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Jonathan Chatzkel,1 Mayer Fishman,2 Brian Ramnaraign,1 Padraic O’Malley,3 Guru P Sonpavde4 1Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, FL, USA; 2University of South Florida, Tampa, FL, USA; 3Department of Urology, University of Florida, Gainesville, FL, USA; 4AdventHealth Cancer Institute, Orlando, FL, USACorrespondence: Jonathan Chatzkel, Department of Medicine, University of Florida, Box 100278, Gainesville, Orlando, FL, 32610, USA, Email Jonathan.chatzkel@medicine.ufl.eduAbstract: The treatment paradigm for high risk localized and advanced kidney cancer has been characterized by ongoing changes, with the introduction of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) and later with immune checkpoint blockade. In this article, we review how current evidence informs our decision-making on post-checkpoint inhibitor systemic therapies, the role of adjuvant and/or neoadjuvant therapies, and the role of cytoreductive nephrectomy in the evolving systemic therapy landscape. While some studies support a post-checkpoint inhibitor benefit from the VEGFR TKIs cabozantinib or axitinib, the benefit of doublet therapies including a VEGF receptor inhibitor and a checkpoint inhibitor remains an area of active investigation, with the combination of lenvatinib plus pembrolizumab showing promise but with a Phase III trial of the combination of atezolizumab plus cabozantinib showing no benefit over cabozantinib alone. The role of adjuvant therapy in patients with high-risk disease who have undergone cytoreductive nephrectomy and potentially metastasectomy is also an area of continuing interest. While the S-TRAC study demonstrated a disease-free survival benefit for adjuvant sunitinib, no overall survival benefit was shown, and multiple other studies of adjuvant VEGFR TKI therapy have been negative. Subsequently, adjuvant pembrolizumab has shown a benefit in overall survival, whereas trials of neoadjuvant and adjuvant nivolumab, adjuvant atezolizumab, and adjuvant ipilimumab plus nivolumab have all been negative. Finally, the role for cytoreductive nephrectomy continues to be an area of active debate. The CARMENA study raised important questions about the role of cytoreductive nephrectomy given the advances in VEGFR TKI therapy but was characterized by accrual difficulties and a significant number of patients not receiving treatment according to the study protocol. Two ongoing studies (NORDIC-SUN and PROBE) seek to further address the role of cytoreductive nephrectomy in the doublet therapy era.Keywords: kidney cancer, cytoreductive nephrectomy, immunotherapy, adjuvant therapy

Xenotransplantation, transplantation into humans of vascularized organs or viable cells from nonhuman species, is a potential solution to shortages of transplantable human organs. Among challenges to application of clinical xenotransplantation are unknown risks of transmission of animal microbes to immunosuppressed recipients or the community. Experience in allotransplantation and in preclinical models suggests that viral infections are the greatest concern. Worldwide, the distribution of swine pathogens is heterogeneous and cannot be fully controlled by international agricultural regulations. It is possible to screen source animals for potential human pathogens before procuring organs in a manner not possible within the time available for surveillance testing in allotransplantation. Infection control measures require microbiological assays for surveillance of source animals and xenograft recipients and research into zoonotic potential of porcine organisms. Available data suggest that infectious risks of xenotransplantation are manageable and that clinical trials can advance with appropriate protocols for microbiological monitoring of source animals and recipients.

A dysfunctional educational system has been identified as one of the causes of academic dishonesty in the Eastern Europe. This paper describes a case study based on data collected at one Czech university (N = 660) and presents measures that have been taken at the institution after it. The case study combines quantitative self-reported data and qualitative data from students and teachers with hard data from the disciplinary committee. We analyse cases and types of breaches, identify characteristics of students that incline them toward cheating and investigate some of the reasons why. Our research confirms that the inconsistent approach of teachers is a contributing factor to students' propensity to violate academic integrity rules and identifies reasons for such behaviour. Teachers play a key role in prevention, it is their duty to report cases of suspected misconduct, but they need tools to improve the culture of academic integrity. This paper describes in detail the measures which have been at the given faculty as a solution to the identified problem, the authors believe that the presented measures might serve as an inspiration for policymakers on how to tackle the inconsistency of teachers' approaches to student misconduct.

