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1.
Proc Natl Acad Sci U S A ; 120(52): e2300842120, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38127979

RESUMO

Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and diseases. The genetic underpinnings of these patterns remain largely unknown. We apply a stochastic multivariate factorization method to a diverse population of 50,699 individuals (12 studies and 130 sites) and derive data-driven, multi-scale PSCs of regional brain size. PSCs were significantly correlated with 915 genomic loci in the discovery set, 617 of which are newly identified, and 72% were independently replicated. Key pathways influencing PSCs involve reelin signaling, apoptosis, neurogenesis, and appendage development, while pathways of breast cancer indicate potential interplays between brain metastasis and PSCs associated with neurodegeneration and dementia. Using support vector machines, multi-scale PSCs effectively derive imaging signatures of several brain diseases. Our results elucidate genetic and biological underpinnings that influence structural covariance patterns in the human brain.


Assuntos
Neoplasias Encefálicas , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/patologia , Mapeamento Encefálico/métodos , Genômica , Neoplasias Encefálicas/patologia
2.
Photochem Photobiol Sci ; 23(2): 285-302, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38143251

RESUMO

Environmental variation has a significant impact on how organisms, including cyanobacteria, respond physiologically and biochemically. Salinity and ultraviolet radiation (UVR)-induced variations in the photopigments of the rice-field cyanobacterium Nostochopsis lobatus HKAR-21 and its photosynthetic performance was studied. We observed that excessive energy dissipation after UVR is mostly caused by Non-Photochemical Quenching (NPQ), whereas photochemical quenching is important for preventing photoinhibition. These findings suggest that ROS production may play an important role in the UVR-induced injury. To reduce ROS-induced oxidative stress, Nostochopsis lobatus HKAR-21 induces the effective antioxidant systems, which includes different antioxidant compounds like carotenoids and enzymes such as superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX). The study indicates that Nostochopsis lobatus HKAR-21 exposed to photosynthetically active radiation + UV-A + UV-B (PAB) and PAB + NaCl (PABN) had significantly reduced photosynthetic efficiency. Furthermore, maximum ROS was detected in PAB exposed cyanobacterial cells. The induction of lipid peroxidation (LPO) has been investigated to evaluate the impact of UVR on the cyanobacterial membrane in addition to enzymatic defensive systems. The maximal LPO level was found in PABN treated cells. Based on the findings of this research, it was concluded that salinity and UVR had collegial effects on the major macromolecular components of the rice-field cyanobacterium Nostochopsis lobatus HKAR-21.


Assuntos
Cianobactérias , Oryza , Raios Ultravioleta , Antioxidantes/farmacologia , Oryza/efeitos da radiação , Cloreto de Sódio/farmacologia , Espécies Reativas de Oxigênio , Cianobactérias/metabolismo , Fotossíntese/efeitos da radiação , Superóxido Dismutase/metabolismo
3.
Health Qual Life Outcomes ; 22(1): 26, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481231

