bluuebunny/crossref_metadata_2025 huggingface dataset:
pyCancerSig: subclassifying human cancer with comprehensive single nucleotide, structural and microsatellite mutational signature deconstruction from whole genome sequencing
Authors: Thutkawkorapin Jessada , Eisfeldt Jesper , Tham Emma , Nilsson Daniel
Published: April 2020

Background

DNA damage accumulates over the course of cancer development. The often-substantial amount of somatic mutations in cancer poses a challenge to traditional methods to characterize tumors based on driver mutations. However, advances in machine learning technology can take advantage of this substantial amount of data.

Results

We developed a command line interface python package, pyCancerSig, to perform sample profiling by integrating single nucleotide variation (SNV), structural variation (SV) and microsatellite instability (MSI) profiles into a unified profile. It also provides a command to decipher underlying cancer processes, employing an unsupervised learning technique, Non-negative Matrix Factorization, and a command to visualize the results. The package accepts common standard file formats (vcf, bam). The program was evaluated using a cohort of breast- and colorectal cancer from The Cancer Genome Atlas project (TCGA). The result showed that by integrating multiple mutations modes, the tool can correctly identify cases with known clear mutational signatures and can strengthen signatures in cases with unclear signal from an SNV-only profile. The software package is available at https://github.com/jessada/pyCancerSig.

Conclusions

pyCancerSig has demonstrated its capability in identifying known and unknown cancer processes, and at the same time, illuminates the association within and between the mutation modes.
Label free proteomics and systematic analysis of secretome reveals effector candidates regulated by SGE1 and FTF1 in the plant pathogen Fusarium oxysporum f. sp. cubense tropical race 4
Authors: Zhao Shixue , An Bang , Guo Yanhua , Hou Xingrong , Luo Hongli , He Chaozu , Wang Qiannan
Published: April 2020

Background

Phytopathogens secreted effectors during host colonization to suppress or trigger plant immunity. Identification of new effectors is one of the research focuses in recent years. There is only a limited knowledge about effectors of Fusarium oxysporum f. sp. Cubense tropical race 4 (Foc TR4), the causal agent of wilt disease in Cavendish banana.

Results

Two transcription factors, SGE1 and FTF1, were constitutively over-expressed in Foc TR4 to partially mimic the in-planta state. Secreted proteins with high purity were prepared through a two-round extraction method. Then the secretome were analyzed via label free proteomics method. A total of 919 non-redundant proteins were detected, of which 74 proteins were predicted to be effector candidates. Among these candidates, 29 were up-regulated and 13 down-regulated in the strain over-expressing SGE1 and FTF1, 8 were up-regulated and 4 down-regulated in either SGE1 or FTF1 over expression strain.

Conclusions

Through label free proteomics analysis, a series of effector candidates were identified in secretome of Foc TR4. Our work put a foundation for functional research of these effectors.
Transcriptomic and metabolomic analyses reveal mechanisms of adaptation to salinity in which carbon and nitrogen metabolism is altered in sugar beet roots
Authors: Liu Lei , Wang Bin , Liu Dan , Zou Chunlei , Wu Peiran , Wang Ziyang , Wang Yubo , Li Caifeng
Published: April 2020

Background

Beta vulgarisL. is one of the main sugar-producing crop species and is highly adaptable to saline soil. This study explored the alterations to the carbon and nitrogen metabolism mechanisms enabling the roots of sugar beet seedlings to adapt to salinity.

Results

The ionome, metabolome, and transcriptome of the roots of sugar beet seedlings were evaluated after 1 day (short term) and 7 days (long term) of 300 mM Na+treatment. Salt stress caused reactive oxygen species (ROS) damage and ion toxicity in the roots. Interestingly, under salt stress, the increase in the Na+/K+ratio compared to the control ratio on day 7 was lower than that on day 1 in the roots. The transcriptomic results showed that a large number of differentially expressed genes (DEGs) were enriched in various metabolic pathways. A total of 1279 and 903 DEGs were identified on days 1 and 7, respectively, and were mapped mainly to 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Most of the genes were involved in carbon metabolism and amino acid (AA) biosynthesis. Furthermore, metabolomic analysis revealed that sucrose metabolism and the activity of the tricarboxylic acid (TCA) cycle increased in response to salt stress. After 1 day of stress, the content of sucrose decreased, whereas the content of organic acids (OAs) such as L-malic acid and 2-oxoglutaric acid increased. After 7 days of salt stress, nitrogen-containing metabolites such as AAs, betaine, melatonin, and (S)-2-aminobutyric acid increased significantly. In addition, multiomic analysis revealed that the expression of the gene encoding xanthine dehydrogenase (XDH) was upregulated and that the expression of the gene encoding allantoinase (ALN) was significantly downregulated, resulting in a large accumulation of allantoin. Correlation analysis revealed that most genes were significantly related to only allantoin and xanthosine.

