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1.
J Org Chem ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701377

RESUMO

An earth-abundant Co(II) salt-catalyzed mild and affordable synthetic route has been developed for the synthesis of industrially relevant 1,4-dicarbonyl compounds (or γ-diketones) via oxidative coupling between aryl alkenes and ketones (both cyclic and acyclic) using TBHP and DBU as the oxidant and base, respectively. 1,4-Dicarbonyl compounds are known to be synthesized using expensive metal catalysts, dual catalysts, or low-cost metal complexes combined with an additive or ligand template, which further needs to be synthesized. Herein, we report the synthesis of 1,4-dicarbonyl compounds using cobalt(II) acetate as a catalyst without any expensive co-catalyst or ligand templates. This methodology has a broad substrate scope with significant yields and good functional group tolerance. Generation of unsymmetrical 1,4-dicarbonyls at room temperature and its versatile synthetic expansion to produce synthetically and biologically valuable heterocyclic compounds are salient features of this novel methodology. In addition, various controlled experiments such as primary kinetic isotope effect study, Hammett analysis with variation of the nature of the substituents on the styrene ring, and theoretical calculations (density functional theory) unravel the mechanistic intricacies involved in this new, simple, and atom-economic methodology.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38649601

RESUMO

Phosphorus to an optimum extent is an essential nutrient for all living organisms and its scarcity may cause food security, and environmental preservation issues vis-à-vis agroeconomic hurdles. Undesirably excess phosphorus intensifies the eutrophication problem in non-marine water bodies and disrupts the natural nutrient balance of the ecosystem. To overcome such dichotomy, biodegradable polymer-based adsorbents have emerged as a cost-effective and implementable approach in striking a "desired optimum-undesired excess" balance pertaining to phosphate in a sustainable manner. So far, the reports on adopting such adsorbent-approach for wastewater remediation remained largely scattered, unstructured, and poorly correlated. In this background, the contextual review comprehensively discusses the current state-of-the-art in utilizing biodegradable polymeric frameworks as an adsorbent system for phosphate removal and its efficient recovery from the aquatic ecosystem, while highlighting their characteristics-specific functional efficiency vis-à-vis easiness of synthetic and commercial viability. The overview further delves into the sources and environmental ramifications of excessive phosphorus in water bodies and associated mechanistic pathways of phosphorus removal via adsorption, precipitation, and membrane filtration enabled by biodegradable (natural and synthetic) polymeric substrates. Finally, functionality optimization, degradability tuning, and adsorption selectivity of biodegradable polymers are highlighted, while aiming to strike a balance in "removal-recovery-reuse" dynamics of phosphate. Thus, the current review not only paves the way for future exploration of biodegradable polymers in sustainable cost-effective adsorbents for phosphorus removal but also can serve as a guide for researchers dealing with this critical issue.

3.
Brain ; 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643018

RESUMO

Neuropsychological impairments are common in children with drug-resistant epilepsy. It has been proposed that epilepsy surgery may alleviate these impairments by providing seizure freedom; however, findings from prior studies have been inconsistent. We mapped long-term neuropsychological trajectories in children before and after undergoing epilepsy surgery, to measure the impact of disease course and surgery on functioning. We performed a retrospective cohort study of 882 children who had undergone epilepsy surgery at Great Ormond Street Hospital (1990-2018). We extracted patient information and neuropsychological functioning - obtained from IQ tests (domains: Full-Scale IQ, Verbal IQ, Performance IQ, Working Memory, and Processing Speed) and tests of academic attainment (Reading, Spelling and Numeracy) - and investigated changes in functioning using regression analyses. We identified 500 children (248 females) who had undergone epilepsy surgery (median age at surgery = 11.9 years, interquartile range = [7.8,15.0]) and neuropsychology assessment. These children showed declines in all domains of neuropsychological functioning in the time leading up to surgery (all p-values ≤ 0.001; e.g., ßFSIQ = -1.9, SEFSIQ = 0.3, pFSIQ < 0.001). Children lost on average one to four points per year, depending on the domain considered; 27-43% declined by 10 or more points from their first to their last preoperative assessment. At the time of presurgical evaluation, most children (46-60%) scored one or more standard deviations below the mean (<85) on the different neuropsychological domains; 37% of these met the threshold for intellectual disability (Full-Scale IQ < 70). On a group level, there was no change in performance from pre- to postoperative assessment on any of the domains (all p-values > 0.128). However, children who became seizure-free through surgery showed higher postoperative neuropsychological performance (e.g., rrb-FSIQ = 0.37, p < 0.001). These children continued to demonstrate improvements in neuropsychological functioning over the course of their long-term follow-up (e.g., ßFSIQ = 0.9, SEFSIQ = 0.3, pFSIQ = 0.004). Children who had discontinued antiseizure medication (ASM) treatment at one-year follow-up showed an eight-to-13-point advantage in postoperative Working Memory, Processing Speed, and Numeracy, and greater improvements in Verbal IQ, Working Memory, Reading, and Spelling (all p-values < 0.034) over the postoperative period compared to children who were seizure-free and still receiving ASMs. In conclusion, by providing seizure freedom and the opportunity for ASM cessation, epilepsy surgery may not only halt but reverse the downward trajectory that children with drug-resistant epilepsy display in neuropsychological functioning. To halt this decline as soon as possible, or potentially prevent it from occurring in the first place, children with focal epilepsy should be considered for epilepsy surgery as early as possible after diagnosis.

