Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Method for Quantifying Intestinal Inflammatory Burden in Inflammatory Bowel Disease Using Register Data

Background The Swedish Quality Register for Inflammatory Bowel Disease (SWIBREG) contains clinical data for the study of inflammatory bowel disease (IBD). The Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort was recently established for the study of gastrointestinal histopathology. We aimed to develop and validate a histology score from ESPRESSO using clinical information from SWIBREG, and secondarily, to evaluate the association of the score on IBD-related hospitalization. Methods In a nationwide, population-based cohort study of patients with IBD during 1969–2017, we linked endoscopic inflammation in SWIBREG with histologic inflammation in ESPRESSO. We established a clinically interpretable model for predicting the endoscopic score from histology using scalable Bayesian rule lists to define a SNOMED-based histology score applicable to the ESPRESSO cohort. We also assessed the impact of baseline endoscopic and histology scores on time to IBD-related hospitalization. Results We identified 5225 individuals with IBD comprising 11,051 endoscopic assessments in SWIBREG linked to a histopathology record in ESPRESSO. We created predictive models to calculate a SNOMED-based histology score which predicted the endoscopic score. Split-sample validated areas under the ROC curves for the score predicting a non-zero endoscopic score were 0.80 (0.78–0.81) in UC, 0.70 (0.68–0.72) in CD, and 0.76 (0.73–0.78) in IBD-U. In a subset of 2741 individuals with an initial IBD diagnosis and a corresponding record in ESPRESSO with an endoscopic assessment in SWIBREG, the baseline endoscopic and histology scores were associated with time to IBD-related hospitalization (endoscopy log-rank UC p<0.001, CD p=0.020, IBD-U p<0.001; histology log-rank UC p=0.018, CD p=0.960, IBD-U p=0.034). Conclusion Histopathology data in ESPRESSO accurately predict endoscopic scores in SWIBREG. Baseline endoscopic and histologic scores were associated with time to IBD-related hospitalization, particularly in UC. The SNOMED-based histology score can be used as a measure of disease activity in future register-based IBD studies.
The Bayesian Spatial Bradley–Terry model: Urban deprivation modelling in Tanzania

Identifying the most deprived regions of any country or city is key if policy makers are to design successful interventions. However, locating areas with the greatest need is often surprisingly challenging in developing countries. Due to the logistical challenges of traditional household surveying, official statistics can be slow to be updated; estimates that exist can be coarse, a consequence of prohibitive costs and poor infrastructures; and mass urbanization can render manually surveyed figures rapidly out‐of‐date. Comparative judgement models, such as the Bradley–Terry model, offer a promising solution. Leveraging local knowledge, elicited via comparisons of different areas' affluence, such models can both simplify logistics and circumvent biases inherent to household surveys. Yet widespread adoption remains limited, due to the large amount of data existing approaches still require. We address this via development of a novel Bayesian Spatial Bradley–Terry model, which substantially decreases the number of comparisons required for effective inference. This model integrates a network representation of the city or country, along with assumptions of spatial smoothness that allow deprivation in one area to be informed by neighbouring areas. We demonstrate the practical effectiveness of this method, through a novel comparative judgement data set collected in Dar es Salaam, Tanzania.
Single-cell analysis reveals immune modulation and metabolic switch in tumor-draining lymph nodes

ABSTRACT Lymph-node metastasis is a prognosis factor for poor clinical outcome of breast cancer patients. Currently, how breast cancer cells establish pre-metastatic niche in the tumor-draining lymph nodes (TDLNs) is still unclear. To address this question, we isolated heterogeneous cells including immune and stromal cells from naive lymph nodes (LNs) of the FVB/NJ mice and TDLNs of the MMTV-PyMT mice. Single-cell RNA sequencing was performed to investigate the transcriptome of the cells and various bioinformatics analyses were used to identify the altered pathways. Our results revealed several significant changes between naïve LNs and TDLNs. First, according to immunologic signature and pathway analysis, CD4+ and CD8 + T cells showed upregulated angiogenesis pathway genes and higher regulatory T (Treg)-associated genes while they demonstrated downregulation of interferon response and inflammatory response gene signatures, concurrently suggesting an immunosuppressive microenvironment in the TDLNs. Second, profiling of B cells showed down-regulation of marginal zone B lymphocytes in the TDLNs, which was validated by flow cytometric analysis. Third, we found the enhancement of oxidative phosphorylation pathway in the fibroblastic reticular cells (FRCs) of the MMTV-PyMT mice and the elevation of related genes including Prdx3, Ndufa4 and Uqcrb, suggesting massive ATP consumption and TCA cycle metabolism in the FRCs. Collectively, our results reveal the reprogramming of TDLNs during breast cancer progression at single-cell level in a spontaneous breast cancer model and suggest the changes in immune modulation and metabolic switch are key alterations in the preparation of pre-metastatic niche by breast cancer cells.
2'-Hydroxychalcones and their Cyclized Derivatives as Cathepsin L Inhibitors

