Fecal microbiota transplantation for treatment of non-alcoholic fatty liver disease:Mechanism,clinical evidence,and prospect

The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.

Present and prospect of transarterial chemoembolization combined with tyrosine kinase inhibitor and PD-1 inhibitor for unresectable hepatocellular carcinoma

In this editorial,we comment on the article(World J Gastrointest Oncol 2024;16:1236-1247),which is a retrospective study of transarterial chemoembolization(TACE)combined with multi-targeted tyrosine kinase inhibitor(TKI)and programmed cell death protein-1(PD-1)inhibitor for the treatment of unresectable hepatocellular carcinoma(HCC).Herein,we focus specifically on the mechanisms of this triple therapy,administration sequence and selection of each medication,and implications for future clinical trials.Based on the interaction mechanisms between medications,the triple therapy of TACE+TKI+PD-1 is proposed to complement the deficiency of each monotherapy,and achieve synergistic antitumor effects.Although this triple therapy has been evaluated by several retrospective trials,it is still controversial whether the triple therapy achieves better clinical benefits,due to the flawed study design and heterogeneity in medications.In addition,the administration sequence,which may greatly affect the clinical benefit,needs to be fully considered at clinical decision-making for obtaining better prognosis.We hope that this editorial could contribute to the design and optimization of future trials.

Sparse antenna array design methodologies:A review

Designing a sparse array with reduced transmit/receive modules(TRMs)is vital for some applications where the antenna system’s size,weight,allowed operating space,and cost are limited.Sparse arrays exhibit distinct architectures,roughly classified into three categories:Thinned arrays,nonuniformly spaced arrays,and clustered arrays.While numerous advanced synthesis methods have been presented for the three types of sparse arrays in recent years,a comprehensive review of the latest development in sparse array synthesis is lacking.This work aims to fill this gap by thoroughly summarizing these techniques.The study includes synthesis examples to facilitate a comparative analysis of different techniques in terms of both accuracy and efficiency.Thus,this review is intended to assist researchers and engineers in related fields,offering a clear understanding of the development and distinctions among sparse array synthesis techniques.

Update report on the quality of gliomas radiomics:An integration of bibliometric and radiomics quality score

BACKGROUND Despite the increasing number of publications on glioma radiomics,challenges persist in clinical translation.AIM To assess the development and reporting quality of radiomics in brain gliomas since 2019.METHODS A bibliometric analysis was conducted to reveal trends in brain glioma radiomics research.The Radiomics Quality Score(RQS),a metric for evaluating the quality of radiomics studies,was applied to assess the quality of adult-type diffuse glioma studies published since 2019.The total RQS score and the basic adherence rate for each item were calculated.Subgroup analysis by journal type and research objective was performed,correlating the total RQS score with journal impact factors.RESULTS The radiomics research in glioma was initiated in 2011 and has witnessed a surge since 2019.Among the 260 original studies,the median RQS score was 11,correlating with a basic compliance rate of 46.8%.Subgroup analysis revealed significant differences in domain 1 and its subitems(multiple segmentations)across journal types(P=0.039 and P=0.03,respectively).The Spearman correlation coefficients indicated that the total RQS score had a negative correlation with the Journal Citation Report category(-0.69)and a positive correlation with the five-year impact factors(0.318)of journals.CONCLUSION Glioma radiomics research quality has improved since 2019 but necessitates further advancement with higher publication standards.

生物标志物在脓毒症早期诊断及预后预测中的应用

近年来,脓毒症早期诊断和预后的生物标志物研究备受关注。当前大多数生物标志物敏感性和特异性不足,缺乏研究证据。该文就常见生物标志物及组合在脓毒症早期诊断及预后判断中的应用价值进行综述,以期为临床提供参考。

Mg-6Zn-3Sn合金的均匀化热处理及其对显微组织和力学性能的影响

利用DSC、OM、XRD、SEM、TEM、维氏硬度计和万能试验机,研究Mg-6Zn-3Sn合金均匀化过程中的显微组织和力学性能演变,分析合金过烧的原因和扩散动力学,确定合金的均匀化制度。结果表明,单级均匀化处理后,Mg_(2)Zn_(3)相分解,同时伴随着Mg_(2)Sn相的析出。当均匀化温度上升到350℃时,Mg_(2)Zn_(3)相导致合金的过烧。合金合适的均匀化制度为(335℃,24 h)+(400℃,6 h)。在双级均匀化过程中,合金的硬度持续下降,力学性能呈现先升后降的趋势,这与Zn和Sn原子的固溶和Mg_(2)Sn相的析出有关。

