Search

According to the American Counseling Association and the Council for Accreditation of Counseling and Related Educational Programs, social justice advocacy is an ethical imperative for counselors and a training standard for counseling students. As a group of socially conscious mental health counseling students and faculty, we developed and facilitated a social justice advocacy group to learn about tangible ways to engage in social justice action. Using the S-Quad model developed by Toporek and Ahluwalia, we formed and facilitated a social justice advocacy group for our peers. This paper will serve as a reflection of our experiences engaging in the process.

Recurrent high-grade intracranial malignancies have a grim prognosis and uniform management guidelines are lacking. Re-irradiation is underused due to concerns about irreversible side effects. Pulsed-reduced dose rate radiotherapy (PRDR) aims to reduce toxicity while improving tumor control by exploiting dose-rate effects. We share our initial experience with temporally modulated pulsed proton re-irradiation (TMPPR), focusing on workflow, safety, feasibility, and outcomes for the first patient cohort. TMPPR was administered to patients with recurrent or progressive central nervous system malignancies using intensity modulated proton therapy with three fields. Patient and treatment data were collected, responses categorized using RANO assessment, and toxicities graded using CTCAE v5.0. Five patients received TMPPR between October 2022 and May 2023, with a median age of 54 years (Range: 32-72), and a median time from initial radiotherapy to re-RT of 23 months (Range 14-40). Treatment was completed without delay, with a median dose of 60 GyRBE in 30 fractions. Initial treatment response assessment showed complete (n = 1) or partial (n = 3) responses. Limited toxicity was observed, primarily grade 2 alopecia and one case of radiation necrosis graded at 2. This early experience demonstrates the feasibility of TMPPR delivery, highlighting the importance of prospective evaluations in the re-irradiation setting.

Onsite production of gigawatt-scale wind- and solar-sourced hydrogen (H2) at industrial locations depends on the ability to store and deliver otherwise-curtailed H2 during times of power shortages. Thousands of tonnes of H2 will require storage in regions where subsurface storage is scarce, which may only be possible using liquid organic H2 carriers. We evaluate aboveground system with a focus on providing technical insights into toluene/methylcyclohexane (TOL/MCH) storage systems in locations suitable for gigawatt-scale wind- and solar-powered electrolyzer systems in the United States. Here we show that the levelized cost of storage, at a national median of US dollar $1.84/kg-H2 is spatially heterogeneous, causing minor impact on the cost of H2 supply in the Midwest, and significant impact in Central California and the Southeast. While TOL/MCH may be the cheapest aboveground bulk storage solution evaluated, upfront capital costs, modest energy efficiency, reliance on critical materials and pre-sulfided catalysts, and greenhouse gas emissions from heating are opportunities for further development.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P

BACKGROUND: Early palliative/pre-emptive intervention improves clinical outcomes and quality of life for patients with metastatic cancer. A previous signal-seeking randomized controlled trial (RCT) demonstrated that early upfront radiotherapy to asymptomatic or minimally symptomatic high-risk osseous metastases led to reduction in skeletal-related events (SREs), a benefit driven primarily by subgroup of high-risk spine metastasis. The current RCT aims to determine whether early palliative/pre-emptive radiotherapy in patients with high-risk, asymptomatic or minimally symptomatic spine metastases will lead to fewer SREs within 1 year. METHODS: This is a single-center, parallel-arm, in-progress RCT in adults (≥ 18 years) with ECOG performance status 0-2 and asymptomatic or minimally symptomatic (not requiring opioids) high-risk spine metastases from histologically confirmed solid tumor malignancies with > 5 sites of metastatic disease on cross-sectional imaging. High-risk spine metastases are defined by the following: (a) bulkiest disease sites ≥ 2 cm; (b) junctional disease (occiput to C2, C7-T1, T12-L2, L5-S1); (c) posterior element involvement; or (d) vertebral body compression deformity > 50%. Patients are randomized 1:1 to receive either standard-of-care systemic therapy (arm 1) or upfront, early radiotherapy to ≤ 5 high-risk spine lesions plus standard-of-care systemic therapy (arm 2), in the form of 20-30 Gy of radiation in 2-10 fractions. The primary endpoint is SRE, a composite outcome including spinal fracture, spinal cord compression, need for palliative radiotherapy, interventional procedures, or spinal surgery. Secondary endpoints include (1) surrogates of health care cost, including the number and duration of SRE-related hospitalizations; (2) overall survival; (3) pain-free survival; and (4) quality of life. Study instruments will be captured pre-treatment, at baseline, during treatment, and at 1, 3, 6, 12, and 24 months post-treatment. The trial aims to accrue 74 patients over 2 years to achieve > 80% power in detecting difference using two-sample proportion test with alpha