RESUMO

BACKGROUND: Cancer survivors experience a decrement in health-related quality of life (HRQoL) resulting from the disease as well as adverse effects of therapy. We evaluated the HRQoL of cancer patients, stratified by primary cancer site, stage, treatment response and associated adverse events, along with its determinants. METHODS: Data were collected from 12,148 patients, sampled from seven purposively chosen leading cancer hospitals in India, to elicit HRQoL using the EuroQol questionnaire comprising of 5-dimensions and 5-levels (EQ-5D-5L). Multiple linear regression was used to determine the association between HRQoL and various socio-demographic as well as clinical characteristics. RESULTS: Majority outpatients (78.4%) and inpatients (81.2%) had solid cancers. The disease was found to be more prevalent among outpatients (37.5%) and inpatients (40.5%) aged 45-60 years and females (49.3-58.3%). Most patients were found to be in stage III (40-40.6%) or stage IV (29.4-37.3%) at the time of recruitment. The mean EQ-5D-5 L utility score was significantly higher among outpatients [0.630 (95% CI: 0.623, 0.637)] as compared to inpatients [0.553 (95% CI: 0.539, 0.567)]. The HRQoL decreased with advancing cancer stage among both inpatients and outpatients, respectively [stage IV: (0.516 & 0.557); stage III (0.609 & 0.689); stage II (0.677 & 0.713); stage I (0.638 & 0.748), p value < 0.001]. The outpatients on hormone therapy (B = 0.076) showed significantly better HRQoL in comparison to patients on chemotherapy. However, palliative care (B=-0.137) and surgery (B=-0.110) were found to be associated with significantly with poorer HRQoL paralleled to chemotherapy. The utility scores among outpatients ranged from 0.305 (bone cancer) to 0.782 (Leukemia). Among hospitalized cases, the utility score was lowest for multiple myeloma (0.255) and highest for testicular cancer (0.771). CONCLUSION: Older age, lower educational status, chemotherapy, palliative care and surgery, advanced cancer stage and progressive disease were associated with poor HRQoL. Our study findings will be useful in optimising patient care, formulating individualized treatment plan, improving compliance and follow-up.


Assuntos
Mieloma Múltiplo , Neoplasias Testiculares , Masculino , Feminino , Humanos , Qualidade de Vida , Inquéritos e Questionários , Escolaridade
4.
J Chem Phys ; 160(2)2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38193555

RESUMO

We present a comprehensive study using dissipative particle dynamics simulations to investigate phase separation kinetics (PSK) in three-dimensional (3d) polymeric fluids under random photo-illumination. We consider two scenarios: polymer blends with active radicals at one end of each immiscible chain and block copolymer (BCP) melts with photosensitive bonds linking incompatible blocks. The phase separation (PS) is induced by temperature quench of the initial homogeneously mixed system. Simultaneously, the system experiences random photo-illumination, simulated by two concurrent random events: (a) the recombination of active radicals in polymer blends and (b) the breaking of photosensitive bonds in BCP chains. Variations in the bond-breaking probability, Pb, mimic the change in light intensity. The length scale follows power law growth, R(t) ∼ tϕ, where ϕ represents the growth exponent. Increasing Pb results in a gradual transition in growth kinetics from micro-PS to macro-PS, accompanied by corresponding transition probabilities for both systems. Micro-PSK dominates the evolution process at low Pb values. The scaling functions exhibit data overlap for most scaled distances, indicating the statistical self-similarity of evolving patterns. Our study enhances the understanding of PSK in polymeric fluids, revealing the impact of photosensitive bonds and active radicals. Furthermore, it suggests the potential for designing novel polymeric materials with desired properties.

5.
J Biosoc Sci ; 56(2): 338-356, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37987163

RESUMO

In India, undernutrition among children has been extremely critical for the last few decades. Most analyses of undernutrition among Indian children have used the administrative boundaries of a state or a district level as a unit of analysis. This paper departs from such a practice and focuses instead on the political boundaries of a parliamentary constituency (PC) as the unit of analysis. The PC is a critical geopolitical unit where political parties and party candidates make election promises and implement programmes to improve the socio-economic condition of their electorate. A focus on child undernutrition at this level has the potential for greater policy and political traction and could lead to a paradigm shift in the strategy to tackle the problem by creating a demand for political accountability. Different dimensions and new approaches are also required to evaluate the socio-economic status and generate concrete evidence to find solutions to the problem. Given the significance of advanced analytical methods and models embedded into geographic information system (GIS), the current study, for the first time, uses GIS tools and techniques at the PC level, conducting in-depth analysis of undernutrition and its predictors. Hence, this paper examines the spatial heterogeneity in undernutrition across PCs by using geospatial techniques such as univariate and bivariate local indicator of spatial association and spatial regression models. The analysis highlights the high-low burden areas in terms of local hotspots and identifies the potential spatial risk factors of undernutrition across the constituencies. Striking variations in the prevalence of undernutrition across the constituencies were observed. Most of these constituencies that performed poorly both in terms of child nutrition and socio-economic indicators were located in the northern, western, and eastern parts of India. A statistically significant association of biological, socio-economic, and environmental factors such as women's body mass index, anaemia in children, poverty, household sanitation facilities, and institutional births was established. The results highlight the need to bring in a mechanism of political accountability that directly connects elected representatives to maternal and child health outcomes. The spatial variability and pattern of undernutrition indicators and their correlates indicate that priority setting in research may also be greatly influenced by the neighbourhood association.


