Time Of Disease Diagnosis Research Articles

Watershed regions are more susceptible to tissue microstructural injury in multiple sclerosis.

Histopathologic studies report higher concentrations of multiple sclerosis white matter lesions in watershed areas of the brain, suggesting that areas with relatively lower oxygen levels may be more vulnerable to disease. However, it is unknown at what point in the disease course lesion predilection for watershed territories begins. Accordingly, we studied a cohort of people with newly diagnosed disease and asked whether (1) white matter lesions disproportionally localize to watershed-regions and (2) the degree of microstructural injury in watershed-lesions is more severe. Fifty-four participants, i.e. 38 newly diagnosed people with multiple sclerosis, clinically isolated syndrome or radiologically isolated syndrome, and 16 age- and sex-matched healthy controls underwent brain magnetic resonance imaging. T1-weighted and T2-weighted fluid-attenuated inversion recovery sequences, selective inversion recovery quantitative magnetisation transfer images, and the multi-compartment diffusion imaging with the spherical mean technique were acquired. We computed the macromolecular-to-free pool size ratio, and the apparent axonal volume fraction maps to indirectly estimate myelin and axonal integrity, respectively. We produced a flow territory atlas in each subject's native T2-weighted fluid-attenuated inversion recovery images using a T1-weighted magnetic resonance imaging template in the Montreal Neurological Institute 152 space. Lesion location relative to the watershed, non-watershed and mixed brain vascular territories was annotated. The same process was performed on the T2-weighted fluid-attenuated inversion recovery images of the healthy controls using 294 regions of interest. Generalized linear mixed models for continuous outcomes were used to assess differences in size, pool size ratio and axonal volume fraction between lesions/regions of interests (in healthy controls) situated in different vascular territories. In patients, we assessed 758 T2-lesions and 356 chronic black holes (cBHs). The watershed-territories had higher relative and absolute concentrations of T2-lesions (P≤0.041) and cBHs (P≤0.036) compared to either non-watershed- or mixed-zones. T2-lesions in watershed-areas also had lower pool size ratio relative to T2-lesions in either non-watershed- or mixed-zones (P = 0.039). These results retained significance in the sub-cohort of people without vascular comorbidities and when accounting for periventricular lesions. In healthy controls, axonal volume fraction was higher only in mixed-areas regions of interest compared to non-watershed-ones (P = 0.008). No differences in pool size ratio were seen. We provide in vivo evidence that there is an association between arterial vascularisation of the brain and multiple sclerosis-induced tissue injury as early as the time of disease diagnosis. Our findings underline the importance of oxygen delivery and healthy arterial vascularisation to prevent lesion formation and foster a better outcome in multiple sclerosis.

Epidemiological, Demographic, and Clinical Characteristics of Von Willebrand Disease Patients in Zahedan City, Iran: A Descriptive Study.

Background:Von Willebrand disease (VWD) is one of the most common coagulative diseases, so identifying the effective factors in preventing this complication is essential. The study aimed to evaluate the frequency of demographic and epidemiological findings in VWD patients referred to a hospital in Zahedan, Iran. Materials and Methods: This study was performed on 76 patients with VWD referred to Hazrat Ali-Asghar Hospital in Zahedan City, Sistan, and Baluchestan province. After obtaining consent from the patients, the demographic information and clinical symptoms of the disease were recorded. All statistical analyses were performed using SPSS 22.0 software. All descriptive data were expressed as mean ±SD and percent (%) depending on the continuous and dichotomous variables. A P-value ≤0.05 was considered significant statistically. Results:The present study results showed that the highest age group of VWD patients at the time of disease diagnosis was in the age group 1-5 years (47.3%), and most patients had type III VWD (80.3%). It was also found that 67.1% of patients had a positive family history and their parents' consanguineous marriage (77.6%). The most common complaints were epistaxis (88.15%), cutaneous bleeding (78.94%), and oral cavity bleeding (61.84%), respectively. Conclusion: Due to the high prevalence of VWD in consanguineous marriages and an increase in adverse complications and symptoms in VWD patients, proper diagnosis and screening at an early age, especially in people with family history, is essential. Efforts are needed to develop national registries and widely provide the required and available basic services for diagnosis and treatment.