Audience: This is an in-person escape room and procedure simulation activity based on complications of human immunodeficiency virus (HIV) in India, which was created by using local HIV management guidelines. Emergency Medicine (EM) trainees of all post-graduate levels are the target audience. This may also be used by trainees in other specialties, such as infectious disease or internal medicine, who require an understanding of HIV and its complications. This escape room can be completed in teams of varying sizes and is designed to be adaptable to local resource availability.Background: Patients with HIV present to the Emergency Department (ED) for a variety of reasons such as initial viral syndrome, medication side effects, and opportunistic infections. While the widespread use of antiretroviral therapy (ART) has significantly increased the life expectancy of patients living with HIV and decreased the incidence of classical opportunistic infections, EM providers should still be vigilant and competent in diagnosing and managing these pathologies. This is particularly critical in India, where the prevalence of HIV was most recently estimated at 0.22% (2.2 million people older than 15 years) in 2020.1 This patient population, primarily infected through unprotected heterosexual contact, is at high risk for interruptions in ART and development of opportunistic infections for a variety of reasons including migration for work, low social status of women, and significant social stigma against HIV.2 Simulation is an educational opportunity to review these high-acuity low-occurrence presentations to prepare EM trainees for independent practice.Educational Objectives: By the end of the escape room, learners should be able to: 1) describe the mechanism of action of antiretroviral therapies available in India, 2) prescribe initial antiretroviral therapy to a patient presenting to the emergency department with a new diagnosis of HIV, 3) develop a differential diagnosis for a patient with HIV presenting to the ED with chest pain, 4) identify common dermatologic manifestations of opportunistic infections in patients with HIV, 5) identify computerized tomography scan and lumbar puncture features for central nervous system infections seen in patients with Acquired Immunodeficiency Syndrome (AIDS), 6) identify red flag features and appropriate workup for a patient with HIV presenting with a headache to the ED, 7) interpret images obtained during a Rapid Ultrasound for Shock and Hemorrhage (RUSH) exam, 8) identify cardiac tamponade and perform a pericardiocentesis, and 9) communicate and collaborate as a team to manage a complex, unstable patient with HIV in the ED.Educational Methods: We sought to create and implement an educational tool that could meet the complex education needs of EM trainees while being low cost, easily adapted to local resources, and engaging for trainees. Hospitals participating in the Masters in Emergency Medicine (MEM) program, a global partnership between the Ronald Reagan Institute for Emergency Medicine at the George Washington University and 18 hospitals in India, have resource variability for traditional simulation. The escape room created combines simulation, content review specific to the contextual practice of EM in India focused on HIV and its complications, and critical procedure teaching on pericardiocentesis. This innovation framework is based on Kolb’s experiential learning cycle and incorporates the gamification principles of a sense of autonomy, perception of competitiveness, and learner-relatedness.3-4 Escape rooms have been shown to engage learners, and low-fidelity procedure models could further maximize the experience for learners in resource variable settings.5 A pericardiocentesis model was adapted from Lord et al.’s low-fidelity model, ensuring it could be assembled with materials readily available in-country.6Research Methods: We adapted the escape room format to combine simulation, content review, and procedural training in a cost-effective, contextually relevant, and scalable way. The escape room was trialed using a case of chest pain and altered mental status caused by a pericardial effusion due to tuberculosis in a patient with HIV. Local practice patterns and guidelines were used to develop puzzles and clinical clues. A pericardiocentesis model was constructed using materials readily available in India. Pre- and post-surveys were developed to assess baseline trainee experience with escape rooms, self-reported knowledge of the differential diagnosis and management for altered mental status, and ways to incorporate escape room content into daily practice.Results: A total of 47 trainees participated; 41 of 47 participants completed both pre- and post-surveys (87% response rate). Participants represented all program trainee levels: 49% (n = 20) PGY-1, 27% (n = 11) PGY-2, and 24% (n = 10) PGY-3. Based on a score greater than seven on a 1-10 Likert scale, the escape room was rated as “highly effective” by 93.5% of respondents in reviewing medical knowledge. The trainees were allotted 60 minutes to escape the room; the median time for escape room completion was 57 minutes. The escape room and pericardiocentesis model cost under $100 USD, were repeated up to six times in one day, and could be recycled for future use.Discussion: Utilizing simulation in the escape room format that can be adaptable to variable resource settings is a valuable educational tool. The integrated escape room and procedure training proved to be an effective educational tool that was scalable and maintained efficacy across variable hospital resource levels. The next step includes adapting this format for other disease pathologies. This is a useful way to meet the education needs of MEM program trainees, regardless of hospital resource availability, that could be replicable in other EM training programs.

