bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a five-immune gene model as an independent prognostic factor in hepatocellular carcinoma
Authors: Chen Haitao , Li Yueying , Xiao Shu-Yuan , Guo Jianchun
Published: March 2021

Background

Hepatocellular carcinoma (HCC) is a common malignant tumor with a poor prognosis. We aimed to identify a new prognostic model of HCC based on differentially expressed (DE) immune genes.

Methods

The DE immune genes were identified based on an analysis of 374 cases of HCC and 50 adjacent non-tumor specimens from the Cancer Genome Atlas (TCGA) database. Univariate Cox analysis, Lasso regression, and multivariate Cox analysis were used to construct the model based on the training group. Survival analysis and the receiver operating characteristic (ROC) curves were used to evaluate model performance. The testing group and the entire group were subsequently used for validation of the model.

Results

A five-immune gene model consisted of HSPA4, ISG20L2, NDRG1, EGF, and IL17D was identified. Based on the model, the overall survival was significantly different between the high-risk and low-risk groups (P = 7.953e-06). The AUCs for the model at 1- and 3-year were 0.849 and 0.74, respectively. The reliability of the model was confirmed using the validation groups. The risk score was identified as an independent prognostic parameter and closely related to the content of immune cells from human HCC specimens.

Conclusion

We identified a five-immune gene model that can be used as an independent prognostic marker for HCC.
Temperament, physical activity and sedentary time in preschoolers – the DAGIS study
Authors: Leppänen Marja H. , Kaseva Kaisa , Pajulahti Riikka , Sääksjärvi Katri , Mäkynen Ella , Engberg Elina , Ray Carola , Erkkola Maijaliisa , Sajaniemi Nina , Roos Eva
Published: March 2021

Background

Identifying individual characteristics linked with physical activity (PA) and sedentary time (SED) can assist in designing health-enhancing interventions for children. We examined cross-sectional associations of temperament characteristics with 1) PA and SED and 2) meeting the PA recommendation in Finnish children.

Methods

Altogether, 697 children (age: 4.7 ± 0.9 years, 51.6% boys) within the Increased Health and Wellbeing in Preschools (DAGIS) study were included. Parents responded to the Very Short Form of the Children’s Behavior Questionnaire consisting of three temperament dimensions: surgency, negative affectivity, and effortful control. PA and SED were assessed for 7 days (24 h per day) using a hip-worn ActiGraph accelerometer, and the daily minutes spent in light PA (LPA), moderate PA (MPA), vigorous PA (VPA), and SED were calculated. The PA recommendation was defined as having PA at least 180 min/day, of which at least 60 min/day was in moderate-to-vigorous PA. Adjusted linear and logistic regression analyses were applied.

Results

Surgency was associated with LPA (B = 3.80,p = 0.004), MPA (B = 4.87,p < 0.001), VPA (B = 2.91,p < 0.001), SED (B = − 11.45,p < 0.001), and higher odds of meeting the PA recommendation (OR = 1.56,p < 0.001). Effortful control was associated with MPA (B = − 3.63,p < 0.001), VPA (B = − 2.50,p < 0.001), SED (B = 8.66,p < 0.001), and lower odds of meeting the PA recommendation (OR = 0.61,p = 0.004). Negative affectivity was not associated with PA, SED, or meeting the PA recommendation.

Conclusion

Children’s temperament should be considered when promoting PA in preschoolers. Special attention should be paid to children scoring high in the temperament dimension effortful control.
Associations between developmental timing of child abuse and conduct problem trajectories in a UK birth cohort
Authors: Bauer Andreas , Hammerton Gemma , Fraser Abigail , Fairchild Graeme , Halligan Sarah L.
Published: March 2021

Background

Although there is strong evidence for a relationship between child abuse and neglect and conduct problems, associations between child abuse experienced at different developmental stages and developmental trajectories of conduct problems have not been examined. We sought to investigate effects of timing of child abuse on conduct problem trajectories in a large UK birth cohort study.

Methods

We applied latent class growth analysis to identify conduct problem trajectories in the Avon Longitudinal Study of Parents and Children, using parent-rated conduct problems from ages 4–17 years (N = 10,648). Childhood-only and adolescence-only abuse, in addition to abuse in both developmental periods (‘persistent’ abuse), were assessed by retrospective self-report at age 22 years (N = 3172).

Results

We identified four developmental trajectories: early-onset persistent (4.8%), adolescence-onset (4.5%), childhood-limited (15.4%), and low (75.3%) conduct problems. Childhood-only abuse and ‘persistent’ abuse were associated with increased odds of being on the early-onset persistent and adolescence-onset conduct problem trajectories compared to the low conduct problems trajectory. Adolescence-only abuse was not predictive of trajectory membership. There were no associations between abuse and childhood-limited trajectory membership.

Conclusions

Early-onset persistent and adolescence-onset conduct problems showed similar patterns of association with abuse exposure, challenging developmental theories that propose qualitative, as opposed to quantitative, differences in environmental risk factors between these trajectories. The results also highlight that childhood-only and ‘persistent’ abuse were more strongly linked to elevated conduct problem trajectories than adolescence-only abuse, and that ‘persistent’ abuse is particularly detrimental.
Temporal patterns of suicide and circulatory system disease-related mortality are inversely correlated in several countries
Authors: Kaufman Marc J. , Fitzmaurice Garrett M.
Published: March 2021

Background

Nearly 800,000 suicides occur worldwide annually and suicide rates are increasing faster than population growth. Unfortunately, the pathophysiology of suicide remains poorly understood, which has hindered suicide prevention efforts. However, mechanistic clues may be found by studying effects of seasonality on suicide and other mortality causes. Suicides tend to peak in spring-summer periods and nadir in fall-winter periods while circulatory system disease-related mortality tends to exhibit the opposite temporal trends. This study aimed to determine for the first time whether monthly temporal cross-correlations exist between suicide and circulatory system disease-related mortality at the population level. If so and if common biological factors moderate risks for both mortality types, such factors may be discoverable and utilized to improve suicide prevention.

