Foundation Funding Research Articles

Pengelolaan Pembiayaan Pendidikan di Sekolah Menengah Pertama Swasta

This study aims to explore the management of educational financing at SMP Islam Bakti Asih, where efficient financial management is key to achieving educational goals. The research is motivated by the financial challenges faced by private schools due to limited resources, affecting the quality of education and the welfare of teaching staff. Using a qualitative phenomenological approach, data were collected through observations, in-depth interviews, and documentation on budget planning, fund utilization, and financial oversight. The key findings indicate that the primary sources of funding come from the foundation and government (BOS) funds, which are utilized through detailed budget planning and regular financial audits to ensure transparency and accountability. The implications of these findings highlight the importance of comprehensive and proactive financial management, not only to maintain the school's financial stability but also to enhance the quality of education provided. This study contributes to the literature on educational financial management by providing insights into best practices for managing funds in private schools. Additionally, the limitations of this study include its narrow focus on a single school and the limited number of respondents, which opens opportunities for further research in broader contexts.

Immigrant Grassroots Associations in the Netherlands: A Sense-Making Approach to Understanding Exclusion From Endowed Foundation Funding

Immigrant Grassroots Associations in the Netherlands: A Sense-Making Approach to Understanding Exclusion From Endowed Foundation Funding

Sequential [177Lu]Lu-PSMA-617 and docetaxel versus docetaxel in patients with metastatic hormone-sensitive prostate cancer (UpFrontPSMA): a multicentre, open-label, randomised, phase 2 study

Lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 improves survival and quality of life in patients with metastatic castration-resistant prostate cancer, but whether it confers a benefit in hormone-sensitive disease is unknown. We aimed to evaluate [177Lu]Lu-PSMA-617 before docetaxel treatment in patients with de-novo high-volume metastatic hormone-sensitive prostate cancer. UpFrontPSMA was an investigator-initiated, multicentre, open-label, randomised, phase 2 trial done at 11 Australian hospitals. Eligible patients had prostate adenocarcinoma without clinically significant neuroendocrine differentiation or small-cell histology, were aged 18 years or older, had less than 4 weeks on androgen deprivation therapy, had an Eastern Cooperative Oncology Group performance status of 0-2, and had high-volume PSMA-avid disease on [68Ga]Ga-PSMA-11 PET-CT with no major discordance on 2-[18F] fluorodeoxyglucose-PET-CT. Patients were randomly assigned (1:1) to the experimental treatment ([177Lu]Lu-PSMA-617 followed 6 weeks later by docetaxel) or standard-of-care treatment (docetaxel alone) using computer-based block randomisation with random block sizes, stratified by disease volume by conventional imaging and duration of androgen deprivation therapy at the time of registration. Neither patients nor investigators were masked to treatment assignment. Patients in the experimental group received two cycles of [177Lu]Lu-PSMA-617 7·5 GBq every 6 weeks intravenously, followed 6 weeks later by six cycles of docetaxel 75 mg/m2 every 3 weeks intravenously, whereas patients in the standard-of-care treatment group received six cycles of docetaxel 75 mg/m2 every 3 weeks intravenously. All patients received continuous androgen deprivation therapy. The primary endpoint was undetectable prostate-specific antigen (≤0·2 ng/mL) at 48 weeks, assessed using a modified intention-to-treat analysis. The trial is registered with ClinicalTrials.gov, NCT04343885. Between May 5, 2020, and April 18, 2023, 130 patients were randomly assigned, 63 (48%) to [177Lu]Lu-PSMA-617 plus docetaxel and 67 (52%) to docetaxel alone. All patients were male and no race or ethnicity data were collected. Median follow-up was 2·5 years (IQR 1·8-3·0). Four patients in the docetaxel alone group withdrew consent after randomisation and no data beyond screening were collected. An additional four patients were not evaluable for the primary endpoint at 48 weeks (two in each group). 25 (41%) of 61 patients (95% CI 30-54) in the [177Lu]Lu-PSMA-617 plus docetaxel group had undetectable PSA at 48 weeks compared with ten (16%) of 61 patients (9-28) in the docetaxel alone group (OR 3·88, 95% CI 1·61-9·38; p=0·0020). The most common grade 3 or 4 treatment-related adverse events were febrile neutropenia (seven [11%] of 63 patients in the [177Lu]Lu-PSMA-617 plus docetaxel group vs six [10%] of 63 patients in the docetaxel alone group) and diarrhoea (four [6%] of 63 patients vs none). Serious adverse events occurred in 16 (25%) patients in the [177Lu]Lu-PSMA-617 plus docetaxel group (none were definitely related to [177Lu]Lu-PSMA-617) and 16 (25%) patients in the docetaxel alone group. No treatment-related deaths occurred. [177Lu]Lu-PSMA-617 followed by docetaxel improved antitumour activity in patients with de-novo high-volume metastatic hormone-sensitive prostate cancer compared with docetaxel alone, without increased toxic effects. Our data potentially support a role for [177Lu]Lu-PSMA-617 in metastatic hormone-sensitive prostate cancer. Prostate Cancer Research Alliance (Movember Foundation and Australian Government Medical Research Future Fund), US Department of Defence Impact Award-Clinical Trials, Endocyte/Advanced Accelerator Applications (a Novartis company), Australian Nuclear Science and Technology Organization, Victorian Cancer Agency, University of Melbourne, and Peter MacCallum Cancer Foundation.

