Miracle-dz/UniFAR-FTUs huggingface dataset:
Sleep Apnea Syndrome in an Elderly Population Admitted to a Geriatric Unit: Prevalence and Effect on Cognitive Function

Background Sleep apnea leads to cognitive impairment in older patients, but its association with neurodegeneration remains controversial, and most studies do not distinguish between the more common obstructive form (OSAS) and the rarer central form (CSAS). Objective The purpose of this study was to assess the prevalence of the different forms of sleep apnea in a cohort of cognitively impaired elderly patients (>70 years) and to investigate their associations with cognitive deficit, weighted against known risk factors for neurodegeneration. Methods Overnight polygraphy was performed for 76 consecutive patients admitted to our geriatric unit. Their cognitive function was assessed using the Mini Mental-State Exam (MMSE), Mattis Dementia Rating Scale (MDRS) and Stroop test. Multivariable analyses were performed to determine associations between cognitive function and independent variables describing demographics, sleep apnea measures, and cardiovascular risk factors. Results The cohort comprised 58 women and 18 men aged a mean of 84 years (range, 73–96). Sleep apnea syndrome (SAS) was diagnosed in 48 patients (63%), of which 31 (41%) with OSAS and 17 (22%) with CSAS. Multivariable regression analysis revealed that MDRS was lower in patients with OSAS (β = −10.03, p = 0.018), that Stroop Colors and Words delays increased with AHI (β = 0.17, p = 0.030 and β = 0.31, p = 0.047) and that that Stroop Interference delay was higher in patients with CSAS (β = 24.45, p = 0.002). Conclusion Sleep apnea is thus highly prevalent in elderly patients with cognitive impairment. OSAS was associated with lower general cognitive function, while CSAS was only associated with increased Stroop Interference delays. Elderly patients with cognitive deficit could benefit from sleep apnea screening and treatment.
CXCL1 as an Unfavorable Prognosis Factor Negatively Regulated by DACH1 in Non-small Cell Lung Cancer

Background: Interaction between cancer cells with microenvironment is essential for cancer progression, therapeutic resistance and prognosis. Chemokine CXCL1 shows variable roles in the development of cancers. DACH1 has been considered as a tumor suppressor and represses the expressions of several chemokines. The relationship between CXCL1 and DACH1 in non-small cell lung cancer (SCLC) deserves further investigation. Methods: Immunohistochemistry staining was performed on tumor tissue microarrays from lung cancer patients to detect CXCL1 protein. The CXCL1 concentration in the serum of adenocarcinoma patients was measured by ELISA. The CXCL1 protein secreted by cancer cell lines was detected by SearchLight proteome array and human cytokine antibody array. The meta-analysis of CXCL1 expression form public databases was performed and correlation between CXCL1 and DACH1 was analyzed. Moreover, the association between clinicopathological features and prognosis with CXCL1 and DACH1 was analyzed by tissue array and KM-plotter from public database. Results: The protein abundance of CXCL1 in lung cancer tissues was significantly higher than that in adjacent normal tissues. CXCL1 was closely related to TNM stage, tumor size, and lymph node metastasis and predicted worse overall survival in adenocarcinoma. The level of CXCL1 in the peripheral blood of adenocarcinoma patients also significantly elevated and positively related with clinical stage. The meta-analysis demonstrated that CXCL1 mRNA level was increased in lung cancer tissues and high level of CXCL1 indicated tumor progression in lung adenocarcinoma. In addition, public database analyses showed that CXCL1 negatively correlated with DACH1. Stable overexpressing DACH1 in cultured lung cancer cells remarkably decreased CXCL1 protein. Moreover, ectopic expression of DACH1 significantly inhibited the expression of CXCL1, Ki67, and cyclin D1 in tumor tissues compared with A549 cells with empty vector. Survival analysis showed that high CXCL1 and low DACH1 indicated poor overall survival and progression-free survival. Conclusion: CXCL1 is closely associated with tumor progression and poor survival. DACH1 significantly inhibits the expression of CXCL1 and indicates good prognosis. Therefore, combined detection of CXCL1 and DACH1 could more precisely predict prognosis of lung adenocarcinoma.
Prognosis of Patients With Testicular Carcinoma Is Dependent on Metastatic Site

