The advent of the fourth industrial revolution, characterized by artificial intelligence (AI) as its central component, has resulted in the mechanization of numerous previously labor-intensive ...activities. The use of in silico tools has become prevalent in the design of biopharmaceuticals. Upon conducting a comprehensive analysis of the genomes of many organisms, it has been discovered that their tissues can generate specific peptides that confer protection against certain diseases. This study aims to identify a selected group of neuropeptides (NPs) possessing favorable characteristics that render them ideal for production as neurological biopharmaceuticals. Until now, the construction of NP classifiers has been the primary focus, neglecting to optimize these characteristics. Therefore, in this study, the task of creating ideal NPs has been formulated as a multi-objective optimization problem. The proposed framework, NPpred, comprises two distinct components: NSGA-NeuroPred and BERT-NeuroPred. The former employs the NSGA-II algorithm to explore and change a population of NPs, while the latter is an interpretable deep learning-based model. The utilization of explainable AI and motifs has led to the proposal of two novel operators, namely p-crossover and p-mutation. An online application has been deployed at https://neuropred.anvil.app for designing an ideal collection of synthesizable NPs from protein sequences.
Artificial intelligence (AI) systems are trained to solve complex problems and learn to perform specific tasks by using large volumes of data, such as prediction, classification, recognition, ...decision-making, etc. In the past three decades, AI research has focused mostly on the model-centric approach compared to the data-centric approach. In the model-centric approach, the focus is to improve the code or model architecture to enhance performance, whereas in data-centric AI, the focus is to improve the dataset to enhance performance. Data is food for AI. As a result, there has been a recent push in the AI community toward data-centric AI from model-centric AI. This paper provides a comprehensive and critical analysis of the current state of research in data-centric AI, presenting insights into the latest developments in this rapidly evolving field. By emphasizing the importance of data in AI, the paper identifies the key challenges and opportunities that must be addressed to improve the effectiveness of AI systems. Finally, this paper gives some recommendations for research opportunities in data-centric AI.
A BSTRACT Rhabdomyosarcoma (RMS) is the most common soft tissue tumor in children and is rarely seen in adults. It is slightly more common in females. It constitutes <1% of all breast malignancies. ...Radiologically, it is difficult to differentiate RMS from other breast benign or malignant tumors. Hence, it is often diagnosed late. Immunohistochemistry staining with actin, desmin, myogenin, and myoD1 confirms the diagnosis. There is no standard treatment due to rarity of cases. Role of radiotherapy is still controversial, but many studies have shown the benefit of radiotherapy in large tumors of more than 5 cm. RMSs are usually aggressive tumors with survival ranging from 3 months to 7 years. Here, we report a case of primary RMS of the breast in a 49-year-old female, describing radiological and pathological features and treatment with volumetric modulated arc technique radiotherapy.
A simple RP-HPLC method for the quantification of valsartan (VAL), amlodipine (AML) and hydrochlorothiazide (HCT) in human plasma was developed and validated. VAL, AML and HCT were resolved using a ...Gemini C18 column and mobile phase gradient starting from 20 % acetonitrile and 80 % 10 mmol L-1 ammonium formate (V/V, pH 3.5 ± 0.2, by formic acid) to 70 % acetonitrile and 30 % 10 mmol L-1 ammonium formate, over 20 minutes, with a flow rate of 1 mL min-1. The samples were purified by protein precipitation and extraction. Telmisartan was used as internal standard. The method was validated according to USFDA and EMEA guidelines with good reproducibility and linear responses R = 0.9985 (VAL), 0.9964 (AML), and 0.9971 (HCT). RSDs of intra- and inter-day precision ranged 2.2-8.1 and 4.6-11.7 %, respectively, for all three drugs. Mean extraction recoveries of three QCs for the triple drug combination were 76.5 (VAL), 72.0 (AML) and 73.0 (HCT) % for human plasma. Although the LC-MS/MS method is more sensitive than HPLC, HPLC is still suitable for preliminary pharmacokinetic study. The experiments performed demostrated that simultaneous determination of all components of the triple drug combination in human plasma can be done by this method. Proposed method can be also used for guidance to the LC-MS/MS method.
