bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative anatomical and transcriptomic insights into Vaccinium corymbosum flower bud and fruit throughout development
Authors: Yang Li , Liu Liangmiao , Wang Zhuoyi , Zong Yu , Yu Lei , Li Yongqaing , Liao Fanglei , Chen Manman , Cai Kailing , Guo Weidong
Published: June 2021

Background

Blueberry (Vaccinium spp.) is characterized by the production of berries that are smaller than most common fruits, and the underlying mechanisms of fruit size in blueberry remain elusive. V. corymbosum ‘O’Neal’ and ‘Bluerain’ are commercial southern highbush blueberry cultivars with large- and small-size fruits, respectively, which mature ‘O’Neal’ fruits are 1 ~ 2-fold heavier than those of ‘Bluerain’. In this study, the ontogenetical patterns of ‘O’Neal’ and ‘Bluerain’ hypanthia and fruits were compared, and comparative transcriptomic analysis was performed during early fruit development.

Results

V. corymbosum ‘O’Neal’ and ‘Bluerain’ hypanthia and fruits exhibited intricate temporal and spatial cell proliferation and expansion patterns. Cell division before anthesis and cell expansion after fertilization were the major restricting factors, and outer mesocarp was the key tissue affecting fruit size variation among blueberry genotypes. Comparative transcriptomic and annotation analysis of differentially expressed genes revealed that the plant hormone signal transduction pathway was enriched, and that jasmonate-related TIFYs genes might be the key components orchestrating other phytohormones and influencing fruit size during early blueberry fruit development.

Conclusions

These results provided detailed ontogenetic evidence for determining blueberry fruit size, and revealed the important roles of phytohormone signal transductions involving in early fruit development. The TIFY genes could be useful as markers for large-size fruit selection in the current breeding programs of blueberry.
Downstream of GA4, PbCYP78A6 participates in regulating cell cycle-related genes and parthenogenesis in pear (Pyrus bretshneideri Rehd.)
Authors: Zhang Haiqi , Han Wei , Wang Huibin , Cong Liu , Zhai Rui , Yang Chengquan , Wang Zhigang , Xu Lingfei
Published: June 2021

Background

Parthenocarpy results in traits attractive to both consumers and breeders, and it overcomes the obstacle of self-incompatibility in the fruit set of horticultural crops, including pear (Pyrus bretshneider). However, there is limited knowledge regarding the genetic and molecular mechanisms that regulate parthenogenesis.

Results

Here, in a transcriptional comparison between pollination-dependent fruit and GA4-induced parthenocarpy, PbCYP78A6 was identified and proposed as a candidate gene involved in parthenocarpy. PbCYP78A6 is similar to Arabidopsis thaliana CYP78A6 and highly expressed in pear hypanthia. The increased PbCYP78A6 expression, as assessed by RT-qPCR, was induced by pollination and GA4 exposure. The ectopic overexpression of PbCYP78A6 contributed to parthenocarpic fruit production in tomato. The PbCYP78A6 expression coincided with fertilized and parthenocarpic fruitlets development and the expression of fruit development-related genes as assessed by cytological observations and RT-qPCR, respectively. PbCYP78A6 RNA interference and overexpression in pear calli revealed that the gene is an upstream regulator of specific fruit development-related genes in pear.

Conclusions

Our findings indicate that PbCYP78A6 plays a critical role in fruit formation and provide insights into controlling parthenocarpy.
The INSPIRE Population Survey: development, dissemination and respondent characteristics
Authors: Siqeca Flaka , Obas Katrina , Yip Olivia , Stenz Samuel , Vounatsou Penelope , Briel Matthias , Schwenkglenks Matthias , Quinto Carlos , Blozik Eva , Zeller Andreas , Zullig Leah L. , De Geest Sabina , Deschodt Mieke
Published: June 2021

Background

Most older adults prefer to continue living at home despite increasing care needs and demand for services. To aid in maintaining independence, integrated care models for community-dwelling older people are promoted as the most cost-effective approach. The implementation of such care models is challenging and often the end-users are not involved or their needs are not considered. We conducted a population survey in order to understand the needs and preferences of home-dwelling older adults living in Canton Basel-Landschaft, Switzerland. The aims of this paper are to chronicle the development of the INSPIRE Population Survey, outline its variables and measurements, describe the marketing strategy utilized for survey dissemination and report on the response rate and respondent characteristics.

Methods

The INSPIRE Population Survey, conducted between March and August 2019, is a cross-sectional survey of older adults aged 75 and older living at home in Canton Basel-Landschaft. The questionnaire was developed by expert input and stakeholder involvement. Its readability and acceptability were pilot-tested with older people. To ensure the likelihood of a high and representative response rate, a meticulous step-by-step marketing strategy was developed prior to the dissemination of the questionnaire.

Results

The overall response rate was 30.7% (n = 8,846), with variations between 20.6 and 34.5% across the different care regions in the canton. A generally higher response rate was found in the care regions with a higher density and which bordered the urban city of Basel. We received support from local stakeholders, policy makers and media through using a broad combination of marketing channels and targeting our community partners who have a strong relationship with our target audience.