Wei-Bin Shen,1,2 Celine Plachez,2,3 Amanda Chan,4 Deborah Yarnell,1 Adam C Puche,3 Paul S Fishman,1,5 Paul Yarowsky1,21Research Service, VA Maryland Health Care System, Baltimore, MD, USA; 2Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA; 3Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA; 4Notre Dame of Maryland School of Pharmacy, Baltimore, MD, USA; 5Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USAAbstract: Ultrasmall superparamagnetic iron-oxide particles (USPIOs) loaded into stem cells have been suggested as a way to track stem cell transplantation with magnetic resonance imaging, but the labeling, and post-labeling proliferation, viability, differentiation, and retention of USPIOs within the stem cells have yet to be determined for each type of stem cell and for each type of USPIO. Molday ION Rhodamine B™ (BioPAL, Worcester, MA, USA) (MIRB) has been shown to be a USPIO labeling agent for mesenchymal stem cells, glial progenitor cells, and stem cell lines. In this study, we have evaluated MIRB labeling in human neuroprogenitor cells and found that human neuroprogenitor cells are effectively labeled with MIRB without use of transfection reagents. Viability, proliferation, and differentiation properties are unchanged between MIRB-labeled neuroprogenitors cells and unlabeled cells. Moreover, MIRB-labeled human neuroprogenitor cells can be frozen, thawed, and replated without loss of MIRB or even without loss of their intrinsic biology. Overall, those results show that MIRB has advantageous properties that can be used for cell-based therapy.Keywords: ferumoxides, USPIO, MION, neural stem cells, SC121 antibody, human, toxicology

Purpose Since the COVID-19 pandemic, a paediatric network study with clinical sites across Canada suffered a reduction in participation. When research studies fail to meet enrolment targets, it can reduce the strength and validity of the results. This study explores research staff’s experiences of how the COVID-19 pandemic impacted recruitment for a paediatric network study. Methods This study was conducted using a qualitative design. Focus group sessions were used to gain the perspective of research staff involved in recruitment and transcripts were analysed using Colaizzi’s seven-step method of data analysis. Results Analysis revealed four major themes: (1) the COVID-19 pandemic had an impact on research activity; (2) families of children with medical complexity perform a risk-benefit assessment when deciding whether to take part in research; (3) a trusting relationship with clinicians is a key factor in research recruitment; and (4) research needs to be flexible in order to adapt to evolving contexts. Conclusion This study identified both COVID-19 and non-COVID-19-related factors that impacted study recruitment for a paediatric network study. Understanding and addressing these challenges will mitigate the negative impacts on health outcomes that can occur when research studies fail to meet enrolment targets.

Underrepresented students in medicine (URM) have more negative perceptions of the medical school learning environment (LE), a phenomenon that can contribute to higher rates of burnout and attrition in these populations. The hidden curriculum (HC)-defined as a set of values informally conveyed to learners through clinical role-modeling-is a LE socialization construct that has been critically examined for its role in shaping students' professional identities. Yet differences in how URMs and non-URMs experience the HC remain underexplored. The study used a pragmatic approach that drew on elements of grounded theory and employed both deductive and inductive reasoning. Investigators conducted qualitative, semi-structured interviews with a purposive sample of 13 URM and 21 non-URM participants at a Bronx, NY medical school. Interviews examined student experiences and reactions to the HC. Both cohorts witnessed patient disparagement and mistreatment. However, from these encounters, URM participants expressed more moral injury-the adverse emotional consequence of feeling pressured to accept ideologically incongruent values. URMs were also more likely to describe resisting the HC. Differences in group reactions appeared to arise from URMs' identity resonance with patients' lived experiences. Participants across cohorts emphasized increasing URM recruitment as one step toward mitigating these circumstances. URM participants experienced more distress and offered more resistance to the HC relative to non-URMs. The etiology of these differential reactions may stem from relative barriers in negotiating personal and professional identities. As such, URMs' perceptions of the LE may be adversely impacted given their more negative interactions with the HC.

