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The new-generation atmospheric environment monitoring satellite DQ-1, launched successfully in April 2022, carries the Aerosol and Carbon Detection Lidar (ACDL), which is capable of globally profiling aerosol and cloud optical properties with high accuracy. The ACDL/DQ-1 is a high-spectral-resolution lidar (HSRL) that separates molecular backscatter signals using an iodine filter and has 532 nm polarization detection and dual-wavelength detection at 532 and 1064 nm, which can be utilized to derive aerosol optical properties. The methods have been specifically developed for data processing and optical property retrieval according to the specific characteristics of the ACDL system and are introduced in detail in this paper. Considering the different signal characteristics and different background noise behaviors of each channel during daytime and nighttime, the procedures of data pre-processing, denoising process and quality control are applied to the original measurement signals. The aerosol and cloud optical property products of the ACDL/DQ-1, including the total depolarization ratio, backscatter coefficient, extinction coefficient, lidar ratio and color ratio, can be calculated by the retrieval algorithms presented in this paper. Two measurement cases with use of the ACDL/DQ-1 on 27 June 2022 and the global averaged aerosol optical depth (AOD) from 1 June to 4 August 2022 are provided and analyzed, demonstrating the measurement capability of the ACDL/DQ-1.

Reactivation of pre-existing structures and their influence on subsequent rift evolution have been extensively analysed in previous research on rifts that experienced multiple phases of rifting, where pre-existing structures were deemed to affect nucleation, density, strike orientation, and displacement of newly formed normal faults during later rifting stages. However, previous studies paid less attention to the extensional structures superimposing onto an earlier compressional background, leading to a lack of understanding of, e.g. the reactivation and growth pattern of pre-existing thrust faults as low-angle normal faults and the impact of pre-existing thrust faults on newly formed high-angle faults and subsequent rift structures. This study investigating the spatial relationship between intra-basement thrust and rift-related faults in the Enping sag, in the northern South China Sea, indicates that the rift system is built on the previously deformed basement with pervasive thrusting structures and that the low-angle major fault of the study area results from reactivation of intra-basement thrust faults. It also implies that the reactivation mode of basement thrust faults is dependent on the overall strain distribution across rifts, the scale of basement thrust faults, and the strain shadow zone. In addition, reactivated basement thrust faults influence the nucleation, dip, and displacement of nearby new faults, causing them to nucleate at or merge into downwards it, which is representative of the coupled and decoupled growth models of reactivated thrust faults and nearby new faults. This work not only provides insights into the growth pattern of rift-related faults interacting with reactivated low-angle faults but also has broader implications for how basement thrust faults influence rift structures, normal fault evolution, and syn-rift stratigraphy.

Utilization of telehealth in school-based health centers (SBHCs) is increasing rapidly during the COVID-19 pandemic. This study used a quasi-experimental design to evaluate the effect on school absences and cost-benefit of telehealth-exclusive SBHCs at 6 elementary schools from 2015-2017. The effect of telehealth on absences was estimated compared to students without telehealth using negative binomial regression controlling for absences and health suite visits in 2014 and sociodemographic characteristics. The sample included 7,164 observations from 4,203 students. Telehealth was associated with a 7.7% (p = 0.025; 95% CI: 1.0%, 14%) reduction in absences (0.60 days/year). The program cost $189,000/yr and an estimated total benefit of $384,995 (95% CI: $60,416; $687,479) and an annual net benefit of $195,873 (95% CI: -$128,706; $498,357). While this cost-benefit analysis is limited by a lack of data on total healthcare utilization, the use of telehealth-exclusive SBHCs can improve student health and attendance while delivering cost savings to society.

