Diabetic nephropathy has been the cause of lot of morbidity and mortality in the diabetic population. The renin angiotensin system (RAS) is considered to be involved in most of the pathological processes that result i...Diabetic nephropathy has been the cause of lot of morbidity and mortality in the diabetic population. The renin angiotensin system (RAS) is considered to be involved in most of the pathological processes that result in diabetic nephropathy. This system has various subsystems which contribute to the disease pathology. One of these involves angiotensin II (Ang II) which shows increased activity during diabetic nephropathy. This causes hypertrophy of various renal cells and has a pressor effect on arteriolar smooth muscle resulting in increased vascular pressure. Ang II also induces inflammation, apoptosis, cell growth, migration and differentiation. Monocyte chemoattractant protein-1 production responsible for renal fibrosis is also regulated by RAS. Polymorphism of angiotensin converting enzyme (ACE) and Angiotensinogen has been shown to have effects on RAS. Available treatment modalities have proven effective in controlling the progression of nephropathy. Various drugs (based on antagonism of RAS) are currently in the market and others are still under trial. Amongst the approved drugs, ACE inhibitors and angiotensin receptor blockers (ARBs) are widely used in clinical practice. ARBs are shown to be superior to ACE inhibitors in terms of reducing proteinuria but the combined role of ARBs with ACE inhibitors in diabetic nephropathy is under debate.展开更多
AIM: To compare the utility of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) and Asia-Pacific Association for the Study of Liver (APASL) definitions of acute-on-chronic liver failure (ACLF)...AIM: To compare the utility of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) and Asia-Pacific Association for the Study of Liver (APASL) definitions of acute-on-chronic liver failure (ACLF) in predicting short-term prognosis of patients with ACLF.展开更多
AIM: To systematically review evidence on pathophysiology of intra-abdominal pressure(IAP) in acute pancreatitis(AP) with its clinical correlates. METHODS: Systematic review of available evidence in English literature...AIM: To systematically review evidence on pathophysiology of intra-abdominal pressure(IAP) in acute pancreatitis(AP) with its clinical correlates. METHODS: Systematic review of available evidence in English literature with relevant medical subject heading terms on Pub Med, Medline and Scopus with further search from open access sources on internet as suggested by articles retrieved. RESULTS: Intra-abdominal hypertension(IAH) is increasingly gaining recognition as a point of specific intervention with potential to alter disease outcome and improve mortality in AP. IAH can be expected in at least 17% of patients presenting with diagnosis of AP to a typical tertiary care hospital(prevalence increasing to 50% in those with severe disease). Abdominal compartment syndrome can be expected in at least 15% patients with severe disease. Recent guidelines on management of AP do not acknowledge utility of surveillance for IAP other than those by Japanese Society of Hepato-BiliaryPancreatic Surgery. We further outline pathophysiologic mechanisms of IAH; understanding of which advances our knowledge and helps to coherently align common observed variations in management related conundrums(such as fluid therapy, nutrition and antibiotic prophylaxis) with potential to further individualize treatment in AP. CONCLUSION: We suggest that IAP be given its due place in future practice guidelines and that recommendations be formed with help of a broader panel with inclusion of clinicians experienced in management of IAH.展开更多
Hepatocellular carcinoma(HCC) is primarily a malignancy of the liver, advancing from a damaged, cirrhotic liver to HCC. Globally, HCC is the sixth most prevalent cancer and the third-most prevalent reason for neoplast...Hepatocellular carcinoma(HCC) is primarily a malignancy of the liver, advancing from a damaged, cirrhotic liver to HCC. Globally, HCC is the sixth most prevalent cancer and the third-most prevalent reason for neoplastic disease-related deaths. A diverse array of infiltrating immunocytes regulates the development and progression of HCC, as is the case in many other cancers. An understanding of the various immune components during HCC becomes necessary so that novel therapeutic strategies can be designed to combat the disease. A dysregulated immune system(including changes in the number and/or function of immune cells, cytokine levels, and the expression of inhibitory receptors or their ligands) plays a key role in the development of HCC. Alterations in either the innate or adaptive arm of the immune system and cross-talk between them make the immune system tolerant to tumors, leading to disease progression. In this review, we have discussed the status and roles of various immune effector cells(e.g., dendritic cells, natural killer cells, macrophages, and T cells), their cytokine profile, and the chemokine-receptor axis in promoting or impeding HCC.展开更多
Hepatitis E viral infection has traditionally been considered an acute, self-limited, water borne disease similar to hepatitis A, endemic to developing countries. However, over the past decade, zoonotic transmission a...Hepatitis E viral infection has traditionally been considered an acute, self-limited, water borne disease similar to hepatitis A, endemic to developing countries. However, over the past decade, zoonotic transmission and progression to chronicity in human patients has been identified, resulting in persistently elevated transaminase levels, progressive liver injury and cirrhosis. In addition to liver injury, neurological, renal and rheumatological manifestations have also been reported. Chronic hepatitis E occurs mainly in immunosuppressed individuals such as transplant recipients, human immunodeficiency virus patients with low CD4 counts and in patients with hematological malignancies receiving chemotherapy. Diagnosis is established by persistent elevation of hepatitis E virus RNA in the stool or serum. This population often requires treatment with antiviral agents, particularly ribavirin, as spontaneous clearance with reduction in immunosuppression occurs only in about a third of the patients. The purpose of this review, is to further discuss the clinical presentation, and recent advances in diagnosis, treatment and prophylaxis of chronic hepatitis E.展开更多
