Miracle-dz/UniFAR-FTUs huggingface dataset:
Moderate Physical Training Attenuates the Effects of Perinatal Undernutrition on the Morphometry of the Splenic Lymphoid Follicles in Endotoxemic Adult Rats

Background/Aims: Physical training is a well-known inducer of positive physiological adaptations. The effects of moderate physical training on the morphometry of splenic lymphoid follicles of endotoxemic rats submitted to a perinatal low-protein (LP) diet were evaluated. Methods: Male Wistar rats were divided into two groups according to their mother’s diet (17% casein, control, C) and, undernourished (8% casein, LP diet). On postnatal day 63, the animals were submitted to moderate physical training (8 weeks, 5 days·week–1, 60 min·day–1, at 70% of VO2max). After the physical training period, half of each group received an injection of either lipopolysaccharide (LPS) or saline. Plasma corticosterone concentration, blood differential leukocyte counts and splenic morphometric parameters were analyzed. Results: In undernourished toxemic (LP + LPS), LPS increased plasma corticosterone concentrations, but not in previously trained (LP + T + LPS) animals. Neutrophilia and lymphopenia in response to LPS was more pronounced in pups from undernourished mothers (LP + LPS). LP + LPS animals showed a higher increment (47.4%) in the number of lymphoid follicles, a reduction in the number and size of the splenic follicles, and in the marginal zone area. Those alterations were attenuated in trained animals (LP + T + LPS). Conclusions: Physical training attenuates the effects of nutritional programming on the splenic microanatomy by a mechanism that involves the hypothalamic-pituitary-adrenal axis.
Stereotactic radiosurgery with concurrent lapatinib is associated with improved local control for HER2-positive breast cancer brain metastases.

OBJECTIVEWith increasing survival for patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer in the trastuzumab era, there is an increased risk of brain metastasis. Therefore, there is interest in optimizing intracranial disease control. Lapatinib is a small-molecule dual HER2/epidermal growth factor receptor inhibitor that has demonstrated intracranial activity against HER2+ breast cancer brain metastases. The objective of this study was to investigate the impact of lapatinib combined with stereotactic radiosurgery (SRS) on local control of brain metastases.METHODSPatients with HER2+ breast cancer brain metastases who underwent SRS from 1997-2015 were included. The primary outcome was the cumulative incidence of local failure following SRS. Secondary outcomes included the cumulative incidence of radiation necrosis and overall survival.RESULTSOne hundred twenty-six patients with HER2+ breast cancer who underwent SRS to 479 brain metastases (median 5 lesions per patient) were included. Among these, 75 patients had luminal B subtype (hormone receptor-positive, HER2+) and 51 patients had HER2-enriched histology (hormone receptor-negative, HER2+). Forty-seven patients received lapatinib during the course of their disease, of whom 24 received concurrent lapatinib with SRS. The median radiographic follow-up among all patients was 17.1 months. Concurrent lapatinib was associated with reduction in local failure at 12 months (5.7% vs 15.1%, p < 0.01). For lesions in the ≤ 75th percentile by volume, concurrent lapatinib significantly decreased local failure. However, for lesions in the > 75th percentile (> 1.10 cm3), concurrent lapatinib did not significantly improve local failure. Any use of lapatinib after development of brain metastasis improved median survival compared to SRS without lapatinib (27.3 vs 19.5 months, p = 0.03). The 12-month risk of radiation necrosis was consistently lower in the lapatinib cohort compared to the SRS-alone cohort (1.3% vs 6.3%, p < 0.01), despite extended survival.CONCLUSIONSFor patients with HER2+ breast cancer brain metastases, the use of lapatinib concurrently with SRS improved local control of brain metastases, without an increased rate of radiation necrosis. Concurrent lapatinib best augments the efficacy of SRS for lesions ≤ 1.10 cm3 in volume. In patients who underwent SRS for HER2+ breast cancer brain metastases, the use of lapatinib at any time point in the therapy course was associated with a survival benefit. The use of lapatinib combined with radiosurgery warrants further prospective evaluation.
Progressing rehabilitation after injury: consider the ‘control-chaos continuum’