Tailoring the microstructural characteristic and improving the corrosion resistance of extruded dilute Mg-0.5Bi-0.5Sn alloy by microalloying with Mn

Mg-0.5Bi-0.5Sn alloys with and without microalloying with 0.5 wt%Mn were subjected to extrusion,and the effect of Mn microalloying on the microstructural characteristic and corrosion behavior of the extruded alloys was investigated.The results indicated that the average grain size and the density of dislocations decreased,and a new Mg_(26.67)Mn_(65.47)Fe_(7.86)second phase as well as grain boundary segregation of Sn atoms could be observed in certain micro-regions of the extruded dilute Mg-0.5Bi-0.5Sn-0.5 Mn alloy.The tailoring of microstructure resulted in the significant enhancement in corrosion resistance(R_(p)increased from 1095.91Ωcm^(2)to 5008.79Ωcm^(2)).In addition,grain boundary segregation resulted in intergranular corrosion and led to the dissolution of Sn atoms.Hence,the dissolution rate of the matrix in Mg-0.5Bi-0.5Sn-0.5Mn alloy could be inhibited by the corrosion product film containing an intermediate product(SnO_(2)).

Effects of traditional Chinese medicine nursing combined with conventional nursing in patients with chronic obstructive pulmonary disease:a meta-analysis

Objective: This meta-analysis aims to evaluate the effects of traditional Chinese medicine(TCM) nursing combined with conventional nursing in patients with chronic obstructive pulmonary disease(COPD).Methods: Data were collected from the databases of PubMed, Embase, the Cochrane Library, Web of Science, Google Scholar,China National Knowledge Infrastructure(CNKI), WanFang Data(WF) and VIP Database, including literature regarding the effects of TCM nursing combined with conventional nursing in patients with COPD published before January 2017. The Jadad scale was used to assess the quality of the eligible literature. The weighted mean differences and odds ratios were used to analyze St. George's Respiratory Questionnaire(SGRQ) scores, pulmonary function, hospital stay, and clinical efficacy.Results: Twenty-three randomized controlled trials comprising 3116 cases(TCM nursing combined with the conventional nursing group: 1559; conventional nursing group: 1557) met the inclusion criteria. TCM nursing combined with conventional nursing was associated with a lower SGRQ score, higher forced expiratory volume in 1 second(FEV1) value, higher FEV1/forced vital capacity(FVC) value, higher FEV1% value, higher FEV1 predicted value, shorter hospital stay, and preferable clinical efficacy.Conclusions: TCM nursing combined with conventional nursing emphasized that dialectical nursing can be performed preferably in patients with COPD.