The present study highlights the rich species diversity of higher plants in the Bhabha Valley of western Himalaya in India. The analysis of species diversity revealed that a total of 313 species of higher plants inhab...The present study highlights the rich species diversity of higher plants in the Bhabha Valley of western Himalaya in India. The analysis of species diversity revealed that a total of 313 species of higher plants inhabit the valley with a characteristic of moist alpine shrub vegetation. The herbaceous life forms dominate and increase with increasing altitude. The major representations are from the families Asteraceae, Rosaceae, Lamiaceae and Poaceae, suggesting thereby the alpine meadow nature of the study area. The effect of altitude on species diversity displays a hump-shaped curve which may be attributed to increase in habitat diversity at the median ranges and relatively less habitat diversity at higher altitudes. The anthropogenic pressure at lower altitudes results in low plant diversity towards the bottom of the valley with most of the species being exotic in nature. Though the plant diversity is less at higher altitudinal ranges, the uniqueness is relatively high with high species replacement rates. More than 90 % of variability in the species diversity could be explained using appropriate quantitative and statistical analysis along the altitudinal gradient. The valley harbours 18 threatened and 41 endemic species, most of which occur at higher altitudinal gradients due to habitat specificity.展开更多
AIM:To study the seroprevalence of antibody to hepatitis B core antigen (anti-HBc) in healthy blood donors negative for HBsAg and to evaluate whether anti-HBc detection could be adopted in India as a screening assay f...AIM:To study the seroprevalence of antibody to hepatitis B core antigen (anti-HBc) in healthy blood donors negative for HBsAg and to evaluate whether anti-HBc detection could be adopted in India as a screening assay for HBV in addition to HBsAg. METHODS: A total of 1700 serum samples collected from HBsAg-negative healthy blood donors were tested for the presence of anti-HBc antibody (IgM + IgG). All samples reactive for anti-HBc antibody were then investigated for presence of anti-HBs and for liver function tests (LFTs). One hundred serum samples reactive for anti-HBc were tested for HBV DNA by PCR method. RESULTS: Out of 1700 samples tested, 142 (8.4%) blood samples were found to be reactive for anti-HBc. It was signif icantly lower in voluntary (6.9%) as compared to replacement donors (10.4%, P = 0.011). Seventy- two (50.7%) anti-HBc reactive samples were also reactive for anti-HBs with levels > 10 mIU/mL and 70 (49.3%) samples were non-reactive for anti-HBs, these units were labeled as anti-HBc-only. These 142 anti-HBc reactive units were also tested for liver function test. HBV DNA was detected in only 1 of 100 samples tested. CONCLUSION: Keeping in view that 8%-18% of donor population in India is anti-HBc reactive, inclusion of anti- HBc testing will lead to high discard rate. Anti-HBs as proposed previously does not seem to predict clearance of the virus. Cost effectiveness of introducing universalanti-HBc screening and discarding large number of blood units versus considering ID NAT (Individual donor nuclic acid testing) needs to be assessed.展开更多
AIM: The pathogenesis of occurrence of liver inflammation and fibrosis in patients with nonalcoholic steatohepatitis (NASH) is not completely understood. Other than insulin resistance, iron abnormalities have been tho...AIM: The pathogenesis of occurrence of liver inflammation and fibrosis in patients with nonalcoholic steatohepatitis (NASH) is not completely understood. Other than insulin resistance, iron abnormalities have been thought to be one of the triggering factors. Therefore, our aim was to study the role of iron abnormalities and HFE gene mutations in patients with NASH. METHODS: Thirty-one patients of NASH diagnosed on the basis of clinical examination biochemistry, ultrasonography and liver biopsy (n = 14) were included in the study. Serum iron parameters (n = 23) (iron, ferritin, total iron-binding capacity and transferrin saturation), Perls' iron staining on liver biopsies (n = 14) and HFE gene mutations (C282Y and H63D) (n = 16) were studied in these patients. The association between iron staining, necroinflammatory activity and fibrosis stage on liver biopsies was also determined. RESULTS: Elevated serum iron, ferritin and transferrin saturation above 55% were observed in 4.3% of patients. On histology, 71% of the patients had negative iron staining, 21.4% had 1+ staining, 7.2% had 2+ staining and none had 3+ or 4+ staining. There was no association between the degree of iron staining and necroinflammatory activity (P=0.55) and fibrosis stage (P= 0.09) on histology. None of the patients had C282Y HFE gene mutation and four patients (25%) were found to be heterozygotes for H63D gene mutation. CONCLUSION: Our study does not favor iron overload and HFE gene mutations as major factors in the pathogenesis of NASH in Asian Indians.展开更多
