Mixed rare earth metals production from surface soil in Idaho, USA: Techno-economic analysis and greenhouse gas emission assessment.

Rare earth elements are crucial for the development of cutting-edge technologies in various sectors, such as energy, transportation, and health care. Traditional extraction of rare earth elements from soil and ore deposits primarily involves chemical leaching and solvent extraction. Environmental-based biological rare earth element extraction, such as bioleaching, can be a promising alternative to mitigate pollution and hazardous wastes. We investigated the sustainability aspects (techno-economic and environmental impact) of mixed rare earth metals production from soil in Idaho, USA. We focused on the bioleaching of surface soil using techno-economic analysis and "cradle-to-gate" life cycle assessment. The system boundary included collection, transportation, bioleaching, and molten salt electrolysis. Our results revealed that the mixed rare earth metals (including Nd, Ce, and La) production costs approximately $10,851 per metric ton and generates 1.9 × 106 kg CO2 eq./ton. Our results showed that most emissions are due to energy consumption during bioleaching. Over a 100-year time horizon ultrasound-assisted bioleaching can reduce greenhouse gas emissions by approximately 91 % compared to the traditional bioleaching process by decreasing the organic acid leaching process time and energy consumption. Our work demonstrates that higher solids loading in leaching with biological reactions can promote economic feasibility and reduce chemical wastes.

Neurofibromatosis Type 1: Optimizing Management with a Multidisciplinary Approach.

Neurofibromatosis Type I (NF1) is a complex genetic condition that affects multiple organ systems and presents a unique set of challenges for clinicians in its management. NF1 is a tumor predisposition syndrome that primarily affect the peripheral and central nervous systems via the impact of haploinsufficiency upon neural crest lineage cells including Schwann cells, melanocytes, fibroblasts, etc. NF1 can further lead to pathology of the skin, bones, visual system, and cardiovascular system, all of which can drastically reduce a patient's quality of life (QOL). This review provides a comprehensive examination of the many specialties required for the care of patients with Neurofibromatosis Type 1 (NF1). We delve into the pathogenesis and clinical presentation of NF1, highlighting its diverse manifestations and the challenges they pose in management. The review underscores the importance of a multidisciplinary approach to NF1, emphasizing how such an approach can significantly improve patient outcomes and overall QOL. Central to this approach is the role of the NF expert, who guides a multidisciplinary team (MDT) comprising healthcare professionals from many areas of expertise. The MDT collaboratively addresses the multifaceted needs of NF1 patients, ensuring comprehensive and personalized care. This review highlights the need for further investigation to optimize the workflow for NF1 patients in an MDT setting, and to improve implementation and efficacy.

Dermatologic Manifestations of Neurofibromatosis Type 1 and Emerging Treatments.

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that increases one's risk for both benign and malignant tumors. NF1 affects every organ in the body, but the most distinctive symptoms that are often the most bothersome to patients are the cutaneous manifestations, which can be unsightly, cause pain or pruritus, and have limited therapeutic options. In an effort to increase awareness of lesser-known dermatologic associations and to promote multidisciplinary care, we conducted a narrative review to shed light on dermatologic associations of NF1 as well as emerging treatment options. Topics covered include cutaneous neurofibromas, plexiform neurofibromas, diffuse neurofibromas, distinct nodular lesions, malignant peripheral nerve sheath tumors, glomus tumors, juvenile xanthogranulomas, skin cancer, and cutaneous T-cell lymphoma.

Integrated Drug Mining Reveals Actionable Strategies Inhibiting Plexiform Neurofibromas.

Neurofibromatosis Type 1 (NF1) is one of the most common genetic tumor predisposition syndromes, affecting up to 1 in 2500 individuals. Up to half of patients with NF1 develop benign nerve sheath tumors called plexiform neurofibromas (PNs), characterized by biallelic NF1 loss. PNs can grow to immense sizes, cause extensive morbidity, and harbor a 15% lifetime risk of malignant transformation. Increasingly, molecular sequencing and drug screening data from various preclinical murine and human PN cell lines, murine models, and human PN tissues are available to help identify salient treatments for PNs. Despite this, Selumetinib, a MEK inhibitor, is the only currently FDA-approved pharmacotherapy for symptomatic and inoperable PNs in pediatric NF1 patients. The discovery of alternative and additional treatments has been hampered by the rarity of the disease, which makes prioritizing drugs to be tested in future clinical trials immensely important. Here, we propose a gene regulatory network-based integrated analysis to mine high-throughput cell line-based drug data combined with transcriptomes from resected human PN tumors. Conserved network modules were characterized and served as drug fingerprints reflecting the biological connections among drug effects and the inherent properties of PN cell lines and tissue. Drug candidates were ranked, and the therapeutic potential of drug combinations was evaluated via computational predication. Auspicious therapeutic agents and drug combinations were proposed for further investigation in preclinical and clinical trials.

