Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 4.798
Filter
1.
J Colloid Interface Sci ; 672: 63-74, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38830319

ABSTRACT

Multidrug-resistant (MDR) bacteria-infected wound healing remains greatly challenging, especially in diabetic patients. Herein, a novel nano-drug delivery based on endogenous glucose-driven cascade reaction is proposed for boosting MDR bacteria-infected diabetic wound healing with high efficacy by improving wound microenvironment and enhancing photodynamic antibacterial activity. The composite nanoagent is first self-assembled by integrating berberine (BBR) and epigallocatechin gallate (EGCG) from natural plant extracts, named as BENPs, which is successively coated with manganese dioxide nanoshells (MnO2 NSs) and glucose oxidase (GOX) to form the final BEMGNPs. The cascade reaction is triggered by glucose at the wound site of diabetes which is specifically catalyzed by GOX in the BEMGNPs to produce gluconic acid and hydrogen peroxide (H2O2). That is subsequently to decompose MnO2 NSs in the BEMGNPs to generate oxygen (O2). The BEMGNPs as photosensitizers effectively produce reactive oxygen species (ROS) to enhance the eradication of bacteria with the assistance of O2. Under the synergistic function of the cascaded reaction, the BEMGNPs present excellent antibacterial efficacy even for MDR bacteria. The in vivo experiments explicitly validate that the constructed nano-drug delivery can augment the MDR bacteria-infected diabetic wound healing with excellent biosafety. The as-proposed strategy provides an instructive way to combat ever-threatening MDR bacteria, which particularly is beneficial for diabetic patients.

2.
Sci Rep ; 14(1): 12621, 2024 06 01.
Article in English | MEDLINE | ID: mdl-38824201

ABSTRACT

Anaplasma and Ehrlichia are tick-borne bacterial pathogens that cause anaplasmoses and ehrlichioses in humans and animals. In this study, we examined the prevalence of Anaplasma and Ehrlichia species in ticks and domesticated animals in Suizhou County, Hubei Province in the central China. We used PCR amplification and DNA sequencing of the 16S rRNA, groEL, and gltA genes to analyze. We collected 1900 ticks, including 1981 Haemaphysalis longicornis and 9 Rhipicephalus microplus, 159 blood samples of goats (n = 152), cattle (n = 4), and dogs (n = 3) from May to August of 2023. PCR products demonstrated that Anaplasma bovis, Anaplasma capra, and an Ehrlichia species were detected in the H. longicornis with the minimum infection rates (MIR) of 1.11%, 1.32%, and 0.05%, respectively; A. bovis, A. capra, and unnamed Anaplasma sp. were detected in goats with an infection rate of 26.31%, 1.31% and 1.97%, respectively. Anaplasma and Ehrlichia species were not detected from cattle, dogs and R. microplus ticks. The genetic differences in the groEL gene sequences of the Anaplasma in the current study were large, whereas the 16S rRNA and gltA gene sequences were less disparate. This study shows that ticks and goats in Suizhou County, Hubei Province carry multiple Anaplasma species and an Ehrlichia species, with relatively higher infection rate of A. bovis in goats. Our study indicates that multiple Anaplasma and Ehrlichia species exist in ticks and goats in the central China with potential to cause human infection.


Subject(s)
Anaplasma , Anaplasmosis , Animals, Domestic , Ehrlichia , Genetic Variation , Goats , RNA, Ribosomal, 16S , Animals , Anaplasma/genetics , Anaplasma/isolation & purification , China/epidemiology , Ehrlichia/genetics , Ehrlichia/isolation & purification , Goats/microbiology , Dogs , Cattle , Anaplasmosis/epidemiology , Anaplasmosis/microbiology , Prevalence , Animals, Domestic/microbiology , RNA, Ribosomal, 16S/genetics , Ticks/microbiology , Ehrlichiosis/epidemiology , Ehrlichiosis/veterinary , Ehrlichiosis/microbiology , Phylogeny
3.
J Adolesc Health ; 2024 May 11.
Article in English | MEDLINE | ID: mdl-38739050

