Miracle-dz/UniFAR-FTUs huggingface dataset:
Extracellular vesicles shed by follicular lymphoma B cells promote the polarization of bone marrow stromal cell niche.

Follicular Lymphoma (FL) originates in the lymph nodes (LN) and infiltrates bone marrow (BM) early in the course of the disease. BM FL B cells are characterized by a lower cytological grade, a decreased proliferation, and a specific phenotypic and subclonal profile. Mesenchymal stromal cells (MSC) obtained from FL BM display a specific gene expression profile (GEP), including enrichment for a lymphoid-stromal cell signature, and an increased capacity to sustain FL B-cell growth. However, the mechanisms triggering the formation of the medullar FL permissive stromal niche have not been yet identified. In the current work, we demonstrated that FL B cells produced extracellular vesicles (EVs) that could be internalized by BM-MSC, making them more efficient to support FL B-cell survival and quiescence. Accordingly, EVs purified from FL BM plasma activated TGF-b dependent and independent pathways in BM-MSC, modified their GEP, triggering an upregulation of factors classically associated with hematopoietic stem cell niche, including CXCL12 or angiopoietin-1. Moreover, we provided the first characterization of BM FL B-cell GEP, allowing the definition of the landscape of molecular interactions they could engage with EV-primed BM-MSC. This work identified FL-derived EVs as putative mediators of BM stroma polarization and supported further investigation of their clinical interest for targeting the crosstalk between BM-MSC and malignant B cells.
Glucagon‐like peptide‐1 receptor agonists and sodium‐glucose cotransporter 2 inhibitors for diabetes after solid organ transplantation

Post‐transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation and a major cause of increased morbidity and mortality. Additionally, solid organ transplant patients may have pre‐existent type 2 diabetes mellitus (T2DM). While insulin is the treatment of choice for hyperglycemia in the first weeks after transplantation, there is no preferred first line agent for long‐term management of PTDM or pre‐existent T2DM. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) and sodium–glucose cotransporter 2 (SGLT2) inhibitors improve glycemic control, lower body weight, and blood pressure, are recommended after lifestyle and metformin as initial therapy for diabetic patients with cardiovascular or kidney comorbidities regarding their cardiorenal benefits. Furthermore, the mechanisms of action of GLP‐1RA may counteract some of the driving forces for PTDM, as calcineurin‐induced β cell toxicity as per preclinical data, and improve obesity. However, their use in the treatment of PTDM is currently limited by a paucity of data. Retrospective observational and small exploratory studies suggest that GLP‐1RA effectively improve glycemic control and induce weight loss in patients with PTDM without interacting with commonly used immunosuppressive agents, although randomized‐controlled clinical trials are required to confirm their safety and efficacy. In this narrative review, we evaluate the risk factors and pathogenesis of PTDM and compare the potential roles of GLP‐1RA and SGLT2 inhibitors in PTDM prevention and management as well as in pre‐existent T2DM, and providing a roadmap for evidence generation on newer antidiabetic drugs for solid organ transplantation.
hsa-miR-5580-3p inhibits oral cancer cell viability, proliferation and migration by suppressing LAMC2

The present study aimed to explore whether and how microRNA-5580-3p (miR-5580-3p) affected oral cancer (OC) cell phenotypes via regulation of laminin subunit γ2 (LAMC2). Bioinformatics analysis was used to identify miR-5580-3p/LAMC2, a novel interactome that, to the best of our knowledge, has not been studied previously in OC. In the present study, the expression levels of miR-5580-3p and LAMC2 were detected by reverse transcription-quantitative PCR, while the protein expression levels of LAMC2 were identified using western blotting. To determine the effects of miR-5580-3p and LAMC2 in OC, a number of experiments, including Cell Counting Kit-8, 5-bromo-2′-deoxyuridine cell proliferation and wound healing migration assays, were performed using OC SCC-4 and Cal-27 cell lines. Additionally, luciferase reporter assays were employed to examine the interaction between miR-5580-3p and LAMC2 mRNA. The results demonstrated that miR-5580-3p expression was downregulated, while LAMC2 expression was upregulated in OC tissues and cell lines. In addition to the observation that miR-5580-3p promoted the malignant phenotypes of OC, it was also revealed that miR-5580-3p inhibited OC cell viability, proliferation and migration by suppressing LAMC2. Therefore, the present study suggested that miR-5580-3p and LAMC2 may be potential biomarkers and therapeutic targets for OC diagnosis and therapies in the future.
Tumor attenuation and quantitative analysis of perfusion parameters derived from tri-phasic CT scans in hepatocellular carcinoma

