Neuralink and Brain-Computer Interface-Exciting Times for Artificial Intelligence.

Purvish Mahendra ParikhBrain-computer interfaces are becoming a tangible reality, capable of significantly aiding patients in real-world scenarios. The recent approval by the U.S. Food and Drug Administration for clinical human trials of Neuralink marks a monumental stride, comparable to Mr. Armstrong's moonwalk. Numerous other companies are also pioneering innovative solutions in this domain. Presently, over 150,000 patients in the United States possess brain implants. As technology advances, it holds the potential to alleviate various conditions, notably motor paralysis, cerebral palsy, and involuntary movements.

The Troubling Link Between Non-alcoholic Fatty Liver Disease (NAFLD) and Extrahepatic Cancers (EHC).

Non-alcoholic fatty liver disease (NAFLD) is a fast-spreading epidemic across the globe and has serious implications far beyond that of a "benign" liver condition. It is usually an outcome of ectopic fat storage due to chronic positive energy balance leading to obesity and is associated with multiple health problems. While association with cardiovascular disease and hepatocellular cancer is well recognized, it is becoming clear the NAFLD carries with it an increased risk of cancers of extrahepatic tissues. Studies have reported a higher risk for cancers of the colon, breast, prostate, lung, and pancreas. Fatty liver is associated with increased mortality; there is an urgent need to understand that fatty liver is not always benign, and not always associated with obesity. It is, however, a reversible condition and early recognition and intervention can alter its natural history and associated complications.

Synergism between anti-angiogenic and immune checkpoint inhibitor drugs: A hypothesis.

Hepatocellular cancer (HCC) and renal cell cancer (RCC) are singularly resistant to conventional chemotherapy drugs but therapies targeting the supporting stroma have significantly altered their management. Two recent trials combining anti-angiogenic (AA) agents with immune checkpoint inhibitors (ICIs)- the IMbrave150 and IMmotion151 - have reported impressive progress over targeted agents. It has been suggested that bevacizumab, by improving tissue perfusion, changes the immune suppressive tumour microenvironment to an immune stimulatory one where the ICIs can be more effective. This hypothesis proposes an alternative explanation: That bevacizumab, by increasing tissue hypoxia, amplifies the mutational burden of the tumour by stress-induced mutagenesis, creating a hypermutator profile, which is more vulnerable to the ICI drug, atezolizumab. Additionally, ICIs are known to cause hyperprogression in some tumours, and bevacizumab could provide further benefit by starving these rapidly proliferative tumours of blood supply and nutrients.

Corrigendum: PTEN: A Thrifty Gene That Causes Disease in Times of Plenty?

[This corrects the article DOI: 10.3389/fnut.2020.00081.].

PTEN: A Thrifty Gene That Causes Disease in Times of Plenty?

The modern obesity epidemic with associated disorders of metabolism and cancer has been attributed to the presence of "thrifty genes". In the distant past, these genes helped the organism to improve energy efficiency and store excess energy safely as fat to survive periods of famine, but in the present day obesogenic environment, have turned detrimental. I propose PTEN as the likely gene as it has functions that span metabolism, cancer and reproduction, all of which are deranged in obesity and insulin resistance. The activity of PTEN can be calibrated in utero by availability of nutrients by the methylation arm of the epigenetic pathway. Deficiency of protein and choline has been shown to upregulate DNA methyltransferases (DNMT), especially 1 and 3a; these can then methylate promoter region of PTEN and suppress its expression. Thus, the gene is tuned like a metabolic rheostat proportional to the availability of specific nutrients, and the resultant "dose" of the protein, which sits astride and negatively regulates the insulin-PI3K/AKT/mTOR pathway, decides energy usage and proliferation. This "fixes" the metabolic capacity of the organism periconceptionally to a specific postnatal level of nutrition, but when faced with a discordant environment, leads to obesity related diseases.

The most important questions in cancer research and clinical oncology-Question 2-5. Obesity-related cancers: more questions than answers.

Obesity is recognized as the second highest risk factor for cancer. The pathogenic mechanisms underlying tobacco-related cancers are well characterized and effective programs have led to a decline in smoking and related cancers, but there is a global epidemic of obesity without a clear understanding of how obesity causes cancer. Obesity is heterogeneous, and approximately 25% of obese individuals remain healthy (metabolically healthy obese, MHO), so which fat deposition (subcutaneous versus visceral, adipose versus ectopic) is "malignant"? What is the mechanism of carcinogenesis? Is it by metabolic dysregulation or chronic inflammation? Through which chemokines/genes/signaling pathways does adipose tissue influence carcinogenesis? Can selective inhibition of these pathways uncouple obesity from cancers? Do all obesity related cancers (ORCs) share a molecular signature? Are there common (over-lapping) genetic loci that make individuals susceptible to obesity, metabolic syndrome, and cancers? Can we identify precursor lesions of ORCs and will early intervention of high risk individuals alter the natural history? It appears unlikely that the obesity epidemic will be controlled anytime soon; answers to these questions will help to reduce the adverse effect of obesity on human condition.

Minocycline Improves the Efficacy of EGFR Inhibitor Therapy: A Hypothesis.

Skin rash is a side effect of drugs that inhibit epithelial growth factor receptor (EGFR) as a part of targeted therapy of cancer. Its appearance and severity correlates with survival. Minocycline, an oral tetracycline antibiotic, is recommended as treatment (and increasingly, for prevention) of the rash, though infection is seen in only one-third of the patients. Minocycline has additional anticancer properties such as poly(ADP-ribose) polymerase inhibition. It is proposed that such properties contribute to the efficacy of EGFR inhibitors and can also explain the positive correlation between grade of rash and survival as patients with higher grades of rash are more likely to receive minocycline. Early concurrent administration of minocycline is recommended in patients planned for EGFR therapy while awaiting trials proving this hypothesis.

High Occurrence of Non-Clear Cell Renal Cell Carcinoma in Oman.

It is conventionally accepted that renal cell carcinoma (RCC) occurs in older patients and the clear cell type is the most common histology. However, ethnic variations exist and this study was carried out to determine the epidemiological pattern of RCC in Oman. Ninety RCC patients who presented to a tertiary care center in the Sultanate of Oman from 2010 to 2014 were studied. The main findings were that the median age of presentation was low, more patients presented with localized stage, and there was a higher incidence of non-clear (especially papillary) histology. Data from other Gulf countries and possible reasons for the different profile are discussed.

Prostate cancer is not breast cancer.

Cancers of the prostate and breast are hormone dependent cancers. There is a tendency to equate them and apply same algorithms for treatment. It is pointed out that metastatic prostate cancer with bone-only disease is a potentially fatal condition with a much poorer prognosis than metastatic breast cancer and needs a more aggressive approach.