Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 27
Filter
Add more filters

Country/Region as subject
Publication year range
1.
Immunity ; 56(1): 207-223.e8, 2023 01 10.
Article in English | MEDLINE | ID: mdl-36580919

ABSTRACT

Tissue-resident memory CD8+ T (TRM) cells are a subset of memory T cells that play a critical role in limiting early pathogen spread and controlling infection. TRM cells exhibit differences across tissues, but their potential heterogeneity among distinct anatomic compartments within the small intestine and colon has not been well recognized. Here, by analyzing TRM cells from the lamina propria and epithelial compartments of the small intestine and colon, we showed that intestinal TRM cells exhibited distinctive patterns of cytokine and granzyme expression along with substantial transcriptional, epigenetic, and functional heterogeneity. The T-box transcription factor Eomes, which represses TRM cell formation in some tissues, exhibited unexpected context-specific regulatory roles in supporting the maintenance of established TRM cells in the small intestine, but not in the colon. Taken together, these data provide previously unappreciated insights into the heterogeneity and differential requirements for the formation vs. maintenance of intestinal TRM cells.


Subject(s)
CD8-Positive T-Lymphocytes , Memory T Cells , CD8-Positive T-Lymphocytes/metabolism , Immunologic Memory , Intestine, Small , Colon
2.
PLoS Biol ; 21(1): e3001983, 2023 01.
Article in English | MEDLINE | ID: mdl-36716323

ABSTRACT

During a microbial infection, responding CD8+ T cells give rise to effector cells that provide acute host defense and memory cells that provide sustained protection. An alternative outcome is exhaustion, a state of T cell dysfunction that occurs in the context of chronic infections and cancer. Although it is evident that exhausted CD8+ T (TEX) cells are phenotypically and molecularly distinct from effector and memory CD8+ T cells, the factors regulating the earliest events in the differentiation process of TEX cells remain incompletely understood. Here, we performed single-cell RNA-sequencing and single-cell ATAC-sequencing of CD8+ T cells responding to LCMV-Armstrong (LCMV-Arm) or LCMV-Clone 13 (LCMV-Cl13), which result in acute or chronic infections, respectively. Compared to CD8+ T cells that had undergone their first division in response to LCMV-Arm (Div1ARM) cells, CD8+ T cells that had undergone their first division in response to LCMV-Cl13 (Div1CL13) expressed higher levels of genes encoding transcription factors previously associated with exhaustion, along with higher levels of Ezh2, the catalytic component of the Polycomb Repressive Complex 2 (PRC2) complex, which mediates epigenetic silencing. Modulation of Ezh2 resulted in altered expression of exhaustion-associated molecules by CD8+ T cells responding to LCMV-Cl13, though the specific cellular and infectious contexts, rather than simply the level of Ezh2 expression, likely determine the eventual outcome. Taken together, these findings suggest that the differentiation paths of CD8+ T cells responding to acute versus chronic infections may diverge earlier than previously appreciated.


Subject(s)
Lymphocytic Choriomeningitis , Humans , Animals , Mice , Lymphocytic Choriomeningitis/genetics , Lymphocytic Choriomeningitis/metabolism , Persistent Infection , CD8-Positive T-Lymphocytes/metabolism , Lymphocytic choriomeningitis virus , Epigenesis, Genetic , Mice, Inbred C57BL
3.
Support Care Cancer ; 32(9): 624, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39222130

ABSTRACT

PURPOSE: The Palliative Care Outcomes Collaboration (PCOC) aims to enhance patient outcomes systematically. However, identifying crucial items and accurately determining PCOC phases remain challenging. This study aims to identify essential PCOC data items and construct a prediction model to accurately classify PCOC phases in terminal patients. METHODS: A retrospective cohort study assessed PCOC data items across four PCOC phases: stable, unstable, deteriorating, and terminal. From July 2020 to March 2023, terminal patients were enrolled. A multinomial mixed-effect regression model was used for the analysis of multivariate PCOC repeated measurement data. RESULTS: The dataset comprised 1933 terminally ill patients from 4 different hospice service settings. A total of 13,219 phases of care were analyzed. There were significant differences in the symptom assessment scale, palliative care problem severity score, Australia-modified Karnofsky performance status, and resource utilization groups-activities of daily living among the four PCOC phases of care. Clinical needs, including pain and other symptoms, declined from unstable to terminal phases, while psychological/spiritual and functional status for bed mobility, eating, and transfers increased. A robust prediction model achieved areas under the curves (AUCs) of 0.94, 0.94, 0.920, and 0.96 for stable, unstable, deteriorating, and terminal phases, respectively. CONCLUSIONS: Critical PCOC items distinguishing between PCOC phases were identified, enabling the development of an accurate prediction model. This model enhances hospice care quality by facilitating timely interventions and adjustments based on patients' PCOC phases.


