Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacogenetic analyses of cisplatin-induced nephrotoxicity indicate a renoprotective effect of ERCC1 polymorphisms.

AIM We investigated whether genetic polymorphisms may contribute to the interpatient variability of cisplatin-induced nephrotoxicity. PATIENTS & METHODS Polymorphisms in the candidate genes GSTM1, GSTT1, OCT1, OCT2, LARP2, ERCC1, XRCC1 and EPO were analyzed for associations with nephrotoxicity in 79 cancer patients receiving cisplatin-containing chemotherapy. RESULTS Higher cisplatin dose was associated with strongly decreased estimated glomerular filtration rates (eGFR) (r(2) = 0.205). Two highly genetically linked polymorphisms in the ERCC1 gene, 8092C>A and Asn118Asn, were significantly associated with change in eGFR, accounting for an additional 13% of interindividual variability. Homozygous carriers of the 8092A allele in ERCC1 showed no reduction in eGFR, compared with the 11.5% mean eGFR decrease in C allele carriers (p = 0.004). Homozygous carriers of the C allele of Asn118Asn showed no reduction in eGFR, compared with the 12.8% mean eGFR decrease seen in T allele carriers (p = 0.047). Polymorphisms in the other candidate genes were not associated with cisplatin-induced nephrotoxicity. CONCLUSION Genetic polymorphisms in ERCC1 may be valuable predictors of cisplatin-induced nephrotoxicity.
A model-based approach for the generation of adaptive user interfaces on portable devices

The development of user interfaces for portable devices offers numerous challenges because of the heterogeneity of the environments in which mobile services are deployed. Thus, an adaptive middleware is needed to generate the user interfaces and adjust their parameters to the different usage scenarios. The middleware needs to enable the separation of the adaptation procedures from the core operations of the interaction. Furthermore, a more structured approach is required to describe the different aspects of the human-computer interaction, which can then be used by the middleware to generate adaptive user interfaces. Specifically, this paper describes the work-in-progress of a run-time middleware that enables the generation of user interfaces on portable devices based on a set of abstract models, and adapting them to the context-of-use. We also present a prototype mobile application to illustrate our approach.
Dendritic cell-based vaccination combined with gemcitabine increases survival in a murine pancreatic carcinoma model

Background: Tumour-specific cytotoxic T lymphocytes (CTLs) can be activated in vivo by vaccination with dendritic cells (DCs). However, clinical responses to DC-based vaccination have only been observed in a minority of patients with solid cancer. Combination with other treatment modalities such as chemotherapy may overcome immunoresistance of cancer cells. It has been shown previously that gemcitabine sensitises human pancreatic carcinoma cells against CTL-mediated lysis. Here, a murine pancreatic carcinoma model was used to investigate whether combination with gemcitabine increases therapeutic efficacy of DC-based vaccination. Methods: Bone marrow-derived DCs from C57BL/6 mice were loaded with UV-irradiated, syngeneic Panc02 carcinoma cells and were administered subcutaneously. For prophylactic vaccination, mice were vaccinated three times at weekly intervals prior to tumour challenge with Panc02 cells. Therapeutic vaccination was started when tumours formed a palpable nodule. Gemcitabine was administered intraperitoneally twice weekly. Results: Prophylactic DC-based vaccination completely prevented subcutaneous and orthotopic tumour development and induced immunological memory as well as tumour antigen-specific CTLs. In the subcutaneous tumour model, therapeutic DC-based vaccination was equally effective as gemcitabine (14% vs 17% survival at day 58 after tumour challenge; controls, 0%). Combination of the two strategies significantly increased survival of tumour-bearing mice (50% at day 58 after tumour challenge). DC-based vaccination also prevented death from pulmonary metastatisation after intravenous injection of Panc02 cells. Conclusion: DC-based immunotherapy may not only be successfully combined with gemcitabine for the treatment of advanced pancreatic carcinoma, but may also be effective in preventing local recurrence or metastatisation in tumour-free patients.
Changing Face of Microglia

