Miracle-dz/UniFAR-FTUs huggingface dataset:
Dendritic cell and antigen dispersal landscapes regulate T cell immunity

Dendritic cell (DC) subsets with biased capacity for CD4+ and CD8+ T cell activation are asymmetrically distributed in lymph nodes (LNs), but how this affects adaptive responses has not been extensively studied. Here we used quantitative imaging to examine the relationships among antigen dispersal, DC positioning, and T cell activation after protein immunization. Antigens rapidly drained into LNs and formed gradients extending from the lymphatic sinuses, with reduced abundance in the deep LN paracortex. Differential localization of DCs specialized for major histocompatibility complex I (MHC I) and MHC II presentation resulted in preferential activation of CD8+ and CD4+ T cells within distinct LN regions. Because MHC I–specialized DCs are positioned in regions with limited antigen delivery, modest reductions in antigen dose led to a substantially greater decline in CD8+ compared with CD4+ T cell activation, expansion, and clonal diversity. Thus, the collective action of antigen dispersal and DC positioning regulates the extent and quality of T cell immunity, with important implications for vaccine design.
Evaluation of whole‐body MR to CT deformable image registration

Multimodality image registration plays a crucial role in various clinical and research applications. The aim of this study is to present an optimized MR to CT whole‐body deformable image registration algorithm and its validation using clinical studies. A 3D intermodality registration technique based on B‐spline transformation was performed using optimized parameters of the elastix package based on the Insight Toolkit (ITK) framework. Twenty‐eight (17 male and 11 female) clinical studies were used in this work. The registration was evaluated using anatomical landmarks and segmented organs. In addition to 16 anatomical landmarks, three key organs (brain, lungs, and kidneys) and the entire body volume were segmented for evaluation. Several parameters — such as the Euclidean distance between anatomical landmarks, target overlap, Dice and Jaccard coefficients, false positives and false negatives, volume similarity, distance error, and Hausdorff distance — were calculated to quantify the quality of the registration algorithm. Dice coefficients for the majority of patients (>75%) were in the 0.8–1 range for the whole body, brain, and lungs, which satisfies the criteria to achieve excellent alignment. On the other hand, for kidneys, Dice coefficients for volumes of 25% of the patients meet excellent volume agreement requirement, while the majority of patients satisfy good agreement criteria (>0.6). For all patients, the distance error was in 0–10 mm range for all segmented organs. In summary, we optimized and evaluated the accuracy of an MR to CT deformable registration algorithm. The registered images constitute a useful 3D whole‐body MR‐CT atlas suitable for the development and evaluation of novel MR‐guided attenuation correction procedures on hybrid PET‐MR systems. PACS number: 07.05. Pj
Sensitivity of motor adaptation to the statistical properties of an environmental load

SENSITIVITY OF MOTOR ADAPTATION TO THE STATISTICAL PROPERTIES OF AN ENVIRONMENTAL LOAD Timothy M Goetz-Haswell, B.S. Marquette University, 2010 Linear, limited-memory models capture many important features of adaptive motor performance during reaching, stepping and pointing. A recent study in our lab found that a model fitted to data obtained from subjects reaching against elastic loads which varied from trial-to-trial later failed to fit the steady-state response behavior of subjects exposed to deterministic, step changes in load. Does motor adaptation depend on statistical properties of the environment (eg. mean load strength and variability)? Neurologically intact volunteers (n=14) made 6 blocks of 100 planar, ballistic, 10cm, out-and-back reaching movements against spring-like loads having equilibrium positions at the hand’s starting point. View of the limb was not allowed. Load stiffness varied trial-by-trial, and each block of movements differed in mean and/or variance such that three, 3-block contrasts were evaluated: increasing standard deviation (VAR), increasing mean (MEAN), and proportionally increasing standard deviation and mean (WEBER). In the VAR and MEAN contrasts, either the mean or the standard deviation of the load stiffness sequence was held constant while the other parameter varied systematically. In WEBER contrast, mean and standard deviation scaled proportionally over the contrast. The zero location of the transfer function moved toward the origin as variability increased. This trend in the zero location was the result of an unbalance in the decrease in the influence of previous load and the decrease of effective limb compliance with increasing variability. Specifically, the decrease in the influence of prior load was greater than the decrease in effective limb compliance. Effective limb compliance decreased to a larger extent in the MEAN and WEBER contrasts, which both presented an increase in mean load. In the MEAN contrast, the decrease in effective limb compliance with increasing mean load was balanced by an equivalent decrease in the influence of prior load, resulting in no significant change in the transfer function zero location. No changes in the influence of prior errors were observed in any of the contrasts. Thus, motor adaptation adjusts in two ways: the influence of prior load on subsequent movements decreases both when the environment is more variable and when effective limb compliance decreases with the mean load.
Hydrodynamic Simulation of the Cosmological X-Ray Background