ABSTRACT

PURPOSE: Depression and suicidal ideation (SI) are common in adolescents. However, the relation between the two is unclear. According to the cognitive model of suicidal behavior and learned helplessness theory, lack of certainty in control (LCC), referring to individuals' deficiency in predictability, certainty, and control of life, may be an important factor linking the two. Thus, the current study aimed to investigate the temporal relation between depression and SI in adolescents and to assess the mediating role of LCC in this relation. METHODS: A three-wave survey was carried out at intervals of 1 and 1.5 years among 516 adolescents at several middle schools in Sichuan Province, China. The random-intercept cross-lagged panel model was used to examine the temporal relations between depression, SI, and LCC among adolescents, which can effectively distinguish between-person and within-person differences. RESULTS: The results revealed that depression, SI, and LCC had positive intercorrelations at the between-person level. At the within-person level, early depression predicted subsequent depression and SI via LCC among adolescents. Additionally, early LCC promoted later SI through depression. DISCUSSION: These findings highlight the mediating role of LCC, clarify the temporal relation between depression and SI, and provide theoretical support for interventions to address depression and suicide.

4.
IEEE Trans Biomed Eng ; PP2024 May 20.
Article in English | MEDLINE | ID: mdl-38768001

ABSTRACT

Freezing of gait (FOG) leads to an increased risk of falls and limited mobility in individuals with Parkinson's disease (PD). However, existing research ignores the fine-grained quantitative assessment of FOG severity. This paper provides a double-hurdle model that uses typical spatiotemporal gait features to quantify the FOG severity in patients with PD. Moreover, a novel multi-output random forest algorithm is used as one hurdle of the double-hurdle model, further enhancing the model's performance. We conduct six experiments on a public PD gait database. Results demonstrate that the designed random forest algorithm in the double-hurdle model-hyperparameter independence framework achieves outstanding performances with the highest correlation coefficient (CC) of 0.972 and the lowest root mean square error (RMSE) of 2.488. Furthermore, we study the effect of drug state on the gait patterns of PD patients with or without FOG. Results show that "OFF" state amplifies the visibility of FOG symptoms in PD patients. Therefore, this study holds significant implications for the management and treatment of PD.

5.
Cells ; 13(9)2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38727267

ABSTRACT

The unique prolyl isomerase Pin1 binds to and catalyzes cis-trans conformational changes of specific Ser/Thr-Pro motifs after phosphorylation, thereby playing a pivotal role in regulating the structure and function of its protein substrates. In particular, Pin1 activity regulates the affinity of a substrate for E3 ubiquitin ligases, thereby modulating the turnover of a subset of proteins and coordinating their activities after phosphorylation in both physiological and disease states. In this review, we highlight recent advancements in Pin1-regulated ubiquitination in the context of cancer and neurodegenerative disease. Specifically, Pin1 promotes cancer progression by increasing the stabilities of numerous oncoproteins and decreasing the stabilities of many tumor suppressors. Meanwhile, Pin1 plays a critical role in different neurodegenerative disorders via the regulation of protein turnover. Finally, we propose a novel therapeutic approach wherein the ubiquitin-proteasome system can be leveraged for therapy by targeting pathogenic intracellular targets for TRIM21-dependent degradation using stereospecific antibodies.


Subject(s)
NIMA-Interacting Peptidylprolyl Isomerase , Proteolysis , Ubiquitination , Humans , NIMA-Interacting Peptidylprolyl Isomerase/metabolism , Protein Conformation , Animals , Neoplasms/metabolism , Neoplasms/pathology , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Ubiquitin-Protein Ligases/metabolism
6.
Heliyon ; 10(9): e30718, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38765065

ABSTRACT

Although serum albumin and neuroticism have revealed a strong association with suicidal ideation in individuals with depression, the causal relationship between them is uncertain. This study analyzed the causal association of serum albumin, neuroticism and suicidal ideation using large-scale GWAS data and Univariable Mendelian Randomization (UVMR) methods. The Multivariable MR (MVMR) analysis was used to explore the causal pathways. UVMR analysis revealed that genetically determined serum albumin is causally associated with neuroticism (ß = -0.006 S.D.; 95 % CI: 0.009, -0.002; p = 0.003) and suicidal ideation (ß = 0.009 S.D.; 95 % CI: 0.001, 0.016; p = 0.037); and that neuroticism mediates 100 % of the causal association between serum albumin and suicidal ideation in individuals with depression. These findings suggest genetic evidence for the causal effect of serum albumin on suicidal ideation in depressed patients and the significant mediation effect of neuroticism on this causal association. This study proves the protective role of serum albumin for neuroticism and the riskiness of personality traits for suicidal ideation in individuals with depression.

