Swati Pal, Author at SciWriteGlobal

Aug, 2020

Small interfering RNA (siRNA) Technology

In the past two decades, there has been increasing awareness of the role RNAs play in the regulation of gene expression. The field of RNA was revolutionized with the discovery of RNA interference (RNAi).

RNAi is a regulatory mechanism seen in most of the eukaryotic cells that contain double-stranded RNA (dsRNA) which in turn triggers direct homology dependent control of gene activity. Popularly known as small interference RNAs (siRNA), dsRNA is usually 21–22 bp long and has characteristics 2 nt 3’ overhangs which helps them to be recognized by the mechanism of RNAi.

Targeting and manipulating RNAi pathways can be a potential tool to change any biological process post-transcriptionally in many health conditions including g autoimmune diseases and cancer among others. RNAi was described as “Breakthrough of the year” by the journal Science in the year 2002, having the potential to be a powerful drug for several diseases. Optimum designing of siRNA can enhance the stability and specificity of the RNAi process and prevent off-target effects.

Design:

When considering siRNAs for therapeutics, it is essential for the selection of appropriate designs that have good potency, stability, and specificity. Over the years, protocols have been put in place to assist in designing an ideal siRNA, based on the target of interest. Once synthesized these siRNAs should be experimentally evaluated to determine its effects in gene silencing. Though tested to be effective, at times siRNAs have off-target effects, where unrelated genes tend to be altered. Furthermore, siRNAs may also induce an unnecessary innate immune response which could potentially initiate a harmful inflammatory response in patients.

Stability:

When using siRNA technology for therapeutics in in-vivo models, the stability of the molecule plays an important factor. When unprotected, siRNA is highly unstable and can easily be degraded in the human plasma, with very minimal half-life. At times like these, siRNA is chemically modified to increase the half-life without altering the efficacy. Such chemical modifications usually happen in the phosphate group of the molecules hat confers exonuclease resistance or alterations in the sugar residues that confer endonuclease resistance. A right balance between increased stability and efficacy is the right way to configure a siRNA for in-vivo use.

Delivery:

It is safe to say that no matter the efficacy or stability it is most challenging to deliver the right siRNA to the targeted tissues/ cells. Due to its negative charge, siRNA molecules are incapable of penetrating cell membranes easily. For this reason, many strategies have been developed like lipid-based formulations. Most of these strategies are non-specific and are build into delivery agents.

Recently, study results showed that single-stranded siRNA is capable of performing gene silencing in-vivo. This finding is particularly significant since single-stranded siRNA has multiple advantages over double-stranded siRNA. The lack of second passenger strands makes it more potent and reduces the risk of uncalled alterations.

Applications in medicinal fields:

Due to the effective gene silencing, siRNA is popular among medicinal fields. The degree of specificity is also an added advantage, as is its ability to utilize numerous RNA sequences to target specific cells and deliver drugs or medicines. The ultimate goal for scientists is to find an optimal way to kill or slow down the disease without affecting the surrounding tissues. In addition, the ability to specifically target genes that cause cellular damage or destruction enables pharmaceutical experts to specifically target those genes by the use of siRNA interference.

The progression from the initial discovery of siRNA technology to clinical applications has been groundbreaking. Understanding the fundamentals behind the technology has led to its widespread application in both basic research and clinical applications of treating a disease.

Despite the significant progress made in the field of RNAi technology, there is still a lot of more research that needs to be conducted to perfect the design Before siRNA becomes a common commercial therapeutic technology in the clinical field, a number of major hurdles need to be addressed. Lately, the difficulties associated with inefficient delivery to target cells have been brought into the light. There are also problems associated with the reduced biostability of unmodified RNA.

Regardless of certain setbacks, the hope still remains that with the time, siRNA technology will prove to be the next “Superdrug” against many destructive diseases. In addition, RNAi has proven to be an important tool and has opened a new world of basic investigation.

