Unravelling the Significance of NLRP3 and IL-ß1 in Oral Squamous Cell Carcinoma and Potentially Malignant Oral Disorders: A Diagnostic and Prognostic Exploration.

BACKGROUND: Nucleotide-binding domain-like receptor protein 3 (NLRP3), an inflammasome, is reported to be dysregulated or aberrantly expressed in chronic inflammation, leading to a myriad of inflammatory disorders, autoimmune diseases, and cancer. This study aimed to explore the expression and role of NLRP3 protein and the secreted cytokine IL-ß1 in oral squamous cell carcinoma (OSCC) and potentially malignant oral disorders (PMOD). MATERIAL & METHODS: Tissue NLRP3 expression was quantified using sandwich ELISA in 30 cases each of OSCC, PMOD, and normal oral mucosa. Serum IL-ß1 level was also measured by ELISA to determine their correlation. In surgically treated OSCC cases, pathological parameters such as tumor size, depth of invasion (DOI), pTNM stage, and perineural & lymphovascular invasion were assessed and correlated with NLRP3 & IL-ß1 levels to investigate their roles in tumor progression, invasion, and metastasis. RESULTS: Tissue NLRP3 expression was markedly elevated in OSCC, with significant IL-ß1 levels observed in the serum of both OSCC and PMOD cases. Both markers showed a pronounced increase with the severity of dysplasia, indicating a strong association (p = 0.003%). The expression levels of tissue NLRP3 and serum IL-ß1 were positively correlated with DOI and tumor size. Furthermore, their elevated levels, alongside higher histological grades, indicate roles in the dedifferentiation and progression of tumor cells. CONCLUSION: The findings indicated that increased expression of NLRP3 and IL-ß1 in PMOD correlates with higher transformation rates, along with tumor progression and dedifferentiation in OSCC. Consequently, these markers hold promise as valuable targets for prognostic assessment, diagnostics, and therapeutic strategies in OSCC.

Analysis of the gamma index using an indigenously developed anthropomorphic heterogeneous female pelvis (AHFP) phantom.

BACKGROUND: It is essential in modern radiotherapy treatment practices to evaluate the quality assurance (QA) of the treatment plan prior to the exclusion of patient from treatment. The typical suitable tools used for patient pretreatment QA are phantoms representing the human anatomy. An anthropomorphic heterogeneous female pelvic (AHFP) phantom has been developed to represent the real female pelvic structure. PURPOSE: The objective of the current study is to assess the findings of relative dosimetry carried out utilizing an electronic portal imaging device (EPID) on the AHFP phantom fabricated. METHODS: The planning target volume (PTV) was created on CT slices of an AHFP phantom to confirm the tool's ability to represent female pelvic anatomy and serve as a QA tool. In order to assess the dose received by healthy organs during radiotherapy, organs at risk such as the bladder and rectum were additionally drawn alongside the PTV. Rapid Arc and Intensity modulated radiation therapy (IMRT) were both used to create the treatment plan on treatment planning system, and the Anisotropic Analytical Algorithm Version 11.0.31 was used to calculate the dose. RESULTS: The results obtained for the average gamma value in RapidArc plans are 0.26, 0.27, and 0.28 (g ≤1) and IMRT plans are 0.39, 0.40, and 0.46 (g ≤1) for target 1, target 2, and target 3, respectively. CONCLUSION: According to the findings of the current study, the AHFP phantom was used to explore the potential of relative dosimetry using EPID as a QA tool, which was found to be suitable.

Comparative evaluation of mucin and total protein in periodontal disease before and after nonsurgical periodontal therapy.

