bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the COVID-19 pandemic on timeliness and equity of measles, mumps and rubella vaccinations in North East London: a longitudinal study using electronic health records
Authors: Firman Nicola , Marszalek Milena , Gutierrez Ana , Homer Kate , Williams Crystal , Harper Gill , Dostal Isabel , Ahmed Zaheer , Robson John , Dezateux Carol 
Published: December 2022

ObjectivesTo quantify the effect of the COVID-19 pandemic on the timeliness of, and geographical and sociodemographic inequalities in, receipt of first measles, mumps and rubella (MMR) vaccination.DesignLongitudinal study using primary care electronic health records.Setting285 general practices in North East London.ParticipantsChildren born between 23 August 2017 and 22 September 2018 (pre-pandemic cohort) or between 23 March 2019 and 1 May 2020 (pandemic cohort).Main outcome measureReceipt of timely MMR vaccination between 12 and 18 months of age.MethodsWe used logistic regression to estimate the ORs (95% CIs) of receipt of a timely vaccination adjusting for sex, deprivation, ethnic background and Clinical Commissioning Group. We plotted choropleth maps of the proportion receiving timely vaccinations.ResultsTimely MMR receipt fell by 4.0% (95% CI: 3.4% to 4.6%) from 79.2% (78.8% to 79.6%) to 75.2% (74.7% to 75.7%) in the pre-pandemic (n=33 226; 51.3% boys) and pandemic (n=32 446; 51.4%) cohorts, respectively. After adjustment, timely vaccination was less likely in the pandemic cohort (0.79; 0.76 to 0.82), children from black (0.70; 0.65 to 0.76), mixed/other (0.77; 0.72 to 0.82) or with missing (0.77; 0.74 to 0.81) ethnic background, and more likely in girls (1.07; 1.03 to 1.11) and those from South Asian backgrounds (1.39; 1.30 to 1.48). Children living in the least deprived areas were more likely to receive a timely MMR (2.09; 1.78 to 2.46) but there was no interaction between cohorts and deprivation (Wald statistic: 3.44; p=0.49). The proportion of neighbourhoods where less than 60% of children received timely vaccination increased from 7.5% to 12.7% during the pandemic.ConclusionsThe COVID-19 pandemic was associated with a significant fall in timely MMR receipt and increased geographical clustering of measles susceptibility in an area of historically low and inequitable MMR coverage. Immediate action is needed to avert measles outbreaks and support primary care to deliver timely and equitable vaccinations.
Methamphetamine-associated heart failure: a systematic review of observational studies
Authors: Manja Veena , Nrusimha Ananya , Gao Ya , Sheikh Aleesha , McGovern Mark , Heidenreich Paul A , Sandhu Alex Tarlochan Singh , Asch Steven 
Published: December 2022

ObjectiveTo conduct a systematic review of observational studies on methamphetamine-associated heart failure (MethHF) .MethodsSix databases were searched for original publications on the topic. Title/abstract and included full-text publications were reviewed in duplicate. Data extraction and critical appraisal for risk of bias were performed in duplicate.ResultsTwenty-one studies are included in the final analysis. Results could not be combined because of heterogeneity in study design, population, comparator, and outcome assessment. Overall risk of bias is moderate due to the presence of confounders, selection bias and poor matching; overall certainty in the evidence is very low. MethHF is increasing in prevalence, affects diverse racial/ethnic/sociodemographic groups with a male predominance; up to 44% have preserved left-ventricular ejection fraction. MethHF is associated with significant morbidity including worse heart failure symptoms compared with non-methamphetamine related heart failure. Female sex, methamphetamine abstinence and guideline-directed heart failure therapy are associated with improved outcomes. Chamber dimensions on echocardiography and fibrosis on biopsy predict the extent of recovery after abstinence.ConclusionsThe increasing prevalence of MethHF with associated morbidity underscores the urgent need for well designed prospective studies of people who use methamphetamine to accurately assess the epidemiology, clinical features, disease trajectory and outcomes of MethHF. Methamphetamine abstinence is an integral part of MethHF treatment; increased availability of effective non-pharmacological interventions for treatment of methamphetamine addiction is an essential first step. Availability of effective pharmacological treatment for methamphetamine addiction will further support MethHF treatment. Using harm reduction principles in an integrated addiction/HF treatment programme will bolster efforts to stem the increasing tide of MethHF.
$${\textbf{D}}$$-dimensional dyonic AdS black holes with quasi-topological electromagnetism in Einstein Gauss–Bonnet gravity
Authors: Sekhmani Yassine , Lekbich Hicham , El Boukili Abderrahman , Sedra Moulay Brahim 
Published: December 2022