Background: Existing data on the association of metastatic sites and prognosis of patients with metastatic testicular malignancy are limited. In this study, the association of survival outcome and the prognostic value of different metastatic sites in patients with metastatic testicular cancer was investigated. Methods: A dataset from the Surveillance, Epidemiology and End Results (SEER) survey was selected for a retrospective metastatic testicular cancer cohort study. Patients with different metastatic sites were divided into corresponding groups for further analysis. Kaplan-Meier analysis with log-rank test was implemented for comparison of the survival distribution of cases. Multivariate Cox regression models were then applied to analyze the association of distant metastases with survival for all selected patients and subgroup based on different histological type with a single metastatic site. Results: A total of 1,661 patients treated for metastatic testicular malignant tumors between 2010 to 2016 were enrolled in this cohort study. Upon initial diagnosis, 61.9, 15.2, 6.7, 6.4, and 36.2% of patients were found to have lung, liver, bone, brain, and distant lymph nodes metastatic sites, respectively. Patients with lung, liver, or bone metastases showed more undesirable prognosis for overall survival (OS) and cancer-specific survival (CSS), in contrast with those with distant lymph node metastases (all P < 0.05). In comparison with patients with more than one metastatic site, those with a single metastasis had extended OS and CSS (both P < 0.001). In patients with a single metastatic site, Kaplan-Meier analysis and multivariate Cox regression demonstrated the association of bone and liver with the worst two groups of OS and CSS. Multivariate Cox models based on histological type showed different prognostic values of metastases in patients with seminoma or non-seminomatous germ cell tumors. Conclusion: There is much heterogeneity in the oncological outcome of site-specific metastatic patients. Metastatic profiles and the prognostic value of metastases are dependent on the histological type in TC patients. Distant lymph nodes and lung metastases indicate favorable prognostic factors, while bone and liver metastases indicate negative survival outcomes in TC.
Plasmid Display for Stabilization of Enzymes Inside the Cell to Improve Whole-Cell Biotransformation Efficiency

Recombinant whole-cell biocatalysts are widely used for biotransformation of valuable products. However, some key enzymes involved in biotransformation processes are unstable and cannot be easily expressed in the functional form. In this study, we describe a versatile platform for enzyme stabilization inside the cell: Intracellularly Immobilized Enzyme System (IIES). A 1,2-fucosyltransferase from Pedobactor saltans (PsFL) and a 1,3-fucosyltransferase from Helicobacter pylori (HpFL), chosen as model proteins, were fused with Oct-1 DNA-binding domain, which mediated the formation of a plasmid–protein complex. Oct-1 fusion enabled both soluble and stable expression of recombinant proteins in the cytoplasm because the fusion proteins were stabilized on the plasmid like immobilized enzymes bound to solid surface. As a result, Oct-1-fusion proteins exhibited significantly greater product titer and yield than non-fusion proteins. Use of fusion proteins PsFL-Oct-1 with C-terminal Oct-1 and Oct-1-PsFL with N-terminal Oct-1 resulted in ~3- and ~2-fold higher 2′-fucosyllactose titers, respectively, than with the use of PsFL alone. When Oct-1 was fused to HpFL, which requires dimerization through heptad repeats, almost two times more 3-fucosyllactose was produced. Fucosyllactose has been used as a food additive because it has various beneficial effects on human health. We anticipate that IIES using Oct-1 fusion protein developed in this study can be applied to stabilize other unstable enzymes.
Perspective of Key Healthcare Professionals on Antimicrobial Resistance and Stewardship Programs: A Multicenter Cross-Sectional Study From Pakistan

Background: Antimicrobial resistance (AMR) is an increasing global threat, and hospital-based antimicrobial stewardship programs (ASPs) are one of the effective approaches to tackle AMR globally. This study was intended to determine the attitude of key healthcare professionals (HCPs), including physicians, nurses, and hospital pharmacists, towards AMR and hospital ASPs. Methods: A cross-sectional study design was used to collect data from HCPs employed in public teaching hospitals of Punjab, Pakistan, from January 2019 to March 2019. A cluster-stratified sampling method was applied. Descriptive statistics, Mann Whitney and Kruskal Wallis tests were used for analysis. Results: A response rate of 81.3% (881/1083) for the surveys was obtained. The majority of the physicians (247/410, 60.2%) perceived AMR to be a serious problem in Pakistani hospitals (p < 0.001). Most of the HCPs considered improving antimicrobial prescribing (580/881, 65.8%; p < 0.001) accompanied by the introduction of prospective audit with feedback (301/881, 75.8%; p < 0.001), formulary restriction (227/881, 57.2%; p = 0.004) and regular educational activities (300/881, 75.6%; p = 0.015) as effective ASP methods to implement hospital ASPs in Pakistan. A significant association was found between median AMR and ASP scores with age, years of experience, and types of HCPs (p < 0.05). Conclusions: The attitude of most of the HCPs was observed to be positive towards hospital-based ASPs regardless of their poor awareness about ASPs. The important strategies, including prospective audit with feedback and regular educational sessions proposed by HCPs, will support the initiation and development of local ASPs for Pakistani hospitals.
Heart and Cardiac Substructure Dose Sparing in Synchronous Bilateral Breast Radiotherapy: A Dosimetric Study of Proton and Photon Radiation Therapy

