bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between premature ovarian insufficiency and gut microbiota
Authors: Wu Jiaman , Zhuo Yuanyuan , Liu Yulei , Chen Yan , Ning Yan , Yao Jilong 
Published: June 2021

Abstract
Background
Premature ovarian insufficiency (POI) is characterized by impairment of ovarian function on a continuum before the age of 40 years. POI is affected by multiple factors. Considering new insights from recent gut microbiome studies, this study aimed to investigate the relationship between gut microbial community structure and POI.

Methods
Subjects were recruited at the Shenzhen Maternity & Child Healthcare Hospital. Fecal microbial community profiles of healthy women (n = 18), women with POI (n = 35) were analyzed using 16S rRNA gene sequencing based on Illumina NovaSeq platform.

Results
Compared to the controls, the serum levels of FSH, LH, T and FSH/LH ratio significantly increased in women with POI, whereas E2 and AMH decreased significantly. Higher weighted UniFrac value was observed in POI women compared with healthy women. Phylum Firmicutes, genera Bulleidia and Faecalibacterium were more abundant in healthy women, while phylum Bacteroidetes, genera Butyricimonas, Dorea, Lachnobacterium and Sutterella enriched significantly in women with POI. Moreover, these alterations of the gut microbiome in women with POI were closely related to FSH, LH, E2, AMH level and FSH/LH ratio.

Conclusions
Women with POI had altered microbial profiles in their gut microbiome, which were associated with serum hormones levels. These results will shed a new light on the pathogenesis and treatment for POI.
Differential chromatin accessibility landscape of gain-of-function mutant p53 tumours
Authors: Dhaka Bhavya , Sabarinathan Radhakrishnan 
Published: June 2021

Abstract
Background
Mutations in TP53 not only affect its tumour suppressor activity but also exerts oncogenic gain-of-function activity. While the genome-wide mutant p53 binding sites have been identified in cancer cell lines, the chromatin accessibility landscape driven by mutant p53 in primary tumours is unknown. Here, we leveraged the chromatin accessibility data of primary tumours from The Cancer Genome Atlas (TCGA) to identify differentially accessible regions in mutant p53 tumours compared to wild-type p53 tumours, especially in breast and colon cancers.

Results
We identified 1587 lost and 984 gained accessible chromatin regions in breast, and 1143 lost and 640 gained regions in colon cancers. However, only less than half of those regions in both cancer types contain sequence motifs for wild-type or mutant p53 binding. Whereas, the remaining showed enrichment for master transcriptional regulators, such as FOX-Family TFs and NF-kB in lost and SMAD and KLF TFs in gained regions of breast. In colon, ATF3 and FOS/JUN TFs were enriched in lost, and CDX family TFs and HNF4A in gained regions. By integrating the gene expression data, we identified known and novel target genes regulated by the mutant p53.

Conclusion
This study reveals the direct and indirect mechanisms by which gain-of-function mutant p53 targets the chromatin and subsequent gene expression patterns in a tumour-type specific manner. This furthers our understanding of the impact of mutant p53 in cancer development.
Significance of liver resection for intermediate stage hepatocellular carcinoma according to subclassification
Authors: Yamamoto Masateru , Kobayashi Tsuyoshi , Hashimoto Masakazu , Kuroda Shintaro , Kawaoka Tomokazu , Aikata Hiroshi , Chayama Kazuaki , Ohdan Hideki 
Published: June 2021

Abstract
Background
Patients diagnosed with Barcelona Clinic Liver Cancer (BCLC) intermediate stage hepatocellular carcinoma (HCC) encompass a broad clinical population. Kinki criteria subclassifications have been proposed to better predict prognoses and determine appropriate treatment strategies for these patients. This study validated the prognostic significance within the Kinki criteria substages and analyzed the role of liver resection in patients with intermediate stage HCC.

Methods
Patients with intermediate stage HCC (n = 378) were retrospectively subclassified according to the Kinki criteria (B1, n = 123; B2, n = 225; and B3, n = 30). We analyzed the overall survival (OS) and treatment methods.

Results
The OS was significantly different between adjacent substages. Patients in substage B1 who underwent liver resection had a significantly better prognosis than those who did not, even after propensity score matching (PSM). Patients in substage B2 who underwent liver resection had a significantly better prognosis than those who did not; however, there was no difference after PSM. There was no difference in prognosis based on treatments among patients in substage B3.

