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A high-yielding and well-adapted wheat variety for central and peninsular India HD2932 was improved for three types of wheat rusts by introgressing genes Lr19/Sr25, Lr24/Sr24and Yr10and a new variety HD3407 (Unnat HD2932) was developed. The linked genes, Lr19/Sr25and Lr24/Sr24, were derived from Thinopyrum(syn. Agropyron), whereas Yr10was derived from Moro wheat (Triticum aestivumL.). NILs (> 90% RPG) with Lr19/Sr25 and Lr24/Sr24in BC2F1generation were intercrossed to produce two gene combinations Lr19/Sr25+ Lr24/Sr24.The two genes carrying plants were crossed with the third NIL with Yr10for stripe rust resistance. Three-way cross NILF1s were selfed and a large F2generation was produced to select plants with three genes. A single plant with all three genes in the homozygous state and maximum phenotypic and genotypic similarity (RPG = 98.14%) was identified and nominated in all India coordinated trials as HD3407. The proposed entry HD3407 yielded at par as that of the recurrent parent and check variety HD2932 during both the years of testing, 2020–21 and 2021–22, and displayed a high degree of resistance to leaf, stem and stripe rusts at seedling and adult plant stages. The average coefficient of infection for leaf rust (1.95), stem rust (3.45) and stripe rust (6.4) in HD3407 is found to be very low in artificial conditions in comparison with recurrent parent and check HD2932. Variety HD3407 (Unnat HD2932) was released for cultivation in 2023 for the central zone of India with Gazette notification S.O. 1056(E), dated 6th March, 2023.

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Byline: Priyanka Agarwal Data on migration can play an integral role towards achieving Sustainable Development Goals. Lack of it is a big spoiler 'The 21st century is the century of [...]

Byline: Sukanya Bhaumik and Priyanka Agarwal With over 446 million internet users, India is the second largest online market but the rural-urban gap continues to be massive Safer Internet Day [...]

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Malaria is still a complex and lethal parasitic infectious disease, despite the availability of effective antimalarial drugs. Resistance of malaria parasites to current treatments necessitates new antimalarials targeting P. falciparumproteins. The present study reported the design and synthesis of a series of a 2-(4-substituted piperazin-1-yl)-N-(5-((naphthalen-2-yloxy)methyl)-1,3,4-thiadiazol-2-yl)acetamide hybrids for the inhibition of Plasmodium falciparumdihydrofolate reductase (PfDHFR) using computational biology tools followed by chemical synthesis, structural characterization, and functional analysis. The synthesized compounds were evaluated for their in vitroantimalarial activity against CQ-sensitive PfNF54 and CQ-resistant PfW2 strain. Compounds T5and T6are the most active compounds having anti-plasmodial activity against PfNF54 with IC50values of 0.94 and 3.46 μM respectively. Compound T8is the most active against the PfW2 strain having an IC50of 3.91 μM. Further, these active hybrids (T5, T6, and T8) were also evaluated for enzyme inhibition assay against PfDHFR. All the tested compounds were non-toxic against the Hek293 cell line with good selectivity indices. Hemolysis assay also showed non-toxicity of these compounds on normal uninfected human RBCs. In silicomolecular docking studies were carried out in the binding pocket of both the wild-type and quadruple mutant Pf-DHFR-TS to gain further insights into probable modes of action of active compounds. ADME prediction and physiochemical properties support their drug-likeness. Additionally, they were screened for antileishmanial activity against L. donovanipromastigotes to explore broader applications. Thus, this study provides molecular frameworks for developing potent antimalarials and antileishmanial agents.

Byline: Priyanka Agarwal June 12 is the World Day against Child Labour The fact that the World Day against Child Labour is still marking our calendars is itself disturbing. The [...]