Assuntos
Desnutrição , Criança , Humanos , Feminino , Lactente , Desnutrição/epidemiologia , Pobreza , Características da Família , Fenômenos Fisiológicos da Nutrição Infantil , Índia/epidemiologia
6.
Ergonomics ; : 1-17, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38192115

RESUMO

The cross-sectional study aimed to investigate the relationship between work-related factors, perceived work fatigue (PWF) and musculoskeletal disorders (MSDs) among handicraft artisans. 364 artisans participated in a questionnaire survey, and a structural equation model (SEM) was developed to explore the direct and indirect relationships between these factors using partial least squares analysis. The SEM explained 98.2% of the variance in MSDs and revealed that exposure to biomechanical factors had a direct impact on PWF and MSDs, with PWF mediating the effect of biomechanical factors on MSDs. Additionally, job demand was found to be positively associated with MSDs, while job control and social support reduced the risk of MSDs. The findings underscore the importance of strategic initiatives to mitigate the risk of developing MSDs among artisans. The study also highlights the potential of SEM as a novel framework for understanding the complex pathogenesis of MSDs in occupational health research.Practitioner summary: The study sought to comprehensively examine the intricate relationships among work-related factors, PWF, and MSDs. To achieve this, an SEM approach was employed to capture both direct and indirect relationships between these factors, employing partial least squares analysis. Findings revealed SEM as an innovative framework for understanding the intricate development of MSDs.

7.
J Nematol ; 56(1): 20240007, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38510971

RESUMO

Anguina tritici, the wheat seed gall nematode, causes the 'ear-cockle' or seed gall disease of wheat (Triticum sp.), leading to an extensive decline of yield (30-70%) in underdeveloped wheat cultivating countries of the world. The nematode is known to survive in anhydrobiotic conditions for up to 32 years. Here, we present the first transcriptome assembly of A. tritici, which will be a valuable resource for understanding the genes responsible for nematode survival and above-ground plant parasitism. The final 133.2 Mb assembly consists of 105606 open reading frames (including isoforms) with the following BUSCO scores against Nematoda database: 80.3% complete (16.4% single copy and 63.9% duplicated), 2.1% fragmented, and 17.6% missing.

8.
BMC Oral Health ; 24(1): 219, 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38342887

RESUMO

BACKGROUND: This study was conducted to assess the prevalence of dental caries, tobacco usage, and associated risk factors for dental caries in patients who visited a government hospital in Western, Nepal. METHODS: This analytical cross-sectional study was conducted from January to April 2022. Patients above 18 years visiting the dental OPD of a government hospital, and who had provided informed consent were enrolled in the study using a convenience sampling technique. As the study also involved an illiterate population, in that case, informed consent was obtained from their respective legal guardian as well. A pretested standardized, close-ended questionnaire was administered by researchers to gather information regarding the associated risk factors and oral hygiene practices. Clinical examination was done for dental caries according to the criteria by the World Health Organization (WHO) using the "DMFT" index (WHO modification 1987). Bivariate and multivariable logistic regression was done and the odds ratio and p-value was calculated. For all tests, statistical significance was set at p < 0.05. RESULTS: A total of 219 participants completed the study with a mean age of 31.73 ± 12.46. The prevalence of dental caries and tobacco was found to be 80.36% and 5.02% respectively. Participants without health insurance had 2.35 times higher odds of dental caries (95% CI: 1.03-5.36). Not rinsing the mouth after eating sweets was associated with 3.07 times higher odds of dental caries (95% CI: 1.31-7.18). Those who hadn't visited a dentist in the past 12 months had lower odds (0.42; 95% CI: 0.18-0.94). Eating fresh fruit daily showed statistically higher odds (2.70; 95% CI: 1.04-6.99) of dental caries. Non-tobacco users had higher odds (14.19; 2.55-78.99) of dental caries. CONCLUSION: Dental caries is highly prevalent, while tobacco usage is relatively low. Factors associated with dental caries included lack of health insurance coverage, consumption of fruits once daily, recent dental visits within the past year, not rinsing the mouth with water after consuming sweets, and non-tobacco users.