Methods

We conducted time series analyses of monthly mortality data from northern (England and Wales, South Korea, United States) and southern (Australia, Brazil) hemisphere countries during the period 2009–2018 (N = 41.8 million all-cause mortality cases). We used a Poisson regression variant of the standard cosinor model to determine peak months of mortality. We also estimated cross-correlations between monthly mortality counts from suicide and from circulatory system diseases.

Results

Suicide and circulatory disease-related mortality temporal patterns were negatively correlated in Australia (− 0.32), Brazil (− 0.57), South Korea (− 0.32), and in the United States (− 0.66), but no temporal correlation was discernable in England and Wales.

Conclusions

The negative temporal cross-correlations between these mortality types we found in 4 of 5 countries studied suggest that seasonal factors broadly and inversely moderate risks for circulatory disease-related mortality and suicide, but not in all regions, indicating that the effect is not uniform. Since the seasonal factors of temperature and light exert opposite effects on suicide and circulatory disease-related mortality in several countries, we propose that physiologically-adaptive circulatory system responses to heat and light may increase risk for suicide and should be studied to determine whether they affect suicide risk. For example, heat and light increase production and release of the bioactive gas nitric oxide and reduce circulatory system disease by relaxing blood vessel tone, while elevated nitric oxide levels are associated with suicidal behavior, inverse effects that parallel the inverse temporal mortality patterns we detected.
Exploring the mechanism through which a child-friendly storybook addresses barriers to child-participation during HIV care in primary healthcare settings in KwaZulu-Natal, South Africa
Authors: Mutambo Chipo , Shumba Kemist , Hlongwana Khumbulani W.
Published: March 2021

Background

Healthcare workers (HCWs) in South Africa widely use job-aids as practical tools to enhance the provision of HIV services, thereby improving patient-provider interactions during the care process. Job-aids are visual support materials that provide appropriate information using graphics and words in a simple and yet effective manner. We explored the mechanism through the KidzAlive Talk tool storybook (Talk tool), a child-centred job-aid for HCWs that facilitates child-participation during HIV consultations in primary healthcare (PHC) clinics implementing the KidzAlive model.

Methods

The study was conducted in PHC clinics across four districts; namely: uMkhanyakude, Zululand, uMgungundlovu, and eThekwini in KwaZulu-Natal (KZN), South Africa. We conducted in-depth interviews with children (n = 30), their primary caregivers (PCGs) (n = 30), and KidzAlive trained and mentored HCWs (n = 20). Data were collected in both English and isiZulu languages through user-specific, structured in-depth interviews. All the interviews were audio-recorded (with participants’ assent and consent, respectively). Data were transcribed verbatim, prior to translating the isiZulu transcripts to English. Translations were done by a member of the research team competent in both languages. Electronic data were imported to NVivo 10 for analysis and subsequently analysed using a thematic analysis method followed by a constant comparative and modified grounded theory analysis method.

Results

The findings identified the following barriers to child-participation: Primary caregiver limiting the child’s involvement due to fear of traumatising them; HCWs’ limited knowledge and skills to deliver child-centred HIV care; childhood developmental stage-related limitations and healthcare institutional paternalism. The Talk tool addresses the above barriers by using simple language and terminology to cater for children at various stages of development; alleviating HCWs’ and PCGs’ fear of possible psychological harm to the child; using storytelling and colourful cartoon illustrations for child edutainment; Being versatile by allowing for multiple utility and tackling institutional paternalism that limit child-involvement in the process of care.

Conclusions

This study provided evidence on how the Talk tool storybook addresses barriers to child-participation in the HIV care process. The evidence generated from this study is compelling enough to recommend the scale-up of this innovation in low-resource settings.
Low health literacy is associated with higher risk of type 2 diabetes: a cross-sectional study in Germany
Authors: Tajdar Daniel , Lühmann Dagmar , Fertmann Regina , Steinberg Tim , van den Bussche Hendrik , Scherer Martin , Schäfer Ingmar
Published: March 2021

Background

Low health literacy is believed to be associated with behaviours that increase the risk of type 2 diabetes. But there is limited knowledge on the relation between health literacy (HL) and diabetes risk, and whether improving HL could be a potential prevention strategy. Therefore, the main purpose of this study was to examine the link between HL and diabetes risk among non-diabetic adults.

Methods

We used data from the Hamburg Diabetes Prevention Survey, a population-based cross-sectional study in Germany. One thousand, two hundred and fifty-five non-diabetic subjects aged 18–60 years were eligible. The German Diabetes Risk Score (GDRS, ranging 0 to 123 points) was used to determine the individual risk of type 2 diabetes. The short version of the European Health Literacy Questionnaire (HLS-EU-Q16, ranging 0 to 16 points) was applied to assess the individual self-reported HL. Subjects were asked to self-estimate their diabetes risk, which was then compared with the calculated GDRS. Descriptive statistics were calculated to investigate group differences in the GDRS and self-estimated diabetes risk. Linear as well as logistic regression models were performed to analyse potential influencing variables of the GDRS as well as incorrect self-estimated diabetes risk. In three nested statistical models for each outcome, these analyses were adjusted for age, gender, educational level and the presence of chronic conditions.

