VER-Net: a hybrid transfer learning model for lung cancer detection using CT scan images.

BACKGROUND: Lung cancer is the second most common cancer worldwide, with over two million new cases per year. Early identification would allow healthcare practitioners to handle it more effectively. The advancement of computer-aided detection systems significantly impacted clinical analysis and decision-making on human disease. Towards this, machine learning and deep learning techniques are successfully being applied. Due to several advantages, transfer learning has become popular for disease detection based on image data. METHODS: In this work, we build a novel transfer learning model (VER-Net) by stacking three different transfer learning models to detect lung cancer using lung CT scan images. The model is trained to map the CT scan images with four lung cancer classes. Various measures, such as image preprocessing, data augmentation, and hyperparameter tuning, are taken to improve the efficacy of VER-Net. All the models are trained and evaluated using multiclass classifications chest CT images. RESULTS: The experimental results confirm that VER-Net outperformed the other eight transfer learning models compared with. VER-Net scored 91%, 92%, 91%, and 91.3% when tested for accuracy, precision, recall, and F1-score, respectively. Compared to the state-of-the-art, VER-Net has better accuracy. CONCLUSION: VER-Net is not only effectively used for lung cancer detection but may also be useful for other diseases for which CT scan images are available.

Microbiome interactions with different risk factors in development of myocardial infarction.

Among all non-communicable diseases, Cardiovascular Diseases (CVDs) stand as the leading global cause of mortality. Within this spectrum, Myocardial Infarction (MI) strikingly accounts for over 15 % of all deaths. The intricate web of risk factors for MI, comprising family history, tobacco use, oral health, hypertension, nutritional pattern, and microbial infections, is firmly influenced by the human gut and oral microbiota, their diversity, richness, and dysbiosis, along with their respective metabolites. Host genetic factors, especially allelic variations in signaling and inflammatory markers, greatly affect the progression or severity of the disease. Despite the established significance of the human microbiome-nutrient-metabolite interplay in associations with CVDs, the unexplored terrain of the gut-heart-oral axis has risen as a critical knowledge gap. Moreover, the pivotal role of the microbiome and the complex interplay with host genetics, compounded by age-related changes, emerges as an area of vital importance in the development of MI. In addition, a distinctive disease susceptibility and severity influenced by gender-based or ancestral differences, adds a crucial insights to the association with increased mortality. Here, we aimed to provide an overview on interactions of microbiome (oral and gut) with major risk factors (tobacco use, alcohol consumption, diet, hypertension host genetics, gender, and aging) in the development of MI and therapeutic regulation.

Unveiling HPV's hidden link: Cardiovascular diseases and the viral intrigue.

Cardiovascular diseases (CVD) remain a major global health challenge, with an escalating impact on mortality despite advancements in managing conventional risk factors. This review investigates the intricate relationship between human papillomavirus (HPV) and CVD, shedding light on a novel aspect of cardiovascular health. Despite significant progress in understanding and managing traditional CVD risk factors, a substantial proportion of CVD cases lack these conventional markers. Recent research has unveiled HPV, a prevalent sexually transmitted infection, as a potential unconventional risk factor for CVD. This review delves into the underlying mechanisms linking HPV to CVD pathogenesis. HPV's influence on vascular endothelium and induction of systemic inflammation are key contributors. Additionally, HPV disrupts host lipid metabolism, further exacerbating the development of atherosclerosis. The link between HPV and CAD is not merely correlative; it encompasses a complex interplay of virological, immunological, and metabolic factors. Understanding the connection between HPV and CVD holds transformative potential. Insights from this review not only underscore the significance of considering HPV as a crucial risk factor but also advocate for targeted HPV screening and vaccination strategies to mitigate CVD risks. This multidisciplinary exploration bridges the gap between infectious diseases and cardiovascular health, emphasizing the need for a comprehensive approach to combating the global burden of cardiovascular disease. Further research and clinical guidelines in this realm are essential to harness the full scope of preventive and therapeutic interventions, ultimately shaping a healthier cardiovascular landscape.

Medicinal Effects, Phytochemistry, Pharmacology of Euphorbia prostrata and Promising Molecular Mechanisms.