7.
Infect Dis Poverty ; 13(1): 37, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783378

ABSTRACT

Natural, geographical barriers have historically limited the spread of communicable diseases. This is no longer the case in today's interconnected world, paired with its unprecedented environmental and climate change, emphasising the intersection of evolutionary biology, epidemiology and geography (i.e. biogeography). A total of 14 articles of the special issue entitled "Geography and health: role of human translocation and access to care" document enhanced disease transmission of diseases, such as malaria, leishmaniasis, schistosomiasis, COVID-19 (Severe acute respiratory syndrome corona 2) and Oropouche fever in spite of spatiotemporal surveillance. High-resolution satellite images can be used to understand spatial distributions of transmission risks and disease spread and to highlight the major avenue increasing the incidence and geographic range of zoonoses represented by spill-over transmission of coronaviruses from bats to pigs or civets. Climate change and globalization have increased the spread and establishment of invasive mosquitoes in non-tropical areas leading to emerging outbreaks of infections warranting improved physical, chemical and biological vector control strategies. The translocation of pathogens and their vectors is closely connected with human mobility, migration and the global transport of goods. Other contributing factors are deforestation with urbanization encroaching into wildlife zones. The destruction of natural ecosystems, coupled with low income and socioeconomic status, increase transmission probability of neglected tropical and zoonotic diseases. The articles in this special issue document emerging or re-emerging diseases and surveillance of fever symptoms. Health equity is intricately connected to accessibility to health care and the targeting of healthcare resources, necessitating a spatial approach. Public health comprises successful disease management integrating spatial surveillance systems, including access to sanitation facilities. Antimicrobial resistance caused, e.g. by increased use of antibiotics in health, agriculture and aquaculture, or acquisition of resistance genes, can be spread by horizontal gene transfer. This editorial reviews the key findings of this 14-article special issue, identifies important gaps relevant to our interconnected world and makes a number of specific recommendations to mitigate the transmission risks of infectious diseases in the post-COVID-19 pandemic era.


Subject(s)
Health Services Accessibility , Zoonoses , Humans , Animals , Zoonoses/epidemiology , COVID-19/transmission , COVID-19/epidemiology , Communicable Diseases/epidemiology , Communicable Diseases/transmission , SARS-CoV-2 , Geography
8.
Front Immunol ; 15: 1388690, 2024.
Article in English | MEDLINE | ID: mdl-38803495

ABSTRACT

Introduction: Psoriasis is a chronic skin disease characterized by unique scaling plaques. However, during the acute phase, psoriatic lesions exhibit eczematous changes, making them difficult to distinguish from atopic dermatitis, which poses challenges for the selection of biological agents. This study aimed to identify potential diagnostic genes in psoriatic lesions and investigate their clinical significance. Methods: GSE182740 datasets from the GEO database were analyzed for differential analysis; machine learning algorithms (SVM-RFE and LASSO regression models) are used to screen for diagnostic markers; CIBERSORTx is used to determine the dynamic changes of 22 different immune cell components in normal skin lesions, psoriatic non-lesional skin, and psoriatic lesional skin, as well as the expression of the diagnostic genes in 10 major immune cells, and real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry are used to validate results. Results: We obtained 580 differentially expressed genes (DEGs) in the skin lesion and non-lesion of psoriasis patients, 813 DEGs in mixed patients between non-lesions and lesions, and 96 DEGs in the skin lesion and non-lesion of atopic dermatitis, respectively. Then 144 specific DEGs in psoriasis via a Veen diagram were identified. Ultimately, UGGT1, CCNE1, MMP9 and ARHGEF28 are identified for potential diagnostic genes from these 144 specific DEGs. The value of the selected diagnostic genes was verified by receiver operating characteristic (ROC) curves with expanded samples. The the area under the ROC curve (AUC) exceeded 0.7 for the four diagnosis genes. RT-qPCR results showed that compared to normal human epidermis, the expression of UGGT1, CCNE1, and MMP9 was significantly increased in patients with psoriasis, while ARHGEF28 expression was significantly decreased. Notably, the results of CIBERSORTx showed that CCNE1 was highly expressed in CD4+ T cells and neutrophils, ARHGEF28 was also expressed in mast cells. Additionally, CCNE1 was strongly correlated with IL-17/CXCL8/9/10 and CCL20. Immunohistochemical results showed increased nuclear expression of CCNE1 in psoriatic epidermal cells relative to normal. Conclusion: Based on the performance of the four genes in ROC curves and their expression in immune cells from patients with psoriasis, we suggest that CCNE1 possess higher diagnostic value.