Prognostic difference between surgery and external radiation in patients with stage I liver cancer based on competitive risk model and conditional survival rate.

This study aimed to assess the difference in prognosis of patients with early-stage liver cancer after surgery or external radiation. Between 2010 and 2015, 2155 patients with AJCC 7th stage I liver cancer were enrolled in the SEER database. Among these, 1972 patients had undergone surgery and 183 had undergone external beam radiation. The main research endpoints were overall survival (OS) and disease-specific survival (DSS). The competitive risk model was used to calculate the risk ratio of liver cancer-specific deaths when there was a competitive risk. Propensity Score Matching (PSM) method using a 1:1 ratio was used to match confounders such as sex, age, and treatment method. Conditional survival was dynamically assessed for patient survival after surgery or external radiation. Multivariate analysis of the competitive risk model showed that age, disease diagnosis time, grade, and treatment [surgery and external beam radiation therapy (EBRT)] were independent prognostic factors for patients with hepatocellular carcinoma. Surgery had a higher survival improvement rate than that of EBRT. As the survival of patients with liver cancer increased, the survival curve of surgery declined more slowly than that of radiotherapy patients and stabilized around 3 years after surgery. The survival curve of radiotherapy patients significantly dropped within 4 years and then stabilized. Surgery was better than EBRT for patients with stage I liver cancer. Close follow-up was required for 3 years after surgery or 4 years after external radiation. This study can help clinicians make better informed clinical decisions.

Adjuvant therapy strategies for breast cancer based on the efficacy of neoadjuvant therapy

With the advent of the precision cancer therapy era, neoadjuvant therapy has become the standard therapy for certain types of breast cancer. Neoadjuvant therapy is a fundamental treatment plan implemented at the time of disease diagnosis, and its efficacy can guide the formulation of subsequent adjuvant therapy strategies. Building on the efficacy of neoadjuvant therapy and medication regimens, in conjunction with evidence-based medicine and healthcare policy, developing adjuvant therapy strategies for breast cancer following neoadjuvant therapy has the benefit of providing more precise treatment options for patients.

Rituximab as an effective add-on maintenance therapy for disease activities in childhood-onset systemic lupus erythematosus

ObjectivesSystemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that can result in high morbidity if not treated. This retrospective study aimed to evaluate the outcomes of rituximab treatment...

Quality of life of type 2 diabetes outpatients and the associated factors: A cross-sectional study at Ha Dong General Hospital in 2020

Objectives: This study aimed to describe the quality of life (QOL) of type 2 diabetes outpatients receiving treatment and the associated factors at Ha Dong General Hospital in 2020. Methods: A cross-sectional descriptive study was conducted on 327 type 2 diabetes outpatients treated at Ha Dong General Hospital in 2020 by using the Asian Diabetic Quality of Life (Asian DQOL) questionnaire into Vietnamese. Results: The mean score of overall QOL of type 2 diabetes outpatients is 68.5 ± 9.9 points. 83.2% of outpatients have good overall QOL; there were no outpatients with poor QOL. Married patients have a higher quality of life than other groups; the lowest is in the divorced or widowed group. The family economy at the non-poor level has higher quality than the poor and near-poor groups. Female patients had a higher QOL than male patients. Patients with a disease detection time of 5–10 years had the highest QOL. The group of patients with an overweight BMI had higher quality than other patients The group of patients who did not receive insulin had a higher QOL than the patients who received insulin. Patients without comorbidities had a higher QOL than the group with comorbidities. (p<0,05) Conclusions: Research results show that the majority of people with type 2 diabetes at Ha Dong General Hospital have a good QOL. Marital status, family economic status, gender, time of disease diagnosis, BMI, treatment methods, and comorbidities are factors related to patients' QOL. Key words: Quality of life, diabetes, hospital, Ha Dong

EEG Epileptic Data Classification Using the Schrodinger Operator's Spectrum.

