XL1R-Net: Explainable AI-driven improved L1-regularized deep neural architecture for NSCLC biomarker identification.

BACKGROUND AND OBJECTIVE: Non-small cell lung cancer (NSCLC) exhibits intrinsic molecular heterogeneity, primarily driven by the mutation of specific biomarkers. Identification of these biomarkers would assist not only in distinguishing NSCLC into its major subtypes - Adenocarcinoma and Squamous Cell Carcinoma, but also in developing targeted therapy. Medical practitioners use one or more types of omic data to identify these biomarkers, copy number variation (CNV) being one such type. CNV provides a measure of genomic instability, which is considered a hallmark of carcinoma. However, the CNV data has not received much attention for biomarker identification. This paper aims to identify biomarkers for NSCLC using CNV data. METHODS: An eXplainable AI (XAI)-driven L1-regularized deep learning architecture, XL1R-Net, is proposed that introduces a novel modification of the standard L1-regularized gradient descent algorithm to arrive at an improved deep neural classifier for NSCLC subtyping. Further, XAI-based feature identification has been used to leverage the trained classifier to uncover a set of twenty NCSLC-relevant biomarkers. RESULTS: The identified biomarkers are evaluated based on their classification performance and clinical relevance. Using Multilayer Perceptron (MLP)-based model, a classification accuracy of 84.95% using 10-fold cross-validation is achieved. Moreover, the statistical significance test on the classification performance also revealed the superiority of the MLP model over the competitive machine learning models. Further, the publicly available Drug-Gene Interaction Database reveals twelve of the identified biomarkers as potentially druggable. The K-M Plotter tool was used to verify eighteen of the identified biomarkers with a high probability of predicting NSCLC patients' likelihood of survival. While nine of the identified biomarkers confirm the recent literature, five find mention in the OncoKB Gene List. CONCLUSION: A set of seven novel biomarkers that have not been reported in the literature could be investigated for their potential contribution towards NSCLC therapy. Given NSCLC's genetic diversity, using only one omics data type may not adequately capture the tumor's complexity. Multiomics data and its integration with other sources will be examined in the future to better understand NSCLC heterogeneity.

An explainable AI-driven biomarker discovery framework for Non-Small Cell Lung Cancer classification.

Non-Small Cell Lung Cancer (NSCLC) exhibits intrinsic heterogeneity at the molecular level that aids in distinguishing between its two prominent subtypes - Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Carcinoma (LUSC). This paper proposes a novel explainable AI (XAI)-based deep learning framework to discover a small set of NSCLC biomarkers. The proposed framework comprises three modules - an autoencoder to shrink the input feature space, a feed-forward neural network to classify NSCLC instances into LUAD and LUSC, and a biomarker discovery module that leverages the combined network comprising the autoencoder and the feed-forward neural network. In the biomarker discovery module, XAI methods uncovered a set of 52 relevant biomarkers for NSCLC subtype classification. To evaluate the classification performance of the discovered biomarkers, multiple machine-learning models are constructed using these biomarkers. Using 10-Fold cross-validation, Multilayer Perceptron achieved an accuracy of 95.74% (±1.27) at 95% confidence interval. Further, using Drug-Gene Interaction Database, we observe that 14 of the discovered biomarkers are druggable. In addition, 28 biomarkers aid the prediction of the survivability of the patients. Out of 52 discovered biomarkers, we find that 45 biomarkers have been reported in previous studies on distinguishing between the two NSCLC subtypes. To the best of our knowledge, the remaining seven biomarkers have not yet been reported for NSCLC subtyping and could be further explored for their contribution to targeted therapy of lung cancer.

Six-year study on peripheral venous catheter-associated BSI rates in 262 ICUs in eight countries of South-East Asia: International Nosocomial Infection Control Consortium findings.