Early reintegration to training and match play following injury increases the risk of reinjury. However, having key players available benefits the team.1 Practitioners must balance these two components of the return to sport (RTS) process, combining evidence and clinical experience to estimate this risk, then plan and adapt RTS accordingly.1 Quantifying and monitoring training load is key in guiding this process while managing reinjury risk,2–4 and global positioning systems (GPS) provide a valid measure of external running loads.5 However, as practitioners, we should focus on both quantitative aspects of running load progression and qualitative characteristics of movement in competition. This includes highly variable, spontaneous and unanticipated movements (the conditions of ‘chaos’) reflecting the unpredictable nature of the sport. In this editorial, we present the ‘control-chaos continuum’ (CCC) (figure 1), interlinking GPS variables, while progressively incorporating greater perceptual and reactive neurocognitive challenges.6 7 This framework moves from high control to high chaos, and is based on more than a decade of rehabilitation and RTS in the demanding setting of English Premier League football. Figure 1 Return to sport framework - the control-chaos continuum. Control=high level of structure on behaviour/actions/movement, that is, controlled situation. Chaos=unpredictable behaviour/actions/movement, as to appear random/reactive, that is, chaotic situation. Green represents high control (low intensity) moving towards high chaos (high intensity). Model can be adjusted according to specific injury diagnosis, estimated tissue healing times and expected return to training. Acc/Dec Magnitude =rate of change in velocity, for example, 3 ms−2. **Game load adjustable dependent on injury type/severity. ACC, accelerations; BW, bodyweight; COD, change of direction; DEC, decelerations; Exp-D, explosive distance (accelerating/decelerating from 2 to 4 ms−1 5.5 ms−1); MS, maximal speed; MAXHR, maximal heart rate; PR, passive recovery; SPR, sprint distance (>7 ms−1); TD, total distance. Using retrospective player chronic running loads (GPS) in …
Review article: managing the adverse events caused by anti‐TNF therapy in inflammatory bowel disease

Biological therapy is currently widely used to treat IBD. Infliximab, adalimumab and golimumab are currently licensed anti‐TNF therapies. Biosimilar anti‐TNF monoclonal antibodies are increasingly used. Anti‐TNF therapies are widely used and their adverse effects are well characterised, and may cause significant morbidity and mortality in a small proportion of exposed patients. Gastroenterologists need to understand the mechanisms for these effects, recognise these swiftly and manage such events appropriately.
Inflammasome Signaling and Impaired Vascular Health in Psoriasis

Objective— Psoriasis is an inflammatory skin disease which heightens the risk of cardiovascular disease. This study directly investigated vascular endothelial health and systemically altered pathways in psoriasis and matched controls. Approach and Results— Twenty patients (mean age, 40 years; 50% male) with active psoriasis and 10 age-, sex-matched controls were recruited. To investigate systemically alerted pathways, a deep sequencing omics approach was applied, including unbiased blood transcriptomic and targeted proteomic analysis. Vascular endothelial health was assessed by transcriptomic profiling of endothelial cells obtained from the brachial veins of recruited participants. Blood transcriptomic profiling identified inflammasome signaling as the highest differentially expressed canonical pathway (Z score 1.6; P=1×10-7) including upregulation of CASP5 and interleukin (IL)-1&bgr;. Proteomic panels revealed IL-6 as a top differentially expressed cytokine in psoriasis with pathway analysis highlighting IL-1&bgr; (Z score 3.7; P=1.02×10-23) as an upstream activator of the observed upregulated proteins. Direct profiling of harvested brachial vein endothelial cells demonstrated inflammatory transcript (eg, IL-1&bgr;, CXCL10, VCAM-1, IL-8, CXCL1, Lymphotoxin beta, ICAM-1, COX-2, and CCL3) upregulation between psoriasis versus controls. A linear relationship was seen between differentially expressed endothelial inflammatory transcripts and psoriasis disease severity. IL-6 levels correlated with inflammatory endothelial cell transcripts and whole blood inflammasome-associated transcripts, including CASP5 and IL-1&bgr;. Conclusions— An unbiased sequencing approach demonstrated the inflammasome as the most differentially altered pathway in psoriasis versus controls. Inflammasome signaling correlated with psoriasis disease severity, circulating IL-6, and proinflammatory endothelial transcripts. These findings help better explain the heightened risk of cardiovascular disease in psoriasis. Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT03228017.
Serum fetuin-A is associated with the components of MIAC(malnutrition, inflammation, atherosclerosis, calcification) syndrome in different stages of chronic kidney disease

