Miracle-dz/UniFAR-FTUs huggingface dataset:
Screening tests for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus in blood donors: Evaluation of two chemiluminescent immunoassay systems

Abstract Automated chemiluminescent immunoassays (CLIAs) are useful for the detection of hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus 1/2 antigen/antibodies (HIV 1/2 Ag/Ab) in blood donor screening. Eight hundred and forty serum samples were tested for hepatitis B surface antigen (HBsAg), HCV antibodies (anti-HCV), and HIV1/2 Ag/Ab in parallel using 2 different CLIAs (Abbott Architect i2000SR and Roche Cobas e411). The concordance between the 2 systems was high (Cohen's kappa 0.97 for HBsAg, 0.77 for anti-HCV, 0.92 for HIV1/2 Ag/Ab) and the specificity and the positive predictive value were comparable. Among the 12 discrepant results, 11 were false-positive and 1 (reactive by Architect) was true-positive for anti-HCV. Positivity for HBV DNA, HCV RNA, and HIV RNA was recorded in 90.9%, 38.9%, and 100% of true-positive samples, respectively. This study represents the first stringent comparison between Architect i2000SR and Cobas e411 in blood donors. We observed a good correlation and high agreement among HBV, HCV, and HIV with the 2 automated systems.
Cytoplasmic Igα Serine/Threonines Fine-Tune Igα Tyrosine Phosphorylation and Limit Bone Marrow Plasma Cell Formation

Igα serine 191 and 197 and threonine 203, which are located in proximity of the Igα ITAM, dampen Igα ITAM tyrosine phosphorylation. In this study, we show that mice with targeted mutations of Igα S191, 197, and T203 displayed elevated serum IgG2c and IgG2b concentrations and had elevated numbers of IgG2c- and IgG2b-secreting cells in the bone marrow. BCR-induced Igα tyrosine phosphorylation was slightly increased in splenic B cells. Our results suggest that Igα serine/threonines limit formation of IgG2c- and IgG2b-secreting bone marrow plasma cells, possibly by fine-tuning Igα tyrosine-mediated BCR signaling.
Ozone Inhalation Promotes CX3CR1-Dependent Maturation of Resident Lung Macrophages That Limit Oxidative Stress and Inflammation

Inhalation of ambient ozone alters populations of lung macrophages. However, the impact of altered lung macrophage populations on the pathobiology of ozone is poorly understood. We hypothesized that subpopulations of macrophages modulate the response to ozone. We exposed C57BL/6 mice to ozone (2 ppm × 3 h) or filtered air. At 24 h after exposure, the lungs were harvested and digested and the cells underwent flow cytometry. Analysis revealed a novel macrophage subset present in ozone-exposed mice, which were distinct from resident alveolar macrophages and identified by enhanced Gr-1+ expression [Gr-1 macrophages (Gr-1 Macs)]. Further analysis showed that Gr-1+ Macs exhibited high expression of MARCO, CX3CR1, and NAD(P)H:quinone oxioreductase 1. Gr-1+ Macs were present in the absence of CCR2, suggesting that they were not derived from a CCR2-dependent circulating intermediate. Using PKH26-PCL to label resident phagocytic cells, we demonstrated that Gr-1 Macs were derived from resident lung cells. This new subset was diminished in the absence of CX3CR1. Interestingly, CX3CR1-null mice exhibited enhanced responses to ozone, including increased airway hyperresponsiveness, exacerbated neutrophil influx, accumulation of 8-isoprostanes and protein carbonyls, and increased expression of cytokines (CXCL2, IL-1β, IL-6, CCL2, and TNF-α). Our results identify a novel subset of lung macrophages, which are derived from a resident intermediate, are dependent upon CX3CR1, and appear to protect the host from the biological response to ozone.
Seroprevalence of antibodies to tick-borne encephalitis virus and Anaplasma phagocytophilum in healthy adults from western Norway

Abstract The aim of this study was to assess the seroprevalence of antibodies to tick-borne encephalitis virus (TBEV) and Anaplasma phagocytophilum in a healthy adult population from Sogn and Fjordane county in western Norway. Sera from 1, 213 blood donors were analysed for IgG-antibodies to TBEV, and a random subgroup of 301 donors for IgG to A. phagocytophilum. In the TBEV ELISA, five (0.4%) sera were positive. These were all interpreted as “false” positives, as four had received vaccines against flaviviruses, and the remaining was negative for neutralizing antibodies to TBEV. Antibodies to A. phagocytophilum were detected by indirect immunofluorescence in 49 (16.2%) subjects (titer range 80-1280). The results indicate that TBE currently is not endemic in this part of western Norway. However, there is serological evidence of the existence of human granulocytic anaplasmosis in the population.
Chlamydia trachomatis genovars causing urogenital infections in Santiago, Chile