Epilepsy is a common brain disorder characterized by recurrent, unprovoked seizures which affects over 65 million people. Visual inspection of Electroencephalograms (EEG) is common for diagnosis; however, it requires time and expertise. Therefore, an accurate computer-aided epileptic seizure diagnosis system would be valuable. A new research tendency when tackling epileptic seizure detection tends towards minimizing human manual intervention by designing frameworks with autonomous feature engineering. In this optic, this paper proposes a new approach for EEG epileptic data classification. Features derived from the Semi-Classical Signal Analysis (SCSA) method, a quantum-inspired signal processing method well-suited for the characterization of pulse-shaped physiological signals, are proposed. In addition nonlinear dynamical features that proved efficient in characterizing nonlinear dynamics of neural activity have been extracted. Moreover, hyperparameters' optimization, correlation analysis and feature selection have been performed. The selected features are fed into five different machine learning classifiers. The performance of the proposed approach has been analyzed using Bonn university database. The results show that all classifiers yield a performance accuracy of 93% and above.Clinical relevance- The paper contributes to the design of methods and algorithms to build reliable software solutions to assist medical experts and reduce epilepsy disease's diagnosis time and errors.

Relationships Between Systemic Inflammatory Markers and 18F-FDG PET/CT Imaging and Clinical Findings in Pulmonary Sarcoidosis.

Background and aim Sarcoidosis is a multisystem inflammatory disease of unknown aetiology. This study aimed to evaluate the relationship between systemic inflammatory parameters, the systemic immune-inflammation index (SII) and the lymphocyte-to-monocyte ratio (LMR), and disease stage, clinical findings, and 18F-fluoro-2-deoxy-D-glucose (18F-FDG) tomography/computed tomography (PET/CT) uptake. Materials and methods Our study included 73 patients. The general characteristics, radiological features, spirometric tests, PET/CT findings, and laboratory parameters of the patients were recorded. Results Relapse and parenchymal fibrosis were not associated with metabolic parameters, such as LMR and SII. Serum angiotensin-converting enzyme (ACE) levels were lower in the relapsed group than in the non-relapse group. However, the patients' PET/CT images indicated that 18F-FDG parenchym maximum standard uptake value (SUV max), lymph node SUV max, lymph node short axis dimension, SII, and LMR were similar between all patients, relapsed or not. Conclusion Although found to be significant in other inflammatory diseases, we found that SII and LMR alone did not indicate disease prognosis in sarcoidosis due to the small number of patients and the lack of homogeneity between the groups in our study. The usefulness of these markers for clinical use should be investigated by studies that include those with extrapulmonary sarcoidosis, and that calculate these markers at the time of disease diagnosis and during the post-treatment period.

Cross center single-cell RNA sequencing study of the immune microenvironment in rapid progressing multiple myeloma

Despite advancements in understanding the pathophysiology of Multiple Myeloma (MM), the cause of rapid progressing disease in a subset of patients is still unclear. MM’s progression is facilitated by complex interactions with the surrounding bone marrow (BM) cells, forming a microenvironment that supports tumor growth and drug resistance. Understanding the immune microenvironment is key to identifying factors that promote rapid progression of MM. To accomplish this, we performed a multi-center single-cell RNA sequencing (scRNA-seq) study on 102,207 cells from 48 CD138- BM samples collected at the time of disease diagnosis from 18 patients with either rapid progressing (progression-free survival (PFS) < 18 months) or non-progressing (PFS > 4 years) disease. Comparative analysis of data from three centers demonstrated similar transcriptome profiles and cell type distributions, indicating subtle technical variation in scRNA-seq, opening avenues for an expanded multicenter trial. Rapid progressors depicted significantly higher enrichment of GZMK+ and TIGIT+ exhausted CD8+ T-cells (P = 0.022) along with decreased expression of cytolytic markers (PRF1, GZMB, GNLY). We also observed a significantly higher enrichment of M2 tolerogenic macrophages in rapid progressors and activation of pro-proliferative signaling pathways, such as BAFF, CCL, and IL16. On the other hand, non-progressive patients depicted higher enrichment for immature B Cells (i.e., Pre/Pro B cells), with elevated expression for markers of B cell development (IGLL1, SOX4, DNTT). This multi-center study identifies the enrichment of various pro-tumorigenic cell populations and pathways in those with rapid progressing disease and further validates the robustness of scRNA-seq data generated at different study centers.

