bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a compound heterozygote in LYST gene: a case report on Chediak-Higashi syndrome
Authors: Song Yinsen , Dong Zhengping , Luo Shuying , Yang Junmei , Lu Yuebing , Gao Bo , Fan Tianli
Published: January 2020

Background

Chediak-Higashi Syndrome (CHS) is a rare autosomal recessive disease caused by loss of function of the lysosomal trafficking regulator protein. The causative gene LYST/CHS1 was cloned and identified in 1996, which showed significant homology to other species such as bovine and mouse. To date, 74 pathogenic or likely pathogenic mutations had been reported.

Case presentation

Here we describe a compound heterozygote in LYST gene, which was identified in a 4-year-old female patient. The patient showed skin hypopigmentation, sensitivity to light, mild splenomegaly and reduction of platelets in clinical examination. Giant intracytoplasmic inclusions were observed in the bone marrow examination, suggesting the diagnosis of CHS. Amplicon sequencing was performed to detect pathogenic mutation in LYST gene. The result was confirmed by two-generation pedigree analysis base on sanger sequencing.

Conclusion

A compound heterozygote in LYST gene, consisting of a missense mutation c.5719A > G and an intron mutation c.4863-4G > A, was identified from the patient by using amplicon sequencing. The missense mutation is reported for the first time. Two-generation pedigree analysis showed these two mutations were inherited from the patient’s parents, respectively. Our result demonstrated that amplicon sequencing has great potential for accelerating and improving the diagnosis of rare genetic diseases.
Association between serotonin 2A receptor (HTR2A) genetic variations and risk of hypertension in a community-based cohort study
Authors: Choi Jung Ran , Jeon Minhee , Koh Sang Baek
Published: January 2020

Background

Hypertension is one of the risk factors for obesity-related cardiovascular diseases. We investigated whether genetic variations in serotonin 2A receptor (HTR2A) were associated with hypertension.

Methods

We carried out a cross-sectional study in cohorts A (Ansan-Ansung cohort, N = 6039) and B (Wonju-Pyengchang cohort, N = 7524). Several genetic variants in HTR2A including rs7330636, rs9590999, rs2183057, and rs4942595 were selected and genotyped.

Results

In hypertensive participants in cohort A, the baseline systolic blood pressure and body mass index were 141.80 ± 17.20 mg/dL and 24.48 ± 4.75 kg/m2, respectively, which were higher than in those without hypertension (p < 0.001). rs4942595TC genotype was associated with hypertension in cohort A (OR = 0.739), after adjusting for variables. Subjects with rs4942578AA genotype had a decreased risk of hypertension after adjusting for clinical factor (OR = 0.735) in cohort B, and an elevated risk of hypertension in cohort A (OR = 1.562). The logistic regression analysis showed that participants with rs4941573TC genotype were 1.327 times more likely to have a higher blood pressure than those with TT genotype (95% CI 1.101–1.599) in cohort B. Whereas, the OR for developing hypertension in subjects with rs17069883CC genotype compared to those with AA genotype was 1.447 (95% CI 1.018–2.056; p for trend = 0.040) in cohort A.

Conclusions

HTR2A genetic variations were associated with hypertension risk in our study.
Increased levels of XPA might be the basis of cisplatin resistance in germ cell tumours
Authors: Cierna Zuzana , Miskovska Vera , Roska Jan , Jurkovicova Dana , Pulzova Lucia Borszekova , Sestakova Zuzana , Hurbanova Lenka , Machalekova Katarina , Chovanec Michal , Rejlekova Katarina , Svetlovska Daniela , Kalavska Katarina , Kajo Karol , Babal Pavel , Mardiak Jozef , Ward Thomas A. , Mego Michal , Chovanec Miroslav
Published: January 2020

Background

Germ cell tumours (GCTs) represent a highly curable malignity as they respond well to cisplatin (CDDP)-based chemotherapy. Nevertheless, a small proportion of GCT patients relapse or do not respond to therapy. As this might be caused by an increased capacity to repair CDDP-induced DNA damage, identification of DNA repair biomarkers predicting inadequate or aberrant response to CDDP, and thus poor prognosis for GCT patients, poses a challenge. The objective of this study is to examine the expression levels of the key nucleotide excision repair (NER) factors, XPA, ERCC1 and XPF, in GCT patients and cell lines.

Methods

Two hundred seven GCT patients’ specimens with sufficient follow-up clinical-pathological data and pairwise combinations of CDDP-resistant and -sensitive GCT cell lines were included. Immunohistochemistry was used to detect the ERCC1, XPF and XPA protein expression levels in GCT patients’ specimen and Western blot and qRT-PCR examined the protein and mRNA expression levels in GCT cell lines.

Results

GCT patients with low XPA expression had significantly better overall survival than patients with high expression (hazard ratio = 0.38, 95% confidence interval: 0.12–1.23, p = 0.0228). In addition, XPA expression was increased in the non-seminomatous histological subtype, IGCCCG poor prognosis group, increasing S stage, as well as the presence of lung, liver and non-pulmonary visceral metastases. Importantly, a correlation between inadequate or aberrant CDDP response and XPA expression found in GCT patients was also seen in GCT cell lines.

