bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular basis of high temperature-induced bolting in lettuce revealed by multi-omics analysis
Authors: Hao Jinghong , Yang Junwei , Liu Xiaofeng , Pan Gaoyang , Li Yunfeng , Zhang Xiaolan , Han Yingyan , Fan Shuangxi , Zhou Zhaoyang 
Published: August 2022

Abstract
Background
High temperature induces early bolting in lettuce (Lactuca sativa L.), which affects both quality and production. However, the molecular mechanism underlying high temperature-induced bolting is still limited.

Results
We performed systematical analysis of morphology, transcriptome, miRNAs and methylome in lettuce under high temperature treatment. Through a comparison of RNA-Seq data between the control and the high temperature treated lettuces at different time points totally identified 2944 up-regulated genes and 2203 down-regulated genes, which cover three floral pathways including photoperiod, age and gibberellin (GA) pathways. Genome wide analysis of miRNAs and methylome during high temperature treatment indicated miRNAs and DNA methylation might play a role controlling gene expression during high temperature-induced bolting. miRNA targets included some protein kinase family proteins, which potentially play crucial roles in this process.

Conclusions
Together, our results propose a possible regulation network involved in high temperature-induced bolting.
Evaluating the impact of calibration of patient-reported outcomes measures on results from randomized clinical trials: a simulation study based on Rasch measurement theory
Authors: Loubert Angély , Regnault Antoine , Sébille Véronique , Hardouin Jean-Benoit 
Published: August 2022

Abstract
Background
Meaningfully interpreting patient-reported outcomes (PRO) results from randomized clinical trials requires that the PRO scores obtained in the trial have the same meaning across patients and previous applications of the PRO instrument. Calibration of PRO instruments warrants this property. In the Rasch measurement theory (RMT) framework, calibration is performed by fixing the item parameter estimates when measuring the targeted concept for each individual of the trial. The item parameter estimates used for this purpose are typically obtained from a previous “calibration” study. But imposing this constraint on item parameters, instead of freely estimating them directly in the specific sample of the trial, may hamper the ability to detect a treatment effect. The objective of this simulation study was to explore the potential negative impact of calibration of PRO instruments that were developed using RMT on the comparison of results between treatment groups, using different analysis methods.

Methods
PRO results were simulated following a polytomous Rasch model, for a calibration and a trial sample. Scenarios included varying sample sizes, with instrument of varying number of items and modalities, and varying item parameters distributions. Different treatment effect sizes and distributions of the two patient samples were also explored. Cross-sectional comparison of treatment groups was performed using different methods based on a random effect Rasch model. Calibrated and non-calibrated approaches were compared based on type-I error, power, bias, and variance of the estimates for the difference between groups.

Results
There was no impact of the calibration approach on type-I error, power, bias, and dispersion of the estimates. Among other findings, mistargeting between the PRO instrument and patients from the trial sample (regarding the level of measured concept) resulted in a lower power and higher position bias than appropriate targeting.

Conclusions
Calibration does not compromise the ability to accurately assess a treatment effect using a PRO instrument developed within the RMT paradigm in randomized clinical trials. Thus, given its essential role in producing interpretable results, calibration should always be performed when using a PRO instrument developed using RMT as an endpoint in a randomized clinical trial.
Fertility intentions among young people in the era of China’s three–child policy: a national survey of university students
Authors: Zhang Chenyun , Wei Lingling , Zhu Yinyan , Teng Li , Zhang Wenchang , Xu Jia , Qin Mengqi , Jiang Na , Alias Haridah , Wong Li Ping 
Published: August 2022

Abstract
Background
This study aimed to assess the fertility intentions of young people after the announcement of the three–child policy in China and to determine whether knowledge about reproductive, maternal, newborn, and child health (RMNCH) services or support, childbearing- and childbirth-related anxiety, and parenthood–related anxiety influence fertility intentions.

Methods
A cross-sectional Internet-based survey was conducted on a nationwide sample of young people aged 18 to 28 years old in education institutions. Factors associated with fertility intentions were analysed using partial least squares structural equation modelling (PLS-SEM).