In this paper, the authors extend [1] and provide more details of how the brain may act like a quantum computer. In particular, positing the difference between voltages on two axons as the environment for ions undergo...In this paper, the authors extend [1] and provide more details of how the brain may act like a quantum computer. In particular, positing the difference between voltages on two axons as the environment for ions undergoing spatial superposition, we argue that evolution in the presence of metric perturbations will differ from that in the absence of these waves. This differential state evolution will then encode the information being processed by the tract due to the interaction of the quantum state of the ions at the nodes with the “controlling’ potential. Upon decoherence, which is equal to a measurement, the final spatial state of the ions is decided and it also gets reset by the next impulse initiation time. Under synchronization, several tracts undergo such processes in synchrony and therefore the picture of a quantum computing circuit is complete. Under this model, based on the number of axons in the corpus callosum alone, we estimate that upwards of 50 million quantum states might be prepared and evolved every second in this white matter tract, far greater processing than any present quantum computer can accomplish.展开更多
This paper derives rigorous statements concerning the propagation velocity of action potentials in axons. The authors use the Green’s function approach to approximate the action potential and find a relation between ...This paper derives rigorous statements concerning the propagation velocity of action potentials in axons. The authors use the Green’s function approach to approximate the action potential and find a relation between conduction velocity and the impulse profile. Computer simulations are used to bolster the analysis.展开更多
With the continuous evolution and expanding applications of Large Language Models (LLMs), there has been a noticeable surge in the size of the emerging models. It is not solely the growth in model size, primarily meas...With the continuous evolution and expanding applications of Large Language Models (LLMs), there has been a noticeable surge in the size of the emerging models. It is not solely the growth in model size, primarily measured by the number of parameters, but also the subsequent escalation in computational demands, hardware and software prerequisites for training, all culminating in a substantial financial investment as well. In this paper, we present novel techniques like supervision, parallelization, and scoring functions to get better results out of chains of smaller language models, rather than relying solely on scaling up model size. Firstly, we propose an approach to quantify the performance of a Smaller Language Models (SLM) by introducing a corresponding supervisor model that incrementally corrects the encountered errors. Secondly, we propose an approach to utilize two smaller language models (in a network) performing the same task and retrieving the best relevant output from the two, ensuring peak performance for a specific task. Experimental evaluations establish the quantitative accuracy improvements on financial reasoning and arithmetic calculation tasks from utilizing techniques like supervisor models (in a network of model scenario), threshold scoring and parallel processing over a baseline study.展开更多
The recent interest in the deployment of Generative AI applications that use large language models (LLMs) has brought to the forefront significant privacy concerns, notably the leakage of Personally Identifiable Infor...The recent interest in the deployment of Generative AI applications that use large language models (LLMs) has brought to the forefront significant privacy concerns, notably the leakage of Personally Identifiable Information (PII) and other confidential or protected information that may have been memorized during training, specifically during a fine-tuning or customization process. We describe different black-box attacks from potential adversaries and study their impact on the amount and type of information that may be recovered from commonly used and deployed LLMs. Our research investigates the relationship between PII leakage, memorization, and factors such as model size, architecture, and the nature of attacks employed. The study utilizes two broad categories of attacks: PII leakage-focused attacks (auto-completion and extraction attacks) and memorization-focused attacks (various membership inference attacks). The findings from these investigations are quantified using an array of evaluative metrics, providing a detailed understanding of LLM vulnerabilities and the effectiveness of different attacks.展开更多
A new variant,JN.1,stemming from the omicron subvariant BA.2.86,garnered the attention of the World Health Organization(WHO)as a"variant of interest."Despite its rapid global spread,especially in the US,Cana...A new variant,JN.1,stemming from the omicron subvariant BA.2.86,garnered the attention of the World Health Organization(WHO)as a"variant of interest."Despite its rapid global spread,especially in the US,Canada,France,Singapore,Sweden[1],and the UK,JN.1 is considered to pose minimal danger.Current vaccinations are believed to remain effective against it.The WHO underscores the importance of maintaining immunization records amid co-occurring respiratory illnesses,and epidemiologists recommend monitoring hospitalizations,particularly in areas with low vaccination rates.展开更多