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Jul, 2020

Exploring CAR-T-cell therapy using CRISPR technology

Immunotherapy is the lesser-known mainstream treatment for cancer. It has recently been gaining popularity ever since the first chimeric antigen receptor T- (CAR-T) cell therapy was approved for Non-Hodgkin lymphoma in 2017. Currently, numerous CAR-T-cell therapies for a variety of cancers are being granted investigational new drug clearance to enter clinical phases.

The clustered short palindromic repeat or also known as CRISPR associated protein 9 (CRISPR/Cas9) technology plays a crucial role in advancing the CAR-T-cell therapy field, owing to its high efficiency, simplicity, and flexibility. It is an exciting new world out there for CAR-T cell therapy researchers, aiming to term cancer a curable disease.

What is chimeric antigen receptor T- (CAR-T) cell therapy?

CAR-T cell therapy usually involves engineered T cells that act as synthetic receptors. They typically contain a tumor-specific chimeric antigen (CAR) containing an intracellular domain, an antibody derived targeting extracellular domain and transmembrane domain. The transmembrane domain from CD28 is responsible for providing stability to CAR.

The T cells programmed with CARs can be used to specifically target and kill antigen-expressing cells without the major histocompatibility complex. Data from studies show that CAR-T-cell therapy has helped in the complete remission of patients diagnosed with a variety of solid and hematologic cancers, especially in relapsing cases of acute lymphoblastic leukemia with a remission rate of 80-100%.

CRISPR technology in developing CAR-T-therapy:

One of the crucial decisions in designing CAR-T cells is choosing the right DNA template for CAR expression. An appropriate DNA template should be obtained easily and rapidly, containing flexible insert sizes, highly efficient target sites, and low cellular toxicity. For a long time, viral vectors were used, but concerns regarding the integration in the wrong location causing unnecessary diseases, gave rise to CRISPR/Cas9 technology.

A powerful eukaryotic cell genome editing tool, CRISPR/Cas9 technology makes it possible to insert large genes at the required genetic sites in T cells for successful CAR-T engineering without viral vectors. The two essential components of CRISPR technology include a guide RNA (gRNA) customized to recognize the protospacer on target DNA, and a Cas9 protein to create precise double-stranded breaks (DSBs) for gene mutation.

DSBs have a unique ability to create two distinct mechanisms for repair. One is through the non-homologous joining, which introduces mutations to DSB sites and the other a homology-directed repair (HDR) mechanism which makes sure the donor DNA template is accurately placed for the gene knock-in. The HDR mechanism is popular among researchers due to its precision insert of the CAR expression cassette into the T cells.

Methods employed to prevent allogeneic CAR-T side effects:

The multigene editing capability of CRISPR/Cas9 technology is employed for the potential safety of any allogeneic CAR-T therapy-associated side effects. For example, to prevent any graft Vs host rejection, the general approach would be to knock out the expression- TCR-αβ of T cells. To function, TCR-αβ requires both α- and β-chains. The α-chains encoding TCR-α can be knocked out using CRISPR gRNA. From previous studies, it can be noticed that when CAR placed under endonuclease transcriptional regulation, it leads to continued T cell function and a delay in cell exhaustion.

Host Vs graft disease can also be avoided by knocking out β2-microglobulin, an essential part of the major histocompatibility complex class I molecules, using CRISPR to stop the surface antigen presentation. The gRNAs have also been shown to target immune inhibitory receptors enhancing the antitumor activity of CAR-T-cells.

Future Perspective:

The remarkable use of CAR-T cells in the remission of advanced malignancies is promoting the rapid growth in developing smarter and commercialized CAR-T therapies. The CRISPR/Cas9 genome editing technology promises a hopeful next-generation CAR-T cell product by adding novel CAR-T cells knockout and inducible safe switches to avoid self-killing.

However, there are certain concerns regarding the technology which includes off-target effects, causing random mutations. Multiple strategies such as optimized gRNA design, careful selection of target sites, prior off-target detection assays should be attempted to minimize the risks.

