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1.
J Sci Food Agric ; 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38629581

ABSTRACT

BACKGROUND: Sugarcane juice, which has a short shelf life, is a popular thirst-quenching and rejuvenating beverage worldwide. The limited shelf life is a result of changes in polyphenol oxidase (PPO) activity, total plate count (TPC) and color attributes (L*, a* and b*-values). We hypothesized that chemical kinetics and thermodynamics of blanched sugarcane cane juice causing alterations in PPO, TPC, and L, a* and b*-values will address the challenges of sugarcane juice preservation. RESULTS: Sugarcane billets were blanched at variable time-temperature combinations in the range 0-20 min and 70-90 °C. Reaction rates increased with increasing temperature; PPO activity, TPC and colour followed first-order kinetics. PPO activity had an activation energy (Ea) of 81 kJ mol-1. The half life (t½) dropped from 16.5 to 3.47 min and decimal reduction time (D-values) dropped from 54.83 to 11.52 min. Thus reactions were temperature-sensitive. Thermodynamic studies indicated an endothermic (positive enthalpy values, ΔH > 0; 78.10 kJ mol-1) and reversible process (negative entropy values ΔS < 0; -0.044 kJmol-1 K-1). Michaeli-Menten constant (Km) and maximum velocity (Vmax) of PPO activity were determined by adding variable lemon juice concentrations in sugarcane juice. As the Km values increased (from 5.53 to 15.81 mm) and Vmax values decreased (from 666.67 to 384.61 UmL-1), a Lineweaver-Burk plot suggested decreased PPO affinity of sugarcane juice. CONCLUSION: The results of the present study indicate that studies on chemical kinetics and thermodynamics (PPO, TPC and L, a* and b*-values) of blanched sugarcane cane juice shall mitigate challenges of sugarcane juice preservation. © 2024 Society of Chemical Industry.

2.
Cureus ; 16(3): e56925, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38665756

ABSTRACT

BACKGROUND: E-classrooms help teachers save time, keep classes organized, and improve communication with students. This study aims to assess Google Classroom's usefulness in enhancing medical students' knowledge and acceptance of new technology for in-depth learning. MATERIAL AND METHOD: This educational interventional study was carried out on 100 students in the 3rd year of the M.B.B.S., Part 1. After a briefing about Google Classroom and educational topics, enrolled students and faculty were allowed to discuss the topic for two months. Following this, the descriptive approach was utilized to describe the respondents' technology acceptance through the administration of the technology acceptance model (TAM) survey questionnaire. RESULTS: Students were actively involved in discussion, with a 67% response rate. Nearly 85% of students agreed that Google Classroom is a satisfactory way for in-depth knowledge acquisition. On factor analysis, it was observed that the goodness of fit was 0.985, suggesting that the model is acceptable. It was also found that perceived usefulness (PU) had a significant positive effect on motivation towards self-directed learning (SDL), and perceived ease of use (PEOU) had a positive effect on both behavioural intention and actual use. CONCLUSION: Google Classroom is a valuable tool for learning that can enhance active self-learning and increase behavioural intention and actual use. It should be incorporated into day-to-day teaching activities to overcome time constraints.

3.
Heliyon ; 10(6): e27947, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38509880

ABSTRACT

Cerebral small vessel disease (SVD) may be associated with an increased risk of depressive symptoms. Serum uric acid (SUA), an antioxidant, may be involved in the occurrence and development of depressive symptoms, but the mechanism remains unknown. Moreover, the relationship between structural brain networks and SUA has not been explored. This study examined the relationship between SUA and depressive symptoms in patients with SVD using graph theory analysis. We recruited 208 SVD inpatients and collected fasting blood samples upon admission. Depressive symptoms were assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24). Magnetic resonance imaging was used to evaluate SVD, and diffusion tensor images were used to analyze structural brain networks using graph theory. Patients with depressive symptoms (n = 34, 25.76%) compared to those without (334.53 vs 381.28 µmol/L, p = 0.017) had lower SUA levels. Graph theoretical analyses showed a positive association of SUA with betweenness centrality, nodal efficiency, and clustering coefficients and a negative correlation with the shortest path length in SVD with depressive symptoms group. HAMD scores were significantly associated with nodal network metrics in the right cerebral hemisphere. Our findings suggested that lower SUA levels are significantly associated with disrupted structural brain networks in the right cerebral hemisphere of patients with SVD who have depressive symptoms.