Background: Periodontal ailments cause a quantum leap in the biomarker profile of the saliva. This profile is, in fact, the epiphany of the scale and extent of the disease. Both gingivitis and periodontitis are chronic inflammatory diseases with a step-grade progression. The study aimed to determine the response of the host in these conditions by analyzing concentrations of salivary mucin and total protein activity, before and after nonsurgical periodontal therapy (NSPT). Materials and Methods: Sixty adult subjects were clinically examined and divided into three groups (n = 20) according to the clinical assessment and categorized as Group I (healthy), Group II (gingivitis), and Group III (chronic periodontitis). Whole saliva was collected, and salivary mucin and total protein levels were quantitatively measured at baseline in all the groups and additionally after NSPT in Groups II and III. Results: Levels of mucin and total protein increased in patients with gingivitis and periodontitis. There was a slight decline in mucin levels in periodontitis patients in comparison with the gingivitis group. A positive correlation was found between the respective clinical parameters of both the groups along with their levels of salivary mucin and total protein. It indicated that the response of salivary glands to increase their protective potential caused the change among the groups. Conclusion: Periodontal diseases induce an increase in the levels of mucins and proteins, which is believed as the action of the salivary glands to protect the oral cavity and put off the chaos caused by the microorganisms.

Evaluation of canal patency and cleanliness following retreatment of bioceramic sealer-obturated root canals using three different irrigant activation protocols.

This study evaluated the effectiveness of three different irrigant activation techniques in cleaning and establishing patency during retreatment of root canals obturated with gutta-percha and bioceramic sealer. 60 extracted premolars with oval-shaped canals were instrumented and obturated with gutta-percha and EndosequenceBC sealer using the 'warm hydraulic condensation' technique. The teeth were retreated using Protaper Universal Retreatment and XP-Endo Shaper system and divided into four groups according to the irrigant activation protocol used: control, passive ultrasonic irrigation (PUI), Endovac irrigation (EVI) and XP-Endo Finisher R (XPFR). Apical patency was achieved in all the samples of the XPFR group (100%), which showed a significantly higher success rate compared with the control (73.3%) and EVI groups (73.3%) (p < 0.05). The scanning electron microscopic evaluation revealed significantly cleaner middle and apical third root canals in the PUI and XPFR groups compared with the control group (p < 0.05). These findings suggest that XPFR effectively cleans and establishes patency in root canals filled with bioceramic sealers.

Efficacy of the collapsed cone algorithm calculated radiotherapy plans in intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT): A comparative dosimetric study in tumors of thorax.

AIM: In this study, efficacy of collapsed cone algorithm-generated intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) were evaluated for treatment of thoracic esophageal cancer. MATERIALS AND METHODS: Ten previously treated patients with VMAT were considered for evaluation. The planning parameters were evaluated in terms of max dose, mean dose, Homogeneity Index, Conformity Index for planning target volume, and organ at risk doses. Total monitor unit, treatment time, and gamma passing index were also reported. RESULTS: The target dose coverage of the VMAT and IMRT plans achieved the clinical dosimetric criteria for all ten patients in the evaluation. Under the condition of equivalent target dose distribution, the VMAT plan's Conformity Index, monitor unit, treatment time, and gamma passing index rate were superior than in the IMRT plan, and the result was statistically significant. CONCLUSION: Collapsed cone algorithm-based VMAT can have a more effective and better approach for esophageal cancer than IMRT.

Comparative evaluation of digital radiography, electronic apex locator and simultaneous working length determination on postoperative pain after root canal treatment: a randomized clinical trial.

Purpose: The study aimed to compare postoperative pain after root canal preparation using three different methods of working length determination. Materials and methods: 60 patients diagnosed with symptomatic irreversible pulpitis were randomly divided into three groups based on the method of working length (WL) determination. Group 1: digital radiograph (DRG), Group 2: electronic apex locator (EAL), Group 3: the simultaneous working length control (SLC) method using an endomotor with an integrated apex locator. The root canal treatments were completed in a single visit, and patients were asked to record their pain response using the Visual Analog Scale (VAS) at 6, 24, 48, and 72 hours postoperatively. Results: Group 1 (DRG) recorded the highest postoperative pain score, while the lowest was recorded by Group 3 (SLC). There was a statistically significant difference in the VAS pain scores between DRG and SLC (p<0.05) at 6-, 24- and 48-hour intervals. Conclusion: Within the limitations of this study, it can be concluded that the SLC can be a helpful working length determination technique to reduce postoperative pain.

