Publications by authors named "Siddharth Sharma"

91 Publications

Correlation of Serum Selenium in Asthma Patients with Severity of the Disorder.

Biol Trace Elem Res 2022 Jan 13. Epub 2022 Jan 13.

School of Energy and Environment, Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, India.

Asthma is characterized by reversible airway obstruction, increased bronchial hyper-responsiveness and chronic inflammation, as well as higher levels of oxidative stress mainly due to decreased antioxidant defenses. Our primary aim was to investigate the correlation of serum selenium (Se) levels with the severity of asthma across gender, age, family history, and prevalence from childhood. Selenium levels in blood samples in 103 asthmatic patients and 103 healthy individuals were evaluated. The obtained data indicated that the mean serum Se levels in asthma patients were found to be twofold lower as compared to the controls (p < 0.001). However, there were no significant differences in the asthmatic patients when gender and age were considered. Patients characterized by family history of asthma and inhaler usage had 8% and 7% lower serum Se concentrations, although the difference was only border significant (p = 0.05). Multiple regression analysis demonstrated a significant inverse association of inhaler usage (β =  - 0.226; p < 0.001) with serum Se levels even after adjustment for asthma severity (β =  - 0.644; p < 0.001). While this report clearly necessitates a more detailed study, it is plausible that Se deficiency leads to impaired immune response, and therefore, Se supplementation might modulate oxidative stress in the lung and could potentially alleviate asthma pathophysiology.
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http://dx.doi.org/10.1007/s12011-022-03096-8DOI Listing
January 2022

Association of gene polymorphisms toward lung cancer susceptibility and prognosis in North Indian patients treated with platinum-based chemotherapy.

Pharmacogenomics 2022 01 16;23(2):97-118. Epub 2021 Dec 16.

Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala, India.

The present study has been carried out to evaluate the association of the N-acetyl transferase 2 () variants in North Indian lung cancer patients and healthy controls. Furthermore, we have also determined the effect of the polymorphic variants of the gene on the clinical outcomes and overall survival among lung cancer (LC) subjects treated with platinum-based doublet chemotherapy. This case-control study comprised a total of 550 cases and 550 healthy controls. The genotyping was carried out using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and the statistical analysis was carried out using MedCalc. There was a lack of any significant association for both 590G>A and 803A>G polymorphisms toward risk for LC, but 857G>A polymorphism exhibited a risk toward LC (p = 0.005). Whereas, variant alleles for the 481C>T polymorphism had a decreased risk for LC (p = 0.0003). Further, 857G>A polymorphism conferred a positive association between genotype and ADCC (p = 0.001) and 481C>T polymorphism had a decreased risk for SQCC (OR = 0.39, p = 0.0006) and SCLC (p = 0.001) subjects. The smokers carrying mutant genotype for the 481C>T polymorphism had a decreased risk toward LC (p < 0.0001) even in light (p = 0.002) as well as heavy smokers (p = 0.001). In case of females, 2.59-fold and 3.66-fold increased risk of LC development was observed in subjects with intermediate and slow acetylator for the 857G>A polymorphism. Whereas, in case of males this polymorphism depicts a reduced risk for LC. On the other hand, 803A>G depicted a 2.82-fold risk of LC in case of female subjects who were slow acetylators. Our study exhibits a significant difference in the overall haplotype distribution between cases and controls. In our study overall, (857G>A, 481C>T, 803A>G) was found to be best model, but was not significant using MDR. Considering the CART results 481C>T polymorphism came out to be the most significant factor in determining the LC risk. For the 803A>G polymorphism, a threefold odds of lymph node invasion were observed for mutant genotype, the recessive model exhibited an odds ratio of 2.8. 590G>A appears to be a potential prognostic factor for OS of SCLC patients after irinotecan therapy as the survival time for such patients was better. These results suggest that variant genotype for 590G>A and 803A>G was not found to modulate risk toward LC, but 857G>A polymorphism exhibited a risk toward LC and 481C>T polymorphism had a decreased risk for LC. 590G>A appears to be a potential prognostic factor for OS of SCLC patients after irinotecan therapy and 481C>T came out to be significant factor using CART.
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http://dx.doi.org/10.2217/pgs-2021-0080DOI Listing
January 2022

Identification of SNPs in hMSH3/MSH6 interaction domain affecting the structure and function of MSH2 protein.

Biotechnol Appl Biochem 2021 Nov 27. Epub 2021 Nov 27.

Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala, Punjab, India.

MutS homolog 2 (MSH2) is a mismatch repair gene that plays a critical role in DNA repair pathways, and its mutations are associated with different cancers. The present study aimed to find out the single nucleotide polymorphisms (SNPs) of MSH2 protein associated with causing structural and functional changes leading to the development of cancer with the help of computational tools. Four different tools for predicting deleterious SNPs (SIFT, PROVEAN, PANTHER, and PolyPhen), two tools each for identifying disease association (PhD-SNP and SNP&GO) and estimating stability (I-mutant and MUPro) were employed. Homology modeling, energy minimization, and root mean square deviation calculation were used to estimate structural variations. Twenty-seven SNPs and five SNPs (double amino acid change) were identified based on a consensus approach that might be associated with the structural and functional change in MSH2 protein. Molecular docking reveals that six SNPs affect the interaction of MSH2 and MSH6. Twelve identified SNPs were reported to be linked with hereditary nonpolyposis, colorectal cancer, and Lynch syndrome. Further, selected SNPs need to be validated in an in vitro system for their precise association with cancer predisposition.
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http://dx.doi.org/10.1002/bab.2295DOI Listing
November 2021

ATP binding cassette transporters and cancer: revisiting their controversial role.

Pharmacogenomics 2021 12 16;22(18):1211-1235. Epub 2021 Nov 16.

Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala, India.