Background: Synchronous bilateral breast cancer (SBBC) is rare. The purpose of this study was to compare the dosimetric differences in intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), helical tomotherapy (HT), and intensity-modulated proton therapy (IMPT) to find an optimal radiotherapy technique for bilateral breast cancer radiotherapy. Methods: For 11 patients who received synchronous bilateral whole-breast irradiation without local lymph nodal regions, six plans were designed for each patient: IMRT with a single isocenter (IMRT-ISO1), IMRT with two isocenters (IMRT-ISO2), VMAT with a single isocenter (VMAT-ISO1), VMAT with two isocenters (VMAT-ISO2), HT, and IMPT. The differences between the single- and dual-isocentric plans for IMRT and VMAT were compared, and the plan with the better quality was selected for further dosimetric comparisons with IMPT and HT. The plan aimed for a target coverage of at least 95% with the prescription dose of 50 Gy [relative biological effectiveness (RBE)] while minimizing the dose of organs at risk (OARs). Results: IMRT-ISO1 and VMAT-ISO2 plans were adopted for further dosimetric comparisons because of the reduced dose of the heart and/or lungs compared to IMRT-ISO2 and VMAT-ISO1 plans. The dose coverage of the planning target volume (PTV) was significantly higher in IMPT plans than that in all other plans. VMAT and IMPT plans showed the best conformity, whereas IMRT plans showed the worst conformity. Compared to IMRT and VMAT plans, IMPT and HT plans achieved significantly higher dose homogeneity. IMPT plans reduced the mean dose and low dose volume (V5, V10, and V20) of the heart, left anterior descending artery (LAD), and left ventricle (LV). In high-dose volumes of the heart and cardiac substructures, the IMPT, VMAT, and HT techniques showed similar advantages, and IMRT plans increased the values more than other techniques. IMPT plans had the maximal lung and normal tissue sparing but increased the skin dose compared to IMRT and VMAT plans. Conclusions: IMPT plans improve both the target coverage and the OARs sparing, especially for the heart, cardiac substructures (LAD and LV), lungs and normal tissue, in synchronous bilateral breast radiotherapy. VMAT and HT could be selected as suboptimal techniques for SBBC patients.
Profile of Histone H3 Lysine 4 Trimethylation and the Effect of Lipopolysaccharide/Immune Complex-Activated Macrophages on Endotoxemia