Qualitative Exploration of the "Guilt Gap" Among Physician-Faculty with Caregiving Responsibilities.

Introduction: Differences in time commitments and resources contribute to the difficulties of work-life integration for many physician-scientists, particularly for women with family caregiving responsibilities. Understanding the challenges faced by this population is critical for the retention of these critical members of the workforce. Methods: We conducted semi-structured telephone interviews with recipients of the 2017 Doris Duke Charitable Foundation's Fund to Retain Clinical Scientists (FRCS) and reviewed application narratives from the 2020 award recipients. Award recipients were asked about their caregiving responsibilities and careers, particularly as they related to the impact of the FRCS award and the aftereffects of the COVID-19 pandemic. Analysts then iteratively revised the coding scheme and interpreted the data using qualitative thematic analysis. Results: Of the 14 interviewees and 19 narrative contributors, 25 (76%) were women. The main qualitative themes that emerged were as follows: (1) women experience unrealistically high caregiving burdens, (2) women are overburdened by disadvantageous and undervalued expectations at work, (3) work-life expectations increased during the COVID-19 pandemic, and (4) unrealistic work-life expectations led to guilt and burnout. Conclusions: These findings provide a rich understanding of the factors contributing to guilt and burnout among physician-scientists, particularly women, and how work duties that increase physician obligations exacerbated these challenges. Understanding these experiences is critical to supporting and retaining a diverse workforce in academic medicine.

A transformer-based deep learning model for early prediction of lymph node metastasis in locally advanced gastric cancer after neoadjuvant chemotherapy using pretreatment CT images

Early prediction of lymph node status after neoadjuvant chemotherapy (NAC) facilitates promptly optimization of treatment strategies. This study aimed to develop and validate a deep learning network (DLN) using baseline computed tomography images to predict lymph node metastasis (LNM) after NAC in patients with locally advanced gastric cancer (LAGC). A total of 1205 LAGC patients were retrospectively recruited from three hospitals between January 2013 and March 2023, constituting a training cohort, an internal validation cohort, and two external validation cohorts. A transformer-based DLN was developed using 3D tumor images to predict LNM after NAC. A clinical model was constructed through multivariate logistic regression analysis as a baseline for subsequent comparisons. The performance of the models was evaluated through discrimination, calibration, and clinical applicability. Furthermore, Kaplan-Meier survival analysis was conducted to assess overall survival (OS) of LAGC patients at two follow-up centers. The DLN outperformed the clinical model and demonstrated a robust performance for predicting LNM in the training and validation cohorts, with areas under the curve (AUCs) of 0.804 (95% confidence interval [CI], 0.752-0.849), 0.748 (95% CI, 0.660-0.830), 0.788 (95% CI, 0.735-0.835), and 0.766 (95% CI, 0.717-0.814), respectively. Decision curve analysis exhibited a high net clinical benefit of the DLN. Moreover, the DLN was significantly associated with the OS of LAGC patients [Center 1: hazard ratio (HR), 1.789, P<0.001; Center 2:HR, 1.776, P=0.013]. The transformer-based DLN provides early and effective prediction of LNM and survival outcomes in LAGC patients receiving NAC, with promise to guide individualized therapy. Future prospective multicenter studies are warranted to further validate our model. National Natural Science Foundation of China (NO. 82373432, 82171923, 82202142), Project Funded by China Postdoctoral Science Foundation (NO. 2022M720857), Regional Innovation and Development Joint Fund of National Natural Science Foundation of China (NO. U22A20345), National Science Fund for Distinguished Young Scholars of China (NO. 81925023), Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application (NO. 2022B1212010011), High-level Hospital Construction Project (NO. DFJHBF202105), Natural Science Foundation of Guangdong Province for Distinguished Young Scholars (NO. 2024B1515020091).

