bluuebunny/crossref_metadata_2025 huggingface dataset:
WDHD1 facilitates G1 checkpoint abrogation in HPV E7 expressing cells by modulating GCN5
Authors: Zhou Yunying , Pei Fengyan , Ji Mingyu , Zhang Fang , Sun Yingshuo , Zhao Qianqian , Wang Xiao , Hong Yatian , Tian Juanjuan , Wang Yunshan , Chen Jason J.
Published: September 2020

Background

Genomic instability is a hallmark of cancer. The G1 checkpoint allows cells to repair damaged DNA that may lead to genomic instability. The high-risk human papillomavirus (HPV) E7 gene can abrogate the G1 checkpoint, yet the mechanism is still not fully understood. Our recent study showed that WDHD1 (WD repeat and high mobility group [HMG]-box DNA-binding protein 1) plays a role in regulating G1 checkpoint of E7 expressing cells. In this study, we explored the mechanism by which WDHD1 regulates G1 checkpoint in HPV E7 expressing cells.

Methods

NIKS and RPE1 derived cell lines were used. Real-time PCR, Rescue experiment, FACS and BrdU labeling experiments were performed to examine role of GCN5 in G1 checkpoint abrogation in HPV-16 E7 expressing cells.

Results

In this study, we observed that WDHD1 facilitates G1 checkpoint abrogation by modulating GCN5 in HPV E7 expressing cells. Notably, depletion of WDHD1 caused G1 arrest while overexpression of GCN5 rescued the inhibitory effects of WDHD1 knockdown on G1/S progression. Furthermore, siWDHD1 significantly decreased cell cycle proliferation and DNA synthesis that was correlated with Akt phosphorylation (p-Akt), which was reversed by GCN5 overexpression in HPV E7 expressing cells.

Conclusions

In summary, our data identified a WDHD1/GCN5/Akt pathway leading to the abrogation of G1 checkpoint in the presence of damaged DNA, which may cause genomic instability and eventually HPV induced tumorigenesis.
LINC00649 underexpression is an adverse prognostic marker in acute myeloid leukemia
Authors: Guo Chao , Gao Ya-yue , Ju Qian-qian , Zhang Chun-xia , Gong Ming , Li Zhen-ling
Published: September 2020

Background

Long noncoding RNAs (lncRNA) play a role in leukemogenesis, maintenance, development, and therapeutic resistance of AML. While few studies have focused on the prognostic significance of LINC00649 in AML, which we aim to investigate in this present study.

Methods

We compared the expression level of LINC00649 between AML patients and healthy controls. The Kaplan-Meier curves of AML patients expressing high versus low level of LINC00649 was performed. The LINC00649 correlated genes/miRNAs/lncRNAs and methylation CpG sites were screened by Pearson correlation analysis with R (version 3.6.0), using TCGA-LAML database. The LINC00649 associated ceRNA network was established using lncBase 2.0 and miRWalk 2.0 online tools, combining results from correlation analysis. Finally, a prediction model was constructed using LASSO-Cox regression.

Results

LINC00649 was underexpressed in bone marrow of AML group than that in healthy control group. The patients of LINC00649-low group have significantly inferior PFS and OS. A total of 154 mRNAs, 31 miRNAs, 28 lncRNAs and 1590 methylated CpG sites were identified to be significantly correlated with LINC00649. Furthermore, the network of ceRNA was established with 6 miRNAs and 122 mRNAs. The Lasso-Cox model fitted OS/PFS to novel prediction models, which integrated clinical factors, ELN risk stratification, mRNA/miRNA expression and methylation profiles. The analysis of time-dependent ROC for our model showed a superior AUC (AUC = 0.916 at 1 year, AUC = 0.916 at 3 years, and AUC = 0.891 at 5 years).

Conclusions

Low expression of LINC00649 is a potential unfavorable prognostic marker for AML patients, which requires the further validation. The analysis by LASSO-COX regression identified a novel comprehensive model with a superior diagnostic utility, which integrated clinical and genetic variables.
Cell-in-cell phenomenon associates with aggressive characteristics and cancer-related mortality in early oral tongue cancer
Authors: Almangush Alhadi , Mäkitie Antti A. , Hagström Jaana , Haglund Caj , Kowalski Luiz Paulo , Nieminen Pentti , Coletta Ricardo D. , Salo Tuula , Leivo Ilmo
Published: September 2020

Background

Cell-in-cell structures (caused by cell cannibalistic activity) have been related to prognosis of many cancers. This is the first multi-institutional study to assess the prognostic impact of cell-in-cell structures in a large cohort of early oral tongue squamous cell carcinomas (OTSCC).

Methods

A total of 308 cases from five Finnish University Hospitals and from the A.C. Camargo Cancer Center, São Paulo, Brazil, were included in this study. Cell-in-cell structures were evaluated on surgical postoperative sections that stained with hematoxylin and eosin staining.

Results

We found that cell-in-cell structures associated with cancer-related mortality in univariable analysis with a hazard ratio (HR) of 2.99 (95%CI 1.52–5.88; P = 0.001). This association was confirmed in multivariable analysis (HR 2.22, 95%CI 1.12–4.44; P = 0.024). In addition, statistically significant associations were observed between the cell-in-cell structures and other adverse histopathologic characteristics including deep invasion (P <  0.001), high index of tumor budding (P = 0.007), worst pattern of invasion (P <  0.001), perineural invasion (P = 0.01), and stroma-rich pattern (P = 0.001).