Abstract The aim of the current study was to explore the value of tumor attenuation and quantitative analysis of perfusion parameters obtained from traditional tri-phasic CT scans in grading hepatocellular carcinoma (HCC). Totally 39 patients (42 lesion samples) with pathologically confirmed HCC who underwent tri-phasic CT scans were enrolled. HCC lesions were divided into non-poorly differentiated HCC (NP-HCC; n = 31) and poorly differentiated HCC (pHCC; n = 11). All lesions were divided into 5 groups according to the attenuation on different CT enhancement phase. The values of tumor attenuation on different scanning phases were measured. The following parameters were calculated: arterial enhancement fraction (AEF), portal venous supply coefficient (PVC), and hepatic arterial supply coefficient (HAC). The relationship of perfusion parameters with the histological grade of HCC was analyzed. Receiver operating characteristic curves were generated. No significant correlation was observed between the perfusion parameters and tumor grading. Only HAC showed a non-significant trend in different grades of HCC (pHCC < NP-HCC; P = .07). The pHCC cases had significantly decreased values of tumor attenuation on the unenhanced phase (TAu), tumor attenuation on the portal phase portal phase (TAp), and equilibrium phase (TAe) (P < .01). The difference of tumor attenuation between the portal phase and the unenhanced phase (TAp-TAu) of the pHCC cases was decreased than that of the NP-HCC cases (P < .01), whereas the difference of attenuation between the equilibrium phase and portal phase (TAe-TAp) was significantly higher in the pHCC cases than that in the NP-HCC cases (P < .01). TAe-TAp had the highest area under the curve. The number of tumor enhancement pattern in Group 5 of HCCs with a diameter of 3 cm or more was significantly more than that of HCCs with a diameter of less than 3 cm or with other different enhancement patterns (P < .01). Histological HCC grading cannot be predicted by the perfusion parameters derived from traditional tri-phasic CT scans, whereas the tumor attenuation on different phases and the tumor attenuation differences among different phases, especially the mean value of TAe-TAp, might be useful for non-invasive prediction on the degree of HCC differentiation.
Experiences of women seeking post-abortion care services in a Regional Hospital in Ghana

Introduction Abortions remain one of the highest contributors to maternal deaths in Ghana. In 2003, a policy on post-abortion care was introduced to help reduce abortion-related mortality and morbidity. However, depending on the method of pregnancy termination; women encounter varying experiences. This study examines the experiences of women seeking post-abortion care services in a Regional Hospital in Ghana. Materials and methods In-depth interview technique was used to collect data from 20 purposively selected post-abortion care clients at the Volta Regional Hospital. Data were analysed manually using a qualitative content analysis technique. Results The study found that medical abortion was the main method of pregnancy termination used by women who participated in the study to induce abortion. Spontaneous abortion, however, was attributed mainly to engaging in activities that required the use of excessive energy and travelling on bad roads by pregnant women. The study also revealed that, women do not seek early post-abortion care services due to stigma and poverty. Conclusions We found that severity of pain from complications, stigma and financial constraints were factors that influenced women’s decision to seek post-abortion care services. Our findings also suggest that women who experienced spontaneous abortion mainly received financial and emotional support from partners and other family members. To encourage women to seek early post-abortion care services, the Ministry of Health and the Ghana Health Service should take pragmatic steps to educate women on the dangers associated with delay in seeking post-abortion care services and the factors that expose women to spontaneous abortions.
Fully automatic d-lactate assay using a modified commercially available method

