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We demonstrate that a neural network pretrained on text and fine-tuned on code solves mathematics course problems, explains solutions, and generates questions at a human level. We automatically synthesize programs using few-shot learning and OpenAI’s Codex transformer and execute them to solve course problems at 81% automatic accuracy. We curate a dataset of questions from Massachusetts Institute of Technology (MIT)’s largest mathematics courses (Single Variable and Multivariable Calculus, Differential Equations, Introduction to Probability and Statistics, Linear Algebra, and Mathematics for Computer Science) and Columbia University’s Computational Linear Algebra. We solve questions from a MATH dataset (on Prealgebra, Algebra, Counting and Probability, Intermediate Algebra, Number Theory, and Precalculus), the latest benchmark of advanced mathematics problems designed to assess mathematical reasoning. We randomly sample questions and generate solutions with multiple modalities, including numbers, equations, and plots. The latest GPT-3 language model pretrained on text automatically solves only 18.8% of these university questions using zero-shot learning and 30.8% using few-shot learning and the most recent chain of thought prompting. In contrast, program synthesis with few-shot learning using Codex fine-tuned on code generates programs that automatically solve 81% of these questions. Our approach improves the previous state-of-the-art automatic solution accuracy on the benchmark topics from 8.8 to 81.1%. We perform a survey to evaluate the quality and difficulty of generated questions. This work automatically solves university-level mathematics course questions at a human level and explains and generates university-level mathematics course questions at scale, a milestone for higher education.

The escape of bladder cancer from immunosurveillance causes monotherapy to exhibit poor efficacy; therefore, designing a multifunctional nanoparticle that boosts programmed cell death and immunoactivation has potential as a treatment strategy. Herein, we developed a facile one-pot coprecipitation reaction to fabricate cluster-structured nanoparticles (CNPs) assembled from Fe 3 O 4 and iron chlorophyll (Chl/Fe) photosensitizers. This nanoassembled CNP, as a multifunctional theranostic agent, could perform red-NIR fluorescence and change the redox balance by the photoinduction of reactive oxygen species (ROS) and attenuate iron-mediated lipid peroxidation by the induction of a Fenton-like reaction. The intravesical instillation of Fe 3 O 4 @Chl/Fe CNPs modified with 4-carboxyphenylboronic acid (CPBA) may target the BC wall through glycoproteins in the BC cavity, allowing local killing of cancer cells by photodynamic therapy (PDT)-induced singlet oxygen and causing chemodynamic therapy (CDT)-mediated ferroptosis. An interesting possibility is reprogramming of the tumor microenvironment from immunosuppressive to immunostimulatory after PDT-CDT treatment, which was demonstrated by the reduction of PD-L1 (lower “off” signal to the effector immune cells), IDO-1, TGF-β, and M2-like macrophages and the induction of CD8 +  T cells on BC sections. Moreover, the intravesical instillation of Fe 3 O 4 @Chl/Fe CNPs may enhance the large-area distribution on the BC wall, improving antitumor efficacy and increasing survival rates from 0 to 91.7%. Our theranostic CNPs not only demonstrated combined PDT-CDT-induced cytotoxicity, ROS production, and ferroptosis to facilitate treatment efficacy but also opened up new horizons for eliminating the immunosuppressive effect by simultaneous PDT-CDT.

This report describes five patients with treatment-resistant focal segmental glomerulosclerosis and positive B7-1 immunostaining who had a response to abatacept (CTLA-4–Ig), a costimulatory inhibitor that targets B7-1 (CD80). The renal glomeruli are highly specialized structures that ensure selective ultrafiltration of plasma, by which most proteins are retained in the blood. 1 The glomerular filtration barrier consists of the glomerular capillary endothelium, the glomerular basement membrane, and specialized cells, the podocytes, that serve as a final barrier to urinary loss of plasma proteins. 1 Disrupted podocyte function damages the kidney filtration mechanism, resulting in proteinuria and, in some circumstances, the nephrotic syndrome. 1 Proteinuria is common to a heterogeneous group of kidney diseases, including minimal-change disease, FSGS, membranous nephropathy, and diabetic nephropathy, all of which affect millions of persons worldwide and often . . .