Microglia are resident brain cells that sense pathological tissue alterations. They can develop into brain macrophages and perform immunological functions. However, expression of immune proteins by microglia is not synonymous with inflammation, because these molecules can have central nervous system (CNS)–specific roles. Through their involvement in pain mechanisms, microglia also respond to external threats. Experimental studies support the idea that microglia have a role in the maintenance of synaptic integrity. Analogous to electricians, they are capable of removing defunct axon terminals, thereby helping neuronal connections to stay intact. Microglia in healthy CNS tissue do not qualify as macrophages, and their specific functions are beginning to be explored.
Virus Succession Observed during an Emiliania huxleyi Bloom

ABSTRACT Denaturing gradient gel electrophoresis was used as a molecular tool to determine the diversity and to monitor population dynamics of viruses that infect the globally important coccolithophorid Emiliania huxleyi. We exploited variations in the major capsid protein gene from E. huxleyi-specific viruses to monitor their genetic diversity during an E. huxleyi bloom in a mesocosm experiment off western Norway. We reveal that, despite the presence of several virus genotypes at the start of an E. huxleyi bloom, only a few virus genotypes eventually go on to kill the bloom.
Discrimination between maintenance‐ and differentiation‐inducing signals during initial and intermediate stages of positive selection

As well as signaling through the αβ T cell receptor complex, positive selection of immature CD4+ 8+ thymocytes involves additional ill‐defined accessory interactions provided by thymic epithelial cells. Here, we have isolated CD4+ 8+ thymocytes at a pre‐positive selection stage of development (TCR− CD69− 4+ 8+ cells), or after initiation of positive selection (CD69+ 4+ 8+ cells), from mice where the normal lifespan of thymocytes is extended by the presence of a bcl‐2 transgene, to allow us to discriminate between requirements for maintenance and differentiation signals during positive selection. We find that MHC class II+ thymic epithelial cells drive positive selection of TCR− CD69− 4+ 8+ bcl‐2 tg thymocytes to the CD4+ and CD8+ stage, while no such mature subsets are observed when thymocytes are cultured alone or with major histocompatibility complex (MHC) class II+ salivary epithelial cells. However, CD4+ 8+ cells remain in such cultures in considerable numbers, and retain the potential for positive selection if re‐cultured with thymic epithelium, suggesting that thymic epithelial cells provide specific differentiation‐inducing signals for positive selection. In contrast, intermediate CD69+ 4+ 8+ thymocytes show some capacity for phenotypic conversion in the absence of thymic stromal cells although strikingly the single‐positive CD4+ and CD8+ cells generated are not functionally competent. Finally, we show that prior culture of thymic epithelial cells under monolayer conditions abrogates their ability to support the initiation of positive selection, suggesting that the epithelial cell molecules necessary for the provision of differentiation signals during positive selection are down‐regulated under such conditions.
Treatment of osteochondritis dissecans of the knee with a biomimetic scaffold. A prospective multicenter study

Abstract Purpose: the aim of the present study was to evaluate the clinical outcome of the treatment of osteochondritis dissecans (OCD) of the knee with a type-I collagen-hydroxyapatite nanostructural biomimetic osteochondral scaffold. Methods: twenty-three patients affected by symptomatic knee OCD of the femoral condyles, grade 3 or 4 of the International Cartilage Repair Society (ICRS) scale, underwent biomimetic scaffold implantation. The site of the defect was the medial femoral condyle in 14 patients, whereas in 9 patients the lateral femoral condyle was involved. The average size of the defects was 3.5±1.43 cm2. All patients were clinically evaluated using the ICRS subjective score, the IKDC objective score, the EQ-VAS and the Tegner Activity Score. Minimum follow-up was two years. MRI was performed at 12 and 24 months after surgery and then every 12 months thereafter. Results: the ICRS subjective score improved from the baseline value of 50.93±20.6 to 76.44±18.03 at the 12 months (p<0.0005) and 82.23± 17.36 at the two-year follow-up (p<0.0005). The IKDC objective score confirmed the results.The EQ-VAS showed a significant improvement from 3.15±1.09 to 8.15±1.04 (p<0.0005) at two years of follow-up. The Tegner Activity Score improvement was statistically significant (p<0.0005). Conclusions: biomimetic scaffold implantation was a good procedure for treating grade 3 and 4 OCD, in which other classic techniques are burdened by different limitations. This open one-step surgery gave promising stable results at short-term follow-up. Level of evidence: Level IV, therapeutic case series.
Immunocytochemical localization of immunoglobulins in the rat brain: Relationship to the blood‐brain barrier