Results

According to the criteria of the GDRS, 996 (79.4%) subjects showed “low risk”, 176 (14.0%) “still low risk”, 53 (4.2%) “elevated risk”, and 30 (2.4%) “high to very high risk” to develop type 2 diabetes within the next 5 years. In the statistical models including all control variables, subjects with “inadequate HL” scored 2.38 points higher on the GDRS (95% CI 0.378 to 4.336; P = 0.020) and had a 2.04 greater chance to estimate their diabetes risk incorrectly (OR 2.04; 95% CI 1.33 to 3.14; P = 0.001) compared to those with “sufficient HL”.

Conclusion

The risk of type 2 diabetes is increased in people with inadequate self-reported HL. People with high diabetes risk and inadequate HL might be provided with educational programs to improve diabetes knowledge and reduce behavioural risk factors.
The association between daily total physical activity and risk of cardiovascular disease among hypertensive patients: a 10-year prospective cohort study in China
Authors: Zhou Tingyu , Su Jian , Tao Ran , Qin Yu , Zhou Jinyi , Lu Yan , Hua Yujie , Jin Jianrong , Guo Yu , Chen Zhengming , Li Liming , Wu Ming
Published: March 2021

Background

The effect of high levels of physical activity and relationship between daily total physical activity and the risk of cardiovascular disease (CVD) among hypertensive people were not clear. This study aimed to explore the optimum level of physical activity for CVD prevention.

Methods

Data used in the present study was derived from the sub-study of China Kadoorie Biobank study (CKB) in Jiangsu province of China. The CKB was a prospective cohort study established during 2004–2008. At baseline, 53,259 participants aged 35–74 years were recruited for the CKB Jiangsu sub-study conducted in Wuzhong district of Suzhou City. Among those 53,259 participants, the 20,179 hypertensive individuals were our study population. The outcome events were cardiovascular diseases (CVDs), while the independent variable was total daily physical activity. The Cox proportional hazard models were introduced to investigate the association between total physical activity and CVDs, reporting as hazard ratios (HR) and 95% confidence intervals (CIs).

Results

During a 10.1-year follow-up, 2419 CVD cases were identified. After adjustment for potential confounding factors, compared with participants at the lowest level of daily total physical activity, the hazard ratios for CVDs were 0.87 (95%CI: 0.79–0.97), 0.73 (95%CI: 0.65–0.83) and 0.75 (95%CI: 0.65–0.85) for participants within 2, 3 and 4 quartiles of physical activity. Such a negative association between total physical activity and CVDs were also observed among participants by gender and age-group, but within patients with stage 1 hypertension only. Moreover, the association of physical activity with CVDs was U-shape and the lowest HR (0.63, 95%CI: 0.54–0.74) was observed at 35.4 MET-h/d of total physical activity.

Conclusions

Total daily physical activity was negatively associated with CVDs among hypertensive adults in China, and this association was U-shape. It has some public health implications that community-based total physical activity intervention campaigns can be of help for CVDs prevention among hypertensive people in China.
Role for colorectal teams to support non-colorectal teams to improve clinical outcomes and adherence to ERAS guidelines for segmental colectomy: a cohort study
Authors:   Trainee Intern Research Group, Mallard Simonette R. , Clifford Kari A. , Park R. , Cousins Kim , Patton Ann , Woodfield John C. , Thompson-Fawcett Mark
Published: March 2021

Background

To identify whether compliance with Enhanced Recovery After Surgery (ERAS) Society recommendations is associated with length of stay (LOS) in a New Zealand hospital for patients undergoing segmental colectomy in mixed acute and elective general surgery wards.

Methods

Consecutive elective colorectal surgeries (n = 770) between October 2012 and February 2019 were audited. Patients with non-segmental colectomies, multi-organ surgeries, LOS > 14 days, and those who died were excluded. Logistic regression was used to determine the relationship between patient demographics, compliance with ERAS guidelines, and suboptimal LOS (> 4 days).

Results

Analysis included 376 patients. Age, surgery prior to 2014, surgical approach, non-colorectal surgical team, operation type, and complications were significantly associated with suboptimal LOS. Non-compliance with ERAS recommendations for laparoscopy [OR 8.9, 95% CI (4.52, 19.67)], removal of indwelling catheters (IDC) [OR 3.14, 95% CI (1.85, 5.51)], use of abdominal drains [OR 4.27, 95% CI (0.99, 18.35)], and removal of PCA [OR 8.71, 95% CI (1.78, 157.27)], were associated with suboptimal LOS (univariable analysis). Multivariable analysis showed that age, surgical team, late removal of IDC, and open approach were independent predictors of suboptimal LOS.