Macrophage plasticity is a process that allows macrophages to switch between two opposing phenotypes based on differential stimuli. Interferon γ (IFNγ)-primed macrophages stimulated with lipopolysaccharide (LPS) [M(IFNγ+LPS)] produce high levels of pro-inflammatory cytokines such as IL-12, TNFα, and IL-6 and low levels of the anti-inflammatory cytokine IL-10, while those stimulated with LPS in the presence of the immune complex (IC) [M(IFNγ+LPS+IC)] produce high levels of IL-10 and low levels of IL-12. In this study, we investigated the plasticity between M(IFNγ+LPS) and M(IFNγ+LPS+IC) in vitro and compared one of the active histone marks [histone H3 lysine 4 trimethylation (H3K4me3)] between M(IFNγ+LPS) and M(IFNγ+LPS+IC) using murine bone marrow-derived macrophages. We found that in an in vitro system, macrophages exhibited functional plasticity from M(LPS) to M(LPS+IC) upon repolarization after 2 days of washout period while IFNγ priming before LPS stimulation prevented this repolarization. Phosphorylation of p38, SAPK/JNK, and NF-κB p65 in M(LPS+IC) repolarized from M(LPS) was similar to that in M(LPS+IC) polarized from resting macrophages. To obtain the epigenetic profiles of M(IFNγ+LPS) and M(IFNγ+LPS+IC), the global enrichment of H3K4me3 was evaluated. M(IFNγ+LPS) and M(IFNγ+LPS+IC) displayed marked differences in genome-wide enrichment of H3K4me3. M(IFNγ+LPS+IC) showed increased global enrichment of H3K4me3, whereas M(IFNγ+LPS) showed decreased enrichment when compared to unstimulated macrophages. Furthermore, M(IFNγ+LPS+IC) exhibited high levels of H3K4me3 enrichment in all cis-regulatory elements. At the individual gene level, the results showed increased H3K4me3 enrichment in the promoters of known genes associated with M(IFNγ+LPS+IC), including Il10, Cxcl1, Csf3, and Il33, when compared with those of M(IFNγ+LPS). Finally, we investigated the impact of M(IFNγ+LPS+IC) on the systemic immune response by adoptive transfer of M(IFNγ+LPS+IC) in an LPS-induced endotoxemia model. The cytokine profile revealed that mice with adoptively transferred M(IFNγ+LPS+IC) had acutely reduced serum levels of the inflammatory cytokines IL-1β and IL-p12p70. This study highlights the importance of epigenetics in regulating macrophage activation and the functions of M(IFNγ+LPS+IC) that may influence macrophage plasticity and the potential therapeutic use of macrophage transfer in vivo.
Correlation of Anti-Salmonella Antibodies Between Serum and Saliva Samples Collected From Finisher Pigs

Saliva samples obtained by using absorptive devices, can provide an alternative diagnostic matrix to serum for monitoring disease status in pigs. The aim of this study was to investigate the correlation of anti-Salmonella antibodies between serum and saliva samples collected from pigs. Twenty individual paired serum and saliva samples were collected from a single farm. Anti-Salmonella IgG was detected in individual serum samples using a commercial Salmonella ELISA kit, validated for sera. The same kit was used with a protocol modified by extending incubation time and increasing temperature to test individual saliva samples. Anti-Salmonella IgG antibodies in pig saliva were always detected at a lower level than in the matching serum samples. A correlation (rho = 0.66; p = 0.002) and a moderate agreement (K > 0.62 p = 0.003) was found between individual Salmonella IgG in serum and saliva samples. Both correlation and the agreement levels are moderate. The size of this investigation was small, and further studies are necessary to further confirm these findings. The results of this work provide some evidence that saliva samples have the potential to be used for the diagnosis of Salmonella infection in pig farms.
Mygalin: An Acylpolyamine With Bactericidal Activity

Inappropriate use of antibiotics favors the selection and spread of resistant bacteria. To reduce the spread of these bacteria, finding new molecules with activity is urgent and necessary. Several polyamine analogs have been constructed and used to control microorganisms and tumor cells. Mygalin is a synthetic acylpolyamine, which are analogs of spermidine, derived from the hemolymph of the spider Acanthoscurria gomesiana. The effective activity of polyamines and their analogs has been associated with their structure. The presence of two acyl groups in the Mygalin structure may give this molecule a specific antibacterial activity. The aim of this study was to identify the mechanisms involved in the interaction of Mygalin with Escherichia coli to clarify its antimicrobial action. The results indicated that Mygalin exhibits intense dose and time-dependent bactericidal activity. Treatment of E. coli with this molecule caused membrane rupture, inhibition of DNA synthesis, DNA damage, and morphological changes. The esterase activity increased along with the intracellular production of reactive oxygen species (ROS) after treatment of the bacteria with Mygalin. In addition, this molecule was able to sequester iron and bind to LPS. We have shown that Mygalin has bactericidal activity with underlying mechanisms involving ROS generation and chelation of iron ions that are necessary for bacterial metabolism, which may contribute to its microbicidal activity. Taken together, our data suggest that Mygalin can be explored as a new alternative drug with antimicrobial potential against Gram-negative bacteria or other infectious agents.
Single Eye mRNA-Seq Reveals Normalisation of the Retinal Microglial Transcriptome Following Acute Inflammation

