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Rationale: Airway remodeling in asthma comprises increased airway smooth muscle (ASM), an alteration linked to airway hyperresponsiveness and disease severity. Experimental studies showed that T cells adhere to ASM through vascular cell adhesion molecule-1 (VCAM-1) and drive ASM growth through direct contact between the T cells and smooth muscle alpha-actin (alpha-SMA)(+) cells. Objectives: To support the hypothesis of a T-cell/alpha-SMA(+) cell contact mechanism of ASM remodeling in asthma, using bronchial biopsies. Methods: We performed quantitative morphology on T cells, proliferating cell nuclear antigen (PCNA), alpha-SMA, and VCAM-1 on biopsies from subjects with moderate and severe asthma and healthy control subjects. Measurements and Main Results: We demonstrate ASM cell proliferation and infiltration by T cells in proportion to severity in the subjects with asthma. T cells localized with alpha-SMA(+)PCNA(+) cells, suggesting direct intercellular contact and a relationship with alpha-SMA(+) cell proliferation. Furthermore, the subjects with asthma developed a proliferating compartment of subepithelial alpha-SMA(+), nonorganized airway contractile elements (NOACE), suggesting a phenotype gradient from undifferentiated cells to smooth muscle-like cells. T-cell juxtaposition events were also observed in this compartment and correlated to its mass. The subjects with asthma showed VCAM-1 expression in postcapillary venules and clusters of VCAM-1 immunoreactivity in ASM and NOACE, consistent with a role of VCAM-1 in T-cell/alpha-SMA(+) cell interaction. Conclusions: T cells may induce alpha-SMA(+) cell proliferation through direct intercellular contact. NOACE may in part contribute to ASM growth through differentiation and translocation of alpha-SMA(+) cells. The findings support the role of the T cell in ASM remodeling in asthma. [ABSTRACT FROM AUTHOR]

Background: Many cystic fibrosis (CF) patients display airway hyperresponsiveness and have symptoms of asthma such as cough, wheezing and reversible airway obstruction. Chronic airway bacterial colonization, associated with neutrophilic inflammation and high levels of interleukin-8 (IL-8) is also a common occurrence in these patients. The aim of this work was to determine the responsiveness of airway smooth muscle to IL-8 in CF patients compared to non-CF individuals.Methods: Experiments were conducted on cultured ASM cells harvested from subjects with and without CF (control subjects). Cells from the 2nd to 5th passage were studied. Expression of the IL-8 receptors CXCR1 and CXCR2 was assessed by flow cytometry. The cell response to IL-8 was determined by measuring intracellular calcium concentration ([Ca2+](i)), cell contraction, migration and proliferation.Results: The IL-8 receptors CXCR1 and CXCR2 were expressed in both non-CF and CF ASM cells to a comparable extent. IL-8 (100 nM) induced a peak Ca2+ release that was higher in control than in CF cells: 228 +/- 7 versus 198 +/- 10 nM (p < 0.05). IL-8 induced contraction was greater in CF cells compared to control. Furthermore, IL-8 exposure resulted in greater phosphorylation of myosin light chain (MLC20) in CF than in control cells. In addition, MLC20 expression was also increased in CF cells. Exposure to IL-8 induced migration and proliferation of both groups of ASM cells but was not different between CF and non-CF cells.Conclusion: ASM cells of CF patients are more contractile to IL-8 than non-CF ASM cells. This enhanced contractility may be due to an increase in the amount of contractile protein MLC20. Higher expression of MLC20 by CF cells could contribute to airway hyperresponsiveness to IL-8 in CF patients. [ABSTRACT FROM AUTHOR]

