bluuebunny/crossref_metadata_2025_split huggingface dataset:
Managing Fall Armyworm in Africa: Can Bt Maize Sustainably Improve Control?
Authors: Van den Berg Johnnie , Prasanna Boddupalli M , Midega Charles A O , Ronald Pamela C , Carrière Yves , Tabashnik Bruce E 
Published: August 2021

Abstract
The recent invasion of Africa by fall armyworm, Spodoptera frugiperda, a lepidopteran pest of maize and other crops, has heightened concerns about food security for millions of smallholder farmers. Maize genetically engineered to produce insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) is a potentially useful tool for controlling fall armyworm and other lepidopteran pests of maize in Africa. In the Americas, however, fall armyworm rapidly evolved practical resistance to maize producing one Bt toxin (Cry1Ab or Cry1Fa). Also, aside from South Africa, Bt maize has not been approved for cultivation in Africa, where stakeholders in each nation will make decisions about its deployment. In the context of Africa, we address maize production and use; fall armyworm distribution, host range, and impact; fall armyworm control tactics other than Bt maize; and strategies to make Bt maize more sustainable and accessible to smallholders. We recommend mandated refuges of non-Bt maize or other non-Bt host plants of at least 50% of total maize hectares for single-toxin Bt maize and 20% for Bt maize producing two or more distinct toxins that are each highly effective against fall armyworm. The smallholder practices of planting more than one maize cultivar and intercropping maize with other fall armyworm host plants could facilitate compliance. We also propose creating and providing smallholder farmers access to Bt maize that produces four distinct Bt toxins encoded by linked genes in a single transgene cassette. Using this novel Bt maize as one component of integrated pest management could sustainably improve control of lepidopteran pests including fall armyworm.
Mass Production of Neoseiulus cucumeris (Acari: Phytoseiidae): An Assessment of 50 Generations Reared on Almond Pollen
Authors: Yazdanpanah Shima , Fathipour Yaghoub , Riahi Elham , Zalucki Myron P 
Published: August 2021

Abstract
Neoseiulus cucumeris (Oudemans) (Acari: Phytoseiidae), an economically important biocontrol agent, was reared on almond pollen for 50 generations. We evaluated the effect of rearing predators on this pollen by comparing biological parameters at different generations (G1–G50). The shortest and longest development time occurred in G5 and G10, respectively. Females at the fifth and 50th generations laid eggs earlier than those of other generations. Females at G50 laid eggs over a longer period and produced more eggs than females of other generations, although females in the earlier generations had a higher gross reproductive rate and net reproductive rate than later generations. The intrinsic rate of increase, as well as the finite rate of increase of N. cucumeris in the fifth and 50th generations was significantly greater than those in other generations, while the first generation had the lowest values of these parameters. The dorsal shield length of both females and males and the width of females were found to be unaffected by their constant feeding on almond pollen. However, the number of rearing generations significantly affected the width of males. Long-term rearing of N. cucumeris for at least 50 generation on almond pollen did not substantially affect the predator's quality and this food source could be used for the mass production of this predator. Almond pollen should be assessed in rearing other phytoseiid mites that are important in biocontrol strategies.
Risk Assessment of Ozone Fumigation Under Vacuum to Control Potential Infestation of Coffee Berry Borer and Coffee Leaf Rust in Green Coffee Beans Imported Into Hawaii
Authors: Portilla M , Follett P A , Armstrong J W , Leesch J G , Tebbets J S , Smilanick J , McHugh T H , Olsen C W , Whitehand L , Cavaletto C , Bittenbender H C S , Bustillo A E , Peña J E 
Published: August 2021

