The development and validation of the Satisfaction Questionnaire for Osteoporosis Prevention in Malaysia

Purpose: To develop and validate the English version of the Satisfaction Questionnaire for Osteoporosis Prevention (SQOP) in Malaysia.Methods: The SQOP was modified from the Osteoporosis Patient Satisfaction Questionnaire and developed based on literature review and patient interviews. Face and content validity were established via an expert panel. The SQOP consists of two sections: clinical services and types of counseling. There were 23 items in total, each with a five-point Likert-type response. Satisfaction score was calculated by converting the total score to a percentage. A higher score indicates higher satisfaction. English speaking, non-osteoporotic, postmenopausal women aged ≥50 years were included in the study. Participants were randomized to either the control or intervention group. Intervention participants were provided counseling, whereas control participants received none. Participants answered the SQOP at baseline and 2 weeks later.Results: A total of 140 participants were recruited (control group: n=70; intervention group: n=70). No significant differences were found in any demographic aspects. Exploratory factor analysis extracted seven domains. Cronbach’s a for the domains ranged from 0.531–0.812. All 23 items were highly correlated using Spearman’s correlation coefficient 0.469–0.996 (

Practical guide in using insulin degludec/insulin aspart: A multidisciplinary approach in Malaysia

Insulin degludec/insulin aspart (IDegAsp) co-formulation provides both basal and mealtime glycaemic control in a single injection. The glucose level-lowering efficacy of IDegAsp is reported to be superior or non-inferior to that of the currently available insulin therapies with a lower rate of overall hypoglycaemia and nocturnal hypoglycaemia. An expert panel from Malaysia aims to provide insights into the utilisation of IDegAsp across a broad range of patients with type 2 diabetes mellitus (i.e. treatment-naïve or insulin-naïve patients or patients receiving treatment intensification from basal-only regimens, premixed insulin and basal–bolus insulin therapy). IDegAsp can be initiated as once-daily dosing for the main meal with the largest carbohydrate content with weekly dose adjustments based on patient response. A lower starting dose is recommended for patients with cardiac or renal comorbidities. Dose intensification with IDegAsp may warrant splitting into twice-daily dosing. IDegAsp twice-daily dosing does not need to be split at a 50:50 ratio but should be adjusted to match the carbohydrate content of meals. The treatment of patients choosing to fast during Ramadan should be switched to IDegAsp early before Ramadan, as a longer duration of titration leads to better glycated haemoglobin level reductions. The pre-Ramadan breakfast/lunch insulin dose can be reduced by 30%–50% and taken during sahur, while the pre-Ramadan dinner dose can be taken without any change during iftar. Education on the main meal concept is important, as carbohydrates are present in almost all meals. Patients should not have a misconception of consuming more carbohydrates while taking IDegAsp

Modifiable Risk Factor Score and Fecundability in a Preconception Cohort in Singapore

Importance: Although multiple modifiable risk factors have been identified for reduced fecundability (defined as lower probability of conception within a menstrual cycle), no scoring system has been established to systematically evaluate fecundability among females who are attempting to conceive. Objective: To examine the association of a risk score based on 6 modifiable factors with fecundability, and to estimate the percentage reduction in incidence of nonconception if all study participants achieved a minimal risk score level. Design, Setting, and Participants: This population-based cohort study obtained data from the S-PRESTO (Singapore Preconception Study of Long-Term Maternal and Child Outcomes) prospective cohort study. Females of reproductive age who were trying to conceive were enrolled from February 2015 to October 2017 and followed for 1 year, ending in November 2018. Data were analyzed from March to May 2022. Exposures: A reduced fecundability risk score was derived by giving participants 1 point for each of the following factors: unhealthy body mass index, unhealthy diet, smoking, alcohol intake, folic acid supplement nonuser, and older maternal age. Total scores ranged from 0 to 6 and were classified into 5 levels: level 1 (score of 0 or 1), level 2 (score of 2), level 3 (score of 3), level 4 (score of 4), and level 5 (score of 5 or 6). Main Outcomes and Measures: Fecundability, measured by time to conception in cycles, was analyzed using discrete-time proportional hazards models with confounder adjustment. Results: A total of 937 females (mean [SD] age, 30.8 [3.8] years) were included, among whom 401 (42.8%) spontaneously conceived within 1 year of attempting conception; the median (IQR) number of cycles before conception was 4 (2-7). Compared with participants with a level 1 risk score, those with level 2, 3, 4, and 5 risk scores had reductions in fecundability of 31% (adjusted fecundability ratio [FR], 0.69; 95% CI, 0.54-0.88), 41% (FR, 0.59; 95% CI, 0.45-0.78), 54% (FR, 0.46; 95% CI, 0.31-0.69) and 77% (FR, 0.23; 95% CI, 0.07-0.73), respectively. Assessment of the population attributable fraction showed that all participants achieving a minimal (level 1) risk level would be associated with a reduction of 34% (95% CI, 30%-39%) in nonconception within a year. Conclusions and Relevance: Results of this study revealed the co-occurrence of multiple modifiable risk factors for lowered fecundability and a substantially higher conception rate among participants with no or minimal risk factors. The risk assessment scoring system proposed is a simple and potentially useful public health tool for mitigating risks and guiding those who are trying to conceive.publishedVersionPeer reviewe