By technical progress to avoid mutations, and improved delivery efficiency, CRISPR/Cas9 mediated T cell engineering holds great promise. Currently, experts are working on exploring other CRISPR/Cas 9 gene targets for multiplex editing for potentially developing an optimal off-shelf allogeneic CAR-T cells products as universal treatment options.

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Jul, 2020

Versatile use of Bacterial nanocellulose for wound healing applications

Over the years, several therapeutic options have been available for wound and burn treatment. The urgent need for better strategies to accelerate treatment leaves more scope for therapeutic improvement in this field.

Cellulose is one of the most naturally occurring polymers from renewable sources. Occurring in the form of a linear homo-polysaccharide it consists of β‐d‐glucopyranose units linked by β‐1,4 glycosidic bonds. In modern times, bacteria is one of the commonly used sources for producing cellulose also known as bacterial cellulose. Recently, experts have been playing around with the idea of bacterial Nanocellulose (BNC), cellulose constructed using nano-engineering.

Bacterial nanocellulose matrix has outstanding mechanical and physical properties courtesy of its unique 3D structure. BNC aggregates to form long fibrils, providing room for high elasticity, surface area, and resistance. Such intrinsic characteristics make it the best choice for wound dressings or protecting injured tissues. It does help that BNC is also non-carcinogenic, non-toxic, and biocompatible.

Bacterial nanocellulose in wound healing:

It is well known that the largest organ of the body is skin. In its native state, the skin is usually dry and acidic in nature. Altered skin integrity is usually caused by systemic factors such as nutrition, among others. When an individual suffers from serious skin damage due to an accident or disease, a complex series of the biological processes are involved in restoring the lost skin.

A perfect wound dressing must be able to retain moisture and allow oxygen exchange accelerating healing time and preventing infection. Experts consider BNC to be one of the most suitable materials for wound treatments due to its characteristics such as favorable mechanical properties, chemical purity, and water-absorbing capacity. BNC in its natural state has consistently shown great capacity to stimulate wound healing. To further improve the healing effect of BNC, the material can be combined with natural additives such as proteins, glycosides among others, to improve the mechanical strength and cellulose-based dressings with antimicrobial properties.

Incorporating mesenchymal stem cells into bacterial nanocellulose:

One of the recent strategies to improve BNC wound dressing is the incorporation of mesenchymal stem cells (MSC) in the matrix. MSCs are adult pluripotent stem cells that are expected to integrate into the victim’s tissue and promote regeneration of the damaged tissue.

Several studies prove that MSC can evolve into various cell types including muscle bone and cartilage. They have a great capacity to self-renew while maintaining its integrity, an essential feature needed to improve the wound healing process, and inducing re-epithelization of the wound.

Genetically engineered bacterial nano cellulose:

Genetic engineering of the BNC is currently being explored with an aim to optimize the properties of the matrix and the cost-effectiveness of the manufacturing process. Previously, strain improvement was performed through the transfer of BNC related gene determinants to a previously prepared “cell factory” organism. This was done to produce a heterologous expression of genes.

Recently a study used a small RNA (sRNA) interference system to improve the native cellulose production path. The constitutive production of the BNC was shut off to prevent any mutants, a common phenomenon in a well-aerated environment. This was replaced by expression vectors to functionalize BNC with specific proteins, by fusing the genes encoding the protein of interest to the short nanocellulose binding domains.

Challenges and Future Directions:

Using nano engineering in the field of tissue engineering has opened up a lot of new prospects. Experts are looking to develop BNC based out of commercial 3D printing materials, as an alternative to the chemical products such as resins, synthetic thickeners, and plastics, Another added advantage of 3D printed BNC is the possibility of creating flexible and adjustable dressings. The option of 3D printed nanofiber based bacterial cellulose can also offer an opportunity to develop wearable biomedical devices as sensors and drug-releasing materials, to monitor the patient’s wounds constantly.