We use a hydrodynamic simulation of an inflationary cold dark matter model with a cosmological constant to predict properties of the extragalactic X-ray background (XRB). We focus on emission from the intergalactic medium (IGM), with particular attention to diffuse emission from warm-hot gas that lies in relatively smooth filamentary structures between galaxies and galaxy clusters. We also include X-rays from point sources associated with galaxies in the simulation, and we make maps of the angular distribution of the emission. Although much of the X-ray luminous gas has a filamentary structure, the filaments are not evident in the simulated maps because of projection effects. In the soft (0.5-2 keV) band, our calculated mean intensity of radiation from intergalactic and cluster gas is 2.3 × 10-12 ergs-1 cm-2 deg-2, 35% of the total softband emission. This intensity is compatible at the ~1 σ level with estimates of the unresolved soft background intensity from deep ROSAT and Chandra measurements. Only 4% of the hard (2-10 keV) emission is associated with intergalactic gas. Relative to active galactic nuclei flux, the IGM component of the XRB peaks at a lower redshift (median z ~ 0.45) and spans a narrower redshift range, so its clustering makes an important contribution to the angular correlation function of the total emission. The clustering on the scales accessible to our simulation (0.′1-10') is significant, with an amplitude roughly consistent with an extrapolation of recent ROSAT results to small scales. A cross-correlation analysis of the XRB against nearby galaxies taken from a simulated redshift survey also yields a strong signal from the IGM. Our conclusions about the soft background intensity differ from those of some recent papers that have argued that the expected emission from gas in galaxy, group, and cluster halos would exceed the observed background unless much of the gas is expelled by supernova feedback. We obtain reasonable compatibility with current observations in a simulation that incorporates cooling, star formation, and only modest feedback. A clear prediction of our model is that the unresolved portion of the soft XRB will remain mostly unresolved even as observations reach deeper point-source sensitivity.
Distribution and Determinants of Unmet Need for Supportive Care Among Women with Breast Cancer in China

Background The aim of this study was to determine the need for supportive care among women suffering from breast cancer in China and to identify its potential determinants to inform the development of effective and efficient healthcare services across different settings. Material/Methods In a tertiary-care hospital in Weifang, China, between July 2015 and January 2016, all women attending the Breast Cancer Clinic for regular physical examinations after treatment for breast cancer were consecutively recruited. The 34-item Supportive Care Needs Survey tool (Chinese version) (SCNS-SF34-C) was used to assess the unmet needs among participants. Results Among 264 recruited patients, based on at least single-item endorsement, 60.2% had moderate to high level of need for supportive care, while only 13.3% expressed no need. Lack of information regarding health systems was the most common domain with moderate to high unmet needs, more so among rural patients (8 vs. 5 out of 10). In each information-related domain, huge unmet need was observed among all patients irrespective of urban or rural residence. Both overall and individual information-related domain-specific unmet needs were significantly higher among rural patients as opposed to their urban counterparts. Multiple regression analyses revealed a significant rural-urban variation of unmet needs. Moreover, education and post-diagnosis time duration were negatively associated with unmet needs while stage of cancer was positively associated with these unmet needs. Conclusions There is a huge burden of unmet needs for information on the healthcare system among breast cancer survivors in China. Rural residence, less education, advanced stage of cancer, and shorter duration since diagnosis were the identified determinants requiring targeted intervention.
The severe complication of Stevens–Johnson syndrome induced by long-term clozapine treatment in a male schizophrenia patient: a case report

