Development, validation and application of single molecule molecular inversion probe based novel integrated genetic screening method for 29 common lysosomal storage disorders in India.

BACKGROUND: Current clinical diagnosis pathway for lysosomal storage disorders (LSDs) involves sequential biochemical enzymatic tests followed by DNA sequencing, which is iterative, has low diagnostic yield and is costly due to overlapping clinical presentations. Here, we describe a novel low-cost and high-throughput sequencing assay using single-molecule molecular inversion probes (smMIPs) to screen for causative single nucleotide variants (SNVs) and copy number variants (CNVs) in genes associated with 29 common LSDs in India. RESULTS: 903 smMIPs were designed to target exon and exon-intron boundaries of targeted genes (n = 23; 53.7 kb of the human genome) and were equimolarly pooled to create a sequencing library. After extensive validation in a cohort of 50 patients, we screened 300 patients with either biochemical diagnosis (n = 187) or clinical suspicion (n = 113) of LSDs. A diagnostic yield of 83.4% was observed in patients with prior biochemical diagnosis of LSD. Furthermore, diagnostic yield of 73.9% (n = 54/73) was observed in patients with high clinical suspicion of LSD in contrast with 2.4% (n = 1/40) in patients with low clinical suspicion of LSD. In addition to detecting SNVs, the assay could detect single and multi-exon copy number variants with high confidence. Critically, Niemann-Pick disease type C and neuronal ceroid lipofuscinosis-6 diseases for which biochemical testing is unavailable, could be diagnosed using our assay. Lastly, we observed a non-inferior performance of the assay in DNA extracted from dried blood spots in comparison with whole blood. CONCLUSION: We developed a flexible and scalable assay to reliably detect genetic causes of 29 common LSDs in India. The assay consolidates the detection of multiple variant types in multiple sample types while having improved diagnostic yield at same or lower cost compared to current clinical paradigm.

Computer-Aided Diagnosis for Leaving Colorectal Polyps In Situ : A Systematic Review and Meta-analysis.

BACKGROUND: Computer-aided diagnosis (CADx) allows prediction of polyp histology during colonoscopy, which may reduce unnecessary removal of nonneoplastic polyps. However, the potential benefits and harms of CADx are still unclear. PURPOSE: To quantify the benefit and harm of using CADx in colonoscopy for the optical diagnosis of small (≤5-mm) rectosigmoid polyps. DATA SOURCES: Medline, Embase, and Scopus were searched for articles published before 22 December 2023. STUDY SELECTION: Histologically verified diagnostic accuracy studies that evaluated the real-time performance of physicians in predicting neoplastic change of small rectosigmoid polyps without or with CADx assistance during colonoscopy. DATA EXTRACTION: The clinical benefit and harm were estimated on the basis of accuracy values of the endoscopist before and after CADx assistance. The certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. The outcome measure for benefit was the proportion of polyps predicted to be nonneoplastic that would avoid removal with the use of CADx. The outcome measure for harm was the proportion of neoplastic polyps that would be not resected and left in situ due to an incorrect diagnosis with the use of CADx. Histology served as the reference standard for both outcomes. DATA SYNTHESIS: Ten studies, including 3620 patients with 4103 small rectosigmoid polyps, were analyzed. The studies that assessed the performance of CADx alone (9 studies; 3237 polyps) showed a sensitivity of 87.3% (95% CI, 79.2% to 92.5%) and specificity of 88.9% (CI, 81.7% to 93.5%) in predicting neoplastic change. In the studies that compared histology prediction performance before versus after CADx assistance (4 studies; 2503 polyps), there was no difference in the proportion of polyps predicted to be nonneoplastic that would avoid removal (55.4% vs. 58.4%; risk ratio [RR], 1.06 [CI, 0.96 to 1.17]; moderate-certainty evidence) or in the proportion of neoplastic polyps that would be erroneously left in situ (8.2% vs. 7.5%; RR, 0.95 [CI, 0.69 to 1.33]; moderate-certainty evidence). LIMITATION: The application of optical diagnosis was only simulated, potentially altering the decision-making process of the operator. CONCLUSION: Computer-aided diagnosis provided no incremental benefit or harm in the management of small rectosigmoid polyps during colonoscopy. PRIMARY FUNDING SOURCE: European Commission. (PROSPERO: CRD42023402197).