The expression of ATP-binding cassette transporter (ABC transporters) has been reported in various tissues such as the lung, liver, kidney, brain and intestine. These proteins account for the efflux of different compounds and metabolites across the membrane, thus decreasing the concentration of the toxic compounds. ABC transporter genes play a vital role in the development of multidrug resistance, which is the main obstacle that hinders the success of chemotherapy. Preclinical and clinical trials have investigated the probability of overcoming drug-associated resistance and substantial toxicities. The focus has been put on several strategies to overcome multidrug resistance. These strategies include the development of modulators that can modulate ABC transporters. This knowledge can be translated for clinical oncology treatment in the future.
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http://dx.doi.org/10.2217/pgs-2021-0116DOI Listing
December 2021

GSTP1 polymorphism among North Indian lung cancer patients treated using monotherapy and poly-pharmacy.

Hum Exp Toxicol 2021 Dec 15;40(12_suppl):S739-S752. Epub 2021 Nov 15.

Department of Biotechnology, 29080Thapar Institute of Engineering & Technology, Patiala, India.

Background: Genetic polymorphism within the P1 isoenzyme of the Glutathione-S-Transferase (GST) family is found to modulate and alter the enzyme activity of GSTP1 protein and thus may result in a change of sensitivity to platinum-based chemotherapy. We investigated the relationship between polymorphisms and overall survival, treatment response, and for both hematological and non-hematological toxicity of advanced North Indian lung cancer patients undergoing platinum-based double chemotherapy.

Methods: The polymorphism of GSTP1 North Indian lung cancer patients was assessed by polymerase chain reaction-restriction fragment length polymorphism. A total of 682 lung cancer patients were enrolled in the study, and it was observed that patients who were carrying both the mutant alleles () for the polymorphism showed a higher trend of median survival time (MST) as compared to the patients bearing the wild type of genotype ) (MST = 8.30 vs. 7.47, = 0.56). Based on toxicity profiling, we observed that lung cancer patients with the mutant genotype of GSTP1 had an increased risk of leukopenia (OR = 2.41; 95% CI = 1.39-4.18, = 0.001) as compared to subjects carrying both copies of the wild alleles (Ile/Ile). Our data suggested that patients with heterozygous genotype (Ile/Val) had a 2.14-fold increased risk of developing severe anemia (OR = 2.14, 95% CI = 0.97-4.62, = 0.03). Our data also showed that in small cell lung carcinoma (SCLC) patients' polymorphism of was associated with thrombocytopenia (χ2 test = 7.32, = 0.02).

Conclusions: Our results suggest that GSTP1 IleVal polymorphism could be a predictive biomarker for hematological toxicity, like leukopenia and anemia, but not thrombocytopenia or neutropenia.
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http://dx.doi.org/10.1177/09603271211059496DOI Listing
December 2021

polymorphism as a predictive biomarker for gastrointestinal and hematological toxicity in North Indian adenocarcinoma patients.

J Chemother 2021 Nov 3:1-15. Epub 2021 Nov 3.

Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala, India.

In the present study, we investigated the relationship between the methylenetetrahydrofolate reductase (MTHFR) and polymorphisms and overall survival, toxicity and treatment response for North Indian adenocarcinoma patients. The polymorphisms of MTHFR gene in north Indian adenocarcinoma patients were assessed by PCR-RFLP. Our data observed that patients with mutant genotype () for 1298 ) polymorphism showed higher trend of median survival time compared to patients bearing the wild type genotype () (MST= 13.93 vs. 7.97, p=0.12). Further, we observed patients with the heterozygous genotype for polymorphism had 12-fold risk of diarrhea (AOR =12.54, 95% CI = 1.54-101.86, p=0.018). The patients with heterozygous genotype () of the polymorphism had 5.34-fold increased risk of developing neutropenia (AOR=5.34, 95% CI=1.49-19.06, p=0.009). Our results suggest that MTHFR polymorphisms are associated with hematological toxicity. polymorphism might impact the development of pemetrexed and platinum-related toxicities but not as a clinical predictor of efficiency.
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http://dx.doi.org/10.1080/1120009X.2021.1997008DOI Listing
November 2021

Electrochemical metal- and oxidant-free synthesis of S-thiocarbamates.

Org Biomol Chem 2021 Nov 10;19(43):9491-9500. Epub 2021 Nov 10.

Department of Chemistry, Mohanlal Sukhadia University, Udaipur, 313001, India.

An expeditious synthetic strategy to access functionalized S-thiocarbamates was developed in good to excellent yields and with high current efficiencies. Readily available isocyanides and thiols were used as the starting materials under simple metal- and oxidant-free reaction conditions avoiding an inert atmosphere. The practical application of the present methodology was achieved by electrochemical synthesis of the herbicides prosulfocarb and pebulate. Furthermore, continuous electrochemical flow conditions using a graphite/Pt flow cell were used to obtain S-thiocarbamate compounds on a gram scale within a residence time of 35 min.
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http://dx.doi.org/10.1039/d1ob01701bDOI Listing
November 2021

Genetic polymorphisms in the  gene in relation to tobacco smoking: role in lung cancer susceptibility and survival in north Indian patients with lung cancer undergoing platinum-based chemotherapy.

Future Oncol 2021 Dec 21;17(35):4925-4946. Epub 2021 Oct 21.

Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala 147004, India.

Epoxide hydrolase is involved in oxidative defenses and is responsible for the activation of carcinogens. The relationship between EPHX1 polymorphisms (TyrHis and HisArg) and overall survival (OS) and lung cancer (LC) risk was investigated. The study comprised 550 cases and 550 controls. Genotyping and statistical analysis were applied. The variant genotypes of EPHX1 polymorphisms exhibited no association with LC risk. The TyrHis polymorphism exhibited twofold increased odds of lymph node invasion (p = 0.04). The Tyr/His genotype is a risk factor for smokers. Subjects carrying the combined genotype for HisArg showed better median survival time (MST) and the heterozygous genotype revealed better MST in the case of small-cell lung cancer (SCLC; 11.30 vs 6.73 months; log-rank test: p = 0.02). The heterozygous genotype (His139Arg) had longer MST in patients receiving cisplatin/carboplatin and irinotecan (11.30 vs 7.23; log-rank test: p = 0.007) The TyrHis polymorphism is associated with LC risk in smokers and is a potential prognostic factor for OS in patients with SCLC after irinotecan.
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http://dx.doi.org/10.2217/fon-2021-0412DOI Listing
December 2021

Early versus delayed thromboprophylaxis with LMWH in pelvic-acetabular trauma- a prospective study.