Conclusions

Although recruiting older adults in research is challenging, our study shows that a high response rate can be achieved by developing the survey through expert input and by involving all important stakeholders, including older adults, throughout the entire process.
Cerebral large artery stenosis and occlusion in POEMS syndrome
Authors: Sugiyama Atsuhiko , Yokota Hajime , Misawa Sonoko , Mukai Hiroki , Sekiguchi Yukari , Koide Kyosuke , Suichi Tomoki , Matsushima Jun , Kishimoto Takashi , Tanei Zen-ichi , Saito Yuko , Ito Shoichi , Kuwabara Satoshi
Published: June 2021

Background

This study aimed to investigate the frequency and risk factors for cerebral artery stenosis and occlusion in patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome.

Methods

We reviewed results of magnetic resonance angiography (MRA) or computed tomography angiography (CTA) in 61 patients with POEMS syndrome seen between 2010 and 2017. Stenosis or occlusion was assessed in the initial MRA/CTA. Multivariate analysis was used to identify risk factors for artery stenosis/occlusion. In an autopsy case, pathologic examination was conducted of the occluded middle cerebral arteries.

Results

Stenosis (> 50 %) or occlusion of the major cerebral arteries was found in 29 (47.5 %) patients on the initial MRA/CTA. The internal carotid artery was involved most frequently (32.8 %), followed by the anterior (21.3 %) and middle (16.4 %) cerebral arteries. The basilar (1.3 %) and vertebral (3.6 %) arteries were rarely affected. Cerebral infarction developed in eight (13.1 %) patients. The serum vascular endothelial growth factor (VEGF) level was an independent predictor for stenosis/occlusion (odds ratio, 1.228; 95 % confidence interval, 1.042–1.447; P = 0.014). An autopsy study showed occluded middle cerebral arteries by fibrous and myxomatous thickening of intima with splitting of the internal elastic lamina. Follow-up MRA in 23 patients showed improved, worsened, and unchanged stenosis in 20.7 %, 8.7 %, and 69.6 %, respectively.

Conclusions

Cerebral large-vessel stenosis or occlusion is frequently seen in approximately half of patients with POEMS syndrome. Vasculopathy was related to serum VEGF levels and thereby disease activity. Assessment of cerebral vessels is recommended in these patients to improve management.
Impact of the COVID-19 pandemic and post-epidemic periods on the process of endovascular treatment for acute anterior circulation ischaemic stroke
Authors: Zhang Tangqin , Chen Chu , Xu Xiangjun , Xu Junfeng , Yang Ke , Xu Youqing , Yuan Lili , Yang Qian , Huang Xianjun , Zhou Zhiming
Published: June 2021

Background and purpose

The purpose of our study was to analyse endovascular treatment (EVT) in patients presenting acute anterior circulation ischemic stroke with large-vessel occlusion (AIS-LVO) during the pandemic and post-epidemic periods.

Methods

Patients with AIS-LVO of the anterior circulation who underwent EVT were enrolled. According to the times of Wuhan closure and reopening, patients were divided into a pre-pandemic group (from November 8, 2019, to January 22, 2020), pandemic group (from January 23, 2020, to April 8, 2020) and post-epidemic group (from April 9, 2020, to June 24, 2020). The primary endpoints were the time delay among symptom onset to arriving hospital door, to groining puncture and to vascular reperfusion. Secondary endpoints were the functional outcomes evaluated by 90-day modified Rankin scale (mRS) score.

Results

In total, the times from onset to reperfusion (OTR, median 356 min vs. 310 min, p = 0.041) and onset to door (OTD, median 238 min vs. 167 min, p = 0.017) were prolonged in the pandemic group compared to the pre-pandemic group, and the delay continue in the post-epidemic period. In the subgroup analysis, the time from door to imaging (DTI) was significantly prolonged during the pandemic period. Interestingly, the prolonged DTI was corrected in the directly admitted subgroup during post-epidemic period. In addition, the functional outcomes showed no significant differences across the three periods.

Conclusions

Total time and prehospital time were prolonged during the pandemic and post-epidemic periods. Urgent public education and improved in-hospital screening processes are necessary to decrease time delays.
Association between tirofiban monotherapy and efficacy and safety in acute ischemic stroke
Authors: Tao Chunrong , Zhu Yuyou , Zhang Chao , Song Jianlong , Liu Tianlong , Yuan Xiaodong , Luo Wenwu , Chen Changchun , Liu Dezhi , Zhu Yuanyuan , Liu Jie , Hu Wei
Published: June 2021

Background

Studies have suggested that glycoprotein IIb/IIIa antagonists such as tirofiban are beneficial for patients with acute coronary syndromes. However, it is still uncertain about the efficacy and safety of tirofiban in patients with acute ischemic stroke (AIS).

Methods

In this prospective non-randomized study, 255 AIS patients were recruited from 4 comprehensive stroke centers in China between January, 2017 and May, 2018. Among them,169 patients were treated with aspirin plus clopidogrel and 86 patients were treated with tirofiban. The primary functional outcome was the distribution of the 90 days’ modified Rankin Scale (mRS). The safety outcomes included the incidence of intracranial hemorrhage (ICH) at discharge and mortality at 3 months.

Results

In the propensity score matched cohort, tirofiban alone was noninferior to the dual antiplatelet with regard to the primary outcome (adjusted common odds ratio, 0.97; 95% confidence interval, 0.46 to 2.04; P = 0.93). Mortality at 90 days was 10% in the dual antiplatelet group and 8% in the tirofiban group (adjusted odds ratio 0.75; 95% CI 0.08 to 7.40, p = 0.81). There was no difference of the ICH rate between two groups (adjusted odds ratio 0.44; 95% CI 0.13 to 1.48, p = 0.18). In the inverse probability of treatment weighting-propensity score-adjusted cohort, similar differences were found for functional and safety outcomes.

