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1.
Cereb Cortex ; 34(3)2024 03 01.
Article in English | MEDLINE | ID: mdl-38436466

ABSTRACT

The debate on whether computer gaming enhances players' cognitive function is an ongoing and contentious issue. Aiming to delve into the potential impacts of computer gaming on the players' cognitive function, we embarked on a brain imaging-derived phenotypes (IDPs)-wide Mendelian randomization (MR) study, utilizing publicly available data from a European population. Our findings indicate that computer gaming has a positive impact on fluid intelligence (odds ratio [OR] = 6.264, P = 4.361 × 10-10, 95% confidence interval [CI] 3.520-11.147) and cognitive function (OR = 3.322, P = 0.002, 95% CI 1.563-7.062). Out of the 3062 brain IDPs analyzed, only one phenotype, IDP NET100 0378, was significantly influenced by computer gaming (OR = 4.697, P = 1.10 × 10-5, 95% CI 2.357-9.361). Further MR analysis suggested that alterations in the IDP NET100 0378 caused by computer gaming may be a potential factor affecting fluid intelligence (OR = 1.076, P = 0.041, 95% CI 1.003-1.153). Our MR study lends support to the notion that computer gaming can facilitate the development of players' fluid intelligence by enhancing the connectivity between the motor cortex in the resting-state brain and key regions such as the left dorsolateral prefrontal cortex and the language center.


Subject(s)
Mendelian Randomization Analysis , Video Games , Brain/diagnostic imaging , Cognition , Computers , Intelligence , Phenotype , Neuroimaging
2.
Mar Drugs ; 22(8)2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39195464

ABSTRACT

Nonribosomal peptides (NRPs) are biosynthesized by nonribosomal peptide synthetases (NRPSs) and are widely distributed in both terrestrial and marine organisms. Many NRPs and their analogs are biologically active and serve as therapeutic agents. The adenylation (A) domain is a key catalytic domain that primarily controls the sequence of a product during the assembling of NRPs and thus plays a predominant role in the structural diversity of NRPs. Engineering of the A domain to alter substrate specificity is a potential strategy for obtaining novel NRPs for pharmaceutical studies. On the basis of introducing the catalytic mechanism and multiple functions of the A domains, this article systematically describes several representative NRPS engineering strategies targeting the A domain, including mutagenesis of substrate-specificity codes, substitution of condensation-adenylation bidomains, the entire A domain or its subdomains, domain insertion, and whole-module rearrangements.


Subject(s)
Peptide Synthases , Protein Engineering , Peptide Synthases/genetics , Peptide Synthases/metabolism , Peptide Synthases/chemistry , Substrate Specificity , Aquatic Organisms , Catalytic Domain , Animals
3.
Nano Lett ; 23(11): 5123-5130, 2023 Jun 14.
Article in English | MEDLINE | ID: mdl-37272668

ABSTRACT

Developing cost-effective and highly efficient photocathodes toward polysulfide redox reduction is highly desirable for advanced quantum dot (QD) photovoltaics. Herein, we demonstrate nitrogen doped carbon (N-C) shell-supported iron single atom catalysts (Fe-SACs) capable of catalyzing polysulfide reduction in QD photovoltaics for the first time. Specifically, Fe-SACs with FeN4 active sites feature a power conversion efficiency of 13.7% for ZnCuInSe-QD photovoltaics (AM1.5G, 100 mW/cm2), which is the highest value for ZnCuInSe QD-based photovoltaics, outperforming those of Cu-SACs and N-C catalysts. Compared with N-C, Fe-SACs exhibit suitable energy level matching with polysulfide redox couples, revealed by the Kelvin probe force microscope, which accelerates the charge transferring at the interfaces of catalyst/polysulfide redox couple. Density functional theory calculations demonstrate that the outstanding catalytic activity of Fe-SACs originates from the preferable adsorption of S42- on the FeN4 active sites and the high activation degree of the S-S bonds in S42- initiated by the FeN4 active sites.