Subject(s)
Biomarkers , Machine Learning , Psoriasis , Skin , Psoriasis/immunology , Psoriasis/diagnosis , Psoriasis/genetics , Humans , Skin/immunology , Skin/pathology , Skin/metabolism , Gene Expression Profiling , Dermatitis, Atopic/immunology , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/genetics , Transcriptome , Databases, Genetic , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Oncogene Proteins , Cyclin E
10.
BMC Public Health ; 24(1): 1401, 2024 May 26.
Article in English | MEDLINE | ID: mdl-38797861

ABSTRACT

BACKGROUND: The vaccination status of post-stroke patients, who are at high risk of severe outcomes from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a significant concern, yet it remains unclear. We aimed to explore the vaccination status, factors associated with vaccine hesitancy, and adverse effects after vaccination among post-stroke patients. METHODS: This multi-center observational study enrolled hospitalized post-stroke patients from six Chinese hospitals (Oct 1, 2020 - Mar 31, 2021), examining vaccine uptake and self-reported reasons for vaccine hesitancy, utilizing logistic regression to investigate risk factors for vaccine hesitancy, and recording any adverse reactions post-vaccination. RESULTS: Of the total 710 post-stroke patients included in the study, 430 (60.6%) had completed the recommended full-3 dose SARS-CoV-2 vaccination, with 176 (24.8%) remaining unvaccinated. The most common reasons for vaccine hesitancy were concerns about vaccine side effects (41.5%) and impaired mobility (33.9%). Logistic regression identified advanced age (aOR = 1.97, 95%CI: 1.36-2.85, P = 0.001), lower Barthel Index score (aOR = 0.88, 95%CI: 0.82-0.93, P = 0.018), higher Modified Rankin Scale score (aOR = 1.85, 95%CI: 1.32-2.56, P = 0.004), and poorer usual activity level of EuroQol 5-Dimension (aOR = 2.82, 95%CI: 1.51-5.28, P = 0.001) as independent risk factors for vaccine hesitancy. Approximately 14.8% reported minor adverse reactions, mainly pain at the injection site. CONCLUSION: We found that post-stroke patients have insufficient SARS-CoV-2 vaccination rates, with key risk factors for vaccine hesitancy including concerns about side effects, advanced age, and functional impairments. No severe adverse reactions were observed among the vaccinated population.


Subject(s)
COVID-19 Vaccines , COVID-19 , Stroke , Vaccination Hesitancy , Humans , Male , Female , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Middle Aged , Cross-Sectional Studies , Aged , COVID-19/prevention & control , COVID-19/psychology , Vaccination Hesitancy/psychology , Vaccination Hesitancy/statistics & numerical data , Stroke/psychology , China , Risk Factors , SARS-CoV-2
11.
BMC Plant Biol ; 24(1): 457, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38797823

ABSTRACT

BACKGROUND: Cotton is globally important crop. Verticillium wilt (VW), caused by Verticillium dahliae, is the most destructive disease in cotton, reducing yield and fiber quality by over 50% of cotton acreage. Breeding resistant cotton cultivars has proven to be an efficient strategy for improving the resistance of cotton to V. dahliae. However, the lack of understanding of the genetic basis of VW resistance may hinder the progress in deploying elite cultivars with proven resistance. RESULTS: We planted the VW-resistant Gossypium hirsutum cultivar Zhongzhimian No.2 (ZZM2) in an artificial greenhouse and disease nursery. ZZM2 cotton was subsequently subjected to transcriptome sequencing after Vd991 inoculation (6, 12, 24, 48, and 72 h post-inoculation). Several differentially expressed genes (DEGs) were identified in response to V. dahliae infection, mainly involved in resistance processes, such as flavonoid and terpenoid quinone biosynthesis, plant hormone signaling, MAPK signaling, phenylpropanoid biosynthesis, and pyruvate metabolism. Compared to the susceptible cultivar Junmian No.1 (J1), oxidoreductase activity and reactive oxygen species (ROS) production were significantly increased in ZZM2. Furthermore, gene silencing of cytochrome c oxidase subunit 1 (COX1), which is involved in the oxidation-reduction process in ZZM2, compromised its resistance to V. dahliae, suggesting that COX1 contributes to VW resistance in ZZM2. CONCLUSIONS: Our data demonstrate that the G. hirsutum cultivar ZZM2 responds to V. dahliae inoculation through resistance-related processes, especially the oxidation-reduction process. This enhances our understanding of the mechanisms regulating the ZZM2 defense against VW.