Conclusions

Our findings demonstrate a significant relationship between cell-in-cell formation and aggressive characteristics of early OTSCC. Cell-in-cell structures have a distinct impact as a novel prognostic indicator in early OTSCC and they can be easily assessed during routine pathology practice.
Patient and physician factors associated with Oncotype DX and adjuvant chemotherapy utilization for breast cancer patients in New Hampshire, 2010–2016
Authors: Schwedhelm Thomas M. , Rees Judy R. , Onega Tracy , Zipkin Ronnie J. , Schaefer Andrew , Celaya Maria O. , Moen Erika L.
Published: September 2020

Background

Oncotype DX® (ODX) is used to assess risk of disease recurrence in hormone receptor positive, HER2-negative breast cancer and to guide decisions regarding adjuvant chemotherapy. Little is known about how physician factors impact treatment decisions. The purpose of this study was to examine patient and physician factors associated with ODX testing and adjuvant chemotherapy for breast cancer patients in New Hampshire.

Methods

We examined New Hampshire State Cancer Registry data on 5630 female breast cancer patients diagnosed from 2010 to 2016. We performed unadjusted and adjusted hierarchical logistic regression to identify factors associated with a patient’s receipt of ODX, being recommended and receiving chemotherapy, and refusing chemotherapy. We calculated intraclass correlation coefficients (ICCs) to examine the proportion of variance in clinical decisions explained by between-physician and between-hospital variation.

Results

Over the study period, 1512 breast cancer patients received ODX. After adjustment for patient and tumor characteristics, we found that patients seen by a male medical oncologist were less likely to be recommended chemotherapy following ODX (OR = 0.50 (95% CI = 0.34–0.74), p < 0.01). Medical oncologists with more clinical experience (reference: less than 10 years) were more likely to recommend chemotherapy (20–29 years: OR = 4.05 (95% CI = 1.57–10.43), p < 0.01; > 29 years: OR = 4.48 (95% CI = 1.68–11.95), p < 0.01). A substantial amount of the variation in receiving chemotherapy was due to variation between physicians, particularly among low risk patients (ICC = 0.33).

Conclusions

In addition to patient clinicopathologic characteristics, physician gender and clinical experience were associated with chemotherapy treatment following ODX testing. The significant variation between physicians indicates the potential for interventions to reduce variation in care.
Survival analysis of patients with stage T2a and T2b perihilar cholangiocarcinoma treated with radical resection
Authors: Zhao Jian , Zhang Wei , Zhang Jun , Zhang Yi , Ma Wen-Jie , Liu Si-Yun , Li Fu-Yu , Song Bin
Published: September 2020

Background

Both the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging system for perihilar cholangiocarcinoma (pCCA) had the same definition for T2a and T2b. But the value of this classification as prognostic factor remains unclear.

Methods

178 patients with stage T2a or T2b who underwent curative intent resection for pCCA between Jan 2010 and Dec 2018 were enrolled. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate Cox regression analysis. The overall survival (OS) were calculated by Kaplan-Meier method.

Results

There was no significant difference in OS between T2a and T2b groups, and the median OS duration were 37 and 31 months (P = 0.354). Both the 7th and 8th edition of the AJCC TNM staging demonstrated a poor prognostic predictive performance. High level of preoperative AST (≥85.0 IU/L) and CA19–9 (≥1000 U/mL), vascular resection and lower pathological differentiation of the tumor were the independent predictors for poor survival after resection.

Conclusion

The newly released 8th edition of AJCC staging system demonstrated a poor ability to discriminate the prognosis of patients with stage T2a and T2b pCCA after resection.
Caregiver dissatisfaction with their child’s participation in home activities after pediatric critical illness
Authors: Jarvis Jessica M. , Fayed Nora , Fink Ericka L. , Choong Karen , Khetani Mary A.
Published: September 2020

Background

Pediatric critical care is often accompanied by a variety of functional impairments. Preliminary evidence suggests children’s participation in home activities has a slow trajectory post-pediatric intensive care unit (PICU) discharge, however, additional and more granular knowledge on specific problematic activities is needed to inform patient-centric rehabilitative care. The objectives of this study are to identify common home activities in which caregivers’ report dissatisfaction and to determine predictors of caregivers’ dissatisfaction with their child’s participation in home activities post-PICU discharge.

Methods

Secondary analyses of data from a prospective cohort study, the Wee-Cover study, using a subsample of caregivers (N = 170) of children 1–17 years, admitted to a PICU ≥48 h with data on our primary outcome measure from at least one time point. Data were gathered at enrollment and at 3 and 6 months post-PICU discharge. Caregivers reported on their dissatisfaction with their child’s participation in home activities via the Participation and Environment Measure. Common activities were identified by plotting caregiver dissatisfaction for each activity pre-and post-PICU, reporting activities in which ≥50% of caregivers reported dissatisfaction with post-PICU, and assessing for significantly different dissatisfaction levels between time-points for each activity. Predictors of caregiver dissatisfaction were assessed using Poisson generalized estimated equation models.