Introduction: Stevens–Johnson syndrome (SJS) is a severe adverse drug reaction that can result in disability and mortality. SJS is defined as having a widespread distribution throughout the whole body surface area with <10% extent of skin detachment and skin lesions. Some drugs, such as carbamazepine, have been reported to have a greater correlation to SJS. Although clozapine use has been mentioned as a risk factor for development of SJS, no report has clearly described the features of SJS as a reaction to clozapine use. Herein, we report the case of a patient presenting SJS after long-term clozapine treatment. Case report: Mr A was a 54-year-old male with a diagnosis of chronic schizophrenia. He was hospitalized in a mental institute and received clozapine 200 mg/day for 2 years, without discomfort or drug side effects. He developed acute-onset mouth edema, multiple oral and ocular ulcers, oral and ocular mucosa swelling, and multiple erythematous skin rashes over his entire body and extremities with hypertension and high fever. SJS was diagnosed after referral to a general hospital. Results The SJS subsided under supportive treatment. Conclusion Accumulated lymphocytes and macrophages in the epidermis and elevated TNF-α might cause an immune reaction and apoptosis and result in the clinical presentation of SJS. Clozapine is believed to modulate the immunologic reaction, and therefore might induce SJS through immunomodulation. This case highlights the importance of considering the possibility of SJS resulting from the use of drugs for which there are no reports of such a severe complication.
Contribution of Human Lung Parenchyma and Leukocyte Influx to Oxidative Stress and Immune System-Mediated Pathology following Nipah Virus Infection

ABSTRACT Nipah virus (NiV) is a zoonotic emerging paramyxovirus that can cause fatal respiratory illness or encephalitis in humans. Despite many efforts, the molecular mechanisms of NiV-induced acute lung injury (ALI) remain unclear. We previously showed that NiV replicates to high titers in human lung grafts in NOD-SCID/γ mice, resulting in a robust inflammatory response. Interestingly, these mice can undergo human immune system reconstitution by the bone marrow, liver, and thymus (BLT) reconstitution method, in addition to lung tissue engraftment, giving altogether a realistic model to study human respiratory viral infections. Here, we characterized NiV Bangladesh strain (NiV-B) infection of human lung grafts from human immune system-reconstituted mice in order to identify the overall effect of immune cells on NiV pathogenesis of the lung. We show that NiV-B replicated to high titers in human lung grafts and caused similar cytopathic effects irrespective of the presence of human leukocytes in mice. However, the human immune system interfered with virus spread across lung grafts, responded to infection by leukocyte migration to small airways and alveoli of the lung grafts, and accelerated oxidative stress in lung grafts. In addition, the presence of human leukocytes increased the expression of cytokines and chemokines that regulate inflammatory influx to sites of infection and tissue damage. These results advance our understanding of how the immune system limits NiV dissemination and contributes to ALI and inform efforts to identify therapeutic targets. IMPORTANCE Nipah virus (NiV) is an emerging paramyxovirus that can cause a lethal respiratory and neurological disease in humans. Only limited data are available on NiV pathogenesis in the human lung, and the relative contribution of the innate immune response and NiV to acute lung injury (ALI) is still unknown. Using human lung grafts in a human immune system-reconstituted mouse model, we showed that the NiV Bangladesh strain induced cytopathic lesions in lung grafts similar to those described in patients irrespective of the donor origin or the presence of leukocytes. However, the human immune system interfered with virus spread, responded to infection by leukocyte infiltration in the small airways and alveolar area, induced oxidative stress, and triggered the production of cytokines and chemokines that regulate inflammatory influx by leukocytes in response to infection. Understanding how leukocytes interact with NiV and cause ALI in human lung xenografts is crucial for identifying therapeutic targets.
Prevalence of Gestational Diabetes Mellitus in Korea: A National Health Insurance Database Study