Subject(s)
Disease Resistance , Gene Expression Profiling , Gene Regulatory Networks , Gossypium , Plant Diseases , Gossypium/genetics , Gossypium/microbiology , Gossypium/immunology , Plant Diseases/microbiology , Plant Diseases/genetics , Plant Diseases/immunology , Disease Resistance/genetics , Ascomycota/physiology , Gene Expression Regulation, Plant , Transcriptome , Verticillium
12.
J Antimicrob Chemother ; 79(6): 1423-1431, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38708557

ABSTRACT

BACKGROUND: Bemnifosbuvir (AT-527) is a novel oral guanosine nucleotide antiviral drug for the treatment of persons with COVID-19. Direct assessment of drug disposition in the lungs, via bronchoalveolar lavage, is necessary to ensure antiviral drug levels at the primary site of SARS-CoV-2 infection are achieved. OBJECTIVES: This Phase 1 study in healthy subjects aimed to assess the bronchopulmonary pharmacokinetics, safety and tolerability of repeated doses of bemnifosbuvir. METHODS: A total of 24 subjects were assigned to receive bemnifosbuvir twice daily at doses of 275, 550 or 825 mg for up to 3.5 days. RESULTS: AT-511, the free base of bemnifosbuvir, was largely eliminated from the plasma within 6 h post dose in all dosing groups. Antiviral drug levels of bemnifosbuvir were consistently achieved in the lungs with bemnifosbuvir 550 mg twice daily. The mean level of the guanosine nucleoside metabolite AT-273, the surrogate of the active triphosphate metabolite of the drug, measured in the epithelial lining fluid of the lungs was 0.62 µM at 4-5 h post dose. This exceeded the target in vitro 90% effective concentration (EC90) of 0.5 µM for antiviral drug exposure against SARS-CoV-2 replication in human airway epithelial cells. Bemnifosbuvir was well tolerated across all doses tested, and most treatment-emergent adverse events reported were mild in severity and resolved. CONCLUSIONS: The favourable pharmacokinetics and safety profile of bemnifosbuvir demonstrates its potential as an oral antiviral treatment for COVID-19, with 550 mg bemnifosbuvir twice daily currently under further clinical evaluation in persons with COVID-19.


Subject(s)
Antiviral Agents , COVID-19 Drug Treatment , Prodrugs , SARS-CoV-2 , Humans , Antiviral Agents/pharmacokinetics , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Male , Adult , Prodrugs/pharmacokinetics , Prodrugs/administration & dosage , Female , SARS-CoV-2/drug effects , Middle Aged , Administration, Oral , COVID-19 , Young Adult , Lung/drug effects , Lung/metabolism , Lung/virology , Healthy Volunteers , Guanosine/analogs & derivatives , Guanosine/pharmacokinetics , Guanosine/administration & dosage
13.
Front Physiol ; 15: 1337754, 2024.
Article in English | MEDLINE | ID: mdl-38699145

ABSTRACT

Purpose: Sacroiliac joint dysfunction (SIJD), while being the primary contributor to low back pain, is still disregarded and treated as low back pain. Mulligan's Mobilization with Movement (MWM) Techniques and Core Stability Exercises (CSE) are often used to treat low back pain. There is not much evidence that it is effective in SIJD. To evaluate the effectiveness of CSE coupled with MWM (CSE + MWM) in the treatment of SIJD. Methods: 39 patients with SIJD were recruited and randomly divided into distinct groups as follows: control group (n = 13), CSE group (n = 13) and CSE + MWM group (n = 13). The Numerical Pain Rating Scale (NPRS), the Roland Morris Disability Questionnaire (RMDQ), the Range of Motion (ROM), the Pressure Pain Threshold (PPT) and the pelvic tilt angle asymmetry ratio in the sagittal plane (PTAR) were used to gauge the intervention's success both before (M0) and after (M1) it. All experimental data were statistically analyzed. Results: The SIJ-related pain metric significantly decreased in both the CSE + MWM group and the CSE group between M0 and M1, as determined by the NPRS and RMDQ. Between M0 and M1, The CSE group's left axial rotation ROM and lumbar flexion ROM were significantly decreased. The CSE + MWM group's extension ROM and left lateral flexion ROM both significantly increased between M0 and M1. In the difference variable (M1-M0), the CSE + MWM group substantially outperformed control group in the left lateral flexion ROM and outperformed the CSE group in the left axial rotation ROM. Conclusion: In individuals with SIJD, CSE + MWM is beneficial in lowering pain, disability, and function. Treatment with CSE and MWM approaches for SIJ appears to boost this efficacy.