Results

There was variability in reported dissatisfaction across all activities; ≥50% of caregivers reported dissatisfaction with five activities, including getting clean, personal care management, and mealtime for younger children and household chores and homework for school-aged children and youth. Four activities had significantly higher caregiver dissatisfaction post-PICU: sleep (children < 5 years), homework, indoor play and games, and computer/video games (children ≥5 years). Home environmental support and the interaction of having participation-focused strategies with receiving PICU-based rehabilitation services were negatively associated with caregiver dissatisfaction. Increased caregiver stress and functional performance were associated with increased dissatisfaction.

Conclusions

Individualized PICU-based rehabilitation services to determine family priorities and develop participation-focused strategies, specifically those increasing environmental supports within the home, may ease the family’s transition home post-PICU.

Trial registration

ClinicalTrials.gov Identifier NCT02148081 05/28/2014.
Prevalence of and risk factors for anxiety and depression in Chinese patients with unruptured intracranial aneurysms treated by endovascular intervention
Authors: Zhai Xiao-Dong , Yu Jia-Xing , Ma Yong-Jie , Xiang Si-Shi , Li Gui-Lin , He Chuan , Hu Peng , Zhang Hong-Qi
Published: September 2020

Background

Studies on anxiety and depression in unruptured intracranial aneurysm (UIA) patients after treatment via endovascular intervention are rare and controversial. We aimed to explore the prevalence of anxiety and depression among Chinese patients with UIAs treated by endovascular intervention and to identify which factors contribute to the development of these symptoms.

Methods

We performed a cross-sectional study on anxiety and depression in patients who underwent endovascular treatment for UIAs using the Hospital Anxiety and Depression Scale (HADS). The demographic, clinical and radiological data for all patients were retrospectively collected from the aneurysm database and medical records. Moreover, we utilized data from a large sample of 200 UIA patients and multivariate logistic regression analysis to investigate the risk factors for anxiety and depression in these patients. Candidate variables with P values less than 0.20 in univariate analysis were included in the multivariate logistic regression analysis.

Results

Two hundred patients returned completed questionnaires in this study. Of these 200 patients, 34 (17.0%) suffered from anxiety and 31 (15.5%) suffered from depression 30.67 ± 8.6 months after being discharged. The multivariate analysis results indicated that shorter sleep times were statistically significantly associated with depression (OR = 1.62, 95% CI: 1.14 ~ 2.29, P = 0.007, Adjusted P = 0.02). .

Conclusion

The prevalences of anxiety and depression in UIA patients treated by endovascular intervention were 17.0 and 15.5%, respectively. Shorter sleep times were significantly associated with depression. Our findings provide evidence for the clinical and psychological management of these patients.
Risk factors of hospitalization for any medical condition among patients with prior emergency department visits for mental health conditions
Authors: Penzenstadler Louise , Gentil Lia , Grenier Guy , Khazaal Yasser , Fleury Marie-Josée
Published: September 2020

Background

This longitudinal study identified risk factors for frequency of hospitalization among patients with any medical condition who had previously visited one of six Quebec (Canada) emergency departments (ED) at least once for mental health (MH) conditions as the primary diagnosis.

Methods

Records of n = 11,367 patients were investigated using administrative databanks (2012–13/2014–15). Hospitalization rates in the 12 months after a first ED visit in 2014–15 were categorized as no hospitalizations (0 times), moderate hospitalizations (1–2 times), and frequent hospitalizations (3+ times). Based on the Andersen Behavioral Model, data on risk factors were gathered for the 2 years prior to the first visit in 2014–15, and were identified as predisposing, enabling or needs factors. They were tested using a hierarchical multinomial logistic regression according to the three groups of hospitalization rate.

Results

Enabling factors accounted for the largest percentage of total variance explained in the study model, followed by needs and predisposing factors. Co-occurring mental disorders (MD)/substance-related disorders (SRD), alcohol-related disorders, depressive disorders, frequency of consultations with outpatient psychiatrists, prior ED visits for any medical condition and number of physicians consulted in specialized care, were risk factors for both moderate and frequent hospitalizations. Schizophrenia spectrum and other psychotic disorders, bipolar disorders, and age (except 12–17 years) were risk factors for moderate hospitalizations, while higher numbers (4+) of overall interventions in local community health service centers were a risk factor for frequent hospitalizations only. Patients with personality disorders, drug-related disorders, suicidal behaviors, and those who visited a psychiatric ED integrated with a general ED in a separate site, or who visited a general ED without psychiatric services were also less likely to be hospitalized. Less urgent and non-urgent illness acuity prevented moderate hospitalizations only.

Conclusions

Patients with severe and complex health conditions, and higher numbers of both prior outpatient psychiatrist consultations and ED visits for medical conditions had more moderate and frequent hospitalizations as compared with non-hospitalized patients. Patients at risk for frequent hospitalizations were more vulnerable overall and had important biopsychosocial problems. Improved primary care and integrated outpatient services may prevent post-ED hospitalization.
Strategies for increasing impact, engagement, and accessibility in HIV prevention programs: suggestions from women in urban high HIV burden counties in the Eastern United States (HPTN 064)
Authors: Abrams Jasmine A. , Odlum Michelle , Tillett Emily , Haley Danielle , Justman Jessica , Hodder Sally , Vo Linda , O’Leary Ann , Frew Paula M. ,   the HIV Prevention Trials Network 064 (HTPN) Study Team
Published: September 2020

Background

Merely having the tools to end HIV is insufficient. Effectively ending the epidemic necessitates addressing barriers that impede engagement in biomedical and behavioral prevention and wide scale implementation and utilization of existing interventions. This qualitative study identifies suggestions for increasing access to, engagement in, and impact of HIV prevention among women living in cities in high HIV burden counties in the eastern US.