Purpose: The present study provides evidence on export advantages of horticultural commodities based on competitiveness, trade balance and seasonality dimensions. Design/methodology/approach: The study delineated horticultural commodities in terms of comparative advantage, examined temporal shifts in export advantages (mapping) and estimated seasonality. Product mapping was carried out using the Revealed Symmetric Comparative Advantage (RSCA) and Trade Balance Index (TBI). Seasonal advantages were examined through a graphical approach along with the objective tests, namely, modified QS-test (QS), Friedman-test (FT) and using a seasonal dummy. Findings: Cucumbers/gherkins, onions, preserved vegetables, fresh grapes, shelled cashew nuts, guavas, mangoes, and spices emerged as the most favorable horticultural products. India has a strong seasonal advantage in dried onions, cucumber/gherkins, shelled cashew nut, dried capsicum, coriander, cumin, and turmeric. The untapped potential in horticulture can be addressed by handling the trade barriers effectively, particularly the sanitary and phytosanitary issues, affecting the exports. Proper policies must be enacted to facilitate the investment in advanced agricultural technologies and logistics to ensure the desired quality and cost effectiveness. Research limitations/implications: Commodity-specific studies on value chain analysis would provide valuable insights into the issues hindering exports and realizing the untapped export potential. Originality/value: There is no holistic and recent study illustrating the horticulture export advantages covering a large number of commodities in the Indian context. The study would be helpful to the stakeholders for drawing useful policy implications.

AbstractThe coronavirus disease (COVID-19) is upsetting human well-being and the economy around the globe. Scientists have been trying some antiviral drugs to control the disease and transmission of the 2019-nCoV in vitro. Two of these compounds are Favipiravir (T–705) and Ribavirin. Topological index also known as connectivity index, is a molecular descriptor which is calculated based on the molecular graph of a chemical compound. Topological indices are used to predict different biological and physicochemical properties of chemical compounds. In this article, various significant topological degree-based indices and the M-polynomials are investigated for the Favipiravir(T–705) and Ribavirin. The results obtained may aid in the designing of new medicine for the treatment and prevention of COVID-19 and other diseases.

Two phase 3 clinical trials showed that use of a monthly vaginal ring containing 25 mg dapivirine was well tolerated and reduced HIV-1 incidence in women by approximately 30% compared with placebo. We aimed to evaluate use and safety of the dapivirine vaginal ring (DVR) in open-label settings with high background rates of HIV-1 infection, an important step for future implementation.

Software reliability growth models are the basic models which predict essential information such as software cost and reliability required for the software development activities. It was assumed that the software behave in the field in the same way as they perform during testing but this assumption may not be true in every situation. In this paper, we discuss such a software reliability growth model which will predict the reliability according to the field environment incorporating two types of S-shaped testing coverage factors. Total expected cost (with warranty and risk cost) and optimal release time for the proposed reliability growth model is proposed. Numerical results using software 'MATLAB' help the software engineers for making their best decision.

Background: Accretion of organic and inorganic contaminants in soil interferes in the food chain, thereby posing a serious threat to the ecosystem and adversely affecting crop productivity and human life. Both endophytic and rhizospheric microbial communities are responsible for the biodegradation of toxic organic compounds and have the capability to enhance the uptake of heavy metals by plants via phytoremediation approaches. The diverse set of metabolic genes encoding for the production of biosurfactants and biofilms, specific enzymes for degrading plant polymers, modification of cell surface hydrophobicity and various detoxification pathways for the organic pollutants, plays a significant role in bacterial driven bioremediation. Various genetic engineering approaches have been demonstrated to modulate the activity of specific microbial species in order to enhance their detoxification potential. Certain rhizospheric bacterial communities are genetically modified to produce specific enzymes that play a role in degrading toxic pollutants. Few studies suggest that the overexpression of extracellular enzymes secreted by plant, fungi or rhizospheric microbes can improve the degradation of specific organic pollutants in the soil. Plants and microbes dwell synergistically, where microbes draw benefit by nutrient acquisition from root exudates whereas they assist in plant growth and survival by producing certain plant growth promoting metabolites, nitrogen fixation, phosphate solubilization, auxin production, siderophore production, and inhibition or suppression of plant pathogens. Thus, the plant-microbe interaction establishes the foundation of the soil nutrient cycle as well as decreases soil toxicity by the removal of harmful pollutants. Conclusion: The perspective of integrating genetic approach with bioremediation is crucial to evaluate connexions among microbial communities, plant communities and ecosystem processes with a focus on improving phytoremediation of contaminated sites.