Conclusions

Our study suggested that tirofiban use appears to be safe as monotherapy in AIS treatment compared with common dual antiplatelet therapy, however, no improvement in functional outcomes was found.

Trial registration

Chinese clinical trial registry, ChiCTR2000034443, 05/07/2020. Retrospectively registered.
Multiple sclerosis projection in Tehran, Iran using Bayesian structural time series
Authors: Amini Payam , Almasi-Hashiani Amir , Sahraian Mohammad Ali , Najafi Masood , Eskandarieh Sharareh
Published: June 2021

Background

The prevalence of Multiple Sclerosis (MS) has been increasing worldwide and the highest prevalence ratio among Asian countries was reported in Iran. This study aims to estimate the increase in MS occurrence during more than three decades in Tehran and forecast the future condition of the disease using time series approaches for the next ten years.

Methods

The cross-sectional study was conducted from 1999 to 2019 based on records of MS cases from Iranian MS Society (IMSS) registry system. The prevalence was estimated using population data presented by the Statistical Centre of Iran. Through Bayesian Structural Time Series (BSTS) model, we want to predict the prevalence of familial and sporadic MS in the next ten years. .

Results

Among 22,421 cases with MS, 16,831 (75.1 %) were female and 5589 (24.9 %) were male. Female to male ratio was 3.0:1 and the number of familial MS cases were 2982 (13.3 %) of subjects. Female gender was less responsible for higher rate of MS in familial definition (beta = 0.020) in comparison to sporadic cases (beta = 0.034). Forecasting by BSTS revealed an increase in MS prevalence for the next ten years so that the prevalence rate for total, familial and sporadic MS respectively begins with 189.50 (183.94-195.14), 25.69 (24.97–26.45) and 163.74(159.06-168.57) in 2020 and ends with 220.84 (171.48-266.92), 30.79 (24.16–37.15), and 189.33(146.97-230.19) in 2029.

Conclusions

According to the findings, MS prevalence increased during three decades and it will increase over the next ten years. Tehran province is one of the regions with highest MS prevalence in Asia. The results of present study indicated that females are at higher risk for MS than males in both sporadic and familial MS.
Genome instability-related long non-coding RNA in clear renal cell carcinoma determined using computational biology
Authors: Wang Yutao , Yan Kexin , Wang Linhui , Bi Jianbin
Published: June 2021

Background

There is evidence that long non-coding RNA (lncRNA) is related to genetic stability. However, the complex biological functions of these lncRNAs are unclear.

Method

TCGA - KIRC lncRNAs expression matrix and somatic mutation information data were obtained from TCGA database. “GSVA” package was applied to evaluate the genomic related pathway in each samples. GO and KEGG analysis were performed to show the biological function of lncRNAs-mRNAs. “Survival” package was applied to determine the prognostic significance of lncRNAs. Multivariate Cox proportional hazard regression analysis was applied to conduct lncRNA prognosis model.

Results

In the present study, we applied computational biology to identify genome-related long noncoding RNA and identified 26 novel genomic instability-associated lncRNAs in clear cell renal cell carcinoma. We identified a genome instability-derived six lncRNA-based gene signature that significantly divided clear renal cell samples into high- and low-risk groups. We validated it in test cohorts. To further elucidate the role of the six lncRNAs in the model’s genome stability, we performed a gene set variation analysis (GSVA) on the matrix. We performed Pearson correlation analysis between the GSVA scores of genomic stability-related pathways and lncRNA. It was determined that LINC00460 and LINC01234 could be used as critical factors in this study. They may influence the genome stability of clear cell carcinoma by participating in mediating critical targets in the base excision repair pathway, the DNA replication pathway, homologous recombination, mismatch repair pathway, and the P53 signaling pathway.

Conclusion subsections

These data suggest that LINC00460 and LINC01234 are crucial for the stability of the clear cell renal cell carcinoma genome.
Oral health problems facing refugees in Europe: a scoping review
Authors: Zinah Eiad , Al-Ibrahim Heba M.
Published: June 2021

Introduction

Europe has been experiencing a flow of refugees and asylum seekers driven by conflicts or poverty. Their oral health is often neglected despite its clear impact on quality of life.

Objective

To explore the status of oral health among refugees and asylum seekers groups by examining the available literature and to determine which evidence exists regarding the problems they face in terms of oral health.

Methods

The current paper followed PRISMA guidelines. A scoping review methodology was followed to retrieve 2911 records from five databases and grey literature. Twelve articles met the following inclusion criteria: experimental research concentrated on the oral and dental health of refugees and/or asylum seekers between 1995 and 2020 in English. Analysis was both descriptive and thematic, whilst a critical appraisal was applied using the Critical Appraisal Skills Program (CASP).

Results

Seven studies (58,3%) were quantitative, while five studies (41,6%) were qualitative. In general, the quality of most of the studies (83.3%) was good. Limited access to oral health care services was shown with a higher prevalence of oral diseases compared to the native populations of the host countries. Approaches to improve oral health have been implemented in some studies and have shown positive outcomes.