Euphorbiaceae is a large family of dicotyledonous angiosperms with diverse genera including Euphorbia prostrata (E. prostrata). Current research has provided scientific evidence for traditional uses of E. prostrata against diverse pathological conditions such as anti-hemorrhoidal, anti-inflammatory, analgesic, wound healing, antioxidant, antibacterial, leishmanicidal, antitumor activity, and so on. The phytochemical screening has revealed the presence of glycosides, phytosterols, flavonoids, polyphenols, tannins, and anthraquinones with chemical structures elucidation of their respective compounds. The uniqueness of such multifactorial compounds present in this species endorses it as the potent therapeutic or prophylactic choice for several fatal diseases. Although ethnomedical applications served as a significant citation for pharmacology, the molecular mechanism has not been reviewed yet. The present paper provides a comprehensive review of research outcomes, pharmacology, toxicology, and molecular signaling of phytochemicals of E. prostrata species as a reference for relevant researchers. The study of bioactive compounds in crude extracts and fractions, the demonstration of primary mechanisms of pharmacology, along with the addition of toxicity, and clinical trials, should be conceded in depth. This review underlines the E. prostrata species that can be a promising phytomedicine since we are committed to excavating more intensely into their pharmacological role.

Position statement from the Indian Society of Gastroenterology, Cardiological Society of India, Indian Academy of Neurology and Vascular Society of India on gastrointestinal bleeding and endoscopic procedures in patients on antiplatelet and/or anticoagulant therapy.

Antiplatelet and/or anticoagulant agents (collectively known as antithrombotic agents) are used to reduce the risk of thromboembolic events in patients with conditions such as atrial fibrillation, acute coronary syndrome, recurrent stroke prevention, deep vein thrombosis, hypercoagulable states and endoprostheses. Antithrombotic-associated gastrointestinal (GI) bleeding is an increasing burden due to the growing population of advanced age with multiple comorbidities and the expanding indications for the use of antiplatelet agents and anticoagulants. GI bleeding in antithrombotic users is associated with an increase in short-term and long-term mortality. In addition, in recent decades, there has been an exponential increase in the use of diagnostic and therapeutic GI endoscopic procedures. Since endoscopic procedures hold an inherent risk of bleeding that depends on the type of endoscopy and patients' comorbidities, in patients already on antithrombotic therapies, the risk of procedure-related bleeding is further increased. Interrupting or modifying doses of these agents prior to any invasive procedures put these patients at increased risk of thromboembolic events. Although many international GI societies have published guidelines for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures, no Indian guidelines exist that cater to Indian gastroenterologists and their patients. In this regard, the Indian Society of Gastroenterology (ISG), in association with the Cardiological Society of India (CSI), Indian Academy of Neurology (IAN) and Vascular Society of India (VSI), have developed a "Guidance Document" for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures.

Evaluation of immunodominant peptides of in vivo expressed mycobacterial antigens in an ELISA-based diagnostic assay for pulmonary tuberculosis.

Non-sputum-based biomarker assay is urgently required as per WHO's target product pipeline for diagnosis of tuberculosis. Therefore, the current study was designed to evaluate the utility of previously identified proteins, encoded by in vivo expressed mycobacterial transcripts in pulmonary tuberculosis, as diagnostic targets for a serodiagnostic assay. A total of 300 subjects were recruited including smear+, smear- pulmonary tuberculosis (PTB) patients, sarcoidosis patients, lung cancer patients and healthy controls. Proteins encoded by eight in vivo expressed transcripts selected from previous study including those encoded by two topmost expressed and six RD transcripts (Rv0986, Rv0971, Rv1965, Rv1971, Rv2351c, Rv2657c, Rv2674, Rv3121) were analyzed for B-cell epitopes by peptide arrays/bioinformatics. Enzyme-linked immunosorbent assay was used to evaluate the antibody response against the selected peptides in sera from PTB and controls. Overall 12 peptides were selected for serodiagnosis. All the peptides were initially screened for their antibody response. The peptide with highest sensitivity and specificity was further assessed for its serodiagnostic ability in all the study subjects. The mean absorbance values for antibody response to selected peptide were significantly higher (p<0.001) in PTB patients as compared to healthy controls; however, the sensitivity for diagnosis of PTB was 31% for smear+ and 20% for smear- PTB patients. Thus, the peptides encoded by in vivo expressed transcripts elicited a significant antibody response, but are not suitable candidates for serodiagnosis of PTB.