Background/aim Fetuin-A, a circulating inhibitor of calcification, is a marker of inflammatory-nutritional state. We evaluated the association between serum fetuin-A levels and vascular calcification, intima-media thickness, and nutritional and inflammatory markers in different stages of chronic kidney disease (CKD). Materials and methods CKD patients were sampled for calcium-phosphate parameters and nutritional and inflammatory markers [highly sensitive C-reactive protein (hs-CRP)], and serum fetuin-A levels. Intima-media thicknesses of the common carotid arteries (CIMT) were measured. Peripheral artery calcification scores were obtained. Results A total of 238 patients were included in the study. Fetuin-A levels in patients with end-stage renal disease were significantly lower than those in patients with stage-3 and stage-4 CKD (stage-5 vs. stage-4, P < 0.001; stage-5 vs. stage-3, P < 0.001). Fetuin-A was negatively correlated with creatinine (P < 0.001), Ca × P product (P < 0.001), hs-CRP (P = 0.01), vascular calcification score (P < 0.001), and CIMT (P < 0.001), and positively correlated with BMI (P < 0.001, r = 0.30) and serum albumin (P < 0.001). Conclusion Lower levels of fetuin-A were associated with higher vascular calcification scores, CIMT, hs-CRP levels, and lower BMI and albumin. Fetuin-A deficiency may be a key element for MIAC syndrome.
Learning new relational categories by children with autism spectrum disorders, children with typical development and children with intellectual disabilities: effects of comparison and familiarity on systematicity.

BACKGROUND Systematicity principle, used during analogical reasoning, enables building up deeper abstract concepts as part of structure mapping. The purpose of this study was to investigate structure mapping processes that occur during acquisition of new relational categories and to identify the learning patterns and systematicity of children with autism spectrum disorder (ASD) compared with intellectual and developmental disabilities (IDD) and typical development (TD). Comparison effect and level of familiarity were used to investigate structural mapping processes. METHODS Three groups of 24 children participated in the study. Using a computer program, participants were asked to select a perceptual or relational choice based on one or two standards using illustrations depicting new relational categories in various spatial configurations. Known, partially known and unknown illustrations were used in depicting three levels of familiarity. RESULTS All three groups selected perceptual choices when one standard was available (no comparison). However, when two standards were available, enabling a comparison, children with IDD and TD increased their tendency for selecting abstract relational categories, while children with ASD did not change their preference and continued selecting perceptual choices. Level of familiarity increased selection of relational choices among children with TD and IDD but not among children with ASD. CONCLUSIONS Systematicity principle was evident mostly in the selection of relational choices by children with TD and IDD when the illustrations were known or partially known. Hence, even when an opportunity to compare and to use previously known information was available, structure mapping processes and systematicity were implemented to align information among children TD and IDD but failed to assist the learning of new relational categories among children with ASD.
Accuracy of the α-defensin lateral flow assay for diagnosing periprosthetic joint infection in Asians

