symptoms, positive cerebrospinal fluid (CSF) cytology, and/or neuroimaging (contrast-enhanced brain MRI and/or CT) features. However, negative rate of CSF cytology and neuroimaging findings often result in a failure to diagnose MC from the patients who actually have the disease.Methods

A total of 35 CSF samples were collected from 35 patients with MC for CSF cytology examination, CSF tumor-derived circulating tumor DNA (ctDNA) extraction and cancer-associated gene mutations detection by next-generation sequencing (NGS) at the same time.Results

The most frequent primary tumor in this study was lung cancer (26/35, 74%), followed by gastric cancer (2/35, 6%), breast cancer (2/35, 6%), prostatic cancer (1/35, 3%), parotid gland carcinoma (1/35, 3%) and lymphoma (1/35, 3%) while no primary tumor could be found in the remaining 2 patients in spite of using various inspection methods. Twenty-five CSF samples (25/35; 71%) were found neoplastic cells in CSF cytology examination while all of the 35 CSF samples (35/35; 100%) were revealed having detectable ctDNA in which cancer-associated gene mutations were detected. All of 35 patients with MC in the study underwent contrast-enhanced brain MRI and/or CT and 22 neuroimaging features (22/35; 63%) were consistent with MC. The sensitivity of the neuroimaging was 88% (95% confidence intervals [95% CI], 75 to 100) (p=22/25) and 63% (95% CI, 47 to 79) (p=22/35) compared to those of CSF cytology and CSF ctDNA, respectively. The sensitivity of the CSF cytology was 71% (95% CI, 56 to 86) (n=25/35) compared to that of CSF ctDNA.Conclusions

This study suggests a higher sensitivity of CSF ctDNA than those of CSF cytology and neuroimaging findings. We find cancer-associated gene mutations in ctDNA from CSF of patients with MC at 100% of our cohort, and utilizing CSF ctDNA as liquid biopsy technology based on the detection of cancer-associated gene mutations may give additional information to diagnose MC with negative CSF cytology and/or negative neuroimaging findings.
Integrated mRNA and miRNA transcriptome analysis reveals a regulatory network for tuber expansion in Chinese yam (Dioscorea opposite)
Authors: Zhou Yun-Yi , Luo Shuzhen , Hameed Saba , Xiao Dong , Zhan Jie , Wang Aiqing , He Longfei
Published: October 2019

Background
Yam tuber is a storage organ, derived from the modified stem. Tuber expansion is a complex process, and depends on the expressions of genes that can be influenced by environmental and endogenous factors. However, little is known about the regulatory mechanism of tuber expansion. In order to identify genes and miRNAs involved in tuber expansion, we examined the mRNAs and small RNAs in Dioscorea opposite (Chinese yam) cv. Guihuai 16 tuber during its initiation and expansion stages.
Results
A total of 14238 differentially expressed genes in yam tuber at its expansion stage were identified by using RNA sequencing technology. Among them, 5723 genes were up-regulated, and 8515 genes were down-regulated. Functional analysis revealed the coordination of tuber plant involved in processes of cell events, metabolism, biosynthesis, and signal transduction pathways at transcriptional level, suggesting that these differentially expressed genes are somehow involved in response to tuber expansion, including CDPK, CaM, CDL, SAUR, DELLA, SuSy, and expansin. In addition, 541 transcription factor genes showed differential expression during the expansion stage at transcriptional level. MADS, bHLH, and GRAS were involved in cell differentiation, division, and expansion, which may relate to tuber expansion. Noteworthy, data analysis revealed that 22 known tuber miRNAs belong to 10 miRNA families, and 50 novel miRNAs were identified. The integrated analysis of miRNA-mRNA showed that 4 known miRNAs and 11 genes formed 14 miRNA-target mRNA pairs were co-expressed in expansion stage. miRNA160, miRNA396, miRNA535 and miRNA5021 may be involved in complex network to regulate cell division and differentiation in yam during its expansion stage.
Conclusion
The mRNA and miRNA datasets presented here identified a subset of candidate genes and miRNAs that are putatively associated with tuber expansion in yam, a hypothetical model of genetic regulatory network associated with tuber expansion in yam was put forward, which may provide a foundation for molecular regulatory mechanism researching on tuber expansion in Dioscorea species.
Study on availability of groundwater resources in Selangor state of Malaysia for an efficient planning and management of water resources
Authors: Mridha Goutam Chandra , Hossain M. Monowar , Uddin Mohammad Salah , Masud Md. Sohel
Published: October 2019