Portal hypertensive enteropathy(PHE) is a condition that describes the pathologic changes and mucosal abnormalities observed in the small intestine of patients with portal hypertension. This entity is being increasing...Portal hypertensive enteropathy(PHE) is a condition that describes the pathologic changes and mucosal abnormalities observed in the small intestine of patients with portal hypertension. This entity is being increasingly recognized and better understood over the past decade due to increased accessibility of the small intestine made possible by the introduction of video capsule endoscopy and deep enteroscopy. Though challenged by its diverse endoscopic appearance, multiple scoring systems have been proposed to classify the endoscopic presentationand grade its severity. Endoscopic findings can be broadly categorized into vascular and non-vascular lesions with many subtypes of both categories. Clinical manifestations of PHE can range from asymptomatic incidental findings to fatal gastrointestinal hemorrhage. Classic endoscopic findings in the setting of portal hypertension may lead to a prompt diagnosis. Occasionally histopathology and cross sectional imaging like computed tomography or magnetic resonance imaging may be helpful in establishing a diagnosis. Management of overt bleeding requires multidisciplinary approach involving hepatologists, endoscopists, surgeons, and interventional radiologists. Adequate resuscitation, reduction of portal pressure, and endoscopic therapeutic intervention remain the main principles of the initial treatment. This article reviews the existing evidence on PHE with emphasis on its classification, diagnosis, clinical manifestations, endoscopic appearance, pathological findings, and clinical management. A new schematic management of ectopic variceal bleed is also proposed.展开更多
Background: Endometriosis is an important cause of infertility and chronic pelvic pain. Our study aims to understand the cause and effect relationship of endometriosis with these two clinical presentations. Objectives...Background: Endometriosis is an important cause of infertility and chronic pelvic pain. Our study aims to understand the cause and effect relationship of endometriosis with these two clinical presentations. Objectives: 1) To study the correlation between stage of endometriosis with pain and infertility;2) To evaluate role of transvaginal ultrasound for diagnosis of endometriosis using laparoscopic diagnosis as gold standard. Methodology: Total of 89 women presenting with infertility and or pain and with laparoscopic findings of endometriosis were included in the study. The results were analysed by logistic regression. Results: The mean age of women was 29.67 years. Seventy three percent of patients had moderate to severe disease while 31.46% of patients with endometriosis were infertile. Symptom of pain could be categorised as dysmenorrhea (71.47%), dyspareunia (41.5%) and dyschezia (15.7%). There was no association of endometriosis stage with the pain type, duration of symptoms. Transvaginal ultrasound seems a reliable test for diagnosis of ovarian endometriosis and advanced stage disease. 87.5% of patients with ovarian endometrioma had advanced disease (higher than Stage II rAFS). Conclusion: No correlation was found between the stage of endometriosis and severity of symptoms. Presence of endometrioma on USG was associated with advanced stage of endometriosis.展开更多
AIM To evaluate the pathogenic role of toll-like receptor(TLR) gene polymorphisms in patients with nonalcoholic fatty liver disease(NAFLD).METHODS Two hundred and fifty subjects(NAFLD = 200, healthy volunteers = 50) u...AIM To evaluate the pathogenic role of toll-like receptor(TLR) gene polymorphisms in patients with nonalcoholic fatty liver disease(NAFLD).METHODS Two hundred and fifty subjects(NAFLD = 200, healthy volunteers = 50) underwent polymerase chain reaction and restriction fragment length polymorphism to assess one polymorphism in the toll-like receptor 2(TLR2) gene(A753G), two polymorphisms in the TLR4 gene(TLR4 Asp299 Gly and Thr399 Ile allele), and two polymorphisms in the cluster of differentiation 14(CD14)(C-159 T and C-550T) gene, a co-receptor of TLR4. Association of TLR gene polymorphisms with NAFLD and its severity was evaluated by genetic models of association.RESULTS On both multiplicative and recessive models of gene polymorphism association, there was significant association of CD14 C(-159) T polymorphism with NAFLD; patients with TT genotype had a 2.6 fold increased risk of developing NAFLD in comparison to CC genotype. There was no association of TLR2 Arg753 Gln, TLR4 Asp299 Gly, Thr399 Ile, and CD14 C(-550) T polymorphisms with NAFLD. None of the TLR gene polymorphisms had an association with histological severity of NAFLD.CONCLUSION Patients with CD14 C(-159) T gene polymorphism, a co-receptor of TLR4, have an increased risk of NAFLD development.展开更多
In this paper, the authors investigate compound action potentials formed when the underlying tract's axons have current-mediated coupling amongst themselves, and no field-mediated coupling. The key finding of the ...In this paper, the authors investigate compound action potentials formed when the underlying tract's axons have current-mediated coupling amongst themselves, and no field-mediated coupling. The key finding of the paper is that, for the case of biophysically inhomogeneous axon tracts, the compound action potential is governed by a Hodgkin-Huxley like equation itself in certain cases. The paper extends an earlier result for the identical axon case.展开更多
The article titled“Accessibility and Utilization of Healthcare Services Among Diabetic Patients:Is Diabetes a Poor Man’s Ailment?”gave insights into a pandemic systemic disease known as diabetes mellitus.This moder...The article titled“Accessibility and Utilization of Healthcare Services Among Diabetic Patients:Is Diabetes a Poor Man’s Ailment?”gave insights into a pandemic systemic disease known as diabetes mellitus.This modern-era pandemic affects everyone,regardless of their financial background.As a result,diabetes is not a systemic disease which just involves people of low socioeconomic status.展开更多