Evaluation of Radiation Treatment Planning Algorithms in IMRT and VMAT: A Comparative Dosimetric Study in Lung Equivalent Heterogeneous Medium.

Background: In Radiotherapy, computation of dose is important since in a small field with heterogeneity, dose is usually computed with discrepancies. Objective: The present study was aimed to evaluate the dosimetry of treatment planning algorithms in lung equivalent heterogeneous medium for Volumetric Modulated Arc Therapy (VMAT) with step and shoot Intensity-Modulated Radiation Therapy (ss-IMRT), and dynamic Intensity-Modulated Radiation Therapy (d-IMRT). Material and Methods: In this experimental study, Computerized Imaging Reference System (CIRS) phantom was used with an inhomogeneous Racemosa wood cylinder for two types of tumors, namely, Left Lung Central Tumor (LCT) and Left Lung Peripheral Tumor (LPT) in the CIRS left lung cavity. The computed tomography (CT) datasets were employed with the generation of VMAT, d-IMRT and ss-IMRT plans for the LCT and LPT irradiated with 6 MV photon beams. In this study, the accuracy and efficacy of two algorithms: Monte Carlo (MC) and the Pencil Beam (PB), from the Monaco treatment planning system (TPS), were tested by using Gafchromic EBT3 films and CIRS thorax phantom. Results: Regardless of treatment techniques, both algorithms exhibited higher divergence in LPT than LCT. In both LCT and LPT, the highest deviation was near the tumor-lung junction. However, the deviation was higher in the PB algorithm than MC algorithm, with a minimally acceptable variation of -0.8%. Conclusion: The MC algorithm shows more consistency for EBT3 measured dose in lung equivalent heterogeneous medium. However, accurate dose predictions are complicated due to electronic disequilibrium within and at the interface of inhomogeneity. These constraints may cause variations from the anticipated outcomes of the treatments.

Combination of image-guided IMRT and IGBT in locally advanced carcinoma cervix: Prospective evaluation of toxicities and clinical outcomes from a tertiary cancer center in India.

Purpose: We aimed to assess the toxicity profile and clinical outcome in patients with locally advanced cervical cancer (LACC) treated with a combination of image-guided intensity-modulated radiation therapy (IG-IMRT) and image-guided brachytherapy (IGBT). Material and methods: 25 LACC patients were recruited in this single-arm prospective study. Whole pelvis IG-IMRT was delivered (45 Gy with simultaneously integrated nodal boost of 55 Gy in 25 fractions), with concurrent weekly cisplatin (40 mg/m2). Patients received IGBT of 7 Gy each in 4 fractions to high-risk clinical target volume (HR-CTV). First fraction was done under MRI, and subsequent fractions were performed under CT guidance. Primary endpoint was acute toxicity, and secondary endpoints were 2-year loco-regional control and late toxicity. Results: The median age was 52 years, and FIGO 2018 stage distribution was IIA2, IIB, IIIB, and IIIC1 in 12%, 40%, 20%, and 28% patients, respectively. All patients received concurrent chemotherapy with median number of 5 cycles (range, 4-5 cycles). Grade 1 and 2 diarrhea, and grade 1 cystitis was reported in 4 (16%), 3 (12%), and 2 (8%) patients, respectively. Grade 1 and 2 anemia, and grade 1 and 2 dermatitis were observed in 3 (12%) and 2 (8%), and 3 (12%) and 3 (12%) patients, respectively. No patient reported grade 3-4 acute toxicity. At median follow-up of 29.5 months (range, 25-37 months), late grade 1 bladder toxicity was observed in 1 (4%) patient. Loco-regional control at 1 and 2 years were 96% and 92%, respectively. Conclusions: The combination of IG-IMRT and IGBT yielded excellent outcomes in terms of acute toxicity and loco-regional control.

Dosimetric Comparision of Coplanar versus Noncoplanar Volumetric Modulated Arc Therapy for Treatment of Bilateral Breast Cancers.

