Identification and characterization of NHX gene family for their role under salt stress in Vigna mungo.

In the current study, we have performed a comprehensive analysis of the Sodium Hydrogen Exchanger (NHX) gene family in Vigna mungo, and a total of 44 NHX genes were identified. A bimodal distribution based on domains, gene structure and phylogenetic analysis was evident. All intronpoor and intron-rich genes were clustered in clades I and II, respectively. Interestingly, all genes of subclade IIb were localized to vacuoles and possess only the NHX domain. The isoelectric point and trans-membrane domain analysis reflect the wide distribution of the NHX genes. Interestingly, Vm_NHX2 and Vm_NHX3 lacked trans-membrane domain but were found to interact with other NHX genes as well as vital salinity pathway genes, including calcium-mediated salt-responsive genes. The comparison of the mRNA sequences with that of V. marina, a halophytic species, reflects their independent evolution, majorly supporting the convergent evolution. The Ka/Ks ratio reflects the abundance of purifying selection supporting their conserved function during evolution. In our analysis, several abiotic stress and hormone-responsive elements and transcription factor binding sites were present in the promoter of the NHX genes. Further, the ion partitioning of a tolerant (K90) and a susceptible (K49) variety of V. mungo suggested that K90 managed the Na+/K+ ratio more affluently, which was also supported by profiling of superoxide radicals, hydrogen peroxide, phenol, peroxidase activity and superoxide dismutase activity. From the expression, we identified five candidate Vm_NHX genes, four of which, i.e. Vm_NHX16, Vm_NHX17, Vm_NHX29 and Vm_NHX33, were localized to the vacuolar and lysosomal membrane.

Relative importance of VECTRI model parameters in the malaria disease transmission and prevalence.

In this study, a sensitivity analysis on a VECTRI dynamical model of malaria transmission is investigated to determine the relative importance of model parameters to disease transmission and prevalence. Apart from being most climatic prone, Odisha is a highly endemic state for malaria in India. The lack in sufficient modeling studies severely impacts the malarial process studies which further hinder the possibility of malaria early warning systems and preventive measures to be undertaken beforehand. Therefore, modeling studies and investigating the relationship between malaria transmission process studies and associated climatic factors are the need of the hour. Environmental conditions have pronounced effects on the malaria transmission dynamics and abundance of the poikilothermic vectors, but the exact relationship of sensitivity for these parameters is not well established. Sensitivity analysis is a useful tool for ascertaining model responses to different input variables. Therefore, in order to perform the requisite study, a dynamical model, VECTRI, is utilized. The study period ranges from 2000 to 2013, where several sensitivity tests are performed using different model parameters such as infiltration and evaporation rate loss of ponds, degree-days for parasite development, threshold temperature for parasite development, threshold temperature for egg development in the vector, and maximum and minimum temperature for larvae survival. The experiments suggest that the lower value of minimum temperature for larvae survival (rlarv_tmin), i.e., 16 °C, provides higher vector density and entomological inoculation rate (EIR) values. EIR reaches its maximum, when the threshold temperature for parasite development (rtsporo) is 22 °C and degree-days for parasite development (dsporo) is 8 degree-days. No change is observed in the vector density; even when rtsporo is 30 °C, values of EIR are close to 0. A successive increment of infiltration and evaporation rate loss of ponds (rwaterfrac evap126) values from 130 to 200 mm/day result in approximately 5% consistent decline in vector density and EIR. The study concludes that the most sensitive parameters are dsporo, rlarv_tmin, and rwaterfrac evap126. The VECTRI model is rather insensitive to maximum temperature for larvae survival (rlarv_tmin) for vector density and EIR variables. Further certain modifications and improvements are required in VECTRI to predict out variables like vector density and EIR more accurately in highly endemic region.

Dissipation Kinetics and Residue Distribution of Imazethapyr in Urdbean (Vigna mungo (L.) Hepper) and Urdbean Field soil and its Effect on soil Microbial Population.