Groundwater has become an important source of water to meet the increasing requirement for domestic, industrial, and agricultural needs. The study was formulated to assess the availability of groundwater resources in Selangor State, Malaysia. An integrated MIKE SHE and MIKE 11-based surface water–groundwater interaction model was developed to fulfill the study objectives. Model results illustrated that groundwater flows from the eastern part of the hilly region to the western part and ultimately discharges into the sea. The study also revealed that Sungai Langat, Sungai Klang, and Sungai Selangor receive water from groundwater and do not feed the groundwater. Approximate potential groundwater resources based on water balance study varies from 860–960 million liter per day (MLD), 630–690 MLD, 810–870 MLD to 630–690 MLD for Langat basin, Klang basin, Selangor basin, and Bernam basin, respectively. Impacts due to extreme dry condition showed that groundwater table declined about 0.5–3 m in most of the area. However, groundwater level for the major portion of Selangor State will drop to about 0–1 m for increased abstraction due to changed land-use pattern. Study findings may be used for a holistic and comprehensive management of groundwater resources for sustainable development in Selangor State, Malaysia.
Treatment for high-concentration liquid crystal wastewater with a novel Fenton–SBR–microwave pyrolysis integrated process
Authors: Li Jincheng , Zhao Baoxiu , Ji Qingpeng , Zhang Yanqing , Zhang Kaixin , Gou Tianshuo , Xia Wenxiang , Liu Jie
Published: October 2019

A novel Fenton–SBR–microwave pyrolysis integrated process is developed to treat liquid crystal wastewater possessing complex components, high toxicity and strong stability. In this integrated process, Fenton–SBR and microwave pyrolysis are for the removal of chemical oxygen demand (COD) and disposal of iron mud generated in the Fenton process respectively. The effects of H2O2:Fe2+ molar ratio and Fenton dosage on COD removal were optimized. The experimental results revealed that the removal efficiencies for COD and total organic carbon (TOC) were 99.8% and 99.2%, and the values for MLSS and SVI were stable at 4,500 mg L–1 and 65%, respectively. Microscopic examination proved that there were rotifer, Epistylis galea, Opercularia coarctata, vorticella and mormon genus which are indicative microbes for good water quality. Iron mud waste produced in the Fenton reaction was handled with microwave pyrolysis, producing ɑ-Fe2O3 commercial byproduct. The estimated cost including chemical reagents and electricity for this integrated process is about $320 T–1, without consideration of the added value of the ɑ-Fe2O3 byproduct. TOC removals in the Fenton and SBR processes both fit well with pseudo-first-order kinetics and the corresponding half-life times are 0.15 and 7 h, respectively.
Advances in Pharmacological Activities and Mechanisms of Glycyrrhizic Acid
Authors: Chen Kun , Yang Rong , Shen Fa-Qian , Zhu Hai-Liang
Published: October 2019

Licorice (Glycyrrhiza glabra L.) is widely regarded as an important medicinal plant and has
been used for centuries in traditional medicine because of its therapeutic properties. Studies have
shown that metabolites isolated from licorice have many pharmacological activities, such as antiinflammatory,
anti-viral, participation in immune regulation, anti-tumor and other activities. This article
gives an overview of the pharmacological activities and mechanisms of licorice metabolites and the
adverse reactions that need attention. This review helps to further investigate the possibility of licorice
as a potential drug for various diseases. It is hoped that this review can provide a relevant theoretical
basis for relevant scholars’ research and their own learning.
Extracellular Vesicles as Therapeutics for Brain Injury and Disease
Authors: Upadhya Dinesh , Shetty Ashok K.
Published: October 2019

:

Extracellular vesicles (EVs) are gaining tremendous importance in comprehending central nervous
system (CNS) function and treating neurological disorders because of their role in intercellular communication
and reparative processes, and suitability as drug delivery vehicles. Since EVs have lipid membranes, they cross
the blood-brain barrier easily and communicate with target neurons and glia even deep inside the brain. EVs from
various sources have been isolated, characterized, and tailored for promoting beneficial effects in conditions, such
as brain injury and disease. Particularly, EVs isolated from mesenchymal stem cells and neural stem cells have
shown promise for alleviating brain dysfunction after injury or disease. Such properties of stem cell-derived EVs
have great importance for clinical applications, as EV therapy can avoid several concerns typically associated
with cell therapy. This minireview confers the competence of EVs for improving brain function by modulating
CNS injury and disease.
Nanoparticle-Mediated Drug Delivery: Blood-Brain Barrier as the Main Obstacle to Treating Infectious Diseases in CNS
Authors: Gondim Brenna Louise Cavalcanti , da Silva Catarino Jonatas , de Sousa Marlos Aureliano Dias , de Oliveira Silva Mariana , Lemes Marcela Rezende , de Carvalho-Costa Tamires Marielem , de Lima Nascimento Tatiana Rita , Machado Juliana Reis , Rodrigues Virmondes , Oliveira Carlo José Freire , Cançado Castellano Lúcio Roberto , da Silva Marcos Vinicius
Published: October 2019