4.
J Clin Invest ; 134(8)2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38421735

ABSTRACT

RAD54 and BLM helicase play pivotal roles during homologous recombination repair (HRR) to ensure genome maintenance. BLM amino acids (aa 181-212) interact with RAD54 and enhance its chromatin remodeling activity. Functionally, this interaction heightens HRR, leading to a decrease in residual DNA damage in colon cancer cells. This contributes to chemoresistance in colon cancer cells against cisplatin, camptothecin, and oxaliplatin, eventually promoting tumorigenesis in preclinical colon cancer mouse models. ChIP-Seq analysis and validation revealed increased BLM and RAD54 corecruitment on the MRP2 promoter in camptothecin-resistant colon cancer cells, leading to BLM-dependent enhancement of RAD54-mediated chromatin remodeling. We screened the Prestwick small-molecule library, with the intent to revert camptothecin- and oxaliplatin-induced chemoresistance by disrupting the RAD54-BLM interaction. Three FDA/European Medicines Agency-approved candidates were identified that could disrupt this interaction. These drugs bound to RAD54, altered its conformation, and abrogated RAD54-BLM-dependent chromatin remodeling on G5E4 and MRP2 arrays. Notably, the small molecules also reduced HRR efficiency in resistant lines, diminished anchorage-independent growth, and hampered the proliferation of tumors generated using camptothecin- and oxaliplatin-resistant colon cancer cells in both xenograft and syngeneic mouse models in BLM-dependent manner. Therefore, the 3 identified small molecules can serve as possible viable candidates for adjunct therapy in colon cancer treatment.


Subject(s)
Colonic Neoplasms , Drug Resistance, Neoplasm , Humans , Animals , Mice , Oxaliplatin/pharmacology , DNA Repair , Camptothecin , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Cell Proliferation
5.
J Alzheimers Dis ; 97(4): 1727-1735, 2024.
Article in English | MEDLINE | ID: mdl-38306040

ABSTRACT

Background: Mild behavioral impairment (MBI) is one of the earliest observable changes when a person experiences cognitive decline and could be an early manifestation of underlying Alzheimer's disease neuropathology. Limited attention has been given to investigating the clinical applicability of behavioral biomarkers for detection of prodromal dementia. Objective: This study compared the prevalence of self-reported MBI and vascular risk factors in Southeast Asian adults to identify early indicators of cognitive impairment and dementia. Methods: This cohort study utilized baseline data from the Biomarkers and Cognition Study, Singapore (BIOCIS). 607 participants were recruited and classified into three groups: cognitively normal (CN), subjective cognitive decline (SCD), and mild cognitive impairment (MCI). Group comparisons of cognitive-behavioral, neuroimaging, and blood biomarkers data were applied using univariate analyses. Multivariate logistic regression analyses were conducted to investigate the association between cerebrovascular disease, vascular profiles, and cognitive impairment. Results: SCD had significantly higher depression scores and poorer quality of life (QOL) compared to CN. MCI had significantly higher depression scores; total MBI symptoms, MBI-interest, MBI-mood, and MBI-beliefs; poorer sleep quality; and poorer QOL compared to CN. Higher Staals scores, glucose levels, and systolic blood pressure were significantly associated with MCI classification. Fasting glucose levels were significantly correlated with depression, anxiety, MBI-social, and poorer sleep quality. Conclusions: The results reflect current research that behavioral changes are among the first symptoms noticeable to the person themselves as they begin to experience cognitive decline. Self-reported questionnaires may aid in early diagnoses of prodromal dementia. Behavioral changes and diabetes could be potential targets for preventative healthcare for dementia.