Pregnancy-related Factors Responsible for Delivering Low Birth Weight Babies: An Institutional-based Cross-sectional Study, Jamnagar, Gujarat.

Background: The WHO defines LBW as "Birth weight less than 2500 grams" regardless of gestational age. Being born with a low birth weight also incurs enormous economic costs, including higher medical expenditures and social service expenses, and decreased productivity in adulthood. Objective: To study distribution of newborns' according to pregnancy related factors and its association with newborns' birth weight. Methods: An institutional based cross-sectional study. New-borns delivered at study institute were considered as study participants. Estimated final sample size was 500. Guardians (mothers) were face-to-face interviewed and also recorded data were collected from the case file and Mother and Child Protection Card. Results: Prevalence of LBW newborns was higher in mothers with late ANC registration, <4 ANC visits, chronic medical conditions, infection during pregnancy, PIH, anemia, consuming tobacco, exposure to second hand smoke, LSCS/Assisted delivery, in female newborns', current pregnancy birth order number more than 2, in pre term newborns' and mothers with bad obstetric history. Conclusion: Create awareness and adoption of suitable family planning methods. Need to do early (within 12 weeks) ANC registration with minimum four ANC visits for better pregnancy outcome. Effective tracking and suitable intervention provided to improve current pregnancy outcome. Health care professional should pay special attention to high-risk pregnancy. Develop social culture in such a way that females are neither addicted nor exposed to any tobacco containing products in their life.

Effect of a phthalate derivative purified from Bacillus zhangzhouensis SK4 on quorum sensing regulated virulence factors of Pseudomonas aeruginosa.

Pseudomonas aeruginosa causes life-threatening diseases and is resistant to almost all conventional antibiotics. The quorum sensing (QS) system of P. aeruginosa contributes to many pathogenic factors some of which are pigment production, motility, and biofilm. The disruption of quorum sensing system may be an impactful strategy to deal with infections. The present study investigates the anti-quorum sensing property of a bioactive molecule extracted from marine epibiotic bacteria present on the surface of seaweeds. Among all the isolates tested against monitor strain Chromobacterium violaceum (MTCC 2656), the one with the highest activity was identified as Bacillus zhangzhouensis SK4. The culture supernatant was extracted with chloroform which was then partially purified by TLC and column chromatography. The probable anti-QS compound was identified as 1,2-benzenedicarboxylic acid, bis (2-methylpropyl ester) by GC-MS and NMR analysis. The treatment of P. aeruginosa MCC 3457 with the lead compound resulted in the reduced production of pyocyanin, rhamnolipids, exopolysaccharide, biofilm, and motility. The observations of light and scanning electron microscopy also supported the biofilm inhibition. The lead compound showed synergism with the meropenem antibiotic and significantly reduced MIC. The molecular docking and pharmacokinetics study predicted 1, 2-benzenedicarboxylic acid, bis (2-methylpropyl ester), a phthalate derivative as a good drug candidate. The molecular dynamics study was also performed to check the stability of the lead compound and LasR complex. Further, lead compounds did not exhibit any cytotoxicity when tested on human embryonic kidney cells. As per our knowledge, this is the first report on the anti-QS activity of B. zhangzhouensis SK4, indicating that epibiotic bacteria can be a possible source of novel compounds to deal with the multidrug resistance phenomenon.

Nanotechnology-based delivery systems to overcome drug resistance in cancer.