Injury 2021 Oct 2. Epub 2021 Oct 2.

Professor, Department of Radiodiagnosis, PGIMER, Chandigarh, INDIA.

Background: Delayed presentation of pelvic-acetabular fractures is a common scenario in developing countries and there is usually a delay of more than 24 h in their presentation.

Objectives: We aim to comparatively analyse early(<24 h) versus delayed (>24 h) thromboprophylaxis with low molecular weight heparin (LMWH) in prevention of deep venous thrombosis (DVT) in Pelvic Acetabular fractures.

Methods: Patients of pelvic-acetabular fractures who presented during 1 year of study period were divided into 2 groups after exclusion of patients with contraindications for thromboprophylaxis. Group A included patients who received LMWH prophylaxis within 24 h of injury. Group B included patients who received LMWH prophylaxis after 24 h of injury. All patients underwent CT venography at day 14 and were followed up with doppler ultrasound on 4th and 8th week.

Results: 110 patients with pelvic-acetabular fractures were included after exclusion of 61 patients. 4 out of 29 patients in group A (13.8%) and 12 out of 81 patients (14.8%) in group B developed DVT. There was no significant difference in incidence of DVT between Group A and B (P value-0.893).

Conclusion: There was no difference between early and delayed thromboprophylaxis with LMWH in pelvic-acetabular trauma.
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http://dx.doi.org/10.1016/j.injury.2021.09.047DOI Listing
October 2021

Novel naphthyl based 1,2,4-trioxanes: Synthesis and in vivo efficacy in the Plasmodium yoelii nigeriensis in Swiss mice.

Bioorg Med Chem Lett 2021 11 20;51:128372. Epub 2021 Sep 20.

Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector 10 Jankipuram Extension Sitapur Road, Lucknow 226031, India; Department of Chemistry, Banasthali University, Banasthali Newai 304022, Rajasthan, India. Electronic address:

A new series of 1,2,4-trioxanes 9a1-a4, 9b1-b4, 10-13 and 9c1-c4 were synthesized and evaluated against multidrug-resistant Plasmodium yoelii nigeriensis in Swiss mice via oral and intramuscular (i.m.) routes. Adamantane-based trioxane 9b4, the most active compound of the series, provided 100% protection to the infected mice at the dose 48 mg/kg × 4 days and 100% clearance of parasitemia at the dose 24 mg/kg × 4 days via oral route. Adamantane-based trioxane 9b4, is twice active than artemisinin. We have also studied the photooxygenation behaviour of allylic alcohols 6a-b (3-(4-alkoxynaphthyl)-but-2-ene-1-ols) and 6c (3-[4-(tert-butyl-dimethyl-silanyloxy)-naphthalen-1-yl]-but-2-en-1-ol). Being behaving as dienes, they furnished corresponding endoperoxides, while behaving as allylic alcohols, they yielded β-hydroxyhydroperoxides. All the endoperoxides (7a-c) and β-hydroxyhydroperoxides (8a-c) have been separately elaborated to the corresponding 1,2,4-trioxanes, except from endoperoxide 7c. It is worthy to note that TBDMS protected naphthoyl endoperoxide 7c unable to deliver 1,2,4-trioxane, which demonstrated the strength of the O-Si bond is not easy to cleave under acidic condition.
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http://dx.doi.org/10.1016/j.bmcl.2021.128372DOI Listing
November 2021

Synthesis of novel 1,2,4-trioxanes and antimalarial evaluation against multidrug-resistant Plasmodium yoelii nigeriensis.

Bioorg Med Chem Lett 2021 10 6;49:128305. Epub 2021 Aug 6.

Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India; Department of Chemistry, Banasthali University, Banasthali Newai 304022, Rajasthan, India. Electronic address:

Malaria epidemics represent one of the life-threatening diseases to low-income lying countries which subsequently affect the economic and social condition of mankind. In continuation in the development of a novel series of 1,2,4-trioxanes 13a1-c1, 13a2-c2, and 13a3-c3 have been prepared and further converted into their hemisuccinate derivatives 14a1-c1, 14a2-c2, and 14a3-c3 respectively. All these new compounds were evaluated for their antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in mice by both oral and intramuscular (im) routes. Hydroxy-functionalized trioxane 13a1 showed 80% protection and its hemisuccinate derivative 14a1 showed 100% protection at a dose of 48 mg/kg × 4 days by both routes, which is twice active than artemisinin by oral route.
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http://dx.doi.org/10.1016/j.bmcl.2021.128305DOI Listing
October 2021

Genetic polymorphism of variant in the gene is associated with reduced susceptibility to lung cancer in North Indian population.

Xenobiotica 2021 Sep 17;51(9):1071-1080. Epub 2021 Aug 17.

Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala, India.

Sulfotransferases (SULTs) are phase II detoxification enzymes that is involved in the biotransformation of many compounds including tobacco carcinogens. A polymorphism in the S () gene results in reduced enzyme activity.We investigated the association between the (Arg/His) genotype and lung cancer (LC). This case-control study comprised of 550 cases and controls, matched on age, gender and smoking status.The variant genotype exhibited no association with LC risk, even after stratification on basis of histological subtypes. Male LC patients carrying the variant allele () did not exhibit an increased risk towards LC. Smokers harbouring the genotype did demonstrate a reduced risk towards LC (AOR = 0.70; ). Furthermore, the LC subjects who were heavy smokers and harbouring the genotype (AOR = 0.28; ) did not show a genetic predisposition towards LC susceptibility. The subjects who smoked pack years of above 40 and carrying the (AOR = 0.28; ) genotype were found to have a reduced risk for LC. Furthermore, 473 subjects were analysed in regards to overall survival, wherein the genotype exhibited better OS than genotype (11.30 vs. 8.07 months).This study provides evidence of no genetic predisposition towards LC risk associated with polymorphism in relation to tobacco smoking.
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http://dx.doi.org/10.1080/00498254.2021.1963008DOI Listing
September 2021

Association of polymorphism with clinical outcomes and survival of lung cancer patients treated with platinum chemotherapy.