The central nervous system has been traditionally regarded as an immunologically privileged area. This feature has been in part attributed to the blood‐brain barrier, which provides a restrictive interface to circulating immunoglobulins (IgG). Recent kinetic studies suggest that the barrier to immune proteins is not absolute, but rather may be regulated by a specific transfer mechanism. In this study, we confirm the presence of IgG in the central nervous system by immunocytochemistry and demonstrate a close anatomical relationship between the distribution of this protein and the blood‐brain barrier.
Large scale microblog mining using distributed MB-LDA

In the information explosion era, large scale data processing and mining is a hot issue. As microblog grows more popular, microblog services have become information provider on a web scale, so researches on microblog begin to focus more on its content mining than solely user's relationship analysis before. Although traditional text mining methods have been studied well, no algorithm is designed specially for microblog data, which contain structured information on social network besides plain text. In this paper, we introduce a novel probabilistic generative model MicroBlog-Latent Dirichlet Allocation (MB-LDA), which takes both contactor relevance relation and document relevance relation into consideration to improve topic mining in microblogs. Through Gibbs sampling for approximate inference of our model, MB-LDA can discover not only the topics of microblogs, but also the topics focused by contactors. When faced with large datasets, traditional techniques on single node become less practical within limited resources. So we present distributed MB-LDA in MapReduce framework in order to process large scale microblogs with high scalability. Furthermore, we apply a performance model to optimize the execution time by tuning the number of mappers and reducers. Experimental results on actual dataset show MB-LDA outperforms the baseline of LDA and distributed MB-LDA offers an effective solution to topic mining for large scale microblogs.
A systematic review of risk factors for death in adults during and after tuberculosis treatment.

BACKGROUND Despite effective anti-tuberculosis chemotherapy, case-fatality rates of up to 25% are described in both industrialised and resource-poor settings. An understanding of the factors predisposing to poor outcome may allow the development of adjunctive treatment strategies or closer clinical monitoring in high-risk individuals. OBJECTIVES To describe the definitions and timing of deaths due to tuberculosis (TB), and the reported range of risk factors for death. METHODS All electronically available studies investigating risk factors for death in TB patients from 1966 to 2010 were analysed. Included were peer-reviewed reports of cohort, case control or cross-sectional studies with the primary objective of determination of quantitative effect estimates of the relationship between risk factors and death in adults treated for TB. Many studies were limited by their retrospective design, reliance on data from registries and charts, and risk of reporting bias. RESULTS Most studies reported risk factors for all-cause mortality throughout anti-tuberculosis treatment. In the context of high TB incidence and human immunodeficiency virus (HIV) prevalence, risk factors for death are HIV positivity, advancing immunosuppression, smear-negative disease and malnutrition. In regions of low TB incidence and HIV prevalence, risk factors include non-infective comorbidities, sputum smear-positive disease and alcohol and substance misuse. CONCLUSIONS There remains a need for prospective clinical studies, particularly with a focus on deaths occurring during the first months of anti-tuberculosis treatment. Qualitative research should be used to further explore the relationship between sex and health-seeking behaviour, and to optimise delivery of health care to socially marginalised groups.
Socioeconomic determinants affecting the quality of life among diabetic and hypertensive patients in a rural area, Egypt