Cancer nanomedicine is defined as the application of nanotechnology and nanomaterials for the formulation of cancer therapeutics that can overcome the impediments and restrictions of traditional chemotherapeutics. Multidrug resistance (MDR) in cancer cells can be defined as a decrease or abrogation in the efficacy of anticancer drugs that have different molecular structures and mechanisms of action and is one of the primary causes of therapeutic failure. There have been successes in the development of cancer nanomedicine to overcome MDR; however, relatively few of these formulations have been approved by the United States Food and Drug Administration for the treatment of cancer. This is primarily due to the paucity of knowledge about nanotechnology and the fundamental biology of cancer cells. Here, we discuss the advances, types of nanomedicines, and the challenges regarding the translation of in vitro to in vivo results and their relevance to effective therapies.

Evaluation of the efficiency of thermostable L-asparaginase from B. licheniformis UDS-5 for acrylamide mitigation during preparation of French fries.

A thermostable L-asparaginase was produced from Bacillus licheniformis UDS-5 (GenBank accession number, OP117154). The production conditions were optimized by the Plackett Burman method, followed by the Box Behnken method, where the enzyme production was enhanced up to fourfold. It secreted L-asparaginase optimally in the medium, pH 7, containing 0.5% (w/v) peptone, 1% (w/v) sodium chloride, 0.15% (w/v) beef extract, 0.15% (w/v) yeast extract, 3% (w/v) L-asparagine at 50 °C for 96 h. The enzyme, with a molecular weight of 85 kDa, was purified by ion exchange chromatography and size exclusion chromatography with better purification fold and percent yield. It displayed optimal catalysis at 70 °C in 20 mM Tris-Cl buffer, pH 8. The purified enzyme also exhibited significant salt tolerance too, making it a suitable candidate for the food application. The L-asparaginase was employed at different doses to evaluate its ability to mitigate acrylamide, while preparing French fries without any prior treatment. The salient attributes of B. licheniformis UDS-5 L-asparaginase, such as greater thermal stability, salt stability and acrylamide reduction in starchy foods, highlights its possible application in the food industry.

Rural/urban disparities in the trends and outcomes of peripartum cardiomyopathy in delivery hospitalizations.

BACKGROUND: Rural-urban disparities in peripartum cardiomyopathy (PPCM) are not well known. We examined rural-urban differences in maternal, fetal, and cardiovascular outcomes in PPCM during delivery hospitalizations. METHODS: We used 2003-2020 data from the National Inpatient Sample for delivery hospitalizations in individuals with PPCM. The 9th and 10th editions of the International Classification of Diseases were used to identify PPCM and cardiovascular, maternal, and fetal outcomes. Rural and urban hospitalizations for PPCM were 1:1 propensity score-matched using relevant clinical and sociodemographic variables. Odds of in-hospital mortality were assessed using logistic regression. RESULTS: Among 72,880 delivery hospitalizations with PPCM, 4,571 occurred in rural locations, while 68,309 occurred in urban locations. After propensity matching, there were a total of 4,571 rural-urban pairs. There was significantly higher in-hospital mortality in urban compared to rural hospitalizations (adjusted OR 1.54, 95% CI 1.10-1.89). Urban PPCM hospitalizations had significantly higher cardiogenic shock (2.9% vs. 1.3%), mechanical circulatory support (1.0% vs. 0.6%), cardiac arrest (2.3% vs. 0.9%), and VT/VF (4.5% vs. 2.1%, all p <.05). Additionally, urban PPCM hospitalizations had worse maternal and fetal outcomes as compared to rural hospitalizations, including higher preterm delivery, gestational diabetes, and fetal death (all p<.05). Notably, significantly more rural individuals were transferred to a short-term hospital (including tertiary care centers) compared to urban individuals (13.5% vs. 3.2%, p<.0001). CONCLUSIONS: There are significant rural-urban disparities in delivery hospitalizations with PPCM. Worse outcomes were associated with urban hospitalizations, while rural PPCM hospitalizations were associated with increased transfers, suggesting inadequate resources and advanced sickness.