Conclusions
The Kinki criteria clearly stratify patients with intermediate stage HCC by prognosis. For substage B1 HCC patients, liver resection provides a better prognosis than other treatment modalities. In patients with substage B2 and B3, an alternative approach is required.
Long-term results of topical 0.02% tacrolimus ointment for refractory ocular surface inflammation in pediatric patients
Authors: Koh Kyungmin , Jun Ikhyun , Kim Tae-im , Kim Eung Kweon , Seo Kyoung Yul 
Published: June 2021

Abstract
Background
No studies have been reported on the efficacy and safety of long-term (≥12 months) use of topical tacrolimus for refractory ocular surface inflammation in pediatric patients.

Methods
Medical records of pediatric patients who were prescribed topical 0.02% tacrolimus ointment for refractory ocular surface inflammation between January of 2010 and March of 2018 were reviewed retrospectively. Changes in ocular surface signs during slit-lamp examination, clinical symptoms and concurrent steroid use were graded with a scoring system. The presence of side effects was also assessed. The changes in disease severity and patient symptoms were compared between baseline and after the treatment.

Results
Among 72 patients (55% males, mean age 10.8 ± 3.9 years, range 3 to 17 years), 25 patients (48% males, mean age 11.4 ± 3.9 years) fully recovered, resulting in discontinuance of the ointment treatment before 12 months. Six patients experienced intolerable burning sensation, which required treatment cessation. Cessation days of those who quit were 1,5,14,20,26, and 35 days. Seven patients were lost during follow-up. Thirty-four patients (56% males, mean age 11.2 ± 4.2 years, range 3 to 17 years) were treated with tacrolimus ointment for over 12 months (average 23.1 ± 19.1 months, range 12 to 98 months). During the follow-up period, all patients showed improved clinical signs and symptoms, and no adverse reaction was noted.

Conclusions
Long-term maintenance of topical tacrolimus 0.02% ointment is safe and effective in improving refractory ocular surface inflammation in pediatric patients.
Nonspecific orbital inflammation and thyroid eye disease, a rare comorbidity: report of two cases and review of literature
Authors: Eshraghi Bahram , Dehghan Amin , Javadi Niloofar , Fazel Mohammadreza 
Published: June 2021

Abstract
Background
To present the very rare comorbidity of developing non-specific orbital inflammation (NSOI) in two patients with histories of definite thyroid eye disease (TED).

Case presentation
Both patients complained of new-onset progressive proptosis although their thyroid disease was controlled and computed tomography scan revealed an intraorbital inflammatory mass. The pathological assessment indicated that both patients had developed fibrosing NSOI. Therefore, intravenous corticosteroids were administered. The mass regressed and the amount of proptosis was decreased in both patients.

Conclusions
We reviewed all related cases in the literature and extracted their clinical and radiological characteristics for this paper. Ophthalmologists should consider TED and NSOI in patients with a new-onset complaint of proptosis. Despite rare comorbidity of TED and NSOI, it should be considered especially in patients with refractory proptosis, and lead to its further evaluation and prompt management.
A pilot study to evaluate the role of circulation CD4+ CCR6+ CRTh2+ cell in predicting risk of asthma in wheezing children
Authors: Li Jingyang , Wu Jinhong , Liu Haipei , Hua Li , Liu Quanhua , Fang Dingzhu , Chen Yi , Ji Ruoxu , Zhang Jianhua , Zhong Wenwei 
Published: June 2021

Abstract
Background
Wheezing is common in younger children and often related to viral infection. It is lack of reliable indicators for asthma prediction.

Objective
To evaluate the relationship between circulation CD4+CCR6+CRTh2+ memory Th2 cells and asthma diagnosis in wheezing children.

Methods
A prospective study was performed in children under 5 years old presented with wheezing or at last one episode of documented wheezing history. After inclusion, the level of serum allergen-specific serum IgE (sIgE) and circulating CD4+CCR6+CRTh2+cells were detected. The patients’ personal and family histories of allergic disease were acquired by questionnaire. The children were followed up over 2 years. Diagnosis of asthma was assessed at the end follow-up. The risk factors in predicting asthma diagnosis were evaluated.