Aims/Introduction This study aimed to estimate the prevalence of gestational diabetes mellitus (GDM) and use of anti-diabetic medications for patients with GDM in Korea, using data of the period 2007–2011 from the Health Insurance Review and Assessment (HIRA) database, which includes the claims data of 97% of the Korean population. Materials and Methods We used the Healthcare Common Procedure Coding System codes provided by the HIRA to identify women with delivery in the HIRA database between 2009 and 2011. GDM was defined according to ICD-10 codes, and patients with pre-existing diabetes between January 1, 2007 and pregnancy were excluded. A Poisson regression was performed to evaluate the trends in annual prevalence rates. Results The annual numbers of deliveries in 2009–2011 were 479,160 in 2009, 449,747 in 2010, and 377,374 in 2011. The prevalence of GDM during that period was 7.5% in 2009–2011: 5.7% in 2009, 7.8% in 2010, and 9.5% in 2011. The age-stratified analysis showed that the prevalence of GDM was highest in women aged 40–44 years, at 10.6% in 2009–2011, and that the annual prevalence significantly increased even in young women aged 20–29 years during that period (P < 0.05). More than 95% of the patients with GDM did not take any anti-diabetic medication. Among the anti-diabetic medications prescribed for patients with GDM, insulin was most commonly prescribed (for >98% of the patients with GDM on medication). Conclusions The prevalence of GDM in Korean women recently reached 5.7–9.5% in recent years. This represents a public health concern that warrants proper screening and medical care for GDM in women during the childbearing years.
Association Between Response to Etrolizumab and Expression of Integrin αE and Granzyme A in Colon Biopsies of Patients With Ulcerative Colitis.

BACKGROUND & AIMS Etrolizumab is a humanized monoclonal antibody against the β7 integrin subunit that has shown efficacy vs placebo in patients with moderate to severely active ulcerative colitis (UC). Patients with colon tissues that expressed high levels of the integrin αE gene (ITGAE) appeared to have the best response. We compared differences in colonic expression of ITGAE and other genes between patients who achieved clinical remission with etrolizumab vs those who did. METHODS We performed a retrospective analysis of data collected from 110 patients with UC who participated in a phase 2 placebo-controlled trial of etrolizumab, as well as from 21 patients with UC or without inflammatory bowel disease (controls) enrolled in an observational study at a separate site. Colon biopsies were collected from patients in both studies and analyzed by immunohistochemistry and gene expression profiling. Mononuclear cells were isolated and analyzed by flow cytometry. We identified biomarkers associated with response to etrolizumab. In the placebo-controlled trial, clinical remission was defined as total Mayo Clinic Score ≤2, with no individual subscore >1, and mucosal healing was defined as endoscopic score ≤1. RESULTS Colon tissues collected at baseline from patients who had a clinical response to etrolizumab expressed higher levels of T-cell-associated genes than patients who did not respond (P < .05). Colonic CD4(+) integrin αE(+) cells from patients with UC expressed higher levels of granzyme A messenger RNA (GZMA mRNA) than CD4(+) αE(-) cells (P < .0001); granzyme A and integrin αE protein were detected in the same cells. Of patients receiving 100 mg etrolizumab, a higher proportion of those with high levels of GZMA mRNA (41%) or ITGAE mRNA (38%) than those with low levels of GZMA (6%) or ITGAE mRNA (13%) achieved clinical remission (P < .05) and mucosal healing (41% GZMA(high) vs 19% GZMA(low) and 44% ITGAE(high) vs 19% ITGAE(low)). Compared with ITGAE(low) and GZMA(low) patients, patients with ITGAE(high) and GZMA(high) had higher baseline numbers of epithelial crypt-associated integrin αE(+) cells (P < .01 for both), but a smaller number of crypt-associated integrin αE(+) cells after etrolizumab treatment (P < .05 for both). After 10 weeks of etrolizumab treatment, expression of genes associated with T-cell activation and genes encoding inflammatory cytokines decreased by 40%-80% from baseline (P < .05) in patients with colon tissues expressing high levels of GZMA at baseline. CONCLUSIONS Levels of GZMA and ITGAE mRNAs in colon tissues can identify patients with UC who are most likely to benefit from etrolizumab; expression levels decrease with etrolizumab administration in biomarker(high) patients. Larger, prospective studies of markers are needed to assess their clinical value.
Sport Concussion Management Using Facebook: A Feasibility Study of an Innovative Adjunct "iCon".