4.
Medicine (Baltimore) ; 103(1): e36876, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38181236

RESUMO

Decompressive craniectomy (DC) is a well-established neurosurgical intervention in patients with high intracranial pressure who fail to respond to medical treatment. Data on predictive factors for functional outcomes in patients with DC who have malignant middle cerebral artery (MCA) infarction as opposed to intracranial hemorrhage (ICH) are scarce. Eighty-four patients who underwent DC treatment for ICH and malignant MCA infarction were examined. All patients underwent surgery in the Bahrain Salmaniya Medical Complex Neurosurgery Unit between January 2017 and June 2021. To determine whether any of these demonstrated a link to the functional outcome, radiographic factors were compared with clinical data. The postsurgical midline shift (MLS) (ICH group) showed the strongest correlation (ρ = 0.434; P = .006), as in the MCA infarction group as well (ρ = 0.46; P = .005). Further analyses using binary logistic regression with postsurgical basal cistern status and ∆ MLS, and it was observed to be statistically significant (odds ratios: 0.067, 95% CI: 0.007, 0.67; P = .021). The initial Glasgow coma scale, postsurgical MLS, basal cistern status, and ∆ are Measurable variables that can be used to predict outcomes in the groups with ICH and MCA infarction.


Assuntos
Craniectomia Descompressiva , Humanos , Prognóstico , Estudos Retrospectivos , Infarto da Artéria Cerebral Média/cirurgia , Academias e Institutos , Hemorragias Intracranianas
5.
Org Biomol Chem ; 22(5): 1034-1037, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38197231

RESUMO

A metal-free, visible-light-mediated C-H silylation of 2H-indazoles with triphenylsilane has been developed employing 4CzIPN as a photocatalyst and triisopropylsilanethiol as a hydrogen atom transfer (HAT) reagent under aerobic reaction conditions. This method shows tolerance toward many functional groups and affords a variety of silylated indazoles at up to 89% yield. The experimental results suggest that the reaction progresses through a radical pathway.