Another interesting discovery on the works is the creation of transparent wound coverings using nanocellulose. This discovery will allow optical real-time monitoring of wound healing and help in diagnostics of viral infections and inflammations in chronic wounds.

In conclusion, although BNC has made substantial progress in the field of tissue engineering, one of the common drawbacks is the non-degradability of nanocellulose in human organisms. This could potentially lead to scar formations and other complications when intended for direct use. However, artificially constructed skin can be used for experimental studies, such as metabolism, and vascularization of skin tissue.

Currently, there are no materials yet to be found that can fully capture the intricates of the native tissue to restore function at an ideal level. The remaining challenge will be to innovate new composite materials using nanoscale engineering to produce fully biomimetic tissues. As the complexity of applications increase, an active remodeling of the existing scaffolds will be required.

Source

Jun, 2020

COVID 19: A battle between heat and humidity Vs Sunshine

Though some experts suggest that heat and humidity can help in slowing down COVID-19, others argue that long hours of sunshine can risk a higher incidence of the disease. Let’s investigate further.

With the deadly COVID-19 affecting the economy all over the world, lockdowns are slowly being lifted to compensate for the damage. People are slowly crawling back to public places like the beaches and soaking in the much-needed vitamin D from sunshine. But there is a price to pay.

A sign of a sunny day attracts many people to go out, in turn increasing the risk of infection due to a lack of social distancing. Experts speculate long exposure to sunlight also poses a high risk of contracting the virus. While on the other hand, reports state that heat and humidity can potentially slow down the spread of COVID-19.

A recent report published in the journal Geographical Analysis gives insights on how seasonal changes influence the spread of the novel virus.

Temperature a crucial factor:

For several weeks now, research has been conducted revolving around the effect of temperature and humidity on COVID-19. Several experimental studies explain that it is possible for the COVID-19 virus to be sensitive to heat and humidity, and with further study, experts are convinced that the rate at which the virus spreads can vary in places with different temperatures and humidity.

Studies reveal that humidity and temperature may make the COVID-19 virus less viable by disrupting their surface proteins and outer membranes. On the other hand, the change in infection rate might differ due to the ways people change their behavior from being enclosed in spaces to spending more time outdoors. But currently, there is no solid proof to confirm that summertime can bring improvement in this current pandemic.

Not all Pandemics or diseases follow the same seasonal patterns seen more commonly in seasonal flu outbreaks. Spanish flu, for example back in 1918, peaked during the summer months, while most of the common flu outbreaks erupt during winter.

COVID-19:

At high levels of humidity and heat, the authors of this study noticed a steady decline of 3% in the confirmed COVID-19 cases, possibly due to the virus dying under warmer temperatures. The opposite was observed at long exposure to the sun. More the sunshine more the rate at which the virus spread, raising concerns if it’s due to the human behavior post lockdown measures.

The authors of the study stated that “We will likely see a decrease in the incidence of COVID-19 as the weather warms up, which is an argument for relaxing social distancing to take advantage of the lower incidence associated with higher temperatures” he says. “But a more conservative approach would be to use the months of summer to continue to follow strict orders to remain in place and to crush this pandemic.”

Source

Jun, 2020

COVID-19: Loss of smell, a new symptom added to the list

New evidence finds that anosmia- loss of smell as a new symptom caused by the COVID-19 virus. Experts believe that it can be added as a potential screening tool for the novel viral infection, and here’s why!

Cases of post-viral anosmia are one of the leading causes of loss of smell among adults suffering from viral infection. This has been associated with previous coronaviruses which are usually known to cause upper respiratory tract infections and have accounted for 10-15% of the cases. Therefore it comes off as no surprise that the current novel COV ID-19 virus also causes anosmia in the infected.

A significant number of cases from South Korea, Italy, and China prove as good evidence for COVID-19 patients developing anosmia. More than 2 out of 3 confirmed cases in Europe have been diagnosed with anosmia. It is also noticed that several COVID-19 cases also present anosmia as the only symptom. Given the above evidence, experts contemplate using anosmia of a screening tool to diagnose people with COVID-19 at the early stages.