Introduction: The purpose of this study was to compare the dosimetric parameters of volumetric modulated arc therapy (VMAT) treatment plans using coplanar and noncoplanar beams in patients with bilateral breast cancer/s (BBCs) in terms of organ at risk sparing and target volume coverage. The hypothesis was to test whether VMAT with noncoplanar beams can result in lesser dose delivery to critical organs such as heart and lung, which will result in lesser overall toxicity. Materials and Methods: Data of nine BBC cases treated at our hospital were retrieved. Computed tomography simulation data of these cases was used to generate noncoplanar VMAT plans and the parameters were compared with standard VMAT coplanar plans. Contouring was done using radiation therapy oncology group guidelines. Forty-five Gray in 25 fractions was planned followed by 10 Gy in five fractions boost in breast conservation cases. Results: No significant difference in planning target volume (PTV) coverage was found for the right breast/chestwall (P = 0.940), left breast/chestwall (P = 0.872), and in the total PTV (P = 0.929). Noncoplanar beams resulted in better cardiac sparing in terms of Dmean heart. The difference in mean dose was >1 Gy (8.80 ± 0.28 - 7.28 ± 0.33, P < 0.001). The Dmean, V20 and V30 values for total lung slightly favor noncoplanar beams, although there was no statistically significant difference. The average monitor units (MUs) were similar for coplanar plans (1515 MU) and noncoplanar plans (1455 MU), but the overall treatment time was higher in noncoplanar plans due to more complex setup and beam arrangement. For noncoplanar VMAT plans, the mean conformity index was slightly better although the homogeneity indices were similar. Conclusion: VMAT plans with noncoplanar beam arrangements had significant dosimetric advantages in terms of sparing of critical organs, that is Dmean of heart doses with almost equivalent lung doses and equally good target coverage. Larger studies with clinical implications need to be considered to validate this data.

Toxicities and clinical outcome of adjuvant dysphagia optimized versus standard intensity-modulated radiotherapy for post-operative oral cavity cancers: A prospective comparative study.

BACKGROUND: We prospectively assessed acute and late toxicity in post-operative oral cavity squamous cell carcinoma (PO-OCSCC) treated with adjuvant dysphagia optimized intensity-modulated radiotherapy (Do-IMRT) versus standard IMRT (S-IMRT). MATERIAL AND METHODS: Fifty-six patients of PO-SCC without indications of concurrent chemotherapy were alternatively allocated to adjuvant Do-IMRT (n = 28) versus S-IMRT (n = 28) arms. High- and low-risk planning target volume received 60 and 54 Gy, respectively, in 30 fractions over 6 weeks. Dysphagia aspiration-related structures (DARS) were contoured in both arms. While dosimetric constraints were given in Do-IMRT arm, doses to DARS were only observed without dose constraints in S-IMRT arm. Acute and late toxicity were assessed by common terminology criteria for adverse events (CTCAE) v5.0 and RTOG criteria, respectively. RESULTS: The primary site of disease was buccal mucosa (64% vs. 53%) and oral tongue (21% vs. 32%), in Do-IMRT and S-IMRT, respectively. The mean doses to DARS was significantly less with Do-IMRT (all p < 0.001) as compared to S-IMRT. Median follow-up was 24.2 months. Grade ≥2 oral pain was less in the Do-IMRT arm (50% vs. 78.6%, p = 0.05). Grade ≥2 late dysphagia at 2 years were significantly less in Do-IMRT arm (0% vs. 17.9%, p = 0.016). Two-year locoregional control was 89.2% in Do-IMRT and 78.5% in S-IMRT (p = 0.261). CONCLUSION: DARS can be spared in PO-OCSCC patients treated with Do-IMRT without compromising coverage of the target volumes. Limiting doses to DARS leads to lesser acute and late toxicity without compromising locoregional control.

Development of an Anthropomorphic Heterogeneous Female Pelvic Phantom and Its Comparison with a Homogeneous Phantom in Advance Radiation Therapy: Dosimetry Analysis.