This article proposes a method to improve the efficiency of solar power plants by estimating and forecasting the spatial distribution of direct normal irradiance (DNI) using a sensor network and anemometer data. For this purpose, the proposed approach employs spatio-temporal kriging with an anisotropic spatio-temporal variogram that depends on wind speed to accurately estimate the distribution of DNI in real-time, making it useful for short-term forecast and nowcast of DNI. Finally, the method is validated using synthetic data from varying sky conditions, outperforming another state-of-the-art technique., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eduardo Fernandez Camacho reports was provided by 10.13039/501100000781European Research Council (grant agreement No 789051). Jose Maria Maestre Torreblanca reports financial support was provided by Spain Ministry of Science and Innovation (Grant no. PID2023-152876OB-I00). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Purpose: To determine the degree of renal function deterioration after renal cryoablation in patients with a solitary functioning kidney on the basis of ablation volume., Materials and Methods: Over a 15-year period, 81 percutaneous cryoablations were performed in solitary functioning kidneys. After exclusion of patients with baseline end-stage renal disease (ESRD) and insufficient follow-up, analysis was performed on 65 procedures in 52 patients (40 men; mean age, 63.5 years). The postcryoablation renal function was based on the lowest serum creatinine within 6 months after procedure. Renal function change was defined as percentage glomerular filtration rate (GFR) change. Volumetric analysis was performed on the target lesion, renal parenchyma, and ablation zone., Results: The median tumor diameter was 2.0 cm (range, 0.8-4.7 cm). The median baseline GFR decreased from 56.4 mL/min/1.73 m 2 (range, 17.5-89.7 mL/min/1.73 m 2 ) to 46.9 mL/min/1.73 m 2 (range, 16.5-89.7 mL/min/1.73 m 2 ) at median of 95 days (P < .001), equating to a -7.9% median renal function change (range, -45.0% to +30.7%). All patients had Stage 2 or worse chronic kidney disease, and baseline function did not correlate with renal function change. The median volume of ablated parenchyma was 19.7 mL (range, 2.4-87.3 mL), equating to 8.1% (range, 0.7%-37.2%) of total parenchyma. The volume of parenchymal volume ablated correlated significantly with renal function loss, whereas age, hypertension, and diabetes mellitus did not. No patient developed ESRD within 1 year after cryoablation., Conclusions: Cryoablation in solitary functioning kidneys resulted in a modest reduction in renal function, even in patients with chronic kidney disease and ablations of up to 20% of renal parenchymal volume., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Pregnancy is associated with profound changes in immunity. However, pregnancy-related respiratory immune adaptations in response to influenza infection and their impact on disease severity remain unclear. Here, we describe, in a preclinical model of mid-gestation pregnancy, a mechanism of enhanced host defense against influenza A virus (IAV) localized to the nasal cavity that limits viral replication and reduces the magnitude of intrapulmonary immune responses. Consequently, the pregnant mice show reduced pulmonary pathology and preserved airway function after IAV infection. The early restriction of viral replication is independent of type I interferon (IFN) but dependent on increased antimicrobial peptides (AMPs) driven by interleukin-17 + (IL-17 + ) γδ + T cells within the nasal passages. This pathway of host defense against IAV infection in the upper airways during pregnancy restricts early viral infection and prevents virus dissemination into the lung supporting maternal fitness.

Introduction: The use of strategic learning strategies has been positively associated with academic performance in several graduate health profession programs. This finding suggests that it may be an important construct to explore in Doctor of Physical Therapy (DPT) education. The Learning and Study Strategies Inventory (LASSI) summarizes a student's perception and use of 10 learning and study strategies., Review of Literature: Although the LASSI has limited reporting in DPT education, other health care education programs have shown correlation with academic performance. The purpose of this study was to examine DPT students' early perceptions of strategic learning with descriptive summaries of LASSI data and examine correlations between demographic and admissions-related data., Subjects: Matriculated DPT students (n = 294) at a 2-year hybrid program who completed the LASSI at orientation in 2020 and 2021., Methods: This was a descriptive study that retrospectively analyzed LASSI scores in entry-level DPT students. LASSI score differences among demographic groups and Spearman's rho correlations between the LASSI, Graduate Record Examination (GRE) scores, grade point averages, grit, and emotional intelligence (EI) were explored., Results: LASSI score means were in the 50th-75th percentile (moderate category) suggesting a need for further development in strategic learning. Group differences in LASSI scores were noted for gender identity (male higher Anxiety management, P < .001; female higher Attitude, P < .001, Time Management, P = .003, and Use of Academic Resources, P = .003), racial-ethnic minoritized group (higher Self-regulation, P = .013), first-generation college students (higher Attitude, P = .047), physical therapy assistants (higher Information Processing, P = .047), students with a primary language other than English (higher Time Management, P = .046), and older students (higher Anxiety management, P = .026). Weak but significant correlations were identified between LASSI scale and component scores and several admissions variables. Highest correlations were with grit (Will, ρ = 0.319, P < .001; Concentration, ρ = 0.312, P < .001), EI (Will, ρ = 0.328, P < .001; Attitude, ρ = 0.302, P < .001; Self-regulation, ρ = 0.382, P < .001; Use of Academic Resources ρ = 0.331, P < .001), and quantitative GRE scores (Anxiety management, ρ = 0.341, P < .001)., Discussion/conclusion: All LASSI scale scores and components were in the moderate category, potentially indicating a need to coach and develop strategic learning strategies. Group differences in LASSI scores may represent varied student needs. The weak relationship between LASSI scores and admissions variables could suggest that the constructs measured by LASSI are not currently captured through typical DPT admissions practices., Competing Interests: The author declares no conflicts of interest., (Copyright © 2024 Academy of Physical Therapy Education, APTA.)