AbstractWithin Gauss–Bonnet gravity, we construct a solution endowed with dyonic matter fields in a higher dimension. The quasi-topological electromagnetism generates two kinds of contributions; one is the kinetic terms, and the second refers to the interactif terms. This overcomes the invariance topological problem. We investigate the thermodynamical proprieties of the obtained solution, namely,ADMmass, Hawking temperature, and entropy. To inspect the local stability, we examine the associated heat capacity. With regards to optical proprieties, we analyze the null geodesic in terms of the given parameter space. The shadow radius is a generating form with all the physical parameters that govern the shadow behavior. The study restricts only the taking of the effects of theDand$$\alpha $$αparameters. Finally, we examine the impact of the dimensionD,GBcoupling constant$$\alpha $$α, the cosmological constant$$\Lambda $$Λ, the electric$$q_e$$qe, the magnetic charge$$q_m$$qmand the coupling constant$$\beta $$βon the energy emission rate.
The impact of the National Science Foundation’s Innovation Corps (I-Corps) on academic innovation and entrepreneurship
Authors: Schultz Ivy , Blaho John A. , Becker Kurt H. 
Published: December 2022

Abstract
In 2011, the U.S. National Science Foundation created the Innovation Corps (I-Corps) program in an effort to explore ways to translate the results of the academic research the agency has funded into new products, processes, devices, or services and move them to the marketplace. The agency established a 3-tier structure to support the implementation of the I-Corps concept. Selected I-Corps teams consisting of the principal investigator, an entrepreneurial lead, and an industry mentor participate in a 7-week accelerated version of the Lean Launchpad methodology that was first developed by Steve Blank at Stanford University. Participating teams engage in talking to potential customers, partners, and competitors and address the challenges and the uncertainty of creating successful ventures. I-Corps sites were set up to promote selected aspects of innovation and entrepreneurship ecosystems at the grantee institutions. I-Corps Regional Nodes were charged with recruiting I-Corps teams in a larger geographical area as well as stimulating a new culture of academic entrepreneurship in the institutions in their area of influence. This Topical Review describes the experiences and the impact of the New York City Regional Innovation Node, which is led by the City University of New York, in partnership with New York University and Columbia University.

Graphic abstract
Do Mutual Funds Reward Downside Risk? Evidence from an Emerging Economy
Authors: Agarwal Pankaj K. , Pradhan H. K. 
Published: December 2022

The increasing participation of retail investors — generally having limited risk bearing ability — in mutual funds, has surprisingly not motivated rigorous examination of downside risks-forward return relationship of these funds, which this study aims to accomplish. We use a survivorship-bias free database of returns and portfolio holdings of Indian equity mutual funds covering the period April 2008–November 2018 with Cornish–Fisher expansion of Value-at-Risk (VaR) as a measure of downside risk to examine downside risk-forward return relationship controlling for the fund characteristics such as age, size and style. To complete the story, we also test for the presence of Downside Risk Timing (DRT) ability of fund managers. We find that downside risk does predict future returns of mutual funds and the result holds across different fund sizes, age and styles, particularly strongly in large and midcap style. We also find that the fund manager of the median fund exhibits positive DRT at the 1- and 6-month horizons and negative at the 3- and 12-month horizons. The mixed evidence on DRT suggests that fund managers either did not possess the requisite risk-timing ability or had failed in its application. Findings have important implications for both investors and fund managers.
A Time and Place for Inhibiting Autophagy
Authors: Gan Boyi 
Published: December 2022

