Unpacking Large Language Models with Conceptual Consistency

If a Large Language Model (LLM) answers "yes" to the question "Are mountains tall?" then does it know what a mountain is? Can you rely on it responding correctly or incorrectly to other questions about mountains? The success of Large Language Models (LLMs) indicates they are increasingly able to answer queries like these accurately, but that ability does not necessarily imply a general understanding of concepts relevant to the anchor query. We propose conceptual consistency to measure a LLM's understanding of relevant concepts. This novel metric measures how well a model can be characterized by finding out how consistent its responses to queries about conceptually relevant background knowledge are. To compute it we extract background knowledge by traversing paths between concepts in a knowledge base and then try to predict the model's response to the anchor query from the background knowledge. We investigate the performance of current LLMs in a commonsense reasoning setting using the CSQA dataset and the ConceptNet knowledge base. While conceptual consistency, like other metrics, does increase with the scale of the LLM used, we find that popular models do not necessarily have high conceptual consistency. Our analysis also shows significant variation in conceptual consistency across different kinds of relations, concepts, and prompts. This serves as a step toward building models that humans can apply a theory of mind to, and thus interact with intuitively

Cardiac drugs and outcome in COVID-19

We read with much interest the article “Are certain drugs associated with enhanced mortality in COVID -19” by Goldstein et al your esteemed Journal. Authors have discussed the theoretical basis of angiotensin receptor blockers, statins in worsening outcome of COVID – 19 patients.(1) We believe that this topic is rapidly evolving and requires further evidence and discussion for understanding the multiple factors which contribute to the pathogenesis and outcome. We have the following comments

Evolocumab: rising momentum as novel antidyslipidemic drug

Increased levels of low density lipoprotein cholesterol are responsible for the major cardiovascular events. Low density lipoprotein cholesterol reduction has proved to be highly effective in reducing the risk of major cardiovascular (CV) events in various trials. ACC/AHA guidelines recommend lipid-lowering therapy for patients with known cardiovascular diseases (CVD). Statins are the gold standard treatment for all types hypercholeterolemia but still there is need of some other lipid-lowering therapies especially in patients with statin intolerance and in patients responding inadequately to statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was discovered in 2003 and subsequently emerged as a novel target for LDLC-lowering therapy. Evolocumab is a fully human monoclonal immunoglobulin G2 (IgG2) directed against human PCSK9. Evolocumab binds to PCSK9 enzyme rendering it unable to bind to the LDLR. More LDLR are available to bind to LDLC. Evolocumab increase the density of LDLR on the surface of hepatocytes, thereby increasing the uptake of LDL particles and decreasing the LDLC in the blood. Evolocumab has proved its efficacy with LDLC reduction from 53% to 75% and associated with minor side effects. Evolocumab has corroborated its effectiveness in reduction in the levels of LDLC. This drug has shown efficacy in heterozygous and homozygous subtypes of familial hypercholesterolemia. Statin intolerance seen in about 15% of all patients restricts the use of first line drug for dyslipidemia. Evolocumab can be a useful option in statin intolerant patients and in patients responding inadequately to statins

Phytochemical Screening and Antioxidant Activity of Methanolic Extract of Ocimum Sanctum Linn. Leaves

The phytochemicals present in plants are responsible for preventing disease and promoting health have been studied extensively to establish their efficacy and to understand the underlying mechanism of their action. Such studies have included identification and isolation of the chemical components, establishment of their biological potency both by in vitro and in vivo studies in experimental animals and through epidemiological and clinical-case control studies in man. Study findings suggest that phytochemicals may reduce the risk of coronary heart disease by preventing the oxidation of low density lipoprotein (LDL) cholesterol, reducing the synthesis or absorption of cholesterol, normalizing blood pressure and clotting, and improving arterial elasticity. Phytochemicals may detoxify substances that cause cancer. They appear to neutralize free radicals, inhibit enzymes that activate carcinogens, and activate enzymes that detoxify carcinogens. They observed that, the Ocimum sanctum Linn has also been suggested to possess, anticancer, anti-diabetic, anti-fertility, antifungal, antimicrobial, cardio protective, analgesic, antispasmodic and adaptogenic actions. Eugenol (1-hydroxy-2methoxy-4-allylbenzene) is the active constituents present in Ocimum sanctum Linn. Indian traditional shrub tulsi (Ocimum sanctums): They unique medicinal plant. They observed that, Ocimum sanctum heals many diseases chronically due to its chemical constituent and believes that it has anti- ageing, immunomodulatory property along with antimicrobial and anticancer property. Phytochemical analysis of aqueous extract of Ocimum sanctum. They observed that, the plant is known to possess antiseptic, analgesic, anti-inflammatory, antimicrobial, antistress, immunomodulatory, hypoglycemic, hypertensive and antioxidant properties. The dried powder of Tulsi (100g) was placed in the thimble of Soxhlet apparatus.500 ml of distilled water was used as a solvent