Methods

Data analyzed for the current study were collected via a qualitative sub-study within the HIV Prevention Trials Network Study 064 (HPTN 064), a multisite observational cohort study designed to estimate HIV incidence among women residing in communities with elevated HIV prevalence who also reported personal or partner characteristics associated with increased risk of HIV acquisition. Focus group and interview participants in the qualitative sub-study (N = 288) were from four cities in the eastern US.

Results

Thematic analyses revealed four themes describing women’s most frequently stated ideas for improving prevention efforts: 1) Promote Multilevel Empowerment, 2) Create Engaging Program Content, 3) Build “Market Demand”, and 4) Ensure Accessibility. We conducted additional analyses to identify contradictory patterns in the data, which revealed an additional three themes: 1) Address Structural Risk Factors, 2) Increase Engagement via Pleasure Promotion, 3) Expand Awareness of and Access to Prevention Resources.

Conclusions

Findings may be useful for enhancing women’s engagement in and uptake of behavioral and biomedical HIV prevention resources, improving policy, and addressing multilevel risk factors.

Trial registration

Clinicaltrials.gov: NCT00995176, prospectively registered.
Sport participation settings: where and ‘how’ do Australians play sport?
Authors: Eime R. , Harvey J. , Charity M.
Published: September 2020

Background

Leisure-time physical activity and sport participation trends are often reported, both in aggregate and by specific activity. Recently there has been a rise in overall leisure-time physical activity, but little change in the prevalence of organised sport. It is important that the development of sport policy, infrastructure and strategic developments meet the changing landscape of participation. However, there has been relatively little research into the settings in which people participate. The aim of this study is to investigate the settings of participation of children and adults in 12 major Australian sports.

Methods

This study utilised data about participation in sport and recreational physical activity collected in the AusPlay survey from a representative sample of adults and children in the Australian state of Victoria. For each type of physical activity, the settings of participation are identified. Respondents can report participation in a particular activity in more than one setting. Therefore we use the term “instance of participation” to refer to a person playing a particular sport in a particular setting. Participation and settings across 12 major sports were investigated for children and adults.

Results

For children, the most popular sport was swimming with a weighted estimate of 323,565 (30.3%) instances of participation in the Victorian population, followed by Australian football (n = 180,459; 16.9%), and basketball (n = 137,169; 12.9%). For adults the most popular sports were swimming (n = 703,950; 30.9%) followed by golf (n = 274,729; 12.1%), and tennis (n = 260,814; 11.4%). There were considerable differences between the profiles of settings of participation for the 12 sports. Across the 12 sports, the majority of participation by children took place within a sports club or association setting, representing 63% of all instances of sport participation. For adults, sports clubs and associations was also the most popular setting, but it represented only 37% of instances of participation.

Conclusions

Traditionally, community clubs and inter-club competitions provided the main setting for sport participation, but this is no longer the case, particularly for adults. If the community sport sector is to continue to flourish, it must consider new strategies and participation options more attractive to other segments of its potential market.
Hepatitis C virus infection characteristics and treatment outcomes in Canadian immigrants
Authors: Cooper Curtis L. , Read Daniel , Vachon Marie-Louise , Conway Brian , Wong Alexander , Ramji Alnoor , Borgia Sergio , Tam Ed , Barrett Lisa , Smyth Dan , Feld Jordan J. , Lee Sam ,   on behalf of the CANUHC Cohort
Published: September 2020

Background

There are multiple obstacles encountered by immigrants attempting to engage hepatitis C virus (HCV) care and treatment. We evaluated the diversity and treatment outcomes of HCV-infected immigrants evaluated for Direct Acting Antiviral (DAA) therapy in Canada.

Methods

The Canadian Network Undertaking against Hepatitis C (CANUHC) Cohort contains demographic information and DAA treatment information prospectively collected at 10 Canadian sites. Information on country of origin and race are collected. Characteristics and outcomes (sustained virological response; SVR) were compared by immigration status and race.

Results

Between January 2016 and May 2018, 725 HCV-infected patients assessed for DAA therapy were enrolled in CANUHC (mean age: 52.66 ± 12.68 years); 65.66% male; 82.08% White, 5.28% Indigenous, 4.64% South East Asian, 4.64% East Indian, 3.36% Black). 18.48% were born outside of Canada. Mean age was similar [immigrants: 54.36 ± 13.95 years), Canadian-born: 52.27 ± 12.35 years); (p = 0.085)]. The overall baseline fibrosis score (in kPa measured by transient elastography) was similar among Canadian and foreign-born patients. Fibrosis score was not predicted by race or genotype. The proportion initiating DAA therapy was similar by immigrant status (56.72% vs 49.92%). SVR rates by intent-to-treat analysis were similar (immigrants-89.47%, Canadian-born-92.52%; p = 0.575).