BACKGROUND: Accurate dosimetry is crucial in radiotherapy to ensure optimal radiation dose delivery to the tumor while sparing healthy tissues. Traditional dosimetry techniques using homogeneous phantoms may not accurately represent the complex anatomical variations in cervical cancer patients, highlighting the need to compare dosimetry results obtained from different phantom models. PURPOSE: The aim of this study is to design and evaluate an anthropomorphic heterogeneous female pelvic (AHFP) phantom for radiotherapy quality assurance in cervical cancer treatment. MATERIALS AND METHOD: Thirty RapidArc plans designed for cervical cancer patients were exported to both the RW3 homogeneous phantom and the anthropomorphic heterogeneous pelvic phantom. Dose calculations were performed using the anisotropic analytic algorithm (AAA), and the plans were delivered using a linear accelerator (LA). Dose measurements were obtained using a 0.6 cc ion chamber. The percentage (%) variation between planned and measured doses was calculated and analyzed. Additionally, relative dosimetry was performed for various target locations using RapidArc and IMRT treatment techniques. The AHFP phantom demonstrated excellent agreement between measured and expected dose distributions, making it a reliable quality assurance tool in radiotherapy. RESULTS: The results reveal that the percentage variation between planned and measured doses for all RapidArc quality assurance (QA) plans using the AHFP phantom is 10.67% (maximum value), 2.31% (minimum value), and 6.89% (average value), with a standard deviation (SD) of 2.565 (t = 3.21604, p = 0.001063). Also, for the percentage of variation between homogeneous and AHFP phantoms, the t-value is -11.17016 and the p-value is <0.00001. The result is thus significant at p < 0.05. We can see that the outcomes differ significantly due to the influence of heterogeneous media. Also, the average gamma values in RapidArc plans are 0.29, 0.32, and 0.35 (g ≤ 1) and IMRT plans are 0.45, 0.44, and 0.42 (g ≤ 1) for targets 1, 2, and 3, respectively. CONCLUSION: The AHFP phantom results show more dose variability than homogenous phantom outcomes. Also, the AHFP phantom was found to be suitable for QA evaluation.

Prospective evaluation of dose-escalated preoperative concurrent chemo-radiation with image guided-IMRT in locally advanced rectal cancers.

Purpose: To analyse the safety and efficacy of neoadjuvant chemoradiation (NACRT) with dose-escalated image-guided intensity modulated radiation therapy (IG-IMRT) in locally advanced (T3/4; T1-4N1-2) rectal cancers (LARCs). Materials and methods: Twenty patients with the diagnosis of LARC were recruited in this prospective interventional single-arm study treated by IG-IMRT with 45 Gray (Gy) in 25 fractions to elective nodal volumes and 55 Gy in 25 fractions to the gross primary and nodal disease with concurrent capecitabine 825 mg/m2 twice daily on radiotherapy days. Patients underwent total mesorectal excision 6-8 weeks post completion of NACRT followed by adjuvant chemotherapy (Capecitabine and oxaliplatin every 3 weekly for 6-8 cycles). Primary end point was acute toxicity assessment and secondary end points were pathological complete response (pCR) and loco-regional control (LRC). Results: Clinical T stage was T3:T4 in 19:1 and clinical N0:N1: N2 in 2:7:11 patients, respectively. With a median follow up of 21.2 months (13.8-25.6 months), 18 of 20 (90%) patients received the full course of treatment. Tumour and nodal downstaging was achieved in 78% and 84% of patients, respectively. pCR and overall complete response (defined as pCR and near CR) was achieved in 22.2% and 44.4% of patients, respectively. 2 (10%) patients completed NACRT, and achieved complete clinical response but refused surgery. Adjuvant chemotherapy course was completed by 17/18 (94.5%) patients. Grade 3 toxicities were observed in 2 (10%) patients during NACRT. All patients were disease-free at the time of the last follow up. Conclusion: Dose-escalation of NACRT therapy with IG-IMRT in LARC patients offers decent rates of pCR and overall response with excellent LRC and acceptable toxicities.

Prevalence of Hyperglycemia in Pregnancy and Related Screening Practices in Rural Dehradun: The First Population-Based Study from Uttarakhand (PGDRD-1).