Subject(s)
Hospice Care , Palliative Care , Humans , Retrospective Studies , Male , Female , Hospice Care/methods , Aged , Palliative Care/methods , Middle Aged , Aged, 80 and over , Regression Analysis , Cohort Studies , Adult , Activities of Daily Living , Karnofsky Performance Status
4.
Rev Cardiovasc Med ; 23(7): 242, 2022 Jul.
Article in English | MEDLINE | ID: mdl-39076927

ABSTRACT

Background: Atrial fibrillation (AF) is associated with an increased risk of heart failure, death and thromboembolism. AF is prevalent in patients with cancer. Although current guidelines suggest the application of oral anticoagulants (OACs) for thromboembolic event prevention in high-risk AF patients, owing to the high thromboembolic and bleeding risks of active-cancer patients, there is no consensus on the use of OACs in such a population. Therefore, we conducted this retrospective cohort study to investigate the applicability of the CHA 2 DS 2 -VASc score and to evaluate the efficacy and safety outcomes of OAC therapy in active-cancer patients with AF. Methods: This retrospective cohort study enrolled patients diagnosed with cancer at National Cheng Kung University Hospital between November 2012 and August 2019. The primary outcomes included all-cause mortality, thromboembolic events (stroke/transient ischemic attack and systemic emboli), acute myocardial infarction (AMI), hospitalization for HF and major bleeding events. Results: We enrolled 2429 patients with active cancer. Among these patients, 1060 patients (43.6%) had AF. After 1:2 propensity score matching, 690 cancer patients with AF were enrolled for the final analysis, grouped as follows: 225 patients taking OACs and 465 patients without OAC treatment. The OAC-treated group had lower all-cause mortality than the patients without OAC treatment (all-cause mortality rate in OAC treatment vs. non-OAC treatment: 24.4% vs. 37.4%, hazard ratio 0.58 [95% confidence interval (CI) 0.43-0.78], p < 0.001). However, there was no difference in thromboembolic events, myocardial infarction or heart failure hospitalization between the OAC-treated and non-OAC-treated groups. Importantly, the risk of major bleeding composition (i.e., major gastrointestinal bleeding and intracranial hemorrhage) was similar between these two groups. Moreover, the CHA 2 DS 2 -VASc score could not predict thromboembolic events in the enrolled active-cancer patients with AF (OR 1.23, 95% CI 0.98-1.56). Conclusions: OAC treatment may significantly reduce the risk of death, without safety concerns, in active-cancer patients with AF. OAC treatment may not prevent thromboembolic events in patients with active cancer and AF. However, we found that OAC treatment is associated with improved prognosis without increasing the risks of major bleeding, despite several limitations in this study. Further studies are required to determine the optimal use of anticoagulation therapy in this high-risk population.

5.
Arch Phys Med Rehabil ; 98(9): 1836-1841, 2017 09.
Article in English | MEDLINE | ID: mdl-28254639

ABSTRACT

OBJECTIVE: To examine the psychometric and clinimetric properties of the Melbourne Assessment 2 (MA2), an outcome measurement that is increasingly used in clinical studies. DESIGN: Psychometric and clinimetric study. SETTING: Community. PARTICIPANTS: Seventeen children with cerebral palsy (CP) from 5 to 12 years were recruited for the estimation of the test-retest reliability and minimal detectable change (MDC). Thirty-five children with CP were recruited to receive an 8-week intensive neurorehabilitation intervention to estimate the validity, responsiveness, and minimal clinically important difference (MCID). INTERVENTIONS: Thirty-five children with CP received upper limb neurorehabilitation programs for 8 weeks. MAIN OUTCOME MEASURES: The MA2 and the criterion measures, including the Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition (BOT-2), the Box and Blocks Test (BBT), and the Pediatric Motor Activity Log-Revised (PMAL-R), were evaluated at pretreatment and posttreatment. RESULTS: The MA2 has 4 subscales: range of motion, fluency, accuracy, and dexterity. The test-retest reliability of the MA2 is high (intraclass correlation coefficient, .92-.98). The significant relationships between the MA2 and BBT, BOT-2, and PMAL-R support its validity. The significance of paired t test results (P<.001) and large magnitudes of the standardized response mean (1.70-2.00) confirm the responsiveness of the MA2. The MDC values of the 4 subscales of the MA2 are 2.85, 1.63, 1.97, and 1.84, respectively, and the suggested MCID values of these 4 subscales are 2.35, 3.20, 2.09, and 2.22, respectively, indicating the minimum scores of improvement to be interpreted as both statistically significant and clinically important. CONCLUSIONS: The study findings indicate that the MA2 has sound psychometric and clinimetric properties and is thus an adequate measurement for research and clinical applications.