Assuntos
Cárie Dentária , Humanos , Adulto Jovem , Adulto , Cárie Dentária/epidemiologia , Cárie Dentária/etiologia , Estudos Transversais , Nepal/epidemiologia , Índice CPO , Fatores de Risco , Prevalência , Governo , Hospitais , Produtos do Tabaco
9.
Angew Chem Int Ed Engl ; 63(28): e202403093, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38679566

RESUMO

The synthesis of covalent organic frameworks (COFs) at bulk scale require robust, straightforward, and cost-effective techniques. However, the traditional solvothermal synthetic methods of COFs suffer low scalability as well as requirement of sensitive reaction environment and multiday reaction time (2-10 days) which greatly restricts their practical application. Here, we report microwave assisted rapid and optimized synthesis of a donor-acceptor (D-A) based highly crystalline COF, TzPm-COF in second (10 sec) to minute (10 min) time scale. With increasing the reaction time from seconds to minutes crystallinity, porosity and morphological changes are observed for TzPm-COF. Owing to visible range light absorption, suitable band alignment, and low exciton binding energy (Eb=64.6 meV), TzPm-COF can efficaciously produce superoxide radical anion (O2 .-) after activating molecular oxygen (O2) which eventually drives aerobic photooxidative amidation reaction with high recyclability. This photocatalytic approach works well with a variety of substituted aromatic aldehydes having electron-withdrawing or donating groups and cyclic, acyclic, primary or secondary amines with moderate to high yield. Furthermore, catalytic mechanism was established by monitoring the real-time reaction progress through in situ diffuse reflectance infrared Fourier transform spectroscopic (DRIFTS) study.

10.
J Food Sci Technol ; 61(3): 503-515, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38327858

RESUMO

Goat milk has achieved significant place in human diet owing to its enormous therapeutic properties. There exists a scope of value-addition of goat milk to potentiate its health benefits by incorporating herbs and plants. Giloy (Tinospora cordifolia), a traditional medicinal plant with rich bioactive composition, can enhance the bioactive properties and shelf-life of goat milk. To this end, a study was conducted to develop shelf-stable giloy-goat milk beverage (GGB) by adding debittered giloy juice to goat milk (GM) and analyse the detailed product profile including proximate composition, bioactive properties, sensory, rheological, and structural characterisation. GGB resulted in two-fold increase (P < 0.05) in antioxidant activity and total phenolic content, thus enhancing the bioactive properties of the beverage as compared to GM. Further, increase in the particle size of GGB was observed along with components interaction, which was confirmed by FTIR, scanning electron and fluorescent microscopy. Storage stability studies indicated that bioactive properties of GGB remained unaffected (P > 0.05) by the sterilization process up to 90 days and sensory characteristics were not compromised till 105 days of storage. Therefore, the developed GGB is considered to be a shelf-stable beverage that retains its bioactive and sensory properties even after sterilization, making it a promising functional dairy product.