Abstract Intestinal infarction is the fast-evolving endpoint of impaired blood perfusion to an intestinal segment which may have fatal outcome. Early diagnosis and treatment within 6 h reduce mortality. Currently, d-lactate is a promising biomarker, however, not available in the acute clinical setting. The aim of this study is implementation of d-lactate analysis in a routine clinical setting. We used a spectrophotometric method, based on enzymatic oxidation of d-lactate by d-lactate dehydrogenase (D-LDH) coupled to the reduction of nicotinamide-adenine dinucleotide (NAD+). The amount of NADH formed in this reaction is equivalent to d-lactate. The primary concern in this method is interfering NADH formed by oxidation of l-lactate by l-lactate dehydrogenase (L-LDH). A commercially available kit for d-lactate measurement was implemented on our existing automated routine laboratory equipment including pH-inactivation of L-LDH. Our setup fulfilled clinical quality goals. We were able to measure d-lactate with an acceptable performance of the analysis and a short turn-around time. The method can be used to distinguish between the expected cut-off for intestinal ischemia around 0.3 mM and the upper reference limit of 0.05 mM. With a turnaround time of just 9 min, the analysis has potential as a readily available detection of circulating d-lactate for early diagnosis of intestinal ischemia.
Controllable synthesis of SnO2 photocatalyst with superior photocatalytic activity for the degradation of methylene blue dye solution

ABSTRACT SnO2 photocatalyst was successfully synthesised by novel chemical route in hydrothermal environment and annealed at two different temperatures viz 550 and 600 °C, respectively. The crystal structure, optical properties, surface and bulk morphology have been characterised using various tools like X-ray diffraction (XRD), UV visible spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscope (TEM) and scanning electron microscope (SEM). Cubic, spheres and porous like morphology of SnO2 photocatalyst was successfully confirmed using SEM micrographs and TEM. In addition to this the photocatalytic activity was evaluated towards the degradation of methylene blue dye solution. SnO2 photocatalyst annealed at 600 °C exhibits excellent photocatalytic efficiency which may be attributed to the unique morphology, high crystalline nature and charge separation. The photocatalyst efficiency was further tested towards the concentration of dye, catalyst dosage and pH of the dye. The involvement of •OH in the photocatalytic reaction was evidenced using trapping experiment by employing different scavengers. The photocatalyst was moderately active, stable upto its fifth usage and stability of the photocatalyst before and after the photocatalytic reaction was also been studied using XRD and SEM.
Sulindac Modulates the Response of Proficient MMR Colorectal Cancer to Anti–PD-L1 Immunotherapy

Immune-checkpoint inhibitor (ICI) therapy has been widely used to treat different human cancers, particularly advanced solid tumors. However, clinical studies have reported that ICI immunotherapy benefits only ∼15% of patients with colorectal cancer, specifically those with tumors characterized by microsatellite instability (MSI), a molecular marker of defective DNA mismatch repair (dMMR). For the majority of patients with colorectal cancer who carry proficient MMR (pMMR), ICIs have shown little clinical benefit. In this study, we examined the efficacy of sulindac to enhance the response of pMMR colorectal cancer to anti–PD-L1 immunotherapy. We utilized a CT26 syngeneic mouse tumor model to compare the inhibitory effects of PD-L1 antibody (Ab), sulindac, and their combination on pMMR colorectal cancer tumor growth. We found that mice treated with combination therapy showed a significant reduction in tumor volume, along with increased infiltration of CD8+ T lymphocytes in the tumor tissues. We also demonstrated that sulindac could downregulate PD-L1 by blocking NF-κB signaling, which in turn led to a decrease in exosomal PD-L1. Notably, PD-L1 Ab can be bound and consumed by exosomal PD-L1 in the blood circulation. Therefore, in combination therapy, sulindac downregulating PD-L1 leads to increased availability of PD-L1 Ab, which potentially improves the overall efficacy of anti–PD-L1 therapy. We also show that low-dose sulindac does not appear to have a systemic inhibitory effect on prostaglandin E2 (PGE2). In conclusion, our findings provide unique insights into the mechanism of action and efficacy for sulindac as an immunomodulatory agent in combination with anti–PD-L1 therapy for the treatment of pMMR colorectal cancer.
Association of negative symptoms with cognitive impairment in Chinese Han patients with chronic schizophrenia