Cerebrospinal fluid adenosine deaminase for the diagnosis of tuberculous meningitis.

Background: A consensus on the diagnostic utility of cerebrospinal fluid adenosine deaminase (ADA) for tuberculous meningitis (TBM) is lacking. Methods: Patients aged ≥12 years admitted with CNS infections were enrolled prospectively. ADA was measured with spectrophotometry. Results: We enrolled 251 TBM and 131 other CNS infections. The optimal cutoff of ADA was calculated at 5.5 U/l against microbiological reference standard with area under curve 0.743, sensitivity 80.7%, specificity 60.3%, positive likelihood ratio 2.03 and negative likelihood ratio 3.12. The widely used cutoff value 10 U/l had specificity 82% and sensitivity 50%. The discriminating power was higher for TBM versus viral meningoencephalitis than bacterial or cryptococcal meningitis. Conclusion: Cerebrospinal fluid ADA has a low-to-modest diagnostic utility.

The diagnosis of tuberculosis (TB) of the brain is mainly made by testing cerebrospinal fluid, a clear liquid that flows in and around the brain and spinal cord. Adenosine deaminase (ADA) is a protein whose production and activity are increased in many diseases, such as TB. ADA testing in cerebrospinal fluid is widely used for the diagnosis of brain TB. However, the experts have split opinions regarding its confirmatory role. This study explores ADA measurement in cerebrospinal fluid for differentiating TB from other brain infections. The report says that this simple and inexpensive test can be helpful, but it cannot make or refute the diagnosis of brain TB and should only be considered along with other tests.

Non-compliance to the Tobacco Control and Regulatory Act among Vendors in the Vicinities of Schools of a Metropolitan City: A Descriptive Cross-sectional Study.

Introduction: Tobacco use is the underlying cause of ill health, preventable deaths, and disabilities worldwide. The Tobacco Product Control and Regulation Act 2011 prohibits the sale of tobacco in public places including educational institutions but non-compliance to the law had not been assessed. This study aimed to find out the prevalence of non-compliance to the Tobacco Product Control and Regulation Act among vendors in the vicinities of schools in a metropolitan city. Methods: This descriptive cross-sectional study was conducted in a metropolitan city in August 2018. Ethical approval was taken from Institutional Review Committee [Reference number: 23(6-11-E)2/075/076]. A convenience sampling method was used to recruit vendors within 100 meters radius of secondary schools. The data were collected through face-to-face interviews using a semi-structured questionnaire. Point estimate and 95% Confidence Interval were calculated. Results: Out of total 217 vendors, non-compliance to the section 3 of section 11 of Tobacco Product Control and Regulation Act was found in 195 (89.86%) (85.84-93.88 at 95% Confidence Interval). Among the non-compliers, 110 (56.41%) were selling both smoked and smokeless tobacco products, 78 (40%) were selling smoked and 7 (3.59%) were selling smokeless tobacco products. Conclusions: The non-compliance with Tobacco Product Control and Regulation Act's prohibition of tobacco sales within 100 m of schools in Kathmandu Metropolitan was similar with other studies conducted in similar settings. Keywords: government regulations; primary schools; vendors.

Clinical spectrum and outcomes of geriatric tuberculosis emergencies in North India.

OBJECTIVES: Despite the acute and life-threatening repercussions that tuberculosis (TB) may have on the burgeoning older population in endemic countries like India, the spectrum of geriatric TB emergencies is not adequately understood. METHODS: We performed a prospective observational study at the emergency department of an academic hospital in north India between January 2019 and June 2020, investigating the clinical and laboratory features and outcomes of active TB in older patients aged 60 years and above. RESULTS: Out of 71 geriatric TB emergencies, central nervous system disease predominated (n = 41, 57.7%), followed by pulmonary (n = 16, 22.5%), pleural TB (n = 8, 11.3%), and multisite involvement (n = 6, 8.4%). Nearly 71.8% were male, and 77.4% belonged to low socioeconomic status (lower-middle or lower class). Usual predisposing factors were tobacco smoking (38.0%), chronic alcohol use (27.0%), and diabetes mellitus (23.9%). Atypical features were more frequent with extrapulmonary TB. Only 28.2% were microbiologically confirmed cases, and rifampicin resistance was seen in only one case. The mortality rate was considerably high (24.0%), highest with pulmonary TB (37.0%). CONCLUSION: Older patients with TB emergencies have atypical presentations, diagnostic difficulties, and high mortality.