Cases of anosmia reflect how COVID-19 affects the brain:

“There’s something unusual about the relationship between COVID-19 and smell,” states Sandeep Robert Datta a neuroscientist from Harvard Medical School and one of the leading scientists in the study. It is well known that common cold, is associated with stuffy noses leading to a temporary loss of smell, but it found that the COVID-19 virus leaves the nose free. “But recently lots of people are complaining about losing their sense of smell when they don’t feel stuffed up at all,” Datta says.

The team further experimented on nose cells, including the support cells and nerve cells sending messages to the brain using both mice and human models. This was especially performed to see if there were any signs of a link between the cells and the ACE2 receptor. A small recap: ACE2 receptor is the primary receptor in humans which the COVID-19 viruses used to attach to the host and cause infection.

The researchers from the study found that the results demonstrated a molecular signal showing that ACE2 receptors were present in nose cells and the subsidiary cells. These cells generally maintain a chemical balance in the nose, which allows the nerve cells to send smell signals to the brain.

A Contradicting study published by a team from Nicolaus Copernicus University, Poland resulted that the olfactory neurons did not pose any ACE2 receptors, implying that the novel virus cant infect the cells themselves.

It was also noticed that the timing of the onset of anosmia symptoms was varied, with some patients developing the symptoms at early stages, while another group of patients reported the loss of smell in the later stages of their illness.

How will this help in the fight against COIVD-19?

More studies need to be conducted regarding the frequency of the symptoms and the exact science behind how the COVID-19 virus affects the olfactory senses. To collect more data on the cases posing these symptoms, the AOS-HNS Infectious Disease and Patient Safety Quality Improvement Committees have developed a COVID-19 anosmia detecting tool for health care workers. Using this tool the clinicians of all specialties will be able to confidently confirm cases portraying the loss of smell.

The idea of adding the symptoms of unexplained anosmia as an official symptom of COVID-19 can help with earlier detection and isolation of potential carriers of the virus and improve safety by containing the spread of the virus.

Source

Jun, 2020

COVID-19 patients with hypertension have more severe disease: a multicenter retrospective observational study

Late last year, a number of unexplained pneumonia cases surfaced in Wuhan, China. Later scientists revealed that it is caused by a familiar group of pathogens, coronavirus. The WHO later named this virus, COVID-19. The virus is highly contagious, infecting millions in the last couple of months.

From previous studies, it is considered that angiotensin-converting enzyme (ACE2) is the receptor for the COVID-19 virus to enter the host cell. ACE2 is a widely expressed receptor in several organ systems of the human body, including cardiovascular and respiratory systems. The enzyme helps in catalyzing angiotensin II to angiotensin 1-7, which is the peptide counteracting proinflammation caused by Angiotensin II.

Studies have proven that hypertension is a common condition that co-occurs in patients with COVID-19. A previously conducted study, involving 1099 COVID-19 patients reported that 23.4% of the population also suffered from hypertension. Due to the coexisting status of hypertension and COVID-19 and the involvement of ACE2 in hypertension, the authors of this study speculate that hypertension may directly be involved with the pathogenesis of COVID-19.

To confirm if hypertension affects the progress and prognosis of COVID-19, the published study was conducted. The study involved 310 patients from the Central Hospital of Wuhan and Wuhan Jinyintan Hospital. All the participants according to the WHO were tested positive for COVID-19. The study was later divided according to high blood pressure (hypertensive and non-hypertensive group). To avoid unwanted complications, the hypertension group was further segregated to exclude patients with other complications other than hypertension.

All the participants were monitored closely and the entire course of the disease was recorded. The median age of the participants in the study was 62 years and the prevalence rate of hypertension was 36.5%. The authors speculate that the high prevalence rate of hypertension in the study group could be due to the high median age. The study also revealed that COVID-19 patients with high blood pressure showed higher mortality.