Conclusions

Non-compliance with ERAS guidelines for laparoscopic approach and early removal of IDC was higher among procedures performed by non-colorectal surgery teams, and was also associated with adverse postoperative events and suboptimal LOS. This study demonstrates the importance of the surgical team’s expertise in affecting surgical outcomes, and did not find significant independent associations between most individual ERAS guidelines and suboptimal LOS once adjusting for other factors.
Comparison of prevalence of diabetes complications in Brazilian and Mexican adults: a cross-sectional study
Authors: Martins Renata Breda , Ordaz-Briseño Sandra Azucena , Flores-Hernández Sarahí , Bós Ângelo José Gonçalves , Baptista-Rosas Raúl C. , Mercado-Sesma Arieh Roldán
Published: March 2021

Background

Type 2 diabetes is more frequent in Latin American people than in non-Hispanic whites due to a combination of genetic and lifestyle risk factors. Brazil and Mexico are the most populous countries in Latin America. The present study aimed to compare the results of the National Health Survey “PNS” in Brazil and the National Survey Health and Nutrition “ENSANUT” in Mexico regarding the prevalence, complications and healthcare issues of diabetes in both countries.

Methods

A cross-sectional study was conducted with data from the National Health Survey (PNS) of 2013 in Brazil and the National Survey of Health and Nutrition (ENSANUT) of 2018 in Mexico. The prevalence of diabetes, complications and risk factors related to developing diabetes were considered.

Results

The respondents included 3636 individuals in Brazil and 4555 individuals in Mexico. There were significant differences in age and time living with diabetes between the two countries. Mexican people had twice as likely as Brazilian people to have a complication (p < 0.0001). The principal risk factor (OR 2.47; p ≤ 0.0001) for developing any diabetic complication was living with diabetes for more than 15 years. Visual impairment was the most frequent complication in both countries, but it was more prevalent in Mexico (p ≤ 0.001).

Conclusions

Diabetes complications are important health problems in Brazil and Mexico. Visual impairment was the principal complication in both countries. Several factors, such as access to and type of health system, living in a rural area, treatment, BMI and performing preventive actions, affected the risk of developing a complication. However, living with diabetes for more than 15 years was the principal risk factor. National health surveys have added significant information on the impact of diabetes in these Latin American populations. This comparison of data could provide valuable information to guide national policies and program decisions in both countries.
Importance of support groups to the health and well-being of vulnerable children and young people living with HIV: a case study of the Kids Clubs program in Haiti
Authors: Settergren Susan K. , Philippe Robert , St. Louis Joanne , Segaren Nathaniel , Boisson Sylvie , Lewis Tessa , Désinor Olbeg , François Kesner
Published: March 2021

Background

Although access to antiretroviral therapy (ART) among children and young people living with HIV has increased in recent years, adherence to medication and viral suppression remain challenges. Evidence of benefits of support groups is growing and reflects a range of models and approaches. Since 2014, hospital-linked psychosocial support groups for children and young people living with HIV, known as Kids Clubs, have been established throughout Haiti. The program provides safe spaces for them to meet with peers, supports medication adherence, delivers health and life skills education, and facilitates linkages with clinic visits and social services. This study describes program enrollment and participant engagement, ART adherence and viral suppression among participants, and other outcomes attributed to the program by participants, caregivers, and program implementers.

Methods

Our mixed methods study included quantitative analysis of program monitoring data on rollout and attendance, and medication adherence and viral load results extracted from medical records. We collected qualitative data from club members, caregivers, and implementers about their experiences with the clubs and the impact of participation.

Results

From January 2014–December 2018, 1330 individuals aged 8–29 were enrolled in the program; over three-quarters participated for at least 12 months. In 2018, 1038 members attended at least one club meeting; more than half missed three or fewer monthly meetings. Three-quarters of ever-enrolled members reported consistent medication use at their most recent clinic visit; 64.2% (600/935) of those with a recent viral load test were virally suppressed. Level of club attendance was positively associated with ART adherence (p < 0.01) and viral suppression (p < 0.05). Club members, caregivers, and implementers noted the value of the clubs to participants’ retention in care and medication adherence, health knowledge, and capacity to deal with peer pressure, stigma, shyness, and depression.

Conclusions

The Kids Club program has been successful in scaling HIV support services to highly vulnerable children and young people through peer-based groups, and program participation has led to a range of benefits. Efforts to innovate, evaluate, and scale support strategies for vulnerable young populations must be accelerated in order to ensure that they survive, thrive, and reach their full potential.
Correction to: Quality assessment with diverse studies (QuADS): an appraisal tool for methodological and reporting quality in systematic reviews of mixed- or multimethod studies
Authors: Harrison Reema , Jones Benjamin , Gardner Peter , Lawton Rebecca
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
Relationship between diet quality scores and the risk of frailty and mortality in adults across a wide age spectrum
Authors: Jayanama Kulapong , Theou Olga , Godin Judith , Cahill Leah , Shivappa Nitin , Hébert James R. , Wirth Michael D. , Park Yong-Moon , Fung Teresa T. , Rockwood Kenneth
Published: March 2021

Background

Beyond intakes of total energy and individual nutrient, eating patterns may influence health, and thereby the risk of adverse outcomes. How different diet measures relate to frailty—a general measure of increased vulnerability to unfavorable health outcomes—and mortality risk, and how this might vary across the life course, is not known. We investigated the associations of five dietary indices (Nutrition Index (NI), the energy-density Dietary Inflammatory Index (E-DII™), Healthy Eating Index-2015 (HEI-2015), Mediterranean Diet Score (MDS), and Dietary Approaches to Stop Hypertension (DASH)) with frailty and mortality.

