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HumanIslets.com supports diabetes research by offering easy access to islet phenotyping data, analysis tools, and data download. It includes molecular omics, islet and cellular function assays, tissue processing metadata, and phenotypes from 547 donors. As it expands, the resource aims to improve human islet data quality, usability, and accessibility., Competing Interests: Declaration of interests A.L.G.’s spouse is an employee of Genentech and holds stock options in Roche. A.R.P. serves on the Scientific Advisory Committee for Encellin Inc. J.X. is founder of XiaLab Analytics, which provides omics data science training and support., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Etizolam is a thienodiazepine derivative which produces an anxiolytic effect similar to benzodiazepines such as alprazolam (Xanax). Like classic benzodiazepines, etizolam has a high affinity towards the GABA A receptor, and allosterically potentiates the effects of GABA resulting in neuronal hyperpolarization related to chloride influx. When taken in therapeutic doses, etizolam produces a similar effect to Xanax. Counterfeit Xanax tablets contain variable amounts of etizolam. Tablets with high amounts of etizolam can cause toxicity if ingested, especially when combined with other substances. When toxic symptoms occur in patients, they may include severe sedation, unconsciousness, and depression of the medullary respiratory center. In this regard, there is the potential for death. Additionally, the rise in fake Xanax tablets containing etizolam and other counterfeit medications has been exacerbated by the difference in regulations regarding these substances in different countries as well as the illegal drug trade. Healthcare providers may also play a role through the over- or underprescribing of certain medications. Thus, in order to combat the rise in counterfeit medications such as fake Xanax, international cooperation, regulation, and enforcement of laws pertaining to the manufacture, prescription, and distribution of these substances are needed., (© 2024. The Author(s).)

Population-level variation and mechanisms behind insulin secretion in response to carbohydrate, protein, and fat remain uncharacterized. We defined prototypical insulin secretion responses to three macronutrients in islets from 140 cadaveric donors, including those with type 2 diabetes. The majority of donors' islets exhibited the highest insulin response to glucose, moderate response to amino acid, and minimal response to fatty acid. However, 9% of donors' islets had amino acid responses, and 8% had fatty acid responses that were larger than their glucose-stimulated insulin responses. We leveraged this heterogeneity and used multi-omics to identify molecular correlates of nutrient responsiveness, as well as proteins and mRNAs altered in type 2 diabetes. We also examined nutrient-stimulated insulin release from stem cell-derived islets and observed responsiveness to fat but not carbohydrate or protein-potentially a hallmark of immaturity. Understanding the diversity of insulin responses to carbohydrate, protein, and fat lays the groundwork for personalized nutrition., Competing Interests: Declaration of interests A.L.G. declares that her spouse holds stock options in Roche and is an employee of Genentech., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Comprehensive molecular and cellular phenotyping of human islets can enable deep mechanistic insights for diabetes research. We established the Human Islet Data Analysis and Sharing (HI-DAS) consortium to advance goals in accessibility, usability, and integration of data from human islets isolated from donors with and without diabetes at the Alberta Diabetes Institute (ADI) IsletCore. Here we introduce HumanIslets.com, an open resource for the research community. This platform, which presently includes data on 547 human islet donors, allows users to access linked datasets describing molecular profiles, islet function and donor phenotypes, and to perform various statistical and functional analyses at the donor, islet and single-cell levels. As an example of the analytic capacity of this resource we show a dissociation between cell culture effects on transcript and protein expression, and an approach to correct for exocrine contamination found in hand-picked islets. Finally, we provide an example workflow and visualization that highlights links between type 2 diabetes status, SERCA3b Ca 2+ -ATPase levels at the transcript and protein level, insulin secretion and islet cell phenotypes. HumanIslets.com provides a growing and adaptable set of resources and tools to support the metabolism and diabetes research community., Competing Interests: Declaration of Interests ALG’s spouse is an employee of Genentech and holds stock options in Roche AP serves on the Scientific Advisory Committee for Encellin Inc. JX is founder of XiaLab Analytics, which provides omics data science training and support. All other authors confirm no relevant interests to declare.

Tuberculosis remains one of the most significant bacterial infections plaguing the medical community worldwide. The bacteria Mycobacterium tuberculosis retains the ability to manifest as an active infection, latent infection, miliary infection, or reactivation of latent infections in times of immunosuppression. Therefore, the medication regimen to treat the condition revolves around four medications, each with a mechanism that targets a different part of the bacteria. Isoniazid weakens the cell wall but produces neuropathy and hepatotoxicity as side effects. Rifampin interrupts protein synthesis but creates the opportunity for many drug-to-drug interactions and red-orange discolorations as side effects. Pyrazinamide is poorly understood, but it is believed to acidify the internal environment of the bacteria, with gout exacerbations and arthralgias as major side effects. Ethambutol also works as a bacteriostatic medication to interrupt the cell membrane; however, its mechanism is poorly understood. The most concerning side effect is optic neuropathy. The unfavorable side effect profile for tuberculosis treatment may contribute to the higher rates of medication noncompliance with therapy and needs to be addressed in the future., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Jones et al.)

Purpose: Primary central nervous system (CNS) tumors are the second most common cancer in children and adolescents, leading to premature death and disability. Population-based survival estimates aid decision-making in cancer control, however data on survival for primary CNS tumors in Latin America is lacking. We describe survival rates for children with primary CNS tumors treated in ten Colombian cities., Methods: We analyzed data from children and adolescents newly diagnosed with cancer between 2012 and 2021, participating in the Childhood Cancer Clinical Outcomes Surveillance System (VIGICANCER) in ten cities in Colombia. VIGICANCER collects information on clinical outcomes from twenty-seven pediatric oncology units and conducts active follow-up every three months. VIGICANCER does not register craniopharyngiomas; we excluded intracranial germ cell tumors for this report. We used the Kaplan-Meier method to estimate the overall survival probability, stratified by sociodemographic variables, topography, WHO grading, receipt of radiation therapy, and type of surgical resection. We analyzed the prognostic capacity of variables using multivariate proportional Cox's regression, stratified by city and year of diagnosis., Results: During the study period, VIGICANCER included 989 primary CNS tumors in 879 children and 110 adolescents. The cohort median age was 9 years; 53% of patients were males, and 8% were Afro-descendants. Most common tumors were supratentorial astrocytomas (47%), astrocytic tumors (35%), medulloblastomas (20%), ependymomas (11%), and mixed and unspecified gliomas (10%). Five-year overall survival of the entire cohort was 54% (95% CI, 51-58); for supratentorial gliomas, WHO grade I was 77%, II was 62%, III-IV was 27%, respectively, and for medulloblastoma was 61%. The adjusted hazard rate ratio for patients with WHO grade III and IV, for those with subtotal resection, for brainstem location, and for those not receiving radiation therapy was 7.4 (95% CI, 4.7-11.8), 6.4 (95% CI, 4.2-9.8), 2.8 (95% 2.1-3.8), 2.0 (95% CI, 1.3-2.8) and 2.3 (95% CI, 1.7-3.0), respectively., Conclusion: We found that half of Colombia's children and adolescents with primary CNS tumors survive five years, compared to 70% to 80% in high-income countries. In addition to tumor biology and location, gross total resection was crucial for improved survival in this cohort. Systematic monitoring of survival and its determinants provides empirical data for guiding cancer control policies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ramirez, Piedrahita, Ardila, Pardo, Cabrera-Bernal, Lopera, Suarez, Portilla, Narváez, Rodriguez, Castro, Castro, Estupinan-Perico, Valencia, Álvarez, Fox, Bravo and Aristizabal.)