Background:

Parasitic infections affecting the central nervous system (CNS) present high morbidity
and mortality rates and affect millions of people worldwide. The most important parasites affecting the CNS are
protozoans (Plasmodium sp., Toxoplasma gondii, Trypanosoma brucei), cestodes (Taenia solium) and free-living
amoebae (Acantamoeba spp., Balamuthia mandrillaris and Naegleria fowleri). Current therapeutic regimens
include the use of traditional chemicals or natural compounds that have very limited access to the CNS, despite
their elevated toxicity to the host. Improvements are needed in drug administration and formulations to treat these
infections and to allow the drug to cross the blood-brain barrier (BBB).

Methods:

This work aims to elucidate the recent advancements in the use of nanoparticles as nanoscaled drug
delivery systems (NDDS) for treating and controlling the parasitic infections that affect the CNS, addressing not
only the nature and composition of the polymer chosen, but also the mechanisms by which these nanoparticles
may cross the BBB and reach the infected tissue.

Results:

There is a strong evidence in the literature demonstrating the potential usefulness of polymeric nanoparticles
as functional carriers of drugs to the CNS. Some of them demonstrated the mechanisms by which drugloaded
nanoparticles access the CNS and control the infection by using in vivo models, while others only describe
the pharmacological ability of these particles to be utilized in in vitro environments.

Conclusion:

The scarcity of the studies trying to elucidate the compatibility as well as the exact mechanisms by
which NDDS might be entering the CNS infected by parasites reveals new possibilities for further exploratory
projects. There is an urgent need for new investments and motivations for applying nanotechnology to control
parasitic infectious diseases worldwide.
Current Advances in the Synthesis and Biological Evaluation of Pharmacologically Relevant 1,2,4,5-Tetrasubstituted-1H-Imidazole Derivatives
Authors: Rossi Renzo , Ciofalo Maurizio
Published: October 2019

:

In recent years, the synthesis and evaluation of the biological properties of 1,2,4,5-tetrasubstituted-1H-imidazole derivatives have been the subject of a large number of studies by academia and industry. In these studies it has been shown that this large and highly differentiated class of heteroarene derivatives includes high valuable compounds having important biological and pharmacological properties such as antibacterial, antifungal, anthelmintic, anti-inflammatory, anticancer, antiviral, antihypertensive, cholesterol-lowering, antifibrotic, antiuricemic, antidiabetic, antileishmanial and antiulcer activities.

:

The present review with 411 references, in which we focused on the literature data published mainly from 2011 to 2017, aims to update the readers on the recent developments on the synthesis and biological evaluation of pharmacologically relevant 1,2,4,5-tetrasubstituted-1H-imidazole derivatives with an emphasis on their different molecular targets and their potential use as drugs to treat various types of diseases. Reference was also made to substantial literature data acquired before 2011 in this burgeoning research area.
Assessment of miR-212 and Other Biomarkers in the Diagnosis and Treatment of HBV-infection-related Liver Diseases
Authors: Zhang Yigan , Xi Huaze , Nie Xin , Zhang Peng , Lan Ning , Lu Ying , Liu Jinrong , Yuan Wenzhen
Published: October 2019

Objective:

Our study aims to detect the sensitivity of the new biomarker miR-212 existing in serum exosomes along with other hepatocellular carcinoma biomarkers such as AFP (alpha-fetoprotein), CA125 (carbohydrate antigen-ca125), and Hbx protein in the diagnosis of HBV-related liver diseases. We also aim to study the roles of these biomarkers in the progression of chronic hepatitis B and provide scientific data to show the clinical value of these biomarkers.

Methods:

We selected 200 patients with HBV-infection (58 cases of chronic hepatitis B, 47 cases of hepatocellular carcinoma, 30 cases of compensatory phase cirrhosis, and 65 cases of decompensatory phase cirrhosis), 31 patients with primary liver cancer without HBV infection, and 70 healthy individuals as the control group. The expression level of serum AFP and CA125 was detected with electrochemiluminescence immunoassay. The expression level of the Hbx protein was detected with ELISA. Meanwhile, the expression level of miR-212 in serum was analyzed with RT-qPCR. We collected patients’ clinical information following the Child-Pugh classification and MELD score criterion, and statistical analysis was made between the expression level of miR-212 and the collected clinical indexes. Lastly, we predicted the target genes of the miR-212 and its functions using bioinformatics methods such as cluster analysis and survival prediction.