Background: Whether retinal microglia can maintain or restore immune homeostasis during and after inflammation is unclear. We performed single-eye mRNA-sequencing on microglia at different timepoints following a single inflammatory stimulus to characterise their transcriptome during and after resolution of endotoxin-induced uveitis (EIU). Experimental Approach: Cx3cr1CreER:R26-tdTomato (C57BL/6) male heterozygotes were administered tamoxifen via different regimes at 4–5 weeks of age. Four weeks post-tamoxifen, mice were injected intravitreally with 10 ng lipopolysaccharide (endotoxin induced uveitis, EIU). Six-hundred retinal microglia were obtained by FACS from individual naïve retinas and at 4 h, 18 h, and 2 weeks following EIU induction. Samples were sequenced to a depth of up to 16.7 million reads using the SMART-Seq v4 Ultra Low Input RNA kit. The data was analysed using Partek software and Ingenuity Pathway Analysis. Genes were considered differentially-expressed (DEG) if the FDR step-up p-value was ≤0.05 and the fold-change was ≥±2. Results: Flow cytometric analysis indicates that the Cx3cr1CreER:R26-tdTomato strain is both sensitive (>95% tagging) and specific (>95% specificity) for microglia when tamoxifen is administered topically to the eye for 3 days. During “early” activation, 613 DEGs were identified. In contrast, 537 DEGs were observed during peak cellular infiltrate and none at 2 weeks, compared to baseline controls (1,069 total unique DEGs). Key marker changes were validated by qPCR, flow cytometry, and fluorescence microscopy. C5AR1 was identified and validated as a robust marker of differentiating microglial subsets during an LPS response. Conclusion: Using EIU to provide a single defined inflammatory stimulus, mRNA-Seq identified acute transcriptional changes in retinal microglia which returned to their original transcriptome after 2 weeks. Yolk-sac derived microglia are capable of restoring their homeostatic state after acute inflammation.
What “Tears” Remind Us of: An Investigation of Embodied Cognition and Schizotypal Personality Trait Using Pencil and Teardrop Glasses

Facial expressions influence our experience and perception of emotions—they not only tell other people what we are feeling but also might tell us what to feel via sensory feedback. We conducted three experiments to investigate the interaction between facial feedback phenomena and different environmental stimuli, by asking participants to remember emotional autobiographical memories. Moreover, we examined how people with schizotypal traits would be affected by their experience of emotional facial simulations. We found that using a directed approach (gripping a pencil with teeth/lips) while remembering a specific autobiographical memory could successfully evoke participants’ positive (e.g., happy and excited)/negative (e.g., angry and sad) emotions (i.e., Experiment 1). When using indirective environmental stimuli (e.g., teardrop glasses), the results of our experiments (i.e., Experiments 2 and 3) investigating facial feedback and the effect of teardrop glasses showed that participants who scored low in schizotypy reported little effect from wearing teardrop glasses, while those with high schizotypy reported a much greater effect in both between- and within-subject conditions. The results are discussed from the perspective of sense of ownership, which people with schizophrenia are believed to have deficits in.
Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis

Postmenopausal osteoporosis (PMOP) is a metabolic bone disease characterized by decreased bone density and strength due to the imbalance between osteogenesis and osteoclastogenesis. Postmenopausal estrogen withdrawal increases proinflammatory cytokines and increases the serum level of Receptor activator of NF-kB ligand (RANKL)/Osteoprotegerin (OPG), which then leads to the overactivation of osteoclastogenesis. Tetrandrine, a bis-benzylisoquinoline alkaloid, has been widely used in the treatment of rheumatoid arthritis clinically in China. Here, we demonstrate that tetrandrine significantly prevented ovariectomy-induced bone loss and inhibited RANKL-induced osteoclastogenesis. In vivo, we found that intraperitoneal injection of tetrandrine (30 mg/kg) every other day markedly reduced bone loss in ovariectomized mice and the serum levels of TRAcp5b, TNF-a, IL-6, CTX-I, and RANKL/OPG were significantly decreased. In vitro, we found that tetrandrine significantly inhibited osteoclast differentiation in bone marrow monocytes (BMMs) and RAW264.7 cells according to the results of osteoclastogenesis‐related gene expression, tartrate-resistant acid phosphatase (TRAP) staining and actin-ring formation as well as bone resorption assay. Mechanistically, tetrandrine inhibited RANKL‐induced osteoclastogenesis by suppressing NF-kB, Ca2+, PI3K/AKT, and MAPKs signaling pathways. Taken together, our findings suggest that tetrandrine suppresses osteoclastogenesis through modulation of multiple pathways and has potential value as a therapeutic agent for PMOP, especially for those suffering from RA and PMOP at the same time.