BACKGROUND: Short-term peripheral venous catheter-associated bloodstream infection rates have not been systematically studied in Asian countries, and data on peripheral venous catheter-associated bloodstream infections incidence by number of short-term peripheral venous catheter days are not available. METHODS: Prospective, surveillance study on peripheral venous catheter-associated bloodstream infections conducted from 1 September 2013 to 31 May 2019 in 262 intensive care units, members of the International Nosocomial Infection Control Consortium, from 78 hospitals in 32 cities of 8 countries in the South-East Asia Region: China, India, Malaysia, Mongolia, Nepal, Philippines, Thailand, and Vietnam. For this research, we applied definition and criteria of the CDC NHSN, methodology of the INICC, and software named INICC Surveillance Online System. RESULTS: We followed 83,295 intensive care unit patients for 369,371 bed-days and 376,492 peripheral venous catheter-days. We identified 999 peripheral venous catheter-associated bloodstream infections, amounting to a rate of 2.65/1000 peripheral venous catheter-days. Mortality in patients with peripheral venous catheter but without peripheral venous catheter-associated bloodstream infections was 4.53% and 12.21% in patients with peripheral venous catheter-associated bloodstream infections. The mean length of stay in patients with peripheral venous catheter but without peripheral venous catheter-associated bloodstream infections was 4.40 days and 7.11 days in patients with peripheral venous catheter and peripheral venous catheter-associated bloodstream infections. The microorganism profile showed 67.1% were Gram-negative bacteria: Escherichia coli (22.9%), Klebsiella spp (10.7%), Pseudomonas aeruginosa (5.3%), Enterobacter spp. (4.5%), and others (23.7%). The predominant Gram-positive bacteria were Staphylococcus aureus (11.4%). CONCLUSIONS: Infection prevention programs must be implemented to reduce the incidence of peripheral venous catheter-associated bloodstream infections.

Six-year multicenter study on short-term peripheral venous catheters-related bloodstream infection rates in 204 intensive care units of 57 hospitals in 19 cities of India: International Nosocomial Infection Control Consortium (INICC) findings.

BACKGROUND: Short-term peripheral venous catheters-related bloodstream infections (PVCR-BSIs) rates have not been systematically studied in developing countries, and data on their incidence by number of device-days are not available. METHODS: Prospective, surveillance study on PVCR-BSI conducted from September 1, 2013 to May 31, 2019 in 204 intensive care units (ICUs), members of the International Nosocomial Infection Control Consortium (INICC), from 57 hospitals in 19 cities of India. We applied US INICC definition criteria and reported methods using the INICC Surveillance Online System. RESULTS: We followed 7,513 ICU patients for 296,893 bed-days and 295,795 short term peripheral venous catheter (PVC)-days. We identified 863 PVCR-BSIs, amounting to a rate of 2.91/1,000 PVC-days. Mortality in patients with PVC but without PVCR-BSI was 4.14%, and 11.59% in patients with PVCR-BSI. The length of stay in patients with PVC but without PVCR-BSI was 4.13 days, and 5.9 days in patients with PVCR-BSI. The micro-organism profile showed 68% of gram negative bacteria: Escherichia coli (23%), Klebsiella spp (15%), Pseudomonas aeruginosa (5%), and others. The predominant gram-positive bacteria were Staphylococcus aureus (10%). CONCLUSIONS: PVCR-BSI rates found in our ICUs were much higher than rates published from industrialized countries. Infection prevention programs must be implemented to reduce the incidence of PVCR-BSIs.

Prevalence of Minimal Hepatic Encephalopathy in Patients With Liver Cirrhosis: A Cross-Sectional, Clinicoepidemiological, Multicenter, Nationwide Study in India: The PREDICT Study.

