Endlessly Browsable Topic Recommendations

Some users of search engines may not want to (or may be unable to) type in or speak out a search query. As another example, users may have limited or no knowledge of popular search platforms or engines. There is currently no mechanism for a search engine to recommend related topics to a user to enable a semi-autonomous browsing experience that can be endless. This disclosure describes techniques that utilize a topic graph to enable users to browse topics or explore interesting and contextual information without requiring the entry of a search query

Knockdown of menin affects pre-mRNA processing and promoter fidelity at the interferon-gamma inducible IRF1 gene

<p>Abstract</p> <p>Background</p> <p>The tumor suppressor menin (<it>MEN1</it>) is mutated in the inherited disease multiple endocrine neoplasia type I, and has several documented cellular roles, including the activation and repression of transcription effected by several transcription factors. As an activator, MEN1 is a component of the Set1-like mixed lineage leukemia (MLL) MLL1/MLL2 methyltransferase complex that methylates histone H3 lysine 4 (H3K4). MEN1 is localized to the signal transducer and activator of transcription 1 (STAT1)-dependent gene, interferon regulatory factor 1 (<it>IRF1)</it>, and is further recruited when <it>IRF1 </it>transcription is triggered by interferon-γ signaling.</p> <p>Results</p> <p>RNAi-mediated knockdown of MEN1 alters the H3K4 dimethylation and H3 acetylation profiles, and the localization of histone deacetylase 3, at <it>IRF1</it>. While MEN1 knockdown does not impact the rate of transcription, <it>IRF1 </it>heteronuclear transcripts become enriched in MEN1-depleted cells. The processed mRNA and translated protein product are concomitantly reduced, and the antiviral state is attenuated. Additionally, the transcription start site at the <it>IRF1 </it>promoter is disrupted in the MEN1-depleted cells. The H3K4 demethylase, lysine specific demethylase 1, is also associated with <it>IRF1</it>, and its inhibition alters H3K4 methylation and disrupts the transcription start site as well.</p> <p>Conclusions</p> <p>Taken together, the data indicate that MEN1 contributes to STAT1-activated gene expression in a novel manner that includes defining the transcription start site and RNA processing.</p

Autoimmune Lymphoproliferative Syndrome: an Update and Review of the Literature

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by immune dysregulation due to a defect in lymphocyte apoptosis. The clinical manifestations may be noted in multiple family members and include lymphadenopathy, splenomegaly, increased risk of lymphoma and autoimmune disease, which typically involve hematopoietic cell lines manifesting as multilineage cytopenias. Since the disease was first characterized in the early 1990s, there have been many advances in the diagnosis and management of this syndrome. The inherited genetic defect of many ALPS patients has involved (FAS) pathway signaling proteins, but there remain those patients who carry undefined genetic defects. Despite ALPS having historically been considered a primary immune defect presenting in early childhood, adult onset presentation is increasingly becoming recognized, and more so in genetically undefined patients and those with somatic FAS mutations. Thus, future research may identify novel pathways and/or regulatory proteins important in lymphocyte activation and apoptosis

Firearm Injury Prevention

Gun ownership is common and firearms are involved in the injury and death of a large number of children each year from both intentional and unintentional causes nationally. Physician counseling on firearm safety is an effective injury prevention method. This series of video modules was built to teach pediatric resident physicians about firearm injury prevention and safety counseling. The skills and tools provided can be used by physicians across a variety of disciplines.http://deepblue.lib.umich.edu/bitstream/2027.42/120512/1/medical_department_of_pediatrics-firearm_injury_prevention-November15.zi

#110 : Diagnostic Approach and Clinical Recommendations for Non-obstructive Azoospermia: Global Andrology Forum Survey Results

Background and Aims: Non-obstructive azoospermia (NOA) is the most common form of male infertility, characterized by an absence of sperm in ejaculate and is caused by testicular failure. While NOA afflicts 10-38.3% of infertile males, there is no specific recommendations in EAA/EAU guidelines on its clinical diagnosis or WHO guidelines on semen analysis. Therefore, we conducted a global survey to assess the standard approach of practitioners in the diagnosis and management of NOA. Method: The Global Andrology Forum (GAF) conducted a survey on 436 independent practicing entities from 55 countries. We compiled data from 336 respondents (andrologists, urologists, fertility specialists). Information collected included frequency of NOA, varicocele, frequency of obtaining semen, interval between obtaining semen samples, hormone evaluation (FSH, LH, prolactin, total/free testosterone, SHBG, estradiol, inhibin), genetic testing (karyotype, Y-chromosome deletion, CFTR, Kal1) and referral to genetic counsellors. Results: The majority of participants (80%) either reported <10% or 10-25% NOA frequency in their population (Fig. 1A). 40.6% of participants stated that 10-25% of men with NOA cases have a clinically significant varicocele (Fig. 1B). For NOA diagnosis, majority of participants cited the requirement of at least two semen samples, with a period of 14-29 days as the interval between two semen analyses. To achieve high-quality semen, consideration must be given to an abstinence period (2-7days) and the complete collection of ejaculates. The survey reported FSH (97%), LH (86.9%) and total testosterone (92.9%) tests as most frequently used for NOA patients (Fig. 2A). The initial hormonal evaluation of a patient with suspected NOA should include total testosterone levels and LH, as these hormones are the primary regulators of spermatogenesis. Karyotype analysis (86.2%), Y-microdeletion (88.3%), CFTR (21.9%) and Kal1 (2.7%) were most routinely performed genetic tests (Fig. 2B). Referrals to genetic counsellors is recommended as these defects have the potential to be passed to future generations. Conclusion: This global study evaluates NOA frequency, clinical diagnosis and management by specialists, in an effort to fill the gap in NOA research. Concomitantly, we provide GAF expert recommendations to enhance our collective understanding of NOA, optimize patient care and improve the management of NOA