Subject(s)
Cognitive Dysfunction , Dementia , Humans , Dementia/epidemiology , Quality of Life , Cohort Studies , Southeast Asian People , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/psychology , Biomarkers , Glucose , Neuropsychological Tests
6.
Res Sq ; 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38343795

ABSTRACT

The EMDataResource Ligand Model Challenge aimed to assess the reliability and reproducibility of modeling ligands bound to protein and protein/nucleic-acid complexes in cryogenic electron microscopy (cryo-EM) maps determined at near-atomic (1.9-2.5 Å) resolution. Three published maps were selected as targets: E. coli beta-galactosidase with inhibitor, SARS-CoV-2 RNA-dependent RNA polymerase with covalently bound nucleotide analog, and SARS-CoV-2 ion channel ORF3a with bound lipid. Sixty-one models were submitted from 17 independent research groups, each with supporting workflow details. We found that (1) the quality of submitted ligand models and surrounding atoms varied, as judged by visual inspection and quantification of local map quality, model-to-map fit, geometry, energetics, and contact scores, and (2) a composite rather than a single score was needed to assess macromolecule+ligand model quality. These observations lead us to recommend best practices for assessing cryo-EM structures of liganded macromolecules reported at near-atomic resolution.

7.
Nucleic Acids Res ; 52(8): 4604-4626, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38348908

ABSTRACT

Bacteria have evolved structured RNAs that can associate with RNA polymerase (RNAP). Two of them have been known so far-6S RNA and Ms1 RNA but it is unclear if any other types of RNAs binding to RNAP exist in bacteria. To identify all RNAs interacting with RNAP and the primary σ factors, we have established and performed native RIP-seq in Bacillus subtilis, Corynebacterium glutamicum, Streptomyces coelicolor, Mycobacterium smegmatis and the pathogenic Mycobacterium tuberculosis. Besides known 6S RNAs in B. subtilis and Ms1 in M. smegmatis, we detected MTS2823, a homologue of Ms1, on RNAP in M. tuberculosis. In C. glutamicum, we discovered novel types of structured RNAs that associate with RNAP. Furthermore, we identified other species-specific RNAs including full-length mRNAs, revealing a previously unknown landscape of RNAs interacting with the bacterial transcription machinery.


Subject(s)
Bacillus subtilis , Bacterial Proteins , DNA-Directed RNA Polymerases , Mycobacterium tuberculosis , RNA, Bacterial , Sigma Factor , Sigma Factor/metabolism , Sigma Factor/genetics , DNA-Directed RNA Polymerases/metabolism , DNA-Directed RNA Polymerases/genetics , Bacillus subtilis/genetics , Bacillus subtilis/metabolism , RNA, Bacterial/metabolism , RNA, Bacterial/genetics , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Mycobacterium smegmatis/genetics , Mycobacterium smegmatis/metabolism , Mycobacterium smegmatis/enzymology , Corynebacterium glutamicum/genetics , Corynebacterium glutamicum/metabolism , Streptomyces coelicolor/genetics , Streptomyces coelicolor/metabolism , Gene Expression Regulation, Bacterial , Nucleic Acid Conformation , Transcription, Genetic , RNA, Untranslated
8.
Alzheimers Res Ther ; 16(1): 40, 2024 Feb 17.
Article in English | MEDLINE | ID: mdl-38368378