Ohio

Ohio education spending in this biennium represents the largest commitment of state appropriations. Much of this money is distributed through a new foundation funding formula.

Arkansas

This article examines changes in educational funding for fiscal year 2023 in the state of Arkansas in the United States. In 2023 the state was ranked 47th in education attainment, 37th in per- pupil spending for public K-12 schools and had the 5th highest poverty rate in the United States. The state legislature passed a minimum starting teacher salary of $50,000 for the 2023–2024 school year, up from $34,900. The legislation also provided an increase of $2,000 to teachers who were already making $50,000 or more. This increase in teacher salaries is estimated to cost the state $180 million each year. The legislature also increased the foundation funding amount per pupil by $205 and increased most categorical funds by roughly two percent. Arkansas uses a productivity funding model as its method of funding higher education but only increased higher education funding by 1.5%. The Arkansas LEARNS Act created a voucher system whereby any student who is eligible to enroll in a public school can receive funding to attend a private school or be homeschooled. This system will be fully implemented in three years enabling any student to be eligible for funds. The state spends approximately 31% of its budget on P-12 education and 15% on higher education.

Lenalidomide and dexamethasone for Rosai-Dorfman disease: a single arm, single center, prospective phase 2 study

Rosai-Dorfman disease (RDD) is a rare heterogeneous histiocytic disorder lacking standardized first-line treatment. This single-center, phase 2 prospective study enrolled 13 newly diagnosed and 10 recurrent RDD patients from June 2021 to March 2023at Peking Union Medical College Hospital (Beijing, China). Lenalidomide 25mg days 1-21 plus dexamethasone 40mg days 1, 8, 15, 22 was administered in 28-day cycles, totaling 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate (ORR) to lenalidomide and dexamethasone (RD) regimen, toxicity, and overall survival (OS) measured from RD start to death or last follow-up. OS and PFS were estimated according to Kaplan-Meier survival analysis and compared with the log-rank test. For OS and OR rate, 95% confidence limits were obtained using the Clopper-Pearson method, with standard methods used for PFS. p<0.05 was considered statistically significant. The trial was registered with ClinicalTrials.gov (NCT04924647). The median age was 44 years (IQR 35-54). All patients had extranodal RDD. MAPK pathway alterations occurred in 6/18 (33%). Elevated IL-6 and TNF-α were found in 39% (n=9) and 70% (n=16), respectively. All patients received ≥6 cycles (median 12, range 6-12, IQR 10-12). The ORR was 87% (20/23, 95% CI 66%-97%), 30% (n=7) complete remission, 57% (n=13) partial remission). Treatment with RD significantly decreased median serum levels of both IL-6 (from 5.9 (IQR 4.2-8.7) to 2.9 (IQR 2.1-5.9) pg/mL, p=0.031) and TNF-α (from 12.2 (IQR 8.6-17.9) to 8.3 (IQR 6.1-10.5) pg/mL, p=0.0012). With a median 26 months follow-up (range 6-28, IQR 16-28), 4 patients relapsed and none died. Two-year OS and PFS were 100.0% (95% CI 85%-100%) and 69.0% (95% CI 51%-94%), respectively. No grade 3-4 adverse events or discontinuations due to adverse events occurred. Twelve patients (n=12, 52%) had grade 1-2 hematological toxicity. Other toxicities included constipation (n=2, 9%), glucose intolerance (n=2, 9%), edema (n=2, 9%), insomnia (n=1, 4%), and tremor (n=1, 4%). Lenalidomide and dexamethasone regimen is an effective and safe regimen for newly diagnosed and recurrent RDD. National Natural Science Foundation of China, Beijing Natural Science Haidian frontier Foundation Funding, and the National High Level Hospital Clinical Research Funding.