Elevated levels of various cathepsins in cancer and inflammation necessitate exploring their potential inhibitors. Cathepsin L has been a potential drug target in these diseased conditions. In search for novel chemotherapeutic agents with better efficacy, potential inhibitors of target molecules need to be identified. In the present study, we have assayed the inhibitory potency of three structurally related series of flavanoids i.e., 2’-hydroxychalcones, flavanones and flavones against cathepsin L.
JAK-STAT Domain Enhanced MUC1-CAR-T Cells Induced Esophageal Cancer Elimination

Purpose Chimeric antigen receptor (CAR)-T cells have shown to play a vital role in anti-tumor functions in hematological malignancies, but have poor efficacy in solid tumors. To improve the activation and proliferation of CAR-T cell in solid tumors, we constructed an enhanced CAR-T cells to increase the survival of esophageal cancer. Materials and Methods To construct enhanced CAR-T cells, we chose MUC1 as the target of CAR-T cells. Long-term co-culture of target cells and effector cells was applied to verify the antitumor activity of these enhanced MUC1-CAR-T cells in vitro. Moreover, a mouse xenograft model was established to investigate the effects of enhanced MUC1-CAR-T cells on tumor elimination in vivo. Results In vitro studies showed that enhanced MUC1-CAR-T cells have long-lasting tumor killing and proliferative capabilities. Moreover, animal experiments verified that enhanced MUC1-CAR-T cells had significant antitumor function and a prolonged half-life by subcutaneous transplantation models of esophageal cancer and PDX models of esophageal cancer, in vivo. Conclusion These results indicated that enhanced MUC1-CAR-T cells have a significant cytotoxic effect on esophageal cancer, and may likely to provide a novel strategy for the treatment of esophageal cancer.
U-Shaped Association of High-Density Lipoprotein Cholesterol with All-Cause and Cardiovascular Mortality in Hypertensive Population

Purpose Whether the paradox of high-density lipoprotein cholesterol (HDL-C) and elevated mortality risk extends to hypertensive patients is unclear. We aimed to investigate the association between HDL-C and all-cause and cardiovascular disease mortality in adults with hypertension. Methods In the National Health and Nutrition Examination Surveys, 11,497 hypertensive participants aged ≥18years old and examined at baseline between 1999 and 2014 were followed up until December 2015. We categorized the HDL-C concentration as ≤30, 31–40, 41–50, 51–60 (reference), 61–70, >70 mg/dL and examined their associations with all-cause and cardiovascular mortality, respectively. Multivariate Cox regression was used to calculated hazard ratio (HR) and 95% confidence interval (CI) for mortality risk. Results During follow-up (median: 9.2 ± 3.8 years), 3012 deaths and 713 cardiovascular deaths were observed. In the restrictive cubic curves, associations of HDL-C levels and all-cause and cardiovascular mortality were detected to be U-shaped. After multivariable adjustment, HRs for all-cause mortality were for the lowest HDL-C concentration (≤30 mg/dL) 1.29 (95% CI, 1.07–1.56) and the highest (>70 mg/dL) 1.20 (1.06–1.37), comparing with the reference group. For cardiovascular mortality, HRs were 1.31 (0.83–1.48) and 1.09 (0.83–1.43), respectively. Similar results were obtained in subgroups stratified by age, gender, race, and taking lipid-lowering drugs. The lowest all-cause mortality risk was observed at HDL-C 66 mg/dL (concentration) and 51–60 mg/dL (range). Conclusion Both lower and higher HDL-C concentration appeared to be associated with higher mortality in hypertensive population. Further investigation is warranted to clarify the underlying mechanisms.
Conjunctival Melanoma: Update on Genetics, Epigenetics and Targeted Molecular and Immune-Based Therapies