Dietary Practices Among Type 2 Diabetes Patients Visiting a Non-communicable Disease (NCD) Clinic in a District of Western India: A Cross-Sectional Study.

BACKGROUND AND AIMS: Diabetes is becoming a major public health problem in the country. One of the most important lifestyle modifications necessary for diabetic patients is maintaining healthy dietary choices. These modifications in dietary practices are supposed to be followed lifelong, along with medication, for better glycemic control. Despite understanding the importance of dietary control and physical activity in the management of diabetes, adherence to these practices is poor. This study aimed to assess the dietary practices of type 2 diabetes mellitus (T2DM) patients and various factors that determine adherence to these healthy dietary practices. The secondary objective was to find the perceptions of participants about the role of diet in controlling diabetes and to find the perception-practice gap among study participants. METHODOLOGY: It was a hospital-based cross-sectional study conducted among 450 T2DM patients visiting the non-communicable disease (NCD) clinics of tertiary care hospitals and community health centres (CHCs) of the study district. Dietary practice was assessed using a modified UK Diabetes and Diet Questionnaire (UKDDQ), considering the food patterns in the study area. Statistical tests like chi-square and ordinal logistic regression were applied using Jamovi software for univariate and multivariate analyses. RESULTS: The healthiest food choices were abstinence from alcohol consumption (100%), avoiding processed meat (92.21%), high-fibre breakfast (70.4%), and daily consumption of vegetables (68.2%). Improper dietary practices were regular sugary drinks (38%) and high-glycemic-index food items (22.4%). The mean (SD) of the composite score was 68.02 (8.7) and the median score (interquartile range (IQR)) was 69 (60-76). Tertile analysis of the composite score revealed that with the increase in age, patients were less likely to be in the intermediate or upper tertile score (ß = -0.0219, p = 0.016). Being female (odds ratio (OR) =0.603, CI: 0.395-0.917, p = 0.019) and living in a three-generation family made the patients less likely to be in the upper tertile score. CONCLUSION: Nearly half of the participants had an overall healthy score. Dietary practices were healthy among the participants of lower ages, males, and those living in nuclear and joint families. The highest perception-practice gap was seen for fruit and rice consumption.

Meglumine-based Sustainable Three-component Deep Eutectic Solvent Applicable for the Synthesis of Pyrazolo[5,1-b]quinazoline-3-carboxylates as a Sensing Probe for Cu2+ Ions.

An unprecedented meglumine-based three-component deep eutectic solvent (3c-DES) (MegPAc) was synthesized using meglumine, p-toluenesulfonic acid (PTSA), and acetic acid as a renewable, and non-toxic solvent. The exploitation of the MegPAc as an eco-friendly reaction media to construct a selective and sensitive small organic molecular sensing probe, namely, pyrazolo[5,1-b]quinazoline-3-carboxylates (PQCs) was executed. Captivatingly, the MegPAc served the dual role of solvent and catalyst, and it delivered the title components with 69-94 % yields within 67-150 minutes. Furthermore, a UV-visible study unfolds the selective detection of Cu2+ ions with our synthetic probe 4 ba and resulted in hypsochromic shift due to electrostatic interactions. Additionally, 1H NMR titration study and density functional theory (DFT) calculations were performed to attest the binding mechanism of sensing probe 4 ba and Cu2+ ions. Worthy of mention, this protocol unveils the efficacy of meglumine-based 3c-DES for the first time as a bio-renewable system to synthesize the PQCs.

Therapeutic evolution in HR+/HER2- breast cancer: from targeted therapy to endocrine therapy.