Precision control via molecular structure over adaptive conjugated polymer properties in aqueous environments is critical for realizing their biomedical applications. Here, we unravel the dependence of amphiphilic peptide-polydiacetylene (PDA) conjugate properties on the characteristic steric and hydrophobic contributions within peptide segments that serve as a biomimetic template for diacetylene polymerization in water. We investigated the functional impacts of molecular volume and polarity changes brought by dipeptide substitution domains on the following peptide-PDA material properties at multiple length scales: supramolecular assembly behavior, chain conformation-dependent photophysical properties, cell-material interfacing, and for the first time, bulk electrical properties of their films processed in water. A library of peptide-PDAs with systematically varied sequences show that the contributions of steric effects predominantly influence the electronic structure and resulting trends in photophysical properties, while the interplay between size and hydrophobicity of individual residues becomes more significant for higher-order assemblies affecting bulk properties. This work demonstrates sequence-tunable molecular volume and polarity as synthetic handles to rationally modulate PDA material properties across length scales, providing insights into the programmability of biomimetic conjugated polymers with adaptive functionalities.

Halide perovskites belong to an important family of semiconducting materials with electronic properties that enable a myriad of applications, especially in photovoltaics and optoelectronics. Their optical properties, including photoluminescence quantum yield, are affected and notably enhanced at crystal imperfections where the symmetry is broken and the density of states increases. These lattice distortions can be introduced through structural phase transitions, allowing charge gradients to appear near the interfaces between phase structures. In this work, we demonstrate controlled multiphase structuring in a single perovskite crystal. The concept uses cesium lead bromine (CsPbBr3) placed on a thermoplasmonic TiN/Si metasurface and enables single-, double-, and triple-phase structures to form on demand above room temperature. This approach promises application horizons of dynamically controlled heterostructures with distinctive electronic and enhanced optical properties.

Photons do not carry sufficient momentum to induce indirect opticaltransitions in semiconducting materials such as silicon, necessitating theassistance of lattice phonons to conserve momentum. Compared to direct bandgapsemiconductors, this renders silicon a less attractive material for a widevariety of optoelectronic applications. In this work, we introduce analternative strategy to fulfill the momentum-matching requirement in indirectoptical transitions. We demonstrate that when confined to scales below ~3 nm,photons acquire sufficient momentum to allow electronic transitions at the bandedge of Si without the assistance of a phonon. Confined photons allowsimultaneous energy and momentum conservation in two-body photon-electronscattering; in effect, converting silicon into a direct bandgap semiconductor.We show that this less explored concept of light-matter interaction leads to amarked increase of the absorptivity of Si from the UV to the near-IR. Thestrategy provides opportunities for more efficient use of indirectsemiconductors in photovoltaics, energy conversion, light detection andemission.

Aims: The purpose of this survey study was to examine the demographic and lifestyle factors of women currently in orthopaedic surgery. Methods: An electronic survey was conducted of practising female orthopaedic surgeons based in the USA through both the Ruth Jackson Society and the online Facebook group “Women of Orthopaedics”. Results: The majority of surveyed female orthopaedic surgeons reported being married (76.4%; 285/373) and having children (67.6%; 252/373). In all, 66.5% (247/373) were collegiate athletes; 82.0% (306/373) reported having no female orthopaedic surgeon mentors in undergraduate and medical school. Their mean height is 65.8 inches and average weight is 147.3 lbs. Conclusion: The majority of female orthopaedic surgeons did not have female mentorship during their training. Additionally, biometrically, their build is similar to that of the average American woman. Cite this article: Bone Jt Open 2024;5(5):419–425.

