Miracle-dz/UniFAR-FTUs huggingface dataset:
Blocking IL-1β reverses the immunosuppression in mouse breast cancer and synergizes with anti–PD-1 for tumor abrogation

Significance Inflammation and immunosuppression are dominant features of cancer progression. In the tumor microenvironment, macrophages produce interleukin-1β (IL-1β), which subsequently recruits myeloid cells from the bone marrow. In mice deficient in IL-1β or in wild-type mice treated with anti–IL-1β Abs, implanted breast cancer tumors regress. Regression is due to decreased tumor-related immunosuppression, meditated mainly by macrophages, and increased antitumor immunity, mediated by elevated dendritic cell function and activated cytotoxic CD8 lymphocytes. Although anti–PD-1 reduces tumor growth, the combination of anti–IL-1β plus anti–PD-1 abrogated the tumors completely. These observations support clinical trials of blocking IL-1β in cancer and that anti–IL-1β is a checkpoint inhibitor. Interleukin-1β (IL-1β) is abundant in the tumor microenvironment, where this cytokine can promote tumor growth, but also antitumor activities. We studied IL-1β during early tumor progression using a model of orthotopically introduced 4T1 breast cancer cells. Whereas there is tumor progression and spontaneous metastasis in wild-type (WT) mice, in IL-1β–deficient mice, tumors begin to grow but subsequently regress. This change is due to recruitment and differentiation of inflammatory monocytes in the tumor microenvironment. In WT mice, macrophages heavily infiltrate tumors, but in IL-1β–deficient mice, low levels of the chemokine CCL2 hamper recruitment of monocytes and, together with low levels of colony-stimulating factor-1 (CSF-1), inhibit their differentiation into macrophages. The low levels of macrophages in IL-1β–deficient mice result in a relatively high percentage of CD11b+ dendritic cells (DCs) in the tumors. In WT mice, IL-10 secretion from macrophages is dominant and induces immunosuppression and tumor progression; in contrast, in IL-1β–deficient mice, IL-12 secretion by CD11b+ DCs prevails and supports antitumor immunity. The antitumor immunity in IL-1β–deficient mice includes activated CD8+ lymphocytes expressing IFN-γ, TNF-α, and granzyme B; these cells infiltrate tumors and induce regression. WT mice with 4T1 tumors were treated with either anti–IL-1β or anti–PD-1 Abs, each of which resulted in partial growth inhibition. However, treating mice first with anti–IL-1β Abs followed by anti–PD-1 Abs completely abrogated tumor progression. These data define microenvironmental IL-1β as a master cytokine in tumor progression. In addition to reducing tumor progression, blocking IL-1β facilitates checkpoint inhibition.
Development and Psychometric Evaluation of a Brief Approach and Avoidance of Alcohol Questionnaire

BACKGROUND The Approach and Avoidance of Alcohol Questionnaire (AAAQ) was developed as a measure of craving to assess both desires to consume and desires to avoid consuming alcohol. Although the measure has been used in a variety of populations to predict future alcohol use behavior, the factor structures observed vary based on sample type (e.g., clinical vs. college samples) and may be overly long for use in repeated measures designs. The current article describes the development of a brief version of the AAAQ for use in clinical populations. METHODS Using existing data sets of individuals in treatment for alcohol use disorder, exploratory analyses (e.g., exploratory factor analysis and item response theory) were conducted using an inpatient sample (N = 298) at a substance abuse treatment facility. Confirmatory analyses (e.g., confirmatory factor analysis and multiple regression) were conducted using an inpatient detoxification sample (N = 175) and a longitudinal outpatient treatment sample (N = 53). RESULTS The brief AAAQ had comparable internal consistency, explained a similar amount of variance in alcohol consumption and related problems, and exhibited superior model fit as compared to the original measure. CONCLUSIONS These findings indicate that the brief AAAQ is an effective tool to assess alcohol craving in clinical populations in treatment settings.
Editorial on: "Superion® InterSpinous Spacer Treatment of Moderate Spinal Stenosis: 4-year Results".