Classic Hodgkin lymphoma (cHL) is highly curable at all stages. Research efforts over the past few decades have largely focused on interim PET-adapted strategies for therapy de-escalation or intensification. The overarching goals have been to increase cure rates, minimize potential therapy-related effects, and optimize survivorship. Better understanding of the biology of cHL has led to the development and approval of effective novel agents including the antibody-drug conjugate brentuximab vedotin and the checkpoint inhibitor immunotherapies. In this review, we discuss recent trial results and how these agents are integrated into clinical practice with the goal of further optimizing outcomes.

Cross talk between T cells and airway smooth muscle (ASM) may play a role in modulating asthmatic airway inflammation and remodeling. Infiltrating T cells have been observed within the ASM bundles of asthmatics, and a wide range of direct and indirect interactions between T cells and ASM has been demonstrated using various in vitro and in vivo model systems. Contact-dependent mechanisms such as ligation and activation of cellular adhesion and costimulatory molecules, as well as the formation of lymphocyte-derived membrane conduits, facilitate the adhesion, bidirectional communication, and transfer of materials between T and ASM cells. T cell-derived cytokines, particularly of the Th1, Th2, and Th17 subsets, modulate the secretome, proliferation, and contractility of ASM cells. This review summarizes the mechanisms governing T cell-ASM cross talk in the context of asthma. Understanding the underlying mechanistic basis is important for directing future research and developing therapeutic interventions targeted toward this complex interaction.

Objective: To compare the effectiveness of inhaled Magnesium Sulfate associated with Salbutamol versus Inhaled Salbutamol alone in patients with moderate and severe asthma exacerbations., Method: Clinical, prospective and randomized study with patients between 3 and 14 years of age divided into two groups: one to receive inhaled salbutamol associated with magnesium sulfate (GSM), the other to receive inhaled salbutamol alone (GS). The sample consisted of 40 patients, 20 patients in each group. Severity was classified using the modified Wood-Downes score, with values between 4 and 7 classified as moderate and 8 or more classified as severe., Results: Post-inhalation scores decreased both in patients who received salbutamol and magnesium and in those who received salbutamol alone, with no statistically significant difference between the groups., Conclusions: Despite the benefits when administered intravenously, inhalation of the drug alone or in combination did not reduce the severity of the exacerbation., Competing Interests: Conflicts of interest The authors declare no conflicts of interest, and they each contributed fully to the preparation of this manuscript., (Copyright © 2024 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

The optimal treatment of classic Hodgkin Lymphoma (cHL) requires an individualized approach, with therapy guided by pretreatment clinical risk stratification and interim response assessment with positron emission tomography (PET). The overall goal is to achieve high cure rates while minimizing acute toxicity and late therapy-related effects. Interim PET-adapted strategies (iPET) were initially developed with traditional chemotherapy, reducing intensity after interim complete response and escalating treatment for patients with iPET+ disease. Recently, novel agents including brentuximab vedotin and the checkpoint inhibitor immunotherapies (CPIs) pembrolizumab and nivolumab have been adopted into the front-line treatment of cHL, and PET-adapted approaches may be relevant for these drugs as well. In this review we discuss response-adapted strategies utilizing novel agents, consider challenges including indeterminate radiographic findings with CPIs, and address emerging techniques for response assessment including new PET-based imaging metrics and the role of circulating tumor DNA., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.S.M. reports no potential conflicts of interest. R.H.A. reports research funding from Genentech/Roche, Gilead, Merck, Millennium, Pharmacyclics, Regeneron, BeiGene, and Seagen Inc; and has served as a consultant for Autolus, Genentech/Roche, Gilead, and ADCT., (Copyright © 2024 Elsevier Inc. All rights reserved.)