AbstractStudies were conducted with ozone gas fumigation under vacuum as a methyl bromide alternative against life stages of coffee berry borer (CBB) Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae: Scolytinae), and the urediniospores of coffee leaf rust (CLR), Hemileia vastatrix Berkeley & Broome (Basidiomycota: Pucciniales) in green coffee, Coffea spp. L. Fumigation with 10,000 ppm O3 gas under −25.4 mm Hg vacuum1 at 13.0 ± 3.0°C for 6.0 h killed all CBB larvae, pupae, and adults, but did not kill all CBB eggs (~15% survival). Mortality of CLR urediniospores was 100% within the first hour of the 6-h fumigation. Ozone fumigation had no adverse effects on coffee quality. Results indicated that CBB adult hitchhikers may be the only target life stage of quarantine concern, and additional studies focused on this stage. CBB adult survival and reproduction decreased significantly at moisture contents ≤20%, and F1 generation survival did not occur in green coffee at moisture contents ≤15%. As the international standard for green coffee moisture content is 9–12%, adult CBB should not survive or reproduce in exported dry green coffee. Standard industry processing of harvested coffee cherries to the green coffee stage using either mechanical- or sun-drying eliminated CBB infestations from the field. A systems approach is recommended for exporting green coffee to control CBB and CLR that includes eliminating CBB life stages with standard processing methods, reducing moisture content to 9–12% to prevent egg deposition, survival or reproduction, and O3 fumigation to ensure quarantine security against potential CBB adult hitchhikers.
Novel Methods for Detecting Human Cholesterol Crystals from Sampled Blood
Authors: Iwa Nobuzo , Yutani Chikao , Komatsu Sei , Takahashi Satoru , Takewa Mitsuhiko , Ohara Tomoki , Kodama Kazuhisa 
Published: August 2021

Abstract

Objective
Nonobstructive general angiography (NOGA) is a novel modality to detect and sample spontaneous ruptured aortic plaques (SRAPs). We aimed to establish novel methods to detect cholesterol crystals (CCs) in sampled SRAPs.

Methods
Blood specimens containing SRAPs were obtained from patients using NOGA. Blood was instantly frozen on a glass slide and subsequently thawed for quantitative analysis and spread onto a filter paper that was rinsed using distilled water. Qualitative analysis was performed for the rinsed water using polarized light microscopy, and the filter paper was embedded in paraffin for histologic analysis.

Results
The CCs were clearly observed after hemolysis using the instant freeze-thaw method. The filter paper rinse method indicated free CCs of varying shapes under polarized light microscopy without erythrocytes. On the filter paper, sampled SRAPs showed Lamé-like small particles. Histopathology revealed various atheromatous components.

Conclusion
A set of novel methods for detecting CCs from sampled blood was established.
BSCI-03. Adaptation of colorectal cancer cells to the brain microenvironment: The role of IRS2
Authors: Greenberg Inbal , Klein Anat , Grossman Rachel , Sokol Ethan , Yeini Eilam , Ofek Paula , Satchi-Fainaro Ronit , Liang Bertrand , Reuveni Hadas , Rubinek Tami , Wolf Ido 
Published: August 2021

Abstract
Colorectal cancer (CRC) reflects the fourth most frequent etiology of brain metastasis (BM). Yet, molecular mechanisms supporting it are unknown. We aimed to explore drivers enabling adaptation of CRC cells to the brain and decipher mechanisms facilitating the process.
We analyzed the FoundationOne database, which contains genomic alterations data of cancer-related genes in over 16,000 human CRC primary and metastasis samples. Increased prevalence of IRS2 gene amplification was observed in 13% of BM, compared to only 3% of primary tumors or other metastatic sites. IRS2 is a cytoplasmic adaptor mediating effects of insulin and IGF-1 receptors and is involved in more aggressive behavior of different cancer types. In agreement with the genomic data, immunohistochemistry of human clinical samples showed increased expression of IRS2 protein in BM. We constructed an in-vitro system mimicking the brain microenvironment using cultured human astrocytes or their conditioned media. Under these conditions, IRS2-overexpressed CRC cells survived better and formed larger 3D spheres. IRS2-silenced CRC cells showed a mirror image. Moreover, in an intracranial CRC BM mouse model, IRS2-overexpressed cells generated larger brain lesions, while silencing IRS2 dramatically decreased tumor outgrowth and extended survival. Interestingly, transcriptomic analysis revealed enrichment of oxidative phosphorylation (OXPHOS) and Wnt/β-catenin pathways by IRS2. Indeed, IRS2-expressing cells showed increased mitochondrial activity and glycolysis-independent viability. Furthermore, IRS2-expressing cells had increased β-catenin transcriptional activity. Interestingly, β-catenin or IRS2 inhibition (using NT219) in IRS2-expressing cells decreased their viability, β-catenin transcriptional activity, and OXPHOS gene expression, suggesting involvement of IRS2 in modulating OXPHOS through β-catenin. β-catenin is known to confer 5-FU resistance; consequently, we showed that combination of 5-FU and NT219 worked in synergy, inhibited the formation of BM, and extended animal survival.
These data reveal the unique genomic profile of CRC BM and suggest IRS2 inhibition as a novel target for treatment of these patients.
BSCI-06. Phage display biopanning identifies Amot regulating cell motility in brain metastasis-initiating cells
Authors: She Chunhua , Potez Marine , Kim JongMyung , Liu James 
Published: August 2021