#108 : Methods of Sperm DNA Fragmentation (SDF) Testing and Interpretation: Results from the Global Andrology Forum Survey

Background and Aims: Sperm DNA fragmentation (SDF) is caused by apoptosis, oxidative stress or incomplete chromatin maturation and can result in male infertility and poor reproductive outcomes. Despite growing trends, there are no specific recommendations on specific diagnostic tests used, assay cut-offs or abstinence periods prior to SDF testing. Therefore, we conducted a global survey to evaluate the approaches used to diagnose SDF, towards a consensus in the field of SDF research and clinical management. Method: The survey collected cross-sectional global data from 55 countries following the CHERRIES protocol. 436 respondents included clinicians, researchers and reproductive biologists from academic, public and private health sectors, all of whom utilize SDF testing in their routine patient care and practice (Fig. 1). Results: Survey results showed that TUNEL (28.6%), SCSA (24.1%), SCD (19.1%) and Comet (5.3%) were most frequently used to diagnose SD (Fig. 2A). Assays were chosen primarily due to their availability (70.0%), cost (44.05%) and accuracy (35.48%). Published evidence on assays (25.71%), training of staff (25.48%), cost to patients (21.67%), assay time (18.81%), ease of interpretation (18.33%) and performance (17.38%) were taken lesser into consideration when selecting SDF diagnostic tests (Fig. 2B). Assay cut-offs of “30% or higher” (33.7%) were most frequently used to diagnose SDF (Fig. 2C). Finally, an abstinence period of 3-5 days was mostly recommended (53.6%; Fig. 2D). The results of this survey provide valuable data on SDF assays used in clinical practice as well as factors affecting assay choices such as availability of resources, personnel and complexity in assay processing. As decreased abstinence period is associated with lower SDF, testing is recommended with an abstinence period of less than five days. We observed that there was a lack of standard cut-off values, and every laboratory should establish its own reference values based on predictive values for fertility outcomes. Conclusion: We present new data associated with SDF testing in real-world practice, on a global scale. The trends and conclusions derived from the study are recommended for inclusion into the 6[Formula: see text] Edition WHO Manual, towards optimized patient care

Sustainable management of municipal solid waste through waste-to-energy technologies

Increasing municipal solid waste (MSW) generation and environmental concerns have sparked global interest in waste valorization through various waste-to-energy (WtE) to generate renewable energy sources and reduce dependency on fossil-derived fuels and chemicals. These technologies are vital for implementing the envisioned global "bioeconomy" through biorefineries. In light of that, a detailed overview of WtE technologies with their benefits and drawbacks is provided in this paper. Additionally, the biorefinery concept for waste management and sustainable energy generation is discussed. The identification of appropriate WtE technology for energy recovery continues to be a significant challenge. So, in order to effectively apply WtE technologies in the burgeoning bioeconomy, this review provides a comprehensive overview of the existing scenario for sustainable MSW management along with the bottlenecks and perspectives.Kartik Popat, Zeel Patel, and Shaili Vyas are grateful to the authorities of GPCB for allowing them to undergo an internship with “A scheme on Project, Thesis or Internship at GPCB”. The authors would like to thank Gujarat Pollution Control Board for encouragement and support during manuscript preparation. M.T. and S.S.L. would like to acknowledge the support by the Ministry of Higher Education, Malaysia under the Higher Institution Centre of Excellence (HICoE), Institute of Tropical Aquaculture and Fisheries (AKUATROP) program (Vot. No. 63933 & Vot. No. 56051, UMT/CRIM/2-2/5 Jilid 2 (10) and Vot. No. 56052, UMT/CRIM/2-2/5 Jilid 2 (11)). M.T. and M.A. would like to extend their sincere appreciation to the University of Tehran and the Biofuel Research Team (BRTeam) for their support throughout this project.Peer reviewe

Autoimmune Lymphoproliferative Syndrome: an Update and Review of the Literature

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by immune dysregulation due to a defect in lymphocyte apoptosis. The clinical manifestations may be noted in multiple family members and include lymphadenopathy, splenomegaly, increased risk of lymphoma and autoimmune disease, which typically involve hematopoietic cell lines manifesting as multilineage cytopenias. Since the disease was first characterized in the early 1990s, there have been many advances in the diagnosis and management of this syndrome. The inherited genetic defect of many ALPS patients has involved (FAS) pathway signaling proteins, but there remain those patients who carry undefined genetic defects. Despite ALPS having historically been considered a primary immune defect presenting in early childhood, adult onset presentation is increasingly becoming recognized, and more so in genetically undefined patients and those with somatic FAS mutations. Thus, future research may identify novel pathways and/or regulatory proteins important in lymphocyte activation and apoptosis