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1.
Acta Neurobiol Exp (Wars) ; 84(2): 136-152, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-39087840

RESUMO

Crossmodal correspondences (CMCs) refer to associations between seemingly arbitrary stimulus features in different sensory modalities. Pitch­size correspondences refer to the strong association of e.g., small objects with high pitches. Pitch­elevation correspondences refer to the strong association of e.g., visuospatial elevated objects with high pitches. We used functional magnetic resonance imaging (fMRI) to study the neural components, which underlie the CMCs in pitch­size and spatial pitch­elevation. This study focuses on answering the question of whether or not different CMCs are driven by similar neural mechanisms. The comparison of congruent against incongruent trials allows the estimation of CMC effects across different CMCs. The analysis of the measured neural activity in different CMCs strongly pointed toward different mechanisms which are involved in the processing of pitch­size and pitch­elevation correspondences. Differential, whole brain effects were observed within the superior parietal lobule (SPL), cerebellum and Heschls' gyrus (HG). Further, the angular gyrus (AnG), the intraparietal sulcus (IPS) and anterior cingulate cortex (ACC) were engaged in processing the CMCs but showed different effects for processing congruent compared to incongruent stimulus presentations. Within pitch­size significant effects in the AnG and ACC were found for congruent stimulus presentations whereas for pitch­elevation, significant effects in the ACC and IPS were found for incongruent stimulus presentations. In summary, the present results indicated differential neural processing in different simple audio­visual CMCs.


Assuntos
Estimulação Acústica , Mapeamento Encefálico , Encéfalo , Imageamento por Ressonância Magnética , Humanos , Masculino , Imageamento por Ressonância Magnética/métodos , Feminino , Adulto , Adulto Jovem , Estimulação Acústica/métodos , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Percepção da Altura Sonora/fisiologia , Estimulação Luminosa/métodos , Percepção Visual/fisiologia
2.
Health Aff (Millwood) ; 43(8): 1137-1146, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39102598

RESUMO

Nearly all patients with type 1 diabetes and 20-30 percent of patients with type 2 diabetes use insulin to manage glycemic control. Approximately one-quarter of patients who use insulin report underuse because of cost. In response, more than twenty states have implemented monthly caps on insulin out-of-pocket spending, ranging from $25 to $100. Using a difference-in-differences approach, this study evaluated whether state-level caps on insulin out-of-pocket spending change insulin usage among commercially insured enrollees. The study included 33,134 people ages 18-64 who had type 1 diabetes or who used insulin to manage type 2 diabetes with commercial insurance coverage that was subject to state-level oversight and was included in the 25 percent sample of the IQVIA PharMetrics database during 2018-21. Insulin out-of-pocket caps did not significantly increase quarterly insulin claims for enrollees who had type 1 diabetes or who used insulin to manage type 2 diabetes. State-level caps on insulin out-of-pocket spending for commercial enrollees did not significantly increase insulin use; that may be in part because of out-of-pocket expenses being lower than cap amounts.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Gastos em Saúde , Hipoglicemiantes , Insulina , Humanos , Insulina/uso terapêutico , Insulina/economia , Feminino , Pessoa de Meia-Idade , Adulto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/economia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/economia , Masculino , Estados Unidos , Gastos em Saúde/estatística & dados numéricos , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/economia , Adolescente , Revisão da Utilização de Seguros , Cobertura do Seguro/estatística & dados numéricos , Adulto Jovem , Seguro Saúde/economia , Seguro Saúde/estatística & dados numéricos , Custos de Medicamentos/estatística & dados numéricos
3.
Sci Rep ; 14(1): 19263, 2024 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164318

