Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovery and Characterization of the 1918 Pandemic Influenza Virus in Historical Context

The 2005 completion of the entire genome sequence of the 1918 H1N1 pandemic influenza virus represents both a beginning and an end. Investigators have already begun to study the virus in vitro and in vivo to better understand its properties, pathogenicity, transmissibility and elicitation of host responses. Although this is an exciting new beginning, characterization of the 1918 virus also represents the culmination of over a century of scientific research aiming to understand the causes of pandemic influenza. In this brief review we attempt to place in historical context the identification and sequencing of the 1918 virus, including the alleged discovery of a bacterial cause of influenza during the 1889–1893 pandemic, the controversial detection of ‘filter-passing agents’ during the 1918–1919 pandemic, and subsequent breakthroughs in the 1930s that led to isolation of human and swine influenza viruses, greatly influencing the development of modern virology.
Modulation of movement‐associated cortical activation by transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) is currently attracting increasing interest as a tool for neurorehabilitation. However, local and distant effects of tDCS on motor‐related cortical activation patterns remain poorly defined, limiting the rationale for its use. Here we describe the results of a functional magnetic resonance imaging (MRI) experiment designed to characterize local and distant effects on cortical motor activity following excitatory anodal stimulation and inhibitory cathodal stimulation. Fifteen right‐handed subjects performed a visually cued serial reaction time task with their right hand in a 3‐T MRI scanner both before and after 10 min of 1‐mA tDCS applied to the left primary motor cortex (M1). Relative to sham stimulation, anodal tDCS led to short‐lived activation increases in the M1 and the supplementary motor area (SMA) within the stimulated hemisphere. The increase in activation in the SMA with anodal stimulation was found also when directly comparing anodal with cathodal stimulation. Relative to sham stimulation, cathodal tDCS led to an increase in activation in the contralateral M1 and dorsal premotor cortex (PMd), as well as an increase in functional connectivity between these areas and the stimulated left M1. These increases were also found when directly comparing cathodal with anodal stimulation. Significant within‐session linear decreases in activation occurred in all scan sessions. The after‐effects of anodal tDCS arose primarily from a change in the slope of these decreases. In addition, following sham stimulation compared with baseline, a between‐session decrease in task‐related activity was found. The effects of cathodal tDCS arose primarily from a reduction of this normal decrease.
Creation of new bone by the percutaneous injection of human bone marrow stromal cell and HA/TCP suspensions.

BACKGROUND The in vivo transplantation assay has become a valuable tool for assessing the osteogenic potential of diverse cell populations. It has required that cells are cotransplanted with a matrix into recipient animals using large incisions and extensive dissections. Here, we demonstrate that transplants of an osteogenic cell population, bone marrow stromal cells (BMSCs), are capable of assembling into mature bone organs when injected as suspensions of cells and a particulate matrix. METHODS Human BMSCs, along with hydroxyapatite/tricalcium phosphate (HA/TCP) particles, were placed either into the dorsal subcutaneous space or onto the calvarium of immunodeficient mice, either via injection or via a wide operative exposure. Transplants were harvested from 7 to 110 weeks later; their histologic and mechanical properties and their cellular origin were analyzed. RESULTS A total of 43 transplants were evaluated. The extent of new bone and hematopoiesis, the bone's adherence to the underlying mouse calvarium, and the bone elastic modulus and hardness were comparable between the two groups. In situ hybridization confirmed a human origin of the new bone. CONCLUSIONS Our data indicate that BMSCs and HA/TCP particles, when injected as a suspension, can assemble into mature bone organs, and that this bone has histologic and mechanical properties similar to bone formed in standard transplants delivered through a large incision. These results open the possibility for assessing the osteogenic capacities of cell populations, for modeling bone formation and repair and for treating bone deficits, all in the context of minimal surgical intervention or soft tissue disruption.
Is It Time to Change the Type 2 Diabetes Treatment Paradigm? Yes! GLP-1 RAs Should Replace Metformin in the Type 2 Diabetes Algorithm