The functional activity and differentiation potential of cells are determined by their interactions with surrounding cells. Approaches that allow unbiased characterization of cell states while at the same time providing spatial information are of major value to assess this environmental influence. However, most current techniques are hampered by a tradeoff between spatial resolution and cell profiling depth. Here, we develop a photocage-based technology that allows isolation and in-depth analysis of live cells from regions of interest in complex ex vivo systems, including primary human tissues. The use of a highly sensitive 4-nitrophenyl(benzofuran) cage coupled to a set of nanobodies allows high-resolution photo-uncaging of different cell types in areas of interest. Single-cell RNA-sequencing of spatially defined CD8 + T cells is used to exemplify the feasibility of identifying location-dependent cell states. The technology described here provides a valuable tool for the analysis of spatially defined cells in diverse biological systems, including clinical samples. The development of a photocage-nanobody based technology enabled in-depth analysis of live cells from tissues while retaining their spatial information.

Bidirectional DC–DC converters are key devices in the DC distribution system and the energy storage system (ESS). It is important to consider the safety of the elements in the converter for rapid conversion of the power direction. Damages may occur to the power-related components in the circuit if the direction of the inductor current or the capacitor voltage changes instantaneously. To make the power flow change smoothly and quickly, this research proposed a bidirectional DC–DC converter with rapid energy transition technology implemented in the circuit architecture. The rapid energy bidirectional transition technology added a resonance path based on the LC resonant circuit, allowing rapid energy conversion through the resonance path. Therefore, the energy in the energy storage element could be quickly converted without causing circuit surges. Analyses of the converter operating in the step-up mode, the step-down mode, and the transition operation mode are presented. The proposed circuit architecture had a high voltage-conversion ratio and a simple architecture. A prototype bidirectional DC–DC converter with a full load of 500 W, a low side voltage of 24 V, and a high side voltage of 200 V was developed to prove the concept. The feasibility of the rapid energy bidirectional transition technology was verified by the simulation results and experimental results using the prototype converter. The maximum efficiencies in the step-up mode and the step-down mode were 95.3% and 93.8% respectively. Under full-load conditions, the transient time of the energy transition from the step-up mode to the step-down mode was 17.7 μs, and the transient time of the energy transition from the step-down mode to the step-up mode was 19.3 μs.