RESUMO

The interpretation of emotional facial expressions is crucial in everyday social interactions, and rapid processing of these expressions is necessary. Although extensive research has shed light on the mechanisms involved in facial expression processing, there is limited research on the potential role of the state of neural activity that directly precedes the occurrence of a face. Here, we investigated the potential modulatory role of pre-stimulus oscillatory activity in emotional facial expression processing. We tested emotional facial processing in two experiments, one utilizing artificial and the other natural facial expressions. The participants had to evaluate the emotional valence of the presented ambiguous facial expressions. In a univariate analysis, differences in the oscillation activity of the later rated valence of the faces were observed in both experiments, and these differences were observed even before the presentation of the facial expressions. Importantly, two different multivariate approaches directly supported the relevance of pre-stimulus oscillatory activity by exclusively using pre-stimulus oscillatory data to predict the perceived valence of the latter rated facial expression across the two experiments within as well as across subjects. The behavioral data shows the often observed negativity bias, i.e. ambiguous faces resulted in the tendency to rate them as negative. This negativity bias was related to neural activity modulations in the pre-stimulus period and also within post-stimulus processing related activity. These findings underscore the significance of pre-stimulus oscillatory activity in facial expression processing, indicating a functional role of ongoing neural states that affects the processing of facial expressions and constitute a basis for the well described negativity bias.


Assuntos
Emoções , Expressão Facial , Humanos , Emoções/fisiologia , Masculino , Feminino , Adulto , Adulto Jovem , Eletroencefalografia , Reconhecimento Facial/fisiologia , Estimulação Luminosa/métodos
4.
Chem Sci ; 15(29): 11455-11471, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39055015

RESUMO

We report the reactivity, structures and spectroscopic characterization of reactions of phosphine-based ligands (mono-, di- and tri-dentate) with iron-carbide carbonyl clusters. Historically, the archetype of this cluster class, namely [Fe6(µ6-C)(µ2-CO)4(CO)12]2-, can be prepared on a gram-scale but is resistant to simple ligand substitution reactions. This limitation has precluded the relevance of iron-carbide clusters relating to organometallics, catalysis and the nitrogenase active site cluster. Herein, we aimed to derive a simple and reliable method to accomplish CO → L (where L = phosphine or other general ligands) substitution reactions without harsh reagents or multi-step synthetic strategies. Ultimately, our goal was ligand-based chelation of an Fe n (µ n -C) core to achieve more synthetic control over multi-iron-carbide motifs relevant to the nitrogenase active site. We report that the key intermediate is the PSEPT-non-conforming cluster [Fe6(µ6-C)(CO)16] (2: 84 electrons), which can be generated in situ by the outer-sphere oxidation of [Fe6(µ6-C)(CO)16]2- (1: closo, 86 electrons) with 2 equiv. of [Fc]PF6. The reaction of 2 with excess PPh3 generates a singly substituted neutral cluster [Fe5(µ5-C)(CO)14PPh3] (4), similar to the reported reactivity of the substitutionally active cluster [Fe5(µ5-C)(CO)15] with monodentate phosphines (Cooke & Mays, 1990). In contrast, the reaction of 2 with flexible, bidentate phosphines (DPPE and DPPP) generates a wide range of unisolable products. However, the rigid bidentate phosphine bis(diphenylphosphino)benzene (bdpb) disproportionates the cluster into non-ligated Fe3-carbide anions paired with a bdpb-supported Fe(ii) cation, which co-crystallize in [Fe3(µ3-CH)(µ3-CO)(CO)9]2[Fe(MeCN)2(bdpb)2] (6). A successful reaction of 2 with the tripodal ligand Triphos generates the first multi-iron-chelated, authentic carbide cluster of the formula [Fe4(µ4-C)(κ3-Triphos)(CO)10] (9). DFT analysis of the key (oxidized) intermediate 2 suggests that its (µ6-C)Fe6 framework remains fully intact but is distorted into an axially compressed, 'ruffled' octahedron distinct from the parent closo cluster 1. Oxidation of the cluster in non-coordinating solvent allows for the isolation and crystallization of the CO-saturated, intact closo-analogue [Fe6(µ6-C)(CO)17] (3), indicating that the intact (µ6-C)Fe6 motif is retained during initial oxidation with [Fc]PF6. Overall, we demonstrate that redox modulation beneficially 'bends' Wade-Mingo's rules via the generation of electron-starved (non-PSEPT) intermediates, which are the key intermediates in promoting facile CO → L substitution reactions in iron-carbide-carbonyl clusters.