6.
Dev Med Child Neurol ; 66(2): 216-225, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37559345

RESUMO

AIM: To evaluate a lesion detection algorithm designed to detect focal cortical dysplasia (FCD) in children undergoing stereoelectroencephalography (SEEG) as part of their presurgical evaluation for drug-resistant epilepsy. METHOD: This was a prospective, single-arm, interventional study (Idea, Development, Exploration, Assessment, and Long-Term Follow-Up phase 1/2a). After routine SEEG planning, structural magnetic resonance imaging sequences were run through an FCD lesion detection algorithm to identify putative clusters. If the top three clusters were not already sampled, up to three additional SEEG electrodes were added. The primary outcome measure was the proportion of patients who had additional electrode contacts in the SEEG-defined seizure-onset zone (SOZ). RESULTS: Twenty patients (median age 12 years, range 4-18 years) were enrolled, one of whom did not undergo SEEG. Additional electrode contacts were part of the SOZ in 1 out of 19 patients while 3 out of 19 patients had clusters that were part of the SOZ but they were already implanted. A total of 16 additional electrodes were implanted in nine patients and there were no adverse events from the additional electrodes. INTERPRETATION: We demonstrate early-stage prospective clinical validation of a machine learning lesion detection algorithm used to aid the identification of the SOZ in children undergoing SEEG. We share key lessons learnt from this evaluation and emphasize the importance of robust prospective evaluation before routine clinical adoption of such algorithms. WHAT THIS PAPER ADDS: The focal cortical dysplasia detection algorithm collocated with the seizure-onset zone (SOZ) in 4 out of 19 patients. The algorithm changed the resection boundaries in 1 of 19 patients undergoing stereoelectroencephalography for drug-resistant epilepsy. The patient with an altered resection due to the algorithm was seizure-free 1 year after resective surgery. Overall, the algorithm did not increase the proportion of patients in whom SOZ was identified.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Displasia Cortical Focal , Criança , Humanos , Pré-Escolar , Adolescente , Eletroencefalografia/métodos , Estudos Retrospectivos , Epilepsia/diagnóstico , Epilepsia/cirurgia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Convulsões
7.
Chemistry ; 30(8): e202303776, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38055713

RESUMO

We report the Cu(II) catalyzed synthesis of ß-disubstituted ketones from styrene via oxo-alkylation with unactivated cycloalkanes as the alkylating agent in presence of tert-butylhydroperoxide (TBHP) and 1-methylimidazole as oxidant and base respectively. ß-disubstituted ketones are known to be synthesized by using either expensive Ru/Ir complexes, or low-cost metal complexes (e. g., Fe, Mn) with activated species like aldehyde, acid, alcohol, or phthalimide derivatives as the alkylating agent, however, use of unactivated cycloalkanes directly as the alkylating agent remains challenging. A wide range of aliphatic C-H substrates as well as various olefinic arenes and heteroarene (35 substrates including 14 new substrates) are well-tolerated in this method. Hammett analysis shed more light on the substitution effect in the olefinic part on the overall mechanism. Furthermore, the controlled experiments, kinetic isotope effect study, and theoretical calculations (DFT) enable us to gain deeper insight of mechanistic intricacies of this new simple and atom-economic methodology.

8.
Chemistry ; 30(4): e202302849, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-37870380

RESUMO

The oxidant-controlled divergent synthesis of C-2' formyl 2H-indazoles and indazoloindazolediones has been developed through Mn(I)- catalyzed ortho C-H functionalization of 2H-indazoles with para-formaldehyde to afford C-2' hydroxymethylated 2H-indazoles and subsequently oxidation with varying the amount of DDQ in one-pot. By employing selectfluor as the oxidant instead of DDQ, this reaction exclusively provided indazolebenzoxazine derivatives. This strategy delivered unsymmetrical indazoloindazoledione and indazolobenzoxazine with varied functional group tolerance in moderate to good yields.

9.
Plant Commun ; 4(6): 100726, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37789617

RESUMO

Rapid climate change has led to enhanced soil salinity, one of the major determinants of land degradation, resulting in low agricultural productivity. This has a strong negative impact on food security and environmental sustainability. Plants display various physiological, developmental, and cellular responses to deal with salt stress. Recent studies have highlighted the root cap as the primary stress sensor and revealed its crucial role in halotropism. The root cap covers the primary root meristem and is the first cell type to sense and respond to soil salinity, relaying the signal to neighboring cell types. However, it remains unclear how root-cap cells perceive salt stress and contribute to the salt-stress response. Here, we performed a root-cap cell-specific proteomics study to identify changes in the proteome caused by salt stress. The study revealed a very specific salt-stress response pattern in root-cap cells compared with non-root-cap cells and identified several novel proteins unique to the root cap. Root-cap-specific protein-protein interaction (PPI) networks derived by superimposing proteomics data onto known global PPI networks revealed that the endoplasmic reticulum (ER) stress pathway is specifically activated in root-cap cells upon salt stress. Importantly, we identified root-cap-specific jacalin-associated lectins (JALs) expressed in response to salt stress. A JAL10-GFP fusion protein was shown to be localized to the ER. Analysis of jal10 mutants indicated a role for JAL10 in regulating the ER stress pathway in response to salt. Taken together, our findings highlight the participation of specific root-cap proteins in salt-stress response pathways. Furthermore, root-cap-specific JAL proteins and their role in the salt-mediated ER stress pathway open a new avenue for exploring tolerance mechanisms and devising better strategies to increase plant salinity tolerance and enhance agricultural productivity.