Diagnostic Utility of Biplex/Multiplex Polymerase Chain Reaction in Infectious Granulomatous Dermatitis in North Indian Population.

BACKGROUND: A definite diagnosis of infectious granulomatous dermatitis (IGD) is difficult for both practicing dermatologists and dermatopathologists due to overlapping clinical and histomorphological features. We aimed to explore the role of multiplex polymerase chain reaction (PCR) for identifying a definite etiological agent for diagnosis and appropriate treatment in IGD in formalin-fixed paraffin-embedded tissue. MATERIALS AND METHODS: Sixty-two cases of IGD were included, excluding leprosy. The histochemical stains including Ziehl-Neelsen, periodic acid-Schiff, and Giemsa were performed in all cases. A multiplex PCR was designed for detection of tuberculosis (TB) (IS6110 and mpt64), fungal infections (ITS1, ITS2; ZM1, and ZM3), and leishmaniasis (kDNA). The results of histomorphology, histochemical stains, and multiplex PCR were compared. RESULTS: Among 62 cases, the sensitivity rate of PCR detection for organisms was 16.7%, 0%, 100%, 72%, 75%, and 66.7% in patients with TB, suggestive of TB, leishmaniasis, fungal infections, and granulomatous dermatitis not otherwise specified and granulomatous dermatitis suggestive of fungus, respectively. The TB PCR using IS6110 primers was negative in all cases; however, PCR using mpt64 primers was positive in 33.33% cases of scrofuloderma. The histochemical stains including Ziehl-Neelsen for acid-fast bacilli, periodic acid-Schiff for fungus, and Giemsa for Leishman-Donovan bodies showed positivity in 11.3%, 43.5%, and 3.2%, respectively. CONCLUSION: A multiplex PCR (Mycobacterium tuberculosis, Leishmania, and panfungal) is highly recommended in all cases of IGD where an etiological agent is difficult to establish by skin biopsy and histochemical stains along with a clinicopathological correlation. This will augment in appropriate treatment and will reduce empirical treatment and morbidity in such patients.

Bronchospasmolytic and Adenosine Binding Activity of 8- (Proline / Pyrazole)- Substituted Xanthine Derivatives.

BACKGROUND: 8-Phenyltheophylline derivatives exhibit prophylactic effects at a specific dose but do not produce the cardiovascular or emetic side effects associated with xanthines, thereby exhibiting unique characteristics of potential therapeutic importance. METHODS: Novel series of 8-(proline/pyrazole)-substituted xanthine analogs have been synthesized. The affinity and selectivity of compounds to adenosine receptors have been assessed by radioligand binding studies. The synthesized compounds also showed good bronchospasmolytic properties (increased onset of bronchospasm; decreased duration of jerks) with 100% survival of animals in comparison to the standard drug. Besides, compound 8f & 9f showed good binding affinity in comparison to other synthesized compounds in the micromolar range. RESULTS: The maximum binding affinity of these compounds was observed for A2B receptors, which was ~ 7 or 10 times higher as compared to A1, A2A and A3 receptors. The newly synthesized derivatives 8f, 9a-f, 17g-m, and 18g-m displayed significant protection against histamine aerosol induced bronchospasm in guinea pigs. CONCLUSION: Newly synthesized proline/pyrazole based xanthines compounds showed a satisfactory binding affinity for adenosine receptor subtypes. Replacement or variation of substituted proline ring with substituted pyrazole scaffold at the 8th-position of xanthine moiety resulted in the reduction of adenosine binding affinity and bronchospasmolytic effects.

1,8-Naphthyridine Derivatives: A Privileged Scaffold for Versatile Biological Activities.