GRADING OF RABBIT SKELETAL MUSCLE TRAUMA BY DIFFUSION TENSOR IMAGING AND TRACTOGRAPHY ON MAGNETIC RESONANCE IMAGING

Objective To distinguish the edema, injury, or rupture in the traumatic skeletal muscle fiber in vivo using diffusion tensor imaging （DTI） and tractography on magnetic resonance imaging （MRI）. Methods The skeletal muscle trauma models were made in 4 rabbits （ eight hindlimbs） by iron discus （ weight 1. 0 kg, diameter 6 cm） falling down vertically from 45 cm height to rabbits＇ thighs. Conventional sequences and two-dimensional （2D） diffusion-weighted （DW） spin-echo （SE） echo planar imaging （EPI） sequence with fat suppression （ b = 600 s/mm^2 ） were performed on 1.5T MRI scanner. The grading of edema, injury, and fiber rupture in the damaged muscle were made according to their histopathological views, which was consistent with the images. The mean apparent diffusion coefficient （ADC） values and fractional anisotropy （FA） values were measured from the region of interests （ROIs） of all groups on 2D DW images used for tractography. Analysis of variance test was performed to analyze all data. Results ADC values of the areas in normal muscle, edema muscle, injury muscle, and ruptured muscle were （6. 12±1.34 ） × 10^-3, （ 6.38±1.30 ） × 10^-3, （ 8.06±0. 97 ） × 10^-3, and （ 9. 57±0. 93 ） × 10^-3 mm^2/s, respectively. There was significant difference among groups （P 〈0. 001 ）, but no difference between edema muscle and normal muscle group （P 〉0. 05）. The FA values of normal muscle, edema muscle, injury muscle, and ruptured muscle were 0. 42±0. 12, 0. 36±0. 12, 0. 26±0. 09, 0. 12±0. 08, respectively, with a significant difference among groups （ P 〈 0. 001 ）. In the edema muscle, the tracking cross-fiber could be seen but it decreased slightly. In the injury muscle, the tracking fiber decreased markedly. In the ruptured muscle, the transverse-orientation tracking fiber vanished, yet some interrupted longitudinal-orientation tracking fiber could be found. Conclsion The edema, injury, and rupture of muscle fiber in rabbit damaged skeletal muscle can be verified according to the ADC and the FA on DTI and tractography.

The impact of work support and organizational career growth on nurse turnover intention in China

Objective:The paper aimed to explore the impact of work support and potential for career advancement on the nurse turnover intention in order to find an effective approach to curb high turnover.Methods:A cross-sectional survey of 526 nurses from eight teaching hospitals in Tianjin,China,was conducted to test the hypothesized multilevel model.The organizational career growth scale,work support scale,and the nurse turnover intention scale were used to measure the effect of organizational career growth and work support on nurse turnover intention.Finally,SPSS 17.0 and AMOS 17.0 software were used to analyse the relationship of these variables.Results:The score of the three scales nurse turnover,organizational career growth,and work support were 1.98±0.60,2.40±0.50,and 4.06±0.98,respectively.The total and direct effects of work support on turnover intention were
0.361(p<0.01)and
0.147(p<0.01),respectively.The indirect effect was
0.169 with a 95%bootstrap confidence interval of
0.257 to
0.102.Conclusion:The study showed a lack of work support negatively and directly associated with nurse turnover intention.Additional opportunities for career growth within the organization may strengthen the effect of work support and consequently increase the retention of qualified nursing staff.

MiR-21/RASA1 axis affects malignancy of colon cancer cells via RAS pathways

AIM:To determine how the oncogene mi R-21 regulates the RAS signaling pathways and affects colon cancer cell behaviors.METHODS:RAS p21 GTPase activating protein 1(RASA1) protein expression in six colon cancer cell lines was assessed by Western blot.Colon cancer RKO cells were chosen for transfection because they are KRAS wild type colon cancer cells whose RASA1 expression is significantly decreased.RKO cells were transfected with vectors overexpressing or downregulating either mi R-21 or RASA1.Furthermore,a luciferase reporter assay was used to determine whether RASA1 is a gene target of mi R-21.Then,changes in m RNA and protein levels of RASA1,RASGTP,and other components of the RAS signaling pathways were assessed in transfected RKO cells by real-time quantitative reverse transcription-polymerase chain reaction,Western blot and immunoprecipitation.Finally,cell proliferation,apoptosis,invasion,and tumorformation ability w ere assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye assay,flow cytometry,transwell assay,and animal experiment,respectively.RESULTS:RASA1 protein levels were significantly decreased in RKO cells compared with the other 5 colon cancer cell lines,and RASA1 was confirmed as a target gene of mi R-21.Interestingly,RASA1 m RNA and protein levels in pre-mi R-21-LV(up-regulation of mi R-21) cells were lower than those in anti-mi R-21-LV(down-regulation of mi R-21) cells(P < 0.05).In addition,pre-mi R-21-LV or si RASA1(down-regulation of RASA1) cells showed higher cell proliferation,reduced apoptosis,increased expression of RAS-GTP,p-AKT,Raf-1,KRAS,and p-ERK1/2,and higher invasion and tumor formation ability,compared with control,antimi R-21-LV or pc DNA3.1-RASA1(up-regulation of RASA1) cells(P < 0.05).CONCLUSION:RASA1 is a target gene of mi R-21,which promotes malignant behaviors of RKO cells through regulation of RASA1 expression.