Summary: We previously described that the KDM5B histone H3 lysine 4 demethylase is an oncogene in estrogen-receptor-positive breast cancer. Here, we report that KDM5A is amplified and overexpressed in basal breast tumors, and KDM5 inhibition (KDM5i) suppresses the growth of KDM5-amplified breast cancer cell lines. Using CRISPR knockout screens in a basal breast cancer cell line with or without KDM5i, we found that deletion of the ZBTB7A transcription factor and core SAGA complex sensitizes cells to KDM5i, whereas deletion of RHO-GTPases leads to resistance. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed co-localization of ZBTB7A and KDM5A/B at promoters with high histone H3K4me3 and dependence of KDM5A chromatin binding on ZBTB7A. ZBTB7A knockout altered the transcriptional response to KDM5i at NF-κB targets and mitochondrion-related pathways. High expression of ZBTB7A in triple-negative breast cancer is significantly associated with poor response to neoadjuvant chemotherapy. Our work furthers the understanding of KDM5-mediated gene regulation and identifies mediators of sensitivity to KDM5i.

The role of MYC in transcriptional reprogramming in prostate cancer remains poorly characterized. Here, MYC overexpression antagonizes the canonical AR transcriptional program leading to prostate tumor initiation and progression by disrupting transcriptional pause release at AR-regulated genes.

HER2+ breast cancer often develop brain metastases (BCBMs) that are difficult to treat. Here, the authors show that p16INK4A loss in BCBMs from HER2+ breast tumors results in resistance to the HER2 inhibitor Tucatinib, and that CDK4/6 inhibition can restore sensitivity to this drug.

Wildland fires are a major source of gases and aerosols, and the production, dispersion, and transformation of fire emissions have significant ambient air quality impacts and climate interactions. The increase in wildfire area burned and severity across the United States and Canada in recent decades has led to increased interest in expanding the use of prescribed fires as a forest management tool. While the primary goal of prescribed fire use is to limit the loss of life and property and ecosystem damage by constraining the growth and severity of future wildfires, a potential additional benefit of prescribed fire - reduction in the adverse impacts of smoke production and greenhouse gas (GHG) emissions - has recently gained the interest of land management agencies and policy makers in the United States and other nations. The evaluation of prescribed fire/wildfire scenarios and the potential mitigation of adverse impacts on air quality and GHGs requires fuel layer specific pollutant emission factors (EFs) for fire prone forest ecosystems. Our study addresses this need with laboratory experiments measuring EFs for carbon dioxide (CO2), carbon monoxide (CO), methane (CH4), ethyne (C2H2), formaldehyde (H2CO), formic acid (CH2O2), hydrogen cyanide (HCN), fine particulate matter (PM2.5), nitric oxide (NO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and total reduced sulfur (TRS) for the burning of individual fuel components from three forest ecosystems which account for a large share of wildfire burned area and emissions in the western United States and Canada - Douglas fir, ponderosa pine, and black spruce/jack pine.

Abstract Background To reduce the prevalence of anemia, the Indian government recommends daily iron and folic acid supplements (iron supplements) for pregnant women and weekly iron supplements for adolescents and all women of reproductive age. The government has distributed free iron supplements to adolescents and pregnant women for over four decades. However, initial uptake and adherence remain inadequate and non-pregnant women of reproductive age are largely ignored. The aim of this study is to examine the multilevel barriers to iron supplement use and to subsequently identify promising areas to intervene. Methods We conducted a qualitative study in the state of Odisha, India. Data collection included key informant interviews, focus group discussions with women, husbands, and mothers-in-law, and direct observations in health centers, pharmacies and village health and nutrition days. Results We found that at the individual level, participants knew that iron supplements prevent anemia but underestimated anemia prevalence and risk in their community. Participants also believed that taking too many iron supplements during pregnancy would “make your baby big” causing a painful birth and a costly cesarean section. At the interpersonal level, mothers-in-law were not supportive of their daughters-in-law taking regular iron supplements during pregnancy but husbands were more supportive. At the community level, participants reported that only pregnant women and adolescents are taking iron supplements, ignoring non-pregnant women altogether. Unequal gender norms are also an upstream barrier for non-pregnant women to prioritize their health to obtain iron supplements. At the policy level, frontline health workers distribute iron supplements to pregnant women only and do not follow up on adherence. Conclusions Interventions should address multiple barriers to iron supplement use along the socio-ecological model. They should also be tailored to a woman’s reproductive life course stage: adolescents, pregnancy, and non-pregnant women of reproductive age because social norms and available services differ between the subpopulations.