ABSTRACT

BACKGROUND: The use of structural and perfusion brain imaging in combination with behavioural information in the prediction of cognitive syndromes using a data-driven approach remains to be explored. Here, we thus examined the contribution of brain structural and perfusion imaging and behavioural features to the existing classification of cognitive syndromes using a data-driven approach. METHODS: Study participants belonged to the community-based Biomarker and Cognition Cohort Study in Singapore who underwent neuropsychological assessments, structural-functional MRI and blood biomarkers. Participants had a diagnosis of cognitively normal (CN), subjective cognitive impairment (SCI), mild cognitive impairment (MCI) and dementia. Cross-sectional structural and cerebral perfusion imaging, behavioural scale data including mild behaviour impairment checklist, Pittsburgh Sleep Quality Index and Depression, Anxiety and Stress scale data were obtained. RESULTS: Three hundred seventy-three participants (mean age 60.7 years; 56% female sex) with complete data were included. Principal component analyses demonstrated that no single modality was informative for the classification of cognitive syndromes. However, multivariate glmnet analyses revealed a specific combination of frontal perfusion and temporo-frontal grey matter volume were key protective factors while the severity of mild behaviour impairment interest sub-domain and poor sleep quality were key at-risk factors contributing to the classification of CN, SCI, MCI and dementia (p < 0.0001). Moreover, the glmnet model showed best classification accuracy in differentiating between CN and MCI cognitive syndromes (AUC = 0.704; sensitivity = 0.698; specificity = 0.637). CONCLUSIONS: Brain structure, perfusion and behavioural features are important in the classification of cognitive syndromes and should be incorporated by clinicians and researchers. These findings illustrate the value of using multimodal data when examining syndrome severity and provide new insights into how cerebral perfusion and behavioural impairment influence classification of cognitive syndromes.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Dementia , Humans , Female , Middle Aged , Male , Gray Matter/diagnostic imaging , Cohort Studies , Cross-Sectional Studies , Cognitive Dysfunction/diagnosis , Brain/diagnostic imaging , Cognition , Magnetic Resonance Imaging/methods , Biomarkers , Perfusion/adverse effects , Dementia/complications , Phenotype , Alzheimer Disease/diagnosis
10.
Nat Commun ; 15(1): 1142, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38326301

ABSTRACT

The lasting threat of viral pandemics necessitates the development of tailorable first-response antivirals with specific but adaptive architectures for treatment of novel viral infections. Here, such an antiviral platform has been developed based on a mixture of hetero-peptides self-assembled into functionalized ß-sheets capable of specific multivalent binding to viral protein complexes. One domain of each hetero-peptide is designed to specifically bind to certain viral proteins, while another domain self-assembles into fibrils with epitope binding characteristics determined by the types of peptides and their molar fractions. The self-assembled fibrils maintain enhanced binding to viral protein complexes and retain high resilience to viral mutations. This method is experimentally and computationally tested using short peptides that specifically bind to Spike proteins of SARS-CoV-2. This platform is efficacious, inexpensive, and stable with excellent tolerability.


Subject(s)
COVID-19 , Humans , Peptides/chemistry , SARS-CoV-2/metabolism , Antiviral Agents/pharmacology , Viral Proteins , Spike Glycoprotein, Coronavirus/metabolism
11.
Nat Commun ; 15(1): 567, 2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38238298

ABSTRACT

Due to the paucity of longitudinal molecular studies of COVID-19, particularly those covering the early stages of infection (Days 1-8 symptom onset), our understanding of host response over the disease course is limited. We perform longitudinal single cell RNA-seq on 286 blood samples from 108 age- and sex-matched COVID-19 patients, including 73 with early samples. We examine discrete cell subtypes and continuous cell states longitudinally, and we identify upregulation of type I IFN-stimulated genes (ISGs) as the predominant early signature of subsequent worsening of symptoms, which we validate in an independent cohort and corroborate by plasma markers. However, ISG expression is dynamic in progressors, spiking early and then rapidly receding to the level of severity-matched non-progressors. In contrast, cross-sectional analysis shows that ISG expression is deficient and IFN suppressors such as SOCS3 are upregulated in severe and critical COVID-19. We validate the latter in four independent cohorts, and SOCS3 inhibition reduces SARS-CoV-2 replication in vitro. In summary, we identify complexity in type I IFN response to COVID-19, as well as a potential avenue for host-directed therapy.