Breast cancer, a complex and varied disease, has four distinct subtypes based on estrogen receptor and human epidermal growth factor receptor 2 (HER2) levels, among which a significant subtype known as HR+/HER2-breast cancer that has spurred numerous research. The prevalence of breast cancer and breast cancer-related death are the most serious threats to women's health worldwide. Current progress in treatment strategies for HR+/HER2-breast cancer encompasses targeted therapy, endocrine therapy, genomic immunotherapy, and supplementing traditional methods like surgical resection and radiotherapy. This review article summarizes the current epidemiology of HR+/HER2-breast cancer, introduces the classification of HR+/HER2-breast cancer and the commonly used treatment methods. The mechanisms of action of various drugs, including targeted therapy drugs and endocrine hormone therapy drugs, and their potential synergistic effects are deeply discussed. In addition, clinical trials of these drugs that have been completed or are still in progress are included.

Medication-overuse headache overlapping with serotonin syndrome.

Serotonin syndrome (SS) is an iatrogenic, drug-induced clinical syndrome caused by an increase in the intrasynaptic concentration of serotonin. Serotonin plays a significant role in the pathophysiology of migraines. Upregulation of 5-HT2A receptors is found in medication-overuse headache (MOH). Several migraine medications, both preventative and abortive drugs, act on serotonin receptors. We report two patients with chronic migraine who developed MOH. Besides headache, patients had frequent attacks of dizziness, restlessness, irritability, insomnia, excessive sweating, abdominal discomforts and tremors. These symptoms were suggestive of withdrawal headache. However, on physical examinations, we elicited hyperreflexia, hypertonia, clonus, tachycardia, hypertension, mydriasis and hyperactive bowel sound. Both patients also met the criteria for SS. Cyproheptadine was started. All features, including headaches, got better after cyproheptadine administration within 24 hours. In 7 days, there was practically total improvement. Both patients continued to take cyproheptadine as a preventative medicine, and migraine frequency was under control.

Chronic dizziness in restless legs syndrome (RLS) patients responsive to levodopa or dopamine agonists.

Apart from the legs, restless legs syndrome (RLS) also affects the arms, head, neck, face, oral cavity, genital area, abdomen, intestines and bladder. RLS is also linked to several comorbid diseases, including headache disorders. Its association with dizziness has never been explored. We are reporting on two patients with RLS who also had a history of chronic dizziness. The treatment with levodopa or dopamine agonists completely alleviated both RLS and dizziness. We propose that RLS-like symptoms in the head may be experienced as dizziness and that dizziness may be part of the symptom complex of RLS. A large number of patients with chronic dizziness remain undiagnosed in clinical practice. We suggest exploring the history of RLS in patients presenting with chronic dizziness. Such patients may respond to levodopa or dopamine agonists. Because the response was seen in only two patients, a prospective placebo-controlled trial is needed to confirm these findings.

Analyzing methods for reducing recurrence rates after EMR of large nonpedunculated colorectal polyps: an indirect pairwise comparison.

BACKGROUND AND AIMS: Despite advances in EMR techniques, a high polyp recurrence rate remains a challenge. Due to the scarcity of direct comparisons, we performed an indirect comparison of conventional EMR (EMR alone), underwater EMR (U-EMR), and EMR + adjuvant thermal ablation of polypectomy margins to assess polyp recurrence rates. METHODS: Electronic databases were searched from inception to January 12, 2023, for studies reporting polyp recurrence rates after EMR for large nonpedunculated polyps (>15 mm) with or without adjuvant techniques (snare tip soft coagulation [STSC]/argon plasma coagulation [APC]). An indirect comparison was performed by using the frequentist method. The p-score was calculated to identify preferred intervention. Publication bias was assessed by using a comparison-adjusted funnel plot. RESULTS: A total of 9 full articles were identified. On direct comparisons, EMR + STSC had 82% reduced odds (odds ratio, .18; 95% confidence interval, .13-.26; P < .001), whereas U-EMR alone had 77% reduced odds (odds ratio, .23; 95% confidence interval, .08-.67; P = .007) of polyp recurrence compared with EMR alone. On indirect comparison, all interventions had significantly lower odds of polyp recurrence compared with EMR alone. The p-score ranking showed that EMR + STSC seems a potential first method in reducing the odds of polyp recurrence, followed by U-EMR, EMR + APC, and EMR alone. CONCLUSIONS: EMR + STSC seems to provide favorable odds for reducing polyp recurrence postresection for large nonpedunculated polyps. Standardization of methods to detect residual polyp and prevent polyp recurrence at the time of EMR are required.