Most treatment guidelines, including those from the American Diabetes Association/European Association for the Study of Diabetes and the International Diabetes Federation, suggest metformin be used as the first-line therapy after diet and exercise. This recommendation is based on the considerable body of evidence that has accumulated over the last 30 years, but it is also supported on clinical grounds based on metformin’s affordability and tolerability. As such, metformin is the most commonly used oral antihyperglycemic agent in the U.S. However, based on the release of newer agents over the recent past, some have suggested that the modern approach to disease management should be based upon identification of its etiology and correcting the underlying biological disturbances. That is, we should use interventions that normalize or at least ameliorate the recognized derangements in physiology that drive the clinical manifestation of disease, in this circumstance, hyperglycemia. Thus, it is argued that therapeutic interventions that target glycemia but do not correct the underlying pathogenic disturbances are unlikely to result in a sustained benefit on the disease process. In our field, there is an evolving debate regarding the suggested first step in diabetes management and a call for a new paradigm. Given the current controversy, we provide a Point-Counterpoint debate on this issue. In the point narrative below that precedes the counterpoint narrative, Drs. Abdul-Ghani and DeFronzo provide their argument that a treatment approach for type 2 diabetes based upon correcting the underlying pathophysiological abnormalities responsible for the development of hyperglycemia provides the best therapeutic strategy. Such an approach requires a change in the recommendation for first-line therapy from metformin to a GLP-1 receptor agonist. In the counterpoint narrative that follows Drs. Abdul-Ghani and DeFronzo’s contribution, Dr. Inzucchi argues that, based on the medical community’s extensive experience and the drug’s demonstrated efficacy, safety, low cost, and cardiovascular benefits, metformin should remain the “foundation therapy” for all patients with type 2 diabetes, barring contraindications. —William T. Cefalu Chief Scientific, Medical & Mission Officer, American Diabetes Association
Cancer Mortality among Women Frequently Exposed to Radiographic Examinations for Spinal Disorders

Abstract We studied cancer mortality in a cohort of 5,573 women with scoliosis and other spine disorders who were diagnosed between 1912 and 1965 and were exposed to frequent diagnostic X-ray procedures. Patients were identified from medical records in 14 orthopedic medical centers in the United States and followed for vital status and address through December 31, 2004, using publicly available regional, state and nationwide databases. Causes of death were obtained from death certificates or through linkage with the National Death Index (NDI). Statistical analyses included standardized mortality ratios (SMR = observed/expected) based on death rates for U.S. females and internal comparisons using Cox regression models with attained age as the time scale. Diagnostic radiation exposure was estimated from radiology files for over 137,000 procedures; estimated average cumulative radiation doses to the breast, lung, thyroid and bone marrow were 10.9, 4.1, 7.4 and 1.0 cGy, respectively. After a median follow-up period of 47 years, 1527 women died, including 355 from cancer. Cancer mortality was 8% higher than expected (95% CI = 0.97–1.20). Mortality from breast cancer was significantly elevated (SMR = 1.68; 95% CI: 1.38–2.02), whereas death rates from several other cancers were below expectation, in particular lung (SMR = 0.77), cervical (SMR = 0.31), and liver (SMR = 0.17). The excess relative risk (ERR) for breast cancer mortality increased significantly with 10-year lagged radiation dose to the breast (ERR/Gy = 3.9; 95% CI: 1.0–9.3).
The risks and benefits of long‐term use of hydroxyurea in sickle cell anemia: A 17.5 year follow‐up

A randomized, controlled clinical trial established the efficacy and safety of short‐term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long‐term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow‐up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at α = 0.05 level (P‐value <0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person‐years), mortality was reduced in individuals with long‐term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long‐term exposure. Twenty‐four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for <5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long‐term use of hydroxyurea is safe and might decrease mortality. Am. J. Hematol. 2010. © 2010 Wiley‐Liss, Inc.
Epidemiology of nonkeratinocytic skin cancers among persons with AIDS in the United States

Objective:Immunosuppression may increase risk for some skin cancers. We evaluated skin cancer epidemiology among persons with AIDS. Design:We linked data from population-based US AIDS and cancer registries to evaluate risk of nonkeratinocytic skin cancers (melanoma, Merkel cell carcinoma, and appendageal carcinomas, including sebaceous carcinoma) in 497 142 persons with AIDS. Methods:Standardized incidence ratios (SIRs) were calculated to relate skin cancer risk to that in the general population. We used logistic regression to compare risk according to demographic factors, CD4 cell count, and a geographic index of ultraviolet radiation exposure. Results:From 60 months before to 60 months after AIDS onset, persons with AIDS had elevated risks of melanoma (SIR = 1.3, 95% confidence interval 1.1–1.4, n = 292 cases) and, more strongly, of Merkel cell carcinoma (SIR = 11, 95% confidence interval 6.3–17, n = 17) and sebaceous carcinoma (SIR = 8.1, 95% confidence interval 3.2–17, n = 7). Risk for appendageal carcinomas increased with progressive time relative to AIDS onset (P trend = 0.03). Risk of these skin cancers was higher in non-Hispanic whites than other racial/ethnic groups, and melanoma risk was highest among men who have sex with men. Melanoma risk was unrelated to CD4 cell count at AIDS onset (P = 0.32). Risks for melanoma and appendageal carcinomas rose with increasing ultraviolet radiation exposure (P trend <10−4 and P trend = 10−3, respectively). Conclusion:Among persons with AIDS, there is a modest excess risk of melanoma, which is not strongly related to immunosuppression and may relate to ultraviolet radiation exposure. In contrast, the greatly increased risks for Merkel cell and sebaceous carcinoma suggest an etiologic role for immunosuppression.
Gag-Specific CD8+ T Lymphocytes Recognize Infected Cells before AIDS-Virus Integration and Viral Protein Expression1