Subject(s)
COVID-19 , Interferon Type I , Humans , Cross-Sectional Studies , SARS-CoV-2 , Up-Regulation
12.
J Biomol Struct Dyn ; 42(5): 2392-2409, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37160699

ABSTRACT

Cancer is an unimpeded growth of cells leading to metathesis of cancer and eventually spread throughout the body. PIM kinases are the members of the serine threonine kinase playing role in cancer progression, differentiation and proliferation. Till date there is no single drug targeting PIM-1 kinase in the market, that has made itself a target in limelight for the discover of new anticancer agents. The contemporary research focusses on the development of new inhibitors of PIM-1 kinase by application of ligand-based and structure-based perspective of drug discovery namely 3D-QSAR, molecular docking and dynamics. The following study stated the correlation amid structural and biological activity of the compounds employing 3D-QSAR analysis. Three 3D-QSAR models were generated using 33 molecules from which the excellent model stated an encouraging conventional correlation coefficient (r2) 0.8651, cross validation coefficient (q2) 0.7609. Furthermore, the predicted correlation coefficient (r2 pred) 0.6274, respectively. Molecular docking studies revealed that the most active compound 26 resided in the active pocket of PIM-1 kinase establishing hydrogen bond interactions with Asp186 in the DFG motif; similarly, all other molecules were engaged within the active site of the PIM-1 kinase. Moreover, molecular dynamics simulation study stated the stability of the ligand in the active site of PIM-1 kinase protein by developing two hydrogen bonds throughout the trajectory of 100 ns. In nutshell, the output stated the successful application of ligand and structure-based strategy for the development of novel PIM-1 kinase inhibitors as anticancer agents.Communicated by Ramaswamy H. Sarma.


Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Molecular Dynamics Simulation , Molecular Docking Simulation , Proto-Oncogene Proteins c-pim-1 , Quantitative Structure-Activity Relationship , Ligands , Antineoplastic Agents/pharmacology
13.
Water Sci Technol ; 88(11): 2873-2888, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38096075

ABSTRACT

The water quality of Himalayan rivers has declined due to human activities, untreated effluent discharge, and poor sewage and drainage systems. The current study aimed to assess the water quality of these rivers using multivariate statistical analysis throughout four seasons. The analyses of 44 surface water samples taken during the monsoon, winter, spring, and summer seasons are well within the ranges acceptable for drinking and domestic use after the sedimentation. The suspended soils and turbidity are highly correlated and affect the water quality index (WQI). The WQI of headwater streams is good during low water flow seasons and poor during high water flow seasons. This is due to the number of melting glaciers and suspended solids/turbidity. Principal component analysis shows that in all the seasons, human activities such as road-cutting projects across the river and natural causes such as intense rainfall and melting of moraine-filled glaciers both impact the WQI. The findings of this study provide important information for future research and policy decisions aimed at improving the water quality of the Himalayan rivers.


Subject(s)
Environmental Monitoring , Rivers , Water Quality , Ice Cover , Seasons , Snow , Himalayas
14.
Front Plant Sci ; 14: 1275854, 2023.
Article in English | MEDLINE | ID: mdl-38023864

