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You are done with your research work and have gathered good scientific data that require international submission and recognition. It is understood, that for every science researcher, more than money it has been always considered that the biggest reward is ones publication and will be referred as Your name et al . In this regard you are planning to get a peer reviewed publication in an international journal however you are confused with the correct style of writing an international standard manuscript. Hence, considering the enormous struggles faced by Indian students, I decided to short list some pertinent points that are essential to follow which would make it easier to write: a. Selection of Journal- A very integral part of your article publication is to select the appropriate journal. Some major pints to consider are- i. Look for journal which matches your work and data requirements ii. Always look for peer reviewed journals iii. Be clear with the publication charges aswell b. Journal requirements- Once you have selected the journal name, you should thoroughly note down their requirements. c. Preparing illustrations- Research articles become more meaningful and acceptable through presence of relevant illustatrions hence, it is advisable to always include them. International journals accept only image and eps files. The eps files are those images files which are generated with adobe illustrator software. Download this software free trial or purchase it and practice with it. d. Creating your draft- Writing a scientific manuscript is a big challenge as you need to have good writing skills and should have good scientific justifications. Ideally, the main contents of the manuscript should be – i. Abstract- Every manuscript require a suitable abstract which describe and present your work and data in brief. It should have a good hypothesis with good justifications. Again this could be divided into brief sections of an introduction, methodology applied for your work, results obtained and the conclusion. ii. Introduction- Begin with a brief biological description of the topic and state what you intend to do. You should elaborately mention the hypothesis with clear justifications to perform the study. One line sentence on what is your strategy and how are you going about it. Next, you provide brief mention on the national and international status of your work with appropriate references whether or not the same strategy was implemented earlier in your lab or elsewhere. Never miss out this information, it should be clearly indicated in your manuscript. If it’s a novel study, then mention its importance and anything related which has been done before. iii. Materials and methods- This section is extremely crucial as you need to provide the techniques here. Read a lot of research articles especially this section before writing this part. It is advisable to write in parts and in fresh minds. It must be well drafted with accurate values and measurements. Any change or modifications would be directly questioned by your reviewer. Describe the technology or equipment briefly and you must clearly explain the source of the study and the control. In this context, you give details about the treatment done on the model of study, like mouse, cell types or humans. Describe the software type you used in details and all the data analysis using statistical tools mentioning the version number. iv. Results and Discussion- This section describes your data and all the findings of your study addressing to all your questions for the study. Ideally, you need to include the statistical calculations and data analysis reports pertaining to either relative or absolute comparisons. If any negative finding is there it should also be justified appropriately. Most often you could combine the results with discussion together in one section. Here you could explain the data in details with proper justifications and reference. v. Conclusions- Finally, this section you mention about the values of your study to the scientific community and its potential uses in the near future for further studies. You could also provide the inferences to the welfare of the mankind and hence, to your nation. e. Plagiarism- A common cause of manuscript REJECTION is plagiarism- any work which is unlawfully copied in this present manuscript, including sentences or your images from previously published research articles or any source is illegal and punishable once found guilty. While writing be extremely vigilant you keep your work, your language and your words ‘ORIGINAL’. Never