Conclusions

XPA expression is an additional independent prognostic biomarker for stratifying GCT patients, allowing for improvements in decision-making on treatment for those at high risk of refractoriness or relapse. In addition, it could represent a novel therapeutic target in GCTs.
Effect of adjuvant chemotherapy on survival benefit in stage III colon cancer patients stratified by age: a Japanese real-world cohort study
Authors: Kawamura Hidetaka , Morishima Toshitaka , Sato Akira , Honda Michitaka , Miyashiro Isao
Published: January 2020

Background

Adjuvant chemotherapy is relatively underused in older patients with colon cancer in Japan, and its age-specific effects on clinical outcomes remain unclear. This study aimed to assess the effect of adjuvant chemotherapy on survival benefit in stage III colon cancer patients stratified by age in a Japanese real-world setting.

Methods

In this multi-center retrospective cohort study, we analyzed patient-level information through a record linkage of population-based cancer registry data and administrative claims data. The study population comprised patients aged ≥18 years who received a pathological diagnosis of stage III colon cancer and underwent curative resection between 2010 and 2014 at 36 cancer care hospitals in Osaka Prefecture, Japan. Patients were divided into two groups based on age at diagnosis (< 75 and ≥ 75 years). The effect of adjuvant chemotherapy was analyzed using Cox proportional hazards regression models for all-cause mortality with inverse probability weighting of propensity scores. Adjusted hazard ratios were estimated for both age groups.

Results

A total of 783 patients were analyzed; 476 (60.8%) were aged < 75 years and 307 (39.2%) were aged ≥75 years. The proportion of older patients who received adjuvant chemotherapy (36.8%) was substantially lower than that of younger patients (73.3%). In addition, the effect of adjuvant chemotherapy was different between the age groups: the adjusted hazard ratio was 0.56 (95% confidence interval: 0.33–0.94, P = 0.027) in younger patients and 1.07 (0.66–1.74, P = 0.78) in older patients.

Conclusions

The clinical effectiveness of adjuvant chemotherapy in older patients with stage III colon cancer appears limited under current utilization practices.
Therapeutic effect against retinal neovascularization in a mouse model of oxygen-induced retinopathy: bone marrow-derived mesenchymal stem cells versus Conbercept
Authors: Xu Wei , Cheng Weijing , Cui Xiaoyuan , Xu Guoxing
Published: January 2020

Background

To study the therapeutic effect of bone marrow-derived mesenchymal stem cells (BMSC) against retinal neovascularization and to compare with anti-vascular endothelial growth factor (VEGF) therapy.

Methods

Neonatal C57BL/6 mice were exposed in hyperoxygen and returned to room air to develop oxygen-induced retinopathy (OIR). Red fluorescent protein-labeled BMSC and Conbercept were intravitreally injected into OIR mice, respectively. Inhibition of neovascularization and apoptosis in OIR mice were assessed through retinal angiography, histopathology and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.

Results

BMSC were able to migrate and integrate into the host retina, significantly inhibit retinal neovascular tufts and remodel the capillary network after injecton. Treatment with BMSC increased the retinal vascular density, decreased the number of acellular capillaries and inhibited retinal cell death. This effect was not inferior to current anti-VEGF therapy by using Conbercept.

Conclusions

Intravitreal injection of BMSC exerts a protective effect against retinal neovascularization and offers a therapeutic strategy for oxygen-induced retinopathy.
Knowledge of glaucoma and associated factors among adults in Gish Abay town, Northwest Ethiopia
Authors: Yenegeta Zewdu , Tsega Ayanaw , Addis Yezinash , Admassu Fisseha
Published: January 2020

Background

Glaucoma is a global public health problem and it is the leading cause of irreversible blindness worldwide. Even though public knowledge of glaucoma is a key for early case identification and prevention of blindness, it is unknown in the study area, making provision of interventions difficult. Therefore, this study was intended to assess knowledge of glaucoma and associated factors among adults in Gish Abay town, Northwest Ethiopia, 2018.

Methods

A Community based cross - sectional design study with systematic random sampling technique was used to select 630 adults. The study was conducted from April to May, 2018. Data was entered into Epi Info version 7 and was analysed by Statistical Package for Social Sciences version 23. Binary logistic regression model and adjusted odds ratio with 95% confidence level was used to identify the significant factors associated with knowledge of glaucoma. Variables with P–value ≤0.05 was considered statistically significant.

Results

About 594 adults were participated with a response rate of 94%. Above half of (52%) the participants were females with median age of 28 years. The proportion of good knowledge was demonstrated in 16.8% [95% CI; 14.0, 19.9]. Educational status: primary education [AOR; 2.89: 1.41, 5.90], secondary education [AOR; 3.03: 1.47, 6.24] college and above [AOR; 5.18: 2.21, 12.13], history of eye examination [AOR; 6.52: 3.37, 12.63]; family history of glaucoma [AOR; 12.08: 4.13, 35.30] and higher income level [AOR; 3.11: 1.55, 6.25] were positively associated with good knowledge of glaucoma.

Conclusions

The proportion of good knowledge of glaucoma was low. Higher educational status, positive family history of glaucoma, eye examination and higher income level were significantly associated with knowledge of glaucoma.
Impact of an educational workshop on psychiatrists’ attitude towards psychosomatic medicine
Authors: Baessler Franziska , Ciprianidis Anja , Wagner Fabienne Louise , Zafar Ali , Kanellopoulos Thanos , Baumann Tabea Chiara , Sandmann Clara-Louisa , Schultz Jobst-Hendrik
Published: January 2020

Background

Although psychosomatic medicine is not recognised as a medical specialisation globally, it has proven useful for treating many disorders in Germany. This paper reports on the impact of an educational workshop as a tool for raising awareness about psychosomatic medicine among international psychiatrists.