Secondary Infertility: A Neglected Aspect of Buerger's Disease.

During the gathering of demographic data for the biobank on Buerger's Disease (BD), we found that, after the clinical manifestation of BD, the patients usually became infertile, and the age of their last child was compatible with the time of disease diagnosis. The aim of this study was to evaluate the underlying cause of secondary infertility in BD patients. Anti-sperm antibodies (ASA), testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in the sera of 39 male BD patients were measured and compared with 39 age-matched Caucasian male controls. Six patients declared that they suffered from impotency. The ASA level was positive in 25.6% of the patients and 2.4% of the controls (p= 0.003, CC= 6.96). The mean levels of testosterone in the patients and controls were 393.12±32.9 ng/dl and 354.37±30.9 ng/dl, respectively. The mean levels of LH in the patients and controls were 0.88±0.12 mIU/r and 0.85±0.1 mIU/r, respectively. The mean levels of FSH in the patients and controls were 4.1± 0.35 mIU/r and 3.56±0.33 mIU/r, respectively. No significant difference in the serum levels of testosterone, LH, or FSH was found between the patients and controls (p> 0.05). The spermograms of three ASA-negative patients demonstrated impaired sperm motility. Anti-sperm antibodies, disturbed genital circulation, autonomic dysfunction and sperm motility may be responsible for secondary infertility in Buerger's Disease.

Decreased cognitive function is associated with preceding severe hypoglycemia and impaired blood glucose control in the elderly individuals with type 1 diabetes.

This investigation aimed to clarify the relationship between cognitive function and blood glucose control in the elderly individuals with type 1 diabetes. In total, 45 patients with type 1 diabetes, age 74.9 ± 6.7years, and HbA1c levels of 7.9 ± 0.9% were studied. Severe hypoglycemia occurred in 33% of patients, and the number of severe hypoglycemia episodes was 0.6 ± 1.2 in the past 5years before the time of the cognitive function tests. We analyzed clinical data and dementia scores on the Revised Hasegawa's Dementia Scale (HDS-R), Mini-Mental State Examination (MMSE), and Dementia Assessment Sheet for Community-based Integrated Care System, and 21 items (DASC-21). There was a significant correlation between HbA1c and HDS-R, MMSE, respectively. There was a significant correlation between the number of severe hypoglycemic episodes and HDS-R, MMSE, and DASC-21, respectively. When the group with experience of severe hypoglycemia was compared to the control group, HDS-R, MMSE, and DASC-21 were meaningfully different after adjusting for age modeling analysis of covariance. In elderly individuals with type 1 diabetes, our results suggest that high HbA1c for the past 5years from the cognitive function test and a history of severe hypoglycemic episodes from the time of disease diagnosis are related to decreased cognitive function.

Platelet to white blood cell ratio was an independent prognostic predictor in acute myeloid leukemia

ABSTRACT Background Recently, platelet to white blood cell ratio (PWR) was reported as an independent prognostic predictor in acute promyelocytic leukemia. Acute myeloid leukemia (AML) often presents with abnormal platelet counts and white blood cell counts (WBC) at disease diagnosis. However, the clinical impact of PWR on cytogenetically normal AML (CN-AML) is still unclear. Therefore, we evaluate its prognostic impact on CN-AML patients. Methods We recorded the clinical information at the time of disease diagnosis, and calculated the ratio of platelet counts to WBC in 338 patients with CN-AML. To assess the prognostic value of PWR, we divided patients into low, intermediate and high group based on the values of PWR. The independent prognostic value of PWR was investigated in the context of the well-established predictors including white blood cell counts, age, and genes of NPM1, FLT3-ITD, CEBPA, and DNMT3A mutations. Receiver operating characteristic (ROC) curve was used to assess the performance of its prognostic prediction. Results Higher PWR have the higher levels of platelet counts, but lower levels of white blood cell counts, percentage of bone marrow blasts, FLT3-ITD and NPM1 mutations. The performance of survival prediction was comparable between PWR alone and combined molecular biomarkers. Moreover, PWR had the additional prognostic information to the molecular biomarkers. Finally, PWR was associated with favorable overall survival and event free survival in CN-AML patients independent of genetic subtypes and clinical parameters. Conclusion We found PWR was an independent prognostic predictor in CN-AML.