4.
PLoS Pathog ; 17(3): e1009481, 2021 03.
Article in English | MEDLINE | ID: mdl-33788895

ABSTRACT

TcpC is a virulence factor of uropathogenic E. coli (UPEC). It was found that TIR domain of TcpC impedes TLR signaling by direct association with MyD88. It has been a long-standing question whether bacterial pathogens have evolved a mechanism to manipulate MyD88 degradation by ubiquitin-proteasome pathway. Here, we show that TcpC is a MyD88-targeted E3 ubiquitin ligase. Kidney macrophages from mice with pyelonephritis induced by TcpC-secreting UPEC showed significantly decreased MyD88 protein levels. Recombinant TcpC (rTcpC) dose-dependently inhibited protein but not mRNA levels of MyD88 in macrophages. Moreover, rTcpC significantly promoted MyD88 ubiquitination and accumulation in proteasomes in macrophages. Cys12 and Trp106 in TcpC are crucial amino acids in maintaining its E3 activity. Therefore, TcpC blocks TLR signaling pathway by degradation of MyD88 through ubiquitin-proteasome system. Our findings provide not only a novel biochemical mechanism underlying TcpC-medicated immune evasion, but also the first example that bacterial pathogens inhibit MyD88-mediated signaling pathway by virulence factors that function as E3 ubiquitin ligase.


Subject(s)
Escherichia coli Proteins/metabolism , Myeloid Differentiation Factor 88/metabolism , Signal Transduction/physiology , Uropathogenic Escherichia coli/pathogenicity , Virulence Factors/metabolism , Animals , Cell Line , Female , Humans , Immune Evasion/physiology , Macrophages , Mice , Mice, Inbred C57BL , Pyelonephritis/immunology , Pyelonephritis/microbiology , Toll-Like Receptors/metabolism , Ubiquitin-Protein Ligases/metabolism , Uropathogenic Escherichia coli/immunology , Uropathogenic Escherichia coli/metabolism , Virulence/physiology
5.
Mar Drugs ; 21(4)2023 Mar 29.
Article in English | MEDLINE | ID: mdl-37103356

ABSTRACT

Aeruginosins, a family of nonribosomal linear tetrapeptides discovered from cyanobacteria and sponges, exhibit in vitro inhibitory activity on various types of serine proteases. This family is characterized by the existence of the 2-carboxy-6-hydroxy-octahydroindole (Choi) moiety occupied at the central position of the tetrapeptide. Aeruginosins have attracted much attention due to their special structures and unique bioactivities. Although many studies on aeruginosins have been published, there has not yet been a comprehensive review that summarizes the diverse research ranging from biogenesis, structural characterization and biosynthesis to bioactivity. In this review, we provide an overview of the source, chemical structure as well as spectrum of bioactivities of aeruginosins. Furthermore, possible opportunities for future research and development of aeruginosins were discussed.


Subject(s)
Biological Products , Cyanobacteria , Peptides , Peptides/chemistry , Biological Products/chemistry
6.
Parasitol Res ; 122(7): 1567-1572, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37212833

ABSTRACT

Mites serve as pathogens, allergens, or microbial containers, which can seriously damage the health of humans and animals. The substantial amount of mite species and their similar morphology make it complicated to identify and classify. Our mouse breeder incidentally noticed papular-type erythema with itching and peeling of the skin in several places, and an investigation revealed that this symptom was caused by an uncommon parasite that appeared on the skin and around the nest of the mice. By morphological observation, DNA extraction, PCR amplification, and DNA sequencing, we roughly identified the category of the parasite as a mite. Then, we designed a specific primer cox1, amplified and sequenced the mitochondrial cox1 gene fragment of the mite, calculated the intraspecific and interspecific differences, and reconstructed the phylogenetic tree for sequence alignment. Finally, this species was identified and named this Ornithonyssus bacoti-KF. According to the ivermectin gradient test, we found that 0.1 mg/mL concentration of ivermectin solution was the most effective for mite removal in the bath, with no recurrence after 6 months of treatment. Ornithonyssus bacoti, diagnosed by microscopic exam and confirmed by PCR amplification sequencing, was treated with ivermectin to control the rodent-borne parasite effectively.