Abstract Objective The aim was to evaluate the role of immune check point inhibitors (ICIs) in patients with high‐grade upper tract urothelial carcinoma (UTUC) who are managed endoscopically when nephroureterectomy (NU) is not feasible, such as in patients who are either not candidates for NU or decline extirpative surgery. Methods All patients diagnosed with high‐grade UTUC and managed endoscopically between January 1996 and August 2022 were included in the study. Subsequently, patients were categorised based on their use of ICIs into group 1 (patients who did not receive ICIs) and group 2 (patients who received ICIs). Survival outcomes were assessed using Kaplan–Meier analysis, while a multivariable regression model was employed to analyse the impact of clinical characteristics on survival. Results A total of 29 patients were enrolled, with 14 in group 1 and 15 in group 2. Both groups exhibited similar demographic and disease characteristics, including multifocality, laterality and initial tumour size. The median follow‐up period was 29.2 months. Notably, group 2 demonstrated significantly enhanced overall and metastasis‐free survival rates compared to group 1. At 47.8 months, the overall survival rate was 0% (all patients died) in group 1, whereas it was 85.7% in group 2. Similarly, the metastasis‐free survival rate was 0% (all patients had metastatic disease) in group 1 at 40.6 months, whereas it reached 78.0% in group 2. The multivariable analysis indicated a correlation between ICI usage and improved survival outcomes, with a hazard ratio of 0.002. Conclusion Utilisation of adjuvant ICIs in the setting of endoscopically treated patients with high‐grade UTUC is associated with significantly improved survival rates. ICIs should be considered in this patient population, however, more studies with larger sample size are warranted.

Sclerosing epithelioid fibrosarcoma is a rare fibrosarcoma variant in which more than half of patients experience local recurrence or metastatic spread. In the current literature, there is limited and nonspecific imaging data, contributing to frequent misdiagnosis and delays in treatment intervention. Given the poor prognosis associated with this malignancy and the high probability of metastases, accurate and prompt diagnoses are critical. In this article, we report the case of a 27-year-old female diagnosed with metastatic sclerosing epithelioid fibrosarcoma following the discovery of a growing palpable mass on her right gluteus maximus muscle. We focus on the use of radiological imaging modalities in optimizing diagnosis and correlate our imaging and pathological findings.

A plasmacytoma is a cancerous growth of abnormal plasma cells that arise within osseous or soft tissue structures. In soft tissue structures, plasmacytomas can present as solitary or multiple masses in the absence of systemic involvement. Solitary plasmacytomas can be subcategorized as extramedullary plasmacytoma (derived from plasma cells located in soft tissues) or osseous plasmacytoma (derived from plasma cells located in the bone marrow). Infrequently, these tumors can arise as extramedullary lesions from the pancreas and present similarly to other tumors, such as pancreatic neuroendocrine tumors (PNETs). In this article, we report the case of a 62-year-old male with a diagnosis of solitary plasmacytoma of the pancreas. We focus on optimizing diagnosis and management through the application of radiological imaging modalities, specifically computed tomography (CT) scans and positron emission tomography-computed tomography (PET-CT) scans.

Abstract The construction materials used in buildings have large and growing implications for global material flows and emissions. Material Intensity (MI) is a metric that measures the mass of construction materials per unit of a building’s floor area. MIs are used to model buildings’ materials and assess their resource use and environmental performance, critical to global climate commitments. However, MI data availability and quality are inconsistent, incomparable, and limited, especially for regions in the Global South. To address these challenges, we present the Regional Assessment of buildings’ Material Intensities (RASMI), a new dataset and accompanying method of comprehensive and consistent representative MI value ranges that embody the variability inherent in buildings. RASMI consists of 3072 MI ranges for 8 construction materials in 12 building structure and function types across 32 regions covering the entire world. The dataset is reproducible, traceable, and updatable, using synthetic data when required. It can be used for estimating historical and future material flows and emissions, assessing demolition waste and at-risk stocks, and evaluating urban mining potentials.