Objective: This study aimed to test the accuracy of the Synovasure®, α-defensin lateral flow test kit, in diagnosing periprosthetic joint infections (PJIs) in a predominantly Asian population and to evaluate whether other patient or disease factors may affect its results. Methods: 61 Asian patients comprising 70 hip or knee prosthetic joints, performed between November 2015 and November 2018, were retrospectively evaluated. Cases were categorized as infected or not infected using Musculoskeletal Infection Society (MSIS) Criteria. Synovial fluid was tested for α-defensin using a commercially available kit. Results: The Synovasure test had a sensitivity of 73.7% (95% confidence interval (CI): 48.8–90.9%) and specificity of 92.2% (95% CI: 81.1–97.8%) in an Asian population, which was slightly lower compared to previously reported studies in a predominantly Caucasian population. The positive predictive value was 77.8% (95% CI: 56.8–90.3%) and the negative predictive value was 90.4% (95% CI: 81.5–95.2%). The test had an area under curve (AUC) of the receiver operating characteristic (ROC) graph of 0.938, which represents an accuracy that is similar to synovial white blood cells (WBCs) and almost equivalent to that of synovial polymorphonuclear cells (PMNs). The presence of diabetes (p = 0.26), systemic inflammatory joint disease (p = 0.33), other metallic implants (p = 0.53), immunosuppression (p = 0.13), prior antibiotic usage (p = 0.99), and chronicity of symptoms (p = 0.34) was not significantly associated with a positive test in patients with PJI. Conclusion: The α-defensin lateral flow test kit is highly accurate in the diagnosis of PJI but with slightly lower sensitivity and specificity in an Asian population when compared with previous studies. The test should be used in conjunction with other MSIS criteria to provide clinically relevant and meaningful results for the diagnosis of PJI.
Greenness and Depression Incidence among Older Women

Background: Recent evidence suggests that higher levels of residential greenness may contribute to better mental health. Despite this, few studies have considered its impact on depression, and most are cross-sectional. Objective: The objective of this study was to examine surrounding residential greenness and depression risk prospectively in the Nurses’ Health Study. Methods: A total of 38,947 women (mean age throughout follow-up 70 y [range 54–91 y]) without depression in 2000 were followed to 2010. Residential greenness was measured using the satellite-based Normalized Difference Vegetation Index (NDVI) and defined as the mean greenness value within 250-m and 1,250-m radii of the women’s residences in July of each year. Incidence of depression was defined according to the first self-report of either physician-diagnosed depression or regular antidepressant use. We used Cox proportional hazards models to examine the relationship between greenness and depression incidence and assessed physical activity as a potential effect modifier and mediator. Results: Over 315,548 person-years, 3,612 incident depression cases occurred. In multivariable-adjusted models, living in the highest quintile of residential greenness within 250m was associated with a 13% reduction in depression risk (HR=0.87 [95% confidence interval (CI): 0.78, 0.98]) compared with the lowest quintile. The association between greenness and depression did not appear to be mediated by physical activity, nor was there evidence of effect modification by physical activity. Conclusions: In this population of mostly white women, we estimated an inverse association between the highest level of surrounding summer greenness and the risk of self-reported depression. https://doi.org/10.1289/EHP1229
A Framework for the Evaluation of Digital Musical Instruments

At the outset of a discussion of evaluating digital musical instruments (DMIs)—that is to say, instruments whose sound generators are digital and separable (though not necessarily separate) from their control interfaces (Malloch et al. 2006)—it is reasonable to ask what the term evaluation in this context really means. After all, there may be many perspectives from which to view the effectiveness of the instruments we build. For most performers, performance on an instrument becomes a means of evaluating how well it functions in the context of live music making, and their measure of success is the response of the audience to their performance. Audiences evaluate performances on the basis of how engaged they feel by what they have seen and heard. When questioned, they are likely to describe good performances as “exciting,” “skillful,” “musical. ” Bad performances are “boring,” and those which are marred by technical malfunction are often dismissed out of hand. If performance is considered to be a valid means of evaluating a musical instrument, then it follows that, for the field of DMI design, a much broader definition of the term “evaluation” than that typically used in human–computer interaction (HCI) is required to reflect the fact that there are a number of stakeholders involved in the design and evaluation of DMIs. In addition to players and audiences, there are also composers, instrument builders, component manufacturers, and perhaps even customers. And each of these stakeholders may have a different concept of what is meant by “evaluation. ” Composers, for example, may evaluate an instrument in terms of how reliable it is. If a composer writes a piece of instrumental music to be performed on a DMI, then they ought to be able to assume that (1) the instrumentalist is skilled on their instrument, and (2) the instrument has a known space of sound attributes that the composer can draw upon for musical effect.
The clinical implication of CD45RA+ naïve T cells and CD45RO+ memory T cells in advanced pancreatic cancer: a proxy for tumor biology and outcome prediction