Abstract Objective Cognitive impairment is an essential feature of schizophrenia; however, the relationship between clinical psychiatric symptoms with cognitive impairment is still unclear. Therefore, we aimed to assess cognitive deficits and the relationship between clinical symptoms and cognitive function in patients with chronic schizophrenia, which provide a reference guide for psychiatrists. Methods We compared the cognitive function in 312 schizophrenia inpatients and 397 healthy controls by using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The positive and negative symptom scale (PANSS) was used to assess the clinical symptoms of the patients. Results Analysis of covariance showed that the RBANS total and four index scores (all p < 0.001) were significantly lower in patients than healthy controls. After Bonferroni correction, Pearson correlation analysis showed that there was a significant negative association between PANSS negative symptom subscale and RBANS total score and all 5 domain scores (all p < 0.01). Further regression analysis showed that negative symptoms, age, age of onset, and antipsychotic dose were important independent predictors of cognitive deficits. Conclusions Our findings suggest that patients with chronic schizophrenia exhibit cognitive deficits compared with healthy people. Negative symptoms and some clinical variables are associated with cognitive impairment in patients with schizophrenia. KEYPOINTS This study indicates that patients with chronic schizophrenia have extensive cognitive impairment shown on RBANS except for the visuospatial/constructional domain. Cognitive impairment in patients is associated with age, negative symptoms, age of onset, and antipsychotic dose. There is a significant negative association between cognitive deficits and negative symptoms in patients with chronic schizophrenia. The results of this study need to be confirmed in future studies with longitudinal designs with a large and sex-balanced sample in first-episode drug naïve patients with schizophrenia.
Take Your Word or Tone for It? European American and Chinese Children's Attention to Emotional Cues in Speech.

Cultural experiences can influence how people attend to different emotional cues. Whereas semantic content explicitly describes feelings, vocal tone conveys implicit information regarding emotions. This cross-cultural study examined children's attention to emotional cues in spoken words. The sample consisted of 121 European American (EA) and 120 Chinese children (4-9 years old). Each child played two computer games in which they listened to spoken words and judged the pleasantness of either the word meaning (Word game) or the vocal tone (Tone game) while ignoring the other aspect. Chinese children paid more spontaneous attention to vocal tones and less to word meanings than did EA children. These findings shed critical light on the role of culture in shaping affective cognitive processes during development.
Cardiovascular risk factors and autonomic indices in relation to fatal and non-fatal coronary events

Objective Mortality caused by coronary artery disease has markedly decreased in recent years. However, a substantial proportion of patients suffering a coronary event (CE) die within the first day, most of them out of hospital. We aimed to investigate how established cardiovascular (CV) risk factors and CV autonomic indices associate with fatal versus non-fatal CEs in the population. Methods 33 057 individuals (mean age; 45.6 years; 10 773 women) free of coronary artery disease at baseline were included. Baseline examination, including assessment of traditional CV risk factors and autonomic indices such as heart rate and orthostatic reaction, was performed during 1974–1992, after which the subjects were monitored for incident CV disease. The Lunn-McNeil competing risks approach with a prespecified multivariable model was used to assess differences in risks for fatal and non-fatal CEs in relation to baseline CV risk factors. Results During follow-up period of 29.7 years, 5494 subjects (6.10/1000 person-years) had first CE; 1554 of these were fatal. Age, male gender, smoking, body mass index (BMI), blood pressure, pulse pressure and resting heart rate had stronger relationships with fatal CE than with non-fatal events. The effects of diabetes, serum cholesterol, antihypertensive treatment and orthostatic blood pressure responses were similar for fatal and non-fatal CE. Conclusions Several cardiovascular risk factors, such as smoking, high BMI, blood pressure and high resting heart rate, were preferentially associated with fatal compared with non-fatal CEs. These observations may require special attention in the overall efforts to further reduce coronary artery disease mortality.
Peptidoglycan Contribution to the B Cell Superantigen Activity of Staphylococcal Protein A