5.
Aesthet Surg J ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041862

RESUMO

BACKGROUND: The BODY-Q is a widely used patient-reported outcome measure for comprehensive assessment of treatment outcomes specific to patients undergoing body contouring surgery (BCS). However, for BODY-Q to be meaningfully interpreted and used in clinical practice, minimal important difference (MID) scores are needed. A MID is defined as the smallest change in outcome measure score that patients perceive important. OBJECTIVES: The aim of this study was to determine BODY-Q MID estimates for patients undergoing BCS to enhance the interpretability of the BODY-Q. METHODS: Data from an international, prospective cohort from Denmark, Finland, Germany, Italy, the Netherlands, and Poland were included. Two distribution-based methods were used to estimate MID: 0.2 standard deviations of mean baseline scores and the mean standardized response change of BODY-Q scores from baseline to 3 years postoperatively. RESULTS: A total of 12,554 assessments from 3,237 participants (mean age; 42.5±9.3 years; body mass index; 28.9±4.9 kg/m2) were included. Baseline MID scores ranged from 1 to 5 in the health-related quality of life (HRQL) scales and 3 to 6 in the appearance scales. The estimated MID scores from baseline to 3 years follow-up ranged from 4 to 5 in HRQL and from 4 to 8 in the appearance scales. CONCLUSIONS: The BODY-Q MID estimates from before BCS to 3 years postoperatively ranged from 4 to 8 and are recommended for use to interpret patients' BODY-Q scores, evaluate treatment effects of different BCS procedures, and for calculating sample size for future studies.

6.
J Am Chem Soc ; 146(28): 18989-18998, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38975810

RESUMO

For well-passivated semiconductor materials, the density of states (DOS) at the band edge determines the concentration of electrons (or holes) available to participate in photo/electrochemical redox and chemical reactions. Electrochemical impedance enables the characterization of photo-electrode DOS in a functional, in situ, electrochemical environment. However, the in situ electrochemical approach remains underutilized for band structure characterization of inorganic semiconductors. In this work, we demonstrate that the DOS of the well-passivated, highly ordered semiconductors silicon and germanium is directly probed by electrochemical impedance spectroscopy (EIS). More specifically, EIS measurements of the chemical capacitance in contact with electrolyte enable direct analysis of the DOS properties. From the capacitance-potential plot, the following parameters can be extracted: Fermi level, valence band maximum, conduction band minimum, and a quantitative value of the number of states at each potential. This study aims to establish the groundwork for future EIS investigations of electronically modified semiconductor interfaces with covalently bound organic molecules, organometallic catalysts, or more complex biorelated functionalizations.

7.
Environ Sci Technol ; 58(20): 8724-8735, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38717952

RESUMO

Building and protecting soil organic carbon (SOC) are critical to agricultural productivity, soil health, and climate change mitigation. We aim to understand how mechanisms at the organo-mineral interfaces influence SOC persistence in three contrasting soils (Luvisol, Vertisol, and Calcisol) under long-term free air CO2 enrichment conditions. A continuous wheat-field pea-canola rotation was maintained. For the first time, we provided evidence to a novel notion that persistent SOC is molecularly simple even under elevated CO2 conditions. We found that the elevated CO2 condition did not change the total SOC content or C forms compared with the soils under ambient CO2 as identified by synchrotron-based soft X-ray analyses. Furthermore, synchrotron-based infrared microspectroscopy confirmed a two-dimensional microscale distribution of similar and less diverse C forms in intact microaggregates under long-term elevated CO2 conditions. Strong correlations between the distribution of C forms and O-H groups of clays can explain the steady state of the total SOC content. However, the correlations between C forms and clay minerals were weakened in the coarse-textured Calcisol under long-term elevated CO2. Our findings suggested that we should emphasize identifying management practices that increase the physical protection of SOC instead of increasing complexity of C. Such information is valuable in developing more accurate C prediction models under elevated CO2 conditions and shift our thinking in developing management practices for maintaining and building SOC for better soil fertility and future environmental sustainability.