Assuntos
Proteínas de Plantas , Proteoma , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteoma/metabolismo , Lectinas , Estresse do Retículo Endoplasmático , Plantas/metabolismo , Solo
10.
Chem Asian J ; 18(22): e202300755, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37814533

RESUMO

Acyl hydrazones are a class of synthetically important organic compounds that are recurrently in high demand for synthesis and use in various fields of chemistry and biology. We report the first Co(II) catalyzed one-component one-pot sustainable synthesis of acyl hydrazones only from acyl hydrazides under mild reaction conditions. Traditional and contemporary methodologies use two components (usually acyl hydrazides and aldehydes/ketones/alcohols/styrene) as the coupling partners. Our protocol, on the other hand, involves the in situ generation of aldehyde intermediate (detected by gas chromatography) from the acyl hydrazide, which then undergoes condensation with another molecule of the same acyl hydrazide in the same pot to yield acyl hydrazones in presence of mild base K2 CO3 and low-cost Co(OAc)2 ⋅ 4H2 O as catalyst. This method shows good functional group tolerance with good to excellent yield of products. Furthermore, some of the resulting acyl hydrazones have been used as synthetic precursors and explored in various post-synthetic modifications to afford N-heterocyclic compounds. Furthermore, photoswitchable properties of few synthesized acyl hydrazones are also explored using their E/Z isomerization around the C=N bond, as realized by high-pressure liquid chromatography (HPLC) and UV-vis spectroscopic studies.

11.
Soft Matter ; 19(42): 8264-8273, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37869972

RESUMO

Self-assembled supramolecular hydrogels offer great potential as biomaterials and drug delivery systems. Specifically, peptide-based multicomponent hydrogels are promising materials due to their advantage that their mechanical and physical properties can be tuned to enhance their functionalities and broaden their applications. Herein, we report two-component assembly and formation of hydrogels containing inexpensive complementary anionic, BUVV-OH (A), and cationic, KFFC12 (B), peptide amphiphiles. Individually, neither of these components formed a hydrogel, while mixtures with compositions 1 : 1, 1 : 2, and 2 : 1 (molar ratio) as A : B show hydrogel formation (Milli-Q water, at pH = 6.79). These hydrogels displayed a good shear-thinning behaviour with different mechanical stabilities and nano-fibrous network structures. The 1 : 1 hydrogel shows good cell viability for human embryonic kidney (HEK-293) cells and CHO cells indicating its non-cytotoxicity. The biocompatible, thixotropic 1 : 1 hydrogel with a nanofiber network structure shows the highest mechanical strength with a storage modulus of 3.4 × 103 Pa. The hydrogel is able to encapsulate drugs including antibiotics amoxicillin and rifampicin, and anticancer drug doxorubicin, and it exhibits sustainable release of 76%, 70%, and 81% respectively in vitro after 3 days. The other two mixtures (composition 1 : 2 and 2 : 1) are unable to form a hydrogel when they are loaded with these drugs. Interestingly, it is noticed that with an increase in concentration, the mechanical strength of a 1 : 1 hydrogel is significantly enhanced, showing potential that may act as a scaffold for tissue engineering. The two-component gel offers tunable mechanical properties, thixotropy, injectability, and biocompatibility and has great potential as a scaffold for sustained drug release and tissue engineering.


Assuntos
Hidrogéis , Peptídeos , Animais , Cricetinae , Humanos , Hidrogéis/química , Liberação Controlada de Fármacos , Cricetulus , Células HEK293
12.
Aquat Toxicol ; 263: 106673, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37669601