Abstract Background: Chlamydia trachomatis is a common sexually transmitted infection in Chile, but little is known about the genovar distribution in genital infections. Thus, the objective of this study was to determine the distribution of C. trachomatis genovars in such cases. Methods: A total of 522 urogenital specimens, 403 from women and 119 from men, were analyzed for C. trachomatis by nested polymerase chain reaction (PCR) targeting of the ompA gene. Positive specimens were genotyped by DNA sequencing of the amplicons. Results: Sixty-two (11.9%) specimens were positive. Of these, 43 (69.4%) were collected from men and 19 (30.6%) from women (p < 0.0001). Eight genovars were identified in men and seven in women. Genovar E was the most common in both men and women, followed by genovar Da in men, and F in women. Together these three genovars accounted for 84% of infections. Genovar D was the third most common genovar (n = 4). Genovar G was detected in two samples, and sequences of genovars Ba, H, and Ja were each found in single samples. One sample (1.6%) contained mixed sequences. No association was found between gender and specific genovars. Fifty-six (92%) sequences were identical to those reported for the respective reference genovars and the other two have been described in several regions. Conclusions: Our findings add to the results of most studies, which indicate that genovars E, F, and D/Da are the most frequent. No association was found between gender and specific genovars. Despite the heterogeneous population of genovars, most ompA sequences were conserved.
Factors influencing change management in a selected hospital in Saudi Arabia

Saudi Arabia has experienced a number of changes due to revolutionary new findings and technologies, discoveries and new research in the health care arena, which has proven and contradicted a new approach to health care delivery. Demands by patients who have become more educated, the emergence of new or modern disease profiles which demand a new way of approach and a quickening in the pace of change, hurled unfamiliar and often demanding and challenging conditions at management One such change, as addressed in this study, is the change from a paper-based patient record system to a computer based patient information system to which all healthcare professionals in the multidisciplinary team had access to. However, not all change is welcomed, accepted or viewed as necessary by those who have to carry out or use new technologies. Change is harsh, and part of the problem is identifying factors that influence change initiatives. This study addresses the perceptions of nursing personnel of the process of change from a paper-based to a computer based (Quadramed) patient record system. The study design used a quantitative and descriptive approach in which a structured, self-designed questionnaire was used to obtain data from 117 professional nurses at a selected healthcare facility in the Eastern province of the Kingdom of Saudi Arabia. The theoretical framework used for this study was the Model for Change Management as designed by the Prosci Institute for Research, also referred to as the ADKAR Model of Change Management (Awareness, Desire, Knowledge, Ability and Reinforcement). The major findings of this study revealed that 97.44% of the respondents were nonSaudi individuals, and were mainly from the Philippines (69.24%), with (95.65% being female with an average age of 37-42 years. Most (47%) were in possession of specialty qualifications in medical, surgical nursing and experience between 8-10 years, of which 2-3 years had been in Saudi Arabia. In regard to 61.3% of the respondents it was found that they had no prior knowledge of computerised patient records. The nurse managers played a vital role in providing the most information and support to adjust to the system. With reference to the aspect of patient safety, positive feedback about the QCPR was provided by the majority of respondents. Most of the respondents experienced change positively, and 70% indicated that being involved played a major role in their positive attitude. Recommendations include that reasons for change should be more clearly communicated, suggestions for change should be valued more by managers and rumours and uncertainties about change should be addressed as and when appropriate. Key terms: Computerised patient medical record system, Quadramed, ADKAR Model of Change Management, Models of Change Management, resistance to change, change management, Saudi Arabia Stellenbosch University http://scholar.sun.ac.za
Contact-Dependent T Cell Activation and T Cell Stopping Require Talin1