The LysM domain is found in all kingdoms of life. While their function in mammals is not known, LysM domains of bacteria and their phage parasites are associated with enzymes that cleave or remodel peptidoglycan. ABSTRACT Staphylococcus aureus causes reiterative and chronic persistent infections. This can be explained by the formidable ability of this pathogen to escape immune surveillance mechanisms. Cells of S. aureus display the abundant staphylococcal protein A (SpA). SpA binds to immunoglobulin (Ig) molecules and coats the bacterial surface to prevent phagocytic uptake. SpA also binds and cross-links variable heavy 3 (VH3) idiotype (IgM) B cell receptors, promoting B cell expansion and the secretion of nonspecific VH3-IgM via a mechanism requiring CD4+ T cell help. SpA binding to antibodies is mediated by the N-terminal Ig-binding domains (IgBDs). The so-called region X, uncharacterized LysM domain, and C-terminal LPXTG sorting signal for peptidoglycan attachment complete the linear structure of the protein. Here, we report that both the LysM domain and the LPXTG motif sorting signal are required for the B cell superantigen activity of SpA in a mouse model of infection. SpA molecules purified from staphylococcal cultures are sufficient to exert B cell superantigen activity and promote immunoglobulin secretion as long as they carry intact LysM and LPXTG motif domains with bound peptidoglycan fragments. The LysM domain binds the glycan chains of peptidoglycan fragments, whereas the LPXTG motif is covalently linked to wall peptides lacking glycan. These findings emphasize the complexity of SpA interactions with B cell receptors. IMPORTANCE The LysM domain is found in all kingdoms of life. While their function in mammals is not known, LysM domains of bacteria and their phage parasites are associated with enzymes that cleave or remodel peptidoglycan. Plants recognize microbe-associated molecular patterns such as chitin via receptors endowed with LysM-containing ectodomains. In plants, such receptors play equally important roles in defense and symbiosis signaling. SpA of S. aureus carries a LysM domain that binds glycan strands of peptidoglycan to influence defined B cell responses that divert pathogen-specific adaptive immune responses.
Effect of Portulaca Oleracea (purslane) extract on liver enzymes, lipid profile, and glycemic status in nonalcoholic fatty liver disease: A randomized, double‐blind clinical trial

Purslane (Portulaca oleracea L.) is the richest green leafy vegetable source of omega‐3, especially alpha linolenic acid (ALA). Experimental studies have shown beneficial effects of purslane extract on liver enzymes. The aim of the present study was to examine the effect of purslane hydroalcohoic extract in patients with non‐alcoholic fatty liver disease (NAFLD). In a randomized double‐blinded clinical trial, 74 patients were randomly assigned to receive either 300 mg purslane extract or placebo capsules for 12 weeks. Compared with baseline, alanine aminotransferase (ALT) (−9 [−17, 0.50] mg/dl; p = .007), aspartate aminotransferase (AST) (−4 [−10, −0.50] mg/dl; p = .001), gamma glutamyltransferase (GGT) (−6.21 ± 9.85 mg/dL; p < .001), fasting blood glucose (FBG) (−8 [−11, −1.50] mg/dl; p < .001) insulin resistance (−0.95 ± 2.23; p = .020), triglyceride (−20 [−67.50, 3.50] mg/dl; p = .010), and low‐density lipoprotein cholesterol (LDL‐C) (−5 [−12, −1] mg/dl; p < .001) decreased significantly in the purslane group. At the end of study, no significant changes were observed in liver steatosis grade, insulin, liver enzymes, total bilirubin, lipid profile, and blood pressure between the two groups. The findings of our study show that purslane extract at the dose of 300 mg/day for 12 weeks has no significant effects on liver enzymes, lipid profile, and glycemic indices in patients with NAFLD.