bluuebunny/crossref_metadata_2025_split huggingface dataset:
m6A regulator-based methylation modification patterns and characterization of tumor microenvironment in acute myeloid leukemia
Authors: Xu Zi-jun , Wen Xiang-mei , Zhang Yuan-cui , Jin Ye , Ma Ji-chun , Gu Yu , Chen Xin-yi , Xia Pei-hui , Qian Wei , Lin Jiang , Qian Jun 
Published: May 2022

Abstract
RNA N6-methyladenosine (m6A) is the most common and intensively studied RNA modification that critically regulates RNA metabolism, cell signaling, cell survival, and differentiation. However, the overall role of multiple m6A regulators in the tumor microenvironment (TME) has not yet been fully elucidated in acute myeloid leukemia (AML). In our study, we explored the genetic and transcriptional alterations of 23 m6A regulators in AML patients. Three distinct molecular subtypes were identified and associated with prognosis, patient clinicopathological features, as well as TME characteristics. The TME characterization revealed that m6A patterns were highly connected with metabolic pathways such as biosynthesis of unsaturated fatty acids, cysteine and methionine metabolism, and citrate cycle TCA cycle. Then, based on the differentially expressed genes (DEGs) related to m6A molecular subtypes, our study categorized the entire cohort into three m6A gene clusters. Furthermore, we constructed the m6A score for quantification of the m6A modification pattern of individual AML patients. It was found that the tumor-infiltrating lymphocyte cells (TILs) closely correlated with the three m6A clusters, three m6A gene clusters, and m6Ascore. And many signaling pathways were involved, including glycogen degradation, drug metabolism by cytochrome P450, pyruvate metabolism, and so on. Our comprehensive analysis of m6A regulators in AML demonstrated their potential roles in the clinicopathological features, prognosis, tumor microenvironment, and particularly metabolic pathways. These findings may improve our understanding of m6A regulators in AML and offers new perspectives on the assessment of prognosis and the development of anticancer strategy.
Blocking the Expression of the Nitrate Reductase Gene OsNia3 Confers Early Maturation in Rice
Authors: Han RuiCai , Wang YuPeng , Li ChenYan , Wu ZiMing , Huang RenLiang 
Published: May 2022

Abstract
Early flowering is a major contributing factor to early crop maturation and is a prerequisite for the expansion of crop production to high latitudes with short growing seasons as well as for annual double/triple cropping systems. Nitrogen is the mineral element most limiting to plant growth and, consequently, also to crop yield. Nitrogen also plays a role in the regulation of flowering time. Here, we show that OsNia3 is a member of the rice nitrate reductase (NR) gene family. OsNia3 was found to be expressed in stem nodes of rice, while the loss of its function led to a reduction in plant height mainly due to disrupted nitrate metabolism at the site of OsNia3 expression. The expression levels of genes related to nitrate transport, nitrate assimilation, and ammonium assimilation, such as OsNia1, OsNRT2.3A, and OsNGS1, increased in the leaves of osnia3 mutant plants, concomitant with an increase in the activity of the nitrogen metabolism pathway. The ammonium and amino acid contents in the leaves also increased in the osnia3 mutant, as did the chlorophyll content. Phenotypic analysis showed that the osnia3 mutant exhibited a shorter growth period compared with wild-type plants; nevertheless, yield was not significantly affected in mutant plants. The deletion of the OsNia3 gene led to the upregulation of genes related to the photoperiod regulation network (OsGI, OsHd1, and OsHd3a), which likely promoted early flowering. These results indicated that OsNia3 is involved in the floral inhibition pathway (OsGI-OsHd1-OsHd3a) in rice under long-day conditions. Our findings provide a theoretical and material basis for the coordination and improvement of early maturity and high-yield traits in rice breeding.
Development and validation of a multiple factor-based prognostic score system of thrombosis in polycythemia vera (MFPS-PV)
Authors: Gu Wenjing , Zhang Yuhui , Sun Ting , Mankai Ju , Xiaofan Liu , Xue Feng , Chen Yunfei , Wei Liu , Zhang Donglei , Huiyuan Li , Wang Wentian , Chi Ying , Yang Renchi , Bai Jie , Fu Rongfeng , Zhang Lei 
Published: May 2022