Implementation of standardized protocols in neurooncology during the surgical resection of brain tumors is needed to advance the clinical treatment paradigms that use tissue for diagnosis, prognosis, bio-banking, and treatment. Currently recommendations on intraoperative tissue procurement only exist for diffuse gliomas but management of other brain tumor subtypes can also benefit from these protocols. Fresh tissue from surgical resection can now be used for intraoperative diagnostics and functional precision medicine assays. A multidisciplinary neuro-oncology perspective is critical to develop the best avenues for practical standardization. This perspective from the multidisciplinary Oncology Tissue Advisory Board (OTAB) discusses current advances, future directions, and the imperative of adopting standardized protocols for diverse brain tumor entities. There is a growing need for consistent operating room practices to enhance patient care, streamline research efforts, and optimize outcomes.

Audience: This case-based virtual escape room (VER) serves as a didactic activity suitable for learners who require an understanding of organophosphate toxicity. Educators may use this VER for distance-based learning in settings with adequate internet access.Introduction:India faces a concerning escalation in suicide rates, particularly among teenagers and young adults, often involving intentional pesticide ingestion, notably organophosphates.1-3 Our project addresses organophosphate ingestion by using a VER, a virtual learning platform adapted from in-person escape rooms to engage participants for educational purposes.4,5 Demonstrating success in medical, pharmacy, and nursing education, VERs increased satisfaction and competency among healthcare trainees compared to traditional learning platforms while fostering teamwork and communication in a virtual learning environment.6,7Educational Objectives:By the end of the activity, learners should be able to: 1) recognize risk factors, symptoms, and presentation for organophosphate poisoning; 2) understand the radiologic and laboratory findings in organophosphate poisoning; 3) distinguish and differentiate electrocardiogram findings in common toxic ingestions; 4) explain the pathophysiology of organophosphate poisoning; 5) understand the importance of decontamination of the patient and personal protective equipment for staff for organophosphate poisoning; 6) describe the airway management of organophosphate poisoning; 7) describe the medical management of organophosphate poisoning, including antidotes and the correct dosing and 8) demonstrate teamwork through communication and collaboration.Educational Methods: The development process involved a seven-step approach, beginning with topic selection. The process involved creating a scenario, defining learning objectives, and designing an appropriate room. Clues and puzzles were tailored to align with the learning objectives and promote interactivity. The VER was hosted on Google Sites (Google LLC), accompanied by a facilitator guide offering content and technical support.Research Methods: This VER leverages technology for distance learning, using Zoom (Zoom Video Communications Inc.) for online sessions with EM trainees. Participants were organized into small groups in breakout rooms on Zoom, following a structured format that included a pre-briefing, a timed escape room scenario, debriefing, and evaluation. Afterward, an evaluation in the format of a survey was distributed to participants. This study was Institutional Review Board exempt.Results: Out of 120 participants in the VER, 50% responded to a survey. The majority found the activity interactive, engaging, and exciting. This feedback indicated a positive reaction to the VER, consistent with the Kirkpatrick model's first level of assessment.8 The VER effectively promoted learning and reinforced clinical knowledge, contributing to the second level of the Kirkpatrick model. In this case, 84.7% of respondents were able to identify knowledge gaps, and 84.2% of respondents found this to be a feasible model to reinforce medical knowledge.Discussion: This innovative VER addresses the value of distance-based learning in any setting with an internet connection. It has successfully enhanced collaboration and communication among participants in small groups, making it a valuable resource for medical education. This study has several limitations worth noting including a relatively low survey response rate. Baseline data was not collected prior to the VER. Additionally, the VER was not designed to be an open-book assessment; however, the absence of an in-person moderator makes it challenging to ascertain whether participants used external resources. Furthermore, the exclusive focus of this VER on a single topic may diminish its overall use compared to more traditional didactic sessions. This study is also limited by lack of long-term outcome data. Future studies could further assess knowledge improvement and clinical application. The authors plan to develop additional case-based VERs to advance EM trainees' knowledge, skills, and communication. Overall, the VER offers a promising and free educational tool for distance learning with potential benefits for various settings with internet access.