Demographic, clinical, laboratory data, prognostic, and treatment features of patients with antisynthetase syndrome: An international, two-center cohort study.

To compare clinical, demographic, laboratory data, prognostic and treatment characteristics of patients with antisynthetase syndrome (ASSD) treated in two different centers of India and Brazil. This international, two-center, retro-prospective cohort study which was conducted at two tertiary rheumatology centers (one in Brazil and one in India) between January 2000 to January 2020 included a total of 115 patients with ASSD (21 males, 94 females; mean age; at disease diagnosis at 40.3; range, 18 to 80 years). Demographic, clinical and laboratory data of the patients were recorded. Clinical involvement was evaluated. Of the patients, 81 were Brazilians and 34 were of Indian origin. The Indian group exhibited a greater delay in diagnosis after the onset of symptoms compared to Brazilian patients (12 vs. 6 months, respectively; p=0.026). Brazilian patients exhibited a significantly higher prevalence of joint and lung involvement, mechanic's hands, and Raynaud's phenomenon. Anti-Jo-1 was the most common autoantibodies in both groups. Systemic arterial hypertension, followed by diabetes mellitus were the most prevalent comorbidities. Concerning previously used drugs, the Indian patients had a larger group of patients treated with antimalarials, whereas the Brazilian group used more azathioprine and intravenous immunoglobulin. A higher proportion of Indian patients was treated with one immunosuppressive drug (70.6%), while the Brazilian group were often treated using two immunosuppressive drugs (33%). Comparison between the severity and prognosis showed that Brazilian group had a higher number of relapses, and during follow-up, the global mortality rates were similar in both groups (6.2% for Brazilian vs. 8.8% for Indian). Brazilian and Indian patients with ASSD have comparable epidemiological characteristics such as age at the time of disease diagnosis, and sex distribution, and autoantibodies. Diagnostic delay is seen in Indian patients, and Brazilians exhibit a higher prevalence of joint and lung involvement, mechanic's hands, Raynaud's phenomenon with a higher number of relapses, although the mortality rate seems to be similar in both groups.

Poor glycemic control and associated factors in diabetic people attending a reference outpatient clinic in Mato Grosso, Brazil.

Objective:To identify the proportion of poor of glycemic control and associated factors among people with type 2 diabetes attending a regional reference outpatient clinic in Mato Grosso (Brazil).Methods:This is a cross-sectional quantitative study based on data from medical records of 338 people with type 2 diabetes who attend a state reference outpatient clinic in Mato Grosso (Brazil). Information on glycemic control, sociodemographic factors, lifestyle and clinical conditions was collected.Results:The prevalence of elevated glycated hemoglobin was 47.34%. In the Poisson multiple regression model analysis with robust variance, poor glycemic control was significantly associated (p<0.05) with the following factors: insulin use (Prevalence Ratio -PR = 2.03), fasting glucose ≤70 and ≥100 mg/dL (PR = 2.0), postprandial glucose ≥180 mg/dL (PR = 1.76), no physical activity (PR = 1.62), the interaction between age group ≤59 years and the time of disease diagnosis >10 years (PR = 1.58), and presence of arterial hypertension (PR = 0.79).Conclusion:Most users of the reference outpatient clinic with type 2 diabetes had poor glycemic control associated with risk factors that alter glycated hemoglobin and negatively affect the achievement of established glycemic levels.

Neutrophil extracellular traps in giant cell arteritis biopsies: presentation, localization and co-expression with inflammatory cytokines.