Per Med 2021 07 11;18(4):333-346. Epub 2021 May 11.

Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala, India.

The study was carried out to evaluate the association of polymorphism in North Indian lung cancer (LC) patients. We determined the effect of this polymorphic variant on the survival of LC patients. This case-control study comprised a total of 1100 subjects. The genotyping was carried out using PCR-RFLP and statistical analysis was carried out. The variant TT genotype exhibited 3.5-fold higher odds in subjects with stage III (p = 0.0006), fivefold higher odds of lymph-node invasion (p = 0.007) and an odd of <1 in case of metastasis (p = 0.0028). Patients possessing TT genotype and administered with paclitaxel, exhibited a poor survival (3.57 vs 12.20 months; hazard ratio = 7.95; p = 0.0098). These results suggest that variant genotype was not found to modulate risk toward LC. However, the variant genotype was found to be strongly correlated with stage III LC, lymph node invasion and was found to be positively correlating with metastasis.
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http://dx.doi.org/10.2217/pme-2020-0119DOI Listing
July 2021

UGT1A1 Gene Polymorphisms in Patients with Small Cell Lung Cancer Treated with Irinotecan-Platinum Doublet Chemotherapy and Their Association with Gastrointestinal Toxicity and Overall Survival.

Oncologist 2021 08 12;26(8):701-713. Epub 2021 Apr 12.

Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Background: Irinotecan (CPT11) is an important drug for small cell lung cancer (SCLC) chemotherapy (CTx). UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms can influence CPT11-related toxicity. This study aimed to assess prevalence of UGT1A1 polymorphisms and their association with clinical outcomes in patients with SCLC on CPT11-CTx.

Methods: An observational cohort of treatment-naïve patients with SCLC was given CPT11-platinum doublet at a referral center in North India over 3 years. Clinical outcomes assessed were hematological and gastrointestinal toxicity (Common Terminology Criteria for Adverse Events, version 3.0), response rates (RECIST), and overall survival (OS). Peripheral blood was drawn from all enrolled patients just prior to CPT11-CTx initiation, and genomic DNA was isolated. Genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism for UGT1A1*7, UGT1A1*6, and UGT1A1*27 and by PCR-DNA sequencing for UGT1A1*28. Patients were classified as homozygous wild-type (WT/WT), heterozygous mutant (WT/M), or homozygous mutant (M/M) for each polymorphism assessed.

Results: Of 140 patients enrolled, no mutant alleles were found for UGT1A1*27 or UGT1A1*7. Frequency of UGT1A1*6 polymorphisms (n = 111) was 89.2% for WT/WT, 8.1% for WT/M, and 2.7% for M/M. For UGT1A1*28 (n = 102), this was 41.2% for WT/WT, 43.1% for WT/M, and 15.7% for M/M. UGT1A1*6 WT/WT patients tolerated >95% predicted CPT11 dose more frequently (59.6% vs. 25.0% in WT/M-M/M combined group; p = .026). The UGT1A1*6 WT/M-M/M group also experienced severe (grade ≥3) diarrhea (41.7% vs. 17.2% in WT/WT; p = .044) and mucositis (41.7% vs. 8.1% in WT/WT; p = .005) more frequently. On multivariate logistic regression analysis, UGT1A1*6 WT/M-M/M status was the only variable associated with occurrence of both mucositis (odds ratio [OR], 10.4) and severe diarrhea (OR, 4.8). UGT1A1*28 WT/M-M/M patients had better OS (320 days [95% confidence interval, 203-437] vs. 216 days [95% confidence interval, 140-292] in WT/WT group; p = .047). On multivariate Cox proportional hazards analysis, UGT1A1*28 WT/M-M/M status was independently associated with better OS (hazard ratio, 0.35), whereas lack of objective radiological response, moderate/heavy smoking, and increasing age were associated with worse OS.

Conclusion: UGT1A1*6 and UGT1A1*28 polymorphisms were associated with increased gastrointestinal toxicity and improved OS, respectively, in North Indian patients with SCLC receiving CPT11-CTx.

Implications For Practice: UGT1A1 gene polymorphisms are known to influence irinotecan-related toxicity. In this prospective cohort study of patients with small cell lung cancer receiving first-line irinotecan-platinum chemotherapy, the prevalence of UGT1A1*6 polymorphisms was found to be 10.8% UGT1A1*6 and 58.8% UGT1A1*28 homo/heterozygous mutant, respectively. UGT1A1*6 homo/heterozygous mutant status was associated with severe diarrhea and mucositis. UGT1A1*28 homo/heterozygous mutant status was independently associated with improved overall survival.
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http://dx.doi.org/10.1002/onco.13757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342561PMC
August 2021

Assessment of Bone Quality Using Radiogrammetric Parameters of Proximal Humerus in India: Defining the Osteoporotic Fracture Risk Limit Value and its Reliability.

Indian J Orthop 2020 Dec 9;54(Suppl 2):307-315. Epub 2020 Aug 9.

Department of Orthopaedic Surgery, Maulana Azad Medical College and Associated Lok Nayak Hospital, c/o Mr Raj Kumar Arora, B-253, Second floor, New Delhi, 110002 India.