While significant advances have been made and early commercial fuel cell light-duty vehicles (LDVs) are starting to be produced, fuel cells in the heavy-duty-vehicle (HDV) transportation sector (including trucks, long-haul semitrailers, maritime, trains, etc.) are nascent, despite the fact that advantages of fuel cells compared to both diesel and electric powertrains are very compelling in terms of emissions, charging time, efficiency, power-to-weight ratio, among others. However, the fuel-cell technology for HDVs requires a paradigm shift in fuel-cell research and development compared to LDVs, where the emphasis becomes efficiency and improvements in durability instead of a focus on increased power densities and lower cell costs. Heavy-duty applications require significantly longer vehicle lifetimes (>25,000 hours/1,000,000 miles for heavy-duty trucks), and therefore require improved fuel cell durability compared to light-duty vehicles. In 2020, HFTO formed the Million Mile Fuel Cell Truck Consortium (M2FCT) that includes a core team of five national laboratories to overcome durability and efficiency challenges in PEMFCs for heavy-duty applications with an initial focus on long-haul trucks. While targets and testing protocols have been developed for light-duty vehicles, the same level of targets and testing protocols have not been established for heavy-duty transportation. With operational times of greater than > 25,000 hours required, the need for well-developed accelerated stress tests (ASTs) is amplified. Results from these ASTs demonstrate the need for more durable electrode layers and well-controlled potential variations. This presentation will provide an overview of the DOE’s Fuel Cell R&D approach, highlighting past and current activities, as well as strategies to enable fuel cell competiveness for heavy-duty applications. Acknowledgments This work was funded through the DOE M2FCT Consortium with thanks to DOE EERE HFTO, Fuel Cell Technologies Office. Team Leader: Dimitrios Papageoropoulos and Technical Development Manager: Greg Kleen.

Abstract Trastuzumab-deruxtecan (T-DXd) has demonstrated intracranial efficacy; however, safety and efficacy data remains limited with stereotactic radiosurgery (SRS). A multi-institutional review was performed with HER2+ or HER2-low metastatic breast cancer treated with T-DXd and SRS for active brain metastases. We identified 215 lesions treated over 48 SRS courses in 34 patients. Median follow up from T-DXd initiation was 13.9 months. The cumulative incidence of symptomatic radiation necrosis at 24 months per lesion was 2.1% and per patient 11%. The 12-month LC was 97%. HER2-low was associated with worse distant intracranial control (DIC) (adjusted HR 2.5, 95% CI 1.1–5.6, p = 0.03) and worse systemic progression free survival (PFS) (HR 4.1, 95% CI 1.6–10.7, p = 0.004). Concurrent SRS and T-DXd has excellent local control, without an increased risk of radiation necrosis. HER2-low disease is associated with worse systemic PFS and DIC with T-DXd compared to HER2+.