BACKGROUND Hepatosplenic T-cell lymphoma(HSTCL)is a rare and aggressive peripheral T-cell lymphoma with historically dismal outcomes,representing less than one percent of non-Hodgkin lymphomas.Given its rarity,the tru...BACKGROUND Hepatosplenic T-cell lymphoma(HSTCL)is a rare and aggressive peripheral T-cell lymphoma with historically dismal outcomes,representing less than one percent of non-Hodgkin lymphomas.Given its rarity,the true incidence of HSTCL is unknown and most data have been extrapolated through case reports.To the best of our knowledge,the largest and most up to date study addressing the epidemiology and outcomes of patients with HSTCL in the United States covered a period from 1996 to 2014,with a sample size of 122 patients.AIM To paint the most updated epidemiological picture of HSTCL.METHODS A total of 186 patients diagnosed with HSTCL,between 2000 and 2017,were ultimately enrolled in our study by retrieving data from the Surveillance,Epidemiology,and End Results database.We analyzed demographics,clinical characteristics,and overall mortality(OM)as well as cancer-specific mortality(CSM)of HSTCL.Variables with a P value<0.01 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors,with a hazard ratio of greater than 1 representing adverse prog-nostic factors.CONCLUSION Overall,the outlook for this rare malignancy is very grim.In this retrospective cohort study of the United States population,non-Hispanic blacks and the elderly had a higher CSM.This data highlights the need for larger prospective studies to investigate factors associated with worse prognosis in one ethnic group,such as treatment delays,which have been shown to increase mortality in this racial/ethnic group for other cancers.展开更多
文摘Diabetic nephropathy has been the cause of lot of morbidity and mortality in the diabetic population. The renin angiotensin system (RAS) is considered to be involved in most of the pathological processes that result in diabetic nephropathy. This system has various subsystems which contribute to the disease pathology. One of these involves angiotensin II (Ang II) which shows increased activity during diabetic nephropathy. This causes hypertrophy of various renal cells and has a pressor effect on arteriolar smooth muscle resulting in increased vascular pressure. Ang II also induces inflammation, apoptosis, cell growth, migration and differentiation. Monocyte chemoattractant protein-1 production responsible for renal fibrosis is also regulated by RAS. Polymorphism of angiotensin converting enzyme (ACE) and Angiotensinogen has been shown to have effects on RAS. Available treatment modalities have proven effective in controlling the progression of nephropathy. Various drugs (based on antagonism of RAS) are currently in the market and others are still under trial. Amongst the approved drugs, ACE inhibitors and angiotensin receptor blockers (ARBs) are widely used in clinical practice. ARBs are shown to be superior to ACE inhibitors in terms of reducing proteinuria but the combined role of ARBs with ACE inhibitors in diabetic nephropathy is under debate.
文摘AIM: To compare the utility of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) and Asia-Pacific Association for the Study of Liver (APASL) definitions of acute-on-chronic liver failure (ACLF) in predicting short-term prognosis of patients with ACLF.
文摘AIM: To systematically review evidence on pathophysiology of intra-abdominal pressure(IAP) in acute pancreatitis(AP) with its clinical correlates. METHODS: Systematic review of available evidence in English literature with relevant medical subject heading terms on Pub Med, Medline and Scopus with further search from open access sources on internet as suggested by articles retrieved. RESULTS: Intra-abdominal hypertension(IAH) is increasingly gaining recognition as a point of specific intervention with potential to alter disease outcome and improve mortality in AP. IAH can be expected in at least 17% of patients presenting with diagnosis of AP to a typical tertiary care hospital(prevalence increasing to 50% in those with severe disease). Abdominal compartment syndrome can be expected in at least 15% patients with severe disease. Recent guidelines on management of AP do not acknowledge utility of surveillance for IAP other than those by Japanese Society of Hepato-BiliaryPancreatic Surgery. We further outline pathophysiologic mechanisms of IAH; understanding of which advances our knowledge and helps to coherently align common observed variations in management related conundrums(such as fluid therapy, nutrition and antibiotic prophylaxis) with potential to further individualize treatment in AP. CONCLUSION: We suggest that IAP be given its due place in future practice guidelines and that recommendations be formed with help of a broader panel with inclusion of clinicians experienced in management of IAH.
文摘Hepatocellular carcinoma(HCC) is primarily a malignancy of the liver, advancing from a damaged, cirrhotic liver to HCC. Globally, HCC is the sixth most prevalent cancer and the third-most prevalent reason for neoplastic disease-related deaths. A diverse array of infiltrating immunocytes regulates the development and progression of HCC, as is the case in many other cancers. An understanding of the various immune components during HCC becomes necessary so that novel therapeutic strategies can be designed to combat the disease. A dysregulated immune system(including changes in the number and/or function of immune cells, cytokine levels, and the expression of inhibitory receptors or their ligands) plays a key role in the development of HCC. Alterations in either the innate or adaptive arm of the immune system and cross-talk between them make the immune system tolerant to tumors, leading to disease progression. In this review, we have discussed the status and roles of various immune effector cells(e.g., dendritic cells, natural killer cells, macrophages, and T cells), their cytokine profile, and the chemokine-receptor axis in promoting or impeding HCC.