RATIONALE AND OBJECTIVES: Near-peer paradigms have been demonstrated effective in supporting how students navigate novel clinical environments. In this study, we describe an innovative model of incorporating teaching assistants (TAs) into a core radiology clerkship and investigate both its perceived educational value by clinical-year learners and its perceived impact on professional growth by TAs. MATERIALS AND METHODS: At one U.S. medical school, the core clinical year includes a clerkship in radiology incorporating both reading room exposure and a didactic curriculum. Radiology faculty deliver a variety of traditional and interactive, "dynamic" lectures, while medical student TAs deliver additional dynamic sessions, including a final TA-created review session. The educational value of each didactic session by clerkship students was assessed using a five-point scale survey, and the professional value of the experience by TAs was assessed using a five-point Likert survey. RESULTS: Spanning from 2020 to 2023, 268 (74.4%) clinical-year students submitted the post-clerkship survey, with the didactic review sessions created and led by TAs receiving the highest ratings of any didactic session. Of 16 former TAs, 12 (75%) completed the post-service survey, with all respondents agreeing or strongly agreeing that they enjoyed and would recommend their experience, and that it enhanced their interest in radiology and in academic medicine. CONCLUSION: Near-peer education in a core radiology clerkship enhances the experience of the learner through peer guidance and the experience of the teacher through professional development. These findings may increase student interest in pursuing academic radiology as a career and invite opportunities for broadening medical school education in radiology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

