Our investigation identifies that knocking down mRNA for XXXX results in augmentation of pro-apoptotic pathways in two human melanoma lines.Specifically upregulated were the proteins YYYY, ZZZZ, and VVVV (see Figure 3A), to sufficient degrees that cellular apoptosis was enhanced by 80% as assessed by ***** and &&&& (see Figure 3B). XXXX serves a similar role in other settings. Smith et al previously reported in a mouse model that, compared to controls, epithelial cells from XXXX knockouts undergo more rapid apoptosis when challenged with GGGG (ref 22). Apoptosis of human eosinophils also have been shown to be enhanced when the XXXX gene is knocked down (ref 23), to a degree reflective of the corticosteroid-induced upregulation of VVVV that also triggers rapid apoptosis in an eosinophil cell line(ref 24). The relationship between XXXX and glucocorticoid receptor pathways is currently unknown. Our findings are the first to extend the potential role of the XXXX downstream pathways to human cancer cells, and raise the potential for targeted interventions in human melanoma.
We also demonstrate that the XXXX pathway in two melanoma lines is downregulated by intracellular acidification resulting from exposure to HHHH. HHHH is a pharmacotherapeutic used for decades for the treatment of malaria (ref 25), that is reasonably safe and generally well tolerated other than infrequent ocular side effects (ref 26). In our in vitro study, HHHH used in doses equivalent to standard human dosing effectively reduced intracellular pH in melanoma cells, decreased the message for XXXX, and upregulated YYYY and ZZZZ protein expression (but not VVVV) (see Figure 4A-4C). Although our study does not fully clarify the mechanisms of pH modulation of XXXX transcription, the final effect on augmentation of apoptosis was similar in degree to our XXXX knockdown model. The ability of HHHH to affect cancer cell apoptosis is a novel finding that, after additional data are obtained, may become a candidate for clinical trials of therapeutics for malignant melanoma.
* * *约翰•亨特博士,小儿胸腔科、过敏症专家和免疫学家,曾任美国弗吉尼亚大学终身副教授。发表过大量论文并被多次引用。最近出版了作品YOUR CHILD’S ASTHMA—A Guide for Parents。他非常热衷于为ACCDON提供编辑和咨询服务。
此短文由LetPub美国总公司的科学编辑撰写,英文原文如下:
Manuscript creation for English language journals. Part 1 of 2.
The following is Part 2 of a two part series on original research manuscript development. The previous blog post presented in 18 points some general principles and advice and thoughts regarding the Methods and Results sections. This current post provides advice and thoughts regarding the important Introduction and the fun opportunities available to you while writing your Discussion.
19.After crafting the Methods section and the Results section, write the Introduction. The Introduction should state the hypothesis, present what prompted you to consider this hypothesis, delineate why it is important to examine this hypothesis, provide necessary background to understand the science to be presented, and provide a very superficial overview of how you have examined the hypothesis. In the introduction you can reference your prior work, and the work of others, as they relate to your reason for undertaking the research and as background to understand the science. Brevity is important. Keep it short. As you are writing this introduction, think about how the Methods and Results support your intent.
20.Next, write the Discussion. The Discussion is the opportunity for the scientist to tell the story he or she wants to tell. Do not waste the discussion reiterating what you said in the Introduction, or restating the data that you just presented in the Results section. It is appropriate in the Discussion to state what the data presented in the results mean, why they are important, and what they imply. A Discussion section that does little more than reiterate the Introduction or Results is boring. Paragraphs that do nothing but reiterate the Results section should be deleted. The Discussion is where you tell the reader the main things that you learned from this experimental program, how this new knowledge advances the field, and what you are going to do with the knowledge.
21.Remember your list of 2-5 most important messages? Here is the most important advice for the Discussion section: organize your list of messages in order of importance (or some other logical sequence), and then use each message as the first sentence of a paragraph, sequentially, in the Discussion. Each paragraph should discuss implications of results, explain what your experimental data mean, and refer to prior publications that relate to that first sentence/message. If a point is not addressing the message in the first sentence of the paragraph, then the point shouldn’t be in that paragraph. Delete it or place it somewhere else. It is necessary and appropriate to state how your data (reported in the Results) support the main message of the paragraph. Thus your data are referred to only in the context of the paragraph’s main message.
22.Two example Discussion paragraphs are presented at the end of this post.
23.The Discussion is not a place to list a litany of articles you have read. Use only references that provide important and logical information that relates to your major messages. Craft a sensible, logical story, and craft it using as few words as possible. Remember, the Discussion is where you present and discuss the important messages you want people to learn from your investigations.
24.Your speculations about your data and the field in general can and should be incorporated into your discussion. You have an opportunity to present your conclusions and speculations here. This is the authors’ opportunity to be forward thinking, take risks, and make suggestions. A well written Discussion drives the conversation forward, proposes new explanations, identifies new hypotheses, conveys a vision, and expands the minds of all the readers.