Methods

Psychiatrists from eight different countries were educated on psychosomatic medicine and psychotherapy during a 90-min workshop using a video, a slide presentation and an innovative teaching format called ‘speed coaching’. Learning outcomes were assessed by analysing questionnaires completed by the participants before and after the workshop.

Results

Half of the participants who initially rejected the notion that psychosomatic medicine should be a specialisation on its own changed their minds in favour for it to be a separate discipline (p = 0.125). Awareness about which diseases and patients psychosomatic doctors deal with was increased. The intent for treatment of patients with eating disorders by a psychosomatic physician quadrupled among the participants (p = 0.004).

Conclusions

A brief educational intervention can influence psychiatrists’ decisions to opt for approaches by doctors specialized in psychosomatics for certain disorders. Further studies may explore why psychiatrists agree or disagree that psychosomatic medicine should be a separate specialisation on its own.
C-reactive protein mediates the association between leisure-time physical activity and lung function in middle-aged and older adults
Authors: Chen Meng , Huang Chuanying , Feng Wenjing , Li Yujie , Wu Yili
Published: January 2020

Background

Although previous studies have reported the benefits of physical activity (PA) to lung function in middle-aged and older adults, the biological mechanisms are still unclear. This study aimed to assess the extent to which C-reactive protein (CRP) mediates the association between leisure-time PA and lung function.

Methods

A population-based sample was recruited from English Longitudinal Study of Ageing (ELSA), Wave 6 (2012–2013). PA was self-reported by questionnaires. CRP was analyzed from peripheral blood. Lung function parameters including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured by using a spirometer. Baron and Kenny’s causal steps method and multiple linear regression models based on the Karlson/Holm/Bree (KHB) method were used to assess the mediating effect.

Results

Among 6875 participants, 28.4% were classified into low PA, 49.8% into moderate PA, and 21.8% into high PA. Multiple linear regression models suggested that higher PA was associated with lower levels of CRP (β = − 0.048, P = 0.002 for moderate PA; β = − 0.108, P < 0.001 for high PA). CRP negatively correlated with FEV1 (β = − 0.180, P < 0.001) and FVC (β = − 0.181, P < 0.001). Higher levels of PA were associated with better FEV1 (β = 0.085, P < 0.001 for moderate PA; β = 0.150, P < 0.001 for high PA) and FVC (β = 0.131, P < 0.001 for moderate PA; β = 0.211, P < 0.001 for high PA). After introducing the CRP into the models, regression coefficients of PA with FEV1 (β = 0.077, P < 0.001 for moderated PA; β = 0.130, P < 0.001 for high PA) and FVC (β = 0.123, P < 0.001 for moderated PA; β = 0.188, P < 0.001 for high PA) decreased. The indirect effect of high PA on lung function via CRP was significant, with 9.42–12.99% of the total effect being mediated.

Conclusions

The association between PA and lung function is mediated by CRP, suggesting that this association may be partially explained by an inflammation-related biological mechanism. This finding highlights the possible importance of PA in systemic inflammation and lung function, thus, middle-aged and older adults should be encouraged to enhance PA levels.
Neonatal mortality and associated factors in the specialized neonatal care unit Asmara, Eritrea
Authors: Andegiorgish Amanuel Kidane , Andemariam Mihreteab , Temesghen Sabela , Ogbai Liya , Ogbe Zemichael , Zeng Lingxia
Published: January 2020

Background

Limited knowledge on the magnitude of neonatal mortality and associated factors is hampering early intervention in African countries.

Objective: To determine neonatal mortality and associated factors in the Specialized Neonatal Care Unit Asmara, Eritrea.

Methods

Medical records of all neonates admitted to the Specialized Neonatal Care Unit in 2016 were reviewed using a cross-sectional study. The most important causes of admission and mortality were analyzed. Univariate and multivariate logistic regression analysis was used to evaluate the strength of risk factors associated with neonatal mortality. Variables significant at P < 0.20 level in the univariate analysis were retained in the multivariate model. Model fit was evaluated using Hosmer and Lemeshow test (Chi-square = 12.89, df = 8; P = 0.116), implies the model’s estimates fit the data at an acceptable level. Collinearity was assessed using variance inflation factor (VIF) < 4. P-value < 0.05 was considered statistically significant.

Results

Of the 1204 (59.9% boys and 40.1% girls) neonates admitted in 2016, 79 (65.6/1000 live births) died. The major causes of admission were sepsis (35.5%), respiratory distress syndrome (15.4%) and perinatal asphyxia (10%). Major causes of death were respiratory distress syndrome (48.1%); extremely low birth weight (40.9%) and very low birth weight (30.5%). After adjustment, low birth weight (Adjusted odds ratio (AOR) = 4.55, 95% CI,1.97–10.50), very low birth weight (AOR = 19.24, 95% CI, 5.80–63.78), late admission (24 h after diagnosis) (AOR = 2.96, 95% CI, 1.34–6.52), apgar score (in 1 min AOR = 2.28, 95% CI, 1.09–4.76, in 5 min AOR = 2.07, 95% CI, 1.02–4.22), and congenital abnormalities (AOR = 3.95, 95% CI, 1.59–9.85) were significantly associated with neonatal mortality. Neonates that stayed > 24 h in the Specialized Neonatal Care Unit (AOR = 0.23, 95% CI, 0.11–0.46) had a lower likelihood of death. Overall 95.8% of mothers of neonates attended antenatal care and 96.6% were facility delivered. None of the maternal conditions were associated with neonatal mortality in this study.