Nunley et al . must be commended for the effort they are currently putting in following-up, since 5 years by now, a cohort of patients treated with Superion implant (1). Originally, the study compared the results of this device with those of the X-Stop. Due to the recall of the X-Stop from the market and the unavailability of patients treated with this device, the authors were obliged to present the data about the Superion without any control.
The implementation of workplace based assessment in the context of clinical radiology training

Workplace based assessment (WPBA) was introduced into clinical radiology training in 2010. The purpose of the study was to investigate its implementation by addressing research questions concerning the assessments’ day-to-day realisation, the participants’ influence upon their enactment, and the utility of the process. The prior history of the introduction of WPBA into postgraduate medical training and the Royal College of Radiologists’ guidance regarding the assessments’ usage served as reference points for the study findings. Semi-structured interviews were undertaken with 20 radiologists (12 trainers, 8 trainees) in order to discover their opinions of the implementation and usage of WPBA in radiology. The interview data were subjected to thematic analysis in order to identify issues of importance to interviewees, address the research questions and suggest any means of improving the assessments. The analysis showed that most interviewees thought that WPBA had a formative purpose, as per central guidance, although some assessors felt it could be used summatively in certain circumstances. The day to day realisation of the assessments was subject to some variation, and although this might be seen as inevitable due to differing circumstances, there was evidence of both trainees and trainers manipulating the process to suit their own purposes. There was also evidence of some trainers frankly adapting the assessments’ usage depending upon trainees’ seniority or time in an attachment. Interviewees described various weaknesses of the process, including the peremptory nature of some assessments, failure to identify underperforming trainees and poor assessor preparedness when WPBA was introduced. Reference to published literature from other postgraduate medical specialties showed that many of these problems were generic in nature, rather than confined to radiology. Suggested means by which WPBA could be improved included joint trainee and trainer leadership of the process, better training of assessors and refinement of the assessments themselves.
Hypoglossal nerve stimulation in three adults with down syndrome and severe obstructive sleep apnea

We present three adults with Down syndrome and obstructive sleep apnea (OSA) treated with hypoglossal nerve stimulation. The average age of these three males was 37.3 years. All patients had severe OSA on polysomnography. Postimplantation titration sleep studies exhibited residual OSA according to average total apnea‐hypopnea index (AHI), but there were significant reductions (86%–100%) in the titrated AHI at the ideal device setting. Morbidity of the surgery was low, and there was excellent device adherence, with an average of 57.3 hours/week. All patients reported subjective improvements in symptoms, and one patient experienced improved blood sugar control.
IL-12 Gene Electrotransfer Triggers a Change in Immune Response within Mouse Tumors

Metastatic melanoma is an aggressive skin cancer with a relatively low survival rate. Immune-based therapies have shown promise in the treatment of melanoma, but overall complete response rates are still low. Previous studies have demonstrated the potential of plasmid IL-12 (pIL-12) delivered by gene electrotransfer (GET) to be an effective immunotherapy for melanoma. However, events occurring in the tumor microenvironment following delivery have not been delineated. Therefore, utilizing a B16F10 mouse melanoma model, we evaluated changes in the tumor microenvironment following delivery of pIL-12 using different GET parameters or injection of plasmid alone. The results revealed a unique immune cell composition after intratumoral injection of pIL-12 GET. The number of immune memory cells was markedly increased in pIL-12 GET melanoma groups compared to control group. This was validated using flow cytometry to analyze peripheral blood mononuclear cells as well as delineating immune cell content using immunohistochemistry. Significant differences in multiple cell types were observed, including CD8+ T cells, regulatory T cells and myeloid cells, which were induced to mount a CD8+PD1− T cells immune response. Taken together, these findings suggest a basic understanding of the sequence of immune activity following pIL-12 GET and also illuminates that adjuvant immunotherapy can have a positive influence on the host immune response to cancer.
Impact of cancer service centralisation on the radical treatment of men with high‐risk and locally advanced prostate cancer: A national cross‐sectional analysis in England