Results:

Compared to the control group, the expression level of miR-212 in HBV infected patients was remarkably increased (P<0.05), especially between the HBV-infection Hepatocellular carcinoma group and the non-HBVinfection liver cancer group (P<0.05). The expression of miR-212 was increased in patients’ Child-Pugh classification, MELD score, and TNM staging. Moreover, the sensitivity and specificity of miR-212 were superior to AFP, CA125, and HBx protein.

Conclusion:

There is a linear relationship between disease progression and expression level of miR-212 in the serum of HBV infected patients. This demonstrates that miR-212 plays a significant role in liver diseases. miR-212 is expected to be a new biomarker used for the diagnosis and assessment of patients with HBV-infection-related liver diseases.
Synthesis and Biological Activity of Hydrazones and Derivatives: A Review
Authors: de Oliveira Carneiro Brum Juliana , França Tanos Celmar Costa , LaPlante Steven R. , Villar José Daniel Figueroa
Published: October 2019

Hydrazones and their derivatives are very important compounds in medicinal chemistry due
to their reported biological activity for the treatment of several diseases, like Alzheimer’s, cancer, inflammation,
and leishmaniasis. However, most of the investigations on hydrazones available in literature
today are directed to the synthesis of these molecules with little discussion available on their biological
activities. With the purpose of bringing lights into this issue, we performed a revision of the literature
and wrote this review based on some of the most current research reports of hydrazones and derivatives,
making it clear that the synthesis of these molecules can lead to new drug prototypes. Our
goal is to encourage more studies focused on the synthesis and evaluation of new hydrazones, as a contribution
to the development of potential new drugs for the treatment of various diseases.
Use of Chou’s 5-Steps Rule to Reveal Active Compound and Mechanism of Shuangshen Pingfei San on Idiopathic Pulmonary Fibrosis
Authors: Chen Yeqing , Fan Xinsheng
Published: October 2019

Background:

Shuangshen Pingfei San (SPS) is the derivative from the
classic formula Renshen Pingfei San in treating idiopathic pulmonary fibrosis (IPF).

Methods:

In this study, Chou’s 5-steps rule was performed to explore the potential
active compound and mechanism of SPS on IPF. Compound–target network, target–
pathway network, herb–target network and the core gene target interaction network
were established and analyzed. A total of 296 compounds and 69 candidate therapeutic
targets of SPS in treating IPF were obtained. Network analysis revealed that the main
active compounds were flavonoids (such as apigenin, quercetin, naringenin, luteolin),
other clusters (such as ginsenoside Rh2, diosgenin, tanshinone IIa), which might also
play significant roles. SPS regulated multiple IPF relative genes, which affect fibrosis
(PTGS2, KDR, FGFR1, TGFB, VEGFA, MMP2/9) and inflammation (PPARG, TNF, IL13,
IL4, IL1B, etc.).

Conclusion:

In conclusion, anti-pulmonary fibrosis effect of SPS might be related to the
regulation of inflammation and pro-fibrotic signaling pathways. These findings revealed
that the potential active compounds and mechanisms of SPS on IPF were a benefit to
further study.
Dance for People with Alzheimer’s Disease: A Systematic Review
Authors: Ruiz-Muelle Alicia , López-Rodríguez María Mar
Published: October 2019

Background:

In recent years, several reviews have addressed the effectiveness of dance therapy in dementia, healthy older adults, or the elderly in general. However, reviews regarding the effect of this therapy exclusively on patients diagnosed with Alzheimer’s disease have not been found.

Objective:

The purpose of this study is to review the available literature describing clinical trials which explore the effects of dancing on psychological and physical outcomes, functionality, cognitive function, and quality of life in patients diagnosed with Alzheimer’s disease. In addition, this review aims to assess the quality of studies that perform dance therapy interventions in these patients.

Methods:

This study is a systematic review of randomized and non-randomized clinical trials regarding the effect of intervention including a dancing activity in people diagnosed with Alzheimer's disease.

Results:

In total, the evidence for this review rests on 12 studies with a total of 349 participants. The findings of this mini-review confirm the positive effect of dance therapy on physical and cognitive function, functionality, psychological outcomes, and quality of life in people with Alzheimer's disease.

Conclusion:

Most of the studies implementing dance as part of the therapeutic treatment has shown to improve or slow the worsening in the quality of life of patients with Alzheimer's disease and their caregivers. Future research focused on these patients should use a more exhaustive methodology and make a more detailed description of these kind of interventions.