Conclusions

Our study demonstrated that carbon and nitrogen metabolism was altered in the roots of sugar beet plants under salt stress. Nitrogen metabolism plays a major role in the late stages of salt stress. Allantoin, which is involved in the purine metabolic pathway, may be a key regulator of sugar beet salt tolerance.
Evaluation of the effectiveness of high-risk human papilloma self-sampling test for cervical cancer screening in Bolivia
Authors: Allende Gustavo , Surriabre Pedro , Ovando Neli , Calle Pamela , Torrico Andrea , Villarroel Jaime , Bossens Michel , Fontaine Véronique , Rodriguez Patricia
Published: April 2020

Background

In Bolivia the incidence and mortality rates of uterine cervix cancer are the highest in America. The main factor contributing to this situation is the difficulty of establishing and maintaining quality prevention programs based on cytology. We aimed to evaluate the effectiveness of HR-HPV testing on self-collected samples to detect cervical intra-epithelial neoplasia and identify the best combination of screening tests.

Methods

A total of 469 women, divided in two groups, were included in this study. The first group included 362 women that underwent three consecutively primary screening tests: self-collected sampling for HR-HPV detection, conventional cervical cytology and visual inspection under acetic acid (VIA). The second group included 107 women referred with a positive HR-HPV test that underwent conventional cervical cytology and VIA. The presence of high grade intraepithelial lesion (CIN 2+) or invasive cancer was verified by colposcopy and biopsy.

Result

In the screening group the sensitivity to detect high grade intraepithelial lesion (CIN 2+) or invasive cancer were 100, 76, 44% for the VIA, HR-HPV test and cytology, respectively. In the referred group, the sensitivity to detect high grade intraepithelial lesion (CIN 2+) or invasive cancer by VIA and cytology were 100 and 81%, respectively.

Conclusions

VIA and HR-HPV self-sampling were the best combination to detect CIN2+ lesions. Cytology analysis gave the poorest performance.
Prevalence of neonatal hypothermia and its associated factors in East Africa: a systematic review and meta-analysis
Authors: Beletew Biruk , Mengesha Ayelign , Wudu Mesfin , Abate Melese
Published: April 2020

Background

Neonatal hypothermia is a global health problem and a major factor for neonatal morbidity and mortality, especially in low and middle-income countries. Therefore, this systematic review and meta-analysis aimed to assess the prevalence of neonatal hypothermia and its associated factors in Eastern Africa.

Methods

We used the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines to search electronic databases (PubMed, Cochrane Library and Google Scholar; date of last search: 15 October 2019) for studies reporting the prevalence and associated factors of neonatal hypothermia. The data was extracted in the excel sheet considering prevalence, and categories of associated factors reported. A weighted inverse variance random-effects model was used to estimate the magnitude and the effect size of factors associated with hypothermia. The subgroup analysis was done by country, year of publication, and study design.

Results

A total of 12 potential studies with 20,911 participants were used for the analysis. The pooled prevalence of neonatal hypothermia in East Africa was found to be 57.2% (95%CI; 39.5–75.0). Delay in initiation of breastfeeding (adjusted Odds Ratio(aOR) = 2.83; 95% CI: 1.40–4.26), having neonatal health problem (aOR = 2.68; 95% CI: 1.21–4.15), being low birth weight (aOR =2.16; 95%CI: 1.03–3.29), being preterm(aOR = 4.01; 95%CI: 3.02–5.00), and nighttime delivery (aOR = 4.01; 95% CI:3.02–5.00) were identified associated factors which significantly raises the risk of neonatal hypothermia.

Conclusions

The prevalence of neonatal hypothermia in Eastern Africa remains high. Delay in initiation of breastfeeding, having a neonatal health problem, being low birth weight, preterm, and nighttime delivery were identified associated factors that significantly raises the risk of neonatal hypothermia.
Comparison of serum protein profiles between major depressive disorder and bipolar disorder
Authors: Rhee Sang Jin , Han Dohyun , Lee Yunna , Kim Hyeyoung , Lee Junhee , Lee Kangeun , Shin Hyunsuk , Kim Hyeyoon , Lee Tae Young , Kim Minah , Kim Se Hyun , Ahn Yong Min , Kwon Jun Soo , Ha Kyooseob
Published: April 2020

Background

Major depressive disorder and bipolar disorder are prevalent and debilitating psychiatric disorders that are difficult to distinguish, as their diagnosis is based on behavioural observations and subjective symptoms. Quantitative protein profile analysis might help to objectively distinguish between these disorders and increase our understanding of their pathophysiology. Thus, this study was conducted to compare the peripheral protein profiles between the two disorders.

Methods

Serum samples were collected from 18 subjects with major depressive disorder and 15 subjects with bipolar disorder. After depleting abundant proteins, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and label-free quantification were performed. Data-dependent acquisition data were statistically analysed from the samples of 15 subjects with major depressive disorder and 10 subjects with bipolar disorder who were psychotropic drug-free. Two-sided t-tests were performed for pairwise comparisons of proteomes to detect differentially-expressed proteins (DEPs). Ingenuity Pathway Analysis of canonical pathways, disease and functions, and protein networks based on these DEPs was further conducted.

Results

Fourteen DEPs were significant between subjects with major depressive disorder and those with bipolar disorder. Ras-related protein Rab-7a (t = 5.975, p = 4.3 × 10− 6) and Rho-associated protein kinase 2 (t = 4.782, p = 8.0 × 10− 5) were significantly overexpressed in subjects with major depressive disorder and Exportin-7 (t = -4.520, p = 1.5 × 10− 4) was significantly overexpressed in subjects with bipolar disorder after considering multiple comparisons. Bioinformatics analysis showed that cellular functions and inflammation/immune pathways were significantly different.