ObjectivesTo examine whether the demographics of providers' prior year patient cohorts, providers' historic degree of catheter-based fractional flow reserve (FFR) utilization, and other provider characteristics were associated with post-catheterization performance of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).Study designA retrospective, observational analysis of outpatient claims data was performed.MethodsAll 2018 outpatient catheterization claims from a national organization offering commercial and Medicare Advantage health plans were examined. Claims were excluded if the patient had a prior catheterization in 2018, had any indications of CABG or valvular heart disease in the prior year of claims, or if the provider had ≤10 catheterization claims in 2017. Downstream PCI and CABG were determined by examining claims 0-30 days post-catheterization. Using multivariate mixed effects logistic regression with provider identity random effects, the association between post-catheterization procedures and provider characteristics was assessed, controlling for patient characteristics.ResultsThe sample consisted of 31,920 catheterization claims pertaining to procedures performed by 964 providers. Among the catheterization claims, 8,554 (26.8%) were followed by PCI and 1,779 (5.6%) were followed by CABG. Catheterizations performed by providers with older prior year patient cohorts were associated with higher adjusted odds of PCI (1.78; CI: 1.26-2.53), even after controlling for patient age. Catheterizations performed by providers with greater historic use of FFR had significantly higher adjusted odds of being followed by PCI (1.73; CI: 1.26-2.37).ConclusionProvider characteristics may impact whether patients receive a procedure post-catheterization. Further research is needed to characterize this relationship.

Motivation: The chromatin profile measured by ATAC-seq, ChIP-seq, or DNase-seq experiments can identify genomic regions critical in regulating gene expression and provide insights on biological processes such as diseases and development. However, quality control and processing chromatin profiling data involves many steps, and different bioinformatics tools are used at each step. It can be challenging to manage the analysis. Results: We developed a Snakemake pipeline called CHIPS (CHromatin enrIchment ProcesSor) to streamline the processing of ChIP-seq, ATAC-seq, and DNase-seq data. The pipeline supports single- and paired-end data and is flexible to start with FASTQ or BAM files. It includes basic steps such as read trimming, mapping, and peak calling. In addition, it calculates quality control metrics such as contamination profiles, polymerase chain reaction bottleneck coefficient, the fraction of reads in peaks, percentage of peaks overlapping with the union of public DNaseI hypersensitivity sites, and conservation profile of the peaks. For downstream analysis, it carries out peak annotations, motif finding, and regulatory potential calculation for all genes. The pipeline ensures that the processing is robust and reproducible. Availability: CHIPS is available at https://github.com/liulab-dfci/CHIPS.

Summary: Sustained treatment of estrogen receptor (ER)-positive breast cancer with ER-targeting drugs results in ER mutations and refractory unresponsive cancers. Androgen receptor (AR), which is expressed in 80%–95% of ER-positive breast cancers, could serve as an alternate therapeutic target. Although AR agonists were used in the past to treat breast cancer, their use is currently infrequent due to virilizing side effects. Discovery of tissue-selective AR modulators (SARMs) has renewed interest in using AR agonists to treat breast cancer. Using translational models, we show that AR agonist and SARM, but not antagonist, inhibit the proliferation and growth of ER-positive breast cancer cells, patient-derived tissues, and patient-derived xenografts (PDX). Ligand-activated AR inhibits wild-type and mutant ER activity by reprogramming the ER and FOXA1 cistrome and rendering tumor growth inhibition. These findings suggest that ligand-activated AR may function as a non-canonical inhibitor of ER and that AR agonists may offer a safe and effective treatment for ER-positive breast cancer. : Molecular Biology; Molecular Mechanism of Gene Regulation; Cancer Subject Areas: Molecular Biology, Molecular Mechanism of Gene Regulation, Cancer