RESUMO

Methylmercury (MeHg) is a pervasive environmental contaminant in aquatic ecosystems that can reach elevated concentrations in fish of high trophic levels, such as salmonids. The present study aims at investigating the individual and combined impacts of dietary MeHg and fatty acids on lipid metabolism in juvenile rainbow trout (Oncorhynchus mykiss) with a focus on two key organs, adipose tissue and liver. MeHg and fatty acids are both known to act on energy homeostasis although little is known about their interplay on lipid metabolism in fish. Fish were fed diets enriched in linoleic acid (LA, 18:2 n-6), α-linolenic acid (ALA, 18:3 n-3), eicosapentaenoic acid (EPA, 20:5 n-3) or docosahexaenoic acid (DHA, 22:6 n-3) for ten weeks, with the addition of MeHg to the diets during the last six weeks (0, 2.4 or 5.5 mg MeHg/kg dry matter). LA and ALA are polyunsaturated fatty acids (PUFA) typical of plant-derived oils whereas EPA and DHA are n-3 long chain PUFA largely found in fish oil, all used in feed formulation in aquaculture. The results showed that the LA-enriched diet induced a higher whole-body lipid content compared to the three other diets. On the contrary, the addition of MeHg led to a significant reduction of the whole-body lipid content, regardless of the diet. Interestingly, the adipocytes were larger both in presence of LA, compared to EPA and DHA, or MeHg, indicating a lipogenic effect of these two compounds. No effect was, however, observed on lipid accumulation per gram of adipose tissue. The fatty acid composition of adipose tissue and liver was significantly modified by the dietary lipids, reflecting both the fatty acid composition of the diets and the high bioconversion capacity of the rainbow trout. Exposure to MeHg selectively led to a release of n-6 PUFA from the hepatic membranes of fish fed the LA-enriched diet, showing a disruption of the pathways using n-6 PUFA. This study highlights the significant impact of MeHg exposure and dietary fatty acids on lipid metabolism in fish. Further investigation is needed to elucidate the underlying mechanisms and to explore the potential involvement of other organs.


Assuntos
Compostos de Metilmercúrio , Oncorhynchus mykiss , Poluentes Químicos da Água , Animais , Ácidos Graxos/metabolismo , Oncorhynchus mykiss/metabolismo , Compostos de Metilmercúrio/toxicidade , Compostos de Metilmercúrio/metabolismo , Metabolismo dos Lipídeos , Ecossistema , Poluentes Químicos da Água/toxicidade , Fígado , Dieta/veterinária , Ácidos Docosa-Hexaenoicos/farmacologia , Tecido Adiposo
13.
Environ Res ; 237(Pt 1): 116889, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37595826

RESUMO

Information on pollutant trophodynamics can be crucial for public health, as contaminated food consumption may lead to deleterious effects. This study was performed in Puruzinho Lake, a remote body of water in the Brazilian Amazon from which a riparian human population obtains an important part of its animal protein intake. Samples from 92 individuals, comprising 13 species and four trophic guilds (iliophagous, planktivorous, omnivorous, and piscivorous fish) were analysed for the determination of trace elements (Fe, Cr, Mn, Ni, Zn, Ca, Sr, Cd, Sn, Tl and Pb) and methylmercury concentrations. Samples from the same individuals had already been analysed for stable isotope (SI) measurements (δ13C and δ15N) in a previous investigation and the SI data have been statistically treated with those generated in this study for the evaluation of trophic dynamics of contaminants. Methylmercury was the only analyte that biomagnified, presenting TMF values of 4.65 and 4.55 for total and resident ichthyofauna, respectively. Trace elements presented either trophic dilution or independence from the trophic position, constituting a behaviour that was coherent with that found in the scientific literature. The similarity between Ni behaviour through the trophic web to that of essential elements contributes to the discussion on the essentiality of this metal to fish. Considering the Non-cancer Risk Assessment, the calculated Target Hazard Quotient (THQ) values were higher than 1.0 for all analysed individuals for methylmercury, as well as for only one individual for nickel. No other analyte rendered THQ values higher than 1.0.