Subject(s)
Mite Infestations , Mites , Humans , Animals , Mice , Mite Infestations/diagnosis , Mite Infestations/drug therapy , Mite Infestations/parasitology , Ivermectin , Phylogeny , Skin
7.
Int J Mol Sci ; 24(5)2023 Feb 22.
Article in English | MEDLINE | ID: mdl-36901796

ABSTRACT

The water-to-land transition is one of the most important events in evolutionary history of vertebrates. However, the genetic basis underlying many of the adaptations during this transition remains unclear. Mud-dwelling gobies in the subfamily Amblyopinae are one of the teleosts lineages that show terrestriality and provide a useful system for clarifying the genetic changes underlying adaptations to terrestrial life. Here, we sequenced the mitogenome of six species in the subfamily Amblyopinae. Our results revealed a paraphyletic origin of Amblyopinae with respect to Oxudercinae, which are the most terrestrial fishes and lead an amphibious life in mudflats. This partly explains the terrestriality of Amblyopinae. We also detected unique tandemly repeated sequences in the mitochondrial control region in Amblyopinae, as well as in Oxudercinae, which mitigate oxidative DNA damage stemming from terrestrial environmental stress. Several genes, such as ND2, ND4, ND6 and COIII, have experienced positive selection, suggesting their important roles in enhancing the efficiency of ATP production to cope with the increased energy requirements for life in terrestrial environments. These results strongly suggest that the adaptive evolution of mitochondrial genes has played a key role in terrestrial adaptions in Amblyopinae, as well as in Oxudercinae, and provide new insights into the molecular mechanisms underlying the water-to-land transition in vertebrates.


Subject(s)
Genome, Mitochondrial , Perciformes , Animals , Perciformes/genetics , Adaptation, Physiological , Ecosystem , Water , Phylogeny
8.
Socioecon Plann Sci ; 85: 101430, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36093279

ABSTRACT

After the outbreak of COVID-19, the freight demand fell briefly, and as production resumed, the trucking share rate increased again, further increasing energy consumption and environmental pollution. To optimize the sudden changing freight structure, the study aims on developing an evolution model based on Markov's theory to estimate the freight structure post-COVID-19. The current study applies economic cybernetics to establish a freight structural adjustment path optimization model and solve the problem of how much freight transportation should increase each year under the premise that the total turnover of the freight industry continues to grow, and how many years it will take at least to reach a reasonable freight structure. The freight transport structure of China is used to examine the feasibility of the proposed model. The finding indicates that the development of China's freight transport structure is at an adjustment period and should enter a stable period by 2035 and the COVID-19 makes it harder to adjust the freight structure. Increasing the growth rate of the freight volume of railway and waterway transportation is the key to realizing the optimization of the freight structure, and the freight structure path optimization method can realize the rationalization of the freight structure in advance.

9.
Sensors (Basel) ; 22(20)2022 Oct 21.
Article in English | MEDLINE | ID: mdl-36298387

ABSTRACT

Mental fatigue is a widely studied topic on account of its serious negative effects. But how the neural mechanism of task switching before and after mental fatigue remains a question. To this end, this study aims to use brain functional network features to explore the answer to this question. Specifically, task-state EEG signals were recorded from 20 participants. The tasks include a 400-s 2-back-task (2-BT), followed by a 6480-s of mental arithmetic task (MAT), and then a 400-s 2-BT. Network features and functional connections were extracted and analyzed based on the selected task switching states, referred to from Pre_2-BT to Pre_MAT before mental fatigue and from Post_MAT to Post_2-BT after mental fatigue. The results showed that mental fatigue has been successfully induced by long-term MAT based on the significant changes in network characteristics and the high classification accuracy of 98% obtained with Support Vector Machines (SVM) between Pre_2-BT and Post_2-BT. when the task switched from Pre_2-BT to Pre_MAT, delta and beta rhythms exhibited significant changes among all network features and the selected functional connections showed an enhanced trend. As for the task switched from Post_MAT to Post_2-BT, the network features and selected functional connectivity of beta rhythm were opposite to the trend of task switching before mental fatigue. Our findings provide new insights to understand the neural mechanism of the brain in the process of task switching and indicate that the network features and functional connections of beta rhythm can be used as neural markers for task switching before and after mental fatigue.