The transcription factors (TFs) MyoCD (myocardin) and Elk-1 (ETS Like-1 protein) competitively bind to SRF (serum response factor) and control myogenic- and mitogenic-related gene expression in smooth muscle, respectively. Their functions are therefore mutually inhibitory, which results in a contractile-versus-proliferative phenotype dichotomy. Airway smooth muscle cell (ASMC) phenotype alterations occur in various inflammatory airway diseases, promoting pathological remodeling and contributing to airflow obstruction. We characterized MyoCD and Elk-1 interactions and their roles in phenotype determination in human ASMCs. MyoCD overexpression in ASMCs increased smooth muscle gene expression, force generation, and partially restored the loss of smooth muscle protein associated with prolonged culturing while inhibiting Elk-1 transcriptional activities and proliferation induced by EGF (epidermal growth factor). However, MyoCD overexpression failed to suppress these responses induced by FBS, as FBS also upregulated SRF expression to a degree that allowed unopposed function of both TFs. Inhibition of the RhoA pathway reversed said SRF changes, allowing inhibition of Elk-1 by MyoCD overexpression and suppressing FBS-mediated contractile protein gene upregulation. Our study confirmed that MyoCD in increased abundance can competitively inhibit Elk-1 function. However, SRF upregulation permits a dual contractile-proliferative ASMC phenotype that is anticipated to exacerbate pathological alterations, whereas therapies targeting SRF may inhibit pathological ASMC proliferation and contractile protein gene expression.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of haematological cancers with generally poor clinical outcomes. However, a subset of patients experience durable disease control, and little is known regarding long-term outcomes. The International T-cell Lymphoma Project (ITCLP) is the largest prospectively collected cohort of patients with PTCLs, providing insight into clinical outcomes at academic medical centres globally. We performed a long-term outcome analysis on patients from the ITCLP with available 10-year follow-up data (n = 735). The overall response rate to first-line therapy was 68%, while 5- and 10-year overall survival estimates were 49% and 40% respectively. Most deaths occurred prior to 5 years, and for patients alive at 5 years, the chance of surviving to 10 years was 84%. However, lymphoma remained the leading cause of death in the 5- to 10-year period (67%). Low-risk International Prognostic Index and Prognostic Index for T-cell lymphoma scores both identified patients with improved survival, while in multivariate analysis, age >60 years and Eastern Cooperative Oncology Group performance status 2-4 were associated with inferior outcomes. The favourable survival seen in patients achieving durable initial disease control emphasizes the unmet need for optimal front-line therapeutic approaches in PTCLs., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background: During COVID-19, hospitality businesses (e.g. bars, restaurants) were closed/restricted whilst off-sales of alcohol increased, with health consequences. Post-covid, governments face lobbying to support such businesses, but many health services remain under pressure. We appraised 'sweetspot' policy options: those with potential to benefit public services and health, whilst avoiding or minimising negative impact on the hospitality sector., Methods: We conducted rapid non-systematic evidence reviews using index papers, citation searches and team knowledge to summarise the literature relating to four possible 'sweetspot' policy areas: pricing interventions (9 systematic reviews (SR); 14 papers/reports); regulation of online sales (1 SR; 1 paper); place-shaping (2 SRs; 18 papers/reports); and violence reduction initiatives (9 SRs; 24 papers/reports); and led two expert workshops (n = 11)., Results: Interventions that raise the price of cheaper shop-bought alcohol appear promising as 'sweetspot' policies; any impact on hospitality is likely small and potentially positive. Restrictions on online sales such as speed or timing of delivery may reduce harm and diversion of consumption from on-trade to home settings. Place-shaping is not well-supported by evidence and experts were sceptical. Reduced late-night trading hours likely reduce violence; evidence of impact on hospitality is scant. Other violence reduction initiatives may modestly reduce harms whilst supporting hospitality, but require resources to deliver multiple measures simultaneously in partnership., Conclusions: Available evidence and expert views point to regulation of pricing and online sales as having greatest potential as 'sweetspot' alcohol policies, reducing alcohol harm whilst minimising negative impact on hospitality businesses., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: N.F. declares that she has received fees for serving as an expert witness for the Government of Ireland in a challenge to pandemic-related restrictions on licensed premises. T.S. declares receipt of fees for serving as an expert witness on behalf of (i) the Ontario Public Service Employees Union in a challenge to 7/11′s applications for liquor licences in their many corner stores and gas stations; (ii) individuals seeking damages for injuries caused by accidents involving intoxicated people. He also declares receiving research funds, travel expenses and personal fees from government alcohol monopolies for research on alcohol and public health policy in Sweden, Finland and Canada. R.O., I.U., J.M., M.C., K.G., K.H., K.H., C.W., E.M., P.M., J.R., Z.Q. and C.A. declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Rationale and Objectives: A novel three-day radiology course, PRIMER, directly preceding medical students' clinical year, was created and assessed. The required course consisted of large group lecture sessions, small group breakout sessions, and individual assignments. Though early exposure to radiology has been described in preclinical anatomy curricula, few schools offer immersive experiences to radiology as a direct predecessor to the wards., Materials and Methods: An identical survey was distributed prior to and at the completion of the PRIMER course. Students' perceptions of radiology were assessed through Likert-style questions. Students' knowledge of radiological concepts was assessed through multiple choice questions (MCQs) related to key concepts, MCQs in which students selected the most likely diagnosis, and hotspot questions in which learners had to select the area of greatest clinical importance. Mean pre- and post-course student perception scores were compared using a T-test. For knowledge-based questions, each student received an exam score, and mean pre- and post-exam scores were compared using a T-test., Results: Students' opinions of radiology changed significantly in a favorable direction across all tested questions between inception and conclusion of PRIMER (p < 0.01). Students demonstrated superior knowledge of radiological concepts after course completion (posttest mean 52% vs pretest mean 26.3%, p < 0.01)., Conclusion: The novel radiology PRIMER course promoted a positive impression of radiology and increased medical students' knowledge of key concepts. These results suggest that a condensed introductory radiology curriculum delivered at a key moment in the overarching curriculum can have a significant impact on medical students' perceptions and knowledge., Competing Interests: Declaration of competing interest The authors declare no relevant conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to evaluate long-term morphologic changes occurring in the liver after TIPS creation with correlation with hepatic function to gain insight on the physiologic impact of TIPS on the liver., Methods: This retrospective study included patients who underwent TIPS creation between 2005 and 2022 and had contrasted CT or MRI studies prior to and between 1 and 2 years post procedure. Strict exclusion criteria were applied to avoid confounding. Parenchymal volume and vessel measurements were assessed on the pre- and post-TIPS CT or MRI and MELD scores calculated., Results: Of 580 patients undergoing TIPS creation, 65 patients (mean age, 55 years; 36 males) had pre-TIPS and post-TIPS imaging meeting inclusion criteria at median 16.5 months. After TIPS, the mean MELD score increased (12.9 to 15.4; p = 0.008) and total liver volume decreased (1730 to 1432 mL; p < 0.001). However, the magnitude of volume change did not correlate with MELD change. Neither portosystemic gradient nor TIPS laterality correlated with total or lobar hepatic volume changes or MELD changes. The main portal vein diameter increased (15.0 to 18.7 mm; p < 0.001). Thrombosis of the hepatic vein used for TIPS creation resulted in a mean increase in MELD of +4.1 compared to -2.1 in patients who had a patent and normal hepatic vein (p = 0.007)., Conclusions: Given lack of correlation between portosystemic gradient, hepatic atrophy, hepatic function, and TIPS laterality, the alterations in portal flow dynamics after TIPS may not be impactful to hepatic function. However, hepatic vein patency after TIPS correlated with improved hepatic function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The discussion and critical appraisal of medical literature in a group setting has been incorporated in health care education for over a century and remains one of the structured didactic activities in Accreditation Council for Graduate Medical Education radiology residency educational requirements. The panel members of the "Radiology Journal Club: Best Practice from Across the Country" Task Force of the Association of University Radiologists Radiology Research Alliance have collated best practices from radiology and other medical specialties to help radiology departments to establish or resume journal club as part of their residency or fellowship educational program. Key components include a leadership team to designate mentors, facilitators, and ad hoc content experts; to establish the scope, goals and learning objectives; to identify the target audience and level of faculty and trainee involvement; and establish appropriate meeting frequency. Providing relevant and easily accessible resources, mentoring and other preparatory materials can build trainee skill in critical appraisal of the medical literature, foster innovation, and advance radiological knowledge in this ever-evolving discipline., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