U ovom radu opisana je i validirana jednostavna RP-HPLC metoda za određivanje valsartana (VAL), amlodipina (AML) i hidroklorotiazida (HCT) u humanoj plazmi. VAL, AML i HCT su razlučeni na koloni Gemini C18. Početni sastav mobilne faze bio je acetonitril (20 %) i 10 mmol L-1 otopina amonijevog formijata (80 %, V/V, pH podešen na 3,5 ± 0,2 pomoću mravlje kiseline), a nakon 20 minuta 70 % acetonitrila i 30 % 10 mmol L-1 amonijevog formijata, uz protok od 1 mL min-1. Uzorci su pročišćeni taloženjem proteina i ekstrakcijom. Telmisartan je upotrebljen kao unutarnji standard. Metoda je validirana prema uputama USFDA i EMEA uz dobro reproducibilnost i linearnost: R = 0.9985 (VAL), 0.9964 (AML), and 0.9971 (HCT). Ponovljivost i intermedijarna preciznost bile su u rasponu 2,2-8,1, odnosno 4,6-11,7 % za sve tri ljekovite tvari. Srednji povrat ekstrakcije iz humane plazme za ovu kombinaciju lijekova iznosila je 76,5 (VAL), 72,0 (AML) i 73,0 (HCT) %. Iako je LC-MS/MS metoda osjetljivija od HPLC metode, HPLC je prihvatljiva za preliminarna farmakokinetička ispitivanja. Provedeni pokusi pokazuju da se predlož enom metodom mogu simultano odrediti sastavnice trostruke kombinacije lijekova u humanoj plazmi. Predložena metoda može biti korisna smjernica za LC-MS/MS metodu.
A series of novel 4-Benzyl-1,3-thiazole derivatives was synthesized by applying analogue-based drug design approach and they were screened for anti-inflammatory activity. Darbufelone (CI 1004) a dual ...COX/LOX inhibitor, served as a lead molecule for designing a molecular scaffold. The derivatives with the 1,3 thiazole molecular scaffold bearing a side chain at position-2 resembling that of Romazarit (Ro-31-3948) were synthesized. The substitution at the second position of thiazole scaffold consisted of either carbalkoxy amino or aryl amino side chain. The introduction of an NH linker at the second position was the bioisoteric approach to impart the metabolic stability to the carbalkoxy side chains in designed molecules so as to avoid the likelihood of generating toxic moieties, like in Romazarit, which was withdrawn due to its toxicity profile. An important outcome of this study is the optimization of the substitution at the second position of the thiazole scaffold in eliciting better biological activity. The biological activity exhibited by the two designed series were in the order of carbalkoxy amino series > phenyl amino series. Molecule RS31 had emerged to be best compound in the whole series, having the side chain -NH-(C = O)O-R which resemble to Romazerit with 1,3 thiazole scaffold and substituted phenyl carbonyl group at fifth position derived from the retro-analysis of Darbufelone. This novel three-point pharmacophore, which is necessarily evolved from a lead-based drug design strategy, has opened up new avenues in designing of molecules acting on more than one rate-limiting step along the inflammatory cascade.
Machine learning (ML) has become a popular technique for various automation tasks in the era of Industry 4.0, such as the analysis and synthesis of visual data such as images and videos, natural ...language and speech, financial data, and biomedical applications. However, ML-based automation techniques are facing difficulties like decision-making, thus incorporating user expertise into the system might be advantageous. The goal of adding human domain expertise with ML-based automation is to provide more accurate prediction models. Human-in-the-loop (HITL) systems that integrate human expertise with ML algorithms are becoming more and more common in various industries. However, there are a number of methodological, technical, and ethical difficulties with the development and application of HITL systems. This paper aims to explore the methodologies, challenges, and opportunities associated with HITL systems implementations. We also discuss a number of issues that must be resolved for HITL systems to be effective, including data quality, bias, and user engagement. Besides, we also explored several approaches that can be utilized to enhance the performance of HITL systems, such as active learning (AL), iterative ML, and reinforcement learning, as well as the current state of the art in HITL systems. We also selectively highlighted the advantages of HITL systems, such as their potential to increase decision-making process accountability and transparency by utilizing human experience to improve ML decision-making capability. The paper will be very useful for researchers, practitioners, and policymakers.