Subject(s)
Electroencephalography , Mental Fatigue , Humans , Electroencephalography/methods , Brain , Brain Mapping , Support Vector Machine
10.
Sensors (Basel) ; 22(14)2022 Jul 20.
Article in English | MEDLINE | ID: mdl-35891100

ABSTRACT

Although increasing evidences support the notion that psychiatric disorders are associated with abnormal communication between brain regions, scattered studies have investigated brain electrophysiological disconnectivity of patients with generalized anxiety disorder (GAD). To this end, this study intends to develop an analysis framework for automatic GAD detection through incorporating multidimensional EEG feature extraction and machine learning techniques. Specifically, resting-state EEG signals with a duration of 10 min were obtained from 45 patients with GAD and 36 healthy controls (HC). Then, an analysis framework of multidimensional EEG characteristics (including univariate power spectral density (PSD) and fuzzy entropy (FE), and multivariate functional connectivity (FC), which can decode the EEG information from three different dimensions) were introduced for extracting aberrated multidimensional EEG features via statistical inter-group comparisons. These aberrated features were subsequently fused and fed into three previously validated machine learning methods to evaluate classification performance for automatic patient detection. We showed that patients exhibited a significant increase in beta rhythm and decrease in alpha1 rhythm of PSD, together with the reduced long-range FC between frontal and other brain areas in all frequency bands. Moreover, these aberrated features contributed to a very good classification performance with 97.83 ± 0.40% of accuracy, 97.55 ± 0.31% of sensitivity, 97.78 ± 0.36% of specificity, and 97.95 ± 0.17% of F1. These findings corroborate previous hypothesis of disconnectivity in psychiatric disorders and further shed light on distribution patterns of aberrant spatio-spectral EEG characteristics, which may lead to potential application of automatic diagnosis of GAD.


Subject(s)
Electroencephalography , Machine Learning , Anxiety Disorders/diagnosis , Brain , Electroencephalography/methods , Entropy , Humans
11.
Entropy (Basel) ; 24(3)2022 Mar 19.
Article in English | MEDLINE | ID: mdl-35327935

ABSTRACT

Offline hand-drawn diagram recognition is concerned with digitizing diagrams sketched on paper or whiteboard to enable further editing. Some existing models can identify the individual objects like arrows and symbols, but they become involved in the dilemma of being unable to understand a diagram's structure. Such a shortage may be inconvenient to digitalization or reconstruction of a diagram from its hand-drawn version. Other methods can accomplish this goal, but they live on stroke temporary information and time-consuming post-processing, which somehow hinders the practicability of these methods. Recently, Convolutional Neural Networks (CNN) have been proved that they perform the state-of-the-art across many visual tasks. In this paper, we propose DrawnNet, a unified CNN-based keypoint-based detector, for recognizing individual symbols and understanding the structure of offline hand-drawn diagrams. DrawnNet is designed upon CornerNet with extensions of two novel keypoint pooling modules which serve to extract and aggregate geometric characteristics existing in polygonal contours such as rectangle, square, and diamond within hand-drawn diagrams, and an arrow orientation prediction branch which aims to predict which direction an arrow points to through predicting arrow keypoints. We conducted wide experiments on public diagram benchmarks to evaluate our proposed method. Results show that DrawnNet achieves 2.4%, 2.3%, and 1.7% recognition rate improvements compared with the state-of-the-art methods across benchmarks of FC-A, FC-B, and FA, respectively, outperforming existing diagram recognition systems on each metric. Ablation study reveals that our proposed method can effectively enable hand-drawn diagram recognition.