Background: Diabetes mellitus and hypertension have a high prevalence of growth in all countries threatening to become a global epidemic risk, thus the quality of life this category of patients is extremely important. The aim of this study was to assess the socioeconomic determinants affecting the quality of life among diabetic and hypertensive patients. Patient and Methods: A descriptive cross-sectional study was conducted in a rural family health care center in El-Batanon village, in the delta region of Menoufia, Egypt. The recruited sample population was 401 participants over six month's context time frame (diabetic and hypertensive participants were 224 and 117 respectively). All participants were interviewed using a questionnaire to assess the demographic characteristics, socioeconomic status, type, duration and treatments of illness and the 36-Item Short Form Health Survey. Results: Patients with Diabetes presented a poorer health related quality of life than those with hypertension in perceived health in the areas of role-physical (RP) (P < 0.05), bodily pain (BP) (P < 0.001), general health (GH) (P < 0.05), vitality (VT) (P < 0.05), social functioning (SF) (P < 0.001) and role-emotional (RE) (P < 0.001). Age, Sex, Family size, socioeconomic score and occupation were the main Socioeconomic Determinants affecting the quality of life among diabetic and hypertensive patients. Conclusion: Diabetes and hypertension seem to comparably impair the health-related quality of life. There is a need to develop and implement effective targeted intervention to help the patients to cope with their life in a better way.
A combination of HER‐2 status and the St. Gallen classification provides useful information on prognosis in lymph node‐negative breast carcinoma

Adjuvant chemotherapy for patients with lymph node‐negative breast carcinoma is being recommended currently based on the St. Gallen classification. The prognostic importance of HER‐2 status in patients with lymph node‐negative breast carcinoma has been investigated extensively, with contradictory results. The authors investigated the clinical relevance of HER‐2 overexpression when combined with the St. Gallen classification in lymph node‐negative breast carcinoma.
Kaposi's sarcoma-associated herpesvirus-specific immune reconstitution and antiviral effect of combined HAART/chemotherapy in HIV clade C-infected individuals with Kaposi's sarcoma

Background:Kaposi's sarcoma-associated herpesvirus (KSHV) is endemic in South Africa and the clinical manifestation of AIDS-associated Kaposi's sarcoma (KS) represents a significant clinical problem. Whereas the positive effects of HAART on the regression of KS have been well established, less is known about the role of herpesvirus-specific cellular immunity in disease improvement. Design:Thirty-three treatment-naive HIV clade C-infected individuals with KS were randomly assigned into two treatment arms (HAART plus systemic chemotherapy versus HAART alone). KSHV-specific cellular immune responses, viral loads and clinical outcome were evaluated. Methods:KSHV, Epstein–Barr virus and HIV-specific cellular immunity was measured using an IFN-γ enzyme-linked immunospot assay in samples obtained at baseline and up to 11 months after treatment initiation. Cell-associated KSHV viremia was determined by real-time polymerase chain reaction. Results:Robust increases in CD4 cell counts and suppressed HIV viral loads were seen in parallel with significant increases in the KSHV-specific cellular immune responses over time. Although slowly increasing after 5 months, KSHV-specific T-cell responses were significantly elevated only after 11 months, with both lytic and latent antigens being more frequently targeted. A trend towards better clinical outcome with HAART plus chemotherapy treatment was observed compared with HAART alone, and was accompanied by a significant reduction in cellular KSHV viral load in the HAART plus chemotherapy-treated subjects but not those treated with HAART alone after 11 months of treatment. Conclusion:The data show a temporal association between the clinical improvement of KS and the re-appearance of KSHV-specific cellular immunity, and demonstrate an effective suppression of KSHV viral replication using combination therapy.
Solution Structure and In Silico Binding of a Cyclic Peptide with Hepatitis B Surface Antigen