14.
Ann Jt ; 9: 13, 2024.
Article in English | MEDLINE | ID: mdl-38690073

ABSTRACT

Background: Rheumatoid arthritis (RA), a systemic autoimmune disease with approximately 1% prevalent population worldwide, which the etiology is still unclear. RA cannot be completely cured at present, which seriously affects the quality of life of patients. This study is to compare the peripheral blood α-L-fucosidase (AFU) between RA and healthy persons. Methods: A cross-sectional study was performed using total of 96 patients with RA served as case group and another 94 age-matched healthy volunteers served as a control group. AFU assay is detected by continuous monitoring method using Toshiba TBA-120FR (Tokyo, Japan) fully automatic biochemical analyzer in Japan, and the reagent is purchased from Zhejiang Quark Biological Company (Zhejiang, China). Statistical analysis was performed using SPSS 24.0 (SPSS, Inc., Chicago, IL, USA). Results: AFU activity in peripheral blood of RA patients were lower than healthy controls. The higher AFU activity, the shorter the course of disease (r=-0.2790, P=0.0065). The activity of lactate dehydrogenase in patients with RA is higher than that of healthy control, but the activity of acetylcholinesterase is lower than that of normal people. Finally, AFU activity was negatively correlated with the activity of lactate dehydrogenase (r=-0.2381, P=0.0208) and positively correlated with the activity of acetylcholinesterase (r=0.2985, P=0.0035). Conclusions: Changes of peripheral blood AFU activity might be associated with progression of disease in RA patients. The changes of AFU activity may lead to disturbances in glucose and lipid metabolism.

15.
Biometrics ; 80(2)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38708764

ABSTRACT

When studying the treatment effect on time-to-event outcomes, it is common that some individuals never experience failure events, which suggests that they have been cured. However, the cure status may not be observed due to censoring which makes it challenging to define treatment effects. Current methods mainly focus on estimating model parameters in various cure models, ultimately leading to a lack of causal interpretations. To address this issue, we propose 2 causal estimands, the timewise risk difference and mean survival time difference, in the always-uncured based on principal stratification as a complement to the treatment effect on cure rates. These estimands allow us to study the treatment effects on failure times in the always-uncured subpopulation. We show the identifiability using a substitutional variable for the potential cure status under ignorable treatment assignment mechanism, these 2 estimands are identifiable. We also provide estimation methods using mixture cure models. We applied our approach to an observational study that compared the leukemia-free survival rates of different transplantation types to cure acute lymphoblastic leukemia. Our proposed approach yielded insightful results that can be used to inform future treatment decisions.


Subject(s)
Models, Statistical , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Causality , Biometry/methods , Treatment Outcome , Computer Simulation , Disease-Free Survival , Survival Analysis
17.
Langmuir ; 40(18): 9717-9724, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38712354

ABSTRACT

Connectivity isomerization of the same aromatic molecular core with different substitution positions profoundly affects electron transport pathways and single-molecule conductance. Herein, we designed and synthesized all connectivity isomers of a thiophene (TP) aromatic ring substituted by two dihydrobenzo[b]thiophene (BT) groups with ethynyl spacers (m,n-TP-BT, (m,n = 2,3; 2,4; 2,5; 3,4)), to systematically probe how connectivity contributes to single-molecule conductance. Single-molecule conductance measurements using a scanning tunneling microscopy break junction (STM-BJ) technique show ∼12-fold change in conductance values, which follow an order of 10-4.83 G0 (2,4-TP-BT) < 10-4.78 G0 (3,4-TP-BT) < 10-4.06 G0 (2,3-TP-BT) < 10-3.75 G0 (2,5-TP-BT). Electronic structure analysis and theoretical simulations show that the connectivity isomerization significantly changes electron delocalization and HOMO-LUMO energy gaps. Moreover, the connectivity-dependent molecular structures lead to different quantum interference (QI) effects in electron transport, e.g., a strong destructive QI near E = EF leads the smallest conductance value for 2,4-TP-BT. This work proves a clear relationship between the connectivity isomerization and single-molecule conductance of thiophene heterocyclic molecular junctions for the future design of molecular devices.