Evidence suggests that an imbalance of cytokines could be a possible correlation between COVID-19 and hypertension. An increase in cytokines like IL-6, IL-7, and tumor necrosis factor is associated with the development of hypertension. It should also be noted that the increased levels of cytokines, may potentially activate excessive inflammatory reactions, resulting in cell and lung damage.

Overall the comparative study conducted using COVID-19 patients with and without hypertension showed that patients who were hypertensive were more likely to be severely affected with COVID-19 compared to the non-hypertensive group. It must be brought to light that there might be a small number of people with hypertension not recorded because the diagnosis of hypertension in this study was extracted from medical history data.

Finally, the authors conclude that much larger groups need to be studied since the current result could be due to the higher aged participants. In the future, additional complications also need to be analyzed like ARDS, renal injury focusing on its risks associated with hypertension and COVID-19.

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Jun, 2020

Risk Factors and Biomarkers of Ischemic Stroke in Cancer Patients

Numerous types of cancer are associated with ischemic stroke and are popularly known to be co-morbid conditions. They are two of the most frequent causes of death among the elderly population. A previous report of autopsies on cancer patients indicated that around 7.4% of the population suffered from stroke symptoms. With further analysis it was noticed that about 3.5% of the cancer patients were paralysed from strokes.

The causes of ischemic stroke in cancer and non-cancer patients are highly different. Reports suggest, most of the cancer patients suffer from stroke mainly due to hypercoagulation. The blood clot formed restricts the blood flow to the brain, causing the cells in the brain to perish. This in turn paralyses the parts of the body controlled by the dead cells. While on the other hand, some reports suggest that stroke and cancer pathogenesis may be due to coagulopathy and atherosclerosis. The aim of this study is to study ischemic stroke in cancer patients using relevant biomarkers and compare it with non cancer patients with stroke.

The study involved cancer patients with ischemic stroke from General Hospital in Busan, Korea. All the patients had active cancer with an onset of stroke symptoms. The control group used were patients from the same hospital, non cancer patients suffering from ischemic stroke. For examining the biomarkers, patients’ blood was collected and serum was assessed.

The study found that biomarkers such as D-dimer levels, erythrocyte sedimentation rate (ESR), fibrinogen and Brain natriuretic peptide (BNP) were significantly higher in the cancer patients when compared to non cancer patients with stroke.

D-dimer are one of the basic bio-markers for stroke due to their discovery as by-products of fibrinolysis. As a fibrin degradation product, dimer is directly associated with coagulation and plays a major role in hypercoagulation. Compared to non cancer ischemic stroke patients, D-dimer levels were found to be higher in cancer patients diagnosed with stroke.

Blood coagulation in cancer patients is activated by inflammation. In this study, the authors used ESR, because of its well known use as a marker for infection and inflammation. An increased level of ESR indicating fibrinolysis was noticed in cancer stroke patients when compared to the control group.

From previous papers, it is well known that fibrinogen plays a major role in inflammation and platelet aggregation. An increase in fibrinogen is directly associated with increased risk of stroke in patients. In the current study cancer patients with ischemic stroke had a significant increase in fibrinogen than non cancer patients.

Cancer patients with ischemic stroke portrayed high levels of stroke biomarkers when compared to the non cancer patients with ischemic stroke- control group. The above results showcase a strong relationship between the cancer patients and conditions like hypercoagulation and inflammation, which could possibly explain the frequency of paralysis in aged cancer patients leading to death. Therefore, in order to reduce any incidence of ischemic stroke in cancer patients, doctors should focus on reducing inflammation and platelet coagulation.

Source

Jun, 2020

Why does your scientific writing need to be clear and precise?

Scientific writing is not just something used to talk about science, but a form of technical writing that experts and scientists use to explain and communicate their research to the world. A good piece of scientific writing should maintain the same clarity and precision of that used in research work. In communication between the author and the audience, scientific writing demands precision- a precise use of words and phrases, and most important clarity.