To explore the presence of neutrophil extracellular traps (NETs) in inflamed temporal artery biopsies (TABs) of patients with GCA. Ten patients with GCA [five with limited and five with associated generalized vascular involvement, as defined by 18F-fluorodeoxyglucose PET with CT (PET/CT)] and eight with PMR were studied. The presence, location, quantitation and decoration of NETs with IL-6, IL-1β and IL-17A were assessed in TABs at the time of disease diagnosis by tissue immunofluorescence and confocal microscopy. Paired serum levels of IL-6 and IL-17A were also evaluated in all patients. All temporal artery biopsies from GCA, but not PMR, patients had NETs located mainly in the adventitia, adjacent to the vasa vasorum. NETs decorated with IL-6 were present in 8/10 TABs of GCA patients, of whom 5 were PET/CT(+) and 3 PET/CT(-) patients. IL-17A(+) NETs were observed in all GCA patients. IL-1β(+) NETs were not detected in any GCA patient. No relation was found between serum IL-6 and IL-17A levels and NETs containing IL-6 and/or IL-17A. NETs bearing pro-inflammatory cytokines are present in inflamed GCA-TABs. Future studies with a larger number of patients from different centres will show whether the findings regarding neutrophils/NETs in the TAB are consistent and disclose their clinical impact.

Association between Elevated TGA-IgA Titers and Older Age at Diagnosis with Absence of HBV Seroconversion in Celiac Children.

Patients with celiac disease can have a low rate of protective hepatitis B (HBV) antibody titers after vaccination. We aimed to evaluate the HBV seroconversion in celiac disease (CD) children at the time of diagnosis as well as to identify the presence of possible predictive factors. Celiac disease children were prospectively enrolled and tested for antibodies against the S protein of HBV (HBsAg) at time of diagnosis between January 2009 and February 2020. Based on the serologic response to the vaccine, “responders” and “non-responders” were identified. Statistical analysis has been performed through R statistical software (3.5.1 version, R core Team) Of 96 CD children evaluated, 41.7% (n = 40) showed non-protective or absent antibody titers against HBV. Elevated IgA-antibodies against transglutaminase 2 (TGA-IgA) values and older age at diagnosis were associated with an absent seroconversion to HBV vaccine, while presenting symptoms were not significant. An elevated prevalence of absent seroconversion to HBV vaccine exists in this cohort of CD patients at the time of disease diagnosis. Elevated TGA-IgA titers and older age at diagnosis seem to negatively predict seroconversion. Further studies are needed to identify the real profile of “non-responders”, aiming to organize surveillance and eventual revaccination strategy.

S0823 Disease Disclosure Preferences and Stigma Among Patients With Inflammatory Bowel Disease

INTRODUCTION: Perceived stigma reflects people's perception of discrimination directed at them or others and is associated with poorer quality of life, medication compliance, self-esteem, and worsened depression. This study aims to 1) examine the habits and preferences of disease disclosure among those with IBD and 2) investigate the predictors of perceived and internalized disease disclosure stigma. METHODS: We administered a survey to 101 patients with an established diagnosis of IBD at Boston Medical Center, Boston, MA and at the Mayo Clinic, Jacksonville, FL. We assessed participant demographics, disease severity and duration, reasons for and against disease disclosure, and preferences for IBD resources at time of disease diagnosis. We also assessed participant disease disclosure stigma, work absenteeism, medication compliance using the MARS-5 scale, and anxiety using the GAD-7 scale. We used descriptive statistics to characterize participants and multivariate linear regression to assess predictors of perceived and internalized disease disclosure stigma. RESULTS: Participants were most comfortable disclosing their IBD status to parents and significant other, and least comfortable disclosing to colleagues, acquaintances and strangers (Figure 1). All participants agreed that various disclosure resources would be valuable to patients newly diagnosed with IBD. The most frequently cited resources include: information regarding the nature and disease course of IBD, Q&A sessions led by IBD specialists and patients, and information about online support groups. In multivariate analyses, prior "bad experience" with disease disclosure was associated with higher perceived disease disclosure stigma (P = 0.005). Higher education (college or post-graduate) was associated with lower internalized disease disclosure stigma. CONCLUSION: Navigating disease disclosure is an important aspect to managing an diagnosis of IBD. Our study highlights the importance of providing various disclosure resources to newly diagnosed patients who may struggle with their IBD. Moreover, our findings show that a prior "bad experience" with IBD disclosure negatively influenced patients' perceptions of stigma, further reinforcing the notion that patients with IBD may benefit from disclosure resources. Future research should build on our findings by empirically testing the impact of various disclosure resources on patient disclosure behavior and perception of disease-related stigma.Table 1Figure 1