Survival among people with HIV and their families in Denmark 1995–2021: a nationwide population-based cohort study

Survival among people with HIV (PWH) has vastly improved globally over the last few decades but remains lower than among the general population. We aimed to estimate time trends of survival among PWH and their families from 1995 to2021. We conducted a registry-based, nationwide, population-based, matched cohort study. We included all Danish-born PWH from 1995 to 2021 who had been on antiretroviral therapy for 90 days, did not report intravenous drug use, and were not co-infected with hepatitis C (n=4168). We matched population controls from the general population 10:1 to PWH by date of birth and sex (n=41,680). For family cohorts, we identified siblings, mothers, and fathers of PWH and population controls. From Kaplan-Meier tables with age as time scale, we estimated survival from age 25. We compared PWH with population controls and families of PWH with families of population controls to calculate mortality rate ratios adjusted for sex, age, comorbidities, and education (aMRR). The median age of death among PWH increased from 27.5 years in 1995-1997 to 73.9 years (2010-2014), but thereafter survival increased only marginally. From 2015 to 2021, mortality was increased among PWH (aMRR 1.87 (95% CI: 1.65-2.11)) and siblings (aMRR: 1.25 (95% CI: 1.07-1.47)), mothers (aMRR: 1.30 (95% CI: 1.17-1.43)), and fathers (aMRR: 1.15 (95% CI: 1.03-1.29)) of PWH compared to their respective control cohorts. Mortality among siblings of PWH who reported heterosexual route of HIV transmission (aMRR: 1.51 (95% CI: 1.16-1.96)) was higher than for siblings of PWH who reported men who have sex with men as route of HIV transmission (aMRR 1.19 (95% CI: 0.98-1.46)). Survival among PWH improved substantially until 2010, after which it increased only marginally. This may partly be due to social and behavioural factors as PWH families also had higher mortality. Preben and Anna Simonsen's Foundation and Independent Research Fund Denmark.

Study shows few grantmakers funding endowments, despite their advantages

New research shows that fewer than a third of grantmaking foundations fund nonprofit endowments, despite the fact that endowments can be a “powerful grantmaking tool that not only can address longstanding racial inequities but also represents a direct transfer of power,” according to the Bridgespan Group and the Center for Effective Philanthropy.

P24. Plastic Surgery Foundation (PSF) Funding Trends and Publication Metrics for PSF Grant Awardees: A Retrospective 10-year Analysis on Successful Applicants

P24. Plastic Surgery Foundation (PSF) Funding Trends and Publication Metrics for PSF Grant Awardees: A Retrospective 10-year Analysis on Successful Applicants

Federal and foundational research funding trends for cerebrovascular neurosurgeons: the decline of the cerebrovascular surgeon-scientist?