Abstract Whole-exome sequencing (WES), a ground-breaking technology, has emerged as a linchpin in neurology and neurosurgery, offering a comprehensive elucidation of the genetic landscape of various neurological disorders. This transformative methodology concentrates on the exonic portions of DNA, which constitute approximately 1% of the human genome, thus facilitating an expedited and efficient sequencing process. WES has been instrumental in advancing our understanding of neurodegenerative diseases, neuro-oncology, cerebrovascular disorders, and epilepsy by revealing rare variants and novel mutations and providing intricate insights into their genetic complexities. This has been achieved while maintaining a substantial diagnostic yield, thereby offering novel perspectives on the pathophysiology and personalized management of these conditions. The utilization of WES boasts several advantages over alternative genetic sequencing methodologies, including cost-effectiveness, reduced incidental findings, simplified analysis and interpretation process, and reduced computational demands. However, despite its benefits, there are challenges, such as the interpretation of variants of unknown significance, cost considerations, and limited accessibility in resource-constrained settings. Additionally, ethical, legal, and social concerns are raised, particularly in the context of incidental findings and patient consent. As we look to the future, the integration of WES with other omics-based approaches could help revolutionize the field of personalized medicine through its implications in predictive models and the development of targeted therapeutic strategies, marking a significant stride toward more effective and clinically oriented solutions. Graphical Abstract

Abstract Recurrent high-grade intracranial malignancies have a grim prognosis and uniform management guidelines are lacking. Re-irradiation is underused due to concerns about irreversible side effects. Pulsed-reduced dose rate radiotherapy (PRDR) aims to reduce toxicity while improving tumor control by exploiting dose-rate effects. We share our initial experience with temporally modulated pulsed proton re-irradiation (TMPPR), focusing on workflow, safety, feasibility, and outcomes for the first patient cohort. TMPPR was administered to patients with recurrent or progressive central nervous system malignancies using intensity modulated proton therapy with three fields. Patient and treatment data were collected, responses categorized using RANO assessment, and toxicities graded using CTCAE v5.0. Five patients received TMPPR between October 2022 and May 2023, with a median age of 54 years (Range: 32–72), and a median time from initial radiotherapy to re-RT of 23 months (Range 14–40). Treatment was completed without delay, with a median dose of 60 GyRBE in 30 fractions. Initial treatment response assessment showed complete (n = 1) or partial (n = 3) responses. Limited toxicity was observed, primarily grade 2 alopecia and one case of radiation necrosis graded at 2. This early experience demonstrates the feasibility of TMPPR delivery, highlighting the importance of prospective evaluations in the re-irradiation setting.

Introduction This study aimed to evaluate the usefulness of machine learning (ML) and neural network (NN) models versus traditional statistical methods for estimating biochemical recurrence (BCR) in men following robot-assisted radical prostatectomy (RARP). Methods Patients who underwent RARP from November 2011 to July 2022 were taken in the study. Patients with BCR were assigned to Group 2, whereas those without BCR were placed in Group 1. Preoperative and postoperative parameters, together with demographic data, were recorded in the database. This study used one NN, the radial basis function NN (RBFNN), and two ML approaches, the K-nearest neighbor and XGboost ML models, to predict BCR. Results Following the application of exclusion criteria, 516 patients were deemed eligible for the study. Of those, 234 (45.3%) developed BCR, and 282 (54.7%) did not. The results showed that the median follow-up period was 24 (15–42) months, and the median BCR diagnosis was 12.23 ± 15.58 months. The area under the curve (AUC) for the Cox proportional hazard analysis was 0.77. The receiver-operating characteristic curves (AUCs) for the XGBoost and K closest neighbor models were 0.82 and 0.69, respectively. The RBFNN’s AUC was 0.82. Conclusions The classical statistical model was outperformed by XGBoost and RBFNN models in predicting BCR.