Imazethapyr is the most common herbicide used for weed management in pulses. A field trial was carried out with imazethapyr 10% SL formulation at 100 and 150 g a.i./ha application rates, as pre-and post-emergence, to study dissipation of imazethapyr in soil, persistence in urdbean plant, terminal residues in urdbean grains and effect on soil microbes. An acetate buffered- quick, easy, cheap, effective, rugged, and safe (QuEChERS) method in combination with high-performance liquid chromatography (HPLC) was validated for imazethapyr residue analysis. The half-life of imazethapyr in soil ranged from 15.12 to 18.02 days. The residues of imazethapyr persist up to 60 days in soil and up to 7-15 days in urdbean plant. Residues were not detected in grains at the time of harvest. Persistence of imazethapyr residues in soil significantly impact soil microbial populations depending on herbicide application rates and timing.

Expression pattern of candidate genes and their correlation with various metabolites of abscisic acid biosynthetic pathway under drought stress in rice.

Drought hampers global rice production. Abscisic acid (ABA) plays versatile roles under different environmental stresses. While the link between drought and ABA is known, its effect on ABA biosynthesis genes and metabolites is unclear. This study explored the impact of drought on various metabolites, namely beta-carotene, zeaxanthin, antheraxanthin, violaxanthin, neoxanthin, and candidate genes viz. zeaxanthin epoxidase (ZEP) and 9-cis epoxycarotenoid dioxygenase (NCED) of ABA biosynthesis pathway in rice cultivars (N22 and IR64) at anthesis {65 DAT (Days after transplanting)} with different stress levels. In stressed plants, zeaxanthin significantly increased (92%), while the concentration of beta-carotene, antheraxanthin, violaxanthin and neoxanthin decreased as drought stress progressed. The concentration of metabolites in roots was notably lower than in leaves in both genotypes. The ZEP expression was upregulated in roots (8.24-fold) under drought stress. Among five NCED isoforms, NCED3 showed significant upregulation (7.29-fold) in leaf and root tissue. NCED1 was significantly downregulated as stress progressed and was negatively correlated with ABA accumulation. NCED2, NCED4 and NCED5 showed no significant change in their expression. Drying and rolling of rice leaves was observed after imparting drought stress. The findings revealed that drought stress significantly influenced the expression of candidate genes and the concentration of metabolites of the ABA biosynthesis pathway. There was a significantly higher accumulation of ABA in N22 leaves (47%) and roots (30%) compared to IR64. The N22, a drought-tolerant genotype, exhibited significantly higher concentrations of intermediates and demonstrated increased expression of ZEP and NCED3, potentially contributing to its resilience against drought.

Isolation and characterization of drought and ABA responsive promoter of a transcription factor encoding gene from rice.

Water deficit is a significant impediment to enhancing rice yield. Genetic engineering tools have enabled agriculture researchers to develop drought-tolerant cultivars of rice. A common strategy to achieve this involves expressing drought-tolerant genes driven by constitutive promoters such as CaMV35S. However, the use of constitutive promoters is often limited by the adverse effects it has on the growth and development of the plant. Additionally, it has been observed that monocot-derived promoters are more successful in driving gene expression in monocots than in dicots. Substitution of constitutive promoters with stress-inducible promoters is the currently used strategy to overcome this limitation. In the present study, a 1514 bp AP2/ERF promoter that drives the expression of a transcription factor was cloned and characterized from drought-tolerant Indian rice genotype N22. The AP2/ERF promoter was fused to the GUS gene (uidA) and transformed in Arabidopsis and rice plants. Histochemical GUS staining of transgenic Arabidopsis plants showed AP2/ERF promoter activity in roots, stems, and leaves. Water deficit stress and ABA upregulate promoter activity in transformed Arabidopsis and rice. Quantitative PCR for uidA expression confirmed induced GUS activity in Arabidopsis and rice. This study showed that water deficit inducible Os-AP2/ERF-N22 promoter can be used to overcome the limitations of constitutive promoters. Transformants overexpressing Os-AP2/ERF-N22 showed higher relative water content, membrane stability index, total chlorophyll content, chlorophyll stability index, wax content, osmotic potential, stomatal conductance, transpiration rate, photosynthetic rate and radical scavenging activity. Drought tolerant (N22) showed higher expression of Os-AP2/ERF-N22 than the susceptible (MTU1010) cultivar. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01246-9.

Temporal Changes in Treatment Patterns for Rural and Urban Patients With Early-Stage Non-Small Cell Lung Cancer.

