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Systemic Lupus Erythematosus (SLE) is an autoimmune disease resulting in autoantibody production, immune complex deposition, and complement activation. The standard biomarkers such as anti-dsDNA and complements (C3 and C4) do not always correlate with active clinical SLE. The heterogeneity of SLE patients may require additional biomarkers to designate disease activity. Ninety SLE patients participated in this study. Evaluation of disease activity was achieved with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and modified SLEDAI-2K. The measured serum biomarkers were anti-dsDNA, C3, C4, ESR, interleukin-6 (IL-6), and circulating immune complexes (CIC). IL-6, ESR and CIC significantly increased in active clinical SLE. Complement, anti-dsDNA, ESR and CIC correlated with SLEDAI-2K while only anti-dsDNA, CIC, ESR and IL-6 correlated with modified SLEDAI-2K. A combination of biomarkers gave a higher odds ratio (OR) than any single biomarker. A combination of IL-6 or CIC exhibited the highest OR (OR = 7.27, 95%CI (1.99–26.63), p = 0.003) while either complement or anti-dsDNA showed a moderate odds ratio (OR = 3.14, 95%CI (1.16–8.48), p = 0.024) of predicting clinical active SLE. The combination of CIC and IL-6 strongly predicts active clinical SLE. CIC and IL-6 can be used in addition to standard biomarkers to determine SLE activity.

Snakebite, classified by World Health Organization as a neglected tropical disease, causes more than 100,000 deaths and 2 million injuries per year. Currently, available antivenoms do not bind with strong specificity to target toxins, which means that severe complications can still occur despite treatment. Moreover, the cost of antivenom is expensive. Knowledge of venom compositions is fundamental for producing a specific antivenom that has high effectiveness, low side effects, and ease of manufacture. With advances in mass spectrometry techniques, venom proteomes can now be analyzed in great depth at high efficiency. However, these techniques require genomic and transcriptomic data for interpreting mass spectrometry data. This study aims to establish and incorporate genomics, transcriptomics, and proteomics data to study venomics of a venomous snake, Daboia siamensis . Multiple proteins that have not been reported as venom components of this snake such as hyaluronidase-1, phospholipase B, and waprin were discovered. Thus, multi-omics data are advantageous for venomics studies. These findings will be valuable not only for antivenom production but also for the development of novel therapeutics.

Since its inception over 20 years ago, gene enrichment has been largely associated with curated gene lists (e.g. GO) that are constructed to represent various biological concepts; the cell cycle, cancer drivers, protein-protein interactions, etc. Researchers expect that a comparison of their own lab-generated lists with curated lists should produce insight. Despite the abundance of such curated lists, we here show that they rarely outperform comparisons against existing individual lab-generated datasets when measured using standard statistical tests of study/study overlap. This demonstration is enabled by the WhatIsMyGene database, which we believe to be the single largest compendium of transcriptomic and micro-RNA perturbation data. The database also houses voluminous proteomic, cell type clustering, lncRNA, epitranscriptomic (etc.) data. In the case of enrichment tools that do incorporate specific lab studies in underlying databases, WIMG generally outperforms in the simple task of reflecting back to the user known aspects of the input set (cell type, the type of perturbation, species, etc.), enhancing confidence that unknown aspects of the input may also be revealed in the output. A limited number of GO lists are included in the database. However, these lists are assigned backgrounds, meaning that GO lists that are replete with abundant entities do not inordinately percolate to the highest ranking positions in output. We delineate a number of other features that should make WIMG indispensable in answering essential questions such as \"What processes are embodied in my gene list?\" and \"What does my gene do?\"Competing Interest StatementThe authors have declared no competing interest.Footnotes* I submitted a revision a couple hours ago. However, I noticed a glaring error (2 panels in Figure 4 are exactly the same) that needs to be corrected. My apologies!

Cynics point out that a cure for cancer has been \"around the corner\" for the last 50 years. Nevertheless, the recent convergence of deep DNA, RNA, and proteomic technologies with enhanced understanding of the nuances of the adaptive immune system has generated great optimism amongst researchers. The extraordinary heterogeneity of various cancers, once thought to be a major therapeutic hurdle, may now be bypassed via \"personalized\" vaccine treatments. Specifically, these treatments involve the identification of MHC-bound peptides that are unique to a patient's cancer (neoantigens), followed by immunization with peptides, RNA, or DNA that encodes these neoantigens via various delivery systems, thus amplifying the immune system's response to the particular cancer. Such approaches have shown dramatic results in animal studies. Not surprisingly, then, the field of neoantigen-based immunotherapy has advanced at a spectacular rate, necessitating that interested individuals stay apprised of recent developments. Following an introduction to the subject, we thus focus on aspects that are particularly fast-moving; the cellular sources of neoantigens, which are surprisingly diverse, the tools that are used for their identification, and the status of the numerous clinical trials that are now being conducted.