BACKGROUND: The study aimed at assessing the prevalence and clinical profile of minimal hepatic encephalopathy (MHE) in patients with cirrhosis using neuropsychological assessment and at understanding the management practices of MHE in the Indian clinical setting. METHODS: This cross-sectional, clinicoepidemiological study conducted at 20 sites enrolled liver cirrhosis patients with Grade 0 hepatic encephalopathy according to West-Haven Criteria. Patients were subjected to mini-mental state examination and those with a score of ≥24 were assessed using psychometric hepatic encephalopathy score. Short Form-36 questionnaire was administered to assess the impact on health-related quality of life. RESULTS: Of the 1260 enrolled patients, 1114 were included in the analysis. The mean age was 49.5 years and majority were males (901 [81%]). The prevalence of MHE was found to be 59.7% (665/1114) based on the psychometric hepatic encephalopathy score of ≤-5. Alcohol-related liver disease was the most common etiology (482 [43.27%]) followed by viral infection (239 [21.45%]). Past smokers as well as those currently smoking were more likely to have MHE than nonsmokers. A significant association was found between tobacco chewing, smoking, alcohol consumption, diabetes, and the presence of MHE. Multivariable analysis revealed smoking as the only parameter associated with MHE. A total of 300 (26.9%) patients were on prophylaxis with lactulose/lactitol or rifaximin. These patients were less likely to have MHE as compared to those not on prophylaxis (odds ratio, 0.67; 95% confidence interval, 0.50-0.88; P = 0.005). CONCLUSION: The disease burden of MHE is quite substantial in patients with cirrhosis with no apparent cognitive defect. Smoking, whether past or current, has significant association with the presence of MHE. Although MHE has been shown to adversely affect quality of life, prophylaxis for MHE is not routinely practiced in the Indian setting.The study has been registered under clinical trials registry of India (CTRI/2014/01/004306).

Identification of brain regions associated with working memory deficit in schizophrenia.

Background: Schizophrenia, a severe psychological disorder, shows symptoms such as hallucinations and delusions. In addition, patients with schizophrenia often exhibit a deficit in working memory which adversely impacts the attentiveness and the behavioral characteristics of a person. Although several clinical efforts have already been made to study working memory deficit in schizophrenia, in this paper, we investigate the applicability of a machine learning approach for identification of the brain regions that get affected by schizophrenia leading to the dysfunction of the working memory. Methods: We propose a novel scheme for identification of the affected brain regions from functional magnetic resonance imaging data by deploying group independent component analysis in conjunction with feature extraction based on statistical measures, followed by sequential forward feature selection. The features that show highest accuracy during the classification between healthy and schizophrenia subjects are selected. Results: This study reveals several brain regions like cerebellum, inferior temporal gyrus, superior temporal gyrus, superior frontal gyrus, insula, and amygdala that have been reported in the existing literature, thus validating the proposed approach. We are also able to identify some functional changes in the brain regions, such as Heschl gyrus and the vermian area, which have not been reported in the literature involving working memory studies amongst schizophrenia patients. Conclusions: As our study confirms the results obtained in earlier studies, in addition to pointing out some brain regions not reported in earlier studies, the findings are likely to serve as a cue for clinical investigation, leading to better medical intervention.

Rehabilitation of Posterior Maxilla with Obturator Supported by Zygomatic Implants.

Prosthetic rehabilitation of atrophic maxilla and large maxillary defects can be done successfully by zygomatic implant-supported prosthesis. Zygomatic implants are an avant-garde to complex and invasive-free vascularised osteocutaneous flaps, distraction osteogenesis, and the solution to flap failures. A treated case of tuberculous osteomyelitis, with a class II (Aramany's classification) maxillary defect, reported to oral maxillofacial department, Government Dental College (RUHS-CODS). The defect in this group was unilateral, retaining the anterior teeth. The patient was previously rehabilitated with a removable maxillary obturator. Inadequate retention affected essential functions like speaking, mastication, swallowing, esthetics, and so on due to lack of sufficient supporting tissues. A fixed prosthetic rehabilitation of posterior maxillary defect was done with obturator supported with two single-piece zygomatic implants. At 1-year follow-up, the patient was comfortable with the prosthesis, and no further complaints were recorded.

Cardiotoxic Effects of Raw Opium.

While opioid drug toxicity and side effects of long-term opioid use during medical care are well studied, there is little information regarding effects of ingestion of raw opium. Characterization of the effects to a particular alkaloid is difficult since raw opium contains a number of alkaloids. Here, we present a case of poisoning due to ingestion of raw opium leading to severe myocardial suppression.