Assuntos
Dióxido de Carbono , Carbono , Solo , Dióxido de Carbono/química , Solo/química , Mudança Climática
8.
Inorg Chem ; 63(22): 10240-10250, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38758580

RESUMO

The use of new dynamic scaffolds for constructing inorganic and organometallic complexes with enhanced reactivities is an important new research direction. Toward this fundamental aim, an improved synthesis of the dynamic scaffold selenanthrene, along with its monoxide, trans-dioxide and the previously unknown trioxide, is reported. A discussion of the potential reaction mechanism for selenanthrene is provided, and all products were characterized using 1H, 13C, and 77Se nuclear magnetic resonance (NMR) spectroscopy and single-crystal X-ray crystallography. The dynamic ring inversion processes (i.e., "butterfly motion") for selenanthrene and its oxides were investigated using variable-temperature 1H NMR and density functional theory calculations. The findings suggest that selenanthrene possesses a roughly equal barrier to inversion as its sulfur analogue, thianthrene. However, selenanthrene oxides evidently possess larger inversion barriers as compared to their sulfur analogues due to the enhanced electrostatic intramolecular interactions inherent between the highly polar selenium-oxygen bond and adjacent C-H moieties. Finally, we propose a quantitative "flexibility index" in deg/(kcal/mol) for various tricyclic scaffolds to provide researchers with a comparative scale of dynamic motion across many different systems.

9.
Clin Infect Dis ; 79(2): 354-363, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-38690892

RESUMO

BACKGROUND: Metformin has antiviral activity against RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The mechanism appears to be suppression of protein translation via targeting the host mechanistic target of rapamycin pathway. In the COVID-OUT randomized trial for outpatient coronavirus disease 2019 (COVID-19), metformin reduced the odds of hospitalizations/death through 28 days by 58%, of emergency department visits/hospitalizations/death through 14 days by 42%, and of long COVID through 10 months by 42%. METHODS: COVID-OUT was a 2 × 3 randomized, placebo-controlled, double-blind trial that assessed metformin, fluvoxamine, and ivermectin; 999 participants self-collected anterior nasal swabs on day 1 (n = 945), day 5 (n = 871), and day 10 (n = 775). Viral load was quantified using reverse-transcription quantitative polymerase chain reaction. RESULTS: The mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (-0.56 log10 copies/mL; 95% confidence interval [CI], -1.05 to -.06; P = .027). Those who received metformin were less likely to have a detectable viral load than placebo at day 5 or day 10 (odds ratio [OR], 0.72; 95% CI, .55 to .94). Viral rebound, defined as a higher viral load at day 10 than day 5, was less frequent with metformin (3.28%) than placebo (5.95%; OR, 0.68; 95% CI, .36 to 1.29). The metformin effect was consistent across subgroups and increased over time. Neither ivermectin nor fluvoxamine showed effect over placebo. CONCLUSIONS: In this randomized, placebo-controlled trial of outpatient treatment of SARS-CoV-2, metformin significantly reduced SARS-CoV-2 viral load, which may explain the clinical benefits in this trial. Metformin is pleiotropic with other actions that are relevant to COVID-19 pathophysiology. CLINICAL TRIALS REGISTRATION: NCT04510194.


Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Metformina , SARS-CoV-2 , Carga Viral , Humanos , Metformina/uso terapêutico , Metformina/farmacologia , Carga Viral/efeitos dos fármacos , Masculino , SARS-CoV-2/efeitos dos fármacos , Feminino , Pessoa de Meia-Idade , Método Duplo-Cego , Antivirais/uso terapêutico , Antivirais/farmacologia , Adulto , COVID-19/virologia , Ivermectina/uso terapêutico , Ivermectina/farmacologia , Fluvoxamina/uso terapêutico , Fluvoxamina/farmacologia , Idoso
10.
BMJ Open ; 14(5): e082618, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38803255