Summary: Long noncoding RNAs (lncRNAs) have emerged as critical regulators of tumorigenesis, and yet their mechanistic roles remain challenging to characterize. Here, we integrate functional proteomics with lncRNA-interactome profiling to characterize Urothelial Cancer Associated 1 (UCA1), a candidate driver of ovarian cancer development. Reverse phase protein array (RPPA) analysis indicates that UCA1 activates transcription coactivator YAP and its target genes. In vivo RNA antisense purification (iRAP) of UCA1 interacting proteins identified angiomotin (AMOT), a known YAP regulator, as a direct binding partner. Loss-of-function experiments show that AMOT mediates YAP activation by UCA1, as UCA1 enhances the AMOT-YAP interaction to promote YAP dephosphorylation and nuclear translocation. Together, we characterize UCA1 as a lncRNA regulator of Hippo-YAP signaling and highlight the UCA1-AMOT-YAP signaling axis in ovarian cancer development. : Cancer Systems Biology; Omics; Proteomics; Systems Biology Subject Areas: Cancer Systems Biology, Omics, Proteomics, Systems Biology

Summary Introduction This report presents a synopsis of a three‐part, cross‐sector, seminar series held at the George Washington University (GWU) in Washington, DC from February–April, 2018. The overarching goal of the seminar series was to provide a neutral forum for diverse stakeholders to discuss and critically evaluate approaches to address added sugar intake, with a key focus on the role of low‐calorie sweeteners (LCS). Methods During three seminars, twelve speakers from academic institutions, federal agencies, non‐profit organizations, and the food and beverage industries participated in six interactive panel discussions to address: 1) Do Farm Bill Policies Impact Population Sugar Intake? 2) What is the Impact of Sugar‐sweetened Beverage (SSB) Taxes on Health and Business? 3) Is Sugar Addictive? 4) Product Reformulation Efforts: Progress, Challenges, and Concerns? 5) Low‐calorie Sweeteners: Helpful or Harmful, and 6) Are Novel Sweeteners a Plausible Solution? Discussion of each topic involved brief 15‐minute presentations from the speakers, which were followed by a 25‐minute panel discussion moderated by GWU faculty members and addressed questions generated by the audience. Sessions were designed to represent opposing views and stimulate meaningful debate. Given the provocative nature of the seminar series, attendee questions were gathered anonymously using Pigeonhole™, an interactive, online, question and answer platform. Results This report summarizes each presentation and recapitulates key perspectives offered by the speakers and moderators. Conclusions The seminar series set the foundation for robust cross‐sector dialogue necessary to inform meaningful future research, and ultimately, effective policies for lowering added sugar intakes.

Across the United States, wildfire severity and frequency are increasing, placing many properties at risk of harm or destruction. We quantify and compare how different forest management strategies designed to increase forest resilience and health reduce the number of properties at risk from wildfire, focusing on the Lake Tahoe Basin of California and Nevada. We combine landscape change simulations (including climate change, wildfire, and management effects) with scenarios of current and plausible fuel treatment activities and parcel-scale fire risk analysis. Results suggest that more aggressive fuel treatment activities that treat more area on the landscape, whether through mechanical and hand thinning or prescribed fire, dramatically lower the fire probability in the region and lead to a corresponding lower risk of property loss. We estimate that relative to recent practices of focusing management in the wildland–urban interface, more active forest management can reduce property loss risk by 45%–76%, or approximately 2600–4900 properties. The majority of this risk reduction is for single family residences, which constitute most structures in the region. Further, we find that the highest risk reduction is obtained through strategies that treat a substantially greater area than is currently treated in the region and allows for selective wildfires to burn for resource objectives outside of the wildland–urban interface. These results highlight the importance of more active forest management as an effective tool in reducing the wildfire risk to capital assets in the region.