Methods

We included 15,249 participants aged ≥ 20 years from the 2007–2012 cohorts of the National Health and Nutrition Examination Survey (NHANES).The NI combined 31 nutrition-related deficits. The E-DII is a literature-derived dietary index associated with inflammation. The HEI-2015 assesses adherence to the Dietary Guidelines of Americans. The MDS represents adherence to the traditional Mediterranean diet. DASH combines macronutrients and micronutrients to prevent hypertension. Frailty was evaluated using a 36-item frailty index. Mortality status was ascertained up to December 31, 2015.

Results

Participants’ mean age was 47.2 ± 16.7 years and 51.7% were women. After adjusting for age, sex, race, educational level, marital and employment status, smoking, BMI, and study cohort, higher NI and E-DII scores and lower HEI-2015, MDS, and DASH scores were individually significantly associated with frailty. All dietary scores were significantly associated with 8-year mortality risk after adjusting for basic covariates and frailty: NI (hazard ratio per 0.1 point, 1.15, 95%CI 1.10–1.21), E-DII (per 1 point, 1.05, 1.01–1.08), HEI-2015 (per 10 points, 0.93, 0.89–0.97), MDS (per 1 point, 0.94, 0.90–0.97), and DASH (per 1 point, 0.96, 0.93–0.99). The associations of E-DII, HEI-2015, and MDS scores with 8-year mortality risk persisted after additionally adjusting for NI.

Conclusions

NI, E-DII, HEI-2015, MDS, and DASH scores are associated with frailty and 8-year mortality risk in adults across all ages. Nevertheless, their mechanisms and sensitivity to predict health outcomes may differ. Nutrition scores have the potential to include measures of both consumption and laboratory and physical measures of exposure.
Analysis of risk allele frequencies of single nucleotide polymorphisms related to open-angle glaucoma in different ethnic groups
Authors: Shin Hyun-Tae , Yoon Byung Woo , Seo Je Hyun
Published: March 2021

Background

The prevalence of open-angle glaucoma (OAG) varies from 0.5% to 7.0% among populations of diverse ancestry, suggesting the existence of genetic differences. The purposes of this study were to provide insights into genetic causes of OAG, which can result in prevalence and phenotype differences among populations of diverse ancestry for OAG, and to compare allele frequencies of intraocular pressure (IOP) elevation-related SNPs in OAG among Koreans and other ethnic groups.

Methods

We collected the data on a total of 135 OAG-associated single nucleotide polymorphisms (SNPs) from a genome-wide association studies (GWAS) catalog. The population-level allele frequencies of these SNPs were derived based on the 1000 Genomes Project and Korean Reference Genome Database. We used Fisher's exact test to assess whether the effect allele at a given SNP was significantly enriched or depleted.

Results

European, American, and South Asian populations showed similar heatmap patterns, while African, East Asian, and Korean populations had distinct patterns. Korean population presented different profiles compared to other groups; rs1579050 (FMNL2 gene), rs2024211 (CAV2;CAV1), and rs8141433 (GNB1L;TXNRD2 gene), which are known to be associated with IOP variation, were enriched in Americans, Europeans, and Africans, and depleted in Koreans. These can be the candidates for the causative genes of differences in the prevalence of IOP variation in OAG according to ethnic groups.

Conclusions

Differences in allele frequencies associated with IOP related SNPs between Koreans and other ethnicities were observed, which may explain the high prevalence of OAG with normal IOP predominantly in Koreans and East Asians.
CDC42EP3 promotes colorectal cancer through regulating cell proliferation, cell apoptosis and cell migration
Authors: Feng Qiang , Xu Dongkui , Zhou Mingyao , Wu Zijian , Wu Zhiyuan , Wang Zheng , Bi Jianjun , Pei Wei
Published: March 2021

Background

Nowadays, colorectal cancer (CRC) is one of the most commonly diagnosed malignant tumors worldwide, the incidence rate of which is still increasing year by year. Herein, the objective of this study is to investigate whether CDC42EP3 has regulatory effects in CRC.

Methods

First, CDC42EP3 knockdown cell model based on HCT116 and RKO cell lines was successfully constructed, which was further used for constructing mouse xenotransplantation models. Importantly, effects of CDC42EP3 knockdown on proliferation, colony formation, apoptosis, and migration of CRC were accessed by MTT assay, EdU staining assay, colony formation assay, Flow cytometry, and Transwell assay.

Results

As the results, we showed that CDC42EP3 was significantly upregulated in CRC, and its high expression was associated with tumor progression. Furthermore, knockdown of CDC42EP3 could inhibit proliferation, colony formation and migration, and promote apoptosis of CRC cells in vitro. In vivo results further confirmed knockdown of CDC42EP3 attenuated tumor growth in CRC. Interestingly, the regulation of CRC by CDC42EP3 involved not only the change of a variety of apoptosis-related proteins, but also the regulation of downstream signaling pathway.

Conclusion

In conclusion, the role of CDC42EP3 in CRC was clarified and showed its potential as a target of innovative therapeutic approaches for CRC.
Lifetime and past-month substance use and injection among street-based female sex workers in Iran
Authors: Roshanfekr Payam , Khezri Mehrdad , Karimi Salah Eddin , Vameghi Meroe , Ali Delaram , Ahmadi Sina , Ahounbar Elahe , Mahzari Kambiz , Roshanpajouh Mohsen , Noroozi Mehdi , Shokoohi Mostafa , Mirzazadeh Ali
Published: March 2021

Background

Street-based female sex workers (FSWs) are highly at risk of HIV and other harms associated with sex work. We assessed the prevalence of non-injection and injection drug use and their associated factors among street-based FSWs in Iran.