The number of cerebrovascular (CV) surgeons has grown with the rise of endovascular neurosurgery. However, it is unclear whether the number of CV surgeon-scientists has concomitantly increased. With increasing numbers of CV neurosurgeons in the US workforce, the authors analyzed associated changes in National Institutes of Health (NIH) and Neurosurgery Research and Education Foundation (NREF) funding trends for CV surgeons over time. Publicly available data were collected on currently practicing academic CV surgeons in the US. Inflation-adjusted NIH funding between 2009 and 2021 was surveyed using NIH RePORTER and Blue Ridge Institute for Medical Research data. The K12 Neurosurgeon Research Career Development Program and NREF grant data were queried for CV-focused grants. Pearson R correlation, chi-square analysis, and the Mann-Whitney U-test were used for statistical analysis. From 2009 to 2021, NIH funding increased: in total (p = 0.0318), to neurosurgeons (p < 0.0001), to CV research projects (p < 0.0001), and to CV surgeons (p = 0.0018). During this time period, there has been an increase in the total number of CV surgeons (p < 0.0001), the number of NIH-funded CV surgeons (p = 0.0034), and the percentage of CV surgeons with NIH funding (p = 0.370). Additionally, active NIH grant dollars per CV surgeon (p = 0.0398) and the number of NIH grants per CV surgeon (p = 0.4257) have increased. Nevertheless, CV surgeons have been awarded a decreasing proportion of the overall pool of neurosurgeon-awarded NIH grants during this time period (p = 0.3095). In addition, there has been a significant decrease in the number of K08, K12, and K23 career development awards granted to CV surgeons during this time period (p = 0.0024). There was also a significant decline in the proportion of K12 (p = 0.0044) and downtrend in early-career NREF (p = 0.8978) grant applications and grants awarded during this time period. Finally, NIH-funded CV surgeons were more likely to have completed residency less recently (p = 0.001) and less likely to have completed an endovascular fellowship (p = 0.044) as compared with non-NIH-funded CV surgeons. The number of CV surgeons is increasing over time. While there has been a concomitant increase in the number of NIH-funded CV surgeons and the number of NIH grants awarded per CV surgeon in the past 12 years, there has also been a significant decrease in CV surgeons with K08, K12, and K23 career development awards and a downtrend in CV-focused K12 and early-career NREF applications and awarded grants. The latter findings suggest that the pipeline for future NIH-funded CV surgeons may be in decline.

Effects of 3 months of 10-h per-day time-restricted eating and 3 months of follow-up on bodyweight and cardiometabolic health in Danish individuals at high risk of type 2 diabetes: the RESET single-centre, parallel, superiority, open-label, randomised controlled trial

Time-restricted eating (TRE) has been suggested to be a simple, feasible, and effective dietary strategy for individuals with overweight or obesity. We aimed to investigate the effects of 3 months of 10-h per-day TRE and 3 months of follow-up on bodyweight and cardiometabolic risk factors in individuals at high risk of type 2 diabetes. This was a single-centre, parallel, superiority, open-label randomised controlled clinical trial conducted at Steno Diabetes Center Copenhagen (Denmark). The inclusion criteria were age 30-70 years with either overweight (ie, BMI ≥25 kg/m2) and concomitant prediabetes (ie, glycated haemoglobin [HbA1c] 39-47 mmol/mol) or obesity (ie, BMI ≥30 kg/m2) with or without prediabetes and a habitual self-reported eating window (eating and drinking [except for water]) of 12 h per day or more every day and of 14 h per day or more at least 1 day per week. Individuals were randomly assigned 1:1 to 3 months of habitual living (hereafter referred to as the control group) or TRE, which was a self-selected 10-h per-day eating window placed between 0600 h and 2000 h. Randomisation was done in blocks varying in size and was open for participants and research staff, but outcome assessors were masked during statistical analyses. The randomisation list was generated by an external statistician. The primary outcome was change in bodyweight, assessed after 3 months (12 weeks) of the intervention and after 3 months (13 weeks) of follow-up. Adverse events were reported and registered at study visits or if participants contacted study staff to report events between visits. This trial is registered on ClinicalTrials.gov (NCT03854656). Between March 12, 2019, and March 2, 2022, 100 participants (66 [66%] were female and 34 [34%] were male; median age 59 years [IQR 52-65]) were enrolled and randomly assigned (50 to each group). Of those 100, 46 (92%) in the TRE group and 46 (92%) in the control group completed the intervention period. After 3 months of the intervention, there was no difference in bodyweight between the TRE group and the control group (-0·8 kg, 95% CI -1·7 to 0·2; p=0·099). Being in the TRE group was not associated with a lower bodyweight compared with the control group after subsequent 3-month follow-up (-0·2 kg, -1·6 to 1·2). In the per-protocol analysis, participants who completed the intervention in the TRE group lost 1·0 kg (-1·9 to -0·0; p=0·040) bodyweight compared with the control group after 3 months of intervention, which was not maintained after the 3-month follow-up period (-0·4 kg, -1·8 to 1·0). During the trial and follow-up period, one participant in the TRE group reported a severe adverse event: development of a subcutaneous nodule and pain when the arm was in use. This side-effect was evaluated to be related to the trial procedures. 3 months of 10-h per-day TRE did not lead to clinically relevant effects on bodyweight in middle-aged to older individuals at high risk of type 2 diabetes. Novo Nordisk Foundation, Aalborg University, Helsefonden, and Innovation Fund Denmark.