A specific ligand targeting the immunodominant region of hepatitis B virus is desired in neutralizing the infectivity of the virus. In a previous study, a disulfide constrained cyclic peptide cyclo S1,S9 Cys‐Glu‐Thr‐Gly‐Ala‐Lys‐Pro‐His‐Cys (S1, S9‐cyclo‐CETGAKPHC) was isolated from a phage displayed cyclic peptide library using an affinity selection method against hepatitis B surface antigen. The cyclic peptide binds tightly to hepatitis B surface antigen with a relative dissociation constant (KDrel) of 2.9 nm. The binding site of the peptide was located at the immunodominant region on hepatitis B surface antigen. Consequently, this study was aimed to elucidate the structure of the cyclic peptide and its interaction with hepatitis B surface antigen in silico. The solution structure of this cyclic peptide was solved using 1H, 13C, and 15N NMR spectroscopy and molecular dynamics simulations with NMR‐derived distance and torsion angle restraints. The cyclic peptide adopted two distinct conformations due to the isomerization of the Pro residue with one structured region in the ETGA sequence. Docking studies of the peptide ensemble with a model structure of hepatitis B surface antigen revealed that the cyclic peptide can potentially be developed as a therapeutic drug that inhibits the virus–host interactions.
RBP-L, a transcription factor related to RBP-Jkappa

RBP-Jkappa is a sequence-specific DNA binding protein which plays a central role in signalling downstream of the Notch receptor by physically interacting with its intracellular region. Although at least four Notch genes exist in mammals, it is unknown whether each Notch requires a specific downstream signalling molecule. Here we report isolation and characterization of a mouse RBP-Jkappa-related gene named RBP-L that is expressed almost exclusively in lung, in contrast to the ubiquitous expression of RBP-Jkappa. For simplicity, we propose to call RBP-Jkappa RBP-J. The RBP-L protein bound to a DNA sequence almost identical to that of RBP-J. Surprisingly, RBP-L did not interact with any of the known four mouse Notch proteins. Although we found that RBP-L and EBNA-2 cooperated in transcriptional activation, they did not show significantly strong protein-protein interaction that can be detected by several in vivo and in vitro assays. This is again in contrast to physical association of RBP-J with EBNA-2. Several models to explain functional interaction between RBP-L and EBNA-2 are discussed.
Rofecoxib, as a safe alternative for acetyl salicylic acid/nonsteroidal anti-inflammatory drug-intolerant patients.

BACKGROUND Intolerance to acetylsalicylic acid (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs) is a crucial problem in medical practice. There is therefore a need for safer NSAIDs in analgesic-intolerant patients. OBJECTIVE To assess the safety of rofecoxib, a selective COX-2 inhibitor, in ASA/NSAID-intolerant patients. METHODS A single blind, placebo-controlled oral challenge procedure was applied to 94 adult patients (M/F: 30/64, mean age: 39.2 +/- 11.9 yrs) with a reliable history of ASA/NSAID intolerance. 1/4 and 3/4 divided doses of placebo and rofecoxib were given with 2-hour intervals on consecutive days. During the challenge procedure, blood pressure, heart rate, nasoocular, pulmonary and cutaneous symptoms were monitored. Erythema, pruritus accompanied by erythema, urticaria/angioedema, rhinorrea, nasal obstruction, sneezing, dyspnea or cough associated with a decrease of at least 20% in the FEV1, and hypotension were considered as positive reactions. RESULTS None of the patients reacted to placebo. Only one patient (1.1%) presented urticarial-type cutaneous reaction to rofecoxib challenge. The remaining patients (98.9%) perfectly tolerated the drug challenge. CONCLUSION Rofecoxib can be used as a safe alternative drug for ASA/NSAID intolerant patients.
Overexertion Injuries in Home Health Care Workers and the Need for Ergonomics

ABSTRACT Home health care workers have high rates of back injuries and other musculoskeletal problems. This article addresses issues surrounding work-related overexertion injuries in home health care workers, including summaries of relevant research on workers in home settings as well as in traditional health care settings such as hospitals and nursing homes. The main work factors associated with these injuries are forceful exertions and awkward postures during patient- care tasks, especially while lifting and moving patients. Ergonomics–the design of work tasks to best accommodate natural human capabilities–is the most promising approach for preventing injuries, and for enhancing the comfort and safety of workers and patients.