In many countries, specialist cancer services are centralised to improve outcomes. We explored how centralisation affects the radical treatment of high‐risk and locally advanced prostate cancer in the English NHS. 79,085 patients diagnosed with high‐risk and locally advanced prostate cancer in England (April 2014 to March 2016) were identified in the National Prostate Cancer Audit database. Poisson models were used to estimate risk ratios (RR) for undergoing radical treatment by whether men were diagnosed at a regional co‐ordinating centre (‘hub’), for having surgery by the presence of surgical services on‐site, and for receiving high dose‐rate brachytherapy (HDR‐BT) in addition to external beam radiotherapy by its regional availability. Men were equally likely to receive radical treatment, irrespective of whether they were diagnosed in a hub (RR 0.99, 95% CI 0.91–1.08). Men were more likely to have surgery if they were diagnosed at a hospital with surgical services on site (RR 1.24, 1.10–1.40), and more likely to receive additional HDR‐BT if they were diagnosed at a hospital with direct regional access to this service (RR 6.16, 2.94–12.92). Centralisation of specialist cancer services does not affect whether men receive radical treatment, but it does affect treatment modality. Centralisation may have a negative impact on access to specific treatment modalities.
Splenic conservation in children with splenic injury at Nnewi - South Eastern Nigeria: a ten year audit

Background : The spleen is commonest organ injured in blunt abdominal trauma both in adults and in children. With increasing sophistication and modern means of transportation: the number of children sustaining blunt injury to the abdomen is increasing. Hitherto, the mode of treatment has been towards resuscitation and splenectomy but over the past one and half decades, the trend moved to conserve. Objective : We therefore review the management of splenic injuries in children over the past ten years as well as highlight management problems. Patients and Methods : Case notes of all splenic injuries of patients aged 15 yrs and below from 1 st July 1992 to 30 th June 2002 were reviewed. Parameters analysed were; age, sex, mode of injury, grade of surgeon; mode of treatment and outcome of treatment. Results : There were 23 cases; 14 males and 9 females. Seven had grade 1-2 injuries while 16 had grades 3-5 injuries. Four had successful conservation therapy. While 15 had, splenectomy and one died before operation. There were three negative laparatomies. Three patients had postoperative wound sepsis and none had postoperative band. One failed conservation had a re-operation and eventual splenectomy. Conclusion : Splenic conservation is feasible in a developing country like ours but the challenges are enormous and problems abound. Improvement of facilities and establishment of peadiatric trauma units will ease mush of the problems. Keywords : splenic, conservation therapy, children Tropical Journal of Medical Research Vol. 9(2) 2005: 14-16
Tarsal Tunnel Mechanosensitivity Is Increased in Patients with Asthma: A Case-Control Study

Background: Based on changes in lung function and musculoskeletal disorders in patients with asthma, this study aimed to compare the tarsal tunnel and fibular bone pressure pain thresholds (PPTs) of patients with asthma and healthy matched-paired controls. Methods: A case-control study was performed. One hundred participants were recruited: 50 asthma patients and 50 healthy matched-paired controls. Bilaterally, tarsal tunnel and fibula bone PPTs were registered. Results: Statistically significant differences (p < 0.01) were shown bilaterally for tarsal tunnel PPT. With the exception of fibula PPT (p > 0.05), asthma patients presented less tarsal tunnel PPT than healthy participants. Statistically significant differences (p < 0.05) were shown for two linear regression prediction models of the right (R2 = 0.279) and left (R2 = 0.249) tarsal tunnels PPTs as dependent variables, and based on sex, group, contralateral tarsal tunnel PPT and ipsilateral fibula PPT as independent variables. Conclusions: The study findings showed that a bilateral tarsal tunnel mechanosensitivity increase is exhibited in patients diagnosed with asthma. The presence of asthma may bilaterally predict the PPT of tarsal tunnel. These findings may suggest the presence of central sensitization in asthma patients, which could clinically predispose them to musculoskeletal disorders, such as tarsal tunnel syndrome.
B cells in esophago-gastric adenocarcinoma are highly differentiated, organize in tertiary lymphoid structures and produce tumor-specific antibodies