Aims: Phase I of the Prevalence of Gestational Diabetes Mellitus in Rural Dehradun (PGDRD) project estimates hyperglycemia in pregnancy (HIP) prevalence and identifies gaps in the utilization of community-related services in rural areas of the Dehradun district (western Uttarakhand); a state where notably no prior population-based study has ever been conducted despite being an Empowered Action Group state for more than two decades. Methods: Using a multistage random sampling technique, 1,223 pregnant women locally registered in the rural field practice area of a block were identified. Those requiring HIP screening were subjected to a 2-h 75 g oral glucose tolerance test during the house visit irrespective of their period-of-gestation and last meal timings, diagnosed using the Diabetes in Pregnancy Study Group India (DIPSI) criterion (when indicated). Data were collected by personal interviews using a pretested data collection tool. Statistical Package for Social Sciences version 20.0 was used for analysis. Results: The overall HIP prevalence recorded was 9.7% (95% CI: 8.1-11.5%); the majority (95.8%) were GDM followed by overt DIP (4.2%). Less than 1% of the subjects (0.7%) self-reported pre-GDM. Despite this burden, more than three-fourths were never screened for HIP in their pregnancy. Of those tested, the majority availed secondary healthcare facilities. Few even had to bear expenses in private with a very handful being tested free-of-cost by ANM in the community; findings that altogether sharply contrast to those recommended by national protocols. Conclusion: Despite the high HIP burden, beneficiaries are unable to utilize community-related universal screening protocols as desired.

Characterization and assessment of hydrological droughts using GloFAS streamflow data for the Narmada River Basin, India.

Hydrological droughts severely affect the demand of water for domestic water supply, irrigation, hydropower generation, and several other purposes. The pervasiveness and consequences of hydrological droughts necessitate a thorough investigation of their characteristics, which is hindered due to unavailability of continuous streamflow records at desirable resolutions. This study aims to assess the hydrological drought characteristics and their spatial distribution using high-resolution Global Flood Awareness System (GloFAS) v3.1 streamflow data for the period 1980 to 2020. Streamflow Drought Index (SDI) was used to characterize droughts at 3-, 6-, 9-, and 12-monthly timescales starting from June, i.e., the start of water year in India. GloFAS is found to capture the spatial distribution of streamflow and its seasonal characteristics. The number of hydrological drought years over the basin varied from 5 to 11 during the study duration, implying that the basin is prone to frequent abnormal water deficits. Interestingly, the hydrological droughts are more frequent in the eastern portion of the basin, i.e., the Upper Narmada Basin. The trend analysis of multi-scalar SDI series using non-parametric Spearman's Rho test exhibited increasing drying trends in the easternmost portions. The results were not similar for the middle and western portions of the basin, which may be due to presence of a large number of reservoirs in these regions and their systematic operations. This study highlights the importance of open-access global products that can be used for monitoring hydrological droughts, especially over ungauged catchments.

Long term outcome and late toxicity Of SIB-IMRT in definitive management of head and neck cancers in patients not suitable for chemo-radiotherapy.

Objective: To evaluate efficacy and late toxicity of intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) in definitive management of head-and-neck cancers. Methods: In this prospective interventional study, histological proven squamous cell carcinoma of oropharynx, hypopharynx, or larynx with stage T1-3 N0-3 M0 who were not candidates for concurrent chemotherapy were treated with IMRT-SIB with radical intent. Doses prescribed for IMRT-SIB to meet the clinical needs of nodal volumes were either SIB-66 schedule 66 Gray (Gy) prescribed to high risk (HR) planned target volume (PTV), 60 (Gy) to intermediate risk (IR) PTV and 54 Gy to low risk (LR) PTV in 30 fractions or SIB-70 schedule 70 Gy to PTV-HR, 59.4 Gy to PTV-IR and 56 Gy to PTV-LR in 33 fractions. Result: Forty-five patients were included. Forty-two patients were treated with SIB-66 schedule and three patients with SIB-70 schedule. The median follow-up period was 21 (6-68) months. There was residual disease in three patients. Recurrence was observed in 24 patients. Most recurrences were in HR volume (n = 19) and three patients had distant failure. Estimated 2-year locoregional control, disease-free survival, and overall survival were 55.55%, 49.7%, and 51.1%, respectively. Grade 3 late skin toxicity, subcutaneous fibrosis, and xerostomia were observed in three patients. Conclusions: Efficacy and late toxicity of IMRT-SIB observed in our study suggest it as a suitable treatment option for patients who are not fit for chemoradiation.