The relationships among perceived organizational support,intention to remain,career success and self-esteem in Chinese male nurses

Aim:The purpose of this study was to investigate the relationships among perceived organizational support,intention to remain,career success and self-esteem in male nurses in China.Background:Recently,turnover is considered increasingly more normal.Male nurses could be stabilized by improving their perceived organizational support,career success and selfesteem.Design:A cross-sectional design was used in the present study.Method:405 full-time male Registered Nurses,from Grade A hospitals in Tianjin,were surveyed.Pearson correlation,Cronbach's alpha coefficient and structural equation modelling were conducted in the study.Results:The results illustrated that self-esteem mediated the relationship between perceived organizational support and career success.Career success mediated the relationship between self-esteem and intention to remain.Conclusion:Hospitals should pay more attention to the benefits of positive personality trait on working motivation.It is meaningful to enhance perceived organizational support,career success and self-esteem in the working process so that nurses are willing to stay in the current employment.

Decreased expression of DAB2IP in pancreatic cancer with wild-type KRAS

BACKGROUND: KRAS mutation plays an important role in the pathogenesis of pancreatic cancer. However, the role of wild-type KRAS in the progression of pancreatic cancer remains unknown. The present study was to investigate the expression of the Ras GTPase activating protein (DAB2IP) in pancreatic cancer and its clinical significance. METHODS: The expression of DAB2IP in pancreatic cancer cell lines and normal human pancreatic ductal epithelial cells was analyzed by Western blotting and realtime quantitative reverse transcription-PCR (qRT-PCR). The KRAS mutational types of pancreatic cancer tissues obtained from pancreatic cancer patients (n=20) were also analyzed. Subsequently, DAB2IP expression was detected in pancreatic cancer tissues, adjacent and normal pancreatic tissues (n=2) by immunohistochemistry, and the relationship between DAB2IP expression and the clinical characteristics of patients was evaluated. RESULTS: Western blotting and qRT-PCR results showed that DAB2IP expression in pancreatic cancer cells with wild-type KRAS was lower than that in those with mutation-type KRAS and normal human pancreatic ductal epithelial cells (P【0.05). Immunohistochemistry showed that DAB2IP expression was lower in pancreatic cancer tissues than that in adjacent and normal pancreatic tissues (Z=-4.000, P=0.000). DAB2IP expression was lower in pancreatic cancer patients with the wild-type KRAS gene than that in those with KRAS mutations (WilcoxonW=35.000, P=0.042). Furthermore,DAB2IP expression in patients with perineurial invasion was lower than that in those without invasion (WilcoxonW=71.500, P=0.028). DAB2IP expression was lower in patients with more advanced stage than that in those with early clinical stage (WilcoxonW=54.000, P=0.002). CONCLUSIONS: DAB2IP expression was reduced in patients with pancreatic cancer compared with those with no cancer. DAB2IP expression was correlated with the KRAS gene, perineurial invasion and clinical stage of the disease. Our data indicated that DAP2IP expression can be used as a potential prognostic indicator and a promising molecular target for therapeutic intervention in patients with pancreatic cancer.

眼眶孤立性纤维瘤12例临床影像学分析

目的:探讨眼眶孤立性纤维瘤(SFT)的彩色多普勒超声及磁共振成像(MRI)特点。方法:回顾性病例研究。收集2013-04/2018-08天津医科大学眼科医院收治的12例眼眶SFT患者的临床资料,均行彩色多普勒超声和MRI平扫、增强及动态增强检查,分析其临床影像学特点。结果:纳入的12例患者中男7例,女5例,病程3mo^20a(平均3.2±5.2a),6例为首次发病,6例为复发病例;均为单眼发病,其中左眶8例,右眶4例。肿瘤位于眼球后肌锥间隙内5例,肌锥间隙外3例,跨肌锥间隙内、外4例;肿瘤形状呈卵形9例,不规则形3例,边界均清晰。超声表现为低回声10例,不均匀回声2例;12例彩色多普勒血流显像(CDFI)均可见血流信号,阻力指数(RI)平均值0.70,PW均测得动脉频谱。MRI表现在T1WI均呈等信号;T2WI呈低信号5例,等信号3例,中高信号4例,内部信号均匀9例,不均匀3例;增强后12例均呈显著强化,10例均匀强化,2例不均匀强化。动态增强扫描的时间-信号强度曲线(TIC)7例为速升平台型,5例为速升速降型。结论:眼眶SFT在彩超显示低回声、富血供的实体瘤,MRI提示T1WI呈等信号,T2WI信号混杂,增强后显著强化,动态增强TIC曲线以速升型为主的特征性表现对诊断具有重要意义。