Conclusions

Oral health care strategies should consider the oral health problems facing refugees in Europe, and oral health promotion campaigns are essential to give adequate guidance on how to access oral health care in the host countries.
The causal effect and impact of reproductive factors on breast cancer using super learner and targeted maximum likelihood estimation: a case-control study in Fars Province, Iran
Authors: Almasi-Hashiani Amir , Nedjat Saharnaz , Ghiasvand Reza , Safiri Saeid , Nazemipour Maryam , Mansournia Nasrin , Mansournia Mohammad Ali
Published: June 2021

Objectives

The relationship between reproductive factors and breast cancer (BC) risk has been investigated in previous studies. Considering the discrepancies in the results, the aim of this study was to estimate the causal effect of reproductive factors on BC risk in a case-control study using the double robust approach of targeted maximum likelihood estimation.

Methods

This is a causal reanalysis of a case-control study done between 2005 and 2008 in Shiraz, Iran, in which 787 confirmed BC cases and 928 controls were enrolled. Targeted maximum likelihood estimation along with super Learner were used to analyze the data, and risk ratio (RR), risk difference (RD), andpopulation attributable fraction (PAF) were reported.

Results

Our findings did not support parity and age at the first pregnancy as risk factors for BC. The risk of BC was higher among postmenopausal women (RR = 3.3, 95% confidence interval (CI) = (2.3, 4.6)), women with the age at first marriage ≥20 years (RR = 1.6, 95% CI = (1.3, 2.1)), and the history of oral contraceptive (OC) use (RR = 1.6, 95% CI = (1.3, 2.1)) or breastfeeding duration ≤60 months (RR = 1.8, 95% CI = (1.3, 2.5)). The PAF for menopause status, breastfeeding duration, and OC use were 40.3% (95% CI = 39.5, 40.6), 27.3% (95% CI = 23.1, 30.8) and 24.4% (95% CI = 10.5, 35.5), respectively.

Conclusions

Postmenopausal women, and women with a higher age at first marriage, shorter duration of breastfeeding, and history of OC use are at the higher risk of BC.
CT-scan based anatomical study as a guidance for infra-acetabular screw placement
Authors: Lu Quanyi , Zhou Runtao , Gao Shichang , Liang Anlin , Yang Mingming , Yang Haitao
Published: June 2021

Background

The infra-acetabular corridor is quite narrow, which makes a challenge for the orthopedists to insert the screw. This study aimed to explore the relationship between the infra-acetabular corridor diameter (IACD) and the minimum thickness of medial acetabular wall (MTMAW), and to clarify the way of screw placement.

Methods

The Computed tomography (CT) data of 100 normal adult pelvises (50 males and 50 females respectively) were collected and pelvis three-dimensional (3D) reconstruction was performed by using Mimics software and the 3D model was imported into Geomagic Studio software. The perspective of acetabulum was carried out orienting from iliopubic eminence to ischial tuberosity and the IACD was measured by placing virtual screws which was vertical to the corridor transverse section of “teardrop”. The relationship between IACD and MTMAW was analyzed. When IACD was ≥5 mm, 3.5 mm all-in screws were placed. When IACD was < 5 mm, 3.5 mm in-out-in screws were placed.

Results

The IACD of males and females were (6.15 ± 1.24) mm and (5.42 ± 1.01) mm and the MTMAW in males and females were (4.40 ± 1.23) mm and (3.60 ± 0.81) mm respectively. The IACD and MTMAW in males were significantly wider than those of females (P < 0.05), and IACD was positively correlated with MTMAW (r = 0.859), the regression equation was IACD = 2.111 + 0.917 MTMAW. In the all-in screw group, 38 cases (76%) were males and 33 cases (66%) were females respectively. The entry point was located at posteromedial of the apex of iliopubic eminence, and the posterior distance and medial distance were (8.03 ± 2.01) mm and (8.49 ± 2.68) mm respectively in males. As for females, those were (8.68 ± 2.35) mm and (8.87 ± 2.79) mm respectively. In the in-out-in screw group, 12 cases (24%) were males and 17 cases (34%) were females, respectively. The posterior distance and medial distance between the entry point and the apex of iliopubic eminence were (10.49 ± 2.58) mm and (6.17 ± 1.84) mm respectively in males. As for females, those were (10.10 ± 2.63) mm and (6.63 ± 1.49) mm respectively. The angle between the infra-acetabular screw and the sagittal plane was medial inclination (0.42 ± 6.49) °in males, lateral inclination (8.09 ± 6.33) °in females, and the angle between the infra-acetabular screw and the coronal plane was posterior inclination (54.06 ± 7.37) °.

Conclusions

The placement mode of the infra-acetabular screw (IAS) can be determined preoperatively by measuring the MTMAW in the CT axial layers. Compared with all-in screw, the in-out-in screw entry point was around 2 mm outwards and backwards, and closer to true pelvic rim.
Ten-year follow up of cosmetic outcome, overall survival, and disease-free survival in endoscope-assisted partial mastectomy with filling of dead space using absorbable mesh for stage ≤ IIA breast cancer: comparison with conventional conservative method
Authors: Takemoto Nobuyuki , Koyanagi Ai , Yamamoto Hiroshi
Published: June 2021

Background

Data on long-term cosmetic outcome, overall survival, and disease-free survival of endoscope-assisted partial mastectomy (EAPM) for breast cancer are scarce. Thus, we examined these outcomes after a 10-year follow-up period, and compared with conventional conservative method (CCM).

Patients and methods

Data on 257 patients with stage ≤ IIA breast cancer who underwent CCM (n = 125) or EAPM (n = 132) were analyzed. Cosmetic outcome at 2, 5, and 10 years was evaluated by 5 criteria (breast retraction assessment, nipple deviation, atrophy, skin change, scar). For overall mortality, breast cancer-specific mortality, and recurrence, the risk by operation method was tested by Cox proportional hazard models.