A study for evaluating clinical relevance of circulating cell-free DNA in cervical cancer.

Introduction: Recent techniques available for the detection of cervical cancer (CC) are highly invasive and costly, which makes it a rate-limiting step toward early diagnosis of this fatal disease. Evaluation of circulating cell-free DNA (ccfDNA) through liquid biopsy is a minimally invasive and cost-effective method that may serve as a unique tumor marker for early detection, treatment monitoring, the status of residual disease, and distant tumor metastasis in CC patients. Materials and Methods: In this study, initially, ccfDNA was measured in serum samples from 11 histopathologically proven cervix carcinoma patients and 8 controls. On successful screening, it was further extended to 2 more patients with a series of serum samples extracted at 3 different phases of the concurrent chemoradiotherapy (i.e., before, during, and after 6 months of follow-up). Results: Agarose gel electrophoresis profile for ccfDNA of CC patients showed that of 11 patients, 4 patients had a comparatively higher tumor burden (ccfDNA) than the other 7 patients. Notably, during concurrent chemoradiotherapy, ccfDNA load disappeared and, after 6 months of follow-up, appeared back due to distant metastasis. Conclusion: Hence, we propose that this method could be an affordable and reliable way to diagnose/screen CC.

Correlation of PD-L1 expression with toxicities and response in oropharyngeal cancers treated with definitive chemoradiotherapy.

Introduction: The programmed death receptor ligand 1 (PD-L1) is a cell-surface glycoprotein expressed in tumour cells (TCs) and is also upregulated in tumour infiltrating lymphocytes. The effect of PD-L1 expression on TCs and tumour-infiltrating lymphocytes (TILs) on acute radiation toxicity and response in oropharyngeal squamous cell carcinoma treated with concurrent chemoradiotherapy is less known. Material and methods: Squamous cell carcinoma of oropharynx with stage II-IVA (AJCC 8th) were recruited in this prospective observational study. Definitive radiation therapy (RT) of 70 Gray in 35 fractions at 2 Gray per fraction, 5 fractions a week in 2 phases was delivered with concurrent chemotherapy (cisplatin 40 mg/m2 weekly). Patients were assessed weekly for acute toxicities with Radiation Therapy Oncology Group criteria. Response assessment was done at 3 months post RT according to World Health Organization response assessment criteria. The programmed death receptor ligand 1 expression in TCs and TILs was correlated with acute toxicity and survival. Results: Of 51 patients, 20 (39.2%) had PD-L1 expression in TCs and 18 (35.3%) in TILs. Patients with PD-L1 expression in TCs had fewer grade ≥ 3 oral mucositis (25% vs. 58%; p = 0.02) and grade ≥ 3 dysphagia (25% vs. 55%; p = 0.046). The programmed death receptor ligand 1-tumour infiltrating lymphocytes positives had lower ≥ 3 grade oral mucositis (22% vs. 58%; p = 0.02) and ≥ 3 grade dysphagia (17% vs. 58%; p = 0.007). Two-year overall and progression-free survival rate for the PD-L1-tumour-positive vs. PD-L1-tumour-negative group was not different (p > 0.5). Conclusions: Positive PD-L1 expression is associated with fewer acute radiation toxicities, and this could be used as a potential biomarker.

Appraisal of historical trends in maximum and minimum temperature using multiple non-parametric techniques over the agriculture-dominated Narmada Basin, India.

