Coumarin as an Elite Scaffold in Anti-Breast Cancer Drug Development: Design Strategies, Mechanistic Insights, and Structure-Activity Relationships.

Breast cancer is the most common cancer among women. Currently, it poses a significant threat to the healthcare system due to the emerging resistance and toxicity of available drug candidates in clinical practice, thus generating an urgent need for the development of new potent and safer anti-breast cancer drug candidates. Coumarin (chromone-2-one) is an elite ring system widely distributed among natural products and possesses a broad range of pharmacological properties. The unique distribution and pharmacological efficacy of coumarins attract natural product hunters, resulting in the identification of numerous natural coumarins from different natural sources in the last three decades, especially those with anti-breast cancer properties. Inspired by this, numerous synthetic derivatives based on coumarins have been developed by medicinal chemists all around the globe, showing promising anti-breast cancer efficacy. This review is primarily focused on the development of coumarin-inspired anti-breast cancer agents in the last three decades, especially highlighting design strategies, mechanistic insights, and their structure-activity relationship. Natural coumarins having anti-breast cancer efficacy are also briefly highlighted. This review will act as a guideline for researchers and medicinal chemists in designing optimum coumarin-based potent and safer anti-breast cancer agents.

A retrospective study of outcomes and the validation of the Sheffield Gastrostomy Score in PEGs, RIGs and PIGs.

INTRODUCTION: There are limited studies comparing the safety and effectiveness of Radiologically Assisted Gastrostomies (RAGs) against Percutaneous Endoscopic Gastrostomies (PEGs). The Sheffield Gastrostomy Score (SGS) can be used to help predict 30-day mortality, more information is needed on its validity in RAGs. Our aim is to compare mortality between RAGs (Radiologically Inserted Gastrostomies (RIGs) and Per-oral Image Guided Gastrostomies (PIGs)) with PEGs and validate the SGS. METHOD: Data on gastrostomies newly inserted in three hospitals from 2016-2019 were retrospectively collected. Demographics, indication, insertion date, date of death, inpatient status and blood tests (albumin, CRP and eGFR) were recorded. RESULTS: 1977 gastrostomies were performed: Gastrostomy mortality at 7 days was 1.3% and at 30 days was 6%. There was a 5% 30-day mortality for PEGs, 5.5% RIGs, 7.2% PIGs (p = 0.215). Factors increasing 30 day mortality were age ≥60 years (p = 0.039), albumin <35 g/L (p = 0.005), albumin <25 g/L (p < 0.001) and CRP ≥10 mg/L (p < 0.001). For patients who died within 30 days; 0.6% had an SGS of 0, 3.7% = 1, 10.2% = 2 and 25.5% = 3, with similar trends for RAGs and PEGs. ROC curves showed the area under the curve for all gastrostomies, RAGs and PEGs as 0.743, 0.738, 0.787 respectively. DISCUSSION: There was no significant difference between 30-day mortality for PEGs, RIGs and PIGs. Factors predicting risk include age ≥60 years, albumin <35 g/L, albumin <25 g/L and CRP ≥10 mg/L. The SGS has been validated in this study for PEGs and for the first time in RAGs as well..

Corrigendum: Sub-surface drip fertigation improves seed cotton yield and monetary returns.

[This corrects the article DOI: 10.3389/fpls.2022.1038163.].

Is #SDG13 Trending Online? Insights from Climate Change Discussions on Twitter.

Anthropogenic activities over the past few decades have led to increased vulnerability of environmental and ecological stability on this planet. Accelerated climate change is one such subset of the environmental problems that threatens the very existence of humankind in twenty first century. Governments, United Nations (UN) and other humanitarian agencies across the globe have developed and devised strategies for climate action that requires grater public awareness and actions. Social media has played a vital role in information dissemination and raising public awareness of climate change in the digital era. To this aid, an upsurge has been documented in recent times regarding discussions over climate change with #SDG13 (Sustainable Development Goals) at its epicenter. Following the principles of Actor Network Theory (ANT) we analyzed a large volume of Twitter data to understand general citizens' perception and attitude towards climate change. Our findings unveil people's opinion on causes and concerns related to barriers of adopting a more sustainable consumption and lifestyle practice. There is also a growing apathy towards sluggish government actions that makes little difference. People were also found to exchange innovative concepts and measures towards mitigating the effects of climate change.