Abstract
Thrombosis is an important cause of death in patients with polycythemia vera (PV). This study aimed to develop and validate a multiple factor-based prediction model of thrombosis and to propose risk-adapted treatment strategies for the 2016 World Health Organization-defined PV. The study involved 301 patients in the training cohort and another 194 patients in the external validation cohort. Multivariate analysis indicated that age ≥ 57 years (hazard ratio [HR] 2.586, p = 0.006), cardiovascular risk factors (HR 4.599, p = 0.005), previous thrombosis (HR 4.780, p < 0.001), and at least one high-risk mutation for thrombosis (mutations in DNMT3A, ASXL1, and BCOR/BCORL1) (HR 3.732, p < 0.001) were independent risk factors for thrombosis. After assigning HR-weighted scores to each risk factor, a multiple factor-based prognostic score system of thrombosis (MFPS-PV) was developed, classifying patients into low-risk (0–1 points), intermediate-risk (2–3 points), and high-risk (≥ 4 points) groups. Patients in the three groups had significantly different thrombosis-free survival rates (p < 0.001). The MFPS-PV outperformed the conventional two-tiered stratification (C-index 0.746 vs 0.643) and remained consistent during external validation. Finally, a risk-adapted therapeutic strategy was established based on the MFPS-PV. In conclusion, the MFPS-PV, integrating genetic and clinical characteristics for the first time, can significantly predict thrombosis and has great therapeutic implications.
Influence of physical activity on the progression of osteoarthritis of the nonoperative hip after unilateral total hip arthroplasty: A prospective cohort study
Authors: Sekita Junya , Takahira Naonobu , Watanabe Hiroyuki , kudo Sho , Kusaba Atsushi , Kondo Saiji 
Published: May 2022

Abstract
Background
Total hip arthroplasty (THA) is one of the most effective treatments for hip pain and hip dysfunction. There are, however, problems associated with postoperative changes in the nonoperative hip joint and in particular, it is not uncommon for patients with osteoarthritis (OA) to experience increased pain and progression of OA. Appropriate physical activity (PA) and exercise can help maintain and improve physical function in OA patients, but excessive activity may increase the risk of progression of OA. This study aimed to clarify the influence of PA on the progression of OA of the nonoperative hip after unilateral THA.
Design:
This prospective cohort study was conducted from six to 24 months post-THA. Subjects were female patients with hip OA who had undergone unilateral THA. The primary outcome was change in minimal joint space (MJS) (ΔMJS, MJS at 24 months - MJS at six months). Daily step count and moderate to vigorous physical activity (MVPA) were also measured. Patients were divided into two groups by Kellgren-Lawrence (KL) grade (0 or ≥ 1). To identify factors that influence ΔMJS, a generalized linear model approach was used, with adjustment factors (age, body weight, and MJS at six months), KL grade, PA (daily step count/MVPA), and interaction terms between PA and KL grade as explanatory variables.
Results
Eighty-five patients were analyzed. ΔMJS was 0.18 mm at 24 months post-THA. The interaction term between daily step count and KL grade significantly influenced the progression of OA. The regression coefficient of daily step count for ΔMJS was significant in the KL ≥ 1 group, but not in the KL = 0 group. A model with adjustment factors, an interaction term, and both PA measures showed that daily step count and decreasing MVPA increased ΔMJS.
Conclusions
PA influenced the progression of OA in patients with KL grade ≥ 1, but did not influence onset in patients without OA post-THA. Excessive daily step count and/or low MVPA may be a risk factor for the progression of OA.
Acceptability to donate human breast milk among post-natal mothers at St Francis hospital Nsambya Uganda: A mixed method study
Authors: Ahmed Mohammed A.M. , Namisi Charles Patrick , Kirabira Nakibuuka Viktoria , Lwetabe Micheal Webba , Rujumba Joseph 
Published: May 2022