BACKGROUND Our objectives were to evaluate geographic access to lung cancer treatment modalities in North Carolina and to characterize how practice patterns are changing over time. We hypothesized that rural patients would be less likely to undergo treatment compared to urban patients, with widening disparities over time.METHODS We identified patients with Stage I non-small cell lung cancer (NSCLC) from 2006 to 2015 using the North Carolina Central Cancer Registry linked with Medicaid, Medicare, and private insurance claims. The primary outcome was first-course treatment: surgery, radiation, or no treatment. Calendar years were split into earlier (2006-2010) and later (2011-2015) periods. We estimated the adjusted odds ratio (OR) of rural/urban status and time period with 1) surgery and 2) any treatment (surgery or radiation) using multivariable logistic regression.RESULTS Among 5504 patients, 3206 (58%) underwent surgery as initial therapy, 1309 (24%) received radiation as initial therapy, and 989 (18%) had no therapy. There were no rural-urban disparities in treatment patterns. For rural and urban patients, the odds of surgery decreased over time and the odds of radiation increased. We also found that only 48% of those receiving no treatment ever reached a surgeon or radiation oncologist.LIMITATIONS This was an insured, single-state population. Treatment preferences are unknown.CONCLUSIONS Among all treated patients, whether urban or rural, there was increasing use of radiation and decreasing use of surgery over time. Many patients without treatment never had a consultation with a surgeon/radiation oncologist, and this is an actionable target for improving treatment access for early-stage NSCLC.

Biomarker-based evaluation of cytogenotoxic potential of glyphosate in Vigna mungo (L.) Hepper genotypes.

Herbicides have proven to be a boon for agricultural fields. Their inherent property to kill weeds and unwanted vegetation makes them an essential biological tool for farmers and agricultural systems. Besides being capable of destroying weeds, they also exhibit certain effects on non-target crop plants. In the present study, a laboratory experiment was performed to assess the effect of glyphosate on Vigna mungo root meristem cells. Seeds of five different genotypes of V. mungo were treated with a series of concentrations of glyphosate ranging from 1 to 10 mM, and their effects on mitotic cell division were studied. Healthy and uniform-sized seeds were selected and were allowed to grow in Petri plates for 3 days, and all the doses were maintained in triplicates. Roots were fixed at day 3 after treatment (DAT) for cytological microscopic slide preparation. The results obtained indicate the dose-dependent reduction in the mitotic index in all the genotypes and an increase in the percentage of chromosomal aberrations (CAs) and relative abnormality rate (RAR). Most commonly observed chromosome aberrations at lower doses (< 6 mM) were fragments, stickiness, and disoriented metaphase, while at higher doses (6 to 10 mM) bridges, laggards, spindle disorientation, and clumping were obvious. The increase in the percentage of CAs and RAR indicates the inhibitory effect of glyphosate on cell cycle progression at various stages in root tip cells. The present study is a fine example of a biomarker-based genotoxic assessment of mitotic damage caused by glyphosate.

D-Dimer Enhances Risk-Targeted Thromboprophylaxis in Ambulatory Patients with Cancer.