Metronomic chemotherapy prevents therapy-induced stromal activation and induction of tumor-initiating cells

Although traditional chemotherapy kills a fraction of tumor cells, it also activates the stroma and can promote the growth and survival of residual cancer cells to foster tumor recurrence and metastasis. Accordingly, overcoming the host response induced by chemotherapy could substantially improve therapeutic outcome and patient survival. In this study, resistance to treatment and metastasis has been attributed to expansion of stem-like tumor-initiating cells (TICs). Molecular analysis of the tumor stroma in neoadjuvant chemotherapy–treated human desmoplastic cancers and orthotopic tumor xenografts revealed that traditional maximum-tolerated dose chemotherapy, regardless of the agents used, induces persistent STAT-1 and NF-κB activity in carcinoma-associated fibroblasts. This induction results in the expression and secretion of ELR motif–positive (ELR(+)) chemokines, which signal through CXCR-2 on carcinoma cells to trigger their phenotypic conversion into TICs and promote their invasive behaviors, leading to paradoxical tumor aggression after therapy. In contrast, the same overall dose administered as a low-dose metronomic chemotherapy regimen largely prevented therapy-induced stromal ELR(+) chemokine paracrine signaling, thus enhancing treatment response and extending survival of mice carrying desmoplastic cancers. These experiments illustrate the importance of stroma in cancer therapy and how its impact on treatment resistance could be tempered by altering the dosing schedule of systemic chemotherapy

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Transcriptomal Changes Associated With Doxorubicin- or Paclitaxel-induced Stromal Senescence and Treatment Responses in Breast Cancer