Purpose To present the molecular mechanisms involved in the pathogenesis of conjunctival melanoma (CM) and review the existing literature on targeted molecular inhibitors as well as immune checkpoint inhibitors for the management of locally advanced and metastatic disease. Methods A comprehensive review of the literature was performed using the keywords “conjunctival melanoma”, “immune checkpoint inhibitors”, “BRAF inhibitors”, “MEK inhibitors”, “CTLA4 inhibitors”, “PD1 inhibitors”, “c-KIT mutations”, “BRAF mutations”, “NRAS mutations”, “dabrafenib”, “trametinib”, “vemurafenib”, “ipilimumab”, “pembrolizumab”, and “nivolumab”. A total of 250 articles were reviewed and 120 were included in this report. Results Mutations of mediators in the MAP kinase pathway, such as RAS, BRAF, MEK and ERK, and mutations of the PI3K/AKT/mTOR pathway play a major role in the pathogenesis of conjunctival melanoma. In addition, alterations of c-KIT, NF1, TERT, chemokine receptors as well as chromosomal copy number alterations and micro RNAs are thought to have a causative association with CM development. Targeted molecular inhibitors, such as BRAF and MEK inhibitors, are currently being implemented in the therapy of BRAF-mutated CM. Furthermore, immune checkpoint PD-1 and CTLA4 inhibitors with favorable clinical outcomes in the treatment of cutaneous melanoma have increased recurrence-free survival and reduced metastatic spread in CM cases. Conclusion The complex molecular mechanisms that contribute to the development of CM can be targeted both by molecular inhibitors of oncogenic pathways as well as immune checkpoint inhibitors in order to halt progression of the disease and increase survival.
Expression and Clinical Prognostic Value of Platelet NLRP3 in Acute Coronary Syndrome

Purpose Little is known about the relationship between the level of platelet NOD-like receptor protein 3 (NLRP3) and the severity of acute coronary syndrome (ACS) or the prognostic value of platelet NLRP3 for percutaneous coronary intervention (PCI). Methods Platelets collected from 25 healthy subjects, 23 patients with stable angina pectoris (SAP), and 72 patients with ACS were analyzed by Western blotting and real-time fluorescence quantitative PCR (qPCR). A total of 152 patients with ACS who had undergone PCI were included in this study to evaluate the prognostic value of platelet NLRP3. Results The levels of platelet NLRP3 in both the healthy and SAP groups were clearly lower than in the ACS group (P<0.001). According to the Pearson correlation analysis, the expression of platelet NLRP3 was closely related to the mean platelet volume (MPV), left ventricular ejection fraction (LVEF), the Gensini score, and the Global Registry of Acute Coronary Events (GRACE) score (all P<0.001). Multivariate logistic regression analysis identified NLRP3 as an independent risk factor for adverse cardiovascular events (ACEs) after PCI (P=0.004). The proportion of patients with high NLPR3 expression (the NLRP3-high group) remaining free of adverse events for 3 years was remarkably lower than that in patients with low NLPR3 expression (the NLRP3-low group; P=0.024). The NLRP3-high group had a significantly higher proportion of patients with interleukin-1β–expressing (20.4%±6.1%) platelets than the NLRP3-low group (10.7%±3.5%, P<0.001). Moreover, the NLRP3-high group exhibited higher platelet activity, as indicated by increased PAC-1 binding and CD62P expression, compared with the NLRP3-low group (P<0.001). Conclusion These results indicated that platelet NLRP3 was a novel potential prognostic factor for patients with ACS that underwent PCI.
Perceptions and usage of selected fermented foods for feeding children aged 13-60 months in Tshwane, Gauteng Province

Introduction fermented indigenous foods are known to confer health and nutritional benefits to young children. However, perception and usage of these foods is not well understood. This study aimed to determine the perceptions and usage of fermented foods, by child caregivers, for children feeding in Gauteng Province, South Africa. Methods a standard questionnaire was used to obtain data from child caregivers on the perceptions and usage of fermented foods to feed young children in Tshwane metro. Results a total of 1248 child caregivers completed the questionnaires. Their age ranged from 15-65 years, 71.7% being single, with majority (74%) having attained secondary school education and unemployed (65%). Over 60% of children were fed sour milk (maas), sour porridge and yoghurt at a frequency of 1-3 times a week, with the feeding starting at the age of 6-12 months. Majority (59-74%) had positive perceptions on benefits of feeding children with fermented foods. Conclusion there is a high acceptability of fermented foods for feeding children in this community. Further promotion of these foods may improve the frequency of their usage.
Implication of Microsatellite Instability in Chinese Cohort of Human Cancers