Abstract Obesity is associated with dysfunctional electrocardiographic and cardiac autonomic parameters, which may lead to increased cardiovascular morbidity. Novel electrocardiographic repolarization markers such as Tpeak-Tend (Tpe) interval have not yet been deeply studied in obese patients. We aimed to investigate the association between ventricular repolarization parameters and heart rate variability (HRV) and how they are affected by changes occurring in the cardiac autonomic nervous system. Ninety subjects categorized by Southeast Asian BMI (kg/m2) standards - normal (18-22.9), overweight (23-24.9), and obese (> 24.9), underwent assessment of ventricular repolarization parameters and HRV. Linear correlation between different parameters was also conducted. Obese subjects exhibited longer QTc and Tpe intervals compared to normal-weight subjects (p-value

Abstract Background It is well-known that nanoparticles sediment, diffuse and aggregate when dispersed in a fluid. Once they approach a cell monolayer, depending on the affinity or “stickiness” between cells and nanoparticles, they may adsorb instantaneously, settle slowly – in a time- and concentration-dependent manner - or even encounter steric hindrance and rebound. Therefore, the dose perceived by cells in culture may not necessarily be that initially administered. Methods for quantifying delivered dose are difficult to implement, as they require precise characterization of nanoparticles and exposure scenarios, as well as complex mathematical operations to handle the equations governing the system dynamics. Here we present a pipeline and a graphical user interface, DosiGUI, for application to the accurate nano-dosimetry of engineered nanoparticles on cell monolayers, which also includes methods for determining the parameters characterising nanoparticle-cell stickiness. Results We evaluated the stickiness for 3 industrial nanoparticles (TiO2 – NM-105, CeO2 – NM-212 and BaSO4 – NM-220) administered to 3 cell lines (HepG2, A549 and Caco-2) and subsequently estimated corresponding delivered doses. Our results confirm that stickiness is a function of both nanoparticle and cell type, with the stickiest combination being BaSO4 and Caco-2 cells. The results also underline that accurate estimations of the delivered dose cannot prescind from a rigorous evaluation of the affinity between the cell type and nanoparticle under investigation. Conclusion Accurate nanoparticle dose estimation in vitro is crucial for in vivo extrapolation, allowing for their safe use in medical and other applications. This study provides a computational platform – DosiGUI – for more reliable dose-response characterization. It also highlights the importance of cell-nanoparticle stickiness for better risk assessment of engineered nanomaterials.

Abstract Onsite production of gigawatt-scale wind- and solar-sourced hydrogen (H2) at industrial locations depends on the ability to store and deliver otherwise-curtailed H2 during times of power shortages. Thousands of tonnes of H2 will require storage in regions where subsurface storage is scarce, which may only be possible using liquid organic H2 carriers. We evaluate aboveground system with a focus on providing technical insights into toluene/methylcyclohexane (TOL/MCH) storage systems in locations suitable for gigawatt-scale wind- and solar-powered electrolyzer systems in the United States. Here we show that the levelized cost of storage, at a national median of US dollar $1.84/kg-H2 is spatially heterogeneous, causing minor impact on the cost of H2 supply in the Midwest, and significant impact in Central California and the Southeast. While TOL/MCH may be the cheapest aboveground bulk storage solution evaluated, upfront capital costs, modest energy efficiency, reliance on critical materials and pre-sulfided catalysts, and greenhouse gas emissions from heating are opportunities for further development.

Abstract Complications are plausible events during surgical operations. Surgical complications profoundly impact surgeons, often called “second victims” of adverse events. These complications trigger a range of emotional and psychological responses, including guilt, anxiety, heightened empathy, and the looming threat of burnout. Moreover, the toll extends to physical health, with chronic stress and sleep disturbances taking their toll. Surgeons’ social lives are not immune to the fallout, and their career satisfaction may wane, pushing some towards defensive medicine practices. While mentorship, counselling, and peer support are crucial support mechanisms, they encounter barriers such as time constraints and the fear of negative perceptions. This paper suggests practical recommendations, including comprehensive wellness programmes, a streamlined badge card system for easy access to resources, and mindfulness training to mitigate stress and burnout. Recognising and proactively addressing these multifaceted impacts is imperative for cultivating a resilient medical community capable of providing optimal patient care.