ABSTRACT Tumor-infiltrating lymphocytes (TILs) are correlated to prognosis of several kinds of cancer. Most studies focused on T cells, while the role of tumor-associated B cells (TABs) has only recently gained more attention. TABs contain subpopulations with distinct functions, potentially promoting or inhibiting immune responses. This study provides a detailed analysis of TABs in gastro-esophageal adenocarcinoma (EAC). Flow cytometric analyses of single cell suspensions of tumor samples, mucosa, lymph nodes and peripheral blood mononuclear cells (PBMC) of EAC patients and healthy controls revealed a distinct B cell compartment in cancer patients. B cells were increased in tumor samples and subset-analyses of TILs showed increased proportions of differentiated and activated B cells and an enrichment for follicular T helper cells. Confocal microscopy demonstrated that TABs were mainly organized in tertiary lymphoid structures (TLS), which resemble lymphoid follicles in secondary lymphoid organs. A panel of 34 tumor-associated antigens (TAAs) expressed in EAC was identified based on public databases and TCGA data to analyze tumor-specific B cell responses using a LUMINEXTM bead assay and flow cytometry. Structural analyses of TLS and the detection of tumor-specific antibodies against one or more TAAs in 48.1% of analyzed serum samples underline presence of anti-tumor B cell responses in EAC. Interestingly, B cells were decreased in tumors with expression of Programmed Death Ligand 1 or impaired HLA-I expression. These data demonstrate that anti-tumor B cell responses are an additional and underestimated aspect of EAC. Our results are of immediate translational relevance to emerging immunotherapies.
Detecting Texts: The Metaphysical Detective Story from Poe to Postmodernism

Although readers of detective fiction ordinarily expect to learn the mystery's solution at the end, there is another kind of detective story -- whose history encompasses writers as diverse as Poe, Borges, Robbe-Grillet, Auster, and Stephen King -- that ends with a question rather than an answer. The detective not only fails to solve the crime, but also confronts insoluble mysteries of interpretation and identity. As the contributors to Detecting Texts contend, such stories belong to a distinct genre, the metaphysical detective story, in which the detective hero's inability to interpret the mystery inevitably casts doubt on the reader's similar attempt to make sense of the text and the world.
Impact of Commercial Oenotannin and Mannoprotein Products on the Chemical and Sensory Properties of Shiraz Wines Made from Sequentially Harvested Fruit

The tannin and polysaccharide profiles and therefore sensory properties of wine are influenced by fruit maturity at harvest, and practices employed during winemaking. This study investigated the extent to which commercial winemaking supplements (skin and seed tannins, and mannoprotein (MP)) can enhance the mouthfeel properties of red wine, in particular, wine made from grapes harvested before commercial ripeness (early-harvest). Supplements were added to wines made from Shiraz grapes harvested at 20.8 and 24.5 °Brix. The chemical composition and mouthfeel properties of wines were then determined by high performance liquid chromatography and descriptive analysis (DA), respectively. Wines made from riper grapes had higher levels of tannin than wines made from early-harvest grapes, but similar polysaccharide levels were observed. The addition of seed oenotannin yielded higher tannin levels than addition of skin oenotannin, particularly for wines made from early-harvest grapes. The DA panel perceived sensory differences between H1 and H2 wines, but could not perceive any effect of supplementation on wine mouthfeel properties, with the exception of a minor increase in sweetness, attributed to mannoprotein addition to H1 wines, even when MP was added to wines at 2.5 times the level recommended for use in Australia.
Managerial Issues of Enterprise Resource Planning Systems