RESUMO

OBJECTIVES: Researchers face numerous challenges when recruiting participants for health and social care research. This study reports on the challenges faced recruiting older adults for Being Your Best, a co-designed holistic intervention to manage and reduce frailty, and highlights lessons learnt amidst the COVID-19 pandemic. DESIGN: A qualitative study design was used. Referrer interviews were conducted to explore the recruitment challenges faced by the frontline workers. An audit of the research participant (aged ≥65) database was also undertaken to evaluate the reasons for refusal to participate and withdrawal from the study. SETTING: Hospital emergency departments (EDs) and a home care provider in Melbourne, Australia. PARTICIPANTS: Frontline workers and older adults. RESULTS: From May 2022 to June 2023, 71 referrals were received. Of those referrals, only 13 (18.3%) agreed to participate. Three participants withdrew immediately after baseline data collection, and the remaining 10 continued to participate in the programme. Reasons for older adult non-participation were (1) health issues (25.3%), (2) ineligibility (18.3%), (3) lack of interest (15.5%), (4) perceptions of being 'too old' (11.2%) and (5) perceptions of being too busy (5.6%). Of those participating, five were female and five were male. Eleven referrer interviews were conducted to explore challenges with recruitment, and three themes were generated after thematic analysis: (1) challenges arising from the COVID-19 pandemic, (2) characteristics of the programme and (3) health of older adults. CONCLUSION: Despite using multiple strategies, recruitment was much lower than anticipated. The ED staff were at capacity associated with pandemic-related activities. While EDs are important sources of participants for research, they were not suitable recruitment sites at the time of this study, due to COVID-19-related challenges. Programme screening characteristics and researchers' inability to develop rapport with potential participants also contributed to low recruitment numbers. TRIAL REGISTRATION NUMBER: ACTRN12620000533998; Pre-results.


Assuntos
COVID-19 , Fragilidade , Seleção de Pacientes , Pesquisa Qualitativa , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Idoso , Masculino , Feminino , Austrália/epidemiologia , Idoso de 80 Anos ou mais , Saúde Holística , Pandemias , Vitória , Idoso Fragilizado
12.
Sci Rep ; 14(1): 7895, 2024 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570599

RESUMO

A central aspect of episodic memory is the formation of associations between stimuli from different modalities. Current theoretical approaches assume a functional role of ongoing oscillatory power and phase in the theta band (3-7 Hz) for the encoding of crossmodal associations. Furthermore, ongoing activity in the theta range as well as alpha (8-12 Hz) and low beta activity (13-20 Hz) before the presentation of a stimulus is thought to modulate subsequent cognitive processing, including processes that are related to memory. In this study, we tested the hypothesis that pre-stimulus characteristics of low frequency activity are relevant for the successful formation of crossmodal memory. The experimental design that was used specifically allowed for the investigation of associative memory independent from individual item memory. Participants (n = 51) were required to memorize associations between audiovisual stimulus pairs and distinguish them from newly arranged ones consisting of the same single stimuli in the subsequent recognition task. Our results show significant differences in the state of pre-stimulus theta and alpha power between remembered and not remembered crossmodal associations, clearly relating increased power to successful recognition. These differences were positively correlated with memory performance, suggesting functional relevance for behavioral measures of associative memory. Further analysis revealed similar effects in the low beta frequency ranges, indicating the involvement of different pre-stimulus-related cognitive processes. Phase-based connectivity measures in the theta band did not differ between remembered and not remembered stimulus pairs. The findings support the assumed functional relevance of theta band oscillations for the formation of associative memory and demonstrate that an increase of theta as well as alpha band oscillations in the pre-stimulus period is beneficial for the establishment of crossmodal memory.


Assuntos
Memória Episódica , Humanos , Rememoração Mental , Reconhecimento Psicológico , Cognição , Ritmo Teta , Eletroencefalografia
13.
Mol Oncol ; 18(6): 1397-1416, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38429970