CONTEXT Sport concussion is currently the focus of much international attention. Innovative methods to assist athletic trainers in facilitating management after this injury need to be investigated. OBJECTIVE To investigate the feasibility of using a Facebook concussion-management program termed iCon (interactive concussion management) to facilitate the safe return to play (RTP) of young persons after sport concussion. DESIGN Observational study. SETTING Facebook group containing interactive elements, with moderation and support from trained health care professionals. PATIENTS OR OTHER PARTICIPANTS Eleven participants (n = 9 men, n = 2 women; range, 18 to 28 years old) completed the study. DATA COLLECTION AND ANALYSIS The study was conducted over a 3-month period, with participant questionnaires administered preintervention and postintervention. The primary focus was on the qualitative experiences of the participants and the effect of iCon on their RTP. Usage data were also collected. RESULTS At the completion of the study, all participants (100%) stated that they would recommend an intervention such as iCon to others. Their supporting quotes all indicated that iCon has the potential to improve the management of concussion among this cohort. Most participants (n = 9, 82%) stated they were better informed with regard to their RTP due to participating in iCon. CONCLUSIONS This interactive adjunct to traditional concussion management was appreciated among this participant group, which indicates the feasibility of a future, larger study of iCon. Athletic trainers should consider the role that multimedia technologies may play in assisting with the management of sport concussion.
Functional Promoter -308G>A Variant in Tumor Necrosis Factor α Gene Is Associated with Risk and Progression of Gastric Cancer in a Chinese Population

Background Tumor necrosis factor-α (TNF-α) plays a crucial role in the development and progression of gastric cancer. A functional polymorphism, -308 G>A (rs1800629), which is located in the promoter of TNFA gene, has been suggested to alter the production of TNF-α and influence cancer risk. In the present study, we sought to investigate whether this polymorphism has effects on the risk and progression of gastric cancer in a Chinese population. Methods We genotyped the TNFA -308 G>A polymorphism using the TaqMan method in a two-stage case-control study comprising a total of 1686 gastric cancer patients and 1895 cancer-free subjects. The logistic regression was used to assess the genetic associations with occurrence and progression of gastric cancer. Results We found a significant association between the variant genotypes and increased risk of gastric cancer [P = 0.034, odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.01–1.67, GA/AA vs. GG]. Similar results were observed in the follow-up replication study. When combined the data from the two studies, we found a more significant association (P = 0.001, OR = 1.34, 95%CI = 1.13–1.59), especially for older subjects (>65 years). Furthermore, the patients carrying the variant genotypes had a significantly greater prevalence of T4 stage of disease (P = 0.001, OR = 2.19, 95%CI = 1.39–3.47) and distant metastasis (P = 0.013, OR = 1.61, 95%CI = 1.10–2.35). Conclusions Our results suggest that the functional promoter -308 G>A polymorphism in TNFA influence the susceptibility and progression of gastric cancer in the Chinese population.
Prognostic Value of White Blood Cell Counts and C-reactive Protein in Acute Ischemic Stroke Patients After Intravenous Thrombolysis.

BACKGROUND The prognostic value of White Blood Cell (WBC) counts and C-reactive Protein (CRP) in clinical outcomes of Acute Ischemic Stroke (AIS) patients after Intravenous Thrombolysis (IVT) remains unknown. We investigated the association of WBC counts and CRP with 3-month functional outcomes and all-cause mortality in AIS patients. METHODS 447 AIS patients treated with IVT between May 2010 and May 2017 were enrolled. WBC counts and CRP were measured within 24 hours after IVT. The main outcomes included poor functional outcomes (modified Rankin score ≥3) at 3 months and 3-month all-cause mortality. RESULTS High WBC counts were associated with poor functional outcomes (adjusted OR (odds ratio) 4.48; 95% CI (confidence interval) 2.00-10.03; P-trend<0.001) and with all-cause mortality (adjusted HR (hazard ratio) 2.19; 95% CI 1.07-4.49; P-trend=0.018). In addition, high CRP levels were associated with poor functional outcomes (adjusted OR 4.95; 95% CI 1.39-17.65; Ptrend= 0.002). However, no significant association between high CRP levels and all-cause mortality was observed (adjusted HR 2.61; 95% CI 0.80-8.47; P-trend=0.138). CONCLUSION Our analysis indicated that elevated WBC counts and CRP levels after IVT can independently predict poor outcome among AIS patients.