Disseminated Histoplasmosis with Oral Manifestation in an Immunocompetent Patient.

A case of disseminated histoplasmosis (DH) in a 60-year-old female patient is reported from Jaipur, Rajasthan, India. The patient presented with multiple papules on the skin surrounding the lips, face, torso, trunk, and back. She also complained of growth in the palate. Histoplasmosis was confirmed by biopsy and histopathology of skin and palatal lesions. This case report highlights the presenting features and occurrence of histoplasmosis in nonendemic region in India.

Transcatheter closure of ruptured sinus of Valsalva aneurysm in a pregnant woman.

Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly that is usually congenital, but may be acquired. They are usually asymptomatic unless they compress adjacent structures, develop thrombosis, or rupture. A ruptured SVA (RSVA) can lead to rapid hemodynamic deterioration and often needs to be addressed emergently. Surgical correction has traditionally been the treatment of choice for RSVA; however, lately they have been successfully closed percutaneously using various transcatheter devices. Few cases of RSVA during pregnancy have been reported which were conservatively or surgically managed. There is no documented case of transcatheter closure of RSVA during pregnancy. We report the first case of successful percutaneous device closure of RSVA using an Amplatzer duct occluder in a pregnant woman presenting with heart failure due to RSVA at 26 weeks of gestation. .

Management of the dental patient on anticoagulant medication: a review.

Patients taking anticoagulant medication pose a challenge for the clinician. Dentists are often required to manage bleeding as part of routine oral surgery or dental procedures, and altered hemostasis can lead to complications. Nevertheless, use of these medications is generally important for the patient's health and any alteration in the anticoagulant regimen may have untoward sequelae. In addition, several medications can affect the clotting mechanism, potentially compromising hemostasis. This article will review a variety of anticoagulant medications and the medical conditions that necessitate their use.

Pegylated interferon alfa-2b plus ribavirin for treatment of chronic hepatitis C.

AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus (HCV). METHODS: One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 µg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin (800 mg/d for ≤ 65 kg; 1000 mg/d for > 65-85 kg; 1200 mg/d for > 85-105 kg; 1400 mg/d for > 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed. RESULTS: Eighty-two patients (35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response (RVR): while the figures were 74.1% for early virologic response (EVR) and 44.4% for sustained virologic response (SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events (SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication. CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.

Optical coherence tomography guided PCI - initial experience at Apollo Health City, Jubilee Hills, Hyderabad.

BACKGROUND: The capability of OCT to examine the structure of the arterial wall before or after PCI is superior to those of other imaging modalities. Therefore the application of OCT during PCI seems logical and has the potential to enhance our performance during the PCI procedures. METHODS: OCT was performed in fifty-two patients out of which, 45 patients underwent PCI. Out of these 45 patients, in 25 patients both pre and post PCI OCT assessment was done. In 20 patients only post PCI OCT assessment was done. In seven patients PCI was not done due to nonsignificant obstruction, these seven patients were not included in final analysis. RESULTS: Over all OCT leads to management changes in 65% of the time it was used. Alteration of stent length was done in 56% of the cases when evaluated pre PCI. Alteration of stent diameter was done in 36% cases when evaluated pre PCI. Treatment of malapposition was done in 24% of total cases. Further balloon dilatation for vessel expansion was done in 15% of total cases. In one case left main stenting was done after proximal edge dissection. CONCLUSION: OCT makes better visualization of plaque, thrombus, stent malapposition, dissection, plaque prolapse and helps in optimization of PCI results. More extensive, long-term studies will be needed to assess the prognostic implications of these findings.

The radix entomolaris and radix paramolaris: an endodontic challenge.