do anything which will spoil all your efforts done for the past several years. f. Bibliography tool- Drafting a good manuscript requires a lot of literature survey and hence, correct inclusion of the reference for all the information provided is essential. Almost every statement you provide here has to be referred by a publication with mention of the year. Hence in this regard, you should use an ideal software tool like the Endnote which is very useful. Just register and download it, you may use it for free at first as trial version. Using this tool requires a little experience and most often it is advisable to work online. g. Manuscript editing- The language of the manuscript should be simple English that could be easily understood by readers from all parts of world including China, Japan, Germany and others. Ideally, you should use single format of Times New Roman and 12 font size. Always write with accuracy and fresh mind. Never use superlative words like ‘extremely’, ‘first time’, ‘best’, ‘worst’. Also strictly avoid writing provocative or contradictory statements against any previous work. This will create a negative feedback on your work in the scientific community. h. Working with your coauthors- Remember this work is not only the work of the first author, there are efforts put in by other members of your team. Hence, you should give importance to them aswell. To make your work easier, you could divide the draft version to your coauthors who had given significant time in the study. Keep revising your writeup and the draft versions should be regularly exchanged amongst your coauthors especially those who participated in the study. At the end of this article, remember there is a section where you are supposed to explain the work done by your peers/coauthors. i. Selection of peer reviewers- It is always advisable to choose reviewers who are your team’s peers or people who are aware of your team and acknowledges your work. j. Work with your mentor- Once your draft is completed, you send your mentor to give his edits and there will be several rounds of polishing which could be a little frustrating and time taking. Never give up, you should feel excited that your work will be getting published and the biggest reward is that your work will be always remembered once you are no longer there. “Do you need assistance in your manuscript writing – write to us”

1. Introduction According to International Diabetes Federation (IDF) the prevalence of Diabetes has increased by 4 fold, since the 1980s, 578 million in 2019 and 642 million people projected worldwide by the year 2040 (1). Type 2 Diabetes mellitus (T2DM) is increasing at an alarmingly high rate in east Asian population, China being highest with 116.4 million and second highest 77 million in India (1). Its understood that there is a sudden trend in massive urbanization and upgradation in the East Asian countries. The outcome of which is attributed to significant change in lifestyle which has a direct impact on diabetes mellitus (2) . As compared to the Caucaceans, according to Lim et al, 2017, the major factors that contribute to the outgrowth of T2DM in this subcontinent includes, juvenile T2DM, a reduced body mass index, increased visceral adiposity and ultimately the malfunctioning of pancreatic beta cells (2). Hence, considering such a crisis it is pertinent to control the disease with drugs which could potentially control the blood glucose levels simultaneously controlling the associated complications. In this regard, a group of Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors have been regarded of remarkable significance. The different drug names include canagliflozin, dapaglifozin, empagliflozin, etc (3). The major functioning of these inhibitors is to control the glucose reabsorption in kidney which has a direct positive impact on the stabilization of blood pressure alongwith weight control and hence the blood sugar levels (4). In this article, we are going to review the role of this group of drugs in diabetes management on the East Asian population. 1. Diabetes mellitus in East Asian population-an overview 2.1 Prevalance and Epidemiology in East Asia- According to the International Diabetes Federation (IDF), https://www.diabetesatlas.org , the prevalence rate of diabetes mellitus globally is 9.3% for 2019 while it may dramatically increase by 10.2% by the year 2030 (5) . It has been reported that due to sedentary lifestyle, lowered body mass index, juvenile diabetes and economic outgrowth, the East Asian countries including China (1), (6), India, Japan, Korea and Pakistan have an increasing trend of the disease (7). In Korea, over a period of 40 years, an estimated 9.9% increase in its incidence has been reported (1) (8). Interestingly, in the south east Asia itself, the IDF has mentioned that there were more than a million deaths in 2019 itself. 