Results

EAPM performed significantly better than CCM in terms of cosmetic outcomes for location B at 2, 5, and 10 year-follow ups. As for cosmetic outcomes by individual criteria, EAPM had significantly higher proportions of satisfactory results for scar across all follow-up periods, and atrophy at 2-year and 10-year follow-up. There were no significant differences in terms of overall mortality, breast cancer-specific mortality, and recurrence between EAPM and CCM. The rates of patients who experienced local recurrence were similar between CCM and EAPM.

Conclusion

EAPM is better than CCM in terms of long-term cosmetic outcome, especially for location B. As a surgical treatment for breast cancer, EAPM is comparable to CCM in terms of mortality and recurrence.
A cross-sectional study of traditional Chinese medicine practitioner’s knowledge, treatment strategies and integration of practice of chronic pelvic pain in women
Authors: Arentz Susan , Smith Caroline , Redmond Rebecca , Abbott Jason , Armour Mike
Published: June 2021

Background

Chronic pelvic pain (CPP) in women is persistent, intermittent cyclical and non-cyclical lower abdominal pain, lasting for more than 6 months. Traditional Chinese Medicine (TCM) is a popular treatment option for women’s health conditions, but little is known about how treatment for CPP is delivered by TCM practitioners. The aim of this survey was to explore practitioners understanding and treatment of women with CPP, and how they integrate their management and care into the health care system.

Method

An online cross-sectional survey of registered TCM practitioners in Australia and New Zealand between May and October 2018. Survey domains included treatment characteristics (e.g. frequency), evaluation of treatment efficacy, referral networks, and sources of information that informed clinical decision making.

Results

One hundred and twenty-two registered TCM practitioners responded to this survey, 91.7% reported regular treatment of women with CPP. Treatment decisions were most-often guided by a combination of biomedical and TCM diagnosis (77.6%), and once per week was the most common treatment frequency (66.7%) for acupuncture. Meditation (63.7%) and dietary changes (57.8%) were other commonly used approaches to management.

The effectiveness of treatment was assessed using multiple approaches, most commonly pain scales, (such as the numeric rating scale) and any change in use of analgesic medications. Limitations to TCM treatment were reported by over three quarters (83.7%) of practitioners, most commonly due to cost (56.5%) and inconvenience (40.2%) rather than safety or lack of efficacy. Sources informing practice were most often Integration within the wider healthcare system was common with over two thirds (67.9%) receiving referrals from health care providers.

Conclusion

TCM practitioners seeing women with various CPP symptoms, commonly incorporate both traditional and modern diagnostic methods to inform their treatment plan, monitor treatment progress using commonly accepted approaches and measures and often as a part of multidisciplinary healthcare for women with CPP.
What does engagement mean to participants in longitudinal cohort studies? A qualitative study
Authors: Ochieng Cynthia A. , Minion Joel T. , Turner Andrew , Blell Mwenza , Murtagh Madeleine J.
Published: June 2021

Background

Engagement is important within cohort studies for a number of reasons. It is argued that engaging participants within the studies they are involved in may promote their recruitment and retention within the studies. Participant input can also improve study designs, make them more acceptable for uptake by participants and aid in contextualising research communication to participants. Ultimately it is also argued that engagement needs to provide an avenue for participants to feedback to the cohort study and that this is an ethical imperative. This study sought to explore the participants’ experiences and thoughts of their engagement with their birth cohort study.

Methods

Participants were recruited from the Children of the 90s (CO90s) study. Qualitative semi-structured interviews were conducted with 42 participants. The interviews were transcribed verbatim, and uploaded onto Nvivo software. They were then analysed via thematic analysis with a constant comparison technique.

Results

Participants’ experiences of their engagement with CO90s were broadly based on three aspects: communication they received from CO90s, experiences of ethical conduct from CO90s and receiving rewards from CO90s. The communication received from CO90s, ranged from newsletters explaining study findings and future studies, to more personal forms like annual greeting cards posted to each participant. Ethical conduct from CO90s mainly involved participants understanding that CO90s would keep their information confidential, that it was only involved in ‘good’ ethical research and their expectation that CO90s would always prioritise participant welfare. Some of the gifts participants said they received at CO90s included toys, shopping vouchers, results from clinical tests, and time off from school to attend data collection (Focus) days. Participants also described a temporality in their engagement with CO90s and the subsequent trust they had developed for the cohort study.

Conclusion

The experiences of engagement described by participants were theorized as being based on reciprocity which was sometimes overt and other times more nuanced. We further provide empirical evidence of participants’ expectation for a reciprocal interaction with their cohort study while highlighting the trust that such an interaction fosters. Our study therefore provides key insights for other cohort studies on what participants value in their interactions with their cohort studies.
Prognostic significance of CD163+ tumor-associated macrophages in colorectal cancer
Authors: Xue Tao , Yan Kejing , Cai Yiqi , Sun Jiancheng , Chen Zhejing , Chen Xiaolei , Wu Wenyi
Published: June 2021

Background

This study aimed to explore the prognostic significance of tumor-associated macrophage (TAM) infiltration in colorectal cancer (CRC) patients.