Abstract

Objective
Metastatic brain tumors (MBTs) are the most common type of malignant brain tumors. Due to the deviation of MBTs from the parental tumors, the effective therapies for primary tumors often are not working in brain metastases. Even more new intracranial lesions were developed though the primary lesion was controlled. The occurrence of brain metastasis-initiating cells (BMICs) suggested the possibility of its spread intracranially. Here we aimed to explore the biological behavior in cell motility of BMICs and understand the potential mechanisms.

Methods
In vitro and in vivo phage display biopanning strategies were used to isolate dodecapeptides that specifically target BMICs by selecting against primary lung cancer cells and normal brain cells. In silico analysis was used to derive specific protein targets in BMICs. Potential targets were narrowed down through analysis in patient databases and verified for their presence in BMIC through RT-PCR. Cell migration and adhesion in BMICs were analyzed using Transwell, scratch, and adhesion assays. Protein expression and cell morphology were detected by immunofluorescence. Immune blot was performed to detect the epithelial-mesenchymal related molecules and explore protein-protein interactions.

Results
In silico analysis of BMICs specific peptides revealed Angiomotin (Amot) as a potential target in BMICs. Amot was found to be overexpressed in BMICs compared to primary lung cancer cells. Kaplan-Meier analysis demonstrated Amot was negatively correlated with overall survival among lung adenocarcinoma patients. Knockdown of AMOT in BMICs decreased the capability of cell migration and adhesion, through the downregulation of E-Cadherin. Amot was found to maintain the E-Cadherin in BMICs through reducing ubiquitination of E-Cadherin. Furthermore, the knockdown of E-Cadherin decreased cell migration and adhesion due to the decrease in cdc42 activity.

Conclusions
Amot plays a role in promoting migration and adhesion in BMICs through preservation of E-Cadherin.
BSCI-16. Olfactory receptor 5B21 drives breast cancer metastasis
Authors: Li Mao , Schweiger Markus , Nakano Ichiro , Ryan Daniel , Carvalho Litia , Tannous Bakhos 
Published: August 2021

Abstract
Olfactory receptors (ORs), responsible for the sense of smell, play an essential role in physiological processes (even outside the nasal epithelium) and cancer. In breast cancer, however, the expression and role of ORs remain understudied. We examined the significance of ORs transcript abundance in breast cancer metastasis to different tissues including the brain, bone, and lung. While we found 20 OR genes to be differentially expressed in different metastasis versus primary tumor, OR5B21 displayed high relation with all metastases. Knockdown of OR5B21 significantly decreased the invasion and migration of breast cancer cells in culture as well as metastasis to different organs including the brain, in vivo. On the other hand, overexpression of OR5B21 in the primary cells had the opposite effect. Mechanistically, OR5B21 was associated with epithelial to mesenchymal transition through STAT3/NFkB/CEBPβ signaling pathway. We propose OR5B21 (and potentially other ORs) as a novel oncogene contributing to breast cancer metastasis, and as a potential target for therapy.
BSCI-17. Targeting SIRPα as a therapeutic strategy for the treatment of breast cancer brain metastasis
Authors: Stirling Elizabeth R , Bronson Steven M , Crowe William N , Wilson Adam , Kooshki Mitra , Zhao Dawen , Triozzi Pierre L , Lesser Glenn J , Soto-Pantoja David R 
Published: August 2021