12.
J Infect Dis ; 224(4): 620-631, 2021 08 16.
Article in English | MEDLINE | ID: mdl-33864371

ABSTRACT

BACKGROUND: We investigatedthe association between time-averaged area under the curve (AAUC) of cytomegalovirus (CMV) viral load (VL) by day 100 and overall survival (OS) at 1-year after hematopoietic cell transplantation (HCT). METHODS: In a retrospective cohort study, including patients receiving HCT between June 2010 and December 2017 from Memorial Sloan Kettering Cancer Center, AAUC was calculated for patients with detected VL. Patients were categorized into non-controllers (Q4) and controllers (Q1-Q3) using the highest AAUC quartile as cutoff. Cox models were used to estimate the association between AAUC and OS. Patients with non-detected CMV VL were categorized into elite-controllers (recipient+ [R+] or R-/donor+ [D+]) and R-/D-. RESULTS: The study (N = 952) included 282 controllers, 93 non-controllers, 275 elite-controllers, and 302 R-/D-. OS was 80.1% and 58.1% for controllers and non-controllers, respectively. In multivariable models, non-controllers had worse OS versus controllers (adjusted hazard ratio [HR] = 2.65; 95% confidence interval [CI], 1.71-4.12). In landmark analyses, controllers had similar OS as elite-controllers (HR = 1.26; 95% CI, .83-1.91) or R-/D- (HR = 0.98; 95% CI, .64-1.5). CONCLUSIONS: Non-controllers had worse OS 1-year post-HCT. Controllers had similar OS as elite-controllers or R-/D-. Future studies are needed to validate our AAUC cutoff across different cohorts and CMV management strategies.


Subject(s)
Cytomegalovirus Infections , Hematopoietic Stem Cell Transplantation , Multiple Organ Failure/mortality , Viral Load , Cytomegalovirus , Cytomegalovirus Infections/mortality , Humans , Kinetics , Multiple Organ Failure/virology , Retrospective Studies , Survival Rate
13.
J Infect Dis ; 222(7): 1180-1187, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32374872

ABSTRACT

BACKGROUND: We report on predictors of adenovirus (ADV) viremia and correlation of ADV viral kinetics with mortality in ex vivo T-cell depleted (TCD) hematopoietic cell transplant (HCT). METHODS: T cell-depleted HCT recipients from January 1, 2012 through September 30, 2018 were prospectively monitored for ADV in the plasma through Day (D) +100 posttransplant or for 16 weeks after the onset of ADV viremia. Adenovirus viremia was defined as ≥2 consecutive viral loads (VLs) ≥1000 copies/mL through D +100. Time-averaged area under the curve (AAUC) or peak ADV VL through 16 weeks after onset of ADV viremia were explored as predictors of mortality in Cox models. RESULTS: Of 586 patients (adult 81.7%), 51 (8.7%) developed ADV viremia by D +100. Age <18 years, recipient cytomegalovirus seropositivity, absolute lymphocyte count <300 cells/µL at D +30, and acute graft-versus-host disease were predictors of ADV viremia in multivariate models. Fifteen (29%) patients with ADV viremia died by D +180; 8 of 15 (53%) died from ADV. Peak ADV VL (hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.52-3.33) and increasing AAUC (HR, 2.95; 95% CI, 1.83-4.75) correlated with mortality at D +180. CONCLUSIONS: In TCD HCT, peak ADV VL and ADV AAUC correlated with mortality at D +180. Our data support the potential utility of ADV viral kinetics as endpoints in clinical trials of ADV therapies.


Subject(s)
Adenoviridae Infections/mortality , Hematopoietic Stem Cell Transplantation , Lymphocyte Depletion , T-Lymphocytes/immunology , Transplantation Conditioning , Viremia/mortality , Adenoviridae/growth & development , Adenoviridae Infections/immunology , Adolescent , Adult , Child , Child, Preschool , Female , Graft vs Host Disease/immunology , Graft vs Host Disease/mortality , Graft vs Host Disease/virology , Hematologic Diseases/immunology , Hematologic Diseases/mortality , Hematologic Diseases/virology , Humans , Kinetics , Male , Middle Aged , Myeloablative Agonists/therapeutic use , Survival Analysis , T-Lymphocytes/transplantation , Transplantation, Homologous , Viral Load , Viremia/immunology
14.
Biol Blood Marrow Transplant ; 26(10): 1937-1947, 2020 10.
Article in English | MEDLINE | ID: mdl-32640313