Subject(s)
Cerebral Palsy/psychology , Cerebral Palsy/rehabilitation , Disability Evaluation , Minimal Clinically Important Difference , Child , Child, Preschool , Female , Humans , Male , Neurological Rehabilitation/methods , Neurological Rehabilitation/statistics & numerical data , Psychometrics , Reproducibility of Results , Treatment Outcome , Upper Extremity , Victoria
6.
Cell Microbiol ; 17(12): 1742-51, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26432982

ABSTRACT

The Type VI secretion system is a widespread bacterial nanomachine, used to deliver toxins directly into eukaryotic or prokaryotic target cells. These secreted toxins, or effectors, act on diverse cellular targets, and their action provides the attacking bacterial cell with a significant fitness advantage, either against rival bacteria or eukaryotic host organisms. In this review, we discuss the delivery of diverse effectors by the Type VI secretion system, the modes of action of the so-called 'anti-bacterial' and 'anti-eukaryotic' effectors, the mechanism of self-resistance against anti-bacterial effectors and the evolutionary implications of horizontal transfer of Type VI secretion system-associated toxins. Whilst it is likely that many more effectors remain to be identified, it is already clear that toxins delivered by this secretion system represent efficient weapons against both bacteria and eukaryotes.


Subject(s)
Bacteria/pathogenicity , Bacterial Toxins/metabolism , Eukaryotic Cells/microbiology , Eukaryotic Cells/physiology , Type VI Secretion Systems/metabolism , Virulence Factors/metabolism , Antibiosis , Bacteria/metabolism , Cell Survival/drug effects , Microbial Viability/drug effects , Virulence
7.
JAMA Netw Open ; 7(10): e2441765, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39476235

ABSTRACT

Importance: Cardiovascular disease (CVD) can be recurrent during type 2 diabetes (T2D) progression in this aging population. The effectiveness of sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy on total (ie, first and subsequent) CVD among patients with T2D in clinical practice remains uncertain. Objective: To analyze the comparative association of SGLT2i vs dipeptidyl peptidase 4 inhibitor (DPP4i) therapy with total CVD among patients with T2D in clinical practice. Design, Setting, and Participants: This retrospective cohort study used electronic medical records at the National Cheng Kung University Hospital, a leading medical center in Taiwan, from 2015 through 2021. Adult patients with T2D who initiated first use of the study drugs from 2016 through 2019, with up to 6 years of follow-up, were identified. Main Outcomes and Measures: The primary outcomes included total composite CVD events and individual CVD subtypes (ie, atrial fibrillation, coronary heart disease, heart failure, stroke, myocardial infarction, and transient ischemic attack). A shared frailty model analysis was used to assess the association of treatment with repeat CVD events. Data from patients at high risk for CVD recurrence were further analyzed. Data were analyzed from September 1, 2022, to December 31, 2023. Results: Overall, 8384 patients with T2D were identified (mean [SD] age, 63.7 [12.4] years; 4645 [55.4%] male). A total of 1632 propensity score-matched pairs of SGLT2i (mean [SD] age, 57.8 [12.0] years; 673 [41.2%] female and 959 [58.8%] male) and DPP4i (mean [SD] age, 58.2 [12.9] years; 655 [40.1%] female and 977 [59.9%] male) users were included. SGLT2i was associated with reduced total CVD risk vs DPP4i therapy (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98]) but not the first CVD event (with the use of SGLT2i therapy were more prominent for patients at high risk of CVD (ie, HR, 0.70 [95% CI, 0.62-0.80] for individuals with estimated glomerular filtration rate lower than 60 mL/min/1.73 m2; HR, 0.70 [95% CI, 0.64-0.78]; for individuals having any diabetes-related complications; and HR, 0.72 [95% CI, 0.65-0.80] for individuals with a history of CVD) compared with the overall cohort. Among patients at high risk of CVD, greater reduced total CVD burden associated with SGLT2i therapy was observed for women vs men (eg, HR, 0.59 [95% CI, 0.49-0.72] in the subgroup with CVD history). Conclusions and Relevance: In this cohort study of patients with T2D, the use of SGLT2is vs DPP4is was associated with reduced total cardiovascular burden, suggesting that long-term use of this therapy may optimize treatment benefit among patients with chronic CVD. The SGLT2i-associated benefit among patients with high risk of CVD encourages the prioritization of SGLT2i use for these vulnerable individuals.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Sodium-Glucose Transporter 2 Inhibitors , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Male , Female , Middle Aged , Retrospective Studies , Cardiovascular Diseases/epidemiology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Aged , Taiwan/epidemiology , Heart Disease Risk Factors , Risk Factors
8.
J Appl Stat ; 50(10): 2151-2170, 2023.
Article in English | MEDLINE | ID: mdl-37434630