14.
Cureus ; 15(5): e39674, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37398705

RESUMO

Endovascular procedures have become a mainstay in the treatment of neurovascular pathologies like arteriovenous malformations and aneurysms. Catheter-induced blister-like aneurysms (BBAs) have not been described so far in the neurosurgical literature. The authors report a rare case of a possible, catheter-induced (iatrogenic) BBA of the supra-ventral wall of the internal carotid artery (ICA) post-endovascular coiling for posterior communicating artery (PComA) aneurysm and bring the rapid progression of BBA and the grade prognosis. A 46-year-old female presented with convulsions. Imaging studies showed diffuse subarachnoid haemorrhage (SAH) and a right saccular PComA aneurysm. Endovascular coiling of the aneurysm was performed, and it was uneventful. The patient had a good outcome (modified Rankin Scale of 1) with no neurological deficits and was discharged home on day five. However, on day nine after the first ictus, she experienced a severe headache at home and was rushed to the emergency room where she collapsed. A cranial computed tomography scan showed intracerebral haemorrhage with intraventricular extension and SAH. A cerebral angiogram showed a BBA of the supra-ventral wall of the ICA. A BBA needs to be considered as a complication of an endovascular procedure that may result in rapid neurological deterioration post-coiling due to rupture. The report also illustrates the rapid and catastrophic presentation of BBA.

15.
Eur Arch Otorhinolaryngol ; 280(9): 4295-4298, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37329357

RESUMO

BACKGROUND: Post-styloid parapharyngeal space tumours (PPS) have a notorious course owing to their anatomy and proximity to neurovascular bundles. Nerve injuries are usual outcomes in schwannomas. Our case is the first documented complication of contralateral hemiplegia occurring in the postoperative period in a benign PPS tumour. CASE REPORT: A 24-year-old presented with a swelling on the left lateral aspect of the neck, diagnosed as a PPS schwannoma. He underwent transcervical excision with mandibulotomy with extracapsular dissection of the tumour. Contralateral hemiplegia, as a dreaded complication, was encountered. He was managed conservatively according to ASPECTS stroke guidelines by the critical care team. On a regular follow-up, he noticed an improvement in the lower limb with subsequent upper limb power. CONCLUSION: Perioperative stroke is a dreaded complication involving PPS in large benign tumours. To prevent unforeseen circumstances, necessary preoperative patient counselling and immense intraoperative care should be taken while dissecting the major vessels.


Assuntos
Neurilemoma , Acidente Vascular Cerebral , Masculino , Humanos , Adulto Jovem , Adulto , Espaço Parafaríngeo/cirurgia , Faringe/cirurgia , Hemiplegia , Estudos Retrospectivos , Neurilemoma/complicações , Neurilemoma/cirurgia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia
16.
J Org Chem ; 88(13): 8955-8968, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37294694

RESUMO

The acceptorless dehydrogenative coupling (ADC) between alcohols and amines to produce imines has been achieved mostly by employing precious-metal-based complexes or complexes of earth-abundant metal ions with sensitive and complicated ligand systems as catalysts mostly under harsh reaction conditions. Methodologies using readily available earth-abundant metal salts as catalysts without the requirement of ligand, oxidant, or any external additives are not explored. We report an unprecedented microwave-assisted CoCl2-catalyzed acceptorless dehydrogenative coupling of benzyl alcohol and amine for the synthesis of E-aldimines, N-heterocycles, and H2 under mild condition, without any complicated exogenous ligand template, oxidant, or other additives. This environmentally benign methodology exhibits broad substrate scope (43 including 7 new products) with fair functional-group tolerance on the aniline ring. Detection of metal-associated intermediate by gas chromatography (GC) and HRMS, H2 detection by GC, and kinetic isotope effect reveal the mechanism of this CoCl2-catalyzed reaction to be via ADC. Furthermore, kinetic experiments and Hammett analysis with variation in the nature of substituents over the aniline ring reveal the insight into the reaction mechanism with different substituents.


Assuntos
Álcool Benzílico , Complexos de Coordenação , Ligantes , Micro-Ondas , Compostos de Anilina , Aminas , Oxidantes
17.
Artigo em Inglês | MEDLINE | ID: mdl-37166647

RESUMO

Actinomycetes are considered a never-ending treasure trove of biometabolites, which always fascinated researchers. However, to combat with newly emerging bacterial strains, the search for novel or analogs of existing therapeutic agents is recommended. In this context, this research work was carried out to search for a biopotent Actinomycetal strain grown in untapped soil, near the Hirakud dam. This Gram-positive bacteria was subjected to screening for its bioactivity against the medically important bacteria, isolated from local hospital sample using "co-culture" method, following both qualitative and quantitative assays. Further, the 16 s rRNA sequencing, BLASTn analysis, and GC% calculation were carried out. Based upon its bioactivity, a prediction-based genomics work was pursued, considering the gene sequence deposited in public domain. The reverse translation, elution of protein structural file, and the putative protein were predicted. The strain was identified as Microbacterium barkeri, with 54.1% GC content. From Gene Ontology term annotation, it was predicted that the α/ß hydrolase fold of hydrolase protein could have been responsible for antibiotic/biometabolite synthesis, in silico. The in vitro-based sequence (from Whole Genome Sequence data) had inferred that there was elution of alpha/beta hydrolase fold, substantiated with conserved domain analysis, ORF finding more over Gene Ontology (GO) terminology annotations. The GO annotations had suggested that the protein had been produced in response to a bacteria, under the influence of external stimuli more so in stress.