Conclusions

Low birth weight, late admission, low apgar scores and congenital abnormalities were significantly associated with neonatal mortality in the Specialized Neonatal Care Unit. Early management of low birth weight, preterm births, and neonatal complications should be the priority issues for controlling local neonatal deaths.
Neighborhood socioeconomic disadvantage is associated with multimorbidity in a geographically-defined community
Authors: Chamberlain Alanna M. , Finney Rutten Lila J. , Wilson Patrick M. , Fan Chun , Boyd Cynthia M. , Jacobson Debra J. , Rocca Walter A. , St. Sauver Jennifer L.
Published: January 2020

Background

Persons with low socioeconomic status may be disproportionately at risk for multimorbidity.

Methods

Adults aged ≥20 years on 4/1/2015 from 7 counties in Minnesota were identified using the Rochester Epidemiology Project (population-based sample). A composite measure of neighborhood socioeconomic disadvantage, the area deprivation index (ADI), was estimated at the census block group level (n = 251). The prevalence of 21 chronic conditions was obtained to calculate the proportion of persons with multimorbidity (≥2 chronic conditions) and severe multimorbidity (≥5 chronic conditions). Hierarchical logistic regression was used to estimate the association of ADI with multimorbidity and severe multimorbidity using odds ratios (OR).

Results

Among 198,941 persons (46.7% male, 30.6% aged ≥60 years), the age- and sex-standardized (to the United States 2010 census) median prevalence (Q1, Q3) was 23.4% (21.3%, 25.9%) for multimorbidity and 4.8% (4.0%, 5.7%) for severe multimorbidity. Compared with persons in the lowest quintile of ADI, persons in the highest quintile had a 50% increased risk of multimorbidity (OR 1.50, 95% CI 1.39–1.62) and a 67% increased risk of severe multimorbidity (OR 1.67, 95% CI 1.51–1.86) after adjusting for age, sex, race, and ethnicity. Associations were stronger after further adjustment for individual level of education; persons in the highest quintile had a 78% increased risk of multimorbidity (OR 1.78, 95% CI 1.62–1.96) and a 92% increased risk of severe multimorbidity (OR 1.92, 95% CI 1.72–2.13). There was evidence of interactions between ADI and age, between ADI and sex, and between ADI and education. After age 70 years, no difference in the risk of multimorbidity was observed across quintiles of ADI. The pattern of increasing multimorbidity with increasing ADI was more pronounced in women. Finally, there was less variability across quintiles of ADI for the most highly educated group.

Conclusions

Higher ADI was associated with increased risk of multimorbidity, and the associations were strengthened after adjustment for individual level of education, suggesting that neighborhood context plays a role in health above and beyond individual measures of socioeconomic status. Furthermore, associations were more pronounced in younger persons and women, highlighting the importance of interventions to prevent chronic conditions in younger women, in particular.
Cross-sectional study of associations between normal body weight with central obesity and hyperuricemia in Japan
Authors: Shirasawa Takako , Ochiai Hirotaka , Yoshimoto Takahiko , Nagahama Satsue , Watanabe Akihiro , Yoshida Reika , Kokaze Akatsuki
Published: January 2020

Background

Several studies have shown that normal weight with central obesity (NWCO) is associated with cardiovascular disease risk factors such as hypertension, dyslipidemia and diabetes. However, the relationship between NWCO and hyperuricemia has not been studied in detail.

Methods

We investigated the association between NWCO and hyperuricemia among Japanese adults aged 40–64 years who had undergone periodic health examinations between April 2013 and March 2014. Obesity was defined as a body mass index (BMI) ≥25 kg/m2 and central obesity was determined as a waist-to-height ratio (WHtR) ≥0.5. We classified the participants into the following groups based according to having obesity and central obesity: normal weight (BMI 18.5–24.9 kg/m2) without (NW; WHtR < 0.5) and with (NWCO) central obesity, and obesity without (OB) and with (OBCO) central obesity. Hyperuricemia was defined as serum uric acid > 7.0 and ≥ 6.0 mg/dL in men and women, respectively, or under medical treatment for hyperuricemia. Alcohol intake was classified as yes (daily and occasional consumption) and none (no alcohol consumption). Odds ratios (OR) and 95% confidence intervals (CI) for hyperuricemia were calculated using a logistic regression model.

Results

We analyzed data derived from 96,863 participants (69,241 men and 27,622 women). The prevalences of hyperuricemia in men and women were respectively, 21.4 and 11.0%, and of participants with NWCO respectively 15.6 and 30.0%. The adjusted OR for hyperuricemia was significantly increased in OBCO compared with NW, regardless of sex (men: OR, 2.12; 95%CI; 2.03–2.21; women: OR, 3.54; 95%CI, 3.21–3.90) and were statistically significant in NWCO compared with NW (men: OR, 1.44; 95%CI, 1.36–1.52; women: OR, 1.41; 95%CI, 1.27–1.57). The results were similar regardless of alcohol consumption.

Conclusions

We found that NWCO and OBCO were associated with hyperuricemia in middle-aged Japanese men and women. Middle-aged Japanese adults with normal weight but having central obesity should be screened using a combination of BMI and WHtR and educated about how to prevent hyperuricemia.
Association between early childhood caries and poverty in low and middle income countries
Authors:   the ECCAG, Folayan Morenike Oluwatoyin , El Tantawi Maha , Aly Nourhan M. , Al-Batayneh Ola B. , Schroth Robert J. , Castillo Jorge L. , Virtanen Jorma I. , Gaffar Balgis O. , Amalia Rosa , Kemoli Arthur , Vulkovic Ana , Feldens Carlos A.
Published: January 2020

Background

The aim of this study was to assess the relationship between early childhood caries (ECC) in 3–5-year-old children, seven indicators of poverty and the indicator of monetary poverty in low- and middle-income countries (LICs, MICs).