11.
Indian J Urol ; 40(2): 112-120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725891

RESUMO

Introduction: Chemotherapy, postchemotherapy retroperitoneal lymph node dissection (pcRPLND), and metastasectomy remain the standard of care for the management of advanced nonseminomatous germ cell tumor (NSGCT). Methods: We retrospectively studied 73 patients who had pcRPLND at a single tertiary-care center (2003-2022). Surgical and clinicopathological features and oncological outcomes are presented. Results: The mean age was 28.27 years (15-48). Three-fourths had Stage III disease at diagnosis. International Germ Cell Cancer Collaborative Group risk stratification was 54.54% and 21.21% in intermediate risk, and poor risk, respectively. Sixty-two patients had Standard, 7 had Salvage and 4 underwent Desperation pcRPLND. Eleven patients (15.06%) required adjunctive procedures. Thirteen patients (17.8%) had ≥ class 3 Clavien-Dindo complications and postoperative mortality occurred in 5 (6.8%) patients. The histopathologies (HPE) of the pcRPLNDs were necrosis, teratoma, and viable tumor in 39.7%, 45.2%, and 15.1%, respectively. Seven patients underwent metastasectomy. An 85% size reduction in the size of RPLN predicted necrosis. There was 71.4% concordance between pcRPLND and metastasectomy HPEs. The median follow-up was 26.72 months (inter-quartile range - 13.25-47.84). The 2-year recurrence-free survival (RFS) rate was 93% (95% confidence interval [CI]-83%-97%) and the overall survival (OS) rate was 90% (95% CI-80%-95%). This is the largest series of pcRPLND for NSGCT in India to our knowledge. Conclusion: Although most of the cohort belonged to stage III, an RFS and OS rate of >90% at 2 years was achieved. We believe that successful management of postchemotherapy residual masses in NSGCT is contingent on the availability of multidisciplinary expertise and is therefore best done at tertiary-care referral centers.

12.
J Biol Chem ; 298(9): 102352, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35940306

RESUMO

Drug resistance by pathogenic microbes has emerged as a matter of great concern to mankind. Microorganisms such as bacteria and fungi employ multiple defense mechanisms against drugs and the host immune system. A major line of microbial defense is the biofilm, which comprises extracellular polymeric substances that are produced by the population of microorganisms. Around 80% of chronic bacterial infections are associated with biofilms. The presence of biofilms can increase the necessity of doses of certain antibiotics up to 1000-fold to combat infection. Thus, there is an urgent need for strategies to eradicate biofilms. Although a few physicochemical methods have been developed to prevent and treat biofilms, these methods have poor efficacy and biocompatibility. In this review, we discuss the existing strategies to combat biofilms and their challenges. Subsequently, we spotlight the potential of enzymes, in particular, polysaccharide degrading enzymes, for biofilm dispersion, which might lead to facile antimicrobial treatment of biofilm-associated infections.


Assuntos
Anti-Infecciosos , Biofilmes , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Polissacarídeos
13.
Mol Genet Genomics ; 298(3): 555-566, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36856825

RESUMO

The cancer syndrome polymerase proofreading-associated polyposis results from germline mutations in the POLE and POLD1 genes. Mutations in the exonuclease domain of these genes are associated with hyper- and ultra-mutated tumors with a predominance of base substitutions resulting from faulty proofreading during DNA replication. When a new variant is identified by gene testing of POLE and POLD1, it is important to verify whether the variant is associated with PPAP or not, to guide genetic counseling of mutation carriers. In 2015, we reported the likely pathogenic (class 4) germline POLE c.1373A > T p.(Tyr458Phe) variant and we have now characterized this variant to verify that it is a class 5 pathogenic variant. For this purpose, we investigated (1) mutator phenotype in tumors from two carriers, (2) mutation frequency in cell-based mutagenesis assays, and (3) structural consequences based on protein modeling. Whole-exome sequencing of two tumors identified an ultra-mutator phenotype with a predominance of base substitutions, the majority of which are C > T. A SupF mutagenesis assay revealed increased mutation frequency in cells overexpressing the variant of interest as well as in isogenic cells encoding the variant. Moreover, exonuclease repair yeast-based assay supported defect in proofreading activity. Lastly, we present a homology model of human POLE to demonstrate structural consequences leading to pathogenic impact of the p.(Tyr458Phe) mutation. The three lines of evidence, taken together with updated co-segregation and previously published data, allow the germline variant POLE c.1373A > T p.(Tyr458Phe) to be reclassified as a class 5 variant. That means the variant is associated with PPAP.