Abstract During embryonic development, pluripotent cells assume specialized identities by adopting particular gene expression profiles. However, systematically dissecting the relative contributions of mRNA transcription and degradation to shaping those profiles remains challenging, especially within embryos with diverse cellular identities. Here, we combine single-cell RNA-Seq and metabolic labeling to capture temporal cellular transcriptomes of zebrafish embryos where newly-transcribed (zygotic) and pre-existing (maternal) mRNA can be distinguished. We introduce kinetic models to quantify mRNA transcription and degradation rates within individual cell types during their specification. These models reveal highly varied regulatory rates across thousands of genes, coordinated transcription and destruction rates for many transcripts, and link differences in degradation to specific sequence elements. They also identify cell-type-specific differences in degradation, namely selective retention of maternal transcripts within primordial germ cells and enveloping layer cells, two of the earliest specified cell types. Our study provides a quantitative approach to study mRNA regulation during a dynamic spatio-temporal response.

Liposarcomas are infrequent malignant tumors of mesenchymal origin most commonly seen in the extremities. Although infrequent, these can develop as primary lesions in the soft tissue of the kidney, making them difficult to diagnose through imaging modalities alone. Primary renal liposarcomas are associated with poor prognoses, increasing the importance of timely and accurate diagnosis. In extremely rare instances, the tumor can arise directly from the fat in the epicenter of the kidney, disguised as an angiomyolipoma. In this article, we report the case of a 54-year-old female who was diagnosed with a well-differentiated liposarcoma of the kidney and underwent radical nephrectomy. Our objective is to evaluate unique radiological imaging findings and correlate with histopathological analysis to optimize diagnosis

The topic of this symposium, capacitating community, invites CLJ readers to consider what makes community possible. This piece showcases one means, small conferences, via a retrospective on the Writing Innovation Symposium (WIS), a regional event with national scope that has hosted writers and writing educators annually in Milwaukee, WI, since 2018. Through a quilted conversation pieced from hours of small-group discussion, twenty-nine participants across academic and nonacademic ranks, roles, and ranges of experience offer insight into the WIS as well as the nature and value of professional community.

Using evidential expressions to indicate one’s source of information for an utterance tends to convey uncertainty on the speaker’s part. Previous accounts of this uncertainty inference attribute it to either extralinguistic reasoning about evidence directness, or to pragmatic reasoning about alternative utterances. Here we present a novel hybrid account, and introduce a set of utterances which allows us to tease apart the three accounts’ predictions. We test these predictions in two studies by manipulating the directness of evidence indicated by an evidential expression. Exp. 1 shows that listeners infer more uncertainty with extreme values of directness. Exp. 2 shows that speakers are more likely to indicate evidence in contexts where the evidence is unreliable. We argue that these findings support an account which involves both extralinguistic and pragmatic reasoning, and develop a formal implementation of such an account within the Rational Speech Act framework.

Aim: A clinical decision support (CDS) tool for metabolic dysfunction-associated steatohepatitis (MASH) was developed to align health systems with clinical guidelines detailed in the MASH Clinical Care Pathway and improve patients’ proactive self-management of their disease. The tool includes a provider-facing web-based application and a mobile application (app) for patients. This protocol outlines a pilot study that will systematically evaluate the implementation of the tool in real-world clinical practice settings. Materials & methods: This implementation research study will use a simultaneous mixed-methods design and is guided by the Consolidated Framework for Implementation Research. The CDS tool for MASH will be piloted for ≥3 months at multiple US-based sites with eligible gastroenterologists and hepatologists (n = 5–10 per site) and their patients (n = 50–100 per site) with MASH or suspected MASH. Each pilot site may choose one or all focus areas within the tool (i.e., risk stratification, screening and referral, or patient care management), based on on-site capabilities. Prior to and at the end of the pilot period, providers and patients will complete quantitative surveys and partake in semi-structured interviews. Outcomes will include understanding the feasibility of implementing the tool in real-world clinical settings, its effectiveness in increasing patient screenings and risk stratification for MASH, its ability to improve provider and patient knowledge of MASH, barriers to adoption of the tool and the tool’s capacity to enhance patient engagement and satisfactionwith their care. Conclusion: Findings will inform the scalable implementation of the tool to ensure patients at risk for MASH are identified early, referred to specialty care when necessary and managed appropriately. Successful integration of the patient app can contribute to better health outcomes for patients by facilitating their active participation in the management of their condition.