Conclusions

Ras-related protein Rab-7a, Rho-associated protein kinase 2, and Exportin-7 were identified as potential peripheral protein candidates to distinguish major depressive disorder and bipolar disorder. Further large sample studies with longitudinal designs and validation processes are warranted.
Are we doing enough? Improved breastfeeding practices at 14 weeks but challenges of non-initiation and early cessation of breastfeeding remain: findings of two consecutive cross-sectional surveys in KwaZulu-Natal, South Africa
Authors: Horwood C. , Haskins L. , Engebretsen I. , Connolly C. , Coutsoudis A. , Spies L.
Published: April 2020

Background

KwaZulu-Natal (KZN) Initiative for breastfeeding support (KIBS) was a multipronged intervention to support the initiation and sustaining of breastfeeding, implemented between 2014 and 2017. We present results of two surveys conducted before and after KIBS implementation to assess changes in infant feeding practices in KZN over this time period.

Methods

Two cross-sectional surveys were conducted in primary health care clinics. Multistage stratified random sampling was used to select clinics and participants. Sample size was calculated to provide district estimates of 14-week exclusive breastfeeding (EBF) rates at baseline (KIBS1), and provincial estimates at endpoint (KIBS2). At KIBS1 the sample required was nine participating clinics in each of 11 districts (99 clinics) with 369 participants per district (N = 4059), and at KIBS2 was 30 clinics in KZN with 30 participants per clinic (N = 900). All caregivers aged ≥15 years attending the clinic with infants aged 13- < 16 weeks were eligible to participate. Data was collected using structured interviews on android devices. Multi-variable logistic regression was used to adjust odds ratios for differences between time points.

Results

At KIBS1 (May2014- March2015), 4172 interviews were conducted with carers, of whom 3659 (87.6%) were mothers. At KIBS2 (January–August 2017), 929 interviews were conducted which included 788 (84.8%) mothers. Among all carers the proportion exclusively breastfeeding was 44.6 and 50.5% (p = 0.1) at KIBS1 and KIBS2 respectively, but greater improvements in EBF were shown among mothers (49.9 vs 59.1: p = 0.02). There were reductions in mixed breastfeeding among all infants (23.2% vs 16.3%; p = 0.016). Although there was no change in the proportion of carers who reported not breastfeeding (31.9% vs 32.8%; p = 0.2), the duration of breastfeeding among mothers who had stopped breastfeeding was longer at KIBS2 compared to KIBS1 (p = 0.0015). Mothers who had returned to work or school were less likely to be breastfeeding (adjusted odds ratio [AOR] 3.76; 95% CI 3.1–4.6), as were HIV positive mothers (AOR 2.1; 95% CI 1.7–2.6).

Conclusion

Despite improvements to exclusive breastfeeding, failure to initiate and sustain breastfeeding is a challenge to achieving optimal breastfeeding practices. Interventions are required to address these challenges and support breastfeeding particularly among working mothers and HIV positive mothers.
Effect of metastatic site on survival in patients with neuroendocrine neoplasms (NENs). An analysis of SEER data from 2010 to 2014
Authors: Trikalinos Nikolaos A. , Tan Benjamin R. , Amin Manik , Liu Jingxia , Govindan Ramaswamy , Morgensztern Daniel
Published: April 2020

Background

Neuroendocrine neoplasms (NENs) display variable behaviors based on origin and grade. We assumed that both tumor origin and the location of metastasis may play a role in survival.

Methods

We queried the SEER database (2010–2014) for patients with an established diagnosis of NENs and documented site of metastasis and identified 2005 patients. Overall survival (OS) at the time points were estimated by the Kaplan-Meier method Cox proportional-hazards models were used to evaluate the relationship of the interested variables and OS.

Results

Lung, liver, bone and brain metastases were observed in 9, 77, 7 and 6% of metastatic patients respectively. In the multivariate model, metastasis locations were significantly associated with worse survival (liver HR: 1.677 (1.226–2.294); (bone metastasis HR: 1.412 (0.965–2.065); brain HR: 1.666 (1.177–2.357)). We produced a scoring system based on site of origin, metastasis location, age, gender, histology and tumor size that can stratify metastatic NEN patients in low, intermediate and high-risk categories to help physicians with decision making.

Conclusion

Site of metastasis plays an important role in survival of metastatic NEN patients independent of commonly described prognostic factors and should be considered in survival estimates.
Prevalence and determinants of modern contraceptive utilization among rural lactating mothers: findings from the primary health care project in two northwest Ethiopian districts
Authors: Derso Terefe , Biks Gashaw Andargie , Yitayal Mezgebu , Ayele Tadesse Awoke , Alemu Kassahun , Demissie Getu Debalkie , Wolde Haileab Fekadu , Dellie Endalkachew , Azale Telake , Misganaw Bisrat , Kebede Adane , Fetene Destaw , Gebremdhin Tsegaye , Atnafu Asmamaw
Published: April 2020

Background

Contraceptive utilization is a guarantee to avert unwanted pregnancies. In Ethiopia however, more than half of the rural women have shorter birth intervals. Consequently, 17 and 8% of the births have been either mistimed (wanted at later date) or unwanted, respectively. Therefore, this study investigated modern contraceptive utilization and its predictors among rural lactating women.

Methods

A community based-cross-sectional study was conducted from May 01 to June 29, 2019, in Dabat and Gondar zuria districts, northwest Ethiopia. Data from 603 lactating mother were collected through face to face interviews using a structured questionnaire. Bivariate and multivariate logistic regression analyses were fitted to identify the independent predictors of modern contraceptive utilization.