All the above three criteria are crucial because of the highly technical terms and phrases used by the author to represent his/her work especially to an audience with very less or no knowledge on the subject. It must be acknowledged that sometimes the audience might be from a different discipline and may not be a native speaker of the language used in the writing.

Due to the vast number of audiences which a journal attracts, it is important to keep the work as precise as possible which helps in preventing any mistranslations and misunderstandings. It is also essential to portray communicating figures, and facts used in research as well as the description of results, precise and exact.

What does it mean to be clear and precise in scientific writing?

A key to any writing is to focus on words and punctuation. Subtle differences in the word choice or correct use of punctuation can significantly elevate ones writing.

An organization of writing is crucial. The paper should be telling a story, making it logical, with specific rules going into each section. In academic wiring, your work needs to be unambiguous and accurate. Though not as simple as it sounds,

it will help in making it more readable to the audience. Writing precisely requires careful thinking and editing. If a person has to work too hard to comprehend what he reads, then a problem persists in the authors writing skills.

Remember you’re not trying to impress, you’re are writing to communicate.

If you want your work to be read, you as an author should do most of the work for the audience, and a key important part of this is implementing a flow in your writing.

What strategies to use in scientific writing?

When writing your piece, you should be clear in the information you are providing. The key to any great writing is its structure. For example, if you are covering three different topics in a paragraph and don’t give a coherence, then the reader will not be able to comprehend and find it hard to read.

Another crucial guideline to achieve flow is to always provide ample information to your audience so that each sentence is lucid. Every sentence provided by you as an author should comprehend each other. This can be achieved by providing information or referring to the previous sentence before introducing new information. Below are some pointers:

Using effective transitions between paragraphs, sections, and within sentences when applicable.

Writers are recommended to start their sentences using strong verbs and nouns, and not use weak phrases.

Always strive to have clarity in your writing, try to make the unspoken spoke. Just because a sentence or piece of information is comprehensible by you as a writer doesn’t mean your audience is on the same wavelength as you are.

There is always a point of exhaustion an author reaches. At times like this, try to take the break you need, step away from your writing and have a look at it again from a fresh perspective. This will not only help you rectify your mistakes but also helps you view your work from a reader’s point of view.

Why is it so important to maintain a standard in scientific writings?

In the field of science, good writing skills is not a luxury, but a much-needed skill. It is fundamental to spread knowledge, but also for creating knowledge among the audience. During the writing process as an author, we are forced to keep things precise and simple. It is by our writing that we bridge the gap with respect to the lack of clarity or information. According to the great philosopher Artur Schopenhauer

“Unclear writing is an indication of unclear thinking”

If an author cannot concisely, clearly, and logically represent his collected and analyzed data, it doesn’t matter even if its groundbreaking discovery, the reader will not be able to understand and question your results. So it should be really stressed that the clearer authors explain their work, the better understood by more number of people.

May, 2020

Adapting to survive: How Candida overcomes host-imposed constraints during human colonization

The human body is well known to host a large number of microbes, mostly harmless but when triggered might turn virulent. A large fungal ecosystem resides inside a human body mainly including Candida species, constituting a large part of the human body’s microbial flora. Usually asymptomatic, Candida forms small colonies, but when triggered such as environmental change, can potentially help the microbes to break barriers and cause life-threatening diseases.

Though multiple numbers of antifungal drugs are available, it is recently found that Candida species is capable of building resistance against the drugs by forming biofilms. The article further talks about the environment within the host body paving way to such resistance.

Within the human host, Candida is capable of changing morphology and functions according to the change in the environment it resides in. Several factors play a role including temperature, ph, and oxygen supply. Candida depending on the environment can take forms such as hyphae, budding, or even pseudohyphae.

Another crucial role played in a microbial existence within the human host is nutrients availability. It is reported that microbes thrive in the area of high glucose content. When deprived of glucose is when microbes turn to another source of nonfermentable nutrients. Research performed in labs using Candida flora has reported that in the presence of glucose the microbe is known to morph into hyphae and promote antifungal resistance.