ABSTRACT

Incidence rates for diseases are widely used in the field of medical research because they lead to clear and simple physical and clinical interpretations. In this study, we propose an efficient estimation method that incorporates auxiliary subgroup information related to the incidence rate into the estimation of the Cox proportional hazard model. The results show that utilizing the incidence rate information improves the efficiency of the estimation of regression parameters based on the double empirical likelihood method compared to that for conventional models that do not incorporation such information. We show that estimators of regression parameters asymptotically follow a multivariate normal distribution with a variance-covariance matrix that can be consistently estimated. Simulation results indicate that the proposed estimators significantly increase efficiency. Finally, an example of the effects of type 2 diabetes on stroke is applied to demonstrate the proposed method.

9.
Neurorehabil Neural Repair ; 37(2-3): 109-118, 2023.
Article in English | MEDLINE | ID: mdl-36987387

ABSTRACT

BACKGROUND: Previous studies have compared the effectiveness of constraint-induced movement therapy (CIMT) by different training doses. However, whether the dosing schedule, that is, intensive or distributed, influences the effectiveness of CIMT in children with unilateral cerebral palsy (CP) is unknown. OBJECTIVE: To investigate the effectiveness of intensive and distributed CIMT for children with unilateral CP. METHODS: Fifty children with unilateral CP were assigned to intensive or distributed CIMT group with a total of 36 training hours. The intensive CIMT was delivered within 1 week, and the distributed CIMT was delivered twice a week for 8 weeks. The outcomes were the Melbourne Assessment 2, Box and Block Test, Pediatric Motor Activity Log-Revised (PMAL-R), Bruininks-Oseretsky test of motor proficiency 2, ABILHAND-Kids and Parenting Stress Index-Short Form. The intensive group was assessed at the initiation of treatment (week 0), at the end of 1 week treatment (week 1), and 8 weeks after the initiation of treatment (week 8). The distributed group was assessed at week 0 and week 8. RESULTS: The within-group analyses demonstrated significant differences on all motor outcomes. There were no significant between-group differences at post-treatment, while the intensive CIMT demonstrated larger improvements than the distributed CIMT did on quality of use of the more-affected hand, as rated by parents on the PMAL-R at week 8. CONCLUSIONS: The 2 dosing schedules of CIMT had similar effectiveness for children with unilateral CP. The intensive CIMT yielded additional improvement on parent rated motor quality of the more-affected hand at 8 weeks after the initiation of treatment. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT03128385).