CD8+ T cells are a key focus of vaccine development efforts for HIV. However, there is no clear consensus as to which of the nine HIV proteins should be used for vaccination. The early proteins Tat, Rev, and Nef may be better CD8+ T cell targets than the late-expressed structural proteins Gag, Pol, and Env. In this study, we show that Gag-specific CD8+ T cells recognize infected CD4+ T lymphocytes as early as 2 h postinfection, before proviral DNA integration, viral protein synthesis, and Nef-mediated MHC class I down-regulation. Additionally, the number of Gag epitopes recognized by CD8+ T cells was significantly associated with lower viremia (p = 0.0017) in SIV-infected rhesus macaques. These results suggest that HIV vaccines should focus CD8+ T cell responses on Gag.
EXTRACORPOREAL PERFUSION FOR OBTAINING POSTMORTEM HOMOGRAFTS.

Functional renal homografts have been obtained as long as 14 hours post mortem by a technique of extracorporeal cadaver perfusion. The method has also given satisfactory liver homografts after perfusion up to 2 hours. Details of the technique and experimental and clinical applications are described. Analysis of the data indicates that optimal perfusion times for renal homografts should not exceed 6 hours. For the liver, 2 hours appears to be the maximum tolerable period of perfusion. For clinical application, certain adjuvant measures are important. Perfusion failure has been encountered in human cadavers, presumably as a result of the presence of a reduced blood volume. This can be prevented by acute postmortem expansion of the intravascular volume with compatible whole blood or plasma. Proper donor selection is as important a factor as the method used for preservation. Indirect evidence is cited that premortem tissue injury in protracted terminal disease may be a greater deterent to success than the parenchymal damage which occurs during postmortem perfusion. The extension of this technique for the procurement of other organs such as heart and lung is discussed.
Defining the Relationships Among Retinal Function, Layer Thickness and Visual Behavior During Oxidative Stress-Induced Retinal Degeneration

Abstract Purpose: The purpose of this study was to identify how changes in retinal structure and function correlate with visual deficits during increasing amounts of retinal degeneration. Materials and methods: Retinal degeneration was induced in adult mice by subretinal injections of paraquat (PQ) (0.2–1 mM). Retinal anatomy and photoreceptor layer thickness were quantified by histology and optical coherence tomography (OCT), retinal function was measured using electroretinography (ERG), and visual behavior were measured by optokinetic tracking, at 1 to 3 week post-injury. Results: Photoreceptor layer structure, function and visual behavior declined at a linear rate over time following PQ-induced degeneration, with the correlations between outcome measures being lowest at mild injury levels and increasing with injury severity. Overall reductions in visual acuity were highly correlated with declines in retinal thickness (r 2 = 0.78) and function (r 2 = 0.67) and retinal thickness correlated with photoreceptor function (r 2 = 0.72). ERG a-wave scotopic amplitudes showed a stronger correspondence to retinal structure and visual behavior than b-waves. Conclusions: Measurements of photoreceptor loss at the structural and functional levels showed good correspondence with degeneration-associated changes in visual behavior after oxidative stress injury. The results provide new insight about the relative kinetics of measurements of retinal degeneration induced by oxidative stress, which could guide the choice of optimal outcome measurements for other retinal diseases.
Speech Recognition Outcomes After Cochlear Reimplantation Surgery

This study compares speech recognition outcomes before and after cochlear reimplantation surgery, in relation to clinical factors known before and at time of surgery. Between 2006 and 2015, 2,055 adult cochlear implant surgeries were conducted at this center, of which 87 were reimplantation surgeries (4.2%). Speech recognition scores (SRS) assessed before and after reimplantation were available for 54 adults. Overall, SRS measured after reimplantation were similar to the best SRS obtained by the patient and greater than the last SRS measured before surgery. Additional complications were noted in the clinical files of all patients for which reimplantation was considered unsuccessful (16%).
Enzymatic and Pro-Inflammatory Activities of Bothrops lanceolatus Venom: Relevance for Envenomation