Assuntos
DNA Polimerase II , Neoplasias , Humanos , DNA Polimerase II/genética , DNA Polimerase II/química , DNA Polimerase II/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/genética , Neoplasias/genética , Mutação , Exonucleases/genética , Exonucleases/metabolismo
14.
Small ; 19(14): e2206063, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36624578

RESUMO

Zinc oxide (ZnO) is a thermally stable n-type semiconducting material. ZnO 2D nanosheets have mainly gained substantial attention due to their unique properties, such as direct bandgap and strong excitonic binding energy at room temperature. These are widely utilized in piezotronics, energy storage, photodetectors, light-emitting diodes, solar cells, gas sensors, and photocatalysis. Notably, the chemical properties and performances of ZnO nanosheets largely depend on the nano-structuring that can be regulated and controlled through modulating synthetic strategies. Two synthetic approaches, top-down and bottom-up, are mainly employed for preparing ZnO 2D nanomaterials. However, owing to better results in producing defect-free nanostructures, homogenous chemical composition, etc., the bottom-up approach is extensively used compared to the top-down method for preparing ZnO 2D nanosheets. This review presents a comprehensive study on designing and developing 2D ZnO nanomaterials, followed by accenting its potential applications. To begin with, various synthetic strategies and attributes of ZnO 2D nanosheets are discussed, followed by focusing on methodologies and reaction mechanisms. Then, their deliberation toward batteries, supercapacitors, electronics/optoelectronics, photocatalysis, sensing, and piezoelectronic platforms are further discussed. Finally, the challenges and future opportunities are featured based on its current development.

15.
Cancer Invest ; 41(9): 789-802, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37909664

RESUMO

We assessed the efficacy, tolerability, and cost-effectiveness of a novel neoadjuvant regimen comprising docetaxel-cyclophosphamide alternating with epirubicin-cisplatin (ddDCEP) administered biweekly for 16 weeks in 116 patients with early triple-negative breast cancer. This regimen achieved a high pathological complete response (ypT0/TisN0) rate of 55.2% and favorable survival outcomes (30-month event-free survival, 91.2%; overall survival, 97%). Febrile neutropenia was observed in 4.3% of patients, and 98% completed at least six of eight cycles. ddDCEP was more cost-effective than contemporary carboplatin-based regimens. This novel approach offers an economically viable and effective alternative to current chemoimmunotherapy regimens, and merits further investigation.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Docetaxel/uso terapêutico , Epirubicina/uso terapêutico , Cisplatino/efeitos adversos , Platina/uso terapêutico , Neoplasias de Mama Triplo Negativas/patologia , Taxoides/efeitos adversos , Resultado do Tratamento , Ciclofosfamida/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Neoadjuvante
16.
BMC Psychiatry ; 23(1): 59, 2023 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690972

RESUMO

BACKGROUND: Efforts to develop neuroimaging-based biomarkers in major depressive disorder (MDD), at the individual level, have been limited to date. As diagnostic criteria are currently symptom-based, MDD is conceptualized as a disorder rather than a disease with a known etiology; further, neural measures are often confounded by medication status and heterogeneous symptom states. METHODS: We describe a consortium to quantify neuroanatomical and neurofunctional heterogeneity via the dimensions of novel multivariate coordinate system (COORDINATE-MDD). Utilizing imaging harmonization and machine learning methods in a large cohort of medication-free, deeply phenotyped MDD participants, patterns of brain alteration are defined in replicable and neurobiologically-based dimensions and offer the potential to predict treatment response at the individual level. International datasets are being shared from multi-ethnic community populations, first episode and recurrent MDD, which are medication-free, in a current depressive episode with prospective longitudinal treatment outcomes and in remission. Neuroimaging data consist of de-identified, individual, structural MRI and resting-state functional MRI with additional positron emission tomography (PET) data at specific sites. State-of-the-art analytic methods include automated image processing for extraction of anatomical and functional imaging variables, statistical harmonization of imaging variables to account for site and scanner variations, and semi-supervised machine learning methods that identify dominant patterns associated with MDD from neural structure and function in healthy participants. RESULTS: We are applying an iterative process by defining the neural dimensions that characterise deeply phenotyped samples and then testing the dimensions in novel samples to assess specificity and reliability. Crucially, we aim to use machine learning methods to identify novel predictors of treatment response based on prospective longitudinal treatment outcome data, and we can externally validate the dimensions in fully independent sites. CONCLUSION: We describe the consortium, imaging protocols and analytics using preliminary results. Our findings thus far demonstrate how datasets across many sites can be harmonized and constructively pooled to enable execution of this large-scale project.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Encéfalo , Neuroimagem , Imageamento por Ressonância Magnética/métodos , Inteligência Artificial
17.
Nephrology (Carlton) ; 28(1): 60-71, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36217796