Results

The overall prevalence of modern contraceptive (MC) utilization rate was 45.8% [95% CI: 38.01, 53.59]. The contraceptive method mix was dominated by Depo-Provera (39.8%) followed by implants (4.8%). The odds of utilization of contraceptive were 5.58 times higher among mothers of children with fully immunized [AOR = 5.58, 95% CI: 3.45, 9.01] compared to mothers whose children were vaccinated partially or not at all. Mothers who received antenatal [AOR = 1.74, 95% CI: 1.13, 4.43] and postnatal care [AOR = 2.02, 95%CI: 1.24, 2.91) were 1.74 and 2.02 folds more likely to utilize modern contraceptives than mothers who did not receive such care, respectively.

Conclusion

The prevalence of modern contraceptive utilization in this study area was lower than the planed national target. In the region, child immunization service is one of the promising platforms for reaching lactating mothers with modern contraceptive utilization. Our findings suggest that antenatal and postnatal care visits are the other key determinants of modern contraceptive utilization. Thus, in low-resource settings like ours, the health system approaches to improved antenatal and, postnatal care and child immunization services should be intensified with more effective advice on modern contraceptive utilization to reduce unwanted pregnancies.
The long-term health effects of attending a selective school: a natural experiment
Authors: Butler Jessica , Black Corri , Craig Peter , Dibben Chris , Dundas Ruth , Hilton Boon Michelle , Johnston Marjorie , Popham Frank
Published: April 2020

Background

Education is widely associated with better physical and mental health, but isolating its causal effect is difficult because education is linked with many socioeconomic advantages. One way to isolate education’s effect is to consider environments where similar students are assigned to different educational experiences based on objective criteria. Here we measure the health effects of assignment to selective schooling based on test score, a widely debated educational policy.

Methods

In 1960s Britain, children were assigned to secondary schools via a test taken at age 11. We used regression discontinuity analysis to measure health differences in 5039 people who were separated into selective and non-selective schools this way. We measured selective schooling’s effect on six outcomes: mid-life self-reports of health, mental health, and life limitation due to health, as well as chronic disease burden derived from hospital records in mid-life and later life, and the likelihood of dying prematurely. The analysis plan was accepted as a registered report while we were blind to the health outcome data.

Results

Effect estimates for selective schooling were as follows: self-reported health, 0.1 worse on a 4-point scale (95%CI − 0.2 to 0); mental health, 0.2 worse on a 16-point scale (− 0.5 to 0.1); likelihood of life limitation due to health, 5 percentage points higher (− 1 to 10); mid-life chronic disease diagnoses, 3 fewer/100 people (− 9 to + 4); late-life chronic disease diagnoses, 9 more/100 people (− 3 to + 20); and risk of dying before age 60, no difference (− 2 to 3 percentage points). Extensive sensitivity analyses gave estimates consistent with these results. In summary, effects ranged from 0.10–0.15 standard deviations worse for self-reported health, and from 0.02 standard deviations better to 0.07 worse for records-derived health. However, they were too imprecise to allow the conclusion that selective schooling was detrimental.

Conclusions

We found that people who attended selective secondary school had more advantaged economic backgrounds, higher IQs, higher likelihood of getting a university degree, and better health. However, we did not find that selective schooling itself improved health. This lack of a positive influence of selective secondary schooling on health was consistent despite varying a wide range of model assumptions.
Convolutional neural network models for cancer type prediction based on gene expression
Authors: Mostavi Milad , Chiu Yu-Chiao , Huang Yufei , Chen Yidong
Published: April 2020

Background

Precise prediction of cancer types is vital for cancer diagnosis and therapy. Through a predictive model, important cancer marker genes can be inferred. Several studies have attempted to build machine learning models for this task however none has taken into consideration the effects of tissue of origin that can potentially bias the identification of cancer markers.

Results

In this paper, we introduced several Convolutional Neural Network (CNN) models that take unstructured gene expression inputs to classify tumor and non-tumor samples into their designated cancer types or as normal. Based on different designs of gene embeddings and convolution schemes, we implemented three CNN models: 1D-CNN, 2D-Vanilla-CNN, and 2D-Hybrid-CNN. The models were trained and tested on gene expression profiles from combined 10,340 samples of 33 cancer types and 713 matched normal tissues of The Cancer Genome Atlas (TCGA). Our models achieved excellent prediction accuracies (93.9–95.0%) among 34 classes (33 cancers and normal). Furthermore, we interpreted one of the models, 1D-CNN model, with a guided saliency technique and identified a total of 2090 cancer markers (108 per class on average). The concordance of differential expression of these markers between the cancer type they represent and others is confirmed. In breast cancer, for instance, our model identified well-known markers, such as GATA3 and ESR1. Finally, we extended the 1D-CNN model for the prediction of breast cancer subtypes and achieved an average accuracy of 88.42% among 5 subtypes. The codes can be found at https://github.com/chenlabgccri/CancerTypePrediction.