Background Microsatellite instability (MSI) has been a hot topic in cancer research. Determining MSI status greatly aids tumor prognosis and treatment plans. However, MSI data for Asian cancer patients with prognostic information are scarce. Here, our aim was to clarify MSI status and its prognostic value in a large Chinese cohort with different tumors. Patients and Methods Tissue samples from 600 Chinese cases, including 150 endometrial cancers, 150 colorectal cancers, 150 liver cancers and 150 gastric cancers, were used for IHC and MSI examinations. Two mononucleotide and three dinucleotide markers were used to analyze MSI status. Results In total,17.3% (26/150) of endometrial cancer patients showed positive MSI,10.0% (15/150) in colorectal cancer, 2.7% (4/150) in liver cancer, and 2.7% (4/150) in gastric cancer. Tumor location (P < 0.001 for colorectal cancer) and clinical stage (P =0.038 for gastric cancer) showed significant correlations with MSI status in gastrointestinal carcinogenesis. The mismatch repair (MMR) deficiency was observed in 20 colorectal cases (13.3%) and was significantly more frequent in the MSI-positive group (P < 0.001). Interestingly, the prevalence of MSI-H was mostly occurred in early-stage tumors, and none was in late stage (stage IV). Meanwhile, low clinicopathological stage had significant correlation with longer survival in multiple cancers here. Conclusion The incidence of microsatellite instability varies among different cancer types. And the prevalence of MSI-H mostly occurred early clinicopathological stage. In addition, our study provided a large Asian cohort screened by five loci PCR method and significantly increased knowledge on the prognostic significance of MSI in Asia.
Roseomonas gilardii in patient with leukemia and acute appendicitis: case report and review

Appendicitis is one of the most common abdominal conditions requiring emergency surgery. However, acute appendicitis in patients with leukemia is a rare condition. We report herein the case of an 18-year-old female with acute lymphoblastic leukemia (ALL), who was hospitalized in hematology department because of abdominal pain and fever. Ultrasound (US) of the abdomen revealed appendicitis and the patients underwent open appendectomy. The patient recovered without complications and was discharged in a good condition. The day of the operation blood and peritoneal fluid cultures were taken and Roseomonas gilardii was detected and healed empirically. The correct diagnosis of appendicitis in patients with leukemia and their management is challenging for physicians. Very rare microorganisms can be detected in these patients.
Inflammation Mediated Hepcidin-Ferroportin Pathway and Its Therapeutic Window in Breast Cancer

Abstract Experimental and clinical data strongly support that iron is an essential element which plays a big role in cancer biology. Thus, hepcidin (Hp) and ferroportin (Fpn) are molecules that regulate and maintain the metabolism of iron. A peptide hormone hepcidin limits recycled and stored iron fluxes in macrophage and hepatic hepatocyte, respectively, to the blood stream by promoting degradation of the only iron exporter, Fpn, in the target cells. Moreover, the inflammatory microenvironment of breast cancer and altered hepcidin/ferroportin pathway is intimately linked. Breast cancer exhibits an iron seeking phenotype that is accomplished by tumor-associated macrophage (TAM). Because macrophages contribute to breast cancer growth and progression, this review will discuss TAM with an emphasis on describing how TAM (M2Ф phenotypic) interacts with their surrounding microenvironment and results in dysregulated Hp/Fpn and pathologic accumulation of iron as a hallmark of its malignant condition. Moreover, the underlying stroma or tumor microenvironment releases significant inflammatory cytokines like IL-6 and bone morphogenetic proteins like BMP-2 and 6 leading in aberrant Hp/Fpn pathways in breast cancer. Inflammation is primarily associated with the high intracellular iron levels, deregulated hepcidin/ferroportin pathway, and its upstream signaling in breast cancer. Subsequently, scholars have been reported that reducing iron level and manipulating the signaling molecules involved in iron metabolism can be used as a promising strategy of tumor chemotherapy. Here, we review the key molecular aspects of iron metabolism and its regulatory mechanisms of the hepcidin/ferroportin pathways and its current therapeutic strategies in breast cancer.
Reliability and Validity of THINC-it in Evaluating Cognitive Function of Patients with Bipolar Depression