The limitations of micronutrients such as iron magnesium, and copper are known to limit the growth of invading microbes. But this is quite tricky as micronutrients are needed both by the host and microbes in functioning such as biochemical and cellular functions.

It is very well known that oxygen and ph levels vary within every niche in the human body. While some are alkaline and high on oxygen concentration others are hypoxic and acidic. Candida microbes being versatile they are, can adapt their cell walls according to the change in ph. It is also interesting to note that Candida microbes thrive under hypoxic conditions, inducing their hyphal growth and causing immune evasion.

The above has described the flexibility of the microbes to overcome multiple constraints faced in the host body. This ability of Candida helps it to form colonies and invade niches around the body. Another strategy imparted by the microbes is biofilm formation against the host body or biomedical devices. Biofilms consist of a 3D community of adherent cells with different biological properties. These cells are embedded in the ECM, which helps in maintaining the overall integrity of the biofilm. The ECM also acts as a protective barrier against any drug invasion. These features play a crucial role in Candida microbes resistance against antifungals and biomedical devices.

With the emergence of resistant Candida species, the need to develop new antifungals is inevitable. Research using an in vivo model to mimic the host conditions is giving close insights to unravel the mysteries of the microbes. These approaches are paving the way to novel therapeutic vaccines and anti-fungal treatments, enhancing the body’s ability to fight off the infections.

Source

May, 2020

Artificial intelligence-enabled rapid diagnosis of patients with COVID-19

Since December 2019, multiple cases of pneumonia due to unknown reasons have emerged in Wuhan, China. Through testing multiple patient samples, scientists extrapolated a new coronavirus termed COVID-19. With no FDA approved therapeutics or treatment available for the disease, diagnosis plays an important role in containing COCVID-19, giving a path to the rapid implementation of control measures to limit the spread. With the disease spreading to almost 100 countries, a million cases have been confirmed worldwide to date. Imaging is one of the main principles used in diagnosing and evaluating the disease, with the final diagnosis depending on reverse transcriptase-polymerase chain reaction (RT-PCR).

In response to the growing number of COVID-19 cases, there is currently a shortage of diagnostic kits worldwide. Multiple industries are coming forward to develop rapid, easy to use diagnostic kits to facilitate testing. However before these kits can be commercialized, they must be tested and validated. With the current available tests taking almost 2 days to complete and produce a result, serial testing is required to rule out any negative cases. Additionally, it is a mystery as to whether an RT-PCR is a gold standard and whether a false positive/ negative result is common. The above reasons highlight the need for alternative testing methods to produce rapid and accurate results to identify, isolate, and treat the affected people.

Chest computed tomography is also a much-used valuable component in testing COVID-19. With some of the patients showing early-stage symptoms in radiological finding, limits the CT ability to differentiate between a positive and negative case. In this current study, the authors have used Artificial Intelligence (AI) algorithms to help in integrating CT scanning in finding the symptoms of the virus, exposure history and reliable lab testing to rapidly diagnose the patients affected with COVID-19.

A trial was performed on 905 patients diagnosed using RT-PCR and next-generation RT-PCR and around 46% (419) people were declared positive for COVID-19. Parallelly in a test set of 279 participants, the AI system managed to achieve accuracy to about 92% of the population and had equal or even better sensitivity than a senior radiologist. The AI system also improved the detection of COVID-19 positive patients with negative CT scans, identifying 17 out of 25 participants who were tested positive via RT-PCR but negative with normal CT scans. In comparison, the radiologists’ declared the said 17 participants to be COVID negative.

AI shows signs of analyzing huge amounts of data quickly, a quality that is much needed in the current pandemic. A major limitation of the above study is the small sample size, with available CT scans and clinical history data, the AI system can help in diagnosing COVID-19 patients rapidly. Though a promising tool, further data collection is required to test the generalization of AI mapping on other patient populations.

Source

Author: Swati Pal

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