Objective: This prospective study aimed to evaluate the analgesic effects of acetaminophen and Transcutaneous Electric Nerve Stimulation (TENS) therapy for pain control. Methods: Forty orthodontic patients who underwent fixed orthodontic treatment were randomly assigned to one of 3 groups: (1) acetaminophen, (2) TENS therapy, or (3) control. Pain was evaluated at 12, 24, 36, and 48 hours after the placement of both 0.014" NiTi and 0.016" NiTi archwires using a 10 cm visual analogue scale (VAS). Because the data were found to be non-normal, Kruskal-Wallis test was employed for both stage I and stage II intra-group comparisons. Results: For both stage I and stage II, evaluation of the VAS scores for all 3 groups at different time intervals showed that the difference between groups A and B was statistically insignificant (p>0.05). The scores of Group A compared to Group C were significant, and Group B compared to Group C showed significant values. Conclusion: Both TENS and acetaminophen reduced the pain experienced by patients compared with the placebo group. The acetaminophen group showed VAS results similar to those of the TENS group.

Abdominal tuberculosis, particularly affecting the hepatobiliary system, presents a diagnostic challenge due to its rarity and its tendency to mimic neoplastic conditions. Tuberculosis of the gallbladder, especially in the absence of pulmonary infection, is exceedingly rare. We present a case of isolated tubercular cholecystitis in a 41-year-old female initially suspected to have neoplastic etiology. Radiological imaging revealed thickened gallbladder wall with heterogenous enhancement extending into the subcutaneous plane. Histopathological examination post-cholecystectomy confirmed tubercular etiology with epithelioid cell granulomas and focal necrosis, alongside the presence of acid-fast bacilli. Such cases pose diagnostic dilemmas due to overlapping clinical and radiological features with gallbladder carcinoma. This report emphasizes the importance of considering tuberculosis in differentials, particularly in endemic regions like India, even without pulmonary symptoms. Treatment involves postoperative administration of anti-tubercular drugs, with the preoperative diagnosis being challenging and rarely achieved due to the avoidance of invasive procedures like fine needle aspiration in suspected carcinoma cases. The rarity of isolated gallbladder tuberculosis underscores the necessity for comprehensive diagnostic evaluations and awareness among clinicians in endemic regions.

Hydrogen-based direct reduced iron (H2-DRI) is an alternative pathway for low-carbon steel production. Yet, the lack of established process and business models defining “green steel” makes it difficult to understand what the respective H2 price has to be in order to be competitive with commercial state-of-the-art natural gas DRI. Given the importance of establishing break-even H2 prices and CO2 emission reduction potentials of H2-DRI, this study conducted techno-economic analyses of several design and operation scenarios for DRI systems. Results show that renewable H2 use in integrated DRI steel mills for both heating and the reduction of iron ore can reduce direct CO2 emissions by as much as 85%, but would require an H2 procurement cost of $1.63 per kg H2 or less. When using H2 only for iron ore reduction, economic viability is reached at an H2 procurement cost of $1.70 per kg, while achieving a CO2 emission reduction of 76% at the plant site. System design optimization strategies around excess H2 ratios in the DRI top gas and the H2 recycle pressurization can further improve performance and economics. Low H2 excess ratios are particularly attractive as they reduce pre-heating energy requirements and offer integration opportunities with static recycle ejectors if H2 is supplied at sufficiently high pressure. The potential of utilizing the electric arc furnace off-gas is shown to be much more synergistic with H2-DRI than natural gas-DRI and can increase the break-even H2 procurement cost by up to 7¢ per kg H2. Such findings are critical for setting technical performance criteria for H2 supply and storage in the iron and steel sector.