文摘Hepatitis E viral infection has traditionally been considered an acute, self-limited, water borne disease similar to hepatitis A, endemic to developing countries. However, over the past decade, zoonotic transmission and progression to chronicity in human patients has been identified, resulting in persistently elevated transaminase levels, progressive liver injury and cirrhosis. In addition to liver injury, neurological, renal and rheumatological manifestations have also been reported. Chronic hepatitis E occurs mainly in immunosuppressed individuals such as transplant recipients, human immunodeficiency virus patients with low CD4 counts and in patients with hematological malignancies receiving chemotherapy. Diagnosis is established by persistent elevation of hepatitis E virus RNA in the stool or serum. This population often requires treatment with antiviral agents, particularly ribavirin, as spontaneous clearance with reduction in immunosuppression occurs only in about a third of the patients. The purpose of this review, is to further discuss the clinical presentation, and recent advances in diagnosis, treatment and prophylaxis of chronic hepatitis E.
文摘The present study highlights the rich species diversity of higher plants in the Bhabha Valley of western Himalaya in India. The analysis of species diversity revealed that a total of 313 species of higher plants inhabit the valley with a characteristic of moist alpine shrub vegetation. The herbaceous life forms dominate and increase with increasing altitude. The major representations are from the families Asteraceae, Rosaceae, Lamiaceae and Poaceae, suggesting thereby the alpine meadow nature of the study area. The effect of altitude on species diversity displays a hump-shaped curve which may be attributed to increase in habitat diversity at the median ranges and relatively less habitat diversity at higher altitudes. The anthropogenic pressure at lower altitudes results in low plant diversity towards the bottom of the valley with most of the species being exotic in nature. Though the plant diversity is less at higher altitudinal ranges, the uniqueness is relatively high with high species replacement rates. More than 90 % of variability in the species diversity could be explained using appropriate quantitative and statistical analysis along the altitudinal gradient. The valley harbours 18 threatened and 41 endemic species, most of which occur at higher altitudinal gradients due to habitat specificity.
文摘AIM:To study the seroprevalence of antibody to hepatitis B core antigen (anti-HBc) in healthy blood donors negative for HBsAg and to evaluate whether anti-HBc detection could be adopted in India as a screening assay for HBV in addition to HBsAg. METHODS: A total of 1700 serum samples collected from HBsAg-negative healthy blood donors were tested for the presence of anti-HBc antibody (IgM + IgG). All samples reactive for anti-HBc antibody were then investigated for presence of anti-HBs and for liver function tests (LFTs). One hundred serum samples reactive for anti-HBc were tested for HBV DNA by PCR method. RESULTS: Out of 1700 samples tested, 142 (8.4%) blood samples were found to be reactive for anti-HBc. It was signif icantly lower in voluntary (6.9%) as compared to replacement donors (10.4%, P = 0.011). Seventy- two (50.7%) anti-HBc reactive samples were also reactive for anti-HBs with levels > 10 mIU/mL and 70 (49.3%) samples were non-reactive for anti-HBs, these units were labeled as anti-HBc-only. These 142 anti-HBc reactive units were also tested for liver function test. HBV DNA was detected in only 1 of 100 samples tested. CONCLUSION: Keeping in view that 8%-18% of donor population in India is anti-HBc reactive, inclusion of anti- HBc testing will lead to high discard rate. Anti-HBs as proposed previously does not seem to predict clearance of the virus. Cost effectiveness of introducing universalanti-HBc screening and discarding large number of blood units versus considering ID NAT (Individual donor nuclic acid testing) needs to be assessed.
文摘AIM: The pathogenesis of occurrence of liver inflammation and fibrosis in patients with nonalcoholic steatohepatitis (NASH) is not completely understood. Other than insulin resistance, iron abnormalities have been thought to be one of the triggering factors. Therefore, our aim was to study the role of iron abnormalities and HFE gene mutations in patients with NASH. METHODS: Thirty-one patients of NASH diagnosed on the basis of clinical examination biochemistry, ultrasonography and liver biopsy (n = 14) were included in the study. Serum iron parameters (n = 23) (iron, ferritin, total iron-binding capacity and transferrin saturation), Perls' iron staining on liver biopsies (n = 14) and HFE gene mutations (C282Y and H63D) (n = 16) were studied in these patients. The association between iron staining, necroinflammatory activity and fibrosis stage on liver biopsies was also determined. RESULTS: Elevated serum iron, ferritin and transferrin saturation above 55% were observed in 4.3% of patients. On histology, 71% of the patients had negative iron staining, 21.4% had 1+ staining, 7.2% had 2+ staining and none had 3+ or 4+ staining. There was no association between the degree of iron staining and necroinflammatory activity (P=0.55) and fibrosis stage (P= 0.09) on histology. None of the patients had C282Y HFE gene mutation and four patients (25%) were found to be heterozygotes for H63D gene mutation. CONCLUSION: Our study does not favor iron overload and HFE gene mutations as major factors in the pathogenesis of NASH in Asian Indians.