Conclusion

A diverse immigrant population is engaging care in Canada, initiating HCV antiviral therapy in an equitable fashion and achieving SVR proportions similar to Canada-born patients. Our Canadian experience may be of value in informing HCV elimination efforts in economically developed regions.
Efficacy and safety of transurethral split of prostate for benign prostatic hyperplasia: a meta-analysis
Authors: Huang Yiyu , LI Jiaxin , Yang Shan , Yuan Daozhang , Wang Shusheng
Published: September 2020

Background

Transurethral resection of the prostate (TURP) is the first choice for the treatment of benign prostatic hyperplasia. However, Transurethral split of prostate (TUSP) also seems to have clear clinical efficacy and clinical promotion value. To better clarify the potential and limitations of this treatment of prostate hyperplasia. This study objectively evaluated the clinical efficacy and safety of TUSP.

Methods

The Pubmed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Database for Chinese Technical Periodicals (VIP), Wanfang (Wanfang data), and SinoMed databases were searched for relevant studies. We then used Revman Manager 5.3 to perform a meta-analysis of all randomized controlled trials that evaluated the efficacy and safety of TUSP versus the classic surgical procedures commonly used in the clinic.

Results

A total of 7 studies involving 592 patients were included. The combined data showed that TUSP can shorten the operation time [MD: -33.68; 95% CI: − 38.45 to − 28.91; P < 0.001], reduce intraoperative blood loss [MD: -56.06; 95% CI: − 62.68 to − 49.43; P < 0.001], shorten the time of indwelling catheter [MD: -1.83; 95% CI: − 1.99 to − 1.67; P < 0.001], shorten the postoperative hospital stay length [MD: -1.61; 95% CI: − 1.90 to − 1.32; P < 0.001] and improved postoperative quality of life score (QOL) [MD: 0.16; 95% CI: 0.02 to 0.29; P = 0.02] compared to traditional surgical approaches. There were no statistically significant differences in international prostate symptom score (IPSS), maximum urinary flow rate (Qmax), residual urine volume (RUV), or complications between TUSP and traditional approached.

Conclusion

TUSP can be an effective alternative for clinical treatment of benign prostatic hyperplasia. Given the limitations of the included studies, more high-quality randomized controlled trials are needed in the future to validate or update the results of this analysis.
Factors associated with induced abortion among women of reproductive age attending selected health facilities in Addis Ababa, Ethiopia: a case control study
Authors: Megersa Bikila Soboka , Ojengbede Oladosu Akanbi , Deckert Andreas , Fawole Olufunmilayo Ibitola
Published: September 2020

Background

There has been a significant reduction of abortion rates in high-income countries, while the rates remain unchanged in low- and middle-income countries. In Ethiopia, for example, the number of women of reproductive age seeking an induced abortion is increasing. However, there is limited information concerning the reasons why the occurrence of this procedure is increasing. Thus, this study aimed to identify factors associated with having induced abortion in Addis Ababa, Ethiopia.

Methods

An unmatched case-control study was conducted using a semi-structured, interviewer-administered questionnaire from October to December 2017. The cases were 147 women of reproductive age who underwent abortion in a health facility or presented with complications due to induced abortion conducted outside the health facility. The controls were 295 women who came for antenatal care and who reported never having had an induced abortion. The cases were selected by consecutive sampling from nine health facilities, whereas the controls were selected by systematic sampling from the same health facilities. Bivariate and multivariate logistic regression models were employed using STATA version 14 to identify factors associated with induced abortion.

Results

The mean age of cases was 26.5 ± 5.7 years, while for the controls it was 28.1 ± 4.8 years. Being unmarried (AOR = 9.6; 95% CI: 1.5–61.7), having primary (AOR = 5.3; 95% CI: 1.5–18.3) and tertiary (AOR = 5.7; 95% CI: 1.6–21.1) education, earning monthly income 100–300 USD (AOR = 0.2; 95% CI: 0.1–0.4) and >  300 USD (AOR = 0.1; 95% CI: 0.0–0.2), initiating first intercourse between ages of 15 and 19 (AOR = 4.7; 95% CI: 1.4–15.6), marrying before the age of 18 (AOR = 2.9; 95% CI: 1.3–6.7), and having two children (AOR = 4.7; 95% CI: 1.8–12.7) were independent predictors of induced abortion.

Conclusion

Family planning programs hoping to reduce the occurrence of induced abortion should specifically target unmarried women, low income, and those who have two children. The government should also work on preventing early marriage and providing sexual and reproductive health education to help adolescents delay age at first sexual experience.
Serum macrophage migration inhibition factor for diagnosing endometriosis and its severity: case-control study
Authors: Elbaradie Sahar Mohamed Yehya , Bakry Mohamed Sobhy , Bosilah Almandouh Hussein
Published: September 2020

Background

Endometriosis is a long-standing progressive disease that affects women of reproductive age. Macrophage migration inhibitory factor (MIF) is one of non-invasive blood biomarker that was detected in sera of endometriotic patients. The present study aimed to determine the accuracy of serum MIF in diagnosing endometriosis in women with infertility and chronic pelvic pain, and correlate its level to the stage of the disease.