INTRODUCTION: Hypoxia inducible factor 2-alpha (HIF2α) mediates cellular responses to hypoxia and is over-expressed in glioblastoma (GBM). PT2385 is an oral HIF2α inhibitor with in vivo activity against GBM. METHODS: A two-stage single-arm open-label phase II study of adults with GBM at first recurrence following chemoradiation with measurable disease was conducted through the Adult Brain Tumor Consortium. PT2385 was administered at the phase II dose (800 mg b.i.d.). The primary outcome was objective radiographic response (ORR = complete response + partial response, CR + PR); secondary outcomes were safety, overall survival (OS), and progression free survival (PFS). Exploratory objectives included pharmacokinetics (day 15 Cmin), pharmacodynamics (erythropoietin, vascular endothelial growth factor), and pH-weighted amine- chemical exchange saturation transfer (CEST) MRI to quantify tumor acidity at baseline and explore associations with drug response. Stage 1 enrolled 24 patients with early stoppage for ≤ 1 ORR. RESULTS: Of the 24 enrolled patients, median age was 62.1 (38.7-76.7) years, median KPS 80, MGMT promoter was methylated in 46% of tumors. PT2385 was well tolerated. Grade ≥ 3 drug-related adverse events were hypoxia (n = 2), hyponatremia (2), lymphopenia (1), anemia (1), and hyperglycemia (1). No objective radiographic responses were observed; median PFS was 1.8 months (95% CI 1.6-2.5) and OS was 7.7 months (95% CI 4.9-12.6). Drug exposure varied widely and did not differ by corticosteroid use (p = 0.12), antiepileptics (p = 0.09), or sex (p = 0.37). Patients with high systemic exposure had significantly longer PFS (6.7 vs 1.8 months, p = 0.009). Baseline acidity by pH-weighted CEST MRI correlated significantly with treatment duration (R2 = 0.49, p = 0.017). Non-enhancing infiltrative disease with high acidity gave rise to recurrence. CONCLUSIONS: PT2385 monotherapy had limited activity in first recurrent GBM. Drug exposure was variable. Signals of activity were observed in GBM patients with high systemic exposure and acidic lesions on CEST imaging. A second-generation HIF2α inhibitor is being studied.

Background: Dolutegravir (DTG)-based antiretroviral therapy (ART) rarely leads to virological failure (VF) and drug resistance in integrase strand transfer inhibitor (INSTI)-naïve persons living with HIV (PLWH). As a result, limited data are available on INSTI-associated drug resistance mutations (DRMs) selected by DTG-containing ART regimens. Methods: We reviewed studies published through July 2023 to identify those reporting emergent major INSTI-associated DRMs in INSTI-naïve PLWH receiving DTG and those containing in vitro DTG susceptibility results using a standardized assay. Results: We identified 36 publications reporting 99 PLWH in whom major nonpolymorphic INSTI-associated DRMs developed on a DTG-containing regimen and 21 publications containing 269 in vitro DTG susceptibility results. DTG-selected DRMs clustered into four largely non-overlapping mutational pathways characterized by mutations at four signature positions: R263K, G118R, N155H, and Q148H/R/K. Eighty-two (82.8%) viruses contained just one signature DRM, including R263K (n = 40), G118R (n = 24), N155H (n = 9), and Q148H/R/K (n = 9). Nine (9.1%) contained ≥1 signature DRM, and eight (8.1%) contained just other DRMs. R263K and G118R were negatively associated with one another and with N155H and Q148H/K/R. R263K alone conferred a median 2.0-fold (IQR: 1.8-2.2) reduction in DTG susceptibility. G118R alone conferred a median 18.8-fold (IQR:14.2-23.4) reduction in DTG susceptibility. N155H alone conferred a median 1.4-fold (IQR: 1.2-1.6) reduction in DTG susceptibility. Q148H/R/K alone conferred a median 0.8-fold (IQR: 0.7-1.1) reduction in DTG susceptibility. Considerably higher levels of reduced susceptibility often occurred when signature DRMs occurred with additional INSTI-associated DRMs. Conclusions: Among INSTI-naïve PLWH with VF and treatment emergent INSTI-associated DRMs, most developed one of four signature DRMs, most commonly R263K or G118R. G118R was associated with a much greater reduction in DTG susceptibility than R263K.