文摘In this paper, the authors extend [1] and provide more details of how the brain may act like a quantum computer. In particular, positing the difference between voltages on two axons as the environment for ions undergoing spatial superposition, we argue that evolution in the presence of metric perturbations will differ from that in the absence of these waves. This differential state evolution will then encode the information being processed by the tract due to the interaction of the quantum state of the ions at the nodes with the “controlling’ potential. Upon decoherence, which is equal to a measurement, the final spatial state of the ions is decided and it also gets reset by the next impulse initiation time. Under synchronization, several tracts undergo such processes in synchrony and therefore the picture of a quantum computing circuit is complete. Under this model, based on the number of axons in the corpus callosum alone, we estimate that upwards of 50 million quantum states might be prepared and evolved every second in this white matter tract, far greater processing than any present quantum computer can accomplish.
文摘This paper derives rigorous statements concerning the propagation velocity of action potentials in axons. The authors use the Green’s function approach to approximate the action potential and find a relation between conduction velocity and the impulse profile. Computer simulations are used to bolster the analysis.
文摘With the continuous evolution and expanding applications of Large Language Models (LLMs), there has been a noticeable surge in the size of the emerging models. It is not solely the growth in model size, primarily measured by the number of parameters, but also the subsequent escalation in computational demands, hardware and software prerequisites for training, all culminating in a substantial financial investment as well. In this paper, we present novel techniques like supervision, parallelization, and scoring functions to get better results out of chains of smaller language models, rather than relying solely on scaling up model size. Firstly, we propose an approach to quantify the performance of a Smaller Language Models (SLM) by introducing a corresponding supervisor model that incrementally corrects the encountered errors. Secondly, we propose an approach to utilize two smaller language models (in a network) performing the same task and retrieving the best relevant output from the two, ensuring peak performance for a specific task. Experimental evaluations establish the quantitative accuracy improvements on financial reasoning and arithmetic calculation tasks from utilizing techniques like supervisor models (in a network of model scenario), threshold scoring and parallel processing over a baseline study.
文摘The recent interest in the deployment of Generative AI applications that use large language models (LLMs) has brought to the forefront significant privacy concerns, notably the leakage of Personally Identifiable Information (PII) and other confidential or protected information that may have been memorized during training, specifically during a fine-tuning or customization process. We describe different black-box attacks from potential adversaries and study their impact on the amount and type of information that may be recovered from commonly used and deployed LLMs. Our research investigates the relationship between PII leakage, memorization, and factors such as model size, architecture, and the nature of attacks employed. The study utilizes two broad categories of attacks: PII leakage-focused attacks (auto-completion and extraction attacks) and memorization-focused attacks (various membership inference attacks). The findings from these investigations are quantified using an array of evaluative metrics, providing a detailed understanding of LLM vulnerabilities and the effectiveness of different attacks.
文摘A new variant,JN.1,stemming from the omicron subvariant BA.2.86,garnered the attention of the World Health Organization(WHO)as a"variant of interest."Despite its rapid global spread,especially in the US,Canada,France,Singapore,Sweden[1],and the UK,JN.1 is considered to pose minimal danger.Current vaccinations are believed to remain effective against it.The WHO underscores the importance of maintaining immunization records amid co-occurring respiratory illnesses,and epidemiologists recommend monitoring hospitalizations,particularly in areas with low vaccination rates.
文摘Portal hypertensive enteropathy(PHE) is a condition that describes the pathologic changes and mucosal abnormalities observed in the small intestine of patients with portal hypertension. This entity is being increasingly recognized and better understood over the past decade due to increased accessibility of the small intestine made possible by the introduction of video capsule endoscopy and deep enteroscopy. Though challenged by its diverse endoscopic appearance, multiple scoring systems have been proposed to classify the endoscopic presentationand grade its severity. Endoscopic findings can be broadly categorized into vascular and non-vascular lesions with many subtypes of both categories. Clinical manifestations of PHE can range from asymptomatic incidental findings to fatal gastrointestinal hemorrhage. Classic endoscopic findings in the setting of portal hypertension may lead to a prompt diagnosis. Occasionally histopathology and cross sectional imaging like computed tomography or magnetic resonance imaging may be helpful in establishing a diagnosis. Management of overt bleeding requires multidisciplinary approach involving hepatologists, endoscopists, surgeons, and interventional radiologists. Adequate resuscitation, reduction of portal pressure, and endoscopic therapeutic intervention remain the main principles of the initial treatment. This article reviews the existing evidence on PHE with emphasis on its classification, diagnosis, clinical manifestations, endoscopic appearance, pathological findings, and clinical management. A new schematic management of ectopic variceal bleed is also proposed.