Subject(s)
Cerebral Palsy , Humans , Child , Cerebral Palsy/therapy , Physical Therapy Modalities , Hand , Upper Extremity , Treatment Outcome
10.
Occup Ther Int ; 2023: 8013086, 2023.
Article in English | MEDLINE | ID: mdl-37265856

ABSTRACT

Introduction: Assessment of clinical competence is a significant part of the training for young occupational therapists (OTs). Objective and systematic assessment allows both supervisors and trainees to be aware of the training objectives and monitor the progress. The direct observation of procedural skills (DOPS) is a work-based assessment to evaluate professional knowledge, skills, and attitude in clinical training. This study investigated the perspectives of OT educators and trainees on using DOPS and their discrepancy for OT postgraduate year (PGY) training. Methods: This study used a quantitative online survey. Eighty-six supervisors and 41 trainees of OT PGY training programs from 95 hospitals returned the questionnaire (a 90.5% return rate), and 64 supervisors and 30 trainees who used DOPS were analyzed. Outcomes included the practicality in using the DOPS in clinical settings, the ease of rating the DOPS, and advantages and the disadvantages of the DOPS. Results: Most respondents reported that completing one DOPS required at least 11 minutes for direct observation (11-40 minutes: teacher 92.2%; trainee 80.6%). Most respondents (teacher 96.9%, trainee 96.8%) had feedback after direct observation of DOPS, and about half of the feedback assessments took 5 to 10 minutes (teacher 53.1%, trainee 48.4%). Most OT educators and trainees agreed that clinical resources were sufficient and that DOPS matched with OT training goals, benefited OT competence training, and had a fair, objective, and consistent scoring system. Significantly higher percentages of OT trainees felt stressed in and satisfied with the DOPS assessment than trainers. Differences between teachers and trainees regarding easiness of rating DOPS items were not significant. Conclusion: Most OT educators and trainees agreed that DOPS was a practical and appropriate assessment for OT PGY training.


Subject(s)
Clinical Competence , Occupational Therapy , Humans , Educational Measurement , Taiwan , Surveys and Questionnaires , Perception
11.
Asian J Psychiatr ; 81: 103450, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36630832

ABSTRACT

BACKGROUND: There is a lack of research on the effect of community-based psychiatric rehabilitation programs (CBPRs) in individuals with severe mental illness. This research used data from a retrospective study to examine the effect of a CBPR in a community rehabilitation center. MATERIALS AND METHODS: Clinical outcomes measures from a retrospective study were collected. Outcome measures were the Allen Cognitive Level Screen assessment, Purdue Pegboard Test, Chu's Attention Test, and Activities of Daily Living Rating Scale-III (ADLRS-III) before and immediately after 12 months of intervention. RESULTS: The 141 participants with mental illness were an average age of 35.29 years (SD = 8.75). The retrospective review of medical records showed 46 people dropped out within 12 months, and 95 people continued to participate in the rehabilitation program for 1 year. After 1 year of community rehabilitation, there was a trend for the participants who completed the intervention to improve on the ADLRS-III, Purdue Pegboard Test, and Chu's Attention Test. Participants who performed better on the occupational assessment were more likely to transit to the employment status. CONCLUSION: This study found the benefits of CBPR in work-related intervention for people with mental illness. Occupational assessments are relevant for studying changes in functional outcomes in people with mental illness receiving community-based rehabilitation.


Subject(s)
Mental Disorders , Psychiatric Rehabilitation , Humans , Adult , Retrospective Studies , Activities of Daily Living , Mental Disorders/rehabilitation , Treatment Outcome
12.
Front Med (Lausanne) ; 10: 1052452, 2023.
Article in English | MEDLINE | ID: mdl-37521349

ABSTRACT

Background: Indoor CO2 concentration is an important metric of indoor air quality (IAQ). The dynamic temporal pattern of CO2 levels in intensive care units (ICUs), where healthcare providers experience high cognitive load and occupant numbers are frequently changing, has not been comprehensively characterized. Objective: We attempted to describe the dynamic change in CO2 levels in the ICU using an Internet of Things-based (IoT-based) monitoring system. Specifically, given that the COVID-19 pandemic makes hospital visitation restrictions necessary worldwide, this study aimed to appraise the impact of visitation restrictions on CO2 levels in the ICU. Methods: Since February 2020, an IoT-based intelligent indoor environment monitoring system has been implemented in a 24-bed university hospital ICU, which is symmetrically divided into areas A and B. One sensor was placed at the workstation of each area for continuous monitoring. The data of CO2 and other pollutants (e.g., PM2.5) measured under standard and restricted visitation policies during the COVID-19 pandemic were retrieved for analysis. Additionally, the CO2 levels were compared between workdays and non-working days and between areas A and B. Results: The median CO2 level (interquartile range [IQR]) was 616 (524-682) ppm, and only 979 (0.34%) data points obtained in area A during standard visitation were ≥ 1,000 ppm. The CO2 concentrations were significantly lower during restricted visitation (median [IQR]: 576 [556-596] ppm) than during standard visitation (628 [602-663] ppm; p < 0.001). The PM2.5 concentrations were significantly lower during restricted visitation (median [IQR]: 1 [0-1] µg/m3) than during standard visitation (2 [1-3] µg/m3; p < 0.001). The daily CO2 and PM2.5 levels were relatively low at night and elevated as the occupant number increased during clinical handover and visitation. The CO2 concentrations were significantly higher in area A (median [IQR]: 681 [653-712] ppm) than in area B (524 [504-547] ppm; p < 0.001). The CO2 concentrations were significantly lower on non-working days (median [IQR]: 606 [587-671] ppm) than on workdays (583 [573-600] ppm; p < 0.001). Conclusion: Our study suggests that visitation restrictions during the COVID-19 pandemic may affect CO2 levels in the ICU. Implantation of the IoT-based IAQ sensing network system may facilitate the monitoring of indoor CO2 levels.