ABSTRACT

Cytomegalovirus (CMV) viremia occurs in 40% to 80% of CMV-seropositive (R+) recipients of allogeneic hematopoietic cell transplantation (HCT). The preemptive therapy (PET) strategy has reduced the risk of CMV end-organ disease (EOD) and associated mortality but may lead to substantial healthcare resource utilization (HCRU) and costs. Real-world data on the economic impact of PET is relevant for the evaluation of alternative strategies for CMV management. We examined the impact of clinically significant CMV treated with PET on inpatient length of stay (LOS), number of readmissions, and associated costs from day 0 through day 180 post-HCT. This was a retrospective study of R+ adults who underwent peripheral blood or marrow allogeneic HCT at Memorial Sloan Kettering Cancer Center between March 2013 and December 2017. Patients were routinely screened for CMV by qPCR and received PET according to institutional standards of care. Data were extracted from electronic medical records and hospital databases. Itemized cost data per patient were obtained from the Vizient database, adjusted to 2017 dollars using inflation indices. Study outcomes included HCRU evaluated by inpatient LOS and inpatient cost in patients who received PET for clinically significant CMV (PET group) compared with those who did not receive PET (no PET group) and the frequency and cost of CMV-related readmissions compared with non CMV-related readmissions. We used generalized linear models to examine the incremental HCRU and costs associated with PET controlling for other potential factors. Of 357 patients, PET was initiated in 208 (58.3%), at a median of 35 days after HCT. By day 180, 23 patients (6.4%) had developed CMV EOD and 3 (.8%) had died of CMV. Compared with the no PET group, the PET group had a longer LOS for HCT admission (P = .0276), longer total LOS by day 180 (P = .0001), a higher number of readmissions (P = .0001), a higher mean inpatient cost for HCT admission ($189,389 versus $151,646; P = .0133), and a higher total inpatient cost ($297,563 versus $205,815; P < .0001). Among PET recipients, CMV-related readmissions were associated with higher mean cost per episode compared with non CMV-related readmissions ($165,455 versus $89,419; P = .005). CMV-related readmissions comprised 40.6% of total all-cause readmissions and incurred 55.9% of total all-cause readmission costs in PET recipients. Our data show that patients treated with currently available PET had greater inpatient HCRU and cost, by day 180 compared with patients who did not receive PET. The cost of CMV-related readmissions accounted for 56% of total readmission cost among PET recipients. Future studies are needed to examine the cost-effectiveness of alternative strategies for CMV management.


Subject(s)
Cytomegalovirus Infections , Hematopoietic Stem Cell Transplantation , Adult , Antiviral Agents/therapeutic use , Cytomegalovirus , Cytomegalovirus Infections/drug therapy , Hospitalization , Humans , Retrospective Studies
15.
Biol Blood Marrow Transplant ; 26(8): 1482-1491, 2020 08.
Article in English | MEDLINE | ID: mdl-32315708

ABSTRACT

(Val)ganciclovir (vGCV) or foscarnet (FCN) as preemptive therapy (PET) for cytomegalovirus (CMV) after allogeneic hematopoietic cell transplantation (HCT) is associated with myelosuppression and nephrotoxicity, respectively. We analyzed a cohort of CMV-seropositive (R+) HCT recipients managed preemptively at a single center. The objectives of our study were to (1) quantify the frequencies of neutropenia and acute kidney injury (AKI) through day +100 (D100) post-HCT and at PET discontinuation and (2) assess the impact of PET on neutropenia and AKI in multivariate models. This was a retrospective cohort study of adult CMV R+ recipients who underwent allo-HCT at Memorial Sloan Kettering Cancer Center from March 18, 2013, through December 31, 2017, and were managed with PET. Patients were grouped by receipt of PET (PET and no PET). Neutropenia and AKI were defined by Common Terminology Criteria for Adverse Events version 4. Frequencies of toxicities by D100 were compared between relevant groups. The impact of PET on toxicities was examined in univariate and multivariate Poisson/negative binomial regression models. Of 368 CMV R+ HCT recipients, 208 (56.5%) received PET. Neutropenia by D100 occurred in 41.8% and 28.6% patients in PET and no PET, respectively (P = .0009). PET increased the risk of neutropenia (adjusted relative risk = 1.81; 95% confidence interval [CI], 1.48 to 2.21; P < .0001) in multivariate analyses. AKI by D100 occurred in 12.0% and 7.8% patients in PET and no PET, respectively (P = .19). PET increased the risk of AKI by 2.75-fold (95% CI, 1.71 to 4.42; P < .0001). When PET recipients were grouped by first antiviral, neutropenia by D100 occurred in 34.8% and 48.9% of vGCV and FCN recipients, respectively, (P = .08), and AKI occurred in 13.0% and 34.0% of vGCV and FCN recipients, respectively (P = .001). At discontinuation of vGCV or FCN, neutropenia was present in 11.2% versus 2.1% patients, respectively (P = .08), and AKI was present in 1.9% of versus 12.8% patients respectively (P = .005). Preemptive therapy for CMV increased the risk of neutropenia and AKI in the first 100 days post-HCT by 1.8-fold and 2.8-fold, respectively. Our results underscore the need for safer antivirals for CMV management in HCT recipients.