Methods

We recruited 898 FSWs from 414 venues across 19 major cities in Iran between October 2016 and March 2017. Correlates of lifetime and past-month non-injection and injection drug use were assessed through multivariable logistic regression models. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were reported.

Results

Lifetime and past-month non-injection drug use were reported by 60.3% (95% CI 51, 84) and 47.2% (95% CI 38, 67) of FSWs, respectively. The prevalence of lifetime and past-month injection drug use were 8.6% (95% CI 6.9, 10.7) and 3.7% (95% CI 2.6, 5.2), respectively. Recent non-injection drug use was associated with divorced marital status (AOR 2.00, 95% CI 1.07, 3.74), temporary marriage (AOR 4.31 [1.79, 10.40]), had > 30 clients per month (AOR 2.76 [1.29, 5.90]), ever alcohol use (AOR 3.03 [1.92, 6.79]), and history of incarceration (AOR 7.65 [3.89, 15.30]). Similarly, lifetime injection drug use was associated with ever alcohol use (AOR 2.74 [1.20–6.20]), ever incarceration (AOR 5.06 [2.48–10.28]), and ever group sex (AOR 2.44 [1.21–4.92]).

Conclusions

Non-injection and injection drug use are prevalent among street-based FSWs in Iran. Further prevention programs are needed to address and reduce harms associated with drug use among this vulnerable population in Iran.
Does cellular senescence play an important role in the prognosis of sarcomatoid carcinoma of the pancreas?
Authors: Kimura Toshihisa , Togawa Tamotsu , Iida Atsushi , Noriki Sakon , Sato Yasunori , Goi Takanori
Published: March 2021

Aim

Sarcomatoid carcinoma of the pancreas (SCP) is an extremely rare and aggressive disease with poor prognosis. We have already reported a rare case of SCP with long-term survival. In the present article, we investigate the underlying mechanisms of patient’s long-term survival from the point of view of cellular senescence which was examined in three SCP cases, including our reported case, using immunohistochemical analysis.

Findings

The expressions of cellular senescence marker were observed in the sarcomatous component of the patient with long-term survival but not observed in the other patients with short- term survival. Thus, we can speculate that cellular senescence might play an important role in the reduction of the cell proliferative and metastatic activities of sarcomatous cells, leading to long-term patient survival.
Combined primary hepatic neuroendocrine carcinoma and hepatocellular carcinoma: case report and literature review
Authors: Nakano Akira , Hirabayashi Kenichi , Yamamuro Hiroshi , Mashiko Taro , Masuoka Yoshihito , Yamamoto Seiichiro , Ozawa Soji , Nakagohri Toshio
Published: March 2021

Background

Hepatocellular carcinoma (HCC) can grow in a mosaic pattern, often combined with various non-hepatocellular cells. However, HCC combined with a neuroendocrine carcinoma (NEC) component is rarely reported, and its clinical features, origin, diagnosis, and behavior have not been established. In the literature, mixed HCC–NEC tumors are categorized as either collision type or combined type, depending on their microscopic features. Here, we report a patient with a combined-type HCC–NEC tumor.

Case presentation

An asymptomatic 84-year-old woman was found to have a solid mass in the right lobe of the liver. Laboratory and radiologic examinations showed typical findings of HCC, including arterial-phase enhancement, and portal- and delay-phase washout. She was treated by partial laparoscopic hepatectomy of segment 5. Pathological examination showed that the tumor was predominantly HCC, partly admixed with an NEC component. A transitional zone between the HCC and NEC tissues was also observed. The tumor was finally diagnosed as a combined-type primary mixed NEC–HCC tumor. After the preoperative diagnosis, the patient underwent somatostatin receptor scintigraphy to detect the primary NEC lesion, but no accumulation was found in any other part of her body. She has been free of recurrence for 9 months since the surgery.

Conclusion

Mixed HCC–NEC tumors are extremely rare, and correct diagnosis requires multidisciplinary collaboration. The accumulation of further cases is needed to help understand the exact pathology, diagnosis, and treatment of this disease.
Viscoelastometry for detecting oral anticoagulants
Authors: Groene Philipp , Wagner Daniela , Kammerer Tobias , Kellert Lars , Giebl Andreas , Massberg Steffen , Schäfer Simon Thomas
Published: March 2021

Background

Determination of anticoagulant therapy is of pronounced interest in emergency situations. However, routine tests do not provide sufficient insight. This study was performed to investigate the impact of anticoagulants on the results of viscoelastometric assays using the ClotPro device.

Methods

This prospective, observational study was conducted in patients receiving dabigatran, factor Xa (FXa)-inhibitors, phenprocoumon, low molecular weight heparin (LMWH) or unfractionated heparin (UFH) (local ethics committee approval number: 17–525-4). Healthy volunteers served as controls. Viscoelastometric assays were performed, including the extrinsic test (EX-test), intrinsic test (IN-test) Russel’s viper venom test (RVV-test), ecarin test (ECA-test), and the tissue plasminogen activator test (TPA-test).