13.
Inflamm Bowel Dis ; 29(10): 1602-1612, 2023 10 03.
Article in English | MEDLINE | ID: mdl-37235748

ABSTRACT

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease are 2 types of inflammatory bowel disease (IBD), a group of chronic digestive disorders caused by aberrant immune responses to intestinal microbes. Although changes in the composition of immune cell subsets in the context of IBD have been previously described, the interactions and communication among cells are less well understood. Moreover, the precise mechanisms of action underlying many biologic therapies, including the anti-α4ß7 integrin antagonist vedolizumab, remain incompletely understood. Our study aimed to explore possible additional mechanisms through which vedolizumab acts. METHODS: We performed cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) on peripheral blood and colon immune cells derived from patients with ulcerative colitis treated with the anti-α4ß7 integrin antagonist vedolizumab. We applied a previously published computational approach, NicheNet, to predict immune cell-cell interactions, revealing putative ligand-receptor pairs and key transcriptional changes downstream of these cell-cell communications (CCC). RESULTS: We observed decreased proportions of T helper 17 (TH17) cells in UC patients who responded to vedolizumab and therefore focused the study on identifying cell-cell communications and signals of TH17 cells with other immune cells. For example, we observed that colon TH17 cells from vedolizumab nonresponders were predicted to have a greater degree of interactions with classical monocytes compared with responders, whereas colon TH17 cells from vedolizumab responders exhibited more interactions with myeloid dendritic cells compared with nonresponders. CONCLUSIONS: Overall, our results indicate that efforts to elucidate cell-cell communications among immune and nonimmune cell types may increase the mechanistic understanding of current and investigational therapies for IBD.


Compared to ulcerative patients unresponsive to vedolizumab, immune cell networks of ulcerative colitis patients responsive to vedolizumab have decreased proportion of TH17 and less pro-inflammatory signaling in the gut. Decreased pro-TH17 and interleukin (IL)-1 signaling from classical monocytes and innate immunocytes may mediate this phenotype.


Subject(s)
Colitis, Ulcerative , Inflammatory Bowel Diseases , Humans , Colitis, Ulcerative/drug therapy , Inflammatory Bowel Diseases/drug therapy , Integrins , Cell Communication , Gastrointestinal Agents/therapeutic use , Gastrointestinal Agents/pharmacology
14.
Clin Transl Gastroenterol ; 14(5): e00576, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36854061

ABSTRACT

INTRODUCTION: Crohn's disease (CD) is a major subtype of inflammatory bowel disease (IBD), a spectrum of chronic intestinal disorders caused by dysregulated immune responses to gut microbiota. Although transcriptional and functional changes in a number of immune cell types have been implicated in the pathogenesis of IBD, the cellular interactions and signals that drive these changes have been less well-studied. METHODS: We performed Cellular Indexing of Transcriptomes and Epitopes by sequencing on peripheral blood, colon, and ileal immune cells derived from healthy subjects and patients with CD. We applied a previously published computational approach, NicheNet, to predict immune cell types interacting with CD8 + T-cell subsets, revealing putative ligand-receptor pairs and key transcriptional changes downstream of these cell-cell communications. RESULTS: As a number of recent studies have revealed a potential role for CD8 + T-cell subsets in the pathogenesis of IBD, we focused our analyses on identifying the interactions of CD8 + T-cell subsets with other immune cells in the intestinal tissue microenvironment. We identified ligands and signaling pathways that have implicated in IBD, such as interleukin-1ß, supporting the validity of the approach, along with unexpected ligands, such as granzyme B, which may play previously unappreciated roles in IBD. DISCUSSION: Overall, these findings suggest that future efforts focused on elucidating cell-cell communications among immune and nonimmune cell types may further our understanding of IBD pathogenesis.