T cell–APC contact initiates T cell activation and is maintained by the integrin LFA-1. Talin1, an LFA-1 regulator, localizes to the immune synapse (IS) with unknown roles in T cell activation. In this study, we show that talin1-deficient T cells have defects in contact-dependent T cell stopping and proliferation. Although talin1-deficient T cells did not form stable interactions with APCs, transient contacts were sufficient to induce signaling. In contrast to prior models, LFA-1 polarized to T cell–APC contacts in talin1-deficient T cells, but vinculin and F-actin polarization at the IS was impaired. These results indicate that T cell proliferation requires sustained, talin1-mediated T cell–APC interactions and that talin1 is necessary for F-actin polarization and the stability of the IS.
Stromal Endothelial Cells Establish a Bidirectional Crosstalk with Chronic Lymphocytic Leukemia Cells through the TNF-Related Factors BAFF, APRIL, and CD40L

Chronic lymphocytic leukemia (CLL) is a clonal B cell disorder of unknown origin. Accessory signals from the microenvironment are critical for the survival, expansion, and progression of malignant B cells. We found that the CLL stroma included microvascular endothelial cells (MVECs) expressing BAFF and APRIL, two TNF family members related to the T cell-associated B cell-stimulating molecule CD40L. Constitutive release of soluble BAFF and APRIL increased upon engagement of CD40 on MVECs by CD40L aberrantly expressed on CLL cells. In addition to enhancing MVEC expression of CD40, leukemic CD40L induced cleavases that elicited intracellular processing of pro-BAFF and pro-APRIL proteins in MVECs. The resulting soluble BAFF and APRIL proteins delivered survival, activation, Ig gene remodeling, and differentiation signals by stimulating CLL cells through TACI, BAFF-R, and BCMA receptors. BAFF and APRIL further amplified CLL cell survival by upregulating the expression of leukemic CD40L. Inhibition of TACI, BCMA, and BAFF-R expression on CLL cells; abrogation of CD40 expression in MVECs; or suppression of BAFF and APRIL cleavases in MVECs reduced the survival and diversification of malignant B cells. These data indicate that BAFF, APRIL, and CD40L form a CLL-enhancing bidirectional signaling network linking neoplastic B cells with the microvascular stroma.
Isoform-Selective HDAC Inhibition for the Treatment of Lupus Nephritis

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease requiring a genetic predisposition coupled with an environmental trigger in order for initiation of disease. While the exact pathoaetiology has yet to be determined, both B and T cell dysregulation are thought to contribute to disease. Histone deacetylases (HDACs) are a class of enzymes that hydrolyze the lysine bound acetyl group in both histone and non-histone proteins thereby altering protein structure and function. While the use of pan-HDAC inhibitors has proven to be effective for the treatment of a number of acute diseases, they may not be viable as therapeutics for chronic disease due to cytotoxicity and adverse side effects following long term treatment. We sought to determine whether treatment with a class I and II HDAC inhibitor (HDACi) or a specific HDAC6i would be able to ameliorate disease in lupus-prone NZB/W mice. We found that both the class I and II HDACi (ITF2357) and the HDAC6i (ACY-738) were able to decrease SLE markers of disease including splenomegaly, proteinuria, and anti-dsDNA and IgG production in the sera. Treatment with ITF2357 resulted in an increase in the number of immunosuppressive regulatory T (Treg) cells and a decrease in the pro-inflammatory Th17 phenotype. Furthermore, ITF2357 was found to increase Foxp3 acetylation leading to increased Foxp3 stability allowing for differentiation into the Treg phenotype. ACY-738 treatment was able to correct aberrant bone marrow B cell differentiation while also increasing the number of splenic Treg cells in NZB/W mice. These results suggest that HDAC inhibition is able to ameliorate SLE in NZB/W mice by altering aberrant T and B cell differentiation. Additional studies were performed to further examine the expression and function of different HDAC
Monocytic Thrombomodulin Triggers LPS- and Gram-Negative Bacteria-Induced Inflammatory Response

Sepsis results from the host hyperinflammatory response to bacterial infection, causing multiple organ failure and high mortality. We previously demonstrated that LPS binds to monocytic membrane-bound thrombomodulin (TM), but the role of monocytic TM in LPS-induced inflammation remains unknown. In this study, we demonstrated that TM knockdown in human monocytic cells attenuated LPS-induced signaling pathways and cytokine production. Coimmunoprecipitation and immunofluorescence assays showed that monocytic TM interacted with the LPS receptors, CD14 and TLR4/myeloid differentiation factor-2 (MD-2) complex, indicating that it binds to LPS and triggers an LPS-induced inflammatory response by interacting with the CD14/TLR4/MD-2 complex. We also found that monocytic TM knockdown reduced cytokine production induced by Gram-negative bacteria Klebsiella pneumoniae, suggesting that monocytic TM plays an important role in Gram-negative bacteria-induced inflammation. To further investigate the function of monocytic TM in vivo, myeloid-specific TM-deficient mice were established and were found to display improved survival that resulted from the attenuation of septic syndrome, including reduced systemic inflammatory response and resistance to bacterial dissemination, after K. pneumoniae infection or cecal ligation and puncture surgery. The inhibition of bacterial dissemination in mice with a deficiency of myeloid TM may be caused by the early increase in neutrophil infiltration. Therefore, we conclude that monocytic TM is a novel component in the CD14/TLR4/MD-2 complex and participates in the LPS- and Gram-negative bacteria-induced inflammatory response.
Is well-being associated with lower urinary tract symptoms in patients with stroke?