Effectiveness of mindfulness-based stress reduction and mindfulness-based cognitive therapies on people living with HIV:A systematic review and meta-analysis

Objective:To assess the effects of mindfulness-based therapies(MBTs)on the outcomes of people living with HIV.Methods:During 2014,we searched the PubMed/MEDLINE,Embase,Web of Science,Cochrane Library,and CBM databases to identify randomized and non-randomized controlled studies which compared participants receiving mindfulness-based therapies(MBTs),including mindfulness-based stress reduction(MBSR)and mindfulness-based cognitive therapy(MBCT),with participants in control groups.The psychological,biochemical,clinical,and behavioral outcomes of the study participants were analyzed.Two separate reviewers independently performed the study selection,data extraction,and quality assessment tasks,and a meta-analysis of selected studies was performed using RevMan software.Results:Seven articles describing results obtained with a total of 620 HIV-infected individuals enrolled in six randomized trials and one quasi-experimental trial were included in the final meta-analysis.The overall methodological quality of the studies was moderate,as most study criteria were unclear and subject to a high risk of bias.Patients receiving MBT experienced significantly decreased feelings of stress after 8 weeks(p=0.03)of MBT,and decreased feelings of depression after both 8 weeks(p=0.04)and 6 months(p=0.02).Additionally,some patients receiving MBSR training or MBCT showed improved CD4^(+)counts at 8 weeks and 6 months,respectively.Conclusion:While MBT produced psychological benefits in HIV infected patients,any improvements in CD4^(+)counts were not robust.Additional studies with longer term follow-up periods and larger sample sizes are required to ascertain the effectiveness of such interventions.

Job burnout and turnover intention among nurses in China:the mediating effects of positive emotion

Objective: The aim of this study was to explore whether positive emotion mediates the relationship between job burnout and turnover intentions among Chinese nurses.Methods: A cross-sectional survey was conducted in the present study. Full-time registered nurses(n = 150) from Grade A hospitals in Tianjin were surveyed. Pearson correlation, hierarchical regression analyses, and the Sobel test were used in the study.Results: The results illustrated that positive emotion mediated the relationship between burnout and nurses' turnover intention.Conclusions: Nursing administrators should pay more attention to the benefits of positive emotions on working motivation.It is helpful to relieve burnout in the working process so that nurses are willing to remain in their current employment.

Prevalence of frailty among nursing home residents in China:a systematic review and meta-analysis

Background:The prevalence of frailty among nursing home residents is high.However,in China,prevalence of frailty keeps unknown in this population.The purpose of this meta-analysis is to assess the prevalence of frailty and prefrailty and find out the factors related to the prevalence of frailty among nursing home residents in China.Methods:We searched both English(PubMed,Cochrane Library,Embase,Web of Science and Scopus)and Chinese(CNKI,WanFang,SinoMed,and VIP)databases from their inception date until 15 September 2020.Two reviewers independently screened literature,extracted data,and evaluated the risk of bias included studies.Stata12.0 software was used to conduct meta-analysis.Results:A total of 16 studies were included in this review,involving 7,777 nursing home residents.The prevalence of frailty ranged from 29.2% to 66.6% in the included studies.The pooled prevalence of frailty and prefrailty were 49%(95%CI:43-55%)and 42%(95%CI:34–50%),respectively.The assessment tool(P<0.001),gender(P<0.001),self-rated health(P<0.001)and type of institution(P<0.001)were significantly associated with the prevalence of frailty among nursing home residents in China.Conclusions:The prevalence of frailty among nursing home residents in China was relatively high.Considering the adverse health outcomes of frailty,nursing home administrators should screen frailty regularly,identify the risk factors of frailty,take actions accordingly and improve the frailty status for older adults.