Abstract
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer characterized by the lack of druggable targets and an incidence of brain metastasis from the primary site of approximately 35%. There is no standard treatment for managing brain metastasis associated with TNBC; therefore, new strategies are urgently needed to overcome disease mortality. The CD47/SIRPα signaling pathway is implicated in tumor progression due to bypassing innate and adaptive immune surveillance. Most strategies targeting this pathway focus on targeting the receptor CD47; however, targeting SIRPα as a potential strategy to mitigate tumor burden remains understudied. Analysis of gene expression database shows that SIRPα expression is significantly elevated in invasive breast cancer when compared to primary. Furthermore, single-cell data indicates that SIRPα is expressed in basal epithelial cells in TNBC tumors aside from the myeloid compartment. Our immune staining against SIRPα in patient biopsies shows a five-fold increase in SIRPα expression in metastatic brain tumors compared to the primary lesions. Therefore, targeting SIRPα may be a new immunotherapeutic strategy to treat breast cancer brain metastases. Anti-SIRPα treatment of mice bearing brain metastatic 4T1br3 orthotopic tumors showed reduced tumor volume and tumor weight by over 50% compared to isotype control-treated mice. Furthermore, in a model of intracardial brain metastasis, treatment with SIRPα antibody was associated with a 60% increase in survival compared to isotype control-treated mice. RNA sequencing of tumors indicated that SIRPα blockade is associated with a reduction in genes linked to mitochondrial respiratory chain and increases in negative regulation of the cell cycle. Furthermore, in vitro SIRPα targeting enhanced the cell-mediated cytotoxicity of microglia against 4T1Br3 breast cancer cells. This suggests that SIRPα blockade may influence both tumor and innate immune cells to limit brain metastatic breast cancer growth and enhance survival.
BSCI-18. Identifying novel drivers of lung-to-brain metastasis through in vivo functional genomics
Authors: Aghaei Nikoo , Lam Fred C , Kasper Ekkehard , Venugopal Chitra , Singh Sheila 
Published: August 2021

Abstract

Introduction
Brain metastases, the most common tumors of the central nervous system, occur in approximately 20% of primary adult cancers. In particular, 40% of patients with non-small cell lung cancer develop brain metastasis. As systemic therapies for the treatment of non-small cell lung cancer become increasingly effective at controlling primary disease, patients are ironically succumbing to their brain metastases. This highlights a large unmet need to develop novel targeted therapies for the treatment of lung-to-brain metastases (LBM). We hypothesize that an in vivo functional genomic screen can identify novel genes that drive LBM.

Methods
To do this, we developed a patient-derived xenograft (PDX) mouse model of LBM using patient lung cancer cell lines. This PDX model of LBM enables the use of fluorescent and bioluminescent in vivo imaging to track the progression of lung tumor and brain metastases.

Results
We have performed an in vivo genome-wide CRISPR activation screening to identify novel drivers of LBM. We will derive candidate genes through mouse brain and lung tissue sequencing after mice reach endpoint.

Expected Area of findings
This platform will lead to potential therapeutic targets to prevent the formation of LBM and prolong the survival of patients with non-small cell lung cancer.

Limitations
There may be limitations in getting candidate hits that overlap in all mice in our first replicate. This can be remedied by conducting the in vivo screen in at least three biological replicates.

Conclusion
To the best of our knowledge, this is the first genome-wide in vivo CRISPR activation screen searching for drivers of LBM using a PDX animal model. This study can provide a framework to gain a deeper understanding of the regulators of BM formation which will hopefully lead to targeted drug discovery.
TRLS-05. A multicenter observational study of Cs-131 seeds embedded in a collagen carrier tile for newly diagnosed and recurrent operable intracranial neoplasms –Trial in progress
Authors: Dunbar Erin , McCracken D Jay , Nowlan Adam , Chen Clark , Dusenbery Kathryn , Ferreira Clara , Kotecha Rupesh , McDermott Michael , Jaikumar Sivakumar , Shen Colette , Monyak David , Trusheim John , Wanebo John , Day Samuel , Lee Stuart , Wardak Zabi , Patel Toral , Choi Mehee , Misell Lisa , Brachman David 
Published: August 2021