腫瘤基質的微環境 (microenvironment) 會顯著影響腫瘤形成和進展。癌相關纖維細胞 (cancer associated fibroblasts; CAFs) 是腫瘤基質的一種主要細胞類型，他們籍由多重影響參與鄰近癌細胞的腫瘤病理。最近的研究顯示，這些細胞會因暴露在低於致死的游離輻射或化學治療藥物後，被誘發進行類似於細胞老化 (cell senescence) 的變化。許多在體外或老鼠異種移植模型(xenograft)顯示，此壓力激發過早衰老 (stress-induced premature senescence; SIPS) 表現型的基質細胞，籍由旁分泌 (paracrine) 作用和細胞外基質重塑 (extra cellular matrix remodeling)，可以促進腫瘤生長和侵襲 (invasion)。支持腫瘤基質與惡性進展間關係的臨床證據，來自於腫瘤基質基因表現型態 (gene expression profiles) 與癌症病患治療的相關性。由於基質和衰老的纖維細胞 (senescence fibroblast) 對於腫瘤的調節關係，在這裡我們想問，臨床的化學治療方式是否可能導致乳腺癌相關纖維細胞 (CAFs) 過早衰老，以及參與這一過程的基因表達圖譜是否與乳癌的治療結果有關聯。在這研究中，我們發現把新鮮分離的乳腺CAFs暴露在臨床相關劑量的doxorubicin或paclitaxel後，會有類似衰老的表現型與明顯的時間依賴性基因表現變化。用功能聚類分析發現這些基因大部分是參與細胞間的連繫，旁分泌作用和基質重塑。有趣的是，我們發現在兩個系列的乳癌術前輔助化療試驗的基因體資料庫中，這基因表達圖譜能有效地分辨出患者是否完全緩解 (pathologic complete remission; pCR) (odds ratio 4.5-8.8, P < 0.0001)。基於這些發現，我們可以合理推論，化療誘發的腫瘤基質變化在治療反應占有重要的角色，而相關的分子圖譜 (molecular profile) 在臨床上可能可以作為乳癌治療時的生物標誌 (biomarker)。The stromal microenvironments have been found to have profound influence on the development and progression of malignant tumors. Cancer-associated fibroblasts (CAFs) are a fundamental cell type in the tumor stroma found to actively partake in tumor pathology through their pleiotropic influences on neighboring cancer cells. Current evidence suggests that when stromal cells are exposed to sub-lethal injuries such as ionizing radiation and/or cytotoxic agents, they may develop a senescent-like growth arrest program. The results of numerous studies, either in vitro or mouse xenograft models, indicate that stromal cells displaying this stress-induced premature senescence (SIPS) phenotype secrete paracrine-signaling and matrix remodeling factors that could promote growth and invasiveness of tumors cells. The role of stroma in malignant tumor malignant is supported by significant associations of the gene expression profiles derived from the tumor stroma or CAFs and the survival or treatment outcome of cancer patients. Given the tumor-modulating activities of the stroma and the senescent fibroblasts, it is not clear whether clinical chemotherapy (CT) regimens could induce premature senescence in breast CAFs and whether the expression profiles of the genes involved in this process could influence the treatment outcome of breast cancer. In this study, we found that after treating a specimen of freshly isolated breast CAFs with doxorubicin or paclitaxel at clinical relevant dosing, these stromal cells will undergo senescence-like phenotype coupled with distinct and time-dependent transcriptomal alterations. Based on functional clustering analyses on these profiles, it seems that majority of the genes code for factors that participate in cell-to-cell communications, paracrine signaling and matrix remodeling. The findings from two series of breast cancer neoadjuvant CT trials indicated this gene expression profiles effectively distinguishes the patients with pathologic complete remission (pCR) from those who are not (odds ratio 4.5-8.8, P < 0.0001). Based on these findings, it seems reasonable that the CT-altered tumor stroma played an important role in treatment response and the associated gene expression profile may be applicable in clinical practice as biomarker for breast cancer therapy.表次...................................................iii 圖次....................................................iv 附圖次..................................................vi 縮寫表..................................................vii 壹、緒論.................................................1 貳、文獻探討.............................................3 一、 乳癌概況.......................................3 二、 乳癌的治療與預後的評估.........................3 三、 腫瘤基質細胞.................................. 4 四、 癌相關纖維細胞 (Cancer-associated fibroblasts ; CAFs)..........................................5 五、 腫瘤微環境 (Tumor microenvironment)............7 參、材料與方法...........................................10 一、試劑和抗體.......................................10 二、儀器設備.........................................11 三、組織標本，細胞培養，乳腺CAF純化..................11 四、化療藥物處理乳腺CAFs.............................12 五、PKH2標定.........................................12 六、SA-beta-galactosidase (SA-β-gal)染色............12 七、流式細胞儀 (Flow Cytometry, FACS)................12 八、免疫螢光染色 (Immunofluorescent staining)........13 九、西方點墨法.......................................13 十、RNA萃取與純化....................................14 十一、 即時定量聚合酶連鎖反應........................14 十二、 微陣列分析....................................15 十三、 數據統計分析..................................15 肆、結果.................................................16 一、在體外，乳癌相關纖維細胞 (Cancer-associated fibroblasts) 對於therapeutically relevant cytotoxic stimuli的反應..........................16 二、術前輔助化療後乳癌基質中乳腺CAFs表現型的變化.....17 三、TRCS引起基因轉錄體 (Transcriptomal) 的變化與遠處基 質生態之關係.....................................18 四、乳腺CAFs對TRCS延遲性反應之基因表達圖譜與乳癌對術前 輔助化療反應的關連性.............................19 五、在術前化療後，臨床乳癌樣本之乳腺CAFs基因的變化...20 伍、討論.................................................21 陸、總結及未來方向.......................................23 柒、參考文獻.............................................24 表次 表1.用於SA-β-gal和免疫螢光染色的腫瘤樣本的臨床特徵......33 表2.參與細胞間的連繫功能的基因...........................34 表3.TRCS後不同的時間點，乳腺CAFs的DEGs與pCR的勝算比......45 圖次 圖1.基質對TRCS反應的實驗示意圖...........................46 圖2.經TRCS處理的乳腺CAFs和對照組，其SA-β-gal的活性及細胞 核的表現型...........................................47 圖3.經TRCS處理的乳腺CAFs和對照組，其有絲分裂蛋白 (Mitotic protein) 的變化......................................48 圖4.TRCS處理的乳腺CAFs時間依賴性的表現型化...............49 圖5.臨床乳癌患者的腫瘤組織切片...........................50 圖6.乳癌患者在接受術前輔助化療後，SA-β-gal活性的百分比..51 圖7.維恩圖顯示乳腺CAFs經化療後的差異表達基因.............52 圖8.TRCS誘發乳腺CAFs基因轉錄體變化與時間的關係...........53 圖9.經doxorubicin-或paclitaxel-induced TRCS的乳腺CAFs，三 個時間間隔的DEGs.....................................54 圖10.經TRCS處理後，乳腺CAFs豐富功能基因類別 (EFGCs) 與時間 依賴性的變化........................................55 圖11.經TRCS處理之乳腺CAFs，與細胞間連繫有關的EGFCs變化...56 圖12.不同的時間間隔，DEGs與治療反應的關聯性..............57 圖13.晚期DEGs 對預測病理完全緩解 (pCR) 的勝算比 (odds ratio)..............................................58 圖14.在術前化療後，臨床乳癌樣本之乳腺腫瘤基質基因IFIT3和 COL5A1 RNA的變化....................................59 圖15.在術前化療後，臨床乳癌樣本之α-SMA, IFIT3和COL5A1的免 疫螢光染色及百分比..................................60 附圖次 附圖1.新鮮分離的乳腺CAFs免疫螢光染色.....................61 附圖2. 經TRCS-treated的乳腺CAFs, DNA含量與時間依賴性的變 化.................................................6