2.2 Factors responsible for the increased rates in East Asians As compared to the rest of the world, the East Asians are suffering more due to several clinical phenotypes. In this context, scientists have elaborately classified the various factors attributed to this population (9), (2),(5). Such factors have been discussed in this section- 2.2.1 Poor body mass index (BMI)- In China, the biggest risk factor attributed to central obesity (5). A Bone Mass Index of ≥28 kg/m2 and ≥50 years in female populations are the second highest risk factors compared to males. In Japan and Korea, the risk factors were also found out to be ageing and targeting male populations. Visceral adiposity is considered a major contributor and indicator (10). Visceral fats release a large amounts of adipokines and cytokineswhich targets organs and hence complications. 2.2.2 Insufficient beta-cell response - To counter insulin resistance , insufficient Beta cells of Pancreas in Asian population have been understood to be a major factor (11). Ohn et al., 2016, has shown through genomic studies in Korean population that reduced beta cell functioning affects insulin sensitivity and hence thereby the glucose tolerance (12). According to the Joint Asia Diabetes Evaluation (JADE) cohort study, almost every 1 in 5 adult Diabetic had a history of young age Diabetes (13). 2.2.3 Urbanization - In China the development of Diabetes is a big threat hence, considered as an uncontrolled epidemic. The vital factors which include advanced economic growth, demographic transitions, urbanizations, change in food habits and lifestyles (2). Interestingly, a recent report by Pradeepa in 2017, stated that a speedy socioeconomic transition with an increase in urbanization and industrialization are the main reasons for the high incidence rate in India (14). 2.2.4 Vascular complications - An early onset of T2DM in the younger generation of the East Asians have potentially affected the micro and macro vascular constitutions in the form of increased inflammatory markers, chronic inflammation cardiovascular manifestations and acute renal injury (15). 2.2.4 Vascular complications - An early onset of T2DM in the younger generation of the East Asians have potentially affected the micro and macro vascular constitutions in the form of increased inflammatory markers, chronic inflammation cardiovascular manifestations and acute renal injury (15). 3. Therapy with the SGLT2 inhibitors Regardless of the availability of a considerable number of antiglycemic medications, the control of blood glucose with complications have not yet been successful (16). However, recent advances on SGLT2 inhibitors have been widely accepted as they are considered to act in an insulin independent manner with no involvement in insulin secretion or action (16). Dapagliflozin, empagliflozin, tofogliflozin, the generic names of such drugs been orally given to reduce blood glucose levels in T2DM patients (17). 3.1Pharmacology and mode of action- Canagliflozin competitively inhibits SGLT1 and SGLT2 proteins, with high potency and selectivity for SGLT2. Inhibition constant ( K i) values for SGLT1 and SGLT2 were 770.5 and 4.0 nM, respectively (18). 3.2 Drug efficacy and safety The safety and efficacy of SGLT2 inhibitors has been explained pictorially in Figure 2 . Due to the safe use of SGLT2 inhibitors on Diabetic patients in Asia, JADE has recommended SGLT2 inhibitor be a preferred add on therapy for T2DM patients suffering from Cardiovascular or chronic kidney complications (19). 3.2.1 Glycemic control - Its reported that the risk of hypoglycemia is lower with SGLT2 inhibitors, as compared to sulfonylureas (20, 21) . 