Subject(s)
Crohn Disease , Inflammatory Bowel Diseases , Humans , Ligands , Inflammatory Bowel Diseases/metabolism , CD8-Positive T-Lymphocytes/metabolism , Cell Communication
15.
Biomedicines ; 10(2)2022 Feb 01.
Article in English | MEDLINE | ID: mdl-35203549

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent malignant diseases worldwide. Risk prediction for tumor recurrence is important for making effective treatment decisions and for the survival outcomes of patients with CRC after surgery. Herein, we aimed to explore a prediction algorithm and the risk factors for postoperative tumor recurrence using a machine learning (ML) approach with standardized pathology reports for patients with stage II and III CRC. METHODS: Pertinent clinicopathological features were compiled from medical records and standardized pathology reports of patients with stage II and III CRC. Four ML models based on logistic regression (LR), random forest (RF), classification and regression decision trees (CARTs), and support vector machine (SVM) were applied for the development of the prediction algorithm. The area under the curve (AUC) of the ML models was determined in order to compare the prediction accuracy. Genomic studies were performed using a panel-targeted next-generation sequencing approach. RESULTS: A total of 1073 patients who received curative intent surgery at the National Cheng Kung University Hospital between January 2004 and January 2019 were included. Based on conventional statistical methods, chemotherapy (p = 0.003), endophytic tumor configuration (p = 0.008), TNM stage III disease (p < 0.001), pT4 (p < 0.001), pN2 (p < 0.001), increased numbers of lymph node metastases (p < 0.001), higher lymph node ratios (LNR) (p < 0.001), lymphovascular invasion (p < 0.001), perineural invasion (p < 0.001), tumor budding (p = 0.004), and neoadjuvant chemoradiotherapy (p = 0.025) were found to be correlated with the tumor recurrence of patients with stage II-III CRC. While comparing the performance of different ML models for predicting cancer recurrence, the AUCs for LR, RF, CART, and SVM were found to be 0.678, 0.639, 0.593, and 0.581, respectively. The LR model had a better accuracy value of 0.87 and a specificity value of 1 in the testing set. Two prognostic factors, age and LNR, were selected by multivariable analysis and the four ML models. In terms of age, older patients received fewer cycles of chemotherapy and radiotherapy (p < 0.001). Right-sided colon tumors (p = 0.002), larger tumor sizes (p = 0.008) and tumor volumes (p = 0.049), TNM stage II disease (p < 0.001), and advanced pT3-4 stage diseases (p = 0.04) were found to be correlated with the older age of patients. However, pN2 diseases (p = 0.005), lymph node metastasis number (p = 0.001), LNR (p = 0.004), perineural invasion (p = 0.018), and overall survival rate (p < 0.001) were found to be decreased in older patients. Furthermore, PIK3CA and DNMT3A mutations (p = 0.032 and 0.039, respectively) were more frequently found in older patients with stage II-III CRC compared to their younger counterparts. CONCLUSIONS: This study demonstrated that ML models have a comparable predictive power for determining cancer recurrence in patients with stage II-III CRC after surgery. Advanced age and high LNR were significant risk factors for cancer recurrence, as determined by ML algorithms and multivariable analyses. Distinctive genomic profiles may contribute to discrete clinical behaviors and survival outcomes between patients of different age groups. Studies incorporating complete molecular and genomic profiles in cancer prediction models are beneficial for patients with stage II-III CRC.

16.
J Nerv Ment Dis ; 199(7): 513-5, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21716067

ABSTRACT

The aim of this study was to evaluate the intercorrelation between the Personal and Social Performance (PSP) score, cognitive function, and activities of daily living (ADLs). Twenty patients with chronic schizophrenia were recruited; the PSP and ADL scales and psychological assessments including the Wisconsin Card Sorting Test, the Wechsler Memory Scale-Revised (WMS-R), and the Continuous Performance Test (CPT) were administered. Positive correlations between the total PSP scale score and performance in the WMS-R, CPT, and ADL scores were identified. The PSP score was found to be of good reliability for cognitive function and ADL evaluation.