Methods

Tissue microarray and immunohistochemistry were used to detect the infiltration of CD163+ TAMs in 209 CRC samples, and the Kaplan–Meier method was used for survival analysis. Cox proportional hazards analysis was used for univariate analysis and multivariate analysis of clinically relevant confounders.

Results

The samples were divided into low-level (n = 105) and high-level infiltration groups (n = 104) by the median number of CD163+ TAMs detected. The overall survival (OS) and disease-free survival (DFS) of CRC patients in the low-level CD163+ TAM infiltration group were longer than those in the high-level CD163+ TAM infiltration group (P < 0.001). Infiltration of CD163+ TAMs in CRC tissues was a negative prognostic factor for CRC patients. Risks of death and disease recurrence for CRC patients in the low-level CD163+ TAM infiltration group were lower than those in the high-level CD163+ TAM infiltration group (HROS = 0.183, 95% CI 0.052–0.647, P = 0.008; HRDFS = 0.191, 95% CI 0.078–0.470, P = 0.000).

Conclusions

The infiltration of CD163+ TAMs in CRC tissue is an independent adverse factor for the prognosis of CRC patients. High-level infiltration of CD163+ TAMs is associated with shorter OS and DFS.
Time-course transcriptome analysis of host cell response to poxvirus infection using a dual long-read sequencing approach
Authors: Maróti Zoltán , Tombácz Dóra , Prazsák István , Moldován Norbert , Csabai Zsolt , Torma Gábor , Balázs Zsolt , Kalmár Tibor , Dénes Béla , Snyder Michael , Boldogkői Zsolt
Published: June 2021

Objective

In this study, we applied two long-read sequencing (LRS) approaches, including single-molecule real-time and nanopore-based sequencing methods to investigate the time-lapse transcriptome patterns of host gene expression as a response to Vaccinia virus infection. Transcriptomes determined using short-read sequencing approaches are incomplete because these platforms are inefficient or fail to distinguish between polycistronic RNAs, transcript isoforms, transcriptional start sites, as well as transcriptional readthroughs and overlaps. Long-read sequencing is able to read full-length nucleic acids and can therefore be used to assemble complete transcriptome atlases.

Results

In this work, we identified a number of novel transcripts and transcript isoforms of Chlorocebus sabaeus. Additionally, analysis of the most abundant 768 host transcripts revealed a significant overrepresentation of the class of genes in the “regulation of signaling receptor activity” Gene Ontology annotation as a result of viral infection.
The epigenetic etiology of cardiovascular disease in a longitudinal Swedish twin study
Authors: Qin Xueying , Karlsson Ida K. , Wang Yunzhang , Li Xia , Pedersen Nancy , Reynolds Chandra A. , Hägg Sara
Published: June 2021

Background

Studies on DNA methylation have the potential to discover mechanisms of cardiovascular disease (CVD) risk. However, the role of DNA methylation in CVD etiology remains unclear.

Results

We performed an epigenome-wide association study (EWAS) on CVD in a longitudinal sample of Swedish twins (535 individuals). We selected CpGs reaching the Bonferroni-corrected significance level (2 $$\times$$
×
 10–7) or the top-ranked 20 CpGs with the lowest P values if they did not reach this significance level in EWAS analysis associated with non-stroke CVD, overall stroke, and ischemic stroke, respectively. We further applied a bivariate autoregressive latent trajectory model with structured residuals (ALT-SR) to evaluate the cross-lagged effect between DNA methylation of these CpGs and cardiometabolic traits (blood lipids, blood pressure, and body mass index). Furthermore, mediation analysis was performed to evaluate whether the cross-lagged effects had causal impacts on CVD. In the EWAS models, none of the CpGs we selected reached the Bonferroni-corrected significance level. The ALT-SR model showed that DNA methylation levels were more likely to predict the subsequent level of cardiometabolic traits rather than the other way around (numbers of significant cross-lagged paths of methylation → trait/trait → methylation were 84/4, 45/6, 66/1 for the identified three CpG sets, respectively). Finally, we demonstrated significant indirect effects from DNA methylation on CVD mediated by cardiometabolic traits.

Conclusions

We present evidence for a directional association from DNA methylation on cardiometabolic traits and CVD, rather than the opposite, highlighting the role of epigenetics in CVD development.
A comparison of zero-inflated and hurdle models for modeling zero-inflated count data
Authors: Feng Cindy Xin
Published: June 2021

Counts data with excessive zeros are frequently encountered in practice. For example, the number of health services visits often includes many zeros representing the patients with no utilization during a follow-up time. A common feature of this type of data is that the count measure tends to have excessive zero beyond a common count distribution can accommodate, such as Poisson or negative binomial. Zero-inflated or hurdle models are often used to fit such data. Despite the increasing popularity of ZI and hurdle models, there is still a lack of investigation of the fundamental differences between these two types of models. In this article, we reviewed the zero-inflated and hurdle models and highlighted their differences in terms of their data generating processes. We also conducted simulation studies to evaluate the performances of both types of models. The final choice of regression model should be made after a careful assessment of goodness of fit and should be tailored to a particular data in question.
Evaluation of pharmacy-led weight management service to minimise the risk of cardiovascular disease
Authors: Peletidi Aliki , Kayyali Reem
Published: June 2021

Aims

The primary aim of the programme was a minimum of a 5% weight reduction of the initial weight, while the secondary outcomes were a reduction in participants’ body mass index (BMI), waist circumference (WC), blood pressure (BP), AUDIT-C score and an increase in the Mediterranean diet (MD) score and an improvement in physical activity levels.