Methods

This ecologic study utilized 2007 to 2017 country-level data for LICs and MICs. Explanatory variables were seven indicators of poverty namely food, water, sanitation, health, shelter, access to information, education; and monetary poverty. The outcome variable was the percentage of 3–5-year-old children with ECC. A series of univariate general linear regression models were used to assess the relationship between the percentage of 3–5 year-old children with ECC and each of the seven indicators of poverty, and monetary poverty. This was followed by multivariable regression models to determined the combined effect of the seven indicators of poverty, as well as the combined effect of the seven indicators of poverty and monetary poverty. Adjusted R2measured models’ ability to explain the variation among LICs and MICs in the percentage of 3–5-year-old children with ECC.

Results

Significantly more people had food, sanitation, shelter, access to information, education and monetary poverty in LICs than in MICs. There was no difference in the prevalence of ECC in 3–5-year-old children between LICs and MICs. The combination of the seven indicators of poverty explained 15% of the variation in the percentage of 3–5-year-old children with ECC compared to 1% explained by monetary poverty. When the seven indicators of poverty and the indicator for monetary poverty were combined, the amount of variation explained by them was 10%. Only two of the poverty indicators had a direct relationship with the percentage of children with ECC; there was a higher percentage of ECC in countries with higher percentage of population living in slums (B = 0.35) and in those countries with higher percentage of the population living below poverty lines (B = 0.19). The other indicators had an inverse relationship.

Conclusion

The use of multiple indicators to measures of poverty explained greater amount of variation in the percentage of 3–5-year-olds with ECC in LICs and MICs than using only the indicator for monetary poverty.
Evaluation of apoptosis and angiogenesis in ectopic and eutopic stromal cells of patients with endometriosis compared to non-endometriotic controls
Authors: Delbandi Ali-Akbar , Mahmoudi Mahmoud , Shervin Adel , Heidari Sahel , Kolahdouz-Mohammadi Roya , Zarnani Amir-Hassan
Published: January 2020

Background

Endometriosis is a chronic, painful, and inflammatory disease characterized by extra-uterine growth of endometrial tissues. Increased angiogenesis and resistance to apoptosis have been suggested to be involved in pathogenesis and development of endometriosis. The objective of this study was to examine apoptosis potential and angiogenesis contribution of eutopic (EuESCs) and ectopic (EESCs) endometrial stromal cells in patients with endometriosis compared to endometrial stromal cells from non-endometriotic controls (CESCs).

Methods

Stromal cells were isolated by enzymatic digestion of ectopic (n = 11) and eutopic (n = 17) endometrial tissues from laparoscopically-confirmed endometriotic patients. Endometrial stromal cells of 15 non-endometriotic patients served as control. Following cell characterization by immunofluorescent staining and flow cytometry using a panel of antibodies, the total RNA was isolated from the cultured cells, and analyzed for the expression of genes involved in apoptosis (Bcl-2, Bcl-xL, Bax, and caspase-3) and angiogenesis [vascular endothelial growth factor-A (VEGF-A) and hepatocyte growth factor (HGF)] by Real-time PCR.

Results

Significantly higher gene expression levels of Bcl-2 and Bcl-xL were found in EESCs compared with EuESCs and CESCs (p < 0.01). The gene expression of Bax in EESCs, EuESCs, and CESCs was not statistically significant. Furthermore, EuESCs exhibited a significantly lower caspase-3 gene expression compared with CESCs (p < 0.01) or EESCs (p < 0.05). Regarding angiogenesis, VEGF-A gene expression in EESCs (p < 0.001) and EuESCs (p < 0.05) were significantly higher compared with those of CESCs. EESCs exhibited a significantly higher HGF gene expression compared with EuESCs (p < 0.05).

Conclusions

These findings suggest reduced propensity to apoptosis and increased angiogenesis potential of EESCs, which may be involved in pathogenesis of endometriosis.
A new concordant partial AUC and partial c statistic for imbalanced data in the evaluation of machine learning algorithms
Authors: Carrington André M. , Fieguth Paul W. , Qazi Hammad , Holzinger Andreas , Chen Helen H. , Mayr Franz , Manuel Douglas G.
Published: January 2020

Background

In classification and diagnostic testing, the receiver-operator characteristic (ROC) plot and the area under the ROC curve (AUC) describe how an adjustable threshold causes changes in two types of error: false positives and false negatives. Only part of the ROC curve and AUC are informative however when they are used with imbalanced data. Hence, alternatives to the AUC have been proposed, such as the partial AUC and the area under the precision-recall curve. However, these alternatives cannot be as fully interpreted as the AUC, in part because they ignore some information about actual negatives.

Methods

We derive and propose a new concordant partial AUC and a new partialcstatistic for ROC data—as foundational measures and methods to help understand and explain parts of the ROC plot and AUC. Our partial measures are continuous and discrete versions of the same measure, are derived from the AUC and c statistic respectively, are validated as equal to each other, and validated as equal in summation to whole measures where expected. Our partial measures are tested for validity on a classic ROC example from Fawcett, a variation thereof, and two real-life benchmark data sets in breast cancer: the Wisconsin and Ljubljana data sets. Interpretation of an example is then provided.