Sub-surface drip fertigation improves seed cotton yield and monetary returns.

Surface flood (SF) method is used to irrigate cotton in India, which results in huge wastage of water besides leaching of nutrients. This necessitates the adoption of efficient management strategies to save scarce water without compromising the yield. Therefore, a 2-year field investigation was conducted under two climatic regimes (Faridkot and Abohar) to study the effect of sub-surface drip fertigation (SSDF) on seed cotton yield (SCY), water productivity, nitrogen use efficiency (NUE), and economic parameters in comparison with SF and surface drip fertigation (SDF). The field experiment had a total of eight treatments arranged in a randomized complete block design. Three levels of sub-surface drip irrigation [(SSDI); i.e., 60%, 80%, and 100% of crop evapotranspiration (ETc)] and two N fertigation levels [100% recommended dose of nitrogen (RDN; i.e., 112.5 kg N ha-1) and 75% RDN] made up six treatments, while SF (Control 1) and SDF at 80% ETc (Control 2), both with 100% of RDN, served as the controls. Among irrigation regimes, the SSDI levels of 80% ETc and 100% ETc recorded 18.7% (3,240 kg ha-1) and 21.1% (3,305 kg ha-1) higher SCY compared with SF (2,728 kg ha-1). Water use efficiency under SF (57.0%) was reduced by 34.2%, 40.8%, and 38.2% compared with SSDI's 60 (76.5%), 80 (80.3%), and 100% ETc (78.8%), respectively. Among fertigation levels, NUE was higher by 19.2% under 75% (34.1 kg SCY kg-1 N) over 100% RDN (28.6 kg SCY kg-1 N), but later it also registered 11.9% higher SCY, indicating such to be optimum for better productivity. SSDF at 80% ETc along with 112.5 kg N ha-1 recorded 26.6% better SCY (3455 kg ha-1) and 18.5% higher NUE (30.7 kg SCY kg-1 N) over SF. These findings demonstrate that the application of SSDF could save irrigation water, enhance SCY, and improve the farmers' returns compared with SF. Therefore, in northwestern India, SSDF at 80% ETc along with 112.5 kg N ha-1 could be a novel water-savvy concept which would be immensely helpful in enhancing cotton productivity.

Cytomegalovirus Infection in Postrenal Transplant Recipients: 18 Years' Experience From a Tertiary Referral Center.

BACKGROUND: Cytomegalovirus (CMV) reactivation or infection is one of the most important infectious complications in transplant recipient leading to significant morbidity and mortality. Its early detection and prompt treatment is imperative to improve transplant outcome. The present study estimated the frequency of CMV in renal transplant recipients (RTR). Various aspects of pp65Ag assay and quantitative real-time polymerase chain reaction (qRT-PCR) were evaluated in relation to the recent guidelines for CMV detection and treatment. METHODS: Retrospectively, data of clinically suspected cases of CMV (1610 out of total 2681 renal transplants) were analyzed along with a comparison of pp65Ag assay and qRT-PCR. RESULTS: The overall incidence of CMV syndrome was 14.25%; however, the incidence of CMV viremia in the clinically suspected group was 23.73%. The proportion of positive cases with pp65Ag assay and qRT-PCR were 13.6% (95% CI; 7.9-22.3) and 19.3% (95% CI; 12.4-28.8) with a substantial agreement (Cohen's kappa = 0.632) between the 2 techniques. CMV positive recipients were treated with ganciclovir until their viral count was negative or up to 3 weeks, followed by 3 months of prophylaxis with valganciclovir. No graft failure or mortality was reported secondary to CMV infection until 3 to 5 years of follow-up. RESULTS: CMV infection is quite prevalent in RTR, and early detection and immediate treatment or prophylaxis is of utmost importance. qRT-PCR is the gold standard and preferred over other methods; however pp65Ag assay still holds its importance in low-economic countries and populations where CMV infection is more prevalent and financial constraints are a major limitation.