Subject(s)
Cytomegalovirus Infections , Hematopoietic Stem Cell Transplantation , Adult , Antiviral Agents/adverse effects , Cohort Studies , Cytomegalovirus , Cytomegalovirus Infections/drug therapy , Ganciclovir/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Retrospective Studies
16.
Org Biomol Chem ; 16(16): 3026-3037, 2018 04 25.
Article in English | MEDLINE | ID: mdl-29634066

ABSTRACT

A biomimetic synthetic strategy and combinatorial chemistry were used to synthesize 34 novel monoterpenoid indole alkaloid (MIA) analogues, and their cytotoxic activities against five cancer cell lines (SW-480, A-549, HL-60, SMMC-7721, and MCF-7) were determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Fourteen of these analogues (7, 16-18, and 23-32) showed significantly greater inhibition of tumour cell proliferation than cisplatin. Compounds 17 and 18 showed the highest cytotoxic activity against the HL-60 cell line with IC50 values of 0.90 µM and 0.43 µM, respectively. Compound 18 slightly induced apoptosis and arrested the cell cycle in SW-480, A-549, HL-60, SMMC-7721, and MCF-7 cells. Analysis of the primary structure-activity relationships reveals that the introduction of different substituent groups at the C-3, C-5, and C-6 positions of the indole moiety and the C-10 position of the genipin moiety might have an effect on the antitumour activity of the resulting compounds.


Subject(s)
Antineoplastic Agents , Secologanin Tryptamine Alkaloids/analogs & derivatives , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Cisplatin/pharmacology , Drug Design , Drug Screening Assays, Antitumor , Humans , Neoplasms/drug therapy , Neoplasms/pathology , Secologanin Tryptamine Alkaloids/chemical synthesis , Secologanin Tryptamine Alkaloids/pharmacology , Structure-Activity Relationship
17.
BMC Med Inform Decis Mak ; 18(1): 134, 2018 12 17.
Article in English | MEDLINE | ID: mdl-30558581

ABSTRACT

BACKGROUND: Breast cancer chemoprevention can reduce breast cancer incidence in high-risk women; however, chemoprevention is underutilized in the primary care setting. We conducted a pilot study of decision support tools among high-risk women and their primary care providers (PCPs). METHODS: The intervention included a decision aid (DA) for high-risk women, RealRisks, and a provider-centered tool, Breast Cancer Risk Navigation (BNAV). Patients completed validated surveys at baseline, after RealRisks and after their PCP clinical encounter or at 6-months. Referral for high-risk consultation and chemoprevention uptake were assessed via the electronic health record. The primary endpoint was accuracy of breast cancer risk perception at 6-months. RESULTS: Among 40 evaluable high-risk women, median age was 64.5 years and median 5-year breast cancer risk was 2.19%. After exposure to RealRisks, patients demonstrated an improvement in accurate breast cancer risk perceptions (p = 0.02), an increase in chemoprevention knowledge (p < 0.01), and 24% expressed interest in taking chemoprevention. Three women had a high-risk referral, and no one initiated chemoprevention. Decisional conflict significantly increased from after exposure to RealRisks to after their clinical encounter or at 6-months (p < 0.01). Accurate breast cancer risk perceptions improved and was sustained at 6-months or after clinical encounters. We discuss the side effect profile of chemoprevention and the care pathway when RealRisks was introduced to understand why patients experienced increased decision conflict. CONCLUSION: Future interventions should carefully link the use of a DA more proximally to the clinical encounter, investigate timed measurements of decision conflict and improve risk communication, shared decision making, and chemoprevention education for PCPs. Additional work remains to better understand the impact of decision aids targeting both patients and providers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02954900 November 4, 2016 Retrospectively registered.