Results

Results show the expected equalities between our new partial measures and the existing whole measures. The example interpretation illustrates the need for our newly derived partial measures.

Conclusions

The concordant partial area under the ROC curve was proposed and unlike previous partial measure alternatives, it maintains the characteristics of the AUC. The first partial c statistic for ROC plots was also proposed as an unbiased interpretation for part of an ROC curve. The expected equalities among and between our newly derived partial measures and their existing full measure counterparts are confirmed. These measures may be used with any data set but this paper focuses on imbalanced data with low prevalence.

Future work

Future work with our proposed measures may: demonstrate their value for imbalanced data with high prevalence, compare them to other measures not based on areas; and combine them with other ROC measures and techniques.
Biomedical drugs and traditional treatment in care seeking pathways for adults with epilepsy in Masindi district, Western Uganda: a household survey
Authors: Rutebemberwa Elizeus , Ssemugabo Charles , Tweheyo Raymond , Turyagaruka John , Pariyo George William
Published: January 2020

Background

Many patients with epilepsy in sub-Saharan Africa do not receive adequate treatment. The purpose of the study was to identify the health care providers where patients with epilepsy sought care and what treatment they received.

Methods

A cross sectional study was conducted across 87 out of 312 villages in Masindi district. A total of 305 households having patients with epilepsy were surveyed using an interviewer administered questionnaire. Data was entered and analysed in Epi-info ver 7 for univariate and bivariate analysis, and in Stata SE ver 15.0 for multivariable analysis. Sequences of health providers consulted in care seeking, rationale and drugs used, and factors associated with choice of provider were assessed.

Results

A total of 139 out of 305 (45.6%) households offered some treatment regimen at home when patients got symptoms of epilepsy with 44.6% (62/139) giving herbs and 18.0% (25/139) offering prayers. Eight different types of providers were consulted as first contact providers for treatment of epilepsy. Health centres received the highest percentage 35.4% (108/305) followed by hospitals 20.9% (64/305). A total of 192 of 305 (63.0%) households received anti-epileptic drugs, 13.1% (40/305) received prayers and 21.6% (66/305) received herbs at the first contact care seeking. Compared to a health centre as the first choice provider, other facilities more significantly visited were; hospitals if they were perceived as nearer (adj. Coeff 2.16, 95%CI 0.74, 3.59, p = 0.003), churches / mosques if cure for epilepsy was expected (adj. Coeff 1.91, 95%CI 0.38, 3.48, p = 0.014), and traditional healer for those aged ≥46 years (adj. Coeff 5.83, 95%CI 0.67, 10.99, p = 0.027), and friends/neighbour for traders (adj. Coeff 2.87, 95%CI 0.71, 5.04, p = 0.009).

Conclusion

Patients with epilepsy seek treatment from multiple providers with the public sector attending to the biggest proportion of patients. Engaging the private sector and community health workers, conducting community outreaches and community sensitization with messages tailored for audiences including the young, older epileptics, traditional healers as stakeholders, and traders could increase access to appropriate treatment for epilepsy.
Experience gained from the implementation of the Saudi TraumA Registry (STAR)
Authors: FORD Jane E. , ALQAHTANI Abdulrahman S. , ABUZINADA Shatha A. A. , CAMERON Peter A. , FITZGERALD Mark C. , ALENIZI Ahmed S. , FARJOU Dina
Published: January 2020

Background

Trauma registries are essential to trauma systems, to enable collection of the data needed to enhance clinical knowledge and monitor system performance. The King Saud Medical City (KSMC) in Riyadh, Kingdom of Saudi Arabia (KSA) is aiming to become a Level 1 Trauma Centre, and required a trauma registry in order to do so. Our objective was to establish the Saudi TraumA Registry (STAR) at the (KSMC) and ready it for national deployment. The challenge was that no formal trauma data collection had occurred previously and clinicians had no prior experience of trauma registries.

Methods

To develop the registry, a novel 12 step implementation plan was created and followed at the KSMC. Registry criteria and a Minimum Dataset were selected; training was delivered; database specifications were written; operating procedures were developed and regular reporting was initiated.

Results

Data collection commenced on August 1st 2017. The registry was fully operational by April 2018, eight months ahead of schedule. During the first year of data collection an average of 216 records per month were entered into the database. An inaugural report was presented at the Saudi Trauma Conference in February 2019.

Conclusions

The strategy deployed at the KSMC has successfully established the STAR. In the short term, process indicators will track the development of the hospital into a Level 1 Trauma Centre. In the medium to long term the STAR will be rolled out nationally to capture the impact of public health initiatives aimed at reducing injury in the KSA. The effect of the STAR will be that the country is better equipped to deliver continuous improvements in trauma systems and quality of care.
Multi-level transcriptome sequencing identifies COL1A1 as a candidate marker in human heart failure progression
Authors: Hua Xiumeng , Wang Yin-Ying , Jia Peilin , Xiong Qing , Hu Yiqing , Chang Yuan , Lai Songqing , Xu Yong , Zhao Zhongming , Song Jiangping
Published: January 2020

Background

Heart failure (HF) has been recognized as a global pandemic with a high rate of hospitalization, morbidity, and mortality. Although numerous advances have been made, its representative molecular signatures remain largely unknown, especially the role of genes in HF progression. The aim of the present prospective follow-up study was to reveal potential biomarkers associated with the progression of heart failure.