In asthma, CD4 + T-cell interaction with airway smooth muscle (ASM) may enhance its contractile properties and promote its proliferation. However, less is known about the effects of this interaction on T cells. To explore the consequences of interaction of CD4 + T cells with ASM we placed the cells in co-culture and analyzed the phenotypic and functional changes in the T cells. Effector status as well as cytokine expression was assessed by flow cytometry. An increase in CD45RA - CD45RO + memory T cells was observed after co-culture; however, these cells were not more responsive to CD3/28 restimulation. A reduction in mitochondrial coupling and an increase in the production of mitochondrial reactive oxygen species by CD4 + T cells post-restimulation suggested altered mitochondrial metabolism after co-culture. RNA sequencing analysis of the T cells revealed characteristic downregulation of effector T-cell-associated genes, but a lack of upregulation of memory T-cell-associated genes. The results of this study demonstrate that ASM cells can induce a phenotypic shift in CD4 + T cells into memory-like T cells but with reduced capacity for activation., (© 2024 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH.)

Chemoproteomics has made significant progress in investigating small-molecule-protein interactions. However, the proteome-wide profiling of cysteine ligandability remains challenging to adapt for high-throughput applications, primarily due to a lack of platforms capable of achieving the desired depth using low input in 96- or 384-well plates. Here, we introduce a revamped, plate-based platform which enables routine interrogation of either ∼18,000 or ∼24,000 reactive cysteines based on starting amounts of 10 or 20 μg, respectively. This represents a 5-10X reduction in input and 2-3X improved coverage. We applied the platform to screen 192 electrophiles in the native HEK293T proteome, mapping the ligandability of 38,450 reactive cysteines from 8,274 human proteins. We further applied the platform to characterize new cellular targets of established drugs, uncovering that ARS-1620, a KRAS G12C inhibitor, binds to and inhibits an off-target adenosine kinase ADK. The platform represents a major step forward to high-throughput proteome-wide evaluation of reactive cysteines., Competing Interests: Declaration of interests S.P.G. is on the advisory board for Thermo Fisher Scientific, Cedilla Therapeutics, Casma Therapeutics, Cell Signaling Technology, and Frontier Medicines., (Copyright © 2023 Elsevier Ltd. All rights reserved.)