Dizziness and vertigo in patients with tension-type headache: A case-control study.

BACKGROUND: A few studies have demonstrated dizziness and vertigo in patients with tension-type headache (TTH). However, the prevalence and other characteristics of vestibular symptoms in TTH has not been studied in a systemic manner so far. The aim of the study was to see the prevalence of vestibular symptoms in patients with tension-type headache as compared with controls. METHODS: This case-control study included 100 TTH patients and 100 controls who do not have significant history of headaches. RESULTS: Vestibular symptoms (Vertigo, dizziness, vestibulovisual or postural symptom) were experienced by 25% of patients with TTH and 10% in the control group (Odd Ratio = 3.0 [95% CI, 1.4-6.6], P = .006). The vestibular symptoms were statistically more in patients with chronic tension-type headache (CTTH) than episodic TTH (67% vs 9%. 9, P5 = < 0.005). Hospital Anxiety and Depression score (HAD-A and HAD-D) scores in patients with TTH with vestibular symptoms were significantly higher than TTH without vestibular symptoms- HAD-A (5.1 ± 1.7 vs 4.0 ± 1.5, P = 0.002) and HAD-D(5.8 ± 2.1 vs 4.2 ± 1.9, P = < 0.001). Phonophobia was also more frequent in TTH patients with vertigo (42% vs.13%, P5 = 0.005). CONCLUSION: Vestibular symptoms may be more common in patients TTH than control. The prevalence of vestibular symptoms depends on the frequency of TTH.

Intraoperative navigation system use increases accuracy of glenoid component inclination but not functional outcomes in reverse total shoulder arthroplasty: a prospective comparative study.

BACKGROUND: While the use of computer-assisted navigation systems in prosthetic implantation is steadily increasing, its utility in reverse shoulder arthroplasty (RSA) remains unclear. The purpose of this study was to evaluate the clinical utility of an intraoperative navigation system in patients undergoing RSA. MATERIALS AND METHODS: Patients undergoing navigated or standard RSA at a single institution between September 2020 and December 2021 were prospectively enrolled. Exclusion criteria included noncompliance with study procedures or humeral fracture. Outcome measures included postoperative version and inclination, range of motion (ROM), complications, and patient-reported outcome measurements (PROMs: American Shoulder and Elbow Surgeons score [ASES], Disabilities of the Arm, Shoulder, and Hand score [DASH], Simple Shoulder Test [SST], and Visual Analog Scale [VAS]) at final follow-up. RESULTS: The final cohort contained 16 patients with navigation and 17 with standard RSA at a mean follow-up of 16 months (range 12-18 months). Average age was 72 years (range 66-80 years), 8 male (24%) and 25 female (76%). There were no differences in demographics between groups (p > 0.05). At baseline, the navigated group had a greater proportion of Walch B1 and B2 glenoids (p = 0.04). There were no differences between groups regarding baseplate type and native/planned/postoperative glenoid version and inclination. In both groups, planned and postoperative versions were not significantly different (p = 0.76). Patients who did not have navigation demonstrated significant differences between planned and postoperative inclination (p = 0.04), while those with navigation did not (p = 0.09). PROM scores did not differ between groups at final follow-up for SST (p = 0.64), DASH (p = 0.38), ASES (p = 0.77), or VAS (p = 0.1). No difference in final ROM was found between groups (p > 0.05). Over 50% of all screws in both groups were positioned outside the second cortex (p = 0.37), albeit with no complications. CONCLUSIONS: There were no statistically significant differences in ROM, PROMs, and satisfaction between patients receiving computer-navigated and standard RSA at a short-term follow-up. Despite more severe preoperative glenoid erosion in the navigated group, all patients were able to achieve an appropriate neutral axis postoperatively. The cost effectiveness and appropriate use of computer-navigated RSA warrant specific investigation in future studies. LEVEL OF EVIDENCE: II, prospective cohort study. TRIAL REGISTRATION: 9/1/2020 to 12/31/2021.

