Organ preservation for advanced laryngeal cancer: Experience with concurrent chemoradiation therapy

Introduction: The larynx is a part of the upper respiratory tract that performs many essential functions including breathing, speaking, and swallowing. For this reason, the quality of life is significantly affected by laryngeal cancer and its treatment. Therefore, the focus of management for the last few decades has been on preserving the function of a larynx without compromising survival. This study was done with the purpose of reviewing our experience of organ preservation approach with concurrent chemoradiation therapy (CCRT) for locally advanced cancers of larynx.Methods: A retrospective chart review was carried out for the data of pathology reports and clinical notes of the patients who were diagnosed with laryngeal squamous cell carcinoma and primarily treated with CCRT at our tertiary care institute from November 2010 to June 2015.Results: Of 25 patients included in the study, there were 19 males and six females. The mean age was 56 years. On comparison of post-treatment CT scan following eight weeks of completion of therapy, 21 patients showed complete resolution of the disease and four patients had persistent disease who were later treated with salvage laryngectomy. The speech was understandable in 18 patients and poor or not understandable in seven patients. Three patients had chronic aspiration and breathing difficulties necessitating permanent tracheostomy. Three patients required permanent gastrostomy due to chronic dysphagia, one of them belonged to those who were also tracheostomized.Conclusions: Our experience with CCRT as an organ preservation approach for advanced laryngeal cancers was promising. When considering the functional organ preservation, the proportion of success is remarkably less; however, the overall impression is worthy enough to uphold the sentiment in favor of non-surgical organ preservation. The debate is ongoing in the quest of finding a balanced approach with acceptable toxicity and decent functional outcome with adequate speech, breathing, and swallowing

Spatial downscaling and gap-filling of SMAP soil moisture to high resolution using MODIS surface variables and machine learning approaches over ShanDian River Basin, China

High-resolution soil moisture (SM) information is essential for regional to global hydrological and agricultural applications. The Soil Moisture Active Passive (SMAP) offers daily global composites of SM at coarse-resolution 9 and 36 km, with data gaps limiting its local application to depict SM distribution in detail. To overcome the aforementioned problem, a downscaling and gap-filling novel approach was adopted, using random forest (RF) and artificial neural network (ANN) algorithms to downscale SMAP SM data, using land-surface variables from moderate-resolution imaging spectroradiometer (MODIS) onboard Aqua and Terra satellites from the years 2018 to 2019. Firstly, four combinations (RF+Aqua, RF+Terra, ANN+Aqua, and ANN+Terra) were developed. Each combination downscaled SMAP SM at a high resolution (1 km). These combinations were evaluated by using error matrices and in situ SM at different scales in the ShanDian River (SDR) Basin. The combination RF+Terra showed a better performance, with a low averaged unbiased root mean square error (ubRMSE) of 0.034 (Formula presented.) / (Formula presented.) and high averaged correlation (R) of 0.54 against the small-, medium-, and large-scale in situ SM. Secondly, the impact of various land covers was examined by using downscaled SMAP and in situ SM. Vegetation attenuation makes woodland more error-prone and less correlated than grassland and farmland. Finally, the RF+Terra and ANN+Terra combinations were selected for their higher accuracy in gap filling of downscaled SMAP SM. The gap-filled downscaled SMAP SM results were compared spatially with China Land Data Assimilation System (CLDAS) SM and in situ SM. The RF+Terra combination outcomes were more humid than ANN+Terra combination results in the SDR basin. Overall, the RF+Terra combination gap-filled data showed high R (0.40) and less ubRMSE (0.064 (Formula presented.) / (Formula presented.)) against in situ SM, which was close to CLDAS SM. This study showed that the proposed RF- and ANN-based downscaling methods have a potential to improve the spatial resolution and gap-filling of SMAP SM at a high resolution (1 km)

Evaluation of the anti-inflammatory, antioxidant, and cytotoxic potential of Cardamine amara L. (Brassicaceae): A comprehensive biochemical, toxicological, and in silico computational study