1, 8- Naphthyridine nucleus belongs to significant nitrogen-containing heterocyclic compounds which has garnered the interest of researchers due to its versatile biological activities. It is known to be used as an antimicrobial, anti-psychotic, anti-depressant, anti-convulsant, anti- Alzheimer's, anti-cancer, analgesic, anti-inflammatory, antioxidant, anti-viral, anti-hypertensive, antimalarial, pesticides, anti-platelets, and CB2 receptor agonist, etc. The present review highlights the framework of biological properties of synthesized 1, 8-naphthyridine derivatives developed by various research groups across the globe.

Bronchospasmolytic activity and adenosine receptor binding of some newer 1,3-dipropyl-8-phenyl substituted xanthine derivatives.

The aldehyde derivatives of 1,3-dipropyl xanthines as described in this paper, constitutes a new series of selective adenosine ligands displaying bronchospasmolytic activity. The effect of substitution at third- and fourth-position of 8-phenyl xanthine has also been taken into consideration. The synthesized compounds showed varying binding affinities at different adenosine receptor subtypes (A1 , A2A , A2B , and A3 ) and also good in vivo bronchospasmolytic activity against histamine aerosol-induced asthma in guinea pigs. Most of the compounds showed maximum affinity toward the A2A receptor subtype. The monosubstituted 3-aminoalkoxyl 8-phenyl xanthine with a aminodiethyl moiety (compound 12e) was found to be most potent A2A adenosine receptor ligand (Ki  = 0.036 µM) followed by disubstituted 4-aminoalkoxyl-3-methoxy-8-phenyl xanthine (Ki  = 0.050 µM) (compound 10a).

Corrosive Esophageal Strictures: From Dilatation to Replacement: A Retrospective Cohort Study.

Endoscopic dilatation is the recommended primary therapy for chronic corrosive esophageal strictures (ES), and surgery is reserved for failed dilatation. Through this study, we intend to analyze the efficacy and long-term outcomes of both endoscopic and surgical interventions in corrosive ES. A retrospective cohort analysis of patients with chronic corrosive ES, managed with endoscopic or surgical procedures at a tertiary teaching institute in North India from December 2009 to December 2016, was performed from a prospectively maintained database. The primary outcome measure was the absence of dysphagia following dilatation or surgery. During the study period, 64 patients with ES underwent surgical or endoscopic treatment. Associated gastric strictures and pharyngeal strictures were present in 39 (60%) and 22 patients (28.9%), respectively. The mean age was 28.8 years and mean BMI was 14.2 kg/m2. Acid was the most common corrosive substance. Endoscopic dilatation using Savary-Gilliard (SG) dilators was successful in achieving persistent symptom relief in 46 patients (71.8%) after a total of 358 sessions (mean number of dilatations were 5.2 ± 1.2) of dilatations over 2 years. The dilatation therapy failed in 18 patients (28.1%) including technical failures (15.6%), perforations (3.1%), refractory stricture (1.5%) and recurrent strictures (7.8%). Increasing stricture length (more than 6 cm) was associated with poor outcome of endoscopic dilatation (p < 0.001). Only eleven patients (17%) required esophageal replacement (resection: 0, bypass: 11) for failed dilatations including seven gastric pull-ups and four pharyngo-coloplasty. The stricture rate after surgery was 36.3% (4/11). The median follows up was 32 months. Endoscopic dilatation of corrosive ES is safe and effective therapy and should be the first-line therapy for these patients and surgery should be considered only in patients who have unsuccessful outcome following dilatation therapy.

A novel small molecule A2A adenosine receptor agonist, indirubin-3'-monoxime, alleviates lipid-induced inflammation and insulin resistance in 3T3-L1 adipocytes.

Saturated free fatty acid-induced adipocyte inflammation plays a pivotal role in implementing insulin resistance and type 2 diabetes. Recent reports suggest A2A adenosine receptor (A2AAR) could be an attractive choice to counteract adipocyte inflammation and insulin resistance. Thus, an effective A2AAR agonist devoid of any toxicity is highly appealing. Here, we report that indirubin-3'-monoxime (I3M), a derivative of the bisindole alkaloid indirubin, efficiently binds and activates A2AAR which leads to the attenuation of lipid-induced adipocyte inflammation and insulin resistance. Using a combination of in silico virtual screening of potential anti-diabetic candidates and in vitro study on insulin-resistant model of 3T3-L1 adipocytes, we determined I3M through A2AAR activation markedly prevents lipid-induced impairment of the insulin signaling pathway in adipocytes without any toxic effects. While I3M restrains lipid-induced adipocyte inflammation by inhibiting NF-κB dependent pro-inflammatory cytokines expression, it also augments cAMP-mediated CREB activation and anti-inflammatory state in adipocytes. However, these attributes were compromised when cells were pretreated with the A2AAR antagonist, SCH 58261 or siRNA mediated knockdown of A2AAR. I3M, therefore, could be a valuable option to intervene adipocyte inflammation and thus showing promise for the management of insulin resistance and type 2 diabetes.