AbstractAutophagy is an attractive therapeutic target in cancer. Successful autophagy-focused clinical intervention will require a detailed understanding of when and where autophagy is important during tumorigenesis. In this issue of Cancer Research, Khayati and colleagues use state-of-the-art genetically engineered mouse models to demonstrate that transient systemic inhibition of autophagy can irreversibly impair the growth of established lung tumors with a good tolerability in normal tissues, suggesting a therapeutic strategy for cancer treatment.See related article by Khayati et al., p. 4429
Discovery of STRO-002, a Novel Homogeneous ADC Targeting Folate Receptor Alpha, for the Treatment of Ovarian and Endometrial Cancers
Authors: Li Xiaofan , Zhou Sihong , Abrahams Cristina L. , Krimm Stellanie , Smith Jennifer , Bajjuri Krishna , Stephenson Heather T. , Henningsen Robert , Hanson Jeffrey , Heibeck Tyler H. , Calarese Daniel , Tran Cuong , Yin Gang , Stafford Ryan L. , Yam Alice Y. , Kline Toni , De Almeida Venita I. , Sato Aaron K. , Lupher Mark , Bedard Kristin , Hallam Trevor J. 
Published: December 2022

AbstractSTRO-002 is a novel homogeneous folate receptor alpha (FolRα) targeting antibody–drug conjugate (ADC) currently being investigated in the clinic as a treatment for ovarian and endometrial cancers. Here, we describe the discovery, optimization, and antitumor properties of STRO-002. STRO-002 was generated by conjugation of a novel cleavable 3-aminophenyl hemiasterlin linker-warhead (SC239) to the nonnatural amino acid para-azidomethyl-L-phenylalanine incorporated at specific positions within a high affinity anti-FolRα antibody using Sutro's XpressCF+, which resulted in a homogeneous ADC with a drug–antibody ratio (DAR) of 4. STRO-002 binds to FolRα with high affinity, internalizes rapidly into target positive cells, and releases the tubulin-targeting cytotoxin 3-aminophenyl hemiasterlin (SC209). SC209 has reduced potential for drug efflux via P-glycoprotein 1 drug pump compared with other tubulin-targeting payloads. While STRO-002 lacks nonspecific cytotoxicity toward FolRα-negative cell lines, bystander killing of target negative cells was observed when cocultured with target positive cells. STRO-002 is stable in circulation with no change in DAR for up to 21 days and has a half-life of 6.4 days in mice. A single dose of STRO-002 induced significant tumor growth inhibition in FolRα-expressing xenograft models and patient-derived xenograft models. In addition, combination treatment with carboplatin or Avastin further increased STRO-002 efficacy in xenograft models. The potent and specific preclinical efficacy of STRO-002 supports clinical development of STRO-002 for treating patients with FolRα-expressing cancers, including ovarian, endometrial, and non–small cell lung cancer. Phase I dose escalation for STRO-002 is in progress in ovarian cancer and endometrial cancer patients (NCT03748186 and NCT05200364).
Abstract A022: A field survey of histone PTM antibodies in epigenomic mapping approaches reveals widespread liabilities: Best practices and resources for reliable epigenetic studies
Authors: Johnstone Andrea L. , Maryanski Danielle N. , Rodriguez Keli L. , Weinzapfel Ellen N. , Venters Bryan J. , Novitzky Katherine , Marunde Matthew R. , Lin Carolina P. , Keogh Michael-Christopher 
Published: December 2022

Abstract
Histone post-translational modifications (PTMs) play a critical role in chromatin regulation. It has long been suspected that the poorly understood capability of ‘PTM-specific’ antibodies (i.e., their specificity and efficiency) is a prime driver of the reproducibility crisis in biomedical research. Here we confirm the validity of this concern as it applies to epigenomic mapping studies. Extensive spike-in panels of PTM-defined DNA-barcoded nucleosome standards show that &gt;70% of &gt;500 commercial antibodies (and &gt;80% of the most highly cited) to &gt;50 histone lysine methyl and acyl states have failing performance in ChIP (&gt;20% cross reactivity/&lt;5% target recovery; www.ChromatinAntibodies.com). Variable lot behavior (of both polyclonals and monoclonals) shows the danger of focusing on catalog numbers without considering the inherent variability of biological reagents. Ultimately, these studies support the inclusion of in situ standards to control genomic mapping assays as an improved path out of this morass. Despite these advances, the application of ChIP-seq for cancer research has been hampered by its requirement for high cell inputs and low reliability. The recent development of immunotethering assays, such as Cleavage Under Targets and Release Using Nuclease (CUT&RUN), deliver high signal-to-noise mapping data using a fraction of the required cells compared to ChIP-seq. These innovations enable the application of epigenomics for cancer research, particularly for primary cells, sorted populations, and clinical samples where cell numbers are limited. By adapting our nucleosome spike-in control approach for CUT&RUN assays, we show that while the same antibody problems observed in ChIP-seq also pervade CUT&RUN, continuous use of spike-in controls improves assay rigor and reproducibility to realize the potential of CUT&RUN to advance cancer research.
Citation Format: Andrea L. Johnstone, Danielle N. Maryanski, Keli L. Rodriguez, Ellen N. Weinzapfel, Bryan J. Venters, Katherine Novitzky, Matthew R. Marunde, Carolina P. Lin, Michael-Christopher Keogh. A field survey of histone PTM antibodies in epigenomic mapping approaches reveals widespread liabilities: Best practices and resources for reliable epigenetic studies. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Epigenomics; 2022 Oct 6-8; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_2):Abstract nr A022.
Abstract A024: PRC2 loss drives MPNST metastasis and matrix remodeling
Authors: Brockman Qierra R. , Scherer Amanda , McGivney Gavin R. , Gutierrez Wade R. , Voigt Andrew , Isaacson Alexandra , Laverty Emily A. , Roughton Grace , Knepper-Adrian Vickie , Darbro Benjamin , Tanas Munir R. , Stipp Christopher , Dodd Rebecca D. 
Published: December 2022