Introduction:Cardamine amara L. (Brassicaceae) is an important edible plant with ethnomedicinal significance. This study aimed at evaluating the phytochemical composition, anti-inflammatory, antioxidant and cytotoxicity aspects of the hydro-alcoholic extract of C. amara (HAECA).Methods: The phytochemical composition was evaluated through total phenolic contents (TPC), total flavonoid contents (TFC) determination and UPLC-QTOF-MS profiling. Anti-inflammatory evaluation of HAECA was carried out through the carrageenan induced paw edema model. Four in vitro methods were applied in the antioxidant evaluation of HAECA. MTT assay was used to investigate the toxicity profile of the species against human normal liver cells (HL7702), human liver cancer cell lines (HepG2) and human breast cancer cell lines (MCF-7). Three major compounds (Gentisic acid, skullcapflavone and conidendrine) identified in UPLC-Q-TOF-MS analysis were selected for in silico study against cyclooxygenase (COX-I and COX-II).Results and Discussion: The findings revealed that HAECA is rich in TPC (39.32 ± 2.3 mg GAE/g DE) and TFC (17.26 ± 0.8 mg RE/g DE). A total of 21 secondary metabolites were tentatively identified in UPLC-Q-TOF-MS analysis. In the MTT cytotoxicity assay, the extract showed low toxicity against normal cell lines, while significant anticancer activity was observed against human liver and breast cancer cells. The carrageenan induced inflammation was inhibited by HAECA in a dose dependent manner and showed a marked alleviation in the levels of oxidative stress (catalase, SOD, GSH) and inflammatory markers (TNF-α, IL-1β). Similarly, HAECA showed maximum antioxidant activity through the Cupric reducing power antioxidant capacity (CUPRAC) assay (31.21 ± 0.3 mg TE/g DE). The in silico study revealed a significant molecular docking score of the three studied compounds against COX-I and COX-I. Conclusively the current study encourages the use of C. amara as a novel polyphenolic rich source with anti-inflammatory and antioxidant potential and warrants further investigations on its toxicity profile

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Multi-Scale Assessment of SMAP Level 3 and Level 4 Soil Moisture Products over the Soil Moisture Network within the ShanDian River (SMN-SDR) Basin, China

The Soil Moisture Active Passive (SMAP) mission with high-precision soil moisture (SM) retrieval products provides global daily composites of SM at 3, 9, and 36 km earth grids measured by L-band active and passive microwave sensors. The capability of passive microwave remote sensing has been recognized for the estimation of SM variations. The purpose of this work was to establish an interaction between the highly variable SM spatial distribution on the ground and the SMAP’s coarse resolution radiometer-based SM retrievals. In this work, SMAP Level 3 (L3) and Level 4 (L4) SM products are validated with in situ datasets observed from the different locations of the Soil Moisture Network within the ShanDian River (SMN-SDR) Basin over the period of January 2018 to December 2019. The values of the unbiased root mean square error (ubRMSE) for L3 (SPL3SMP_E) SM retrievals are close to the standard SMAP mission SM accuracy requirement of 0.04 m3/m3 at the 9-km scale, with an averaged ubRMSE value of 0.041 m3/m3 (0.050 m3/m3) for descending (ascending) SM with the correlation (R) values of 0.62 (0.42) against the sparse network sites. The L4 (SPL4SMGP) Surface and Root-zone SM (RZSM) estimates show less error (ubRMSE < 0.04) and high correlation (R > 0.60) values, and are consistent with the previous SMAP-based SM estimations. The SMAP L4 SM products (SPL4SMGP) performed well compared to the L3 SM retrieval products (SPL3SMP_E). In vegetated land, the variability and compatibility of the SMAP SM estimates with the evaluation metrics for both products (L3 and L4) showed a good performance in the grassland, then in the farmland, and worst in the woodlands. Finally, SMAP algorithm parameters sensitivity analysis of the satellite products was conducted to produce time-series and highly precise SM datasets in China

THE IMPACT OF FOREIGN DIRECT INVESTMENT ON ECONOMIC GROWTH IN PAKISTAN.