Land managers in the Lake Tahoe basin are considering increasing the use of prescribed fire and forest thinning to restore conditions that will be more resilient to wildfires. However, such restorative treatments also constitute disturbances that could increase sediment and nutrient loads. We examined whether the water-quality impacts from future treatments are likely to be lower compared to the potential impacts from future wildfires under various climate change scenarios. We applied an online interface for the Water Erosion Prediction Project (WEPP) model in combination with a landscape change model (LANDIS-II) to evaluate the effects of different combinations of thinning and prescribed burning on fine sediment (< 2 mm), very fine sediment (< 16 µm), and phosphorus over time. First, we generated results based on historic weather data for soil disturbance conditions, including: an undisturbed baseline, a uniform thinning treatment; a uniform prescribed fire treatment; and uniform low, moderate, and high wildfire burn severity. Residual ground cover declined in that order, and expected loads of sediment and phosphorus increased. We then combined the estimated loads from hillslopes with projected management-disturbance regimes across each decade of the next century. We found that expected sediment and phosphorus loads were lower under the scenario that emphasized thinning, whereas scenarios that increased prescribed burning resulted in loads that were comparable to scenarios that involved less treatment. These results reflect the finding from the WEPP analysis that prescribed burning is expected to reduce ground cover more than is thinning. Our analysis supports efforts to increase fuel reduction treatments to mitigate future wildfires, but it also suggests that preventative treatments may not avoid a long-term decline in water quality as wildfires increase with climate change.

Climate change will accelerate forest mortality due to insects, disease, and wildfire. As a result, substantial resources will be necessary where and when forest managers seek to maintain multiple management objectives. Because of the increasing managerial requirements to offset climate change and related disturbances, the uncertainty about future forest conditions is magnified relative to climate change alone. We provide an analytical approach that quantifies the key drivers of forest change—climate, disturbance, and forest management—using scenarios paired with simulation modeling to forecast and quantify uncertainties in the Lake Tahoe Basin of California and Nevada (USA), a montane seasonally dry conifer forest. We partitioned uncertainty among climate change (including associated changes to wildfire and insect outbreaks), forest management (including thinning, prescribed fire, and fire suppression), and other sources using a fully factorial experimental design and analysis of variance. We focused on three metrics that are important for forest management objectives for the area: forest carbon storage, area burned at high severity, and total area burned by wildfire. Management explained a substantial amount of variance in the short term for area burned at high severity and longer term carbon storage, while climate explained the most variance in total area burned. Our results suggest that simulated extensive management activities will not meet all the desired management objectives. Both the extent and intensity of forest management will need to increase significantly to keep pace with predicted climate and wildfire conditions.

Pathology training programs throughout the United States have endured unprecedented challenges dealing with the ongoing coronavirus disease 2019 pandemic. At Houston Methodist Hospital, the Department of Pathology and Genomic Medicine planned and executed a trainee-oriented, stepwise emergency response. The focus was on optimizing workflows among areas of both clinical and anatomic pathology, maintaining an excellent educational experience, and minimizing trainee exposure to coronavirus disease 2019. During the first phase of the response, trainees were divided into 2 groups: one working on-site and the other working remotely. With the progression of the pandemic, all trainees were called back on-site and further redeployed within our department to meet the significantly increased workload demands of our clinical laboratory services. Adjustments to trainee educational activities included, among others, the organization of a daily coronavirus disease 2019 virtual seminar series. This series served to facilitate communication between faculty, laboratory managers, and trainees. Moreover, it became a forum for trainees to provide updates on individual service workflows and volumes, ongoing projects and research, as well as literature reviews on coronavirus disease 2019–related topics. From our program’s experience, redeploying pathology trainees within our department during the coronavirus disease 2019 pandemic resulted in optimization of patient care while ensuring trainee safety, and importantly, helped to maintain continuous high-quality education through active involvement in unique learning opportunities.