The bidirectional DC-DC converters are widely used in the energy storage system (ESS) and DC distribution system. The power capacity is limited when the converter is operated with smooth power transfer. In addition, the directions of the inductor current and the capacitor voltage cannot change instantaneously. In this study, a rapid energy conversion technique for smoothing and accelerating the energy transfer under the same specification of the main components in steady state is proposed. Moreover, a bidirectional DC-DC converter with a high conversion ratio is proposed to overcome the commonly low voltage input from renewable energy sources. The operating principles of the proposed converter’s step-down and step-up modes are discussed in this study. Furthermore, to achieve rapid energy conversion, digital control is a crucial component in the converter system. A digital signal processor is used as the control platform, and a control strategy is formulated to achieve rapid energy conversion. The bidirectional DC-DC prototype converter with a 24 V battery, a DC bus of 200 V, and an output power of 500 W is constructed to confirm the feasibility of rapid energy conversion. The proposed converter can be operated in CCM, BCM, and DCM conditions. The transfer period can be completed within one switching cycle when the proposed converter is operated in BCM or DCM. The energy is freewheeled before energy conversion when the proposed converter is operated in CCM condition. In the experiment, the minimum transfer period is 6.29 µs on the DCM stage.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited treatment options and significant variability in care. Racial and ethnic disparities in ALS management and outcomes have been reported, but findings remain inconsistent. Objectives: This study aimed to evaluate racial and ethnic disparities in ALS care, specifically differences in healthcare utilization, treatment patterns, and survival, within a large healthcare system. Design: This retrospective cohort study analyzed electronic health records from a large healthcare system in Texas for patients diagnosed with ALS between 2013 and 2023, examining racial and ethnic differences in treatment and outcomes. Methods: Patients were identified using International Classification of Diseases (ICD) codes. Baseline characteristics, including race/ethnicity and socioeconomic factors, were collected. Primary outcomes included the use of noninvasive ventilation (NIV), tracheostomy, gastrostomy, mobility aids, and ALS medications; secondary outcomes included time to diagnosis and survival. Racial and ethnic disparities were assessed using generalized linear regression and Cox proportional hazards models, adjusting for demographic and socioeconomic factors. Results: A total of 636 patients were included (74.5% Non-Hispanic White, 5.3% Non-Hispanic Black, 7.4% Hispanic, and 12.7% Other). Non-Hispanic Black patients had significantly higher tracheostomy rates than Non-Hispanic White patients (35.3% vs 8.7%; adjusted odds ratio (OR), 6.20; 95% confidence interval (CI), 2.43–15.84). Hispanic patients had lower odds of receiving riluzole (42.6% vs 61.8%; adjusted OR, 0.36; 95% CI, 0.18–0.71) and higher rates of emergency department visits (adjusted OR, 2.00; 95% CI, 1.09–3.65) and hospitalizations (adjusted OR, 2.57; 95% CI, 1.37–4.81). No significant racial or ethnic differences were observed in time to diagnosis or survival after adjustment. Conclusion: Significant racial and ethnic disparities exist in ALS care, particularly in tracheostomy utilization, medication prescribing, and healthcare access. These findings underscore the need for targeted interventions to promote equitable ALS management, including provider education and improved healthcare accessibility. Plain language summary Understanding racial and ethnic differences in ALS care and survival using electronic health records Why was the study done? Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with no cure. While treatments can help manage symptoms, access to ALS care and treatment may vary by race and ethnicity. Previous studies have reported racial and ethnic disparities in ALS management, but findings have been inconsistent. Understanding these differences is essential for ensuring equitable healthcare access and improving patient outcomes. What did the researchers do? The research team analyzed electronic health records from a large healthcare system in Texas to examine racial and ethnic differences in ALS care. They studied 636 patients diagnosed with ALS between 2013 and 2023, assessing healthcare utilization, treatment patterns, and survival. Statistical models were used to account for demographic and socioeconomic differences. What did the researchers find? Non-Hispanic Black patients were more likely than Non-Hispanic White patients to undergo tracheostomy (35.3% vs 8.7%). Hispanic patients were less likely to receive riluzole, a medication that may slow ALS progression (42.6% vs 61.8%). Hispanic patients also had more emergency room visits and hospitalizations. However, there were no significant racial or ethnic differences in time to ALS diagnosis or overall survival after adjusting for socioeconomic factors. What do the findings mean? The study highlights disparities in ALS care, particularly in access to key treatments and healthcare services. Addressing these gaps requires targeted efforts, such as improving healthcare access, reducing barriers to receiving medications, and educating providers on disparities to ensure equitable ALS care for all patients.

Human papillomavirus (HPV) is an important risk factor for oropharyngeal squamous cell carcinoma (OPSCC). HPV-positive (HPV+) cases are associated with a different pathophysiology, microstructure, and prognosis compared to HPV-negative (HPV−) cases. This review aimed to investigate the potential of magnetic resonance imaging (MRI) to discriminate between HPV+ and HPV− tumours and predict HPV status in OPSCC patients. A systematic literature search was performed on 15 December 2022 on EMBASE, MEDLINE ALL, Web of Science, and Cochrane according to PRISMA guidelines. Twenty-eight studies (n = 2634 patients) were included. Five, nineteen, and seven studies investigated structural MRI (e.g., T1, T2-weighted), diffusion-weighted MRI, and other sequences, respectively. Three out of four studies found that HPV+ tumours were significantly smaller in size, and their lymph node metastases were more cystic in structure than HPV− ones. Eleven out of thirteen studies found that the mean apparent diffusion coefficient was significantly higher in HPV− than HPV+ primary tumours. Other sequences need further investigation. Fourteen studies used MRI to predict HPV status using clinical, radiological, and radiomics features. The reported areas under the curve (AUC) values ranged between 0.697 and 0.944. MRI can potentially be used to find differences between HPV+ and HPV− OPSCC patients and predict HPV status with reasonable accuracy. Larger studies with external model validation using independent datasets are needed before clinical implementation.