Naïve and memory T cells play a pivotal role in solid tumor pathogenesis but their role in pancreatic cancer progression remains elusive. Thus, we aimed to investigate their clinical potential in advanced pancreatic cancer (APC). Flow cytometry was performed to evaluate the level of baseline peripheral naïve and memory T cells from 137 APC patients before receiving first‐line chemotherapy. Interrelationships between naïve, memory T cells and clinicopathological variables were evaluated using Pearson’s correlation. The prognostic impact of naïve and memory T cells were assessed by Kaplan‐Meier analysis and Cox regression. The correlation between naïve/memory T cells and tumor progression was investigated by Student’s t test. CD4+ naïve/memory ratio showed close correlations with hemoglobin, red blood cell (RBC), absolute neutrophil count (ANC) and platelet while CD8+ naïve/memory ratio was correlated with hemoglobin, RBC and CEA. Higher baseline lever of CD4+CD45RO+/CD4+ was correlated with better overall survival (OS) (P = 0.036). Patients with CD4+ naïve/memory ratio ≥0.36 had a poorer OS than those with CD4+ naïve/memory ratio <0.36 (P = 0.021). In addition, CD4+ naïve/memory ratio showed independent prognostic impact (HR 1.427, 95% CI 1.033‐1.973, P = 0.031). Furthermore, poorer clinical response was correlated with higher level of CD8+ naïve/memory ratio after the third cycle of chemotherapy (P = 0.01). Besides, patients with a lower level of CD8+ naïve/memory ratio had longer progression‐free survival (PFS) (P = 0.028). We propose CD4+ naïve/memory ratio as a novel prognostic biomarker for APC. In addition, CD8+ naïve/memory ratio can be a candidate marker for predicting PFS and the change of its level may reflect the progression of APC.
Enhancing Epidemiology Capacity During the 2014-15 West Africa Ebola Outbreak: An Assessment of the Role of Applied Public Health Epidemiologists

Context: In late 2014, the Centers for Disease Control and Prevention requested the support of the Council of State and Territorial Epidemiologists to enhance epidemiologic capacity in the West African countries impacted or threatened by an outbreak of Ebola virus disease. In response, the Council of State and Territorial Epidemiologists recruited 36 senior epidemiologists who, collectively, made 45 deployments to West Africa, averaging 42 days each. Objective: To assess the self-reported experiences and contributions of the deployed epidemiologists, as well as the role of nonprofit public health organizations in large-scale emergency response. Design: Electronic assessment of the deployed epidemiologists. Participants: Experienced applied public health epidemiologists who volunteered to participate in the response to the West Africa Ebola virus disease emergency. Main Outcome Measures: Descriptive data. Results: The chief, reported functional contributions made during deployments include improving surveillance processes (reported by 73.3% of respondents), building meaningful relationships to facilitate response activities (66.7%), improving data quality (53.3%), and improving understanding of the disease/outbreak (40.0%). Among the professional benefits of deployment to West Africa to assist with Ebola virus disease outbreak response are stimulating enthusiasm for public health work (93.3%, n = 30), broadened perspective of global health (86.7%), and sharpened epidemiological skills (56.7%). Conclusions: Owing to their ability to access experienced, senior professionals, the Council of State and Territorial Epidemiologists and other nonprofit public health associations can play a meaningful role boosting surge capacity in a sustained, large-scale emergency response.