Methods

We generated multi-level transcriptomic data from a cohort of left ventricular heart tissue collected from 21 HF patients and 9 healthy donors. By using Masson staining to calculate the fibrosis percentage for each sample, we applied lasso regression model to identify the genes associated with fibrosis as well as progression. The genes were further validated by immunohistochemistry (IHC) staining in the same cohort and qRT-PCR using another independent cohort (20 HF and 9 healthy donors). Enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma level in a validation cohort (139 HF patients) for predicting HF progression.

Results

Based on the multi-level transcriptomic data, we examined differentially expressed genes [mRNAs, microRNAs, and long non-coding RNAs (lncRNAs)] in the study cohort. The follow-up functional annotation and regulatory network analyses revealed their potential roles in regulating extracellular matrix. We further identified several genes that were associated with fibrosis. By using the survival time before transplantation,COL1A1was identified as a potential biomarker for HF progression and its upregulation was confirmed by both IHC and qRT-PCR. Furthermore, COL1A1 content ≥ 256.5 ng/ml in plasma was found to be associated with poor survival within 1 year of heart transplantation from heart failure [hazard ratio (HR) 7.4, 95% confidence interval (CI) 3.5 to 15.8, Log-rankpvalue < 1.0 × 10− 4].

Conclusions

Our results suggested that COL1A1 might be a plasma biomarker of HF and associated with HF progression, especially to predict the 1-year survival from HF onset to transplantation.
A systematic review of surgical margins utilized for removal of cutaneous mast cell tumors in dogs
Authors: Selmic Laura E. , Ruple Audrey
Published: January 2020

Background

Traditionally, wide lateral surgical margins of 3 cm and one fascial plane deep have been recommended for resection of canine cutaneous mast cell tumor (MCT). Several studies have been published assessing surgical margins of less than this traditional recommendation. The objective of this systematic review was to determine if resection MCT with lateral surgical margins < 3 cm results in low rates of incomplete resection and local tumor recurrence. Systematic searches of digital bibliographic databases were performed with two authors (AR & LES) screening abstracts to identify relevant scientific articles. Studies regarding surgical treatment of dogs with cutaneous MCT were reviewed. Data abstraction was performed and the quality of individual studies and the strength of the body of evidence for utilization of surgical margins < 3 cm for removal of MCTs was assessed.

Results

From the initial 78 citations identified through the database searches, four articles were retained for data abstraction after both relevance screenings were performed. Two studies were retrospective observational studies, one was a prospective case series and one was a prospective clinical trial. Assessment of the quality level of the body of evidence identified using the GRADE system was low. Excision of MCT at 2 cm and 3 cm was associated with comparably low rates of incomplete excision and recurrence.

Conclusions

Despite the low quality of the overall body of evidence, a recommendation can be made that resection of canine cutaneous MCTs (< 4 cm) of Patnaik grade I and II with 2 cm lateral margins and 1 fascial plane deep results in low rates of incomplete excision and local tumor recurrence.
Melatonin restores Muc2 depletion induced by V. vulnificus VvpM via melatonin receptor 2 coupling with Gαq
Authors: Lee Young-Min , Park Jong Pil , Jung Young Hyun , Lee Hyun Jik , Kim Jun Sung , Choi Gee Euhn , Han Ho Jae , Lee Sei-Jung
Published: January 2020

Background

Melatonin (5-methoxy-N-acetyltryptamine), a hormone produced in the pineal gland, has a variety of biological functions as an antioxidant, but a functional role of melatonin in the regulation of intestinal mucin (Muc) production during bacterial infection has yet to be described in detail. In this study, we investigate the effects of melatonin during Muc2 repression elicited by the Gram-negative bacterium V. vulnificus.

Methods

Mucus-secreting human HT29-MTX cells were used to study the functional role of melatonin during Muc2 depletion induced by the recombinant protein (r) VvpM produced by V. vulnificus. The regulatory effects of melatonin coupling with melatonin receptor 2 (MT2) on the production of reactive oxygen species (ROS), the activation of PKCδ and ERK, and the hypermethylation of the Muc2 promoter as induced by rVvpM were examined. Experimental mouse models of V. vulnificus infection were used to study the role of melatonin and how it neutralizes the bacterial toxin activity related to Muc2 repression.

Results

Recombinant protein (r) VvpM significantly reduced the level of Muc2 in HT29-MTX cells. The repression of Muc2 induced by rVvpM was significantly restored upon a treatment with melatonin (1 μM), which had been inhibited by the knockdown of MT2 coupling with Gαq and the NADPH oxidase subunit p47 phox. Melatonin inhibited the ROS-mediated phosphorylation of PKCδ and ERK responsible for region-specific hypermethylation in the Muc2 promoter in rVvpM-treated HT29-MTX cells. In the mouse models of V. vulnificus infection, treatment with melatonin maintained the level of Muc2 expression in the intestine. In addition, the mutation of the VvpM gene from V. vulnificus exhibited an effect similar to that of melatonin.

Conclusions

These results demonstrate that melatonin acting on MT2 inhibits the hypermethylation of the Muc2 promoter to restore the level of Muc2 production in intestinal epithelial cells infected with V. vulnificus.
Up-regulation of circ_LARP4 suppresses cell proliferation and migration in ovarian cancer by regulating miR-513b-5p/LARP4 axis
Authors: Lin Wumei , Ye Haiyan , You Keli , Chen Le
Published: January 2020

Background

Ovarian cancer (OC) is a common fatal malignant tumor of female reproductive system worldwide. Growing studies have proofed that circular RNAs (circRNAs) engage in the regulation of various types of cancers. However, the underlying biological functions and effect mechanism of circular RNA_LARP4 (circ_LARP4) in OC have not been explored.