BACKGROUND: Thromboprophylaxis for ambulatory patients with cancer is effective, although uncertainties remain on who should be targeted. Using D-dimer values from individuals enrolled to the AVERT trial, we sought to identify and validate a more efficient venous thromboembolism (VTE) risk threshold for thromboprophylaxis. MATERIALS AND METHODS: The AVERT trial compared thromboprophylaxis with apixaban with placebo among patients with cancer with a Khorana Risk Score ≥2. The D-dimer measured at randomization was used to calculate an individualized 6-month VTE risk using the validated CATScore. A modified intention-to-treat analysis was used to assess efficacy (VTE) and safety (major and overall bleeding) in the (a) complete cohort and (b) ≥8% and < 8% 6-month VTE risk thresholds. RESULTS: Five hundred seventy-four patients were randomized in the AVERT trial; 466 (81%) with baseline D-dimer were included in the study. Two hundred thirty-seven subjects received apixaban; 229 received placebo. In the complete cohort, there were 13 (5.5%) VTE events in the apixaban arm compared with 26 (11.4%) events in the placebo arm (adjusted hazard ratio [aHR] 0.49 [0.25-0.95], p < .05). Number needed to treat (NNT) to prevent one VTE = 17. Eighty-two (35%) and 72 (31%) patients in the apixaban and placebo arms, respectively, had a 6-month VTE risk ≥8%. In this subgroup, 7 (8.4%) VTE events occurred with apixaban and 19 (26.3%) events with placebo (aHR 0.33 [0.14-0.81], p < .05), NNT = 6. Individuals with a VTE risk <8% derived no benefit from apixaban thromboprophylaxis (aHR 0.89 [0.30-2.65), p = .84). Increased rates of overall bleeding were observed with apixaban in both the complete (aHR 2.11 [1.09-4.09], p < .05) and ≥ 8% predicted risk cohorts (aHR 2.87 [0.91-9.13], p = .07). CONCLUSION: A 6-month VTE risk threshold of ≥8% increases the efficiency of risk-targeted thromboprophylaxis in ambulatory patients with cancer. IMPLICATIONS FOR PRACTICE: Ambulatory patients with cancer receiving chemotherapy have an increased risk of venous thromboembolism (VTE). A Khorana Risk Score (KRS) ≥2 is currently the suggested threshold for thromboprophylaxis. Using baseline D-dimer values from individuals enrolled to the AVERT trial, this retrospective validation study identifies a 6-month VTE risk of ≥8% as a more efficient threshold for thromboprophylaxis. At this threshold, the number needed to treat to prevent one VTE is 6, compared with 17 when using a KRS ≥2. Conversely, individuals with a predicted risk of <8% derive no clinical benefit from thromboprophylaxis. Future prospective studies should validate this threshold for outpatient thromboprophylaxis.

Risk-Targeted Lung Cancer Screening: A Cost-Effectiveness Analysis.

Background: Targeting low-dose computed tomography (LDCT) for lung cancer screening to persons at highest risk for lung cancer mortality has been suggested to improve screening efficiency. Objective: To quantify the value of risk-targeted selection for lung cancer screening compared with National Lung Screening Trial (NLST) eligibility criteria. Design: Cost-effectiveness analysis using a multistate prediction model. Data Sources: NLST. Target Population: Current and former smokers eligible for lung cancer screening. Time Horizon: Lifetime. Perspective: Health care sector. Intervention: Risk-targeted versus NLST-based screening. Outcome Measures: Incremental 7-year mortality, life expectancy, quality-adjusted life-years (QALYs), costs, and cost-effectiveness of screening with LDCT versus chest radiography at each decile of lung cancer mortality risk. Results of Base-Case Analysis: Participants at greater risk for lung cancer mortality were older and had more comorbid conditions and higher screening-related costs. The incremental lung cancer mortality benefits during the first 7 years ranged from 1.2 to 9.5 lung cancer deaths prevented per 10 000 person-years for the lowest to highest risk deciles, respectively (extreme decile ratio, 7.9). The gradient of benefits across risk groups, however, was attenuated in terms of life-years (extreme decile ratio, 3.6) and QALYs (extreme decile ratio, 2.4). The incremental cost-effectiveness ratios (ICERs) were similar across risk deciles ($75 000 per QALY in the lowest risk decile to $53 000 per QALY in the highest risk decile). Payers willing to pay $100 000 per QALY would pay for LDCT screening for all decile groups. Results of Sensitivity Analysis: Alternative assumptions did not substantially alter our findings. Limitation: Our model did not account for all correlated differences between lung cancer mortality risk and quality of life. Conclusions: Although risk targeting may improve screening efficiency in terms of early lung cancer mortality per person screened, the gains in efficiency are attenuated and modest in terms of life-years, QALYs, and cost-effectiveness. Primary Funding Source: National Institutes of Health (U01NS086294).

Fluoride, Thyroid Hormone Derangements and its Correlation with Tooth Eruption Pattern Among the Pediatric Population from Endemic and Non-endemic Fluorosis Areas.