Random walk down ses

Several studies have reported empirical evidence that stock returns are contrary to the random walk hypothesis. Although capital market efficiency has been a popular area for research in financial economics, most of the documented work has been on developed markets like the NYSE. Relatively little work has been carried out on our local stock market. This project is not a redress in any way, but only sets out to investigate the general behavior of our market and investors.ACCOUNTANC

A Soft Technique for Fault Detection and Identification in Mechanical Systems

There are two approaches to diagnose a fault for mechanical systems: add hardware sensors, design software algorithms. This paper will focus on software approach to detect and identify a class of faults. The proposed approach uses an estimator built to enable the detection of fault occurrences through comparison of observed states with available sensor information, while other nonlinear estimator is used to identify the fault extracting its signature. Advantages of the proposed fault detection and identification methods are that they are based on the established dynamic model, they do not require acceleration measurements. Experimental study is given to illustrate the effects of the proposed approach

Applied predictive control

The presence of considerable time delays in the dynamics of many industrial processes, leading to difficult problems in the associated closed-loop control systems, is a well-recognized phenomenon. The performance achievable in conventional feedback control systems can be significantly degraded if an industrial process has a relatively large time delay compared with the dominant time constant. Under these circumstances, advanced predictive control is necessary to improve the performance of the control system significantly. The book is a focused treatment of the subject matter, including the fundamentals and some state-of-the-art developments in the field of predictive control. Three main schemes for advanced predictive control are addressed in this book: • Smith Predictive Control; • Generalised Predictive Control; • a form of predictive control based on Finite Spectrum Assignment. A substantial part of the book addresses application issues in predictive control, providing several interesting case studies for more application-oriented readers. Thus, while the book is written to serve as an advanced control reference on predictive control for researchers, postgraduates and senior undergraduates, it should be equally useful to those industrial practitioners who are keen to explore the use of advanced predictive control in real problems. The prerequisite for gaining maximum benefit from this book is a basic knowledge of control systems, such as that imparted by a first undergraduate course on control systems engineering. Advances in Industrial Control aims to report and encourage the transfer of technology in control engineering. The rapid development of control technology has an impact on all areas of the control discipline. The series offers an opportunity for researchers to present an extended exposition of new work in all aspects of industrial control