OBETICHOLIC ACID: AN INSIGHT INTO A QUANTITATIVE DETERMINATION AND METHODOLOGICAL VALIDATION THROUGH NUCLEAR MAGNETIC RESONANCE

Objective: The research work unveils the use of nuclear magnetic resonance (NMR) technique for quantitative determination and method validation of obeticholic acid. As standard expository methodology for more up to date medications or formulations may not be available in pharmacopeias, hence it is fundamental need to create novel analytical procedures which should be precise and accurate. Methods: Proton (1H) and carbon (13C) NMR analysis were initially performed to confirm the preliminary authenticity of obeticholic acid API. Method validation was accomplished on the basis of standard guidelines for the parameters, in which tetramethylbenzene as an internal standard and deuterated dimethyl sulfoxide as a diluent were used to assess the obeticholic acid. Results: For the quantification of the drug, the proton nuclear magnetic resonance signals at 0.602 ppm and 6.86 ppm corresponding to the analyte proton of drug and internal standard respectively were used. The curve equation calculated from the regression method, the relative-standard-deviation and correlation-coefficient were found to be 0.743% and 0.9989 respectively, indicating good linearity. Consequently, the quantitative assay of the drug was found to be 99.91% in linearity with limit of detection and quantification values as 0.0773 mg and 0.2344 mg respectively, making successful the study of method validation for obeticholic acid. Conclusion: The advantage of the method was that no reference standard of analyte drug was required for quantification and method validation. The method is non-destructive and can be applied for quantification of drug in commercial pharmaceutical formulation products

Review of clinical profile, risk factors, and outcome in patients with Tuberculosis and COVID -19

Coronavirus disease (COVID 19) has involved millions of people all over the world. Tuberculosis (TB) continues to affect millions of people every year with high mortality. There is limited literature on the occurrence of COVID 19 in patients with TB. We reviewed the available data on various clinical details, management, and outcome among patients with COVID-19 and TB. 8 studies reported a total of 80 patients with this coinfection. These patients were reported from ten different countries, with Italy reporting the largest number of cases. Migrant, males constituted a major proportion of cases. Most reported patients were symptomatic. Fever, dry cough, and dyspnea were the most commonly reported symptoms. Bilateral ground glass opacities were more common in COVID 19 infection and cavitary lesions were more common in patients with TB. Most reported TB patients had been found to have mycobacterium tuberculosis from sputum culture in the background of pulmonary TB. Most patients of TB were treated with multidrug regimen antitubercular therapy. In all 8 studies, COVID 19 was treated as per the local protocol. Mortality was reported in more than 10% of patients. Mortality was higher in elderly patients ( \u3e 70 years) and amongst patient with multiple medical comorbidities

Mechanisms of neurological injury in COVID-19

We read with much interest the article “Neurological Impact of Coronavirus Disease (COVID 19): Practical Considerations for the Neuroscience Community” by Werner et al. published in your esteemed Journal. Authors have described the various neurological details of COVID-19 in detail.1 We believe this topic is important and is continuously evolving. We have the following comments as an addition to the article

Cerebrovascular events in COVID-19 patients

Neurological manifestations in patients with COVID-19 are more frequently being reported. Cerebrovascular events have been reported in around 3% of patients. In this review we summarize the published literature on cerebrovascular events in patients with COVID-19 as available on the PubMed database. So far, 3 studies have reported cerebrovascular events. Cerebrovascular events were identified on screening patients with decreased consciousness or in the presence of focal neurological deficits. These events were common in elderly, critically ill patients and in patients with prior cardio-cerebrovascular comorbidities. The diagnosis of cerebrovascular events was confirmed with computed tomography of the brain in most studies reporting neurological events. Multiple pathological mechanisms have been postulated regarding the process of neurological and vascular injury among which cytokine storm is shown to correlate with mortality. Patients with severe illness are found to have a higher cardio- cerebrovascular comorbidity. With an increasing number of cases and future prospective studies, the exact mechanism by which these cerebrovascular events occur and attribute to the poor outcome will be better understood