AIM: To comparatively evaluate the status of fluoride in the body with thyroid activity in the pediatric population of endemic fluorosis areas. The present study also attempted to elucidate whether any correlation exists between fluoride and thyroid hormone derangement with delayed tooth eruption. MATERIALS AND METHODS: A total of 400 pediatric subjects were included in the present study. All the patients were divided into two broad groups; groups A and B. Group A included 200 subjects who belonged to the endemic fluorosis area while Group B included remaining 200 subjects, who belonged to the fluorosis non-endemic area. Group B subjects were taken as control. Group A subjects were further divided into two study groups as follows: Group A1: 100 Pediatric subjects with dental fluorosis, and Group A 2: A total of one hundred pediatric subjects without dental fluorosis. Dean's index of fluorosis was calculated in all the patients. Blood samples were collected and were sent to a laboratory for assessment of thyroid hormone levels. All the results were subjected to statistical analysis by Statistical Package for the Social Sciences (SPSS) software. RESULTS: Mean thyroid stimulating hormone (TSH), water fluoride levels, urine fluoride levels and serum fluoride levels of subjects in group 1 were found to be significantly higher than that of subjects of group 2. Delayed tooth eruption was absent in subjects of group B while it was present in 100 subjects of group A. Thyroid hormone level derangement was seen in 54 percent subjects of group B, while it was seen in 67.5% subjects of group A. CONCLUSION: Positive correlation exists between fluorosis and thyroid functional activity. However; the tooth eruption pattern is independent up on the thyroid hormone derangement. CLINICAL SIGNIFICANCE: Delayed tooth eruption and alteration in thyroid hormone levels can occur in subjects of the endemic fluoride areas. Therefore, adequate measures should be taken for controlling such adverse effects.

Comparative Evaluation of Different Bone Markers in Peri-implant Crevicular Fluid of Immediate Loaded and Nonloaded Dental Implants.

AIM: The present study was conducted to determine different bone markers in immediate loaded and nonloaded dental implants. MATERIALS AND METHODS: It comprised of 60 patients (males-30, females-30) which were divided into two groups of 30 each. Group I received immediate loaded dental implants, and group II received non-loaded dental implants. Modified bleeding on probing index, peri-implant sulcus depth was assessed in both groups at 1 month, 2 months, 3 months and 4 months. The crevicular fluid was obtained to determine bone markers levels such as transforming growth factor-alpha (TGF-a), osteocalcin (OCN), osteopontin (OPN), parathyroid hormone (PTH) and osteoprotegerin (OPG). RESULTS: Both groups revealed non-significant difference in modified bleeding on probing index and peri-implant sulcus depth (p > 0.05). Bone markers found to be elevated more in group I as compared to group II. However, the difference was non- significant (p > 0.05). CONCLUSION: Transforming growth factor alpha (TGF-a), OCN, OPN, OPG and PTH and parathyroid hormone (PTH) levels were higher in immediate loaded dental implants as compared to nonloaded dental implants. CLINICAL SIGNIFICANCE: Immediate loaded dental implants showed an increase in expression of bone markers such as TNF-a, OCN, OPN, PTH and OPG which may be useful in deciding future of immediate loaded dental implants.

Molecular cloning, heterologous expression and functional characterization of gamma tocopherol methyl transferase (γ-TMT) from Glycine max.

γ-Tocopherol methyltransferase (γ-TMT) (EC 2.1.1.95) is the last enzyme in the tocopherol biosynthetic pathway and it catalyzes the conversion of γ-tocopherol into α-tocopherol, the nutritionally significant and most bioactive form of vitamin E. Although the γ-TMT gene has been successfully overexpressed in many crops to enhance their α-tocopherol content but still only few attempts have been made to uncover its structural, functional and regulation aspects at protein level. In this study, we have cloned the complete 909bp coding sequence of Glycine max γ-TMT (Gm γ-TMT) gene that encodes the corresponding protein comprising of 302 amino acid residues. The deduced Gm γ-TMT protein showed 74-87% sequence identity with other characterized plant γ-TMTs. Gm γ-TMT belongs to Class I Methyl Transferases that have a Rossmann-like fold which consists of a seven-stranded ß sheet joined by α helices. Heterologous expression of Gm γ-TMT in pET29a expression vector under the control of bacteriophage T7 promoter produced a 37.9 kDa recombinant Gm γ-TMT protein with histidine hexamer tag at its C-terminus. The expression of recombinant Gm γ-TMT protein was confirmed by western blotting using anti-His antibody. The recombinant protein was purified by Ni2+-NTA column chromatography. The purified protein showed SAM dependent methyltransferase activity. The α-tocopherol produced in the in-vitro reaction catalyzed by the purified enzyme was detected using reverse phase HPLC. This study has laid the foundation to unveil the biochemical understanding of Gm γ-TMT enzyme which can be further explored by studying its kinetic behaviour, substrate specificity and its interaction with other biomolecules.