Conclusions

Here we present novel CNN designs for accurate and simultaneous cancer/normal and cancer types prediction based on gene expression profiles, and unique model interpretation scheme to elucidate biologically relevance of cancer marker genes after eliminating the effects of tissue-of-origin. The proposed model has light hyperparameters to be trained and thus can be easily adapted to facilitate cancer diagnosis in the future.
Prediction of circRNA-disease associations based on inductive matrix completion
Authors: Li Menglu , Liu Mengya , Bin Yannan , Xia Junfeng
Published: April 2020

Background

Currently, numerous studies indicate that circular RNA (circRNA) is associated with various human complex diseases. While identifying disease-related circRNAs in vivo is time- and labor-consuming, a feasible and effective computational method to predict circRNA-disease associations is worthy of more studies.

Results

Here, we present a new method called SIMCCDA (Speedup Inductive Matrix Completion for CircRNA-Disease Associations prediction) to predict circRNA-disease associations. Based on known circRNA-disease associations, circRNA sequence similarity, disease semantic similarity, and the computed Gaussian interaction profile kernel similarity, we used speedup inductive matrix completion to construct the model. The proposed SIMCCDA method obtains an area under ROC curve (AUC) of 0.8465 with leave-one-out cross validation in the dataset, which is obtained by the combination of the three databases (circRNA disease, circ2Disease and circR2Disease). Our method surpasses other state-of-art models in predicting circRNA-disease associations. Furthermore, we conducted case studies in breast cancer, stomach cancer and colorectal cancer for further performance evaluation.

Conclusion

All the results show reliable prediction ability of SIMCCDA. We anticipate that SIMCCDA could be utilized to facilitate further developments in the field and follow-up investigations by biomedical researchers.
Comprehensive chromosomal aberrations in a case of a patient with TCF3-HLF-positive BCP-ALL
Authors: Lejman Monika , Włodarczyk Monika , Zawitkowska Joanna , Kowalczyk Jerzy R.
Published: April 2020

Background

The use of high-throughput analytical techniques has enabled the description of acute lymphoblastic leukaemia (ALL) subtypes. The TCF3-HLF translocation is a very rare rearrangement in ALL that is associated with an extremely poor prognosis. The TCF3-HLF fusion gene in the described case resulted in the fusion of the homeobox-related gene of TCF3 to the leucine zipper domain of HLF. The TCF3-HLF fusion gene product acts as a transcriptional factor leading to the dedifferentiation of mature B lymphocytes into an immature state (lymphoid stem cells). This process initiates the formation of pre-leukaemic cells. Due to the rarity of this chromosomal aberration, only a few cases have been described in the literature. The advantage of this work is the presentation of an interesting case of clonal evolution of cancer cells and the cumulative implications (diagnostic and prognostic) of the patient’s genetic alterations.

Case presentation

This work presents a patient with diagnosed with TCF3-HLF-positive ALL. Moreover, the additional genetic alterations, which play a key role in the pathogenesis of ALL, were detected in this patient: deletion of a fragment from the long arm of chromosome 13 (13q12.2-q21.1) containing the RB1 gene, intragenic deletions within the PAX5 gene and NOTCH1 intragenic duplication.

Conclusions

A patient with coexistence of chromosomal alterations and the TCF3-HLF fusion has not yet been described. Identifying all these chromosomal aberrations at the time of diagnosis could be sufficient to determine the cumulative effects of the described deletions on the activity of other oncogenes or tumour suppressors, as well as on the clinical course of the disease. On the other hand, complex changes in the patient’s karyotype and clonal evolution of cancer cells call into question the effectiveness of experimental therapy.
YY1-induced lncRNA ZFPM2-AS1 facilitates cell proliferation and invasion in small cell lung cancer via upregulating of TRAF4
Authors: Yan Zhijun , Yang Qilian , Xue Min , Wang Sheng , Hong Weijun , Gao Xiwen
Published: April 2020

Background

Newly identified lncRNA zinc finger protein, FOG family member 2 antisense RNA 1 (ZFPM2-AS1) is identified as an oncogenic gene. However, the role of ZFPM2-AS1 in small cell lung cancer (SCLC) is poorly comprehended.

Methods

The expression of genes in SCLC tissues and cells was measured by qRT-PCR. Colony formation, EdU, CCK-8, transwell and wound healing as well as in vivo assays revealed the function of ZFPM2-AS1 in SCLC. ChIP, luciferase reporter, RIP and RNA pull down assays demonstrated the binding relation among genes.

Results

ZFPM2-AS1 was significantly upregulated in SCLC tissues and cells. ZFPM2-AS1 deficiency attenuated SCLC cell proliferation, invasion and migration. In addition, ZFPM2-AS1 was transcriptionally activated by Yin Yang 1 (YY1) factor. Further, miR-3612 was confirmed as downstream miRNA of ZFPM2-AS1. Moreover, TNF receptor associated factor 4 (TRAF4) was the target gene of miR-3612 in SCLC. ZFPM2-AS1, miR-3612 and TRAF4 jointly constituted a competing endogenous RNA (ceRNA) network in SCLC. Finally, TRAF4 could countervail ZFPM2-AS1 downregulation-mediated function on SCLC cell proliferation and invasion in vitro and tumor growth in vivo.

Conclusion

Our study elucidated the oncogenic effect of ZFPM2-AS1 in SCLC progression, indicating it may be a therapeutic target for SCLC.
Diet and nutrient status of legume consumers in Sweden: a descriptive cross-sectional study
Authors: Steib Céline A. , Johansson Ingegerd , Hefni Mohammed E. , Witthöft Cornelia M.
Published: April 2020

Background

Legumes are nutrient-dense foods and can be an environmentally sustainable alternative to meat consumption. Data on legume intake are scarce and data on legume consumption in Sweden are lacking. This study investigated dietary intake and dietary patterns, together with iron, vitamin D, and folate status, in relation to legume consumption in Sweden.