Methods

This 'before and after' study was a 10-week weight management (WM) programme and it was developed and delivered in community pharmacies in Patras chosen for convenience, thus consisting the first service of its type in Greece. The sample size was calculated (n = 96) based on the mean BMI for a Greek male and female individual, and the standard deviation (SD) of weight at baseline of 14 kg.

Results

Nearly every participant enrolled in the 20 participating pharmacies, 97.4% (n = 114/117), achieved the programme’s aim, losing at least 5% of their initial weight. The mean percentage of total weight loss of the 117 participants at the 10th week was 8.97% (SD 2.65), and thet-test showed statistically significant results (P-value < 0.001; 95% CI [8.48, 9.45]). A significant reduction in the waist-to-height ratio (WHtR) was observed in both male (P-value = 0.004) and female (P-value < 0.001) participants. The participants’ BP and AUDIT-C score and physical activity levels significantly improved (P-value < 0.001), as well as their MD score.

Conclusion

This study provides the first evidence that Greek pharmacists have the potential to play an important role within primary healthcare and that after training they are able to provide public health services for both the public’s benefit and their clinical role enhancement.
Root extracts of Anacardium occidentale reduce hyperglycemia and oxidative stress in vitro
Authors: Archana TM , Soumya K , James Jesna , Sudhakaran Sudheesh
Published: June 2021

Background

Hyperglycemia is the hallmark of diabetes, and the associated oxidative stress is a major concern that invites an array of diabetic complications. The traditional practices of medicare are of great, current interest due to the high cost and side effects of conventional diabetic medications. The present in vitro study focuses on evaluating the potential of various A. occidentale root extracts for their antihyperglycemic and antioxidant potentials.

Materials and methods

The four different solvent extracts petroleum ether (PEAO), chloroform (CHAO), ethyl acetate (EAAO), and 80 % methanol (80 % MAO) of A. occidentale roots were evaluated for their total phenolic, flavonoid, and antioxidant capacity. Using MIN6 pancreatic β-cells, the cytotoxicity of the extracts was evaluated by MTT assay and the antidiabetic potential by quantifying the insulin levels by ELISA at a higher concentration of glucose. The effect of 80 % MAO on INS gene expression was determined by qRT PCR analysis.

Results

Among the four different solvent extracts of A. occidentale roots, 80 % MAO showed the highest concentration of phenolics (437.33 ± 0.03 µg GAE/mg), CHAO to be a rich source of flavonoids (46.04 ± 0.1 µg QE/mg) and with the highest total antioxidant capacity (1865.33 ± 0.09 µg AAE/ mg). Evaluation of the free radical scavenging and reducing properties of the extracts indicated 80 % MAO to exhibit the highest activity. The MTT assay revealed the least cytotoxicity of all four extracts. 80 % MAO enhanced INS up-regulation as well as insulin secretion even under high glucose concentration (27mM).

Conclusions

The present study demonstrated that the A. occidentale root extracts have effective antihyperglycemic and antioxidative properties, together with the potential of normalizing the insulin secretory system of β-cells. Above mentioned properties have to be studied further by identifying the active principles of A. occidentale root extracts and in vivo effects. The prospect of the present study is identifying drug leads for better management of diabetes from the A. occidentale root extracts.

Graphical abstract
Frequent burning in chir pine forests, Uttarakhand, India
Authors: Fulé Peter Z. , Garkoti Satish C. , Semwal Rajeev L.
Published: June 2021

Background

Subtropical coniferous forests of the lesser Himalaya provide critical ecosystem services but fire regimes have received limited scientific attention. We reconstructed fire regimes using tree-ring methods in a chir pine (Pinus roxburghii Sarg.) forest of Uttarakhand, India. We cross-dated tree-ring samples with fire scars from 36 trees at three sites near rural villages between 1535 and 1848 m elevation.

Results

Fires were highly frequent (mean fire intervals all <6 yr) but of low severity, so most mature trees of this thick-barked species survived numerous burns. Fire scars occurred primarily in the dormant period to the middle of early wood formation in tree-rings, consistent with fire season records. Despite the high fire frequency, fires were mostly asynchronous among the three sites, indicating a bottom-up pattern of local ignitions. We observed that resin tapping of the pines interacted with surface fire by allowing fire to burn into the wood of some tapped trees and weaken their structural integrity to the point of breakage.

Conclusions

Ongoing frequent surface fire regimes linked to human land use are prominent disturbance factors in chir pine forests. Given that these forests support substantial human populations and form part of the watershed for many more people, the effects of anthropogenic fire and interactions with resin-tapping merit further investigation at landscape to regional scales. We suggest developing a research network in Himalayan forests as well as more broadly across southeast Asian pine forests to track interacting disturbances and their ecological and social implications.
Visualizing risk factors of dementia from scholarly literature using knowledge maps and next-generation data models
Authors: Fahd Kiran , Venkatraman Sitalakshmi
Published: June 2021