Methods

Observational case-control study conducted at Fayoum University hospital from March 2016 till September 2018. Three hundred women candidate for diagnostic laparoscopy for either infertility or gynecologic chronic pelvic pain were included. The study group included patients with symptoms suggestive of endometriosis or chocolate cyst by ultrasound and proved by laparoscopy and histopathology. The control group included other causes of infertility or pelvic pain. All patients undergone either diagnostic or operative laparoscopy, and before laparoscopy blood sampling for quantitative measurement of macrophage migration inhibitory factor (MIF) protein in serum by ELISA technique.

Results

The level of serum MIF was significantly higher in endometriosis group compared to control group (1.75 ± 1.48 pg/ml and 0.51 ± 0.45 pg/ ml, respectively, P = < 0.001), with a progressive increase with advancing stage (stage I, 1.3 ± 1.03 pg/ml, stage II, 1.7 ± 1.57 pg/ml, stage III, 2.1 ± 1.19 pg/ml and in stage IV, 3.2 ± 2.6 pg/ml). Moreover, in patients presented with pain and infertile patients showed significantly higher levels of serum MIF (1.92 ± 1.13 vs 1.21 ± 1.17 and 1.82 ± 1.13 vs 1.32 ± 0.91 respectively with p-value < 0.001). ROC curve of serum MIF with a cut off value of 0.85 pg/ml or more achieves a sensitivity of 80.6%, specificity of 83.3%, positive predictive value of 82.9% and negative predictive value of 81.2%.

Conclusion

Serum MIF might be a promising marker not only for noninvasive diagnosis of endometriosis but as a target for detecting severity as well.
Factors influencing the use of modern contraceptive in Nigeria: a multilevel logistic analysis using linked data from performance monitoring and accountability 2020
Authors: Alo Oluwafemi David , Daini Babajide Oluseyi , Omisile Olugbenga K. , Ubah Ebere Joy , Adelusi Odunayo Esther , Idoko-Asuelimhen Ochanya
Published: September 2020

Background

The population of Nigeria is estimated at over 190 million and it is projected to increase by 44% between 2015 and 2030. However, less than one-quarter of women within reproductive age in Nigeria uses modern contraceptive methods despite its importance. Hence, this study aims at examining the influence of individual and community level factors on the use of modern contraceptive method.

Methods

The study is a secondary analysis of linked household and Service Delivery Point datasets from a 2018 survey conducted by Performance, Monitoring and Accountability in Nigeria. Data was abstracted for a total of 9126 sexually active women within the ages of 15–49 years across 295 enumeration areas in seven States. A 2-level binary logistic regression was used to examine the association between study variables and the use of modern contraceptives while adjusting for the clustering effect.

Results

There was significant influence of educational level, marital status, parity, socio-economic status, fertility intention, and awareness of family planning methods on the use of modern contraceptives. Also, women who perceived support from someone in the community on family planning were more likely to use modern contraceptive unlike those without such support. Those who believed that contraceptive methods are used by almost all and some of their friends or relatives were more likely to use modern contraceptive compared to those who think otherwise.

Conclusions

The study shows the need to reduce inequalities between FP utilization across women with different socio-economic status as well as increasing the awareness for modern contraceptive methods.
How can educators improve the perception of happiness for pre-clinical medical students?
Authors: Ghani Sami Ahmad , Salam Muhammed Aizaz us , Oyekwe George Chukwuemeka , Choudhury Sharfraz Riaz
Published: September 2020

As medical students, we recognise how the various stages of medical school can influence one’s perception of their educational environment, as illustrated by the work of Yoo and Kim. Throughout this article, via the exploration of reviewed literature and personal experience, we provide a critical perspective into the significance of enhancing student happiness within pre-clinical periods of the medical curriculum. Here, we highlight the refinements and safeguards available which we believe should be taken into consideration by educators.
South Africa’s new standard material transfer agreement: proposals for improvement and pointers for implementation
Authors: Thaldar Donrich W. , Botes Marietjie , Nienaber Annelize
Published: September 2020

Background

Whenever South African (SA) research institutions share human biological material and associated data for health research or clinical trials they are legally compelled to have a material transfer agreement (MTA) in place that uses as framework the standard MTA newly gazetted by the South African Minister of Health (SA MTA).

Main body

The article offers a legal analysis of the SA MTA and focuses on its substantive fit with the broader legal environment in South Africa, and the clarity and practicality of its terms. The following problematic aspects of the SA MTA are highlighted: (a) Where only data and no human biological material are transferred, the SA MTA does not apply, leaving a lacuna; (b) Health Research Ethics Committees are required to be parties to a MTA despite it being outside their legal mandate and undermining their oversight function; (c) the SA MTA’s consent provisions are not aligned with extant law; and, similarly, (d) its provision on donor ownership is misaligned with extant law; (e) its creation of fictitious performance can only cause frustration on the part of an injured party; (f) its benefit-sharing provision is vague and will have little practical effect; (g) its dispute-resolution provisions fail to adequately protect South African research institutions and research participants; (h) it fails to provide substantive guidance regarding intellectual property as its provisions relating to intellectual property may cause practical problems; and, finally, (i) its data privacy provision is insufficiently specific, is overbroad, and fails to provide terms that in general would facilitate the international sharing of human biological material and associated data in terms of existing privacy law.