112 Flight Tracker: A REDCap Tool to Streamline Career Development Grant Preparation and Reporting

OBJECTIVES/GOALS: Compiling information about characteristics and progress of scholars is required for career development applications and progress reports. The range of information is substantial, and preparation is onerous. We sought to create a tool to facilitate gathering key data about trainees and mentors who participate in programs like NIH K- and T-awards. METHODS/STUDY POPULATION: Using the REDCap platform, we developed forms and surveys to support intake of applicants, updates from scholars, and information about their participation in activities and use of resources. We deployed application programming interfaces (APIs) to automate capture of publicly available data about publications, impact metrics, and federal grant funding. Similar tools capture descriptions of mentor expertise including grant funding, prior trainees, and publications with mentees We also built modules to 1) allow connection to institutional grant and contract data to capture foundation and other funding; 2) pre-populate follow-up surveys to update information about career trajectories with minimal scholar effort; and 3) support mentee-mentor agreements as living documents. RESULTS/ANTICIPATED RESULTS: After a pilot period at our institution, we disseminated Flight Tracker to more than 50 academic institutions, most of whom are CTSA hubs. They track scholars in TL1/T32s, KL2/K12s, MSTP programs, and academic groups. Beyond federal reporting, uses now include publication impact factors (relative citation ratios, Altmetrics scores), grant funding of groups, maps of network relationships among investigators, scholar receipt of internal pilot awards, and statistics about transition to independence and time-to-promotion. Scholars can be separated into smaller cohorts by demographics, training dates, and funding dates. Over 34,000 scholars are tracked nationally among over 260 programs. Having structured data supports program evaluation, continuous improvements, and documents program strengths. DISCUSSION/SIGNIFICANCE: We informally estimate Flight Tracker reduces staff and leadership effort in preparation of program data by 75%, preserving time to focus on service to scholars. Ready access to data over time and within and across institutions creates new opportunities for collaborative data analysis to support evidence-based career development.

Abstract 1426: Lipid-mediated epigenetic activation of PPAR-gamma signaling promotes immune-checkpoint resistance in hepatocellular carcinoma

Abstract Background: Although use of immune-checkpoint inhibitors (ICI) has yielded impressive results in cancer patients, resistance to ICI therapies has increasingly been observed, especially in hepatocellular carcinoma (HCC). Materials and Methods: We generated a novel anti-programmed death-ligand 1 (PD-L1) treatment resistant mouse hepatoma cell Hepa1-6 (PD-L1R) by 7-generation of in vivo selection. To dissect tumor cell-intrinsic resistant mechanism, we performed single-cell RNA-sequencing (scRNA-seq) from anti-PD-L1-treated tumors generated from parental or PD-L1R cells. Expression level of target genes was detected by QPCR, western blot and immunohistochemical analyses. Lipid content and fatty acid uptake was examined by Oil Red O and BIODIPY staining. Peroxisome proliferator-activated receptor gamma (PPARγ) promoter methylation level was analyzed by bisulfite pyrosequencing. To investigate the tumor cell-extrinsic factors, we profiled the myeloid and lymphoid lineages by flow cytometry. Results: ScRNA-seq revealed significant gene enrichments in lipid metabolism and PPARγ signaling pathway in PD-L1R tumors, which could be verified in both mRNA and protein levels. Moreover, we observed evident lipid accumulation in the PD-L1R tumors when compared to the parental tumors by Oil Red O staining. Consistently, PD-L1R tumor cells exhibited higher lipid content and enhanced fatty acid uptake in vitro, as demonstrated by BODIPY493/503 and BODIPY-C16 analyses. Of note, palmitic acid could dose-dependently increase Pparg mRNA expression in parental cells to a similar level with the PD-L1R cells, supporting an important role of lipids in inducing PPARγ expression. Pyrosequencing analysis indicated that PD-L1R cells exhibited lower PPARγ methylation level compared with parental cells. Notably, 5-Azacytidine treatment in parental cells significantly reduced the promoter DNA methylation and increased Pparg mRNA expression to similar extent with the PD-L1R tumor cells, thus indicating DNA hypomethylation-driven PPARγ up-regulation. Flow cytometry analysis showed that ICI resistance was associated with lower cytotoxic CD8+ T cells but higher intermediate Th17 cells, myeloid-derived suppressor cells and T regulatory cells in the tumor microenvironment (TME). Conclusions: Our study suggested that lipid exposure may epigenetically up-regulate PPARγ transcription in the development of anti-PD-L1 resistance. Detailed investigation on the crosstalk between aberrant lipid metabolism and immunosuppressive TME is ongoing. Acknowledgment: This study is supported by RGC General Research Fund (14120621 and 14119023), Li Ka Shing Foundation and CUHK Strategic Seed Funding for Collaborative Research Scheme. Citation Format: Zhewen Xiong, Stephen Lam Chan, Jingying Zhou, Xuezhen Zeng, Weiqin Yang, Haoran Wu, Jianquan Cao, Jie-Ting Low, Michael Wing-Yan Chan, Kevin Yuk-Lap Yip, Joseph Jao-Yiu Sung, Alfred Sze-Lok Cheng. Lipid-mediated epigenetic activation of PPAR-gamma signaling promotes immune-checkpoint resistance in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1426.