Methods

Cross-sectional dietary and biomarker data (n 1760) from the 2011 Riksmaten national survey were analyzed. All legume foods (including soy) were identified from 4-day dietary records and ferritin, folate, and vitamin D status in a subgroup (n 280). Participants were classified into non-consumers and quartiles of legume intake. Principal Component Analysis (PCA) was performed to uncover dietary patterns associated with legume intake. Partial Least Square (PLS) regression was used to identify variables associated with variations in legume consumption.

Results

Legumes were consumed by 44% of the population, with mean (SD) intake of 138 (84) g/d in the highest and 11 (5) g/d in the lowest quartiles. Among consumers, 6% reported being vegetarian, compared with 0.9% among non-consumers. Legume consumers drank less alcohol, but had higher intakes of energy, dietary fiber, folate, thiamin, and several minerals, and more often met recommended intake levels for folate and fiber, critical nutrients in Sweden. Biomarker status did not differ with legume intake. PCA revealed multiple loadings on legumes that generally reflected healthier eating habits for legume-consuming women. PLS revealed that vegetarianism was most influential for high legume intake. Other influential variables were high fruit, tea, nut, and seed intakes. High intake of meat, sodas, fast foods, and sweet foods, together with omnivorism, were influential for low legume intake. The associations were similar for men and women.

Conclusions

This study supports dietary recommendations on inclusion of legumes in a healthy diet. Greater focus on assessment of legume intake is necessary to explore the population-wide health effects of legumes as sustainable meat alternatives, and to reinforce national nutritional guidelines.
Association between long-term exposure to ambient air pollution and prevalence of diabetes mellitus among Malaysian adults
Authors: Wong Shew Fung , Yap Poh Sin , Mak Joon Wah , Chan Wan Ling Elaine , Khor Geok Lin , Ambu Stephen , Chu Wan Loy , Mohamad Maria Safura , Ibrahim Wong Norazizah , Ab. Majid Nur Liana , Abd. Hamid Hamizatul Akmal , Rodzlan Hasani Wan Shakira , Mohd Yussoff Muhammad Fadhli bin , Aris Hj. Tahir bin , Ab. Rahman Ezahtulsyahreen Bt. , M. Rashid Zaleha Bt.
Published: April 2020

Background

Malaysia has the highest rate of diabetes mellitus (DM) in the Southeast Asian region, and has ongoing air pollution and periodic haze exposure.

Methods

Diabetes data were derived from the Malaysian National Health and Morbidity Surveys conducted in 2006, 2011 and 2015. The air pollution data (NOx, NO2, SO2, O3 and PM10) were obtained from the Department of Environment Malaysia. Using multiple logistic and linear regression models, the association between long-term exposure to these pollutants and prevalence of diabetes among Malaysian adults was evaluated.

Results

The PM10 concentration decreased from 2006 to 2014, followed by an increase in 2015. Levels of NOx decreased while O3 increased annually. The air pollutant levels based on individual modelled air pollution exposure as measured by the nearest monitoring station were higher than the annual averages of the five pollutants present in the ambient air. The prevalence of overall diabetes increased from 11.4% in 2006 to 21.2% in 2015. The prevalence of known diabetes, underdiagnosed diabetes, overweight and obesity also increased over these years. There were significant positive effect estimates of known diabetes at 1.125 (95% CI, 1.042, 1.213) for PM10, 1.553 (95% CI, 1.328, 1.816) for O3, 1.271 (95% CI, 1.088, 1.486) for SO2, 1.124 (95% CI, 1.048, 1.207) for NO2, and 1.087 (95% CI, 1.024, 1.153) for NOx for NHMS 2006. The adjusted annual average levels of PM10 [1.187 (95% CI, 1.088, 1.294)], O3 [1.701 (95% CI, 1.387, 2.086)], NO2 [1.120 (95% CI, 1.026, 1.222)] and NOx [1.110 (95% CI, 1.028, 1.199)] increased significantly from NHMS 2006 to NHMS 2011 for overall diabetes. This was followed by a significant decreasing trend from NHMS 2011 to 2015 [0.911 for NO2, and 0.910 for NOx].

Conclusion

The findings of this study suggest that long-term exposure to O3 is an important associated factor of underdiagnosed DM risk in Malaysia. PM10, NO2 and NOx may have mixed effect estimates towards the risk of DM, and their roles should be further investigated with other interaction models. Policy and intervention measures should be taken to reduce air pollution in Malaysia.
Preparation, characterization and in vitro–in vivo evaluation of bortezomib supermolecular aggregation nanovehicles
Authors: Chen Ming-yue , Xiao Ze-kuan , Lei Xue-ping , Li Jie-xia , Yu Xi-yong , Zhang Jian-ye , Ye Guo-dong , Guo Yu-juan , Mo Guangquan , Li Chu-wen , Zhang Yu , Zhang Ling-min , Lin Zhi-qiang , Fu Ji-jun
Published: April 2020

Backgrounds

Intolerable toxicity and unsatisfactory therapeutic effects are still big problems retarding the use of chemotherapy against cancer. Nano-drug delivery system promised a lot in increasing the patients’ compliance and therapeutic efficacy. As a unique nano-carrier, supermolecular aggregation nanovehicle has attracted increasing interests due to the following advantages: announcing drug loading efficacy, pronouncing in vivo performance and simplified production process.