IntroductionIn this study, we report a novel therapeutic approach redirecting antigen-specific CD4+ T cells recognizing a hybrid insulin peptide (BDC2.5 T cell receptor (TCR) transgenic CD4+ T cells) to attract and suppress islet-specific CD8+ T cells T cells in the non-obese diabetic (NOD) mouse model, and prevent the development of autoimmune diabetes.MethodsPurified BDC2.5 CD4+ T cells were induced to differentiate into regulatory T cells (Tregs). The Tregs were then electroporated with mRNA encoding chimeric human β2 microglobulin (hβ2m) covalently linked to insulin B chain amino acids 15-23 (designated INS-eTreg) or islet-specific glucose-6-phosphatase related protein (IGRP) peptide 206-214 (designated IGRP-eTreg). Immunoregulatory functions of these engineered regulatory T cells (eTregs) were tested by in vitro assays and in vivo co-transfer experiments with β-cell-antigen-specific CD8+ T cells in NOD.Scid mice or by adoptive transfer into young, pre-diabetic NOD mice.ResultsThese eTregs were phenotyped by flow cytometry, and shown to have high expression of FoxP3, as well as other markers of Treg function, including IL-10. They suppressed polyclonal CD4+ T cells and antigen-specific CD8+ T cells (recognizing insulin or IGRP), decreasing proliferation and increasing exhaustion and regulatory markers in vitro. In vivo, eTregs reduced diabetes development in co-transfer experiments with pathogenic antigen-specific CD8+ T cells (INS-CD8+ or IGRP-CD8+ cells) into NOD.Scid mice. Finally, when the eTreg were injected into young NOD mice, they reduced insulitis and prevented spontaneous diabetes in the recipient mice.ConclusionOur results suggest a novel therapeutic strategy to protect NOD mice by targeting antigen-specific cytotoxic CD8+ T cells, using redirected antigen-specific CD4+ Treg cells, to suppress autoimmune diabetes. This may suggest an innovative therapy for protection of people at risk of development of type 1 diabetes.

ABSTRACT: Background: Successful treatments for intractable chronic low back pain (CLBP) in patients who are not eligible for surgical interventions are scarce. The superior efficacy of differential target multiplexed spinal cord stimulation (DTM SCS) to conventional SCS (Conv-SCS) on the treatment of CLBP in patients with persistent spinal pain syndrome (PSPS) who have failed surgical interventions (PSPS-T2) motivated the evaluation of DTM SCS versus Conv-SCS on PSPS patients who are non-surgical candidates (PSPS-T1). Methods: This is a prospective, open label, crossover, post-market randomized controlled trial in 20 centers across the United States. Eligible patients were randomized to either DTM SCS or Conv-SCS in a 1:1 ratio. Primary endpoint was CLBP responder rate (percentage of subjects with ≥50% CLBP relief) at 3-month in randomized subjects who completed trialing (modified intention-to-treat population). Patients were followed up to 12 months. Secondary endpoints included change of CLBP and leg pain, responder rates, changes in disability, quality of life, patient satisfaction and global impression of change, and safety profile. An optional crossover was available at 6-month to all patients. Results: About 121 PSPS-T1 subjects with CLBP and leg pain mostly associated with degenerative disc disease and radiculopathy and who were not eligible for spine surgery were randomized. CLBP responder rate with DTM SCS (93.5%) was superior to Conv-SCS (36.4%) at the primary endpoint. Superior CLBP responder rates (88.1%–90.5%) were obtained with DTM SCS at all other timepoints. Mean CLBP reduction with DTM SCS (6.52 cm) was superior to that with Conv-SCS (3.01 cm) at the primary endpoint. Similar CLBP reductions (6.23–6.43 cm) were obtained with DTM SCS at other timepoints. DTM SCS provided significantly better leg pain reduction and responder rate, improvement of disability and quality of life, and better patient satisfaction and global impression of change. 90.9% of Conv-SCS subjects who crossed over were CLBP responders at completion of the study. Similar safety profiles were observed between the two groups. Conclusion: DTM SCS for chronic CLBP in nonsurgical candidates is superior to Conv-SCS. Improvements were sustained and provided significant benefits on the management of these patients.