Abstract 2662: Deciphering the cellular and molecular determinants of immunotherapy resistance in NASH-associated hepatocellular carcinoma by single-cell analysis

Abstract Introduction: Non-alcoholic steatohepatitis (NASH) has emerged as a prominent risk and the most rapidly increasing aetiology of hepatocellular carcinoma (HCC). Despite the effectiveness of immune checkpoint blockade (ICB), like anti-programmed cell death-ligand 1 (anti-PD-L1) antibodies, in a subset of HCC patients, NASH has been shown to impair the anti-tumor immunity in ICB-treated HCC. We aim to elucidate the mechanisms responsible for ICB resistance in NASH-HCC at single-cell resolution. Methods: Orthotopic NASH-HCC mouse models were generated by orthotopically injecting liver cancer cell line into NASH liver induced by methionine-and choline-deficient diet (MCD) or choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Multi-color flow cytometry and single-cell RNA-sequencing (scRNA-seq) were utilized to dissect the liver and tumor immune microenvironment upon anti-PD-L1 treatment. Results: Anti-PD-L1 treatment failed to alleviate tumor burden in NASH mice, indicating that orthotopic NASH-HCC mouse models were resistant to ICB therapy. Compared to the control liver, multi-color flow cytometry demonstrated that CD11b+F4/80+CD206+M2 macrophages accumulated in NASH liver and further increased in liver and tumor upon anti-PD-L1 treatment. Tumor-infiltrating M2 macrophages exhibited the most significant and robust correlation with tumor weight among all immune cell types. Moreover, PD-1 expression on tumor-infiltrating CD8+ T cells positively correlated with tumor weight and intratumoral M2 macrophages. Furthermore, scRNA-seq analysis identified a NASH-specific tumor-infiltrating monocyte subcluster, which may differentiate into an ‘M2-like’ macrophage subtype upon anti-PD-L1 treatment as demonstrated by cell trajectory analysis. Conclusion: Our study provides insights into the significance of monocyte/macrophage reprogramming in ICB resistance in NASH-HCC. Further investigation is conducted to identify the molecular mechanisms during monocyte-macrophage differentiation and explore potential targeted strategies to overcome ICB resistance in NASH-HCC. Acknowledgment: This study is supported by the General Research Fund (14120621 and 14119023), the Collaborative Research Fund (C4045-18W), the Li Ka Shing Foundation and CUHK Strategic Seed Funding for Collaborative Research Scheme. Keywords: hepatocellular carcinoma, single-cell RNA-sequencing, anti-PD-L1, macrophages. Citation Format: Lingyun Zhang, Yiling Zhang, Wenshu Tang, Zhewen Xiong, Xiaoyu Liu, Zhixian Liang, Yuk Wah Tsang, Weiqin Yang, Xiaohang Long, Alfred Sze Lok Cheng. Deciphering the cellular and molecular determinants of immunotherapy resistance in NASH-associated hepatocellular carcinoma by single-cell analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2662.