To investigate if recurrent autoimmunity explained hyperglycemia and C-peptide loss in three immunosuppressed simultaneous pancreas-kidney (SPK) transplant recipients. We monitored autoantibodies and autoreactive T-cells (using tetramers) and performed biopsy. The function of autoreactive T-cells was studied with in vitro and in vivo assays. Autoantibodies were present pretransplant and persisted on follow-up in one patient. They appeared years after transplantation but before the development of hyperglycemia in the remaining patients. Pancreas transplant biopsies were taken within approximately 1 year from hyperglycemia recurrence and revealed beta-cell loss and insulitis. We studied autoreactive T-cells from the time of biopsy and repeatedly demonstrated their presence on further follow-up, together with autoantibodies. Treatment with T-cell-directed therapies (thymoglobulin and daclizumab, all patients), alone or with the addition of B-cell-directed therapy (rituximab, two patients), nonspecifically depleted T-cells and was associated with C-peptide secretion for >1 year. Autoreactive T-cells with the same autoantigen specificity and conserved T-cell receptor later reappeared with further C-peptide loss over the next 2 years. Purified autoreactive CD4 T-cells from two patients were cotransplanted with HLA-mismatched human islets into immunodeficient mice. Grafts showed beta-cell loss in mice receiving autoreactive T-cells but not control T-cells. We demonstrate the cardinal features of recurrent autoimmunity in three such patients, including the reappearance of CD4 T-cells capable of mediating beta-cell destruction. Markers of autoimmunity can help diagnose this underappreciated cause of graft loss. Immune monitoring during therapy showed that autoimmunity was not resolved by the immunosuppressive agents used.

Purpose The purpose of this study is to investigate how two types of drivers, namely, executive compensation and market competition, can affect hospital quality in the USA. Recently, patients, insurers and regulators have increasingly focused on hospital quality. Understanding the interplay of incentives in this industry is important because in 2019, hospital treatment contributed $1.161bn to health-care costs in the USA. This study answers the call for more studies in the so-called “mixed” industry, where ownership differences can affect organizational objectives and operating constraints. Design/methodology/approach This study explores the roles of hospital executive compensation and industry competition as determinants of health-care quality. Specifically, the study probes the heterogeneity in the factors that influence quality across hospital types in the USA. Findings Using California hospital data from 2006 through 2020, the findings show that the effects of compensation and competition on hospital quality differ by ownership type. Executive compensation is positively associated with quality in for-profit hospitals but is not associated with that of nonprofit hospitals, suggesting for-profit hospitals are more likely to use higher levels of compensation to attract managers with higher ability, whereas the utility function for nonprofit managers may be multidimensional. Within the nonprofit hospital group, competition is more positively associated with quality for religious nonprofits relative to secular nonprofits, suggesting that competition provides more monitoring for religious hospitals. Originality/value Taken together, the findings provide evidence that the drivers of quality vary across hospitals in ways consistent with differences in constraints and objectives across ownership types. The findings are important for regulators seeking to incentivize higher quality. For example, Medicare in the USA has incorporated quality measures into its new hospital reimbursement scheme (value-based purchasing) to incentivize quality. This study proposes that regulators should consider differences across ownership types when evaluating the best ways to incentivize hospital quality.