Results
Only 4.2% of males and 1.7% of females intended to have three children or more. On the whole, the majority (40.3%) reported the intention to have two children. The mean and standard deviation (SD) for the total knowledge RMNCH support and/or services knowledge score was 9.5 (SD ± 8.9), out of a possible score of 39. The median and interquartile range (IQR) of childbearing– and childbirth-related anxiety score was 8.0 (IQR = 6.0–9.0), out of a possible score of 10. The median and IQR of parenthood–related anxiety score among the males was 6.0 (IQR = 4.0–9.0) and for females was 7.0 (IQR = 5.0–9.0). Results from PLS-SEM revealed that a higher level of knowledge of RMNCH support and/or services is significantly associated with higher fertility intentions. Both childbearing- and childbirth-related anxiety and parenthood–related anxiety were inversely associated with fertility intentions.

Conclusion
Raising awareness about RMNCH supportive measures and easing birth- and parenting anxiety are imperative to enhance birth rates. Future policies should pay more attention to these determinants to achieve their intended goal of boosting population growth.
GPX4 suppresses ferroptosis to promote malignant progression of endometrial carcinoma via transcriptional activation by ELK1
Authors: Wei Sitian , Yu Zhicheng , Shi Rui , An Lanfen , Zhang Qi , Zhang Qian , Zhang Tangansu , Zhang Jun , Wang Hongbo 
Published: August 2022

Abstract
Background
Glutathione Peroxidase 4 (GPX4) is a key protein that inhibits ferroptosis. However, its biological regulation and mechanism in endometrial cancer (EC) have not been reported in detail.

Methods
The expression of GPX4 in EC tissues was determined by TCGA databases, qRT-PCR, Western blot, and immunohistochemistry (IHC). The effects of GPX4 on EC cell proliferation, migration, apoptosis, and tumorigenesis were studied in vivo and in vitro. In addition, ETS Transcription Factor ELK1 (ELK1) was identified by bioinformatics methods, dual-luciferase reporter assay, and chromatin immunoprecipitation (ChIP). Pearson correlation analysis was used to evaluate the association between ELK1 and GPX4 expression.

Results
The expression of GPX4 was significantly up-regulated in EC tissues and cell lines. Silencing GPX4 significantly inhibited the proliferation, migration ability, induced apoptosis, and arrested the cell cycle of Ishikawa and KLE cells. Knockdown of GPX4 accumulated intracellular ferrous iron and ROS, disrupted MMP, and increased MDA levels. The xenograft tumor model also showed that GPX4 knockdown markedly reduced tumor growth in mice. Mechanically, ELK1 could bind to the promoter of GPX4 to promote its transcription. In addition, the expression of ELK1 in EC was positively correlated with GPX4. Rescue experiments confirmed that GPX4 knockdown could reverse the strengthens of cell proliferation and migration ability and the lower level of Fe2+ and MDA caused by upregulating ELK1.

Conclusion
The results of the present study suggest that ELK1 / GPX4 axis plays an important role in the progress of EC by promoting the malignant biological behavior and inducing ferroptosis of EC cells, which provides evidence for investigating the potential therapeutic strategies of endometrial cancer.
Barriers to the management of sexual dysfunction among people with psychosis: analysis of qualitative data from the REMEDY trial
Authors: Thana Lavanya J. , O’Connell Lesley , Carne-Watson Alexandra , Shastri Abhishek , Saravanamuthu Arunan , Budhwani Natasha , Jayacodi Sandra , Leeson Verity C. , Munjiza Jasna , Pappa Sofia , Hughes Elizabeth , Reilly Joe , Crawford Mike J. 
Published: August 2022

Abstract
Background
More than half of people who use antipsychotic medication for psychosis report having sexual dysfunction. The REMEDY trial aimed to find out if switching antipsychotic medication provides an effective way to reduce sexual dysfunction among people with psychosis. We set out to recruit 216 participants over a two-year period, but recruitment was stopped after an extended 12-month pilot phase, during which we recruited only 10 participants. As part of a nested process evaluation, we conducted qualitative interviews with front-line clinicians to examine barriers to recruitment to the trial.

Methods
We developed a semi-structured interview schedule to explore staff views on factors that influenced whether they referred potential participants to the study. We interviewed a purposive sample of 51 staff from four National Health Service (NHS) Trusts in England, ensuring a range of different backgrounds, seniority, and levels of involvement in the trial. Audio recordings of interviews were transcribed for verbatim, and data were analysed using an inductive approach to thematic analysis.