Results
A total of 43 children completed follow-up. Higher wheezing frequency were found in children with asthma diagnosis. The mean of circulating CD4+CCR6+CRTh2+cells in children diagnosed with or without asthma was 1.6 %±0.8 and 0.8 %±0.6 %, respectively, and was significantly higher in children diagnosed with asthma (p < 0.01). There was no significant difference between children with and without allergic diseases history or family allergic diseases in level of circulating CD4+CCR6+CRTh2+ cells. Logistic regression analysis indicated that circulating CD4+CCR6+CRTh2+ cells (EXP, 8.986; 95 % CI,1.886–42.816) and wheezing frequency(EXP, 0.127; 95 % CI, 0.023–0.703)were high risk factors for asthma.

Conclusions
Our exploratory study shown that circulating CD4+CCR6+CRTh2+ memory Th2 cells increased in asthma diagnosed children and it was a high-risk factor for asthma. Detection of this type of cells could be helpful in predicting the risk of asthma in wheezing children.
Cervical cancer screening prevalence and its correlates in Cameroon: secondary data analysis of the 2018 demographic and health surveys
Authors: Okyere Joshua , Duodu Precious Adade , Aduse-Poku Livingstone , Agbadi Pascal , Nutor Jerry John 
Published: June 2021

AbstractBackgroundCervical cancer, although preventable, is the fourth most common cancer among women globally, and the second most common and deadliest gynaecological cancer in low-and-middle-income countries. Screening is key to the prevention and early detection of the disease for treatment. A few studies estimated the prevalence of cervical cancer screening and its correlates in Cameroon but relied on data that were limited to certain regions of the country. Therefore, this study sought to examine the prevalence and correlates of cervical cancer screening among Cameroonian women using current data that is nationally representative of reproductive-age women.MethodsWe used secondary data from the 2018 Cameroon Demographic and Health Survey. Summary statistics were used for the sample description. We employed the Firth logistic regression using the “firthlogit” command in STATA-14 to perform the bivariate analyses between the outcome variable and each of the explanatory variables. Given that all the explanatory variables were statistically significant correlates, they were all adjusted for in a multivariable analysis. All analyses were performed in STATA version 14.ResultsThe proportion of Cameroonian women who have ever screened for cervical cancer continue to remain low at approximately 4%. In the adjusted model, women with the following sociodemographic characteristics have a higher likelihood of undergoing cervical cancer screening: ever undergone HIV screening (AOR = 4.446, 95% CI: 2.475, 7.986), being 24–34 years (AOR = 2.233, 95% CI: 1.606, 3.103) or 35–44 years (AOR = 4.008, 95% CI: 2.840, 5.657) or at least 45 years old (AOR = 5.895, 95% CI: 3.957, 8.784), having attained a post-secondary education (AOR = 1.849, 95% CI: 1.032, 3.315), currently (AOR = 1.551, 95% CI: 1.177, 2.043) or previously married (AOR = 1.572, 95% CI: 1.073, 2.302), dwelling in the richest household (AOR = 4.139, 95% CI: 1.769, 9.682), and residing in an urban area (AOR = 1.403, 95% CI: 1.004,1.960). Except for the North-West region, residing in some five regions, compared to Yaounde, was negatively associated with cervical cancer screening.ConclusionCervical cancer screening programs and policies should target Cameroonian women who are younger, less educated, and those in poor households and rural areas.
How does social support affect public service motivation of healthcare workers in China: the mediating effect of job stress
Authors: Deng Jianwei , Liu Jiahao , Guo Yuangeng , Gao Yongchuang , Wu Zhennan , Yang Tianan 
Published: June 2021

Abstract
Background
This study aimed to examine relations between social support, job stress, and public service motivation (PSM), also assessed how social support and job stress affect PSM in China based on the job demands-resources (JD-R) theory.

Methods
The survey investigated a sample of 973 healthcare workers employed in public hospitals in Beijing, Xiamen, and Guangzhou in 2017 (including doctors, nurses, medical technicians, and administrators). Correlation analysis and Structural equation modeling (SEM) were used.

Results
Challenge stress and hindrance stress were directly negatively associated with PSM. Supervisor support was significantly positively associated with PSM, and the path from coworker support to PSM was significant. Supervisor support was significantly negatively associated with hindrance stress, and coworker support was significantly negatively associated with challenge stress. Hindrance stress and challenge stress significantly mediated the relations between supervisor support and PSM, and between coworker support and PSM respectively. PSM might be raised by increasing supervisor support and coworker support and by limiting hindrance stress and challenge stress.