Tuberculosis (TB) diagnosis in children still remains a challenge in developing countries. We analyze the performance of Xpert MTB/RIF assay for the diagnosis of pediatric TB under programmatic conditions. We retrospectively analyzed the performance of Xpert MTB/RIF assay from February 2016 to March 2018. A total 2678 samples from TB suspects below 14 years were received in the laboratory and were frontline tested by Xpert MTB/RIF assay according to the manufacturer’s instructions. If sample was sufficient, the smear microscopy and culture were performed as per standard World Health Organization’s guidelines. The smears and cultures were performed in 2178 and 588 samples, respectively. Among 2678 samples, 68 were rejected, Xpert MTB/RIF assay was positive in 357/2610 (13.6%) cases, while the smear was positive in 81/2178 (3.3%) cases. The sensitivity of smear and Xpert MTB/RIF when compared with culture was 24.6% (14.1–37.8%) and 81% (68.6–90.1%), respectively. The diagnostic accuracy of Xpert MTB/RIF and smear was 97.1% and 92.2%, respectively. Thirty samples (8.5%) were detected as rifampicin resistance by Xpert MTB/RIF assay. The Xpert MTB/RIF increased the detection rate up to fourfold when compared with smear microscopy. Xpert MTB/RIF assay is the most rapid, sensitive, and specific method for microbiological confirmation and rifampicin resistance detection in pediatric tuberculosis.

Tuberculosis (TB) remains a main hurdle for national programs due to increase in drug resistance to antitubercular drugs. World Health Organization (WHO)-endorsed Line Probe Assay, Genotype MTBDRsl Ver 2.0, gives opportunity for rapid diagnosis and molecular characterization of different mutations in drug targets of fluoroquinolone (FQ) and second-line injectable drugs (SLID). We, retrospectively, analyzed the data of Genotype MTBDRsl Ver 2.0 from January 2018 to June 2018. A total of 863 isolates of Mycobacterium tuberculosis, 687 rifampicin resistant and 176 isoniazid resistant only, were screened for drug resistance in FQ and SLID. All the isolates were tested for Genotype MTBDRsl Ver 2.0 according to the manufacturer’s instructions. The FQ and SLID resistance were detected in 295 (34.2%) and 70 (8.1%) isolates, respectively. Among newly diagnosed and followup rifampicin-resistant TB (RR TB) patients, the FQ resistance was 25.8% and 44.5%, respectively. The most common mutation (42.7%) in FQ-resistant isolates was MUT3C in gyrAgene. Both SLID and FQ resistance were detected in 59 (6.8%) RR TB isolates. The mono SLID resistance was detected in 12 (1.7%) isolates of RR TB. Genotype MTBDRsl Ver 2.0 assay is a rapid and important tool for the diagnosis and molecular characterization of second-line drug resistance under programmatic conditions.

Single agent therapy in the treatment of cancer did not provide satisfactory clinical outcome in a long term due to drug resistance, cumulative toxicity and suboptimal efficacy. Therefore, combination therapies are apt to improve the quality of life in patients. In the present study, combinatorial effect of EPA and/or DHA with doxorubicin (Dox) was evaluated for their potential synergistic effect on human lung adenocarcinoma (A549) cells. The respective IC50values obtained for EPA, DHA and Dox were 170, 140 and 2.5 μmol/L and thus EPA and DHA were separately combined with Dox at constant ratio of 68:1 and 56:1 respectively, depending on the ratio of their IC50values. Different combinations of drugs revealed dose-dependent inhibition of cell viability and IC50values were reduced to nearly 3-fold (58.75 μmol/L) and 4.5-fold (31.5 μmol/L) in EPA-Dox and DHA-Dox combination respectively. Combination index (CI) revealed strong synergism (CI < 0.5) in DHA-Dox (0.49) and moderate synergism (CI > 0.5) in EPA-Dox (0.79) at 0.5 Fa (Fraction affected), which is further confirmed by dose reduction index and isobologram. The mechanisms underlying synergistic interactions involve intracellular ROS generation and MMP depolarisation which causes changes in the cell morphology viz.nuclear fragmentation/condensation, membrane blebbing and early/late apoptotic cells. Moreover, cell cycle arrest was observed at the S and G2/M phase, with more prominent effect in G2/M phase. No toxicity was imposed on non-cancerous HEK-293T cells. These findings suggest that EPA-Dox and DHA-Dox could be explored further for animal studies and clinical trials for lung adenocarcinoma treatment.

Dry eye disease (DED) is one of the most prevalent ocular surface disorders that presents clinically. Recently, the semifluorinated alkane (SFA) perfluorohexyloctane (NovaTears®; EvoTears®) entered the market for the management of evaporative DED, while perfluorobutylpentane has been used as a vehicle to enhance ocular drug delivery. This study evaluated the mechanisms by which SFAs might improve therapeutic outcomes in DED.