Background: World health organization (WHO) has defined osteoporosis clinically on the basis of bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DXA) scan and the presence of fractures. This facility is expensive and not readily available in majority of the centers in India. The authors have attempted to study defined measurements on radiographs (radiogrammetric parameters) to diagnose osteoporosis in Indian population.

Patients And Methods: We prospectively studied 200 proximal humerus radiographs for measuring radiogrammetric parameters and divided into Group A and B ( = 100 in each group). Group A involved patients with age < 50 years and without any illness affecting bone quality. Group B involved patients with age > 50 years and sustained acute osteoporotic fractures of distal radius/ anterior wedge vertebral fracture/intertrochanteric fracture following trivial trauma. Three parameters (cortical thickness, cortical index and deltoid tuberosity index) were measured by 3 observers at 2 different occasions.

Results: The mean age of patients was 37.87 years and 58.38 years for group A and B, respectively. The 'cortical thickness' of the proximal humerus diaphysis had the mean value for Group A and B to be 0.4 ± 0.07 cm and 0.33 ± 0.06 cm respectively. The mean values for the 'cortical index' of proximal humerus came out to be 0.4 ± 0.07 for group A and 0.32 ± 0.06 for group B. The 'deltoid tuberosity index' measurements showed the mean values for group A and B were 1.81 ± 0.23 and 1.55 ± 0.16, respectively. Inter-observer reliability for single measures was excellent for deltoid tuberosity index (ICC 0.8077) and good for cortical thickness (ICC 0.7032) and cortical index (ICC 0.7357). Observer 1 had excellent intra-observer reliabilities for all the three parameters. Observer 2 and 3 had excellent reliability for deltoid tuberosity index and good intra-observer reliability for cortical thickness and cortical index. The cortical thickness had a cut off of ≤ 0.372 cm with a sensitivity of 86.02 and specificity of 82.12. The cortical index had a cut off of ≤ 0.378 with a sensitivity of 89.16 and specificity of 84.22. The deltoid tuberosity index had a cut off of ≤ 1.684 with a sensitivity of 96.61 and specificity of 84.08.

Conclusion: The outcome of this study is likely to help in early diagnosis of osteoporosis at the community level in the absence of DXA scan as it identifies threshold values for radiogrammetric parameters which can be a predictor of the osteoporosis. The deltoid tuberosity index was found to be the most suitable of these parameters.
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http://dx.doi.org/10.1007/s43465-020-00224-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609647PMC
December 2020

Efficacy of Microplates versus Miniplates in the Management of Maxillofacial Fractures.

Ann Maxillofac Surg 2020 Jan-Jun;10(1):31-36. Epub 2020 Jun 8.

Department of Oral and Maxillofacial Surgery, Institute of Dental Studies and Technologies, Modinagar, Uttar Pradesh, India.

Introduction: Increased facial trauma has led to advances in techniques of internal fixation, improvements in plating system, refinements in exposure of facial skeleton fueling the rapid use of internal fixation for the management of facial fractures. Evaluating 40 patients with confirmed midfacial (Le Fort I and II) and mandibular fractures, this study presents the efficacy of microplate in comparison with miniplate in terms of load bearing capacity, stability at the fracture site and postoperative palpability.

Objectives: To evaluate the efficacy of microplates in comparison with miniplates in maxillofacial trauma.

Materials And Methods: Study sample consists 40 subjects, 20 each in two groups clinically and radiographically diagnosed with Group 1 (maxillary) and Group 2 (mandibular fractures) which were subdivided into 10 each treated with miniplate and microplate respectively. Postoperatively, stability of fracture, bite force, need for postop MMF, pain, infection, wound dehiscence, mouth opening, occlusion and palpability was noted. All cases have been evaluated clinically for various parameters for minimum of 3 months to assess any postoperative complications.

Results: We found microplates are stable enough and have adequate load bearing capacity. Due to close adaptability and less hardware, postoperative palpability is less but larger sample study with long term follow up is necessary to conclude its efficacy in load bearing fracture sites.
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http://dx.doi.org/10.4103/ams.ams_30_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433951PMC
June 2020

Electrochemical Synthesis of Carbodiimides via Metal/Oxidant-Free Oxidative Cross-Coupling of Amines and Isocyanides.

Org Lett 2020 Mar 6;22(6):2323-2327. Epub 2020 Mar 6.

Department of Chemistry, Mohanlal Sukhadia University, Udaipur, 313001, India.

This work discloses an electrochemical oxidative cross-coupling of amines with aryl and aliphatic isocyanides. In an undivided cell, the reaction proceeds without involving any transition-metal catalyst, oxidant, or toxic reagents providing carbodiimides in good yields, thereby circumventing stoichiometric chemical oxidants, with H as the only byproduct. Moreover, carbodiimides were in situ converted into unsymmetrical ureas in moderate to good yields using an electricity ON-OFF strategy.
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http://dx.doi.org/10.1021/acs.orglett.0c00510DOI Listing
March 2020

Efficacy of two-point fixation in the management of zygomatic complex fractures - A prospective clinical study.

Natl J Maxillofac Surg 2019 Jul-Dec;10(2):223-227. Epub 2019 Nov 12.

Department of Oral and Maxillofacial Surgery TMU, Moradabad, Uttar Pradesh, India.

Introduction: Anatomic disfigurement caused by zygomatic fracture warrants intervention tore establish facial symmetry. It is most predictably restored to pre morbid condition by ORIF.

Aim: To evaluate the efficacy of 2 point fixation in Zygomaticomaxillary complex fractures.

Material And Method: 20 patients with established ZMC fractures were operated using two point fixation method and followed up for upto 3 months.

Results: 2 point fixation revealed satisfactory functional and esthetic results.

Conclusion: 2 point fixation offers efficient outcome as compared to other modalities of management of ZMC.
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http://dx.doi.org/10.4103/njms.NJMS_49_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883889PMC
November 2019

Efficacy of hybrid implants in oral and maxillofacial surgery: A clinical prospective study.