Success of endodontic treatment depends on the proper identi-fication of all the canals, thorough chemomechanical preparation followed by three-dimensional obturation with hermetic seal. Failure of any of these steps may occur due to unusual tooth morphology. Usually mandibular molars have two roots with three canals but in few teeth, the number of roots and canals vary. The variation in the number of roots, if extra root located lingually called radix entomolaris (RE) or located bucally called radix paramolaris (RP). This article presents successful endo-dontic treatment of two mandibular frst molars with extra roots one is with radix entomolaris and other is with radix paramolaris, both of which are rare microstructures.

Mandibular first molar with Vertucci type I canal confguration diagnosed with the help of cone beam computed tomography: a rare case report.

The knowledge of root canal morphology and the existing anatomical variations is essential for successful endodontic therapy. This report presents an extraordinary case of unusual tooth morphology involving the mandibular first molar with a single root and a single canal in a patient. Endodontic treatment of the affected tooth 36 was performed. Cone beam computed tomography (CBCT) images confirmed our diagnostic and therapeutic measures after endodontic management of the teeth. This morphologic variation has been reported once in the literature. The availability of three-dimensional images further provided the opportunity for the precise description of the anatomy of mandibular first molar with single roots and single canals.

Fibreoptic bronchoscopy without sedation: Is transcricoid injection better than the "spray as you go" technique?

AIM: The aim of the study was to compare transcricoid injection with spray as you go technique for diagnostic fibreoptic bronchoscopy, to perform the procedure without sedation and to record any complication or side effects. METHODS: Sixty patients belonging to the age group 20-70 years, undergoing diagnostic bronchoscopy over a period of 6 months, were randomly selected and divided into two groups alternatively to receive 3 ml of 4% lignocaine by a single transcricoid puncture (group I) or 2 ml of 4% lignocaine instilled through the bronchoscope on to the vocal cords and further 1 ml of 2% lignocaine into each main bronchus (group II). Additional dose of lignocaine as required was given in both the groups. All patients were given intramuscular atropine 0.6 mg, 20 min before the procedure. Nebulisation with 3 ml of 4% lignocaine was given to all patients. The time from nasal insertion of the bronchoscope to reach the carina was recorded, and the total dose of lignocaine required in both the groups was calculated and compared. The cough episodes during the procedure, systolic blood pressure, and pulse rate were compared before the procedure and 5 min after the procedure in both the groups. A0-10 visual analogue scale (VAS) was used to assess discomfort 30 min after the procedure. RESULTS: The time to reach carina was more in group II (P<0.02), and cough episodes were also more in group II (P<0.05) than in group I. The vitals before the procedure were comparable in both the groups, but 5 min after the procedure the vitals were more stable in group I than in group II, and the total dose of lignocaine required in group II was more than in group I (P<0.001). However, the VAS score was comparable in both the groups. CONCLUSION: Transcricoid puncture for diagnostic bronchoscopies without sedation was associated with no complication and discomfort and required lesser dose of local anaesthetic with more stable vitals and good conditions for bronchoscopists.

Synthesis, characterization and antimicrobial activities of some mixed ligand complexes of Co(II) with thiosemicarbazones and N-protected amino acids.

The reaction of cobalt(II) chloride with a new class of thiosemicarbazones viz; cis-3,7-dimethyl-2,6-octadienthiosemicarbazone(CDOTSC; L(1)H) and 3,7-dimethyl-6-octenethiosemicarbazone (DOTSC; L(2)H) and N-phthaloyl derivative of DL-glycine(A(1)H), L-alanine(A(2)H) or L-valine(A(3)H) in 1:1:1 molar ratio in dry refluxing ethanol have been studied. All the isolated complexes have the general composition [Co(L)(A)]. Tentative structures are proposed for these complexes based upon elemental analysis, electrical conductances, magnetic moment, molecular weight determination and spectral (IR, electronic) studies.The ligands and Co(II) complexes have been tested for their antibacterial and antifungal activities against three bacterial strains S. aureus, B. subtilis, E. coli and two fungal strains F. moniliformae and M. phaseolina. Attempts have been made to establish a correlation between the antibacterial and antifungal activity and the structures of products.