Subject(s)
Activities of Daily Living/psychology , Cognition , Schizophrenic Psychology , Social Adjustment , Adult , Female , Humans , Male , Neuropsychological Tests , Psychiatric Status Rating Scales
17.
Percept Mot Skills ; 112(3): 703-10, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21853759

ABSTRACT

This study investigated the relation of hemispatial inattention to the performance of daily functions in 32 patients with schizophrenia or schizoaffective disorder and in 31 healthy controls. They were tested on the relationship between a target cancellation task and the Activities of Daily Living Rating Scale-II (ADLRS-II). According to the results of the hemispatial inattention test, the patients with schizophrenia made more omissions in the cancellation test than the controls. In addition, the results showed a significant correlation between number of omissions on the cancellation test and the ADLRS-II score in the study participants. A statistically significant relationship was observed between hemispatial inattention and the functional status of patients with schizophrenia, and suggests the need to incorporate measures of visual attention into psychiatric rehabilitation assessments.


Subject(s)
Activities of Daily Living/psychology , Attention , Dominance, Cerebral , Orientation , Perceptual Disorders/diagnosis , Psychotic Disorders/psychology , Schizophrenia/diagnosis , Schizophrenic Psychology , Adult , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Pattern Recognition, Visual , Perceptual Disorders/psychology , Psychomotor Performance , Psychotic Disorders/diagnosis , Young Adult
18.
NPJ Schizophr ; 7(1): 21, 2021 Apr 13.
Article in English | MEDLINE | ID: mdl-33850147

ABSTRACT

Patients with schizophrenia have difficulties in social cognitive domains including emotion recognition and mentalization, and in sensorimotor processing and learning. The relationship between social cognitive deficits and sensorimotor function in patients with schizophrenia remains largely unexplored. With the hypothesis that impaired visual motor processing may decelerate information processing and subsequently affects various domains of social cognition, we examined the association of nonverbal emotion recognition, mentalization, and visual motor processing in schizophrenia. The study examined mentalization using the verbal subset of the Chinese version of Theory of Mind (CToM) Task, an equivalent task of the Faux Pas Test; emotion recognition using the Diagnostic Analysis of Nonverbal Accuracy 2-Taiwan version (DANVA-2-TW), and visual motor processing using a joystick tracking task controlled for basic motor function in 34 individuals with chronic schizophrenia in the community and 42 healthy controls. Patients with schizophrenia had significantly worse performance than healthy controls in social cognition, including facial, prosodic emotion recognition, and mentalization. Visual motor processing was also significantly worse in patients with schizophrenia. Only in patients with schizophrenia, both emotion recognition (mainly in prosodic modality, happy, and sad emotions) and mentalization were positively associated with their learning capacity of visual motor processing. These findings suggest a prospective role of sensorimotor function in their social cognitive deficits. Despite that the underlying neural mechanism needs further research, our findings may provide a new direction for restoration of social cognitive function in schizophrenia by enhancing visual motor processing ability.

19.
Asian J Psychiatr ; 54: 102456, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33271735

ABSTRACT

This study investigated the effect of dual task performance of hand dexterity tasks and the relationship to daily functioning in 40 people with chronic schizophrenia and 35 healthy participants. Participants performed the Purdue Pegboard Test, O'Connor Finger Dexterity Test, and the Serial Subtracting Seven Task as the secondary task under single- and dual-task conditions and completed the Activities of Daily Living Rating Scale-III (ADLRS-III). The hand dexterity of all participants declined from the single to the dual tasks, and the discrepancy between single- and dual-task performance was significantly greater in the schizophrenia group than in the control group. Significant condition and group effects were found for both hand dexterity tests. People with schizophrenia who took longer time in performing hand dexterity tasks had significantly worse daily life function. Negative correlations were noted between discrepancy of dual tasking and the ADLRS-III score in the schizophrenic group. Deficits in dual-task performance of hand dexterity is significant in people with schizophrenia and is related to daily life performance. Occupational therapy practitioners can consider using dual tasks as a therapeutic activity for people with schizophrenia to promote functional abilities in real-world environments.


Subject(s)
Activities of Daily Living , Schizophrenia , Cognition , Fingers , Humans , Motor Skills
SELECTION OF CITATIONS
SEARCH DETAIL