The potential use of mass timber in mid-to high-rise construction and the associated carbon benefits in the United States.

Nonresidential and mid- to high-rise multifamily residential structures in the United States currently use little wood per unit floor area installed, because earlier building codes lacked provisions for structural wood use in those types of buildings. However, revisions to the International Building Code allow for increased wood use in the form of mass timber, as structural and fire safety concerns have been addressed through new science-based design standards and through newly specified construction materials and measures. This study used multiple models to describe alternative futures for new construction, mass timber adoption rates, and the associated carbon benefits in higher than three-story buildings in the United States. The use of mass timber, in place of traditional constructions (i.e., structures dominated by concrete and steel), in projected new higher than three-story buildings was shown to provide combined carbon benefits (i.e., global warming mitigation benefits), including avoided embodied carbon emissions due to the substitution of non-wood alternatives and additional biogenic carbon storage in mass timber materials, of between 9.9 and 16.5 million t CO2e/yr spanning 50 years, 2020 to 2070. These carbon benefits equate to 12% to 20% of the total U.S. harvested wood products carbon storage for 2020. Future research is needed to understand how greater mass timber adoption leads to changes in forest product markets, land use, and total forest sector carbon.

Data and bills of materials for buildings designed for mass timber, structural steel, and reinforced concrete based on the 2021 international building code provisions.

This article presents and describes a dataset for the bills of materials for the buildings constructed with mass timber (MT), structural steel (SS), and reinforced concrete (RC), which are generated using Athena's Impact Estimator for Buildings (IE4B) software to conduct a whole building life-cycle assessment (WBLCA). These data are associated with the research article Environmental Impact Assessment of Mass Timber, Structural Steel, and Reinforced Concrete Buildings Based on the 2021 International Building Code Provisions [1]. This dataset was utilized to estimate their environmental impacts but can be used to estimate the costs of buildings constructed with MT, SS, and RC building materials. These data could be replicated using the same layout, system boundaries, reference study period (RSP), and building assemblies' information as used in the published work [1]. This dataset is related to conceptual design of a building with 11 apartment units per floor. However, a detailed design that includes the analysis of interior architectural finishes such as internal partitions within the units, kitchen and washroom fixtures, internal doors, flooring, and so on, could be developed and analyzed to obtain a more comprehensive estimates of life cycle assessment. This dataset was originally developed to compare the environmental impacts of structural materials selection for three common framing typologies.

"Effectiveness of minimally invasive injectable modalities in the management of androgenetic alopecia among adults-A systematic review".

BACKGROUND: Androgenetic alopecia is the most common cause of hair loss that affects over 50% of the world population. It is a condition that is multifactorial in origin, with no specific causative factor, making treatment an enervating experience for the patient as well as the doctor. In recent times, a number of modalities have been introduced for the treatment of alopecia. However, the evidence supporting them is unstructured and sparse. Therefore, this article aims to explore the current trends in minimally invasive treatments for the management of androgenetic alopecia. METHODS: An in-depth literature search on injectables used in the treatment of alopecia in PubMed/MEDLINE, Embase, PsycINFO, TRIP Cochrane Library, and Cochrane Skin databases between January 2000 and May 2023 was performed. The studies included were randomized controlled trials, non-randomized trials, quasi trials, single arm interventions, and cohort studies. RESULTS: Sixteen of the 1071 studies that were found during the original search were accepted in accordance with the inclusion criteria. Twelve studies assessed the effectiveness of the injectable group by comparing it to a control group consisting of saline, distilled water, and topical minoxidil. In the treatment of alopecia, dutasteride and injectable growth factor formulations achieved clinically significant results. CONCLUSION: The usage of injectables and topical medicines to treat hair loss has increased in the recent years. Overall results from clinical investigations, pilot studies, and trials looking at the efficacy and safety of these growth factors in the AGA show satisfactory efficacy.