RESUMO

The effect of grainyhead-like transcription factor 3 (GRHL3) on cancer development depends on the cancer subtypes as shown in tumor entities such as colorectal or oral squamous cell carcinomas. Here, we analyzed the subtype-specific role of GRHL3 in bladder carcinogenesis, comparing common urothelial carcinoma (UC) with squamous bladder cancer (sq-BLCA). We examined GRHL3 mRNA and protein expression in cohorts of patient samples, its prognostic role and its functional impact on tumorigeneses in different molecular and histopathological subtypes of bladder cancer. We showed for GRHL3 a reverse expression in squamous and urothelial bladder cancer subtypes. Stably GRHL3-overexpressing EJ28, J82, and SCaBER in vitro models revealed a tumor-suppressive function in squamous and an oncogenic role in the urothelial cancer cells affecting cell and colony growth, and migratory and invasive capacities. Transcriptomic profiling demonstrated highly subtype-specific GRHL3-regulated expression networks coined by the enrichment of genes involved in integrin-mediated pathways. In SCaBER, loss of ras homolog family member A (RHOA) GTPase activity was demonstrated to be associated with co-regulation of eukaryotic translation initiation factor 4E family member 3 (EIF4E3), a potential tumor suppressor gene. Thus, our data provide for the first time a detailed insight into the role of the transcription factor GRHL3 in different histopathological subtypes of bladder cancer.


Assuntos
Carcinogênese , Proteínas de Ligação a DNA , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Humanos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Linhagem Celular Tumoral , Carcinogênese/genética , Carcinogênese/patologia , Feminino , Masculino , Proteína rhoA de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/genética , Movimento Celular/genética , Proliferação de Células/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Prognóstico , Fator de Iniciação 4E em Eucariotos/metabolismo , Fator de Iniciação 4E em Eucariotos/genética , Idoso
14.
J Am Chem Soc ; 146(9): 5735-5748, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38407043

RESUMO

Merging molecular bonding concepts with semiconductor- and materials-based concepts of band structure is challenging due to the mutually exclusive historical development and notations used in those respective fields: symmetry adapted linear combinations (SALCs) and Mulliken terms for molecules, versus k space and Bloch sums for materials. This lack of commonality brings the issue of hybridization (aka electronic coupling) between molecules and materials to the forefront in many aspects of modern chemical research─including nanocrystal properties, solar energy conversion, and molecular computing. It is thus critical to establish a holistic approach to hybridizing orbital (molecule) and plane-wave (semiconductor/material) systems to better describe symmetry-based molecule|material bonding and the corresponding symmetry-adapted molecular orbital (MO) diagrams. Such a unified approach would enable the construction of testable hypotheses about the role of symmetry and electronic structure in determining the extent of electronic coupling between molecular orbitals and semiconductor band structure. This Perspective provides an analysis and compendium of "translations" between the physics and chemistry language of group theory. In this vein, this approach describes the symmetries─and corresponding point groups─that occur in k space along the available descent in symmetry pathways (k space vectors). As a result, chemists may arrive at a more intuitive understanding of the band symmetries of semiconductors, as well as insights into the corresponding algebraic formulations. This analysis can ultimately generate MO diagrams for hybrid molecule|material systems. Lastly, an Outlook provides some context to the application of this analysis to modern problems at the interface of molecular and materials chemistry.

15.
Mol Oncol ; 18(6): 1486-1509, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38375974

RESUMO

Inter-alpha-trypsin inhibitor heavy chain 5 (ITIH5) has been identified as a metastasis suppressor gene in pancreatic cancer. Here, we analyzed ITIH5 promoter methylation and protein expression in The Cancer Genome Atlas (TCGA) dataset and three tissue microarray cohorts (n = 618), respectively. Cellular effects, including cell migration, focal adhesion formation and protein tyrosine kinase activity, induced by forced ITIH5 expression in pancreatic cancer cell lines were studied in stable transfectants. ITIH5 promoter hypermethylation was associated with unfavorable prognosis, while immunohistochemistry demonstrated loss of ITIH5 in the metastatic setting and worsened overall survival. Gain-of-function models showed a significant reduction in migration capacity, but no alteration in proliferation. Focal adhesions in cells re-expressing ITIH5 exhibited a smaller and more rounded phenotype, typical for slow-moving cells. An impressive increase of acetylated alpha-tubulin was observed in ITIH5-positive cells, indicating more stable microtubules. In addition, we found significantly decreased activities of kinases related to focal adhesion. Our results indicate that loss of ITIH5 in pancreatic cancer profoundly affects its molecular profile: ITIH5 potentially interferes with a variety of oncogenic signaling pathways, including the PI3K/AKT pathway. This may lead to altered cell migration and focal adhesion formation. These cellular alterations may contribute to the metastasis-inhibiting properties of ITIH5 in pancreatic cancer.