Natl J Maxillofac Surg 2019 Jul-Dec;10(2):175-181. Epub 2019 Nov 12.

Department of Oral and Maxillofacial Surgery, Institute of Dental Studies and Technologies, Modinagar, Uttar Pradesh, India.

Aim: The present study was aimed to evaluate the efficacy of hybrid implants in replacement of missing teeth in either jaw.

Materials And Methods: Twenty hybrid implants were placed in maxilla and mandible and the implants were assessed for pain,implant exposure, mobility, infection and wound dehiscence at first, third and sixth month postoperatively.

Results: According to our study the statistical data showed that all the parameters which were seen clinically were nonsignificant.

Conclusion: Hybrid implants being a new option in this field, our study provides a platform for further research with larger sample size with longer follow ups to be judgemental on their efficacy.
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http://dx.doi.org/10.4103/njms.NJMS_61_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883870PMC
November 2019

XRCC1 632 as a candidate for cancer predisposition via a complex interaction with genetic variants of base excision repair and double strand break repair genes.

Future Oncol 2019 Nov 11;15(33):3845-3859. Epub 2019 Nov 11.

Department of Biotechnology, Thapar University, Patiala, Punjab 147002, India.

The DNA repair system safeguards integrity of DNA. Genetic alterations force the improper repair which in conjugation with other factors ultimately results in carcinogenesis. PCR-restriction fragment length polymorphism was used for genotyping, which was followed by statistical analysis using logistic regression analysis, multifactor dimensionality reduction and classification and regression analysis tree, elaborating the association with lung cancer subjects. Combination of and showcased a high risk of eightfold (odds ratio: 7.92; 95% CI: 2.68-23.4; p = 0.0002; false discovery rate (FDR) p = 0.002). Similarly, and (odds ratio: 5.07; 95% CI: 2.6-9.67; p < 0.0001; FDRp = 0.002) had a high risk. Multifactor dimensionality reduction analysis revealed five factor model as the best model with prediction error of 0.37 (p = 0.02). There was a clear indication that high order interactions were major role players in the study.
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http://dx.doi.org/10.2217/fon-2019-0297DOI Listing
November 2019

Filariasis presenting as a solitary testicular mass.

Trop Parasitol 2019 Jul-Dec;9(2):124-126. Epub 2019 Sep 18.

Department of Pathology, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, Uttarakhand, India.

In an endemic country like India, the occurrence of filariasis is very common, especially in the states of Uttar Pradesh, Bihar, Jharkhand, Odisha, Andhra Pradesh, and Tamil Nadu. The present study describes the case of a male from a nonendemic state who presented with a testicular lump. Fine-needle aspiration cytology (FNAC) of the lump revealed many adult filarial worms. The appearance of adult filarial worms in different sites, other than lymph nodes and lymphatic vessels, are relatively rarer and should always be reported. Filariasis remains asymptomatic for a long time and responds very well to treatment if diagnosed early. Despite the availability of multiple diagnostic options, FNAC holds a great importance in diagnosing filariasis, especially in cases where there are normal eosinophil counts and no peripheral filarial parasite. Finally, careful examination of cytological smear for the parasite in high-risk groups is helpful in labeling the disease in early asymptomatic states.
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http://dx.doi.org/10.4103/tp.TP_15_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767791PMC
September 2019

Catalyst- and Solvent-Free Coupling of 2-Methyl Quinazolinones and Isatins: An Environmentally Benign Access of Diastereoselective Schizocommunin Analogues.

ACS Omega 2019 Jul 15;4(7):12146-12155. Epub 2019 Jul 15.

Department of Chemistry, Mohanlal Sukhadia University, Udaipur 313001, India.

An environmentally benign highly atom-economic protocol for the construction of the C-C bond has been developed under catalyst- and solvent-free conditions. This protocol involves the efficient coupling of 2-methyl quinazolinones with isatin for the highly diastereoselective access of schizocommunin derivatives in excellent yields (up to 97%). Furthermore, the preliminary cytotoxicity screening of selected schizocommunin analogues displayed promising anticancer activity against human cancer cell lines, and the cytotoxic potential of active compound was also validated by in silico molecular docking simulation studies.
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http://dx.doi.org/10.1021/acsomega.9b01514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682076PMC
July 2019

Phenanthridine-Fused Tetracyclic Ring System: Metal-Free Diastereoselective Modular Construction of Highly Constrained Polyheterocycles via Post-Ugi Tandem Modifications.

Org Lett 2019 09 15;21(17):6726-6730. Epub 2019 Aug 15.

Department of Chemistry, Mohanlal Sukhadia University, Udaipur 313001, India.

A metal-free diastereo-/regioselective modular synthetic approach for the synthesis of highly constrained tetrahydroquinoline-fused tetracyclic heterocycles from easily available substrates has been developed. This two-step strategy utilizes an Ugi four-component reaction, followed by the intramolecular spirocarbocyclization and iodination reactions in a single operation. The transformation is mild and operationally simple, which provides architecturally complex polycyclic heterocycles with high diastereoselectivity. Furthermore, the preliminary cytotoxicity screening of selected compounds displayed promising anticancer activity against human cancer cell lines.
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http://dx.doi.org/10.1021/acs.orglett.9b02340DOI Listing
September 2019

The multi-faceted high order polymorphic synergistic interactions among nucleotide excision repair genes increase the risk of lung cancer in North Indians.

Mutat Res 2019 11 8;816-818:111673. Epub 2019 Jun 8.

Department of Pulmonary Medicine, Post Graduate Institute of Medical Education & Research (PGIMER), Sector 14, Chandigarh, India.