Results
Nine interconnected themes were generated. Six themes concerned barriers to recruitment; including; prioritising patients’ mental stability, mutual discomfort and embarrassment about discussing a “taboo” subject, and concerns about unintended consequences of asking people with psychosis about their sexual functioning. Three themes, including the quality of treatment relationships and strategies for opening dialogue suggested ways to improve recognition of these “hidden” side effects.

Conclusion
The identification and management of sexual dysfunction among people with psychosis are not priorities for mental health services in England at this time. Many staff working in front-line services feel unprepared and uncomfortable asking people with psychosis about these problems. While greater use of screening tools may improve the identification of sexual dysfunction among people with psychosis, the evaluation and implementation of interventions to manage them will continue to be challenging unless NHS leaders and senior clinicians demonstrate greater commitment to changing current clinical practice.

Trial registration
Current Controlled Trials ISRCTN12307891.
Towards an integrated surveillance of zoonotic diseases in Burkina Faso: the case of anthrax
Authors: Nana Sougrenoma Désiré , Caffin Jean-Hugues , Duboz Raphaël , Antoine-Moussiaux Nicolas , Binot Aurélie , Diagbouga Potiandi Serge , Hendrikx Pascal , Bordier Marion 
Published: August 2022

AbstractBackgroundAnthrax is a zoonotic disease that causes frequent outbreaks in livestock and fatal human cases in Burkina Faso. Effective surveillance of this disease calls for the establishment of an integrated surveillance system, in line with the One Health concept. However, despite a strong technical and financial support from international partners, surveillance is still poorly conducted within an integrated approach. Based on stakeholder perspectives, the study has for objective to deepen our understanding of the anthrax surveillance system and to identify the obstacles and levers towards a more integrated approach to anthrax surveillance in Burkina Faso.MethodsThe data was collected from a literature review and interviews with surveillance stakeholders. We first conducted a qualitative descriptive analysis of the data to characterize the surveillance system (programmes, actors, collaboration). In a second step, we conducted a thematic analysis of the informants' discourse in order to identify what represents an obstacle or, conversely, a lever for a more integrated approach to anthrax surveillance.ResultsThe surveillance system of anthrax in Burkina Faso includes three programmes (in the livestock, wildlife and human sectors), which involves 30 actors. These sectoral programmes operate almost independently from one another, although some collaborations are existing for the governance and implementation of surveillance activities. Analysis of the discourse of key stakeholders led to the identification of four categories of factors that may influence the implementation of an integrated surveillance system in the country: knowledge; technical, organizational and social capacities; motivation; intersectoral governance.ConclusionsThis study highlights the difficulty of translating One Health governance to the national level and the need to better articulate the visions of all categories of stakeholders. This study also reveals the need to develop specific evaluation systems for integrated policies in order to provide credible evidence of their added value for a better management of zoonotic diseases. Finally, our study underlines the need to act upstream the emergence of zoonoses and allocate more resources to the prevention of zoonoses than to their control.
Women’s experience and perspectives toward genital cosmetic surgery in Erbil city/Iraq: a qualitative study
Authors: Piro Tiran Jamil , Saeed Awaz Aziz , Abdulla Warda Hassan , Safari Kolsoom 
Published: August 2022

Abstract
Background
Nowadays, Female Genital Cosmetic Surgery is quite prevalent, resulting in a wide range of medical and cultural implications. The majority of women who undergo this operation suffer from anxiety, depression, and other emotional symptoms. The present study was carried out in order to explore women’s perspective on and experience of genital cosmetic surgery given their special context and cultural aspects.

Methods
The qualitative study applying content analysis examined the experiences of nine women who received genital cosmetic surgery in Erbil, Kurdistan-Iraq, between 2021 and 2022. Each of the semi-in-depth face-to-face interviews lasted between 40 and 60 min and was conducted at the physician's clinics.

Results
Semi-structured interviews led to emergence of two main themes, namely “husband satisfaction” and “self-confidence”. Interpreting the participants’ stories resulted in some relevant subthemes and meaning units like “ugly appearance”, “anxiety related to husband undesirable intercourse”, and “dyspareunia”. Finally, the related conclusions of each theme were explored.