Abstract Objective. This study aimed to assess self-reported well-being in a clinical sample of stroke patients and to identify possible associations with prevalence, severity and bother of lower urinary tract symptoms (LUTS). Material and methods. A cross-sectional, clinical survey was initiated whereby stroke patients were invited to complete The WHO-Five Well-Being Index (WHO-5) and a LUTS instrument, the Danish Prostatic Symptom Score (DAN-PSS-1) questionnaire. Of 519 stroke patients invited, 482 subjects were eligible and 407 (84%) respondents answered the questionnaires. Results. Poor well-being (sum score <13) was reported by 22% of all stroke patients, for women 29% and for men 14%. Depression (sum score <8) was reported by 10%, for women 11% and for men 8%. Poor well-being was significantly (p < 0.01) associated with severity and bother of LUTS. Likewise, poor well-being was significantly (p < 0.001) associated with the prevalence of four different symptom groups of LUTS. Conclusions. The results indicate that poor well-being is present in stroke patients with LUTS, especially in women. Likewise, the data showed significant association between poor well-being and LUTS. Screening for well-being and LUTS in stroke patients is strongly recommended.
Long-term experience with surgical treatment of selected patients with bladder pain syndrome/interstitial cystitis

Abstract Objective. The role of major surgery in patients with bladder pain syndrome/interstitial cystitis (BPS/IC) is not fully established. This report presents a single-institution experience with major surgery in patients with disabling BPS/IC where conservative treatment had failed. Material and methods. Forty-one patients (34 women, seven men) with BPS/IC refractory to conservative treatment underwent major surgery from 1983 to 2004. Surgical approach was determined on a case-by-case basis. Postoperative pain and satisfaction were assessed by a questionnaire. Results. Cystectomy was the primary procedure in five patients. The remaining 36 patients were primarily operated on with subtotal cystectomy and bladder augmentation (n = 16) or supravesical urinary diversion with intact bladder (n = 20). Thirteen of these patients were later operated on with cystectomy due to persisting pain 12 (6–146) months after the primary procedure. The questionnaire was answered by 38 of 41 patients after a median follow-up of 66 (6–238) months. In total, 28 patients (74%) were free of pain, and 26 patients (68%) were satisfied with the end result. There was no difference in reported pain between cystectomized and non-cystectomized patients. When comparing patients who reported pain at follow-up with those who did not report pain, preoperative length of symptoms was significantly increased, with 12.1 compared to 5.4 years (p = 0.02). Conclusions. Major surgery is associated with good symptom relief in strictly selected patients with disabling BPS/IC, where conservative treatment has failed. Extended preoperative duration of symptoms may be a predictor for persisting pain after major surgery for BPS/IC.
Antigen-Specific IL-2 Secretion Correlates with NK Cell Responses after Immunization of Tanzanian Children with the RTS,S/AS01 Malaria Vaccine

RTS,S/AS01, a vaccine targeting pre-erythrocytic stages of Plasmodium falciparum, is undergoing clinical trials. We report an analysis of cellular immune response to component Ags of RTS,S—hepatitis B surface Ag (HBs) and P. falciparum circumsporozoite (CS) protein—among Tanzanian children in a phase IIb RTS,S/AS01E trial. RTS,S/AS01 E vaccinees make stronger T cell IFN-γ, CD69, and CD25 responses to HBs peptides than do controls, indicating that RTS,S boosts pre-existing HBs responses. T cell CD69 and CD25 responses to CS and CS-specific secreted IL-2 were augmented by RTS,S vaccination. Importantly, more than 50% of peptide-induced IFN-γ+ lymphocytes were NK cells, and the magnitude of the NK cell CD69 response to HBs peptides correlated with secreted IL-2 concentration. CD69 and CD25 expression and IL-2 secretion may represent sensitive markers of RTS,S-induced, CS-specific T cells. The potential for T cell-derived IL-2 to augment NK cell activation in RTS,S-vaccinated individuals, and the relevance of this for protection, needs to be explored further.
Increased Expression of SLAM Receptors SLAMF3 and SLAMF6 in Systemic Lupus Erythematosus T Lymphocytes Promotes Th17 Differentiation