It is evident that gene-gene interactions are pervasive in the determination of the susceptibility of human diseases. Polymorphisms in nucleotide excision repair pathway (NER) genes can cause variations in the repair capacity and therefore, might lead to increase in susceptibility towards lung cancer through complex gene-gene and gene-smoking interactions. Logistic regression analysis, along with high order genetic interaction were analyzed using data mining tools such as multifactor dimensionality reduction (MDR) and classification and regression tree analysis (CART). Overall, a protective effect was reported when a combinatorial effect of SNPs were studied by applying logistic regression analysis. Multifactor dimensionality reduction (MDR) analysis, revealed that the four factor model i.e. XPC K939Q, XPA 5'UTR, XPG F670W and XPG D1104H had the best ability to predict lung cancer risk (CVC = 100, p < 0.0001). While a two factor model, including smoking and XPG F670W suggested smoking was associated with the risk of developing lung cancer (CVC = 100, p < 0.0001). Individually XPG F670W was identified as the primary risk factor. In classification and regression tree analysis (CART), we observed a 6-fold risk for SCLC patients carrying XPA 5'UTR (M), XPD K751Q (W) (OR: 6.20; 95%CI: 2.40-16.01, p = 0.0001).Polymorphic NER genes might jointly modulate lung cancer risk through gene-gene and gene-smoking interaction.
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http://dx.doi.org/10.1016/j.mrfmmm.2019.111673DOI Listing
November 2019

Selenium-rich maize modulates the expression of prostaglandin genes in lipopolysaccharide-stimulated RAW264.7 macrophages.

Food Funct 2019 May;10(5):2839-2846

Thapar Institute of Engineering and Technology, Patiala, India.

Cell signaling is necessary for the organs to co-ordinate with the whole body and it includes response to external stimuli, inflammation, hormonal secretions and other various metabolic functions. In the present study, we have focused on the inflammatory signals modulated by the reactive oxygen and nitrogen species (RONS). Under homeostatic conditions, these species turn on the COX-1-dependent arachidonic acid (AA) pathway towards the release of anti-inflammatory enzymes. However, the excess release of these ions induces negative effects in the form of inflammation by turning on the COX-2-dependent AA pathway to release pro-inflammatory enzymes. In the present study, we observed the shunting of the COX-2-dependent AA pathway towards the release of anti-inflammatory enzymes with the supplementation of organic dietary selenium in the form of seleniferous maize extracts. We observed that 500 nM selenium concentration in Se-maize extracts downregulated the COX-2 and mPGES-1 expressions by 3.8- and 3.2-fold and upregulated the GPx-1 and H-PGDS expressions by 5.0- and 5.4-fold, respectively. To facilitate more availability of Se from the dietary matrices, Se-maize extracts were incubated with rMETase. It was observed that the enzyme-treated cells increased the downregulation of COX-2 and mPGES-1 expressions by 24.8- and 21.0-fold and the upregulation of GPx-1 and H-PGDS expressions by 13.2- and 16.5-fold, respectively.
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http://dx.doi.org/10.1039/c9fo00186gDOI Listing
May 2019

Current scenario of artemisinin and its analogues for antimalarial activity.

Eur J Med Chem 2019 Feb 13;163:804-829. Epub 2018 Dec 13.

Department of Chemistry, Banasthali University, Banasthali Newai, 304022, Rajasthan, India. Electronic address:

Human malaria, one of the most striking, reemerging infectious diseases, is caused by several types of Plasmodium parasites. Whilst advances have been made in lowering the numbers of cases and deaths, it is clear that a strategy based solely on disease control year on year, without reducing transmission and ultimately eradicating the parasite, is unsustainable. Natural products have served as a template for the design and development of antimalarial drugs currently in the clinic or in the development phase. Artemisinin combine potent, rapid antimalarial activity with a wide therapeutic index and an absence of clinically important resistance. The alkylating ability of artemisinin and its semi-synthetic analogues toward heme related to their antimalarial efficacy are underlined. Although impressive results have already been achieved in malaria research, more systematization and concentration of efforts are required if real breakthroughs are to be made. This review will concisely cover the clinical, preclinical antimalarial and current updates in artemisinin based antimalarial drugs. Diverse classes of semi-synthetic analogs of artemisinin reported in the last decade have also been extensively studied. The experience gained in this respect is discussed.
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http://dx.doi.org/10.1016/j.ejmech.2018.12.007DOI Listing
February 2019

XPG polymorphisms and their association with lung cancer susceptibility, overall survival and response in North Indian patients treated with platinum-based doublet chemotherapy.

Future Oncol 2019 Jan 7;15(2):151-165. Epub 2018 Dec 7.

Department of Biotechnology, Thapar University, Punjab 147002, India.

Aim: The study investigates association of XPG polymorphism with lung cancer susceptibility, overall survival and clinical outcomes in North Indian population.

Results: A significant protective effect was observed for 2228959 C/A polymorphism with lung cancer and its histological subtypes. An increased hazard ratio (HR) was observed in 17655 G/C variant among small-cell lung carcinoma patients with mutant genotype (HR: 2.55; p = 0.05). Individuals treated with irinotecan-cisplatin/carboplatin regimen showed a longer survival time (HR: 0.04; median survival time [MST]: 32.5 months). Subjects treated with pemetrexed-cisplatin/carboplain regimen were associated with higher mortality rate in lung cancer patients (HR: 1.83;  MST: 9.13 months).

Conclusion: 2228959 C/A polymorphism contributes to protective effect in lung cancer patients. 2228959 C/A polymorphism might be associated with favorable prognosis in lung cancer risk.
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http://dx.doi.org/10.2217/fon-2018-0408DOI Listing
January 2019

Genetic Variants in the Wingless Antagonist Genes (, , and ) Predict the Overall Survival and Prognosis of North Indian Lung Cancer Patients Treated with Platinum-Based Doublet Chemotherapy.

Cancer Biother Radiopharm 2018 Dec 20;33(10):466-477. Epub 2018 Oct 20.

Department of Biotechnology, Thapar University, Patiala, India.