In this study, the long-term trends in climatological parameters, viz., maximum temperature (TMAX) and minimum temperature (TMIN), are determined over 68 years (i.e., June 1951 to May 2019) using the gridded observation datasets (1° × 1° spatial resolution) of India Meteorological Department over the Narmada river basin, India. Multiple non-parametric techniques, viz., modified Mann-Kendall (MMK), Sen's slope (SS), and Spearman's rho (SR) tests, are used to determine monthly, seasonal, and annual trends over individual grids. The trends are also analyzed for the climatic variables spatially averaged over the entire basin to draw general conclusions on historical climate change. The results reveal a significant spatiotemporal variation in trends of TMAX and TMIN over the basin. In general, both the parameters are found to be increasing. Furthermore, the hottest months (April and May) have become hotter, and the coldest month (January) has become colder, implying a higher probability of increasing temperature extremes. Furthermore, the entire duration of 68 years is divided into two epochs of 34 years, i.e., 1951-1984 and 1985-2018, and the trend analysis of TMAX and TMIN is also carried out epoch-wise to better understand/assess the signals of climate change in recent years. In general, a relatively higher warming trend was observed in the latter epoch. As a majority of the basin area is dominated by agricultural lands, the implications of the temperature trends and their impacts on agriculture are succinctly discussed. The information reported in this study will be helpful for proper planning and management of water resources over the basin under the changing climatic conditions.

Assessment of drought trends and variabilities over the agriculture-dominated Marathwada Region, India.

Drought is considered among the most perilous events with catastrophic consequences, particularly from the agro-economic point of view. These consequences are expected to exacerbate under the increasing meteorological aberrations due to changing climate, which necessitates investigating drought variabilities. This study presents a thorough spatiotemporal assessment of drought trends and variabilities over the agriculture-dominated Marathwada Region, Maharashtra, India. The precipitation data is extracted from the India Meteorological Department (IMD) gridded product, whereas actual evapotranspiration (ET) and Evaporative Stress Index (ESI) are obtained from Global Land Evaporation Amsterdam Model (GLEAM) datasets. Standardized Precipitation Index (SPI) is used to characterize drought occurrences at multiple time frames, whereas non-parametric tests, i.e., modified Mann-Kendall (MMK) and Sen's slope (SS) tests, are employed to detect trends. The results reveal the region to be prone to droughts, and SPI at a longer time frame (i.e., 12-monthly moving frame) can capture drought occurrences better than the shorter time frames, which can be attributed to the lesser randomness in the time series in the longer frame. A mix of positive/negative trends of SPI series are found for the monsoonal months; however, they are relatively more concentrated towards negative ZMMK. Hence, the Marathwada Region can be inferred to have exhibited a relatively increased tendency towards drought occurrences. The seasonal differences in mean values and trends of rainfall, ET, and ESI are discussed in detail. Since the Marathwada Region has a monsoon-dominated climate with high agricultural importance, the information reported in this study will help in devising water management strategies to minimize the repercussions of droughts.

Evaluation of the effect of nonsurgical periodontal therapy on malondialdehyde and 8-hydroxy deoxyguanosine levels in chronic periodontitis.

Background: Reactive oxygen species released on stimulation by periodontal pathogens cause oxidation of biomolecules and play significant role in periodontal disease pathogenesis. Aim: This study aimed to evaluate the levels of oxidative by-products malondialdehyde (MDA) and 8-hydroxy deoxyguanosine (8-OHdG) as biomarkers in chronic periodontitis patients compared to healthy as well as before and after nonsurgical periodontal therapy. The correlation between biomarkers and clinical attachment level was also evaluated. Settings and Design: A total of 112 subjects were included in this study. The subjects were divided into two groups (Group I included 56 healthy subjects and Group II constituted 56 chronic periodontitis patients) on the basis of clinical periodontal parameters. Materials and Methods: Group I subjects received no treatment and were evaluated once only for clinical and oxidative stress biomarker parameters. Nonsurgical periodontal therapy was carried out in Group II patients and they were evaluated at baseline and 3 months after therapy. Results: Both salivary and serum levels of MDA and 8-OHdG were found to be increased in chronic periodontitis patients as compared to healthy subjects. After nonsurgical periodontal therapy, the levels of MDA and 8-OHdG significantly reduced. Linear correlation between clinical attachment level and oxidative stress parameters was found to be positive and highly significant. Conclusion: It can be concluded that periodontal therapy is effective in improving the oxidative stress condition.