Heterogeneous prostatic carcinoma-associated fibroblasts (CAF) contribute to tumor progression and resistance to androgen signaling deprivation therapy (ADT). CAF subjected to extended passaging, compared to low passage CAF, were found to lose tumor expansion potential and heterogeneity. Cell surface endoglin (CD105), known to be expressed on proliferative endothelia and mesenchymal stem cells, was diminished in high passage CAF. RNA-sequencing revealed SFRP1 to be distinctly expressed by tumor-inductive CAF, which was further demonstrated to occur in a CD105-dependent manner. Moreover, ADT resulted in further expansion of the CD105+fibroblastic population and downstream SFRP1 in 3-dimensional cultures and patient-derived xenograft tissues. In patients, CD105+fibroblasts were found to circumscribe epithelia with neuroendocrine differentiation. CAF-derived SFRP1, driven by CD105 signaling, was necessary and sufficient to induce prostate cancer neuroendocrine differentiation in a paracrine manner. A partially humanized CD105 neutralizing antibody, TRC105, inhibited fibroblastic SFRP1 expression and epithelial neuroendocrine differentiation. In a novel synthetic lethality paradigm, we found that simultaneously targeting the epithelia and its microenvironment with ADT and TRC105, respectively, reduced castrate-resistant tumor progression, in a model where either ADT or TRC105 alone had little effect.

Rapid detection of drug resistance in Mycobacterium tuberculosisis important for the successful treatment of tuberculosis. Fluoroquinolone and aminoglycoside resistance detection by molecular methods becomes more complex due to cross resistance among them. Thus, we aimed to determine cross-resistance and mutations in resistance genes for these drugs. A total of 336 multidrug-resistant tuberculosis (MDR-TB) cases received in Mycobacteriology laboratory were screened for phenotypic drug sensitivity testing for second-line drugs, i.e., ofloxacin, amikacin, kanamycin, and capreomycin. Molecular characterization of resistance was done by DNA sequencing of gyrAgene for fuoroquinolones (FQ), and multiplex allele-specific polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (RFLP) of rrsgene for aminoglycosides. Of 336 MDR-TB isolates, 12 were extensively drug-resistant tuberculosis and 219 were sensitive to all the drugs tested. Ofoxacin, amikacin, kanamycin, and capreomycin resistance was detected in 101 (30.1%), 23 (6.8%), 27 (8.1%), and 19 (5.6%) cases, respectively. Eight different mutations were detected in gyrAgene in ofloxacin-resistant isolates and A1401G nucleotide change in rrsgene were seen in 55.6% (15/27), 65.2% (15/23), and 68.4% (13/29) for kanamycin-, amikacin-, and capreomycin-resistant isolates, respectively. Information on second-line drug resistance-associated mutations could potentially be used for development of newer rapid diagnostic tests.

Rising popularity of phytomedicines in various diseased conditions have strengthened the significance of plant-research and evaluation of phytoextracts in clinical manifestations. Pterocarpus marsupium Roxb.,a medicinal plant, known for its anti-oxidant and anti-diabetic activity is a rich source of phytochemicals with antihyperglycemic and antihyperlipidemic activities. However, its possible role in diabetic complications is not evaluated yet. The present study explores the possible role of alcoholic extract of heartwood of P. marsupiumin the treatment of long-term diabetic complications. The alcoholic extract of P. marsupiumwas evaluated for advanced glycation-end-products formation, erythrocyte sorbitol accumulation and rat kidney aldose reductase enzyme inhibition at the concentration of 25–400 μg/ml using in-vitrobioassays. Also the phytoextract at the concentration of 10–320 μg/ml was evaluated for its antioxidant potential by in-vitroantioxidant assays which includes, determination of total phenol content; reducing power assay; nitric oxide scavenging activity; superoxide radical scavenging activity; total antioxidant capacity; total flavonoid content; DPPH scavenging activity; and hydrogen peroxide scavenging activity.