FDA Approval Summary: Durvalumab and Pembrolizumab, Immune Checkpoint Inhibitors for the Treatment of Biliary Tract Cancer.

On September 2, 2022, the Food and Drug Administration (FDA) approved durvalumab in combination with cisplatin and gemcitabine, for the treatment of patients with unresectable or metastatic biliary tract cancers (BTC). On October 31, 2023, the FDA approved pembrolizumab in combination with cisplatin and gemcitabine for the same indication. Approvals were based on two randomized, multiregional, placebo-controlled trials that randomly allocated patients to receive durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966) in combination with chemotherapy or placebo in combination with chemotherapy. Overall survival (OS) was the primary endpoint in both studies. In both studies, a statistically significant and clinically meaningful improvement in OS was demonstrated. In the TOPAZ-1 trial, the median OS of patients receiving durvalumab was 12.8 months [95% confidence interval (CI), 11.1-14.0] and 11.5 months (95% CI, 10.1-12.5) in patients receiving placebo [hazard ratio (HR), 0.80 (95% CI, 0.66-0.97)]. In the KEYNOTE-966 trial, the median OS of patients receiving pembrolizumab was 12.7 months (95% CI, 11.5-13.6) and 10.9 months (95% CI, 9.9-11.6) in patients receiving placebo [HR, 0.83 (95% CI, 0.72-0.95)]. The addition of checkpoint inhibitors to standard of care chemotherapy for this indication did not reveal any new adverse event signals, and the safety profile was generally consistent with the known clinical experience with durvalumab, pembrolizumab, and the backbone chemotherapy regimen. The approvals of durvalumab and pembrolizumab in combination with standard of care cisplatin and gemcitabine for the treatment of unresectable or metastatic BTC add two new therapeutic options for these patients.

Toxicity assessment of metribuzin and its amelioration through plant growth regulators in Vigna radiata (L.) R. Wilczek.

The present experiment was conducted to evaluate the metribuzin-induced stress response in Vigna radiata and to explore the ameliorative role of exogenous application of plant growth regulators (PGRs) against metribuzin toxicity by assessing important biochemical and yield parameters. Prior to the field experiment, dose standardization experiments were performed, and EC50 was calculated for metribuzin. On day 21, field grown V. radiata plants were treated with graded concentrations of metribuzin (0-1000 mg [Formula: see text]). Plants treated with 600 mg [Formula: see text] (EC50) and 1000 mg [Formula: see text] (highest dose) of metribuzin were co-treated individually and simultaneously with gibberellic acid-3 (GA), indole-3 acetic acid (IAA), and salicylic acid (SA). After 7 days of treatment, leaf tissues were analyzed for biochemical parameters, whereas those related to yield were recorded during harvest. The result of this study indicated that metribuzin treatment to V. radiata resulted in increase in lipid peroxidation and reduce chlorophyll and carotenoid contents as well as yield parameters. However, metribuzin-treated plants induced proline accumulation and activity of antioxidant enzymes. Exogenous application of GA, IAA, and SA significantly reduced lipid peroxidation and increased contents of photosynthetic pigments, proline, and antioxidant enzymes thereby increasing yield parameters. It was observed that during metribuzin stress, SA exhibited a better ameliorative response out of the three exogenously applied PGRs, while the combined use of all PGRs exhibited much improved ameliorative response on biochemical and yield parameters of plants.

Dynamic routing for efficient waste collection in resource constrained societies.

Waste collection in developing nations faces multi-fold challenges, such as resource constraints and real-time changes in waste values, while finding the optimal routes. This paper attempts to address these challenges by modeling real-time waste values in smart bins and Collection Vehicles (CV). Further, waste value prioritized routes for coordinated CV, during various time intervals are modeled in a multi-agent environment for finding good routes. The CV, as agents, implement the formulated linear program to maximize the collected waste while minimizing the distance to the central depot. The city of Chandigarh, India, was divided into regions and the model was implemented to achieve significantly better performance in terms of waste collected in less distance and total bins covered when compared to the existing scenario. The stakeholders can use the outcomes to effectively plan the resources for better collection practices, which will have a positive impact on the environment.