Comparative evaluation of neodymium-doped yttrium aluminum garnet laser with nanocrystalline hydroxyapatite dentifrices and herbal dentifrices in the treatment of dentinal hypersensitivity.

BACKGROUND: The aim of this study was to compare and evaluate the efficacy of neodymium-doped yttrium aluminum garnet laser with and without herbal and nanohydroxyapatite dentifrices in management of dentinal hypersensitivity (DH). MATERIALS AND METHODS: A total of 180 patients who responded to air-blast test and cold-water test using verbal rating scale (VRS) were included in this study. The patients were randomly assigned to six groups (n = 30): control group (CG), scaling and root planning (SRP) + nanocrystalline hydroxyapatite dentifrices, SRP + nanocrystalline hydroxyapatite dentifrices + laser, SRP + herbal dentifrices, SRP + herbal dentifrices + laser, and SRP + laser. Each group was evaluated at baseline, 1 week, 1 month, and 6 months. In every visit of each patient, their clinical examination was done. RESULTS: Among all groups', repeated ANOVA measures and Kruskal-Wallis test was performed in which laser groups showed maximum reduction in DH in all indices while the CG showed minimum reduction in DH. The VRS values showed maximum reduction in SRP + nanocrystalline hydroxyapatite dentifrices + laser group with mean of 0.3 ± 0.5 and minimum reduction in CG with mean of 3.0 ± 0.5 (P < 0.001). CONCLUSION: Among all the groups, SRP + Nanocrystalline hydroxyapatite + Laser can be an effective treatment modality for DH.

Blumgart's technique of pancreaticojejunostomy: Analysis of safety and outcomes.

BACKGROUND: Blumgart's pancreaticojejunostomy (PJ) has been described with low pancreatic leak rates. This study aimed to evaluate our experience with this technique regarding the pancreatic leak and other perioperative outcomes. METHODS: We performed a single-center retrospective analysis of a cohort of 81 patients who underwent pancreaticoduodenectomy in our department from January 2011 to February 2018. The primary endpoint was the occurrence of a clinically relevant postoperative pancreatic fistula (CR-POPF) and analysis of its risk factors. RESULTS: The CR-POPF rate was 12.3%. Fistula risk score (FRS) was the only significant risk factor for the occurrence of overall POPF in multivariate analysis. However, none of the other factors including FRS was found to be significantly associated with CR-POPF risk. A strong positive correlation was found between the CR-POPF and the incidence of delayed gastric emptying, post-pancreatectomy hemorrhage and increased length of hospital stay. CONCLUSION: Blumgart's technique is a safe technique of pancreatico-enteric anastomosis with low rates of CR-POPF. CR-POPF with this technique is independent of most of the preoperative and intraoperative factors. Therefore, this technique can be used for all types of the pancreas with consistently good results.

Histone Deacetylase Inhibitors: A Prospect in Drug Discovery.

Cancer is a provocative issue across the globe and treatment of uncontrolled cell growth follows a deep investigation in the field of drug discovery. Therefore, there is a crucial requirement for discovering an ingenious medicinally active agent that can amend idle drug targets. Increasing pragmatic evidence implies that histone deacetylases (HDACs) are trapped during cancer progression, which increases deacetylation and triggers changes in malignancy. They provide a ground-breaking scaffold and an attainable key for investigating chemical entity pertinent to HDAC biology as a therapeutic target in the drug discovery context. Due to gene expression, an impending requirement to prudently transfer cytotoxicity to cancerous cells, HDAC inhibitors may be developed as anticancer agents. The present review focuses on the basics of HDAC enzymes, their inhibitors, and therapeutic outcomes.