ABSTRACT

Peanut Arachis hypogaea is a segmental allotetraploid in the section Arachis of the genus Arachis along with the Section Rhizomataceae. Section Arachis has several diploid species along with Arachis hypogaea and A. monticola. The section Rhizomataceae comprises polyploid species. Several species in the genus are highly tolerant to biotic and abiotic stresses and provide excellent sets of genotypes for studies on differential gene expression. Though there were several studies in this direction, more studies are needed to identify more and more gene combinations. Next generation RNA-seq based differential gene expression study is a powerful tool to identify the genes and regulatory pathways involved in stress tolerance. Transcriptomic and proteomic study of peanut plants under biotic stresses reveals a number of differentially expressed genes such as R genes (NBS-LRR, LRR-RLK, protein kinases, MAP kinases), pathogenesis related proteins (PR1, PR2, PR5, PR10) and defense related genes (defensin, F-box, glutathione S-transferase) that are the most consistently expressed genes throughout the studies reported so far. In most of the studies on biotic stress induction, the differentially expressed genes involved in the process with enriched pathways showed plant-pathogen interactions, phenylpropanoid biosynthesis, defense and signal transduction. Differential gene expression studies in response to abiotic stresses, reported the most commonly expressed genes are transcription factors (MYB, WRKY, NAC, bZIP, bHLH, AP2/ERF), LEA proteins, chitinase, aquaporins, F-box, cytochrome p450 and ROS scavenging enzymes. These differentially expressed genes are in enriched pathways of transcription regulation, starch and sucrose metabolism, signal transduction and biosynthesis of unsaturated fatty acids. These identified differentially expressed genes provide a better understanding of the resistance/tolerance mechanism, and the genes for manipulating biotic and abiotic stress tolerance in peanut and other crop plants. There are a number of differentially expressed genes during biotic and abiotic stresses were successfully characterized in peanut or model plants (tobacco or Arabidopsis) by genetic manipulation to develop stress tolerance plants, which have been detailed out in this review and more concerted studies are needed to identify more and more gene/gene combinations.

15.
Article in English | MEDLINE | ID: mdl-37968064

ABSTRACT

An outbreak of food poisoning of unknown origin was notified to Central Queensland Public Health Unit on 9 December 2021. The bulk carrier sailing from Higashiharima, Japan to Gladstone, Australia reported an incident of sudden illness, with 19 out of 20 sailors on board reporting a combination of gastrointestinal and neurological symptoms. Central Queensland Public Health Unit started the outbreak investigation as per Queensland Health public health management guidelines. All 20 of the sailors consumed a self-caught barracuda and squid, prepared by the ship's cook, the day before. Unconsumed samples of the fish and squid were sent for testing. The affected sailors were triaged on arrival and were provided with medical care as required. The barracuda sample contained ciguatoxins (CTXs; P-CTX-1, P-CTX-2, P-CTX-3) with a total count of 3.40 ug/kg confirming the diagnosis. We propose the usage of the combination of gastrointestinal symptoms and paraesthesia in the light of a recent intoxication event for early detection of ciguatera poisoning (CP) in the eastern seaboard of Australia.


Subject(s)
Ciguatera Poisoning , Ciguatoxins , Animals , Humans , Ciguatera Poisoning/diagnosis , Ciguatera Poisoning/epidemiology , Australia/epidemiology , Disease Outbreaks/prevention & control , Early Diagnosis
16.
Cureus ; 15(9): e45260, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37846260