Extramedullary plasmacytomas (EMPs) are solitary plasma cell neoplasms that involve sites other than bone or bone marrow. It constitutes only 0.4% of tumors of head-and-neck region. Surgery and ...radiotherapy are standard treatment, depending on the site. Radiotherapy promises 90-100% local control rate and prolonged survival. Here, we are reporting a case of plasmacytoma nasopharynx treated with volumetric-modulated arc technique (VMAT) radiotherapy, with contouring details, dose to target, and nearby structures. Patient had complete response and is relapse free for the past 3 years with minimal toxicity. In our case, the lesion is in nasopharynx and is about 1cm, as such it required precise radiotherapy technique like VMAT, to give targeted dose delivery and sparing the nearby critical organs.
Mantle cell lymphoma (MCL) or mature peripheral B-cell lymphoid neoplasm is a type of non-Hodgkin's lymphoma. It is more common in elderly males. It is very rare, accounting for less than 1% of head ...and neck malignancies. MCL is usually positive for CD20, CD5, CD43, cyclin D1 and negative for CD10, CD23, and BCL6. It is a very aggressive neoplasm, and hence, patients often present in advanced stage. Due to its rare incidence and short clinical course, there are limited data on standard treatment protocols. Even with the present treatment protocols, only 30% of patients achieve complete response. Here, we present a case of synchronous presentation of MCL of the nasopharynx and larynx in a 69-year-old male. We aim to discuss the investigations and treatment done with volumetric modulated arc technique radiotherapy that led to complete response.
•Nutritional impact of frying herb/spice-infused rice crackers has been evaluated.•Mint incorporated rice crackers had higher fibre and minerals than other crackers.•Total polyphenol content of raw ...and fried mint cracker was high among others.•Phenolic compounds, minerals, and pigments of cracker are leached into fried oil.•Direct inclusion of spice/herbs pigments to rice crackers may be lost after frying.
Herbs and spices are rich in bioactive compounds that are known to impart health benefits. Incorporation of these herbs/spices in snacks might also enhance the nutritional quality of the products. This study aimed to examine the potential nutritional benefits and loss associated with the frying of herb/spice rice crackers. Four different varieties of rice-based crackers incorporated individually with mint, green chili, red chili, and cumin were evaluated by different parameters before and after frying. The raw rice cracker incorporated with herb/spice exhibited significantly higher protein (4.19 to 5.30 %), fiber (1.78 to 1.97 %), mineral, pigment (chlorophyl 0.4 to 0.7 mg% and carotenoids 150 to 400 mg/kg), phenolic content (2.81 to 9.18 mg GAE/g), and antioxidant capacity than the control raw rice cracker (without herb/spice). The frying treatment was found to have a reduction in the nutritional value i.e., protein (3.30 to 3.82%), fiber (1.47 to 1.86), mineral and pigment content of rice crackers. Moreover, the increase in phenolic content, mineral, antioxidant capacity, and pigments of cooking oil in which rice crackers were fried confirmed the leaching of herbs/spices into the oil while frying.
Basmati is a speciality segment in the rice genepool characterised by explicit grain quality. For the want of suitable populations, genome-wide association study (GWAS) in Basmati rice has not been ...attempted.
To address this gap, we have performed a GWAS on a panel of 172 elite Basmati multiparent population comprising of potential restorers and maintainers. Phenotypic data was generated for various agronomic and grain quality traits across seven different environments during two consecutive crop seasons. Based on the observed phenotypic variation, three agronomic traits namely, days to fifty per cent flowering, plant height and panicle length, and three grain quality traits namely, kernel length before cooking, length breadth ratio and kernel length after cooking were subjected to GWAS. Genotyped with 80K SNP array, the population was subjected to principal component analysis to stratify the underlying substructure and subjected to the association analysis using Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) model.
We identified 32 unique MTAs including 11 robust MTAs for the agronomic traits and 25 unique MTAs including two robust MTAs for the grain quality traits. Six out of 13 robust MTAs were novel. By genome annotation, six candidate genes associated with the robust MTAs were identified. Further analysis of the allelic combinations of the robust MTAs enabled the identification of superior allelic combinations in the population. This information was utilized in selecting 77 elite Basmati rice genotypes from the panel.
This is the first ever GWAS study in Basmati rice which could generate valuable information usable for further breeding through marker assisted selection, including enhancing of heterosis.
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