Purpose The THINC-integrated tool (THINC-it) as a brief screening tool can assesses cognitive impairment in patients with major depressive depression (MDD). Here, we aim to evaluate the reliability and validity of the THINC-it in a bipolar depression (BD-D) group in comparison with a healthy control (HC) group. Materials and Methods Both groups were matched according to age, gender, years of education, and IQ. All participants completed the THINC-it test, including Spotter, Symbol Check, Codebreaker, Trails, and the Perceived Deficits Questionnaire for Depression-5-item (PDQ-5-D). The concurrent validity and internal consistency of the THINC-it test were analyzed, and 30 healthy controls were randomly sampled to retest THINC-it to verify the reliability of the THINC-it retest. The correlation between THINC-it and Hamilton Depression Scale (HAMD-17) and Sheehan Disability Scale (SDS) was also analyzed. Results Fifty-eight patients with BD-D and 61 HCs were included for final analysis. There were significant mean difference (MD) standard errors (SE) between two groups in PDQ-5-D, Spotter and Codebreaker (all P<0.01), Trails (P=0.015). There was no significant difference in Symbol Check (MD (SE)=−0.01 (0.18), P=0.938; 95% CI=−0.38 to 0.35). The Cronbach’s α of PDQ-5-D was 0.640. The intraclass correlation coefficient (ICC) was between 0.440 and 0.757. The highest concurrent validity was PDQ-5-D (r=0.812, P<0.001). PDQ-5-D was positively correlated with HAMD-17 and SDS score (P<0.01). The objective test had no significant correlation with HAMD-17 and SDS scores (P>0.05). Conclusion This study found that THINC-it can accurately present the cognitive impairment of patients with BD-D. It can be potentially applied in assessing the cognitive function of patients with BD-D although Symbol Check may not accurately reflect the level of cognitive function. The concurrent validity and retest reliability are lower than expected, we need to further increase the sample size to study.
Surgical Site Infections and Prophylaxis Antibiotic Use in the Surgical Ward of Public Hospital in Western Ethiopia: A Hospital-Based Retrospective Cross-Sectional Study

Objective Surgical site infection (SSI) is one of the leading causes of hospital-acquired infection among hospitalized patients. It causes significant health problems and results in an extended length of hospital stay, increased cost, and increased patient morbidity and mortality. To prevent the development of SSI, surgical antibiotic prophylaxis (SAP) administration before surgery is an evidence-based practice. Therefore, this study aimed to assess the prevalence of SSIs and surgical antibiotic prophylaxis practice, and identifying the gap in practicing prophylactic surgical antibiotic use. Methods A retrospective cross-sectional study design was conducted on randomly selected 281 participants who fulfilled the inclusion criteria. Appropriateness of surgical antibiotic prophylaxis was assessed by clinical pharmacists based on the standard treatment guideline. Descriptive and multivariate logistic regression analyses were performed in SPSS version 25. Statistical significance was set at p <0.05. Results The overall prevalence of SSI was 19.6% (95% CI: 19–20.2). Majority of surgical patients (88.6%) got surgical antibiotic prophylaxis. Ceftriaxone and metronidazole (45.4%), and ceftriaxone (33.3%) were the most frequently used prophylactic antibiotics. Presence of comorbidity (AOR=9.18, 95% CI: 5.17–17.9, p<0.001), contaminated (AOR=6.01, 95% CI: 1.77–16.8, p=0.019) and dirty (AOR=7.20, 95% CI: 1.23–12.1, p=0.029) wound classes, devoid of prophylactic antibiotics (AOR=6.63, 95% CI: 0.89–19.3, p=0.006), the timing of prophylactic antibiotic administration between 1 hour and 2 hours before incision (AOR=8.2, 95% CI: 4.34–18.1, p=0.001), and 48 hours duration of surgical antimicrobial prophylaxis (AOR=7.20, 95% CI: 1.23–28.17, p=0.027) were significantly associated with the development of SSIs. Conclusion The prevalence of SSI was relatively high despite most surgical patients were given prophylactic antibiotics. The presence of comorbidity, contaminated and dirty wound classes, devoid of prophylactic antibiotics, administering prophylactic antibiotics between 1 hour and 2 hours before incision, and 48 hours duration of surgical antibiotic prophylaxis were significantly associated with SSIs.