Foreign direct investment has been one of the important sources of economic growth. It will increase not only the level of incomes in host countries but also the productive base of these countries. This study has followed to identify any Granger-Causality among the economic growth and its determinants in terms of causality among Gross Domestic Product, Foreign Investment, Labour Force, Capital formation and infrastructure in a developing country context for Pakistan. The literature has abundant research work on causality analysis of FDI and economic growth. This study also adds by identifying the causal relationship among GDP and its determinants including FDI for Pakistan in time spanning from 1980 to 2008. The Error correction mechanism is adopted and Engle-Granger Causality tests has been applied to identify causal relationship among the included variables. The results indicate that FDI is not granger causing GDP for Pakistan while other important determinants Granger-causing GDP are inflation, infrastructure and trade openness, while FDI is Granger-caused by inflation, trade openness and capital formation.Keywords: Gross Domestic Product, Foreign Direct Investment, Labor Force

Breast cancer epidemiology and sociodemographic differences in BRICS-plus countries from 1990 to 2019: An age period cohort analysis

Background: Breast cancer (BC) is a major health concern in the BRICS-plus, a group of developing nations consisting of Brazil, Russia, India, China, South Africa, and 30 other Asian countries, with nearly half of the world's population. This study aims to identify potential risk factors contributing to the burden of BC by assessing its epidemiological and socio-demographic changes. Methods: Data on BC outcomes were obtained from the 2019 Global Burden of Disease Survey. The age-period-cohort (APC) modeling technique was used to evaluate the nonlinear impacts of age, cohort, and period on BC outcomes and reported risk attributable mortality and disability adjusted life years (DALYs) rate changes between 1990 and 2019. Results: In 2019, there were 0.90 million female BC cases and 0.35 million deaths in the BRICS-plus region, with China and India having the largest proportion of incident cases and deaths, followed by Pakistan. Lesotho experienced the highest annualized rates of change (AROC: 2.61%; 95%UI: 1.99–2.99) in the past three decades. Birth cohorts' impact on BC varies greatly between the BRICS-plus nations, with Pakistan suffering the largest risk increase in the most recent cohort. High body mass index (BMI), high fasting plasma glucose (FPG), and a diet high in red meat contributed to the highest death and DALYs rates in most BRICS-plus nations in 2019, and there was a strong negative link between SDI and death and DALYs rate. Conclusions: The study found that the burden of BC varies significantly between BRICS-plus regions. Thus, BRICS-plus nations should prioritise BC prevention, raise public awareness, and implement screening efficiency measures to reduce the burden of BC in the future, as well as strengthen public health policies and initiatives for important populations based on their characteristics and adaptability

Molecularly Imprinted Polymer-Silica Hybrid Particles for Biomimetic Recognition of Target Drugs

Biomimetic hybrid particles based on amlodipine-imprinted poly(methacrylic acid-co-ethylene glycol dimethacrylate) (MIP) are developed by free radical polymerization of the monomers and crosslinkers in the presence of silica nanoparticles. Atomic force microscopy is used to study the distribution and surface morphology of MIP-silica hybrid particles. The responsive properties are studied by exposing the synthesized MIP-silica hybrid material to standard amlodipine drug solution and consequently monitoring the decrease in drug concentration. The control material, i.e., nonimprinted polymer- (NIP-) silica hybrid particles, exhibits much lower response during the drug rebinding assay suggesting the lack of functionality due to the absence of imprinting effects. The selectivity of MIP-silica hybrid particles is evaluated by examining the aspirin uptake that shows lower absorbance shifts for aspirin solution compared to amlodipine. It indicates a higher sensitivity of MIP-silica hybrid particles toward targeted pharmaceutical drug recognition and also exhibits their potential for drug assay in multiplex biological samples. Furthermore, MIP-silica hybrid particles used in the drug rebinding assay can be recovered and regenerated for subsequent tests without losing recognition properties