Conclusion
Our study suggests that administrators of public hospitals should be mindful of the intense job stress of healthcare workers and undertake interventions targeting challenge stress and hindrance stress. Also, public hospital administrators should encourage and assist supervisors in their leadership functions. Besides, administrators of public hospitals should emphasize coworker support and good employee relationships.
Factors associated with headache and neck pain among telecommuters – a five days follow-up
Authors: Houle Mariève , Lessard Arianne , Marineau-Bélanger Émile , Lardon Arnaud , Marchand Andrée-Anne , Descarreaux Martin , Abboud Jacques 
Published: June 2021

Abstract
Background
The current sanitary crisis brought on by the COVID-19 recently forced a large proportion of workers to adopt telecommuting with limited time to plan transition. Given that several work-related risk factors are associated with headache and neck pain, it seems important to determine those associated with headache and neck pain in telecommuters.
The main objective of this study was to identify which telecommuting and individual associated factors are related with headache and neck pain occurrence in telecommuters over a five days follow-up. The second objective was to evaluate the impact of wearing a headset on headache and neck pain intensity in telecommuters.

Methods
One hundred and sixty-two participants in telecommuting situation were recruited. Baseline assessment included sociodemographic data, headache and neck pain-related disability (6-item Headache Impact Test (HIT-6) and Neck Bournemouth Questionnaire (NBQ)), headache and neck pain frequency and intensity as well as questions about the wearing of a headset (headset wearing, headset type and headset wearing hours). A prospective data collection of headache, neck pain and headset wearing was conducted using daily e-mail over a 5-day follow-up. A stepwise multivariate regression model was performed to determine associated factors of headache or neck pain occurrence during the follow-up. A t-test was conducted to assess the impact of headset wearing on headache and neck pain intensity during the follow-up.

Results
Regarding headache, the stepwise multivariate regression model showed that the HIT-6 score was associated with future headache occurrence in telecommuters (OR (95% CI) = 1.094 (1.042–1.148); R2 = 0.094; p <  0.001). For neck pain, the stepwise multivariate regression showed that the NBQ score was related to future neck pain occurrence in telecommuters (OR (95% CI) = 1.182 (1.102–1.269); R2 = 0.182; p <  0.001). T-test showed no difference between participants that wore a headset and participant that did not wore a headset on mean headache (p = 0.94) and neck pain (p = 0.56) intensity during the five days follow-up.

Conclusion
Although several work-related risk factors are associated with headache and neck pain in workers, telecommuting did not present the same risks. Working set-up did not have a significant impact on headache and neck pain as headache-related disability was the only associated factor of future headache episodes and neck-pain related disability was the only associated factor of future neck pain episodes. Also, wearing a headset had no impact on headache and neck pain in telecommuters.
The perceptions and priorities of professionals in health and social welfare and city planning for creating a healthy living environment: a concept mapping study
Authors: Mourits Kristine , van der Velden Koos , Molleman Gerard 
Published: June 2021

Abstract
Background
It is helpful for collaboration if professionals from the field of health and social welfare and the field of city planning are aware of each other’s concepts of what a healthy living environment entails and what its components are. This study examined perceptions about creating a healthy living environment of professionals from these two fields, as well as the differences between them.

Methods
We recruited 95 professionals from Nijmegen, the Netherlands who worked in the fields of health, social welfare and city planning in governmental and non-governmental capacities. We used the concept mapping method to collect and analyse their thoughts on healthy living environments. Participants first submitted statements on this subject in a brainstorming session, using an online mapping tool. Then they sorted these statements and rated them on priorities and opportunities within urban planning processes.

Results
During the brainstorm, 43 professionals generated 136 statements. After the elimination of duplicates, 92 statements were individually sorted by 32 professionals. Concept mapping software was used to create an overall map, in which the statements were sorted into ten clusters. Each of these clusters represented one of the main features of a healthy living environments. After 36 participants rated these statements, it emerged that professionals from both fields agreed on priorities and opportunities for the clusters ‘Spatial quality’ and ‘Conducive to exercise’. Professionals also agreed on which three clusters had the fewest priorities and possibilities (‘Promotes personal wellbeing’, ‘Encourages healthy choices’, ‘Conducive to social connections’).