文摘Background: Endometriosis is an important cause of infertility and chronic pelvic pain. Our study aims to understand the cause and effect relationship of endometriosis with these two clinical presentations. Objectives: 1) To study the correlation between stage of endometriosis with pain and infertility;2) To evaluate role of transvaginal ultrasound for diagnosis of endometriosis using laparoscopic diagnosis as gold standard. Methodology: Total of 89 women presenting with infertility and or pain and with laparoscopic findings of endometriosis were included in the study. The results were analysed by logistic regression. Results: The mean age of women was 29.67 years. Seventy three percent of patients had moderate to severe disease while 31.46% of patients with endometriosis were infertile. Symptom of pain could be categorised as dysmenorrhea (71.47%), dyspareunia (41.5%) and dyschezia (15.7%). There was no association of endometriosis stage with the pain type, duration of symptoms. Transvaginal ultrasound seems a reliable test for diagnosis of ovarian endometriosis and advanced stage disease. 87.5% of patients with ovarian endometrioma had advanced disease (higher than Stage II rAFS). Conclusion: No correlation was found between the stage of endometriosis and severity of symptoms. Presence of endometrioma on USG was associated with advanced stage of endometriosis.
基金Supported by Indian Council of Medical Research(ICMR),New Delhi,No.5/4/3-7/2009-NCD-II
文摘AIM To evaluate the pathogenic role of toll-like receptor(TLR) gene polymorphisms in patients with nonalcoholic fatty liver disease(NAFLD).METHODS Two hundred and fifty subjects(NAFLD = 200, healthy volunteers = 50) underwent polymerase chain reaction and restriction fragment length polymorphism to assess one polymorphism in the toll-like receptor 2(TLR2) gene(A753G), two polymorphisms in the TLR4 gene(TLR4 Asp299 Gly and Thr399 Ile allele), and two polymorphisms in the cluster of differentiation 14(CD14)(C-159 T and C-550T) gene, a co-receptor of TLR4. Association of TLR gene polymorphisms with NAFLD and its severity was evaluated by genetic models of association.RESULTS On both multiplicative and recessive models of gene polymorphism association, there was significant association of CD14 C(-159) T polymorphism with NAFLD; patients with TT genotype had a 2.6 fold increased risk of developing NAFLD in comparison to CC genotype. There was no association of TLR2 Arg753 Gln, TLR4 Asp299 Gly, Thr399 Ile, and CD14 C(-550) T polymorphisms with NAFLD. None of the TLR gene polymorphisms had an association with histological severity of NAFLD.CONCLUSION Patients with CD14 C(-159) T gene polymorphism, a co-receptor of TLR4, have an increased risk of NAFLD development.
文摘In this paper, the authors investigate compound action potentials formed when the underlying tract's axons have current-mediated coupling amongst themselves, and no field-mediated coupling. The key finding of the paper is that, for the case of biophysically inhomogeneous axon tracts, the compound action potential is governed by a Hodgkin-Huxley like equation itself in certain cases. The paper extends an earlier result for the identical axon case.
文摘The article titled“Accessibility and Utilization of Healthcare Services Among Diabetic Patients:Is Diabetes a Poor Man’s Ailment?”gave insights into a pandemic systemic disease known as diabetes mellitus.This modern-era pandemic affects everyone,regardless of their financial background.As a result,diabetes is not a systemic disease which just involves people of low socioeconomic status.
文摘BACKGROUND Hepatosplenic T-cell lymphoma(HSTCL)is a rare and aggressive peripheral T-cell lymphoma with historically dismal outcomes,representing less than one percent of non-Hodgkin lymphomas.Given its rarity,the true incidence of HSTCL is unknown and most data have been extrapolated through case reports.To the best of our knowledge,the largest and most up to date study addressing the epidemiology and outcomes of patients with HSTCL in the United States covered a period from 1996 to 2014,with a sample size of 122 patients.AIM To paint the most updated epidemiological picture of HSTCL.METHODS A total of 186 patients diagnosed with HSTCL,between 2000 and 2017,were ultimately enrolled in our study by retrieving data from the Surveillance,Epidemiology,and End Results database.We analyzed demographics,clinical characteristics,and overall mortality(OM)as well as cancer-specific mortality(CSM)of HSTCL.Variables with a P value<0.01 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors,with a hazard ratio of greater than 1 representing adverse prog-nostic factors.CONCLUSION Overall,the outlook for this rare malignancy is very grim.In this retrospective cohort study of the United States population,non-Hispanic blacks and the elderly had a higher CSM.This data highlights the need for larger prospective studies to investigate factors associated with worse prognosis in one ethnic group,such as treatment delays,which have been shown to increase mortality in this racial/ethnic group for other cancers.