Relationships among achievement motivation,meta-learning capacity and creativity tendencies among Chinese baccalaureate nursing students

capacity and creativity tendencies among Chinese baccalaureate nursing students.Design:Cross-sectional study design.Methods:A convenient sample of 445 baccalaureate nursing students were surveyed in two universities in Tianjin,China.Students completed a questionnaire that included their demographic information,Achievement Motivation Scale,Meta-Learning Capacity Questionnaire,and Creativity Tendencies Scale.Pearson correlation was performed to test the correlation among achievement motivation,meta-learning capacity and creativity tendencies.Hierarchical linear regression analyses were performed to explore the mediating role of meta-learning capacity.Results:The participants had moderate levels of achievement motivation(mean score 2.383±0.240)and meta-learning capacity(mean score 1.505±0.241)and a medium-high level of creativity tendency(mean score 1.841±0.288).Creativity tendencies was significantly associated with both achievement motivation and meta-learning capacity(both P<0.01).Furthermore,meta-learning capacity mediated the relationship between achievement motivation and high creativity tendencies.Conclusion:The study hypotheses were supported.Higher achievement motivation,and meta-learning capacity can increase creativity tendencies of baccalaureate nursing students,and meta-learning capacity was found to mediate the relationship between achievement motivation and creativity tendencies.Nursing educators should pay attention to the positive role of meta-learning capacity in nursing students’learning,and make them more confident when they finish their studies.

Impact of self-directed learning readiness and learning attitude on problem-solving ability among Chinese undergraduate nursing students

Objective: To explore the effects of self-directed learning readiness and learning attitude on problem-solving ability among Chinese undergraduate nursing students. Methods: A convenience sampling of 460 undergraduate nursing students was surveyed in Tianjin, China. Students who participated in the study completed a questionnaire that included social demographic questionnaire, Self-directed Learning Readiness Scale, Attitude to Learning Scale, and Social Problem-Solving Inventory. Pearson’s correlation analysis was performed to test the correlations among problem-solving ability, self-directed learning readiness, and learning attitude. Hierarchical linear regression analyses were performed to explore the mediating role of learning attitude. Results: The results showed that learning attitude (r=0.338, P<0.01) and self-directed learning readiness (r=0.493, P<0.01) were positively correlated with problem-solving ability. Learning attitude played a partial intermediary role between self-directed learning readiness and problem-solving ability (F=74.227, P<0.01). Conclusions: It is concluded that nursing educators should pay attention on students’ individual differences and take proper actions to inspire students’ self-directed learning readiness and learning attitude.

The effect of empowerment education on depression level and laboratory indicators of patients treated with hemodialysis:a meta-analysis

Objective:The objective of this study was to evaluate the effect of empowerment education on depression level and laboratory indicators of patients treated with hemodialysis.Methods:We searched databases including Cochrane Library,Web of Science,Embase,PubMed,Chinese Biomedical Literature Database(CBM),Chinese Academic Journals Full-text Database(CNKI),VIP,and Wanfang.We included all the researches about the application of empowerment education in patients treated with hemodialysis.We used RevMan 5.3 to analyze the data after assessing the quality of researches.Results:We included 10 studies eventually.The results of meta-analysis showed that the self-efficacy[MD=1.10,95%confidence interval(CI;0.71,1.48),P<0.01],depression[MD=-6.94,95%CI(-8.53,-5.34),P<0.01],serum creatinine[Scr;MD=-116.46,95%CI(-171.90,-61.03),P<0.01],albumin[Alb;MD=2.93,95%CI(2.00,3.86),P<0.01],and blood urea nitrogen[BUN;MD=-0.95,95%CI(-1.89,-0.01),P=0.05]in the empowerment education group had significantly statistical difference compared with those in the usual education group.However,there was no significant difference in hemoglobin[Hb;MD=3.03,95%CI(-0.64,6.70),P=0.11]between two groups.Conclusions:Empowerment education can improve the self-efficacy in patients treated with hemodialysis,relieve depression,and improve Scr,Alb,and BUN.However,there is no significant improvement in Hb;it needs further exploration in clinical practice.