ABSTRACT

Background Atrial septal defect (ASD) closure with significant left-to-right shunt and concurrent comorbidities poses challenges for intervention. A fenestrated atrial septal defect (FASD) device is a viable option for patients who cannot undergo complete occlusion due to hemodynamic and medical reasons. This study explores the use of FASD occluders in patients with secundum ASD and associated comorbidities where complete occlusion is difficult. Methodology This retrospective study collected the details of patients recommended for FASD closure diagnosed with significant secundum ASD and who had additional comorbidities between July 2015 and July 2023 in a tertiary cardiac center in eastern India. Among this cohort, patients who underwent FASD device placement were subjected to a comprehensive analysis. Results In total, 16 patients diagnosed with secundum ASD, characterized by significant left-to-right shunt and concurrent comorbidities, were considered for FASD closure during the study period. Ultimately, 13 patients (first group) underwent fenestrated atrial septal occluder implantation. The average age was 45.07 years, with the majority being females (n = 9). Comorbidities among this cohort included substantial left ventricular diastolic dysfunction (n = 7), left ventricular diastolic dysfunction coupled with moderate pulmonary hypertension (n = 1), severe pulmonary hypertension (n = 1), severe pulmonary valvular stenosis with right ventricular diastolic dysfunction (n = 2), and systemic lupus erythematosus (SLE) (n = 2). From this cohort, three patients did not undergo the intervention. The second group consisted of an elderly patient with severe left ventricular diastolic dysfunction, a young adult with a history of left atrial arrhythmia, and a child with Duchenne muscular dystrophy (DMD). The average ASD size among patients who underwent the intervention was 26.38 mm, with a thick-to-thick dimension measuring 31.15 mm. The procedure was successful in all 13 patients, with the most frequently used device being a 34 mm occluder (range = 28-40 mm). All devices, excluding the initial one, were custom-made atrial septal occluders (Lifetech Scientific). Among the patients, 12 exhibited left-to-right fenestration flow, while one patient experienced fenestration constriction, likely due to occluder overcrowding. The first patient had a handmade 5 mm fenestration in a 40 mm Amplatzer septal occluder, which got closed off at the one-year follow-up. The procedure was well-tolerated hemodynamically in all patients, with no major complications during the peri-procedural period. Short-term follow-up indicated favorable patient progress. Conclusions FASD closure emerges as a pivotal alternative for intricate scenarios involving secundum ASD coupled with concurrent comorbidities, offering individualized tailored solutions. Alongside the conventional associated comorbidities, such as left ventricular diastolic dysfunction and pulmonary hypertension, FASD devices hold the potential to extend their benefits to patients grappling with other complexities, including severe pulmonary valvular stenosis, SLE, predisposition to left atrial arrhythmia, and conditions like DMD. Ensuring meticulous evaluation of patient suitability and providing ongoing vigilant care becomes paramount for achieving optimal outcomes. The validation of these findings and the broadening of the comprehension of this approach necessitate further comprehensive investigations.

17.
Cell Chem Biol ; 30(10): 1211-1222.e5, 2023 10 19.
Article in English | MEDLINE | ID: mdl-37827156

ABSTRACT

The small-molecule drug ralimetinib was developed as an inhibitor of the p38α mitogen-activated protein kinase, and it has advanced to phase 2 clinical trials in oncology. Here, we demonstrate that ralimetinib resembles EGFR-targeting drugs in pharmacogenomic profiling experiments and that ralimetinib inhibits EGFR kinase activity in vitro and in cellulo. While ralimetinib sensitivity is unaffected by deletion of the genes encoding p38α and p38ß, its effects are blocked by expression of the EGFR-T790M gatekeeper mutation. Finally, we solved the cocrystal structure of ralimetinib bound to EGFR, providing further evidence that this drug functions as an ATP-competitive EGFR inhibitor. We conclude that, though ralimetinib is >30-fold less potent against EGFR compared to p38α, its ability to inhibit EGFR drives its primary anticancer effects. Our results call into question the value of p38α as an anticancer target, and we describe a multi-modal approach that can be used to uncover a drug's mechanism-of-action.


Subject(s)
Lung Neoplasms , Mitogen-Activated Protein Kinase 14 , Humans , ErbB Receptors , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Mutation , Mitogen-Activated Protein Kinase 14/genetics , Mitogen-Activated Protein Kinase 14/metabolism
18.
Cureus ; 15(8): e43105, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37692751

ABSTRACT

BACKGROUND: Overweight and obesity among school-going children is an emerging public health problem in the country. The information available on the true extent of obesity and overweight among school-aged children is limited. Hence, the present study has been conducted to determine the prevalence of overweight and obesity among high school students in Jharkhand, India. METHODOLOGY: This was a cross-sectional study conducted among 1162 students of government and private schools of Ormanjhi block, Ranchi district, from July 2022 to December 2022. A predesigned, semi-structured, pre-tested questionnaire containing different sections namely sociodemographic characteristics, and health parameters were used for the study subjects. Clinical examination and anthropometric measurements of height, weight, and waist and hip circumferences were taken using standard equipment to calculate body mass index (BMI) and central obesity (waist-hip ratio). RESULTS: The prevalence of overweight and obesity was more at 14 years of age (30.2%), among boys (18.1%), and among students practicing the Islam religion (51.1%). Moreover, the prevalence of overweight and obesity was found to be highest in private schools (66.2%), and that was statistically significant (p<0.001). CONCLUSION: The prevalence of overweight and obesity was found to be significant with respect to age, gender, and religion. The findings from this study would be helpful in raising awareness among students, parents, teachers, and health professionals about the influence of overweight and obesity on a child's physical, social, and psychological well-being, and this, in turn, would facilitate parents, students, and teachers in the adoption of a healthy lifestyle.