Abstract
Background
Whereas the World Health Organisationrecommends use of donated Human Breast Milk (HBM) as the second best option for preterm babies, whose mothers lack breast milk, HBM donation is not a practice in Uganda. We assessed the level of and factors associated with acceptance to donate HBM among postnatal mothers at St. Francis Hospital Nsambya (SFHN).
Methods
A cross-sectional sequential explanatory mixed method study was used. A questionnaire on socio-demography, awareness and likely acceptability to donate HBM was administered to 410 postnatal mothers at SFHN. Data was entered in Epi Info 7 and analysed using STATA version 13 for multivariate logistic regression to predict factors for acceptance to donate HBM. Focus Group Discussions (4) and Key Informants Interviews (4) were used to explore factors influencing behaviours to donate HBM. Qualitative data was analysed using content thematic approach.
Results
Overall the acceptance to donate HBM was 77.6% and the significant factors were; willingness to express HBM (aOR 7.5,95%CI: 3.01 -18.); wet-nursing knowledge (aOR 2.3,95%CI: 1.1–5.0) and under-5 years clinic visit (aOR 21.3, 95% CI: 2.3–196.9). Emerging themes for accepting to donate HBM were; wet-nursing experience, confidence to donate HBM and its perceived effectiveness. There were concerns about safety and adequacy of HBM, fear to transmit criminality and mental illness through HBM.
Conclusion
Acceptance to donate HBM among postnatal mothers at St. Francis Hospital Nsambya was very high. Willingness to express and store breast milk, prior knowledge about wet nursing and visit to an under five OPD were associated with acceptance. Thus establishing a HBM bank is feasible.
Assessing Clinical Trial Failure Risk Factors And Reasons In Gastric Cancer
Authors: zhang zikai Billy , Yin Junyi , Su Yang , Jiang Hong 
Published: May 2022

Abstract
Gastric cancer is one of the leading cancer-related death causes. Enormous efforts have been focused on this field in these years. However, clinical trial failure is becoming a massive obstacle for researchers to apply their research results for clinical use. This study aimed to analyse the reasons behind clinical failures and identify potential risk factors of clinical trial failures. On December,1,2021, we queried ClinicalTrials.gov for gastric cancer listed in phase II/III. A total of 567 trials are included. 10.2% of these trials are failed. 19 (3.4%) were terminated for good reasons, and 39 (6.9%) were terminated for bad reasons. For trials that terminated due to good reasons, 13 (68.4%) trials were terminated for efficacy reasons. 3 (15.8%) trials were terminated for safety reasons. For trials that terminated due to bad reasons, 18 (46.2%) trials were terminated due to recruitment failure. Multicentre (P-value = 0.026) and countries (P-value = 0.055) are potential risk factors for clinical failures in the simple logistic regression model. In multiple logistic model, we find the odds ratio of the anticipated accrual number is 0.993 (P-value = 0.029) and the anticipated accrual number combined multicentre is 0.999 (P-value = 0.045).The major reasons for gastric cancer trial terminations are recruitment failure, efficacy, and safety reasons. We identified potential risk factors associated with trial failure. By better understanding these reasons, we can prevent potential clinical failures in the future.
Community pharmacists’ counseling practices and patient experiences about topical corticosteroids – an online survey in the Klang Valley, Malaysia
Authors: Nathan Abigail Dayang , Shankar Pathiyil Ravi , Sreerramare Chandrashekhar T 
Published: May 2022

Abstract
Background
Community Pharmacists (CPs) play an important role in patient counselling regarding the use of topical corticosteroids. We assessed the CP’s self-reported counselling practices regarding topical corticosteroids and patients’ reported counselling experiences.
Methods
A previously developed questionnaire was adapted to the Malaysian context. A random sample of 364 registered CPs practicing in three states Selangor, Kuala Lumpur, and Putrajaya were invited for an online survey. CPS questionnaire covered CPS’s perceived patient knowledge about topical corticosteroid (TCS) use, CPs counseling practices, and their perceived barriers to counselling. Thirty patients were also selected from five pharmacies i.e., six consecutive patients who consulted each CP were invited to participate in the patient survey by completing a checklist about their experiences regarding the counselling received.
Results
A majority (> 90%) of the CPs most of the time explained to the patients that medication was TCS and frequency and duration of application but only 10% correctly identified scenarios needing medical referrals. Only about half of the CPs always explained about side effects, strength, efficacy, and storage of TCS. The two main barriers were patients’ negative perception of TCS (65.4%) and pharmacists’ lack of time for counselling (49.7%). Counselling practice score was associated with CPs age (aOR 0.86, 95%CI 0.78–0.94), pharmacists’ recommendation on TCS use (aOR 0.11, 95%CI 0.02–0.61), and time spent on counselling (aOR 1.42, 95%CI 1.13–1.64).
Conclusion
CPs counselling practices to their patient about the use of TCS requires improvement. Continuing education and hands-on training are needed for CPs regarding counselling about TCS use.
Rapid intraoperative immunohistochemistry (RD-IHC) is a useful tool in intraoperative pathologic diagnosis
Authors: Zhang Yu , Cheng Xian-kui , Yao Zhi-gang , Qin Ye-jun 
Published: May 2022