RESUMO

AIM: Podocytes, a vital component of the glomerular filtration barrier, are vulnerable to various noxious stimuli, including Hypoxic. HIF1α that transduces hypoxic adaptations induces Transglutaminase 2 (TG2), which catalyses cross-linking of extracellular matrix proteins. In this study, we investigated the mechanism of regulation of TG2 by HIF1α. METHODS: HIF1α was induced in podocytes by treating with FG4592 (Roxadustat) or hypoxia (1% oxygen) and in mice by treating with FG4592. Gene expression and protein analysis of ZEB2, TRPC6 and TG2 were performed in both experimental models. Histological and kidney function analyses were performed in mice. RESULTS: Data mining revealed co-expression of HIF1α, ZEB2, TRPC6 and TG2 in the chronic kidney diseases (CKD)-validated dataset. We observed elevated expression of ZEB2, TRPC6 and TG2 in FG4592-treated podocytes. Ectopic expression of ZEB2 resulted in high TRPC6 expression, elevated intracellular calcium levels and increased TG2 activity. Blocking the TRPC6 channel or inhibiting its expression partially attenuated FG4592-induced TG2 activity, whereas suppression of ZEB2 expression significantly abolished TG2 activity. Furthermore, we noticed the induction of the ZEB2/TRPC6/TG2 axis in podocytes in mice administered with FG-4592. Metformin ameliorated the HIF1α-induced podocyte injury and proteinuria in mice administered with FG-4592. CONCLUSION: This study demonstrates that HIF1α stimulates both TG2 expression and activity via ZEB2/TRPC6 axis, whereas abrogation of HIF1α by metformin prevented hypoxia-induced glomerular injury. Metformin could be explored to treat proteinuric diseases such as CKD, sleep apnea and renal Ischemia-reperfusion-injury, where hypoxia is considered a risk factor.


Assuntos
Metformina , Podócitos , Insuficiência Renal Crônica , Camundongos , Animais , Podócitos/metabolismo , Canal de Cátion TRPC6/genética , Canal de Cátion TRPC6/metabolismo , Metformina/farmacologia , Proteína 2 Glutamina gama-Glutamiltransferase , Canais de Cátion TRPC/genética , Canais de Cátion TRPC/metabolismo , Hipóxia/complicações , Hipóxia/metabolismo , Hipóxia/patologia , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/prevenção & controle , Insuficiência Renal Crônica/metabolismo
18.
J Dairy Res ; 90(2): 205-212, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37264806

RESUMO

Eggnog, a dairy-based beverage, comprises both milk and egg proteins. We aimed at optimizing the eggnog formulation using Box-Behnken design of response surface methodology. The combined effects of milk (60-75), cream (25-35) and eggnog base (6-8, all three as g 100/ml) were investigated on heat coagulation time, viscosity and thermal gelation temperature. ANOVA indicated that experimental data were well explained by a quadratic model with high check values (R2 > 0.94) and non-significant lack of fit tests. Based on the responses, an optimized formulation of eggnog with 60.0 milk, 25.0 cream and 6.50 eggnog base (as g 100/ml), could be considered best for manufacturing eggnog with desired attributes. This optimized formulation was characterized for physico-chemical, microbial and sensory attributes and the results indicated significantly higher fat and protein content than control formulation, but lesser lactose and total sugar content. Significantly higher viscosity, heat stability and lower thermal gelation temperature were also observed for the optimized formulation. Coliform, yeast and mold, E. coli and Salmonella counts were not detected in any sample but a significantly lower total plate count was observed for the optimized formulation.