19.
F1000Res ; 12: 516, 2023.
Article in English | MEDLINE | ID: mdl-37274828

ABSTRACT

Background: Bibliometric analysis is an approach adopted by researchers to understand the various analytics such as year-wise publications, their citations, most impactful authors and their contributions, identification of emerging keywords, multiple themes (niche, motor, basic, and emerging or declining) etc. F1000Research is one of the Q1 category journals that publishes articles in various domains, but a detailed journal analysis is yet to be done. Methods: This study is an effort to extract the F1000Research journey information through bibliometric analysis using VOS-viewer and Biblioshiny (R-studio) interface. The F1000Research journal started its journey in 2012; since then, 5767 articles have been published until the end of 2022. Most of the published articles are from medical science, covering Biochemistry, Genetics & Molecular Biology, Immunology & Pharmacology, Toxicology & Pharmaceutics. To understand the research journey, various analyses such as publication & citation trends, leading authors, institutions, countries, most frequent keywords, bibliographic coupling between authors, countries and documents, emerging research themes, and trending keywords were performed. Results: The United States is the biggest contributor, and COVID-19 is the most commonly occurred keyword. Conclusions: The present study may help future researchers to understand the emerging medical science domain. It will also help the editors and journal to focus more on developing or emerging areas and to understand their importance towards society. Future researchers can contribute their quality research studies, focusing on emerging themes. These authors' research can guide future researchers to develop their research area around the most impacted articles. They can collaborate with them to bring that emerging theme forward.


Subject(s)
COVID-19 , United States , Humans , Bibliometrics , Publications
20.
Front Nutr ; 10: 1110750, 2023.
Article in English | MEDLINE | ID: mdl-37275642

ABSTRACT

Underutilized/orphan legumes provide food and nutritional security to resource-poor rural populations during periods of drought and extreme hunger, thus, saving millions of lives. The Leguminaceae, which is the third largest flowering plant family, has approximately 650 genera and 20,000 species and are distributed globally. There are various protein-rich accessible and edible legumes, such as soybean, cowpea, and others; nevertheless, their consumption rate is far higher than production, owing to ever-increasing demand. The growing global urge to switch from an animal-based protein diet to a vegetarian-based protein diet has also accelerated their demand. In this context, underutilized legumes offer significant potential for food security, nutritional requirements, and agricultural development. Many of the known legumes like Mucuna spp., Canavalia spp., Sesbania spp., Phaseolus spp., and others are reported to contain comparable amounts of protein, essential amino acids, polyunsaturated fatty acids (PUFAs), dietary fiber, essential minerals and vitamins along with other bioactive compounds. Keeping this in mind, the current review focuses on the potential of discovering underutilized legumes as a source of food, feed and pharmaceutically valuable chemicals, in order to provide baseline data for addressing malnutrition-related problems and sustaining pulse needs across the globe. There is a scarcity of information about underutilized legumes and is restricted to specific geographical zones with local or traditional significance. Around 700 genera and 20,000 species remain for domestication, improvement, and mainstreaming. Significant efforts in research, breeding, and development are required to transform existing local landraces of carefully selected, promising crops into types with broad adaptability and economic viability. Different breeding efforts and the use of biotechnological methods such as micro-propagation, molecular markers research and genetic transformation for the development of underutilized crops are offered to popularize lesser-known legume crops and help farmers diversify their agricultural systems and boost their profitability.

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