Methods

In this study, the supermolecular aggregation nanovehicle of bortezomib (BTZ) was prepared to treat breast cancer.

Results

Although many supermolecular nanovehicles are inclined to disintegrate due to the weak intermolecular interactions among the components, the BTZ supermolecules are satisfying stable. To shed light on the reasons behind this, the forces driving the formation of the nanovehicles were detailed investigated. In other words, the interactions among BTZ and other two components were studied to characterize the nanovehicles and ensure its stability.

Conclusions

Due to the promising tumor targeting ability of the BTZ nanovehicles, the supermolecule displayed promising tumor curing effects and negligible systemic toxicity.
Quality of life after total laryngectomy: impact of different vocal rehabilitation methods in a middle income country
Authors: Souza F. G. R. , Santos I. C. , Bergmann A. , Thuler L. C. S. , Freitas A. S. , Freitas E. Q. , Dias F. L.
Published: April 2020

Introduction

The impact of advanced laryngeal cancer and its extensive surgical treatments cause significant morbidity for these patients. Total laryngectomy impacts essential functions such as breathing, communication and swallowing, and may influence the quality of life as well as affecting the social life of laryngeal cancer patients.

Objective

Describe the quality of life and analyze the factors associated with the reduced quality of life in patients who have undergone total laryngectomy.

Method

Observational cross-sectional study was carried out to evaluate the quality of life of patients who had undergone total laryngectomy due to laryngeal cancer. The fourth version of the UW-QOL Quality of Life Assessment Questionnaire from Washington University, validated for Portuguese, was used.

Results

The study population was 95 patients, and the mean composite score of the QOL was 80.4. In the subjective domains the majority of the patients (38.9%) reported they felt much better at present compared to the month before being diagnosed with cancer. When questioned about how they evaluated their health-related quality of life, there was a predominance of those who considered it good (43.2%), and most considered they had a good quality of life (46.3%) considering personal well-being. The overall quality of life was considered good to excellent by 83.2% of the patients. Patients with tracheoesophageal prosthesis reported a better quality of life, compared to patients using an electrolarynx or esophageal voice.

Conclusion

The high mean value of the composite score for quality of life revealed that the patients assessed their quality of life positively. The absence of vocal emission was the only variable associated with a lower quality of life within the composite score according to the UW-QOL questionnaire.
Palliative bypass surgery for patients with advanced pancreatic adenocarcinoma: experience from a tertiary center
Authors: Pencovich Niv , Orbach Lior , Lessing Yonatan , Elazar Amit , Barnes Sophie , Berman Phillip , Blachar Arye , Nachmany Ido , Sagie Boaz
Published: April 2020

Background

As advances in oncological treatment continue to prolong the survival of patients with non-resectable pancreatic ductal adenocarcinoma (PDAC), decision-making regarding palliative surgical bypass in patients with a heavy disease burden turns challenging. Here we present the results of a pancreatic surgery referral center.

Methods

Patients that underwent palliative gastrojejunostomy and/or hepaticojejunostomy for advanced, non-resectable PDAC between January 2010 and November 2018 were retrospectively assessed. All patients were taken to a purely palliative surgery with no curative intent. The postoperative course as well as short and long-term outcomes was evaluated in relation to preoperative parameters.

Results

Forty-two patients (19 females) underwent palliative bypass. Thirty-one underwent only gastrojejunostomy (22 laparoscopic) and 11 underwent both gastrojejunostomy and hepaticojejunostomy (all by an open approach). Although 34 patients (80.9%) were able to return temporarily to oral intake during the index admission, 15 (35.7%) suffered from a major postoperative complication. Seven patients (16.6%) died from surgery and another seven within the following month. Nine patients (21.4%) never left the hospital following the surgery. Mean length of hospital stay was 18 ± 17 days (range 3–88 days). Mean overall survival was 172.8 ± 179.2 and median survival was 94.5 days. Age, preoperative hypoalbuminemia, sarcopenia, and disseminated disease were associated with palliation failure, defined as inability to regain oral intake, leave the hospital, or early mortality.

Conclusions

Although palliative gastrojejunostomy and hepaticojejunostomy may be beneficial for specific patients, severe postoperative morbidity and high mortality rates are still common. Patient selection remains crucial for achieving acceptable outcomes.
“Children are a blessing from God” – a qualitative study exploring the socio-cultural factors influencing contraceptive use in two Muslim communities in Kenya
Authors: Abdi Batula , Okal Jerry , Serour Gamal , Temmerman Marleen
Published: April 2020

Background

Family planning (FP) is one of the high impact public health interventions with huge potential to enhance the health and wellbeing of women and children. Yet, despite the steady progress made towards expanding access to family planning, major disparities across different regions exist in Kenya. This study explored the socio cultural factors influencing FP use among two Muslim communities in Kenya.