Assuntos
Escherichia coli , Leite , Animais , Leite/química , Temperatura , Bebidas/análise , Temperatura Alta
19.
J Basic Microbiol ; 63(3-4): 359-376, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36453555

RESUMO

Despite the ubiquity of the genus Citrobacter in clinical, industrial, and environmental scenarios, a large number of Citrobacter strains have not been explored at the genome-scale level. In this study, accurate taxonomic assignment of strain AAK_AS5 isolated from activated sludge was achieved by in-silico genomic comparison using Overall Genome-based Relatedness Indices (ANI(OAT): 97.55%, ANIb:97.28%, and ANIm: 97.83%) that indicated its closest identity to the related strain Citrobacter portucalensis A60T . Results were consistent with a digital DNA-DNA hybridization value of 80% with C. portucalensis A60T which was greater than the species boundary value >70% for delineating closely related bacterial species. Gene mining through Kyoto Encyclopedia of Genes and Genomes (KEGG), and annotation using rapid annotation subsystem technology (RAST) revealed the notable gene contents for nitrogen metabolism and other pathways associated with nitrate/nitrite ammonification (28 genes), ammonia assimilation (22 genes), and denitrification pathways (14 genes). Furthermore, the strain AAK_AS5 also exhibited a high soluble chemical oxygen demand (sCOD), NH4 + -N, and NO3 - -N removal efficiency of 91.4%, 90%, and 93.6%, respectively thus validating its genetic capability for utilizing both (NH4 )2 SO4 and KNO3 as the nitrogen source. The study provided deeper insights into the phylogenomics and the genetic potential of Citrobacter, sp. strain AAK AS5 associated with nitrogen metabolism thus signifying the potential application of the isolate for treating nitrogen-rich wastewaters.


Assuntos
Desnitrificação , Nitrogênio , Filogenia , Citrobacter/genética , DNA
20.
Am J Orthod Dentofacial Orthop ; 164(5): 712-727, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37409990

RESUMO

INTRODUCTION: The increased use of social networking sites, such as Instagram (Meta Platforms, Menlo Park, Calif), has been silently affecting facial satisfaction among patients. However, the potential of Instagram to motivate participants for orthodontic treatment when used with an adjunct, a photograph editing software, is yet to be assessed. METHODS: From the initial 300 participants, 256 were included and randomly divided into an experimental group (participants were asked to provide their frontal smiling photograph) and a control group. The photographs received were corrected using photograph editing software and were shown along with other ideal smile photographs in an Instagram account to the experimental group, whereas the control group participants had access to only the ideal smile photographs. After browsing, the participants were given a modified version of the Malocclusion-Related Quality of Life Questionnaire. RESULTS: Questions assessing the general perception about one's smile, comparison with peers, desire to undergo orthodontic treatment, and the role of socioeconomic status showed a statistically significant difference (P <0.05) as most of the control group participants were unsatisfied with their teeth, had less desire to undergo orthodontic treatment and did not feel family's financial income to be a hurdle, contrary to the experimental group participants. A statistically significant difference (P <0.05) was also seen in assessing external acceptance, speech difficulties, and the influence of Instagram on orthodontic treatment, whereas the influence of photograph editing software did not show the same. CONCLUSIONS: The study concluded that the experimental group participants were motivated to undergo orthodontic treatment after viewing their corrected photograph.


Assuntos
Má Oclusão , Mídias Sociais , Humanos , Sorriso , Qualidade de Vida , Má Oclusão/terapia , Face , Estética Dentária
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