Through this research and client service work, we have developed an in-depth understanding of what SMBs look for from technology providers and how providers can meet those needs more successfully. The smallest companies are even more likely to do so: among companies with fewer than 25 FTEs, 60 percent indicate that they will switch providers in response to any increase in price. What's more, some providers take product bundles for enterprise customers or individual consumers and market them to SMBs with minimal changes. In some technology segments, such as telecom and electronic devices, SMBs spent more than the large-enterprise accounts that providers have historically pursued (Exhibit 1). [Extracted from the article]

Topical drug administration is the preferred route of drug delivery to the eye despite the poor bioavailability. To develop more efficient drug carriers, reliable in vitro or ex vivo models are required in the early stages of formulation development, with such methods being faster, cheaper, and more ethical alternatives to in vivo studies. In vitro cell culture models are increasingly being used for transcorneal penetration studies, with primary cell cultures and immortalized cell lines now giving way to the development of organotypic corneal constructs for studying ocular drug bioavailability. Artificially cultured human corneal equivalents are still in the early stages of development, but present tremendous potential for corneal penetration studies. Ex vivo models using excised animal tissue are also being used to study corneal penetration with promising results, although significant inter-species variations need to be considered. This review discusses the in vitro and ex vivo models currently being used to study corneal penetration and evaluates their advantages and limitations with a focus on diffusion cell assemblies. In addition to the tissue used, the diffusion cell set-up can significantly influence the penetration profile and should be cautiously adjusted to simulate clinical conditions.

Introduction:Deep-learning artificial intelligence (AI) algorithms can identify hypertrophic cardiomyopathy (HCM) from the electrocardiogram (ECG). Preliminary data indicate that AI-ECG may also track treatment response in HCM patients (pts) receiving mavacamten (Mava). In this placebo-controlled analysis, we investigated the performance of AI-ECG in HCM detection and its changes during Mava treatment compared to placebo in the phase 3, EXPLORER-HCM trial.Methods:Pts with non-paced ECGs enrolled in EXPLORER-HCM, evaluating Mava over 30 weeks of treatment, were included. All pts had a 12-lead ECG pre-treatment, at each study visit, and 8 weeks after treatment end. Two independently developed AI-ECG convolutional neural network algorithms from the Mayo Clinic and the University of California, San Francisco (UCSF) were applied to all ECGs suitable for analysis. Serial AI-ECG-predicted scores, which correlate with HCM likelihood (range 0-1), were examined between Mava and placebo groups.Results:A total of 101 Mava and 110 placebo pts were included (mean age 58.6, female 40%). At baseline, the mean Mayo and UCSF AI-ECG scores for HCM were 0.82 and 0.65, with 94% and 88% of pts exceeding the respective diagnostic thresholds of 0.11 (Mayo) and 0.4 (UCSF). During 30 weeks of follow-up in the Mava group, the algorithms showed a mean AI-ECG score reduction of 0.32 (Mayo) and 0.17 (UCSF) in all pts between start and end of treatment. In comparison, AI-ECG scores decreased by 0.05 (Mayo) and increased by 0.02 (UCSF) in the placebo group (Mava vs placebo, t-test p-values <0.001 for both algorithms; Figure)Conclusion:In the EXPLORER-HCM trial population, two independent deep-learning AI-ECG algorithms correctly identified most HCM pts and demonstrated significant reductions in predicted HCM scores after treatment with Mava when compared to placebo. This relative normalization of the ECG suggests disease-modifying properties of Mava, deserving further investigation.

Cleft palate defect with complete edentulism in elderly patients presents a prosthodontic challenge for complete denture fabrication. Such large defects are very difficult to restore by surgical intervention and have direct consequence on such functions as mastication and speech, on aesthetics, and on the patient's mental attitude. This article describes a case report in which a 76-year-old female patient underwent restoration with a closed hollow bulb obturator for a large cleft palate defect.

The article discusses how the students of the Regis School of the Sacred Heart in Houston, Texas reflect God's love by sharing them to their community. It notes that the students of the institution are taught to be compassionately aware of the needs of other people and to be responsive of their needs. According to the author, to be generous and courageous is a way of life for Sacred Heart schools.

Aesthetic dentistry plays a significant role not only in adults but also in pediatric patients. However, a pediatric dentist is faced with the dual problem of satisfying the aesthetic expectations of the patient and parents as well as managing the pediatric patient. In the present era, there are numerous restorative techniques that can be applied to different clinical scenarios. However, we have to choose the technique that best suits our patient, not only biologically but also aesthetically, psychologically, functionally, and financially. The following paper presents the clinical sequence of rehabilitation of severely carious maxillary anterior teeth from left to right lateral incisors in a child with early childhood caries. Severely carious anterior teeth were endodontically treated. The central incisors were restored with gamma loop posts which is mainly used for pediatric patients in endodontically treated teeth. Lateral incisors were treated with Ribbond polyethylene fibre posts. Following this, all the teeth were restored aesthetically with free-hand composite buildup after proper shade selection. The occlusion was restored, and the restorations were finished and polished.