Subject(s)
Breast Neoplasms/prevention & control , Chemoprevention , Clinical Decision-Making , Decision Making , Decision Support Techniques , Health Knowledge, Attitudes, Practice , Primary Health Care , Risk Assessment , Adult , Aged , Female , Humans , Middle Aged , Pilot Projects
18.
Food Chem ; 446: 138831, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38402759

ABSTRACT

Carvacrol is well-known natural antimicrobial compounds. However, its usage in fruit preservation is restricted owing to poor water solubility. Our study aims to address this limitation by combining carvacrol with whey protein isolate (WPI) to form nanoemulsion and enhancing antimicrobial properties and stability of nanoemulsion through ε-polylysine addition, thereby improving their application in fruit preservation. The results indicated that the nanoemulsion exhibited a double-layer structure. The physicochemical properties and storage stability were found to be favorable under the conditions of WPI (0.3 wt% v/v), Carvacrol (0.5 % v/v), and ε-polylysine (0.3 wt% v/v). In addition, the nanoemulsion had inhibitory effects on Staphylococcus aureus, Escherichia coli, and Aspergillus niger at concentrations of minimal inhibition concentration (32, 32, and 200 µg/mL, respectively). In addition, during a 7-day storage period, the nanoemulsion effectively preserved mangoes. Therefore, nanoemulsion could serve as a candidate for control of postharvest mangoes spoilage and extend its period of storage.


Subject(s)
Anti-Infective Agents , Cymenes , Mangifera , Polylysine/chemistry , Emulsions/pharmacology , Anti-Infective Agents/pharmacology , Escherichia coli
19.
Diagnostics (Basel) ; 14(11)2024 May 28.
Article in English | MEDLINE | ID: mdl-38893648

ABSTRACT

Current assessments for generalized anxiety disorder (GAD) are often subjective and do not rely on a standardized measure to evaluate the GAD across its severity levels. The lack of objective and multi-level quantitative diagnostic criteria poses as a significant challenge for individualized treatment strategies. To address this need, this study aims to establish a GAD grading and quantification diagnostic model by integrating an electroencephalogram (EEG) and ensemble learning. In this context, a total of 39 normal subjects and 80 GAD patients were recruited and divided into four groups: normal control, mild GAD, moderate GAD, and severe GAD. Ten minutes resting state EEG data were collected for every subject. Functional connectivity features were extracted from each EEG segment with different time windows. Then, ensemble learning was employed for GAD classification studies and brain mechanism analysis. Hence, the results showed that the Catboost model with a 10 s time window achieved an impressive 98.1% accuracy for four-level classification. Particularly, it was found that those functional connections situated between the frontal and temporal lobes were significantly more abundant than in other regions, with the beta rhythm being the most prominent. The analysis framework and findings of this study provide substantial evidence for the applications of artificial intelligence in the clinical diagnosis of GAD.

20.
Food Chem ; 460(Pt 3): 140593, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39111046

ABSTRACT

Zearalenone contaminates food and poses a threat to human health. It is vital to develop cost-effective and environmentally-friendly adsorbents for its removal. By screening Sporobolomyces pararoseus (SZ4) and modified yam starch (adsorption capacity (qe) of 1.33 and 0.94 mg/g, respectively), this study prepared a novel composite aerogel adsorbent (P-YSA@SZ410). The compressive strength of P-YSA@SZ410 was 1.35-fold higher than unloaded yeast. It contained several functional groups and three-dimensional interconnected channels, achieving a 0° contact angle within 0.18 s, thereby demonstrating excellent water-absorbent properties. With a qe of 2.96 mg/g at 308 K, the adsorption process of P-YSA@SZ410 was spontaneous, endothermic, and matched pseudo-second-order and Langmuir models. The composite adsorbed zearalenone via electrostatic attraction and hydrogen bonding, maintaining a qe of 2.24 mg/g after five cycles. P-YSA@SZ410 was found to remove zearalenone effectively under various conditions and could be applied to corn silk tea, indicating its great potential as an adsorbent material.


Subject(s)
Starch , Zea mays , Zearalenone , Zearalenone/chemistry , Starch/chemistry , Zea mays/chemistry , Adsorption , Dioscorea/chemistry , Food Contamination/analysis , Porosity , Basidiomycota/chemistry , Gels/chemistry , Kinetics
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