Abstract
Intraoperative pathologic diagnosis for lesions plays an important role in determining the surgery procedure. Accurate pathological diagnosis could lead to earlier, more effective treatments. But the accuracy of frozen sections pathology diagnosis in controversial cases maybe discount. Most of the time, the surgeon had to wait for the post-operative immunohistochemistry results to decide whether to have a second operation. In our study, rapid intraoperative immunohistochemistry was used for the diagnosis of controversial cases, which greatly improved the diagnostic accuracy and reduced rates of deferred diagnoses. Also, the total procedures of rapid intraoperative immunohistochemistry can be finished within 10 min that allows its general application for intraoperative frozen section diagnosis. In conclusion, rapid intraoperative immunohistochemistry could be a useful tool in intraoperative pathologic diagnosis.
Correlation between TACS and FAP with Prognosis of Clear Cell Renal Cell Carcinoma Patient
Authors: Warli Syah Mirsya , Putrantyo Ivan , Laksmi Lidya Imelda 
Published: May 2022

Abstract
Background: Despite recent promising findings from immunotherapy and other targeted medicines, individuals with metastatic Clear Cell Renal Cell Carcinoma (mCCRCC) still have a poor prognosis. Biomarkers associated with metastatic status in CCRCC are important for early detection and for the identification of new therapeutic targets. Fibroblast activation protein (FAP) expression is associated with development of early metastases and worse cancer-specific survival. Tumor-associated collagen signature (TACS) is type of collagen that develop during tumor growth and associated with tumor invasion.Methods: 26 metastatic clear cell renal cell carcinoma patients that underwent nephrectomy were admitted to this study. Data regarding age, sex, Fuhrman’s grade, tumor diameter, staging, FAP expression, and TACS grading were collected. Spearman rho test was used to correlate FAP expression and TACS grading in both primary tumors and metastases, and with patients age and sex.Results: FAP expression correlated positively with TACS degree (Spearman rho test r = 0.51; p = 0.0001). FAP was positive in 25 (96%) of all intratumor samples and positive in 22(84%) of all stromal sample.Conclusion: FAP can be used as prognostic factor in metastatic CCRCC, its presence can predict aggressiveness of mCRCC and poorer outcome in patient. Furthermore TACS can be also used for prediction of aggressiveness and metastasis due to the changes are necessary for tumor to invade other organs.
Study on fermentation mechanisms of Arisaema cum Bile based on microbial diversity-odor characteristic components
Authors: Wu Xu , Wang Jing , Zou Ting , He Su-Rong , Wu Ya-Nan , Wen Si-Hua , Li Ya-Juan , Liu Qian , Chen Xi , Qi Chun-Yan , Zhang Qiao , Song Yi-Jun , Zhao Chong-Bo , Wang Chang-Li 
Published: May 2022

Abstract
Arisaema cum Bile (Dan Nan Xing, DNX) had a history of nearly one thousand years in clinical application of traditional Chinese medicine. It was mainly used to treat pediatric diseases such as convulsion and hyperthermia. However, the current fermentation technology of DNX was lack of scientific explanation, and there was no unified standard. Therefore, this paper study on the relationship between microorganisms and odor by 16SrRNA and GC-IMS technology in the fermentation technology of DNX, and expounds the scientificity of DNX "fermenting in bovine gallbladder for 100 days" and "increasing bile fermentation DNX ". This study prepared DNX with different fermentation time and different fermentation times of numbers, according to the records of 《Xiao Er Yao Zheng Zhi Jue》(小儿药证直决) and 《Yi Sheng Wei Lun》(颐生微论). 16SrRNA sequencing showed that Firmicutes, Proteobacteria, streptophyta, Bacteroidetes and actinobacteria were active in DNX samples. GC-IMS technology detected 41 volatile substances in DNX, mainly including alcohols, esters, aldehydes etc. According to the results of KEGG analysis between flora and odor metabolism pathway, the above flora may affect the content of esters, alcools, acids and aldehyde compounds of DNX by alanine, aspartate and glutamate metabolism, propanoate metabolism, pyruvate metabolism ways, etc. Spearman correlation analysis showed that Nocardiopsis and Acidovorax were significantly negatively correlated with ammonia. Ammonia was one of the main volatile components of the stink smell of DNX, and the stink smell of DNX was weakened, which was convenient for clinical patients to take. There was no significant difference in the relative abundance of Acidovorax between FJ3M and FJ33M, but the abundance was lower in FJ6M. Nocardiopsis began to increase in FJ3M DNX sample, and the abundance was higher in FJ6M. In addition, compared with MJ, it was found that both Acidovorax in nature and in bovine bile played a role in DNX fermentation, but Acidovorax in bovine bile contributed more. Nocardiopsis was carried by bovine bile itself. This result was helpful to expound the scientificity of "DNX fermentation for 100 days" in the《Xiao Er Yao Zheng Zhi Jue》, and can provide a scientific basis for the fermentation and processing technology of DNX.
Impact of obstructive ventilatory impairment on intraoperative bleeding during laparoscopic hepatectomy
Authors: Nakamura Masanori , Okamura Yukiyasu , Sugiura Teiichi , Ashida Ryo , Ohgi Katsuhisa , Yamada Mihoko , Otsuka Shimpei , Nakayama Goro , Kodera Yasuhiro , Uesaka Katsuhiko 
Published: May 2022