Sport advocates have suggested that athletic participation cultivates moral development, sportsmanship, self-reliance, and courage, to name but a few \"desirable\" character traits commonly associated with the sport experience. Yet, the empirical evidence to support these claims is fragmented and less than convincing. A need existed, therefore, to examine the assumption that sport builds character, and this needed to be addressed from both a conceptual and an empirical perspective. The primary purpose of this study was to resolve the definitional and theoretical limitations of previous research in this area. To accomplish this objective an investigation was conducted in three interrelated phases. In Phase 1 an exhaustive conceptual analysis of character was conducted within the social psychological literature. Relevant writings from the fields of philosophy, sociology, cultural anthropology, and psychoanalysis were also reviewed. Phase 2 utilized the Partial-Structure Paradigm of Social Cognition (Turiel, 1978, 1983) and focused on establishing conceptual linkages among each of the elements of character identified in Phase 1 (i.e., morality, ego-identity, psychosocial maturity, autonomy-assertiveness). Theoretical and operational definitions of character were formulated and a Conceptual Framework of Character Development was constructed. With the conceptual framework of character development in hand, Phase 3 focused on applying the framework to a conceptual analysis of character development in sport--that is, \"Does Sport Build Character?\" The major themes that emerged from this analysis were that sport exhibits limited potential for mature character development as it is presently practiced, and that the major factors influencing the direction of the effect of participation in sport are the social environment created by adult leaders and the structural limitations of organized sport itself. The \"type\" of character developed through the sport experience does not appear to represent the \"autonomous, moral, prosocial\" character that sport advocates would have us believe. Instead, it is concluded that sport, as it presently practiced, contributes to the development of a \"bureaucratic/marketing\" character orientation (Fromm, 1949; Sage, 1978). Clearly, there are a number of benefits derived from this character orientation, yet it does appear to also set limits on the athlete's ability to function effectively as an autonomous, moral, and self-reliant individual. The implications of this character orientation are discussed and future research directions are forwarded.

This work was concerned with the analysis of radiocarbon and radium in marine sediments, and the research was undertaken with a view to determining the age and rates of accumulation of such sediments by the radium dating technique.Several short cores of unconsolidated sediment were obtained from different areas of the North-East Atlantic Ocean, from depths ranging from 150-5000 m. These were all predominantly biological in origin, and were practically homogeneous throughout their length. The cores were dissected into thin (one centimetre) horizontal slices, dried, and subjected to analysis for 14 6C and 226 88Ra, using the assumption that the samples represented an undisturbed product of sedimentation, and the chronological sequence was therefore intact.The analysis for 14C was done using liquid scintillation counting, and the calcium carbonate fragment of the sediment was transformed into benzene for use as the counting fluid; this was combined with a suitable scintillation medium for counting. The conversion of calcium carbonate to benzene was achieved via the intermediates carbon dioxide, lithium carbide and acetylene, and a vacuum apparatus was built and developed to carry out these reactions.The analysis of 226Ra was also carried out by liquid scintillation counting using an aqueous/organic emulsion, following co-precipitation of radium with barium as the chlorides.

In his letter of Jan. 13 (Free For All], Lawrence J. Heim stated that J. Edgar Hoover disliked Martin Luther King not because he was black but because of those with whom he associated. However, if Heim had done his research, he would have found that Hoover designed a master plan to destroy...

Vaccination is one of public health's greatest achievements, responsible for saving billions of lives. Yet, 20% of children worldwide are not fully protected, leading to 1·5 million child deaths annually from vaccine-preventable diseases. Millions more people have severe disabling illnesses, cancers, and disabilities stemming from underimmunisation. Reasons for falling vaccination rates globally include low public trust in vaccines, constraints on affordability or access, and insufficient governmental vaccine investments. Consequently, an emerging crisis in vaccine hesitancy ranges from hyperlocal to national and worldwide. Outbreaks often originate in small, insular communities with low immunisation rates. Local outbreaks can spread rapidly, however, transcending borders. Following an assessment of underlying determinants of low vaccination rates, we offer an action based on scientific evidence, ethics, and human rights that spans multiple governments, organisations, disciplines, and sectors.

Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd , the fly homolog of OXR1 , which influenced lifespan and mtd expression in response to DR. Knockdown in adulthood inhibited DR-mediated lifespan extension in female flies. We found that mtd / OXR1 expression declines with age and it interacts with the retromer, which regulates trafficking of proteins and lipids. Loss of mtd / OXR1 destabilized the retromer, causing improper protein trafficking and endolysosomal defects. Overexpression of retromer genes or pharmacological restabilization with R55 rescued lifespan and neurodegeneration in mtd -deficient flies and endolysosomal defects in fibroblasts from patients with lethal loss-of-function of OXR1 variants. Multi-omic analyses in flies and humans showed that decreased Mtd/OXR1 is associated with aging and neurological diseases. mtd/OXR1 overexpression rescued age-related visual decline and tauopathy in a fly model. Hence, OXR1 plays a conserved role in preserving retromer function and is critical for neuronal health and longevity. Dietary restriction promotes healthy brain aging, but the mechanism is unknown. Here, the authors show that OXR1 is upregulated by dietary restriction and confers age-related neuroprotection by maintaining retromer-mediated protein and lipid trafficking.