Assuntos
Adesão Celular , Movimento Celular , Neoplasias Pancreáticas , Transdução de Sinais , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Movimento Celular/genética , Adesão Celular/genética , Linhagem Celular Tumoral , Proteínas Tirosina Quinases/metabolismo , Proteínas Tirosina Quinases/genética , Adesões Focais/metabolismo , Adesões Focais/genética , Metilação de DNA/genética , Regiões Promotoras Genéticas/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Secretadas Inibidoras de Proteinases
16.
Ann Surg ; 279(6): 1008-1017, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38375665

RESUMO

OBJECTIVE: To examine health-related quality of life (HRQL) and satisfaction with appearance in patients who have undergone bariatric surgery (BS) with or without subsequent body contouring surgery (BCS) in relation to the general population normative for the BODY-Q. BACKGROUND: The long-term impact of BS with or without BCS has not been established using rigorously developed and validated patient-reported outcome measures. The BODY-Q is a patient-reported outcome measure developed to measure changes in HRQL and satisfaction with appearance in patients with BS and BCS. METHODS: Prospective BODY-Q data were collected from 6 European countries (Denmark, the Netherlands, Finland, Germany, Italy, and Poland) from June 2015 to February 2022 in a cohort of patients who underwent BS. Mixed-effects regression models were used to analyze changes in HRQL and appearance over time between patients who did and did not receive BCS and to examine the impact of patient-level covariates on outcomes. RESULTS: This study included 24,604 assessments from 5620 patients. BS initially led to improved HRQL and appearance scores throughout the first postbariatric year, followed by a gradual decrease. Patients who underwent subsequent BCS after BS experienced a sustained improvement in HRQL and appearance or remained relatively stable for up to 10 years postoperatively. CONCLUSIONS: Patients who underwent BCS maintained an improvement in HRQL and satisfaction with appearance in contrast to patients who only underwent BS, who reported a decline in scores 1 to 2 years postoperatively. Our results emphasize the pivotal role that BCS plays in the completion of the weight loss trajectory.


Assuntos
Cirurgia Bariátrica , Contorno Corporal , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Qualidade de Vida , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Longitudinais , Europa (Continente) , Obesidade Mórbida/cirurgia , Obesidade Mórbida/psicologia
17.
J Genet ; 1032024.
Artigo em Inglês | MEDLINE | ID: mdl-38258319

RESUMO

Dissecting the molecular basis of adaptation remains elusive despite our ability to sequence genomes and transcriptomes. At present, most genomic research on selection focusses on signatures of selective sweeps in patterns of heterozygosity. Other research has studied changes in patterns of gene expression in evolving populations but has not usually identified the genetic changes causing these shifts in expression. Here we attempt to go beyond these approaches by using machine learning tools to explore interactions between the genome, transcriptome, and life-history phenotypes in two groups of 10 experimentally evolved Drosophila populations subjected to selection for opposing life history patterns. Our findings indicate that genomic and transcriptomic data have comparable power for predicting phenotypic characters. Looking at the relationships between the genome and the transcriptome, we find that the expression of individual transcripts is influenced by many sites across the genome that are differentiated between the two types of populations. We find that single-nucleotide polymorphisms (SNPs), transposable elements, and indels are powerful predictors of gene expression. Collectively, our results suggest that the genomic architecture of adaptation is highly polygenic with extensive pleiotropy.


Assuntos
Drosophila , Genômica , Animais , Drosophila/genética , Perfilação da Expressão Gênica , Heterozigoto , Mutação INDEL
18.
Langmuir ; 40(5): 2519-2530, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38284168