18.
Epilepsia ; 64(8): 2014-2026, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37129087

RESUMO

OBJECTIVE: The accurate prediction of seizure freedom after epilepsy surgery remains challenging. We investigated if (1) training more complex models, (2) recruiting larger sample sizes, or (3) using data-driven selection of clinical predictors would improve our ability to predict postoperative seizure outcome using clinical features. We also conducted the first substantial external validation of a machine learning model trained to predict postoperative seizure outcome. METHODS: We performed a retrospective cohort study of 797 children who had undergone resective or disconnective epilepsy surgery at a tertiary center. We extracted patient information from medical records and trained three models-a logistic regression, a multilayer perceptron, and an XGBoost model-to predict 1-year postoperative seizure outcome on our data set. We evaluated the performance of a recently published XGBoost model on the same patients. We further investigated the impact of sample size on model performance, using learning curve analysis to estimate performance at samples up to N = 2000. Finally, we examined the impact of predictor selection on model performance. RESULTS: Our logistic regression achieved an accuracy of 72% (95% confidence interval [CI] = 68%-75%, area under the curve [AUC] = .72), whereas our multilayer perceptron and XGBoost both achieved accuracies of 71% (95% CIMLP = 67%-74%, AUCMLP = .70; 95% CIXGBoost own = 68%-75%, AUCXGBoost own = .70). There was no significant difference in performance between our three models (all p > .4) and they all performed better than the external XGBoost, which achieved an accuracy of 63% (95% CI = 59%-67%, AUC = .62; pLR = .005, pMLP = .01, pXGBoost own = .01) on our data. All models showed improved performance with increasing sample size, but limited improvements beyond our current sample. The best model performance was achieved with data-driven feature selection. SIGNIFICANCE: We show that neither the deployment of complex machine learning models nor the assembly of thousands of patients alone is likely to generate significant improvements in our ability to predict postoperative seizure freedom. We instead propose that improved feature selection alongside collaboration, data standardization, and model sharing is required to advance the field.


Assuntos
Epilepsia , Criança , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Epilepsia/diagnóstico , Epilepsia/cirurgia , Convulsões/diagnóstico , Convulsões/cirurgia , Aprendizado de Máquina
19.
Indian J Otolaryngol Head Neck Surg ; 75(1): 21-31, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37007879

RESUMO

To evaluate the outcomes in patients of vascular tinnitus managed at our institute. The clinical data of all patients diagnosed with pulsatile tinnitus from January 2014 to April 2022 and managed at AIIMS, Bhubaneswar, was retrospectively reviewed. The diagnosis, treatment and outcomes were analyzed. A 6-year literature review was performed from March 2015 to April 2021. Our series discusses managing eleven cases of vascular tinnitus with varied aetiology and their outcomes. Out of the eleven cases, eight patients underwent surgical or radiological intervention, and seven had complete resolution of symptoms. Of the eleven patients, three had partial resolution. The 6-year literature review revealed sigmoid and transverse sinus as the most common causative anatomical sites for pulsatile tinnitus. Amongst those who received an intervention, 83.56% of the patients had complete resolution of symptoms. Vascular tinnitus can be cured if the exact vessel causing it is localized. Clinical suspicion is based on the character of tinnitus and patient history. A careful evaluation of the head and neck sites for any vascular anomaly that can cause pulsatile tinnitus must be done. Radiology demonstrates treatable causes of it. It delineates the aberrant anatomical variations that can lead to this disturbing aetiology. Treatable causes are best addressed, and pathology should be taken care of. A multidisciplinary team comprising ENT surgeons, audiologists and interventional radiologists must identify and treat the pathology.

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