Results

70 patients and 10 healthy volunteers were recruited. Clotting time in the EX-test (CTEX-test) was significantly prolonged versus controls by dabigatran, FXa inhibitors and phenprocoumon. CTIN-test was prolonged by dabigatran, FXa inhibitors and UFH. Dabigatran, FXa inhibitors and UFH significantly prolonged CTRVV-test in comparison with controls (median 200, 207 and 289 vs 63 s, respectively; all p < 0.0005). Only dabigatran elicited a significant increase in CTECA-test compared to controls (median 307 vs 73 s; p < 0.0001). CTECA-test correlated strongly with dabigatran plasma concentration (measured by anti-IIa activity; r = 0.9970; p < 0.0001) and provided 100% sensitivity and 100% specificity for detecting dabigatran. Plasma concentrations (anti-XA activity) of FXa inhibitors correlated with CTRVV-test (r = 0.7998; p < 0.0001), and CTRVV-test provided 83% sensitivity and 64% specificity for detecting FXa inhibitors.

Conclusions

In emergency situations, ClotPro viscoelastometric assessment of whole-blood samples may help towards determining the presence and type of anticoagulant class that a patient is taking.

Trial registration

German clinical trials database ID: DRKS00015302.
Novel and recurrent BRCA1/BRCA2 germline mutations in patients with breast/ovarian cancer: a series from the south of Tunisia
Authors: Ben Ayed-Guerfali Dorra , Ben Kridis-Rejab Wala , Ammous-Boukhris Nihel , Ayadi Wajdi , Charfi Slim , Khanfir Afef , Sellami-Boudawara Tahia , Frikha Mounir , Daoud Jamel , Mokdad-Gargouri Raja
Published: March 2021

Background

The incidence of breast cancer (BC) and/or ovarian cancer (OC) is increasing in Tunisia especially in young women and mostly those with family history. However, the spectrum ofBRCAmutations remains little explored in Tunisian patients in particular in the southern region.

Methods

We sequenced the entire coding regions ofBRCA1andBRCA2genes using next generation sequencing (NGS) in 134 selected patients with BC and/or OC.

Results

Among the 134 patients, 19 (14.17%) carried pathogenic mutations (10 areBRCA1mutation carriers and 9 areBRCA2mutation carriers) that are mainly frameshift index (76.9%). Interestingly, 5 out of the 13 variants (38.46%) were found at least twice in unrelated patients, as the c.1310-1313 delAAGA inBRCA2and the c.5030_5033 delCTAA that has been identified in 4/98 BC patients and in 3/15 OC patients from unrelated families with strong history of cancer. Besides recurrent mutations, 6 variant (4 inBRCA1and 2 inBRCA2) were not reported previously. Furthermore, 3 unrelated patients carried the VUS c.9976A > T, (K3326*) inBRCA2exon 27.BRCAcarriers correlated significantly with tumor site (p = 0.029) and TNBC cases (p = 0.008). In the groups of patients aged between 31 and 40, and 41–50 years,BRCA1mutations occurred more frequently in patients with OC than those with BC, and converselyBRCA2carriers are mostly affected with BC (p = 0.001, and p = 0.044 respectively).

Conclusions

The overall frequency of the BRCA germline mutations was 14.17% in patients with high risk of breast/ovarian cancer. We identified recurrent mutations as the c.1310_1313 delAAGA inBRCA2gene and the c.5030_5033 delCTAA inBRCA1gene that were found in 4% and 20% of familial BC and OC respectively. Our data will contribute in the implementation of genetic counseling and testing for families with high-risk of BC and/or OC.
Correction to: The DNA methylation of FOXO3 and TP53 as a blood biomarker of late-onset asthma
Authors: Yuan Lin , Wang Leyuan , Du Xizi , Qin Ling , Yang Ming , Zhou Kai , Wu Mengping , Yang Yu , Zheng Zhiyuan , Xiang Yang , Qu Xiangping , Liu Huijun , Qin Xiaoqun , Liu Chi
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
The influence of powered prostheses on user perspectives, metabolics, and activity: a randomized crossover trial
Authors: Kim Jay , Wensman Jeffrey , Colabianchi Natalie , Gates Deanna H.
Published: March 2021

Background

Powered prosthetic ankles provide battery-powered mechanical push-off, with the aim of reducing the metabolic demands of walking for people with transtibial amputations. The efficacy of powered ankles has been shown in active, high functioning individuals with transtibial amputation, but is less clear in other populations. Additionally, it is unclear how use of a powered prosthesis influences everyday physical activity and mobility.

Methods

Individuals with unilateral transtibial amputations participated in a randomized clinical trial comparing their prescribed, unpowered prosthesis and the BiOM powered prosthesis. Participants’ metabolic costs and self-selected walking speeds were measured in the laboratory and daily step count, daily steps away from home, and walking speed were measured over two weeks of at-home prosthesis use. Participants also rated their perception of mobility and quality of life and provided free-form feedback. Dependent measures were compared between prostheses and the relationships between metabolic cost, perception of mobility, and characteristics of walking in daily life were explored using Pearson’s correlations.

Results

Twelve people were randomly allocated to the powered prosthesis first (n = 7) or unpowered prosthesis first (n = 5) and ten completed the full study. There were no differences in metabolic costs (p = 0.585), daily step count (p = 0.995), walking speed in-lab (p = 0.145) and in daily life (p = 0.226), or perception of mobility between prostheses (p ≥ 0.058). Changes varied across participants, however. There were several medium-sized effects for device comparisons. With the powered prosthesis, participants had increased self-reported ambulation (g = 0.682) and decreased frustration (g = 0.506).

Conclusions

There were no universal benefits of the powered prosthesis on function in the lab or home environment. However, the effects were subject-specific, with some reporting preference for power and improved mobility, and some increasing their activity and decreasing their metabolic effort. Additionally, self-reported preferences did not often correlate with objective measures of function. This highlights the need for future clinical research to include both perception and objective measures to better inform prosthetic prescription.