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to detect the expression of circ_LARP4 in OC cells. The function of circ_LARP4 was measured by cell counting kit-8 (CCK-8), colony formation assay and transwell assay. RNA immunoprecipitation (RIP) assay and luciferase reporter assays assessed the binding correlation between miR-513b-5p and circ_LARP4 (or LARP4).

Results

The expression of circ_LARP4 in OC cells was much lower than that in human normal ovarian epithelial cells. Overexpressing circ_LARP4 impaired cell proliferation, invasion and migration abilities. Circ_LARP4 worked as a competing endogenous RNA (ceRNA) to sponge miR-513b-5p. Furthermore, LARP4 was indirectly modulated by circ_LARP4 as the downstream target of miR-513b-5p, as well as the host gene of circ_LARP4.

Conclusion

Circ_LARP4 could hamper cell proliferation and migration by sponging miR-513b-5p to regulate the expression of LARP4. This research may provide some referential value to OC treatment.
Ras isoforms: signaling specificities in CD40 pathway
Authors: Nair Arathi , Chakraborty Sushmita , Banerji Late Anirban , Srivastava Ankita , Navare Charudutta , Saha Bhaskar
Published: January 2020

Background

Ras are small cellular GTPases which regulate diverse cellular processes. It has three isoforms: H-Ras, K-Ras, and N-Ras. Owing to the N-terminus (1–165 residues) sequence homology these isoforms were thought to be functionally redundant. However, only K-Ras-deficient mice but not H-Ras- and N-Ras-deficient mice show embryonic lethality. Similarly, mutations in a given Ras isoform are associated with a particular type of cancer. Moreover, we have previously reported that Ras isoforms perform unique functions inLeishmania majorinfection. Thus, Ras isoforms are implicated to have signaling and functional specificity but the mechanism remains to be elucidated.

Result

Using CD40 as a model receptor, we showed that depending on the strength of signaling, specific Ras isoforms are activated. Weak CD40 signal activates N-Ras, whereas strong signal activates H-Ras and K-Ras. Additionally, we showed that suppression of N-Ras expression reduced CD40-induced extracellular signal–regulated kinase-1/2 (ERK-1/2) activation and Interleukin (IL)-10 production; whereas suppression of H-Ras or K-Ras reduced CD40-induced p38 mitogen-activated protein kinase (p38MAPK) activation and IL-12 production. Furthermore, we showed that Ras isoforms have activator (GEF) specificity as weak CD40 signal-activated N-Ras requires Sos-1/2 whereas strong CD40 signal-activated H-Ras/K-Ras requires Ras-GRP as the guanine-nucleotide exchange factor (GEF) inducing ERK-1/2- or p38MAPK-mediated IL-10 or IL-12 productions, respectively, in macrophages. Silencing of syk reduced CD40-induced N-Ras activation but silencing of lyn inhibited H-Ras and K-Ras activation. In CD40 signaling, Ras isoforms also showed effector specificity; while H-Ras and K-Ras showed specificity for phosphatidyl inositol-3 kinase activation at high dose of CD40 stimulation, N-Ras primarily associated with Raf-1 at low dose of CD40 stimulation. Moreover, fractal analysis showed that functional site surface roughness for H-Ras (SurfaceFD = 2.39) and K-Ras (SurfaceFD = 2.39) are similar but significantly different from N-Ras (SurfaceFD = 2.25).

Conclusion

The activator and effector specificities of Ras isoforms in CD40 signaling indicated their differential involvement in CD40 pathway and in maintaining the reciprocity. Our observations reveal Ras-regulated signaling outcome and its potential for developing Ras isoform-targeted immunotherapy and prophylaxis.

Graphical abstract
Rapid diagnosis and comprehensive bacteria profiling of sepsis based on cell-free DNA
Authors: Chen Pei , Li Shuo , Li Wenyuan , Ren Jie , Sun Fengzhu , Liu Rui , Zhou Xianghong Jasmine
Published: January 2020

Background

Sepsis remains a major challenge in intensive care units, causing unacceptably high mortality rates due to the lack of rapid diagnostic tools with sufficient sensitivity. Therefore, there is an urgent need to replace time-consuming blood cultures with a new method. Ideally, such a method also provides comprehensive profiling of pathogenic bacteria to facilitate the treatment decision.

Methods

We developed a Random Forest with balanced subsampling to screen for pathogenic bacteria and diagnose sepsis based on cell-free DNA (cfDNA) sequencing data in a small blood sample. In addition, we constructed a bacterial co-occurrence network, based on a set of normal and sepsis samples, to infer unobserved bacteria.

Results

Based solely on cfDNA sequencing information from three independent datasets of sepsis, we distinguish sepsis from healthy samples with a satisfactory performance. This strategy also provides comprehensive bacteria profiling, permitting doctors to choose the best treatment strategy for a sepsis case.

Conclusions

The combination of sepsis identification and bacteria-inferring strategies is a success for noninvasive cfDNA-based diagnosis, which has the potential to greatly enhance efficiency in disease detection and provide a comprehensive understanding of pathogens. For comparison, where a culture-based analysis of pathogens takes up to 5 days and is effective for only a third to a half of patients, cfDNA sequencing can be completed in just 1 day and our method can identify the majority of pathogens in all patients.