To investigate the prognostic implication of genetic variants within the wingless (Wnt) antagonist genes (, , and ) in North Indian lung cancer patients. A total of 212 subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism technique for 18 polymorphic sites in , , , , , and . Overall survival (OS) was estimated using the Kaplan-Meier survival analysis, and adjusted hazard ratio (HR) was obtained using the Cox regression method. It was observed that the unfavorable genotypes of the three variants collectively (rs447372, rs419558, and rs17037102) exhibited a highly decreased rate of death (adjusted HR = 0.37,  = 0.03). Adenocarcinoma (ADCC) patients carrying the heterozygous (CT) genotype for rs2073664 showed a better OS compared with wild genotype (log rank  = 0.01). The two exonic variants ( and ) of gene showed contrasting results, where the ADCC subjects having TT genotype for showed a better prognosis (adjusted HR = 0.48,  = 0.003) and those with TT genotype for showed a poor prognosis in small-cell lung carcinoma patients (adjusted HR = 2.33,  = 0.02). The intronic variant on the other hand indicated a highly increased death risk in ADCC patients with GG genotype. Survival tree analysis depicted DKK4 rs2073664 as the major contributor in predicting the survival of the lung cancer patients. Node 3 exhibited the lowest death rate (HR = 0.04,  = 0.008) and better median survival time (9 months vs. 3 months) when compared with reference node. A cumulative effect of three variants of gene along with rs2073664 can jointly predict the survival as shown by tree analysis.
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http://dx.doi.org/10.1089/cbr.2018.2491DOI Listing
December 2018

Supporting Resident Research Learning in the Workplace: A Rapid Realist Review.

Acad Med 2018 11;93(11):1732-1740

C. Noble is principal medical education officer and principal research fellow (Allied Health), Gold Coast Health, senior lecturer, School of Medicine, Griffith University, senior lecturer, School of Pharmacy, University of Queensland, Queensland, Australia; ORCID: https://orcid.org/0000-0001-8763-234X. S.R. Billett is professor, Professional, Continuing, and Vocational Education, Griffith University, Queensland, Australia; ORCID: https://orcid.org/0000-0002-9926-3518. D.T.Y. Phang is intern medical officer, Gold Coast Health, and associate lecturer, School of Medicine, Griffith University, Queensland, Australia; ORCID: https://orcid.org/0000-0003-4414-2695. S. Sharma is acting director, Internal Medicine, Gold Coast Health, network training coordinator, Queensland Physician Training Network, and senior lecturer, School of Medicine, Griffith University, Queensland, Australia; ORCID: https://orcid.org/0000-0002-4975-7309. F. Hashem is staff specialist, Endocrinology, Gold Coast Health, and senior lecturer, School of Medicine, Griffith University, Queensland, Australia; ORCID: https://orcid.org/0000-0002-9870-422X. G.D. Rogers is professor of medical education, deputy head, Learning & Teaching, School of Medicine, and program lead, Interprofessional and Simulation-Based Learning, Health Institute for the Development of Education and Scholarship, Griffith University, Queensland, Australia; ORCID: https://orcid.org/0000-0003-4655-0131.

Purpose: Residents are increasingly expected to engage in practice-based research; however, engagement in research whilst also fulfilling clinical duties is often challenging. Evidence suggests that residents require specific developmental experiences, along with clinical practice, to become effective researchers. The authors therefore conducted a rapid realist review to explore strategies and key mechanisms supporting effective resident research activities in clinical settings. They examined relationships amongst different clinical contexts, learning mechanisms, and research engagement outcomes to provide evidence-based, theory-informed recommendations for improving resident research engagement and extending understandings of workplace learning in health care settings.

Method: In 2015-2016, the authors used a rapid realist methodology informed by workplace learning theory to review international literature published between January 2005 and December 2015. The review drew upon sources from OVID Medline, ERIC, Embase, and AustHealth. The authors screened articles for eligibility using inclusion criteria and appraised articles using realist review quality criteria.

Results: The authors included 51 articles in the review. The review process identified three key mechanisms for effective integration and support of resident research engagement, as informed by workplace learning theory: (1) opportunities to engage in practice-informed research supported by longitudinal curricula, (2) guidance by clinician-researchers, and (3) assessing residents' research readiness and promoting their intentionality for engagement.

Conclusions: This review extends existing literature and informs workplace-based research engagement strategies for residents whilst demonstrating the applicability of workplace learning theory to improving residents' research engagement. The authors propose a learning model to support effective resident research engagement through clinical practice.
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http://dx.doi.org/10.1097/ACM.0000000000002416DOI Listing
November 2018

Functional role of CyclinD1 polymorphism (G870A) in modifying susceptibility and overall survival of North Indian lung cancer patients.

Tumori 2018 Jun;104(3):179-187

2 Department of Pulmonary Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh - India.

Purpose: The purpose of this study was to investigate the potential role of the cyclin D1 gene G870A polymorphism in the likelihood of the development of lung cancer and the overall survival of lung cancer patients in the North Indian population.

Methods: The study consisted of 353 lung cancer cases and 351 age- and gender-matched healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLPP) was done for the CCND1 gene. The association analysis was done using the multiple linear regression, and the survival analysis was done using the Kaplan-Meier and the Cox regression models.

Results: The GA genotype was associated with an increased risk for overall lung cancer (odds ratio [OR] = 1.63; p = 0.01). Combined variant genotype showed a significant association for overall lung cancer (OR 1.50; p = 0.03). In addition, smokers with the carrier genotype of CCND1 were found to have a significantly higher risk for lung cancer (OR 1.57; p = 0.04). No significant correlation was observed between the overall survival of lung cancer patients and CCND1 polymorphism. However, on stratifying the subjects on the basis of histology, it was evident that small-cell lung cancer (SCLC) patients carrying the mutant (AA) genotype showed nearly a fivefold increased mortality rate compared to the wild (GG) genotype (p = 0.03).

Conclusions: Our results suggest that polymorphic CCND1 may increase the risk of lung cancer in smokers from North India, and it may be associated with the overall survival of SCLC patients.
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http://dx.doi.org/10.1177/0300891617753477DOI Listing
June 2018
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