Abstract

Background
For patients with operable intracranial neoplasms, there are opportunities to augment local control beyond traditional methods, such as external beam radiation therapy (EBRT),. Brachytherapy, the implantation of radioactive sources into the resection cavity, can be useful in this setting by providing immediate initiation of radiation and limiting the exposure of surrounding normal tissue to radiation. Traditional intracranial brachytherapy methods have been limited by uneven dose distributions, complicated workflows, extended procedural times, the cost of dedicated equipment, and frequent adverse events. To address these issues, a permanently implanted device with Cs-131 radiation seeds embedded in a bioresorbable collagen carrier tile (GammaTile, GT Medical Technologies, Tempe, AZ USA) was developed. Described as surgically targeted radiation therapy (STaRT), it is FDA-cleared for use in newly-diagnosed malignant intracranial neoplasms and recurrent intracranial tumors, including brain metastases, and has demonstrated excellent safety and local control in early commercial use. The primary objectives of this multicenter, prospective, observational (phase IV) registry study [NCT04427384] are to evaluate “real-world” clinical outcomes and patient-reported outcomes that measure the safety and efficacy of STaRT using the device.

Methods
Subjects (N=600) at up to 50 enrolling sites undergoing resection of brain tumors of any pathology with intra-operative GammaTile placement are eligible for enrollment. We project 40% of enrollees to have brain metastasis. Tumor pathology, overall survival, radiation- and surgery-related adverse events, quality of life, serial MRIs, and timing of surgical bed recurrence and/or distant recurrence will be collected. The powered primary endpoint for recurrent brain metastases, surgical bed-progression free survival, will compare STaRT to standard-of-care benchmarks. This study will be the first observational study of resection plus GammaTile. Results will be used to benchmark clinical outcomes in the real-world setting, allow for comparisons to existing treatments, and facilitate the design of future clinical trials.
LMD-01. Quantifying intrathecal drug delivery utilizing programmable ventriculoperitoneal shunts
Authors: McThenia Sheila , Pandit-Taskar Neeta , Grkovski Milan , Donzelli Maria , Diagana Safiatu , Greenfield Jeffrey , Souweidane Mark , Kramer Kim 
Published: August 2021

Abstract

Background
Programmable ventriculoperitoneal shunts (pVP shunts) are increasingly utilized for intraventricular chemotherapy, radioimmunotherapy, and/or cellular therapy. Shunt adjustments allow optimization of thecal space drug concentrations with minimization in the peritoneum. Drug delivery quantification using several types of pVP shunts has not been reported.

Methods
We performed a retrospective analysis on patients with CNS tumors and pVP shunts at Memorial Sloan Kettering Cancer Center from 2003–2020, noting shunt model. CSF flow through the pVP shunt was evaluated using In-111-DTPA scintigraphy at approximately 4 and 24 hours after injection. pVP shunts were calibrated pre-injection to minimize peritoneal flow and re-calibrated to baseline setting 4–5 hours following injection. Scintigraphy studies quantified ventricular-thecal and peritoneal drug activity at these 2 time points.

Results
Twenty-one CSF flow studies were administered to 15 patients, ages 1–27 years. Diagnoses included medulloblastoma (N=10), metastatic neuroblastoma (N=3), pineoblastoma (N=1), and choroid plexus carcinoma (N=1). Models of pVP shunts included Aesculap Miethke proGAV (N=3), Aesculap Miethke proGAV2.0 (N=3), Codman HAKIM (N=2), Codman Certas Plus (N=1), Medtronic STRATA (N= 5), and Sophysa Polaris (N= 1). All 21 studies (100%) demonstrated ventriculo-thecal drug activity. 29% (6 of 21) of the studies had no peritoneal uptake visible by imaging. 73% (16 of 21) of the studies had minimal peritoneal uptake (&lt;12%), and 24% (5 of 21) demonstrated moderate peritoneal uptake (12–37%). Models of pVP shunts measuring minimal to no peritoneal uptake included: Aesculap Miethke proGAV (N=2), Aesculap Miethke proGAV2.0 (N=3), Codman HAKIM (N=2), Codman Certas Plus (N=1), Medtronic STRATA (N= 3), and Sophysa Polaris (N= 1).

Conclusions
pVP shunts successfully deliver drugs to the ventriculo-thecal space with 80% of studies having minimal (&lt;12%) peritoneal drug activity. Though efficacy varies by shunt model, low numbers preclude conclusions regarding model superiority. CSF flow scintigraphy studies reliably assess drug distribution.