Background: Buprenorphine maintenance treatment remains unavailable in most jails in the US. We provide data on a four-day rapid sublingual buprenorphine (SL-B) induction strategy followed by a weekly dose of extended-release injectable buprenorphine (XR-B) with incarcerated individuals with opioid use disorder (OUD) who were not opioid tolerant. Methods: Between October 2020 to April 2024, N = 65 individuals with an opioid use disorder in jails participating in a larger randomized, controlled trial received SL-B and XR-B prior to release. Primary outcomes included completing the proposed dose induction and any reported adverse events (AEs). Results: Sixty-five individuals received SL-B dose induction from our team’s medical staff, 53 (81.5 %) completed the four-day SL-B dose induction and received their first weekly XR‑B injection on day 5. Of the 65 individuals, 10 (15.38 %) participants reported AEs during the dosing period and/or in the week following the dosing period. All but one of the AEs were rated as mild. One participant experienced a serious adverse event in the week following dose induction. The study medical team determined that this was unlikely to be related to the intervention. Discussion: Overall, our study findings demonstrate the feasibility of implementing a four-day sublingual dose induction followed by a weekly XR-B injection with incarcerated individuals who are not opioid tolerant. This study provides important data to illustrate a dose induction strategy that might assist in reducing illicit diversion in jails, which is a main barrier to buprenorphine delivery cited by correctional administrators.

Abstract The aim of this study is to determine if extended‐release, bioabsorbable, subcutaneous naltrexone (NTX) implants can mitigate respiratory depression after an intravenous injection (IV) of fentanyl. Six different BIOabsorbable Polymeric Implant Naltrexone (BIOPIN) formulations, comprising combinations of Poly‐d,l‐Lactic Acid (PDLLA) and/or Polycaprolactone (PCL‐1 or PCL‐2), were used to create subcutaneous implants. Both placebo and naltrexone implants were implanted subcutaneously in male dogs. The active naltrexone implants consisted of two doses, 644 mg and 1288 mg. A challenge with IV fentanyl was performed in 33 male dogs at 97–100 days after implantation. Following the administration of a 30 μg/kg intravenous fentanyl dose, the placebo cohort manifested a swift and profound respiratory depression with a ~50% reduction in their pre‐dose respiratory rate (RR). The BIOPIN NTX‐implanted dogs were exposed to escalating doses of intravenous fentanyl (30 μg/kg, 60 μg/kg, 90 μg/kg, and 120 μg/kg). In contrast, the dogs implanted with the BIOPIN naltrexone implants tolerated doses up to 60 μg/kg without significant respiratory depression (

The deployment of Li-ion batteries covers a wide range of energy storage applications, from mobile phones, e-bikes, electric vehicles (EV) to stationary energy storage systems. However, safety issue such as thermal runaway is always one of the most important concerns preventing Li-ion batteries from further market penetration. A standardized single-side indentation test protocol was developed to mechanically induce an internal short-circuit. The cell voltage, compressive load, indenter stroke, and temperature at the indentation point are measured in time series. The test data of each cell, along with cell parameters such as dimensions, mass, chemistry, state of charge (SOC), capacity, are integrated to calculate a thermal runaway severity score from 0 to100. Complete data collection process including the original measured record, test method, severity score calculation scheme is presented in this article. The thermal runaway severity analysis and the more than 100 tested Li-ion battery records provide a good data source for further comparison and ranking of thermal runaway risks.