Conclusion
As suggested by the study findings, female genital cosmetic surgery improves the women’s body image and sexual function and the couples’ sexual satisfaction, especially that of husbands. Because of the people’s sociocultural aspects in Kurdistan region, their awareness of female sexual needs and marital relationship needs to be raised.
The effects of romosozumab combined with active vitamin D3 on fracture healing in ovariectomized rats
Authors: Takase Ryota , Tsubouchi Yuta , Otsu Takefumi , Kataoka Takashi , Iwasaki Tatsuya , Kataoka Masashi , Tsumura Hiroshi 
Published: August 2022

Abstract
Background
In this study, we investigated the potential acceleration of fracture healing and bone mineral density-increasing effects of romosozumab and active vitamin D3 combination therapy for fractures in ovariectomized rats.

Methods
Ovariectomy was performed on 40 24-week-old female Sprague–Dawley rats. After 8 weeks, the rats were subjected to periosteum removal and osteotomy of the femoral shaft followed by osteosynthesis with intramedullary nailing to create fracture models. The rats were then divided into four groups: C group (control), R group (receiving romosozumab at 25 mg/kg once a month via subcutaneous injection), VD group (receiving active vitamin D3 at 0.2 µg/kg twice a week via subcutaneous injection), and R + VD group. Further, 10 rats were included in a sham group. At 10 weeks after the intervention, both femurs were removed and blood samples were collected from all rats. Soft X-ray imaging was used to evaluate bone union, and microcomputed tomography (micro-CT) was used for bone morphometric evaluation. Toluidine blue staining was used for the histopathological evaluation of the undecalcified specimens, and bone turnover marker levels were measured using enzyme-linked immunosorbent assay.

Results
Bone morphometry analysis via micro-CT revealed increased mineral density of the trabecular bone in the R + VD group femurs, demonstrating the effectiveness of romosozumab plus active vitamin D3 combination therapy. However, there were no differences in bone union evaluated using soft X-ray imaging, indicating no acceleration of fracture healing.

Conclusions
Although romosozumab and active vitamin D3 combination therapy increased trabecular bone volume, there was no evidence on its ability to accelerate fracture healing.

Graphical abstract
Lysophosphatidic acid acyltransferase 2 and 5 commonly, but differently, promote seed oil accumulation in Brassica napus
Authors: Zhang Kai , He Jianjie , Yin Yongtai , Chen Kang , Deng Xiao , Yu Peng , Li Huaixin , Zhao Weiguo , Yan Shuxiang , Li Maoteng 
Published: August 2022

Abstract
Background
Increasing seed oil content (SOC) of Brassica napus has become one of the main plant breeding goals over the past decades. Lysophosphatidic acid acyltransferase (LPAT) performs an important molecular function by regulating the production of phosphatidic acid (PA), a key intermediate in the synthesis of membrane and storage lipids. However, the mechanism underlying the effect of LPAT on the SOC of B. napus remains unclear.

Results
In the present study, significant elevation of SOC was achieved by overexpressing BnLPAT2 and BnLPAT5 in B. napus. RNAi and CRISPR–Cas9 were also successfully used to knock down and knock out these two genes in B. napus where SOC significantly decreased. Meanwhile, we found an accumulation of lipid droplets and oil bodies in seeds of BnLPAT2 and BnLPAT5 overexpression lines, whereas an increase of sugar and protein in Bnlpat2 and Bnlpat5 mutant seeds. Sequential transcriptome analysis was further performed on the developing seeds of the BnLPAT2 and BnLPAT5 overexpression, knockdown, and knockout rapeseed lines. Most differentially expressed genes (DEGs) that were expressed in the middle and late stages of seed development were enriched in photosynthesis and lipid metabolism, respectively. The DEGs involved in fatty acid and lipid biosynthesis were active in the overexpression lines but were relatively inactive in the knockdown and knockout lines. Further analysis revealed that the biological pathways related to fatty acid/lipid anabolism and carbohydrate metabolism were specifically enriched in the BnLPAT2 overexpression lines.