Because of past land use changes and changing climate, forests are moving outside of their historical range of variation. As fires become more severe, forest managers are searching for strategies that can restore forest health and reduce fire risk. However, management activities are only one part of a suite of disturbance vectors that shape forest conditions. To account for the range of disturbance intensities and disturbance types (wildfire, bark beetles, and management), we developed a disturbance return interval (DRI) that represents the average return period for any disturbance, human or natural. We applied the DRI to examine forest change in the Lake Tahoe Basin of California and Nevada. We specifically investigated the consequences of DRI on the proportion of high-severity fire and the net sequestration of carbon. In order to test the management component of the DRI, we developed management scenarios with forest managers and stakeholders in the region; these scenarios were integrated into a mechanistic forest landscape model that also accounted for climate change, as well as natural disturbances of wildfire and insect outbreaks. Our results suggest increasing the frequency of disturbances (a lower DRI) would reduce the percentage of high-severity fire on landscape but not the total amount of wildfire in general. However, a higher DRI reduced carbon storage and sequestration, particularly in management strategies that emphasized prescribed fire over hand or mechanical fuel treatments.

Pathological cardiac remodeling during heart failure is associated with higher levels of lipid peroxidation products and lower abundance of several aldehyde detoxification enzymes, including aldehyde dehydrogenase 2 (ALDH2). An emerging idea that could explain these findings concerns the role of electrophilic species in redox signaling, which may be important for adaptive responses to stress or injury. The purpose of this study was to determine whether genetically increasing ALDH2 activity affects pressure overload-induced cardiac dysfunction. Mice subjected to transverse aortic constriction (TAC) for 12 weeks developed myocardial hypertrophy and cardiac dysfunction, which were associated with diminished ALDH2 expression and activity. Cardiac-specific expression of the human ALDH2 gene in mice augmented myocardial ALDH2 activity but did not improve cardiac function in response to pressure overload. After 12 weeks of TAC, ALDH2 transgenic mice had larger hearts than their wild-type littermates and lower capillary density. These findings show that overexpression of ALDH2 augments the hypertrophic response to pressure overload and imply that downregulation of ALDH2 may be an adaptive response to certain forms of cardiac pathology. Keywords: Heart failure, Hypertrophy, Oxidative stress, Aldehydes, Cardiac remodeling, Hormesis

Web cameras are transforming coastal environmental monitoring. Improvements in camera technology and image processing capabilities, paired with decreases in cost, enable widespread use of camera systems by researchers, managers and first responders for a growing range of environmental monitoring applications. Applications are related to transportation and commerce, preparedness, risk reduction and response, and stewardship of coastal resources. While web cameras are seemingly ubiquitous, operators often follow unique installation procedures and collect, store, and process imagery data in various ways. These inconsistencies significantly limit the ability for imagery data to be shared and utilized across research and operational disciplines. Similar to the early days of other remote sensing networks like High Frequency Radar, the benefits and downstream application of coastal imagery data can be greatly enhanced through centralized data access and standardization of data collection, analysis and dissemination. The NOAA National Ocean Service Web Camera Applications Testbed (WebCAT) was launched in 2017 in partnership with SECOORA, as a public-private partnership to address this coastal ocean observing standardization need. WebCAT is a pilot project relying on the private sector expertise of Surfline, Inc., to install and operate several web cameras capable of meeting the short-term needs of diverse users including NOAA, USGS, state health agencies, academia and others. The project aims to determine operational imagery collection, storage, processing, access, and archival requirements that will foster collaboration across research and operational user communities. Seven web cameras have been installed at six locations along the southeast United States coast (from Florida to North Carolina) for purposes including: counting animals on the beach and migrating right whales, identifying rip currents, validating wave runup models, and understanding human use of natural resources. Here we present a review of the state of coastal imagery data and an overview of the WebCAT project. Goals of an upcoming community workshop will also be presented along with our vision for how WebCAT can motivate a future sustained operational web camera network.