Bothrops lanceolatus, commonly named ‘Fer-de-Lance’, is an endemic snake of the French Caribbean Island of Martinique. Envenomations by B. lanceolatus present clinical aspects characterized by systemic thrombotic syndrome and important local inflammation, involving edema and pain but limited hemorrhage. To investigate mechanisms of venom-induced inflammation, B. lanceolatus venom was characterized, its cross-reactivity with bothropic antivenom explored, its cytotoxicity on human keratinocytes and vascular cells, and the production of cytokines and chemokines were analyzed. We used electrophoretic separation, zymography, colorimetric or fluorimetric enzymatic assays, and immunochemical assays. Therapeutic South American bothropic antivenom cross-reacted with B. lanceolatus venom and completely or partially abolished its PLA2, hyaluronidase, and proteolytic activities, as well as its cytotoxicity for keratinocytes. The substrate specificity of B. lanceolatus venom proteases was emphasized. B. lanceolatus venom cytotoxicity was compared to the B. jararaca venom. Both venoms were highly cytotoxic for keratinocytes (HaCaT), whereas B. lanceolatus venom showed particularly low toxicity for endothelial cells (EAhy926). Patterns of cytokine and chemokine production by cells exposed to the venoms were highly pro-inflammatory. Thus, the results presented here show that B. lanceolatus venom toxins share important antigenic similarities with South American Bothrops species toxins, although their proteases have acquired particular substrate specificity. Moreover, the venom displays important cytotoxic and pro-inflammatory action on human cell types such as keratinocytes and endothelial cells, which are important players in the local and systemic compartments affected by the envenomation.
ICAM‐1 co‐stimulation has differential effects on the activation of CD4+ and CD8+ T cells

T cells play a central role in the initiation, maintenance and regulation of the immune response. Effector responses of T cells are controlled by complex combinations of lymphokines and adhesion/co‐stimulatory molecule signals. To isolate the effects of the adhesion/co‐stimulatory molecule ICAM‐1, we have stimulated purified murine CD4+ and CD8+ T cells with plate‐bound anti‐CD3 in the presence or absence of plate‐bound soluble ICAM‐1. In this report, we demonstrate that the co‐immobilization of soluble ICAM‐1 and anti‐CD3 leads to a much greater increase in IL‐2 production by CD8+ T cells than CD4+ T cells. The ICAM‐1‐induced enhancement we observed has differential sensitivity to LFA‐1 blockade, depending on the T cell subsets and cytokine evaluated. These effects may play an important role in the generation and modulation of immune responses.
Minimally Cultured Tumor-infiltrating Lymphocytes Display Optimal Characteristics for Adoptive Cell Therapy

Adoptive cell therapy (ACT) with tumor-reactive lymphocytes in patients with refractory melanoma can result in tumor regression and prolonged survival. Generating tumor-reactive lymphocyte cultures is technically difficult and resource intensive; these limitations have restricted the widespread application of ACT. Tumor-infiltrating lymphocytes (TIL) from melanoma contain tumor antigen-reactive cells. The “standard” method for producing TIL cultures for clinical administration requires extended in vitro expansion in interleukin-2, then identification of tumor-reactive cells by immunologic assays. We show here that limitations in reagents and methods during screening underrepresent the actual reactivity of TIL cultures. Furthermore, the extended culture times necessitated by the screening assays resulted in telomere shortening and reduced expression of CD27 and CD28 in the TIL cultures, properties that our prior studies showed are correlated with in vivo persistence and clinical response. We have thus developed an alternative “young” TIL method that demonstrated superior in vitro attributes compared with standard TIL. This approach uses the entire resected tumor to rapidly expand TIL for administration without in vitro testing for tumor recognition. Our observations suggest that younger TIL can have an undetermined but high level of antigen reactivity, and other advantageous attributes such as long telomeres and high levels of CD27 and CD28. We suggest that minimally cultured, unselected lymphocytes represent an alternative strategy for generating TIL cultures suitable for use in ACT that, if effective in vivo, may facilitate the widespread application of this approach to a broader population of patients with melanoma.
The Prediction of User Topic Interest Based on Tags and Interaction of Users

With the rapid development of the Internet, more and more people use social networks to share information and express their views, which lead to a vigorous growth of information. How to select useful and interesting information for users, that is user topic interest, gets more and more attention. Tag functionality in microblog can get user topic interests easily and achieve information recommendation effectively. To deal with the situation that there are few or no tags for most users in microblog, a user topic interest prediction method based on the tag content and interactive relations of users is proposed. The method utilizes Wikipedia to extend the tags and produce a preliminary estimate of the tags' importance. What's more, interactive relations and propagation analysis of different tags are studied. An extensive empirical study using real Sina Microblog data clearly demonstrates that our method has a better performance in user topic interest prediction.