Conclusions
BnLPAT2 and BnLPAT5 are essential for seed oil accumulation. BnLPAT2 preferentially promoted diacylglycerol synthesis to increase SOC, whereas BnLPAT5 tended to boost PA synthesis for membrane lipid generation. Taken together, BnLPAT2 and BnLPAT5 can jointly but differently promote seed oil accumulation in B. napus. This study provides new insights into the potential mechanisms governing the promotion of SOC by BnLPAT2 and BnLPAT5 in the seeds of B. napus.
Infusion of two-dose mesenchymal stem cells is more effective than a single dose in a dilated cardiomyopathy rat model by upregulating indoleamine 2,3-dioxygenase expression
Authors: Gong Chenyi , Chang Lei , Sun Xuan , Qi Yu , Huang Rong , Chen Ke , Wang Bin , Kang Lina , Wang Lian , Xu Biao 
Published: August 2022

Abstract
Background and aims
The therapeutic efficacy of single-dose mesenchymal stromal cell (MSC) therapy for heart failure (HF) remains inconsistent. This study aimed to investigate whether infusion with two-dose human umbilical cord MSC (hUCMSCs) could be therapeutically superior to single-dose therapy in a rat model of dilated cardiomyopathy (DCM) and explored the underlying mechanisms.

Methods
Male Sprague–Dawley rats were intraperitoneally injected with doxorubicin (DOX) to establish a DCM model and randomized to intravenously receive single-dose or two-dose hUCMSCs at an interval of 14 days. Their left ventricular (LV) systolic and diastolic functions were analyzed by echocardiography. The percentages of Th1, Th2, Th17, and Treg cells in the heart, spleen, lymph nodes, and peripheral blood and the levels of serum cytokines in individual rats were analyzed by flow cytometry and cytometric bead assay, respectively. The degrees of cardiac fibrosis and cardiomyocyte apoptosis were examined by histology. The importance of indoleamine 2,3-dioxygenase (IDO), an activator of Treg differentiation, in the therapeutic effect of hUCMSCs on inflammation and heart function of rats was determined after induction of IDO over-expression (IDO-OE) using IFN-γ (1 ng/ml) and TNF-α (10 ng/ml) stimulation or silencing (IDO-KD) using small interfering RNA (siRNA) technology.

Results
Compared with the single dose, two-dose hUCMSCs were more effective in improving LV performance, attenuating cardiac dilation, reducing cardiomyocyte apoptosis and cardiac fibrosis. Two-dose hUCMSC therapy significantly increased Treg number in the heart and peripheral blood, accompanied by increased cardiac IDO expression. Compared with the control hUCMSCs, IDO-OE hUCMSCs significantly enhanced Treg and Th2 cell responses and decreased systemic Th17 cell responses and Th1 cell numbers in the mediastinal lymph nodes. Treatment with IDO-OE hUCMSCs significantly improved LV remodeling and dysfunction. However, treatment with IDO-KD hUCMSCs had opposite effects in rats.

Conclusions
Administration of two-dose hUCMSCs has better therapeutic effects than single-dose therapy for inhibiting myocardial inflammation to improve LV function in DCM rats. These effects are associated with upregulating IDO expression and its systemic anti-inflammatory activities.
Detection of circulating tumor cells: opportunities and challenges
Authors: Ju Siwei , Chen Cong , Zhang Jiahang , Xu Lin , Zhang Xun , Li Zhaoqing , Chen Yongxia , Zhou Jichun , Ji Feiyang , Wang Linbo 
Published: August 2022

AbstractCirculating tumor cells (CTCs) are cells that shed from a primary tumor and travel through the bloodstream. Studying the functional and molecular characteristics of CTCs may provide in-depth knowledge regarding highly lethal tumor diseases. Researchers are working to design devices and develop analytical methods that can capture and detect CTCs in whole blood from cancer patients with improved sensitivity and specificity. Techniques using whole blood samples utilize physical prosperity, immunoaffinity or a combination of the above methods and positive and negative enrichment during separation. Further analysis of CTCs is helpful in cancer monitoring, efficacy evaluation and designing of targeted cancer treatment methods. Although many advances have been achieved in the detection and molecular characterization of CTCs, several challenges still exist that limit the current use of this burgeoning diagnostic approach. In this review, a brief summary of the biological characterization of CTCs is presented. We focus on the current existing CTC detection methods and the potential clinical implications and challenges of CTCs. We also put forward our own views regarding the future development direction of CTCs.