RESUMO

Singlet fission produces a pair of low-energy spin-triplet excitons from a single high-energy spin-singlet exciton. While this process offers the potential to enhance the efficiency of silicon solar cells by ∼30%, meeting this goal requires overlayer materials that can efficiently transport triplet excitons to an underlying silicon substrate. Herein, we demonstrate that the chemical functionalization of silicon surfaces controls the structure of vapor-deposited thin films of perylenediimide (PDI) dyes, which are prototypical singlet fission materials. Using a combination of atomic force microscopy (AFM) and grazing-incidence wide-angle X-ray scattering (GIWAXS), we find terminating Si(111) with either a thin, polar oxide layer (SiOx) or with hydrophobic methyl groups (Si-CH3) alters the structures of the resulting PDI films. While PDI films grown on SiOx are comprised of small crystalline grains that largely adopt an "edge-on" orientation with respect to the silicon surface, films grown on Si-CH3 contain large grains that prefer to align in a "face-on" manner with respect to the substrate. This "face-on" orientation is expected to enhance exciton transport to silicon. Interestingly, we find that the preferred mode of growth for different PDIs correlates with the space group associated with bulk crystals of these compounds. While PDIs that inhabit a monoclinic (P21/c) space group nucleate films by forming tall and sparse crystalline columns, PDIs that inhabit triclinic (P1̅) space groups afford films comprised of uniform, lamellar PDI domains. The results highlight that silicon surface functionalization profoundly impacts PDI thin film growth, and rational selection of a hydrophobic surface that promotes "face-on" adsorption may improve energy transfer to silicon.

19.
Scand J Psychol ; 65(4): 569-580, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38282567

RESUMO

Transhumanism is a movement that emphasizes the improvement of the human condition by developing technologies and making them widely available. Conspiracy theories regularly refer to the allegedly transhumanist agenda of elites. We hypothesized that belief in conspiracy theories would be related to more unfavorable attitudes toward the transhumanist movement. We examined this association through two pre-registered studies (based on two French samples, total N after exclusion = 550). We found no evidence of a negative relationship between belief in conspiracy theories and attitudes toward transhumanism. This null result was further corroborated by Bayesian analysis, an equivalence test, and an internal mini meta-analysis. This work plays a precursory role in understanding attitudes toward an international cultural and intellectual movement that continues to grow in popularity and influence.


Assuntos
Atitude , Humanos , Adulto , Feminino , Masculino , Adulto Jovem , Pessoa de Meia-Idade , Humanismo
20.
FASEB J ; 38(1): e23352, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38095340

RESUMO

Inter-α-trypsin inhibitor heavy chain 5 (ITIH5) is widely expressed in the human body, and it is detected to be particularly abundant in adipose tissue. ITIH5 expression is increased in people with obesity compared to lean persons and is decreased by diet-induced weight loss. This suggests that ITIH5 may be involved in the development of adiposity and clinical metabolic variables, although its exact function remains unknown. We measured the protein concentration of ITIH5 in adipose samples from patients undergoing abdominoplasty and tested for correlation with the subjects' BMI as well as inflammatory mediators. We stimulated human adipose stem cells (ASCs) with recombinant (r)ITIH5 protein and tested for an effect on proliferation, differentiation, and immunosuppressive properties when the cells were exposed to an artificial inflammatory environment. We found positive correlations between ITIH5 levels and the BMI (p < .001) as well as concentrations of inflammatory cytokines (TNF-α, IL-6, and MCP-1) in adipose tissue (p < .01). Application of the rITIH5 protein inhibited both proliferation (p < .001) and differentiation of ASCs. Especially, the development of mature adipocytes was reduced by over 50%. Moreover, rITIH5 decreased the release of IL-6 and MCP-1 when the cells were exposed to TNF-α and IL-1ß (p < .001). Our data suggest that ITIH5 is an adipokine that is increasingly released during human adipose tissue development, acting as a regulator that inhibits proliferation and adipogenic differentiation of ASCs. ITIH5 thus presents itself as a positive regulator of adipose tissue homeostasis, possibly protecting against both hyperplasia and hypertrophy of adipose tissue and the associated chronic inflammation.


Assuntos
Citocinas , Fator de Necrose Tumoral alfa , Humanos , Citocinas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Adipócitos/metabolismo , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Adipogenia , Fatores Imunológicos/farmacologia , Células-Tronco/metabolismo , Proliferação de Células , Proteínas Secretadas Inibidoras de Proteinases/metabolismo , Proteínas Secretadas Inibidoras de Proteinases/farmacologia
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