Trial registration: https://clinicaltrials.gov, #NCT02828982.
Registered 12 July 2016, https://clinicaltrials.gov/ct2/show/NCT02828982
Correction to: Incentivizing appropriate malaria case management in the private sector: a study protocol for two linked cluster randomized controlled trials to evaluate provider- and client-focused interventions in western Kenya and Lagos, Nigeria
Authors: Woolsey Aaron M. , Simmons Ryan A. , Woldeghebriel Meley , Zhou Yunji , Ogunsola Oluwatosin , Laing Sarah , Olaleye Tayo , Kipkoech Joseph , Rojas Bomar Mendez , Saran Indrani , Odhiambo Mercy , Malinga Josephine , Ambani George , Kimachas Emmah , Fashanu Chizoba , Wiwa Owens , Menya Diana , Laktabai Jeremiah , Visser Theodoor , Turner Elizabeth L. , O’Meara Wendy Prudhomme
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
Identification of key genes in hepatitis B associated hepatocellular carcinoma based on WGCNA
Authors: Liu Chang , Dai Qinghai , Ding Qian , Wei Min , Kong Xiaohong
Published: March 2021

Chronic Infection of Hepatitis B virus (HBV) is one risk factor of hepatocellular carcinoma (HCC). Much effort has been made to research the process of HBV-associated HCC, but its molecular mechanisms of carcinogenesis remain vague. Here, weighted gene co-expression network analysis (WGCNA) was employed to explore the co-expressed modules and hub/key genes correlated to HBV-associated HCC. We found that genes of the most significant module related to HBV-associated HCC were enriched in DNA replication, p53 signaling pathway, cell cycle, and HTLV-1 infection associated pathway; these cellular pathways played critical roles in the initiation and development of HCC or viral infections. Furthermore, seven hub/key genes were identified based on the topological network analysis, and their roles in HCC were verified by expression and Kaplan-Meier survival analysis. Protein-protein interaction and KEGG pathway analysis suggested that these key genes may stimulate cellular proliferation to promote the HCC progression. This study provides new perspectives to the knowledge of the key pathways and genes in the carcinogenesis process of HBV-associated HCC, and our findings provided potential therapeutic targets and clues of the carcinogenesis of HBV-associated HCC.
RASMA: a reverse search algorithm for mining maximal frequent subgraphs
Authors: Salem Saeed , Alokshiya Mohammed , Hasan Mohammad Al
Published: March 2021

Background

Given a collection of coexpression networks over a set of genes, identifying subnetworks that appear frequently is an important research problem known as mining frequent subgraphs. Maximal frequent subgraphs are a representative set of frequent subgraphs; A frequent subgraph is maximal if it does not have a super-graph that is frequent. In the bioinformatics discipline, methodologies for mining frequent and/or maximal frequent subgraphs can be used to discover interesting network motifs that elucidate complex interactions among genes, reflected through the edges of the frequent subnetworks. Further study of frequent coexpression subnetworks enhances the discovery of biological modules and biological signatures for gene expression and disease classification.

Results

We propose a reverse search algorithm, called RASMA, for mining frequent and maximal frequent subgraphs in a given collection of graphs. A key innovation in RASMA is a connected subgraph enumerator that uses a reverse-search strategy to enumerate connected subgraphs of an undirected graph. Using this enumeration strategy, RASMA obtains all maximal frequent subgraphs very efficiently. To overcome the computationally prohibitive task of enumerating all frequent subgraphs while mining for the maximal frequent subgraphs, RASMA employs several pruning strategies that substantially improve its overall runtime performance. Experimental results show that on large gene coexpression networks, the proposed algorithm efficiently mines biologically relevant maximal frequent subgraphs.

Conclusion

Extracting recurrent gene coexpression subnetworks from multiple gene expression experiments enables the discovery of functional modules and subnetwork biomarkers. We have proposed a reverse search algorithm for mining maximal frequent subnetworks. Enrichment analysis of the extracted maximal frequent subnetworks reveals that subnetworks that are frequent are highly enriched with known biological ontologies.
Caveolin-1 deficiency impairs synaptic transmission in hippocampal neurons
Authors: Koh Soulmee , Lee Wongyoung , Park Sang Myun , Kim Sung Hyun
Published: March 2021

In addition to providing structural support, caveolin-1 (Cav1), a component of lipid rafts, including caveolae, in the plasma membrane, is involved in various cellular mechanisms, including signal transduction. Although pre-synaptic membrane dynamics and trafficking are essential cellular processes during synaptic vesicle exocytosis/synaptic transmission and synaptic vesicle endocytosis/synaptic retrieval, little is known about the involvement of Cav1 in synaptic vesicle dynamics. Here we demonstrate that synaptic vesicle exocytosis is significantly impaired in Cav1–knockdown (Cav1–KD) neurons. Specifically, the size of the synaptic recycled vesicle pool is modestly decreased in Cav1–KD synapses and the kinetics of synaptic vesicle endocytosis are somewhat slowed. Notably, neurons rescued by triple mutants of Cav1 lacking palmitoylation sites mutants show impairments in both synaptic transmission and retrieval. Collectively, our findings implicate Cav1 in activity-driven synaptic vesicle dynamics—both exocytosis and endocytosis—and demonstrate that palmitoylation of Cav1 is important for this activity.