Conclusion
We found that professionals in health and social welfare and city planning have similar views concerning the most and least important features of a healthy living environment in urban planning process. This could indicate that the differences between the two fields may be more nuanced and specific than previously thought. This knowledge offers perspectives for professionals to strengthen their collaboration and to come to a joint result in urban planning projects.
Down-regulation of SNHG16 alleviates the acute lung injury in sepsis rats through miR-128-3p/HMGB3 axis
Authors: Sun Junli , Xin Keke , Leng Chenghui , Ge Jianlin 
Published: June 2021

Abstract
Background
Long noncoding RNAs contribute to various inflammatory diseases, including sepsis. We explore the role of small nucleolar RNA host gene 16 (SNHG16) in sepsis-mediated acute lung injury (ALI) and inflammation.

Methods
A sepsis-induced ALI rat model was constructed by the cecal ligation and perforation method. The profiles of SNHG16, miR-128-3p, and high-mobility group box 3 (HMGB3) were monitored by quantitative reverse transcription PCR and Western blot. The pathologic changes of lung tissues were evaluated by Hematoxylin–Eosin staining, immunohistochemistry, and dry and wet method. Meanwhile, the pro-inflammatory factors and proteins were determined by ELISA and Western blot. In contrast, a sepsis model in BEAS-2B was induced with lipopolysaccharide (LPS) to verify the effects of SNHG16/miR-128-3p/HMGB3 on lung epithelial cell viability and apoptosis.

Results
As a result, SNHG16 and HMGB3 were up-regulated, while miR-128-3p was down-regulated in sepsis-induced ALI both in vivo and in vitro. Inhibiting SNHG16 reduced the apoptosis and inflammation in the sepsis-induced ALI model. Overexpressing SNHG16 promoted LPS-mediated lung epithelial apoptosis and inhibited cell viability and inflammation, while miR-128-3p had the opposite effects. Mechanistically, SNHG16 targeted miR-128-3p and attenuated its expression, while miR-128-3p targeted the 3′ untranslated region of HMGB3.

Conclusions
Overall, down-regulating SNHG16 alleviated the sepsis-mediated ALI by regulating miR-128-3p/HMGB3.
EML4-ALK-mediated activation of the JAK2-STAT pathway is critical for non-small cell lung cancer transformation
Authors: Li Ying , Li Yongwen , Zhang Hongbing , Shi Ruifeng , Zhang Zihe , Liu Hongyu , Chen Jun 
Published: June 2021

Abstract
Background
The echinoderm microtubule-associated protein-like-4 anaplastic lymphoma kinase (EML4-ALK) fusion gene was identified in a subset of non-small cell lung cancer (NSCLC) patients. They responded positively to ALK inhibitors. This study aimed to characterize the mechanisms triggered by EML4-ALK to induce NSCLC transformation.

Methods
HEK293 and NIH3T3 cells were transfected with EML4-ALK variant 3 or pcDNA3.1-NC. H2228 cells were transfected with siRNA-EML4-ALK or siRNA-NC. Cell viability and proliferation were measured by the CCK-8 and EdU methods, respectively. Flow cytometry revealed apoptosis. Gene expression profiles were generated from a signaling pathway screen in EML4-ALK-regulated lung cancer cells and verified by qPCR and Western blotting. The co-immunoprecipitation and immunohistochemistry/ immunofluorescence determined the interaction and colocalization of JAK2-STAT pathway components with EML4-ALK.

Results
Microarray identified several genes involved in the JAK2-STAT pathway. JAK2 and STAT6 were constitutively phosphorylated in H2228 cells. EML4-ALK silencing downregulated phosphorylation of STAT6. Expression of EML4-ALK in HEK293 and NIH3T3 cells activated JAK2, STAT1, STAT3, STAT5, and STAT6. In EML4-ALK-transfected HEK293 cells and EML4-ALK-positive H2228 cells, activated STAT6 and JAK2 colocalized with ALK. STAT3 and STAT6 were phosphorylated and translocated to the nucleus of H2228 cells following IL4 or IL6 treatment. Apoptosis increased, while cell proliferation and DNA replication decreased in H2228 cells following EML4-ALK knockdown. In contrast, HEK293 cell viability increased following EML4-ALK overexpression, while H2228 cell viability significantly decreased after treatment with ALK or JAK-STAT pathway inhibitors.

Conclusions
Our data suggest that the aberrant expression of EML4-ALK leads to JAK2-STAT signaling pathway activation, which is essential for the development of non-small cell lung cancer.