Human Cytomegalovirus Compromises Development of Cerebral Organoids.

Congenital human cytomegalovirus (HCMV) infection causes a broad spectrum of central and peripheral nervous system disorders, ranging from microcephaly to hearing loss. These ramifications mandate the study of virus-host interactions in neural cells. Neural progenitor cells are permissive for lytic infection. We infected two induced pluripotent stem cell (iPSC) lines and found these more primitive cells to be susceptible to infection but not permissive. Differentiation of infected iPSCs induced de novo expression of viral antigens. iPSCs can be cultured in three dimensions to generate cerebral organoids, closely mimicking in vivo development. Mock- or HCMV-infected iPSCs were subjected to a cerebral organoid generation protocol. HCMV IE1 protein was detected in virus-infected organoids at 52 days postinfection. Absent a significant effect on organoid size, infection induced regions of necrosis and the presence of large vacuoles and cysts. Perhaps more in parallel with the subtler manifestations of HCMV-induced birth defects, infection dramatically altered neurological development of organoids, decreasing the number of developing and fully formed cortical structure sites, with associated changes in the architectural organization and depth of lamination within these structures, and manifesting aberrant expression of the neural marker ß-tubulin III. Our observations parallel published descriptions of infected clinical samples, which often contain only sparse antigen-positive foci yet display areas of focal necrosis and cellular loss, delayed maturation, and abnormal cortical lamination. The parallels between pathologies present in clinical specimens and the highly tractable three-dimensional (3D) organoid system demonstrate the utility of this system in modeling host-virus interactions and HCMV-induced birth defects.IMPORTANCE Human cytomegalovirus (HCMV) is a leading cause of central nervous system birth defects, ranging from microcephaly to hearing impairment. Recent literature has provided descriptions of delayed and abnormal maturation of developing cortical tissue in infected clinical specimens. We have found that infected induced pluripotent stem cells can be differentiated into three-dimensional, viral protein-expressing cerebral organoids. Virus-infected organoids displayed dramatic alterations in development compared to those of mock-infected controls. Development in these organoids closely paralleled observations in HCMV-infected clinical samples. Infection induced regions of necrosis, the presence of larger vacuoles and cysts, changes in the architectural organization of cortical structures, aberrant expression of the neural marker ß-tubulin III, and an overall reduction in numbers of cortical structure sites. We found clear parallels between the pathologies of clinical specimens and virus-infected organoids, demonstrating the utility of this highly tractable system for future investigations of HCMV-induced birth defects.

Response to Disclosure as an Indicator of Competence to Stand Trial.

Ethics guidelines recommend that forensic mental health professionals begin in-person assessments by explaining the nature and purpose of the examination. To learn whether evaluees have understood and can give consent, forensic practitioners may ask evaluees to paraphrase the explanation. This article explores how a forensic evaluee's disclosure response (DR) reveals substantive information relevant to the purposes of a forensic examination. We examined archival data from 255 reports on competence to stand trial (CST) that a Midwest public sector hospital had previously submitted to courts. We classified each evaluee's DR at one of three levels: DR = yes (accurate paraphrasing), DR = no (inability to paraphrase or provide a relevant response), or DR = other (an intermediate level implying a less-than-accurate response). None of the 28 DR = no evaluees was CST, and only 7 (17%) of the 48 DR = other evaluees were CST. Thus, a CST evaluee who cannot paraphrase an examiner's explanation is likely to be incompetent to stand trial, and an examiner would need to adduce a strong argument to support any opinion to the contrary.

Cutaneous features predict paraspinal neurofibromas in neurofibromatosis type 1.

In neurofibromatosis type 1 (NF-1), malignant transformation of internal plexiform neurofibromas carries a poor prognosis, in part because they are not evident clinically. In this issue, Sbidian et al. describe a novel "NF-1Score" equation that employs four easily observable traits to predict the presence of paraspinal neurofibromas. This tool can identify at-risk patients during regular screening to help reduce mortality.