Conclusions

While some of the problematic aspects of the SA MTA are intricate and require consultative processes with stakeholders and others, to develop comprehensive solutions, most of the problematic aspects can be resolved immediately through amendments by the South African Minister of Health. The formulation of such amendments is proposed and, where possible, interim measures are suggested that may ameliorate the problems presented by the SA MTA.
Identification of most influential co-occurring gene suites for gastrointestinal cancer using biomedical literature mining and graph-based influence maximization
Authors: Wang Charles C. N. , Jin Jennifer , Chang Jan-Gowth , Hayakawa Masahiro , Kitazawa Atsushi , Tsai Jeffrey J. P. , Sheu Phillip C.-Y.
Published: September 2020

Background

Gastrointestinal (GI) cancer including colorectal cancer, gastric cancer, pancreatic cancer, etc., are among the most frequent malignancies diagnosed annually and represent a major public health problem worldwide.

Methods

This paper reports an aided curation pipeline to identify potential influential genes for gastrointestinal cancer. The curation pipeline integrates biomedical literature to identify named entities by Bi-LSTM-CNN-CRF methods. The entities and their associations can be used to construct a graph, and from which we can compute the sets of co-occurring genes that are the most influential based on an influence maximization algorithm.

Results

The sets of co-occurring genes that are the most influential that we discover include RARA - CRBP1, CASP3 - BCL2, BCL2 - CASP3 – CRBP1, RARA - CASP3 – CRBP1, FOXJ1 - RASSF3 - ESR1, FOXJ1 - RASSF1A - ESR1, FOXJ1 - RASSF1A - TNFAIP8 - ESR1. With TCGA and functional and pathway enrichment analysis, we prove the proposed approach works well in the context of gastrointestinal cancer.

Conclusions

Our pipeline that uses text mining to identify objects and relationships to construct a graph and uses graph-based influence maximization to discover the most influential co-occurring genes presents a viable direction to assist knowledge discovery for clinical applications.
LSTrAP-Crowd: prediction of novel components of bacterial ribosomes with crowd-sourced analysis of RNA sequencing data
Authors: Hew Benedict , Tan Qiao Wen , Goh William , Ng Jonathan Wei Xiong , Mutwil Marek
Published: September 2020

Background

Bacterial resistance to antibiotics is a growing health problem that is projected to cause more deaths than cancer by 2050. Consequently, novel antibiotics are urgently needed. Since more than half of the available antibiotics target the structurally conserved bacterial ribosomes, factors involved in protein synthesis are thus prime targets for the development of novel antibiotics. However, experimental identification of these potential antibiotic target proteins can be labor-intensive and challenging, as these proteins are likely to be poorly characterized and specific to few bacteria. Here, we use a bioinformatics approach to identify novel components of protein synthesis.

Results

In order to identify these novel proteins, we established a Large-Scale Transcriptomic Analysis Pipeline in Crowd (LSTrAP-Crowd), where 285 individuals processed 26 terabytes of RNA-sequencing data of the 17 most notorious bacterial pathogens. In total, the crowd processed 26,269 RNA-seq experiments and used the data to construct gene co-expression networks, which were used to identify more than a hundred uncharacterized genes that were transcriptionally associated with protein synthesis. We provide the identity of these genes together with the processed gene expression data.

Conclusions

We identified genes related to protein synthesis in common bacterial pathogens and thus provide a resource of potential antibiotic development targets for experimental validation. The data can be used to explore additional vulnerabilities of bacteria, while our approach demonstrates how the processing of gene expression data can be easily crowd-sourced.
Endemicity of Taenia solium cysticercosis in pigs from Mbeya Rural and Mbozi districts, Tanzania
Authors: Kabululu Mwemezi L. , Ngowi Helena A. , Mlangwa James E. D. , Mkupasi Ernatus M. , Braae Uffe C. , Trevisan Chiara , Colston Angela , Cordel Claudia , Johansen Maria V.
Published: September 2020

Background

Taenia solium taeniasis/cysticercosis is a disease of substantial economic and public health importance particularly in low–income countries. The disease was reported to be endemic in Mbeya Rural and Mbozi districts, in the southern highlands of Tanzania, the major pig production area in the country. In 2008, using B158/B60 antigen detection enzyme–linked immunosorbent assay (Ag–ELISA), porcine cysticercosis prevalence of up to 32% was reported in the districts. A number of interventions have been implemented in selected villages including an integrated approach consisting of improving pig confinement and selective treatment of pigs with oxfendazole. Mass drug administration with praziquantel targeting schistosomiasis, with an expected effect on T. solium, was also provided to school–age children in the area. This study aimed at providing an update on prevalence and intensities of porcine cysticercosis; and assessing farmers’ knowledge, attitudes and practices which could be associated to disease transmission in the area. The study involved a questionnaire survey conducted using face–to–face household interviews with 890 consenting farmers; and carcass dissections performed on 282 pigs randomly selected from the surveyed households.