25.In the Discussion, humbly add the limitations of the study. Every study has limitations. The most important limitation is that clinical and bench studies rarely can be applied to the individual patient with any confidence. Data are data, but a patient is not ever represented by a mean and standard deviation. An individual can be way out at the end of the bell curve and we should never pretend otherwise.
26.In your Conclusion, be careful to not generalize beyond what your data actually support. Conclusions are simple, brief, unequivocal and not speculative. Here is an example of a weak Conclusion: “Our study data suggest the possibility that XXX may someday serve as a useful clinical tool.” That previous sentence is a speculation, not a concluding fact.
27.In your Conclusion, be humble. If an intervention showed no value in your study, that doesn’t mean the intervention won’t work if used in a different population or in a different matter, or at a different time. The same is true for diagnostic testing. Likewise, if you have shown that an intervention has a beneficial mean effect in your sample population, this does not mean it will necessarily be effective in an individual patient. Evidence based medicine can be dangerously misleading in many ways. Make sure to not add to the rapidly accumulating mass of misleading evidence. Specifically, do not to try to apply group mean data to individuals.
28.With the sections of the paper all written, now go back and start cutting. Shorten your manuscript by cutting out every unnecessary concept. Language editors can cut out unnecessary words and phrases, but they have a more difficult time performing the necessary deletion of unnecessary content. The process of shortening a manuscript is designed to help the author think ever more logically, so as to convey the messages efficiently yet thoroughly.
29.Craft your abstract. There is no room for any redundancy within the abstract. Every word needs to have purpose. The conclusion in abstract should not reiterate the results. The most important and impactful data should be incorporated using numbers. Most readers will never read further than the abstract, so make sure your most important messages are stated clearly in the abstract.
30.Craft the Title honestly in a manner designed to attract attention of potentially interested readers.
Writing a manuscript is an art form as well as a scientific endeavor. An excellent manuscript conveys the authors’ important messages in as simple a manner to read as possible. Thought and time—invested in study design first, and then organizing the manuscript and identifying the messages you want to convey—are the first author’s essential first steps. A manuscript that results from following these processes is likely to be strong, and an enjoyable read.
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The following are two consecutive example paragraphs in an entirely imaginary Discussion section for a bench research project with clinical implications. Red is a single message from the list of important messages pre-selected by the authors. A single IMPORTANT message should serve as the first sentence of each paragraph. Blue is the supporting material that relates entirely and clearly to the important message in the first sentence of the paragraph. Green is the authors’ opportunity to dream and speculate about the important message of the paragraph.
Our investigation identifies that knocking down mRNA for XXXX results in augmentation of pro-apoptotic pathways in two human melanoma lines.Specifically upregulated were the proteins YYYY, ZZZZ, and VVVV (see Figure 3A), to sufficient degrees that cellular apoptosis was enhanced by 80% as assessed by ***** and &&&& (see Figure 3B). XXXX serves a similar role in other settings. Smith et al previously reported in a mouse model that, compared to controls, epithelial cells from XXXX knockouts undergo more rapid apoptosis when challenged with GGGG (ref 22). Apoptosis of human eosinophils also have been shown to be enhanced when the XXXX gene is knocked down (ref 23), to a degree reflective of the corticosteroid-induced upregulation of VVVV that also triggers rapid apoptosis in an eosinophil cell line(ref 24). The relationship between XXXX and glucocorticoid receptor pathways is currently unknown. Our findings are the first to extend the potential role of the XXXX downstream pathways to human cancer cells, and raise the potential for targeted interventions in human melanoma.
We also demonstrate that the XXXX pathway in two melanoma lines is downregulated by intracellular acidification resulting from exposure to HHHH. HHHH is a pharmacotherapeutic used for decades for the treatment of malaria (ref 25), that is reasonably safe and generally well tolerated other than infrequent ocular side effects (ref 26). In our in vitro study, HHHH used in doses equivalent to standard human dosing effectively reduced intracellular pH in melanoma cells, decreased the message for XXXX, and upregulated YYYY and ZZZZ protein expression (but not VVVV) (see Figure 4A-4C). Although our study does not fully clarify the mechanisms of pH modulation of XXXX transcription, the final effect on augmentation of apoptosis was similar in degree to our XXXX knockdown model. The ability of HHHH to affect cancer cell apoptosis is a novel finding that, after additional data are obtained, may become a candidate for clinical trials of therapeutics for malignant melanoma.
And then the next paragraph begins with the next important message in the first author’s ordered list of the important messages they want to convey in the manuscript. This simple format will help avoid rambling and hard-to-follow manuscripts, and will help the reader understand all the important work you have done.
Good luck in your manuscript writing. ACCDON is here to help!
***John Hunt, MD is a pediatric pulmonologist, allergist & immunologist and former tenured Associate Professor at the University of Virginia in the USA. He has an extensive publication history with a very high number of citations. He is the author of the recently published YOUR CHILD’S ASTHMA—A Guide for Parents. He greatly enjoys providing editorial and advisory services to ACCDON.