Using landfill leachate to indicate the chemical and biochemical activities in elevated temperature landfills.

Landfill leachate properties contain important information and can be a unique indicator for the chemical and biochemical activities in landfills. In the recent decade, more landfills are experiencing elevated temperature, causing an imbalance in the decomposition of solid waste and affecting the properties of the landfill leachate. This study analyzes the properties of leachate from two landfills that were experiencing elevated temperature (ETLFs), samples were collected from both elevated temperature impacted and non-impacted areas in each landfill. The accumulation of volatile fatty acids (VFA) in leachates from elevated temperature impacted areas of both landfill sites revealed that methanogenesis was inhibited by the elevated temperature, which was further confirmed by the more acidic pH, higher H/C elemental ratio, and lower degree of aromaticity of the elevated temperature impacted leachates. Also, carbohydrates depletion indicated possible enhancement of hydrolysis and acidogenesis by elevated temperature, which was supported by compositional comparison of isolated acidic species by negative-ion electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICRMS) at 21 T derived from both elevated temperature impacted and non-impacted areas in the same landfill site. Furthermore, leachate organics fractionation showed that leachates not impacted by elevated temperature contain less hydrophilic fraction and more humic fraction than elevated temperature-impacted leachates for both ETLFs.

When online citizen science meets teaching: Storyfication of a science discovery game to teach, learn, and contribute to genomic research.

In the last decade, video games became a common vehicle for citizen science initiatives in life science, allowing participants to contribute to real scientific data analysis while learning about it. Since 2010, our scientific discovery game (SDG) Phylo enlists participants in comparative genomic data analysis. It is frequently used as a learning tool, but the activities were difficult to aggregate to build a coherent teaching activity. Here, we describe a strategy and series of recipes to facilitate the integration of SDGs in courses and implement this approach in Phylo. We developed new roles and functionalities enabling instructors to create assignments and monitor the progress of students. A story mode progressively introduces comparative genomics concepts, allowing users to learn and contribute to the analysis of real genomic sequences. Preliminary results from a user study suggest this framework may help to boost user motivation and clarify pedagogical objectives.

Microwave-induced one-pot synthesis of 3-imidazolyl indole clubbed 1,2,3-triazole hybrids as antiproliferative agents and density functional theory study.

Herein, we outline a highly efficient PEG-4000-mediated one-pot three-component reaction for the synthesis of 3-imidazolyl indole clubbed 1,2,3-triazole derivatives (5a-r) at up to 96% yield as antiproliferative agents. This three-component protocol offers the advantages of an environmentally benign reaction, excellent yield, quick response time, and operational simplicity triggered by the copper catalyst under microwave irradiation. All the synthesized compounds were tested for antiproliferative activity against six human solid tumor cell lines, that is, A549 and SW1573 (nonsmall cell lung), HBL100 and T-47D (breast), HeLa (cervix), and WiDr (colon). Among them, six compounds, 5g-j, 5m, and 5p, demonstrated effective antiproliferative action with GI50 values under 10 µM. Furthermore, density functional theory (DFT) calculations were performed for all the synthesized molecules through geometry optimizations, frontier molecular orbital approach, and molecular electrostatic potential (MESP). The theoretical DFT calculation was performed using the DFT/B3LYP/6-31+G (d,p) basis set. Moreover, the biological reactivity of all the representative synthesized molecules was compared with the theoretically calculated quantum chemical descriptors and MESP 3D plots. We also investigated the drug-likeness characteristic and absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction. In general, our approach enables environmentally friendly access to 3-imidazolyl indole clubbed 1,2,3-triazole derivatives as prospective antiproliferative agents.