Results

Twenty–six pigs (9.2%) were infected with T. solium; of which two–thirds (65.4%) had light to moderate infection intensities (1–1000 cysticerci), and one–third (34.6%) had heavy intensities (> 1000 cysticerci). Questionnaire results showed that only 5.7% of the respondents perceived T. solium cysticercosis to be an important disease in pigs. About 18.5% of the respondents were aware of T. solium taeniasis, but 32% of them were unaware of how the infection is acquired. Half of the respondents had seen cysticerci in pork, of whom 61% were not aware that consumption of infected pork could cause taeniasis. Latrines were observed to often (90%) lack doors with 45% considered accessible to pigs.

Conclusions

This study provided an evidence that the disease was still endemic in the area. Poor knowledge of farmers, attitudes, and risky practices responsible for disease perpetuation were also revealed. A One Health approach targeting the whole area incorporating improvement of farmer knowledge regarding disease transmission needs to be trialed as a feasible approach to control.
CRISPR interference-guided modulation of glucose pathways to boost aconitic acid production in Escherichia coli
Authors: Li Qingyang , Zhao Peng , Yin Hang , Liu Zhaonan , Zhao Haifeng , Tian Pingfang
Published: September 2020

Background

One major mission of microbial breeding is high-level production of desired metabolites. Overproduction of intermediate metabolites in core pathways is challenging as it may impair cell growth and viability.

Results

Here we report that aconitic acid, an intermediate metabolite in tricarboxylic acid (TCA) cycle, can be overproduced by an engineered CRISPR interference (CRISPRi) system in Escherichia coli. This CRISPRi system was designed to simultaneously target pyruvate kinase (PK) and isocitrate dehydrogenase (IDH), two enzymes in glycolytic pathway and TCA cycle, respectively. Reverse transcription and quantitative PCR and enzyme activity assays showed that this engineered CRISPRi system significantly repressed the genes encoding IDH and PK, resulting in simultaneous reduction in the activities of IDH and PK. In shake-flask and fed-batch cultivation, this CRISPRi strain produced 60-fold (362.80 ± 22.05 mg/L) and 15-fold (623.80 ± 20.05 mg/L) of aconitic acid relative to the control strain, respectively. In addition, this two-target CRISPRi strain maintained low levels of acetate and lactate, two problematic byproducts.

Conclusions

This work demonstrates that CRISPRi system can improve aconitic acid production by coordinating glycolysis and TCA cycle. This study provides insights for high-level production of the intermediate metabolites in central pathways.
Bacillus subtilis: a universal cell factory for industry, agriculture, biomaterials and medicine
Authors: Su Yuan , Liu Chuan , Fang Huan , Zhang Dawei
Published: September 2020

Due to its clear inherited backgrounds as well as simple and diverse genetic manipulation systems, Bacillus subtilis is the key Gram-positive model bacterium for studies on physiology and metabolism. Furthermore, due to its highly efficient protein secretion system and adaptable metabolism, it has been widely used as a cell factory for microbial production of chemicals, enzymes, and antimicrobial materials for industry, agriculture, and medicine. In this mini-review, we first summarize the basic genetic manipulation tools and expression systems for this bacterium, including traditional methods and novel engineering systems. Secondly, we briefly introduce its applications in the production of chemicals and enzymes, and summarize its advantages, mainly focusing on some noteworthy products and recent progress in the engineering of B. subtilis. Finally, this review also covers applications such as microbial additives and antimicrobials, as well as biofilm systems and spore formation. We hope to provide an overview for novice researchers in this area, offering them a better understanding of B. subtilis and its applications.
EIF3J-AS1 promotes glioma cell growth via up-regulating ANXA11 through sponging miR-1343-3p
Authors: Qi Jianguo , Wang Zhengrui , Zhao Zhensheng , Liu Lijun
Published: September 2020

Background

Glioma is one prevalent malignant tumor originates from the central nervous system. Dysregulation of long non-coding RNAs (lncRNAs) has been found to be a molecular signature behind the pathology of a variety of cancers, including glioma. EIF3J antisense RNA 1 (EIF3J-AS1) is a novel lncRNA, whose performance in carcinogenesis has been unfolded. Nevertheless, the role of EIF3J-AS1 has never been investigated in glioma.

Methods

qRT-PCR analysis was adopted to evaluate the relative levels of RNAs. In vitro functional assays, including colony formation, EdU, TUNEL and caspase-3/8/9 activity assays were conducted to study the impacts of EIF3J-AS1 on glioma. Dual-luciferase activity assays, RNA pull down assay and RIP assay were performed to elucidate molecular interplay among genes.

Results

EIF3J-AS1 was overexpressed in glioma cell lines. Knockdown of EIF3J-AS1 hampered glioma malignant phenotypes. MiR-1343-3p could bind to EIF3J-AS1. Moreover, miR-1343-3p targeted Annexin A11 (ANXA11) in its 3′UTR region. Mechanistically, EIF3J-AS1 relieved ANXA11 from miR-1343-3p silencing in the EIF3J-AS1/miR-1343-3p/ANXA11 RNA induced silencing complex (RISC), thus eliciting promoting effects on glioma progression. MiR-1343-3p inhibitor and ANXA11 overexpression offset the inhibitory impacts of EIF3J-AS1 silencing on glioma development.

Conclusion

EIF3J-AS1/miR-1343-3p/ANXA11 axis significantly affected biological behaviors in glioma, suggesting new therapeutic target for glioma treatment.