The primary purpose of this text is to lay out the scope of ERP Systems implementation, explain the competitive advantages of using ERP Systems, and support general concepts with short case studies. This text covers the fundamental issues important in ERP implementation and management, starting from an information systems, information technology project management perspective. Each chapter will include a review of real cases of ERP implementations related to that particular chapter content. The text is meant to be software product independent, in order to enable schools to select their own ERP Systems software tools and use them as time permits. Table of contents Chapter 1: Enterprise Resource Planning SystemsChapter 2: ERP Modules and Historical DevelopmentChapter 3: ERP System Options and Selection MethodsChapter 4: Business Process Reengineering and Best PracticesChapter 5: ERP System InstallationChapter 6: ERP Project ManagementChapter 7: ERP Implementation and MaintenanceChapter 8: Business Intelligence Systems and ERPChapter 9: ERP and Supply ChainsChapter 10: Advanced Technology and ERP SecurityChapter 11: Trends in ERP
Fundamentals of Force-Controlled Friction Riveting: Part II—Joint Global Mechanical Performance and Energy Efficiency

The present work investigates the correlation between energy efficiency and global mechanical performance of hybrid aluminum alloy AA2024 (polyetherimide joints), produced by force-controlled friction riveting. The combinations of parameters followed a central composite design of experiments. Joint formation was correlated with mechanical performance via a volumetric ratio (0.28–0.66 a.u.), with a proposed improvement yielding higher accuracy. Global mechanical performance and ultimate tensile force varied considerably across the range of parameters (1096–9668 N). An energy efficiency threshold was established at 90 J, until which, energy input displayed good linear correlations with volumetric ratio and mechanical performance (R-sq of 0.87 and 0.86, respectively). Additional energy did not significantly contribute toward increasing mechanical performance. Friction parameters (i.e., force and time) displayed the most significant contributions to mechanical performance (32.0% and 21.4%, respectively), given their effects on heat development. For the investigated ranges, forging parameters did not have a significant contribution. A correlation between friction parameters was established to maximize mechanical response while minimizing energy usage. The knowledge from Parts I and II of this investigation allows the production of friction riveted connections in an energy efficient manner and control optimization approach, introduced for the first time in friction riveting.
A systematic review and meta-analysis

Background: Atrial fibrillation (AF) is the most common type of heart arrhythmia, but the impact of long-term, high-intensity endurance exercise on the risk of AF remains uncertain. Methods: PubMed, EMBASE, and Cochrane library databases were searched till Nov 2017 to retrieve the articles. The included studies were summarized, pooled odds ratio (OR) and its 95% confidence interval (CI) were calculated. Both fixed and random effects models were used to combine the data. Stratified and logistic meta-regression analyses were performed to explore the sources of heterogeneity across studies. Results: Nine studies including 2308 athletes and 6593 controls were eligible. Our results showed that the risk of AF was significantly higher in athletes than in general population (OR=2.34, 95% CI=1.04–5.28, Pheterogeneity<.001, I =92.3%). Subgroup analysis based on gender and mean age demonstrated a significantly increased risk in men (OR=4.03, 95% CI=1.73–9.42, Pheterogeneity<.001, I =82.7%) and participants with mean age<60 (OR=3.24, 95%CI=1.23–8.55, Pheterogeneity<.001, I =84.3%). Furthermore, subgroup analysis based on type of athletes demonstrated a significantly increased risk of AF in participants with single type of sport (OR=3.97, 95% CI=1.16–13.62, Pheterogeneity= .018, I =70.4%). Results remained unchanged after performing sensitivity analysis. Meta-regression showed that gender, age, type of study, sample size, and sports mode were unrelated to heterogeneity. Conclusion:Our study confirmed that the risk of AFwas significantly higher in athletes than in general population, especially among men and participants aged <60. Abbreviations: AF = atrial fibrillation, CI = confidence interval, OR = odds ratio, STROBE = Strengthening the Reporting of Observational Studies in Epidemiology.