Abstract
Purpose: An animal model of laparoscopic hepatectomy showed that bleeding from the hepatic vein is influenced by airway pressure. However, there are little research reports on how airway pressure leads to risks in clinical practice. The main objective of this study was to investigate the impact of preoperative forced expiratory volume % in 1 second (FEV1.0%) on intraoperative blood loss in laparoscopic hepatectomy.Methods:All patients who underwent pure laparoscopic or open hepatectomy from April 2011 to July 2020 were classified into two groups by preoperative spirometry: those with obstructive ventilatory impairment (Obstructive group; FEV1.0%< 70%) and those with normal respiratory function (Normal group; FEV1.0%≥ 70%). Massive blood loss was defined as 400 mL for laparoscopic hepatectomy.Results:In total, 247 and 445 patients underwent pure laparoscopic and open hepatectomy, respectively. Regarding laparoscopic hepatectomy group, blood loss was significantly greater in the Obstructive group (122 vs. 100 mL, P = 0.042). Multivariate analysis revealed that high IWATE criteria scores (≥ 7, odds ratio [OR]: 4.50, P = 0.004) and low preoperative FEV1.0% (< 70%, OR: 2.28, P = 0.043) were independent risk factors for blood loss during laparoscopic hepatectomy. In contrast, FEV1.0% did not affect the blood loss (522 vs. 605 mL, P = 0.113) during open hepatectomy. Conclusion: Obstructive ventilatory impairment (low FEV1.0%) may affect the amount of bleeding during laparoscopic hepatectomy.
Electroacupuncture protects against cerebral ischemia-reperfusion injury via regulating P2X7R expression
Authors: Lin Feihong , Zhu Ye , Liu Haipeng , Li Shan , Huang Xuliang , Mo Yunchang , Wang Junlu , Dai Qinxue 
Published: May 2022

Abstract
Clinically, ischemic stroke is a serious disease hard to cure, therefore it is of great importance to slow down the depletion of ATP to enhance the tolerance of ischemic tissue through aggressive preconditioning. Electroacupuncture (EA) preconditioning has been reported to produce a tolerance for cerebral ischemia, with the underlying mechanism remaining unclear. Given that the P2X7 receptor (P2X7R) mediates the stimulation of microglial cells and is involved in the developmental process of cerebrum ischemia-reperfusion (I/R) damage, we hypothesized that the protective effect of Electroacupuncture preconditioning might be associated with the downregulated P2X7R. In this study, 2 '(3')-O-(4-benzoyl) adenosine triphosphate (BzATP) was utilized as a P2X7R agonist in rats with cerebral ischemia-reperfusion injury (MCAO), from which we found that EA preconditioning ameliorated neurologic scoring, decreased infarction volume, and necrotic neurons, and decreased the release of cytokines, while BzATP exacerbated cerebrum I/R damage and inflammation events compared with the favorable efficacy of EA. In addition, BzATP reversed the positive effects mediated by EA, which was consistent with increased expression of P2X7R. These findings suggest that EA induces cerebral ischemic tolerance to ischemia-reperfusion(I/R) damage by suppressing the expression of P2X7R and the release of inflammatory factors.