Altered T cell function in systemic lupus erythematosus (SLE) is determined by various molecular and cellular abnormalities, including increased IL-17 production. Recent evidence suggests a crucial role for signaling lymphocyte activation molecules (SLAMs) in the expression of autoimmunity. In this study, we demonstrate that SLAMF3 and SLAMF6 expression is increased on the surface of SLE T cells compared with normal cells. SLAM coengagement with CD3 under Th17 polarizing conditions results in increased IL-17 production. SLAMF3 and SLAMF6 T cell surface expression and IL-17 levels significantly correlate with disease activity in SLE patients. Both naive and memory CD4+ T cells produce more IL-17 in response to SLAM costimulation as compared with CD28 costimulation. In naive CD4+ cells, IL-17 production after CD28 costimulation peaks on day 3, whereas costimulation with anti-SLAMF3 and anti-SLAMF6 Abs results in a prolonged and yet increasing production during 6 d. Unlike costimulation with anti-CD28, SLAM costimulation requires the presence of the adaptor molecule SLAM-associated protein. Thus, engagement of SLAMF3 and SLAMF6 along with Ag-mediated CD3/TCR stimulation represents an important source of IL-17 production, and disruption of this interaction with decoy receptors or blocking Abs should mitigate disease expression in SLE and other autoimmune conditions.
Recruitment of Memory B Cells to Lymph Nodes Remote from the Site of Immunization Requires an Inflammatory Stimulus

Successful recall Ab responses require recruitment of quiescent memory B cells to secondary lymphoid organs. However, the cellular dynamics of memory cells responding to local antigenic challenge at lymphoid sites distal from the initial Ag encounter are not well understood. We show in this study that memory B cells generated following s.c. immunization in one footpad generate secondary responses to soluble Ag given i.p. but not to Ag given s.c. in the contralateral footpad unless LPS is coadministered. Memory B cells do not express CD62L, and CD62L−ve cells cannot enter lymph nodes unless LPS-mediated inflammation is induced there. Functional TLR4 is required on the B cells, as well as on non-B cells, in the lymph node to achieve full recruitment. Furthermore, splenectomized mice fail to respond to such inflammatory s.c. challenge in contralateral footpads, unlike lymphadenectomized mice lacking the original draining lymph nodes. Splenectomized mice also fail to respond to i.p. challenge with soluble Ag. Together, these data indicate that, unlike the central memory pool of T cells, which circulates through resting lymph nodes, the majority of long-lived memory B cells are spleen resident and require inflammatory signals for mounting recall responses at distal challenge sites.
Protein Kinase C-θ Inhibits Inducible Regulatory T Cell Differentiation via an AKT-Foxo1/3a–Dependent Pathway

Protein kinase C (PKC)-θ has been shown to be a critical TCR signaling molecule that promotes the activation and differentiation of naive T cells into inflammatory effector T cells. In this study, we demonstrate that PKC-θ–mediated signals inhibit inducible regulatory T cell (iTreg) differentiation via an AKT-Foxo1/3A pathway. TGF-β–induced iTreg differentiation was enhanced in PKC-θ−/− T cells or wild-type cells treated with a specific PKC-θ inhibitor, but was inhibited by the PKC-θ activator PMA, or by CD28 crosslinking, which enhances PKC-θ activation. PKC-θ−/− T cells had reduced activity of the AKT kinase, and the expression of a constitutively active form of AKT in PKC-θ−/− T cells restored the ability to inhibit iTreg differentiation. Furthermore, knockdown or overexpression of the AKT downstream targets Foxo1 and Foxo3a was found to inhibit or promote iTreg differentiation in PKC-θ−/− T cells accordingly, indicating that the AKT-Foxo1/3A pathway is responsible for the inhibition of iTreg differentiation of iTregs downstream of PKC-θ. We conclude that PKC-θ is able to control T cell-mediated immune responses by shifting the balance between the differentiation of effector T cells and inhibitory Tregs.