Abstract
Epigenetic reprogramming alters gene transcription in response to different cellular cues and can occur at both the DNA level as well as histone post-translational modifications. Polycomb repressive complex 2 (PRC2) is a common epigenetic modifier that is responsible for adding methyl groups to the twenty-seventh lysine of histone 3. This modification is associated with decreased gene transcription and recruits complexes that further compact chromatin. PRC2 mutations have been implicated in the tumorigenesis of many cancer types; however, the role that PRC2 plays in tumorigenesis is complex and not well understood. PRC2 loss-of-function mutations have been identified in malignant peripheral nerve sheath tumors (MPNST), an aggressive sarcoma. PRC2 mutations are found in the EED and SUZ12 subunits in 70-92% of tumors. There are currently no effective therapies for MPNSTs resulting in a poor prognosis for individuals with inoperable tumors. Using a CRISPR/Cas9 system to delete EED or SUZ12, we developed in vitro and in vivo models to further study the biology of PRC2 loss in MPNSTs. Our data suggests that loss of PRC2 subunits increases the expression of extra-cellular matrix (ECM) remodeling genes, promotes cell migration in vitro, and increases pulmonary metastasis in vivo. We also observed that loss of either EED or SUZ12 increases collagen handling and a clustering metastatic phenotype. Additionally, loss of H3K27me3 was correlated with increased ECM and ECM remodeling genes as well as metastasis and overall survival in patient RNA-seq and tumor microarray data, respectively. Further characterization of the underlying mechanisms of PRC2-dependent metastasis will allow us to better understand the role of PRC2 in MPNST biology and test novel therapies for these patients.
Citation Format: Qierra R. Brockman, Amanda Scherer, Gavin R. McGivney, Wade R. Gutierrez, Andrew Voigt, Alexandra Isaacson, Emily A. Laverty, Grace Roughton, Vickie Knepper-Adrian, Benjamin Darbro, Munir R. Tanas, Christopher Stipp, Rebecca D. Dodd. PRC2 loss drives MPNST metastasis and matrix remodeling. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Epigenomics; 2022 Oct 6-8; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_2):Abstract nr A024.
Abstract A027: Identification and role of mega-trans-factors in epithelial ovarian cancer
Authors: Jaiswal Sushil Kumar , Fedkenheuer Kevin , Elnitski Laura 
Published: December 2022