5 mg and 10 mg of Dapagliflozin have been found to reduce HbA1c significantly as a monotherapy (22) and a dual therapy with metformin (23, 24). Despite of its association with genito- urinatory SGLT2 inhibitor based therapy is considered ideal anti-hypoglycemic (24). Table 1 - The Glycemic efficacy of SGLT2 inhibitors in East Asian population ( 31264765) Study Design and population Intervention Glycemic effects Inagaki N, et al. 2014 Phase III, 24-week double-blind randomized study; Japanese T2DM (N=272) Canagliflozin (100, 200 mg); placebo −0.74% (100 mg); −0.76% (200 mg); +0.29% (placebo) Ji L, et al. 2014 Phase III, 24-week double-blind randomized study; drug-naïve Asian T2DM (N=393) Dapagliflozin (5 or 10 mg); placebo −1.04% (5 mg); −1.11% (10 mg); −0.29% (placebo) Kaku K, et al. 2014 Phase III, 24-week double-blind randomized study; Japanese T2DM (N=261) Dapagliflozin (5 or 10 mg); placebo −0.41% (5 mg); −0.45% (10 mg); −0.06% (placebo) 3.2.2 Cardiovascular outcomes- Hayashi et al., 2017 have reported an increase in High Density Lipoproteins and suppression of the atherogenic marker soluble Low Density Lipoprotein on 80 Japanese T2DM patients under Dapagliflozin administration (25, 26). As per our knowledge, till date there has been almost no report on the direct consequence of SGLT2 inhibitors on the Asian patients. Over the past decade, several clinical trials have been undergoing as listed in Table 2. Once they are being approved then the regionwise analysis would begin. 3.2.3 Diabetic Kidney manifestations - As compared to the rest of the world, there has been critical thinking on the function of SGLT2 inhibitors in Asian T2DM patients suffering from Kidney ailments. Treatment with SGLT2 inhibitor, ipragliflozin on Japanese patients in an Long‐Term ASP1941 Safety Evaluation in Patients with Type 2 Diabetes with Renal Impairment (LANTERN) study, described the potential use of the drug’s safety and efficacy on moderately impaired renal patients (27). Such results support the potential use of SGLT2-inhibitors in addition to RAAS inhibitors on Diabetic patient suffering from kidney ailment. Hence, such positive data on East Asians, are crucial to perform long term studies in validating the renoprotective effects of these drugs (19). 3. 3 Clinical trial studies with SGLT2 inhibitors - The details of the clinical Trial on Cardiovascular manifestations with SGLT2 inhibitors have been provided in Table 2 and the associated renal outcomes have been provided in Table 3. Table 2 - The cardiovascular outcome trial of the SGLT2 inhibitor-based studies as adapted from Deerochanawong et al, 2019 (28). Abbtns: MACE - Major Adverse Cardiac Events, HR- Hazard Ratio TRIAL NAME ESTIMATED DATE OF COMPLETION REPORTS MultiCentric and evaluating the effect of Dapagliflozin on Cardiovascular Events(DECLARE TIMI58) (Dapagliflozin vs placebo), N = 17 160 April 2019 3 point MACE-pvalue 0.17 CV Death –HR 0.83 CV Death- pvalue 0.005 CANagliflozin cardioVascular Assessment Study (CANVAS) (canagliflozin vs placebo), N = 10 142 Feb 2017 3 point MACE-pvalue 0.02 CV Death-HR 0.87 CV Death-Pvalue (0.18) EMPA‐REG OUTCOME (empagliflozin vs placebo), N = 7020 - 3 pont MACE-pvalue 0.04 CVDeath –HR 0.62 CV Death-Pvalue <0.001 Ertugliflozin Treatment in T2D with Vascular Disease (VERTIS CV Study) June 2020 Ongoing Table 3 - The clinical outcomes of SGLT2 inhibitors on Diabetic Renal functions (29) and (30) TRIAL NAME ESTIMATED YEAR OF COMPLETION REPORTED OUTCOMES Canagliflozin on Renal and Cardiovascular Outcomes in Participants with Diabetic Nephropathy (CREDENCE) April 2019 The result outcomes are highly satisfactory, best over 20 yrs period time. Renal and CV outcome-HR 0.7 End stage Kidney disease; Doubling of Serum Creatinine or renal death –HR 0.66 (30) EMPA (empagliflozin)‐KIDNEY SEPT 2017 Renal and CV outcome-p value 0.18 Albumin Creatinin Ratio pvalue 0.51 (31) Canagliflozin on Renal Endpoints in Adult Participants with T2D (CANVAS-R) FEB 2017 - 4. Concluding remarks The SGLT2 inhibitors are considered well tolerated due to their safe functions, have already been treated as next line of treatment after Metformin in T2DM patients. They are effective as monotherapy or in combination with other drugs. Researchers have suggested that they should be administered to patients with a number of complications including cardiorenal manifestations. These are found to considerably normalize the BMI and weight gains in East Asian patients. Although clinical trials are providing very positive results about the safety and efficacy of these drugs thay still have adverse effects which need to be monitored appropriately. 1. 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IDEALLY, IT IS WELL UNDERSTOOD SINCE ANCIENT DAYS THAT EVERY STUDENT’S FRIEND SHOULD BE A BOOK AN ESSENTIAL ENTITY WITHOUT WHICH NO ONE CAN GROW AND DEVELOP IN THE FUTURE AND SHOULD BE TREATED AS AN ASSET OF EVERY HOUSEHOLD. MAJORITY OF BOOKS ARE IDEALLY NON COMMERCIAL AND HENCE THE ONLY WAY TO IMPART EDUCATION IS THROUGH BOOKS. INTRIGUINGLY, BOOKS CAN NEVER BE REPLACED BY ANYTHING ELSE, FOR EVERY FIELD THERE IS A BIBLE AND MUST BE A NECESSITY. FOR REFERENCES, NOTES PREPARATION, BASIC CONCEPT FOUNDATION, CORRECT INFORMATION AND FOR THE FUTURE GENERATION WE NEED BOOKS AND SHOULD BE ALWAYS RESPECTED.