Exploring celiac disease candidate pathways by global gene expression profiling and gene network cluster analysis

Celiac disease (CeD) is a gastrointestinal autoimmune disorder, whose specific molecular basis is not yet fully interpreted. Therefore, in this study, we compared the global gene expression profile of duodenum tissues from CeD patients, both at the time of disease diagnosis and after two years of the gluten-free diet. A series of advanced systems biology approaches like differential gene expression, protein–protein interactions, gene network-cluster analysis were deployed to annotate the candidate pathways relevant to CeD pathogenesis. The duodenum tissues from CeD patients revealed the differential expression of 106 up- and 193 down-regulated genes. The pathway enrichment of differentially expressed genes (DEGs) highlights the involvement of biological pathways related to loss of cell division regulation (cell cycle, p53 signalling pathway), immune system processes (NOD-like receptor signalling pathway, Th1, and Th2 cell differentiation, IL-17 signalling pathway) and impaired metabolism and absorption (mineral and vitamin absorptions and drug metabolism) in celiac disease. The molecular dysfunctions of these 3 biological events tend to increase the number of intraepithelial lymphocytes (IELs) and villous atrophy of the duodenal mucosa promoting the development of CeD. For the first time, this study highlights the involvement of aberrant cell division, immune system, absorption, and metabolism pathways in CeD pathophysiology and presents potential novel therapeutic opportunities.

The timing of geographic power.

In many studies on the spatial risk of disease, investigators use geographic locations at the time of disease diagnosis in spatial models to search for individual areas of elevated risk. However, these studies often fail to find a significant spatial signal. This may be due to the misspecification of the timing and location of pertinent exposures. Environmental exposures related to cancer risk vary over space and time, and many cancers have long latencies. When these factors are considered in conjunction with a mobile population, it is likely that the spatial signal related to relevant historic environmental exposures is obscured. To investigate this hypothesis, we conducted simulation studies to characterize the effect of residential mobility on the ability of generalized additive models to detect areas of significantly elevated historic environmental exposure. We generated data based on the residential histories of participants in the National Cancer Institute Surveillance, Epidemiology, and End Results non-Hodgkin lymphoma study, and varied the duration and intensity of the environmental exposure. Results showed that the probability of detection, mean spatial sensitivity, and mean spatial specificity of models decreased steadily as the time since relevant exposure increased. This suggests that for diseases with long latencies, spatial areas of high risk due to high-intensity exposure of relatively short duration will be difficult to detect over time when using residential locations at the time of diagnosis in mobile study populations.

"Five-Early" Model: The Magic Weapon against COVID-19.

Background:COVID-19(2019 novel coronavirus disease)has brought tremendous pressure to the prevention and control of the national epidemic due to its concealed onset, strong infectivity and fast transmission speed.Methods:In this retrospective study, 226 patients diagnosed with 2019 novel coronavirus pneumonia (NCP) in the Chongqing University Three Gorges Hospital were included. The patients’ clinical data, including general information, initial symptoms at the onset, time of disease diagnosis, time to treatment in hospital, time of nucleic acid conversion to negative, disease classification, total time of hospitalization were collected. The clinical data of the mild and severe patients were compared.Results:Fever, cough, sore throat, poor appetite andfatigue were the main symptoms of the diagnosed patients. The time of diagnosis was significantly shorter in the mild patients (4.96 ± 4.10 days) than severe patients (7.63 ± 9.17 days) (P=0.004). Mild patients had shorter time to treatment in hospital (6.09 ± 4.47 vs. 8.71 ± 9.04 days) and less time of nucleic acid conversion to negative (7.58 ± 2.51 vs. 11.6 ± 4.67 days) compared to the severe patients.Conclusion:The above results can be used as a quantitative basis for the “five-early”(early detection, early screening, early diagnosis, early isolation treatment, and early recovery) model. The government, the masses, and the hospitals’ joint prevention and optimization of the “five-early” model will provide important scientific reference for further prevention and control of the epidemics.