18.
Biometrics ; 80(2)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38742906

ABSTRACT

Semicompeting risks refer to the phenomenon that the terminal event (such as death) can censor the nonterminal event (such as disease progression) but not vice versa. The treatment effect on the terminal event can be delivered either directly following the treatment or indirectly through the nonterminal event. We consider 2 strategies to decompose the total effect into a direct effect and an indirect effect under the framework of mediation analysis in completely randomized experiments by adjusting the prevalence and hazard of nonterminal events, respectively. They require slightly different assumptions on cross-world quantities to achieve identifiability. We establish asymptotic properties for the estimated counterfactual cumulative incidences and decomposed treatment effects. We illustrate the subtle difference between these 2 decompositions through simulation studies and two real-data applications in the Supplementary Materials.


Subject(s)
Computer Simulation , Humans , Models, Statistical , Risk , Randomized Controlled Trials as Topic/statistics & numerical data , Mediation Analysis , Treatment Outcome , Biometry/methods
19.
Front Cell Dev Biol ; 12: 1343938, 2024.
Article in English | MEDLINE | ID: mdl-38745861

ABSTRACT

This review examines the complex role of Pin1 in the development and treatment of cancer. Pin1 is the only peptidyl-prolyl isomerase (PPIase) that can recognize and isomerize phosphorylated Ser/Thr-Pro peptide bonds. Pin1 catalyzes a structural change in phosphorylated Ser/Thr-Pro motifs that can modulate protein function and thereby impact cell cycle regulation and tumorigenesis. The molecular mechanisms by which Pin1 contributes to oncogenesis are reviewed, including Pin1 overexpression and its correlation with poor cancer prognosis, and the contribution of Pin1 to aggressive tumor phenotypes involved in therapeutic resistance is discussed, with an emphasis on cancer stem cells, the epithelial-to-mesenchymal transition (EMT), and immunosuppression. The therapeutic potential of Pin1 inhibition in cancer is discussed, along with the promise and the difficulties in identifying potent, drug-like, small-molecule Pin1 inhibitors. The available evidence supports the efficacy of targeting Pin1 as a novel cancer therapeutic by analyzing the role of Pin1 in a complex network of cancer-driving pathways and illustrating the potential of synergistic drug combinations with Pin1 inhibitors for treating aggressive and drug-resistant tumors.

20.
J Thorac Dis ; 16(4): 2379-2393, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38738238

ABSTRACT

Background: Data regarding the safety and efficacy of delayed completion lobectomy (CL) following sublobar resections remain scant. We evaluated the technical difficulty and short-term outcomes of CL occurring at least 3 months following the anatomical segmentectomy or wedge resection. Methods: Consecutive non-small cell lung cancer (NSCLC) patients who underwent a second resection within the same lobe at least 3 months after their initial resection from January 2013 to December 2019 at the Shanghai Pulmonary Hospital were retrospectively included. The patients were divided into a segmentectomy group (SG group) and a wedge resection group (WR group) based on their initial resection strategy. Baseline characteristics and short-term outcomes after CL between the two groups were compared. Results: Twenty-five patients undergoing CL were included, nine in the SG group and 16 in the WR group. No deaths occurred within 30 days postoperatively, and the rate of overall postoperative complications was 28.0% (7/25). Statistically significant differences were found in rates of postoperative complications between the two groups (SG: 55.6% vs. WR: 12.5%, P=0.03) and in the use of bronchoplasty or angioplasty during the CL (SG: 33.3% vs. WR: 0.0%, P=0.04). After CL, no significant differences were found in 5-year recurrence-free survival (RFS) (WR: 66.7% vs. SG: 61.0%, P=0.31) or overall survival (OS) (WR: 93.8% vs. SG: 66.7%, P=0.06) between two groups. Conclusions: Delayed CL occurring over 3 months after sublobar resection is a safe and effective procedure, with no deaths occurring within 30 days postoperatively. As compared to a segmentectomy at the time of the index operation, a wedge resection may portend less morbidity, with a decreased risk of needing adjunctive bronchoplasty or angioplasty procedures during CL. After CL, 5-year RFS and OS were comparable between WR and SG groups.

SELECTION OF CITATIONS
SEARCH DETAIL
...