Methods

A qualitative study involving Focus Group Discussions (FGDs) and In-depth Interviews (IDIs) was conducted (from July to October 2018) in two predominant Muslim communities of Lamu and Wajir counties. Open ended questions explore key thematic areas around knowledge, attitudes and understanding of contraception, perceived FP barriers, and decision making for contraceptives, views on Islam and contraception, and fertility preference. All interviews were conducted in the local language, recorded, transcribed verbatim and translated into English. Data was analyzed using thematic content analyses.

Results

Although Islam is the predominant religion the two communities, perceptions and belief around FP use were varied. There were differing interpretations of Islamic teaching and counter arguments on whether or not Islam allows FP use. This, in addition to desire for a large family, polygamy, high child mortality and a cultural preference for boys had a negative impact on FP use. Similarly, inability of women to make decisions on their reproductive health was a factor influencing uptake of FP.

Conclusion

Misinterpretation of Islamic teaching on contraception likely influences uptake of family planning. Cultural beliefs and lack of women’s decision power on fertility preferences were a key inhibitor to FP use. Countering the negative notions of FP use requires active engagement of religious leaders and Muslim scholars who are in position of power and influence at community level.
Identification of a novel B-cell epitope in the spike protein of porcine epidemic diarrhea virus
Authors: Kong Ning , Meng Qiong , Jiao Yajuan , Wu Yongguang , Zuo Yewen , Wang Hua , Sun Dage , Dong Sujie , Zhai Huanjie , Tong Wu , Zheng Hao , Yu Hai , Tong Guangzhi , Xu Yongjie , Shan Tongling
Published: April 2020

Background

Porcine epidemic diarrhea virus (PEDV) infection causes an acute enteric tract infectious disease characterized by vomiting, anorexia, dehydration, weight loss and high mortality in neonatal piglets. During PEDV infection, the spike protein (S) is a major virion structural protein interacting with receptors and inducing neutralizing antibodies. However, the neutralizing B-cell epitopes within PEDV S protein have not been well studied.

Methods

To accurately identify the important immunodominant region of S1, the purified truncated S1 proteins (SA, SB, SC, SD and SE) were used to immunize BALB/c mice to prepare polyclonal antibodies. The antisera titers were determined by indirect ELISA, western blot and IFA after four immunizations to find the important immunodominant region of S1, and then purified the immunodominant region of S1 protein and immunized mice to generate the special antibodies, and then used recombinant peptides to determine the B-cell epitopes of monoclonal antibodies.

Results

Five antisera of recombinant proteins of the spike protein region of PEDV were generated and we found that only the polyclonal antibody against part of the S1 region (signed as SE protein, residues 666–789) could recognize the native PEDV. Purified SE protein was used to immunize BALB/c mice and generate mAb 2E10. Pepscan of the SE protein demonstrated that SE16 (722SSTFNSTREL731) is the minimal linear epitope required for reactivity with the mAb 2E10. Further investigation indicated that the epitope SE16 was localized on the surface of PEDV S protein in the 3D structure.

Conclusions

A mAb 2E10 that is specifically bound to PEDV was generated and identified a specific linear B-cell epitope (SE16,722SSTFNSTREL731) of the mAb. The epitope region of PEDV S1 localized in the different regions in comparison with the earlier identified epitopes. These findings enhance the understanding of the PEDV spike protein structure for vaccine design and provide a potential use for developing diagnostic methods to detect PEDV.
BAck complaints in the elders - chiropractic (BACE-C): protocol of an international cohort study of older adults with low back pain seeking chiropractic care
Authors: Jenks Alan D. , Hoekstra Trynke , Axén Iben , de Luca Katie , Field Jonathan , Newell Dave , Hartvigsen Jan , French Simon D. , Koes Bart , van Tulder Maurits W. , Rubinstein Sidney M.
Published: April 2020

Background

Low back pain is a common condition among older adults that significantly influences physical function and participation. Compared to their younger counterparts, there is limited information available about the clinical course of low back pain in older people, in particularly those presenting for chiropractic care. Improving our understanding of this patient population and the course of their low back pain may provide input for studies researching safer and more effective care than is currently provided.

Objectives

The primary objectives are to examine the clinical course over one year of pain intensity, healthcare costs and pain, functional status and recovery rates of low back pain in people 55 years and older who visit a chiropractor for a new episode of low back pain.

Methods

An international prospective, multi-center cohort study with one-year follow-up. Chiropractic practices are to be recruited in the Netherlands, Sweden, United Kingdom and Australia. Treatment will be left to the discretion of the chiropractor. Inclusion/Exclusion criteria: Patients aged 55 and older who consult a chiropractor for a new episode of low back pain, meaning low back pain for the first time or those patients who have not been to a chiropractor in the previous six months. This is independent of whether they have seen another type of health care provider for the current episode. Patients who are unable to complete the web-based questionnaires because of language restrictions or those with computer literacy restrictions will be excluded as well as those with cognitive disorders. In addition, those with a suspected tumor, fracture, infection or any other potential red flag or condition considered to be a contraindication for chiropractic care will be excluded. Data will be collected using online questionnaires at baseline, and at 2 and 6 weeks and at 3, 6, 9 and 12 months.

Discussion

This study, to our knowledge, is the first large-scale, prospective, multicenter, international cohort study to be conducted in a chiropractic setting to focus on older adults with low back pain consulting a chiropractor. By understanding the clinical course, satisfaction and safety of chiropractic treatment of this common debilitating condition in the aged population, this study will provide input for informing future clinical trials.

Trial registration

Nederlandse Trial Registrar NL7507.