Scholarly communication of knowledge is predominantly document-based in digital repositories, and researchers find it tedious to automatically capture and process the semantics among related articles. Despite the present digital era of big data, there is a lack of visual representations of the knowledge present in scholarly articles, and a time-saving approach for a literature search and visual navigation is warranted. The majority of knowledge display tools cannot cope with current big data trends and pose limitations in meeting the requirements of automatic knowledge representation, storage, and dynamic visualization. To address this limitation, the main aim of this paper is to model the visualization of unstructured data and explore the feasibility of achieving visual navigation for researchers to gain insight into the knowledge hidden in scientific articles of digital repositories. Contemporary topics of research and practice, including modifiable risk factors leading to a dramatic increase in Alzheimer’s disease and other forms of dementia, warrant deeper insight into the evidence-based knowledge available in the literature. The goal is to provide researchers with a visual-based easy traversal through a digital repository of research articles. This paper takes the first step in proposing a novel integrated model using knowledge maps and next-generation graph datastores to achieve a semantic visualization with domain-specific knowledge, such as dementia risk factors. The model facilitates a deep conceptual understanding of the literature by automatically establishing visual relationships among the extracted knowledge from the big data resources of research articles. It also serves as an automated tool for a visual navigation through the knowledge repository for faster identification of dementia risk factors reported in scholarly articles. Further, it facilitates a semantic visualization and domain-specific knowledge discovery from a large digital repository and their associations. In this study, the implementation of the proposed model in the Neo4j graph data repository, along with the results achieved, is presented as a proof of concept. Using scholarly research articles on dementia risk factors as a case study, automatic knowledge extraction, storage, intelligent search, and visual navigation are illustrated. The implementation of contextual knowledge and its relationship for a visual exploration by researchers show promising results in the knowledge discovery of dementia risk factors. Overall, this study demonstrates the significance of a semantic visualization with the effective use of knowledge maps and paves the way for extending visual modeling capabilities in the future.
Study of HOTAIR LncRNA in AML patients in context to FLT3-ITD and NPM1 mutations status
Authors: Salah Mona , Zawam Hamdy , Fouad Neven Bahaa , Soliman Nohair , Maksoud Fatma Abdel Wahab Abdel
Published: June 2021

Background

Long non-coding RNAs (LncRNAs) have recently been considered promising biomarkers for oncogenesis due to their epigenetic regulatory effects. HOTAIR is one of the oncogenic LncRNAs that was previously studied in different non-hematological malignancies. The current study set out to detect the expression level of HOTAIR LncRNA in AML patients concerning their clinical characteristics, laboratory data, FLT3-ITD, and NPM1 mutations, as well as treatment outcome. This study included quantitative detection of HOTAIR gene expression in 47 cases of AML using quantitative reverse transcription polymerase chain reaction, as well as NPM1 and FLT3-ITD genotyping.

Results

The HOTAIR expression was significantly higher in AML patients 6.87 (0.001) than in normal controls 1.66 (0.004–6.82) (p 0.007). The HOTAIR expression level was affected by chemotherapy, and it was correlated to hemoglobin level (p 0.001), age, total leukocytic count (p 0.022), and NPM1 mutation (p 0.017). HOTAIR gene expression level showed a correlation to relapse-free survival in the study group (p 0.04).

Conclusion

HOTAIR is overexpressed in patients with acute myeloid leukemia (AML). HOTAIR pre-treatment and post-chemotherapy gene expression levels can predict chemosensitivity and relapse.
Genomic Classification and Clinical Outcome in Rhabdomyosarcoma: A Report From an International Consortium
Authors: Shern Jack F. , Selfe Joanna , Izquierdo Elisa , Patidar Rajesh , Chou Hsien-Chao , Song Young K. , Yohe Marielle E. , Sindiri Sivasish , Wei Jun , Wen Xinyu , Rudzinski Erin R. , Barkauskas Donald A. , Lo Tammy , Hall David , Linardic Corinne M. , Hughes Debbie , Jamal Sabri , Jenney Meriel , Chisholm Julia , Brown Rebecca , Jones Kristine , Hicks Belynda , Angelini Paola , George Sally , Chesler Louis , Hubank Michael , Kelsey Anna , Gatz Susanne A. , Skapek Stephen X. , Hawkins Douglas S. , Shipley Janet M. , Khan Javed
Published: June 2021

PURPOSE

Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Despite aggressive therapy, the 5-year survival rate for patients with metastatic or recurrent disease remains poor, and beyond PAX-FOXO1 fusion status, no genomic markers are available for risk stratification. We present an international consortium study designed to determine the incidence of driver mutations and their association with clinical outcome.

PATIENTS AND METHODS

Tumor samples collected from patients enrolled on Children's Oncology Group trials (1998-2017) and UK patients enrolled on malignant mesenchymal tumor and RMS2005 (1995-2016) trials were subjected to custom-capture sequencing. Mutations, indels, gene deletions, and amplifications were identified, and survival analysis was performed.

RESULTS

DNA from 641 patients was suitable for analyses. A median of one mutation was found per tumor. In FOXO1 fusion-negative cases, mutation of any RAS pathway member was found in > 50% of cases, and 21% had no putative driver mutation identified. BCOR (15%), NF1 (15%), and TP53 (13%) mutations were found at a higher incidence than previously reported and TP53 mutations were associated with worse outcomes in both fusion-negative and FOXO1 fusion-positive cases. Interestingly, mutations in RAS isoforms predominated in infants < 1 year (64% of cases). Mutation of MYOD1 was associated with histologic patterns beyond those previously described, older age, head and neck primary site, and a dismal survival. Finally, we provide a searchable companion database ( ClinOmics ), containing all genomic variants, and clinical annotation including survival data.

CONCLUSION

This is the largest genomic characterization of clinically annotated rhabdomyosarcoma tumors to date and provides prognostic genetic features that refine risk stratification and will be incorporated into prospective trials.