Finding Creativity in Predictability: Seizing Kairos in Chronos Through Temporal Work in Complex Innovation Processes

Managing temporal complexity is a fundamental challenge in complex innovation processes, yet the temporal work whereby actors seize opportune moments (kairos) in an environment dominated by clock-time structures (chronos) remains elusive. Temporal tensions can partly be resolved through entrainment, that is, by aligning activities with dominant temporal structures. However, although entrainment ensures the exploitation of a predefined path, it is unable to harness unexpected developments as opportunities for exploration. Thus, navigating the competing temporal demands of chronos and kairos requires not just ambidextrous but also ambitemporal organizing. Collecting and analyzing in-depth interview and observational data from pharmaceutical drug discovery and development, we find that actors sometimes resolve temporal tensions through entrainment to ensure coordination and predictability. In other instances, however, actors abductively transform temporal tensions into novel interpretations and new courses of action. As such, temporal tensions become more than a bothersome deviation from the planned schedule, but an opportunity for creative agency. This understanding of kairos—as a process unfolding through temporal work—relies not only on detraining from chronos (i.e., momentarily detaching from the dominant temporal structure to question underlying assumptions), but also on its reframing and reconfiguration. We contribute to the literature on complex innovation and temporality by theorizing a transformative perspective on ambitemporal organizing, which relies less on paradoxical notions and instead emphasizes how kairos is enacted and seized within and from chronos. Funding: This work was supported by German Research Foundation (DFG) funding for the Research Unit “Organized Creativity” [Grant FOR 2161] as well as by the Austrian Science Fund (FWF) [10.55776/I4884].

Current global status of male reproductive health.

Current global status of male reproductive health.

“Making the Peaks Higher”: Foundations of Stanford University’s Growth, 1910–1960

This article breaks new ground in its portrayal of the process through which a private research university obtained foundation funding. Stanford University’s growth spurts after World War I and World War II were significantly enabled by financial support from the foundations of Carnegie, Rockefeller, and Ford. The process leading to Stanford’s receiving major grants primarily involved interactions among a small group of individuals and reflected the confidence of foundation presidents and other top administrators in the capacity of the university’s presidents and other leaders. The significance of such high-level interaction persisted even while major foundations professionalized, shifting responsibilities from trustees to staff. In the rendezvous between Stanford University and philanthropic foundations, these relationships mattered so much that at crucial junctures, funding to the university preceded expertise in the relevant field of study.

Analisis Laporan Keuangan Serta Tata Cara Pengelolaannya Pada Yayasan Galang Bersama Kami Sebagai Lembaga Filantropi Islam

The main objective of this research is to analyze the financial reports managed by the Galang Bersama Kami Foundation (YGBK) as a non-profit institution that focuses on raising funds from donors in the form of Zakat, Infaq, Alms and Waqf (ZISWAF) funds. Which is about where the Foundation's funds come from, and how the Foundation provides the allocation flow. For this purpose, the author used quantitative descriptive research methods, with direct observation techniques to related parties, followed by interviews and special documentation during data collection. After conducting interviews, the author found that the entire set of YGBK funds came from 3 things, namely from ZISWAF funds, CSR funds from agencies/companies, and potential businesses from our Joint Business Institutions. The funds raised will be channeled to the Foundation's program and operational funds, the distribution percentage of which is based on BAZNAS regulation Number 1 article 8 of 2016 specifically for ZISWAF funds. The percentage of CSR distribution depends on the Foundation's agreement with the CSR provider company. Meanwhile, the proceeds from our Joint Business will be distributed in full to the Foundation's operational costs. The percentage of the Foundation's financial reports shows a decrease in income from 2022 to 2023 of 49%. All of this is done to provide transparent and open financial management for the people in order to maintain their sense of trust in the Galang Bersama Kami Foundation.