Abstract
Epithelial ovarian cancer (EOC) accounts for over 90% of ovarian cancer cases and results in 14,000 U.S. deaths annually. It is the leading cause of death attributed to gynecological cancers. Aside from recent scientific advances, the 5-year survival rate for late-stage invasive EOC has been near 30% for several decades. Our computational transcriptional regulatory analysis in low-grade serous ovarian cancers (LGSOCs) vs. high-grade serous ovarian cancers (HGSOCs) identified a master regulatory complex, Megatrans complex (MTC), the objective of this study is to identify role of MTC in ovarian cancer, never reported before. MTC is estrogen-responsive master regulatory complex containing a multitude of DNA-binding transcription factors (MTC_TFs), including ER-alpha, RAR-alpha, GATA3, AP2-gamma, STAT1, AP1, RUNX1, and FOXA1. Given that we found MTC gene targets are downregulated in HGSOC, and that some target genes are prognostic for poor patient survival, understanding the function of MTC and modulating its activity may improve prognostic outcomes for HGSOC patients. We hypothesize that different combinations of MTC_TFs produce distinct regulatory signatures in different grades of ovarian cancers. In the grade, PEO4, cell line, we have confirmed MTC formation using a gel filtration assay and identified the presence of MTC_TFs by western blot. We discovered tumor suppressor, PITX1, as a novel MTC_TF in ovarian cancer, not previously reported in a breast cancer MTC. Methylation analysis revealed PITX1 and ER-alpha binding to hypomethylated, but repressed promoters and ChIP-seq analysis revealed PITX1 co-occupying 98.8% of ER-alpha binding sites, suggesting a repressive role of PITX1 on ER-alpha regulated genes. We are performing additional ChIP-seq experiments of MTC_TFs in HGSOC and LGSOC cell lines to test whether the MTC_TF binding distinguishes their regulatory signatures. Our findings of a nuclear hormone-regulated MTC complex controlling the transcriptional landscape of ovarian cancer are expected to facilitate new breakthroughs in disease treatment.
Citation Format: Sushil Kumar Jaiswal, Kevin Fedkenheuer, Laura Elnitski. Identification and role of mega-trans-factors in epithelial ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Epigenomics; 2022 Oct 6-8; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_2):Abstract nr A027.
Abstract IA014: SWI/SNF complexes in development and disease
Authors: Gatchalian Jovylyn , Ahmed Nasiha , Loo Chin-San , Zheng Ye , Hargreaves Diana C. 
Published: December 2022

Abstract
The Hargreaves laboratory is focused on understanding the molecular mechanisms of SWI/SNF complex function in immune cell differentiation and response relating to cancer and inflammation. SWI/SNF complexes are broadly required for embryonic development and cellular differentiation. Mutations in SWI/SNF complex genes are observed in ~20% of human cancers and in a number of rare intellectual disability disorders. However, it remains unclear how SWI/SNF complexes mechanistically regulate cellular differentiation through complex targeting, engagement with transcription factors, and function in transcription. We approach these questions in immune cells by employing molecular and proteomic methods in conjunction with next-generation sequencing approaches with the ultimate goal of connecting the functions of specific SWI/SNF subunits to the regulation of specific gene networks important for inflammatory responses and immune cell differentiation. This approach has allowed us to reveal the role of the canonical BAF complex (cBAF) in the establishment and maintenance of epigenetic transitions that occur during cellular differentiation, including activation of cell type-specific enhancers and engagement of transcription factors. Further, we and others have identified a new variant, referred to as the noncanonical BAF (ncBAF) complex, which exhibits distinct modes of targeting, unique regulatory interactions, and specific function in inflammatory gene transcription (Ahmed, Gatchalian et al PNAS 2022). Following up on the identification of the ncBAF subunit Brd9 in a CRISPR genome wide screen for regulators of Foxp3 performed in collaboration with the Zheng lab at the Salk Institute, we performed sgRNA knockdown to identify the role of each of the three SWI/SNF complex variants (BAF, ncBAF, and PBAF) (Loo, Gatchalian et al Immunity 2020). We found that ncBAF positively regulates the expression of Foxp3, while PBAF complexes negatively regulate Foxp3. Using epigenomic and transcriptomic analysis in Tregs following knockdown or chemical degradation of BRD9, we found that BRD9 positively regulates Foxp3 expression and its target genes by stabilizing Foxp3 binding at BRD9/Foxp3 co-bound sites, including at the Foxp3 locus. In an MC38 colorectal cancer model, transfer of Brd9 deficient Tregs resulted in significantly slower tumor growth than control Tregs, with increased infiltration of IFN-γ producing CD8 and CD4 T cells, suggesting that Brd9 deletion in Tregs reduces Treg-mediated suppression of anti-tumor responses. Thus, these results highlight BRD9 and the ncBAF complex as novel targets that could be exploited to manipulate Treg function in cancer.
Citation Format: Jovylyn Gatchalian, Nasiha Ahmed, Chin-San Loo, Ye Zheng, Diana C. Hargreaves. SWI/SNF complexes in development and disease. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Epigenomics; 2022 Oct 6-8; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_2):Abstract nr IA014.